scholarly journals Neoadjuvant irradiation of retroperitoneal soft tissue sarcoma with ions (Retro-Ion): study protocol for a randomized phase II pilot trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
K. Seidensaal ◽  
M. Kieser ◽  
A. Hommertgen ◽  
C. Jaekel ◽  
S. B. Harrabi ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Phase Ii ◽  
Local Control ◽  
Preoperative Radiotherapy ◽  
Combined Treatment ◽  
Progression Free Survival ◽  
Particle Therapy ◽  
Free Survival ◽  
Carbon Ion

Abstract Background Following surgery for soft tissue sarcoma of the retroperitoneum, the predominant pattern of failure is local recurrence, which remains the main cause of death. Radiotherapy is utilized to reduce recurrence rates but the efficacy of this strategy has not been definitely established. As treatment tolerability is more favorable with preoperative radiotherapy, normofractionated neoadjuvant treatment is the current approach. The final results of the prospective, randomized STRASS (EORTC 62092) trial, which compared the efficacy of this combined treatment to that of surgery alone, are still awaited; preliminary results presented at the 2019 ASCO Annual Meeting indicated that combined treatment is associated with better local control in patients with liposarcoma (74.5% of the cohort, 11% benefit in abdominal progression free survival after 3 years, p = 0.049). Particles allow better sparing of surrounding tissues at risk, e.g., bowel epithelium, and carbon ions additionally offer biologic advantages and are preferred in slow growing tumors. Furthermore, hypofractionation allows for a significantly shorter treatment interval with a lower risk of progression during radiotherapy. Methods and design We present a prospective, randomized, monocentric phase II trial. Patients with resectable or marginally resectable, histologically confirmed soft tissue sarcoma of the retroperitoneum will be randomized between neoadjuvant proton or neoadjuvant carbon ion radiotherapy in active scanning beam application technique (39 Gy [relative biological effectiveness, RBE] in 13 fractions [5–6 fractions per week] in each arm). The primary objective is the safety and feasibility based on the proportion of grade 3–5 toxicity (CTCAE, version 5.0) in the first 12 months after surgery or discontinuation of treatment for any reason related to the treatment. Local control, local progression-free survival, disease-free survival, overall survival, and quality of life are the secondary endpoints of the study. Discussion The aim of this study is to confirm that hypofractionated, accelerated preoperative radiotherapy is safe and feasible. The rationale for the use of particle therapy is the potential for reduced toxicity. The data will lay the groundwork for a randomized phase III trial comparing hypofractionated proton and carbon ion irradiation with regard to local control. Trial registration ClinicalTrials.gov NCT04219202. Retrospectively registered on January 6, 2020

Phase II Study of ET-743 in Advanced Soft Tissue Sarcomas: A European Organisation for the Research and Treatment of Cancer (EORTC) Soft Tissue and Bone Sarcoma Group Trial

2005 ◽  
Vol 23 (3) ◽  
pp. 576-584 ◽  
Author(s):  
A. Le Cesne ◽  
J.Y. Blay ◽  
I. Judson ◽  
A. Van Oosterom ◽  
J. Verweij ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Phase Ii ◽  
Median Duration ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Advanced Soft Tissue Sarcoma ◽  
Free Survival ◽  
Grade 3 ◽  
Line Chemotherapy

Purpose This nonrandomized multicenter phase II study was performed to evaluate the activity and safety of Ecteinascidin (ET-743) administered at a dose of 1.5 mg/m2 as a 24-hour continuous infusion every 3 weeks in patients with pretreated advanced soft tissue sarcoma. Patients and Methods Patients with documented progressive advanced soft tissue sarcoma received ET-743 as second- or third-line chemotherapy. Antitumor activity was evaluated every 6 weeks until progression, excessive toxicity, or patient refusal. Results One hundred four patients from eight European institutions were included in the study (March 1999 to November 2000). A total of 410 cycles were administered in 99 assessable patients. Toxicity mainly involved reversible grade 3 to 4 asymptomatic elevation of transaminases in 40% of patients, and grade 3 to 4 neutropenia was observed in 52% of patients. There were eight partial responses (PR; objective regression rate, 8%), 45 no change (NC; > 6 months in 26% of patients), and 39 progressive disease. A progression arrest rate (PR + NC) of 56% was observed in leiomyosarcoma and 61% in synovialosarcoma. The median duration of the time to progression was 105 days, and the 6-month progression-free survival was 29%. The median duration of survival was 9.2 months. Conclusion ET-743 seems to be a promising active agent in advanced soft tissue sarcoma, with no cumulative toxicities. The 6-months progression-free survival observed in advanced soft tissue sarcoma compares favorably with those obtained with other active drugs tested in second-line chemotherapy in previous European Organisation for the Research and Treatment of Cancer trials. The median overall survival was unusually long in these heavily pretreated patients mainly due to the high number of patients who benefit from the drug in terms of tumor control.

