bluuebunny/crossref_metadata_2025 huggingface dataset:
A phase 1 dose-escalation/expansion clinical trial of mocetinostat in combination with vinorelbine in adolescents and young adults with refractory and/or recurrent rhabdomyosarcoma: Interim results.
Authors: Federman Noah , Crane Jacquelyn , Gonzales Amanda M , Arias Rubi , Baroudi Munther , Singh Arun S.
Published: June 2022

11553

Background: Rhabdomyosarcoma(RMS) is the most common soft tissue sarcoma in children. Relapsed/refractory(R/R) RMS has a poor outcome and remains an area of unmet need. Histone deacetylase (HDAC) inhibitors have been shown to have activity in preclinical models of RMS. Mocetinostat (Mirati Pharmaceuticals) is an investigational oral HDAC inhibitor, that targets HDACs 1, 2, 3 and 11. Mocetinostat displayed high activity in in vitro RMS cell lines, RMS xenograft models and exerted synergistic activity in combination with vinorelbine. We report early interim results of the Phase 1 trial of mocetinostat with vinorelbine in R/R RMS. Methods: An investigator initiated Phase 1,open-label, dose escalation/expansion clinical trial. A modified intent to treat approach is used for efficacy analysis for a target accrual of 20 subjects in the dose expansion cohort. Subjects with R/R RMS were age ≥ 18 years old(yo) for the phase 1 dose escalation cohort and ≥12 yo for the phase 1 dose expansion. Mocetinostat 40mg, 70mg or 90mg was taken orally 3 times weekly with vinorelbine 25mg/m2 IV on day 1,8, and 15 in 21 day cycles. Maximum tolerated dose of mocetinostat in the dose escalation phase was 40mg, which was selected for dose expansion. Subjects were treated until disease progression by RECIST 1.1 or unacceptable toxicity. Results: A total of 8(6 FOXO translocation(+), 1 (FOXO-), and 1 unknown) have been enrolled at time of submission. 5 in dose escalation cohort, and 3 in dose expansion. Median age was 19 yo(range 16-63), Median prior treatment regimens were 2(range 1-4). All patients had measurable metastatic disease. 6 of 8 subjects had prior exposure to vinorelbine in prior salvage chemotherapy or maintenance chemotherapy. As of 20JAN2022 safety cutoff, most common AEs (all grades) observed in 7 evaluable treated patients include neutropenia (n = 5), anemia(n = 5), and nausea(n = 4). The only grade 3 or 4 treatment related AEs were neutropenia, lymphopenia and anemia. Myelosuppression was transient, reversible and responsive to growth factors. No SAEs related to mocetinostat and/or vinorelbine have been reported. As of efficacy cutoff 20JAN2022, 7 of 8 patients are evaluable for response. 4 subjects had a partial response (PR), 2 subjects had stable disease (SD) and 1 subject had progressive disease for a clinical benefit rate of 86% (CR+PR+SD). Rapid responses were seen in the majority of patients at median of 1.5 months(mos). Of the 6 responders, 4 had duration of responses (DOR) > 6 mo with a median DOR of 8 mos (range 4-16mo). Conclusions: In this interim analysis, Mocetinostat plus vinorelbine shows high efficacy and acceptable safety profile in this heavily pretreated group of R/R RMS patients. This study is open to accrual and enrollment is ongoing. Clinical trial information: NCT04299113.
Prevalence of ultra-rare undifferentiated round cells sarcoma of bone and soft tissue after genomic classification.
Authors: Palmerini Emanuela , Righi Alberto , Sbaraglia Marta , Carretta Elisa , Dei Tos Angelo Paolo , Magagnoli GIovanna , Cesari Marilena , Paioli Anna , Longhi Alessandra , Hakim Rossella , Picci Piero , Maioli Margherita , Cocchi Stefania , Scotlandi Katia , Donati Davide Maria , Ibrahim Toni , Gambarotti Marco
Published: June 2022

11559

Background: Over the last decade, the category of undifferentiated round cell sarcomas (URCS), defined by the absence of Ewing sarcoma-associated translocations, has emerged. Aim of this study was to assess prevalence of each entity and outcome after genomic classification. Methods: Ewing sarcoma and other URCS diagnosed between 1920 and 2020 were reviewed. All URCS with available material were analyzed with FISH, RT-qPCR and/or Archer FusionPlex Sarcoma Panel. Demographic and treatment were collected. Survival was analyzed in patients with available follow-up. Results: 1995 cases identified, 20 cases lacked material for further genetic analysis and were excluded. 1975 cases were classified as follows: 1925 Ewing sarcomas (97.47%), 25 CIC-rearranged sarcomas (1.27%), 16 BCOR-CCNB3 rearranged sarcomas (0.81%), 2 EWSR1-NFATC2 sarcoma (0.1%), one each as CIC-LEUTX and FUS-NFATC2 rearranged sarcoma (0.05% each), and 5 as unclassified URCS (0.25%). A different presentation according to tumor type was shown in 43/50 ultra-rare tumors (Table). Forty-one/50 cases had available follow-up: 20/41 patients underwent surgery, 14/41 surgery+radiotherapy, 6 radiotherapy only, and no local treatment for 1 patient. Chemotherapy was administrated to 36/41 patients (Ewing sarcoma drugs in 16/22 CIC-DUX-4 and 8/11 BCOR-CCNB3; osteosarcoma drugs in 2/11 BCOR-CCNB3, and doxorubicin/ifosfamide in 2/22 CIC-DUX4 and 2/5 URCS; not specified in 6 cases). The 3-years overall survival (OS) was 32.7%f for CIC-rearranged sarcomas (75% in localize disease, 7,7% for the advanced disease, p 0.0084), 81.8% for BCOR-CCNB3 sarcomas (87.5% localized, 66.7% advanced; p 0.0734), and 60% for URCS (p 0.057). 1 patient with CIC-LEUTX sarcoma presenting with metastases died 13 months from diagnosis, 1 patient with FUS-NFATC2 and 1 with EWSR1-NFATC2 rearrenged sarcomas were alive without disease at 8 and 5 years from onset. Conclusions: Prevalence of URCS characterized by a combination of morphologic observation ad molecular techniques is provided. The majority of the cases underwent surgery or surgery combined with radiotherapy, and Ewing-like chemotherapy. The survival difference among different entities underscores the need of accurate subclassification of round cell sarcomas. Novel drugs for CIC-DUX-4 sarcomas presenting with metastases are needed. [Table: see text]
Oral minoxidil for the treatment of late alopecia in cancer survivors.
Authors: Kuo Alyce Mei-Shiuan , Reingold Rachel E. , Ketosugbo Kwami , Pan Alexander , Dusza Stephen W , Kraehenbuehl Lukas , Gajria Devika , Lake Diana E , Bromberg Jacqueline , Goldfarb Shari Beth , Traina Tiffany A. , Fornier Monica N. , Gucalp Ayca , Dauscher Megan , Markova Alina , Lacouture Mario E.
Published: June 2022

