Understanding the increasing incidence of neuroendocrine tumors.

INTRODUCTION: Neuroendocrine tumors (NETs) are a diverse group of tumors with origins from different primary sites such as gastro-entero-pancreatic, lung and endocrine tissue. Worldwide, their incidence has increased in recent decades. Advances in imaging and better clinical awareness are traditionally attributed to this trend; however, other factors such as genetic and environmental contributors are appreciated as well. AREAS COVERED: The purpose of this article is to review the worldwide epidemiologic trends in incidence of NET through the decades and discuss the various factors potentially contributing to the observed changes in incidence trends. EXPERT OPINION: Overall, the incidence of NET has increased across the globe over the last few decades. Although multiple genetics and environmental factors have been proposed, the majority of this increase in incidence is secondary to earlier detection. Future studies will help in more accurate assessments and an improved understanding of disease incidence among patients with different grades and differentiation.

The Role of Systemic Therapy in Resectable Colorectal Liver Metastases: Systematic Review and Network Meta-Analysis.

BACKGROUND: Despite multiple randomized trials, the role of perioperative chemotherapy in colorectal cancer liver metastasis (CRLM) is still under debate. In this systematic review and network meta-analysis (NMA), we aim to evaluate the efficacy of perioperative systemic therapies for patients with CRLM. METHODS: We searched various databases for abstracts and full-text articles published from database inception through May 2021.We included randomized controlled trials (RCTs) comparing the addition of perioperative (post, pre, or both) systemic therapies to surgery alone in patients with CRLM. The outcomes were compared according to the chemotherapy regimen using a random effects model. Outcomes of interest included disease-free survival (DFS) and overall survival (OS). RESULTS: Seven RCTs with a total of 1504 patients with CRLM were included. Six studies included post-operative treatment and one evaluated perioperative (pre- and postoperative) therapy. Fluoropyrimidine-based chemotherapy was the most used systemic therapy. NMA showed benefit of adding perioperative therapy to surgery in terms of DFS (HR 0.73, 95% CI 0.63 to 0.84). However, these findings did not translate into a statistically significant OS benefit (HR 0.88, 95% CI 0.74 to 1.05). NMA did not show any advantage of one regimen over another including oxaliplatin or irinotecan. CONCLUSIONS: This systematic review and NMA of 7 RCTs found that the addition of perioperative systemic treatment for resectable CRLM could improve disease-free survival but not overall survival. Based on the findings, addition of perioperative treatment in resectable CRLM should be individualized weighing the risks and benefits.

Hypertension in Cancer Survivors.

PURPOSE OF REVIEW: With increasing survival after cancer treatment, there is a need for long-term management of risk factors and chronic medical conditions to realize the full benefit of improvement of outcomes. Hypertension is a major risk factor for cardiovascular disease and has a higher prevalence in cancer survivors compared to the general population. In this review article, we discuss the burden of hypertension in cancer survivors and how this impacts their long-term outcomes and risk of cancer recurrence. We then discuss the latest concepts regarding the pathophysiology of hypertension in cancer survivors in detail. There is a focus on inflammation and the role it plays in cancer and hypertension followed by a brief discussion on clonal hematopoiesis of indeterminate potential (CHIP) and associated hypertension. There is a brief review of various cancer therapies associated with development and worsening of hypertension control and the underlying mechanisms behind this. We conclude the review article by giving recommendations on blood pressure control in this unique patient population. RECENT FINDINGS: A lot of newer anti-cancer therapies have been implicated in the development or worsening of hypertension. We summarize the latest data, explore associations between these therapies and hypertension, and review the latest understanding of the underlying mechanisms driving this process. Hypertension is a major risk factor for cardiovascular disease in cancer survivors and must be recognized and treated promptly.

The treatment landscape for gastroesophageal adenocarcinomas.

The treatment landscape for gastroesophageal adenocarcinomas has significantly changed over the last year. The addition of nivolumab to first-line chemotherapy has led to survival benefit in patients who have metastatic gastroesophageal adenocarcinoma with a programmed death ligand 1 combined positive score of 5 or greater. Similarly, in patients with metastatic human epidermal growth factor receptor 2 (HER2)-positive gastroesophageal adenocarcinoma, the addition of pembrolizumab to chemotherapy and trastuzumab has significantly improved efficacy. Furthermore, a phase 2 study revealed that trastuzumab deruxtecan, a new antibody-drug conjugate, significantly improved survival in comparison with chemotherapy among patients with HER2-positive gastric cancer in the refractory setting, and it produced a signal of efficacy in the second-line setting. Chemoimmunotherapy combinations are now considered the standard of care for a significant number of patients with gastroesophageal adenocarcinomas.

Second-Line Treatment Options for Hepatocellular Carcinoma: Current Landscape and Future Direction.

Hepatocellular carcinoma is a leading cause of mortality worldwide, and its incidence is rising. The last few years have witnessed a proliferation of available systemic therapeutic options, with the approval of multiple agents, including immune checkpoint inhibitors and drugs targeting vascular endothelial growth factor, such as cabozantinib, regorafenib, and ramucirumab. Most recently, the combination of atezolizumab plus bevacizumab has resulted in the longest overall survival yet known in hepatocellular carcinoma, therefore changing the preferred first-line treatment from the previous options of sorafenib and lenvatinib. The aim of this review is to summarize the available clinical data for the current second-line systemic treatment options and the future perspectives in the treatment landscape of hepatocellular carcinoma.

