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  • 51.
    Byström, Per
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Johansson, Birgitta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Berglund, Åke
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Sorbye, H
    Tveit, KM
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Health-related quality of life in patients with metastatic colorectal cancer receiving palliative combination chemotherapy2012Artikkel i tidsskrift (Fagfellevurdert)
  • 52.
    Börjeson, Sussanne
    et al.
    Linköpings universitet.
    Johansson, Birgitta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Omvårdnad vid cytostatikabehandling2011Inngår i: Omvårdnad vid bröstcancer: nationellt vårdprogram 2011: giltighetstid 2011-2012 / [ed] Ledningsgruppen sjuksköterskor i bröstcancervården, Stockholm: Onkologiskt Centrum Stockholm-Gotlandregionen , 2011, 2. uppl., s. 34-40Kapittel i bok, del av antologi (Annet (populærvitenskap, debatt, mm))
  • 53.
    Börjeson, Sussanne
    et al.
    Linköpings universitet.
    Johansson, Birgitta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Psykosocial onkologi och stödjande vård.
    Onkologisk omvårdnad2008Inngår i: Onkologi / [ed] Ulrik Ringborg, Roger Henriksson & Tina Dalianis, Stockholm: Liber, 2008, 2. uppl., s. 232-242Kapittel i bok, del av antologi (Annet vitenskapelig)
  • 54.
    Cashin, Peter H
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Ehrsson, H
    Wallin, I
    Nygren, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Mahteme, Haile
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Pharmacokinetics of cisplatin during hyperthermic intraperitoneal treatment of peritoneal carcinomatosis2013Inngår i: European Journal of Clinical Pharmacology, ISSN 0031-6970, E-ISSN 1432-1041, Vol. 69, nr 3, s. 533-540Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose

    Cisplatin during hyperthermic intraperitoneal chemotherapy (HIPEC) has not previously been measured with a selective technique. The primary aims were to examine the pharmacokinetics of active cisplatin and its monohydrated complex (MHC) during HIPEC using a specific measuring technique, to compare cisplatin’s systemic absorption with oxaliplatin, and to compare active cisplatin levels to that of total platinum.

    Methods

    Ten patients treated with cytoreductive surgery and HIPEC (cisplatin 50 mg/m2,doxorubicin 15 mg/m2) were recruited. Blood and perfusate samples were drawn during and after HIPEC. Cisplatin analysis was conducted using liquid chromatography (LC) with post-column derivatization with diethyldithiocarbamate and compared with inductively coupled plasma-mass spectrometry (ICP-MS).

    Results

    The mean half-life (t1/2) of perfusate cisplatin was 18.4 min, with area under the time-concentration curve (AUC) 0–90 min of 2.87 mM·min and estimated 0–60 min of 2.45 mM·min. The absorption t1/2 was 9.0 min for cisplatin and 18.2 min for oxaliplatin. The ratio of total platinum to active cisplatin increased in a linear manner by time of perfusion.

    Conclusions

    Cisplatin is absorbed quicker than oxaliplatin. Lowering the perfusion time to 60 min does not significantly change the pharmacokinetics of cisplatin, and is therefore to be considered. As the HIPEC perfusion progresses, the ICP-MS technique does not adequately reflect active cisplatin levels in the perfusate

  • 55.
    Cashin, Peter H.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Graf, Wilhelm
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Nygren, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Mahteme, Haile
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Comparison of Prognostic Scores for Patients with Colorectal Cancer Peritoneal Metastases Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy2013Inngår i: Annals of Surgical Oncology, ISSN 1068-9265, E-ISSN 1534-4681, Vol. 20, nr 13, s. 4183-4189Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background. There are three prognostic scores for the cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) treatment of colorectal cancer peritoneal metastases: the newly introduced COREP (colorectal peritoneal) score, the peritoneal surface disease severity score (PSDS), and the prognostic score (PS). The aim was to determine which prognostic score had the best prognostic value. Methods. Between 2006 and 2010, a total of 77 patients with peritoneal metastases fromcolorectal cancer underwent CRS/HIPEC treatment. The COREP, PSDS, and PS scores were successfully applied to 56 patients (73 %) having sufficient data. The end points were prediction of open-and-close cases (n = 9), R1 resections (n = 41), and survival of <12 months (n = 18). Area under the receiver operating characteristic curves (accuracy) was compared. Subgroup analysis was performed on patients not previously used for the development of the COREP score (n = 24). Multivariable logistic regressions of the three end points were performed as well as Cox regression for overall survival. Furthermore, COREP and peritoneal cancer index were compared. Results. For open-and-close case prediction, accuracy for the whole group (n = 56) and subgroup (n = 24) was 87 and 88 %, respectively for COREP; 66 and 77 % for PSDS; and 68 and 78 % for PS. For R1 resection prediction, accuracy was 81 and 81 %, 76 and 78 %, and 75 and 77 %, respectively. For prediction of survival of <12 months, accuracy was 83 and 84, 54 and 67 %, and 55 and 56 %, respectively. The COREP score was the only independent prognostic factor in all four multivariable analyses. A COREP score of >= 6 identified patients with poor survival more accurately than a PCI of >20. Conclusions. The COREP score predicted open-and-close cases, R1 resections, and poor survival better than PSDS and PS. COREP better identifies patients with poor survival than intraoperative PCI.

  • 56.
    Cashin, Peter H
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Graf, Wilhelm
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Nygren, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Mahteme, Haile
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Cytoreductive Surgery and Intraperitoneal Chemotherapy for Colorectal Peritoneal Carcinomatosis: Prognosis and Treatment of Recurrences in a Cohort Study2012Inngår i: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 38, nr 6, s. 509-515Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background

    Cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC) treatment of colorectal peritoneal carcinomatosis (PC) is gaining acceptance, but controversy remains. The primary aims were to analyze the outcome and prognostic variables of colorectal PC patients treated with CRS and IPC, and to report on the outcome of additional surgical treatments of subsequent recurrences.

    Methods

    Patients referred for treatment of colorectal PC between 1996 and 2010 were included in a cohort. The following data was collected: clinicopathological parameters, survival, recurrences, perioperative chemotherapy and type of IPC (hyperthermic intraperitoneal chemotherapy, HIPEC; or sequential postoperative intraperitoneal chemotherapy, SPIC). Multivariable analyses were conducted on potential prognostic factors for overall survival (OS).

    Results

    In the 151-patient cohort, the median OS was 34months (range: 2-77) for CRS and HIPEC with five-year survival predicted at 40% (five-year disease-free survival 32%). For CRS and SPIC, the OS was 25months (range: 2-188) with five-year survival at 18%.  Open-and-close patients survived 6months (range: 0-14) with no five-year survival (HIPEC vs. SPIC p=0.047, SPIC vs. open-and-close p<0.001). Adjuvant systemic chemotherapy was a noteworthy independent prognostic factor in the multivariable analysis. OS for patients undergoing additional surgical treatment of recurrences was 25months vs. 10months with best supportive care or palliative chemotherapy (p=0.01).

    Conclusion

    Substantial long-term survival is possible in patients with colorectal PC. HIPEC was associated with better OS than SPIC and adjuvant systemic chemotherapy may improve the outcome in patients. Good OS is achievable in selected patients undergoing additional surgical treatment of isolated liver or peritoneal recurrences after prior complete CRS.

  • 57.
    Cashin, Peter H
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Graf, Wilhelm
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Nygren, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Mahteme, Haile
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Intraoperative hyperthermic versus postoperative normothermic intraperitoneal chemotherapy for colonic peritoneal carcinomatosis: a case-control study2012Inngår i: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 23, nr 3, s. 647-652Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND:

    Cytoreductive surgery and intraperitoneal chemotherapy has improved prognosis in patients with peritoneal carcinomatosis. The main modes of intraperitoneal chemotherapy treatment are peroperative hyperthermic intraperitoneal chemotherapy (HIPEC) and normothermic sequential postoperative intraperitoneal chemotherapy (SPIC). The aim of this study was to compare HIPEC and SPIC with respect to overall survival, disease-free survival, morbidity, and mortality in patients with peritoneal carcinomatosis from colon cancer.

    PATIENTS AND METHODS:

    A matched case-control study was conducted in patients with surgical macroscopic complete removal of carcinomatosis; matching was according to the peritoneal cancer index score. Thirty-two patients were included, 16 in each group (HIPEC and SPIC). Overall survival, disease-free survival, morbidity, mortality, and clinicopathological parameters were compared.

    RESULTS:

    Median overall survival was 36.5 months in the HIPEC group and 23.9 months in the SPIC group (P = 0.01). Median disease-free survival for these groups was 22.8 (HIPEC) and 13.0 months (SPIC; P = 0.02). Morbidity was not statistically different, 19% in SPIC and 37% in HIPEC. Postoperative mortality was observed in one patient in each group.

    CONCLUSION:

    HIPEC was associated with improved overall survival and disease-free survival compared with SPIC at similar morbidity and mortality, suggesting that HIPEC is the treatment of choice in colonic peritoneal carcinomatosis.

  • 58.
    Cashin, Peter H
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Graf, Wilhelm
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Nygren, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Mahteme, Haile
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Patient Selection for Cytoreductive Surgery in Colorectal Peritoneal Carcinomatosis using Serum Tumour Markers – an Observational Cohort Study2012Inngår i: Annals of Surgery, ISSN 0003-4932, E-ISSN 1528-1140, Vol. 256, nr 6, s. 1078-1083Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: There were 2 objectives: first, to investigate how many patients were excluded from surgery on the basis of the radiological extent of the peritoneal carcinomatosis (PC) or the clinical examination; and second, to develop a score based primarily on serum tumor markers (STMs) that could predict short cancer-specific survival (<12 months). Background: Patient selection and prediction of prognosis is crucial for successful treatment of colorectal PC. Methods: All patients with colorectal PC referred for cytoreductive surgery and intraperitoneal chemotherapy (2005-2008) at Uppsala University hospital were included. Patients were divided into 2 groups-nonsurgery and surgery. Clinicopathological and laboratory parameters were collected in the surgery group. A Corep (COloREctal-Pc) score was developed using hazard ratios from histology, hematological status, serial serum tumor markers (STMs), and STM changes over time. Sensitivity, specificity, positive predicted value (PPV), and negative predicted value (NPV) were calculated in a second validating dataset (n = 24) with a survival cutoff of less than 12 months. Results: A total of 107 patients were included in the study, 42 in the nonsurgery group and 65 in the surgery group. In the nonsurgery group, 2 patients were excluded solely on the basis of the radiological extent of PC and 7 patients on clinical examination. The Corep score ranged from 0 to 18. A score of 6 or more showed a validated sensitivity of 80%, specificity 100%, PPV 1.0, and NPV 0.93. Conclusions: Radiological extent of PC was not a main deciding factor for treatment decisions and had less impact than the clinical examination. The Corep score identified patients with short cancer-specific survival that may not be suitable for treatment.

