Browsing by Subject "Testicular Neoplasms"

Now showing 1 - 7 of 7
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    Chemotherapy-Related Chronic Myelogenous Leukemia: A Case Series of Patients With Germ Cell Tumor
    (American Medical Association, 2016-03) Adra, Nabil; Sayar, Hamid; Einhorn, Lawrence H.; Department of Medicine, IU School of Medicine
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    Prognostic Value of Teratoma in Primary Tumor and Postchemotherapy Retroperitoneal Lymph Node Dissection Specimens in Patients With Metastatic Germ Cell Tumor
    (American Society of Clinical Oncology, 2020-04-20) Taza, Fadi; Chovanec, Michal; Snavely, Anna; Hanna, Nasser H.; Cary, Clint; Masterson, Timothy A.; Foster, Richard S.; Einhorn, Lawrence H.; Albany, Costantine; Adra, Nabil; Medicine, School of Medicine
    Purpose: Presence of teratoma in patients with metastatic testicular germ cell tumor (GCT) is of unknown prognostic significance. We report survival outcomes of patients with or without teratoma in primary tumor and postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) specimen and assess impact on prognosis. Patients and methods: Patients with metastatic nonseminomatous GCT (NSGCT) who were evaluated at Indiana University between 1990 and 2016 and had primary testicular tumor specimen from orchiectomy (ORCH) were included. All patients were treated with cisplatin-based combination chemotherapy. The cohort was divided into 2 groups according to presence or absence of teratoma in ORCH specimen. Survival data were correlated with histopathologic findings. Differences in progression-free (PFS) and overall survival (OS) were evaluated using log-rank tests and Cox proportional hazards models to adjust for known adverse prognostic factors. Results: We identified 1,224 consecutive patients evaluated at Indiana University between 1990 and 2016 who met inclusion criteria. Median age was 27 years (range, 13-71 years); 689 patients had teratoma in ORCH specimen, and 535 did not. With median follow-up of 2.3 years, 5-year PFS was 61.9% (95% CI, 57.1% to 66.2%) for those with teratoma versus 63.1% (95% CI, 58.0% to 67.8%) for those without (P = .66); 5-year OS was 82.2% (95% CI, 77.9% to 85.8%) versus 81.4% (95% CI, 76.5% to 85.3%; P = .91), respectively. A total of 473 patients underwent PC-RPLND; 5-year PFS for patients with pure teratoma in PC-RPLND specimen versus necrosis only was 65.9% versus 79.1% (P = .06), and 5-year OS was 90.3% versus 93.4% (P = .21), respectively. Conclusion: Presence of teratoma in ORCH and PC-RPLND specimens was not a prognostic factor in this large retrospective study of patients with NSGCT.
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    Systemic immune-inflammation index in germ-cell tumours: search for a biological prognostic biomarker
    (Springer Nature, 2018-03-20) Albany, Costantine; Medicine, School of Medicine
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    Variants in WFS1 and Other Mendelian Deafness Genes Are Associated with Cisplatin-Associated Ototoxicity
    (American Association for Cancer Research, 2017-07-01) Wheeler, Heather E.; Gamazon, Eric R.; Frisina, Robert D.; Perez-Cervantes, Carlos; El Charif, Omar; Mapes, Brandon; Fossa, Sophie D.; Feldman, Darren R.; Hamilton, Robert J.; Vaughn, David J.; Beard, Clair J.; Fung, Chunkit; Kollmannsberger, Christian; Kim, Jeri; Mushiroda, Taisei; Kubo, Michiaki; Ardeshir-Rouhani-Fard, Shirin; Einhorn, Lawrence; Cox, Nancy J.; Dolan, M. Eileen; Travis, Lois B.; Medicine, School of Medicine
    Purpose: Cisplatin is one of the most commonly used chemotherapy drugs worldwide and one of the most ototoxic. We sought to identify genetic variants that modulate cisplatin-associated ototoxicity (CAO).Experimental Design: We performed a genome-wide association study (GWAS) of CAO using quantitative audiometry (4-12 kHz) in 511 testicular cancer survivors of European genetic ancestry. We performed polygenic modeling and functional analyses using a variety of publicly available databases. We used an electronic health record cohort to replicate our top mechanistic finding.Results: One SNP, rs62283056, in the first intron of Mendelian deafness gene WFS1 (wolframin ER transmembrane glycoprotein) and an expression quantitative trait locus (eQTL) for WFS1 met genome-wide significance for association with CAO (P = 1.4 × 10-8). A significant interaction between cumulative cisplatin dose and rs62283056 genotype was evident, indicating that higher cisplatin doses exacerbate hearing loss in patients with the minor allele (P = 0.035). The association between decreased WFS1 expression and hearing loss was replicated in an independent BioVU cohort (n = 18,620 patients, Bonferroni adjusted P < 0.05). Beyond this top signal, we show CAO is a polygenic trait and that SNPs in and near 84 known Mendelian deafness genes are significantly enriched for low P values in the GWAS (P = 0.048).Conclusions: We show for the first time the role of WFS1 in CAO and document a statistically significant interaction between increasing cumulative cisplatin dose and rs62283056 genotype. Our clinical translational results demonstrate that pretherapy patient genotyping to minimize ototoxicity could be useful when deciding between cisplatin-based chemotherapy regimens of comparable efficacy with different cumulative doses.