Secondary Cytoreduction and Carboplatin Hyperthermic Intraperitoneal Chemotherapy for Platinum-Sensitive Recurrent Ovarian Cancer: An MSK Team Ovary Phase II Study.

PURPOSE: The purpose of this phase II study was to evaluate hyperthermic intraperitoneal chemotherapy (HIPEC) with carboplatin for recurrent ovarian cancer during secondary cytoreductive surgery. MATERIALS AND METHODS: Patients were intraoperatively randomly assigned to carboplatin HIPEC (800 mg/m2 for 90 minutes) or no HIPEC, followed by five or six cycles of postoperative IV carboplatin-based chemotherapy, respectively. Based on a binomial single-stage pick-the-winner design, an arm was considered winner if ≥ 17 of 49 patients were without disease progression at 24 months post-surgery. Secondary objectives included postoperative toxicity and HIPEC pharmacokinetics. RESULTS: Of 98 patients, 49 (50%) received HIPEC. Complete gross resection was achieved in 82% of the HIPEC patients and 94% of the standard-arm patients. Bowel resection was performed in 37% of patients in the HIPEC arm compared with 65% in the standard (P = .008). There was no perioperative mortality and no difference in use of ostomies, length of stay, or postoperative toxicity. At 24 months, eight patients (16.3%; 1-sided 90% CI, 9.7 to 100) were without progression or death in the HIPEC arm and 12 (24.5%; 1-sided 90% CI, 16.5 to 100) in the standard arm. With a medium follow-up of 39.5 months, 82 patients progressed and 37 died. The median progression-free survival in the HIPEC and standard arms were 12.3 and 15.7 months, respectively (hazard ratio, 1.54; 95% CI, 1 to 2.37; P = .05). There was no significant difference in median overall survival (52.5 v 59.7 months, respectively; hazard ratio, 1.39; 95% CI, 0.73 to 2.67; P = .31). These analyses were exploratory. CONCLUSION: HIPEC with carboplatin was well tolerated but did not result in superior clinical outcomes. This study does not support the use of HIPEC with carboplatin during secondary cytoreductive surgery for platinum-sensitive recurrent ovarian cancer.

The 'Eat Well @ IGA' healthy supermarket randomised controlled trial: process evaluation.

BACKGROUND: Successful implementation and long-term maintenance of healthy supermarkets initiatives are crucial to achieving potential population health benefits. Understanding barriers and enablers of implementation of real-world trials will enhance wide-scale implementation. This process evaluation of a healthy supermarket intervention sought to describe (i) customer, retailer and stakeholder perspectives on the intervention; (ii) intervention implementation; and (iii) implementation barriers and enablers. METHODS: Eat Well @ IGA was a 12-month randomised controlled trial conducted in 11 Independent Grocers of Australia (IGA) chain supermarkets in regional Victoria, Australia (5 intervention and 6 wait-listed control stores). Intervention components included trolley and basket signage, local area and in-store promotion, and shelf tags highlighting the healthiest packaged foods. A sequential mixed-methods process evaluation was undertaken. Customer exit surveys investigated demographics, and intervention recall and perceptions. Logistic mixed-models estimated associations between customer responses and demographics, with store as random effect. Supermarket staff surveys investigated staff demographics, interactions with customers, and intervention component feedback. Semi-structured stakeholder interviews with local government, retail and academic partners explored intervention perceptions, and factors which enabled or inhibited implementation, maintenance and scalability. Interviews were inductively coded to identify key themes. RESULTS: Of 500 customers surveyed, 33%[95%CI:23,44] recalled the Eat Well @ IGA brand and 97%[95%CI:93,99] agreed that IGA should continue its efforts to encourage healthy eating. The 82 staff surveyed demonstrated very favourable intervention perceptions. Themes from 19 interviews included that business models favour sales of unhealthy foods, and that stakeholder collaboration was crucial to intervention design and implementation. Staff surveys and interviews highlighted the need to minimise staff time for project maintenance and to regularly refresh intervention materials to increase and maintain salience among customers. CONCLUSIONS: This process evaluation found that interventions to promote healthy diets in supermarkets can be perceived as beneficial by retailers, customers, and government partners provided that barriers including staff time and intervention salience are addressed. Collaborative partnerships in intervention design and implementation, including retailers, governments, and academics, show potential for encouraging long-term sustainability of interventions. TRIAL REGISTRATION: ISRCTN, ISRCTN37395231 Registered 4 May 2017.

