bluuebunny/crossref_metadata_2025_split huggingface dataset:
Implementing the cancer and aging research group (CARG) tool in the ambulatory oncology setting to drive informed treatment selection.
Authors: Mbewe Alexander , Pike Paula , Lewis Russell , Kortmansky Jeremy S. , Chiang Anne C. , Kanowitz Jane 
Published: September 2021

209 Background: Smilow Cancer Hospital is a NCI designated cancer center in Connecticut that has built a network of 15 community-based oncology (CBO) clinics. Older patients present with unique clinical challenges including multiple comorbidities, decreased functional status, and cognitive impairment. ASCO Geriatric Oncology guidelines recommend completing both a comprehensive geriatric assessment and a chemotherapy toxicity risk assessment on all oncology patients ≥65 years old for informed treatment selection. The CARG calculator is a simple, validated tool to assess chemotherapy toxicity risk in older patients with solid tumors. Despite ASCO guidelines, the existence of validated tools, and literature confirming improved patient outcomes, oncologists’ utilization of risk calculators is limited; therefore, we conducted a pilot CARG quality improvement initiative throughout our CBO network. Methods: 36 CBO physicians agreed to complete five CARG tools, document toxicity scores in the EMR, and complete a post-survey between March and June 2021. PDSA cycles included interventions of a hyperlink to the CARG tool incorporated in the EMR and creating a dot phrase built to simplify documentation. Education was provided on both the CARG and the survey. The survey captured perceived clinical value, time commitment, and barriers to implementation. Baseline data was collected during February 2021 and included geriatric patients receiving a new chemotherapy regimen for a solid tumor. Results: 180 consecutive new chemotherapy starts in geriatric patients were monitored. The CARG score utilization in new chemotherapy starts increased from 6.5% of new cases during the first month, to 26.4% in the third month. 82% of providers found the CARG score helpful in discussing chemotherapy risks with patients. In 32% of cases, the CARG score led to a decision to dose attenuate, and in 15% of cases, the CARG score led to a different treatment regimen. Most oncologists (65%) reported spending ≤5 minutes calculating toxicity, and 88% spent ≤10 minutes. 89% of oncologists reported the CARG score was worth the added time. Conclusions: This QI initiative demonstrates feasibility and increased use of the CARG geriatric chemotherapy toxicity tool in accordance with ASCO geriatric guideline-based care. Physician education and EMR workflow modification were utilized. In the CBO setting, oncologists found the CARG tool to be quick and helpful in discussing treatment risks with patients. Use of the CARG tool led to meaningful changes in treatment, including chemotherapy dose attenuation. Further study metrics such as palliative and supportive care referrals, ED visits, and hospitalizations will fuel sustainability.
Core elements for the implementation of primary care-based prostate cancer follow-up: A process evaluation of a randomized controlled trial.
Authors: Wollersheim Barbara M. , van Asselt Kristel M. , Akdemir Emine , Crouse Shifra , Pos Floris J. , van der Poel Henk G. , van de Poll-Franse Lonneke V , Boekhout Annelies H. 
Published: September 2021

242 Background: To improve the quality and efficiency of prostate cancer survivorship care, a randomized controlled trial (RCT) is currently comparing the safety and effectiveness of specialist- (usual care) versus primary care-based (intervention) prostate cancer follow-up. This process evaluation assessed the reach and identified constructs for the implementation of primary care-based follow-up in a RCT setting. Methods: A mixed-methods approach was used through the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework and the Consolidated Framework for Implementation Research (CFIR). We used quantitative data to evaluate the reach of the RCT and qualitative data (interviews) to indicate the perspectives of patients, general practitioners (GPs) and specialists. Thematic analysis was used to analyze the interview transcripts. Results: In total, 569 patients with localized prostate cancer from 12 hospitals were invited to participate in the trial. 18 patients were not eligible, 145 patients declined (of whom most preferred follow-up in the hospital), whereas 21 GPs declined to participate. Finally, 385 patients were randomized to specialist- (n=192) or to primary care-based (n=193) follow-up. In addition, we interviewed 15 patients, 10 GPs and 8 specialists. Participants identified several advantages of primary care- versus specialist-based follow-up: it is closer to home, more accessible, the relationship is more personal, and the hospital can focus on patients undergoing active treatment. Nevertheless, participants also identified challenges: evidence-based guidelines should be implemented, communication and collaboration between primary and secondary care should be accessible and transparent, quality indicators (i.e. PSA levels) should be collected, and GPs expect compensation (money or extra capacity). Conclusions: If the RCT shows that primary care- is equally effective as specialist-based follow-up, this study could enable the transition of prostate cancer follow-up to primary care by presenting information on the reach of an RCT and by providing advantages and challenges of primary care-based prostate cancer follow-up.
