Article, 2023

Risk of Subsequent Neoplasms in Childhood Cancer Survivors After Radiation Therapy: A PENTEC Comprehensive Review

International Journal of Radiation Oncology • Biology • Physics, ISSN 1879-355X, 0360-3016, Volume 119, 2, Pages 640-654, 10.1016/j.ijrobp.2023.07.025

Contributors

Casey, Dana L 0000-0001-6851-7653 (Corresponding author) [1] Vogelius, Ivan Richter 0000-0002-8877-1218 [2] Brodin, Nils Patrik 0000-0003-1061-0841 [3] Roberts, Kenneth B [4] Avanzo, Michele 0000-0003-1711-4242 [5] Moni, Janaki [6] Owens, Constance A 0000-0001-7208-394X [7] Ronckers, Cécile M 0000-0003-3524-4657 [8] Constine, Louis Sandy 0000-0003-0742-1740 [9] Bentzen, Søren Møller 0000-0002-7444-7564 [10] [11] Olch, Arthur J [12] [13]

Affiliations

  1. [1] University of North Carolina at Chapel Hill
    2. [NORA names: United States; America, North; OECD];
  2. [2] Rigshospitalet
    3. [NORA names: Capital Region of Denmark; Hospital; Denmark; Europe, EU; Nordic; OECD];
  3. [3] Albert Einstein College of Medicine
    4. [NORA names: United States; America, North; OECD];
  4. [4] Yale University
    5. [NORA names: United States; America, North; OECD];
  5. [5] Division of Medical Physics, Centro di Riferimento Oncologico Aviano IRCCS, Aviano, Italy.
    6. [NORA names: Italy; Europe, EU; OECD];

Abstract

PURPOSE: A Pediatric Normal Tissue Effects in the Clinic (PENTEC) analysis of published investigations of central nervous system (CNS) subsequent neoplasms (SNs), subsequent sarcomas, and subsequent lung cancers in childhood cancer survivors who received radiation therapy (RT) was performed to estimate the effect of RT dose on the risk of SNs and the modification of this risk by host and treatment factors. METHODS AND MATERIALS: A systematic literature review was performed to identify data published from 1975 to 2022 on SNs after prior RT in childhood cancer survivors. After abstract review, usable quantitative and qualitative data were extracted from 83 studies for CNS SNs, 118 for subsequent sarcomas, and 10 for lung SNs with 4 additional studies (3 for CNS SNs and 1 for lung SNs) later added. The incidences of SNs, RT dose, age, sex, primary cancer diagnosis, chemotherapy exposure, and latent time from primary diagnosis to SNs were extracted to assess the factors influencing risk for SNs. The excess relative ratio (ERR) for developing SNs as a function of dose was analyzed using inverse-variance weighted linear regression, and the ERR/Gy was estimated. Excess absolute risks were also calculated. RESULTS: The ERR/Gy for subsequent meningiomas was estimated at 0.44 (95% CI, 0.19-0.68); for malignant CNS neoplasms, 0.15 (95% CI, 0.11-0.18); for sarcomas, 0.045 (95% CI, 0.023-0.067); and for lung cancer, 0.068 (95% CI, 0.03-0.11). Younger age at time of primary diagnosis was associated with higher risk of subsequent meningioma and sarcoma, whereas no significant effect was observed for age at exposure for risk of malignant CNS neoplasm, and insufficient data were available regarding age for lung cancer. Females had a higher risk of subsequent meningioma (odds ratio, 1.46; 95% CI, 1.22-1.76; P < .0001) relative to males, whereas no statistically significant sex difference was seen in risk of malignant CNS neoplasms, sarcoma SNs, or lung SNs. There was an association between chemotherapy receipt (specifically alkylating agents and anthracyclines) and subsequent sarcoma risk, whereas there was no clear association between specific chemotherapeutic agents and risk of CNS SNs and lung SNs. CONCLUSIONS: This PENTEC systematic review shows a significant radiation dose-response relationship for CNS SNs, sarcomas, and lung SNs. Given the linear dose response, improved conformality around the target volume that limits the high dose volume might be a promising strategy for reducing the risk of SNs after RT. Other host- and treatment-related factors such as age and chemotherapy play a significant contributory role in the development of SNs and should be considered when estimating the risk of SNs after RT among childhood cancer survivors.

Keywords

CNS neoplasms, ERR/Gy, PENTEC, Pediatric Normal Tissue Effects, RT dose, Sn, absolute risk, abstract review, age, agents, analysis, associated with higher risk, association, cancer, cancer diagnosis, cancer survivors, central nervous system, chemotherapeutic agents, chemotherapy, chemotherapy exposure, chemotherapy receipt, childhood, childhood cancer survivors, clinic, comprehensive review, conformation, contributory role, data, development, development of SN, diagnosis, differences, dose, dose response, dose volume, dose-response relationship, effect, effects of RT doses, excess absolute risk, exposure, factors, factors influencing risk, females, function, function of dose, high dose volume, high risk, host, improved conformity, incidence, incidence of SN, insufficient data, investigation of central nervous system, latent time, linear dose response, linear regression, literature review, lung, lung cancer, male, malignant CNS neoplasms, meningiomas, modification, neoplasms, nervous system, normal tissue effects, primary cancer diagnosis, primary diagnosis, qualitative data, radiation, radiation dose-response relationship, radiation therapy, ratio, receipt, regression, relationship, relative ratios, response, review, risk, risk of SN, role, sarcoma, sarcoma risk, sex, sex differences, significant sex differences, statistically, statistically significant sex differences, study, survivors, system, systematic literature review, systematic review, target, target volume, therapy, time, tissue effects, treatment, treatment factors, volume, younger age

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