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Supplemental Figure 1. Correlation between dermal mitotic rate and patient survival. Kaplan-Meier estimate of (A) overall survival and (B) disease-specific survival based on dermal mitotic rate (mitotic figures/mm2). Supplemental Figure 2. Derivation of proposed T-category for Primary Vulvar Melanoma. (A, B, C) We first assigned patients with PVM to a T-category according to the AJCC for PCM (7th Edition). (A) Shows the AJCC schema and the number of patients assigned to each category. (B) Kaplan Meier DSS curves for patients stratified by AJCC T-categories demonstrate robust prognostic differences for patients with PVM and pT1 and to an extent pT2 disease from those with pT3 and pT4 disease, but less robust stratification among those patients with PVMs {less than or equal to}2.00 mm; pT1 versus pT2 (isolated in C) or >2.0 mm; pT3 and pT4. (D, E, F) Because both tumor thickness and mitotic rate were independent prognostic factors for DSS and because mitotic rate showed a natural prognostic separation at 2 mitotic figures/mm2 (as shown in Figure 1D), we first asked whether a T-category according to the conventional AJCC cut-offs ({less than or equal to}1.0, 1.01-2.0, 2.01-4.0 and >4.0 mm) subsequently modified by mitotic rate (a: 2.0 mm (pT3 and pT4) had a short DSS independent of mitotic rate. More importantly, among patients with a tumor thickness {less than or equal to}2.0 mm (pT1 or pT2), only those with mitotic rate {greater than or equal to}2/mm2 had a short DSS, which was essentially superimposable with patients with pT3 and pT4 PVM in this schema. (F) Kaplan-Meier survival curve for patients with pT1 and pT2 PVMs show striking differences in survival according to mitotic rate (

Kaplan-Meier estimate of (A) overall survival and (B) disease-specific survival based on dermal mitotic rate (mitotic figures/mm2).

Purpose: Primary vulvar melanoma (PVM) is the second most common vulvar malignancy. Despite their distinct anatomic site and unique molecular–genetic alterations, PVMs are staged according to the American Joint Committee on Cancer (AJCC) guidelines for primary cutaneous melanomas (PCM). However, whether parameters derived for PCM also apply to PVM remain a critical yet largely unexplored clinical question. The objective of this study was to determine the parameters predictive of survival in PVM.Experimental Design: We retrospectively reviewed 100 patients with PVM and determined associations between clinical and histopathologic parameters and disease-specific survival (DSS) and overall survival (OS).Results: Univariate Cox regression analysis demonstrated older age (>56 years), greater tumor thickness, higher dermal mitotic rate, ulceration, lymphovascular invasion, perineural invasion, microscopic satellitosis, and absence of precursor nevus associated with decreased OS. Furthermore, age, midline, and/or multifocal involvement, greater tumor thickness, higher dermal mitotic rate, ulceration, lack of regression, lymphovascular invasion, perineural invasion, and microscopic satellitosis associated with decreased DSS. Multivariate analysis demonstrated tumor thickness, dermal mitotic rate, lymphovascular invasion, microscopic satellitosis, and absence of precursor nevus independently predicted shorter OS. Only tumor thickness and increased dermal mitotic rate (≥2/mm2) independently predicted reduced DSS. In comparison with the AJCC T-category, a novel, bivariate T-category based only on tumor thickness and dermal mitotic rate robustly predicted OS and DSS in our patient cohort.Conclusions: In the largest single institutional study of PVM, we demonstrate a combination of tumor thickness and mitotic rate comprise a simple but robust T-category to direct staging and prognosis. Clin Cancer Res; 23(8); 2093–104. ©2016 AACR.

TT, tumor thickness; NR, not reported * Includes vulvar (n=14) and vaginal (n=7) melanomas £ Includes vulvar (n=16), vaginal (n=1) and cervical (n=1) melanomas Â¥ Includes vulvar (n=61), vaginal (n=15), urethral (n=5) and cervical (n=4) melanomas Â,¬ Includes vulvar (n=33) and vaginal (n=11) melanomas Î' Includes vulvar (n=58), vaginal (n=11), cervical (n=7) and other (n=9) melanomas

(A, B, C) We first assigned patients with PVM to a T-category according to the AJCC for PCM (7th Edition). (A) Shows the AJCC schema and the number of patients assigned to each category. (B) Kaplan Meier DSS curves for patients stratified by AJCC T-categories demonstrate robust prognostic differences for patients with PVM and pT1 and to an extent pT2 disease from those with pT3 and pT4 disease, but less robust stratification among those patients with PVMs {less than or equal to}2.00 mm; pT1 versus pT2 (isolated in C) or >2.0 mm; pT3 and pT4. (D, E, F) Because both tumor thickness and mitotic rate were independent prognostic factors for DSS and because mitotic rate showed a natural prognostic separation at 2 mitotic figures/mm2 (as shown in Figure 1D), we first asked whether a T-category according to the conventional AJCC cut-offs ({less than or equal to}1.0, 1.01-2.0, 2.01-4.0 and >4.0 mm) subsequently modified by mitotic rate (a: 2.0 mm (pT3 and pT4) had a short DSS independent of mitotic rate. More importantly, among patients with a tumor thickness {less than or equal to}2.0 mm (pT1 or pT2), only those with mitotic rate {greater than or equal to}2/mm2 had a short DSS, which was essentially superimposable with patients with pT3 and pT4 PVM in this schema. (F) Kaplan-Meier survival curve for patients with pT1 and pT2 PVMs show striking differences in survival according to mitotic rate (

M1a, Metastasis in skin, subcutaneous tissues, or distant lymph nodes; M1b, Metastasis to lung; M1c, Metastasis to all other visceral sites.

PURPOSE The Groningen International Study on Sentinel nodes in Vulvar cancer (GROINSS-V)-II investigated whether inguinofemoral radiotherapy is a safe alternative to inguinofemoral lymphadenectomy (IFL) in vulvar cancer patients with a metastatic sentinel node (SN). METHODS GROINSS-V-II was a prospective multicenter phase-II single-arm treatment trial, including patients with early-stage vulvar cancer (diameter < 4 cm) without signs of lymph node involvement at imaging, who had primary surgical treatment (local excision with SN biopsy). Where the SN was involved (metastasis of any size), inguinofemoral radiotherapy was given (50 Gy). The primary end point was isolated groin recurrence rate at 24 months. Stopping rules were defined for the occurrence of groin recurrences. RESULTS From December 2005 until October 2016, 1,535 eligible patients were registered. The SN showed metastasis in 322 (21.0%) patients. In June 2010, with 91 SN-positive patients included, the stopping rule was activated because the isolated groin recurrence rate in this group went above our predefined threshold. Among 10 patients with an isolated groin recurrence, nine had SN metastases > 2 mm and/or extracapsular spread. The protocol was amended so that those with SN macrometastases (> 2 mm) underwent standard of care (IFL), whereas patients with SN micrometastases (≤ 2 mm) continued to receive inguinofemoral radiotherapy. Among 160 patients with SN micrometastases, 126 received inguinofemoral radiotherapy, with an ipsilateral isolated groin recurrence rate at 2 years of 1.6%. Among 162 patients with SN macrometastases, the isolated groin recurrence rate at 2 years was 22% in those who underwent radiotherapy, and 6.9% in those who underwent IFL ( P = .011). Treatment-related morbidity after radiotherapy was less frequent compared with IFL. CONCLUSION Inguinofemoral radiotherapy is a safe alternative for IFL in patients with SN micrometastases, with minimal morbidity. For patients with SN macrometastasis, radiotherapy with a total dose of 50 Gy resulted in more isolated groin recurrences compared with IFL.

