Up-Front Multigene Panel Testing for Cancer Susceptibility in Patients With Newly Diagnosed Endometrial Cancer: A Multicenter Prospective Study.

PURPOSE: Clinical utility of up-front multigene panel testing (MGPT) is directly related to the frequency of pathogenic variants (PVs) in the population screened and how genetic findings can be used to guide treatment decision making and cancer prevention efforts. The benefit of MGPT for many common malignancies remains to be determined. In this study, we evaluated up-front MGPT in unselected patients with endometrial cancer (EC) to determine the frequency of PVs in cancer susceptibility genes. METHODS: Patients with EC were prospectively enrolled at nine Ohio institutions from October 1, 2017, to December 31, 2020. Nine hundred and sixty-one patients with newly diagnosed EC underwent clinical germline MGPT for 47 cancer susceptibility genes. In addition to estimating the prevalence of germline PVs, the number of individuals identified with Lynch syndrome (LS) was compared between MGPT and tumor-based screening. RESULTS: Likely pathogenic variants or PVs were identified in 97 of 961 women (10.1%). LS was diagnosed in 29 of 961 patients (3%; 95% CI, 2.1 to 4.3), with PVs in PMS2 most frequent. MGPT revealed nine patients with LS in addition to the 20 identified through routine tumor-based screening. BRCA1 and BRCA2 PVs were found in 1% (10 of 961; 95% CI, 0.6 to 1.9) of patients and that group was significantly enriched for type II ECs. CONCLUSION: This prospective, multicenter study revealed potentially actionable germline variants in 10% of unselected women with newly diagnosed EC, supporting the use of up-front MGPT for all EC patients. The discovery that BRCA1 or BRCA2 heterozygotes frequently had type II cancers points to therapeutic opportunities for women with aggressive histologic EC subtypes.

Triple negative lobular breast carcinoma metastatic to an ovarian fibrothecoma.

A postmenopausal woman with lobular breast carcinoma metastatic to a large ovarian fibrothecoma is presented. The two metastatic tumor nodules were grossly subtle and could have been overlooked in the background of the large ovarian stromal tumor. Thorough sampling of the tumor for histologic examination and supporting immunohistochemical stains were important in establishing the diagnosis. Differential diagnostic considerations are discussed.

Training to maintain surgical skills during periods of robotic surgery inactivity.

BACKGROUND: The study was performed to establish a level of practice needed for newly-trained residents to maintain robotic surgical skills during periods of robotic inactivity. METHODS: Ten surgical residents were trained to a standardized level of robotic surgery proficiency with inanimate models. At the end of two, four and six weeks, the residents practiced with the models for a total of one hour. Each resident performed a timed tissue closure task immediately after reaching the proficiency standards and twice in succession at eight weeks. Time to completion was compared between the three trials with a repeated measures ANOVA and a post-hoc test. RESULTS: Average time to complete the tissue closure task decreased by more than 25% over the period between reaching the proficiency standards and the trials at eight weeks, with the difference significant (P < 0.004). CONCLUSIONS: Biweekly practice for one hour was sufficient to maintain robotic surgical skills.

Using virtual reality to maintain surgical skills during periods of robotic surgery inactivity.

Periodic practice is needed for newly trained robotic surgeons to maintain skills during periods of robotic inactivity. The current study was performed to determine whether virtual robotic skill maintenance can serve as an adequate substitute for practice on a surgical robot. Eleven surgical residents with no prior robotic training were trained to a level of robotic proficiency with inanimate models, including a needle driving pad, a running suture pad, and ring placement on a rocking peg board. After reaching proficiency, each resident was tested on a complex tissue closure task. For the next 8 weeks, the only robotic activity was biweekly virtual robotic skills maintenance. After 8 weeks, the residents performed the tissue closure task twice with the robot, followed by evaluation on the inanimate models used to reach proficiency. Repeated-measures statistical analyses were used to compare between the three tissue closure trials and between the final test at week 0 and the evaluation at week 8 for the other inanimate models. Time to complete the tissue closure task was more than 20 % lower for the second evaluation at 8 weeks than for the other two trials (p < 0.05). Residents maintained their skills for needle driving, but times for suture running and rocking peg board increased by more than 20 % at 8 weeks (p < 0.01). Virtual practice shows promise for maintaining robotic skills. Following a warm-up period, some skills may actually improve with biweekly virtual practice, but skill retention is selective, so further improvements are needed.

Endometrial cancer survivors' assessment of the benefits of exercise.

