A UVR-sensor wearable device intervention to reduce sun exposure in melanoma survivors: Results from a randomized controlled trial.

BACKGROUND: Melanoma survivors are at increased risk of developing a second primary melanoma; however, some report sub-optimal sun behaviors and sunburns. We tested the effectiveness of a wearable device with ultraviolet radiation (UVR)-sensing technology to improve sun behaviors and reduce sunburns in cutaneous melanoma survivors. MATERIALS AND METHODS: We conducted a randomized controlled trial using Shade 2, a commercially available wrist device that measures UVR. The intervention group received the device and mobile application notifications about their exposure and prompts to use sunscreen. The control group received the device and a separate research mobile application without information about their exposure or notifications. Participants wore the device for 12 weeks and self-reported sun behaviors before, during, and after the intervention. The primary outcome was a composite score of sun protection behaviors at week 12. RESULTS: 386 participants were randomized (186 control, 182 intervention). Most were female and 5+ years past their first melanoma diagnosis. The average age was 56 years. Most (93%) completed the study, though 40% experienced device issues. No meaningful differences were observed in self-reported sun protection behaviors at week 12 (controls 3.0±0.5 vs. intervention 2.9±0.5, p = 0.06), any sunburn during the intervention period (controls 14.4% vs. intervention 12.7%, p = 0.75), or average daily objective UVR exposure (controls median 87 vs. intervention 83 J/m2, p = 0.43). CONCLUSION: Wearing a device that measured and alerted melanoma survivors to UVR exposure did not result in different sun behaviors, exposure, or sunburns relative to controls. The technology needs refinement before further attempts to assess the effectiveness of self-monitoring UVR exposure. CLINICAL TRIALS REGISTRATION: NCT03927742.

Development of a multiplexed giant magnetoresistive biosensor array prototype to quantify ovarian cancer biomarkers.

In this work, we developed benchtop and handheld Giant Magnetoresistive (GMR) biosensing systems that serve as platforms for detecting a wide variety of protein biomarkers for human diseases. System development included spintronic and nanomagnetic materials, biomolecular chemistry, electronic circuitry, analog and digital signal processing, firmware programming, user interface programming on both PC and Android smartphone, communications over both USB and Bluetooth, and mechanical integration. In this work, we demonstrated the benchtop GMR biosensing system in the context of ovarian cancer assay development. The prototype system delivered the required performance in terms of high-sensitivity multiplex assays in a portable format with enough flexibility to serve as a platform for ovarian cancer and many other diseases. We achieved multiplex detection of cancer antigen 125 (CA125 II), human epididymis protein 4 (HE4), and interleukin 6 (IL6), with limits of detection (LOD) as low as 3.7 U/mL, 7.4 pg/mL, and 7.4 pg/mL, respectively.

Arterial elasticity as a risk factor for early cardiovascular disease among testicular cancer survivors treated with platinum-based chemotherapy: a cross-sectional pilot study.

PURPOSE: Testicular cancer survivors who have received platinum-based chemotherapy are at risk for premature cardiovascular disease. The etiology of this risk is not well understood. This pilot study explores the impact of platinum-based chemotherapy on endothelial function. METHODS: Testicular cancer survivors <30 years old at the time of diagnosis who received platinum-based chemotherapy between 2002 and 2012, as well as 17 similarly aged male controls, were identified. Consented subjects underwent vascular assessment using the HDI/PulseWave CR-2000 Cardiovascular Profiling System and the Endo-PAT2000 system. Biomarkers and functional test markers were compared among cases, controls, and a group of historical controls using two sided two-sampled t-tests and Wilcoxon rank-sum tests. RESULTS: Thirteen survivors with a median age of 30.2 years and body mass index of 27.3 were enrolled, along with 17 healthy controls with a median age of 27.1 years and body mass index of 24.8. Median time from chemotherapy was 4.7 (range: 0.8-14) years. There was no statistical difference in reactive hyperemia peripheral arterial tonometry ratio between cases and controls (p = 0.574). There was no statistical difference in small or large artery elasticity between cases and controls (p = 0.086) or between cases and historical controls (p = 0.729). There was also no statistical difference in the blood levels of circulating endothelial cells, von Willebrand factor, and vascular cell adhesion molecules. There was a trend toward increased metabolic syndrome in cases (15%) as compared to recruited controls (6%), though this difference was not statistically significant (p = 0.565). CONCLUSION: Testicular cancer survivors have no clinically significant difference in endothelial function compared to controls 4 years after the completion of chemotherapy. Further research is needed to explore the secondary modifiable causes that may contribute to the risk of premature cardiovascular disease.