Introduction50–70% of epithelial ovarian cancers overexpress epidermal growth factor receptor, and its expression has been correlated with poor prognosis. We conducted a phase Ib/II trial to examine the efficacy, safety, and toxicity of gefitinib, a tyrosine kinase inhibitor, combined with topotecan in women with recurrent ovarian cancer with epidermal growth factor receptor positivity.MethodsPatients with measurable recurrent or persistent cancer after treatment with a platinum containing regimen with positive epidermal growth factor receptor expression, as determined by immunohistochemistry, were eligible for the study. Initial treatment was 250 mg/day gefitinib (oral) and 2.0 mg/m2 topotecan (intravenous) on days 1, 8, and 15, on a 28 day cycle. Dose escalations were planned for topotecan (dose levels 1–3: 2, 3, and 4 mg/m2) until the maximum tolerated dose was reached.Results19 patients received a total of 61 cycles. Median age was 59.8 years (range 42–76 years). Histologic types in treated patients included 74% serous (n=14), 11% mixed (n=2), 11% transitional (n=2), and 5% clear cell (n=1). For phase Ib, three patients were treated at dose level 1, three at dose level 2, and three at dose level 3 for topotecan. The maximum tolerated dose was 4.0 mg/m2 (days 1, 8, and 15) for topotecan and 250 mg (daily) for gefitinib. Therefore, dose level 3 was used for phase II. Among the 19 patients, 63.2% (n=12) had progressive disease, 15.8% (n=3) had stable disease, 10.5% (n=2) had a partial response, and 10.5% (n=2) were not evaluable. The most serious adverse events of any grade attributed to the therapy were anemia (89.4%), neutropenia (68.4%), abdominal pain (84%), constipation (78.9%), and diarrhea (78.9%).ConclusionAlthough the drug combination was relatively well tolerated, this prospective phase Ib/II clinical trial did not show sufficient clinical activity of topotecan combined with gefitinib in patients with epidermal growth factor receptor positive recurrent ovarian, fallopian tube, or peritoneal cancers.

To review efficiency metrics and patient safety data before and after implementation of a structured review process for surgical innovations.Surgical innovation ranges from minor incremental improvement to radical experimentation. Although innovation paradigms have been described, these are not widely adopted or enforced in the surgical community.A Continuous Quality Improvement Team (CQIT) of surgical quality officers and perioperative nurses was organized to perform structured reviews of proposed new surgical devices and procedures at a large quaternary cancer care center. The CQIT process was placed to precede an established Value Analysis Team business evaluation. Pre- and post-CQIT implementation metrics of approval process efficiency and patient safety data were compared. Seven novel procedures were also vetted by the CQIT.Forty-six product requests were evaluated after CQIT implementation. Compared with 34 products evaluated prior to CQIT establishment, the total mean evaluation time decreased from 124 to 51 days (P= 0.007). For new devices requiring intraoperative trial, the time between product proposal and trial decreased from a mean of 260 to 99 days (P= 0.014). The rate of device-related complications in the pre-CQIT group was 10% compared with 0% post-CQIT. Two devices, which administratively bypassed CQIT review, had both minor and major complications, including a mortality. Five novel procedures approved by CQIT with simulation were performed without complications.Using novel algorithms, the addition of a dedicated team of surgical quality officers to the surgical innovation evaluation process improved both the efficiency and the safety associated with introducing new devices and procedures into practice.

Objective Up to 87% of uterine leiomyosarcomas have estrogen receptor positivity. There are no effective adjuvant therapies for LMS. The objective of this study was to determine the efficacy of letrozole in patients with newly diagnosed uterine leiomyosarcoma (uLMS). The primary endpoint of this study was a reduction in the recurrence rate for patients with this disease. Methods We performed a randomized, open-label, phase II study of letrozole (experimental arm) administered orally on a daily basis vs. observation (control) in patients with newly diagnosed early stage uLMS. Patient enrollment was to be open to any individual with newly diagnosed uLMS seen in the Gynecologic Oncology Center at M. D. Anderson Cancer Center. Hormone receptor positivity using CLIA approved lab testing was an eligibility requirement. No prior therapy was allowed. Results Nine patients were randomized. Four patients were in the experimental arm and five patients were in the observation arm. No patients had prior therapy. The median duration of protocol treatment was 43.9 months (range, 6.5–70.2). The median PFS for the experimental arm was not reached (NR) compared to 17.3 months. The percent progression free at 12 and 24 months was 100% for patients receiving letrozole compared to 80% at 12 months and 40% at 24 months for patients in the observation arm. Conclusions While no definitive conclusions can be made due to early study closure, these early observations warrant further investigation. We desperately need an effective adjuvant therapy for women with early stage uLMS., Highlights • Adjuvant therapy for patients with early stage uterine leiomyosarcoma (uLMS) represents an unmet medical need. • We hypothesized that hormonal manipulation can positively impact survival in this group of patients. • Results suggest aromatase inhibitor therapy may be an active agent in early stage uterine leiomyosarcoma. • Low accrual due to rare disease type resulted in early study closure.

BackgroundRadiographic triage measures in patients with new advanced ovarian cancer have yielded inconsistent results.ObjectiveTo determine the correlation between surgeon radiology assessment and laparoscopic scoring by disease sites in patients with newly diagnosed advanced stage ovarian cancer.MethodsFourteen gynecologic oncology surgeons from a single institution performed a blinded review of pre-operative contrast-enhanced CT imaging from patients with advanced stage ovarian cancer. Each of the patients had also undergone laparoscopic scoring assessment, between April 2013 and December 2017, to determine primary resectability using the validated Fagotti scoring method, and assigned a predictive index value score. Surgeons were asked to provide expected predictive index value scores based on their blinded review of the antecedent CT imaging. Linear mixed models were conducted to calculate the correlation between radiologic and laparoscopic score for surgeons individually, and as a group. Once the model was fit, the inter-class correlation and 95% CI were calculated.ResultsRadiology review was performed on 20 patients with advanced stage ovarian cancer who underwent laparoscopic scoring assessment. Surgeon faculty rank included assistant professor (n=5), associate professor (p=4), and professor (n=5). The kappa inter-rater agreement was −0.017 (95% CI −0.023 to −0.005), indicating low inter-rater agreement between radiology review and actual laparoscopic score. The inter-class correlation in this model was 0.06 (0.02–0.21), indicating that surgeons do not score the same across all the images. When using a clinical cut-off point for the predictive index value of 8, the probability of agreement between radiology and actual laparoscopic score was 0.56 (95% CI 0.49 to 0.73). Examination of disease site sub-scales showed that the probability of agreement was as follows: peritoneum 0.57 (95% CI 0.51 to 0.62), diaphragm 0.54 (95% CI 0.48 to 0.60), mesentery 0.51 (95% CI 0.45 to 0.57), omentum 0.61 (95% CI 0.55 to 0.67), bowel 0.54 (95% CI 0.44 to 0.64), stomach 0.71 (95% CI 0.65 to 0.76), and liver 0.36 (95% CI 0.31 to 0.42). The number of laparoscopic scoring cases, tumor reductive surgery cases, or faculty rank was not significantly associated with overall or sub-scale agreement.ConclusionsSurgeon radiology review did not correlate highly with actual laparoscopic scoring assessment findings in patients with advanced stage ovarian cancer. Our study highlights the limited accuracy of surgeon radiographic assessment to determine resectability.

Introduction/Background Introduction: GROINSS-V II investigated whether radiotherapy is a safe alternative for inguinofemoral lymphadenectomy (IFL) in vulvar cancer patients with a metastatic sentinel node (SN). Methodology Methods: In GROINSS-V II, a prospective multicentre phase II trial, patients were included with early-stage squamous cell carcinoma (SCC) of the vulva (diameter Results From December 2005 until October 2016, 1552 eligible patients were registered. SN-metastasis occurred in 324/1552 (21%) patients. After 54 months of inclusion the stopping-rule for SN-positive patients was activated; interim analysis showed an increased risk for groin recurrence in case of SN-metastasis >2 mm and/or extranodal extension (ENE). After amendment of the protocol only patients with SN-micrometastasis ≤2 mm received radiotherapy, while those with SN metastasis >2 mm underwent IFL (with radiotherapy if >1 metastasis or ENE). Final analysis after ≥2 years of follow-up revealed six isolated groin recurrences in 157 patients with a SN-micrometastasis (3.8%). Four could not be considered radiotherapy failures: two developed recurrence in the contralateral (SN-negative) groin, two refused radiotherapy. Twenty-eight patients did not get radiotherapy (2 recurrences;7.1%). Among 129 patients who received radiotherapy to the groin(s) only two isolated groin recurrences were diagnosed (1.6%: 95%CI:0–3.8%). The combination of radiotherapy with SN was associated with minimal toxicity: 5/118(4.2%) grade 3 toxicity, no grade 4 or 5 toxicity. In 38/1222 SN-negative patients (3.1%: 95%CI:2.1–4.1%) isolated groin recurrences were diagnosed with clear protocol violations in 6 patients: incomplete treatment of the groin (n=3); primary tumor >4cm (n=1); not all SNs visualized on the lymphoscintigram removed (n=2). After exclusion of these protocol violations an isolated groin recurrence rate of 2.6% (95%CI:1.7–3.5%) was observed. Conclusion Radiotherapy to the groins is a safe alternative for IFL in patients with SN metastasis ≤2 mm, with minimal toxicity. We further established the safety of omitting IFL in patients with SCC of the vulva 2 mm, radiotherapy with a total dose of 50Gy was no safe alternative for IFL; dose escalation and/or chemoradiation should be investigated in these patients. Disclosure Funded by Dutch Cancer Society.

