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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

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.

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

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.

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.

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.

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.

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.

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.

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.

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 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.

Purpose Ductal carcinoma in situ overall prognosis is excellent, but after breast conserving surgery, with or without radiotherapy, local recurrences can lead to locoregional or distant evolution and death. However, there are few data on optimal local recurrences treatment and long-term impact on survival. Patients and methods This study included 195 women treated from 1985 to 1996 by conservative surgery (CS) or conservative surgery followed by radiotherapy (CS + RT), presenting local recurrences, with a 156-month median follow-up. Results Eighty-two out of 195 (42%) local recurrences were non-invasive (in situ) and 113 (58%) invasive. In situ local recurrence was discovered by mammography in 80.5% of the cases versus 47.5% for invasive local recurrence (P = 0.0001). Salvage mastectomy was used in 53% of the cases after conservative surgery and 75% after conservative surgery followed by radiotherapy. The axillary nodal involvement rates were 11.8% and 25.8% among 17 and 62 patients with in situ and invasive local recurrences. Among 113 patients with invasive local recurrences and 82 with in situ local recurrences, 19 (16.8%) and three (3.6%) developed metastases, respectively. Among invasive local recurrences, comedocarcinoma subtype was highly predictive of subsequent metastases (32% versus 4.4%, P Conclusion Invasive local recurrence after ductal carcinoma in situ treatment could be a dramatic event, fully changing long-term prognosis. Early mammographic local recurrence diagnosis (if possible still at non-invasive stage) seems essential to avoid or minimize metastatic risk. Mastectomy remains the safest option but, in some cases, a new conservative approach could be discussed.

Background After breast conservative treatment (BCT), young age is a predictive factor for recurrence in patients with Ductal Carcinoma In Situ (DCIS) of the breast. The purpose of this study was to evaluate predictive factors for recurrence and outcomes in these younger women (under 40 years) treated for pure DCIS. Methods From 1974 to 2003, 207 cases were collected in 12 French Cancer Centers. Median age was 36.3 years and median follow-up 160 months. Seventy four (35.8%) underwent mastectomy, 67 (32.4%) lumpectomy alone and 66 (31.9%) lumpectomy plus radiotherapy. Results 37 recurrences occurred (17.8%): 14 (38%) were in situ and 23 (62%) invasive. After BCT, the overall rate of recurrence was 27% (33% in the lumpectomy plus radiotherapy group vs. 21% in the lumpectomy alone group). Comedocarcinoma subtype ( p = 0.004), histological size more than 10 mm ( p = 0.011), necrosis ( p = 0.022) and positive margin status ( p = 0.019) were statistically significant predictive factors for recurrence. The actuarial 15-year rates of local recurrence were 29%, 42% and 37% in the lumpectomy alone, lumpectomy and whole breast radiotherapy and lumpectomy + whole breast radiotherapy with additional boost groups respectively. After recurrence, the 10-year overall survival rate was 67.2%. Conclusion High recurrence rates (mainly invasive) after BCT in young women with DCIS are confirmed. BCT in this subgroup of patients is possible if clear and large margins are obtained, tumor size is under 11 mm and necrosis- and/or comedocarcinoma-free.

Summary Background We would like to assess the safety and effectiveness of prophylactic percutaneous endoscopic gastrostomy (PEG) tube feedings during concurrent chemoradiation for head and neck cancer. Methods Patients who underwent chemotherapy and radiation for head and neck malignancies were evaluated for their ability to resume oral feeding following treatment. All patients underwent PEG tube placement prior to the treatment because of the expected mucositis. Gastrostomy tubes were removed following treatment when the patients were able to resume oral feedings without aspiration. Results Between March 1999 and 2006, 104 patients with locally advanced head and neck cancer underwent concurrent chemotherapy and radiation. One patient declined placement of gastrostomy tube. Ninety patients (86%) developed grade 3–4 mucositis during chemoradiation. Five patients died during treatment from aspiration pneumonia and sepsis. One hundred two patients lost weight during treatment. The mean and median weight loss during concurrent therapy was, respectively, 8.5 and 8 kg (1–23.5 kg). Following treatment, tube feedings were continued 1–41 months (mean: 8 months; median: 5 months) because of continued weight loss, chronic dysphagia, or aspiration. At a median follow-up of 19 months (1–62 months), no patient developed serious complications from tube feedings. Conclusion Dysphagia resulting from the severe mucositis produced severe weight loss, despite tube feedings. Gastrostomy tube feedings are safe. Gastrostomy tubes should be placed prophylactically for patients undergoing chemoradiation for head and neck cancer.

