Benoîte Méry

Targeting head and neck tumoral stem cells: From biological aspects to therapeutic perspectives.

Head and neck squamous cell cancer (HNSCC) is the sixth most common cancer in the world. Effective therapeutic modalities such as surgery, radiation, chemotherapy and combinations of each are used in the management of the disease. In most cases, treatment fails to obtain total cancer cure. In recent years, it appears that one of the key determinants of treatment failure may be the presence of cancer stem cells (CSCs) that escape currently available therapies. CSCs form a small portion of the total tumor burden but may play a disproportionately important role in determining outcomes. CSCs have stem features such as self-renewal, high migration capacity, drug resistance, high proliferation abilities. A large body of evidence points to the fact that CSCs are particularly resistant to radiotherapy and chemotherapy. In HNSCC, CSCs have been increasingly shown to have an integral role in tumor initiation, disease progression, metastasis and treatment resistance. In the light of such observations, the present review summarizes biological characteristics of CSCs in HNSCC, outlines targeted strategies for the successful eradication of CSCs in HNSCC including targeting the self-renewal controlling pathways, blocking epithelial mesenchymal transition, niche targeting, immunotherapy approaches and highlights the need to better understand CSCs biology for new treatments modalities.

The evolving locally-advanced non-small cell lung cancer landscape: Building on past evidence and experience

Lung cancer is a major public health concern worldwide. Progress in improving 5-year survival is lagging behind comparable survival rates in other common cancers. The majority of patients with locally advanced non-small cell lung cancer (NSCLC) are not suitable for surgical resection, hence the major role of radical radiotherapy. Advances in radiotherapy techniques allow targeted treatment of the disease, whilst minimizing the dose to organs at risk. Recent research into fractionation schedules, with hyperfractionated and accelerated radiotherapy regimens has been promising. Platinum-based chemotherapy has long been the standard of care for the initial treatment of advanced NSCLC. However, if radical radiotherapy remains the cornerstone of treatment for patients with unresectable advanced NSCLC either as single modality treatment or with concomitant chemotherapy, advances in understanding of tumor molecular biology and targeted drug development should bring targeted agents into the NSCLC management. The development of numerous therapeutic approaches has made the locally advanced NSCLC world change. An up-to-date overview of the current literature on updated chemotherapeutic agents, targeted therapy, immunotherapy, radiotherapy in stage III NSCLC is provided.

In Vitro Cell Death Determination for Drug Discovery: A Landscape Review of Real Issues

Cell death plays a crucial role for a myriad of physiological processes, and several human diseases such as cancer are characterized by its deregulation. There are many methods available for both quantifying and qualifying the accurate process of cell death which occurs. Choosing the right assay tool is essential to generate meaningful data, provide sufficient information for clinical applications, and understand cell death processes. In vitro cell death assays are important steps in the search for new therapies against cancer as the ultimate goal remains the elaboration of drugs that interfere with specific cell death mechanisms. However, choosing a cell viability or cytotoxicity assay among the many available options is a daunting task. Indeed, cell death can be approached by several viewpoints and require a more holistic approach. This review provides an overview of cell death assays usually used in vitro for assessing cell death so as to elaborate new potential chemotherapeutics and discusses considerations for using each assay.

Preclinical models in HNSCC: A comprehensive review.

Head and neck cancer remains a significant public health concern. About 60% of patients die within 5years due to local recurrence. Head and neck squamous cell carcinoma (HNSCC) cell lines are important preclinical models in the search for new therapies against this disease. Furthermore, there is a need to test novel drugs before introduction into clinical practice. A preclinical model that closely resembles the in vivo situation would be highly valuable. In the last few decades, a multicellular spheroid model has gained attention as its behavior was comparable to in vivo tumors. Basic research is necessary to achieve an understanding of the normal and pathological state but cannot, in itself, provide sufficient information for clinical applications. Indeed, animal models are an inevitable prelude to assess the efficacy of new therapeutic approaches in HNSCC. The present review proposes an overview of HNSCC pre-clinical models in order to further understand the oncogenic properties for HNSCC and translate these findings into clinic for patients.

Mélanomes du tractus génital féminin : état des lieux

Melanoma of the female genital tract is a rare location (less than 2% of melanomas all sites combined). These cancers have a very poor prognosis, due to the delay in diagnosis. Vulvar location is about 1% of melanomas then the vaginal location, uterine and ovarian. There is no consensus to date regarding their care, due to the rarity of the lesions. Their treatment must however be based on the current data concerning gynaecological cancers as well as standard management of cutaneous melanoma. The treatment is often based on conservative surgery, because radical resection does not improve survival. For the vulva and vagina, reconstructive surgery is possible. Treatment is sometimes supplemented by chemotherapy or radiotherapy, which could improve local control. The interest in the use of targeted therapy in these locations is not well known because of their rarity, but the study of genes c-Kit and BRAF provides new prospects for treatment. The objective of this review is to describe and report the current state of knowledge about gynaecologic melanomas.

Atrial fibrillation in cancer patients: Hindsight, insight and foresight

An increase of atrial fibrillation (AF) incidence in cancer patients has recently been pointed out, with complex interrelationships between these two entities on top of surgery factors. Most of present knowledge comes from retrospective studies or data from registries but the underlying mechanisms of the association between atrial fibrillation and cancer are still unclear. An increased risk of AF in cancer patients could represent a major public health problem although scarce information is available for the challenging management of such patients with distinctive features, especially in terms of antithrombotic therapy. Elaborate evidence-based approaches are thus required. This review provides an insight into AF among cancer patients through an overview of the underlying mechanisms, epidemiology evidence and future therapeutic challenges.

