Prognostic significance of a positive microscopic margin in high-risk extremity soft tissue sarcoma: implications for management.

1996 ◽  
Vol 14 (2) ◽  
pp. 473-478 ◽  
Author(s):  
M J Heslin ◽  
J Woodruff ◽  
M F Brennan
Keyword(s):  
High Risk ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Cox Model ◽  
Statistical Significance ◽  
Operating Time ◽  
Prognostic Significance ◽  
Rank Test ◽  
High Grade ◽  
Significant Difference

PURPOSE A positive microscopic margin (PMM) is a significant prognostic variable and leads to local recurrence (LR) in high-grade soft tissue sarcoma (STS) patients. Its effect on the rate of distant metastasis (DM) and tumor mortality (TM) remains controversial. PATIENTS AND METHODS One hundred sixty-eight primary, high-risk (high-grade, deep, > or = 5 cm) extremity STS patients were identified from our data base, of which 42 had a PMM. Limb-sparing surgery (LSS) was the primary surgical therapy in 144 patients; 24 received amputation (AMP). Statistical analysis was by log-rank test and Cox model. Significance was defined as a P value less than .05. RESULTS A PMM was a significant negative prognostic factor for both DM and TM (P = .002 and .002, respectively). However, those patients who received LSS with 28% PMMs showed no significant difference in the rate of DM or TM compared with patients who received AMP with only 8% PMMs (log-rank, P = .057 and .28, respectively). A PMM was significantly associated with > or = 1,000 mL blood loss and more than 3 hours of operating time (P < .006 and .001, respectively). CONCLUSION The strong statistical significance that relates a PMM to DM and TM in high-risk STS of the extremity is likely related to biologically aggressive tumors and LSS. Residual microscopic disease is not a guarantee of LR. The main problem in this group of patients is not LR, but DM and subsequent death. Therefore, to increase a disability with further surgery or amputate a patient's limb without clear evidence of LR in this group at high risk for distant recurrence is not recommended.

Adjuvant Therapy for Soft Tissue Sarcoma

2005 ◽  
Vol 3 (2) ◽  
pp. 207-213 ◽  
Author(s):  
Scott M. Schuetze ◽  
Michael E. Ray
Keyword(s):  
Overall Survival ◽  
Radiation Therapy ◽  
High Risk ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Survival Rates ◽  
Wide Resection ◽  
High Grade ◽  
Postoperative Radiation Therapy ◽  
Increased Risk

Wide surgical excision is the backbone of therapy for localized soft tissue sarcoma and often produces excellent results. Patients with a marginal resection of disease and high-grade or large tumors are at an increased risk of recurrence. Radiation therapy (external beam or brachytherapy) has been shown to reduce the risk of local recurrence of disease and should be offered to patients with large (>5 cm) or high-grade sarcomas, especially if a wide resection cannot be performed. Use of preoperative versus postoperative radiation therapy should be planned, in consultation with a radiation oncologist and a surgical oncologist, before resection of the sarcoma if possible. Chemotherapy using an anthracycline- and ifosfamide-based regimen may improve disease-free and overall survival rates. Chemotherapy appears to be most beneficial for patients with very large (≥10 cm), high-grade sarcomas of the extremity who are at a high risk of experiencing distant recurrence of disease. The effect of adjuvant chemotherapy on overall survival remains controversial. Research is greatly needed to identify the patients who are most likely to benefit from conventional chemotherapy, improve the treatment of retroperitoneal sarcomas, and identify novel agents that may impact the natural history of high-risk soft tissue sarcoma.

Pharmacokinetic analyses of vorinostat in patients with metastatic soft tissue sarcoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10041-10041 ◽  
Author(s):  
Thomas Schmitt ◽  
Bianca Andres ◽  
Lu Liu ◽  
Margarete Leisen ◽  
Anthony D Ho ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Half Life ◽  
Mononuclear Cells ◽  
Statistical Significance ◽  
Rank Test ◽  
Open Label ◽  
Time Curve ◽  
Peripheral Blood Mononuclear ◽  
Metastatic Soft Tissue Sarcoma

