Phase II Randomized Trial of Carboplatin, Pemetrexed, and Bevacizumab With and Without Atezolizumab in Stage IV Nonsquamous Non-Small-Cell Lung Cancer Patients Who Harbor a Sensitizing EGFR Mutation or Have Never Smoked.

Introduction: Patients with non-small-cell lung cancer (NSCLC) who have never smoked or have tumors with mutations in EGFR generally derive minimal benefit from single-agent PD-1/PD-L1 checkpoint inhibitors. Prior data indicate that adding PD-L1 inhibition to anti-VEGF and cytotoxic chemotherapy may be a promising approach to overcoming immunotherapy resistance in these patients, however prospective validation is needed. This trial in progress (NCT03786692) is evaluating patients with stage IV NSCLC who have never smoked or who have tumors with sensitizing EGFR alterations to determine if a 4-drug combination of atezolizumab, carboplatin, pemetrexed, and bevacizumab can improve outcomes compared to carboplatin, pemetrexed and bevacizumab without atezolizumab.

Association of Immune-Related Adverse Events With Efficacy of Atezolizumab in Patients With Non-Small Cell Lung Cancer: Pooled Analyses of the Phase 3 IMpower130, IMpower132, and IMpower150 Randomized Clinical Trials.

Importance: Immune-related adverse events (irAEs) arising from immune checkpoint inhibitor (ICI) cancer therapy may potentially predict improved outcomes.

Objective: To evaluate the association between irAEs and atezolizumab efficacy in patients with advanced non-small cell lung cancer (NSCLC) using pooled data from 3 phase 3 ICI studies.

Design, Setting, And Participants: IMpower130, IMpower132, and IMpower150 were phase 3, multicenter, open-label, randomized clinical trials to evaluate the efficacy and safety of chemoimmunotherapy combinations involving atezolizumab.

Tumor Microenvironment before and after Chemoradiation in Locally Advanced Rectal Cancer: Beyond PD-L1.

Background: In locally advanced rectal cancer treatment, neoadjuvant concurrent chemoradiation therapy (cCRT) is the standard of care. The tumor microenvironment (TME) is a complex entity comprising of tumor cells, immune cells and surrounding stroma and is closely associated with tumor growth and survival, response to antitumor therapies and also resistance to treatment. We aimed to assess the change in biomarkers associated with TME following standard neoadjuvant cCRT in rectal cancer.

Prognostic and predictive biomarkers for response to neoadjuvant chemoradiation in esophageal adenocarcinoma.

Background: Esophageal adenocarcinoma is a lethal disease. For locally advanced patients, neoadjuvant chemoradiotherapy followed by surgery is the standard of care. Risk stratification relies heavily on clinicopathologic features, particularly pathologic response, which is inadequate, therefore establishing the need for new and reliable biomarkers for risk stratification.

Rechallenging Fluoropyrimidine-Induced Cardiotoxicity and Neurotoxicity: A Report of Two Cases.

Fluoropyrimidines (FP's) such as fluorouracil (5-FU) and capecitabine are antimetabolites widely used in many solid tumors. FPs side effects are caused mainly by a lack of dihydropyrimidine dehydrogenase (DPD) enzyme. It has been noticed that treatment with infusional regimens of 5-FU is associated with more adverse events (AE) compared to bolus forms.

IMpower150 Final Exploratory Analyses for Atezolizumab Plus Bevacizumab and Chemotherapy in Key NSCLC Patient Subgroups With EGFR Mutations or Metastases in the Liver or Brain.

Introduction: Final overall survival (OS) analyses are presented for EGFR mutations and liver or brain metastases subgroups in the phase 3 IMpower150 study (NCT02366143) evaluating atezolizumab plus bevacizumab plus carboplatin and paclitaxel (ABCP) or atezolizumab plus carboplatin and paclitaxel (ACP) versus bevacizumab plus carboplatin and paclitaxel (BCP).

Methods: Overall, 1202 patients (intention-to-treat population) with chemotherapy-naive, metastatic, nonsquamous NSCLC were randomized to ABCP, ACP, or BCP. Patients with treated, stable brain metastases were permitted.

IMpower150 Final Overall Survival Analyses for Atezolizumab Plus Bevacizumab and Chemotherapy in First-Line Metastatic Nonsquamous NSCLC.

Introduction: We report the final overall survival (OS) analyses of atezolizumab-carboplatin-paclitaxel (ACP [experimental arm]) and OS data with approximately 39.8 months of median follow-up with atezolizumab-bevacizumab-carboplatin-paclitaxel (ABCP) versus bevacizumab-carboplatin-paclitaxel (BCP) in chemotherapy-naive patients with metastatic nonsquamous NSCLC in the phase 3 IMpower150 study (NCT02366143).

