Safety of concurrent adjuvant radiotherapy and chemotherapy for locally advanced soft tissue sarcoma

2018 ◽  
Vol 104 (5) ◽  
pp. 322-329 ◽  
Author(s):  
Daniela Greto ◽  
Mauro Loi ◽  
Calogero Saieva ◽  
Cristina Muntoni ◽  
Camilla Delli Paoli ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Locally Advanced ◽  
Radiation Therapy Oncology Group ◽  
European Organization ◽  
Free Survival ◽  
Radiotherapy Toxicity

Introduction: This retrospective study analyzes the safety and feasibility of concurrent chemoradiotherapy (CRT) in adjuvant treatment of soft tissue sarcoma (STS). Methods: A total of 158 patients with STS were retrospectively analyzed. Anthracycline-based computed tomography was performed in high-risk patients. Acute radiotherapy toxicity and chemotherapy-related toxicity were assessed according to the Common Terminology Criteria for Adverse Events 4.0; late radiotherapy toxicity was recorded according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria. Results: Fifty-four (34.2%) patients received CRT. Mean follow up was 5.4 years (range .2–21.1 years). Local DFS–recurrence-free survival, distant DFS–relapse-free survival, and overall survival were 79.1%, 76.4%, and 64.6%, respectively, at last follow-up. Leukopenia occurred in 11.4% of patients. Skin acute toxicity developed in 60.1% of patients and determined interruption of radiotherapy treatment in 19 (12%) patients. Nineteen patients (12%) experienced moderate fibrosis (grade 2). Mild and moderate joint stiffness was recorded in 16 (10.1%) patients. Size ≥5 cm was the only predictor of local recurrence at multivariate analysis (hazard ratio [HR] 9.65, 95% confidence interval [CI] 1.28–72.83, p = .028). Age and stage resulted as independent distant relapse predictors (HR 4.77, 95% CI 1.81–12.58, p = .002 and HR 4.83, CI 1.41–16.57, p = .012, respectively). At Cox regression univariate analysis, Karnofsky Performance Status, size, and stage were significant survival predictors (HR 2.23, 95% CI 1.02–4.87, p = .045; HR 2.88, 95% CI 1.10–7.52, p = .031; HR 2.59, 95% CI 1.11–6.04, p = .028). Conclusions: Concurrent CRT is a well-tolerated treatment option with no additional toxicity compared to exclusive radiotherapy or sequential CRT.

scholarly journals Stereotactic Body Radiotherapy for Metastatic and Recurrent Soft Tissue Sarcoma

2020 ◽  
Author(s):  
Xiaoyao Feng ◽  
Jing Li ◽  
Aomei Li ◽  
Han Zhou ◽  
Xixu Zhu ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Survival Rates ◽  
Progression Free Survival ◽  
Hematogenous Metastasis ◽  
Invasive Growth ◽  
Free Survival ◽  
Grade 3 ◽  
Clinical Transformation

Abstract BackgroundSoft tissue sarcoma（STS） is a malignant tumor of highly heterogeneous mesenchymal origin. STS has a biologic pattern and clinical transformation with localized invasive growth and susceptibility to hematogenous metastasis. Metastatic and recurrent soft tissue sarcoma may be treated by local therapeutic options, including surgery and radiation therapy. This study evaluated the safety and efficacy of SBRT for metastatic and recurrent soft tissue sarcoma.MethodsWe performed a retrospective analysis of 37 STS patients with 58 lesions treated with SBRT from 2009-2019 at our institution. We analyze the local control (LC), overall survival (OS), progression free survival (PFS) and toxicity rates of the patients.ResultThe median follow-up was 20 months（range 2 to 120 months）. One and two year LC rates were 75.3% and 55.2% [95% confidence interval (CI) 20–25 months]. Median OS was 24 months and the survival rates were 66.6%, 45% and 26.6% at 1, 2 and 3-year after SBRT. Median PFS were 11months (95% CI 8–18 months). No acute or chronic grade ≥ 3 toxicity was observed.ConclusionsIn patients with metastatic and recurrent STS, LC, OS and PFS were higher than expected. SBRT should be a proper treatment option for STS.

