scholarly journals Apatinib with doxorubicin and ifosfamide as neoadjuvant therapy for high-risk soft tissue sarcomas: a retrospective cohort study

Author(s):  
Zhichao Tian ◽  
Jiaqiang Wang ◽  
Jinpo Yang ◽  
Peng Zhang ◽  
Xin Wang ◽  
...  

Summary Background There is a need to establish an effective neoadjuvant therapy for soft tissue sarcomas (STSs). We previously showed that apatinib, administered in combination with doxorubicin-based chemotherapy, improves the efficacy of treatment. This study aimed to clarify the effectiveness and safety of apatinib combined with doxorubicin and ifosfamide (AI) neoadjuvant chemotherapy for STSs. Methods This retrospective study included patients with STS who received neoadjuvant therapy and surgery between January 2016 and January 2019. The patients were divided into two treatment groups: AI + apatinib group and AI group (doxorubicin + ifosfamide). Results The study included 74 patients (AI + apatinib: 26, AI: 48) with STS. There were significant between-group differences in objective response rates (53.85% vs. 29.17%, p = 0.047) and the average change in target lesion size from baseline (-40.46 ± 40.30 vs. -16.31 ± 34.32, p = 0.008). The R0 rate (84.62% vs. 68.75%; p = 0.170) and 2-year disease-free survival (73.08% vs. 62.50%, p = 0.343) were similar across groups. Finally, the rates of neoadjuvant therapy-related adverse effects and postoperative complications were similar in both groups (p > 0.05). Conclusion Apatinib plus doxorubicin and ifosfamide regimen is safe and effective as neoadjuvant therapy for patients with STS. However, the significantly improved preoperative ORR observed after neoadjuvant therapy did not translate into a significantly improved R0 rate and 2-year DFS. Prospective, well-powered studies are warranted to determine the long-term efficacy and optimal application of these protocols.

Cancers ◽  
2021 ◽  
Vol 13 (20) ◽  
pp. 5244
Author(s):  
Miriam Rauch ◽  
Abbas Agaimy ◽  
Sabine Semrau ◽  
Alexander Willner ◽  
Oliver Ott ◽  
...  

Background: Neoadjuvant treatment modalities in soft tissue sarcoma (STS) of the extremities have become more popular in recent years, but because of the rarity and heterogeneity of STS, there are yet few studies on the long-term impact of neoadjuvant treatment modalities, especially in terms of neoadjuvant radiochemotherapy. Methods: The study enrolled 136 patients with primary STS of the extremities who underwent surgery with curative intent or neoadjuvant therapy, followed by surgery in a 15-year period. Neoadjuvant treatment consisted of radiotherapy (RT) with 60 Gy and in most cases simultaneous chemotherapy (CTx) with ifosfamide (1.5 g/m2/d, d1–5, q28) and doxorubicine (50 mg/m2/d, d3, q28). We investigated the clinical, (post)-operative and histopathological data and the oncological follow-up as well. The median follow-up period was 82 months (range 6–202). Results: A total of 136 patients (M:F = 73:63) with a mean age of 62 years (range; 21–93) was observed. Seventy-four patients (54.4%) received neoadjuvant therapy (NT), 62 patients (45.6%) received primary surgery (PS). When receiving NT, patients with high-risk STS had a lower risk to develop distant metastasis (p = 0.025). Age, histological type, tumor size and surgical margins (R0 vs. R1) had no influence on any survival rates. There was an association between NT and the occurrence of postoperative complications (p = 0.001). The 5-year local recurrence free survival (LRFS), metastasis free survival (MFS), disease free survival (DFS) and overall survival (OS) rate of the whole cohort was 89.9%, 77.0%, 70.6% and 72.6%; whereas the 5-year LRFS, MFS, DFS and OS rate was 90.5%, 67.2%, 64.1% and 62.8% for the NT group and 89.5%, 88.3%. 78.4% and 83.8% for the PS group. Conclusion: Multimodal treatment strategies in patients with STS of extremities lead to excellent oncological outcomes. Patients with high-risk STS had a significantly better MFS when receiving NT than patients with low-risk STS. NT was associated with a higher probability of postoperative but well-manageable complications.


