Very long-term outcomes of pediatric patients treated for optic pathway gliomas: A longitudinal cohort study.

BACKGROUND: Optic pathway gliomas (OPGs) represent 5% of childhood brain tumors. Successive relapses lead to multiple treatments exposing to late complications. METHODS: We included patients treated at Gustave Roussy (GR) between January 1980 and December 2015 for OPG, before 18 years old and alive at 5 years from diagnosis. Mortality and physical health conditions data were extracted from medical data files and updated, thanks to the GR long-term follow-up program and French national mortality registry for patients included in the French Childhood Cancer Survivor Study. RESULTS: We included 182 5-year OPG-childhood survivors in the analysis (sex ratio M/F 0.8, 35% with neurofibromatosis type 1 [NF1]). With a median follow-up of 17.2 years (range = 5-41), we registered 82 relapses, 9 second malignancies, and 15 deaths as first events after 5 years, resulting in 20-year conditional overall survival (C-OS) and late events-free survival of 79.9% (95% confidence interval [CI] = 71-86) and 43.5% (95% CI = 36-51), respectively. Radiotherapy exposure in NF1 patients (hazard ratio [HR] = 6, 95% CI = 1.7-21.2) and hypothalamic involvement (HR = 3.2, 95% CI = 1.4-7.3) were significantly associated with C-OS in multivariable analyses. Ninety-five percent of 5-year OPG survivors suffered from any health condition, especially visual acuity "<1/10" (n = 109), pituitary deficiency (n = 106), and neurocognitive impairment (n = 89). NF1 (HR 2.1) was associated with precocious puberty. With a median time post-diagnosis of 4.2 years, 33 cerebrovascular events were observed in 21 patients. CONCLUSIONS: Late relapses, second malignancies, and cerebrovascular diseases are severe late events resulting in premature mortality. Morbidity is high and needs after-cancer care to improve quality of life. Risk factors could be considered to better stratify long-term follow-up.

Excess healthcare expenditure in adults treated for solid cancer in childhood: a cohort study in France.

BACKGROUND: Due to late effects, childhood cancer survivors (CCS) are more likely to have multiple chronic conditions than the general population. However, little is known about the economic burden of care of CCS in the long term. OBJECTIVES: To estimate excess healthcare expenditure for long-term CCS in France compared to the general population and to investigate the associated factors. METHODS: We included 5353 5-year solid CCS diagnosed before the age of 21 years before 2000 from the French CCS cohort and obtained a random reference sample from the general population for each CCS, matched on age, gender and region of residence. We used the French national health data system to estimate annual healthcare expenditure between 2011 and 2018 for CCS and the reference sample, and computed the excess as the net difference between CCS expenditure and the median expenditure of the reference sample. We used repeated-measures linear models to estimate associations between excess healthcare expenditure and CCS characteristics. RESULTS: Annual mean (95% CI) excess healthcare expenditure was €3920 (3539; 4301), mainly for hospitalization (39.6%) and pharmacy expenses (17%). Higher excess was significantly associated with having been treated before the 1990s and having survived a central nervous system tumor, whereas lower excess was associated with CCS who had not received treatment with radiotherapy. CONCLUSIONS: Of the variables that influence excess healthcare expenditure, a lever for action is the type of treatment administered. Future research should focus on addressing the long-term cost-effectiveness of new approaches, especially those related to radiotherapy.

Post-treatment sperm cryopreservation practices in childhood and young adult cancer survivors.

