bluuebunny/crossref_metadata_2025_split huggingface dataset:
Are we ready for biomarker driven, radiation dose–adaptable de-escalation studies for HPV+ oropharyngeal cancer?
Authors: Misiukiewicz Krzysztof , Worona Leslie , Ramos Emily J , Bakst Richard Lorne , Sindhu Kunal K. , Westra Wiliam J , Roof Scott , Posner Marshall R. 
Published: June 2023

6084 Background: Plasma circulating tumor modified viral human papillomavirus (HPV) DNA (TTMV) is a sensitive and specific biomarker of HPV+ oropharyngeal squamous cell carcinoma (HPVOPC). Patients with unresectable locally advanced (LA) HPVOPC are currently treated with induction chemotherapy (IC) and standard (sd) or reduced dose (rd) of chemoradiation (CRT). Post IC TTMV can be used in the future to help assign patients to sdCRT or rdCRT. This approach may help to maintain high efficacy and minimize long-term side effects of CRT in HPVOPC. Methods: Patients with LA HPVOPC and High Risk (HR) features (radiographic ECE, T4 primary, >N2c, and isolated lung metastases) were treated with 3 cycles of TPF IC followed by rdCRT to 5600 cGy with weekly carboplatin in responders, sdCRT in clinical non-responders and in M1 patients who also received SBRT to isolated biopsy proven lung metastases. Patients with > 20 pack year smoking history were excluded. Patients were eligible for rdCRT if they had a significant clinical response to IC and were participating in the QB2 trial (NCT02945631). Results: Fourteen subjects had pre and post IC TTMV testing available for analysis. 9/14 subjects after IC received rdCRT to 5600 cGy with weekly Carboplatin. 2 subjects were removed from the QB study for clinically inadequate response, 1 withdrew consent and 2 were M1 and treated for cure. All 5 underwent sdCRT 7000 cGy. 13/14 patients had TTMV testing done prior IC, 1 subject had TTMV done after the start of cycle 1 of IC; all 14 of them had a pretherapy or (1 subject) immediate post infusion positive elevated TTMV test. 11/14 subjects developed negative TTMV after 1 or 2 cycles IC. 3/14 subjects after 1 cycle and additional 6/14 subjects after 2 cycles of IC developed negative TTMV. 3/14 subjects still had abnormal TTMV after 3 cycles of IC; 2/3 subjects underwent 7000 cGy. Remaining 1/3 had a negative repeat TTMV prior to CRT and underwent rdCRT with 5600 cGy. TTMV testing was done for all subjects after completion CRT and all were negative. All subjects in addition to standard surveillance had TTMV testing done during their surveillance visits. 2 subjects developed recurrent HPVOPC after CRT: 1 locoregional and 1 metastatic (elevated TTMV after IC; sdCRT). Conclusions: In contrast to NCCN guidelines, rdCRT in many academic institutions has become a standard for HPVOPC. We have demonstrated a prompt reduction of TTMV to 0 in a subset of patients receiving 1 cycle and in a majority after at least 2 cycles of IC. The small sample size of our study lacks the statistical power to demonstrate that the failing to attain negative TTMV after/during IC is associated with a poor prognosis and warrants more aggressive therapy. TTMV biomarker response may have important prognostic value in delivering primary therapy and warrants further larger and more structured studies.
Tislelizumab plus chemotherapy as induction treatment followed by chemoradiotherapy or surgery in locally advanced hypopharyngeal squamous cell carcinoma: A single-arm, phase II trial.
