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Acquired resistance (AR) to programmed cell death protein 1/programmed death-ligand 1 [PD-(L)1] blockade is frequent in non-small-cell lung cancer (NSCLC), occurring in a majority of initial responders. Patients with AR may have unique properties of persistent antitumor immunity that could be re-harnessed by investigational immunotherapies. The absence of a consistent clinical definition of AR to PD-(L)1 blockade and lack of uniform criteria for ensuing enrollment in clinical trials remains a major barrier to progress; such clinical definitions have advanced biologic and therapeutic discovery. We examine the considerations and potential controversies in developing a patient-level definition of AR in NSCLC treated with PD-(L)1 blockade. Taking into account the specifics of NSCLC biology and corresponding treatment strategies, we propose a practical, clinical definition of AR to PD-(L)1 blockade for use in clinical reports and prospective clinical trials. Patients should meet the following criteria: received treatment that includes PD-(L)1 blockade; experienced objective response on PD-(L)1 blockade (inclusion of a subset of stable disease will require future investigation); have progressive disease occurring within 6 months of last anti-PD-(L)1 antibody treatment or rechallenge with anti-PD-(L)1 antibody in patients not exposed to anti-PD-(L)1 in 6 months. • In NSCLC, acquired resistance to immunotherapy is common and poorly understood. • A uniform clinical definition is imperative to further characterize patients and develop a rational approach to overcoming acquired resistance. • The proposed definition seeks to unify language for future reports and clinical trials in NSCLC. • We also highlight specific areas of uncertainty in classification of acquired resistance that require urgent attention and could lead to further refinements in the future. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Percutaneous transthoracic needle biopsy is a useful and common procedure in the investigation of a lung nodule. The occurrence of air embolism after percutaneous transthoracic needle biopsy is extremely rare. Case report: We report a 62-year-old woman who presented with neurological signs including restlessness, meningeal signs and focal neurologic deficits 4hours after percutaneous transthoracic lung biopsy, related to air embolism. The outcome was favorable with hyperbaric oxygen therapy. Conclusion: Percutaneous transthoracic needle biopsy complicated by air embolism has been rarely reported. It usually occurs within minutes after the biopsy. The late onset of this adverse event in our patient is exceptional. Air embolism occurs more frequently after biopsy of lung infiltrates compared to nodules. Occurrence of a pneumothorax or an intraalveolar haemorrhage following a percutaneous transthoracic needle biopsy may be warning manifestations and justify a close monitoring. [Copyright &y& Elsevier]

Abstract: The aim of this study was to determine the impact of patient selection based on age, comorbidity and performance status on the efficacy of platinum-free combination therapy on non-small-cell lung cancer after 65 years of age. We analyzed the overall response rate, the median survival time, the 1-year survival rate, toxicity and quality of life after one to three 6-week cycles of docetaxel 30mg/m2 weekly and gemcitabine 900mg/m2 at weeks 1, 2, 4 and 5. Fifty patients (median age 73.7 years) were eligible. The mean number of comorbid conditions per patient was 0.8 [Balducci L. Lung cancer and aging. ASCO 2005. Educational book. p. 587–91; Piquet J, Blanchon F, Grivaux M, et al. Primary bronchial carcinoma in elderly subjects in France. Rev Mal Respir 2003;20:691–9; Jatoi A, Hillman S, Stella P, et al. Should elderly non-small-cell lung cancer patients be offered elderly-specific trials? Results of a pooled analysis from the North Central Cancer Treatment Group. J Clin Oncol 2005;23:9113–9; Balducci L, Extermann M. Management of cancer in the older person: a practical approach. Oncologist 2000;5:224–37]. Forty-five patients were assessable: 17 (34%) had an objective response, 18 (36%) had stable disease and 10 progressed (20%). The median survival time was 7 months and the 1-year survival rate 23.5%. The main grade III–IV adverse event was neutropenia (32% of patients). Conclusion: Platinum-free dual-agent chemotherapy gives similar results in patients over 65, selected on the basis of their precise age and comorbidity, to that reported in younger subjects. [Copyright &y& Elsevier]

Summary: Purpose: To evaluate the efficacy and safety of gemcitabine and carboplatin in the treatment of previously untreated patients with advanced non-small cell lung cancer (NSCLC). Methods: A randomized phase II study was conducted by the Groupe Français de Pneumo-Cancérologie (GFPC) in 15 centers. The patients were randomized in either arm A (GC): gemcitabine 1250mg/m2 on days 1 and 8+carboplatin AUC 6mg/(mLmin) on day 1; or in arm B (VP): vinorelbine 30mg/m2 weekly+cisplatin 80mg/m2 on day 1. Treatment cycles were repeated every 3 weeks. Results: A total of 100 patients were randomized with stage IV or stage III NSCLC with malignant pleural effusion: 51 patients in arm A and 49 patients in arm B. A total of 190 cycles were administered in the GC arm and 172 cycles in the VP arm, with a median of four cycles per patient in each arm. The dose intensity was 84.9% for gemcitabine, 99.8% for carboplatin, 97.7% for cisplatin and 67.7% for vinorelbine. The objective response rates were 19.6% (95% CI, 9.8–33.1) for GC and 29.2% (95% CI, 17.0–44.1) for VP in an ITT analysis. The response duration was 169 days in arm A and 226 days in arm B. The TTP was similar with 140 days (GC) and 148 days (VP), respectively. Overall survival rates were 334 days in the GC combination and 304 days in the VP combination. Overall, the treatment was safe and toxicities observed were different in each arm: neutropenia was the most common toxicity in the VP treatment, whereas thrombocytopenia was more frequent in the GC combination. Anemia was similar in both arms. Non-haematologic toxicity was mild. One toxic death in arm A and three toxic deaths in arm B were observed. Conclusion: In terms of response rate, the gemcitabine–carboplatin combination was not efficient enough to allow further phase III study. Survival data are in the same range as the standard arm. This chemotherapy is feasible and may represent an alternative to a standard cisplatin-based regimen, allowing treatment in an outpatient setting. [Copyright &y& Elsevier]