Real-world evidence regarding molecular epidemiology and management patterns of patients with EGFR exon-20 mutated, advanced NSCLC outside the context of clinical trials is lacking. We created a European registry for patients with advanced EGFR exon 20-mutant NSCLC diagnosed from January 2019 to December 2021. Patients enrolled in clinical trials were excluded. Clinicopathologic and molecular epidemiology data were collected, and treatment patterns were recorded. Clinical end points according to treatment assignment were assessed using Kaplan-Meier curves and Cox regression models. Data on 175 patients from 33 centers across nine countries were included in the final analysis. Median age was 64.0 (range: 29.7-87.8) years. Main features included female sex (56.3%), never or past smokers (76.0%), adenocarcinoma (95.4%), and tropism for bone (47.4%) and brain (32.0%) metastases. Mean programmed death-ligand 1 tumor proportional score was 15.8% (range: 0%-95%) and mean tumor mutational burden was 7.06 (range: 0-18.8) mutations per megabase. Exon 20 was detected in the tissue (90.7%), plasma (8.7%), or both (0.6%), using mostly targeted next-generation sequencing (64.0%) or polymerase chain reaction (26.0%). Mutations were mainly insertions (59.3%), followed by duplications (28.1%), deletions-insertions (7.7%), and the T790M (4.5%). Insertions and duplications were located mainly in the near loop (codons 767-771, 83.1%) and the far loop (codons 771-775, 13%) and only in 3.9% within the C helix (codons 761-766). Main co-alterations included mutations in TP53 (61.8%) and MET amplifications (9.4%). Treatment on mutation identification included chemotherapy (CT) (33.8%), CT-immunotherapy (IO) (18.2%), osimertinib (22.1%), poziotinib (9.1%), mobocertinib (6.5%), mono-IO (3.9%), and amivantamab (1.3%). Disease control rates were 66.2% with CT plus or minus IO, 55.8% with osimertinib, 64.8% with poziotinib, and 76.9% with mobocertinib. Corresponding median overall survival was 19.7, 15.9, 9.2, and 22.4 months, respectively. In multivariate analysis, type of treatment (new targeted agents versus CT ± IO) affected progression-free survival (p = 0.051) and overall survival (p = 0.03). EXOTIC represents the largest academic real-world evidence data set on EGFR exon 20-mutant NSCLC in Europe. Indirectly compared, treatment with new exon 20-targeting agents is likely to confer survival benefit than CT plus or minus IO.

Introduction Nail toxicity represents one of the most common cutaneous adverse effects of both classic chemotherapeutic agents and new oncologic drugs, including targeted treatments and immunotherapy. Objectives We aimed to provide a comprehensive literature review of nail toxicities derived from conventional chemotherapeutic agents, targeted therapies (EGFR inhibitors, multikinase inhibitors, BRAF and MEK inhibitors) and immune checkpoint inhibitors (ICIs), including clinical presentation, implicated drugs and approaches for prevention and management. Methods Retrieved literature from PubMed registry database was reviewed to include all articles published up to May 2021 relevant to the clinical presentation, diagnosis, incidence, prevention, and treatment of oncologic treatment-induced nail toxicity. The was searched for relevant studies. Results A wide spectrum of nail toxicities is associated with both, conventional and newer anticancer agents. The frequency of nail involvement, especially with immunotherapy and new targeted agents remains unknown and patients with different cancer types receiving different regimens may develop the same nail disorder, whereas patients with the same type of cancer under the same chemotherapeutic treatment may develop different types of nail alterations. The underlying mechanisms of the varying individual susceptibility and the diverse nail responses to various anticancer treatments need further investigation. Conclusion Early recognition and treatment of nail toxicities can minimize their impact, allowing better adherence to conventional and newer oncologic treatments. Dermatologists, oncologists and other implicated physicians should be aware of these burdensome adverse effects in order to guide management and prevent impairment of patients’ quality of life.

