Clinical and molecular characteristics of patients with brain metastasis secondary to pancreatic ductal adenocarcinoma.

BACKGROUND: The prognosis for patients with pancreatic ductal adenocarcinoma (PDAC) is poor. Secondary brain metastasis (Br-M) occurs in less than 1% of patients. Clinical characteristics and molecular alterations have not been characterized in this rare patients' subset. MATERIALS AND METHODS: The Foundry software platform was used to retrospectively query electronic health records for patients with Br-M secondary to PDAC from 2005 to 2023; clinical, molecular, and overall survival (OS) data were analyzed. RESULTS: Br-M was diagnosed in 44 patients with PDAC. Median follow-up was 78 months; median OS from initial PDAC diagnosis was 47 months. Median duration from PDAC diagnosis to Br-M detection was 24 months; median OS from Br-M diagnosis was 3 months. At Br-M diagnosis, 82% (n = 36) of patients had elevated CA19-9. Lung was the most common preexisting metastatic location (71%) with Br-M, followed by liver (66%). Br-M were most frequently observed in the frontal lobe (34%, n = 15), cerebellar region (23%, n = 10), and leptomeninges (18%, n = 8). KRAS mutations were detected in 94.1% (n = 16) of patients who had molecular data available (n = 17) with KRASG12V being the most frequent subtype 47% (n = 8); KRASG12D in 29% (n = 5); KRASG12R in 18% (n = 3). Patients who underwent Br-M surgical resection (n = 5) had median OS of 8.6 months, while median OS following stereotactic radiosurgery only (n = 11) or whole-brain radiation only (n = 20) was 3.3 and 2.8 months, respectively. CONCLUSION: Br-M is a late PDAC complication, resulting in an extremely poor prognosis especially in leptomeningeal disease. KRAS was mutated in 94.1% of the patients and the KRASG12V subtype was prevalent.

Does a history of malignancy impact the survival of a subsequent endometrial adenocarcinoma? Should clinical trials eligibility criteria be revisited?

We aimed at finding the impact of prior malignancies on the survival of patients with endometrial adenocarcinoma using SEER database (from 1973 to 2014). We identified 127,988 patients who were diagnosed with endometrial adenocarcinoma (6485 had a prior malignancy), and we compared the overall and cancer-specific survival based on the presence or absence of a prior malignancy and the latency period between the two diagnoses using Kaplan-Meier test and Cox models. Adjusted cox models showed that a history of a prior malignancy neither affected the overall survival nor the cancer-specific survival of stage IV cases in all latency groups except the one diagnosed within 1 year of the first cancer. Therefore, there is no rational explanation for excluding stage IV endometrial adenocarcinoma patients with a prior malignancy from clinical trials except for the group that was diagnosed with endometrial adenocarcinoma within 1 year from the first cancer.Impact statementWhat is already known on this subject? Not enough evidence is found on the impact of prior malignancies on the survival of patients with subsequent endometrial adenocarcinoma.What do the results of this study add? History of a prior malignancy neither affects the overall survival of stage IV endometrial adenocarcinoma nor the cancer-specific survival. Only patients who had their second malignancy diagnosed within one year of the first malignancy should be excluded from clinical trials, while patients diagnosed within one to five years of the first cancer should be encouraged to enrol in clinical trials as they have an enhanced survival than patients without a history of malignancy.What are the implications of these findings for clinical practice and/or further research? We recommend that future researchers should consider including the aforementioned group of patients in their trials to achieve more accurate results and in order not to strip the patients of potential therapeutic benefits of enrolling in clinical trials.