Mailman, Josh

Abstract Background Neuroendocrine tumors (NETs) are rare, heterogeneous neoplasms associated with prolonged survival and substantial symptom burden. However, patient-reported outcomes across NET subtypes remain poorly characterized, particularly in real-world settings. This study describes baseline health-related quality of life (HRQoL) and care experiences among patients with gastroenteropancreatic and lung NETs, examining differences by tumor site and time since diagnosis. Methods The Neuroendocrine Tumors–Patient Reported Outcomes study is a prospective, multi-institutional US cohort of adults (aged 18 years and older) with incident small intestinal, pancreatic, gastroenteropancreatic, or lung NETs diagnosed from January 2018 through September 2024, identified via a validated electronic medical record–based computable phenotype. Baseline surveys assessed HRQoL, symptoms, care experiences, and clinical characteristics using validated instruments. Descriptive statistics and standardized mean differences compared responses by NET site and time since diagnosis. Results Among 2367 participants (mean age = 57.8 years; 57.3% female), 1974 had gastroenteropancreatic NETs (659 small intestinal NET, 555 pancreatic NET) and 393 had lung NETs. Fatigue (mean = 33.0), insomnia (mean = 32.5), and diarrhea (mean = 25.7) were the most burdensome symptoms. Lung NET patients reported worse dyspnea (standardized mean difference = 0.58, P < .001) and lower physical, role, and global QoL scores than those with gastroenteropancreatic NETs, while pancreatic NET patients reported better functioning. Diarrhea worsened over time, especially in small intestinal NETs. Most rated care highly (75.3%) but cited concerns about treatment side effects (80.4%), costs (60.7%), and travel burden (58.8%). Conclusions This large US cohort reveals persistent symptom burden and HRQoL variation by tumor site and disease duration, underscoring the need for longitudinal HRQoL assessment in NET care.

Abstract Introduction: Recruitment for rare disease studies is challenging due to small eligible populations. Traditional clinical research management systems often lack tools to track recruitment contacts prior to enrollment. The NET-PRO study, focused on neuroendocrine tumors (NETs), implemented a participation monitoring system to enhance recruitment efficiency and representativeness. Methods: NET-PRO is a multicenter cohort study of 2538 adults diagnosed with gastroenteropancreatic (GEP) or lung NETs between January 2018 and September 2024. Recruitment occurred from January 2022 to February 2025 across 14 U.S. medical centers. Sites used flexible recruitment methods (email, mail, phone, in-clinic) and tracked contacts using REDCap-based tools. Participant characteristics were analyzed by enrollment mode (online or mail) and recruitment difficulty (number of contacts required prior to enrollment) using standardized mean differences, chi-square tests, and ANOVA. Results: Of 9279 contacted patients, 2675 consented (28.8%) and 2538 enrolled (27.4%). Most enrolled online (83.2%), while 16.8% enrolled by mail. Mail respondents were older, had lower education and income, and more comorbidities. Among those enrolled, recruitment difficulty was associated with older age, lower education and income, but not comorbidity. Over half of the most difficult-to-recruit participants enrolled online. Contact methods varied by attempt, with email dominating early contacts and phone/mail used more in later attempts. Conclusions: A participation monitoring tool supported flexible, multimodal recruitment and improved sample representativeness in a rare cancer study. Tracking recruitment contacts enabled adaptive strategies and may reduce bias in observational research by enabling better outreach to harder-to-reach populations.

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 .

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 .

TPS660 Background: Deeper comprehension of gastroenteropancreatic neuroendocrine tumor (GEP-NET) characteristics has led to development of therapeutic interventions such as targeted radionuclide therapies (TRT). In the prospective, randomized, controlled, open-label, multi-center, Phase III COMPOSE trial, the radiolabeled somatostatin analogue 177Lu-edotreotide will be compared to approved standard of care with everolimus, CAPTEM or FOLFOX in patients with well-differentiated aggressive grade 2 and 3 (Ki-67 index 15−55%), somatostatin receptor positive GEP-NETS. While TRT is advantageous, a key unmet need is to identify additional markers intended to guide patient selection for TRT. This is highly relevant as TRT is a therapy of growing interest likely to be broadly available for patients with variable phenotypes. Profiling analysis as part of COMPOSE plans to analyze the genetic signature of GEP-NETS through full exome sequencing and gene expression analysis of tumor histology and longitudinal blood samples. This analysis may guide detection of pathogenic mutations in NET patients, to potentially inform treatment and surveillance strategies. Methods: Whole exome analysis of tumor-suppressor- and proto-oncogenes included in several pan-cancer panels, upstream and downstream regulators, and novel candidate genes, will be studied. Following patient consent, historical tumor biopsy and blood samples will undergo genetic analysis. Genetic profiling analysis inclusion will not impact trial involvement or disease management. DNA will be assessed to determine the impact of different types of mutations; mRNA will be assessed to confirm and quantify these assumptions and compare gene expression at different treatment phases. Samples will be analyzed in a central pathology laboratory. The aim of this analysis is to develop software that would integrate genetic data with structural and functional imaging, histopathology and phenotype information for implementation into clinical practice. Clinical trial information: NCT04919226 .