Evaluation of direct oral anticoagulant use for cancer-associated venous thromboembolism (VTE) in lung cancer.
Authors: Rostamnjad Leila , Dagogo-Jack Ibiayi 
Published: September 2021

243 Background: National Comprehensive Cancer Network recommends direct oral anticoagulants (DOACs) as preferred agents for treatment of cancer associated VTE in patients without gastric or gastroesophageal lesions. Currently at Massachusetts General hospital (MGH), DOACs are used in treatment of cancer associated VTE. This study was performed to evaluate the safety and efficacy of DOACs for treatment of VTE in patients with metastatic lung cancer. Methods: Retrospective chart review of patients at MGH with diagnosis of metastatic lung cancer who were prescribed edoxaban, rivaroxaban, or apixaban for treatment of VTE between January 2018 and January 2021 was performed. Patients were identified using electronic medical record reports. Data was collected on age, anticoagulation regimen, intent of anticoagulation therapy, presence of brain metastasis, renal function, liver function and platelet counts. The primary outcome was to assess the incidence of treatment failure, defined as VTE recurrence or major bleeding leading to a change in anticoagulation therapy. Results: 152 patients were evaluated, of which 57 received apixaban, 44 rivaroxaban, and 7 edoxaban. Most (n = 93) patients received enoxaparin for 14-90 days prior to transitioning to DOACs. Median age and creatinine clearance were 69 years and 63 mL/min, respectively. All patients had platelet count ≥ 50K/uL. Brain metastasis was present in n = 39 patients. Pulmonary embolism (PE)(n = 98), deep vein thrombosis (DVT) (n = 52), or both (n = 2) were the indication for DOAC therapy. Bleeding occurred in 14 patients including gastrointestinal bleeding (n = 5), hematuria (n = 4), epistaxis (n = 1), and hemoptysis (n = 4). Among patients with bleeding events, 7 received rivaroxaban and 7 received apixaban. Major recurrent VTE while on DOACs occurred in 5 of patients, including DVT (n = 2) and PE (n = 3). Patients with recurrent VTE received rivaroxaban (n = 7), apixaban (n = 3) and edoxaban (n = 1). All patient whom experienced bleeding and VTE were ≥ 60 years old. Brain metastasis was present in n = 2 of patients with bleeding events and n = 2 patients with recurrent VTE. Majority of patients (n = 93) received enoxaparin for 14-90 days prior to transitioning to DOACs. The median interval between initiation of DOACs and bleeding was 60 days (range 30-365) and recurrent VTE event was 90 days (range 60‐365). Conclusions: The results of this study suggest that outcomes of DOAC use for the treatment of cancer-associated VTE in patients with metastatic lung cancer are comparable to the results of large randomized controlled trials. DOAC therapy is a safe and effective anticoagulation option for lung cancer patients with cancer-associated thromboembolism.
Development of patient reported outcomes-based machine learning algorithm for the six-month mortality prediction in patients with advanced cancer.
