bluuebunny/crossref_metadata_2025 huggingface dataset:
The burden of long-term complications among adolescent and young adult cancer survivors: An international comparison of two large cohorts.
Authors: Hayek Samah , Libresco Gilad , Barda Noam , Chao Chun , Lanfang Xu , Cannavale Kimberly L. , Izraeli Shai , Armenian Saro
Published: June 2022

e24059

Background: There is a paucity of information on health outcomes of adolescent and young adult (AYA) cancer survivors outside of Northern Europe or North America. We compared long-term health outcomes of Israeli AYA cancer survivors to non-cancer individuals with similar demographics and access to healthcare, estimated the risk of developing chronic health conditions by cancer type, and compared the comorbidity burden in Israeli AYA survivors to AYA cancer survivors from the U.S. Methods: This was a retrospective cohort of 2-year cancer survivors diagnosed with invasive cancer between 15 to 39 years of age from 2000 to 2018 in Clalit Health Services (CHS), the largest payer-provider healthcare organization in Israel. Non-cancer CHS participants were matched 4:1 to cancer survivors on age, sex, ethnicity, and membership duration. Health conditions were limited to those requiring medical intervention. Incidence rates for health conditions were determined for the two cohorts, and Poisson regression was used to determine the incidence rate ratio (IRR) with associated 95% confidence intervals (CI). A sub-population of CHS AYA survivors was used to compare the incidence of chronic health conditions from the Israeli cohort to AYA cancer survivors from Kaiser Permanente Southern California (KPSC), using Standardized Incidence Rate (SIR). Results: There were 12,674 CHS AYA cancer survivors and 50,696 non-cancer participants. Among survivors, the mean age at diagnosis was 31.02 years (SD: 6.2), 61.7% were female, and 78.4% were Jewish. The most common cancer diagnoses were lymphoma (16.5%), breast (16.4%), and thyroid (14.0%). Cancer survivors were significantly more likely to have any (IRR 1.60 95%CI: 1.54-1.67) or multiple (IRR 1.82 95%CI: 1.72-1.94) chronic health conditions compared to non-cancer participants. Survivors had an increased risk across nearly all examined outcomes, with an especially higher risk for premature ovarian failure (IRR 6.02 95%CI: 2.14-16.91), osteoporosis (IRR 4.74 95%CI: 4.06-5.53), and cardiomyopathy (IRR 4.20 95%CI: 3.35-5.27). We also found clear differences in the risk of specific health conditions by cancer type. Compared to the KPSC cohort, CHS cancer survivors had an overall lower (SIR 0.82 95%CI: 0.79-0.84) incidence of developing any health condition, with noticeably lower incidences of hypertension, hyperlipidemia, chronic liver disease, but higher incidences of cardiopulmonary diseases and osteoporosis. Conclusions: AYA cancer survivors in Israel are at increased risk for developing chronic conditions, compared matched non-cancer individuals, but the overall incidence of was lower when compared to survivors living in the U.S. These findings may allow for refinement of surveillance recommendations for AYA survivors, taking into consideration regional differences in socio-demographics and cancer care.
Efficacy, safety and cost effectiveness of reduced-dose olanzapine versus aprepitant as a part of triple-antiemetic therapy in the prevention of chemotherapy induced nausea and vomiting.
Authors: Mohammed Owais , Thota Narender kumar
Published: June 2022

e24078

Background: In Developing world, Olanzapine at a dose of 10mg is associated with excessive somnolence. Recently, reduced dose Olanzapine 5mg has been found to be equally effective with less sedation. Hence, we intended to conduct a study comparing the efficacy, safety, and cost effectiveness of reduced dose Olanzapine 5mg vs Aprepitant. Objectives: To compare Complete response (no emesis and no rescue therapy) rates between the two groups during three periods: 0 to 24 hours (acute), 25 to 120 hours (delayed), and 0 to 120 hours (overall) after chemotherapy. To compare nausea control rates in the acute, delayed, and overall periods. To evaluate potential adverse effects and compare cost effectiveness of Olanzapine, Aprepitant. Methods: All newly diagnosed cancer patients who were scheduled to receive highly emetogenic chemotherapy (either cisplatin at a dose ≥70 mg/ m2 body surface area, with or without other chemotherapeutic agents, or doxorubicin at a dose of 60 mg/m2 plus cyclophosphamide at a dose of 600 mg /m2) and had a European Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 were randomized 1:1 to receive triple anti emetic regimen comprising of 5HT3 antagonist (Palonosetron)+Steroid (Dexamethasone) + either NK1 antagonist (either Aprepitant 125mg on day 1, 80 mg on days 2, 3 or Fosapprepitant 150mg IV on day 1) or Olanzapine 5mg once daily on days 1-4). Number of Vomiting episodes, use of rescue therapy, nausea, other adverse effects were recorded. Results: A total of 154 patients were eligible for the study, 77 in each arm. The Complete response rates for Aprepitant and Olanzapine during the acute period were 79.22% and 81.81% respectively (p > 0.05), during the delayed period were 74.02% and 70.12% respectively (p > 0.05), during the overall period were 74.02% and 70.12% respectively (p > 0.05). Nausea control rates for Aprepitant and Olanzapine during the acute period were 74.42% and 84.82% respectively (p > 0.05), during the delayed period were 45.45% and 68.83% respectively (p < 0.05), during the overall period were 45.45% and 68.83% respectively (p < 0.05). Most common side effect in patients receiving Olanzapine was Somnolence which was observed in 12.98% patients (CTCAE Grade 2). Most common side effect in patients receiving Aprepitant was fatigue which was seen in 6.5% patients. A 4-day course of Olanzapine costs INR-20/- while a 3-day course of Aprepitant costs INR-1000/- and a single 150mg IV Fosapprepitant costs INR 2500/-. Conclusions: In the developing world, Olanzapine 5mg can be considered as an effective, safe, and a cheaper alternate to Aprepitant as a component of triple antiemetic regimen in the prevention of nausea and vomiting in patients receiving highly emetogenic chemotherapy.
Evaluation of cross-disciplinary educational material to improve patients’ knowledge and utilization of palliative radiation therapy.
Authors: Rizvi Faryal , Young Meredith , Habib Muhammad Hamza Hamza , Kra Joshua , Shah Ankit , Mayer Tina M. , Saraiya Biren , Mattes Malcolm David
Published: June 2022