Prophylactic Negative Pressure Wound Therapy After Laparotomy for Gynecologic Surgery: A Randomized Controlled Trial.

OBJECTIVE: To estimate the effectiveness of prophylactic negative pressure wound therapy in patients undergoing laparotomy for gynecologic surgery. METHODS: We conducted a randomized controlled trial. Eligible, consenting patients, regardless of body mass index (BMI), who were undergoing laparotomy for presumed gynecologic malignancy were randomly allocated to standard gauze or negative pressure wound therapy. Patients with BMIs of 40 or greater and benign disease also were eligible. Randomization, stratified by BMI, occurred after skin closure. The primary outcome was wound complication within 30 (±5) days of surgery. A sample size of 343 per group (N=686) was planned. RESULTS: From March 1, 2016, to August 20, 2019, we identified 663 potential patients; 289 were randomized to negative pressure wound therapy (254 evaluable participants) and 294 to standard gauze (251 evaluable participants), for a total of 505 evaluable patients. The median age of the entire cohort was 61 years (range 20-87). Four hundred ninety-five patients (98%) underwent laparotomy for malignancy. The trial was eventually stopped for futility after an interim analysis of 444 patients. The rate of wound complications was 17.3% in the negative pressure wound therapy (NPWT) group and 16.3% in the gauze group, absolute risk difference 1% (90% CI -4.5 to 6.5%; P=.77). Adjusted odds ratio controlling for estimated blood loss and diabetes was 0.99 (90% CI 0.62-1.60). Skin blistering occurred in 33 patients (13%) in the NPWT group and in three patients (1.2%) in the gauze group (P<.001). CONCLUSION: Negative pressure wound therapy after laparotomy for gynecologic surgery did not lower the wound complication rate but did increase skin blistering. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02682316. FUNDING SOURCE: The protocol was supported in part by KCI/Acelity.

Exploring barriers to meeting recommendations for fruit and vegetable intake among adults in regional areas: A mixed-methods analysis of variations across socio-demographics.

Fruit and vegetable consumption is low compared to recommendations worldwide. Few studies have investigated intakes of fruit and vegetables and barriers to meeting recommendations in a mixed-method design. Moreover, there is a need to better understand differences in these barriers by population subgroups. This study aimed to examine fruit and vegetable intake and barriers to meeting recommendations and differences by sex, age and socio-economic groups. Data on adults from the cross-sectional Greater Bendigo Active Living Census 2014 were used. Participants self-reported intake of fruit and vegetables and completed an open-ended question on barriers to meeting recommended intakes. Logistic regression analyses were used to examine odds of meeting recommended intakes. Leximancer was used for thematic analyses of barriers. A total of 13,788 individuals (54% female, 52.1 (SD 17.7) years) were included in the quantitative analyses. Qualitative data were available for 5649 of these individuals. Only seven percent of participants met recommended intakes for fruit and vegetables. Barriers were lack of time, that guidelines were perceived as unachievable, the wide variety of other foods available and the high cost and limited availability of fresh fruit and vegetables. The most relevant barriers by subgroups were: taste (12%) and lack of appetite (18%) for males and females, respectively; lack of time (26-28%) and lack of appetite (70%) for young to middle aged adults and older adults, respectively and cost (35%) and availability of fresh fruits and vegetables (22%) for rural and disadvantaged groups. Findings have implications for the design of healthy eating strategies, which may benefit from being tailored to key population groups.

Utility of tumor marker HE4 to predict depth of myometrial invasion in endometrioid adenocarcinoma of the uterus.

