PET Response Criteria in Solid Tumors Predicts Progression-Free Survival and Time to Local or Distant Progression After Chemotherapy with Regional Hyperthermia for Soft-Tissue Sarcoma

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.

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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

Journal of Clinical Oncology ◽

10.1200/jco.2005.01.180 ◽

2005 ◽

Vol 23 (3) ◽

pp. 576-584 ◽

Cited By ~ 301

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.

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

10.21203/rs.3.rs-23150/v1 ◽

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.

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

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.11073 ◽

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.

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

Tumori Journal ◽

10.1177/0300891618792479 ◽

2018 ◽

Vol 105 (2) ◽

pp. 138-143 ◽

Cited By ~ 3

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

Trials ◽

10.1186/s13063-021-05069-z ◽

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

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Ifosfamide, Carboplatin, and Etoposide (ICE) in Combination with Regional Hyperthermia as Salvage Therapy in Patients with Locally Advanced Nonmetastatic and Metastatic Soft-Tissue Sarcoma

Sarcoma ◽

10.1155/2020/6901678 ◽

2020 ◽

Vol 2020 ◽

pp. 1-10 ◽

Cited By ~ 2

Author(s):

Veit Bücklein ◽

Christina Limmroth ◽

Eric Kampmann ◽

Gesa Schuebbe ◽

Rolf Issels ◽

...

Keyword(s):

High Risk ◽

Soft Tissue ◽

Soft Tissue Sarcoma ◽

Disease Control ◽

Locally Advanced ◽

Progression Free Survival ◽

Tumor Control ◽

Regional Hyperthermia ◽

Radiographic Response ◽

Dismal Prognosis

Patients with localized relapse of soft-tissue sarcoma (STS) after anthracycline-based chemotherapy have a dismal prognosis, particularly when surgery is not possible. To facilitate resection and improve long-term tumor control, we applied an intensified perioperative treatment consisting of ICE (ifosfamide 6 g/m2, carboplatin 400 mg/m2, and etoposide 600 mg/m2) in combination with regional hyperthermia (RHT) to maximize local control. Here, we retrospectively evaluate the safety and efficacy of this strategy. Patients aged ≥18 years with locally advanced high-risk STS, either with or without metastasis, treated with ICE + RHT after the failure of first-line anthracycline-based chemotherapy were included in this analysis. Radiographic response, toxicity, progression-free survival (PFS), and overall survival (OS) were assessed. Between 1996 and 2018, 213 sarcoma patients received ICE at our centre. Of these, 110 patients met the selection criteria (progressive disease, suitable high-grade STS histology, anthracycline pretreatment, RHT treatment) for this analysis. Fifty-four patients had locally advanced disease without metastases (LA-STS), and 56 patients had additional metastatic disease (M-STS). Disease control was achieved in 59% of LA-STS patients and in 47% of M-STS patients. For LA-STS, 21% of the patients achieved radiographic response, facilitating resection in 4 patients (7%), compared with 11% of the M-STS patients, facilitating resection in 5 patients (9%). PFS was significantly longer in LA-STS than in M-STS (10 vs. 4 months, p<0.0001). Median OS was 26 months in LA-STS and 12 months in M-STS. Disease control was the only independent prognostic factor for improved OS in multivariate analysis. Toxicity was high with neutropenic fever occurring in 25% of the patients and three therapy-related deaths (3%). ICE + RHT demonstrated activity in high-risk STS and facilitated resection in selected patients after anthracycline failure. Disease control was associated with improved OS. Based on the observed toxicities, the dose should be reduced to 75%.

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Phase III Trial of Two Investigational Schedules of Ifosfamide Compared With Standard-Dose Doxorubicin in Advanced or Metastatic Soft Tissue Sarcoma: A European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group Study

Journal of Clinical Oncology ◽

10.1200/jco.2006.09.7717 ◽

2007 ◽

Vol 25 (21) ◽

pp. 3144-3150 ◽

Cited By ~ 178

Author(s):

Paul Lorigan ◽

Jaap Verweij ◽

Zsuzsa Papai ◽

Sjoerd Rodenhuis ◽

Axel Le Cesne ◽

...

Keyword(s):

Overall Survival ◽

Soft Tissue ◽

Soft Tissue Sarcoma ◽

Standard Dose ◽

Single Agent ◽

Progression Free Survival ◽

Phase Iii ◽

Advanced Soft Tissue Sarcoma ◽

Phase Iii Trial ◽

Free Survival

Purpose Single-agent doxorubicin remains the standard treatment for advanced soft tissue sarcomas. Combining doxorubicin with standard-dose ifosfamide has not been shown to improve survival and is associated with a significantly increased toxicity; it is not known whether higher dose single-agent ifosfamide is superior to doxorubicin. Patients and Methods This randomized prospective multicenter phase III trial was designed to compare progression-free survival of patients with advanced soft tissue sarcoma receiving either regimen of standard doxorubicin 75 mg/m2 every 21 days, ifosfamide 9 g/m2 over 3 days continuous infusion, or ifosfamide 3 g/m2 per day in 3 hours over 3 days. The primary end point was progression-free survival. Secondary end points included overall survival, response rate, and toxicity. Results The study included 326 patients. Grade 4 leukopenia, neutropenia, febrile neutropenia, and encephalopathy were more frequent in the ifosfamide arms. Progression-free survival, overall survival, and response rates were not significantly different between the three arms. An independent data monitoring committee reviewed the interim data and recommended early closure of the trial for futility (ie, no significant difference would be shown). Conclusion Single-agent doxorubicin remains the treatment of choice for patients with advanced soft tissue sarcoma.

