bluuebunny/crossref_metadata_2025 huggingface dataset:
Knitting to improve cognition and reduce stress in cancer survivors: A pilot study.
Authors: Hartzell Jennifer W , Yaguda Susan , Boselli Danielle
Published: June 2021

e24049

Background: Cancer-related cognitive impairment (CRCI), or “chemo brain,” is defined by mild cognitive changes before, during or after cancer treatment. Objective deficits on neuropsychological tests are mild, while distress about cognitive issues is often high and interventions are lacking. Skill learning, which relies upon implicit memory, promotes functional and structural neuroplasticity. This has not been explored in CRCI. We designed a standardized protocol for learning to knit over 8 weeks and recruited consecutive cancer patients with subjective cognitive concerns. Cognition and perceived stress were assessed before and after learning to knit. Methods: Sixteen cancer survivors (N=16) without any known central nervous system disease or prior knitting experience completed the study. All were female and >80% were Caucasian. Mean age was 54 (SD=7) years. Mean education was 16 (SD=2) years. Neuropsychological tests were selected based on sensitivity to frontal lobe functions and memory and resistance to practice effects. Cognition and perceived stress were measured before and after the intervention, summarized, and compared using paired t-tests. P<0.1 was considered statistically significant. Clinically significant cognitive change was defined by ≥1 standard deviation change between pre- and post-intervention standardized scores. Results: Baseline cognitive function was average across domains. Baseline perceived stress was moderately high. At post-testing, there were statistically significant improvements in perceived stress, cognitive flexibility, and psychomotor speed. After controlling for demographic factors, clinically significant improvements in attention and memory were seen in 38% and 25% of subjects, respectively. 69% had clinical improvement in at least one cognitive domain. Conclusions: Learning to knit produced statistically and clinically significant improvements in cognition and perceived stress in cancer survivors in 8 weeks. Most had clinical improvement in at least one cognitive domain. This skill-based pilot study suggests functional neuroplastic change is possible in selected female, college-educated cancer survivors in a short timeframe and without technology use. Future research on the impact of skill learning on cognition and stress in larger, more diverse samples of cancer survivors may yield much needed interventions for CRCI.[Table: see text]
A cross-sectional study on the effectiveness of antiemetic regimens for chemotherapy-induced nausea and vomiting: A single center retrospect study of 1,000 patients.
Authors: Cong Luo , Shang Mingge , Chen Lei , Qi Xu , Jingjing Li , Wei Qing , Ying Jieer
Published: June 2021

e24055

Background: Chemotherapy-induced nausea and vomiting (CINV) is a common symptom in patients who undergoing chemotherapy, it is very important to control CINV to maintain dose intensity and patients' quality of life. To analyse the current situation of CINV for the tumor patients who undergoing chemotherapy, we used a cross-sectional survey to assess CINV status in those patients, and whether the drugs used by doctors in each department met the guidelines, and compared the efficacy of different antiemetic regimens on acute and delayed CINV overall post-chemotherapy periods. Methods: 1,000 patients were randomly selected from 5,468 patients with chemotherapy discharged from different departments of Zhejiang cancer hospital in China between April 1 and April 30, 2019, and there were 87 responses totally. Medical records were collected on patient’s department (internal medicine, surgery, radiotherapy, interventional) , chemotherapy regimens, anti-vomiting program, etc. Patients' feedbacks were recorded by CTCAE4.03 standard using MASCC antiemetic tool (Mat). Participants reported the frequency, severity, and impact on daily life of CINV from the day of chemotherapy administration up to 5 days thereafter and nausea and vomiting, as well as pharmacologic and chemotherapy used. Results: A total of 66 antineoplastic drugs were investigated, of which 52 were given intravenously and 14 orally.There were 9, 7, 50 drugs with high, moderate and low emetic risk respectively.The most prescribed prophylactic regimens for the management of CINV were aprepitant, 5-HT3R, H1-RA and dexamethasone and metoclopramide. The overall incidence of CINV were 44.34%, 24.57% and 39.66% patients reported nausea or vomiting in the acute and delayed phases. 19.89% patients had both acute and delayed CINV. The consistency rate of antiemetic with guideline was 63.19% in internal medicine department, 61.41% in surgery department and 52.91% in radiotherapy department, which showed a significant gap between the actual use of drugs and the recommended guidelines(P = 0.001). In 875 patients, 518 patients received guideline recommended antiemetic regimen, the CINV rates of complete response (CR), defined as no vomiting with no rescue medication, were 61.58%. While the CR rates in other 357 patients were 47.06%(P < 0.001). Nausea was more frequent across the overall observation period(43.77% VS 18.86%). However, vomiting was more sever and had a greater impact on life than nausea. Conclusions: Overall, adherence to the guideline recommendations in different departments were poor with varying degrees. Future studies should set hard outcomes, such as the absence of any symptoms, as a primary end point.The standardized management of CINV in patients needs to be further strengthened and doctors need to use drugs more regularly to reduce the occurrence of CINV in patients.
State variation in marijuana use among U.S. adults with cancer.
Authors: Lee Min Jee , Adjei Boakye Eric
Published: June 2021

