Accuracy of pre-operative tumor size assessment compared to final pathology and frequency of adjuvant treatment in patients with FIGO 2018 stage IB2 cervical cancer.

OBJECTIVE: The primary aim of our study was to compare tumor size assessment by pre-operative evaluation (physical examination and/or imaging) with tumor size on final pathology. As a secondary outcome, we evaluated the rate of adjuvant treatment in patients who underwent radical hysterectomy whose tumor size was ≥3 cm on final pathology. METHODS: Patient details were collected from three separate databases: the University of Texas MD Anderson Cancer Center Radical Hysterectomy Database, the SUCCOR Study Group Database, and the Multi-institutional Database LATAM (encompassing Latin America and Europe). Patients with International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IB2 cervical cancer on pre-operative evaluation (physical examination or imaging) who underwent radical hysterectomy with a therapeutic intent were included. Any histological subtype, any tumor grade, and pre-operative evaluation with clinical evaluation and/or imaging (ultrasound, MRI, CT, or PET/CT) was considered. RESULTS: A total of 675 patients met eligibility criteria (SUCCOR=350, LATAM=250, MD Anderson=75). The median age was 46 years (range 22-82) and the median body mass index was 25.6 kg/m2 (range 15.1-68). The most common histologic subtype was squamous carcinoma (68%, n=456), and the majority had either grade 2 or 3 disease . Overall pre-operative imaging modalities used were MRI (52%, n=352), ultrasound (21%, n=140), CT (5%, n=32), and PET/CT (1%, n=10). Most patients underwent open surgery (60%, n=404). In total, 113 (17%) patients had lymph node involvement and 58 (9%) patients had parametrial involvement. A total of 343 (51%) patients received adjuvant therapy, with the majority of those receiving chemoradiation (54%, n=186) followed by radiation alone (44%, n=152). The results of the Bland-Altman analysis showed that pre-operative physical examination, MRI, ultrasound, and CT all overestimated tumor size, but only the bias found for physical examination (p<0.0001) and MRI (p=0.0102) were statistically significant. However, in patients who underwent a pre-operative MRI, a total of 293 (83.2%) patients with tumor size 2-4 cm by MRI had concordance with tumor measurement on final pathology. Similarly, when evaluating accuracy of physical examination with tumor size by MRI, we found that there was agreement in 319 (91.1%) patients. Similarly, we found that concordance of physical examination with tumor size on final pathology was 80.6%. There were 340 (50%) patients who had tumor size on pathology ≥3 cm, and 207 (61%) of these received adjuvant therapy. Additionally, there was a significantly higher incidence of positive lymph nodes with increasing tumor size on pathology (2-2.99 cm, 13% (29/222) vs 3-4 cm, 21% (66/316), p=0.022). CONCLUSIONS: Our study showed that there is a high concordance between tumor size assessment by physical examination and MRI, as well as estimates of measurement by MRI and final pathology. In addition, we noted that the majority of patients with FIGO 2018 stage IB2 received adjuvant therapy after radical hysterectomy.

Applicant and Program Director Perceptions of Second Look Events During the 2023 Radiation Oncology Residency Match.

Purpose: Virtual radiation oncology (RO) residency interviews may impair applicant and program evaluation. Second look events (SLEs) exist; however, the frequency, nature, and implications are unknown. We surveyed applicants and program directors (PDs) to characterize the 2023 RO Match SLEs and assess perspectives. Method and Materials: An online, anonymous survey was distributed to 2023 RO Match applicants and American College of Graduate Medical Education-accredited RO PDs post-Match. Number and percentage are reported as response per question. Likert-type scores (1, strongly agree; 5, strongly disagree) are reported as median, IQR. Results: Responses were received from 51 of 246 applicants (21%) and 52 of 88 PDs (59%). Forty applicants (87%) were offered in-person and virtual SLEs; 20 (51%) and 17 (44%) applicants were invited to 1 to 3 and 4 to 6 events, respectively. Most invited applicants attended none (21, 54%). Applicants reported that all (21, 54%) or some (16, 41%) programs communicated intentions to finalize rank order lists (ROLs) before SLEs. Most applicants (29, 74%) agreed that SLEs were optional without ROL consequences (median, 2, IQR 1-3). Applicants declined in-person SLEs due to city/facility indifference (10, 43%), finances (10, 43%), and logistics (9, 39%). Most (12, 86%) in-person SLE attendees agreed that SLEs influenced their ROL (median, 2, IQR 1-2). Nineteen PDs (40%) reported offering SLEs, with 18 of 19 being in-person. PDs who did not offer SLEs cited ethical concerns (13, 45%) and institutional policies (11, 38%). All PDs reported that SLEs were optional, and 18 of 19 explained that the SLE would be without ROL consequences. SLEs mostly occurred in February before (11, 58%) and after (15, 79%) ROL submission. Conclusions: In-person SLEs occurred during Match 2023. All PDs considered SLEs optional which was trusted by most applicants. Attendance at in-person SLEs influenced applicants' ROLs; however, finances and logistics impaired applicant attendance. Further work is needed to appreciate SLE implications and ensure equitable residency recruitment.