A qualitative study of barriers to genetic counseling and potential for mobile technology education among women with ovarian cancer.

BACKGROUND: National guidelines recommend genetic counseling for all ovarian cancer patients because up to 20% of ovarian cancers are thought to be due to hereditary cancer syndromes and effective cancer screening and prevention options exist for at-risk family members. Despite these recommendations, uptake of genetic counselling and testing is low. The goal of this study was to identify barriers to and motivators for receipt of genetic counseling along with preferences regarding potential use of a mobile application to promote genetic counseling. METHODS: Three focus groups were conducted including 14 women with a diagnosis of epithelial ovarian, primary peritoneal or fallopian tube cancer. Topics included understanding of genetic counseling, perceived pros and cons, preferences for receiving health information, and familiarity with mobile phone technology. Transcripts were analyzed using standard procedures of qualitative thematic text analysis and descriptive coding techniques. RESULTS: Six major themes regarding barriers to and motivators of genetic counseling and use of mobile technology in promoting genetic counseling emerged: (1) need for information, (2) relevance, (3) emotional concerns, (4) family concerns, (5) practical concerns, and (6) mobile application considerations. CONCLUSIONS: These data reiterate previously reported barriers to genetic counseling as observed in other populations. Participants were supportive of the use of mobile technology for promoting uptake of genetic counseling.

Chemotherapy-Induced Tunneling Nanotubes Mediate Intercellular Drug Efflux in Pancreatic Cancer.

Intercellular communication plays a critical role in the ever-evolving landscape of invasive cancers. Recent studies have elucidated the potential role of tunneling nanotubes (TNTs) in this function. TNTs are long, filamentous, actin-based cell protrusions that mediate direct cell-to-cell communication between malignant cells. In this study, we investigated the formation of TNTs in response to variable concentrations of the chemotherapeutic drug doxorubicin, which is used extensively in the treatment of cancer patients. Doxorubicin stimulated an increased formation of TNTs in pancreatic cancer cells, and this occurred in a dose-dependent fashion. Furthermore, TNTs facilitated the intercellular redistribution of this drug between connected cells in both pancreatic and ovarian cancer systems in vitro. To provide supportive evidence for the relevance of TNTs in pancreatic cancer in vivo, we performed multiphoton fluorescence microscopy and imaged TNTs in tumor specimens resected from three human patients with pancreatic adenocarcinoma, and one with neuroendocrine carcinoma. In sum, TNT formation was upregulated in aggressive forms of pancreatic carcinoma, was further stimulated after chemotherapy exposure, and acted as a novel method for drug efflux. These findings implicate TNTs as a potential novel mechanism of drug resistance in chemorefractory forms of cancer.

Effect of intra-operative glove changing during cesarean section on post-operative complications: a randomized controlled trial.

PURPOSE: To compare the rates of wound-related complications among women undergoing a cesarean section when the surgical team used intra-operative glove changing versus usual care. METHODS: All women undergoing a cesarean section at a single, county hospital were randomized to usual care or intra-operative glove changing prior to abdominal closure. Participants were randomized at the time of decision for cesarean section; surgeons were not blinded to the randomization arm. The primary outcome was any wound-related complication, including wound hematoma, seroma, skin separation of at least 1 cm, wound infection, or other incisional abnormality requiring treatment within 8 weeks of surgery. To detect a reduction in the primary outcome from 17% in the control group to 9% in the intervention group with 80% power, a total of 554 women (277 per group) were required. Secondary outcomes included other infectious complications including endometritis and other superficial or deep soft tissue infections. RESULTS: From August 2015 to November 2016, 277 women were randomized to usual care and 276 women were randomized to intra-operative glove changing. The two groups were well balanced in terms of demographic data, comorbid conditions and surgical characteristics. Intra-operative glove changing led to a significant decrease in composite wound complications from 13.6% in the control group to 6.4% in the intervention group (p = 0.008). CONCLUSION: Intra-operative glove changing prior to abdominal closure during cesarean section significantly reduced the incidence of post-operative wound complications.

A Cross-Sectional Review of Cervical Cancer Messages on Twitter During Cervical Cancer Awareness Month.

