bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimates of stage-specific preclinical sojourn time across 21 cancer types.
Authors: Broder Michael S. , Ailawadhi Sikander , Beltran Himisha , Blakely L. Johnetta , Budd George Thomas , Carr Laurie , Cecchini Michael , Cobb Patrick Wayne , Gibbs Sarah N. , Kansal Anuraag , Kim Ashley , Monk Bradley J. , Schwartzberg Lee S. , Wong Deborah J.L. , Yermilov Irina 
Published: June 2021

e18584 Background: Cancer progression rates following diagnosis are readily measured. However, the progression rate of cancer during the preclinical sojourn time is generally unobserved. Understanding the duration of preclinical stages (“dwell time”) would allow clinicians to better identify appropriate screening intervals for cancer. We therefore elicited estimates of progression rate during the preclinical sojourn time for a wide variety of malignancies from a panel of clinical experts. Methods: We used a validated consensus methodology (RAND/UCLA modified Delphi panel method) to elicit per-stage dwell time estimates for 20 solid cancers and lymphoma from experts. Eleven experienced oncologists (general and subspecialists) from community and academic centers reviewed literature on the natural history of disease and estimated in number of years (<1 to 9+ years) how long it would take each cancer to progress from the beginning of clinically detectable Stage I/II/III to the beginning of the next stage in untreated adults. Cancer histological subtypes were grouped and experts were asked to provide an overall rating. Ratings were completed before and after a discussion of areas of disagreement. Results: Expert estimates and range of dwell time for 21 cancer types are provided in Table. Prostate and thyroid cancer were estimated to be the slowest growing, taking approximately 7 and 5 years respectively to progress through Stage I (range 4-8), 5 years to progress through Stage II (range 3-7), and 3 and 4 (range 2-5) years respectively to progress through Stage III. Esophageal, lung, liver/intrahepatic bile-duct, gallbladder, and pancreatic cancers were estimated to progress quickly through all three stages (1-2 years per stage). Conclusions: These findings summarize practicing oncologists’ estimates of dwell time in preclinical disease. Experts agreed on dwell times although ranges were large and differences in cancer subtypes were not captured. Generally, estimates trend with published data on survival with treatment: cancers with higher survival (e.g., prostate, thyroid) were estimated to grow slower, while cancers with lower survival (e.g., pancreatic, liver/intrahepatic bile-duct, gallbladder) were estimated to grow faster. These estimates could be useful when determining screening intervals for these or any subset of these cancers. [Table: see text]
Changes in prescribing of oral capecitabine versus intravenous (IV) 5-fluorouracil (5-FU) in gastrointestinal (GI) cancers during the COVID-19 pandemic.
Authors: Civelek Yasin , Cullen Daniel , Debono David Joseph , Fisch Michael Jordan , Barron John , Sylwestrzak Gosia 
Published: June 2021

e18596 Background: Several oncology guidelines recommend using oral drugs vs. IV to minimize COVID-19 risk for patients with cancer. We examined the association between prescribing patterns of oral capecitabine vs. IV 5FU for GI cancers and social distancing, measured by the change in population mobility patterns in response to shelter-in place policies, during the pandemic. Methods: Using claims data for commercially insured members, we included patients 18 years of age or older with colorectal, gastroesophageal, or pancreatic cancer, who had continuous health plan coverage for at least 2 months before and 1 month after initiating chemotherapy with capecitabine or 5-FU from January 2017 to August 2020. We analyzed unadjusted trends in proportion of chemotherapy that was oral during pandemic (March 1st to August 31st, 2020) compared to previous years. Then, we conducted difference-in-differences analysis using COVID-19 Community Mobility Reports, by Google, and utilizing different levels of changes in mobility trends across states over time. In our main model, we used a 20% decrease in retail and recreation visits as our threshold and compared the prescribing rates in states below and above the threshold as well as before and after the pandemic began. We also used different thresholds and categories of places to check the sensitivity of our findings. Models are adjusted for age, gender, month of year, urban status, comorbidities, and state of residence at chemotherapy start date. Results: A total of 17,414 nationally distributed patients (69% colorectal, 13% gastroesophageal, 18% pancreatic) were included (mean age, 58.8 years; 41% female). During the pandemic, 1,875 patients (65% colorectal, 15% gastroesophageal, 20% pancreatic) were identified. The proportion of oral regimens did not change significantly for colorectal and gastroesophageal patients and decreased by 7.4 percentage points (pp) (p < 0.01) for pancreatic patients. In regression modelling with mobility data, oral prescribing rates for colorectal patients increased by 3.1 pp (p < 0.01), largely driven by increases for female patients (9.2 pp, p = 0.02). We observed a decrease in oral prescribing rates among pancreatic patients (-1.20 pp, p = 0.04) and did not observe a significant change for gastroesophageal patients. Our results are not sensitive to different social distancing specifications. Conclusions: We observed differential impact of the pandemic on oral prescribing rates by GI cancer type and gender. Oral prescribing increased among colorectal cancer patients driven mostly by higher oral prescribing in females. For pancreatic and gastroesophageal patients, oral prescriptions either remained unchanged or decreased. This observation may reflect a variable impact of the pandemic on women as compared to men and might involve heightened caregiving responsibilities for women.
