- Email: [email protected]
Is preoperative routine imaging useful for decision making in early stage cervical cancer?
Abstracts / Gynecologic Oncology 125 (2012) S3–S167
Objective: To evaluate the long-term outcomes and risk factors for recurrence after laparoscopic radical trachelectomy (LRT) in young women with early stage cervical cancer. Methods: All consecutive patients with early stage cervical cancer who tried LRT were included from 3 tertiary cancer specializing centers in Korea. Of 71 patients who tried LRT, 9 patients were converted to LRH followed by adjuvant concurrent chemoradiation therapy because intraoperative frozen biopsy revealed lymph node metastasis or parametrial invasion. Outcomes were analyzed on the 62 patients who completed LRT. Results: The mean age and mean tumor size were 30 years (range, 20–44 years) and 2.1 cm (range, 0.4-6 cm), respectively. Twenty five patients had tumor larger than 2 cm and 6 of them received neoadjuvant chemotherapy with 3 cycles of paclitaxel and carboplatin before LRT. FIGO stage was IA1 in 4 patients, IA2 in 2, IB1 in 52, IB2 in 1, IIA1 in 2, and IIB in 1. Histologic type of tumor was squamous cell carcinoma in 54 patients and adeno- or adenosquamous carcionoma in 8 patients. Histologic grade of tumor was 1 in 11 patients, 2 in 39 patients, and 3 in 12 patients. Pathology report after LRT revealed lymphovascular space invasion in 8 patients and cervical stromal invasion N 50% in 15 patients. After median follow-up time of 38 months (range, 3–86 months), 7 patients had recurrence and 1 patient died of disease. 5-year disease-free survival (DFS) and overall survival (OS) rates were 88% and 97%, respectively. The 5-year DFS were significantly higher in patients with tumor b 2 cm (94% vs. 79%, P=0.041) and cervical stromal invasion b 50% (93% vs. 67%, P=0.0174). However, age, histology, tumor grade, lymphovascular space invasion were not associated with DFS. Conclusions: Survival outcomes after LRT in young women with early stage cervical cancer were excellent. However, because tumor N 2 cm and cervical stromal invasion N 50% were associated with higher risk of recurrence, adjuvant therapy such as chemotherapy is recommended.
S63
cases showed pelvic metastasis such as pelvic side wall invasion, peritoneal seeding with or without paraaortic lymph node metastasis. Ten patients attempted to conceive, and four succeeded. Conclusions: Indications of LRT should be strict to universal criteria. Our study showed a higher tendency to recurrence in those whose tumor size is larger than 2cm. Recurrence rate of patients who recceived neoadjuvant chemotherapy showed higher recurrence rate (1/5) than tumor less than 3cm. More generous use of adjuvant chemotherapy might be recommended in LRT.
doi:10.1016/j.ygyno.2011.12.149
149 Long-term survival outcomes of laparoscopic radical trachelectomy in early cervical cancer: A single institute experience D. Kim, Y. Koo, J. Park, J. Kim, Y. Kim, Y. Kim, J. Nam. Asan Medical Center, Seoul, Republic of Korea. Objective: To evaluate the outcomes of laparoscopic radical trachelectomy (LRT) focusing on the recurrence rate of cervical cancer and to address the possible factors associated with tumor recurrence. Methods: Between 2004 and 2011, we tried LRT in fifty-five consecutive patients who desired to preserve fertility in early stage cervical cancer in Asan Medical Center. In seven patients, the planned LRT procedures were abandoned during the operations because of lymph node metastasis, close resection margin or parametrial involvement on frozen section. Forty seven patients were eligible for this analysis. Retrospective chart review was conducted. Results: