Use of non-small cell lung cancer multicellular tumor spheroids to study the impact of chemotherapy.

BACKGROUND: Lung cancers represent the main cause of cancer related-death worldwide. Recently, immunotherapy alone or in combination with chemotherapy has deeply impacted the therapeutic care leading to an improved overall survival. However, relapse will finally occur, with no efficient second line treatment so far. New therapies development based on the comprehension of resistance mechanisms is necessary. However, the difficulties to obtain tumor samples before and after first line treatment hamper to clearly understand the consequence of these molecules on tumor cells and also to identify adapted second line therapies. METHODS: To overcome this difficulty, we developed multicellular tumor spheroids (MCTS) using characterized Non-Small Cell Lung Cancer (NSCLC) cell lines, monocytes from healthy donors and fibroblasts. MCTS were treated with carboplatin-paclitaxel or -gemcitabine combinations according to clinical administration schedules. The treatments impact was studied using cell viability assay, histological analyses, 3'RNA sequencing, real-time PCR, flow cytometry and confocal microscopy. RESULTS: We showed that treatments induced a decrease in cell viability and strong modifications in the transcriptomic profile notably at the level of pathways involved in DNA damage repair and cell cycle. Interestingly, we also observed a modification of genes expression considered as hallmarks of response to immune check point inhibitors and immunogenicity, particularly an increase in CD274 gene expression, coding for PD-L1. This result was validated at the protein level and shown to be restricted to tumor cells on MCTS containing fibroblasts and macrophages. This increase was also observed in an additional cell line, expressing low basal CD274 level. CONCLUSIONS: This study shows that MCTS are interesting models to study the impact of first line therapies using conditions close to clinical practice and also to identify more adapted second line or concomitant therapies for lung cancer treatment.

[National survey of Advanced Practice Nurses in oncology-haematology: Evaluation of activity and continuing education]. / Enquête nationale auprès des infirmiers en pratique avancée mention oncologie-hématologie : évaluation de l'activité et de la formation continue.

INTRODUCTION: The number of Advanced Practice Nurses (APNs) has significantly increased in France since 2019, with the number of graduates expected to reach 1700 by the end of 2023, up from approximately 60. Fifteen percent of them specialize in oncology-hematology (APN-OH). Data on their activities, access to continuing education, and expectations are limited. METHODS: We conducted an observational study among practicing APN-OHs in France. A questionnaire was distributed from June to September 2023. RESULTS: Of the 55 responding APN-OHs, 78.3% worked in Cancer Centers or within University Hospital Centers. Their primary motivation for becoming APN-OH was to enhance their nursing practice and deepen their medical knowledge, with teaching and research interests remaining marginal. Their level of responsibility generally aligned with their expectations and the medical staff was perceived as supportive. The main challenges were of logistical and material nature. The heterogeneity in APN-OH training was seen as a limiting factor in the attractiveness of the profession. The most significant gaps in their education revolved around the lack of practical cases. CONCLUSION: This study highlights that the primary concern of APN-OHs is to strengthen their practical training. Medical personnel are perceived as supportive, but challenges related to working conditions and education persist. It is essential to consider these factors to support the deployment of APN-OHs across the country and improve ongoing education.

Biomarker and pharmacodynamic activity of the transforming growth factor-beta (TGFß) inhibitor SAR439459 as monotherapy and in combination with cemiplimab in a phase I clinical study in patients with advanced solid tumors.

