A Case of Metastatic Pancreatic Adenocarcinoma in Complete Remission Using Chemotherapy and Immunotherapy.

Among the various types of cancer, pancreatic cancer is considered to have a particularly grim prognosis. Treatment includes surgery, chemotherapy, or both. While the role of immunotherapy is well-studied in many types of cancer, such is not the case with pancreatic cancer. A 49-year-old female presented to the oncology clinic following a biopsy of a pancreatic mass. CT-guided needle biopsy of the mass demonstrated moderately differentiated pancreatic adenocarcinoma. Positive emission tomography-computed tomography (PET-CT) revealed metastases to the liver. She was started on chemotherapy with FOLFIRINOX (leucovorin calcium, 5-fluorouracil, irinotecan hydrochloride, oxaliplatin) and demonstrated over 60% reduction in the size of liver metastases within three months. PET-CT four months after initiation of chemotherapy revealed no focal avid fluorodeoxyglucose (FDG) uptake in the liver, and the pancreatic body mass was stable in size at 3.0 cm with stable standardized uptake value (SUV) max at 2.4, only slightly elevated from 1.9 on the previous scan. Further treatment with chemotherapy was halted after 18 cycles due to side effects. With the patient's tumor being epidermal growth factor receptor (EGFR) negative, mismatch repair (MMR) negative, 3% tumor cells PD-L1 positive with 10% tumor-associated immune cells positive, treatment with pembrolizumab was started. Follow-up PET-CTs over the next several months confirmed the patient was in complete remission from metastatic pancreatic cancer. At the time of the report, the patient had a durable response of three years. We report a rare case of complete remission of metastatic pancreatic adenocarcinoma treated with chemotherapy, followed by immunotherapy. With emerging targets for modification of tumor microenvironment, immunotherapy must be further explored in the treatment of pancreatic cancer.

Pembrolizumab-Induced Cold Agglutinin Disease.

BACKGROUND The introduction of immunotherapy in the management of metastatic lung cancer appears to be changing their natural history. Most patients tolerate immunotherapy without any significant adverse events. Nevertheless, a significant number of patients still experience adverse effects. Autoimmune hemolytic anemia has been described as mostly related to warm autoantibodies. The following case report describes cold agglutinin disease with hemolysis secondary to Pembrolizumab therapy for the treatment of metastatic lung cancer. CASE REPORT A 58-year-old woman noted a left neck mass 4 months prior to her presentation. A biopsy confirmed the presence of metastatic adenocarcinoma, consistent with primary lung cancer. Further evaluation revealed the tumor to be PDL-1-positive. She was started on Pembrolizumab, Pemetrexed, and carboplatin chemotherapy regimen. Her CBC was within normal limits when she started therapy, but within 4 weeks hemoglobin dropped to 4.3 g/dL. Further evaluation showed high cryoglobulin levels and a high cold agglutinin titer. Complement C3 DAT was positive. A peripheral smear showed clumps of red cells and the serum IgM was elevated. The diagnosis of CAD was made. She was then started on Rituximab. Imaging showed a significant response, with decreased disease burden. CONCLUSIONS Our case shows a unique presentation of CAD, initially presumed to be myelosuppression secondary to chemotherapy. Instead, a peripheral smear revealed Pembrolizumab to be the cause of cold agglutinin disease. Due to the relatively unknown association between these 2 entities, patient care was delayed. Finally, after initiation of Rituximab therapy, the patient's CBC began to recover.

Sirt2-associated transcriptome modifications in cisplatin-induced neuronal injury.

BACKGROUND: Chemotherapy-induced peripheral neuropathy is not only one of the most common causes of dose reduction or discontinuation of cancer treatment, but it can also permanently decrease the quality of life of cancer patients and survivors. Notably, Sirt2 protects many organs from various injuries, including diabetic peripheral neuropathy. As demonstrated previously by our laboratory and others, the overexpression of Sirt2 can improve cisplatin-induced neuropathy, although the mechanism is still unclear. RESULTS: In this study, the underlying mechanism by which Sirt2 protects neurons from cisplatin-induced injury was explored using the RNAseq technique in cultured rodent neurons. Sirt2 status was modified by genetic knockout (Sirt2/KO) and was then reconstituted in Sirt2/KO cells (Sirt2/Res). We observed 323 upregulated genes and 277 downregulated genes in Sirt2-expressing cells (Sirt2/Res) compared to Sirt2-deficient cells (Sirt2/KO). Pathway analysis suggested that Sirt2 may affect several pathways, such as MAPK, TNF, and cytokine-cytokine interaction. Furthermore, cisplatin-induced changes to the transcriptome are strongly associated with Sirt2 status. Cisplatin induced distinctive transcriptome changes for 227 genes in Sirt2-expressing cells and for 783 genes in Sirt2-deficient cells, while changes in only 138 of these genes were independent of Sirt2 status. Interestingly, changes in the p53 pathway, ECM-receptor interactions, and cytokine-cytokine receptor interactions were induced by cisplatin only in Sirt2-deficient cells. CONCLUSIONS: This study demonstrated that Sirt2 regulates the transcriptome in cultured rodent neuronal cells. Furthermore, Sirt2-associated transcriptome regulation may be an important mechanism underlying the role of Sirt2 in organ protection, such as in cisplatin-induced neuronal injury. Sirt2 may be a potential target for the prevention and treatment of chemotherapy-induced neuropathy.