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.

Radiation dose to the low axilla in patients treated for early-stage breast cancer by locoregional intensity-modulated radiotherapy (IMRT).

PURPOSE: To determine the dose received by the low axilla during locoregional radiotherapy (RT) for early-stage breast cancer and to assess the impact of the treatment technique (three-dimensional conformal radiotherapy (3D-CRT) or rotational IMRT (VMAT) or helical tomotherapy (HT). MATERIALS AND METHODS: The dosimetric study was performed on patients receiving normofractionated (NFRT - 50Gy in 25 fractions) or hypofractionated (HFRT - 40Gy in 15 fractions) locoregional radiotherapy (breast or chest wall and internal mammary, supraclavicular and infraclavicular nodes±axillary nodes) by 3D-CRT or VMAT or HT at the Institut Curie Paris. Patients treated by breast-conserving surgery received a boost dose of 16Gy and 10Gy to the tumour bed, respectively. RESULTS: Sixty-eight patients treated by RT from February 2017 to January 2019 were studied. The mean dose received by the low axilla when it was not part of the target volume was 30.8Gy, 41.0Gy and 44.4Gy by 3D-CRT, VMAT and HT, respectively for NFRT and 24.2Gy, 33.0Gy and 34.9Gy, respectively, for HFRT. With NFRT, 4.1% of the axilla received 95% (V95) of the prescribed dose by 3D-CRT compared to 24.5% and 33.6% by VMAT and HT, respectively; with HFRT, V95 was 3.9%, 19.5% and 24.1%, respectively. CONCLUSION: The axilla receives a non-negligible dose during locoregional radiotherapy; this dose is greater when VMAT or HT are used. Prospective studies must be conducted to assess the impact of this axillary dose in terms of morbidity, which currently remains unknown.

Clinical and dosimetric impact of totally implantable venous access devices in radiotherapy of supra diaphragmatic Hodgkin Lymphoma.

PURPOSE: To evaluate attenuation of the totally implantable vascular access device (TIVAD) and assess its clinical and dosimetric impact on radiotherapy (RT) of lymphoma patients. MATERIALS AND METHODS: The first part of the study consisted of an in vitro approach by irradiating the TIVAD with different electron and photon energies. The attenuation data measured were compared with data calculated by our treatment planning system. All patients treated by radiotherapy for Hodgkin's lymphoma with their TIVAD in the target volume were then reviewed to assess the clinical outcome and dosimetric comparison using different plan metrics. All patients were treated by 3D conformal radiotherapy (3DCRT) or intensity-modulated radiotherapy delivered by Helical Tomotherapy (HT). RESULTS: Nineteen patients treated for stage I-III HL were studied. Seven patients were treated exclusively on the side of TIVAD and 12 were treated bilaterally. Median prescription dose was 30Gy. No significant clinical or dosimetric differences were observed between the side of the TIVAD and the contralateral side in patients treated bilaterally. HT resulted in a significantly higher conformity index (P<0.0022) and a significantly lower healthy tissue coverage (P=0.0008) than 3DCRT. The observed attenuation was 79% for 6 MeV, 59% for 9 MeV, and 46% for 12 MeV for electrons and 9% for 4 MV, 8% for 6 MV, 5% for 10 MV and 15 MV and 3% for 20 MV for X photons. CONCLUSION: TIVADs induce significant beam attenuation when using electrons, which can be overcome by using high-energy photons or by creating an exclusion zone in when HT is used.

Angiosarcoma associated with radiation therapy after treatment of breast cancer. Retrospective study on ten years.

