Search

PURPOSE To describe the quality assurance (QA) program and early toxicities in the phase III randomized trial BONBIS (NCT00907868) on the role of a localized radiation boost in ductal carcinoma in situ (DCIS). MATERIALS AND METHODS From November 2008 to July 2014, 2004 patients were randomized in arm A (only whole breast radiotherapy, WBRT) and arm B (WBRT + boost). The QA program involved 44 participant centers that performed the dummy run (DR). Compliance and uniformity of clinical target volume (CTV) delineations, and dose prescription and delivery according to the BONBIS trial radiotherapy guidelines were analyzed. Acute toxicities (during and up to 3 months after radiotherapy completion, NCI-CTCAE v3.0 classification) were evaluated in 1929 patients. RESULTS The differences in whole breast CTV (CTV1) and planning target volume (PTV1) were ≤10%, and the differences in boost CTV (CTV2) and PTV (PTV2) were ≥20% compared with the reference DR values; 95% of the prescribed dose encompassed 98.7% and 100% of the median CTV1 and CTV2. Grade ≥2 breast erythema (38.3% vs. 22.4% of grade 2 and 5.4% vs. 2.1% of grade 3, p

International audience; Background: Rate of abdominoperineal resection (APR) varies from countries and surgeons. Surgical impact of preoperative treatment for ultra-low rectal carcinoma (ULRC) initially indicated for APR is debated. We report the 10-year oncological results from a prospective controlled trial (GRECCAR 1) which evaluate the sphincter saving surgery (SSR).Methods: ULRC indicated for APR were included (n = 207). Randomization was between high-dose radiation (HDR, 45 + 18 Gy) and radiochemotherapy (RCT, 45 Gy + 5FU infusion). Surgical decision was based on tumour volume regression at surgery. SSR technique was standardized as mucosectomy (M) or partial (PISR)/complete (CISR) intersphincteric resection.Results: Overall SSR rate was 85% (72% ISR), postoperative morbidity 27%, with no mortality. There were no significant differences between the HDR and RCT groups: 10-year overall survival (OS10) 70.1% versus 69.4%, respectively, 10.2% local recurrence (9.2%/14.5%) and 27.6% metastases (32.4%/27.7%). OS and disease-free survival were significantly longer for SSR (72.2% and 60.1%, respectively) versus APR (54.7% and 38.3%). No difference in OS10 between surgical approaches (M 78.9%, PISR 75.5%, CISR 65.5%) or tumour location (low 64.8%, ultralow 76.7%).Conclusion: GRECCAR 1 demonstrates the feasibility of safely changing an initial APR indication into an SSR procedure according to the preoperative treatment tumour response. Long-term oncologic follow-up validates this attitude.

Adjuvant radiotherapy is one of the major anticancer treatments in early breast cancer patients. Acute and late radio-induced effects may occur during or after breast cancer radiotherapy, and their medical management is a major issue for radiation oncologists. Here, the present review of literature embraces complementary non-pharmacological interventions, which could be combined to adjuvant radiotherapy in order to improve patients care.

Tailored neoadjuvant treatment of locally advanced rectal cancer (LARC) may improve outcomes. The aim of this study was to determine early MRI prognostic parameters with which to stratify neoadjuvant treatment in patients with LARC.All patients from a prospective, phase II, multicentre randomized study (GRECCAR4; NCT01333709) were included, and underwent rectal MRI before treatment, 4 weeks after induction chemotherapy and after completion of chemoradiotherapy (CRT). Tumour volumetry, MRI tumour regression grade (mrTRG), T and N categories, circumferential resection margin (CRM) status and extramural vascular invasion identified by MRI (mrEMVI) were evaluated.A total of 133 randomized patients were analysed. Median follow-up was 41·4 (95 per cent c.i. 36·6 to 45·2) months. Thirty-one patients (23·3 per cent) developed tumour recurrence. In univariable analysis, mrEMVI at baseline was the only prognostic factor associated with poorer outcome (P = 0·015). After induction chemotherapy, a larger tumour volume on MRI (P = 0·019), tumour volume regression of 60 per cent or less (P = 0·002), involvement of the CRM (P = 0·037), mrEMVI (P = 0·026) and a poor mrTRG (P = 0·023) were associated with poor outcome. After completion of CRT, the absence of complete response on MRI (P = 0·004), mrEMVI (P = 0·038) and a poor mrTRG (P = 0·005) were associated with shorter disease-free survival. A final multivariable model including all significant variables (baseline, after induction, after CRT) revealed that Eastern Cooperative Oncology Group performance status (P = 0·011), sphincter involvement (P = 0·009), mrEMVI at baseline (P = 0·002) and early tumour volume regression of 60 per cent or less after induction (P = 0·007) were associated with relapse.Baseline and early post-treatment MRI parameters are associated with prognosis in LARC. Future preoperative treatment should stratify treatment according to baseline mrEMVI status and early tumour volume regression.El tratamiento neoadyuvante personalizado del cáncer de recto localmente avanzado (locally advanced rectal cancer, LARC) puede mejorar los resultados. El objetivo de este estudio fue determinar factores pronósticos precoces mediante RMN para estratificar el tratamiento neoadyuvante en pacientes con LARC. MÉTODOS: Todos los pacientes de un eensayo prospectivo de fase II, multicéntrico y aleatorizado (GRECCAR4-NCT01333709) se incluyeron en este estudio y se les realizó una RMN antes del tratamiento, 4 semanas después de la quimioterapia de inducción y después de completar la quimiorradioterapia (chemoradiation, CRT). Se evaluó la volumetría tumoral, el grado de regresión tumoral mediante RMN (MRI Tumor Regression Grade, mrTRG), la estadificación T, la estadificación N, el estado del margen de resección circunferencial (circumferential resection margin, CRM) y la presencia de invasión extramural vascular en la RMN (extramural vascular invasion, mrEMVI).Se analizaron 133 pacientes aleatorizados. La mediana de seguimiento fue de 41,4 meses (i.c. del 95%: 36,6-45,2). En 31 pacientes (23%) se diagnosticó una recidiva. En el análisis univariado de la situación basal, mrEMVI fue el único factor pronóstico asociado con un peor resultado (P = 0,0152). Después de la quimioterapia de inducción, un volumen tumoral más alto en la RMN (P = 0,019), una regresión del volumen tumoral ≤ 60% (P = 0,002), la afectación del CRM (P = 0,037), mrEMVI (P = 0,026) y un grado escaso mrTRG (P = 0,023) se asociaron con un mal resultado. Después de completar la CRT, la ausencia de respuesta completa en la RMN (P = 0,004), la presencia de mrEMVI (P = 0,04) y una insuficiente mrTRG (P = 0,005) se asociaron con una supervivencia libre de enfermedad más corta. En el modelo multivariable final en el que se incluyeron todas las variables significativas (basales, postinducción, post-CRT), el estado de ECOG (P = 0,011), la afectación esfinteriana (P = 0,009), la presencia de EMVI al inicio (P = 0,002) y una regresión precoz del volumen tumoral ≤ 60% después de la inducción (P = 0,007) se asociaron con una recidiva. CONCLUSIÓN: Los parámetros basales y post-tratamiento precoces de la RMN se asocian con el pronóstico en el LARC. La estrategia terapéutica preoperatoria futura deberá estratificar el tratamiento de acuerdo con la presencia de EMVI al inicio y la regresión precoz del volumen tumoral.

