Management of oligometastatic/metastatic sarcomas and place of local treatments with focus on modern radiotherapy approaches.

Soft tissue sarcomas are a rare and heterogeneous disease. For localized disease, treatment is based on surgery and radiotherapy with or without chemotherapy depending on risk factors. Upfront metastases are present in 7 to 20% of cases, and are localized to the lungs in most of cases. Disseminated disease is generally considered incurable but in selected cases, aggressive local treatment of metastases allowed long survival. Treatment of primary tumour is often debated. Our purpose is to evaluate the literature concerning the role of radiotherapy in the management of primary metastatic soft tissue sarcomas.

Early phase trials in soft-tissue sarcomas: clinical benefit of inclusion in early lines of treatment, molecular screening, and histology-driven trials.

BACKGROUND: The prognosis of patients with advanced soft-tissue sarcomas (STS) remains dismal, and systemic therapeutic options are limited. Early phase trials are becoming increasingly safe and effective. This study aimed to identify the prognostic factors for progression-free survival (PFS). PATIENTS AND METHODS: This retrospective analysis included all STS patients participating in early phase trials at Gustave Roussy and Léon Bérard between 1 January 2012 and 31 December 2020. RESULTS: Overall, 199 patients accounted for 214 inclusions in advanced STS. The most frequent histotypes were well-differentiated/dedifferentiated liposarcomas (n = 55), leiomyosarcomas (n = 53), synovial sarcomas (n = 22), undifferentiated pleomorphic sarcomas (n = 15), angiosarcomas (n = 12), and myxoid liposarcomas (n = 10). The median PFS was 2.8 months (95% confidence interval 2.7-4.1 months). The median PFS in the first, second, and later lines was 8.3, 5.4, and 2.6 months, respectively (P = 0.00015). The median PFS was 2.8 months in case of molecular screening, 4.1 months in case of histology-driven screening, and 1.6 months (P = 0.00014) in the absence of either screening modalities. In univariate analysis, histotype (P = 0.026), complex genomics (P = 0.008), number of prior lines (P < 0.001), prior anthracyclines (P < 0.001), number of metastatic sites (P = 0.003), liver metastasis (P < 0.001), lung metastasis (P < 0.001), absence of molecular or histology-driven screening (P < 0.001), first-in-human trials (P < 0.001), dose-escalation cohorts (P = 0.011), and Royal Marsden Hospital (RMH) score >1 (P < 0.001) were significantly associated with shorter PFS. In multivariate analysis, independent prognostic factors for shorter PFS were myxoid liposarcoma (P = 0.031), ≥2 prior lines of treatment (P = 0.033), liver metastasis (P = 0.007), and RMH score >2 (P = 0.006). Factors associated with improved PFS were leiomyosarcomas (P = 0.010), molecular screening (P = 0.025), and histology-driven screening (P = 0.010). The median overall survival rates were 36.3, 12.6, and 9.2 months in the first, second, and later lines, respectively (P = 0.0067). The grade 3-4 toxicity rate was 36%. CONCLUSIONS: Early phase trials provide an active therapeutic option for STS, even in first-line settings. Molecular screening and histology-driven trials further improve the clinical benefit.

Conformal radiotherapy in management of soft tissue sarcoma in adults.

We present the update of the recommendations of the French society of radiation oncology on soft tissue sarcomas. Currently, the initial management of sarcomas is very important as it may impact on patients' quality of life, especially in limb soft tissue sarcomas, and on overall survival in trunk sarcomas. Radiotherapy has to be discussed within a multidisciplinary board meeting with results of biopsy, eventually reexamined by a dedicated sarcoma pathologist. The role of radiotherapy varies according to localization of soft tissue sarcoma. It is part of the standard treatment in grade 2 and 3 sarcomas of the extremities and superficial trunk>5cm. In case of R1 or R2 resection, reexcision should be discussed. In such cases, it may be delivered preoperatively (50Gy/25 fractions of 2Gy) or postoperatively. In retroperitoneal sarcomas, preoperative conformal radiotherapy with or without modulated intensity cannot be proposed systematically in daily practice. Concomitant chemoradiotherapy cannot be considered a standard treatment. Intensity-modulated radiotherapy has become widely available. Other soft tissue sarcoma sites such as trunk, head and neck and gynaecological soft tissue sarcomas will be addressed, as well as other techniques that may be used such as brachytherapy and proton therapy.

