Benefits of the Enhanced Recovery After Surgery (ERAS) Pathway With Quadratus Lumborum Blocks for Minimally Invasive Gynecologic Surgery Patients: A Retrospective Cohort Study.

STUDY OBJECTIVE: This study aimed to determine the effect of the implementation of the Enhanced Recovery After Surgery (ERAS) protocol among patients receiving minimally invasive gynecologic surgery. DESIGN AND SETTING: This retrospective cohort study was performed in a tertiary care hospital. PATIENTS: A total of 328 females who underwent minimally invasive gynecologic surgeries requiring at least one overnight stay at Keck Hospital of University of Southern California (USC), California, USA, from 2016 to 2020 were included in this study. INTERVENTIONS: The institutional ERAS protocol was implemented in late 2018. A total of 186 patients from 2016 to 2018 prior to the implementation were compared to 142 patients from 2018 to 2020 after the implementation. Intraoperatively, the ERAS group received a multimodal analgesic regimen (including bilateral quadratus lumborum (QL) blocks) and postoperative care geared toward a satisfactory, safe, and expeditious discharge. MEASUREMENTS AND MAIN RESULTS: The two groups were similar in demographics, except for the shorter surgical time noted in the ERAS group. The median opioid use was significantly less among the ERAS patients compared with the non-ERAS patients on postoperative day 1 (7.5 vs. 14.3 mg; p<0.001) and throughout the hospital stay (17.4 vs. 36.2 mg; p<0.001). The ERAS group also had a shorter median hospital length of stay compared to the non-ERAS group (p<0.01). Among patients with a malignant diagnosis, patients in the ERAS group had significantly less postoperative day 1 and total opioid use and a shorter hospital stay (p<0.01). Within the ERAS group, 20% of the patients did not end up receiving a QL block. Opioid use and length of stay were similar between patients who did and did not receive the QL block. CONCLUSIONS: The ERAS pathway was associated with a reduction in opioid use postoperatively and a shorter length of hospital stay after minimally invasive gynecologic surgery. There was a more significant decrease in opioid use and hospital length of stay for patients with malignant diagnoses compared to patients with benign diagnoses. Further research can be done to fully delineate the effect of QL blocks in ERAS protocols.

Population-level uptake of neoadjuvant chemotherapy for stage IVB endometrial cancer.

OBJECTIVE: To examine population-level trends, characteristics, and outcomes of patients with stage IVB endometrial cancer who received neoadjuvant chemotherapy (NACT) prior to surgery. METHODS: The National Cancer Institute's Surveillance, Epidemiology, and End Results Program was retrospectively queried by examining 5505 patients with stage IVB endometrial cancer from 2010 to 2018. Exposure allocation was per treatment: primary surgery followed by chemotherapy (n = 3052, 55.4%), NACT followed by surgery (n = 930, 16.9%), and chemotherapy alone (n = 1523, 27.7%). Main outcomes measured were (i) the trend of utilization of NACT and patient characteristics related to NACT assessed with multinomial regression analysis and (ii) overall survival (OS) assessed with multivariable Cox proportional hazards regression model. RESULTS: The number of patients receiving NACT prior to surgery increased from 11.6% to 21.7% whereas those undergoing primary surgery followed by chemotherapy decreased from 62.7% to 48.3% (P < 0.001). Increasing utilization of NACT remained independent in multivariable analysis (adjusted-odds ratio per one-year increments 1.11, 95% confidence interval [CI] 1.08-1.15). Increasing utilization of NACT was observed in several sub-cohorts including patients aged <65 years, ≥65 years, White, non-White, endometrioid, non-endometrioid, and cases with non-distant organ metastasis (P < 0.05). In a multivariable analysis, NACT followed by surgery and primary surgery followed by chemotherapy had comparable OS (median 25 versus 26 months, adjusted-hazard ratio [HR] 1.03, 95%CI 0.93-1.15). When examined for metastatic extent, NACT followed by surgery was associated with decreased OS compared to primary surgery followed by chemotherapy in the non-distant organ metastasis group (adjusted-HR 1.20, 95%CI 1.05-1.36) whereas it was associated with improved OS in the distant organ metastasis group (adjusted-HR 0.79, 95%CI 0.66-0.95). CONCLUSION: The treatment of stage IVB endometrial cancer is shifting from primary surgery to NACT in the United States.

