Cohort Analysis of Patients With Localized, High-Risk, Extremity Soft Tissue Sarcoma Treated at Two Cancer Centers: Chemotherapy-Associated Outcomes

2004 ◽  
Vol 22 (22) ◽  
pp. 4567-4574 ◽  
Author(s):  
Janice N. Cormier ◽  
Xuelin Huang ◽  
Yan Xing ◽  
Peter F. Thall ◽  
Xuemei Wang ◽  
...  
Keyword(s):  
High Risk ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Local Therapy ◽  
Distant Recurrence ◽  
Hazard Ratio ◽  
Stage Iii ◽  
Clinical Benefits ◽  
The Impact

Purpose Patients with American Joint Committee on Cancer stage III soft tissue sarcoma (STS) have high risks of distant recurrence and death. The role of chemotherapy for these patients remains controversial despite several randomized trials and a meta-analysis. Methods We reviewed the treatments and outcomes of 674 consecutive adult patients presenting with primary stage III extremity STS between 1984 and 1999. Pre- or postoperative doxorubicin-based chemotherapy was used in a nonrandomized fashion in approximately half of this high-risk population. The objective of this review was to evaluate the impact of chemotherapy while accounting for known prognostic variables. Results Among 674 patients, 338 (50%) were treated with local therapy only, and 336 (50%) were treated with local therapy plus chemotherapy. The median follow-up for survivors was 6.1 years. Five-year local and distant recurrence-free interval probabilities were 83% and 56%, respectively, for the two groups combined. The 5-year disease-specific survival (DSS) rate was 61%. Cox regression analyses showed a time-varying effect associated with chemotherapy. During the first year, the hazard ratio associated with DSS for patients treated with chemotherapy versus no chemotherapy was 0.37 (95% CI, 0.20 to 0.69; P = .002). Thereafter, this hazard ratio was 1.36 (95% CI, 1.02 to 1.81; P = .04). Conclusion It seems that the clinical benefits associated with doxorubicin-based chemotherapy in patients with high-risk extremity STS are not sustained beyond 1 year. These results suggest that caution should be used in the interpretation of randomized clinical trials of adjuvant chemotherapy that seem to demonstrate clinical benefits with relatively short-term follow-up.

scholarly journals Outcome and Toxicity of an Ifosfamide-Based Soft Tissue Sarcoma Treatment Protocol in Children. The Importance of Local Therapy

Sarcoma ◽  
1998 ◽  
Vol 2 (3-4) ◽  
pp. 171-177
Author(s):  
S. Murray Yule ◽  
Roderick Skinner ◽  
Martin W. English ◽  
Mike Cole ◽  
Andrew D. J. Pearson ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Primary Tumour ◽  
Treatment Protocol ◽  
Disease Free Survival ◽  
Local Therapy ◽  
Complete Response ◽  
One Year ◽  
Sarcoma Treatment

Background.Although the survival of children with soft tissue sarcoma (STS) has improved considerably, the outcome of patients with metastatic disease, and those with primary tumours of the extremities or parameningeal sites remains disappointing. We describe the clinical outcome of an ifosfamide-based regimen with local therapy directed only to children who failed to achieve a complete response to initial chemotherapy.Patients and Methods.Twenty-one children with STS (16 rhabdomyosarcoma) who presented with unresectable tumours were treated with five courses of ifosfamide (9 g/m2) and etoposide (600 mg/m2). Patients who did not achieve a complete response then received local therapy. Chemotherapy with ifosfamide combined with etoposide, vincristine (1.5 mg/m2and doxorubicin (60 mg/m2) or vincristine and actinomycin D (1.5 mg/m2) was continued for one year.Results and Discussion.Objective responses to five courses of ifosfamide and etoposide were seen in all patients. Disease free survival (DFS) at a median follow up of 59 months was 57% (95% CI 29–75%). The DFS of children who received local therapy was 89% compared with 33% in those who received chemotherapy alone (p=0.027). Locoregional recurrences did not occur in children who received radiotherapy to the site of the primary tumour. Ifosfamide-based chemotherapy does not reduce the incidence of loco-regional recurrence in children who do not receive local therapy.

