- Email: [email protected]
Treatment of women with intermediate risk endometrial cancer
Abstracts / Gynecologic Oncology 125 (2012) S3–S167
Objective: Despite the armamentarium of cytotoxic agents in the management of all gynecological cancers, enthusiasm for these agents has been tempered the emergence of resistance. The vascular endothelial factor and the mammalian target of rapamycin (mTOR) have emerged as attractive targets for the design of targeted therapeutics. Investigators have reported alterations in PTEN in gynecological malignancies. The loss of functional PTEN either through deletion, mutation or inactivation leads to the constitutive activation of PI3K effectors in the absence of exogenous stimuli. The frequent loss of PTEN function suggests mTOR inhibition as a rational targeted therapy regulating tumor growth and angiogenesis through VEGF and HIF-1 expression. We conducted a phase I study to evaluate the safety and the therapeutic strategy of targeting the mTOR and VEGF pathway in patients with gynecological malignancies. The objective was to establish a suitable dose for further exploration in a phase II study. Methods: Phase-1 trial using a 3 + 3 step-up dose escalation design. The MTD was defined within one cycle of therapy. 4 dose levels were planned. Dose level 1: Temsirolimus 10 mg IV and Cedarinib 15 mg PO; dose level 2: Temsirolimus 20 mg IV and Cedarinib 15 mg PO; dose level 3: Temsirolimus 20 mg IV and Cedarinib 20 mg PO; dose level 4: Temsirolimus 20 mg IV and Cedarinib 25 mg PO. Results: Study was amended after 2 patients experienced a dose limiting toxicity in cohort 1. Dose limiting toxicities were primarily hematological but also include nonhematological toxicity — namely elevated liver function tests. After IRB approval the study was amended to limit the number of prior lines. Three additional patients were accrued, two patients triggered a DLT as a result of elevated triglycerides. The study was closed to further accrual. Of note four patients experienced SD . One patient with cervical cancer remained stable for 9 months. Conclusions: mTOR is central to gynecological malignancies and represents a pathway that stands at the intersection of multiple important signaling pathways. Tumorgenesis is navigated by redundant pathways. This trial demonstrated that these two pathways may convergence given the increased toxicity observed in cohort 1. Several patients did have stable disease. It is conceivable that the combination of both a mTor inhibitor and a VEGF inhibitor may still hold some value in a selected population.
S79
Objective: Two recent clinical trials evaluating therapeutic HPV vaccines have reported complete responses in excess of 40% of vaccinated subjects with VIN, over a 52-week study window. These trials demonstrate that regression of established high grade intraepithelial lesions can occur in subjects with modest systemic responses detectable after ex vivo stimulation with viral antigens, and that responses “accumulated” over a longer timeframe than is typically used in trial design. We sought to evaluate a novel HPV16E7 vaccine in patients with CIN3. Methods: A phase I trial is being conducted testing intradermal, intracervical, and intramuscular routes of administration of a DNA vaccine targeting HPV16E7, in subjects with HPV16 + CIN3, prior to LEEP 8 weeks post-vaccination. Clinical trial endpoints include assessment of regression of CIN, and immune response. Results: To date, 9 patients have been enrolled onto 2 dose cohorts (intradermal administration). No significant vaccine-associated toxicity has been noted. Although no complete regressions have occurred, interim within-subject analyses of tissue specimens from the first dose cohort demonstrate an increase in cervical CD8+ infiltrates preand post-vaccination, resulting in an increased ratio of CD8:Treg cells. The density of Tbet+ infiltrates increased an average of 4.6-fold in lesional epithelium and by 7.6-fold in lesional stroma. The distribution of Tregs was greater in lesional stroma compared to epithelium at both timepoints. Conclusions: As expected, the DNA vaccine administered intradermally is well tolerated. Increased densities of Tbet+ cells in both the stromal and epithelial compartment of cervical mucosa suggest the generation of type I immunity. The distribution of Tregs suggests that the stromal compartment may play a role in conditioning immune responses in persistent mucosal HPV infections. Accrual to this trial is ongoing. Supported by NCI P50CA098252, NIH CTSA UL1RR025005, the Dana Foundation, NCI R21CA128232, NCI R01CA142691, and NCI P30CA006973.