Mean tumor size was 1.98 (range, 0.4-6) cm and operative time was 5.2 (range, 2–8.5) hours. There were one patient in FIGO stage IA1, 43 (91.5%) in stage IB, two in stage IIA and one in IIB. Median number of pelvic and paraaortic lymph node retrieved were 24.6 (range, 9–51) and 1.3 (range, 0–7), respectively. After a median follow-up time of 38 months (range, 3–87 months), there were five recurrences and one death of disease. Median time from surgery to recurrence was 7 (range, 8–20) months. Three-year disease free survival rate of all 47 patients was 86.9% but in patients with tumor size less than 2cm, 3YDFSR was 92.1% (p=0.054) (Fig. 1). Five patients with large tumors (N3cm) who were given neoadjuvant chemotherapy showed 20% recurrence rate (1/5). All of recurred
doi:10.1016/j.ygyno.2011.12.150
150 Is preoperative routine imaging useful for decision making in early stage cervical cancer? L. Gien1, M. Bernardini2, R. Kupets1, S. Mitra3, A. Covens1. 1Sunnybrook Odette Cancer Center, Toronto, Canada, 2Princess Margaret Hospital, Toronto, Canada, 3University of Toronto, Toronto, Canada. Objective: To determine circumstances where preoperative CT or MRI would be most useful to direct management in early stage cervical cancer. Methods: Data was collected on all cases of early stage cervix cancer between January 1, 2005 and June 30, 2010 at two tertiary care cancer centers. Inclusion criteria were ages 18–75, clinical tumor size b4 cm, and a plan of possible surgery after clinical assessment. The cohort was analyzed to determine characteristics where MRI and/or CT had a role in changing management. In the surgical group, clinical exam and imaging were compared to final pathology results. Statistical analysis included Student t-test for continuous data and chi-square test for categorical data. Results: After clinical assessment, 352 patients were being considered for primary surgery for early stage cervix cancer, FIGO stage 1B1 or less.
S64
Abstracts / Gynecologic Oncology 125 (2012) S3–S167
Mean age was 45 years, 74% had no comorbidities, and 55% had squamous histology. Two hundred and ninety-eight women had surgery as their definitive management, with 80% radical hysterectomy, 18% radical trachelectomy. One hundred and seventy-two patients (49%) had a preoperative MRI or CT or both. After clinical exam, 283 (80%) had a plan for surgery, while 69 (20%) were still undetermined; after imaging, 18 patients (5%) initially planned for surgery changed to primary chemoradiation, while the 69 undetermined were split between surgery (9%) and chemoradiation (10%). Characteristics where imaging influenced management were tumors N2 cm (p b 0.0001), visible lesions (p b 0.0001), and suspicious findings on pelvirectal examination such as nodularity, tethering, or possible parametrial involvement (p b 0.0001). Among the 265 patients whose plan for surgery remained unchanged, 85 (32%) had preoperative imaging which did not affect clinical management. Among those with surgery, clinical palpation was more accurate than MRI in determining size of tumor within 0.5 cm (62% vs 52%). MRI had a sensitivity of only 35% in detecting outer cervical invasion, 14% false negative rate for lymph node involvement, and 6% false negative rate for parametrial disease, which was no different than false negative rates by clinical exam (11%, p = 0.49 and 2%, p = 0.18 respectively). Conclusions: MRI and CT scans should not be ordered routinely for all early stage cervix cancers, as only a limited number have a change in management based on the test results. Preoperative imaging is most useful for those with tumors N2 cm, visible lesions, and suspicious findings on clinical exam.
