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Browsing by Author "Roshal, Anna"
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Item Immunogenomic profiling and pathological response results from a clinical trial of docetaxel and carboplatin in triple negative breast cancer(Springer, 2021) Ademuyiwa, Foluso O.; Chen, Ina; Luo, Jingqin; Rimawi, Mothaffar F.; Hagemann, Ian S.; Fisk, Bryan; Jeffers, Gejae; Skidmore, Zachary L.; Basu, Anamika; Richters, Megan; Ma, Cynthia X.; Weilbaecher, Katherine; Davis, Jennifer; Suresh, Rama; Peterson, Lindsay L.; Bose, Ron; Bagegni, Nusayba; Rigden, Caron E.; Frith, Ashley; Rearden, Timothy P.; Hernandez-Aya, Leonel F.; Roshal, Anna; Clifton, Katherine; Opyrchal, Mateusz; Akintola-Ogunremi, Olaronke; Lee, Byung Ha; Ferrando-Martinez, Sara; Church, Sarah E.; Anurag, Meenakshi; Ellis, Matthew J.; Gao, Feng; Gillanders, William; Griffith, Obi L.; Griffith, Malachi; Medicine, School of MedicinePurpose: Patients with triple-negative breast cancer (TNBC) who do not achieve pathological complete response (pCR) following neoadjuvant chemotherapy have a high risk of recurrence and death. Molecular characterization may identify patients unlikely to achieve pCR. This neoadjuvant trial was conducted to determine the pCR rate with docetaxel and carboplatin and to identify molecular alterations and/or immune gene signatures predicting pCR. Experimental design: Patients with clinical stages II/III TNBC received 6 cycles of docetaxel and carboplatin. The primary objective was to determine if neoadjuvant docetaxel and carboplatin would increase the pCR rate in TNBC compared to historical expectations. We performed whole-exome sequencing (WES) and immune profiling on pre-treatment tumor samples to identify alterations that may predict pCR. Thirteen matching on-treatment samples were also analyzed to assess changes in molecular profiles. Results: Fifty-eight of 127 (45.7%) patients achieved pCR. There was a non-significant trend toward higher mutation burden for patients with residual cancer burden (RCB) 0/I versus RCB II/III (median 80 versus 68 variants, p 0.88). TP53 was the most frequently mutated gene, observed in 85.7% of tumors. EGFR, RB1, RAD51AP2, SDK2, L1CAM, KPRP, PCDHA1, CACNA1S, CFAP58, COL22A1, and COL4A5 mutations were observed almost exclusively in pre-treatment samples from patients who achieved pCR. Seven mutations in PCDHA1 were observed in pre-treatment samples from patients who did not achieve pCR. Several immune gene signatures including IDO1, PD-L1, interferon gamma signaling, CTLA4, cytotoxicity, tumor inflammation signature, inflammatory chemokines, cytotoxic cells, lymphoid, PD-L2, exhausted CD8, Tregs, and immunoproteasome were upregulated in pre-treatment samples from patients who achieved pCR. Conclusion: Neoadjuvant docetaxel and carboplatin resulted in a pCR of 45.7%. WES and immune profiling differentiated patients with and without pCR.Item Isolated Kaposi sarcoma of the upper aerodigestive tract in immunocompetent individuals, an underrecognized entity with favorable prognosis(Sage, 2022-09-15) Shabaan, Abdelrahman; Alkashash, Ahmad; Hou, Tieying; Saeed, Omer; Yesensky, Jessica; Roshal, Anna; Mesa, Hector; Otolaryngology -- Head and Neck Surgery, School of MedicineKaposi sarcoma (KS) is a rare vascular neoplasm that most commonly arises in the setting of immunosuppression, in areas with high prevalence of Human Herpesvirus-8 infection, and when both situations coexist. Most cases affect the skin, isolated involvement of the upper respiratory tract without skin involvement is extremely rare with only a few cases reported in the literature. We present a case of isolated nasopharyngeal KS in an immunocompetent patient who achieved remission after multimodality therapy. Recent advances in KS-therapy are discussed.