bluuebunny/crossref_metadata_2025 huggingface dataset:
Is Karnofsky performance scale a proxy measure of frailty phenotype in older adults with cancer?
Authors: Parala-Metz Armida , Lasheen Wael , Haggstrom Daniel Ernest , Induru Raghava Reddy , Caprio Anthony James , Walsh Declan
Published: June 2023

e24035

Background: The use of performance status (PS) assessments in patients with cancer is a common practice to determine their suitability for treatment, clinical trial enrollment, and prognosis. The Karnofsky Performance Scale (KPS) and Eastern Cooperative Oncology Group Performance Status (ECOG PS) score are widely used clinical instruments for this purpose. However, these tools are subjective and unidimensional, with potential for bias, and were validated in younger patients. KPS has demonstrated greater specificity than ECOG in evaluating PS. Frailty, a dynamic medical syndrome characterized by diminished strength, endurance, and reduced physiological function, is recognized as a predictor of vulnerability to adverse outcomes, especially in older adults with cancer. The Fried Frailty Phenotype (FP) is a widely validated tool that uses both objective and subjective measures to identify frailty based on presence of 3 or more criteria: unintentional weight loss, self-report of exhaustion (fatigue), weakness (measured by grip strength), slow walking speed, and low physical activity. Our study compares physician-rated KPS with FP (fit, prefrail, frail) and looks at correlation of both tools in older adults with cancer. Methods: Data from older adults with solid tumor malignancies referred to the geriatric oncology clinic for geriatric assessment (GA) from January 2015–August 2019 were abstracted. Physician-rated KPS (0-100) were categorized into 3 groups: normal activity, high functioning (80–100); intermediate, capable of self-care but unable to do active work (70); and poor PS, requires considerable assistance (<60). These were compared to FP which classified patients based on the number of frailty criteria present: fit (0), prefrail (1-2), and frail (>3). Frequency data calculation and bivariate analysis were done. Results: 241 older adults with cancer completed a GA, median age of 80 years, 52% female. 57% were frail, 37% prefrail, and 6% fit. 90% of patients with KPS 80-100, had prefrail and frail phenotypes. Patients with KPS 70 had 24% prefrail and 76% frail phenotypes and those with KPS < 60 had 10% prefrail and 90% frail phenotypes. Conclusions: Majority of older patients with prefrail and frail phenotypes were assessed as high functioning (KPS 80-100). KPS is an inadequate substitute for FP and should not be used alone in assessing functional status of older adults with cancer.
The SMILE scale: A pilot study among patients with cancer.
Authors: Vater Laura , Ajrouch Ali , Monahan Patrick O. , Jennewein Laura , Han Yan , Karkash Ahmad , Hanna Nasser H.
Published: June 2023

e24036

Background: In the US, it is projected that more than 22 million people will be living with cancer by 2030. As survivorship increases, there is a need for simple, convenient tools to quantify patient quality of life and encourage healthy behaviors. To fill this gap, a new psychometric tool named the SMILE Scale was created. The SMILE Scale is a brief self-administered questionnaire assessing the frequency of behaviors intended to improve wellness in five domains: Sleep, physical activity (Move), stress management (Inhale and Exhale), social interactions (Love and connect), and nutrition (Eat to nourish). In this study, we aimed to determine the feasibility of collecting daily self-reported SMILE Scale data and weekly quality of life data, via electronic surveys in patients with cancer. We also aimed to measure the association between SMILE Scale responses and validated health-related quality of life (HRQOL) tools (PROMIS-29+2 and SymTrak-8) as a pilot test of the hypothesis that increased wellness behaviors may impact quality of life. Methods: We surveyed 100 patients with cancer at the IU Simon Comprehensive Cancer Center. Participants were asked to complete daily SMILE Scale assessments over a two-week period, as well as weekly PROMIS-29+2 and SymTrak-8 surveys. The primary endpoint was the SMILE Scale completion rate. Secondary endpoints in this single-arm pilot study included correlations between SMILE Scale results and the other HRQOL tools. Results: Daily completion rate of the SMILE Scale ranged from 57% to 65% of participants over a 14-day period. Among the 61% of participants who completed SMILE on day 1, 87% completed SMILE on 10 of 14 days. Further, 77% completed SMILE at least 1 of the 14 days. By end of study, participants who self-reported more wellness behaviors (i.e., higher daily SMILE scores) demonstrated significantly higher PROMIS physical health (p = .003), higher PROMIS mental health (p = .008), and lower (better) SymTrak total symptom burden (p = .006). Further, among those who completed at least 1 of 14 daily SMILE assessments, quality of life significantly improved over the two-week period for PROMIS mental health (p = .018) and SymTrak total symptom burden (p = .014). Conclusions: The SMILE Scale completion rate on any given day did not satisfy our pre-planned ≥70% threshold for feasibility; however, the rate for completing SMILE at least once during the 14 days (77%) met this threshold. There is growing recognition that interventions with modest uptake may benefit interested patients. The SMILE completion rate across 14 days among those who completed at least one day indicates benefit for providing a daily or on-demand option for those interested. Further, significant correlative results between SMILE scores and secondary QOL endpoints suggest a potential benefit for delivering SMILE in clinical practice and warrants testing the SMILE Scale’s causal impact in a future randomized trial.
Exploring the benefits of therapeutic horticulture in patients in gynecologic oncology: A pilot study.
Authors: Jhaveri Vasanti , Diehl Leah , Jennings-Coulibaly Alexis , Li Derek , Durning Patricia , Bashir Shazia , Markham Merry Jennifer , Rhoton-Vlasak Alice
Published: June 2023