It is 25 years since sentinel lymph node biopsy was introduced into the care of women with vulvar cancer.[1][1] Congratulations to Moloney and co-authors for taking an analytic approach to standardizing sentinel lymph node biopsy in the management of endometrial cancer.[2][2] They enrolled credible

5505 Background: Wee1 phosphorylates and inhibits cyclin-dependent kinases 1 and 2 and is involved in regulation of the intra-S and G2/M cell cycle checkpoint arrest for premitotic DNA repair. The Wee1 inhibitor, adavosertib, has demonstrated activity alone and in combination with olaparib in PARP inhibitor (PARPi)-resistant preclinical models. We sought to evaluate efficacy of adavosertib (A) with or without olaparib (O) in a phase II noncomparative study of recurrent PARPi-resistant ovarian cancer. Methods: Women with recurrent ovarian, fallopian tube or primary peritoneal cancer with documented progressive disease on a PARPi were eligible. All patients (pts) had measurable disease and adequate end organ function. On the A arm, pts received A 300mg PO daily on days 1-5 and 8-12 of a 21-day cycle. On the A/O arm, pts received A 150mg PO BID on days 1-3 and 8-10 and O 200mg PO BID on days 1-21 of a 21-day cycle. Primary endpoint was objective response per RECIST 1.1 and was assessed every 2 cycles. Clinical benefit rate (CBR) was defined as proportion of pts with objective response or stable disease > 16 weeks. Progression free survival (PFS) was assessed using the Kaplan Meier method and calculated from date of treatment initiation to earliest date of progression, death, or last visit. Results: 116 pts were screened with 80 pts enrolled and randomized (A: n=39, A/O: n=41). Median age was 60 years (range 36-76) and the majority of pts had platinum resistant disease (64%) and high grade serous histology (98%). Pts received a median of 4 prior therapies (range 1-11) and 48% had germline or somatic BRCA mutations. There were 35 pts evaluable for response in each arm. Table demonstrates efficacy data. On the A arm, Grade 3/4 toxicities occurred in 51% of pts, most commonly neutropenia (13%), thrombocytopenia (10%), and diarrhea (8%). 28 (72%) pts required at least one dose interruption and 20 (51%) required dose reduction. On the A/O arm, Grade 3/4 toxicities occurred in 76% of pts, most commonly thrombocytopenia (20%), neutropenia (15%), diarrhea (12%), fatigue (12%), and anemia (10%). 36 (88%) of pts required at least one dose interruption, 29 (71%) required dose reduction, and 4 (10%) did not restart due to toxicity. Conclusions: A given alone and in combination with O demonstrated efficacy in pts with PARPi-resistant ovarian cancer. Although grade 3 and 4 toxicities were observed on both arms, these were generally manageable with supportive care, dose interruptions and dose reductions as needed. Additional translational analyses are ongoing to clarify which pts received clinical benefit. Clinical trial information: NCT03579316. [Table: see text]

Sentinel lymph node (SLN) mapping continues to evolve in the surgical staging of endometrial cancer (EC). The purpose of this trial was to identify the sensitivity, false negative rate (FNR) and FN predictive value (FNPV) of SLN compared to complete pelvic and para-aortic lymphadenectomy (LAD) in women with high-risk EC.Women with high-risk EC (grade 3, serous, clear cell, carcinosarcoma) were enrolled in this prospective surgical trial. All patients underwent preoperative PET/CT and intraoperative SLN biopsy followed by LAD. Patients with peritoneal disease on imaging or at the time of surgery were excluded. Patients were evaluable if SLN was attempted and complete LAD was performed.123 patients were enrolled between 4/13 and 5/16; 101 were evaluable. At least 1 SLN was identified in 89% (90); bilateral detection 58%, unilateral pelvic 40%, para-aortic only 2%. Indocyanine green was used in 61%, blue dye in 28%, and blue dye and technetium in 11%. Twenty-three pts. (23%) had ≥1 positive node. In 20/23, ≥1 SLN was identified and in 19/20 the SLN was positive. Only 1 patient had bilateral negative SLN and positive non-SLNs on final pathology. Overall, sensitivity of SLN was 95% (19/20), FNR was 5% (1/20) and FNPV was 1.4% (1/71). If side-specific LAD was performed when a SLN was not detected, the FNR decreased to 4.3% (1/23).This prospective trial demonstrated that SLN biopsy plus side-specific LAD, when SLN is not detected, is a reasonable alternative to a complete LAD in high-risk endometrial cancer.

Purpose: Primary vulvar melanoma (PVM) is the second most common vulvar malignancy. Despite their distinct anatomic site and unique molecular–genetic alterations, PVMs are staged according to the American Joint Committee on Cancer (AJCC) guidelines for primary cutaneous melanomas (PCM). However, whether parameters derived for PCM also apply to PVM remain a critical yet largely unexplored clinical question. The objective of this study was to determine the parameters predictive of survival in PVM. Experimental Design: We retrospectively reviewed 100 patients with PVM and determined associations between clinical and histopathologic parameters and disease-specific survival (DSS) and overall survival (OS). Results: Univariate Cox regression analysis demonstrated older age (>56 years), greater tumor thickness, higher dermal mitotic rate, ulceration, lymphovascular invasion, perineural invasion, microscopic satellitosis, and absence of precursor nevus associated with decreased OS. Furthermore, age, midline, and/or multifocal involvement, greater tumor thickness, higher dermal mitotic rate, ulceration, lack of regression, lymphovascular invasion, perineural invasion, and microscopic satellitosis associated with decreased DSS. Multivariate analysis demonstrated tumor thickness, dermal mitotic rate, lymphovascular invasion, microscopic satellitosis, and absence of precursor nevus independently predicted shorter OS. Only tumor thickness and increased dermal mitotic rate (≥2/mm2) independently predicted reduced DSS. In comparison with the AJCC T-category, a novel, bivariate T-category based only on tumor thickness and dermal mitotic rate robustly predicted OS and DSS in our patient cohort. Conclusions: In the largest single institutional study of PVM, we demonstrate a combination of tumor thickness and mitotic rate comprise a simple but robust T-category to direct staging and prognosis. Clin Cancer Res; 23(8); 2093–104. ©2016 AACR.

Purpose In 2010, a randomized clinical trial demonstrated noninferior survival for patients with advanced ovarian cancer who were treated with neoadjuvant chemotherapy (NACT) compared with primary cytoreductive surgery (PCS). We examined the use and effectiveness of NACT in clinical practice. Patients and Methods A multi-institutional observational study of 1,538 women with stages IIIC to IV ovarian cancer who were treated at six National Cancer Institute–designated cancer centers. We examined NACT use in patients who were diagnosed between 2003 and 2012 (N = 1,538) and compared overall survival (OS), morbidity, and postoperative residual disease in a propensity-score matched sample of patients (N = 594). Results NACT use increased from 16% during 2003 to 2010 to 34% during 2011 to 2012 in stage IIIC disease ( Ptrend < .001), and from 41% to 62% in stage IV disease ( Ptrend < .001). Adoption of NACT varied by institution, from 8% to 30% for stage IIIC disease (P < .001) and from 27% to 61% ( P = .007) for stage IV disease during this time period. In the matched sample, NACT was associated with shorter OS in stage IIIC disease (median OS: 33 v 43 months; hazard ratio [HR], 1.40; 95% CI, 1.11 to 1.77) compared with PCS, but not stage IV disease (median OS: 31 v 36 months; HR, 1.16; 95% CI, 0.89 to 1.52). Patients with stages IIIC and IV disease who received NACT were less likely to have ≥ 1 cm postoperative residual disease, an intensive care unit admission, or a rehospitalization (all P ≤ .04) compared with those who received PCS treatment. However, among women with stage IIIC disease who achieved microscopic or ≤ 1 cm postoperative residual disease, NACT was associated with decreased OS (HR, 1.49; 95% CI, 1.01 to 2.18; P = .04). Conclusion Use of NACT increased significantly between 2003 and 2012. In this observational study, PCS was associated with increased survival in stage IIIC, but not stage IV disease. Future studies should prospectively consider the efficacy of NACT by extent of residual disease in unselected patients.