OBJECTIVES: The objectives of this study were to quantify personal stories about cervical cancer and to determine the proportion and sentiment (positive vs negative) of messages ("tweets") that discussed cervical cancer prevention strategies on Twitter. METHODS: This study was a cross-sectional Twitter review of English-language top tweets about cervical cancer during the Cervical Cancer Awareness month, January 2016. Theme categories were identified, and tweets were independently coded by 2 reviewers; discrepancies in coding were resolved by a third reviewer. Descriptive statistical analyses were performed. RESULTS: During January 2016, approximately 348 top tweets about cervical cancer were identified. Professional health organizations produced 20.7% of tweets, and individuals identifying themselves as health-care professionals contributed an additional 4%. In addition to the tweet, 45.1% attached a photo or video; 54.6% included links to a larger article. Only 11.2% of tweets included personal stories from cervical cancer patients. Among the top tweets, 70.3% were focused on prevention through screening and/or HPV vaccination, with 97.4% recommending such practices. A substantial proportion of the Twitter traffic (24.7%) referenced the #SmearForSmear campaign by the patient-advocate organization Jo's Cervical Cancer Trust, based in the United Kingdom. CONCLUSIONS: Analysis of top tweets during the cervical cancer awareness month showed that, although personal stories about cervical cancer were rare, cervical cancer prevention was a popular topic during the cervical cancer awareness month. This was largely driven by a picture-based twitter campaign from a single advocacy organization.

Prophylactic Negative Pressure Wound Therapy in Obese Patients Following Cesarean Delivery.

OBJECTIVE: Negative pressure therapy (NPT) offers the potential to reduce infection in obese patients. The goal of this study was to explore the association between NPT use and infection after cesarean delivery among obese women. METHODS: We initiated a hospital protocol wherein women with a body mass index (BMI) of 40 kg/m2 or greater who delivered after January 1, 2011 were to receive NPT following cesarean section. A retrospective comparison of surgical site infection (SSI) in women receiving the intervention to a similar group with a BMI of 40 kg/m2 or greater, a historical control group of women who delivered before January 1, 2011. Incidence of SSI was compared between time periods using logistic regression models. RESULTS: A total of 233 patients in the preintervention (control) group and 234 patients in the intervention group were included in the analysis. In the control group, 23 (9.9%) developed SSI, compared with 13 (5.6%) in the intervention group. After adjustment for potential confounding factors, women in the postintervention period experienced a statistically significant reduction in SSI rates (adjusted odds ratio =0.45, 95% CI = 0.22-0.95); P = .04). CONCLUSION: Implementation of a hospital protocol of NPT following cesarean delivery in obese women resulted in reduced incidence of postoperative SSI. This study suggests that using NPT after cesarean delivery in women with a BMI ≥40 kg/m2 is an efficacious method to reduce incidence of postoperative wound infections.

Patterns of postpartum contraceptive use among Somali immigrant women living in Minnesota.

BACKGROUND: The postpartum period is a crucial time to provide family planning counseling and can decrease incidence of adverse reproductive outcomes. The purpose of this study was to characterize patterns of postpartum contraception and to investigate long acting reversible contraceptive (LARC) use among Somali women living in a metropolitan area of Minnesota in an effort to provide better family planning and reproductive health counseling in this growing immigrant population. METHODS: A retrospective chart review was conducted of Somali women who delivered between January 1, 2011 and December 31, 2014. Information was collected regarding family planning counseling provided and contraceptive methods chosen at the postpartum clinic visit. RESULTS: Of the 747 Somali women who delivered during this time period, 56.4% had no postpartum follow up visit. At the postpartum visit, 88.3% of women received family planning counseling and 80.8% chose a contraceptive method with the remainder declining. The intrauterine device (IUD) was the most popular contraceptive method, chosen by 39.7% of women. Other than parity, no statistically significant differences were observed between women who chose LARC versus other contraceptive methods. Of the women that chose a LARC, 39.4% had it placed at the time of their postpartum visit; immediate placement was statistically significantly more likely with more recent delivery, lower BMI and obstetrician as the provider type. CONCLUSIONS: The IUD was the most popular method of postpartum contraception. There was a trend toward increase in LARC use with increasing parity. Same-day LARC placement was uncommon, but should be encouraged in this population given high loss to follow up rate.

Sun Exposure and Protection Behaviors among Long-term Melanoma Survivors and Population Controls.