RESEARCH QUESTION: What are current practices of post-treatment fertility preservation in male childhood cancer survivors (CCS) who have not benefitted from pre-therapeutic fertility preservation in France and other European countries? DESIGN: A survey was conducted of all fertility preservation centres in France (n = 30) and European fertility specialists (n = 9) in five European countries. Eight clinical cases and 40 questions were included to assess the effect of age at diagnosis, type of treatment (alkylating-agents, orchidectomy, testicular radiotherapy) and sperm parameters on the probability of a post-treatment fertility preservation proposal. Demographic characteristics of the responding practitioner were also collected. RESULTS: Post-treatment sperm cryopreservation was proposed by 100% of fertility specialists in cases of severe oligoasthenoteratozoospermia, 77-88% in cases of moderate oligoasthenoteratozoospermia and in 65-77% in cases of sperm motility and vitality impairment. In cases of normal sperm parameters, 27-54% of fertility specialists would propose post-treatment sperm cryopreservation. These results did not differ significantly according to the type of treatment received or to responder-related factors. Practices of European specialists were also guided by sperm parameter results; 44-67% of specialists responding that they would propose sperm cryopreservation in cases of moderate to severe sperm parameter alterations. CONCLUSION: Post-treatment semen analysis could be widely proposed to CCS who have not benefitted from pre-therapeutic fertility preservation. Post-treatment fertility preservation could be proposed in cases of persistent moderate to severe sperm parameter alterations. Guidelines would be important to homogenize practices and to encourage oncologists to refer CCS for fertility assessments.

Surveillance after childhood cancer: are survivors with an increased risk for cardiomyopathy regularly followed-up?

BACKGROUND: We aimed to study adherence to cardiac screening in long-term childhood cancer survivors (CCS) at high risk of cardiomyopathy. METHODS: This study involved 976 5-year CCS at high risk for cardiomyopathy from the French Childhood Cancer Survivor Study. Determinants of adherence to recommended surveillance were studied using multivariable logistic regression models. Association of attendance to a long-term follow-up (LTFU) visit with completion of an echocardiogram was estimated using a Cox regression model. RESULTS: Among participants, 32% had an echocardiogram within the 5 previous years. Males (adjusted RR [aRR] 0.71, 95% CI 0.58-0.86), survivors aged 36-49 (aRR 0.79, 95% CI 0.64-0.98), Neuroblastoma (aRR 0.53, 95% CI 0.30-0.91) and CNS tumour survivors (aRR 0.43, 95% CI 0.21-0.89) were less likely to adhere to recommended surveillance. Attendance to an LTFU visit was associated with completion of an echocardiogram in patients who were not previously adherent to recommendations (HR 8.20, 95% CI 5.64-11.93). CONCLUSIONS: The majority of long-term survivors at high risk of cardiomyopathy did not adhere to the recommended surveillance. Attendance to an LTFU visit greatly enhanced the completion of echocardiograms, but further interventions need to be developed to reach more survivors.

Predictive factors of long-term follow-up attendance in very long-term childhood cancer survivors.

BACKGROUND: Long-term follow-up (LTFU) clinics have been developed but only some childhood cancer survivors (CCS) attend long-term follow-up (LTFU). OBJECTIVE: To identify factors that influence LTFU attendance. METHODS: Five-year CCS treated for a solid tumor or lymphoma in Gustave Roussy before 2000, included in the FCCSS cohort (French Childhood Cancer Survivor Study), aged >18 years and alive at the date of the LTFU Clinic opening (January 2012) were invited to a LTFU visit. Factors associated with attendance at the LTFU clinic between 2012 and 2020 were estimated using logistic regression analyses. Analyses included different types of factors: clinical (tumor characteristics, cancer treatments, late effects), medical (medical expenses were used as a proxy of survivor's health status), social (deprivation index based on census-tract data relating to income, educational level, proportion of blue-collar workers, and unemployed people living in the area of residence), and spatial (distance to the LTFU clinic). RESULTS: Among 2341 CCS contacted (55% males, mean age at study, 45 years; SD ± 10 years; mean age at diagnosis, 6 years; SD ± 5 years), 779 (33%) attended at least one LTFU visit. Initial cancer-related factors associated with LTFU visit attendance were: treatment with both radiotherapy and chemotherapy (odds ratio [OR], 4.02; 95% CI, 2.11-7.70), bone sarcoma (OR, 2.43; 95% CI, 1.56-3.78), central nervous system primitive tumor (OR, 1.65; 95% CI, 1.02-2.67), and autologous hematopoietic cell transplant (OR, 2.07; 95% CI, 1.34-3.20). Late effects (OR, 1.70; 95% CI, 1.31-2.20), highest medical expenses (OR, 1.65; 95% CI, 1.22-2.22), living in the most advantaged area (OR vs. the most deprived area = 1.60; 95% CI, 1.15-2.22), and shorter distance from LTFU care center (<12 miles) also increased attendance. CONCLUSIONS: Patients who are apparently healthy as well as socially disadvantaged and living far away from the center are less likely to attend LTFU care. PLAIN LANGUAGE SUMMARY: Among 2341 adult childhood cancer survivors contacted between 2012 and 2020, 33% attended at least one long-term follow-up visit. Clinical factors related to attendance were multimodal treatment of first cancer (combining chemotherapy and radiotherapy), stem cell transplant, type of diagnosis (bone tumor and central nervous system primitive tumor), late effects (at least one disease among second malignancy, heart disease, or stroke), and highest medical expenses. In addition, the study identified social and spatial inequalities related to attendance, with independent negative effects of distance and social deprivation on attendance, even though the medical costs related to the long-term follow-up examinations are covered by the French social security system.

