The impact of immune-related adverse events on survival outcomes in a racially diverse population, with a focus on non-Hispanic Black patients.

Introduction: The development of immune-related adverse events (irAEs) has been associated with improved survival outcomes in non-small cell lung cancer (NSCLC). However, this association's extent across race and ethnicity remains uncertain. We evaluated the association between the development of irAEs and treatment outcomes across racially diverse groups treated at a safety net hospital.

Phase 3 Trial of Cabozantinib to Treat Advanced Neuroendocrine Tumors.

Background: Treatment options for patients with advanced neuroendocrine tumors are limited. The efficacy of cabozantinib in the treatment of previously treated, progressive extrapancreatic or pancreatic neuroendocrine tumors is unclear.

Methods: We enrolled two independent cohorts of patients - those with extrapancreatic neuroendocrine tumors and those with pancreatic neuroendocrine tumors - who had received peptide receptor radionuclide therapy or targeted therapy or both.

Diagnosis and Management of Parathyroid Carcinoma.

Parathyroid carcinoma (PC) is a rare malignancy, often characterized by the unregulated secretion of parathyroid hormone. The sequelae of severe hypercalcemia together with direct complications from tumor dissemination in patients with advanced disease are usually fatal. Due to its rarity, formal studies to guide the diagnosis and management of parathyroid carcinoma are lacking.

Real-World comprehensive genomic profiling data for diagnostic clarity in pulmonary Large-Cell neuroendocrine carcinoma.

Background: Pulmonary large-cell neuroendocrine carcinoma (LCNEC) is an uncommon subtype of lung cancer believed to represent a spectrum of tumors sharing characteristics of both small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). Other groups have proposed genomic LCNEC subtypes, including small cell-like, non-small cell-like, and carcinoid-like subtypes. The primary goal of this study was to better define the NSCLC-like subtype with comprehensive genomic profiling (CGP).

Intertumoral lineage diversity and immunosuppressive transcriptional programs in well-differentiated gastroenteropancreatic neuroendocrine tumors.

Neuroendocrine tumors (NETs) are rare cancers that most often arise in the gastrointestinal tract and pancreas. The fundamental mechanisms driving gastroenteropancreatic (GEP)-NET growth remain incompletely elucidated; however, the heterogeneous clinical behavior of GEP-NETs suggests that both cellular lineage dynamics and tumor microenvironment influence tumor pathophysiology. Here, we investigated the single-cell transcriptomes of tumor and immune cells from patients with gastroenteropancreatic NETs.

Sex differences on multikinase inhibitors toxicity in patients with advanced gastroenteropancreatic neuroendocrine tumours.

Purpose: There is an increasing interest in the role of sex and gender in cancer patients. The impact of sex differences in oncological systemic therapies is still unknown, and there is a lack of evidence specially in uncommon neoplasms like neuroendocrine tumours (NET). In the present study, we combine the differential toxicities by sex in five published clinical trials with multikinase inhibitors (MKI) in gastroenteropancreatic (GEP) NET.

Randomized Study of Temozolomide or Temozolomide and Capecitabine in Patients With Advanced Pancreatic Neuroendocrine Tumors (ECOG-ACRIN E2211).

Purpose: Patients with advanced pancreatic neuroendocrine tumors (NETs) have few treatment options that yield objective responses. Retrospective and small prospective studies suggest that capecitabine and temozolomide are associated with high response rates (RRs) and long progression-free survival (PFS).

Patients And Methods: E2211 was a multicenter, randomized, phase II trial comparing temozolomide versus capecitabine/temozolomide in patients with advanced low-grade or intermediate-grade pancreatic NETs.

SDHx mutations and temozolomide in malignant pheochromocytoma and paraganglioma.

Malignant pheochromocytomas (PHEOs)/paragangliomas (PGLs) are rare tumors for which clinical outcomes remain poorly defined and therapeutic options are limited. Approximately 27% carry pathogenic germline succinate dehydrogenase (SDHx) mutations; the presence of such mutations has been correlated with response to temozolomide (TMZ). We aimed to investigate the association between germline mutations in SDHx and response to TMZ.

Everolimus with or without bevacizumab in advanced pNET: CALGB 80701 (Alliance).

