Search

Aims To study programmed death ligand 1 ( PD-L1) expression, tumour-infiltrating T lymphocytes ( TILs) and the molecular context in patients with early-stage squamous cell lung carcinomas ( SCCs). Methods and results The study included samples from 40 patients (discovery cohort) and 29 patients (validation cohort) diagnosed with early-stage SCC. PD-L1 immunohistochemistry ( IHC) was performed with three commercially available clones (E1L3N, SP263 and SP142). CD8+ TILs were scored with a digital algorithm. All tumours were analysed with targeted next-generation sequencing ( NGS). Additionally, TP53 mutations were investigated with direct sequencing. In both cohorts, we observed a significant association between CD8+ TILs density and high PD-L1 IHC expression in tumour cells ( TCs). Furthermore, high SP142 PD-L1 expression in immune cells ( ICs) was also associated significantly with CD8+ TILs density. Therefore, CD8+ TILs density discriminated between patients with high versus low PD-L1 IHC expression with excellent sensitivity and specificity. Interestingly, the highest percentages of PD-L1-positive TCs with the three antibodies were found in samples with cyclin-dependent kinase 6 ( CDK6) amplification, with high amplification of proto-oncogene C-Myc ( CMYC) or with cyclin D1- PI3 kinase subunit alpha ( CCND1- PIK3 CA) co-amplification. High SP142 PD-L1 IHC expression in ICs showed a non-significant correlation with TP53 mutations. Conversely, most cases with fibroblast growth factor receptor 1 ( FGFR1) amplification were negative for all PD-L1 clones. Conclusions Our preliminary results support the use of digital CD8+ TILs scoring and targeted NGS alongside PD-L1 expression. The approach presented herein could help define patients with SCCs candidates to immune checkpoints inhibitors. [ABSTRACT FROM AUTHOR]

• GRAVID reports one of the largest series of patients with lung cancer and COVID-19. • Of 447 patients, 78 % were hospitalized, 2% were admitted to ICU and 33 % died. • Mortality was higher in patients who received corticosteroids at hospitalization. • Anticancer therapy was not associated with increased risk of death. • Individual risks and benefits should be considered in management of these patients. Patients with cancer may be at increased risk of more severe COVID-19 disease; however, prognostic factors are not yet clearly identified. The GRAVID study aimed to describe clinical characteristics, outcomes, and predictors of poor outcome in patients with lung cancer and COVID-19. Prospective observational study that included medical records of patients with lung cancer and PCR-confirmed COVID-19 diagnosis across 65 Spanish hospitals. The primary endpoint was all-cause mortality; secondary endpoints were hospitalization and admission to intensive care units (ICU). A total of 447 patients with a mean age of 67.1 ± 9.8 years were analysed. The majority were men (74.3 %) and current/former smokers (85.7 %). NSCLC was the most frequent type of cancer (84.5 %), mainly as adenocarcinoma (51.0 %), and stage III metastatic or unresectable disease (79.2 %). Nearly 60 % of patients were receiving anticancer treatment, mostly first-line chemotherapy. Overall, 350 (78.3 %) patients were hospitalized for a mean of 13.4 ± 11.4 days, 9 (2.0 %) were admitted to ICU and 146 (32.7 %) died. Advanced disease and the use of corticosteroids to treat COVID-19 during hospitalization were predictors of mortality. Hospitalized, non-end-of-life stage patients with lymphocytopenia and high LDH had an increased risk of death. Severity of COVID-19 correlated to higher mortality, ICU admission, and mechanical ventilation rates. Mortality rate was higher among patients treated with corticosteroids during hospitalization, while anticancer therapy was not associated with an increased risk of hospitalization or death. Tailored approaches are warranted to ensure effective cancer management while minimizing the risk of exposure to SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Introduction: Clear cell sarcoma (CCS) is a rare and aggressive soft tissue sarcoma. CCS is characterized by the translocation t(12;22) (q13;q12), involving the fusion of EWSR1 and ATF1 genes, and less frequently the fusion gene EWSR1-CREB1. Usually, CCSs are considered poorly responsive to conventional chemotherapy. However, trabectedin has shown activity against translocation-related sarcomas. Furthermore, preclinical results suggest that trabectedin is a promising antitumor agent for CCS, potentially inducing melanocytic differentiation. Case Presentation: We report the case of a challenging anatomopathological diagnosis in a patient with an aggressive metastatic CCS. Following the diagnosis of CCS, the patient experienced a clinical and radiological tumor response to trabectedin after four lines of treatment. Conclusion: This is a novel report of CCS treated with trabectedin that resulted in a partial response and suggests the need for further research on trabectedin as a therapeutic option for CCS. [ABSTRACT FROM AUTHOR]

