[Radiotherapy and targeted therapy for the management of breast cancer: A review]. / Radiothérapie et thérapie ciblée pour la prise en charge du cancer du sein : mise au point.

The purpose of this study was to review the current knowledge regarding combinations of the most commonly used targeted therapies or those under development for the management of breast cancer with radiation therapy. Several studies have shown that the combination of radiation therapy and tamoxifen increased the risk of radiation-induced lung toxicity; therefore, the two modalities are generally not given concurrently. The combination of HER2 inhibitors (trastuzumab, pertuzumab) and radiation therapy appeared to be safe. However, trastuzumab emtansine (T-DM1) should not be given concomitantly with brain radiation therapy because this combination may increase the risk of brain radionecrosis. The combination of radiation therapy with other new targeted therapies such as new selective estrogen receptor modulators (SERDs), lapatinib, cell cycle inhibitors, immune checkpoint inhibitors, or molecules acting on DNA damage repair seems feasible but has been mainly evaluated on retrospective or prospective studies with small numbers of patients. Moreover, there is a great heterogeneity between these studies regarding the dose and fractionation used in radiotherapy, the dosage of systemic treatments and the sequence of treatments used. Therefore, the combination of these new molecules with radiotherapy should be proposed sparingly, under close monitoring, pending the ongoing prospective studies cited in this review.

Long-term efficacy and tolerance of a technique for postmastectomy electron beam radiation therapy of the unreconstructed chest wall and lymph node areas for non-metastatic breast cancers.

PURPOSE: To evaluate the long-term tolerance and outcome of patients irradiated with an electron beam technique used since 2007 on the chest wall and lymph node areas after mastectomy for non-metastatic locally advanced breast carcinoma. PATIENTS AND METHODS: All patients irradiated with an improved electron beam technique after mastectomy for non-metastatic breast carcinoma between 2007 and 2011 at Institut Curie (France) were included in this descriptive study. The technique has already been described in other studies, as has its 5-year tolerance and non-inferiority compared to photon irradiation. Acute and chronic toxicity were collected using CTCAE v 3.0. A clinical examination was carried out each week during the radiotherapy and at each 6 months consultation with one mammogram per year at the Institut Curie for at least 5 years. The patients then continued to be followed either at the Institut Curie or in private practice with a good transmission of outpatient consultations, thanks to a system of forms to be completed and integrated into the electronic files. Quantitative and qualitative data are defined by mean and proportion. Statistical comparisons were made by computer using the Chi2 test and Fisher's exact test for categorical variables. Recurrence-free survival was defined as the time between the end of treatment and the date of recurrence or death. Overall survival was defined in the same way without taking into account recurrences. Patients who did not report any events were censored at the date of last news. RESULTS: Of the 796 patients included, 51.3% had multifocal lesions, 10.1% had triple negative status, and 18.8% displayed overexpression of the Her2 receptor, 196 (24.6%) patients received neoadjuvant chemotherapy and 208 (26.1%) systemic treatment during radiotherapy (chemotherapy or targeted therapy); 514 (64.6%) had at least one positive lymph node. The internal mammary chain (IMC) was irradiated in 85.6% of cases, the supraclavicular areas in 88.3% of cases, the infraclavicular in 77.9% of cases and the axillary area in 14.9% of cases. With a median follow-up of 113 months (range: 2-164 months), locoregional recurrence-free survival and overall 10-year survival was respectively 94.02%, (95% CI: 92.13-98.94) and 79.84% (95% CI: 76.83-82.97). Median survival was not reached. In the long term, 29.6% of patients had telangiectasias (grade 1: 23.3%, grade 2: 5.2%, grade 3: 1.1%). There were 279 patients (35.1%) with secondary breast reconstruction on average 21 months after all treatments. IMC irradiation was not associated with a majority of pulmonary toxicity. Thirty-five patients developed chronic heart disease after radiotherapy, 30 of whom had received anthracyclines and 9 had received traztuzumab. Three of these reported a coronary ischaemic event, including 2 irradiated on the left and 1 on the right, the 4 were irradiated in the vicinity of the IMC and the other lymph node areas, but presented many other cardiovascular risk factors (between 2 and 4). During follow-up, 4.9% of patients had a contralateral recurrence (n=39) and 5.5% had a second non-breast cancer (n=44), of the 6 bronchopulmonary cancers diagnosed, none appeared to be related to chest wall radiotherapy. CONCLUSION: This study confirms that the improved postmastectomy electron beam radiation therapy technique is well-tolerated after nearly 10 years of follow-up.

