Wednesday, September 1, 2021

FDAapproved Belzutifan (Welireg) for the treatment of renal cell carcinoma (RCC), pancreatic neuroendocrine tumors (pNET) and hemangioblastomas (HB) in adult VHL patients. The medication is likely to be available for prescription in September 2021.

 



The VHL-associated cystic lesions are generally asymptomatic and do not require any treatment, unless they are indistinguishable from other cystic tumor types with malignant potential. Because pancreatic NET in VHL disease are non-functioning and have malignant potential, it is of clinical importance to find and diagnose these as early as possible.


Tumor types seen in VHL disease include hemangioblastomas in the CNS and retina, renal cell carcinoma, pheochromocytomas and pancreatic neuroendocrine tumors (NET). During their growth, these tumors impair the function of the primary organs and sometimes metastasize to distant organs, and thus are thought to have malignant potential.


VHL disease, NET, can be locally invasive and can metastasize, resulting in much higher clinical significance. NET occurs in 8%-17% of patients with VHL disease. 


Neuroendocrine neoplasms (NENs) are rare malignancies of the aerodigestive, genitourinary and integumentary systems. Their histologies vary from well-to-moderately differentiated neuroendocrine tumors (NETs) to poorly differentiated neuroendocrine carcinomas (NECs) and their natural history has been described in several publications. Most studies are limited due to the small number of cases, inconsistent follow-up or retrospective nature but it is clear, however, that the incidence of NENs is increasing  and that, at least for certain subtypes, survival might be improving.


NENs show a spectrum of behaviors and this makes their treatment challenging. Some exhibit an indolent, slow growth pattern, while others parallel the more aggressive, rapidly spreading tumors such as small cell lung cancer (SCLC); in between there are neoplasms of intermediate malignant potential. Research so far has identified stage, site of origin  and differentiation as well as proliferative indices (Ki-67, mitotic count) as important prognostic factors and multiple scores have been published, trying to predict survival in metastatic disease or recurrence after curative surgery . In general, well- differentiated tumors progress slowly and surveillance may be the best approach in some cases, whereas poorly differentiated neoplasms require urgent aggressive chemotherapy and are associated with markedly shorter survival. Tumors of small bowel origin tend to have a better prognosis compared to NENs originating in the pancreas. Most medical decisions nowadays consider tumor of origin, staging, but also tumor differentiation and mitotic indices (values that have formed the basis of the current grading system).


While it is generally accepted that stage IV (presence of metastasis) portends a poor prognosis for most neoplasms including NENs, there is no consensus on the gravity and importance of metastatic sites, or how they interplay with the primary tumor site when it comes to survival estimates. 


It has been shown for example that the incidence of certain types of NETs has increased and that the survival of patients has improved over time . This has been partially attributed to treatments such as somatostatin analogues (time to progression prolonged by 8 months), targeted therapies such as everolimus and sunitinib (progression free survival benefit of about 5 months for both), and hopefully pazopanib or peptide receptor radionuclide therapy (PRRT)  in the future. With the latest iteration, the SEER database was enriched to include details of general metastatic sites, including lung, liver, bone and brain. This presents a unique opportunity to study the behavior of metastatic neuroendocrine tumors across a range of sites and histologies. We sought to explore the behavior of NENs with regards to the site of origin and metastatic areas and hypothesized that the site of metastasis will carry different prognostic significance depending on tumor grade and tissue of origin.


It is of clinical importance to find and diagnose pancreatic NET in patients with VHL as early as possible. It is recommended that comprehensive surveillance for abdominal manifestations in VHL patients including pancreatic NET should start from the age of 15. In general, pancreatic NET with or without VHL disease show a slow growth phenotype and patients have a good prognosis. VHL patients at lower metastatic risk from pancreatic NET should be spared the risks of surgical resection.


Lung, liver, bone and brain metastases were observed in and 6% of metastatic patients respectively.


Pancreatic NETs that have not spread outside the pancreas should be completely removed, if possible, because these tumors are more likely to be cured with surgery. Sometimes, however, after the surgeon starts the operation it becomes clear that the cancer has grown too far to be completely taken out. The general metastatic sites, including lung, liver, bone and brain.


Site of metastasis plays an important role for survival in metastatic NEN patients and is probably reflective of variable tumor biology, even among NENs of similar origin and grade.

  • Alex Trebek

  • Steve Jobs

  • John Hurt

  • Alan Rickman

  • Sally Ride

  • She was one of America’s first female astronauts

Not naming the Hollywood actors and actresses but Indian 

  • Irrfan Khan

lost their lives to neuroendocrine tumours.


On August 13, 2021, the US Food and Drug Administration (FDA) approved Belzutifan (Welireg) for the treatment of renal cell carcinoma (RCC), pancreatic neuroendocrine tumors (pNET) and hemangioblastomas (HB) in adult VHL patients. The medication is likely to be available for prescription in September 2021.

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