e24064

Background: The number of cancer survivors in the United States (U.S.) is projected to exceed 20 million by 2024. More and more U.S. states are legalizing marijuana use for both recreational and medicinal purposes. This study estimated the prevalence of marijuana use by state among adult cancer survivors. Methods: U.S nationally representative, cross-sectional data from the 2018-2019 Behavioral Risk Factor Surveillance System Survey (BRFSS) Marijuana Use module were used. A total of 13,174 cancer survivors in 17 states was included. Analyses were weighted to account for BRFSS’s complex survey design with results generalizable to 5.7 million cancer survivors. The outcome variable was marijuana use in the past 30 days. Weighted prevalence estimates were computed. Weighted, multivariable logistic regression model estimated the association between state and marijuana use, adjusting for sociodemographic, health, and healthcare factors. Analyses were performed in January 2021. Results: The prevalence of past-month marijuana use among adult cancer survivors in these states was 9.2%. States varied widely in terms of the prevalence of marijuana use. Marijuana use was higher among those who resided in Guam (15.9%), followed by New Hampshire (13.1%), and lowest for those in Puerto Rico (3.3%) ( p< 0.0001). In the adjusted models, compared with the adult cancer survivors residing in California, those living in Maryland, Minnesota, North Dakota, Ohio, South Carolina, Tennessee, Utah, West Virginia, and Wyoming were significantly less likely to use marijuana. Conclusions: Nearly 9% of adult cancer survivors used marijuana, and those who resided in Guam, New Hampshire, Florida, and California are at higher risk for marijuana use. Given the increasing number of cancer survivors and the proliferation of marijuana legalization, identifying high-risk cancer survivors for marijuana use and informing physicians and patients about safe uses and doses and the potential adverse effects of marijuana use is critical.
A national survey on cancer pain management among medical oncologists in the Philippines.
Authors: Mendoza Marvin Jonne Limbo , Chua Alfredo Viray , Tan Patricia Grace Chua , Dofitas Carla Bonifacio , Villano Emmanuell , Santos Maria Dolma Gudez , Strebel Heinrik Martin Jude Sampedro
Published: June 2021

e24071

Background: Pain is one of the most burdensome symptoms of cancer. Although cancer pain management is an integral component in the practice of oncology, many patients still complain of insufficient pain control. Therefore, there is a need to pursue and strengthen strategies on how to adequately and effectively manage cancer pain. This study aimed to determine the knowledge and attitudes of Filipino medical oncologists regarding cancer pain management. It also examined the practices and perceived barriers in managing cancer pain. Methods: This was a cross-sectional study which utilized a validated questionnaire designed to assess a physician’s knowledge on pain management and opioid therapy, perceptions of the adequacy of cancer pain management, and significance of various potential barriers in optimal cancer pain management. Results: Out of the 280 PSMO members practicing in the Philippines, 85 responded to the survey. Using numeric rating scales of 0 to 10, medical oncologists appeared to agree on their knowledge about opioid therapy as well as in their perceptions of pain management. Respondents have rated themselves highly (Med: 8; IQR 6-8) in their ability to manage cancer pain. There were similar responses to ascribing all potential barriers as significant in rendering optimal cancer pain management, with cost as the most considerable factor (Med: 8, IQR: 7-10). However, given two challenging clinical scenarios, 66% and 90%, respectively endorsed treatment decisions that were unacceptable to pain experts. Conclusions: In this study, Filipino medical oncologists have shown agreement on their knowledge but perceived significant barriers in cancer pain management, with cost as the most considerable factor. Educational strategies, positive attitudinal change, and multidisciplinary collaboration with pain or palliative care specialists should be strengthened to improve patient care.
A randomized double-blind pilot study comparing cetirizine with diphenhydramine in the prevention of paclitaxel-associated infusion-related reactions.
Authors: Bouchard Philippe , Beaucage-Charron Johannie , Gaudet Laurence , Lamothe Sarah , Pelletier Cloé , Pépin Anne-Sophie , Roy Valérie , Charpentier Frédéric , Lordkipanidzé Marie , Projean Denis , Picard Matthieu
Published: June 2021

e24080

Background: Cetirizine is a less sedative alternative to diphenhydramine for the prevention of infusion-related reactions (IRR) to paclitaxel. However, there is no prospective data to support its use in this context. In this study, we conducted a feasibility study for a future definitive non-inferiority trial comparing cetirizine with diphenhydramine as premedication to prevent paclitaxel-related IRR. Methods: This was a single center randomized double-blind parallel-group prospective pilot study. Participants were paclitaxel-naive cancer patients scheduled to start paclitaxel chemotherapy, alone or in combination. They were assigned to receive either intravenous diphenhydramine 50 mg + oral placebo (diphenhydramine group) or intravenous placebo + oral cetirizine 10 mg (cetirizine group) for their first two paclitaxel treatments. To assess the feasibility of a larger study, the percentage of eligible patients completing a first paclitaxel treatment and the recruitment rate were calculated. IRR events were documented. Change in drowsiness compared with baseline was assessed using the Stanford Sleepiness Scale (SSS). Results: Among 37 eligible patients, 27 were recruited and randomized (control 13; intervention 14) and 25 completed the study. The recruitment rate was 4.8 participants/month, meeting the primary feasibility target of 4 participants per month. One participant had an IRR (cetirizine group, CTCAE grade 2) and no unexpected serious adverse events occurred. Drowsiness was the main adverse effect associated with the premedication. The increase in drowsiness compared to baseline (ΔSSS) was greater in the diphenhydramine group compared to the cetirizine group (median ΔSSS 2 (IQR 3.25) vs median ΔSSS 0 (IQR 1), p < 0.01) when measured one hour after the administration of the premedication. Patient self-assessed moderate or intense discomfort caused by drowsiness was exclusively reported in the diphenhydramine group, by 4 out of 13 participants. Conclusions: The trial methods were feasible in terms of recruitment rate, retention and patient safety. IRR were infrequent and a larger trial is warranted to confirm non-inferiority for IRR prevention. Cetirizine was significantly less sedating than diphenhydramine when administered as premedication to prevent paclitaxel-associated IRR. Clinical trial information: NCT04237090. [Table: see text]
Prediction of the breakthrough cancer pain using deep learning model.
Authors: Bang Yeong Hak , Choi Yoon Ho , Park Mincheol , Lee Geon Hee , Shin Soo-yong , Kim Seok Jin
Published: June 2021