  • 59.
    Cashin, Peter H.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Graf, Wilhelm
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Nygren, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Mahteme, Haile
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Response to comments on 'Cytoreductive surgery and intraperitoneal chemotherapy'2012Inngår i: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 38, nr 10, s. 1012-1012Artikkel i tidsskrift (Fagfellevurdert)
  • 60.
    Cashin, Peter H
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Mahteme, Haile
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Graf, Wilhelm
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Karlsson, Henning
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakologi.
    Larsson, Rolf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakologi.
    Nygren, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Activity ex vivo of cytotoxic drugs in patient samples of peritoneal carcinomatosis with special focus on colorectal cancer2013Inngår i: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 13, s. 435-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: The optimal choice of cytotoxic drugs for intraperitoneal chemotherapy (IPC) in conjunction with cytoreductive surgery (CRS) for treatment of peritoneal carcinomatosis(PC) is poorly defined. We investigated drug sensitivity ex vivo in patient samples of various PC tumor types and correlated clinical outcome to drug sensitivity within the subset of PC fromcolorectal cancer (CRC). 

    Methods: PC tissue samples (n = 174) from mesothelioma, pseudomyxoma peritonei (PMP), ovarian cancer, CRC or appendix cancer were analyzed ex vivo for sensitivity to oxaliplatin, cisplatin, mitomycin C, melphalan, irinotecan, docetaxel, doxorubicin and 5-FU. Clinicopathological variables and outcome data were collected for the CRC subset. 

    Results: Mesothelioma and ovarian cancer were generally more drug sensitive than CRC, appendix cancer and PMP. Oxaliplatin showed the most favorable ratio between achievable IPC concentration and ex vivo drug sensitivity. Drug sensitivity in CRC varied considerably between individual samples. Ex vivo drug sensitivity did not obviously correlate to time-to-progression (TTP) in individual patients. 

    Conclusions: Drug-sensitivity varies considerably between PC diagnoses and individual patients arguing for individualized therapy in IPC rather than standard diagnosis-specific therapy. However, in the current paradigm of treatment according to diagnosis, oxaliplatin is seemingly the preferred drug for IPC from a drug sensitivity and concentration perspective. Inthe CRC subset, analysis of correlation between ex vivo drug sensitivity and TTP was inconclusive due to the heterogeneous nature of the data.

  • 61.
    Cashin, Peter
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Nygren, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Hellman, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Granberg, Dan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Andréasson, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Mahteme, Haile
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Appendiceal Adenocarcinoids with Peritoneal Carcinomatosis Treated with Cytoreductive Surgery and Intraperitoneal Chemotherapy: a retrospective study of in vitro drug sensitivity and survival2011Inngår i: Clinical Colorectal Cancer, ISSN 1533-0028, Vol. 10, nr 2, s. 108-112Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose: The purpose of this study was to present results on cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) of appendiceal adenocarcinoid (MC) with peritoneal carcinomatosis (PC), to assess drug sensitivity of AAC, as compared with colorectal cancer (CRC), and to report any discordant histopathology.

    Methods: Ten patients were treated with CRS and HIPEC. Treatment, drug sensitivity profiles, histopathology, and survival data were recorded and matched with potential prognostic indicators. Drug sensitivity was assessed with short-term fluorometric microculture cytotoxicity assay and compared with peritoneal metastases from CRC.

    Results: Patients with completeness of cytoreduction score (CC) 1 (16.4 months). In the CC 1 group. For standard drugs, tumor cells from MC and CRC were equally sensitive; except for docetaxel, to which MC was more sensitive than CRC.

    Conclusion: The CC-score correlated with overall survival. Candidates for this type of treatment should be referred early for evaluation in order to reach a better CC score. Drugs used for CRC also seem adequate for treatment of MC, although other drugs, eg, docetaxel, might be more active.

  • 62.
    Cavalli-Björkman, Nina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Factors Influencing Selection of Treatment for Colorectal Cancer Patients2012Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    In Sweden and elsewhere there is evidence of poorer cancer survival for patients of low socioeconomic status (SES), and in some settings differences in treatment by SES have been shown.

    The aim of this thesis was to explore factors which influence cancer treatment decisions, such as knowledge reaped from clinical trials, patient-related factors, and physician-related factors. In a register study of colorectal cancer, all stages, patients were stratified for SES-factors. Differences were seen with regards to clinical investigation, surgical and oncological treatment and survival, with the highly educated group being favored. Survival was better for highly educated patients in stages I, II and III but not in stage IV.

    In a Scandinavian cohort of newly metastasized colorectal cancer patients, recruitment to clinical trials was studied. Patients entering clinical trials had better performance status and fewer cancer symptoms than those who were treated with chemotherapy outside of a clinical trial. Median survival was 21.3 months for trial-patients and 15.2 months for those treated with chemotherapy outside a  trial. Those not treated with chemotherapy had a median survival of just 2.1 months. Patients in clinical trials are highly selected and conclusions drawn from studies cannot be applied to all patients.

    In the same cohort, treatment and survival were stratified for education, smoking and indicators of social structure. Highly educated patients did not have a survival advantage. Patients who lived alone were offered less combination chemotherapy and surgery of metastases than other patients and had 4 months shorter survival than those who lived with a spouse or child. In a fourth study, 20 Swedish gastrointestinal oncologists were interviewed on which factors they considered when deciding on oncological treatment. Oncologists feared chemotherapy complications due to lack of social support, and ordered less combination chemotherapy for patients living alone. Highly educated patients were seen as well-read and demanding, and giving in to these patients’ requests for treatment was regarded as a way of pleasing patients and relatives and of avoiding conflict.

    Delarbeid
    1.
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    2. Clinical trial enrollment, patient characteristics, and survival differences in prospectively registered metastatic colorectal cancer patients
    Åpne denne publikasjonen i ny fane eller vindu >>Clinical trial enrollment, patient characteristics, and survival differences in prospectively registered metastatic colorectal cancer patients
    Vise andre…
    2009 (engelsk)Inngår i: Cancer, ISSN 0008-543X, E-ISSN 1097-0142, Vol. 115, nr 20, s. 4679-87Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    BACKGROUND: Trial accrual patterns were examined to determine whether metastatic colorectal cancer (mCRC) patients enrolled in trials are representative of a general cancer population concerning patient characteristics and survival.

    METHODS: A total of 760 mCRC patients referred for their first oncological consideration at 3 hospitals in Scandinavia covering defined populations were registered consecutively during 2003 to 2006. Clinical trial enrollment, patient characteristics, and treatment were recorded prospectively, and the follow-up was complete.

    RESULTS: Palliative chemotherapy was initiated in 61% of the patients. Approximately one-third (36%) of patients receiving chemotherapy were included in a trial. The main reason for nonparticipation was failed eligibility criteria (69%). The median survival after chemotherapy was 15.8 months for all patients, and 18 months after combination chemotherapy. Trial patients had better prognostic characteristics and significantly longer survival than nontrial patients: 21.3 months versus 15.2 months when receiving combination chemotherapy. Poor performance status was the main reason for giving best supportive care only, and the median survival was then only 2.1 months. The median survival for all 760 nonresectable mCRC patients was 10.7 months.

    CONCLUSIONS: mCRC patients enrolled into clinical trials differ in characteristics from patients receiving chemotherapy outside protocol and have better survival, even when given the same treatment. Although trial patients have a median survival close to 2 years, survival is lower for all patients receiving chemotherapy and much lower for all patients diagnosed with mCRC. Studies that better accept the heterogeneity of the population with mCRC are needed.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-113895 (URN)10.1002/cncr.24527 (DOI)000270740900007 ()19562777 (PubMedID)
    Tilgjengelig fra: 2010-02-04 Laget: 2010-02-04 Sist oppdatert: 2017-12-12bibliografisk kontrollert
    3. Lower treatment intensity and poorer survival in metastatic colorectal cancer patients who live alone
    Åpne denne publikasjonen i ny fane eller vindu >>Lower treatment intensity and poorer survival in metastatic colorectal cancer patients who live alone
    Vise andre…
    2012 (engelsk)Inngår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 107, nr 1, s. 189-194Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    BACKGROUND: Socioeconomic status (SES) and social support influences cancer survival. If SES and social support affects cancer treatment has not been thoroughly explored. METHODS: A cohort consisting of all patients who were initially diagnosed with or who developed metastatic colorectal cancer (mCRC, n = 781) in three Scandinavian university hospitals from October 2003 to August 2006 was set up. Clinical and socioeconomic data were registered prospectively. RESULTS: Patients living alone more often had synchronous metastases at presentation and were less often treated with combination chemotherapy than those cohabitating (HR 0.19, 95% CI 0.04-0.85, P = 0.03). Surgical removal of metastases was less common in patients living alone (HR 0.29, 95% CI 0.10-0.86, P = 0.02) but more common among university-educated patients (HR 2.22, 95% CI 1.10-4.49, P = 0.02). Smoking, being married and having children did not influence treatment or survival. Median survival was 7.7 months in patients living alone and 11.7 months in patients living with someone (P < 0.001). Living alone remained a prognostic factor for survival after correction for age and comorbidity. CONCLUSION: Patients living alone received less combination chemotherapy and less secondary surgery. Living alone is a strong independent risk factor for poor survival in mCRC. 

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-172517 (URN)10.1038/bjc.2012.186 (DOI)000305888400029 ()
    Tilgjengelig fra: 2012-04-11 Laget: 2012-04-11 Sist oppdatert: 2017-12-07bibliografisk kontrollert
    4. Equal cancer treatment regardless of education level and family support?: A qualitative study of oncologists’ decision-making
    Åpne denne publikasjonen i ny fane eller vindu >>Equal cancer treatment regardless of education level and family support?: A qualitative study of oncologists’ decision-making
    2012 (engelsk)Inngår i: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 2, nr 4, s. e001248-Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Objective: Treatment gradients by socioeconomic status have been observed within cancer care in several countries. The objective of this study was to explore whether patients' educational level and social network influence oncologists' clinical decision-making. Design: Semi-structured interviews on factors considered when deciding on treatment for cancer patients. Interviews were transcribed and analysed using inductive qualitative content analysis. Setting: Oncologists in Swedish university-and non-university hospitals were interviewed in their respective places of work. Participants: Twenty Swedish clinical oncologists selected through maximum-variation sampling. Primary and secondary outcome measures: Elements which influence oncologists' decision-making process were explored with focus on educational level and patients' social support systems. Results: Oncologists consciously used less combination chemotherapy for patients living alone, fearing treatment toxicity. Highly educated patients were considered as well-read, demanding and sometimes difficult to reason with. Patients with higher education, those very keen to have treatment and persuasive relatives were considered as challenges for the oncologist. Having large groups of relatives in a room made doctors feel outnumbered. A desire to please patients and relatives was posed as the main reason for giving in to patients' demands, even when this resulted in treatment with limited efficacy. Conclusions: Oncologists tailor treatment for patients living alone to avoid harmful side-effects. Many find patients' demands difficult to handle and this may result in strong socioeconomic groups being over-treated.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-172518 (URN)10.1136/bmjopen-2012-001248 (DOI)000315049300078 ()
    Tilgjengelig fra: 2012-04-11 Laget: 2012-04-11 Sist oppdatert: 2017-12-07bibliografisk kontrollert
  • 63.
    Cavalli-Björkman, Nina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Implications of patients' socioeconomic status - what oncologists should be aware of2014Inngår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 53, nr 2, s. 161-163Artikkel i tidsskrift (Annet vitenskapelig)
  • 64.
    Cavalli-Björkman, Nina
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Strang, Peter
    Equal cancer treatment regardless of education level and family support?: A qualitative study of oncologists’ decision-making2012Inngår i: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 2, nr 4, s. e001248-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: Treatment gradients by socioeconomic status have been observed within cancer care in several countries. The objective of this study was to explore whether patients' educational level and social network influence oncologists' clinical decision-making. Design: Semi-structured interviews on factors considered when deciding on treatment for cancer patients. Interviews were transcribed and analysed using inductive qualitative content analysis. Setting: Oncologists in Swedish university-and non-university hospitals were interviewed in their respective places of work. Participants: Twenty Swedish clinical oncologists selected through maximum-variation sampling. Primary and secondary outcome measures: Elements which influence oncologists' decision-making process were explored with focus on educational level and patients' social support systems. Results: Oncologists consciously used less combination chemotherapy for patients living alone, fearing treatment toxicity. Highly educated patients were considered as well-read, demanding and sometimes difficult to reason with. Patients with higher education, those very keen to have treatment and persuasive relatives were considered as challenges for the oncologist. Having large groups of relatives in a room made doctors feel outnumbered. A desire to please patients and relatives was posed as the main reason for giving in to patients' demands, even when this resulted in treatment with limited efficacy. Conclusions: Oncologists tailor treatment for patients living alone to avoid harmful side-effects. Many find patients' demands difficult to handle and this may result in strong socioeconomic groups being over-treated.