Summary Purpose to analyse toxicity and response to a new scheme of neoadjuvant chemotherapy (CT) and concomitant radiochemotherapy (RT-CT) for locally advanced anal canal squamous-cell carcinoma (ACC). Patients and methods Eighty patients with an ACC > 40 mm and/or with lymph node involvement were included (1 T1, 52 T2, 14 T3, 13 T4, 18 No, 30 N1, 32 N2-N3). Two cycles of 5-fluorouracil (5-FU) and CDDP were delivered as neoadjuvant CT and two during RT-CT. Pelvic (± inguinal) RT delivered 45 Gy in 25 fractions of 1.8 Gy. Involved fields were boosted after a one to two month gap (15–20 Gy). The median follow-up was 29 months. Result One patient died of a pulmonary embolism on day 4. All patients received the entire treatment, with reduced 5-FU doses in 27% of the cases because of acute toxicity. Sixty-four grade 3 and five grade 4 toxicities were observed. No toxic death occurred. Complete response (CR) and partial response (PR) rates were, respectively, 10% and 51% after neoadjuvant CT, 67% and 28% after RT-CT and 93% and 5% after treatment completion (including 4 abdomino-perineal resections). The three-year actuarial overall, tumour-specific, colostomyfree, relapse-free, disease-free and event-free survivals were 86%, 88%, 73%, 70%, 67% and 63%, respectively. Conclusions Tolerance was good. After neoadjuvant CT, most of the patients were objective responders. After treatment completion, all but five achieved CR. The long-term results confirm the durability of local control and low toxicity on the sphincter. An ongoing phase III intergroup trial analyses the impact of neoadjuvant CT, and the benefit of a high-dose boost irradiation, on local control and colostomy-free survival.

Introduction Since the first breast cancer Intraoperative Radiation Therapy treatment in October 1992 performed in our institution, this technique never stopped to evolve. Until 2011 a linear accelerator delivering high energy electron beam was used to treat approximately 130 patients. The first treatments with INTRABEAM® system (Carl Zeiss SAS) using low energy X-rays were performed in October 2011. Materials and methods Nighty-four patients have now been treated with INTRABEAM®. For each, the radiation dose required was 20 Gy to the surface of the surgical margin in a single fraction. The Intrabeam® system produces low energy photons from a 50 kV and 40 μA source while preceding irradiation technique used electrons energy of 6 or 9 MeV. The isotropy of the low energy photon beam and the dose rate were measured before each treatment. Sterile applicators with variable diameters from 3 to 5 cm are selected to exactly fit the surgical cavity, thus allowing a homogeneous spherical irradiation. Results With INTRABEAM®, the dose attenuation is rapid (5 Gy at 1 cm from the applicator surface), thereby reducing damage to surrounding healthy tissue. The mobile X-ray source is installed in one of two operating ambulatory surgery and does not require as before the immobilization of a radiotherapy bunker. The time needed to deliver the dose was between 20 and 53 min and depends on the size of the applicator. The total time needed for the room and the staff for the dose delivery step is not more important with Intrabeam® system as before. Conclusion The shift from breast intraoperative radiotherapy using a linear accelerator to Intrabeam® was realized with no major problems in our institution. Using this new system has improved the workflow of radiotherapy and surgery, and thus increases the number of patients that can benefit from this technique.

