Optimizing lung cancer radiation therapy: A systematic review of multifactorial risk assessment for radiation-induced lung toxicity.

BACKGROUND: Radiation therapy (RT) is essential in treating advanced lung cancer, but may lead to radiation pneumonitis (RP). This systematic review investigates the use of pulmonary function tests (PFT) and other parameters to predict and mitigate RP, thereby improving RT planning. METHODS: A systematic review sifted through PubMed and on BioMed Central, targeting articles from September 2005 to December 2022 containing the keywords: Lung Cancer, Radiotherapy, and pulmonary function test. RESULTS: From 1153 articles, 80 were included. RP was assessed using CTCAEv.4 in 30 % of these. Six studies evaluated post-RT quality of life in lung cancer patients, reporting no decline. Patients with RP and chronic obstructive pulmonary disease (COPD) generally exhibited poorer overall survival. Notably, forced expiratory volume in one second (FEV1) and diffusing capacity of the lung for carbon monoxide (DLCO) declined 24 months post-RT, while forced vital capacity (FVC) stayed stable. In the majority of studies, age over 60, tumors located in the lower part of the lung, and low FEV1 before RT were associated with a higher risk of RP. Dosimetric factors (V5, V20, MLD) and metabolic imaging emerged as significant predictors of RP risk. A clinical checklist blending patient and tumor characteristics, PFT results, and dosimetric criteria was proposed for assessing RP risk before RT. CONCLUSION: The review reveals the multifactorial nature of RP development following RT in lung cancer. This approach should guide individualized management and calls for a prospective study to validate these findings and enhance RP prevention strategies.

Diagnostic accuracy and safety of percutaneous core needle biopsy of retroperitoneal tumours.

BACKGROUND: Histologic subtype of cancer guides treatment sequencing and the extent of surgery for retroperitoneal tumours (RPTs) but concerns persist regarding percutaneous core needle biopsy (CNB). OBJECTIVE: Endpoints were the incidence of early complications, needle tract seeding (NTS) after CNB, diagnostic accuracy. METHODS: Between 2015 and 2022, data from patients with RPT who underwent a CNB and who operated on at Institut Curie were collected. We retrospectively reviewed the medical records and microscopic analysis of both CNB and surgical specimens to evaluate the diagnostic accuracy of CNB (quantified using positive and negative predictive values, PPV/NPV). RESULTS: 313 patients underwent CNB. In 10/326 (3 %) procedures, minor complications were observed. One of 212 (0.47 %) resected RPSs exhibited a local recurrence compatible with NTS. Microscopic analysis of CNB specimens allowed the classification of tumours between groups of cancers and benign/intermediate mesenchymal tumours in 307/313 (98 %) patients. Among the 204 patients with retroperitoneal sarcoma, the overall concordance between CNB and final pathology following resection was 178/204 (87.2 %). The respective PPVs of solitary fibrous tumour, dedifferentiated liposarcoma, leiomyosarcoma and well-differentiated liposarcoma were 100 %, 98 %, 97 % and 68 %, respectively. The diagnosis of a high-grade (G 2-3) sarcoma resulted in a high specificity (97 %) and PPV (98 %) but low sensitivity (76 %). CONCLUSIONS: CNB allowed the classification of RPT in the vast majority of patients with a low morbidity rate. Concordance with final diagnosis was high for sarcomas with the exception of well-differentiated liposarcoma. As a result, CNB results should be integrated with imaging/radiomics by multidisciplinary tumour boards.

Post-operative flank irradiation using conformal versus highly conformal radiotherapy techniques for paediatric renal tumours: Results from the French registry PediaRT.