2020 ◽  
Author(s):  
Zhichao Tian ◽  
Fan Zhang ◽  
Po Li ◽  
Jiaqiang Wang ◽  
Jinpo Yang ◽  
...  

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.


2013 ◽  
Vol 31 (13) ◽  
pp. 1649-1655 ◽  
Author(s):  
Alessandro Gronchi ◽  
Rosalba Miceli ◽  
Elizabeth Shurell ◽  
Fritz C. Eilber ◽  
Frederick R. Eilber ◽  
...  

Purpose Integration of numerous prognostic variables not included in the conventional staging of retroperitoneal soft tissue sarcomas (RPS) is essential in providing effective treatment. The purpose of this study was to build a specific nomogram for predicting postoperative overall survival (OS) and disease-free survival (DFS) in patients with primary RPS. Patients and Methods Data registered in three institutional prospective sarcoma databases were used. We included patients with primary localized RPS resected between 1999 and 2009. Univariate (Kaplan and Meier plots) and multivariate (Cox model) analyses were carried out. The a priori chosen prognostic covariates were age, tumor size, grade, histologic subtype, multifocality, quality of surgery, and radiation therapy. External validation was performed by applying the nomograms to the patients of an external cohort. The model's discriminative ability was estimated by means of the bootstrap-corrected Harrell C statistic. Results In all, 523 patients were identified at the three institutions (developing set). At a median follow-up of 45 months (interquartile range, 22 to 72 months), 171 deaths were recorded. Five- and 7-year OS rates were 56.8% (95% CI, 51.4% to 62.6%) and 46.7% (95% CI, 39.9% to 54.6%. Two hundred twenty-one patients had disease recurrence. Five- and 7-year DFS rates were 39.4% (95% CI, 34.5% to 45.0%) and 35.7% (95% CI, 30.3% to 42.1%). The validation set consisted of 135 patients who were identified at the fourth institution for external validation. The bootstrap-corrected Harrell C statistics for OS and DFS were 0.74 and 0.71 in the developing set and 0.68 and 0.69 in the validating set. Conclusion These nomograms accurately predict OS and DFS. They should be used for patient counseling in clinical practice and stratification in clinical trials.


2013 ◽  
Vol 137 (12) ◽  
pp. 1774-1779 ◽  
Author(s):  
Hatim Khoja ◽  
Anthony Griffin ◽  
Brendan Dickson ◽  
Jay Wunder ◽  
Peter Ferguson ◽  
...  

Context.—Histologic grade is one of the best predictors of outcome in adult soft tissue sarcomas. Current grading systems were validated on resection specimens; however, there has been a trend toward the use of biopsies to diagnosis these tumors. Objectives.—To determine whether the grade of an extremity soft tissue sarcoma determined on tissue obtained by either core needle biopsy or incisional biopsy is predictive of metastasis- or disease-free survival, and whether either sampling modality is superior. Design.—One hundred three core needle biopsies and 107 incisional biopsies of nonmetastatic spindle cell sarcomas of the extremities were retrieved from the archives. All cases had a minimum 2-year follow-up. Patient data and outcome and tumor characteristics were recorded. Tumors were reviewed and evaluated using the French Federation of Cancer Centers Sarcoma Group grading system. Kaplan-Meier survival curves were generated to correlate tumor grade with metastasis- and disease-free survival for both groups. Results.—Patient and tumor characteristics were similar between groups except that more tumors were grade 3 and superficial in the incisional biopsy group. Grade determined on core needle biopsy was not predictive of either metastasis-free survival (P = .59) or disease-free survival (P = .50). In contrast, grade determined on incisional biopsy was predictive of both metastasis-free survival (P < .001) and disease-free survival (P = .001). Conclusions.—Biopsy, particularly core needle biopsy, represents a convenient diagnostic tool, particularly in the context of neoadjuvant therapy. However, based on these results incisional biopsy is recommended if grading is to be used to predict prognosis in spindle cell soft tissue sarcomas of the extremities.


