18 results on '"Nicole, Moraco"'
Search Results
2. Soft tissue sarcoma of the head & neck: Nomogram validation and analysis of staging systems
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Andrew G. Shuman, Nicole Moraco, Deborah Kuk, Murray F. Brennan, Samuel Singer, Jatin P. Shah, Frank L. Palmer, and Snehal G. Patel
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medicine.medical_specialty ,genetic structures ,business.industry ,Concordance ,Soft tissue sarcoma ,Head and neck cancer ,Head neck ,Soft tissue ,General Medicine ,Nomogram ,medicine.disease ,Surgery ,Oncology ,Quartile ,Overall survival ,Medicine ,Radiology ,business - Abstract
Background and Objectives Soft tissue sarcomas of the head and neck (STSHN) comprise a rare group of malignancies. Our objective is to determine the utility of soft tissue sarcoma staging systems within the head and neck, and to validate an individualized soft tissue sarcoma nomogram within head and neck primary sites. Methods Previously-untreated patients with STSHN diagnosed and treated between 1982 and 2012 were eligible (n = 319, median follow-up 46 months). Clinical variables were extracted from a prospectively-maintained database. The performance of AJCC/UICC and MSK staging systems and a soft tissue sarcoma-specific nomogram were assessed. Results Four-year overall survival (OS), disease specific survival (DSS), and recurrence-free survival (RFS) were 72%, 76%, and 71%, respectively. AJCC/UICC and MSK staging systems accurately stratified outcomes (OS, DSS, and RFS; P
- Published
- 2015
3. Histology-based Classification Predicts Pattern of Recurrence and Improves Risk Stratification in Primary Retroperitoneal Sarcoma
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Murray F. Brennan, Cristina R. Antonescu, Li-Xuan Qin, Narasimhan P. Agaram, Nicole Moraco, Deborah Kuk, Samuel Singer, Marcus C.B. Tan, and Aimee M. Crago
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Leiomyosarcoma ,Male ,medicine.medical_specialty ,Solitary fibrous tumor ,Liposarcoma ,Risk Assessment ,Article ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Adjuvant therapy ,Humans ,Cumulative incidence ,Prospective Studies ,Retroperitoneal Neoplasms ,Prospective cohort study ,Survival rate ,Aged ,business.industry ,Incidence ,Age Factors ,Sarcoma ,Nomogram ,Middle Aged ,medicine.disease ,Prognosis ,Surgery ,Tumor Burden ,Survival Rate ,030220 oncology & carcinogenesis ,030211 gastroenterology & hepatology ,Female ,Radiology ,Neoplasm Recurrence, Local ,business ,Follow-Up Studies - Abstract
OBJECTIVE To determine the prognostic significance of histologic type/subtype in a large series of patients with primary resected retroperitoneal sarcoma. BACKGROUND The histologic diversity and rarity of retroperitoneal sarcoma has hampered the ability to predict patient outcome. METHODS From a single-institution, prospective database, 675 patients treated surgically for primary, nonmetastatic retroperitoneal sarcoma during 1982 to 2010 were identified and histologic type/subtype was reviewed. Clinicopathologic variables were analyzed for association with disease-specific death (DSD), local recurrence (LR), and distant recurrence (DR). RESULTS Median follow-up for survivors was 7.5 years. The predominant histologies were well-differentiated liposarcoma, dedifferentiated liposarcoma, and leiomyosarcoma. Five-year cumulative incidence of DSD was 31%, and factors independently associated with DSD were R2 resection, resection of 3 or more contiguous organs, and histologic type. Five-year cumulative incidence for LR was 39% and for DR was 24%. R1 resection, age, tumor size, and histologic type were independently associated with LR; size, resection of 3 or more organs, and histologic type were independently associated with DR. Liposarcoma and leiomyosarcoma were associated with late recurrence and DSD (as long as 15 years from diagnosis). For solitary fibrous tumor, LR was uncommon (
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- 2017
4. Lessons Learned From the Study of 10,000 Patients With Soft Tissue Sarcoma
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Cristina R. Antonescu, Murray F. Brennan, Samuel Singer, and Nicole Moraco
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Adult ,Oncology ,Prognostic variable ,medicine.medical_specialty ,Mesenchymal Differentiation ,Databases, Factual ,business.industry ,Soft tissue sarcoma ,MEDLINE ,Soft tissue ,Sarcoma ,medicine.disease ,Article ,Surgery ,Metastasis ,Viscera ,Lymphedema ,Lower Extremity ,Internal medicine ,medicine ,Humans ,Neoplasm Recurrence, Local ,business ,Prior Radiation Therapy - Abstract
The management of rare tumors is difficult because of limited information on natural history. Our objective was to describe a long-term comprehensive prospective database with the assumption that with careful attention to patient, predisposing tumor and treatment variables, valuable knowledge could be obtained that could guide management.In July of 1982, we began a prospective database of all adult patients admitted to our institution for a surgical procedure for soft tissue sarcoma. Patients were included if they had primary, locally recurrent or metastatic disease undergoing a surgical procedure.Over 3 decades, we entered 10,000 patients into our prospective soft tissue sarcoma database. Data were entered on a weekly or biweekly schedule with full participation of a multidisciplinary team and a dedicated sarcoma pathologist. Extensive information is available from this database. In this article, we describe distribution by site, histopathology, sex, size, and grade. We utilize this information along with outcome data for local recurrence, distant recurrence, disease specific, and overall survival. The value of molecular diagnosis is illustrated.Continuous prospective long-term databases are important to obtain knowledge particularly for rare tumors. Such data can be a rich resource for the development of prognostic indicators including nomograms and can be analyzed by Bayesian Belief Networks. These long-term data linked to collection of tumor and germ-line tissue at the time of an initial procedure will remain a resource for future decades.