[Rôle of radiotherapy for sarcomas]. / Place de la radiothérapie dans la prise en charge des sarcomes.

The quality of the initial management of sarcomas is fundamental because it conditions the patient's quality of life and his overall survival. Radiotherapy should be discussed in a multidisciplinary consultation meeting within the framework of the Netsarc+network. The place of radiotherapy in patients with soft tissue or bone sarcoma depends on the histology and tumour location, knowing that it is most often associated with surgery which remains the main treatment. It is part of the standard treatment for grade II and III deep limb sarcomas of 5cm or greater in size and Ewing's sarcomas. In these indications, conformal radiotherapy with modulation of intensity is used routinely, in combination with IGRT. In other locations, such as retroperitoneal sarcomas or uterine sarcomas, radiotherapy is not a standard of care and must be discussed according to the prognostic criteria related to the patient, the tumour, and the previously received treatments. New techniques, such as proton therapy, hadron therapy (carbon ions) are techniques particularly suited to bone sarcomas considered to be radioresistant. However, large prospective trials are lacking in these rare indications, explaining the lack of recommendations of a high level of evidence.

Medulloblastomas in adolescents and adults - Can the pediatric experience be extrapolated?

Adult medulloblastomas are orphan diseases that differ from their pediatric counterpart. Most are classified as classic or desmoplastic and fall in the SHH subgroup, mainly with loss-of-function mutations in PTCH1 and some by TP53-mutation due to underlying germline mutation. Activation of the WNT pathway is sporadic, although underlying Turcot syndrome may be present. One-third of tumors are issued from group 4. Most adult studies are small non-randomized retrospective heterogeneous studies performed at a single center with short follow-up. Standard craniospinal irradiation followed by maintenance chemotherapy (CCNU, cisplatin-vincristine) results in a 4-year event-free survival (EFS) and overall survival (OS) of 68% and 89% respectively in standard-risk adults, and in a 4-year EFS and OS of 50% and 90%, respectively in high-risk adults. Several pooled analyses point out the potential role of chemotherapy in adults. The feasibility of pediatric protocols in adults is sometimes hampered because of blood and peripheral nerve toxicity. In the near future, subgroups of medulloblastomas may be treated by personalized therapies. With prolonged follow-up, adults fare worse. Long-term sequelae and second line treatment are not well defined in adults. Prospective studies are ongoing to define optimal first-line and relapse treatments.

Clinical management of adolescents and young adults suffering from sarcoma in the French Rhône-Alpes region: A prospective exhaustive cohort with 10 years follow up.

INTRODUCTION: Survival of adolescents and young adults (AYA) with sarcoma is lower than in younger patients. The objective of this study was to describe the regional healthcare circuits, the differences in the management between adult, paediatric and mixed units and to assess the prognostic impact of compliance with clinical practice guidelines (CPGs) on overall survival (OS) and on relapse free survival (RFS). MATERIALS AND METHODS: Retrospective analysis of the management and long term follow-up of all 13-25 year old patients with a sarcoma diagnosed in the Rhône-Alpes area between 2000 and 2005. RESULTS: 140 patients satisfied inclusion criteria and were selected. The majority of 13-25 year old patients were treated in paediatric units. Joint management resulted in a higher rate of discussion in multidisciplinary tumour board, inclusion in clinical trials, and fertility preservation. Non-compliance with guidelines was observed in 65% of cases. Overall compliance was not reported to correlate to survival. Compliance of radiotherapy with CPG's seemed associated with a better prognosis for OS (HR = 0.20, 95% CI = [0.10-0.40]; p < 0.0001) and RFS (HR = 0.18, 95% CI = [0.09-0.37; p < 0.0001) as well as compliance of surgery for OS (HR = 0.43, 95% CI = [0.23-0.81]; p = 0.01). Multivariate Cox regression analysis revealed other independent predictors of OS like age at diagnosis, stage and histological subtype. CONCLUSIONS: Management of AYA in joint units seems to improve the quality of care. Compliance of surgery and radiotherapy with CGP's seems to improve survival.