PURPOSE: Patients with cancer are at increased risk of severe COVID-19 disease, but have heterogeneous presentations and outcomes. Decision-making tools for hospital admission, severity prediction, and increased monitoring for early intervention are critical. We sought to identify features of COVID-19 disease in patients with cancer predicting severe disease and build a decision support online tool, COVID-19 Risk in Oncology Evaluation Tool (CORONET). METHODS: Patients with active cancer (stage I-IV) and laboratory-confirmed COVID-19 disease presenting to hospitals worldwide were included. Discharge (within 24 hours), admission (≥ 24 hours inpatient), oxygen (O2) requirement, and death were combined in a 0-3 point severity scale. Association of features with outcomes were investigated using Lasso regression and Random Forest combined with Shapley Additive Explanations. The CORONET model was then examined in the entire cohort to build an online CORONET decision support tool. Admission and severe disease thresholds were established through pragmatically defined cost functions. Finally, the CORONET model was validated on an external cohort. RESULTS: The model development data set comprised 920 patients, with median age 70 (range 5-99) years, 56% males, 44% females, and 81% solid versus 19% hematologic cancers. In derivation, Random Forest demonstrated superior performance over Lasso with lower mean squared error (0.801 v 0.807) and was selected for development. During validation (n = 282 patients), the performance of CORONET varied depending on the country cohort. CORONET cutoffs for admission and mortality of 1.0 and 2.3 were established. The CORONET decision support tool recommended admission for 95% of patients eventually requiring oxygen and 97% of those who died (94% and 98% in validation, respectively). The specificity for mortality prediction was 92% and 83% in derivation and validation, respectively. Shapley Additive Explanations revealed that National Early Warning Score 2, C-reactive protein, and albumin were the most important features contributing to COVID-19 severity prediction in patients with cancer at time of hospital presentation. CONCLUSION: CORONET, a decision support tool validated in health care systems worldwide, can aid admission decisions and predict COVID-19 severity in patients with cancer. CORONET, a tool to aid admission decisions for patients with cancer + COVID-19 disease and predict its severity. [ABSTRACT FROM AUTHOR]

The discovery of oncogenic driver mutations and the subsequent developments in targeted therapies have led to improved outcomes for subsets of lung cancer patients. The identification of additional oncogenic and drug-sensitive alterations may similarly lead to new therapeutic approaches for lung cancer. We identify and characterize novel FGFR2 extracellular domain insertion mutations and demonstrate that they are both oncogenic and sensitive to inhibition by FGFR kinase inhibitors. We demonstrate that the mechanism of FGFR2 activation and subsequent transformation is mediated by ligand-independent dimerization and activation of FGFR2 kinase activity. Both FGFR2-mutant forms are predominantly located in the endoplasmic reticulum and Golgi but nevertheless can activate downstream signaling pathways through their interactions with fibroblast growth factor receptor substrate 2 (FRS2). Our findings provide a rationale for therapeutically targeting this unique subset of FGFR2-mutant cancers as well as insight into their oncogenic mechanisms. [ABSTRACT FROM AUTHOR]

Glomus tumors (GT) are very rare mesenchymal neoplasms arising from glomus bodies, arteriovenous structures located in the dermis and involved in thermoregulation. Although most are benign, they may occasionally present malignant histological features associated with aggressive clinical behavior, metastatic spread, and poor response to conventional chemotherapy. The BRAF V600E mutation has been identified in a subset of malignant GT, highlighting a promising therapeutic target. Here, we report the impressive clinical and morpho-metabolic response of a metastatic BRAF V600E-mutated glomangiosarcoma after treatment with encorafenib and binimetinib.