Risk factors for obesity in adulthood among survivors of childhood cancer.

OBJECTIVE: The aim of this study was to identify risk factors for obesity in childhood cancer survivors (CCSs). METHODS: The study included 3199 patients of the French Childhood Cancer Survivor Study cohort, with 303 patients with obesity who had returned the self-questionnaire. Analyses were adjusted for social deprivation index and sex. RESULTS: CCSs were less likely to have obesity (9.5%; 95% CI: 8.5%-10.5%) than expected from the general French population rates (12.5%; p = 0.0001). Nevertheless, brain tumor survivors were significantly more likely to develop obesity than the general French population (p = 0.0001). Compared with patients who did not receive radiotherapy to the pituitary gland, those who received a dose >5 Gy had an increased risk of obesity: relative risk 1.9 (95% CI: 1.2-3.1), 2.5 (95% CI: 1.7-3.7), and 2.6 (95% CI: 1.6-4.3), respectively, for participants with 6 to 20 Gy, 20 to 40 Gy, and ≥40 Gy of radiation. Etoposide administration significantly increased the risk of obesity (relative risk 1.7; 95% CI: 1.1-2.6). High social deprivation index was also a risk factor, just like BMI at diagnosis. CONCLUSIONS: Long-term follow-up of CCSs should include weight follow-up during adulthood.

Risk of Renal or Urinary Related Hospitalization in Survivors of Childhood Cancer: Results from the French Childhood Cancer Survivor Study.

BACKGROUND: Hospitalization rates can be used as an indirect indicator of the burden and severity of adverse health outcomes in childhood cancer survivors (CCS). We aimed to determine the long-term risks of hospitalization related to renal and urinary diseases among 5-year CCS. METHODS: The French Childhood Cancer Survivor Study cohort was linked with data from the French National Healthcare System database, which enabled the identification of hospitalizations related to renal or urinary diseases. Clinical and detailed treatment data were collected from medical records. Dose-volume histograms were estimated for all patients treated with radiotherapy. Standardized Hospitalization Ratios and absolute excess risks (AER) were calculated. Relative risks were estimated using Poisson regression. RESULTS: A total of 5,498 survivors were followed for 42,118 person-years (PY). Survivors experience 2.9 times more renal hospitalizations than expected in the general population, with an AER of 21.2/10,000 PY. Exposing more than 10% of the kidneys' volume to at least 20 Gray increases the risk of being hospitalized for renal causes by 2.2 (95% confidence interval, 1.3-3.6). Nephrectomized survivors treated with high doses of ifosfamide (>60 g/m²) have an extremely high risk of hospitalization for renal causes. Patients with comorbidities have about a 3-fold higher risk, and nephrectomized patients a 2-fold higher risk of being hospitalized for renal causes compared with other subjects. In the case of hospitalization for urinary causes, treatment by anthracycline administration was found to be associated with an almost 2-fold higher risk of hospitalization compared with the general population. CONCLUSIONS: These results support the need for careful monitoring of long-term renal diseases in survivors who have undergone nephrectomy, those treated with high doses of radiation (≥20 Gy) even to small volumes of the kidneys, and those with predisposing risk factors. IMPACT: This study provides new evidence with potential impact on surveillance guidelines related to dose-volume indicators associated with renal toxicity.

