Chemotherapy For Gynecologic Cancer Research Articles

Factors influencing self-regulatory fatigue in patients undergoing chemotherapy for gynecologic cancer: a cross-sectional study.

To understand the current status of self-regulatory fatigue among gynecologic cancer chemotherapy patients and explore influencing factors. Using convenient sampling, a total of 232 gynecological cancer chemotherapy patients from two tertiary hospitals in Zhengzhou, Henan, China, were selected as study subjects from February 2023 to April 2023. General information questionnaire, Self-Regulatory Fatigue Scale (SRF-S), Strategies Used by People to Promote Health (SUPPH) Scale, Connor-Davidson resilience scale (CD-RISC) and Perceived Social Support Scale (PSSS) were employed for data collection. The data were analyzed using SPSS 26.0 software. Chi-square test and binary logistic regression were executed to explore the correlates of self-regulatory fatigue, the significance level (α) was set at 0.05. The self-regulatory fatigue score of the 232 patients was 44 (36, 56). Binary logistic regression analyses revealed significant associations, demonstrating that residing in urban areas (OR=0.241, P=0.015), having no comorbidities (OR=0.158, P=0.015), increased perceived social support (OR=0.937, P=0.001), strong self-efficacy (OR=0.959, P=0.021), and heightened psychological resilience (OR=0.895, P<0.001) acted as protective factors against self-regulatory fatigue (P < 0.05). Patients residing in rural areas, having more than two comorbidities, lower self-efficacy and psychological resilience levels, and lower perceived social support are indicative of higher levels of self-regulatory fatigue. Identifying these influencing factors can provide references and support for developing individualized support and intervention measures to improve patients' physical and mental well-being.

Dynamic Associations Between Daily Pain and Mood during Chemotherapy for Gynecologic Cancers

BackgroundPain and mood disturbances, such as anxiety and depression, are common symptoms in gynecologic cancer. Their associations and the role of personality traits in pain adaptation during chemotherapy remain unclear. This ancillary data analysis aimed to investigate these relationships. AimTo (1) depict the temporal trend of daily pain severity; (2) evaluate dynamic associations between mood and pain; and (3) explore personality traits (neuroticism and conscientiousness) as moderators of the mood-pain relationship during chemotherapy for gynecologic cancer. MethodSymptom severity was assessed daily throughout chemotherapy, while personality, clinical, and demographic characteristics were assessed at baseline. Twenty-seven women with gynecologic cancer who completed daily symptom assessments for at least four cycles were included in the analyses. ResultsPain severity decreased slightly during chemotherapy. Multilevel modeling supported significant associations between pain and anxiety (b = 0.24, standard error [SE] = 0.06, p = .001) and depression (b = 0.30, SE = 0.08, p = .002). Time-varying effect modeling showed significant associations between anxiety and pain that initially increased and then decreased; and significant associations between depression and pain steadily decreased over the first four cycles of chemotherapy. Neuroticism moderated the association between anxiety and pain (b = 0.15, SE = 0.06, p < .05), with anxiety more strongly associated with pain in those with higher neuroticism. ConclusionsThis study highlights the dynamic nature of pain and its associations with anxiety and depression in individuals with gynecologic cancer undergoing chemotherapy. The findings have implications for understanding pain and developing tailored psychosocial symptom management interventions to prevent pain during chemotherapy.

Relationships among Inflammatory Biomarkers and Objectively Assessed Physical Activity and Sleep during and after Chemotherapy for Gynecologic Malignancies.

Little is known regarding associations between inflammatory biomarkers and objectively measured physical activity and sleep during and after chemotherapy for gynecologic cancer; thus, we conducted a longitudinal study to address this gap. Women with gynecologic cancer (patients) and non-cancer controls (controls) completed assessments before chemotherapy cycles 1, 3, and 6 (controls assessed contemporaneously), as well as at 6- and 12-month follow-ups. Physical activity and sleep were measured using wrist-worn actigraphs and sleep diaries, and blood was drawn to quantify circulating levels of inflammatory markers. Linear and quadratic random-effects mixed models and random-effects fluctuation mixed models were used to examine physical activity and sleep over time, as well as the associations with inflammatory biomarkers. On average, patients (n = 97) and controls (n = 104) were 62 and 58 years old, respectively. Compared to controls, patients were less active, more sedentary, had more time awake after sleep onset, and had lower sleep efficiency (p-values < 0.05). Across groups, higher levels of TNF-α were associated with more sedentary time and less efficient sleep (p-values ≤ 0.05). Higher levels of IL-1β, TNF-α, and IL-6 were associated with lower levels of light physical activity (p-values < 0.05). Associations between inflammatory biomarkers, physical activity, and sleep did not differ between patients and controls. Given these results, we speculate that inflammation may contribute to less physical activity and more sleep problems that persist even 12 months after completing chemotherapy.

