Evaluation of Surgical Approaches and Use of Adjuvant Radiotherapy with Respect to Oncologic Outcomes in the Management of Clinically Early-Stage Cervical Carcinoma.

The standard of care for early-stage cervix cancer is radical hysterectomy with pelvic lymphadenectomy. Adjuvant radiotherapy (RT) or chemoradiotherapy may be administered to reduce the risk of recurrence in patients considered to be at elevated risk based on a combination of pathologic factors. We performed a retrospective review to determine oncologic outcomes in patients treated for early-stage cervix cancer and to determine if surgical approach impacted oncologic outcomes or the decision to use adjuvant therapy. In total, 174 women underwent radical hysterectomy and pelvic lymphadenectomy over the 15-year period. Most of these women (146) had open surgery and 28 had minimally invasive surgery (MIS). In total, 81 had adjuvant pelvic RT; 76 in the open surgery group (52%) and 5 in the MIS group (18%). Five-year PFS and OS, respectively, were 84% and 91%. Five-year PFS was significantly lower in patients who had MIS vs. open surgery, without a difference in 5-year OS, suggesting MIS should be avoided. Five-year PFS was the same with RT or with its omission, despite those treated with RT having higher risk disease. We have demonstrated excellent outcomes in patients with early-stage cervix cancer after primary surgery and selective use of RT, with few recurrences and excellent survival.

Role of primary care enrolment in advanced cervical cancer diagnosis: a population-based case-control study.

INTRODUCTION: The elimination of cervical cancer will only be achievable through primary and secondary prevention. The aim of this study was to determine the effect of primary care enrolment on the prevention of advanced cervical cancer. METHODS: Using a population-based case-control study, all women (n=5548) above 18 years of age who were diagnosed with cervical cancer between January 2006 and December 2015 in Ontario, Canada were selected for the analysis. The controls were women (n=27 740) above 18 years of age and without a diagnosis of cervical cancer. Five controls were matched to each case by year of birth. Descriptive statistics were used to compare the patients and controls. Multiple imputations and logistic regression were used to estimate the correlation between enrolment with a primary care provider and diagnosis of cervical cancer. RESULTS: A total of 44% of advanced cervical cancer patients and 56% of controls had a screening test 10 years before the index date. The odds of having had a Pap test in the 3 and 10 years before were higher when patients were enrolled with a primary care provider (OR 3.5 and 5.1, p<0.001). The correlation between screening and advanced cervical cancer (stage II-IV) incidence was modified by primary care enrolment: if the patient was enrolled with a primary care provider and had at least one screen in the previous 10 years, the OR of developing advanced cervical cancer was 0.42 (95% CI 0.40 to 0.43); if the patient was not enrolled the OR was 0.78 (95% CI 0.72 to 0.84). DISCUSSION: Primary care enrolment is an effect modifier of cervical cancer screening on advanced cervical cancer incidence. Efforts should be made to increase the capacity of primary care providers to offer screening in order to eradicate cervical cancer.

Comparative study of grade 3/4 toxicity associated with intraperitoneal chemotherapy administered after primary versus interval surgical debulking in ovarian cancer.

OBJECTIVE: To determine the prevalence of grade 3 or 4 toxicity associated with intraperitoneal (IP) chemotherapy subsequent to primary surgical debulking compared to post-neoadjuvant chemotherapy and interval debulking in advanced ovarian cancer. METHODS: Patients receiving IP chemotherapy from 2006 to 2010 were reviewed. Study cohort was stratified by initial treatment (upfront surgery vs neoadjuvant chemotherapy). The National Cancer Institute toxicity grading scale was used to assess treatment-related toxicities immediately before each cycle. The χ² test was used to check for association between categorical variables. RESULTS: Thirty-three patients received IP chemotherapy after optimal debulking. Sixteen patients had upfront surgery. The total number of IP chemotherapy cycles administered was 134. Significantly, more patients treated with IP chemotherapy after intravenous neoadjuvant chemotherapy experienced fatigue (P=0.038) compared to those treated after upfront surgery. During the course of IP regimen, the patients having upfront surgery tended to experience more grade 3/4 hematologic toxicities (P=0.06) and abdominal pain (P=0.08). Twenty-four (73%) of 33 patients completed all prescribed IP chemotherapy cycles. There was no significant difference between the 2 groups in need for dose reduction or delays, use of paclitaxel on day 8, neurologic/gastrointestinal/metabolic toxicities, and IP port complications. CONCLUSIONS: Intraperitoneal chemotherapy can be given after optimal primary surgery or interval surgery after neoadjuvant chemotherapy with similar toxicity profile. Toxicity data can be used to plan for optimal IP chemotherapy delivery, patient counseling, and ongoing supportive care.

