Clinical analysis of pathologic complete responders in advanced-stage ovarian cancer.

OBJECTIVE: To determine the clinical characteristics of patients who attained pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT) and to identify specific predictive or prognostic factors associated with pCR. METHODS: Two distinct populations of patients who underwent NACT followed by interval tumor reductive surgery (TRS) were used in this retrospective study. The first contained 472 patients from a single institution. The second contained only pCR patients (67); those identified from population one, plus 44 obtained through collaborative institutions. Cox analysis and log-rank tests were performed to assess associations between clinical characteristics and pCR outcome, recurrence-free survival (RFS), and overall survival (OS). RESULTS: The median RFS and OS in our pCR-only population was 24.2 and 80.8 months, respectively, with a median follow-up time of 32.4 months. In our single institution population, 23 patients attained pCR (4.9%) and had longer RFS compared to non-pCR patients with viable microscopic, optimal, or suboptimal residual disease (24.3 vs. 12.1 vs. 11.6 vs. 9.6 months, p = 0.025, 0.012, 0.008, respectively), and longer OS compared to those with optimal or suboptimal residual disease (54.5 vs. 29.4 vs. 25.7 months, p = 0.027, 0.007, respectively). Patients were more than three-fold likely to attain pCR if their CA125 value was normal at the time of surgery (OR 3.54, 95% CI: 1.14-11.05, p = 0.029). CONCLUSIONS: Women with pCR after NACT have significantly longer RFS compared to those with residual viable tumor at the time of interval tumor-reductive surgery, and CA125 is plausible biomarker for identifying these extreme responders preoperatively.

Prospective phase II trial of levonorgestrel intrauterine device: nonsurgical approach for complex atypical hyperplasia and early-stage endometrial cancer.

BACKGROUND: The incidence of complex atypical hyperplasia and early-stage endometrioid endometrial cancer is increasing, in part owing to the epidemic of obesity, which is a risk factor tightly linked to the development of endometrial hyperplasia and cancer. The standard upfront treatment for complex atypical hyperplasia and early-stage endometrial cancer is hysterectomy. However, nonsurgical treatment of early-stage endometrial neoplasia may be necessary owing to medical comorbidities precluding surgery or desired future fertility. OBJECTIVE: This study aimed to evaluate the efficacy of the levonorgestrel intrauterine device to treat complex atypical hyperplasia and grade 1 endometrioid endometrial carcinoma. STUDY DESIGN: A single-institution, single-arm, phase II study of the levonorgestrel intrauterine device (52 mg levonorgestrel, Mirena) was conducted in patients with complex atypical hyperplasia or grade 1 endometrioid endometrial cancer. The primary endpoint was pathologic response rate at 12 months, including complete or partial response. Quality of life and toxicity were assessed. Molecular analyses for proliferation markers, hormone-regulated genes, and wingless-related integration site pathway activation were performed at baseline and 3 months. RESULTS: A total of 57 patients were treated (21 endometrial cancer, 36 complex atypical hyperplasia). The median age was 48.0 years, and the median body mass index was 45.5 kg/m2. Of the 47 evaluable patients, 12-month response rate was 83% (90% credible interval, 72.7-90.3)-37 were complete responders (8 endometrial cancer; 29 complex atypical hyperplasia), 2 were partial responders (2 endometrial cancer), 3 had stable disease (2 endometrial cancer; 1 complex atypical hyperplasia), and 5 had progressive disease (3 endometrial cancer; 2 complex atypical hyperplasia). After stratification for histology, the response rate was 90.6% for complex atypical hyperplasia and 66.7% for grade 1 endometrioid endometrial cancer. Notably, 4 patients (9.5%) experienced relapse after the initial response. Adverse events were mild, primarily irregular bleeding and cramping. Quality of life was not negatively affected. At 3 months, exogenous progesterone effect was present in 96.9% of responders (31 of 32) vs 25% of nonresponders (2 of 8) (P=.001). Nonresponders had higher baseline proliferation (Ki67) and lower dickkopf homolog 3 gene expression than responders (P=.023 and P=.030). Nonresponders had significantly different changes in secreted frizzled-related protein 1, frizzled class receptor 8, and retinaldehyde dehydrogenase 2 compared with responders. CONCLUSION: The levonorgestrel intrauterine device has a substantial activity in complex atypical hyperplasia and grade 1 endometrioid endometrial cancer, with a modest proportion demonstrating upfront progesterone resistance. Potential biomarkers were identified that may correlate with resistance to therapy; further exploration is warranted.

