bluuebunny/crossref_metadata_2025_split huggingface dataset:
Insurance coverage and care affordability in cancer survivors in 2016-2019.
Authors: Barnes Justin Michael , Adjei Boakye Eric , Schootman Mario , Graboyes Evan Michael , Osazuwa-Peters Nosayaba 
Published: June 2021

1520 Background: The Affordable Care Act (ACA) led to improvements in insurance coverage and care affordability in cancer patients. However, the uninsured rate for the general US reached its nadir in 2016 and has been increasing since. We aimed to quantify the changes in insurance coverage and rate of care unaffordability in cancer survivors from 2016 to 2019. Methods: We queried data from the Behavioral Risk Factor Surveillance System (2016-2019) for cancer survivors ages 18-64 years. Outcomes of interest were the percentage of cancer survivors reporting insurance coverage and the percentage reporting cost-driven lack of care in the previous 12 months. Survey-weighted linear probability models adjusted for covariates (age, sex, race/ethnicity, income, education, marital status, and state Medicaid expansion status) were utilized to estimate the average yearly change (AYC) in the outcomes across 2016-2019. Mediation analyses evaluated the mediating effect of insurance coverage changes on changes in cost-driven lack of care. Results: A total of 178,931 cancer survivors were identified among the survey respondents. The percentage of insured cancer survivors between 2016 and 2019 decreased from 92.4% to 90.4% (AYC: -0.54, 95% CI = -1.03 to -0.06, P =.026). This translates to an estimated 164,638 cancer survivors in the United States who lost insurance coverage in the study period. There were decreases in private insurance coverage (AYC: -1.66, 95% CI = -3.1 to -0.22, P =.024) but increases in Medicaid coverage (AYC: 1.14, 95% CI = 0.03 to 2.25, P =.043). The decreases in any coverage were largest in individuals with income < 138% federal poverty level (FPL) (AYC: -1.14, 95% CI = -2.32 to 0.04, P =.059; compared to > 250% FPL, Pinteraction=.03). Cost-driven lack of care in the preceding 12 months among cancer survivors increased from 17.9% in 2016 to 20% in 2019 (AYC: 0.67, 95% CI = 0.06 to 1.27, P =.03), which translates to an estimated 167,184 survivors in the US who skipped care due to costs. Changes in insurance coverage mediated 27.5% of the observed change in care unaffordability overall (p =.028) and 65.7% in individuals with income < 138% FPL relative to > 250% FPL (p =.045). Conclusions: Between 2016 and 2019, about 165,000 cancer survivors in the United States lost their insurance coverage and a similar number may have skipped needed care due to cost. Loss of insurance coverage was mostly among individuals with low socioeconomic status. Interventions to improve health insurance coverage among cancer survivors, such as the recent executive order to strengthen the ACA and further efforts promoting Medicaid expansion in additional states, may be important factors to mitigate these trends.
Are National Cancer Institute Cancer Centers (NCI-CC) providing adolescents and young adults (AYA) with cancer focused clinical services? A national survey.
Authors: Daunov Katherine , Daunov Michael , Noskoff Kara , Gan Hilary , Davies Simon , Larbi Olivia , Farrell Megan , Hadley Whitney , Baffa Amelia Renee , Giesel Jennifer , Egler Rachel A. , Huang Alex Yee-Chen , Letterio John J. , Lee Richard T. 