SAR439459, a 'second-generation' human anti-transforming growth factor-beta (TGFß) monoclonal antibody, inhibits all TGFß isoforms and improves the antitumor activity of anti-programmed cell death protein-1 therapeutics. This study reports the pharmacodynamics (PD) and biomarker results from phase I/Ib first-in-human study of SAR439459 ± cemiplimab in patients with advanced solid tumors (NCT03192345). In dose-escalation phase (Part 1), SAR439459 was administered intravenously at increasing doses either every 2 weeks (Q2W) or every 3 weeks (Q3W) with cemiplimab IV at 3 mg/kg Q2W or 350 mg Q3W, respectively, in patients with advanced solid tumors. In dose-expansion phase (Part 2), patients with melanoma received SAR439459 IV Q3W at preliminary recommended phase II dose (pRP2D) of 22.5/7.5 mg/kg or at 22.5 mg/kg with cemiplimab 350 mg IV Q3W. Tumor biopsy and peripheral blood samples were collected for exploratory biomarker analyses to assess target engagement and PD, and results were correlated with patients' clinical parameters. SAR439459 ± cemiplimab showed decreased plasma and tissue TGFß, downregulation of TGFß-pathway activation signature, modulation of peripheral natural killer (NK) and T cell expansion, proliferation, and increased secretion of CXCL10. Conversion of tumor tissue samples from 'immune-excluded' to 'immune-infiltrated' phenotype in a representative patient with melanoma SAR439459 22.5 mg/kg with cemiplimab was observed. In paired tumor and plasma, active and total TGFß1 was more consistently elevated followed by TGFß2, whereas TGFß3 was only measurable (lower limit of quantitation ≥2.68 pg/mg) in tumors. SAR439459 ± cemiplimab showed expected peripheral PD effects and TGFß alteration. However, further studies are needed to identify biomarkers of response.

Biomarker-directed targeted therapy plus durvalumab in advanced non-small-cell lung cancer: a phase 2 umbrella trial.

For patients with non-small-cell lung cancer (NSCLC) tumors without currently targetable molecular alterations, standard-of-care treatment is immunotherapy with anti-PD-(L)1 checkpoint inhibitors, alone or with platinum-doublet therapy. However, not all patients derive durable benefit and resistance to immune checkpoint blockade is common. Understanding mechanisms of resistance-which can include defects in DNA damage response and repair pathways, alterations or functional mutations in STK11/LKB1, alterations in antigen-presentation pathways, and immunosuppressive cellular subsets within the tumor microenvironment-and developing effective therapies to overcome them, remains an unmet need. Here the phase 2 umbrella HUDSON study evaluated rational combination regimens for advanced NSCLC following failure of anti-PD-(L)1-containing immunotherapy and platinum-doublet therapy. A total of 268 patients received durvalumab (anti-PD-L1 monoclonal antibody)-ceralasertib (ATR kinase inhibitor), durvalumab-olaparib (PARP inhibitor), durvalumab-danvatirsen (STAT3 antisense oligonucleotide) or durvalumab-oleclumab (anti-CD73 monoclonal antibody). Greatest clinical benefit was observed with durvalumab-ceralasertib; objective response rate (primary outcome) was 13.9% (11/79) versus 2.6% (5/189) with other regimens, pooled, median progression-free survival (secondary outcome) was 5.8 (80% confidence interval 4.6-7.4) versus 2.7 (1.8-2.8) months, and median overall survival (secondary outcome) was 17.4 (14.1-20.3) versus 9.4 (7.5-10.6) months. Benefit with durvalumab-ceralasertib was consistent across known immunotherapy-refractory subgroups. In ATM-altered patients hypothesized to harbor vulnerability to ATR inhibition, objective response rate was 26.1% (6/23) and median progression-free survival/median overall survival were 8.4/22.8 months. Durvalumab-ceralasertib safety/tolerability profile was manageable. Biomarker analyses suggested that anti-PD-L1/ATR inhibition induced immune changes that reinvigorated antitumor immunity. Durvalumab-ceralasertib is under further investigation in immunotherapy-refractory NSCLC.ClinicalTrials.gov identifier: NCT03334617.

A Multicenter Study Assessing the Real-World Use and Effectiveness of First-Line Chemotherapy Plus Immunotherapy in Advanced Small-Cell Lung Cancer (SCLC) Patients.