PURPOSE: The breast sarcoma induced by radiation therapy is rare but increasing, given the increased long-term survival of patients receiving radiation therapy. Fibrosarcoma, histiocytofibroma and angiosarcoma are the most common breast sarcoma. Angiosarcoma is the most common after breast cancer treated by radiation therapy, often diagnosed too late, with a severe prognosis and a high rate of recurrence. However, because of the low incidence of angiosarcoma associated with radiation therapy (AAR), the benefit of radiation therapy in breast cancer treatment outweighs the risk to develop angiosarcoma. The aim of this study is to evaluate these rare cases of AAR diagnosed in eastern Belgium in comparison to the data from the literature. PATIENTS AND METHODS: Nine cases of AAR after radiation for breast ductal carcinoma were included in this retrospective study. AAR was diagnosed according to Cahan criteria between January 2007 and December 2016. Latency, incidence, management and prognosis are comparable to the literature. RESULTS, CONCLUSION: The median latency was 10 (4-24) years, the incidence of AAR in the East Belgian area was 0.09% of the patients irradiated on the same period. Patients were treated by surgery with wide local excision with or without reconstructive surgery, without radiotherapy and chemotherapy treatment. Kaplan-Meier analysis showed median overall survival of 61.8 months, patient survival of 55.6% at one year and 29.6% at five years. With the constant progress of medicine and its technologies, it would be possible to limit the occurrence of AAR or to diagnose it at an earlier stage.

[Immunotherapy and radiotherapy for management of breast cancer: Rational and overview on clinical practice]. / Immunothérapie et radiothérapie dans la prise en charge du cancer du sein : rationnel et synthèse de la littérature sur les applications cliniques actuelles.

The discovery of immunotherapy led to understand the major role of immune system during the tumor process. Conventional treatments, such as chemotherapy, are directly tumoricidal. New drugs are developed to target specifically the immune system to make it regain its ability to recognize and eliminate cancer cells. Radiotherapy is used for a long time for its local action, but its systemic role, based on its impact on immunity, is now better known. Breast cancer was wrongly considered poorly immunogenic and put aside the amazing progress in this new area of treatment. In this article, we would like to present the pre-clinical and clinical rationales to associate immunotherapy to radiotherapy in the management of breast cancer.

Protontherapy versus best photon for mediastinal Hodgkin lymphoma: Dosimetry comparison and treatment using ILROG guidelines.

The purpose of this work was reducing treatment-related toxicity for Hodgkin lymphomas using practical procedure inspired by the ILROG guidelines. Reporting the first case of localized Hodgkin lymphoma treated with protontherapy in France. A 24-year-old female with mediastinal, bulky, localized, mixed-cellularity, classic Hodgkin lymphoma required an involved-site radiation therapy after complete response following polychemotherapy. Three-dimensional conformal radiation therapy was not acceptable due to high doses to breasts, heart and lungs. We realized a four-dimensional computed tomography (CT) to evaluate target movements and another CT with gating and breath-hold technique. Delineation was performed on both CT using the initial fluorodeoxyglucose positron-emission tomography/CT. One dosimetric plan with rotational intensity-modulated radiation therapy with a helical Tomotherapy© was realized and compared to another one with conformational protontherapy. Ninety-five percent of the planning target volume was covered by 98 and 99% of the prescribed dose with protontherapy and helical Tomotherapy©. Protontherapy provided the best organ at risk protection. Lung and heart protections were better with protontherapy: lung mean dose (3.7Gy vs. 8.4Gy) and median dose (0.002Gy vs. 6.9Gy), heart mean dose (2.6Gy vs. 3.7Gy). Breast sparing was better for both breasts using protontherapy: right breast mean dose (2.4Gy vs. 4.4Gy) and left (1.9Gy vs. 4.6Gy). The biggest difference was seen with low doses, which were better with protontherapy: volume of lung receiving 5Gy was 17.5% vs. 54.2% with Helical Tomotherapy©. In view of these results, we decided to treat our patient with protontherapy using respiratory assessment. We delivered 30Gy (15 fractions) using protontherapy with one direct anterior field using pencil beam scanning and deep inspiration breath-hold technique. We observed only grade 1 skin erythema during treatment and no toxicity during early follow-up.

Radiotherapy in combination with nivolumab for relapsed/refractory classical Hodgkin lymphoma: About two cases.

