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A new suggested pattern-based clinical classification system for endocervical adenocarcinoma
62
Abstracts / Gynecologic Oncology 133 (2014) 2–207
Conclusions: Special consideration of the significance of multiple high-risk factors merits further investigation in the management of surgically treated early-stage cervical cancer.
doi:10.1016/j.ygyno.2014.03.168
149 — Poster Session A Cervical adenocarcinoma in situ with coexisting squamous cell lesions: Impact on recurrence T. Song1, B.S. Yoon1, Y.Y. Lee2, C.H. Choi2, T.J. Kim3, J.W. Lee3, D.S. Bae3, B.G. Kim3, M.K. Kim4. 1CHA Gangnam Medical Center, CHA University, Seoul, South Korea, 2Samsung Medical Center, Seoul, South Korea, 3Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea, 4Sung Kyun Kwan University of Medicine, Changwon-Si, South Korea. doi:10.1016/j.ygyno.2014.03.167
148 - Poster Session A The impact of multiple high-risk factors on survival outcome of surgically treated early-stage cervical cancer K. Matsuo1, S. Mabuchi2, M. Okazawa2, Y. Matsumoto3, K. Yoshino2, S. Kamiura4, Y.G. Lin5, L.D. Roman1, T. Kimura2. 1USC/LAC Medical Center - Women and Children’s Hospital, Los Angeles, CA, USA, 2Osaka University, Suita, Japan, 3Osaka University, Osaka, Japan, 4Osaka Medical Center for Cancer and Cardiovascular Disease, Osaka, Japan, 5University of Southern California, Los Angeles, CA, USA. Objectives: Surgical-pathological risk factors obtained from radical hysterectomy specimen are valuable in the management of earlystage cervical cancer to identify a subset of patients who will benefit from adjuvant therapy. However, the significance of multiple highrisk factors on survival is not well elucidated. Methods: A retrospective study was conducted for surgically treated cervical cancer patients (stage IA2-IIB, n = 540). Surgical-pathological risk factors were examined, and tumors expressing ≥1 high-risk factors (nodal metastasis, parametrial involvement, or positive surgical margin) were eligible for analysis (n = 177 [32.8%]). Survival analysis was performed based on the number of high-risk factors and the type of adjuvant therapy. Results: Among 177 cases, 68 (38.4%) expressed multiple high-risk factors (2 risk factors, n = 58 [32.8%]; 3 risk factors, n = 10 [5.6%]). Five-year progression-free survival (PFS) for 1, 2, and 3 high-risk factors were 71.2%, 50.3%, and 30%, respectively (P b 0.001) and were 78.2%, 62.3%, and 55.9%, respectively, for overall survival (OS) (P = 0.009). Postoperatively, 101 (57.1%) patients received concurrent chemoradiotherapy (CCRT) and 76 (42.9%) received radiotherapy alone (RT). CCRT was beneficial for tumors expressing only a single high-risk factor: hazard ratio (HR) for CCRT over RT alone for PFS and OS were 0.27 (95% CI 0.13–0.57, P = 0.001) and 0.31 (95% CI 0.13– 0.72, P = 0.007), respectively. The benefit of CCRT diminished when tumors expressed multiple high-risk factors: HR for PFS and OS were 0.72 (95% CI 0.37–1.38, P = 0.32) and 0.78 (95% CI 0.36–1.73, P = 0.55), respectively.