e24082

Background: Palliative radiation therapy (PRT) is underutilized in the United States, in part due to misconceptions among patients and other providers about its risks, benefits, and indications. Empowered patients, who are more knowledgeable about how radiation can alleviate cancer-induced symptoms, may facilitate more appropriate and timely use of PRT. In this pilot study patient-directed educational material describing PRT was developed and used among patients being treated in medical oncology and palliative care clinics. The hypothesis is that most patients will gain new knowledge from educational content about PRT, and perceive it as useful in their care. Materials/Methods: A 1-page educational handout was developed to convey general information about the purpose, logistics, benefits, risks, and common indications for PRT. Patients undergoing treatment for a metastatic solid tumor were invited to participate during their regular clinic visit. Patients who chose to participate read the handout, and then completed a multiple choice questionnaire assessing how much they learned from the handout (nothing vs. little vs. lots), whether the information in the handout was useful (no vs. somewhat vs. very), as well as other questions. Responses were anonymous. There was no follow-up with participants. Descriptive statistics are reported, with Fisher’s Exact Test used to compare subgroups of patients. Results: A total of 70 patients from 1 palliative care physician and 4 medical oncologists participated between June – December 2021. Sixty-five patients (89%) felt they learned from the handout (38% learned “lots”) and 69 (94.5%) felt the information was useful (53% “very useful”). Twenty-one patients (28.8%) learned that PRT can help with symptom relief, 55 (75%) learned that PRT can be delivered in a course of 5 treatments or less, and 43 patients (59%) learned that PRT usually has few side effects. Furthermore, 16 (22%) felt they currently had symptoms not being treated well enough, and 34 (47%) felt they currently had symptoms that radiation might help with. Most patients felt more comfortable bringing symptoms to a medical oncologist’s (n = 57, 78%) or radiation oncologist’s (n = 51, 70%) attention after reading the handout. Forty-one patients (56.2%) reported a prior visit with a radiation oncologist, but this did not impact their responses related to learning from the handout ( p< 0.001) or finding the handout useful ( p< 0.001). Conclusions: Patient-directed educational material about PRT provided outside of a radiation oncology department was perceived by patients as improving their knowledge, and adding value in their care, independent of their prior exposure to a radiation oncologist. Further research will evaluate the impact of the educational material on referral patterns.
Shortening the baseline period in hot flash symptom control trials: Comparison of a one-day versus seven-day baseline hot flash diary.
Authors: Childs Daniel S , Novotny Paul J. , Marrell Paulina S , Ruddy Kathryn Jean , Loprinzi Charles L.
Published: June 2022

e24094

Background: Hundreds, if not thousands, of participants are enrolled hot flash trials each year given the magnitude of the problem for breast and prostate cancer survivors. Classically, these studies have included a baseline period of 1-week, or longer, to understand the frequency and severity of hot flashes before starting a new treatment. The objective of the current study was to compare the accuracy of a 1-day baseline hot flash diary to a more traditional 1-week dairy. A shorter baseline period would be more convenient for patients and provide a more efficient study design. Methods: Raw data from 5 pilot studies and 15 phase III randomized, controlled trials (RCTs), all of which used a one-week baseline period, were obtained. Descriptive statistics were used to describe day-by-day variations in hot flash frequencies and scores, during the baseline week. Additional analyses evaluated whether the conclusions from any of the individual pilot studies would have been changed if only a 1-day baseline period had been used. For the RCTs, p-values were recalculated using mixed models, adjusting for the baseline value by including it as a covariate. Results: A total of 2,573 participants were included. On average, participants had 8.5 hot flashes per day on Day 1. Mean hot flash frequencies and scores on subsequent days (Days 2-7) were within 6% of Day 1 values. When comparing a 1-day to a 1-week baseline period, there was an absolute difference of only 0.29 hot flashes per day (SD 2.25). Re-analysis for each pilot study revealed that no individual study conclusions would have been meaningfully altered by a shorter baseline. For the RCTs, a shorter baseline period changed the results of only 1 of 24 comparisons from statistically significant to not significant, or vice versa. Conclusions: A 1-day hot flash diary appears to accurately reflect true frequency and severity of baseline hot flash symptoms in appropriately sized cohorts. Results support a shorter baseline period for pilot studies and RCTs.
Shifting perceptions of alternative therapies in cancer patients during the COVID-19 pandemic: Results from the Complementary and Alternative Medicine Exposure in Oncology (CAMEO) Study.
Authors: Weil Christopher R. , Hutten Ryan J. , Barney Brandon M. , Fagerlin Angela , Gaffney David K. , Gill David Michael , Whipple Gary , Rhodes Terence Duane , Scherer Laura , Suneja Gita , Tward Jonathan David , Werner Theresa Louise , Johnson Skyler B , Evans Jaden D.
Published: June 2022

