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  • 1. Al Hashmi, S.
    et al.
    Sadeghi, B.
    Hassan, Z.
    Abedi-Valugerdi, M.
    Lindskog, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Hassan, M.
    Omega-3 from fish oil augments GVHD through the enhancement of chemotherapy conditioning regimen and selective FoxP3 depletion2013In: Bone Marrow Transplantation, ISSN 0268-3369, E-ISSN 1476-5365, Vol. 48, no 6, p. 843-848Article in journal (Refereed)
    Abstract [en]

    Omega-3 is known to enhance the effects of several chemotherapeutic agents and to exert several immunoregulatory actions In the present study, we evaluated the effects of a 21-day feeding regimen with omega-3-rich fish oil (FO) and its corresponding control, omega-6 rich corn oil (CO), on the BU-CY conditioning and the development of GVHD after BMT in mice. Before conditioning, FO, but not CO, feeding caused a significant attenuation in the number and functionality of splenic FoxP3+ T regulatory cells (Treg). FO feeding also enhanced the effects of the conditioning through severe depletion of Treg cells in the spleen and CD11b+ myeloid cells in both the BM and spleen. Consequently, FO-fed animals conditioned with BU-CY showed exacerbated GVHD following transplantation with allogeneic BM and splenic cells. In contrast, identical transplantation in CO-fed mice resulted in poor engraftment and body weight loss. Moreover, in standard-fed recipients, BMT with cells from FO-fed donors resulted in moderate GVHD and improved the survival time, whereas BMT with cells from CO-fed donors shortened the survival time and caused anemia. We conclude that food supplements should be considered in patients undergoing BMT and/or chemotherapy treatment.

  • 2.
    Elmstedt, Sixten
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Mogensen, Hanna
    Karolinska Inst, Inst Environm Med, Unit Epidemiol, Stockholm, Sweden.
    Hallmans, Dan-Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Tavelin, Björn
    Umea Univ, Dept Radiat Sci, Umea, Sweden.
    Lundström, Staffan
    Karolinska Inst, Stockholms Sjukhem Fdn, Stockholm, Sweden;Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden.
    Lindskog, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Cancer patients hospitalised in the last week of life risk insufficient care quality - a population-based study from the Swedish Register of Palliative Care2019In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 58, no 4, p. 432-438Article in journal (Refereed)
    Abstract [en]

    Background: One-quarter of all cancer deaths in Sweden occur in hospitals. If the place of death affects the quality of end-of-life (EOL) is largely unknown.

    Methods: This population-based, retrospective study included all adults cancer deaths reported to the Swedish Register of Palliative Care in 2011-2013 (N = 41,729). Hospital deaths were compared to deaths occurring in general or specialised palliative care, or in nursing homes with respect to care quality indicators in the last week of life. Odds ratios (OR) with 95% confidence intervals (CI) were calculated with specialised palliative home care as reference.

    Results: Preferred place of death was unknown for 63% of hospitalised patients and consistent with the actual place of death in 25% compared to 97% in palliative home care. Hospitalised patients were less likely to be informed when death was imminent (OR: 0.3; CI: 0.28-0.33) as were their families (OR: 0.51; CI: 0.46-0.57). Validated screening tools were less often used in hospitals for assessment of pain (OR: 0.32; CI: 0.30-0.34) or other symptoms (OR: 0.31; CI: 0.28-0.34) despite similar levels of EOL symptoms. Prescriptions of as needed drugs against anxiety (OR: 0.27; CI: 0.24-0.30), nausea (OR: 0.19; CI: 0.17-0.21), or pulmonary secretions (OR: 0.29; CI: 0.26-0.32) were less prevalent in hospitals. Bereavement support was offered after 57% of hospital deaths compared to 87-97% in palliative care units and 72% in nursing homes.

    Conclusions: Dying in hospital was associated with inferior end-of-life care quality among cancer patients in Sweden.

