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Purpose: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are relatively indolent but can be more aggressive. The current recommendations for the use of serum CgA for GEP-NET patients are equivocal. This study was designed to validate an automated CgA immunofluorescence assay for monitoring disease progression in GEP-NET patients., Patients and Methods: A prospective, multi-center blinded observational study was designed to validate an automated chromogranin A (CgA) immunofluorescence assay for monitoring disease progression in GEP-NET patients. Tumor progression was evaluated with Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 by CT/MRI. An increase ≥ 50% above the prior CgA concentration to a value > 100 ng/mL in the following CgA concentration was considered positive., Results: 153 GEP-NET patients were enrolled. Using the pre-specified cut-off of CgA change for tumor progression, specificity was 93·4% (95%-CI: 90·4%-95·5%, p < 0·001), sensitivity 34·4% (25·6%-44·3%), positive predictive value 57·9% (45·0-69·8), negative predictive value (NPV) 84·3% (80·5-87·6), and area under the curve 0·73 (0·67-0·79)., Conclusions: Changes in serial measurements of serum CgA had a favorable specificity and NPV, making this test a useful adjunct to routine radiographic monitoring.

Background and Objectives: Not all gastric neuroendocrine tumors (GNETs) may be classified into one of the three described clinicopathologic subtypes. The purpose of this study was to better characterize GNET subtypes and associated outcomes., Methods: Patients treated for GNET at our institution (1995-2021) were identified. Pathologic specimens of tumors that could not be classified as type 1, 2, or 3 were further reviewed. GNETs were categorized as proton pump inhibitor (PPI)-associated based on changes in the background gastric mucosa consistent with PPI use. Distant metastasis at presentation (DM) and disease-specific survival (DSS) were evaluated., Results: Among 246 patients, there were 164 (67%) type 1, 5 (2%) type 2, 52 (21%) type 3, and 18 (7%) PPI-associated GNETs. Seven (3%) tumors remained unclassified. DM was more frequent with type 3 GNETs (38%) than type 1 (1%), type 2 (20%), or PPI-associated tumors (11%, p < 0.001). Ten-year DSS rates were 100% for type 1, 53% (95% confidence interval [CI], 38%-75%) for type 3, and 80% (95% CI, 58%-100%) for PPI-associated tumors (p < 0.001). GNET subtype, race, and DM were independently associated with DSS., Conclusions: PPI-associated tumors may represent a distinct GNET subtype with intermediate outcomes. Other factors should also be considered in overall prognosis., (© 2024 Wiley Periodicals LLC.)

Purpose: Appendiceal adenocarcinoma (AA) remains an orphan disease with limited treatment options for patients unable to undergo surgical resection. Evidence supporting the efficacy of combined VEGF and PD-1 inhibition in other tumor types provided a compelling rationale for investigating this combination in AA, where immune checkpoint inhibitors have not been explored previously., Experimental Design: We conducted a prospective, single-arm phase II study evaluating efficacy and safety of atezolizumab in conjunction with bevacizumab (Atezo+Bev) in advanced, unresectable AA., Results: Patients treated with the Atezo+Bev combination had 100% disease control rate (1 partial response, 15 stable disease) with progression-free survival (PFS) of 18.3 months and overall survival not-yet-reached with median duration of follow-up of 40 months. These survival intervals were significantly longer relative to a clinically and molecularly matched synthetic control cohort treated with cytotoxic chemotherapy designed for colorectal cancer (PFS of 4.4 months, P = 0.041)., Conclusions: In light of recent data demonstrating a lack of efficacy of 5-fluorouracil-based chemotherapy, Atezo+Bev is a promising treatment option for patients with low-grade unresectable AA; further study is warranted., Significance: AA remains an orphan disease with limited systemic therapy options for patients who are not candidates for surgical resection. These data suggest activity from combined VEGF and PD-L1 inhibition that warrants further study., (© 2024 The Authors; Published by the American Association for Cancer Research.)

Important progress has been made over the last decade in the classification, imaging, and treatment of neuroendocrine neoplasm (NENs), with several new agents approved for use. Although the treatment options available for patients with well-differentiated neuroendocrine tumors (NETs) have greatly expanded, the rapidly changing landscape has presented several unanswered questions about how best to optimize, sequence, and individualize therapy. Perhaps the most important development over the last decade has been the approval of 177Lu-DOTATATE for treatment of gastroenteropancreatic-NETs, raising questions around optimal sequencing of peptide receptor radionuclide therapy (PRRT) relative to other therapeutic options, the role of re-treatment with PRRT, and whether PRRT can be further optimized through use of dosimetry among other approaches. The NET Task Force of the National Cancer Institute GI Steering Committee convened a clinical trial planning meeting in 2021 with multidisciplinary experts from academia, the federal government, industry, and patient advocates to develop NET clinical trials in the era of PRRT. Key clinical trial recommendations for development included 1) PRRT re-treatment, 2) PRRT and immunotherapy combinations, 3) PRRT and DNA damage repair inhibitor combinations, 4) treatment for liver-dominant disease, 5) treatment for PRRT-resistant disease, and 6) dosimetry-modified PRRT., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Appendiceal neuroendocrine neoplasms are most often diagnosed incidentally during appendectomy. The need for subsequent right hemicolectomy (RHC) is determined based on the risk of regional lymph node (LN) involvement. Tumor size has historically been used as an indicator of this risk, but controversy remains regarding its cut off. Furthermore, the impact of RHC on survival is unclear., Methods: We used the SEER database to identify patients diagnosed with appendiceal neuroendocrine tumors., Results: Of 1731 patients, 38.0% had well-differentiated neuroendocrine tumors (WDNETs), 60.8% had mixed histology tumors (MHTs), and 1.2% had poorly differentiated neuroendocrine carcinomas (PDNECs). In patients with WDNETs and MHTs who had adequate lymphadenectomy, higher rates of LN involvement were noted for tumors size 11-20 mm than ≤10 mm (56.8% vs. 11.6%, p <0.001; 32.9% vs. 10.4%, p =0.004, respectively). The type of surgery did not affect OS in cases with MHTs with LN involvement (HR 1.00; 95% CI, 0.53-1.89; p =0.99). Patients with regionally advanced WDNET showed excellent survival and only 3 patients (out of 118) died from cancer within 10 years., Conclusions: 10 mm appears to be a more appropriate cutoff than 20 mm for predicting LN metastasis in appendiceal NETs. Cases with WDNETs and nodal involvement demonstrate overall excellent prognosis irrespective of type of surgery (i.e. RHC may not improve outcome). In MHTs with LN metastases, survival is markedly worse in spite of RHC. The role of adjuvant therapy should be evaluated in this subset., Competing Interests: CONFLICTS OF INTEREST The authors declare that they have no conflicts of interest.