If you are a patient with a NET or a family member or a friend or just interested NET, please check this website out.

Standard vs. reduced dose of everolimus for patients with advanced NETs...? A retrospective study of 170 patients from Mayo Clinic and University Hospitals in Cleveland. @sonbol_bassam @Faresjamall @PatrickMcGarrah and others not found on X. Key findings: -- Patients in the reduced-dose cohort were older, with worse PS and more heavily pretreated -- Median OS was shorter in the reduced dose cohort, 43.7 vs. 81.5 months (p=0.02) -- After multivariate adjustment, the difference was no longer statistically significant -- Similarly, the observed difference in PFS (7 vs. 12.4 months), was no longer significant after adjusting -- Almost half of the full-dose starters needed dose reduction Lower doses may be reasonable in patients expected to have poor tolerance but cannot be routinely recommended. A prospective trial (NCT06472388) is ongoing, led by @RachelRiechelm2 onlinelibrary.wiley.com/doi/…

This is a good paper from @DrDavidLChan and team in Sydney. Oligodiscordant (my new fave imaging word) NETs are very real, not uncommon at all, especially lung NETs but also GEPNETs. Radioligand therapy may be of help but of note, the outcomes (OS and PFS) do seem inferior to what has been seen in RCTs previously published (NETTER 1 and 2, COMPETE). If the non-avid component(s) can also be treated effectively, (e.g. embolotherapy, RT, resection...), RLT may not be a bad option. link.springer.com/article/10…

All of us who see patients with rare cancers (which is almost all my practice now...) know that without expert pathologists, we are blind, trying to navigate uncharted waters in the dark without a compass or GPS... Pathologists, just like the rest of us, are not infallible and sometimes get things wrong (we all do...). This very interesting study looks at the challenges in pathological diagnosis of neuroendocrine neoplasms (NENs) and the experience of ENDOCAN-TENpath, the French national expert network for NEN pathology which has monthly virtual "third-reading" sessions for collegial review of difficult cases (what a brilliant concept!). Not surprisingly, diagnoses change after such a review, often with major therapeutic consequences. Here are some of their findings: -- Of 3239 cases received by ENDOCAN-TENpath, 126 (3.9%) were submitted to third-reading by 22 of 33 network pathologists -- Diagnostic difficulties fell into four categories: high-grade NEN classification (33.3%), mixed neuroendocrine/non-neuroendocrine neoplasm diagnosis (36.5%), incomplete neuroendocrine phenotypes (23.0%), and unfamiliar entities (7.1%) -- Consensus or majority diagnosis was reached in 102 cases (81%). Unresolved cases were due to lack of consensus (n = 13) or insufficient material (n = 10) -- Critically, the process yielded decisions with major therapeutic consequences: 20/46 presumed NENs were reclassified as non-neuroendocrine malignancies and 5/25 presumed adenocarcinomas as NENs, fundamentally altering treatment strategy. -- 32/42 ambiguous high-grade NENs were definitively classified as tumor or carcinoma, directly determining first-line chemotherapy regimen. This illustrates the need for expert centers with expert pathologists who are willing to collaborate. I have already seen a few similar cases this year, including a patient treated with chemo for presumed poorly diff duodenal adenocarcinoma which turned out to be lipid-rich grade 2 well diff NET... A very challenging case able to trick even the best pathologists. And naturally, I must tag @IHC_guy on this post... sciencedirect.com/science/ar…

Time for a prospective trial of DLL3-targeting BiTEs in lung NETs. In this small study of 11 patients with mostly what will soon be called G3 lung NETs (finally!), all DLL3+, tarlatamab resulted in ORR of 73% and stability in others. CRS was common but mostly grade 2 or lower. I am ready for a trial and I know many of the patients I see are as well... sciencedirect.com/science/ar…

The classification of lung NETs is moving closer to the one for NETs below the diaphragm. Well diff grade 3 NETs (G3 NETs) of the lung will be introduced and they really seem to be a thing... (see link in comments with the IASLC updates). In this small study (small in terms of G3 lung NETs - all p53 wt, Rb1 retained), they seem to have a different prognosis. As always, more work is needed including on optimal therapy and more... sciencedirect.com/science/ar…

This is the best paper you will read on nuclear imaging in patients with NETs this summer. Trust me! onlinelibrary.wiley.com/doi/… @ENETS_ORG @deroose_c @HansHofland1 @DrAngelaLamarca This is the table I always needed for myself and for teaching...

