Second neoplasms after megavoltage radiation for pediatric tumors

Abstract

BACKGROUNDBecause ionizing radiation is a known carcinogen, diligent long‐term follow‐up in children exposed to therapeutic radiation is required. The authors updated an earlier study on the nature and risk of second neoplasms (SN) in patients treated with megavoltage radiotherapy as children.METHODSThe authors followed 446 children who were treated for a primary malignancy with megavoltage radiotherapy between January 16, 1954 and December 31, 1980. These children survived a minimum of 5 years. The nature and incidence of SNs were evaluated in this population. Patients with bilateral retinoblastoma or neurofibromatosis were excluded from the study due to their large genetically based predisposition for developing an SN.RESULTSThe Kaplan–Meier actuarial survival rate was 80% (95% confidence interval [CI] 74–85%) at 30 years for all patients. Thirty‐seven (8.3%) patients developed SNs, most of which occurred within the original radiation treatment field, 3.8–31.8 years (median, 15.5 years) after radiotherapy. The cumulative risk of developing an SN was 13% (95% CI 9–19%) at 30 years and the standardized incidence ratio for the development of any SN was 5.2 (95% CI 3.4–7.6%). The most common SNs were breast carcinoma (n = 8), skin carcinoma (five basal cell carcinomas, two malignant melanomas, and one dermatosarcoma), and meningiomas (n = 6). All eight breast carcinomas occurred after the treatment of childhood Hodgkin disease. Of the 37 patients with SNs, 12 died of either the SN (n = 10) or of recurrent disease (n = 2). Risk factors associated with developing a SN included initial diagnosis of Hodgkin disease (P = 0.0003), female gender (P = 0.008), and an initial diagnosis of acute lymphoblastic leukemia (P = 0.02).CONCLUSIONSPatients in the radiation‐treated cohort experienced increased mortality, were at an increased risk of developing an SN, and should undergo increased medical surveillance as adults. The cumulative probability of developing an SN has increased substantially at 30 years, largely due to an increase in follow‐up time. In addition, the cumulative probability curve does not show evidence of plateau after increased duration of follow‐up. Finally, the emergence of secondary breast carcinoma in the current study was not noted in the previous analysis. Cancer 2003;10:2588–96. © 2003 American Cancer Society.DOI 10.1002/cncr.11356

Does electron and proton therapy reduce the risk of radiation induced cancer after spinal irradiation for childhood medulloblastoma? A comparative treatment planning study

“…Thus, an observation time longer than 50 years would be necessary for confirming the incidence of SLC in this population. In a later study on 446 patients that had undergone radiotherapy in childhood and survived for a minimum of 5 years, 26 developed second cancers whereas 5 would be expected [4]. The same authors estimate the cumulative risk for developing a second cancer to 13% after 30 years, and still the cumulative risk curve does not reach the plateau.…”

“…Several reports have been published concerning secondary cancer in long-term survivors of childhood cancer [4,5,43]. Radiation therapy is the most important risk factor for secondary cancer; the risk is further increased when chemotherapy is added [44].…”

“…Radiation-induced secondary cancer is a late sideeffect of great concern in paediatric cancer treatment [4,5]. Several conformal techniques for treating the cranial part of the target volume have been described [6,7].…”

Risk factors for subsequent endocrine-related cancer in childhood cancer survivors

“…This represents a standardized incidence ratio of 2.2-9.8 in comparison with the general population (Inskip & Curtis 2007, Olsen et al 2009, Friedman et al 2010, Reulen et al 2011. Latency periods for the development of secondary breast cancer following childhood cancer vary between 6.7 and 39 years (average 21.8 years) (Table 3) (Gold et al 2003, Taylor et al 2007, Constine et al 2008, Diallo et al 2009, Friedman et al 2010, O'Brien et al 2010, Lange et al 2014, Dorffel et al 2015, Henderson et al 2015. This is illustrated by Reulen and coworkers, who observed an increased risk for secondary breast cancer in female childhood cancer survivors during the first three decades following primary cancer diagnosis, which gradually declined to general population norms at an attained survivor's age of 50 years (Reulen et al 2008).…”

“…Follow-up durations since childhood cancer are generally too short to assess the risk for secondary malignant neoplasms in aging childhood cancer survivors. Average follow-up durations since childhood cancer vary between 6.3 and 27.3 years in studies assessing secondary breast cancer risk (Hancock et al 1993, Metayer et al 2000, Ng et al 2002, Bhatia et al 2003, Gold et al 2003, Guibout et al 2005, Inskip & Curtis 2007, Constine et al 2008, Friedman et al 2008, Marees et al 2008, Alm El-Din et al 2009, De Bruin et al 2009, Maule et al 2011, Reulen et al 2011, Cooke et al 2013, Danner-Koptik et al 2013, Little et al 2014, Dorffel et al 2015, Schaapveld et al 2015, and 5.1-27 years in studies investigating secondary thyroid carcinoma risk (Crom et al 1997, Bhatia et al 2002, Cohen et al 2007, Inskip & Curtis 2007, Constine et al 2008, Taylor et al 2009, van Beek et al 2009, Friedman et al 2010, Maule et al 2011, Vivanco et al 2012, Danner-Koptik et al 2013, Caglar et al 2014, Clement et al 2015, de Vathaire et al 2015, Dorffel et al 2015, Brignardello et al 2016. Specific subtypes of secondary malignant neoplasms and potential risk-modifying factors yet unknown may become apparent at an adv...…”