Abstract 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.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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.
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BACKGROUND—Cardiac disease (CD) is one of the major side effects of childhood cancer therapy, but until now little has been known about the relationship between the heart radiation dose (HRD) ...received during childhood and the risk of CD.
METHODS AND RESULTS—The cohort comprised 3162 5-year survivors of childhood cancer. Chemotherapy information was collected and HRD was estimated. There were 347 CDs in 234 patients, 156 of them were rated grade ≥3. Cox and Poisson regression models were used. The cumulative incidence of any type of CD at 40 years of age was 11.0% (95% confidence interval CI, 9.5–12.7) and 7·4% (95% CI, 6.2–8.9) when only the CDs of grade ≥3 were considered. In comparison with patients who received no anthracycline and either no radiotherapy or an HRD<0·1Gy, the risk was multiplied by 18·4 (95% CI, 7.1–48.0) in patients who had received anthracycline and no radiotherapy or a HRD <0.1Gy, by 60.4 (95% CI, 22.4–163.0) in those who had received no anthracycline and an HRD≥30Gy, and 61.5 (95% CI, 19.6–192.8) in those who had received both anthracycline and an HRD≥30Gy.
CONCLUSIONS—Survivors of childhood cancers treated with radiotherapy and anthracycline run a high dose-dependent risk of developing CD. CDs develop earlier in patients treated with anthracycline than in those treated without it.
Radiotherapy and chemotherapy are associated with an increased risk of second malignant neoplasm (SMN). An association between SMN and familial aggregation has also been shown. The aim of this study ...was to investigate the role of familial factors in the risk of SMN and their potential interaction with the effect of treatment.
We devised a case-control study of 25 children with SMN (cases) and 96 children with no SMN after a cancer treatment (controls), taken from a cohort of 649 children treated at our institution between 1953 and 1985. A complete family history was obtained for patients and controls and a familial index defined to evaluate the degree of familial aggregation. The radiation dose given at 151 sites in the body was estimated for each radiotherapy course for each child.
Among family members of the 25 SMN cases, there were ten with early-onset (≤45 years) cancer, compared with eight among relatives of the 96 controls. Compared with patients who had no family history of early-onset cancer, those with one or more affected family members had an odds ratio for SMN of 4·7 (95% Cl 1·3–17·1; p=0·02). Adjustment for local radiation dose and exclusion of patients known to be predisposed to SMN (carriers of p53 mutation and those with Recklinghausen's disease) did not affect this risk substantially.
Both genetic factors and exposure to ionising radiation have independent effects on the risk of SMN. Follow-up of children treated for cancer should be especially vigilant when there is a family history of early-onset cancer.
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DOBA, GEOZS, IJS, IMTLJ, IZUM, KILJ, KISLJ, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SIK, UILJ, UKNU, UL, UM, UPCLJ, UPUK, VSZLJ
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.
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.
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.
Survivors treated for CNS tumour or leukaemia, especially when treatment included cranial irradiation, might need support throughout their lifespan.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Long-term follow-up (LTFU) clinics have been developed but only some childhood cancer survivors (CCS) attend long-term follow-up (LTFU).
To identify factors that influence LTFU attendance.
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).
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.
Patients who are apparently healthy as well as socially disadvantaged and living far away from the center are less likely to attend LTFU care.
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.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Background
Survivors of Hodgkin lymphoma (HL) in childhood have an increased risk of subsequent malignant neoplasms (SMNs). Herein, the authors extended the follow‐up of a previously reported Late ...Effects Study Group cohort and identified patients at highest risk for SMNs to create evidence for risk‐based screening recommendations.
Methods
The standardized incidence ratio was calculated using rates from the Surveillance, Epidemiology, and End Results program as a reference. The risk of SMN was estimated using proportional subdistribution hazards regression. The cohort included 1136 patients who were diagnosed with HL before age 17 years between 1955 and 1986. The median length of follow‐up was 26.6 years.
Results
In 162 patients, a total of 196 solid SMNs (sSMNs) were identified. Compared with the general population, the cohort was found to be at a 14‐fold increased risk of developing an sSMN (95% confidence interval, 12.0‐fold to 16.3‐fold). The cumulative incidence of any sSMN was 26.4% at 40 years after a diagnosis of HL. Risk factors for breast cancer among females were an HL diagnosis between ages 10 years and 16 years and receipt of chest radiotherapy. Males treated with chest radiotherapy at age <10 years were found to be at highest risk of developing lung cancer. Survivors of HL who were treated with abdominal/pelvic radiotherapy and high‐dose alkylating agents were found to be at highest risk of developing colorectal cancer and females exposed to neck radiotherapy at age <10 years were at highest risk of thyroid cancer. By age 50 years, the cumulative incidence of breast, lung, colorectal, and thyroid cancer was 45.3%, 4.2%, 9.5%, and 17.3%, respectively, among those at highest risk.