e24130

Background: Complementary and alternative medicine (CAM) use has been associated with worse survival outcomes in cancer patients compared to standard of care therapies. CAM has received a significant increase in public awareness and interest in the COVID-19 pandemic era. We sought to understand how the COVID-19 pandemic affected CAM use and perceptions in cancer patients. Methods: Data was collected from adult cancer patients prospectively enrolled on a cross-sectional survey conducted at an NCI-designated cancer center and a comprehensive cancer center between 2020 and 2021. The survey included questions assessing changes in patient attitude towards CAM and likelihood of using CAM, both relative to prior to COVID-19. Analyzed CAM users included those taking vitamin, mineral and herbal supplements, alternative medicines and special diets, and excluded mind-body practices as the focus of this analysis was on enteral and parenteral CAM therapies. Differences in the impact of COVID-19 on CAM use beliefs and practices between CAM users and non-users were analyzed with χ2 and two-sample t-tests. Results: Out of 749 respondents, 578 (77%) used any CAM and 470 (63%) used enteral or parenteral CAM. Results shown in table. Compared to prior to COVID-19, CAM users were more likely to view CAM more favorably (12% vs 5%, p < 0.01), while non-users were more likely to have an unchanged opinion (90% vs 84%, p = 0.03). Females had higher rates of viewing CAM more favorably than males (80% vs 58%, p = 0.04). Patients who viewed CAM more favorably had higher rates of self-reported incurable cancer (36% vs 11%, p = 0.04), declining recommended hormone therapy (22% vs 0%, p < 0.01), and higher trust of social media (19% vs 0%, p = 0.02) and websites (24% vs 0%, p < 0.01). Since the start of COVID-19, CAM users were more likely to report increased likelihood of using CAM (12% vs 6%, p = 0.01). Patients who were more likely to use CAM had higher rates of declining recommended chemotherapy (12% vs 0%, p = 0.02), and higher trust of social media (15% vs 2%, p = 0.01) and websites (28% vs 7%, p < 0.01). Conclusions: During the COVID-19 pandemic, attitudes on CAM use in oncology patients have become increasingly polarizing. Patients with favorable attitudes toward CAM were likely to decline recommended standard of care therapy and more like to use CAM since COVID-19. This data helps characterize shifting attitudes toward CAM and may help guide shared decision-making between physician and patient.[Table: see text]
Perceived risk of breast cancer and god health locus of control in high risk African American and caucasian women.
Authors: Nguyen Minh-Tri , Thompson Cheryl L. , Knight Joy
Published: June 2022

e24142

Background: African American women are more likely than any other racial groups to present with a later stage of breast cancer. Survival rates among African American women with breast cancer are lower than that of their Caucasian counterparts. Studies have shown that women who believe that they can control their health through their own behavior may be more likely to report a lower perceived risk that women who believe that others (such as God or “powerful others” or chance) control their health outcomes. There is a limited body of literature on the effects of spiritual locus of health control and a patient’s perceived risk of breast cancer. Herein, we studied the association between God Locus of Health Control (GLHC) and perceived risk of breast cancer among 85 women recruited from a high-risk clinic. Methods: Consented participants that agreed to the study were asked to fill out the Patient Reported Outcomes Measurement Information Systems (PROMIS) initiative questionnaire. The PROMIS initiative standardizes measurements of psychosocial research in cancer to address major shortcomings in this field. The questionnaire includes demographic characteristics, perceived risk of breast cancer, and questions regarding spiritual and GLHC. Differences in patient demographics (including race), perceived risk, and multivariate testing was performed. Results: When asked to rank their chances of developing breast cancer in their lifetime, Caucasian participants were statistically more likely to respond with a higher perceived risk than African American participants (p = 0.01). Caucasian participants were more likely to respond with a higher perceived risk score when asked to compare their chances of developing breast cancer to that of the average woman their age (p = < 0.001). Linear regressions correlating perceived risk, degree of GLHC and race did not show any statistical significance. Multivariate analyses only showed race was a statistically significant predictor of any of the perceived risk variables. Our study showed that Caucasian participants were more likely to have a lower GLHC score than their African American counterparts and were more likely to perceive a higher risk of developing breast cancer. GLHC was not statistically significantly associated with any of the 4 perceived risk measures (p > 0.05 for all). Conclusions: Overall, there was not a statistically significant relationship between GLHC scores and perceived risk. Further larger-scale studies will be needed to further characterize these findings.
Trial in progress: A phase I trial of dual EZH 1/2 inhibitor valemetostat tosylate (DS-3201b) in pediatric, adolescent, and young adult patients with malignant solid tumors.
Authors: Arakawa Ayumu , Ozawa Hitoshi , Hirakawa Akihiro , Sadachi Ryo , Hoshina Yukari , Tomatsuri Sawako , Saito Yoshimasa , Ando Reiko Makihara , Terashima Keita , Nakamura Kenichi , Ogawa Chitose
Published: June 2022