12022

Background: Late alopecia is defined as incomplete hair regrowth > 6 months following cytotoxic chemotherapy or from initiation of endocrine therapy. It has been reported in up to 25-30% of cancer survivors and is associated with decreased quality of life and reduced dose intensity of cancer therapies. Minoxidil is an aminopyridine potassium channel opener, resulting in vasodilation and premature entry of resting hair follicles into the anagen (growth) phase and increase in hair follicle size. This study aims to assess clinical outcomes and adverse events of oral minoxidil for the treatment of cancer therapy-related late alopecia. Methods: We retrospectively assessed all women with late alopecia treated with oral minoxidil (1.25 mg daily) evaluated at an oncodermatology referral program between 1/2018-5/2021. Outcomes were assessed by standardized photography (4 views) and trichoscopy (HairMetrix, Canfield Scientific, Inc.). Trichoscopy recorded hair density (hair count/cm2) and hair thickness (shaft diameter) at uniform frontal and occipital target areas (12 and 36 cm midline from the glabella, respectively). Adverse events were recorded and graded using CTCAE v5.0. Descriptive statistics were used to summarize the patient demographics and clinical characteristics. Changes in trichoscopy measurements from baseline to follow-up were estimated using paired t-tests. Results: Two hundred and sixteen patients (mean age 57.8±13.7) were included for analysis. Thirty-one (14%) received chemotherapy alone, 65 (30%) endocrine monotherapy, and 120 (56%) chemotherapy followed by endocrine therapy. The majority of patients (n = 170, 79.1%) had a history of breast cancer. Standardized photography assessments (n = 119) after a median of 105 days (IQR = 70) on oral minoxidil revealed clinical improvement in 88 (74%). Trichoscopy assessments (n = 42) after a median of 91 days (IQR = 126) demonstrated increased frontal hair density (124.2 vs 153.2 hairs/cm2, p = 0.008) and occipital hair density (100.3 vs 123.5 hairs/cm2, p = 0.004). There was no statistically significant difference in average frontal or occipital hair thickness (69.3 vs 67.3 μm, p = 0.22, and 70.3 vs 69.9 μm, p = 0.84, respectively). No patients reported discontinuation of oral minoxidil due to adverse effects. Conclusions: Oral minoxidil may benefit both frontal and occipital late alopecia in cancer survivors treated with cytotoxic and/or endocrine therapy. This regimen was well tolerated by patients. Prospective, controlled studies are needed to confirm these observations.
Patients with cancer symptom and physical function reporting by caregivers as predictors of adverse clinical outcomes.
Authors: Neeman Elad , Yunis Reem , Kubo Ai , Aghaee Sara , Shieh Jennifer , Veuthey Tess L , Fonda Stephanie Jo , Liu Raymond , Oakley-Girvan Ingrid
Published: June 2022

12026

Background: Informal caregivers are essential partners in the delivery of cancer care, and often can accurately identify and report symptoms and physical function of the patients they care for. We assessed whether such reporting by caregivers is predictive of adverse patient outcomes. Methods: In this prospective study, adult solid cancer patients on active intravenous systemic therapies and their informal caregivers were recruited from 18 Kaiser Permanente Northern California cancer centers. Using a study mobile app (TOGETHERCare), caregivers completed weekly surveys for 4 weeks, which were based on normalized NIH-PROMIS scores to report patients’ physical function and PRO-CTCAE to report patients’ symptoms. Patients’ adverse clinical outcomes were abstracted from the medical record and included: emergency department (ED) visits or hospitalizations, grade 3-4 adverse events (AEs), and treatment delays, up to 1 month following the 4-week study period, as well as mortality and hospice referrals up to 6 months following the study period. Simple univariate logistic regressions were used to correlate caregiver reports (either at baseline or most proximal preceding an adverse outcome) with mortality and hospice referrals, and quasi-Poisson regressions were used for the other adverse outcome measures. Results: Fifty-four patient-caregiver dyads were enrolled, and 52 were included in this analysis. A third of patients had breast cancer and almost 75% had stage 3 or 4 disease. Caregivers predominantly identified as male (61.5%), spouse/partner (76.9%), and non-Hispanic White (63.5%). At least one adverse outcome was experienced by 36.5% of the patients. Caregiver-reported PRO-CTCAE consistently predicted ED/hospitalizations and mortality, and caregiver-reported PROMIS scores predicted hospice referrals (see Table). Conclusions: The results suggest that caregiver reporting of patients’ symptoms and physical function could help provide early predictions of adverse patient outcomes.[Table: see text]
Financial stress and burden among caregivers of cancer survivors in the United States.
Authors: Theodoropoulos Nicholas , Xie Hui , Wang Qian , Li Yannan , Wen Chi
Published: June 2022