OBJECTIVE: The majority of women who have had endometrial cancer remain at risk for obesity related diseases. The social cognitive theory was used to explore their beliefs about exercise to aid in the development of effective interventions. METHODS: Women who had been treated for Stage I endometrial cancer were asked about their level of exercise to determine if they had been exercising regularly for more than 6 months (exercisers vs non-exercisers). They were asked to rate the likelihood that exercise would result in various health outcomes (expectations) and to rate the importance of these outcomes (expectancies). Scores for how likely exercise would result in an outcome of importance were calculated. Height and weight were obtained from nurses for calculation of BMI. Statistics were conducted using SPSS v 15. RESULTS: There were 106 valid questionnaires (86% participation rate); 41% were exercisers. Mean BMI was significantly lower in exercisers (31.6 ± 1.2 vs. 37.3 ± 1.2, p=0.001); a significantly greater proportion reported not having diabetes, heart disease or hypertension (69.8% vs. 49.2%, p=0.035). Exercisers were significantly more likely to report that feeling better physically and emotionally versus reducing the risk of diseases were likely and important outcomes of exercise (18.2 ± 0.8 vs 15.0 ± 1.0, p=0.002). CONCLUSIONS: Exercisers identified outcomes of exercise that are more immediate and subjective as being important and likely outcomes of exercise. Focusing on these aspects of exercise (feeling better physically and emotionally) may aid in the development of effective interventions for non-exercisers.

Robotic surgical skills: acquisition, maintenance, and degradation.

BACKGROUND AND OBJECTIVES: The degradation in robotic skills that occurs during periods of robotic surgical inactivity in newly trained surgeons was measured. The role of animate training in robotic skill was also assessed. METHODS: Robotically naive resident and attending surgeons underwent training with the da Vinci robot on needle passage (DN), rocking ring transfer peg board (RPB), and running suture pod tasks (SP). Errors were established to convert actual time to adjusted time. Participants were deemed "proficient" once their adjusted times were within 80% of those set by experienced surgeons through repeated trials. Participants did not use the robot except for repeating the tasks once at 4, 8, and 12 weeks (tests). Participants then underwent animate training and completed a final test within 7 days. RESULTS: Twenty-five attending and 29 resident surgeons enrolled; 3 withdrew. There were significant increases in time to complete each of the tasks, and in errors, by 4 weeks (Adjusted times: DN: 122.9 +/- 2.2 to 204.2 +/- 11.7, t = 6.9, P < .001; RPB: 262.4 +/- 2.5 to 364.7 +/- 8.0, t = 12.4, P < .001; SP: 91.4 +/- 1.4 to 169.9 +/- 6.8, t = 11.3, P < .001). Times decreased following animate training, but not to levels observed after proficiency training for the RPB and SP modules. CONCLUSIONS: Robotic surgical skills degrade significantly within 4 weeks of inactivity in newly trained surgeons. Animate training may provide different skills than those acquired in the dry lab.

A rare case of carcinosarcoma of the fallopian tube presenting with torsion, rupture and hemoperitoneum.

► Fallopian tube carcinosarcomas may present emergently with hemoperitoneum. ► Fallopian tube carcinosarcomas may be detected better with MR than with CT. ► Heterologous fallopian tube carcinosarcomas have been reported more often than the homologous type.

Polymorphism in the IL18 gene and epithelial ovarian cancer in non-Hispanic white women.

Over 22,000 cases of ovarian cancer were diagnosed in 2007 in the United States, but only a fraction of them can be attributed to mutations in highly penetrant genes such as BRCA1. To determine whether low-penetrance genetic variants contribute to ovarian cancer risk, we genotyped 1,536 single nucleotide polymorphisms (SNP) in several candidate gene pathways in 848 epithelial ovarian cancer cases and 798 controls in the North Carolina Ovarian Cancer Study (NCO) using a customized Illumina array. The inflammation gene interleukin-18 (IL18) showed the strongest evidence for association with epithelial ovarian cancer in a gene-by-gene analysis (P = 0.002) with a <25% chance of being a false-positive finding (q value = 0.240). Using a multivariate model search algorithm over 11 IL18 tagging SNPs, we found that the association was best modeled by rs1834481. Further, this SNP uniquely tagged a significantly associated IL18 haplotype and there was an increased risk of epithelial ovarian cancer per rs1834481 allele (odds ratio, 1.24; 95% confidence interval, 1.06-1.45). In a replication stage, 12 independent studies from the Ovarian Cancer Association Consortium (OCAC) genotyped rs1834481 in an additional 5,877 cases and 7,791 controls. The fixed effects estimate per rs1834481 allele was null (odds ratio, 0.99; 95% confidence interval, 0.94-1.05) when data from the 12 OCAC studies were combined. The effect estimate remained unchanged with the addition of the initial North Carolina Ovarian Cancer Study data. This analysis shows the importance of consortia, like the OCAC, in either confirming or refuting the validity of putative findings in studies with smaller sample sizes. (Cancer Epidemiol Biomarkers Prev 2008;17(12):3567-72).

Baseline characteristics influencing quality of life in women undergoing gynecologic oncology surgery.