Late hepatic toxicity after breast cancer intensity-modulated radiotherapy using helicoidal tomotherapy.

PURPOSE: Helical tomotherapy (HT) is a rotational intensity-modulated radiation therapy (IMRT) technique that allows target conformal irradiation and efficient organs at risk (OAR) sparing in the case of complex target volumes and specific anatomic considerations, but increases the "low-dose bath" to non-target volumes. The aim of this study was to analyze the delayed hepatotoxicity after rotational IMRT (HT) radiation therapy for non-metastatic breast cancer. PATIENTS AND METHODS: This single-center retrospective study included all non-metastatic breast cancer patients with a normal pre-radiotherapy biological hepatic function who were treated with tomotherapy between January 2010 and January 2021 and for whom the dosimetric parameters for the whole liver were assessable. A logistic regression analysis was employed. The selected covariates for the multivariate analysis were those with a P-value that was less or equal to 0.20 in the univariate analysis. RESULTS: Forty-nine patients were included in this study: 11 patients (22%) received Trastuzumab for 1 year in tumors with an HER2-expression; 27 patients (55%) received radiation therapy for cancer of the right or bilateral breasts; 43 patients (88%) received lymph node irradiation and 41 patients (84%) received a tumor bed boost. Mean and maximum doses to the liver were 2.8Gy [0.3-16.6] and 26.9Gy [0.7-51.7], respectively. With a median follow-up after irradiation was 5.4 years (range, 6 to 115 months), 11 patients (22%) had developed delayed low grade biological hepatic abnormalities: all patients had grade 1 delayed hepatotoxicity; 3 patients (6%) had additional grade 2 delayed hepatotoxicity. There was no hepatotoxicity at grade 3 or higher. According to the univariate and multivariate analysis, Trastuzumab was a significant predictive variable of late biological hepatotoxicity (OR=4.4 [1.01-20.18], P=0.04). No other variable was statistically associated with delayed biological hepatotoxicity. CONCLUSION: Delayed hepatotoxicity after multimodal non-metastatic breast cancer management including rotational IMRT was negligible. Consequently, the liver doesn't have to be considered like an organ-at-risk in the analysis of breast cancer radiotherapy but future prospectives studies are needed to confirm these findings.

[Biological, preclinical and clinical aspects of the association between radiation therapy and CDK4/6 inhibitors]. / Aspects biologiques, précliniques et cliniques de l'association de radiothérapie et d'inhibiteur de CDK 4/6.

Several clinical studies have shown that CDK4/6 inhibitors (CDK4/6i) improve survival in patients with metastatic or locally advanced HR-positive, HER-2-negative breast cancer (BC). The aim of this review was to synthesize the biological, preclinical and clinical aspects of the treatment of BC with CDK4/6i, with a focus on the combination of CDK4/6i and radiotherapy. The DNA damage induced after exposure of cells to ionizing radiation activates control pathways that inhibit cell progression in the G1 and G2 phases and induce a transient delay in progression in the S phase. These checkpoints are in particular mediated by cyclin-dependent kinases (CDK) 4/6 activated by cyclin D1. Several preclinical studies have shown that CDK4/6i could be used as radiosensitizers in non-small cell lung cancer, medulloblastoma, brainstem glioma and breast cancer. CDK4/6 inhibition also protected against radiation-induced intestinal toxicities by inducing redistribution of quiescent intestinal progenitor cells, making them less radiosensitive. Clinical data on the combination of CDK inhibitors and radiotherapy for both locoregional and metastatic irradiation are based on retrospective data. Nevertheless, the most optimal therapeutic sequence would be radiotherapy followed by palbociclib. Pending prospective clinical trials, the concomitant combination of the two treatments should be done under close supervision.