e24085

Background: Breakthrough cancer pain (BTcP), a transitory flare of pain that occurs on a background of relatively well-controlled baseline pain, is a challenging clinical problem in managing cancer pain. We hypothesized that the BTcP could be predictable according to the patients’ previous observed patterns. In this study, we report on the development of a deep learning model that predicts hourly individual-level breakthrough pain for patients with cancer. Methods: We defined the BTcP as the pain with numerical rating scale (NRS) score 4 or above and developed models predicting the onset time of BTcP with the temporal resolution of 1 hour. The datasets which have more than 20 records of NRS score during hospitalization were included in our study. All the pain records were obtained from patients hospitalized on the wards of hematology-oncology in Samsung Medical Center between July 2016 to February 2020. The model used the time windows of 3 days to predict NRS scores over the next 24 hours. To capture irregular pain patterns, we created the sequence of average pain patterns over 24 hours from the previous 3 days and used it for normalization. We trained a Bi-directional long-short term memory (LSTM) based deep learning model. The model was validated using the holdout method with 20% of the datasets. Its performance was assessed with the area under the receiver operating characteristic curve (AUROC) and the area under the precision-recall curve (AURPC). Results: We included pain log data containing 2,905 admissions from 2,176 patients with solid cancer and 1,755 admissions from 1,082 patients with hematologic cancer in the analysis. The median age was 57 (interquartile range (IQR), 47-64), the most frequent type of cancer was lung cancer (18.0%), and most patients had stage 4 (60.7%). Among the 103,948 hours from patients in whole datasets, 1,091 (4.7%) hours were labeled as the period of BTcP. The patients have the records of NRS score with a median of 3 (IQR, 2.0-4.5) and BTcP with a median of 1.1 (IQR, 0.5-2.0) per day. We allocated approximately 20% of patients (653 patients with 932 admissions) to the holdout test dataset. Our model showed the AUROC 0.719 and AUPRC 0.680 for predicting the BTcP in the test dataset. Conclusions: Our study showed that cancer pain could be predictive by using a deep learning model. Though our exploratory study has a limitation of generalizability, future warranted subgroup analysis and verification research could make our model more applicable in a real-world setting.
ICES (International Carboplatin Emesis Survey) for the evaluation of the emetogenicity of continuous cycles of carboplatin-based chemotherapy with focus on nausea: A MASCC emesis study group, prospective, observational, real-world multi-centric study.
Authors: Rapoport Bernardo Leon , Chan Alexandre , Chasen Martin Robert , Smit Teresa , Heyman Liezl , Tan Chia Jie , Bhargava Ravi , Bosnjak Snezana , Zilic Ana , Jabbar Adnan Abdul , Zhang Yaxiong , De Necker Margreet , Mhazo Tina V
Published: June 2021

e24086

Background: Chemotherapy induced nausea and vomiting (CINV) following carboplatin containing chemotherapy regimen remains a considerable problem for cancer patients (pts) despite standard antiemetic prophylaxis. This study was undertaken to prospectively evaluate the incidence of CINV in pts undergoing carboplatin-based chemotherapy receiving guidelines consistent CINV prophylaxis (GCCP). All sites did not prescribe NK1-RA as it is not included in all institutional guidelines. Methods: The study enrolled 207 pts undergoing carboplatin-based chemotherapy, the final analysis evaluated cycle 1 - 6 with a total of 183 evaluable pts from 6 countries. Pt diaries were used to collect data from day 1-10 beginning with cycle 1. Nausea was reported by the pts using a visual analog scale (VAS) with the end-point being no nausea. Vomiting episodes were recorded in the pts’ diaries. Demographic, occurrence and severity of emesis, numbers of emetic episodes and time to the onset of emesis, were summarized using descriptive statistics. Results: There were 129 females and 54 males. The overall incidence of acute and delayed nausea for was 17% and 25% respectively. The incidence of nausea of entire population was significantly higher than vomiting (58% vs. 14%; Chi2 22.271 p<0.000). The use of NK1-RA was associated with a significant decrease in time to first vomiting for cycle 1 (p<0.041) and subsequent cycle 2-6 (p<0.0075). Additional results are reported in the Table. In a logistic regression model factors associated with acute nausea in cycle 1 included history of motion sickness (p< 0.0090), comorbidities (p< 0.0084), history of morning sickness (p< 0.0090), previous chemotherapy (p< 0.0096), anemia (p< 0.0209). A separate logistic regression analysis for delayed nausea in cycle 1 showed that prior radiotherapy (p<0.0093) and a history of morning sickness (p<0.0195) were also significant. During subsequent cycles (1 – 6), the incidence of nausea remained higher than vomiting and was documented in the acute and delayed phases ranging from 6% to 25%. The use of NK1-RA was associated with a lower incidence of vomiting during cycle 1-6 with 91% patient receiving NK1-RA experiencing no vomiting vs 78% of patients not receiving NK1-RA with no vomiting (log rank = 0.0287). Conclusions: Despite GCCP and the usage of NK1-RA, carboplatin induced nausea remains a major unmet medical need in cancer pts. Further research should focus on management of nausea, risk factors and the impact of nausea on quality of life and in pts undergoing carboplatin-based treatment.[Table: see text]
Implementation of virtual mentoring to optimize collection of patient-reported data in the COVID-19 era: A prospective cohort study with adaptive design.
Authors: Kazazian Karineh , Bogach Jessica , Johnston Wendy , Swallow Carol Jane
Published: June 2021