Objectives: The aim of this study was to assess the relative incidences of cervical adenocarcinoma in situ (AIS) and squamous cell carcinoma in situ (sCIS) and to determine the impact of coexisting squamous cell lesions on outcomes in patients with cervical AIS. Methods: We performed a retrospective review of patients diagnosed with AIS or sCIS who underwent conization at a university hospital between 2000 and 2011. Results: A total of 1184 patients with cervical carcinoma in situ were included. The ratio of sCIS to AIS was 16:1. Among 71 patients with AIS, AIS with coexisting squamous cell lesions and AIS alone were detected in 41 patients (58%) and 30 patients (42%), respectively. The Papanicolaou smear results before conization in patients with AIS and coexisting squamous cell lesions showed squamous, glandular, and combined cell abnormalities in 93%, 2%, and 2% of patients, respectively, whereas the Papanicolaou smear results of patients with AIS alone showed squamous, glandular, and combined cell abnormalities in 37%, 43%, and 10% of patients, respectively (P b 0.001). During the median follow-up of 57.1 months, five episodes of AIS recurrences and one episode of invasive recurrence occurred. The recurrence rate was significantly higher in patients with AIS alone than in patients with AIS and coexisting squamous cell lesions (17% vs 2%; P = 0.043). Conclusions: Patients with AIS alone on conization sample are more likely to experience recurrence, whereas patients with AIS and coexisting squamous cell lesions may be treated conservatively. doi:10.1016/j.ygyno.2014.03.169
150 — Poster Session A A new suggested pattern-based clinical classification system for endocervical adenocarcinoma N. Thomakos, M. Sotiropoulou, D. Zacharakis, I. Koutroumpa, E. Valla, S.P. Trachana, D. Haidopoulos, F. Zagouri, G. Vlachos, A. Rodolakis. Alexandra Hospital, University of Athens, Athens, Greece. Objectives: According to FIGO classification, endocervical adenocarcinoma (EAC) staging is based on tumor depth of invasion (DOI). Because EAC spreads primarily by lymphatic dissemination, treatment
Abstracts / Gynecologic Oncology 133 (2014) 2–207
of patients with EAC needs to address not only the primary tumor size but also the adjacent tissues and lymph nodes (LNs). The objective of this study was to investigate other pathologic factors that could better identify those patients at risk of developing LN metastases. Methods: A retrospective review of records of patients with EAC treated in our institution. Data regarding clinical and pathologic features, such as DOI, tumor size, lymphovascular invasion (LVI), and pattern of tumor invasion, were defined. Suggesting a newly devised system, the above parameters were categorized as followed: Pattern A: well-confined glands, disregarding DOI; Pattern B: early invasion of stroma, originating from well-confined glands; Pattern C: spread, destructive invasion. Results: A total of 103 women aged 21 to 79 years (mean, 50.67 years) were identified with EAC. All patients were staged between IA2 and IV, with DOI ranging from 3.5 to N40 mm; LVI was documented in 42 cases. To compare the standard staging method using DOI criteria and the suggested new method with patterns, we created the following table:
Standard Method Pattern A Pattern B Pattern C
Patients
Patients with
Total LN
# Pos LN
Stage I
Stage II - IV
103
Pos LN 15 (14.6%)
2281
35 (1.53%)
65 (63.1%)
38 (36.9%)
20 (19.4%) 35 (33.9%) 48 (46.7%)
0 (0%) 4 (11.4%) 11 (22.9%)
451 680 1150
0 (0%) 10 (1.5%) 25 (2.2%)
20 (100%) 25 (71.4%) 20 (41.6%)
0 (0%) 10 (28.6%) 28 (58.3%)
Conclusions: As shown, a percentage of the 19.4% of patients (Pattern A, stage I) would not need LN resection, according to the suggested histologic classification for EAC. Moreover, patients with Pattern B characteristics rarely have LN metastases because 71.4% of them have stage I disease. In contrast, patients with Pattern C should receive aggressive treatment because 22.9% of them have LN involvement. Additionally, most patients who have higher-stage disease have tumors in Pattern C. Therefore, our data suggest that this new pattern-based method of classifying EAC could be clinically significant because it is simple and consistent.
doi:10.1016/j.ygyno.2014.03.170
151 — Poster Session A Differentiation between high- and low-grade cervical intraepithelial neoplasia by p16 immunoexpression C.E.M.D.C. Andrade, M.A. Vieira, R. Dos Reis, A.T. Tsunoda, A. Longatto-Filho, C. Scapulatempo-Neto, I.D.C.G. Da Silva, J.H.T.G. Fregnani. Barretos Cancer Hospital, Barretos, Brazil. Objectives: Inter-rater disagreement may occur when differentiating high-grade from low-grade cervical intraepithelial neoplasia (CIN) in clinical routine. The use of p16 immunohistochemistry could help the pathologist to differentiate these two presentations of CIN. Methods: We performed a retrospective analysis of all consecutive cone specimens from patients who underwent surgical treatment for CIN between July 2009 and February 2011. The pathological results were classified into low-grade CIN and high-grade CIN, and these two groups were compared with p16 immunohistochemistry. p16 was considered positive when 75% of the neoplasia had moderate or strong staining. Categories were compared by means of chi-square test. A P value b0.05 was considered significant. Results: Among 277 women, 20 (7.2%) of cone specimens showed low-grade CIN and 257 (92.8%) showed high-grade CIN. In low-grade CIN histology group, 18 (90%) had negative p16 stain and 2 (10%) had positive p16 stain. In the high-grade CIN group, 72 (28%) had negative p16 stain and 185 (72%) were positive. The difference between the two groups was statistically significant (P b0.0001) (Table 1).