Sarcoma ◽  
2006 ◽  
Vol 2006 ◽  
pp. 1-6 ◽  
Author(s):  
Quy N. H. Tran ◽  
Anne C. Kim ◽  
Alexander R. Gottschalk ◽  
William M. Wara ◽  
Theodore L. Phillips ◽  
...  

Purpose.Radiation of extremity lesions, a key component of limb-sparing therapy, presents particular challenges, with significant risks of toxicities. We sought to explore the efficacy of intraoperative radiation therapy (IORT) in the treatment of soft tissue sarcomas of the extremities.Patients.Between 1995 and 2001, 17 patients received IORT for soft tissue sarcomas of the extremities. Indications for IORT included recurrent tumors in a previously radiated field or tumors adjacent to critical structures.Results. Gross total resections were achieved in all 17 patients. Two patients experienced locoregional relapses, six patients recurred at metastatic sites, and one patient died without recurrence. Thirty-six month estimates for locoregional control, disease free survival, and overall survival were 86%, 50%, and 78%, respectively. IORT was extremely well tolerated, with no toxicities referable to IORT.Conclusions. For patients with soft tissue sarcomas of the extremities, IORT used as a boost to EBRT provides excellent local control, with limited acute toxicities.


2020 ◽  
Author(s):  
Zhichao Tian ◽  
Fan Zhang ◽  
Po Li ◽  
Jiaqiang Wang ◽  
Jinpo Yang ◽  
...  

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.


2020 ◽  
Author(s):  
Zhichao Tian ◽  
Fan Zhang ◽  
Po Li ◽  
Jiaqiang Wang ◽  
Jinpo Yang ◽  
...  

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.


2006 ◽  
Vol 92 (2) ◽  
pp. 92-97 ◽  
Author(s):  
Sergio Frustaci ◽  
Massimiliano Berretta ◽  
Alessandro Comandone ◽  
Ettore Bidoli ◽  
Antonino De Paoli ◽  
...  

Aims and Background After the first adjuvant study on adult soft tissue sarcomas was concluded, the participating institutions continued to select and treat patients according to that protocol. The aim of this study was to test the protocol reproducibility when applied as a standard practice. Methods A call for retrospective data was launched in June 1999 (self-referral of consecutive unregistered patients); thereafter, a prospective follow-up was performed. The treatment regimen consisted of epirubicin (60 mg/m2 days 1 and 2), ifosfamide (3 g/m2/die for 3 days) and equimolar doses of 6-mercapto-ethansulfonate (MESNA), with 300 μg G-CSF administered subcutaneously from day +8 until recovery, every 3 weeks for a total of 5 cycles. Results From November 1996 to June 1999, 55 high-risk, adult patients were treated. The average median dose intensity was 89% of the planned program. Grade 3-4 toxicities were leukopenia (49%), thrombocytopenia (14%), transfusion requiring anemia in 7 patients (16%), and alopecia in all patients (100%). After a median follow-up of 70 months, 23 patients (41.8%) relapsed and 19 died. Median disease-free, local disease-free and overall survival rates have not yet been reached. The disease-free survival rates at 2 and 4 years were 73% and 57%, respectively; the corresponding overall survival rates were 91% and 70%, respectively. Conclusions The feasibility and reproducibility of the original protocol were confirmed, since disease-specific overall survival and disease-free survival rates at the same period of observation and with the same prolonged follow-up did not differ.


2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 517-517 ◽  
Author(s):  
Frede Donskov ◽  
Robert J. Motzer ◽  
Eric Voog ◽  
Elizabeth J. Hovey ◽  
Carsten Grüllich ◽  
...  