Application of 3-d angiography in the management of placenta percreta treated with repeat uterine artery embolization.

BACKGROUND: Rising Caesarean section rates have increased rates of abnormally invasive placentation. In the management of such invasive placentation, hysterectomy may result in greater morbidity than more conservative measures. Non-surgical interventions such as uterine artery embolization (UAE) attempt to decrease placental perfusion and augment placental resorption. Repeat UAE may decrease the risk of unpredictable hemorrhage requiring emergency intervention. Three-dimensional angiography is a novel technology for assessing volume with objective measures of internal flow. CASE: We report a case of placenta previa percreta that was treated conservatively by repeat UAE for persistent densely perfused placenta. Three-dimensional angiography was used to objectively assess placental characterization and vascularization. CONCLUSION: Repeat UAE may be beneficial in reducing the risk of delayed hemorrhage in women with placenta previa accreta or percreta managed conservatively. Objective assessment of placental volume and vascularity by 3-D angiography can provide data on patients at risk and allow case selection for repeat UAE.

Assessment of outcomes in surgically staged I/II endometrial adenocarcinoma patients treated with postoperative vaginal vault radiotherapy only.

OBJECTIVE: To examine the efficacy of vaginal vault radiotherapy as adjuvant treatment for patients with high-grade, stage I/II endometrial adenocarcinoma who have been surgically staged. METHODS: A retrospective chart review of 77 women between 1995 and 2006 with high-grade surgically staged I and II endometrial adenocarcinoma, who were treated with postoperative vaginal vault radiotherapy alone, was performed. The primary study end points were recurrence risk and sites of recurrence. The secondary end points were disease-free and overall survival. Kaplan-Meier estimates were calculated for overall and disease-free survival. RESULTS: Seventy-seven women were identified and met inclusion criteria. Sixty-seven (87%) had grade 3 histologic features on final pathologic report. Forty-two patients (55%) were classified as stage IB, having superficial myometrial invasion; 21 (27%) were stage IC, with deep invasion; and 6 (8%) were stage II, involving the cervix. The median follow-up was 80 months (6.6 years). There were 10 recurrences (13.0%), of which 3 were local: 1 involving the vaginal apex; 1, the lower vagina and pelvic sidewall; and 1, the lower vagina. The 5-year recurrence risk was 11.2% and the 5-year survival probability 88.9%. CONCLUSIONS: It seems that for this cohort of 77 patients with surgically staged I and II grade 3 endometrial adenocarcinoma, adjuvant vaginal vault radiotherapy alone leads to acceptable recurrence rates and survival while minimizing morbidity.

Urine metabolite analysis offers potential early diagnosis of ovarian and breast cancers.

PURPOSE: Metabolomics is a new, rapidly expanding field dedicated to the global study of metabolites in biological systems. In this article metabolomics is applied to find urinary biomarkers for breast and ovarian cancer. EXPERIMENTAL DESIGN: Urine samples were collected from early- and late-stage breast and ovarian cancer patients during presurgical examinations and randomly from females with no known cancer. After quantitatively measuring a set of metabolites using nuclear magnetic resonance spectroscopy, both univariate and multivariate statistical analyses were employed to determine significant differences. RESULTS: Metabolic phenotypes of breast and ovarian cancers in comparison with normal urine and with each other revealed significance at Bonferroni-corrected significance levels resulting in unique metabolite patterns for breast and ovarian cancer. Intermediates of the tricarboxylic acid cycle and metabolites relating to energy metabolism, amino acids, and gut microbial metabolism were perturbed. CONCLUSIONS: The results presented here illustrate that urinary metabolomics may be useful for detecting early-stage breast and ovarian cancer.

