Aman Chauhan

ASCO Guidelines provide recommendations with comprehensive review and analyses of the relevant literature for each recommendation, following the guideline development process as outlined in the ASCO Guidelines Methodology Manual . ASCO Guidelines follow the ASCO Conflict of Interest Policy for Clinical Practice Guidelines . Clinical Practice Guidelines and other guidance (“Guidance”) provided by ASCO is not a comprehensive or definitive guide to treatment options. It is intended for voluntary use by clinicians and should be used in conjunction with independent professional judgment. Guidance may not be applicable to all patients, interventions, diseases or stages of diseases. Guidance is based on review and analysis of relevant literature and is not intended as a statement of the standard of care. ASCO does not endorse third-party drugs, devices, services, or therapies and assumes no responsibility for any harm arising from or related to the use of this information. See complete disclaimer in Appendix 1 and 2 (online only) for more. PURPOSE: To develop a clinical practice guideline and recommendations for symptom management of patients with well-differentiated grade 1 to grade 3 metastatic gastroenteropancreatic neuroendocrine tumors. METHODS: ASCO convened an Expert Panel to develop a clinical practice guideline by reviewing the literature for relevant guidelines, systematic reviews, randomized controlled trials (RCTs), and observational studies to develop recommendations for clinical practice. RESULTS: The literature review identified eight guidelines, 19 systematic reviews, and three RCTs that informed the development of guideline recommendations. RECOMMENDATIONS: Recommendations are included for carcinoid syndrome, carcinoid heart disease and carcinoid crisis, and functional pancreatic neuroendocrine tumor syndromes. Recommendations are provided for surgical management, liver-directed therapy, and systemic therapy options, as well as palliative care. Limited guidance is provided for sequencing of interventions. Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines .

A phase 2 clinical trial of an innovative yttrium‐90 (⁹⁰Y)/P‐cadherin–directed radioimmunotherapy reinvigorates the notion of tumor‐directed delivery of a therapeutic radioactive payload against ovarian and other solid tumor cancers. New insights in radiobiology and radiopharmacy have repositioned radioimmunotherapy to the cutting edge of personalized medicine oncology treatment.

PURPOSE: To develop recommendations for systemic therapy for well-differentiated grade 1 (G1) to grade 3 (G3) metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs). METHODS: ASCO convened an Expert Panel to conduct a systematic review of relevant studies and develop recommendations for clinical practice. RESULTS: Eight randomized controlled trials met the inclusion criteria for the systematic review. RECOMMENDATIONS: Somatostatin analogs (SSAs) are recommended as first-line systemic therapy for most patients with G1-grade 2 (G2) metastatic well-differentiated GI-NETs. Observation is an option for patients with low-volume or slow-growing disease without symptoms. After progression on SSAs, peptide receptor radionuclide therapy (PRRT) is recommended as systematic therapy for patients with somatostatin receptor (SSTR)–positive tumors. Everolimus is an alternative second-line therapy, particularly in nonfunctioning NETs and patients with SSTR-negative tumors. SSAs are standard first-line therapy for SSTR-positive pancreatic (pan)NETs. Rarely, observation may be appropriate for asymptomatic patients until progression. Second-line systemic options for panNETs include PRRT (for SSTR-positive tumors), cytotoxic chemotherapy, everolimus, or sunitinib. For SSTR-negative tumors, first-line therapy options are chemotherapy, everolimus, or sunitinib. There are insufficient data to recommend particular sequencing of therapies. Patients with G1-G2 high-volume disease, relatively high Ki-67 index, and/or symptoms related to tumor growth may benefit from early cytotoxic chemotherapy. For G3 GEP-NETs, systemic options for G1-G2 may be considered, although cytotoxic chemotherapy is likely the most effective option for patients with tumor-related symptoms, and SSAs are relatively ineffective. Qualifying statements are provided to assist with treatment choice. Multidisciplinary team management is recommended, along with shared decision making with patients, incorporating their values and preferences, potential benefits and harms, and other characteristics and circumstances, such as comorbidities, performance status, geographic location, and access to care. Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines .

Background Large cell neuroendocrine carcinoma (LCNEC) of the lung is a rare, aggressive cancer most commonly found in the lungs but not exclusively, with a worse prognosis than non-small cell lung carcinomas. Currently, LCNEC patients are treated using small cell and non-small cell protocols. This study aims to use the SEER database to identify demographic, clinical, pathological, and therapeutic factors affecting the prognosis and survival of patients with LCNEC of the lung. Methods Demographic, clinical, and management data of patients with lung LCNEC were extracted from the SEER database for the period 2000–2018. Results In the USA, LCNEC has a higher incidence in elderly white men: M:F ratio = 1.2:1, Caucasian: 83.3%, mean age: 67 ± 10.2 years. The most common treatment modality was chemotherapy only: 29.2%, followed by surgery: 21.5% (but in this group the statuses of chemotherapy were unknown), and combination surgery/chemotherapy: 8.8%. The overall and cause-specific 5-year survival was 17.5% (95% CI 16.3–18.8) and 21.9% (95% CI 20.5–23.4), respectively. By treatment, the best 5-year survival was for surgery alone (48%), followed by multimodality therapy (chemo + surgery + radiation) at 35% (95% CI 27–43). Age > 60 years, male gender, size > 7 cm, and nodal and liver metastasis were independent risk factors associated with increased mortality. Conclusion Lung LCNEC is an aggressive neoplasm most common in older white males that presents at an advanced stage despite small primary tumors. Most patients die within 2 years. The best predictor of survival is surgery with chemotherapy. Given its dismal prognosis, new treatment guidelines are needed for this aggressive cancer.

