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2.
  • Tandstad, T., et al. (author)
  • Treatment of stage I seminoma, with one course of adjuvant carboplatin or surveillance, risk-adapted recommendations implementing patient autonomy: a report from the Swedish and Norwegian Testicular Cancer Group (SWENOTECA)
  • 2016
  • In: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 27:7, s. 1299-1304
  • Journal article (peer-reviewed)abstract
    • A total of 1118 patients with clinical stage I seminoma one course of adjuvant carboplatin or managed by surveillance were included. Stromal invasion of rete testis and tumor size > 4 cm are confirmed as risk factors predicting relapse. Relapse rates following one course of adjuvant carboplatin is high and there is need to explore more effective adjuvant treatment options in patients with seminoma.The purpose of the protocol was to reduce the treatment burden in clinical stage I (CSI) seminoma by offering risk-adapted treatment. The protocol aimed to prospectively validate the proposed risk factors for relapse, stromal invasion of the rete testis and tumor diameter > 4 cm, and to evaluate the efficacy of one course of adjuvant carboplatin. From 2007 to 2010, 897 patients were included in a prospective, population-based, risk-adapted treatment protocol implementing one course of adjuvant carboplatin AUC7 (>n = 469) or surveillance (>n = 422). In addition, results from 221 patients receiving carboplatin between 2004 and 2007 are reported. At a median follow-up of 5.6 years, 69 relapses have occurred. Stromal invasion of the rete testis [hazard ratio (HR) 1.9, >P = 0.011] and tumor diameter > 4 cm (HR 2.7, >P < 0.001) were identified as risk factors predicting relapse. In patients without risk factors, the relapse rate (RR) was 4.0% for patients managed by surveillance and 2.2% in patients receiving adjuvant carboplatin. In patients with one or two risk factors, the RR was 15.5% in patients managed by surveillance and 9.3% in patients receiving adjuvant carboplatin. We found no increased RR in patients receiving carboplatin < 7 x AUC compared with that in patients receiving a parts per thousand yen7 x AUC. Stromal invasion in the rete testis and tumor diameter > 4 cm are risk factors for relapse in CSI seminoma. Patients without risk factors have a low RR and adjuvant therapy is not justified in these patients. The efficacy of adjuvant carboplatin is relatively low and there is need to explore more effective adjuvant treatment options in patients with high-risk seminoma. The data do not support the concept of a steep dose response for adjuvant carboplatin.
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3.
  • Beyer, J., et al. (author)
  • Maintaining success, reducing treatment burden, focusing on survivorship: highlights from the third European consensus conference on diagnosis and treatment of germ-cell cancer
  • 2013
  • In: Annals of Oncology. - : Elsevier BV. - 1569-8041 .- 0923-7534. ; 24:4, s. 878-888
  • Research review (peer-reviewed)abstract
    • In November 2011, the Third European Consensus Conference on Diagnosis and Treatment of Germ-Cell Cancer (GCC) was held in Berlin, Germany. This third conference followed similar meetings in 2003 (Essen, Germany) and 2006 (Amsterdam, The Netherlands) [Schmoll H-J, Souchon R, Krege S et al. European consensus on diagnosis and treatment of germ-cell cancer: a report of the European Germ-Cell Cancer Consensus Group (EGCCCG). Ann Oncol 2004; 15: 1377-1399; Krege S, Beyer J, Souchon R et al. European consensus conference on diagnosis and treatment of germ-cell cancer: a report of the second meeting of the European Germ-Cell Cancer Consensus group (EGCCCG): part I. Eur Urol 2008; 53: 478-496; Krege S, Beyer J, Souchon R et al. European consensus conference on diagnosis and treatment of germ-cell cancer: a report of the second meeting of the European Germ-Cell Cancer Consensus group (EGCCCG): part II. Eur Urol 2008; 53: 497-513]. A panel of 56 of 60 invited GCC experts from all across Europe discussed all aspects on diagnosis and treatment of GCC, with a particular focus on acute and late toxic effects as well as on survivorship issues. The panel consisted of oncologists, urologic surgeons, radiooncologists, pathologists and basic scientists, who are all actively involved in care of GCC patients. Panelists were chosen based on the publication activity in recent years. Before the meeting, panelists were asked to review the literature published since 2006 in 20 major areas concerning all aspects of diagnosis, treatment and follow-up of GCC patients, and to prepare an updated version of the previous recommendations to be discussed at the conference. In addition, similar to 50 E-vote questions were drafted and presented at the conference to address the most controversial areas for a poll of expert opinions. Here, we present the main recommendations and controversies of this meeting. The votes of the panelists are added as online supplements.
