Peptide receptor radionuclide therapy (PRRT) in metastatic neuroendocrine tumors of unknown primary (CUP-NETs).

Rationale: Peptide receptor radionuclide therapy (PRRT) for the treatment of neuroendocrine tumors (NETs) has been explored for more than two decades, but there are only limited data on the treatment of NETs of unknown primary site (CUP-NETs). This study aimed to analyze the long-term outcome, efficacy, and safety of PRRT in patients with CUP-NETs. Methods: Patients with pathologically confirmed metastatic CUP-NET who received lutetium-177 (177Lu) and/or yttrium-90 (90Y) labeled somatostatin analogs between March 2001 and March 2019 were retrospectively reviewed; those patients were referred as cCUP-NETs (clinical CUP-NETs). Eighty-one patients had unknown primary tumors even after [68Ga]Ga-SSTR and [18F]FDG PET/CT and were classified as pCUP-NETs (PET CUP-NETs). Treatment response was assessed according to RECIST 1.1 and PERCIST. Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier analysis, and adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. Results: A total of 575 PRRT cycles were administered to 156 patients (76 men and 80 women) evaluable for analysis: these patients were monitored for a median period of 92.3 mo (range, 4.0-169.1 mo). The disease control rate was 41.4% (43.4%) by RECIST and 40.2% (40.8%) by PERCIST in cCUP-NENs (pCUP-NETs). The objective response rate (ORR) with PRRT was 29.4% and 32.2% in cCUP-NENs and pCUP-NETs, respectively. The median PFS and OS for the entire cohort were 17.4 mo (95% confidence interval [95% CI], 11.4-23.4) and 67.4 mo (95% CI, 47.2-87.2) for all patients, respectively. The median OS for G3 tumors was significantly lower (15 mo) than for patients with G1 NET (85.5 mo), G2 (71.7 mo), and for patients with unknown grade (63.3 mo) NETs (P = 0.186, HR: 10.6, 95% CI: 3.87, 28.97, P = 0.09). PRRT was well tolerated by all patients. During treatment and long-term follow-up, CTCAE grade 3 and grade 4 thrombocytopenia and leukocytopenia were observed in only 3 patients (1.9%); there was no evidence of renal or hepatic toxicity. Conclusion: In a large cohort of patients with advanced CUP-NETs treated with PRRT in a real-world scenario and followed up to 14 years after the commencement, PRRT has demonstrated favorable and clinically significant efficacy and survival with minimal and acceptable side effects. Our results indicate that PRRT is a well-tolerated and effective treatment option for patients with metastatic CUP-NETs expressing somatostatin receptors.

Triple-negative breast cancer possibly transforming into malignant melanoma due to targeted therapy? A case report and review of literature.

BACKGROUND: Triple-negative breast cancer (TNBC) is characterized by lacking expression of estrogen receptor and progesterone receptor as well as absence of human epidermal growth factor receptor 2 overexpression and is an aggressive clinical phenotype. PATIENTS AND METHODS: We report the case of a 33-year-old woman who has been treated using a targeted approach for TNBC and developed a malignant melanoma metastasis without any primary. RESULTS AND CONCLUSION: Using targeted therapies, tumors can be treated much more effectively, but up to now, we do not know much about potential adverse reactions. Due to the targeted therapy, tumors may be pressurized for transformation. We call for further investigations to rule out the potential risks of targeted therapy in TNBC. This is the first report of a potential transforming of one tumor entity to another by a targeted therapy.

Assessing risk and mortality of venous thromboembolism in pancreatic cancer patients.

BACKGROUND: Venous thromboembolism (VTE) is associated with cancer. Cancer patient with thromboembolism have poorer prognosis. This study assessed the risk and mortality in pancreatic cancer patients who develop VTE. PATIENTS AND METHODS: A retrospective chart review was performed of 201 patients with pancreatic cancer. RESULTS: VTE was observed in 58 (28.9%) patients, 37/58 had deep vein thrombosis (DVT), 11/58 pulmonary embolism (PE) and 10/58 had both. Twenty-six out of 107 patients with tumor of head of the pancreas developed VTE (24%), compared to half of the patients with body of the pancreas involvement (11-22). Stage IV was defined in 99 patients, 39/99 had VTE (39%). Median survival time was 14.95 months for patients without VTE compared to 13.04 months with VTE. CONCLUSION: Patients with body of the pancreas and stage IV tumors had increased risk of developing VTE. There was no survival difference between patients with VTE compared to those without.

Absence of carcinogenic activity in Fischer rats and B6C3F1 mice following 103-week inhalation exposures to toluene.

Toluene, methylbenzene, is used to back-blend gasoline, as a chemical intermediate, and as a solvent; more than 7 million tonnes are produced each year in the United States. Following 14-15-week toxicity studies to estimate appropriate exposure concentrations for the carcinogenesis bioassays, toxicology and carcinogenesis studies of toluene (>99% pure) were conducted by whole-body inhalation exposures of F344/N rats and B6C3F1 mice of each sex for 15 months or two years. Toluene levels were 0 (chamber controls), 600, and 1,200 ppm for rats and 0, 120, 600, and 1200 ppm for mice. Exposures were 6.5 hr/day 5 days/wk. Genetic toxicology studies using Salmonella typhimurium, mouse L5178Y lymphoma cells, and Chinese hamster ovary cells were negative. No chemically related neoplasm was found in male rats, and one nasal, two kidney, and two forestomach neoplasms observed in female rats were considered not to be associated with the toluene exposure. For mice, no biologically important increase was observed for any nonneoplastic or neoplastic lesion. Studies by others had reported carcinogenicity of toluene, especially for total malignant tumors.