Authors: Subbiah Ishwaria Mohan , Xu Cai , Lu Sheng-Chieh , Haider Ali , Azhar Ahsan , Swan Amy E , Amaram-Davila Jaya Sheela , Tang Michael J , Heung Yvonne , Shih Kaoswi Karina , Bruera Eduardo , Sidey-Gibbons Chris 
Published: September 2021

273 Background: To date, studies of machine learning (ML) algorithms within oncology for mortality prediction have focused on structured electronic health record (EHR) data. Given the complex symptom burden of patients with advanced cancers, ML models may be better suited to identify patterns and interactions between symptom burden and outcomes compared to traditional statistical methods. To that end, in this study, we leverage the patient reported outcomes (PRO) data together with clinical EHR-based variables to assess the performance of ML algorithms to predict mortality in patients with advanced cancers. Methods: We randomly selected 689 patients with advanced cancer who had their first Palliative Care encounter between January 2012 and December 2017. 59 patients were lost to follow-up and were excluded from this analysis. The remaining cohort of 630 patients was split 4:1 randomly into a training and validation set to develop and test a supervised ML algorithm (Extreme Gradient Boosting [XGB] tree) to predict the 6-month mortality. Candidate variables for algorithm development included gender, age, ECOG performance status (PS), number of prior systemic therapies, and scores on the Edmonton Symptom Assessment System (ESAS)-FS, a 12-item PRO measure of physical and psychosocial symptom burden include the composite Physical Symptom Score (PHS), a sum of the physical ESAS symptoms (pain, fatigue, nausea, drowsiness, shortness of breath, appetite, wellbeing, sleep). Results: Overall, 630 patients were included in this 6-month mortality prediction; mean age 59 years, 354 (56%) female; 276 (44%) male. Variables with the most significant impact on the XGB tree mortality prediction were the ESAS symptoms of shortness of breath (1-AUC, 0.295), appetite, ESAS PHS, financial distress, age, and appetite as well as ECOG PS and number of prior systemic therapies. The XGB tree algorithm demonstrated the best overall prediction performance of 6-month mortality in the independent testing set, AUC 0.716 (95% CI 0.63 - 0.81), sensitivity 0.75 (95% CI 0.66 - 0.87), and a positive predictive value 0.67 (95% CI 0.57 - 0.79). Conclusions: Our ML model leveraged PRO-based assessment of symptom burden to correctly identify the majority of patients who died within 6 months. These models are uniquely positioned to not only automatically identify patients at high risk for short-term mortality but also the specific symptoms of concern for clinical intervention. Such models can be applied to available clinical and PRO data to facilitate clinical decision-making. Futures studies on improving model performance with the inclusion of interventions to modify symptom burden are in design.
Development of a breast cancer-specific prognostic tool using CancerLinQ Discovery.
Authors: Ray Emily Miller , Zhang Xinyi , Dunham Lisette , Tan Xianming , Lafata Jennifer Elston , Reeder-Hayes Katherine Elizabeth 
Published: September 2021

275 Background: Oncologists often struggle to know which patients are near end of life to enable a timely transition to supportive care. We developed a breast cancer-specific prognostic tool, using electronic health record data from CancerLinQ Discovery (CLQD), to help identify patients at high risk of near-term death. We created multiple candidate models with varying thresholds for defining high risk that will be considered for future clinical use. Methods: We included patients with breast cancer diagnosed between 1/1/2000 to 6/1/2020 who had at least one encounter with vital signs and evidence of metastatic breast cancer (MBC). All encounters from 1/1/2000 to 7/5/2020 were included. We used multiple imputation (MI) to impute missing numeric variables and treated missing values as a new level for categorical variables. We sampled one encounter per patient and oversampled within 30 days of death, so that the event rate (death within 30 days of encounter) was about 10%. We randomly divided these patients into training (70%) and test datasets (30%). We evaluated candidate predictors of the event using logistic regression with forward variable selection. Candidate predictors included age, vital signs, laboratory values, performance status, pain score, time since chemotherapy, and ER/PR/HER2 receptor status, and change from baseline and change rate of numeric variables. We obtained a single final model by combining resulted logistic regression model from 10 MI training sets. We evaluated this final model on the MI test sets. We varied the alert threshold (i.e., high-risk proportion) from 5% to 40%. Results: We identified 9,270 patients, representing 586,801 encounters. Significant predictors of mortality were: increased age, decreased age at diagnosis, negative change in body mass index, low albumin, high ALP, high AST, high WBC, low sodium, high creatinine, worse performance status, low pulse oximetry, increased age with increased creatinine, high pain score with no opiates, increased pulse rate, unknown/missing PR, opiate use in past 3 months, and prior chemotherapy in past 1 year but not past 30 days. Candidate models had prediction accuracy of 70-89% and positive predictive value of 31-77%. Conclusions: Demographic and clinical variables can be used to predict risk of death within 30 days of a clinical encounter for patients with MBC. Next steps include selection of a preferred model for clinical use, balancing performance characteristics and acceptability, followed by implementation and evaluation of the prognostic tool in the clinic. Candidate models, varying by threshold or percentage of patients assumed to be at high risk, for the outcome of death within 30 days among patients with metastatic breast cancer.[Table: see text]
NGS testing patterns in advanced non-small cell lung cancer (aNSCLC) and metastatic breast cancer (mBC): OneOncology (OO) sites compared to Flatiron Health Nationwide (NAT).
Authors: Vanderwalde Ari M. , Ma Esprit , Yu Elaine , Szado Tania , Price Richard , Shah Anuj , Meyer Craig S. , Abbass Ibrahim M. , Grothey Axel , Staszewski Harry , Slater Dennis , Blakely L. Johnetta , Schwartzberg Lee S. 