e24038

Background: Women who are diagnosed with gynecologic cancer experience a significant level of distress and symptoms that impact their quality of life. Recently, there has been an emphasis on quality of life for oncology patients. Non-pharmacological interventions such as therapeutic horticulture (TH) have been linked with enriching individual lives. TH is defined as the engagement of a person in gardening and plant-based activities, facilitated by a professionally registered horticultural therapist, to achieve specific treatment goals. The purpose this study is two-fold: 1) to determine the impact of TH on quality of life and anxiety for gynecologic oncology patients and 2) to test the feasibility and acceptability of implementing a pilot TH program for this specific patient population. Methods: This was an IRB approved study. Individuals were recruited from the oncology clinic. Inclusion criteria included adult women, age 18 and over, who were diagnosed with gynecologic cancer. They were included in the study independent of what stage they were in their cancer treatment. The intervention included attending eight 1-hour group-based gardening sessions that were led by a professionally registered horticultural therapist at Wilmot Botanical Gardens. Self-report psychometric assessments were administered to assess anxiety and quality of life before and after the intervention. Results: Over one month, ten patients were interested in the study. Due to limitations in funding, only seven were able to partake in the study. Three participants were able to complete the study in its entirety by attending eight out of the twelve sessions. Four participants were unable to complete at least eight sessions due to scheduling conflicts: one completed seven sessions and three completed less than five sessions. Given that only three patients completed the intervention, quantitative measures are not included. In the focus group at the end of the study, the three participants described the TH as engaging and felt that they were more physically active and mentally at peace. They felt that the sessions brought camaraderie amongst each other regardless of the number of sessions attended. Conclusions: While our participant accrual was limited, the study was noted to be feasible and acceptable with the sessions being overall helpful for well-being. Given the results from this study, more funding has been established for recruiting a larger cohort in Fall of 2023.
First integrative oncology clinic in the Veteran Affairs (VA) Pittsburgh healthcare system.
Authors: Tan Jocelyn L , Rai Hema , Passero Vida Almario , Green Jeanne , Herman James G. , Genovese Dana , Harrold Lauri , Denk Lisa
Published: June 2023

e24041

Background: Integrative oncology (IO) is PROACTIVE and combines complementary with conventional care. The VA's comprehensive collection of integrative services is already in place. However, providers are often unaware of these, therefore veteran cancer patients don’t benefit from them. Prostate cancer is the most common cancer within the VA (31.8%), Aside from radiation/chemotherapy side effects (dry mouth, stomatitis, fatigue, neuropathy, gastrointestinal ) prostate cancer patients also have hormonal issues (hot flashes, low bone density, sexual dysfunction). Conventional treatments focus on symptoms (REACTIVE). Complementary and IO approaches are evidence-based toward specific treatment-related side effects. By educating and offering integrative approaches, we empower veterans to take charge of their health and well-being. Shifting our focus from treating only the disease to treating the entire patient, will improve health outcomes. Methods: Recruit 40 prostate cancer patients with fatigue, radiation-induced diarrhea, neuropathy, nausea, vomiting, anorexia, constipation, sexual dysfunction, and emotional issues(depression, anxiety, poor sleep, lack of energy). Identify/train providers to focus on concerning areas. Develop VA Personal Health Plans (PHP) to identify patients mission, aspiration, and purpose (MAP). Offer acupuncture, yoga, Reiki, TaiChi, meditation, biofeedback for headaches - Video Support group. Assessment tools. In late 2022, we reached our goal of 40 prostate cancer patients and opened clinic enrollment to patients of all cancer types. Results: The pilot IO clinic began in 2020, with 40 patients. In 2022, we expanded services to patients with other cancer types. Integrative options improved surgical outcomes, minimize chemotherapy /radiation side effects, boost morale, and optimize clinical outcomes. There is a high-interest level among oncology staff and patients. Resources are abundant but need organization and refinement to effectively present IO to our patients. Conclusions: There is huge potential for integrative oncology to improve the clinical, laboratory, and quality-of-life outcomes of cancer patients. We were able to construct a program within the Veteran Affairs, using existing integrative resources with high patient engagement. Currently, we plan to expand services to other VA sites nationwide.
Role of ketogenic diet in the management of cancer: A systematic review.
Authors: Chelikam Nikhila , Patel Urvish , Akella Sai Anusha , Ali Abdirazak , Lakhanpal Manisha Rakesh , Singh Aryak , Toor Varneet , Shivashankar Prashanth Gumpu , Shah Shlok Vimal , Lahori Simmy , Manjani Lokesh , Gujarathi Rahul , Manjani Divesh , Adiga Avinash , Kukreja Geetika
Published: June 2023