63
Conclusions: The use of p16 immunohistochemistry had the capacity to differentiate high-grade from low-grade CIN, and this tool should be used clinically to reduce inter-rater disagreement. Table 1. Distribution of p16 Staining by CIN Histology. p16 negative
p16 positive
n (%)
n (%)
Low-grade
18 (90%)
2 (10%)
High-grade
72 (28%)
185 (72%)
CIN Histology
P value
<0.0001
doi:10.1016/j.ygyno.2014.03.171
152 — Poster Session A Risk factors for cervical intraepithelial neoplasia (CIN) recurrence in patients with positive cone margins C.E.M.D.C. Andrade1, R. Dos Reis1, M.A. Vieira1, I.D.C.G. Da Silva1, A.T. Tsunoda1, J.H.T.G. Fregnani1, F.A. Soares2. 1Barretos Cancer Hospital, Barretos, Brazil, 2AC Camargo Cancer Center, Sao Paulo, Brazil. Objectives: Positive cone margins are an important factor related to CIN recurrence after conization, but not all women with these findings will have recurrences. We evaluated the risk factors associated with CIN recurrence after surgical treatment in patients with positive cone margins. Methods: Ninety-seven women who underwent surgery between July 2009 and February 2011 due to CIN and who had positive surgical margins at final pathology reports were analyzed. Clinical (age, tobacco consumption, and parity) and pathologic (histopathologic diagnosis and glandular extension) factors and biomarkers (high-risk human papillomavirus (HPV) detection by COBAS test® in the pretreatment cytology and p16 immunoexpression in the surgical specimen) were evaluated by univariate and multivariate analyses to determine the predictors of recurrence in 2 years. Results: The median follow-up was 22.6 months (range, 0.7– 37.5 months). There were 33 recurrences of CIN after treatment (34.0%). The 2-year disease-free survival rate was 66.3% (95% CI 56.3%– 76.3%). After univariate analysis, positive HPV-16, tobacco consumption, and age were considered for multivariate analysis. In multivariate analysis (Table 1), the single independent risk factor for recurrence was tobacco consumption (HR 3.5, 95% CI 1.6–7.6, P = 0.002). Conclusions: Women with tobacco consumption and positive surgical margins at conization had a higher risk of recurrence. Tobacco cessation is strongly recommended in this population. Table 1. Multivariate Analysis (Cox Model).
doi:10.1016/j.ygyno.2014.03.172
Abstracts / Gynecologic Oncology 133 (2014) 2–207
Conclusions: Special consideration of the significance of multiple high-risk factors merits further investigation in the management of surgically treated early-stage cervical cancer.
doi:10.1016/j.ygyno.2014.03.168
149 — Poster Session A Cervical adenocarcinoma in situ with coexisting squamous cell lesions: Impact on recurrence T. Song1, B.S. Yoon1, Y.Y. Lee2, C.H. Choi2, T.J. Kim3, J.W. Lee3, D.S. Bae3, B.G. Kim3, M.K. Kim4. 1CHA Gangnam Medical Center, CHA University, Seoul, South Korea, 2Samsung Medical Center, Seoul, South Korea, 3Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea, 4Sung Kyun Kwan University of Medicine, Changwon-Si, South Korea. doi:10.1016/j.ygyno.2014.03.167
148 - Poster Session A The impact of multiple high-risk factors on survival outcome of surgically treated early-stage cervical cancer K. Matsuo1, S. Mabuchi2, M. Okazawa2, Y. Matsumoto3, K. Yoshino2, S. Kamiura4, Y.G. Lin5, L.D. Roman1, T. Kimura2. 1USC/LAC Medical Center - Women and Children’s Hospital, Los Angeles, CA, USA, 2Osaka University, Suita, Japan, 3Osaka University, Osaka, Japan, 4Osaka Medical Center for Cancer and Cardiovascular Disease, Osaka, Japan, 5University of Southern California, Los Angeles, CA, USA. Objectives: Surgical-pathological risk factors obtained from radical hysterectomy specimen are valuable in the management of earlystage cervical cancer to identify a subset of patients who will benefit from adjuvant therapy. However, the significance of multiple highrisk factors on survival is not well elucidated. Methods: A retrospective study was conducted for surgically treated cervical cancer patients (stage IA2-IIB, n = 540). Surgical-pathological risk factors were examined, and tumors expressing ≥1 high-risk factors (nodal metastasis, parametrial involvement, or positive surgical margin) were eligible for analysis (n = 177 [32.8%]). Survival analysis was performed based on the number of high-risk factors and the type of adjuvant therapy. Results: Among 177 cases, 68 (38.4%) expressed multiple high-risk factors (2 risk factors, n = 58 [32.8%]; 3 risk factors, n = 10 [5.6%]). Five-year progression-free survival (PFS) for 1, 2, and 3 high-risk factors were 71.2%, 50.3%, and 30%, respectively (P b 0.001) and were 78.2%, 62.3%, and 55.9%, respectively, for overall survival (OS) (P = 0.009). Postoperatively, 101 (57.1%) patients received concurrent chemoradiotherapy (CCRT) and 76 (42.9%) received radiotherapy alone (RT). CCRT was beneficial for tumors expressing only a single high-risk factor: hazard ratio (HR) for CCRT over RT alone for PFS and OS were 0.27 (95% CI 0.13–0.57, P = 0.001) and 0.31 (95% CI 0.13– 0.72, P = 0.007), respectively. The benefit of CCRT diminished when tumors expressed multiple high-risk factors: HR for PFS and OS were 0.72 (95% CI 0.37–1.38, P = 0.32) and 0.78 (95% CI 0.36–1.73, P = 0.55), respectively.