Introduction: Melanoma is considered a generally preventable cancer, with excessive ultraviolet radiation (UVR) exposure being a strong causal factor. UVR exposure following a melanoma diagnosis can be modified to reduce risk of second primary melanomas. The goal of this study was to compare measures of UVR exposure and protection behaviors between long-term melanoma survivors and controls.Methods: Participants from a previously conducted case-control study were recruited for a cross-sectional survey. Melanoma cases were 25 to 59 years old at diagnosis; controls were age and sex matched. Participants were asked about UVR exposure and protection measures used in the past year, and comparisons between melanoma survivors and controls were conducted using logistic regression models, adjusting for potential confounders.Results: A total of 724 (62.0%) long-term melanoma survivors and 660 (59.9%) controls completed the follow-up survey. Melanoma survivors were significantly less likely to report high sun exposure on a typical weekday [OR, 0.72 (0.55-0.94)], sunburns [OR, 0.40 (0.30-0.53)], or indoor tanning [OR, 0.20 (0.09-0.44)] than controls; however, high sun exposure on a typical weekend day was similar. Report of optimal sun protection behaviors was higher in melanoma survivors compared with controls. However, a few melanoma survivors reported indoor tanning, 10% reported intentionally seeking sun to tan, and 20% reported sunburns.Conclusions: Although long-term melanoma survivors reported healthier UVR exposure and protection behaviors compared with controls, a sizeable proportion still reported elevated sun exposure, sunburns, and suboptimal UVR protection behaviors.Impact: Opportunities remain for improving sun protection to reduce future melanoma risk among melanoma survivors. Cancer Epidemiol Biomarkers Prev; 26(4); 607-13. ©2017 AACR.

Comparison of quality of life among long-term melanoma survivors and non-melanoma controls: a cross-sectional study.

PURPOSE: Little is known about specific concerns facing long-term melanoma survivors. The goal of this study was to compare quality of life (QOL) and mental health between long-term melanoma survivors and population controls. METHODS: Participants from a previously conducted case-control study of risk factors for melanoma were recruited for a cross-sectional survey. Generic QOL and emotional health were measured using the SF-36 and Hospital Anxiety and Depression Scale questionnaires. A total of 724 melanoma survivors and 660 controls participated. Most melanoma survivors had stage I disease (85.6%); mean time from diagnosis was 9.6 ± 1.0 years. Comparisons of QOL measures between melanoma survivors and controls were conducted using regression models, adjusting for potential confounders. RESULTS: Melanoma survivors, compared to controls, reported statistically significant but only slightly higher physical functioning and bodily pain QOL subscale scores than controls and otherwise similar QOL as measured by the remaining six SF-36 subscale scores. Prevalence of anxiety (18.1% vs. 19.3%, adjusted OR = 1.00 (0.74, 1.36); p = 1.00) and depression (7.2% vs. 9.8%, adjusted OR = 0.74 (0.48, 1.16); p = 1.00) were similar between melanoma survivors and controls. CONCLUSION: Long-term early stage melanoma survivors report similar general QOL and mental health compared to population controls. Further research is needed to identify concerns more specific to melanoma.

UNC-45A is required for neurite extension via controlling NMII activation.

UNC-45A is a highly conserved member of the UNC-45/CRO1/She4p family of proteins, which act as chaperones for conventional and nonconventional myosins. NMII mediates contractility and actin-based motility, which are fundamental for proper growth cone motility and neurite extension. The presence and role of UNC-45A in neuronal differentiation have been largely unknown. Here we demonstrate that UNC-45A is a novel growth cone--localized, NMII-associated component of the multiprotein complex regulating growth cone dynamics. We show that UNC-45A is dispensable for neuron survival but required for neurite elongation. Mechanistically, loss of UNC-45A results in increased levels of NMII activation. Collectively our results provide novel insights into the molecular mechanisms of neurite growth and define UNC-45A as a novel and master regulator of NMII-mediated cellular processes in neurons.

Enhanced Recovery Program and Length of Stay After Laparotomy on a Gynecologic Oncology Service: A Randomized Controlled Trial.