10041^ Background: New treatment options for patients with metastatic soft tissue sarcoma (STS) are urgently needed. Preclinical studies suggest activity of vorinostat (V), a histone desacetylase (HDAC) inhibitor, in STS. Methods: We initiated a multicenter, open-label, non-randomized phase II trial (SAHA-I, NCT00918489) to investigate efficacy and safety of V in patients with metastatic STS failing 1°-line anthracycline-based CTX. Patients were treated with V 400 mg po QD for 28 days followed by a therapy-free period of 7 days. Blood samples for pharmacokinetic (PK) analyses were collected on day 7 of treatment cycle 1. Samples were acquired before and 30, 60, 90, 120, 240, 360, and 480 minutes after oral administration of V. Plasma- and intracellular concentration of V in peripheral blood mononuclear cells (PBMCs) was determined by mass spectrometry. Statistical differences were assessed by Wilcoxon matched-pairs signed rank test. This trial is ongoing. Results: Data on PK was available for n=8 subjects (male=4, female=4, median age=62 years). In plasma samples, mean Cmax (maximum concentration), tmax (time to reach max. concentration), AUC (area under the plasma-concentration time curve), t1/2 (elimination half-life) and Cl/F (apparent total clearance) were 350 ng/mL, 101 min, 71.1 min*µg/mL, 103 min and 5903 mL/min. The corresponding parameters in PBMCs were 558 ng/mL, 97.5 min, 208.4 min*µg/mL, 286 min and 2475 mL/min, respectively.The AUC plasma/PBMC ratio was 2.93, indicating accumulation of V in PBMCs. Differences in AUC (p=.008) and t1/2 (p=.01) reached statistical significance. Conclusions: Interestingly, significantly higher concentrations of V were achieved in PBMCs andelimination half-life was prolonged compared to plasma. These results suggest potent intracellular activity of V.

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.

Refinement of clinicopathologic staging for localized soft tissue sarcoma of the extremity: a study of 423 adults.

1992 ◽  
Vol 10 (8) ◽  
pp. 1317-1329 ◽  
Author(s):  
J J Gaynor ◽  
C C Tan ◽  
E S Casper ◽  
C F Collin ◽  
C Friedrich ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Local Recurrence ◽  
Soft Tissue Sarcoma ◽  
Distant Metastasis ◽  
Prognostic Value ◽  
Cox Model ◽  
Metastatic Spread ◽  
Outcome Variable ◽  
High Grade ◽  
Clinicopathologic Staging

PURPOSE The prognostic value of factors used in clinicopathologic staging of localized soft tissue sarcoma (STS) of the extremity were analyzed comprehensively. PATIENTS AND METHODS Four hundred twenty-three patients with STS that was confined to the extremity were admitted to Memorial Sloan-Kettering Cancer Center from 1968 to 1978. Cox models for the hazards rates of tumor mortality, development of a distant metastasis, strictly local recurrence, and postmetastasis survival were developed. Tests of changes in the prognostic value of the important variables over time were performed, as well as an analysis of the effect of a local recurrence on the hazard rate of distant metastasis. RESULTS Three unfavorable characteristics contained independent prognostic value for the rates of distant metastasis and tumor mortality: high grade (P less than .00001), deep location (P less than .0002), and size greater than or equal to 5 cm (P less than .007). Their Cox model coefficients did not differ significantly (P greater than or equal to .65); thus, a staging scheme based on the risk of ever developing a distant metastasis would assign equal prognostic weights to grade, depth, and size. The tumor grade effect during the initial 18 months was much larger in magnitude than those for depth and size, and its effect disappeared beyond that time (P = .0003). Thus, a staging scheme based on the risk of early metastatic spread would assign a distinctly larger prognostic weight to grade and lesser but equal weights to depth and size. There was no local recurrence effect on the rate of distant metastasis in the high-risk group (high grade, deep, and greater than or equal to 5 cm; P = .75), but there was a significant association among the remaining groups combined (P = .0039). The magnitude of this association actually increased according to the number of favorable characteristics presented (P = .0024). CONCLUSIONS The refinement of clinicopathologic staging may depend on the choice of outcome variable: ultimate prognosis versus early metastatic spread. Additionally, the observed local recurrence effect may be explained by a tendency for some patients to acquire one or more unfavorable risk factors at the time of local recurrence.

Adjuvant Radiation for Stage II-B Soft Tissue Sarcoma of the Extremity

2002 ◽  
Vol 20 (6) ◽  
pp. 1643-1650 ◽  
Author(s):  
Kaled M. Alektiar ◽  
Dennis Leung ◽  
Michael J. Zelefsky ◽  
Murray F. Brennan
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Local Control ◽  
Tumor Location ◽  
Stage Ii ◽  
External Beam Radiation ◽  
Adjuvant Radiation ◽  
High Grade ◽  
Unplanned Excision ◽  
Significant Difference

PURPOSE: Adjuvant radiation therapy (RT) has been shown to improve local control in patients with high-grade soft tissue sarcoma (STS) of the extremity. This study sought to define the optimal management in patients with stage II-B (high-grade, size ≤ 5 cm) tumors. PATIENTS AND METHODS: Between July 1982 and December 1998, 204 adult patients with primary stage II-B STS underwent limb-sparing surgery with negative microscopic margins. Eighty-eight patients (43%) received RT; 116 (57%) did not. The RT and no-RT groups were balanced with regard to age, site (upper v lower extremity), whether patients had prior unplanned excision, and location (central, ie, shoulder/groin v noncentral). The RT group had more deep tumors (P = .03). Adjuvant RT was delivered with brachytherapy in 60% and external-beam radiation in 40% of patients. RESULTS: With a median follow-up of 67 months, the 5-year local control, distant relapse-free survival, and disease-specific survival rates were 82%, 80%, and 88%, respectively. There was no significant difference in local control between the RT and no-RT groups (84% v 80%, respectively, P = .3). Tumor depth, site, and prior unplanned excision did not correlate with local control. The only independent predictors of poor local control were central tumor location (relative risk [RR] = 3; 95% confidence interval [CI], 2 to 7; P = .005) and age more than 50 years (RR = 6; 95% CI, 2 to 13; P = .001). CONCLUSION: In this retrospective study, adjuvant RT did not significantly improve local control in patients with stage II-B STS of the extremity. The outcome of patients with central tumor location was poor, and efforts to identify the optimal local treatment approach for such patients are warranted.