Background Postoperative urinary tract infection (UTI) is a frequent complication that diminishes patient experience and incurs substantial costs. The purpose of this project was to develop a urinary tract care assessment tool that would lead to actionable quality improvement initiatives. Methods Multidisciplinary teams at a single institution developed the S.T.O.P. UTI algorithm to assess elements related to urinary catheter care: Sterile catheter placement, Timely catheter removal, Optimal collection bag position, and Proper urine sampling for urinalysis and culture. Based on this evaluation, a targeted intervention was applied to address deficient areas in surgical patients. UTI rates were monitored. Results The assessment revealed that best practice for sterile placement was being performed but that time to removal, optimal positioning, and proper sampling could be improved. Providers were educated on best practice for catheter removal, nurses placed a reminder note on the chart, personnel were taught about optimal catheter positioning, and nursing assistants were educated on best practices for collection of urine. From 2012 to 2015, non-risk-adjusted UTI rates in surgical patients decreased from 2.90% to 0.46% (p = 0.0003), and the American College of Surgeons National Surgical Quality Improvement Program risk-adjusted comparison improved from the 8th to the 4th decile. Simultaneously, hospitalwide catheter-associated UTI rates also decreased, from 2.24/1,000 catheter-days in 2014 to 0.70/1,000 catheter-days in 2016 (p Conclusion The S.T.O.P. UTI algorithm is a tool that hospitals can use to systematically assess UTI processes. The program can identify areas for improvement specific to an institution, directing the allocation of quality improvement resources to decrease both surgical and medical UTIs.

Purpose: Surgical site infections (SSIs) are associated with patient morbidity and increased health care costs. Although several national organizations including the University HealthSystem Consortium (UHC), the National Surgical Quality Improvement Program (NSQIP), and the National Healthcare Safety Network (NHSN) monitor SSI, there is no standard reporting methodology. Methods: We queried the UHC, NSQIP, and NHSN databases from July 2012 to June 2014 for SSI after gynecologic surgery at our institution. Each organization uses different definitions and inclusion and exclusion criteria for SSI. The rate of SSI was also obtained from chart review from April 1 to June 30, 2014. SSI was classified as superficial, deep, or organ space infection. The rates reported by the agencies were compared with the rates obtained by chart review using Fisher’s exact test. Results: Overall SSI rates for the databases were as follows: UHC, 1.5%; NSQIP, 8.8%; and NHSN, 2.8% (P < .001). The individual databases had wide variation in the rate of deep infection (UHC, 0.7%; NSQIP, 4.7%; NHSN, 1.3%; P < .001) and organ space infection (UHC, 0.4%; NSQIP, 4.4%; NHSN, 1.4%; P < .001). In agreement with the variation in reporting methodology, only 19 cases (24.4%) were included in more than one database and only one case was included in all three databases (1.3%). Conclusion: There is discordance among national reporting agencies tracking SSI. Adopting standardized metrics across agencies could improve consistency and accuracy in assessing SSI rates.

Objective Shared medical appointments offer a novel approach to improve efficiency and quality of care consistent with the goals of the Institute of Medicine. Our objective was to develop and implement a shared medical appointment for gynecologic cancer patients initiating chemotherapy. Methods We first assessed the level of interest in shared medical appointments among our patients and providers through qualitative interviews. Both patients and providers identified pre-chemotherapy as an optimal area to pilot shared medical appointments. We subsequently created a multidisciplinary team comprised of physicians, advanced practice providers, nurses, pharmacists, administrators, health education specialists and members of the Quality Improvement Department to establish a Shared Medical Appointment and Readiness Teaching (SMART) program for all gynecologic oncology patients initiating chemotherapy with platinum- and/or taxane-based regimens. We developed a standardized chemotherapy education presentation and provided patients with a tool kit that consisted of chemotherapy drug education, a guide to managing side effects, advance directives, and center contact information. Results From May 9, 2014 to June 26, 2015, 144 patients participated in 51 SMART visits. The majority of patients had ovarian cancer and were treated with carboplatin/paclitaxel. Surveyed patients reported being highly satisfied with the group visit and would recommend shared medical appointments to other patients. Conclusions This model of care provides patient education within a framework of social support that empowers patients. Shared medical appointments for oncology patients initiating chemotherapy are both feasible and well accepted.

6059 Background: The epidermal growth factor receptor (EGFR) is expressed in many types of cancer. Fifty to 70% of epithelial ovarian can overexpress EGFR, and its expression has been correlated with poor prognosis features in many cases. While these tumors are chemosensitive to platinum-based therapy, chemoresistance often develops. We conducted a phase I/II trial to examine the efficacy, safety, and toxicity of gefitinib, a tyrosine kinase inhibitor, combined with topotecan in women with recurrent ovarian cancer with EGFR receptor positivity (1+ or greater). Methods: Patients with measurable, recurrent or persistent cancer after treatment with a platinum and paclitaxel-containing regimen were eligible for this study (n = 19). We first used “run-in” dose escalation, in which a conventional 3+3 algorithm was used. Initial treatment was gefitinib 250 mg oral dose daily and topotecan at a dose of 2.0 mg/m2 on days 1, 8, and 15, with cycles repeated every 28 days. Dose escalations were planned for topotecan (Dose Levels 1–3: 2, 3, 4 mg/m2) until the MTD was reached. Next, an additional 10 patients with refractory or progressive ovarian cancer were enrolled in the phase II study. Results: 19 patients received a total of 61 cycles. Median age was 60 years. Histological types of treated patients included 73% serous (n = 14), 12.5% mixed (n = 2), 12.5% transitional (n = 2) and 6.3% clear cell (n = 1). There were 3 patients treated at dose level 1, 3 patients at dose level 2, and 3 patients treated at dose level 3. The maximum tolerated dose was topotecan 4.0mg/m2 IV days 1, 8 and 15, and gefitinib 250mg p.o. QD x28 days. Therefore, dose level 3 was used for the Phase II portion of the trial. Of the 19 patients included in the phase I/II, 3 patients were inevaluable for response to therapy due to toxicity, missed therapy or decline in performance status. Of the 16 patients, 81% patients (n = 13) had progressive disease, 12.5% stable disease (n = 2), and 6% partial response (n = 1). We assessed all 19 patients for adverse events; 60% had treatment-related grade 3 events, primarily blood disorders such as anemia (n = 3, 16%), neutrophil count decrease (n = 4, 21%). Conclusions: This prospective phase I/II clinical trial failed to show sufficient clinical activity of topotecan in combination with gefitinib in patients with EGFR-positive recurrent ovarian, fallopian tube, or peritoneal cancers. The drug combination was relatively well-tolerated in this cohort. As such, the study did not proceed to the next accrual goal secondary to the lack of response. Clinical trial information: NCT00317772.

Two prospective, multicenter clinical trials have demonstrated the feasibility and reproducibility of sentinel lymph node (SLN) biopsy as part of the standard management of early-stage vulvar carcinoma. On the basis of the results of these trials, many gynecologic oncologists have incorporated SLN biopsy for vulvar cancer into their practice. Studies have further shown that SLN biopsy is associated with better quality of life than full lymphadenectomy, is more cost-effective than full lymphadenectomy, and improved pathologic evaluation. A large observational study is currently evaluating the outcomes of patients with early-stage vulvar cancer according to the results of their SLN biopsy and the approach to their care; this study may confirm that full inguinofemoral lymphadenectomy is no longer necessary in most patients with this disease. Here, we review the published data supporting SLN biopsy as part of the standard of care for women with early-stage vulvar cancer and discuss future considerations for the management of this disease. (C) 2015 Elsevier Inc. All rights reserved.

