The treatment of advanced melanoma: Current approaches and new challenges.

In recent years, advances in melanoma treatment have renewed patient hope. This comprehensive review emphasizes the evolving treatment landscape, particularly highlighting first-line strategies and the interplay between immune-checkpoint inhibitors (ICIs) and targeted therapies. Ipilimumab plus nivolumab has achieved the best median overall survival, exceeding 70 months. However, the introduction of new ICIs, like relatlimab, has added complexity to first-line therapy decisions. Our aim is to guide clinicians in making personalized treatment decisions. Various features, including brain metastases, PD-L1 expression, BRAF mutation, performance status, and prior adjuvant therapy, significantly impact the direction of advanced melanoma treatment. We also provide the latest insights into the treatment of rare melanoma subtypes, such as uveal melanoma, where tebentafusp has shown promising improvements in overall survival for metastatic uveal melanoma patients. This review provides invaluable insights for clinicians, enabling informed treatment choices and deepening our understanding of the multifaceted challenges associated with advanced melanoma management.

Can High-Frequency Intraoral Ultrasound Predict Histological Risk Factors in Oral Squamous Cell Carcinoma? A Preliminary Experience.

Despite advancements in multidisciplinary care, oncologic outcomes of oral cavity squamous cell carcinoma (OSCC) have not substantially improved: still, one-third of patients affected by stage I and II can develop locoregional recurrences. Imaging plays a pivotal role in preoperative staging of OSCC, providing depth of invasion (DOI) measurements. However, locoregional recurrences have a strong association with adverse histopathological factors not included in the staging system, and any imaging features linked to them have been lacking. In this study, the possibility to predict histological risk factors in OSCC with high-frequency intraoral ultrasonography (IOUS) was evaluated. Thirty-four patients were enrolled. The agreement between ultrasonographic and pathological DOI was evaluated, and ultrasonographic margins' appearance was compared to the Brandwein-Gensler score and the worst pattern of invasion (WPOI). Excellent agreement between ultrasonographic and pathological DOI was found (mean difference: 0.2 mm). A significant relationship was found between ultrasonographic morphology of the front of infiltration and both Brandwein-Gensler score ≥ 3 (p < 0.0001) and WPOI ≥4 (p = 0.0001). Sensitivity, specificity, positive predictive value, and negative predictive value for the IOUS to predict a Brandwein-Gensler score ≥3 were 93.33%, 89.47%, 87.50%, and 94.44%, respectively. The present study demonstrated the promising role of IOUS in aiding risk stratification for OSCC patients.

Muscle quality and not quantity as a predictor of survival in head and neck squamous cell carcinoma.

BACKGROUND: Sarcopenia is frequent in head and neck squamous cell carcinoma (HNSCC), as a consequence of malnutrition related to risk factors or tumoral mass. Treatment is associated with toxicities that lead to reduced calories intake and muscle mass wasting. Sarcopenia has been negatively associated with tumor control and survival outcomes. PURPOSE: Our aim is to evaluate the prognostic impact of sarcopenia on overall survival (OS) and progression free survival (PFS) in HNSCC patients undergoing chemoradiation therapy within a prospective clinical trial of chemoradiation vs induction chemotherapy followed by radiation and cetuximab (INTERCEPTOR). MATERIALS AND METHODS: On baseline CT or MRI, we investigated the association between OS and PFS with radiological markers of sarcopenia, measured at the third cervical vertebra level. We studied paravertebral skeletal muscles area (cm2), muscle density (HU), muscle index (cm2/m2), and intermuscular adipose tissue (IMAT) area (cm2). RESULTS: Imaging of 128 patients was evaluable. We found out that higher body mass index (BMI) was associated with better OS (p = 0.02), and PFS (p = 0.04). Skeletal muscle area (p = 0.02), and IMAT (p = 0.02) were negatively associated with PFS. IMAT was positively correlated with muscle area (Correlation coefficient 0.6, CI95% 0.47-0.7), and negatively associated with muscle density (Correlation coefficient -0.37, CI95% -0.53 - -0.18). CONCLUSIONS: IMAT can be used as predictor of PFS in HNC patients undergoing chemoradiation therapy. The amount of intermuscular fat deposits induces alterations of muscle quality, without alterations of muscle quantity, influencing patients' prognosis.

Immunotherapy for the Treatment of Cutaneous Squamous Cell Carcinoma.

Cutaneous squamous cell carcinoma (CSCC) accounts for approximately 20% of all keratinocytic tumors. In most cases, the diagnosis and treatments are made on small, low-risk lesions. However, in about 5% of cases, CSCC may present as either locally advanced or metastatic (i.e. with locoregional lymph nodes metastases or distant localizations). Prior to the introduction of immunotherapy in clinical practice, the standard treatment of advanced CSCC was not clearly defined, and up to 60% of patients received no systemic therapy. Thanks to a strong pre-clinical rationale, clinical trials led to the FDA (Food and Drug Administration) and EMA (European Medicines Agency) registration of cemiplimab, a PD-1 inhibitor that achieved encouraging results in terms of objective response, overall survival, and quality of life. Subsequently, the anti-PD-1 pembrolizumab received the approval for the treatment of advanced CSCC by the FDA only. In this review, we will focus on the definition of advanced CSCC and on the current and future therapeutic options, with a particular regard for immunotherapy.