N. Magné

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.

Altération de la réparation de l’ADN et cancer

Maintaining the genetic integrity is a key process in cell viability and is enabled by a wide network of repair pathways. When this system is defective, it generates genomic instability and results in an accumulation of chromosomal aberrations and mutations that may be responsible for various clinical phenotypes, including susceptibility to develop cancer. Indeed, these defects can promote not only the initiation of cancer, but also allow the tumor cells to rapidly acquire mutations during their evolution. Several genes are involved in these damage repair systems and particular polymorphisms are predictive of the onset of cancer, the best described of them being BRCA. In addition to its impact on carcinogenesis, the DNA damage repair system is now considered as a therapeutic target of choice for cancer treatment, as monotherapy or in combination with other cytotoxic therapies, such as chemotherapies or radiotherapy. PARP inhibitors are nowadays the best known, but other agents are emerging in the field of clinical research. The enthusiasm in this area is coupled with promising results and a successful collaboration between clinicians and biologists would allow to optimize treatment plans in order to take full advantage of the DNA repair system modulation.

Principe de prises en charge du carcinome à cellules de Merkel et place de la radiothérapie

Merkel cell carcinoma is a rare neuro-endocrine tumor of skin with a poor prognosis. Data available in literature are scarce. Current treatment for locoregional disease is based on combined treatment by surgery and radiotherapy. However these treatments are controversial. The aim of the present review is to sum up the different available studies and to compare national and international guidelines.

Conflict of interests for radiation oncologists: Harnessing disclosures from policy to reality.

PURPOSE An increasing attention is being paid to disclosures of conflicts of interests in the field of oncology. The purpose of this study was to examine how radiation oncologists report their conflicts of interests with pharmaceutical or technology industries. MATERIALS AND METHODS We collected the data of conflicts of interests disclosures in the abstract books from the annual 2012 and 2013 meetings of the American Society for Radiation Oncology (ASTRO) in Miami (FL, USA), and in Atlanta (GA, USA), respectively. Geographic origins of abstracts as well other factors were examined. RESULTS We identified a total of 4219 abstracts published in the past two years. The total number of involved authors was of 28,283. All of the published abstracts had conflicts of interests disclosures. Amongst them, 563 abstracts (13.4%) reported at least one potential conflict of interests, in which 1264 (4.5%) declared a potential conflict of interests in their disclosures. Geographic distribution of abstracts with financial relationship was as following: 67.9%, 15.5%, 7.7% and 7.7% for USA, Europe, Asia/Pacifica, and Canada, respectively. Abstracts with conflict of interest originated from North America in 75.6% of cases. USA distribution was 70.6% and 29.4% for Eastern and Western, respectively. CONCLUSIONS The proportion of physicians declaring financial conflicts of interests remains extremely low, whichever geographic area authors are from. In comparison to the rest of the world, the US proved itself better at declaring potential links. Changes in medical culture and education could represent a significant step to improve the process of revealing conflicts of interest in medical journal as well as in international meetings.

Harnessing drug/radiation interaction through daily routine practice: Leverage medical and methodological point of view (MORSE 02-17 study)

BACKGROUND Safety profile of the interaction between anticancer drugs and radiation is a recurrent question. However, there are little data regarding the non-anticancer treatment (NACT)/radiation combinations. The aim of the present study was to investigate concomitant NACTs in patients undergoing radiotherapy in a French comprehensive cancer center. METHODS A prospective cross-sectional study was conducted. All cancer patients undergoing a palliative or curative radiotherapy were consecutively screened for six weeks in 2016. Data on NACTs were collected. RESULTS Out of 214 included patients, a NACT was concomitantly prescribed to 155 patients (72%), with a median number of 5 NACTs per patient (range: 1-12). The most prescribed drugs were anti-hypertensive drugs (101 patients, 47.2%), psychotropic drugs (n = 74, 34.6%), analgesics (n = 78, 36.4%), hypolipidemic drugs (n = 57, 26.6%), proton pump inhibitors (n = 46, 21.5%) and antiplatelet drugs (n = 38, 17.8%). Although 833 different molecules were reported, only 20 possible modifiers of cancer biological pathways (prescribed to 74 patients (34.5%)) were identified. Eight out of the 833 molecules (0.9%), belonging to six drug families, have been investigated in 28 ongoing or published clinical trials in combo with radiotherapy. They were prescribed to 63 patients (29.4%). CONCLUSION Drug-radiation interaction remains a subject of major interest, not only for conventional anticancer drugs, but also for NACTs. New trial designs are thus required.