Sentinel lymph node mapping with indocyanine green using SPY-PHI in open radical hysterectomy or trachelectomy.

OBJECTIVE: To evaluate the detection rate of at least one sentinel lymph node (SLN) in patients with early cervical cancer who underwent open radical hysterectomy or trachelectomy using indocyanine green (ICG) with the SPY Portable Handler Imager (SPY-PHI) system. METHODS: We retrospectively reviewed patients with cervical cancer FIGO 2018 stage IA1 with lymphovascular invasion up to stage IIIC1p who underwent SLN mapping and open radical hysterectomy or trachelectomy from March 2018 through August 2022 at The University of Texas MD Anderson Cancer Center. ICG was the only tracer used with the SPY-PHI system. Patient demographics, surgical approach, and tumor factors were analyzed. Overall detection, bilateral detection, and empty lymph node packet rates were determined. RESULTS: A total of 106 patients were included. Ninety-four (88.7%) patients underwent open radical hysterectomy and 12 (11.3%) open radical trachelectomy. Median age was 40 years (range, 23-71). Median body mass index was 28.8 kg/m2 (range, 17.6-48.4). The most common FIGO 2018 stages were IB1 (35%) and IB2 (30%). The most common histologic subtypes were squamous cell carcinoma (45%) and adenocarcinoma (45%). Most patients had grade 2 disease (61%) and no lymphovascular invasion (58%). Median tumor size was 1.8 cm (range, 0.3-4). Median number of detected SLN was 4 (range, 0-12). An SLN was identified during surgery in 104 patients (98%), with bilateral mapping in 94 (89%) and unilateral mapping in 10 (9%). The empty lymph node packet rate was 4 (3.8%). The external iliac (73%) was the most common site of SLN detection. Fourteen patients had positive lymph nodes (13.5%); 3 (21.4%) had macrometastases, 9 (64.3%) had micrometastases, and 2 (14.3%) had isolated tumor cells. CONCLUSION: SLN mapping using ICG with the SPY-PHI system in open radical hysterectomy or trachelectomy is reliable and results in high overall and bilateral detection rates in patients with early cervical cancer.

Evaluation of a tiered opioid prescription algorithm in an ERAS pathway: exploring opportunities for further refinement.

BACKGROUND: Opioid over-prescription is wasteful and contributes to the opioid crisis. We implemented a personalized tiered discharge opioid protocol and education on opioid disposal to minimize over-prescription. OBJECTIVE: To evaluate the intervention by investigating opioid use post-discharge for women undergoing abdomino-pelvic surgery, and patient adherence to opioid disposal education. METHODS: We analyzed post-discharge opioid consumption among 558 patients. Eligible patients included those who underwent elective gynecologic surgery, were not taking scheduled opioids pre-operatively, and received discharge opioids according to a tiered prescribing algorithm. A survey assessing discharge opioid consumption and disposal safety knowledge was distributed on post-discharge day 21. Over-prescription was defined as >20% of the original prescription left over. Descriptive statistics were used for analysis. RESULTS: The survey response rate was 61% and 59% in the minimally invasive surgery and open surgery cohorts, respectively. Overall, 42.8% of patients reported using no opioids after hospital discharge, 45.2% in the minimally invasive surgery and 38.6% in the open surgery cohort. Furthermore, 74.9% of respondents were over-prescribed, with median age being statistically significant for this group (p=0.004). Finally, 46.4% of respondents expressed no knowledge regarding safe disposal practices, with no statistically significant difference between groups (p>0.99). CONCLUSION: Despite implementation of the tiered discharge opioid algorithm aimed to personalize opioid prescriptions to estimated need, we still over-prescribed opioids. Additionally, despite targeted education, nearly half of all patients who completed the survey did not know how to dispose of their opioid tablets. Additional efforts are needed to further refine the algorithm to reduce over-prescription of opioids and improve disposal education.

Social media use is associated with higher levels of anxiety and depression in patients with neuroendocrine carcinoma of the cervix: A NeCTuR study.

OBJECTIVE: Neuroendocrine cervical carcinoma (NECC) is rare. Educational resources are limited for NECC patients, leading many to seek information online through patient-led social networks. We sought to characterize the relationships between anxiety and depression levels and social media use among NECC patients. METHODS: Seven surveys assessing social media use, anxiety, and depression were distributed to living NECC patients enrolled in our NECC registry. The primary outcomes were associations between Social Network Time Use Scale (SONTUS) global score and Generalized Anxiety Disorder (GAD-7) and Center for Epidemiologic Studies Depression Scale (CESD) total scores. RESULTS: Eighty-eight patients enrolled; 81 who completed at least 1 survey were included. Ninety-seven percent (70/72) of patients completing SONTUS were low-to-average social media users. Seventy-four percent (53/72) of patients visited a patient-led NECC support-group page on Facebook within the past 4 weeks, and of those, 79% (42/53) reported receiving useful information. Among the patients who did not visit the page, 47% (9/19) reported that the page elicited anxiety and/or sadness. The mean GAD-7 and CES-D scores for the entire cohort were 7.3 and 18.1, respectively. The Spearman correlations between social media use and these scores were significant (GAD-7: 0.23 [p = 0.05]; CESD: 0.25 [p = 0.04]). The estimated odds ratios for moderate/severe anxiety and depression as a function of SONTUS global score were 1.26 (95% CI 1.03-1.55; p = 0.03) and 1.23 (95% CI 1.01-1.49; p = 0.04), respectively. CONCLUSIONS: NECC patients demonstrated low-to-average social media use and relatively high anxiety and depression. Increased social media use was associated with elevated anxiety and depression.