Real-World Outcomes of Combination Chemotherapy with Trabectedin plus Pegylated Liposomal Doxorubicin in Patients with Recurrent Ovarian Cancer: A Single-Center Experience.

Background: Trabectedin plus pegylated liposomal doxorubicin (PLD) proved efficacious as second-line treatment for patients with recurrent ovarian cancer (ROC). Methods: We report a single-center retrospective analysis of the efficacy and tolerance of trabectedin 1.1 mg/m2 every 3 weeks in a cohort of real-life ROC patients. Results: From February 2012 to January 2014, 17 patients were treated with trabectedin alone or combined with PLD. Median age was 61 years (range: 48-78). Performance status was 0-1 in 16 patients (94%). Disease response rate was 53% and disease control rate was 76%. At the end of the follow-up, 8 patients (47%) were alive. Median overall survival was 17.6 months (95% CI 13.6 to not reached). Median progression-free survival was 6.7 months (95% CI 5.4-10.0). The most frequent grade 3-4 toxicities were neutropenia (n = 4, 24%) and nausea/vomiting (n = 4, 24%). Conclusion: Trabectedin combined with PLD seems efficient in and well tolerated by real-life ROC patients.

Chemotherapy Regimen in Nonagenarian Cancer Patients: A Bi-Institutional Experience

Background: The elderly population in Western countries is growing and constitutes a public health issue. Concomitantly, age-related diseases such as cancer increase. There are few data on the efficacy, tolerability and toxicity of specific anticancer therapy in the very elderly patients; therefore, their management is not standardized. Methods: In this bi-institutional study, we reviewed medical records of patients who received or continued specific anticancer therapy beyond the age of 90 years. Geriatric assessment was not reported for our patients. Twelve patients were enrolled. Their general health condition was good, and half of them were living in elderly institutions. Ten patients had a solid tumor and 2 were treated for hematological malignancies. Most were diagnosed with a locally advanced or metastatic disease, and the goal of treatment was curative for only 1 patient. Six patients received chemotherapy as first-line treatment, 4 patients received targeted therapy and 2 received concomitant chemoradiation. Four patients received a second-line treatment. Results: Despite a significant reduction in treatment posology in half of the patients, 8 acute grade 3/4 toxicities were reported and 2 patients died of treatment-related septic shock. Median duration of first-line treatment was 3.2 months, and progression-free survival ranged from 18 to 311 days. Overall survival ranged from 18 days to 11 years. Conclusion: Aging is a heterogeneous process, and management of elderly patients is a multidisciplinary approach. Geriatric assessment helps to identify older patients with a higher risk of morbidity/mortality and allows to assess the risks and benefits of specific anticancer therapy. The choice of treatment should be based primarily on the expected symptomatic benefit, and treatment should not compromise the quality of life.

Radiosensibilité et/ou résistance des cancers ORL : aspects biologiques

Radiation therapy is a cornerstone of head and neck cancer management. Technological improvements in recent years in radiation therapy, with intensity-modulated techniques, reinforce even more its role. However, both local and locoregional relapses are still observed. Understanding biological mechanisms of treatment resistance is a topic of major interest. From the cancer cell itself, its ability to repair and proliferate, its microenvironment and oxygenation conditions, migratory and invasive capacity, to biological parameters related to the patient, there are many mechanisms involving radiosensitivity and/or radioresistance of head and neck cancer. The present study explores the main biological mechanisms involved in radiation resistance of head and neck cancer, and describes promising therapeutic approaches.

Real-World Vinflunine Outcomes in Bladder Cancer in a Single-Institution Study: Moving Beyond Clinical Trials

PURPOSE Intravenous vinflunine 320 mg/m(2) every 3 weeks plus best supportive care resulted in better overall survival in comparison with best supportive care alone for eligible patients with failure of prior therapy with locally advanced or metastatic transitional cell cancer of urothelial tract (TCCU). The objective of the present study was to describe our real-life experience of vinflunine for treatment of patients with TCCU. PATIENTS AND METHODS We retrospectively investigated all patients with TCCU who received at least 1 cycle of vinflunine. RESULTS Nineteen patients were treated between May 2010 and March 2014 in a compassionate-use program. Performance status was poor in our real-life cohort, with 6 patients (32%) with an Eastern Cooperative Oncology Group performance status of 2. Median duration of vinflunine treatment was 2.4 months (range, 0-4.3 months), and median number of cycles was 3 (range, 1-6). Total response rate was 32%, with partial responses only. Disease control rate was 53%, with a median duration of 7.7 months (range, 6.0-9.4 months). Median progression-free survival was 87 days, or 2.9 months (range, 0.7-11.7 months). After vinflunine treatment, 42% of patients received from 1 to 3 additional lines of chemotherapy. The most frequent grade 4 toxicities were constipation (26%), with 3 intestinal obstructions (16%) and 1 mechanical ileus (5%); and asthenia and fatigue (21%). CONCLUSION Vinflunine, as a TCCU second-line chemotherapy, brings benefits, particularly in cases where there is no alternative treatment.