Predictive resistance factors in lung cancer patients treated with Nivolumab. Retrospective study.

OBJECTIVES: Immunotherapy is the current treatment in non-small cell lung cancer (NSCLC). 20% of patients treated with immunotherapy have a prolonged response. What about the remaining 80%? How can we explain that some patients get no benefit from immunotherapy? MATERIEL AND METHODS: We retrospectively analyzed predictive factors of primary or secondary resistance to immunotherapy in NSCLC patients from 2 French hospitals between 2015 and 2018. Moreover, we evaluated whether PD1 inhibitor had an impact on the antitumor effects of salvage chemotherapy administered after immunotherapy. We chose to focus on taxanes. RESULTS: Ninety-six patients were included in this cohort, 65(68%) patients were considered as having primary resistance and 31(32%) secondary resistance. Resistant populations did not differ. At immunotherapy initiation, median survival was 4.6 months for primary resistant patients (95%CI-4.6-6.8) and 15.6 months (95%CI-9.8-NA) for secondary resistant patients. The disease control rates with taxane were 15% in pre immunotherapy conditions vs 50% in post immunotherapy. Response rates improved regardless of the status of resistance. CONCLUSION: This study enriches data about immunotherapy in real-life in NSCLC. Prognostic resistance factors still seem complicated to identify. The high rate of taxane responders in post immunotherapy in this retrospective cohort support the use of taxane in therapeutic escape.

Acquired ATRX Loss and ALT Phenotype Through Tumor Recurrences in a Case of Pleomorphic Xanthoastrocytoma Suggest Their Possible Roles in Tumor Progression.

Pleomorphic xanthoastrocytoma (PXA) is classified as an astrocytic glioma occurring most often in children or young adults. Molecular alterations in PXA are not fully known, especially those associated with tumor progression. We describe a patient with several relapses of a PXA. The tumor showed an acquired ATRX loss through tumor evolution. We tested alternative lengthening of telomeres (ALT) with the C-circle test. While the test was negative in the first tumor, a high circle activity was detected in the last relapse, suggesting an acquired ALT phenotype. Our data not only confirm previous findings of the possible occurrence of ATRX mutations in PXA but also suggest that this alteration is linked to PXA progression. In small biopsies, tumors with ATRX loss, without IDH or histone mutation, pathologists should consider the diagnosis of PXA, especially if associated with BRAF V600E mutation, CDKN2A deletion, and ALT.

Current management of stage I testicular germ cell tumors in a French cancer institute. A practice analysis over the 10 past years.

BACKGROUND: Testicular Germ Cell Tumors (TGCTs) represent the most frequent malignant tumour among young male adults. Orchiectomy alone cure 80% of stage I. Standard options after orchiectomy include radiotherapy (RT), chemotherapy (CT) by 1 cycle of carboplatin AUC 7 or active surveillance (SV) for seminomatous GCTs (SGCT) and retroperitoneal lymphadenectomy (RPLND), CT by 1 or 2 cycles of Bleomycine Etoposide Cisplatine (BEP) or active surveillance for nonseminomatous GCTs (NSGCT). Adjuvant treatments decrease the relapse rate after orchiectomy with substantial toxicities without any benefit on overall survival. Recent guidelines accorded utmost importance on SV rather than adjuvants strategies. The main objective of this study was to describe our current practice over the 10 past years in regard of these recommendations. METHODS: Data of 50 patients with stage I GCT treated in our institute were collected between 2006 and 2016. Demographic and anatomopathologic data were reported. Clinical practice in our center was analyzed during two periods [2006-2011] and [2012-2016] according to the European Association of Urology Guidelines in 2011. RESULTS: Patient's median age was 35.3 years. The analysis of clinical practice during the last 10 years showed that in SGCT, main treatment was RT than SV and CT. This option declined over the years (89% between 2006-2010 versus 53% between 2011-2016) whereas SV was more often employed (27% between 2011-2016 versus none between 2006-2010). Surveillance was used for 64% of NSGCT. CONCLUSIONS: In our center, RT was less used over the years for the benefit of SV which is recommended by guidelines.

Maintenance Therapy in Metastatic Solid Tumors: Innovative Strategy or Simple Second-line Treatment?

Managing metastatic diseases involves defining the best strategy that is supposed to take into account both efficacy and quality of life. To this end, clinicians use stop and go or maintenance strategies. As a matter of fact, 2 maintenance strategies can be distinguished: continuation maintenance using a drug already present in induction treatment and switch maintenance with a newly introduced drug. Several drugs have been approved as maintenance therapy with several current indications in solid tumors. Questions remain concerning such strategies, notably duration, cost, tolerability, and shortcut between switch maintenance and early second line. If the concept of maintenance strategy remains trendy with numerous trials ongoing, several issues are still pending. The aims of this review were to accurately define and describe the various facets of maintenance therapy through its several indications in real life and then to discuss the future challenges of maintenance therapy in oncology.

[HPV: Carcinogenic implications and preventive measures]. / Le papillomavirus : implications carcinologiques et mesures préventives.

Human oncogenic papillomaviruses (HPV) have an increasingly prominent role in the genesis of many cancers. The oncogenic mechanisms associated with HPV are now better known and make it possible to explain the etiopathogenesis of the association. HPV status is now sought for certain cancers and conditions both prognosis and management of patients. Preventive antiviral vaccination has become a real public health issue and aims to effectively reduce the prevalence of cervical, anal and oropharynx cancer, HPV-associated. However, vaccination against HPV still lags behind. The purpose of this review is to redefine the involvement of HPV in several cancers as well as current therapeutic challenges of HPV-related cancers, notably in term of prevention.

Radiotherapy in triple-negative breast cancer: Current situation and upcoming strategies.

Triple-negative breast cancer (TNBC) (estrogen receptor-negative, progesterone receptor-negative, and HER2-negative) is viewed as an aggressive subgroup of breast cancer. Treating patients with TNBC remains clinically challenging. It's now well established than radiation therapy is able to improve locoregional control in breast cancer patients both after breast conserving surgery or mastectomy, with positive impact in high-risk patients for long-term survival. Biologic characterization of breast tumor different subtypes, in particular the heterogeneous subtype of TNBC could permit to adapt the treatment plan. In the present review, summarizing the molecular types, we describe clinical features and postoperative radiotherapy current situation for TNBC, and we provide new strategies and directions through an adapted radiation therapy.

[Immunotherapy: Activation of a system not a pathway]. / Immunothérapie : après le focus sur les voies de signalisation, l'activation d'un système.

Immunotherapy is on the roll. After revolutionary effects in melanoma, immunotherapy is invading other locations. If current treatments, chemotherapies or targeted therapies block one pathway, immunotherapy should be understood as the activation of a whole system. Indeed, oncogenesis process is defined as an escape of the immune system and the stimulation of this system can block the carcinogenic process. The aim of the present review is to describe the place of immunotherapy in the treatment of solid cancers.