From the Guidelines
High grade neuroendocrine tumors require prompt multidisciplinary management with treatment depending on tumor location, stage, and differentiation, and first-line therapy typically involves surgical resection when possible, followed by systemic therapy with platinum-based chemotherapy regimens such as cisplatin or carboplatin combined with etoposide for poorly differentiated neuroendocrine carcinomas. The management of high-grade neuroendocrine tumors is complex and requires a comprehensive approach.
Key Considerations
- Tumor location, stage, and differentiation are crucial factors in determining the treatment plan 1.
- Surgical resection is often the first-line treatment when possible, followed by systemic therapy 1.
- Platinum-based chemotherapy regimens, such as cisplatin or carboplatin combined with etoposide, are standard first-line treatments for poorly differentiated neuroendocrine carcinomas 2.
- For advanced disease, combination therapy with everolimus (10mg daily) or sunitinib (37.5mg daily) may be considered, as these therapies have shown efficacy in extending progression-free survival (PFS) in patients with advanced pancreatic NETs 2.
- Somatostatin analogs like octreotide LAR (20-30mg every 4 weeks) or lanreotide (120mg every 4 weeks) can help control hormonal symptoms in functioning tumors 2.
- Peptide receptor radionuclide therapy (PRRT) with lutetium-177 dotatate may benefit patients with somatostatin receptor-positive tumors who have progressed on other therapies 2.
Monitoring and Follow-up
- Regular monitoring with imaging (CT/MRI every 3-6 months) and biomarkers (chromogranin A, specific hormones) is essential to assess treatment response and detect potential progression or recurrence 1.
- The prognosis for high-grade neuroendocrine tumors is generally poor, with median survival often less than 12 months for high-grade poorly differentiated neuroendocrine carcinomas, making early intervention and aggressive treatment crucial 1.
From the Research
Definition and Classification of High-Grade Neuroendocrine Tumors
- High-grade neuroendocrine neoplasms are a rare disease entity, accounting for approximately 10% of all neuroendocrine neoplasms 3
- A distinction is made between well-differentiated high-grade (G3) neuroendocrine tumors and poorly differentiated neuroendocrine carcinomas 3
Management of High-Grade Neuroendocrine Tumors
- For metastatic disease, platinum-based chemotherapy is the backbone of treatment 4
- For localized disease, surgical resection with low morbidity is a reasonable treatment option, particularly in lesions where the possibility of obstruction is high 4
- A multimodality approach with either neoadjuvant or adjuvant therapy is warranted due to the high risk of disease recurrence 4
- Chemoradiation should be considered for locally advanced disease, incorporating a platinum-based regimen when possible 4
Treatment Options for High-Grade Gastroenteropancreatic Neuroendocrine Neoplasms
- Platinum-based chemotherapy (cisplatin/carboplatin + etoposide) is considered the first-line palliative treatment 5
- Etoposide can be administered intravenously or orally, with no significant difference in progression-free survival (PFS) or overall survival (OS) observed between the two routes of administration 5
- Irinotecan and cisplatin can be used as adjuvant chemotherapy for completely resected high-grade pulmonary neuroendocrine carcinoma, with a completion rate of 83% and estimated 3-year overall survival rate of 81% 6
Molecular Landscape and Therapeutic Targets for High-Grade Pancreatic Neuroendocrine Neoplasms
- The molecular landscape of high-grade pancreatic neuroendocrine neoplasms is complex, with mutations in key cancer-related genes, extensive genomic rearrangements, and chromosomal instability 7
- Therapeutic strategies targeting the mammalian target of rapamycin (mTOR) pathway, DNA repair pathways, and epigenetic modifiers are being explored 7
- High programmed cell death ligand 1 (PD-L1) expression in some tumors indicates potential for immunotherapy 7