bluuebunny/crossref_metadata_2025 huggingface dataset:
Current diagnostic guidelines and perpetuation of inequities in ovarian cancer: A National Cancer Database study.
Authors: Smith Anna Jo Bodurtha , Gleason Emily , Kadiyala Sneha , Wang Xingmei , Howell Elizabeth A , McCarthy Anne Marie
Published: June 2024

11027

Background: International guidelines use cancer antigen 125 (CA-125) thresholds to recommend which patients with pelvic masses should undergo evaluation by gynecologic oncologists for ovarian cancer and which patients can be observed without intervention. However, CA-125 thresholds were developed from white populations, and CA-125 levels have been shown to be 10-29% lower in healthy Black women than white women. If CA-125 levels also differ among patients with cancer, current guidelines may contribute to missed or delayed ovarian cancer diagnoses among Black women. Our objective was to examine CA-125 levels at cancer diagnosis by patient race and associations of CA-125 elevation with timely treatment. Methods: We conducted a retrospective cohort study of patients with ovarian cancer ages 0 to 90+ years diagnosed from 2018-2020 using the National Cancer Database. CA-125 was defined as positive/borderline or negative/normal by each site. We report descriptive CA-125 elevated by patient characteristics. We use multivariate logistic regression models to examine the association of patient characteristics with CA-125 level overall and for epithelial and high-grade serous cancers. We used generalized linearized models to examine the association of CA-125 with days from diagnosis to chemotherapy start for patients with Stage II-IV disease. Results: Of 38,707 patients diagnosed with ovarian cancer and with reported CA-125, 13.4% of patients did not have an elevated CA-125 at diagnosis. Patients who identified as Black, Asian, or Hispanic were less likely to have an elevated CA-125 at ovarian cancer diagnosis as were patients with early-stage disease. Among patients with high-grade serous cancer (n=18,151), 8% of Black patients had normal CA-125 at diagnosis compared to 6% of white patients. In multivariate analyses, being Black remained associated with lower odds of elevated CA-125 (OR 0.71, 95%CI 0.63-0.81), after adjustment for menopausal status, comorbidities, and stage. Even among patients with high-grade serous ovarian cancer, being black was associated with lower odds of having an elevated CA-125 (OR 0.78, 95%CI 0.64-0.96). Patients with Stage II-IV ovarian cancer who had a normal CA-125 at diagnosis had 12 days longer on average to chemotherapy initiation compared to patients with elevated CA-125. Conclusions: Current thresholds for CA-125 and gynecologic oncology referral likely miss Black patients with ovarian cancer and may delay timely treatment. Work is needed to develop inclusive CA-125 thresholds and guidelines for ovarian cancer diagnosis and not compound disparities.
Examining 1-year mortality risk among patients with malignant melanoma undergoing immune checkpoint inhibitor therapy with a history of cannabis use.
Authors: Waris Imtisaal , Raiker Rahul , Siva Nanda , Goswami Sanya , Pakhchanian Haig , Kamran Amir Shahzad
Published: June 2024

11046

Background: Cannabis use has become an increased topic of discussion in the United States due to rise in legalization, thereby increasing its accessibility for recreational and medicinal use in diseases like cancer. Immune Checkpoint Inhibitor (ICI) therapy has also recently been increasing in patient with metastatic cancers such as melanoma by targeting PD1 or PD-L1 receptors to manipulate the body’s immune response to induce cancer cell death. Cannabis is mediated in part by the CB1 and CB2 receptors in the endocannabinoid system that is present in the natural immune system. Due to the body’s immune response to cannabis, it is hypothesized this could interfere with the activity of ICI therapy. However, research examining this is sparse. Therefore, the goal was to assess mortality in malignant melanoma patients with a history of cannabis use who undergo ICI therapy. Methods: A retrospective cohort study was performed with TriNetX, a federated database of ~100 million patients across 84 healthcare organizations. Patients >17 years from 2012-2023 were identified based on ICI-therapy initiation within 1 month of malignant melanoma diagnosis. Cohorts were then created by history of those with and without cannabis use disorder. 1:1 propensity score matching was conducted to control for confounding comorbidities and demographics. Unadjusted and adjusted hazard ratios (aHR) with 95% CI were calculated for 1-year mortality after therapy initiation. HR’s were estimated using the Cox proportional hazard model. Survival curves were compared using the log-rank test. Results: A total 14589 melanoma patients who underwent ICI therapy were identified, of which 2.3% had documented cannabis use disorder. Prior to matching, melanoma patients with cannabis history had a statistically significant higher 1-year mortality compared to those with no cannabis history (HR [95%CI] = 1.29 [1.04,1.6], log rank test: p=0.0197). After matching, two balanced cohorts of 344 patients remained and adjusting for confounders revealed that melanoma patients with cannabis history had no significant difference in 1-year mortality risk compared to patients without cannabis history (1.18 [0.87,1.6], log rank test: p=0.293). Conclusions: Cannabis use among melanoma patients was shown to not have any meaningful difference in 1-year mortality risk compared to patients without cannabis use history while undergoing ICI-therapy. Additional studies, such as examining cannabis frequency and dosage, is warranted to further examine its effect.
System-level variation in evidence-based multidisciplinary cancer care delivery.
Authors: Montgomery Kelsey B. , Cotler Joseph , Richman Joshua S. , Bhatia Smita , Broman Kristy Kummerow
Published: June 2024