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. Its 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.

Outcomes and treatments of IB1 cervical cancers with high recurrence risk: A 13 years’ experience

PURPOSE The aim of the present study was to identify management strategies and outcomes of patients with stage IB1 cervical cancer with high recurrence risk. MATERIALS AND METHODS Medical files of all consecutive patients treated between 2004 and 2017 with external beam radiotherapy and/or brachytherapy for IB1 cervical cancer, whatever the lymph node status, were retrospectively reviewed. RESULTS Forty-two patients were included, with a median age of 49.8 years old. Median tumour size, estimated with the initial pelvic magnetic resonance imaging, was 26mm (interquartile range [IQR]=19.5-35). Histological types were mainly squamous cell carcinoma (59.5%) and adenocarcinoma (33.3%). Lymphovascular invasion was reported for 38.1% of patients. Pelvic lymph nodes were involved for eight patients (19.0%). Surgery was performed for 39 patients (92.9%). A neoadjuvant treatment was delivered for 20 patients (47.6%), an adjuvant treatment for 19 patients (45.2%) and an exclusive radiotherapy (with or without chemotherapy) followed by brachytherapy for three patients (7.1%). Pathologic complete response was achieved in 61.5% of patients. With a median follow-up of 5.8 years (IQR=2.6-9.4), five patients (11.9%) experienced a tumour relapse. The five-year disease-free survival was 79.5% (95% confident interval [CI]=66.9-94.4), the five-year overall survival was 87.8% (95% CI=77.2-99.8), and the five-year disease-specific survival was 94.2% (95% CI=86.7-100). CONCLUSION In current clinical practice, tailored treatments are delivered, and seems to give correct therapeutic index. However, clinical trials are needed to standardise treatment according to patient characteristics and recurrence risk factors.

Skin Cancers in Nonagenarian Patients: Special Focus on Radiotherapy

Sir d Cutaneous cancers are particularly frequent in the elderly and there are only scarce treatment data, especially for radiotherapy and nonagenarians [1,2]. We report the data of a study investigating this matter. We retrospectively investigated the feasibility of radiotherapy in patients over 90 years treated in five health care facilities. We analysed tumour characteristics, patient data, radiotherapy parameters, effectiveness and toxicity. Eighty-eight patients were included (mean age 93.2 years). Radiotherapy was intended curative in 63.6% of cases. Fifty-eight per cent of cases were squamous cell cancers, 29.5% basal cell cancers, 6.9% Merkel cell carcinomas, 4.5% melanomas and 1.1% adenocarcinoma. The median total dose was 40 Gy (10e60), the median number of fractions was seven (1e30) and the median dose per fraction was 6 Gy. The median follow-up from the date of completion of radiotherapy was 62 days (0e62 months). Tumour control was obtained in 58 patients (65.9% of cases), less than for younger patients [3]; however, 36 patients observed complete responses. For patients treated with palliative intent, symptoms improved for 19 patients (59.4%). Late toxicities were frequent, but mainly grade 1e2 (40%) and were mainly erythema, hyperkeratosis or lymphoedema. Two grade 3e4 toxicities were reported (8% of the cases). At last follow-up, 70 patients (79.5%) were alive; cancer was the main cause of death (50% of cases). This study shows that radiotherapy is a safe and effective non-surgical option in the treatment of skin cancers for the oldest population. Elderly patients should be treated