  • 65.
    Cavalli-Björkman, Nina
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Lambe, Mats
    Eaker, Sonja
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Sandin, Fredrik
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Differences according to educational level in the management and survival of colorectal cancer in Sweden2011Inngår i: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 47, nr 9, s. 1398-1406Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Socioeconomic status (SES) affects survival after a cancer diagnosis. The extent to which differences in management can explain this is not known. Record-linkage between two Swedish Regional Clinical Quality Registers of colorectal cancer and a socio-economic database generated a dataset with information on diagnostic procedures, treatment and survival in patients of different educational background. Three thousand eight hundred and ninety-nine rectal cancer patients from the years 1995 to 2006 and 5715 colon cancer patients from 1997 to 2006 were evaluated. Compared to patients with high education, those with shorter education had poorer relative and overall survival (57.9% 5-year relative survival versus 63.8% in colon cancer, 58.7% versus 69.1% in rectal cancer). There were also differences in diagnostic activity with preoperative computer tomography (40% versus 47.3%) and colonoscopy (56.3% versus 62.8%) being more frequent in highly educated groups (p = 0.001 and 0.037, respectively). Surgery resulting in colostomy was performed in 26.9% of rectal cancer patients of high education compared to 35.5% of those with low education (p = 0.005). Although rectal cancer has poorer prognosis than colon cancer, it was noted that among the highly educated, rectal cancer patients had better survival than colon cancer patients (69.1% versus 63.8% 5-year relative survival). It thus appears that improved rectal cancer management has benefited mainly patients of middle and higher educational levels. We conclude that socioeconomic differences exist in diagnostic activity and management of colorectal cancer, which may affect survival.

  • 66.
    Cavalli-Björkman, Nina
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Qvortrup, Camilla
    Sebjørnssen, Sigrunn
    Pfeiffer, Per
    Wentzel-Larsen, Tore
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Sorbye, Halfdan
    Lower treatment intensity and poorer survival in metastatic colorectal cancer patients who live alone2012Inngår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 107, nr 1, s. 189-194Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Socioeconomic status (SES) and social support influences cancer survival. If SES and social support affects cancer treatment has not been thoroughly explored. METHODS: A cohort consisting of all patients who were initially diagnosed with or who developed metastatic colorectal cancer (mCRC, n = 781) in three Scandinavian university hospitals from October 2003 to August 2006 was set up. Clinical and socioeconomic data were registered prospectively. RESULTS: Patients living alone more often had synchronous metastases at presentation and were less often treated with combination chemotherapy than those cohabitating (HR 0.19, 95% CI 0.04-0.85, P = 0.03). Surgical removal of metastases was less common in patients living alone (HR 0.29, 95% CI 0.10-0.86, P = 0.02) but more common among university-educated patients (HR 2.22, 95% CI 1.10-4.49, P = 0.02). Smoking, being married and having children did not influence treatment or survival. Median survival was 7.7 months in patients living alone and 11.7 months in patients living with someone (P < 0.001). Living alone remained a prognostic factor for survival after correction for age and comorbidity. CONCLUSION: Patients living alone received less combination chemotherapy and less secondary surgery. Living alone is a strong independent risk factor for poor survival in mCRC. 

  • 67.
    Cederblad, Lena
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Thunberg, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Engström, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Castro, Juan
    Rutqvist, Lars Erik
    Laytragoon-Lewin, Nongnit
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    The Combined Effects of Single-Nucleotide Polymorphisms, Tobacco Products, and Ethanol on Normal Resting Blood Mononuclear Cells2013Inngår i: Nicotine & tobacco research, ISSN 1462-2203, E-ISSN 1469-994X, Vol. 15, nr 5, s. 890-895Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Introduction: Tobacco and ethanol consumption are crucial factors in the development of various diseases including cancer. In this investigation, we evaluated the combined effects of a number of single nucleotide polymorphisms (SNPs), with ethanol and tobacco products on healthy individuals. Methods: Pure nicotine, cigarette smoke extract, and Swedish snuff (snus) extract were used. The effects were examined by means of in vitro cell cycle progression and cell death of peripheral blood mononuclear cells (PBMCs) obtained from healthy donors. Results: After 3 days, in vitro, resting PBMCs entered the S and G2 stage in the presence of 100 mu M nicotine. The PBMCs only proceeded to S stage, in the presence of 0.2% ethanol. The nicotine- and ethanol-induced normal cell cycle progression correlated to a number of SNPs in the IL12RB2, Rad 52, XRCC2, P53, CCND3, and ABCA1 genes. Certain SNPs in Caspases 8, IL12RB2, Rad 52, MMP2, and MDM2 genes appeared to significantly influence the effects of EtOH-, snus-, and snus + EtOH-induced cell death. Importantly, the highest degree of cell death was observed in the presence of smoke + EtOH. The amount of cell death under this treatment condition also correlated to specific SNPs, located in the MDM2, ABCA1, or GASC1 genes. Conclusions: Cigarette smoke in combination with ethanol strongly induced massive cell death. Long-term exposure to smoke and ethanol could provoke chronic inflammation, and this could be the initiation of disease including the development of cancer at various sites.

  • 68. Cerhan, James R.
    et al.
    Berndt, Sonja I.
    Vijai, Joseph
    Ghesquieres, Herve
    McKay, James
    Wang, Sophia S.
    Wang, Zhaoming
    Yeager, Meredith
    Conde, Lucia
    de Bakker, Paul I. W.
    Nieters, Alexandra
    Cox, David
    Burdett, Laurie
    Monnereau, Alain
    Flowers, Christopher R.
    De Roos, Anneclaire J.
    Brooks-Wilson, Angela R.
    Lan, Qing
    Severi, Gianluca
    Melbye, Mads
    Gu, Jian
    Jackson, Rebecca D.
    Kane, Eleanor
    Teras, Lauren R.
    Purdue, Mark P.
    Vajdic, Claire M.
    Spinelli, John J.
    Giles, Graham G.
    Albanes, Demetrius
    Kelly, Rachel S.
    Zucca, Mariagrazia
    Bertrand, Kimberly A.
    Zeleniuch-Jacquotte, Anne
    Lawrence, Charles
    Hutchinson, Amy
    Zhi, Degui
    Habermann, Thomas M.
    Link, Brian K.
    Novak, Anne J.
    Dogan, Ahmet
    Asmann, Yan W.
    Liebow, Mark
    Thompson, Carrie A.
    Ansell, Stephen M.
    Witzig, Thomas E.
    Weiner, George J.
    Veron, Amelie S.
    Zelenika, Diana
    Tilly, Herve
    Haioun, Corinne
    Molina, Thierry Jo
    Hjalgrim, Henrik
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Adami, Hans-Olov
    Bracci, Paige M.
    Riby, Jacques
    Smith, Martyn T.
    Holly, Elizabeth A.
    Cozen, Wendy
    Hartge, Patricia
    Morton, Lindsay M.
    Severson, Richard K.
    Tinker, Lesley F.
    North, Kari E.
    Becker, Nikolaus
    Benavente, Yolanda
    Boffetta, Paolo
    Brennan, Paul
    Foretova, Lenka
    Maynadie, Marc
    Staines, Anthony
    Lightfoot, Tracy
    Crouch, Simon
    Smith, Alex
    Roman, Eve
    Diver, W. Ryan
    Offit, Kenneth
    Zelenetz, Andrew
    Klein, Robert J.
    Villano, Danylo J.
    Zheng, Tongzhang
    Zhang, Yawei
    Holford, Theodore R.
    Kricker, Anne
    Turner, Jenny
    Southey, Melissa C.
    Clavel, Jacqueline
    Virtamo, Jarmo
    Weinstein, Stephanie
    Riboli, Elio
    Vineis, Paolo
    Kaaks, Rudolph
    Trichopoulos, Dimitrios
    Vermeulen, Roel C. H.
    Boeing, Heiner
    Tjonneland, Anne
    Angelucci, Emanuele
    Di Lollo, Simonetta
    Rais, Marco
    Birmann, Brenda M.
    Laden, Francine
    Giovannucci, Edward
    Kraft, Peter
    Huang, Jinyan
    Ma, Baoshan
    Ye, Yuanqing
    Chiu, Brian C. H.
    Sampson, Joshua
    Liang, Liming
    Park, Ju-Hyun
    Chung, Charles C.
    Weisenburger, Dennis D.
    Chatterjee, Nilanjan
    Fraumeni, Joseph F., Jr.
    Slager, Susan L.
    Wu, Xifeng
    de Sanjose, Silvia
    Smedby, Karin E.
    Salles, Gilles
    Skibola, Christine F.
    Rothman, Nathaniel
    Chanock, Stephen J.
    Genome-wide association study identifies multiple susceptibility loci for diffuse large B cell lymphoma2014Inngår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 46, nr 11, s. 1233-1238Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Diffuse large B cell lymphoma (DLBCL) is the most common lymphoma subtype and is clinically aggressive. To identify genetic susceptibility loci for DLBCL, we conducted a meta-analysis of 3 new genome-wide association studies (GWAS) and 1 previous scan, totaling 3,857 cases and 7,666 controls of European ancestry, with additional genotyping of 9 promising SNPs in 1,359 cases and 4,557 controls. In our multi-stage analysis, five independent SNPs in four loci achieved genome-wide significance marked by rs116446171 at 6p25.3 (EXOC2; P = 2.33 x 10(-21)), rs2523607 at 6p21.33 (HLA-B; P = 2.40 x 10(-10)), rs79480871 at 2p23.3 (NCOA1; P = 4.23 x 10(-8)) and two independent SNPs, rs13255292 and rs4733601, at 8q24.21 (PVT1; P = 9.98 x 10(-13) and 3.63 x 10(-11), respectively). These data provide substantial new evidence for genetic susceptibility to this B cell malignancy and point to pathways involved in immune recognition and immune function in the pathogenesis of DLBCL.

  • 69.
    Ciray, Ipek
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Lindman, Henrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Åström, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Bergh, J
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Ahlström, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Early response of breast cancer bone metastases to chemotherapy evaluated with MR imaging2001Inngår i: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 42, nr 2, s. 198-206Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    PURPOSE:

    To compare T1-weighted spin-echo and fat-suppressed long echo time inversion recovery turbo spin-echo (long TE IR-TSE) MR images in the evaluation of early response of breast cancer bone metastases to chemotherapy.

