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Introduction: For patients with locally advanced pancreatic cancer (LAPC), who are candidates for radiation therapy, dose-escalated radiation therapy (RT) offers unique benefits over traditional radiation techniques. In this review, we present a historical perspective of dose-escalated RT for LAPC. We also outline advances in SBRT delivery, one form of dose escalation and a framework for selecting patients for treatment with SBRT. Results: Techniques for delivering SBRT to patients with LAPC have evolved considerably, now allowing for dose-escalation and superior respiratory motion management. At the same time, advancements in systemic therapy, particularly the use of induction multiagent chemotherapy, have called into question which patients would benefit most from radiation therapy. Multidisciplinary assessment of patients with LAPC is critical to guide management and select patients for local therapy. Results from ongoing trials will establish if there is a role of dose-escalated SBRT after induction chemotherapy for carefully selected patients. Conclusion: Patients with LAPC have more therapeutic options than ever before. Careful selection for SBRT may enhance patient outcomes, pending the maturation of pivotal clinical trials.
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Background: The administration of immune checkpoint inhibitors (ICIs) in advanced non-small cell lung cancer (NSCLC) with oncogenic driver alterations other than epidermal growth factor receptor (EGFR) aroused a heated discussion. We thus aimed to evaluate ICI treatment in these patients in real-world routine clinical practice. Methods: A multicenter, retrospective study was conducted for NSCLC patients with at least one gene alteration (KRAS, HER2, BRAF, MET, RET, ALK, ROS1) receiving ICI monotherapy or combination treatment. The data regarding clinicopathologic characteristics, clinical efficacy, and safety were investigated. Results: A total of 216 patients were included, the median age was 60 years, 72.7% of patients were male, and 46.8% had a smoking history. The molecular alterations involved KRAS (n=95), HER2 (n=42), BRAF (n=22), MET (n=21), RET (n=14), ALK (n=14), and ROS1 (n=8); 56.5% of patients received immunotherapy in the first-line, and the rest 43.5% were treated as a second-line and above. For the entire cohort who received immunotherapy-based regimens in the first-line, the median progression-free survival (PFS) was 7.5 months and the median overall survival (OS) was 24.8 months. For the entire cohort who received immunotherapy-based regimens in the second-line and above, the median PFS was 4.7 months and median OS was 17.1 months. KRAS mutated NSCLC treated with immunotherapy-based regimens in the first-line setting had a median PFS and OS were 7.8 and 26.1 months, respectively. Moreover, the median PFS and OS of immunotherapy-based regimens for KRAS-mutant NSCLC that progressed after chemotherapy were 5.9 and 17.1 months. Programmed death ligand 1 (PD-L1) expression level was not consistently associated with response to immunotherapy across different gene alteration subsets. In the KRAS group, PD-L1 positivity [tumor proportion score (TPS) ≥1%] was associated with better PFS and OS according to the multivariate Cox analysis. No statistically significant association was found for smoking status, age, or gender with clinical efficacy in any gene group analyses. Conclusions: KRAS-mutant NSCLC could obtain clinical benefits from ICIs either for treatment-naive patients or those who have experienced progression after chemotherapy, and PD-L1 positive expression (TPS >1%) may be a potential positive predictor. For NSCLC with ALK, RET and ROS1 rearrangement, MET exon 14 skipping mutation, or BRAF V600E mutation, effectiveness of single or combined ICI therapy remains limited, therefore, targeted therapies should be considered prior to immunotherapy regimens. Future studies should address the investigation of better predictive biomarkers for immunotherapy response in oncogene-driven NSCLC.
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Late diagnosis of human immunodeficiency virus (HIV) is associated with early progression to acquired immunodeficiency syndrome (AIDS). We examined racial/ethnic differences in presentation with advanced HIV/AIDS at a community health center in New Jersey. Records of patients diagnosed with HIV between 1990 and 2018 were reviewed. Odds ratios (OR) of presenting with AIDS at HIV diagnosis were computed in unadjusted and adjusted models. There were 182 (48.3%) Latino, 48 (12.7%) non-Latino White (NLW), 130 (34.5%) non-Latino Black, and 17 (4.5%) non-Latino of other race/ethnicity included in the analysis. Over 75% of the Latinos were foreign-born. Latino patients had higher odds of presentation with AIDS at time of HIV diagnosis than NLW in unadjusted (OR = 4.85, 95% confidence interval (95% CI): 2.28-10.31) and adjusted models (OR = 3.71, 95%CI: 1.60-8.59). Latino patients, particularly foreign-born and bisexual, had higher odds of being diagnosed with AIDS at presentation with HIV in this cohort.