Multidisciplinary management and role of reirradiation in the treatment of a breast cancer patient with four locoregional recurrences.

Breast cancer is a frequent and sometimes fatal disease. The risk of locoregional recurrence has considerably decreased since the introduction of adjuvant treatments (radiotherapy, chemotherapy, hormone therapy). Nevertheless, some patients present a risk of multiple local recurrences. We report here the case of a patient who had four locoregional breast cancer recurrences. There is currently no validated biomarker that allows the prediction of recurrence. Salvage surgery, most often mastectomy, remains the recommended treatment for the management of these recurrences in the irradiated field. However, increasingly, depending on the patient's wishes and the technical possibilities of multiple surgeries, the question of a second conservative treatment and reirradiation arises. This type of management must in all cases be multidisciplinary and in specialized centers. Reirradiation must in any case try to give maximum priority to the protection of healthy tissue already irradiated.

Long-term follow-up results of intensity-modulated radiotherapy with helicoïdal tomotherapy for non-metastatic breast cancers: Single centre experience.

PURPOSE: Intensity-modulated radiotherapy with helical Tomotherapy is a novel radiation therapy technique, which may be beneficial in several features compared to traditional methods. Our aim was to evaluate the local control, overall survival, progression free survival and adverse events in breast cancer patients treated with this new technique. MATERIAL AND METHODS: This is retrospective analysis of patients irradiated with intensity-modulated radiotherapy with helical Tomotherapy. Overall survival and progression free survival curves were plotted with Kaplan-Meier method. We also analysed the overall survival and progression-free survival data by molecular subgroups. Long-term toxicity including skin, cardiac and pulmonary complications were also evaluated. Multivariant logistic regression analysis was performed to determine the predictors of the side effects. RESULTS: Between 2009-2015, 179 consecutive patients with 194 treated breasts were irradiated with intensity-modulated radiotherapy with helical Tomotherapy. The median follow-up were 65 months. The overall survival rate was 89.2% (95% confidence interval [95CI]: 83.5-95.4%), while disease-free survival rate was 85.4% (95CI: 80.2-91%). The Human epidermal growth factor receptor 2-positive patients had the best 5-year overall survival data of 95% (95CI: 85.9-100%). Long-term skin toxicity was the most common, seen in a total of 20.7% of the patients. CONCLUSION: Intensity-modulated radiotherapy with helical Tomotherapy could be safely used for adjuvant breast cancer irradiation in patients with complex anatomy and provides favourable long-term prognosis with acceptable late toxicity.

Can we treat with radiation breast cancer patients with covid-19 infection? Results from a prospective study.

PURPOSE: The coronavirus disease 2019 (covid-19) caused by the severe acute respiratory syndrome coronavirus 2 (Sars-Cov-2) is at the origin of a global pandemic. This pandemic has prompted the current health system to reorganize and rethink the care offered by health establishments. We report the early and late toxicity in patients infected with covid-19 treated at the same time for early-stage breast cancer. MATERIAL AND METHODS: This is a monocentric prospective study of patients treated in our hospital between March and June 2020 who were diagnosed with covid-19 infection. The inclusion criteria were to be irradiated for early-stage breast cancer and to have a positive covid diagnosis on a polymerase chain reaction (PCR) test and/or a lung computed tomography (CT) scan and/or suggestive clinical symptoms. All of them needed 6 months follow-up clinic after the end of the radiotherapy with clinical examination, mammogram, as well as CT scan to evaluate the lung status. Radiotherapy consisted of breast or chest wall irradiation with or without lymph node irradiation, with protocols adapted to pandemic situation. The treatment-related toxicity was graded according to the Common Toxicology Criteria for Adverse Events (version 4.03). RESULTS: All 350 patients treated for early-stage breast cancer were studied. Of them, 16 presented clinical symptoms of covid-19 infection, and of them 12 had clinical, CT scan and PCR confirmation. This entire cohort of 12 patients with median age of 56years (range: 42-72 years) underwent their radiotherapy. During the radiotherapy, nine patients presented radiodermatitis: eight grade 1 (66%) and one grade 2 (8%). Two patients with lymph nodes irradiation presented grade 2 oesophagitis. Late toxicity was evaluated 6 months after the end of the radiotherapy, and there was no radiation or covid lung sequel on the CT scans. One patient presented covid-related dyspnoea, and two had fibrosis. CONCLUSION: The half-year follow-up of prospective covid-19 cohort, treated for early-stage breast cancer demonstrated an acceptable toxicity profile with few low-grade adverse events. It seems that the covid-19 infection does not appear to increase the side effects of radiotherapy. Therefore radiotherapy should not be delayed.

