Anna C. Snavely

Rates of Renal Toxicity in Cancer Patients Receiving Cisplatin With and Without Mannitol

Background: Cisplatin is a widely used antineoplastic. One of the major complications of cisplatin use is dose-limiting nephrotoxicity. There are many strategies to prevent this toxicity, including the use of mannitol as a nephroprotectant in combination with hydration. Objective: We aimed to evaluate the rates of cisplatin-induced nephrotoxicity in cancer patients receiving single-agent cisplatin with and without mannitol. Methods: This single-center retrospective analysis was a quasi experiment created by the national mannitol shortage. Data were collected on adult cancer patients receiving single-agent cisplatin as an outpatient from January 2011 to September 2012. The primary outcome was acute kidney injury (AKI). Results: We evaluated 143 patients who received single-agent cisplatin; 97.2% of patients had head and neck cancer as their primary malignancy. Patients who did not receive mannitol were more likely to develop nephrotoxicity: odds ratio [OR] = 2.646 (95% CI = 1.008, 6.944; P = 0.048). Patients who received the 100 mg/m2 dosing and patients who had a history of hypertension also had a higher likelihood of developing nephrotoxicity: OR = 11.494 (95% CI = 4.149, 32.258; P < 0.0001) and OR = 3.219 (95% CI = 1.228, 8.439; P = 0.017), respectively. Conclusions: When limited quantities of mannitol are available, it should preferentially be given to patients at particularly high risk of nephrotoxicity. Our analysis suggests that those patients receiving the dosing schedule of 100 mg/m2 cisplatin every 3 weeks and those with hypertension are at the greatest risk of nephrotoxicity and would benefit from the addition of mannitol.

Preoperative quality of life and surgical outcomes in gynecologic oncology patients: A new predictor of operative risk?

OBJECTIVE Quality of life (QoL) for women with gynecologic malignancies is predictive of chemotherapy related toxicity and overall survival but has not been studied in relation to surgical outcomes and hospital readmissions. Our goal was to evaluate the association between baseline, pre-operative QoL measures and 30-day post-operative morbidity and health resource utilization by gynecologic oncology patients. METHODS We analyzed prospectively collected survey data from an institution-wide cohort study. Patients were enrolled from 8/2012 to 6/2013 and medical record data was abstracted (demographics, comorbid conditions, and operative outcomes). Responses from several validated health-related QoL instruments were collected. Bivariate tests and multivariable linear and logistic regression models were used to evaluate factors associated with QoL scores. RESULTS Of 182 women with suspected gynecologic malignancies, 152 (84%) were surveyed pre-operatively and 148 (81%) underwent surgery. Uterine (94; 63.5%), ovarian (26; 17.5%), cervical (15; 10%), vulvar/vaginal (8; 5.4%), and other (5; 3.4%) cancers were represented. There were 37 (25%) cases of postoperative morbidity (PM), 18 (12%) unplanned ER visits, 9(6%) unplanned clinic visits, and 17 (11.5%) hospital readmissions (HR) within 30days of surgery. On adjusted analysis, lower functional well-being scores resulted in increased odds of PM (OR 1.07, 95%CI 1.01-.1.21) and HR (OR 1.11, 95%CI 1.03-1.19). A subjective global assessment score was also strongly associated with HR (OR 1.89, 95%CI 1.14, 3.16). CONCLUSION Lower pre-operative QoL scores are significantly associated with post-operative morbidity and hospital readmission in gynecologic cancer patients. This relationship may be a novel indicator of operative risk.

The Incidence of Catheter-Associated Venous Thrombosis in Noncritically Ill Children

OBJECTIVE Previous studies estimated the incidence of catheter-associated venous thrombosis to be between 2% and 81%. Our goals were to define the incidence rate of catheter-related thrombosis in a hospitalized, noncritically ill, pediatric population and to determine modifiable factors that alter the risk of thrombosis. METHODS A retrospective cohort study was performed at the North Carolina Childrens Hospital from 2009 to 2012. Chart review was performed with extraction of patient characteristics and line-related variables. Presence of symptomatic catheter-associated venous thrombosis was the primary outcome. Bivariable analysis and multivariable logistic regression were used to explore associations between line-related variables and thrombosis. RESULTS A total of 1135 lines were placed in 815 patients for 118,023 catheter-days. Thirty-six were complicated by venous thrombosis (3.2%) yielding a rate of 0.3 events per 1000 catheter-days. In multivariable analysis, increasing age (odds ratio [OR] 1.08, 95% confidence interval [CI] 1.03-1.13; P=.002), renal dialysis (OR 3.2, 95% CI 1.09-9.66; P=.035), and a diagnosis of inflammatory bowel disease or short bowel syndrome (OR 4.3, 95% CI 1.2-15.0; P=.02) were associated with increased risk of thrombosis. Modifiable risk factors, such as line site, size, and lumens, were not significantly associated with thrombosis. No thromboembolic events were observed. CONCLUSIONS We observed a lower incidence rate of catheter-associated venous thrombosis than in most previous reports. No modifiable characteristics altered the risk of thrombosis. Additional investigation of measures to prevent thrombosis is warranted in higher-risk populations, such as patients undergoing dialysis or patients with inflammatory bowel disease.