Exercise Training Reduces the Inflammatory Response and Promotes Intestinal Mucosa-Associated Immunity in Lynch Syndrome.

PURPOSE: Lynch syndrome (LS) is a hereditary condition with a high lifetime risk of colorectal and endometrial cancers. Exercise is a non-pharmacologic intervention to reduce cancer risk, though its impact on patients with LS has not been prospectively studied. Here, we evaluated the impact of a 12-month aerobic exercise cycling intervention in the biology of the immune system in LS carriers. PATIENTS AND METHODS: To address this, we enrolled 21 patients with LS onto a non-randomized, sequential intervention assignation, clinical trial to assess the effect of a 12-month exercise program that included cycling classes 3 times weekly for 45 minutes versus usual care with a one-time exercise counseling session as control. We analyzed the effects of exercise on cardiorespiratory fitness, circulating, and colorectal-tissue biomarkers using metabolomics, gene expression by bulk mRNA sequencing, and spatial transcriptomics by NanoString GeoMx. RESULTS: We observed a significant increase in oxygen consumption (VO2peak) as a primary outcome of the exercise and a decrease in inflammatory markers (prostaglandin E) in colon and blood as the secondary outcomes in the exercise versus usual care group. Gene expression profiling and spatial transcriptomics on available colon biopsies revealed an increase in the colonic mucosa levels of natural killer and CD8+ T cells in the exercise group that were further confirmed by IHC studies. CONCLUSIONS: Together these data have important implications for cancer interception in LS, and document for the first-time biological effects of exercise in the immune system of a target organ in patients at-risk for cancer.

Remotely Delivered Cancer Genetic Testing in the Making Genetic Testing Accessible (MAGENTA) Trial: A Randomized Clinical Trial.

Importance: Requiring personalized genetic counseling may introduce barriers to cancer risk assessment, but it is unknown whether omitting counseling could increase distress. Objective: To assess whether omitting pretest and/or posttest genetic counseling would increase distress during remote testing. Design, Setting, and Participants: Making Genetic Testing Accessible (MAGENTA) was a 4-arm, randomized noninferiority trial testing the effects of individualized pretest and/or posttest genetic counseling on participant distress 3 and 12 months posttest. Participants were recruited via social and traditional media, and enrollment occurred between April 27, 2017, and September 29, 2020. Participants were women aged 30 years or older, English-speaking, US residents, and had access to the internet and a health care professional. Previous cancer genetic testing or counseling was exclusionary. In the family history cohort, participants had a personal or family history of breast or ovarian cancer. In the familial pathogenic variant (PV) cohort, participants reported 1 biological relative with a PV in an actionable cancer susceptibility gene. Data analysis was performed between December 13, 2020, and May 31, 2023. Intervention: Participants completed baseline questionnaires, watched an educational video, and were randomized to 1 of 4 arms: the control arm with pretest and/or posttest genetic counseling, or 1 of 3 study arms without pretest and posttest counseling. Genetic counseling was provided by phone appointments and testing was done using home-delivered saliva kits. Main Outcomes and Measures: The primary outcome was participant distress measured by the Impact of Event Scale 3 months after receiving the results. Secondary outcomes included completion of testing, anxiety, depression, and decisional regret. Results: A total of 3839 women (median age, 44 years [range 22-91 years]), most of whom were non-Hispanic White and college educated, were randomized, 3125 in the family history and 714 in the familial PV cohorts. In the primary analysis in the family history cohort, all experimental arms were noninferior for distress at 3 months. There were no statistically significant differences in anxiety, depression, or decisional regret at 3 months. The highest completion rates were seen in the 2 arms without pretest counseling. Conclusions and Relevance: In the MAGENTA clinical trial, omitting individualized pretest counseling for all participants and posttest counseling for those without PV during remote genetic testing was not inferior with regard to posttest distress, providing an alternative care model for genetic risk assessment. Trial Registration: ClinicalTrials.gov Identifier: NCT02993068.

An Accessible Communication System for Population-Based Genetic Testing: Development and Usability Study.

