Pathologic complete response and survival outcomes in patients with localized soft tissue sarcoma treated with neoadjuvant chemoradiotherapy or radiotherapy: Long-term update of NRG Oncology RTOG 9514 and 0630.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 11012-11012 ◽  
Author(s):  
Dian Wang ◽  
Jonathan Harris ◽  
William G. Kraybill ◽  
Burton Larry Eisenberg ◽  
David G. Kirsch ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Pathologic Complete Response ◽  
Neoadjuvant Chemoradiotherapy ◽  
Complete Response ◽  
Hazard Ratio ◽  
Survival Outcomes ◽  
Phase Ii Trials ◽  
P Values

11012 Background: We sought to determine the prognostic significance of pathologic complete response (pCR) in soft tissue sarcoma (STS) in patients (pts) receiving neoadjuvant chemoradiotherapy (RTOG 9514) or radiotherapy (RTOG 0630) with long-term outcomes. Methods: RTOG has completed two phase II trials (RTOG 9514 and RTOG 0630) for pts with localized STS. Pts with high-grade STS ≥8 cm of extremities or body wall were enrolled to 9514 from 1997-2000 and received 3 cycles neoadjuvant chemotherapy (CT), interdigitated with RT, and 3 cycles postop CT. Pts with STS of extremities were enrolled to 0630 from 2008-2010 and received preoperative RT without CT. One pathology expert (DL) assessed pts for pCR at time of surgery without knowledge of disease outcomes. Overall and disease-free survival (OS and DFS) were calculated from the date of surgery. Pts that did not have surgery or had an amputation were excluded. Hazard ratios (HR) and p-values were estimated by multivariate Cox model stratified by study, where possible (i.e., > 0 events in both groups); otherwise p-values were calculated by stratified log-rank test. Results: Of 135 who had surgery, 123 were evaluable for pCR: 14/51 (27.5%) on 9514 and 14/72 (19.4%) on 0630 had pCR. With median follow-up of > 5 years for surviving pts, OS is 100% for pts with pCR vs. 5-year 76.5% (95% confidence interval 62.3-90.8) and 56.4% (43.3-69.5) for pts with < pCR in 9514 and 0630, respectively. pCR is associated with improved OS (p = 0.01) and DFS [HR 4.91 (1.51-15.93); p = 0.008] relative to < pCR. Local failure rate was 0% in pts with pCR vs. 5-year 11.7% (3.6-25.1) and 9.1% (3.3-18.5) for pts with < pCR in 9514 and 0630, respectively. Leiomyosarcoma/liposarcoma/myxofibrosarcoma are associated with better OS [hazard ratio 2.24 (1.12 and 4.45)] while liposarcoma/myxofibrosarcoma are associated with better DFS [hazard ratio 2.42 (1.23-4.76)]. Conclusions: Results from this analysis have demonstrated that pCR is associated with improved survival outcomes in pts with STS treated with either neoadjuvant RT or CT-RT. pCR should be considered as a survival surrogate for future STS studies. Clinical trial information: RTOG 9514 and RTOG 0630.

scholarly journals Evaluation of Pathologic Complete Response as a Surrogate for Long-Term Survival Outcomes in Triple-Negative Breast Cancer

2020 ◽  
Vol 18 (8) ◽  
pp. 1096-1104
Author(s):  
Min Huang ◽  
Joyce O’Shaughnessy ◽  
Jing Zhao ◽  
Amin Haiderali ◽  
Javier Cortes ◽  
...  
Keyword(s):  
Triple Negative ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Sensitivity Analyses ◽  
Coefficient Of Determination ◽  
Survival Outcomes ◽  
Term Survival ◽  
Long Term Survival

