A web-based prognostic tool for extremity and trunk wall soft tissue sarcomas and its external validation.
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ABSTRACT:
SUBMITTER: Sampo M
PROVIDER: S-EPMC3304417 | biostudies-other | 2012 Mar
REPOSITORIES: biostudies-other
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Project description:BackgroundPrognostic nomograms for patients with extremity soft tissue sarcoma (eSTS) typically predict survival or the occurrence of local recurrence or distant metastasis at time of surgery. Our aim was to develop and externally validate a dynamic prognostic nomogram for overall survival in eSTS survivors for use during follow-up.MethodsAll primary eSTS patients operated with curative intent between 1994 and 2013 at three European and one Canadian sarcoma centers formed the development cohort. Patients with Fédération Française des Centres de Lutte Contre le Cancer (FNCLCC) grade II and grade III eSTS operated between 2000 and 2016 at seven other European reference centers formed the external validation cohort. We used a landmark analysis approach and a multivariable Cox model to create a dynamic nomogram; the prediction window was fixed at five years. A backward procedure based on the Akaike Information Criterion was adopted for variable selection. We tested the nomogram performance in terms of calibration and discrimination.FindingsThe development and validation cohorts included 3740 and 893 patients, respectively. The variables selected applying the backward procedure were patient's age, tumor size and its interaction with landmark time, tumor FNCLCC grade and its interaction with landmark time, histology, and both local recurrence and distant metastasis (as first event) indicator variables. The nomogram showed good calibration and discrimination. Harrell C indexes at different landmark times were between 0.776 (0.761-0.790) and 0.845 (0.823-0.862) in the development series and between 0.675 (0.643-0.704) and 0.810 (0.775-0.844) in the validation series.InterpretationA new dynamic nomogram is available to predict 5-year overall survival at different times during the first three years of follow-up in patients operated for primary eSTS. This nomogram allows physicians to update the individual survival prediction during follow-up on the basis of baseline variables, time elapsed from surgery and first-event history.
| S-EPMC6933187 | biostudies-literature
Project description:Soft tissue sarcoma (STS) of the extremities is typically treated with limb-sparing surgery and radiation therapy; with this treatment approach, high local control rates can be achieved. However, postradiation bone fractures, fractures occurring in the prior radiation field with minimal or no trauma, are a serious late complication that occurs in 2-22% of patients who receive surgery and radiation for STS. Multiple risk factors for sustaining a postradiation fracture exist, including high radiation dose, female sex, periosteal stripping, older age, femur location, and chemotherapy administration. The treatment of these pathological fractures can be difficult, with complications including delayed union, nonunion, and infection posing particular challenges. Here, we review the mechanisms, risk factors, and treatment challenges associated with postradiation fractures in STS patients.
| S-EPMC7984930 | biostudies-literature
Project description:BACKGROUND:The use of nomograms for prognostication of individual cancer patients has been recommended in order to facilitate precision medicine. However, models for patients with soft tissue sarcomas (STSs) are limited because of the rarity and heterogeneity of such cancers. In addition, no model has been developed on the basis of an Asian cohort. Here, we attempted to develop and internally validate nomograms for patients with localized STSs of the trunk and extremity. METHODS:This study retrospectively extracted 2827 patients with primary trunk and extremity STSs after definitive surgery using the Bone and Soft Tissue Tumor Registry, which is a nationwide sarcoma database in Japan. We developed three nomograms predicting the probability of local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS) and disease-specific survival (DSS) at 2 years after surgery, using the Cox multivariate model. The nomograms were internally validated for discrimination and calibration using bootstrap resampling and assessed for their clinical applicability by decision curve analysis (DCA). RESULTS:Local recurrence, distant metastasis and disease-specific death occurred in 241 patients (8.5%), 554 patients (19.6%) and 230 patients (8.1%), respectively. Histological diagnosis, grade and tumor size strongly influenced all three endpoints. The nomograms predicted accurately the probability of LRFS, DMFS and DSS (concordance index: 0.73, 0.70 and 0.75, respectively). DCA demonstrated that our nomograms had clinical applicability. CONCLUSION:We have developed the first nomograms for STSs based on an Asian cohort. These nomograms allowed accurate prediction of LRFS, DMFS and DSS at 2 years after definitive surgery, and can be used as a guide by clinicians for appropriate follow-up and counseling of patients.
