bluuebunny/crossref_metadata_2025_split huggingface dataset:
Naxitamab chemo-immunotherapy regimens other than with irinotecan/temozolomide for patients with relapsed/refractory high-risk neuroblastoma.
Authors: Larrosa Cristina , Rafael Margarida Simao , Muñoz Juan Pablo , Gorostegui Maite , Castaneda Heredia Alicia , Garraus Moira , Mora Jaume 
Published: June 2024

10037 Background: Patients with relapsed/refractory (R/R) high-risk neuroblastoma (HR-NB) have dismal prognosis with chemotherapy-only salvage regimens. Naxitamab, a humanized anti-GD2 monoclonal antibody (mAb), when combined with Irinotecan and Temozolomide (I/T), has demonstrated clinically meaningful efficacy in R/R HR-NB patients (NCT03189706). We aimed to investigate the potential synergy of naxitamab with other cytotoxics. Methods: In this retrospective analysis, we examined patients treated at SJD with chemo-refractory disease, who received naxitamab in combination with chemotherapeutics other than I/T. Each cycle comprised naxitamab 2.25 mg/kg/day IV over 30 minutes, days 2, 4, 9 and 11 (total 9 mg/kg or 270 mg/m2 per cycle), and GM-CSF 250 mg/m2/day subcutaneously, days 6-10 combined with either a) cyclophosphamide (250mg/m2) and topotecan (0.75mg/m2) D1 to D5 (C/T), b) ifosfamide (1500mg/m2), etoposide (100mg/m2) D1-D3 and carboplatin (400mg/m2) D1 (ICE) or c) doxorubicin 37.5mg/m2 D1-D2 and cyclophosphamide (250mg/m2) D1-D3 (C/D). Toxicity was measured by CTCAE v4.0 and responses by INRC. Results: Twenty-nine patients received naxitamab plus GM-CSF with C/T (n=23), ICE (n=6) and C/D (n=1). One patient received both ICE and C/T. Seventeen patients had a variable number of prior relapses (1 n=14, 2 n=1, and 3 n=2). Twelve patients had refractory disease, most having received additional therapy post-induction. All but 4 patients had received naxitamab and I/T (n=20), and/or ICE (n=3/n=1), and dinutuximab-beta and I/T (n=1). Toxicities of the new regimens included myelosuppression expected with chemotherapy, and pain and hypertension expected with naxitamab. Hemorrhagic cystitis occurred in 2 patients treated with C/T, BK infection documented in one. A total of 113 cycles (median 2; 1-8) were administered, outpatient. Out of the 30 treatments, 5 achieved complete response (CR), 2 partial response (PR), and 2 mixed response (MR), providing an objective response (OR) of 30%. Eight patients achieved stable disease (SD) and 13 progressed on treatment. Disease control rate (DCR) (OR or SD) after 2 cycles was 56.6%. Patients who never responded with prior chemo-immunotherapy progressed through the new combinations. Contrary, patients who showed initial stabilization with I/T or ICE but ultimately progressed, switching drugs resulted in 60% DCR and 30% OR. Most favourable OR (75%) was seen in patients who achieved CR with prior chemoimmunotherapy and relapsed (3 out of 4). Conclusions: Naxitamab-based chemo-immunotherapy with regimens other than I/T exhibited similar and manageable toxicity profiles. Switching chemotherapeutics provided objective responses only to patients who had previously shown efficacy with I/T chemo-immunotherapy.
Burden of gastrointestinal luminal tract cancer (GLC) from 2000 to 2019 in low SDI countries.
