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  • 1.
    Ahlström, Håkan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Ekström, Simon
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Sjöholm, Therese
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Strand, Robin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Johansson, E.
    Antaros Med, Molndal, Sweden..
    Hagmar, P.
    Antaros Med, Molndal, Sweden..
    Malmberg, Filip
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Registration-based automated lesion detection and therapy evaluation of tumors in whole body PET-MR images2017In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 28, no S5, article id 78PArticle in journal (Other academic)
  • 2. Andersson, Jenny
    et al.
    Larsson, L.
    Klaar, S.
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Nilsson, J.
    Inganäs, M.
    Carlsson, G.
    Ohd, J.
    Rudenstam, C-M.
    Gustavsson, B.
    Bergh, J.
    Worse survival for TP53 (p53)-mutated breast cancer patients receiving adjuvant CMF2005In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 16, no 5, p. 743-8Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: TP53 has been described as a prognostic factor in many malignancies, including breast cancer. Whether it also might be a predictive factor with reference to chemo- and endocrine therapy is more controversial. PATIENTS AND METHODS: We investigated relapse-free (RFS), breast cancer-corrected (BCCS) and overall survival (OS) related to TP53 status in node-positive breast cancer patients that had received polychemotherapy [cyclophosphamide, methotrexate, 5-fluorouracil (CMF)] and/or endocrine therapy (tamoxifen). Sequence analyses of the whole TP53 coding region was performed in 376 patients operated on for primary breast cancer with axillary lymph node metastases between 1984 and 1989 (median follow-up time 84 months). RESULTS: TP53 mutations were found in 105 patients (28%). We found 90 (82%) of the 110 mutations in the more frequently analysed exons 5-8, while the other 20 (18%) were located in exons 3-4 and 9-10, respectively. Univariate analyses showed TP53 to be a significant prognostic factor with regard to RFS, BCCS and OS in patients who received adjuvant CMF. CONCLUSIONS: TP53 mutations might induce resistance to certain modalities of breast cancer therapy. Sequence-determined TP53 mutation was of negative prognostic value in the total patient population and in the CMF treated patients.

  • 3.
    Berglund, U. Warpman
    et al.
    Karolinska Inst, Dept Med Biochem & Biophys, Div Translat Med & Chem Biol, Sci Life Lab, Stockholm, Sweden..
    Sanjiv, K.
    Karolinska Inst, Dept Med Biochem & Biophys, Div Translat Med & Chem Biol, Sci Life Lab, Stockholm, Sweden..
    Gad, H.
    Karolinska Inst, Dept Med Biochem & Biophys, Div Translat Med & Chem Biol, Sci Life Lab, Stockholm, Sweden..
    Kalderen, C.
    Karolinska Inst, Dept Med Biochem & Biophys, Div Translat Med & Chem Biol, Sci Life Lab, Stockholm, Sweden..
    Koolmeister, T.
    Karolinska Inst, Dept Med Biochem & Biophys, Div Translat Med & Chem Biol, Sci Life Lab, Stockholm, Sweden..
    Pham, T.
    Karolinska Inst, Dept Med Biochem & Biophys, Div Translat Med & Chem Biol, Sci Life Lab, Stockholm, Sweden..
    Gokturk, C.
    Karolinska Inst, Dept Med Biochem & Biophys, Div Translat Med & Chem Biol, Sci Life Lab, Stockholm, Sweden..
    Jafari, R.
    Karolinska Inst, Dept Oncol Pathol, Clin Prote Mass Spectrometry, Stockholm, Sweden..
    Maddalo, G.
    Karolinska Inst, Dept Oncol Pathol, Clin Prote Mass Spectrometry, Stockholm, Sweden..
    Seashore-Ludlow, B.
    Karolinska Inst, Div Translat Med & Chem Biol, Dept Med Biochem & Biophys, Chem Biol Consortium Sweden,Sci Life Lab, Stockholm, Sweden..
    Chernobrovkin, A.
    Karolinska Inst, Dept Med Biochem & Biophys, Div Physiol Chem 1, Stockholm, Sweden..
    Manoilov, A.
    Karolinska Inst, Dept Med Biochem & Biophys, Div Physiol Chem 1, Stockholm, Sweden..
    Pateras, I. S.
    Univ Athens, Sch Med, Dept Histol & Embryol, Mol Carcinogenesis Grp, Athens, Greece..
    Rasti, A.
    Karolinska Inst, Dept Med Biochem & Biophys, Div Translat Med & Chem Biol, Sci Life Lab, Stockholm, Sweden..
    Jemth, A. -S
    Almlof, I.
    Karolinska Inst, Dept Med Biochem & Biophys, Div Translat Med & Chem Biol, Sci Life Lab, Stockholm, Sweden..
    Loseva, O.
    Karolinska Inst, Dept Med Biochem & Biophys, Div Translat Med & Chem Biol, Sci Life Lab, Stockholm, Sweden..
    Visnes, T.
    Karolinska Inst, Dept Med Biochem & Biophys, Div Translat Med & Chem Biol, Sci Life Lab, Stockholm, Sweden..
    Einarsdottir, B. O.
    Univ Gothenburg, Inst Clin Sci, Sahlgrenska Translat Melanoma Grp SATMEG, Sahlgrenska Canc Ctr,Dept Surg, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Gothenburg, Sweden..
    Gaugaz, Fabienne Z.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy. Karolinska Inst, Dept Med Biochem & Biophys, Div Translat Med & Chem Biol, Sci Life Lab, Stockholm, Sweden..
    Saleh, Aljona
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Platzack, B.
    Swedish Toxicol Sci Res Ctr, Sodertalje, Sweden..
    Wallner, O. A.
    Karolinska Inst, Dept Med Biochem & Biophys, Div Translat Med & Chem Biol, Sci Life Lab, Stockholm, Sweden..
    Vallin, K. S. A.
    Karolinska Inst, Dept Med Biochem & Biophys, Div Translat Med & Chem Biol, Sci Life Lab, Stockholm, Sweden..
    Henriksson, M.
    Karolinska Inst, Dept Med Biochem & Biophys, Div Translat Med & Chem Biol, Sci Life Lab, Stockholm, Sweden..
    Wakchaure, P.
    Karolinska Inst, Dept Med Biochem & Biophys, Div Translat Med & Chem Biol, Sci Life Lab, Stockholm, Sweden..
    Borhade, S.
    Karolinska Inst, Dept Med Biochem & Biophys, Div Translat Med & Chem Biol, Sci Life Lab, Stockholm, Sweden..
    Herr, P.
    Karolinska Inst, Dept Med Biochem & Biophys, Div Translat Med & Chem Biol, Sci Life Lab, Stockholm, Sweden..
    Kallberg, Y.
    Karolinska Inst, Dept Med Solna, Sci Life Lab, NBIS, Stockholm, Sweden..
    Baranczewski, Pawel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy. Uppsala University, Science for Life Laboratory, SciLifeLab. Karolinska Inst, Dept Med Biochem & Biophys, Div Translat Med & Chem Biol, Sci Life Lab, Stockholm, Sweden..
    Homan, E. J.
    Karolinska Inst, Dept Med Biochem & Biophys, Div Translat Med & Chem Biol, Sci Life Lab, Stockholm, Sweden..
    Wiita, E.
    Karolinska Inst, Dept Med Biochem & Biophys, Div Translat Med & Chem Biol, Sci Life Lab, Stockholm, Sweden..
    Nagpal, V.
    Karolinska Inst, Dept Med Biochem & Biophys, Div Translat Med & Chem Biol, Sci Life Lab, Stockholm, Sweden.;SP Proc Dev, Sodertalje, Sweden..
    Meijer, T.
    SP Proc Dev, Sodertalje, Sweden..
    Schipper, N.
    SP Proc Dev, Sodertalje, Sweden..
    Rudd, S. G.
    Karolinska Inst, Dept Med Biochem & Biophys, Div Translat Med & Chem Biol, Sci Life Lab, Stockholm, Sweden..
    Brautigam, L.
    Karolinska Inst, Dept Med Biochem & Biophys, Div Translat Med & Chem Biol, Sci Life Lab, Stockholm, Sweden..
    Lindqvist, Annika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Filppula, Anne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Lee, T-C
    Artursson, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Nilsson, J. A.
    Univ Gothenburg, Inst Clin Sci, Sahlgrenska Translat Melanoma Grp SATMEG, Sahlgrenska Canc Ctr,Dept Surg, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Gothenburg, Sweden..
    Gorgoulis, V. G.
    Acad Athens, Biomed Res Fdn, Athens, Greece.;Univ Manchester, Manchester Acad Hlth Sci Ctr, Fac Inst Canc Sci, Manchester, Lancs, England..
    Lehtio, J.
    Karolinska Inst, Dept Oncol Pathol, Clin Prote Mass Spectrometry, Stockholm, Sweden..
    Zubarev, R. A.
    Karolinska Inst, Dept Med Biochem & Biophys, Div Physiol Chem 1, Stockholm, Sweden..
    Scobie, M.
    Karolinska Inst, Dept Med Biochem & Biophys, Div Translat Med & Chem Biol, Sci Life Lab, Stockholm, Sweden..
    Helleday, T.
    Karolinska Inst, Dept Med Biochem & Biophys, Div Translat Med & Chem Biol, Sci Life Lab, Stockholm, Sweden..
    Validation and development of MTH1 inhibitors for treatment of cancer2016In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 27, no 12, p. 2275-2283Article in journal (Refereed)
    Abstract [en]

