Histologic Subtype Defines the Risk and Kinetics of Recurrence and Death for Primary Extremity/Truncal Liposarcoma.

OBJECTIVE: We sought to define the prognostic significance of histologic subtype for extremity/truncal liposarcoma (LPS). BACKGROUND: LPS, the most common sarcoma, is comprised of 5 histologic subtypes. Despite their distinct behaviors, LPS outcomes are frequently reported as a single entity. METHODS: We analyzed data on all patients from a single-institution prospective database treated from July 1982 to September 2017 for primary, nonmetastatic, extremity or truncal LPS of known subtype. Clinicopathologic variables were tested using competing risk analyses for association with disease-specific death (DSD), distant recurrence (DR), and local recurrence (LR). RESULTS: Among 1001 patients, median follow-up in survivors was 5.4 years. Tumor size and subtype were independently associated with DSD and DR. Size, subtype, and R1 resection were independently associated with LR. DR was most frequent among pleomorphic and round cell LPS; the former recurred early (43% by 3 years), and the latter over a longer period (23%, 3 years; 37%, 10 years). LR was most common in dedifferentiated LPS, in which it occurred early (24%, 3 years; 33%, 5 years), followed by pleomorphic LPS (18%, 3 years; 25%, 10 years). CONCLUSIONS: Histologic subtype is the factor most strongly associated with DSD, DR, and LR in extremity/truncal LPS. Both risk and timing of adverse outcomes vary by subtype. These data may guide selective use of systemic therapy for patients with round cell and pleomorphic LPS, which carry a high risk of DR, and radiotherapy for LPS subtypes at high risk of LR when treated with surgery alone.

Outcome of 1000 Patients With Gastrointestinal Stromal Tumor (GIST) Treated by Surgery in the Pre- and Post-imatinib Eras.

OBJECTIVE: To characterize the results of surgery for gastrointestinal stromal tumor (GIST) in the pre and post-imatinib eras at a single institution and to identify current prognostic clinicopathologic factors. BACKGROUND: Imatinib has radically changed the management of GIST, yet the magnitude of impact on outcome across the spectrum of GIST presentation and relevance of historical prognostic factors are not well defined. METHODS: We retrospectively analyzed 1000 patients who underwent surgery for GIST at our institution from 1982 to 2016. Patients were stratified by presentation status as primary tumor only (PRIM), primary with synchronous metastasis (PRIM + MET), or metachronous recurrence/metastases (MET), and also imatinib era (before and after it became available). Cox proportional-hazard models and Kaplan-Meier methods were used to model and estimate overall survival (OS) and recurrence-free survival (RFS). RESULTS: OS was longer in the imatinib era compared with the pre-imatinib era in each presentation group, including in Miettinen high-risk primary tumors. Among PRIM patients from the pre-imatinib era, tumor site, size, and mitotic rate were independently associated with OS and RFS on multivariate analysis. PRIM patients in the imatinib era who received imatinib (neoadjuvant and/or adjuvant) had higher risk tumors, but after adjusting for treatment, only size >10 cm remained independently prognostic of RFS [hazard ratio (HR) 3.85, 95% confidence interval (CI) 2.00-7.40, P < 0.0001) and OS (HR 3.37, 95% CI 1.60-7.13, P = 0.001)]. CONCLUSIONS: Patients treated in the imatinib era had prolonged OS across all presentations. In the imatinib era, among site, size, and mitotic rate, high-risk features were associated with treatment with the drug, but only size >10 cm correlated with outcome. Imatinib should still be prescribed for patients with high-risk features.

Optimal Percent Myxoid Component to Predict Outcome in High-Grade Myxofibrosarcoma and Undifferentiated Pleomorphic Sarcoma.