Side-to-end reanastomosis after low-anterior resection (STELAR): Outcomes, feasibility, and description of procedure performed by a gynecologic oncology service.

BACKGROUND AND OBJECTIVES: Low anterior rectosigmoid resection for a gynecologic disease is usually performed in concert with other procedures and can result in significant morbidity should anastomotic complication occur. This study examined surgical outcomes of side-to-end reanastomosis after low anterior resection (STELAR) performed by gynecologic oncology service. METHODS: This is a case series examining consecutive patients who underwent STELAR for gynecologic indications by a single gynecologic oncology group from 2009 to 2018. Prospectively collected institutional surgical database was searched for STELAR, and standard descriptive statistics were used to describe intraoperative and postoperative complications specific to reanastomosis. RESULTS: A total of 69 women underwent STELAR, with median age and body mass index of 54 years and 24 kg/m2 , respectively. 63.8% of patients had ovarian cancer and 84.4% had stage III-IV disease. The median estimated blood loss was 875 ml. Four (5.8%) women underwent protective loop colostomy at the time of STELAR. Postoperatively, there was 1 (1.4%) case of abscess formation within 30 days and 1 (1.4%) case of anastomotic leak 5 weeks after STELAR that required reoperation and diversion. No cases of fistula were clinically identified. CONCLUSION: Side-to-end reanastomosis may be a safe and feasible procedure to accomplish low rectosigmoid anastomosis in women with gynecologic disease.

Characterizing isolated tumor cells in regional lymph nodes of early endometrial cancer.

OBJECTIVE: To examine the characteristics of isolated tumor cells (ITCs) in regional lymph nodes of early-stage endometrial cancer. METHODS: This is a retrospective cohort study examining the National Cancer Institute's Surveillance, Epidemiology, and End Result Program. The study population was 6472 women with non-metastatic, node-negative T1 endometrial cancer who underwent primary hysterectomy and surgical nodal evaluation. Multivariable binary logistic regression model was used to identify the independent characteristics for ITCs. Postoperative therapy according to ITCs status was also assessed with propensity score weighting. RESULTS: ITCs were seen in 111 (1.7%) cases. In a multivariable analysis, ITCs were largely associated with tumor factors including deep myometrial invasion (T1b versus T1a, 4.0% versus 1.0%, adjusted-odds ratio [aOR] 3.42, P < 0.001) and larger tumor size (>4 versus ≤4 cm, 3.0% versus 1.6%, aOR 1.55, P = 0.037). Moreover, women undergoing sentinel lymph node (SLN) biopsy had a higher likelihood of identifying ITCs compared to those undergoing lymphadenectomy (LND): 2.7% for SLN alone, 3.7% for SLN/LND, and 1.2% for LND alone (aOR ranged 2.60-2.99, P < 0.001). Women who had ITCs identified were more likely to receive postoperative therapy (81.8% versus 31.7%, P < 0.001), including external beam radiotherapy (EBT) alone (25.1% versus 3.2%) and chemotherapy/EBT (16.3% versus 1.9%). Similar associations were observed in the low-risk group (stage IA, grade 1-2 endometrioid, 78.4% versus 9.2%, P < 0.001), including EBT alone (35.3% versus 0.6%). CONCLUSION: This study suggests that a SLN protocol can identify more ITCs in the regional lymph nodes of early endometrial cancer. Deep myometrial invasion and large tumor size were associated with increased risk of ITCs. Postoperative therapy is offered more frequently in the setting of ITCs with variable treatment patterns, warranting further outcome studies and practice guidelines.

Population-level trends and outcomes of sentinel lymph node biopsy in vulvar cancer surgery in the United States.

