Self-management intervention improves patient adherence to swallowing exercises during radiation for head and neck cancer.

BACKGROUND: While preventive swallowing exercises reduce the risk of radiation-associated dysphagia in patients with head and neck cancer, strategies are needed to improve patient adherence. METHODS: Before radiation, all participants were taught preventive swallowing exercises and randomized to either an adherence intervention or enhanced usual care. During radiation, all participants met twice with a speech pathologist for swallowing assessment and reinforcement of exercises. Intervention participants met weekly with a counselor in-person or by phone. At 6-week post-radiation follow-up, all participants completed a follow-up assessment of self-reported adherence, which was then corroborated with medical record documentation. RESULTS: Newly diagnosed pharyngeal and laryngeal cancer patients without distant metastases were randomized (n = 265; 135 to intervention, and 130 to usual care). Intervention participants were more likely to adhere to exercises during radiation compared to the control group (p < 0.0001). CONCLUSION: The weekly in-person adherence intervention program significantly increased patient's adherence to preventive swallowing exercises during radiation.

Plasmonic nano-aperture label-free imaging of single small extracellular vesicles for cancer detection.

BACKGROUND: Small extracellular vesicle (sEV) analysis can potentially improve cancer detection and diagnostics. However, this potential has been constrained by insufficient sensitivity, dynamic range, and the need for complex labeling. METHODS: In this study, we demonstrate the combination of PANORAMA and fluorescence imaging for single sEV analysis. The co-acquisition of PANORAMA and fluorescence images enables label-free visualization, enumeration, size determination, and enables detection of cargo microRNAs (miRs). RESULTS: An increased sEV count is observed in human plasma samples from patients with cancer, regardless of cancer type. The cargo miR-21 provides molecular specificity within the same sEV population at the single unit level, which pinpoints the sEVs subset of cancer origin. Using cancer cells-implanted animals, cancer-specific sEVs from 20 µl of plasma can be detected before tumors were palpable. The level plateaus between 5-15 absolute sEV count (ASC) per µl with tumors ≥8 mm3. In healthy human individuals (N = 106), the levels are on average 1.5 ASC/µl (+/- 0.95) without miR-21 expression. However, for stage I-III cancer patients (N = 205), nearly all (204 out of 205) have levels exceeding 3.5 ASC/µl with an average of 12.2 ASC/µl (±9.6), and a variable proportion of miR-21 labeling among different tumor types with 100% cancer specificity. Using a threshold of 3.5 ASC/µl to test a separate sample set in a blinded fashion yields accurate classification of healthy individuals from cancer patients. CONCLUSIONS: Our techniques and findings can impact the understanding of cancer biology and the development of new cancer detection and diagnostic technologies.

Small extracellular vesicles (sEVs) are tiny particles derived from cells that can be detected in bodily fluids such as blood. Detecting sEVs and analyzing their contents may potentially help us to diagnose disease, for example by observing differences in sEV numbers or contents in the blood of patients with cancer versus healthy people. Here, we combine two imaging methods ­ our previously developed method PANORAMA and imaging of fluorescence emitted by sEVs­to visualize and count sEVs, determine their size, and analyze their cargo. We observe differences in sEV numbers and cargo in samples taken from healthy people versus people with cancer and are able to differentiate these two populations based on our analysis of sEVs. With further testing, our approach may be a useful tool for cancer diagnosis and provide insights into the biology of cancer and sEVs.

TBCRC 057: Survey about willingness to participate in cancer clinical trials during the pandemic.

