Cardiac Diseases Following Childhood Cancer Treatment: Cohort Study.

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.

Salvage radiotherapy with or without short-term hormone therapy for rising prostate-specific antigen concentration after radical prostatectomy (GETUG-AFU 16): a randomised, multicentre, open-label phase 3 trial.

BACKGROUND: How best to treat rising prostate-specific antigen (PSA) concentration after radical prostatectomy is an urgent clinical question. Salvage radiotherapy delays the need for more aggressive treatment such as long-term androgen suppression, but fewer than half of patients benefit from it. We aimed to establish the effect of adding short-term androgen suppression at the time of salvage radiotherapy on biochemical outcome and overall survival in men with rising PSA following radical prostatectomy. METHODS: This open-label, multicentre, phase 3, randomised controlled trial, was done in 43 French study centres. We enrolled men (aged ≥18 years) who had received previous treatment for a histologically confirmed adenocarcinoma of the prostate (but no previous androgen deprivation therapy or pelvic radiotherapy), and who had stage pT2, pT3, or pT4a (bladder neck involvement only) in patients who had rising PSA of 0·2 to less than 2·0 µg/L following radical prostatectomy, without evidence of clinical disease. Patients were randomly assigned (1:1) centrally via an interactive web response system to standard salvage radiotherapy (three-dimensional [3D] conformal radiotherapy or intensity modulated radiotherapy, of 66 Gy in 33 fractions 5 days a week for 7 weeks) or radiotherapy plus short-term androgen suppression using 10·8 mg goserelin by subcutaneous injection on the first day of irradiation and 3 months later. Randomisation was stratified using a permuted block method according to investigational site, radiotherapy modality, and prognosis. The primary endpoint was progression-free survival, analysed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT00423475. FINDINGS: Between Oct 19, 2006, and March 30, 2010, 743 patients were randomly assigned, 374 to radiotherapy alone and 369 to radiotherapy plus goserelin. Patients assigned to radiotherapy plus goserelin were significantly more likely than patients in the radiotherapy alone group to be free of biochemical progression or clinical progression at 5 years (80% [95% CI 75-84] vs 62% [57-67]; hazard ratio [HR] 0·50, 95% CI 0·38-0·66; p<0·0001). No additional late adverse events occurred in patients receiving short-term androgen suppression compared with those who received radiotherapy alone. The most frequently occuring acute adverse events related to goserelin were hot flushes, sweating, or both (30 [8%] of 366 patients had a grade 2 or worse event; 30 patients [8%] had hot flushes and five patients [1%] had sweating in the radiotherapy plus goserelin group vs none of 372 patients in the radiotherapy alone group). Three (8%) of 366 patients had grade 3 or worse hot flushes and one patient had grade 3 or worse sweating in the radiotherapy plus goserelin group versus none of 372 patients in the radiotherapy alone group. The most common late adverse events of grade 3 or worse were genitourinary events (29 [8%] in the radiotherapy alone group vs 26 [7%] in the radiotherapy plus goserelin group) and sexual disorders (20 [5%] vs 30 [8%]). No treatment-related deaths occurred. INTERPRETATION: Adding short-term androgen suppression to salvage radiotherapy benefits men who have had radical prostatectomy and whose PSA rises after a postsurgical period when it is undetectable. Radiotherapy combined with short-term androgen suppression could be considered as a reasonable option in this population. FUNDING: French Ministry of Health, AstraZeneca, and La Ligue Contre le Cancer.

Risk of second bone sarcoma following childhood cancer: role of radiation therapy treatment.

Bone sarcoma as a second malignancy is rare but highly fatal. The present knowledge about radiation-absorbed organ dose-response is insufficient to predict the risks induced by radiation therapy techniques. The objective of the present study was to assess the treatment-induced risk for bone sarcoma following a childhood cancer and particularly the related risk of radiotherapy. Therefore, a retrospective cohort of 4,171 survivors of a solid childhood cancer treated between 1942 and 1986 in France and Britain has been followed prospectively. We collected detailed information on treatments received during childhood cancer. Additionally, an innovative methodology has been developed to evaluate the dose-response relationship between bone sarcoma and radiation dose throughout this cohort. The median follow-up was 26 years, and 39 patients had developed bone sarcoma. It was found that the overall incidence was 45-fold higher [standardized incidence ratio 44.8, 95 % confidence interval (CI) 31.0-59.8] than expected from the general population, and the absolute excess risk was 35.1 per 100,000 person-years (95 % CI 24.0-47.1). The risk of bone sarcoma increased slowly up to a cumulative radiation organ absorbed dose of 15 Gy [hazard ratio (HR) = 8.2, 95 % CI 1.6-42.9] and then strongly increased for higher radiation doses (HR for 30 Gy or more 117.9, 95 % CI 36.5-380.6), compared with patients not treated with radiotherapy. A linear model with an excess relative risk per Gy of 1.77 (95 % CI 0.6213-5.935) provided a close fit to the data. These findings have important therapeutic implications: Lowering the radiation dose to the bones should reduce the incidence of secondary bone sarcomas. Other therapeutic solutions should be preferred to radiotherapy in bone sarcoma-sensitive areas.