Relationships among Inflammatory Biomarkers and Self-Reported Treatment-Related Symptoms in Patients Treated with Chemotherapy for Gynecologic Cancer: A Controlled Comparison.

Previous research suggests that inflammation triggers cancer-treatment-related symptoms (i.e., fatigue, depression, and disruptions in sleep and physical activity), but evidence is mixed. This study examined relationships between inflammatory biomarkers and symptoms in patients with gynecologic cancer compared to age-matched women with no cancer history (i.e., controls). Patients (n = 121) completed assessments before chemotherapy cycles 1, 3, and 6, and 6 and 12 months later. Controls (n = 105) completed assessments at similar timepoints. Changes in inflammation and symptomatology were evaluated using random-effects mixed models, and cross-sectional differences between patients and controls in inflammatory biomarkers and symptoms were evaluated using least squares means. Associations among inflammatory biomarkers and symptoms were evaluated using random-effects fluctuation mixed models. The results indicated that compared to controls, patients typically have higher inflammatory biomarkers (i.e., TNF-alpha, TNFR1, TNFR2, CRP, IL-1ra) and worse fatigue, depression, and sleep (ps < 0.05). Patients reported lower levels of baseline physical activity (p = 0.02) that became more similar to controls over time. Significant associations were observed between CRP, depression, and physical activity (ps < 0.05), but not between inflammation and other symptoms. The results suggest that inflammation may not play a significant role in fatigue or sleep disturbance among gynecologic cancer patients but may contribute to depression and physical inactivity.

Clinical trial assessing the safety of edoxaban with concomitant chemotherapy in patients with gynecological cancer-associated thrombosis (EGCAT study)

BackgroundGynecological cancer is one of the highest risk factors for cancer-associated thrombosis (CAT). Although low-molecular-weight heparin (LMWH) is recommended as an anticoagulant for treating CAT, recent studies have shown that direct oral anticoagulants (DOACs) are an acceptable alternative. Patients with cancer require a series of chemotherapies concomitantly with DOAC administration; however, the extent to which these drugs influence DOAC blood concentrations is unknown. In this study, we measured the plasma concentration of edoxaban during chemotherapy for gynecological cancers to determine its safety.MethodsPatients histologically diagnosed with ovarian or uterine corpus cancer and CAT were recruited after primary surgery and before the initiation of postoperative adjuvant chemotherapy, including paclitaxel. Patients were administered edoxaban (30 or 60 mg) orally for CAT. The plasma concentrations of edoxaban and active factor Xa were determined and their percentage change before and after chemotherapy was calculated. Additionally, blood coagulation tests were analyzed.ResultsSixteen patients with gynecological cancer (12 with ovarian cancer and 4 with uterine corpus cancer) were enrolled. Among these, 15 samples were collected one day after chemotherapy initiation. During chemotherapy, the trough concentration of edoxaban changed from 17.6 ± 10.6 to 20.0 ± 15.6 ng/ml, and the mean percentage change in edoxaban concentration was 14.5%. Therefore, the trough concentrations of edoxaban, which represent excretion capacity, were not significantly increased by chemotherapy with paclitaxel. The area under the plasma edoxaban concentration–time curve and the active factor Xa concentration were also unaffected.ConclusionPatients with CAT and ovarian or uterine corpus cancer administered edoxaban orally showed no significant increase in the trough concentration of edoxaban while undergoing chemotherapy. This suggests the safety of edoxaban use during the treatment of gynecological cancers.Trial registrationEGCAT study; Japan Registry of Clinical Trials, jRCTs051190024.