A population-based study of the determinants of physical activity in ovarian cancer survivors.

BACKGROUND: Regular physical activity is associated with quality of life and other health-related outcomes in ovarian cancer survivors, but participation rates are low. This study investigated the determinants of physical activity in ovarian cancer survivors. METHODS: A population-based, cross-sectional, mailed survey of ovarian cancer survivors in Alberta, Canada, was performed. Measures included self-reported physical activity, medical and demographic factors, and social cognitive variables from the Theory of Planned Behavior. RESULTS: A total of 359 women participated (51.4% response rate), of whom 112 (31.1%) were meeting physical activity guidelines. Variables associated with meeting guidelines were younger age, higher education and income, being employed, lower body mass index, absence of arthritis, longer time since diagnosis, earlier disease stage, and being disease-free. Analysis of the Theory of Planned Behavior variables indicated that 36% of the variance in physical activity guidelines was explained, with intention being the sole independent correlate (?=.56; P < .001). CONCLUSION: Various demographic and medical factors can help identify ovarian cancer survivors at risk for physical inactivity. Interventions should attempt to increase physical activity intentions in this population by focusing on instrumental and affective attitudes as well as perceptions of control.

The significance of duration of chemotherapy interruptions due to interval surgery in ovarian cancer patients treated with neoadjuvant chemotherapy.

OBJECTIVE: To examine the prognostic significance of interruptions to chemotherapy arising from delayed primary surgical debulking following neoadjuvant chemotherapy in women undergoing treatment for ovarian cancer. METHODS: We carried out a retrospective chart review to identify women with ovarian cancer who were treated with neoadjuvant chemotherapy and planned delayed primary surgical debulking. Cox regression modelling was used to identify significant predictors of progression-free and overall survival, using well-established prognostic variables and time delays between courses of chemotherapy perioperatively, stratified by residual disease status. RESULTS: Ninety-seven patients with complete data were identified. Their median age was 65.4 years. Fifty-four patients (56%) were left with optimal residual disease (< 1 cm), and 43 patients had suboptimal residual disease. The median delay from the last cycle of chemotherapy to the time of surgery was 29 days (range 20-72). The median delay from surgery to resumption of cytotoxic therapy was 23 days (range 8-65). Chemotherapy courses were interrupted for a median of 50 days (range 36-119) around the time of surgery. No effect was observed on progression-free interval by interruptions to chemotherapy, regardless of residual disease status. With respect to overall survival, the time to resumption of chemotherapy in days and the time delay in days between the two chemotherapy cycles peri-operatively were identified as statistically significant predictors only in patients with suboptimal residual disease. In patients with optimal residual disease status, neither the time of interruption between the two chemotherapy cycles peri-operatively nor the time to resumption of chemotherapy after surgical debulking was significantly predictive of overall survival. CONCLUSION: In women undergoing treatment for ovarian cancer, the interval between surgery and the resumption of chemotherapy in patients with suboptimal residual disease should be kept as short as possible.

Longitudinal assessments of quality of life in endometrial cancer patients: effect of surgical approach and adjuvant radiotherapy.

PURPOSE: Adjuvant radiotherapy (RT) is often considered for endometrial cancer. We studied the effect of RT and surgical treatment on patients' quality of life (QOL). METHODS AND MATERIALS: All patients referred to the gynecologic oncology clinics with biopsy findings showing endometrial cancer were recruited. QOL assessments were performed using the European Organization for Research and Treatment of Cancer QOL questionnaire-C30, version 3. Assessments were obtained at study entry and at regular 3-month intervals for a maximum of 2 years. Open-ended telephone interviews were done every 6 months. Linear mixed regression models were built using QOL domain scores as dependent variables, with the predictors of surgical treatment and adjuvant RT type. RESULTS: A total of 40 patients were recruited; 80% of the surgeries were performed by laparotomy. Significant improvements were seen in most QOL domains with increased time from treatment. Adjuvant RT resulted in significantly more severe bowel symptoms and improvement in insomnia compared with conservative follow-up. No significant adverse effect from adjuvant RT was seen on the overall QOL. Bowel symptoms were significantly increased in patients treated with laparotomy compared with laparoscopy in the patients treated with whole pelvic RT. Qualitatively, about one-half of the patients noted improvements in their overall QOL during follow-up, with easy fatigability the most prevalent. CONCLUSION: No significant adverse effect was seen on patients' overall QOL with adjuvant pelvic RT after the recovery period. The acute adverse effects on patients' QOL significantly improved with an increasing interval from diagnosis.