Long-term hospitalisations in survivors of paediatric solid tumours in France.

The late effects of treatments for childhood cancers may lead to severe and multiple health conditions requiring hospitalisation. We aimed to estimate the hospitalisation rate among childhood cancer survivors (CCS) in France, to compare them with the general population and to investigate the associated factors. We matched total of 5439 5-year solid CCS diagnosed before the age of 21 between 1945 and 2000 by sex, birth year and region of residence to 386,073 individuals of the French general population. After linkage with the national hospital discharge database, we estimated the relative hospitalisation rate (RHR), the absolute excess risks (AERs) and the relative bed-day ratio (RBDR) during 2006-2018. We used generalised linear models to estimate associations between hospitalisation and survivor characteristics. Overall, the RHR was 2.49 (95% confidence interval [CI] 2.46-2.52) and the RBDR was 3.49 (95% CI 3.46-3.51). We found that neoplasm-related hospitalisations had the highest AER (105.8 per 1000 person-years), followed by genitourinary system diseases (34.4 per 1000 person-years) and cardiovascular diseases (19.2 per 1000 person-years). In adjusted analysis, CCS treated with chemotherapy (risk ratio [RR] 1.62, 95% CI 1.53-1.70), radiotherapy (RR 2.11, 95% CI 1.99-2.24) or both (RR 2.59, 95% CI 2.46-2.73) had a higher risk of hospitalisation than the ones who had not received any of these treatments. CCS treated during the past decades by chemotherapy and/or radiotherapy now had a higher hospitalisation risk for all main categories of diagnosis than the general population. Prevention strategies and medical surveillance programmes may promote a long-term decrease in the hospitalisation rate among CSS.

The Psychological Consequences of the COVID-19 Pandemic in Adults Treated for Childhood Cancer.

BACKGROUND: Compared with the general population, childhood cancer survivors (CCS) could be at greater risk of psychological distress following the emergence of the COVID-19 pandemic. PURPOSE: This cross-sectional study assessed the psychological consequences of COVID-19 on the mental health of CCS. DESIGN AND PARTICIPANTS: In December 2020, we interviewed through an online self-report questionnaire, 580 5-year CCS participating in the French Childhood Cancer Survivor Study (FCCSS) cohort. METHODS: We first compared the mental health score of CCS with that observed in the French general population of the same age and gender. Subsequently, we studied predictors of the mental health score of CCS. RESULTS: External comparisons revealed that the mental health score of CCS was similar to that of the general population. Among CCS, almost 42% stated that their psychological state had been worse during the lockdown. Predictors of poorer mental health included, among others, female gender, reporting a change in the occupational situation, having a relative who had been hospitalized or had died following COVID-19, and a greater perceived infection risk. INTERPRETATION AND IMPLICATIONS: Given the pre-existing vulnerability of some CCS to mental distress, the additional psychological consequences of COVID-19 in vulnerable survivors should receive attention from health care providers.

An algorithm for identifying chronic kidney disease in the French national health insurance claims database.