Published: June 2021

1534 Background: AYA patients with cancer have inferior outcomes compared to their pediatric and adult counterparts. The NCI recommends they be treated by AYA focused healthcare professionals within an AYA oncology program. This survey captures the current landscape of AYA oncology care in the United States. Methods: An online survey was sent to 272 cancer centers in September 2020, in coordination with Teen Cancer America and included all clinically designated NCI-CC. The survey asked about the presence of an AYA program, types of patients, dedicated resources, clinical space, type of providers, associated support services, educational efforts, importance of AYA oncology care, and how well these services are provided. Results: In total, we received 93 responses, a 34% response rate, including 50 NCI centers, a 72% response rate. Only half (49%) of NCI-CC reported having an AYA program, and 70% were started in the past 5 years. One-third (32%) of centers reported plans to start an AYA program. Most programs included patient ages from ≥15 (56%) to ≤39 (63%) with a variety of cancers – most commonly hematologic (49%) and sarcoma (49%) and least commonly lung (36%), breast (38%), and head and neck cancer (38%). AYA programs are generally embedded in both adult and pediatric oncology services (63%). On average, cancer centers reported seeing 25-50 new AYA patients/month and 100-200 follow-up visits/month. Few programs reported a dedicated inpatient space (4%) or outpatient space (9%). Most NCI-CC have supportive services available for all oncology patients, but fewer of these services were dedicated specifically to AYA patients: navigators (92% vs. 71%), social work (98% vs. 57%), psycho-oncology (96% vs. 54%), dietician (98% vs. 24%), physical therapy (98% vs. 18%), chaplaincy (98% vs. 18%), and child life (83% vs. 26%). Other services available to the AYA population included sexual health (62%), academic support (62%), and career resources (36%). A minority of centers (30%) provided AYA training to their staff. A majority of NCI-CC felt AYA programs were important-very important (60%). They reported providing good-excellent overall AYA care (59%), but this dropped to 22% for sexual health and education of staff, which was relatively consistent across centers (Table). Conclusions: This survey is the first ever national survey to assess AYA oncology programs. Despite greater emphasis on the AYA cancer population, only half of NCI-CC report having a dedicated program, and areas of improvement include education of staff and sexual health services for patients. Self-report of providing good to excellent AYA care in specific areas.[Table: see text]
Determinants of enhanced vulnerability to Covid-19 in U.K. cancer patients: Results from the OnCovid study.
Authors: Pinato David James , Scotti Lorenza , Gennari Alessandra , Colomba Emeline , Sita-Lumsden Ailsa , Loizidou Angela , Zambelli Alberto , Bower Mark , Salazar Soler Ramon , Bertuzzi Alexia Francesca , Brunet Joan , Generali Daniele Giulio , Grisanti Salvatore , Rizzo Gianpiero , Ottaviani Diego , Felip Eudald , Prat Aleix , Tabernero Josep , Diamantis Nikolaos , Cortellini Alessio ,   OncoVid study group
Published: June 2021

1574 Background: Despite high contagiousness and rapid spread, SARS-Cov-2 has led to heterogeneous outcomes across affected nations. Within Europe, the United Kingdom is the most severely affected country, with a death toll in excess of 100.000 as of February 2021. We aimed to compare the national impact of Covid-19 on the risk of death in UK cancer patients versus those in continental Europe (EU). Methods: We performed a retrospective analysis of the OnCovid study database, a European registry of cancer patients consecutively diagnosed with Covid-19 in 27 centres from February 27 to September 10, 2020. We analysed case fatality rates and risk of death at 30 days and 6 months stratified by region of origin (UK versus EU). We compared patient characteristics at baseline, oncological and Covid-19 specific therapy across cohorts and tested these in multivariable Cox regression models to identify predictors of adverse outcome in UK versus EU patients. Results: Compared to EU patients (n = 924), UK patients (n = 468) were characterised by higher case fatality rates (40.38% versus 26.5%, p < 0.0001), higher risk of death at 30 days (hazard ratio, HR 1.64 [95%CI 1.36-1.99]) and 6 months after Covid-19 diagnosis (47.64% versus 33.33%, p < 0.0001, HR 1.59 [95%CI 1.33-1.88]). UK patients were more often males, of older age and more co-morbid than EU counterparts (p < 0.01). Receipt of anti-cancer therapy was lower in UK versus EU patients (p < 0.001). Despite equal proportions of complicated Covid-19, rates of intensive care admission and use of mechanical ventilation, UK cancer patients were less likely to receive anti-Covid-19 therapies including corticosteroids, anti-virals and interleukin-6 antagonists (p < 0.0001). Multivariable analyses adjusted for imbalanced prognostic factors confirmed the UK cohort to be characterised by worse risk of death at 30 days and 6 months, independent of patient’s age, gender, tumour stage and status, number of co-morbidities, Covid-19 severity, receipt of anti-cancer and anti-Covid-19 therapy. Rates of permanent cessation of anti-cancer therapy post Covid-19 were similar in UK versus EU. Conclusions: UK cancer patients have been more severely impacted by the unfolding of the Covid-19 pandemic despite societal risk mitigation factors and rapid deferral of anti-cancer therapy. The increased frailty of UK cancer patients highlights high-risk groups that should be prioritised for anti-SARS-Cov-2 vaccination. Continued evaluation of long-term outcomes is warranted.
Can COV Direct: Effectiveness of a tele-medicine self- care interventions for cancer survivors during COVID 19 pandemic.