Continuing cancer care delivery during the peak of COVID-19 in the Bronx, New York: experience from a public teaching hospital.

INTRODUCTION: We report our experience with cancer care delivery during the peak of COVID-19 pandemic in New York City. METHODS: Retrospective analysis of the patients treated from the 1st of March, 2020 to the 8th of May, 2020. RESULTS: Team huddles, infection screening and patient selection strategies were implemented. One hundred and seventy patients were treated in 576 visits. Six developed severe COVID-19 requiring hospitalization, two died. Their median Charlson Comorbidity Index was 9, higher than the rest of the cohort. CONCLUSIONS: Cancer care delivery is safe and feasible using an approach focused on careful patient selection, team communication and infection control.

Efficacy of Upfront Docetaxel With Androgen Deprivation Therapy for Castration-Sensitive Metastatic Prostate Cancer Among Minority Patients.

BACKGROUND: Upfront docetaxel (UD) with androgen deprivation therapy (ADT) has been demonstrated to improve survival outcomes in metastatic castration-sensitive prostate cancer (mCSPC). However, existing studies have included predominantly Caucasian patients. STUDY QUESTION: To compare the efficacy of addition of UD to ADT in mCSPC to ADT alone among minority patients. STUDY DESIGN: Retrospective study of mCSPC patients. MEASURES AND OUTCOMES: Patients treated with UD and ADT between January 2014 and December 2017 (UD + ADT, n = 44) were compared with those treated with ADT alone between January 2008 and January 2017 (ADT, n = 38); patients of Caucasian ethnicity were excluded. The outcome of interest was progression-free survival (PFS), which was estimated using Kaplan-Meier analysis and Cox proportional hazard analysis. RESULTS: Overall, 63 (76.8%) patients were African American and 16 (19.5%) were Hispanic. Fifty-five (67%) patients had high-volume mCSPC. The median follow-up was 14 months [95% confidence interval (CI): 10.4-16.5] for UD + ADT and 42 months (95% CI: 17-66.9) for ADT. Median PFS did not differ between groups: UD + ADT: 16 versus ADT: 18 months [hazard ratio (HR) for UD + ADT = 0.88, 95% CI: 0.48-1.62; P = 0.70]. In patients with high-volume disease, median PFS remained similar (UD + ADT: 16 vs. ADT: 14 months (HR for UD + ADT = 0.64, 95% CI: 0.33-1.25; P = 0.19). On multivariable analysis, prolonged time to nadir PSA, HR = 0.83 (95% CI: 0.76-0.90), was independently associated with PFS. The most common toxicities in UD + ADT were anemia and fatigue. Major limitations include small sample size and potential for selection bias due to the retrospective study design. CONCLUSIONS: In this retrospective review of a minority mCSPC cohort, UD + ADT was not associated with improved PFS compared with ADT alone. Although further study with larger sample size is needed, these results underscore the importance of ensuring accrual of minorities in clinical trials, reflective of the real-world setting.

Epidermal Growth Factor Receptor-mutated Lung Cancer as the Initial Manifestation of Germline TP53 Mutation Associated Cancer.

Epidermal growth factor receptor (EGFR) mutation-driven lung cancer is a rare occurrence in patients with Li-Fraumeni syndrome (LFS) characterized by germline mutations in the tumor protein 53 (TP53) gene. Here we describe a case of primary EGFR mutation-driven lung adenocarcinoma in a young woman with LFS. There is only one other reported case with such presentation. We review the interactions between the TP53 gene and EGFR pathways facilitating lung carcinogenesis. We also review other cases with similar presentations described in the literature and the response to tyrosine kinase inhibitors (TKI) in this rare patient population.

Individual rac GTPases mediate aspects of prostate cancer cell and bone marrow endothelial cell interactions.

The Rho GTPases organize the actin cytoskeleton and are involved in cancer metastasis. Previously, we demonstrated that RhoC GTPase was required for PC-3 prostate cancer cell invasion. Targeted down-regulation of RhoC led to sustained activation of Rac1 GTPase and morphological, molecular and phenotypic changes reminiscent of epithelial to mesenchymal transition. We also reported that Rac1 is required for PC-3 cell diapedesis across a bone marrow endothelial cell layer. In the current study, we queried whether Rac3 and RhoG GTPases also have a role in prostate tumor cell diapedesis. Using specific siRNAs we demonstrate roles for each protein in PC-3 and C4-2 cell adhesion and diapedesis. We have shown that the chemokine CCL2 induces tumor cell diapedesis via Rac1 activation. Here we find that RhoG partially contributes to CCL2-induced tumor cell diapedesis. We also find that Rac1 GTPase mediates tight binding of prostate cancer cells to bone marrow endothelial cells and promotes retraction of endothelial cells required for tumor cell diapedesis. Finally, Rac1 leads to ß1 integrin activation, suggesting a mechanism that Rac1 can mediate tight binding with endothelial cells. Together, our data suggest that Rac1 GTPase is key mediator of prostate cancer cell-bone marrow endothelial cell interactions.