Mucosal Melanoma: Epidemiology, Clinical Features, and Treatment.

PURPOSE OF REVIEW: Summarize the writings published in the last years on the management and novel therapies of mucosal melanoma (MM). RECENT FINDINGS: New research has demonstrated a difference between MM and cutaneous melanoma (CM) in their genomic and molecular landscapes, explaining the response's heterogeneity. Immunotherapy and targeted therapy have limited benefit, but novel therapies are rapidly expanding. MM is aggressive cancer occurring in gastrointestinal, respiratory, or urogenital mucosa; whose incidence is greater in the Asian population. The etiology and pathogenesis remain unclear since UV exposure is not a proven risk factor as in cutaneous melanoma. In contrast to CM, lesions on the mucosal surface are less likely to be recognized early; therefore, the disease is diagnosed in an advanced stage. Clinical manifestations, such as bleeding or pain, can help to detect this tumor, although the prognosis remains unfavorable with an overall 5-year survival rate of less than 20%. The mutational landscape of MM includes mutations of BRAF and NRAS, as well as mutations in the c-KIT/CD117 gene (in 50% of patients), thus limiting therapeutic interventions to immunotherapy. However, clinical studies show less responsiveness to immunotherapy compared to CM, therefore novel therapeutic strategies targeting new molecules are needed to improve the survival of patients with MM.

Checkpoint Inhibitor-Induced Colitis: An Update.

Immunotherapy with immune checkpoint inhibitors (ICIs) nowadays has indications for several solid tumors. The current targets for ICIs are CTLA-4, PD-1, and PD-L1 receptors. Despite the clinical advantages derived from ICIs, a variety of side effects are linked to overstimulation of the immune system. Among these, ICI-related colitis is one of the most common, with a disabling impact on the patient. Diarrhea, abdominal pain, abdominal distension, cramping, and hematochezia are the most common ICI enterocolitis presenting symptoms. The most frequently used grading system for assessment of the severity of ICI enterocolitis is called the Common Terminology Criteria for Adverse Events (CTCAE) grading. With regard to the histological picture, there is no specific feature; however, microscopic damage can be classified into five types: (1) acute active colitis, (2) chronic active colitis, (3) microscopic colitis-like, (4) graft-versus-host disease-like, and (5) other types. Supportive therapy (oral hydration, a bland diet without lactose or caffeine, and anti-diarrheal agents) is indicated in mild colitis. Symptomatic treatment alone or with loperamide, a low-fiber diet, and spasmolytics are recommended for low-grade diarrhea. In more severe cases, corticosteroid treatment is mandatory. In refractory cases, off-label use of biological therapies (infliximab or vedolizumab) was proposed.

Molecular Aberrations Stratify Grade 2 Astrocytomas Into Several Rare Entities: Prognostic and Therapeutic Implications.

The identification of specific molecular aberrations guides the prognostic stratification and management of grade 2 astrocytomas. Mutations in isocitrate dehydrogenase (IDH) 1 and 2, found in the majority of adult diffuse low-grade glioma (DLGG), seem to relate to a favorable prognosis compared to IDH wild-type (IDH-wt) counterparts. Moreover, the IDH-wt group can develop additional molecular alterations worsening the prognosis, such as epidermal growth factor receptor amplification (EGFR-amp) and mutation of the promoter of telomerase reverse transcriptase (pTERT-mut). This review analyzes the prognostic impact and therapeutic implications of genetic alterations in adult LGG.

Biliary tract cancers: moving from the present standards of care towards the use of immune checkpoint inhibitors.

Biliary tract cancers (BTCs) are aggressive and chemoresistant tumors associated with poor prognosis. Thus, more active and effective treatments are urgently needed, among which immunotherapy holds promise for the near future. Preclinical data show that BTCs are mainly immunosuppressed cancers, thus suggesting that their immunogenic potential may be unleashed with the appropriate strategy. Immune checkpoint inhibitors (ICIs) could theoretically be effective in BTCs by blocking those inhibitory checkpoints that limit the activation and the expansion of the effector cells of the immune response. Many currently ongoing trials aim to demonstrate the efficacy of ICIs and to incorporate immunotherapy into the routine management of BTCs. Presently available results are controversial and there is no consensus on the role of ICIs in monotherapy, while combinations of immunotherapy with chemotherapy look more promising. Nevertheless, despite the many proposed over time, there are no predictive biomarkers presently available, thus, the early identification of those patients showing a good response is of great significance.