- Published
- 2014
5. Recurrence Patterns After Resection of Soft Tissue Sarcomas of the Chest Wall
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Valerie W. Rusch, Nicole Moraco, Robert McMillan, Camelia S. Sima, and James Huang
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Adult ,Male ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Adolescent ,Liposarcoma ,Undifferentiated Pleomorphic Sarcoma ,Young Adult ,Humans ,Medicine ,Thoracic Wall ,Aged ,Retrospective Studies ,Aged, 80 and over ,business.industry ,Soft tissue sarcoma ,Hazard ratio ,Soft tissue ,Sarcoma ,Retrospective cohort study ,Middle Aged ,medicine.disease ,Surgery ,medicine.anatomical_structure ,Female ,Neoplasm Recurrence, Local ,Cardiology and Cardiovascular Medicine ,business ,Thoracic wall - Abstract
Background Soft tissue sarcoma (STS) of the chest wall is uncommon, and our knowledge is limited to small, single institutional case series. Although some series have examined prognostic factors for survival with this rare set of neoplasms, our knowledge of the patterns of relapse is limited. Methods We performed a retrospective review of a prospectively maintained database of consecutive patients treated for STS of the chest wall. Predictors of survival and recurrence were analyzed using Cox and competing-risk regression analyses. Results From 1989 to 2011, 192 patients underwent resection for STS of the chest wall. The most common histopathologic type was desmoid (33 [17%]), followed by undifferentiated pleomorphic sarcoma (32 [16%]), liposarcoma (22 [11%]), and myxofibrosarcoma (22 [11%]). The median follow-up was 50.9 months. The 5- and 10-year survival rates were 73% and 61%, respectively. Recurrences occurred in 45 patients (23%): 17 developed local recurrences, and 28 developed distant recurrences. Among the patients who developed recurrences, the median time to event was 11.6 months for local recurrences and 13.5 months for distant recurrences. The most common histologic type among recurrences was undifferentiated pleomorphic sarcoma (n = 12), and the most common site of distant recurrences was lung (n = 18). The primary treatment modality for both local and distant recurrences was surgical resection; median survival after recurrence was 19.4 months. Conclusions Recurrences of STS are common after surgical resection. Although local or distant recurrences can occur soon after surgery, both can often be treated with resection, producing reasonable outcomes.
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- 2013
6. High-risk features in radiation-associated breast angiosarcomas
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C. R. Antonescu, Ping Chi, R C Carvajal, Mark A. Dickson, William D. Tap, Gary K. Schwartz, Sandra P. D'Angelo, Li-Xuan Qin, Mary Louise Keohan, Deborah Kuk, Samuel Singer, Mrinal M. Gounder, and Nicole Moraco
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Adult ,Cancer Research ,medicine.medical_specialty ,Neoplasms, Radiation-Induced ,medicine.medical_treatment ,Hemangiosarcoma ,Breast Neoplasms ,chemotherapy ,Malignancy ,radiation associated breast angiosarcoma ,Disease-Free Survival ,surgery ,Internal medicine ,medicine ,Humans ,Aged ,Aged, 80 and over ,Chemotherapy ,business.industry ,Incidence (epidemiology) ,Cancer ,Soft tissue ,Neoplasms, Second Primary ,Middle Aged ,Prognosis ,medicine.disease ,Surgery ,radiation ,Radiation therapy ,Treatment Outcome ,Oncology ,Clinical Study ,Radiation associated ,Female ,Radiotherapy, Adjuvant ,Neoplasm Recurrence, Local ,business - Abstract
Background: Radiation-associated breast angiosarcoma (RT-AS) is an uncommon malignancy with an incidence of less than 1 % of all soft tissue sarcomas. The overall prognosis is quite dismal with high rates of recurrences and poor overall survival. There is an obvious paucity of data regarding clinical outcomes of patients with breast RT-AS. Methods: We identified all patients with RT-AS treated at the Memorial Sloan-Kettering Cancer Center between 1982–2011 and collected their correlative clinical information. Results: We identified 79 women with RT-AS with a median age of 68 (range 36–87). The median interval between radiation and development of RT-AS was 7 years (range 3–19). The median time to local and distant recurrence was 1.29 years (95 % CI 0.72–NA) and 2.48 years (95 % CI 1.29–NA), respectively. The median disease-specific survival was 2.97 years (95 % CI 2.21–NA). Independent predictors of worse disease-specific survival included age ⩾68 years (HR 3.11, 95 % CI 1.20–8.08, P=0.020) and deep tumors (HR 3.23, 95 % CI 1.02–10.21, P=0.046.) Conclusion: RT-AS has high local/distant recurrence rates, limited duration on standard chemotherapy and poor disease-specific survival.