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4.
  • Björkholm, Magnus, et al. (author)
  • Central nervous system occurrence in elderly patients with aggressive lymphoma and a long-term follow-up
  • 2007
  • In: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 18:6, s. 1085-1089
  • Journal article (peer-reviewed)abstract
    • 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.
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5.
  • Jerkeman, Mats, et al. (author)
  • Prognostic implications of BCL6 rearrangement in uniformly treated patients with diffuse large B-cell lymphoma--a Nordic Lymphoma Group study.
  • 2002
  • In: International Journal of Oncology. - 1019-6439. ; 20:1, s. 161-165
  • Journal article (peer-reviewed)abstract
    • The purpose of this study was to investigate the prognostic implications of BCL6 rearrangement in a uniformly treated population of patients with diffuse large B-cell lymphoma (DLBCL) and to characterise the relationship between BCL6 rearrangement and prognostic factors. A total of 269 patients with DLBCL entered a randomised trial comparing the chemotherapy regimen CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) to the MACOP-B (methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, bleomycin) regimen. In 44 cases, frozen tissue was available for assessment of BCL6 status by Southern blot analysis. BCL6 was rearranged in six of 43 evaluable cases (14%), and was associated with elevated lactate dehydrogenase (LDH), and a higher patient age. No association between BCL6 status and expression of BCL2, Ki-67 or TP53 was found. Patients presenting with BCL6 rearrangement displayed a weak trend towards better overall and failure-free survival (67 and 67% at 5 years), compared to patients with germline BCL6 (63 and 52%), but the difference was not statistically significant. In accordance with previously published series, the presence of BCL6 rearrangement does not define a prognostically distinct subgroup of DLBCL. Assessment of BCL6 status may, however, be of clinical interest when related to other prognostic variables.
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6.
  • Krege, Susanne, et al. (author)
  • European consensus conference on diagnosis and treatment of germ cell cancer: A report of the second meeting of the European Germ Cell Cancer Consensus Group (EGCCCG): Part I
  • 2008
  • In: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 53:3, s. 478-496
  • Research review (peer-reviewed)abstract
    • Objectives: The first consensus report presented by the European Germ Cell Cancer Consensus Group (EGCCCG) in the year 2004 has found widespread approval by many colleagues throughout the world. In November 2006, the group met a second time under the auspices of the Department of Urology of the Amsterdam Medical Center, Amsterdam, The Netherlands. Methods: Medical oncologists, urological surgeons, radiation oncologists as well as pathologists from several European countries reviewed and discussed the data that had emerged since the 2002 conference, and incorporated the new data into updated and revised guidelines. As for the first meeting, the methodology of evidence-based medicine (EBM) was applied. The results of the discussion were compiled by the writing committee. All participants have agreed to this final update. Results: The first part of the consensus paper describes the clinical presentation of the primary tumor, its treatment, the importance and treatment of testicular intraepithelial neoplasia (TIN), histological classification, staging and prognostic factors, and treatment of stage I seminoma and non-seminoma. Conclusions: Whereas the vast majority of the recommendations made in 2004 remain valid 3 yr later, refinements in the treatment of early- and advanced-stage testicular cancer have emerged from clinical trials. Despite technical improvements, expert clinical skills will continue to be one of the major determinants for the prognosis of patients with germ cell cancer. In addition, the particular needs of testicular cancer survivors have been acknowledged. (C) 2007 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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7.
