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Frozen section is inaccurate at predicting need for staging in endometrial cancer
378
ABSTRACTS / Gynecologic Oncology 111 (2008) 373–386
demographics, procedural information, and postoperative course were obtained from patient hospital and office records. SAS 9.1 was utilized to generate frequencies and linear regression models. Results. There were 639 patients involved with no exclusions. The most common procedures performed, in order of frequency, included: hysterectomy with bilateral/unilateral salpingooophorectomy (261); hysterectomy with bilateral salphingooophorectomy and lymph node dissection (201); unilateral or bilateral salphingo-oophorectomy (70); and radical and modified radical hysterectomy (28). The mean operative time for all procedures was 127 min (SD = 82.1) and estimated blood loss was 67.3 cm3 (SD = 87.1). The mean age of patients was 55 years of age, mean body mass index was 29.9 (SD 8.0), node count 12.0 (SD 11.73) and hospital stay was 1.33 days (SD 0.92). The total number of intra-operative complications was 18 (2.8%) with the most common including vascular (0.63%), bladder (0.63%) and bowel (0.63%). Postoperative complications occurred in 21 (3.3%) patients, with the most common including vaginal cuff dehiscence (0.78%), DVT/PE (0.63%) and genitourinary infections (0.63%). The conversion to laparotomy rate was 3.8% with the most common reasons being uterine size (1.1%), adhesions (0.94%) and need for staging (0.94%). Of the 639 procedures, 495 involved a form of hysterectomy. The operative times (min) by procedure type were as follows: hysterectomy with bilateral/unilateral salpingo-oophorectomy 113 (SD = 70), hysterectomy with bilateral salphingo-oophorectomy and lymphadenectomy 155 (SD = 70), radical hysterectomy with lymphadenectomy 217 (SD = 128), modified radical hysterectomy with lymphadenectomy 180 (SD = 0.0), and simple hysterectomy (N = 5). Mean operative time for each procedure (min) in order:),), and Estimated blood loss (EBL) decreased for one physician, while operative time decreased for three of the physicians. Conclusions. The da Vinci Robotic Surgical System provides gynecologic oncologists with a minimally invasive option for performing multiple surgical procedures while minimizing operative time and blood loss. Operative time seems to improve with each sequential case; however, EBL decreases rapidly with the first several cases but is less easily improved after this milestone.
(PR) expression is common in uterine sarcomas and that hormonal therapy would be an effective treatment option. Methods. Under an IRB-approved protocol we retrospectively reviewed 46 charts of patients with uterine sarcomas. Information on patient demographics, surgico-pathologic features and outcomes were abstracted. We reviewed the treatment and recurrence patterns with specific focus on hormonal treatment of both primary and recurrent disease. Results. 8 patients with ESS were treated with hormone therapy of which 7 were low grade ESS and ER/PR positive. 4 of these patients had adjuvant hormone therapy: 2 received aromatase inhibitors (AI) and remain without disease for 16– 40 months and 1 received Megace and remains without disease for 149 months. 2 patients with recurrent ESS have had sustained clinical responses on AI: one CR for 54 months and 1 PR for 60 months. 8 pts with ER positive leiomyosarcoma (LMS) have been treated with hormone therapy. 3 of these patients received AI as adjuvant treatment and remain without evidence of disease for 18 to 68 months. 5 patients with recurrent LMS received salvage hormone therapy of whom 4 had stable disease sustained for 12–60 months: 3 treated with AI and 1 treated with Tamoxifen. 3 pts with mixed mesodermal mullerian tumors (MMMT) whose ER/PR status was not tested were treated with hormones as salvage therapy for recurrent disease. 2 of these patients had stable disease for 4 months with Megace and Tamoxifen. 1 patient with ER positive adenosarcoma (AS) treated with adjuvant Tamoxifen remains without evidence of disease at 23 months. There were no reported grade 3 or 4 toxicities with any hormonal therapy. Conclusions. The majority of patients, 26/29 (90%), with uterine sarcomas whose receptor status was tested were ER/PR positive. Thus, routine staining for ER/PR status is advised. We report durable responses to AI in 2 patients with recurrent ESS and disease stabilization with Tamoxifen and Megace in the majority of treated patients. Given the minimal toxicity and ease of administration associated with these medications, hormonal therapy should be considered as salvage therapy for recurrent uterine sarcomas. Future investigation of hormonal therapy as adjuvant treatment is warranted.
