Robotic versus vaginal radical trachelectomy for reproductive-aged patients with early-stage cervical carcinoma: A multi-center cohort study.

BACKGROUND: A randomized non-inferiority trial showed worse survival in women with early-stage cervical cancer treated with radical hysterectomy by minimally invasive approach compared to laparotomy; the impact of surgical approach on survival following radical trachelectomy is unknown. OBJECTIVE: To examine oncologic outcomes in women with early-stage cervical cancer who underwent robotic or vaginal radical trachelectomy at Canadian cancer centers with the highest volumes of radical trachelectomy procedures. STUDY DESIGN: Retrospective multi-centre cohort analysis which includes patients who had surgery between 2006 and 2019. Women with International FIGO 2009 stage IA-IB cervical cancer who underwent radical trachelectomy and lymph node assessment were grouped by surgical approach (vaginal versus robotic surgery). RESULTS: A total of 197 patients were included from 4 regional referral centres. 56 women underwent robotic radical trachelectomy and 141 underwent vaginal radical trachelectomy. All patients had lymph node assessment by a minimally invasive technique. Median age was 32 years, median tumor size was 12 mm, and median depth of invasion was 5 mm. Recurrence-free survival was 97% in both groups at a median follow-up of 57 months. On multivariable analysis, after adjusting for previously chosen confounders (high risk pathologic criteria, tumor size, and LVSI) there was no statistically significant difference in PFS between the 2 groups (HR 2.1, 95%CI 0.3-7.1, p = 0.5). Tumor size larger than 2 cm (HR 9.4, 95%CI 2.8-26, p = 0.003) was the only variable predictive of recurrence. CONCLUSION: Survival outcomes were excellent in both cohorts of patients undergoing robotic vs. vaginal radical trachelectomy. The surgical approach was not significantly associated with risk of recurrence after adjusting for clinically important confounders.

Role of HPV in the Prediction of Persistence/Recurrence After Treatment for Cervical Precancer.

OBJECTIVES: (1) To determine the role of human papillomavirus (HPV) testing after excisional treatment of cervical precancer. (2) To determine clinical factors associated with persistence of cervical precancer post-treatment. METHODS: A retrospective chart review was conducted including patients who had a loop electrosurgical excision procedure (LEEP) for cervical precancer (cervical intraepithelial neoplasia 3/adenocarcinoma in situ/high-grade squamous intraepithelial lesions [HSIL]). All patients treated between 2016 and 2018 at a tertiary centre colposcopy unit were included. Persistence/recurrence of disease was defined as high-grade cytology or histology identified during the time of follow-up. Univariate and multivariate regression models were performed to identify factors associated with persistence/recurrence and HPV positivity at exit testing. RESULTS: A total of 284 patients were included. The median follow-up time was 19 months. Of the LEEP specimens, 90.8% (n = 258) demonstrated HSIL and 3.9% (n = 11) had adenocarcinoma in situ. 28.5% (n = 81) of the LEEP specimens had positive margins. In follow-up, 72.9% had negative cytology, 17.6% had atypical squamous cells of undetermined significance/low-grade SIL, 1.8% had atypical squamous cells, HSIL cannot be excluded/low-grade SIL-H, and 6.7% had HSIL. At the final follow-up, 27.8% (n = 79) were HPV+. Overall rate of persistence/recurrence was 11.3% (n = 32); median time to persistence/recurrence was 6.5 months. Multivariate regression models demonstrated that follow-up HPV positivity (OR = 22.0) and positive margins (OR = 3.7) were significantly associated with persistence/recurrence. Similarly, in univariate regression models, positive margins were significant (OR = 2.2) for predicting HPV positivity in exit testing. CONCLUSIONS: Persistence/recurrence of precancer can occur due to incomplete treatment of lesions by local excision and by the persistence of HPV infection. Surveillance strategies for women treated for cervical precancer require a risk-based approach and should rely on HPV testing.

Apixaban for extended postoperative thromboprophylaxis in gynecologic oncology patients undergoing laparotomy.