e24091

Background: Prior to the COVID-19 pandemic, all patients attending ambulatory clinic at cancer centers in Ontario, Canada completed the Edmonton Symptom Assessment Scale (ESAS), as per governmental cancer agency mandate. At our center, completion was via touch pad, with assistance by clinic volunteers. As of mid-March 2020, clinic appointments were conducted virtually whenever possible, and touch pads removed from clinic. Our purpose here was to explore how these changes impacted the collection of patient-reported outcomes, in particular the recognition of severe symptoms. Methods: We performed a prospective cross-sectional cohort study to test the feasibility of remote completion of the ESAS by patients scheduled for appointments at a weekly surgical oncology clinic at a major cancer center. Patients were identified serially based on date of clinic appointment. Patients in the initial study cohort were asked to complete and return the ESAS virtually (V). Given low completion rates, the ensuing study cohort was asked to complete a hard-copy (HC) ESAS. For the final cohort, we used an adaptive approach, providing remote, personal mentoring by a member of the health care team to support virtual ESAS completion (virtual-mentored, VM). Results: Between May-July 2020, a total of 174 patients were included in the study: 53% were female, and median age was 62 (19-90) yrs. Age, gender and tumor site did not differ between the three cohorts. For the V cohort, 20/43 patients successfully completed and returned the ESAS electronically (completion rate 44%). For the HC cohort, 49/50 completed the form (98%). For the VM cohort (n=78), the completion rate was 74%. Questionnaire completion was not predicted by age, gender or tumor site, although patients who completed the ESAS were more likely to be under active investigation/treatment vs. surveillance (p=.04). Of the 127 ESAS forms completed in all patient cohorts, 117 reported at least 1 symptom score ≥1. There were no significant differences in individual symptom scores (e.g. tiredness, wellbeing-see Table) reported between cohorts. Of all completed forms, 42% had a depression score ≥2 and 27% an anxiety score ≥4, indicating significant psychosocial distress. Conclusions: We have identified significant barriers to the virtual completion of ESAS forms, with lack of predictive variables. The severe degree of psychological distress reported by ̃50% of respondents demonstrates the need for ongoing regular collection and review of these data.[Table: see text]
Granisetron extended-release subcutaneous injection versus palonosetron infusion for preventing chemotherapy-induced nausea and vomiting: A cost analysis.
Authors: Kumar Vikas , Barnes Martin , Calcanes George , Mosier Michael , Virgilio Danille , Vacirca Jeffrey L.
Published: June 2021

e24093

Background: Unscheduled hydrations (UHs) can significantly increase the cost of care in patients receiving moderately or highly emetogenic chemotherapy (MEC or HEC). Granisetron extended-release subcutaneous injection (GERSC) is a unique formulation of granisetron for prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV). Limited data are available regarding the impact of GERSC on cost of UHs compared to other antiemetics. Objective: Assess costs of an UHs associated with breakthrough CINV following GERSC or palonosetron (PALO) for preventing CINV in patients receiving MEC or HEC. Methods: Retrospective analysis of medical records from a single multicenter community-based practice involving patients receiving MEC or HEC with a 3-drug antiemetic regimen (neurokinin-1 receptor antagonist, dexamethasone, and either GERSC or PALO). Cost of care analysis for GERSC and PALO was based on maximum per-unit Medicare reimbursement for UHs, rescue antiemetic drugs and administration, laboratory, and office evaluations. Results: 182 patient records (n = 91 GERSC; n = 91 PALO) were evaluated. A lower number of median UHs per-patient were observed following GERSC versus PALO (HEC, 3 vs 5) and (MEC, 2 vs 3). Mean cost of care related to UHs was significantly lower per-patient following GERSC ($296, n=91) versus palonosetron ($837, n=91) ( P < 0.0001), including when the subset analysis was restricted to those patients requiring hydration (Table).When analyzing individual components of care, hydration (CPT codes 96360 and 96361) costs per-patient receiving HEC or MEC were lower following GERSC ($62, n=91) versus PALO ($253, n=91) ( P < 0.0001). Lower per-patient costs were observed following GERSC in all components of care except rescue antiemetic drug costs in MEC patients. Conclusions: GERSC reduced total per-patient costs of care associated with UHs visit relative to PALO in patients receiving HEC or MEC.[Table: see text]
Brain correlates of chemotherapy-induced peripheral neuropathy (CIPN) during somatosensory and interoceptive attention: A functional MRI (fMRI) study.
Authors: Kleckner Ian , Kleckner Amber , Belcher Elizabeth , Xu Huiwen , Lin Po-Ju , Dunne Richard Francis , Janelsins Michelle Christine , Kesler Shelli R. , Mustian Karen Michelle
Published: June 2021