Authors: Saowapa Sakditad , Polpichai Natchaya , Wannaphut Chalothorn , Tanariyakul Manasawee , Wattanachayakul Phuuwadith , Siladech Pharit , Olavarria Bernal Diego Alonso , Tijani Lukman Aderoju 
Published: June 2024

10558 Background: In regions with low social and economic development, gastrointestinal luminal cancer (GLC) poses a significant burden, and disparities in care are prevalent, leading to adverse disease outcomes but remain poorly studied. This study aims to assess the epidemiology of GLC in low Socio-demographic Index (SDI) regions. Methods: We analyzed temporal trends in the burden of GLC (Colorectal cancer, Esophageal cancer, Stomach cancer) using data from 2000 to 2019 from the Global Burden of Disease Study 2019. We conducted a comprehensive analysis of annual frequencies, age-standardized rates (ASRs), age-specific death rate (ASDR), and annual percentage change (APC) of luminal GI cancer incidence, death, and disability-adjusted life-years (DALYs) by sex, country, and cancer type. Results: In 2019, the frequency of incident cases due to colon cancer, esophageal cancer, and stomach cancer was 39,045, 28,132, and 43,188 respectively, with a male predominance. The number of death cases and DALYs is highest in stomach cancer, with 43,876 deaths and 1,233,251 DALYs, respectively. During 2000 to 2019, the ASDRs increased significantly for colon cancer (APC: 0.78% (0.71 to 0.84), while they decreased significantly for esophageal cancer (APC: -0.57% (-0.65 to -0.48)) and stomach cancer (APC: -1.1% (-1.26 to -0.96)). The highest ASDRs in colorectal cancer were noted in 2019 in Uganda (11.55 (9.24 - 13.75)), while the highest increase in APC in colorectal cancer was noted in Burkina Faso (APC: 1.27% (1.12 to 1.42)). Conclusions: In the preceding decade, the epidemiological landscape of GLC in low SDI countries has undergone dynamic shifts, demonstrating a heavier shift towards colorectal cancer. These findings warrant heightened awareness and strategic interventions to combat the disease.
Adverse childhood experiences and cancer: A systematic review and meta-analysis.
Authors: Mavromanoli Anna , Sikorski Claudia , Behzad Danial , Manji Karishma , Kreatsoulas Catherine 
Published: June 2024

10565 Background: Cancer is one of the leading causes of morbidity and mortality globally, with increasing incidence rates. The major governing cancer societies identify cancer risk factors into five broad groups (infectious disease, environmental/chemical pollutants, genetics, behavioral and ultraviolet radiation). However, little attention has been dedicated to understanding the potential primordial risk of the early psychosocial environment. Life course epidemiology is a framework that considers how the harmful effects of adverse childhood experiences (ACEs) contribute to the development of disease later in life. It is postulated that such stressful events that occur during a critical period of development likely trigger increased inflammatory responses, which could ultimately contribute to the manifestation of chronic diseases such as cancer. While there are studies that have reported an association between ACEs and cancer, this relationship has yet to be systematically analyzed. The objectives of this study are to a) meta-analyze the pooled association of the presence of at least one ACE, b) the burden of different ACEs, and c) specific ACE types, and their association with cancer in adulthood. Methods: This systematic review compiled studies from PubMed, EMBASE, Medline, Web of Science, Google Scholar, Biological Psychiatry, and grey literature up to Mar 16, 2023, and was registered on PROSPERO. Observational studies with a comparator group that assessed ACEs that occurred prior to age 18, and diagnosed cancer ≥21 years of age were included. Two review authors independently screened articles, extracted data, assessed risk of bias using QUIPS, and conducted GRADE assessment. Pooled odds ratios (ORs) were calculated using multilevel linear random-effects models. Results: Of the total 39,658 articles, our search identified 26 studies, of which 23 studies (356,519 participants, 9 countries) were eligible for meta-analysis. The occurrence of ≥1 ACE(s) was associated with cancer (OR=1.16, 95% CI: 1.08-1.24, I2 = 58.7%), compared to participants with no ACEs. As the number of ACEs increased, the odds of cancer increased (≥4 ACEs compared to no ACEs OR=1.30, 1.04-1.62, p-trend = 0.0003). Specific ACE types did explain a significant amount of heterogeneity (F = 2.02, p = 0.04). Parental or sibling death (OR=1.88, 1.29-2.73), household mental illness (OR=1.36, 1.14-1.61), sexual abuse (OR=1.20, 1.04-1.37), and physical abuse (OR=1.18, 1.05-1.34) had the largest associations with cancer. Conclusions: Our findings confirm ACEs as important risk factors for cancer in adulthood. These findings have important clinical and public health implications to develop primary and secondary prevention and treatment strategies. Also, further research is warranted to explore this relationship on the epigenetic level, and among specific cancers.
Early palliative care among patients diagnosed with advanced cancers in the US (2010-2019): Trends and contribution of provider variation.