The role of neoadjuvant chemotherapy in the management of low-grade serous carcinoma of the ovary and peritoneum: Further evidence of relative chemoresistance.

OBJECTIVE: Low-grade serous carcinoma of the ovary/peritoneum (LGSC) is relatively chemoresistant in the adjuvant, neoadjuvant, and recurrent settings. We sought to expand our prior work and evaluate response rates of women with LGSC to neoadjuvant chemotherapy (NACT) compared to women with high-grade serous carcinoma of the ovary/peritoneum (HGSC). METHODS: Thirty-six patients with LGSC who received NACT were matched to patients with HGSC. A single radiologist re-reviewed pre- and post-NACT imaging for response using RECIST 1.1. Pre- and post-NACT CA-125 values were compared using paired t-tests. Kaplan-Meier estimates of progression free survival (PFS) and overall survival (OS) were performed. RESULTS: All patients received neoadjuvant platinum-based regimens. LGSC patients received a median of 5 cycles (range 3-9), HGSC patients received a median of 4 cycles (range 3-9). Interval cytoreductive surgery was performed in 29/36 (81%) of LGSC and 32/36 (89%) HGSC patients. Complete cytoreduction was reported and achieved in 11/29 (38%) of LGSC patients and 24/32 (75%) of HGSC patients (p = 0.002). Median pre- and post-treatment CA-125 levels for LGSC patients were 295.5 U/mL and 144 U/mL (52% decrease) (p < 0.001). The median pre- and post-treatment CA-125 levels for HGSC patients were 767.5 and 35.6 (96% decrease) (p < 0.001). For LGSC patients, 4/36 (11%) had partial response (PR), 30/36 (83%) had stable disease (SD), and 2/36 (6%) had progressive disease (PD). In HGSC patients, 27/36 (75%) had PR, and 9/36 (25%) SD. Median PFS for LGSC patients was 18.5 months and median OS was 47.4 months. CONCLUSIONS: This study provides further evidence of relative chemoresistance of LGSC in patients treated with NACT.

Comparison of patient reported symptom burden on an enhanced recovery after surgery (ERAS) care pathway in patients with ovarian cancer undergoing primary vs. interval tumor reductive surgery.

OBJECTIVE: To compare symptom burden and functional recovery in women undergoing primary cytoreductive surgery (PCS) or neoadjuvant chemotherapy (NACT) and interval cytoreductive surgery (ICS) within an enhanced recovery after surgery program (ERAS). METHODS: Symptom burden was measured using the MD Anderson Symptom Inventory-Ovarian Cancer, a 27-item validated tool that was administered preoperatively, daily while hospitalized, and weekly for 8 weeks after hospital discharge. Mixed-effect modeling was performed. RESULTS: 196 patients (71 PCS, 125 ICS) participated. Patients in the PCS group were younger, median age of 59 vs. 63 in ICS group. Median length of stay was 4 days for PCS and 3 days for ICS group. PCS pts had a significantly higher median surgical complexity score (4 vs. 2, p = 0.002), and longer median surgical time (257 min vs. 220 min, p = 0.03). While patients undergoing PCS had significantly different symptom burden profiles prior to surgery compared to those undergoing ICS, there were no significant differences in symptoms in the immediate in-hospital and extended post-hospital discharge period. Irrespective of the timing of surgery in relation to chemotherapy, patients undergoing intermediate or high complexity surgery had more nausea, fatigue, and higher total interference scores compared to patients undergoing low complexity surgery. CONCLUSION: Within a center with a standardized, systematic method for patient selection for PCS and a standardized ERAS care pathway, there were not significant differences in surgery-related symptoms related to recovery between patients undergoing PCS or ICS. However, patient-reported symptom burden and symptom interference did meaningfully differentiate based on surgical complexity score.

