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Purpose: Mechanisms of primary resistance to inhibitors of the programmed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) signaling axis in non-small cell lung cancer (NSCLC) are still poorly understood. While some studies suggest the involvement of trophoblast cell surface antigen 2 (TROP2) in modulating tumor cell resistance to therapeutic drugs, its specific role in the context of PD-1/PD-L1 axis blockade is not definitively established., Experimental Design: We performed high-throughput analysis of transcriptomic data from 891 NSCLC tumors from patients treated with either the PD-L1 inhibitor atezolizumab or chemotherapy in two large randomized clinical trials. To confirm our results at the protein level, we complemented this transcriptional approach by performing a multiplex immunofluorescence analysis of tumor tissue samples as well as a proteomic profiling of plasma., Results: We observed a significant association of TROP2 overexpression with worse progression-free survival and overall survival on PD-L1 blockade, independent of other prognostic factors. Importantly, we found increased TROP2 expression to be predictive of survival in patients treated with atezolizumab but not chemotherapy. TROP2 overexpression was associated with decreased T-cell infiltration. We confirmed these results at the proteomic level both on tumor tissue and in plasma., Conclusions: Our results suggest an important contribution of TROP2 expression to the primary resistance to PD-L1 blockade in NSCLC. TROP2-biomarker-based strategy may be relevant in selecting patients with NSCLC who are more likely to benefit from a combination of immunotherapy and an anti-TROP2 agent., (©2023 The Authors; Published by the American Association for Cancer Research.)

Purpose: Overexpression of the tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase 1 (IDO1) has been reported in several tumor types, including non-small cell lung cancer (NSCLC), and has been shown to promote tumor-immune evasion and inhibit T-cell activation through increased tryptophan degradation and the production of several immunosuppressive metabolites collectively known as kynurenines. However, it remains unclear whether IDO1 expression by tumor cells is detrimental specifically in the context of programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) axis blockade., Experimental Design: We analyzed the transcriptome of 891 NSCLC tumor samples from patients enrolled in two large randomized clinical trials investigating the safety and activity of atezolizumab, a humanized IgG1 mAb that targets PD-L1, versus docetaxel in patients with advanced NSCLC. We complemented these transcriptomics results at the protein level by using multiplex immunofluorescence and at the functional level with in vitro experiments., Results: The increased expression of the tryptophan-catabolizing enzyme IDO1 was significantly associated with improved objective response, progression-free survival, and overall survival in patients treated with PD-L1 inhibitors, but not in those treated with chemotherapy. Strikingly, inflamed tumors had higher levels of IDO1, and IDO1 was also expressed in tertiary lymphoid structures (TLS) by mature follicular dendritic cells. L-kynurenine impaired the differentiation of antibody-producing B cells induced by follicular helper T (Tfh)/B-cell interactions, a hallmark process within TLS., Conclusions: IDO1 pathway in NSCLC is driven by the immune system rather than by tumor cells. Targeting IDO1 in combination with anti-PD-1/PD-L1 might be beneficial only in patients with inflamed tumors and particularly in those bearing TLS., (©2023 The Authors; Published by the American Association for Cancer Research.)

Introduction: Integrating telemedicine into cancer care remains a major challenge. There are little clinical evidence for teleconsultation efficacy and safety in daily oncology practice. This study as a pioneering experience, aimed to analyze patient and physician opinions regarding the implementation of telemedicine consultations, and to identify major limitations of telehealth spread in an oncology institute., Material and Methods: During COVID-19 lockdown, patients and physicians who took part to at least one video-based teleconsultation between March and May 2020, were enrolled in this observational study. All eligible patients received an anonymous online questionnaire. On the other hand, all physicians eligible to participate were asked through email to complete a questionnaire., Results: In this study, 31 physicians and 304 patients consented to participate in this study by answering the questionnaire and were included. Regarding telemedicine satisfaction, 65.8% of patients were satisfied. The lack of clinical examination was the major limitation reported by 77% of patients. Patients belonging to a high socio-professional category were statistically more dissatisfied with the relationship with their doctor (OR = 2.31 and 95% CI [1.12; 4.74])., Conclusion: This study showed promising results of incorporating video-based teleconsultations into cancer patient management. Randomized clinical trials are needed in order to accelerate the digital implementation in clinical practice.

