Gonadal function in males after chemotherapy for early-stage Hodgkin's lymphoma treated in four subsequent trials by the European Organisation for Research and Treatment of Cancer: EORTC Lymphoma Group and the Groupe d'Etude des Lymphomes de l'Adulte.

Contains fulltext : 51705.pdf (publisher's version ) (Open Access)PURPOSE: To analyze fertility in male patients treated with various combinations of radiotherapy and chemotherapy, with or without alkylating agents, or with radiotherapy alone for Hodgkin's lymphoma. PATIENTS AND METHODS: Follicle-stimulating hormone (FSH) levels were measured in patients with early-stage upper-diaphragmatic disease enrolled in four European Organisation for Research and Treatment of Cancer (EORTC) trials (H6-H9). Median follow-up after therapy was 32 months. Patients with FSH measurement at least 12 months after end of treatment (n = 355) were selected to assess post-treatment fertility. Patients with FSH measurement 0 to 9 months after therapy (n = 349) were selected to analyze fertility recovery; of these, patients with elevated FSH (> 10 U/L; n = 101) were followed until recovery. Factors predictive for therapy-related infertility were assessed by logistic regression. RESULTS: The proportion of elevated FSH was 3% and 8% in patients treated with radiotherapy only or with nonalkylating chemotherapy (doxorubicin, bleomycin, vinblastine, dacarbazine [ABVD], epirubicin, bleomycin, vinblastine, prednisone [EBVP]); it was 60% (P < .001) after chemotherapy containing alkylating agents (mechlorethamine, vincristine, procarbazine, prednisone [MOPP], MOPP/doxorubicin, bleomycin, vinblastine [ABV], bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone [BEACOPP]). After a median time of 19 months, recovery of fertility occurred in 82% of patients treated without alkylating chemotherapy. This proportion was 30%, statistically (P < .001) lower in those treated with alkylating chemotherapy, and median time to recovery was 27 months. The post-treatment proportion of elevated FSH increased significantly (P < .001) with the dose of alkylating chemotherapy administered, and recovery was less frequent and slower after higher doses. Age more than 50 years and stage II disease also contributed to poor outcome. CONCLUSION: Fertility can be secured after nonalkylating chemotherapy for Hodgkin's lymphoma. In contrast, alkylating chemotherapy has a dismal effect, even after a limited number of cycles

Dentition patterns in bilateral cleft lip subphenotypes: multicenter study

OBJECTIVES: Here, we retrospectively investigated cases of bilateral oral clefts (OCs) to determine the clinical relevance of detailed distinction of incomplete cleft lip subphenotypes, based on morphological severity of the cleft, within the categories cleft lip with or without alveolus (CL ± A) and cleft lip, alveolus, and palate (CLAP). We further assessed possible associations between CL subphenotypes (complete vs different incomplete types) and different dentition patterns of the lateral incisor. MATERIALS AND METHODS: Our analysis included 151 non-syndromic Caucasian bilateral OC-patients (8-20 years old) from the Dutch Association for Cleft Palate and Craniofacial Anomalies registry. Six different deciduous and permanent lateral incisor patterns were distinguished: normal position (z/Z), supernumerary lateral incisor (n/N), presence in the anterior (x/X) or posterior (y/Y) segment of the cleft, one in each cleft segment (xy/XY), and agenesis (ab/AB). Logistic regression was performed to show the associations between the CL subphenotypes and dentition patterns of the lateral incisor. RESULTS: One hundred three had complete, while 48 had incomplete CLs. Patterns z/Z and n/N were associated with a submucous/vermillion notch, incomplete CL, and intact alveolus. Patterns x/X, y/Y, and xy/XY were most common in patients with two-thirds to subtotal CL and complete CL. The most severe pattern, ab/AB, was most commonly associated with complete CL. CONCLUSIONS: Based on the morphological severity of the CLs, it can be stated that the more severe the CL in bilateral CL ± A and CLAP, the more severe the abnormal pattern of the dentition. CLINICAL RELEVANCE: Further distinction of incomplete cleft lip subphenotypes (submucous/vermillion notch, one-third to two-thirds CL, two-thirds to subtotal CL) in bilateral CL ± A and CLAP has clinical relevance

Effects of intermittent and continuous exercise on energy expenditure, substrate utilization, and RMR in women

Background Cardiovascular disease after treatment is an important concern in cancer survivors. However, knowledge of cardiotoxicity is limited by the retrospective nature of data, which often does not contain details of treatment exposure. To facilitate individual risk counselling of patients, we aimed to quantify the effect of anthracyclines, vinca-alkaloids, and radiotherapy on the risk of cardiovascular disease in patients treated for Hodgkin's lymphoma. Methods In 2009-10, a Life Situation Questionnaire (LSQ) was distributed to patients by mail to assess late-onset effects of Hodgkin's lymphoma treatment in patients who were included in nine successive European Organisation for Research and Treatment of Cancer (EORTC) and the Groupe d'Etude des Lymphomes de l'Adulte (GELA, now renamed LYSA) randomised trials between 1964 and 2004. We reconstructed the mean radiation doses to the heart and carotid arteries and the cumulative doses of anthracyclines and vinca-alkaloids for all patients. Incidence of cardiovascular disease was reported during follow-up and updated through the LSQ. We applied Cox proportional hazards regression analyses to quantify the effect of chemotherapy and radiation on the risk of a first cardiovascular disease event. Findings Information of primary treatment was complete for 6039 patients (median age at diagnosis 30 years [IQR 23-40]; median length of follow-up 9 years [6-14]). 1919 patients responded to the LSQ. 1238 first cardiovascular events were recorded in 703 patients, most were ischaemic heart disease (132 [19%]), congestive heart failure (85 [12%]), arrhythmia (110 [16%]), and valvular disease (77 [11%]). The mean heart radiation dose per 1 Gy increase (HR 1.015 [95% CI 1.006-1.024], p = 0.0014) and the dose of anthracyclines per 50 mg/m(2) increase in cumulative dose (1.077 [1.021-1.137], p = 0.0064) were significant predictors of cardiovascular disease. Cumulative dose of vinblastine (unadjusted model p = 0.77), vincristine (p = 0.36), and mean radiation dose to the left (p = 0.41) or right (p = 0.70) internal carotid artery did not predict for cardiovascular events. Interpretation Quantification of the increased cardiovascular risk with specific doses of radiation and anthracycline exposure will enable a quantitative assessment of the optimum combination of systemic therapy and radiation, which will help clinicians to balance the risks and benefits of different regimens for individual patients