INTRODUCTION: Venous thromboembolic events represent the second most frequent cause of mortality in cancer patients. Recent literature shows that direct oral anticoagulants (DOAC) are at least as effective and safe as low molecular weight heparin for postoperative thromboprophylaxis. However, this practice has not been broadly adopted in gynecologic oncology. The aim of this study was to evaluate clinical effectiveness and safety of apixaban for extended thromboprophylaxis in comparison to enoxaparin after laparotomies for gynecologic oncology patients. METHODS: The Gynecologic Oncology Division at a large tertiary center transitioned from enoxaparin 40 mg daily to apixaban 2.5 mg BID for 28 days after laparotomies for gynecologic malignancies in November 2020. This real-world study compared patients post-transition (November 2020 to July 2021 (n = 112)) to a historical cohort (January to November 2020 (n = 144)), using the institutional National Surgical Quality Improvement Program (NSQIP) database. All Canadian gynecologic oncology centers were surveyed to assess postoperative DOAC utilization. RESULTS: Patient characteristics were similar between groups. No difference was found between total venous thromboembolism rates (4% vs. 3%, p = 0.49). No difference was found in postoperative readmission (5% vs. 6%, p = 0.50). Of the 7 readmissions in the enoxaparin group, one was due to bleeding requiring transfusion; there were no readmissions for bleeding in the apixaban group. No patient required a reoperation for bleeding. Thirteen percent of the 20 Canadian centers have transitioned to extended apixaban thromboprophylaxis. CONCLUSIONS: Apixaban for 28-day postoperative thromboprophylaxis was found to be an effective and safe alternative to enoxaparin after laparotomies in a real-world cohort of gynecologic oncology patients.

Addressing the diagnostic and therapeutic dilemmas of ovarian immature teratoma: Report from a clinicopathologic consensus conference.

Ovarian immature teratoma is a rare subtype of germ cell tumour that can be pure or associated with non-teratomatous germ cell tumour elements and is graded based on extent of the immature neuroectodermal component. Immature teratoma (IT) can also be associated with somatic differentiation in the form of sarcoma, carcinoma, or extensive immature neuroectodermal elements and may produce low levels of serum alpha-fetoprotein. Variable interpretation of these issues underlies diagnostic and management dilemmas, resulting in substantial practice differences between paediatric and adult women with IT. The Malignant Germ Cell International Consortium (MaGIC) convened oncologists, surgeons, and pathologists to address the following crucial clinicopathologic issues related to IT: (1) grading of IT, (2) definition and significance of 'microscopic' yolk sac tumour, (3) transformation to a somatic malignancy, and (4) interpretation of serum tumour biomarkers. This review highlights the discussion, conclusions, and suggested next steps from this clinicopathologic conference.

The accuracy of intraoperative frozen section examination of sentinel lymph nodes in squamous cell cancer of the vulva.

OBJECTIVE: To assess the diagnostic accuracy of intraoperative pathologic examination of sentinel lymph nodes (SLNs) and patient outcomes in vulva cancer. METHODS: This retrospective study included patients with unifocal, <4 cm, invasive vulvar squamous cell carcinoma and clinically negative groin nodes treated with SLN biopsy from January 2008-March 2020. Intraoperative SLN frozen section and final pathology were compared. If the SLN was negative, inguinal femoral lymphadenectomy (IFLD) was omitted. Recurrence location and groin recurrence free survival (RFS) were assessed. RESULTS: The SLN cohort included 173 patients, with 258 groins. On frozen section, there were 36/258 positive and 222 negative groins. On final pathology, there were 39/258 positive: 31 macrometastases, 6 micrometastases, 2 isolated tumor cells (ITCs) and 219 negative groins. The sensitivity, specificity, PPV and NPV for intraoperative detection of metastatic disease, was 89.7% and 99.5%, 97.2% and 98.2%, respectively. There was 1 false positive and 4 false negative frozen section results where final pathology revealed 2 ITCs, 1 micrometastasis and 1 macrometastasis. Based on intraoperative results, thirty patients (17.3%) underwent immediate IFLD. Median follow up was 38.0 (1-137.8) months. The 3-year groin RFS was 91.6% (95% CI 86.2-97.4%) for negative SLNs and 64.6% (95% CI 46.5-89.7%) for positive SLNs on frozen section. Similarly, the 3-year groin RFS was 91.7% (95% CI 86.3-97.4%) for negative, 58.4% (95% CI 38.5-87.7%) for macrometastases and 100% for micrometastases/ITCs on final pathology. CONCLUSIONS: Intraoperative assessment of SLNs is accurate to determine need for IFLD and does not compromise patient outcomes in vulvar cancer.