4098 Background: The combination of radiotherapy and chemotherapy is a mainstay for anal cancer. Improving local control could avoid mutilating salvage. We evaluate the role of an intensified strat...

TPS131 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 1,950 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 fractio...

Purpose: Letrozole (LET) has recently been shown to be superior to tamoxifen for postmenopausal patients (pts). In addition, LET radiosensitizes breast cancer cells in vitro. We conducted a phase II randomized study to evaluate concurrent and sequential radiotherapy (RT)-LET in the adjuvant setting. We present here clinical results with a minimum follow-up of 24 months.Patients and Methods: Postmenopausal pts with early-stage breast cancer were randomized after conservative surgery to either: A) concurrent RT-LET (LET started 3 weeks before the first day of RT) or B) sequential RT-LET (LET started 3 weeks after the end of RT). Whole breast RT was delivered to a total dose of 50 Gy. A 10-16 Gy boost was allowed according to age and pathological prognostic factors. Pts were stratified by center, adjuvant chemotherapy, boost, and radiation-induced CD8 apoptosis (RILA). RILA was performed before RT as previously published (Ozsahin et al. Clin Cancer Res, 2005). An independent monitoring committee reviewed individual safety data. Skin toxicities were evaluated by two different clinicians at each medical visit (CTCAE v3.0). Lung CT-scan and functional pulmonary tests were performed regularly. DNA samples were screened for SNPs in candidate genes as recently published (Azria et al., Clin Cancer Res, 2008).Results: A total of 150 pts were randomized between 01/05 and 02/07. Median follow-up is 26 months (range, 3-40 months). No statistical differences were identified between the two arms in terms of mean age; initial TNM; median surgical bed volume; post surgical breast volume. Chemotherapy and RT boost were delivered in 19% and 38% of pts, respectively. Nodes received 50 Gy in 23% of patients without differences between both arms. During RT and within the first 6 weeks after RT, 10 patients (6.7%) presented grade 3 acute skin dermatitis during RT but no differences were observed between both arms (4 and 6 patients in arm A and B, respectively). At 26 month of follow-up, grade 2 and more radiation-induced subcutaneous fibrosis (RISCF) was present in 4 patients (3%) without any difference between arm A (n = 2) and B (n = 2), p=0.93. In both arms, all patients that presented a RICSF had a RILA lower than 16%. Sensitivity and specificity were 100% and 39%, respectively.No acute lung toxicities were observed and quality of life was good to excellent for all patients.SNPs analyses are still on-going (Pr Rosenstein, NY).Conclusion: Acute and early late grade ≥ 2 dermatitis were similar in both arms. The only factor that influenced RISCF was a low radiation-induced lymphocyte apoptosis yield. We confirmed prospectively the capacity of RILA for identifying hypersensitive patients to radiation. Indeed, patients with RILA superior to 16% did not present late effects to radiation and confirmed the first prospective trial we published in 2005 (Ozsahin et al., Clin Cancer Res). Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 956.