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- 2013
7. Predictors of Survival and Recurrence in Primary Leiomyosarcoma
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Li-Xuan Qin, Rebecca A. Gladdy, Samuel Singer, Narasimhan P. Agaram, Murray F. Brennan, and Nicole Moraco
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Adult ,Leiomyosarcoma ,Male ,Oncology ,medicine.medical_specialty ,Lung Neoplasms ,Neoplasm, Residual ,Soft Tissue Neoplasm ,Adolescent ,Bone Neoplasms ,Soft Tissue Neoplasms ,Article ,Young Adult ,Risk Factors ,Surgical oncology ,Internal medicine ,medicine ,Humans ,Retroperitoneal Neoplasms ,Muscle, Skeletal ,Survival analysis ,Aged ,Retrospective Studies ,Aged, 80 and over ,business.industry ,Soft tissue sarcoma ,Liver Neoplasms ,Torso ,Extremities ,Retrospective cohort study ,Middle Aged ,medicine.disease ,Survival Analysis ,Retroperitoneal Neoplasm ,Surgery ,body regions ,Primary Leiomyosarcoma ,Multivariate Analysis ,Female ,Neoplasm Grading ,Neoplasm Recurrence, Local ,business - Abstract
Leiomyosarcoma is a soft tissue sarcoma whose outcome has historically been confounded by the inclusion of gastrointestinal stromal tumors. Thus, we sought to determine the factors that predict survival and recurrence in patients with primary leiomyosarcoma alone.During 1982-2006, a total of 353 patients with primary resectable leiomyosarcoma were identified from a prospective database. Multivariate analysis was used to assess clinicopathologic factors for association with disease-specific survival (DSS). Competing risk survival analysis was used to determine factors predictive for local and distant recurrence.Of 353 patients, 170 (48 %) presented with extremity, 144 (41 %) with abdominal/retroperitoneal, and 39 (11 %) with truncal tumors. Median age was 57 (range, 18-88) years, and median follow-up was 50 (range, 1-270) months. Most tumors were high grade (75 %), deep (73 %), and completely resected (97 %); median size was 6.0 (range, 0.3-45) cm. Abdominal/retroperitoneal location was associated with worse long-term DSS compared to extremity or trunk (P = 0.005). However, by multivariate analysis, only high grade and size were significant independent predictors of DSS. Overall, 139 patients (39 %) had recurrence: 51 % of those with abdominal/retroperitoneal, 33 % of extremity, and 26 % of truncal disease. Significant independent predictors for local recurrence were size and margin, whereas predictors for distant recurrence were size and grade. Site was not an independent predictor of recurrence; however, late recurrence (5 years) occurred in 9 % of abdominal/retroperitoneal and 4 % of extremity lesions.Grade and size are significant independent predictors of DSS and distant recurrence. Long-term follow-up in leiomyosarcoma is important, as late recurrence continues in 6-9 % patients.
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- 2013
8. Oncologic Outcomes of Sporadic, Neurofibromatosis-Associated, and Radiation-Induced Malignant Peripheral Nerve Sheath Tumors
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Nicole Moraco, Samuel Singer, Li-Xuan Qin, Cristina R. Antonescu, Murray F. Brennan, Jennifer LaFemina, Ryan C. Fields, and Aimee M. Crago
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Adult ,Male ,congenital, hereditary, and neonatal diseases and abnormalities ,Pathology ,medicine.medical_specialty ,Neoplasm, Residual ,Neoplasms, Radiation-Induced ,Neurofibromatosis 1 ,Adolescent ,medicine.medical_treatment ,Malignant peripheral nerve sheath tumor ,Kaplan-Meier Estimate ,Article ,Nerve Sheath Neoplasms ,Statistics, Nonparametric ,Young Adult ,Risk Factors ,Surgical oncology ,Confidence Intervals ,Humans ,Medicine ,Neurofibroma ,Neoplasm Metastasis ,Neurofibromatosis ,neoplasms ,Prior Radiation Therapy ,Aged ,Proportional Hazards Models ,Retrospective Studies ,Aged, 80 and over ,business.industry ,Soft tissue sarcoma ,Middle Aged ,medicine.disease ,Neoadjuvant Therapy ,eye diseases ,nervous system diseases ,Survival Rate ,Radiation therapy ,Oncology ,Chemotherapy, Adjuvant ,Multivariate Analysis ,Female ,Radiotherapy, Adjuvant ,Surgery ,Neoplasm Recurrence, Local ,business ,Nerve sheath neoplasm ,Follow-Up Studies - Abstract
Malignant peripheral nerve sheath tumors (MPNSTs) occur sporadically, after prior radiation therapy (RT), or in association with neurofibromatosis type 1 (NF1). It is controversial whether patients with NF1-associated MPNST have worse outcomes. We investigated the prognostic significance of sporadic, NF1-associated, and RT-induced MPNST.Patients with primary high-grade MPNST from 1982 to 2011 were identified from a prospectively maintained database. Patients with sporadic MPNST were included only if the MPNST was not associated with NF1 or a neurofibroma or if it was immunohistochemically S100-positive.We studied 105 patients; 42 had NF1-associated tumors, 49 sporadic, and 14 RT-induced. Median age at diagnosis was 38 years. Median follow-up for surviving patients was 4 years. Mean tumor diameter was 5.5 cm for RT-induced tumors and 9.7 cm for NF1-associated and sporadic tumors (P=0.004). In multivariate analysis, factors associated with worse disease-specific survival (DSS) were larger size (HR 1.08; 95% CI 1.04-1.13; P0.001) and positive margin (HR 3.30; 95% CI 1.74-6.28; P0.001). Age, gender, site of disease, and S100 staining were not associated with DSS. The 3-year and median DSS were similar for NF1 and sporadic cases; combined 3-year DSS was 64% and median DSS was 8.0 years. For RT-induced tumors, 3-year DSS was 49% and median DSS was 2.4 years. The relationship between RT association and DSS approached statistical significance (HR 2.29; 95% CI 0.93-5.67; P=0.072).Margin status and size remain the most important predictors of DSS in patients with MPNST. NF1-associated and sporadic MPNSTs may be associated with improved DSS compared with RT-induced tumors.
