Alain Toledano

Phase III Trial of Concurrent or Sequential Adjuvant Chemoradiotherapy After Conservative Surgery for Early-Stage Breast Cancer: Final Results of the ARCOSEIN Trial

PURPOSE In 1996, we initiated the French multicenter phase III randomized trial to compare the effect on disease-free survival (DFS) of concurrent versus sequential chemotherapy (CT) and radiotherapy (RT) after breast-conserving surgery for stages I and II breast cancer. This report presents the clinical results with a median follow-up of 60 months. PATIENTS AND METHODS Between February 1996 and April 2000, 716 patients were entered onto this trial. Adjuvant treatment began within 6 weeks after surgery. Sequential treatment of CT administered first followed by RT was compared with concurrent treatment of CT administered with RT. The CT regimen consisted of mitoxantrone (12 mg/m2), fluorouracil (500 mg/m2), and cyclophosphamide (500 mg/m2) on day 1, and it was repeated every 21 days for six courses. RT was delivered to the breast and, when indicated, to the regional lymphatics. RESULTS There was no statistically significant difference in treatment in the 5-year DFS (80% in both groups; P = .83), locoregional recurrence-free survival (LRFS; 92% in sequential v 95% in concurrent; P = .76), metastasis-free survival (87% in sequential v 84% in concurrent; P = .55), or overall survival (90% in sequential v 91% in concurrent; P = .76). Nevertheless, in the node-positive subgroup, the 5-year LRFS was statistically better in the concurrent arm (97% in concurrent v 91% in sequential; P = .02), corresponding to a risk of locoregional recurrence decreased by 39% (hazard ratio, 0.61; 95% CI, 0.38 to 0.93). CONCLUSION This treatment protocol remains an appealing clinical option for many women with operable breast cancer at a high risk of recurrence. Combination treatments with new drugs for breast cancer are warranted.

Depression is associated with some patient-perceived cosmetic changes, but not with radiotherapy-induced late toxicity, in long-term breast cancer survivors.

Although depression is prevalent in long‐term breast cancer survivors (LTBCS; ≥5 years since diagnosis), it is underdiagnosed and undertreated. A better understanding of factors associated with depression could improve depression screening, treatment, and prevention in this population. Our study aimed to assess the link between patient and doctor ratings of breast cosmetic outcomes, late radiotherapy toxicity, and depression in LTBCS.

Impact des complications tardives de la radiothérapie, de la dépression et de l’anxiété sur la qualité de vie à long terme dans le cancer du sein

INTRODUCTION This study aimed to assess the impact of late treatment toxicity (especially radiotherapy toxicity), chemoradiotherapy treatment type (concurrent or sequential), depression and anxiety on overall, physical and emotional quality of life (QoL) in long-term breast cancer survivors. Method. We assessed 117 patients (mean follow-up since the end of treatment = 8.1 years) for late radiotherapy toxicity (LENT-SOMA scale), patient and doctor ratings of breast cosmetic outcomes, QoL (EORTC QLQ-C30), depression and anxiety (Hospital and Anxiety Depression scale). RESULTS In univariate analyses, factors associated with significantly decreased QoL were: use of sequential treatment and decreased overall QoL (P = 0.002) and emotional QoL (P = 0.02) ; few radiotherapy late toxicity symptoms (pain and decreased physical QoL, P = 0.01 ; fibrosis and decreased emotional QoL, P = 0.04) ; probable depression or probable anxiety and decreased overall, physical and emotional QoL (P ≤ 0.005). In multivariate analyses, probable depression and probable anxiety were the most stronger predictors for decreased QoL in the overall, physical and emotional domains (P ≤ 0.02). CONCLUSION Improving screening for and treatment of depression and anxiety might improve QoL in long-term breast cancer survivors.

Comparison between two different algorithms used for pretreatment QA via aSi portal images

Several algorithms exist to perform quality assurance for volumetric‐modulated arc therapy (VMAT) treatments based on electronic portal imaging devices (EPID). These algorithms are used to compare doses (convert into water, GLAaS) and fluences (in amorphous silicon (aSi), Varian portal dosimetry). The aim of this study is to compare the two methods using clinical data. In this study, Varian portal dosimetry (VPD) and Epiqa solutions were compared. We used a same set of patient images data treated with 6 MV and 20 MV photon energies and different locations. The response of the portal imaging device was also investigated with different field sizes, monitor units, dose rates, sag effect, and linac daily output. All images were acquired on an electronic portal imaging device (EPID) positioned at source detector distance (SDD) of 100 cm. A virtual water phantom was used for Epiqa to calculate the dose matrices at the maximum depth doses dmax. The 2D gamma evaluation index (GAI) was performed to quantitatively compare the results given by the two solutions. The response of the EPID gave a good agreement with Epiqa (deviation less than 1%) for MU greater than 20 for both 6 MV and 20 MV photon energies. For VPD, the upward sloping trend showed a good agreement for MU higher than 50. Dose rate evaluations for both methods gave a deviation of, respectively, 0.4 and 0.5 % for 6 MV and 20 MV. The gamma criteria of 3 mm for distance to agreement and 3 % for dose difference was, as mean ±1 SD, 99.81%±1.48% and 99.42%±0.97% for VPD and Epiqa, respectively, for 6 MV photon energy. The mean values of the gamma criteria for the collected data using 20 MV photon energy were, respectively, 98.33%±2.41% and 98.12%±1.99% for VPD and Epiqa. The output constancy deviation correction (a 10×10 cm2 reference field plan to obtain absorbed dose despite the linac monitor daily variations) showed a mean deviation of, respectively, 0.07%±0.57% and 0.16%±1.38% for 6 MV and 20 MV photon energies. For sag effect, a slight improvement was noticed for realignment of the integrated image and was 0.25%±0.69% for 6 MV and 0.40%±0.57% for 20 MV. The clinical data were used for pretreatment QA with the two systems, both VPD and Epiqa software, showed acceptable and similar results for low and high energies. Furthermore, Epiqa shows better linearity response for low MU. PACS number: 87.53.Bn, 87.55.km, 87.57.uq

