Bryan Fellman

Illness Uncertainty and Quality of Life of Patients with Small Renal Tumors Undergoing Watchful Waiting: A 2-year Prospective Study

BACKGROUND Few studies have examined factors associated with the quality of life (QOL) of patients with renal tumors. Illness uncertainty may influence QOL. OBJECTIVE To prospectively examine the influence of uncertainty on general and cancer-specific QOL and distress in patients undergoing watchful waiting (WW) for a renal mass. DESIGN, SETTING, AND PARTICIPANTS In 2006-2010, 264 patients were enrolled in a prospective WW registry. The decision for WW was based on patient, tumor, and renal function characteristics at the discretion of the urologist and medical oncologist in the context of the physician-patient interaction. Participants had suspected clinical stage T1-T2 disease, were aged ≥ 18 yr, and spoke and read English. The first 100 patients enrolled in the registry participated in this study. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Patients completed questionnaires on demographics, illness uncertainty (Mishel Uncertainty in Illness Scale), general QOL (Medical Outcomes Study 36-item short-form survey), cancer-specific QOL (Cancer Rehabilitation Evaluation System-Short Form), and distress (Impact of Events Scale) at enrollment and at 6, 12, and 24 mo. Age, gender, ethnicity, tumor size, estimated glomerular filtration rate, comorbidities, and assessment time point were controlled for in the models. RESULTS AND LIMITATIONS Among the sample, 27 patients had biopsies, and 17 patients had proven renal cell carcinoma. Growth rate was an average of 0.17 cm/yr (standard deviation: 0.35). Mean age was 72.5 yr, 55% of the patients were male, and 84% of the patients were Caucasian. Greater illness uncertainty was associated with poorer general QOL scores in the physical domain (p=0.008); worse cancer-related QOL in physical (p=0.001), psychosocial (p<0.001), and medical (p=0.034) domains; and higher distress (p<0.001). CONCLUSIONS This study is among the first to prospectively examine the QOL of patients with renal tumors undergoing WW and the psychosocial factors that influence QOL. Illness uncertainty predicted general QOL, cancer-specific QOL, and distress. These factors could be targeted in psychosocial interventions to improve the QOL of patients on WW.

Consequences of universal MSI/IHC in screening ENDOMETRIAL cancer patients for lynch syndrome

OBJECTIVE Determine factors impacting the uptake of genetic counseling and results of genetic testing following universal tumor testing for Lynch syndrome in patients with endometrial cancer. METHODS The study population consisted of two unselected cohorts of endometrial cancer patients, 408 identified retrospectively and 206 identified prospectively. Immunohistochemistry for mismatch repair protein expression and/or microsatellite instability analysis was performed on these tumors. MLH1 methylation analysis was performed on tumors with loss of MLH1 protein. Tumor studies were considered suggestive of Lynch Syndrome if they showed immunohistochemical loss of MSH2, MSH6 or PMS2, loss of MLH1 without MLH1 promoter methylation, and/or microsatellite instability. Participants with suggestive tumor studies were contacted and offered genetic counseling and testing. RESULTS In the retrospective cohort, 11% had tumor studies suggestive of Lynch syndrome, and 42% was seen for genetic counseling. A germline mutation was detected in 40%, and one had a variant of uncertain significance. In the prospective cohort, 8.7% of patients had tumor testing suggestive of Lynch syndrome; 72% were seen for genetic counseling. Germline mutations were found in 40%, and one had a variant of uncertain significance. Common challenges included timing of re-contact, age, perceived lack of relevance, inability to travel and limited insurance coverage. CONCLUSIONS There are several barriers to genetic counseling and testing follow-up after universal tumor testing, and uninformative genetic test results present a management challenge. It is important to consider these limitations when implementing an approach to screening endometrial cancer patients for Lynch syndrome.