doi:10.1016/j.ygyno.2011.12.190
Clinical Trials - Uterine Cancer/Endometrial/Sarcoma, Phase II/III Toxicity
G1
G2
G3
G4
Heme Non heme Nervous Cardiac Renal ID GI Endocrine Metabolic Constitutional Pain Muscle Pulmonary Derm
12
3
2
0
8 1 1 0 31 0 23 10 7 0 5 10
1 6 3 4 9 1 6 6 2 1 0 0
0 3 0 0 1 0 3 0 1 0 1 0
0 0 0 0 0 0 0 0 0 0 1 0
doi:10.1016/j.ygyno.2011.12.189
189 Location, location, location: Immune responses in patients with CIN3 receiving therapeutic HPV16E7 vaccination C. Trimble1, C. Hung1, S. Peng1, T. Wu1, W. Huh2, E. Partridge2, L. Maldonado1, N. Barat1, R. Alvarez2. 1Johns Hopkins Medical Institutions, Baltimore, MD, 2University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham, AL.
190 Treatment of women with intermediate risk endometrial cancer J. Geisler, T. Harvey, G. Phibbs, K. Manahan. University of Toledo Medical Center, Toledo, OH. Objective: Randomized trials have sought to analyze the survival differences among treatment strategies for women with intermediate risk stage I endometrial cancer (IREC) after total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAHBSO) with or without pelvic and para-aortic lymph node dissection (LND).We sought to evaluate the cost effectiveness of these strategies. Methods: A decision model was developed based on Gynecologic Oncology Group (GOG) protocol 99 along with the ASTEC and PORTEC studies. Regimen 1 is TAHBSO with radiation therapy (XRT) (TAHBSO XRT). Regimen 2 is TAHBSO LND. Regimen 3 is TAHBSO LND with XRT for intermediate risks. Cost effectiveness analysis (CEA) was performed using data from Medicare and published studies incorporating costs, complications, recurrence rates, complications, and survival. Incremental cost to effectiveness ratios (IC/IE) was determined by any nondominated treatment options. Sensitivity analyses were performed. Results: The average cost per patient for TAHBSO LND XRT was $26,142; TAHBSO XRT was $24,942; and TAHBSO LND was $7187. TAHBSO XRT had both increased cost and decreased effectiveness compared to TAHBSO LND. The IC/IE between TAHBSO LND XRT and TAHBSO LND was $2,367,243 per percentage of 5 year survival. Although TAHBSO XRT was
S80
Abstracts / Gynecologic Oncology 125 (2012) S3–S167
dominated in analysis, a one-way sensitivity analysis was performed for comparison demonstrating that 5 year survival would have to be greater than 100% for TAHBSO XRT to be cost effective. Conclusions: Performing TAHBSO LND without radiation for IREC is the most cost effective treatment; therefore, TAHBSO XRT should not be recommended as treatment.
GTD/Vulvar & Vaginal Cancers/Rare Tumors
doi:10.1016/j.ygyno.2011.12.191
Objective: To update the treatment of brain metastases in GTN at our center comparing treatment and outcomes from 1962 to 1994 (Radiology 196; 200: 277–280) with those from 1995 to 2009. Methods: Thirty-seven patients with GTN who had brain metastases at presentation (25) or developed brain metastases during treatment (12) were treated with multiagent chemotherapy and brain irradiation between 1962 and 2009 (26 prior to 1995 and 11 since 1995). Prior to 1995, all patients received whole-brain irradiation (2400– 4000 cGY in 200–300 cGY fractions); since 1995, patients received whole-brain irradiation (2400–3000 cGY in 200 cGY fractions) +/− stereotactic radiation. No patient received intrathecal chemotherapy. Patient characteristics, including age, preceding pregnancy event, neurologic symptoms, initial hCG, and FIGO score, as well as treatment particulars and disease status were collected and analyzed retrospectively. Results: Of 11 patients with GTN treated for brain metastases from 1995–2009, seven patients (64%) are alive, including six without evidence of disease off treatment. Five of eleven (45%) of these patients developed brain metastases during treatment and 3 (60%) were cured; this contrasts to 6 (23%) of 26 patients who developed brain metastases during treatment from 1962–1994, only 1 (17%) of whom survived. Four of the eleven patients died: one due to noncompliance with chemotherapy, one due to progressive lung metastases, and two from widespread metastatic disease at presentation; none of these patients had uncontrolled brain disease at death. Conclusions: The overall survival for patients with brain metastases in GTN increased from 51% from 1962–1994 to 64% from 1995–2009, including 3 (60%) of 5 patients who developed brain metastases during treatment. All patients who died had widely metastatic disease at presentation. In our experience, brain metastases in GTN are usually curable using a combination of multiagent chemotherapy with high-dose methotrexate and brain irradiation.