Randomized Phase II Study of Docetaxel Versus Doxorubicin in First- and Second-Line Chemotherapy for Locally Advanced or Metastatic Soft Tissue Sarcomas in Adults: A Study of the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group

2000 ◽  
Vol 18 (10) ◽  
pp. 2081-2086 ◽  
Author(s):  
Jaap Verweij ◽  
Siow Ming Lee ◽  
Wlodzimir Ruka ◽  
Jose Buesa ◽  
Robert Coleman ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Locally Advanced ◽  
Soft Tissue Sarcomas ◽  
Bone Sarcoma ◽  
Phase Iii ◽  
European Organization ◽  
Randomized Phase Ii ◽  
Docetaxel Treatment ◽  
Phase Iii Study

PURPOSE: To assess antitumor response and time to progression (TTP) with docetaxel compared with doxorubicin in first-line treatment of advanced and/or metastatic soft tissue sarcoma. PATIENTS AND METHODS: Patients with measurable soft tissue sarcoma lesions and adequate bone marrow, liver, and renal function were entered onto the study. They were randomized to either docetaxel 100 mg/m2 given as a 1-hour intravenous infusion every 3 weeks or doxorubicin 75 mg/m2 given as a bolus injection every 3 weeks. A maximum of seven cycles of treatment were scheduled. The study was designed as a randomized phase III study evaluating TTP by log-rank model. There was a clause for premature closure of the trial if fewer than five responses were observed among the first 25 assessable patients in the docetaxel treatment arm. RESULTS: Eighty-six patients were entered onto the study; 85 were assessable for toxicity and 83 for response. The rate of severe granulocytopenia was not significantly different between the two arms. Nausea (P = .001), vomiting (P < .001), and stomatitis (P = .005) were more common with doxorubicin therapy, whereas neurotoxicity was more frequent with docetaxel treatment. The response rate to doxorubicin therapy was 30% (95% confidence interval, 17% to 46%), whereas no responses to docetaxel therapy were seen (P < .001). In view of this, the trial was closed prematurely and the phase III study part was not conducted. CONCLUSION: Docetaxel is inactive in soft tissue sarcomas and cannot be recommended for further use in treatment of this disease.

Dactinomycin (A) and vincristine (V) with or without cyclophosphamide (C) and radiation therapy (RT) for newly diagnosed patients with low-risk embryonal/botryoid rhabdomyosarcoma (RMS). An IRS-V report from the Soft Tissue Sarcoma Committee of the Children’s Oncology Group (STS COG)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 9001-9001 ◽  
Author(s):  
D. O. Walterhouse ◽  
J. L. Meza ◽  
R. B. Raney ◽  
J. Anderson ◽  
E. S. Wiener ◽  
...  
Keyword(s):  
Overall Survival ◽  
Radiation Therapy ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Primary Endpoint ◽  
Low Risk ◽  
Newly Diagnosed ◽  
Oncology Group ◽  
Free Survival