doi:10.1016/j.ygyno.2011.12.151
151 The expression of antiapoptotic protein API5 in cervical neoplasias H. Cho1, J. Chung2, S. Kim1, D. Chay1, S. Hewitt2, J. Kim1. 1Yonsei University College of Medicine, Seoul, Republic of Korea, 2National Cancer Institute, Bethesda, MD. Objective: It has been shown in various tumors that dysregulation of apoptosis was closely correlated with carcinogenesis and malignant phenotype of tumor cells. The apoptosis inhibitor-5 [API5, also called antiapoptosis clone 11 (AAC11)] is a poorly studied nuclear protein whose expression has been shown to prevent apoptosis after deprivation of growth factor. This study explored expression of API5 and its relationship with the clinicopathological factors and survival in cervical neoplasias. Methods: Four hundred fifty-nine cervical tumor samples and matched normal epithelial samples were arrayed into tissue microarrays. The expression of API5 was studied using immunohistochemical analysis. The correlation between API5 expression and overall and disease-free survival was analyzed using both univariate and multivariate analyses adjusting for the known prognostic factors. Results: Expressions of API5 was significantly increased in cervical cancer cases compared with normal epitheliums (P b 0.001). Increased API5 expression was observed in patients with increasing tumor grade (P b 0.001) and platinum resistant group. In multivariate analysis, API5 positivity was an independent prognostic factor for disease-free survival (HR = 2.97 [1.24-7.09], P = 0.014) and overall survival (HR = 3.56 [1.22-10.44], P = 0.020). Conclusions: This study provides evidence for an association between API5 expression and cervical neoplasias and shows that API5 expression predicts poor prognosis in cervical cancer. Our findings also suggest that future research assessing its clinical usefulness would be worthwhile. doi:10.1016/j.ygyno.2011.12.152
152 A re-evaluation of contemporary risk models for early stage cervical cancer C. Mathews1, S. Lee2, E. Nugent1, L. Landrum1, E. Bishop1, Y. Kim2, J. Nam2, Y. Kim2, D. McMeekin1. 1The University of Oklahoma Health Sciences Center, Oklahoma City, OK, 2University of Ulsan, Asan Medical Center, Republic of Korea. Objective: Surgical-pathologic studies in early stage cervical cancer are responsible for the development of currently-used risk models. We sought to investigate which factors are associated with risk of recurrence, and to compare the outcomes of patients stratified by risk models. Methods: A two institution, multi-national database of 664 patients with stage I cervical cancer was created from retrospective review of charts between 1998 and 2010. All patients underwent radical hysterectomy (RH) and pelvic +/− para-aortic lymphadenectomy. Surgical-pathologic variables (including grade, depth of cervical invasion, lymphovascular space invasion, histology, and nodal status) were evaluated. Patients were categorized into risk groups based on criteria used in GOG 109 (high risk [HR]) and GOG 92 (intermediate risk [IR]). Low risk patients were defined by characteristics less than intermediate risk. Post-operative treatment was tailored by individual physician. Outcomes evaluated included nodal positivity rates, recurrence rates, and PFS. Results: Six hundred and sixty-four patients meeting eligibility criteria were identified with a median follow up of 25 months. The median age was 46 years, 63% had squamous histology, and 34% had adenocarcinoma. The stage distribution of all patients included: 4% IA2, 79% IB1, 14% IB2. With a median of 28 pelvic nodes and 2 paraaortic nodes removed, 16% of patients had (+) nodal disease. By risk models, 365(59%) were classified as low risk, and the recurrence rate was 5% among these patients with a 3-yr PFS of 95%. Of these pts only 5% received post op radiation. Pts classified into IR were divided into 4 groups used in GOG 92: Among the HR group (n= 134), 20% recurred versus 23% in the IR group. The 3-yr PFS was 80% and 77% in HR and IR subjects respectively. 86% of HR patients received chemoXRT. In a multivariate analysis, only cervical depth of invasion was a predictive variable. Conclusions: Of patients with cervical cancer undergoing RH, 41% meet criteria for elevated risk. IR models are complex and may not reflect outcomes, either due to disease characteristics or treatment differences. The more common use of chemo-XRT appears to reduce the risk of HR patients to that of IR.
N
LVSI
Depth
Size
PFS @ 3 yr (%)
Chemo-XRT (%)
49 17 3 36
+ + + (−)
Deep 1/3 Mid 1/3 Superficial 1/3 N mid 1/3
Any cm ≥ 2 cm ≥ 5 cm ≥ 4 cm
78% 65% 66% 79%
67% 40% 100% 20%
doi:10.1016/j.ygyno.2011.12.153
153 Outcome of patients with FIGO stage IB2 treated with radical hysterectomy before and after the era of adjuvant chemoradiation for high and intermediate risk factors: 20 years of a single-institution experience N. McKenzie1, M. Pasternak1, J. Diaz1, D. English1, N. Lambrou2, J. Pearson1, D. Wrenn1, S. Schuman1, F. Simpkins1, J. Lucci1. 1University of Miami Sylvester Cancer Center, Miami, FL, 2Baptist Health System, Miami, FL.
