Radiothérapie post-opératoire pour les tumeurs épithéliales thymiques : données RYTHMIC

Thymic Epithelial Tumors (TETs) are rare intrathoracic malignancies for which surgery represents the mainstay of the treatment strategy. Postoperative radiotherapy (PORT) to the anterior mediastinal postoperative bed has been historically a standard of care. Through the prospective RYTHMIC cohort of patients, we previously assessed whether PORT decisions were in accordance with ESMO/RYTHMIC guidelines, and ultimately implemented in a cohort of 274 patients; we also verified how ITMIG definitions and recommendations for dose-volume constraints were actually followed in a real practice setting. METHODS Through a more prolonged follow-up, we further analysed the outcomes of those patients. RESULTS From a total of 274 patients enrolled in the cohort analysed for PORT decision-making, 187 were analysed with available data (84 lost of follow-up, 3 wit exclusion criteria). After a median follow-up of 5.1 years, 39 (21%) patients had presented TET recurrence: 27 (32%) in the PORT group, and 12 (12%) in the no-PORT group (p=0.001). Median recurrence-free survival (RFS) was 41.1 (95% CI: 29.2-53.0) months. The most frequent site of relapses among the PORT group was pleura (44%), versus the mediastinum in the no-PORT group (67%). RFS and OS were significantly superior in case of complete resection (p=0.04, and p=0,002). Only 12 patients had died. CONCLUSIONS Our data highlight the low - 21% - risk of TET recurrence after a follow-up of 5 years, and the excellent outcome of patients in terms of OS. A longer follow-up is needed in order to highlight differences in OS between groups. Our data show the limited value of stage and histology to predict recurrences, while completion of surgical resection remains the most significant prognostic and predictive factor for recurrences. Ultimately, we did not identify PORT as being significantly associated with RFS and OS. However, the lack of difference in RFS and OS between groups can be explain by a reduced risk of relapse in the PORT group. Further studies are needed to help identify subgroups of population who can beneficiate from PORT. The higher rate of extra-mediastinal relapses in the no-PORT group encourage us to implement a more frequent control of the disease after surgery.Introduction : Les tumeurs épithéliales thymiques sont des tumeurs rares intrathoraciques pour lesquelles le traitement principal est la chirurgie. La radiothérapie post-opératoire (PORT) fait partie du traitement en cas de tumeurs agressives ou de résection incomplète. La base de données RYTHMIC recense les patients atteints de tumeurs thymiques sur le territoire national français. En s’appuyant sur ces données, nous avons précédemment étudié, sur 274 patients, si la décision de réaliser une PORT était concordante avec les recommandations de l’ESMO/RYTHMIC et si les modalités de la PORT suivaient les recommandations internationales. Méthodes. Grâce à un suivi de 5 ans de cette même cohorte, nous analysons ici la survie sans récidive (RFS) ainsi que la survie globale (OS) de patients opérés d’un thymome. Résultats. Sur les 274 patients analysés, 84 patients ont été perdus de vue et 3 exclus de l’analyse. Après un suivi médian de 5,1 années, 39 (21%) ont récidivé. La survie sans récidive est de 41,1mois (95% CI : 29,2-53,0). Concernant la majorité des récidives, elles étaient localisées dans la plèvre pour le groupe PORT (n=12 soit 44%), versus dans le médiastin pour le groupe non-PORT (n=8 soit 67%) laissant penser que la PORT puisse réduire les récidives médiastinales. La RFS ainsi que l’OS étaient significativement inférieure en cas de résection incomplète (p=0,04 et p=0,002). Nous avons observé 12 décès. Conclusion. Ce travail montre un risque de rechute à 5 ans de 21%. Le stade et l’histologie initiaux prédisent mal la récidive. En revanche la chirurgie incomplète reste le facteur pronostic et prédictif majeur de rechute

Management of cutaneous toxicities under amivantamab (anti MET and anti EGFR bispecific antibody) in patients with metastatic non-small cell lung cancer harboring EGFR Exon20ins: towards a proactive, multidisciplinary approach