BACKGROUND: First-line chemotherapy plus immunotherapy (CT-IO) has recently demonstrated survival benefits over CT alone in extensive-stage small-cell lung cancer (ES-SCLC), based on randomized phase III studies. This retrospective multicenter study assessed the real-world use and effectiveness of CT-IO in ES-SCLC patients. PATIENTS AND METHODS: All newly diagnosed ES-SCLC patients from 4 French hospitals treated with CT alone or CT-IO between May 2020 and December 2021 were included. Overall survival (OS) and real-world progression-free survival (rwPFS) were estimated using the Kaplan-Meier method. Cox proportional hazard models were performed to estimate hazard ratios (HRs) with 95 % confidence intervals (CIs) in univariate and multivariate models. The aim was not to compare efficacy between groups. RESULTS: Among 104 patients, 75 (72.1%) received CT-IO. Brain metastases were diagnosed in 28.3% of patients, and 29.8% were performance status (PS) ≥ 2. At a median follow-up of 16.8 months (95%CI, 14.9-23.4), the median OS was 11.4 months (95%CI, 7.7-14.7) in the CT-IO group, and the 12-month OS rate was 43.6% (95%CI, 33.3-57.2). In the CT group, the median OS was 7.8 months (95%CI, 5.4-11.8) and the 12-month OS rate was 15.3% (95%CI, 5.7-41.0). In multivariate analyses, baseline brain and liver metastases were associated with a shorter OS for patients treated in the CT-IO group (HR, 3.80 [95%CI, 1.90-7.60] and 3.12 [95%CI, 1.60-6.08] respectively; P < 0.001 for both). CONCLUSION: We showed that clinicians have chosen to use IO beyond the specific criteria defined in guidelines. Survival data appeared promising with a median OS comparable to the one previously demonstrated in clinical trials.

Trastuzumab Deruxtecan in Patients With HER2-Mutant Metastatic Non-Small-Cell Lung Cancer: Primary Results From the Randomized, Phase II DESTINY-Lung02 Trial.

PURPOSE: Trastuzumab deruxtecan (T-DXd) 5.4 and 6.4 mg/kg showed robust antitumor activity in multiple cancer indications; however, T-DXd 5.4 mg/kg has not been evaluated in patients with previously treated human epidermal growth factor receptor 2-mutant (HER2m; defined as single-nucleotide variants and exon 20 insertions) metastatic non-small-cell lung cancer (mNSCLC). METHODS: DESTINY-Lung02, a blinded, multicenter, phase II study, investigated T-DXd 5.4 mg/kg once every 3 weeks for the first time in previously treated (platinum-containing therapy) patients with HER2m mNSCLC and further assessed T-DXd 6.4 mg/kg once every 3 weeks in this population. The primary end point was confirmed objective response rate (ORR) per RECIST v1.1 by blinded independent central review. RESULTS: One hundred fifty-two patients were randomly assigned 2:1 to T-DXd 5.4 or 6.4 mg/kg once every 3 weeks. As of December 23, 2022, the median duration of follow-up was 11.5 months (range, 1.1-20.6) with 5.4 mg/kg and 11.8 months (range, 0.6-21.0) with 6.4 mg/kg. Confirmed ORR was 49.0% (95% CI, 39.0 to 59.1) and 56.0% (95% CI, 41.3 to 70.0) and median duration of response was 16.8 months (95% CI, 6.4 to not estimable [NE]) and NE (95% CI, 8.3 to NE) with 5.4 and 6.4 mg/kg, respectively. Median treatment duration was 7.7 months (range, 0.7-20.8) with 5.4 mg/kg and 8.3 months (range, 0.7-20.3) with 6.4 mg/kg. Grade ≥ 3 drug-related treatment-emergent adverse events occurred in 39 of 101 (38.6%) and 29 of 50 (58.0%) patients with 5.4 and 6.4 mg/kg, respectively. 13 of 101 (12.9%) and 14 of 50 (28.0%) patients had adjudicated drug-related interstitial lung disease (2.0% grade ≥ 3 in each arm) with 5.4 and 6.4 mg/kg, respectively. CONCLUSION: T-DXd demonstrated clinically meaningful responses at both doses. Safety profile was acceptable and generally manageable, favoring T-DXd 5.4 mg/kg.

