Intraoperative radiotherapy after resection of brain metastases located in the posterior fossa. Analysis of postoperative morbidity and mortality in a single center cohort.

INTRODUCTION: In order to improve surgical outcome and accelerate the adjuvant oncologic therapy, intraoperative Radiotherapy (IORT) has become a treatment option in oncologic surgery for various diseases including glioma and brain metastasis (BM). BMs are often located in the cranial posterior fossa (PF) requiring specific surgical considerations due to its complex anatomy. Up until now, data on IORT for BMs is limited and detailed description in the use of IORT for lesions in the PF is lacking. Our aim is to provide more insight into this emerging treatment strategy. METHODS: We performed a retrospective analysis of patients receiving surgery for BMs and undergoing IORT at our institution. Each patient was discussed at the interdisciplinary tumor board decision before the intervention. Patient characteristics, functional status (Karnofsky Performance Score, KPS) before and after surgery, disease (recursive partitioning analysis, lesion size) and operative parameters were analyzed. Adverse events (AE) were recorded up until 30 days after the intervention and rated according to the Clavien Dindo Rating scale. RESULTS: Nine patients (5 female) were included. None underwent prior radiotherapy (RT). Mean age was 66 ± 11 years. Preoperative median KPS was 80%. Mean BM diameter was 3.2 ± 0.9 cm. There was no statistically significant deterioration of the functional status after the intervention. Two patients experienced AEs with both of them needing revision surgery. CONCLUSION: Surgery for BMs with IORT in the PF seems safe and feasible. Further studies are needed to evaluate the influence of IORT on long-term outcome after BM surgery.

Resection of supratentorial brain metastases with intraoperative radiotherapy. Is it safe? Analysis and experiences of a single center cohort.

Introduction: Intraoperative Radiotherapy (ioRT) is an emerging treatment option in oncologic surgery for various diseases including intraaxial brain lesions to improve surgical outcome and accelerate the adjuvant oncologic therapy. Despite its use in glioma surgery, the application and data regarding ioRT in the treatment of brain metastases (BMs) is sparse. Here were report the largest series of supratentorial BMs treated with resection and ioRT according to functional outcome and adverse events. Methods: We performed a retrospective chart review analysis of patients undergoing surgery for BMs following an interdisciplinary tumor board decision in every case with ioRT at our institution. Patient properties, functional status (Karnofsky Performance Score/KPS) before and after surgery as well as oncologic (disease, recursive partitioning analysis, lesion size) and operative parameters were analyzed until hospital discharge. Adverse events (AE) were recorded until 30 days after surgery and rated according to the Clavien Dindo Grading (CDG) scale. Results: 70 patients (40 female) with various oncologic diseases were identified and analyzed. Six underwent prior RT. Mean age was 66 ± 11 years. Preoperative median KPS was 80% with a mean BM volume of 3.2 ± 1.2 cm3. Nine patients (13%) experienced in total 14 AEs, including 2 cases (3%) of postoperative death (CDG5) and 2 with new postoperative epilepsy necessitating additional pharmacotreatment (CDG2). Five patients suffered from new neurologic deficit (CDG1) not needing further surgical or medical treatment. After surgery, the neurological status in 7 patients (10%) deteriorated while it improved in 21 cases (30%). Patients experiencing AEs had longer hospitalization and poorer postoperative KPS mdn. 90 vs. 80%. There was no statistically significant deterioration of the functional status during the immediate postoperative course in the whole patient cohort. Conclusion: Surgery for supratentorial BMs with ioRT seems safe and feasible. Further studies on the benefit regarding oncologic outcome need to be performed.

Evaluation of Prognostic Factors and Role of Participation in a Randomized Trial or a Prospective Registry in Pediatric and Adolescent Nonmetastatic Medulloblastoma - A Report From the HIT 2000 Trial.