e24095

Background: Over half of patients receiving neurotoxic taxane, platinum, or bortezomib chemotherapy experience CIPN—a dose-limiting toxicity involving numbness and pain in the extremities. There are limited biomarkers and treatments for CIPN partly due to lack of knowledge of its pathophysiology. Here, we studied whether CIPN involves changes in the brain’s sensory processing circuitry to inform novel brain-based biomarkers and brain-based treatments for CIPN. Methods: Eleven patients scheduled to receive taxane, platinum, or bortezomib rated CIPN severity (CIPN-20) and completed an fMRI scan before starting neurotoxic chemotherapy and/or 12 weeks later. The 7-min fMRI task involved alternating 20-sec trials of distinct attentional focus: (1) their left fingertips (somatosensory attention), (2) their heart (interoceptive attention), and (3) a flashing word “target” (visual attention; the reference condition). We found an activation cluster in primary somatosensory cortex (S1) comparing somatosensory vs. visual attention and another cluster in primary interoceptive cortex (mid/posterior insula) comparing interoceptive vs. visual attention. We tested for associations between CIPN severity and task-based activations in S1 and the insula. Because this is a pilot study, we present effect sizes (ESs) using Cohen’s d and Pearson’s r, not p-values. Results: The 11 patients were 63±12 years old, 54% women, and 54% had breast cancer with high-quality fMRI data (16 scans; 8 pre-chemotherapy). As expected, somatosensory attention increased activation in S1 compared to visual attention (ES = 1.46), and interoceptive attention increased activation in the insula compared to visual attention (ES = 0.94). Patients with worse CIPN had smaller increases in S1 activation during somatosensory vs. visual attention (ES = 0.38), suggesting reduced S1 activation during somatosensory attention (i.e., failure to activate S1) and/or increased S1 activation during visual attention (i.e., S1 chronically activated). Similarly, patients with worse CIPN had smaller increases in insula activation during interoceptive vs. visual attention (ES = 0.57). Individual differences in S1 or insula activity were not significantly explained by age, anxiety, or problems remembering (all ESs < 0.12). Conclusions: CIPN severity was associated with changes in brain activity during a simple attentional task during fMRI scanning, implicating the brain’s somatosensory and interoceptive processing in CIPN. Future work should test for replication and develop biomarkers and treatments for CIPN that target somatosensory and interoceptive processing, perhaps using this attention task. NCT03021174. Funding: NIH R25CA102618, UG1CA189961, K07CA221931. Clinical trial information: NCT03021174.
Prognostic disclosure: A scoping review on communication guidelines and their application in oncology.
Authors: Bloom Julie R , Marshall Deborah Catherine , Rodriguez-Russo Carlos , Martin Emily J , Jones Joshua Adam , Dharmarajan Kavita Vyas
Published: June 2021

e24107

Background: Prognostic disclosure is essential to informed decision making in oncology, yet many oncologists are unsure how to successfully facilitate this discussion. This scoping review determines what prognostic communication guidelines exist, compares and contrasts these guidelines and explores the supporting evidence. Methods: A protocol was created using the Preferred Reporting Items for Systematic Reviews and Meta-analysis Protocols extension for Scoping Reviews. Comprehensive literature searches of MEDLINE, EMBASE, PsychINFO, and Cochrane CENTRAL were performed to identify relevant publications between 1971 and 2020. Results: In total, 1532 articles were identified, of which 78 met inclusion criteria and contained 5 communication guidelines. Three guidelines have been validated in randomized control trials (Serious Illness Conversation Guide (SICG), The Four Habits Model and ADAPT) and demonstrated improved patient reported outcomes and objective communication measures. Among guidelines’ core principles, 3 concepts are common to all: patient’s understanding and preference, prognosis, and responding to emotion. Conclusions: Communicating prognosis is a core competency skill in cancer care, yet remains underprioritized in training and practice. This review highlights available models and acknowledges areas in need of further understanding including how to maintain learned communication skills for lifelong practice.[Table: see text]
The influence of clinical stage, race, and gender on factors which impact quality of life in multiple myeloma.
Authors: Luhowy Meghan , Binion Katrina , Warfield Tiffany , Bosley Rebecca , Krauss Elizabeth , Badros Ashraf
Published: June 2021

