Evaluation of local control in patients with non-metastatic Ewing sarcoma of the bone: A report from the Children's Oncology Group

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 10013-10013
Author(s):  
S. G. DuBois ◽  
M. D. Krailo ◽  
E. F. Cook ◽  
N. J. Tarbell ◽  
C. J. Fryer ◽  
...  
Keyword(s):  
Disease Progression ◽  
Local Control ◽  
Ewing Sarcoma ◽  
Tumor Size ◽  
Cumulative Incidence ◽  
Hazard Ratio ◽  
Local Failure ◽  
Control Mode ◽  
Distant Failure ◽  
Risk Of Disease

10013 Background: Options for local control in patients (pts) with Ewing sarcoma (EWS) include surgery (S), radiation (R), or surgery plus radiation (S+R). The choice of local control depends on factors that also impact outcome in EWS, including tumor site, tumor size, and age. Our objective was to determine if risk of disease progression differs between local control methods, after controlling for potential confounders. Methods: We analyzed the cohort of pts with non-metastatic EWS of the bone treated on Intergroup Study-0091 (Grier et al, NEJM, 2003). Local control decisions were made on an individual basis. We excluded pts with tumors of the skull/face, progression prior to end of local control, or incomplete local control data. Disease progression was recorded from end of local control. Cumulative incidence of disease progression was determined using a competing risks approach. We constructed a Cox proportional hazards model of progression free survival incorporating local control mode and potential confounders into the model. Secondary analyses evaluated overall survival, local failure, and distant failure. Results: 329 pts met eligibility criteria for analysis. 122 pts received S, 142 received R, and 65 received S+R. The cumulative incidence of disease progression at 5 years was 22.1% (95% CI 15.1–29.9%) for S, 36.9% (29.0–44.9%) for R, and 48.1% (35.5- 59.7%) for S+R. Using R as the reference group and controlling for age, tumor size, tumor location, and chemotherapy regimen, the hazard ratio for progression was 0.66 (95% CI 0.38–1.13) for S and 1.55 (0.96–2.49) for S+R. The hazard ratio for death was 0.77 (95% CI 0.44–1.34) for S and 1.46 (0.88–2.42) for S+R. The hazard ratio for local failure was 0.38 (95% CI 0.15–0.98; p=0.04) for S and 0.77 (0.34–1.75) for S+R. The hazard ratio for distant failure was 0.78 (0.42–1.46) for S and 1.60 (0.91–2.82) for S+R. Conclusions: Observed differences in outcome between local control groups are largely due to confounding factors that affect outcome and local control choice. Risk of disease progression, distant failure, or death does not differ between pts who receive S or R. Pts who receive S have a decreased risk of local failure compared to pts who receive R. No significant financial relationships to disclose.

Local Control in Pelvic Ewing Sarcoma: Analysis From INT-0091—A Report From the Children's Oncology Group

2006 ◽  
Vol 24 (24) ◽  
pp. 3838-3843 ◽  
Author(s):  
Torunn I. Yock ◽  
Mark Krailo ◽  
Christopher J. Fryer ◽  
Sarah S. Donaldson ◽  
James S. Miser ◽  
...  
Keyword(s):  
Local Control ◽  
Ewing Sarcoma ◽  
Local Failure ◽  
Distant Failure ◽  
Pelvic Tumors ◽  
Significant Difference ◽  
Study Population ◽  
The Impact ◽  
To Receive

Purpose The impact of the modality used for local control of Ewing sarcoma is uncertain. We investigated the relationship between the type of local control modality, surgery, radiation (RT) or both (S + RT), and subsequent risk for local failure (LF) in patients with nonmetastatic pelvic Ewing sarcoma treated on INT-0091. Patients and Methods Patients ≤ 30 years with Ewing sarcoma, primitive neuroectodermal tumor or primitive sarcoma of bone were randomly assigned to receive chemotherapy with doxorubicin, vincristine, cyclophosphamide, and dactinomycin, (VACA) or with these four drugs alternating with ifosfamide and etoposide (VACA-IE). The local control modality, surgery, RT or both was chosen by the treating physicians. The effect of local control modality was assessed after adjusting for the size of tumor (< 8 cm, ≥ 8 cm) and chemotherapy type. Results Seventy-five patients with pelvic tumors and a median follow-up of 4.4 years (0.6 to 11.4 years) comprised the study population. Twelve underwent surgery, 44 received RT, and 19 received both. The 5-year event-free survival (EFS) and cumulative incidence of LF was 49% and 21% (16%, LF only; 5%, LF and distant failure). There was no significant difference in EFS or LF by tumor size (< 8 cm, ≥ 8 cm), local control (LC) modality, or chemotherapy. However, VACA-IE seems to confer an LC benefit (11% v 30%; P = .06). Conclusion There was no significant effect of local control modality (surgery, RT or S + RT) selected by the treating physicians on rates of local failure or EFS. However, VACA-IE improves LC (11%) compared with previously published results for pelvic Ewing sarcoma.