PURPOSE: Three-dimensional conformal RT (3D-RT) techniques are gold standard for post-operative flank radiotherapy (RT) in paediatric renal tumours. Recently, highly conformal RT (HC-RT) techniques have been implemented without comparative clinical data. The main objective of this multicentre study was to compare locoregional control (LRC) in children treated either with HC-RT or 3D-RT techniques. METHODS: Patients treated with post-operative flank RT for renal tumour registered in the national cohort PediaRT between March 2013 and September 2019 were included. Treatment and follow-up data, including toxicities and outcomes, were retrieved from the database. LRC was calculated, and dose reconstruction was performed in case of an event. RESULTS: Seventy-nine patients were included. Forty patients were treated with HC-RT and 39 with 3D-RT. Median follow-up was 4.5 years. Three patients had locoregional failure (LRF; 4%). HC-RT was not associated with a higher risk of LRF. Three-year LRC were 97.4% and 94.7% in the HC-RT and 3D-RT groups, respectively. The proportion of planning target volumes receiving 95% or more of the prescribed dose did not significantly differ between both groups (HC-RT 88%; 3D-RT 69%; p = .05). HC-RT was better achieving dose constraints, and a significant mean dose reduction was observed in the peritoneal cavity and pancreas associated with lower incidence of acute gastrointestinal toxicity. CONCLUSION: LRF after post-operative flank RT for renal tumours was rare and did not increase using HC-RT versus 3D-RT techniques. Dose to the pancreas and the peritoneal cavity, as well as acute toxicity, were reduced with HC-RT compared to 3D-RT.

Significant Predictors of Postoperative Morbidity After Radical Resection of Retroperitoneal Sarcoma in a Tertiary Center.

BACKGROUND: The safety of multivisceral resection of retroperitoneal sarcoma is an issue. Previous reports have investigated its associations with the pattern of resection and factors recognized mostly per operatively. METHODS: All consecutive RPS resections from May 2015 to April 2022 were studied retrospectively with respect to adverse events. Two univariate and multivariate logistic regression analyses were performed to investigate the associations between severe adverse events and factors recognized pre- and per operatively. Associations of adverse events with overall survival (OS) and local recurrence (LR) were investigated. RESULTS: A total of 265 surgical interventions corresponding to 251 patients were recorded (38 RPS surgeries/year). Severe postoperative adverse events (Clavien-Dindo ≥ 3) occurred in 50 patients (18.9%), 15 (5.6%) patients underwent an iterative laparotomy, and 6 patients (2.3%) died within 90 days. On multivariate analysis including all parameters known preoperatively, male sex, performance status, dedifferentiated liposarcoma histology, and low serum albumin level were found to be significant predictors of major complications, whereas the timing of surgery and preoperative treatment were not. On univariate analysis including all per operative parameters, transfusion requirement, operative time, number of digestive anastomoses, and pancreas and/or major arterial resection were found to entail higher operative risk. On multivariate analysis, only transfusion requirement was significant. There was no impact of postoperative adverse events on OS or LR. CONCLUSIONS: The recognition of preoperative parameters that impact safety could mitigate the extent of the surgery, specifically the resection of adherent organs not overtly invaded. For the best decision, this surgery should be performed in referral centers.

Proton therapy for adult craniopharyngioma: Experience of a single institution in 91 consecutive patients.

BACKGROUND: Craniopharyngioma (CP) in adults is a rare benign tumor associated with many morbidities, with limited contemporary studies to define treatment, and follow-up guidelines. METHODS: A single-center retrospective study was conducted on patients aged ≥ 18 years from 2006-2018 with CP and who were treated with proton therapy (PT). Late toxicity was defined as a minimum of 18 months from diagnosis. Overall survival (OS), local recurrence-free survival (LRFS), and toxicity were characterized using Kaplan-Meier and Cox regression analyses. RESULTS: Ninety-one patients met the criteria, with a median age of 37 years (range 18-82 years). PT was conducted after tumor resection in 88 patients (97%), in 64 patients (70.3%) as an adjuvant strategy and in 27 (29.7%) after recurrent disease. Three patients received exclusive PT. A median MRI follow-up of 39 months revealed 35.2% complete response, 49.5% partial response, and 9.9% stable disease. Five patients developed local recurrence (LR). The pattern of failure study showed that these five LR were within the GTV volume. The 5-year LRFS was 92.0% [CI 95% 84.90-99.60]. All the patients were alive at the end of the follow-up. Patients requiring treatment adaptation during PT tend to have a higher risk of LR (P = .084). Endocrinopathy was the most frequent grade ≥ 2 late toxicity. Among patients who were symptom-free before the start of treatment, none developed hearing toxicity but four (9.8%) developed visual disorders and 10 (11.3%) symptomatic memory impairment. Patients with large tumors had a higher risk of developing symptomatic memory impairment (P = .029). CONCLUSION: Adults with CP treated with PT have favorable survival outcomes, with acceptable late toxicity. Prospective quality-of-life and neurocognitive studies are needed to define late adverse effects better.