Radiotherapy Versus Inguinofemoral Lymphadenectomy as Treatment for Vulvar Cancer Patients With Micrometastases in the Sentinel Node: Results of GROINSS-V II.

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.

Trebananib or placebo plus carboplatin and paclitaxel as first-line treatment for advanced ovarian cancer (TRINOVA-3/ENGOT-ov2/GOG-3001): a randomised, double-blind, phase 3 trial.

BACKGROUND: Angiopoietin 1 and 2 regulate angiogenesis and vascular remodelling by interacting with the tyrosine kinase receptor Tie2, and inhibition of angiogenesis has shown promise in the treatment of ovarian cancer. We aimed to assess whether trebananib, a peptibody that inhibits binding of angiopoietin 1 and 2 to Tie2, improved progression-free survival when added to carboplatin and paclitaxel as first-line therapy in advanced epithelial ovarian, primary fallopian tube, or peritoneal cancer in a phase 3 clinical trial. METHODS: TRINOVA-3, a multicentre, multinational, phase 3, double-blind study, was done at 206 investigational sites (hospitals and cancer centres) in 14 countries. Eligible patients were aged 18 years or older with biopsy-confirmed International Federation of Gynecology and Obstetrics (FIGO) stage III to IV epithelial ovarian, primary peritoneal, or fallopian tube cancers, and an ECOG performance status of 0 or 1. Eligible patients were randomly assigned (2:1) using a permuted block method (block size of six patients) to receive six cycles of paclitaxel (175 mg/m2) and carboplatin (area under the serum concentration-time curve 5 or 6) every 3 weeks, plus weekly intravenous trebananib 15 mg/kg or placebo. Maintenance therapy with trebananib or placebo continued for up to 18 additional months. The primary endpoint was progression-free survival, as assessed by the investigators, in the intention-to-treat population. Safety analyses included patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, number NCT01493505, and is complete. FINDINGS: Between Jan 30, 2012, and Feb 25, 2014, 1164 patients were screened and 1015 eligible patients were randomly allocated to treatment (678 to trebananib and 337 to placebo). After a median follow-up of 27·4 months (IQR 17·7-34·2), 626 patients had progression-free survival events (405 [60%] of 678 in the trebananib group and 221 [66%] of 337 in the placebo group). Median progression-free survival did not differ between the trebananib group (15·9 months [15·0-17·6]) and the placebo group (15·0 months [12·6-16·1]) groups (hazard ratio 0·93 [95% CI 0·79-1·09]; p=0·36). 512 (76%) of 675 patients in the trebananib group and 237 (71%) of 336 in the placebo group had grade 3 or worse treatment-emergent adverse events; of which the most common events were neutropenia (trebananib 238 [35%] vs placebo 126 [38%]) anaemia (76 [11%] vs 40 [12%]), and leucopenia (81 [12%] vs 35 [10%]). 269 (40%) patients in the trebananib group and 104 (31%) in the placebo group had serious adverse events. Two fatal adverse events in the trebananib group were considered related to trebananib, paclitaxel, and carboplatin (lung infection and neutropenic colitis); two were considered to be related to paclitaxel and carboplatin (general physical health deterioration and platelet count decreased). No treatment-related fatal adverse events occurred in the placebo group. INTERPRETATION: Trebananib plus carboplatin and paclitaxel did not improve progression-free survival as first-line treatment for advanced ovarian cancer. The combination of trebananib plus carboplatin and paclitaxel did not produce new safety signals. These results show that trebananib in combination with carboplatin and paclitaxel is minimally effective in this patient population. FUNDING: Amgen.

Impact of a preventive bundle to reduce surgical site infections in gynecologic oncology.