Unusual severe radiation-induced toxicity in a patient with discoid lupus erythematosus: A case report and critical review of the literature.

Data on the incidence and severity of radiation-induced toxicity in patients with systemic and/or cutaneous lupus erythematosus (SLE/CLE) are very limited. After reporting the case of a patient who experienced major toxicity and CLE flare in the irradiated area following breast irradiation, we conducted a comprehensive literature review of available data in this setting. The few retrospectives studies which have evaluated both the risk of toxicity in SLE/CLE patients and/or the potential induction or reactivation of SLE/CLE with radiotherapy have not shown differences between SLE/CLE patients and controls. Several other factors such as concurrent chemotherapy, a particular genetic background, or lupus treatments (essentially hydroxychloroquine) can explain severe radiation-induced toxicity. Therefore, patients with SLE/CLE should be irradiated like patients without SLE/CLE, with close monitoring during radiotherapy if other risk factors exist. Further studies examining a larger number of patients would probably allow a better understanding of the radiosensitivity of these patients.

[Patient selection and early tolerance of whole breast irradiation according to the "Fast Forward" protocol: Preliminary results]. / Sélection de patientes et tolérance précoce de l'irradiation mammaire selon le protocole « Fast Forward ¼ : résultats préliminaires.

PURPOSE: Moderate hypofractionated radiotherapy has become routine practice for a selected population of patients treated for early-stage breast cancer. In April 2020, the Fast Forward (FF) study was published which introduced another extreme hypofractionated radiotherapy regimen in five sessions over a week. The aim of this work is to evaluate the population of first patients in whom this regimen was used in our department, as well as the results in terms of early toxicity. MATERIAL AND METHODS: We retrospectively analysed all the patients treated in our department according to the Fast Forward protocol after establishing an institutional consensus regarding the selection of patients with breast cancer without indication for lymph node irradiation. All patients received breast-only irradiation at a total dose of 26Gy in five fractions according to protocol. All patients were treated by modern conformational techniques with planning large volume coverage between 95 and 100%. Acute toxicity of the treatment was assessed using the NCI CTC v4.0 scale and the general condition was assessed according to the WHO classification. RESULTS: Between August 2020 and May 2021, 30 patients were included, treated on the breast alone without complement on the tumour bed or irradiation of the lymph node areas. The median age of the patients was 80years (range: 60-85years) with performance status 2 in 27 cases (89%). Only one patient had metastatic disease (3%), one patient presented locally advanced and 28 (94%) patients had early stage disease. Three patients (10%) were treated in dorsal decubitus according to the "field in the field" technique and 27 patients (90%) in isocentric lateral decubitus, which made it possible to avoid the organs at risk such as the heart (average dose of less than 1Gy) and the lungs. The early toxicity observed was grade I radio dermatitis in 8 patients (27%). No grade 2 and 3 toxicity, as well as radiation-induced pain or lymphedema were observed. CONCLUSIONS: The results of this series of patients treated with hypofractionated radiotherapy according to the Fast Forward protocol on the breast alone with adapted techniques show that the protocol is feasible, with little early toxicity but a greater follow-up is necessary to assess long-term toxicity.