12027

Background: United States caregivers perform annual services equating to nearly $500 billion, with three-quarters of family caregivers utilizing personal funds. Nearly a third of all caregivers of cancer survivors report using all or most of their savings to contribute to the cost of cancer care. Prior studies indicate the duration of caregiving is associated with an increase in caregiving burden. This study aims to further describe the financial stress and burden in relation to caregiving duration for people who provide care to cancer survivors. Methods: A retrospective cross-sectional study was conducted using the 2015 and 2020 National Alliance for Caregiving and American Association of Retired Persons survey data. Multivariable logistic regressions were used to examine differences in reporting financial stress between various racial/ethnic groups while adjusting for education, income, and employment. Results: A total of 2,998 caregivers were included, where 208 of them were caring for cancer patients. Caregivers of cancer patients who provided care > 21 hours/week were statistically more likely to be less educated, lower income, single, and unemployed compared to those who provided < 21 hours/week. Caregiving for > 21 hours/week compared to < 21 hours/week is associated with being more likely to report communicating with healthcare professionals about a recipient's care (87.7% vs. 75.9%; p = 0.038). It is borderline significant that caregivers who provided care for > 21 hours/week were more likely to advocate for recipients (68.7% vs. 56.8%; p = 0.086) and monitor condition severity to adjust care needs (84.9% vs. 70.7%; p = 0.100). After controlling for confounders (education, income, and employment), Non-Hispanic Black (odds ratio (OR) = 1.30; 95% CI: 1.02-1.65), Hispanic (OR = 1.39; 95% CI: 1.02-1.89), and Asian (OR = 1.51; 95% CI: 1.02-2.24) cancer caregivers had increased odds of reporting increased financial stress compared to Non-Hispanic White caregivers. Conclusions: Longer duration of caregiving to cancer survivors is associated with a greater burden for caregivers. Financial stress disparities related to caregiving exist between racial/ethnic groups, with non-white caregivers being more likely to report increased financial strain. Special financial programs are needed to assist caregivers of cancer survivors, a growing but understudied population.
Early patient-reported outcomes are a promising predictive factor of cancer progress and outcome in older patients: The EPROFECY study.
Authors: Helissey Carole , Riviere Clémentine , Parnot Charles , Duverger Claire , Becheriat Selma , Vuagnat Perrine , Schernberg Antoine , Picchi Hugo , Le Roy Audrey , Vanquaethem Hélène , Brureau Laurent
Published: June 2022

12045

Background: Contrary to commonly-held beliefs, older patients (OPs, aged 70 or more) in oncology are compliant with the use of a telemonitoring digital platform. Such a tool allows the medical team to gain detailed knowledge of the tolerance profile of patients, and help monitor and maintain their quality of life, which is a particularly important goal for older patients. The EPROFECY study assesses the predictive power of the patient health status in the first month of treatment, evaluated with the digital telemonitoring platform Cureety, on survival. Methods: This prospective study was conducted at the Military Hospital Bégin on OPs. Patients were allowed to respond to a symptomatology questionnaire based on CTCAE v.5.0, personalized to their pathology and treatment. An algorithm evaluated the patient status based on reported adverse events: correct (A), compromised (B), to be monitored (C) and critical state (D). For A/B (good health status), the patient received therapeutic advice to help manage each of the reported adverse events. For C/D (poor health status), the patient was invited to call the hospital. To assess the early tolerance of patience to their treatments, we determined the health status in the 1st month after initiation of treatment, which was classified as “Good health” (GH, majority of A/B reports) or “Poor health” (PH, majority of C/D reports). The primary endpoint was to assess if the first-month tolerance is a predictive factor of progression free-survival (PFS). The secondary endpoint was to assess if the first-month tolerance is a predictive factor of overall survival (OS). Results: Sixty-one patients were enrolled between July 1st, 2020 and September 30th, 2021. The median age was 78.0 years (range 70.0 – 99.0), with 81% presenting a metastatic stage, and the most represented cancer being prostate cancer. The median follow-up was 8.2 months. Overall, 2299 ePRO were completed, 89% (n= 2036) corresponding to a "correct" or a "compromised" state and only 11% (n=263) corresponding to a state "to be monitored" or "critical". Based on the first month of questionnaires, 62% of the patients were classified in the GH group, and 38% in the PH group. The PFS ratio at 6 months was 64.6 % in GH vs 23.4 % in PH (HR = 0.1980, 95% CI = 0.04431–0.8845, p = 0.0339). The OS ratio at 6 months was 100% in GH versus 95.5 % in PH (HR: 0.69, 95 % CI = 0.06 – 8.29, p = 0.77). Conclusions: This is the first study that assesses the use of PRO-based tolerance as a predictive factor of treatment response in older individuals. We demonstrated here a significant 80% reduction in the risk of progression in OPs that exhibited a good first-month tolerance. This suggests that e-PRO follow-up might be an effective predictor of response and a tool to treatment plan.
Cardiovascular disease in testicular cancer survivors: Identification of risk factors and impact on quality of life.
Authors: Lubberts Sjoukje , Groot Harmke J. , De Wit Ronald , Mulder Sasja F. , Witjes Alfred Alfred , Kerst Jan M. , Groenewegen Gerard , Lefrandt Joop D. , Van Leeuwen Flora , Nuver Janine , Schaapveld Michael , Gietema Jourik A.
Published: June 2022