scholarly journals Clinical and prognostic significance of CD34 expression in bone marrow biopsies in myelodysplastic syndrome

2010 ◽  
Vol 63 (7-8) ◽  
pp. 487-491
Author(s):  
Aleksandar Savic ◽  
Nebojsa Rajic ◽  
Nada Vlaisavljevic ◽  
Vesna Cemerikic-Martinovic ◽  
Stevan Popovic
Keyword(s):  
Bone Marrow ◽  
High Risk ◽  
Statistical Significance ◽  
Prognostic Significance ◽  
Low Risk ◽  
Control Group ◽  
Bone Marrow Biopsies ◽  
Significant Difference ◽  
Risk Patients ◽  
Cd34 Expression

Introduction. The expression of CD34 antigen is increased in a substantial portion of MDS patients, particularly in high risk patients, which was associated with unfavorable survival in some studies. The aim of this study was to determine the CD34 expression in bone marrow biopsies and its prognostic significance in MDS patients and to analyze it in the context of different clinical, laboratory and prognostic parameters. Material and methods. The study was conducted in 53 MDS patients and 20 controls with normal bone marrow. The CD34 expression was determined by CD34 monoclonal antibody and labelled streptovidin biotin peroxidase method. The positivity was determined by counting the 500 cells and it was expressed as percentage. Results. Among the 53 MDS patients there were 37 males and 16 females with average age of 62. The average CD34 expression in the MDS group was 1.37%, the range being 0-8.8%, and in the control group 0.78%, the range being 0-1.60%. The difference was statistically significant (p<0.05). There was a statistically significant difference in the CD34 expression comparing RA and CMML group and high risk and low risk MDS (p<0.02). The median survival in the patients with the CD34 expression with less than 2% was 22 months, while it was 6 months in the patients with the CD34 expression over 2% (p<0.05). In a multivariate analysis the CD34 expression together with the karyotype and transfusion dependence had a statistical significance (p<0.05). Conclusion. The CD34 expression in bone marrow biopsies is higher in the MDS patients comparing with the controls as well as in high risk comparing with low risk patients. The cutoff 2% seems to have a prognostic significance.

scholarly journals Retropubic, laparoscopic, and robot-assisted radical prostatectomy: a multi-institutional comparative study

2020 ◽  
Vol 26 (1) ◽  
Author(s):  
Amr A. Faddan ◽  
Mahmoud M. Shalaby ◽  
Mohamed Gadelmoula ◽  
Younis Alshamsi ◽  
Daniar K. Osmonov ◽  
...  
Keyword(s):  
Radical Prostatectomy ◽  
Complication Rate ◽  
Perioperative Complications ◽  
Statistical Significance ◽  
Operating Time ◽  
Perioperative Outcomes ◽  
Academic Institutions ◽  
Robot Assisted ◽  
Surgical Specimen ◽  
Significant Difference

Abstract Background The standard surgical treatment of localized prostate cancer (PCa) has been rapidly changed along the last two decades from open to laparoscopic and finally robot-assisted techniques. Herein, we compare the three procedures for radical prostatectomy (RP), namely radical retropubic (RRP), laparoscopic (LRP), and robot-assisted laparoscopic (RALRP) regarding the perioperative clinical outcome and complication rate in four academic institutions. Methods A total of 394 patients underwent RP between January 2016 and December 2018 in four academic institutions; their records were reviewed. We recorded the patient age, BMI, PSA level, Gleason score and TNM stage, type of surgery, the pathological data from the surgical specimen, the perioperative complications, unplanned reoperating, and readmission rates within 3 months postoperatively. Statistical significance was set at (P < 0.05). All reported P values are two-sided. Results A total of 123 patients underwent RALRP, 220 patients underwent RRP, and 51 underwent LRP. There was no statistically significant difference between the three groups regarding age, BMI, prostatic volume, and preoperative PSA. However, there were statistically significant differences between them regarding the operating time (P < .0001), catheterization period (P < .001), hospital stay (P < .0001), and overall complications rate (P = .023). Conclusions The minimally invasive procedures (RALRP and LRP) are followed by a significantly lower complication rate. However, the patients’ factors and surgical experience likely impact perioperative outcomes and complications.

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