Objectives: The aim of this study was to assess the relative incidences of cervical adenocarcinoma in situ (AIS) and squamous cell carcinoma in situ (sCIS) and to determine the impact of coexisting squamous cell lesions on outcomes in patients with cervical AIS. Methods: We performed a retrospective review of patients diagnosed with AIS or sCIS who underwent conization at a university hospital between 2000 and 2011. Results: A total of 1184 patients with cervical carcinoma in situ were included. The ratio of sCIS to AIS was 16:1. Among 71 patients with AIS, AIS with coexisting squamous cell lesions and AIS alone were detected in 41 patients (58%) and 30 patients (42%), respectively. The Papanicolaou smear results before conization in patients with AIS and coexisting squamous cell lesions showed squamous, glandular, and combined cell abnormalities in 93%, 2%, and 2% of patients, respectively, whereas the Papanicolaou smear results of patients with AIS alone showed squamous, glandular, and combined cell abnormalities in 37%, 43%, and 10% of patients, respectively (P b 0.001). During the median follow-up of 57.1 months, five episodes of AIS recurrences and one episode of invasive recurrence occurred. The recurrence rate was significantly higher in patients with AIS alone than in patients with AIS and coexisting squamous cell lesions (17% vs 2%; P = 0.043). Conclusions: Patients with AIS alone on conization sample are more likely to experience recurrence, whereas patients with AIS and coexisting squamous cell lesions may be treated conservatively. doi:10.1016/j.ygyno.2014.03.169
150 — Poster Session A A new suggested pattern-based clinical classification system for endocervical adenocarcinoma N. Thomakos, M. Sotiropoulou, D. Zacharakis, I. Koutroumpa, E. Valla, S.P. Trachana, D. Haidopoulos, F. Zagouri, G. Vlachos, A. Rodolakis. Alexandra Hospital, University of Athens, Athens, Greece. Objectives: According to FIGO classification, endocervical adenocarcinoma (EAC) staging is based on tumor depth of invasion (DOI). Because EAC spreads primarily by lymphatic dissemination, treatment
Abstracts / Gynecologic Oncology 133 (2014) 2–207
of patients with EAC needs to address not only the primary tumor size but also the adjacent tissues and lymph nodes (LNs). The objective of this study was to investigate other pathologic factors that could better identify those patients at risk of developing LN metastases. Methods: A retrospective review of records of patients with EAC treated in our institution. Data regarding clinical and pathologic features, such as DOI, tumor size, lymphovascular invasion (LVI), and pattern of tumor invasion, were defined. Suggesting a newly devised system, the above parameters were categorized as followed: Pattern A: well-confined glands, disregarding DOI; Pattern B: early invasion of stroma, originating from well-confined glands; Pattern C: spread, destructive invasion. Results: A total of 103 women aged 21 to 79 years (mean, 50.67 years) were identified with EAC. All patients were staged between IA2 and IV, with DOI ranging from 3.5 to N40 mm; LVI was documented in 42 cases. To compare the standard staging method using DOI criteria and the suggested new method with patterns, we created the following table:
Standard Method Pattern A Pattern B Pattern C
Patients
Patients with
Total LN
# Pos LN
Stage I
Stage II - IV
103
Pos LN 15 (14.6%)
2281
35 (1.53%)
65 (63.1%)
38 (36.9%)
20 (19.4%) 35 (33.9%) 48 (46.7%)
0 (0%) 4 (11.4%) 11 (22.9%)
451 680 1150
0 (0%) 10 (1.5%) 25 (2.2%)
20 (100%) 25 (71.4%) 20 (41.6%)
0 (0%) 10 (28.6%) 28 (58.3%)
Conclusions: As shown, a percentage of the 19.4% of patients (Pattern A, stage I) would not need LN resection, according to the suggested histologic classification for EAC. Moreover, patients with Pattern B characteristics rarely have LN metastases because 71.4% of them have stage I disease. In contrast, patients with Pattern C should receive aggressive treatment because 22.9% of them have LN involvement. Additionally, most patients who have higher-stage disease have tumors in Pattern C. Therefore, our data suggest that this new pattern-based method of classifying EAC could be clinically significant because it is simple and consistent.