Authors: Hu Xin , Kwon Youngmin , Jiang Changchuan , Fan Qinjin , Shi Sylvia Sylvia , Zheng Zhiyuan , Zhao Jingxuan , Warren Joan , Yabroff Robin , Han Xuesong 
Published: June 2024

11017 Background: Early integration of palliative care (PC) is recommended for advanced cancers, but evidence of its use and the role of provider practice patterns and organizational characteristics in uptake is limited. This study examined recent trends of early PC among Medicare beneficiaries newly diagnosed with advanced cancers, and provider- and organization-variation in the receipt of early PC. Methods: We identified patients aged ≥65.5 years newly diagnosed with advanced stage breast, colorectal, non-small cell lung (NSCL), small cell lung (SCL), pancreas, and prostate cancers in 2010-2019 with ≥6 months survival and continuous fee-for-service coverage from the linked SEER-Medicare data. Early PC was identified by claims with corresponding diagnosis codes or hospice and palliative medicine provider specialty codes within 90 days post-diagnosis or up to first hospice admission date (whichever came earlier). Treating physicians and corresponding organizations (i.e., Tax Identification Number) were assigned based on the plurality of visits within 180 days after diagnosis. We described the percent of patients receiving early PC each year. Generalized linear models with physician- and organization-fixed effects evaluated variation in early PC receipt between and within physicians/organizations. Results: Among 103,045 patients treated by 25,736 unique providers and 11,163 organizations, the percent receiving early PC increased from 0.98% in 2010 to 10.64% in 2019. Although statistically significant increases were observed across cancer types, receipt in patients with prostate cancer was relatively lower compared to pancreas, SCL, NSCL, and breast cancers (Table). After adjusting for patients’ characteristics, variation in early PC use between treating providers and organizations explained 47.9% and 31.2% of the total variation, respectively. Conclusions: Despite considerable growth in early PC receipt, utilization remained low in 2019. The large variation between providers and organizations suggests important modifiable provider behaviors and organizational characteristics in early PC use, which warrant future research. [Table: see text]
Cost-utility analysis of a supervised exercise program for patients with metastatic breast cancer in the PREFERABLE-EFFECT randomized controlled trial (RCT).
Authors: Hiensch Anouk E. , Schouten Aniek , Monninkhof Evelyn M. , Schmidt Martina , Clauss Dorothea , Trevaskis Mark , Rundqvist Helene , Wiskemann Joachim , Mueller Jana , Van Der Wall Elsken , Aaronson Neil K , Senkus-Konefka Elzbieta , Urruticoechea Ander , Bloch Wilhelm , Zopf Eva , Stuiver Martijn M. , Wengstrom Yvonne , Steindorf Karen , van der Meulen Miriam , May Anne Maria ,   on behalf of the PREFERABLE Consortium
Published: June 2024

11121 Background: Exercise for patients with metastatic breast cancer (mBC) significantly reduced fatigue and improved quality of life (QoL) in the multinational PREFERABLE-EFFECT RCT (NCT04120298). Evidence on the cost-effectiveness of exercise for patients with mBC is lacking, albeit essential for implementation in clinical practice. In this study, we evaluated the cost-utility of an exercise program for patients with mBC in the EFFECT RCT. Methods: We conducted a cost-utility analysis using data from the 357 EFFECT trial participants (mean age 55 ± 11 yrs, 75% on 1st/2nd line treatment). These participants, from centers in NL, DE, SE, PL, ES, AU, were randomized to either a 9-month supervised exercise intervention (n=178) or a usual care control group (n=179). We used a societal perspective with a time-horizon of 9 months. Two different scenario analyses (SA) were used to determine intervention costs using a bottom-up micro-costing method: SA-1) 1-on-1 supervision; SA-2) 4-on-1 supervision. Data on healthcare resource use, productivity loss and QoL (converted to QALYs) were collected with country-adapted, self-report questionnaires, including the iMCQ, iPCQ and EQ-5D-5L, at 3-, 6- and 9-months post-baseline. Multiple imputation was performed, and bootstrapping was used to study uncertainty. Results: Compared to usual care, supervised exercise led to a QALY gain of 0.015 (95% CI: -0.02; 0.05) over a 9-month period, corresponding to an increase of 5.3 days in perfect health. The mean intervention costs were €1,696 in SA-1 and €609 in SA-2. The mean total cost differences (adjusted for center and line of treatment) were -€27 (SA-1), and -€1,112 (SA-2), in favor of the exercise group ( Table). The greatest cost-savings occurred in hospital costs, meaning that the exercise group had lower hospital costs compared to the control group (€4,430 vs €5,211). The probability of supervised exercise being cost effective at a willingness-to-pay threshold of €20.000 or €80.000 per QALY gained was 62% or 76% in SA-1, and 91% or 92% in SA-2, respectively. Conclusions: Exercise for patients with mBC is likely to be cost-effective when individually supervised and even dominant (greater cost-savings and more effective) when group-based. Based on our positive findings for both effectiveness and cost-effectiveness, we recommend supervised exercise to be reimbursed as supportive care during treatment for mBC. Clinical trial information: NCT04120298 . [Table: see text]
Linking an early access program (EAP) to the National Health Data System (NHDS) in France and assessing its performances and potential biases.