Cancer care in the time of COVID-19: A conceptual framework to improve cancer outcomes during a pandemic.
Authors: Milch Vivienne , Anderiesz Cleola , Hector Debra , Turnbull Scott , Austen Melissa , Wang Rhona , Der Vartanian Carolyn , Keefe Dorothy Mary Kate 
Published: June 2021

e18628 Background: At the start of the COVID-19 pandemic, a plan for cancer management during a pandemic did not exist. It soon became clear that without proper planning, cancer outcomes would worsen. Cancer patients are at increased risk of COVID-19 infection, morbidity, and mortality. Health sectors internationally reduced or paused non-urgent cancer care to protect cancer patients from COVID-19. However, disproportionate delays in screening, diagnosis, and treatment can unduly impact cancer outcomes, and backlogs can further burden a strained health system. Tailored approaches to cancer management are required which balance health resource availability along with the risks of exposure and benefits of treatment. Australia’s relatively low COVID-19 case numbers afforded Cancer Australia an opportunity to proactively plan for optimal cancer management during this, and future, pandemics. Methods: Cancer Australia’s Cancer care in the time of COVID-19: A conceptual framework for the management of cancer during a pandemic (the framework) maps evidence-based cancer care considerations in relation to a health system’s capacity across acute and recovery pandemic phases, in relation to steps of the cancer care pathway. The framework promotes infection control and resource prioritisation in the context of innovative care models, triaging approaches and individualised treatment plans, underpinned by effective communication and shared decision-making. Results: The framework supports health system planning and risk-stratified approaches to guide decision-making and improve cancer outcomes. Many aspects of cancer care are recommended to continue (to varying degrees) in most pandemic phases, with modifications or pauses in some aspects of care as the pandemic curve approaches or exceeds health system capacity. Principles of the framework were employed during the second wave of COVID-19 in the Australian state of Victoria, with continuation of cancer screening programs, diagnostic investigations, and treatments wherever it was safe to do so. This resulted in reductions in cancer services and treatment being relatively smaller than in the first wave. Conclusions: Cancer management in a pandemic is not a one-size-fits-all. Countries and jurisdictions need to tailor cancer care according to the risk of the health system becoming overwhelmed. The framework guides optimal cancer care to improve outcomes for people with cancer, while minimising COVID-19 infection. As further evidence becomes available from this pandemic or in future pandemics, this framework can be refined to inform ongoing and future pandemic health system planning.
Impact of psychosocial factors on the receipt of guideline concordant care in adolescent and young adults with localized Ewing sarcoma and osteosarcoma.
