Risk Stratification of Locally Advanced Non-Small Cell Lung Cancer (NSCLC) Patients Treated with Chemo-Radiotherapy: An Institutional Analysis.

BACKGROUND: The purpose of this study was to determine which factors predicted survival and to derive a risk prediction model for patients with locally advanced non-small cell lung cancer (NSCLC) receiving concurrent chemo-radiotherapy (cCRT). METHODS: This investigation included 149 patients with locally advanced NSCLC who were treated with cCRT at Stony Brook University Hospital between 2007 and 2015. A finite set of demographic, clinical, and treatment variables were evaluated as independent prognostic factors. Kaplan-Meier survival curves were generated, and log rank tests were used to evaluate difference in survival between groups. To derive a risk score for mortality, a machine learning approach was utilized. To maximize statistical power while examining replicability, the sample was split into discovery (n=99) and replication (n=50) subsamples. Elastic-net regression was used to identify a linear prediction model. Youden's index was used to identify appropriate cutoffs. Cox proportional hazards regression was used to examine mortality risk; model concordance and hazards ratios were reported. RESULTS: One-quarter of the patients survived for three years after initiation of cCRT. Prognostic factors for survival in the discovery group included age, sex, smoking status, albumin, histology, largest tumor size, number of nodal stations, stage, induction therapy, and radiation dose. The derived model had good risk predictive accuracy (C=0.70). Median survival time was shorter in the high-risk group (0.93 years) vs the low-risk group (2.40 years). Similar findings were noted in the replication sample with strong model accuracy (C=0.69) and median survival time of 0.93 years and 2.03 years for the high- and low-risk groups, respectively. CONCLUSION: This novel risk prediction model for overall survival in patients with stage III NSCLC highlights the importance of integrating patient, clinical, and treatment variables for accurately predicting outcomes. Clinicians can use this tool to make personalized treatment decisions for patients with locally advanced NSCLC treated with concurrent chemo-radiation.

Anti-PD-1-Related Exacerbation of Interstitial Lung Disease in a Patient with Non-Small Cell Lung Cancer: A Case Presentation and Review of the Literature.

Immunotherapy is standard first-line therapy for advanced non-small cell lung cancer (NSCLC) either alone or in combination with chemotherapy. Despite significant benefits, immune checkpoint inhibitors (ICI) can cause toxicities within any organ, termed immune related adverse events. Pneumonitis is a potentially life-threatening complication of ICIs. Currently, there are no established guidelines for use of ICIs in patients with underlying autoimmune or interstitial lung disease (ILD) and few studies have been published. We present a case of first-line ICI-chemotherapy in a patient with metastatic NSCLC and ILD who suffered treatment related lung toxicity and acute worsening ILD, which lead to his death.

Fatal Adverse Events Associated with Pembrolizumab in Cancer Patients: A Meta-Analysis.

Background: Pembrolizumab as an immune checkpoint inhibitor (ICI) has emerged as an effective treatment for many cancers. It has unique immune-related adverse events (irAE) and little is known about its risk of fatal adverse events (FAEs). We conducted a meta-analysis of clinical trials to determine the incidence and risk of FAEs with pembrolizumab.Methods: A systematic search for phase I-III clinical trials of pembrolizumab was conducted using databases including PUBMED and abstracts presented at the American Society of Clinical Oncology (ASCO) conferences until October 2018. Eligible studies included prospective clinical trials of pembrolizumab with available data on FAE. Data on FAE was extracted from each study and pooled for calculations. Incidence, relative risk (RR) and 95% confidence intervals (CI) were calculated by employing fixed or random-effects models.Results: A total of 11 clinical trials with 3713 patients were included for analysis. The overall incidence of FAE with pembrolizumab was 1.2% (95% CI: 0.5-2.8%). The incidence of FAE significantly varied among different tumor types (p = .02), ranging from 0.2% in melanoma to 3.1% in breast cancer, and with its combination with chemotherapy (0.7%, 95% CI: 0.4-1.2% versus 7.0%, 95% CI: 4.9-10%; p<.01). Chemotherapy plus pembrolizumab 7.0% (95%CI: 4.9-10) as compared to pembrolizumab alone 0.7%, (95% CI: 0.4-1.2; p < .001). There was no significant difference in the risk of FAEs when pembrolizumab was compared with chemotherapy with RR = 1.24 (95% CI: 0.8-1.89; p = .31). The most common FAEs were due to infectious complication (26.5%), cardiac toxicity (14.7%) and pneumonitis (13.2%).Conclusions: The risk of FAEs with pembrolizumab may be similar to chemotherapy in cancer patients and may vary with tumor types and its combination with chemotherapy.

Interventional endoscopy in the diagnosis and management of pancreatic adenocarcinoma.