9001 Background: The STS COG defines patients with low-risk RMS as those with localized tumors of embryonal histology that occur in favorable sites or occur in unfavorable sites and are grossly resected. Intergroup Rhabdomyosarcoma Studies (IRS)-III (1984–1991) and -IV (1991–1997) found that these patients had a 5-year failure-free survival (FFS) of 83% and an overall survival of 95%. Methods: Two subsets were identified for the IRS-V low-risk RMS study (D9602) (1997–2004) based on the hypothesis that they required different treatment intensities to achieve similar excellent outcomes. Patients assigned to Subset A (Stage [Sg] 1 Group [Gp] I/IIA, Sg 1 Gp III orbit, Sg 2 Gp I) received VA (cumulative doses over 1 year of treatment: V: 54 mg/m2, A: 24 mg/kg) ± local RT. Patients assigned to Subset B (Sg 2 Gp IIB/C, Sg 1 Gp III non-orbit, Sg 2 Gp II, Sg 3 Gp I/II) received VA + C (C: 28.6 g/m2) ± RT. The RT dose was reduced to 36 Gy (instead of 41.4 Gy on IRS-IV) for Gp IIA patients and to 45 Gy (instead of 50.4 or 59.4 Gy on IRS-IV) for Gp III orbit patients. The primary endpoint was FFS. Results: Estimated 3-yr FFS was 89% (95% CI 84%, 93%) for Subset A (n=263) and 89% (95% CI 77%, 95%) for Subset B (n=79). Median follow-up was 2.9 years. Estimated 3-yr FFS was 80% (95% CI 64%, 89%; n=59) for patients with Sg 1 Gp IIA disease and 88% (95% CI 77%, 94%; n=76) for Gp III orbit disease. Conclusions: There is not evidence to suggest that outcome for these patients differs from outcomes observed in similar patients treated on IRS-III and IRS-IV. No significant financial relationships to disclose.

Cisplatin (C) based chemoradiation (CXRT) for locally advanced squamous cell carcinoma (SCCA) of the anal canal (AC): A 20-year perspective.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 482-482 ◽  
Author(s):  
C. Eng ◽  
Y. Xing ◽  
Y. N. You ◽  
G. J. Chang ◽  
P. Das ◽  
...  
Keyword(s):  
Anal Canal ◽  
Salvage Surgery ◽  
Univariate Analysis ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Rank Test ◽  
Free Survival ◽  
Phase Iii Studies

482 Background: The standard of care for locally advanced SCCA of the AC is 5-fluorouracil (5-FU)/mitomycin C (MMC) with concurrent XRT. C was evaluated with 5-FU in 2 large phase III studies (RTOG 98-11 and ACT II) to establish superiority over 5-FU/MMC. Neither study showed significant differences for disease-free survival (DFS) or overall survival (OS). RTOG 98-11 reported reduced colostomy-free survival (CFS) in the C-induction arm; no differences were noted in the ACT II study. We present our 20-year experience with C for locally advanced SCCA of the AC which has been adopted as the standard unless contraindicated. Methods: A retrospective, single institution analysis for locally advanced SCCA of the AC was completed in patients (pts) that received concurrent 5-FU/C/XRT from 1989-2009. Medical records were reviewed for history of STDs, chronic immunosuppression, stage, dose of XRT, toxicity, clinical response (CR), recurrence, and OS. Multidisciplinary management included surgical, radiation, and medical oncologists. OS, DFS, and CFS were calculated using the K-M method. The log-rank test was used to compare OS among these subgroups. Results: 185 pts were identified (51 M:134 F). The median age was 56 (35-83 y.o.). AJCC stage was I (n = 25); II (n = 76); IIIA (n = 36); and IIIB (n = 48). The median XRT dose was 55 Gy in 30 fractions. 181 pts were evaluable for response; 4 were lost to follow up. Complete CR (cCR) was noted in 169 pts (93%); partial response (n = 12); 6 pts received an APR. After a median follow up of 8.6 years, 14 pts (8%) developed local recurrence; 11 received salvage surgery. 16 pts (9%) developed distant metastases (DM). The 5-yr DFS = 81%, 5-yr OS = 85% and 5-yr CFS was 88%. By univariate analysis, N-stage was a poor prognostic indicator for 5-yr DFS (p = 0.02) and DM (p = 0.046) but not OS or CFS. Increased T-stage correlated with salvage surgery (p = 0.005). Conclusions: Cisplatin-based chemoradiation for locally advanced SCCA of the anal canal resulted in favorable DFS, OS, and CFS compared to historical data and phase III studies. Platinum-based therapy for anal cancer appears to be an acceptable alternative to MMC and should be considered as a standard option for locally advanced disease. No significant financial relationships to disclose.