OBJECTIVE: To examine population-level trends, characteristics, and outcomes related to nodal assessment for vulvar cancer surgery in the United States. METHODS: This is a retrospective cohort study querying the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. The study population was 5604 women with T1b or T2-smaller(≤4 cm) squamous cell carcinoma of the vulva who underwent primary vulvectomy from 2003 to 2018. The exposure allocation was based on nodal evaluation type: lymphadenectomy (LND; n = 3319, 59.2%), sentinel lymph node (SLN) biopsy (n = 751, 13.4%), or no surgical nodal evaluation (n = 1534, 27.4%). The main outcomes were (i) trends and characteristics related to SLN biopsy assessed by multinomial regression model, and (ii) vulvar cancer-specific survival assessed by competing risk analysis and inverse probability of treatment weighting propensity score. Sensitivity analysis included evaluation of external cohort with T1a disease (n = 1291). RESULTS: The utilization of SLN biopsy increased from 5.7% to 23.3% in 2006-2018, while the proportion of LND decreased from 64.1% to 48.8% in 2010-2018, and these associations remained independent in multivariable analysis (adjusted-P < 0.05). In the propensity score weighted model, 5-year cumulative rate for vulvar cancer-specific mortality was 15.2% (interquartile range 12.1-18.9) for the SLN biopsy group and 16.9% (interquartile range 15.6-18.3) for the LND group (subdistribution-hazard ratio 0.90, 95% confidence interval 0.76-1.06, P = 0.217). The increasing SLN biopsy use was also observed in T1a disease from 1.3% to 7.3% during the study period (P < 0.001). CONCLUSION: The landscape of surgical nodal evaluation is shifting from lymphadenectomy to SLN biopsy in vulvar cancer surgery in the United States. SLN biopsy-incorporated treatment approach was not associated with worse survival compared to LND.

Incorporation of vaginal brachytherapy to external beam radiotherapy in adjuvant therapy for high-risk early-stage cervical cancer: A comparative study.

PURPOSE: To examine trends, characteristics, and outcomes related to addition of vaginal brachytherapy (VBT) to external beam radiotherapy (EBRT) for adjuvant radiotherapy in high-risk early-stage cervical cancer. METHODS AND MATERIALS: This comparative study is a retrospective observational analysis of the National Cancer Institutes' Surveillance, Epidemiology, and End Results Program. Surgically treated women with stage T1-2 cervical cancer who had high-risk factors (nodal metastasis and/or parametrial invasion) and received adjuvant radiotherapy from 2000 to 2018 were examined. Propensity score inverse probability of treatment weighting was used to assess the survival estimates for addition of VBT use. RESULTS: Among 2470 women with high-risk factors receiving EBRT, 760 (30.8%) had additional VBT. During the study period, there was an increasing trend of VBT use from 27.4% to 36.1% (p< 0.001). In a multivariable analysis, year of diagnosis and high-risk tumor factors: parametrial involvement, large tumor size, and use of chemotherapy remained independent characteristics associated with VBT use (all, p< 0.05). In propensity score-weighted models, VBT use with EBRT and EBRT alone had comparable overall survival (5-year rates 73.8% vs. 77.4%, hazard ratio [HR] 1.07, 95% confidence interval [CI] 0.92-1.25). Nonsignificant association was also observed in squamous or nonsquamous tumors, young or old age, low or high nodal ratio, chemotherapy use, and simple or radical hysterectomy (all, p> 0.05). Lastly, the addition of VBT was not associated with cervical cancer-specific survival (subdistribution-HR 1.15, 95% CI 0.94-1.41). CONCLUSIONS: Utilization of VBT with EBRT for adjuvant radiotherapy in high-risk early-stage cervical cancer is increasing in the United States. Addition of VBT was associated with neither overall survival nor cancer-specific survival.

Adjuvant hysterectomy following primary chemoradiation for stage IB2 and IIA2 cervical cancer: a retrospective comparison of complications for open versus minimally invasive surgery.