OBJECTIVE: To assess the impact of a surgical site infection (SSI) prevention bundle for Gynecologic Oncology patients at a large academic tertiary centre in Toronto, Canada. METHODS: A SSI prevention bundle was implemented in February 2017 including: preoperative chlorhexidine shower, prophylactic antibiotics, glycemic control, normothermia, and separate closing tray. Data were collected prospectively using the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) institutional data, and chart review of surgeries between January 2016 and September 2017 was performed. The primary outcome was rate of SSIs, secondary outcomes were: superficial, deep and organ space SSIs, sepsis, wound disruption, length of stay, 30-day readmission and reoperation. Logistic regression analysis was conducted to identify predictors of SSIs. RESULTS: 339 baseline and 224 post-intervention patients were included. 53 incurred one or more SSIs: 43 superficial, 6 deep, and 14 organ-space. The bundle decreased overall SSIs by 55% (12.1% to 5.4%, p = 0.008) and superficial SSIs by 54% (9.7% to 4.5%, p = 0.023). Improvement was sustained for 6 quarters. No significant difference was found in other secondary outcomes. On multivariable analysis, surgery in the pre-bundle period, BMI ≥30, laparotomies and longer operative duration were independent risk factors for overall SSIs (OR 2.23, 95% CI 1.06-5.06, -OR 3.01, 95% CI 1.57 - 5.87, OR 3.70, 95% CI 1.56 - 10.18 and - OR 2.16, 95% 1.11 - 4.19, respectively). CONCLUSIONS: This prevention bundle successfully decreased SSIs in patients undergoing gynecologic cancer surgery. We recommend improving quality of care by wide implementation of SSI prevention bundles in Gynecologic Oncology patients.

Impact of adjuvant treatment on outcome in high-risk early-stage endometrial cancer: a retrospective three-center study.

OBJECTIVE: High grade and non-endometrioid endometrial cancers carry a poor prognosis, and the lack of randomized prospective data has led to a wide range of practice regarding adjuvant therapy. The objective of this study was to evaluate the outcomes of different treatment strategies in patients with high-risk, early-stage endometrial cancer. METHODS: Patients with high-grade endometrioid, serous endometrial cancer and carcinosarcoma diagnosed between 2000 and 2012 were identified from databases in three gynecologic oncology divisions, in Toronto and in Israel. Adjuvant treatment practices differed across the centers, creating a heterogeneous cohort. A comparison of stage I patients stratified by adjuvant treatment was undertaken. Log-rank tests and Cox proportional hazards models were employed to compare recurrence and survival across treatment groups. RESULTS: 490patients with high risk endometrial cancer were identified, among them 213 patients with stage I disease. Israeli patients received more chemotherapy (41% vs 10% in stage I disease; P<0.001) than patients in Toronto. Chemotherapy was not associated with improved disease-free, disease-specific or overall survival, nor was it associated with fewer distant recurrences (50% vs 54%). Radiation was also not associated with improved recurrence or survival, nor did it affect the pattern of recurrence. On Cox multivariable analysis, neither radiation treatment nor chemotherapy were significantly associated with outcome (HR for recurrence, 0.72 for pelvic radiation (P=0.46) and 1.99 for chemotherapy (P=0.09); HR for death, 0.67 for pelvic radiation (P=0.29) and 1.03 for chemotherapy (P=0.94)). CONCLUSIONS: In this retrospective analysis, neither adjuvant radiation nor chemotherapy were associated with improved outcome in stage I, high risk endometrial cancer.

Ovarian Yolk Sac Tumors; Does Age Matter?