| S-EPMC6610844 | biostudies-other
Project description:BackgroundThe rapid spread of coronavirus disease 2019 (COVID-19) revealed significant constraints in critical care capacity. In anticipation of subsequent waves, reliable prediction of disease severity is essential for critical care capacity management and may enable earlier targeted interventions to improve patient outcomes. The purpose of this study is to develop and externally validate a prognostic model/clinical tool for predicting COVID-19 critical disease at presentation to medical care.MethodsThis is a retrospective study of a prognostic model for the prediction of COVID-19 critical disease where critical disease was defined as ICU admission, ventilation, and/or death. The derivation cohort was used to develop a multivariable logistic regression model. Covariates included patient comorbidities, presenting vital signs, and laboratory values. Model performance was assessed on the validation cohort by concordance statistics. The model was developed with consecutive patients with COVID-19 who presented to University of California Irvine Medical Center in Orange County, California. External validation was performed with a random sample of patients with COVID-19 at Emory Healthcare in Atlanta, Georgia.ResultsOf a total 3208 patients tested in the derivation cohort, 9% (299/3028) were positive for COVID-19. Clinical data including past medical history and presenting laboratory values were available for 29% (87/299) of patients (median age, 48 years [range, 21-88 years]; 64% [36/55] male). The most common comorbidities included obesity (37%, 31/87), hypertension (37%, 32/87), and diabetes (24%, 24/87). Critical disease was present in 24% (21/87). After backward stepwise selection, the following factors were associated with greatest increased risk of critical disease: number of comorbidities, body mass index, respiratory rate, white blood cell count, % lymphocytes, serum creatinine, lactate dehydrogenase, high sensitivity troponin I, ferritin, procalcitonin, and C-reactive protein. Of a total of 40 patients in the validation cohort (median age, 60 years [range, 27-88 years]; 55% [22/40] male), critical disease was present in 65% (26/40). Model discrimination in the validation cohort was high (concordance statistic: 0.94, 95% confidence interval 0.87-1.01). A web-based tool was developed to enable clinicians to input patient data and view likelihood of critical disease.Conclusions and relevanceWe present a model which accurately predicted COVID-19 critical disease risk using comorbidities and presenting vital signs and laboratory values, on derivation and validation cohorts from two different institutions. If further validated on additional cohorts of patients, this model/clinical tool may provide useful prognostication of critical care needs.
| S-EPMC7725393 | biostudies-literature
Project description:Background Recent studies have suggested that the quantity and quality of adipose tissue and muscle, assessed on non-contrast computed tomography (CT), may serve as imaging biomarkers of survival in patients with and without neoplasms. Purpose To assess body composition measures that could serve as predictors of therapy response in patients with extremity soft tissue sarcomas treated with radiation therapy and surgery. Material and Methods The study was IRB-approved. Sixty patients had a history of extremity soft tissue sarcoma and underwent FDG-PET/CT prior to radiation therapy and surgical resection. Cross-sectional areas and CT attenuation (HU) of abdominal subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and psoas muscle were assessed on non-contrast CT. Clinical information on predictors of tumor recurrence and post-surgical wound infections were recorded. Cox proportional hazard models were used to determine longitudinal associations between body composition and tumor recurrence/wound infections. Results Twenty-three tumor recurrences occurred over a follow-up period of 43?±?35 months. Higher SAT and lower psoas attenuation were associated with tumor recurrence which remained significant after adjustment for covariates ( P???0.01). There were 13 post-surgical wound infections. Higher VAT and SAT attenuation were associated with post-surgical wound infections ( P?<?0.04); however, VAT attenuation lost significance after adjustment for covariates. Conclusion Abdominal adipose tissue and psoas muscle attenuation assessed on non-contrast CT may predict tumor recurrence and post-surgical infections in patients with extremity soft tissue sarcomas.
