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Item Author Correction: Inhibitory effects of dopamine receptor D1 agonist on mammary tumor and bone metastasis(Springer Nature, 2022-11-03) Minami, Kazumasa; Liu, Shengzhi; Liu, Yang; Chen, Andy; Wan, Qiaoqiao; Na, Sungsoo; Li, Bai‑Yan; Matsuura, Nariaki; Koizumi, Masahiko; Yin, Yukun; Gan, Liangying; Xu, Aihua; Li, Jiliang; Nakshatri, Harikrishna; Yokota, Hiroki; Biomedical Engineering, School of Engineering and TechnologyThis corrects the article "Inhibitory Effects of Dopamine Receptor D1 Agonist on Mammary Tumor and Bone Metastasis" in volume 7, 45686. doi: 10.1038/srep45686Item Do Surgical Margins Affect Local Recurrence and Survival in Extremity, Nonmetastatic, High-grade Osteosarcoma?(Springer, 2016-03) Bertrand, Todd E.; Cruz, Alex; Binitie, Odion; Cheong, David; Letson, G. Douglas; Department of Orthopaedic Surgery, IU School of MedicineBACKGROUND: Long-term survival for all patients with osteosarcoma using current aggressive adjuvant chemotherapy and surgical resection is between 60% and 70%. In patients who present with nonmetastatic, high-grade extremity osteosarcoma of bone, limb salvage surgery is favored, when appropriate, over amputation to preserve the limb, because limb salvage may lead to a superior quality of life compared with amputation. However, concern remains that in the attempt to preserve the limb, close or microscopically positive surgical margins may have an adverse effect on event-free survival. QUESTIONS/PURPOSES: (1) Does a positive or close surgical margin increase the likelihood of a local recurrence? (2) Does a positive or close surgical margin adversely affect the development of metastatic disease? (3) What is the relationship of surgical margin on overall survival? METHODS: With institutional review board approval, we retrospectively evaluated 241 patients treated at our institution between 1999 and 2011. Exclusion criteria included nonextremity locations, metastatic disease at initial presentation, low- or intermediate-grade osteosarcoma, treatment regimens that did not follow National Comprehensive Cancer Network (NCCN) guidelines, incomplete medical records, and any part of treatment performed outside of Moffitt Cancer Center or All Children's Hospital. Fifty-one patients were included in the final analysis, of whom 31 (61%) had followup data at a minimum of 2 years or whose clinical status was known but had died before 2 years of followup. Margin status was defined as (1) microscopically positive; (2) negative ≤ 1 mm; and (3) negative > 1 mm. Margin status, histologic response (tumor percent necrosis), type of osteosarcoma, type of surgery, presence of local recurrence, metastatic disease, and overall survival were recorded for each patient. The mean age was 22 years (range, 12-74 years) and the mean followup was 3 years (range, 0.1-14 years). Margin status was positive in 10% (five of 51), negative ≤ 1 mm 26% (13 of 51), and negative > 1 mm 65% (33 of 51). RESULTS: Local recurrence was noted to be 14% (seven of 51) at 3.4 years. After controlling for relevant confounding variables, the presence of a positive margin compared with a negative margin > 1 mm was the only independent predictor of local recurrence (hazard ratio [HR], 8.006; 95% confidence interval [CI], 1.314-48.781; p = 0.0241). At a mean of 3.4 years, 29% (15 of 51) of the patients developed metastatic disease with no difference with the numbers available in the probability of developing metastatic disease among the three margin groups (p = 0.614). Overall survival at 3.8 years was 75% (38 of 51). After controlling for relevant confounding variables, we found that patients with positive margins were more likely to die from disease than those with negative margins (HR, 6.26; 95% CI, 1.50-26.14; p = 0.0119); no other independent predictors of survival were identified. CONCLUSIONS: With the numbers of patients we had, we observed that patients with extremity, nonmetastatic, high-grade osteosarcoma who had positive margins showed a higher probability of local recurrence in comparison to those with negative surgical margins. Given that positive margins appear to be associated with poorer survival in patients with high-grade osteosarcoma of the extremities, surgeons should strive to achieve negative margins, but larger studies are needed to confirm these findings. LEVEL OF EVIDENCE: Level III, therapeutic study.Item Intracardiac extension of chondroblastic osteosarcoma(Oxford University Press, 2021) Madison, Mackenzie K.; Matthews, Caleb R.; Lee, Lawrence S.; Surgery, School of MedicineIntravascular tumour extension invading the intracardiac space is rarely seen with osteosarcoma. We present a patient with a history of previously resected pelvic osteosarcoma who was later found to have a local recurrence with continuous intravascular extension from the right femoral vein to the right atrium. Preoperative imaging studies initially described extensive thrombus burden, and a multidisciplinary approach involving open and percutaneous thrombectomy was planned. Intraoperative inspection and pathological analysis revealed unresectable malignant solid tumour rather than thrombus. Though exceedingly rare, the possibility of metastatic tumour must be considered when planning treatment strategies for these patients.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.