Physical activity in ovarian cancer survivors: associations with fatigue, sleep, and psychosocial functioning.

UNLABELLED: Physical activity has been associated with better health-related outcomes in several cancer survivor groups but very few data exist for women with ovarian cancer. The purpose of this study was to investigate the associations between physical activity and health-related outcomes in ovarian cancer survivors and to examine any dose-response relationship. PATIENTS AND METHODS: A cross-sectional postal survey of ovarian cancer survivors on and off treatment identified through the Alberta Cancer Registry was performed. Participants completed self-report measures of physical activity, cancer-related fatigue, peripheral neuropathy, depression, anxiety, and happiness, as well as demographic and medical variables. RESULTS: A total of 359 ovarian cancer survivors participated (51.4% response rate) of whom 31.1% were meeting the public health physical activity guidelines of the Centers for Disease Control and Prevention. Those meeting guidelines reported significantly lower fatigue than those not meeting guidelines (mean difference, 7.1; 95% confidence interval, 5.5-8.8; d = 0.87; P < 0.001). Meeting guidelines was also significantly inversely associated with peripheral neuropathy, depression, anxiety, sleep latency, use of sleep medication, and daytime dysfunction and was positively associated with happiness, sleep quality, and sleep efficiency. There was no evidence of a dose-response relationship beyond meeting or not meeting the guidelines for any variables. CONCLUSIONS: Ovarian cancer survivors who were meeting physical activity guidelines reported more favorable outcomes of fatigue, peripheral neuropathy, sleep, and psychosocial functioning.

Can surgical debulking reverse platinum resistance in patients with metastatic epithelial ovarian cancer?

OBJECTIVES: To examine the impact of delayed primary interval surgical debulking in women with ovarian cancer who show resistance to neoadjuvant platinum-based chemotherapy. METHODS: We carried out retrospective chart reviews to identify women treated for ovarian cancer between 1997 and 2005 who were resistant to neoadjuvant platinum-based chemotherapy based on CA-125 criteria. "Platinum resistance" was defined as having a decrease in serum CA-125 of less than 50% after three cycles of chemotherapy from the time of initial diagnosis. Associations between residual disease and platinum sensitivity status at time of first recurrence were identified using chi-square tests. Median progression-free interval was estimated using the Kaplan Meier method. RESULTS: Ninety-one women were treated with neoadjuvant chemotherapy. Seventeen patients met the criteria for platinum resistance after neoadjuvant chemotherapy. The mean decline in serum CA-125 levels was 18.2%. All patients underwent attempts at surgical debulking. Optimal debulking was achieved in 10 patients (59%). There was a significant association between decreasing amount of residual disease and improving clinical response after primary treatment (P=0.007), and with platinum sensitivity status at the time of first recurrence (P=0.023). The estimated median progression free survival was 10.7 months. CONCLUSION: In women with ovarian cancer who have demonstrated platinum resistance after primary neoadjuvant chemotherapy, optimal tumour debulking can further improve response to subsequent platinum-based chemotherapy and prognosis.

Physical activity preferences of ovarian cancer survivors.

OBJECTIVE: Regular physical activity is positively associated with quality of life in ovarian cancer survivors, but no data exist on how best to promote activity in this population. This study investigated the interests and preferences of ovarian cancer survivors with regard to physical activity participation. METHODS: A provincial, population-based postal survey of ovarian cancer survivors in Alberta, Canada, was performed including measures of self-reported physical activity, medical and demographic variables, and physical activity preferences. RESULTS: A total of 359 women participated (51.4% response rate). Over half expressed interest in participating in a physical activity program (53.8%), with a further 32.9% maybe interested. The most common preferences were for programs to be home-based (48.9%), start post-treatment (69.5%), and involve walking (62.7%). There were differences in preferences based on demographic, but not medical, factors. CONCLUSION: The majority of ovarian cancer survivors expressed interest in participating in physical activity programs; however, some preferences varied by demographic factors. Designing physical activity interventions according to these preferences may optimize adherence and outcomes in ovarian cancer survivors.