doi:10.1016/j.ygyno.2008.07.073
doi:10.1016/j.ygyno.2008.07.074
11 Hormonal therapies demonstrate high response rates in treatment of recurrent uterine sarcomas Y.J. Ioffe, A.J. Li, C. Walsh, B.Y. Karlan, R. Leuchter, I. Cass Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, CA, USA
12 Frozen section is inaccurate at predicting need for staging in endometrial cancer A. Papadia a, G. Azioni b, K. Nishida a, S. Seitz c, S. Bucholz c, B. Brusacà b, E. Fulcheri b, N. Ragni b, E. Jimenez a, J.A. Lucci III a a University of Miami Miller School of Medicine, USA b University of Genova, Italy c University of Regensburg, Germany
Objectives. Uterine sarcomas are a heterogeneous group of tumors with a highly variable clinical course. While hormonal approaches have been reported to be effective in the treatment of low-grade endometrial stromal sarcomas (ESS), their utility in treating other higher grade uterine sarcomas remains unknown. We hypothesized that estrogen and progesterone receptor (ER)/
Objective. To evaluate accuracy of intraoperative frozen section (FS) at identifying risk for lymph node involvement when compared with final pathology.
ABSTRACTS / Gynecologic Oncology 111 (2008) 373–386
Methods. Pathologic records of patients with type I EC on whom an intraoperative FS of the uterus was performed at a single institution between 1995 and 2006 were reviewed. The risk for pelvic and paraaortic lymph node metastases was determined at frozen and permanent section (PS), and defined as low, intermediate and high based on a combination of tumor grade and myometrial invasion as described in GOG # 33. The agreement between risk attribution at FS and PS was calculated with Kappa of concordance. Additionally, agreement between risk attribution based on tumor grade at preoperative endometrial (EMB) biopsy (performed either with pipelle only or with D&C) and myometrial invasion estimated at FS and PS was calculated. Results. There were 182 and 147 cases respectively, in which attribution of risk based on myometrial invasion and tumor grading at FS and at EMB and FS was possible. At FS myometrial invasion was absent, b 50%, and N 50% in 33, 96 and 54 cases respectively; tumor grade was 1, 2 and 3 in 115, 27 and 15 cases respectively. At PS myometrial invasion was absent, b 50%, and N 50% in 20, 105 and 57 cases respectively; tumor grade was 1, 2 and 3 in 114, 53 and 14 cases respectively. At FS 111, 18 and 53 patients were considered at low, intermediate and high risk respectively. At PS 91, 34 and 57 patients were considered at low, intermediate and high risk respectively. Observed agreement between FS and PS was good with a Kappa value of 0.625. If FS were the only criterion considered for surgical staging, 16% of the patients would have missed part of an indicated procedure. The concordance of risk attribution based on preoperative tumor grade combined with myometrial invasion by FS compared with PS was very low (Kappa = − 0.006). Conclusions. In 16% of cases, frozen section did not accurately predict final pathology. Therefore, frozen section should not be routinely used to identify patients with endometrial cancer who would benefit from surgical staging. doi:10.1016/j.ygyno.2008.07.075
13 Multi-institutional study identifying predictors of response to progestin treatment of complex atypical hyperplasia or grade 1 endometrial adenocarcinoma K. Penner, O. Dorigo, C. Walsh, I. Cass, C. Holschneider UCLA, Olive View, and Cedars Sinai Medical Centers, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA Objective. Five to 10% of endometrial adenocarcinomas occur in premenopausal women. The pathological distinction between well differentiated endometrial cancer (G1EAC) and complex atypical hyperplasia (CAH) is challenging. For young women who desire fertility preservation, progestin therapy is a treatment option; however, predictors of response to treatment are unknown. We hypothesized that certain patient characteristics could predict the outcome of progestin therapy for patients with CAH and G1EAC.