The Use of Adjuvant or Neoadjuvant Chemotherapy in Extremity and Truncal Sarcoma

2018 ◽  
Author(s):  
Robert J Canter
Keyword(s):  
Soft Tissue ◽  
Neoadjuvant Chemotherapy ◽  
Soft Tissue Sarcoma ◽  
Synovial Sarcoma ◽  
Distant Recurrence ◽  
Curative Intent ◽  
Pleomorphic Sarcoma ◽  
Level I ◽  
Meta Analyses ◽  
The Impact

Although neoadjuvant chemotherapy has been an established component of multimodality cancer care for patients with pediatric sarcomas for the past 25 years, the role of adjuvant or neoadjuvant chemotherapy in the management of adult patients with soft tissue sarcoma (STS) amenable to treatment with curative intent remains controversial. Overall, meta-analyses have revealed modest improvements in survival outcomes with the use of adjuvant or neoadjuvant chemotherapy, but individual trials have demonstrated inconsistent results leading some to question the robustness and external validity of the results. A recent randomized trial using anthracycline- and ifosfamide-based chemotherapy has provided further positive evidence in support of neoadjuvant chemotherapy for adult STS patients, but concerns persist regarding the risks of chemotherapy-related toxicities and the generalizability of the findings. Given the substantial risk of distant recurrence and disease-specific death for adult STS patients with tumors greater than 10 cm, especially those with synovial sarcoma and myxoid or round liposarcoma histologies, these patients should be strongly considered for neoadjuvant chemotherapy as part of a combined modality approach. The impact of recent level I data on the broader implementation of adjuvant or neoadjuvant chemotherapy in adult STS remains to be seen.  This review contains 5 figures and 34 references Key Words: chemotherapy, limb salvage, myxoid/round cell liposarcoma, multimodality therapy, soft tissue sarcoma, surgery, survival, synovial sarcoma, undifferentiated pleomorphic sarcoma  

scholarly journals Longer Follow-Up Confirms Recurrence-Free Survival Benefit of Adjuvant Pembrolizumab in High-Risk Stage III Melanoma: Updated Results From the EORTC 1325-MG/KEYNOTE-054 Trial

2020 ◽  
Vol 38 (33) ◽  
pp. 3925-3936 ◽  
Author(s):  
Alexander M. M. Eggermont ◽  
Christian U. Blank ◽  
Mario Mandala ◽  
Georgina V. Long ◽  
Victoria G. Atkinson ◽  
...  
Keyword(s):  
Lymph Node ◽  
High Risk ◽  
Phase Iii ◽  
Stage Iii ◽  
Recurrence Free Survival ◽  
Meaningful Improvement ◽  
Free Survival ◽  
Stage Iii Melanoma ◽  
The Impact

PURPOSE We conducted the phase III double-blind European Organisation for Research and Treatment of Cancer (EORTC) 1325/KEYNOTE-054 trial to evaluate pembrolizumab versus placebo in patients with resected high-risk stage III melanoma. On the basis of 351 recurrence-free survival (RFS) events at a 1.25-year median follow-up, pembrolizumab prolonged RFS (hazard ratio [HR], 0.57; P < .0001) compared with placebo. This led to the approval of pembrolizumab adjuvant treatment by the European Medicines Agency and US Food and Drug Administration. Here, we report an updated RFS analysis at the 3.05-year median follow-up. PATIENTS AND METHODS A total of 1,019 patients with complete lymph node dissection of American Joint Committee on Cancer Staging Manual (seventh edition; AJCC-7), stage IIIA (at least one lymph node metastasis > 1 mm), IIIB, or IIIC (without in-transit metastasis) cutaneous melanoma were randomly assigned to receive pembrolizumab at a flat dose of 200 mg (n = 514) or placebo (n = 505) every 3 weeks for 1 year or until disease recurrence or unacceptable toxicity. The two coprimary end points were RFS in the overall population and in those with programmed death-ligand 1 (PD-L1)–positive tumors. RESULTS Pembrolizumab (190 RFS events) compared with placebo (283 RFS events) resulted in prolonged RFS in the overall population (3-year RFS rate, 63.7% v 44.1% for pembrolizumab v placebo, respectively; HR, 0.56; 95% CI, 0.47 to 0.68) and in the PD-L1–positive tumor subgroup (HR, 0.57; 99% CI, 0.43 to 0.74). The impact of pembrolizumab on RFS was similar in subgroups, in particular according to AJCC-7 and AJCC-8 staging, and BRAF mutation status (HR, 0.51 [99% CI, 0.36 to 0.73] v 0.66 [99% CI, 0.46 to 0.95] for V600E/K v wild type). CONCLUSION In resected high-risk stage III melanoma, pembrolizumab adjuvant therapy provided a sustained and clinically meaningful improvement in RFS at 3-year median follow-up. This improvement was consistent across subgroups.

