Vitamin D in melanoma: Controversies and potential role in combination with immune check-point inhibitors

The role of vitamin D in melanoma is still controversial. Although several Authors described a correlation between vitamin D deficiency and poor survival in metastatic melanoma patients, clinical trials exploring the effects of vitamin D supplementation in this clinical setting were mostly inconclusive. However, recent evidence suggests that vitamin D exerts both anti-proliferative effects on tumor cells and immune-modulating activities, that have been widely explored in auto-immune disorders. On the one hand, vitamin D has been shown to inhibit T-helper17 lymphocytes, notoriously involved in the pathogenesis of immune-related adverse events (iAEs) which complicate immune-checkpoint inhibitor (ICI) treatment. On the other hand, vitamin D up-regulates PDL-1 expression on both epithelial and immune cells, suggesting a synergic effect in combination with ICIs, for which further investigation is needed

The role of “closed abdomen” hyperthermic intraperitoneal chemotherapy (HIPEC) in the palliative treatment of neoplastic ascites from peritoneal carcinomatosis: report of a single-center experience

Purpose: The purpose of this study was to review the results of a single-center experience in the management of “closed abdomen” hyperthermic intraperitoneal chemotherapy (HIPEC) using a sophisticated technical device (EXIPER®) in the palliative setting of neoplastic ascites from peritoneal carcinomatosis in patients with advanced cancer of different primary sites. Patients and methods: The study was an open, prospective, single-center, non-randomized study conducted at the Department of Medical Oncology 1, University of Cagliari, Italy, from May 2006 to October 2012. Fifteen patients with peritoneal carcinomatosis were treated with HIPEC: 5 males and 10 females (age range 51–82, median 62 years), for a total of 30 procedures (5 patients were treated more than once). Malignant ascites were from ovarian, uterine cervical, colorectal, gastric, malignant pleural mesothelioma, and unknown primary cancer. Main endpoints were increase of free interval between two consecutive procedures, progressive reduction of ascites volumes and improvement of quality of life assessed with ECOG performance status and EORTC QLQ-C30 questionnaire, and improvement of immunologic function. Results: Twelve patients were completely evaluable while three patients were “lost” to follow-up. The treatment was well tolerated. The mean free interval between two consecutive drainages increased from 11.2 to 39.5 days. The mean ascites volume drained decreased from 7.8 to 1.8 l. ECOG PS improved in the majority of patients and EORTC QLQ-C30 scores in all patients as well as immunologic function. In September 2015, only one patient was still alive. Conclusions: Our study shows that good results may be achieved in terms of symptom palliation and improvement of quality of life in very advanced cancer patients with MA from PC. The treatment was generally well tolerated considering the limited treatment options available for these patients

Thyroid dysfunction and ultrasonography features in patients with metastatic colorectal cancer treated with Regorafenib. Results from a single centre prospective cohort study.

INTRODUCTION: Regorafenib (Reg) a Tyrosine kinase inhibitor (TKI) recently approved for the treatment of metastatic colorectal cancer patients could be responsible, like others TKIs of potential endocrine side effects, but scanty data are presently available on this specific drug. METHODS: Prospective evaluation of thyroid function, autoimmunity and morphology during treatment with Regorafenib. From November 2015, 17 consecutive patients (7 males and 10 females; mean age 64.2 ± 7.8) with metastatic colorectal cancer with comparable tumor staging, normal thyroid function and no evidence of associated thyroid autoimmunity, were studied before and at monthly intervals after beginning Regorafenib at scheduled dose of 160 mg oral daily according to standard protocols. In all cases FT3, FT4, TSH and thyroid antibodies (TgAb and TPOAb) were measured together with clinical assessment and thyroid ultrasonography up to five months. RESULTS: 8/17 patients (66%) became hypothyroid (TSH 7.9 ± 4.9 mIU/l, range 7.0–18.5) within 30 days of therapy. Interestingly, in 4 of those who developed higher degree of hypothyroidism, we observed highest score of fatigue (G3), the most common general serious adverse event during Reg administration. TPOAb became detectable in 2 (12%) patients 1 month after therapy. Thyroid volume significantly decreased in 9 (52%) patients (from 8.6 ± 2.2 ml before to 4.8 ± 1.6 ml 5 months after Reg, p < 0.01 by paired Student t test), together with the appearance of mild hypoechogenicity and a significant reduction of parenchymal thyroid vascularity (p < 0.05). RESULTS: These data indicate that Reg, similarly to other TKIs inhibitors, may rapidly cause hypothyroidism in about one half of patients, and probably trigger thyroid autoimmunity. An early diagnosis and management of hypothyroidism is therefore mandatory for an effective clinical control of fatigue in most of the cases, in order to prevent unnecessary Reg dose reductions and modifications. Further studies are needed to characterize longer-term effects on thyroid function/autoimmunity and to assess whether hypothyroidism may have a prognostic value as a potential biomarker of clinical response

Current status and perspectives in immunotherapy for metastatic melanoma

Metastatic melanoma was the first malignancy in which immune checkpoint inhibitors demonstrated their successful efficacy. Currently, the knowledge on the interaction between the immune system and malignant disease is steadily increasing and new drugs and therapeutic strategies are overlooking in the clinical scenario. To provide a comprehensive overview of immune modulating drugs currently available in the treatment of melanoma as well as to discuss of possible future strategies in the metastatic melanoma setting, the present review aims at analyzing controversial aspects about the optimal immunomodulating treatment sequences, the search for biomarkers of efficacy of immunocheckpoint inhibitors, and innovative combinations of drugs currently under investigation