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- 2012
9. Soft tissue sarcoma diagnosed subsequent to lymphoma is associated with prior radiotherapy and decreased survival
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Keith Baldwin, Anthony Buglino, Samuel Singer, Nicole Moraco, Murray F. Brennan, Giorgos C. Karakousis, and Steven C. Katz
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Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,Soft tissue sarcoma ,medicine.medical_treatment ,Odds ratio ,Disease ,medicine.disease ,Confidence interval ,Surgery ,Lymphoma ,Radiation therapy ,Leukemia ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Sarcoma ,business - Abstract
BACKGROUND: Cancer survivors are at increased risk for second malignancies, and vigilance is thus required. The authors sought to determine whether there was an association among lymphoma, sarcoma, and the associated treatments for these diseases. METHODS: From the authors' prospective soft tissue sarcoma (STS) database of 8240 patients, they identified 112 patients with STS and lymphoma treated from 1982 to 2009 who had complete follow-up data. They examined the importance of the initial diagnosis in patients with both STS and lymphoma, in addition to determining the role of radiation therapy, a known inducer of sarcoma. RESULTS: Review of their sarcoma, gastric, urology, breast, and gynecology databases revealed that lymphoma (95%) or leukemia (5%) occurred in 1.6% of STS patients in comparison to 0.5% of patients in the other databases (P < .01; odds ratio, 3.1; 95% confidence interval, 2.6-3.8). Patients diagnosed with STS only were more likely to die of disease at 10 years compared with those with STS and lymphoma (P = .006), but this difference was not significant when patients presenting with recurrence or metastases were excluded. Among patients with lymphoma and STS, lymphoma was the first diagnosis in 71% of patients. Median survival after STS diagnosis was shorter when lymphoma was the initial diagnosis (67 vs 170 months, P = .002), and these patients were more likely to have radiation-associated STS (44% vs 3%, P < .001). CONCLUSIONS: There was a 3-fold higher incidence of lymphoma in STS patients compared with other solid tumors. The poor prognosis of those diagnosed with both STS and lymphoma was most likely a consequence of prior irradiation. Cancer 2011. © 2011 American Cancer Society.