Evaluating An Embedded Exercise Trainer Program In The Cancer Infusion Suite

Purpose The purpose of the study was to evaluate qualitative responses to an interest survey for engaging in exercise in the chemotherapy suite and detail a proposed clinical model. Methods The Cancer Exercise Wellness Program partnered with a gynecologic oncologist to work with patients undergoing chemotherapy for gynecologic cancers. American College of Sports Medicine Cancer Exercise Trainers were embedded in the chemotherapy suite. Patients were surveyed to gauge interest in the pilot program and to determine baseline exercise characteristics. Respondents indicated current physical activity habits, interest in participating in exercise during chemotherapy, and barriers to exercise. Patients that indicated interest in participation were provided the option to be evaluated and enrolled in the exercise program. Results The interest survey was completed by 27 gynecologic cancer patients, with 66.7% indicating that they were not currently physically active. The most common barrier cited was physical limitations (45%), followed by fatigue (29.6%). The vast majority of patients (81.5%) believed they would receive benefit from participating in exercise during their chemotherapy sessions and that the infusion suite would be an appropriate location to do this. Of the 27 of patients surveyed, 16 (59%) indicated interest in the program with 15 (55%) patients enrolling in the program. Discussion Embedding an exercise trainer in the chemotherapy infusion suite has proven to be a feasible option to promote increased physical activity and education about the benefits of exercise in cancer patients. Specifically, most patients reported that exercise in the suite would be safe and beneficial to their health. Additionally, having a cancer exercise trainer work with this population may help address the perceived barriers to exercise. These findings are consistent with those collected in a larger clinical trial by Schmitz et al (1). Next steps include expansion of this program to all cancer types as well as quantifying specific health benefits and quality of life parameters.

Direct oral anticoagulant (DOACs) prescribing practices of members of the Society of Gynecologic Oncology and American Society of Clinical Oncology (374)

<b>Objectives:</b> The risk of venous thromboembolism (VTE) in patients with gynecologic malignancy is 25-38% and is associated with significant morbidity and mortality. Direct oral anticoagulants (DOACs) have emerged as an alternative to injectable medications for thromboprophylaxis and treatment of VTE. Several recent clinical trials have demonstrated the benefit of DOACs in high-risk patients receiving systemic chemotherapy as well as postoperative prophylaxis after surgery for gynecologic cancer. Major consensus guidelines from multiple organizations support the use of DOACs for these indications, but prescription practices are not well characterized. <b>Methods:</b> A survey was sent concurrently to members of the Society of Gynecologic Oncology (SGO) and the American Society of Clinical Oncology (ASCO) Research Survey Pool between May and June of 2021. The study was designed to assess DOAC prescription practices amongst members of these societies who routinely prescribe chemotherapy. Bivariate analyses comparing responses from ASCO and SGO participants were compared using Chi-square and Fisher's exact tests. <b>Results:</b> A total of 103 physicians were included in the ASCO group and 139 in the SGO group (response rates 15% and 8%, respectively). A majority of participants in both groups reported familiarity with prescribing DOACs (99% of ASCO and 96% of SGO respondents). ASCO respondents were more likely to consider DOACs as first-line therapy for the treatment of cancer-associated VTE than SGO members (82% vs 63%, p < 0.01). In comparison, SGO members were more likely to consider low molecular weight heparin (LMWH) (66% vs 25%, p < 0.01). Most respondents in both groups (75%) felt DOACs were equally safe and effective compared to LMWH but more ASCO members felt DOACs were cost-effective (70% vs 49%, p < 0.01). More SGO respondents reported having prescribed prophylactic anticoagulation during chemotherapy than ASCO members (53% vs 35%, p < 0.01). A majority of participants in both groups reported knowledge of the Khorana score as a risk assessment tool (60% and 61%); however, only 30% of respondents felt this scoring system reliably predicts risk of VTE in ambulatory outpatients initiating chemotherapy and at least 70% of participants in both groups had never used this tool. SGO respondents were more likely to feel that there was insufficient evidence to recommend prophylactic anticoagulation to high-risk outpatients initiating chemotherapy for gynecologic cancer (41% vs 29%, p < 0.01). Among the 150 respondents who performed surgery for gynecologic cancer, 80% felt LMWH is the standard of care for postoperative thromboprophylaxis compared to only 15% who felt DOACs were the standard of care. The most commonly cited barriers to DOAC prescription for prevention of cancer-associated VTE were insurance approval for the medication, out-of-pocket expense to the patient, and lack of data to support efficacy. <b>Conclusions:</b> ASCO respondents were more likely to prescribe DOACs for both treatment and prophylaxis of cancer-associated VTE than SGO members. However, SGO members were more likely to prescribe prophylactic anticoagulation to high-risk patients initiating chemotherapy compared to ASCO members. The use of the Khorana scoring system was low amongst respondents from both societies.