Final Safety and Health-Related Quality of LIfe Results of the Phase 2/3 Act.In.Sarc Study With Preoperative NBTXR3 Plus Radiation Therapy Versus Radiation Therapy in Locally Advanced Soft-Tissue Sarcoma.

PURPOSE: Act.In.Sarc (NCT02379845) demonstrated that the first-in-class radioenhancer NBTXR3, activated by preoperative radiation therapy (RT), doubled the rate of pathologic complete response after resection compared with preoperative RT alone in adult patients with locally advanced soft tissue sarcoma of the extremity or trunk wall (16.1% vs 7.9%, P = .045), and more patients achieved R0 resections (77.0% vs 64.0%, P = .042). These are the toxicity and health-related quality of life (HRQoL) results. METHODS AND MATERIALS: Act.In.Sarc randomized eligible patients 1:1 to either NBTXR3 (single intratumoral injection, volume equivalent to 10% of baseline tumor volume, at 53.3 g/L) activated by external-beam RT (arm A) or external-beam RT alone (arm B) (50 Gy in 25 fractions), followed by surgery in both arms. Here, we report the safety analyses in the all-treated population with a long-term follow-up of at least 2 years, and HRQoL in the intention-to-treat full analysis set. RESULTS: During the on-treatment period, serious adverse events (SAEs) of all grades related to NBTXR3 occurred in 10.1% (9/89) of patients (arm A), and SAEs related to RT occurred in 5.6% (5/89) (arm A) versus 5.6% (5/90) (arm B); postsurgery hospitalization owing to SAEs occurred in 15.7% (14/89) (arm A) versus 24.4% (22/90) (arm B). During the follow-up period, posttreatment SAEs (regardless of relationship) occurred in 13.5% (12/89) (arm A) versus 24.4% (22/90) (arm B). NBTXR3 did not negatively affect HRQoL; during the follow-up period, there was an improvement in most mean Toronto extremity salvage, EuroQoL 5-dimension (EQ-5D), EQ5D02-EQ visual analog scale, reintegration to normal living index, and musculoskeletal tumor rating scale scores. CONCLUSIONS: NBTXR3 did not negatively affect safety or HRQoL. Long-term safety results reinforce the favorable benefit-risk ratio of NBTXR3 plus RT.

NUT carcinoma in children, adolescents and young adults.

BACKGROUND: NUT carcinoma (NC), defined by the presence of the NUTM1 rearrangement, is an aggressive tumour associated with poor prognosis. This rare cancer is underdiagnosed and difficult to treat. OBJECTIVE AND METHODS: The primary objective of this review is to describe the clinical, radiological and laboratory features of NC in young patients. The secondary objective is to propose a consensual strategy for the French very Rare Tumour group (FRACTURE group). RESULTS: NUT-specific antibody immunostaining in cases of undifferentiated or poorly differentiated carcinoma may demonstrate the specific NUT gene rearrangement. NCs are frequently advanced stage at diagnosis and the outcome remains poor despite a global strategy that generally includes conventional combination chemotherapy with wide local therapy (surgery, radiotherapy). Chemosensitivity is frequently only transient. CONCLUSION: Recent data have shown that new targeted drugs (histone deacetylase and bromodomain and extra-terminal protein inhibitors) are promising, but their role has yet to be evaluated in NC. Centralized data review is necessary to improve our knowledge of paediatric NC. We propose a multimodal strategy based on published data and their personal experience.