BACKGROUND: Published algorithms for identifying chronic kidney disease in healthcare claims databases have poor performance except in patients with renal replacement therapy. We propose and describe an algorithm to identify all stage chronic kidney disease in a French healthcare claims databases and assessed its performance by using data from the Renal Epidemiology and Information Network registry and the French Childhood Cancer Survivor Study cohort. METHODS: A group of experts met several times to define a list of items and combinations of items that could be related to chronic kidney disease. For the French Childhood Cancer Survivor Study cohort, information on confirmed chronic kidney disease cases extracted from medical records was considered the gold standard (KDIGO definition). Sensitivity, specificity, and positive and negative predictive value and kappa coefficients were estimated. The contribution of each component of the algorithm was assessed for 1 and 2 years before the start of renal replacement therapy for confirmed end-stage kidney disease in the Renal Epidemiology and Information Network registry. RESULTS: The algorithm's sensitivity was 78%, specificity 97.4%, negative predictive value 98.4% and positive predictive value 68.7% in French Childhood Cancer Survivor Study cohort and the kappa coefficient was 0.79 for agreement with the gold standard. The algorithm 93.6% and 55.1% of confirmed incident end-stage kidney disease cases from the Renal Epidemiology and Information Network registry when considering 1 year and 2 years, respectively, before renal replacement therapy start. CONCLUSIONS: The algorithm showed good performance among younger patients and those with end-stage kidney disease in the twol last years prior to renal replacement therapy. Future research will address the ability of the algorithm to detect early chronic kidney disease stages and to classify the severity of chronic kidney disease.

Risk perceptions and health care use in the era of the COVID-19 pandemic in adults treated for childhood cancer.

PURPOSE: During the COVID-19 pandemic, childhood cancer survivors (CCS) may have felt more at risk of having severe consequences of COVID-19 and therefore may have been more likely to defer their health care use. We aimed to assess the risk perceptions of CCS related to COVID-19 (perceived infection risk, perceived risk of experiencing a severe illness in the event of infection), and their forgoing of health care during the year 2020. METHODS: In December 2020, we interviewed through an online self-report questionnaire 580 5-year CCS participating in the French Childhood Cancer Survivor Study (FCCSS) cohort. Combining clinical and patient-reported outcomes, we studied predictors of perceived risks related to COVID-19 and forgoing health care. RESULTS: Overall, 60% of respondents stated that COVID-19 could have severe consequences for their health if infected. Survivors with a cardiovascular disease and those who felt more at risk of being infected were more likely to think that COVID-19 could have severe health consequences for them. Moreover, 30% of respondents seeking care declared they had forgone at least one medical appointment in 2020. Forgoing medical appointments was more common among CCS who reported a deterioration in their financial situation in 2020 and those who felt more at risk of being infected. CONCLUSIONS: This study shows that a considerable proportion of survivors had forgone medical appointments because of the pandemic; forgoing care was more frequent among the most socioeconomically disadvantaged survivors. IMPLICATIONS FOR CANCER SURVIVORS: This study presents data hitherto absent in the literature and suggests the need to develop telehealth to ensure appropriate long-term follow-up of CCS.

Long-term follow-up of high-risk neuroblastoma survivors treated with high-dose chemotherapy and stem cell transplantation rescue.

Intensive treatments including high-dose chemotherapy (HDC) with autologous stem cell rescue have improved high-risk neuroblastoma (HRNB) survival. We report the long-term health status of 145 HRNB survivors, alive and disease-free 5 years post HDC. Median follow-up was 15 years (range = 5-34). Six patients experienced late relapses, 11 developed second malignant neoplasms (SMNs), and 9 died. Event-free and overall survivals 20 years post HDC were 82% (95% CI = 70%-90%) and 89% (78%-95%), respectively. Compared with the French general population, the standardized mortality ratio was 19 (95% CI = 8.7-36.1; p < 0.0001) and the absolute excess risk was 37.6 (19.2-73.5). Late effects were observed in 135/145 patients (median = 3 events/patient); 103 had at least one severe event. SMNs arose at a median of 20 years post HDC and included carcinoma (n = 5), sarcoma (2), acute myeloid leukemia (2), melanoma (1), and malignant glioma (1). Non-oncologic health events included dental maldevelopment (60%), severe hearing loss (20% cumulative probability at 15 years), hepatic focal nodular hyperplasia (14%), thyroid (11%), cardiac (8%), and renal (7%) diseases and growth retardation (height-for-age z-score ≤ -2 for 21%). Gonadal insufficiency was near-universal after busulfan (40/43 females, 33/35 males). Severe late effects are frequent and progressive in HRNB survivors needing systematic very long-term follow-up.