scholarly journals The Clinical Relevance of p16 and p53 Status in Patients with Squamous Cell Carcinoma of the Vulva

2020 ◽  
Vol 2020 ◽  
pp. 1-8 ◽  
Author(s):  
Ellen L. Barlow ◽  
Neil Lambie ◽  
Mark W. Donoghoe ◽  
Zin Naing ◽  
Neville F. Hacker
Keyword(s):  
Disease Progression ◽  
Tumor Size ◽  
Clinical Relevance ◽  
Multivariable Analysis ◽  
Nodal Metastases ◽  
Hpv Dna ◽  
Hpv Status ◽  
Risk Of Disease ◽  
P53 Status ◽  
P16 Expression

Objective. To investigate the prognostic significance of HPV status in vulvar squamous cell carcinomas (VSCC) and to determine whether preoperative determination of p16 or p53 status would have clinical relevance. Methods. Patients treated for VSCC at a tertiary hospital in Sydney, Australia, from 2002 to 2014, were retrospectively evaluated (n = 119). Histological specimens were stained for p53 and p16 expression, and HPV status was determined by PCR detection of HPV DNA. Results. HPV DNA was detected in 19%, p16 expression in 53%, and p53 expression in 37% of patients. Kaplan–Meier survival estimates indicated that p16/HPV-positive patients had superior five-year disease-free survival (76% versus 42%, resp., p=0.004) and disease-specific survival (DSS) (89% versus 75% resp., p=0.05) than p53-positive patients. In univariate analysis, nodal metastases (p<0.001), tumor size >4 cm (p=0.03), and perineural invasion (p=0.05) were associated with an increased risk of disease progression and p16 expression with a decreased risk (p=0.03). In multivariable analysis, only nodal metastases remained independent for risk of disease progression (p=0.01). For DSS, lymph node metastases (p<0.001) and tumor size (p=0.008) remained independently prognostic. Conclusion. The p16/HPV and p53 status of VSCC allows separation of patients into two distinct clinicopathological groups, although 10% of patients fall into a third group which is HPV, p16, and p53 negative. p16 status was not independently prognostic in multivariable analysis. Treatment decisions should continue to be based on clinical indicators rather than p16 or p53 status.

scholarly journals The effect of targeted agents on outcomes in patients with brain metastases from renal cell carcinoma treated with Gamma Knife surgery

2012 ◽  
Vol 116 (5) ◽  
pp. 978-983 ◽  
Author(s):  
D. Clay Cochran ◽  
Michael D. Chan ◽  
Mebea Aklilu ◽  
James F. Lovato ◽  
Natalie K. Alphonse ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Brain Metastases ◽  
Cell Carcinoma ◽  
Gamma Knife ◽  
Local Control ◽  
Renal Cell ◽  
Local Failure ◽  
Targeted Agents ◽  
Distant Failure

Object Gamma Knife surgery (GKS) has been reported as an effective modality for treating brain metastases from renal cell carcinoma (RCC). The authors aimed to determine if targeted agents such as tyrosine kinase inhibitors, mammalian target of rapamycin inhibitors, and bevacizumab affect the patterns of failure of RCC after GKS. Methods Between 1999 and 2010, 61 patients with brain metastases from RCC were treated with GKS. A median dose of 20 Gy (range 13–24 Gy) was prescribed to the margin of each metastasis. Kaplan-Meier analysis was used to determine local control, distant failure, and overall survival rates. Cox proportional hazard regression was performed to determine the association between disease-related factors and survival. Results Overall survival at 1, 2, and 3 years was 38%, 17%, and 9%, respectively. Freedom from local failure at 1, 2, and 3 years was 74%, 61%, and 40%, respectively. The distant failure rate at 1, 2, and 3 years was 51%, 79%, and 89%, respectively. Twenty-seven percent of patients died of neurological disease. The median survival for patients receiving targeted agents (n = 24) was 16.6 months compared with 7.2 months (n = 37) for those not receiving targeted therapy (p = 0.04). Freedom from local failure at 1 year was 93% versus 60% for patients receiving and those not receiving targeted agents, respectively (p = 0.01). Multivariate analysis showed that the use of targeted agents (hazard ratio 3.02, p = 0.003) was the only factor that predicted for improved survival. Two patients experienced post-GKS hemorrhage within the treated volume. Conclusions Targeted agents appear to improve local control and overall survival in patients treated with GKS for metastastic RCC.

