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Growing research has focused on obesity as a prognostic factor during therapy with immune-checkpoint inhibitors (ICIs). The role of body-mass index (BMI) in predicting response and toxicity to ICIs is not clear, as studies have shown inconsistent results and significant interpretation biases. We performed a systematic review to evaluate the relationship between BMI and survival outcomes during ICIs, with a side focus on the incidence of immune-related adverse events (irAEs). A total of 17 studies were included in this systematic review. Altogether, the current evidence does not support a clearly positive association of BMI with survival outcomes. Regarding toxicities, available studies confirm a superimposable rate of irAEs among obese and normal weight patients. Intrinsic limitations of the analyzed studies include the retrospective nature, the heterogeneity of patients’ cohorts, and differences in BMI categorization for obese patients across different studies. These factors might explain the heterogeneity of available results, and the subsequent absence of a well-established role of baseline BMI on the efficacy of ICIs among cancer patients. Further prospective studies are needed, in order to clarify the role of obesity in cancer patients treated with immunotherapy.
Among angiosarcomas, radiation-induced breast sarcomas (RIBS) represent a well-known entity generally characterized by a poor outcome, especially in patients with advanced disease. Despite the unfavorable prognosis, some chemotherapeutic agents have been used to treat these malignancies, occasionally with success. Treatments with demonstrated activity against sarcomas include ifosfamide-based regimens and, more recently, taxane derivatives. We report a case of a patient having a secondary breast angiosarcoma recurring early after surgery, who achieved complete remission following treatment with weekly paclitaxel. After 4 years of maintenance therapy, with an interval between consecutive administrations of no longer than 3 weeks, the patient is still in complete remission. A locoregional recurrence was documented twice during this period, the first as a consequence of a brief treatment interruption and the second because of a treatment delay. Nonetheless, in both instances a new complete remission was rapidly achieved with the resumption of the same treatment, without evidence of any significant adverse effects. We discuss the highly unusual behavior of this malignancy and the possible role of the two different mechanisms of action of paclitaxel-antiangiogenic versus cytotoxic-depending on the schedule of administration, with evidence of "false" drug-resistance.
Biliary tract cancers are anatomically distinct and genetically diverse tumors, evenly characterized by poor response to standard treatments and a bleak outlook. The advent of comprehensive genomic profiling using next-generation sequencing has unveiled a plethora of potentially actionable aberrations, changing the view of biliary tract cancers from an “orphan” to a “target-rich” disease. Recently, mutations in isocitrate dehydrogenase genes (IDH1/2) and fusions of the fibroblast growth factor receptor have emerged as the most amenable to molecularly targeted inhibition, with several compounds actively investigated in advanced-phase clinical trials. Specifically, the IDH1 inhibitor ivosidenib has been the first targeted agent to show a survival benefit in a randomized phase III trial of cholangiocarcinoma patients harboring IDH1 mutations. In this review article, we will focus on the IDH1/IDH2 pathway, discussing the preclinical rationale of its targeting as well as the promises and challenges of the clinical development of IDH inhibitors in biliary tract cancers.
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