Risk of subsequent colorectal cancers after a solid tumor in childhood: Effects of radiation therapy and chemotherapy.

BACKGROUND: Very few previous studies have addressed the question of colorectal cancer (CRC) after childhood cancer treatment. We aimed to quantify the roles of radiation therapy and chemotherapy agents in the occurrence of subsequent CRC. METHODS: A nested case-control study was conducted using 36 CRC cases and 140 controls selected from 7032 five-year survivors of the French Childhood Cancer Survivor Study (FCCSS) cohort, treated from 1945 to 2000 in France. The radiation dose-distribution metrics at the site of CRC and doses of individual chemotherapeutic agents were calculated. Conditional logistic regressions were performed to calculate odds ratios (ORs). RESULTS: Overall, patients who received radiotherapy with estimated dose to colon had a 4.3-fold (95% CI, 1.3-17.6) increased risk for CRC compared with patients who did not receive radiotherapy, after adjustment for chemotherapy. This risk increased to 8.9-fold and 19.3-fold among patients who received radiation doses ranging from 20 to 29.99 Gy and ≥30 Gy, respectively. Our data reported a significantly elevated OR for anthracyclines, after controlling for radiotherapy and MOPP regimen. But, restricted analyses excluding patients who had received ≥30 Gy showed that only radiation doses ranging from 20 to 29.99 Gy produced a significant increase in subsequent CRC risk (OR = 7.8; 95% CI, 1.3-56.0), after controlling for anthracyclines and MOPP regimen. CONCLUSIONS: The risk of subsequent CRC was significantly increased after radiation dose (even < 30 Gy). This novel finding supports the need to update monitoring guidelines for CRC to optimize the long-term follow-up for subsequent CRC in survivors of childhood cancer.

The role of irradiated heart and left ventricular volumes in heart failure occurrence after childhood cancer.

BACKGROUND: Paediatric cancer survivors have a high risk of developing cardiac diseases, and the most frequent cardiac disease is heart failure (HF). The radiation dose-volume effects in the heart and cardiac substructures have not been explored in childhood cancer survivors (CCS). Therefore, the role of irradiated heart volume in the occurrence of HF among this population remains unclear. The aims of this study were to determine the doses and irradiated volumes of the heart and left ventricle (LV) related to the risk of HF in CCS and to investigate the impact of anthracycline exposure on this risk. METHODS AND RESULTS: A case-control study nested in the French Childhood Cancer Survivors Study cohort. The mean heart and left ventricular doses and volumes indicators were estimated by reconstruction of individual treatments. A total of 239 HF cases and 1042 matched controls were included. The median age of HF diagnosis was 25.1 years. The median volume of the heart that received ≥ 30 Gy was 61.1% for cases and 16.9% for controls. In patients who did not receive anthracycline, the risk of HF was increased 3.6-fold when less than 10% of the LV received ≥ 30 Gy when compared to patients who were not exposed to any cardiac radiation and anthracycline. CONCLUSIONS: Small irradiated volumes of the heart or LV were significantly associated with HF risk. To the author's knowledge, this is the first study to report a dose-response relationship based on dose-volume indicators in CCS, which can be translated efficiently into current clinical practice.

Breast Cancer, Secondary Breast Cancers in Childhood Cancer Male Survivors-Characteristics and Risks.

PURPOSE: Male breast cancer (MBC) is uncommon, accounting for less than 1% of all breast cancers. Secondary breast cancers among childhood cancer survivors have been well described in the literature, but less is known about MBC. METHODS AND MATERIALS: We carried out an analysis in a cohort of 7019 five-year survivors of a solid childhood (aged ≤20 years) cancer treated in France before 2001 and followed for an average of 20 years and compared breast cancers occurring in both men and women. RESULTS: Among the 7019 survivors, 4 out of 3893 male survivors developed breast cancer, compared with 99 out of 3126 female survivors. All of the men had a history of radiation therapy. The 4 men with MBC had estrogen receptors and 3 had progesterone receptors. CONCLUSIONS: MBC is a rare second malignancy among childhood cancer survivors. Receipt of radiation therapy is a recognized risk factor, but more data about eventual genetic mutations are necessary. Regular screening based only on a history of radiation therapy is not recommended; however, attention must be given in the case of suspicious symptoms.

