The study group.

The management of patients with brain metastases has become a major issue due to the increasing frequency and complexity of the diagnostic and therapeutic approaches. In 2014, the European Association of Neuro-Oncology (EANO) created a multidisciplinary Task Force to draw evidence-based guidelines for patients with brain metastases from solid tumors. Here, we present these guidelines, which provide a consensus review of evidence and recommendations for diagnosis by neuroimaging and neuropathology, staging, prognostic factors, and different treatment options. Specifically, we addressed options such as surgery, stereotactic radiosurgery/stereotactic fractionated radiotherapy, whole-brain radiotherapy, chemotherapy and targeted therapy (with particular attention to brain metastases from non-small cell lung cancer, melanoma and breast and renal cancer), and supportive care.

https://www.zora.uzh.ch/id/eprint/141068/1/Soffietti_2016.pdf

Diagnosis and treatment of brain metastases from solid tumors: guidelines from the European Association of Neuro-Oncology (EANO).

https://www.jto.org/article/S1556-0864(16)30466-X/pdf

EGFR TKIs plus WBRT Demonstrated No Survival Benefit Other Than That of TKIs Alone in Patients with NSCLC and EGFR Mutation and Brain Metastases

EGFR tyrosine kinase inhibitors versus cranial radiation therapy for EGFR mutant non-small cell lung cancer with brain metastases: A systematic review and meta-analysis

Radiotherapy (RT) primarily aims to locally destroy the tumor via the induction of DNA damage in the tumor cells. However, the so-called abscopal, namely systemic and immune-mediated, effects of RT move over more and more in the focus of scientists and clinicians since combinations of local irradiation with immune therapy have been demonstrated to induce anti-tumor immunity. We here summarize changes of the phenotype and microenvironment of tumor cells after exposure to irradiation, chemotherapeutic agents, and immune modulating agents rendering the tumor more immunogenic. The impact of therapy-modified tumor cells and damage-associated molecular patterns on local and systemic control of the primary tumor, recurrent tumors, and metastases will be outlined. Finally, clinical studies affirming the bench-side findings of interactions and synergies of radiation therapy and immunotherapy will be discussed. Focus is set on combination of radio(chemo)therapy (RCT) with immune checkpoint inhibitors, growth factor inhibitors, and chimeric antigen receptor T-cell therapy. Well-deliberated combination of RCT with selected immune therapies and growth factor inhibitors bear the great potential to further improve anti-cancer therapies.

/pdf/radio-immunotherapy-induced-immunogenic-cancer-cells-as-1791briqxo.pdf

Radio-Immunotherapy-Induced Immunogenic Cancer Cells as Basis for Induction of Systemic Anti-Tumor Immune Responses - Pre-Clinical Evidence and Ongoing Clinical Applications.

The aim of this paper is to explore the efficacy of whole brain radiotherapy (WBRT) versus WBRT concurrent with erlotinib in patients with multiple brain metastases of lung adenocarcinoma. WBRT was administered at 30Gy/10f in both arms. In the combination arm, 150 mg erlotinib was given each day, starting the first day of radiotherapy and continuing for 1 month following the end of radiotherapy. Thereafter, pemetrexed or docetaxel monotherapy or the best supportive therapy was given to both arms. The intracranial objective response rate and the local progression-free survival (LPFS) were primary endpoints. Toxicity, progression-free survival (PFS) and overall survival (OS) were secondary endpoints. Thirty-one patients in the WBRT group and 23 patients in the combination group were enrolled from November 2009 to December 2011. In the WBRT and the combination arms, respectively, the objective response rate was 54.84% and 95.65% (P = 0.001), the median local progression-free survival was 6.8 months and 10.6 months (P = 0.003), the median PFS was 5.2 months and 6.8 months (P = 0.009), and median OS was 8.9 months and 10.7 months (P = 0.020). In the combination group, there were no differences of LPFS, PFS, and OS between the epidermal growth factor receptor (EGFR) mutation patients and EGFR wild-type patients. No Grade 4 or higher side effects were observed in either group. A multivariate analysis indicated that erlotinib was the most important prognostic factor for a prolonged survival. Data showed that erlotinib in combination with WBRT had a tolerable toxicity profile and prolonged the LPFS, PFS, and OS of lung adenocarcinoma patients with multiple brain metastases compared with WBRT monotherapy.

/pdf/phase-ii-study-of-whole-brain-radiotherapy-with-or-without-4b2g8auwh2.pdf

Phase II study of whole brain radiotherapy with or without erlotinib in patients with multiple brain metastases from lung adenocarcinoma.