e24126

Background: Multiple myeloma (MM) is unique among hematologic malignancies as an incurable disease. Patients are affected long-term by the disease symptoms as well as psychological, financial burden, and social impact, which may affect overall quality of life (QOL). The current literature related to QOL in MM is largely limited to a single clinical stage, impact concurrent with a specific treatment regimen, or focused on a single QOL factor. Changes in impact on QOL based on longitudinal follow up during the disease course have not been readily assessed. Here, we evaluated patient-reported QOL measures utilized by one time validated questionnaires. Methods: The study enrolled 100 participants in a sequential manner from the Myeloma Clinic at UMGCC with a diagnosis of plasma cell disorders at various stages: MGUS, smoldering myeloma, or multiple myeloma: newly diagnosed, maintenance, relapsed. Participants provided verbal responses to a series of questions listed in Table. Questions aligned with three main domains: physical symptoms and function, mental health, and social systems. The following is an interim analysis of the first 50 patients. Results: This sample of myeloma patients (N=50; males n=26), felt their QOL was impacted by myeloma symptoms (70%). More African American participants reported impact from financial burden (6, 50%) in comparison to Caucasian and other races (10, 26%). Interestingly, males reported less impact on sexual intimacy (3, 15%) than females (6, 43%). Females also reported more impact from financial burden (10, 42%) compared to males (6, 23%). Conclusions: Changes to impact on QOL as a function of clinical MM stage, race, and/or gender will be fully evaluated. Planned analyses include correlation statistics by age and social demographics to determine patterns in patient-reported outcomes. Finally, second interviews with current participants will be conducted to determine changes to impact across the same QOL variables over time.[Table: see text]
Revamping the delivery of cancer support, education, and wellness programming during the COVID-19 pandemic.
Authors: Capparella Lisa , Lopez Ana Maria , Naputo Kristine , O'Hayer C. Virginia Virginia , Garber Gregory D. , Leader Amy , Pomerantz Miriam
Published: June 2021

e24127

Background: Supportive care is considered essential to standard care for patients with a history of cancer. The interdisciplinary team at Sidney Kimmel Cancer Center (SKCC) of Thomas Jefferson University, an NCI-designated cancer center in Philadelphia, offers a robust variety of supportive care services including support groups, educational and wellness programs. SKCC includes four academic hubs across the Greater Philadelphia region. With the onset of the COVID-19 pandemic and the subsequent statewide shutdown of services, SKCC quickly pivoted to virtual offerings, to address patients’ supportive care needs. Recent research has shown patients self-reporting higher incidence of anxiety and loneliness due to the pandemic. Direct patient feedback identified programs of greatest need, the preferred times and format. Methods: At the beginning of the pandemic SKCC offered a program “Coping with Cancer and Covid-19: as You Navigate Cancer Treatment.” This program helped patients understand their risk of COVID-19 and provided emotional support as patients and caregivers began facing loneliness. Additional virtual offerings included Mindfulness Sessions, Yoga, Stretching for Stress Relief, Healing through Humor. SKCC began evaluating the impact of the programming beginning in June 2020. Attendees completed surveys evaluating the presentation, their level of psychological distress, perceived quality of life, and feelings of hope, loneliness, and connection. Participants were asked if they would attend another program and were asked to rate the program on a Likert scale. Results: In 2019 SKCC offered 273 programs and attracted 984 participants. Only 90 of the 984 participants attended virtually prior to the pandemic. Since the start of the pandemic, SKCC has hosted 334 programs, all virtually, with 3,346 participants. Surveys were sent electronically and completed immediately after the completion of all support programs offered at SKCC. 40% of program participants’ completed an evaluation form and 94% rated the program exceptional or very good. Overall, 88% of participants in virtual wellness, support groups and educational programs indicated they would attend another program offered by SKCC. Conclusions: Virtual supportive care offerings have engaged more patients and caregivers than ever across SKCC hubs and have proven an effective means to continue to support patients during the pandemic. It is important to continue to evaluate and create meaningful programs to match the ongoing needs of patients and caregivers.[Table: see text]
Phase II study of nivolumab and ipilimumab in children and young adults with INI1-negative cancers.
Authors: Forrest Suzanne J. , Yi Joanna , Kline Cassie , Cash Thomas , Reddy Alyssa Terry , Cote Gregory Michael , Merriam Priscilla , Czaplinski Jeffrey , Bhushan Ketki , DuBois Steven G. , Janeway Katherine A. , Kao Pei-Chi , London Wendy B. , Chi Susan N. , Collins Natalie Bucheimer
Published: June 2021