Overall survival after pelvic exenteration for gynecologic malignancy

BACKGROUND Five-Year survival after pelvic exenteration for gynecologic malignancies has been reported as high as 60%. The objective of this study was to determine overall survival (OS) after pelvic exenteration and evaluate factors impacting outcome. METHODS A retrospective review of all women who underwent pelvic exenteration at our institution between February 1993 and December 2010 was performed. OS was defined as time from exenteration to date of death or last contact. Survival analysis was performed using the Kaplan Meyer method. Multivariate analysis was performed to determine the impact of clinical and pathologic factors on survival outcomes. RESULTS One hundred sixty patients with gynecologic malignancy underwent pelvic exenteration. Five-year recurrence free survival (RFS) was 33% (95%CI 0.25-0.40). Factors which negatively impacted RFS included shorter treatment-free interval (p=.050), vulvar primary (p=.032), positive margins (p<.001), lymphovascular space invasion (LVSI, p<.001), positive lymph nodes (p<.001) and perineural invasion (p=0.030). In multivariate analysis, positive margins (p=.040), positive nodes (p<.001) and lymphovascular space invasion (LVSI, p=.003) retained a significant impact on RFS. Five-year OS was 40% (95% CI 0.32-0.48). Factors which negatively impacted OS included vulvar primary (p=.04), positive margins (p<.001), LVSI (p<.001), positive lymph nodes (p<.001) and perineural invasion (p=.008). In multivariate analysis, positive nodes (p=.001) and LVSI (p=.001) retained a significant impact on OS. CONCLUSION Five-year OS after pelvic exenteration was 40%. Survival outcomes have not significantly improved despite improvements in technique and patient selection. Multiple non-modifiable factors at the time of exenteration are associated with poor survival.

Evaluation of Clinical Criteria for the Identification of Lynch Syndrome among Unselected Patients with Endometrial Cancer

Clinical criteria, primarily young age of cancer onset and family history of signature cancers, have been developed to identify individuals at elevated risk for Lynch syndrome with the goals of early identification and cancer prevention. In 2007, the Society of Gynecologic Oncology (SGO)–codified criteria for women presenting with gynecologic cancers. These criteria have not been validated in a population-based setting. For 412 unselected endometrial cancers, immunohistochemical expression of DNA mismatch repair proteins and MLH1 methylation were assessed to classify tumors as sporadic or probable Lynch syndrome (PLS). In this cohort, 10.5% of patients were designated as PLS based on tumor testing. The sensitivity and specificity of the SGO criteria to identify these same cases were 32.6% [95% confidence interval (CI), 19.2–48.5] and 77% (95% CI, 72.7–81.8), respectively. With the exception of tumor location in the lower uterine segment, multivariate analysis of clinical features, family history, and pathologic variables failed to identify significant differences between the sporadic and PLS groups. A simplified cost-effectiveness analysis demonstrated that the SGO clinical criteria and universal tissue testing strategies had comparable costs per patient with PLS identified. In conclusion, the SGO criteria successfully identify PLS cases among women with endometrial cancer who are young or have significant family history of signature tumors. However, a larger proportion of patients with PLS who are older and have less significant family history are not detected by this screening strategy. Universal tissue testing may be necessary to capture more individuals at risk for having Lynch syndrome. Cancer Prev Res; 7(7); 686–97. ©2014 AACR.

Attitudes toward molecular testing for personalized cancer therapy

This study assessed attitudes of breast cancer patients toward molecular testing for personalized therapy and research.

