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Tumor grade is a significant determinant of survival in stage two endometrial cancer
Abstracts / Gynecologic Oncology 116 (2010) 593–598
between the two groups for any of the other factors studied, including FIGO stage, grade and survival. Conclusions. In this study, family history of cancer in patients <45 years with EC was associated with worse prognosis, emphasizing the need for aggressive treatment and close monitoring in these patients, and possibly individualized therapeutic regimens based on molecular profiling.
doi:10.1016/j.ygyno.2009.10.013
Tumor grade is a significant determinant of survival in stage two endometrial cancer S. Mourton, G. Xing, W. Fowler, G. Leiserowitz University of California at Davis, Obstetrics and Gynecology Objectives. To determine factors associated with improved survival in patients with stage 2 endometrial adenocarcinoma. Study methods. Using two linked California population databases we identified patients with cervical involvement of endometrial carcinoma. We excluded non-epithelial tumors, clear cell and papillary serous carcinomas. Results. From 1994 to 2001, 1792 patients were identified: 180 patients had involved lymph nodes or distant spread, and 1612 patients had node negative disease and form our study group. The median age was 66 years; 68% underwent simple hysterectomy (SH), 24% underwent radical hysterectomy (RH), and 6% had no surgical management. Just over half of all patients had lymph node sampling, 24% were managed by a gynecologic oncologist, and frequency of adjuvant radiation was similar between SH and RH (49% vs. 43%). Factors associated with decreased survival included; advanced age (HR 1.05, 95% CI 1.04–1.06, p < 0.0001), tumor size (> 2 cm: HR 3.13, 95%CI 1.28–7.69, p = 0.01), tumor grade (Grade> 1: HR 2.33, 95% CI 1.64–3.33, p < 0.0001), and unknown lymph node status (HR 2.19, 95% CI 1.18–4.07, p = 0.01). The use of RT, hysterectomy type, and management by a gynecologic oncologist were not associated with improved survival. Analyzing by hysterectomy type, age and tumor grade continued to be significantly associated with survival. Five-year OS was 74%, 77% for SH, and 80% for RH. Grade 1 tumors had a 5-year OS of 84% compared with 69% for grade > 1. Conclusions. Hysterectomy type and adjuvant radiation do not significantly affect survival. Tumor grade appears to be the most significant determinant of overall survival and should be considered when planning adjuvant therapy.
doi:10.1016/j.ygyno.2009.10.014
Before and after GOG 99: Did our practice patterns for treatment of intermediate risk endometrial adenocarcinoma change? Y. Ioffe, L. Delic, M. Amneus, R. Leuchter, B. Karlan, A. Li, C. Walsh, S. Lentz, R. Farias-Eisner, I. Cass Cedars-Sinai Medical Center, Obstetrics & Gynecology Objectives. To evaluate practice patterns and use of adjuvant radiation therapy in surgically staged intermediate risk endometrial adenocarcinoma patients before and after publication of GOG-99 abstract data. Study methods. Patients diagnosed with stage IB, IC, or II endometrioid endometrial adenocarcinoma were identified under an IRB-approved protocol from three institutions. All patients were diagnosed and surgically staged between 1/1992 and 12/2006. Highintermediate risk (HIR) subgroup was identified according to GOG-99
595
criteria; the remainder of the patients were classified as lowintermediate risk (LIR). Differences in treatment patterns were analyzed “before” and “after” year 2000 to allow for a period of transition to new practice patterns after presentation of GOG-99 abstract data. Results. Among 276 qualifying patients, the median age was 65 (range 29–90). After 2000, fewer LIR patients (50% vs. 27%, p = 0.04) received adjuvant radiation, but the majority (55%) were still treated with external beam radiation (EBRT) ± vaginal brachytherapy (VB). Treatment pattern for HIR subgroup did not change: 53% vs. 56% received radiation before and after 2000, respectively (p = 1.0). After 2000, the majority of HIR patients were still treated with EBRT ± VB (76%). Before 2000, EBRT ± VB vs. VB only were utilized at similar rates within HIR and LIR subgroups (p = 0.3). After 2000, VB was used more frequently for LIR patients and EBRT ± VB was used more frequently for HIR patients (p = 0.04). Conclusions. Following the release of GOG-99 data, practice patterns were altered. In LIR patients, use of adjuvant treatment decreased with a shift toward vaginal brachytherapy only utilization.