Objective: To evaluate the long-term outcomes and risk factors for recurrence after laparoscopic radical trachelectomy (LRT) in young women with early stage cervical cancer. Methods: All consecutive patients with early stage cervical cancer who tried LRT were included from 3 tertiary cancer specializing centers in Korea. Of 71 patients who tried LRT, 9 patients were converted to LRH followed by adjuvant concurrent chemoradiation therapy because intraoperative frozen biopsy revealed lymph node metastasis or parametrial invasion. Outcomes were analyzed on the 62 patients who completed LRT. Results: The mean age and mean tumor size were 30 years (range, 20–44 years) and 2.1 cm (range, 0.4-6 cm), respectively. Twenty five patients had tumor larger than 2 cm and 6 of them received neoadjuvant chemotherapy with 3 cycles of paclitaxel and carboplatin before LRT. FIGO stage was IA1 in 4 patients, IA2 in 2, IB1 in 52, IB2 in 1, IIA1 in 2, and IIB in 1. Histologic type of tumor was squamous cell carcinoma in 54 patients and adeno- or adenosquamous carcionoma in 8 patients. Histologic grade of tumor was 1 in 11 patients, 2 in 39 patients, and 3 in 12 patients. Pathology report after LRT revealed lymphovascular space invasion in 8 patients and cervical stromal invasion N 50% in 15 patients. After median follow-up time of 38 months (range, 3–86 months), 7 patients had recurrence and 1 patient died of disease. 5-year disease-free survival (DFS) and overall survival (OS) rates were 88% and 97%, respectively. The 5-year DFS were significantly higher in patients with tumor b 2 cm (94% vs. 79%, P=0.041) and cervical stromal invasion b 50% (93% vs. 67%, P=0.0174). However, age, histology, tumor grade, lymphovascular space invasion were not associated with DFS. Conclusions: Survival outcomes after LRT in young women with early stage cervical cancer were excellent. However, because tumor N 2 cm and cervical stromal invasion N 50% were associated with higher risk of recurrence, adjuvant therapy such as chemotherapy is recommended.
S63
cases showed pelvic metastasis such as pelvic side wall invasion, peritoneal seeding with or without paraaortic lymph node metastasis. Ten patients attempted to conceive, and four succeeded. Conclusions: Indications of LRT should be strict to universal criteria. Our study showed a higher tendency to recurrence in those whose tumor size is larger than 2cm. Recurrence rate of patients who recceived neoadjuvant chemotherapy showed higher recurrence rate (1/5) than tumor less than 3cm. More generous use of adjuvant chemotherapy might be recommended in LRT.
doi:10.1016/j.ygyno.2011.12.149
149 Long-term survival outcomes of laparoscopic radical trachelectomy in early cervical cancer: A single institute experience D. Kim, Y. Koo, J. Park, J. Kim, Y. Kim, Y. Kim, J. Nam. Asan Medical Center, Seoul, Republic of Korea. Objective: To evaluate the outcomes of laparoscopic radical trachelectomy (LRT) focusing on the recurrence rate of cervical cancer and to address the possible factors associated with tumor recurrence. Methods: Between 2004 and 2011, we tried LRT in fifty-five consecutive patients who desired to preserve fertility in early stage cervical cancer in Asan Medical Center. In seven patients, the planned LRT procedures were abandoned during the operations because of lymph node metastasis, close resection margin or parametrial involvement on frozen section. Forty seven patients were eligible for this analysis. Retrospective chart review was conducted. Results: Mean tumor size was 1.98 (range, 0.4-6) cm and operative time was 5.2 (range, 