TPS10059

Background: Enhancer of zeste homolog enzymes (EZH1 and EZH2) form parts of the polycomb repressive complex 2 and regulate gene expression by catalyzing the tri-methylation of lysine 27 residue of histone H3. SMARCB1/INI1 is one of the core components of the SWI/SNF chromatin remodeling complex, with the loss of SMARCB1/INI1 causing the oncogenic activation of EZH2 and EZH1. The inhibition of EZH2 or both EZH2 and EZH1 can be effective against various hematological malignancies and SMARCB1/INI1-deficient solid tumors. Valemetostat tosylate (DS-3201b; valemetostat) is a potential first-in-class dual inhibitor of EZH1 and EZH2 that targets epigenetic regulations by inhibiting both EZH1 and EZH2 enzymes. A phase 2 single-arm study showed that valemetostat demonstrated promising response rates in Japanese patients with relapsed or refractory adult T-cell leukemia/lymphoma (Yoshimitsu M et al., presented at ASH Annual Meeting, 2021). Tumors characterized by SMARCB1/INI1 deficiency (a SWI/SNF mutation), such as malignant rhabdoid tumors, epithelioid sarcoma, or synovial sarcoma are quite frequently observed during childhood and adolescence, among whom valemetostat is expected to show antitumor effects. Methods: This open-label multi-center phase I trial evaluates the safety and efficacy of valemetostat in pediatric, adolescent, and young adult patients with refractory/relapsed solid tumors. The inclusion criteria are relapsed, refractory, or progressive metastatic disease; >3 and <19 years of age during the dose escalation cohort and < 29 years of age in the expanded cohort; performance status of >50 (assessed by Karnofsky Performance score in patients >16 years old, and Lansky Performance score in patients <15 years old); and adequate organ function. Valemetostat is administered orally once a day without interruption. Three dose levels (150, 200, and 250 mg/1.7 m2) are assessed using a 3+3 design during the dose escalation cohort. After determining the recommended phase 2 dose (RP2D) during dose escalation cohort, up to 30 patients will be further enrolled, and the safety and efficacy data of valemetostat are determined in the expanded cohort. The primary endpoint is the incidence of dose limiting toxicity, whereas the secondary endpoints include safety, pharmacokinetics, overall response rate, progression-free survival. The overall response rate of the tumors with SMARCB1/INI1 deficiency or SWI/SNF mutation is also evaluated as a secondary endpoint. Exploratory endpoint includes overall survival. Enrollment into this trial began in March 2020, and enrollment into the dose escalation cohort was completed. Enrollment into the expanded cohort began in November 2021. Clinical Trial Information: jRCT2031190268.
A multicenter, open-label, phase 2 study of odetiglucan (IMPRIME PGG) and pembrolizumab in patients with metastatic breast cancer (mBCA) who have progressed through prior hormonal therapy.
Authors: Stopeck Alison , Gargano Michele Anne , Niles Nick , Rathmann Blaine , Chisamore Michael Jon , Bose Nandita , Iglesias Jose Luis
Published: June 2022

TPS1115

Background: Hormone receptor (HR) positive/ human epidermal growth factor receptor 2-negative (Her2-) breast cancer is generally considered ‘immunologically cold’ in comparison to TNBC or Her2+ breast cancer. Keynote-028 results showed a modest ORR of 12% to anti-PD1 antibody, pembrolizumab (PEM) in previously treated HR+/ HER2-/programmed death ligand 1-positive (PD-L1-positive) advanced breast cancer patients (pts). With limited options available, there is significant unmet need to expand clinical benefit from ICI. Odetiglucan, a novel beta glucan, acts as a pathogen-associated molecular pattern (PAMP) that drives a cascade of immune activating events. It repolarizes the immunosuppressive microenvironment, activates the maturation of antigen presenting cells and significantly enhances efficacy of ICI therapy in preclinical tumor models. In a Ph2 trial (IMPRIME 1) of odetiglucan + PEM in 44 pts with heavily pretreated metastatic TNBC, an ORR=15.9%, DCR=54.5%, mDOR=12.7mo, mPFS=2.86 mo, 12 mo OS rate=57.6%, and mOS=16.4 mo were observed. Clinical benefit was particularly evident in a subset of pts, mTNBC “converters” (12/44 pts) who were originally diagnosed with ER/PR+ disease and progressed through endocrine therapies +/- CDK4/6 inhibitors. In these 12 pts, an ORR=50%, DCR=83%, mDOR=11.2, mPFS=5.6 mo, 12-mo OS rate=64.8%, and mOS=17.4 mo were observed. Methods: Odetiglucan + PEM is now being explored in pts with hormone-resistant metastatic breast cancer (MBC). This is a phase 2, Simon’s 2-Stage study of MBC pts who have progressed through prior hormonal therapy with >1 CDK4/6 inhibitor. Pts will receive odetiglucan 4 mg/kg/wk + PEM 200 mg Q3wk. Stage 1 will enroll 23 pts. If >4 pts have an objective response after 12 wks of treatment, the study will proceed to Stage 2 enrolling an additional 24 pts (N=47). Rejection of the null hypothesis requires >10 objective responses. Main eligibility criteria include: MBC having failed prior hormonal therapy with >1 CDK4/6 inhibitor, <2 chemotherapies, serum ABA ≥20 µg/mL, and no prior ICI exposure. Primary endpoint is ORR (RECIST v1.1); secondary endpoints are PFS, OS, DCR, DoR, and safety. Exploratory objectives assess impact of the treatment combination on immune activating events in peripheral blood and tumor biopsies, and correlate tumor microenvironmental changes with clinical benefit Select subpopulations may be explored. Point estimates with 95% confidence intervals (CIs) of ORR and DCR will be computed. Medians, first, and third quartiles with 95% CI will be estimated using Kaplan-Meier method for other secondary endpoints. Safety parameters will be summarized. The trial is sponsored by HiberCell, Inc. in collaboration with Merck & Co. ̃25 US sites will participate. Clinical trial information: NCT05159778.
Phase 1b/2 study of ladiratuzumab vedotin (LV) in combination with pembrolizumab for first-line treatment of triple-negative breast cancer (SGNLVA-002, trial in progress).
Authors: Meisel Jane Lowe , Pluard Timothy J. , Vinayak Shaveta , Stringer-Reasor Erica Michelle , Brown-Glaberman Ursa , Dillon Patrick Michael , Basho Reva K , Varadarajan Ramya , O'Shaughnessy Joyce , Han Hyo S. , Sinha Rajni , Fox Jenny R. , Villanueva Rafael , Chen Lin Chi , Wu Sheng , Li Hong , Tran Sinhan , Manso Luis
Published: June 2022

