Purpose Identification of predictive biomarkers is critically needed to improve selection of patients who derive the most benefit from platinum-based chemotherapy. We hypothesized that decreased expression of SMARCA4/BRG1, a known regulator of transcription and DNA repair, is a novel predictive biomarker of increased sensitivity to adjuvant platinum-based therapies in NSCLC. Experimental Design The prognostic value was tested using a gene expression microarray from the Director’s Challenge Lung Study (n=440). The predictive significance of SMARCA4 was determined using a gene expression microarray (n=133) from control and treatment arms of the JBR.10 trial of adjuvant cisplatin/vinorelbine. Kaplan-Meier method and log-rank tests were used to estimate and test the differences of probabilities in overall survival (OS) and disease-specific survival (DSS) between expression groups and treatment arms. Multivariate Cox regression models were used while adjusting for other clinical covariates. Results In the Director’s Challenge Study, reduced expression of SMARCA4 was associated with poor OS compared to high and intermediate expression (P<0.001 and P=0.009, respectively). In multivariate analysis, compared to low, high SMARCA4 expression predicted a decrease in risk of death (HR=0.6, 95% CI: 0.4–0.8, P=0.002). In the JBR.10 trial, improved five-year DSS was noted only in patients with low SMARCA4 expression when treated with adjuvant cisplatin/vinorelbine (HR=0.1, 95% CI: 0.0–0.5, P=0.002 [low]; HR 1.0, 95% CI: 0.5–2.3, P=0.92 [high]). An interaction test was highly significant (P=0.01). Conclusions Low expression of SMARCA4/BRG1 is significantly associated with worse prognosis; however, it is a novel significant predictive biomarker for increased sensitivity to platinum-based chemotherapy in NSCLC.

for the German Rectal Cancer Study Group IMPORTANCE Total neoadjuvant therapy has been increasingly adopted for multimodal rectal cancer treatment. The optimal sequence of chemoradiotherapy (CRT) and chemotherapy needs to be established. OBJECTIVE To report the long-term results of the secondary end points prespecified in the Randomized Phase 2 Trial of Chemoradiotherapy Plus Induction or Consolidation Chemotherapy as Total Neoadjuvant Therapy (CAO/ARO/AIO-12 trial) for Locally Advanced Rectal Cancer. DESIGN, SETTING, AND PARTICIPANTS This secondary analysis of a randomized clinical trial included 311 patients who were recruited from the accrued CAO/ARO/AIO-12 trial population

Ga-PSMA PET/CT and mpMRI provided concordant results for delineation of the DIPL in 47 % of patients (40 % - 54 % of lesions). GTV-PET was significantly larger than GTV-MRIint. (68)Ga-PSMA PET/CT may have a role in radiation treatment planning for focal radiation to the DIPL. Exact correlation of PET and MRI images with histopathology is needed.