BACKGROUND: Genetic testing uptake is low, despite the well-established connection between pathogenic variants in certain cancer-linked susceptibility genes and ovarian cancer risk. Given that most major insurers cover genetic testing for those with a family history suggestive of hereditary cancer, the issue may lie in access to genetic testing. Remotely accessible web-based communication systems may improve awareness, and uptake, of genetic testing services. OBJECTIVE: This study aims to present the development and formative evaluation of the multistep web-based communication system required to support the implementation of, and access to, genetic testing. METHODS: While designing the multistep web-based communication system, we considered various barriers and facilitators to genetic testing, guided by dimensions of accessibility. In addition to conducting usability testing, we performed ongoing assessments focusing on the function of the web-based system and participant response rates, with the goal of continuing to make modifications to the web-based communication system as it is in use. RESULTS: The combined approach of usability testing and expert user experience consultation resulted in several modifications to the multistep web-based communication system, including changes that related to imagery and content, web accessibility, and general organization of the web-based system. All recommendations were made with the goal of improving the overall accessibility of the web-based communication system. CONCLUSIONS: A multistep web-based communication system appears to be an effective way to address many potential barriers to access, which may otherwise make genetic testing difficult for at-risk individuals to participate in. Importantly, some dimensions of access were easy to assess before study recruitment, but other aspects of the communication system required ongoing assessment during the implementation process of the Making Genetic Testing Accessible study.

A Cross-Sectional Study of the Prevalence of Anal Dysplasia among Women with High-Grade Cervical, Vaginal, and Vulvar Dysplasia or Cancer: The PANDA Study.

BACKGROUND: High-risk human papillomavirus (HR-HPV) infection is a risk factor for anal cancer, yet no anal cancer screening guidelines exist for women with lower genital tract HPV-related disease. We sought to describe the prevalence of anal HR-HPV or cytologic abnormalities in such women. METHODS: This cross-sectional study was performed between October 2018 and December 2021. Inclusion criteria were ≥21 years of age and a prior diagnosis of high-grade dysplasia/cancer of the cervix, vagina, or vulva. Participants underwent anal cytology and anal/cervicovaginal HR-HPV testing. Women with abnormal anal cytology were referred for high-resolution anoscopy (HRA). RESULTS: 324 evaluable women were enrolled. Primary diagnosis was high-grade dysplasia/cancer of the cervix (77%), vagina (9%), and vulva (14%). Anal HR-HPV was detected in 92 patients (28%) and included HPV-16 in 24 (26%), HPV-18 in 6 (7%), and other HR-HPV types in 72 (78%) patients. Anal cytology was abnormal in 70 patients (23%) and included atypical squamous cells of undetermined significance (80%), low-grade squamous intraepithelial lesion (9%), high-grade intraepithelial lesion (HSIL; 1%), and atypical squamous cells-cannot rule out HSIL (10%). Of these patients, 55 (79%) underwent HRA. Anal biopsies were performed in 14 patients: 2 patients had anal intraepithelial neoplasia (AIN) 2/3, 1 patient had AIN 1, and 11 patients had negative biopsies. Both patients with AIN 2/3 had a history of cervical dysplasia. CONCLUSIONS: Our results suggest an elevated risk of anal HR-HPV infection and cytologic abnormalities in women with lower genital tract dysplasia/cancer. IMPACT: These results add to the growing body of evidence suggesting the need for evaluation of screening methods for anal dysplasia/cancer in this patient population to inform evidence-based screening recommendations.

Using Social Media to Facilitate Communication About Women's Testing: Tool Validation Study.

BACKGROUND: Strong participant recruitment practices are critical to public health research but are difficult to achieve. Traditional recruitment practices are often time consuming, costly, and fail to adequately target difficult-to-reach populations. Social media platforms such as Facebook are well-positioned to address this area of need, enabling researchers to leverage existing social networks and deliver targeted information. The MAGENTA (Making Genetic Testing Accessible) study aimed to improve the availability of genetic testing for hereditary cancer susceptibility in at-risk individuals through the use of a web-based communication system along with social media advertisements to improve reach. OBJECTIVE: This paper is aimed to evaluate the effectiveness of Facebook as an outreach tool for targeting women aged ≥30 years for recruitment in the MAGENTA study. METHODS: We designed and implemented paid and unpaid social media posts with ongoing assessment as a primary means of research participant recruitment in collaboration with patient advocates. Facebook analytics were used to assess the effectiveness of paid and unpaid outreach efforts. RESULTS: Over the course of the reported recruitment period, Facebook materials had a reach of 407,769 people and 57,248 (14.04%) instances of engagement, indicating that approximately 14.04% of people who saw information about the study on Facebook engaged with the content. Paid advertisements had a total reach of 373,682. Among those reached, just <15% (54,117/373,682, 14.48%) engaged with the page content. Unpaid posts published on the MAGENTA Facebook page resulted in a total of 34,087 reach and 3131 instances of engagement, indicating that around 9.19% (3131/34,087) of people who saw unpaid posts engaged. Women aged ≥65 years reported the best response rate, with approximately 43.95% (15,124/34,410) of reaches translating to engagement. Among the participants who completed the eligibility questionnaire, 27.44% (3837/13,983) had heard about the study through social media or another webpage. CONCLUSIONS: Facebook is a useful way of enhancing clinical trial recruitment of women aged ≥30 years who have a potentially increased risk for ovarian cancer by promoting news stories over social media, collaborating with patient advocacy groups, and running paid and unpaid campaigns. TRIAL REGISTRATION: ClinicalTrials.gov NCT02993068; https://clinicaltrials.gov/ct2/show/NCT02993068.

