Radiation induced secondary malignancies: a review article

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Abstract

Radiation-induced second malignancies (RISM) is one of the important late side effects of radiation therapy and has an impact on optimal treatment decision-making. Many factors contribute to the development of RISM such as age at radiation, dose and volume of irradiated area, type of irradiated organ and tissue, radiation technique and individual and family history of cancer. Exact mechanism of RISM is unknown. But nowadays, it is a growing concern in oncology because of the increased number of cancer survivors and efforts are being made to prevent or decrease the incidence of RISM. The primary search for articles was carried via Google Scholar and PubMed with keywords included ‘radiation induced malignancies, second malignancies, and chemotherapy induced malignancies’. Additional papers were found through references from relevant articles. In this review article, we have discussed about the pathogenesis, factors contributing to RISM, screening and prevention strategies of RISM.

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Most cited references 53

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Intensity-modulated radiation therapy, protons, and the risk of second cancers.

Eric Hall (2006)

Intensity-modulated radiation therapy (IMRT) allows dose to be concentrated in the tumor volume while sparing normal tissues. However, the downside to IMRT is the potential to increase the number of radiation-induced second cancers. The reasons for this potential are more monitor units and, therefore, a larger total-body dose because of leakage radiation and, because IMRT involves more fields, a bigger volume of normal tissue is exposed to lower radiation doses. Intensity-modulated radiation therapy may double the incidence of solid cancers in long-term survivors. This outcome may be acceptable in older patients if balanced by an improvement in local tumor control and reduced acute toxicity. On the other hand, the incidence of second cancers is much higher in children, so that doubling it may not be acceptable. IMRT represents a special case for children for three reasons. First, children are more sensitive to radiation-induced cancer than are adults. Second, radiation scattered from the treatment volume is more important in the small body of the child. Third, the question of genetic susceptibility arises because many childhood cancers involve a germline mutation. The levels of leakage radiation in current Linacs are not inevitable. Leakage can be reduced but at substantial cost. An alternative strategy is to replace X-rays with protons. However, this change is only an advantage if the proton machine employs a pencil scanning beam. Many proton facilities use passive modulation to produce a field of sufficient size, but the use of a scattering foil produces neutrons, which results in an effective dose to the patient higher than that characteristic of IMRT. The benefit of protons is only achieved if a scanning beam is used in which the doses are 10 times lower than with IMRT.

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Reduced treatment intensity in patients with early-stage Hodgkin's lymphoma.

Bernd Dörken, Andreas Engert, Richard Greil … (2010)

Whether it is possible to reduce the intensity of treatment in early (stage I or II) Hodgkin's lymphoma with a favorable prognosis remains unclear. We therefore conducted a multicenter, randomized trial comparing four treatment groups consisting of a combination chemotherapy regimen of two different intensities followed by involved-field radiation therapy at two different dose levels. We randomly assigned 1370 patients with newly diagnosed early-stage Hodgkin's lymphoma with a favorable prognosis to one of four treatment groups: four cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by 30 Gy of radiation therapy (group 1), four cycles of ABVD followed by 20 Gy of radiation therapy (group 2), two cycles of ABVD followed by 30 Gy of radiation therapy (group 3), or two cycles of ABVD followed by 20 Gy of radiation therapy (group 4). The primary end point was freedom from treatment failure; secondary end points included efficacy and toxicity of treatment. The two chemotherapy regimens did not differ significantly with respect to freedom from treatment failure (P=0.39) or overall survival (P=0.61). At 5 years, the rates of freedom from treatment failure were 93.0% (95% confidence interval [CI], 90.5 to 94.8) with the four-cycle ABVD regimen and 91.1% (95% CI, 88.3 to 93.2) with the two-cycle regimen. When the effects of 20-Gy and 30-Gy doses of radiation therapy were compared, there were also no significant differences in freedom from treatment failure (P=1.00) or overall survival (P=0.61). Adverse events and acute toxic effects of treatment were most common in the patients who received four cycles of ABVD and 30 Gy of radiation therapy (group 1). In patients with early-stage Hodgkin's lymphoma and a favorable prognosis, treatment with two cycles of ABVD followed by 20 Gy of involved-field radiation therapy is as effective as, and less toxic than, four cycles of ABVD followed by 30 Gy of involved-field radiation therapy. Long-term effects of these treatments have not yet been fully assessed. (Funded by the Deutsche Krebshilfe and the Swiss Federal Government; ClinicalTrials.gov number, NCT00265018.)