    MATERIAL AND METHODS:

    Eighteen breast cancer patients with known bone metastases were investigated prospectively by MR, using T1-weighted and long TE IR-TSE sequences on the sternum, spine, pelvis and proximal femora, before and after a median of 6 courses of chemotherapy. Therapeutic response evaluation with MR was based on change in tumor size assessed quantitatively by measuring all focal metastases, and change in pattern and signal intensity (SI) of the metastases, assessed visually. Combined response evaluation based on clinical findings, conventional radiography, and scintigraphy was used as reference.

    RESULTS:

    Progressive disease (2 patients) and no change (4 patients) were assessed equally well on both MR sequences. Long TE IR-TSE demonstrated partial response with higher accuracy than T1-weighted images, 58% (7/12 patients) vs. 17% (2/12 patients). In patients without progression there was an SI increase in or around the metastases in 6 patients on T1-weighted images and in 7 patients on long TE IR-TSE images.

    CONCLUSION:

    The long TE IR-TSE sequence demonstrated early partial response of breast cancer bone metastases to chemotherapy more accurately than the T1-weighted sequence.

  • 70.
    Ciray, Ipek
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Åström, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Andréasson, I
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Edekling, T
    Hansen, J
    Bergh, J
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Ahlström, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Evaluation of new sclerotic bone metastases in breast cancer patients during treatment2000Inngår i: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 41, nr 2, s. 178-182Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    PURPOSE:

    According to the World Health Organization (WHO) criteria for response of bone metastases to therapy, new lesions indicate progressive disease. We intended to prove that a new sclerotic lesion on conventional radiography may also be a sign of a positive therapeutic response in a previously undetectable lytic metastasis.

    MATERIAL AND METHODS:

    In a previous placebo-controlled clinical trial of clodronate (Ostac) therapy, 139 breast cancer patients with bone metastases underwent both conventional radiography and bone scan every 6 months for 2 years with 99mTc before and during clodronate treatment. WHO criteria were applied for therapy response evaluation.

    RESULTS:

    In 24 patients, 52 new sclerotic lesions observed during therapy were selected for re-evaluation of conventional radiographs and bone scans. In 8 of the 24 patients, 17 of 52 new sclerotic lesions (33%) had showed positive uptake on previous bone scans. These lesions were possibly misinterpreted as new when applying WHO criteria.

    CONCLUSION:

    For better assessment of new sclerotic lesions during treatment, more sensitive techniques, e.g. bone scan, are needed as a complement to conventional radiography.

  • 71.
    Ciray, Ipek
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Åström, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Sundström, Christer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi.
    Hagberg, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Ahlström, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Assessment of suspected bone metastases: CT with and without clinical information compared to CT-guided bone biopsy1997Inngår i: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 38, nr 5, s. 890-895Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    PURPOSE:

    To evaluate the role of CT with and without clinical information as compared to CT-guided bone biopsy in the assessment of suspected bone metastases.

    MATERIAL AND METHODS:

    The study comprised 51 consecutive patients with suspected bone metastases who had undergone CT-guided bone biopsies with an eccentric drill system. CT of the targets, clinical information, and histopathology were scored separately as malignant, uncertain or benign. The results of CT alone and CT in combination with clinical information were compared to the results of histopathology.

    RESULTS:

    Histopathology diagnosed 45/51 lesions (88%), 23 as malignant and 22 as benign. CT correctly depicted 17 of these 23 malignant lesions. The remaining 6 malignant lesions were CT-scored as uncertain (n = 5) or benign (n = 1). CT correctly depicted only 3 of the 22 benign lesions. The remaining 19 benign lesions were CT-scored as malignant (n = 2) or uncertain (n = 17). When uncertain CT scores were combined with clinical scores, the true-positive and true-negative results for malignancy increased from 44% to 82%.

    CONCLUSION:

    In most cases, CT in combination with clinical information gives enough information about the nature-malignant or benign-of a skeletal lesion. In uncertain cases, diagnostic accuracy can be improved by means of CT-guided bone biopsy.

  • 72. Cozen, W.
    et al.
    Timofeeva, M. N.
    Li, D.
    Diepstra, A.
    Hazelett, D.
    Delahaye-Sourdeix, M.
    Edlund, C. K.
    Franke, L.
    Rostgaard, K.
    Van Den Berg, D. J.
    Cortessis, V. K.
    Smedby, K. E.
    Glaser, S. L.
    Westra, H. -J
    Robison, L. L.
    Mack, T. M.
    Ghesquieres, H.
    Hwang, A. E.
    Nieters, A.
    de Sanjose, S.
    Lightfoot, T.
    Becker, N.
    Maynadie, M.
    Foretova, L.
    Roman, E.
    Benavente, Y.
    Rand, K. A.
    Nathwani, B. N.
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Staines, A.
    Boffetta, P.
    Link, B. K.
    Kiemeney, L.
    Ansell, S. M.
    Bhatia, S.
    Strong, L. C.
    Galan, P.
    Vatten, L.
    Habermann, T. M.
    Duell, E. J.
    Lake, A.
    Veenstra, R. N.
    Visser, L.
    Liu, Y.
    Urayama, K. Y.
    Montgomery, D.
    Gaborieau, V.
    Weiss, L. M.
    Byrnes, G.
    Lathrop, M.
    Cocco, P.
    Best, T.
    Skol, A. D.
    Adami, H. -O
    Melbye, M.
    Cerhan, J. R.
    Gallagher, A.
    Taylor, G. M.
    Slager, S. L.
    Brennan, P.
    Coetzee, G. A.
    Conti, D. V.
    Onel, K.
    Jarrett, R. F.
    Hjalgrim, H.
    van den Berg, A.
    Mckay, J. D.
    A meta-analysis of Hodgkin lymphoma reveals 19p13.3 TCF3 as a novel susceptibility locus2014Inngår i: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 5, s. 3856-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Recent genome-wide association studies (GWAS) of Hodgkin lymphoma (HL) have identified associations with genetic variation at both HLA and non-HLA loci; however, much of heritable HL susceptibility remains unexplained. Here we perform a meta-analysis of three HL GWAS totaling 1,816 cases and 7,877 controls followed by replication in an independent set of 1,281 cases and 3,218 controls to find novel risk loci. We identify a novel variant at 19p13.3 associated with HL (rs1860661; odds ratio (OR) = 0.81, 95% confidence interval (95% CI) = 0.76-0.86, P-combined 3.5 x 10(-10)), located in intron 2 of TCF3 (also known as E2A), a regulator of B-and T-cell lineage commitment known to be involved in HL pathogenesis. This meta-analysis also notes associations between previously published loci at 2p16, 5q31, 6p31, 8q24 and 10p14 and HL subtypes. We conclude that our data suggest a link between the 19p13.3 locus, including TCF3, and HL risk.

  • 73. d'Amore, Francesco
    et al.
    Leppa, Sirpa
    da Silva, Maria Comes
    Relander, Thomas
    Brown, Peter De Nully
    Weidmann, Eckhart
    Lauritzsen, Grete Fossum
    Pezzutto, Antonio
    Van Hoof, Achiel
    van Gelder, Michel
    Doorduijn, Jeanette K.
    Wu, Ka Lung
    Kluin-Nelemans, J. C.
    Lugtenburg, P. J.
    Jankovska, Milada
    Merup, Mats
    Fagerli, Unn-Merete
    Walewski, Jan
    Hagberg, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Mariz, Jose Mario
    Hansen, Per Boye
    Noesslinger, Thomas
    Janssens, Ann
    Brandefors, Lena
    Demuynck, Hilde
    Schaafsma, Martyn Ronald
    Christiansen, Ilse
    Salek, David
    Jyrkkio, Sirkku
    Prochazka, Vit
    Zijlstra, Josee
    Bohmer, L.
    Greil, Richard
    Stevens, Wendy
    Fijnheer, Rob
    Kooy, Marinus van Marwijk
    Grube, Matthias
    Hopfinger, Georg
    Van den Neste, Eric
    Jantunen, Esa
    Truemper, Lorenz
    Wulf, Gerald
    Altmann, Bettina
    Ziepert, Marita
    Loeffler, Markus
    Toldbod, Helle
    First Interim Efficacy and Safety Analysis of an International Phase III Randomized Trial in Newly Diagnosed Systemic Peripheral T-Cell Lymphoma Treated with Chemotherapy with or without Alemtuzumab and Consolidated by High Dose Therapy2012Inngår i: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 120, nr 21, s. 57-Artikkel i tidsskrift (Fagfellevurdert)
  • 74. d'Amore, Francesco
    et al.
    Relander, Thomas
    Lauritzsen, Grete F.
    Jantunen, Esa
    Hagberg, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Anderson, Harald
    Holte, Harald
    Osterborg, Anders
    Merup, Mats
    Brown, Peter
    Kuittinen, Outi
    Erlanson, Martin
    Ostenstad, Bjorn
    Fagerli, Unn-Merete
    Gadeberg, Ole V.
    Sundström, Christer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi.
    Delabie, Jan
    Ralfkiaer, Elisabeth
    Vornanen, Martine
    Toldbod, Helle E.
    Up-Front Autologous Stem-Cell Transplantation in Peripheral T-Cell Lymphoma: NLG-T-012012Inngår i: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 30, nr 25, s. 3093-3099Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose Systemic peripheral T-cell lymphomas (PTCLs) respond poorly to conventional therapy. To evaluate the efficacy of a dose-dense approach consolidated by up-front high-dose chemotherapy (HDT) and autologous stem-cell transplantation (ASCT) in PTCL, the Nordic Lymphoma Group (NLG) conducted a large prospective phase II study in untreated systemic PTCL. This is the final report, with a 5-year median follow-up, of the NLG-T-01 study. Patients and Methods Treatment-naive patients with PTCL age 18 to 67 years (median, 57 years) were included. Anaplastic lymphoma kinase (ALK) -positive anaplastic large-cell lymphoma (ALCL) was excluded. An induction regimen of six cycles of biweekly CHOEP (cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone) was administered (in patients age > 60 years, etoposide was omitted). If in complete or partial remission, patients proceeded to consolidation with HDT/ASCT. Results Of 166 enrolled patients, 160 had histopathologically confirmed PTCL. The majority presented with advanced-stage disease, B symptoms, and elevated serum lactate dehydrogenase. A total of 115 underwent HDT/ASCT, with 90 in complete remission at 3 months post-transplantation. Early failures occurred in 26%. Treatment-related mortality was 4%. At 60.5 months of median follow-up, 83 patients were alive. Consolidated 5-year overall and progression-free survival (PFS) were 51% (95% CI, 43% to 59%) and 44% (95% CI, 36% to 52%), respectively. Best results were obtained in ALK-negative ALCL. Conclusion Dose-dense induction followed by HDT/ASCT was well tolerated and led to long-term PFS in 44% of treatment-naive patients with PTCL. This represents an encouraging outcome, particularly considering the high median age and adverse risk profile of the study population. Therefore, dose-dense induction and HDT/ASCT are a rational up-front strategy in transplantation-eligible patients with PTCL. J Clin Oncol 30: 3093-3099. (C) 2012 by American Society of Clinical Oncology