Prospective pilot trial with combination of propranolol with chemotherapy in patients with epithelial ovarian cancer and evaluation on circulating immune cell gene expression.

OBJECTIVE: To determine the feasibility of pharmacologic beta-adrenergic blockade in women with newly diagnosed stage II-IV epithelial ovarian cancer (EOC) throughout primary treatment. METHODS: Patients initiated propranolol prior to beginning chemotherapy or surgery. Feasibility was assessed as proportion able to complete 6 chemotherapy cycles while on adrenergic suppression. Descriptive statistics summarized surveys, and paired changes were analyzed using signed rank tests. Random-intercept Tobit models examined immune response. RESULTS: Median age was 59.9; 88.5% were stage IIIC/IV; and 38.5% underwent primary debulking. Thirty-two patients were enrolled; 3 excluded because they never took propranolol; an additional 3 didn't meet inclusion criteria, leaving 26 evaluable. Eighteen of 26 (69%), 90% credible interval (CI) of 53-81%, completed 6 chemotherapy cycles plus propranolol (an 82% posterior probability that the true proportion of success is ≥60%). Among the 23 patients with baseline and six month follow up data, overall QOL, anxiety, and depression improved (P < 0.05) and leukocyte expression of pro-inflammatory genes declined (P = 0.03) after completion of therapy. Decrease from baseline of serum IL-6 and IL-8 preceded response to chemotherapy (P < 0.0014). Change from baseline IL-10 preceded complete response. CONCLUSION: Use of propranolol during primary treatment of EOC is feasible and treatment resulted in decrease in markers of adrenergic stress response. In combination with chemotherapy, propranolol potentially results in improved QOL over baseline.

Electron cryotomography reveals ultrastructure alterations in platelets from patients with ovarian cancer.

Thrombocytosis and platelet hyperreactivity are known to be associated with malignancy; however, there have been no ultrastructure studies of platelets from patients with ovarian cancer. Here, we used electron cryotomography (cryo-ET) to examine frozen-hydrated platelets from patients with invasive ovarian cancer (n = 12) and control subjects either with benign adnexal mass (n = 5) or free from disease (n = 6). Qualitative inspections of the tomograms indicate significant morphological differences between the cancer and control platelets, including disruption of the microtubule marginal band. Quantitative analysis of subcellular features in 120 platelet electron tomograms from these two groups showed statistically significant differences in mitochondria, as well as microtubules. These structural variations in the platelets from the patients with cancer may be correlated with the altered platelet functions associated with malignancy. Cryo-ET of platelets shows potential as a noninvasive biomarker technology for ovarian cancer and other platelet-related diseases.

The DISINFECT Initiative: Decreasing the Incidence of Surgical INFECTions in Gynecologic Oncology.

BACKGROUND: Surgical site infections (SSIs) lead to increased patient morbidity and healthcare costs. Our objective was to decrease the SSI rate following gynecologic surgery. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

A call for new standard of care in perioperative gynecologic oncology practice: Impact of enhanced recovery after surgery (ERAS) programs.

Enhanced recovery after surgery (ERAS) programs aim to hasten functional recovery and improve postoperative outcomes. However, there is a paucity of data on ERAS programs in gynecologic surgery. We reviewed the published literature on ERAS programs in colorectal surgery, general gynecologic surgery, and gynecologic oncology surgery to evaluate the impact of such programs on outcomes, and to identify key elements in establishing a successful ERAS program. ERAS programs are associated with shorter length of hospital stay, a reduction in overall health care costs, and improvements in patient satisfaction. We suggest an ERAS program for gynecologic oncology practice involving preoperative, intraoperative, and postoperative strategies including; preadmission counseling, avoidance of preoperative bowel preparation, use of opioid-sparing multimodal perioperative analgesia (including loco-regional analgesia), intraoperative goal-directed fluid therapy (GDT), and use of minimally invasive surgical techniques with avoidance of routine use of nasogastric tube, drains and/or catheters. Postoperatively, it is important to encourage early feeding, early mobilization, timely removal of tubes and drains, if present, and function oriented multimodal analgesia regimens. Successful implementation of an ERAS program requires a multidisciplinary team effort and active participation of the patient in their goal-oriented functional recovery program. However, future outcome studies should evaluate the efficacy of an intervention within the pathway, include objective measures of symptom burden and control, study measures of functional recovery, and quantify outcomes of the program in relation to the rates of adherence to the key elements of care in gynecologic oncology such as oncologic outcomes and return to intended oncologic therapy (RIOT).