191 A multicenter, nonrandomized, open-label, single-arm phase II trial of dovitinib (TKI258) as second-line therapy in patients with fibroblast growth factor receptor 2-mutated or wild-type advanced and/or metastatic endometrial cancer G. Konecny1, N. Finkler2, P. Lee3, A. Yovine4, A. Liu5, P. Sen5, M. Squires4, A. Kay5. 1David Geffen School of Medicine at UCLA, Los Angeles, CA, 2Florida Hospital Cancer Institute, Orlando, FL, 3Duke University Medical Center, Durham, NC, 4Novartis Pharma AG, Basel, Switzerland, 5 Novartis Pharmaceuticals Corporation, East Hanover, NJ. Objective: Advanced or metastatic endometrial carcinoma is typically treated with chemotherapy or hormonal therapy. While many chemotherapy regimens and targeted agents have been evaluated for use as second-line therapies, none has demonstrated durable control of disease. Activating mutations of fibroblast growth factor receptor 2 (FGFR2) have been identified in approximately 10% of endometrial carcinoma tumors, and genetic knockdown or pharmacological blockade of FGFR2 inhibited survival of endometrial carcinoma cells in preclinical models. Dovitinib (TKI258) is an oral investigational agent that inhibits FGFR, vascular endothelial growth factor receptor, and platelet-derived growth factor receptor and has demonstrated antitumor activity in preclinical studies of endometrial carcinoma and other solid tumor models. This multicenter, openlabel, nonrandomized phase II trial is designed to evaluate the safety and efficacy of dovitinib as second-line therapy in patients with advanced and/or metastatic endometrial cancer. Methods: Two groups of patients will be enrolled separately based on the presence (group 1) or absence (group 2) of FGFR2 mutations in tumor samples. Eligible patients must have experienced disease progression after 1 prior line of treatment in the advanced setting. The prior first-line treatment must have included at least 1 cytotoxic agent. Patients will receive dovitinib 500 mg/day on a 5-days-on/2-days-off dosing schedule, until disease progression, unacceptable toxicity, death, or discontinuation due to any other reason. The primary endpoint is progression-free survival (PFS) rate, defined as the percentage of patients who are progression free after 18 weeks of treatment. Secondary endpoints include overall response rate, disease control rate, duration of response, PFS, overall survival, and safety. Efficacy data will be collected and assessed by an external panel of radiologists. The study is designed to enroll patients in 2 stages, with a Bayesian interim monitoring after the first stage. For stage 1, 20 patients will be enrolled in each group. If ≥8 patients in either group with measurable disease at baseline are progression free after 18 weeks of treatment, 20 more patients will be enrolled in that group in stage 2. Results: Preliminary results for each group will be evaluated at the interim analysis. Conclusions: This trial is registered at ClinicalTrials.gov, identifier NCT01379534, and accrual is ongoing.
doi:10.1016/j.ygyno.2011.12.192
192 Brain metastases in gestational trophoblastic neoplasia (GTN): An update N. Neubauer, K. Kalakota, N. Latif, J. Lurain, M. Marymont, W. Small. Northwestern University, Prentice Women's Hospital, Chicago, IL.
doi:10.1016/j.ygyno.2011.12.193
193 Predictors of lymph node metastasis in patients with squamous cell vulvar cancer A. Suri, L. Goodman, M. DiFurio, M. Chiu, J. Soper, L. Van Le. University of North Carolina School of Medicine, Chapel Hill, NC. Objective: Predicting patient population at risk for groin lymph node metastasis may change treatment paradigms for patients with vulvar cancer. The goal of this study was to determine clincopathologic factors associated with lymph node metastasis (LNM) in squamous cell cancer of the vulva. Methods: Retrospective analysis of patients diagnosed with squamous cell vulvar cancer between 1993 and 2010 was conducted. All original pathology slides were reviewed by a gynecologic pathologist to determine peripheral margin distance, deep margin distance, histologic grade, lympho-vascular space invasion (LVSI), depth of invasion (DOI), tumor size, and lymph node status. Tumor characteristics were correlated with LNM using univariable and bivariable logistic Cox regression models.