Pre- and postoperative radiotherapy for extremity soft tissue sarcoma: Evaluation of inter-observer target volume contouring variability among French sarcoma group radiation oncologists.

PURPOSE: The purpose of this study was to evaluate, during a national workshop, the inter-observer variability in target volume delineation for primary extremity soft tissue sarcoma radiation therapy. METHODS AND MATERIALS: Six expert sarcoma radiation oncologists (members of French Sarcoma Group) received two extremity soft tissue sarcoma radiation therapy cases 1: one preoperative and one postoperative. They were distributed with instructions for contouring gross tumour volume or reconstructed gross tumour volume, clinical target volume and to propose a planning target volume. The preoperative radiation therapy case was a patient with a grade 1 extraskeletal myxoid chondrosarcoma of the thigh. The postoperative case was a patient with a grade 3 pleomorphic undifferentiated sarcoma of the thigh. Contour agreement analysis was performed using kappa statistics. RESULTS: For the preoperative case, contouring agreement regarding GTV, gross tumour volume GTV, clinical target volume and planning target volume were substantial (kappa between 0.68 and 0.77). In the postoperative case, the agreement was only fair for reconstructed gross tumour volume (kappa: 0.38) but moderate for clinical target volume and planning target volume (kappa: 0.42). During the workshop discussion, consensus was reached on most of the contour divergences especially clinical target volume longitudinal extension. The determination of a limited cutaneous cover was also discussed. CONCLUSION: Accurate delineation of target volume appears to be a crucial element to ensure multicenter clinical trial quality assessment, reproducibility and homogeneity in delivering RT. radiation therapy RT. Quality assessment process should be proposed in this setting. We have shown in our study that preoperative radiation therapy of extremity soft tissue sarcoma has less inter-observer contouring variability.

Genomic alterations and radioresistance in breast cancer: an analysis of the ProfiLER protocol.

BACKGROUND: Breast cancer (BC) patients with comparable prognostic features have heterogeneous outcomes, party related to a possible radiotherapy resistance leading to local-regional recurrences (LRR). The objective of the present study was to identify predictive molecular biomarkers of LRR of BC. PATIENTS AND METHODS: Genetic profile of 146 BC patients' tumours included in the ProfiLER clinical trial (NC01774409) between 2013 and 2016 were analysed using next-generation-sequencing and comparative-genomic-hybridization tests. Patients and tumour characteristics were retrospectively collected and analysed for association with genomic rearrangements (mutations, amplification, deletions). Only gene alterations observed in >3% of the tumours were selected. RESULTS: A total of 193 genomic rearrangements were identified, and 16 were observed in >3% of tumours. One was statistically correlated to the risk of local relapse. A median loco-regional progression-free survival (LRPFS) of 23.6 years was reported for PIK3CA mutation carriers (n = 31, 21.2%) versus 9.9 years for PIK3CA wild-type patients (HR 0.27, 95% CI 0.12-0.65, P = 0.002 in univariate analysis). PIK3CA mutation was identified as an independent protective factor on LRR using multivariate analysis (HR 0.29, 95% CI 0.09-0.99, P = 0.047). All other mutations, amplifications or deletions were not found associated with LRPFS. CONCLUSION: PIK3CA mutation was associated with a lower risk of local relapse in this population of BCs. This is consistent with recent studies suggesting PIK3CA to be part of biological pathways impacting the radiosensitivity.

