Browsing by Author "Kesterson, Joshua P."

Now showing 1 - 4 of 4
  • Thumbnail Image
    Item
    Disease Extent at Secondary Cytoreductive Surgery is Predictive of Progression-free and Overall Survival in Advanced Stage Ovarian Cancer: an NRG Oncology/Gynecologic Oncology Group study
    (Elsevier, 2016-12) Rose, Peter G.; Java, James J.; Morgan, Mark A.; Secord, Angeles Alvarez; Kesterson, Joshua P.; Stehman, Frederick B.; Warshal, David P.; Creasman, William T.; Hanjani, Parviz; Morris, Robert T.; Copeland, Larry J.; Obstetrics and Gynecology, School of Medicine
    Purpose GOG 152 was a randomized trial of secondary cytoreductive surgery (SCS) in patients with suboptimal residual disease (residual tumor nodule >1 cm in greatest diameter) following primary cytoreductive surgery for advanced stage ovarian cancer. The current analysis was undertaken to evaluate the impact of disease findings at SCS on progression-free survival (PFS) and overall survival (OS). Methods Among the 550 patients enrolled on GOG-152, two-hundred-sixteen patients were randomly assigned following 3 cycles of cisplatin and paclitaxel to receive SCS. In 15 patients (7%) surgery was declined or contraindicated. In the remaining 201 patients the operative and pathology reports were utilized to classify their disease status at the beginning of SCS as; no gross disease/microscopically negative N= 40 (19.9%), no gross disease/microscopically positive N= 8 (4.0%), and gross disease N=153 (76.1%). Results The median PFS for patients with no gross disease/microscopically negative was 16.1 months, no gross disease/microscopically positive was 13.5 months and for gross disease was 11.7 months, p=0.002. The median OS for patients with no gross disease/microscopically negative was 51.5 months, no gross disease/microscopically positive was 42.6 months and for gross disease was 34.9 months, p=0.018. Conclusion Although as previously reported SCS did not change PFS or OS, for those who underwent the procedure, their operative and pathologic findings were predictive of PFS and OS. Surgical/pathological residual disease is a biomarker of response to chemotherapy and predictive of PFS and OS.
  • Thumbnail Image
    Item
    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.
  • Thumbnail Image
    Item
    Preoperative and pre-chemotherapy CA-125 levels in high-risk early-stage ovarian cancer - An NRG/GOG study
    (Elsevier, 2024) Chan, John K.; Tian, Chunqiao; Kesterson, Joshua P.; Lin, Ken Y.; Darcy, Kathleen; Richardson, Michael T.; Kapp, Daniel S.; Monk, Bradley J.; McNally, Leah; Landrum, Lisa; Copeland, Larry; Walker, Joan L.; Wenham, Robert M.; Phippen, Neil; Spirtos, Nick M.; Tewari, Krishnansu; Shahin, Mark; Berry, Laurel; Bell, Jeffery G.; Obstetrics and Gynecology, School of Medicine
    Objectives: To determine clinical significance of preoperative and pre-chemotherapy CA-125 in high-risk early-stage epithelial ovarian cancer patients. Methods: All patients with stage IA/IB and grade 3, stage IC, clear cell, or completed resected stage II cancer were enrolled in a phase III trial and treated with chemotherapy. Kaplan-Meier method and Cox proportional hazards model were used for statistical analyses. Results: 427 patients with high-risk early-stage ovarian cancer were enrolled. Of 213 patients with preoperative CA-125 data, 79% had elevated CA-125. Median preoperative CA-125 level was 103 U/mL. Patients with ≤10, 11-15, and > 15 cm tumors had median preoperative CA-125 levels of 62, 131 and 158 U/mL, respectively (p = 0.002). For the 350 patients with data for pre-chemotherapy CA-125 level, 69% had elevated pre-chemotherapy CA-125 above 35 U/mL with median value of 65 U/mL. However, age, race, stage, cell type and grade of disease were not correlated with CA-125 levels before and after surgery. On multivariate analysis, elevated pre-chemotherapy CA-125 independently predicted worse recurrence-free survival (HR = 2.13, 95% CI: 1.23-3.69; p = 0.007) and overall survival (HR = 1.99, 95% CI: 1.10-3.59; p = 0.022) after adjusting for age, stage, cell type and grade of disease. Compared to those with normal CA-125, patients with elevated pre-chemotherapy CA-125 had lower recurrence-free survival (RFS, 87% vs. 75%; p = 0.007) and overall survival (OS, 88% vs. 82%; p = 0.02). However, preoperative CA-125 was not prognostic of RFS (p = 0.699) or OS (p = 0.701). Conclusions: Preoperative CA-125 was elevated in nearly 80% of high-risk early-stage ovarian cancer patients. Pre-chemotherapy CA-125 was associated with recurrence-free and overall survival; however, preoperative CA-125 was not prognostic.
  • Thumbnail Image
    Item
    Symptoms of Women With High-Risk, Early-Stage Ovarian Cancer
    (Wolters Kluwer, 2022) Chan, John K.; Tian, Chunqiao; Kesterson, Joshua P.; Monk, Bradley J.; Kapp, Daniel S.; Davidson, Brittany; Robertson, Sharon; Copeland, Larry J.; Walker, Joan L.; Wenham, Robert M.; Casablanca, Yovanni; Spirtos, Nick M.; Tewari, Krishnansu S.; Bell, Jeffery G.; Obstetrics and Gynecology, School of Medicine
    Objective: To assess the presentation, characteristics, and prognostic significance of symptoms in patients with high-risk early-stage epithelial ovarian cancer. Methods: A retrospective chart review was performed on all patients enrolled in a phase III clinical trial (GOG 157). All patients had surgically staged, high-risk early-stage epithelial ovarian cancer (stage IA-IB and grade 3, any clear cell, stage IC or II). Chi-square and Kaplan-Meier estimates and Cox proportional hazards models were used for statistical analyses. Results: Of 419 patients evaluated for symptoms, 301 (72%) presented with one or more symptoms, and 118 (28%) were asymptomatic but had a mass found on examination. Forty percent had only one symptom, and 32% had more than one symptom. Among those with at least one symptom, the most common were abdominal and pelvic pain (31%), and increased girth or fullness (26%). Overall, 23% of patients with tumors 10 cm or smaller, 27% of patients with tumors larger than 10 cm to 15 cm, and 46% of patients with tumors larger than 15 cm had multiple symptoms (P<.001). There was no significant difference in presentation of symptoms based on age, stage, or histologic subtype. Symptoms at diagnosis were not associated with recurrence or survival. Conclusion: More than 70% of patients with high-risk early-stage, epithelial ovarian cancer present with one or more symptoms, with the most common being abdominal or pelvic pain. The proportion of women with symptoms and the number of symptoms increase with enlarging tumor size.