  • Krege, Susanne, et al. (author)
  • European consensus conference on diagnosis and treatment of germ cell cancer: A report of the second meeting of the European Germ Cell Cancer Consensus Group (EGCCCG): Part II
  • 2008
  • In: European Urology. - : Elsevier BV. - 1873-7560 .- 0302-2838. ; 53:3, s. 497-513
  • Research review (peer-reviewed)abstract
    • Objectives: The first consensus report that had been presented by the European Germ Cell Cancer Consensus Group (EGCCCG) in 2004 has found widespread approval by many colleagues throughout the world. In November 2006, the group met a second time under the auspices of the Department of Urology of the Amsterdam Medical Center, The Netherlands. Methods: Medical oncologists, urologic surgeons, radiation oncologists as well as pathologists from several European countries reviewed and discussed the data that had emerged since the 2002 conference and incorporated the new data into updated and revised guidelines. As for the first meeting the methodology of evidence-based medicine (EBM) was applied. The results of the discussion were compiled by the writing committee. All participants have agreed to this final update. Results: The second part of the consensus paper includes the treatment of metastasised disease, residual tumour resection, salvage therapy, follow-up, and late toxicities. Conclusions: Whereas the vast majority of the recommendations made in 2004 remain valid 3 yr later, refinements in the treatment of early-stage as well as of advanced-stage testicular cancer have emerged from clinical trials. Despite technical improvements, expert clinical skills will continue to be one of the major determinants for the prognosis of patients with germ cell cancer. in addition, the particular needs of testicular cancer survivors have been acknowledged. (C) 2007 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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8.
  • Lundin, J, et al. (author)
  • Phase 2 study of alemtuzumab (anti-CD52 monoclonal antibody) in patients with advanced mycosis fungoides/Sezary syndrome
  • 2003
  • In: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 101:11, s. 4267-4272
  • Journal article (peer-reviewed)abstract
    • This phase 2 study evaluated the safety and efficacy of alemtuzumab in 22 patients with advanced mycosis fungoides/Sezary syndrome (MF/SS). Most patients had stage III or IV disease, reduced performance status, and severe itching. The overall response (OR) rate was 55%, with 32% of patients in complete remission (CR) and M in, partial remission (PR). Sezary cells were cleared from the blood in 6 of 7 (86%) patients, and CR in lymph nodes was observed in 6 of 11 (55%) patients. The effect was better on erythro-derma (OR, 69%) than on plaque or skin tumors (OR, 40%) and in patients who had received 1 to 2 previous regimens (OR, 80%) thin in those who had received 3 or more prior regimens (OR, 33%). Itching, self-assessed on a 0 to 10 visual analog scale, was reduced from a median of 8 before treatment to 2 at end. of therapy. Median time to treatment failure was 12 months (range, 5-32+ months). Cytomegalovirus (CMV), reactivation (causing fever without pneumonitis and responding to ganciclovir) occurred in 4 (18%) patients. Six additional patients had suspect or manifest infection (fever of unknown origin, 3, generalized herpes simplex, 1, fatal aspergillosis, 1). One patient had fatal Mycobacterium pneumonia at 10+ months. All serious infectious adverse events (except CMV) occurred in patients who had received 3 or more prior regimens. Progression of squamous cell skin carcinoma was noted in 1 patient. Alemtuzumab shows promising clinical activity and an acceptable safety profile in patients with advanced MF/SS, particularly in patients with erythroderma and severe itching and those who were not heavily pretreated. (C) 2003 by The American Society of Hematology.
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9.
  • Nord, Carina, et al. (author)
  • Sick leave and disability pension among Swedish testicular cancer survivors according to clinical stage and treatment
  • 2015
  • In: Acta Oncologica. - 1651-226X .- 0284-186X. ; 54:10, s. 1770-1780
  • Journal article (peer-reviewed)abstract
    • Purpose. To investigate if testicular cancer survivors (TCSs) have a higher incidence of work loss compared with the population, accounting for stage, treatment and relapse.Material and methods. A cohort of 2146 Swedish TCSs diagnosed 1995-2007 (seminoma n = 926, non-seminoma n = 1220) was identified in the SWENOTECA (Swedish-Norwegian Testicular Cancer Group) register, and matched 1:4 to population comparators. Prospectively recorded work loss data (both before and after diagnosis) were obtained from national registers through September 2013. Adjusted relative risks (RR) and 95% confidence intervals (CI) of sick leave and/or disability pension were calculated annually and overall with Poisson- and Cox regression, censoring at relapse. The mean number of annual work days lost was also estimated.Results. TCSs were at a modestly increased annual risk of work loss up to the third year of follow-up (RR3rd year 1.25, 95% CI 1.08, 1.43), attributed to a more pronounced risk among extensively treated patients (4 chemotherapy courses: RR3rd year 1.60, 95% CI 1.19, 2.15; > 4 courses: RR3rd year 3.70, 95% CI 2.25, 6.11). Patients on surveillance or limited treatment (radiotherapy, 1-3 chemotherapy courses) did not have an increased risk of work loss beyond the first year. TCSs receiving > 4 chemotherapy courses had higher mean number of annual days of work loss up to the 10th year post-diagnosis, and a five-fold risk of disability pension (RR 5.16, 95% CI 2.00, 10.3).Conclusion. Extensively treated TCSs, but not those on surveillance or limited treatment, are at increased risk of work loss long-term, not explained by relapse. These patients may benefit from early rehabilitation initiatives.