Authors: Machhi Rushad , Parkes Amanda Marie 
Published: June 2021

e18658 Background: Adolescent and young adults (AYAs) experience poorer outcomes, including lower survival improvements, compared to younger and older patients. As higher compliance with National Comprehensive Cancer Network (NCCN) guidelines has been associated with improved outcomes, we sought to understand the influence of psychosocial factors on receipt of care concordant with NCCN guidelines in AYAs with bone sarcomas. Methods: Retrospective chart review was performed on adult AYA patients (18-39 years) with localized Ewing sarcoma (ES) or high-grade conventional osteosarcoma (OS) seen at least once between 2015-2019 at the University of Wisconsin (UW). These tumor types were selected given uniform guideline-based care recommendations. Chart review identified receipt of standard care as per NCCN Bone Cancer guidelines, defined as neoadjuvant chemotherapy, local therapy (surgery/radiation), and adjuvant chemotherapy with receipt of at least 75% of recommended chemotherapy cycles, and compared to interpersonal relationships (marital status and presence of children at cancer diagnosis), changes in school or work following cancer diagnosis, substance use, and residential location. Results: We identified 21 AYA patients with localized ES (10/21, 48%) or OS (11/21, 52%), with 67% (14/21) receiving NCCN guideline concordant care. Receipt of guideline concordant care was associated with interpersonal relationships, with only 33% (1/3) of patients with children versus 72% (13/18) of patients without children receiving guideline concordant care. Additionally, the one patient noted to divorce following cancer diagnosis did not receive guideline concordant care (0/1, 0%) as compared with 67% (10/15) of single patients and 80% (4/5) of married patients. Vocational changes also affected care, with only 56% (5/9) of patients with work change following cancer diagnosis receiving guideline concordant care versus 75% (9/12) without work changes. Guideline concordant care was less common in patients with alcohol use (5/10, 50%) as compared with patients without alcohol use (9/11, 82%). Residential distance to UW was also associated with receipt of guideline concordant care, which was more common in patients living 0-20 miles from UW (86%, 6/7) as compared with those 21-100 miles from UW (60%, 6/10) or > 100 miles from UW (50%, 2/4). Conclusions: Given the occurrence of cancer during a complex developmental time, AYAs have a relatively high occurrence of psychosocial changes and needs, which we found to be associated with receipt of NCCN guideline concordant care in patients with localized ES and OS. While a limited sample size, as the first study to define specific psychosocial factors that affect receipt of guideline concordant care, these finding suggest the need to improve identification and support of these discrete patient factors.
Real-world clinical adverse events (AEs) among nonmetastatic castration-resistant prostate cancer (nmCRPC) patients treated with novel anti-androgen (AA) therapies: A retrospective database study.
Authors: Freedland Stephen J. , Appukkuttan Sreevalsa , Yao Jianying , Du Yuxian , Parkin Jacqueline , Partridge Jamie , Kong Sheldon 
Published: June 2021

e18675 Background: Novel AA agents, such aspalutamide (Apa), enzalutamide (Enza) and darolutamide (Daro) are approved for the treatment of nmCRPC. In clinical trials, they were associated with AEs such as fatigue, fractures and falls. This study aimed to describe the real-world incidence of AEs among nmCRPC patients who initiated treatment with AA agents. Methods: Claims from Optum Clinformatics Data Mart, a large single-payer claims database were used to retrospectively identify adult males with prostate cancer (PC), evidence of castration, absence of metastases codes and >1 claim for AA therapies Apa and Enza (index date) from Jan 2017 through Dec 2019. Daro, a more recently approved AA, was not included due to lack of data. Incidence of central nervous system (CNS) (including but not limited to fatigue, falls and cognitive impairment) and any AE (fracture, rash, hypertension among others) were estimated and Kaplan-Meier analyses were used to quantify the median time from therapy initiation to clinical event occurrence. Multivariable Cox-proportional hazards model was used to identify clinical event predictors. A washout of previous AE events in the 1-year baseline was applied to identify true incident events. Results: A total of 605 patients (156 Apa and 449 Enza) were included in the study. The majority were ≥65 yrs (94.0%), white (56.0%), resided in the south (47.1%), and had Medicare insurance (86.4%). Almost all were medically castrated (99.0%) and mean Charlson Comorbidity Index (CCI) Score was 2.28. Incidence rates of all clinical events and CNS-related events were high (71.2% and 46.1%, respectively) with no major differences between Apa and Enza (Table). The median time from Apa or Enza treatment initiation to any clinical event was 71 and 64 days, respectively, and 282 and 209 days for CNS-related events, respectively. Significant predictors of having any events included age >75 yrs and high CCI score. Similar predictors were found for any CNS events. Conclusions: More than 70% of Apa and Enza treated nmCRPC patients had at least 1 clinical AE. Given the lack of a control cohort, further study is needed to assess whether these events are related to AAs or represent inherent risks of these events in the underlying population of largely older men with advanced PC. Future studies are warranted with all approved agents including Daro. [Table: see text]
Identifying pre-existing dementia in older adults diagnosed with cancer using a national claims database.