  • 75. Dasu, Alexandru
    et al.
    Flejmer, Anna M.
    Dohlmar, Frida
    Josefsson, Dan
    Witt Nyström, Petra
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    The Potential Benefit of Scanned Proton Beam Versus Intensity Modulated Photon Therapy as Adjuvant Radiation Therapy in Breast Cancer2014Inngår i: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 34, nr 10, s. 5873-5874Artikkel i tidsskrift (Annet vitenskapelig)
  • 76. de Miranda, Noel F. C. C.
    et al.
    Georgiou, Konstantinos
    Chen, Longyun
    Wu, Chenglin
    Gao, Zhibo
    Zaravinos, Apostolos
    Lisboa, Susana
    Enblad, Gunilla
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Teixeira, Manuel R.
    Zeng, Yixin
    Peng, Roujun
    Pan-Hammarstrom, Qiang
    Exome sequencing reveals novel mutation targets in diffuse large B-cell lymphomas derived from Chinese patients2014Inngår i: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 124, nr 16, s. 2544-2553Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Next-generation sequencing studies on diffuse large B-cell lymphomas (DLBCLs) have revealed novel targets of genetic aberrations but also high intercohort heterogeneity. Previous studies have suggested that the prevalence of disease subgroups and cytogenetic profiles differ between Western and Asian patients. To characterize the coding genome of Chinese DLBCL, we performed whole-exome sequencing of DNA derived from 31 tumors and respective peripheral blood samples. The mutation prevalence of B2M, CD70, DTX1, LYN, TMSB4X, and UBE2A was investigated in an additional 105 tumor samples. We discovered 11 novel targets of recurrent mutations in DLBCL that included functionally relevant genes such as LYN and TMSB4X. Additional genes were found mutated at high frequency (>= 10%) in the Chinese cohort including DTX1, which was the most prevalent mutation target in the Notch pathway. We furthermore demonstrated that mutations in DTX1 impair its function as a negative regulator of Notch. Novel and previous unappreciated targets of somatic mutations in DLBCL identified in this study support the existence of additional/alternative tumorigenic pathways in these tumors. The observed differences with previous reports might be explained by the genetic heterogeneity of DLBCL, the germline genetic makeup of Chinese individuals, and/or exposure to distinct etiological agents.

  • 77. de Miranda, Noel F. C. C.
    et al.
    Peng, Roujun
    Georgiou, Konstantinos
    Wu, Chenglin
    Sörqvist, Elin Falk
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylära verktyg.
    Berglund, Mattias
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Chen, Longyun
    Gao, Zhibo
    Lagerstedt, Kristina
    Lisboa, Susana
    Roos, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    van Wezel, Tom
    Teixeira, Manuel R.
    Rosenquist, Richard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Hematologi och immunologi.
    Sundström, Christer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi.
    Enblad, Gunilla
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Nilsson, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylära verktyg. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Zeng, Yixin
    Kipling, David
    Pan-Hammarstrom, Qiang
    DNA repair genes are selectively mutated in diffuse large B cell lymphomas2013Inngår i: Journal of Experimental Medicine, ISSN 0022-1007, E-ISSN 1540-9538, Vol. 210, nr 9, s. 1729-1742Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    DNA repair mechanisms are fundamental for B cell development, which relies on the somatic diversification of the immunoglobulin genes by V(D)J recombination, somatic hypermutation, and class switch recombination. Their failure is postulated to promote genomic instability and malignant transformation in B cells. By performing targeted sequencing of 73 key DNA repair genes in 29 B cell lymphoma samples, somatic and germline mutations were identified in various DNA repair pathways, mainly in diffuse large B cell lymphomas (DLBCLs). Mutations in mismatch repair genes (EXO1, MSH2, and MSH6) were associated with microsatellite instability, increased number of somatic insertions/deletions, and altered mutation signatures in tumors. Somatic mutations in nonhomologous end-joining (NHEJ) genes (DCLRE1C/ARTEMIS, PRKDC/DNA-PKcs, XRCC5/KU80, and XRCC6/KU70) were identified in four DLBCL tumors and cytogenetic analyses revealed that translocations involving the immunoglobulin-heavy chain locus occurred exclusively in NHEJ-mutated samples. The novel mutation targets, CHEK2 and PARP1, were further screened in expanded DLBCL cohorts, and somatic as well as novel and rare germline mutations were identified in 8 and 5% of analyzed tumors, respectively. By correlating defects in a subset of DNA damage response and repair genes with genomic instability events in tumors, we propose that these genes play a role in DLBCL lymphomagenesis.

  • 78. Deb, Siddhartha
    et al.
    Johansson, Ida
    Byrne, David
    Nilsson, Cecilia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås.
    Constable, Leonie
    Fjällskog, Marie-Louise
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Dobrovic, Alexander
    Hedenfalk, Ingrid
    Fox, Stephen B.
    Nuclear HIF1A expression is strongly prognostic in sporadic but not familial male breast cancer2014Inngår i: Modern Pathology, ISSN 0893-3952, E-ISSN 1530-0285, Vol. 27, nr 9, s. 1223-1230Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Male breast cancer is poorly understood with a large proportion arising in the familial context particularly with the BRCA2 germline mutation. As phenotypic and genotypic differences between sporadic and familial male breast cancers have been noted, we investigated the importance of a hypoxic drive in these cancers as this pathway has been shown to be of importance in familial female breast cancer. Expression of two major hypoxia-induced proteins, the hypoxia-inducible factor-1 alpha (HIF1A) and the carbonic anhydrase IX (CA9), examined within a large cohort including 61 familial (3 BRCA1, 28 BRCA2, 30 BRCAX) and 225 sporadic male breast cancers showed that 31% of all male breast cancers expressed either HIF1A (25%) and/or CA9 (8%) in the combined cohort. Expression of HIF1A correlated with an increased incidence of a second-major malignancy (P=0.04), histological tumor type (P=0.005) and basal phenotype (P=0.02). Expression of CA9 correlated with age (P=0.004) in sporadic cases and an increased tumor size (P=0.003). Expression of HIF1A was prognostic for disease-specific survival in sporadic male breast cancers (HR: 3.8, 95% CI: 1.5-9.8, P=0.006) but not within familial male breast cancer, whereas CA9 was only prognostic in familial male breast cancers (HR: 358.0, 95% CI: 9.3-13781.7, P=0.002) and not in sporadic male breast cancer. This study found that hypoxic drive is less prevalent in male breast cancer compared with female breast cancer, possibly due to a different breast microenvironment. The prognostic impact of HIF1A is greatest in sporadic male breast cancers with an alternate dominant mechanism for the oncogenic drivers suggested in high risk familial male breast cancers.

  • 79.
    Delforoush, Maryam
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Berglund, Mattias
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Enblad, Gunilla
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Molecular Studies of Mechanisms of Drug Resistance in Malignant Cells With Focus on Lymphomas2012Inngår i: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 48, nr S5, s. S229-S229Artikkel i tidsskrift (Fagfellevurdert)
  • 80. Dewdney, Alice
    et al.
    Cunningham, David
    Tabernero, Josep
    Capdevila, Jaume
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Cervantes, Andres
    Tait, Diana
    Brown, Gina
    Wotherspoon, Andrew
    de Castro, David Gonzalez
    Chua, Yu Jo
    Wong, Rachel
    Barbachano, Yolanda
    Oates, Jacqueline
    Chau, Ian
    Multicenter Randomized Phase II Clinical Trial Comparing Neoadjuvant Oxaliplatin, Capecitabine, and Preoperative Radiotherapy With or Without Cetuximab Followed by Total Mesorectal Excision in Patients With High-Risk Rectal Cancer (EXPERT-C)2012Inngår i: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 30, nr 14, s. 1620-1627Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose To evaluate the addition of cetuximab to neoadjuvant chemotherapy before chemoradiotherapy in high-risk rectal cancer.

    Patients and Methods Patients with operable magnetic resonance imaging-defined high-risk rectal cancer received four cycles of capecitabine/oxaliplatin (CAPOX) followed by capecitabine chemoradiotherapy, surgery, and adjuvant CAPOX (four cycles) or the same regimen plus weekly cetuximab (CAPOX + C). The primary end point was complete response (CR; pathologic CR or, in patients not undergoing surgery, radiologic CR) in patients with KRAS/BRAF wild-type tumors. Secondary end points were radiologic response (RR), progression-free survival (PFS), overall survival (OS), and safety in the wild-type and overall populations and a molecular biomarker analysis.

    Results One hundred sixty-five eligible patients were randomly assigned. Ninety (60%) of 149 assessable tumors were KRAS or BRAF wild type (CAPOX, n = 44; CAPOX + C, n = 46), and in these patients, the addition of cetuximab did not improve the primary end point of CR (9% v 11%, respectively; P = 1.0; odds ratio, 1.22) or PFS (hazard ratio [ HR], 0.65; P = .363). Cetuximab significantly improved RR (CAPOX v CAPOX + C: after chemotherapy, 51% v 71%, respectively; P = .038; after chemoradiation, 75% v 93%, respectively; P = .028) and OS (HR, 0.27; P = .034). Skin toxicity and diarrhea were more frequent in the CAPOX + C arm.

    Conclusion Cetuximab led to a significant increase in RR and OS in patients with KRAS/BRAF wild-type rectal cancer, but the primary end point of improved CR was not met.

  • 81. Dias, M M
    et al.
    Pignon, J-P
    Karapetis, C S
    Boige, V
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Kweekel, D M
    Lara, P N
    Laurent-Puig, P
    Martinez-Balibrea, E
    Páez, D
    Punt, C J A
    Redman, M W
    Toffoli, G
    Wadelius, Mia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    McKinnon, R A
    Sorich, M J
    The effect of the UGT1A1*28 allele on survival after irinotecan-based chemotherapy: a collaborative meta-analysis2014Inngår i: The Pharmacogenomics Journal, ISSN 1470-269X, E-ISSN 1473-1150, Vol. 14, nr 5, s. 424-431Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    To date, studies of irinotecan pharmacogenetics have mostly focused on the effect of the UGT1A1*28 allele on irinotecan-related toxicity. However, the clinical utility of routine UGT1A1*28 genotyping to pre-emptively adjust irinotecan dosage is dependent upon whether UGT1A1*28 also affects patient survival following irinotecan therapy. Previous observational studies evaluating the influence of UGT1A1*28 on survival have shown contradictory results. A systematic review and meta-analysis of both published and unpublished data were performed to summarize the available evidence of the relationship between the UGT1A1*28 allele and patient survival related to irinotecan therapy. Overall and progression-free survival meta-analysis data were available for 1524 patients and 1494 patients, respectively. The difference in the survival between patients of different UGT1A1*28 genotypes (homozygous, heterozygous or wild-type) who had received irinotecan was not found to be statistically significant. There was also no evidence of irinotecan dose, regimen or line of therapy having an impact on this association.