International audienceContexte. The Epidermal Growth Factor Receptor (EGFR) is mutated in 10–15% of patients with lung adenocarcinoma. At metastatic stage EGFR tyrosine kinase inhibitors (TKIs) are used front line for patients harboring targetable mutations. Novel anti-EGFR therapies are being developed. Amivantamab is a bispecific anti-EGFR and anti-MET antibody with expected skin toxicities. Objective: We developed here guidelines for prevention and treatment of cutaneous toxicities under amivantamab according to our experience at Institut Curie. Materiel & Method: The first patients with metastatic lung cancer harboring EGFR Exon20ins mutation, included in the phase 1 CHRYSALIS trial and cured at Institute Curie from November 1st 2019 until December 31st 2021 were selected for this work. Retrospectively, all cutaneous adverse events were registered and classified according to the CTCAE 6.0 classification, and actions we implemented to minimize and treat these adverse events were collected. We then developed guidelines based on these datas. Results: A total of seven patients started amivantamab as monotherapy. The two most frequent dermatological adverse events were: acneiform rash and paronychia (100 % of patients). Other adverse events presented by the patients were reported: modification of hair growth with hypertrichosis in 50 % of men (n = 1/2) and hirsutism in 80 % of women (n = 4/5); skin abrasion of the scalp in 71 % (n = 5/7); and skin fissure in 57 % (n = 4/7). We recommend first a rigorous inspection of the skin and teguments to determine the risk rate to have dryer skin under treatment; second a prevention of paronychia/acneiform rash/and skin fissures with prophylactic tetracycline, skin moisturizing, and hygienic measures starting at least 14 days before treatment initiation; third a particular attention to the psychological impact of skin toxicities with access to psychological support. Conclusion: We propose here guidelines for the management of dermatological toxicities under amivantamab with a multidisciplinary approach for the proactive management of cutaneous toxicities with a focus on preventive actions

Impact of COVID-19 on the management of patients with thoracic cancers in a tertiary referral center

International audienceIntroduction: Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 has spread worldwide in 2020 leading the World Health Organization to declare a pandemic. Patients with thoracic cancers have been reported at higher risk to develop severe disease, and die from COVID-19. In this setting, clinical practice recommendations for the management of patients were published. We report here how these guidelines were implemented in a routine practice setting. Methods: We retrospectively collected the characteristics, treatment regimen and modification, as well as COVID-19 status and death for all patients with thoracic malignancies scheduled for an appointment at Institute Curie from March 23rd to April 17th 2020. Results: A total of 339 patients were included. Treatment strategy was modified for a total of 110 (32 %) patients because of COVID-19; these modifications were in accordance with guidelines for 92 % of patients. The majority of dose modifications were related to immune checkpoint inhibitors, for which switch to flat dosing every 4–6 weeks was made. A total of 5 (1.5 %) patients were diagnosed with COVID-19 disease, 1 of whom died from disease complication. Conclusion: Our study provides a unique insight in the decision making for patients with thoracic malignancies in the setting of COVID-19 outbreak, showing how guidelines were implemented in the clinic, and what may be optimized in the clinical practice of thoracic oncology in the future

Immunothérapie des cancers bronchiques non à petites cellules métastatiques, de la première ligne à la résistance et sa prise en charge

International audienceL’immunothérapie seule ou en association avec la chimiothérapie fait désormais partie intégrante du traitement du CPNPC métastatique. Ce traitement transforme la prise en charge de ces cancers, avec 20 à 30% des patients atteignant une longue survie. Cependant, la progression de la maladie sous traitement est toujours la règle pour la majorité des patients, ce qui soulève des problèmes à la fois dans la compréhension de ses mécanismes et dans la prise en charge appropriée ultérieure. Cette étude examine les options thérapeutiques actuelles et propose des solutions pour contourner la résistance à l’immunothérapie. Les mécanismes de résistance à ces traitements sont également analysés

Brief Report on Teleconsultation in Lung Cancer: Toward a Semiotic Paradigm Shift?

