J.-B. Guy

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.

Brain metastases from non-small cell lung carcinoma: Changing concepts for improving patients’ outcome

The management of Non Small Cell Lung Cancer (NSCLC) brain metastases is challenging, as this frequent complication negatively impacts patients quality of life, and can be a life-threatening event. Through a review of the literature, we discuss the main therapeutic options and the recent developments that improved (and complicated) the management of NSCLC brain metastases patients. Most current validated approaches are local with exclusive or combined surgery, whole brain radiotherapy (WBRT) and stereotactic radiotherapy (SRT). At the same time, there is a growing role for systemic treatments that might significantly postpone WBRT. Targeted therapies efficacy/toxicity profile remains to be defined but predictive and prognostic molecular factors integration could help to select treatments fully adapted to life expectancy and progression risk.

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.

Radiothérapie et biomarqueurs de la réparation de l’ADN

The identification of DNA repair biomarkers is of paramount importance. Indeed, it is the first step in the process of modulating radiosensitivity and radioresistance. Unlike tools of detection and measurement of DNA damage, DNA repair biomarkers highlight the variations of DNA damage responses, depending on the dose and the dose rate. The aim of the present review is to describe the main biomarkers of radiation-induced DNA repair. We will focus on double strand breaks (DSB), because of their major role in radiation-induced cell death. The most important DNA repair biomarkers are DNA damage signaling proteins, with ATM, DNA-PKcs, 53BP1 and γ-H2AX. They can be analyzed either using immunostaining, or using lived cell imaging. However, to date, these techniques are still time and money consuming. The development of omics technologies should lead the way to new (and usable in daily routine) DNA repair biomarkers.

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.

PURPOSEnAn 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.nnnMATERIALS AND METHODSnWe 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.nnnRESULTSnWe 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.nnnCONCLUSIONSnThe 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)

BACKGROUNDnSafety 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.nnnMETHODSnA 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.nnnRESULTSnOut 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 (nu202f=u202f74, 34.6%), analgesics (nu202f=u202f78, 36.4%), hypolipidemic drugs (nu202f=u202f57, 26.6%), proton pump inhibitors (nu202f=u202f46, 21.5%) and antiplatelet drugs (nu202f=u202f38, 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%).nnnCONCLUSIONnDrug-radiation interaction remains a subject of major interest, not only for conventional anticancer drugs, but also for NACTs. New trial designs are thus required.

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

PURPOSEnThe aim of the present study was to identify management strategies and outcomes of patients with stage IB1 cervical cancer with high recurrence risk.nnnMATERIALS AND METHODSnMedical 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.nnnRESULTSnForty-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).nnnCONCLUSIONnIn 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.

Comparaison dosimétrique d’une radiothérapie conformationnelle tridimensionnelle, d’une arcthérapie volumétrique modulée et d’une arcthérapie hybride pour la prise en charge du cancer bronchique