  • 82. Du, Likun
    et al.
    Peng, Roujun
    Björkman, Andrea
    Filipe de Miranda, Noel
    Rosner, Cornelia
    Kotnis, Ashwin
    Berglund, Mattias
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Liu, Chonghai
    Rosenquist, Richard
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Hematologi och immunologi.
    Enblad, Gunilla
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Sundström, Christer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi.
    Hojjat-Farsangi, Mohammad
    Rabbani, Hodjattallah
    Teixeira, Manuel R
    Revy, Patrick
    Durandy, Anne
    Zeng, Yixin
    Gennery, Andrew R
    de Villartay, Jean-Pierre
    Pan-Hammarström, Qiang
    Cernunnos influences human immunoglobulin class switch recombination and may be associated with B cell lymphomagenesis2012Inngår i: Journal of Experimental Medicine, ISSN 0022-1007, E-ISSN 1540-9538, Vol. 209, nr 2, s. 291-305Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Cernunnos is involved in the nonhomologous end-joining (NHEJ) process during DNA double-strand break (DSB) repair. Here, we studied immunoglobulin (Ig) class switch recombination (CSR), a physiological process which relies on proper repair of the DSBs, in B cells from Cernunnos-deficient patients. The pattern of in vivo generated CSR junctions is altered in these cells, with unusually long microhomologies and a lack of direct end-joining. The CSR junctions from Cernunnos-deficient patients largely resemble those from patients lacking DNA ligase IV, Artemis, or ATM, suggesting that these factors are involved in the same end-joining pathway during CSR. By screening 269 mature B cell lymphoma biopsies, we also identified a somatic missense Cernunnos mutation in a diffuse large B cell lymphoma sample. This mutation has a dominant-negative effect on joining of a subset of DNA ends in an in vitro NHEJ assay. Translocations involving both Ig heavy chain loci and clonal-like, dynamic IgA switching activities were observed in this tumor. Collectively, our results suggest a link between defects in the Cernunnos-dependent NHEJ pathway and aberrant CSR or switch translocations during the development of B cell malignancies.

  • 83. Dueland, Svein
    et al.
    Guren, Tormod K.
    Hagness, Morten
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Line, Pal-Dag
    Pfeiffer, Per
    Foss, Aksel
    Tveit, Kjell M.
    Chemotherapy or Liver Transplantation for Nonresectable Liver Metastases From Colorectal Cancer?2015Inngår i: Annals of Surgery, ISSN 0003-4932, E-ISSN 1528-1140, Vol. 261, nr 5, s. 956-960Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: The primary objective was to compare overall survival (OS) in patients with colorectal cancer (CRC) with nonresectable liver-only metastases treated by liver transplantation or chemotherapy. Background: CRC is the third most common cancer worldwide. About 50% of patients will develop metastatic disease primarily to the liver and the lung. The majority of patients with liver metastases receive palliative chemotherapy, with a median OS of trial patients of about 2 years, and less than 10% are alive at 5 years. Methods: Patients with nonresectable liver-only CRC metastases underwent liver transplantation in the SECA study (n = 21). Disease-free survival (DFS) and OS of patients included in the SECA study were compared with progression-free survival (PFS) and OS in a similar cohort of CRC patients with liver-only disease included in a first-line chemotherapy study, the NORDIC VII study (n = 47). PFS/DFS and OS were estimated by the Kaplan-Meier method. Results: DFS/PFS in both groups were 8 to 10 months. However, a dramatic difference in OS was observed. The 5-year OS rate was 56% in patients undergoing liver transplantation compared with 9% in patients starting first-line chemotherapy. The reason for the large difference in OS despite similar DFS/PFS is likely different metastatic patterns at relapse/progression. Relapse in the liver transplantation group was often detected as small, slowly growing lung metastases, whereas progression of nonresectable liver metastases was observed in the chemotherapy group. Conclusions: Compared with chemotherapy, liver transplantation resulted in a marked increased OS in CRC patients with nonresectable liver-only metastases.

  • 84. Dueland, Svein
    et al.
    Kyrre, Tormod
    Hagness, Guren Morten
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Line, Pal-Dag
    Pfeiffer, Per
    Foss, Aksel
    Tveit, Kjell Magne
    Outcome after liver transplantation compared with chemotherapy in colorectal cancer patients with nonresectable liver-only disease.2014Inngår i: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 32, nr 3Artikkel i tidsskrift (Annet vitenskapelig)
  • 85.
    Edlund, Karolina
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi.
    Lindskog, Cecilia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi.
    Saito, Akira
    Berglund, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Pontén, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi.
    Göransson-Kultima, Hanna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Isaksson, Anders
    Jirström, Karin
    Planck-Sturegård, Maria
    Johansson, Leif
    Lambe, Mats
    Holmberg, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Nyberg, Fredrik
    Ekman, Simon
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Bergqvist, Michael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Landelius, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Thoraxkirurgi.
    Lamberg, Kristina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Lungmedicin och allergologi.
    Botling, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi.
    Östman, Arne
    Micke, Patrick
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi.
    CD99 is a novel prognostic stromal marker in non-small cell lung cancer2012Inngår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 131, nr 10, s. 2264-2273Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The complex interaction between cancer cells and the microenvironment plays an essential role in all stages of tumourigenesis. Despite the significance of this interplay, alterations in protein composition underlying tumour-stroma interactions are largely unknown. The aim of this study was to identify stromal proteins with clinical relevance in non-small cell lung cancer (NSCLC). A list encompassing 203 stromal candidate genes was compiled based on gene expression array data and available literature. The protein expression of these genes in human NSCLC was screened using the Human Protein Atlas. Twelve proteins were selected that showed a differential stromal staining pattern (BGN, CD99, DCN, EMILIN1, FBN1, PDGFRB, PDLIM5, POSTN, SPARC, TAGLN, TNC, VCAN). The corresponding antibodies were applied on tissue microarrays, including 190 NSCLC samples, and stromal staining was correlated with clinical parameters. Higher stromal expression of CD99 was associated with better prognosis in the univariate (p=0.037) and multivariate (p=0.039) analysis. The association was independent from the proportion of tumour stroma, the fraction of inflammatory cells, and clinical and pathological parameters like stage, performance status and tumour histology. The prognostic impact of stromal CD99 protein expression was confirmed in an independent cohort of 240 NSCLC patients (p=0.008). Furthermore, double-staining confocal fluorescence microscopy showed that CD99 was expressed in stromal lymphocytes as well as in cancer associated fibroblasts. Based on a comprehensive screening strategy the membrane protein CD99 was identified as a novel stromal factor with clinical relevance. The results support the concept that stromal properties have an important impact on tumour progression.

  • 86. Edlund, Per
    et al.
    Ahlgren, Johan
    Bjerre, Karsten
    Andersson, Michael
    Bergh, Jonas
    Mouridsen, Henning
    Holmberg, Stig B.
    Bengtsson, Nils-Olof
    Jakobsen, Erik
    Moller, Susanne
    Lindman, Henrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Blomqvist, Carl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Dose-tailoring of FEC adjuvant chemotherapy based on leukopenia is feasible and well tolerated. Toxicity and dose intensity in the Scandinavian Breast Group phase 3 adjuvant Trial SBG 2000-12011Inngår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 50, nr 3, s. 329-337Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The SBG 2000-1 trial is a randomised study that investigates if dose-tailored adjuvant FEC therapy based on the individual's leukocyte nadir value can improve outcome. The study has included 1535 women with medium and high-risk breast cancer. Patients and methods. After a first standard dosed FEC course (5-fluorouracil 600 mg/m(2), epirubicin 60 mg/mg(2) and cyclophosphamide 600 mg/m(2)), patients who did not reach leukopenia grade III or IV were randomised to standard doses (group standard) or doses tailored to achieve grade III leukopenia (group tailored) at courses 2 7. Patients who achieved leukopenia grade III or more after the first course were not randomised but continued on standard doses (group registered). Results. Both planned and actually delivered number of courses (seven) were the same in all three arms. The relative dose intensity was increased by a factor of 1.31 (E 1.22, C 1.43) for patients in the tailored arm compared to the expected on standard dose. Ninety percent of the patients in the tailored arm achieved leukopenia grade III-IV compared with 29% among patients randomised to standard dosed therapy. Dose tailoring was associated with acceptable acute non-haematological toxicity with more total alopecia, nausea, vomiting and fatigue. Conclusion. Dose tailoring according to leukopenia was feasible. It led to an increased dose intensity and was associated with acceptable excess of acute non-haematological toxicity.

  • 87.
    Eklund, Karin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Ahnesjö, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Avdelningen för sjukhusfysik. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Modeling silicon diode dose response factors for small photon fields2010Inngår i: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 55, nr 24, s. 7411-7423Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The dosimetry of small fields is important for the use of high resolution photon radiotherapy. Silicon diodes yield a high signal from a small detecting volume which makes them suitable for use in small fields and high dose gradients. Unshielded diodes used in large fields are known to give a varying dose response depending on the proportion of low energy scattered photons in the field. Response variations in small fields can be caused by both spectral variations, and disturbances of the local level of lateral electron equilibrium. We present a model that includes the effects from lack of charged particle equilibrium. The local spectra are calculated by use of fluence pencil kernels and divided into a low and a high energy component. The low energy part is treated with large cavity theory and the high energy part with the Spencer-Attix small cavity theory. Monte Carlo-derived correction factors are used to account for both the local level of electron equilibrium in the field, and deviations from this level in the silicon disk cavity. Results for field sizes ranging from 0.5 × 0.5 to 20 × 20 cm2 are compared to data from full Monte Carlo simulations and measurements. The achieved dose response accuracy is for the smallest fields 1-2%, and for larger fields 0.5%. Spectral variations were of little importance for the small field response, implying that volume averaging, and to some extent interface transient effects, are of importance for use of unshielded diodes in non-equilibrium conditions. The results indicate that diodes should preferably be designed to have the thin layer of active volume padded in between inactive layers of the silicon base material.

  • 88.
    Eklund, Karin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Avdelningen för sjukhusfysik. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Ahnesjö, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Avdelningen för sjukhusfysik. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Modeling silicon diode energy response factors for use in therapeutic photon beams2009Inngår i: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 54, nr 20, s. 6135-6150Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Silicon diodes have good spatial resolution, which makes them advantageous over ionization chambers for dosimetry in fields with high dose gradients. However, silicon diodes overrespond to low-energy photons, that are more abundant in scatter which increase with large fields and larger depths. We present a cavity-theory-based model for a general response function for silicon detectors at arbitrary positions within photon fields. The model uses photon and electron spectra calculated from fluence pencil kernels. The incident photons are treated according to their energy through a bipartition of the primary beam photon spectrum into low- and high-energy components. Primary electrons from the high-energy component are treated according to Spencer–Attix cavity theory. Low-energy primary photons together with all scattered photons are treated according to large cavity theory supplemented with an energy-dependent factor K(E) to compensate for energy variations in the electron equilibrium. The depth variation of the response for an unshielded silicon detector has been calculated for 5 × 5 cm2, 10 × 10 cm2 and 20 × 20 cm2 fields in 6 and 15 MV beams and compared with measurements showing that our model calculates response factors with deviations less than 0.6%. An alternative method is also proposed, where we show that one can use a correlation with the scatter factor to determine the detector response of silicon diodes with an error of less than 3% in 6 MV and 15 MV photon beams.