Conclusions
Survivors of childhood HL remain at an increased risk of developing sSMNs. In the current study, subgroups of survivors of HL at highest risk of specific sSMNs were identified, and evidence for screening provided.
Additional follow‐up of the large cohort in the current study has demonstrated that survivors of childhood Hodgkin lymphoma remain at an increased risk of solid subsequent malignant neoplasms. Subgroups of survivors of Hodgkin lymphoma at highest risk of specific solid subsequent malignant neoplasms are identified, and evidence for screening in high‐risk subgroups is provided.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
STUDY QUESTION
What is the effect of different alkylating agents used without pelvic radiation to treat childhood cancer in girls on the ovarian reserve in survivors?
SUMMARY ANSWER
Ovarian reserve ...seems to be particularly reduced in survivors who received procarbazine (in most cases for Hodgkin lymphoma) or high-dose chemotherapy; procarbazine but not cyclophosphamide dose is associated with diminished ovarian reserve.
WHAT IS KNOWN ALREADY
A few studies have demonstrated diminished ovarian reserve in survivors after various combination therapies, but the individual role of each treatment is difficult to assess.
STUDY DESIGN
Prospective cross-sectional study, involving 105 survivors and 20 controls.
PARTICIPANTS/MATERIALS, SETTING, METHODS
One hundred and five survivors aged 17–40 years and 20 controls investigated on Days 2–5 of a menstrual cycle or Day 7 of an oral contraceptive pill-free interval. Main outcome measures: ovarian surface area (OS), total number of antral follicles (AFC), serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol and anti-Müllerian hormone (AMH).
MAIN RESULTS AND THE ROLE OF CHANCE
Survivors had a lower OS than controls: 3.5 versus 4.4 cm2 per ovary (P = 0.0004), and lower AMH levels: 10.7 versus 22 pmol/l (P = 0.003). Ovarian markers (OS, AMH, AFC) were worse in patients who received high-dose compared with conventional-dose alkylating agents (P = 0.01 for OS, P = 0.002 for AMH, P < 0.0001 for AFC). Hodgkin lymphoma survivors seemed to have a greater reduction in ovarian reserve than survivors of leukaemia (P = 0.04 for AMH, P = 0.01 for AFC), sarcoma (P = 0.04 for AMH, P = 0.04 for AFC) and other lymphomas (P = 0.04 for AFC). A multiple linear regression analysis showed that procarbazine but not cyclophosphamide nor ifosfamide dose was associated with reduced OS (P = 0.0003), AFC (P = 0.0007), AMH (P < 0.0001) and higher FSH levels (P < 0.0001).
LIMITATIONS, REASONS FOR CAUTION
The small percentage of participating survivors (28%) from the total cohort does not allow conclusion on fertility issues because of possible response bias. The association between procarbazine and HL makes it impossible to dissociate their individual impacts on ovarian reserve. The number of controls is small, but ovarian volume and AMH levels in survivors were compared with published normal values and results were unchanged.
WIDER IMPLICATIONS OF THE FINDINGS
Early detection and follow-up of compromised ovarian function after cancer therapy should help physicians to counsel young survivors about their fertility window. However, longitudinal follow-up is required to determine the rate of progression from low ovarian reserve to premature ovarian failure.
STUDY FUNDING/COMPETING INTEREST(S)
La Ligue contre le Cancer (grant no., PRAYN7497). The authors have no competing interests to disclose.
Ewing sarcoma, a pediatric tumor characterized by EWSR1-ETS fusions, is predominantly observed in populations of European ancestry. We performed a genome-wide association study (GWAS) of 401 French ...individuals with Ewing sarcoma, 684 unaffected French individuals and 3,668 unaffected individuals of European descent and living in the United States. We identified candidate risk loci at 1p36.22, 10q21 and 15q15. We replicated these loci in two independent sets of cases and controls. Joint analysis identified associations with rs9430161 (P = 1.4 × 10(-20); odds ratio (OR) = 2.2) located 25 kb upstream of TARDBP, rs224278 (P = 4.0 × 10(-17); OR = 1.7) located 5 kb upstream of EGR2 and, to a lesser extent, rs4924410 at 15q15 (P = 6.6 × 10(-9); OR = 1.5). The major risk haplotypes were less prevalent in Africans, suggesting that these loci could contribute to geographical differences in Ewing sarcoma incidence. TARDBP shares structural similarities with EWSR1 and FUS, which encode RNA binding proteins, and EGR2 is a target gene of EWSR1-ETS. Variants at these loci were associated with expression levels of TARDBP, ADO (encoding cysteamine dioxygenase) and EGR2.
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