Intensive Daily Symptom and Function Monitoring Is Feasible and Acceptable to Women Undergoing First-Line Chemotherapy for Gynecologic Cancer.

Women receiving chemotherapy for gynecologic cancer (GC) experience severe symptoms with associated functional changes. Understanding day-to-day symptom and function variation within and across chemotherapy treatment cycles could inform improved symptom management, but such studies are rare and may be infeasible in clinical care. The aim of this study was to evaluate feasibility and acceptability of daily symptom monitoring combined with objective and self-reported functional assessments every 21 days during active chemotherapy for GC. Thirty women enrolled in a prospective observational study during first-line chemotherapy completed a daily symptom and falls diary during their entire chemotherapy treatment period. Patient-reported outcomes and objective symptom and function testing were assessed before each chemotherapy appointment. Study outcomes included accrual and attrition rates, completion of study assessments, and qualitative perceptions of study participation. Participants were 92% White, 60% had high school or higher education, 68% were married/partnered, and 62% had stage III or IV cancer at diagnosis. The study had an 83% accrual rate, 6.6% early withdrawal rate, and 17% total attrition rate. Missing assessments for prechemotherapy patient-reported outcomes and objective assessments ranged from 27% to 35% and 35% to 47% respectively, with a general decrease across cycles. Daily diary completion rate was 83% overall. Participants rated study participation positively. Intensive daily symptom and function monitoring was feasible and acceptable to GC patients and may provide a sense of symptom controllability. Daily symptom and function monitoring in research studies may provide patients with information to support symptom discussions with the clinical team. Future work should develop proactive symptom management interventions using personalized symptom trajectories.

Impact of COVID-19 on patients receiving chemotherapy for gynecological cancer

Background: Cancer patients’ increased susceptibility to serious COVID-19 complications can be attributed to the immunosuppressed state caused by the disease and anticancer treatments such as chemotherapy or surgery. Objectives: To assess the effect of COVID-19 pandemic on gynecological cancer patients receiving chemotherapy. Methods: A cross-sectional study was conducted on patients receiving chemotherapy for gynecological cancer between (March 2020 to February 2021) at King Abdulaziz University Hospital (KAUH) in Jeddah, Saudi Arabia. Clinical data collected from medical records included patients’ ages, medical history data, cycles of chemotherapy, COVID-19 infection, complications and death. Results: Total of 84 patients were identified. The mean age of studied patients was 53.81 ± 13.76 years, and the most common chronic diseases were HTN (35.7%) and DM (23.8%). The majority of diagnoses were ovarian cancer (41.7%) followed by uterine cancer (33.3%). Of studied patients, 17.9%, 19.1%, 27.4 and 33.3% had I, II , III and IV cancer stages respectively. The mean number of cycles of chemotherapy was 7.14 ± 5.55. 52.4% had first line chemotherapy. 57 percent of patients had delays due to various causes, including COVID-19 infection, and 9 percent of patients had COVID-19 while on therapy. 15 percent of the delays were caused by patients who were affected by Covid-19 while receiving chemotherapy and 2% of the patients died as a result of COVID-19 . Patients with recurrent disease had a significantly higher percentage of patients detected with COVID-19, and all cases detected with COVID-19 died with respiratory failure. Patients who had their chemotherapy delayed had a significantly higher mean number of cycles. Conclusion: Improved communication and management programs are required to keep cancer patients and their healthcare providers connected, as well as to allow cancer patients to survive a pandemic. Key words: Impact, COVID-19, patients, chemotherapy, Jeddah, Saudi Arabia.

Platinum resistance in gynecologic malignancies: Response, disease free and overall survival are predicted by biochemical signature: A metabolomic analysis