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PD-L1 Tumour Expression is Predictive of Pazopanib Response in Soft Tissue Sarcoma

10.21203/rs.3.rs-76201/v1 ◽

2020 ◽

Author(s):

Sang Kyun Kim ◽

Jee Hung Kim ◽

Seung Hyun Kim ◽

Young Han Lee ◽

Jung Woo Han ◽

...

Keyword(s):

Soft Tissue ◽

Soft Tissue Sarcoma ◽

Kinase Inhibitor ◽

Progression Free Survival ◽

Poor Response ◽

Free Survival ◽

Viable Cells ◽

Molecular Determinants ◽

Multitargeted Tyrosine Kinase Inhibitor ◽

To Receive

Abstract Background Pazopanib, a multitargeted tyrosine kinase inhibitor, is recommended as the standard treatment for refractory soft tissue sarcoma (STS). However, there are comparatively few molecular determinants for predicting pazopanib efficacy. Based on correlative studies regarding the predictive impact of PD-L1, we investigated the clinical relevance of PD-L1 expression and evaluated its value for predicting pazopanib efficacy. Methods Tumour tissues from patients with advanced STS who went on to receive pazopanib were assessed for PD-L1 expression. Immunohistochemistry was performed using an anti-PD-L1 antibody, and the PD-L1 tumour proportion score (TPS) was calculated as the percentage of at least 100 viable cells with positive expression, defined as TPS ≥ 1%. ResultsAmong the 67 patients, 8 (11.9%) achieved partial response and a median progression-free survival (PFS) of 4.8 months (95% CI 3.8-5.7). PD-L1 expression in tumour cells was detected in 13 (19.4%) cases and the TPS scores ranged from 1‒100%, as follows: 0 (n=54, 80.6%), 1‒9% (n=3, 4.5%), 10‒49% (n=9, 13.4%), and ≥50% (n=1, 1.5%). PD-L1 positive tumours exhibited a poorer response to pazopanib treatment than the PD-L1 negative tumours (0% vs 14.8%, P=0.07). PD-L1-positive tumours had significantly shorter PFS than the PD-L1-negative tumours (median PFS 2.8 vs 5.1 months, P=0.003), and PD-L1 positivity was an independent predictor of poor response to pazopanib treatment (HR 2.77, 95% CI; 1.45-5.56, P=0.006). ConclusionWe identified that PD-L1 expression can help predict the clinical outcome of patients with advanced STS treated with pazopanib. Based on our study, stratification should be actively considered in order to identify patients who will benefit from pazopanib or further therapeutic strategies for future clinical trials.

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PD-L1 tumour expression is predictive of pazopanib response in soft tissue sarcoma

BMC Cancer ◽

10.1186/s12885-021-08069-z ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Sang Kyum Kim ◽

Jee Hung Kim ◽

Seung Hyun Kim ◽

Young Han Lee ◽

Jung Woo Han ◽

...

Keyword(s):

Soft Tissue ◽

Soft Tissue Sarcoma ◽

Kinase Inhibitor ◽

Progression Free Survival ◽

Poor Response ◽

Free Survival ◽

Viable Cells ◽

Molecular Determinants ◽

Multitargeted Tyrosine Kinase Inhibitor ◽

To Receive

Abstract Background Pazopanib, a multitargeted tyrosine kinase inhibitor, is recommended as the standard treatment for refractory soft tissue sarcoma (STS). However, there are comparatively few molecular determinants for predicting pazopanib efficacy. Based on correlative studies regarding the predictive impact of PD-L1, we investigated the clinical relevance of PD-L1 expression and evaluated its value for predicting pazopanib efficacy. Methods Tumour tissues from patients with advanced STS who went on to receive pazopanib were assessed for PD-L1 expression. Immunohistochemistry was performed using an anti-PD-L1 antibody, and the PD-L1 tumour proportion score (TPS) was calculated as the percentage of at least 100 viable cells with positive expression, defined as TPS ≥ 1%. Results Among the 67 patients, 8 (11.9%) achieved partial response and a median progression-free survival (PFS) of 4.8 months (95% CI 3.8–5.7). PD-L1 expression in tumour cells was detected in 13 (19.4%) cases and the TPS scores ranged from 1 to 100%, as follows: 0 (n = 54, 80.6%), 1–9% (n = 3, 4.5%), 10–49% (n = 9, 13.4%), and ≥ 50% (n = 1, 1.5%). PD-L1 positive tumours exhibited a poorer response to pazopanib treatment than the PD-L1 negative tumours (0% vs 14.8%, P = 0.07). PD-L1-positive tumours had significantly shorter PFS than the PD-L1-negative tumours (median PFS 2.8 vs 5.1 months, P = 0.003), and PD-L1 positivity was an independent predictor of poor response to pazopanib treatment (HR 2.77, 95% CI; 1.45–5.56, P = 0.006). Conclusion We identified that PD-L1 expression can help predict the clinical outcome of patients with advanced STS treated with pazopanib. Based on our study, stratification should be actively considered in order to identify patients who will benefit from pazopanib or further therapeutic strategies for future clinical trials.

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