Treatment related factors associated with the risk of breast radio-induced-sarcoma.

BACKGROUND AND PURPOSE: The Radiation Induced Sarcoma (RIS) is a rare but serious adverse event following radiotherapy (RT). Current RT techniques are more precise, but irradiate a larger volume at a low dose. This study aimed to describe radiation characteristics in a large series of patients suffering from RIS. MATERIALS AND METHODS: Patient-representative voxel-based anthropomorphic phantoms were used to reconstruct patient-specific RT fields for 125 patients diagnosed with RIS after primary breast cancer. For each patient, the location of the RIS onset site was determined and transferred onto the phantom as a contour. Using a treatment planning system (TPS), the dose distribution on the RIS in the phantom was calculated. RESULTS: The mean dose (Dmean) received in the area where RIS subsequently developed was 47.8 ± 11.6 Gy. The median dose in the zones where RIS later developed ranged from 11 Gy to 58.8 Gy. The median time from RT to RIS development was 8 years (range 2-32 years). Analysis for predictors of time to radiation-induced sarcoma development highlighted a significant impact of age of patient during the RT whereas in multivariable analysis chemotherapy and hormonotherapy for primary breast cancer were not associated with a significant difference in time to diagnosis of RIS. CONCLUSIONS: This study highlights that the dose received by the tissue in which the RIS developed was almost 47 Gy. These results are encouraging for the use of new RT techniques increasing volumes receiving low doses, without fear of an excess of RIS over the next 10 years.

Brachytherapy for Pediatric Patients at Gustave Roussy Cancer Campus: A Model of International Cooperation for Highly Specialized Treatments.

PURPOSE: Childhood cancer is rare, and treatment is frequently associated with long-term morbidity. Disparities in survival and long-term side effects encourage the establishment of networks to increase access to complex organ-conservative strategies, such as brachytherapy. We report our experience of an international cooperation model in childhood cancers. METHODS AND MATERIALS: We examined the outcome of all children referred to our center from national or international networks to be treated according to a multimodal organ-conservative approach, including brachytherapy. RESULTS: We identified 305 patients whose median age at diagnosis was 2.2 years (range, 1.4 months to 17.2 years). Among these patients, 99 (32.4%) were treated between 2015 and 2020; 172 (56.4%) were referred from national centers; and 133 (43.6%) were international patients from 31 countries (mainly Europe). Also, 263 patients were referred for primary treatment and 42 patients were referred for salvage treatment. Genitourinary tumors were the most frequent sites, with 56.4% bladder/prostate rhabdomyosarcoma and 28.5% gynecologic tumors. In addition to brachytherapy, local treatment consisted of partial tumor resection in 207 patients (67.9%), and 39 patients (13%) had additional external radiation therapy. Median follow-up was 58 months (range, 1 month to 48 years), 93 months for national patients, and 37 months for international patients (P < .0001). Five-year local control, disease-free survival, and overall survival rates were 90.8% (95% confidence interval [CI], 87.3%-94.4%), 84.4% (95% CI, 80.1%-89.0%), and 93.3% (95% CI, 90.1%-96.5%), respectively. Patients referred for salvage treatment had poorer disease-free survival (P < .01). Implementation of image guided pulse-dose-rate brachytherapy was associated with better local control among patients with rhabdomyosarcoma referred for primary treatment (hazard ratio, 9.72; 95% CI, 1.24-71.0). At last follow-up, 16.7% patients had long-term severe treatment-related complications, and 2 patients (0.7%) had developed second malignancy. CONCLUSIONS: This retrospective series shows the feasibility of a multinational referral network for brachytherapy allowing high patient numbers in rare pediatric cancers. High local control probability and acceptable late severe complication probability could be achieved despite very challenging situations. This cooperation model could serve as a basis for generating international reference networks for high-tech radiation such as brachytherapy to increase treatment care opportunities and cure probability.