Purpose: Targeted therapies (TT) and immune checkpoint blockers (ICB) have revolutionized the approach to non-small cell lung cancer (NSCLC) treatment in the era of precision medicine. Their impact as switch maintenance therapy based on molecular characterization is unknown., Patients and Methods: SAFIR02-Lung/IFCT 1301 was an open-label, randomized, phase II trial, involving 33 centers in France. We investigated eight TT (substudy-1) and one ICB (substudy-2), compared with standard-of-care as a maintenance strategy in patients with advanced EGFR, ALK wild-type (wt) NSCLC without progression after first-line chemotherapy, based on high-throughput genome analysis. The primary outcome was progression-free survival (PFS)., Results: Among the 175 patients randomized in substudy-1, 116 received TT (selumetinib, vistusertib, capivasertib, AZD4547, AZD8931, vandetanib, olaparib, savolitinib) and 59 standard-of-care. Median PFS was 2.7 months [95% confidence interval (CI), 1.6-2.9] with TT versus 2.7 months (1.6-4.1) with standard-of-care (HR, 0.97; 95% CI, 0.7-1.36; P = 0.87). There were no significant differences in PFS within any molecular subgroup. In substudy-2, 183 patients were randomized, 121 received durvalumab and 62 standard-of-care. Median PFS was 3.0 months (2.3-4.4) with durvalumab versus 3.0 months (2.0-5.1) with standard-of-care (HR, 0.86; 95% CI, 0.62-1.20; P = 0.38). Preplanned subgroup analysis showed an enhanced benefit with durvalumab in patients with PD-L1 tumor proportion score (TPS) ≥1%, (n = 29; HR, 0.29; 95% CI, 0.11-0.75) as compared with PD-L1 <1% (n = 31; HR, 0.71; 95% CI, 0.31-1.60; Pinteraction = 0.036)., Conclusions: Molecular profiling can feasibly be implemented to guide treatment choice for the maintenance strategy in EGFR/ALK wt NSCLC; in this study it did not lead to substantial treatment benefits beyond durvalumab for PD-L1 ≥ 1 patients., (©2022 American Association for Cancer Research.)

Background: The high sensitivity of PET-CT can identify hypermetabolic mediastinal adenopathies during cancer management, but specificity is low and a biopsy is sometimes required to eliminate benign adenopathies., Methods: This prospective diagnostic accuracy study included patients with hypermetabolic mediastinal lymphadenopathies revealed on PET-CT during either the initial management of a cancer, treatment evaluation, or monitoring. All patients underwent EUS-FNA. Diagnoses of malignancy based on cytological analysis following EUS-FNA were compared with clinical and radiological follow-up information. The treatment strategy decided before the results of the EUS-FNA pathology reports (Multidisciplinary Team Meeting [MTM-1]) was recorded and compared to the treatment strategy decided once pathological data from EUS-FNA were available (MTM-2)., Main Findings: Between 2013 and 2018, 75 patients were included with 47 eligible and evaluable patients. Sensitivity, specificity, and positive and negative predictive values of EUS-FNA were 93%, 100%, 100% and 90%, respectively. The concordance value between the therapeutic strategies determined for MTM-1 and MTM-2 was 44.7%. There were no significant differences in the intensity of fixation on PET-CT between malignant and benign lesions., Conclusion: The diagnostic accuracy of the minimally invasive EUS-FNA procedure is sufficiently robust to avoid the need for diagnostic surgery. The combination of PET-CT and EUS-FNA may alter the therapeutic strategy that would be considered after PET-CT alone., Registration: NCT01892501., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Only a minority of patients derive long-term clinical benefit from anti-PD1/PD-L1 monoclonal antibodies. The presence of tertiary lymphoid structures (TLS) has been associated with improved survival in several tumor types. Here, using a large-scale retrospective analysis of three independent cohorts of cancer patients treated with anti-PD1/PD-L1 antibodies, we showed that the presence of mature TLS was associated with improved objective response rate, progression-free survival, and overall survival independently of PD-L1 expression status and CD8+ T-cell density. These results pave the way for using TLS detection to select patients who are more likely to benefit from immune checkpoint blockade., Competing Interests: DECLARATION OF INTERESTS LV, MB, SC, SLM, ML, IS, MT, GR, SP, MC, FC, CL, KB, MK, IG, CSF, VV, FC, WHF, and FLL: Nothing to disclose AB, JPG, and CR: Employees of Immusmol/Explicyte EO, AS: Employees of Astra Zeneca AI: Received research grants from Astra Zeneca, Bayer, BMS, Chugai, Merck, MSD, Pharmamar, Novartis, Roche, and received personal fees from Epizyme, Bayer, Lilly, Roche, and Springworks BB: Received grants from AstraZeneca , Pfizer , Eli Lilly , Onxeo , Bristol Myers Squibb , Inivata , Abbvie , Amgen , Blueprint Medicines , Celgene , GlaxoSmithKline , Ignyta , Ipsen , Merck KGaA , MSD Oncology , Nektar , PharmaMar , Sanofi , Spectrum Pharmaceuticals , Takeda , Tiziana Therapeutics , Cristal Therapeutics , Daiichi Sankyo , Janssen Oncology , OSE Immunotherapeutics , BeiGene , Boehringer Ingelheim , Genentech , SERVIER , Tolero Pharmaceuticals YL: Received grants and personal fees from Janssen, during the conduct of the study; personal fees and non-financial support from Astellas, grants and personal fees from Sanofi, personal fees and non-financial support from Roche, personal fees and non-financial support from AstraZeneca, grants, personal fees and non-financial support from MSD, personal fees and non-financial support from BMS, personal fees from Clovis , personal fees and non-financial support from Seattle Genetics, personal fees from Incyte, personal fees from Pfizer. AM: Received research grants from Mersu, Bristol-Myers Squibb, Boehringer Ingelheim, Transgene, MSD and received personal fees from Bristol-Myers Squibb, AstraZeneca, MedImmune, Oncovir, Merieux JCS: Has received consultancy fees from AstraZeneca, Astex, Clovis, GSK, GamaMabs, Lilly, MSD, Mission Therapeutics, Merus, Pfizer, Pharma Mar, Pierre Fabre, Roche/Genentech, Sanofi, Servier, Symphogen, and Takeda.