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- 2011
10. Do Radiation-Associated Soft Tissue Sarcomas Have the Same Prognosis As Sporadic Soft Tissue Sarcomas?
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Li-Xuan Qin, Kaled M. Alektiar, Mark A. Edgar, Nicole Moraco, Murray F. Brennan, Cristina R. Antonescu, Rebecca A. Gladdy, and Samuel Singer
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Adult ,Leiomyosarcoma ,Male ,Cancer Research ,Pathology ,medicine.medical_specialty ,Neoplasms, Radiation-Induced ,Time Factors ,Adolescent ,Fibrosarcoma ,medicine.medical_treatment ,Hemangiosarcoma ,Histiocytoma, Malignant Fibrous ,Kaplan-Meier Estimate ,Risk Assessment ,Nerve Sheath Neoplasms ,Young Adult ,Risk Factors ,Original Reports ,medicine ,Humans ,Aged ,Neoplasm Staging ,Proportional Hazards Models ,Aged, 80 and over ,Radiotherapy ,Proportional hazards model ,business.industry ,Soft tissue sarcoma ,Hazard ratio ,Soft tissue ,Sarcoma ,Middle Aged ,Prognosis ,medicine.disease ,Radiation therapy ,Oncology ,Female ,business ,Nerve sheath neoplasm - Abstract
Purpose To determine the prognostic significance of histologic type in radiation-associated soft tissue sarcomas (RASs) and determine whether RASs are associated with an inferior prognosis compared with sporadic soft tissue sarcomas (STSs). Patients and Methods One hundred thirty primary RASs were identified from 7,649 STS patients from 1982 to 2007. Multivariate analysis of clinicopathologic factors for disease-specific survival (DSS) was performed for RASs, and a multivariate analysis of radiation exposure was also performed for RASs and sporadic sarcomas. A matched-cohort analysis was performed for radiation-associated and sporadic malignant fibrous histiocytoma (MFH). Results Most RASs were high grade (83%), deep (87%), and truncal (61.5%). The median interval between radiation therapy and RAS development was 10 years (range, 1.3 to 74 years), which varied significantly by histologic type (P = .003). The 5-year DSS was 58%, and independent predictors were size > 5 cm, margin positivity, and histologic type. Multivariate analysis of histologic types of primary, high-grade radiation-associated and sporadic STSs showed that RAS was associated with a worse DSS (hazard ratio, 1.7; range, 1.1 to 2.4; P = .007). For pleomorphic MFH—the most common RAS type—the 5-year DSS was 44% versus 66% in a matched cohort of sporadic MFH patients (P = .07). DSS was significantly worse in primary RAS malignant peripheral nerve sheath tumors (MPNSTs) compared with unmatched sporadic MPNSTs (P = .001). Conclusion Histologic type, margin status, and tumor size are the most important independent predictors of DSS in patients with RASs. DSS in patients with primary RAS is significantly worse compared with sporadic STS independent of sarcoma histologic type.
- Published
- 2010
11. Soft tissue sarcoma of the headneck: nomogram validation and analysis of staging systems
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Andrew G, Shuman, Murray F, Brennan, Frank L, Palmer, Deborah, Kuk, Nicole, Moraco, Samuel, Singer, Jatin P, Shah, and Snehal G, Patel
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Male ,Nomograms ,Head and Neck Neoplasms ,Humans ,Female ,Sarcoma ,Middle Aged ,Prognosis ,Disease-Free Survival ,Article ,Neoplasm Staging - Abstract
Soft tissue sarcomas of the head and neck (STSHN) comprise a rare group of malignancies. Our objective is to determine the utility of soft tissue sarcoma staging systems within the head and neck, and to validate an individualized soft tissue sarcoma nomogram within head and neck primary sites.Previously-untreated patients with STSHN diagnosed and treated between 1982 and 2012 were eligible (n = 319, median follow-up 46 months). Clinical variables were extracted from a prospectively-maintained database. The performance of AJCC/UICC and MSK staging systems and a soft tissue sarcoma-specific nomogram were assessed.Four-year overall survival (OS), disease specific survival (DSS), and recurrence-free survival (RFS) were 72%, 76%, and 71%, respectively. AJCC/UICC and MSK staging systems accurately stratified outcomes (OS, DSS, and RFS; P0.001 for all comparisons). The nomogram stratified outcomes by quartile (P0.001), and predicted risk of death at 4, 8 and 12 years (P0.001). Concordance indices for overall survival for the AJCC/UICC system, MSK system, and the nomogram were 0.71, 0.70, and 0.78, respectively.Oncologic outcomes among groups of patients with STSHN can be accurately predicted using both the AJCC/UICC and MSK staging systems. A soft tissue sarcoma-specific nomogram provides reliable, individualized prognostic information for patients with STSHN.
- Published
- 2014
12. Toward better soft tissue sarcoma staging: building on american joint committee on cancer staging systems versions 6 and 7
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Meera Hameed, Murray F. Brennan, Robert G. Maki, Nicole Moraco, Alisa Pinkhasik, Cristina R. Antonescu, and Samuel Singer
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Male ,medicine.medical_specialty ,Primary tumor size ,Article ,medicine ,Humans ,Medical physics ,Prospective Studies ,Cancer staging ,Neoplasm Staging ,business.industry ,Soft tissue sarcoma ,Sarcoma ,Patient data ,Middle Aged ,medicine.disease ,Prognosis ,Combined Modality Therapy ,Surgery ,Survival Rate ,Oncology ,Lymphatic Metastasis ,Female ,Neoplasm Recurrence, Local ,business ,Follow-Up Studies - Abstract
Based on review of patient data in case conferences over time, we hypothesized that clinically relevant data are omitted in routine soft tissue sarcoma staging.We examined subsets of a prospectively collected single institution soft tissue sarcoma database with respect to criteria of the AJCC versions 6 (2002) and 7 (2010) staging systems and examined their clinical outcomes.Relapse-free survival decreases with increasing primary tumor size in four categories, versus two categories used in AJCC 6 and 7 staging. Disease-specific survival decreases over three categories. Conversely, omission of tumor depth as a prognostic factor in version 7 appears supported, since tumor depth is not an independent risk factor for disease-specific survival by multivariate analysis. Patients with nodal disease and no other metastases fare better than patients with other metastases, but have inferior outcomes compared with patients with large high-grade tumors without nodal metastasis. Multivariate analysis identified size, site, grade, age, nodal metastatic disease, and other metastatic disease as independent risk factors for disease-specific survival. Versions 6 and 7 criteria are tacit regarding anatomic site and histology for tumors with identical FNCLCC grade.Improved patient risk assessment may be achieved by staging using a larger number of size categories. Staging system refinements come at the cost of a larger number of staging categories. Histology or site-specific staging systems, nomograms or Bayesian belief networks may provide more accurate means to assess clinical outcomes.