| S-EPMC6063528 | biostudies-literature
Project description:The use of upfront chemotherapy for primary localized soft tissue sarcoma (STS) of the extremity and trunk is debated. It remains unclear if chemotherapy adds clinical benefit, which patients are likely to benefit, and whether the timing of therapy affects outcomes. We used the National Cancer Database (NCDB) to examine the association between overall survival (OS) and chemotherapy in 5436 patients with the five most common subtypes of STS with primary disease localized to the extremity or trunk, mirroring the patient population of a modern phase 3 clinical trial of neoadjuvant chemotherapy. We then examined associations between timing of multi-agent chemotherapy (neoadjuvant or adjuvant) and OS. We used a Cox proportional hazards model and propensity score matching (PSM) to account for covariates including demographic, patient, clinical, treatment, and facility factors. In the overall cohort, we observed no association between multi-agent chemotherapy or its timing and improved OS. Multi-agent chemotherapy was associated with improved OS in several subgroups, including patients with larger tumors (>5 cm), those treated at high-volume centers, or those who received radiation. We also identified an OS benefit to multi-agent chemotherapy among the elderly (>70 years) and African American patients. Multi-agent chemotherapy was associated with improved survival for patients with tumors >5 cm, who receive radiation, or who receive care at high-volume centers. Neither younger age nor chemotherapy timing was associated with better outcomes. These 'real-world' findings align with recent randomized trial data supporting the use of multi-agent chemotherapy in high-risk patients with localized STS.
| S-EPMC7564235 | biostudies-literature
Project description:ObjectiveRecent studies have investigated the significance of GATA3 expression in patients with various malignant tumors. However, no previous studies have evaluated the clinicopathological importance of GATA3 expression in soft tissue sarcomas (STS) patients.MethodsWe evaluated GATA3 expression in 76 STS cases using immunohistochemical analysis, and statistically compared clinicopathological characteristics between GATA3-positive and GATA3-negative cases.ResultGATA3-positive expression was significantly associated with a higher mitotic count (P < 0.0001). Disease-free survival (DFS) of GATA3-positive cases was significantly shorter than that of cases without GATA3 expression (P = 0.0104). Overall survival (OS) of GATA3-positive cases was significantly shorter than that of cases without GATA3 expression (P = 0.0006). GATA3-positive expression was significantly associated with shorter DFS in both univariate analysis (hazard ratio [HR], 2.719; P = 0.012) and multivariate analysis (HR, 2.711; P = 0.014). GATA3-positive expression was also significantly associated with worse OS in both univariate analysis (HR, 5.730; P = 0.0007) and multivariate analysis (HR, 5.789; P = 0.0008).ConclusionThese results indicate that GATA3 is an independent prognostic factor and suggest that evaluation of GATA3 expression might enable more effective clinical follow-up using prognostic stratification of STS patients.
| S-EPMC4889143 | biostudies-literature
Project description:Background Although clinicians and patients with extremity bone and soft tissue (EBST) are increasingly interested in limb salvage surgery (LSS), because of the minimal damage to physical appearance and function, however, there is still a lack of large-scale population studies on whether LSS improves the prognosis of patients. Purpose The aim of this study was to compare the survival of patients with EBST sarcomas after receiving LSS and amputation. Methods To conduct the population-based study, we identified 6,717 patients with a histologically diagnosed bone sarcoma and 24,378 patients with a histologically diagnosed soft tissue sarcoma from the Surveillance, Epidemiology, and End Results database. We analyzed overall survival (OS), cancer-specific survival (CSS), and non-sarcoma survival (NSS) using the Kaplan–Meier method, log-rank test or Gray test, Cox regression model, propensity score-matched analysis, and landmark analysis. Results LSS could improve the prognosis in patients with most EBST subtypes, except for Ewing sarcomas and MPNST. However, in the subgroup without distant metastases, limb salvage increased CSS only for patients with osteosarcoma, Ewing sarcoma, and leiomyosarcoma, as well as NSS for patients with chondrosarcoma and synovial sarcoma. Landmark analysis further demonstrated that sarcoma survivors surviving <10 years could benefit from LSS but not for long-term survivors ≥10 years. Moreover, for patients with distant metastases, LSS could improve survival of osteosarcoma patients but worsen CSS among patients with MPNST. Landmark analysis further demonstrated that LSS improved survival among osteosarcomas patients with distant metastases only within 1 year after surgery. Moreover, patients receiving LSS and those receiving amputation had a high risk of dying from different non-sarcoma diseases during the postoperative follow-up. Conclusions The impact of limb salvage on the prognosis of patients depends on the pathological subtype and stage of EBST sarcomas.