Hodgkin lymphoma is a highly curable malignancy involving lymph nodes and the lymphatic system. Even at late stage disease, about 70% of patients will be cured with standard first line therapy. For patients who experience relapse or refractory classical Hodgkin lymphoma, the standard treatment option is high-dose chemotherapy followed by autologous stem cell rescue or transplant. However about 50% of patients will have recurrence after high-dose chemotherapy followed by autologous stem cell rescue or transplantation and have worse prognosis with median overall survival of 32% at 5 years. The anti-PD1 checkpoints inhibitors pembrolizumab and nivolumab have remarkably improved outcomes of patients with relapse of refractory classical Hodgkin lymphoma after high-dose chemotherapy followed by autologous stem cell rescue or transplantation. On the other hand, radiotherapy is an entire component of salvage therapy and its efficacy is now well established in term of local disease control in sites of relapsed or refractory Hodkin lymphoma. Defining the optimal modality and timing of radiotherapy as these new agents arrive is a challenge. An interesting approach is the combination of radiotherapy with checkpoint inhibitor and the possibility of stopping the treatment when complete response is achieved. We add to the literature two new cases of combination of radiotherapy with immunotherapy in patients who relapsed after high-dose chemotherapy followed by autologous stem cell rescue or transplantation and consolidation with brentuximab vedotin, resulting in excellent outcomes.

Whole breast radiotherapy in the isocentric lateral decubitus position: Role of the immobilization device and table on clinical results.

PURPOSE: To evaluate clinical results and the "effect bolus" based on the table design of different linear accelerators in patients with breast cancer treated by previously published whole breast irradiation in the isocentric lateral decubitus position. MATERIAL AND METHODS: We studied 248 consecutive female patients with early stage breast cancer treated by conservative surgery followed by three-dimensional conformal whole breast irradiation in the isocentric lateral decubitus position between January 2013 and February 2014. Radiotherapy was performed on linear accelerators using a Varian. The energy used was 4 and 10MV photons or 6MV photons. All patients were evaluated weekly by the radiation oncologist, acute toxicity was assessed using the NCICTC v 3.0 scale. Late toxicity and cosmetic results were evaluated 18 months after the radiotherapy. Cosmetic results were defined as excellent, good, middle or bad. RESULTS: Among the 248 women included, the median age was 67 years (range: 35-91 years). All received whole breast radiotherapy with boost in 144 patients (58%). One-hundred-twenty patients received normofractionated and 124 patients hypofractionated whole breast radiotherapy. Median follow-up was 18 months. Acute skin toxicity in the whole breast radiotherapy in the isocentric lateral decubitus position was acceptable: there was 47% of grade 1 radiodermatitis, 50% of grade 2 and 3% grade 3 and no grade 4 for normofractionated radiotherapy; 89% of grade 1 dermatitis and 11% of grade 2 for hypofractionated radiotherapy; 89.7% of grade 0-1 dermatitis and 10.3% of grade 2 for the "flash" scheme and did not differ between the three linear accelerators (P=0.2, P=0.9 and P=0.2 respectively for the normofractionated radiotherapy, hypofractionated radiotherapy and the "flash"scheme). Late toxicity was acceptable with 84% of grade 0-1 fibrosis for normofractionated radiotherapy, 94% of patients for hypofractionated radiotherapy and 77% for "flash" scheme and did not differ between the three linear accelerators (P=0.44, P=1 and P=0.22 resp.). Most of patients (81%) had an excellent or a good cosmetic outcome. CONCLUSIONS: Whole breast radiotherapy in the isocentric lateral decubitus position is well tolerated. Clinical results are comparable based on different immobilization device allowed by linear accelerators. Particularly, there was no influence of the couch on skin tolerance and cosmetic results.

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.

Anti-PD-1 immunotherapy in combination with sequential involved-site radiotherapy in heavily pretreated refractory Hodgkin lymphoma.