12070

Background: Testicular cancer (TC) treatment has been associated with cardiovascular disease (CVD) development. To facilitate development of preventive strategies, this study assessed risk factors associated with CVD in TC survivors. Methods: Incidence of coronary artery disease, myocardial infarction and heart failure was assessed in a multicenter cohort comprising 4,748 TC survivors treated at ages of 12-50 years between 1976-2007. Patients who developed CVD and a random sample from the cohort received a questionnaire on cardiovascular risk factors (CVRF) and quality of life (QoL, measured with SF-36). A subgroup (n=304) of responders in the cohort additionally underwent clinical evaluation of CVRF. Results: After a median follow-up of 16 years, 272 patients developed CVD. Compared to orchidectomy only, platinum-based chemotherapy was associated with increased CVD risk (Hazard Ratio (HR) 1.8, 95% Confidence Interval(CI) 1.3-2.5). CVD risk was increased among patients who were obese or a smoker at diagnosis (HR 4.7, 95%CI 2.4-9.3 and HR 1.5, 95%CI 1.1-2.2, respectively) and patients with Raynaud's phenomenon (HR 1.9, 95%CI 1.1-3.6) or a family history of CVD (HR 2.7, 95%CI 1.6-4.5). TC survivors with CVD reported inferior QoL on physical domains (table). In TC survivors who underwent clinical evaluation for CVRF (median age at assessment 51 years), 86% had dyslipidemia, 50% hypertension and 35% metabolic syndrome, irrespective of treatment. Conclusions: TC survivors treated with platinum-based chemotherapy, who were obese or smoking at diagnosis, had family history of CVD and who developed Raynaud’s phenomenon are at risk to develop CVD, which affects QoL. Many TC survivors carry undetected CVRF. We advocate early lifestyle adjustments and lifelong follow-up with low-threshold treatment of CVRF, especially in obese and smoking patients treated with platinum-based chemotherapy. [Table: see text]
Polymorphism rs4673 and plasma paraoxonase 1 level for prediction and early diagnosis of anthracycline-mediated cardiotoxicity in patients with breast cancer.
Authors: Gvaldin Dmitry Yu. , Timoshkina Natalya N. , Vashchenko Larisa N. , Ausheva Tatiana V. , Sagakyants Aleksandr B. , Shulgina Oksana G. , Dashkova Irina R. , Kechedzhieva Emma E. , Vladimirova Liubov Yu
Published: June 2022

12077

Background: Anthracyclines are highly effective chemotherapeutic agents, used for a wide variety of malignancies. Despite their antitumor efficacy there is a risk of cardiotoxic manifestations that reduce the time and quality of life of patients. The purpose was to study the effectiveness of molecular genetic tests based on rs4673 CYBA genotyping (c.242C > T) and measurement of plasma paraoxonase 1 (PON1) level in patients with breast cancer (BC) for predicting and diagnosing anthracycline-mediated cardiotoxicity (AMC). Methods: The study included 256 Caucasian patients (median age - 55 years) with a diagnosis of breast cancer normal cardiovascular system parameters at baseline, who were treated with anthracyclines in 2019-2020. For rs4673 genotyping, DNA was extracted from the blood by using DNA-sorb-B (AmpliSens, Russia). HRM-PCR was performed on a CFX96 amplifier (Bio-Rad, USA). The presence of polymorphism was confirmed by the Sanger method on a Genetic Analyzer 3500 (ABI, USA). The concentration of PON1 in blood plasma was measured at baseline and after 4 course of chemotherapy with anthracyclines using ELISA kits (Cloud-Clone Corp., China/USA). Results: During the follow-up period 21 (8.2%) patients developed signs of subacute (changes developed within several weeks after the last course of therapy) or early chronic AMC (changes developed within a year after completion of anthracycline therapy). In the group of patients without AMC the frequency of the minor allele rs4673 (c.214C > T CYBA) was 0.38, the frequency of genotypes C/C was 0.4, C/T - 0.43, and T/T - 0.17. The risk of AMC increased by 6.49 times in the presence of the rs4673 polymorphic allele (p = 0.002). The area under the ROC curve of the test based on rs4673 genotyping was 71.9%. The concentration of PON1 after the 4 courses of chemotherapy increased by 19.57% in the group of patients without cardiotoxic manifestations (p = 0.018) and in the group of patients with AMC by 20.23% (p = 0.007) as compared to the initial level. Besides, after 4 courses of chemotherapy the PON1 level was higher in patients with AMC by 25.08% (p = 0.026) than in patients without cardiovascular complications. The sensitivity of the test based on the measurement of the PON1 level in the blood plasma after 4 courses of chemotherapy was 100%, the specificity was 70.8% with a cut-off value of 2.9 ng/ml. Conclusions: This study has showed that genotyping of patients for the rs4673 polymorphism allows pre-stratification of the risk group white determination of the PON1 level in blood plasma after 4 courses of chemotherapy gives the opportunity to identify patients with AMC and promptly correct the chosen treatment.
Hair Safe Study: Effects of scalp cooling on hair preservation and hair regrowth in breast cancer therapy—A prospective interventional study.
Authors: Brunner Christine , Kofler Ricarda , Egle Daniel , Wieser Verena , Ritter Magdalena , Abdel Azim Samira , Lehmann Marlene , Emmelheinz Miriam Elisabeth , Marth Christian
Published: June 2022

