🦓 💯KEY HIGHLIGHTS from Dr Singh's talk on NET year in review: 💊 Therapeutics: - COMPETE trial- Lu177-Edotreotide with superior PFS compared to everolimus in GEPNETs @Ja_Capdevila -OCLURANDOM- Luthathera with improvement in response rate and PFS compared to sunitinib in pNETs (both showing PRRT better than targeted therapies- should be sequenced before targeted therapies) -CABINET- published in NEJM and cabozantinib approved for progressive NETs. New QoL data- no deterioration. -ALPHAMEDIX02-Phase 2 Pb212-DOTAMTATE active in RLT naive and RLT-exposed NETs. RLT-naive- ORR 60% and 36 month PFS 72%. RLT-exposed ORR 34%, 18-month PFS-83%. Concern for dysphagia!! Concern for renal toxicity as well. -Pb212-VMT alpha NET: Early data- promising ORR (35%) and no major AEs. Especially no dysphagia. #ESMO25 @OncoThor -RETNET trial- Chemo vs bland embolization- similar for hepatic PFS and extra-hepatic PFS. Carcinoid symptom control similar, more AEs with bland. -LITESPARK-015 (@Ja_Capdevila)- belzutifan in pNETs- ORR 10%, mPFS 3.9 months. gVHL --> durable responses (already FDA approved)- perhaps limit use to only these patients for now. - STARTER NET- everolimus vs lanreotide+everolimus. Results quite puzzling- not practice changing, control arm not appropriate per NA standards. - Pazopanib in extrapancreatic NETs- Bergsland et al. signal of activity but high AEs. Limited clinical relevance. - Lu177 DOTATATE- in advanced pheo/para (JCO 2025)- Phase II- mPFS 19.9 months, 17% catecholamine release syndrome. SDHx- benefit relatively lesser. - Cabo+atezo: open label phase 2. 6 cohorts across sites of origin. (@Ja_Capdevila et al) ORR 16.7% in GEP-NETs. Not practice changing for now. - CTLA4 and PD-1 (DART) in pNETs- JITC 2025- some responses, but overall benefit limited. - AveNEC trial- another negative study, demonstrating limited role of ICI in extra-pulm NENs. -LBL-024 (4-1BB, PD-L1) in combination with EP in NECs- ORR 75%, DCR 92.3%. ASCO 25. - Obrixtamig in extra-pulmonary NEC (epNEC) by @Ja_Capdevila et al- ORR 40% in DLL3-high, only 3% in DLL3-low. Promising results for DLL3-high. -NORDIC NEC2 study- ORR 30%. 20-40% immediate progression. Poor PS, Ki67 >55%, female sex: worse outcomes. Labor of love by Sorbye et al. 🔪 Surgery: -Partelli et al- borderline resectable pNETs- Tumors>3 cm, Ki67>5%, tumor VTE- poorer outcomes. - Moonen et al, Modern Pathology 2025- Dutch registry. IHC risk stratification panel predicting outcomes with resection of lung NETs. - Tslimigras et al ASO 2025- mesoappendiceal invasion does not predict benefit of hemicolectomy in appendiceal neoplasms. - Dumas et al ASO 2025- Metastatic NETs- ?surgery better than liver directed therapy for liver metastases?- more AEs with embolization. 🚀Other: - Chan et al. JNM 2025- MTV (metabolic tumor volume) on FDG PET- predicts outcomes and SUVmax does not. - BEND2 fusions- predictor of outcomes in pNETs. Wood Trageser et al Modern Pathology 2025. - DLL3 data- expression across sites of origin, include WD G3. @rohit_thum et al (in press) pre-print on med Rxiv 2025. - Gudmundsdottir et al @MayoClinic - regardless of Ki67- ALT+ resected WD pNETs did worse. ALT may be included in risk models? J Neuroendocrinol 2025 -Patte et al. SBNETs 4 molecular subtypes (vesicular, epithelial, immune and mesenchymal)!! @Nature Communications 2025 -Ji et al. Cancer Cell 2025- proteomic subtypes of non functional pNETs. -Sukrithan et al- WGS in NENs- JNCCN 2025- high prevalence of P/LP alterations. Guidelines: - ASCO symptom management: JCO Oncol Practice 2025 -MEN1 guideline- Lancet Endocrinol 2025 #NANETS25 @helops79 @NVijayvergiaMD @AmanChauhanMD @HalletJulie @SethConcorsMD @ChandrikhaC @spartelli @GIMedOnc @TheGutOncLab @PoHienEar @DraMartinezLago