Background and Purpose: Recent phase 3 clinical trials have evaluated the addition of bevacizumab (B) to standard chemotherapy in the treatment of patients with non-metastatic breast cancer. But few data are available about the tolerance of B with locoregional radiation therapy (RT). The objective was to evaluate the 5 years late toxicities of the concurrent B and RT in non-metastatic breast cancer. Material and methods: This is a multicenter prospective study including non-metastatic breast cancer patients enrolled in phase 3 clinical trials evaluating B with concurrent RT (BEATRICE, BETH, BEVERLY 1, BERVERLY 2) versus RT alone. All patients received neo-adjuvant or adjuvant chemotherapy and normo-fractionated breast or chest wall RT, with or without regional lymph nodes RT. B was administrated as an equivalent of 5 mg/kg every week for 1 year. The safety profile (using the Common Terminology Criteria for Adverse Events version 3.0) was evaluated at 1, 3 and 5 years after the completion of radiotherapy. Results: From October 2007 to January 2012, 151 patients totally included. Median follow-up was 60 months (36-84) and 5 years late toxicities were available for 104 patients (46 with B and RT, 58 with RT alone). Median age was 51 (22-81). 61% of patients received regional lymph nodes RT. The majority of tumor was triple negative (65.6%), tumor size Conclusion: Concurrent B and locoregional RT provides acceptable 5-years toxicities in patients with non-metastatic breast cancer. No grade ≥3 toxicity was observed. Citation Format: Clément-Zhao A, Tanguy M-L, Cottu P, De La Lande B, Bontemps P, Lemanski C, Baumann P, Levy C, Peignaux K, Reynaud-Bougnoux A, Gobillion A, Kirova Y. TOxicities of Locoregional Radiotherapy Associated with Bevacizumab in patients with non-metastatic breast cancer (TOLERAB): Final long-term evaluation [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-12-06.

This phase III trial included patients with ultra-low rectal adenocarcinoma that initially required abdominoperineal resection. The surgical decision was based on clinical tumour status after preoperative treatment. The overall sphincter-saving resection rate was 85 per cent, with 72 per cent rate of intersphincteric resection. Long-term results showed that changing the initial abdominoperineal resection indication into a sphincter-saving resection according to tumoral response is oncologically safe. Saving the sphincter

To evaluate our long-term experience on one-day breast intraoperative radiotherapy (IORT) given as sole radiation treatment to selected patients with breast cancer.Inclusion criteria of INTRAOBS study (prospective observational study) were: ER+ T1N0 unifocal ductal carcinoma; absence of lymphovascular invasion or of extensive intraductal component (Scarff-Bloom-Richardson grade III and HER2+++ excluded). Two different linacs were used (20Gy/1 fraction): one dedicated electron linac (October 2011), and afterwards a mobile linac (50kV photons). The primary endpoint was the local recurrence rate (=ipsilateral breast cancer recurrences number). Secondary endpoints were recurrence-free survival (RFS), overall and specific survival, cosmetic results, and patient satisfaction.Of the present pre-planned analysis for the first 200 patients (median age: 68 years; range, 59-87 years) who received IORT between January 2010 and October 2014 (median follow-up of 53.4 months). A total of 193 patients were still alive. The local recurrence rate was 2.5% (n=5). The 1- and 5-year local RFS rates were 100% and 95.2%, respectively. At 12 months post-surgery, satisfaction about IORT was excellent for 86.9% of patients. Cosmetic results were considered by patients and physicians as good or very good in 89.4% and 97.3% of cases, respectively.IORT for selected patients with breast cancer shows low recurrence rates, good cosmetic outcomes and excellent satisfaction.