BACKGROUND: Quality of life (QoL) measurements are important in evaluating cancer treatment outcomes. Factors other than cancer and its treatment may have significant effects on QoL and affect assessment of treatments. Baseline data from longitudinal studies of women with endometrial or ovarian cancer or adnexal mass determined at surgery to be benign were analyzed to determine the degree to which QoL is affected by baseline differences in demographic variables and health. METHODS: This study examined the effect of independent variables on domains of the Functional Assessment of Cancer Therapy (FACT-G) pre-operatively in gynecologic oncology patients undergoing surgery for pelvic mass suspected to be malignant or endometrial cancer. Patients also completed the Short Form Medical Outcomes Survey (SF-36) questionnaire (a generic health questionnaire that measures physical and mental health). Independent variables were surgical diagnosis (ovarian or endometrial cancer, benign mass), age, body mass index (BMI), educational level, marital status, smoking status, physical (PCS) and mental (MCS) summary scores of the SF-36. Multiple regression analysis was used to determine the influence of these variables on FACT-G domain scores (physical, functional, social and emotional well-being). RESULTS: Data were collected on 157 women at their pre-operative visit (33 ovarian cancer, 45 endometrial cancer, 79 determined at surgery to be benign). Mean scores on the FACT-G subscales and SF-36 summary scores did not differ as a function of surgical diagnosis. PCS, MCS, age, and educational level were positively correlated with physical well-being, while increasing BMI was negatively correlated. Functional well-being was positively correlated with PCS and MCS and negatively correlated with BMI. Social well-being was positively correlated with MCS and negatively correlated with BMI and educational level. PCS, MCS and age were positively correlated with emotional well-being. Models that included PCS and MCS accounted for 30 to 44% of the variability in baseline physical, emotional, and functional well-being on the FACT-G. CONCLUSION: At the time of diagnosis and treatment, patients' QoL is affected by inherent characteristics. Assessment of treatment outcome should take into account the effect of these independent variables. As treatment options become more complex, these variables are likely to be of increasing importance in evaluating treatment effects on QoL.

Surgical treatments for vulvar and vaginal dysplasia: a randomized controlled trial.

OBJECTIVE: To compare pain, adverse effects and recurrence of dysplasia in patients with vaginal intraepithelial neoplasia or vulvar intraepithelial neoplasia prospectively treated by carbon dioxide laser or ultrasonic surgical aspiration. METHODS: Patients were randomly assigned to receive treatment by laser or ultrasonic surgical aspiration from 2000-2005. Preoperative biopsy was done to confirm presence of dysplasia. Patients completed a visual analog scale regarding pain and were evaluated at 2-4 weeks to assess scarring, wound healing, and adverse effects. Patients returned every 3 months for 1 year for pelvic examination and cytology to assess recurrence. Follow-up colposcopy and biopsy were used at the discretion of the treating physician. Student t test, chi2, analysis of variance and multiple logistic regression were used for analysis. RESULTS: One hundred ten patients were randomly assigned. Ninety-six (87.3%) patients completed 1 year follow-up. Mean age of patients was 48.5 years. Mean visual analog scale score was significantly lower in patients treated by ultrasonic surgical aspiration (20.7 compared with 35.1; P=.032). For patients with vulvar lesions, there was less scarring with ultrasonic surgical aspiration (P<.01). Recurrence overall was 25% and was similar for ultrasonic surgical aspiration compared with laser (relative risk 0.96, 95% confidence interval 0.64-1.50, number needed to treat 95.6). Recurrence was associated with younger age (P<.01). CONCLUSION: Patients treated with ultrasonic surgical aspiration for vulvar and vaginal dysplasia reported less postoperative pain. Vulvar scarring was more common in patients treated by the laser. There was no difference in recurrence of dysplasia during a 1-year follow-up period between the two surgical modalities. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00394758 LEVEL OF EVIDENCE: I.

Body weight and composition changes in ovarian cancer patients during adjuvant chemotherapy.

OBJECTIVE: To prospectively examine body weight changes in women with newly diagnosed ovarian cancer receiving surgery and adjuvant chemotherapy. Body composition was examined in a subset of these women. METHODS: Body weight (BW) and body composition, using bioelectrical impedance (RJL Systems Inc.), were prospectively measured pre- and post-operatively, and at 3, 6, and 12 months. RESULTS: Mean age of 42 women was 59 years and did not differ by stage of disease. Nine women with early stage disease did not receive adjuvant chemotherapy. Mean BW of 33 patients receiving chemotherapy decreased from the pre- to post-operative visit and then returned to baseline levels by 12 months (F = 8.70, P = 0.003). Nine patients who did not receive chemotherapy demonstrated a similar pattern (F = 7.0, P = 0.002). Women receiving chemotherapy with stage I/II cancer had a 2.8 +/- 2.0 kg weight gain over the year, and women with stage III/IV cancer had a 1.5 +/- 1.5 kg weight loss (t = 1.72, P = 0.096). A subset of women with stage I/II (n = 6) and stage III/IV (n = 6) ovarian cancer receiving chemotherapy had body composition measured at three time points. Absolute body fat changes paralleled changes in BW (F = 9.95, P = 0.002). CONCLUSIONS: Our study is the first prospective evaluation of body weight and composition in women undergoing surgery and chemotherapy for ovarian cancer. These results demonstrate that women undergoing surgery for ovarian cancer lost weight following surgery and regained it slowly over the following year. Further investigations of weight changes during adjuvant chemotherapy are indicated to assess potential changes in different stages of disease.