Authors: Schiaffino Melody K. , Moore Alison , Schumacher Jessica R. , Gilbert Paul , Nalawade Vinit , Schempp Timothy , Murphy James 
Published: June 2021

e18678 Background: Older adults over the age of 65 represent the majority of patients diagnosed with (60%), among them, 15-30% have a pre-existing Alzheimer’s disease or related dementia (ADRD) that puts them at higher risk for over and under treatment. Studying the role of pre-existing ADRD in cancer patients is vital to understanding treatment planning behavior, patterns of health care utilization, and adverse treatment outcomes. Massive administrative datasets, or “big data” represent the information rich environment that is useful for this endeavor. Methods: Our study utilized a clinically validated algorithm to assess the prevalence of pre-existing ADRD and cancer across six cancer types. We utilized the SEER-Medicare dataset for analyzing the study years 2004-2015 (N = 337 932). We extracted ICD-9 codes to identify ADRD using the Centers for Medicaid Services Chronic Conditions Warehouse (CCW) algorithm. In sensitivity analysis we compared the prevalence of ADRD+Cancer using the NCI (2014) and CCW algorithms. Results: We found a significant difference between the two algorithms (p < .0001) and a higher overall prevalence of comorbid ADRD+Cancer using the CCW (6.6%). Additionally, we found ADRD+Cancer prevalence was significantly higher among racial and ethnic subgroups compared to White and unstaged tumors compared with any numbered American Joint Committee on Cancer (AJCC) stages (p < .0001). Conclusions: Using a clinically validated algorithm we were able to identify more cases of ADRD+Cancer in big data. This figure remains underestimated for ADRD+cancer compared to clinically-validated studies. Further research into the validation approach and codes that are used for ADRD classification can improve how we identify ADRD in massive administrative data. This is critical given the growing population of diverse older adults in the U.S.
Off-label targeted therapy (TT) use in recurrent/metastatic NSCLC.
Authors: Wang Victoria , Cui Chenming , Yang Lei , Li Gerald , Schrock Alexa Betzig , Li Meijuan , Venstrom Jeffrey Michael , Tolba Khaled A. 
Published: June 2021

e18688 Background: Comprehensive genomic profiling (CGP) is an established diagnostic approach to select patients for TT. As CGP gains wide adoption, an increasing number of patients are found to harbor driver mutations for which no approved TT is available. This is often addressed through use of matched TKI and mAb approved for other mutations or anatomic sites. In this work, we examined the clinical efficacy of off-label TT in R/M NSCLC. Methods: Using a de-identified NSCLC clinico-genomic database (CGDB), we identified 6590 NSCLC patients who underwent Foundation Medicine CGP, of whom 17.8% harbored an actionable genomic alteration (GA) for which an FDA-approved TT was available and 2% (133) whose GA (MET ex-14, uncommon EGFRm, EGFR ex20ins, HER2 amp/mut, RET fusion, BRAF class 2/3) lacked an FDA-approved TT (62 in 1L and 71 in ≥2L ) who received matched off-label TT. ESMO Scale for Clinical Actionability (ESCAT) was used to grade levels of evidence. For patients who progressed on initial chemotherapy (range 2 – 9 lines, median 3), we calculated clinical efficacy using the ratio of real world PFS on targeted therapy (rw-PFS2) to rw-PFS on the last prior line of therapy (rw-PFS1) and used a cut-off of PFS2/PFS1 > 1.3 to determine off-label drug efficacy. Results: Of the 133 patients reviewed, 72 were classified as ESCAT level IB (uncommon EGFRm, MET-ex14), 45 IIB (HER2m/amp, EGFR ex-20ins), 7 IC (RET fusions). PFS varied significantly by mutation and line of therapy (table 1) with uncommon EGFRm+ and MET-ex14 exhibiting best response while EGFR ex20 ins, BRAF class 2/3 and HER2 amp fared significantly worse. 