Background:The impact of postmastectomy radiotherapy (PMRT) on survival has been controversial for decade in intermediate-risk patients.We present here our monocentric long-term carcinologic and quality of life results in the subset of patients classified at intermediate risk and treated with PMRT.Material and Methods: From 1990 to 2000, 1622 patients received adjuvant radiotherapy after mastectomy. Among them, 421 were defined at intermediate risk of local recurrence i.e. (i) one to 3 positive nodes (ii) negative node but younger than 35 years old and/or pT3-T4 and/or grade 3 and/or invasive multifocality and/or lymphovascular invasion. PMRT consisted in a 50 Gy-electron therapy to the chest wall with node irradiation if indicated. Adjuvant chemotherapy and/or hormonotherapy were administered according to our local guideline. Patients were visited every 6 months for at least 10 years. Quality of life questionnaires (EORTC QLQC30/BR23) were filled in at the last medical visit.Results: Median age was 57 years (range, 27-80). One-hundred thirty five patients (32%) and 286 (68%) were premenopausal and menopausal, respectively. Seventy-five percent of the patients presented a ductal invasive carcinoma and 55% one to three positive axillary nodes. The median number of nodes was 13 (range, 3-27). 77% of the patients presented an axillary dissection with more than 10 nodes. 32% of the nodes were associated with capsular effraction. In the node negative subgroups, grade 3, lymphovascular invasion, multifocality, pT3-4, and age < 35 were found in 57%, 19%, 33%, and 4%, respectively. Extensive DCIS was found in 227 patients (54%). Hormonal receptors (ER and/or PR) were positive in 321 patients (76%) and therefore treated with postoperative tamoxifen for 5 years. Adjuvant chemotherapy was delivered in 126 patients and mainly included anthracyclin. HER2 status was not available at that time in our center. Chest wall RT was delivered in all patients to a median total dose of 50 Gy (range, 43-62). Sus-clavicular and internal mammary chain were irradiated in 294 and 346 patients, respectively. With a 10-y median follow-up, 12 (2.8%) and 74 (17.6%) patients presented locoregional and metastatic recurrences, respectively. Locoregional-free survival (LRFS) was 98.3% and 97.1% at 5 and 10 years, respectively. None of the 12 patients presented metastasis before local recurrence. Multifactorial analysis showed a significant impact of LRFS on metastatic-free survival (p Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4112.

Abstract #6153 Background Breast cancer (BC) is the most frequent second malignancy in women treated for Hodgkin's disease (HD), but there are few specific data on these tumors. This study assesses histopathological features, locoregional and systemic treatments as well as prognostic factors of these secondary BC. Material and methods: 127 women treated for HD in 9 centers subsequently developed 143 BC. Median age at HD diagnosis was 25 years. HD stages were I, II, III and IV in 28%, 49%, 16% and 7%. Radiotherapy (RT) alone was used in 44 cases and chemotherapy (CT) + RT in 83 cases. Twelve patients relapsed and had a new treatment by RT (3), CT (5) or both (4). Results: First BC occurred after 18-year median interval (20 years: 40%). TNM classification (126/143) showed 23 mammographically detected T0 (18%), 54 T1 (43%, 40 T2 (32%) and 9 T3T4 (7%). 129 tumors were infiltrating carcinoma (IC) and 14 (10%) DCIS. Twenty-four (17%) tumors were multifocal. Five patients had metastasis at diagnosis; 135 tumors were operated (121 IC and 14 DCIS): 57 (42%) by conservative surgery (40 with RT) and 78 (58%) by mastectomy (5 with RT). Axillary dissection (AD) and SNB were performed in 74% and 23% of the cases. Median tumor size for IC was 19 mm. Axillary nodal involvement (ANI) was found in 28% of IC (pN1-3 : 22%; pN>3 : 6%). ER and PgR were positive in 57% and 49%. 43 (39%) tumors were SBR III (high grade). Chemotherapy (CT) and hormonotherapy (HT) were performed in 47% and 42% of IC. With a 5-year median FU, 17 patients (12%) developed local recurrences (LR) and 35 (30%) had metastases. Significant metastasis predictive factors were ANI and SBR III; 12 (10%) women developed a third cancer. 5 and 10-year overall survival (OS) rates were 69% and 53%, and disease-specific survival (DSS) rates 72% and 62%. 5-year DSS rates were 79% for T0T1 versus 44% for pT2T3T4 (p=0.0068) and 81% for pN0 versus 65% for pN+ (p=0.0012). Conclusion Young women (especially 15-25 years) treated for HD should be carefully monitored by mammography, ultrasound and maybe MRI in order to detect early occurrence of BC. The prognosis of small lesions (pTis/pT1) is excellent and conservative treatment often feasible. This study is still ongoing, with 200 planned cases. Optimal adjuvant treatment options will be discussed and compared with a former series including 133 cases (Radiotherapy and Oncology, 2001, 59: 247-255). Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6153.