BACKGROUND: Breast cancer patients experienced heightened anxiety during the pandemic. Also, modifications to clinical trial activities allowing for virtual platforms, local assessments, and greater flexibility were introduced to facilitate participation. We sought to evaluate the association between pandemic-related anxiety and willingness to participate in trials and how pandemic-era modifications to trial activities affect the decision to participate. METHODS: We conducted an online survey from August to September, 2021 of patients with breast cancer assessing pandemic-related anxiety; clinical trials knowledge and attitudes; willingness to participate during and before the pandemic; and how each modification affects the decision to participate. Fisher's exact tests evaluated differences in proportions and two-sample t-tests evaluated differences in means. The association of pandemic-related anxiety with a decline in willingness to participate during compared to prior to the pandemic was modeled using logistic regression. RESULTS: Among 385 respondents who completed the survey, 81% reported moderate-severe pandemic-related anxiety. Mean willingness to participate in a trial was lower during the pandemic than prior [2.97 (SD 1.17) vs. 3.10 (SD 1.09), (p < 0.001)]. Severe anxiety was associated with higher odds of diminished willingness to participate during the pandemic compared to prior (OR 5.07). Each of the modifications, with the exception of opting out of research-only blood tests, were endorsed by >50% of respondents as strategies that would increase their likelihood of deciding to participate. CONCLUSIONS: While pandemic-related anxiety was associated with diminished willingness to participate in trials, the leading reasons for reluctance to consider trial participation were unrelated to the pandemic but included worries about not getting the best treatment, side effects, and delaying care. Patients view trial modifications favorably, supporting continuation of these modifications, as endorsed by the National Cancer Institute and others.

Iterative Patient Testing of a Stimuli-Responsive Swallowing Activity Sensor to Promote Extended User Engagement During the First Year After Radiation: Multiphase Remote and In-Person Observational Cohort Study.

BACKGROUND: Frequent sensor-assisted monitoring of changes in swallowing function may help improve detection of radiation-associated dysphagia before it becomes permanent. While our group has prototyped an epidermal strain/surface electromyography sensor that can detect minute changes in swallowing muscle movement, it is unknown whether patients with head and neck cancer would be willing to wear such a device at home after radiation for several months. OBJECTIVE: We iteratively assessed patients' design preferences and perceived barriers to long-term use of the prototype sensor. METHODS: In study 1 (questionnaire only), survivors of pharyngeal cancer who were 3-5 years post treatment and part of a larger prospective study were asked their design preferences for a hypothetical throat sensor and rated their willingness to use the sensor at home during the first year after radiation. In studies 2 and 3 (iterative user testing), patients with and survivors of head and neck cancer attending visits at MD Anderson's Head and Neck Cancer Center were recruited for two rounds of on-throat testing with prototype sensors while completing a series of swallowing tasks. Afterward, participants were asked about their willingness to use the sensor during the first year post radiation. In study 2, patients also rated the sensor's ease of use and comfort, whereas in study 3, preferences were elicited regarding haptic feedback. RESULTS: The majority of respondents in study 1 (116/138, 84%) were willing to wear the sensor 9 months after radiation, and participant willingness rates were similar in studies 2 (10/14, 71.4%) and 3 (12/14, 85.7%). The most prevalent reasons for participants' unwillingness to wear the sensor were 9 months being excessive, unwanted increase in responsibility, and feeling self-conscious. Across all three studies, the sensor's ability to detect developing dysphagia increased willingness the most compared to its appearance and ability to increase adherence to preventive speech pathology exercises. Direct haptic signaling was also rated highly, especially to indicate correct sensor placement and swallowing exercise performance. CONCLUSIONS: Patients and survivors were receptive to the idea of wearing a personalized risk sensor for an extended period during the first year after radiation, although this may have been limited to well-educated non-Hispanic participants. A significant minority of patients expressed concern with various aspects of the sensor's burden and its appearance. TRIAL REGISTRATION: ClinicalTrials.gov NCT03010150; https://clinicaltrials.gov/study/NCT03010150.

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.

A cognitive behavioral therapy-based intervention to address body image in patients with facial cancers: Results from a randomized controlled trial.

OBJECTIVES: Body image adjustment is a crucial issue for patients with facial cancer, but body image-specific interventions are scarce. We report results of a novel psychotherapeutic intervention to address body image concerns during acute postoperative recovery following facial reconstructive surgery. Our primary aims were to evaluate the intervention's feasibility, acceptability, and efficacy on body image concerns, psychological distress, and quality of life (QOL). METHODS: Adults with facial cancers who endorsed body image concerns were recruited to participate in a randomized controlled trial. The intervention group participated in 4 in-person counseling sessions. The control group received an educational booklet and a brief phone call. Participants completed measures of body image, distress, and QOL at baseline and at the 4-week follow-up to assess the impact of the intervention. Intervention outcomes were assessed with 2 sample t-tests or Mann-Whitney U tests as appropriate. RESULTS: Twenty-nine participants completed both the baseline and follow-up assessments. The intervention demonstrated good feasibility with a high retention rate (79%), visit completion rate (81%), and high satisfaction scores (75% reported mean satisfaction score of >3). Intervention did not result in an observed statistically significant difference in reduction in body image dissatisfaction and disturbance, psychological distress, or improvement in QOL compared with the control group. However, intervention resulted in statistically significant difference in perceived social impact (-1 vs. -8.3, p = 0.033) compared to control group. SIGNIFICANCE OF RESULTS: Our study highlights the potential clinical benefits of a novel psychotherapeutic intervention that targets body image concerns and suggests the need for further evaluation.