Non-small-cell lung carcinoma is a frequent type of lung cancer with a bad prognosis. Depending on the stage and genomics, several therapeutical approaches are used. Tyrosine Kinase Inhibitors (TKI) may be successful for a time in the treatment of EGFR-mutated non-small cells lung carcinoma. Our objective is here to introduce a survival assessment as their efficacy in the long run is challenging to evaluate. The study includes 17 patients diagnosed with EGFR-mutated non-small cell lung cancer and exposed to an EGFR-targeting TKI with 3 computed tomography (CT) scans of the primary tumor (one before the TKI introduction and two after). An imaging biomarker based on evolution of texture heterogeneity between the first and the third exams is derived and computed from a mathematical model and patient data. Defining the overall survival as the time between the introduction of the TKI treatment and the patient death, we obtain a statistically significant correlation between the overall survival and our imaging marker ([Formula: see text]). Using the ROC curve, the patients are separated into two populations and the comparison of the survival curves is statistically significant ([Formula: see text]). The baseline exam seems to have a significant role in the prediction of response to TKI treatment. More precisely, our imaging biomarker defined using only the CT scan before the TKI introduction allows to determine a first classification of the population which is improved over time using the imaging marker as soon as more CT scans are available. This exploratory study leads us to think that it is possible to obtain a survival assessment using only few CT scans of the primary tumor.

Non-small cell lung cancer (NSCLC) remains the leading cause of cancer death; percutaneous thermal ablation (TA) has proven feasibility, good local control and good tolerance in stage I tumors for patients with medical comorbidities and who are ineligible for surgery. In this context, stereotactic body radiotherapy (SBRT) has demonstrated high efficacy in treating T1 NSCLC and will need to be compared with percutaneous ablation. TA is also indicated in oligoprogressive disease; and can be proposed as a salvage treatment option for tumor recurrence after radiotherapy. Besides more advanced NSCLC could be also an indication of TA in combination with systemic treatments. A large majority of diagnosed NSCLC do not exhibit specific targetable genetic aberration. Those tumors present poorer prognosis and have been treated with standard chemotherapy regimen until the recent development of immune checkpoint inhibitors (ICIs) based immunotherapy. Combining TA with immunotherapy is promising and still needs to be explored.

Purpose: To evaluate the survival outcomes of percutaneous thermal ablation (RFA + microwaves) for patients presenting N0 non-small-cell lung cancer (NSCLC) ineligible for surgery., Materials and Methods: Eighty-seven patients from two comprehensive cancer centers were included. Eighty-two patients were treated with RFA electrodes and five with microwave antenna. Overall survival (OS) and disease-free survival (DFS) were estimated and predictive factors of local tumor progression, OS and DFS identified and compared by univariate and multivariate analyses, Results: Median follow-up was 30.5 months (interquartile range 16.7-51) and tumor size was 21 mm (range 10-54 mm). Treatment was incomplete for 14 patients with a local tumor progression of 11.5, 18.3, and 21.1 % at 1, 2, and 3 years, respectively. Two patients presented with neurological (grade III or IV) complications, and one died of respiratory and multivisceral failure as a result of the procedure at 29 days. In univariate analysis, increasing tumor size (P = 0.003) was the only predictive factor related to risk of local tumor progression. 5-year OS and DFS were 58.1 and 27.9 %, respectively. Sex (P = 0.044), pathology (P = 0.032), and tumor size >2 cm (P = 0.046) were prognostic factors for DFS. In multivariate analysis, pathology (P = 0.033) and tumor size >2 cm (P = 0.032) were independent prognostic factors for DFS., Conclusions: Oversized and overlapping ablation of N0 NSCLC was well tolerated, effective, with few local tumor progressions, even over long-term follow-up. Increasing tumor size was the main prognostic factor linked to OS, DFS, and local tumor progression.