Obesity is associated with worse quality of life in women with gynecologic malignancies: An opportunity to improve patient‐centered outcomes

The objective of the current study was to evaluate the effect of obesity on pretreatment quality of life (QoL) in gynecologic oncology patients.

Chemotherapy and Stem Cell Transplantation Increase p16INK4a Expression, a Biomarker of T-cell Aging

The expression of markers of cellular senescence increases exponentially in multiple tissues with aging. Age-related physiological changes may contribute to adverse outcomes in cancer survivors. To investigate the impact of high dose chemotherapy and stem cell transplantation on senescence markers in vivo, we collected blood and clinical data from a cohort of 63 patients undergoing hematopoietic cell transplantation. The expression of p16INK4a, a well-established senescence marker, was determined in T-cells before and 6 months after transplant. RNA sequencing was performed on paired samples from 8 patients pre- and post-cancer therapy. In patients undergoing allogeneic transplant, higher pre-transplant p16INK4a expression was associated with a greater number of prior cycles of chemotherapy received (p = 0.003), prior autologous transplantation (p = 0.01) and prior exposure to alkylating agents (p = 0.01). Transplantation was associated with a marked increase in p16INK4a expression 6 months following transplantation. Patients receiving autologous transplant experienced a larger increase in p16INK4a expression (3.1-fold increase, p = 0.002) than allogeneic transplant recipients (1.9-fold increase, p = 0.0004). RNA sequencing of T-cells pre- and post- autologous transplant or cytotoxic chemotherapy demonstrated increased expression of transcripts associated with cellular senescence and physiological aging. Cytotoxic chemotherapy, especially alkylating agents, and stem cell transplantation strongly accelerate expression of a biomarker of molecular aging in T-cells.

Use of mobile device technology to continuously collect patient-reported symptoms during radiation therapy for head and neck cancer: A prospective feasibility study

Purpose Accurate assessment of toxicity allows for timely delivery of supportive measures during radiation therapy for head and neck cancer. The current paradigm requires weekly evaluation of patients by a provider. The purpose of this study is to evaluate the feasibility of monitoring patient reported symptoms via mobile devices. Methods and materials We developed a mobile application for patients to report symptoms in 5 domains using validated questions. Patients were asked to report symptoms using a mobile device once daily during treatment or more often as needed. Clinicians reviewed patient-reported symptoms during weekly symptom management visits and patients completed surveys regarding perceptions of the utility of the mobile application. The primary outcome measure was patient compliance with mobile device reporting. Compliance is defined as number of days with a symptom report divided by number of days on study. Results There were 921 symptom reports collected from 22 patients during treatment. Median reporting compliance was 71% (interquartile range, 45%-80%). Median number of reports submitted per patient was 34 (interquartile range, 21-53). Median number of reports submitted by patients per week was similar throughout radiation therapy and there was significant reporting during nonclinic hours. Patients reported high satisfaction with the use of mobile devices to report symptoms. Conclusions A substantial percentage of patients used mobile devices to continuously report symptoms throughout a course of radiation therapy for head and neck cancer. Future studies should evaluate the impact of mobile device symptom reporting on improving patient outcomes.

The health-related quality of life journey of gynecologic oncology surgical patients: Implications for the incorporation of patient-reported outcomes into surgical quality metrics

OBJECTIVE To report the changes in patient-reported quality of life for women undergoing gynecologic oncology surgeries. METHODS In a prospective cohort study from 10/2013-10/2014, women were enrolled pre-operatively and completed comprehensive interviews at baseline, 1, 3, and 6months post-operatively. Measures included the disease-specific Functional Assessment of Cancer Therapy-General (FACT-GP), general Patient Reported Outcome Measure Information System (PROMIS) global health and validated measures of anxiety and depression. Bivariate statistics were used to analyze demographic groups and changes in mean scores over time. RESULTS Of 231 patients completing baseline interviews, 185 (80%) completed 1-month, 170 (74%) 3-month, and 174 (75%) 6-month interviews. Minimally invasive (n=115, 63%) and laparotomy (n=60, 32%) procedures were performed. Functional wellbeing (20 → 17.6, p<0.0001) decreased at 1-month, and recovered by 3 and 6months. Emotional wellbeing increased (16.3 → 20.1, p<0.0001) and anxiety decreased (54.2 → 49.0, p<0.0001) at 1-month, and were stable at 3 and 6months. Physical wellbeing scales were not sensitive to surgery. These patterns were consistent across procedure type, cancer diagnosis, and adjuvant therapy administration. In an exploratory analysis of the interaction of QOL and quality, patients with increased postoperative healthcare resource use were noted to have higher baseline levels of anxiety. CONCLUSIONS For women undergoing gynecologic oncology procedures, temporary declines in functional wellbeing are balanced by improvements in emotional wellbeing and decreased anxiety symptoms after surgery. Not all commonly used QOL surveys are sensitive to changes during the perioperative period and may not be suitable for use in surgical quality metrics.