Fecundity and Quality of Life of Women Treated for Solid Childhood Tumors Between 1948 and 1992 in France.

PURPOSE: To describe fecundity in female survivors of childhood cancer and consider the correlation with quality of life (QOL). MATERIALS AND METHODS: Of 1744 women treated for childhood cancer before the age of 15 years at one of eight French cancer treatment centers between 1948 and 1992, 1187 who were alive in 2005 were sent a self-administered questionnaire, including questions about health status, QOL (MOS SF-36), and fecundity. A standardized fecundity ratio (SFR) was calculated (SFR: observed/expected number of children) for each individual based on a national reference. RESULTS: Of the 972 individuals (82%) who responded, 53% had at least 1 child. The overall SFR, 0.65, was dependent upon the initial diagnosis, more decreased in Central Nervous System tumors (0.24; p < 10-3) than in Germ cell (0.46; p = 0.03) or Sympathetic Nervous System tumors (0.79; p = 0.02). The average QOL motor score was 72.5 ± 19.5, and the average mental score was 61.4 ± 16.7. After adjusting for age, pathology, and self-reported sequelae in the questionnaires, it was determined that SF-36 mental (p = 0.002) and motor (p < 0.0002) scores correlated positively with fecundity, and SF-36 scores correlated negatively with locomotor late effects (p < 0.0001), growth insufficiency (p = 0.002), and psychological disorders (p < 0.001). Gonadal insufficiency was correlated with neither motor nor mental scores. CONCLUSION: Women treated for childhood cancer demonstrated impaired fecundity that correlated with poor QOL, as registered by the SF-36. Patients should be warned of the risk of impaired fecundity early during the follow-up. If possible, preservation of fertility should be prioritized at initiation of therapy.

The right to be forgotten: a change in access to insurance and loans after childhood cancer?

PURPOSE: Access to insurance for a loan or a mortgage is an important issue for childhood cancer survivors. The aim of this study was to describe difficulties experienced by adult survivors. METHODS: A total of 1920 survivors treated before the age of 18 in five French cancer centers responded to a questionnaire in 2010. Survivors who had tried to obtain a loan were asked if they had experienced difficulties, which were defined as experiencing rejection, higher premiums, or exclusions. The questionnaire investigated health problems related to the circulatory, respiratory, digestive, urinary, endocrine, hormonal, and nervous systems. Second tumors, diabetes mellitus, cardiac disease, and stroke were ascertained from a physician's report or medical records. Multivariable analyses were conducted to identify the characteristics of survivors reporting difficulties. RESULTS: Difficulties were experienced by 10.4% of those who had tried to obtain a small loan (n = 787) and by 30.1% of those who had tried to obtain a home loan (n = 909). Disclosure of childhood cancer to the insurer and amputation surgery were negatively associated with insurance accessibility, even when controlling for age, gender, education, health-related unemployment, familial situation, and severe or life-threatening conditions such as cardiovascular diseases, second cancers, or diabetes. CONCLUSION: This study showed that the financial burden of cancer can extend decades after diagnosis. IMPLICATIONS FOR CANCER SURVIVORS: Thanks to a 2016 law, French cancer survivors no longer have to disclose their cancer to insurers after a fixed number of years. This law will probably lessen the socioeconomic burden of cancer.

Cerebrovascular Diseases in Childhood Cancer Survivors: Role of the Radiation Dose to Willis Circle Arteries.