379
Methods. Premenopausal patients diagnosed with CAH or G1EAC were retrospectively identified in a multi-institutional IRB approved study from 1998–2008. Data was extracted including patient characteristics, type and length of progesterone therapy and response to treatment. Response to therapy is defined as absence of atypia. Resolution is defined as two sequential biopsies or a hysterectomy specimen negative for hyperplasia or cancer. Progestin therapy included any progestogen. Patients were excluded if they had significant confounding risk factors, including hormonal treatment of breast cancer, prior gynecologic malignancy, and pelvic radiation. Results. 48 subjects were identified. Median age at first biopsy was 35.5 years (range 23–48). 76% were nulliparous and 44% had a BMI ≥35. On initial sampling, pathology showed G1EAC in 44% and CAH in 56% of subjects. 81% received oral progestins; 19% were treated with a levonorgestrel releasing intrauterine system. Overall response rate was 55%; rate of resolution was 48%. Median time to response was 5 months; median time to resolution was 6 months. Of the 27 subjects with CAH, 67% showed response, 60% resolution. For the 21 patients with G1EAC, the response rate was 38% with a rate of resolution of 33%. An initial diagnosis of G1EAC showed a trend towards a higher risk of persistence or progression (OR 2.9, p=.09). No significant difference in either response rate (p=0.99) or resolution (p=0.72) was seen when comparing treatment with oral progestins to the levonorgestrel releasing intrauterine system or when stratifying by age ≥35 (p=0.77). A trend toward both increased response (p= 0.11) and resolution (pb 0.10) was noted in patients with a BMI b 35. Conclusions. This study confirms a 60% resolution rate for CAH, but shows a significantly lower resolution rate for G1EAC (33%) with progestin therapy. While the two diagnoses share many histological features, the disparity in the observed resolution rate may suggest molecular differences that influence response to progestin therapy. The negative association between BMI and response/resolution rates may indicate a need for weight-based dosing. The use of the levonorgestrel releasing intrauterine system in treating CAH and G1EAC appears to have success rates comparable to oral progestin treatments. Patients with CAH or G1EAC being treated conservatively with progestin therapy merit close follow up. doi:10.1016/j.ygyno.2008.07.076
14 The effect of gynecologic oncologists on the survival of endometrial cancer patients H. Deshmukh a, R. Zhang a, X. Yu b, J.Y. Shin a, K. Osann c, A. Mariani d, D.S. Kapp e, A. Husain e, L. Chen a, J.K. Chan a a University of California, San Francisco School of Medicine, San Francisco, CA, USA b University of Minnesota, Minneapolis, MN, USA c University of California, Irvine Medical Center, Orange, CA, USA d Mayo Clinic, Rochester, MN, USA e Stanford University School of Medicine, Stanford, CA, USA
ABSTRACTS / Gynecologic Oncology 111 (2008) 373–386
demographics, procedural information, and postoperative course were obtained from patient hospital and office records. SAS 9.1 was utilized to generate frequencies and linear regression models. Results. There were 639 patients involved with no exclusions. The most common procedures performed, in order of frequency, included: hysterectomy with bilateral/unilateral salpingooophorectomy (261); hysterectomy with bilateral salphingooophorectomy and lymph node dissection (201); unilateral or bilateral salphingo-oophorectomy (70); and radical and modified radical hysterectomy (28). The mean operative time for all procedures was 127 min (SD = 82.1) and estimated blood loss was 67.3 cm3 (SD = 87.1). The mean age of patients was 55 years of age, mean body mass index was 29.9 (SD 8.0), node count 12.0 (SD 11.73) and hospital stay was 1.33 days (SD 0.92). The total number of intra-operative complications was 18 (2.8%) with the most common including vascular (0.63%), bladder (0.63%) and bowel (0.63%). Postoperative complications occurred in 21 (3.3%) patients, with the most common including vaginal cuff dehiscence (0.78%), DVT/PE (0.63%) and genitourinary infections (0.63%). The conversion to laparotomy rate was 3.8% with the most common reasons being uterine size (1.1%), adhesions (0.94%) and need for staging (0.94%). Of the 639 procedures, 495 involved a form of hysterectomy. The operative times (min) by procedure type were as follows: hysterectomy with bilateral/unilateral salpingo-oophorectomy 113 (SD = 70), hysterectomy with bilateral salphingo-oophorectomy and lymphadenectomy 155 (SD = 70), radical hysterectomy with lymphadenectomy 217 (SD = 128), modified radical hysterectomy with lymphadenectomy 180 (SD = 0.0), and simple hysterectomy (N = 5). Mean operative time for each procedure (min) in order:),), and Estimated blood loss (EBL) decreased for one physician, while operative time decreased for three of the physicians. Conclusions. The da Vinci Robotic Surgical System provides gynecologic oncologists with a minimally invasive option for performing multiple surgical procedures while minimizing operative time and blood loss. Operative time seems to improve with each sequential case; however, EBL decreases rapidly with the first several cases but is less easily improved after this milestone.
