Browsing by Author "Seward, Shelly M."

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    Effects of Slide Storage on Detection of Molecular Markers by IHC and FISH in Endometrial Cancer Tissues From a Clinical Trial: An NRG Oncology/GOG Pilot Study
    (Wolters Kluwer, 2022) Grushko, Tatyana A.; Filiaci, Virginia L.; Montag, Anthony G.; Apushkin, Marsha; Gomez, Maria J.; Monovich, Laura; Ramirez, Nilsa C.; Schwab, Carlton; Kesterson, Joshua P.; Seward, Shelly M.; Method, Michael W.; Olopade, Olufunmilayo I.; Fleming, Gini F.; Birrer, Michael J.; Medicine, School of Medicine
    We performed a pilot study in anticipation of using long-aged precut formalin fixed paraffin embedded (FFPE) tissue sections stored in real-world conditions for translational biomarker studies of TOP2A, Ki67, and HER2 in endometrial cancer. FFPE tissue blocks or unstained slides or both from GOG-0177 were collected centrally (1999-2000) and stored at room temperature. During 2004-2011 specimens were stored at 4°C. Matched pairs of stored slides and freshly cut slides from stored blocks were analyzed for TOP2A (KiS1), Ki67 (MIB1) and HER2 (Herceptest™) proteins. To assess DNA stability (HER2 PathVision), FISH was repeated on stored slides from 21 cases previously shown to be HER2-amplified. IHC staining intensity and extent, mean FISH copies/cell, and copy number ratios were compared using the kappa statistic for concordance or signed rank test for differences in old cut versus new cut slides. IHC results reflected some protein degradation in stored slides. The proportion of cells with TOP2A staining was lower on average by 12% in older sections (p=.03). The proportion of Ki67 positive cells was lower in stored slides by an average of 10% (p<.01). Too few cases in the IHC cohort were FISH positive for any conclusions. HER2 amplification by FISH was unaffected by slide storage. We conclude that use of aged stored slides for proliferation markers TOP2A and Ki67 is feasible but may modestly underestimate true values in endometrial cancer. Pilot studies for particular storage conditions/durations/antigens to be used in translational studies are warranted.
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    Is age a prognostic biomarker for survival among women with locally advanced cervical cancer treated with chemoradiation? An NRG Oncology/Gynecologic Oncology Group ancillary data analysis
    (Elsevier, 2016-11) Moore, Kathleen N.; Java, James J.; Slaughter, Katrina N.; Rose, Peter G.; Lanciano, Rachelle; DiSilvestro, Paul A.; Thigpen, J. Tate; Lee, Yi-Chun; Tewari, Krishnansu S.; Chino, Junzo; Seward, Shelly M.; Miller, David S.; Salani, Ritu; Moore, David H.; Stehman, Frederick B.; Obstetrics and Gynecology, School of Medicine
    Objective To determine the effect of age on completion of and toxicities following treatment of local regionally advanced cervical cancer (LACC) on Gynecologic Oncology Group (GOG) Phase I–III trials. Methods An ancillary data analysis of GOG protocols 113, 120, 165, 219 data was performed. Wilcoxon, Pearson, and Kruskal-Wallis tests were used for univariate and multivariate analysis. Log rank tests were used to compare survival lengths. Results One-thousand-three-hundred-nineteen women were included; 60.7% were Caucasian, 15% were age 60–70 years and an additional 5% were >70; 87% had squamous histology, 55% had stage IIB disease and 34% had IIIB disease. Performance status declined with age (p = 0.006). Histology and tumor stage did not significantly differ., Number of cycles of chemotherapy received, radiation treatment time, nor dose modifications varied with age. Notably, radiation protocol deviations and failure to complete brachytherapy (BT) did increase with age (p = 0.022 and p < 0.001 respectively)., Only all grade lymphatic (p = 0.006) and grade ≥3 cardiovascular toxicities (p= 0.019) were found to vary with age., A 2% increase in the risk of death for every year increase >50 for all-cause mortality (HR 1.02; 95% CI, 1.01–1.04) was found, but no association between age and disease specific mortality was found. Conclusion This represents a large analysis of patients treated for LACC with chemo/radiation, approximately 20% of whom were >60 years of age. Older patients, had higher rates of incomplete brachytherapy which is not explained by collected toxicity data. Age did not adversely impact completion of chemotherapy and radiation or toxicities.