Impact of first-line immunotherapy on survival and intracranial outcomes in a cohort of non-small cell lung cancer patients with brain metastases at diagnosis.

BACKGROUND: Although brain metastases (BM) at diagnosis are common in non-squamous NSCLC patients (ns-NSCLC), they have been mostly excluded from randomized trials. The aim of this retrospective study was to evaluate real-word outcomes of frontline immune checkpoint inhibitor (ICI) in these patients. METHODS: Our study assess the intracranial and overall efficacy of first-line ICI-based therapy compared to chemotherapy (CT) in ns-NSCLC patients diagnosed with BM, showing no targetable alterations. Patients were divided according to systemic therapy: CT, ICI, or CT-ICI. Primary endpoint was overall survival (OS), compared using Kaplan-Meier and Cox methodology. Secondary endpoint was intracranial progression free survival (icPFS). RESULTS: Between 01 and 2018 and 05-2021, 118 patients were included (52 CT, 38 ICI and 28 CT-ICI). Median follow-up was 30.0 months. Intracranial radiotherapy was delivered for 75.0%, 68.4% and 67.9% of patients for CT, ICI and CT-ICI groups (p = 0.805). After adjustment, ICI and CT-ICI were associated with a better OS compared to CT (HR = 0.46, 95 %CI: 0.23-0.89, and HR = 0.52, 95 %CI: 0.27-1.01, respectively). ICI and CT-ICI were associated with a significant reduction in the risk of intracranial progression by 54% (HR = 0.46, 95 %CI: 0.25-0.84) and 59% (HR = 0.41, 95 %CI: 0.23-0.77) compared to CT. Stereotactic radiosurgery was associated with an increased icPFS compared to systemic therapy alone (HR = 0.51, 95% CI: 0.29 - 0.92), whereas whole-brain was not. CONCLUSIONS: Real-life ns-NSCLC patients with BM at diagnosis treated frontline with ICI presented OS and icPFS benefit compared to CT alone. A prospective assessment of the ideal type and sequence of systemic and local therapy should be conducted.

Early Locoregional Breast Surgery and Survival in de novo Metastatic Breast Cancer in the Multicenter National ESME Cohort.

OBJECTIVE: The aim was to evaluate the impact of local surgery performed during the year after MBC diagnosis on patients' outcomes from a large reallife cohort. SUMMARY BACKGROUND DATA: Locoregional treatment for patients with MBC at the time of diagnosis remains debated. METHODS: Women with newly diagnosed, de novo stage IV MBC and who started MBC treatment between January 2008 and December 2014 in one of the 18 French Comprehensive Cancer Centers were included (NCT03275311). The impact of local surgery performed during the first year on overall survival (OS) and progression-free survival (PFS) was evaluated by the Cox proportional hazards model in a 12 month-landmark analysis. RESULTS: Out of 16,703 patients in the ESME database, 1977 had stage IV MBC at diagnosis, were alive and progression-free at 12 months and eligible for this study. Among them, 530 (26.8%) had received primary breast cancer surgery within 12 months. A greater proportion of patients who received surgery had less than 3 metastatic sites than the no-surgery group (90.8% vs 78.2%, P < 0.0001). Surgery within 12 months was associated with treatment with chemotherapy, HER2-targeted therapy (89.1% vs 69.6%, P < 0.0001) and locoregional radiotherapy (81.7% vs 32.5%, P < 0.0001). Multivariable analyses showed that surgery performed within 12 months was associated with longer OS and PFS (adjusted HR [95%CI] = 0.75 [0.61-0.92] and 0.72 [0.63-0.83], respectively), which were also affected by pattern and number of metastatic sites, histological subtype, and age. CONCLUSIONS: In the large ESME cohort, surgery within 1 year after de novo MBC diagnosis was associated with a significantly better OS and PFS.