TPS10055

Background: Several aggressive pediatric and young adult cancers are characterized by SMARCB1 inactivation resulting in loss of INI1 expression, including rhabdoid tumors, epithelioid sarcoma and undifferentiated chordoma. These malignancies are associated with a poor prognosis and few effective treatment options for relapsed or refractory disease. Prior studies and emerging data suggest INI1-negative cancers may be uniquely susceptible to treatment with immune checkpoint inhibitors: Many INI1-negative pediatric tumors express PD-L1 and are infiltrated by immune cells, and there are reports of patients with advanced INI1-negative cancers with clinical responses to immune checkpoint blockade (Forrest et al. Clinical Cancer Research, 2020). We hypothesize that INI1 loss predicts tumor response to immune checkpoint inhibition (ICI). Methods: This is an ongoing multicenter, phase II, open-label clinical trial to evaluate the activity of nivolumab and ipilimumab in patients aged 6 months to 30 years with relapsed or refractory INI1-negative cancers (NCT04416568). The study enrolls patients in 2 strata: extracranial solid tumors in Stratum 1 and intracranial solid tumors in Stratum 2. Patients treated with prior ICI are excluded. Patients are treated with intravenous (IV) nivolumab 3mg/kg plus ipilimumab 1mg/kg IV every 3 weeks for 4 cycles followed by nivolumab 3mg/kg (max dose 240mg) IV every 2 weeks for up to 1-year. The primary objective is to evaluate the objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) for Stratum 1 and by Response Assessment in Neuro-Oncology (RANO) criteria for Stratum 2. The trial has a 2-stage design targeting a 25% or greater response rate, with each stratum assessed independently. The analysis for Stage 1 in a given Stratum will be performed after 10 patients are enrolled. If a sufficient number of responders are observed, an additional 10 patients will be enrolled at Stage 2. Secondary endpoints include progression-free survival, overall survival, and disease control rate at 12 months. Correlative aims include assessing tissue and blood biomarkers associated with treatment response. Enrollment began 14 Aug 2020 and is ongoing. Clinical trial information: NCT04416568.
Comprehensive ambulatory monitoring during immunotherapy in patients with advanced melanoma: A prospective trial (CAMP-IT).
Authors: Kos Milan , Buffart Laurien , de Groot Jan Willem , Westgeest Hans , Dercksen Wouter , Van Laarhoven Hanneke W.M. , van Oijen Martijn G.H.
Published: June 2021

TPS1589

Background: The emergence of immune checkpoint inhibitors has improved survival outcomes for patients with advanced melanoma. However, these treatment modalities are also associated with specific immune-related toxicities. These are often reversible after prompt recognition and initiation of appropriate management, but can result in severe morbidity and hamper health-related quality of life (HRQoL) if left undetected. Hence, accurate and regular monitoring of these patients is critical. Recent advances in mHealth technologies and the rapidly expanding armamentarium of wearable devices allow for real-time objective (vital signs and physical activity) data and patient-reported outcome measurement (PROMs) collection and, hence, serve this purpose. We hypothesize that collection of real-time objective data adds to the early detection of disease- and treatment-related adverse events. The primary objective of this study is to determine the feasibility of collecting real-time PROMs, vital signs, and physical activity data in advanced melanoma patients receiving immunotherapy using a comprehensive ambulatory monitoring platform (CAMP) that consists of a smartphone app, activity monitor, digital thermometer, and online dashboard for physicians. Methods: In this prospective multi-center trial, patients (n = 50) with advanced melanoma, scheduled to receive immunotherapy with immune checkpoint inhibitors, and with access to a smartphone are eligible for inclusion. Consenting patients will be asked to wear a FitBit Versa 2.0 during waking hours, collect daily temperature measurements using a Withings Smart Temporal thermometer, and answer weekly toxicity questionnaires (NCI PRO-CTCAE) using the smartphone app for the duration of the study (12 weeks). Primary outcome is feasibility in terms of (i) participation rates, (ii) wear-time, (iii) compliance rates with in-app questionnaires and temperature measurements, and (iv) satisfaction with the platform. Secondary exploratory outcomes include associations between CAMP-derived parameters and clinical outcomes: performance status (PS), HR-QoL scores (EORTC QLQ-C30 questionnaire), unplanned hospitalizations, physician-assessed adverse events, and 1-year survival outcomes. PS and HR-QoL will be rated at baseline, mid-study, and end-of-study. The occurrence of adverse events will be documented up to 12 months from baseline. Survival outcomes will be compared to a propensity score matched group from the Netherlands Cancer Registry. Accrual has started in February 2021. Clinical trial information: NL8827.
First-in-human dose escalation and food effect study of oral ONC206 in adults with recurrent primary CNS neoplasms.
Authors: Theeler Brett James , Jung Jinkyu , Burton Eric , Leeper Heather , Wu Jing , Zaghloul Kareem , Ray-Chaudhury Abhik , Quezado Martha , Raffeld Mark , Yuan Ying , Aldape Kenneth D. , Penas-Prado Marta , Prabhu Varun Vijay , Stogniew Martin , Allen Joshua E. , Armstrong Terri S. , Gilbert Mark R.
Published: June 2021

TPS2072

Background: The majority of recurrent CNS tumors lack effective systemic therapy options following surgical resection and adjuvant radiotherapy. ONC201, the founding member of the imipridone class of small molecules, has induced durable tumor regressions in patients with diffuse midline glioma, H3 K27M-mutant (DMG H3K27M). ONC206, the second imipridone to enter clinical development, is a DRD2 antagonist and ClpP agonist that exhibits differentiated receptor pharmacology and gene expression profiles in tumors relative to ONC201. The compound is orally bioavailable, penetrates the blood-brain barrier, and exhibits anti-cancer efficacy without toxicity in several preclinical cancer models with pronounced efficacy in myc-overexpressing CNS tumors. Methods: A first-in-human, open label, dose escalation, and food effect Phase I study of oral ONC206 (NCT04541082) is currently enrolling. Patients must be 18 years or older and diagnosed with a recurrent, primary CNS neoplasm. Eligible diseases include recurrent glioblastoma, WHO Grade 2 and 3 infiltrating glial neoplasms, DMG H3K27M, ependymoma, medulloblastoma, malignant meningiomas, and other rare primary CNS neoplasms. Dose escalation, initially with weekly dosing, will follow a standard 3+3 design. After the MTD is established, a food effect cohort will enroll with a balanced, single-dose, two-arm, two-period, crossover design. The primary endpoint is to determine DLT during the first 28-day cycle. Secondary endpoints will include objective response rate by RANO criteria, overall and progression-free survival, and disease control rate. Exploratory biomarker analyses based on preclinical correlations with efficacy will include DRD2, DRD2 dimer, ClpP, DRD5, c-myc, and n-myc expression. Clinical trial information: NCT04541082.
Phase I study investigating the safety of stereotactic body radiotherapy (SBRT) with anti-PD-1 and anti-IL-8 for the treatment of multiple metastases in advanced solid tumors.
Authors: Karapetyan Lilit , Olson Adam C. , Gooding William E. , Bao Riyue , Chmura Steven J. , Luke Jason J.
Published: June 2021