BACKGROUND: Whereas among pediatric oncologists, ovarian yolk sac tumor (O-YST) is considered a chemosensitive tumor, it is often cited as an adverse prognostic factor in adult women with ovarian germ cell tumors. METHODS: The Malignant Germ Cell International Consortium data set included 6 pediatric clinical trials (United States, United Kingdom, and France) and 2 adult gynecology clinical trials (United States). Any patient with an O-YST that was International Federation of Gynecology and Obstetrics stage IC or higher and treated with a platinum-based chemotherapy was eligible. Age was modeled as a continuous and a categorical variable (children, 0-10 years; adolescents, 11-17 years; and adults, ≥18 years). In addition, analyses to establish the optimal cut point for age were conducted. Tumors were coded as pure YST (YST +/- teratoma), mixed YST (YST + other malignant germ cell component), or putative YST ("mixed" germ cell tumor + alpha-fetoprotein >1000 ng/mL). Histology, stage (II/III vs IV), preoperative alpha-fetoprotein levels (<1000; 1000-10,000, or >10,000 ng/mL), and chemotherapeutic regimen (carboplatin vs cisplatin) were analyzed as covariates. RESULTS: Two hundred fifty-one patients (median age, 13 years; range, 0-38 years) were identified (78 children, 139 adolescents, and 34 adults). Histology was pure, mixed, and putative in 129, 56, and 66 cases, respectively. Twenty-six patients had stage IV disease, similarly distributed in the 3 age groups. Median follow-up was 5.8 years. The overall 5-year event-free survival and overall survival was 91% (95% confidence interval, 87%-94%) and 96% (92%-98%), respectively. Age did not affect risk of event or death, modeled either as a categorical or continuous variable. Analysis failed to identify an age cut point that affected risk. None of the other covariates investigated had a prognostic impact on event-free survival or overall survival. CONCLUSIONS: Ovarian yolk sac tumors have an excellent outcome across all age-groups. Age has no apparent impact on the probability of event or death, allowing pediatric and gynecologic oncologists to enroll patients onto joint pediatric and adult trials.

Implementing a Cervical Sentinel Lymph Node Biopsy Program: Quality Improvement in Gynaecologic Oncology.

OBJECTIVE: Sentinel lymph node (SLN) biopsy is becoming a reasonable alternative to pelvic lymphadenectomy in early-stage cervical cancer. It is therefore imperative that centres without prior experience are able to successfully implement the procedure. The objectives of the current study were to (1) describe the process of implementing an SLN biopsy program with a novel peer mentorship component and (2) assess post-program quality improvement metrics, including SLN detection rate (DR) and diagnostic parameters. METHODS: An institutional SLN biopsy protocol was developed collaboratively by gynaecologic oncology, nuclear medicine, and pathology departments at University Health Network, Toronto, Ontario. All decisions were based on the best evidence available. Newly diagnosed, early-stage cervical cancer patients undergoing primary surgery were then recruited prospectively for SLN biopsy with combined technique, followed by pelvic lymphadenectomy to evaluate key quality indicators, including SLN DR, sensitivity, and negative predictive value. Surgeons with previous SLN biopsy experience mentored surgeons unfamiliar with the technique. Interim analyses and multidisciplinary rounds were regularly carried out to identify failures of technique or protocol. RESULTS: Thirty-nine patients (median age 42) were enrolled in the study between August 2010 and February 2014. The median number of SLNs and total pelvic lymph nodes removed per patient were 3 and 19, respectively. SLN DRs were 92% per patient (36/39), 88.5% per hemipelvis (69/78), and 85% bilaterally (33/39). SLN biopsy correctly identified seven of eight hemipelvises with nodal metastases, yielding a sensitivity of 88% (95% CI 0.47 to 1.00) and a false negative rate of 12% (95% CI 0 to 0.53). Surgeons undergoing peer mentorship (n = 3) performed as effectively (DR 100%) as surgeons (n = 2) with prior experience (DR 85%). CONCLUSIONS: This study provides a model upon which other centres can adopt and validate cervical SLN biopsy. High SLN DRs and accurate identification of lymph node metastases can be achieved by focusing on multidisciplinary collaboration, knowledge translation with creation of evidence-based protocols, peer mentorship, and ongoing quality control.

Cost-effectiveness of sentinel node biopsy and pathological ultrastaging in patients with early-stage cervical cancer.