Variations in ultrasound reporting on patients referred for investigation of ovarian masses.

OBJECTIVE: Ultrasound characteristics play an important role in the evaluation and management of patients with an ovarian mass. We sought to quantify the variability in the reporting practices of radiologists in different practice environments. METHOD: We carried out a prospective audit of all patients referred to a tertiary care gynaecologic oncology clinic over a three-month period for management of an ovarian mass. Each patient's presenting symptoms, level of CA125 in serum, and previous ultrasound report were reviewed in detail, and both the environment where the ultrasound examination had been performed and the description of important predictive ultrasound characteristics for underlying risk of malignancy were noted. Descriptive statistics were used to summarize demographic variables. Cross-tabulations and chi-square tests were used to detect significant associations between categorical variables. RESULTS: In the three-month period, 42 patients were referred to our clinic. The most common presenting symptom was abdominal or pelvic pain (65% of patients). Ultrasound examinations had been conducted in private clinics, community hospitals, and teaching hospitals. Significant variations in the reporting were noted. The important ultrasound characteristic most often not reported (approximately 80% of reports) was Doppler flow assessment of the mass. Five reports (12%) did not include information that would be needed to make a recommendation resulting in repeat ultrasound examination. We found no significant variation in reporting practices between private clinics and community hospitals. CONCLUSION: Current reporting practices for ultrasound assessments in women with an ovarian mass vary considerably. They could be improved by use of a standardized synoptic reporting template.

Importance of CA125 normalization during neoadjuvant chemotherapy followed by planned delayed surgical debulking in patients with epithelial ovarian cancer.

OBJECTIVES: To examine the prognostic significance, in patients with ovarian cancer, of normalization of CA125 levels in serum during neoadjuvant chemotherapy treatment combined with delayed primary surgical debulking. METHODS: We carried out a retrospective chart review to identify ovarian cancer patients treated between 1997 and 2005 with neoadjuvant chemotherapy and delayed surgical debulking. Serum levels of CA125 were measured at baseline, prior to each cycle of chemotherapy, and before surgery. "CA125 normalization" was defined as a reduction in serum CA125 levels, in patients with elevated levels at diagnosis, to less than 35 kU/L. Cox proportional hazard models were built to model progression-free survival and overall survival. RESULTS: Ninety patients met the inclusion criteria. Sixteen patients (17.8%) had CA125 normalization before surgery, and 52 patients (57.8%) had normalization at the conclusion of all primary chemotherapy. Cox regression showed that CA125 normalization from neoadjuvant chemotherapy before surgery did not significantly predict survival. Patients who failed to normalize CA125 after finishing primary chemotherapy had shortened progression-free survival (HR 3.1; 95% CI 1.9-5.1, P < 0.001) and overall survival (HR 2.6; 95% CI 1.0-6.9, P < 0.05). The estimated median survival was 72 months (95% CI 64.6-79.40) in patients with normal CA125 at the end of chemotherapy, whereas in those with persistently elevated CA125 the corresponding estimated median survival was 46.8 months (95% CI 38.2-55.3). CONCLUSION: CA125 normalization after neoadjuvant chemotherapy is not an independent predictor of either progression-free or overall survival. Patients with persistently elevated CA125 after completing primary treatment had significantly inferior survivals compared with those who normalized CA125.

Suprapubic or urethral catheter: what is the optimal method of bladder drainage after radical hysterectomy?