Limb preserving surgery for soft-tissue sarcoma in the hand: a retrospective study of 51 cases

2020 ◽  
Vol 45 (6) ◽  
pp. 629-635 ◽  
Author(s):  
Mehran Dadras ◽  
Hans-Ulrich Steinau ◽  
Ole Goertz ◽  
Marcus Lehnhardt ◽  
Björn Behr ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Soft Tissue ◽  
Local Recurrence ◽  
Soft Tissue Sarcoma ◽  
Tumour Size ◽  
Long Term Results ◽  
Resection Margins ◽  
Incomplete Resection ◽  
Free Survival

Our retrospective study analysed the long-term results of a conservative limb-preserving surgical strategy in 51 patients with soft-tissue sarcoma of the hand from a single institution. We assessed survival and prognostic factors, including the surgical margins. No transradial amputations were performed. Microscopically free resection margins were obtained in 45 of the patients. The remaining six patients had microscopically incomplete resection. Forty-four surviving patients had a median follow-up of 6.5 years (range 12–307), and one patient had no follow-up beyond 3 months following surgery. Among those patients, 29 had more than 5 years of follow-up. Five-year local-recurrence-free survival was 65%, metastasis-free survival was 84%, and disease-specific survival was 91%. Tumour size was predictive of all outcome parameters, but positive resection margins adversely affected local recurrence only. Survival was similar to the survival after a more radical surgical approach reported in the literature. Level of evidence: IV

scholarly journals Preoperative accelerated radiotherapy combined with chemotherapy in a defined cohort of patients with high risk soft tissue sarcoma: a Scandinavian Sarcoma Group study

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Kirsten Sundby Hall ◽  
Øyvind S. Bruland ◽  
Bodil Bjerkehagen ◽  
Elisabet Lidbrink ◽  
Nina Jebsen ◽  
...  
Keyword(s):  
High Risk ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Local Control ◽  
Survival Data ◽  
Locally Advanced ◽  
Resection Margins ◽  
Accelerated Radiotherapy ◽  
Group B

Abstract Background We recently reported outcomes from a Scandinavian Sarcoma Group adjuvant study (SSG XX group A) conducted on localized and operable high risk soft tissue sarcoma (STS) of the extremities and trunk wall. SSG XX, group B, comprised of patients in a defined cohort with locally advanced STS considered at high risk for intralesional surgery. These patients received preoperative accelerated radiotherapy, together with neoadjuvant and adjuvant chemotherapy. Herein we report the results of this group B. Methods Twenty patients with high-grade, locally advanced and deep STS located in lower extremities (n = 12), upper extremities (5) or trunk wall (3) were included. The median age was 59 years and 14 patients were males. The treatment regimen consisted of 6 cycles of doxorubicin (60 mg/m2) and ifosfamide (6 g/m2), with three cycles given neoadjuvantly, and preoperative radiotherapy (1, 8 Gyx2/daily to 36 Gy) between cycles 2 and 3. After a repeated MRI surgery was then conducted, and the remaining 3 chemotherapy cycles were given postoperatively at 3 weeks intervals. Survival data, local control, toxicity of chemotherapy and postoperative complications are presented. Results Median follow-up time for metastasis-free survival (MFS) was 2.8 years (range 0.3–10.4). The 5-year MFS was 49.5% (95% confidence interval [CI] 31.7–77.4). The median follow-up time was 5.4 years (range 0.3–10.4) for overall survival (OS). The 5-year OS was 64.0% (95% CI 45.8–89.4). The median tumour size was 13 cm, with undifferentiated pleomorphic sarcoma (n = 10) and synovial sarcoma (n = 6) diagnosed most frequently. All patients completed surgery. Resection margins were R0 in 19 patients and R1 in 1 patient. No patients had evidence of disease progression preoperatively. Three patients experienced a local recurrence, in 2 after lung metastases had already been diagnosed. Eleven patients (55%) had postoperative wound problems (temporary in 8 and persistent in 3). Conclusions Preoperative chemotherapy and radiotherapy were associated with temporary wound-healing problems. Survival outcomes, local control and toxicities were deemed satisfactory when considering the locally advanced sarcoma disease status at primary diagnosis. Trial registration This study was registered at ClinicalTrials.gov Identifier NCT00790244 and with European Union Drug Regulating Authorities Clinical Trials No. EUDRACT 2007-001152-39