12093

Background: Chemotherapy (CT) is a frequent and well established treatment in women with breast and gynecological tumors. Alopecia is one of the most common side effects of CT seriously impairing patient quality of life and body image. While other CT associated side effects can be controlled by supportive treatment strategy, adequate preventive measures for alopecia have been lacking. New evidence supports the efficacy of scalp cooling for alopecia prevention during CT. The aim of this study was to investigate preventive scalp cooling (SC) for chemotherapy-induced-alopecia in breast cancer patients undergoing standard adjuvant or palliative chemotherapy. We also analysed the impact of SC on hair regrowth after chemotherapy-induced-alopecia. Methods: This was a non-randomized, 2-arm interventional study conducted at the Department of Obstetrics and Gynecology, Medical University Innsbruck. Breast cancer patients receiving any chemotherapy associated with alopecia (i.e. taxane or anthracycline-based chemotherapy) were allocated either to an intervention group receiving SC or to a control group (no SC). SC during chemotherapy was applied by the Paxman scalp cooling system. The primary endpoint was hair preservation (HP) which was assessed by experts and patients using the CTCAE score and analysed during and after completion of chemotherapy. The secondary endpoint was hair regrowth (HR) after 3 and 6 to 9 months post chemotherapy. Results: The study population included 128 patients. The majority, namely 88 (69%) patients were assigned to the intervention group (CAP) and received SC, 40 patients were allocated to the control group (NCAP). HP was significantly higher in the group receiving SC than in the NCAP by patients’ self-evaluation (24% vs. 0%; P = 0.001) and experts’ assessment (72% vs. 0%, P ≤ 0.001). HR was comparable between both groups. Using the patients’ evaluation 50% of patients with taxane monotherapy had a grade 1 alopecia compared to 17% of patients with an anthracycline-taxane CT (50% vs 17%, P = 0.018). Drop-out rate was 13% in CAP and 5% in NCAP group. Main reasons for drop-out were hair loss and patients’ requests. Conclusions: Our study demonstrates that SCsignificantly reduced or avoided chemotherapy-induced-alopecia in breast cancer patients undergoing chemotherapy, especially in patients who received taxane-monotherapy. SC was a safe procedure without severe adverse events. Therefore, SC can be highly beneficial for patients receiving specific chemotherapy and the option should be made available to as many patients as possible. No significant effect was noted regarding regrowth after chemotherapy in the SC group.
Physical performance limitations and participation restrictions among cancer survivors: A population-based study from NHANES data 2015-2018.
Authors: Myers Samantha A. , Finch Emily R , Ness Kirsten K. , Campbell Kristin L.
Published: June 2022

12096

Background: Anti-cancer therapies have improved survival outcomes in cancer survivors; however, therapy-related toxicities may impact organ structure and function and interfere with physical performance and participation in life roles. This analysis aimed to estimate the prevalence of physical performance limitations (PL) and participation restrictions (PR) among recent (< 5 years since diagnosis), and long-term (≥ 5 years) cancer survivors. Methods: Data from the 2015-2018 National Health and Nutrition Examination Survey (NHANES) were analyzed using multivariable logistic regression, accounting for age, sex, race, and income, and incorporating survey sampling methodology. Odds ratios compared proportions of PL and PR among 663 (weighted population estimate 14,319,219) recent and 341 (weighted population estimate 7,261,088) long-term survivors, and 10,284 (weighted population estimate 215,042,155) persons with no reported cancer history. Two-sided two sample z-tests were used to compare proportions to a previous publication of data from 1999-2002 NHANES data. Results: Physical performance limitations were 1.5-1.7 times (63% vs 29%) and PR 1.5-1.6 times (38% vs 18%) more prevalent in cancer survivors than in those with no cancer history. Long-term cancer diagnosis was associated with increased prevalence of PL and PR, particularly in survivors aged 20-39 years. Proportions increased by 7% for PL and by 10% for PR compared to 1999-2002 values (p-values <0.001). Conclusions: Over 60% of cancer survivors reported PL and nearly 40% reported PR. Despite an interim increase in evidence of the benefits of exercise to manage therapy-related toxicities, these values are a significant increase when compared to 1999-2002 NHANES data. Targeted education for providers and exercise interventions aimed to improve physical function and performance in early cancer survivors should be considered to address the physical sequelae from anti-cancer therapies. [Table: see text]
Phase 2, randomized, double-blind trial of EC-18 versus placebo to mitigate the development and time course of oral mucositis from concomitant chemoradiation for head and neck cancer.
Authors: Henson Christina , Clayburgh Daniel , Lee Arielle Shebay , Wong Deborah J.L. , Kudrimoti Mahesh R. , Adkins Douglas , Lee Steve P. , Kalman Noah , Oppelt Peter John , Rao Krishna A. , Park Ji Sun , Oh Sookyung , Kim Koeun , Yoon Sun Young , Sohn Ki Young , Sonis Stephen T.
Published: June 2022

12106

Background: Oral mucositis (OM) is a debilitating side effect of concomitant chemoradiotherapy (CRT) for head and neck cancer (HNC). EC-18 may effectively mitigate OM by minimizing the CRT-induced innate immune response. This Phase II, 2-stage trial evaluated safety, tolerability, and efficacy of EC-18 in reducing the duration, incidence, and trajectory of severe OM (SOM) in HNC patients. Methods: Patients (n = 105) with pathologically confirmed oral cavity, oropharynx, hypopharynx, or nasopharynx squamous cell cancers who received intensity-modulated radiation therapy (IMRT; with ≥ 55 Gy on ≥ 2 oral sites) and weekly or tri-weekly cisplatin were studied. In Stage 1, 24 patients were randomized (n = 6 per arm) to receive 500, 1000, or 2000 mg of EC-18, or placebo. Following independent Data Safety Monitoring Board review, 81 patients in Stage 2 received EC-18 2000 mg (n = 41) or placebo (n = 40) throughout CRT. WHO OM grade was assessed twice weekly during IMRT and then once weekly for up to 6 weeks post-IMRT. The primary efficacy endpoint was duration of SOM during the active and short-term follow-up (STFU) periods in the compliant per-protocol population (PP). Much of Stage 2 was conducted during peak periods of the COVID-19 pandemic which measurably impacted patient compliance relative to test medication dosing and planned radiation. Consequently, to assess efficacy most accurately, the PP population was analyzed (with at least 4 weeks of study drug dosing, minimum cumulative radiation of 55 Gy, 80% study drug compliance in the first 28 days of dosing, and without using not-allowed-therapy). Results: Patient demographics and baseline characteristics were balanced between groups. Adverse events (AEs) were comparable amongst cohorts without drug-related severe AEs. In the PP, the median duration of SOM from baseline through STFU was 0 day in the EC-18 group (n = 22) v 13.5 days in the placebo group (n = 20). SOM incidence through STFU (45.5% v 70%) and opioid use (time to onset: 32.3 v 26.0 days; and duration: 32.8 v 37.5 days) favored EC-18 v placebo. Results of the covariates analyses suggested that EC-18 favorably impacted SOM incidence in patients who experienced SOM treated with weekly low-dose cisplatin (n = 26; 37.5% v placebo 70.0%) and HPV+ tumors (n = 29; 35.3% v placebo 66.7%; Table). One-year long-term follow-up for tumor outcomes is ongoing. Conclusions: EC-18 safely mitigated the development and the time course of SOM in CRT-treated HNC patients. In addition, EC-18 may provide substantial benefits to subpopulations of HPV+ HNC patients treated with low dose cisplatin. Clinical trial information: NCT03200340. [Table: see text]
Efficacy and safety of SER-109, an investigational microbiome therapeutic for recurrent clostridioides difficile infection: Data from ECOSPOR III, a phase 3 randomized trial.
Authors: Paskovaty Alla , Berenson Charles S. , Louie Thomas J. , Wang Elaine , Lombardi David A. , von Moltke Lisa
Published: June 2022