ObjectiveNational guidelines recommend prophylactic anticoagulation for all hospitalized patients with cancer to prevent hospital-acquired venous thromboembolism (VTE). However, adherence to these evidence-based recommended practice patterns remains low. We performed a quality improvement (QI) project to increase VTE pharmacologic prophylaxis rates among patients with gynecologic malignancies hospitalized for nonsurgical indications and evaluated the resulting effect on rates of development of VTE.Materials and MethodsIn June 2011, departmental VTE practice guidelines were implemented for patients with gynecologic malignancies who were hospitalized for nonsurgical indications. A standardized VTE prophylaxis module was added to the admission electronic order sets. Outcome measures included number of admissions receiving VTE pharmacologic prophylaxis within 24 hours of admission; and number of potentially preventable hospital-acquired VTEs diagnosed within 30 and 90 days of discharge. Outcomes were compared between a preguideline implementation cohort (n = 99), a postguideline implementation cohort (n = 127), and a sustainability cohort assessed 2 years after implementation (n = 109). Patients were excluded if upon admission they had a VTE, were considered low risk for VTE, or had a documented contraindication to pharmacologic prophylaxis.ResultsAdministration of pharmacologic prophylaxis within 24 hours of admission increased from 20.8% to 88.2% immediately following the implementation of guidelines, but declined to 71.8% in our sustainability cohort (P < 0.001). There was no difference in VTE incidence among the 3 cohorts [n = 2 (4.2%) vs n = 3 (3.9%) vs n = 3 (4.2%), respectively; P = 1.00].ConclusionsOur QI project improved pharmacologic VTE prophylaxis rates. A small decrease in prophylaxis during the subsequent 2 years suggests a need for continued surveillance to optimize QI initiatives. Despite increased adherence to guidelines, VTE rates did not decline in this high-risk population.

// Sarina A. Piha-Paul 1 , Jennifer J. Wheler 1 , Siqing Fu 1 , Charles Levenback 2 , Karen Lu 2 , Gerald S. Falchook 1 , Aung Naing 1 , David S. Hong 1 , Apostolia M. Tsimberidou 1 , Razelle Kurzrock 3 1 Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), University of Texas MD Anderson Cancer Center, Houston, TX 2 Department of Gynecologic Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 3 Moores Cancer Center, The University of California San Diego, La Jolla, CA, U.S.A Correspondence: Sarina A. Piha-Paul, email: // Keywords : Gynecologic Malignancy, Bevacizumab, Temsirolimus Received : January 31, 2014 Accepted : March 19, 2014 Published : March 20, 2014 Abstract Background: Bevacizumab and temsirolimus are active agents in gynecologic tumors. Temsirolimus attenuates upregulation of HIF-1α levels, a resistance mechanism for antiangiogenics, and targets the PI3-kinase/AKT/mTOR axis, commonly aberrant in these tumors Patients and Methods: We analyzed safety and responses in 41 patients with gynecologic cancers treated as part of a Phase I study of bevacizumab and temsirolimus. Results: Median age of the 41 women was 60 years (range, 33-80 years); median number of prior systemic therapies was 4 (1-11). Grade 3 or 4 treatment-related toxicities included: thrombocytopenia (10%), mucositis (2%), hypertension (2%), hypercholesterolemia (2%), fatigue (7%), elevated aspartate aminotransferase (2%), and neutropenia (2%). Twenty-nine patients (71%) experienced no treatment-related toxicity greater than grade 2. Full FDA-approved doses of both drugs (bevacizumab 15mg/kg IV Q3weeks and temsirolimus 25mg IV weekly) were administered without dose-limiting toxicity. Eight patients (20%) achieved stable disease (SD) ≥ 6 months and 7 patients (17%), a partial response (PR) [total = 15/41 patients (37%)]. Eight of 13 patients (62%) with high-grade serous histology (ovarian or primary peritoneal) achieved SD ≥ 6 months/PR. Conclusion: Bevacizumab and temsirolimus was well tolerated. Thirty-seven percent of heavily-pretreated patients achieved SD ≥ 6 months/PR, suggesting that this combination warrants further study.

256 Background: The mortality index (MI) is a quality metric that measures the ratio of actual mortality to expected mortality among inpatients. Expected mortality is a probability calculation based on patient risks and comorbidities. A MI of < 1.0 represents that fewer patients die while admitted to the hospital than expected. Methods: We formed a multidisciplinary team that included Gynecologic Oncology (GO), Health Information Management, Clinical Informatics, Revenue Operations, Coding and Institutional Compliance experts. Our aim was to decrease the GO MI by 10% within a year. Quality Improvement Assessment Board approval was obtained. GO clinical providers were educated on proper documentation of patient comorbidities and severity of illness. Audits of the documentation were performed by the multidisciplinary team. GO patients perceived at high-risk of inpatient mortality were identified for additional review. All GO inpatient deaths were reviewed at the monthly GO Morbidity and Mortality conference and opportunities for avoidance of inpatient death were discussed. Plan-Do-Study-Act (PDSA) cycles were repeated with adjustments made to the review and education processes. Baseline (BL) 8/2017-7/2018 and interim post-intervention (PI) 11/2018-2/2019 outcomes were compared using the Mann Whitney U test. Results: The BL median number of inpatient deaths per month was 2 (range 0-7), with a median expected mortality of 2.96 (range 1.46-5.11), and a median MI of 0.84 (range 0-1.37). The PI median number of inpatient deaths per month was 2.5 (range 2-5), with a median expected mortality of 4.24 (range 3.77-5.06), and a median MI of 0.56 (range 0.53-1.27). The number of inpatient deaths per month was similar between groups (2 vs 2.5; p = 0.49) but the expected mortality increased from to 2.96 to 4.24 (p = 0.03). MI decreased by 33% between BL and PI (0.84 vs 0.56). Conclusions: Inpatient mortality is an important quality metric. Accurate measurement of expected mortality is critical and requires proper documentation. This can be improved through education, review and frequent assessment by PDSA cycles. Our preliminary results show improvement in accurate documentation and measurement of expected mortality resulting in a decrease in MI.

5570 Background: To determine the correlation between surgeon radiology assessment and laparoscopic scoring in patients with newly diagnosed advanced stage ovarian cancer. Methods: Following IRB approval, 14 gynecologic oncologists from a single institution performed a blinded review of radiology imaging from 20 patients with advanced stage ovarian cancer. All patients previously underwent laparoscopic scoring assessment to determine primary resectability at tumor reductive surgery (TRS) using a validated scoring method from April 2013 to December 2017. The patients with predictive index value (PIV) scores < 8 were offered primary surgery and those with a score ≥8 received neoadjuvant chemotherapy (NACT). Surgeons viewed contrasted CT imaging reports and images from all patients in a blinded fashion and recorded PIV scores using the same validated scoring method. Linear mixed models were conducted to calculate the correlation between radiology and laparoscopic score for each surgeon and as a group. Once the model was fit, the inter-class correlation (ICC) and 95% confidence interval was calculated. Results: Radiology review was performed on 20 patients with advanced stage ovarian cancer who underwent laparoscopic scoring assessment. Most patients had stage IIIC disease (85%) and median laparoscopic score was 9 (range 0-14). Surgeon faculty rank included Assistant Professor (n = 5), Associate Professor (n = 4), and Professor (n = 5). Median surgeon experience during the study period with laparoscopic assessment was 13 cases (range 1-28) and TRS was 22.5 cases (range 2-48). The kappa inter-rater agreement was -0.017 (95% CI 0.023 to -0.005) indicating low inter-rater agreement between radiology review and actual laparoscopic score. The ICC in this model was 0.06 (0.02-0.21) indicating that surgeons do not score the same across all the images. When using a clinical cutoff of PIV of 8, the probability of agreement between radiology and actual laparoscopic score was 0.56 (95% CI: 0.49-0.73). Number of laparoscopic cases, TRS cases, or faculty rank was not significantly associated with agreement. Conclusions: Surgeon radiology review did not correlate highly with actual laparoscopic scoring assessment findings in patients with advanced stage ovarian cancer. 44% of patients in our study may have been inadequately triaged by radiology review alone, which may have led to suboptimal TRS. Our study highlights the utility of laparoscopic scoring assessment to determine resectability over radiology assessment alone in ovarian cancer.