Randomized Phase II Study Comparing Gemcitabine Plus Dacarbazine Versus Dacarbazine Alone in Patients With Previously Treated Soft Tissue Sarcoma: A Spanish Group for Research on Sarcomas Study

2011 ◽  
Vol 29 (18) ◽  
pp. 2528-2533 ◽  
Author(s):  
Xavier García-del-Muro ◽  
Antonio López-Pousa ◽  
Joan Maurel ◽  
Javier Martín ◽  
Javier Martínez-Trufero ◽  
...  
Keyword(s):  
Overall Survival ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Fixed Dose ◽  
Disease Rate ◽  
Free Survival ◽  
Previously Treated

Purpose To assess the activity and toxicity of the combination of gemcitabine plus dacarbazine (DTIC) in patients with advanced soft tissue sarcoma (STS) in a randomized, multicenter, phase II study using DTIC alone as a control arm. Patients and Methods Patients with previously treated advanced STS were randomly assigned to receive either fixed-dose rate gemcitabine (10 mg/m2/min) at 1,800 mg/m2 followed by DTIC at 500 mg/m2 every 2 weeks, or DTIC alone at 1,200 mg/m2 every 3 weeks. The primary end point of the study was progression-free rate (PFR) at 3 months. Results From November 2005 to September 2008, 113 patients were included. PFR at 3 months was 56% for gemcitabine plus DTIC versus 37% for DTIC alone (P = .001). Median progression-free survival was 4.2 months versus 2 months (hazard ratio [HR], 0.58; 95% CI, 0.39 to 0.86; P = .005), and median overall survival was 16.8 months versus 8.2 months (HR, 0.56; 95% CI, 0.36 to 0.90; P = .014); both favored the arm of gemcitabine plus DTIC. Gemcitabine plus DTIC was also associated with a higher objective response or higher stable disease rate than was DTIC alone (49% v 25%; P = .009). Severe toxicities were uncommon, and treatment discontinuation for toxicity was rare. Granulocytopenia was the more common serious adverse event, but febrile neutropenia was uncommon. Asthenia, emesis, and stomatitis were the most frequent nonhematologic effects. Conclusion The combination of gemcitabine and DTIC is active and well tolerated in patients with STS, providing in this phase II randomized trial superior progression-free survival and overall survival than DTIC alone. This regimen constitutes a valuable therapeutic alternative for these patients.

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.

scholarly journals Anti-Angiogenic Agents in Management of Sarcoma Patients: Overview of Published Trials

2020 ◽  
Vol 10 ◽  
Author(s):  
Pierre-Yves Cren ◽  
Loïc Lebellec ◽  
Thomas Ryckewaert ◽  
Nicolas Penel
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Phase Ii ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Phase Ii Trials ◽  
Double Blind ◽  
Multikinase Inhibitors ◽  
Randomized Phase Ii ◽  
Phase Iii Trials

We reviewed all fully published clinical trials assessing anti-angiogenic agents in sarcoma patients (last issue, January 13, 2020). Anti-angiogenic macromolecules (e.g., bevacizumab or ombrabulin) provide disappointing results. Many multikinase inhibitors have been assessed with non-randomized phase II trials with limited samples and without stratification according to histological subtypes, therefore interpretation of such trials is very challenging. On the contrary, pazopanib, regorafenib, and sorafenib have been assessed using double-blind placebo-controlled randomized phase II or phase III trials. Compared to placebo, sorafenib demonstrates activity in desmoid-type fibromatosis patients. Based on results of phase 3 trial, pazopanib had obtained approval for treatment of pretreated non-adipocytic soft tissue sarcoma. Regorafenib is currently assessed in several clinical settings and provides significant improvement of progression-free survival in pre-treated non-adipocytic soft tissue sarcoma and in advanced pretreated osteosarcoma. Multikinase inhibitors are a breakthrough in sarcoma management. Many trials are ongoing. Nevertheless, predictive factors are still missing.