Published: September 2021

288 Background: Personalized treatment (tx) decisions can be improved through diagnostic tests with NGS by detecting different actionable mutations. OO, a research-focused network of community practices, has a network-wide precision oncology initiative and has advocated for NGS testing in advanced cancers since 2019. This study evaluated NGS testing patterns in aNSCLC and mBC populations descriptively in OO community sites and Flatiron Health NAT. Methods: This study used the Flatiron Health EHR derived de-identified database from [1] four OO sites, and [2] NAT. Patients (pts) diagnosed (Dx) with aNSCLC (stage ≥ IIIb) or mBC from 1/1/2015 to 5/31/2020, aged ≥ 18 years, had ≥ 1 visit ≤ 90 days (d) of advanced or metastatic Dx, and had ≥ 1 biomarker test were included. NAT NGS was confirmed via abstraction from patient records. Descriptive analyses were conducted to assess NGS testing patterns and pts characteristics by tumor type. Results: Of biomarker tested pts at OO vs. NAT (community:academic: 90%:10% aNSCLC; 93%:7% mBC), 2,029 of 3,152 (64%) OO vs. 13,681 of 29,572 (46%) NAT in aNSCLC and 514 of 1,282 (40%) OO vs. 2,458 of 12,175 (20%) NAT in mBC received NGS ± other tests. Testing rate of all 5 aNSCLC biomarkers (ALK, BRAF, EGFR, ROS-1, and KRAS) was higher with NGS vs. other tests for OO (87% vs. 6%) and NAT (87% vs. 11%). In mBC, a higher testing rate of BRCA with NGS vs. other tests (OO: 68% vs. 26%, NAT: 71% vs. 28%) and similar testing rate on HER2 (OO: 98% vs. 98%, NAT: 100% vs. 99%). Median time from Dx to NGS test result at OO vs. NAT was 33 d vs. 32 d in aNSCLC and 70 d vs. 188 d in mBC. NGS testing rates increased over time, with higher rates at OO vs. NAT [Table]. Pts with NGS vs. other tests were slightly younger in aNSCLC (OO: 68 y vs. 70 y, p = 0.001; NAT: 69 y vs. 70 yr, p < 0.001) and mBC (OO: 61 y vs. 67 y, p < 0.001; NAT: 61 y vs. 66 y, p < 0.001), and slightly more commercially insured in aNSCLC (OO: 48% vs. 45%, p = 0.3; NAT: 37% vs. 33%, p < 0.001) and mBC (OO: 54% vs. 48% OO, p = 0.053; NAT: 42 % vs. 36 %, p < 0.001). Conclusions: The adoption of NGS differed by cancer type and NGS testing rates have increased over time in aNSCLC and mBC. While some pts may have received testing outside of the Flatiron network, OO had a higher NGS uptake than NAT, and had a shorter time to testing in mBC that was possibly related to a network wide strategy recommending testing at Dx of advanced disease. Future studies on tx pattern after NGS testing are warranted to improve the actionability of NGS to foster personalized tx. [Table: see text]
Trends in use of one, two, and three-line NCCNcategory 1 regimens among Medicare fee-for-service (FFS) patients receiving treatment for metastatic pancreatic cancer.