Objective: Despite the armamentarium of cytotoxic agents in the management of all gynecological cancers, enthusiasm for these agents has been tempered the emergence of resistance. The vascular endothelial factor and the mammalian target of rapamycin (mTOR) have emerged as attractive targets for the design of targeted therapeutics. Investigators have reported alterations in PTEN in gynecological malignancies. The loss of functional PTEN either through deletion, mutation or inactivation leads to the constitutive activation of PI3K effectors in the absence of exogenous stimuli. The frequent loss of PTEN function suggests mTOR inhibition as a rational targeted therapy regulating tumor growth and angiogenesis through VEGF and HIF-1 expression. We conducted a phase I study to evaluate the safety and the therapeutic strategy of targeting the mTOR and VEGF pathway in patients with gynecological malignancies. The objective was to establish a suitable dose for further exploration in a phase II study. Methods: Phase-1 trial using a 3 + 3 step-up dose escalation design. The MTD was defined within one cycle of therapy. 4 dose levels were planned. Dose level 1: Temsirolimus 10 mg IV and Cedarinib 15 mg PO; dose level 2: Temsirolimus 20 mg IV and Cedarinib 15 mg PO; dose level 3: Temsirolimus 20 mg IV and Cedarinib 20 mg PO; dose level 4: Temsirolimus 20 mg IV and Cedarinib 25 mg PO. Results: Study was amended after 2 patients experienced a dose limiting toxicity in cohort 1. Dose limiting toxicities were primarily hematological but also include nonhematological toxicity — namely elevated liver function tests. After IRB approval the study was amended to limit the number of prior lines. Three additional patients were accrued, two patients triggered a DLT as a result of elevated triglycerides. The study was closed to further accrual. Of note four patients experienced SD . One patient with cervical cancer remained stable for 9 months. Conclusions: mTOR is central to gynecological malignancies and represents a pathway that stands at the intersection of multiple important signaling pathways. Tumorgenesis is navigated by redundant pathways. This trial demonstrated that these two pathways may convergence given the increased toxicity observed in cohort 1. Several patients did have stable disease. It is conceivable that the combination of both a mTor inhibitor and a VEGF inhibitor may still hold some value in a selected population.
S79
Objective: Two recent clinical trials evaluating therapeutic HPV vaccines have reported complete responses in excess of 40% of vaccinated subjects with VIN, over a 52-week study window. These trials demonstrate that regression of established high grade intraepithelial lesions can occur in subjects with modest systemic responses detectable after ex vivo stimulation with viral antigens, and that responses “accumulated” over a longer timeframe than is typically used in trial design. We sought to evaluate a novel HPV16E7 vaccine in patients with CIN3. Methods: A phase I trial is being conducted testing intradermal, intracervical, and intramuscular routes of administration of a DNA vaccine targeting HPV16E7, in subjects with HPV16 + CIN3, prior to LEEP 8 weeks post-vaccination. Clinical trial endpoints include assessment of regression of CIN, and immune response. Results: To date, 9 patients have been enrolled onto 2 dose cohorts (intradermal administration). No significant vaccine-associated toxicity has been noted. Although no complete regressions have occurred, interim within-subject analyses of tissue specimens from the first dose cohort demonstrate an increase in cervical CD8+ infiltrates preand post-vaccination, resulting in an increased ratio of CD8:Treg cells. The density of Tbet+ infiltrates increased an average of 4.6-fold in lesional epithelium and by 7.6-fold in lesional stroma. The distribution of Tregs was greater in lesional stroma compared to epithelium at both timepoints. Conclusions: As expected, the DNA vaccine administered intradermally is well tolerated. Increased densities of Tbet+ cells in both the stromal and epithelial compartment of cervical mucosa suggest the generation of type I immunity. The distribution of Tregs suggests that the stromal compartment may play a role in conditioning immune responses in persistent mucosal HPV infections. Accrual to this trial is ongoing. Supported by NCI P50CA098252, NIH CTSA UL1RR025005, the Dana Foundation, NCI R21CA128232, NCI R01CA142691, and NCI P30CA006973.