The combination of radiotherapy and targeted therapy is an important approach in the application of targeted therapy in clinical practice, and represents an important opportunity for the development of radiotherapy itself. Numerous agents, including epidermal growth factor receptor, monoclonal antibodies, tyrosine kinase inhibitors, and antiangiogenic therapies, have been used for targeted therapy. A number of studies of radiotherapy combined with targeted therapy in non-small-cell lung carcinoma have been completed or are ongoing. This paper briefly summarizes the drugs involved and the important related clinical research, and indicates that considerable progress has been made with the joint efforts of the two disciplines. Many issues, including drug selection, identification of populations most likely to benefit, timing of administration of medication, and side effects of treatment require further investigation. However, further fundamental research and accumulation of clinical data will provide a more comprehensive understanding of these therapies. Targeted therapy in combination with radiotherapy has a bright future.

/pdf/progress-of-clinical-research-on-targeted-therapy-combined-4wd2oulmh9.pdf

Progress of clinical research on targeted therapy combined with thoracic radiotherapy for non-small-cell lung cancer

Background and objective The clinical value of postoperative radiotherapy (PORT) in stage N2 nonsmall-cell lung cancer (NSCLC) is controversy. The aim of this study is to analyze the efficacy of PORT in subgroup of stage N2 NSCLC, which can help clinicians to choose proper patients for PORT. Methods Clinical data of 359 patients with stage N2 NSCLC treated with radical surgery between Mar. 2000 and Jul. 2005 were retrospectively reviewed. Two hundred and seven patients received adjuvant chemotherapy and one hundred and four patients received adjuvant radiotherapy. First, the group of patients were analyzed to evaluate the factors affecting the overall survival. The all patients were divided based on tumor size and the number of lymph node metastasis station (single station or multiple station) so as to evaluate the role of PORT. The endpoint was overall survival (OS) and local recurrence-free survival (LRFS). Kaplan-Meier method was used to calculate the OS, LRFS and Log-rank was used to compare the difference in OS and LRFS between different groups. Results The median duration of follow-up was 2.3 years. 224 patients died. The median survival was 1.5 years and 1, 3, 5-year survival were 78%, 38% and 26%. Univariate analysis showed tumor size, the number of lymph node metastasis station and PORT were correlated with OS. Among patients, 5-year survival rates in PORT and non-PORT were 29% and 24% (P=0.047) respectively. In subgroups, PORT was related with high survival in patients with multiple station N2 compared to non-PORT: 36% vs 20% (P=0.013) and 33% vs 15% (P=0.002) in patients in patients with tumor size > 3 cm. Also, it was related with low local recurrence compared to non-PORT: 65% vs 48% (P=0.006) and 62% vs 48% (P=0.033). Conclusion PORT can improve overall survival for N2 NSCLC, especially the patients with the factors as follows: tumor size > 3 cm and multiple station N2 can benefit from PORT more or less.

[The Role of Postoperative Radiotherapy on Stage N2 Non-small Cell Lung Cancer.].

Background and objective Postoperative radiotherapy (PORT) after complete resection of non-small cell lung cancer (NSCLC) has been introduced in order to reduce locoregional recurrence, but it remains controversy whether PORT can improve survival. Therefore, we want to investigate the effect of PORT and the relationship between failure patterns and primarily location of stage IIIA (N2) in NSCLC. Methods This retrospective analysis included 233 patients who underwent resection of NSCLC, first recurrence involving a local-regional site. It illustrated the factors affecting local recurrence and the sites of failure on the basis of lobe of primary tumor. Results Multivariable analysis demonstrated the number of positive lymph nodes (P=0.003), T stage (P < 0.001), histological type (P=0.038), modus operandi (P=0.013) and the number of mediastinal lymph node stations involved (P=0.018) were the independent factors. For all patients, the most common site of failure was the bronchial stump/staple line, which was present more often in those who had a wedge resection than in those who had a more radical procedure (P < 0.001). The local-region frequency of squamous was higher than adenocarcinoma carcinoma (P=0.025). The recurrence frequency of mediastinal lymph node among T1 and T2-3 were 36.4%, 62.0% (P=0.009) respectively. The localregion recurrence among primarily tumor location were different. Conclusion The number of positive lymph nodes, T stage, histological type, modus operations and the number of mediastinal lymph node stations involved were the independent factors in IIIA (N2) NSCLC.

Ping Wang

Papers

Phase II study of whole brain radiotherapy with or without erlotinib in patients with multiple brain metastases from lung adenocarcinoma.

Progress of clinical research on targeted therapy combined with thoracic radiotherapy for non-small-cell lung cancer

[The Role of Postoperative Radiotherapy on Stage N2 Non-small Cell Lung Cancer.].

Research on postoperative radiotherapy for non-small cell lung cancer of stage IIIA (N2) according to the failure patterns after pulmonary resection