  • 89.
    Ekman, Simon
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Frödin, Jan-Erik
    Harmenberg, Johan
    Bergman, Antonina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Hedlund, Åsa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Dahg, Pia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Alvfors, Carina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
    Ståhl, Birgitta
    Bergström, Stefan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Bergqvist, Michael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Clinical Phase I study with an Insulin-like Growth Factor-1 Receptor Inhibitor: Experiences in patients with squamous non-small cell lung carcinoma2011Inngår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 50, nr 3, s. 441-447Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background. Inhibition of the Insulin-like Growth Factor-1 receptor (IGF-1R) has resulted in extensive anti-tumor effects. Picropdophyllin (PPP, AXL1717) is a small-molecule inhibitor of the IGF-1R without inhibition of closely related receptors including the insulin receptor and has shown extensive effects against a wide range of tumors in animals. PPP is currently tested as an orally administrated single agent treatment in an open-label combined Phase I/II clinical study in advanced cancer patients with solid tumors which progress in spite of several lines of treatment. Patients and methods. The first part (Phase IA) consisted of single day BID dosing every three weeks with consecutive dose escalations. The second part (Phase IB) consists of seven days or longer BID dosing every three weeks, dosing range being 520-700 mg BID. Non-progressing patients could continue treatment within a compassionate use setting. Results and discussion. The present report describes our experience with the four patients with progressive squamous non-small cell lung cancer (NSCLC) that have received treatment with PPP. Despite more than seven months of PPP treatment as third or fourth line treatment, the reported patients did not develop any additional metastases. Furthermore, CT scans as well as (18)FDG-Positron Emission Tomography (PET) scans of the patients demonstrated large central necrotic areas, which may suggest tumor response. At the same time, the study drug is so far well tolerated. The phenomenon of necrosis in the tumors suggestive of tumor response has not been reported before in anti-IGF-1R treatment and will be subject to further studies in the present clinical trial.

  • 90. Ellin, Fredrik
    et al.
    Jerkeman, Mats
    Hagberg, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Relander, Thomas
    Treatment outcome in T-cell lymphoblastic lymphoma in adults: a population-based study from the Swedish Lymphoma Registry2014Inngår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 53, nr 7, s. 927-934Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background. T-cell lymphoblastic lymphoma (T-LBL) is a rare neoplasm of precursor lymphoblast origin, for which there is no standard treatment for adults. Results of current treatment strategies in selected populations do exist but are largely unreported for unselected series. Here, we aimed to investigate treatment outcome in a population-based cohort. Material and methods. Patients were identified through the Swedish Lymphoma Registry and data was retrospectively collected for all adult (>= 18 years) Swedish T-LBL patients diagnosed during 2000-2009. Results. A total of 39 patients with median age 40 years (range 18-78) were identified with females being significantly older than males (median age 66 vs. 37, p = 0.027). The five-year overall survival for all patients was 42%. Female gender was associated with shorter survival also when adjusted for treatment strategy and age [hazard ratio (HR) 4.29; p = 0.002]. Thirty patients received intensive chemotherapy, otherwise used for treatment of acute lymphoblastic leukemia (ALL), which resulted in an overall response rate of 97% and a five-year progression-free survival (PFS) of 49%. In this group only CNS involvement at diagnosis predicted shorter PFS (HR 13.3; p = 0.03). Among patients treated with hyper-CVAD the addition of mediastinal irradiation resulted in prolonged time to progression compared to patients receiving only chemotherapy (p = 0.047). The major reason for treatment failure was relapse and in this series 18-fluoro-deoxyglucose positron emission tomography (PET) did not predict this risk. Conclusion. This population-based study indicates that all fit T-LBL patients should be considered for intensive treatment. Our results also suggest a beneficial effect of mediastinal irradiation in combination with hyper-CVAD treatment. Relapsing patients have a dismal outcome irrespective of salvage treatment.

  • 91. Elliot, A. H.
    et al.
    Martling, A.
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Nordenvall, C.
    Johansson, H.
    Nilsson, P. J.
    Preoperative treatment selection in rectal cancer: A population-based cohort study2014Inngår i: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 40, nr 12, s. 1782-1788Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Preoperative radiotherapy and chemoradiotherapy for rectal cancer reduce local recurrence rates but is also associated with side effects. Thus, it is important to identify patients in whom the benefits exceed the risks. This study assessed the pretherapeutic parameters influencing the selection to preoperative treatment. Methods: Data on all patients in the Stockholm-Gotland area, Sweden, who underwent elective trans-abdominal surgery for rectal cancer in 2000-2010, was retrieved from the Regional Cancer Registry and the Swedish National Patient Register. Clinical variables were analysed in relation to selected preoperative therapy. Odds Ratios were derived from univariable and multivariable logistic regression models. Results: In total 2619 patients were included. Of these 1789 (68.3%) received preoperative radiotherapy or chemoradiotherapy. Over time, use of preoperative therapy increased (p < 0.001). In a multivariable model, age (>= 80 years) and comorbidity (Charlson Comorbidity Index score >= 2) were strongly correlated to omittance of preoperative treatment (OR: 0.05; 95% CI: 0.04-0.07 and 0.29; 95% CI: 0.21-0.39) but there was no difference between genders. Pre-treatment tumour stage was a strong predictor for selection to preoperative (chemo-) radiotherapy. However, 8.2% of patients with intermediate or advanced tumours were selected to no preoperative treatment while 55.0% of patients with early tumours were selected to preoperative therapy. Conclusions: The use of preoperative (chemo-) radiotherapy increased over time. Suboptimal adherence to guidelines appears to exist leading to a risk of overtreatment and to a small extent also undertreatment. More robust selection criteria, also including age and comorbidity should be developed.

  • 92.
    Elsir, Tamador
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Edqvist, Per-Henrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Carlson, Joseph
    Ribom, Dan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Bergqvist, Michael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Ekman, Simon
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Popova, Svetlana N
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi.
    Alafuzoff, Irina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi.
    Pontén, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylär och morfologisk patologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Nistér, Monica
    Smits, Anja
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    A study of embryonic stem cell-related proteins in human astrocytomas: Identification of Nanog as a predictor of survival2014Inngår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 134, nr 5, s. 1123-1131Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Recent studies suggest that the regulatory networks controlling the functions of stem cells during development may be abnormally active in human cancers. An embryonic stem cell (ESC) gene signature was found to correlate with a more undifferentiated phenotype of several human cancer types including gliomas, and associated with poor prognosis in breast cancer. In the present study, we used tissue microarrays of 80 low-grade (WHO grade II) and 98 high-grade human gliomas (WHO grade III and IV) to investigate the presence of the ESC-related proteins Nanog, Klf4, Oct4, Sox2 and c-Myc by immunohistochemistry. While similar patterns of co-expressed proteins between low- and high-grade gliomas were present, we found up-regulated protein levels of Nanog, Klf4, Oct4 and Sox2 in high-grade gliomas. Survival analysis by Kaplan-Meier analysis revealed a significant shorter survival in the subgroups of low-grade astrocytomas (n=42) with high levels of Nanog protein (p=0.0067) and of Klf4 protein (p=0.0368), in high-grade astrocytomas (n=85) with high levels of Nanog (p=0.0042), Klf4 (p=0.0447), and c-Myc (p=0.0078) and in glioblastomas only (n=71) with high levels of Nanog (p=0.0422) and of c-Myc (p= 0.0256). In the multivariate model, Nanog was identified as an independent prognostic factor in the subgroups of low-grade astrocytomas (p=0.0039), high-grade astrocytomas (p=0.0124) and glioblastomas only (p=0.0544), together with established clinical variables in these tumors. These findings provide further evidence for the joint regulatory pathways of ESC-related proteins in gliomas and identify Nanog as one of the key players in determining clinical outcome of human astrocytomas.

  • 93. Enciso-Mora, Victor
    et al.
    Broderick, Peter
    Ma, Yussanne
    Jarrett, Ruth F.
    Hjalgrim, Henrik
    Hemminki, Kari
    van den Berg, Anke
    Olver, Bianca
    Lloyd, Amy
    Dobbins, Sara E.
    Lightfoot, Tracy
    van Leeuwen, Flora E.
    Foersti, Asta
    Diepstra, Arjan
    Broeks, Annegien
    Vijayakrishnan, Jayaram
    Shield, Lesley
    Lake, Annette
    Montgomery, Dorothy
    Roman, Eve
    Engert, Andreas
    von Strandmann, Elke Pogge
    Reiners, Katrin S.
    Nolte, Ilja M.
    Smedby, Karin E.
    Adami, Hans-Olov
    Russell, Nicola S.
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Hamilton-Dutoit, Stephen
    de Bruin, Marieke
    Ryder, Lars P.
    Molin, Daniel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Sorensen, Karina Meden
    Chang, Ellen T.
    Taylor, Malcolm
    Cooke, Rosie
    Hofstra, Robert
    Westers, Helga
    van Wezel, Tom
    van Eijk, Ronald
    Ashworth, Alan
    Rostgaard, Klaus
    Melbye, Mads
    Swerdlow, Anthony J.
    Houlston, Richard S.
    A genome-wide association study of Hodgkin's lymphoma identifies new susceptibility loci at 2p16.1 (REL), 8q24.21 and 10p14 (GATA3)2010Inngår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 42, nr 12, s. 1126-1130Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    To identify susceptibility loci for classical Hodgkin's lymphoma (cHL), we conducted a genome-wide association study of 589 individuals with cHL (cases) and 5,199 controls with validation in four independent samples totaling 2,057 cases and 3,416 controls. We identified three new susceptibility loci at 2p16.1 (rs1432295, REL, odds ratio (OR) = 1.22, combined P = 1.91 × 10−8), 8q24.21 (rs2019960, PVT1, OR = 1.33, combined P = 1.26 × 10−13) and 10p14 (rs501764, GATA3, OR = 1.25, combined P = 7.05 × 10−8). Furthermore, we confirmed the role of the major histocompatibility complex in disease etiology by revealing a strong human leukocyte antigen (HLA) association (rs6903608, OR = 1.70, combined P = 2.84 × 10−50). These data provide new insight into the pathogenesis of cHL.

  • 94.
    Enger, Shirin A.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Fisher, Darrell R.
    Flynn, Ryan T.
    Gadolinium-153 as a brachytherapy isotope2013Inngår i: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 58, nr 4, s. 957-964Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The purpose of this work was to present the fundamental dosimetric characteristics of a hypothetical Gd-153 brachytherapy source using the AAPM TG-43U1 dose-calculation formalism. Gadolinium-153 is an intermediate-energy isotope that emits 40-100 keV photons with a half-life of 242 days. The rationale for considering Gd-153 as a brachytherapy source is for its potential of patient specific shielding and to enable reduced personnel shielding requirements relative to Ir-192, and as an isotope for interstitial rotating shield brachytherapy (I-RSBT). A hypothetical Gd-153 brachytherapy source with an active core of 0.84 mm diameter, 10 mm length and specific activity of 5.55 TBq of Gd-153 per gram of Gd was simulated with Geant4. The encapsulation material was stainless steel with a thickness of 0.08 mm. The radial dose function, anisotropy function and photon spectrum in water were calculated for the Gd-153 source. The simulated Gd-153 source had an activity of 242 GBq and a dose rate in water 1 cm off axis of 13.12 Gy h(-1), indicating that it would be suitable as a low-dose-rate or pulsed-dose-rate brachytherapy source. The beta particles emitted have low enough energies to be absorbed in the source encapsulation. Gadolinium-153 has an increasing radial dose function due to multiple scatter of low-energy photons. Scattered photon dose takes over with distance from the source and contributes to the majority of the absorbed dose. The anisotropy function of the Gd-153 source decreases at low polar angles, as a result of the long active core. The source is less anisotropic at polar angles away from the longitudinal axes. The anisotropy function increases with increasing distance. The Gd-153 source considered would be suitable as an intermediate-energy low-dose-rate or pulsed-dose-rate brachytherapy source. The source could provide a means for I-RSBT delivery and enable brachytherapy treatments with patient specific shielding and reduced personnel shielding requirements relative to Ir-192.