[Spinal stereotactic body radiotherapy: French assessment in 2016]. / État des lieux de la radiothérapie en conditions stéréotaxiques vertébrale en France en 2016.

PURPOSE: Stereotactic body radiotherapy to vertebral column remains uncommon practice and only relevant in selected group of patients. The main objective of the study was to describe the current state of medical practices of stereotactic body radiotherapy to vertebral column in France in 2016 and to assess the diversity of practices to identify areas for improvement and establish a common database set for this technique. MATERIALS AND METHODS: A questionnaire was written with contribution of a medical physicist, a radiation oncologist, an information technologist and a radiotherapy resident. The questionnaire was distributed online to a radiation oncologists and a medical physicists partner of selected French radiotherapy specialized centres that provide stereotactic body radiotherapy to vertebral metastasis from April to June 2016. The questionnaire surveyed the following topics: patients' selection, simulation, targeted volume and organs at risk delineation, prescription, dosimetric implementation and image guidance. RESULTS: A total of 31 centres were surveyed. Seventy eight per cent of centres (n=21) completed the questionnaire. The "ideal" patient for spine stereotactic radiotherapy according to these institutions has a good performance status, a long life expectancy, controlled primary tumour with oligometastatic spread. The most prescribed protocol was 30Gy in three fractions. For clinical target volume delineation, about two thirds of centres used the International Spine Radiosurgery Consortium (ISRC) recommendations (Noël G et al.,2006). CONCLUSION: This study identified some consistency of practices in some aspects despite the lack of consensus guidelines. Nevertheless, further studies are needed to establish consensus of planning and treatment.

[Radiotherapy of adult soft tissue sarcoma]. / Radiothérapie des sarcomes des tissus mous de l'adulte.

Incidence of soft tissue sarcoma is low and requires multidisciplinary treatment in specialized centers. The objective of this paper is to report the state of the art regarding indications and treatment techniques of main soft tissue sarcoma localisations.

[Management of soft tissues sarcoma of the limbs by external beam radiation therapy]. / Prise en charge des sarcomes des tissus mous des membres par radiothérapie externe.

Soft tissue sarcomas are rare tumours. Conservative surgery followed by postoperative radiation therapy represents the gold standard in the majority of cases. Postoperative radiotherapy improves local control without affecting survival. Besides the quality of surgical excision, which remains the major prognostic factor, the importance of the irradiation volume and particularly margins used in external beam radiotherapy were also found to influence local control of the disease. In this study, we propose to conduct a literature review on the present state of our knowledge on this subject in the form of an articulated controversy: in favour or opposed to large margins in external radiotherapy.

Identification of a candidate biomarker from perfusion MRI to anticipate glioblastoma progression after chemoradiation.

OBJECTIVE: To identify relevant relative cerebral blood volume biomarkers from T2* dynamic-susceptibility contrast magnetic resonance imaging to anticipate glioblastoma progression after chemoradiation. METHODS: Twenty-five patients from a prospective study with glioblastoma, primarily treated by chemoradiation, were included. According to the last follow-up MRI confirmed status, patients were divided into: relapse group (n = 13) and control group (n = 12). The time of last MR acquisition was tend; MR acquisitions performed at tend-2M, tend-4M and tend-6M (respectively 2, 4 and 6 months before tend) were analyzed to extract relevant variations among eleven perfusion biomarkers (B). These variations were assessed through R(B), as the absolute value of the ratio between ∆B from tend-4M to tend-2M and ∆B from tend-6M to tend-4M. The optimal cut-off for R(B) was determined using receiver-operating-characteristic curve analysis. RESULTS: The fraction of hypoperfused tumor volume (F_hPg) was a relevant biomarker. A ratio R(F_hPg) ≥ 0.61 would have been able to anticipate relapse at the next follow-up with a sensitivity/specificity/accuracy of 92.3 %/63.6 %/79.2 %. High R(F_hPg) (≥0.61) was associated with more relapse at tend compared to low R(F_hPg) (75 % vs 12.5 %, p = 0.008). CONCLUSION: Iterative analysis of F_hPg from consecutive examinations could provide surrogate markers to predict progression at the next follow-up. KEY POINTS: • Related rCBV biomarkers from DSC were assessed to anticipate GBM progression. • Biomarkers were assessed through their patterns of variation during the follow-up. • The fraction of hypoperfused tumour volume (F_hP g ) seemed to be a relevant biomarker. • An innovative ratio R(F_hP g ) could be an early surrogate marker of relapse. • A significant time gain could be achieved in the management of GBM patients.