Authors: Warrier Narayanankutty Edavalath , Sankar Uma V , P. S. Sreedharan , Parameswaran Prasanth V. , K. V. Sajeevan , V Nirmal 
Published: June 2021

1583 Background: Good mental health improves the overall quality of life. Anxiety and depression in post-treatment cancer survivors is common and can affect adversely on the individual. CanCovDirect is a novel, tele-medicine self-care intervention for cancer survivors. We practiced a randomized controlled superiority trial to compare CanCovDirect with usual standard care (SC) in this population.Methods: Individuals completing cancer treatment within the past 3 years who had symptoms with or without anxiety or depression were recruited from clinical and community settings in Northern Kerala. We allocated the participants using block randomization (CanCovDirect plus SC or to SC alone). Assessments of anxiety and depression severity (Centre for Epidemiological Studies-Depression scale [CES-D]; primary outcome) and secondary outcomes anxiety symptoms (Hospital Anxiety and Depression Scale) health-related quality of life (Short Form Survey-12 mental and physical component summaries), were conducted at baseline, as well as 3 and 6 months (primary time point). Analyses of outcomes were adjusted for covariates using linear regression. Results: Participants recruited between June 2020 and November 2020 were randomly assigned to CanCovDirect (n = 152) or SC (n = 152). Among 350 participants randomly assigned, 304 (86.85%) completed the primary outcome at 6 months. CanCovDirect participants reported less severe anxiety and depressive symptoms on the CES-D than SC participants at 6 months, adjusted effect size (ES) 1.68 (95% CI, 1.28 to 2.05). CanCovDirect participants also had significantly greater quality of life compared with SC. Exploratory analysis suggested that types of cancer was a modifier of the primary outcome (interaction term P value =.04); the intervention was effective in women (ES, 0.62; 95% CI, −0.45 to 0.89). Conclusions: CanCovDirect is an essential method of managing mild-moderate depression and anxiety symptoms in cancer survivors.
Outcomes of first, second, and third-generation anaplastic lymphoma kinase (ALK) inhibitors in non-small cell lung cancer brain metastases (NSCLCBM).
Authors: Tatineni Vineeth , O'Shea Patrick Joseph , Rauf Yasmeen , Jia Xuefei , Murphy Erin Sennett , Chao Samuel T. , Suh John H. , Peereboom David M. , Ahluwalia Manmeet Singh 
Published: June 2021

2034 Background: Non-small cell lung cancer (NSCLC) is the most common cause of brain metastases. ALK, which codes for tyrosine kinase receptors, is rearranged in 4-7% of NSCLC. First-generation ALK inhibitors have restricted efficacy due to poor blood-brain barrier (BBB) penetration and ALK-resistant tumor mutations. Second-generation ALK inhibitors have shown better BBB penetration, while third-generation ALK inhibitors were efficacious even against ALK-resistant mutations. In this retrospective study, we investigated the overall survival (OS) and progression-free survival (PFS) in NSCLCBM patients treated with first, second, and third-generation ALK inhibitors. Methods: NSCLCBM patients between 2010 and 2019 were evaluated. We analyzed data regarding molecular marker status, systemic therapies, and date of progression. OS was defined as the start date of systemic therapy to the date of last follow-up or death. The Cox proportional model was used to estimate OS and PFS. Results: A total of 90 patients had ALK gene rearrangement. 16 ALK positive patients received first-generation ALK inhibitor (crizotinib), with a median age of 59.2 years, 50% of the cohort being female and 83.3% being white. Another 17 patients received second-generation (alectinib, ceritinib, brigatinib) and third-generation ALK inhibitors (lorlatinib), with a combined median age of 52.2 years and a cohort of 52.6% females and 72.2% white patients. The 5-year OS rate was 49% (95% confidence interval (CI) = 24%, 71%) for first-generation ALK inhibitors and 76% (95% CI = 40%, 92%) for second and third-generation ALK inhibitors (p-value (p) = 0.019). The median PFS (mPFS) for patients who received first-generation ALK inhibitors was 45.3 months and for those who received second or third-generation ALK inhibitors was 180.1 months. The respective 5-year PFS rate was 43% (95% CI = 19%, 65%) and 72% (95% CI = 42%, 89%). Conclusions: Newer generations of targeted therapies in NSCLCBM have improved BBB penetration and effectiveness against resistant mutations. We determined that there was a significant 5-year OS benefit in patients who received second and third-generation ALK inhibitors compared to first-generation ALK inhibitors, and a respective trend towards significant PFS benefit in newer-generation ALK inhibitors when compared to first-generation. These results are encouraging, but the effect on intracranial lesion size and response rates should be examined in the future.[Table: see text]
A phase I/IIa study to evaluate the safety and efficacy of blood-brain barrier (BBB) opening with the SonoCloud-9 implantable ultrasound device in recurrent glioblastoma patients receiving IV carboplatin.
