- Browse by Subject
Browsing by Subject "Kaplan-Meier estimate"
Now showing 1 - 2 of 2
Results Per Page
Sort Options
Item Effects of low-dose estrogen replacement during childhood on pubertal development and gonadotropin concentrations in patients with Turner syndrome: results of a randomized, double-blind, placebo-controlled clinical trial(The Endocrine Society, 2014-09) Quigley, Charmian A.; Wan, Xiaohai; Garg, Sipi; Kowal, Karen; Cutler, Gordon B. Jr.; Ross, Judith L.; Department of Medicine, IU School of MedicineCONTEXT: The optimal approach to estrogen replacement in girls with Turner syndrome has not been determined. OBJECTIVE: The aim of the study was to assess the effects of an individualized regimen of low-dose ethinyl estradiol (EE2) during childhood from as early as age 5, followed by a pubertal induction regimen starting after age 12 and escalating to full replacement over 4 years. DESIGN: This study was a prospective, randomized, double-blind, placebo-controlled clinical trial. SETTING: The study was conducted at two US pediatric endocrine centers. SUBJECTS: Girls with Turner syndrome (n = 149), aged 5.0-12.5 years, were enrolled; data from 123 girls were analyzable for pubertal onset. INTERVENTION(S): Interventions comprised placebo or recombinant GH injections three times a week, with daily oral placebo or oral EE2 during childhood (25 ng/kg/d, ages 5-8 y; 50 ng/kg/d, ages >8-12 y); after age 12, all patients received escalating EE2 starting at a nominal dosage of 100 ng/kg/d. Placebo/EE2 dosages were reduced by 50% for breast development before age 12 years, vaginal bleeding before age 14 years, or undue advance in bone age. MAIN OUTCOME MEASURES: The main outcome measures for this report were median ages at Tanner breast stage ≥2, median age at menarche, and tempo of puberty (Tanner 2 to menarche). Patterns of gonadotropin secretion and impact of childhood EE2 on gonadotropins also were assessed. RESULTS: Compared with recipients of oral placebo (n = 62), girls who received childhood low-dose EE2 (n = 61) had significantly earlier thelarche (median, 11.6 vs 12.6 y, P < 0.001) and slower tempo of puberty (median, 3.3 vs 2.2 y, P = 0.003); both groups had delayed menarche (median, 15.0 y). Among childhood placebo recipients, girls who had spontaneous breast development before estrogen exposure had significantly lower median FSH values than girls who did not. CONCLUSIONS: In addition to previously reported effects on cognitive measures and GH-mediated height gain, childhood estrogen replacement significantly normalized the onset and tempo of puberty. Childhood low-dose estrogen replacement should be considered for girls with Turner syndrome.Item Ninety Percent or Greater Tumor Necrosis Is Associated With Survival and Social Determinants of Health in Patients With Osteosarcoma in the National Cancer Database(Wolters Kluwer, 2023) Richardson, Spencer M.; Wurtz, L. Daniel; Collier, Christopher D.; Orthopaedic Surgery, School of MedicineBackground: The histologic response of osteosarcoma to chemotherapy is commonly cited as a prognostic factor and typically graded as the percent necrosis of the tumor at the time of surgical resection. Few studies, to our knowledge, have examined the relationship of tumor necrosis relative to other factors. Existing studies are limited by prolonged enrollment periods or analysis of patient subsets without the strongest predictor of mortality: metastasis at diagnosis. Additionally, the definitive threshold value for a good histologic response is commonly set at more than 90% tumor necrosis with little evidence; some authors advocate other values. Question/purposes: (1) Are there alternative cutoff values for a good response to chemotherapy in a large, national cohort of contemporarily treated patients with osteosarcoma? (2) How does the association of histologic response to survival in osteosarcoma compare with other clinicopathologic factors? (3) What patient and clinical factors are associated with the histologic response? Methods: We identified 2006 patients with osteosarcoma diagnosed between 2010 and 2015 in the National Cancer Database (NCDB), a registry that includes 70% of all new cancers diagnosed in the United States with 90% follow-up. Patients were excluded for missing documentation of percent tumor necrosis (21% [425 of 2006]) or if definitive resection was not performed (< 1% [1 of 2006]). A total of 1580 patients were included in the analysis, with a mean follow-up duration of 37 ± 22 months. A Kaplan-Meier survival analysis, stratified by the percent tumor necrosis after chemotherapy, was performed for the 5-year period. Other covariates examined were sex, race, socioeconomic score composite, insurance type, Charlson/Deyo score, distance from the hospital, and location (metropolitan, urban, or rural). Clinical and sociodemographic data including patient-identified race from the patient's medical record is input into the NCDB by certified registrars. The NCDB only allows coding of one primary race for each patient; thus, most of our patients were grouped as White or Black race and the remaining were grouped as Other for our analysis. A multiple Cox regression analysis was performed to evaluate the effect of percent necrosis compared with other demographic, clinicopathologic, and treatment effects on survival. Finally, a multiple logistic regression analysis was performed to assess demographic and clinicopathologic characteristics associated with percent necrosis. Results: Five-year overall survival for patients with histologic gradings of 90% to 94% necrosis (70% [95% confidence interval (CI) 60.6% to 79.7%) and 95% to 100% necrosis (74% [95% CI 68% to 80.3%) was not different between groups (p = 0.47). A comparison of histologic responses below 90% necrosis found no difference in survival between patients with decreasing histologic response (p > 0.05). Necrosis of less than 90% was associated with worse survival (HR 2.00 [95% CI 1.58 to 2.52]; p < 0.001 compared with more than 90% necrosis), and factors most associated with poor survival were metastasis (HR 2.85 [95% CI 2.27 to 3.59]; p < 0.001) and skip metastasis at the time of diagnosis (HR 2.52 [95% CI 1.64 to 3.88]; p < 0.001). On multivariate analysis, adjusting for demographic, clinicopathologic, and treatment factors, social determinants of health were negatively associated with percent necrosis of 90% or more, including uninsured status (OR 0.46 [95% CI 0.23 to 0.92]; p = 0.02 compared with private insurance) and lower socioeconomic status composite (OR for the lowest first and second quartiles were 0.63 [95% CI 0.44 to 0.90]; p = 0.01 and 0.70 [95% CI 0.50 to 0.96]; p = 0.03, respectively). Race other than White or Black (OR 0.61 [95% CI 0.40 to 0.94]; p = 0.02 compared with White race) was also negatively associated with percent necrosis of more than 90% after controlling for available covariates. Conclusion: This study suggests that a cutoff of 90% necrosis provides the best prognostic value for patients with osteosarcoma undergoing chemotherapy. Other threshold values did not show different survival benefits. Sociodemographic factors were associated with histologic response less than 90%. These associations must be carefully understood not as cause and effect but likely demonstrating the effects of health disparities and access to care. Although we controlled for multiple variables in our analysis, broad variables such as race may have been associated with histologic response due to unaccounted confounders. Medical providers should be aware of these associations to ensure equitable access and delivery of care because access to care may be responsible for these associations. Future studies should examine potential drivers of this observation, such as a delay in presentation or deviation from standard of care practices.