Network Modeling of Complex Time-Dependent Changes in Patient Adherence to Adjuvant Endocrine Treatment in ER+ Breast Cancer.

Early patient discontinuation from adjuvant endocrine treatment (ET) is multifactorial and complex: Patients must adapt to various challenges and make the best decisions they can within changing contexts over time. Predictive models are needed that can account for the changing influence of multiple factors over time as well as decisional uncertainty due to incomplete data. AtlasTi8 analyses of longitudinal interview data from 82 estrogen receptor-positive (ER+) breast cancer patients generated a model conceptualizing patient-, patient-provider relationship, and treatment-related influences on early discontinuation. Prospective self-report data from validated psychometric measures were discretized and constrained into a decisional logic network to refine and validate the conceptual model. Minimal intervention set (MIS) optimization identified parsimonious intervention strategies that reversed discontinuation paths back to adherence. Logic network simulation produced 96 candidate decisional models which accounted for 75% of the coordinated changes in the 16 network nodes over time. Collectively the models supported 15 persistent end-states, all discontinued. The 15 end-states were characterized by median levels of general anxiety and low levels of perceived recurrence risk, quality of life (QoL) and ET side effects. MIS optimization identified 3 effective interventions: reducing general anxiety, reinforcing pill-taking routines, and increasing trust in healthcare providers. Increasing health literacy also improved adherence for patients without a college degree. Given complex regulatory networks' intractability to end-state identification, the predictive models performed reasonably well in identifying specific discontinuation profiles and potentially effective interventions.

Active Living After Cancer: Adaptation and evaluation of a community-based physical activity program for minority and medically underserved breast cancer survivors.

BACKGROUND: An expanding body of research documents the benefits of physical activity for cancer survivors' physical functioning and quality of life, but few successful models provide community-based physical activity programs to cancer survivors. This report presents an evaluation of Active Living After Cancer, an evidence-based physical activity program for breast cancer survivors, adapted for community delivery to minority and medically underserved survivors. METHODS: Survivors were recruited from health care and community settings. The program consisted of 12 weekly group sessions providing training in cognitive and behavioral skills for behavior change, brief physical activity, and cancer survivorship-related content. At the baseline and follow-up, participants completed assessments of their physical activity, quality of life, and physical functioning (6-minute walk and 30-second sit-to-stand test). At follow-up, they also completed questionnaires to measure program content mastery and satisfaction. RESULTS: The outcome analysis included 127 participants. Physical activity and quality of life (mental and physical) improved from the baseline to follow-up (all P < .01). Physical functioning improved, with increases in sit-to-stand repetitions (mean, 12.5 at the baseline vs 14.9 at the follow-up; P < .01) and 6-minute walk distances (mean, 428 m at the baseline vs 470 m at the follow-up; P < .01). CONCLUSIONS: The results highlight the effectiveness of an evidence-based program adapted for community-based delivery to minority and medically underserved breast cancer survivors. The program could be delivered to improve outcomes in diverse survivor populations. LAY SUMMARY: Physical activity in breast cancer survivors is related to better quality of life and longer cancer-free survival. However, there are few community-based programs to help breast cancer survivors to become more physically active. The Active Living After Cancer program was adapted from an evidence-based program and delivered in community-based settings to minority and medically underserved breast cancer survivors. It consisted of 12 weekly group sessions in which participants learned skills to increase their physical activity. The program participants increased their physical activity and improved their mental and physical well-being and physical functioning.

Attributions of survival and methods of coping of long-term ovarian cancer survivors: a qualitative study.

