G M Dores1, R E Curtis2, F E van Leeuwen3, M Stovall4, P Hall5, C F Lynch6, S A Smith4, R E Weathers4, H H Storm7, D C Hodgson8, R A Kleinerman2, H Joensuu9, T B Johannesen10, M Andersson11, E J Holowaty12, M Kaijser13, E Pukkala14, L Vaalavirta9, S D Fossa15, F Langmark10, L B Travis16, J F Fraumeni2, B M Aleman17, L M Morton2, E S Gilbert2. 1. Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda; Department of Veterans Affairs Medical Center, Oklahoma City, USA. Electronic address: doresg@mail.nih.gov. 2. Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda. 3. Department of Epidemiology and Biostatistics, The Netherlands Cancer Institute, Amsterdam, The Netherlands. 4. Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston,USA. 5. Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden. 6. Department of Epidemiology, University of Iowa, Iowa City, USA. 7. Cancer Prevention and Documentation, Danish Cancer Society, Copenhagen, Denmark. 8. Department of Radiation Oncology, University of Toronto, Toronto,Canada. 9. Department of Oncology, Helsinki University Central Hospital, Helsinki, Finland. 10. Cancer Registry of Norway, Oslo, Norway. 11. Department of Oncology, Copenhagen University Hospital, Copenhagen, Denmark. 12. Dalla Lana School of Public Health, University of Toronto, Toronto,Canada. 13. Clinical Epidemiology Unit, Department of Medicine, Karolinska Institute, Stockholm, Sweden. 14. Finnish Cancer Registry, Institute for Statistical and Epidemiological Cancer Research, Helsinki and School of Health Sciences, University of Tampere, Tampere, Finland. 15. Department of Oncology, Oslo University Hospital and University of Oslo, Oslo, Norway. 16. Department of Radiation Oncology, University of Rochester Medical Center, Rochester,USA. 17. Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Abstract
BACKGROUND: Although elevated risks of pancreatic cancer have been observed in long-term survivors of Hodgkin lymphoma (HL), no prior study has assessed the risk of second pancreatic cancer in relation to radiation dose and specific chemotherapeutic agents. PATIENTS AND METHODS: We conducted an international case-control study within a cohort of 19 882 HL survivors diagnosed from 1953 to 2003 including 36 cases and 70 matched controls. RESULTS: Median ages at HL and pancreatic cancer diagnoses were 47 and 60.5 years, respectively; median time to pancreatic cancer was 19 years. Pancreatic cancer risk increased with increasing radiation dose to the pancreatic tumor location (Ptrend = 0.005) and increasing number of alkylating agent (AA)-containing cycles of chemotherapy (Ptrend = 0.008). The odds ratio (OR) for patients treated with both subdiaphragmatic radiation (≥10 Gy) and ≥6 AA-containing chemotherapy cycles (13 cases, 6 controls) compared with patients with neither treatment was 17.9 (95% confidence interval 3.5-158). The joint effect of these two treatments was significantly greater than additive (P = 0.041) and nonsignificantly greater than multiplicative (P = 0.29). Especially high risks were observed among patients receiving ≥8400 mg/m(2) of procarbazine with nitrogen mustard or ≥3900 mg/m(2) of cyclophosphamide. CONCLUSION: Our study demonstrates for the first time that both radiotherapy and chemotherapy substantially increase pancreatic cancer risks among HL survivors treated in the past. These findings extend the range of nonhematologic cancers associated with chemotherapy and add to the evidence that the combination of radiotherapy and chemotherapy can lead to especially large risks. Published by Oxford University Press on behalf of the European Society for Medical Oncology 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.
BACKGROUND: Although elevated risks of pancreatic cancer have been observed in long-term survivors of Hodgkin lymphoma (HL), no prior study has assessed the risk of second pancreatic cancer in relation to radiation dose and specific chemotherapeutic agents. PATIENTS AND METHODS: We conducted an international case-control study within a cohort of 19 882 HL survivors diagnosed from 1953 to 2003 including 36 cases and 70 matched controls. RESULTS: Median ages at HL and pancreatic cancer diagnoses were 47 and 60.5 years, respectively; median time to pancreatic cancer was 19 years. Pancreatic cancer risk increased with increasing radiation dose to the pancreatic tumor location (Ptrend = 0.005) and increasing number of alkylating agent (AA)-containing cycles of chemotherapy (Ptrend = 0.008). The odds ratio (OR) for patients treated with both subdiaphragmatic radiation (≥10 Gy) and ≥6 AA-containing chemotherapy cycles (13 cases, 6 controls) compared with patients with neither treatment was 17.9 (95% confidence interval 3.5-158). The joint effect of these two treatments was significantly greater than additive (P = 0.041) and nonsignificantly greater than multiplicative (P = 0.29). Especially high risks were observed among patients receiving ≥8400 mg/m(2) of procarbazine with nitrogen mustard or ≥3900 mg/m(2) of cyclophosphamide. CONCLUSION: Our study demonstrates for the first time that both radiotherapy and chemotherapy substantially increase pancreatic cancer risks among HL survivors treated in the past. These findings extend the range of nonhematologic cancers associated with chemotherapy and add to the evidence that the combination of radiotherapy and chemotherapy can lead to especially large risks. Published by Oxford University Press on behalf of the European Society for Medical Oncology 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.
Entities:
Keywords:
Hodgkin lymphoma; chemotherapy; pancreatic cancer; radiotherapy; second cancer
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