  • 3.
    Lindskog, Magnus
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine.
    Karvestedt, Lars
    Furst, Carl Johan
    Glycaemic control in end-of-life care: fundamental or futile?2014In: Current Opinion in Supportive and Palliative Care, ISSN 1751-4258, Vol. 8, no 4, p. 378-382Article, review/survey (Refereed)
    Abstract [en]

    Purpose of review Diabetes mellitus is one of the most common comorbidities in palliative care. Yet, the optimal handling of diabetes mellitus in dying patients is debated. This review aims to discuss comprehensively the scientific basis as of today for diabetes mellitus management decisions in end-of-life (EOL) care. Recent findings Glycaemic control provides prognostic information in EOL care of diabetes mellitus patients. Original data on how to manage dying patients with type 2 diabetes mellitus are scarce. Findings in elderly type 2 diabetes mellitus patients and expert opinions support that glycaemic control should be relaxed in dying patients with type 2 diabetes mellitus, in the absence of risk factors for true insulin dependence, to avoid symptomatic hypoglycaemia. For terminal but conscious type 1 diabetes mellitus patients, regular blood glucose measurements and continued insulin therapy is the mainstay, with some discrepancy in preferred management between palliative care physicians and diabetes consultants. No randomized controlled trials are available. Improvement is clearly needed with regard to communication about diabetes mellitus in EOL and documentation of decisions. Corticosteroid-induced diabetes mellitus is a significant problem in palliative care, but predictors exist. Summary In the absence of large observational studies or randomized controlled trials, the current body of knowledge is based on expert opinions, surveys and retrospective studies. Nevertheless, some clinically meaningful recommendations can be made. Prospective studies need to be performed in order to improve our understanding about diabetes mellitus management in EOL. The palliative care community has a joint responsibility to address these questions.

  • 4.
    Lindskog, Magnus
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Wahlgren, Thomas
    Pfizer AB, Sollentuna, Sweden..
    Sandin, Rickard
    Pfizer AB, Sollentuna, Sweden..
    Kowalski, Jan
    JK Biostat AB, Stockholm, Sweden..
    Jakobsson, Maria
    Pfizer AB, Sollentuna, Sweden..
    Lundstam, Sven
    Univ Gothenburg, Sahlgrenska Univ Hosp, Dept Urol, Gothenburg, Sweden.;Univ Gothenburg, Sahlgrenska Acad, Gothenburg, Sweden..
    Ljungberg, Borje
    Umea Univ, Dept Surg & Perioperat Sci Urol & Androl, Umea, Sweden..
    Harmenberg, Ulrika
    Karolinska Univ Hosp, Dept Oncol Pathol, Stockholm, Sweden.;Karolinska Inst, Stockholm, Sweden..
    Overall survival in Swedish patients with renal cell carcinoma treated in the period 2002 to 2012: Update of the RENCOMP study with subgroup analysis of the synchronous metastatic and elderly populations2017In: Urologic Oncology, ISSN 1078-1439, E-ISSN 1873-2496, Vol. 35, no 9, article id 541.e15Article in journal (Refereed)
    Abstract [en]

    Background: This retrospective study investigated overall survival (OS) and factors influencing OS in Swedish patients with metastatic renal cell carcinoma (mRCC) during the pre- (2002-2005), early (2006-2008), and late (2009-2012) targeted therapy (TT) era. Methods: Three national Swedish registries identified patients with mRCC. Median OS was estimated using the Kaplan-Meier method. Multivariate analysis was performed using Cox proportional hazards regression. Subgroup analysis was conducted for patients with synchronous metastases (Ml) and the elderly (aged >= 75 y). Results: A total of 4,217 patients with mRCC were identified, including 1,533 patients with Ml and 1,275 elderly patients. For patients with mRCC diagnosed in 2002 to 2005, 2006 to 2008, and 2009 to 2012, median OS was 10.0, 13.0, and 18.0 months. Similarly, median OS improved in the M1 and elderly populations. Elderly patients were less likely to be prescribed TT (>= 75 vs. <75 y): 18.3 vs. 63.5% (in 2006-2008) and 28.6% vs. 55.9% (in 2009-2012). Diagnosis of mRCC in 2009 to 2012, nephrectomy and TT prescription were associated with improved OS in the total mRCC, Ml, and elderly populations. Conclusion: This real-world study showed continued significant improvement in mRCC OS during the late TT era, including in Ml and elderly populations. TT should be considered for all patients with mRCC based on tolerability, regardless of age.