Background: Pathologic complete response (pCR) is a common efficacy endpoint in neoadjuvant therapy trials for triple-negative breast cancer (TNBC). Previous studies have shown that pCR is strongly associated with improved long-term survival outcomes, including event-free survival (EFS) and overall survival (OS). However, the trial-level associations between treatment effect on pCR and long-term survival outcomes are not well established. This study sought to evaluate these associations by incorporating more recent clinical trials in TNBC. Methods: A literature review identified published randomized controlled trials (RCTs) of neoadjuvant therapy for TNBC that reported results for both pCR and EFS/OS. Meta-regression models were performed to evaluate the association of treatment effect on pCR and EFS/OS. Sensitivity analyses were conducted to assess the impact of divergent study designs. Results: Ten comparisons from 8 RCTs (N=2,478 patients) were identified from the literature review. The log (odds ratio) of pCR was a significant predictor of the log (hazard ratio) of EFS (P=.003), with a coefficient of determination of 0.68 (95% CI, 0.41–0.95). There was a weaker association between pCR and OS (P=.18), with a coefficient of determination of 0.24 (95% CI, 0.01–0.77). Consistent results were found in the exploratory analysis and sensitivity analyses. Conclusions: This is the first study that has shown a trial-level association between pCR and survival outcomes in TNBC. By incorporating the most up-to-date RCTs, this study showed a significant trial-level association between pCR and EFS. A positive association between pCR and OS was also recorded.

Defects in DNA repair genes and long-term survival in cisplatin-based neoadjuvant chemotherapy for muscle invasive bladder cancer (MIBC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4536-4536
Author(s):  
Benjamin Miron ◽  
Eric A. Ross ◽  
Fern Anari ◽  
John O'Neill ◽  
Jean H. Hoffman-Censits ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Phase Ii ◽  
Pathologic Complete Response ◽  
Predictive Biomarkers ◽  
Complete Response ◽  
Phase Ii Trials ◽  
Two Phase ◽  
Term Survival

4536 Background: Although cisplatin-based neoadjuvant chemotherapy (NAC) has demonstrated an overall survival (OS) benefit in MIBC, only a subset of patients have pathologic complete response (pT0) at cystectomy. ATM, RB1 and FANCC mutations have shown correlation with pT0 to cisplatin-based NAC, as previously published. We now report updated OS and disease specific survival (DSS) from two phase II trials using these gene alterations as biomarkers. Methods: Patients with stage T2-T4 (N0 or N1) MIBC were enrolled in phase II trials of dose-dense NAC with MVAC (methotrexate, vinblastine, adriamycin, and cisplatin; NCT01031420) or GC (gemcitabine and cisplatin; NCT01611662). Patients were treated with NAC with plan for curative cystectomy. DNA from pretreatment tumor tissue was sequenced for coding exons of 287 cancer-related genes and analyzed for mutations. Survival in patients with one or more mutations in ATM, RB1, or FANCC genes was compared to those without mutations. Results: Of 58 pts treated, 38% (22/58 pts) had relevant mutations in the combined group of MVAC (13/34 pts) and GC (9/24 pts) trials. At a median follow-up of 56 months and minimum follow up of 16 months, patients with mutations had statistically significantly greater OS (p = 0.0043) and DSS (p = 0.0015). Median OS/DSS was not reached for patients with a mutation in any group. At 5 years post treatment, OS/DSS were greater in mutated vs non-mutated patients in all groups (see table). Conclusions: Long-term follow up reveals that previously reported improved responses to cisplatin-based NAC associated with mutations in ATM, RB1 and FANCC also confer a clinically meaningful and statistically significant survival benefit in these patients. These alterations may be useful as predictive biomarkers to allow clinicians to prioritize patients most likely to benefit from NAC prior to radical cystectomy. [Table: see text]

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.

scholarly journals Targeted treatment with pazopanib in metastatic soft tissue sarcoma: Nearly complete response in two cases

2014 ◽  
Vol 3 (2) ◽  
pp. 400-402 ◽  
Author(s):  
ALI MURAT SEDEF ◽  
FATIH KÖSE ◽  
ÖZLEM DOĞAN ◽  
TARKAN ERGÜN ◽  
AHMET SEZER ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Complete Response ◽  
Targeted Treatment ◽  
Metastatic Soft Tissue Sarcoma
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