TPS1127

Background: Patients with metastatic triple-negative breast cancer (mTNBC) have a poor prognosis. Treatment combinations of anti-programmed death ligand 1 (anti–PD-L1) agents with chemotherapy have shown promise in mTNBC. LV is an investigational antibody–drug conjugate directed to LIV-1, a protein highly expressed on breast cancer cells, via a humanized IgG1 monoclonal antibody conjugated to monomethyl auristatin E (MMAE) by a protease-cleavable linker. LIV-1–mediated delivery of MMAE disrupts microtubules and induces cell cycle arrest and apoptosis. LV has also been shown to drive immunogenic cell death (ICD) to elicit an immune response. LV + pembrolizumab may result in synergistic activity through LV-induced ICD, creating a microenvironment favorable for enhanced anti–PD-L1 activity. Preliminary results show LV delivered once every 3 weeks (Q3W) + pembrolizumab was tolerable with encouraging antitumor activity in patients with mTNBC (Han 2019). Additionally, interim results of weekly LV monotherapy at doses up to 1.5 mg/kg were clinically active and generally well tolerated (Tsai 2021). Based on pharmacokinetic and pharmacodynamic modeling and simulation analysis, an intermittent LV + pembrolizumab dosing regimen is being evaluated to further enhance efficacy and improve the tolerability profile. Due to an unmet medical need for patients with mTNBC who are PD-L1 low or negative, Part D will focus on this patient population. Methods: SGNLVA-002 (NCT03310957) is an ongoing global single-arm, open-label phase 1b/2 study of LV + pembrolizumab as 1L therapy for patients with unresectable locally advanced/mTNBC. Part D is currently enrolling ̃40 patients. Eligible patients must have advanced disease with no prior cytotoxic/anti–PD-L1 treatment, PD-L1 combined positive score < 10, measurable disease per RECIST v1.1 and an ECOG score ≤1. Patients with Grade ≥2 pre-existing neuropathy or active central nervous system metastases are not permitted. Patients will receive LV at 1.5 mg/kg on Days 1 and 8 plus pembrolizumab 200 mg on Day 1 Q3W. The primary objectives are to evaluate the safety/tolerability and objective response rate of LV + pembrolizumab. Secondary objectives include duration of response, disease control rate, progression-free survival, and overall survival. Safety and efficacy endpoints will be summarized with descriptive statistics. Global enrollment is ongoing in the US, EU, and Asia. Clinical trial information: NCT03310957.
Take charge during treatment: A planned exercise protocol to evaluate disparities and cardiovascular outcomes in Black and White patients with breast cancer undergoing treatment.
Authors: Hidde Mary , Beyer Andreas M , Beyer Kirsten M. M. , Durand Matthew J , Phillips Shane A , Grigoriadis Georgios , Jankowski Courtney , Berendt Madeline , Canales Bethany , Norwood Toro Laura , Kong Amanda L. , Hoskins Kent , Brown Sherry-Ann , Gutterman David , Stolley Melinda
Published: June 2022

TPS12138

Background : Cardiotoxicity is a significant challenge associated with common first-line breast cancer (BC) chemotherapy (CTx) treatments including anthracyclines (AC) and targeted therapies, such as anti-Her-2 therapy. For targeted therapies, cardiac complications typically resolve once treatment is completed or stopped. For ACs, treatment may lead to permanent long term cardiac damage, and elevated risk for major adverse cardiovascular events (MACE). Black/African American (B/AA) women are at higher risk for AC-based cardiotoxicity compared to Non-Hispanic White (NHW) women. To date, most efforts have targeted managing and defining mechanisms of large vessels and cardiac damage. However, impaired microvascular function, a powerful but clinically underused predictor of future MACE, may also be implicated. Extensive evidence shows that exercise interventions reduce systemic inflammation and possibly MACE. However, few cardio-oncology studies have utilized exercise to mitigate cardiotoxicity, and none have quantified microvascular endothelial function. A further gap in cardio-oncology research is a paucity of studies focused on understanding and addressing disparities. This research project aims to 1) test the feasibility and efficacy of an exercise intervention designed to mitigate the effects of CTx, Take Charge during Treatment (TCT) and 2) examine the influence of socio-ecological factors on endothelial function in response to an exercise intervention. Methods: B/AA (n=50) and NHW (n=50) women diagnosed with non-metastatic BC, scheduled to receive AC and/or anti-HER-2 therapy, will be recruited and randomized to participate in the TCT intervention or usual care (NCT05223322). TCT is a virtual exercise coaching program with weekly coaching sessions, six of which include supervised exercise. Assessments to assess socio-ecologic and vascular outcomes are presented in the Table. Assessments will be completed prior to treatment (T1), after treatment completion (18-24 weeks, T2), and 12-months post treatment (T3). Clinical trial information: NCT05223322. [Table: see text]
Episodic future thinking: A behavioral intervention to promote weight loss in breast cancer survivors.
Authors: Sukumar Jasmine S , Vaughn Jennifer , Stein Jeffrey , Schnell Patrick , Sudheendra Preeti Khetarpal , Pariser Ashley , Gatti-Mays Margaret Elena , Williams Nicole Olivia , Cherian Mathew Amprayil , Stover Daniel G. , Wesolowski Robert , Ramaswamy Bhuvaneswari , Lustberg Maryam B. , Sardesai Sagar D.
Published: June 2022