Safe-margin surgery by plastic reconstruction in extremities or parietal trunk soft tissue sarcoma: A tertiary single centre experience.

INTRODUCTION: Tertiary centers recruit a large proportion of locally advanced or recurrent soft tissue sarcomas (STSs) that may have been preoperatively irradiated. The objective of this study was to evaluate the results of oncoplastic surgery (OPS) for patients affected by extremities or parietal trunk STS. MATERIALS AND METHODS: This retrospective study includes patients who underwent a flap reconstruction after sarcoma resection between January 2018 and December 2020 at Institut Curie. The primary endpoint was the evaluation of the impact of OPS on the quality of surgical margins. The secondary endpoint was to quantify the morbidity of OPS and identify predictive factors for wound complications. RESULTS: Of 211 patients, 89 (42.2%) had a flap reconstruction. Surgery was realized on an irradiated field in 56 (62.9%) patients. Without OPS, all patients were candidates either for amputation (n = 9,10.1%) due to vessels/nerve infiltration, or R1/R2 resection (n = 80,89.9%). Seventy-two (80.0%) pedicle flaps and 18 (20.0%) free flaps were used. No R2 resections were performed. R0 and R1 margins were achieved in 82 (92.1%) and 7 (7.9%), respectively. The median closest margin was 3 mm (IQR 1-6 mm). Among R1 patients, 5 had positive margins along a preserved critical structure, 2 patients had well-differentiated liposarcomas. The surgical morbidity rate was 33.3% (30/90 flaps). The reoperation rate was 15.7% (14/89 patients). CONCLUSIONS: In a referral sarcoma center, the collaboration between the surgical oncologist and the plastic surgery team should be considered upfront in the surgical plan, allowing the most adequate wide oncological resection with acceptable postoperative morbidity.

Pleuropulmonary blastoma in children and adolescents: The EXPeRT/PARTNER diagnostic and therapeutic recommendations.

Pleuropulmonary blastoma (PPB) is a rare cancer occurring mainly during early childhood and often associated with germline DICER1 mutations. It is classified by the macroscopic appearance into three interrelated clinico-pathologic entities on a developmental continuum. Complete tumor resection is a main prognostic factor and can be performed at diagnosis or after neoadjuvant treatment that includes chemotherapy and in some cases radiotherapy. Optimal modalities of neo- or adjuvant treatments can be challenging taking into account potential long-term toxicities in this young population. This paper presents the recommendations for diagnosis and treatment of children and adolescents with PPB elaborated by the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) within the European Union-funded project PARTNER (Paediatric Rare Tumours Network - European Registry).

Pattern of relapse in pediatric localized extremity rhabdomyosarcomas correlated with locoregional therapies administered.

BACKGROUND: Treatment of extremity rhabdomyosarcomas (RMS) includes chemotherapy, surgery, and radiotherapy. Lymph node irradiation is recommended in the presence of regional node involvement at diagnosis. The aim of this study was to analyze the correlation between the pattern of relapse of non-metastatic extremity RMS and the initial therapies delivered. METHODS: All patients with localized extremity RMS prospectively treated in France in the MMT-95 and RMS-05 protocols were selected. Extent of disease and pattern of relapse were evaluated by clinical examination and imaging. RESULTS: We identified 59 patients with clinical characteristics corresponding to unfavorable prognostic factors. Twenty patients (34%) were considered to have lymph node involvement at diagnosis. Regional node biopsy was performed in 32 patients (54%) and modified the lymph node stage in 8 of the 59 patients (14%). Seventy-three percent of patients received radiotherapy. Fifty-two patients achieved first remission. Overall, 26 patients underwent complete tumor resection, 17 had R1 margins, and 5 were not operated due to early tumor progression. With a median follow-up of 82 months (range: 5-287), 18 relapses had occurred, at least locoregional in 12 cases. The 5­year local and nodal control rates were 73% (63-86%) and 86% (77-95%), respectively. Five-year progression-free and overall survival were 57% (95%CI [45-72%]) and 70% (95%CI [58-84%]), respectively. CONCLUSION: The main sites of extremity RMS relapse are locoregional. Nodal failures in non-irradiated fields are not uncommon. We recommend systematic biopsy of in-transit nodes, especially in alveolar RMS and/or RMS with regional positive nodes at diagnosis to ensure their negativity.