517 Background: In the METEOR study (NCT01865747), cabo demonstrated improved progression-free survival (median 7.4 vs. 3.8 mo; HR 0.58, 95% CI 0.45–0.74; p<0.0001), OS (median 21.4 vs. 16.5 mo; HR 0.66, 95% CI 0.53-0.83, p=0.0003), and objective response rate (17% vs. 3%; p<0.0001) compared with eve in patients (pts) with advanced RCC who had received prior VEGFR TKI therapy (Choueiri NEJM 2015, Lancet Oncol 2016). Here we evaluate the impact of changes in target lesion size from baseline on OS. Methods: 658 pts were randomized 1:1 to receive cabo (60 mg qd) or eve (10 mg qd). Stratification factors were MSKCC risk group and number of prior VEGFR TKIs. Target lesion size was assessed per independent radiology review by CT/MRI scans at baseline, every 8 weeks for the first 12 months, and every 12 weeks thereafter. Three subgroups were defined by best change in target lesion size from baseline: decrease ≥30%, decrease <30%, and any increase. Results: The rate of target lesion regression was higher in the cabo arm (75%) compared with the eve arm (48%). A higher fraction of pts had a decrease ≥30% in target lesion size in the cabo arm, while a higher fraction of pts had an increase in target lesion size in the eve arm (Table). Medians for OS with cabo were not estimable (NE) (95% CI, NE‒NE), 20.8 mo (95% CI, 18.1‒NE), and 11.1 mo (95% CI, 7.6‒15.2) for the ≥30% decrease, <30% decrease, and any increase subgroups, respectively. Medians for OS with eve were NE (95% CI, 19.3‒NE), 18.0 mo (95% CI, 15.9‒20.4), and 14.0 mo (95% CI, 10.5‒16.3) for the ≥30% decrease, <30% decrease, and any increase subgroups, respectively. Median duration of follow-up for OS was 18.7 mo (IQR 16.1–21.1) for cabo and 18.8 mo (16.0–21.2) for eve. A higher proportion of pts received subsequent anticancer therapy in the any increase subgroup compared with the other subgroups. Conclusions: Cabo demonstrated a higher rate of tumor target lesion regression than eve, and greater target lesion regression was associated with improved OS in pts with advanced RCC. Clinical trial information: NCT01865747.


2019 ◽  
Vol 27 (4) ◽  
pp. 207-211
Author(s):  
Özlem Yetmen Dogan ◽  
Didem Çolpan Oksuz ◽  
Banu Atalar ◽  
Fazilet Oner Dincbas

ABSTRACT Objective: To assess the prognostic factors and results of limb sparing surgery and postoperative radiotherapy (PORT) in patients with non-metastatic soft tissue sarcomas (STS) of the extremities. Methods: Between 1980-2007, 114 extremity-located STS treated with PORT were analyzed retrospectively. Tumors were mostly localized in the lower extremities (71,9%). The median radiotherapy (RT) dose was 60.9 Gy. Chemotherapy was administered to 37.7% of the patients. Tumor sizes were between 3-26 cm (median 7 cm). The three most frequent histological types included undifferentiated pleomorphic sarcoma (26.3%), liposarcoma (25.4%), and synovial sarcoma (13.2%). The median follow-up for all patients was 60 months, and 81 months for survivors. Results: The 5- and 10-year local control (LC) rates were 77% and 70.4%, respectively; actuarial survival rates for 5 and 10 years were 71.8% and 69.1%, respectively. Increasing the dose above 60 Gy for all patients and the patients with positive margins demonstrated a clear benefit on 5-year LC (p=0.03 and p=0.04, respectively). Based on multivariate analysis, the addition of chemotherapy and RT dose were independent prognostic factors for LC. A recurrent presentation significantly affects the disease-free survival. Conclusions: PORT for STS of the extremities provides good long-term disease control with acceptable toxicity in a multidisciplinary approach. Level of evidence III, Retrospective study.


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