ObjectivePlatinum resistance, defined as the lack of response or relapse within six months of platinum-based chemotherapy, is an important determinant of survival in gynecologic cancer. We used quantitative Mass Spectrometry to identify metabolic signatures that predict platinum resistance in patients receiving chemotherapy for gynecologic cancers. MethodsIn this study 47 patients with adenocarcinoma of the ovary or uterus who were candidates for carboplatin plus paclitaxel submitted blood for quantitation of metabolites and surgical specimens for the isolation 3-dimensional organoids used to measure individual patient platinum resistance, ex vivo. Results were correlated with response, time to progression and survival. ResultsOf 47 patients, 27 (64.3%) achieved complete remission with a mean time to progression of 1.9 years (± 1.5), disease-free survival of 1.7 years (± 1.4) and overall survival of 2.6 years (± 1.6) and a mean cisplatin lethal concentration 50% (LC50) = 1.15 μg/ml (range 0.4–3.1). Cisplatin LC50's correlated with a non-significant decrease in complete remission (RR [95% CI] =0.76 [0.46–1.27]), diminished disease-free survival (median: 1.15 vs. 2.99 years, p = 0.038) and with biochemical signatures of 186 metabolites. Receiver operating curves (ROC) of lipid ratios, branched chain amino acids and the tryptophan to kynurenine ratio identified patients at the highest risk of relapse and death (AUC = 0.933) with a sensitivity of 92.0% and specificity of 86.0% (p < 0.001). ConclusionsMetabolic signatures in gynecologic cancer identify patients at the highest risk of relapse and death offering new diagnostic and prognostic tools for management of the advanced gynecologic tumors.

The impact of the SARS-COV2 pandemic on the delivery of chemotherapy for gynecologic cancer at a tertiary care institution in the United States epicenter

Objectives:In New York City, the SARS-CoV2 pandemic epicenter of the United States, the surge of cases predated much of the country by several weeks, leading to changes in practice patterns that have informed decisions made by other medical institutions. As the SARS-CoV2 pandemic unfolded, many professional subspecialty organizations released practice guidelines in order to minimize transmission of COVID-19 and protect vulnerable populations. The impact of modifications to traditional gynecologic cancer treatment is not known. Here, we describe the impact of the SARS-COV2 pandemic on chemotherapy practices for gynecologic cancer during the pandemic surge.Methods:We identified patients age 18 or older at Montefiore Medical Center who had a confirmed or suspected diagnosis of gynecologic cancer and received care between March 16, 2020 and June 7, 2020; these dates reflect a series of executive orders issued by the Governor of New York allowing the State Commissioner of Health to cancel elective procedures at hospitals and ambulatory surgery centers. Clinical data were abstracted from patients’ charts. Patients with incomplete treatment records were excluded.Results:A total of 146 women who were included to whom 169 cycles of cytotoxic chemotherapy were delivered during the study period and 68 women (46.6%) received at least one cycle of chemotherapy. Nine patients screened positive for symptoms of COVID or active infection during the study period. Among patients receiving chemotherapy, 52.9% (n=36) had modifications to traditional cancer treatment as a result of state and institutional regulations. Dose reduction was the leading pandemic-related treatment modification and occurred in 69.4% of patients (n=25). Other treatment modifications included prophylactic use of pegfilgrastim (n=1), and treatment deferral or delay (n=7). Women receiving a platinum-based doublet (n=36) during the study period were more likely to sustain dose reduction in chemotherapy (25%) compared to patients undergoing other regimens (0%). A total of 111 women received at least one dose of disease-modifying therapy during the cohort period including chemotherapy, immunotherapy, anti-angiogenesis agents, hormonal therapy, PARP inhibitors, or investigational agents. Treatments were most often discontinued due to completion of adjuvant therapy (n=5), progression of disease (n=4), or toxicity (n=5). Notably 5 patients chose to defer therapy in the setting of the pandemic surge. Only one patient was identified as receiving neoadjuvant chemotherapy specifically due to COVID pandemic-related restrictions.Conclusions:The SARS-COV2 pandemic has led to modification of current standard chemotherapy delivery for gynecologic malignancies with the shared goal of protecting the most vulnerable populations from COVID infection. The impact of these modifications on cancer specific outcomes is not yet known. Future investigation will focus on identifying whether treatment modification to circumvent iatrogenic immunosuppression compromises oncologic outcomes.

Using the Time-Varying Effect Model (TVEM) to Examine Dynamic Associations Between Daily Pain and Mood Assessments During 4-cycles of Chemotherapy for Gynecologic Cancer