Authors: Idbaih Ahmed , Ducray Francois , Stupp Roger , Baize Nathalie , Chinot Olivier L. , De Groot John Frederick , Guyotat Jacques , Sonabend Adam M. , Menei Philippe , Dufour Henry , Weinberg Jeffrey , Desseaux Carole , Canney Michael , Schmitt Charlotte , Carpentier Alexandre 
Published: June 2021

2049 Background: Low intensity pulsed ultrasound (LIPU) in conjunction with intravenous microbubbles can transiently and reversibly disrupt the blood-brain barrier (BBB), allowing for an increase in the tissue concentration of chemotherapy agents in the brain. Mass spectrometry data from preclinical models (mouse, swine) showed a > 5x enhancement in carboplatin brain concentrations, which correlated well with the spatial distribution of a Gadolinium (Gd) contrast agent used for magnetic resonance imaging (MRI). Methods: The primary objective of this phase I/IIa study (NCT03744026) was to demonstrate the safety of BBB disruption using LIPU in patients with recurrent glioblastoma. This study was a 3+3 design using escalating numbers (3, 6, 9) of activated 1 MHz ultrasound emitters. Nine patients were treated in the escalation phase and another 12 patients were treated with 9 emitters in the expansion phase. Eligibility included recurrent GBM (any recurrence) with a maximum tumor size of < 70 mm. The SonoCloud-9 device (CarThera, Paris, France) was implanted during tumor debulking/resection surgery and replaced the bone flap, with the device targeting the tumor and surrounding peritumoral brain. The device was activated every four weeks for a duration of 270 seconds, concomitantly with IV DEFINITY microbubbles (10 ml/kg), to disrupt the BBB prior to administration of carboplatin (AUC 4-6). MRI was performed to verify safety and evaluate efficacy of BBB disruption with Gd enhancement. Results: No DLTs were observed. The overall tolerance of the SonoCloud-9 implant was good, with two transient, manageable grade 3 wound infections and one grade 1 acquired meningocele event considered as probably related to the overall procedure. The most frequent neurologic adverse events were grade 1 blurred vision (5%) and dizziness (5%). Conclusions: Significant Gd enhancement was observed after more than 90% of sonication sessions, suggesting effective BBB disruption and carboplatin enhancement. Clinical trial information: NCT03744026.
The clinical significance of telomerase reverse transcriptase (TERT) promoter mutations, telomere length and O6-methylguanine DNA methyltransferase (MGMT) promoter methylation status in newly diagnosed and recurrent IDH-wildtype glioblastoma (GBM) patients (PTS): A large mono-institutional study.
Authors: Lombardi Giuseppe , Giunco Silvia , Cavallin Francesco , Angelini Chiara , Caccese Mario , Cerretti Giulia , De Bonis Pasquale , De Rossi Anita , Zagonel Vittorina 
Published: June 2021

2053 Background: the clinical significance of TERT promoter mutations, telomere length and their interactions with MGMT promoter methylation status in patients with IDH-wildtype GBM patients remain unclear. We performed a large mono-institutional study to better investigate their impact and their interaction on clinical outcomes Methods: TERT promoter mutations (C228T and C250T), relative telomere length (RTL) and MGMT methylation status were assessed in 278 newly diagnosed and in 65 recurrent IDH-wildtype GBM PTS which were treated at Veneto Institute of Oncology (Padua, Italy) from Dec 2016 to Jan 2020. We have retrospectively explored association between gene characteristics and neuroradiological response (RANO criteria), progression-free survival (PFS), overall survival (OS). Telomere length was measured by monochrome multiplex PCR and RTL values were calculated as a telomere/single-copy gene ratio Results: characteristics of newly diagnosed GBM PTS were: median age 63 ys, ECOG PS 0-1 in 71% of PTS, radical surgery in 38%, 78% received radiation therapy plus TMZ, MGMT was methylated in 53%, TERT promoter was mutated in 80% (75% C228T, 25% C250T), median RTL was 1.57 (range 0.4-11.37). Objective response rate was reported in 15% of PTS, median OS was 15ms (95% CI 13-18ms), median PFS was 8ms (95% CI 7-9ms). At multivariable analysis, TERT promoter mutations and RTL were not associated with clinical outcomes; about OS, TERT promoter mutations and RTL reported a HR of 1.05 (95% CI 0.64-1.64) and 0.99 (95% CI 0.89-1.10), respectively; MGMT methylated tumors showed significant improved PFS and OS with a HR of 0.54 (95% CI 0.40-0.71) and 0.47 (95% CI 0.34-0.64), respectively. All interactions among MGMT status, TERT mutation status and RTL were not statistically significant. Characteristics of recurrent GBM PTS were: median age 55 ys, ECOG PS 0-1 in 60% of PTS, MGMTmet in 37%, TERT promoter mutations in 75% (75% C228T, 25% C250T), RTL was 1.67 (range 0.68-8.87). At multivariable analysis, only MGMT methylated tumors resulted significantly associated to prolonged OS (HR 0.16; 95% CI 0.07-0.40). No gene interaction was significant. Conclusions: for the first time worldwide, we analyzed the impact of TERT promoter mutations, RTL and MGMT methylation status in both newly diagnosed and recurrent IDH-wildtype GBM PTS. TERT promoter status and RTL were not associated with clinical outcomes at both diagnosis and relapse. MGMT promoter methylation status was the only prognostic factor in both cases. No significant interaction was demonstrated between TERT promoter mutations, RTL and MGMT methylation status.