    Background: Previously, we showed cancer cells rely on the MTH1 protein to prevent incorporation of otherwise deadly oxidised nucleotides into DNA and we developed MTH1 inhibitors which selectively kill cancer cells. Recently, several new and potent inhibitors of MTH1 were demonstrated to be non-toxic to cancer cells, challenging the utility of MTH1 inhibition as a target for cancer treatment. Material and methods: Human cancer cell lines were exposed in vitro to MTH1 inhibitors or depleted of MTH1 by siRNA or shRNA. 8-oxodG was measured by immunostaining and modified comet assay. Thermal Proteome profiling, proteomics, cellular thermal shift assays, kinase and CEREP panel were used for target engagement, mode of action and selectivity investigations of MTH1 inhibitors. Effect of MTH1 inhibition on tumour growth was explored in BRAF V600E-mutated malignant melanoma patient derived xenograft and human colon cancer SW480 and HCT116 xenograft models. Results: Here, we demonstrate that recently described MTH1 inhibitors, which fail to kill cancer cells, also fail to introduce the toxic oxidized nucleotides into DNA. We also describe a new MTH1 inhibitor TH1579, (Karonudib), an analogue of TH588, which is a potent, selective MTH1 inhibitor with good oral availability and demonstrates excellent pharmacokinetic and anti-cancer properties in vivo. Conclusion: We demonstrate that in order to kill cancer cells MTH1 inhibitors must also introduce oxidized nucleotides into DNA. Furthermore, we describe TH1579 as a best-in-class MTH1 inhibitor, which we expect to be useful in order to further validate the MTH1 inhibitor concept.

  • 4.
    Berglund, Åke
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Cedermark, B
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Is it deleterious to delay the start of adjuvant chemotherapy in colon cancer stage III?2008In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 19, no 2, p. 400-402Article in journal (Refereed)
  • 5. Bergqvist, Jenny
    et al.
    Ohd, J. F.
    Smeds, J.
    Klaar, Sigrid
    Isola, J.
    Nordgren, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Pathology.
    Elmberger, G. P.
    Hellborg, H.
    Bjohle, J.
    Borg, A-L.
    Skoog, L.
    Bergh, J.
    Quantitative real-time PCR analysis and microarray-based RNA expression of HER2 in relation to outcome2007In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 18, no 5, p. 845-850Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Our aim was to use quantitative real-time PCR (Q-PCR) and RNA expression profiles (RNA-EPs) to investigate HER2 status in relation to outcome. PATIENTS AND METHODS: Cut-off levels for Q-PCR and RNA-EP were established in relation to immunohistochemistry (IHC) validated by FISH in a test set of frozen tissue samples from 40 primary breast cancers. The HER2 status was subsequently studied in another validation set of 306 tumors, where Q-PCR and RNA-EP results were compared with previously carried out IHC that we had validated by chromogenic in situ hybridization (CISH). RESULTS: Q-PCR and RNA-EP offered similar sensitivity (90% versus 77%), specificity (93% versus 95%), and negative (99% versus 98%) and positive (63% versus 61%) predictive values for HER2 determinations. Analyses of relapse-free survival (RFS) and overall survival on the basis of 5 and 10 years of follow-up indicated equivalent hazard ratios for all three techniques. In contrast to IHC/CISH, both Q-PCR and RNA-EP analyses of HER2 also gave statistically significant results regarding RFS and breast cancer-corrected survival after 10 years of follow-up. CONCLUSION: The use of RNA-EP and Q-PCR to analyze HER2 in frozen and formalin-fixed breast cancer samples may be an alternate approach to IHC in combination with FISH/CISH.

  • 6. Björkholm, Magnus
    et al.
    Hagberg, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Holte, H.
    Kvaloy, S.
    Teerenhovi, L.
    Anderson, H.
    Cavallin-Ståhl, E.
    Myhre, J.
    Pertovaara, H.
    Öst, Å.
    Nilsson, B.
    Ösby, E.
    Central nervous system occurrence in elderly patients with aggressive lymphoma and a long-term follow-up2007In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 18, no 6, p. 1085-1089Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Secondary central nervous system (CNS) involvement by aggressive lymphoma is a well-known and dreadful clinical complication. The incidence and risk factors for CNS manifestation were studied in a large cohort of elderly (>60 years) patients with aggressive lymphoma. PATIENTS AND METHODS: In all, 444 previously untreated patients were randomized to receive 3-weekly combination chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone or cyclophosphamide, mitoxantrone, vincristine and prednisone (CNOP) (doxorubicin substituted by mitoxantrone) chemotherapy with or without filgrastim. Prophylactic intrathecal methotrexate was given to patients with lymphoma involvement of bone marrow, testis and CNS near sites. RESULTS: In all 29 of 444 (6.5%) developed CNS disease after a median observation time of 115 months. CNS was the only site of progression/relapse in 13 patients while part of a systemic disease manifestation in 16 patients. In univariate risk factor analysis, CNS occurrence was associated with extranodal involvement of testis (P = 0.002), advanced clinical stage (P = 0.005) and increased age-adjusted International Prognostic Index score (aaIPI; P = 0.035). In multivariate analysis, initial involvement of testis remained significant and clinical stage was of borderline significance. The median survival time was 2 months after presentation of CNS disease. CONCLUSION: A significant proportion of elderly patients with advanced aggressive lymphoma will develop CNS disease. CNS occurrence is related to testis involvement, advanced clinical stage and high aaIPI and the prognosis is dismal.

  • 7. Breugom, A. J.
    et al.
    van Gijn, W.
    Muller, E. W.
    Berglund, Åke
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science.
    van den Broek, C. B. M.
    Fokstuen, T.
    Gelderblom, H.
    Kapiteijn, E.
    Leer, J. W. H.
    Marijnen, C. A. M.
    Martijn, H.
    Kranenbarg, E. Meershoek-Klein
    Nagtegaal, I. D.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Punt, C. J. A.
    Putter, H.
    Roodvoets, A. G. H.
    Rutten, H. J. T.
    Steup, W. H.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    van de Velde, C. J. H.
    Adjuvant chemotherapy for rectal cancer patients treated with preoperative (chemo)radiotherapy and total mesorectal excision: a Dutch Colorectal Cancer Group (DCCG) randomized phase III trial2015In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 26, no 4, p. 696-701Article in journal (Refereed)
    Abstract [en]

    Background: The discussion on the role of adjuvant chemotherapy for rectal cancer patients treated according to current guidelines is still ongoing. A multicentre, randomized phase III trial, PROCTOR-SCRIPT, was conducted to compare adjuvant chemotherapy with observation for rectal cancer patients treated with preoperative (chemo) radiotherapy and total mesorectal excision (TME). Patients and methods: The PROCTOR-SCRIPT trial recruited patients from 52 hospitals. Patients with histologically proven stage II or III rectal adenocarcinoma were randomly assigned (1: 1) to observation or adjuvant chemotherapy after preoperative (chemo) radiotherapy and TME. Radiotherapy consisted of 5 x 5 Gy. Chemoradiotherapy consisted of 25 x 1.8-2 Gy combined with 5-FU-based chemotherapy. Adjuvant chemotherapy consisted of 5-FU/LV (PROCTOR) or eight courses capecitabine (SCRIPT). Randomization was based on permuted blocks of six, stratified according to centre, residual tumour, time between last irradiation and surgery, and preoperative treatment. The primary end point was overall survival. Results: Of 470 enrolled patients, 437 were eligible. The trial closed prematurely because of slow patient accrual. Patients were randomly assigned to observation (n = 221) or adjuvant chemotherapy (n = 216). After a median follow-up of 5.0 years, 5-year overall survival was 79.2% in the observation group and 80.4% in the chemotherapy group [hazard ratio (HR) 0.93, 95% confidence interval (CI) 0.62-1.39; P = 0.73]. The HR for disease-free survival was 0.80 (95% CI 0.60-1.07; P = 0.13). Five-year cumulative incidence for locoregional recurrences was 7.8% in both groups. Five-year cumulative incidence for distant recurrences was 38.5% and 34.7%, respectively (P = 0.39). Conclusion: The PROCTOR-SCRIPT trial could not demonstrate a significant benefit of adjuvant chemotherapy with fluoropyrimidine monotherapy after preoperative (chemo) radiotherapy and TME on overall survival, disease-free survival, and recurrence rate. However, this trial did not complete planned accrual.

