- Browse by Author
Browsing by Author "Bertrand, Todd E."
Now showing 1 - 3 of 3
Results Per Page
Sort Options
Item Congenital ichthyosis patient with squamous cell carcinoma of the skin who received concurrent chemoradiation: A case report(Elsevier, 2017-09-05) Cerra-Franco, Alberto; Grethlein, Sara J.; Bertrand, Todd E.; Wooden, William A.; Saito, Naoyuki G.; Radiation Oncology, School of MedicineItem 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 Systems Biology Approach Identifies Prognostic Signatures of Poor Overall Survival and Guides the Prioritization of Novel BET-CHK1 Combination Therapy for Osteosarcoma(MDPI, 2020-08-26) Pandya, Pankita H.; Cheng, Lijun; Saadatzadeh, M. Reza; Bijangi-Vishehsaraei, Khadijeh; Tang, Shan; Sinn, Anthony L.; Trowbridge, Melissa A.; Coy, Kathryn L.; Bailey, Barbara J.; Young, Courtney N.; Ding, Jixin; Dobrota, Erika A.; Dyer, Savannah; Elmi, Adily; Thompson, Quinton; Barghi, Farinaz; Shultz, Jeremiah; Albright, Eric A.; Shannon, Harlan E.; Murray, Mary E.; Marshall, Mark S.; Ferguson, Michael J.; Bertrand, Todd E.; Wurtz, L. Daniel; Batra, Sandeep; Li, Lang; Renbarger, Jamie L.; Pollok, Karen E.; Pediatrics, School of MedicineOsteosarcoma (OS) patients exhibit poor overall survival, partly due to copy number variations (CNVs) resulting in dysregulated gene expression and therapeutic resistance. To identify actionable prognostic signatures of poor overall survival, we employed a systems biology approach using public databases to integrate CNVs, gene expression, and survival outcomes in pediatric, adolescent, and young adult OS patients. Chromosome 8 was a hotspot for poor prognostic signatures. The MYC-RAD21 copy number gain (8q24) correlated with increased gene expression and poor overall survival in 90% of the patients (n = 85). MYC and RAD21 play a role in replication-stress, which is a therapeutically actionable network. We prioritized replication-stress regulators, bromodomain and extra-terminal proteins (BETs), and CHK1, in order to test the hypothesis that the inhibition of BET + CHK1 in MYC-RAD21+ pediatric OS models would be efficacious and safe. We demonstrate that MYC-RAD21+ pediatric OS cell lines were sensitive to the inhibition of BET (BETi) and CHK1 (CHK1i) at clinically achievable concentrations. While the potentiation of CHK1i-mediated effects by BETi was BET-BRD4-dependent, MYC expression was BET-BRD4-independent. In MYC-RAD21+ pediatric OS xenografts, BETi + CHK1i significantly decreased tumor growth, increased survival, and was well tolerated. Therefore, targeting replication stress is a promising strategy to pursue as a therapeutic option for this devastating disease.