Late result of treatment of neuroendocrine tumor of the pancreas with massive metastatic liver involvement and severe liver failure

Pancreatic neuroendocrine tumors (PNETs) are frequently asymptomatic (in >50% of patients) and are diagnosed at stage IV, typically with synchronous liver metastases. Patients with initially unresectable PNETs presenting with massive liver involvement, systemic intoxication, and multiorgan failure face poor prognosis and often have contraindications to antitumor therapy. We present a clinical case of a female patient followed in St. Petersburg medical institutions since 2009 for multifocal liver lesions initially diagnosed as «hepatic hemangiomatosis». Since January 2016, she has been managed at the A. M. Granov Russian Research Center with diagnosis: PNET G2 T3N1M1 (>80% liver involvement). At initial diagnosis, her condition was graded as severe (ECOG 3) with rapid deterioration due to progressive hepatic failure. The clinical complexity was compounded by contraindications to systemic therapy. The patient received a center-developed treatment algorithm incorporating locoregional approaches. Following treatment, partial response was achieved, allowing treatment-free interval from October 2021 to July 2024, after which systemic therapy was initiated. Currently, the patient is asymptomatic with satisfactory performance status (ECOG 0–1).

1. Strosberg J.R., Weber J.M., Feldman М. et al. Prognostic Validity of the American Joint Committee on Cancer Staging Classification for Midgut Neuroendocrine Tumors // J. Clin. Oncol. 2013. Feb 1; Vol. 31, No. 4. Р. 420–425. doi: 10.1200/JCO.2012.44.5924.

2. Pavel M. et al. Gastroenteropancreatic neuroendocrine neoplasms: ESMO Clinical Practice Guidelines // Ann. Oncol. 2020. Jul; Vol. 31, No. 7. Р. 844–860. doi: 10.1016/j.annonc.2020.03.304.

3. Mayo Clinic, 2022: Shen C., Lopez-Aguiar A.G., Poultsides G. et al. Surgery Versus Intra-arterial Therapy for Neuroendocrine Liver Metastases: A Multicenter International Analysis // Annals of Surgical Oncology. 2022. Vol. 29, No. 2. Р. 953–962. doi: 10.1245/s10434-021-10797-2.

4. Pavel M., Öberg K., Falconi M. et al. ENETS Consensus Guidelines Update for Neuroendocrine Neoplasms of the Pancreas // Neuroendocrinology. 2023. Vol. 113, No. 2. Р. 139–170. doi: 10.1159/000527443.

5. Strosberg J.R., Caplin M.E., Kunz P.L. et al. Final Overall Survival in NETTER-1 Study of 177Lu-Dotatate in Midgut Neuroendocrine Tumors // Journal of Clinical Oncology. 2022. Vol. 40, No. 23. Р. 2595–2605. doi: 10.1200/JCO.21.02707.

6. Sorbye H., Kong G., Grozinsky-Glasberg S. Chemotherapy in NEN G3: A Systematic Review and Meta-Analysis // Endocrine-Related Cancer. 2022. Vol. 29, No. 7. Р. R1–R14. doi: 10.1530/ERC-21-0283.

7. Artamonova E.V., Gorbunova V.A., Delektorskaya V.V. et al. Neuroendocrine neoplasia of the gastrointestinal tract and pancreas. RUSSCO practical recommendations, part 1.1. Malignant tumors, 2024, Vol. 14, No. 3s2, pp. 427–444 (In Russ.).

8. De Mestier L., Zappa M., Hentic O. et al. Liver-directed therapies for metastatic neuroendocrine tumors // Cancers. 2021. Vol. 13, No. 5. Р. 981. doi: 10.3390/cancers13050981.

9. Kulke M.H., Benson A.B., Bergsland E. et al. Neuroendocrine Tumors // J. Natl. Compr. Canc. Netw. 2022. Vol. 20, No. 1. Р. 72–126. doi: 10.6004/jnccn.2022.0004.