Benjamin Chevalier

What is the prevalence and risk of skeletal-related events (SREs) in patients with NETs and bone metastases? We all realize that the prevalence of bone mets is much higher in the PET era than it was thought to be in the Octreoscan era owing to the much better sensitivity of SSTR PETs. What is not as well known is the clinical relevance of bone mets. This study adds to that literature and provides a novel risk score for predicting SREs. A few key findings below: -- 400 patients, most were asymptomatic (64%), had sclerotic lesions (77%), Krenning 4 (71%), and had >3 sites (69%) of osseous disease -- A high proportion of patients had osseous metastases at sites with high risk for fracture, including vertebra (82%), pelvis (63%), and peri-trochanteric femur (34%). -- 13% in the entire cohort suffered a fracture -- Fracture prevalence was significantly lower in small bowel neuroendocrine tumors (NETs, 7%) and Grades 1 and 2 disease (8% and 9%, respectively), with higher prevalence in pancreatic NETs, paragangliomas/pheochromocytomas, lung carcinoid, and Grade 3 disease (≥20% for each; p-values <.05) -- Prevalence of osseous metastatic disease approximates 20% in well-differentiated NENs A different question, yet to be addressed well, is the activity of bone-protecting agents in this population but if we are designing a trial, this risk score sure could be applied. Excellent work led by Jason Starr at Mayo Clinic Florida. @sonbol_bassam @PatrickMcGarrah @Meddoc77 @TubaKendi @TuckerCoston onlinelibrary.wiley.com/doi/…

It sure looks like well diff G3 lung NETs are a thing... In this study, 28 such cases, all well-differentiated and all RB1/TP53 wild type had worse overall survival and recurrence free survival.

MEN1 - Association between genotype and clinical behavior of duodenopancreatic NETs. An excellent study led by @OmairShariq evaluating 153 patients with MEN1 and the risk of re-intervention following resection according to genotype. Truncating mutations predict higher risk of metastases and reinterventions. Notably, small NETs, ≤2 cm, can metastasize. Key findings: -- Among 153 patients with multiple endocrine neoplasia type 1, 94 (61%) underwent surgical resection for duodenal and pancreatic neuroendocrine tumors at a median age of 40 (interquartile range, 28–49) years -- After a median follow-up of 16.4 years, 25 patients (27%) required reintervention, with 45 total procedures performed -- Truncating multiple endocrine neoplasia type 1 variants were significantly more common among patients undergoing reintervention (88.0% vs 63.8%; P = .024). --Truncating genotype was independently associated with reintervention (hazard ratio, 3.82; 95% confidence interval, 1.25–16.68; P = .036). --Among 84 patients without metastases at surgery, 24 (28.6%) developed distant metastases during follow-up --Truncating genotype independently predicted shorter distant metastasis-free survival (hazard ratio, 5.55; 95% confidence interval, 1.56–35.40; P = .024). --37.5% of patients who developed metastases had a largest resected tumor ≤2 cm. @MayoCancerCare sciencedirect.com/science/ar…

This is a fascinating but dense paper on molecular profiling of lung NENs. A few take-home points: -- There arefour strikingly different molecular groups that vary in patient characteristics, genomic and transcriptomic profiles, microenvironment, and morphology. -- A new molecular group, enriched for highly aggressive supra‐carcinoids that displayed an immune‐rich microenvironment linked to tumour-macrophage crosstal -- There appears to be an undifferentiated cell population within supra-carcinoids showing the transcriptomic similarities between supra-carcinoids and the recently identified atypical small cell lung cancer tumours, further demonstrating their molecular link to high-grade lung neuroendocrine carcinomas -- There appear to be distinct evolutionary trajectories, suggesting that molecular groups are determined early in tumourigenesis by genomic events, and that transitions between groups, though infrequent, are possible for supra-carcinoids link.springer.com/article/10…

Are you interested in knowing the outcomes of the different subgroups participating in the NETTER-2 trial of PRRT with Lu-177 DOTATATE vs. octreotide LAR? If so, wait no longer. It is available online now. In short, PRRT is effective in this population. -- PFS in G2: 29 months -- PFS in G3: 22.2 months -- PFS in pNETs: 19.4 months -- PFS in sbNETs: Not reached Response rates are quite high: -- G2: 40.4% -- G3: 48.1% -- pNETs: 51.2% -- GI/sbNETs: 33.3% More details below... thelancet.com/journals/eclin…

Are you interested in knowing more about the hematological consequences of radiopharmaceutical therapy (radioligand therapy) in patients with neuroendocrine tumors and prostate cancer? If so, we have the right article for you... @MrinalPatnaik @Yael_Kusne @sonbol_bassam @WallaceKleinS jnm.snmjournals.org/content/…

It's out in print! The COMPETE phase III trial of patients with GEPNETs. Mostly (83-86%) pre-treated patients with GEPNETs (pancreas 57-58%, small bowel (24-26%). 2:1 randomization to 177Lu-DOTATOC vs. everolimus. The primary endpoint, PFS, strongly favors Lu-177 DOTATOC, 23.9 vs. 14.1 months. No difference in OS but data not mature and as always, it is difficult to evaluate OS as many patients will ultimately get PRRT outside of a trial. Therefore, OS is not a suitable endpoint for NET trials. This is very important new data on sequencing of systemic therapy beyond first line. No new safety signals. Bravo to the COMPETE team including @Ja_Capdevila @GCarboneroLab @JHernando3 @drdelolmo_mbel sciencedirect.com/science/ar…

Non-ASCO oncology news... The randomized, noncomparative OCLURANDOM trial of Lu-177 DOTATATE vs. sunitinib is now out. As can be seen, the primary endpoint, PFS at 12 months, was 81% vs. 42% with sunitinib, the control arm. The ORR was 63% in the patients receiving PRRT, higher than seen in other studies and the ORR in the patients receiving sunitinib was 30%, much higher than the 9% seen in the NEJM 2011 trial. This is a valuable addition to the literature but the trial design, randomized but noncomparative, needs to be kept in mind when comparing the arms. sciencedirect.com/science/ar…