Purpose Current information about the anatomic distribution of lymph node (LN) metastases from cervical cancer is not precise enough for optimal treatment planning for highly conformal radiation therapy. To accurately define the anatomic distribution of these LN metastases, we mapped [ 18 F] fluorodeoxyglucose positron emission tomography (FDG PET)-positive LNs from 50 women with cervical cancer. Methods and Materials Records of patients with cervical cancer treated from 2006 to 2010 who had pretreatment PET/computed tomography (CT) scans available were retrospectively reviewed. Forty-one consecutive patients (group 1) with FDG-avid LNs were identified; because there were few positive paraortic LNs in group 1, 9 additional patients (group 2) with positive paraortic LNs were added. Involved LNs were contoured on individual PET/CT images, mapped to a template CT scan by deformable image registration, and edited as necessary by a diagnostic radiologist and radiation oncologists to most accurately represent the location on the original PET/CT scan. Results We identified 190 FDG-avid LNs, 122 in group 1 and 68 in group 2. The highest concentrations of FDG-avid nodes were in the external iliac, common iliac, and paraortic regions. The anatomic distribution of the 122 positive LNs in group 1 was as follows: external iliac, 78 (63.9%); common iliac, 21 (17.2%); paraortic, 9 (7.4%); internal iliac, 8 (6.6%); presacral, 2 (1.6%); perirectal, 2 (1.6%); and medial inguinal, 2 (1.6%). Twelve pelvic LNs were not fully covered when the clinical target volume was defined according to Radiation Therapy Oncology Group guidelines for intensity modulated radiation therapy for cervical cancer. Conclusions Our findings clarify nodal volumes at risk and can be used to improve target definition in conformal radiation therapy for cervical cancer. Our findings suggest several areas that may not be adequately covered by contours described in available atlases.

Lymphatic mapping studies in women with cervical cancer typically identify sentinel nodes (SLNs) in the pelvis and not the parametrium. We added India ink as a mapping agent to determine whether this would allow us to pathologically identify sentinel parametrial nodes and to test our hypothesis that the parametrial nodes are the true SLNs in women with cervical cancer.We performed lymphatic mapping and SLN biopsy in 20 women with early-stage cervical cancer undergoing radical hysterectomy or trachelectomy using a "triple injection" technique with blue dye, radiocolloid, and India ink. Pathologic processing of parametrium and nodal tissue was then performed to identify India ink in specimens.On pathology review, 15 (75%) patients had a parametrial node identified, and 9 patients (45%) had bilateral parametrial nodes identified; the median number of parametrial nodes identified was 2 (range, 0-7). India ink was seen in at least 1 parametrial node in 13 (87%) of the 15 patients with a parametrial node identified pathologically. Of the 9 patients with bilateral parametrial nodes identified pathologically, only 5 (54%) had bilateral parametrial nodes containing India ink. India ink was found in 26 (44%) of 59 SLNs and only 1 (0.3%) of 289 non-SLNs. In 5 patients, India ink was seen in a SLN on the same side of the pelvis where a parametrial node was identified but not microscopically black.There appears to be direct drainage of cervical lesions to pelvic nodal basins bypassing small parametrial nodes. Parametrial nodes, therefore, may not always be the SLNs in women with cervical cancer.

Advanced stage leiomyosarcoma (LMS) is incurable with current systemic antitumor therapies. Therefore, there is clinical interest in exploring novel therapeutic regimens to treat LMS. We reviewed the medical records of 75 consecutive patients with histologically confirmed metastatic LMS, who had been referred to the Clinical Center for Targeted Therapy at MD Anderson Cancer Center. To lay the foundation for potential phase I trials for the treatment of advanced LMS, we analyzed tumor response and survival outcome data. The frequent hotspot gene aberrations that we observed were the TP53 mutation (65%) and RB1 loss/mutation (45%) detected by Sequenom or next‐generation sequencing. Among patients treated with gene aberration‐related phase I trial therapy, the median progression‐free survival was 5.8 months and the median overall survival was 15.9 months, significantly better than in patients without therapy (1.9 months, P = 0.001; and 8.7 months, P = 0.013, respectively). Independent risk factors that predicted shorter overall survival included hemoglobin

Importance A 2009 randomized clinical trial demonstrated that using cancer antigen 125 (CA-125) tests for routine surveillance in ovarian cancer increases the use of chemotherapy and decreases patients’ quality of life without improving survival, compared with clinical observation. The Society of Gynecologic Oncology guidelines categorize CA-125 testing as optional and discourage the use of radiographic imaging for routine surveillance. To date, few studies have examined the use of CA-125 tests in clinical practice. Objectives To examine the use of CA-125 tests and computed tomographic (CT) scans in clinical practice before and after the 2009 randomized clinical trial and to estimate the economic effect of surveillance testing. Design, Setting, and Participants A prospective cohort of 1241 women with ovarian cancer in clinical remission after completion of primary cytoreductive surgery and chemotherapy at 6 National Cancer Institute–designated cancer centers between January 1, 2004, and December 31, 2011, was followed up through December 31, 2012, to study the use of CA-125 tests and CT scans before and after 2009. Data analysis was conducted from April 9, 2014, to March 28, 2016. Main Outcomes and Measures The use of CA-125 tests and CT scans before and after 2009. Secondary outcomes included the time from CA-125 markers doubling to retreatment among women who experienced a rise in CA-125 markers before and after 2009, and the costs associated with surveillance testing using 2015 Medicare reimbursement rates. Results Among 1241 women (mean [SD] age 59 [12] years; 1112 white [89.6%]), the use of CA-125 testing and CT scans was similar during the study period. During 12 months of surveillance, the cumulative incidence of patients undergoing 3 or more CA-125 tests was 86% in 2004-2009 vs 91% in 2010-2012 ( P = .95), and the cumulative incidence of patients undergoing more than 1 CT scan was 81% in 2004-2009 vs 78% in 2010-2012 ( P = .50). Among women whose CA-125 markers doubled (n = 511), there was no significant difference in the time to retreatment with chemotherapy before and after 2009 (median, 2.8 vs 3.5 months; P = .40). During a 12-month period, there was a mean of 4.6 CA-125 tests and 1.7 CT scans performed per patient, resulting in a US population surveillance cost estimate of $1 999 029 per year for CA-125 tests alone and $16 194 647 per year with CT scans added. Conclusions and Relevance CA-125 tests and CT scans are still routinely used for surveillance testing in patients with ovarian cancer, although their benefit has not been proven and their use may have significant implications for patients’ quality of life as well as costs.

Surgical site infections (SSIs) lead to increased patient morbidity and healthcare costs. Our objective was to decrease the SSI rate following gynecologic surgery. Adult patients undergoing abdominal surgery for gynecologic malignancy or benign disease received the following: patient education; preoperative antibacterial soap; appropriate antibiotic prophylaxis; change of gloves and use of clean instruments at surgical closure; surgical dressing for 48 h; and a post-discharge phone call. The baseline SSI rate was determined retrospectively (1 April 2014–30 June 2014), while the post-intervention SSI rate was determined prospectively (16 February 2015–15 October 2015). The main outcome was the overall SSI rate with secondary outcomes, including the rate of superficial, deep, incisional and organ space infection, as well as the cost effectiveness of the bundle. A total of 232 baseline and 555 post-intervention patients were included in the study. No differences were observed between the baseline and post-intervention groups with regard to median body mass index (BMI), surgical approach, receipt of preoperative chemotherapy and/or radiation therapy, and cases including bowel surgery. Overall, the SSI rate decreased significantly from baseline [12.5 %] to post-intervention [7.4 %] (odds ratio [OR] 0.56, 90 % confidence interval [CI] 0.37–0.85; p = 0.01). A 40 % decrease was noted in the rate of superficial and deep infections (9.5 vs. 5.9 %; OR 0.60, 90 % CI 0.38–0.97; p = 0.04) and SSIs after open surgery (21.4 vs. 13.2 %; OR 0.56, 90 % CI 0.34–0.92; p = 0.03). The estimated cost of the intervention was $19.26/case and the net total amount saved during the post-intervention period was $65,625 month. This bundled intervention led to a significant decrease in the overall SSI rate and was cost effective. The largest decreases in SSIs were in incisional infections and following open surgery.

Objective The primary purpose of this study was to determine the average patient cost for filling a prescription for extended-duration enoxaparin prophylaxis. Methods Women who underwent major abdominal/pelvic surgery for histologically confirmed gynecologic malignancy were included. Patients who underwent minimally invasive surgery, had benign disease or were on treatment for existing VTE were excluded. Pharmacy resource specialists electronically submitted test prescriptions to verify enoxaparin coverage in the outpatient setting prior to hospital discharge. Patient co-pay information collected included: the number of patients requiring prescription insurance prior authorization, those qualifying for the Lovenox Patient Assistance Program® (PAP) and insurance status. Results Three hundred and sixty-four patients were discharged with extended-duration enoxaparin prophylaxis for 28days between October 2009 and May 2011. The average patient cost to complete 28days of enoxaparin prophylaxis was $62 (median $21, range $0–1210). Prior authorization was required for 32 patients (10%). Two patients (0.6%) qualified for the Lovenox Patient Assistance Program®. A decrease in the average patient cost from $71 to $52 (median $30 to $10) was observed after generic enoxaparin approval in July 2011. Conclusion Our results show that at least 90% of patients filled their prescription of extended-duration enoxaparin prophylaxis after major abdominal surgery for cancer regardless of cost.