Radiotherapy of breast cancer.

Adjuvant radiotherapy is an essential component of the treatment of breast cancer. After conservative surgery for an infiltrating carcinoma, radiotherapy must be systematically performed, regardless of the characteristics of the disease, because it decreases the rate of local recurrence and by this way, specific mortality. A boost dose over the tumour bed is required if the patient is younger than 50 years-old. Partial breast irradiation could be routinely proposed as an alternative to whole breast irradiation, but only in selected and informed patients. For ductal carcinoma in situ, adjuvant radiotherapy must be also systematically performed after lumpectomy. After mastectomy, chest wall irradiation is required for pT3-T4 tumours and if there is an axillary nodal involvement, whatever the number of involved lymph nodes. After neoadjuvant chemotherapy and mastectomy, in case of pN0 disease, chest wall irradiation is recommended if there is a clinically or radiologically T3-T4 or node positive disease before chemotherapy. Axillary irradiation is recommended only if there is no axillary surgical dissection and a positive sentinel lymph node. Supra- and infraclavicular irradiation is advised in case of positive axillary nodes. Internal mammary irradiation must be discussed case by case, according to the benefit/risk ratio (cardiac toxicity). Hypofractionation regimens (42.5Gy in 16 fractions, or 41,6Gy en 13 or 40Gy en 15) are equivalent to conventional irradiation and must prescribe after tumorectomy in selected patients. Delineation of the breast, the chest wall and the nodal areas are based on clinical and radiological evaluations. 3D-conformal irradiation is the recommended technique, intensity-modulated radiotherapy must be proposed only in specific clinical situations. Respiratory gating could be useful to decrease the cardiac dose. Concomitant administration of chemotherapy in unadvised, but hormonal treatment could be start with or after radiotherapy.

Radiotherapy and pregnancy.

We present the updated recommendations of the French society for radiation oncology on radiotherapy and pregnancy. The occurrence of cancer during pregnancy is a rare event (approximately 1 in 1000 pregnancies). The risks for the embryo or the foetus depend on the gestational age at the time of irradiation. The main risks are malformations with microcephaly and mental retardation. There is also a risk of radiation-induced cancer in the unborn child. In the case of only supradiaphragmatic irradiation, radiotherapy can be performed most often in pregnant women without risk to the foetus. On the other hand, in the case of an indication for subdiaphragmatic irradiation, therapeutic termination of the pregnancy should be proposed. In all cases, when radiotherapy is chosen, a phantom estimation of the dose delivered to the foetus, confirmed by in vivo measurement, is recommended. Conformational radiotherapy is the preferred technique because of the lower dose delivered to the foetus (except in tumour locations where other techniques such as IMRT are recommended).

Clinical practice of breast cancer protontherapy: A single-centre experience from selection to treatment.

PURPOSE: Breast protontherapy efficiently limits cardiac, lung and contralateral breast exposure, which may clinically translate into better late tolerance profile compared with classic photon techniques. While breast protontherapy is already implemented in the United States and in some European countries, clinical experience of breast cancer protontherapy is currently limited in France. The aim of this study is to evaluate the clinical practice of breast cancer protontherapy at the Institut Curie in order to implement this technique at a larger scale. MATERIALS AND METHODS: Data from all breast cancer patients that have been addressed to the protontherapy centre of Orsay (CPO, Institut Curie) for adjuvant breast protontherapy were retrieved. We analysed why these patients were ultimately treated with protontherapy or not. RESULTS: Between November 2019 and November 2020, eleven breast cancer patients have been evaluated for adjuvant protontherapy at the CPO. Two of them were ultimately treated with proton beams; adjuvant breast protontherapy therapy was well tolerated. The nine other patients were not treated with protontherapy due to lack of availability of protontherapy treatment rooms in acceptable time limits, at the time of patient evaluation. CONCLUSION: Despite dosimetric advantages and excellent clinical tolerance, lack of availability of protontherapy machines currently limits wider implementation of breast protontherapy.