scholarly journals Expression of IL4Rα and IL13Rα1 Are Associated With Poor Prognosis of Soft-tissue Sarcoma of the Extremities, Superficial Trunk, and Retroperitoneum 

2020 ◽  
Author(s):  
Kyoung Min Kim ◽  
Usama Khamis Hussein ◽  
See-Hyoung Park ◽  
Young Jae Moon ◽  
Zhongkai Zhang ◽  
...  
Keyword(s):  
Overall Survival ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Cancer Progression ◽  
Univariate Analysis ◽  
Soft Tissue Sarcomas ◽  
Prognostic Indicators ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Human Soft Tissue

Abstract BackgroundIL4Rα and IL13Rα1 are constituents of the type II IL4 receptor. Recently, IL4Rα and IL13Rα1 were reported to have roles in cancer progression and suggested as potential prognostic markers. However, studies on IL4Rα and IL13Rα1 in soft-tissue sarcomas have been limited. MethodsThis study investigated the expression of IL4Rα and IL13Rα1 in 89 soft-tissue sarcomas of the extremities, superficial trunk, and retroperitoneum. ResultsIn human soft-tissue sarcomas, immunohistochemical expression of IL4Rα was significantly associated with IL13Rα1 expression. Nuclear and cytoplasmic expression of IL4Rα and IL13Rα1 were significantly associated with shorter survival of soft-tissue sarcoma patients in univariate analysis. Multivariate analysis indicated that nuclear expression of IL4Rα and IL13Rα1 were independent indicators of shorter overall survival (IL4Rα; p = 0.002, IL13Rα1; p = 0.016) and relapse-free survival (IL4Rα; p = 0.022, IL13Rα1; p < 0.001) of soft-tissue sarcoma patients. Moreover, the co-expression pattern of nuclear IL4Rα and IL13Rα1 was an independent indicator of shorter survival of soft-tissue sarcoma patients (overall survival; overall p < 0.001, relapse-free survival; overall p < 0.001). ConclusionsThis study suggests IL4Rα and IL13Rα1 are associated with the progression of soft-tissue sarcoma, and the expression of IL4Rα and IL13Rα1 might be novel prognostic indicators of soft-tissue sarcoma patients.

Impact of leucocyte modifications in patients with locally advanced cervical treated by chemoradiotherapy.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e18014-e18014
Author(s):  
Christine Gennigens ◽  
Marjolein de Cuypere ◽  
Annelore Barbeaux ◽  
Frederic Forget ◽  
Johanne Hermesse ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Cox Regression ◽  
External Beam Radiotherapy ◽  
Linear Regression Analysis ◽  
Univariate Analysis ◽  
Locally Advanced ◽  
White Blood Cells ◽  
Polymorphonuclear Neutrophils ◽  
The Impact