Authors: Luu Vinh-Phuc , Charkaoui Icherak , Licour Muriel , Narbeburu Marion , Le Bihan Christine , Ozan Nicolas 
Published: June 2024

11137 Background: Early access programs (EAP) are a unique opportunity to document first use of innovative treatments in real-world settings. The French HTA body requires mandatory patients’ clinical data collection for EAP and since July 2021, has recommended anticipating linkage EAP to the National Health Data System (NHDS). Prior to drug initiation, the collected data is almost complete contrary to follow-up data. To the best of our knowledge, no other study has proposed a methodology to link EAP to the French Cancer cohort (FCC), an extract of the NHDS of over 8 million persons diagnosed or at high risk of cancer, and to assess its assets and downsides. Methods: This cohort study has reused data of informed French EAP patients treated with durvalumab from October 1st, 2017 to December 31st, 2018 (n=457) in locally advanced unresectable NSCLC and of patients who received durvalumab at the time of the EAP in the FCC (n=666). The linkage methodology consists in harmonizing available data across sources, defining matching, control and study variables, testing several indirect deterministic linkage algorithms and assessing their performances. Consistency and differences between data sources were described for the best performing algorithm. Results: Proposed linkage algorithms required matches on a combination of data among sex, birth year and month, treating hospital ID and department. Performance started at 80.9% (370/457) patients from the EAP cohort linked to eligible patients from FCC up to 85.3% (390/457) for the best performing algorithm. The consistency of linkage variables between the two sources was substantial (Cohen’s kappa > 0.8) or excellent (intraclass correlation > 0.9). It was the same for control variables. Comparisons between linked patients and unlinked patients from the EAP cohort showed no statistically significant difference on matching and control variables, except for few cases on history of chemotherapy and history of radiation therapy prior to durvalumab. Similarly, no statistically significant difference was found on matching and control variables between linked patients and unlinked patients from FCC, except for history of radiation therapy and treating hospital department. Median of time difference between foreseen date of first durvalumab administration in EAP versus the effective date in FCC was -1 (IQR = [-9 ; 0]) day. Lack of reported diagnosis related to prior radiation therapy administration in out-of-hospital settings refrained from using them as matching or control variables. Conclusions: The study illustrates the feasibility of matching EAP patients to the French NDHS with indirect deterministic linkage. Additional EAP linkages will be required to ensure the validation and reproducibility of such methodology. Further works in progress will document the adequacy of French NHDS data to address effectiveness.
Comparative effectiveness of the bivalent COVID-19 mRNA vaccines, mRNA1273-222 and BNT162b2, in immunocompromised adults in the US.
Authors: Kopel Hagit , Nguyen Van Hung , Bogdanov Alina , Winer Isabelle , Boileau Catherine , Ducruet Thierry , Zeng Ni , Bausch-Jurken Mary , Esposito Daina B. , Beck Ekkehard , Bonafede Mac , Mansi James A. 