Objectif de l’etude L’objectif de cette etude etait de comparer les parametres dosimetriques de trois techniques de radiotherapie pour le traitement de cancers bronchiquesxa0: la radiotherapie conformationnelle tridimensionnelle, l’arctherapie volumetrique modulee (VMAT) et l’arctherapie hybride (Hybrid Arc). Materiel et methode Les donnees dosimetriques de 16xa0patients atteints d’un cancer bronchique de stade III, ayant ete pris en charge par l’arctherapie hybride ont ete replanifiees avec une technique radiotherapie conformationnelle tridimensionnelle, puis une VMAT sur le systeme de planification de traitement (Varian). Les trois techniques ont ete comparees sur la base d’histogrammes dose–volume pour la dose dans le volume cible previsionnelle, la dose dans les organes a risque et sur la base du nombre d’unites moniteurs par plan. Resultats L’arctherapie hybride avait significativement une meilleure homogeneite de dose, la moyenne des indices d’homogeneite (HIxa0=xa0[D 2xa0% xa0−xa0D 98xa0% ]/D 50xa0% ) (D x xa0% xa0: dose x xa0% du volume) etant de 8,19xa0pour l’arctherapie hybride, 10,15 ( p xa0=xa00,0004) pour la VMAT et 10,41 ( p xa0=xa00,0004) pour la radiotherapie conformationnelle tridimensionnelle. Les V 5 , V 10 xa0et V 20 (V x xa0: volume recevant x Gy) moyens au poumon sain (volume cible previsionnel poumons) etaient avec l’arctherapie hybride de 53,53xa0%, 35,97xa0% et 23,41xa0% respectivement et significativement plus faibles que ceux obtenus avec la VMAT et la radiotherapie conformationnelle tridimensionnelle. La dose moyenne dans poumon sain etait de 13,12xa0Gy avec l’arctherapie hybride, 13,36xa0Gy avec la VMAT (n.s) et 16,19xa0Gy avec la radiotherapie conformationnelle tridimensionnelle ( p xa0=xa00,0003). Le V 5 xa0moyen dans poumon controlateral etaient respectivement de 44,2xa0%, 49,66xa0% et 54,99xa0% avec l’arctherapie hybride, la VMAT et la radiotherapie conformationnelle tridimensionnelle et etaient significativement differents entre eux. Les nombres d’unites moniteur moyennes pour l’arctherapie hybride, la VMAT et la radiotherapie conformationnelle tridimensionnelle etaient respectivement de 451,94, 600,00xa0et 282,81xa0et significativement differentes entre eux. Conclusion Dans cette etude, l’arctherapie hybride, par comparaison a la VMAT et a la radiotherapie conformationnelle tridimensionnelle, permet une meilleure couverture du volume cible previsionnel, mais aussi une reduction des V 5 , V 10 xa0et V 20 xa0moyens du poumon sain, ce qui suggere une possible amelioration de l’indice therapeutique de la radiotherapie. Par consequent, l’arctherapie hybride semble une technologie adaptee au traitement des cancers bronchiques.

Impact du trajet entre le domicile et l’hôpital sur la fatigue des patients pris en charge par radiothérapie

Objectif de l’etude Les patients pris en charge par radiotherapie rapportent frequemment une fatigue genante, le plus souvent sans qu’une cause specifique ne puisse etre identifiee. Nous nous sommes interesses a l’impact des trajets quotidiens sur la fatigue des patients en cours de radiotherapie. Materiel et methode Cinq cent patients pris en charge en intention curative par radiotherapie pour un cancer du sein (350xa0patientes) ou un cancer de la prostate (150xa0patients) a l’institut de cancerologie Lucien-Neuwirth (Saint-Etienne, Loire), ont ete consecutivement inclus. Une echelle visuelle analogique (EVA) de fatigue (de 1 [absence de fatigue] a 10 [pire fatigue imaginable]) ainsi qu’un score de tolerance au traitement (de 1 [intolerance maximale au traitement] a 10 [meilleure tolerance imaginable]) ont ete recueillis aupres du patient, en fin de traitement. La distance et la duree du trajet entre le domicile et le centre ont ete colligees, ainsi que les donnees de toxicite aigue. La recherche de correlations a ete realisee au moyen du coefficient de Pearson. Resultats La distance moyenne d’un aller (du domicile a l’institut de cancerologie) etait de 22,96xa0km (±xa013,59) avec une distance maximale a 92xa0km. La duree moyenne du trajet etait de 27xa0min (±xa012) avec un trajet maximum de 1xa0h et 23xa0min. L’EVA moyenne de la fatigue etait de 4,01 (±xa02,57). Le score moyen de tolerance au traitement etait de 7,43 (±xa01,34). Aucune correlation significative n’a pu etre mis en evidence entre distance et EVA de fatigue (r2xa0=xa07·10–4), duree et lEVA de fatigue (r2xa0=xa09·10–6), distance et tolerance (r2xa0=xa04·10–4), duree et tolerance (r2xa0=xa019·10–4). La fatigue n’etait pas correlee avec la severite de la toxicite aigue radio-induite (r2xa0=xa013·103). Conclusion La distance entre le domicile et le centre de radiotherapie ne semble pas correlee avec la fatigue des patients en cours de traitement. Ces donnees questionnent sur la faisabilite de traiter les patients dans des centres referents de radiotherapie, meme situes loin de leur domicile.