BACKGROUND: Myxofibrosarcoma and undifferentiated pleomorphic sarcoma (UPS) are aggressive, genetically complex sarcomas. The minimum myxoid component used as a criterion for myxofibrosarcoma varies widely, so we determined the optimal myxoid component cutpoints for stratifying outcomes of UPS and myxofibrosarcoma. We also analyzed clinicopathologic factors associated with outcome. METHODS: Review of a prospective, single-institution database identified 197 patients with primary, high-grade extremity/truncal myxofibrosarcoma or UPS resected during 1992-2013. Histology was reviewed and percent myxoid component determined for each tumor. Disease-specific survival (DSS) and distant recurrence-free survival (DRFS) were analyzed using the Kaplan-Meier method, log-rank test, and Cox regression. RESULTS: Median follow-up for survivors was 6.4 years. In minimum p value analysis of myxoid component, the best cutpoint for both DSS and DRFS was 5% (adjusted p ≤ 0.001), followed by 70%. Therefore, sarcomas with <5% myxoid component (n = 69) were classified as UPS and those with ≥5% myxoid component (n = 128) as myxofibrosarcoma. Five-year DRFS was 24% for UPS, 51% for 5-69% myxoid component myxofibrosarcoma, and 65% for ≥70% myxoid component myxofibrosarcoma. Myxoid component, tumor size, and age were independently associated with DSS; myxoid component and tumor size were associated with DRFS. Only tumor site was associated with local recurrence. CONCLUSIONS: Percent myxoid component and tumor size are the two most important predictors of DSS and DRFS in high-grade myxofibrosarcoma and UPS. A 5% myxoid component cutpoint is an improved criterion for classifying myxofibrosarcoma. Myxoid component-based classification improves stratification of patient outcome and will aid in selection of patients for systemic therapy and clinical trials.

Prognostic Factors After Neoadjuvant Imatinib for Newly Diagnosed Primary Gastrointestinal Stromal Tumor.

INTRODUCTION: Neoadjuvant imatinib (Neo-IM) therapy may facilitate R0 resection in primary gastrointestinal stromal tumors (GISTs) that are large or in difficult anatomic locations. While response to preoperative tyrosine kinase inhibitors is associated with better outcome in metastatic GIST, little is known about prognostic factors after Neo-IM in primary GIST. STUDY DESIGN: Patients with primary GIST with or without synchronous metastases who underwent Neo-IM were retrospectively analyzed from a prospective maintained institutional database for Response Evaluation Criteria in Solid Tumors (RECIST), tumor viability, and mitotic rate. Overall survival (OS) was estimated by Kaplan-Meier and compared by log-rank test. Cox proportionate hazard models were used for univariate and multivariate analysis. RESULTS: One hundred and fifty patients were treated for a median of 7.1 months (range 0.2-160). By RECIST, partial response, stable disease, and progressive disease were seen in 40%, 51%, and 9%, respectively. By pathologic analysis, ≤ 50% of the tumor was viable in 72%, and the mitotic rate was ≤ 5/50HPF in 74%. On multivariate analysis, RECIST response and tumor viability were not associated with OS, while post-treatment high mitotic rate (hazard ratio (HR) for death 5.3, CI 2.3-12.4), R2 margins (HR 6.0, CI 2.3-15.5), and adjuvant imatinib (HR 0.4, CI 0.2-0.9) were (p < 0.05). Five-year OS was 81 vs. 38% for low vs. high mitotic rate; 81, 59, and 39% for R0, R1, and R2 margins; and 75 vs 61% for adjuvant vs. no adjuvant imatinib therapy (p < 0.05). CONCLUSIONS: In primary GIST undergoing Neo-IM therapy, progression was uncommon, but substantial down-sizing occurred in the minority. High tumor mitotic rate and incomplete resection following Neo-IM were associated with poor outcome, while adjuvant imatinib was associated with prolonged survival.

Primary anatomical site, adjuvant therapy, and other prognostic variables for dedifferentiated liposarcoma.