Impact des complications tardives de la radiothérapie, de la dépression et de l’anxiété sur la qualité de vie à long terme dans le cancer du seinImpact of late treatment-related radiotherapy toxicity, depression, and anxiety on quality of life in long-term breast cancer survivors

INTRODUCTION This study aimed to assess the impact of late treatment toxicity (especially radiotherapy toxicity), chemoradiotherapy treatment type (concurrent or sequential), depression and anxiety on overall, physical and emotional quality of life (QoL) in long-term breast cancer survivors. Method. We assessed 117 patients (mean follow-up since the end of treatment = 8.1 years) for late radiotherapy toxicity (LENT-SOMA scale), patient and doctor ratings of breast cosmetic outcomes, QoL (EORTC QLQ-C30), depression and anxiety (Hospital and Anxiety Depression scale). RESULTS In univariate analyses, factors associated with significantly decreased QoL were: use of sequential treatment and decreased overall QoL (P = 0.002) and emotional QoL (P = 0.02) ; few radiotherapy late toxicity symptoms (pain and decreased physical QoL, P = 0.01 ; fibrosis and decreased emotional QoL, P = 0.04) ; probable depression or probable anxiety and decreased overall, physical and emotional QoL (P ≤ 0.005). In multivariate analyses, probable depression and probable anxiety were the most stronger predictors for decreased QoL in the overall, physical and emotional domains (P ≤ 0.02). CONCLUSION Improving screening for and treatment of depression and anxiety might improve QoL in long-term breast cancer survivors.

Estramustine : quelle place en 2010 dans le cancer du sein métastatique ?

Management of breast cancer remains difficult, especially in themetastatic phase. Estramustine may represent an additional therapeutic option, due to an appropriate mechanism of action and significant results in phase II trials: an objective response was obtained in 17.5–47% of cases, with estramustine alone or in combination with docetaxel in advanced metastatic cancers. In addition, estramustine is administered orally and its cost is low. Further studies are mandatory to assess this drug in association with targeted therapies and optimize the benefit/risk ratio, in defining the best prophylactic strategy to decrease the incidence of thrombotic events.RésuméLe cancer du sein continue à poser des problèmes de prise en charge, notamment au stade métastatique. L’estramustine (EM) fait partie des molécules qui peuvent élargir la gamme des options thérapeutiques, en raison d’un rationnel pharmacologique pertinent et de résultats encourageants obtenus au cours d’études de phase II, en monothérapie ou en association au docétaxel, dans des cancers métastatiques (taux de réponse objective compris entre 17,5 et 47 %). De plus, cette molécule a l’avantage d’être administrée par voie orale, avec un coût faible. Des études sont nécessaires pour évaluer l’EM en association aux thérapies ciblées et optimiser le rapport bénéfice/risque en définissant la meilleure stratégie de prévention des accidents thromboemboliques.

Avancées en radiothérapie externe des cancers du sein

In the adjuvant setting, whole breast radiotherapy is the standard of care. Quality assurance (QA) is required in all steps before the start of irradiation using a relatively standardized 3D-conformal technique. The use of new advanced radiation technology and recent devices is in question for increasing the benefit/risk ratio. Currently, many aspects such as QA and indications have to be defined before the routine use of these techniques for curing many cancers including breast cancer. In breast cancer, feasibility of new techniques have been demonstrated in series that included a small number of patients. The challenge is to demonstrate their impact on long-term toxicity decrease, better outcome and to determine the subgroups of patients who will benefit in the context of the association of innovative therapies.RésuméEn situation adjuvante, la radiothérapie (RT) de la glande mammaire en totalité est le gold standard après chirurgie conservatrice. Le contrôle de qualité est requis à toutes les étapes de la procédure. La technique d’irradiation mammaire (± les aires ganglionnaires) est relativement bien standardisée, et l’apport du scanner dans la définition des volumes et l’optimisation des traitements est une avancée considérable de la RT conformationnelle en 3D. Devant le développement technologique, la question de l’utilisation de la modulation d’intensité et de la haute technicité pour améliorer encore plus le ratio bénéfice/risque est posée. Actuellement, les règles de bonnes pratiques, en termes d’indications, de fréquence d’utilisation et de contrôle de qualité de ces techniques innovantes restent à définir pour de nombreux types de cancers, y compris le cancer du sein. La faisabilité est démontrée pour la majorité des nouvelles techniques dans des séries limitées de patientes atteintes de cancer du sein, il reste à démontrer leur impact sur la réduction des toxicités à distance, l’amélioration de la survie et la détermination des patientes qui en bénéficieront le plus dans un contexte de traitements et d’associations thérapeutiques de plus en plus innovants.