  • 8. Byström, P.
    et al.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Reply to FDG-PET: for early prediction of response to the first-line chemotherapy in metastatic colorectal cancer?2009In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 20, no 6, p. 1150-1150Article in journal (Refereed)
  • 9. Byström, Per
    et al.
    Berglund, A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Garske, Ulrike Garske
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Jacobsson, H.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Nygren, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Frödin, J-E.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Early prediction of response to first-line chemotherapy by sequential [18F]-2-fluoro-2-deoxy-D-glucose positron emission tomography in patients with advanced colorectal cancer2009In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 20, no 6, p. 1057-1061Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: To evaluate [(18)F]-2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET), for early evaluation of response to palliative chemotherapy and for prediction of long-term outcome, in patients with metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: In a randomized trial, patients with mCRC received irinotecan-based combination chemotherapy. FDG-PET was carried out before treatment and after two cycles in 51 patients at two centers. Visual changes in tumor FDG uptake and changes measured semi-automatically, as standard uptake values (SUVs), were compared with radiological response after four and eight cycles. RESULTS: The mean baseline SUV for all tumor lesions per patient was higher in nonresponders than in responders (mean 7.4 versus 5.6, P = 0.02). There was a strong correlation between metabolic response (changes in SUV) and objective response (r = 0.57, P = 0.00001), with a sensitivity of 77% and a specificity of 76%. There was no significant correlation between metabolic response and time to progression (P = 0.5) or overall survival (P = 0.1). CONCLUSIONS: Although metabolic response assessed by FDG-PET reflects radiological tumor volume changes, the sensitivity and specificity are too low to support the routine use of PET in mCRC. Furthermore, PET failed to reflect long-term outcome and can, thus, not be used as surrogate end point for hard endpoint benefit.

  • 10. Caplin, M. E.
    et al.
    Baudin, E.
    Ferolla, P.
    Filosso, P.
    Garcia-Yuste, M.
    Lim, E.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Pelosi, G.
    Perren, A.
    Rossi, R. E.
    Travis, W. D.
    Pulmonary neuroendocrine (carcinoid) tumors: European Neuroendocrine Tumor Society expert consensus and recommendations for best practice for typical and atypical pulmonary carcinoids2015In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 26, no 8, p. 1604-1620Article in journal (Refereed)
    Abstract [en]

    Background: Pulmonary carcinoids (PCs) are rare tumors. As there is a paucity of randomized studies, this expert consensus document represents an initiative by the European Neuroendocrine Tumor Society to provide guidance on their management. Patients and methods: Bibliographical searches were carried out in PubMed for the terms 'pulmonary neuroendocrine tumors', 'bronchial neuroendocrine tumors', 'bronchial carcinoid tumors', 'pulmonary carcinoid', 'pulmonary typical/atypical carcinoid', and 'pulmonary carcinoid and diagnosis/treatment/epidemiology/prognosis'. A systematic review of the relevant literature was carried out, followed by expert review. Results: PCs are well-differentiated neuroendocrine tumors and include low-and intermediate-grade malignant tumors, i.e. typical (TC) and atypical carcinoid (AC), respectively. Contrast CT scan is the diagnostic gold standard for PCs, but pathology examination is mandatory for their correct classification. Somatostatin receptor imaging may visualize nearly 80% of the primary tumors and is most sensitive for metastatic disease. Plasma chromogranin A can be increased in PCs. Surgery is the treatment of choice for PCs with the aim of removing the tumor and preserving as much lung tissue as possible. Resection of metastases should be considered whenever possible with curative intent. Somatostatin analogs are the first-line treatment of carcinoid syndrome and may be considered as first-line systemic antiproliferative treatment in unresectable PCs, particularly of low-grade TC and AC. Locoregional or radiotargeted therapies should be considered for metastatic disease. Systemic chemotherapy is used for progressive PCs, although cytotoxic regimens have demonstrated limited effects with etoposide and platinum combination the most commonly used, however, temozolomide has shown most clinical benefit. Conclusions: PCs are complex tumors which require a multidisciplinary approach and long-term follow-up.

  • 11. Carducci, M.
    et al.
    Armstrong, A.
    Haggman, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Stadler, W. M.
    Gingrich, J. R.
    Assikis, V.
    Forsberg, G.
    Olsson, A.
    Nordle, O.
    Pili, R.
    Tasquinimod mechanism of action biomarkers: correlation with pfs and survival in men with metastatic castrate resistant prostate cancer treated in a randomized phase 2 trial2012In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 23, no S9, p. 303-303Article in journal (Other academic)
  • 12.
    Cashin, Peter H
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Nygren, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Mahteme, Haile
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Intraoperative hyperthermic versus postoperative normothermic intraperitoneal chemotherapy for colonic peritoneal carcinomatosis: a case-control study2012In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 23, no 3, p. 647-652Article in journal (Refereed)
    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.

  • 13. De Graan, A. M.
    et al.
    Elens, L.
    Sparreboom, A.
    Friberg, Lena E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    van der Holt, B.
    De Raaf, P. J.
    Wiemer, E. A. C.
    Verweij, J.
    van Schaik, R. H.
    Mathijssen, R. H. J.
    Influence of drug exposure and genetic variation on paclitaxel-induced neurotoxicity2012In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 23, no S9, p. 534-534Article in journal (Other academic)
  • 14.
    de Kruijf, E M
    et al.
    Departments of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
    Dekker, T J A
    Departments of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
    Hawinkels, L J A C
    Departments of Molecular Cell Biology and Centre for Biomedical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
    Putter, H
    Departments of Medical Statistics, Leiden University Medical Center, Leiden, The Netherlands.
    Smit, V T H B M
    Departments of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
    Kroep, J R
    Departments of Medical Oncology, Leiden University Medical Center, Leiden, The Netherlands.
    Kuppen, P J K
    Departments of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
    van de Velde, C J H
    Departments of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
    ten Dijke, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwig Institute for Cancer Research.
    Tollenaar, R A E M
    Departments of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
    Mesker, W E
    Departments of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
    The prognostic role of TGF-β signaling pathway in breast cancer patients2013In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 24, no 2, p. 384-390Article in journal (Refereed)
    Abstract [en]

    Background

    The transforming growth factor-β (TGF-β) pathway has dual effects on tumor growth. Seemingly, discordant results have been published on the relation between TGF-β signaling markers and prognosis in breast cancer. Improved prognostic information for breast cancer patients might be obtained by assessing interactions among TGF-β signaling biomarkers.

    Patients and methods

    The expression of nuclear Smad4, nuclear phosphorylated-Smad2 (p-Smad2), and the membranous expression of TGF-β receptors I and II (TβRI and TβRII) was determined on a tissue microarray of 574 breast carcinomas. Tumors were stratified according to the Smad4 expression in combination with p-Smad2 expression or Smad4 in combination with the expression of both TGF-β receptors.

    Results

    Tumors with high expression of TβRII, TβRI and TβRII, and p-Smad2 (P = 0.018, 0.005, and 0.022, respectively), and low expression of Smad4 (P = 0.005) had an unfavorable prognosis concerning progression-free survival. Low Smad4 expression combined with high p-Smad2 expression or low expression of Smad4 combined with high expression of both TGF-β receptors displayed an increased hazard ratio of 3.04 [95% confidence interval (CI) 1.390-6.658] and 2.20 (95% CI 1.464-3.307), respectively, for disease relapse.

    Conclusions

    Combining TGF-β biomarkers provides prognostic information for patients with stage I-III breast cancer. This can identify patients at increased risk for disease recurrence that might therefore be candidates for additional treatment.

  • 15. Fazio, N
    et al.
    de Braud, F
    Delle Fave, G
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Interferon-{alpha} and somatostatin analog in patients with gastroenteropancreatic neuroendocrine carcinoma: single agent or combination?2007In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 18, no 1, p. 13-19Article, review/survey (Refereed)
    Abstract [en]

    In most cases gastro-enteropancreatic neuroendocrine tumors grow slowly. Interferon-α and somatostatin analogs have shown symptomatic, biochemical, and, in a minority of cases, antiproliferative activity. Generally, they are proposed as single-agent therapy. However, based on in vitro and in vivo evidence, the combined use of these drugs was proposed in several non-randomized trials, indicating that there is an additive effect of the combination. Nevertheless, the three randomized trials published so far did not show a statistically significant survival benefit for the combination compared to the same agents alone, even though an advantage for the combination came out in all three studies. On the other hand, data from non-randomized trials would justify the sequential use of the two drugs or the combination after progression on single agent therapy. Therefore, at present the up-front combined use of interferon-α and somatostatin analog is not justified, whereas it could be indicated after progression to single-agent therapy. Further larger, international, prospective, randomized, multicentric clinical trials studying homogeneous populations would be necessary to give a final answer, but the rarity and heterogeneity of this malignancy does not assure that it will be possible.