The Use of Adjuvant or Neoadjuvant Chemotherapy in Extremity and Truncal Sarcoma

2018 ◽  
Author(s):  
Robert J Canter
Keyword(s):  
Soft Tissue ◽  
Neoadjuvant Chemotherapy ◽  
Soft Tissue Sarcoma ◽  
Synovial Sarcoma ◽  
Distant Recurrence ◽  
Curative Intent ◽  
Pleomorphic Sarcoma ◽  
Level I ◽  
Meta Analyses ◽  
The Impact

Although neoadjuvant chemotherapy has been an established component of multimodality cancer care for patients with pediatric sarcomas for the past 25 years, the role of adjuvant or neoadjuvant chemotherapy in the management of adult patients with soft tissue sarcoma (STS) amenable to treatment with curative intent remains controversial. Overall, meta-analyses have revealed modest improvements in survival outcomes with the use of adjuvant or neoadjuvant chemotherapy, but individual trials have demonstrated inconsistent results leading some to question the robustness and external validity of the results. A recent randomized trial using anthracycline- and ifosfamide-based chemotherapy has provided further positive evidence in support of neoadjuvant chemotherapy for adult STS patients, but concerns persist regarding the risks of chemotherapy-related toxicities and the generalizability of the findings. Given the substantial risk of distant recurrence and disease-specific death for adult STS patients with tumors greater than 10 cm, especially those with synovial sarcoma and myxoid or round liposarcoma histologies, these patients should be strongly considered for neoadjuvant chemotherapy as part of a combined modality approach. The impact of recent level I data on the broader implementation of adjuvant or neoadjuvant chemotherapy in adult STS remains to be seen.  This review contains 5 figures and 34 references Key Words: chemotherapy, limb salvage, myxoid/round cell liposarcoma, multimodality therapy, soft tissue sarcoma, surgery, survival, synovial sarcoma, undifferentiated pleomorphic sarcoma  

Impact of Smoking History on Pulmonary Metastasis-free Survival in Patients With Soft-tissue Sarcoma

2021 ◽  
Vol 1 (2) ◽  
pp. 89-94
Author(s):  
MASATAKE MATSUOKA ◽  
MASANORI OKAMOTO ◽  
TAMOTSU SOMA ◽  
ISAO YOKOTA ◽  
RYUTA ARAI ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Confidence Interval ◽  
Pulmonary Metastasis ◽  
Hazard Ratio ◽  
Smoking History ◽  
Free Survival ◽  
The Impact

Background/Aim: Although smoking history is predictive of poor pulmonary metastasis-free survival (PMFS) in patients with epithelial tumors, the impact of smoking history on PMFS in those with soft-tissue sarcoma (STS) is not known. Patients and Methods: Patients undergoing treatment for STS at our institutes between 2008 and 2017 were enrolled. Patients were excluded if they had metastatic lesion, or had a histopathological classification demonstrating small round-cell sarcoma. The impact of smoking history on PMFS and overall survival was examined with multivariate analysis using a Cox proportional hazards model. Results: A total of 250 patients were retrospectively reviewed. Patients with smoking history had worse PMFS on multivariate analysis (hazard ratio=2.00, 95% confidence interval=1.12-3.60). On the other hand, smoking history did not significantly affect overall survival (hazard ratio=1.26, 95% confidence interval=0.61-2.58). Conclusion: Patients with STS need to be followed-up by frequent clinical assessments if they have a smoking history.

A Prospective Study Evaluating the Safety and Efficacy of Combination Therapy with Fludarabine Plus Mitoxantrone Followed by Yttrium-90 (90Y) Ibritumomab Tiuxetan (Zevalin®) and Maintenance Rituximab as Front Line Therapy for Patients with Intermediate or High Risk Follicular Non-Hodgkin’s Lymphoma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1360-1360 ◽  
Author(s):  
Stephanie A. Gregory ◽  
Mohamad Kassar ◽  
Henry C. Fung ◽  
Parameswaran Venugopal ◽  
Teresa M. O’Brien ◽  
...  
Keyword(s):  
High Risk ◽  
Prospective Study ◽  
Response Rates ◽  
Stage Iii ◽  
Front Line ◽  
Ibritumomab Tiuxetan ◽  
Safety And Efficacy ◽  
Line Therapy ◽  
The Impact