Role of the general practitioner in the care of BRCA1 and BRCA2 mutation carriers: General practitioner and patient perspectives

General practitioners (GPs) have an increasing role in referring patients with putative mutation in BRCA1/2 genes for genetics consultation and for long‐term follow‐up of mutation carriers.

Guidelines for reporting secondary findings of genome sequencing in cancer genes: the SFMPP recommendations

In oncology, the expanding use of multi-gene panels to explore familial cancer predisposition and tumor genome analysis has led to increased secondary findings discoveries (SFs) and has given rise to important medical, ethical, and legal issues. The American College of Medical Genetics and Genomics published a policy statement for managing SFs for a list of genes, including 25 cancer-related genes. Currently, there are few recommendations in Europe. From June 2016 to May 2017, the French Society of Predictive and Personalized Medicine (SFMPP) established a working group of 47 experts to elaborate guidelines for managing information given on the SFs for genes related to cancers. A subgroup of ethicists, lawyers, patients’ representatives, and psychologists provided ethical reflection, information guidelines, and materials (written consent form and video). A subgroup with medical expertise, including oncologists and clinical and molecular geneticists, provided independent evaluation and classification of 60 genes. The main criteria were the “actionability” of the genes (available screening or prevention strategies), the risk evaluation (severity, penetrance, and age of disease onset), and the level of evidence from published data. Genes were divided into three classes: for class 1 genes (n = 36), delivering the information on SFs was recommended; for class 2 genes (n = 5), delivering the information remained questionable because of insufficient data from the literature and/or level of evidence; and for class 3 genes (n = 19), delivering the information on SFs was not recommended. These guidelines for managing SFs for cancer-predisposing genes provide new insights for clinicians and laboratories to standardize clinical practices.

Innovations et recherche en radiothérapie en France

Significant advances in radiation therapy have recently been observed. Important technological advances allow for greater precision in defining target volumes and organs at risk, which will certainly impact the risk/benefit ratio for cancer care, particularly in the new setting of therapeutic associations using new drugs. Despite the major role of radiation therapy in the multidisciplinary management of several cancers, pharmaceutical industry support for radiation therapy trials that do not involve drugs remains nil. Thus, grant applications for radiotherapy studies are mainly oriented towards institutional clinical research. At the same time, research in radiation therapy has changed considerably. In France, since the beginning of the year 2000, the Cancer Institute (INCa) has considered radiation oncology modernisation as one of the health priorities. In their programs, substantial grants have been allocated to the evaluation of innovative techniques, including financial issues and their potential generalisation throughout the country. Funding for clinical research programs has also been allocated to significant projects that will impact future clinical practice. In this article, we aim to describe the various plans for restructuring radiation therapy in France, and make an inventory of the innovative projects in clinical and technology research that involve public and private institutions.RésuméLa radiothérapie a connu un essor formidable grâce aux évolutions technologique et informatique. Il est possible de mieux définir les volumes cibles et les organes à risque et, par conséquent, d’imposer des contraintes de doses et de volumes permettant une épargne des tissus sains et une amélioration du ratio bénéfice/risque. Ce dernier pourrait se révéler primordial dans le cadre des associations aux nouvelles molécules. Dans ce contexte d’évolution, la recherche clinique et technologique en radiothérapie a connu une avancée considérable. Cependant, malgré la place capitale qu’occupe la radiothérapie dans la prise en charge multidisciplinaire de nombreux cancers, les moyens mis à sa disposition par l’industrie pharmaceutique sont incomparables à ceux dont bénéficie l’oncologie médicale. Ce support limité (voire inexistant) aux essais de radiothérapie, n’impliquant pas les traitements médicaux, contribue largement à orienter les demandes de financements vers la recherche institutionnelle. Dans le cadre du Plan cancer et sous l’impulsion de l’INCa, de nombreux projets ont vu le jour. Ainsi, parallèlement à la modernisation des plateaux techniques de radiothérapie en France, les financements alloués dans le cadre des programmes de soutien aux techniques innovantes et coûteuses (STIC) ont permis de réaliser une évaluation de nombreuses techniques de radiothérapie moderne passées en routine dans de nombreux pays dans lemonde. La radiothérapie a également bénéficiéde nombreux PHRC ayant permis une recherche clinique de pointe posant des questions pertinentes non résolues pour la pratique quotidienne. Dans cet article, nous ferons le point sur les avancées de la radiothérapie française en termes de restructuration et de projets innovants en recherche clinique et technologique dans les secteurs publics et privés.