The purpose of this study was to assess efficacy and tolerance of anti-programmed death (PD)-1 immunotherapy in combination with sequential involved-site radiotherapy in heavily pretreated refractory Hodgkin lymphoma. In this case series, we reported the outcome of four heavily pretreated patients with refractory Hodgkin lymphoma treated by anti-PD-1 immunotherapy and involved site radiation therapy. After a median follow-up of 13-month, all patients were alive with complete metabolic response. After radiotherapy, all four patients experienced lung toxicity, which was resolved after antibiotherapy with or without corticosteroid treatment. Anti-PD-1 immunotherapy followed by involved-site radiotherapy is feasible and showed very encouraging results in heavily pretreated patients.

[Locoregional control and patterns of locoregional failure in women with breast cancer treated by highly conformal electron beam irradiation]. / Caractérisation des rechutes locorégionales chez des patientes atteintes d'un cancer du sein traité par irradiation pariétale par électrons : expérience monocentrique de l'institut Curie.

PURPOSE: The purpose of this study was to evaluate locoregional control and describe the patterns of locoregional failure in women with breast cancer irradiated by a previously described post-mastectomy highly conformal electron beam radiotherapy technique. MATERIAL AND METHODS: We included all women irradiated by post-mastectomy highly conformal electron beam radiotherapy technique for non-metastatic breast cancer between 2007 and 2011 in our department. All cases of bilateral breast cancer were excluded. All patients who experienced locoregional recurrence have been studied. Mapping patterns of regional recurrences was also performed and compared with the European Society for Radiotherapy and Oncology (ESTRO) and Radiotherapy Oncology Group (RTOG) guidelines of volume definition and delineation guidelines. RESULTS: With a median follow-up of 64 months (range: 6-102 months), 5-year locoregional recurrence-free and overall survival probabilities were 90 % (95 % confidence interval [95 %CI]: 88.1-92.4) and 90.9 % (95 %CI: 88.9-93), respectively. Among the 796 patients included in the study, 23 patients (2.9 %) presented locoregional recurrences of them only 13 (1.6%) were presented with local recurrence. The majority of them presented aggressive biological features with grade III tumours in 17 patients (74 %) with high mitotic index in 16 cases (70 %) and triple negative tumours in 12 (52 %). Lymphovascular invasion was observed in 11 cases (48 %). In 14 cases the locoregional recurrences were diagnosed at the same time as the metastatic disease whereas 4 patients presented distant metastases secondarily. Locoregional recurrences occurred in 11 cases "in field" although adequate doses and volumes were used and in 12 cases "outfield", out of irradiated volume. Local recurrences occurred in 13 patients with 12 recurrences within the irradiated volumes. Regional recurrences occurred in 13 patients with 15 lymph nodes metastases identified. Four nodal recurrences occurred outside the ESTRO clinical target volume and within the RTOG clinical target volume and two occurred outside both RTOG and ESTRO clinical target volumes. CONCLUSION: In presented series, the local recurrence resulted mostly from of biologic radio resistance whereas regional recurrences were caused by geographical miss. A number of nodal recurrences could occur outside the target volumes defined by ESTRO and RTOG.

Radiation therapy after sentinel lymph node biopsy for early stage breast cancer using a magnetic tracer: Results of a single institutional prospective study of tolerance.