2–8.5) hours. There were one patient in FIGO stage IA1, 43 (91.5%) in stage IB, two in stage IIA and one in IIB. Median number of pelvic and paraaortic lymph node retrieved were 24.6 (range, 9–51) and 1.3 (range, 0–7), respectively. After a median follow-up time of 38 months (range, 3–87 months), there were five recurrences and one death of disease. Median time from surgery to recurrence was 7 (range, 8–20) months. Three-year disease free survival rate of all 47 patients was 86.9% but in patients with tumor size less than 2cm, 3YDFSR was 92.1% (p=0.054) (Fig. 1). Five patients with large tumors (N3cm) who were given neoadjuvant chemotherapy showed 20% recurrence rate (1/5). All of recurred
doi:10.1016/j.ygyno.2011.12.150
150 Is preoperative routine imaging useful for decision making in early stage cervical cancer? L. Gien1, M. Bernardini2, R. Kupets1, S. Mitra3, A. Covens1. 1Sunnybrook Odette Cancer Center, Toronto, Canada, 2Princess Margaret Hospital, Toronto, Canada, 3University of Toronto, Toronto, Canada. Objective: To determine circumstances where preoperative CT or MRI would be most useful to direct management in early stage cervical cancer. Methods: Data was collected on all cases of early stage cervix cancer between January 1, 2005 and June 30, 2010 at two tertiary care cancer centers. Inclusion criteria were ages 18–75, clinical tumor size b4 cm, and a plan of possible surgery after clinical assessment. The cohort was analyzed to determine characteristics where MRI and/or CT had a role in changing management. In the surgical group, clinical exam and imaging were compared to final pathology results. Statistical analysis included Student t-test for continuous data and chi-square test for categorical data. Results: After clinical assessment, 352 patients were being considered for primary surgery for early stage cervix cancer, FIGO stage 1B1 or less.
S64
Abstracts / Gynecologic Oncology 125 (2012) S3–S167
Mean age was 45 years, 74% had no comorbidities, and 55% had squamous histology. Two hundred and ninety-eight women had surgery as their definitive management, with 80% radical hysterectomy, 18% radical trachelectomy. One hundred and seventy-two patients (49%) had a preoperative MRI or CT or both. After clinical exam, 283 (80%) had a plan for surgery, while 69 (20%) were still undetermined; after imaging, 18 patients (5%) initially planned for surgery changed to primary chemoradiation, while the 69 undetermined were split between surgery (9%) and chemoradiation (10%). Characteristics where imaging influenced management were tumors N2 cm (p b 0.0001), visible lesions (p b 0.0001), and suspicious findings on pelvirectal examination such as nodularity, tethering, or possible parametrial involvement (p b 0.0001). Among the 265 patients whose plan for surgery remained unchanged, 85 (32%) had preoperative imaging which did not affect clinical management. Among those with surgery, clinical palpation was more accurate than MRI in determining size of tumor within 0.5 cm (62% vs 52%). MRI had a sensitivity of only 35% in detecting outer cervical invasion, 14% false negative rate for lymph node involvement, and 6% false negative rate for parametrial disease, which was no different than false negative rates by clinical exam (11%, p = 0.49 and 2%, p = 0.18 respectively). Conclusions: MRI and CT scans should not be ordered routinely for all early stage cervix cancers, as only a limited number have a change in management based on the test results. Preoperative imaging is most useful for those with tumors N2 cm, visible lesions, and suspicious findings on clinical exam.