doi:10.1016/j.ygyno.2009.10.015
Endometrial carcinoma in-vitro chemosensitivity testing of single and combination chemotherapy regimens using the novel microculture kinetic (MICK) apoptosis assay: Implications for endometrial cancer treatment K. Ballard, H. Homesley, C. Hodson, C. Presant, J. Rutledge, A. Hallquist, M. Perree East Carolina University Brody School of Medicine, Department OB/Gyn, Division of Gynecologic Oncology Objectives. The feasibility of MiCK apoptosis assay to predict single or combination chemotherapy response in endometrial cancer was addressed in a prospective trial. Study methods. Viable endometrial cancer cells from total abdominal hysterectomies were processed in single cell suspensions and plated in individual wells. Single and combination regimens were tested: combinations of doxorubicin, cisplatin, and paclitaxel and carboplatin and paclitaxel [arms for the current Gynecologic Oncology Group (GOG) endometrial cancer phase III trial GOG 209] as well as single agents including paclitaxel, carboplatin, doxorubicin, cisplatin, ifosfamide, and vincristine [all active agents in GOG trials]. Apoptosis was measured continuously over 48 h. Results. Fifteen of nineteen patients had successful assays. The highest mean chemosensitivity was noted in the triple combination of cisplatin, doxorubicin, and paclitaxel with lower mean chemosensitivity for carboplatin and paclitaxel. Combination chemotherapy had higher chemosensitivity than single drug chemotherapy. However, in 25% of patients a single drug had higher chemosensitivity than the combination chemotherapy. As single agents, ifosfamide, cisplatin, and paclitaxel had the highest kinetic unit values. Conclusions. Using simulated clinical dose regimens, the MiCK assay was successful in evaluating in vitro chemosensitivity of endometrial cancer. Results correlated well with GOG clinical trial results. The MiCK assay confirms that most patients are best treated with combination chemotherapy. However, 25% of patients might be best treated with single agent chemotherapy selected by MiCK. MiCK may be useful in future new drug testing and individualizing endometrial cancer patient's chemotherapy management. doi:10.1016/j.ygyno.2009.10.017
between the two groups for any of the other factors studied, including FIGO stage, grade and survival. Conclusions. In this study, family history of cancer in patients <45 years with EC was associated with worse prognosis, emphasizing the need for aggressive treatment and close monitoring in these patients, and possibly individualized therapeutic regimens based on molecular profiling.
doi:10.1016/j.ygyno.2009.10.013
Tumor grade is a significant determinant of survival in stage two endometrial cancer S. Mourton, G. Xing, W. Fowler, G. Leiserowitz University of California at Davis, Obstetrics and Gynecology Objectives. To determine factors associated with improved survival in patients with stage 2 endometrial adenocarcinoma. Study methods. Using two linked California population databases we identified patients with cervical involvement of endometrial carcinoma. We excluded non-epithelial tumors, clear cell and papillary serous carcinomas. Results. From 1994 to 2001, 1792 patients were identified: 180 patients had involved lymph nodes or distant spread, and 1612 patients had node negative disease and form our study group. The median age was 66 years; 68% underwent simple hysterectomy (SH), 24% underwent radical hysterectomy (RH), and 6% had no surgical management. Just over half of all patients had lymph node sampling, 24% were managed by a gynecologic oncologist, and frequency of adjuvant radiation was similar between SH and RH (49% vs. 43%). Factors associated with decreased survival included; advanced age (HR 1.05, 95% CI 1.04–1.06, p < 0.0001), tumor size (> 2 cm: HR 3.13, 95%CI 1.28–7.69, p = 0.01), tumor grade (Grade> 1: HR 2.33, 95% CI 1.64–3.33, p < 0.0001), and unknown lymph node status (HR 2.19, 95% CI 1.18–4.07, p = 0.01). The use of RT, hysterectomy type, and management by a gynecologic oncologist were not associated with improved survival. Analyzing by hysterectomy type, age and tumor grade continued to be significantly associated with survival. Five-year OS was 74%, 77% for SH, and 80% for RH. Grade 1 tumors had a 5-year OS of 84% compared with 69% for grade > 1. Conclusions. Hysterectomy type and adjuvant radiation do not significantly affect survival. Tumor grade appears to be the most significant determinant of overall survival and should be considered when planning adjuvant therapy.