Authors: Gui Lin , Liu Shaoyan , Wang Xiaolei , Zhang Ye , He Xiaohui 
Published: June 2023

6087 Background: Induction chemotherapy (ICT) followed by chemoradiotherapy (CRT) is the standard of care for locally advanced hypopharyngeal squamous cell carcinoma (LA HPSCC). We aimed to assess whether add immunotherapy to ICT further improving patient outcomes. Methods: In this phase II, single-arm study, eligible pts aged 18-70 yrs diagnosed with stage III-IVB (AJCC 8th) HPSCC received induction therapy with tislelizumab (200 mg), cisplatin (75 mg/m2) and nab-paclitaxel (260 mg/m2) Q3W for 3 cycles. After assessment by multidisciplinary team, pts received surgery or CRT. The primary endpoint was objective response rate (ORR). Secondary endpoints include major pathologic response (MPR) in surgery group, disease control rate (DCR), 2-yr PFS rate in CRT group and 2-yr DFS rate. Results: 29 pts were enrolled (median age, 61 y; 97% male; stage III/IVA/IVB, 7%/90%/3%) from May to Nov 2022. Median follow-up was 7.3 months, no disease progression occurred in all patients. For all pts, the post-induction ORR and DCR were 82% and 100%. In surgery group (n = 10), all pts achieved R0 resection, and 5 (50%) pts reached pathological complete response (pCR). A patient with stable disease underwent a total laryngectomy achieved pCR by postoperative pathologic evaluation. Grade 3 and 4 treatment-related adverse event (TRAE) reached 82.8%, and mainly come from chemotherapy-related neutropenia. There was no TRAE leading to treatment discontinuation. Conclusions: These early data suggested that tislelizumab plus chemotherapy as induction treatment followed by chemoradiotherapy or surgery was safe and had the potential to provide clinical benefits for patients in LA HPSCC. The inconsistency between radiographic and pathological evaluation needs further exploration. Further follow-up is needed to confirm the long-term efficacy. Clinical trial information: ChiCTR2200060094 .
A multicenter, single-arm phase 2 study of surufatinib plus toripalimab for patients with locally advanced or metastatic radioactive iodine-refractory differentiated thyroid cancer.
Authors: Ji Dongmei , Song Lijie , Cheng Ying , Shen Weina , Kuang Muyu , Chen Jiaying , Yang Minjie , Cui Hongxia , Zhou Jinghong , Shi Haiyan , Tan Panfeng , Fan Songhua , Shi Michael , Su Weiguo , Ji Qinghai 
Published: June 2023

6089 Background: For patients (pts) with radioactive iodine–refractory differentiated thyroid cancer (RAIR-DTC), there presents a considerable therapeutic challenge with poor long-term outcomes. The open-label, multi-cohort, single-arm phase 2 study was performed to evaluate surufatinib (a small-molecule inhibitor of VEGFR 1-3, FGFR1 and CSF-1R) in combination with toripalimab (an anti-PD-1 antibody) in pts with RAIR-DTC. Methods: Eligible pts were with locally advanced or metastatic RAIR-DTC who were not amenable for surgery or external beam radiotherapy, with a radiologically confirmed disease progression within 12 months before treatment, and with ≥6 months since last radioiodine treatment. Enrolled pts received surufatinib 250 mg orally, QD, plus toripalimab 240 mg IV, Q3W, until disease progression or reaching the maximum treatment duration with toripalimab of 24 months, or other protocol-specified criteria. The primary endpoint was objective response rate (ORR) per RECIST 1.1. Results: From March 2020 to November 2021, 15 pts were enrolled and received a median duration of 11.1 months of the combination treatment, with a median age of 61 years (range: 37-74). 9 (60%) pts were male, and 12 (80%) had papillary thyroid cancer. Of the 13 pts with PD-L1 immunochemical results, 6 pts had PD-L1 CPS ≥1%. As of 28 Dec 2022, the median follow-up duration was 22.11 months. Of the 15 pts with at least one post-baseline tumor assessment, the confirmed ORR was 33.3% (5 PRs) and DCR was 93.3%. mDoR was 8.34 months. mPFS (95%CI) was 10.91 months (4.01, NA). mOS was not reached, and 12-month OS rate was 100%. 14 (93.3%) pts had treatment-emergent adverse events (TEAEs), and 10 (66.7%) pts reported grade ≥3 TEAEs, most commonly (≥10% pts) with hypocalcemia (20%), diarrhea (20%) and hypertension (13%). There was no death due to TEAE in the study. Conclusions: Surufatinib plus toripalimab showed encouraging antitumor activity and tolerable safety profile in pts with locally advanced or metastatic RAIR-DTC. Clinical trial information: NCT04169672 .
Evaluation of potential socioeconomic and racial/ethnic disparities in all-cause mortality in adolescent and young adult patients with cancer.