Longitudinal assessment of quality of life and lifestyle in newly diagnosed ovarian cancer patients: the roles of surgery and chemotherapy.

OBJECTIVES: To prospectively evaluate quality of life (QoL), use of complementary and alternative medicine (CAM), and diet/exercise changes in ovarian cancer patients during the first 6 months following diagnosis. METHODS: Patients with newly diagnosed ovarian cancer were enrolled pre- or post-operatively and surveyed at 3 and 6 months. The Functional Assessment of Cancer Therapy (FACT-G), Medical Outcomes Survey (SF-36), and CAM/diet/exercise questionnaires were used. Independent samples t test and repeated measures ANOVA were used. RESULTS: Forty-two patients underwent surgical debulking and staging prior to chemotherapy. Patients completing the initial surveys post-operatively had significantly lower physical FACT-G and SF-36 physical scores compared to patients completing the surveys pre-operatively. In patients completing the baseline survey pre-operatively, there was a decrease in physical scores at 3 months (after surgery and during chemotherapy). There was no change observed at 3 months relative to baseline when patients completed the baseline survey post-operatively. Increases in physical and functional well-being were seen at 6 months relative to 3 months. There were no changes in emotional or social scores over time. CAM use increased over time; main reasons were to improve QoL and relieve symptoms. Alterations in diet and exercise were not seen. CONCLUSIONS: These data highlight the need to conduct assessments before and after surgery to identify effects due to surgery and/or chemotherapy. Patients may be using CAM during chemotherapy to deal with symptoms and compensate for decreased QoL. Intervention trials should be implemented to increase QoL following surgery and during adjuvant chemotherapy.

The impact of obesity and age on quality of life in gynecologic surgery.

OBJECTIVE: This study was undertaken to prospectively evaluate the effect of early stage endometrial cancer, age, and obesity on quality of life (QOL). STUDY DESIGN: Women undergoing surgery for endometrial cancer or an adnexal mass determined at surgery to be benign (controls) were enrolled preoperatively and followed for 6 months. RESULTS: Seventy-nine women completed the study. Functional Assessment of Cancer Therapy (FACT-G) scores increased significantly in all women; however, significant differences by patient weight and age were obtained. Obesity was associated with decreased physical FACT-G and SF-36 scores. Older women had lower SF-36 physical scores, higher emotional scores, and less change over time. CONCLUSION: Women with early endometrial cancer had similar changes in QOL as those who received surgery for benign disease. Obese and elderly women had domain alterations. Given the aging population and rising incidence of obesity, these results emphasize the need for QOL interventions in postoperative gynecologic care of these patients.

Effect of method of administration on longitudinal assessment of quality of life in gynecologic cancer: an exploratory study.

BACKGROUND: Longitudinal assessments of quality of life are needed to measure changes over the course of a disease and treatment. Computer versions of quality of life instruments have increased the feasibility of obtaining longitudinal measurements. However, there remain occasions when patients are not able to complete these questionnaires. This study examined whether changes measured using a computer version of the Functional Assessment of Cancer Therapy - General (FACT-G) on two occasions would be obtained if patients completed a paper version on one of the two occasions. METHODS: Gynecologic oncology patients completed a computer version of the FACT-G pre-operatively and at six months. Patients were given the option of using the paper version instead of the computer at either time point. Repeated measures analysis of variance was used. RESULTS: One hundred nineteen patients completed the FACT-G at both time points. Seventy-one (60%) patients used the computer at both visits, 26 (21.8%) used the computer followed by the paper version, 17 (14.3%) used the paper version followed by the computer version, and five patients (4.2%) used the paper version at both visits. Significant effects over time were obtained in the physical, functional, and emotional well-being domains, and in total scores, but there were no effects of method of administration of the questionnaires and no interaction between method of administration and changes over time. CONCLUSIONS: These data indicate that women are responding to the content of the questionnaire and not method of data collection. Although using the same method of administration of instruments over time is desirable, using alternate methods is preferable to forgoing data collection entirely. Large scale studies should be conducted to determine if the multiple methods of data collection that are becoming increasingly available are producing interchangeable information.