Abstract 599: Secondary malignancies in temozolomide-treated metastatic pancreatic neuroendocrine tumors
Authors: Balmaceda Nicole , Abhyankar Sunil , Mouw Tyler , Baranda Joaquina 
Published: August 2018

Abstract
Purpose: To determine the incidence of secondary malignancies in patients treated with temozolomide (TMZ) for metastatic pancreatic neuroendocrine tumors (PNET).
Background: TMZ is an oral alkylating agent used to treat glioblastoma multiforme (GBM), refractory anaplastic astrocytoma (AA), and metastatic PNET. This imidazotetrazine analog of dacarbazine lacks the ability to directly crosslink DNA and is thought to be less leukemogenic than other alkylators. Given either alone, or in combination with other therapies, TMZ is associated with improved clinical outcomes. However, serious hematologic adverse events (HAEs) like agranulocytosis, lymphopenia and aplastic anemia are not uncommon. Until recently, metastatic PNET was primarily managed with somatostatin-analogs, but with more reports demonstrating therapeutic activity of TMZ-based regimens, it is anticipated that more patients with metastatic PNET will be exposed to TMZ.
Methods: To determine the incidence of secondary malignancy in TMZ-treated PNET, a systematic review of all known clinical trials, case reports, and other relevant literature regarding PNET and TMZ published before September 2017 was conducted using PubMed, Embase, Cochrane Library, and the FDA database.
Results: Twenty-one publications, including clinical trials, meta-analyses, case reports, and cohort studies were analyzed. HAEs ranged from agranulocytosis to myelodysplastic syndrome. No publications reported any secondary malignancies. Incidentally, at the University of Kansas Medical Center, 3 patients with TMZ-treated PNET developed hematologic malignancies. A 29-year-old female with metastatic PNET was treated with TMZ and subsequently developed acute myeloid leukemia (AML) with cytogenetics consistent with therapy-related leukemia. The second patient with TMZ-treated metastatic PNET developed diffuse large B-cell lymphoma. These two patients both had aggressive disease that was not responsive to multiple rounds of treatment. They succumbed to their hematologic malignancy, and not from metastatic PNET. The third patient is a 29-year-old who was recently diagnosed with high-grade T-cell lymphoblastic lymphoma and is currently undergoing treatment for his lymphoma.
Conclusion: This review did not find any cases of secondary malignancy in TMZ-treated metastatic PNET. Yet, at our own institution we have identified 3 cases of secondary hematologic malignancies in patients treated with TMZ for PNET. We believe that the leukemogenic potential of TMZ is underreported and anticipate increased reports of secondary malignancy as the use of TMZ increases. It is important for treatment guidelines to address this risk in the decision to pursue TMZ treatment. Appropriate dosing, proper follow-up and surveillance, especially in patients who are able to live long enough to develop these hematologic cancers, is crucial.
Citation Format: Nicole Balmaceda, Sunil Abhyankar, Tyler Mouw, Joaquina Baranda. Secondary malignancies in temozolomide-treated metastatic pancreatic neuroendocrine tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 599.