| S-EPMC9208618 | biostudies-literature
Project description:AimTo prospectively assess toxicities of curative-intent intensity-modulated conformal radiotherapy (IMRT) in patients with extremity soft tissue sarcomas (ESTS).MethodsData from 59 consecutive patients with ESTS between 2014 and 2019 were both retrospectively and prospectively analysed. Toxicity data were collected both by confidential mailed survey (39% completed) and medical charts, and graded according to CTCAE v5.0. Normal tissues dosimetric data (healthy soft tissue segment, joint and bone) were included. The healthy soft tissue segment was created by adding 5 cm on either side of the PTV on CT axial slices, the PTV and bone (and articulation if present) were then removed from the generated volume.ResultsIMRT was delivered post-operatively for nearly half of patients (n = 24, 41%), preoperatively for 18 (31%) and exclusively for 17 (28%; salvage: 13% or immediately inoperable: 15%). The median total dose delivered to the planned target volume (PTV) was 50.4 Gy (36-68 Gy) and 13 patients (22%) received a boost. With a median follow-up of 27 months (6-94 months), a total of 87 late effects were identified in 44/59 (75%) patients: 89% G1-2, and 11% G3-4. The main G1-2 toxicities were: functional limitation (36%), oedema (29%), gait disorders (20%), neurological disorders (20%) and chronic pain (32%). G3-4 toxicities were pain (n = 2), arterial stricture (n = 1) and a chronic wound requiring skin graft (n = 2). No bone fracture was observed. Quality of life was rated as good or very good in 70% patients who completed the survey. Larger (>3500 cm3) healthy soft tissue segment volume was associated with decreased late toxicities (p = 0.02). No other predictive factor of toxicity was identified. The 2-year rates of local control, overall survival and recurrence-free survival were 90%, 90% and 64%, respectively.ConclusionHealthy soft tissue segment volume influenced toxicity. Long-term prospective monitoring in a homogeneous population remains critical to assess the impact of IMRT induced chronic toxicity in ESTS patients. This should ideally lead to a validated normal tissue dose constraint (e.g.: healthy soft tissue segment volume > 3500 cm3) to recommend for practitioners to help reduce the late toxicity risk.
| S-EPMC8213831 | biostudies-literature
Project description:Soft tissue sarcomas (STS) are rare, complex tumors with a poor prognosis. The identification of new prognostic biomarkers is needed to improve patient management. Our aim was to determine the methylation status of the 118 CpG sites in the PLAGL1 tumor-suppressor gene P1 CpG island promoter and study the potential prognostic impact of PLAGL1 promoter methylation CpG sites in STS. Training cohorts constituted of 28 undifferentiated sarcomas (US) and 35 leiomyosarcomas (LMS) were studied. PLAGL1 mRNA expression was investigated by microarray analysis and validated by RT-qPCR. Pyrosequencing was used to analyze quantitative methylation of the PLAGL1 promoter. Associations between global promoter or specific CpG site methylation and mRNA expression were evaluated using Pearson's product moment correlation coefficient. Cox univariate and multivariate proportional hazard models were used to assess the predictive power of CpG site methylation status. Sixteen CpG sites associated with PLAGL1 mRNA expression were identified in US and 6 in LMS. Statistical analyses revealed an association between CpG107 methylation status and both overall and metastasis-free survival in US, which was confirmed in a validation cohort of 37 US. The exhaustive study of P1 PLAGL1 promoter methylation identified a specific CpG site methylation correlated with mRNA expression, which was predictive for both metastasis-free and overall survival and may constitute the first US-specific biomarker. Such a biomarker may be relevant for identifying patients likely to derive greater benefit from treatment.
| S-EPMC3829972 | biostudies-literature