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Predictors of Lynch syndrome and clinical outcomes among universally screened endometrial cancer patients
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Abstracts / Gynecologic Oncology 145 (2017) 2–220
187 - Poster Session Prospective assessment of circulating tumor cells (CTCs) in women undergoing surgery for suspected ovarian cancer E. Loua, R. Isaksson Vogela, M. Gerberb, A. Gradb, M. Monub, T. Łukaszewskib, S. Hoostalb, J. Deshpandeb, D.G.K. Teoha, M. Lindenb, M.A. Gellera. aUniversity of Minnesota, Minneapolis, MN, USA, b University of Minnesota Cancer Center, Minneapolis, MN, USA Objective: Clinical assessment of circulating tumor cells (CTCs) as a blood-based biomarker is FDA-approved for use in breast, colorectal, and prostate cancer. Few studies have examined CTCs in ovarian cancer, including correlation with histopathologic diagnosis. Use of CTCs as a predictive or prognostic biomarker is a feasible clinical laboratory-based tool that could be applied clinically if validated. The objective of this prospective study was to determine whether pretreatment CTCs are a useful diagnostic biomarker in women with suspected ovarian cancers. Method: Women with newly diagnosed pelvic masses assessed at our institution were enrolled in this institutional reveiw boardapproved study. Whole blood was collected. Carcinoma cells were positively selected using magnetic beads conjugated to an antiEpCAM antibody. CTC enumeration was performed using photomicroscopic image analysis after staining cells with DAPI, anti-CD45, and an anticytokeratin cocktail. Presence of CTCs (yes/no, with enumeration of CTCs per 7.5 mL) was compared between women with and without an ovarian cancer histopathologic diagnosis using a χ2 test. Results: Blood samples were obtained from 50 patients; 93.9% underwent surgical cytoreduction. The median baseline CA-125 level was 128 (range 5–2,782). CTCs were absent in those with benign disease (0/14), present in 20% (6/30) of patients with histologic diagnosis of ovarian carcinoma, and present in 80% (4/5) of patients with malignant ovarian masses of nonovarian origin (2 Krukenberg/ GI, 1 endometrial, 1 sarcoma) (P = 0.001). Among those with primary ovarian cancer, 23.5% (4/17) with high-grade epithelial ovarian cancers had measurable CTCs, 33.3% (2/6) with low-grade epithelial cases, and none with borderline (0/5) or stromal (0/2) tumors (P = 0.59). All 6 women with ovarian cancer who had CTCs present had stage III or IV disease (0/11 with stage I/II disease vs 6/19 with stage III/IV disease, P = 0.06). Conclusion: CTCs by themselves are unlikely to be a useful diagnostic biomarker for this disease. However, CTCs were more prevalent in patients with metastases to the ovary than in primary ovarian carcinomas, suggesting that CTC enumeration may correlate with tumor burden in nonovarian malignancies that manifest with ovarian metastasis at time of diagnosis.
(IHC) staining for MMR proteins: MLH1, PMS2, MSH2, and MSH6. Tumors with lack of expression of PMS2 or MLH1 were assessed for MLH1 promotor methylation. Tumors were classified as MMR-I (intact expression of MMR proteins), MMR-DM (MMR-deficient due to MLH1 methylation), and MMR-DU (MMR-deficient without MLH1 methylation). Patients with MMR-DU were offered genetic counseling, and germline genetic testing was conducted at a commercial laboratory where appropriate. Clinical and pathologic factors predictive of MMR-DU were evaluated using univariate and multivariate analysis. Overall survival (OS) and progression-free survival (PFS) were assessed using Cox proportional hazards for patients with at least 2 years of follow-up. Results: Among 723 patients who underwent universal screening, 522 (72.2%) were MMR-I and 168 (23.2%) were MMR-DM. A total of 33 patients (4.6%) had MMR-DU. Of 27 patients who underwent genetic testing, 12 (44.4%) were confirmed to have LS. On multivariate analysis, clinical factors independently associated with MMRDU included younger age (OR = 0.97, CI 0.92–1.01, P b 0.0008) and lower BMI (OR = 0.89, CI 0.84–0.95, P = 0.0017). In addition, MMRDU tumors were more likely to be grade 3 or grade 2 versus grade 1 (OR = 4.67, CI 1.51–14.5; OR = 79.25, CI 18.42–340.98, respectively, P b 0.0001), endometrioid histology (OR = 1.51, 0.92–2.50, P = −0.046), b50% myometrial invasion (OR = 6.65, CI 1.56–28.3, P = 0.037), and b2 cm tumor size (OR = 2.18, CI 0.80–5.89, P = 0.014). Family history, menopausal status, race, lymphovascular space invasion, and stage were not predictive of MMR-DU status. There was no difference in overall survival or progression-free survival based on MMR or LS status (P = NS). Conclusion: Application of clinical and pathologic criteria may help stratify patients at highest risk for LS among those undergoing universal screening. These factors can be used to develop a risk prediction model to guide clinical counseling and genetic testing. doi:10.1016/j.ygyno.2017.03.216