BACKGROUND: The objective of this study was to determine the cost-effectiveness of radical hysterectomy (RH) and sentinel lymph node biopsy (SLNB) for the management of early-stage cervical cancer (stage IA2-IB1). METHODS: A simple decision tree model was developed to follow a simulated cohort of patients with early-stage cervical cancer treated with RH and 1 of 3 lymph node assessment strategies: systematic pelvic lymph node dissection (PLND), SLNB using technetium 99 (Tc99) and blue dye, and SLNB using Tc99 only. SLNB using indocyanine green (ICG) was used as an exploratory strategy. Relevant studies were identified to extract the probability data and utility parameters and to estimate quality-adjusted life-years (QALYs) and absolute life-years (ALYs). Only direct medical costs were modeled, and the time horizon for the study was 5 years. RESULTS: SLNB using Tc99 and blue dye cost $21,089 and yielded 4.54 QALYs and 4.90 ALYs. PLND cost $22,353 and yielded 4.47 QALYs and 4.91 ALYs. SLNB using blue dye and Tc99 was the most cost-effective strategy when ALYs were considered with an incremental cost-effectiveness ratio (ICER) of $144,531. When QALYs were considered, the SLNB technique using Tc99 and blue dye dominated all other strategies. SLNB using ICG cost $20,624 and yielded 4.90 ALYs and 4.54 QALYs. It was clinically superior to and less expensive than all other strategies when QALYs were the outcome of interest and had an ICER of $221,171 per ALY in comparison with RH plus PLND. CONCLUSIONS: SLNB using Tc99 and blue dye with ultrastaging is considered the most cost-effective strategy with respect to 5-year progression-free survival and morbidity-free survival. Although it was included only as an exploratory strategy in this study, SLNB with ICG has the potential to be the most cost-effective strategy. Cancer 2017;123:1751-1759. © 2017 American Cancer Society.

The Added Value of Pathology Review in Vulvar Cancer: Results From a Population-based Cohort Study.

We conducted a population-based patterns of care study of vulvar carcinoma. This paper describes the changes in reporting based on pathology review. This is a retrospective population-based cohort study. We obtained all pathology records available from the provincial cancer registry for primary invasive squamous cell carcinoma of the vulva diagnosed between 1998 and 2007. Pathology reviews were conducted centrally by a group of gynecologic pathologists and were identified during abstraction. Corresponding original reports were matched to pathology review reports based on accession numbers. We compared the reported value for presence/absence of invasion, grade, depth, thickness, size, lymphovascular space invasion, peripheral margin status, and deep margin status in the original and review report. A total of 1011 vulvar resection reports were identified. From these, we identified 316 pairs of original/review reports. Missing data were common but improved in the reviews. In total, 55 (17%) reports had at least 1 change from the original to the review based on presence of invasion, depth, lymphovascular space invasion, or margin. When we included reports where a variable was missing in the original but then completed in the review, there were clinically relevant changes in 210 reports (66%). Vulvar carcinoma is a rare diagnosis and pathology reviews resulted in potentially important clinical changes in a significant proportion of cases. Referral pathologists play an important role in contributing to high-quality clinical decisions.

Cervix Cancer Research Network (CCRN): Improving Access to Cervix Cancer Trials on a Global Scale.

Eighty-seven percent of cervix cancer occurs in less-developed regions of the world, and there is up to an 18-fold difference in mortality rate for cervix cancer depending on the region of the world. The Cervix Cancer Research Network (CCRN) was founded through the Gynecologic Cancer InterGroup with the aim of improving access to clinical trials in cervix cancer worldwide, and in so doing improving standards of care. The CCRN recently held its first international educational symposium in Bangkok. Sixty-two participants attended from 16 different countries including Pakistan, India, Bangladesh, Thailand, Malaysia, Singapore, Philippines, Taiwan, China, Vietnam, Korea, Japan, Columbia, Brazil, Canada, and the United States. The focus of this symposium was to evaluate progress, to promote new clinical trials for the CCRN, and to provide education regarding the role of brachytherapy in the treatment of cervical cancer.

Sentinel lymph node biopsy in vulvar cancer: Systematic review, meta-analysis and guideline recommendations.

OBJECTIVES: Traditionally, treatment for early stage vulvar cancer has included removal of the primary tumor and inguinofemoral lymph node dissection (IFLD). Sentinel lymph node biopsy (SLNB) has been proposed as an alternative to IFLD for early stage vulvar cancer patients. The aim of this project was to systematically review and assess the potential for harms and benefits with the SLNB procedure in order to make recommendations regarding the adoption of the procedure, selection of patients and appropriate technique and procedures. METHODS: A working group with expertise in gynecologic oncology and health research methodology was formed to lead the systematic review and process of guideline development. MEDLINE, Embase and The Cochrane Database of Systematic Reviews were searched for relevant articles published up to September 2014. Outcomes of interest included detection, false negative, complication and recurrence rates and indicators related to pathology. Meta-analyses were conducted where appropriate. RESULTS: The evidence-base of a previously published health technology assessment was adopted. An additional search to update the HTA's evidence base located three systematic reviews, and eleven individual studies that met the inclusion criteria. According to a meta-analysis, per groin detection rate for SLNB using radiocolloid tracer and blue dye was 87% [82-92]. The false negative rate with SLNB was 6.4% [4.4-8.8], and the recurrence rates with SLNB and IFLD were 2.8% [1.5-4.4] and 1.4% [0.5-2.6], respectively. An internal and external review process elicited concerns about the necessity of performing this procedure in an appropriate organizational context. CONCLUSION: SLNB is recommended for women with unifocal tumors<4 cm and clinically non-suspicious nodes in the groin, provided that specific infrastructure and human resource needs are met. Some recommendations for appropriate techniques and procedures are also provided.