Purpose To determine the 3 years late toxicity among patients with non-metastatic breast cancer who received concurrent bevacizumab and locoregional radiotherapy. Material and methods This is a single-arm, multicentre, prospective study, of the toxicity of adjuvant concomitant association of bevacizumab and radiotherapy in patients with breast cancer. Toxicity was assessed by the Common Terminology Criteria for Adverse Events version 3.0 during the radiotherapy and follow-up clinics at 12 and 36 months after its completion. The study was designed to evaluate the toxicity at one year, 3 years and 5 years. Results Sixty-four patients were included from October 2007 to August 2010. All of them received concurrent adjuvant radiotherapy and bevacizumab (in 24 cases after primary systemic treatment). All patients received non-fractionated radiotherapy to breast or chest wall with or without irradiation of regional lymph nodes. Early toxicity has been previously reported. Median follow-up was 46.4 months (range: 18–77 months). Median age was 53 years old (range: 23–68 years). The 3-years overall survival was 93% (range: 87–100%). Evaluation of the toxicity at 3 years was available for 67% of the patients. There was a low rate of toxicity: 14% grade 1 pain, 9% grade 1 fibrosis, 2% grade 1 telangiectasia, 2% grade 1 paresis, 7% grade 1 lymphedema and 2% grade 3 lymphedema. No grade 4 toxicity was observed. No patient had a left ventricular ejection fraction below 50% at 3 years. Conclusions Concurrent bevacizumab with locoregional radiotherapy is associated with acceptable 3-years toxicity in patients with breast cancer.

Purpose/Objectives The purpose of this study was to determine early and late toxicities among patients with non-metastatic breast cancer (BC) receiving concurrent bevacizumab (BV) and radiation therapy (RT). Materials/Methods Multicentre, prospective study, of the toxicity of adjuvant concomitant association of BV and RT in patients with non-metastatic BC enrolled in Phase 3 BEATRICE, BEVERLY and BETH trial. Early and late toxicities were assessed by the Common Terminology Criteria for Adverse Events v. 3.0 during RT, 12 months and 36 months after its completion. Results Sixty-four patients were included from october 2007 to august 2010. They all received adjuvant RT and BV concomitant treatment, plus neo-adjuvant BV for 24 patients. RT was adjuvant and normo-fractionated. Twelve months toxicity was available for 60 patients and 36 months toxicity was available for 43 patients. Median follow-up was 46 months (18-77). Median age was 51 years old (23-68). Among 63 evaluated patients during RT, acute radiation dermatitis was observed in 48 (76%) patients : Grade 1 for 27 (43%), grade 2 for 17 (27%), grade 3 for 4 patients (6%). Grade 2 acute oesophagitis was observed in 1 patient. At 3 years, few toxicities were observed : 6 patients (14%) had grade 1 pain, 4 (9%) had grade 1 fibrosis, one (2%) had grade 1 telangiectasis, one (2%) had grade 1 paresis, 3 (7%) had grade 1 lymphoedema and one grade 3 lymphoedema. No grade 4 toxicity was observed. At 12 months, only one evaluated patient had a LVEF Conclusions Concurrent bevacizumab with locoregional RT is associated with acceptable early and late 3-years toxicities in patients with BC. Determination of late toxicity at 60 months is currently underway. Citation Format: Dautruche A, Belin L, Cottu P, Bontemps P, Lemanski C, De La Lande B, Baumann P, Missohou F, Levy C, Peignaux K, Reynaud-Bougnoux A, Denis F, Gobillion A, Ady Vago N, Fourquet A, Kirova Y. Radiotherapy associated with concurrent bevacizumab in patients with non-metastatic breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-10-17.

Standard of care in breast cancer management is well-defined. However, some gray zones still exist, in particular adjuvant radiotherapy indications in case of pN1mi breast cancer. Here we propose to define their prognosis, to underpin the benefit of adjuvant treatments in such patients' management and to define lymphedema risk, which is the most common late side effect of locoregional treatments.

Randomized trials demonstrated similar overall survival between mastectomy and breast-conservative surgery followed by adjuvant radiation therapy. Breast-conservative surgery, with adjuvant radiation therapy, with or without neoadjuvant systemic therapy has become the standard of care for women with early or locally advanced breast cancer. Nevertheless, certain cardiac, lung or cutaneous toxicities may alter the long-term body image and the quality of life of a limited number of patients who consider having had "overtreatment" or treatment outside the best knowledge of science. In case of low-risk breast cancer, several trials have evaluated the carcinologic outcome in absence of radiation therapy after breast-conservative surgery. Local recurrences increased in case of breast-conservative surgery alone but without impact on overall survival. Multiple debates have emerged in order to select the most appropriate evaluation criteria. Finally, a large consensus has considered that reducing local recurrences is important but with modern technologies and after identifying patients of individual radiosensitivity. Indeed, in case of a low absolute risk of local recurrence, radiation therapy techniques have been developed to allow a focal treatment especially for patients with high risk of developing late effects. This kind of compromise takes into account the reduction risk of local recurrences but also the probability of developing radiation-induced cutaneous sequelae. In the same way, for patients considered at high risk of recurrence, the huge volumes need specific techniques to better cover the targets while protecting the surrounding critic organs such as heart and lung. Intensity-modulated radiation therapy and the local high boost may help to decrease local recurrences of these more extended and aggressive diseases while considering the individual radiosensitivity that paves the way of long-term sequelae. In this article, we detail a personalized approach of breast radiation therapy considering the absolute risk of local recurrences and the probability of radiation-induced toxicity appearance.

Resume Nous proposons dans cette revue de rapporter l’impact de la radiotherapie stereotaxique chez les patients ayant un cancer oligometastatique ou en oligoprogression en termes de survie sans progression metastatique et globale, et d’identifier quelle est la place de cette modalite de radiotherapie au sein du parcours–patient.

Ambulatory surgery has originally become possible in breast cancer, thanks to an earlier diagnosis of the disease and less aggressive surgery as well as technological innovations in surgery and anesthesia. At the same time, there was an evolution of mentalities encouraging greater patient autonomy. Its development in France is of major political concern. Above its economical impact, the key point is mostly the patient capacity of a better recovery through a more active management. Furthermore, ambulatory surgery is time-efficient, thus fits very well with today’s way of life.

Adjuvant radiotherapy significantly reduces locoregional recurrences in breast cancer at any stage, from in situ stage to locally advanced tumors, and improves specific survival after conservative surgery or mastectomy for tumors. After decades of uniform external irradiation, technical improvements have dramatically changed the quality of treatment and new technologies now allow therapeutic climbing, offering a wider coverage of volumes with lower toxicities. Early stages tumors can also beneficiate from a drastic de-escalation, by reducing volume, dose, or duration of the radiation treatment. These new schemes are more easily accepted and improve quality of life. “One fits all” times are gone and now each woman must have her personalized radiotherapy.