Methods: In this randomized, open-label study (N = 1202), coprimary end points included investigator-assessed progression-free survival and OS in intention-to-treat (ITT) wild-type (WT; no EGFR or ALK alterations) patients.

Association of Celiac Disease With Pembrolizumab.

Immune checkpoint inhibitors (ICIs) in the recent times have transformed the landscape of the management of many solid tumors. Unfortunately, many immune-related adverse effects are associated with ICIs, which lead to a negative outcome in cancer treatment. We present a case of a 63-year-old female with metastatic adenocarcinoma of unknown origin, who developed celiac disease during the course of treatment with pembrolizumab.

The use of immunotherapy treatment in malignant pheochromocytomas/paragangliomas: a case report.

Background: Pheochromocytomas are a subset of paragangliomas, which are a rare group of neural crest cell-derived tumors. Malignant cases of both pheochromocytomas and paragangliomas are even rarer, and currently there is no standard of care. This case report details the use of off-label immunotherapy and its efficacy in the management of the aforementioned tumor.

Chemotherapy use in early stage anal canal squamous cell carcinoma and its impact on long-term overall survival

Background: The standard of care for non-metastatic squamous cell carcinoma of the anal canal (SCCA) is concurrent chemoradiotherapy. It is postulated that chemotherapy could be omitted for the earliest stages without worsening outcomes.

Methods: We queried the NCDB from 2004-2016 for patients with cT1N0M0 SCCA treated non-operatively with radiation, with and without chemotherapy, and at least two months of follow-up.

Intratumoral immunotherapy with STING agonist, ADU-S100, induces CD8+ T-cell mediated anti-tumor immunity in an esophageal adenocarcinoma model.

Background: Esophageal adenocarcinoma (EAC) is a deadly disease with limited treatment options. STING is a transmembrane protein that activates transcription of interferon genes, resulting in stimulation of APCs and enhanced CD8+ T-cell infiltration. The present study evaluates STING agonists, alone and in combination with radiation to determine durable anticancer activity in solid tumors.

Epidemiology and Retrospective Analysis in Extrapulmonary Neuroendocrine Carcinoma.

Objectives: We conducted a retrospective analysis of patients with extrapulmonary neuroendocrine carcinomas (EPNECs) to explore the distribution and overall outcomes by different regimens and their primary sites.

Setting: We reviewed the outcomes of one of the largest data sets of patients with extrapulmonary small cell carcinomas (EPSCCs) identified at Allegheny General Hospital located in Pittsburgh, Pennsylvania, USA.

Participants: Patients diagnosed with grade 3 EPNECs were retrospectively identified.

A Retrospective Analysis of Factors Affecting Palliative Care Consults in Patients Undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

Purpose This study was conducted to determine factors that influence palliative care (PC) consultation in patients receiving cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). Patient and methods We queried our Electronic Medical Record EPIC for a list of patients who underwent cytoreductive surgery with HIPEC or hyperthermic intrathoracic chemotherapy (HITEC) in the hospital from April 2016-April 2019. Data was manually extracted and patients who did not meet our criteria were excluded.

Factors associated with treatment receipt and overall survival for patients with locally advanced large cell neuroendocrine carcinoma of the lung: A National Cancer Database analysis.

Purpose: Large cell neuroendocrine carcinoma (LCNEC) is a rare pulmonary malignancy with clinicopathologic features of both non-small cell lung cancer (NSCLC) and small-cell lung cancer (SCLC). Given the paucity of available data regarding LCNEC management, we queried the National Cancer Database (NCDB) to describe trends in management, identify predictors of treatment receipt, and compare outcomes in patients receiving chemotherapy (ChT) and chemoradiotherapy (CRT).

Methods: We identified patients with locally advanced (Stage III) LCNEC of the lung treated with definitive ChT or CRT between the years of 2004-2015.

Post-Operative Morbidity and Mortality Following Total Neoadjuvant Therapy Versus Conventional Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer.

Background: Standard of care for locally advanced rectal cancer (LARC) (stage II/III) includes preoperative chemoradiation (CRT) followed by resection and adjuvant chemotherapy. Total neoadjuvant therapy (TNT) is a new treatment paradigm that delivers systemic therapy prior to CRT aimed at improving outcomes for high-risk patients. Here we analyzed the national cancer database (NCDB) comparing short-term post-operative outcomes between patients receiving TNT and CRT.

Impact of affordable care act on the treatment and outcomes for stage-IV colorectal cancer.