OBJECTIVE: The purpose of this pilot study was to determine whether the biomarker human epididymis protein 4 (HE4) correlates with depth of myometrial invasion, histologic grade, lymph vascular space invasion, positive cytologic washings, and nodal metastases in patients with endometrioid adenocarcinoma of the uterus. METHODS: This was a prospective, observational study in women with biopsy-proven endometrioid adenocarcinoma. Concentrations of HE4 were assessed before surgery, and all surgical specimens were reviewed by dedicated gynecologic pathologists. RESULTS: Included were a total of 96 women with endometrioid adenocarcinomas of the uterus, most (77%) with stage I disease. Levels of serum HE4 greater than 70 pM displayed a sensitivity of 94% and a negative predictive value of 97% in identifying stage IA (<50% myometrial invasion) versus stage IB (≥ 50% myometrial invasion) tumors and a sensitivity of 82% and negative predictive value of 82% versus all more advanced tumors. CONCLUSIONS: Human epididymis protein 4 may be a useful marker preoperatively in the clinical decision process for determining the need for lymph node dissection in women with endometrioid endometrial cancer.

Comparison of a novel multiple marker assay vs the Risk of Malignancy Index for the prediction of epithelial ovarian cancer in patients with a pelvic mass.

OBJECTIVE: We sought to compare the Risk of Malignancy Index (RMI) to the Risk of Ovarian Malignancy Algorithm (ROMA) to predict epithelial ovarian cancer (EOC) in women with a pelvic mass. STUDY DESIGN: In all, 457 women with imaging results from ultrasound, computed tomography, magnetic resonance imaging, and serum HE4 and CA125 determined prior to surgery for pelvic mass were evaluable. RMI values were determined using CA125, imaging score, and menopausal status. ROMA values were determined using HE4, CA125, and menopausal status. RESULTS: At a set specificity of 75%, ROMA had a sensitivity of 94.3% and RMI had a sensitivity of 84.6% for distinguishing benign status from EOC (P = .0029). In patients with stage I and II disease, ROMA achieved a sensitivity of 85.3% compared with 64.7% for RMI (P < .0001). CONCLUSION: The dual marker algorithm utilizing HE4 and CA125 to calculate a ROMA value achieves a significantly higher sensitivity for identifying women with EOC than does RMI.

A novel multiple marker bioassay utilizing HE4 and CA125 for the prediction of ovarian cancer in patients with a pelvic mass.

INTRODUCTION: Patients diagnosed with epithelial ovarian cancer (EOC) have improved outcomes when cared for at centers experienced in the management of EOC. The objective of this trial was to validate a predictive model to assess the risk for EOC in women with a pelvic mass. METHODS: Women diagnosed with a pelvic mass and scheduled to have surgery were enrolled on a multicenter prospective study. Preoperative serum levels of HE4 and CA125 were measured. Separate logistic regression algorithms for premenopausal and postmenopausal women were utilized to categorize patients into low and high risk groups for EOC. RESULTS: Twelve sites enrolled 531 evaluable patients with 352 benign tumors, 129 EOC, 22 LMP tumors, 6 non EOC and 22 non ovarian cancers. The postmenopausal group contained 150 benign cases of which 112 were classified as low risk giving a specificity of 75.0% (95% CI 66.9-81.4), and 111 EOC and 6 LMP tumors of which 108 were classified as high risk giving a sensitivity of 92.3% (95% CI=85.9-96.4). The premenopausal group had 202 benign cases of which 151 were classified as low risk providing a specificity of 74.8% (95% CI=68.2-80.6), and 18 EOC and 16 LMP tumors of which 26 were classified as high risk, providing a sensitivity of 76.5% (95% CI=58.8-89.3). CONCLUSION: An algorithm utilizing HE4 and CA125 successfully classified patients into high and low risk groups with 93.8% of EOC correctly classified as high risk. This model can be used to effectively triage patients to centers of excellence.

Utility of a novel serum tumor biomarker HE4 in patients with endometrioid adenocarcinoma of the uterus.