IF 4.942 (2017); International audience

Les dernieres RPC sur le traitement neoadjuvant du cancer du rectum dataient de 2005. Elles ont ete mises a jour en integrant les dernieres publications. Pour les tumeurs T3 ou T4, une IRM est recommandee pour preciser la marge circonferentielle. Aucun des examens d’imagerie ne peut predire avec precision le statut ganglionnaire. La RT preoperatoire diminue le taux de recidive locale mais altere le resultat fonctionnel digestif et la fonction sexuelle apres chirurgie conservatrice. Les cancers du haut rectum resecables d’emblee ne doivent pas beneficier d’un traitement neoadjuvant. Pour les tumeurs du tiers moyen et du tiers inferieur du rectum, l’indication depend de l’evaluation en imagerie. Certaines tumeurs avec une bonne marge circonferentielle peuvent etre traitees par chirurgie d’emblee. Les tumeurs mrT3d et T4 doivent beneficier d’une radiochimiotherapie. La CT associee a la RT repose sur le 5FU oral (capecitabine). L’utilisation du FU IV est une alternative possible. Il n’y a pas d’interet a ajouter une autre molecule de chimiotherapie. Apres RT courte, la chirurgie doit etre realisee au maximum 7 jours suivants l’irradiation. Apres CTRT, il ne semble pas necessaire de prolonger le delai d’attente au dela de 6-8 semaines.

In addition to achieve breast conserving surgery after neoadjuvant chemotherapy, its indications are growing, especially in Her2 overexpressing and triple negative breast cancers owing to the emergence of new targeted therapies. Radiotherapy belongs to breast cancer management. However, some questions are still unresolved regarding nodes area irradiation after neoadjuvant chemotherapy. This short communication reviews indications of radiotherapy of node areas in breast cancer after neoadjuvant chemotherapy.

Irradiation of node areas is still a complex challenge in external radiotherapy for breast cancer. Acceptable target coverage is always balanced by protection of organs at risk and patient morphology. Intensity-modulated radiotherapy increases the quality of dose distribution on the planning target volume, but modifies dramatically the irradiation coverage of critical structures in a different way compared to 3D treatment. In this paper we analyze this new technique in breast treatment with node regions, its expected gain and potential risks.

International audience; Aim: Women of reproductive age with breast cancer generally receive gonadotoxic chemotherapy. Fertility issues are of great concern for them. However, little is known on ovarian damage during chemotherapy and its evolution during long-term follow-up. The Anti-Mü llerian hormone; Ovarian reserve; Amenorrhea aim of this study was to provide a detailed description of serum anti-Mü llerian hormone (AMH) evolution during chemotherapy and 24-month follow-up.Methods: This prospective cohort study was conducted in 250 patients, aged 18e39 years, diagnosed with breast cancer and treated with adjuvant/neoadjuvant chemotherapy. Each patient underwent blood AMH measurement at each chemotherapy cycle, and at 6, 12 and 24 months after chemotherapy. Menses occurrence was also recorded.Results: Mean basal AMH level was 4.19 AE 4.84 ng/mL, and was negatively correlated with age. Serum AMH level rapidly decreased in all patients after each chemotherapy cycle to undetectable levels in most of them, and slowly increased in 45% of the patients during the 24-month follow-up. AMH decrease was significantly associated with age and basal AMH level, but not with cyclophosphamide dose and tamoxifen use. The prevalence of chemotherapy-related amenorrhoea was 92.4% at the end of chemotherapy; women with amenorrhoea being significantly older and having lower basal AMH than women who resumed menses.Conclusions: Our study confirms rapid and deep ovarian reserve alteration in young women receiving chemotherapy for breast cancer, and shows moderate AMH recovery in some patients. Although AMH cannot alone predict fertility potential, these new data emphasise the need for post-treatment ovarian insufficiency follow-up, strongly support the use of fertility preservation strategies and may provide new tools for improved counselling.

IF 4.328; International audience

Hormone receptors are expressed in more than 75% of breast cancer. Therefore, two prescription modalities of endocrine therapy could be proposed: either sequential or concomitant to breast cancer irradiation. If combined to radiotherapy, is endocrine therapy a radiosensitizer? Does endocrine therapy enhance the risk factor of radio-induced toxicity? Here, we will distinguish the interaction of ionizing radiation combined with therapies targeting oestrogen receptor (REα) from the interaction of ionizing radiation with oestrogen. This review aims at making clear all these items.

Resume Le traitement en un jour du cancer du sein se definit par l’association d’une chirurgie ambulatoire et d’une irradiation peroperatoire. La selection des patientes et des tumeurs associees a la rigueur du parcours patient assurent son succes. La technique operatoire n’est pas modifiee par l’irradiation peroperatoire. L’evaluation de l’indice de satisfaction des patientes est tres elevee. La moins value financiere actuelle de cette association therapeutique ne doit pas etre un frein a sa mise en place.