e24042

Background: Cancer is 2nd leading cause of death (1 in every 5) in the United States followed by heart disease. Use of ketogenic diet (KD)- high-fat & low-carbohydrate diet, allows fatty acids to become the obligatory source of cellular energy which can help in decreasing the tumor cell growth. Aim of this study was to evaluate role of KD in different types of cancer. Methods: We performed a systematic review using PRISMA protocol to identify articles describing the role of the ketogenic diet in cancer patients in PubMed. Keywords like cancer, neoplasm, tumor, KD, and intermittent fasting (IF) were used & filters like full text, English, human, observational studies, & clinical trials (CTs) were applied between 2018-2022. Results: Of the 362 studies after using filters only 22 studies were CTs. Of these 22, 12 studies were excluded & 10 studies were included in this study. [Table 1] We found CTs describing role of KD, IF or standard diet (SD) in brain cancer, non-metastasized rectal cancer, high-grade glioma, head and neck squamous cell carcinoma, locally advanced and metastatic breast cancer, ovarian and endometrial cancer. KD was describes as an accompanying measure for patients undergoing standard-of-care therapy that helps to improve the quality of life, survival & acceptable safety and tolerability. KD may augment the antitumor effects of classic chemotherapy and radiotherapy. Conclusions: Role of KD is described in depth, but majority RCT results were heterogeneous in nature to provide quantitative measures of survival timeline, outcomes, & recovery. Thus, more human prospective studies are warranted to evaluate the therapeutic effectiveness & safety of KD.[Table: see text]
A new model of cancer survivorship: Feasibility and findings of a survivorship-based primary care clinic led by a medical oncologist.
Authors: Yurkiewicz Ilana , Steele Natasha
Published: June 2023

e24043

Background: Since the Institute of Medicine published “From Cancer Patient to Cancer Survivor: Lost in Transition,” there has been widespread recognition of the role of primary care in providing long-term care for cancer survivors. However, many gaps remain as patients transition from oncology to primary care. We report on the findings of an innovative practice model in which a medical oncologist opened a primary care clinic to address survivorship-specific needs and ongoing primary care in one place. Methods: The clinic was housed in the primary care division of a large academic medical center. The physician is board certified in internal medicine, oncology, and hematology. Data were collected from when the clinic opened November 1, 2021 through January 31, 2023 via electronic chart review. Results: A total of 209 patients established care. Seventy-four percent were women, with a mean age 54, age range 19 to 89, and 24% adolescents and young adults aged 39 or younger. The most common cancer was breast (44%), followed by leukemia (12%) and lymphoma (10%). Thirty-two patients (15%) had undergone an allogeneic or autologous bone marrow transplant (BMT). Thirty-three patients (16%) had a hereditary cancer syndrome, including 11 with a BRCA mutation and 10 with a TP53 mutation. A majority (74%) were post treatment; 22% had active disease; and 3% were “previvors” with a genetic syndrome without a cancer diagnosis. Twenty-seven (13%) had more than one cancer. Most referrals came from medical oncology (36%), followed by self-referrals (29%) and hematology or BMT (11%). Most (74%) returned for at least one follow-up visit. Long-term and late effects were addressed in 87% and at least one other primary care problem was managed in 96%. These included cardiovascular risk (92%, with a new cardiovascular medication started in 31 patients), mental health (76%), bone health (47%), sexual health (22%), and fertility (19%). Secondary cancer screening was addressed in 93%, and four secondary cancers were diagnosed. Surveillance for the primary cancer was addressed in 86%, and seven recurrences were diagnosed. Conclusions: Given a growing need to care for cancer survivors and known challenges in the oncology to primary care pipeline, new models of comprehensive survivorship care are greatly needed. This study demonstrates the feasibility and high demand for a novel survivorship-based primary care clinic in which both ongoing survivorship needs and routine primary care are managed concurrently.[Table: see text]
Clinical use of quality of life data for treatment and survivorship in oncology.
Authors: Beutter Chantal N.L. , Vladimirova Dilyana , Martens Uwe Marc , Fegeler Christian
Published: June 2023

e24044

Background: Since cancer treatment and disease itself may cause chronic limitations, the challenge of reducing symptom burden during therapy and achieving good Quality of Life (QoL) for longevity with cancer becomes increasingly important. Research already shows that including QoL during treatment increases compliance, survivorship and outcome, but the transition of these concepts into regular care are mostly not implemented. Nevertheless, do regular measurements give a good insight to personal deviations and may enable a harmonious transition from clinical - to post treatment and into everyday life. Methods: For this research assessment of QoL was carried out within a registry study of gastrointestinal patients at the SLK Clinics Heilbronn (DRKS00018788). As a registry study, research is not bound to a fixed deadline, therefore we're still recruiting. First, we deployed a process for a continuous, digital measurement of QoL at clinical visits through the QLQ-C30. Parallel, a separate project implemented an app to measure QoL independently from home. Both ways, data is then structured to visualize the course of events for the identification of deviations or trends. Results: Up to now we included almost 100 patients with over 600 assessment points in our study. It could be shown that our process is applicable in the real world setting of clinical routine and accepted by patients. The study has been running for about 36 months and we were able to visualize QoL charts over several data collection points per patient. Trends within data indicate a relation of the clinical course to changes in QoL. Thus, a possible correlation of the decrease in tumor markers with an increase in QoL is shown. Also, progressions usually result in a significant decrease of QoL. Nevertheless, data also showed that one should be careful to relate the course exclusively to therapy or disease, since environmental influences such as injuries, infections or multimorbidity’s did also result in declines. Here, not only the interpretation of the overall QoL is important, but also the consideration of individual dimensions. Thereby specific limitations of how the patient experiences therapy or possible long-term consequences for survivors get more tangible. To better assess these factors, monitoring of QoL is necessary, not only at visits, but also at home. The developed app for assessing QoL independently was able to show that such a survey can be implemented and applied. Uniform data structure via HL7 FHIR ensures interoperability of the data for both systems. Conclusions: It could be shown that a standardized survey of QoL is possible both in clinical use and independently through patients at home. To close information gaps between clinical visits, both concepts should be merged next to enable an independent survey with a continuous measurement across all therapy stages. With that, adjustments or transitions in therapy could be tailored by limitations in a patients’ QoL.
Healthy lifestyle behaviors among a diverse population of early posttreatment adolescent and young adult (AYA) survivors participating in a virtual stress management program.
Authors: Venkataraman Vinayak , Markwart Michaela , Finkelstein-Fox Lucy , Temel Jennifer S. , Park Elyse R. , Perez Giselle Katiria
Published: June 2023