Role of cervical cytology in surveillance after radical trachelectomy for cervical cancer.

OBJECTIVE: There are currently no standard guidelines on the use of Papanicolaou (Pap) tests for surveillance after radical trachelectomy for cervical cancer. The goal of this study was to determine the usefulness of Pap tests in routine surveillance after radical trachelectomy for cervical cancer. METHODS: Cervical cancer patients who underwent radical trachelectomy from January 2004 through October 2015 and subsequently had at least one Pap test were retrospectively identified. Demographic and clinical characteristics were described and compared between patients with and without at least one abnormal Pap test. The Kaplan-Meier method was used to estimate time to first abnormal Pap test. RESULTS: Forty-one patients met inclusion criteria. Of these, 30 (73%) had at least one year in which more than one Pap test per year was obtained. Twenty-four (59%) had at least one abnormal Pap test. Of 238 total Pap tests collected, 44 (18%) were abnormal. The most common abnormality was ASCUS (52%, n=23). Other findings included LSIL (20%, n=9), HSIL (2%, n=1), and AGUS (25%, n=11). Median time from radical trachelectomy to first abnormal Pap test was 17.2months (range, 11.8-86.3). No patient had disease recurrence. Surgery type (laparoscopic, open, or robotic), trachelectomy specimen size, histology, device for stenosis prevention (pediatric Foley catheter or Smit Sleeve), and cerclage placement were not significant predictors of an abnormal Pap test. CONCLUSIONS: The rate of abnormal Pap tests after radical trachelectomy is high; however, the clinical significance of such abnormalities appears limited. The routine use of cervical cytology as surveillance after radical trachelectomy does not appear to substantially impact management decisions.

Characteristics of 10-year survivors of high-grade serous ovarian carcinoma.

OBJECTIVE: High-grade serous carcinoma (HGSC) generally presents at an advanced stage with poor long-term (LT) survival. Here we describe clinical features found in women surviving HGSC for ten or more years. METHODS: A multi-center research consortium was established between five participating academic centers. Patient selection criteria included high-grade serous ovarian, fallopian tube, or peritoneal carcinoma with at least ten years of follow up. Non-serous, borderline tumors and low-grade serous subtypes were excluded. RESULTS: The 203 identified LT ten-year survivors with HGSC were diagnosed at a median age of 57years (range 37-84years). The majority of patients had stage IIIC (72.4%) disease at presentation. Of those who underwent primary cytoreductive surgery, optimal cytoreduction was achieved in 143 (85.6%) patients. After a median follow up of 144months, 88 (46.8%) patients did not develop recurrent disease after initial treatment. Unexpected findings from this survey of LT survivors includes 14% of patients having had suboptimal cytoreduction, 11% of patients having an initial platinum free interval of <12months, and nearly 53% of patients having recurrent disease, yet still surviving more than ten years after diagnosis. CONCLUSIONS: LT survivors of HGSC of the ovary generally have favorable clinical features including optimal surgical cytoreduction and primary platinum sensitive disease. The majority of patients will develop recurrent disease, however many remained disease free for more than 10years. Future work will compare the clinical features of this unusual cohort of LT survivors with the characteristics of HGSC patients having less favorable outcomes.

Carcinoma of the Bartholin Gland: A Review of 33 Cases.