A phase II randomized double blinded trial evaluating the efficacy of curcumin with pre-operative chemoradiation for rectal cancer.

Background: In vivo studies demonstrate that curcumin increases radioresponse of colorectal cancers. To demonstrate efficacy in humans, we performed a randomized double-blind study of locally advanced rectal cancer (LARC) patients receiving pre-operative chemoradiation therapy (CRT) ± curcumin. We used pathologic complete response (pCR) rate as a surrogate for clinical outcome. Methods: From 2008-2010, LARC patients were randomized to placebo/curcumin in a 1:2 ratio. Patients received CRT [50.4 gray in 28 fractions; capecitabine (825 mg/m2 twice daily)] followed by surgery. Curcumin (4 grams orally, twice daily) or placebo was given throughout CRT and 6 weeks afterward. Toxicity was monitored weekly. Blood samples taken pre- and 1-hour post-ingestion and tissue biopsies (both collected at CRT week 2) were analyzed for pharmacokinetics. The primary outcome was surgical pCR rate. Results: Of 22 enrolled patients, 15 received curcumin. Median age was 61 years and the majority were male (n=13; 59%). The median serum curcumin concentrations before (3.04 ng/mL; range, 1.24-18.88 ng/mL) and 1 hour after (3.32 ng/mL; range, 0.84-5.36 ng/mL) curcumin intake did not differ significantly (P=0.33). Serum curcumin concentrations both increased and decreased 1-hour post-administration (range as percentage of baseline: 8.8-258.1%). Twelve curcumin patient tissue biopsies had median curcumin concentration of 33.7 ng/mg tissue (range, 0.1-4,765.7 ng/mg). Two placebo and 1 curcumin patient achieved pCRs (P=0.18). One grade 3 toxicity (infection) was experienced. Conclusions: The addition of curcumin to CRT did not increase pCR rates for LARC patients. The unpredictable bioavailability of curcumin contributes to continued uncertainties regarding curcumin efficacy. Trial Registration: ClinicalTrials.gov identifier: NCT00745134.

Thirty-day hospital readmission rate, reasons, and risk factors after acute inpatient cancer rehabilitation.

OBJECTIVES: To evaluate the 30-day hospital readmission rate, reasons, and risk factors for patients with cancer who were discharged to home setting after acute inpatient rehabilitation. DESIGN, SETTING, AND PARTICIPANTS: This was a secondary retrospective analysis of participants in a completed prospective survey study that assessed the continuity of care and functional safety concerns upon discharge and 30 days after discharge in adults. Patients were enrolled from September 5, 2018, to February 7, 2020, at a large academic quaternary cancer center with National Cancer Institute Comprehensive Cancer Center designation. MAIN OUTCOMES AND MEASURES: Thirty-day hospital readmission rate, descriptive summary of reasons for readmissions, and statistical analyses of risk factors related to readmission. RESULTS: Fifty-five (21%) of the 257 patients were readmitted to hospital within 30 days of discharge from acute inpatient rehabilitation. The reasons for readmissions were infection (20, 7.8%), neoplasm (9, 3.5%), neurological (7, 2.7%), gastrointestinal disorder (6, 2.3%), renal failure (3, 1.1%), acute coronary syndrome (3, 1.1%), heart failure (1, 0.4%), fracture (1, 0.4%), hematuria (1, 0.4%), wound (1, 0.4%), nephrolithiasis (1, 0.4%), hypervolemia (1, 0.4%), and pain (1, 0.4%). Multivariate logistic regression modeling indicated that having a lower locomotion score (OR = 1.29; 95% CI, 1.07-1.56; p = 0.007) at discharge, having an increased number of medications (OR = 1.12; 95% CI, 1.01-1.25; p = 0.028) at discharge, and having a lower hemoglobin at discharge (OR = 1.31; 95% CI, 1.03-1.66; p = 0.031) were independently associated with 30-day readmission. CONCLUSION AND RELEVANCE: Among adult patients with cancer discharged to home setting after acute inpatient rehabilitation, the 30-day readmission rate of 21% was higher than that reported for other rehabilitation populations but within the range reported for patients with cancer who did not undergo acute inpatient rehabilitation.

A prospective randomized trial comparing liposomal bupivacaine vs standard bupivacaine wound infiltration in open gynecologic surgery on an enhanced recovery pathway.