[Concurrent radiation therapy and dual HER2 blockade in breast cancer: Assessment of toxicity]. / Association du double blocage de HER2 et radiothérapie dans la prise en charge du cancer du sein exprimant HER2.

PURPOSE: The tolerance of the concurrent use of radiotherapy, pertuzumab and trastuzumab is unknown. The purpose of this study was to evaluate the toxicity of this association in patients treated for HER2 positive metastatic and/or locally recurrent unrespectable breast cancer. MATERIAL AND METHODS: A retrospective study was performed in our institution for all consecutive patients treated with concurrent irradiation, pertuzumab and trastuzumab. The radiotherapy was performed while pertuzumab and trastuzumab were administrated as a maintenance treatment at the dose of 420mg (total dose) and 6mg/kg respectively every 3 weeks without chemotherapy. Toxicity was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Left ventricular ejection fraction (LVEF) was measured at baseline and then every 3-4 months. RESULTS: We studied 77 patients. treated in between 2013 and 2019 with median follow-up of 38 months (range 0-264 months). Median age was 53 years (33-86). There were 50 patients (64.9%) with metastatic and 27 patients (35.1%) with recurrent disease. All patients received docetaxel followed by P-T as first line treatment and they received 34 cycles (10-85) of pertuzumab and trastuzumab. All patients experienced partial or complete response according to RECIST criteria. Irradiation volumes were whole breast (41 patients, 53.2%) and chest wall (29 patients, 37.7%) at a dose of 50Gy with a median duration of 39 days. Radiotherapy of lymph nodes was performed in 53 patients (68.8%) as following: supraclavicular-infraclavicular and axillary lymph nodes in 52 patients (67.5%), and internal mammary nodes in 31 patients (40.3%). For 20 patients. (26.0%) radiotherapy was palliative: bone irradiation (12 patients, 15.6%), whole-brain radiotherapy (2 patients, 2.6%), cerebral metastasis irradiation (6 patients). As early toxicity we observed: radio dermatitis as following: 36 patients (46.8%) presented grade I, 17 patients (22.1%) presented grade II, and 3 patients (3.9%) presented grade III. One patient (1.3%) presented grade II esophagitis. One patient (1.3%) presented asymptomatic decrease of LVEF during treatment and 6 patients (7.7%) presented a decrease of LVEF. There was no radiation-induced pneumonitis. As late toxicity, we observed 1 (1.3%) case of grade I and 1 (1.3%) with grade II telangiectasia. There was 1 case (1.3%) of grade III cardiac toxicity, 8 months after the concurrent treatment. CONCLUSION: The concurrent use of radiotherapy, pertuzumab and trastuzumab is feasible with good tolerance. Larger prospective data with longer follow-up is needed to confirm these results.

Cardiac radiation-induced sarcomas: A SEER population-based study and a literature review.

PURPOSE: The aim of this study was to better understand the incidence and the clinical characteristics of cardiac radiation-induced sarcomas (RIS). MATERIAL AND METHODS: We used the surveillance, epidemiology, and end results (SEER) program cancer registry data, the largest cancer database in the United States in order to identify all cardiac RIS between 1973 and 2015. We relied on the Memorial Sloan-Kettering Cancer Center (MSKCC)-modified 1948 Cahan criterions for RIS identification. RESULTS: Out of 8,136,951 cancer patients from the SEER database, we identified 448 patients diagnosed with cardiac sarcomas. Of these 448 cardiac sarcoma patients, two were considered to have developed a cardiac RIS: a metastatic rhabdomyosarcoma occurring after one to two years following lung carcinoma irradiation, and a soft tissue sarcoma (of unspecified type) developed six years after radiation therapy for an aggressive left-sided breast carcinoma. Based on this observation, we estimated that cardiac RIS represented about 0.4% (95% CI 0.1%-1.6%) of all cardiac sarcomas. A literature review has been conducted and yielded three additional cases of cardiac RIS. CONCLUSION: Cardiac RIS are extremely rare malignancies, associated with a very pejorative prognosis. The two reported histologies are angiosarcomas and rhabdomyosarcomas, which might be over-represented among cardiac RIS. A metastatic evolution is possible for cardiac radiation-induced rhabdomyosarcomas. Surgical excision, when feasible, is a therapeutic option and is the only specific treatment reported to this date.