Prognostic Impact of TP53 Mutations in Metastatic Nonsquamous Non-small-cell Lung Cancer.

BACKGROUND: The prognostic impact of TP53 mutations in advanced or metastatic nonsquamous non-small-cell lung cancer (nsNSCLC) patients treated with chemotherapy and/or immune checkpoint inhibitors (ICI) remains unclear. MATERIALS AND METHODS: We retrospectively collected data from patients with nsNSCLC treated in the first line from January 2018 to May 2021. The patient was separated into 2 groups according to their TP53 mutation status (wt vs. mut). Survival was estimated through the Kaplan-Meier method and compared by log-rank test. RESULTS: Of 220 patients included, 126 were in the mutTP53 group, and 94 were in the wtTP53wt group. Median OS (mOS) was not significantly different between the mutTP53 and wtTP53 groups [17.5 months (95% confidence interval (CI), 11.3-21.5) vs. 9.5 months (95% CI, 7.4-14.2), (P = .051)]. In subgroup analyses, the mutTP53 group treated with ICI had a significantly improved mOS compared to the wtTP53 group [(24.7 months (95% CI, 20.8-not reach) vs. 12.0 months (95% CI, 4.7-not reach), (P = .017)] and mPFS [(9.6 months (95% CI, 5.8-not reach) vs. 3.2 months (95% CI, 1.3-13.8) (P = .048)]. There was no difference in terms of mOS and mPFS between the mutTP53 and the wtTP53 group treated by chemotherapy alone or combined with ICI. CONCLUSION: TP53 mutation had no survival impact in the overall population, but is associated with better outcomes with ICI alone. These results suggest that patients with TP53 mutations could be treated with ICI alone, and wild-type patients could benefit from the addition of chemotherapy.

Treatments for Non-Small-Cell Lung Cancer: The Multiple Options for Precision Medicine.

In recent years, advances in molecular diagnostics have transformed the management of advanced non-small-cell lung cancer (NSCLC), allowing for increasingly personalized approaches [...].

Treatment time interval in breast cancer: A population-based study on the impact of type and number of cancer centres attended.

OBJECTIVES: We studied both the independent and combined effects of the places of biopsy and treatment on the treatment time interval based on a population-based study. METHODS: We analysed the proportion of patients having a treatment time interval higher than the EUSOMA recommendation of 6 weeks, as a function of the number and the type of care centres the patients attended, from a French population-based regional cohort of women treated in 2015 for an incident invasive non-metastatic cancer (n = 505). RESULTS: About 33% [95% CI: 27; 38] of patients had a treatment time interval higher than 6 weeks. About 48% of the patients underwent their biopsy and their initial treatment in the different centres. Results from multivariable analyses supported the impact of the type and number of centres attended on the proportion of time intervals over 6 weeks. This proportion was higher among patients with biopsy and treatment in different centres and among patients treated in a university hospital. CONCLUSION: We pointed out the independent impact of the type and the number of care centres the patients attended, from biopsy to first treatment, on the treatment time interval, which is a well-known prognosis factor.

A fatal case associated with Catabacter hongkongensis bacteremia in lung cancer patient: A case report.

Catabacter hongkongensis is a bacterium first isolated in 2007 and has since been detected in the blood of about fifteen patients with disease such as gastrointestinal malignancy, intestinal obstruction, or acute intestinal infection. We describe herein the case of a patient newly diagnosed with metastatic lung cancer, who died from a fatal infection possibly related to Catabacter hongkongensis bacteremia. By reviewing all cases reported in the literature, our case report supports that this infection is associated with a very high mortality in cancer patients.

HRAS Q61L Mutation as a Possible Target for Non-Small Cell Lung Cancer: Case Series and Review of Literature.

