Checkpoint inhibitors and radiation treatment in Hodgkin's lymphoma : New study concepts of the German Hodgkin Study Group.

BACKGROUND: Patients with classical Hodgkin's lymphoma (cHL) have a good prognosis even in advanced stages. However, combined chemo- and radiotherapy, as the standard of care, is also associated with treatment-related toxicities such as organ damage, secondary neoplasias, infertility, or fatigue and long-term fatigue. Many patients suffer from this burden although their cHL was cured. Therefore, the efficacy of immune checkpoint inhibitors like anti-PD1/PD-L1 antibodies in the treatment of solid cancers and also in HL offers new options. A remarkable and durable response rate with a favorable toxicity profile was observed in heavily pretreated cHL patients. METHODS: Planning to perform prospective randomized clinical trials in the content of radio-immune treatment in patients with Hodgkin's lymphoma (HL), we transferred the results of preliminary clinical studies and basic research in clinical relevant study concepts. RESULTS: Based on these promising early phase trial data, the German Hodgkin Study Group (GHSG) will investigate innovative treatment regimens in upcoming phase II trials. CONCLUSION: The therapeutic efficacy and potential synergies of anti-PD1 antibodies in combination with chemo- or radiotherapy will be investigated in various settings of HL.

Fertility and gonadal function in female survivors after treatment of early unfavorable Hodgkin lymphoma (HL) within the German Hodgkin Study Group HD14 trial.

BACKGROUND: In the HD14 trial, 2×BEACOPPescalated+2×ABVD (2+2) has improved the primary outcome. Compared with 4×ABVD, this benefit might be compromised by more infertility in women. Therefore, we analyzed gonadal function and fertility. PATIENTS AND METHODS: Women≤45 years in ongoing remission at least 1 year after therapy were included. Hormone parameters, menopausal symptoms, measures to preserve fertility, menstrual cycle, pregnancies, and offspring were evaluated. RESULTS: Three hundred and thirty one of 579 women addressed participated (57.2%) and 263 per-protocol treated patients qualified (A=ABVD: 137, B=2+2: 126, mean time after therapy 42 and 43 months, respectively). Regular menstrual cycle after treatment (A: 87%, B: 83%) and time to recovery (≤12 months) were not different. Follicle-stimulating hormone and anti-Muellerian hormone were significantly better in arm A. However, pregnancies after therapy favored arm B (A: 15%, B: 26%, P=0.043) and motherhood rates were equivalent to the German normal population. Multivariate analysis revealed prophylactic use of gonadotropin-releasing hormone (GnRH) analogues as highly significant prognostic factor for preservation of fertility (odds ratio=12.87, P=0.001). Severe menopausal symptoms were frequent in women≥30 years (A: 21%, B: 25%). CONCLUSIONS: Hormonal levels after 2+2 indicate a reduced ovarian reserve. However, 2+2 in combination with GnRH analogues does not compromise fertility within the evaluated observation time.

Salvage surgery for cervical radioiodine refractory 18F-FDG-PET positive recurrence of papillary thyroid cancer.

PURPOSE: Five percent of patients with differentiated thyroid cancer are diagnosed with radioiodine refractory relapse in the course of the disease. For isolated or oligometastatic cervical recurrence, resection or another local treatment is recommended. In this study, the impact of surgical treatment of cervical radioiodine refractory 18F-FDG-PET positive relapse of papillary thyroid cancer (PTC) was evaluated. METHODS: Patients receiving radioiodine therapy between 2005 and 2015 at the University Hospital of Cologne, Germany, for PTC were screened. The subgroup of patients undergoing surgery during the course of disease after recommendation by a multidisciplinary endocrine team for cervical radioiodine refractory 18F-FDG-PET positive recurrence was identified. Demographics, clinic-pathologic characteristics, oncologic treatment, and outcome were analyzed. RESULTS: Thirty (3%) of 969 patients with PTC treated with radioiodine therapy at our institution underwent surgery for radioiodine refractory 18F-FDG-PET positive cervical recurrence during the course of the disease. In eight (26.6%) patients, more than one operation was performed. Sixteen (53%) patients received external beam radiation therapy (EBRT) after surgery. Follow-up was on average, 79.2 ± 61.6 months after the last surgical treatment. Biochemical and radiological cure was seen in 12 (40%) patients. Remission was significantly more frequent in younger patients (P = 0.0001) with lymph node rather than soft tissue tumor recurrence (P = 0.004). CONCLUSIONS: Surgical treatment of radioiodine refractory 18F-FDG-PET positive cervical recurrence led to biochemical and radiological cure in about 40% of patients in this study. Further data are needed concerning risk stratification of potential subgroups benefitting of surgical approach and the possible role of EBRT after repetitive surgery.