Efficacy of chemotherapy and atezolizumab in patients with non-small-cell lung cancer receiving antibiotics and proton pump inhibitors: pooled post hoc analyses of the OAK and POPLAR trials.

BACKGROUND: Preclinical data have shown that proton pump inhibitors (PPI) can modulate the microbiome, and single-arm studies suggested that antibiotics (ATB) may decrease the efficacy of immune checkpoint inhibitors (ICI), but randomized controlled trial data are lacking. This pooled analysis evaluated the effect of ATB and PPI on outcome in patients randomized between ICI and chemotherapy. PATIENTS AND METHODS: This retrospective analysis used pooled data from the phase II POPLAR (NCT01903993) and phase III OAK (NCT02008227) trials, which included 1512 patients with previously treated non-small-cell lung cancer (NSCLC) randomly assigned to receive atezolizumab (n = 757) or docetaxel (n = 755). The main objective of this analysis was to assess the impact of ATB and PPI use on overall survival (OS) and progression-free survival (PFS). RESULTS: A total of 169 (22.3%) patients in the atezolizumab group and 202 (26.8%) in the docetaxel group received ATB, and 234 (30.9%) and 260 (34.4%), respectively, received PPI. Multivariate analysis in all patients revealed that ATB were associated with shorter OS [hazard ratio (HR) 1.20, 95% confidence interval (CI) 1.04-1.39], as was PPI (HR 1.26, 95% CI 1.10-1.44). Within the atezolizumab population, OS was significantly shorter in patients who received ATB (8.5 versus 14.1 months, HR 1.32, 95% CI 1.06-1.63, P = 0.01) or PPI (9.6 versus 14.5 months, HR 1.45, 95% CI 1.20-1.75, P = 0.0001). PPI use was associated with shorter PFS in the atezolizumab population (1.9 versus 2.8 months, HR 1.30, 95% CI 1.10-1.53, P = 0.001). There was no association between ATB and PPI use and PFS or OS within the docetaxel population. CONCLUSION: In this unplanned analysis from two randomized trials, data suggest that ATB or PPI use in patients with metastatic NSCLC is associated with poor outcome and may influence the efficacy of ICI.

(18F)-FDG PET/CT parameters to predict survival and recurrence in patients with locally advanced cervical cancer treated with chemoradiotherapy.

PURPOSE: To identify predictive (18F)-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT)-based parameters for locoregional control, disease-free survival and overall survival, by testing different thresholds of metabolic tumor volume and total lesion glycolysis in patients with locally-advanced cervical cancer. PATIENTS AND METHODS: Thirty-seven patients treated with standard chemoirradiation underwent a pretreatment (18F)-FDG-PET/CT. Using different thresholds of maximum standardized uptake value, the following PET parameters were computed: maximum standardized uptake value, mean standardized uptake value, metabolic tumor volume and total lesion glycolysis for primary tumor and lymph nodes and a new parameter combining the metabolic tumor volume and the distance between lymph nodes and the primary tumor, namely metabolic node distance. Correlation between PET and clinical parameters with clinical outcome (overall survival, disease-free survival, and locoregional control) was assessed using univariate and multivariate analyses (Cox model). RESULTS: In univariate analyses, PET/CT parameters associated with overall survival and disease-free survival were: metabolic tumor volume and total lesion glycolysis of the primary tumor, total lesion glycolysis of lymph nodes and metabolic node distance. The most predictive threshold segmentation for metabolic tumor volume and total lesion glycolysis was 48% of maximum standardized uptake value for the primary tumor and 30% for the lymph nodes. In multivariate Cox analysis, the total lesion glycolysis of primary tumor 48% and metabolic node distance were the two independent risk factors for overall survival (P<0.01), disease-free survival (P<0.01) and locoregional control (P=0.046). CONCLUSION: Total lesion glycolysis of primary tumor and distance between the invaded positive lymph node and the primary tumor seem to have the highest predictive value when compared to classical clinical prognostic parameters and may be useful to identify high risk groups at time of diagnosis and to tailor the therapeutic approach in locally-advanced cervical cancer.

Systemic review: Radiation therapy alone in medical non-operable endometrial carcinoma.

BACKGROUND AND PURPOSE: Radiotherapy is a good option for inoperable and frail patients diagnosed with endometrial cancer. Because of the lack of large multicentre trials, a systematic review was performed in an attempt to get an overview on the feasibility and efficacy of this specific approach. MATERIALS AND METHODS: We performed a bibliographic search for articles in English or French which were published in PubMed from the start of this database in January 1969 to identify publications on radiation therapy (RT) as single treatment for localised non-operable carcinoma of the endometrium. The review was completed following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. RESULTS: Twenty-five reports containing 2694 patients treated with RT as single treatment were identified that fulfilled the selection criteria. Disease-specific survival (DSS) at 5 years was reported for a cohort of 1322 (49.1%) patients. The combined DSS for this group of patients was 78.5% (range: 68.4-92%; 95% confidence interval: 74.5-82.5). External beam radiation therapy (EBRT) combined with brachytherapy (BT) was used in 1278 patients (47.4%), BT alone in 1383 patients (51.3%), and EBRT alone in 33 patients (1.2%). The average occurrence of grade III or worse late toxicity was 3.7% for EBRT + BT, 2.8% for BT alone, and 1.2% for EBRT alone. CONCLUSIONS: RT is in terms of disease control and toxicity, an acceptable option for non-surgical candidate patients. Prospective multicentre randomised or observational trials are needed to validate these results.

Molecular targeted agents combined with chemo-radiation in the treatment of locally advanced cervix cancer.

Despite improvements in survival after the introduction of chemo-radiotherapy (CRT) in the treatment of patients with cervical cancer, loco-regional control of this disease continues to be a major problem. The present article reviews current and emerging therapeutic strategies combining CRT with novel molecular agents that specifically target the abnormal tumor microenvironment, with the aim of improving local control and survival in patients with locally advanced cervix cancer. The evidence supporting the biological rational to combine novel non-cytotoxic agents with CRT is strong, and drugs targeting different molecular pathways are currently under clinical development (EGFR inhibitors, COX-2 inhibitors, hypoxia targeted agents, etc). Early pre-clinical and clinical strategies also favor the use of vascular-targeted agents with the aim to normalize the abnormal tumor vasculature, increase tumor oxygenation, and reduce interstitial fluid pressure (IFP). The integration of these novel targeted therapies with CRT in clinical trials is discussed, as well as new and promising biomarkers to test drug activity.

Cáncer de mama metastásico en ojo y órbita: tratamiento radiante. Nuestra experiencia / Breast carcinoma metastatic to the eye and orbit: our experience

Los tumores malignos más frecuentes en ojo y órbita son las metástasis. El cáncer de mama es el tumor que con más frecuencia metastatiza en ojo y órbita (40 por ciento-50 por ciento de los casos según las distintas series). El tratamiento tiene como uno de sus pilares a la radioterapia. Objetivos: evaluar la eficacia del tratamiento radiante en pacientes (ptes.) con cáncer de mama metastásico en ojo y órbita. Materiales y métodos: entre los años 1996-2002 recibieron tratamiento radiante 17 ptes. con tumores metastásicos en ojo y órbita, de ellos 9 ptes. (53 por ciento) tenían metástasis óculo-orbitarias de cáncer de mama. La edad media fue 54 años (R: 43-84 años). Todas las ptes. son de sexo femenino. La localización de las metástasis fue: ojo derecho, 2 ptes.; ojo izquierdo, 5 ptes.; compromiso orbitario bilateral, 2 ptes. De las 9 ptes., 3 presentaron metástasis en coroides y 6 en órbita...