  • 5.
    Lindskog, Magnus
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Wahlgren, Thomas
    Sandin, Rickard
    Kowalski, Jan
    Jakobsson, Maria
    Lundstam, Sven
    Ljungberg, Borje
    Harmenberg, Ulrika
    Overall survival (OS) in Swedish RCC patients treated 2000-2012: Update of the RENCOMP study2015In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 33, no 7, article id 413Article in journal (Other academic)
  • 6.
    Lynoe, Niels
    et al.
    Karolinska Inst, Stockholm Ctr Healthcare Eth, S-17177 Stockholm, Sweden..
    NattochDag, Sara
    Karolinska Univ Hosp, Stockholm, Sweden..
    Lindskog, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Juth, Niklas
    Karolinska Inst, Stockholm Ctr Healthcare Eth, S-17177 Stockholm, Sweden..
    Heed or disregard a cancer patient's critical blogging?: An experimental study of two different framing strategies2016In: BMC Medical Ethics, ISSN 1472-6939, E-ISSN 1472-6939, Vol. 17, article id 30Article in journal (Refereed)
    Abstract [en]

    Background: We have examined healthcare staff attitudes of toward a blogging cancer patient who publishes critical posts about her treatment and their possible effect on patient-staff relationships and treatment decisions.

    Methods: We used two versions of a questionnaire containing a vignette based on a modified real case involving a 39-year-old cancer patient who complained on her blog about how she was encountered and the treatment she received. Initially she was not offered a new, and expensive treatment, which might have influenced her perception of further encounters. In one version of the vignette, the team decides to put extra effort into both encounters and offers the expensive new cancer treatment. In the other version, the team decides to follow the clinic's routine to the letter. Subsequently, blog postings became either positive or negative in tone. We also divided participants into value-neutral and value-influenced groups (regarding personal values) by asking how their trust in healthcare would be affected if the team's suggestion were followed.

    Results: A total of 56 % (95 % CI: 51-61) of the respondents faced with a team decision to 'do something-extra' in encounters would act in accordance with this ambition. Concerning treatment, 32 % (95 % CI: 28-38) would follow the team's decision to offer a new and expensive treatment. A large majority of those who received the "follow-routine" version agreed to do so in encountering [94 % (95 % CI: 91-97)]. Similar proportions were found regarding treatment [86 % (95 % CI: 82-90)]. A total of 83 % (95 % CI: 76-91) of the value-neutral participants who received the "do-something-extra" version stated that they would act as the team suggested regarding encounters, while 57 % (95 % CI: 47-67) would do so in regard to treatment. Among the value-influenced participants who received the "do-something-extra" version, 45 % (95 % CI: 38-51) stated that they would make an extra effort to accommodate the patient and her needs, while the proportion for treatment was 22 % (95 % CI: 16-27). Among those who had received the "follow-routine" version, a large majority agreed, and no difference was indicated between the value-neutral and the value-influenced participants.

    Conclusion: The present study indicates that healthcare staff is indeed influenced by reading a patient's critical blog entries, largely regarding encounters, but also concerning treatment is concerned. Value-neutral healthcare personnel seem to exhibit a pragmatic attitude and be more inclined to heed and respond to a patient whose criticism may well be warranted. The study also indicates that healthcare staff is partly positive or negative to future blogging patients depending on how the issue has been framed. For future research we suggest as a bold hypothesis that the phrase "clinical routine" might conceal power aspects masquerading as adopted ethical principles.

  • 7.
    Redig, Josefine
    et al.
    ICON, Stockholm, Sweden.
    Dalen, Johan
    ICON, Stockholm, Sweden.
    Harmenberg, Ulrika
    Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden.
    Lindskog, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Ljungberg, Borje
    Umeå Univ, Dept Surg & Perioperat Sci, Urol & Androl, Umeå, Sweden.
    Lundstam, Sven
    Sahlgrens Univ Hosp, Dept Urol, Gothenburg, Sweden.
    Sandin, Rickard
    Pfizer AB, Sollentuna, Sweden.
    Wahlgren, Thomas
    Pfizer AB, Sollentuna, Sweden.
    Akerborg, Orjan
    ICON, Stockholm, Sweden.
    Jakobsson, Maria
    Pfizer AB, Sollentuna, Sweden.
    Real-world cost-effectiveness of targeted therapy in metastatic renal cell carcinoma in Sweden: a population-based retrospective analysis2019In: Cancer Management and Research, ISSN 1179-1322, Vol. 11, p. 1289-1297Article in journal (Refereed)
    Abstract [en]

    Objective: To explore cost-effectiveness of targeted therapies (TTs) in the treatment of metastatic renal cell carcinoma (mRCC) in a real-world context using a nationwide population-based approach.