Treatment with the MTOR inhibitor everolimus improves progression-free survival (PFS) in pancreatic neuroendocrine tumors (pNETs), but it is not known if the addition of a VEGF pathway inhibitor to an MTOR inhibitor enhances antitumor activity. We performed a randomized phase II study evaluating everolimus with or without bevacizumab in patients with advanced pNETs. One hundred and fifty patients were randomized to receive everolimus 10 mg daily with or without bevacizumab 10 mg/kg i.

Clinical Implications of Pathogenic Germline Variants in Small Intestine Neuroendocrine Tumors (SI-NETs).

Purpose: An inherited basis for presumed sporadic neuroendocrine tumor (NET) has been suggested by evidence of familial clustering of NET and a higher incidence of second malignancies in patients and families with NET. To further investigate a potential heritable basis for sporadic neuroendocrine tumors, we performed multigene platform germline analysis to determine the frequency of hereditary susceptibility gene variants in a cohort of patients with sporadic small intestine NET (SI-NET).

Methods: We performed a multigene platform germline analysis with Invitae's 83-gene, next-generation sequencing panel using DNA from 88 individuals with SI-NET from a clinically annotated database of patients with NET evaluated at Dana-Farber Cancer Institute (DFCI) who are considered high risk for inherited variants.

Weight Maintenance up to 48 Weeks in Patients With Carcinoid Syndrome Treated With Telotristat Ethyl: Pooled Data From the Open-Label Extensions of the Phase III Clinical Trials TELESTAR and TELECAST.

Reported incidences of neuroendocrine tumors (NETs) appear to be increasing, possibly due to greater disease awareness and increased accuracy of diagnosis. Approximately 20% of patients with NETs develop carcinoid syndrome (CS), which arises from elevated secretion of bioactive compounds, including serotonin, from NETs. This leads to symptoms including diarrhea and flushing, which result in weight loss and are associated with considerable negative impact on patients' quality of life.

Validation of a Crisis Standards of Care Model for Prioritization of Limited Resources During the Coronavirus Disease 2019 Crisis in an Urban, Safety-Net, Academic Medical Center.

Objectives: The coronavirus disease 2019 pandemic has overwhelmed healthcare resources even in wealthy nations, necessitating rationing of limited resources without previously established crisis standards of care protocols. In Massachusetts, triage guidelines were designed based on acute illness and chronic life-limiting conditions. In this study, we sought to retrospectively validate this protocol to cohorts of critically ill patients from our hospital.

Long-Term Treatment with Telotristat Ethyl in Patients with Carcinoid Syndrome Symptoms: Results from the TELEPATH Study.

Introduction: Telotristat ethyl is indicated for use in combination with somatostatin analogs (SSAs) to treat carcinoid syndrome (CS) diarrhea uncontrolled by SSAs alone in adults, but long-term safety and efficacy data beyond 48 weeks are needed.

Objectives: The aims of the study were to evaluate the long-term safety and tolerability of telotristat ethyl and its effect on quality of life (QOL) in patients with CS.

Methods: In this phase 3, nonrandomized, multicenter, open-label, long-term extension study (TELEPATH), patients who participated in phase 2 or 3 trials of telotristat ethyl continued treatment at their present dose level (250 or 500 mg thrice daily) for 84 weeks.

Recurrence Patterns After Surgical Resection of Gastroenteropancreatic Neuroendocrine Tumors: Analysis From the National Comprehensive Cancer Network Oncology Outcomes Database.

Objective: Current National Comprehensive Cancer Network guidelines for gastroenteropancreatic neuroendocrine tumors (GEPNETs) recommend complete (R0) surgical resection of the primary tumor and metastases, if feasible. However, large multicenter studies of recurrence patterns of GEPNETs after resection have not been performed.

Methods: Patients 18 years or older who presented to 7 participating National Comprehensive Cancer Network institutions between 2004 and 2008 with a new diagnosis of a small bowel, pancreas, or colon/rectum neuroendocrine tumor (NET) and underwent R0 resection of the primary tumor, and synchronous metastases, if present, were included in this analysis.

Relationship between metabolic toxicity and efficacy of everolimus in patients with neuroendocrine tumors: A pooled analysis from the randomized, phase 3 RADIANT-3 and RADIANT-4 trials.