OBJECTIVE: Primary carcinoma of the Bartholin gland is a rare malignancy that accounts for approximately 5% of vulvar carcinomas. The aim of the study was to compare the outcomes of women with primary Bartholin gland carcinoma (BGC) with those with non-Bartholin gland-related vulvar carcinoma. MATERIALS AND METHODS: A retrospective chart review of 429 patients with invasive vulvar carcinoma evaluated at a single institution between 1993 and 2011 was performed. Medical records were reviewed for demographic data, pathologic information, treatment type, and recurrence/outcome information. These variables were compared between patients with primary BGC and patients with non-Bartholin gland-related vulvar carcinoma. RESULTS: Thirty-three (7.7%) of the 429 patients with invasive vulvar carcinoma had primary carcinoma of the Bartholin gland. Twenty-nine patients (87.9%) had squamous cell histology and 4 patients (12.1%) had adenocarcinoma. When compared with non-Bartholin gland-related vulvar carcinoma, patients with primary BGC had a younger age at diagnosis (median, 57 vs 63 years; P = 0.045), had a higher rate of stage III/IV disease (60.6% vs 35.8%; P = 0.008), and were more likely to receive radiation therapy (78.8% vs 43.9%; P < 0.001). However, there were no significant differences between the 2 groups with regard to histologic subtype, lymphovascular space involvement, perineural invasion, positive margins, recurrence-free survival, or overall survival. CONCLUSIONS: Despite being diagnosed at a more advanced stage, patients with primary carcinoma of the Bartholin gland seem to have similar oncologic outcomes and survival rates to patients with non-Bartholin gland-related vulvar carcinoma.

Platelets are not hyperreactive in patients with ovarian cancer.

Paraneoplastic thrombocytosis has been reported in different types of solid tumors, including ovarian epithelial cancer, and found to be associated with a worse outcome. Although the effect of cancer on increasing platelet counts is well documented, the effect of cancer on platelet functions is not well known. We compared in vitro aggregation response of platelets isolated from 34 patients with ovarian cancer to those of platelets from 19 patients with benign ovarian tumors. Aggregation studies were conducted in a light transmission aggregometer, using both a high and a low dose of ADP and collagen. We evaluated platelet preactivation by measuring the plasma concentration of ß-thromboglobulin (ß-TG) and platelet factor-4 (PF-4) as markers of platelet α granule secretion, using ELISA. We found that ovarian cancer is not associated with an enhanced aggregation response of platelets to ADP or collagen, and plasma concentration of ß-TG and PF-4 is not higher in patients with ovarian cancer compared to those in patients with benign ovarian tumors.

Clinical impact of selective and nonselective beta-blockers on survival in patients with ovarian cancer.

BACKGROUND: Preclinical evidence has suggested that sustained adrenergic activation can promote ovarian cancer growth and metastasis. The authors examined the impact of beta-adrenergic blockade on the clinical outcome of women with epithelial ovarian, primary peritoneal, or fallopian tube cancers (collectively, epithelial ovarian cancer [EOC]). METHODS: A multicenter review of 1425 women with histopathologically confirmed EOC was performed. Comparisons were made between patients with documented beta-blocker use during chemotherapy and those without beta-blocker use. RESULTS: The median age of patients in the current study was 63 years (range, 21-93 years). The sample included 269 patients who received beta-blockers. Of those, 193 (71.7%) were receiving beta-1-adrenergic receptor selective agents, and the remaining patients were receiving nonselective beta antagonists. The primary indication for beta-blocker use was hypertension but also included arrhythmia and postmyocardial infarction management. For patients receiving any beta-blocker, the median overall survival (OS) was 47.8 months versus 42 months for nonusers (P =.04). The median OS based on beta-blocker receptor selectivity was 94.9 months for those receiving nonselective beta-blockers versus 38 months for those receiving beta-1-adrenergic receptor selective agents (P<.001). Hypertension was associated with decreased OS compared with no hypertension across all groups. However, even among patients with hypertension, a longer median OS was observed among users of a nonselective beta-blocker compared with nonusers (38.2 months vs 90 months; P<.001). CONCLUSIONS: Use of nonselective beta-blockers in patients with EOC was associated with longer OS. These findings may have implications for new therapeutic approaches. Cancer 2015;121:3435-43. © 2015 American Cancer Society.