Authors: Dieguez Gabriela , Tomicki Samantha , DeStephano David , Cockrum Paul 
Published: September 2021

297 Background: There is limited research evaluating the share of patients (pts) with metastatic pancreatic cancer (m-PANC) treated according to NCCN guidelines. Methods: We identified pts with m-PANC using ICD-10 diagnosis codes in the 2016-2019 Medicare Parts A/B/D 100% Research Identifiable Files. Study pts had 2+ claims with a pancreatic cancer diagnosis and Medicare FFS coverage for 6 months pre- and 3 months post-metastatic disease diagnosis. A line of therapy (LOT) was assigned based on the order and number of therapies used. Pts with one, two, or three LOTs were defined as treated according to NCCN Category 1 guidelines if, in each LOT, pts used one of the following regimens: FOLFIRINOX (FFX), gemcitabine/nab-paclitaxel (gem/nab), gemcitabine + erlotinib, gemcitabine monotherapy, or 5-FU + leucovorin + liposomal irinotecan. Multi-drug LOTs were excluded from the analysis. Results: We identified 31,782 pts with m-PANC. 21,304 received one LOT, 7,352 received two LOTs, and 3,126 received three LOTs between 2016 and 2019. Among pts who received one or two LOTs, a higher portion were treated according to NCCN Category 1 guidelines in 2019 (72% and 43%, respectively) than in 2016 (64% and 33%, respectively). Among pts who received three LOTs, a higher portion were treated according to NCCN Category 1 guidelines in 2019 (17%) than in 2017 (12%); too few pts were treated in 2016 to make a comparison. From 2016 to 2019, FFX had the largest increase in share of pts receiving only one NCCN Category 1 LOT (11% to 27%) and gem-mono had the largest decrease (30% to 17%). Among pts receiving two NCCN Category 1 LOTs, gem/nab to liposomal irinotecan sequences had the largest increase in share of pts (18% to 32%) and gem/nab to FFX had the largest decrease (17% to 10%). Among pts receiving three NCCN Category 1 LOTs, patient share for FFX to gem/nab to Liposomal irinotecan was 35% in 2019, while gem/nab to FFX to Liposomal was 8%; pt counts in earlier years were too small to calculate patient share. Conclusions: The use of NCCN Category 1 therapies increased consistently from 2016 to 2019 among pts that received one, two, and three lines of therapy. FFX drove increases in NCCN Category 1 utilization among patients receiving one line of therapy, and gem/nab to liposomal irinotecan sequences were the primary drivers of the increase among patients receiving two lines of therapy. FFX to gem/nab to liposomal irinotecan was the primary driver of increase among patients receiving three lines of therapy.
Real-world outcomes in patients with metastatic renal cell carcinoma treated with first-line nivolumab plus ipilimumab.
Authors: Doshi Gurjyot K. , Robert Nicholas J. , Chen Liwei , Chan Philip K , Del Tejo Viviana , Stwalley Brian , Huo Stephen , Geynisman Daniel M. 
Published: September 2021

305 Background: Nivolumab plus ipilimumab (NIVO+IPI), a first-in-class combination immunotherapy, was approved by the US Food and Drug Administration in April 2018 for the treatment of intermediate- or poor-risk advanced renal cell carcinoma (RCC), and the treatment paradigm has changed dramatically over the past few years. This real-world study examined treatment patterns and sequences, treatment response, safety, and survival outcomes with this novel first-line (1L) combination therapy among patients diagnosed with metastatic RCC (mRCC) in a community oncology practice setting. Methods: A retrospective analysis of the US Oncology Network’s iKnowMed medical data examined adult patients with an International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognosis of intermediate- or poor-risk clear cell mRCC who received 1L NIVO+IPI between April 1, 2018, and March 31, 2020. Baseline demographic and clinical characteristics, treatment patterns, and treatment sequence were examined descriptively. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), duration of response (DoR), time to treatment discontinuation (TTD), and time to treatment response (TTR) were analyzed using the Kaplan–Meier method. Treatment-related adverse events (TRAEs) and healthcare resource utilization were also analyzed. Results: A total of 193 adults with stage IV mRCC treated with 1L NIVO+IPI were identified. Median age (range) was 63 (30.0–89.0) years, 73.1% were male, 69.4% were white, 56.7% were IMDC intermediate risk, and 60.6% had a documented Eastern Cooperative Oncology Group performance status of 0 or 1. Median follow-up time (range) was 9.7 (0.1–24.7) months. Median PFS (95% CI) was 17.1 (12.6–21.2) months, and the 1-year landmark PFS rate was 58.3% (50.4–65.4). At 12 months, the OS rate (95% CI) was 75.4% (67.8–81.4). The ORR (95% CI) was 43.2% (34.6–52.1) among patients with a response assessment; the median TTR (range) was 2.8 (0.3–4.1) months and median DoR was not reached. Median TTD (95% CI) was 5.8 (4.5–7.5) months. Among the 63 (31.3%) patients who received second-line therapy, 50.8% received cabozantinib and 12.7% received pazopanib. TRAEs were reported in 47.2% of patients—the most frequently reported were fatigue (13.5%), rash (10.4%), diarrhea (6.7%), nausea (6.2%), colitis (3.6%), and pruritus (3.6%). The treatment-related hospitalization rate was 5.5% and the emergency department visit rate was 3.1%. Conclusions: This real-world study supports the clinical efficacy of 1L NIVO+IPI for patients with mRCC. Our findings also suggest that the NIVO+IPI combination was generally well tolerated in the real-world setting, with low rates of adverse events and healthcare resource utilization.