BACKGROUND: Lower urinary tract dysfunction is a common morbidity related to radical hysterectomy (RAH). Although transurethral catheterization (TUC) has traditionally been used for postoperative bladder drainage following RAH, suprapubic catheterization (SPC) is an alternative method that may be advantageous. OBJECTIVES: To determine, by means of a retrospective cohort study, the incidence of urinary tract infection (UTI), duration of postoperative hospital stay, and time to trial of voiding in women catheterized suprapubically or transurethrally after RAH for early stage cervical cancer. METHODS: Two hundred twelve patients who underwent RAH and staging for stage IA1 + LVS, 1A2, and 1B1 cancer of the cervix in Edmonton between 1996 and 2006 were included in the study. Three gynaecologic oncologists performed the surgeries. Operative, postoperative, and demographic data were extracted from patient records. Patients were catheterized either suprapubically (SPC group) or transurethrally (TUC group) according to the surgeon's discretion. Comparative tests and multivariate regression analysis were used to compare outcome measures between the groups and to adjust for confounding variables. RESULTS: The TUC group had a higher proportion of patients with UTI (27%) than the SPC group (6%) (P < 0.001). The SPC group had a shorter postoperative hospital stay (4.8 vs. 5.7 days; P < 0.001) and an earlier trial of voiding (2.7 vs. 4.4 days; P < 0. 001). Following regression analysis, statistically significant differences remained for UTI and time to initiation of a trial of voiding. CONCLUSION: After RAH for early stage cervical cancer, suprapubic catheterization is associated with a lower rate of UTI and an earlier trial of voiding than transurethral catheterization.

Omental chemotherapy effects as a prognostic factor in ovarian cancer patients treated with neoadjuvant chemotherapy and delayed primary surgical debulking.

BACKGROUND: We sought to assess the prognostic significance of chemotherapy effect on upper abdominal metastatic disease. METHODS: Retrospective chart reviews were carried out from 1997 to 2005 to identify ovarian cancer patients treated with neoadjuvant chemotherapy. Pathologic examinations of resected omental and ovarian tumors for the presence of chemotherapy effect were performed. Cox proportional hazard models were built to model time to progression and death by using predictor variables of age, tumor grade, amount and location of largest residual disease, and the presence of chemotherapy effects on resected tumors. RESULTS: Sixty-six patients with available slides and clinical information were identified. The presence of omental chemotherapy effects was observed in 58 patients (88%). Identified independent statistically significant predictors for progression-free survival included presence of omental chemotherapy effect (hazard ratio [HR], .38; 95% confidence interval [95% CI], .17-.89; P = .026) and suboptimal tumor residuals in upper abdominal location compared with pelvic location (HR, 2.41; 95% CI, 1.06-5.48; P = .035). The presence of omental chemotherapy effect was the only statistically significant predictor of disease specific survival (HR, .21; 95% CI, .068-.639; P = .006). The estimated median survival for the group with positive omental chemotherapy effect was 84.45 months (95% CI, 69.63-99.28). The corresponding statistic in patients with no observed response to chemotherapy was 31.15 months (95% CI, 21.84-40.47). CONCLUSIONS: Upper abdominal disease location and its response to chemotherapy were independent prognostic factors for progression-free survival. Aggressive upper abdominal debulking procedures are recommended to improve oncologic outcomes.

The definition of optimal inguinal femoral nodal dissection in the management of vulva squamous cell carcinoma.

OBJECTIVES: To reject the hypothesis that the number of nodes removed at time of surgical staging for vulva cancer is not an important prognostic factor. METHODS: Retrospective chart reviews were carried out from 1980-2004 to identify patients with squamous cell vulva carcinoma treated with radical vulvectomy and bilateral inguinal femoral lymph node dissection. Patients' demographics, disease characteristics, the number of lymph nodes removed at surgery, and standard oncologic outcomes were recorded. Cox proportional hazard models were built to model times to clinical progression and death using predictor variables of: age, tumor size and maximum depth of invasion, resection margin status, and total number of nodes removed. RESULTS: Fifty-eight patients were identified. The median lesion size was 3.5 cm. The median depth of invasion was 7.5 mm. The 20th percentile for total number of lymph nodes removed was 10. Adjuvant radiation therapy was given in 31% of patients. At a median follow-up of 37 months, recurrence was observed in 17 patients (29.3%). Cox regressions showed the total number of nodes removed less than 10 to be the only significantly predictive of shorter time to first progression (HR = 12.88, 95% CI = 1.47-112.89, P = .021) and shorter disease specific survivals (HR = 11.41, 95% CI = 2.21-58.86, P = .004) (HR, hazard ratio; CI, confidence interval). CONCLUSION: The total number of nodes removed at time of surgical staging is an independent survival prognostic factor. A total of at least 10 nodes from a bilateral dissection can be used to define an optimal evaluation.