Authors: Henderson Scott , Duggan Mark , Chao Chun , Cooper Robert Michael 
Published: June 2023

6501 Background: Adolescent Young Adult (AYA) cancer patients, aged 15-39, have historically been understudied. For older adults, socioeconomic (SES) and racial/ethnic disparities in mortality have been demonstrated, but less is known about survival disparities for AYA patients. Most existing studies do not account for the influence of insurance status and access to care. To address this gap, we evaluated the association of SES and race/ethnicity with overall mortality for AYA cancer patients who were members of an integrated health delivery system with relatively equal access to care. Methods: Patients diagnosed with cancer at age 15-39 years old in Kaiser Permanente Southern California between 2010-2018 were included. The fourteen most common AYA cancer types within our cohort were included (excluding thyroid cancer due to low mortality rate). The Neighborhood Deprivation Index (NDI) was used as a marker of SES. Patients were placed into NDI quartiles (Q1: least deprived-Q4: most deprived). Mortality rate per 1,000 patient years was calculated for each racial/ethnic group and NDI quartile. Multivariable cox model was used to estimate hazard ratios (HRs) for all-cause mortality. Models included race/ethnicity and NDI subgroup simultaneously, adjusting for sex, age and stage at diagnosis, and cancer type. Results: A total of 6,380 patients (59% female, median age: 33) were followed for a maximum of ten years. Racial/ethnic distribution was 45% Hispanic, 36% non-Hispanic White, 10% non-Hispanic Asian/Pacific Islander, 7% non-Hispanic Black, 2% Other/Unknown. Overall mortality was 21.8 deaths per 1,000 person years. Crude mortality rates were higher among Non-White racial/ethnic groups (Asian/Pacific Islander: 26.7, Black: 26.2, Hispanic: 25.6, Other/Unknown: 30.3) compared to White patients (16.4). In the adjusted model, Hispanic (HR=1.32, 95% confidence interval [CI] 1.03-1.50, p=0.004) and Black (HR=1.35, 95% CI 1.00-1.83, p=0.05) patients experienced significantly higher risk of all-cause mortality compared to White patients. No mortality differences were observed between Asian/Pacific Islander and White patients. Patients from more deprived neighborhoods had higher mortality risk (Q1: 19.9, Q2: 19.8, Q3: 24.1, Q4: 27.4). In the adjusted model, there was no significant difference in all-cause mortality between Q1 and Q2-Q4 [Q2 (HR=0.88, 95% CI 0.71-1.10), Q3 (HR=0.94, 95% CI 0.75-1.17), Q4 (HR=0.96, 95% CI 0.76-1.22)]. Conclusions: Our study suggests that for insured AYA cancer patients with similar access to care, Hispanic and Black patients have increased risk of all-cause mortality as compared to White patients, while no significant SES survival disparities were observed. These findings warrant further investigation, awareness, and intervention to address inequities in cancer care among vulnerable populations.
Disparities in outcomes among hospitalized unhoused patients with cancer in the US.
Authors: Shah Kanan , Santos Patricia Mae Garcia , Barnes Justin Michael , Tao Anna , Tsai Chiaojung Jillian , Chino Fumiko 
Published: June 2023

6502 Background: Cancer is the 2nd leading cause of death among death among unhoused adults in the US. Use of aggressive medical interventions and costs during hospitalizations remains unstudied in the unhoused population. Methods: All hospitalized adults age ≥18 with a principal cancer diagnosis were identified in the 2016-2020 National Inpatient Sample (NIS). Logistic regression tested associations between unhoused status and: cost of care, mortality, and receipt of invasive procedures/systemic therapy. Adjusted analysis accounted for patient demographics, socioeconomic status, comorbidities, and effect modification of housing status by length of stay (LOS). Results: A total of 9,030 unhoused and 2,758,693 housed adults with cancer were included in the study. There were significant ( p<0.01) differences in age <65 years (77% unhoused vs 41% housed), male sex (75% vs 53%), race (Black, 25% vs 13%; White, 58% vs 71%), and insurance type (Private, 6% vs 27%; Medicaid, 53% vs 11%). There were also differences by primary cancer diagnosis, with higher rates of lung (17% vs 14%) and liver (8% vs 3%) cancers. Unhoused persons received less chemotherapy inpatient (5% vs 7%) and fewer overall procedures (48% vs 58%), while experiencing longer LOS (median 6 vs 4 days). On adjusted analyses, unhoused adults were had lower odds of receiving invasive procedures (aOR [95%CI], 0.34 [0.27-0.42]) or systemic therapy (0.41 [0.20-0.85]); and were less likely to have a higher-than-median cost of stay 0.47 [0.39-0.57]). Additionally, unhoused adults were 35% and 20% less likely to have a higher-than-median cost of stay or die while hospitalized (95% CI 0.59 – 0.71 and 0.67 – 0.96, respectively). When accounting for the possibility of housing status being modified by LOS, unhoused persons remained significantly less likely than housed persons to receive inpatient procedures (aOR 0.38, 0.47, and 0.60 for short, medium, and long LOS, respectively; p<0.001 for each) or have high cost of stay (adjusted OR 0.55, 0.71, 0.70, p<.001 for each), though the differences by housing status were attenuated with longer length of stay. Conclusions: In this first nationwide analysis of hospitalizations among unhoused adults with cancer, unhoused patients remained significantly less likely to receive invasive procedures or systemic therapy. These disparities in inpatient management despite the higher prevalence of more aggressive cancers and comorbidities among the unhoused highlight missed opportunities to improve cancer care.