Chemotherapy for gynecologic (GYN) cancer leads to high symptom burden and low quality of life. Pain is common, distressing, and often co-occurs with mood symptoms (e.g. anxiety, depression). Traditional analytical methods assume a constant effect of mood on pain, even for longitudinal data. Little evidence has examined the dynamic, daily relationship between anxiety/depression and pain during chemotherapy. Thus, we aimed to examine dynamic associations between daily pain and mood during 4 cycles of chemotherapy for CYN cancer. In this secondary analysis, daily self-reported symptoms were collected for 84 days (21 days/cycle * 4 cycles) during a longitudinal study of symptoms in GYN cancer treatment. Women (N=24, M age=60.5 years) initiating outpatient chemotherapy for newly diagnosed GYN cancer rated the severity of multiple symptoms (including anxiety, depression and pain) at their worst in the past 24 hours on a validated 0 to 10 scale. We used the time-varying effect model (TVEM) to examine daily associations between mood and pain over time. The nonparametric trajectory of pain was decreasing over time, with a significant association between daily anxiety and pain from day 2 through day 80 (from day 1 to day 84, regression coefficient of anxiety range [CoR-anxiety]=0.23-0.66). The magnitude of association was stable until day 70 before decreasing. There was also a significant association between daily depression and pain until day 58 (CoR-depression=0.43-1.21), with a steady decrease in the magnitude of association over time. TVEM identified patterns of association between mood and pain that varied in magnitude over chemotherapy. Overall, the influence of anxiety/depression on pain decreased with more cycles of chemotherapy, which may suggest adaptation of pain intensity. These dynamic associations can advance understanding of relationships between mood and physical symptoms and provide insight into the everyday challenges faced by women undergoing chemotherapy for GYN cancer. A Pilot Study of Falls and Near Falls in Women with Ovarian Cancer Receiving Neurotoxic Chemotherapy. Funding: Rehabilitation Nursing Foundation. No grant number since this is a private foundation.

A pneumococcal pneumonia and influenza vaccination quality improvement program for women receiving chemotherapy for gynecologic cancers at a major tertiary cancer Centre

ObjectiveInternational guidelines recommend pneumococcal pneumonia and influenza vaccination for all patients with solid organ malignancies prior to initiating chemotherapy. Baseline vaccination rates (March 2019) for pneumococcal pneumonia and influenza at our tertiary cancer centre were 8% and 40%, respectively. The aim of this study was to increase the number of gynecologic chemotherapy patients receiving pneumococcal and influenza vaccinations to 80% by March 2020. MethodsWe performed an interrupted time series study using structured quality improvement methodology. Three interventions were introduced to address vaccination barriers: an in-house vaccination program, a staff education campaign, and a patient care bundle (pre-printed prescription, information brochure, vaccine record booklet). Process and outcome data were collected by patient survey and pharmacy audit and analyzed on statistical process control charts. ResultsWe identified 195 eligible patients. Pneumococcal and influenza vaccination rates rose significantly from 5% to a monthly mean of 61% and from 36% to a monthly mean of 67%, respectively. The 80% target was reached for both vaccines during one or more months of study. The in-house vaccination and staff education programs were major contributors to the improvement, whereas the information brochure and record booklet were minor contributors. ConclusionsThree interventions to promote pneumococcal and influenza vaccination among chemotherapy patients resulted in significantly improved vaccination rates. Lessons learned about promoting vaccine uptake may be generalizable to different populations and vaccine types. In response to the global COVID-19 pandemic, initiatives to expand the program to all chemotherapy patients at our centre are underway.

Impact of intra-operative factors upon peri-operative outcomes in women undergoing hyperthermic intraperitoneal chemotherapy for gynecologic cancer

ObjectivesTo evaluate the incidence of intra-operative metabolic and electrolyte abnormalities and subsequent impact on peri-operative outcomes in women with gynecologic cancer undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS + HIPEC). MethodsAn IRB-approved single institution retrospective cohort study was performed in women with gynecologic cancer who underwent CRS + HIPEC. Patient demographics, intra-operative electrolyte and metabolic values and peri-operative outcomes were recorded. To assess the association of pH and lactate upon post-operative outcomes, patients were divided in four quartiles for both variables and univariate analysis was performed. Results100 consecutive women who underwent CRS + HIPEC from 2017 to 2020 were identified. Intra-operative blood transfusion and pressor support were required in 40% and 86%, respectively. The rate of ICU admission was 17%. Longer operative time (7.0 vs. 5.3 h, p = 0.002), increased blood loss (400.0 vs. 200.0 mL, p = 0.02) and transfusion (70.6% vs. 34.1%, p = 0.005) were associated with ICU admission. Compared to patients in the highest quartile of pH, lower median pH, (7.211 vs. 7.349, p < 0.001) was associated with increased rates of ICU admission, prolonged intubation (36.0% vs. 0.0%, p < 0.05, respectively) and any post-operative complication (72.0% vs. 28.0%, p = 0.01). Similarly, need for prolonged intubation (40% vs. 0%, p = 0.04) and VTE (13.0% vs. 0%, p = 0.01) were increased in women with the highest quartile of lactate levels compared to the lowest (4.7 vs 1.9, p < 0.001). ConclusionsIntra-operative acidosis is associated with higher incidence of ICU admission and peri-operative complications following CRS + HIPEC in women with gynecologic cancer. These data support the importance of adequate intra-operative resuscitation and timely correction of hemodynamic and metabolic abnormalities.

