Increased pancreatic cancer risk following radiotherapy for testicular cancer.
Pancreatic cancer risk is elevated among testicular cancer (TC) survivors. However, the roles of specific treatments are unclear.



Among 23 982 5-year TC survivors diagnosed during 1947-1991, doses from radiotherapy to the pancreas were estimated for 80 pancreatic cancer patients and 145 matched controls. Chemotherapy details were recorded. Logistic regression was used to estimate odds ratios (ORs).



Cumulative incidence of second primary pancreatic cancer was 1.1% at 30 years after TC diagnosis. Radiotherapy (72 (90%) cases and 115 (80%) controls) was associated with a 2.9-fold (95% confidence interval (CI) 1.0-7.8) increased risk. The OR increased linearly by 0.12 per Gy to the pancreas (P-trend<0.001), with an OR of 4.6 (95% CI 1.9-11.0) for ⩾25 Gy vs <25 Gy. Radiation-related risks remained elevated ⩾20 years after TC diagnosis (P=0.020). The risk increased with the number of cycles of chemotherapy with alkylating or platinum agents (P=0.057), although only one case was exposed to platinum.



A dose-response relationship exists between radiation to the pancreas and subsequent cancer risk, and persists for over 20 years. These excesses, although small, should be considered when radiotherapy with exposure to the pancreas is considered for newly diagnosed patients. Additional data are needed on the role of chemotherapy.
Department of Epidemiology and Biostatistics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
Michael
M
Hauptmann
Cancer Registry of Norway, Oslo, Norway.
Tom
T
Børge Johannesen
Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA.
Ethel S
ES
Gilbert
Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Marilyn
M
Stovall
Department of Epidemiology and Biostatistics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
Flora E
FE
van Leeuwen
Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA.
Preetha
P
Rajaraman
Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Susan A
SA
Smith
Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Rita E
RE
Weathers
Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Berthe M P
BM
Aleman
Department of Oncology, Copenhagen University Hospital, Copenhagen, Denmark.
Michael
M
Andersson
Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA.
Rochelle E
RE
Curtis
Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA.
Graça M
GM
Dores
Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA.
Joseph F
JF
Fraumeni
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.|Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
Per
P
Hall
Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.
Eric J
EJ
Holowaty
Comprehensive Cancer Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
Heikki
H
Joensuu
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Magnus
M
Kaijser
Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA.
Ruth A
RA
Kleinerman
Cancer Registry of Norway, Oslo, Norway.
Frøydis
F
Langmark
Department of Epidemiology, University of Iowa, Iowa City, IA, USA.
Charles F
CF
Lynch
Finnish Cancer Registry, Institute for Statistical and Epidemiological Cancer Research, Helsinki, Finland.|School of Health Sciences, University of Tampere, Tampere, Finland.
Eero
E
Pukkala
Danish Cancer Society, Copenhagen, Denmark.
Hans H
HH
Storm
Comprehensive Cancer Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
Leila
L
Vaalavirta
Department of Epidemiology and Biostatistics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
Alexandra W
AW
van den Belt-Dusebout
Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA.
Lindsay M
LM
Morton
Department of Oncology, Oslo University Hospital and University of Oslo, Oslo, Norway.
Sophie D
SD
Fossa
Melvin and Bren Simon Cancer Center, Indianapolis University School of Medicine, Indianapolis, IN, USA.
Lois B
LB
Travis
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D003131:Combined Modality Therapy; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009381:Neoplasms, Radiation-Induced / Q000453:epidemiology / Q000209:etiology; D016609:Neoplasms, Second Primary / Q000453:epidemiology* / Q000209:etiology; D009919:Orchiectomy; D058958:Organs at Risk; D010179:Pancreas / Q000528:radiation effects; D010190:Pancreatic Neoplasms / Q000453:epidemiology* / Q000209:etiology; D011879:Radiotherapy Dosage; D012306:Risk; D013736:Testicular Neoplasms / Q000188:drug therapy / Q000532:radiotherapy* / Q000601:surgery; D055815:Young Adult