PURPOSE: . The aim of the study was, through a single institutional analysis of a large population of breast cancer patients, to assess the feasibility of and the tolerance to radiotherapy after the use of magnetic detection method for sentinel lymph node biopsy. MATERIAL AND METHODS: The super paramagnetic iron oxide particles database was collected prospectively and identified 520 cases from October 2013 to December 2016 at our institution. All of them received super paramagnetic iron oxide particles injection 20minutes before the surgical procedure and some of them received also isotope technique. Injection site for super paramagnetic iron oxide particles and isotope was periareolar. Among them, 288 patients received adjuvant radiotherapy. In our study, we evaluated the tolerance of postoperative radiotherapy. RESULTS: The median age of the patients was 64 years. The median follow-up period was 16 months (range: 1-42 months). Double detection of sentinel lymph node was done in the first 30 patients (10.4%). The sentinel lymph node identification rate was 99.7% (287 out of 288). There were 34 axillary lymph node dissections, of which 58.8% were realized straightaway. The total radiation dose was 50Gy EQD2 (range: 28.5-66Gy). Regarding the occurrence of radiodermatitis, 95.8% of patients had grade 0-2 radiodermatitis and 1% had grade 3. During follow-up, 19.4% of patients developed grade 1-2 post-therapeutic fibrosis (of which 92.9% grade 1). CONCLUSION: The results of this large-scale study show that the radiotherapy after sentinel lymph node biopsy using super paramagnetic iron oxide particles is feasible, and that no increase of the toxicity was observed.

Different radiation techniques to deliver therapeutic dose to the axilla in patients with sentinel lymph node-positive breast cancer: Doses, techniques challenges and clinical considerations.

PURPOSE: To evaluate the coverage of different levels of axillary lymph nodes and organs at risk according to the field design of AMAROS study (levels I-II-III-IV), breast tangents with supraclavicular and infraclavicular fields (levels II-III-IV) and high tangent fields to the breast after breast-conserving surgery. MATERIALS AND METHODS: We delineated the axillary lymph nodes levels I-IV in 34 patients treated with breast-conserving surgery and sentinel lymph nodes biopsy. Field design according to AMAROS study - levels I-IV in patients without axillary dissection - as well as irradiation of levels II-IV used in N+ patients after axillary dissection, and also high tangent fields was simulated. Mean dose levels and volumes covered by 95% or 80% isodoses were evaluated. Doses to ipsilateral lung, heart and brachial plexus were compared. Paired t test was used. RESULTS: AMAROS study and levels II-IV plans delivered therapeutic dose to high axilla (levels II-IV), but the high tangent fields showed inefficacy to cover these volumes, P<0.001). In terms of organs at risk, especially, ipsilateral lung, AMAROS study plan was found to significantly increase the volume receiving at least 10Gy (I-IV:46.8%, II-IV: 39%), but also the volume receiving at least 20Gy (I-IV: 39.3%, II-IV: 31.3%), and V30Gy (I-IV: 34.2% vs II-IV: 26.1%), as well as the mean dose (I-IV: 18.6Gy, II-IV: 15.2Gy, P<0.001). CONCLUSIONS: The omission of axillary dissection and the axilla irradiation need is associated with high dose irradiation of the lungs, and with higher toxicity. The indication of axillary dissection or irradiation of low axilla could be individualized in relation with individual comorbidities and factors of risk.

[Technical aspects and indications of extracranial stereotactic radiotherapy]. / Place de la radiothérapie stéréotaxique extracrânienne dans la prise en charge des patients atteints de cancer.

Extracranial stereotactic radiotherapy has developed considerably in recent years and is now an important part of the therapeutic alternatives to be offered to patients with cancer. It offers opportunities that have progressively led physicians to reconsider the therapeutic strategy, for example in the case of local recurrence in irradiated territory or oligometastatic disease. The literature on the subject is rich but, yet, there is no real consensus on therapeutic indications. This is largely due to the lack of prospective, randomized studies that have evaluated this technique with sufficient recoil. We propose a review of the literature on the technical aspects and indications of extracranial stereotactic radiotherapy.

[Evaluation of an automatic delineation system for organs at risk and target lymph nodes volumes for patients treated for breast cancer]. / Évaluation d'un logiciel pour la délinéation automatique des organes à risques et des volumes cibles ganglionnaires chez des patientes prises en charge pour un cancer du sein.

