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1.
JAMA Netw Open ; 5(3): e221744, 2022 03 01.
Article in English | MEDLINE | ID: mdl-35289860

ABSTRACT

Importance: Crisis standards of care (CSOC) scores designed to allocate scarce resources during the COVID-19 pandemic could exacerbate racial disparities in health care. Objective: To analyze the association of a CSOC scoring system with resource prioritization and estimated excess mortality by race, ethnicity, and residence in a socially vulnerable area. Design, Setting, and Participants: This retrospective cohort analysis included adult patients in the intensive care unit during a regional COVID-19 surge from April 13 to May 22, 2020, at 6 hospitals in a health care network in greater Boston, Massachusetts. Participants were scored by acute severity of illness using the Sequential Organ Failure Assessment score and chronic severity of illness using comorbidity and life expectancy scores, and only participants with complete scores were included. The score was ordinal, with cutoff points suggested by the Massachusetts guidelines. Exposures: Race, ethnicity, Social Vulnerability Index. Main Outcomes and Measures: The primary outcome was proportion of patients in the lowest priority score category stratified by self-reported race. Secondary outcomes were discrimination and calibration of the score overall and by race, ethnicity, and neighborhood Social Vulnerability Index. Projected excess deaths were modeled by race, using the priority scoring system and a random lottery. Results: Of 608 patients in the intensive care unit during the study period, 498 had complete data and were included in the analysis; this population had a median (IQR) age of 67 (56-75) years, 191 (38.4%) female participants, 79 (15.9%) Black participants, and 225 patients (45.7%) with COVID-19. The area under the receiver operating characteristic curve for the priority score was 0.79 and was similar across racial groups. Black patients were more likely than others to be in the lowest priority group (12 [15.2%] vs 34 [8.1%]; P = .046). In an exploratory simulation model using the score for ventilator allocation, with only those in the highest priority group receiving ventilators, there were 43.9% excess deaths among Black patients (18 of 41 patients) and 28.6% (58 of 203 patients among all others (P = .05); when the highest and intermediate priority groups received ventilators, there were 4.9% (2 of 41 patients) excess deaths among Black patients and 3.0% (6 of 203) among all others (P = .53). A random lottery resulted in more excess deaths than the score. Conclusions and Relevance: In this study, a CSOC priority score resulted in lower prioritization of Black patients to receive scarce resources. A model using a random lottery resulted in more estimated excess deaths overall without improving equity by race. CSOC policies must be evaluated for their potential association with racial disparities in health care.


Subject(s)
COVID-19/mortality , Ethnicity/statistics & numerical data , Health Care Rationing/statistics & numerical data , Racial Groups/statistics & numerical data , Residence Characteristics/statistics & numerical data , Standard of Care , Aged , Boston , COVID-19/diagnosis , COVID-19/therapy , Critical Care , Female , Health Priorities , Healthcare Disparities , Hospitalization , Humans , Male , Middle Aged , Organ Dysfunction Scores , Retrospective Studies , Severity of Illness Index , Vulnerable Populations/statistics & numerical data
2.
Ann Thorac Surg ; 96(4): 1223-1228, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23891404

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.


Subject(s)
Neoplasm Recurrence, Local/epidemiology , Sarcoma/epidemiology , Sarcoma/surgery , Thoracic Wall , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Retrospective Studies , Young Adult
3.
Ann Surg Oncol ; 20(1): 66-72, 2013 Jan.
Article in English | MEDLINE | ID: mdl-22878618

ABSTRACT

BACKGROUND: 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. METHODS: 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. RESULTS: 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; P<0.001) and positive margin (HR 3.30; 95% CI 1.74-6.28; P<0.001). 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). CONCLUSIONS: 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.


Subject(s)
Neoplasms, Radiation-Induced/pathology , Neoplasms, Radiation-Induced/therapy , Nerve Sheath Neoplasms/pathology , Nerve Sheath Neoplasms/therapy , Neurofibromatosis 1/pathology , Neurofibromatosis 1/therapy , Adolescent , Adult , Aged , Aged, 80 and over , Chemotherapy, Adjuvant , Confidence Intervals , Female , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Multivariate Analysis , Neoadjuvant Therapy , Neoplasm Metastasis , Neoplasm Recurrence, Local/etiology , Neoplasm, Residual , Proportional Hazards Models , Radiotherapy, Adjuvant , Retrospective Studies , Risk Factors , Statistics, Nonparametric , Survival Rate , Young Adult
4.
Cancer Res ; 71(7): 2697-705, 2011 Apr 01.
Article in English | MEDLINE | ID: mdl-21335544

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.


Subject(s)
Liposarcoma/genetics , Liposarcoma/pathology , Adult , Aged , Aged, 80 and over , Antigens, Neoplasm/biosynthesis , Antigens, Neoplasm/genetics , Apoptosis/genetics , Cell Adhesion Molecules/biosynthesis , Cell Adhesion Molecules/genetics , Cell Line, Tumor , Checkpoint Kinase 1 , Cohort Studies , DNA Topoisomerases, Type II/biosynthesis , DNA Topoisomerases, Type II/genetics , DNA-Binding Proteins/biosynthesis , DNA-Binding Proteins/genetics , Disease-Free Survival , Female , Gene Expression Profiling , Gene Knockdown Techniques , Genetic Predisposition to Disease , Humans , Liposarcoma/metabolism , Male , Middle Aged , Oligonucleotide Array Sequence Analysis , Poly-ADP-Ribose Binding Proteins , Predictive Value of Tests , Protein Kinases/biosynthesis , Protein Kinases/genetics , RNA, Small Interfering/administration & dosage , RNA, Small Interfering/genetics , Receptor Protein-Tyrosine Kinases/biosynthesis , Receptor Protein-Tyrosine Kinases/genetics , Up-Regulation
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