BACKGROUND: Adjuvant hysterectomy following chemoradiation for bulky, early stage cervical cancer has been shown to decrease local relapse rate. The objective of this study is to compare complications and recurrences between minimally invasive and open adjuvant hysterectomy for early stage cervical cancer. METHODS: Patients were identified who had undergone adjuvant hysterectomy following chemoradiation for 2009 FIGO stage IB2 and IIA2 cervical cancer from August 2006 to June 2018. Demographic information, treatment course, complications, recurrence data were retrospectively extracted from the medical record. Frequency of complications was compared with Fisher exact test or chi-square test as appropriate and inverse probability of treatment propensity score weighting was used to calculate the disease-free survival. RESULTS: Fifty-four patients met inclusion criteria with a median follow up time of 60.4 months (interquartile range 28.0-98.1 months). There were 24 (44%) open versus 30 (56%) minimally invasive hysterectomies performed. The overall grade 2 or worse complication rate was 43%. There were 8 (27%) patients with complications in the minimally invasive group compared to 4 (17%) in the open group (OR 1.82 (95% CI 0.5-7.0)). There were 9 vaginal cuff defects, dehiscences and/or fistulas in the minimally invasive group compared to 3 in the open group (OR 3.0 (95% CI 0.8-11.2)). There was no statistically significant difference between disease free survival and overall survival among the two groups, however there was a trend towards decreased disease-free survival in the minimally invasive group. CONCLUSIONS: Among women undergoing adjuvant hysterectomy following chemoradiation for bulky, early stage cervical cancer, there was no difference in complication rates between an open or minimally invasive surgical approach. However, the overall complication rate was high, including a high rate of vaginal cuff defect, dehiscence and/or fistulas. Our findings suggest that an adjuvant hysterectomy should be reserved for patients in which chemoradiation is not anticipated to successfully treat the primary tumor and, if performed, an open approach should be considered.

Borderline Brenner Tumor of the Ovary Coexisting With an Ovarian Mucinous Cystadenoma With Focal Atypical Epithelial Proliferation: A Rare Case With Review of the Literature.

Ovarian Brenner tumors, accounting for ∼5% of overall ovarian epithelial neoplasm, are often reported in association with mucinous neoplasm. Histogenetically, the two tumors are thought to arise from similar precursors. To date, fewer than 60 borderline Brenner tumors alone have been reported, and the concomitant presence of atypical proliferative components in Brenner and mucinous tumors is even rarer. Therefore, the clinicopathological characteristics and prognosis of patients with the borderline Brenner tumors alone or coexisting with mucinous neoplasm are extremely limited. Herein, we report a unique case of a 53-year-old woman with a unilateral ovarian borderline Brenner tumor associated with focal atypical mucinous epithelial proliferation and her clinical presentations. The clinicopathological features of the tumor are documented and the literature review along with the clinical molecular advances are summarized in this study.

Recurrence Rates in Patients With Cervical Cancer Treated With Abdominal Versus Minimally Invasive Radical Hysterectomy: A Multi-Institutional Retrospective Review Study.

PURPOSE: To compare the disease-free survival (DFS) between open and minimally invasive radical hysterectomies (RH) performed in academic medical institutions. METHODS: Retrospective multi-institutional review of patients undergoing RH for stage IA1 (with lymphovascular invasion), IA2, and IB1 squamous, adenocarcinoma, or adenosquamous carcinoma between January 1, 2010 and December 31, 2017. RESULTS: Of 815 patients, open RH was performed in 255 cases (29.1%) and minimally invasive RH in 560 cases (70.9%). There were 19 (7.5%) recurrences in the open RH and 51 (9.1%) recurrences in the minimally invasive group (P = .43). Risk-adjusted analysis revealed that minimally invasive RH was independently associated with an increased hazard of recurrence (aHR, 1.88; 95% CI, 1.04 to 3.25). Other factors independently associated with an increased hazard of recurrence included tumor size, grade, and adjuvant radiation. Conization before surgery was associated with lower recurrence risk (aHR, 0.4; 95% CI, 0.23 to 0.71). There was no difference in OS in the unadjusted analysis (HR, 1.14; 95% CI, 0.61 to 2.11) or after risk adjustment (aHR, 1.01; 95% CI, 0.5 to 2.2). Of 264 patients with tumors ≤ 2 cm on final pathology (excluding those with no residual tumor on final pathology), 2/82 (2.4%) recurred in the open RH group and 16/182 (8.8%) in the minimally invasive RH group (P = .058). In propensity score matching analysis, 7/159 (4.4%) recurrences were noted in the open RH group and 18/156 (11.5%) in the minimally invasive RH group (P = .019). Survival analysis revealed an increased risk of recurrence in the minimally invasive group in propensity-matched cohort (HR, 2.83; 95% CI, 1.1 to 7.18). CONCLUSION: In this retrospective series, patients undergoing minimally invasive radical hysterectomy, including those with tumor size ≤ 2 cm on final pathology, had inferior DFS but not overall survival in the entire cohort.