scholarly journals Effectiveness of Carbon Ion Radiation in Locally Advanced Pancreatic Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Jakob Liermann ◽  
Patrick Naumann ◽  
Fabian Weykamp ◽  
Philipp Hoegen ◽  
Juergen Debus ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Local Control ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Locally Advanced Pancreatic Cancer ◽  
Carbon Ion Radiotherapy ◽  
Free Survival ◽  
Carbon Ion

PurposeEffective treatment strategies for unresectable locally advanced pancreatic cancer (LAPC) patients are eagerly warranted. Recently, convincing oncological outcomes were demonstrated by carbon ion radiotherapy. Nevertheless, there is a lack of evidence for this modern radiation technique due to the limited number of carbon ion facilities worldwide. Here, we analyze feasibility and efficacy of carbon ion radiotherapy in the management of LAPC at Heidelberg Ion Beam Therapy Center (HIT).MethodsBetween 2015 and 2020, 21 LAPC patients were irradiated with carbon ions with a total dose of 48 Gy (RBE) in single doses of 4 Gy (RBE). Three patients (14%) were treated with concomitant chemotherapy with gemcitabine 300 mg/m2 body surface weekly. Toxicity rates were extracted from the charts. Overall survival, progression free survival, local control, and locoregional control were evaluated using Kaplan–Meier estimates.ResultsOne patient developed ascites CTCAE grade III during radiotherapy, which was related to a later histologically confirmed metachronous peritoneal carcinomatosis. No further higher-graded toxicity could be observed. The most common symptoms were nausea and abdominal pain. After a median estimated follow-up time of 19.1 months, the median progression free survival was 3.7 months, and the median overall survival was 11.9 months. The estimated 1-year local control and locoregional control rates were 89 and 84%, respectively.ConclusionCarbon ion radiotherapy of LAPC patients is safely feasible. Local tumor control rates were high. Nevertheless, compared to historical data, an overall survival improvement could not be observed. This could be explained by the poor prognosis of the selected underlying patients that mostly did not respond to prior chemotherapy as well as the early and frequent emergence of distant metastases that demonstrate the necessity of additional chemotherapy in further studies.

scholarly journals Albumin-bound paclitaxel and gemcitabine combination therapy in soft tissue sarcoma

2020 ◽  
Author(s):  
Zhichao Tian ◽  
Fan Zhang ◽  
Po Li ◽  
Jiaqiang Wang ◽  
Jinpo Yang ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Malignant Tumors ◽  
Objective Response ◽  
Progression Free Survival ◽  
Target Lesion ◽  
Free Survival ◽  
Metastatic Soft Tissue Sarcoma ◽  
Low Toxicity ◽  
Grade 3

Abstract Background: The evidence that albumin-bound paclitaxel (nab-paclitaxel) is safe and efficacious for the treatment of many types of malignant tumors is continuously increasing. However, the clinical data and evidence of nab-paclitaxel and gemcitabine in metastatic soft tissue sarcoma (STS) treatment are rare.Methods: The data of 17 patients with metastatic STS who received nab-paclitaxel/ gemcitabine chemotherapy between January 2019 and February 2020 were retrospectively reviewed. All patients were treated with nab-paclitaxel/ gemcitabine only after doxorubicin-based chemotherapy had failed. We evaluated the median progression-free survival (m-PFS), disease control rate (DCR), objective response rate (ORR) and adverse events (AEs) in these patients.Results: The m-PFS was 6 months (95% CI, 2–9 months), ORR was 41.2% and DCR was 70.6%. The average change in target lesion diameter from baseline was -19.06±45.74%. While the majority of the treatment patients experienced grade 1 or 2 AEs, grade 3 or 4 AEs were not common, but included neutropenia (17.6%), fatigue (11.8%), anemia (11.8%), leukopenia (11.8%), nausea (5.9%), peripheral neuropathy (5.9%), diarrhea (5.9%), and thrombocytopenia (5.9%). No treatment-related deaths occurred. Conclusion: Nab-paclitaxel/ gemcitabine combination chemotherapy is comparatively effective in the treatment of STS, demonstrates low toxicity, and is worthy of further study.