e24048

Background: Adolescent and young adults (AYA) cancer survivors have worse long-term physical health than survivors of adult cancers. Healthy lifestyle behaviors can maximize physical health and enhance quality of life. The National Comprehensive Cancer Network (NCCN) publishes survivorship guidelines for healthy behaviors; however, it is unclear if AYA survivors follow these recommendations. Methods: This is a secondary analysis of a waitlist-controlled trial of an adapted mind body stress management group program for AYA survivors recruited between 03/2019-09/2020. Participants completed self-report questionnaires assessing tobacco use, e-cigarette use, alcohol use, physical activity, and sleep quality both before and after completing the 8-week group program. Descriptive statistics were used to characterize the proportions of survivors meeting NCCN guidelines at time of enrollment. Results: Seventy-two AYA survivors participated in this study (mean age 24, 74% female, 60% Non-Hispanic White, 21% Hispanic, 4% Black, 53% hematologic malignancy, mean 1.6 years post-treatment).Table 1 summarizes NCCN guidelines and concordant behavior at enrollment. Most participants met guidelines for tobacco and e-cigarette use at study entry, with the majority reporting they abstained from using tobacco (85%) and e-cigarettes (90%). Only 28% reported abstaining from any alcohol use. Of those who consumed alcohol, most reported consuming < 3 drinks per day (83%), but 65% endorsed at least occasional binge drinking behavior ( > 5 drinks). Only 52% met guidelines for vigorous- or moderate- intensity activity (i.e. 75 and 150 minutes weekly, respectively). Specifically, participants reported a median of 47.5 minutes/week (IQR 0-120 min/week) of vigorous-intensity activity and 60 minutes/week (IQR 30-140) of moderate-intensity activity. Many experienced sleep concerns, with only 30% reporting good or very good sleep (i.e. > 4 on a 1 (very poor)-5 (very good) Likert scale). Conclusions: In a racially/ethnically diverse sample of AYA survivors, NCCN survivorship guideline concordance for healthy lifestyle was mixed. Of concern was that AYA survivors’ use of tobacco and e-cigs was similar to the general population. Furthermore, alcohol and physical activity recommendations were mostly not followed, and reported sleep quality was poor. These results highlight the need to better understand barriers and promote healthy lifestyles to optimize post-treatment outcomes. [Table: see text]
Perspectives about healthy eating and exercise among patients and providers at the safety-net Lyndon B. Johnson (LBJ) hospital oncology clinic.
Authors: Kizub Darya Aleksandrovna , Ramsey Margaret , Baum Miranda , Ma Hilary Y. , Patel Tejal Amar , Basen-Engquist Karen
Published: June 2023

e24055

Background: Previous studies have described barriers and facilitators of healthy eating and exercise among cancer patients, but none have done so in a primarily low-income minority population. Understanding the perspectives of patients and providers from safety net hospitals has important implications for optimizing diet and exercise counseling and referral strategies to bridge disparities in cancer care and outcomes. Methods: The population at LBJ hospital is majority Hispanic and Black that are uninsured or underinsured. We conducted semi-structured interviews with patients who were either undergoing or completed cancer treatment at LBJ, as well as with clinic providers, to compare perceived barriers and facilitators of healthy eating and exercise. Interviews were audio-recorded, transcribed, and analyzed via hybrid analysis. Results: Thirty-one patients were interviewed, including 20 (65%) survivors and 11 (35%) who were on active treatment. Twenty-one (68%) were female, 22 (71%) Black, 5 (16%) Hispanic, and 4 (13%) other. Twenty-one healthcare providers were interviewed, including 5 (24%) physicians, 5 (24%) nursing professionals, 4 (19%) dietitians, and 7 (33%) ancillary staff. Barriers to healthy diet and exercise for patients as perceived by providers included lack of knowledge (100%), low access (80%) due to financial difficulties, transportation issues, work and family responsibilities, and low motivation (76%). This resulted in reluctance to counsel patients about healthy living, in part due to anticipated low adherence to recommendations (33%). Most patients could name components of and thought they had a healthy diet (65%), but did not exercise enough (75%) due to cancer-related physical and mental health symptoms (68%). Patients recognized benefits of healthy eating and exercise during and after cancer treatment (32% each) and recalled recommendations from providers about healthy living (48%). Patients voiced high motivation to participate in healthy eating and exercise programming (84%) and follow their medical team’s recommendations (84%), so long as programming was convenient (29%) and included flexibility of multiple options (56%). Patients acknowledged resource-related barriers to healthy living but cited proximity to grocery stores and exercise facilities (84%), help from family in cooking meals (52%), and ability to walk outside or exercise with friends (13%). Conclusions: Despite multiple barriers of capacity, opportunity, and motivation to healthy eating and exercise, cancer patients in a safety-net hospital recognized the importance of healthy living, wanted to participate in such programs, and to get additional information or referrals from their medical team. Based on these results, ongoing studies are evaluating the implementation of referral pathways to healthy living programs for cancer patients at LBJ.
Effect of insulin resistance on CAC scores in cancer survivors.
Authors: Jacobi Nicole , Ortman Syndal Ann , Buda Lea , Duprez Daniel
Published: June 2023