OBJECTIVE: To estimate whether a rapid recovery program would reduce length of stay among patients undergoing laparotomy on a gynecologic oncology service. METHODS: We conducted a prospective, randomized, controlled trial comparing an enhanced recovery after surgery protocol with routine postoperative care among women undergoing laparotomy on the gynecologic oncology service. Protocol elements included: preoperative counseling, regional anesthesia, intraoperative fluid restriction, and early postoperative ambulation and feeding. A sample size of 50 per group (N=100) was planned to achieve 80% power to detect a two-day difference in our primary outcome, length of hospital stay; secondary outcomes included: total daily narcotics used, time to postoperative milestones, and complications. RESULTS: A total of 112 women were enrolled between 2013 and 2015. Nine patients did not undergo laparotomy and were excluded, leaving 52 and 51 patients in the control and intervention groups, respectively. There was no difference in length of stay between the two groups (median 3.0 in both groups; P=.36). Enhanced recovery after surgery patients used less narcotics on day 0 (10.0 compared with 5.5 morphine equivalents in the control and intervention arms, respectively, P=.09) and day 2 (10.0 compared with 7.5 morphine equivalents, respectively; P=.05); however, there was no statistically significant difference between groups in any of the secondary outcomes. Post hoc analysis based on actual anesthesia received also failed to demonstrate a difference in time to discharge. CONCLUSION: When compared with usual care, introducing a formal enhanced recovery after surgery protocol did not significantly reduce length of stay. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT01705288.

Evaluation of the American College of Surgeons National Surgical Quality Improvement Program Surgical Risk Calculator in Gynecologic Oncology Patients Undergoing Minimally Invasive Surgery.

STUDY OBJECTIVE: To evaluate the ability of the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) surgical risk calculator to predict discharge to postacute care and perioperative complications in gynecologic oncology patients undergoing minimally invasive surgery (MIS). DESIGN: A retrospective chart review (Canadian Task Force classification II-1). SETTING: A university hospital. PATIENTS: All patients undergoing MIS on the gynecologic oncology service from January 1, 2009, to December 30, 2013. INTERVENTIONS: Surgical procedures were reviewed, and appropriate Common Procedural Terminology codes were assigned. Twenty-one preoperative risk factors were abstracted from the chart and entered into the ACS NSQIP surgical risk calculator. The predicted risk of discharge to postacute care and 8 additional postoperative complications were calculated and recorded. Actual postoperative complications were abstracted from the medical record. The association between the calculated risk and the actual outcome was determined using logistic regression. The ability of the calculator to accurately predict a particular event was assessed using the c-statistic and Brier score. MEASUREMENTS AND MAIN RESULTS: Of the 876 patients reviewed, a majority underwent hysterectomy (71.6%), with almost half of those patients undergoing additional cancer staging procedures (34.8%). Although the calculator was a poor predictor of postoperative complications, it was a strong predictor for discharge to postacute care (c-statistic = 0.91, Brier score = 0.02) with an odds ratio of 2.31 (95% confidence interval, 1.65-3.25; p < .0001). CONCLUSION: The ACS NSQIP surgical risk calculator does not accurately predict postoperative complications or length of stay in gynecologic oncology patients undergoing MIS. Although it was a strong predictor of need for discharge to postacute care, it vastly overestimated the number of patients requiring this service. Therefore, the calculator's risk score for discharge to postacute care may be considered during preoperative counseling but should not be a predictor of whether or not the patient should proceed with surgery.

The DNA cytosine deaminase APOBEC3B promotes tamoxifen resistance in ER-positive breast cancer.

Breast tumors often display extreme genetic heterogeneity characterized by hundreds of gross chromosomal aberrations and tens of thousands of somatic mutations. Tumor evolution is thought to be ongoing and driven by multiple mutagenic processes. A major outstanding question is whether primary tumors have preexisting mutations for therapy resistance or whether additional DNA damage and mutagenesis are necessary. Drug resistance is a key measure of tumor evolvability. If a resistance mutation preexists at the time of primary tumor presentation, then the intended therapy is likely to fail. However, if resistance does not preexist, then ongoing mutational processes still have the potential to undermine therapeutic efficacy. The antiviral enzyme APOBEC3B (apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3B) preferentially deaminates DNA C-to-U, which results in signature C-to-T and C-to-G mutations commonly observed in breast tumors. We use clinical data and xenograft experiments to ask whether APOBEC3B contributes to ongoing breast tumor evolution and resistance to the selective estrogen receptor modulator, tamoxifen. First, APOBEC3B levels in primary estrogen receptor-positive (ER+) breast tumors inversely correlate with the clinical benefit of tamoxifen in the treatment of metastatic ER+ disease. Second, APOBEC3B depletion in an ER+ breast cancer cell line results in prolonged tamoxifen responses in murine xenograft experiments. Third, APOBEC3B overexpression accelerates the development of tamoxifen resistance in murine xenograft experiments by a mechanism that requires the enzyme's catalytic activity. These studies combine to indicate that APOBEC3B promotes drug resistance in breast cancer and that inhibiting APOBEC3B-dependent tumor evolvability may be an effective strategy to improve efficacies of targeted cancer therapies.