BACKGROUND: Value in healthcare is reflected by patient-centered outcomes of care per health dollar expended. Although liposomal bupivacaine is more expensive, it has been shown to provide prolonged analgesia (up to 72 hours). OBJECTIVE: This study aimed to evaluate whether the addition of liposomal bupivacaine to standard bupivacaine could decrease opioid intake and improve pain control after laparotomy for gynecologic surgery compared with standard bupivacaine alone in an enhanced recovery after surgery pathway. STUDY DESIGN: A prospective randomized controlled single-blinded trial of wound infiltration with liposomal bupivacaine plus 0.25% bupivacaine (study arm) vs 0.25% bupivacaine (control arm) was performed at a National Cancer Institute-designated tertiary referral cancer center. Participants were patients aged ≥18 years undergoing exploratory laparotomy for a gynecologic indication. All patients were treated on an enhanced recovery pathway including local wound infiltration before closure. In this study, 266 mg of liposomal bupivacaine (free base; equal to 300 mg bupivacaine HCL)+150 mg of bupivacaine mixed in the same syringe was used in the study arm, and 150 mg of bupivacaine was used in the control arm. The primary outcome was the proportion of patients who were opioid-free within 48 hours after surgery. Secondary outcomes included number of opioid-free days from postoperative day 0 to postoperative day 3, days to first opioid administration, morphine equivalent daily dose, and patient-reported outcomes collected with the MD Anderson Symptom Inventory. The MD Anderson Symptom Inventory was administered as a preoperative baseline, daily while hospitalized, and at least weekly for 8 weeks after discharge. All outcomes were prespecified before data collection. RESULTS: In this study, 102 patients were evaluated. Among them, 16.7% of patients in the study arm received no opioids up to 48 hours compared with 14.8% in the control arm (P=.99). There were no significant differences in the amount of intraoperative opioids administered or days to first opioid use. There was no significant difference between the 2 arms in median cumulative morphine equivalent daily dose (21.3 [study arm] vs 33.8 [control arm]; P=.36) or between the groups in morphine equivalent daily dose per individual day. There were no significant differences in patient-reported pain or interference with walking between the 2 arms or other patient-reported outcomes. CONCLUSION: Within an enhanced recovery after surgery pathway, adding liposomal bupivacaine to 0.25% bupivacaine wound infiltration did not decrease the proportion of patients who were opioid-free within 48 hours after surgery, did not decrease opioid intake, or did not improve patient's self-reported pain and functional recovery compared with standard bupivacaine.

MAGENTA (Making Genetic testing accessible): a prospective randomized controlled trial comparing online genetic education and telephone genetic counseling for hereditary cancer genetic testing.

BACKGROUND: Studies have consistently indicated that the majority of individuals meeting the US Prevention Services Task Force guidelines for genetic testing have not had genetic counseling or testing. Despite increased availability and lower costs of multiplex cancer gene panels, there remains a gap in genetics services that has not been addressed by the current care delivery models. Lower cost of DNA sequencing with online patient-initiated ordering could increase test availability, but the ideal quantity and delivery method of patient education is not known. We hypothesized that online genetic education and testing with access to board certified genetic counselors could improve access to genetic testing while maintaining test quality and clinical utility. The MAGENTA (MAking GENetic Testing Accessible) trial is a nationwide randomized study designed to compare the effectiveness of online genetic education with pre- and post-test telephone genetic counseling to three potentially more accessible alternative approaches: online genetic education with optional telephone counseling, online genetic education with required pre-test telephone genetic counseling, and online genetic education with required post-test telephone genetic counseling. METHODS: 3000 women nationwide will undergo genetic testing for 19 hereditary cancer genes. This is a randomized four-arm non-inferiority study with equal randomization. The four study arms were selected to independently assess the delivery of genetic information both before and after genetic testing (pre-test and post-test) by either requiring telephone genetic counseling or providing only online education with optional telephone counseling. Patients have post-test telephone counseling when testing positive for a pathogenic inherited mutation in all four arms. Surveys measuring psychological, behavioral and cognitive state are completed online at baseline, 3 months, 12 months and 24 months post-results disclosure. The primary study outcome is cancer-risk distress at 3 months post-result disclosure. DISCUSSION: This trial will assess the use of a genetic service model using online access and electronic education, while evaluating the need for personal pre- and post-test genetic counseling. Data from this study may lead to increased options for delivery of genetic testing and possibly increase access to genetic testing. Identifying more individuals with inherited cancer susceptibility will allow targeted cancer prevention. TRIAL REGISTRATION: Clinicaltrials.gov: NCT02993068 (registered December 14, 2016).

Cellular Oxidative Stress in Pediatric Leukemia and Lymphoma Patients Undergoing Treatment Is Associated with Protein Consumption.

Over and under nutrition are associated with worse outcomes for children with leukemia and lymphoma; however, the molecular basis for this clinical observation is not well understood. Many chemotherapeutics used for leukemia treatment are known to generate oxidative stress in vitro; therefore, we evaluated redox status and diet in pediatric leukemia patients during therapy in order to ascertain relationships between nutrition and oxidative stress. Dietary intake and redox measures in peripheral blood mononuclear cells from 32 pediatric leukemia and lymphoma patients were collected over six months during treatment. Baseline measures when patients were off chemotherapy and subsequent assessments were collected after one, two and six months. Oxidative stress increased over time in all patients, consistent with chemotherapy-induced redox effects. Older and younger children showed significantly different baseline levels of reactive oxygen species, which increased over time in all age ranges. Diet was assessed at points proximal to oxidative stress measurements and revealed a novel association with consumption of animal protein, vegetable protein, and total protein intake. Our findings demonstrate that chemotherapy increases oxidative stress in pediatric leukemia patients, and raises the possibility that dietary protein or altered protein metabolism could contribute to clinical outcomes.

