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  • Chen, Lingjing, et al. (författare)
  • Short- and long-term risks of cardiovascular disease following radiotherapy in rectal cancer in four randomized controlled trials and a population-based register
  • 2018
  • Ingår i: Radiotherapy and Oncology. - : ELSEVIER IRELAND LTD. - 0167-8140 .- 1879-0887. ; 126:3, s. 424-430
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim: A population-based cohort and four randomized trials enriched with long-term register data were used to clarify if radiotherapy in combination with rectal cancer surgery is associated with increased risks of cardiovascular disease (CVD). Methods: We identified 14,901 rectal cancer patients diagnosed 1995-2009 in Swedish nationwide registers, of whom 9227 were treated with preoperative radiotherapy. Also, we investigated 2675 patients with rectal cancer previously randomized to preoperative radiotherapy or not followed by surgery in trials conducted 1980-1999. Risks of CVD overall and subtypes were estimated based on prospectively recorded hospital visits during relapse-free follow-up using multivariable Cox regression. Maximum follow-up was 18 and 33 years in the register and trials, respectively. Results: We found no association between preoperative radiotherapy and overall CVD risk in the register (Incidence Rate Ratio, IRR = 0.99, 95% confidence interval (CI) 0.92-1.06) or in the pooled trials (IRR = 1.07, 95% CI 0.93-1.24). We noted an increased risk of venous thromboembolism among irradiated patients in both cohorts (lRR(register) = 1.41, 95% CI 1.15-2.72; IRRtrials = 1.41, 95% CI 0.97-2.04), that remained during the first 6 months following surgery among patients treated 2006-2009, after the introduction of antithrombotic treatment (IRR6 (months) = 2.30, 95% CI 1.01-5.21). However, the absolute rate difference of venous thromboembolism attributed to RT was low (10 cases per 1000 patients and year). Discussion: Preoperative radiotherapy did not affect rectal cancer patients' risk of CVD overall. Although an excess risk of short-term venous thromboembolism was noted, the small increase in absolute numbers does not call for general changes in routine prophylactic treatment, but might do so for patients already at high risk of venous thromboembolism. (C) 2017 Elsevier B.V. All rights reserved.
  • Glimelius, B., et al. (författare)
  • Number of patients potentially eligible for proton therapy
  • 2005
  • Ingår i: Acta Oncol. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 44:8, s. 836-49
  • Tidskriftsartikel (refereegranskat)abstract
    • A group of Swedish radiation oncologists and hospital physicists have estimated the number of patients in Sweden suitable for proton beam therapy in a facility where one of the principal aims is to facilitate randomized and other studies in which the advantage of protons can be shown and the magnitude of the differences compared with optimally administered conventional radiation treatment, also including intensity-modulated radiation therapy (IMRT) and brachytherapy, can be shown. The estimations have been based on current statistics of tumour incidence in Sweden, number of patients potentially eligible for radiation treatment, scientific support from clinical trials and model dose planning studies and knowledge of the dose-response relations of different tumours together with information on normal tissue complication rates. In Sweden, it is assessed that between 2200 and 2500 patients annually are eligible for proton beam therapy, and that for these patients the potential therapeutic benefit is so great as to justify the additional expense of proton therapy. This constitutes between 14-15% of all irradiated patients annually.
  • Glimelius, Ingrid, 1975-, et al. (författare)
  • Bulky disease is the most important prognostic factor in Hodgkin lymphoma stage IIB
  • 2003
  • Ingår i: European Journal of Haematology. - : Wiley-Blackwell. - 0902-4441 .- 1600-0609. ; 71:5, s. 327-33
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study was to evaluate treatment results for Hodgkin lymphoma (HL) patients younger than 60 yr in stage IIB, treated according to the Swedish National Care Programme. The intention was also to identify specific subgroups depending on the number of negative prognostic factors the patients have, in order to optimise and differentiate future treatment. In total, 99 patients with HL stage IIB, diagnosed between 1985 and 1994, have been analysed. There were 47 men and 52 women and the median age was 33 yr (range 17-59). Eighty-six patients presented with supradiaphragmatic disease and 13 with infradiaphragmatic. The HL specific and overall 10-yr survival was 73 and 65%, respectively. The HL-specific survival for patients in pathological stage IIB tended to be better, although not statistically significant than for clinical stage IIB, despite less chemotherapy (P = 0.1). The patients in stage IIB who were selected for laparotomy were, however, younger and with fewer negative prognostic factors. The only significant negative prognostic factor was bulky disease (P = 0.001). The following factors also tended to have a negative influence on the prognosis although not statistically significant: the International Prognostic Score, the number of involved lymph node stations, extranodal involvement and leucocyte count > 15 x 10(9)/L. In conclusion, we suggest that bulky disease should be taken into account when treating patients with stage IIB HL.