The year 2024 is the 20 th anniversary of the discovery of activating epidermal growth factor receptor ( EGFR ) mutations in non-small cell lung cancer (NSCLC). Since then, tremendous advances have been made in the treatment of NSCLC based on this discovery. Some of these studies have led to seismic changes in the concept of oncology research and spurred treatment advances beyond NSCLC, leading to a current true era of precision oncology for all solid tumors. We now routinely molecularly profile all tumor types and even plasma samples of patients with NSCLC for multiple actionable driver mutations, independent of patient clinical characteristics nor is profiling limited to the advanced incurable stage. We are increasingly monitoring treatment responses and detecting resistance to targeted therapy by using plasma genotyping. Furthermore, we are now profiling early-stage NSCLC for appropriate adjuvant targeted treatment leading to an eventual potential "cure" in early-stage EGFR+ NSCLC which have societal implication on implementing lung cancer screening in never-smokers as most EGFR+ NSCLC patients are never-smokers. All these advances were unfathomable in 2004 when the five papers that described "discoveries" of activating EGFR mutations (del19, L858R, exon 20 insertions, and "uncommon" mutations) were published. To commemorate this 20 th anniversary, we assembled a global panel of thoracic medical oncology experts to select the top 20 papers (publications or congress presentation) from the 20 years since this seminal discovery with December 31, 2023 as the cutoff date for inclusion of papers to be voted on. Papers ranked 21 to 30 were considered "honorable mention" and also annotated. Our objective is that these 30 papers with their annotations about their impact and even all the ranked papers will serve as "syllabus" for the education of future thoracic oncology trainees. Finally, we mentioned potential practice-changing clinical trials to be reported. One of them, LAURA was published online on June 2, 2024 was not included in the list of papers to be voted on but will surely be highly ranked if this consensus survery is performed again on the 25 th anniversay of the discovery EGFR mutations (i.e. top 25 papers on the 25 years since the discovery of activating EGFR mutations)., Competing Interests: Dr Sai-Hong Ou reports grants, personal fees from Pfizer, Jansen, Daiichi Sankyo; personal fees from Anheart Therapeutics, Bayer, Dava Oncology LLP, OncLive, BMS; grants from Revolution Medicines, Mirati, Merus; grants and/or stock ownership from Nuvalent, MBrace Therapeutics, BlossomHill Therapeutics, Turning Point Therapeutics, Elevation Oncology, and Lilly, outside the submitted work. Dr Xiuning Le reports personal fees from AstraZeneca, EMD Serono, Lilly, Boehringer Ingelheim, Regeneron, Bayer, Teligene, SystImmune, Janssen, Daiichi, AbbVie, ArriVent, and Abion, outside the submitted work. Dr Misako Nagasaka reports personal fees from AstraZeneca, Daiichi Sankyo, Novartis, EMD Serono, Pfizer, Lilly, Genentech, Regeneron, BMS, Caris Life Sciences, Mirati, Takeda, Janssen, Blueprint Medicine; non-financial support from AnHeart Therapeutics, outside the submitted work. Dr Thanyanan Reungwetwattana reports grants, personal fees from AstraZeneca, Roche, Novartis, MSD, Yuhan; personal fees from