11064

Background: Widespread health system integration of hospitals continues to reshape the landscape of U.S. healthcare delivery. While complex cancer care has become centralized to high-volume centers, care for common cancers happens across the spectrum of hospital sizes, with known variation in receipt of evidence-based practice (EBP) based on system affiliation. Strategies are needed to evaluate system performance in order to identify system characteristics and processes that contribute to high-quality cancer care. Methods: Using a novel data linkage between the National Cancer Database and AHRQ Compendium of U.S. Health Systems, adult patients treated for breast, colon, melanoma, and thyroid cancers between 2010 and 2020 at Commission on Cancer (CoC) hospitals were identified. Systems were categorized based on number of CoC hospitals (small, 2-3; medium, 4-9; large, 10+). Eight EBP measures were developed using national multidisciplinary guidelines, and measure-specific cohorts were extracted to calculate system-level EBP performance and within-system variation using mixed effects multivariable logistic regression models. Systems were then ranked across all measures for performance and variation, and average rankings were compared by system size. Results: 3,052,453 patients with breast (60.0%), colon (17.0%), melanoma (14.0%), and thyroid (9.0%) cancers were treated at 866 CoC hospitals in 368 health systems. The 8-measure analytic cohort had 104 systems, most of which were small systems (n=74, 71.2%). Large systems (n=9, 8.7%) had worse average performance rankings compared to medium or small systems, though this was not statistically significant (p=0.1) (Table). A significant increase in within-system variation (as measured by average ranking of variability across EBP measures) was seen with increasing system size (p<0.001). Conclusions: Significant variation in EBP performance for common cancers was noted based on health system size in this large, contemporary cohort, with greater within-system variation as system size increased. Future work will identify modifiable system characteristics associated with performance that could aid system leaders and policy makers to design, measure, and incentivize systems that employ effective cancer care delivery strategies. System rankings from 1 to 104 (best to worst), averaged over all measures; data presented as median (IQR). [Table: see text]
Trends in prices of checkpoint inhibitors in the US, 2016-2023.
Authors: Paul Jeddeo , Mitchell Aaron Philip , Kesselheim Aaron S , Rome Benjamin N
Published: June 2024