  • Hollander, Peter, et al. (författare)
  • Autoimmune and Atopic Disorders and Risk of Classical Hodgkin Lymphoma
  • 2015
  • Ingår i: American Journal of Epidemiology. - 0002-9262 .- 1476-6256. ; 182:7, s. 624-632
  • Tidskriftsartikel (refereegranskat)abstract
    • Results from previous investigations have shown associations between the risk of Hodgkin lymphoma (HL) and a history of autoimmune and atopic diseases, but it remains unknown whether these associations apply to all types of HL or only to specific subtypes. We investigated immune diseases and the risk of classical HL in a population-based case-control study that included 585 patients and 3,187 controls recruited from October 1999 through August 2002. We collected information on immune diseases through telephone interviews and performed serological analyses of specific immunoglobulin E reactivity. Tumor Epstein-Barr virus (EBV) status was determined for 498 patients. Odds ratios with 95% confidence intervals were calculated using logistic regression analysis. Rheumatoid arthritis was associated with a higher risk of HL (odds ratio (OR) = 2.63; 95% confidence interval (CI): 1.47, 4.70), especially EBV-positive HL (OR = 3.18; 95% CI: 1.23, 8.17), and with mixed-cellularity HL (OR = 4.25; 95% CI: 1.66, 10.90). HL risk was higher when we used proxies of severe rheumatoid arthritis, such as ever having received daily rheumatoid arthritis medication (OR = 3.98; 95% CI: 2.08, 7.62), rheumatoid arthritis duration of 6-20 years (OR = 3.80; 95% CI: 1.72, 8.41), or ever having been hospitalized for rheumatoid arthritis (OR = 7.36; 95% CI: 2.95, 18.38). Atopic diseases were not associated with the risk of HL. EBV replication induced by chronic inflammation in patients with autoimmune diseases might explain the higher risk of EBV-positive HL.
  • Lagerlöf, Ingemar, et al. (författare)
  • No excess long-term mortality in stage I-IIA Hodgkin lymphoma patients treated with ABVD and limited field radiotherapy
  • 2020
  • Ingår i: British Journal of Haematology. - : Federation of European Neuroscience Societies and Blackwell Publishing Ltd. - 0007-1048 .- 1365-2141. ; 188:5, s. 685-691
  • Tidskriftsartikel (refereegranskat)abstract
    • When treating limited stage classical Hodgkin lymphoma (cHL), balancing treatment efficacy and toxicity is important. Toxicities after extended-field radiotherapy are well documented. Investigators have aimed at reducing toxicity without compromising efficacy, mainly by using combined modality treatment (CMT), i.e. chemotherapy and limited-field radiotherapy. In some clinical trials, radiotherapy has been omitted. We evaluated 364 patients with stage I-IIA cHL treated between 1999 and 2005. Patients were treated with two or four cycles of doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) according to presence of risk factors, followed by 30 Gy limited-field (reduced compared to involved-field) radiotherapy. After a median follow-up of 16 years for survival, freedom from progression at five and ten years was 93% and overall survival at 5 and 10 years was 98% and 96%, respectively. Only two relapses, out of 27, occurred after more than 5 years. There was no excess mortality compared to the general population. Of the analysed subgroups, only patients with progression within five years showed significant excess mortality. The absence of excess mortality questions the concept of omitting radiotherapy after short-term chemotherapy, a strategy that has been associated with an elevated risk of relapse but not yet with a proven reduced long-term excess mortality.
  • Molin, Daniel, et al. (författare)
  • Mast cell infiltration correlates with poor prognosis in Hodgkin's lymphoma
  • 2002
  • Ingår i: British Journal of Haematology. - 0007-1048 .- 1365-2141. ; 119:1, s. 122-124
  • Tidskriftsartikel (refereegranskat)abstract
    • Hodgkin's lymphoma (HL) is characterized by a few Hodgkin, Reed-Sternberg cells (HRS) surrounded by benign cells. We recently reported that mast cells were the predominant CD30L-positive cells in HL tumours, and that they activate HRS in vitro through CD30L-CD30 interaction. Here, we investigated the clinical importance of mast cell infiltration in the tumours of 123 patients. Tumour specimens were stained with a mast-cell-specific antibody that detects tryptase. Mast cells were detected in virtually every case and increasing numbers of mast cells correlated to nodular sclerosis histology (P = 0.008). Patients with higher mast cell infiltration had a worse relapse-free survival (P = 0.01).