    Methods: Data on patients diagnosed with mRCC between 2002 and 2012 were extracted from Swedish national health data registers. To facilitate comparisons of patients diagnosed before and after TT introduction to the market, three cohorts were derived: pre-TT introduction (preTT), patients diagnosed 2002–2005; early TT introduction (TTi), patients diagnosed 2006–2008; and late TT introduction (TTii), which was limited to patients diagnosed 2009–2010 to ensure availability of total health care resource utilization (HCRU) data. Patients were followed until end of 2012. The value of TTs across cohorts was estimated using mean HCRU costs per life-year (LY) gained. Data on HCRU were obtained through national health registers for dispensed medication and inpatient and outpatient care, and the associated costs were estimated using the Lin method to account for censoring. LYs gained were defined as the difference in mean survival over the study period.

    Results: The preTT, TTi, and TTii cohorts consisted of 1,366, 1,158, and 806 patients, respectively. Mean survival in years from mRCC diagnosis was 1.45 in the preTT cohort, 1.62 in the TTi cohort, and 1.83 in the TTii cohort. The respective mean total HCRU cost per patient over the study period was US$16,894, US$29,922, and US$30,037. The cost per LY gained per cohort was US$78,656 for TTi vs preTT, US$34,132 for TTii vs preTT, and US$523 for TTii vs TTi.

    Conclusion: Given common willingness-to-pay per LY gained thresholds, this study in a real-world population suggests the use of TTs in the Swedish mRCC population is increasingly cost-effective over time.

  • 8.
    Stenman, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Benmakhlouf, Hamza
    Department of Medical Radiation Physics and Nuclear Medicine, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
    Wersäll, Peter
    Department of Oncology-Pathology, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
    Hatiboglu, Mustafa Aziz
    Department of Neurosurgery, Bezmialem Vakif University Medical School, Istanbul, Turkey.
    Silva, Julieta Mayer
    Centro Gamma Knife, CUF Infante Santo Hospital, Lisbon, Portugal.
    Harmenberg, Ulrika
    Department of Oncology-Pathology, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
    Lindskog, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Sinclair, Georges
    Department of Neurosurgery, Bezmialem Vakif University Medical School, Istanbul, Turkey. Department of Neurosurgery, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden..
    Albumin, corticosteroid use and Karnofsky performance status predict outcome of single-fraction gamma knife radiosurgery in clear cell renal cell carcinoma patients with brain metastasesManuscript (preprint) (Other academic)
    Abstract [en]

    Background and Purpose: To evaluate the effects of single fraction gamma knife radiosurgery (sf-GKRS) on patients with renal cell carcinoma (RCC) brain metastases (BM) in the era of targeted agents (TA).

    Material and Methods: Clear cell metastatic RCC patients treated with sf-GKRS due to BM in 2005-2014 at three European centres were retrospectively analysed (n=43). Median follow-up was 56 months. Ninety-five percent had prior nephrectomy, 53% synchronous metastasis and 86% extracranial disease at first sf-GKRS. Karnofsky performance status (KPS) ranged from 60-100%.  Outcome measures were overall survival (OS), local control (LC) and adverse radiation effects (ARE).

    Results: One hundred and ninety-four targets were irradiated. Median number of targets at first sf-GKRS were two. The median prescription dose was 22 Gy. Thirty-seven percent had repeated sf-GKRS. Eighty-eight percent received TA. LC at 12 and 18 months were 97% and 90%. Median OS from first sf-GKRS was 15.7 months. Serum albumin (HR 5.3), corticosteroids pre sf-GKRS (HR 5.8) and KPS (HR 9.1) were independent prognostic factors. MSKCC risk group, synchronous metastasis, age, number of BM or extracranial metastases provided no additional prognostic information. Other prognostic scores for BM radiosurgery, including DS-GPA, Renal-GPA, LLV-SIR and CITV-SIR, did not add prognostic value. ARE were seldom symptomatic and were associated with tumour volume, 10-Gy volume and pre-treatment perifocal oedema. ARE were less common among patients treated with TA within one month of sf-GKRS.

    Conclusions: We identified three independent prognostic factors with potential impact on clinical decision making in patients with clear cell RCC BM.