doi:10.1016/j.ygyno.2014.03.170
151 — Poster Session A Differentiation between high- and low-grade cervical intraepithelial neoplasia by p16 immunoexpression C.E.M.D.C. Andrade, M.A. Vieira, R. Dos Reis, A.T. Tsunoda, A. Longatto-Filho, C. Scapulatempo-Neto, I.D.C.G. Da Silva, J.H.T.G. Fregnani. Barretos Cancer Hospital, Barretos, Brazil. Objectives: Inter-rater disagreement may occur when differentiating high-grade from low-grade cervical intraepithelial neoplasia (CIN) in clinical routine. The use of p16 immunohistochemistry could help the pathologist to differentiate these two presentations of CIN. Methods: We performed a retrospective analysis of all consecutive cone specimens from patients who underwent surgical treatment for CIN between July 2009 and February 2011. The pathological results were classified into low-grade CIN and high-grade CIN, and these two groups were compared with p16 immunohistochemistry. p16 was considered positive when 75% of the neoplasia had moderate or strong staining. Categories were compared by means of chi-square test. A P value b0.05 was considered significant. Results: Among 277 women, 20 (7.2%) of cone specimens showed low-grade CIN and 257 (92.8%) showed high-grade CIN. In low-grade CIN histology group, 18 (90%) had negative p16 stain and 2 (10%) had positive p16 stain. In the high-grade CIN group, 72 (28%) had negative p16 stain and 185 (72%) were positive. The difference between the two groups was statistically significant (P b0.0001) (Table 1).
63
Conclusions: The use of p16 immunohistochemistry had the capacity to differentiate high-grade from low-grade CIN, and this tool should be used clinically to reduce inter-rater disagreement. Table 1. Distribution of p16 Staining by CIN Histology. p16 negative
p16 positive
n (%)
n (%)
Low-grade
18 (90%)
2 (10%)
High-grade
72 (28%)
185 (72%)
CIN Histology
P value
<0.0001
doi:10.1016/j.ygyno.2014.03.171
152 — Poster Session A Risk factors for cervical intraepithelial neoplasia (CIN) recurrence in patients with positive cone margins C.E.M.D.C. Andrade1, R. Dos Reis1, M.A. Vieira1, I.D.C.G. Da Silva1, A.T. Tsunoda1, J.H.T.G. Fregnani1, F.A. Soares2. 1Barretos Cancer Hospital, Barretos, Brazil, 2AC Camargo Cancer Center, Sao Paulo, Brazil. Objectives: Positive cone margins are an important factor related to CIN recurrence after conization, but not all women with these findings will have recurrences. We evaluated the risk factors associated with CIN recurrence after surgical treatment in patients with positive cone margins. Methods: Ninety-seven women who underwent surgery between July 2009 and February 2011 due to CIN and who had positive surgical margins at final pathology reports were analyzed. Clinical (age, tobacco consumption, and parity) and pathologic (histopathologic diagnosis and glandular extension) factors and biomarkers (high-risk human papillomavirus (HPV) detection by COBAS test® in the pretreatment cytology and p16 immunoexpression in the surgical specimen) were evaluated by univariate and multivariate analyses to determine the predictors of recurrence in 2 years. Results: The median follow-up was 22.6 months (range, 0.7– 37.5 months). There were 33 recurrences of CIN after treatment (34.0%). The 2-year disease-free survival rate was 66.3% (95% CI 56.3%– 76.3%). After univariate analysis, positive HPV-16, tobacco consumption, and age were considered for multivariate analysis. In multivariate analysis (Table 1), the single independent risk factor for recurrence was tobacco consumption (HR 3.5, 95% CI 1.6–7.6, P = 0.002). Conclusions: Women with tobacco consumption and positive surgical margins at conization had a higher risk of recurrence. Tobacco cessation is strongly recommended in this population. Table 1. Multivariate Analysis (Cox Model).
doi:10.1016/j.ygyno.2014.03.172