11075

Background: Checkpoint inhibitors have revolutionized the treatment of several cancers since the first Food and Drug Administration (FDA) approval in 2014. Yet the cost of these drugs remains high, with implications for patient access and healthcare sustainability. We assessed pricing trends for drugs targeting program death-ligand 1 (PD-L1) or programmed cell death protein 1 (PD-1) from 2016-2023. Methods: This study included 6 PD-L1 or PD-1 inhibitors approved through 2019. Quarterly Medicare Part B spending limits, which are based on the average sales prices of drugs from manufacturers to wholesalers or direct purchasers, were collected from public files. To directly compare drugs, prices were converted to prices per month (28 days), based on the FDA-labeled dosage and frequency for metastatic non-small cell lung cancer (NSCLC), a common cancer for which each drug was approved. Prices were adjusted to 2023 dollars using the consumer price index for all urban consumers. Results: In 2016, monthly prices for pembrolizumab ($15,604) and nivolumab ($15,814) were similar. Prices for these 2 drugs and avelumab, approved in 2017, remained within 5% of each other throughout the study period. Three other drugs (cemiplimab, atezolizumab, and durvalumab) were approved from 2016-2018 and had prices 3%-20% lower than the other 3 drugs (Table). Inflation-adjusted prices for all drugs remained stable from 2016-2019 and decreased from 2020-2023, corresponding with a period of higher inflation. In 2023, monthly prices for the 6 drugs ranged from $11,961 (durvalumab) to $15,043 (pembrolizumab). From 2016-2023, inflation-adjusted prices decreased, by an average of 0.7% (pembrolizumab) to 4.8% (cemiplimab) per year. Conclusions: Although the FDA approved 6 mechanistically similar PD-1 or PD-L1 inhibitors from 2014-2018, prices remained generally unchanged during those years and through 2023, with slight declines in real prices attributable to post-COVID consumer inflation. Competition among these brand-name cancer drugs did not meaningfully affect prices. Regulators should investigate why price competition has not emerged, and policymakers should grant more opportunities to negotiate lower prices for patients and the health care system, as is being rolled out this year in Medicare following passage of the Inflation Reduction Act. [Table: see text]
Use of artificial intelligence (Al) in augmenting prior authorisation process for financial support in hemato-lymphoid malignancies: Joint project of Navya Al and Indian Cancer Society Cancer Cure Fund (ICS-CCF).
Authors: Khanna Nehal Rishi , Gokarn Anant , Sengar Manju , Rawat Ann , Thorat Usha
Published: June 2024

11086

Background: Hemato-lymphoid malignancies have a special urgency on time to initiate treatment and prior authorisation has relied on rapid review by domain experts. Since 2011, ICS-CCF has contributed over $32 million to cover the treatment costs of 14,600 underprivileged patients, including hematolymphoid malignancies. A mandate of ICS-CCF for this philanthropic funding is to choose beneficiaries who have a high chance of cure with standard of care. For this, a Due Diligence Team (DDT) of expert oncologists and the Governing Advisory Council (GAC) of ICS-CCF sequentially adjudicate every application. To augment and scale up this process, in Feb 2021, ICS-CCF evaluated and implemented the use of Al for prior-authorizations. Navya Al is a clinically validated Al model that matches clinical data of applicants with available evidence and registry data to predict survival, and generates payor/national guidelines based optimal treatment plans. Since Feb 2021, 80% of applications are adjudicated by Navya Al with a 99% concordance with GAC. Methods: This study was planned to assess the impact of Navya Al on the process of prior authorisation in a cohort of adult and pediatric hemato-lymphoid malignancies. All patients evaluated by Navya AI alone or with DDT from February 2021 to July 2023 were analyzed. Adjudication rates reflecting effort and time savings were calculated as the % of patients for whom Navya Al could make a decision on its own without referring to the DDT for review. Results: Of the 5775 applications reviewed by Navya Al, 2255(39.04%) were hematolymphoid malignancies. 37.16%(838/2255) of patients were pediatric (Age<=15years) and 62.8%(1417/2255) were adults (Age>15 years). Of these 2255, Navya AI alone adjudicated 73.61%(1660/2255) cases and 25.36%(572/2255) were referred to DDT for adjudication. Analysis was done on 2232 cases excluding the 1.01%(23/2255) reapplication cases. Details in table. Conclusions: With Al, only one fourth of beneficiary applications with hematolymphoid malignancies need expert review for prior authorisation. Implementation of AI has potential to save time in the authorization process for philanthropic funding for governmental and non governmental health care schemes. [Table: see text]
Multilevel factors associated with delays to neoadjuvant chemotherapy among young adults with operable breast cancer.
Authors: Beauchemin Melissa , Wooster Margaux , DeStephano David , Harkins Sarah , Wang Shikun , Wright Jason Dennis , Kahn Justine , Accordino Melissa Kate , Hershman Dawn L.
Published: June 2024