BACKGROUND: Only 8-23% of advanced epithelial ovarian cancer patients survive for 10 years or longer. Given the need for targeted interventions to improve survival, we interviewed this relatively rare survivor population to gain personalized insights into the reasons for their survival. The aim of this study was to characterize subjective attributions of survival and specific coping mechanisms long-term survivors of ovarian cancer. METHODS: Twenty-two semi-structured, qualitative interviews assessing survival attributions and coping strategies were conducted from April to November 2014. Data were analyzed in a multistep process using ATLAS.ti.8: codes were identified during review of the transcripts and refined with literature review; the frequency of codes and code co-occurrence was calculated, and codes were grouped into themes. Resulting themes were checked by a national leader of an ovarian cancer advocacy organization and compared against available literature. RESULTS: Thematic analysis found that participants credited their long-term survival to a variety of factors including medical, social, religious/spiritual, and lifestyle/personal characteristics. Some participants rejected these same attributions, concluding that the reason for survival was due to luck or unknowable. Several of Carver et al.'s theoretical dimensions of coping were evident in our sample: planning, positive reinterpretation, social support, religion and acceptance whereas three relatively new strategies were uncovered: conserving emotional energy, value-based activity coping, and self-care. CONCLUSIONS: Long-term survivors' perspectives were largely consistent with those of newly diagnosed ovarian cancer patients and ovarian cancer survivors of shorter duration. However, the long-term survivors were also willing to reject conventional attributions for survival and recognized the importance of disciplined self-preservational coping strategies.

Feasibility of Mobile and Sensor Technology for Remote Monitoring in Cancer Care and Prevention.

Objectives. Remote monitoring (RM) of health-related outcomes may optimize cancer care and prevention outside of clinic settings. CYCORE is a software-based system for collection and analyses of sensor and mobile data. We evaluated CYCORE's feasibility in studies assessing: (1) physical functioning in colorectal cancer (CRC) patients; (2) swallowing exercise adherence in head and neck cancer (HNC) patients during radiation therapy; and (3) tobacco use in cancer survivors post-tobacco treatment (TTP). Methods. Participants completed RM: for CRC, blood pressure, activity, GPS; for HNC, video of swallowing exercises; for TTP, expired carbon monoxide. Patient-reported outcomes were assessed daily. Results. For CRC, HNC and TTP, respectively, 50, 37, and 50 participants achieved 96%, 84%, 96% completion rates. Also, 91-100% rated ease and self-efficacy as highly favorable, 72-100% gave equivalent ratings for overall satisfaction, 72-93% had low/no data privacy concerns. Conclusion. RM was highly feasible and acceptable for patients across diverse use cases.

Patient-reported outcomes in the Translational Breast Cancer Research Consortium.

Members of the Translational Breast Cancer Research Consortium conducted an expert-driven literature review to identify a list of domains and to evaluate potential measures of these domains for inclusion in a list of preferred measures. Measures were included if they were easily available, free of charge, and had acceptable psychometrics based on published peer-reviewed analyses. A total of 22 domains and 52 measures were identified during the selection process. Taken together, these measures form a reliable and validated list of measurement tools that are easily available and used in multiple cancer trials to assess patient-reported outcomes in relevant patients.

Predictors of survival trajectories among women with epithelial ovarian cancer.

OBJECTIVE: Although ovarian cancer is a deadly disease, approximately a third of women survive ≥9 years after diagnosis. The factors associated with achieving long-term survival are not well understood. In this study, data from the Surveillance, Epidemiology, and End Results (SEER) program were used to determine predictors of survival trajectories among women with epithelial ovarian cancer and across histotype (high-grade serous carcinoma (HGSC) and non-HGSC). METHODS: Data on 35,868 women diagnosed with epithelial ovarian cancer in 2004-2016 were extracted from SEER. Extended Cox proportional hazards regression was used to estimate overall and histotype-specific associations between patient and tumor characteristics and all-cause mortality within each survival time (t) interval (t < 3, 3 ≤ t < 6, 6 ≤ t < 9, and 9 ≤ t < 13 years). RESULTS: Age at diagnosis, marital status, race/ethnicity, stage, and surgery were more strongly associated with mortality in the short-term survival period, and these associations waned with increasing survival time. Exceptions to this pattern were age >70 years at diagnosis, where a high risk of mortality was observed in both the t < 3 and t ≥ 9 year time periods, and non-Hispanic Asian/Pacific Islanders, where a more pronounced inverse association with mortality was observed in t ≥ 9 years after diagnosis. Similar associations were observed for HGSC, although the waning effect was not apparent for most characteristics. Mortality associations for non-HGSC were more pronounced for stage and race/ethnicity, primarily for non-Hispanic Asian/Pacific Islanders. CONCLUSIONS: Most patient and tumor characteristics were more strongly associated with mortality in the years following diagnosis, but have declining impact with increasing survival time. Given this waning effect, it is critical to identify factors impacting risk of mortality as ovarian cancer patients advance through the survival trajectory.