Dosimetric comparison of four high performance techniques for irradiation of breast cancer patients.

PURPOSE: The use of IMRT for the treatment of breast cancer has been growing considerably in our institution since 2009. Alternatively, helical tomotherapy (HT) using a field width of 2.5 and 5cm (HT_FW_5), volumetric-modulated arc therapy (VMAT), or proton therapy with pencil-beam scanning (PT-PBS) have also been used to reduce treatment duration or optimize organ-at-risk (OAR) sparing. The purpose of this study was to compare the 4 treatment modalities available at our site. PATIENTS AND METHODS: We studied 10 patients treated for breast cancer with lymph node involvement. The prescribed dose was 51.8Gy to the breast with a simultaneous integrated boost up to 63Gy, and 50.4Gy to lymph nodes in 28 fractions. The CTV was delineated according to ESTRO Guidelines. Dosimetric planning in routine clinical practice was performed using HT_FW_2.5. The approved clinical plan was compared to the 3 other plans. Dosimetric goals for PTV coverage were D95%≥95% and D2%≤107% of the prescribed dose. Mean and maximum doses to OAR were recorded. RESULTS: HT_FW_5 and VMAT plans ensure equivalent or even better PTV coverage compared to the initial clinically approved plan but at the cost of poorer OAR sparing. PT_PBS plans showed that an excellent PTV coverage can be maintained with significantly lower doses to OAR. CONCLUSION: HT_FW_5 and VMAT plans allow a significant reduction of treatment duration and can be a good alternative to HT_FW_2.5 for specific populations. HT_FW_2.5 could be chosen for patients at higher risk of side effects. In addition, PT_PBS should be considered in the near future as it has been shown to have a major potential benefit to lower the risk of side effects with the same level of PTV coverage.

Evaluation of a software for automatic delineation of the mammary gland and organs at risk in patients treated for breast cancer in lateral position.

PURPOSE OF THE STUDY: The purpose of this study was to assess the potential for improvement of routine breast and organs at risk contouring in patients treated in the lateral decubitus position using Workflow Box™ (Mirada Medical™, UK) automatic contouring software. MATERIALS AND METHODS: Automatic contouring of the breast by this software is currently based on an atlas created from isodoses representing 95% of the prescribed dose in a population of patients previously treated at institut Curie. Forty cases of breast cancer (20 right breasts and 20 left breasts) were contoured by three radiation oncologists specialized in breast cancer, allowing the creation of a new atlas in the automatic contouring software. This study assessed the quality of contouring in 20 patients (ten right breasts and ten left breasts) by comparing manual contouring performed by the expert radiation oncologists (reference) with those generated by the old and new atlases developed at Institut Curie. The accuracy of contouring was assessed by overlap volume and the associated standard deviations. RESULTS: Breast contouring based on the new atlas and by radiation oncologists presented a mean overlap of 0.80±0.09 for the right breast and 0.81±0.06 for the left breast. By comparing volumes of interest contoured by radiation oncologists and those obtained from the old atlas, mean overlap volumes were 0.75±0.08 and 0.74±0.13 for the right and left breasts, respectively. Twenty cases (ten right breasts and ten left breasts) used to create the new atlas were also reprocessed by this same atlas in order to assess the quality of automatic contouring of the breast when the case was already known to the software. The mean overlap volume in this case was 0.84±0.08 for the right breast and 0.83±0.06 for the left breast. Finally, after automatic contouring of organs at risk by means of the new atlas, the mean overlap volume was 0.87±0.04 for the heart and 0.93 for each lung (±0.05 for the right lung and±0.04 for the left lung). CONCLUSION: Workflow Box™ automatic contouring software, based on our new atlas provides reliable and clinically relevant organs at risk and breast contouring. The contours proposed by the software from the new atlas were better than those obtained with the previous atlas based on 95% isodoses obtained from old treatment plans. This software has therefore become more efficient, justifying its use in routine clinical practice for breast cancer contouring in patients treated in the lateral decubitus position. Investigations are currently underway to develop a fully automated process to ensure reliable, robust and operator-independent contouring and breast cancer treatment dosimetry in the lateral decubitus position. Promising preliminary results have already been obtained.

