Re-irradiation of recurrent glioblastoma as part of a sequential multimodality treatment concept.

PURPOSE: The aim of this retrospective study was to evaluate survival outcomes in well-performing, mainly, young patients receiving a sequence of all available therapeutic options for relapsed glioblastoma, including re-irradiation. METHODS: We performed a retrospective analysis of 27 patients irradiated twice for glioblastoma between 2008 and 2016. In the first line, all had surgical treatment of the tumor followed by radiotherapy with a total dose of 60 Gy and temozolomide. All re-irradiated patients were treated with a total dose of 36 Gy in 12 fractions. The endpoints were death from glioblastoma or any cause, and toxicity after re-irradiation. RESULTS: The median follow-up of survivors was 35.6 months. At the time of analysis, 25 patients had died. The median time between first and second radiotherapy was 18.9 months (6.1-58.4). Re-irradiation was performed at different time points of first, second and third progression. The median overall survival after first diagnosis was 39.2 months. Five years after first surgery, nearly 20% of the patients were alive. CONCLUSION: Carefully planned re-irradiation of the brain is a safe therapy for recurrent glioblastoma. Younger and well-performing patients benefit from all available therapy options. Every patient should be discussed in a multidisciplinary setting at each time point of tumor progression. Further prospective studies are needed to define the optimal time, dose and volume of re-irradiation.

The TNM 8 M1b and M1c classification for non-small cell lung cancer in a cohort of patients with brain metastases.

BACKGROUND AND PURPOSE: According to the recent TNM 8 classification, patients with metastatic non-small cell lung cancer (NSCLC) and single extrathoracic metastasis should be classified as stage M1b, while those with 2 or more metastases comprise stage M1c. The purpose of this study was to analyze the impact of this classification in patients with brain metastases. MATERIALS AND METHODS: This retrospective study included 172 patients treated with individualized approaches. Actuarial survival was calculated. Uni- and multivariate analyses were performed. RESULTS: Thirty patients (17%) were staged as M1b. Those with squamous cell cancer were more likely to harbor M1b disease (29%, adenocarcinoma 14%, other histology 17%, p = 0.16). Median survival was 5.4 months (8.0 months in case of M1b disease and 4.5 months in case of M1c disease, p = 0.001). Multivariate analysis confirmed the role of M1b stage. M1b patients managed with upfront surgery or radiosurgery had significantly longer median survival than those who received whole-brain irradiation (21.0 vs. 3.5 months, p = 0.0001) and the potential to survive beyond 5 years. CONCLUSIONS: We found the M1b classification to provide clinically relevant information. The multivariate analysis suggested that patients with M1b disease, better performance status and younger age have better survival.

Colorectal cancer metastatic to the brain: analysis of prognostic factors and impact of KRAS mutations on presentation and outcome.

BACKGROUND: Treatment concepts for metastatic colorectal cancer continue to evolve. While the presence of RAS mutations impacts systemic therapy, little is known about the influence of such mutations in patients with brain metastases. PATIENTS AND METHODS: Pooled retrospective analysis was conducted of 57 patients with brain metastases from colorectal cancer treated in two different institutions (2005-2013). RESULTS: The only mutations analyzed in a relatively large subgroup were KRAS mutations (14 wild type, 12 mutated). Mutation status was not associated with baseline characteristics such as number or location of metastases, and did not impact prognosis. Three factors were significantly associated with survival in multivariate analysis: Karnofsky Performance Status (KPS), management strategy, and systemic treatment. Median survival was 0.6 months with best supportive care, 3.0 months with initial whole-brain radiotherapy (WBRT), and 12.7 months if initial treatment included surgery or stereotactic radiosurgery (SRS), p = 0.0001. The survival difference between the WBRT and surgery/SRS groups was largest in patients with KPS 80-100. CONCLUSION: Effective local treatment was a prerequisite for improved survival. The only significant prognostic baseline factor was KPS, which forms the basis of the diagnosis-specific graded prognostic assessment (DS-GPA) score. Thus, our results validate the DS-GPA in this patient population. So far, neither this nor other studies suggest a clinically important impact of KRAS mutations beyond their previously reported association with development of brain metastases. Studies focusing on patients who develop brain metastases early during the course of metastatic disease might be warranted, because the influence of different systemic therapies might be larger in this subgroup.

Does overall treatment time impact on survival after whole-brain radiotherapy for brain metastases?

PURPOSE To evaluate whether reduced overall treatment time (OTT), i.e., administration of more than 5 fractions per week, or uncompensated treatment interruption resulting in increased OTT influences survival of patients treated with whole-brain radiotherapy (WBRT) for brain metastases. METHODS Retrospective multi-institutional intention-to-treat study including 233 patients treated with primary WBRT (prescribed dose 10 fractions of 3 Gy; no previous SRS or surgery) administered over 10-38 days. Four groups were studied: OTT 10-11 vs. 12 days, 13-15 or >15 days. RESULTS Fourteen patients (6%) failed to complete WBRT and received 3-9 fractions (median 7). Their median survival was 0.5 months as compared to 3 months in patients who completed WBRT. No significant impact of OTT on survival was found. Median survival was 1.5, 2.9, 3.0 and 3.1 months in the four groups mentioned above. CONCLUSIONS Compensation for unintended treatment interruption is generally recommended but might not always be feasible. Depending on histological tumour type or expected repopulation, prognostic factors and neurological status, it might be acceptable to complete an interrupted course of WBRT without compensation in selected patients. While survival might be largely independent from OTT, it should also be evaluated whether this parameter has any impact on quality of life and duration of palliation.