Simulating Time-Dependent Patterns of Nonadherence by Patients With Breast Cancer to Adjuvant Oral Endocrine Therapy.

PURPOSE: Nearly 40% of patients with breast cancer discontinue their adjuvant oral endocrine treatment (ET). We measured discontinuation rates of ET at a comprehensive cancer center. We then used an iterative approach to model patterns of determinants associated with discontinuation of ET. METHODS: Patients with nonmetastatic breast cancer receiving active adjuvant ET were approached by nurse practitioners to complete an anonymous survey at one time point. We simulated a prospective model by iteratively regressing adverse effects onto adherence status across windowed time periods of 2 to 3 consecutive years, bootstrapping the smaller group of nonadherent patients and subsampling the larger adherent group. RESULTS: From February to April 2013, 216 participants were enrolled in the study. Forty patients (18.5%) reported that they had discontinued ET during the first 5 years of ET, and an additional four patients (1.9%) missed > 20% of their doses. Using two-sided significance tests, simulations showed that all 13 ET adverse effects and reasons for discontinuation were significantly related to discontinuation at some time point during ET. Worry about ET cost (odds ratio [OR], 1.79), emotional distress (OR, 1.72), and bone and joint pain (OR, 1.69) were the three most impactful reasons for discontinuation, with varying patterns of influence over time. CONCLUSION: These analyses provide preliminary evidence that there are varying patterns of discontinuation of ET. Although some reasons for discontinuation exerted a steady influence over the 6-year ET trajectory (ie, bone and joint pain), other reasons, such as cost, cognitive complaints, and general dislike of pills, became more important in the later years of ET.

Metallic Nanoislands on Graphene for Monitoring Swallowing Activity in Head and Neck Cancer Patients.

There is a need to monitor patients with cancer of the head and neck postradiation therapy, as diminished swallowing activity can result in disuse atrophy and fibrosis of the swallowing muscles. This paper describes a flexible strain sensor comprising palladium nanoislands on single-layer graphene. These piezoresistive sensors were tested on 14 disease-free head and neck cancer patients with various levels of swallowing function: from nondysphagic to severely dysphagic. The patch-like devices detected differences in (1) the consistencies of food boluses when swallowed and (2) dysphagic and nondysphagic swallows. When surface electromyography (sEMG) is obtained simultaneously with strain data, it is also possible to differentiate swallowing vs nonswallowing events. The plots of resistance vs time are correlated to specific events recorded by video X-ray fluoroscopy. Finally, we developed a machine-learning algorithm to automate the identification of bolus type being swallowed by a healthy subject (86.4%. accuracy). The algorithm was also able to discriminate between swallows of the same bolus from either the healthy subject or a dysphagic patient (94.7% accuracy). Taken together, these results may lead to noninvasive and home-based systems for monitoring of swallowing function and improved quality of life.

Quality of life among long-term survivors of advanced stage ovarian cancer: A cross-sectional approach.