INTRODUCTION: Assessment of actionable gene mutations and oncogene fusions have made a paradigm shift in treatment strategies of non-small cell lung cancer (NSCLC). HRAS mutations involved around 0.2-0.8% of NSCLC patients, mostly on codon 61. For these patients, few data are available regarding clinical characteristics and response to therapies. METHODS: Next-Generation Sequencing (NGS) done routinely at Nantes University Hospital was used to identify HRAS molecular alterations in NSCLC patients. We identified and described four HRAS p.GlnQ61Leu mutated patients. Literature of previously HRAS-mutant NSCLC cases was reviewed, and available data in solid tumour with the most advanced H-Ras specific inhibitor, tipifarnib, were presented. RESULTS: Of 1614 patients diagnosed with advanced NSCLC from January 2018 to December 2020, four (0.25%) had HRAS p.Gln61Leu mutation. Three of them died during the first-line systemic therapy. Furthermore, three additional cases were identified in literature. All cases were current or former smokers, most of them had pleural or pericardial effusion at diagnosis. CONCLUSIONS: The clinical course of patients with HRAS-mutant NSCLC remains unclear. Furthers cases should be identified in order to clarify prognosis and response to therapies. Tipifarnib, a farnesyl transferase inhibitor, is a promising candidate to target HRAS-mutant tumours and should be explored in NSCLC patients.

[Re-visiting the Pronopall score ten years later: A multicenter retrospective study]. / Réévaluation du score Pronopall : une étude rétrospective multicentrique.

INTRODUCTION: The Pronopall score, which distinguishes 3 prognostic groups in patients with advanced cancer, was initially proposed in 2008 and validated in a study published in 2018 but including patients between 2009 and 2010. Since the last decade, cancer management and therapeutic options have progressed. The objective of this study was to confirm the value of this score in patients with digestive and thoracic cancer. METHODS: From July 2019 to November 2020, this retrospective multi-center study included patients with digestive or thoracic cancers who fulfilled the same inclusion criteria as those used in the initial study, and in whom the Pronopall score could be calculated using its four variables (albumin serum level, LDH level, ECOG score, number of metastatic sites). Survival curves were analyzed using the Kaplan-Meier method. RESULTS: One hundred patients were included. According to the Pronopall score, patients were separated into group A (score 8-10, 7 patients), group B (score 4-7, 41 patients) and group C (score 0-3, 52 patients). Median overall survival was 73 days, CI [17-129], 228 days, CI [128-328] and 575 days, CI [432-718] for groups A, B and C, respectively. Survival at 2 months was 28 % for population A, 61 % for population B, and 94 % for population C. CONCLUSION: This study confirms that the Pronopall score still allows clinically relevant discrimination of patients, score C being associated with a good prognosis compared to scores A and B.

Baseline tumour size is an independent prognostic factor for overall survival in PD-L1 ≥ 50% non-small cell lung cancer patients treated with first-line pembrolizumab.

BACKGROUND: Advanced non-small cell lung cancer (NSCLC) with a PD-L1 tumour proportion score ≥ 50% can be treated with pembrolizumab alone. Our aim was to assess the impact of baseline tumour size (BTS) on overall survival (OS) in NSCLC patients treated with pembrolizumab versus chemotherapy. METHODS: This retrospective, multicentre study included all patients with untreated advanced NSCLC receiving either pembrolizumab (PD-L1 ≥ 50%) or platinum-based chemotherapy (any PD-L1). The primary endpoint was the impact of BTS (defined as the sum of the dimensions of baseline target lesions according to RECIST v1.1 criteria) on OS. RESULTS: Between 09-2016 and 06-2020, 188 patients were included, 96 in the pembrolizumab (P-group) and 92 in the chemotherapy group (CT-group). The median follow-up was 26.9 months (range 0.13-37.91) and 44.4 months (range 0.23-48.62), respectively, while the median BTS was similar, 85.5 mm (IQR 57.2-113.2) and 86.0 mm (IQR 53.0-108.5), respectively (p = 0.42). The median P-group OS was 18.2 months [95% CI 12.2-not reached (NR)] for BTS > 86 mm versus NR (95% CI 27.2-NR) for BTS ≤ 86 mm (p = 0.0026). A high BTS was associated with a shorter OS in univariate analyses (p = 0.009) as well as after adjustment on confounding factors (HR 2.16, [95% CI 1.01-4.65], p = 0.048). The CT-group OS was not statistically different between low and high BTS patients, in univariate and multivariate analyses (p = 0.411). CONCLUSIONS: After adjustment on major baseline clinical prognostic factors, BTS was an independent prognostic factor for OS in PD-L1 ≥ 50% advanced NSCLC patients treated first-line with pembrolizumab.