Pfizer, J&J, BMS, and Amgen, outside the submitted work. Prof. Dr. Myung-Ju Ahn reports personal fees from AstraZeneca, Yuhan, TAKEDA, Daiichi Sankyo, Alpha pharmaceuticals, Merck, Amgen, MSD, Roche, and voronoi, outside the submitted work. Dr Edgardo Santos reports personal fees from AstraZeneca, Genentech, Sanofi, Regeneron, AbbVie, Novartis, Amgen, Boehringer-Ingelheim, BMS, Eli Lilly, EMD Serono, G1 Therapeutics, Jazz Pharmaceuticals, Merck, Mirati, Pfizer, Coherus, Sobi, Takeda, and Johnson and Johnson, during the conduct of the study. Dr Elaine Shum reports personal fees from AstraZeneca, Johnson & Johnson, Genentech, Regeneron, Gilead, Bristol Meyers Squibb, Boehringer Ingelheim; grants from Delfi Diagnostics, outside the submitted work. Dr Antonio Calles reports personal fees, grants and/or non-financial support from AstraZeneca, Amgen, Boehringer-Ingelheim, Bayer, Pfizer, Roche, MSD, BMS, Novartis, Lilly, Takeda, and PharmaMar. Dr Gilberto Lopes reports stock ownership from Lucence Diagnostics, Xilis, Biomab, Morphometrix, and CDR-Life; honoraria from Boehringer Ingelheim, Blueprint Medicines, AstraZeneca, Merck, and Janssen; consulting or advisory role for Pfizer and AstraZeneca; research funding from AstraZeneca, Lucence, Xilis, E.R. Squibb Sons, LLC; research funding to his institution from Merck Sharp & Dohme, EMD Serono, AstraZeneca, Blueprint Medicines, Tesaro, Bavarian Nordic, NOVARTIS, G1 Therapeutics, adaptimmune, BMS, GSK, AbbVie, Rgenix, Pfizer, Roche, Genentech, Lilly, Janssen; travel, accommodations and expenses from Boehringer Ingelheim, Pfizer, E.R. Squibb Sons, LLC, Janssen, Seattle Genetics, Celgene, Ibsen, Pharmacyclics, Merck, AstraZeneca, Seagen; and Mirati Therapeutics. Dr Junko Tanizaki reports personal fees from AstraZeneca K.K., Boehringer-Ingelheim Japan Inc., Bristol-Myers Squibb Co. Ltd., Chugai Pharmaceutical Co., Ltd., Daiichi sankyo Co., Ltd, Eli Lilly Japan K.K., Janssen Pharmaceutical K.K., MSD K.K., Nihon Medi-Physics Co., Ltd, Nippon Kayaku Co., Ltd., Taiho Pharmaceutical Co. Ltd. K., Ono pharmaceutical Co. Ltd., and Pfizer Japan Inc., outside the submitted work. Dr Hidehito Horinouchi reports grants and/or personal fees from Roche/Chugai, AstraZeneca, BMS/ONO, AbbVie, Daiichi-Sankyo, Kyowa-Kirin, Taiho, and Guardant, outside the submitted work. Dr Marina Garassino reports personal fees from AstraZeneca, during the conduct of the study. Professor Sanjay Popat reports personal fees from Ahneart, Amgen, AstraZeneca, Bayer, Blueprint, BMS, Boehringer Ingelheim, Daiichi Sankyo, Ellipses, EQRx, GlaxoSmithKline, Guardant Health, Janssen, Lilly, Merck KGaA, Mirati, MSD, Novocure, Novartis, Pfizer, PharmaMar, Pierre Fabre, Roche, Sanofi, Takeda, and Turning Point Therapeutics, during the conduct of the study. Professor Benjamin Besse is advisory board of Daiichi Sankyo, F. Hoffmann-La Roche Ltd, steering committee of and counsel for Janssen, Taiho, AstraZeneca, and Takeda, during the conduct of the study. Dr Ross Soo reports grants and/or personal fees from Bayer, AbbVie, Amgen, Astra-Zeneca, BMS, Boehringer Ingelheim, Daiichi Sankyo, J INTS BIO, Janssen, Lily, Merck, Merck Serono, Novartis, Pfizer, Puma, Roche, Sanofi, Taiho, Takeda, ThermoFisher, and Yuhan, outside the submitted work. The authors report no other conflicts of interest in this work., (© 2024 Ou et al.)