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.

Impact of an information booklet on satisfaction and decision-making about BRCA genetic testing.

The aim of this study was to assess the impact of a standardized patient information booklet on decisions women make about genetic testing. This French national multi-centre survey included all women with cancer to whom genetic testing for BRCA1/2 mutation had been proposed. The control group was surveyed before the booklet became available (n = 263), and the experimental group, after being given it personally (n = 297). After multivariate adjustment, the booklet had a positive impact on satisfaction with the information provided (Odds ratio (OR) = 2.9; 99% confidence interval (CI) = 1.7-5.0; P = 0.001), decreased the decisional conflicts due to lack of information (OR = 1.9; 99% CI = 1.1-3.3; P = 0.002), and had a marginal impact on knowledge (R2-gain = 3%; P = 0.001). The women in the experimental group decided more frequently to undergo testing (99% vs. 95%; P = 0.009). In addition to a consultation providing more tailored information, a standardized written document improved the decision-making process involved in giving informed consent to genetic testing.

Thyroid adenomas after solid cancer in childhood.

PURPOSE: Very few childhood cancer survivor studies have been devoted to thyroid adenomas. We assessed the role of chemotherapy and the radiation dose to the thyroid in the risk of thyroid adenoma after childhood cancer. METHODS AND MATERIALS: A cohort of 3254 2-year survivors of a solid childhood cancer treated in 5 French centers before 1986 was established. The dose received by the isthmus and the 2 lobes of the thyroid gland during each course of radiation therapy was estimated after reconstruction of the actual radiation therapy conditions in which each child was treated as well as the dose received at other anatomical sites of interest. RESULTS: After a median follow-up of 25 years, 71 patients had developed a thyroid adenoma. The risk strongly increased with the radiation dose to the thyroid up to a few Gray, plateaued, and declined for high doses. Chemotherapy slightly increased the risk when administered alone but also lowered the slope of the dose-response curve for the radiation dose to the thyroid. Overall, for doses up to a few Gray, the excess relative risk of thyroid adenoma per Gray was 2.8 (90% CI: 1.2-6.9), but it was 5.5 (90% CI: 1.9-25.9) in patients who had not received chemotherapy or who had received only 1 drug, and 1.1 (90% CI: 0.4-3.4) in the children who had received more than 1 drug (P=.06, for the difference). The excess relative risk per Gray was also higher for younger children at the time of radiation therapy than for their older counterparts and was higher before attaining 40 years of age than subsequently. CONCLUSIONS: The overall pattern of thyroid adenoma after radiation therapy for a childhood cancer appears to be similar to that observed for thyroid carcinoma.

Phase III trial of protracted compared with split-course chemoradiation for esophageal carcinoma: Federation Francophone de Cancerologie Digestive 9102.

PURPOSE: Chemoradiotherapy (CRT) is an alternative to surgery for resectable locally advanced esophageal carcinoma (RLA-EC). We investigated the heterogeneity of the treatment benefits across subgroups of patients, defined according to the radiation scheme. PATIENTS AND METHODS: Between February 1993 and December 2000, 451 patients were enrolled. The following two schemes were allowed: protracted radiotherapy (P-RT), which scheduled 46 Gy over 4.5 weeks or split-course radiotherapy (SC-RT) with two 1-week courses of 15 Gy. Two courses of cisplatin and fluorouracil were delivered concomitantly. In case of exclusive CRT, a further course of 20 Gy over 2 weeks in the P-RT group and one 1-week course of 15 Gy in the SC-RT group were delivered with three courses of chemotherapy. SC-RT and P-RT were administered to 285 patients (64%) and 161 patients (36%), respectively. RESULTS: For P-RT versus SC-RT, the response rate to induction CRT was 67% v 68%, respectively (P = .09), and 2-year local relapse-free survival rate was 76.7% v 56.8%, respectively (P = .002). Shorter tumor length and P-RT were associated with better local control in multivariate analysis (P = .002 for both). After a median follow-up time of 47.4 months, 2-year overall survival rate was 37.1% for P-RT compared with 30.5% for SC-RT (P = .25). Independent prognostic factors on survival were tumor diameter (P = .02), weight loss of 10% or less (P = .05), and response to induction CRT (P = .002). CONCLUSION: Patients with RLA-EC treated with P-RT had better local control than patients treated with SC-RT. Response to induction CRT is a determinant prognostic factor on survival.

Patients' characteristics and rate of Internet use to obtain cancer information.

The aim of this study was to present baseline data on the access to Internet by French breast cancer patients attending genetic clinics and to examine factors affecting Internet health-related use. Twenty-four percent of participants used Internet to obtain information about the disease. This rate was higher among patients with health occupations [adjusted odds ratio (adjOR) 2.6; 95% confidence interval (CI) 1.3-5.1], the most highly educated (adjOR 2.1; 95% CI 1.1-4.0) and those under 41 years of age (adjOR 7.3; 95% CI 2.1-26.2). Almost one of every three women was dissatisfied of this source of information.