e24056

Background: Many cancer (ca) survivors exhibit signs of insulin resistance (IR), an important risk factor for the development of coronary artery disease (CAD). Paramount in survivorship care is prevention of cardiovascular disease. Coronary artery calcium (CAC) scans offer a risk assessment of cardiovascular (CV) disease before cardiac damage has occurred. We investigated how IR affects CAC scores in cancer survivors. We hypothesized that CAC scores differ significantly between insulin-sensitive- and -resistant cancer survivors. Methods: We enrolled 90 cancer survivors of a large community hospital from March 2021 to January 2022 into this pilot study. Patients were subdivided into three groups: insulin-sensitive (IS), insulin-resistant/prediabetic and insulin-resistant/diabetic. Patients were tested for fasting insulin, -glucose, HgbA1c and lipids. Patients without evidence for prediabetes or diabetes also underwent an oral glucose tolerance test (oGTT). All patients received a CAC scan. Results: 32 patients were IS, 29 patients were IR/prediabetic and 29 patients were IR/diabetic. 17 CAC scans in the IS group, 6 CAC scans in the IR/prediabetic group and 5 CAC scans in the IR/diabetic group showed an Agatston score of 0. The p-value between the three groups was statistically significant ( p=0.005) where as the IR/prediabetic- and the IR/diabetic group did not differ statistically from each other. The mean MESA 10-year CHD risk with CAC was 7.8. There was a highly significant difference between the 3 groups: the IS group had a mean of 5.3, the IR/prediabetic group had a mean of 7.3, and the IR/diabetic group had a mean of 11.0 ( p < 0.001). The two IR groups did not differ statistically (p=0.076). Conclusions: Our study showed that IR including prediabetes significantly increases the MESA 10-yr. CHD Risk with CAC in cancer survivors. Survivors with IR also have less frequent zero CAC scores than insulin-sensitive survivors. Survivors disproportionately exhibit insulin resistance, partly due to the association of certain types of cancer with IR. This trial highlights the importance of screening survivors for IR. Survivors diagnosed with IR should be screened for CAD more frequently than the general population. CAC scans are an inexpensive and efficient way of screening asymptomatic cancer survivors for CAD.
Factors associated with long-term gastrointestinal toxicity in colorectal cancer survivors in the women’s health initiatives (WHI) study.
Authors: Han Claire , Reding Kerryn , Kalady Matthew , Yung Rachel Lynn , Paskett Electra
Published: June 2023

e24057

Background: Colorectal cancer (CRC) survivors often experience long-term symptom toxicity after cancer treatments. We described persistent gastrointestinal (GI) toxicity related to cancer and treatments in long-term CRC survivors and assessed the risk and life impact factors of GI toxicity. Methods: A cross-sectional study utilized data from the Women’s Health Initiative (WHI) Life and Longevity After Cancer (LILAC) study that recruited postmenopausal women. CRC survivors after cancer treatments were included (N = 413). Pearson correlations/A Chi-square test and multivariable linear regression models were used to identify risk and impact factors of GI toxicity. Results: 81% of CRC survivors experienced persistent GI toxicity. Bloating/gas was the most prevalent (54.2%) and severe, followed by constipation (34.1%), diarrhea (33.4%), and abdominal/pelvic pain (28.6%). Time since cancer diagnosis (< 5 years), advanced cancer stage, low income, high psychological distress, poor dietary habits and physical activity, and impaired life impact measures (health-related quality of life, daily life interferences, and body image) were significantly associated with several GI toxicities. Fatigue and sleep disturbance were the most significantly associated with long-term GI toxicity (Table 1). Abdominal/pelvic pain significantly influenced life impact measures. Conclusions: GI toxicities are highly prevalent among CRC survivors, specifically in patients with high psychological distress. A better understanding of the long-term GI toxicity in CRC survivors and identifying those more vulnerable may inform future directions for managing CRC survivorship. An individualized, multifaceted intervention is warranted to consider psychosocial support, lifestyle intervention, and physical rehabilitation. [Table: see text]
The safety, tolerability and efficacy of LP-10 in subjects with refractory moderate to severe hemorrhagic cystitis: Phase 2a multicenter dose escalation clinical trial.
Authors: Chancellor Michael , Breyer Benjamin , Joshi Shreyas S. , Smith Christopher , Kaufman Melissa , Okonski Janet , Hafron Jason
Published: June 2023