Head and neck tumors in children and adolescents: Impact of a multidisciplinary tumor board.

INTRODUCTION: Cancer treatment in France is based on Multidisciplinary Tumor Board (MTB). In the Ile-de-France region (IDF), which includes 12 million inhabitants from Paris and the surrounding area, pediatric tumors of head and neck are discussed since 2013 in a dedicated Interregional Pediatric Multicentric MTB (IPMTB). The purpose of this study is to analyze the impact of the IDF head and neck IPMTB on the management of these tumors, 5 years after their implementation. MATERIALS AND METHODS: Retrospective study of all patient files presented in the IPMTB for a benign or malignant head-and-neck tumor, between 2013 and 2018. RESULTS: A total of 679 discussions were analyzed representing 428 patients. Median age was 7.5 years (range: 0-31 years). Malignant tumors represented 71% of cases, including 36% of rhabdomyosarcoma. Overall, 12% percent of the cases discussed came from centers outside of IDF. All meetings complied with multidisciplinary criteria required by French law. Proposals made during the IPMTB were followed in 86% of cases. Among the 251 proposals made by the referring teams prior to the IPMTB, 29% were secondarily modified after being discussed in the IPMTB. CONCLUSION: Thanks to their multidisciplinarity, high number of cases discussed and usual respect of their proposals, the IPMTB have made it possible to improve the coordination between all specialties involved in the patient's management, to apply the most recent and scientifically validated protocols, and to share the knowledge of different teams concerning the management of particularly rare tumors.

Second-line therapy in young patients with relapsed or refractory orbital rhabdomyosarcoma.

OBJECTIVE: Localized orbital rhabdomyosarcoma (oRMS) has an overall favourable prognosis with more than 90% of survival. Little is known about the best strategy in recurrent/refractory (R/R) cases. The purpose is to examine the characteristics of patients with R/R-oRMS, focusing on local therapy. METHODS: This is bicentric retrospective study. Analysis is of young patients (<30 years) with R/R-oRMS who were treated from 1989 to 2018 at the Institut Curie and Gustave Roussy Cancer Campus, France. RESULTS: Twenty-seven out of 162 patients (17%) with oRMS presented with R/R disease. 6 of these patients had alveolar RMS (22%), 3 of whom had initial parameningeal extension (11%). During first-line treatment, 18 patients (67%) had orbital radiotherapy. Median age at R/R was 10 years (ranges: 4-28) after a delay of 19 months from diagnosis (ranges: 3-40). Tumoral events were local relapses (22 cases), local progression (3 cases) or regional relapses (2 cases). Second-line treatments included chemotherapy (27 cases), radiotherapy (16 cases), surgery (exenteration; 8 cases) and metastasis/ nodal removal (3 cases). After a median follow-up of 99 months (range: 10-306), 4 patients died and 23 are in complete remission (CR) without treatment. One patient had subsequent relapse treated with exenteration and brachytherapy until a new tumour remission. Five-year event-free and overall survivals after first tumour event are, respectively, 84.4% (95% confidence interval: 71.5%-98.8%) and 85.8% (95% confidence interval: 72.1%-100.0%) CONCLUSION: R/R-oRMS is a rare situation. Second-line therapy is efficient in this location, sometime at the cost of lifesaving mutilating surgery. Second-line local therapy needs therefore to consider local radiotherapy if possible or complete wide surgery.

Locoregional Control and Survival in Children, Adolescents, and Young Adults With Localized Head and Neck Alveolar Rhabdomyosarcoma-The French Experience.