International audienceIntroduction: Telehealth is taking an increasingly important part of medicine. This practice change is being accelerated by the pandemic linked to coronavirus disease 2019. Oncology is a medical specialty for which this paradigm shift is particularly relevant.Methods: We developed a survey aiming at evaluating the use of teleconsultation by physicians managing patients with lung cancer in France. The survey was available online from December 15, 2020, to February 10, 2021.Results: Answers were obtained from 142 clinicians (73.9% pneumologists, 18.3% medical oncologists, and 7.7% with another specialty), 129 (90.8%) of whom had already performed teleconsultation. Among those, 123 (95.3%) started after the coronavirus disease 2019 pandemic. In addition, 72.9% had a moderate usage of this tool (<10 teleconsultations/mo). The frequency of clinicians never using teleconsultation was higher in private practices (p = 0.029). The two clinical situations for which teleconsultation was frequently used were visits during treatment without imaging assessment (53.5%) and post-treatment surveillance (80.3%). Depending on the type of treatment received, the frequency of teleconsultation was variable. Lung cancer subtype also affected the clinician's practice. Indeed, 47.2% never proposed this tool for SCLC. Teleconsultation was considered to be of no contribution, a moderate contribution, a significant contribution, or a revolution of the clinical practice for 14.1%, 66.2%, 10.6%, and 2.1% of the respondents, respectively. The participants expected to decrease, stabilize, or increase their teleconsultation activity in 18.3%, 52.8%, and 23.2% of the cases, respectively.Conclusions: Most thoracic oncologists in France are using teleconsultation, mostly as an additional tool that should not replace the doctor-patient in-person relationship

Comprehensive Genomic Profiling of 274 Thymic Epithelial Tumors Unveils Oncogenic Pathways and Predictive Biomarkers

International audienceBACKGROUND: Thymic malignancies represent a heterogeneous group of rare thoracic cancers, which are classified according to the World Health Organization histopathologic classification, that distinguishes thymomas from thymic carcinomas. Data regarding the biology of those tumors are limited in the literature, and the vast majority have been obtained using surgical specimens from early-stage disease. Meanwhile, treatment of advanced, refractory thymic tumors currently relies on chemotherapy, with limited efficacy. Comprehensive genomic profiling (CGP) of advanced, refractory tumors would open some opportunities for innovative treatments. PATIENTS AND METHODS: A total of 90 and 174 consecutive patients with thymoma or thymic carcinoma, respectively, for whom formalin-fixed, paraffin-embedded specimens from recurrent, refractory tumor were sequenced, were included. Sequencing was performed using hybridization-captured, adaptor ligation-based libraries to a mean coverage depth of >500× for up to 315 cancer-related genes plus 37 introns from 28 genes frequently rearranged in cancer. RESULTS: Thymomas featured a low frequency of genomic alterations (average of 1.8/tumor), and low levels of TMB. The genomic alterations identified in more than 10% of cases were in the CDKN2A/B and TP53 genes. Amplification in the NTRK1 gene was found in an unresectable, stage III, type B3 thymoma. Thymic carcinomas featured a significantly higher frequency of alterations at 4.0/tumor (P < .0001). Clinically relevant genomic alterations were observed in the CDKN2A, KIT, and PTEN/PI3K/MTOR pathways. Elevated TMB in thymic carcinomas was uncommon with only 6% of cases featuring ≥10 mutations/Mb. CONCLUSIONS: Our cohort is the largest available so far, reporting on CGP of thymic epithelial tumors in the setting of advanced disease. The identification of clinically relevant genomic alterations in the KIT, PI3K, CDKN2A/B, or NTRK genes provides a strong rationale for potential precision medicine approaches using targeted agents. A subset of thymic carcinomas show high tumor mutation burden, what may be a predictor of efficacy of immune checkpoint inhibitors

Gain of Aggressive Histological and Molecular Patterns after Acquired Resistance to Novel Anti-EGFR Therapies in Non-Small Cell Lung Cancer

International audienceNovel anti-EGFR therapies target resistance to standard-of-care anti-EGFR in patients with metastatic lung cancer. We describe tumors at progression versus at the initiation of novel anti-EGFR agents in patients with metastatic lung adenocarcinoma harboring EGFR mutation. This clinical case series reports the histological and genomic features and their evolution following disease progression under amivantamab or patritumab-deruxtecan in clinical trials. All patients had a biopsy at disease progression. Four patients harboring EGFR gene mutations were included. Three of them received anterior anti-EGFR treatment. Median delay to disease progression was 15 months (range: 4–24). At progression, all tumors presented a mutation in the TP53 signaling pathway associated with a loss of heterozygosis (LOH) of the allele in 75% (n = 3), and two tumors (50%) presented an RB1 mutation associated with LOH. Ki67 expression increased above 50% (range 50–90%) in all samples compared to baseline (range 10–30%), and one tumor expressed a positive neuroendocrine marker at progression. Our work reports the potential molecular mechanisms of resistance under novel anti-EGFR in patients with metastatic EGFR-mutated lung adenocarcinoma, with the transformation to a more aggressive histology with acquired TP53 mutation and/or the increase in Ki67 expression. These characteristics are usually found in aggressive Small Cell Lung Cancer