scholarly journals P0350THE DURATION OF PROTEINURIA REMISSION AND CLINICAL OUTCOMES IN IGA NEPHROPATHY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Mark Canney ◽  
Sean Barbour ◽  
Sophia Zheng ◽  
Rosanna Coppo ◽  
Hong Zhang ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Disease Progression ◽  
Iga Nephropathy ◽  
Primary Outcome ◽  
Hazard Ratio ◽  
Surrogate Outcome ◽  
Therapeutic Trials ◽  
Non Linear ◽  
Risk Of Disease

Abstract Background and Aims A relative reduction in proteinuria has been proposed as a surrogate outcome for therapeutic trials in IgA nephropathy. It is currently unknown how long a reduction in proteinuria needs to be maintained in order to mitigate the long-term risk of disease progression. To address this knowledge gap we sought to quantify the association between duration of proteinuria remission and the risk of disease progression in IgA nephropathy. Method In this retrospective multi-ethnic international cohort of adult patients with biopsy-proven IgA nephropathy, we defined proteinuria remission based on three criteria: (i) peak proteinuria on/after biopsy ≥1g/day; (ii) an absolute reduction in proteinuria to &lt;1g/day; (iii) a ≥25% reduction in proteinuria from the peak value. The exposure of interest was the total duration of first remission, treated as a time-varying covariate using longitudinal proteinuria measurements. The primary outcome was the occurrence of end-stage kidney disease or a sustained 50% reduction in estimated glomerular filtration rate (eGFR). The association between duration of remission and the primary outcome was visualized using restricted cubic splines, and quantified using extended Cox proportional hazards regression models. Results A total of 1864 patients met criteria for remission, which occurred a median of 8.3 months after biopsy (IQR 3.6-22). They had a median age of 36.8 (IQR 29.4-46.6) years and a median eGFR of 78 (IQR 55-104) mL/min/1.73m2. Median proteinuria was 1.54 (IQR 1.09-2.4) g/day at the time of biopsy and 0.55 (IQR 0.33-0.76) g/day at the time of entering remission. During a median follow-up of 3.9 years, 274 patients (14.7%) experienced the primary outcome. The relationship between duration of proteinuria remission and the primary outcome was non-linear (Figure). Each 3 months in sustained remission up to 51 months was associated with an additional 9% reduction in the risk of disease progression (hazard ratio 0.91, 95% confidence interval 0.89-0.93). In contrast, each additional 3 months in remission beyond 51 months was associated with a smaller non-significant risk reduction (hazard ratio 0.99, 95% confidence interval 0.96-1.03). These finding were robust to multivariable adjustment and were consistent across subgroups based on the MEST histology score, and whether or not the remission occurred while on renin-angiotensin-aldosterone-system blockade or after immunosuppression treatment. Results were similar when relapse was defined as either a 50% or 100% increase in proteinuria from the nadir value after remission to an absolute value of ≥1g/day. Conclusion We observed a strong non-linear dose-response relationship between the duration of proteinuria remission and the risk of disease progression in patients with IgA nephropathy. The ability to quantitate the renal survival benefit related to the duration of remission is an important advance for patients and their physicians. Rather than there being a minimum duration of proteinuria remission in IgA nephropathy, our results demonstrate that even short durations in remission, or small increases in remission duration, are both associated with significant reductions in the risk of disease progression. For future therapeutic trials in IgA nephropathy using proteinuria as a surrogate outcome, our findings illustrate the need to consider the duration of proteinuria reduction, in addition to the magnitude of proteinuria reduction, when evaluating the anticipated treatment effect on long-term clinical endpoints.

scholarly journals Effect of F-18 Fluorodeoxyglucose Uptake by Bone Marrow on the Prognosis of Head and Neck Squamous Cell Carcinoma