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- 2013
13. Expression Profiling of Liposarcoma Yields a Multigene Predictor of Patient Outcome and Identifies Genes that Contribute to Liposarcomagenesis
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Cristina R. Antonescu, Samuel Singer, Ryan M. Gobble, Rachael O'Connor, Nicole Moraco, Elliott R. Brill, Stacy Ugras, Penelope DeCarolis, Christina V. Angeles, and Li-Xuan Qin
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Primary Liposarcoma ,Adult ,Male ,Cancer Research ,Concordance ,Apoptosis ,Liposarcoma ,Biology ,Bioinformatics ,Article ,Disease-Free Survival ,Cohort Studies ,Antigens, Neoplasm ,Predictive Value of Tests ,Cell Line, Tumor ,medicine ,Humans ,Genetic Predisposition to Disease ,RNA, Small Interfering ,Poly-ADP-Ribose Binding Proteins ,Gene ,Aged ,Oligonucleotide Array Sequence Analysis ,Aged, 80 and over ,Framingham Risk Score ,Soft tissue sarcoma ,Gene Expression Profiling ,Receptor Protein-Tyrosine Kinases ,Middle Aged ,medicine.disease ,Up-Regulation ,Gene expression profiling ,DNA-Binding Proteins ,DNA Topoisomerases, Type II ,Oncology ,Predictive value of tests ,Gene Knockdown Techniques ,Checkpoint Kinase 1 ,Female ,Cell Adhesion Molecules ,Protein Kinases - Abstract
Liposarcomas are the most common type of soft tissue sarcoma but their genetics are poorly defined. To identify genes that contribute to liposarcomagenesis and serve as prognostic candidates, we undertook expression profiling of 140 primary liposarcoma samples, which were randomly split into training set (n = 95) and test set (n = 45). A multigene predictor for distant recurrence-free survival (DRFS) was developed by the supervised principal component method. Expression levels of the 588 genes in the predictor were used to calculate a risk score for each patient. In validation of the predictor in the test set, patients with low risk score had a 3-year DRFS of 83% versus 45% for high risk score patients (P = 0.001). The HR for high versus low score, adjusted for histologic subtype, was 4.42 (95% CI, 1.26–15.55; P = 0.021). The concordance probability for risk score was 0.732. In contrast, the concordance probability for histologic subtype, which had been considered the best predictor of outcome in liposarcoma, was 0.669. Genes related to adipogenesis, DNA replication, mitosis, and spindle assembly checkpoint control were all highly represented in the multigene predictor. Three genes from the predictor, TOP2A, PTK7, and CHEK1, were found to be overexpressed in liposarcoma samples of all five subtypes and in liposarcoma cell lines. RNAi-mediated knockdown of these genes in liposarcoma cell lines reduced proliferation and invasiveness and increased apoptosis. Taken together, our findings identify genes that seem to be involved in liposarcomagenesis and have promise as therapeutic targets, and support the use of this multigene predictor to improve risk stratification for individual patients with liposarcoma. Cancer Res; 71(7); 2697–705. ©2011 AACR.
- Published
- 2011
14. Soft tissue sarcoma diagnosed subsequent to lymphoma is associated with prior radiotherapy and decreased survival
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Steven C, Katz, Keith, Baldwin, Giorgos, Karakousis, Nicole, Moraco, Anthony, Buglino, Samuel, Singer, and Murray F, Brennan
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Adult ,Male ,Lymphoma ,Radiotherapy ,Incidence ,Neoplasms, Second Primary ,Sarcoma ,Kaplan-Meier Estimate ,Middle Aged ,Disease-Free Survival ,Medical Records ,Prevalence ,Humans ,Female ,New York City ,Survivors ,Aged ,Retrospective Studies - Abstract
Cancer survivors are at increased risk for second malignancies, and vigilance is thus required. The authors sought to determine whether there was an association among lymphoma, sarcoma, and the associated treatments for these diseases.From the authors' prospective soft tissue sarcoma (STS) database of 8240 patients, they identified 112 patients with STS and lymphoma treated from 1982 to 2009 who had complete follow-up data. They examined the importance of the initial diagnosis in patients with both STS and lymphoma, in addition to determining the role of radiation therapy, a known inducer of sarcoma.Review of their sarcoma, gastric, urology, breast, and gynecology databases revealed that lymphoma (95%) or leukemia (5%) occurred in 1.6% of STS patients in comparison to 0.5% of patients in the other databases (P.01; odds ratio, 3.1; 95% confidence interval, 2.6-3.8). Patients diagnosed with STS only were more likely to die of disease at 10 years compared with those with STS and lymphoma (P = .006), but this difference was not significant when patients presenting with recurrence or metastases were excluded. Among patients with lymphoma and STS, lymphoma was the first diagnosis in 71% of patients. Median survival after STS diagnosis was shorter when lymphoma was the initial diagnosis (67 vs 170 months, P = .002), and these patients were more likely to have radiation-associated STS (44% vs 3%, P.001).There was a 3-fold higher incidence of lymphoma in STS patients compared with other solid tumors. The poor prognosis of those diagnosed with both STS and lymphoma was most likely a consequence of prior irradiation.