Abstract Background: The combination of fludarabine and mitoxantrone (FM) as a front line therapy for advanced follicular lymphoma (FL) has been shown to result in higher complete response rates when compared with standard-dose CHOP. We assessed the safety and efficacy of FM followed by 90Y ibritumomab tiuxetan (IT) and maintenance rituximab (MR) in previously untreated patients (pts) with FL. Methods: Pts with newly diagnosed stage III-IV FL and an intermediate or high FLIPI scores were eligible. Pts were required to have an expected survival of at least 3 months, a performance status ≤2, and adequate bone marrow (BM) function (ANC 1500/mm3, platelets 100,000/mm3), liver, and renal function. Initial treatment consisted of 4 cycles of FM (fludarabine 25 mg/m2 on days 1–3, mitoxantrone 12 mg/m2 on day 1 of each 28-day cycle). After restaging, complete and partial responders with ≤25% BM involvement proceeded to the IT therapeutic regimen. Partial responders with >25% BM involvement received 2 additional cycles of FM before IT. The 90Y IT dose (0.3 or 0.4 mCi/kg) was adjusted according to the patient’s platelet count. MR (375 mg/m2 weekly× 4) was scheduled for every 6 months over 2 years. Results: Twenty patients have been enrolled. The median age was 53 years (range: 32–79), and 12 pts were male. 14 pts had stage IV with BM involvement and 6 had stage III. The median FLIPI score was 2 (range, 1–4). Only 1 pt had 6 cycles of FM. At the time of this analysis: 13 pts underwent therapy with IT, 3 of them finished MR cycles, 1 had 3 cycles, 5 had 2 cycles, 1 had 1 cycle, and 3 are still awaiting their first cycle of MR. 7 pts finished FM therapy but still awaiting treatment with IT. Overall response was achieved in 100% of pts; CR in 14/20 pts (70%) and PR in 6/20 pts (30%). The responses to FM were converted from PR to CR in 5 pts: 1 after IT, 1 after 2 cycles of MR, and 3 after completing MR. Grades 3 or 4 hematologic toxicities were encountered in 6/20 pts (30%); with grades 3 or 4 neutropenia in 5 pts (25%) and grades 3 or 4 thrombocytopenia in 5 pts (25%). Platelets, ANC, and hemoglobin nadirs occurred at 3–7 weeks following 90Y IT, and were reversible with median duration of nadirs of 4 weeks (range: 1–5). After median follow up of 16 months (range 3.5 – 39), only one pt developed progressive disease 14 months from registration, and after receiving IT therapy. Repeat BM biopsy at progression showed FL with focal areas of blastoid transformation. No death event has been reported to date. Conclusions: The initial results from this prospective study suggest: 1- FM followed by 90Y ibritumomab tiuxetan and maintenance rituximab regimen is safe and highly effective front line therapy for pts with intermediate or high risk FL (advanced stage with intermediate or high FLIPI scores at diagnosis). 2- The addition of IT and MR to the overall treatment strategy improves the quality of responses; and 3- Though the response rates are encouraging, longer follow-up will be required to evaluate the impact on progression-free survival and overall survival.

Pattern of recurrence after partial and total nephrectomy in non-metastatic renal cell carcinoma (RCC) of low, intermediate and high risk: Implications for follow-up.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 601-601
Author(s):  
Axel Bex ◽  
Yvette Kuijpers ◽  
Allard Noe ◽  
Ruud Bosch ◽  
Simon Horenblas ◽  
...  
Keyword(s):  
High Risk ◽  
Partial Nephrectomy ◽  
Clear Cell ◽  
Local Therapy ◽  
Risk Groups ◽  
Cross Sectional ◽  
Risk Patients ◽  
The Impact ◽  
Metastatic Rcc