STK11/LKB1 Modulation of the Immune Response in Lung Cancer: From Biology to Therapeutic Impact.

The STK11/LKB1 gene codes for liver kinase B1 (STK11/LKB1), a highly conserved serine/threonine kinase involved in many energy-related cellular processes. The canonical tumor-suppressive role for STK11/LKB1 involves the activation of AMPK-related kinases, a master regulator of cell survival during stress conditions. In pre-clinical models, inactivation of STK11/LKB1 leads to the progression of lung cancer with the acquisition of metastatic properties. Moreover, preclinical and clinical data have shown that inactivation of STK11/LKB1 is associated with an inert tumor immune microenvironment, with a reduced density of infiltrating cytotoxic CD8+ T lymphocytes, a lower expression of PD-(L)1, and a neutrophil-enriched tumor microenvironment. In this review, we first describe the biological function of STK11/LKB1 and the role of its inactivation in cancer cells. We report descriptive epidemiology, co-occurring genomic alterations, and prognostic impact for lung cancer patients. Finally, we discuss recent data based on pre-clinical models and lung cancer cohorts analyzing the results of STK11/LKB1 alterations on the immune system and response or resistance to immune checkpoint inhibitors.

Dissociated Responses in Patients with Metastatic Solid Tumors Treated with Immunotherapy.

BACKGROUND: Immune checkpoint inhibitors have been demonstrated to improve overall survival. Atypical patterns of response have been reported, including dissociated response (DR). We evaluated the prevalence of DR. PATIENTS AND METHODS: Patients had to have a baseline computed tomography (CT) scan and at least one follow-up CT scan and two target lesions (TLs). Three types of DR were evaluated using RECIST1.1: DR1, defined as at least one progressive and one responding TL; DR2, defined as at least one progressive and one stable TL; and DR3, defined as at least one stable and one responding TL. RESULTS: A total of 1244 measurements of 272 TLs were performed in 100 patients. Forty-nine out of the 272 TLs (18%) had received old or recent radiotherapy, and 42 (15%) had been biopsied. An objective response was observed in 22 patients (22%) and on 52 TLs (19%). DR1 were observed in 8% of patients. At the tumor measurement level, the response rate was lower in the case of prior radiotherapy (29% vs 34%, p = 0.01) and higher in the case of prior biopsy (40% vs 32%, p = 0.02). CONCLUSIONS: A DR was observed in 8% of patients. Response rate was lower in the case of prior radiotherapy and higher in the case of prior biopsy.

Homozygous Co-Deletion of Type I Interferons and CDKN2A Genes in Thoracic Cancers: Potential Consequences for Therapy.

Homozygous deletion (HD) of the tumor suppressor gene CDKN2A is the most frequent genetic alteration in malignant pleural mesothelioma and is also frequent in non-small cell lung cancers. This HD is often accompanied by the HD of the type I interferons (IFN I) genes that are located closed to the CDKN2A gene on the p21.3 region of chromosome 9. IFN I genes encode sixteen cytokines (IFN-α, IFN-߅) that are implicated in cellular antiviral and antitumor defense and in the induction of the immune response. In this review, we discuss the potential influence of IFN I genes HD on thoracic cancers therapy and speak in favor of better taking these HD into account in patients monitoring.