Effect on survival of local ablative treatment of metastases from sarcomas: a study of the French sarcoma group.

AIMS: Recent data suggest that patients with pulmonary metastases from sarcomas might benefit from ablation of their metastases. Some data are available regarding osteosarcomas/angiosarcomas and lung metastases. The purpose of this study was to assess the efficacy of local ablative treatment on the survival of patients with oligometastases (one to five lesions, any metastatic site, any grade/histology) from sarcomas. MATERIALS AND METHODS: A multicentric retrospective study of the French Sarcoma Group was conducted in sarcoma patients with oligometastases who were treated between 2000 and 2012. Survival was analysed using multivariate sensitivity analyses with propensity scores to limit bias. RESULTS: Of the 281 patients evaluated, 164 patients received local treatment for oligometastases between 2000 and 2012. The groups' characteristics were similar in terms of tumour size and remission of the primary tumours. The median follow-up was 25.7 months; 129 (45.9%) patients had died at this point. The median overall survivals were 45.3 (95% confidence interval = 34-73) months for the local treatment group and 12.6 for the other group (95% confidence interval = 9.33-22.9). Survival was better among patients who received local treatment (hazard ratio = 0.47; 95% confidence interval = 0.29-0.78; P < 0.001). Subgroup analyses revealed similar findings in the patients with single oligometastases (hazard ratio = 0.48; 95% confidence interval = 0.28-0.82; P = 0.007); a significant benefit was observed for grade 3, and a trend was observed for grade 2. CONCLUSION: Local ablative treatment seemed to improve the overall survival of the patients who presented with oligometastatic sarcomas, including soft tissue and bone sarcomas. The survival benefit remained after repeated local treatments for several oligometastatic events. Surgery yielded the most relevant results, but alternative approaches (i.e. radiofrequency ablation and radiotherapy) seemed to be promising. The relevance of these results is strengthened by our analysis, which avoided biases by restricting the population to patients with oligometastatic disease and used propensity scores.

REBECA: a phase I study of bevacizumab and whole-brain radiation therapy for the treatment of brain metastasis from solid tumours.

BACKGROUND: Brain metastases (BMs) are associated with a poor prognosis. Standard treatment comprises whole-brain radiation therapy (WBRT). As neo-angiogenesis is crucial in BM growth, combining angiogenesis inhibitors such as bevacizumab with radiotherapy is of interest. We aimed to identify the optimal regimen of bevacizumab combined with WBRT for BM for phase II evaluation and provide preliminary efficacy data. PATIENTS AND METHODS: In this multicentre single-arm phase I study with a 3 + 3 dose-escalation design, patients with unresectable BM from solid tumours received three cycles of bevacizumab at escalating doses [5, 10 and 15 mg/kg every 2 weeks at dose levels (DL) 0, 1 and 2, respectively] and WBRT (30 Gy/15 fractions/3 weeks) administered from day 15. DL3 consisted of bevacizumab 15 mg/kg with WBRT from day 15 in 30 Gy/10 fractions/2 weeks. Safety was evaluated using NCI-CTCAE version 3. BM response (RECIST 1.1) was assessed by magnetic resonance imaging at 6 weeks and 3 months after WBRT. RESULTS: Nineteen patients were treated, of whom 13 had breast cancer. There were no DLTs. Grade 1-2 in-field and out-field toxicities occurred for five and nine patients across all DLs, respectively, including three and six patients (including one patient with both, so eight patients overall) of nine patients in DL3. One patient experienced BM progression during treatment (DL0). At the 3-month post-treatment assessment, 10 patients showed a BM response: one of three treated at DL0, one of three at DL1, two of three at DL2 and six of seven at DL3, including one complete response. BM progression occurred in five patients, resulting in two deaths. The remaining patient died from extracranial disease progression. CONCLUSION: Bevacizumab combined with WBRT appears to be a tolerable treatment of BM. DL3 warrants further efficacy evaluation based on the favourable safety/efficacy balance. ClinicalTrials.gov Identifier: NCT01332929.