Published: June 2024

e23057 Background: Despite the decline in COVID-19–related hospitalizations and mortality during the period of omicron predominance, immunocompromised individuals, including those with cancer, remain at an increased risk for severe COVID-19 outcomes. A subanalysis of a retrospective observational cohort study assessed the relative vaccine effectiveness (rVE) of 2 previously approved bivalent vaccines targeting the ancestral SARS-CoV-2 and the omicron BA.4/BA.5 variant, mRNA-1273.222 (Moderna, Inc., Cambridge, MA, USA) and BNT162b2 bivalent (Pfizer Inc., New York, NY, USA; BioNTech GmbH, Mainz, Germany), in immunocompromised adults in the United States. Methods: The study used a US electronic health record dataset (Veradigm) linked with medical and pharmacy claims data of adults aged ≥18 years with at least 1 underlying medical condition associated with increased risk of severe COVID-19 who received a dose of mRNA-1273.222 or BNT162b2 bivalent vaccines between August 31, 2022, and February 28, 2023. A subgroup analysis was conducted among an immunocompromised population, encompassing cancer patients, organ or stem cell transplant recipients, individuals with primary immunodeficiency, individuals with HIV, and individuals receiving immunosuppressing medications. Comorbid conditions were based on prior medical encounters in the 365 days before vaccination. The outcomes measured were rVE of the two bivalent mRNA vaccines against COVID-19-related hospitalizations (primary outcome) and outpatient visits (secondary outcome). Follow-up started 7 days after vaccination until May 31, 2023 (end of available claims data). Propensity score weighting was used to adjust for baseline differences between groups. Results: The subanalysis included 427,260 immunocompromised individuals, of which 250,573 (58.6%) were identified as having cancer. In the overall weighted immunocompromised population, 169,509 individuals received mRNA-1273.222, and 257,751 received BNT162b2 bivalent. The adjusted rVEs of mRNA-1273.222 versus BNT162b2 bivalent vaccine against COVID-19–related hospitalizations and outpatient visits were 15.0% (95% CI, 7.2%-22.0%; P< 0.001) and 4.8% (95% CI, 1.8%-7.7%; P= 0.002), respectively. Conclusions: In this study, the mRNA-1273.222 vaccine offered greater protection against COVID-19–related hospitalization compared with the BNT162b2 bivalent vaccine among immunocompromised individuals. This study emphasizes the importance of assessing COVID-19 vaccine formulations and optimizing protection, especially in immunocompromised adults, including those with cancer.
Assessing the missions and visions of NCI-designated cancer centers and their affiliated hospitals.
Authors: Bouvette Max Joseph , Xing Jiazhang , Moore Vanessa Ann , Lam Anh B. , Jiang Changchuan , Choradia Nirmal , Nipp Ryan David 
Published: June 2024

e23118 Background: Mission and vision statements (MVS) help convey an institution's identity and priorities. Missions describe objectives and responsibilities, while visions describe overarching directions for the future. Effectively communicating MVS is particularly important for cancer centers and hospitals seeking to inspire and reach patients and employees. We sought to assess the composition, readability, and topics addressed for MVS provided by NCI-designated cancer centers and their affiliated hospitals. Methods: We extracted MVS data from institutional websites for 65 NCI-designated cancer centers and 59 affiliated hospitals in 2023 (6 cancer centers did not have an affiliated hospital). We determined the composition of statements using word counts and time to read. We assessed the readability of statements using Flesch-Kincaid (FK) reading ease and grade level scores. We reviewed the MVS to determine the presence of four topics: equity, quality care, training, and research. We used descriptive statistics to compare these issues in MVS for cancer center versus the hospital. Results: Among the 65 cancer centers, we found mission statements for 93.9% (61/65) and vision statements for 63.1% (41/65). All affiliated hospitals provided a mission statement and 86.4% (51/59) had a vision statement. Data for composition, readability, and topics addressed for MVS are provided in the table. Overall, readability of MVS was difficult based on FK reading ease scores, with relatively high reading grade levels. Mission statements for cancer centers had a significantly lower reading ease and higher grade level compared with hospitals. In general, mission statements were slightly longer than vision statements, more frequently addressing the topics of quality care, training, and research. Compared with hospitals, cancer centers had a significantly lower frequency of mentioning the topic "training" in their MVS. Conclusions: We found that the majority of NCI-designated cancer centers report mission statements, but fewer provide vision statements. We demonstrated difficult readability for the MVS provided, highlighting a need to consider simpler diction and structure of language. Additionally, our work provides an overview of topics addressed for these statements including equity, quality care, training, and research. These topics underscore the values and priorities of an institution, and this review of MVS provides insights into the messaging that cancer centers communicate. [Table: see text]