Sentinel lymph node biopsy in vulvar cancer: a health technology assessment for the canadian health care context.

OBJECTIVES: Inguinofemoral lymphadenectomy for vulvar cancer is associated with a high incidence of groin wound complications and lymphedema. Sentinel lymph node biopsy (SLNB) is a morbidity-reducing alternative to lymphadenectomy. The objective of this health technology assessment was to determine the clinical effectiveness, cost-effectiveness, and organizational feasibility of SLNB in the Canadian health care system. METHODS: A review of the English-language literature published from January 1992 to October 2011 was performed across five databases and six grey-literature sources. Predetermined eligibility criteria were used to select studies, and results in the clinical, economic, and organizational domains were summarized. Included studies were evaluated for methodologic quality using the Newcastle-Ottawa Scale. RESULTS: Of 825 reports identified, 88 observational studies met the eligibility criteria. Overall study quality was poor, with a median Newcastle-Ottawa Scale score of 2 out of 9 stars. Across all studies, the detection rate of the sentinel lymph node was 82.2% per groin and the false-negative rate was 6.3%. The groin recurrence rate after negative SLNB was 3.6% compared with 4.3% after negative lymphadenectomy, and complications were reduced after SLNB. No economic evaluations were identified comparing SLNB to lymphadenectomy. Safe implementation of SLNB requires appropriate patient selection, detection technique, and attention to the learning curve. CONCLUSIONS: Although study quality is poor, the available data suggest implementation of SLNB may be safe and feasible in Canadian centres with adequate procedural volumes, assuming that implementation includes careful patient selection, careful technique, and ongoing quality assessment. Cost-effectiveness has yet to be determined.

Phase II trial of the histone deacetylase inhibitor belinostat in women with platinum resistant epithelial ovarian cancer and micropapillary (LMP) ovarian tumours.

AIM: Micropapillary/borderline (LMP) ovarian tumours are rarely included in clinical trials and are intrinsically resistant to radiation and chemotherapy. Platinum resistant epithelial ovarian cancer (EOC) has a poor prognosis. The histone deacetylase inhibitor belinostat demonstrated antitumour activity in pre-clinical ovarian cancer models. METHODS: A phase II study was performed to evaluate the activity of belinostat in two patient populations: women with metastatic or recurrent platinum resistant (progression within 6 months) EOC and LMP ovarian tumours, both groups had received no more than 3 prior lines of chemotherapy. Belinostat 1000 mg/m(2)/d was administered iv days 1-5 of a 21 d cycle. Peripheral blood mononuclear cells (PBMCs) and tumour biopsies, where possible, for correlative studies were obtained prior to and following treatment. RESULTS: Eighteen patients with EOC and 14 patients with LMP tumours were enrolled on study. Belinostat was well tolerated with no grade four toxicity (179 cycles). Grade 3 toxicity consisted of thrombosis (3 patients), hypersensitivity (1) and elevated ALP (1). One patient with LMP tumour had a partial response (unconfirmed) and 10 had stable disease (SD), 3 were non-evaluable. Median progression-free survival (PFS) was 13.4 months (95% confidence interval (CI), 5.6--not reached). Best response in patients with EOC was SD (nine patients) and median PFS was 2.3 months (95% CI, 1.2-5.7 months). An accumulation of acetylated histones H3 and H4 was noted in PBMCs and in tumour tissue. CONCLUSIONS: Belinostat is well tolerated in both patient groups and shows some activity in patients with micropapillary (LMP) disease.