Purpose/Objectives Few data are available regarding the safety of the concurrent combination of bevacizumab with adjuvant radiotherapy (RT) in breast cancer, especially in terms of late toxicity. The aim of this study was to determine early and late loco-regional toxicities among patients with non-metastatic breast cancer treated with this combination. Materials/Methods In our prospective and descriptive study, we analyzed loco-regional toxicities of adjuvant RT in patients with non-metastatic breast cancer receiving either concurrent bevacizumab or not in the randomized trial BEATRICE. Early and late toxicities were assessed by the Common Terminology Criteria for Adverse Events (v3.0). Evaluation was done during RT and 12 months after the end of RT. All patients provided written informed consent before enrollment. Statistical analysis was performed to analyze toxicity between the two groups. Results From September 2007 to July 2009, we included 84 patients from the randomized trial BEATRICE which evaluate the efficacy and safety of the addition of bevacizumab to standard adjuvant therapy in patients with triple negative breast cancer; 39 women received an adjuvant RT with concurrent bevacizumab and 45 women received an adjuvant RT alone. Evaluation at 12 months was available for all the patients. All patients had a triple negative non-metastatic breast cancer and had an adjuvant chemotherapy then RT. Among patients receiving concurrent bevacizumab with RT, a total of 35 patients (90%) achieved a whole breast irradiation (median dose: 50 Gy) with a boost in the surgical bed (median dose: 16 Gy) and 4 patients (10%) had a post mastectomy RT (median dose 50 Gy); lymph node RT was performed in 19 patients (49%) with internal mammary chain RT in 12 patients (31%). Mean time of bevacizumab treatment was 11.7 months [2.1-12.6] and mean total dose of bevacizumab was 15000 mg [3330-28080]. Among patients receiving RT alone, 38 patients (84%) achieved a whole breast irradiation (median dose: 50 Gy) with a boost in the surgical bed (median dose: 16 Gy) and 7 patients (16%) had a post mastectomy RT (median dose 50 Gy); lymph node RT was performed in 21 patients (47%) with internal mammary chain RT in 14 patients (31%). Radiation treatment parameters were not significantly different between the two groups. Incidence of acute grade 3 dermatitis was 10% in patients receiving bevacizumab associated with RT and 6% in patients receiving RT alone without significant difference. One year after the end of RT, the most common late toxicities in the group receiving bevacizumab and RT were grade 1-2 pain (18%), grade 1-2 fibrosis (8%), grade 1-2 arm lymphedema (8%) and grade 1-2 telangiectasia (6%).There was no significant difference in pain, radiation fibrosis, telangiectasia, arm lymphedema and dyspnea between the two groups. No patient experienced grade 3-4 toxicity in the two groups. Conclusions Our results indicate that concurrent bevacizumab with loco-regional RT provide acceptable early and late toxicities after one year in patients with non-metastatic breast cancer. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-14-11.

International audience; Irradiation techniques for breast cancer (arctherapy, tomotherapy) are evolving and intensity-modulated radiation therapy is being increasingly considered for the management of these tumours. Here, we propose a review of intensity-modulated radiation therapy planning issues, clinical toxicities and indications for breast cancer.

Intensity modulated radiotherapy (IMRT) is a technique allowing dose escalation and normal tissue sparing for various cancer types. For breast cancer, the main goals when using IMRT were to improve dose homogeneity within the breast and to enhance coverage of complex target volumes. Nonetheless, better heart and lung protections are achievable with IMRT as compared to standard irradiation for difficult cases. Three prospective randomized controlled trials of IMRT versus standard treatment showed that a better breast homogeneity can translate into better overall cosmetic results. Dosimetric and clinical studies seem to indicate a benefit of IMRT for lymph nodes irradiation, bilateral treatment, left breast and chest wall radiotherapy, or accelerated partial breast irradiation. The multiple technical IMRT solutions available tend to indicate a widespread use for breast irradiation. Nevertheless, indications for breast IMRT should be personalized and selected according to the expected benefit for each individual.

RésuméLa prise en charge en urgence de patients présentant un syndrome coronaire aigu (SCA) repose sur un diagnostic clinique et électrocardiographique précis. La stratification initiale du risque est l’étape clé. L’orientation, ultime étape, dépend du degré de l’urgence et de la stratégie de reperfusion envisagée dès la phase pré-hospitalière. La prise en charge d’un patient présentant un SCA nécessite donc une collaboration étroite entre les médecins de l’urgence et les cardiologues selon des protocoles pour un accès facilité au cathétérisme si nécessaire.Les défis de la prise en charge des SCA en pré-hospitalier reposent sur plusieurs facteurs:a)la « maîtrise » par l’urgentiste de nouvelles molécules anti-agrégantes et anticoagulantes pour adapter leurs prescriptions au profil du patient;b)le développement de filières en fonction des spécificités régionales (considérations géographiques et répartition des centres interventionnels) de mutualisations entre les établissements, afin de réduire le temps d’accès aux salles de cathétérisme des patients à haut risque;c)l’organisation en réseau où le SAMU joue un rôle essentiel pour la coordination entre les différents acteurs médicaux;d)l’analyse en routine de l’évolution des pratiques professionnelles en corrélation avec les recommandations de la Haute Autorité de santé;e)et l’intégration de la médecine pré-hospitalière aux programmes de prévention en santé pour mieux décrypter les représentations de la maladie coronaire et encourager les patients et leurs proches à utiliser le « 15 ».SummaryRisk stratification in the prehospital setting is key in the emergency management of patients with acute coronary syndromes (ACS), based on clinical diagnosis and specific electrocardiographic criteria. The orientation is the ultimate stage of this decision support and depends on the degree of urgency and the strategy chosen. The management of ACS patients requires close collaboration between emergency physicians and cardiologists, using simplified protocols to facilitate access to catheterization if judged necessary. Multiple other challenges exist in the prehospital management of ACS:a)‘control’ by emergency physicians of new antiplatelet and anticoagulant molecules, adjusting their prescription to patient profiles;b)the development of clusters based on regional specifics (e.g. geographic considerations and distribution of percutaneous coronary intervention centers) to reduce delay to catheterization in high-risk patients;c)the network organization, where the SAMU is essential for coordination between different medical teams;d)the routine evaluation of evolving practices in terms of quality of care;e)and the integration of prehospital medicine into healthcare programs to better understand the manifestations of coronary artery disease and to encourage patients and their families to use the emergency medical system. The task faced by emergency physicians is to adopt strategies that more closely align to patients’ needs.