12113

Background: Patients with malignancies are at increased risk for recurrent Clostridioides difficile infection (rCDI) due to their immunosuppressed state and frequent exposure to antibiotics and chemotherapy. These factors disrupt the gut microbiome creating an environment conducive to C. difficile colonization. Patients with cancer have higher rates of rCDI and worse outcomes than those without malignancy. SER-109, an investigational microbiome therapeutic, was superior to placebo in reducing rCDI at 8 weeks compared with placebo (12% vs 40%, respectively) in ECOSPOR III, a Phase 3 randomized, double-blind trial of subjects with a history of rCDI [NEJM 2022; 386:220-9]. Here, we report secondary endpoints of rCDI rates at 4, 12 and 24 weeks. Methods: Adults with rCDI (≥3 episodes in 12 months) were screened at 56 US/Canadian sites. After standard-of-care antibiotics (vancomycin or fidaxomicin per investigator discretion), subjects were randomized 1:1 to SER-109 (4 capsules x 3 days) or matching placebo. The primary endpoint was rCDI (recurrent toxin + diarrhea requiring treatment) at 8 weeks; secondary endpoints included rCDI at 4, 12 and 24 weeks. Safety was evaluated through week 24. Results: 281 subjects were screened and 182 (intention-to-treat population; ITT) were randomized (59.9% female; mean age 65.5 years). The most common comorbidities were respiratory disease (36.3%) and cardiovascular disease (32.4%). A total of 28.6% and 18.1% had a history of immunocompromise and malignancy, respectively. Significantly fewer SER-109 vs. placebo treated subjects had rCDI posttreatment compared with placebo recipients at Weeks 4, 8, 12 and 24 (Table). The absolute risk reduction between placebo and SER-109 arms ranged from 22.1% to 28.3% across the 4 timepoints. The safety profile of SER-109 through week 24 was comparable to placebo. Most adverse events (AEs) were mild to moderate gastrointestinal occurrences. More placebo-treated vs SER-109-treated subjects experienced serious AEs through week 8, while comparable proportions of subjects in both arms reported serious AEs from 8 through 24 weeks. Conclusions: In this population of subjects with comorbidities, including malignancy and immunosuppression, SER-109 significantly reduced rCDI rates through week 24 with an observed safety profile comparable to placebo. Clinical trial information: NCT03183128. [Table: see text]
Acupuncture for hot flashes in hormone receptor-positive breast cancer, a pooled analysis of individual patient data from parallel randomized trials.
Authors: Lu Weidong , Giobbie-Hurder Anita , Tanasijevic Anna , Baedorf Kassis Sylvia , Park Sung Hwan , Jeong Young Ju , Shin Im Hee , Yao Chang , Jung Hyun Jung , Zhu Zhiyuan , Bao Chao , Yang EunMee , Bierer Barbara E , Ligibel Jennifer A.
Published: June 2022

12124

Background: Hot flashes are a common side effect of endocrine therapy in breast cancer patients (pts). In a coordinated multinational study, we evaluated the impact of acupuncture on hot flashes and related symptoms in hormone receptor-positive breast cancer pts undergoing adjuvant endocrine therapy in the USA, China, and South Korea. Methods: Parallel randomized trials were conducted at three sites: Dana-Farber Cancer Institute, USA; Jiangsu Hospital of Traditional Chinese Medicine, China; and Daegu Catholic University Medical Center, Republic of Korea, using the same inclusion/exclusion criteria, randomization, and measures. Breast cancer pts receiving adjuvant endocrine therapy and having ≥14 hot flashes per week were randomized equally to acupuncture (A) or usual care (UC); randomization was stratified by number of hot flashes per day (2-6 or 7+). Pts in arm A received a standardized acupuncture protocol twice per week for 10 weeks; pts in the UC arm received usual care. Symptoms were assessed at baseline and week 10. The primary endpoint was change in the Endocrine Symptom Subscale (ESS) of the Functional Assessment of Cancer Therapy-Endocrine Systems (FACT-ES). Secondary endpoints included changes in the FACT-Breast (FACT-B) and Daily Hot Flash Score (DHFS), a measure incorporating hot flash frequency and severity. Target enrollment was 160 pts (USA 80, China 40, Korea 40) providing 84% power to detect a clinically meaningful change in the ESS. Analyses were intention-to-treat. A pooled analysis of individual patient data was performed using linear models adjusted for site and baseline number of hot flashes. Results: Between Jan. 2019 and June 2021, 158 female pts with stage 0-III breast cancer were randomized from the USA (n=78), China (n=40), and South Korea (n=40). Median age was 48 years (range: 25 to 73). At baseline, pts reported similar numbers of hot flashes between study arms (6.2± 4.3 vs. 6.5± 3.8 per day). At week 10, pts in arm A reported statistically significant improvements in ESS score, FACT-B total score and DHFS compared with the UC arm (Table). The reduction in the DHFS from baseline in arm A was 53%. There were no serious adverse events. Conclusions: Acupuncture led to statistically and clinically meaningful improvements in hot flashes, endocrine symptoms, and breast cancer-specific quality of life in women undergoing adjuvant hormonal therapy for breast cancer in the USA, China and South Korea. Clinical trial information: NCT00797732, ChiCTR2100045888, KCT0003618. [Table: see text]
Association between the Affordable Care Act Medicaid expansion and survival in young adults newly diagnosed with cancer.
Authors: Ji Xu , Shi Kewei , Castellino Sharon M. , Mertens Ann C. , Zhao Jingxuan , Yabroff K. Robin , Han Xuesong
Published: June 2022