e24064

Background: Hemorrhagic Cystitis (HC), a rare but highly morbid disease for which there are currently no FDA approved treatments, can occur in cancer survivors including patients with prostate cancer, cervical/uterine cancer and colon cancer. Lipella Pharmaceuticals received orphan disease designation for HC, and recently completed a phase 2a clinical trial of LP-10 (intravesical tacrolimus) for the treatment of HC. Methods: The LP-10 Phase 2a clinical trial was a multi-center, dose-escalation study (clinicaltrials.gov: NCT01393223). The study recruited subjects with moderate to severe refractory HC. These subjects were treated with up to two courses of LP-10 intravesical bladder instillations (liposomal formulation of tacrolimus at 2 mg, 4 mg and 8 mg). Results: Fifteen subjects were screened (14 male and 1 female) and 13 enrolled. All enrolled subjects were male with mean age 67 (range 25-89 years old) with a history of prostate cancer (n = 9), bladder cancer (n = 2) and lymphoma (n = 2). Mean duration of HC was 4 years and ranged from 1-14 years. No subject discontinued treatment or were lost to follow-up. All subjects tolerated LP-10 instillations and completed the study without report of product related serious adverse events. 12 AEs were reported in 6 subjects. Pharmacokinetic analysis demonstrated short duration of low systemic uptake of tacrolimus. A dose response was noted with higher efficacy at both the 4mg and 8 mg dose groups. After LP-10 treatment, the number of cystoscopic bleeding sites and bladder ulcerations decreased and patients’ urinary symptoms improved. Conclusions: This first phase 2a study demonstrated safety and a signal of efficacy at intravesical tacrolimus (LP-10) doses of 4 mg and 8 mg for the treatment for HC, a rare and serious disease. Clinical trial information: NCT01393223 . [Table: see text]
Outcome of deep venous thrombosis and pulmonary embolism in COVID-19 cancer patients vs non-cancer patients.
Authors: Jones Can , Menchaca Kristina D. , Ostos Catherine , Elsheshtawi Mohamed , Velez-Quinones Virginia , Peles Shachar , Saeed Hayder
Published: June 2023

e24066

Background: COVID-19 is associated with an increased incidence of venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism (PE). Multiple mechanisms including COVID-19-induced endothelial dysfunction, cytokine storm, complement activation, and hypoxia lead to the activation of the coagulation cascade. Of note, VTE is the most common presentation of cancer-associated thrombosis. It is associated with worsened prognosis and mortality in both COVID-19 patients and cancer patients. Some studies indicated that comparing to COVID-19 non-cancer population, COVID-19 cancer patients have a higher risk of developing VTE. Methods: This retrospective cohort study identified 1,306 adult patients admitted to the tertiary medical center for COVID-19 treatment from 2020 to 2021, including 38 active cancer patients and 1268 non-cancer patients. Skin cancers were excluded. All patients received anticoagulant for VTE prophylaxis. The primary outcome of interest was the VTE incidence. Results: There was no significant difference in baseline demographics between groups. 35 non-cancer COVID-19 patients developed DVT (2.76%), while one patient had DVT in the cancer group (2.63%); for PE, 25 non-cancer patients were found to have PE (1.97%), while one cancer patient was diagnosed with PE (2.63%). There were no statistical differences in DVT and PE incidences between the COVID-19 cancer group and the non-cancer group during hospitalization. However, the cancer group was found to have older age (P < 0.001), higher D-dimer (P = 0.024) level, and more severe thrombocytopenia (P < 0.001). The COVID-19 cancer group revealed significantly higher in-hospital mortality (36.84%) comparing to the non-cancer group (14.98%) (P < 0.001). Conclusions: Our study revealed no differences in the incidence of PE and DVT between the COVID-19 cancer population and the COVID-19 non-cancer population; COVID-19 cancer patients experienced significantly higher mortality comparing to COVID-19 non-cancer patients. This highlights the importance of having larger-scale studies in the future to assess different outcomes in patients with malignancy and COVID-19.
Understanding cancer treatment decision making among cancer survivors.
Authors: Streck Brennan , Vo Jacqueline B. , Brandt Carolyn , Klein William , Han Paul , Ferrer Rebecca , Gillman Arielle Samantha
Published: June 2023