Paraneoplastic thrombocytosis in ovarian cancer.

BACKGROUND: The mechanisms of paraneoplastic thrombocytosis in ovarian cancer and the role that platelets play in abetting cancer growth are unclear. METHODS: We analyzed clinical data on 619 patients with epithelial ovarian cancer to test associations between platelet counts and disease outcome. Human samples and mouse models of epithelial ovarian cancer were used to explore the underlying mechanisms of paraneoplastic thrombocytosis. The effects of platelets on tumor growth and angiogenesis were ascertained. RESULTS: Thrombocytosis was significantly associated with advanced disease and shortened survival. Plasma levels of thrombopoietin and interleukin-6 were significantly elevated in patients who had thrombocytosis as compared with those who did not. In mouse models, increased hepatic thrombopoietin synthesis in response to tumor-derived interleukin-6 was an underlying mechanism of paraneoplastic thrombocytosis. Tumor-derived interleukin-6 and hepatic thrombopoietin were also linked to thrombocytosis in patients. Silencing thrombopoietin and interleukin-6 abrogated thrombocytosis in tumor-bearing mice. Anti-interleukin-6 antibody treatment significantly reduced platelet counts in tumor-bearing mice and in patients with epithelial ovarian cancer. In addition, neutralizing interleukin-6 significantly enhanced the therapeutic efficacy of paclitaxel in mouse models of epithelial ovarian cancer. The use of an antiplatelet antibody to halve platelet counts in tumor-bearing mice significantly reduced tumor growth and angiogenesis. CONCLUSIONS: These findings support the existence of a paracrine circuit wherein increased production of thrombopoietic cytokines in tumor and host tissue leads to paraneoplastic thrombocytosis, which fuels tumor growth. We speculate that countering paraneoplastic thrombocytosis either directly or indirectly by targeting these cytokines may have therapeutic potential. (Funded by the National Cancer Institute and others.).

Predictors of optimal cytoreduction in patients with newly diagnosed advanced-stage epithelial ovarian cancer: Time to incorporate laparoscopic assessment into the standard of care.

The standard management of advanced-stage ovarian cancer has been a subject of debate, and much controversy remains as to whether patients should have primary cytoreductive surgery followed by chemotherapy or neoadjuvant chemotherapy followed by interval cytoreductive surgery. In addition, there is increasing evidence that the patients who ultimately gain the most benefit from surgery are those with no residual disease at the completion of surgery (R0 resection). Therefore, to determine the best therapeutic strategy (primary cytoreductive surgery vs. neoadjuvant chemotherapy) for an individual patient, it is critically important to estimate the likelihood that primary cytoreductive surgery will leave no macroscopic residual disease. A number of studies have evaluated the use of serologic markers, such as CA-125, and imaging modalities, such as computed tomography (CT) or positron emission tomography/CT (PET/CT), to determine which patients are ideal candidates for primary cytoreductive surgery. More recently, laparoscopy has been proposed as a reliable predictor of R0 resection. In this report, we provide a review of the existing literature on the proposed criteria to predict the outcome of cytoreductive surgery and the role of laparoscopy-based scores in the management of advanced ovarian cancer.

Perioperative trajectory of patient reported symptoms: a pilot study in gynecologic oncology patients.