  • 16.
    Ferolla, P.
    et al.
    Umbria Reg Canc Network, Multidisciplinary NET Grp, Dept Med Oncol, Perugia, Italy.;Univ Perugia, Perugia, Italy..
    Brizzi, M. P.
    Univ Turin, Dept Oncol, Turin, Italy..
    Meyer, T.
    Royal Free Hosp, Oncol, London, England.;UCL, London, England..
    Mansoor, W.
    Christie NHS Fdn Trust, Dept Med Oncol, Manchester, Lancs, England..
    Mazieres, J.
    Hop Larrey, CHU Toulouse, Med Oncol, Toulouse, France..
    Cao, C. D.
    CHRU Lille, Med Oncol, Lille, France..
    Lena, H.
    Ctr Hosp Univ, Pneumol, Rennes, France..
    Berruti, A.
    Univ Brescia, Med Oncol, Brescia, Italy..
    Damiano, V.
    Azienda Osped Univ Policlin Federico II AOU Feder, Dept Dip Oncol, Endocr Mol Clin, Naples, Italy..
    Buikhuisen, W.
    Netherlands Canc Inst, Dept Thorac Oncol, Amsterdam, Netherlands..
    Stankovic, M.
    Novartis Pharma Serv Inc, Med Affairs, Novi Beograd, Serbia..
    Singh, N.
    Cognizant Technol Solut, PLS Clin Project Mgt, Bombay, Maharashtra, India..
    Chiodini, E.
    Parexel, Clin, Origgio, Italy..
    Gislimberti, G.
    OORE GMO, Gislimberti, Origgio, Italy..
    Öberg, Kjell E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Baudin, E.
    Inst Gustave Roussy, Endocrinol, Villejuif, France..
    Efficacy and safety of pasireotide LAR or everolimus alone, or in combination in patients with advanced carcinoids (NET) of the lung/thymus: Results from the randomized, phase 2 LUNA study2016In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 27, no 6, article id 4160Article in journal (Refereed)
  • 17. Foukakis, T.
    et al.
    Åström, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Lindström, L.
    Hatschek, T.
    Bergh, J.
    When to order a biopsy to characterise a metastatic relapse in breast cancer2012In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 23, p. 349-353Article in journal (Refereed)
    Abstract [en]

    Today, the diagnosis of metastatic breast cancer is usually based on radiological findings, and therapeutic decisions are made by considering the pathological characteristics and predictive markers of the primary tumour. Accumulating evidence suggests that tumour characteristics, including estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2), are unstable through tumour progression. Several retrospective studies and, recently, two prospective studies have investigated the discrepancies in receptor status between primary tumours and the corresponding metastases in a total of 1773 patients (for ER) and 2845 patients (for HER2). Changes in ER and HER2 status in these studies range from 14.5% to 40% and from 0% to 37.5%, respectively. In the two prospective studies, a different diagnosis, usually non-malignant, was obtained in 3% and 9% of the cases, and the biopsy led to a treatment modification in about one out of seven patients. Here, we review and discuss the currently available data and provide our recommendations on when a metastatic biopsy should be obtained.

  • 18. Frederiksen, C.
    et al.
    Qvortrup, C.
    Christensen, I. J.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Berglund, Åke
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Jensen, B. V.
    Nielsen, S. E.
    Keldsen, N.
    Nielsen, H. J.
    Brunner, N.
    Pfeiffer, P.
    Plasma TIMP-1 levels and treatment outcome in patients treated with XELOX for metastatic colorectal cancer2011In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 22, no 2, p. 369-375Article in journal (Refereed)
    Abstract [en]

    Background: The aim was to evaluate the association between plasma tissue inhibitor of metalloproteinase-1 (TIMP-1) and serum carcinoembryonic antigen (CEA) levels and outcome in patients with metastatic colorectal cancer (mCRC) receiving XELOX (combination chemotherapy with capecitabine and oxaliplatin) as first-line treatment. Patients and methods: One hundred and twenty patients were included. Blood samples were collected before treatment and 3 weeks later before the next treatment cycle. Plasma TIMP-1 and serum CEA levels were correlated to treatment outcome. Results: No significant associations between baseline TIMP-1 or CEA levels and best response to treatment or progression-free survival (PFS) could be demonstrated. In contrast, high baseline plasma TIMP-1 levels were associated with poor overall survival (OS), P = 0.008, hazard ratio (HR) = 1.80 [95% confidence interval (CI): 1.17-2.78]. Furthermore, increase in TIMP-1 levels from baseline to immediately before the second cycle of chemotherapy had a significant negative effect on survival (P = 0.03, HR = 1.30, 95% CI: 1.02-1.65) while a decrease in TIMP-1 was significantly associated with a higher objective response rate (P = 0.03). Conclusions: Both high baseline and subsequent increase in TIMP-1 levels were associated with shorter OS in patients with mCRC receiving XELOX as first-line treatment, whereas baseline TIMP-1 levels were not associated with response or PFS following XELOX treatment.

  • 19.
    Frenzel, K.
    et al.
    BioNTech Grp Mainz, Mainz, Germany..
    Heesen, L.
    BioNTech Grp Mainz, Mainz, Germany..
    Bolte, S.
    BioNTech Grp Mainz, Mainz, Germany..
    Bukur, V.
    BioNTech Grp Mainz, Mainz, Germany..
    Diken, M.
    TRON gGmbH, TRON, Mainz, Germany..
    Derhovanessian, E.
    BioNTech Grp Mainz, Mainz, Germany..
    Kreiter, S.
    BioNTech Grp Mainz, Mainz, Germany..
    Kuhn, A.
    BioNTech Grp Mainz, Mainz, Germany..
    Kuehlcke, K.
    EUFETS GmbH, Idar Oberstein, Germany..
    Löwer, M.
    TRON gGmbH, TRON, Mainz, Germany..
    De Greve, J.
    UZ Brussels, Dept Med & Mol Oncol, Brussels, Belgium..
    Lindman, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Pascolo, S.
    Univ Zurich, URPP Translat Canc Res, Zurich, Switzerland..
    Schmidt, M.
    Univ Med Mainz, Klin & Poliklin Geburtshilfe & Frauengesundheit, Mainz, Germany..
    Schneeweiss, A.
    NCT Heidelberg, Sekt Gynakol Onkol, Heidelberg, Germany..
    Sjöblom, Tobias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Thielemans, K.
    Univ Hosp Brussels, Dept Immunol Physiol, Brussels, Belgium..
    Zitvogel, L.
    Gustave Roussy Inst Cancerol, Tumour Immunol & Immunotherapy, Villejuif, France..
    Tuereci, Ö.
    CI3 Cluster Individualized Immunointervent, Mainz, Germany..
    Sahin, U.
    BioNTech Grp Mainz, Mainz, Germany..
    Mutanome engineered RNA immuno-therapy (MERIT) for patients with triple negative breast cancer2017In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 28, no suppl 11Article in journal (Other academic)
  • 20.
    Glimelius, B
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Oliveira, J
    Rectal cancer: ESMO clinical recommendations for diagnosis, treatment and follow-up2008In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 19 Suppl 2, p. ii31-2Article in journal (Other academic)
  • 21.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Adjuvant chemotherapy in rectal cancer: an issue or a nonissue?2010In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 21, no 9, p. 1739-1741Article in journal (Refereed)
  • 22.
    Glimelius, Bengt
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Lahn, M.
    Window-of-opportunity trials to evaluate clinical activity of new molecular entities in oncology2011In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 22, no 8, p. 1717-1725Article, review/survey (Refereed)
    Abstract [en]

    Background: The introduction of molecular targeted agents (e. g. monoclonal antibodies or kinase inhibitors) and cancer vaccines has raised the question whether alternate clinical trial designs, including window trials, are better suited to evaluate such new molecular entities (NMEs) and improve their approval rates. In window trials, patients receive an NME for a window of time before starting standard treatment allowing the evaluation of an NME in tumors unperturbed by previous therapies. Methods: A systematic literature search was conducted to identify window trials in adult and pediatric oncology. Results: Twenty-nine window trials were identified and reviewed, 13 in pediatric and 16 in adult oncology. Most of the trials (20/29) tested cytotoxics known to have activity in other clinical situations. In contrast to trials with pretreated patients, the window trials established the antitumor activity of melphalan, topotecan, epirubicin and etoposide in untreated patients with rhabdomyosarcoma or small-cell lung cancer. In window trials with ineffective or modestly active NMEs, we found no indication of a significant negative effect on overall survival for participating patients. Conclusions: Provided close safety monitoring and careful patient selection, window trials are a safe option to investigate potential clinical activity of NMEs.