TPS12139

Background: Obesity at diagnosis is associated with an increase in breast cancer (BC) specific mortality. Behavioral interventions targeting obesity-related health choices offer a scalable approach to improve patient engagement in the community. Episodic Future Thinking (EFT) is a novel remotely delivered behavioral intervention which engages the science of prospection where participants mentally simulate positive, detailed, and personal events that can occur in the future. EFT targets a key behavioral economic measure – Delay Discounting (DD). As DD rate rises, an individual devalues future outcomes to a greater degree and has a higher bias for immediate gratification. EFT can decrease DD in obese patients, leading to improved diet quality and weight loss. However, valuation of the future may impact cancer survivors differently. Herein, we propose the first randomized Phase II trial evaluating adherence and changes in DD and body weight with 12-week remotely delivered EFT vs control in overweight or obese BC survivors. Methods: Eligible patients have a history of DCIS or stage 1 to 3 BC, BMI > 25 kg/m2, have completed surgery, radiation, and chemotherapy, and are motivated to lose weight. They are randomized 1:1 to a 12-week EFT intervention or control (Episodic Recent Thinking; ERT). ERT is a validated control in which patients imagine events in the recent past. Randomization will be stratified by baseline DD rate. There is an optional 12 week follow up period where patients can continue to receive EFT or ERT cues. DD will be measured at baseline and every 4 weeks for 24 weeks. The primary endpoint is adherence, measured by percentage of thrice daily smartphone prompts participants open and attend to during the 12-week trial. Secondary endpoints are changes in body weight and DD rate at 12 and 24 weeks and change in PROs (PROMIS scales), insulin resistance (HOMA-IR), hs-CRP, and diet quality (HEI 2015) at 12 weeks from baseline. With 20 subjects per arm, the study has 80% power to detect deviation of 14 points from a target adherence rate of 80% using a 1 sample t-test. The primary endpoint is evaluable for all subjects, regardless of drop-out. Secondary endpoints will be evaluated using a linear mixed effects model. Hypothesis tests and confidence intervals will be two-sided at 5% significance/95% confidence level. Since trial activation in November 2021, 9 of the planned 46 patients are enrolled. Accrual is closely integrated with the dedicated Ohio State University Comprehensive Cancer Center Survivorship Program. This work is supported by the Alliance Cancer Control Program Pilot Award (5UG1CA189823-08). Clinical trial information: NCT05012176.
Preventive effect of goshajinkigan against peripheral neuropathy induced by paclitaxel-containing chemotherapy: An open-label, randomized, phase II study.
Authors: Nakamura Naoki , Kato Yuka , Makimoto Go , Ninomiya Kiichiro , Harada Daijiro , Ninomiya Takashi , Oze Isao , Kubo Toshio , Fujii Masanori , Ichihara Eiki , Ohashi Kadoaki , Kozuki Toshiyuki , Hotta Katsuyuki , Tabata Masahiro , Kiura Katsuyuki
Published: June 2022

TPS12141

Background: Paclitaxel is a taxane agent that has been used as a standard treatment for various malignancies. However, taxanes, such as paclitaxel, unfortunately cause a high frequency of chemotherapy-induced peripheral neuropathy (CIPN) as a result of axonal damage (All grade; 70%) (Clin Cancer Res.1996), CIPN worsens patients’ QOL and then lead to poor treatment compliance. Furthermore, there is no evidence for the prevention of CIPN. Goshajinkigan (GJG) is one of the Kampo medicine and it is approved in Japan for the treatment of numbness and has been commonly used for diabetic peripheral neuropathy. In addition, a non-clinical study has also shown the preventive effect of GJG against CIPN induced by paclitaxel (Molecular pain. 2014). To investigate if GJG indeed has a preventive effect for severe CIPN in patients receiving chemotherapy including paclitaxel, we started a two-arm randomized trial of GJG vs physician’s choice of treatment for patients. Methods: Patients have to meet the followings: pathologically diagnosed with malignant tumor (regardless of cancer type) and scheduled to receive ≥4 courses of chemotherapy including carboplatin and paclitaxel (paclitaxel ≥150mg/m2 every 3-4 weeks) as initial chemotherapy; age ≥20yrs; Performance Status of 0 or 1. The primary endpoint is set as a proportion of ≥G2 CIPN by CTCAE ver.5.0 by the end of 4 courses of chemotherapy. With stratification by cancer type and age, patients will be randomized centrally to receive GJG at the same time as chemotherapy (A), or to receive the physician’s choice of treatment for pts if ≥G2 CIPN occurs without prophylaxis (B). Assuming that the incidence of ≥G2 CIPN would be 50% without prophylaxis and 20% with GJG prophylaxis, and assuming an 80% completion rate of four paclitaxel courses, the required sample size is 66 patients (1-β: 0.75, α: 0.1). The secondary endpoint includes time to the onset of CIPN G2, incidence rate and severity of CIPN at the end of each course, relative dose intensity of paclitaxel, adverse events other than CIPN. Enrollment began in 2022, and will be complete by 2025. Clinical trial information: 061210047.
Optimizing supportive care for patients with metastatic lung cancer in the era of precision oncology.
Authors: Hsu Kelly , Sequist Lecia V. , Jackson Vicki A. , Park Elyse R. , Rabideau Dustin , Greer Joseph A. , Temel Jennifer , Petrillo Laura A
Published: June 2022