- Published
- 2010
15. Dermatofibrosarcoma protuberans (DFSP): predictors of recurrence and the use of systemic therapy
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Samuel Singer, Ryan C. Fields, Robert G. Maki, Meera Hameed, Li-Xuan Qin, Murray F. Brennan, Nicole Moraco, and Xiaoyu Jia
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Oncology ,Adult ,Male ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Malignancy ,Article ,Young Adult ,Surgical oncology ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Dermatofibrosarcoma protuberans ,medicine ,Humans ,Prospective Studies ,Survival rate ,Aged ,Univariate analysis ,business.industry ,Dermatofibrosarcoma ,Radiotherapy Dosage ,Middle Aged ,medicine.disease ,Combined Modality Therapy ,Surgery ,Radiation therapy ,Survival Rate ,Imatinib mesylate ,Treatment Outcome ,Female ,Sarcoma ,Neoplasm Recurrence, Local ,business ,Follow-Up Studies - Abstract
Dermatofibrosarcoma protuberans (DFSP) is an uncommon soft tissue malignancy that typically presents with local invasion but rarely metastasizes. We examine clinicopathologic factors associated with disease-free survival (DFS) in patients with primary and recurrent DFSP and evaluate responses to multimodality therapy. Patients treated for DFSP were identified in a prospectively maintained database. Clinicopathologic factors associated with DFS were analyzed using univariate and multivariate analysis. A total of 244 patients with DFSP were identified. Median follow-up was 50 months. A total of 14 patients had local recurrence (LR), and 2 patients had distant recurrence (DR), with a median time to recurrence of 35 months. At time of last follow-up, 70% and 47% of patients showed no evidence of disease (NED) in the primary (n = 197) and recurrent groups (n = 47), respectively. On univariate analysis, tumor location and depth were associated with DFS in the primary group, while margin status (R1 vs. R0) was associated with DFS in the LR group. On multivariate analysis, only depth (primary group) and margin status (LR group), remained significant. Also, 22 patients had therapy other than surgical resection: 14 radiotherapy, 4 tyrosine kinase inhibitor (TKI) only, 2 conventional chemotherapy only, and 2 chemotherapy plus TKI. Responses to other therapies were variable. DFS after treatment for DFSP is strongly predicted by tumor depth in the primary setting and margin status in recurrent tumors. The treatment for DFSP in the primary or recurrent setting is excision with negative margins, resulting in low recurrence rates and infrequent metastatic spread. Multimodality treatment, especially TKI use, can be effective, but is not curative.
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- 2010
16. Poor prognostic features in angiosarcoma: A single institution retrospective study of 324 patients
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Sandra P. D'Angelo, Mark A. Dickson, Nicole Moraco, Cristina R. Antonescu, Mrinal M. Gounder, Richard D. Carvajal, Samuel Singer, William D. Tap, Deborah Kuk, Gary K. Schwartz, Li-Xuan Qin, and Mary Louise Keohan
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Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,Retrospective cohort study ,Disease ,Surgery ,Internal medicine ,medicine ,Overall survival ,Malignant Endothelial Cell ,Angiosarcoma ,Single institution ,business - Abstract
10580 Background: Angiosarcoma (AS) is a rare, malignant endothelial cell tumor of vascular origin with a five year overall survival (OS) of approximately 35%. It is a heterogenous disease whose natural history is poorly defined. We sought to identify clinical and treatment outcomes to better define this disease. Methods: In a retrospective study using an institutional sarcoma database, we identified all patients(pts) with AS treated at Memorial Sloan-Kettering Cancer Center between 1992-2011 and collected their correlative clinical information.Kaplan-Meier method and Cox’s proportional-hazard models were used to determine OS and prognostic factors. Hazard ratios (HR) are listed with their 95%confidence intervals (CI). Results: We identified 324 pts, median age was 63 (range 15-94), 127(39%) were men. At presentation, 188 (58%), 19 (6%) and 117(36%) had localized disease (L), local recurrences (LR) or distant metastases (M), respectively. L sites included: RT breast 43 (23%,) head&neck 33 (18%,) scalp 30 (16%,) breast 26 (14%,) extremity 23 (12%,) abdomen/pelvis 14 (7%,) thorax 10 (5%) and trunk 9 (5%). The median OS is 3.3 years (2.44-4.33) for pts w L disease and 0.89 years (0.74-1.11) for pts with M disease. Among pts that presented with L disease, 29% had a LR and the median local relapse free survival (RFS) time was not reached (8.71-NA); 31% had distant recurrences with a median distant RFS of 12.8 yrs (4.13-NA.) Among L disease patients, older age (HR 1.04, 1.03-1.06, p
- Published
- 2013
17. How well do we communicate risk? An evaluation of AJCC version 6 and 7 staging systems for soft tissue sarcomas
- Author
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Nicole Moraco, Cristina R. Antonescu, Meera Hameed, Murray F. Brennan, Samuel Singer, and Robert G. Maki