Background and purpose: Postoperative whole breast external radiotherapy remains the current standard of care for patients with early operable breast cancer. In the elderly, the low crude numbers of recurrence and the frequency of comorbidities urged teams to investigate the feasibility and the results of intraoperative radiotherapy (IORT) delivered in one fraction during the surgical procedure. Material and methods: 94 patients (> 65 years old) accepted to be included in this phase II trial according to clinical and histopathology criteria and signed the informed consent. Among them, 42 presented all the inclusion criteria, namely pT0-1 pN0, non lobular invasive unifocal carcinoma, margin ≥ 2 mm (assessed during the surgical procedure) and estrogen receptors positivity. All patients were operated upon in a dedicated IORT facility (linear accelerator) located centrally among six operated rooms. After tumor removal, the surgical bed was approximated by sutures to bring the tissue within the radiation target volume. The tumor beds were completely encompassed by 4 to 6 cm circular fields using flattened applicators at a 110 cm distance. One fraction of 21 Gy was prescribed and specified at the 90% isodose using electron with energies ranging from 6 to 10 MeV. In vivo dosimetry was performed for all patients using real-time in vivo semiconductor detectors (PTW) fixed by the surgeon within the surgical bed. A 5 year adjuvant hormonotherapy was prescribed according to the recommendations. Primary end-point was the quality index [QI] - ratio between the prescribed dose and the in vivo measured dose-. Secondary endpoints corresponded to quality of life, local recurrences, cosmetic results, specific and overall survival. Results: Median follow-up is now 54 months [range 12–62]. Median age was 72 years [66-80] and median tumor diameter was 10 mm [3-19 mm]. 36 tumors were grade 1 or 2 and 100 % of the tumors expresses estrogen receptors. All patients received the total prescribed dose. No external postoperative radiotherapy was delivered. Intraoperative dosimetry demonstrated a good accordance between the delivered and the prescribed doses for 97% of the 37 evaluable patients. No acute grade 2 or greater toxicities were observed. Scores for quality of life were collected for all patients and showed no modification between pre and posttreatment evaluations. Late cosmetic result was good to excellent. All patients are still alive and the 4 year-disease-free-survival is currently 97%. Two patients recurred: (i) one infracentimetric superficial recurrence in the border of the surgical bed and close to the skin (at 18 months) (ii) a second primary tumor in another quadrant (at 6 months). These two patients underwent salvage mastectomy and are free of disease at the time of analysis. Conclusion: For a very selected population, these results confirm that partial breast IORT with electrons may be considered as an interesting alternative to the standard 6-weeks radiotherapy, offering therefore a safe one-step procedure treatment. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-13-12.

Background Ductal carcinoma in situ is defined as breast cancer confined to the ducts of the breast without evidence of penetration of the basement membrane. Local treatment quality represents one of the most prognostic factors as half of recurrences are invasive diseases. The main goal of adjuvant radiotherapy after conservative surgery is to decrease local recurrences and to permit breast conservation with low treatment-induced sequelae. Several randomized trials have established the impact of 50 Gy to the whole breast (WB) in terms of local control. Nevertheless, no randomized trial is still available concerning the role of the boost in this disease. The phase III randomized trial “BONBIS” is elaborated to evaluate the impact of a 16-Gy boost after 50 Gy delivered to the whole breast in 25 fractions and 33 days. Methods: A total of 1950 patients DCIS breast cancer patients are planned to be enrolled in this trial. Patients will receive the following treatment: (A) WB radiotherapy of 50 Gy in 25 fractions vs. (B) WB radiotherapy of 50 Gy in 25 fractions plus a localized 16-Gy boost in 8 fractions. The primary endpoint is local-relapse free survival (LRFS). This trial is designed to detect an expected rate in control arm of 7% and 4 % in experimental arm. With 90% power and a=0.05, 137 events are necessary to achieve the main goal. An interim analysis is planned after 50% of observed event. Stratifications are made based on recognized prognostic factors: age, hormonal treatment, differentiation, circumstance of diagnosis, surgical margin, centre. Secondary endpoints are relapse free survival, overall survival, acute and late toxicities, cosmetic results, and quality of life. Translational researches are also planned to identify intrinsic radiosensitivity of normal tissues (radiation-induced apoptosis assay, genome-wide association study) but also predictive models of tumor recurrences. Inclusions have started in November 2008 and are not so far than the planned estimation. This trial is granted by the French National Cancer Institute (PHRC 2008) and supported by the French National Society of Radiation Oncology (SFRO). Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT2-06-01.

Ductal carcinoma in situ is defined as breast cancer confined to the ducts of the breast without evidence of penetration of the basement membrane. Local treatment quality represents one of the most prognostic factors as half of recurrences are invasive diseases. The main goal of adjuvant radiotherapy after conservative surgery is to decrease local recurrences and to permit breast conservation with low treatment-induced sequelae. Several randomized trials have established the impact of 50 Gy to the whole breast in terms of local control. Nevertheless, no randomized trial is still available concerning the role of the boost in this disease. In this review, we present updated results of the literature and we detail the French multicentric randomized trial evaluating the impact of a 16 Gy boost after 50 Gy delivered to the whole breast in 25 fractions and 33 days. This protocol will start inclusions in October 2008.

Combined radiation and hormone therapies have become common clinical practice in recent years for locally-advanced prostate cancers. The use of such concomitant therapy in the treatment of breast disease has been infrequently reported in the literature, but seems justified given the common hormonal dependence of breast cancer and the potential synergistic effect of these two treatment modalities. As adjuvant therapy, two strategies are used in daily clinical practice: upfront aromatase inhibitors or sequentially after a variable delay of tamoxifen. These molecules may, thus, interact with radiotherapy. Retrospectives studies recently published did not show any differences in terms of locoregional recurrences between concurrent or sequential radiohormonotherapy. Lung and skin fibroses due to concurrent treatment are still under debate. Nevertheless, late side effects appeared to be increased by such a treatment, particularly in hypersensitive patients identified at risk by the lymphocyte predictive test. Concurrent radiohormonotherapy should, thus, be delivered cautiously at least for these patients. This article details the potent advantages and risks of concurrent use of adjuvant hormonotherapy and radiotherapy in localized breast cancers.