e24076

Background: Nearly 20% of U.S. cancer survivors develop late cardiovascular disease (CVD) as a result of cardiotoxic cancer treatments. Patients and providers may consider alternative treatment options to lower cardiotoxicity risk, which may present a trade-off between reducing relatively near-term relapse/recurrence vs. preventing long-term CVD. Patients’ decision-making processes (e.g., delay discounting, risk perceptions for CVD vs. cancer) may affect such choices. However, these decision-making factors are not well understood in this context; nor is their association with treatment selection. Methods: In a cross-sectional survey using the online survey vendor Prolific, we recruited 443 U.S. cancer survivors (any type.) Using logistic regression, we assessed how survivors’ risk perceptions (deliberative, affective, and intuitive) for cancer vs. CVD were associated with decisions between two hypothetical cancer treatments involving different risk tradeoffs: Treatment 1: 5% chance of near-term cancer recurrence & 10% chance of CVD; Treatment 2: 10% chance of near-term cancer recurrence & 5% chance of CVD. We explored effects of delay discounting by randomizing participants to information describing immediate vs. delayed (10 years post-treatment) development of CVD. Results: Survivors ( Mage = 48, range 18-93) were, on average, 10.8 years from diagnosis. More survivors ( 72% v. 28%) chose Treatment 1 (lower cancer recurrence risk but higher risk of cardiotoxicity) than Treatment 2 (lower risk of cardiotoxicity but higher risk of cancer recurrence) . Immediacy of CVD development (immediate vs. delayed) was not associated with treatment selection (p = 0.12.) Modeling separately, higher levels of affective risk perception (“worry”) about cancer, but not worry about CVD, was associated with increased odds of choosing Treatment 1 ( OR= 1.25, p= 0.014.). Modeled together, cancer worry was associated with increased odds, whereas CVD worry was associated with decreased odds, of choosing Treatment 1 ( OR-cancer= 1.35, p= 0.002; OR-CVD= 0.76, p= 0.011). Neither deliberative nor experiential risk perceptions were significantly associated with treatment choice. Conclusions: Cancer survivors were more likely to select treatment that minimizes cancer recurrence rather than comparative CVD—regardless of the described immediacy of cardiotoxicity. Further, treatment decision also depended upon both cancer- and CVD-related worry but not deliberative or experiential risk perceptions. Comparatively to CVD, cancer is often more affectively-laden, especially among cancer survivors. These results suggest that in treatment discussions, clinicians may need to address not only the probabilities of treatment outcomes, but patients’ relative worries about cancer and cardiotoxicity.
External validation of biomechanical computed tomography for fracture risk classification in metastatic hormone sensitive prostate cancer.
Authors: Lin John Kent , Hearn Caleb , Getzen Emily , Long Qi , Drell Helayne , Lee David , Keaveny Tony M. , Jayadevappa Ravishankar , Robinson Kyle William , Wong Yu-Ning , Maxwell Kara Noelle , Narayan Vivek , Haas Naomi B. , Takvorian Samuel U. , Bikle Daniel , Chiang Janet M. , Khan Amna N. , Rajapakse Chamith S , Morgans Alicia K. , Parikh Ravi Bharat
Published: June 2023

e24077

Background: For men with metastatic hormone-sensitive prostate cancer (mHSPC) on androgen deprivation therapy (ADT), guidelines recommend dual-energy X-ray absorptiometry (DXA) screening to identify fracture risk and benefit from antiresorptive therapy. However, only 8% of men with mHSPC receive routine DXA screening. Biomechanical computed tomography (BCT) is a radiomic technique that measures bone mineral density (BMD) and bone strength from routine staging and surveillance CT scans but has not been validated in mHSPC. Methods: This retrospective cohort study included 99 patients with incident mHSPC beginning ADT (2013-2020) at one academic (n = 70) and one tertiary VA medical center (n = 29) with CT abdomen/pelvis or PET/CT imaging at baseline (within 1 year prior to ADT initiation) and follow-up (1-2 years after ADT initiation). BCT-assessed BMD T-score and femoral strength were calculated from baseline and follow-up CT scans. We evaluated the association between BCT measures and subsequent pathologic and non-pathologic fractures within 3 years following mHSPC diagnosis. Results: Among 99 patients, mean age was 68 years, 48 (48.5%) were White, and 45 (45.4%) were Black. During median follow-up of 19 months, 23 (24%) developed a pathologic and 15 (15%) a non-pathologic fracture. BCT and DXA-assessed femoral-neck BMD T-score were strongly correlated (R2= 0.94, N = 23). Higher BCT-assessed baseline BMD (Odds Ratio [OR] 0.5, p = 0.03) and bone strength (OR 0.57, p = 0.02) were each associated with decreased pathologic fracture (Table). Neither BMD nor bone strength were significantly associated with non-pathologic fracture. BCT identified 10 (10%) men eligible for antiresorptive therapy by established BMD, strength, or FRAX criteria at ADT initiation, 4 (40%) of whom never received it by the end of follow-up. Between baseline and follow-up, both BMD (-0.27) and bone strength (-0.34) decreased among patients who did not receive antiresorptive therapy (n = 76), with no difference in longitudinal change between ADT alone vs with androgen receptor signaling inhibitors. Conclusions: In this diverse, multicenter cohort of men with mHSPC beginning ADT, BCT BMD assessed from routine CT scans strongly correlated with DXA-assessed BMD. BCT measurements predicted subsequent pathologic fracture and identified additional men who would benefit from antiresorptive therapy. BCT may provide a practical method to assess the role for anti-resorptive therapy in patients with mHSPC. [Table: see text]
NGAL and KIM-1 as early biomarkers of cisplatin-associated nephrotoxicity.
Authors: Chebotareva Natalia , Zhukova Lyudmila , Krasnova Tatyana , Grechukhina Katerina
Published: June 2023