  • 23.
    Glimelius, Bengt
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Lahn, M.
    Gawande, S.
    Cleverly, A.
    Darstein, C.
    Musib, L.
    Liu, Y.
    Spindler, K. L.
    Frödin, J-E.
    Berglund, Åke
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Byström, P.
    Qvortrup, C.
    Jakobsen, A.
    Pfeiffer, P.
    A window of opportunity phase II study of enzastaurin in chemonaive patients with asymptomatic metastatic colorectal cancer2010In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 21, no 5, p. 1020-1026Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Preclinically, protein kinase C and AKT activation can be inhibited by enzastaurin and reduce tumor growth of colorectal cancer cells. In asymptomatic patients with metastatic colorectal cancer (mCRC), enzastaurin activity was evaluated by measuring the 6-month progression-free survival (PFS) rate in a window study design. PATIENTS AND METHODS: Chemonaive patients with asymptomatic mCRC who did not require immediate chemotherapy-induced tumor reduction received a 400-mg thrice daily loading dose of enzastaurin on day 1 of cycle 1, followed by 500 mg once daily for the remaining 28-day cycles. Progression was assessed on the basis of radiographic imaging, rise in carcinoembryonic antigen or lactate dehydrogenase (LDH) levels or by appearance of clinical symptoms. RESULTS: Twenty-eight patients received daily enzastaurin. The 6-month PFS rate was 28% [95% confidence interval (CI) 13%-45%] and median PFS was 1.9 months (95% CI 1.8-4.5 months). Twelve (43%) patients had stable disease with a median duration of 6.1 months. The survival rate at 20 months was 77% (95% CI 47%-92%). No grade 4 toxicity was reported and grade 3 toxic effects were observed in three patients with one patient showing probable drug-related elevation of liver transaminases. CONCLUSION: The window design in asymptomatic patients with mCRC can be safely applied to assess the activity and safety of novel cytostatic agents like enzastaurin.

  • 24.
    Glimelius, Bengt
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Oliveira, J.
    Rectal cancer: ESMO clinical recommendations for diagnosis, treatment and follow-up2009In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, ISSN 1569-8041, Vol. 20, no Suppl 4, p. 54-6Article in journal (Refereed)
  • 25.
    Glimelius, Bengt
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Cervantes, A.
    Rectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up2010In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 21, no Suppl 5, p. v82-v86Article in journal (Refereed)
  • 26.
    Glimelius, Bengt
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Spindler, K. L.
    Frödin, J-E.
    Berglund, Åke
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Byström, P.
    Qvortrup, C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Jakobsen, A.
    Pfeiffer, P.
    Long-term follow-up of chemonaive patients with asymptomatic metastatic colorectal cancer treated with enzastaurin in a window of opportunity phase II study2010In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 21, no 5, p. 1127-1128Article in journal (Refereed)
  • 27.
    Glimelius, Bengt
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Sørbye, H
    Balteskard, L
    Byström, P
    Pfeiffer, P
    Tveit, K
    Heikkilä, R
    Keldsen, N
    Albertsson, M
    Starkhammar, H
    Garmo, H
    Berglund, Åke
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    A randomized phase III multicenter trial comparing irinotecan in combination with the Nordic bolus 5-FU and folinic acid schedule or the bolus/infused de Gramont schedule (Lv5FU2) in patients with metastatic colorectal cancer2008In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 19, no 5, p. 909-914Article in journal (Refereed)
    Abstract [en]

    Background: To compare irinotecan with the Nordic 5- fluorouracil (5- FU) and folinic acid (FA) bolus schedule [ irinotecan 180 mg/m(2) on day 1, 5- FU 500 mg/m(2) and FA 60 mg/m(2) on day 1 and 2 (FLIRI)] or the Lv5FU2 schedule [ irinotecan 180 mg/m(2) on day 1, FA 200 mg/m(2), 5- FU bolus 400 mg/m(2) and infused 5- FU 600 mg/m(2) on day 1 and 2 (Lv5FU2- IRI)] due to uncertainties about how to administrate 5- FU with irinotecan.

    Patients and methods: Patients (n = 567) with metastatic colorectal cancer were randomly assigned to receive FLIRI or Lv5FU2- IRI. Primary end point was progression- free survival (PFS).

    Results: Patient characteristics were well balanced. PFS did not differ between groups (median 9 months, P = 0.22). Overall survival (OS) was also similar (median 19 months, P = 0.9). Fewer objective responses were seen in the FLIRI group (35% versus 49%, P = 0.001) but the metastatic resection rate did not differ (4% versus 6%, P = 0.3). Grade 3/4 neutropenia (11% versus 5%, P = 0.01) and grade 2 alopecia (18% versus 9%, P = 0.002) were more common in the FLIRI group. The 60- day mortality was 2.4% versus 2.1%.

    Conclusions: Irinotecan with the bolus Nordic schedule (FLIRI) is a convenient treatment with PFS and OS comparable to irinotecan with the Lv5FU2 schedule. Neutropenia and alopecia are more prevalent, but both regimens are equally well tolerated.

  • 28.
    Glimelius, Bengt
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Tiret, E.
    Cervantes, A.
    Arnold, D.
    Rectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up2013In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 24, no Suppl. 6, p. 81-88Article in journal (Refereed)
  • 29.
    Granberg, Dan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Eriksson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Wilander, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Grimfjärd, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Fjällskog, Marie-Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Skogseid, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Experience in treatment of metastatic pulmonary carcinoid tumors2001In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 12, no 10, p. 1383-1391Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    The only cure for patients with pulmonary carcinoids is surgery. In the present paper, we report the results of medical treatment of patients with metastatic tumors, their circulating hormone markers, and immunohistochemical profile of the tumors. PATIENTS AND

    METHODS/RESULTS:

    The response to systemic antitumoral treatment was studied in 31 patients with metastatic pulmonary carcinoids. Median survival from treatment start was 25 months. Alpha-interferon treatment has resulted in stable disease in 4 of 27 patients (median duration 15 months), while 23 patients showed progressive disease. Somatostatin analogues given as single drug treatment resulted in progressive disease. Streptozotocin and 5-fluorouracil resulted in progressive disease in seven of seven patients. Stable disease was obtained for 8 and 10 months respectively in two of two patients treated with streptozotocin + doxorubicin. Two of eight patients treated with cisplatinum + etoposide showed a significant decrease in tumor size lasting six and eight months respectively, and one displayed stable disease for seven months. Elevation of plasma chromogranin A was seen in 93%.

    CONCLUSIONS:

    The results of systemic antitumoral treatment of pulmonary carcinoids with distant metastases are generally discouraging. Chemotherapy with cisplatinum + etoposide, or doxorubicin combined with streptozotocin or paclitaxel may be of value. Alpha-interferon and octreotide offer efficient symptomatic relief, but stabilizes tumor growth in merely 15% of the cases. Plasma chromogranin A is the most frequently elevated tumor marker.

  • 30.
    Gronowitz, Simon J.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Virology.
    Nisman, B.
    Peretz-Yablonski, T.
    Total cell division the ultimate biomarker for personalized medicine in cancer?: updated technology and novel clinical results2012In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 23, no S9, p. 88-88Article in journal (Other academic)
  • 31.
    Hagberg, Hans
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Blomkvist, E
    Pontén, Urban
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Persson, C
    Muhr, Carin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Eriksson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Olsson, Y
    Lilja, A
    Does alpha-interferon in conjunctions with radiotheraphy increase the risk of complications in the central nervous system?1990In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 1, no 6, p. 449-451Article in journal (Refereed)
  • 32.
    Hagman, H.
    et al.
    Cty Hosp Ryhov, Dept Oncol, S-55185 Jonkoping, Sweden..
    Frodin, J. -E
    Berglund, Åke
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Sundberg, J.
    Skane Univ Hosp, Dept Oncol, Lund, Sweden..
    Vestermark, L. W.
    Odense Univ Hosp, Dept Oncol, DK-5000 Odense, Denmark..
    Albertsson, M.
    Linkoping Univ Hosp, Dept Oncol, S-58185 Linkoping, Sweden..
    Fernebro, E.
    Vaxjo Hosp, Dept Oncol, Vaxjo, Sweden..
    Johnsson, A.
    Skane Univ Hosp, Dept Oncol, Lund, Sweden..
    A randomized study of KRAS-guided maintenance therapy with bevacizumab, erlotinib or metronomic capecitabine after first-line induction treatment of metastatic colorectal cancer: the Nordic ACT2 trial2016In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 27, no 1, p. 140-147Article in journal (Refereed)
    Abstract [en]