International audience; BACKGROUND:Accelerated partial breast irradiation (APBI) is an option for adjuvant radiotherapy according to ASTRO and ESTRO recommendations. Among the available techniques, volumetric-modulated arc therapy (VMAT) is attractive but has not been extensively studied for APBI. This study assessed its feasibility, tolerance and early oncological outcomes.METHODS:We analysed the data of nine patients (median age 74 years) with ten lesions (one bilateral cancer) treated from May 2011 to July 2012 with APBI using VMAT. The radiation oncologist delineated the surgical tumour bed, and added an 18 mm isotropic margin to obtain the planning target volume (PTV). The dose was 40 Gy prescribed in 4 Gy fractions given twice a day over five days. Patients were regularly followed for toxicities and oncological outcomes.RESULTS:Mean PTV was 100.0 cm(3) and 95 % of the PTV received a mean dose of 99.7 % of the prescribed dose. Hot spots represented 0.3 % of the PTV. 6.2 %, 1.6 % and 0.3 % of the ipsilateral lung volume received 5 Gy (V5Gy), 10 Gy (V10Gy) and 20 Gy (V20Gy), respectively. Regarding the contralateral lung, V5Gy was 0.3 %, and V10Gy and V20Gy were nil. V5Gy accounted for 3.1 % of the heart. An average 580 monitor units were delivered. No acute or late grade ≥ 2 toxicities were observed. With a median follow-up of 26 months, no relapses occurred.CONCLUSION:In our study, VMAT allowed optimal dosimetry with consequential high therapeutic ratio in elderly and frail patients.

In the era of high-tech radiotherapy, hypofractionated schema is more and more widely used regardless of tumour sites. In this article, we expose the role, techniques and indications of hypofractionated radiotherapy in adjuvant breast radiotherapy.

Concomitant use of adjuvant tamoxifen (TAM) and radiation therapy (RT) is not widely accepted. We aim to assess whether this treatment is associated with an increased risk of developing subcutaneous fibrosis after conservative or radical surgery in breast cancer patients. We analysed 147 women with breast cancer treated with adjuvant RT, and who were included in the KFS 00539-9-1997/SKL 00778-2-1999 prospective study aimed at evaluating the predictive value of CD4 and CD8 T-lymphocyte apoptosis for the development of radiation-induced late effects. TAM (20 mg day(-1)) with concomitant RT was prescribed in 90 hormone receptor-positive patients. There was a statistically significant difference in terms of complication-relapse-free survival (CRFS) rates at 3 years, 48% (95% CI 37.2-57.6%) vs 66% (95% CI 49.9-78.6%) and complication-free survival (CFS) rates at 2 years, 51% (95% CI 40-61%) vs 80% (95% CI 67-89%) in the TAM and no-TAM groups, respectively. In each of these groups, the CRFS rates were significantly lower for patients with low levels of CD8 radiation-induced apoptosis, 20% (95% CI 10-31.9%), 66% (95% CI 51.1-77.6%), and 79% (95% CI 55-90.9%) for CD8/=16, 16-24, and24%, respectively. Similar results were observed for the CFS rates. The concomitant use of TAM with RT is significantly associated with an increased incidence of grade 2 or greater subcutaneous fibrosis; therefore, caution is needed for radiosensitive patients.

Resume L'hormonoradiotherapie (concomitante) est utilisee depuis plusieurs annees en pratique clinique quotidienne dans les cancers localement evolues de la prostate. Le transfert de ce concept en pathologie mammaire a ete tres peu rapporte dans la litterature mais semble pourtant licite devant l'hormono-dependance frequente des cancers du sein et la synergie potentielle de ces deux armes therapeutiques. En situation adjuvante, le tamoxifene est la molecule de reference du traitement antihormonal avec un avantage significatif, tant sur le taux de recidives locales que sur la survie globale. Les inhibiteurs de l'aromatase sont en cours d'evaluation dans cette indication et les premiers resultats sont prometteurs. In vitro, le tamoxifene ne semble pas avoir un effet cytoprotecteur vis-a-vis de la radiotherapie. En clinique, le peu d'essais publies confirment la superiorite de l'association concomitante de la radiotherapie et du tamoxifene par rapport a la radiotherapie seule en termes de taux de controle local apres chirurgie conservatrice. Avec l'association radiotherapie–tamoxifene, les donnees rapportees dans la litterature sont moins controversees pour la majoration de la fibrose pulmonaire que pour la fibrose sous-cutanee et son retentissement sur les resultats cosmetiques. L'association concomitante de la radiotherapie et des inhibiteurs de l'aromatase reste encore tres peu decrite dans la litterature. Le letrozole (Femara ® ) presente un effet radiosensibilisateur sur des lignees de cancer du sein transfectees par le gene de l'aromatase. Aucune donnee clinique concernant l'association radiotherapie–letrozole n'est actuellement disponible. Dans l'etude FEMTABIG ( Femara-Tamoxifen Breast International Group ), la sequence de la radiotherapie et du traitement hormonal etait libre (letrozole contre tamoxifene contre traitement sequentiel). L'etude ATAC ( Arimidex Tamoxifen Alone or in Combination ) a recemment demontre que l'anastrozole (Arimidex ® ) etait superieur au tamoxifene en situation adjuvante, mais elle ne renseigne pas sur le nombre de patients traites par l'association radiotherapie–anastrozole. Dans l'etude TEAM, comparant l'exemestane (Aromasine ® ) au tamoxifene, le traitement hormonal debutait obligatoirement apres la fin de la radiotherapie.