PURPOSE: We aimed to compare treatment results in and outside of a randomized trial and to confirm factors influencing outcome in a large retrospective cohort of nonmetastatic medulloblastoma treated in Austria, Switzerland and Germany. METHODS AND MATERIALS: Patients with nonmetastatic medulloblastoma (n = 382) aged 4 to 21 years and primary neurosurgical resection between 2001 and 2011 were assessed. Between 2001 and 2006, 176 of these patients (46.1%) were included in the randomized HIT SIOP PNET 4 trial. From 2001 to 2011 an additional 206 patients were registered to the HIT 2000 study center and underwent the identical central review program. Three different radiation therapy protocols were applied. Genetically defined tumor entity (former molecular subgroup) was available for 157 patients. RESULTS: Median follow-up time was 7.3 (range, 0.09-13.86) years. There was no difference between HIT SIOP PNET 4 trial patients and observational patients outside the randomized trial, with 7 years progression-free survival rates (PFS) of 79.5% ± 3.1% versus 78.7% ± 3.1% (P = .62). On univariate analysis, the time interval between surgery and irradiation (≤ 48 days vs ≥ 49 days) showed a strong trend to affect PFS (80.4% ± 2.2% vs 64.6% ± 9.1%; P = .052). Furthermore, histologically and genetically defined tumor entities and the extent of postoperative residual tumor influenced PFS. On multivariate analyses, a genetically defined tumor entity wingless-related integration site-activated vs non-wingless-related integration site/non-SHH, group 3 hazard ratio, 5.49; P = .014) and time interval between surgery and irradiation (hazard ratio, 2.2; P = .018) were confirmed as independent risk factors. CONCLUSIONS: Using a centralized review program and risk-stratified therapy for all patients registered to the study center, outcome was identical for patients with nonmetastatic medulloblastoma treated on and off the randomized HIT SIOP PNET 4 trial. The prognostic values of prolonged time to RT and genetically defined tumor entity were confirmed.

Hyperfractionated accelerated chemoradiation with concurrent fluorouracil-mitomycin is more effective than dose-escalated hyperfractionated accelerated radiation therapy alone in locally advanced head and neck cancer: final results of the radiotherapy cooperative clinical trials group of the German Cancer Society 95-06 Prospective Randomized Trial.

PURPOSE: To report the results and corresponding acute and late reactions of a prospective, randomized, clinical study in locally advanced head and neck cancer comparing concurrent fluorouracil (FU) and mitomycin (MMC) chemotherapy and hyperfractionated accelerated radiation therapy (C-HART; 70.6 Gy) to hyperfractionated accelerated radiation therapy alone (HART; 77.6 Gy). PATIENTS AND METHODS: Three hundred eighty-four stage III (6%) and IV (94%) oropharyngeal (59.4%), hypopharyngeal (32.3%), and oral cavity (8.3%) cancer patients were randomly assigned to receive either 30 Gy (2 Gy every day) followed by 1.4 Gy bid to a total of 70.6 Gy concurrently with FU (600 mg/m(2), 120 hours continuous infusion) days 1 through 5 and MMC (10 mg/m(2)) on days 5 and 36 (C-HART) or 14 Gy (2 Gy every day) followed by 1.4 Gy bid to a total dose of 77.6 Gy (HART). The data were analyzed on an intent-to-treat basis. RESULTS: At 5 years, the locoregional control and overall survival rates were 49.9% and 28.6% for C-HART versus 37.4% and 23.7% for HART, respectively (P = .001 and P = .023, respectively). Progression-free and freedom from metastases rates were 29.3% and 51.9% for C-HART versus 26.6% and 54.7% for HART, respectively (P = .009 and P = .575, respectively). For C-HART, maximum acute reactions of mucositis, moist desquamation, and erythema were lower than with HART, whereas no differences in late reactions and overall rates of secondary neoplasms were observed. CONCLUSION: C-HART (70.6 Gy) is superior to dose-escalated HART (77.6 Gy) with comparable or less acute reactions and equivalent late reactions, indicating an improvement of the therapeutic ratio.