(PR) expression is common in uterine sarcomas and that hormonal therapy would be an effective treatment option. Methods. Under an IRB-approved protocol we retrospectively reviewed 46 charts of patients with uterine sarcomas. Information on patient demographics, surgico-pathologic features and outcomes were abstracted. We reviewed the treatment and recurrence patterns with specific focus on hormonal treatment of both primary and recurrent disease. Results. 8 patients with ESS were treated with hormone therapy of which 7 were low grade ESS and ER/PR positive. 4 of these patients had adjuvant hormone therapy: 2 received aromatase inhibitors (AI) and remain without disease for 16– 40 months and 1 received Megace and remains without disease for 149 months. 2 patients with recurrent ESS have had sustained clinical responses on AI: one CR for 54 months and 1 PR for 60 months. 8 pts with ER positive leiomyosarcoma (LMS) have been treated with hormone therapy. 3 of these patients received AI as adjuvant treatment and remain without evidence of disease for 18 to 68 months. 5 patients with recurrent LMS received salvage hormone therapy of whom 4 had stable disease sustained for 12–60 months: 3 treated with AI and 1 treated with Tamoxifen. 3 pts with mixed mesodermal mullerian tumors (MMMT) whose ER/PR status was not tested were treated with hormones as salvage therapy for recurrent disease. 2 of these patients had stable disease for 4 months with Megace and Tamoxifen. 1 patient with ER positive adenosarcoma (AS) treated with adjuvant Tamoxifen remains without evidence of disease at 23 months. There were no reported grade 3 or 4 toxicities with any hormonal therapy. Conclusions. The majority of patients, 26/29 (90%), with uterine sarcomas whose receptor status was tested were ER/PR positive. Thus, routine staining for ER/PR status is advised. We report durable responses to AI in 2 patients with recurrent ESS and disease stabilization with Tamoxifen and Megace in the majority of treated patients. Given the minimal toxicity and ease of administration associated with these medications, hormonal therapy should be considered as salvage therapy for recurrent uterine sarcomas. Future investigation of hormonal therapy as adjuvant treatment is warranted.
doi:10.1016/j.ygyno.2008.07.073
doi:10.1016/j.ygyno.2008.07.074
11 Hormonal therapies demonstrate high response rates in treatment of recurrent uterine sarcomas Y.J. Ioffe, A.J. Li, C. Walsh, B.Y. Karlan, R. Leuchter, I. Cass Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, CA, USA
12 Frozen section is inaccurate at predicting need for staging in endometrial cancer A. Papadia a, G. Azioni b, K. Nishida a, S. Seitz c, S. Bucholz c, B. Brusacà b, E. Fulcheri b, N. Ragni b, E. Jimenez a, J.A. Lucci III a a University of Miami Miller School of Medicine, USA b University of Genova, Italy c University of Regensburg, Germany
Objectives. Uterine sarcomas are a heterogeneous group of tumors with a highly variable clinical course. While hormonal approaches have been reported to be effective in the treatment of low-grade endometrial stromal sarcomas (ESS), their utility in treating other higher grade uterine sarcomas remains unknown. We hypothesized that estrogen and progesterone receptor (ER)/
Objective. To evaluate accuracy of intraoperative frozen section (FS) at identifying risk for lymph node involvement when compared with final pathology.