1502

Background: Medicaid expansion through the Affordable Care Act (ACA), implemented by 26 states in January 2014 and 13 more states in later years, has been shown to improve insurance coverage and early diagnosis of cancer in young adults (YAs). Little is known about whether these improvements translate to a survival benefit in this population. We evaluated the association between the ACA Medicaid expansion and 2-year overall survival among YAs newly diagnosed with cancer. Methods: Using the National Cancer Database, we identified 345,414 YAs aged 18-39 years diagnosed with cancer between 2010 and 2017. YAs diagnosed pre-expansion were followed through September 30, 2013 or three months before Medicaid expansion implementation for late-expansion states, and YAs diagnosed post-expansion were followed through December 31, 2019. We applied the difference-in-difference (DD) method to estimate changes in 2-year overall survival before and after Medicaid expansion, in expansion- versus non-expansion states, controlling for key sociodemographic factors. DD analyses were performed for YAs overall, and stratified by cancer type, stage at diagnosis, race/ethnicity, comorbidity, and facility type. Results: Among all YAs, 2-year overall survival increased more in expansion states (90.39% pre-expansion to 91.87% post-expansion) than in non-expansion states (88.98% pre-expansion to 90.05% post-expansion), resulting in a net increase of 0.53 percentage points (ppt; 95% confidence interval [CI] = 0.11 to 0.95 ppt). The increase in 2-year overall survival in expansion states versus non-expansion states was greatest among subgroups of patients with female breast cancer (DD = 1.20 ppt; 95% CI = 0.28 to 2.13 ppt) and patients with stage IV disease at diagnosis (DD = 2.51 ppt; 95% CI = 0.28 to 4.74 ppt). Additionally, greater improvement in 2-year overall survival associated with the expansion was seen among racial/ethnic minority YAs (including Hispanic, non-Hispanic Black, and non-Hispanic others; DD = 0.98 ppt; 95% CI = 0.10 to 1.86 ppt) than their non-Hispanic White peers (DD = 0.41 ppt; 95% CI = -0.06 to 0.89 ppt), among patients treated in community cancer programs (DD = 1.10 ppt; 95% CI = 0.32 to 1.88 ppt) than academic comprehensive cancer programs (DD = 0.12 ppt; 95% CI = -0.52 to 0.77 ppt), and among patients with two or more comorbidities (DD = 6.37 ppt; 95% CI = 0.68 to 12.06 ppt) than patients with no comorbidity (DD = 0.48 ppt; 95% CI = 0.04 to 0.91 ppt). Conclusions: We provide the first evidence on the association between ACA Medicaid expansion and improved overall survival among YAs newly diagnosed with cancer. Survival benefits are notable among racial/ethnic minority patients and patients with high healthcare needs, and by patients’ treatment facility type.
The initial outcome of deploying a mortality prediction tool at community oncology practices.
Authors: Ye Ping , Butler Brandon , Vo Duc , He Bo , Turnwald Brian , Hoverman John Russell , Indurlal Puneeth , Garey Jody S. , Hoang Susan Nga
Published: June 2022

1521

Background: Hospice improves the quality of life and care for cancer patients and reduces the likelihood of unwanted death in the hospital. Advance Care Planning (ACP) allows physicians to proactively initiate hospice and end-of-life discussions with identified patients, promoting timely hospice care enrollment. We developed a machine learning (ML) model to predict 90-day mortality risk for patients with metastatic cancer. The tool was designed to enable earlier ACP discussions leading to increased hospice enrollment. This study assesses the ML tool usage on ACP documentation in a community oncology setting. Methods: Twelve practices across the nation were included in the study, all participating in the Oncology Care Model. Five practices implemented the ML tool during 10/26/2020-9/30/2021, with patients scored every two weeks to provide insights on mortality risk. Patients identified as high-risk were evaluated for ACP utilization, obtained from timely EMR data and historical claims. Seven practices did not implement the ML tool and served as the control for the study. Results: A total of 1,663 patients were predicted to have a high risk of mortality at the 12 practices during the timeframe. The median age was 74 years. 53% of patients were males, and 47% were females. ACP documentation varied among the practices. The range was 19.4%-55.8% among ML tool participating practices and 7.4%-31.0% among non-participating practices. The weighted mean of ACP utilization was 34.4% for participating practices and 14.0% for non-participating practices. Compared with non-participating practices, the ACP rate increased significantly by 2.5-fold for participating practices (p-value = 0.03, two-sided T-test). Conclusions: This initial outcome study showed improved ACP documentation after deploying a mortality prediction tool in a community oncology setting. We are currently working on propensity score matching and regression analysis to reduce the effect of confounding factors such as practices, patient demographics, diagnosis, and treatment. Future studies will evaluate the impact of mortality tool use on other outcomes, including hospice enrollment, emergency department visits, and hospital admission. Implementing the mortality prediction tool is an ongoing effort with more practices planned to adopt.
The promising use of hospital at home in an oncology setting.
Authors: Kier Melanie Wain , Lubetsky Sara , Schiller Gabrielle , Siu Albert L. , Ornstein Katherine A. , Smith Cardinale B.
Published: June 2022