PURPOSE: Long-term survival of women with advanced-stage ovarian cancer is relatively rare. Little is known about quality of life (QOL) and survivorship concerns of these women. Here, we describe QOL of women with advanced-stage ovarian cancer surviving for 8.5 years or longer and compare women with 0-1 recurrence to those with multiple recurrences. METHODS: Participants (n=56) recruited from 5 academic medical centers and the Ovarian Cancer Research Fund Alliance completed surveys regarding QOL (FACT-O), mood (CESD), social support (SPS), physical activity (IPAQ-SF), diet, and clinical characteristics. Median survival was 14.0 years (range 8.8-33.3). RESULTS: QOL and psychological adjustment of long-term survivors was relatively good, with mean FACT-G scores (multiple recurrences: 80.81±13.95; 0-1 recurrence: 89.05 ±10.80) above norms for healthy community samples (80.1±18.1). Survivors with multiple recurrences reported more compromised QOL in domains of physical and emotional well-being (p <.05), and endorsed a variety of physical and emotional concerns compared to survivors with 0-1 recurrence. Difficulties in sexual functioning were common in both groups. Almost half (43%) of the survivors reported low levels of physical activity. CONCLUSIONS: Overall, women with advanced-stage ovarian cancer who have survived at least 8.5 years report good QOL and psychological adjustment. QOL of survivors with multiple recurrences is somewhat impaired compared to those with 0-1 recurrence. Limitations include a possible bias towards participation by healthier survivors, thus under-representing the level of compromise in long-term survivors. Health care practitioners should be alert to psychosocial issues faced by these long-term survivors to provide interventions that enhance QOL.

Comparison of four brief depression screening instruments in ovarian cancer patients: Diagnostic accuracy using traditional versus alternative cutpoints.

OBJECTIVES: We compared the diagnostic accuracy of 4 depression screening scales, using traditional and alternative scoring methods, to the gold standard Structured Clinical Interview-DSM IV major depressive episode (MDE) in ovarian cancer patients on active treatment. METHODS: At the beginning of a new chemotherapy regimen, ovarian cancer patients completed the following surveys on the same day: the Center for Epidemiological Studies Depression Scale (CES-D), the Beck Depression Inventory Fast-Screen for Primary Care (BDI-FastScreen), the Patient Health Questionnaire-9 (PHQ-9), and a 1-item screener ("Are you depressed?"). Each instrument's sensitivity, specificity, positive predictive value (PPV) and negative predictive value were calculated with respect to major depression. To control for antidepressant use, the analyses were re-run for a subsample of patients who were not on antidepressants. RESULTS: One hundred fifty-three ovarian cancer patients were enrolled into the study. Only fourteen participants met SCID criteria for current MDE (9%). When evaluating all patients regardless of whether they were already being treated with antidepressants, the two-phase scoring approach with an alternate cutpoint of 6 on the PHQ-9 had the best positive predictive value (PPV=32%). Using a traditional cutpoint of 16 on the CES-D resulted in the lowest PPV (5%); using a more stringent cutpoint of 22 resulted in a slightly improved but still poor PPV, 7%. CONCLUSIONS: Screening with a two-phase PHQ-9 proved best overall, and its accuracy was improved when used with patients who were not already being treated with antidepressants.

SSRI use and clinical outcomes in epithelial ovarian cancer.

Selective serotonin reuptake inhibitor (SSRI) use is common among ovarian cancer patients. We examined the effect of SSRIs on survival and progression in ovarian cancer patients and effects of 5-HT on ovarian cancer cell (OCC) proliferation. Ovarian cancer patients from a 6-site study between 1994 and 2010 were included. Cox proportional hazards models were used for multivariate analysis. SSRI use was associated with decreased time to disease recurrence (HR 1.3, CI 1.0-1.6, p=0.03), but not overall survival (HR 1.1, CI 0.9-1.3, p=0.56). Compared to normal ovarian cells, most OCCs had elevated 5-HT2A receptor mRNA expression (up to 1600 fold greater expression). Clonogenic survival increased in cells treated with 10 uM (1.6 fold, p<0.001) and 20uM (1.9 fold, p=0.018) 5-HT. Mice receiving 5-HT injections had increases in tumor weight (p=0.07) and nodules (p=0.08) with increased Ki67 expression. Injections with sertraline doubled mean tumor weight in mice (p=0.16). 5-HT and sertraline both increased Ki67 expression in mouse tumors (p < 0.001).Patients using SSRIs had significantly decreased time to disease progression. It is possible that SSRIs alter serotonin levels in the tumor microenvironment, resulting in activation of proliferation pathways. Further characterization of serotonergic pathways in ovarian cancer is recommended to demonstrate safety of these medications.