Pancreatic cancer accounts for approximately 3% of all cancers in US, and is the fourth leading cause of mortality in both men and women. It is a silent killer due to lack of early symptoms and the majority of patients present at advanced stage at the time of initial diagnosis. Only 15-20% of patients are candidates for curative resection and even then, the 5-year survival rates range from 10-25%. Despite recent advances in the treatment of advanced pancreatic cancer, the prognosis remains grim with 5-year overall survival (OS) of approximately 10%. Early detection is key for improving patient outcomes in this lethal disease. Contributing to the difficulty in the diagnosis and management is the anatomic location of the pancreas within the abdomen (retroperitoneal location and being adjacent to hollow viscus, solid organs and major vessels), and suboptimal response to systemic chemotherapy. Multimodality imaging (pancreatic protocol CT and MRI/MRCP) is often used for the diagnosis and staging of pancreatic adenocarcinoma. Interventional endoscopy is a relatively new field, and with Endoscopic techniques becoming more advanced, their role in diagnosis and management of pancreatic cancer is expanding rapidly. Endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS) are the two main modalities used in cases of pancreatic neoplasms.

Anti-vascular endothelial growth factor antibody bevacizumab reduced the risk of anemia associated with chemotherapy-A meta-analysis.

INTRODUCTION: Vascular endothelial growth factor (VEGF) may play a role in erythropoiesis. We performed a meta-analysis of randomized controlled trials (RCT) to determine the effect of the anti-VEGF antibody bevacizumab on anemia in cancer patients treated with chemotherapy. METHODS: Databases from PUBMED, the Web of Science, Embase, the Cochrane Library, and abstracts presented at the American Society of Clinical Oncology (ASCO) conferences until May 2010 were searched to identify relevant studies. Eligible studies included prospective RCTs in which the combination of bevacizumab and chemotherapy was compared with chemotherapy alone. Summary incidence rate, relative risk (RR), and 95% confidence interval (CI) were calculated. RESULTS: A total of 6439 patients with a variety of solid tumors were included for analysis from 11 RCTs. Among those patients receiving bevacizumab and chemotherapy, the incidences of all-grade and high-grade (grade 3 and above) anemia were 17.8% (95% CI: 11.1-27.1%) and 2.8% (95% CI: 1.6-5.0%) respectively. In comparison with chemotherapy alone, bevacizumab significantly reduced all-grade (RR, 0.79; 95% CI: 0.66-1.0, p = 0.007) and high-grade anemia (RR, 0.72; 95% CI: 0.57-0.90, p = 0.005). The effect did not vary significantly among bevacizumab doses (p = 0.88), tumor types (p = 0.75) or chemotherapy regimens (p = 0.98). DISCUSSION: Bevacizumab may significantly reduce the risk of anemia with chemotherapy in cancer patients.

Increased risk of serious hemorrhage with bevacizumab in cancer patients: a meta-analysis.

BACKGROUND: The role of the widely-used angiogenesis inhibitor bevacizumab in the development of serious hemorrhage is not well defined in cancer patients. This study was conducted to determine the overall risk of hemorrhage with bevacizumab by a systematic review and meta-analysis of randomized controlled trials (RCT). METHODS: Databases from PubMed and the Web of Science from January 1966 to May 2009 and abstracts presented at the American Society of Clinical Oncology (ASCO) conferences from January 2000 to May 2009 were searched to identify relevant studies. Eligible studies included prospective RCTs in which bevacizumab was compared to controls concurrently with antineoplastic therapy. Summary incidence rates, relative risks (RR), and 95% confidence intervals (CI) were calculated employing fixed- or random-effects models. RESULTS: A total of 12,617 patients with a variety of solid tumors from 20 RCTs were included for analysis. The incidence of all-grade hemorrhage was 30.4% (95% CI 21.5-40.9), with 3.5% (95% CI 2.2-5.7%) being high grade (grade 3-5). Overall, bevacizumab significantly increased the risk of bleeding with an RR of 2.48 (95% CI 1.93-3.18) when compared to the controls, with RRs of 3.02 (95% CI 2.42-3.78) and 2.01 (95% CI 1.43-2.83) at 5 and 2.5 mg/kg/week, respectively. Significantly increased risks for epistaxis or pulmonary hemorrhage were observed. In addition, bevacizumab significantly increased the risk of high-grade bleeding with an RR of 1.91 (95% CI 1.36-2.68). The risk of fatal bleeding was low (0.8%; 95% CI 0.4-1.7), and significantly elevated only in lung cancer (RR 5.02; 95% CI 1.52-16.66). CONCLUSION: Bevacizumab may significantly increase the risk of serious hemorrhage in cancer patients.