e18014 Background: Concomitant cisplatin-based chemoradiotherapy (CCRT), followed by image guided-adaptive brachytherapy (IGABT) is the recommended treatment for patients suffering from locally advanced cervical cancer (LACC). Methods: Between January 2010 and May 2017, 103 patients with LACC (FIGO 2009-stages IB2-IVA) received CCRT followed by IGABT. The objectives of this study were to evaluate the impact of white blood cells (WBC) and polymorphonuclear neutrophils (PMN) counts variations on outcomes. This variable was calculated by substraction between WBC or PMN levels at the first cycle (CB) and the last cycle (CL) of chemotherapy (CT)(DCB-CL). The data were reviewed retrospectively, with Cox regression for univariate and multivariate analysis. Results: The median age at diagnosis was 50 years. The median tumor size at diagnosis was 47mm. The majority of the patients had FIGO stage II (60.2%) or stage I (21.4%) disease with squamous histology (88.3%). Patients received a median dose of external-beam radiotherapy (EBRT) of 45 Gy (range 40-50.4 Gy) by 1.8-2 Gy fractions, with a median cumulative dose of all the radiotherapy of 85 Gy. The median duration of EBRT+IGABT was 51 days (range 31-94). All patients received at least one cycle of cisplatin, but the majority received 5 (40.4%) or 6 (39.4%) cycles. The median follow-up time for all patients was 30.1 months. The overall survival (OS) and recurrence-free survival (RFS) at 3 years was 81,4% and 76,8% respectively. Univariate analysis associated higher DCB-CL WBC and DCB-CL PMN with better OS and RFS. Multivariate analysis confirmed that DCB-CL WBC (HR, 0.856; 95% CI, 0.737-0.986; p = 0.018) and DCB-CL PMN (HR, 0.863; 95% CI, 0.750-0.994; p = 0.041) were associated with better OS and RFS respectively. A linear regression analysis was performed to cross the DCB-CL WBC/PMN and the number of CT cycles. This analysis reveals that an increasing number of CT cycles is linked to an increased DCB-CL WBC/PMN. Conclusions: Our study reveals the impact of DCB-CL WBC and PMN on outcomes. These two tests could become biomarkers during CCRT to discuss adjuvant treatments, but also to adapt our follow-up.

The role of ifosfamide-doxorubicin chemotherapy in the treatment histology-specific, high grade, locally advanced soft tissue sarcoma: A 14-year experience.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e23529-e23529
Author(s):  
Barry W Goy
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Locally Advanced ◽  
Local Therapy ◽  
Synovial Cell ◽  
Favorable Effect ◽  
High Grade ◽  
Undifferentiated Sarcoma ◽  
Free Survival ◽  
Prognostic Features

e23529 Background: To compare long-term outcomes of high grade, locally advanced, primary soft tissue sarcoma (STS), using Ifosfamide-Doxorubicin vs local therapy alone, in histology-specific sarcomas. Methods: Retrospective analysis was performed on 127 patients from 2005 to 2018, who had STS of extremity or trunk, > 5cm, that were either Synovial Cell, Dedifferentiated Liposarcoma (DDL), Myxofibrosarcoma, Round Cell Liposarcoma (RCLS), Undifferentiated Pleomorphic Sarcoma (UPS), or Undifferentiated Sarcoma not otherwise specified (NOS), with central pathology review. Ifosfamide-doxorubicin was generally given neoadjuvant, followed by radiation and wide excision, with chemotherapy given in 38 patients, while 89 received local therapy alone. Multi-variable analysis of prognostic factors was performed, and local-recurrence-free-survival (LRFS), distant-metastases-free-survival (DMFS), disease-specific-survival (DSS), and overall-survival(OS) were estimated using Kaplan-Meier. Results: Median follow-up was 4.5 years. Younger age (p < 0.0001) and Synovial histology (p = 0.0002) had significantly higher rates of receiving chemotherapy. Size > 10cm and trunk location were poor prognostic features on multivariable analysis (MVA) affecting DMFS, DSS, and OS, while DDL histology had a more favorable effect; although size, trunk location, and DDL histology were not significantly different between treatment groups. Ifosfamide-Doxorubicin vs local therapy alone improved 5-year DMFS at 70.2% vs 49.5% ,p = 0.02, DSS 83.5% vs 57.9%, p = 0.009, and OS 80.6% vs 53.8%, p = 0.002. Sub-analysis of non-synovial histologies still showed a significant improvements in favor of chemotherapy in DMFS,(p = 0.04), DSS (p = 0.02), and OS (p = 0.003). Conclusions: Ifosfamide-Doxorubicin chemotherapy benefits younger patients with > 5cm, high grade, STS of the trunk or extremity, with histologies of Synovial Cell, DDL, Myxofibrosarcoma, RCLS, UPS, or Undifferentiated Sarcoma NOS.