189 - Poster Session Sentinel lymph node biopsy for early cervical cancer: Five years follow-up of a diagnostic, prospective, multicenter study (Senticol 1) P. Matheveta, M. Dorezb, F. Lecuruc, P. Moriced, D. Querleue, L. Magaudf, E. Daraïg, E. Leblanch. aCHU Vaudois, Lausanne, Switzerland, b CHU Nice, Nice, France, cHôpital Européen Georges-Pompidou, Paris, France, dInstitut Gustave Roussy, Villejuif, France, eInstitut Bergonié Cancer Center, Bordeaux, France, fHospices Civils de Lyon, Bron, France, g Assistance Publique de Paris, Paris, France, hCentre Oscar Lambret, Lille, France
doi:10.1016/j.ygyno.2017.03.215
188 - Poster Session Predictors of Lynch syndrome and clinical outcomes among universally screened endometrial cancer patients M.M. AlHillia, C.E. Carra, A. Priyadarshinib, M. Radevab, J. Marquardb. a The Cleveland Clinic Foundation, Cleveland, OH, USA, bCleveland Clinic, Cleveland, OH, USA Objective: To determine the clinicopathologic characteristics associated with a probable diagnosis of Lynch syndrome (LS) among patients undergoing universal LS screening. Method: From August 2012 to August 2015, all patients diagnosed with EC underwent screening for LS using immunohistochemistry
Objective: Sentinel lymph node (SLN) biopsy is now part of management of cervical cancer. This approach was validated through several retrospective and prospective studies. We present the 5-year follow-up of a prospective multicenter study in France (Senticol 1 study). Method: Senticol 1 study has been carried out between January 2005 and June 2007. Inclusion criteria were FIGO stage IA/IB1 cervical cancer; histology squamous, adenocarcinoma, and adenosquamous; patient age N18 years. All patients underwent SLN identification with a combined method (technetium + patent blue) followed by full pelvic ± paraaortic lymphadenectomy. All the procedures were performed by laparoscopy. The protocol has been funded by the French National Institute of Cancer and has been reviewed by an ethical committee. The main objective of the study has already been published. Research of micrometastasis was performed secondary on the SLN and did not affect the adjuvant treatments performed based
Abstracts / Gynecologic Oncology 145 (2017) 2–220
187 - Poster Session Prospective assessment of circulating tumor cells (CTCs) in women undergoing surgery for suspected ovarian cancer E. Loua, R. Isaksson Vogela, M. Gerberb, A. Gradb, M. Monub, T. Łukaszewskib, S. Hoostalb, J. Deshpandeb, D.G.K. Teoha, M. Lindenb, M.A. Gellera. aUniversity of Minnesota, Minneapolis, MN, USA, b University of Minnesota Cancer Center, Minneapolis, MN, USA Objective: Clinical assessment of circulating tumor cells (CTCs) as a blood-based biomarker is FDA-approved for use in breast, colorectal, and prostate cancer. Few studies have examined CTCs in ovarian cancer, including correlation with histopathologic diagnosis. Use of CTCs as a predictive or prognostic biomarker is a feasible clinical laboratory-based tool that could be applied clinically if validated. The objective of this prospective study was to determine whether pretreatment CTCs are a useful diagnostic biomarker in women with suspected ovarian cancers. Method: Women with newly diagnosed pelvic masses assessed at our institution were enrolled in this institutional reveiw boardapproved study. Whole blood was collected. Carcinoma cells were positively selected using magnetic beads conjugated to an antiEpCAM antibody. CTC enumeration was performed using photomicroscopic image analysis after staining cells with DAPI, anti-CD45, and an anticytokeratin cocktail. Presence of CTCs (yes/no, with enumeration of CTCs per 7.5 mL) was compared between women with and without an ovarian cancer histopathologic diagnosis using a χ2 test. Results: Blood samples were obtained from 50 patients; 93.9% underwent surgical cytoreduction. The median baseline CA-125 level was 128 (range 5–2,782). CTCs were absent in those with benign disease (0/14), present in 20% (6/30) of patients with histologic diagnosis of ovarian carcinoma, and present in 80% (4/5) of patients with malignant ovarian masses of nonovarian origin (2 Krukenberg/ GI, 1 endometrial, 1 sarcoma) (P = 0.001). Among those with primary ovarian cancer, 23.5% (4/17) with high-grade epithelial ovarian cancers had measurable CTCs, 33.3% (2/6) with low-grade epithelial cases, and none with borderline (0/5) or stromal (0/2) tumors (P = 0.59). All 6 women with ovarian cancer who had CTCs present had stage III or IV disease (0/11 with stage I/II disease vs 6/19 with stage III/IV disease, P = 0.06). Conclusion: CTCs by themselves are unlikely to be a useful diagnostic biomarker for this disease. However, CTCs were more prevalent in patients with metastases to the ovary than in primary ovarian carcinomas, suggesting that CTC enumeration may correlate with tumor burden in nonovarian malignancies that manifest with ovarian metastasis at time of diagnosis.
