OpenHealth Q&A

Management Strategies for Neuroendocrine Cancer Recurrence Following Surgical Intervention

Seeking expert medical insights on possible next steps for the following patient case. Next-Generation Sequencing (NGS) failed to identify any distinct markers, and the prior treatment involving neoadjuvant chemotherapy combined with immunotherapy (Cisplatin, Etoposide, and Durvalumab) led to a stabilized tumor, showing no further growth. Would administering Carboplatin, Irinotecan, and Durvalumab in a second-line capacity be an appropriate option? Are there alternative measures available to tackle the metastases present in multiple locations? Thank you! **Patient Profile:** **Age:** 68 years **Diagnosis:** Poorly Differentiated Neuroendocrine Carcinoma of the Gallbladder **Initial Diagnosis Date:** February 2025 # Surgical Background: - **Procedure Performed:** Extended cholecystectomy alongside duodenal and partial bowel resection (ileo-colic anastomosis) - **Surgery Date:** April 2025 - **Surgical Findings:** Gallbladder mass exhibiting infiltration into the liver and adjacent intestinal wall - **Postoperative Pathology (May 2025):** - **Tumor Type:** High-grade NEC with a Ki-67 proliferation index of approximately 55-60% - **Lymph Node Involvement:** ypN1 (1-2 nodes positive) - **Surgical Margins:** Clear - **Staging:** ypT4, ypN1 (AJCC 8th Edition, following treatment) # Immunohistochemistry (IHC) Analysis and Biomarkers: - **Synaptophysin:** Strong, widespread positivity - **Pan-CK:** Patchy positivity observed - **Others (Chromogranin, CK7, CK19, CDX2):** Negative - **INI-1:** Expression remains intact - **Ki-67 Index:** 55-60% - **PD-L1 (FoundationOne):** Tumor Proportion Score (TPS) at 25% - **Mismatch Repair (MMR):** Expression intact (not MSI-high) # Molecular Testing Results (FoundationOne CDx): - **Identified Pathogenic Variants:** TP53 and MYC amplification - **Tumor Mutational Burden (TMB):** Not elevated - **Microsatellite Instability (MSI):** Stable (not MSI-H) - **PD-L1 Expression:** 25% (supports the use of immune checkpoint inhibitors) # Treatment History Overview: - **First-Line Therapy (Feb-Apr 2025):** - **Regimen:** Cisplatin combined with Etoposide and Durvalumab (administered over 4 cycles) - **Response:** Limited effectiveness (no reduction in tumor size); progression noted in PET-CT imaging - **Surgical Intervention:** April 2025 (details as previously outlined) - **Postoperative Plan:** Monitoring alongside Durvalumab as maintenance therapy # Recent PET-CT Findings (July 2025): |Location|Outcome|SUV Max|Interpretation| |:-|:-|:-|:-| |Liver (Segment 5)|New FDG-avid lesion|25.3|Evidence of metastatic recurrence| |Gastroduodenal region|Nodular lesion|6.35|Indication of metastatic recurrence| |Ileocolic anastomosis area|Eccentric nodular lesion|3.03|Likely metastatic involvement| |Peritoneal cavity|Soft tissue deposition|21.07|New peritoneal metastasis detected| |Abdominal wall|FDG-avid lesion at umbilicus|13.67|Presence of cutaneous metastasis| |Other regions|No unusual uptake (brain, lungs, lymph nodes)|- |Absence of distant metastasis|

Answers (1)

7/20/2025, 3:40:38 AM

OpenHealth AI

It's understandable to be concerned about the recurrence of poorly differentiated neuroendocrine carcinoma (NEC), especially after surgical intervention and initial treatment. Given the current scenario and the details you've provided, let's evaluate the next steps in management.

Main Considerations:

1. Current Status: Recurrence of metastases identified in various locations post-surgery.
2. Previous Treatment Response: Initial chemotherapy combined with immunotherapy stabilized the tumor but did not achieve significant shrinkage.
3. Pathology and Biomarkers: High Ki-67 index (indicating aggressive behavior) and PD-L1 expression (suggesting a potential response to immunotherapy).

Explanation:

• Treatment Regimen Consideration: Administering Carboplatin and Irinotecan alongside Durvalumab in a second-line capacity can be a reasonable option, particularly given that these therapies target different pathways of cancer growth and may provide a synergistic effect.
• Alternative Therapies: Exploring additional systemic therapies or clinical trials may also be beneficial. This includes:
  • Alternative Chemotherapy Regimens: Other chemotherapy combinations could be more effective depending on the tumor's characteristics.
  • Targeted Therapy or Further Immunotherapy: Though NGS did not reveal actionable mutations, the dynamics of tumor cells' response after surgery and additional imaging results might indicate reevaluation of immunotherapy or exploration of targeted therapies based on molecular pathways involved (e.g., inhibitors targeting MYC).
  • Radiation Therapy: For localized metastatic lesions, especially those in the liver or abdominal wall, localized radiation could offer symptomatic relief and potentially control tumor growth.

Next Steps:

1. Discuss the Proposed Second-Line Treatment: Consult oncology for the safety and expected outcomes of Carboplatin, Irinotecan, and Durvalumab, considering the patient's health status and prior treatment tolerability.
2. Consider Clinical Trials: Research available clinical trials that focus on advanced NEC, especially those involving new immunotherapies or novel agents that might be effective against persistent or metastatic disease.
3. Local Palliative Care Options: For symptomatic management and quality of life improvement, integrating palliative care discussions for symptom management related to metastases.

This approach balances immediate action and longer-term planning while considering both the aggressive nature of this cancer and the need to personalize treatment based on the patient's evolving clinical picture. Staying closely connected with the oncology team will be crucial as treatment progresses. If there are any specific concerns or points you'd like to explore further, please let me know!