TPS2681

Background: Anti-PD-(L)1 immunotherapy improves outcomes for patients across various cancers; however, many patients do not benefit. Previous studies combining multi-site SBRT with anti-PD1 have confirmed feasibility and revealed induction of interferon signaling by SBRT. Elevated levels of serum IL8 (sIL8) associate with lack of response to anti-PD1 and we have observed that elevated IL8 is strongly associated with lack of response to immunotherapy and SBRT combinations. Overcoming IL8 induced epithelial-mesenchymal transitioning and trafficking of myeloid derived suppressor cells in tumor microenvironment therefore represents a promising strategy to overcome resistance. BMS-986253 is a fully human neutralizing antibody that binds to sIL8. The combination of BMS-986253 and nivolumab was safe in patients with advanced solid tumors. The present study aims to evaluate safety and preliminary efficacy of combining BMS-986253 with nivolumab and SBRT in patients with advanced solid tumors, Melanoma (MEL) and Renal Cell Carcinoma (RCC). Methods: This is a phase 1 open label single arm study (CT.gov: NCT04572451) which will include safety and efficacy cohorts. Patients will receive SBRT in 1-4 tumor lesions, in 3 or 5 fractions, at the total of 30 or 45 or 50 Gy based on the irradiated organ site. This will be followed by intravenous (IV) nivolumab (480mg q4 weeks (W)) and IV BMS-986253 (2400mg q2W) within seven days of completing SBRT. In the initial safety portion of the clinical trial, we will include 30 patients with advanced/metastatic solid tumors in order to evaluate safety. The primary endpoint of dose limiting toxicity will be assessed by continual Bayesian monitoring. The toxicities will be attributed to combination of SBRT/Immunotherapy as opposed to individual components. The secondary objective of the study is efficacy with an endpoint of objective response rate (ORR) as assessed by RECIST v1.1 in Mel and RCC. We will include 20 patients with MEL and RCC and compare against a historical benchmark of 20% ORR as sufficient signal of activity for further study. ORR will be assessed for association with serum IL-8 levels and radiation-induced changes in peripheral blood T cell populations. Clinical trial information: NCT04572451.
Phase 1b dose escalation study to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of GS-3583, a FLT3 agonist Fc fusion protein, in patients with advanced solid tumors.
Authors: Brody Joshua , Thompson John A. , Tolcher Anthony W. , Kuhne Michelle R. , Huang Xi (Rochelle) , Kwan Ellen , Petrarca Michael , Dauki Anees , Singh Indrajeet , Rajakumaraswamy Nishanthan , Kummar Shivaani
Published: June 2021

TPS3147

Background: Productive antitumor immune responses in nonclinical models depend on a type of dendritic cell (DC), conventional DC subtype 1 (cDC1), which in the context of cancer, primes tumor-reactive T cells through presentation of tumor-derived antigens. FMS-related tyrosine kinase 3 ligand (FLT3L) is a hematopoietic growth factor that binds to and activates FLT3 on terminally differentiated DCs. Activated FLT3 promotes proliferation, inhibits cell death, and is required for the differentiation, expansion, and maintenance of DCs in peripheral and lymphoid organs. GS-3583 is a fusion protein composed of the extracellular domain of recombinant human FLT3L fused to an engineered fragment crystallizable (Fc) region of human immunoglobulin G4. GS-3583 has PK properties that support sustained cDC in patients and potential combination with established immunotherapies. This phase 1b, open-label, multicenter, dose-finding study will evaluate safety, tolerability, PK, and preliminary efficacy of GS-3583 monotherapy in patients with advanced solid tumors (NCT04747470). Methods: Approximately 33 adults aged ≥18 years with a histologically or cytologically confirmed locally advanced or metastatic malignant solid tumor that is refractory to or intolerant of standard therapy or for which no standard therapy is available will be enrolled. The study employs a 3+3 dose escalation design in which GS-3583 is administered intravenously for up to 52 weeks or until progressive disease or unacceptable toxicity. Up to five dose escalation cohorts have been planned. The maximum tolerated dose is the highest dose with incidence of DLT in < 33% of 6 or more patients in the first 28 days of GS-3583 dosing; recommended phase 2 dose will be determined. Assessments include safety, PK, pharmacodynamics including cDCs, immunogenicity, and efficacy by RECIST 1.1 in CT/MRI imaging conducted every 8 weeks. Accrual at approximately 3-4 centers in the US is ongoing. Clinical trial information: NCT04747470.