INTRODUCTION: The head and neck (HN) are the most frequent sites of pediatric rhabdomyosarcoma (RMS). Alveolar RMS (ARMS) represents ~20% of all RMS cases and frequently spread to lymph nodes (LNs). The aim was to report locoregional control, event-free survival (EFS), and overall survival (OS), according to clinical and pathological features, LN staging, and treatment modalities. METHODS: The study included all patients prospectively enrolled in EpSSG RMS 2005 study under 21 years of age with localized HN ARMS and diagnosed between 2005 and 2016 in France. Medical data including imaging, surgical report, and radiation therapy planes were analyzed. RESULTS: Forty-eight patients (median age 6 years; range 4 months-21 years), corresponding to 30 parameningeal and 18 non-parameningeal ARMS, were included. There were 33 boys (69%). Tumor locations included the following: orbit (n = 7) among which four cases had bone erosion, paranasal sinuses and nasal cavity (n = 16), deep facial spaces (n = 10), nasolabial fold (n = 8), and other non-parameningeal HN sites (n = 7). A fusion transcript of PAX3-FOXO1 or PAX7-FOXO1 was expressed in 33 of the 45 cases (73%) with molecular analysis. At diagnosis, 10 patients had primary resection of the primary tumor (PRPT) (none with microscopic complete resection) and 9 had LN staging. After induction chemotherapy, 26 patients (54%) had secondary resection of the primary tumor (SRPT) and 13 patients (27%) had cervical LN dissection. A total of 43 patients (90%) were treated with radiation therapy.With a median follow-up of 7 years (range 2-13 years), 5-year OS and EFS were 78% (95% CI, 63-88%) and 66% (95% CI, 51-78%), respectively. We observed 16 events (10 deaths): 4 local, 4 regional, 1 local and regional, and 7 metastatic. In univariate analysis, OS was only superior for patients under 10 years of age (p = 0.002), while FOXO1-negative ARMS, SRPT for parameningeal ARMS, and LN surgery were associated with significantly better EFS. CONCLUSION: Our study confirms a better outcome for fusion-negative ARMS and ARMS in children under 10 years. Moreover, LN surgery and SRPT of parameningeal tumor may improve EFS of ARMS. Larger studies are needed to confirm our findings.

High-dose proton therapy and tomotherapy for the treatment of sacral chordoma: a retrospective monocentric study.

OBJECTIVE: Radiation therapy (RT) is used for the treatment of sacral chordoma, in combination with surgery or alone for unresected tumours, to improve local control (LC) and potentially overall survival (OS). The purpose of the present study was to evaluate efficacy and toxicity of proton therapy (PT), and/or intensity modulated radiation therapy (IMRT), particularly Tomotherapy, for sacral chordoma treatment. Material: Between November 2005 and June 2018, 41 consecutive patients who were not included in clinical trials, received sacral chordoma radiation treatment in Institut Curie with Tomotherapy alone in 13 patients, and combined PT and Tomotherapy boost (Proton - Tomo) in 28 patients. RT was delivered as the exclusive local treatment in 11 patients, and as a post-operative complementary treatment in 30 patients. RESULTS: After a median follow-up of 46 months (range, 0-125 months), eight local relapses were observed, and seven patients developed distant metastasis (particularly bone and lung). The 2- and 5- year local relapse rates were 11.4% CI (0.65-22.2%) and 29% (10.5-47.4%), respectively. Over the follow-up period, ten patients died (24.4%). The estimated 2- and 5-year OS rates were 91.4% CI (82.5-100%) and 74.5% (59.4-93.5%), respectively. Fibrosis, cauda equina syndrome, and pain were the most common late toxicities. The comparison between Tomotherapy alone and Proton - Tomo revealed that acute and late cystitis were significantly more frequent in the Tomotherapy group: SHR = 0.12 IC95% (0.01-0.90 [p = .04]), as well as late proctitis. A dosimetric comparison confirmed the interest of PT to spare rectum and bladder in this context. CONCLUSION: RT remains essential to improve local control in sacral chordoma. The combination of proton and photon seems to improve organ at risk sparing, resulting in a decreased rate of reported late toxicities.