# Primary Tumor Size and Tumor–Vessel Interface Following Capecitabine and Temozolomide for Pancreatic Neuroendocrine Tumor

## TL;DR

This study examines how the chemotherapy combination CAPTEM affects tumor size and its relationship with blood vessels in pancreatic neuroendocrine tumors.

## Contribution

The study provides new insights into the limited impact of CAPTEM on tumor-vascular interface changes and resectability in pancreatic neuroendocrine tumors.

## Key findings

- Only 16.2% of patients showed changes in the tumor–vascular interface after CAPTEM treatment.
- Objective radiographic response in the primary tumor was observed in 6.4% of patients.
- Four patients transitioned from unresectable to anatomically resectable tumors following CAPTEM.

## Abstract

Pancreas neuroendocrine tumors can be treated with a combination of chemotherapy agents called capecitabine and temozolomide. While this treatment can be associated with tumor shrinkage, we were interested to know if treatment could also be associated with a response around nearby blood vessels, often a limiting factor in primary tumor resection. Of patients treated with this drug combination, only 16.2% had changes in the vascular relationship of the tumor to the blood vessels. The utility of radiographic response or primary tumor association with the mesenteric blood vessels as a marker of potential resectability is thus not known.

Capecitabine/temozolomide (CAPTEM) is an established regimen for patients with metastatic pancreatic neuroendocrine tumors (PanNET) that is being increasingly used for tumor volume reduction in patients with borderline anatomically resectable disease. We sought to understand the response of the primary tumor, defined as changes in the tumor–vascular interface (TVI). This is a retrospective, single-institution study of patients with locally advanced or metastatic PanNET treated with CAPTEM between 2010 and 2020. RECISTv1.1 measurements and TVI assessments of the primary tumor were performed on pre- and post-therapy images. Patients with locally advanced or metastatic PanNET at presentation (n = 47) were included. CAPTEM was given for a median of 11 cycles. The most common site of metastatic disease was the liver (n = 38). An objective radiographic response in the primary tumor was observed in 6.4% (95% CI 1.7–18.6%) with clinical benefit in 70.2% (95% CI 54.9–82.2%). TVI was modified from >180° to ≤180° in 16.2% (95% CI 6.0–45.5%). Paired analysis of patients pre- and post-CAPTEM did not demonstrate a statistically significant shift in TVI with treatment (p = 0.134). A total of four patients had a change from an unresectable primary tumor to an anatomically resectable tumor following CAPTEM. In patients with locally advanced or metastatic PanNET, treatment with CAPTEM is associated with low radiographic response rates and changes in TVI. The degree to which these changes may correlate with surgical resection rates or R0 resections is not known. Extending these investigations in a cohort of PanNET patients offered CAPTEM for neoadjuvant intent could be helpful to understand whether these phenomena persist in that context.