    Maintenance treatment (mt) with bevacizumab (bev) +/- erlotinib (erlo) has modest effect after induction chemotherapy in metastatic colorectal cancer (mCRC). We hypothesized the efficacy of erlo to be dependent on KRAS mutational status and investigated this by exploring mt strategies with bev +/- erlo and low-dose capecitabine (cap). Included patients had mCRC scheduled for first-line therapy, Eastern Cooperative Oncology Group (ECOG) 0-1 and no major comorbidities. Treatment with XELOX/FOLFOX or XELIRI/FOLFIRI + bev was given for 18 weeks. After induction, patients without progression were eligible for randomization to mt; KRAS wild-type (wt) patients were randomized to bev +/- erlo (arms wt-BE, N = 36 versus wt-B, N = 35), KRAS mutated (mut) patients were randomized to bev or metronomic cap (arms mut-B, N = 34 versus mut-C, N = 33). Primary end point was progression-free survival (PFS) rate (PFSr) at 3 months after start of mt. A pooled analysis of KRAS wt patients from the previous ACT study was performed. We included 233 patients. Median age was 64 years, 62% male, 68% ECOG 0, 52% with primary tumor in situ. A total of 138 patients started mt after randomization. PFSr was 64.7% versus 63.6% in wt-B versus wt-BE, P = 1.000; and 75% versus 66.7% in mut-B versus mut-C, P = 0.579, with no significant difference in median PFS and overall survival (OS). In the pooled cohort, median PFS was 3.7 months in wt-B (N = 64) and 5.7 months in wt-BE (N = 62) (hazard ratios 1.03, 95% confidence interval 0.70-1.50, P = 0.867). The frequency of any grade 3/4 toxicities during mt was: 28%/58%/18%/15% (wt-B/wt-BE/mut-B/mut-C). Addition of erlo to bev as mt in KRAS wt mCRC did not significantly improve PFS or OS, but it did increase toxicity. KRAS status does not seem to influence the outcome of treatment with erlotinib. Metronomic cap warrants further investigation in mt strategies, given our explorative results. NCT01229813.

  • 33.
    Hamfjord, J.
    et al.
    Oslo Univ Hosp, Oslo, Norway.
    Guren, T.
    Oslo Univ Hosp, Oslo, Norway.
    Dajani, O.
    Oslo Univ Hosp, Oslo, Norway.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Sorbye, H.
    Univ Bergen, Haukeland Univ Hosp, Bergen, Norway.
    Pfeiffer, P.
    Odense Univ Hosp, Dept Oncol, Odense, Denmark.
    Christoffersen, T.
    Univ Oslo, Oslo, Norway.
    Lingjaerde, O.
    Univ Oslo, Oslo, Norway.
    Tveit, K.
    Oslo Univ Hosp, Oslo, Norway.
    Kure, E.
    Oslo Univ Hosp, Oslo, Norway.
    Pallisgaard, N.
    Zealand Hosp, Roskilde, Denmark;Aarhus Univ Hosp, Dept Oncol, Aarhus, Denmark.
    Spindler, K.
    Total circulating cell-free DNA (cfDNA) as a prognostic biomarker in metastatic colorectal cancer prior to first-line oxaliplatin-based chemotherapy2018In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 29, no suppl 5, article id O - 026Article in journal (Other academic)
  • 34.
    Hoersch, D.
    et al.
    Zentralklin Bad Berka, Dept Internal Med, Bad Berka, Germany..
    Kulke, M. H.
    Dana Farber Canc Inst, Div Med Oncol Solid Tumor Oncol, Boston, MA 02115 USA..
    Caplin, M.
    Royal Free Hosp, Neuroendocrine Tumour Unit, London, England..
    Anthony, L.
    Univ Kentucky, Div Med Oncol, Chandler Med Ctr, Lexington, KY USA..
    Bergsland, E.
    UCSF Helen Diller Family Comprehens Canc Ctr, Hereditary GI Canc Prevent Program, San Francisco, CA USA..
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Warner, R. R. P.
    Icahn Sch Med Mt Sinai, Div Gastroenterol, New York, NY 10029 USA..
    Kunz, P.
    Stanford Univ, Med Ctr, Div Oncol, Stanford, CA 94305 USA..
    Grande Pulido, E.
    Hosp Univ Ramon y Cajal, Dept Med Oncol, Madrid, Spain..
    Valle, J. W.
    Univ Manchester, Dept Med Oncol, Christie, Manchester, Lancs, England..
    Dillon, J. S.
    Univ Iowa, Dept Internal Med Endocrinol & Metab, Iowa City, IA USA..
    Lapuerta, P.
    Lexicon Pharmaceut Inc, Lexicon Pharmaceut, The Woodlands, TX USA..
    Banks, P.
    Lexicon Pharmaceut Inc, Lexicon Pharmaceut, The Woodlands, TX USA..
    Jackson, S.
    Lexicon Pharmaceut Inc, Lexicon Pharmaceut, The Woodlands, TX USA..
    Pavel, M.
    Charite, Dept Gastroenterol & Hepatol Endocrinol & Metab D, Berlin, Germany..
    Efficacy and safety of telotristat ethyl in patients with carcinoid syndrome inadequately controlled by somatostatin analogs: Analysis of the completed TELESTAR extension period2017In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 28, no S5, article id 440PDArticle in journal (Other academic)
  • 35. Holte, H.
    et al.
    Leppa, S.
    Bjorkholm, M.
    Fluge, O.
    Jyrkkio, S.
    Delabie, J.
    Sundström, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Karjalainen-Lindsberg, M. -L
    Erlanson, M.
    Kolstad, A.
    Fossa, A.
    Ostenstad, B.
    Lofvenberg, E.
    Nordstrom, M.
    Janes, R.
    Pedersen, L. M.
    Anderson, H.
    Jerkeman, M.
    Eriksson, M.
    Dose-densified chemoimmunotherapy followed by systemic central nervous system prophylaxis for younger high-risk diffuse large B-cell/follicular grade 3 lymphoma patients: results of a phase II Nordic Lymphoma Group study2013In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 24, no 5, p. 1385-1392Article in journal (Refereed)
    Abstract [en]

    Background: Many patients with aggressive B-cell lymphomas and high clinical risk score still die of lymphoma after conventional R-CHOP chemoimmunotherapy. We hypothesized that intensified chemoimmunotherapy including systemic central nervous system (CNS) prophylaxis improves outcome and reduces the incidence of CNS-related events. Patients and methods: Inclusion criteria were age 18-65 years, primary diffuse large B-cell lymphoma or grade III follicular lymphoma without clinical signs of CNS disease and negative cerebrospinal fluid cytology, age-adjusted International Prognostic Index 2-3 and WHO performance score 0-3. Treatment consisted of six courses of R-CHOEP-14 followed by a course of high-dose cytarabine and a course of high-dose methotrexate. Primary end point was failure-free survival (FFS) at 3 years. Results: A total of 156 eligible patients with a median age of 54 years (range 20-64) were included. Three toxic deaths were observed. Three-year overall survival (OS) and FFS rates (median observation time 52 months for survivors) were 81% and 65%, respectively. Seven patients experienced CNS relapse, all within 6 months. Conclusions: The results are promising with favorable 3-year OS and FFS rates, a low toxic death rate and a lower than expected number of CNS events. CNS progression might be further reduced by earlier CNS prophylaxis. CinicalTrials.gov.identifier: NCT01502982.

  • 36. Horwich, A
    et al.
    Hugosson, J
    de Reijke, T
    Wiegel, T
    Fizazi, K
    Kataja, V
    Prostate cancer: ESMO Consensus Conference Guidelines 20122013In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 24, no 5, p. 1141-1162Article in journal (Refereed)
    Abstract [en]

    The first ESMO Consensus Conference on prostate cancer was held in Zurich, Switzerland, on 17-19 November 2011, with the participation of a multidisciplinary panel of leading professionals including experts in methodological aspects. Before the conference, the expert panel prepared clinically relevant questions about prostate cancer in four areas for discussion as follows: diagnosis and staging, management of early localized disease, management of advanced localized disease and systemic disease. All relevant scientific literature, as identified by the experts, was reviewed in advance. During the Consensus Conference, the panel developed recommendations for each specific question. The recommendations detailed here are based on an expert consensus after careful review of published data. All participants have approved this final update.