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10.
  • Osby, E, et al. (author)
  • CHOP is superior to CNOP in elderly patients with aggressive lymphoma while outcome is unaffected by filgrastim treatment: results of a Nordic Lymphoma Group randomized trial
  • 2003
  • In: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 101:10, s. 3840-3848
  • Journal article (peer-reviewed)abstract
    • This study was designed to test the hypothesis that administration of granulocyte colony-stimulating factor (G-CSF; filgrastim) during induction chemotherapy with CHOP (cyclophosphamide, vincristine, doxorubicin, prednisone) or CNOP (doxorubicin replaced with mitoxantrone) in elderly patients with aggressive non-Hodgkin lymphoma (NHL) improves time to treatment failure (TTF), complete remission (CR) rate, and overall survival (OS). Furthermore, the efficacy of CHOP versus CNOP chemotherapy was compared. A total of 455 previously untreated patients older than 60 years with stages 11 to IV aggressive NHL were included-in the analysis. Patients (median age, 71 years; range, 60-86 years) were randomized to receive CHOP (doxorubicin 50 mg/m(2)) or CNOP (mitoxantrone 10 mg/m(2)) with or without G-CSIF (5 mug/kg from day 2 until day 10-14 of each cycle every 3 weeks; 8 cycles). Forty-seven patients previously hospitalized for class I to 11 congestive heart failure were randomized to receive CNOP with or without G-CSF (not included in the CHOP versus CNOP analysis). The CR rates in the CHOP/CNOP plus G-CSF and CHOP/CNOP groups were the same, 52%, and in the CHOP with or without G-CSF and CNOP with or without G-CSF groups, 60% and 43% (P < .001), respectively. No benefit of G-CSF in terms of TTF and OS could be shown (P = .96 and P = .22, respectively), whereas CHOP was superior to CNOP (TTF/OS P < .001). The incidences of severe granulocytopenia (World Health Organization grade IV) and granulocytopenic infections were higher in patients not receiving G-CSF The cumulative proportion of patients receiving 90% or more of allocated chemotherapy was higher (P < .05) in patients receiving G-CSF. Concomitant G-CSF treatment did not improve CR rate, TTF, or OS. Patients receiving CHOP fared better than those given CNOP chemotherapy. The addition of G-CSF reduces the incidence of severe granulocytopenia and infections in elderly patients with aggressive NHL receiving CHOP or CNOP chemotherapy. (C) 2003 by The American Society of Hematology.
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11.