(IHC) staining for MMR proteins: MLH1, PMS2, MSH2, and MSH6. Tumors with lack of expression of PMS2 or MLH1 were assessed for MLH1 promotor methylation. Tumors were classified as MMR-I (intact expression of MMR proteins), MMR-DM (MMR-deficient due to MLH1 methylation), and MMR-DU (MMR-deficient without MLH1 methylation). Patients with MMR-DU were offered genetic counseling, and germline genetic testing was conducted at a commercial laboratory where appropriate. Clinical and pathologic factors predictive of MMR-DU were evaluated using univariate and multivariate analysis. Overall survival (OS) and progression-free survival (PFS) were assessed using Cox proportional hazards for patients with at least 2 years of follow-up. Results: Among 723 patients who underwent universal screening, 522 (72.2%) were MMR-I and 168 (23.2%) were MMR-DM. A total of 33 patients (4.6%) had MMR-DU. Of 27 patients who underwent genetic testing, 12 (44.4%) were confirmed to have LS. On multivariate analysis, clinical factors independently associated with MMRDU included younger age (OR = 0.97, CI 0.92–1.01, P b 0.0008) and lower BMI (OR = 0.89, CI 0.84–0.95, P = 0.0017). In addition, MMRDU tumors were more likely to be grade 3 or grade 2 versus grade 1 (OR = 4.67, CI 1.51–14.5; OR = 79.25, CI 18.42–340.98, respectively, P b 0.0001), endometrioid histology (OR = 1.51, 0.92–2.50, P = −0.046), b50% myometrial invasion (OR = 6.65, CI 1.56–28.3, P = 0.037), and b2 cm tumor size (OR = 2.18, CI 0.80–5.89, P = 0.014). Family history, menopausal status, race, lymphovascular space invasion, and stage were not predictive of MMR-DU status. There was no difference in overall survival or progression-free survival based on MMR or LS status (P = NS). Conclusion: Application of clinical and pathologic criteria may help stratify patients at highest risk for LS among those undergoing universal screening. These factors can be used to develop a risk prediction model to guide clinical counseling and genetic testing. doi:10.1016/j.ygyno.2017.03.216
189 - Poster Session Sentinel lymph node biopsy for early cervical cancer: Five years follow-up of a diagnostic, prospective, multicenter study (Senticol 1) P. Matheveta, M. Dorezb, F. Lecuruc, P. Moriced, D. Querleue, L. Magaudf, E. Daraïg, E. Leblanch. aCHU Vaudois, Lausanne, Switzerland, b CHU Nice, Nice, France, cHôpital Européen Georges-Pompidou, Paris, France, dInstitut Gustave Roussy, Villejuif, France, eInstitut Bergonié Cancer Center, Bordeaux, France, fHospices Civils de Lyon, Bron, France, g Assistance Publique de Paris, Paris, France, hCentre Oscar Lambret, Lille, France
doi:10.1016/j.ygyno.2017.03.215
188 - Poster Session Predictors of Lynch syndrome and clinical outcomes among universally screened endometrial cancer patients M.M. AlHillia, C.E. Carra, A. Priyadarshinib, M. Radevab, J. Marquardb. a The Cleveland Clinic Foundation, Cleveland, OH, USA, bCleveland Clinic, Cleveland, OH, USA Objective: To determine the clinicopathologic characteristics associated with a probable diagnosis of Lynch syndrome (LS) among patients undergoing universal LS screening. Method: From August 2012 to August 2015, all patients diagnosed with EC underwent screening for LS using immunohistochemistry
Objective: Sentinel lymph node (SLN) biopsy is now part of management of cervical cancer. This approach was validated through several retrospective and prospective studies. We present the 5-year follow-up of a prospective multicenter study in France (Senticol 1 study). Method: Senticol 1 study has been carried out between January 2005 and June 2007. Inclusion criteria were FIGO stage IA/IB1 cervical cancer; histology squamous, adenocarcinoma, and adenosquamous; patient age N18 years. All patients underwent SLN identification with a combined method (technetium + patent blue) followed by full pelvic ± paraaortic lymphadenectomy. All the procedures were performed by laparoscopy. The protocol has been funded by the French National Institute of Cancer and has been reviewed by an ethical committee. The main objective of the study has already been published. Research of micrometastasis was performed secondary on the SLN and did not affect the adjuvant treatments performed based