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Cancer Research ,medicine.medical_specialty ,Oncology ,business.industry ,medicine ,Soft tissue ,Medical physics ,business ,Surgery ,Cancer staging - Abstract
10001 Background: Cancer staging systems allow physicians to communicate risks of a particular clinical situation with one another and with patients. Few data have been presented to support the update of a commonly employed staging system for soft tissue sarcoma (STS). We examined American Joint Committee on Cancer (AJCC) versions 6 (2002) and 7 (2010) staging systems for patients with primary STS using a single institution clinically annotated prospective database. Methods: Subsets of the prospectively collected Memorial Sloan-Kettering Cancer Center STS database of 8647 patients from 1982 to 2010 were examined with respect to criteria of the AJCC versions 6 and 7 staging systems. Results: Tumor size does not appear to be adequately addressed in version 6 or 7. Relapse-free survival was statistically worse for increasing size of primary STS 15 cm; in comparison, overall survival decreased over three size categories (10 cm). Tumor depth, a statistically significant factor in patient outcomes that is included in version 6, is functionally omitted in version 7. Patients with node involvement without other metastases fare statistically worse than patients with large, high grade tumors without nodal metastasis, as shown previously. Version 6 and 7 criteria do not address effects of primary anatomic site and histology, even for tumors with same FNCLCC grade. Sarcoma subtypes defined after publication of FNCLCC criteria are difficult to incorporate into existing guidelines. Conclusions: Improved prognostication of STS outcomes is better achieved by staging according to anatomic primary site, depth, and a larger number of size categories. Histology-specific nomograms improve prognostic accuracy, such as those for liposarcoma, GIST, or rhabdomyosarcoma. Staging accuracy increases at the cost of portability and simplicity. The increasing difficulties with use of a single STS staging system highlight the potential benefit of newer techniques, such as patient-specific nomograms or Bayesian networks. Staging systems will require significant modifications to incorporate increasingly sophisticated molecular diagnostics.
- Published
- 2012
18. Activity of sorafenib in radiation-associated breast angiosarcomas harboring MYC and FLT4 amplifications
- Author
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Nicole Moraco, Cristina R. Antonescu, Mrinal M. Gounder, Mary Louise Keohan, Mark A. Dickson, Richard D. Carvajal, Sandra P. D'Angelo, Samuel Singer, Gary K. Schwartz, and William D. Tap
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Sorafenib ,Cancer Research ,education.field_of_study ,business.industry ,Angiogenesis ,medicine.medical_treatment ,Population ,Cancer ,medicine.disease ,Endothelial cell differentiation ,FLT4 ,Radiation therapy ,Oncology ,Cancer research ,Medicine ,Sarcoma ,business ,education ,medicine.drug - Abstract
10019 Background: Angiosarcomas (ASs) are rare, aggressive vascular malignancies of endothelial cell differentiation which arise de novo or secondary to radiation therapy (RAS.) A subset of patients(pts) with AS harbor mutations in KDR (VEGFR-2) or overexpression of MYC and/or FLT4(VEGFR-3). MYC & FLT4 gene amplifications occur almost exclusively in RAS. These alterations provide a rationale for investigating agents that target angiogenesis in RAS. In a phase II trial of sorafenib, AS pts had a partial response (PR) of 14%; targeting the appropriate pt population may be essential. We hypothesize that co-amplification of MYC & FLT4 may be predictive of response to sorafenib. Methods: Using our institutional sarcoma database & data query system, we identified AS patients treated with sorafenib at Memorial Sloan-Kettering Cancer Center between 1992-2011. Molecular analysis performed on available tissue. With IRB approval, clinical information was collected. Results: We identified 10 women with RAS that received sorafenib. Average age 68 (range 51-84.) 7 pts had distant metastatic disease. Median lines of systemic therapy prior to sorafenib: 2 (range 1-4.) Sorafenib was first line in 60% of pts, administered at 400mg daily and adjusted for toxicity. Best responses included: complete response (CR) 2/9(22%), PR 1/9(11%), stable disease (SD) 5/9(56%) range 5-23m, progressive disease 1/9(11%) for a clinical benefit rate of (CR+PR+SD) 89%. Responses were seen in patients with lung metastases (n=2) and locally advanced disease (n=1) and were durable for 17, 42 and 26 months. Median duration on therapy was 15 months (range 0-42 months.) 7 pts underwent molecular analysis: co-amplification of MYC & FLT4 3 pts (30%); MYC amplification 4 pts (40%); KDR mutation 0 patients. Of the 3 responders, MYC & FLT4 co-amplification were observed in 2 patients and not evaluated in one. Conclusions: Sorafenib is active against RAS of the breast. In this small series, complete and partial responses were seen in patients with co-amplification of MYC & FLT4. This observation requires further study. Performing molecular studies on all AS pts will help define the pathophysiology of this deadly disease to guide rationale clinical trials.
- Published
- 2012
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