PURPOSE: Intensity-modulated radiotherapy needs the strict delineation of target volumes as well as organs at risk and the time used for this procedure is long. The purpose of this study was to evaluate the Workflow Box system (Mirada Medical, UK) for automatic delineation and segmentation for everyday use of organs at risk and lymph nodes delineation in patients treated for early stage breast cancer. MATERIAL AND METHODS: Twenty patients' CT scans in treatment position for their breast cancer radiotherapy were delineated in respect of the ESTRO delineation guidelines to begin the creation of automatic delineation atlas. Then 30 other CT scans were delineated this time by the automatic delineation system and by the radiation oncologist (reference delineation plan). The precision of the delineation was evaluated using the overlap volume index and evaluation of standard deviation (SD). RESULTS: The study of organs at risk has shown that the mean overlap volumes were between 0.49 (SD=0.21) and 0.97 (ET=0.03). Five organs at risk out of nine had overlap volumes at least 0.8. The mean overlap volume for all organs at risk was 0.77 (SD=0.17). The system was less performing for the lymph nodes with a mean overlap volume of 0.43 (SD=0.1) and ranging between 0.23 (SD=0.13) and 0.52 (SD=0.1). The use of this system reduced the delineation time by 40% per patient. CONCLUSIONS: For patients with breast cancer, the system for automatic delineation and segmentation Workflow Box (Mirada Medical, UK) permitted to safely shorten the time for delineation with acceptable organs at risk delineation. Improvement of lymph node volumes is needed. A new evaluation will be realized after using the system in routine practice.

Radiotherapy of relapse-refractory follicular lymphoma.

PURPOSE: To assess the efficacy of treatment and outcomes of patients with relapsed or refractory follicular lymphoma treated with external beam irradiation. PATIENTS AND METHODS: Fifteen patients who received external beam radiotherapy for relapsed or refractory follicular lymphoma were studied. The median age was 68.3 years (range: 37.9-87.08 years) with four men and 11 women. Seven patients had early stage (I or II); eight advanced stage (III or IV). Median FLIPI score was 2. Two patients had high tumour bulk disease. Six patients had extranodal invasion, with five patients having bone marrow invasion. RESULTS: The median time of follow-up after relapse or first-line treatment in case of refractory disease was 61.9 months (range: 9.1-119.7 months). Complete response after external beam radiotherapy was seen in 11 cases (73%) and partial response in two (13%), with a median dose of 30Gy (range: 2-40Gy) and median number of fractions of 15 (range: 2-20). Eight patients (53%) relapsed after external beam radiation therapy in a median of 20.2 months, mostly out of irradiated volumes. Most patients (66%) had a disease control after one or two courses of external beam radiation therapy. At last follow-up, 86% of patients were in remission including those with salvage chemotherapy. The toxicity profile was favourable with toxicity higher than grade 1. In univariate analysis, a Follicular Lymphoma International Prognostic Index (FLIPI) score above 2 was the only predicting factor for non-control disease. CONCLUSION: For relapsed and refractory follicular lymphoma, external beam radiotherapy should be considered as an effective modality when integrated in a multimodality approach. Randomised studies are warranted to validate this strategy.

Outcome of postmastectomy radiotherapy after primary systemic treatment in patients with clinical T1-2N1 breast cancer.

