SDHx mutations and temozolomide in malignant pheochromocytoma and paraganglioma.

Malignant pheochromocytomas (PHEOs)/paragangliomas (PGLs) are rare tumors for which clinical outcomes remain poorly defined and therapeutic options are limited. Approximately 27% carry pathogenic germline succinate dehydrogenase (SDHx) mutations; the presence of such mutations has been correlated with response to temozolomide (TMZ). We aimed to investigate the association between germline mutations in SDHx and response to TMZ. We retrospectively identified patients with metastatic malignant PHEO/PGLs treated with TMZ- based chemotherapy at Dana-Farber Cancer Institute between 2003 and 2020. The correlation between response by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and PET Response Criteria in Solid Tumors (PERCIST) and the presence of SDHx mutations in the germline and tumor was evaluated. Nineteen patients received TMZ. Seventeen underwent germline assessment: 9 (53%) carried a pathogenic SDHx germline mutation. Fifteen patients were evaluable for response by RECIST 1.1: 6 (40%) partial response, 4 (27%) stable disease, and 5 (33%) progressive disease. Overall median progression-free survival was 2.2 years. Three-year overall survival (OS) was 58%. Median PFS was 1.3 years and 5.5 years for carriers and non-carriers, respectively and OS was 1.5 years and not estimable for carriers and non-carriers, respectively. The response by PERCIST criteria in nine patients correlated with the RECIST 1.1 assessment. Our series represents one of the largest analyses of patients with malignant PHEOs/PGLs treated with TMZ who have available germline data. The incidence of pathogenic germline SDHx mutations was similar to what has been previously published, though our analysis suggests that there may be a limited association between response to TMZ and pathogenic germline SDHx mutations.

Benefit of Primary Tumor Resection in Stage IV, Grade 1 and 2, Pancreatic Neuroendocrine Tumors: A Propensity-Score Matched Cohort Study.

Objective: To determine the association of primary tumor resection in stage IV pancreatic neuroendocrine tumors (Pan-NET) and survival in a propensity-score matched study. Background: Pan-NET are often diagnosed with stage IV disease. The oncologic benefit from primary tumor resection in this scenario is debated and previous studies show contradictory results. Methods: Patients from 3 tertiary referral centers from January 1, 1985, through December 31, 2019: Uppsala University Hospital (Uppsala, Sweden), Sahlgrenska University Hospital (Gothenburg, Sweden), and Brigham and Women's Hospital/Dana-Farber Cancer Institute (Boston, USA) were assessed for eligibility. Patients with sporadic, grade 1 and 2, stage IV pan-NET, with baseline 2000-2019 were divided between those undergoing primary tumor resection combined with oncologic treatment (surgery group [SG]), and those who received oncologic treatment without primary tumor resection (non-SG). A propensity-score matching was performed to account for the variability in the extent of metastatic disease and comorbidity. Primary outcome was overall survival. Results: Patients with stage IV Pan-NET (n = 733) were assessed for eligibility, 194 were included. Patients were divided into a SG (n = 65) and a non-SG (n = 129). Two isonumerical groups with 50 patients in each group remained after propensity-score matching. The 5-year survival was 65.4% (95% CI, 51.5-79.3) in the matched SG and 47.8% (95% CI, 30.6-65.0) in the matched non-SG (log-rank, P = 0.043). Conclusions: Resection of the primary tumor in patients with stage IV Pan-NET and G1/G2 grade was associated with prolonged overall survival compared to nonoperative management. A surgically aggressive regime should be considered where resection is not contraindicated.