Background: Hyperglycemia and hypercholesterolemia are class effects of mammalian target of rapamycin inhibitors such as everolimus. This post hoc pooled analysis assessed the potential impact of these events on the efficacy of everolimus.

Methods: Patients with advanced, low- or intermediate-grade pancreatic, gastrointestinal, or lung neuroendocrine tumors received either oral everolimus at 10 mg/d or a placebo in the RAD001 in Advanced Neuroendocrine Tumors 3 (RADIANT-3) and RAD001 in Advanced Neuroendocrine Tumors 4 (RADIANT-4) trials.

Symptom Diaries of Patients with Midgut Neuroendocrine Tumors Treated with Lu-DOTATATE.

We report the impact of Lu DOTATATE treatment on abdominal pain, diarrhea, and flushing, symptoms that patients with advanced midgut neuroendocrine tumors (NETs) often find burdensome. All patients enrolled in the international randomized phase 3 Neuroendocrine Tumors Therapy (NETTER-1) trial (Lu-DOTATATE plus standard-dose octreotide long-acting repeatable [LAR], = 117; high-dose octreotide LAR, = 114) were asked to record the occurrence of predefined symptoms in a daily diary. Change from baseline in symptom scores (mean number of days with a symptom) was analyzed using a mixed model for repeated measures.

Multicohort Retrospective Validation of a Predictive Biomarker for Topoisomerase I Inhibitors.

Purpose: The camptothecin (CPT) analogs topotecan and irinotecan specifically target topoisomerase I (topoI) and are used to treat colorectal, gastric, and pancreatic cancer. Response rate for this class of drug varies from 10% to 30%, and there is no predictive biomarker for patient stratification by response. On the basis of our understanding of CPT drug resistance mechanisms, we developed an immunohistochemistry-based predictive test, P-topoI-Dx, to stratify the patient population into those who did and did not experience a response.

Markers of Systemic Inflammation in Neuroendocrine Tumors: A Pooled Analysis of the RADIANT-3 and RADIANT-4 Studies.

Objective: The aim of the study was to assess the impact of systemic markers of inflammation on the outcomes in patients with neuroendocrine tumors (NETs) treated with everolimus or placebo (as measured by baseline neutrophil-to-lymphocyte ratio [NLR] and lymphocyte-to-monocyte ratio [LMR]).

Methods: Patient data (gastrointestinal, pancreatic, and lung NETs) from 2 large phase 3 studies, RADIANT-3 (n = 410) and RADIANT-4 (n = 302), were pooled and analyzed. The primary end point was centrally assessed progression-free survival (PFS) as estimated by the Kaplan-Meier method.

Molecular Characterization and Therapeutic Targeting of Colorectal Cancers Harboring Receptor Tyrosine Kinase Fusions.

Purpose: Receptor tyrosine kinase fusions in colorectal cancers are rare, but potentially therapeutically relevant. We describe clinical, molecular, and pathologic attributes of RTK fusion-associated colorectal cancer.

Experimental Design: We identified all cases with RTK fusions in patients with colorectal cancer seen at Dana-Farber Cancer Institute (Boston, MA) who underwent OncoPanel testing between 2013 and 2018.

Updated Efficacy and Safety Outcomes for Patients with Well-Differentiated Pancreatic Neuroendocrine Tumors Treated with Sunitinib.

Background: Sunitinib prolonged progression-free survival (PFS) versus placebo in patients with metastatic pancreatic neuroendocrine tumors (panNETs) in a phase III trial. The efficacy and safety of sunitinib in patients with panNETs were confirmed in an open-label phase IV trial.

Objective: To assess the clinical benefit with sunitinib using the combined data from these trials.

Cancer stage at presentation for incarcerated patients at a single urban tertiary care center.

Patients who are incarcerated are a vulnerable patient population and may suffer from less access to routine cancer screenings compared to their non-incarcerated counterparts. Therefore, a thorough evaluation of potential differences in cancer diagnosis staging is needed. We sought to examine whether there are differences in cancer stage at initial diagnosis between non-incarcerated and incarcerated patients by pursuing a retrospective chart review from 2010-2017 for all patients who were newly diagnosed with cancer at an urban safety net hospital.