Objective To evaluate the efficacy and tolerability of imatinib mesylate in patients with recurrent low-grade serous carcinoma (LGSC) of the ovary, peritoneum, or fallopian tube. Methods This open-label, single-institution phase II trial enrolled patients with platinum-resistant LGSC who had measurable disease, had received up to 4 platinum- and/or taxane-containing chemotherapy regimens, and had been previously screened for at least one imatinib targeted biomarker (c-kit, platelet-derived growth factor receptor [PDGFR]-β, or bcr–abl). Imatinib (600mg) was administered daily for one 6-week course and continued in the absence of toxicity and disease progression. Results Thirteen patients were enrolled; 12 were evaluable for toxicity, and 11 were evaluable for response. A total of 17 courses were administered (median, 1 course; range, 1–5 courses). Complete or partial responses were not observed. One patient had stable disease for 7.3months. c-Kit, bcr–abl, or PDGFR-β were present in 48%, 77%, and 100% of patients, respectively. No correlation between best response (stable disease) and the presence of imatinib-targeted biomarkers was observed. Adverse events included grade 3 skin rash in one patient leading to discontinuation of the drug, and grade 3 febrile neutropenia and grade 2 weight gain in two patients leading to dose reductions. The most common grade 1 or 2 toxicities were fatigue (66%), nausea/vomiting (66%), and diarrhea (41%); grade 3 toxicities included skin rash and granulocytopenia events. No grade 4 or 5 toxicities were observed. The median progression-free survival time was 1.3months (95% CI, 1.27, 1.40months), and the median overall survival time was 14.9months (95% CI, 11.0, 18.9months). Conclusion Imatinib is well-tolerated but has no activity in patients with platinum- and taxane-resistant LGSC or the ovary, peritoneum, or fallopian tube.

PurposeThe objective of the study was to determine the impact of brachytherapy implant quality on outcome among cervical cancer patients treated on Radiation Therapy Oncology Group prospective trials 0116 and 0128.MethodsAll enrolled patients received concurrent chemoradiation followed by brachytherapy. Individual brachytherapy parameters, including the symmetry of ovoids in relation to the tandem, displacement of ovoids in relation to the cervical os, tandem bisecting the ovoids, tandem in the midpelvis, and appropriateness of packing, were scored for each implant. Multivariate Cox proportional hazards models were constructed for each parameter for local recurrence (LR), regional recurrence, distant recurrence, disease-free survival (DFS), and overall survival.ResultsRecords for 103 patients were analyzed. The median follow-up time was 24.5 months. Patients with unacceptable symmetry of ovoids to the tandem had a significantly higher risk of LR than patients in the acceptable group (hazard ratio [HR], 2.67; 95% confidence interval [CI], 1.11–6.45;P= 0.03). Patients with displacement of ovoids in relation to the cervical os had a significantly increased risk of LR (HR, 2.50; 95% CI, 1.05–5.93;P= 0.04) and a lower DFS rate (HR, 2.28; 95% CI, 1.18–4.41;P= 0.01). Inappropriate placement of packing resulted in a lower DFS rate (HR, 2.06; 95% CI, 1.08–3.92;P= 0.03).ConclusionsAssessment of the quality of a brachytherapy implant is imperative, as proper placement has an impact on patient DFS. If feasible, inappropriate placements should be corrected before treatment initiation. Brachytherapy applicators for cervical cancer should preferably be placed and assessed by experienced practitioners.

BACKGROUND: Up to one third of oncologists experience burnout. The objective was to determine correlates of work related stress in gynecologic oncologists (GOs) METHODS: Using an online tool, we surveyed 273 members of the International Gynecologic Cancer (IGCS) Society (60% from North America) to examine demographic, psychological and spiritual correlates of work related stress (WRS) and burnout. Measures of death anxiety (DA) and locus of control (LOC) were also administered. RESULTS: WRS did not correlate with religion, religiosity, race, or gender, but did correlate with DA (r = 0.23, p = 0.0006). WRS also was also associated younger age (p = 0.01) and fewer years out of training (p= 0.0286), higher scores on LOC Chance (r = 0.18, p = 0.007), higher scores on Powerful Other (r = 0.30, p < 0.0001), and lower scores on LOC Internality (r = −0.30, p < 0.0001). CONCLUSION: Responses from younger and less experienced GOs, correlate with higher WRS scores especially if their LOC is weighted toward chance and powerful others. Responses of GO’s with these two characteristics also correlate with higher DA scores and reports of difficulty talking about death.

To compare intra-operative, postoperative and pathologic outcomes of three surgical approaches to radical hysterectomy and bilateral pelvic lymph node dissection over a three year time period during which all three approaches were used.We reviewed all patients who underwent radical hysterectomy with pelvic lymph node dissection between 1/2007 and 11/2010. Comparison was made between robotic, laparoscopic and open procedures in regard to surgical times, complication rates, and pathologic findings.A total of 95 radical hysterectomy procedures were performed during the study period: 30 open (RAH), 31 laparoscopic (LRH) and 34 robotic (RRH). There were no differences in age, body mass index or other demographic factors between the groups. Operative time was significantly shorter in the RAH compared to LRH and RRH (265 vs 338 vs 328min, p=0.002). Estimated blood loss was significantly lower in LRH and RRH compared with RAH (100 vs 100 vs 350mL, p0.001). Thirteen (24%) of RAH required blood transfusion. Conversion rates were higher in the LRH (16%) compared to RRH (3%) although not significant (p=0.10). Median length of stay was significantly shorter in RRH (1day) vs LRH or RAH (2 vs 4days, p0.01). Pathologic findings were similar among all groups.Minimally invasive surgery has made a significant impact on patients undergoing radical hysterectomy including decrease in blood loss and transfusion rates however; operative times were significantly longer compared to open radical hysterectomy. Our findings suggest that the robotic approach may have the added benefit of even shorter length of stay compared to traditional laparoscopy.

The validation of sentinel lymph node (SLN) concept in melanoma and breast cancer has established a new paradigm in cancer metastasis that, in general, cancer cells spread in a orderly fashion from the primary site to the SLNs in the regional nodal basin and then to the distant sites. In this review article, we examine the development of SLN concept in penile carcinoma, melanoma and breast carcinoma and its application to other solid cancers with emphasis of the relationship between micrometastasis in SLNs and clinical outcomes.

Several controversies surround lymphadenectomy for endometrial cancer; surgical approach, who to stage, and the anatomic borders of the lymphadenectomy. The purpose of this study was to identify practice patterns among gynecologic oncologists when performing a lymph node evaluation during staging for endometrial cancer.A self-administered survey was sent via email to all SGO members on 3 occasions between 2/09 and 4/09. The survey addressed surgical approach, algorithms used to determine staging, and anatomic landmarks defining lymphadenectomy.Four hundred and six members (40%) responded. Eighty-two percent completed fellowship and 14% were fellows. Thirty-four percent finished fellowship in 2000 or later. Eighty-five percent educate fellows/residents in either academic (65%) or private practice settings (20%). For a majority of cases 40% prefer laparotomy, 31% perform robotic surgery, and 29% use laparoscopy. Minimally invasive surgery was associated with university-based practice (p=0.048). Most (53%) never/rarely use frozen section to determine whether or not to perform lymphadenectomy. A majority perform staging on all grade 2 and grade 3 cancers (66% and 90%, respectively). When performing paraaortic lymphadenectomy, 50% of respondents use the IMA as the upper border and 11% take the dissection to the renal vessels. Participants who completed fellowship in 2000 or later were less likely to go to the renal vessels (p=0.002).Current controversies in surgical staging for endometrial cancer are reflected in the practice patterns among gynecologic oncologists. At this point it is unclear if standardizing surgical practice patterns will improve outcomes for patients with endometrial cancer.

5504Background: We sought to determine the recommended phase II dose (RP2D) of olaparib (O) and vistusertib (V) and evaluate molecular markers of response. Methods:Two oral schedules for V were exp...