doi:10.1016/j.ygyno.2011.12.190
Clinical Trials - Uterine Cancer/Endometrial/Sarcoma, Phase II/III Toxicity
G1
G2
G3
G4
Heme Non heme Nervous Cardiac Renal ID GI Endocrine Metabolic Constitutional Pain Muscle Pulmonary Derm
12
3
2
0
8 1 1 0 31 0 23 10 7 0 5 10
1 6 3 4 9 1 6 6 2 1 0 0
0 3 0 0 1 0 3 0 1 0 1 0
0 0 0 0 0 0 0 0 0 0 1 0
doi:10.1016/j.ygyno.2011.12.189
189 Location, location, location: Immune responses in patients with CIN3 receiving therapeutic HPV16E7 vaccination C. Trimble1, C. Hung1, S. Peng1, T. Wu1, W. Huh2, E. Partridge2, L. Maldonado1, N. Barat1, R. Alvarez2. 1Johns Hopkins Medical Institutions, Baltimore, MD, 2University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham, AL.
190 Treatment of women with intermediate risk endometrial cancer J. Geisler, T. Harvey, G. Phibbs, K. Manahan. University of Toledo Medical Center, Toledo, OH. Objective: Randomized trials have sought to analyze the survival differences among treatment strategies for women with intermediate risk stage I endometrial cancer (IREC) after total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAHBSO) with or without pelvic and para-aortic lymph node dissection (LND).We sought to evaluate the cost effectiveness of these strategies. Methods: A decision model was developed based on Gynecologic Oncology Group (GOG) protocol 99 along with the ASTEC and PORTEC studies. Regimen 1 is TAHBSO with radiation therapy (XRT) (TAHBSO XRT). Regimen 2 is TAHBSO LND. Regimen 3 is TAHBSO LND with XRT for intermediate risks. Cost effectiveness analysis (CEA) was performed using data from Medicare and published studies incorporating costs, complications, recurrence rates, complications, and survival. Incremental cost to effectiveness ratios (IC/IE) was determined by any nondominated treatment options. Sensitivity analyses were performed. Results: The average cost per patient for TAHBSO LND XRT was $26,142; TAHBSO XRT was $24,942; and TAHBSO LND was $7187. TAHBSO XRT had both increased cost and decreased effectiveness compared to TAHBSO LND. The IC/IE between TAHBSO LND XRT and TAHBSO LND was $2,367,243 per percentage of 5 year survival. Although TAHBSO XRT was
S80
Abstracts / Gynecologic Oncology 125 (2012) S3–S167
dominated in analysis, a one-way sensitivity analysis was performed for comparison demonstrating that 5 year survival would have to be greater than 100% for TAHBSO XRT to be cost effective. Conclusions: Performing TAHBSO LND without radiation for IREC is the most cost effective treatment; therefore, TAHBSO XRT should not be recommended as treatment.
GTD/Vulvar & Vaginal Cancers/Rare Tumors
doi:10.1016/j.ygyno.2011.12.191
Objective: To update the treatment of brain metastases in GTN at our center comparing treatment and outcomes from 1962 to 1994 (Radiology 196; 200: 277–280) with those from 1995 to 2009. Methods: Thirty-seven patients with GTN who had brain metastases at presentation (25) or developed brain metastases during treatment (12) were treated with multiagent chemotherapy and brain irradiation between 1962 and 2009 (26 prior to 1995 and 11 since 1995). Prior to 1995, all patients received whole-brain irradiation (2400– 4000 cGY in 200–300 cGY fractions); since 1995, patients received whole-brain irradiation (2400–3000 cGY in 200 cGY fractions) +/− stereotactic radiation. No patient received intrathecal chemotherapy. Patient characteristics, including age, preceding pregnancy event, neurologic symptoms, initial hCG, and FIGO score, as well as treatment particulars and disease status were collected and analyzed retrospectively. Results: Of 11 patients with GTN treated for brain metastases from 1995–2009, seven patients (64%) are alive, including six without evidence of disease off treatment. Five of eleven (45%) of these patients developed brain metastases during treatment and 3 (60%) were cured; this contrasts to 6 (23%) of 26 patients who developed brain metastases during treatment from 1962–1994, only 1 (17%) of whom survived. Four of the eleven patients died: one due to noncompliance with chemotherapy, one due to progressive lung metastases, and two from widespread metastatic disease at presentation; none of these patients had uncontrolled brain disease at death. Conclusions: The overall survival for patients with brain metastases in GTN increased from 51% from 1962–1994 to 64% from 1995–2009, including 3 (60%) of 5 patients who developed brain metastases during treatment. All patients who died had widely metastatic disease at presentation. In our experience, brain metastases in GTN are usually curable using a combination of multiagent chemotherapy with high-dose methotrexate and brain irradiation.
