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Introduction and background: While recurrent glioblastoma patients are often treated with re-irradiation, there is limited data on the use of re-irradiation in the setting of bevacizumab (BEV), temozolomide (TMZ) re-challenge, or immune checkpoint inhibition (ICI). We describe target delineation in patients with prior anti-angiogenic therapy, assess safety and efficacy of re-irradiation, and evaluate patterns of recurrence. Materials and methods: Patients with a histologically confirmed diagnosis of glioblastoma treated at a single institution between 2013 and 2021 with re-irradiation were included. Tumor, treatment and clinical data were collected. Logistic and Cox regression analysis were used for statistical analysis. Results: One hundred and seventeen recurrent glioblastoma patients were identified, receiving 129 courses of re-irradiation. In 66 % (85/129) of cases, patients had prior BEV. In the 80 patients (62 %) with available re-irradiation plans, 20 (25 %) had all T2/FLAIR abnormality included in the gross tumor volume (GTV). Median overall survival (OS) for the cohort was 7.3 months, and median progression-free survival (PFS) was 3.6 months. Acute CTCAE grade ≥ 3 toxicity occurred in 8 % of cases. Concurrent use of TMZ or ICI was not associated with improved OS nor PFS. On multivariable analysis, higher KPS was significantly associated with longer OS (p

Introduction and Background: While recurrent glioblastoma patients are often treated with re-irradiation, there is limited data on the use of re-irradiation in the setting of bevacizumab (BEV), temozolomide (TMZ) re-challenge, or immune checkpoint inhibition (ICI). We describe target delineation in patients with prior anti-angiogenic therapy, assess safety and efficacy of re-irradiation, and evaluate patterns of recurrence., Materials and Methods: Patients with a histologically confirmed diagnosis of glioblastoma treated at a single institution between 2013 and 2021 with re-irradiation were included. Tumor, treatment and clinical data were collected. Logistic and Cox regression analysis were used for statistical analysis., Results: One hundred and seventeen recurrent glioblastoma patients were identified, receiving 129 courses of re-irradiation. In 66 % (85/129) of cases, patients had prior BEV. In the 80 patients (62 %) with available re-irradiation plans, 20 (25 %) had all T2/FLAIR abnormality included in the gross tumor volume (GTV). Median overall survival (OS) for the cohort was 7.3 months, and median progression-free survival (PFS) was 3.6 months. Acute CTCAE grade ≥ 3 toxicity occurred in 8 % of cases. Concurrent use of TMZ or ICI was not associated with improved OS nor PFS. On multivariable analysis, higher KPS was significantly associated with longer OS (p < 0.01). On subgroup analysis, patients with prior BEV had significantly more marginal recurrences than those without (26 % vs. 13 %, p < 0.01)., Conclusion: Re-irradiation can be safely employed in recurrent glioblastoma patients. Marginal recurrence was more frequent in patients with prior BEV, suggesting a need to consider more inclusive treatment volumes incorporating T2/FLAIR abnormality., Competing Interests: CH has received research support through the “Filling the Gap” Program of the University of Zurich. CH has received honoraria from Vifor. DAR has received research support through DFCI from Acerta Phamaceuticals; Agenus; Bristol-Myers Squibb; Celldex; EMD Serono; Enterome; Epitopoietic Research Corporation; Incyte; Inovio; Insightec; Merck; Novartis; Omniox; Tragara. DAR has received advisory fees from Agios; AnHeart Therapeutics; Avita Biomedical, Inc., Bristol Myers Squibb; Boston Biomedical; CureVac AG; Del Mar Pharma; DNAtrix; Hoffman-LaRoche, Ltd; Imvax; Janssen; Kiyatec; Medicenna Therapeutics; Neuvogen; Novartis; Novocure; Pyramid; Sumitomo Dainippon Pharma; Vivacitas Oncology, Inc Y-mabs Therapeutics. DAR has received Honoraria from Abbvie; Advantagene; Agenus; Agios; Amgen; Avita Biomedical, Inc., Bayer; Boston Biomedical; Boehringer Ingelheim; Bristol-Myers Squibb; Celldex; Deciphera; DelMar; Ellipses Pharma; EMD Serono; Genenta; Genentech/Roche; Imvax; Inovio; Kintara; Kiyatec; Medicenna Biopharma, Inc.; Merck; Merck KGaA; Monteris; Neuvogen; Novartis; Novocure; Oncorus; Oxigene; Regeneron; Stemline; Sumitono Dainippon Pharma; Taiho Oncology, Inc. NA reports personal fees from AstraZeneca; Debiopharm; ViewRay; BrainLab. NA received research grants from ViewRay. MG has received research support from ViewRay; AstraZeneca. MG is the current President-elect of ESTRO. MW has received research grants from Versameb; Quercis. MW has received consulting fees from Bayer; Curevac; Medac; Novocure; Philogen; Roche; Sandoz. MW has received honoraria from Novartis. MV holds a board role at Orbus. PY has received research grants from Astra Zeneca/Medimmune; Black Diamond; Beigene; Celgene; Chimerix; Eli Lily; Erasca; Genentech/Roche; Kazia; MediciNova; Merck; Novartis; Nuvation Bio; Puma, Servier; Vascular Biogenics; VBI Vaccines. PY has received consulting fees from Astra Zeneca, Bayer; Black Diamond; Boehringer Ingelheim; Boston Pharmaceuticals; Celularity; Chimerix; Day One Bio; Genenta; Glaxo Smith Kline; Karyopharm; Merck, Mundipharma; Novartis; Novocure; Nuvation Bio; Prelude Therapeutics; Sapience; Servier; Sagimet; Vascular Biogenics; VBI Vaccines. PY holds board positions at Novocure; Day One Bio.The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Abstract: The standard palliative treatment for advanced stage NSCLC remains a platinum doublet but by tailoring chemotherapy according to tumour histology the results can be improved through using pemetrexed-containing schemas in non-squamous-cell disease. In addition, maintenance chemotherapy appears to be effective in patients achieving clinical benefit by induction therapy. Targeted therapy based on the presence of activating epidermal growth factor receptor (EGFR) activating mutations or EML4–ALK gene rearrangement is becoming standard practice with high median survival rates, up to 30months. There are still numerous other molecular targeted drugs in development. This review presents the most recent relevant progress in systemic anti-cancer therapy of advanced NSCLC in the past 5years and delineates today’s new treatment options. [Copyright &y& Elsevier]