Gender differences in snus versus nicotine gum for cigarette avoidance among a sample of US smokers.

INTRODUCTION: Women are more susceptible to the harmful effects of cigarette smoking. Thus, identifying effective harm reduction approaches for women is necessary. The goal of this project was to examine gender differences in response to snus versus nicotine gum for cigarette avoidance, as a means of harm reduction. METHODS: Participants were randomly assigned to use snus or nicotine gum as a method to avoid cigarette smoking. Participants attended clinic visits to receive study product, as well as provide biological samples to assess smoking avoidance and biomarkers and report on use of study product and cigarettes. A secondary analysis comparing men and women by randomization to study product was conducted. RESULTS: Participants (n=391; 47% women) were randomized into the snus group (n=196; 45% women) and the gum group (n=195; 49% women). Men used more snus whereas women used more gum (p=0.02). During treatment, men in the snus group had higher total nicotine equivalent values whereas women did not vary by group (p=0.03). Overall, fewer men in the snus group completely avoided cigarettes compared to men in the gum group (e.g., continuous abstinence at Week 12: odds ratio=0.43, 95% confidence interval=0.20-0.93). Among women, there were no differences by randomization in cigarette avoidance. CONCLUSIONS: Despite a number of gender differences in response to snus versus nicotine gum, these data suggest that snus may not be an optimal harm reduction approach for either gender.

Temozolomide treatment of pituitary carcinomas and atypical adenomas: systematic review of case reports.

BACKGROUND: Pituitary carcinomas (PC) and atypical pituitary adenomas (APA) are rare variants of pituitary tumors for which no evidence-based treatment currently exists. We sought to determine whether temozolomide represents an effective chemotherapeutic option for patients with PC and APA. METHODS: A systematic review was performed using all published cases of PC and APA treated with temozolomide, and for which information on treatment regimen, clinical response, and survival could be identified. The primary goal of this analysis was to describe overall survival and progression-free survival among PC and APA patients after temozolomide treatment. Secondary goals included assessment of response rate and biomarkers of response. RESULTS: We identified 57 cases and obtained follow-up data on 54 patients (31 APA and 23 PC) for analysis. Estimates of 5-year progression-free survival and overall survival were 21.9% and 57.4% for patients with APA and 36.1% and 56.2% for patients with PC. Among those who responded to temozolomide, overall survival was marginally statistically significantly greater for patients on long-term temozolomide therapy compared with those who were not (5-year overall survival 91.7% vs 54.1%, P = .08); Progression-free survival results were similar but not statistically significant. The objective response rate was 48.4% for patients with APA and 65.2% for patients with PC. Stable disease occurred in 29% of APA and 17.4% of PC patients. Neither histology nor expression of Ki-67 correlated with response; however, negative O6-methylguanine-DNA methyltransferase staining was strongly related to response to temozolomide in patients with APA (P < .001). CONCLUSIONS: Temozolomide is an effective treatment of both PC and APA, and long-term treatment can be considered for particularly aggressive cases.

Long term follow-up of a phase II trial of multimodal therapy given in a "sandwich" method for stage III, IV, and recurrent endometrial cancer.

BACKGROUND: Our objective was to determine if previously reported overall survival (OS) and progression-free survival (PFS) rates are maintained long term following multimodal therapy for advanced and recurrent endometrial cancer and to assess the lymphedema rates associated with this therapy. METHODS: Women with advanced-stage or recurrent endometrial cancer were recruited between 9/2004 and 6/2009 to our previously published Phase II trial. Patients received intravenous docetaxel (75 mg/m2) and carboplatin (AUC = 6) every 3 weeks for 3 cycles before and after radiation therapy. Patient outcomes were updated in July 2014. Data abstracted included presence of lymphedema, disease progression, and death. OS and PFS estimates at 5 years were calculated using Kaplan-Meier methods. RESULTS: Of the 41 patients enrolled, 10 (24 %) had stage IIIA and 21 (51 %) had stage IIIC disease; 32 (78 %) had endometrioid histology; and 35 (85 %) completed the protocol. With a median follow-up of 5 years, 15 of 41 patients have died. The Kaplan-Meier estimate and 95 % CI for OS at 5 years was 70 % (53-82 %). Excluding the two patients with recurrent disease at enrollment, 15 of 39 patients progressed or died during follow-up. The Kaplan-Meier estimate and 95 % CI for PFS at 5 years was 66 % (48-78 %). Fifteen patients (37 %) had medical record documentation of lymphedema following treatment. CONCLUSIONS: After additional follow-up, OS and PFS estimates remain high and in-field recurrences low following "sandwich" therapy. The "sandwich" method remains efficacious for women with stage III-IV or recurrent endometrial cancer.

