Increased stomach cancer risk following radiotherapy for testicular cancer

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Abstract

Background:

Abdominal radiotherapy for testicular cancer (TC) increases risk for second stomach cancer, although data on the radiation dose–response relationship are sparse.

Methods:

In a cohort of 22 269 5-year TC survivors diagnosed during 1959–1987, doses to stomach subsites were estimated for 92 patients who developed stomach cancer and 180 matched controls. Chemotherapy details were recorded. Odds ratios (ORs) were estimated using logistic regression.

Results:

Cumulative incidence of second primary stomach cancer was 1.45% at 30 years after TC diagnosis. The TC survivors who received radiotherapy (87 (95%) cases, 151 (84%) controls) had a 5.9-fold (95% confidence interval (CI) 1.7–20.7) increased risk of stomach cancer. Risk increased with increasing stomach dose ( P-trend<0.001), with an OR of 20.5 (3.7–114.3) for ⩾50.0 Gy compared with <10 Gy. Radiation-related risks remained elevated ⩾20 years after exposure ( P<0.001). Risk after any chemotherapy was not elevated (OR=1.1; 95% CI 0.5–2.5; 14 cases and 23 controls).

Conclusions:

Radiotherapy for TC involving parts of the stomach increased gastric cancer risk for several decades, with the highest risks after stomach doses of ⩾30 Gy. Clinicians should be aware of these excesses when previously irradiated TC survivors present with gastrointestinal symptoms and when any radiotherapy is considered in newly diagnosed TC patients.

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Most cited references 43

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Estimation of failure probabilities in the presence of competing risks: new representations of old estimators.

T Gooley, W Leisenring, J. Crowley … (1999)

A topic that has received attention in both the statistical and medical literature is the estimation of the probability of failure for endpoints that are subject to competing risks. Despite this, it is not uncommon to see the complement of the Kaplan-Meier estimate used in this setting and interpreted as the probability of failure. If one desires an estimate that can be interpreted in this way, however, the cumulative incidence estimate is the appropriate tool to use in such situations. We believe the more commonly seen representations of the Kaplan-Meier estimate and the cumulative incidence estimate do not lend themselves to easy explanation and understanding of this interpretation. We present, therefore, a representation of each estimate in a manner not ordinarily seen, each representation utilizing the concept of censored observations being 'redistributed to the right.' We feel these allow a more intuitive understanding of each estimate and therefore an appreciation of why the Kaplan-Meier method is inappropriate for estimation purposes in the presence of competing risks, while the cumulative incidence estimate is appropriate.

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Second cancers among 40,576 testicular cancer patients: focus on long-term survivors.

Lois B. Travis, Sophie Fosså, Sara Schonfeld … (2005)

Although second primary cancers are a leading cause of death among men with testicular cancer, few studies have quantified risks among long-term survivors. Within 14 population-based tumor registries in Europe and North America (1943-2001), we identified 40,576 1-year survivors of testicular cancer and ascertained data on any new incident solid tumors among these patients. We used Poisson regression analysis to model relative risks (RRs) and excess absolute risks (EARs) of second solid cancers. All statistical tests were two-sided. A total of 2,285 second solid cancers were reported in the cohort. The relative risk and EAR decreased with increasing age at testicular cancer diagnosis (P < .001); the EAR increased with attained age (P < .001) but the excess RR decreased. Among 10-year survivors diagnosed with testicular cancer at age 35 years, the risk of developing a second solid tumor was increased (RR = 1.9, 95% confidence interval [CI] = 1.8 to 2.1). Risk remained statistically significantly elevated for 35 years (RR = 1.7, 95% CI = 1.5 to 2.0; P < .001). We observed statistically significantly elevated risks, for the first time, for cancers of the pleura (malignant mesothelioma; RR = 3.4, 95% CI = 1.7 to 5.9) and esophagus (RR = 1.7, 95% CI = 1.0 to 2.6). Cancers of the lung (RR = 1.5, 95% CI = 1.2 to 1.7), colon (RR = 2.0, 95% CI = 1.7 to 2.5), bladder (RR = 2.7, 95% CI = 2.2 to 3.1), pancreas (RR = 3.6, 95% CI = 2.8 to 4.6), and stomach (RR = 4.0, 95% CI = 3.2 to 4.8) accounted for almost 60% of the total excess. Overall patterns were similar for seminoma and nonseminoma patients, with lower risks observed for nonseminoma patients treated after 1975. Statistically significantly increased risks of solid cancers were observed among patients treated with radiotherapy alone (RR = 2.0, 95% CI = 1.9 to 2.2), chemotherapy alone (RR = 1.8, 95% CI = 1.3 to 2.5), and both (RR = 2.9, 95% CI = 1.9 to 4.2). For patients diagnosed with seminomas or nonseminomatous tumors at age 35 years, cumulative risks of solid cancer 40 years later (i.e., to age 75 years) were 36% and 31%, respectively, compared with 23% for the general population. Testicular cancer survivors are at statistically significantly increased risk of solid tumors for at least 35 years after treatment. Young patients may experience high levels of risk as they reach older ages. The statistically significantly increased risk of malignant mesothelioma in testicular cancer survivors has, to our knowledge, not been observed previously in a cohort of patients treated with radiotherapy.