An expert panel was formed for the 6th biennial International Sentinel Node Society to review the status of sentinel lymph node biopsy (SLNB) in gynecologic oncology. This paper presents the opinion of the experts who participated regarding indications for SLNB, technical considerations, and directions for future investigation.

To estimate the incidence of parametrial involvement and to evaluate factors associated with parametrial spread in women with early-stage cervical cancer and to identify a cohort of patients at low risk for parametrial spread who may benefit from less radical surgery.We reviewed all patients who underwent radical hysterectomy and pelvic lymphadenectomy for invasive cervical cancer between 1990 and 2006. All women with squamous, adenocarcinoma, or adenosquamous disease, stage IA2-IB1, who underwent completed radical hysterectomy were included in the analysis. Normally distributed continuous variables were compared using Student's t-test for independent samples to analyze the outcome of positive or negative parametrial involvement.Three hundred fifty patients met the inclusion criteria. Overall, 27 women (7.7%) had parametrial involvement. The majority of specimens with parametrial involvement (52%) had tumor spread through direct microscopic extension. Patients with parametrial involvement were more likely to have a primary tumor size larger than 2 cm (larger than 2 cm: 14%, smaller than 2 cm: 4%, P=.001), higher histologic grade (grade 3: 12%, grades 1 and 2: 3%, P=.01), lymphovascular space invasion (positive: 12%, negative: 3%, P=.002), and metastasis to the pelvic lymph nodes (positive: 31%, negative: 4%, P.001). One hundred twenty-five women (36%) had squamous, adenocarcinoma, or adenosquamous lesions, all grades, with primary tumor size 2 cm or smaller and no lymphovascular space invasion. In this group of patients, there was no pathologic evidence of parametrial involvement.We were able to retrospectively identify a cohort of women with early-stage cervical cancer who were at very low risk for parametrial involvement. If prospective application of these findings confirms our results, less radical surgery-such as simple hysterectomy, simple trachelectomy, or conization-with pelvic lymphadenectomy may be a reasonable therapeutic option for women with primary tumors 2 cm or smaller and no lymphovascular space invasion.III.

The purpose of this study was to evaluate the impact of increasing the magnesium (Mg(2+)) supplementation in the pre- and posthydration of patients receiving cisplatin plus radiation (CisXRT) to prevent chemotherapy-induced hypomagnesemia (CIH) events.The study was conducted on newly diagnosed cervical cancer patients receiving CisXRT. The first prospective intervention to prevent CIH was to increase the pre- and posthydration Mg(2+) from 1 to 2 g. After completion of the first intervention, the analysis demonstrated the persistent occurrence of CIH on cycle 3, and later, a second intervention was implemented to increase Mg(2+) to 3 g in the pre- and posthydration. Patients that failed to complete at least five cycles or received cisplatin in combination with another chemotherapy regimen were excluded from the study. Baseline group included 70 patients that had received CisXRT prior to any changes in magnesium supplementation.There were 62.8% (44/70) and 32.6% (22/70) of patients with episodes of CIH in the baseline and first intervention groups, respectively (P = 0.007). In the second intervention group, a 49.6% decrease in the total number of episodes compared to control group was observed. Patients in the second intervention group showed a 100% improvement incidence of persistent CIH over the two other cohorts (P = 0.001).The increase of Mg(2+) to 2 g for the initial two cycles and then to 3 g with the third cycle of CisXRT therapy prevented episodes of CIH and decreased associated treatment delays.

Hospital records of 4490 patients treated for International Federation of Gynecology and Obstetrics (FIGO) stage IB, IIA, or IIB carcinoma of the cervix between 1960 and 2001 at 1 institution were reviewed. Outcomes were estimated using the Kaplan-Meier method and compared using the log-rank method. A proportional hazards regression model was used to evaluate the relative importance of predictive factors. The rates of disease-specific survival and pelvic disease control were strongly correlated with tumor diameter, FIGO stage, histological subtype, and clinical node status. Regression analysis demonstrated that a diameter of greater than 4 cm, a diameter of greater than 6 cm, FIGO stage II (vs IB), the presence and level of lymph node involvement, and histological subtype were all highly significant independent predictors of poor disease-specific survival. Intermediate tumor-diameter categories (>5 cm or >7 cm) and FIGO stage IIB (vs IB or IIA) did not contribute significant additional information to the model. Only a tumor diameter of greater than 4 cm, a diameter of greater than 6 cm, the presence of lymph node involvement, and histological subtype were independent predictors of pelvic disease control. On the basis of these results, we propose dividing each of the FIGO categories IB, IIA, and IIB into 3 groups according to clinical tumor diameter: (1) less than or equal to 4 cm, (2) 4.1 to 6 cm, and (3) greater than 6 cm. The proposed modified system would provide more accurate prognostic information, facilitate comparisons, and maintain continuity with the current staging system.

Study Objective The purpose of our study was to report on our case series of 7 patients with gynecologic cancer who underwent laparoscopic colostomy for elective fecal diversion. Our aim was to retrospectively estimate feasibility, safety, and efficacy of the laparoscopic approach in the setting of gynecologic malignancy, given the high incidence of earlier abdominal surgery and pelvic radiation treatment in this select population. Design Retrospective chart review (Canadian Task Force classification I). Setting University of Texas, M.D. Anderson Cancer Center. Patients All patients with a history of gynecologic cancers who underwent laparoscopic colostomy during the study period. Interventions We retrospectively reviewed all patients who underwent elective laparoscopic diverting colostomy in our department of gynecologic oncology. Surgical indications, medical history, operative and stomal complications, estimated blood loss, return of bowel function, and length of hospital stay were collected. Measurements and Main Results Seven patients underwent laparoscopic colostomy during the study period. Six of these patients underwent an end descending colostomy, and 1 patient underwent a loop colostomy. Indications included rectovaginal fistula (n = 5), colonic/pelvic fistula (n = 1), or large bowel obstruction (n = 1). No intraoperative or postoperative complications occurred, nor did any conversions to laparotomy. The median blood loss was 50 mL (range 10–75). Median operative time was 102 minutes (range 69–159). Six (86%) patients had a history of pelvic radiation. In addition, 3 (43%) patients had a history of laparotomy. The median patient weight was 59.8 kg (range 47.1–82.2). The median time to tolerance of a regular diet was 2 days (range 1–3) and the median length of hospital stay was 3 days (range 2–4). No immediate or delayed stomal complications were noted with a median follow-up of 6 months (range 1–15). Conclusion Laparoscopic colostomy in advanced gynecologic cancer may be a safe and feasible technique with minimal morbidity, rapid return of bowel function, and short hospital stay.

The technique of sentinel lymph node (SLN) detection is increasingly being applied in patients with uterine cervix carcinoma. This study presents the pathologic findings of SLNs in 48 such patients. The institutional pathology files were searched for all patients with a diagnosis of cervical squamous cell carcinoma who had SLNs reported. Patient age, follow-up, tumor size, presence/absence of lymphatic invasion, number and status of SLNs and non-SLNs, location of SLNs, and size of metastases in SLNs were recorded. All SLNs were sectioned in 2-mm slices perpendicular to the long axis and submitted entirely for microscopic examination. For all SLNs negative on the initial hematoxylin and eosin (HE) stained slides, an ultrastaging protocol was performed consisting of 5 sets of slides at 40-mum intervals (1 HE slide+2 unstained slides), representing an additional 5 intervals. Lymph nodes negative by the additional HE intervals had immunohistochemistry for cytokeratin performed on 1 unstained slide. Forty-eight patients ranging from 25 to 62 years of age had a total of 208 SLNs removed. Fifteen (31%) patients had positive SLNs with 1 to 5 positive SLNs per case. The metastasis size ranged from a single cell to 27 mm. Twelve patients had metastasis detected by routine processing in 23 SLNs, whereas ultrastaging detected metastases in 3 SLNs of 3 additional patients. In 2 patients with metastasis detected by ultrastaging, the metastasis was detected by wide HE intervals (level 2 for 1 patient; level 3 for 1 patient); in 1 patient, the metastasis was detected only by immunohistochemistry and consisted of a single cell. Of the 15 patients with positive SLNs, 3 patients had a total of 6 positive non-SLNs. All of the patients with a positive SLN are currently living. Thirty-three (69%) patients had negative SLNs. Of these, 1 patient had a single positive non-SLN for a false negative rate of 6.25%. Negative SLN predicts negative non-SLN. For most patients with a positive SLN, the SLN will be the only metastasis detected; a minority of patients with a positive SLN may have a positive non-SLN.