OBJECTIVE: With the growing focus on patient-centered care, patient reported outcomes (PROs) are becoming an important component to clinical trials and quality metrics. The objective of this study was to pilot the collection of patient reported symptom burden in women undergoing surgery in a gynecologic oncology practice. METHODS: Perioperative patient reported symptom burden was measured for women undergoing laparotomy on the gynecologic oncology service at the University of Texas MD Anderson Cancer Center. Symptoms were assessed using the M.D. Anderson Symptom Inventory (MDASI-OC), a 27 item tool validated for use in patients with ovarian cancer. The MDASI-OC was administered as a preoperative baseline, daily while admitted to the hospital after surgery, twice a week on the first week after discharge and then weekly until 8 weeks postoperatively. RESULTS: 29 patients were evaluable. Seventy-five percent of patients had a diagnosis of ovarian cancer. Of those patients, half underwent a primary debulking surgery and the other half had neoadjuvant chemotherapy prior to interval cytoreductive surgery. In the postoperative inpatient setting, the five symptoms with the highest overall burden were fatigue, pain, abdominal pain, dry mouth and drowsiness. Longitudinal change of the top 5 symptoms during hospitalization did not show any significant difference between those who had neoadjuvant chemotherapy and those who did not. CONCLUSION: The collection of longitudinal PROs to assess symptom burden is feasible in patients undergoing gynecologic oncology surgery. Patient reported outcomes are a crucial component of patient-centered research and the longitudinal collection and analysis of symptom burden can allow for more meaningful comparisons of surgical technique and perioperative care.

Significance of lymph node ratio in defining risk category in node-positive early stage cervical cancer.

OBJECTIVE: The ratio of positive to negative lymph nodes, or lymph node ratio (LNR), is an important prognostic factor in several solid tumors. The objective of this study was to determine if LNR can be used to define a high-risk category of patients with node-positive early stage cervical cancer. METHODS: We performed a retrospective review of patients diagnosed with node-positive stage I or II cervical cancer who underwent radical hysterectomy and pelvic +/- para-aortic lymphadenectomy at MD Anderson from January 1990 to December 2011. Univariate and multivariate analyses were used to identify prognostic factors for progression-free (PFS) and overall survival (OS). RESULTS: Ninety-five patients met the inclusion criteria and were included in the analysis. Median total nodes removed were 19 (range 1-58), and median number of positive nodes was 1 (range 1-12). Fifty-eight patients (61%) received radiation with concurrent cisplatin and 27 patients (28%) received radiotherapy alone. Twenty-one (22%) patients recurred. On multivariate analysis, a LNR > 6.6% was associated with a worse PFS (HR = 2.97, 95% CI 1.26-7.02, p = 0.01), and a LNR > 7.6% with a worse OS (HR = 3.96, 95% CI 1.31-11.98, p = 0.01). On multivariate analysis, positive margins were associated with worse PFS (p = 0.001) and OS (p = 0.002), and adjuvant radiotherapy (p = 0.01) with improved OS. CONCLUSIONS: LNR appears to be a useful tool to identify patients with worse prognosis in node-positive early stage cervical cancer. LNR may be used in addition to pathologic risk factors to tailor adjuvant treatment in this population.

Improvement in quality of life after robotic surgery results in patient satisfaction.

BACKGROUND: There are well-described benefits to minimally invasive surgery including decreased blood loss, shorter hospital-stay, and faster recovery. The role of robotic surgery in gynecologic oncology has become increasingly prominent; however limited data are available on quality of life (QOL) after robotic surgery. METHODS: In this prospective, IRB-approved study, women scheduled for robotic surgery for a gynecologic indication between May 2008 and February 2012 completed validated QOL measures at baseline, 6 weeks (6wk), and 4 months postoperative (4mo). Functional status (SF-12), symptom severity and interference (MDASI), sexual function (FSFI), and satisfaction with decision (SWD) were assessed at relevant time points. Differences between groups were evaluated using the Mann-Whitney test. RESULTS: Among 408 women who underwent robotic surgery 278 (68%) completed the QOL measures. Median age was 55.6 years (range 25.7-85.1). Median BMI was 31.3kg/m(2). The majority of patients were white (75%). The most common indication for surgery was endometrial cancer/hyperplasia (59.7%). While physical functioning declined from baseline to 6wk (51.4 to 41.6, p<0.001), it improved by 4mo (53.5). Mental functioning improved over time (baseline 48.6, 6wk 52.8, and 4mo 55.6, p<0.001). Symptom severity decreased over time (p<0.001) as did symptom interference (p<0.001). Sexual function improved significantly from baseline (8.6) to 4mo (20.2, p<0.001). Patients were satisfied with their decision making (SWD=30). CONCLUSION: In this prospective study, general health, symptom burden and sexual function returned to or improved beyond baseline levels within 6 weeks of surgery. Overall, women were satisfied with their decision to undergo robotic surgery.