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Epidemiology of stomach cancer.

Dietrich Rothenbacher, Volker Arndt, Hermann Brenner (2008)

Despite a major decline in incidence and mortality over several decades, stomach cancer is still the fourth most common cancer and the second most common cause of cancer death in the world. There is a 10-fold variation in incidence between populations at the highest and lowest risk. The incidence is particularly high in East Asia, Eastern Europe, and parts of Central and South America, and it is about twice as high among men than among women. Prognosis is generally rather poor, with 5-year relative survival below 30% in most countries. The best established risk factors for stomach cancer are Helicobacter pylori infection, the by far strongest established risk factor for distal stomach cancer, and male sex, a family history of stomach cancer, and smoking. While some factors related to diet and food preservation, such as high intake of salt-preserved foods and dietary nitrite or low intake of fruit and vegetables, are likely to increase the risk of stomach cancer, the quantitative impact of many dietary factors remains uncertain, partly due to limitations of exposure assessment and control for confounding factors. Future epidemiologic research should pay particular attention to differentiation of stomach cancer epidemiology by subsite, and to exploration of potential interactions between H. pylori infection, genetic, and environmental factors.

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Author and article information

Journal

Journal ID (nlm-ta): Br J Cancer

Journal ID (iso-abbrev): Br. J. Cancer

Title: British Journal of Cancer

Publisher: Nature Publishing Group

ISSN (Print): 0007-0920

ISSN (Electronic): 1532-1827

Publication date (Print): 06 January 2015

Publication date (Electronic): 04 November 2014

Volume: 112

Issue: 1

Pages: 44-51

Affiliations

[1 ]Department of Epidemiology and Biostatistics, The Netherlands Cancer Institute , Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands

[2 ]Department of Oncology, Oslo University Hospital and University of Oslo , Oslo, Norway

[3 ]Department of Radiation Physics, The University of Texas MD Anderson Cancer Center , Houston, TX, USA

[4 ]Cancer Registry of Norway , Oslo, Norway

[5 ]Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS , Bethesda, MD, USA

[6 ]Department of Radiation Oncology, The Netherlands Cancer Institute , Amsterdam, The Netherlands

[7 ]Department of Oncology, Copenhagen University Hospital , Copenhagen, Denmark

[8 ]Department of Veterans Affairs Medical Center , Oklahoma City, OK, USA

[9 ]Department of Medical Epidemiology and Biostatistics, Karolinska Institutet , Stockholm, Sweden

[10 ]Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet , Stockholm, Sweden

[11 ]Dalla Lana School of Public Health, University of Toronto , Toronto, Ontario, Canada

[12 ]Department of Oncology, Helsinki University Central Hospital , Helsinki, Finland

[13 ]Department of Epidemiology, University of Iowa , Iowa City, IA, USA

[14 ]Finnish Cancer Registry, Institute for Statistical and Epidemiological Cancer Research , Helsinki, Finland

[15 ]School of Health Sciences, University of Tampere , Tampere, Finland

[16 ]Cancer Prevention and Documentation, Danish Cancer Society , Copenhagen, Denmark

[17 ]Department of Radiation Oncology, University of Rochester Medical Center , Rochester, NY, USA

Author notes

[* ]E-mail: m.hauptmann@ 123456nki.nl

Article

Publisher Item ID: bjc2014552

DOI: 10.1038/bjc.2014.552

PMC ID: 4453604

PubMed ID: 25349972

SO-VID: 9fed666d-7ab9-4e4c-a789-e670c37c12d3

License:

From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/

History

Date received : 01 June 2014

Date revision received : 02 October 2014

Date accepted : 04 October 2014

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Increased stomach cancer risk following radiotherapy for testicular cancer

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Abstract

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Karger: Oncology

Most cited references 43

Estimation of failure probabilities in the presence of competing risks: new representations of old estimators.

Second cancers among 40,576 testicular cancer patients: focus on long-term survivors.

Epidemiology of stomach cancer.

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Cited by 14

Most referenced authors 547