Institut Curie guidelines on breast target volume delineation for patients treated in lateral position.

PURPOSE: To develop guidelines for and describe the delineation of breast for patients treated in lateral position and to transform this three-dimensional technique based on the virtual simulation to volume-based modern intensity-modulated irradiation technique. MATERIAL AND METHODS: In our department, during the daily delineation, radiation oncologists specialized in breast cancer treatment sought consensus on the delineation of clinical treatment volume of the breast through dialogue based on cases. A radiation oncologist delineated clinical treatment volumes on CT scans of five to 20 patients, followed by a discussion and adaptation of the delineation between all radiation oncologists of the team. The consensus established between clinicians was discussed, corrected and improved. All patients were delineated in treatment position; skin markers were used to visualize the breast tissue after careful palpation. RESULTS: Breast clinical treatment volume was situated and delineated between pectoral muscle and 5mm below the skin (dosimetric considerations), within the space outlined by skin markers, that showed the limits of the palpable breast tissue. In lateral position some vessels were very useful to define the limits as rami mammarii (from thoracica interna) for the internal one and thoracica lateralis for the external. This is the first atlas proposed for the delineation of the breast clinical treatment volumes for breast cancer using alternative technique of breast irradiation (lateral). CONCLUSION: This atlas will be helpful for the volume definition in our daily practice of breast irradiation in lateral position and can open perspectives to develop also atlases for other alternative techniques as treatment in prone position.

Patterns of locoregional failure in women with early-stage breast cancer treated by whole breast irradiation in the lateral isocentric decubitus position: Large-scale single-centre experience.

PURPOSE: The purpose of this study was to evaluate locoregional control and describe the patterns of failure in patients with breast cancer receiving whole breast radiotherapy in the isocentric lateral decubitus position technique. PATIENTS AND METHODS: In a series of 832 consecutive female patients with early-stage breast cancer including invasive and in situ tumours treated by breast-conserving surgery followed by three-dimensional conformal whole breast irradiation in the isocentric lateral decubitus position between 2005 and 2010, all patients who experienced locoregional recurrence were studied. Five-year recurrence-free and overall survival rates were calculated. Regional recurrence mapping patterns were also determined. RESULTS: The median age of this series of 832 women was 61.5 years (range: 29-90 years). Various types of fractionation were used: 50Gy in 25 fractions (17.9%), 66Gy in 33 fractions (50Gy in 25 fractions to breast followed by sequential boost to tumour bed to a total dose 66Gy in 33 fractions.) (46.5%), 40Gy in 15 fractions or 41.6Gy in 13 fractions (26.1%) and 30Gy in 5 fractions (9.5%). With a median follow-up of 6.4 years, only 36 patients experienced locoregional recurrence and no association with the fractionation regimen was identified (P=0.2). In this population of 36 patients, 28 (3.3%) had "in-breast" local recurrences (77.8%), two had local recurrences and regional lymph node recurrence (5.6%), and six had regional lymph node recurrence only (in non-irradiated areas; 16.6%). The median time to recurrence was 50 months. Complete mapping of patterns of recurrences was performed and, in most cases, local recurrences were situated adjacent to the primary tumour bed. Cases of local recurrences presented a significantly lower distant metastasis rate (P<0.001) and had a significantly longer overall survival compared to patients with regional lymph node recurrence (P<0.001). However, multivariate Cox regression analysis showed that the site of recurrence had no significant impact on overall survival (P=0.14). CONCLUSION: The results of this study indicate a low local recurrence rate. Further careful follow-up and recording of recurrences is needed to improve the understanding of patterns of recurrence.