UKINETS2024 22nd Annual Meeting of the UK and Ireland Neuroendocrine Tumour Society 2024 Poster Presentations (33 abstracts)
Case report: immunotherapy for a well-differentiated rectal neuroendocrine neoplasm
Saiji Nageshwaran 1,2 , Aimee Hayes 1 , Dalvinder Mandair 1 , Reza Mirnezami 3 , TuVinh Luong 3 , Jennifer Watkins 3 , Shaunak Navalkissoor 3 , Christos Toumpanakis 1 , Krista Rombouts 2 , Martyn Caplin 1 & Daniel Krell 1
1Royal Free ENETS Centre of Excellence, London, United Kingdom. 2Institute for Liver and Digestive Health, University College London, London, United Kingdom. 3Royal Free Hospital, London, United Kingdom
Introduction: Metastatic well-differentiated rectal neuroendocrine neoplasms (NENs) are heterogeneous and considered ’immune-cold.’ Standard treatments include somatostatin analogues, peptide receptor radionuclide therapy and chemotherapy. We report a case where a patient responded to third-line immunotherapy, despite the absence of predictive biomarkers.
Case Presentation: A 60-year-old man was referred for colonoscopy following bowel cancer screening. A 3 cm rectal polyp, 5 cm above the dentate line, was identified and biopsied. CT and MRI showed this lesion was associated with mesorectal and para-aortic lymphadenopathy and indeterminate liver lesions. Gallium-68 DOTATATE PET CT showed avidity in the rectal primary and abdomino-pelvic nodes, but not in the liver lesions. FDG PET CT was negative at all sites. The liver lesions were too small to biopsy. An anterior resection with aortic lymphadenectomy confirmed a well-differentiated NET (Grade 2, Ki-67 7%), consistent with hindgut origin (ENETS pT2 N1 V1 L1 Pn1 R1). Three months post-operation, surveillance showed an increase in size and number of the liver lesions. Liver biopsy confirmed a NET G2 with a Ki-67 index of 8%, similar to the operative histology, with MMR proficiency and KRAS, NRAS, BRAF wild-type status. Following completion of 6 cycles of first line FOLFOX chemotherapy, repeat imaging demonstrated progressive liver disease. Symptomatic disease progression in the liver alone was again noted after 4 cycles of second line FOLFIRI. A repeat liver biopsy showed no histological change and dual PET scans remained non-avid. Given the disease’s atypical behaviour and chemotherapy-resistance, the patient was offered participation in a Phase 1 clinical trial but declined. He was subsequently commenced on Ipilimumab/Nivolumab through a compassionate access scheme. Remarkably, he achieved a partial response after two cycles, though developed grade 2 immune-related arthritis. The patient’s cancer (primary and liver metastases) are undergoing multi-omic evaluation to establish reasons for response that may refine the use of such therapies.
Conclusion: Dual checkpoint inhibition may be effective in chemotherapy-refractory patients with well-differentiated rectal NETs who are unlikely to benefit from somatostatin receptor-dependent therapies. This case underscores the potential role of immunotherapy and highlights the need for further multi-omic understanding of NETs to select patients for immunotherapy.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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