  • 95.
    Eriksson, Fredrik
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Tötterman, Thomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Maltais, Anna-Karin
    Pisa, Pavel
    Yachnin, Jeffrey
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    DNA vaccine coding for the rhesus prostate specific antigen delivered by intradermal electroporation in patients with relapsed prostate cancer2013Inngår i: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 31, nr 37, s. 3843-3848Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We tested safety, clinical efficacy and immunogenicity of a DNA vaccine coding for rhesus prostate specific antigen (PSA) delivered by intradermal injection and skin electroporation. Fifteen patients with biochemical relapse of prostate cancer without macroscopic disease participated in this phase I study. Patients were started on a 1 month course of androgen deprivation therapy (ADT) prior to treatment. Vaccine doses ranged from 50 to 1600 mu g. Study subjects received five vaccinations at four week intervals. All patients have had at least one year of follow-up. No systemic toxicity was observed. Discomfort from electroporation did not require analgesia or topical anesthetic. No clinically significant changes in PSA kinetics were observed as all patients required antiandrogen therapy shortly after completion of the 5 months of vaccination due to rising PSA. Immunogenicity, as measured by T-cell reactivity to the modified PSA peptide and to a mix of overlapping PSA peptides representing the full length protein, was observed in some patients. All but one patient had pre-study PSA specific T-cell reactivity. ADT alone resulted in increases in T-cell reactivity in most patients. Intradermal vaccination with skin electroporation is easily performed with only minor discomfort for the patient. Patients with biochemical relapse of prostate cancer are a good model for testing immune therapies.

  • 96. Eriksson, H.
    et al.
    Lyth, J.
    Mansson-Brahme, E.
    Frohm-Nilsson, M.
    Ingvar, C.
    Lindholm, C.
    Naredi, P.
    Stierner, U.
    Wagenius, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Carstensen, J.
    Hansson, J.
    Low level of education is associated with later stage at diagnosis and reduced survival in cutaneous malignant melanoma: A nationwide population-based study in Sweden2013Inngår i: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 49, nr 12, s. 2705-2716Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: A worse outcome has been reported for cutaneous malignant melanoma (CMM) patients with low socioeconomic status. We have investigated the association between level of education, clinical stage at diagnosis (stage at diagnosis) and CMM-specific survival in Sweden. Methods: We identified 27,235 patients from the Swedish Melanoma Register diagnosed with a primary invasive CMM between 1990 and 2007 and linked data to nationwide, population-based, health and census registers with a follow-up to 2010. Results: The odds ratio (OR) of higher disease stage at diagnosis was significantly increased in lower education groups (OR stage II versus I = 1.6; 95% confidence interval (CI) = 1.5-1.7. OR stage III-IV versus I = 2.3; 95% CI = 1.8-2.9). The risk of dying of CMM, was significantly increased in patients with low (hazard ratio (HR) low versus high = 2.02; 95% CI = 1.80-2.26; p < 0.0001) and intermediate (HR intermediate versus high = 1.35; 95% CI = 1.20-1.51; p < 0.0001) level of education. After adjustment for age, gender, stage at diagnosis and other known prognostic factors, the HRs remained significant for low versus high (HR = 1.13; 95% CI = 1.01-1.27; p = 0.04) but not for intermediate versus high (HR = 1.11; 95% CI = 0.99-1.24; p = 0.08) education. The HR associated with low level of education was significantly higher among female patients, patients <55 years, patients with truncal tumours and during the first 5 years after diagnosis. Conclusion: Lower level of education is associated with reduced CMM-specific survival, which may at least partially be attributed to a more advanced stage at diagnosis. These results emphasise the need for improved early detection strategies. 

  • 97.
    Eriksson, Jonas
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET.
    Åberg, Ola
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET.
    Selvaraju, Ram K
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET.
    Antoni, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Johansson, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap.
    Eriksson, Olof
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET.
    Strategy to develop a MAO-A-resistant 5-hydroxy-L-[beta-C-11]tryptophan isotopologue based on deuterium kinetic isotope effects2014Inngår i: EJNMMI Research, ISSN 2191-219X, E-ISSN 2191-219X, Vol. 4, nr 1, artikkel-id 62Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background

    The serotonin precursor 5-hydroxy-L-[β-11C]tryptophan ([11C]HTP) is in clinical use for localization of neuroendocrine tumors and has been suggested as a proxy marker for pancreatic islet cells. However, degradation by monoamine oxidase-A (MAO-A) reduces retention and the contrast to non-endocrine tissue.

    Methods

    A synthesis method was developed for 5-hydroxy-L-[β-11C2H]tryptophan ([11C]DHTP), an isotopologue of [11C]HTP, labeled with 11C and 2H at the β-position adjacent to the carbon involved in MAO-A decarboxylation. MAO-A-mediated degradation of [11C]DHTP was evaluated and compared to non-deuterated [11C]HTP.

    Results

    [11C]DHTP was synthesized with a radiochemical purity of >98%, radioactivity of 620 ± 190 MBq, and deuterium (2H or 2H2) incorporation at the β-position of 22% ±5%. Retention and resistance to MAO-A-mediated degradation of [11C]DHTP were increased in cells but not in non-human primate pancreas.

    Conclusions

    Partial deuteration of the β-position yields improved resistance to MAO-A-mediated degradation in vitro but not in vivo.

  • 98.
    Eriksson, Olof
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET.
    Espes, Daniel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Selvaraju, Ram K
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET.
    Jansson, Emma
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Antoni, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Sörensen, Jens
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för nuklearmedicin och PET.
    Lubberink, Mark
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för nuklearmedicin och PET.
    Biglarnia, Alireza
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Transplantationskirurgi.
    Eriksson, Jan W
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Sundin, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Ahlström, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Eriksson, Barbro
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Johansson, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Carlsson, Per-Ola
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Transplantation och regenerativ medicin.
    Korsgren, Olle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    The Positron Emission Tomography ligand [11C]5-Hydroxy-Tryptophan can be used as a surrogate marker for the human endocrine pancreas2014Inngår i: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 63, nr 10, s. 3428-3437Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In humans a well-developed serotonin system is localized to the pancreatic islets while being absent in exocrine pancreas. Assessment of pancreatic serotonin biosynthesis could therefore be used to estimate the human endocrine pancreas. Proof of concept was tested in a prospective clinical trial by comparisons of type 1 diabetic (T1D) patients, with extensive reduction of beta cells, with healthy volunteers (HV).C-peptide negative (i.e. insulin-deficient) T1D subjects (n=10) and HV (n=9) underwent dynamic Positron Emission Tomography with the radiolabeled serotonin precursor [(11)C]5-Hydroxy-Tryptophan ([(11)C]5-HTP).A significant accumulation of [(11)C]5-HTP was obtained in the pancreas of the HV, with large inter-individual variation. A substantial and highly significant reduction (66%) in the pancreatic uptake of [(11)C]5-HTP in T1D subjects was observed, and this was most evident in the corpus and caudal regions of the pancreas where beta-cells normally are the major constituent of the islets.[(11)C]5-HTP retention in the pancreas was reduced in T1D compared to non-diabetic subjects. Accumulation of [(11)C]5-HTP in the pancreas of both HV and subjects with T1D were in agreement with previously reported morphological observations on the beta cell volume implying that [(11)C]5-HTP retention is a useful non-invasive surrogate marker for the human endocrine pancreas.

  • 99.
    Eriksson, Olof
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Sadeghi, Arian
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Carlsson, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Eich, Torsten
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Lundgren, Torbjörn
    Nilsson, Bo
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Tötterman, Thomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Korsgren, Olle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Sundin, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Distribution of adoptively transferred porcine T-lymphoblasts tracked by (18)F-2-fluoro-2-deoxy-D-glucose and position emission tomography2011Inngår i: Nuclear Medicine and Biology, ISSN 0969-8051, E-ISSN 1872-9614, Vol. 38, nr 6, s. 827-833Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Introduction: Autologous or allogeneic transfer of tumor-infiltrating T-Iymphocytes is a promising treatment for metastatic cancers, but a major concern is the difficulty in evaluating cell trafficking and distribution in adoptive cell therapy. This study presents a method of tracking transfusion of T-Iymphoblasts in a porcine model by (18)F-2-fluoro-2-deoxy-D-glucose ([(18)F]FDG) and positron emission tomography. Methods: T-Iymphoblasts were labeled with the positron-emitting tracer [(18)F]FDG through incubation. The T-Iymphoblasts were administered into the bloodstream, and the distribution was followed by positron emission tomography for 120 min. The cells were administered either intravenously into the internal jugular vein (n=5) or intraarterially into the ascending aorta (n=1). Two of the pigs given intravenous administration were pretreated with low-molecular-weight dextran sulphate. Results: The cellular kinetics and distribution were readily quantifiable for up to 120 min. High (78.6% of the administered cells) heterogeneous pulmonary uptake was found after completed intravenous transfusion. The pulmonary uptake was decreased either by preineubating and coadministrating the T-Iymphoblasts with low-molecular-weight dextran sulphate or by administrating them intraarterially. Conclusions: The present work shows the feasibility of quantitatively monitoring and evaluating cell trafficking and distribution following administration of [(18)F]FDG-labeled T-Iymphoblasts. The protocol can potentially be transferred to the clinical setting with few modifications.

  • 100.
    Eriksson, Olof
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET.
    Selvaraju, Ram K
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET.
    Johansson, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Eriksson, Jan W
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Sundin, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Antoni, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Sörensen, Jens
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för nuklearmedicin och PET.
    Eriksson, Barbro
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Korsgren, Olle
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Quantitative Imaging of Serotonergic Biosynthesis and Degradation in the Endocrine Pancreas2014Inngår i: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 55, nr 3, s. 460-465Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Serotonergic biosynthesis in the endocrine pancreas, of which the islets of Langerhans is the major constituent, has been implicated in insulin release and β cell proliferation. In this study, we investigated the feasibility of quantitative noninvasive imaging of the serotonergic metabolism in the pancreas using the PET tracer (11)C-5-hydroxy-l-tryptophan ((11)C-5-HTP).

    METHODS: Uptake of (11)C-5-HTP, and its specificity for key enzymes in the serotonergic metabolic pathway, was assessed in vitro (INS-1 and PANC1 cells and human islet and exocrine preparations) and in vivo (nonhuman primates and healthy and diabetic rats).

    RESULTS: In vitro tracer uptake in endocrine cells (INS-1 and human islets), but not PANC1 and exocrine cells, was mediated specifically by intracellular conversion into serotonin. Pancreatic uptake of (11)C-5-HTP in nonhuman primates was markedly decreased by inhibition of the enzyme dopa decarboxylase, which converts (11)C-5-HTP to (11)C-serotonin and increased after inhibition of monoamine oxidase-A, the main enzyme responsible for serotonin degradation. Uptake in the rat pancreas was similarly modulated by inhibition of monoamine oxidase-A and was reduced in animals with induced diabetes.

    CONCLUSION: The PET tracer (11)C-5-HTP can be used for quantitative imaging of the serotonergic system in the endocrine pancreas.

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