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2021 – Eur J Surg Oncol – STS Retrospective Study

nano-pub — Fri, 12 Mar 2021 11:49:27 +0000

Authors

Sylvie Bonvalot1, Jay Wunder2, Alessandro Gronchi3, Javier Martin Broto4, Robert Turcotte5, Marco Rastrelli6, Zsuzsanna Papai7, Stefano Radaelli3, Lars H. Lindner8, Felix Shumelinsky9, Antonio Cubillo10, Piotr Rutkowski11, Clementine Demaire12, Danielle Strens12, Georgi Nalbantov12

1 – Department of Surgery, Institut Curie, Paris University, Paris, France
2 – Department of Surgery, Sinai Health System, Toronto, Ontario, Canada
3 – Department of Surgery, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milan, Italy
4 – Department of Medical Oncology, Hospital Virgen Del Rocio, And Institute of Biomedicine of Sevilla (IBIS) (HUVR, CSIC, University of Sevilla), Sevilla, Spain
5 – Department of Surgery, McGill University Health Centre, Montreal, Quebec, Canada
6 – Department of Surgical Oncology, Istituto Oncologico Veneto, Padova, Italy
7 – Department of Oncology, Honved Hospital – Hungarian Defence Forces Military Hospital, Budapest, Hungary
8 – Department of Medicine III, University Hospital, LMU Munich, Munich, Germany
9 – Department of Surgery – Bone and Connective Tissue Tumour Surgery, Jules Bordet Institute, Brussels, Belgium
10 – Department of Medical Oncology, Hospital Universitario Sanchinarro, Centro Integral Oncologico Clara Campal HM CIOCC, Madrid, Spain
11 – Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland
12 – Health Economics & Outcome Research Team, Monitor Deloitte, Zaventem, Belgium

Summary

Background: Locally advanced soft tissue sarcoma (STS) management may include neoadjuvant or adjuvant treatment by radiotherapy (RT), chemotherapy (CT) or chemoradiotherapy (CRT) followed by wide surgical excision. While pathological complete response (pCR) to preoperative treatment is prognostic for survival in osteosarcomas, its significance for STS is unclear. We aimed to evaluate the prognostic significance of pCR to pre-operative treatment on 3-year disease-free survival (3y-DFS) in STS patients.

Methods: This is an observational, retrospective, international, study of adult patients with primary non-metastatic STS of the extremities and trunk wall, any grade, diagnosed between 2008 and 2012, treated with at least neoadjuvant treatment and surgical resection and observed for a minimum of 3 years after diagnosis. The primary objective was to evaluate the effect of pCR. (≤5% viable tumor cells or ≥95% necrosis/fibrosis) on 3y-DFS. Effect on local recurrence-free survival (LRFS), distant recurrence-free survival (MFS) overall survival (OS) at 3 years was also analyzed. Statistical univariate analysis utilized chi-square independence test and odds ratio confidence interval (CI) estimate, multivariate analysis was performed using LASSO.

Results: A total of 330 patients (median age 56 years old, range:19–95) treated by preoperative RT (67%), CT (15%) or CRT (18%) followed by surgery were included. pCR was achieved in 74/330 (22%) of patients, of which 56/74 (76%) had received RT. 3-yr DFS was observed in 76% of patients with pCR vs 61% without pCR (p < 0.001). Multivariate analysis showed that pCR is statistically associated with better MFS (95% CI, 1.054–3.417; p = 0.033), LRFS (95% CI, 1.226–5.916; p = 0.014), DFS (95% CI, 1.165–4.040; p = 0.015) and OS at 3 years (95% CI, 1.072–5.210; p = 0.033).

Conclusions: In a wide, heterogeneous STS population we showed that pCR to preoperative treatment is prognostic for survival.

The post 2021 – Eur J Surg Oncol – STS Retrospective Study first appeared on Nano Publications.

2019 – The Lancet Oncology – Act.In.Sarc

nano-pub — Mon, 02 Sep 2019 10:02:52 +0000

Authors

Sylvie Bonvalot, Piotr L Rutkowski, Juliette Thariat, Sébastien Carrère, Anne Ducassou, Marie-Pierre Sunyach, Peter Agoston, Angela Hong, Augustin Mervoyer, Marco Rastrelli, Victor Moreno, Rubi K Li, Béatrice Tiangco, Antonio Casado Herraez, Alessandro Gronchi, László Mangel, Teresa Sy-Ortin, Peter Hohenberger, Thierry de Baère, Axel Le Cesne, Sylvie Helfre, Esma Saada-Bouzid, Aneta Borkowska, Rodica Anghel, Ann Co, Michael Gebhart, Guy Kantor, Angel Montero, Herbert H Loong, Ramona Vergés, Lore Lapeire, Sorin Dema, Gabriel Kacso, Lyn Austen, Laurence Moureau-Zabotto, Vincent Servois, Eva Wardelmann, Philippe Terrier, Alexander J Lazar, Judith V M G Bovée, Cécile Le Péchoux, Zsusanna Papai

Summary

Background: Pathological complete response to preoperative treatment in adults with soft-tissue sarcoma can be achieved in only a few patients receiving radiotherapy. This phase 2–3 trial evaluated the safety and efficacy of the hafnium oxide (HfO2) nanoparticle NBTXR3 activated by radiotherapy versus radiotherapy alone as a pre-operative treatment in patients with locally advanced soft-tissue sarcoma.