PURPOSE: The role of postmastectomy radiotherapy following primary systemic treatment in patients with clinical T1-2N1 breast cancer remains a controversial issue. The purpose of this study was to evaluate the benefit of postmastectomy radiotherapy following primary systemic treatment. PATIENTS AND METHODS: Between 2005 and 2012, in two independent institutions, female patients with T1-2N1 breast cancer receiving primary systemic treatment followed by mastectomy and lymph node dissection because bad response, then treated with or without chest wall and regional lymph node irradiation have been studied retrospectively. The patients received normofractionated radiotherapy using 3D conformal photons or electron techniques. Locoregional recurrence-free survival, distant metastasis-free survival and disease-free survival were calculated using Kaplan-Meier method. Univariate analysis of potential prognostic factors was performed using log-rank test. RESULTS: Eighty-eight patients have been studied. Of them, 75 patients received postmastectomy radiotherapy. At surgery, 53 patients achieved ypN0. Median follow-up was 67 months. Postmastectomy radiotherapy significantly improved locoregional recurrence-free survival, with a 5-year rate of 96.9% versus 78.6% in the group that did not have postmastectomy radiotherapy. In the subgroup of 53 patients achieving ypN0, postmastectomy radiotherapy improved locoregional recurrence-free survival (a 5-year rate of 94.7% vs. 72.9%), distant metastasis-free survival (a 5-year rate of 92.8% vs. 75%) and disease-free survival (a 5-year rate of 92.9% vs. 62.5%). By univariate analysis, postmastectomy radiotherapy was the only significant prognostic factor affecting locoregional recurrence-free survival. CONCLUSIONS: For patients with clinical T1-2N1 disease, postmastectomy radiotherapy could significantly improve locoregional recurrence-free survival after primary systemic treatment and be even more therapeutic in the subgroup of patients with good response for primary systemic treatment by improving locoregional recurrence-free, distant metastasis-free and disease-free survival. Larger prospective studies are needed to confirm our findings.

Combined irradiation and targeted therapy or immune checkpoint blockade in brain metastases: toxicities and efficacy.

BACKGROUND: Targeted therapies (TT) and immune checkpoint inhibitors (ICI) are currently modifying the landscape of metastatic cancer management and are increasingly used over the course of many cancers treatment. They allow long-term survival with controlled extra-cerebral disease, contributing to the increasing incidence of brain metastases (BMs). Radiation therapy remains the cornerstone of BMs treatment (either whole brain irradiation or stereotactic radiosurgery), and investigating the safety profile of radiation therapy combined with TT or ICI is of high interest. Discontinuing an efficient systemic therapy, when BMs irradiation is considered, might allow systemic disease progression and, on the other hand, the mechanisms of action of these two therapeutic modalities might lead to unexpected toxicities and/or greater efficacy, when combined. PATIENTS AND METHODS: We carried out a systematic literature review focusing on the safety profile and the efficacy of BMs radiation therapy combined with targeted agents or ICI, emphasizing on the role (if any) of the sequence of combination scheme (drug given before, during, and/or after radiation therapy). RESULTS: Whereas no relevant toxicity has been noticed with most of these drugs, the concomitant use of some other drugs with brain irradiation requires caution. CONCLUSION: Most of available studies appear to advocate for TT or ICI combination with radiation therapy, without altering the clinical safety profiles, allowing the maintenance of systemic treatments when stereotactic radiation therapy is considered. Cognitive functions, health-related quality of life and radiation necrosis risk remain to be assessed. The results of prospective studies are awaited in order to complete and validate the above discussed retrospective data.

[Doses to organs at risk in conformational radiotherapy and stereotaxic irradiation: The heart]. / Doses aux organes à risque en radiothérapie conformationnelle et en radiothérapie en conditions stéréotaxiques : le cœur.

Radiation therapy of breast cancer, Hodgkin lymphoma, lung cancer and others thoracic irradiations induce an ionizing radiation dose to the heart. Irradiation of the heart, associated with patient cardiovascular risk and cancer treatment-induced cardiotoxicity, increase cardiovascular mortality. The long survival after breast or Hodgkin lymphoma irradiation requires watching carefully late treatment toxicity. The over-risk of cardiac events is related to the dose received by the heart and the irradiated cardiac volume. The limitation of cardiac irradiation should be a priority in the planning of thoracic irradiations. Practices have to be modified, using modern techniques to approach of the primary objective of radiotherapy which is to optimize the dose to the target volume, sparing healthy tissues, in this case the heart. We have reviewed the literature on cardiac toxicity induced by conformational tridimensional radiation therapy, intensity-modulated radiation therapy or stereotactic body radiation therapy, in order to evaluate the possibilities to limit cardiotoxicity. Finally, we summarise the recommendations on dose constraints to the heart and coronary arteries.