Comprehensive Assessment of Quality of Life and Psychosocial Adjustment in Patients With Renal Tumors Undergoing Open, Laparoscopic and Nephron Sparing Surgery

PURPOSE We prospectively evaluated the general and cancer specific quality of life, and psychosocial adjustment of patients with a renal mass treated with radical vs partial nephrectomy via a laparoscopic or an open approach. MATERIALS AND METHODS A total of 172 patients with renal tumors completed questionnaires before surgery, and 3 weeks, and 2, 3, 6 and 12 months postoperatively. We assessed general quality of life using SF-36™ and cancer specific quality of life using the Cancer Rehabilitation Evaluation System-Short Form, in addition to intrusive thoughts, avoidance behaviors and fear of recurrence. We used mixed model regression analysis to compare these measures across surgery types during the study course, adjusted for tumor size, histology, stage and renal function. RESULTS The SF-36 physical component score differed significantly by surgery type with time (p = 0.04). Patients treated with laparoscopy improved by month 2 while those treated with open surgery had poorer quality of life until month 3. Better cancer specific quality of life was reported in patients who underwent radical vs partial nephrectomy. Age also had a significant effect on outcomes. CONCLUSIONS We report one of the most comprehensive patient reported prospective quality of life studies in patients with renal cell carcinoma. There were significant differences in quality of life and psychosocial adjustment outcomes during 1 year among patients treated with 1 of 4 commonly accepted surgical renal procedures. These outcomes must be evaluated in the context of tumor characteristics, cancer specific outcomes and renal function. These quality of life issues may be important to consider when choosing surgical procedures for patients with renal tumors.

Priorities for oncology nursing research: The 2013 national survey

PURPOSE/OBJECTIVES To advance the goals of evidence-based care and prioritize the knowledge generation that addresses contemporary challenges in oncology nursing. Results are used to inform the development of the Oncology Nursing Society (ONS) Research Agenda and by the ONS Foundation to develop strategic research initiatives. DESIGN Descriptive, cross-sectional survey. SETTING Web-based survey. SAMPLE 8,554 ONS members from all levels of education. All doctorally prepared members were invited to participate. A random stratified sample was obtained from the remainder of the membership. METHODS The ONS Research Priorities Survey project team created the survey and analyzed and interpreted the results. Members received an email invitation and follow-up reminders for survey completion. MAIN RESEARCH VARIABLES Oncology nursing research and evidence-based practice topic questions. FINDINGS The response rate was 11%, which is comparable to previous surveys. Topics ranked included descriptive research on patient adherence; intervention studies to optimize adherence, achieve concordance with cancer screening guidelines in minority populations, manage neurologic and cardiovascular late effects, and manage symptoms and symptom clusters; and studies to identify optimal delivery models for survivorship care. These findings have direct implications for translating existing evidence into practice and underscore the need for intervention research focused on improving patient-centered outcomes. CONCLUSIONS Results provide a broad assessment of member views regarding oncology research priorities. Given the response rate, additional strategies to encourage member participation will be considered. IMPLICATIONS FOR NURSING The results, together with the updates of the ONS Research Agenda, can guide ONS and ONS Foundation research and evidence-based practice initiatives.

Postoperative outcomes after continent versus incontinent urinary diversion at the time of pelvic exenteration for gynecologic malignancies

OBJECTIVE To compare outcomes of patients undergoing continent or incontinent urinary diversion after pelvic exenteration for gynecologic malignancies. METHODS Data on patients who underwent pelvic exenteration for gynecologic malignancies at The University of Texas MD Anderson Cancer Center between January 1993 and December 2010 were collected. A multivariate logistic regression model was used and statistical significance was P<0.05. RESULTS A total of 133 patients were included in this study. The mean age at exenteration was 47.6 (range, 30-73) years in the continent urinary diversion group and 57.2 (range, 27-86) years in the incontinent urinary diversion group (P<0.0001). Forty-six patients (34.6%) had continent urinary diversion, and 87 patients (65.4%) had incontinent urinary diversion. The rates of postoperative complications in patients with continent and incontinent urinary diversion, respectively, were as follows: pyelonephritis, 32.6% versus 37.9% (P=0.58); urinary stone formation, 34.8% versus 2.3% (P<0.001); renal insufficiency, 4.4% versus 14.9% (P=0.09); urostomy stricture, 13.0% versus 1.2% (P=0.007); ureteral (anastomotic) leak, 4.4% versus 6.9% (P=0.71); ureteral (anastomotic) stricture, 13.0% versus 23% (P=0.25); fistula formation, 21.7% versus 19.5% (P=0.82); and reoperation because of complications of urinary diversion, 6.5% versus 2.3% (P=0.34). Among patients with continent urinary diversion, the incidence of incontinence was 28.3%, and 15.2% had difficulty with self-catheterization. CONCLUSION There were no differences in postoperative complications between patients with continent and incontinent conduits except that stone formation was more common in patients with continent conduits.