The influence of surgeon volume on outcomes after pelvic exenteration for a gynecologic cancer.

OBJECTIVE: To determine the effect of surgeon experience on intraoperative, postoperative and long-term outcomes among patients undergoing pelvic exenteration for gynecologic cancer. METHODS: This was a retrospective analysis of all women who underwent exenteration for a gynecologic malignancy at MD Anderson Cancer Center, between January 1993 and June 2013. A logistic regression was used to model the relationship between surgeon experience (measured as the number of exenteration cases performed by the surgeon prior to a given exenteration) and operative outcomes and postoperative complications. Cox proportional hazards regression was used to model survival outcomes. RESULTS: A total of 167 exenterations were performed by 19 surgeons for cervix (78, 46.7%), vaginal (43, 25.8%), uterine (24, 14.4%), vulvar (14, 8.4%) and other cancer (8, 4.7%). The most common procedure was total pelvic exenteration (69.4%), incontinent urinary diversion (63.5%) and vertical rectus abdominis musculocutaneous reconstruction (42.5%). Surgical experience was associated with decreased estimated blood loss (p<0.001), intraoperative transfusion (p=0.009) and a shorter length of stay (p=0.03). No difference was noted in the postoperative complication rate (p=0.12-0.95). More surgeon experience was not associated with overall or disease specific survival: OS (hazard ratio [HR]=1.02; 95% confidence interval [CI]=0.97-1.06; p=0.46) and DSS (HR=1.01; 95% CI=0.97-1.04; p=0.66), respectively. CONCLUSION: Patients undergoing exenteration by more experienced surgeons had improvement in intraoperative factors such as estimated blood loss, transfusion rates and length of stay. No difference was seen in postoperative complication rates, overall or disease specific survival.

Effect of an Enhanced Recovery After Surgery Program on Opioid Use and Patient-Reported Outcomes.

OBJECTIVE: To investigate the effect of an enhanced recovery after surgery (ERAS) program on perioperative outcomes with an emphasis on opioid consumption and patient-reported outcomes in the immediate and extended postoperative periods. METHODS: We initiated our ERAS program as part of a quality improvement initiative in November 2014. We compared clinical outcomes among a cohort of 607 women undergoing open gynecologic surgery before or after implementation of ERAS. For 293 patients, patient-reported outcomes were compared using the MD Anderson Symptom Inventory-Ovarian Cancer. RESULTS: Median age was 58 years (range 18-85 years). Median length of stay decreased by 25% for patients in the ERAS pathway (P<.001). Overall, patients in the ERAS group had a 72% reduction in median opioid consumption and 16% were opioid-free during admission up to postoperative day 3 (P<.001). There was no difference in pain scores (P=.80). Patients on ERAS reported less fatigue (P=.01), interference with walking (P=.003), and total interference (composite score of physical and affective measures) during hospitalization (P=.008). After discharge, those on the ERAS pathway demonstrated a significantly shorter median time to return to no or mild fatigue (10 vs 30 days, P=.03), mild or no interference with walking (5 vs 13 days, P=.003), and mild to no total interference (3 vs 13 days, P=.02). There were no significant differences in complications, rates of readmission, or reoperation between the pre- and post-ERAS groups. CONCLUSION: Implementation of an ERAS program was associated with significantly decreased opioid use after surgery and improvement in key patient-reported outcomes associated with functional recovery after surgery without compromising pain scores.

Bilateral salpingectomy with delayed oophorectomy for ovarian cancer risk reduction: A pilot study in women with BRCA1/2 mutations.

OBJECTIVE: Risk-reducing salpingo-oophorectomy (RRSO) reduces ovarian cancer risk in BRCA1/2 mutation carriers, but the adverse effects of the associated early-onset surgical menopause are problematic. Despite suggestive evidence, no data demonstrate whether bilateral salpingectomy alone lowers the risk of developing ovarian cancer in BRCA mutation carriers. We conducted a pilot study of bilateral salpingectomy with delayed oophorectomy (BS/DO) in BRCA mutation carriers to determine the safety and acceptability of the procedure. METHODS: In this prospective, multicenter, non-randomized pilot study, pre-menopausal BRCA1/2 mutation carriers aged 30 to 47 years chose screening, RRSO, or BS/DO. For those undergoing BS/DO, the delayed oophorectomy was recommended at age 40 years for BRCA1 and age 45 years for BRCA2 patients. We compared surgical and psychosocial outcomes between time points and between arms. RESULTS: Of the 43 patients enrolled, 19 (44%) chose BS/DO, 12 (28%) chose RRSO, and 12 (28%) chose screening. The cohort was 37% BRCA1 carriers and 63% BRCA2 carriers. One serous tubal intraepithelial carcinoma (STIC) was found in an RRSO patient, and no cases of occult ovarian cancers were found. There were no surgical complications. Twelve months after surgery, responses on the Cancer Worry Scale indicated decreased worry in the BS/DO (P < 0.0001) and RRSO (P = 0.01) arms, while responses on the State Anxiety Inventory indicated decreased anxiety in the BS/DO arm (P = 0.02) compared with preoperative responses. CONCLUSIONS: In this pilot study, BRCA mutation carriers who underwent bilateral salpingectomy had no intraoperative complications, were satisfied with their procedure choice, and had decreased cancer worry and anxiety after the procedure.