Non-prescription cannabis use for symptom management amongst women with gynecologic malignancies.

OBJECTIVES: To evaluate interest in and patterns of use of non-prescription cannabis products for symptom management amongst gynecologic cancer patients living in states with legal access to medical and recreational marijuana. METHODS: Cross-sectional study using a novel 35-question survey distributed to women diagnosed with gynecologic cancer within two academic centers in California and Colorado. The survey queries demographic and disease traits, and both objective and subjective issues surrounding use of cannabis products for symptom management. Surveys were distributed to patients actively receiving treatment or under surveillance. RESULTS: Enrollment began July 16, 2018 and was completed December 1, 2018. Survey return rate was 52.7%. A total of 225 participants met inclusion criteria.Sixty-two percent reported that they have used or would be interested in using cannabis products for symptom management; 60 (26.7%) are using non-prescription cannabis for treatment of cancer related symptoms, and 80 (35.6%) are interested in using cannabis derivatives under direction of their oncologist. Reasons cited for use of cannabis included: pain control (n = 41, 68.3), insomnia (n = 33, 55.0%), anxiety (n = 29, 48.3%), nausea (n = 26, 43.3%), and appetite stimulation (n = 21, 35.0%). Of the women using cannabis products, almost half report decreased prescription narcotic use after initiation of cannabis products (n = 27, 45.0%). CONCLUSIONS: Women with gynecologic cancer report a strong interest in the use of non-prescription cannabis products for management of cancer-related symptoms. Practitioners in the field of gynecologic oncology should be aware of the frequency of use of non-prescription cannabis amongst their patients as well as the growing desire for guidance about the use of cannabis derivatives. A substantial number of patients report decreased reliance on opioids when using cannabis derivatives for pain control.

Paraneoplastic Cushing's syndrome and hypercalcemia arising from metastatic endometrioid endometrial adenocarcinoma: A case report.

•Paraneoplastic Cushing's syndrome is rarely seen in gynecologic cancers, appearing only in case reports•It almost universally results in acute decompensation and portends a poor prognosis•We describe a patient with metastatic endometrial carcinoma with both paraneoplastic Cushing's syndrome and hypercalcemia•High clinical suspicion for malignancy is essential, as these syndromes improve with treatment of the underlying malignancy.

Validity and prognostic significance of sperm protein 17 as a tumor biomarker for epithelial ovarian cancer: a retrospective study.

BACKGROUND: Prior small studies have shown increased expression of sperm protein 17 (Sp17) in epithelial ovarian cancer (EOC) tissue and suggest Sp17 as a potential biomarker for EOC. However, how Sp17 expression varies with histology, grade, and stage of EOC and its expression in other ovarian neoplasms has not been defined. It is unknown whether patients with EOC have elevated serum Sp17 levels or if Sp17 expression is associated with survival outcomes. METHODS: The study included 982 patients with benign, borderline, and malignant ovarian neoplasms and normal ovary. There were 878 patients with tissue only, 39 with serum only, and 65 with matching serum and tissue. Immunohistochemical (IHC) staining with anti-Sp17 antibody was performed on tissue specimens and the intensity scored as weak, moderate, or strong. A sandwich enzyme-linked immunosorbent assay (ELISA) was performed to measure Sp17 sera concentrations. RESULTS: Sp17 expression was most commonly seen in serous cystadenomas (83%) and serous borderline tumors (100%). Of the 773 EOC specimens, 223 (30%) expressed Sp17. Grade and histology were significantly associated with Sp17 expression among EOC specimens (p < 0.001) on both univariate and multivariable analysis, with grade 1 serous adenocarcinomas showing the highest expression (51%). Sp17 expression was limited in other benign and non-epithelial malignant neoplasms. Neither Sp17 tissue expression nor serum concentration correlated with survival outcomes. Serum concentrations were higher in patients with Sp17 tissue expression, and the highest concentrations were noted among patients with serous and clear cell adenocarcinomas. CONCLUSIONS: Sp17 is highly expressed in benign, borderline, and low grade malignant serous ovarian neoplasms and can be quantified in serum. Sp17 expression may have diagnostic significance in this subset of patients.