2019 ◽  
Vol 8 (8) ◽  
pp. 1169 ◽  
Author(s):  
Jeong Won Lee ◽  
Myung Jin Ban ◽  
Jae Hong Park ◽  
Sang Mi Lee
Keyword(s):  
Disease Progression ◽  
Primary Tumor ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
Hazard Ratio ◽  
Free Survival ◽  
Fdg Uptake ◽  
Distant Failure ◽  
Pet Ct

The purpose of this study was to assess the relationship between F-18 fluorodeoxyglucose (FDG) uptake in bone marrow (BM) on positron emission tomography/computed tomography (PET/CT) and survival in patients with head and neck squamous cell carcinoma (HNSCC). We retrospectively enrolled 157 HNSCC patients who underwent staging FDG PET/CT and subsequent treatment. On PET/CT, primary tumor metabolic characteristics, mean FDG uptake of BM (BM SUV), and BM-to-liver uptake ratio (BLR) were measured. The prognostic significance of FDG uptake of BM for predicting disease progression-free survival and distant failure-free survival was assessed using a Cox proportional hazards regression model. In univariate analysis for disease progression-free survival, increased BM SUV and BLR were associated with poor survival. In multivariate analysis, BLR (p = 0.044; hazard ratio, 1.96), TNM stage (p = 0.014; hazard ratio, 2.87) and maximum FDG uptake of the primary tumor (p = 0.046; hazard ratio, 2.38) were independently associated with disease progression-free survival. For distant failure-free survival, BLR, TNM stage, tumor size, and metabolic parameters of the primary tumor showed prognostic significance in univariate analysis. However, none of the variables showed significance in multivariate analysis. FDG uptake of BM in HNSCC patients might be a significant predictor for disease progression-free survival. Further studies with large patient population are needed to validate the results.

RADT-01. COMPARATIVE STUDY OF LOCAL CONTROL FOR BRAIN METASTASIS BETWEEN PRE-FRAME AND POST-FRAME MRI METHODS OF GAMMA KNIFE STEREOTACTIC RADIOSURGERY

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi40-vi41
Author(s):  
Yusuki Hori ◽  
Peter Felton ◽  
Ahmet Atik ◽  
Wei Wei ◽  
Alireza Mohammadi ◽  
...  
Keyword(s):  
Brain Metastasis ◽  
Gamma Knife ◽  
Local Control ◽  
Cumulative Incidence ◽  
Multivariable Analysis ◽  
Frailty Model ◽  
Local Failure ◽  
Maximum Diameter ◽  
Significant Prognostic Factor ◽  
Significant Difference

Abstract INTRODUCTION Gamma Knife radiosurgery (GKRS) is an established treatment modality in the management of brain metastasis (BM). The standard treatment flow includes frame placement followed by obtaining a post-frame MRI for planning. However, there has been a shift in practice towards using the pre-frame MRI method. It shortens the frame-wearing time while improving quality of imaging/targeting by decreasing artifacts by screws. However, no previous studies have compared the GKRS outcome between the pre- and post-frame MRI methods. METHODS 134 patients (61 pre-frame and 73 post-frame) with 307 BMs treated with first time GKRS were reviewed retrospectively. We defined local failure (LF) as ≥ 20% increase in maximum diameter (RECIST criteria). Kaplan-Meier and Gray’s method were used to estimate and compare cumulative incidence rate of LF between the groups; multivariable analysis for time-to-local failure (TTLF) was performed using Cox frailty model. The number of lesions was intrinsically modeled in frailty model. RESULTS There was no significant difference between the groups for background variables including age, gender, primary cancer, performance status, and number of lesions. Post-frame group had significantly smaller tumors at baseline (p=0.004). The cumulative incidence rates of LF for pre- vs post-frame groups were 1.6% vs 5.5% at 6 month, 6.9% vs 9.9% at 12 month, and 10.4% vs 17.4% at 24 month, respectively, without significant differences (p=0.84). Using multivariate frailty Cox model adjusting for age, gender, and lesion size, extracranial metastasis (HR 4.13, 95%CI 1.48‒11.57, p=0.007) was the significant prognostic factor for TTLF, while the frame type was not significant (p=0.46). CONCLUSIONS This is the first report comparing the GKRS outcome of pre- and post-frame MRI methods. The results indicated that pre-frame MRI method conveys a comparable local control for BM while maintaining practical benefits such as shortened frame-wearing time, less-artifact imaging, and longer preparation time available for planning.