The use of intraoperative radiation therapy in breast cancer patients started about 20 years ago. Several retrospective and prospective studies have been published. Intraoperative radiation therapy was initially given as a boost to the tumour bed, followed by whole-breast irradiation. These studies have demonstrated the feasibility of the technique, with local control rates and cosmetic results similar to those obtained with standard treatments. Accelerated partial breast irradiation yields local recurrence rates as low as those observed after whole-breast irradiation. Intraoperative radiation therapy as a single irradiation modality with a unique dose has been investigated in recent prospective studies showing satisfactory local results. Intraoperative radiation therapy can be proposed either as a boost or as a unique treatment in selected cases (tumour size, nodal and hormonal status, patient's age). Intraoperative radiation therapy can be delivered by orthovoltage (50 kV) X-rays from mobile generators, or by electrons from linear accelerators, mobile or fixed, dedicated or not to intraoperative radiation therapy.

Patients with left-sided breast cancer are at risk of cardiac toxicity because of cardiac irradiation during radiotherapy with the conventional 3-dimensional conformal radiotherapy technique. In addition, many patients may receive chemotherapy prior to radiation, which may damage the myocardium and may increase the potential for late cardiac complications. New radiotherapy techniques such as intensity-modulated radiotherapy (IMRT) may decrease the risk of cardiac toxicity because of the steep dose gradient limiting the volume of the heart irradiated to a high dose. Image-guided radiotherapy (IGRT) is a new technique of IMRT delivery with daily imaging, which may further reduce excessive cardiac irradiation. Preliminary results of IGRT for cardiac sparing in patients with left-sided breast cancer are promising and need to be investigated in future prospective clinical studies.

One-day breast carcinoma treatment is defined as association of ambulatory surgery and intra-operative irradiation. Selection and rigorous process of patients is the key to success. The surgical technique is not changed by the radiotherapy. Patient's satisfaction index is very high. Financial loss should not be a hurdle to its implementation.

International audience

Treatment of glioblastoma multiforme (GBM) and brain metastasis remains a challenge because of the poor survival and the potential for brain damage following radiation. Despite concurrent chemotherapy and radiation dose escalation, local recurrence remains the predominant pattern of failure in GBM most likely secondary to repopulation of cancer stem cells. Even though radiotherapy is highly effective for local control of radio-resistant tumors such as melanoma and renal cell cancer, systemic disease progression is the cause of death in most patients with brain metastasis. Preservation of quality of life of cancer survivors is the main issue for patients with brain metastasis. Image-guided radiotherapy (IGRT) by virtue of precise radiation dose delivery may reduce treatment time of patients with GBM without excessive toxicity and potentially improve neurocognitive function with preservation of local control in patients with brain metastasis. Future prospective trials for primary brain tumors or brain metastasis should include IGRT to assess its efficacy to improve patient quality of life.

Background The ACCORD 16 phase II trial aimed to evaluate the objective response rate after combination of conventional chemoradiotherapy (CRT) and cetuximab in locally advanced anal canal carcinoma (LAACC). Patients and methods Immunocompetent patients with histologically confirmed LAACC received CRT [45 gray (Gy)] in 25 fractions over 5 weeks, fluorouracil and cisplatin during weeks 1 and 5), in combination with weekly dose of cetuximab (250 mg/m2 with a loading dose of 400 mg/m2 1 week before irradiation), and a standard dose boost (20 Gy). The trial was originally designed to include 81 patients to detect a 15% of objective response increase with the new combination in comparison with CRT. Results The trial was prematurely stopped after the declaration of 15 serious adverse events (SAEs) in 14 out of 16 patients. Five patients received the entire planned treatment, and the compliance was higher after amendments of the protocol. Among the 15 SAEs, 6 were unexpected. Grade (G) 3/4 acute toxic effects, observed in 88% patients, were general (n = 13, 81%), digestive (n = 9, 56%), dermatological (n = 5, 31%), infectious (n = 4, 25%), haematological (n = 3, 19%), and others (n = 9); and three patients suffered from six G3/4 late toxic effects. No treatment-related death was reported. All 11 assessable patients had an objective response consisting of six complete (55%) and five partial (45%) response 2 months after the end of the treatment. Thirteen patients were followed up with a median of 22 months [95% confidence interval (CI ): 18–27] and had a 1-year colostomy-free survival, progression-free and overall survival rate of 67% (95% CI: 40%–86%), 62% (95% CI: 36%–82%), and 92% (95% CI: 67%–99%), respectively. Conclusion CRT plus cetuximab was unacceptably toxic in this population of patients. Results of others phase II trials evaluating this combination are awaited to confirm these findings. Eudra CT No 2007-007029-38.

Background The Montpellier cancer institute phase II trial started in 2004 and evaluated the feasibility of intraoperative radiotherapy (IORT) technique given as a sole radiation treatment for patients with an excellent prognostic and very low recurrence risk. Methods Forty-two patients were included between 2004 and 2007. Inclusion criteria were patients ≥ 65 years old, T0-T1, N0, ductal invasive unifocal carcinoma, free-margin > 2 mm. IORT was delivered using dedicated linear accelerator. One fraction of 21 Gy was prescribed and specified at the 90% isodose using electrons. In vivo dosimetry was performed for all patients. Primary end-point was the quality index. Secondary endpoints were quality of life, local recurrences, cosmetic results, specific and overall survival. Results At inclusion, median age was 72 years (range, 66–80). Median tumor diameter was 10 mm. All patients received the total prescribed dose. No acute grade 3 toxicities were observed. Late cosmetic results were good at 5 years despite the poor agreement of accuracy assessment between patients and physicians. Four patients (9.5%) experienced a local failure and underwent salvage mastectomy. The 5 year-disease free survival is 92.7% (range 79.1−97.6). All patients are still alive with a median follow-up of 72 months (range 66–74). Conclusion Our results confirm with a long-term follow-up that exclusive partial breast IORT is feasible for early-breast cancer in selected patients. IORT provides good late cosmetics results and should be considered as a safe and very comfortable “one-step” treatment procedure. Nevertheless, patient assessments are essential for long-term quality results.