TPS12150

Background: Targeted therapy improves survival for patients with oncogene-driven non-small cell lung cancer (NSCLC). However, metastatic NSCLC remains incurable and patients often experience uncertainty about what to expect from their long and unpredictable illness trajectories. The aim of this trial is to pilot test a supportive care intervention that blends palliative care and survivorship for patients with metastatic oncogene-driven NSCLC. Methods: We will conduct a pilot randomized, controlled trial to evaluate the feasibility, acceptability and preliminary efficacy of a novel supportive care intervention for patients with metastatic oncogene-drive NSCLC. We will enroll 90 patients with a recent (within 6 months) diagnosis of metastatic NSCLC with a mutation in EGFR, ALK, ROS1 or RET genes who are receiving targeted therapy. We will enroll the first ten patients in an open pilot and we will refine the intervention and study procedures based on pilot findings. We will randomize the remaining 80 patients 1:1 to the intervention or a usual care control. Participants randomized to the intervention arm will have four monthly visits with a palliative care clinician who has been trained to address the supportive care needs of patients with long illness trajectories. Sessions will cover 1) rapport building and baseline symptom and psychosocial assessment; 2) coping support and healthy lifestyle promotion; 3) cultivation of prognostic understanding; and 4) exploration of goals and values. Patients in both arms will complete surveys including secondary outcome measures at baseline, 12, and 20 weeks post-enrollment. The primary outcome of the study is feasibility of the palliative care intervention, defined as at least 60% enrollment among eligible patients and 75% completion of all four sessions and three surveys. We will also assess acceptability using measures of satisfaction and comfort with the intervention. We will evaluate the preliminary effects of this intervention on the following outcomes to inform a future large-scale efficacy trial: 1) distress related to prognostic uncertainty and 2) prognostic awareness (using the Prognostic Awareness Questionnaire: 34-item validated measure with items about likelihood of cure and impact of prognostic awareness on decisions, behaviors and mood); 3) confidence in chronic disease management using the Self-Efficacy of Management of Chronic Disease scale; and 4) documentation of discussions about goals and values in the medical record. We will analyze change within and between groups at 12 and 20 weeks using linear mixed models, controlling for baseline values and relevant demographic and clinical factors. Study accrual to the open pilot phase began in February 2022. Current enrollment: n = 0. Clinical trial information: NCT04900935.
Natural history study for children and adults with rare solid tumors.
Authors: Varghese Diana Grace , Smith Hannah , Ahmed Shadin , Thomas B. J. , Bernstein Donna , Raygada Margarita , Lockridge Robin , Glod John , Del Rivero Jaydira , Reilly Karlyne , Widemann Brigitte C. , Wedekind Malone Mary Frances
Published: June 2022

TPS1600

Background: Rare cancers is defined as fewer than 15 cases per 100,000 people per year and account for 27% cancers diagnosed and lead to 25% of cancer-related deaths. Nearly 13% (1 in 8) of all cancers diagnosed in adults ages 20 and older are rare. All pediatric cancers are rare and approximately 12,600 children under the age of 20 years are diagnosed with cancer each year. Rarity of these diseases has caused a stagnation in understanding the tumor biology and developing newer therapies. Initiatives like Orphan Drug Act (1983) and Rare Disease Act (2002) has led to improvement in funding and research about these rare tumors. The Cancer Moonshot Research Initiative funded My Pediatric and Adult Rare Tumor (MyPART) network (cancer.gov/mypart) in the NCI Pediatric Oncology Branch and launched a longitudinal Natural History Study for Children and Adults with Rare Solid Tumors (NCT03739827). Methods: A prospective study to evaluate the natural history of rare pediatric and adult solid tumors comprehensively and longitudinally. Patients of any age with a rare solid tumor (<15 cases per 100,000 people per year) are eligible. Patients with germline mutation who are at risk of developing these tumors or relatives of participants are also eligible. Patients can participate from home or are are invited to NIH for annual evaluations. Participants complete individual medical history, family history, patient related-outcomes measurements (PROs) and provide samples (blood, saliva) for DNA analysis. Tumors are analyzed using a 500+ gene panel (TruSight500, Illumina Panel) and undergo a comprehensive genomic and epigenomic analysis. Participants invited to NIH undergo a clinical evaluation, genetic counseling, blood collection (standard clinical labs, germline DNA/RNA, immune phenotypes, cytokines, exosomes), and imaging studies, as indicated. The goals of this study are to 1) Estimate and define the clinical spectrum of rare cancers 2) Evaluate and follow biological relatives of patients with rare tumors or carriers of germline genetic variants that predispose to development of rare tumors 3) Develop a better understanding of these diseases in an effort to develop a) Novel therapeutic interventions, b) Preventive/screening guidelines, c) Endpoints for future clinical trials, and d) Relevant patient reported outcomes that can improve our understanding of patients psychosocial and functional needs. Subprotocols under this protocol for children and adults include adrenocortical cancer (NCT04447014), neuroendocrine neoplasms (NCT04488263) and Chordoma (NCT0391046) to gather tumor specific data. Study accrual is ongoing. Clinical trial information: NCT03739827.
Telehealth weight loss program for breast cancer survivors is feasible and acceptable: Preliminary results of pilot clinical trial.
Authors: Tchou Julia C. ,   UPENN Authors' Group
Published: June 2022