Impact of Lymph Node Ratio and Adjuvant Therapy in Node-Positive Endometrioid Endometrial Cancer.

OBJECTIVES: To determine if the ratio of positive to negative lymph nodes, or lymph node ratio (LNR), is a prognostic variable in patients with node-positive endometrial cancer and the impact of adjuvant therapy on survival. METHODS: After institutional review board approval, a retrospective review of patients diagnosed as having stage IIIC endometrioid or mixed endometrioid endometrial cancer at a single institution from January 2000 through October 2011 was performed. Clinicopathologic and adjuvant treatment data were collected. Univariate and multivariate analysis were used to identify prognostic factors for progression-free (PFS) and overall survival. RESULTS: One hundred twenty-four patients with stage IIIC1 (n = 64) and IIIC2 (n = 60) endometrial cancer were included in the analysis. Median age was 60 years (range, 25-84 years), and median follow-up was 49.4 months (range, 0.1-301.6 months). Age >70 years was identified as a prognostic factor for worse PFS (P = 0.0002) and overall survival (P = 0.0002) on multivariate analysis. Patients in this cohort receiving any adjuvant radiotherapy showed improved PFS (hazard ratio [HR], 0.34; 95% CI, 0.13-0.90; P = 0.03) compared with those receiving any adjuvant chemotherapy (HR, 2.33; 95% CI, 1.16-4.65; P = 0.02). In a subgroup analysis, patients with at least 10 nodes removed (n = 81) with an LNR greater than 50% had a PFS of 25.2 months compared with 135.6 months with an LNR of 50% or less (HR, 3.87; 95% CI, 1.15-13.04; P = 0.03). CONCLUSIONS: Lymph node ratio may define a subgroup of stage IIIC endometrial cancers at increased risk for recurrence. Adjuvant radiotherapy was associated with decreased recurrence risk.

Minimally invasive surgery for endometrial cancer: does operative start time impact surgical and oncologic outcomes?

OBJECTIVE: Recent literature in ovarian cancer suggests differences in surgical outcomes depending on operative start time. We sought to examine the effects of operative start time on surgical outcomes for patients undergoing minimally invasive surgery for endometrial cancer. METHODS: A retrospective review was conducted of patients undergoing minimally invasive surgery for endometrial cancer at a single institution between 2000 and 2011. Surgical and oncologic outcomes were compared between patients with an operative start time before noon and those with a surgical start time after noon. RESULTS: A total of 380 patients were included in the study (245 with start times before noon and 135 with start times after noon). There was no difference in age (p=0.57), number of prior surgeries (p=0.28), medical comorbidities (p=0.19), or surgical complexity of the case (p=0.43). Patients with surgery starting before noon had lower median BMI than those beginning after noon, 31.2 vs. 35.3 respectively (p=0.01). No significant differences were observed for intraoperative complications (4.4% of patients after noon vs. 3.7% of patients before noon, p=0.79), estimated blood loss (median 100 cc vs. 100 cc, p=0.75), blood transfusion rates (7.4% vs. 8.2%, p=0.85), and conversion to laparotomy (12.6% vs. 7.4%, p=0.10). There was no difference in operative times between the two groups (198 min vs. 216.5 min, p=0.10). There was no association between operative start time and postoperative non-infectious complications (11.9% vs. 11.0%, p=0.87), or postoperative infections (17.8% vs. 12.3%, p=0.78). Length of hospital stay was longer for surgeries starting after noon (median 2 days vs. 1 day, p=0.005). No differences were observed in rates of cancer recurrence (12.6% vs. 8.8%, p=0.39), recurrence-free survival (p=0.97), or overall survival (p=0.94). CONCLUSION: Our results indicate equivalent surgical outcomes and no increased risk of postoperative complications regardless of operative start time in minimally invasive endometrial cancer staging, despite longer length of hospital stay for surgeries beginning after noon.