  • 37.
    Iveson, T.
    et al.
    Univ Hosp Southampton, Dept Med Oncol, Southampton, Hants, England..
    Kerr, R.
    Univ Oxford, Churchill Hosp, Oncol, Oxford, England..
    Saunders, M.
    Christie NHS Fdn Trust, Oncol, Manchester, Lancs, England..
    Hollander, N.
    Sygehus Syd Naestved, Oncology, Naestved, Denmark..
    Tabernero, J.
    VHIO, Med Oncol, Barcelona, Spain..
    Haydon, A.
    Alfred Hlth, Med Oncol, Melbourne, Vic, Australia..
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Harkin, A.
    Univ Glasgow, CRUK CTU, Glasgow, Lanark, Scotland..
    Scudder, C.
    Univ Oxford, Oncol, Oxford, England..
    Boyd, K.
    Univ Glasgow, CRUK CTU, Glasgow, Lanark, Scotland..
    Waterston, A.
    Beatson West Scotland Canc Ctr, Med Oncol, Glasgow, Lanark, Scotland..
    Medley, L.
    Dr Louise Medley, Oncol, London, England..
    Wilson, C.
    Addenbrookes Hosp, Cambridge Breast Unit, Cambridge, England..
    Ellis, R.
    Royal Cornwall Hosp, Oncol, Truro, England..
    Essapen, S.
    Royal Surrey Cty Hosp, St Lukes Canc Ctr, Oncol, Guildford, Surrey, England..
    Dhadda, A.
    Castle Hill Hosp, Oncol, Cottingham, England..
    Harrison, M.
    Mt Vernon Hosp, Oncol, Northwood, Middx, England..
    Falk, S.
    Bristol Haematol & Oncol Ctr, Oncol, Bristol, Avon, England..
    Abdel-Raouf, S.
    Queens Hosp, Oncol, Romford, Essex, England..
    Paul, J.
    Univ Glasgow, Inst Canc Sci, Canc Res UK Clin Trials Unit, Glasgow, Lanark, Scotland..
    Updated results of the SCOT study: An international phase III randomised (1:1) non-inferiority trial comparing 3 versus 6 months of oxaliplatin based adjuvant chemotherapy for colorectal cancer2017In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 28, no S5, article id LBA22Article in journal (Other academic)
  • 38. Johnsson, A.
    et al.
    Hagman, H.
    Frodin, J. -E
    Berglund, Åke
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Keldsen, N.
    Fernebro, E.
    Sundberg, J.
    Christensen, R. De Pont
    Spindler, K-L. Garm
    Bergstrom, D.
    Jakobsen, A.
    A randomized phase III trial on maintenance treatment with bevacizumab alone or in combination with erlotinib after chemotherapy and bevacizumab in metastatic colorectal cancer: the Nordic ACT Trial2013In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 24, no 9, p. 2335-2341Article in journal (Refereed)
    Abstract [en]

    Background: The main objective was to study the effect on progression-free survival (PFS) of adding erlotinib to bevacizumab as maintenance treatment following chemotherapy and bevacizumab as first-line treatment of metastatic colorectal cancer (mCRC). Patients and methods: Patients with untreated mCRC received doublet chemotherapy + bevacizumab during 18 weeks and those without tumor progression were eligible for randomization to bevacizumab + erlotinib (arm A) or bevacizumab alone (arm B), until progression or unacceptable toxic effect. Results: Of the 249 patients enrolled, 80 started maintenance treatment in arm A and 79 in arm B. The rate of any grade 3/4 toxic effect was 53% in arm A and 13% in arm B. Median PFS was 5.7 months in arm A and 4.2 months in arm B (HR = 0.79; 95% confidence interval 0.55-1.12; P = 0.19). Overall survival (OS) from start of induction chemotherapy was 26.7 months in the randomized population, with no difference between the two arms. Conclusions: The addition of erlotinib to bevacizumab as maintenance treatment after first-line chemotherapy in mCRC did not improve PFS significantly. On-going clinical and translational studies focus on identifying subgroups of patients that may benefit from erlotinib in the maintenance setting.

  • 39. Kaye, S. B.
    et al.
    Colombo, N.
    Monk, B. J.
    Tjulandin, S.
    Kong, B.
    Roy, M.
    Chan, S.
    Filipczyk-Cisarz, E.
    Hagberg, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Vergote, I.
    Lebedinsky, C.
    Parekh, T.
    Santabarbara, P.
    Park, Y. C.
    Nieto, A.
    Poveda, A.
    Trabectedin plus pegylated liposomal doxorubicin in relapsed ovarian cancer delays third-line chemotherapy and prolongs the platinum-free interval2011In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 22, no 1, p. 49-58Article in journal (Refereed)
    Abstract [en]

    Background: OVA-301 is a large randomized trial that showed superiority of trabectedin plus pegylated liposomal doxorubicin (PLD; CentoCor Ortho Biotech Products L. P., Raritan, NJ, USA). over single-agent PLD in 672 patients with relapsed ovarian cancer, particularly in the partially platinum-sensitive subgroup [platinum-free interval (PFI) of 6-12 months]. This superiority has been suggested to be due to the differential impact of subsequent (platinum) therapy. Patients and methods: A detailed analysis of subsequent therapies and survival outcomes in the overall population and in the subsets according to platinum sensitivity was therefore conducted. Results: Similar proportions of patients received subsequent therapy in each arm (76% versus 77%), including further platinum-based regimens (49% versus 55%). Patients in the trabectedin/PLD arm received subsequent chemotherapy at a later time (median delay 2.5 months versus PLD arm). Overall survival from subsequent platinum was significantly prolonged in the partially platinum-sensitive disease subset (hazard ratio = 0.63; P = 0.0357). Conclusion: The superiority of trabectedin/PLD over single-agent PLD in OVA-301 cannot be explained by differences in the extent or nature of subsequent therapies administered to these patients. On the other hand, these exploratory analyses support the hypothesis that the enhanced survival benefits in the partially platinum-sensitive subset might be due to an extended PFI leading to longer survival with subsequent platinum.

  • 40.
    Khan, Tanweera Shaheena
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Imam, Hassan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Juhlin, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Skogseid, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Gröndal, Staffan
    Tibblin, Sten
    Wilander, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology, Molecular and Morphological Pathology.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Eriksson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Streptozocin and o,p'DDD in the treatment of adrenocortical cancer patients: long-term survival in its adjuvant use2000In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 11, no 10, p. 1281-1287Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    To evaluate the efficacy of streptozocin and o.p'DDD (SO) in adrenocortical cancer (ACC) patients since other chemotherapeutic regimens have limited effects.

    PATIENTS AND METHODS:

    We performed a phase II study with SO therapy in 40 ACC patients (median age 44 years). Oral o,p'DDD administration (1-4 g/d, every day) was given together with intravenous streptozocin (1 g/d for five days, thereafter 2 g once every three weeks). 5HT3-receptor blocker was used as standard premedication for streptozocin.

    RESULTS:

    The SO therapy was found to have significant effects on disease-free interval (P = 0.02) as well as on survival (P = 0.01) in adjuvantly treated cases (n = 17) in comparison to the patients who did not get any therapy after complete resection (n = 11). Complete or partial response was obtained in 36.4% of patients with measurable disease (n = 22). The overall two-year and five-year survival rates were 70% and 32.5%, respectively. The presence of metastases at diagnosis was identified as a poor prognostic factor (P = 0.02).

    CONCLUSIONS:

    The present study necessitates further randomized clinical study of SO therapy in the treatment of ACC, mainly as adjuvant treatment immediately after curative intended surgery, and could be developed into a regular treatment regimen.

  • 41.
    Kulke, M.
    et al.
    Dana Farber Canc Inst, Med Oncol, Boston, MA 02115 USA..
    Hoersch, D.
    Zent Klin Bad Berka GmbH, Ctr Neuroendocrine Tumors Bad Berka, Gastroenterol & Endocrinol, Bad Berka, Germany..
    Caplin, M.
    Royal Free Hosp, Sch Med, Gastroenterol & Neuroendocrine Tumours, London, England..
    Anthony, L.
    Univ Kentucky, Med Oncol, Lexington, KY USA..
    Bergsland, E.
    UCSF Helen Diller Family Comprehens Canc Ctr, Hematol Oncol, San Francisco, CA USA..
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Welin, Staffan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine oncology.
    Warner, R.
    Mt SInai Med Coll, Gastroenterol, New York, NY USA..
    Bohas, C. Lombard
    Hop Edouard Herriot, Med Oncol, Pav E Bis, Lyon, France..
    Kunz, P. L.
    Stanford Univ, Sch Med, Med Oncol, Palo Alto, CA 94304 USA..
    Grande, E.
    Hosp Univ Ramon & Cajal, Med Oncol, Madrid, Spain..
    Valle, J. W.
    Univ Manchester, Christie NHS Fdn Trust, Med Oncol, Manchester, Lancs, England..
    Lapuerta, P.
    Lexicon Pharmaceut, Med Affairs, The Woodlands, TX USA..
    Banks, P.
    Lexicon Pharmaceut, Med Affairs, The Woodlands, TX USA..
    Jackson, S.
    Lexicon Pharmaceut Inc, Clin Operat, The Woodlands, TX USA..
    Jiang, W.
    Lexicon Pharmaceut, Med Affairs, The Woodlands, TX USA..
    Biran, T.
    Lexicon Pharmaceut Inc, Clin Operat, The Woodlands, TX USA..
    Pavel, M.
    Charite, Endocrinol, Berlin, Germany..
    Integrated placebo-controlled safety analysis from clinical studies of telotristat ethyl for the treatment of carcinoid syndrome2016In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 27, no suppl. 6, article id 422PDArticle in journal (Refereed)
  • 42.
    Lapuerta, P.
    et al.
    Lexicon Pharmaceut Inc, The Woodlands, TX USA..
    Kulke, M. H.
    Dana Farber Canc Inst, Gastrointestinal Canc Treatment Ctr, Boston, MA 02115 USA..
    Caplin, M.
    Royal Free Hosp, Neuroendocrine Tumour Unit, London, England..
    Bergsland, E.
    UCSF Helen Diller Family Comprehens Canc Ctr, Hereditary GI Canc Prevent Program, San Francisco, CA USA..
    Anthony, L.
    Univ Kentucky, Chandler Med Ctr, Div Med Oncol, Lexington, KY USA..
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Pavel, M.
    Charite, Dept Gastroenterol & Hepatol Endocrinol & Metab D, Berlin, Germany..
    Hoersch, D.
    Zentralklin Bad Berka, Dept Internal Med, Bad Berka, Germany..
    O'Dorisio, T. M.
    Univ Iowa, Dept Internal Med Endocrinol & Metab, Iowa City, IA USA..
    Dillon, J. S.
    Univ Iowa, Dept Internal Med Endocrinol & Metab, Iowa City, IA USA..
    Kassler-Taub, K.
    Lexicon Pharmaceut Inc, The Woodlands, TX USA..
    Jiang, W.
    Lexicon Pharmaceut Inc, The Woodlands, TX USA..
    Long-term survival of patients with carcinoid syndrome in clinical trials of telotristat ethyl2017In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 28, no S5, article id 442PArticle in journal (Other academic)
  • 43.
    Larsson, Gunnel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Sjödén, Per-Olow
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    von Essen, Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences.
    Importance-satisfaction discrepancies are associated with health-related quality of life in five-year survivors of endocrine gastrointestinal tumours1999In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 10, no 11, p. 1321-1327Article in journal (Refereed)
    Abstract [en]

