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Purpose: The phase II prospective, noncomparative BRAIN study (NCT00800202) investigated efficacy and safety of bevacizumab in chemotherapy-na€ ve or pretreated patients with nonsmall cell lung cancer (NSCLC) and asymptomatic untreated brain metastases to provide data in this previously unexplored subgroup.Experimental Design: Patients with stage IV nonsquamous NSCLC, Eastern Cooperative Oncology Group performance status 0-1, and untreated, asymptomatic brain metastases received first-line bevacizumab (15 mg/kg) plus carboplatin (area under the curve Â6) and paclitaxel (200 mg/m 2 ) every 3 weeks (B þ CP), or second-line bevacizumab plus erlotinib (150 mg/d; B þ E). Six-month progression-free survival (PFS) was the primary endpoint. The trial could be stopped if there were more than three (B þ CP) or more than two (B þ E) intracranial hemorrhages.Results: In first-line B þ CP cohort (n ¼ 67), 6-month PFS rate was 56.5% with a median PFS of 6.7 months [95% confidence interval (CI), 5.7-7.1] and median overall survival (OS) of 16.0 months. Investigator-assessed overall response rate (ORR) was 62.7%: 61.2% in intracranial lesions and 64.2% in extracranial lesions. Because of low enrolment (n ¼ 24), efficacy results for the second-line B þ E cohort were exploratory only; 6-month PFS rate was 57.2%, median PFS was 6.3 months (95% CI, 3.0-8.4), median OS was 12.0 months, and ORR was 12.5%. Adverse events were comparable with previous trials of bevacizumab. One grade 1 intracranial hemorrhage occurred and resolved without sequelae.Conclusions: The BRAIN study demonstrates encouraging efficacy and acceptable safety of bevacizumab with first-line paclitaxel and carboplatin in patients with NSCLC and asymptomatic, untreated brain metastases.

Patients with advanced thymic malignancies may receive multiple lines of systemic therapy, with an opportunity for clinically relevant PFS rates for which objective response may be a surrogate. Our real-life study provides landmark efficacy data that are needed when designing clinical trials to assess innovative agents.

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BackgroundThe use of antibiotics (ATB) and proton-pump inhibitors (PPI) alters the composition and diversity of the gut microbiota, which can influence the immune system, consequently interfering with response to anti-PD1 immune checkpoint inhibitors (ICI). We assessed the impact of ATB and/or PPI use on the efficacy and safety of ICI.MethodsTwo hundred twelve patients treated with anti-PD1 ICI for non-small cell lung carcinoma, melanoma, upper airway & digestive tract carcinoma or renal cell carcinoma were retrospectively included. Patients having received ATB within 60 days before ICI initiation were included in the ATB+ group. Patients having received PPI within 30 days before ICI initiation were included in the PPI+ group. Four groups were thus considered: ATB-/PPI-, ATB+/PPI-, ATB-/PPI+, ATB+/PPI+. Response rate was assessed by RECIST v1.1. Overall survival (OS), progression-free survival (PFS) and adverse events, recorded using Common Terminology Criteria for Adverse Events Version 5, were compared using inverse probability of treatment weighting to account for selection bias.ResultsPFS at 6 months was 56.7 %, 95%CI (49.6%; 63.2%) and 47.2 %, 95%CI (39.8%;54.1%) at 12 months. OS was 81.6%, 95%CI (75.6%; 86.2%) at 6 months, and 69.4%, 95%CI (61.9%;75.7%) at 12 months. Compared to ATB-/PPI- group, PFS was lower for the ATB+/PPI- group [Hazard ratio (HR) 1.90, 95%CI (1.41;2.57)] and the ATB-/PPI+ group [HR 1.51, 95%CI (1.11;2.05)], and lowest in the ATB+/PPI+ group [HR 3.65, 95%CI (2.75;4.84)]. For OS, the use of ATB alone or PPI alone or in combination was a risk factor for death, with each increasing HR values by a similar magnitude, and the combination of ATB and PPI did not increase risk further. AEs were observed in 78 cases (36.8%) with no significant impact of ATB or PPI use.ConclusionsThis study reveals that ATB and/or PPI use can alter response to anti-PD1 ICI, and the prognosis of cancer patients. The microbiota mechanisms involved in the response to ICI should be investigated to optimize patient management.

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Background. Because most cases of non-small cell lung cancer (NSCLC) are diagnosed at an advanced stage with a poor prognosis, patient inclusion in clinical trials is critical. Most trials require an estimated life expectancy >3 months, based on clinician estimates of patient survival probability, without providing formal guidelines. The aim of this study was to assess the accuracy of clinicians' predictions of survival in NSCLC patients (stages IIIB, and IV) and the possible impact of patient quality of life on survival estimation.Methods. At diagnosis, clinical, biological, and quality of life data (QLQ-C30 questionnaire) were recorded, and doctors "forecast" each patient's estimated survival. Concordance between predicted and actual survival was assessed with the intraclass correlation coefficient.Results. Eighty-five patients with a mean age of 62.2 years, 81.1% male, were included (squamous cell carci-

Endobronchial ultrasound-guided transbronchial needle aspiration has demonstrated its accuracy in the diagnostic workup of enlarged mediastinal lymph nodes. In addition to conventional smears, the use of liquid-based cytology (LBC) and cell block preparations (CBP) has been introduced more recently. The aim of our study was to determine the performance of each of the different techniques, separately and combined, in terms of diagnostic yield and sensitivity. A total of 290 consecutive patients were included. The pathological examination was based on smear cytology, LBC, and CBP. Adequate sampling was defined by the presence of pathological material or lymphocytes. The global diagnostic yield was 82.7 % and the sensitivity was 89.1 %. The diagnostic yield was 72.8 % for smears, 78.8 % for LBC, and 69.9 % for CBP. The combination of smears with CBP significantly increased diagnostic yield (p = 0.01) and sensitivity (p = 0.006), but not the combination of smears with LBC (yield: p = 0.07; sensitivity: p = 0.13). The combination of the three techniques further increased yield (p = 0.007) and sensitivity (p = 0.006), compared with smears alone. CBP were more sensitive than smears for both diagnoses of carcinoma (p = 0.01) and granulomatous inflammation (p = 0.048). Conversely, LBC was less sensitive than smears for granulomatous inflammation (p = 0.004), but the difference was not significant for carcinoma (p = 0.42). CBP, as a complement to smears, increases diagnostic yield and sensitivity for both diagnoses of carcinoma and granulomatous inflammation. LBC, if used alone, increases the risk of a false-negative result.