doi:10.1016/j.ygyno.2009.10.014
Before and after GOG 99: Did our practice patterns for treatment of intermediate risk endometrial adenocarcinoma change? Y. Ioffe, L. Delic, M. Amneus, R. Leuchter, B. Karlan, A. Li, C. Walsh, S. Lentz, R. Farias-Eisner, I. Cass Cedars-Sinai Medical Center, Obstetrics & Gynecology Objectives. To evaluate practice patterns and use of adjuvant radiation therapy in surgically staged intermediate risk endometrial adenocarcinoma patients before and after publication of GOG-99 abstract data. Study methods. Patients diagnosed with stage IB, IC, or II endometrioid endometrial adenocarcinoma were identified under an IRB-approved protocol from three institutions. All patients were diagnosed and surgically staged between 1/1992 and 12/2006. Highintermediate risk (HIR) subgroup was identified according to GOG-99
595
criteria; the remainder of the patients were classified as lowintermediate risk (LIR). Differences in treatment patterns were analyzed “before” and “after” year 2000 to allow for a period of transition to new practice patterns after presentation of GOG-99 abstract data. Results. Among 276 qualifying patients, the median age was 65 (range 29–90). After 2000, fewer LIR patients (50% vs. 27%, p = 0.04) received adjuvant radiation, but the majority (55%) were still treated with external beam radiation (EBRT) ± vaginal brachytherapy (VB). Treatment pattern for HIR subgroup did not change: 53% vs. 56% received radiation before and after 2000, respectively (p = 1.0). After 2000, the majority of HIR patients were still treated with EBRT ± VB (76%). Before 2000, EBRT ± VB vs. VB only were utilized at similar rates within HIR and LIR subgroups (p = 0.3). After 2000, VB was used more frequently for LIR patients and EBRT ± VB was used more frequently for HIR patients (p = 0.04). Conclusions. Following the release of GOG-99 data, practice patterns were altered. In LIR patients, use of adjuvant treatment decreased with a shift toward vaginal brachytherapy only utilization.
doi:10.1016/j.ygyno.2009.10.015
Endometrial carcinoma in-vitro chemosensitivity testing of single and combination chemotherapy regimens using the novel microculture kinetic (MICK) apoptosis assay: Implications for endometrial cancer treatment K. Ballard, H. Homesley, C. Hodson, C. Presant, J. Rutledge, A. Hallquist, M. Perree East Carolina University Brody School of Medicine, Department OB/Gyn, Division of Gynecologic Oncology Objectives. The feasibility of MiCK apoptosis assay to predict single or combination chemotherapy response in endometrial cancer was addressed in a prospective trial. Study methods. Viable endometrial cancer cells from total abdominal hysterectomies were processed in single cell suspensions and plated in individual wells. Single and combination regimens were tested: combinations of doxorubicin, cisplatin, and paclitaxel and carboplatin and paclitaxel [arms for the current Gynecologic Oncology Group (GOG) endometrial cancer phase III trial GOG 209] as well as single agents including paclitaxel, carboplatin, doxorubicin, cisplatin, ifosfamide, and vincristine [all active agents in GOG trials]. Apoptosis was measured continuously over 48 h. Results. Fifteen of nineteen patients had successful assays. The highest mean chemosensitivity was noted in the triple combination of cisplatin, doxorubicin, and paclitaxel with lower mean chemosensitivity for carboplatin and paclitaxel. Combination chemotherapy had higher chemosensitivity than single drug chemotherapy. However, in 25% of patients a single drug had higher chemosensitivity than the combination chemotherapy. As single agents, ifosfamide, cisplatin, and paclitaxel had the highest kinetic unit values. Conclusions. Using simulated clinical dose regimens, the MiCK assay was successful in evaluating in vitro chemosensitivity of endometrial cancer. Results correlated well with GOG clinical trial results. The MiCK assay confirms that most patients are best treated with combination chemotherapy. However, 25% of patients might be best treated with single agent chemotherapy selected by MiCK. MiCK may be useful in future new drug testing and individualizing endometrial cancer patient's chemotherapy management. doi:10.1016/j.ygyno.2009.10.017