A latent variable transformation model approach for exploring dysphagia

Multiple outcomes are often collected in applications where the quantity of interest cannot be measured directly or is difficult or expensive to measure. In a head and neck cancer study conducted at Dana-Farber Cancer Institute, the investigators wanted to determine the effect of clinical and treatment factors on unobservable dysphagia through collected multiple outcomes of mixed types. Latent variable models are commonly adopted in this setting. These models stipulate that multiple collected outcomes are conditionally independent given the latent factor. Mixed types of outcomes (e.g., continuous vs. ordinal) and censored outcomes present statistical challenges, however, as a natural analog of the multivariate normal distribution does not exist for mixed data. Recently, Lin et al. proposed a semiparametric latent variable transformation model for mixed outcome data; however, it may not readily accommodate event time outcomes where censoring is present. In this paper, we extend the work of Lin et al. by proposing both semiparametric and parametric latent variable models that allow for the estimation of the latent factor in the presence of measurable outcomes of mixed types, including censored outcomes. Both approaches allow for a direct estimate of the treatment (or other covariate) effect on the unobserved latent variable, greatly enhancing the interpretability of the models. The semiparametric approach has the added advantage of allowing the relationship between the measurable outcomes and latent variables to be unspecified, rendering more robust inference. The parametric and semiparametric models can also be used together, providing a comprehensive modeling strategy for complicated latent variable problems.

Intraoperative Handoffs and Postoperative Complications Among Patients Undergoing Gynecologic Oncology Operations.

Abstract: There is evidence that systems-based factors influence surgical outcomes of intraoperative and postoperative morbidity. The goal of this study was to provide an exploratory analysis of systems-based variables and their associations with surgical outcomes in gynecologic oncology patients. We merged electronic records from operating room software with billing claims from major surgeries performed from 2011 to 2013, at a tertiary care academic medical center. Univariate and bivariate analyses were performed to evaluate the relationship between baseline demographic and clinical covariates (age, comorbidity, procedure type, and surgeon volume), the main exposure variables (case start time, case order, and personnel handoffs), and the primary outcome of 30-day postoperative complications. Multiple logistic regression models were created to analyze the contributing effect of each systemic variable on postoperative complications. The overall rate of postoperative complications among patients was 31.4% (n = 182). Although traditional risk factors of comorbidity, procedure type, and case length were the strongest primary drivers of complication risk, there was a significant relationship between handoffs among surgical scrub technicians and postoperative complications (odds ratio: 2.12; 95% CI: 1.00–4.47). As a novel finding in surgical quality and safety research, this supports greater efforts into integrating key staffing information into studies of systemic variables and surgical outcomes.

Prior breast cancer and tamoxifen exposure does not influence outcomes in women with uterine papillary serous carcinoma

OBJECTIVES To evaluate progression-free survival (PFS) and overall survival (OS) outcomes in women diagnosed with uterine papillary serous carcinoma (UPSC) who have had (UPSCBR+) or have not had (UPSCBR-) an antecedent history of breast cancer and to correlate their outcomes to prior tamoxifen exposure. METHODS Data were collected for women diagnosed with UPSC at two academic institutions between January 1997 and July 2012. Patient demographics, tumor histology, stage, and treatments were recorded. Patients were divided into two groups: those with and without a personal history of breast cancer. Within the UPSCBR+ cohort, we identified those with a history of tamoxifen use. Cox regression modeling was used to explore associations between selected covariates of interest and the time-to-event outcomes of PFS and OS. RESULTS Of 323 patients with UPSC, 46 (14%) were UPSCBR+. Of these, 15 (33%) had a history of tamoxifen use. UPSCBR+ patients were older than UPSCBR- (median years, 72 vs. 68, p=0.004). UPSCBR+ women showed no significant difference in PFS or OS compared to UPSCBR- (p=0.64 and p=0.73 respectively), even after controlling for age (p=0.15 and p=0.48 respectively). Within the UPSCBR+ cohort, there was no difference in PFS or OS with or without tamoxifen exposure (p=0.98 and p=0.94 respectively). CONCLUSIONS There was no difference in PFS or OS between the UPSCBR+ and UPSCBR- cohorts. We did not demonstrate significant OS or PFS differences in women who took tamoxifen prior to their endometrial cancer diagnosis. These findings have implications for counseling, and should be encouraging to women who are facing their second cancer diagnosis.