Marianne Riepenhausen

Late valvular and other cardiac diseases after different doses of mediastinal radiotherapy for hodgkin disease in children and adolescents: Report from the longitudinal GPOH follow‐up project of the German–Austrian DAL‐HD studies

To analyze the impact of mediastinal irradiation on the incidence of cardiac late effects in long‐term survivors of pediatric Hodgkin disease (HD).

Breast Cancer in Young Women After Treatment for Hodgkin’s Disease During Childhood or Adolescence: An Observational Study With up to 33-Year Follow-up

BACKGROUND The treatment of Hodgkins disease (HD; also called Hodgkins lymphoma) in children and adolescents with radiotherapy and chemotherapy leads to high survival rates but has a number of late effects. The most serious one is the development of a secondary malignant tumor, usually in the field that was irradiated. In women, breast cancer can arise in this way. METHOD Data on the occurrence of secondary breast cancer (sBC) were collected from 590 women who were treated in five consecutive pediatric HD treatment studies in the years 1978-1995 and then re-evaluated in a late follow-up study after a median interval of 17.8 years (maximum, 33.7 years). Information was obtained from 1999 onward by written inquiry to the participants and their treating physicians. The cumulative incidence of sBC was calculated by the Gooley method. RESULTS By July 2012, sBC had been diagnosed in 26 of 590 female HD patients; the breast cancer was in the irradiated field in 25 of these 26 patients. Their age at the time of treatment for HD was 9.9 to 16.2 years (the pubertal phase), and sBC was discovered with a median latency of 20.7 years after HD treatment (shortest latency, 14.3 years) and at a median age of 35.3 years (youngest age, 26.8 years). The radiation dose to the supradiaphragmatic fields ranged from 20 to 45 Gy. The cumulative incidence for sBC 30 years after treatment for HD was 19% (95% confidence interval, 12% to 29%). For women aged 25 to 45 in this series, the frequency of breast cancer was 24 times as high as in the corresponding normal population. CONCLUSION Women who were treated for HD in childhood or adolescence have an increased risk of developing breast cancer as young adults. The risk is associated with prior radiotherapy and with the age at which it was administered (the pubertal phase). Because of these findings, a structured breast cancer screening project for this high-risk group has been initiated in collaboration with the German Consortium for Hereditary Breast and Ovarian Cancer (Deutsches Konsortium für familiären Brust- und Eierstockkrebs).

The Challenge of Pediatric Hodgkin's Disease–Where is the Balance Between Cure and Long-Term Toxicity?: A report of the West German multicenter studies DAL-HD-78, DAL-HD-82 and DAL-HD-85

From June 1978 until December 1989 more than 600 children under the age of 16 were treated for Hodgkins disease in West Germany. In three consecutive multicenter studies (DAL-HD-78, HD-82, HD-85) a combined modality treatment concept was used. The aim of all these studies was to reduce the total dose and the extent of radiotherapy as well as the intensity of chemotherapy. In addition, the invasive abdominal staging procedures and the indications for splenectomy were reappraised, so that the number of laparotomies and splenectomies could be restricted to cases with an high probability of abdominal and/or splenic involvement. Special attention was directed to the effects of radio-and chemotherapy on thyroid and gonadal function as well as the development of secondary malignancies. We conclude, that patients treated for Hodgkins disease with the combined modality treatment regimen (HD-78, HD-82), which included procarbazine, had a high probability of long term survival in first continuous complete remission (CCR). Omitting procarbazine (HD-85) significantly reduced the number of patients in first CCR in stages IIB to IV demonstrating the efficacy of this drug in the treatment of Hodgkins disease. On the other hand, procarbazine appeared to be the major gonadotoxic drug causing predominantly testicular injury affecting mainly spermatogenesis. Few secondary malignancies have been observed, until now, however long term follow-up will be needed, to document side effects as well as the efficacy of the different therapeutic regimen.

Parenthood in adult female survivors treated for Hodgkin's lymphoma during childhood and adolescence: a prospective, longitudinal study.

BACKGROUND Little is known about parenthood in women who were treated for Hodgkins lymphoma during childhood and adolescence. We aimed to assess the frequency of parenthood in female survivors of Hodgkins lymphoma younger than 18 years at diagnosis, and to compare it with that in a female population control group. METHODS In this prospective, longitudinal study, our cohort consisted of 590 female patients younger than 18 years at diagnosis who participated in one of five Hodgkins lymphoma treatment studies between June 19, 1978, and July 12, 1995. Women who had been followed up for 5 years or longer, were in continuous complete remission, and had no second malignancy or Hodgkins lymphoma relapse before parenthood were included in our parenthood analysis. Parenthood was defined as the delivery of a liveborn child. Frequency of parenthood was compared with that in the German female population aged 16-49 years, using data from the 2012 Mikrozensus population survey. We assessed parenthood by estimating cumulative incidences and hazard ratios (HRs) with associated variables. FINDINGS 467 of 590 patients in our cohort had long-term follow-up (median 20·4 years [IQR 16·3-24·8]) and were in continuous complete remission. 228 (49%) of 467 patients had 406 children (median of 1·78 children per mother, range 1-7). Cumulative incidences of parenthood were 67% (95% CI 64-75) at 27·7 years of follow-up (the longest number of years that a patient was followed up before she had her first child) and 69% (61-74) at 39·8 years of age (the oldest age of a patient before she had her first child). The incidence of parenthood did not differ between our cohort and the female German population for any age group up to 49 years, except for the 66 women aged 40-44 years at the time of last information, who had a significantly lower frequency of parenthood compared with the general population (40 [61%] of 66 vs 2,208,000 [78%] of 2,847,000; p=0·001). Procarbazine in cumulative doses up to 11,400 mg/m(2), cyclophosphamide in cumulative doses up to 6000 mg/m(2), alkylating agent dose scores of 1-5, therapy group based on disease stage at diagnosis, abdominal and supradiaphragmatic radiation, and age at treatment had no significant or only minor effects on parenthood. Parenthood was significantly reduced in survivors receiving pelvic radiation compared with those who received abdominal and supradiaphragmatic radiation (HR 0·76, 95% CI 0·61-0·95; p=0·01). INTERPRETATION The results of this study document an overall favourable prognosis for parenthood in female survivors of Hodgkins lymphoma. They will assist counselling of female survivors about their positive potential for future parenthood. FUNDING Deutsche Kinderkrebsstiftung, Jens-Brunken-Stiftung für Leukämie und Lymphomforschung, and Kinderkrebshilfe Münster.