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Inactivation of the cyclin-dependent kinase inhibitor 2A (CDKN2A) gene is considerably more frequent in squamous cell lung cancer (SqCLC) than in other subtypes of lung cancer and may be a promising target for this histology. Here, we present the course of diagnosis and treatment of a patient with advanced SqCLC, harboring not only CDKN2A mutation but also PIK3CA amplification, Tumor Mutational Burden-High (>10 mutations/megabase), and a Tumor Proportion Score of 80%. After disease progression on multiple lines of chemotherapy and immunotherapy, he responded favorably to treatment with the CDK4/6i Abemaciclib and later achieved a durable partial response to immunotherapy rechallenge with a combination of anti-PD-1 and anti-CTLA-4, nivolumab, and ipilimumab.

704 Background: Neoadjuvant chemotherapy improves survival in borderline resectable pancreatic cancer (RPC). Whether these results are the same in upfront RPC is unknown. Methods: To evaluate the association of neoadjuvant treatment and outcomes in RPC a systematic review was performed including randomized trials of neoadjuvant treatment versus upfront surgery. Articles indexed in PubMed, Embase and Web of Science were evaluated. Data regarding treatment regimens, R0 rates, disease free survival (DFS) and overall survival (OS) were extracted. The outcomes were compared using a random effects model. The index I2 and the graphs of funnel plot were used for the interpretation of the data. Results: Of 3,229 abstracts, 6 randomized controlled trials were considered eligible with a combined sample size of 805 patients. Among the trials, the PACT-15, JSAP-05, and updated long-term results from PREOPANC and NEONAX trials were included. In the meta-analysis, we could see that neoadjuvant treatment in RPC does not improve DFS or OS; HR 0.72 [0.46-1.09] and HR 0.76 [0.52-1.11], respectively. Interestingly, R0 rates were improved about 20% with the neoadjuvant approach (HR 1.2 [1.04-1.37]). It is important to note that most studies evaluated gemcitabine-based regimens in the neoadjuvant setting. Conclusions: This metanalysis of six randomized controlled trials suggests that neoadjuvant chemotherapy with gemcitabine-based regimens does not improve PFS or OS in RPC compared to upfront surgery followed by adjuvant treatment. Neoadjuvant treatment improves R0 rates in about 20%. Randomized ongoing trials are eagerly waited with more active combined regimens including modified FOLFIRINOX.[Table: see text]

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a public health emergency. A rare complication of this infection is spontaneous pneumomediastinum, also known as Hamman syndrome. Case report: A 58-year-old hypertensive and diabetic male presented with flu-like symptoms and respiratory failure and was subjected to orotracheal intubation and mechanical ventilation.Extensive subcutaneous emphysema and chest asymmetry were observed. Chest computed tomography also revealed a pneumomediastinum with extensive subcutaneous emphysema. The patient progressed with reduced ventilatory capacity and hemodynamic deterioration before subsequently dying. Discussion: Hamman syndrome is a marker of poor prognosis denoting worse outcomes among patients with SARS-CoV-2 infection.

Antibody-drug conjugates (ADCs) deliver effective medications to tumor cells that express specific antigens, maximizing efficacy and reducing adverse effects. Because ado-trastuzumab emtansine was approved in 2013, 5 ADCs received US Food and Drug Administration approval for solid tumor treatment. Technical advancements in the development of each component of ADCs allowed novel monoclonal antibodies, linkers, and payloads to increase drug transport to malignant cells and drug activity even in cancers with heterogeneous antigen expression. In addition, several ADCs are in development using new molecular targets expressed across a broad range of histologies to allow the use of ADC biomarker-driven therapy irrespective of the primary tumor site. This suggests that the future efficacy of ADCs in multiple histologies may be similar to other classes of drugs that are considered histology-agnostic therapies nowadays. This review focuses on novel ADCs for the treatment of solid tumors, including topics such as their structure and mechanism of action, the latest indications of already US Food and Drug Administration-approved ADCs, and the outlook for new promising ADCs under development for the treatment of tumors of various histologies.