    Background: Little is known about the health-related-quality of life (HRQoL) of patients with endocrine gastrointestinal tumours. In this study, HRQoL was investigated in long-term survivors of endocrine GI tumours.

    Patients and methods: A questionnaire including the EORTC QLQ-C30 and ratings of importance of and satisfaction with a variety of HRQoL aspects was mailed to patients with carci-noid tumours (n = 64), or endocrine pancreatic tumours (EPT, n = 55). Median time since diagnosis was 120 months (range 60–360). The majority of patients (77 of 119) had ongoing treatment.

    Results: The EORTC QLQ-C30 ratings suggest that in spite of a long disease duration and treatment, patients perceived their HRQoL as relatively good. There were no major differences in HRQoL ratings between patients with carcinoid tumours and those with EPT. Patients whose ratings of importance was higher than their ratings of satisfaction with a specific HRQoL aspect also evidenced a low HRQoL for that aspect.

    Conclusions: The results indicate that survivors of endocrine GI tumours enjoy a relatively good HRQoL and suggest that importance < satisfaction discrepancies identify patients with a low quality of life.

  • 44.
    Liljefors, Maria
    et al.
    Karolinska Univ Hosp Radiumhemmet, Dept Oncol, Stockholm, Sweden..
    Mozaffari, F. S.
    Karolinska Univ Hosp Radiumhemmet, Dept Oncol, Stockholm, Sweden..
    Mellstedt, H.
    Karolinska Univ Hosp Radiumhemmet, Dept Oncol, Stockholm, Sweden..
    Ullenhag, Gustav
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Immunomodulatory effects of lenalidomide in combination with gemcitabine as first-line treatment in patients with advanced pancreatic cancer2015In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 26, p. 12-12Article in journal (Other academic)
  • 45.
    Mattsson, Elisabet
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Psychosocial oncology and supportive care.
    El-Khouri, Bassam
    Ljungman, Gustaf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    von Essen, Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Psychosocial oncology and supportive care.
    Empirically derived psychosocial states among adolescents diagnosed with cancer during the acute and extended phase of survival2009In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 20, no 10, p. 1722-1727Article in journal (Refereed)
    Abstract [en]

    Patients and methods: Participants completed the Hospital Anxiety and   Depression Scale and two subscales, Vitality and Mental Health, in the   SF-36 4-8 weeks (T1) (n = 61), 6 (T2) (n = 57), 12 (T3) (n = 50), and   18 (T4) months (n = 48) after diagnosis. I-State as Object of Analysis   was used to identify a finite set of states based on three dimensions.   Cluster analysis was carried out using Ward's method.   Results: Five states were obtained: psychosocial dysfunction (state A)   and poor (B), incomplete (C), good (D), and excellent (E) psychosocial   function. At T1, more adolescents than expected by chance were in   states A (P < 0.05) and C (P < 0.01) and fewer in states D (P < 0.05)   and E (P < 0.001). At T4, more adolescents than expected by chance were   in state E (P < 0.001) and fewer in state C (P < 0.05). Female gender   and being in late adolescence when diagnosed is related to worse   psychosocial function.   Conclusion: The findings provide support for subgroups of adolescents   whose level of vitality, mental health, and anxiety differ during the   acute and extended phase of survival of cancer. Clinical interventions   tailored to the level of impairment as determined by the clusters may   result in better psychosocial outcomes.

  • 46.
    Mörth, Charlott
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Valachis, Antonis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Abu Sabaa, Amal
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Hedström, Gustaf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Flogegard, Max
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Enblad, Gunilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Does the omission of vincristine affect outcome and survival in patients with diffuse large B-cell lymphoma?2017In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 28, no S5, article id 1006PDArticle in journal (Other academic)
  • 47. Nilsson, Per J.
    et al.
    Rubio, C.
    Lenander, C.
    Auer, G.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Tumour budding detected by laminin-5 {gamma}2-chain immunohistochemistry is of prognostic value in epidermoid anal cancer2005In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 16, no 6, p. 893-8Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Markers for guidance with regard to individual prognosis and treatment planning are sought in epidermoid anal cancer. This study assessed the prognostic and predictive value of tumour budding. PATIENTS AND METHODS: From a population-based consecutive series of patients who were prospectively recorded, it was possible to investigate 209 (76%) of the pretreatment biopsies. Immunohistochemistry with a monoclonal antibody for the gamma2 chain of laminin-5 was used to detect tumour budding (defined as dissociated single cancer cells or clusters of up to five cells). RESULTS: Tumour budding was detected in 104 (50%) of the 209 samples. No significant correlation was found between tumour budding and clinicopathological characteristics. Patients with tumour budding had a statistically significantly better 5-year overall survival rate compared with patients lacking tumour budding (74% versus 64%, P <0.05). Albeit not statistically significant, other outcome variables such as tumour-specific survival, recurrence after initial complete response and rate of distant metastases, were all in favour of patients with tumour budding. Multivariate analysis reveals tumour budding as an independent positive prognostic factor. CONCLUSIONS: Tumour budding detected by laminin-5 immunohistochemistry may be of prognostic value in the treatment of epidermoid anal cancer. However, further studies are needed to clarify the possible clinical implications.

  • 48. Nordlinger, B.
    et al.
    Van Cutsem, E.
    Gruenberger, T.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Poston, G.
    Rougier, P.
    Sobrero, A.
    Ychou, M.
    Combination of surgery and chemotherapy and the role of targeted agents in the treatment of patients with colorectal liver metastases: recommendations from an expert panel2009In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 20, no 6, p. 985-992Article, review/survey (Refereed)
    Abstract [en]

    The past 5 years have seen the clear recognition that the administration of chemotherapy to patients with initially unresectable colorectal liver metastases can increase the number of patients who can undergo potentially curative secondary liver resection. Coupled with this, recent data have emerged that show that perioperative chemotherapy confers a disease-free survival advantage over surgery alone in colorectal cancer (CRC) patients with initially resectable liver disease. The purpose of this paper is to build on the existing knowledge and review the issues surrounding the use of chemotherapy +/- targeted agents combined with surgery in the treatment of CRC patients with liver metastases, with a view to providing clinical recommendations. An international panel of 21 experts in colorectal oncology comprising liver surgeons and medical oncologists reviewed the available evidence. In a major change to clinical practice, the panel's recommendation was that the majority of patients with CRC liver metastases should be treated up front with chemotherapy, irrespective of the initial resectability status of their metastases.

  • 49. Nordlinger, Bernard
    et al.
    Sorbye, Halfdan
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Poston, Graeme John
    Schlag, Peter M.
    Rougier, Philippe
    Bechstein, Wolf
    Primrose, John Neil
    Walpole, Euan Thomas
    Finch-Jones, Meg
    Jaeck, Daniel
    Mirza, Darius
    Parks, Rowan W.
    Collette, Laurence
    Praet, Michel
    Van Cutsem, Eric
    Scheithauer, Werner
    Mauer, Murielle E.
    Gruenberger, Thomas
    Long term survival data from EORTC study 40983: Perioperative chemotherapy for resectable liver metastases from colorectal cancer2012In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 23, p. 18-18Article in journal (Other academic)
  • 50. Nyren, O.
    et al.
    Lambe, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Ye, W.
    Adami, H. -O
    Are cohort data on smokeless tobacco use and pancreatic cancer confounded by alcohol use?2011In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 22, no 8, p. 1930-U4Article in journal (Refereed)
123 1 - 50 of 106
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