191 A multicenter, nonrandomized, open-label, single-arm phase II trial of dovitinib (TKI258) as second-line therapy in patients with fibroblast growth factor receptor 2-mutated or wild-type advanced and/or metastatic endometrial cancer G. Konecny1, N. Finkler2, P. Lee3, A. Yovine4, A. Liu5, P. Sen5, M. Squires4, A. Kay5. 1David Geffen School of Medicine at UCLA, Los Angeles, CA, 2Florida Hospital Cancer Institute, Orlando, FL, 3Duke University Medical Center, Durham, NC, 4Novartis Pharma AG, Basel, Switzerland, 5 Novartis Pharmaceuticals Corporation, East Hanover, NJ. Objective: Advanced or metastatic endometrial carcinoma is typically treated with chemotherapy or hormonal therapy. While many chemotherapy regimens and targeted agents have been evaluated for use as second-line therapies, none has demonstrated durable control of disease. Activating mutations of fibroblast growth factor receptor 2 (FGFR2) have been identified in approximately 10% of endometrial carcinoma tumors, and genetic knockdown or pharmacological blockade of FGFR2 inhibited survival of endometrial carcinoma cells in preclinical models. Dovitinib (TKI258) is an oral investigational agent that inhibits FGFR, vascular endothelial growth factor receptor, and platelet-derived growth factor receptor and has demonstrated antitumor activity in preclinical studies of endometrial carcinoma and other solid tumor models. This multicenter, openlabel, nonrandomized phase II trial is designed to evaluate the safety and efficacy of dovitinib as second-line therapy in patients with advanced and/or metastatic endometrial cancer. Methods: Two groups of patients will be enrolled separately based on the presence (group 1) or absence (group 2) of FGFR2 mutations in tumor samples. Eligible patients must have experienced disease progression after 1 prior line of treatment in the advanced setting. The prior first-line treatment must have included at least 1 cytotoxic agent. Patients will receive dovitinib 500 mg/day on a 5-days-on/2-days-off dosing schedule, until disease progression, unacceptable toxicity, death, or discontinuation due to any other reason. The primary endpoint is progression-free survival (PFS) rate, defined as the percentage of patients who are progression free after 18 weeks of treatment. Secondary endpoints include overall response rate, disease control rate, duration of response, PFS, overall survival, and safety. Efficacy data will be collected and assessed by an external panel of radiologists. The study is designed to enroll patients in 2 stages, with a Bayesian interim monitoring after the first stage. For stage 1, 20 patients will be enrolled in each group. If ≥8 patients in either group with measurable disease at baseline are progression free after 18 weeks of treatment, 20 more patients will be enrolled in that group in stage 2. Results: Preliminary results for each group will be evaluated at the interim analysis. Conclusions: This trial is registered at ClinicalTrials.gov, identifier NCT01379534, and accrual is ongoing.
doi:10.1016/j.ygyno.2011.12.192
192 Brain metastases in gestational trophoblastic neoplasia (GTN): An update N. Neubauer, K. Kalakota, N. Latif, J. Lurain, M. Marymont, W. Small. Northwestern University, Prentice Women's Hospital, Chicago, IL.
doi:10.1016/j.ygyno.2011.12.193
193 Predictors of lymph node metastasis in patients with squamous cell vulvar cancer A. Suri, L. Goodman, M. DiFurio, M. Chiu, J. Soper, L. Van Le. University of North Carolina School of Medicine, Chapel Hill, NC. Objective: Predicting patient population at risk for groin lymph node metastasis may change treatment paradigms for patients with vulvar cancer. The goal of this study was to determine clincopathologic factors associated with lymph node metastasis (LNM) in squamous cell cancer of the vulva. Methods: Retrospective analysis of patients diagnosed with squamous cell vulvar cancer between 1993 and 2010 was conducted. All original pathology slides were reviewed by a gynecologic pathologist to determine peripheral margin distance, deep margin distance, histologic grade, lympho-vascular space invasion (LVSI), depth of invasion (DOI), tumor size, and lymph node status. Tumor characteristics were correlated with LNM using univariable and bivariable logistic Cox regression models.