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Subsequent neoplasms in 5-year survivors of childhood cancer: the Childhood Cancer Survivor Study.

Wendy Leisenring, Sue Hammond, Michaela S. Donaldson … (2010)

The occurrence of subsequent neoplasms has direct impact on the quantity and quality of life in cancer survivors. We have expanded our analysis of these events in the Childhood Cancer Survivor Study (CCSS) to better understand the occurrence of these events as the survivor population ages. The incidence of and risk for subsequent neoplasms occurring 5 years or more after the childhood cancer diagnosis were determined among 14,359 5-year survivors in the CCSS who were treated from 1970 through 1986 and who were at a median age of 30 years (range = 5-56 years) for this analysis. At 30 years after childhood cancer diagnosis, we calculated cumulative incidence at 30 years of subsequent neoplasms and calculated standardized incidence ratios (SIRs), excess absolute risks (EARs) for invasive second malignant neoplasms, and relative risks for subsequent neoplasms by use of multivariable Poisson regression. Among 14,359 5-year survivors, 1402 subsequently developed 2703 neoplasms. Cumulative incidence at 30 years after the childhood cancer diagnosis was 20.5% (95% confidence interval [CI] = 19.1% to 21.8%) for all subsequent neoplasms, 7.9% (95% CI = 7.2% to 8.5%) for second malignant neoplasms (excluding nonmelanoma skin cancer), 9.1% (95% CI = 8.1% to 10.1%) for nonmelanoma skin cancer, and 3.1% (95% CI = 2.5% to 3.8%) for meningioma. Excess risk was evident for all primary diagnoses (EAR = 2.6 per 1000 person-years, 95% CI = 2.4 to 2.9 per 1000 person-years; SIR = 6.0, 95% CI = 5.5 to 6.4), with the highest being for Hodgkin lymphoma (SIR = 8.7, 95% CI = 7.7 to 9.8) and Ewing sarcoma (SIR = 8.5, 95% CI = 6.2 to 11.7). In the Poisson multivariable analysis, female sex, older age at diagnosis, earlier treatment era, diagnosis of Hodgkin lymphoma, and treatment with radiation therapy were associated with increased risk of subsequent neoplasm. As childhood cancer survivors progress through adulthood, risk of subsequent neoplasms increases. Patients surviving Hodgkin lymphoma are at greatest risk. There is no evidence of risk reduction with increasing duration of follow-up.

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Author and article information

Journal

Journal ID (nlm-ta): Radiat Oncol J

Journal ID (iso-abbrev): Radiat Oncol J

Journal ID (publisher-id): ROJ

Title: Radiation Oncology Journal

Publisher: The Korean Society for Radiation Oncology

ISSN (Print): 2234-1900

ISSN (Electronic): 2234-3164

Publication date (Print): June 2018

Publication date (Electronic): 29 June 2018

Volume: 36

Issue: 2

Pages: 85-94

Affiliations

Department of Radiotherapy and Oncology, PGIMER, Chandigarh, India

Author notes

Correspondence: Renu Madan, MD, Department of Radiotherapy and Oncology, PGIMER, Chandigarh-160012, India. Tel: +91- 9868597027, E-mail: renumadan12@ 123456gmail.com

Article

Publisher ID: roj-2018-00290

DOI: 10.3857/roj.2018.00290

PMC ID: 6074073

PubMed ID: 29983028

SO-VID: ca7c26bc-a0d4-46b4-be70-0e5ca97f5dd3

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

History

Date received : 17 June 2018

Date revision received : 27 June 2018

Date accepted : 27 June 2018

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Radiation induced secondary malignancies: a review article

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Karger: Oncology

Most cited references 53

Intensity-modulated radiation therapy, protons, and the risk of second cancers.

Reduced treatment intensity in patients with early-stage Hodgkin's lymphoma.

Subsequent neoplasms in 5-year survivors of childhood cancer: the Childhood Cancer Survivor Study.

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Cited by 95

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