Publications by authors named "Sneha R Rao"

4 Publications

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Extent of tumor fibrosis/hyalinization and infarction following neoadjuvant radiation therapy is associated with improved survival in patients with soft-tissue sarcoma.

Cancer Med 2022 01 27;11(1):194-206. Epub 2021 Nov 27.

Department of Orthopaedics, Duke University, Durham, North Carolina, USA.

Introduction: Current standard of care for most intermediate and high-grade soft-tissue sarcomas (STS) includes limb-preserving surgical resection with either neoadjuvant radiation therapy (NRT) or adjuvant radiation therapy. To date, there have been a few studies that attempt to correlate histopathologic response to NRT with oncologic outcomes in patients with STS.

Methods: Using our institutional database, we identified 58 patients who received NRT followed by surgical resection for primary intermediate or high-grade STS and 34 patients who received surgical resection without NRT but did receive adjuvant radiation therapy or did not receive any radiation therapy. We analyzed four histologic parameters of response to therapy: residual viable tumor, fibrosis/hyalinization, necrosis, and infarction (each ratiometrically determined). Data were stratified into two binary groups. Unadjusted, 5- and 10-year overall survival, and relapsed-free survival (RFS) were calculated using the Kaplan-Meier method.

Results: Analysis of pathologic characteristics showed that patients treated with NRT demonstrate significantly higher tumor infarction, higher tumor fibrosis/hyalinization, and a lower percent viable tumor compared with patients not treated with NRT (p < 0.0001). Based on Kaplan-Meier curve analysis and multivariate cox proportional hazard model for OS and RFS, patients treated with NRT and showing >12.5% tumor fibrosis/hyalinization have significantly higher overall survival and recurrence-free survival at 5 and 10 years.

Discussion And Conclusion: We have identified three histopathologic characteristics-fibrosis, hyalinization, and infarction-that may serve as predictive biomarkers of response to NRT for STS patients. Future prospective studies will be needed to confirm this association.
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http://dx.doi.org/10.1002/cam4.4428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8704179PMC
January 2022

From the Clinic to the Bench and Back Again in One Dog Year: How a Cross-Species Pipeline to Identify New Treatments for Sarcoma Illuminates the Path Forward in Precision Medicine.

Front Oncol 2020 11;10:117. Epub 2020 Feb 11.

Department of Orthopaedic Surgery, Duke University Medical Center, Durham, NC, United States.

Cancer drug discovery is an inefficient process, with more than 90% of newly-discovered therapies failing to gain regulatory approval. Patient-derived models of cancer offer a promising new approach to identify new treatments; however, for rare cancers, such as sarcomas, access to patient samples is limited, which precludes development of patient-derived models. To address the limited access to patient samples, we have turned to pet dogs with naturally-occurring sarcomas. Although sarcomas make up <1% of all human cancers, sarcomas represent 15% of cancers in dogs. Because dogs have similar immune systems, an accelerated pace of cancer progression, and a shared environment with humans, studying pet dogs with cancer is ideal for bridging gaps between mouse models and human cancers. Here, we present our cross-species personalized medicine pipeline to identify new therapies for sarcomas. We explore this process through the focused study of a pet dog, Teddy, who presented with six synchronous leiomyosarcomas. Using our pipeline we identified proteasome inhibitors as a potential therapy for Teddy. Teddy was treated with bortezomib and showed a varied response across tumors. Whole exome sequencing revealed substantial genetic heterogeneity across Teddy's recurrent tumors and metastases, suggesting that intra-patient heterogeneity and tumoral adaptation were responsible for the heterogeneous clinical response. Ubiquitin proteomics coupled with exome sequencing revealed multiple candidate driver mutations in proteins related to the proteasome pathway. Together, our results demonstrate how the comparative study of canine sarcomas offers important insights into the development of personalized medicine approaches that can lead to new treatments for sarcomas in both humans and canines.
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http://dx.doi.org/10.3389/fonc.2020.00117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7026496PMC
February 2020

Polymicrobial Infections in Hip Arthroplasty: Lower Treatment Success Rate, Increased Surgery, and Longer Hospitalization.

J Arthroplasty 2019 04 9;34(4):710-716.e3. Epub 2018 Oct 9.

Department of Orthopaedic Surgery, Duke University Medical Center, Durham, NC.

Background: Polymicrobial hip arthroplasty infections are a subset of periprosthetic joint infection (PJI) with distinct challenges representing 10%-47% of PJI.

Methods: Records were reviewed from all PJIs involving partial or total hip arthroplasty with positive hip cultures between 2005 and 2015 in order to determine baseline characteristics and outcomes including treatment success, surgeries for infection, and days in hospital for infection. Analysis was restricted to patients who had at least 2 years of follow-up after their final surgery or hospitalization for infection. Factors with P-value less than .05 in univariate outcomes analysis were included in multivariable models.

Results: After multivariable analysis, 28 of 95 hip arthroplasty PJIs which were polymicrobial were associated with significantly lower treatment success, more surgery, and longer hospitalizations compared to PJIs which were not polymicrobial. Patients diagnosed with polymicrobial infection later in treatment (4 of 28) had the lowest treatment success rate, underwent the most surgery, and spent the longest time in hospital.

Conclusion: Polymicrobial periprosthetic hip infection is a particularly devastating complication of hip arthroplasty associated with decreased likelihood of treatment success, increased surgery for infection, and greater time in hospital. Patients with late polymicrobial infection had the worst outcomes. This investigation further characterizes the natural history of periprosthetic hip infections with more than one infectious organism. Patients who present with a subsequent polymicrobial infection should be educated that they have a particularly difficult treatment course and treatment success may not be possible.
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http://dx.doi.org/10.1016/j.arth.2018.09.090DOI Listing
April 2019

The "Fingerprint" of Cancer Extends Beyond Solid Tumor Boundaries: Assessment With a Novel Ultrasound Imaging Approach.

IEEE Trans Biomed Eng 2016 05 18;63(5):1082-6. Epub 2015 Sep 18.

Goal: Abnormalities of microvascular morphology have been associated with tumor angiogenesis for more than a decade, and are believed to be intimately related to both tumor malignancy and response to treatment. However, the study of these vascular changes in-vivo has been challenged due to the lack of imaging approaches which can assess the microvasculature in 3-D volumes noninvasively. Here, we use contrast-enhanced "acoustic angiography" ultrasound imaging to observe and quantify heterogeneity in vascular morphology around solid tumors.

Methods: Acoustic angiography, a recent advance in contrast-enhanced ultrasound imaging, generates high-resolution microvascular images unlike anything possible with standard ultrasound imaging techniques. Acoustic angiography images of a genetically engineered mouse breast cancer model were acquired to develop an image acquisition and processing routine that isolated radially expanding regions of a 3-D image from the tumor boundary to the edge of the imaging field for assessment of vascular morphology of tumor and surrounding vessels.

Results: Quantitative analysis of vessel tortuosity for the tissue surrounding tumors 3 to 7 mm in diameter revealed that tortuosity decreased in a region 6 to 10 mm from the tumor boundary, but was still significantly elevated when compared to control vasculature.

Conclusion: Our analysis of angiogenesis-induced changes in the vasculature outside the tumor margin reveals that the extent of abnormal tortuosity extends significantly beyond the primary tumor mass.

Significance: Visualization of abnormal vascular tortuosity may make acoustic angiography an invaluable tool for early tumor detection based on quantifying the vascular footprint of small tumors and a sensitive method for understanding changes in the vascular microenvironment during tumor progression.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5070672PMC
http://dx.doi.org/10.1109/TBME.2015.2479590DOI Listing
May 2016
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