Phase 1 trial of drug resistant immunotherapy: A first-in-class combination of MGMT-modified γδ t cells and temozolomide chemotherapy in newly diagnosed glioblastoma.
Authors: Nabors Louis B. , Lamb Lawrence S. , Beelen Melissa Jo , Pillay Thriumaine , ter Haak Mariska , Youngblood Samantha , Vaickus Louis , Lobbous Mina 
Published: June 2021

2057 Background: Temozolomide (TMZ) transiently upregulates NKG2D ligands targeted by innate immune effector cells. Lymphodepletion impairs this immune response, however, genetic modification of ex vivo expanded γδ T cells with an MGMT-expressing lentivector confers resistance to TMZ, allowing concurrent chemotherapy and γδ T cell infusion, thereby targeting the tumor when NKG2DL are maximally expressed. This Drug Resistant Immunotherapy (DRI) is currently being evaluated in a Phase 1 first in human study (NCT04165941) and interim safety and biologic correlative analysis are detailed here for the first dosing cohort. Methods: Adults with newly diagnosed, untreated glioblastoma (GBM), adequate organ function, and a KPS≥70% will be enrolled. Subjects undergo subtotal resection and placement of a Rickham reservoir followed 3-4 weeks by apheresis from which γδ T cells are expanded, transduced with an MGMT-expressing lentivector, harvested, and cryopreserved. Standard of care induction TMZ/radiation therapy is initiated followed by 6 cycles of maintenance TMZ. Intravenous TMZ (150mg/m2) and intracranial dosing of 1 x 107 γδ T cells occur on day 1 of each maintenance cycle. Daily oral TMZ 150mg/m2 follows for Days 2-5. Dose level 1 (DL1) subjects receive 1 fixed dose of γδ T cells and DL2 receive 3 doses administered on Day 1 of each of first 3 cycles of TMZ dependent on absence of dose limiting toxicity. Primary endpoint is safety; secondary endpoints include progression free and overall survival. Immunologic and genomic correlative analyses are being conducted at specific time points from peripheral blood and cerebral spinal fluid collected from the Rickham. Results: Six subjects (4 females, 2 males) have been enrolled in DL1. All subjects were IDH1-WT with 5 subjects MGMT unmethylated and 1 methylated. Of these, 1 generated inadequate gd T cells and 2 withdrew consent prior to DRI treatment. For the 3 that received DRI, treatment-related adverse events with maximum CTCAE Grade 3 occurred in 1 subject; UTI, dehydration, and thrombocytopenia. The most common Grade 1/2 events included: fever, leukopenia, nausea, and vomiting which were attributable to TMZ or radiotherapy. Circulating T cells remained below normal range throughout maintenance phase in 2/3 subjects. NK and gd T cell numbers remained within low normal range for 3/3 and 2/3 subjects, respectively. Serum Th1 (IFNg, IL-2, TNFa) and Th2 (IL4, IL5, IL-10) cytokines were within clinical range although TNFa remained elevated from the gdT cell infusion through day +30 in 2 subjects. Conclusions: Administration of MGMT-gene modified gdT cells and TMZ as DRI is feasible in lymphodepleted subjects during TMZ maintenance phase and sufficiently safe to warrant further investigation at additional doses. Clinical trial information: NCT04165941.