Clinical value of timely targeted therapy (TT) for patients with advanced non-small cell lung cancer (aNSCLC) with actionable driver oncogenes (ADO).
Authors: Stricker Thomas , Jain Neha , Yu Elaine , Ma Esprit , Schuldt Robert , Wang Rongrong , Sussell Jesse , Ogale Sarika , Szado Tania , Price Richard , Lin Victor T. G. , Slater Dennis , Vaena Daniel A. , Staszewski Harry , Fang Bruno , Seneviratne Lasika , Arrowsmith Edward , Daniel Davey B. 
Published: June 2023

6507 Background: Recent real-world studies observed that some aNSCLC pts with ADO initiated non-targeted therapy (non-TT) before biomarker test results became available. This study assesses the clinical impact of the timing of first line (1L) TT in aNSCLC pts with ADO. Methods: In a retrospective analysis of the nationwide Flatiron Health electronic health record-derived de-identified database, pts aged ≥18 years, diagnosed (Dx) with aNSCLC between 1/1/2015-10/18/2022, had ADO (ALK, BRAF, EGFR, RET, MET, ROS-1, or NTRK) based on biomarker testing ≤ 90 days of advanced Dx, and received 1L treatment (tx) were included. Cohorts were defined by tx patterns after test result: Cohort 1 received 1L TT ≤ 42 days; Cohort 2 initiated 1L non-TT before or after testing but switched to TT ≤ 42 days; Cohort 3 initiated non-TT before or after testing and did not switch to TT ≤ 42 days. Pts were followed from test results + 42 days until 11/30/2022 or death, whichever earliest. Multivariate Cox regression evaluated real-world progression-free survival (rwPFS) and overall survival (OS) between cohorts. Results: A total of 5156 aNSCLC pts with ADO were included: 79% were treated in the community setting and 56% received NGS testing. Most common ADO were EGFR and ALK for both Cohort 1 (78% and 13%) and Cohort 2 (67% and 24%); EGFR (39%) and BRAF (35%) for Cohort 3. Cohort 3 included more rare mutations (MET, NTRK, RET). Statistically significant differences were observed in gender, race/ethnicity, practice type, and area-level socioeconomic status across all cohorts. There was no significant difference in outcomes observed between Cohort 2 and 1, but significantly inferior outcomes in Cohort 3 vs 1. Conclusions: Our findings demonstrated better outcomes with upfront 1L TT vs non-TT in aNSCLC pts with ADO. The comparable outcomes between pts who received 1L TT after test result and pts who switched to TT ≤ 42 days of test result available underscore the importance of timely tx decisions based on ADO detection in lieu of tx-switch at progression. Opportunities remain to improve utilization of NGS to identify all ADO upfront to inform the appropriate 1L TT when indicated. [Table: see text]
Strategies to increase accrual of underrepresented populations in Alliance NCTN trials.