Sexual health and function among patients undergoing chemotherapy for primary gynecologic cancers

Objective: Impaired sexual function has been widely reported after cancer treatment, primarily in ovarian cancer, but few studies have examined sexual function during chemotherapy for all gynecologic cancers. Our primary objective was to compare sexual function during chemotherapy between women with primary versus recurrent disease.

Inpatient chemotherapy for gynecologic cancer: When is it worth it?

Objective: The aim of this study was to assess outcomes of gynecologic cancer patients who received inpatient chemotherapy and to assess the impact of diminished ability to complete activities of daily living (ADLs) using the Katz score.

Incidence and clinical course of septic shock in neutropenic patients during chemotherapy for gynecological cancers.

ObjectiveTo identify the incidence and clinical course of septic shock combined with neutropenia during chemotherapy in gynecological cancer patients.MethodsWe retrospectively reviewed the medical records of all gynecological cancer patients who received intravenous chemotherapy between March 2009 and March 2018. Patients diagnosed with neutropenic septic shock (NSS) during the course of chemotherapy were identified. We calculated the overall incidence and mortality rate of NSS, and analyzed risk factors and clinical course.ResultsA total of 1,009 patients received 10,239 cycles of chemotherapy during the study period. Among these, 30 (3.0%) patients had 32 NSS events, of which 12 (1.2%) died. With respect to patient age during the first course of chemotherapy, the incidence of NSS after the age of 50 was significantly higher than that in patients under 50 (3.9% vs. 1.4%, p=0.034). As the number of chemotherapy courses increased, the incidence of NSS increased, and linear-by-linear association analysis showed a positive correlation (p=0.004). NSS events occurred on average 7.8 days after the last cycle of chemotherapy, and the median duration of vasopressor administration was 23.3 hours. The median age (64.0 vs. 56.5, p=0.017) and peak heart rate (149.5 min−1 vs. 123.5 min−1, p=0.015) were significantly higher in the group of patients who subsequently died of NSS than in those who survived.ConclusionThe overall incidence of NSS in gynecological cancer patients receiving chemotherapy was 3.0%, which is higher than previously estimated. Peak heart rate during NSS events may be an indicator for predicting survival.

Phase I trial of selenium plus chemotherapy in gynecologic cancers

PurposePreclinical studies performed in our laboratory have shown that high-dose selenium inhibits the development of carboplatin drug resistance in an ovarian cancer mouse xenograft model. Based on these data, as well as the potential serious toxicities of supranutritional doses of selenium, a phase I trial of a combination of selenium/carboplatin/paclitaxel was designed to determine the maximum tolerated dose, safety, and effects of selenium on carboplatin pharmacokinetics in the treatment of chemo-naive women with gynecologic cancers. Correlative studies were performed to identify gene targets of selenium. MethodsChemo-naïve patients with gynecologic malignancy received selenious acid IV on day 1 followed by carboplatin IV and paclitaxel IV on day 3. A standard 3 + 3 dose-escalating design was used for addition of selenium to standard dose chemotherapy. Concentrations of selenium in plasma and carboplatin in plasma ultrafiltrate were analyzed. ResultsForty-five patients were enrolled and 291 treatment cycles were administered. Selenium was administered as selenious acid to 9 cohorts of patients with selenium doses ranging from 50 μg to 5000 μg. Grade 3/4 toxicities included neutropenia (66.7%), febrile neutropenia (2.2%), pain (20.0%), infection (13.3%), neurologic (11.1%), and pulmonary adverse effects (11.1%). The maximum tolerated dose of selenium was not reached. Selenium had no effect on carboplatin pharmacokinetics. Correlative studies showed post-treatment downregulation of RAD51AP1, a protein involved in DNA repair, in both cancer cell lines and patient tumors. ConclusionOverall, the addition of selenium to carboplatin/paclitaxel chemotherapy is safe and well tolerated, and does not alter carboplatin pharmacokinetics. A 5000 μg dose of elemental selenium as selenious acid is suggested as the dose to be evaluated in a phase II trial.