Objective: We tested the effect of dietary advice dedicated to increase intake in older patients at risk for malnutrition during chemotherapy, versus usual care, on one-year mortality., Method: We conducted a multicentre, open-label interventional, stratified (centre), parallel randomised controlled trial, with a 1∶1 ratio, with two-year follow-up. Patients were aged 70 years or older treated with chemotherapy for solid tumour and at risk of malnutrition (MNA, Mini Nutritional Assessment 17-23.5). Intervention consisted of diet counselling with the aim of achieving an energy intake of 30 kCal/kg body weight/d and 1.2 g protein/kg/d, by face-to-face discussion targeting the main nutritional symptoms, compared to usual care. Interviews were performed 6 times during the chemotherapy sessions for 3 to 6 months. The primary endpoint was 1-year mortality and secondary endpoints were 2-year mortality, toxicities and chemotherapy outcomes., Results: Between April 2007 and March 2010 we randomised 341 patients and 336 were analysed: mean (standard deviation) age of 78.0 y (4·9), 51.2% male, mean MNA 20.2 (2.1). Distribution of cancer types was similar in the two groups; the most frequent were colon (22.4%), lymphoma (14.9%), lung (10.4%), and pancreas (17.0%). Both groups increased their dietary intake, but to a larger extent with intervention (p<0.01). At the second visit, the energy target was achieved in 57 (40.4%) patients and the protein target in 66 (46.8%) with the intervention compared respectively to 13 (13.5%) and 20 (20.8%) in the controls. Death occurred during the first year in 143 patients (42.56%), without difference according to the intervention (p = 0.79). No difference in nutritional status changes was found. Response to chemotherapy was also similar between the groups., Conclusion: Early dietary counselling was efficient in increasing intake but had no beneficial effect on mortality or secondary outcomes. Cancer cachexia antianabolism may explain this lack of effect., Trial Registration: ClinicalTrials.gov NCT00459589.

Mediastinal lymphadenopathy may be detected by CT-scan or positron emission tomography. Malignant (e.g, lung cancer, metastatic cancer, lymphoma), infectious (e.g, tuberculosis, histoplasmosis), and systemic processes (e.g, sarcoidosis) can cause mediastinal adenopathy. In the posterior and inferior mediastinum, endoscopic ultrasound visualizes and directs transesophageal fine needle aspiration of adenopathy. In the anterior mediastinum, endobronchial ultrasound visualizes and directs transbronchial fine needle aspiration of adenopathy. We discuss the role of EUS and EBUS in the evaluation of mediastinal adenopathy according to their anatomical localization.

Radiofrequency (RF) ablation is a technique of thermotherapy which emerged over the last fifteen years in the field of oncology. RF directed toward a specific tumor mass is known to be very effective (over 90%) for treating tumors less than 2.5 cm. RF is used for patients with early-stage lung or liver cancers who are not surgical candidates, With improvements in systemic therapy, increasing interest in the use of local therapy for metastases has arisen. Eradication of residual metastases via local therapies has a sense in patients with stabilized disease. Nonsurgical alternative like RF has become popular because it is less invasive than surgery and has demonstrated great efficiency. Nevertheless prospective randomized trials to compare RF with surgery are difficult to achieve, prospective studies are needed to better evaluate the technique.

The novel nucleoside agent gemcitabine has demonstrated antitumor activity against a variety of solid tumors and is associated with low toxicity. A phase I trial in Germany of gemcitabine combined with the alkylating agent ifosfamide has shown encouraging activity against non-small cell lung cancer. The efficacy and toxicity of this combination was further evaluated in a phase II trial involving chemotherapy-naive patients with non-small cell lung cancer (mostly stage IV disease). Gemcitabine was administered at a dose of 1,000 mg/m2 on days 1, 8, and 15, followed by a 1-week rest, while ifosfamide was given at a dose of 1,500 mg/m2 on days 8 through 12. Fifty-five patients were treated, 49 of whom are evaluable for response. Six patients were not evaluable because they had not received sufficient therapy (less than one complete cycle) because of early disease progression or early death. Twelve patients responded, for an overall objective response rate of 24.5%. The median survival time was 8.9 months, and the 1-year survival rate was 30.9%. Grades 3 and 4 neutropenia occurred in 30.2% and 24.5% of patients, respectively, but the incidence of infection was low. These results indicate that the combination of gemcitabine and ifosfamide is active against non-small cell lung cancer and has a mild toxicity profile, and suggest that further evaluation of this combination is warranted.