Predictive Value of FDG PET/CT to Detect Lymph Node Metastases in Cervical Cancer.

PURPOSE: The aim of this study was to determine the prognostic significance of PET/CT findings in women with cervical cancer and describe the normalization of lymph node SUVmax (nSUVmax). MATERIALS AND METHODS: A retrospective review was performed of 113 patients with cervical cancer who underwent a PET/CT before receiving definitive therapy. SUVmax measurements were normalized to the SUV of the pelvic blood pool. Patient, tumor, and PET/CT data were correlated to extracervical recurrence-free survival (ecRFS) and lymph node pathology. RESULTS: Of 113 patients, there were 23 (20%) extracervical recurrences. On univariate analysis, stage, histology, nSUVmax, and radiographic size of the primary tumor, and nSUVmax of the most hypermetabolic lymph node were significantly associated with ecRFS. On multivariable analysis, nSUVmax and radiographic size of the primary tumor remained associated with ecRFS (both P < 0.001). Sixty-six patients underwent pelvic, common iliac, and/or para-aortic nodal sampling. The sensitivity, specificity, false-negative, and false-positive rates of PET/CT for lymph node metastases were 53%, 75%, 6%, and 82%, respectively. On univariate analysis, nSUVmax, and radiographic size of the primary tumor, and nSUVmax of the most hypermetabolic lymph node, and radiographic size of the largest lymph node, were associated with the presence of at least one pathologically positive lymph node. On multivariable analysis, only the radiographic size of the largest lymph node remained significantly associated with lymph node metastases (P < 0.001). CONCLUSIONS: The size and nSUVmax of the primary tumor were associated with ecRFS. PET/CT has a low false-negative rate but high false-positive rate for lymph node metastases.

Efficacy of Modified Dose-dense Paclitaxel in Recurrent Cervical Cancer.

OBJECTIVE: To examine survival outcomes of women with recurrent cervical cancer who received salvage chemotherapy with modified dose-dense paclitaxel (MDDP) monotherapy (paclitaxel 80 mg/m, administered on day 1, 8, and 15 without day 22). MATERIALS AND METHODS: A retrospective study was conducted to evaluate cause-specific survival after the first recurrence (SAR) of women with recurrent cervical cancer diagnosed between 2006 and 2014. Pooled analyses were performed to examine SAR in women who received MDDP monotherapy (n=17) for any treatment line, compared with those who received salvage chemotherapy with paclitaxel-doublet (n=18) and nonpaclitaxel regimens (n=52). RESULTS: In the whole cohort, median SAR was 13.7 months including 63 (72.4%) events. MDDP monotherapy regimen was most commonly used in the second-line setting (35.3%) followed by the third/fourth lines (both, 23.5%). Among the women who received MDDP regimen, there were 6 (35.3%) women who received ≥6 cycles; there was 1 (5.9%) women who discontinued the regimen due to adverse effects (grade 3 transaminitis); regimen postponement was seen in 2 (1.4%) of 140 total cycles; and the response rate after the sixth cycle of this regimen was 29.4% (1 complete and 4 partial responses). On univariate analysis, MDDP usage had the highest 2-year SAR rate (MDDP 54.1%, paclitaxel-doublet 43.6%, and nonpaclitaxel regimens 28.1%; Ptrend=0.044). On multivariate analysis, MDDP monotherapy remained an independent prognostic factor for improved SAR compared with the nonpaclitaxel regimen (adjusted-hazard ratio, 0.50; 95% confidence interval, 0.26-0.95; P=0.036). CONCLUSION: Our results suggested that MDDP monotherapy is a tolerable and relatively effective regimen for recurrent cervical cancer.