Nuclear ß-catenin localization and mutation of the CTNNB1 gene: a context-dependent association.

Although the majority of low-grade, early-stage endometrial cancer patients have good survival with surgery alone, patients who recur tend to do poorly. Identification of patients at high risk of recurrence who would benefit from adjuvant treatment or more extensive surgical staging would help optimize individualized care of endometrial cancer patients. CTNNB1 (encodes ß-catenin) mutations identify a subset of low-grade, early-stage endometrial cancer patients at high risk of recurrence. Mutation of CTNNB1 exon 3 is classically associated with translocation of the ß-catenin protein from the membrane to the nucleus and activation of Wnt/ß-catenin signaling. Given the clinical utility of identifying endometrial carcinomas with CTNNB1 mutation, the purpose of this study was to determine if immunohistochemistry could act as a surrogate for CTNNB1 gene sequencing. Next-generation sequencing was performed on 345 endometrial carcinomas. Immunohistochemical localization of ß-catenin was determined for 53/63 CTNNB1 exon 3 mutant tumors for which tissue was available and a subset of wild-type tumors. Nuclear localization of ß-catenin had 100% specificity in distinguishing CTNNB1 mutant from wild type, but sensitivity was lower (84.9%). Nearly half of CTNNB1 mutant cases had only 5-10% of tumor cells with ß-catenin nuclear localization. The concordance between pathologists blinded to mutation status in assessing nuclear localization was 100%. The extent of ß-catenin nuclear localization was not associated with specific CTNNB1 gene mutation, tumor grade, presence of non-endometrioid component, or specific concurrent gene mutations in the tumor. For comparison, nuclear localization of ß-catenin was more diffuse in desmoid fibromatosis, a tumor also associated with CTNNB1 mutation. Thus, nuclear localization of ß-catenin assessed by immunohistochemistry does not detect all endometrial cancers with CTNNB1 gene mutation. The extent of nuclear localization may be tumor type dependent. For endometrial cancer, immunohistochemistry could be an initial screen, with CTNNB1 sequencing employed when nuclear localization of ß-catenin is absent.

Radical Hysterectomy and Age: Outcomes Comparison Based on a Minimally Invasive vs an Open Approach.

STUDY OBJECTIVE: To compare outcomes of radical hysterectomy (RH) across age groups based on surgical approach: minimally invasive surgery (MIS) vs laparotomy (LP). DESIGN: Cross-sectional retrospective review (Canadian Task Force classification II-2). SETTING: Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas M.D. Anderson Cancer Center. PATIENTS: Patients with early-stage cervical cancer who underwent RH at a tertiary cancer center between 1990 and 2013. INTERVENTIONS: Patients were stratified by age group (<50, 50-59, and ≥60 years) and by surgical approach (minimally invasive surgery [MIS] vs laparotomy [LP]). MEASUREMENTS AND MAIN RESULTS: Patients with early-stage cervical cancer who underwent RH were retrospectively reviewed to obtain demographic data, surgical data, and clinical outcomes. We used the Fisher exact, Wilcoxon rank-sum, and Cochran-Mantel-Haenszel tests to compare categorical and continuous variables stratified by surgical approach and age group. A total of 548 patients were evaluated, including 427 (77.9%) who underwent LP (age <50, 84.3%; 50-59, 11.2%; ≥60, 4.5%) and 121 (22.1%) who underwent MIS (age <50, 71.9%; 50-59, 17.3%; ≥60, 10.8%). In the MIS group, 71 patients (58.7%) underwent laparoscopy and 50 (41.3%) underwent robotic surgery. Patients in the MIS group were significantly older and heavier than those in the LP group. The operative time was significantly longer in the MIS group. There was no between-group difference in intraoperative complications in any of the 3 age groups. LP patients had more infectious complications (respiratory, systemic, and wound) than MIS patients in the <50-year age group (53.3% vs 21.8%). The difference between the LP and MIS groups with respect to the postoperative noninfectious complication rate was greatest in the ≥60-year age group (p = .0324). CONCLUSION: The between-group difference in postoperative noninfectious complication rate in the oldest age group was twice that in either of the other 2 age groups (p = .0324), even though the MIS patients were older, heavier, and had a longer operative time compared with the LP patients.