Development and Cross-Validation of the In-Hospital Mortality Prediction in Advanced Cancer Patients Score: A Preliminary Study

PURPOSE Acute palliative care units (APCUs) provide intensive symptom support and transition of care for advanced cancer patients. Better understanding of the predictors of in-hospital mortality is needed to facilitate program planning and patient care. In this prospective study, we identified predictors of APCU mortality, and developed a four-item In-hospital Mortality Prediction in Advanced Cancer Patients (IMPACT) predictive model. METHODS Between April and July 2010, we documented baseline demographics, the Edmonton Symptom Assessment Scale (ESAS), 80 clinical signs including known prognostic factors, and 26 acute complications on admission in consecutive APCU patients. Multivariate logistic regression analysis was used to identify factors for inclusion in a nomogram, which was cross-validated with bootstrap analysis. RESULTS Among 151 consecutive patients, the median age was 58, 13 (9%) had hematologic malignancies, and 52 (34%) died in the hospital. In multivariate analysis, factors associated with in-hospital mortality were advanced education (odds ration [OR]=11.8, p=0.002), hematologic malignancies (OR=8.6, p=0.02), delirium (OR=4.3, p=0.02), and high ESAS global distress score (OR=20.8, p=0.01). In a nomogram based on these four factors, total scores of 6, 10, 14, 17, and 21 corresponded to a risk of death of 10%, 25%, 50%, 75%, and 90%, respectively. The model has 92% sensitivity and 88% specificity for predicting patients at low/high risk of dying in the hospital, and a receiver-operator characteristic curve concordance index of 83%. CONCLUSIONS Higher education was associated with increased utilization of the interdisciplinary palliative care unit until at the end of life. Patients with higher symptom burden, delirium, and hematologic malignancies were also more likely to require APCU care until death.

Cross-talk between EphA2 and BRaf/CRaf is a key determinant of response to dasatinib

Purpose: EphA2 is an attractive therapeutic target because of its diverse roles in cancer growth and progression. Dasatinib is a multikinase inhibitor that targets EphA2 and other kinases. However, reliable predictive markers and a better understanding of the mechanisms of response to this agent are needed. Experimental design: The effects of dasatinib on human uterine cancer cell lines were examined using a series of in vitro experiments, including MTT, Western blot analysis, and plasmid transfection. In vivo, an orthotopic mouse model of uterine cancer was utilized to identify the biologic effects of dasatinib. Molecular markers for response prediction and the mechanisms relevant to response to dasatinib were identified by using reverse phase protein array (RPPA), immunoprecipitation, and double immunofluorescence staining. Results: We show that high levels of CAV-1, EphA2 phosphorylation at S897, and the status of PTEN are key determinants of dasatinib response in uterine carcinoma. A set of markers essential for dasatinib response was also identified and includes CRaf, pCRafS338, pMAPKT202/Y204 (mitogen-activated protein kinase [MAPK] pathway), pS6S240/244, p70S6kT389 (mTOR pathway), and pAKTS473. A novel mechanism for response was discovered whereby high expression level of CAV-1 at the plasma membrane disrupts the BRaf/CRaf heterodimer and thus inhibits the activation of MAPK pathway during dasatinib treatment. Conclusions: Our in vitro and in vivo results provide a new understanding of EphA2 targeting by dasatinib and identify key predictors of therapeutic response. These findings have implications for ongoing dasatinib-based clinical trials. Clin Cancer Res; 20(7); 1846–55. ©2014 AACR.