Surgical or medical strategy for locally-advanced, stage IIIA/B-N2 non-small cell lung cancer: Reproducibility of decision-making at a multidisciplinary tumor board

International audienceBackground: Stage IIIA/B-N2 is a very heterogeneous group of patients and accounts for one third of NSCLC at diagnosis. The best treatment strategy is established at a Multidisciplinary Tumor Board (MTB): surgical resection with neoadjuvant or adjuvant therapy versus definitive chemoradiation with immune checkpoint inhibitors consolidation. Despite the crucial role of MTBs in this complex setting, limited data is available regarding its performances and the reproducibility of the decision-making. Methods: Using a large cohort of IIIA/B-N2 NSCLC patients, we described patient's characteristics and treatment strategies established at the initial MTB: with a “surgical strategy” group, for potentially resectable disease, and a “medical strategy” group for non-resectable patients. A third group consisted of patients who were not eligible for surgery after neoadjuvant treatment and switched from the surgical to the medical strategy. We randomly selected 30 cases (10 in each of the 3 groups) for a blinded re-discussion at a fictive MTB and analyzed the reproducibility and factors associated with treatment decision. Results: Ninety-seven IIIA/B-N2 NSCLC patients were enrolled between June 2017 and December 2019. The initial MTB opted for a medical or a surgical strategy in 44% and 56% of patients respectively. We identified histology, tumor size and localization, extent of lymph node involvement and the presence of bulky mediastinal nodes as key decision-making factors. Thirteen patients were not eligible for surgical resection after neoadjuvant therapy and switched for a medical strategy. Overall concordance between the initial decision and the re-discussion was 70%. The kappa correlation coefficient was 0.43. Concordance was higher for patients with limited mediastinal node invasion. Survival did not appear to be impacted by conflicting decisions. Conclusions: Reproducibility of treatment decision-making for stage IIIA/B-N2 NSCLC patients at a MTB is moderate but does not impact survival

Accelerated subsequent lung cancer after post-operative radiotherapy for breast cancer

International audienceBackground: Post-operative whole breast radiotherapy for breast cancer (BC) may increase the risk of subsequent lung cancer (LC). The impact of radiotherapy intensification (boost) has not been specifically explored in this context. We investigated the role of radiation modalities on the development of subsequent LC among our patients treated by radiotherapy for localized BC. Methods: All patients with a diagnosis of LC between 2000 and 2020 with a history of prior localized BC treated by surgery and post-operative radiotherapy were retrospectively reviewed. Primary endpoint was time to first diagnosis of LC after BC treatment with radiotherapy (RT). Results: From 98 patients who developed subsequent LC after primary BC treated with post-operative RT, 38% of patients (n = 37) received an additional RT boost, and 46% (n = 45) received hormonal treatment post radiation. A total of 61% (n = 60) were smokers. With regards to LC characteristics, adenocarcinoma was the most frequent histology (68%, n = 66); 36% (n = 35) harbored at least 1 molecular alteration, 57% (n = 20) of them being amenable to targeted therapy. Median time to first diagnosis of LC was 6 years [1.7–28.4 yrs] in the whole cohort. In the subgroup of patients treated with boost this time was reduced to 4 years [1.8–20.8 years] compared to 8 years for patients without boost [1.7–28.4 yrs] (p = 0.007). Boost, smoking usage, endocrine therapy, and age <50 yrs old at BC radiation remained independent factors associated with shorter time to first diagnosis of LC after BC treatment. Discussion: We report for the first time the potential impact of boost -part of BC radiation treatment- for BC on the risk of subsequent LC. The impact of low dose radiation on lung parenchyma could explain this phenomenon, but the underlying physiopathology is still under investigation. This work highlights the need for clinicians to identify patients at risk of developing faster subsequent thoracic malignancy after BC radiation, for implementing personalized surveillance