BACKGROUND: Dedifferentiated liposarcoma (DDLPS) is a high-grade, clinically aggressive tumor associated with low survival probabilities. Prognostic variables for DDLPS have not been previously reported in a large patient population. METHODS: A total of 3573 patients with primary DDLPS were analyzed from the National Cancer Data Base (NCDB). The 5- and 10-year survival probabilities were calculated, and the groups were compared using log-rank comparisons and multivariable Cox hazard regression analysis. Median survival was also calculated. RESULTS: Males comprised 65% of the cohort, the median age at diagnosis was 64 years of age, and 65.4% of the patients were between 51 and 75 years of age. The most common site for primary tumors is the retroperitoneum or abdomen (59.5%). Head or neck tumors had the best 5-year outcomes (86.4%) followed by extremities (67.1%), pelvis (65.8%), thorax or trunk (58.9%), and finally retroperitoneum or abdomen (42.6%). Best outcomes were noted in the 26- to 50-year-old age group (5-year survival:66.8%), < 10 cm size (5-year survival:66.1%), FNCLCC grade 1 (5-year survival:69.2%), and stage II disease (5-year survival:66.7%). Radiation therapy yielded the best 5-year and 10-year survival probabilities of 59% and 39.3%, respectively. Out of all the adjuvant therapies, the use of radiation resulted in the best 5-year survival of 63.4%. CONCLUSION: In the largest and most comprehensive study to date on DDLPS, major findings include primary site as a significant prognostic variable with age at presentation, sex, tumor stage, and type of adjuvant therapy significantly impacting overall survival.

Treatment Facility: An Important Prognostic Factor for Dedifferentiated Liposarcoma Survival.

A National Cancer Database study of on survival outcomes for patients with dedifferentiated liposarcomas found that insurance status, median household income, and treatment facility were associated with differences in median survival and 5- and 10-year survival probabilities.

The epidemiology and survivorship of clear cell sarcoma: a National Cancer Database (NCDB) review.

PURPOSE: Clear cell sarcoma (CCS) is a rare soft tissue tumor thought to originate from tendons and aponeuroses. This is the largest and most comprehensive study of CCS to the best of our knowledge. In addition, this is the first study to determine the estimated 10-year overall survival, specific treatment modalities including neoadjuvant and adjuvant combinations, and sites of distant metastasis in CCS utilizing a national database. METHODS: The National Cancer Database (NCDB) was used to study 489 patients diagnosed with CCS from 2004 to 2014. Kaplan-Meier methods were used to estimate 5- and 10-year overall survival, and log-rank tests were used to compare survival amongst stage. RESULTS: Median age at diagnosis was 39 years. Males and females were equally affected. Race distribution was 78% Caucasian and 15% Black. Most common primary site was lower limb or hip (53%). Percentage of patients with distant organ metastases was 15%, with lung being the most common site (4%). Median overall survival was 57.2 months. Overall estimated 5- and 10-year survival was approximately 50 and 38%, respectively. Approximate 5-year survival for Stages I-IV was 75, 65, 35, and 15%, respectively. Stages at disease presentation were 34% at Stage I, 13% at Stage II, 16% at Stage III, and 38% at Stage IV. Surgery was the most common form of treatment (83%); 34% received radiation and 20% received chemotherapy. CONCLUSION: The 5-year overall survival for CCS in Stages III and IV was much worse than Stages I and II. Overall estimated 5- and 10-year survival was approximately 50 and 38%, respectively. Men and women were equally affected and had a median age at diagnosis of 39 years. The most common tumor location was lower limb and hip and the most common site of metastases was the lung.

Biomarkers for early detection of ovarian cancer.

Ovarian cancer is the most lethal gynecological malignancy. However, effective screening strategies have not been established and continue to be elusive. A good screening test must adequately address validity, reliability, yield, cost, acceptance and follow-up services. An ideal screening test for ovarian cancer must have a high sensitivity in order to correctly diagnose all women with the disease and a high specificity to avoid false-positive results. The current screening modalities of bimanual examination, CA-125 and transvaginal ultrasonography together allow us to detect only 30-45% of women with early-stage disease. Recent developments in proteomic and genomic research have identified a number of potential biomarkers. Although panels of tumor markers and proteomic-based technologies may improve the positive predictive value, all markers require validation and interfacing with newly developed diagnostic imaging technologies. While a large amount of information on miRNAs has been promising, much remains to be elucidated. This review will examine the current status of biomarkers and technologies of interest in the effort of early detection of ovarian cancer.