And if you want to learn more between World Cup soccer games today, may I direct you to this excellent new review on the topic of lung NETs...? academic.oup.com/edrv/articl…

I have been scratching my head over a challenging clinical scenario lately. I needed help as I often do and I am never afraid to ask, be it a colleague or AI... I ran de-identified IHC and genomics data through OpenEvidence and ChatGPT institutional versions. Both provided useful info, and both performed very similarly and were given identical prompts. Once you have the basic knowledge and understanding, and know how to ask questions, AI is a powerful tool indeed. A patient in the 70s, 40 pack year h/o smoking, quit 15 years ago. A widely disseminated malignancy with a dominant right lung mass. Metastases throughout the lungs, skin, kidney (why don't we see that more - all the blood goes through there thousands of times daily...?). Initial biopsies consistent with neuroendocrine carcinoma or a carcinoma with neuroendocrine differentiation. Not clearly poorly diff but not typical for well diff either. Biopsies from the lung mass and thyroid show the same. Focal calcitonin positivity and mildly elevated calcitonin raised concerns for medullary thyroid carcinoma but the presentation is not so fitting for that. IHC signature: -- Pos: CK7, CK AE1/AE3, INSM1, synaptophysin, chromogranin, TTF 1 (SPT4), focally pos for TTF1 (8G7G), PAX8, calcitonin (patchy) -- Neg: p40, POU2F3, GATA3, p63, CDX2, and SSTR2 -- Intact Rb1, wild-type p53 IHC Ki67 16% Liquid biopsy (Tempus xF+): Mutations in EIF1AX and DNMT3A (solid tumor seq pending). My hypothesis is a lung NET (yes, they are lung NETs now) with aberrant calcitonin expression and mild calcitonin secretion) but up to 10% of lung NETs have EIF1AX mutations and you also have to go by the clinical presentation. Calcitonin expression/secretion is also well known (panc NETs can do it too). Both AI models concur that this is most likely lung NET and both provided great rationale for their conclusion but as always, I like the OE format better. I see such potential for the use of AI in management of cancer patients but I also wonder how effective of a tool it is in the hands of the unprepared and unexperienced in the clinic. Time will tell, I guess... Maybe I should have called upon @natasharekhtman or @AnjaRodenMD now that they and their esteemed colleagues published such a fantastic paper recently on lung NETs - sciencedirect.com/science/ar…

Twice today already at ASCO I have heard presenters say “patients failed treatment”. Can we please, please stop that? Treatments fail patients, not the other way around…

Images from the NET clinic... Working in the NET clinic is often humbling... Tumors do not read textbooks and sometimes, things just do not make sense but yet are happening right in front of you. As I often say, every patient with NET is unique (of course, every patient with cancer regardless of cancer type is unique...) with their own clinical presentation. This patient below has metastatic lung NET, indolent, producing very large amounts of serotonin but with no diarrhea or flushing (serotonin does not cause flushing by the way but does cause diarrhea) so essentially asymptomatic in terms of typical carcinoid syndrome. This patient however has carcinoid heart disease with severe tricuspid and pulmonary valve regurgitation. Interestingly, there is no lower extremity edema but there is pulsatile hepatomegaly (a classic finding), both systolic and diastolic murmur, elevated JVP but not a trace of lower extremity edema. Below you can see evidence of hepatic venous congestion in the venous phase of the CT with what sometimes is called nutmeg liver. That lobular pattern is not seen on the arterial phase or on the recent gadoxetate enhanced delayed MRI imaging. I just thought I should share that carcinoid syndrome can present in very atypical ways without the cardinal symptoms of diarrhea and flushing. In this case, carcinoid heart disease is the only manifestation of the syndrome.

Want to know more about the intersection of endocrinology and oncology when it comes to diabetes...? Things like: 1) Glucose control problems with systemic therapy like mTOR inhibitors, ICIs, somatostatin analog and others? 2) Secondary cause of diabetes as an early manifestation of malignant Look no further. @TheLancetEndo has this and much more covered in this excellent review sciencedirect.com/science/ar…

Much welcomed @ENETS_ORG guidance paper on management of patients with lung and thymic NETs (soon we will stop calling them carcinoids...). As always from ENETS, this is quality stuff! If you see patients with this malignancy, you SHOULD read this paper! Thanks ENETS and team including @Ja_Capdevila @deroose_c @GCarboneroLab! onlinelibrary.wiley.com/doi/…

More on treatment related myeloid neoplasms (t-MN) following radioligand therapy (PRRT) in patients with NETs. 4.2% of patients develop t-MN after a median time of 48.3 months. Nine of 13 patients with t-MN received radiosensitizing chemotherapy, almost exclusively capecitabine (not standard practice in the U.S. ). As expected, survival after t-MN and diagnosis was short. 10.4 months. This is a very valuable addition to the literature from @DrDavidLChan and team! pmc.ncbi.nlm.nih.gov/article…