  • Travis, Lois B, et al. (författare)
  • Breast cancer following radiotherapy and chemotherapy among young women with Hodgkin disease
  • 2003
  • Ingår i: Journal of the American Medical Association (JAMA). - 0098-7484 .- 1538-3598. ; 290:4, s. 465-475
  • Tidskriftsartikel (refereegranskat)abstract
    • CONTEXT: Second cancer is the leading cause of death in long-term survivors of Hodgkin disease (HD), with exceptionally high risks of breast cancer among women treated at a young age. Quantitative associations between radiotherapy dose delivered to the breast and administered chemotherapy have not been reported to date in large series, nor has the influence of ovarian exposures on subsequent risk.OBJECTIVE: To quantify the long-term risk of breast cancer associated with use of radiotherapy and chemotherapy to treat young women with HD.DESIGN, SETTING, AND SUBJECTS: Matched case-control study of breast cancer within a cohort of 3817 female 1-year survivors of HD diagnosed at age 30 years or younger, between January 1, 1965, and December 31, 1994, and within 6 population-based cancer registries. The study was conducted March 1, 1996, through September 30, 1998.MAIN OUTCOME MEASURES: Relative risk (RR) of breast cancer associated with radiation dose delivered to site of breast cancer or to ovaries and with cumulative dose of alkylating agents.RESULTS: Breast cancer occurred in 105 patients with HD who were matched to 266 patients with HD but without breast cancer. A radiation dose of 4 Gy or more delivered to the breast was associated with a 3.2-fold (95% confidence interval [CI], 1.4-8.2) increased risk, compared with the risk in patients who received lower doses and no alkylating agents. Risk increased to 8-fold (95% CI, 2.6-26.4) with a dose of more than 40 Gy (P<.001 for trend). Radiation risk did not vary appreciably by age at exposure or reproductive history. Increased risks persisted for 25 or more years following radiotherapy (RR, 2.3; 95% CI, 0.5-16.5; P =.03 for trend with dose). Treatment with alkylating agents alone resulted in a reduced risk (RR, 0.6; 95% CI, 0.2-2.0) of breast cancer, and combined alkylating agents and radiotherapy in a 1.4-fold (95% CI, 0.6-3.5) increased risk. Risk of breast cancer decreased with increasing number of alkylating agent cycles (P =.003 for trend). Risk also was low (RR, 0.4; 95% CI, 0.1-1.1) among women who received 5 Gy or more delivered to ovaries compared with those who received lower doses.CONCLUSIONS: Hormonal stimulation appears important for the development of radiation-induced breast cancer, as evidenced by the reduced risk associated with ovarian damage from alkylating agents or radiation. The high radiation-related risk, which did not diminish at the highest doses or the longest follow-up, however, suggests the need for lifetime surveillance and programs of patient and public awareness.
  • Travis, Lois B, et al. (författare)
  • Lung cancer following chemotherapy and radiotherapy for Hodgkin's disease
  • 2002
  • Ingår i: Journal of the National Cancer Institute. - 0027-8874 .- 1460-2105. ; 94:3, s. 182-192
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Lung cancer is a frequent cause of death in patients cured of Hodgkin's disease, but the contributions of chemotherapy, radiotherapy, and smoking are not well described. We quantified the risk of treatment-associated lung cancer, taking into account tobacco use.METHODS: Within a population-based cohort of 19 046 Hodgkin's disease patients (diagnosed from 1965 through 1994), a case-control study of lung cancer was conducted. The cumulative amount of cytotoxic drugs, the radiation dose to the specific location in the lung where cancer developed, and tobacco use were compared for 222 patients who developed lung cancer and for 444 matched control patients. All statistical tests were two-sided.RESULTS: Treatment with alkylating agents without radiotherapy was associated with increased lung cancer risk (relative risk [RR] = 4.2; 95% confidence interval [CI] = 2.1 to 8.8), as was radiation dose of 5 Gy or more without alkylating agents (RR = 5.9; 95% CI = 2.7 to 13.5). Risk increased with both increasing number of cycles of alkylating agents and increasing radiation dose (P for trend <.001). Among patients treated with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP), risk increased with cumulative amounts of mechlorethamine and procarbazine (P<.001) when evaluated separately. Statistically significantly elevated risks of lung cancer were apparent within 1-4 years after treatment with alkylating agents, whereas excess risk after radiotherapy began 5 years after treatment and persisted for more than 20 years. Risk after treatment with alkylating agents and radiotherapy together was as expected if individual excess risks were summed. Tobacco use increased lung cancer risk more than 20-fold; risks from smoking appeared to multiply risks from treatment.CONCLUSIONS: Past treatments with alkylating agents and radiation therapy for Hodgkin's disease were associated with an increased risk of lung cancer in a dose-dependent and additive fashion. The precise risk estimates, however, should be interpreted cautiously, given the possible residual and enhancing effects of tobacco.
  • Ask, Anders, et al. (författare)
  • The potential of proton beam radiation therapy in gastrointestinal cancer
  • 2005
  • Ingår i: Acta Oncologica. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 44:8, s. 896-903
  • Tidskriftsartikel (refereegranskat)abstract
    • A group of Swedish oncologists and hospital physicists have estimated the number of patients in Sweden suitable for proton beam therapy. The estimations have been based on current statistics of tumour incidence, number of patients potentially eligible for radiation treatment, scientific support from clinical trials and model dose planning studies and knowledge of the dose-response relations of different tumours and normal tissues. In gastrointestinal cancers, it is assessed that at least 345 patients, mainly non-resectable rectal cancers, oesophageal and liver cancers, are eligible. Great uncertainties do however exist both in the number of patients with gastrointestinal cancers suitable for radiation therapy, and in the proportion of those where proton beams may give sufficiently better results.
  • Glimelius, B., et al. (författare)
  • 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 cancer
  • 2008
  • Ingår i: Annals of Oncology. - : Oxford University Press. - 1569-8041 .- 0923-7534. ; 19:5, s. 909-914
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.
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