Radiation therapy (RT) treatment for head and neck cancer has been associated with dysphagia manifestation leading to worse outcomes and decrease in life quality. In this study, we investigated factors leading to dysphagia and treatment prolongation in patients with primaries arising from oral cavity or oropharynx that were submitted to radiation therapy concurrently with chemotherapy. The records of patients with oral cavity or oropharyngeal cancer that received RT treatment to the primary and bilateral neck lymph nodes concurrently with chemotherapy were retrospectively reviewed. Logistic regression models were used to analyze the potential correlation between explanatory variables and the primary (dysphagia ≥ 2) and secondary (prolongation of total treatment duration ≥ 7 days) outcomes of interest. The Toxicity Criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC) were used to evaluate dysphagia. A total of 160 patients were included in the study. Age mean was 63.31 (SD = 8.24). Dysphagia grade ≥ 2 was observed in 76 (47.5%) patients, while 32 (20%) experienced treatment prolongation ≥ 7 days. The logistic regression analysis showed that the volume in the primary site of disease that received dose ≥ 60 Gy (≥118.75 cc, p < 0.001, (OR = 8.43, 95% CI [3.51–20.26]) and mean dose to the pharyngeal constrictor muscles > 40.6 Gy (p < 0.001, OR = 11.58, 95% CI [4.84–27.71]) were significantly associated with dysphagia grade ≥ 2. Treatment prolongation ≥ 7 days was predicted by higher age (p = 0.007, OR = 1.079, 95% CI [1.021–1.140]) and development of grade ≥ 2 dysphagia (p = 0.005, OR = 4.02, 95% CI [1.53–10.53]). In patients with oral cavity or oropharyngeal cancer that receive bilateral neck irradiation concurrently with chemotherapy, constrictors mean dose and the volume in the primary site receiving ≥ 60 Gy should be kept below 40.6 Gy and 118.75 cc, respectively, whenever possible. Elderly patients or those that are considered at high risk for dysphagia manifestation are more likely to experience treatment prolongation ≥ 7 days and they should be closely monitored during treatment course for nutritional support and pain management.

Purpose: In this study we sought to investigate factors associated to dysphagia and subsequent need for percutaneous gastrostomy (PEG) usage, in patients with head and neck cancer receiving radiation therapy.

Background/Objectives: Gastric cancer (GC) is the fifth leading cause of cancer-related mortality. CLDN18.2 is a tight junction protein, expressed in gastric mucosa and is considered as a novel therapeutic target. Even though CLDN18.2 is associated with various components of the tumor microenvironment and the relation with clinical histopathological parameters has been widely studied, there is no sufficient data on the associations of CLDN18.2 expression and the components of the tumor microenvironment. This systematic review aims to gather and present all available data about the correlation of CLDN 18.2 expression and the tumor microenvironment. Methods: The research questions were systematically formulated using the PICO model to ensure clarity and precision, and the PRISMA flow diagram was constructed to detail the study selection process. Results: Sixteen original articles were retrieved. The major finding of this study was the positive correlation between CLDN18.2 expression and CD8+ T cells, neutrophils and cancer-associated fibroblasts. No correlation was found between CLDN18.2 expression and Tregs and B cells. For the remaining components of the microenvironment, there are contradictory data about their correlation with the expression of CLDN18.2. Conclusions: The tumor microenvironment plays a critical role in cancer progression and needs to be studied more thoroughly.

Background: Primary and secondary gallbladder melanomas are rare, and only 58 cases have been reported in scientific literature to date. This paper aimed to explore the role of minimally invasive surgery in the management of gallbladder metastatic melanomas.Case: Herein, we present the case of a 68‐year‐old man with metastatic gallbladder melanoma who was treated with laparoscopic cholecystectomy. Our case management was then compared with that of other cases reported in the literature.Conclusion: Currently, metastatic melanomas can be considered as a potentially curable disease. Palliation of symptoms and fast recovery following minimally invasive procedures could be beneficial for these patients. Particularly, laparoscopic procedures appear to prolong the survival of gallbladder melanoma patients.