55.8% of the patients (39 of 71) reached a PFS2/PFS1 ratio > 1.3 (two-sided 95% CI, 45.3 % – 68.7 %), ranging from 93% in uncommon EGFRm+ down to 20% in HER2 amp and 44% in ex20ins. Conclusions: We provide real-world evidence to assess off-label TT in NSCLC. Clinical benefit derived from off-label TT is unevenly distributed across various mutations with most survival advantage accruing to specific mutations (MET-ex14 and uncommon EGFRm) at the expense of others (HER2 amp). Survival advantage was highly influenced by two factors: A) the timing of CGP with the earlier recipients of genomic profiling achieving better outcome, B) the identity of the driver mutation, highlighting the role of clinical actionability tier system to define level of evidence supporting such intervention.[Table: see text]
Prevalence of potential drug-drug interactions among nonmetastatic castration-resistant prostate cancer patients treated with apalutamide and enzalutamide.
Authors: Appukkuttan Sreevalsa , Fu Chunmay , Du Yuxian , Cha Ashley , Parkin Jacqueline , Gaiser Andrew , Partridge Jamie , Kong Sheldon , Freedland Stephen J. 
Published: June 2021

e18690 Background: Patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) are often treated with concurrent medications for the management of comorbid conditions. This increases the risk of drug interactions which may lead to compromised efficacy and safety of nmCRPC therapies. This study aimed to characterize potential drug-drug interactions (pDDIs) with the novel anti-androgen (AA) agents enzalutamide (Enza) and apalutamide (Apa) in a real-world nmCRPC population. Methods: We analyzed Optum Clinformatics Data Mart, a large claims database from January 1, 2017, through March 31, 2020. The study population included adult males with prostate cancer, evidence of castration, >1 pharmacy claim for Apa or Enza (index date defined as drug initiation), and without codes for metastases. Darolutamide, a more recently approved AA, was not included due to lack of data. Concomitant medications were defined as therapy with at least 1 day overlap with Apa and Enza. The top concomitant medications covering 99% of Apa and Enza population were assessed for pDDI using Micromedex, Lexicomp, and Drugs.com compendia. Results: We identified 149 Apa and 319 Enza patients with mean age 77 years across groups. The study population was primarily white (56.3% Apa; 56.7% Enza) and had Medicare insurance (81.0% Apa; 82.2% Enza). Mean Charlson comorbidity index scores were similar for each group (Apa: 2.3 [SD: 4.1]; Enza: 2.4 [SD: 2.4]). Polypharmacy was common in both groups, with the majority taking ≥5 medications (Apa: 79.8%; Enza: 75.9%). Of the co-medications included in this analysis, Micromedex, Lexicomp and Drugs.com flagged 12, 38 and 53 pDDIs for Apa, and 7, 35 and 49 pDDIs for Enza, respectively. A pDDI was identified for 35% Apa and 21% Enza patients using Micromedex and >80% of Apa and Enza patients using other compendia. The pDDIs by severity and risk rating as defined by the respective compendia are shown in Table. Specifically, 4 interactions for Apa and 1 for Enza were rated X (i.e., avoid combination). Conclusions: This study finds a high prevalence of pDDIs among Apa and Enza patients signifying the need for strict monitoring while initiating these therapies. Given the high prevalence of polypharmacy and comorbidities among nmCRPC, these patients may benefit from drugs with lower interaction potential. Future real-world analyses should be conducted to characterize the clinical and economic impact of these pDDIs as well as to assess pDDI for darolutamide. [Table: see text]