  • Rutqvist, L E, et al. (author)
  • A systematic overview of radiation therapy effects in breast cancer
  • 2003
  • In: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 42:5-6, s. 532-545
  • Journal article (peer-reviewed)abstract
    • A systematic review of radiation therapy trials in several turnout types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for evaluation of the scientific literature are described separately (Acta Oncol 2003; 42: 357-365). This synthesis of the literature on radiation therapy for breast cancer is based on data from 29 randomized trials, 6 meta-analyses and 5 retrospective studies. In total, 40 scientific articles are included, involving 41204 patients. The results were compared with those of a similar overview from 1996 including 285982 patients. The conclusions reached can be summarized as follows: There is strong evidence for a substantial reduction in locoregional recurrence rate following postmastectomy radiation therapy to the chest wall and the regional nodal areas. There is strong evidence that postmastectomy radiation therapy increases the disease-free survival rate. There are conflicting data regarding the impact of postmastectomy radiotherapy upon overall survival. There is strong evidence that breast cancer specific survival is improved by postmastectomy radiotherapy. There is strong evidence for a decrease in non-breast cancer specific survival after postmastectomy radiotherapy. There is some evidence that overall survival is increased by optimal postmastectomy radiation therapy. There is strong evidence that postmastectomy radiotherapy in addition to surgery and systemic therapy in mainly node-positive patients decreases local recurrence rate and improves survival. There is moderate evidence that the decrease in non-breast cancer specific survival is attributed to cardiovascular disease in irradiated patients. There are conflicting data whether breast conservation surgery plus radiotherapy is comparable to modified radical mastectomy alone in terms of local recurrence rate. There is strong evidence that breast conservation surgery plus radiotherapy is comparable to modified radical mastectomy alone in terms of disease-free survival and overall survival. There is strong evidence that postoperative radiotherapy to the breast following breast conservation surgery results in a statistically and clinically significant reduction of ipsilateral breast recurrences followed by diminished need for salvage mastectomies. There is strong evidence that the omission of postoperative radiotherapy to the breast following breast conservation surgery has no impact on overall survival. In one meta-analysis including three randomized studies a survival advantage is demonstrated by Bayesian statistics. There is strong evidence that the addition of a radiation boost after conventional radiotherapy to the turnout bed after breast conservation surgery significantly decreases the risk of ipsilateral breast recurrences but has no impact on overall survival after short follow-up. There is strong evidence for the use of postoperative radiotherapy to the breast following breast conservation surgery for DCIS (ductal breast cancer in situ). Radiotherapy leads to a clinically and statistically significant reduction of both non-invasive and invasive ipsilateral breast recurrences. There is insufficient evidence to define the optimal integration of systemic adjuvant therapy and postoperative radiotherapy. There are limited data on radiotherapy-related morbidity in breast cancer. No conclusions can be drawn.
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12.
  • Widmark, A, et al. (author)
  • A systematic overview of radiation therapy effects in urinary bladder cancer
  • 2003
  • In: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 42:5-6, s. 567-581
  • Journal article (peer-reviewed)abstract
    • A systematic review of radiation therapy trials in several turnout types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for evaluation of the scientific literature are described separately (Acta Oncol 2003; 42: 357-365). This synthesis of the literature on radiation therapy for urinary bladder cancer is based on data from 3 meta-analyses and 33 randomized trials. The studies include 4333 patients. The results were compared with those of a similar overview from 1996 including 15042 patients. The conclusions reached can be summarized as these points: There is moderate evidence for an overall survival benefit with preoperative radiotherapy followed by cystectomy compared to curative radiotherapy based on early studies (1964-1986). Since that time surgical as well as radiation techniques have developed considerably. Therefore. the conclusion may not be relevant to modern treatment of invasive urinary bladder carcinoma. There is only one small study reporting on curative radiotherapy where increased dose per fraction is compared with conventionally fractionated radiotherapy to the same total dose. Thus, no conclusions can be drawn concerning optimal fraction dose. A meta-analysis based on two studies on hyperfractionated radiotherapy gives moderate evidence of a survival benefit at 5 and 10 years and an increased local control rate compared with conventional fractionation. The documentation of local control and overall survival rate after split-course radiation treatment compared to continuous therapy is conflicting. No firm conclusions can be drawn. Four small and early studies have compared radiation treatment using neutrons with photon treatment. The reports favour therapy with photons with respect to overall treatment results. There is moderate evidence for this conclusion. There is fairly strong evidence in early studies that radiation treatment in combination with hyperbaric oxygen does not confer a treatment benefit compared to radiation in normal atmosphere. There is no indication of a treatment benefit with the addition of either hyperthermia or misonidazole. A large number of phase II studies, suggesting an increased possibility for bladder preservation with concomitant chemoradiotherapy compared to radiotherapy alone, have been reviewed in a previous SBU report on chemotherapy. Only one small randomized study has been reported where concomitant chemoradiotherapy with cisplatin is compared to radiation alone. No conclusion on the therapeutic benefit of combined treatment can be drawn. Large randomized studies are needed. There is some evidence that preoperative radiotherapy followed by cystectomy does not confer any significant survival benefit compared to cystectomy alone. There is moderate evidence that palliative radiotherapy of invasive bladder carcinoma can rapidly induce tumour-related symptom relief. There is moderate evidence that palliative hypofractionated radiotherapy, 3 fractions during one week, gives the same relief of symptoms as 10 fractions during 2 weeks.
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