Long-term evaluation of the novel radioenhancer NBTXR3 plus radiotherapy in patients with locally advanced soft tissue sarcoma treated in the phase II/III Act.In.Sarc trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 11544-11544
Author(s):  
Sylvie Bonvalot ◽  
Piotr Rutkowski ◽  
Juliette Thariat ◽  
Sebastien Carrère ◽  
Anne Ducassou ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Functional Outcome ◽  
Locally Advanced ◽  
Intratumoral Injection ◽  
Post Treatment ◽  
Preoperative Treatment ◽  
Advanced Soft Tissue Sarcoma

11544 Background: NBTXR3, a novel radioenhancer activated by radiotherapy (RT) demonstrated superior efficacy, as preoperative treatment, in patients with locally advanced soft tissue sarcoma (LA STS), compared to RT alone. Primary endpoint of pCR rate was 16% vs 8% (p=0.044) and R0 margin rate was 77% vs 64% (p=0.042) (Bonvalot et al. Lancet Oncol. 2019). No modification of the early safety profile of RT was observed, leading to market authorization. Here we report on the long-term safety, limb function and quality of life. Methods: This phase II/III randomized (1:1), international trial included adult patients with LA STS of the extremity or trunk wall, requiring preoperative RT (NCT02379845). Patients were treated with either a single intratumoral injection of NBTXR3 (volume equivalent to 10% of tumor volume, at 53.3g/L) plus EBRT (arm A), or EBRT alone (arm B) (50 Gy in 25 fractions), followed by surgery. The primary and main secondary efficacy endpoints were previously reported. Safety of NBTXR3+RT, as preoperative treatment, was evaluated as secondary endpoint. We present the safety analyses done in the “all treated population”, with data recorded during at least a two-year follow-up. Important parameters related to HR-QoL, including functional outcome were studied using the EQ-5D, RNLI, TESS and MSTS questionnaires. Results: Patients had at least two-year follow-up and the lost to follow-up rate was very low (1.9%). RT-related SAEs were observed in 11.2% (10/89) vs 13.3% (12/90) in A vs B. Post-treatment AEs, any grade, were observed in 51.7% (46/89) vs 57.8% (52/90) and serious post-treatment AEs in 13.5% (12/89) vs 24.4% (22/90) of patients in A vs B. Second primary cancer was observed in 1 patient in arm A and 6 patients in arm B. Long-term safety continues to demonstrate that NBTXR3 plus RT has no impact on post-surgical wound complications (24.7% vs 36.7%, A vs B). Furthermore, the evaluation of radiation late toxicities in limbs such as fibrosis (4.5% vs 7.7%), arthrosis (2.2% vs 0.0%) and edema (6.7% vs 2.2%) that may alter limb function showed no difference between arms. Accordingly, HR-QoL evaluation yielded no difference in functional outcome. In addition, the intratumoral injection of NBTXR3 did not induce cancer cell seeding at the former tumor site. Finally, sequelae or chronic tissue disturbances at the former tumor localization were similar in both treatment arms, confirming that the increase of energy dose deposit and the physical presence of NBTXR3 did not impact post-treatment limb functions. Conclusions: The long-term safety results demonstrate that the addition of NBTXR3 to EBRT neither added toxicity nor modified the bystander effect of RT. The results presented here associated with the efficacy data reported previously reinforce the favorable benefit-risk ratio of the use of NBTXR3 in patients with LA STS. Clinical trial information: NCT02379845.

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