Background: Patients with advanced cancers are among the most vulnerable group of patients. We sought to analyze the impact of Affordable Care Act (ACA) on the interaction of socioeconomic factors with treatment and survival in patients with metastatic colorectal cancers.

Methods: National Cancer Database (NCDB) was queried for patients with Stage-IV colon(CCa) and rectal cancers(R-Ca) diagnosed 2004-2015 and excluded those who did not receive any therapies within 6 months of diagnosis.

Molecular Profiling of Advanced Malignancies: A Community Oncology Network Experience and Review of Literature.

Many genomic alterations have been identified that are critical to the malignant phenotype. Some of these, termed "driver mutations," are critical for tumor proliferation and progression. The landscape of targeted therapy has expanded as well.

Incidence and risk factors for post-operative mortality, hospitalization, and readmission rates following pancreatic cancer resection.

Background: The only potentially curative approach for pancreatic cancer is surgical resection, but this technically challenging procedure carries risks for postoperative morbidities and mortality. This study of a large, contemporary national database illustrates incidences of, and risk factors for, post-procedural mortality, prolonged hospital stay, and 30-day readmission.

Methods: From the National Cancer Database (NCDB), stage I-III pancreatic adenocarcinomas were identified [2004-2015].

Surgical resection versus stereotactic body radiation therapy in early stage bronchopulmonary large cell neuroendocrine carcinoma.

Background: Surgery is the standard of care for early stage non-small cell lung cancer (NSCLC). Stereotactic body radiotherapy (SBRT) is another definitive treatment option for those patients who have not been treated surgically. Comparison of approaches is being explored in NSCLC, but has yet to be compared exclusively in large cell neuroendocrine carcinoma (LCNEC) of the lung.

Utilization of Adjuvant Radiotherapy for Resected Colon Cancer and Its Effect on Outcome.

Background: Adjuvant radiation is generally not recommended for colon cancer but may be considered in certain clinical scenarios [advanced local disease (pT4) and/or positive margins]. Guidelines in this area are lacking; thus we analyzed the National Cancer Database (NCDB) for patterns of care in this regard and any predictors for outcome.

Methods: We queried the NCDB from 2004 to 2016 for patients with resected adenocarcinoma of the colon having pT4 and/or had positive margins on final pathology and who received adjuvant multiagent chemotherapy.

Retrospective review of total neoadjuvant therapy.

Background: Neoadjuvant chemoradiotherapy (nCRT) followed by resection and postoperative multi-agent chemotherapy (maChT) is the standard of care for locally advanced rectal cancer. Using this approach, maChT administration can be delayed for several months, leading to concern for distant metastases. To counteract this, a novel treatment approach known as total neoadjuvant therapy (TNT) has gained popularity, in which patients receive both maChT and nCRT prior to resection.

Long-term outcomes by response to neoadjuvant chemotherapy or chemoradiation in patients with resected pancreatic adenocarcinoma.

Background: Response of pancreatic adenocarcinoma to neoadjuvant chemotherapy (nCT) or chemoradiotherapy (nCRT) may be associated with prognosis, but long-term outcomes based on response to neoadjuvant therapy have not been well evaluated to date.

Methods: The National Cancer Database was queried for patients with pancreatic adenocarcinoma receiving nCT/nCRT. To evaluate response to nCT/nCRT, comparisons were made from cT and cN stage to the respective post-neoadjuvant therapy ypT and ypN stages.

Definitive Chemoradiation for Rectal Cancer: Is There a Role for Dose Escalation? A National Cancer Database Study.

Background: Surgery remains the standard of care in rectal cancer. Select patients will not undergo surgery for reasons such as medical inoperability or a watch-and-wait approach and instead are managed with definitive chemoradiation.

Objective: We used the National Cancer Database to identify overall survival and predictors thereof in the nonoperative management of patients with rectal cancer.

Time to Adjuvant Systemic Therapy Following Pancreatic Cancer Resection and Effect on Outcome.

Objectives: The appropriate timing of chemotherapy following surgery for resectable pancreatic adenocarcinoma is controversial. Using the National Cancer Database we evaluated time to initiation of chemotherapy postresection and correlated with outcome.

Methods: We identified stage I-III pancreatic adenocarcinoma treated surgically with adjuvant chemoradiotherapy.

Anal adenocarcinoma: Treatment outcomes and trends in a rare disease entity.

Importance: Primary Adenocarcinoma of the anus is a rare disease with a poor prognosis and thus tends to have a more aggressive treatment algorithm, typically involving a surgical approach. Prior to 2001, a few retrospective studies outlined improved outcomes with the incorporation of surgery with chemoradiation. However, since the publication of these studies, advancement in radiotherapy modalities and imaging have left the question of improved outcomes while reserving surgery for salvage.