doi:10.1016/j.ygyno.2011.12.151
151 The expression of antiapoptotic protein API5 in cervical neoplasias H. Cho1, J. Chung2, S. Kim1, D. Chay1, S. Hewitt2, J. Kim1. 1Yonsei University College of Medicine, Seoul, Republic of Korea, 2National Cancer Institute, Bethesda, MD. Objective: It has been shown in various tumors that dysregulation of apoptosis was closely correlated with carcinogenesis and malignant phenotype of tumor cells. The apoptosis inhibitor-5 [API5, also called antiapoptosis clone 11 (AAC11)] is a poorly studied nuclear protein whose expression has been shown to prevent apoptosis after deprivation of growth factor. This study explored expression of API5 and its relationship with the clinicopathological factors and survival in cervical neoplasias. Methods: Four hundred fifty-nine cervical tumor samples and matched normal epithelial samples were arrayed into tissue microarrays. The expression of API5 was studied using immunohistochemical analysis. The correlation between API5 expression and overall and disease-free survival was analyzed using both univariate and multivariate analyses adjusting for the known prognostic factors. Results: Expressions of API5 was significantly increased in cervical cancer cases compared with normal epitheliums (P b 0.001). Increased API5 expression was observed in patients with increasing tumor grade (P b 0.001) and platinum resistant group. In multivariate analysis, API5 positivity was an independent prognostic factor for disease-free survival (HR = 2.97 [1.24-7.09], P = 0.014) and overall survival (HR = 3.56 [1.22-10.44], P = 0.020). Conclusions: This study provides evidence for an association between API5 expression and cervical neoplasias and shows that API5 expression predicts poor prognosis in cervical cancer. Our findings also suggest that future research assessing its clinical usefulness would be worthwhile. doi:10.1016/j.ygyno.2011.12.152
152 A re-evaluation of contemporary risk models for early stage cervical cancer C. Mathews1, S. Lee2, E. Nugent1, L. Landrum1, E. Bishop1, Y. Kim2, J. Nam2, Y. Kim2, D. McMeekin1. 1The University of Oklahoma Health Sciences Center, Oklahoma City, OK, 2University of Ulsan, Asan Medical Center, Republic of Korea. Objective: Surgical-pathologic studies in early stage cervical cancer are responsible for the development of currently-used risk models. We sought to investigate which factors are associated with risk of recurrence, and to compare the outcomes of patients stratified by risk models. Methods: A two institution, multi-national database of 664 patients with stage I cervical cancer was created from retrospective review of charts between 1998 and 2010. All patients underwent radical hysterectomy (RH) and pelvic +/− para-aortic lymphadenectomy. Surgical-pathologic variables (including grade, depth of cervical invasion, lymphovascular space invasion, histology, and nodal status) were evaluated. Patients were categorized into risk groups based on criteria used in GOG 109 (high risk [HR]) and GOG 92 (intermediate risk [IR]). Low risk patients were defined by characteristics less than intermediate risk. Post-operative treatment was tailored by individual physician. Outcomes evaluated included nodal positivity rates, recurrence rates, and PFS. Results: Six hundred and sixty-four patients meeting eligibility criteria were identified with a median follow up of 25 months. The median age was 46 years, 63% had squamous histology, and 34% had adenocarcinoma. The stage distribution of all patients included: 4% IA2, 79% IB1, 14% IB2. With a median of 28 pelvic nodes and 2 paraaortic nodes removed, 16% of patients had (+) nodal disease. By risk models, 365(59%) were classified as low risk, and the recurrence rate was 5% among these patients with a 3-yr PFS of 95%. Of these pts only 5% received post op radiation. Pts classified into IR were divided into 4 groups used in GOG 92: Among the HR group (n= 134), 20% recurred versus 23% in the IR group. The 3-yr PFS was 80% and 77% in HR and IR subjects respectively. 86% of HR patients received chemoXRT. In a multivariate analysis, only cervical depth of invasion was a predictive variable. Conclusions: Of patients with cervical cancer undergoing RH, 41% meet criteria for elevated risk. IR models are complex and may not reflect outcomes, either due to disease characteristics or treatment differences. The more common use of chemo-XRT appears to reduce the risk of HR patients to that of IR.
N
LVSI
Depth
Size
PFS @ 3 yr (%)
Chemo-XRT (%)
49 17 3 36
+ + + (−)
Deep 1/3 Mid 1/3 Superficial 1/3 N mid 1/3
Any cm ≥ 2 cm ≥ 5 cm ≥ 4 cm
78% 65% 66% 79%
67% 40% 100% 20%
doi:10.1016/j.ygyno.2011.12.153
153 Outcome of patients with FIGO stage IB2 treated with radical hysterectomy before and after the era of adjuvant chemoradiation for high and intermediate risk factors: 20 years of a single-institution experience N. McKenzie1, M. Pasternak1, J. Diaz1, D. English1, N. Lambrou2, J. Pearson1, D. Wrenn1, S. Schuman1, F. Simpkins1, J. Lucci1. 1University of Miami Sylvester Cancer Center, Miami, FL, 2Baptist Health System, Miami, FL.