Abstract CT025: Phase I trial of selenium plus chemotherapy in gynecologic cancers

Abstract PURPOSE: The effectiveness of standard-of-care platinum-taxane chemotherapy in the treatment of patients with advanced gynecologic cancers is limited by the development of chemotherapy resistance in nearly all patients. Based on our preclinical findings that selenium, an essential trace element, inhibits the development of carboplatin drug resistance in an ovarian cancer mouse model, a phase I trial of a combination of selenious acid/carboplatin/paclitaxel was designed to determine the maximum tolerated dose (MTD) and safety of selenium administered with chemotherapy in chemo-naïve women with gynecologic cancers. In addition, the effects of selenium on carboplatin pharmacokinetics were evaluated in this group of patients, and correlative studies were performed to identify potential gene targets of selenium. METHODS: Patients with gynecologic malignancy not previously treated with chemotherapy received 50-5000 µg elemental selenium IV in the form of selenious acid on day 1 followed by carboplatin (cycle 1, AUC 5; subsequent cycles, AUC 6) IV and paclitaxel 175mg/m2 IV on day 3. A standard 3+3 trial design was used in the selenium dose escalation phase. Concentrations of selenium in plasma and carboplatin in plasma ultrafiltrate were analyzed. RNA expression in tumor specimens and breast and ovarian cancer cell lines were compared before and after treatment with selenium plus chemotherapy using the Human Exon 1.0 ST exon microarray platform. In addition, Western immunoblotting was performed to evaluate protein expression of RAD51AP1, a protein involved in DNA repair, in untreated MCF-7/Adr cells and MCF-7/Adr cells treated with selenium, carboplatin, and the combination of selenium and chemotherapy. RESULTS: Forty-five patients were enrolled and a total of 291 treatment cycles were administered. Grade 3/4 toxicities included neutropenia (66.6%), febrile neutropenia (2.2%), as well as pain (20.0%), infection (13.3%), neurologic (11.1%), and pulmonary adverse effects (11.1%). The MTD of elemental selenium was not reached. Selenium had no effect on carboplatin pharmacokinetics. In the subset of patients with stage III/IV ovarian cancer/fallopian tube/peritoneal cancer, median progression-free survival was 15 months; in those patients within this subset with measurable disease, 30%, 35%, and 23% experienced complete response, partial response, and stable disease, respectively. Correlative studies showed downregulation of RAD51AP1 by selenium plus chemotherapy in cancer cell lines as well as in tumors of patients treated within this clinical trial. CONCLUSION: Selenium in combination with carboplatin and paclitaxel is safe and does not affect carboplatin pharmacokinetics. It is possible that selenium-mediated downregulation of RAD51AP1 plays a role in circumventing the development of resistance to carboplatin/paclitaxel chemotherapy. A phase II study to further investigate these findings is underway. Citation Format: Mihae Song, Muthu N. Kumaran, Murugesan Gounder, Darlene Gibbon, Wilberto Nieves-Neira, Ami Vaidya, Mira Hellman, Michael P. Kane, Brian Buckley, Lorna Rodriguez-Rust. Phase I trial of selenium plus chemotherapy in gynecologic cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr CT025.

Multivariate analysis of risk factors for cisplatin-induced nephrotoxicity in gynecological cancer.

Risk factors for cisplatin-induced nephrotoxicity (CIN) vary by population. This study aimed to assess risk factors for CIN in patients with gynecological cancer. Patients who underwent cisplatin-based chemotherapy for gynecological cancer between January 2009 and December 2015 at Aichi Medical University School of Medicine were included in this study. CIN was defined according to the 'risk, injury, failure, loss, and end-stage kidney disease' (RIFLE) criteria and classified as either risk (Class R) or injury (Class I). Analyses were performed using univariate and multivariate logistic regression models. Among 112 patients enrolled, 30 had CIN. Multivariate analysis revealed that hydration with magnesium (odds ratio [OR], 0.223), history of cisplatin use (OR, 4.420), and hypoalbuminemia (OR, 4.170) were risk factors for Class R, and that frequency of cisplatin administration (OR, 5.620) and hydration with magnesium (OR, 0.216) were risk factors for Class I. This study confirmed that hydration without magnesium, history of cisplatin use, frequency of cisplatin administration, and hypoalbuminemia are significant risk factors for CIN.