Adjuvant radiotherapy for extremity and trunk wall atypical lipomatous tumor/well-differentiated LPS (ALT/WD-LPS): a French Sarcoma Group (GSF-GETO) study.

BACKGROUND: The role of adjuvant radiotherapy (RT) in the management of atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WD-LPS) remains controversial. METHODS: Two hundred eighty-three patients with operable ALT/WD-LPS, no history of previous cancer, chemotherapy (CT) or RT, treated between 1984 and 2011 registered in the Conticabase database were included and described. Overall (OS), progression-free survival (PFS) and time to local relapse (TTLR) were evaluated from the time of first treatment. RESULTS: Three of 20 centers enrolled 58% of the patients. Median age at diagnosis was 61 (range 25-94) years, 147 patients (52%) were males, 222 (78%) patients had their primary tumor located in an extremity while 36 (13%) and 25 (9%) had tumors involving the girdle and the trunk wall, respectively. The median size of primary tumors was 17 cm (range 2-48 cm). Adjuvant RT was given to 132 patients (47%). Patients who received adjuvant RT had larger tumors (P = 0.005), involving more often the distal limbs (P < 0.001). Use of adjuvant RT varied across centers and along the study period. Other characteristics were balanced between the two groups. Median follow-up was 61.7 months. None of the patients developed metastasis during follow-up. The 5-year local relapse-free survival rates were 98.3% versus 80.3% with and without adjuvant RT, respectively (P < 0.001). Once stratified on time period (before/after 2003), adjuvant RT, tumor site and margin status (R0 versus other) were independently associated with TTLR. No OS difference was observed (P = 0.105). CONCLUSION: In this study, adjuvant RT following resection of ALT/WD-LPS was associated with a reduction of LR risk.

Patterns of care and survival of glioblastoma patients: a comparative study between 2004 and 2008 in Lyon, France.

INTRODUCTION: The treatment of glioblastomas (GBMs) has changed significantly since 2005. However, the extent to which this change has improved overall survival (OS) of patients treated outside clinical trials remains to be determined. METHODS: We compared the patterns of care and OS of all GBM patients diagnosed in 2004 (n=105) and in 2008 (n=130) in our center. RESULTS: Younger patients (aged<70 years) diagnosed in 2008 received temozolomide radiochemotherapy as the initial treatment and bevacizumab at recurrence more frequently than those diagnosed in 2004 (69% vs 26% P<10(-4) and 41% vs 3%, P<10(-4), respectively). Elderly patients (aged≥70 years) diagnosed in 2008 received an oncological treatment (radiotherapy and/or chemotherapy) more frequently than those diagnosed in 2004 (67% vs 38%, P=0.006). The patients diagnosed in 2008 had longer OS than those diagnosed in 2004 (10.5 months vs 5.3 months, P=0.001). This finding was true for both younger and elderly patients (15.3 months vs 8.9 months, P=0.02 and 6.4 months vs 3.2 months, P=0.0002, respectively) and when considering only IDH1 wild-type patients (8.9 months vs 5.3 months, P=0.004). CONCLUSION: In our center, the change in the patterns of care for GBMs between 2004 and 2008 has been associated with a significant improvement in OS.

[Radiotherapy for brain tumors: which margins should we apply?]. / Radiothérapie des tumeurs cérébrales : quelles marges ?