ABSTRACTS / Gynecologic Oncology 111 (2008) 373–386
Methods. Pathologic records of patients with type I EC on whom an intraoperative FS of the uterus was performed at a single institution between 1995 and 2006 were reviewed. The risk for pelvic and paraaortic lymph node metastases was determined at frozen and permanent section (PS), and defined as low, intermediate and high based on a combination of tumor grade and myometrial invasion as described in GOG # 33. The agreement between risk attribution at FS and PS was calculated with Kappa of concordance. Additionally, agreement between risk attribution based on tumor grade at preoperative endometrial (EMB) biopsy (performed either with pipelle only or with D&C) and myometrial invasion estimated at FS and PS was calculated. Results. There were 182 and 147 cases respectively, in which attribution of risk based on myometrial invasion and tumor grading at FS and at EMB and FS was possible. At FS myometrial invasion was absent, b 50%, and N 50% in 33, 96 and 54 cases respectively; tumor grade was 1, 2 and 3 in 115, 27 and 15 cases respectively. At PS myometrial invasion was absent, b 50%, and N 50% in 20, 105 and 57 cases respectively; tumor grade was 1, 2 and 3 in 114, 53 and 14 cases respectively. At FS 111, 18 and 53 patients were considered at low, intermediate and high risk respectively. At PS 91, 34 and 57 patients were considered at low, intermediate and high risk respectively. Observed agreement between FS and PS was good with a Kappa value of 0.625. If FS were the only criterion considered for surgical staging, 16% of the patients would have missed part of an indicated procedure. The concordance of risk attribution based on preoperative tumor grade combined with myometrial invasion by FS compared with PS was very low (Kappa = − 0.006). Conclusions. In 16% of cases, frozen section did not accurately predict final pathology. Therefore, frozen section should not be routinely used to identify patients with endometrial cancer who would benefit from surgical staging. doi:10.1016/j.ygyno.2008.07.075
13 Multi-institutional study identifying predictors of response to progestin treatment of complex atypical hyperplasia or grade 1 endometrial adenocarcinoma K. Penner, O. Dorigo, C. Walsh, I. Cass, C. Holschneider UCLA, Olive View, and Cedars Sinai Medical Centers, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA Objective. Five to 10% of endometrial adenocarcinomas occur in premenopausal women. The pathological distinction between well differentiated endometrial cancer (G1EAC) and complex atypical hyperplasia (CAH) is challenging. For young women who desire fertility preservation, progestin therapy is a treatment option; however, predictors of response to treatment are unknown. We hypothesized that certain patient characteristics could predict the outcome of progestin therapy for patients with CAH and G1EAC.
379
Methods. Premenopausal patients diagnosed with CAH or G1EAC were retrospectively identified in a multi-institutional IRB approved study from 1998–2008. Data was extracted including patient characteristics, type and length of progesterone therapy and response to treatment. Response to therapy is defined as absence of atypia. Resolution is defined as two sequential biopsies or a hysterectomy specimen negative for hyperplasia or cancer. Progestin therapy included any progestogen. Patients were excluded if they had significant confounding risk factors, including hormonal treatment of breast cancer, prior gynecologic malignancy, and pelvic radiation. Results. 48 subjects were identified. Median age at first biopsy was 35.5 years (range 23–48). 76% were nulliparous and 44% had a BMI ≥35. On initial sampling, pathology showed G1EAC in 44% and CAH in 56% of subjects. 81% received oral progestins; 19% were treated with a levonorgestrel releasing intrauterine system. Overall response rate was 55%; rate of resolution was 48%. Median time to response was 5 months; median time to resolution was 6 months. Of the 27 subjects with CAH, 67% showed response, 60% resolution. For the 21 patients with G1EAC, the response rate was 38% with a rate of resolution of 33%. An initial diagnosis of G1EAC showed a trend towards a higher risk of persistence or progression (OR 2.9, p=.09). No significant difference in either response rate (p=0.99) or resolution (p=0.72) was seen when comparing treatment with oral progestins to the levonorgestrel releasing intrauterine system or when stratifying by age ≥35 (p=0.77). A trend toward both increased response (p= 0.11) and resolution (pb 0.10) was noted in patients with a BMI b 35. Conclusions. This study confirms a 60% resolution rate for CAH, but shows a significantly lower resolution rate for G1EAC (33%) with progestin therapy. While the two diagnoses share many histological features, the disparity in the observed resolution rate may suggest molecular differences that influence response to progestin therapy. The negative association between BMI and response/resolution rates may indicate a need for weight-based dosing. The use of the levonorgestrel releasing intrauterine system in treating CAH and G1EAC appears to have success rates comparable to oral progestin treatments. Patients with CAH or G1EAC being treated conservatively with progestin therapy merit close follow up. doi:10.1016/j.ygyno.2008.07.076
14 The effect of gynecologic oncologists on the survival of endometrial cancer patients H. Deshmukh a, R. Zhang a, X. Yu b, J.Y. Shin a, K. Osann c, A. Mariani d, D.S. Kapp e, A. Husain e, L. Chen a, J.K. Chan a a University of California, San Francisco School of Medicine, San Francisco, CA, USA b University of Minnesota, Minneapolis, MN, USA c University of California, Irvine Medical Center, Orange, CA, USA d Mayo Clinic, Rochester, MN, USA e Stanford University School of Medicine, Stanford, CA, USA