  • 9.
    Stenman, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Laurell, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Lindskog, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Prognostic significance of serum albumin in patients with metastatic renal cell carcinoma2014In: Medical Oncology, ISSN 1357-0560, E-ISSN 1559-131X, Vol. 31, no 3, p. 841-Article in journal (Refereed)
    Abstract [en]

    Systemic inflammation has been suggested to impact on the prognosis of metastatic renal cell carcinoma (mRCC). We undertook a retrospective analysis of patients with mRCC treated at Akademiska University Hospital in Sweden during the years 2005-2012 to assess the possible prognostic significance of inflammation-related factors including serum albumin, platelet count, weight loss and C-reactive protein (CRP). The Memorial Sloan-Kettering Cancer Center (MSKCC) criteria for prognosis of mRCC and ECOG performance status were assessed for all patients. Overall survival (OS) and progression-free survival (PFS) were calculated according to Kaplan-Meier, and Cox proportional hazards regression was used for uni- and multivariate analyses. The median OS of all patients (n=84) was 20 months. Univariate analysis identified low serum albumin (HR=4.17, p<0.001), elevated platelet count (HR=2.98, p<0.001) and patient-reported weight loss prior to diagnosis of mRCC (HR=2.73, p<0.001), in addition to MSKCC (HR=3.35, p=0.0088) to be associated with shorter OS. CRP did not significantly affect OS. Serum albumin retained prognostic significance for OS in multivariate analysis (HR=2.72, p=0.015). In patients treated with an angiogenesis-targeted agent (n=47), low serum albumin level (HR=4.63, p<0.001) and elevated platelet count (HR=2.11, p=0.022) were associated with shorter PFS. In contrast, CRP, weight loss and MSKCC risk group did not significantly affect PFS. In multivariate analysis serum albumin remained associated with PFS (HR=3.92, p=0.0035). Our findings identify serum albumin as an independent prognostic factor for patients with mRCC treated with angiogenesis-targeted therapy.

  • 10.
    Stenman, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Nearchou, Andreas Demetrios
    Karolinska Inst, Dept Oncol & Pathol, Stockholm, Sweden.
    Sandström, Per
    Karolinska Inst, Dept Oncol & Pathol, Stockholm, Sweden.
    Lindskog, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Harmenberg, Ulrika
    Karolinska Inst, Dept Oncol & Pathol, Stockholm, Sweden.
    Metastatic papillary renal cell carcinoma: A retrospective study from two large academic centers in Sweden2016In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 34, no 2Article in journal (Other academic)
  • 11.
    Stenman, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Sinclair, G.
    Karolinska Inst, Dept Neurosurg, S-17176 Stockholm, Sweden;Karolinska Univ Hosp, S-17176 Stockholm, Sweden.
    Paavola, P.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Wersall, P.
    Karolinska Univ Hosp, S-17176 Stockholm, Sweden;Karolinska Inst, Dept Oncol Pathol, S-17176 Stockholm, Sweden.
    Harmenberg, U.
    Karolinska Univ Hosp, S-17176 Stockholm, Sweden;Karolinska Inst, Dept Oncol Pathol, S-17176 Stockholm, Sweden.
    Lindskog, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Overall survival after stereotactic radiotherapy or surgical metastasectomy in oligometastatic renal cell carcinoma patients treated at two Swedish centres 2005-20142018In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 127, no 3, p. 501-506Article in journal (Refereed)
    Abstract [en]

    Background and purpose: Investigate effects of stereotactic radiotherapy (SRT) or surgical metastasectomy (SM) on overall survival (OS) in metastatic renal cell carcinoma (mRCC) in the era of targeted agents (TA).

    Material and methods: mRCC patients (n = 117) treated with SRT (n = 57), SM (n = 30) or both modalities sequentially (n = 30) at two oncological centres in Sweden in 2005-2014 were retrospectively included. Median follow-up (mFU) was 63 months.

    Results: A majority had clear cell histology, 1-3 metastases, and ECOG performance status of 0 or 1. Two thirds had intermediate or poor risk and 44% synchronous metastases. 65% received TA. SRT patients were more likely to have adverse risk profiles. Median OS was 51 months without significant differences between SRT and SM. ECOG 1 vs 0 (HR 2.9; CI 1.6-5.2; p < 0.001), intracranial targets (HR 1.8; CI 1.1-3.2; p = 0.03) and watchful waiting >18 months prior to treatment (HR 0.3; CI 0.2-0.6; p = 0.001) were independently associated with OS. 15% of curatively treated patients (n = 60) were relapse-free with mFU of 87 months.