Radiotherapy is a major modality in the treatment of brain tumours. The target volumes definition has to be precise for the radiation planification. The gross target volume (GTV) is most of the time delineated within the fusion of the planning CT scan with the appropriated MRI sequences. The clinical target volume (CTV) definition is more complex: it varies in time following the evolution of scientific knowledge and also depending of the school of thought. This article offers a review of the literature about the margins applied in brain tumours radiotherapy for gliomas (high grade, anaplastic, low grade and brain stem gliomas), embryologic tumours (medulloblastomas and primitive neuroectodermal tumours [PNET]), ependymomas, atypical teratoid rahbdoid tumours (ATRT), craniopharyngiomas, pineal gland tumours, primary central nervous cell lymphomas, meningiomas and schwannomas. New imaging modalities such as diffusion-weighted imaging, dynamic contrast enhanced, spectroscopic MRI and PET scan will allow us to delineate more precisely the target volumes and to realise dose-painting by adapting the dose to the tumour metabolism.

Results of a phase II pilot study of moderate dose radiotherapy for inoperable desmoid-type fibromatosis--an EORTC STBSG and ROG study (EORTC 62991-22998).

BACKGROUND: To determine the activity of radiotherapy in patients with inoperable desmoid-type fibromatosis (DF) a multicenter prospective phase II trial was carried out. MATERIALS AND METHODS: Patients with inoperable progressive disease of primary, recurrent or incompletely resected lesions received a dose of 56 Gy in 28 fractions. Follow-up MRI studies were carried out every 3 months for 2 years and thereafter every 6 months. The primary end point was local control rate at 3 years, estimated by a nonparametric method for interval-censored survival data. Secondary end points were objective tumor response, acute and late toxic effect. RESULTS: Forty-four patients (27 F/17 M) were enrolled from 2001 to 2008. Median age was 39.5 years. Main tumor sites included trunk 15 (34.1%) and extremities 27 (61.3%). Median follow-up was 4.8 years. The 3-year local control rate was 81.5% (90% one-sided confidence interval 74% to 100%). Best overall response during the first 3 years was complete response (CR) 6 (13.6%), partial response (PR) 16 (36.4%), stable disease 18 (40.9%), progressive disease 3 (6.8%) and nonassessable 1 (2.3%). Five patients developed new lesions. After 3 years, the response further improved in three patients: (CR 2, PR 1). Acute grade 3 side-effects were limited to skin, mucosal membranes and pain. Late toxic effect consisted of mild edema in 10 patients. CONCLUSIONS: Moderate dose radiotherapy is an effective treatment of patients with DF. Response after radiation therapy is slow with continuing regression seen even after 3 years.

[Regional recurrence of triple-negative breast cancer: interest of systematic adjuvant lymph node irradiation?]. / Récidives régionales chez les patientes présentant un cancer du sein triple-négatif : intérêt d'une irradiation ganglionnaire adjuvante systématique ?

OBJECTIVE: To evaluate the percentage of regional recurrence (RR) in patients with triple-negative (TN) N0 breast cancer in order to consider the interests of a systematic adjuvant nodal irradiation. PATIENTS AND METHODS: Between February 1996 and June 2009, 249 patients were treated for TN breast cancer in Léon-Bérard center (Lyon, France). All patients received first surgical treatment followed or not by chemotherapy or radiotherapy. We excluded patients with metastasis at diagnosis, patients who were initially irradiated regional lymph node, patients which ER, PR and/or HER2 status was not known and patients who didn't have standard treatment. Ultimately, 100 patients were included. RESULTS: Two patients (2%) developed regional recurrence (1 sub and supraclavicular recurrence and 1 supraclavicular recurrence). The median follow-up was 34 months (95% CI: 29,2 to 37,4). The survival rate at 3 years was 98% (95% CI: 90-99). Our study showed no differences in terms of RR between TN cancers and not TN cancers for a median followed up of 34 months. CONCLUSION: The results of our study do not suggest that patients with TN breast cancer should receive systematic nodal adjuvant radiotherapy.