Efficacy and dosimetry prognostic factors of image guided 125I seed implantation for locally recurrent soft tissue sarcoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 11073-11073
Author(s):  
Weijuan Jiang ◽  
Ping Jiang ◽  
Ang Qu ◽  
Junjie Wang ◽  
Haitao Sun
Keyword(s):  
Overall Survival ◽  
Survival Rate ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Survival Rates ◽  
Progression Free Survival ◽  
Ct Guided ◽  
Free Survival ◽  
Seed Implantation ◽  
Local Progression

11073 Background: To observe the effect of ultrasound / CT guided radioactive 125I seed implantation in the treatment of recurrent soft tissue sarcoma and its relationship with physical dosimetry prognostic factors. Methods: The data of 37 patients with recurrent soft tissue sarcoma who received ultrasound/CT-guided 125I seed implantation from November 2005 to December 2015 were retrospectively analyzed. The local progression-free survival rate and overall survival rate were evaluated. The relationship of local progression-free survival rate and overall survival with physical dosimetric parameters was analyzed. Results: Thirty-seven patients, 20 males and 17 females, with a median age of 53 years (16-79 years), received a median radiation dose of 60 Gy (28 Gy-120 Gy). The median tumor volume was 46.8 cm3 (0.5-252.2 cm3), the median particle activity was 0.67 mCi (0.4-0.84 mCi), and the median implanted particle number was 60 (3-158). The median follow-up time was 20 months (range: 1~144 months). The median overall survival time was 20.0 months (95% CI 16.4-23.6 months). The overall survival rates of 1, 3 and 5 years were 62.2%, 34.3% and 27.7% respectively. The median local progression-free time was 63.0 months. The 1-year, 3-year and 5-year local progression-free survival rates were 68.9%, 55.0% and 47.1%, respectively. Correlation analysis showed that HI was positively correlated with total survival and local progression-free survival (P = 0.001). Multivariate analysis showed that HI ( > 0.25) was an independent prognostic factor for long overall survival (P = 0.048, HR 0.39), and D90 ( > 110 Gy) was an independent prognostic factor for long local progression-free survival (P = 0.024, HR 0.17). Conclusions: Ultrasound/CT guided 125I seed implantation is a safe and effective method for the treatment of recurrent soft tissue sarcoma with high local control rate. The HI and D90 of the postoperative plan maybe affect the therapeutic efficacy.

Topotecan/carboplatin regimen for refractory/recurrent rhabdomyosarcoma in children: Report from the AIEOP Soft Tissue Sarcoma Committee

2018 ◽  
Vol 105 (2) ◽  
pp. 138-143 ◽  
Author(s):  
Alessia Compostella ◽  
Maria Carmen Affinita ◽  
Michela Casanova ◽  
Giuseppe Maria Milano ◽  
Angela Scagnellato ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Tumor Response ◽  
Survival Rates ◽  
Progression Free Survival ◽  
Late Relapse ◽  
Hematologic Toxicity ◽  
Free Survival ◽  
Grade 3 ◽  
Experienced Grade

Introduction: From 2002 to 2011, the Italian Soft Tissue Sarcoma Committee explored a combination of topotecan and carboplatin as a second-line strategy for children with resistant or relapsing rhabdomyosarcoma. Methods: Patients received two blocks of topotecan 2 mg/m2 on days 1, 2, and 3, and carboplatin 250 mg/m2 on days 4 and 5, followed by alternating blocks of topotecan–cyclophosphamide and carboplatin–etoposide for a total of six courses with 3-week intervals. Tumor response was assessed after two cycles, and local control was implemented when feasible. Results: A total of 38 patients were included in this study: 18/38 had alveolar rhabdomyosarcoma (RMS), 10/38 had metastatic disease at diagnosis, 8/38 had tumor progression during first-line chemotherapy, 21/38 had locoregional relapses, and 9/38 had distant relapses. Thirty-two patients could be assessed for tumor response to topotecan–carboplatin, and 9 (28%) showed a complete or partial response. Twenty-four patients experienced grade IV hematologic toxicity, while transient grade 1 tubulopathy, grade 3 mucositis, transient grade 2 nephrotoxicity, and a grade 2 decline in cardiac function occurred in one patient each. The 5-year overall and progression-free survival rates were 17% and 14%, respectively. Conclusion: the prognosis for children with resistant or relapsing RMS remains unsatisfactory. The topotecan–carboplatin regimen was well-tolerated. Though in case of late relapse the response rate was similar to those reported for other regimes, the result achieved remains unsatisfactory. New approaches, possibly including target agents, seem more attractive for future studies.

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