1523

Background: Hospitalization at Home (HaH) is an emerging clinical model that delivers the essential elements of acute hospital-level care in the home and has demonstrated efficacy largely for inpatient medical conditions. Few programs have implemented HaH for patients with active cancer diagnoses. There is little data evaluating the impact of HaH on cancer outcomes, patient experience or cost effectiveness. In 2019, the Mount Sinai Health System (MSHS) expanded its HaH program to include oncology patients. Here, we describe our institution’s experience of HaH in oncology. Methods: We performed a retrospective chart review for solid tumor, myeloma and lymphoma patients at MSHS from August 2019 to November 2021 enrolled in HaH. Patient eligibility for HaH required meeting established institutional HaH admission criteria. Demographics, cancer diagnosis, social situation, indication for antecedent ED or inpatient stay, and HaH admission were extracted from the electronic medical record. Our primary endpoint was rate of successful HaH admission, with success defined as discharge from HaH for complete recovery from the acute condition or transition to hospice. We also evaluated patient social support and home resources. Results: We enrolled 19 patients with multiple myeloma (n = 7), lymphoma (n = 1), and solid tumor (n = 11). Sixty-three percent (n = 12) were male, 74% (n = 14) were age 65 or older, and 42% (n = 8) were white. Patients were enrolled in HaH either from an inpatient service (n = 15) or from the emergency room (n = 4). While on the inpatient service, 6 of the 15 patients had received chemotherapy. Post-chemotherapy monitoring was the primary reason for HaH admission. Successful HaH admissions occurred for 79% (n = 15) of patients. The mean duration of HaH admission was 4.5 days (range 1-10 days). Three patients opted to re-enroll in HaH planned care at a later point. There were no significant issues with provider home visits, access, medication delivery, lab draws, or social support. Conclusions: The MSHS Oncology HaH program successfully cared for 79% of our cohort demonstrating the functionality of expanding the program to patients with cancer. We continue to increase enrollment for oncology patients. Further studies to assess patient outcomes, cost savings, and re-hospitalization rates when compared to the standard in hospital only care for oncology patients will help determine the benefits and preferred population to utilize oncology HaH.
Long COVID-19 in patients with cancer: Report from the National COVID Cohort Collaborative (N3C).
Authors: Sharafeldin Noha , Madhira Vithal , Song Qianqian , Bates Benjamin , Mitra Amit Kumar , Liu Feifan , Bergquist Timothy , Su Jing , Hsu Fang-Chi , Topaloglu Umit
Published: June 2022

1540

Background: Post-acute sequelae of SARS-CoV-2 or long COVID, is characterized by persistence of symptoms and/or emergence of new symptoms post COVID-19 infection. As evidence accumulates and national initiatives arise to address this increasingly prevalent syndrome, characterization of specific patient groups is still lacking including patients with cancer. Using a nationally representative sample of over 4.3M COVID-19 patients from the National COVID Cohort Collaborative (N3C), we aim to describe characteristics of patients with cancer and long COVID. Methods: We employed two approaches to identify long COVID patients within N3C: i) patients presenting to a long COVID clinic at four N3C sites and ii) patients diagnosed using the recently introduced ICD-10 code: U09.9 Post COVID-19 condition, unspecified. We included patients with at least one positive COVID-19 diagnosis between 1/1/2020 and 2/3/2022. Patients had to survive at least 90 days from the date of their COVID-19 diagnosis. Analyses were performed in the N3C Data Enclave on the Palantir platform. Results: A total of 1700 adult patients with long COVID were identified from the N3C cohort; 634 (37.3%) were cancer patients and 1066 were non-cancer controls. The most common represented cancers were skin (21.9%), breast (17.7%), prostate (8.3%), lymphoma (8.0%) and leukemia (5.7%). Median age of long-COVID cancer patients was 64 years (Interquartile Range: 54-72), 48.6% were 65 years or older, 60.4% females, 76.8% non-Hispanic White, 12.3% were Black, and 3% Hispanic. A total of 41.1% were current or former smokers, 27.7% had an adjusted Charlson Comorbidity Index score of 0, 18.6% score of 1 and 11.2% score of 2. A total of 57.2% were hospitalized for their initial COVID-19 infection, the average length of stay in the hospital was 9.6 days (SD: 16.7 days), 9.1% required invasive ventilation, and 13% had acute kidney injury during hospitalization. The most common diagnosis among the non-cancer long COVID patients was asthma (26%), diabetes (17%), chronic kidney disease (12%), heart failure (9.4%), and chronic obstructive pulmonary disease (7.8%). Among long COVID patients, compared to non-cancer controls, cancer patients were more likely to be older (OR = 2.4, 95%CI: 1.1-5.4, p = 0.03), have comorbidities (OR = 4.3, 95%CI: 2.9-6.2, p < 0.0001), and to be hospitalized for COVID-19 (OR = 1.3, 95%CI: 1.0-1.7, p = 0.05), adjusting for sex, race/ethnicity, body mass index and smoking history. Conclusions: In a nationally representative sample of long COVID patients, there was a relative overrepresentation of patients with cancer. Compared to non-cancer controls, cancer patients were older, more likely to have more comorbidities and to be hospitalized for COVID-19 warranting further investigation to identify risk factors for long COVID in patients with cancer.