Dillon, Joseph S.

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.

632 Background: Paltusotine is an oral, nonpeptide, selective somatostatin receptor 2 agonist. In a phase 2 study, treatment with once-daily paltusotine reduced the frequency and severity of carcinoid syndrome (CS) symptoms and was well tolerated. The effect of paltusotine on biomarkers of serotonin and 5-hydroxyindoleacetic acid (5-HIAA) was further explored. Methods: This exploratory study, without formal power calculations, included an 8-week randomized treatment phase (completed) and a 102-week open-label extension phase (currently ongoing). The purpose was to evaluate safety, pharmacokinetics, and exploratory efficacy endpoints, including changes in biomarkers of paltusotine treatment. Enrolled patients were adults with a stable, documented grade 1 or 2 neuroendocrine tumor (NET) and CS. These patients were actively symptomatic and either untreated with somatostatin receptor ligand (SRL) therapy (average of ≥4 bowel movements [BMs] per day or >2 flushing episodes per day in ≥2 days over a 2-week period) or washed out of SRL therapy (symptoms previously controlled on SRL), with demonstrated symptom worsening after washout. Patients were randomized to once-daily paltusotine 40 mg or 80 mg; one optional uptitration (from 40 mg to 80 mg or 80 mg to 120 mg) was permitted. Blood samples for assessment of biomarkers (serum serotonin and plasma 5-HIAA) were collected longitudinally from screening to end of treatment. Upper limit of normal was prespecified as 541 ng/mL for serotonin and 22 ng/mL for 5-HIAA. This analysis focuses on changes in biomarker from baseline to the end of 8-week randomized treatment phase and after approximately one year (48 weeks). Results: Thirty-six patients (n=9 untreated; n=27 SRL washout) were randomized. Mean age was 60.8 years (range 35-83), and 52.8% were female. Nineteen patients had grade 1 NETs, and 17 had grade 2 NETs. As reported previously, treatment with once-daily, oral paltusotine was well tolerated and reduced the frequency and severity of CS symptoms, justifying further clinical development of the 80 mg dose. Mean serum serotonin decreased from 1553.0 ng/mL at baseline to 643.9 ng/mL at Week 8, and mean plasma 5-HIAA decreased from 245.1 ng/mL to 159.7 ng/mL. There was a trend of untreated patients achieving a greater reduction in comparison to washout patients. At 48-week follow-up, mean serum serotonin was stabilized at 791.50 ng/mL (n=20), and mean plasma 5-HIAA was stabilized at 190.45 ng/mL (n=20). Conclusions: Paltusotine significantly reduced serotonin and 5-HIAA levels, with effects maintained at 48 weeks. Biomarker reductions paralleled reductions in BM and flushing frequency. These findings support further investigation in the ongoing phase 3 study (CAREFNDR, NCT07087054). Clinical trial information: NCT05361668 .

AbstractNeuroendocrine neoplasms (NENs) with peritoneal metastases (PM) represent a complex clinical challenge because of low incidence and heterogeneous phenotypes. This commentary describes the results of a national consensus aimed at addressing clinical management of patients with NENs and PM. An update of the 2018 Chicago consensus guidelines was conducted with a modified Delphi technique, which encompassed two rounds of voting. The levels of agreement for various pathway blocks were assessed, and key systemic therapy concepts were summarized by content experts. Supporting evidence was evaluated via a rapid literature review. Overall, the level of evidence for the management of PM in this disease was universally low. In total, 107 participants responded in the first round, with 88 of 107 (82%) participating in the second round. Strong consensus (>90%) was achieved in five of seven (71%) and seven of seven (100%) blocks in rounds 1 and 2, respectively. A multidisciplinary approach including psychosocial and wellness assessments received a strong positive recommendation. Management of NENs with PM was organized according to disease grade and symptom profiles. In grade 1 and 2 well‐differentiated NENs, cytoreductive surgery received strong support (>95%) after the management of functional syndromes (if present). For grade 3 well‐differentiated NENs, systemic therapy is the primary recommendation, with surgical resection considered in select cases. Given the limited evidence, the consensus‐driven clinical pathway offers vital clinical guidance for the management of NENs with PM. The need for high‐quality evidence remains critical to the field.