601 Background: Guidelines recommend risk-adapted follow-up (FUP) after (partial) nephrectomy in non-metastatic RCC. VEGF-targeted therapy does not cure multiple metastatic RCC. FUP should therefore focus on local recurrences or single-/-oligometastases that may potentially be cured by local therapy. The rate of potentially curable recurrences per risk group is unknown and their pattern and management were analyzed in this study. Methods: From an IRB approved database non-metastatic RCC patients who underwent (partial) nephrectomy from 2004 to 2011 with a minimum FUP of ≥4 years and regular cross-sectional imaging were identified. Risk stratification was assigned to Leibovich- (clear-cell ) or UICC-stage- (non-clear cell) risk groups . Local recurrence, solitary and oligometastases defined as < 3 lesions at a single site were considered potentially curable by local therapy modalities. Recurrences were recorded as was the time to detection of recurrence (TDR) and their management. Results: From 230 patients identified, 191 (clear-cell) and 39 (non-clear cell) were assigned to the Leibovich- or UICC-risk groups respectively. Together, 69 developed recurrences (30 %), of whom 29 (42 %) were potentially curable. Of low-risk patients (32.6 %), only 9 (12 %) had recurrences of which 5 (55.6 %) were potentially curable. In high-risk (19.1 %), of 26 (59.1%) recurrences, the majority were multiple and rapid at a median TDR of 8.4 months (IQR 13.7) with only 6 (23.1 %) potentially curable at a median TDR of 17.6 (IQR 53.8) months. Of 24 recurrences (33.8 %) in intermediate risk, 12 (50 %) potentially curable lesions were detected after a median TDR of 26 (IQR 36.2) months. Together, of 29 potentially curable lesions 15 (51.7 %) were not treated because of comorbidity, poor performance or prognosis and irresectability. Conclusions: High-risk patients predominantly develop multiple metastases early during FUP. A benefit of FUP might derive from identifying potentially curable lesions which develop with latency especially in intermediate and high risk. With only 48 % of potentially curable lesions treated locally the impact of FUP on OS remains controversial.

Does the addition of chemotherapy to neoadjuvant radiotherapy impact survival in high-risk extremity and trunk soft tissue sarcoma?

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 11054-11054
Author(s):  
Mudit Chowdhary ◽  
Akansha Chowdhary ◽  
Neilayan Sen ◽  
Nicholas George Zaorsky ◽  
Kirtesh R. Patel ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Tumor Size ◽  
Primary Site ◽  
High Grade ◽  
Neoadjuvant Radiotherapy ◽  
Cancer Data ◽  
The Impact

11054 Background: Large, high-grade extremity/trunk (ET) non-rhabdomyosarcoma soft-tissue sarcoma (STS) is at high risk for distant recurrence and death. The integration of chemotherapy (C) to standard of care neoadjuvant radiotherapy (RT) remains controversial, even for these patients. This study examines the impact of adding C to neoadjuvant RT on overall survival (OS) in high risk ET-STS. Methods: The National Cancer Data Base (NCDB) was queried for patients ≥18 years with high risk (≥5 cm + high grade) non-rhabdomyosarcoma ET-STS (WHO histology) who received neoadjuvant RT and limb sparing surgery from 2006-2014. Patients were next stratified based upon receipt of C (RT and CRT cohorts). Overall survival (OS) for RT vs CRT cohorts was analyzed using the Kaplan-Meier (KM) method, log-rank test, and Cox proportional hazards models. Propensity score-matched analysis (PSM) was employed to account for potential treatment selection bias between cohorts. Results: A total of 848 (71.1%) and 344 (28.9%) patients received RT and CRT, respectively. Patient cohorts were well-balanced except for the CRT cohort having higher rates of treatment in the West (22.1% vs 10.6%) & Midwest (28.3% vs 22.7%), Charlson-Deyo [CD] score 0 vs ≥1 (85.5% vs 79.4%), younger age (≤50) (45.9% vs 21.7%), synovial sarcoma histology (18.9% vs 3.2%), earlier year of diagnosis (2006-2010) (39.5% vs 32.3%), and positive lymphovascular invasion (2.0 vs 1.51%), (p < 0.05 each). The KM 5-year OS was significantly higher in the CRT vs RT cohort: 69.2% vs 58.1% on univariate (p < 0.0001) and multivariate analysis (Hazard Ratio [HR]: 0.66; 95% Confidence Interval [CI]: 0.52-0.85; p = 0.001) even after adjusting for age, race, income, CD score, histology, tumor size, tumor grade, and primary site (lower extremity; upper extremity; trunk). PSM identified evenly matched cohorts of 300 patients each with respect to age, income, CD score, histology, grade, tumor size, and primary site. The addition of neoadjuvant C remained prognostic for OS on PSM (HR: 0.74 [0.56-0.99], p = 0.042). Conclusions: The addition of C to neoadjuvant RT was associated with improved OS in patients with high risk non-rhabdomyosarcoma ET-STS in the NCDB. These hypothesis generating results support prospective evaluation.

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