BACKGROUND AND PURPOSE: The aim of this study was to investigate the role of radiation dose received to the circle of Willis (WC) during radiation therapy (RT) and of potential dose-response modifiers on the risk of stroke after treatment of childhood cancer. METHODS: We evaluated the risk factors for stroke in a cohort of 3172 5-year survivors of childhood cancer who were followed up for a median time of 26 years. Radiation doses to the WC and brain structures were estimated for each of the 2202 children who received RT. RESULTS: Fifty-four patients experienced a confirmed stroke; 39 were ischemic. Patients not receiving RT had a stroke risk similar to that of the general population, whereas those who received RT had an 8.5-fold increased risk (95% confidence interval [CI]: 6.3-11.0). The excess of incidence of stroke increased yearly. The dose of radiation to the WC, rather than to other brain structures, was found to be the best predictor of stroke. The relative risk was 15.7 (95% CI: 4.9-50.2) for doses of 40 Gy or more. At 45 years of age, the cumulative stroke incidence was 11.3% (95% CI: 7.1%-17.7%) in patients who received 10 Gy or more to the WC, compared with 1% expected from general population data. Radiation doses received to the heart and neck also increased the risk. Surgery for childhood brain cancer was linked to hemorrhagic strokes in these patients. CONCLUSION: The WC should be considered as a major organ at risk during RT for childhood brain cancers. The incidence of radiation-induced ischemic stroke strongly increases with long-term follow-up.

Screening for psychological distress in very long-term adult survivors of childhood cancer.

This study evaluated the prevalence of psychological distress (PD) in a cohort of 348 adult childhood cancer survivors with a very long-term follow-up and assessed the characteristics associated with this distress (cancer type, treatment, sex, age at diagnosis, self-reported late effects, social support, type of remembrance, time since the diagnosis, age at evaluation), assuming that with time since the diagnosis, the PD of survivors will approximate that of the general population. Before attending a long-term follow-up consultation, survivors were sent 3 questionnaires: the Brief Symptom Inventory-18, the Impact of Event Scale, and the Illness Worry Scale (IWS). During the visit, they were administered the Mini-International Neuropsychiatric Interview (MINI) by a psychologist. The mean age of the survivors was 38.5 years (18.1-65.8) at consultation, 7 years (0.0-18.0) at cancer diagnosis, and mean time since diagnosis was 31.5 years (8.8-56.1). Multiple regression analyses of the data collected from self-administered questionnaires confirmed that being female, living alone, and self-reported late effects were associated with the high scores for all scales. Negative remembrances and being accompanied to the clinic were associated with higher IWS scores. Unlike the initial hypothesis, the MINI showed that, compared with controls, survivors experienced a higher prevalence of anxiety and mood disorders even after a very long time since the diagnosis. These findings show that a substantial subset of survivors experiment a high prevalence of PD, higher than the general population, and should be screened for PD whatever the time since the diagnosis.

Educational and occupational outcomes of childhood cancer survivors 30 years after diagnosis: a French cohort study.

BACKGROUND: Although survival from childhood cancer has increased, little is known on the long-term impact of treatment late effects on occupational attainment or work ability. METHODS: A total of 3512 five-year survivors treated before the age of 19 years in 10 French cancer centres between 1948 and 2000 were identified. Educational level, employment status and occupational class of survivors were assessed by a self-reported questionnaire. These outcome measures were compared with sex-age rates recorded in the French population, using indirect standardisation. Paternal occupational class was also considered to control for the role of survivors' socioeconomic background on their achievement. Multivariable analyses were conducted to explore clinical characteristics associated with the outcomes. RESULTS: A total of 2406 survivors responded to the questionnaire and survivors aged below 25 years were included in the current analysis. Compared with national statistics adjusted on age and sex, male survivors were more likely to be college graduates (39.2% vs 30.9% expected; P<0.001). This higher achievement was not observed either for leukaemia or central nervous system (CNS) tumour survivors. Health-related unemployment was higher for survivors of CNS tumour (28.1% vs 4.3%; P<0.001) but not for survivors of other diagnoses. Survivors of non-CNS childhood cancer had a similar or a higher occupational class than expected. CONCLUSIONS: Survivors treated for CNS tumour or leukaemia, especially when treatment included cranial irradiation, might need support throughout their lifespan.