OBJECTIVE: Tumor markers with increased sensitivity and specificity for endometrial cancer are needed to help monitor response to therapy and to detect recurrent disease. Currently, the tumor maker CA125 is utilized in this role with limited value. The objectives of this study were to examine the levels of several novel tumor markers HE4, SMRP, CA72.4 and CA125 as potential markers in patients diagnosed with endometrioid adenocarcinoma of the uterus. METHODS: Pre-operative serum samples from surgically staged patients with endometrioid adenocarcinoma of the uterus were analyzed for levels of HE4, SMRP, CA72-4 and CA125. Control samples were obtained from healthy postmenopausal women. Logistic regression models and receiver operating characteristic (ROC) curves were constructed for each tumor marker and for all combinations, with cross-validation analyses to obtain average sensitivities at set specificities of 90%, 95%, and 98%. RESULTS: Serum samples from 156 healthy subjects and 171 patients with endometrial cancer (122 stage I, 17 stage II, 26 stage III, and 6 stage IV) were analyzed. At a 95% specificity, the sensitivities for differentiating between healthy subjects and all stages of cancer were 45.5% for HE4 and 24.6% for CA125. For stage I disease, HE4 yielded a 17.1% improvement in sensitivity compared with CA125. CONCLUSION: HE4 is elevated in all stages of endometrial can100cer and is more sensitive in early-stage endometrial cancer compared to CA125. Further investigation of HE4 as a marker for early detection of recurrent endometrial cancer and monitoring response to therapy is warranted.

Isolated sentinel lymph node dissection with conservative management in patients with squamous cell carcinoma of the vulva: a prospective trial.

OBJECTIVES: Sentinel lymph node (SLN) dissections have a high sensitivity and negative predictive value for the detection of metastatic disease. The objective of this study was to examine the inguinal recurrence rate along with complication rates for patients undergoing inguinal SLN dissection alone for vulvar carcinoma. METHODS: An IRB approved prospective study enrolled patients with biopsy proven squamous cell carcinoma of the vulva. Peritumoral injection of Tc-99 sulfur colloid and methylene blue dye was used to identify SLNs intraoperatively. Patients with SLNs negative for metastatic disease were followed clinically. Patients with metastasis detected in a SLN subsequently underwent a full groin node dissection followed by standard treatment protocols. RESULTS: Thirty-six patients were enrolled onto study with 35 undergoing a SLN dissection. All SNL dissections were successful with a mean of 2 SLN obtained per groin. There were 24 patients with stage I disease, 8 stage II, 3 stage III and 1 stage IV. A total of 56 SLN dissections were performed with 4 patients found to have inguinal metastasis by SLN dissection. There were 31 patients with a total of 46 SLN dissections found to be negative for metastatic disease. The median follow-up has been 29 months (range 8 to 51) with 2 groin recurrences for a groin recurrence rate of 4.3% and a recurrence rate per patient of 6.4%. There have been no reports of groin breakdown, extremity cellulitis or lymphedema. CONCLUSIONS: The recurrence rate for patients undergoing inguinal sentinel node dissection alone is low. These patients did not experience any complications as seen with complete groin node dissections. Sentinel lymph node dissection should be considered as an option for evaluation of inguinal nodes for metastatic disease.

The use of multiple novel tumor biomarkers for the detection of ovarian carcinoma in patients with a pelvic mass.

OBJECTIVES: The CA125 tumor marker is used to help predict the presence of ovarian cancer in patients with an adnexal mass. Because elevated CA125 levels occur in many benign gynecologic conditions, we set out to identify other novel biomarkers that would increase the sensitivity and specificity of CA125. METHODS: Serum and urine samples were obtained preoperatively from women undergoing surgery for an adnexal mass. The samples were analyzed for levels of CA125, SMRP, HE4, CA72-4, activin, inhibin, osteopontin, epidermal growth factor (EGFR), and ERBB2 (Her2) and were compared to final pathology results. Logistic regression models were estimated for all markers and combinations, with cross-validation analysis performed to obtain the sensitivities at set specificities of 90%, 95%, and 98%. RESULTS: Two hundred and fifty-nine patients with adnexal masses were enrolled. Of these, 233 patients were eligible for analysis with 67 invasive epithelial ovarian cancers and 166 benign ovarian neoplasms. Mean values for all marker levels except Her2 differed significantly between patients with benign masses and cancer. As a single marker, HE4 had the highest sensitivity at 72.9% (specificity 95%). Comparatively, combined CA125 and HE4 yielded the highest sensitivity at 76.4% (specificity 95%), with additional markers adding minimally to the sensitivity of this combination. HE4 was the best single marker for Stage I disease, with no increase in sensitivity when combined with CA125 or any other marker. CONCLUSIONS: As a single tumor marker, HE4 had the highest sensitivity for detecting ovarian cancer, especially Stage I disease. Combined CA125 and HE4 is a more accurate predictor of malignancy than either alone.