Methods: Act.In.Sarc is a phase 2–3 randomised, multicentre, international trial. Adults (aged ≥18 years) with locally advanced soft-tissue sarcoma of the extremity or trunk wall, of any histological grade, and requiring preoperative radiotherapy were included. Patients had to have a WHO performance status of 0–2 and a life expectancy of at least 6 months. Patients were randomly assigned (1:1) by an interactive web response system to receive either NBTXR3 (volume corresponding to 10% of baseline tumour volume at a fixed concentration of 53·3g/L) as a single intratumoural administration before preoperative external-beam radiotherapy (50 Gy in 25 fractions) or radiotherapy alone, followed by surgery. Randomisation was stratified by histological subtype (myxoid liposarcoma vs others). This was an open-label study. The primary endpoint was the proportion of patients with a pathological complete response, assessed by a central pathology review board following European Organisation for Research and Treatment of Cancer guidelines in the intention-to-treat population full analysis set. Safety analyses were done in all patients who received at least one puncture and injection of NBTXR3 or at least one dose of radiotherapy. This study is registered with ClinicalTrials.gov, number NCT02379845, and is ongoing for long-term follow-up, but recruitment is complete.

Findings: Between March 3, 2015, and Nov 21, 2017, 180 eligible patients were enrolled and randomly assigned and 179 started treatment: 89 in the NBTXR3 plus radiotherapy group and 90 in the radiotherapy alone group.Two patients
in the NBTXR3 group and one patient in the radiotherapy group were excluded from the efficacy analysis because they were subsequently discovered to be ineligible; thus, a total of 176 patients were analysed for the primary endpoint in the intention-to-treat full analysis set (87 in the NBTXR3 group and 89 in the radiotherapy alone group). A pathological complete response was noted in 14 (16%) of 87 patients in the NBTXR3 group and seven (8%) of 89 in the radiotherapy alone group (p=0·044). In both treatment groups, the most common grade 3–4 reatment-emergent adverse event was postoperative wound complication (eight [9%] of 89 patients in the NBTXR3 group and eight [9%] of 90 in the radiotherapy alone group). The most common grade 3–4 adverse events related to NBTXR3 administration were
injection site pain (four [4%] of 89) and hypotension (four [4%]) and the most common grade 3–4 radiotherapy-related adverse event was radiation skin injury in both groups (five [6%] of 89 in the NBTXR3 group and four [4%] of 90 in the radiotherapy alone group). The most common treatment-emergent grade 3–4 adverse event related to NBTXR3 was hypotension (six [7%] of 89 patients). Serious adverse events were observed in 35 (39%) of 89 patients in the NBTXR3 group and 27 (30%) of 90 patients in the radiotherapy alone group. No treatment-related deaths occurred.

Interpretation: This trial validates the mode of action of this new class of radioenhancer, which potentially opens a large field of clinical applications in soft-tissue sarcoma and possibly other cancers.

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2016 – Phase I data NBTXR3 Soft Tissue Sarcoma – Bonvalot et al.

nano-pub — Mon, 06 Feb 2017 12:12:29 +0000

Authors

Sylvie Bonvalot1, Cecile Le Pechoux2, Thierry De Baere2, Guy Kantor3, Xavier Buy3, Eberhard Stoeckle3, Philippe Terrier2, Paul Sargos3, Jean Michel Coindre3, Nathalie Lassau2, Rafik Ait Sarkouh4, Mikaela Dimitriu4, Elsa Borghi4, Laurent Levy4, Eric Deutsch2, and Jean-Charles Soria2
Nanobiotix, 60 rue de wattignies, 75012 Paris, France

Summary

Purpose: This phase I study aimed to determine the recommended dose (RD), safety profile, and feasibility of a procedure combining intratumoral injection of hafnium oxide nanoparticles (NBTXR3; a radioenhancer) and external beam radiotherapy (EBRT) for preoperative treatment of adults with locally advanced soft tissue sarcoma (STS).

Experimental Design: Patients had a preoperative indication of EBRT for STS of the extremity or trunk. Baseline tumor volume (TV) was calculated by MRI. NBTXR3 was injected percutaneously into tumors at 53.3 g/L. Dose escalation was based on four levels equivalent to 2.5%, 5%, 10%, and 20% of baseline TV. NBTXR3 was visualized in the tumor 24 hours postinjection, and EBRT was initiated (50 Gy over 5 weeks). Surgery was performed 6 to 8 weeks after EBRT completion.

Results: Twenty-two patients completed NBTXR3 injection, EBRT, and surgery and were followed for a median 22 months (range, 6–40). At NBTXR3 20% of TV, two dose-limiting toxicities occurred: injection-site pain and postoperative scar necrosis. The RD was defined as 10%. No leakage of NBTXR3 into surrounding tissues occurred; intratumor NBTXR3 levels were maintained during radiotherapy. At the RD, median tumor shrinkage was 40% (range 71% shrinkage, 22%increase);median percentage of residual viable tumor cells was 26% (range, 10%–90%). Patients receiving 20% of TV demonstrated pathologic complete responses. Seven grade 3 adverse events occurred, which were reversible.

Conclusion: A single intratumoral injection of NBTXR3 at 10% of TV with preoperative EBRT was technically feasible with manageable toxicity; clinical activity was observed. Clin Cancer Res; 1–10. 2016 AACR.

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