e24080

Background: Cisplatin can cause renal injury in one-third of the patients. After the uptake by tubular renal cells cisplatin causes TNF-a immediate inflammation and death of tubular cell, ischemia and vascular damage on the kidney, which results in glomerular filtration rate (GFR) decrease (Toyuz et al, 2019). Serum creatinine is increased at the time of approximately 50% of nephrons are damaged. The identification of predictors and early markers of renal damage will make it possible to identify a high-risk group and monitor renal damage (Touyz, 2018). NGAL is activated immediately after ischemic or direct toxic damage to the kidneys in the distal segments of the nephron (Schmidt-Ott et al, 2007; Mishra). KIM-1 is an early marker of proximal tubule damage (Prasaja et al, 2015). Both NGAL and KIM-1 demonstrated their role of renal damage biomarkers in contrast-induced acute kidney injury. The goal of this study was to assess NGAL and KIM-1 as biomarkers of early nephrotoxicity induced by cisplatin and to assess their role as risk factors. Methods: The study included 50 patients who received cisplatin. Nephrotoxicity was determined as a decrease in GFR to < 60 ml/min/1.73 m2 at 8 weeks from the initiation of therapy. The levels of KIM-1 and NGAL in urine samples were determined by ELISA before treatment and after 1, 2, 4 and 8 weeks of treatment. To assess risk factors for nephrotoxicity, a logistic regression analysis was performed with the inclusion of primary clinical and laboratory parameters. ROC-analysis was used to assess sensitivity and specificity of markers. Results: The decrease of GFR less then < 60 ml/min/1.73 m2 at 8 weeks was observed in 11 (22%) of patients. There were no signs of increase of blood pressure in 8 weeks of observation. Serum creatinine increased clinically significant in 8 weeks after the start of therapy. The level of NGAL and KIM-1 rapidly increased in 1 week after the start of therapy (p < 0.001) which is shown in Table. The unfavorable predictor of nephrotoxicity was a 1-week increase of urine NGAL and KIM-1: OR 8.37; 95%CI 4.64-95.84; p = 0.001. Both NGAL and KIM-1 demonstrated high sensitivity, specificity and area under the curve (AUC) – both 0.69 as early biomarkers of nephrotoxicity assessed after 8 weeks from the start of therapy. Conclusions: An increase of KIM-1 and NGAL observed earlier then serum creatinine increase. Elevation in 1 week after the initiation of therapy can predict nephrotoxicity with high specificity and sensitivity. At the same time an early increase in the concentrations of KIM-1 and in the urine is the independent risk factors for cisplatin-induced nephrotoxicity. [Table: see text]
Immune checkpoint inhibitors (ICIs) with or without anti-angiogenic agents (AAAs) and cardiovascular toxicity: A meta-analysis.
Authors: Madonia Giorgio , Veccia Antonello , Berti Alvise , Caffo Orazio , Russo Antonio , Gori Stefania , Inno Alessandro
Published: June 2023

e24084

Background: ICIs have extended survival across many tumor types at the cost of immune-related adverse events (irAEs) that can involve any organ or system, including cardiovascular system. Emerging evidence suggest that ICIs may have a role in promoting the atherosclerotic plaque progression, thus leading to acute vascular events (AVEs) This may represent a concern when combining ICIs with other anti-cancer agents burdened by cardiovascular toxicity, such as anti-angiogenic agents (AAAs), that are associated with increased risk of hypertension (HTN) and AVEs. In the present meta-analysis, we aimed to evaluate the odds of adverse events (AEs), irAEs, HTN and AVEs with ICI+AAAs, as compared with AAAs alone. Methods: Phase III randomized controlled trials were identified by searching the MEDLINE/PubMed, Cochrane Library and ASCO Meeting abstracts, from inception until June 2022. Systematic review and metanalysis were conducted according to PRISMA guidelines. AEs, irAEs, HTN and AVEs were collected (main outcomes of this metanalysis), objective response rate (ORR) and progression free survival (PFS) were also collected (secondary outcomes). AVEs were defined as stroke, myocardial infarction, thrombotic events, pulmonary embolism. Severe AEs, irAE, HTNs and AVEs were defined as grade ≥3 according to the National Cancer Institute Common Terminology for Adverse Events (CTCAE) version 4.0 or 4.03, as reported in each trial. Results: Twelve trials with a total of 8124 patients (4159 in the experimental arms and 3965 in the control arms) were included in the meta-analysis. The addition of ICIs to AAAs did not increase the rate of AEs (any grade, OR 1.15, 95%CI 0.71-1.85; severe, OR 1.18, 95% CI 0.96-1.44). In contrast, the incidence of irAE was significantly higher in the ICIs+AAA- group versus AAAs (any grade: OR 1.97, 95%CI 1.21-3.21, p = 0.007; severe: OR 3.20, 95%CI1.41-7.29, p = 0.006), as expected. There was no difference in terms of any grade HTN between the 2 groups (OR 1.17, 95%CI 0.91-1.50, p > 0.05), but severe HTN was higher among patients treated with ICIs+AAAs as compared with those receiving AAAs alone (OR 1.24, 95%CI 1.01-1.53, p = 0.04). AVEs rates were low in both groups (2.2% and 1.9% for ICI+AAA and AAA alone, respectively). A subset analysis of trials specifically reporting AVEs did not show any increase in ICIs+AAAs versus AAAs alone (any grade: OR 1.21, 95%CI 0.68-2.16, p > 0.05; severe: OR 1.14, 95%CI 0.61-2.15, p > 0.05). Overall, the ORR and PFS were higher in the ICIs+AAAs group as compared to AAAs alone (OR 2.25, 95%CI 1.70-2.97, p < 0.001; OR 4.37, 95%CI 2.91-5.83, p < 0.001, respectively). Conclusions: The addition of ICIs to AAAs significantly increased the risk for irAEs and severe HTN, but not the risk for AVEs.