TPS1603

Background: Current weight loss programs for breast cancer survivors utilize a hybrid of in-person visits or individualized telephone-based sessions modeled after the Diabetes Prevention Program. Telehealth may be an effective and efficient means of communicating with patients who otherwise cannot participate in in-person visits. To test this concept, we conducted a pilot single-arm study (NCT04855552) to examine the feasibility and acceptability of a weight loss group program via telehealth for breast cancer survivors. Methods: Patients > = 18 years with ECOG performance 0 or 1, a BMI of ³ 25 kg/m2, and completion of adjuvant radio- and/or chemo-therapy > 6 months were eligible. Patients attended weekly zoom teleconference counseling grouped sessions either at noon or 5 pm led by a licensed clinical psychologist for 20 weeks followed by sessions in weeks 22 and 24. Patients were encouraged to use MyFitnessPal.com, an online tool, to monitor calorie intake and physical activity and digital scales to monitor weight to share with study staff to enhance accountability and provide opportunity for feedback. Feasibility was defined as a ratio of enrolled/eligible patients ≥50%. Acceptability was assessed from surveys pre- and post-treatment, and qualitatively from exit interviews. Secondary endpoints included changes in Quality of Life-Breast Cancer Patient (QOF-BC), Patient Health Questionnaire (PHQ-9), and percent weight loss from baseline to 24 weeks. Results: Clinical characteristics of patients are summarized in Table. The ratio of enrolled (n = 12)/eligible (n = 23) participants was 52% thus confirming study feasibility. One patient dropped out after 2 sessions. Qualitative results from exit interviews showed that 7/9 patients rated the telehealth format as “extremely acceptable”. Surveys also indicated that the format and delivery of the program remained acceptable across most domains with no significant changes, except an increase in “approval” from 4.1 to 4.7 ( p= 0.05). Patients’ mood improved on the PHQ-9 from 4.2 to 1.2 (p = 0.03), and QOL-Physical Wellbeing improved from 56.9 to 66.3 (p = 0.004). Overall, 199 of 236 participant-sessions (84%) were attended. Percent weight loss was 6.5% +/- 2.5%. Conclusion: This proof-of-concept weight loss program was feasible and acceptable for our patients yielding improvements in QOL, mood, and a clinically significant weight loss over 6-months. This group-based video approach represents an intervention strategy that could be widely-disseminated and may provide stronger accountability/support than a one-on-one approach in some patients. Future work is aimed at refining strategies to increase patient enrollment/retention. Clinical trial information: NCT04855552. [Table: see text]
Phase II multicentric Italian trial on repositioning of the antipsychotic drug chlorpromazine and its combination with temozolomide in patients with MGMT unmethylated glioblastoma: The RACTAC trial.
Authors: Lombardi Giuseppe , Paggi Marco Giorgio , Matteoni Silvia , Villani Veronica , Benincasa Dario , Abbruzzese Claudia , Cerretti Giulia , Padovan Marta , Caccese Mario , Silvani Antonio , Pace Andrea
Published: June 2022

TPS2073

Background: The poor prognosis of patients affected by glioblastoma (GBM) prompts the search for new and more effective therapies, particularly for GBMs with unmethylated MGMT. In this regard, drug repurposing, can represent a safe and inexpensive way to bring novel pharmacological approaches from bench to bedside. Chlorpromazine, a medication in use since six decades for the therapy of psychiatric disorders, shows in vitro features that make it eligible for repositioning in GBM therapy. In our experimentation on six GBM cell lines, chlorpromazine inhibited cell viability in an apoptosis-independent way, induced polyploidy, reduced cloning efficiency as well as neurosphere formation and downregulated the expression of stemness genes. Notably, we found that chlorpromazine synergized with temozolomide, in reducing cell viability and strongly cooperated in reducing cloning efficiency and inducing cell death in vitro for all the GBM cell lines assayed. Methods: With these assumptions, we started a multicentric single arm Phase II clinical trial on newly diagnosed GBM patients with unmethylated MGMT by adding chlorpromazine to temozolomide in the adjuvant phase of the standard first-line therapeutic protocol. The experimental procedure involves the combination of CPZ with standard treatment with TMZ in the adjuvant phase of the Stupp protocol after radiochemotherapy combination. CPZ is administered orally at a dose of 50 mg/day – GG 1-28 – of every cycle of the adjuvant treatment with TMZ. At present, 38 patients out of 41 patients planned have been enrolled. Clinical trial information: NCT04224441.
A study of neo-adjuvant and adjuvant ofra-vec (VB-111) for treatment of surgically accessible recurrent GBM.
Authors: Wen Patrick Y. , Brenner Andrew J. , Butowski Nicholas A. , Rachmilewitz Minei Tamar , Harats Dror , Cloughesy Timothy Francis
Published: June 2022

TPS2075

Background: Ofranergene obadenovec (ofra-vec, VB-111) is an anti-cancer gene based immune activator and targeted vascular disruptor. The dual mechanism of action triggers a broad antiangiogenic effect and induces of a tumor directed immune response. A previous study demonstrated a survival benefit for patients with recurrent glioblastoma (rGBM) treated with ofra-vec monotherapy, that was continued after progression in combination with bevacizumab. Glioblastoma is an immunologically “cold” microenvironment which fosters immunosuppression and antagonizes anti-tumor immune responses. The role of T-cell infiltration in combating cancer has been increasingly recognized and associated with improved participant outcomes. Based on these observations, this study will assess the hypothesis that neoadjuvant use of ofra-vec will lead to a statistically significant increase in tumor infiltrating T lymphocyte (TIL) density within the tumor and enhanced systemic tumor-specific T cell responses. Methods: Study NCT04406272 is a multicenter, randomized, blinded, placebo-controlled, phase 2 surgical trial to evaluate early immunologic pharmacodynamic parameters for the viral cancer therapy ofra-vec in rGBM. 45 participants with rGBM indicated for resection will randomized to one of three treatment arms: Neoadjuvant Arm: intravenous ofra-vec prior to resection, and ofra-vec every 6 weeks after resection. Adjuvant Arm: placebo prior to resection, and ofra-vec every 6 weeks afterwards. The control arm will receive placebo prior to resection followed by standard of care. Upon evidence of contrast-enhancing progression, bevacizumab may be initiated as needed for supportive care; however, ofra-vec will continue until progression is supported at two consecutive time points. Tumor samples will be obtained and archived at the time of surgery, and blood samples will be obtained as pharmacodynamic markers throughout the study to allow DNA sequencing of T cells. The primary endpoint is to evaluate the influence of neoadjuvant ofra-vec on TIL density. Other endpoints include safety and tolerability, peripheral T cell response, 6mPFS and OS. Study is open for enrolment. Clinical trial information: NCT04406272.