Authors: Paskett Electra D. , Subbiah Niveditha , Wood Marie , Steffens Craig , Kaur Judith Salmon , Adams-Campbell Lucile L. , George Suzanne 
Published: June 2023

6509 Background: Accrual of underrepresented populations (URPs-racial and ethnic minorities, women, rural populations, and younger and older populations) to clinical trials has been historically low, hampering progress in cancer treatment, symptom intervention and prevention for all. In 2018, the Alliance for Clinical Trials in Oncology (Alliance), as a part of the NCI's National Clinical Trials Network (NCTN) and a Research Base for the NCI Community Oncology Research Program (NCORP) began a multi-pronged strategy to increase accrual of underrepresented minorities by race and ethnicity (URMs) to both treatment and cancer control trials conducted by the Alliance. Methods: Alliance leadership set a goal of 20% accrual for racial and ethnic minorities to all trials in 2018. The Health Disparities Committee (HDC) implemented several strategies over time including leadership promotion/expectation of goals; funding junior investigators and special projects focusing on URPs; working groups for specific populations in HDC; HDC co-chairs to selected protocols; translation services of patient facing materials; opening studies at NCORP Minority Underserved Sites; real time monitoring of accrual demographics, by Alliance and by site; protocols addressing aims for specific populations; closing protocol enrollment to majority populations; and increasing the study sample size to enroll additional minority participants to allow for analyzing intervention effects by subgroups. Results: Accrual data from 117 NCTN and NCORP trials led by Alliance was included from 2014-2022. Over time, accrual of racial and ethnic minorities increased from 13.6% to 25.3% for treatment and 13% to 21.5% for cancer control trials. This results in overall increase from 13.5 % to 23.6% of URMs for all trials, a 74.8% improvement. Conclusions: Intentional approaches to increase URMs has led to an increase in URM accruals to Alliance trials. Future strategies include implementation of the Alliance Patient Questionnaire to prospectively measure the prevalence of specific social determinants of health among patients enrolled to further expand the understanding and address the needs of unique population accrued to Alliance trials. In addition, accrual of women, rural populations, and younger and older adults (65+ years) are now being monitored over time to increase all URP accruals.
Big data in oncology: Challenges and solutions.
Authors: Shah Neil J. , Bahadur Nadia , Niederhausern Andrew , Insinga Alysha , Shah Ibrahim , West Gianna , Ahmad Hamza , Martin Sene , Watson Adam , Nichols Chelsea , Lee Jasme , Brown Samantha , Rosenberg Jonathan E. , Moran Michael , Riely Gregory J. , Panageas Katherine , Stetson Peter D. , Bakker Theodora , Philip John 
Published: June 2023

6513 Background: Oncology care is complex and often multimodal. With recent technological advances, only a fraction of data is structured feasibly for research. Here we present a step-by-step method of building a novel comprehensive pan-cancer oncology data model using standard data definitions and industry-standard benchmarks. Methods: A team of 133 members was assembled including a project manager, bioinformatic engineers, business analysts, biostatisticians, data stewardship experts, clinical curators, and quality assurance (QA) managers. We first identified data domains that capture a comprehensive patient journey, leveraging existing oncology data models as a starting point, including NAACCR, PRISSMM (Deb Schrag & Eva Lepisto), and mCODE (ASCO). A common data model was developed using standard terms plus 5-10 disease specific elements (DSE). REDCap was used as the database platform, as it is HIPAA compliant and allows customizations. The data was stored in AuroraDB using an architecture and products that provide scalability from both an integration and consumption perspective. Results: We identified 10 data domains, including 186 distinct elements: demographics (20), comorbidities (2); cancer diagnosis & staging (27), pathology (45), imaging (18), medications (11), oncology responses (11), radiation treatments (14), cancer surgeries (11), cancer genomic (19), tumor markers (8), and vitals (8). Standard ontologies were used, including ICD-0-3 histology codes, ICD-10 comorbidities codes, CPT cancer surgeries codes, and CTCAE 5.0 for toxicities. We identified a data steward for each tumor type across medical oncology, surgery, pathology, radiology, and radiation oncology domains who aided curator training and the identification of DSE. QA managers and analysts performed 20% source data verification. In addition, we built REDCap rules (applicable across a form), and complex queries (applicable across multiple forms). To support QA and clinical engagement, interactive Tableau dashboards were constructed. In addition, timing and quality errors were monitored via Tableau dashboards at the individual curator level to provide timely feedback, leading to improved data quality and curation efficiency in real time. The Medical oncology and radiology domains were the most time-consuming, whereas Cancer diagnosis was the most difficult to curate. Conclusions: We collected genomic and phenomic data for 15,579 patients across six tumor types to date. Collecting comprehensive oncology data across tumor types is possible but requires institutional support, collaboration between clinical & informatics teams, and a dedicated QA team. [Table: see text]