Quantitative comparison and reproducibility of pathologist scoring and digital image analysis of estrogen receptor ß2 immunohistochemistry in prostate cancer.

BACKGROUND: Digital image analysis offers advantages over traditional pathologist visual scoring of immunohistochemistry, although few studies examining the correlation and reproducibility of these methods have been performed in prostate cancer. We evaluated the correlation between digital image analysis (continuous variable data) and pathologist visual scoring (quasi-continuous variable data), reproducibility of each method, and association of digital image analysis methods with outcomes using prostate cancer tissue microarrays (TMAs) stained for estrogen receptor-ß2 (ERß2). METHODS: Prostate cancer TMAs were digitized and evaluated by pathologist visual scoring versus digital image analysis for ERß2 staining within tumor epithelium. Two independent analysis runs were performed to evaluate reproducibility. Image analysis data were evaluated for associations with recurrence-free survival and disease specific survival following radical prostatectomy. RESULTS: We observed weak/moderate Spearman correlation between digital image analysis and pathologist visual scores of tumor nuclei (Analysis Run A: 0.42, Analysis Run B: 0.41), and moderate/strong correlation between digital image analysis and pathologist visual scores of tumor cytoplasm (Analysis Run A: 0.70, Analysis Run B: 0.69). For the reproducibility analysis, there was high Spearman correlation between pathologist visual scores generated for individual TMA spots across Analysis Runs A and B (Nuclei: 0.84, Cytoplasm: 0.83), and very high correlation between digital image analysis for individual TMA spots across Analysis Runs A and B (Nuclei: 0.99, Cytoplasm: 0.99). Further, ERß2 staining was significantly associated with increased risk of prostate cancer-specific mortality (PCSM) when quantified by cytoplasmic digital image analysis (HR 2.16, 95 % CI 1.02-4.57, p = 0.045), nuclear image analysis (HR 2.67, 95 % CI 1.20-5.96, p = 0.016), and total malignant epithelial area analysis (HR 5.10, 95 % CI 1.70-15.34, p = 0.004). After adjusting for clinicopathologic factors, only total malignant epithelial area ERß2 staining was significantly associated with PCSM (HR 4.08, 95 % CI 1.37-12.15, p = 0.012). CONCLUSIONS: Digital methods of immunohistochemical quantification are more reproducible than pathologist visual scoring in prostate cancer, suggesting that digital methods are preferable and especially warranted for studies involving large sample sizes.

A model for patient-direct screening and referral for familial cancer risk.

Patients at increased familial risk of cancer are sub-optimally identified and referred for genetic counseling. We describe a systematic model for information collection, screening and referral for hereditary cancer risk. Individuals from three different clinical and research populations were screened for hereditary cancer risk using a two-tier process: a 7-item screener followed by review of family history by a genetic counselor and application of published criteria. A total of 869 subjects participated in the study; 769 in this high risk population had increased familial cancer risk based on the screening questionnaire. Of these eligible participants, 500 (65.0 %) provided family histories and 332 (66.4 %) of these were found to be at high risk of a hereditary cancer syndrome, 102 (20.4 %) at moderate familial cancer risk, and 66 (13.2 %) at average risk. Three months following receipt of the risk result letter, nearly all respondents found the process at least somewhat helpful (98.4 %). All participants identified as high-risk were mailed a letter recommending genetic counseling and were provided appointment tools. After 1 year, only 13 (7.3 %) of 179 high risk respondents reported pursuit of recommended genetic counseling. Participants were willing to provide family history information for the purposes of risk assessment; however, few patients pursued recommended genetic services. This suggests that cancer family history registries are feasible and viable but that further research is needed to increase the uptake of genetic counseling.