Neuroendocrine tumor (NET) incidence has grown. The treatment landscape for advanced NETs is rapidly evolving, but there are limited head-to-head data to guide treatment sequencing decisions. We assessed the available clinical data to aid practicing clinicians in their routine clinical decision-making. Clinical trials have demonstrated efficacy benefits for new therapies in advanced NETs. Emerging long-term data from these trials have enabled clinicians to make more accurate risk-benefit assessments, particularly for patients receiving multiple lines of therapy. However, clinical data specifically regarding treatment sequencing are limited. In lieu of definitive data, treatment sequencing should be based on disease-related factors (e.g., site of tumor origin, volume of disease) and patient-related characteristics (e.g., comorbidities, patient preferences). Clinical decision-making in advanced NETs remains highly individualized and complex; important evidence gaps regarding treatment sequencing remain. Given this, advanced NET management should be a joint effort of multidisciplinary teams at referring and high-volume centers. Additional clinical trial and real-world evidence are needed to meet the challenge of understanding how to sequence available NET therapies. Until these trials are conducted, the best practices provided in this review may serve as a guide for clinicians making treatment sequencing decisions based on the available data.

Neuroendocrine neoplasms (NENs) encompass a variety of neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs) which can arise anywhere in the body. While relatively rare in the pediatric population, the incidence of NENs has increased in the past few decades. These neoplasms can be devastating if not diagnosed and treated early, however, symptoms are variable and can be indolent for many years. There is a reported median of 10 years from the appearance of the first symptoms to time of diagnosis. Considering some of these neoplasms have a mortality rate as high as 90%, it is crucial healthcare providers are aware of NENs and remain vigilant. With better provider education and easily accessible resources for information about these neoplasms, awareness can be improved leading to earlier disease recognition and diagnosis. This manuscript aims to provide an overview of both the most common NENs as well as the rarer NENs with high lethality in the pediatric population. This review provides up to date evidence and recommendations, encompassing recent changes in classification and advances in treatment modalities, including recently completed and ongoing clinical trials.

Oncolytic viruses have made a significant inroad in cancer drug development. Numerous clinical trials are currently investigating oncolytic viruses both as single agents or in combination with various immunomodulators. Oncolytic viruses (OV) are an integral pillar of immuno-oncology and hold potential for not only delivering durable anti-tumor responses but also converting “cold” tumors to “hot” tumors. In this review we will discuss one such promising oncolytic virus called Seneca Valley Virus (SVV-001) and its therapeutic implications. SVV development has seen seismic evolution over the past decade and now boasts of being the only OV with a practically applicable biomarker for viral tropism. We discuss relevant preclinical and clinical data involving SVV and how bio-selecting for TEM8/ANTXR1, a negative tumor prognosticator can lead to first of its kind biomarker driven oncolytic viral cancer therapy.

Somatostatin receptors (SSTR) are expressed in various neoplasms and can be targeted for both diagnostics as well as therapeutics. This systematic review aims to compile and discuss the prevalence of somatostatin receptor expression in various neoplasms. We performed a literature search from Google Scholar and PubMed using relevant keywords to look for all publicly available data regarding SSTR expression in various cancers. Both histopathological and radiographical studies were included for SSTR assessment. We found that many cancers express SSTR with varying prevalence. SSTR is now a well-established theranostics biomarker. We now have highly sensitive and specific diagnostic modalities like gallium 68 DOTATATE and copper 64 DOTATATE scans to screen for SSTR-2 and then target it therapeutically with lutetium 177 DOTATATE. A thorough understanding of SSTR expression in other tumors will open the channels for exploring potential SSTR targeting.

Opinion statement The classification of mixed neuroendocrine-non-neuroendocrine neoplasms (MiNEN) is evolving, and no clear management guidelines are currently available. However, recent studies provide insight into factors affecting outcomes and could help develop treatment decisions for patients with these rare malignancies. The majority of MiNENs have a poorly differentiated neuroendocrine carcinoma (NEC) component which is associated with an aggressive clinical course and poor outcomes. Due to the paucity of clinical trials, strategies adopted in gastrointestinal cancers and NECs are used to manage MiNENs. It is also to be noted that the thoracic neuroendocrine neoplasm WHO 2021 classification does not recognize MiNEN terminology but suggests an equivalent terminology called “combined neuroendocrine non neuroendocrine neoplasm.” Surgical management is appropriate in early-stage disease with a low threshold for addition of adjuvant chemotherapy. Multimodality treatment with chemotherapy offers a survival benefit in advanced disease or when surgical resection is not possible without significant morbidity. Chemotherapy should be directed at the more aggressive component which is often the NEC component. In addition, molecular testing should be employed to evaluate patients for enrollment in clinical trials and other targeted treatments. Being a rare disease with retrospective studies and case series providing the majority of data on treatment selection, it is essential to include more granular details of pathology (e.g., Ki-67, mitotic index, percentage of each component, staging information) and treatment modalities (e.g., type and duration, rationale, radiologic response, survival outcomes) in future studies to make systematic reviews possible and help derive meaningful conclusions.

Bronchopulmonary neuroendocrine tumors (BPNETs) are the second most common subset of NETs after gastroenteropancreatic NETs. Historically, most clinical studies have excluded BPNETs during drug development and the data is often extrapolated from non-BPNETs. However, growing burden of BPNETs and the development of novel treatment strategies including targeted therapies and radiopharmaceuticals have paved the way for revisiting treatment strategies. In this review, we go over recent advances in the management of BPNETs and summarize consensus guidelines with the help of research data and clinical scenarios.