    Conclusions: OS after SRT was comparable to SM and longer than expected considering patients with adverse risk profiles were common. Fit patients with non-brain metastases treated after an initial period of watchful waiting had the best prognosis.

  • 12.
    Stenman, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Staehler, Michael
    Deparment of Urology, Ludwig-Maximilians University, Munich Germany.
    Szabados, Bernadett
    Deparment of Urology, Ludwig-Maximilians University, Munich Germany.
    Sandström, Per
    Department of Oncology-Pathology, Karolinska Institute, Sweden.
    Laurell, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Lindskog, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Harmenberg, Ulrika
    Department of Oncology-Pathology, Karolinska Institute, Sweden.
    Metastatic papillary renal cell carcinoma in the era of targeted therapy: a retrospective study from three European academic centres2019In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 58, no 3, p. 306-312Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Metastatic papillary renal cell carcinoma (mPRCC) is understudied. The disease is often aggressive and specific treatment options are lacking.

    PATIENTS AND METHODS: mPRCC patients (n = 86) referred to three academic centres in Sweden and Germany in the years 2005-2015 were retrospectively identified from medical records. Statistical analyses included Kaplan-Meier curves and calculation of Cox proportional hazards, generating hazard ratios with 95% confidence intervals. The aim of the study was to evaluate overall survival (OS) of mPRCC patients treated outside of clinical trials in the era of targeted agents (TA) and to identify clinically useful prognostic factors.

    RESULTS: Median OS of all mPRCC patients was 11.2 months. TA were used in 77% of the patients and associated with younger age and better Eastern Cooperative Oncology Group performance status (PS). Brain metastases were common (28%). Patients with synchronous or metachronous metastases had similar OS. Variables independently associated with risk of death included age ≥60 years, worse PS and ≥3 metastatic sites. The MSKCC criteria did not provide additional prognostic information. A subgroup analysis of TA-treated patients revealed an association of lymph node metastasis with risk of death in addition to the other prognostic factors.

    CONCLUSION: OS in mPRCC remained short in the era of targeted agents. Age, PS, and number of metastatic sites provided independent prognostic information.

  • 13. Sörenson, S.
    et al.
    Fohlin, H.
    Lindgren, A.
    Lindskog, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine.
    Bergman, B.
    Sederholm, C.
    Ek, L.
    Lamberg, Kristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Clinchy, B.
    Predictive role of plasma vascular endothelial growth factor for the effect of celecoxib in advanced non-small cell lung cancer treated with chemotherapy2013In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 49, no 1, p. 115-120Article in journal (Refereed)
    Abstract [en]

    Aim of the study:

    The primary purpose of this study is to investigate if pretreatment plasma levels of vascular endothelial growth factor (VEGF) are predictive of the effect of celecoxib on survival in advanced non-small cell lung cancer (NSCLC) treated with palliative chemotherapy. A secondary objective is to describe the course of plasma VEGF levels during and after treatment with cytotoxic chemotherapy combined with celecoxib or placebo.

    Methods:

    In a previously published double-blind multicenter phase III trial, 316 patients with NSCLC stage IIIB or IV and World Health Organisation (WHO) performance status 0-2 were randomised to receive celecoxib 400 mg b.i.d. or placebo in combination with two-drug platinum-based chemotherapy. Chemotherapy cycle length was three weeks and planned duration of chemotherapy was four cycles. Celecoxib was given for a maximum of one year but was stopped earlier in case of disease progression or prohibitive toxicity. In a subset of patients, plasma VEGF levels were examined at onset of treatment and at 6, 12 and 20 weeks.

    Results:

    VEGF levels at start of treatment were obtained in 107 patients at four study sites. The median value was 70 pg/ml. Mean values declined during the first 12 weeks and then increased at 20 weeks. A subpopulation treatment effect pattern plot (STEPP) analysis showed an inverse relationship between initial plasma VEGF and the impact of celecoxib on survival with zero effect at 200 pg/ml. The effect on survival by celecoxib in the whole subset of patients was positive (hazard ratio (HR) = 0.64 [confidence interval (CI) 0.43-0.95], p = 0.028).

    Conclusion:

    Low pretreatment plasma levels of VEGF appear to be predictive of a positive effect of celecoxib on survival.

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