Association of Metformin Use and Survival Outcome in Women With Cervical Cancer.

OBJECTIVE: Although preclinical studies suggest possible antitumor effects of metformin against cervical cancer, there is currently a lack of clinical data examining the association of metformin use and survival in women with cervical cancer. The aim of this study was to examine survival of women with cervical cancer who were receiving metformin. METHODS: This is a retrospective study examining consecutive cases of stages I to IV cervical cancer between 2000 and 2014. Patient demographics, medication use, tumor characteristics, treatment patterns, and survival outcomes were correlated to metformin use. RESULTS: There were 70 (8.9%; 95% confidence interval [CI], 6.9-10.9) metformin users and 715 nonusers identified for the analysis. Median follow-up time was 22.6 months. Recurrence/progression of disease and death due to cervical cancer were observed in 236 and 163 cases, respectively. Metformin users were more likely to be older, hypertensive, diabetic, and dyslipidemic compared with nonusers (all, P < 0.05). On univariate analysis, metformin users and nonusers had similar progression-free survival (PFS) (5-year rates; 57.3% vs 61.8%; P = 0.82) and cervical cancer-specific overall survival (71.7% vs 70.7%; P = 0.86). After adjusting for patient demographics and tumor characteristics, metformin use was not associated with PFS (adjusted hazards ratio, 1.11; 95% CI, 0.70-1.74; P = 0.67) or cervical cancer-specific overall survival (adjusted hazards ratio, 0.91; 95% CI, 0.52-1.60; P = 0.75). Among 478 women who received whole pelvic radiotherapy, metformin use was not associated with PFS (P = 0.93) or cervical cancer-specific overall survival (P = 0.32). CONCLUSIONS: In this study population, metformin use was not associated with survival of women with cervical cancer.

Significance of venous thromboembolism in women with cervical cancer.

OBJECTIVE: To characterize risk factors of venous thromboembolism (VTE) and to examine effects of VTE on survival of women with cervical cancer. METHODS: This is a retrospective study examining consecutive stage I-IV cervical cancer cases diagnosed between 2000 and 2014. Cumulative risk of VTE after cervical cancer diagnosis was evaluated by a time-dependent analysis, expressing adjusted-hazard ratio [HR] and 95% confidence interval [CI]. Survival analysis was performed to determine independent risk factors for progression-free survival (PFS) and disease-specific overall survival (OS). RESULTS: VTE was recorded in 98 (12.3%, 95%CI 11.6-22.8) out of 798 cases with 1-, 2-, and 5-year cumulative incidences after cervical cancer diagnosis being 8.4%, 11.3%, and 18.7%, respectively. On multivariable analysis, advanced-stage disease (2-year cumulative risk, distant metastatic disease 44.8% [HR 4.13, 95%CI 1.06-10.7, P=0.003], and locally-advanced disease 13.4% [HR 2.46, 95%CI 1.17-4.43, P=0.004]) were independently associated with increased risk of VTE compared to early-stage disease (stage IA1-IB1 4.1%). In addition, low albumin level (HR per unit change, 0.59, 95%CI 0.40-0.85, P=0.005) and chemotherapy treatment (HR 2.46, 95%CI 1.30-4.66, P=0.006) remained independent risk factors associated with increased risk of VTE. On univariate analysis, VTE was significantly associated with decreased PFS (5-year rates, 22.3% versus 68.7%, P<0.001) and OS (5-year rates, 55.1% versus 90.0%, P<0.001). On multivariable analysis, VTE remained an independent prognostic factor associated with decreased PFS (HR 1.95, 95%CI 1.43-2.67, P<0.001) and OS (HR 3.54, 95%CI 2.04-6.13, P<0.001). CONCLUSION: VTE represents aggressive tumor behavior and poor patient condition, and is an independent prognostic factor for decreased survival in women with cervical cancer.