Systemic sclerosis portends increased risk of conduction and rhythm abnormalities at diagnosis and during disease course: A US population-based cohort

2021 ◽  
pp. 239719832110340
Author(s):  
Yasser A Radwan ◽  
Reto D Kurmann ◽  
Avneek S Sandhu ◽  
Edward A El-Am ◽  
Cynthia S Crowson ◽  
...  
Keyword(s):  
Risk Factors ◽  
Pulmonary Hypertension ◽  
Systemic Sclerosis ◽  
Confidence Interval ◽  
Cumulative Incidence ◽  
Disease Onset ◽  
Population Based ◽  
Hazard Ratio ◽  
Conduction Disorders ◽  
Increased Risk

Objectives: To study the incidence, risk factors, and outcomes of conduction and rhythm disorders in a population-based cohort of patients with systemic sclerosis versus nonsystemic sclerosis comparators. Methods: An incident cohort of patients with systemic sclerosis (1980–2016) from Olmsted County, MN, was compared to age- and sex-matched nonsystemic sclerosis subjects (1:2). Electrocardiograms, Holter electrocardiograms, and a need for cardiac interventions were reviewed to determine the occurrence of any conduction or rhythm abnormalities. Results: Seventy-eight incident systemic sclerosis cases and 156 comparators were identified (mean age 56 years, 91% female). The prevalence of any conduction disorder before systemic sclerosis diagnosis compared to nonsystemic sclerosis subjects was 15% versus 7% ( p = 0.06), and any rhythm disorder was 18% versus 13% ( p = 0.33). During a median follow-up of 10.5 years in patients with systemic sclerosis and 13.0 years in nonsystemic sclerosis comparators, conduction disorders developed in 25 patients with systemic sclerosis with cumulative incidence of 20.5% (95% confidence interval: 12.4%–34.1%) versus 28 nonsystemic sclerosis patients with cumulative incidence of 10.4% (95% confidence interval: 6.2%–17.4%) (hazard ratio: 2.57; 95% confidence interval: 1.48–4.45), while rhythm disorders developed in 27 patients with systemic sclerosis with cumulative incidence of 27.3% (95% confidence interval: 17.9%–41.6%) versus 43 nonsystemic sclerosis patients with cumulative incidence of 18.0% (95% confidence interval: 12.3%–26.4%) (hazard ratio: 1.62; 95% confidence interval: 1.00–2.64). Age, pulmonary hypertension, and smoking were identified as risk factors. Conclusion: Patients with systemic sclerosis have an increased risk of conduction and rhythm disorders both at disease onset and over time, compared to nonsystemic sclerosis patients. These findings warrant increased vigilance and screening for electrocardiogram abnormalities in systemic sclerosis patients with pulmonary hypertension.

scholarly journals Radiation Therapy Improves Local Control in Juvenile Nasopharyngeal Angiofibroma following Disease Progression after Embolization and Surgical Resection: A Case Report

2021 ◽  
pp. 739-745
Author(s):  
Zane Blank ◽  
Richard Sleightholm ◽  
Beth Neilsen ◽  
Michael Baine ◽  
Chi Lin
Keyword(s):  
Radiation Therapy ◽  
Disease Progression ◽  
Surgical Resection ◽  
Local Control ◽  
Benign Neoplasm ◽  
Good Prognosis ◽  
Juvenile Nasopharyngeal Angiofibroma ◽  
Adjuvant Radiation ◽  
Nasopharyngeal Angiofibroma ◽  
Presenting Symptoms

Juvenile nasopharyngeal angiofibroma (JNA) is a relatively uncommon, benign neoplasm of the nasopharynx that can be very difficult to diagnose early due to inconspicuous and seemingly harmless presenting symptoms. Early diagnosis and treatment of JNA are essential for a good prognosis. JNA typically responds well to radiation therapy (RT), but when it does not, the most appropriate next course of action has not been readily defined due to the limited occurrence and experience with this neoplasm. Herein, we describe a JNA patient, who continued to progress after surgery and 36 Gy of adjuvant radiation, but after an additional 14.4 Gy, he has remained in remission for over 2 years. An 11-year-old boy who presented with JNA underwent treatment with embolization and surgical resection. Unfortunately, the tumor progressed within 2 months of surgical intervention and he required RT for adequate local control. While undergoing RT, he again demonstrated signs of progression; so his radiation regimen was increased from 3,600 cGy in 20 fractions to 5,040 cGy in 28 fractions. Since completing RT, the tumor has continued to decrease in size, and the patient is stable and has been without signs of disease progression for over 24 months now. Thus, escalating the radiation regimen to 5,040 cGy may improve local control in rapidly progressive JNA.

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