11091

Background: Breast cancer (BC) rates are increasing in young adults (YAs: age 18-39) and this population may experience unique barriers to treatment initiation. We identified factors associated with treatment initiation delays in a cohort of YAs with operable BC who received neoadjuvant chemotherapy (NACT). Methods: Using the National Cancer Database, we identified YAs diagnosed with non-metastatic BC from 2010-2020 who received NACT. We grouped patients by receptor status and clinical stage: 1) Hormone Receptor positive/HER-2 negative (HR+/HER2-) and were lymph node (LN) LN+; 2) HER-2 positive (HER2+) cT2+ or LN+; and 3) triple negative BC (TNBC) cT2+ or LN+. Primary outcome was delayed treatment initiation, defined as > 60 days from diagnosis date to NACT. Multivariable (MV) logistic regression was used to model factors associated with delay and adjusted for sociodemographic, clinical, and facility-level factors. We also examined factors associated with delays by tumor type. Results: Of 23,078 included patients, 62% were non-Hispanic White (NHW) and 74% had private insurance. By tumor type, 28% (n=6,350) were ER/PR+, 39% (n=8,921) were HER2+, and 34% (n=7,807) had TNBC. Most patients were treated at academic comprehensive cancer programs (ACCP) or comprehensive community cancer programs (CCCP) (40% and 34%). Treatment delays were observed among 7% of patients (n=1,638) across all tumor types. In MV analysis, non-Hispanic Black (NHB) and Hispanic YAs had 2-fold higher odds of delays compared with NHW YAs. YAs with low-income had higher odds of delays compared with higher income (OR=1.41), and YAs with private insurance had lower odds of delays compared with Medicaid (OR=0.54). YAs treated at any non-ACCP facility were less likely to experience delays. The results were similar for each tumor type. Conclusions: While the overall incidence of delays was low, significant racial, ethnic, and institutional-level treatment initiation disparities were observed among YAs receiving NACT for BC. [Table: see text]
Feasibility and utilization of electronic patient-reported outcome measures for lung cancer in routine clinical care.
Authors: Basch Ethan , Lin Huamao Mark , Cala Mary Lynn , Styliadou Melpomeni , Galaznik Aaron , Wujcik Debra , Rusli Emelly , Coombs Nicholas C , Beamon Emily R
Published: June 2024

11107

Background: Prior studies have shown the value of Patient-Reported Outcomes (PRO) in cost burden, quality of life (QoL), and survival in cancer care. To facilitate focus on patient-centricity and value-based care, the International Consortium for Health Outcomes Measurements (ICHOM) and European Health Outcomes Observatory (H2O) developed a Core Outcomes Set (COS) in lung cancer. We explored the feasibility of deploying standardized PRO measures among patients with lung cancer in US clinical practice. Methods: A retrospective database study was conducted, with IRB waiver, using Carevive PROmPT, an electronic PRO (ePRO) remote symptom monitoring platform with weekly surveys comparable in scope to ICHOM/H2O COS, of symptomatic adverse events (PRO-CTCAE), physical function (PROMIS 4A Physical Function), and QoL items (EORTC QLQ-C30 items #29,30). Severe PRO-CTCAE symptom scores triggered care team alerts. From 9/2020 to 5/2023, 207 patients enrolled across 9 US cancer centers. Patients were ≥18 years, with lung cancer, and in current treatment. Patient engagement was measured by survey compliance, follow-up time, and completeness; clinician engagement was measured by platform utilization time, time to alert response, and clinical action taken. Results: Participants were 50% female, 86% White, 12% African American, median age 68, 81% NSCLC, and 26% with metastatic disease. Median survey persistence: 8 weeks, with 85% compliance over that time. Of domains assessed, 37 (58%) from Carevive data overlapped with ICHOM/H2O COS, with 19 measured over time. Overlapping domains included 15 clinical outcomes with 60% median completion rate and 22 PRO domains with 98% median completion. Of 19 domains assessed longitudinally, median compliance was 76%. Of patients triggering ≥1 ePRO symptom alert, 87% were within 4 weeks, with 46% requesting call-backs. Median clinician follow-up to alerts was 20 hours, with 69.3% addressed within 48 hours. Clinicians accessed the platform 2-3 times weekly, for median 2 minutes (range: 1-14 minutes) per login for nurses and Advanced Practitioners (AP). 89% of alerts were addressed by nurses and AP. Of alert responses, 66% indicated continuation of treatment, 12% were escalated to the clinical team, and 1% were escalated to hospitalization or ER visit. Conclusions: Results support the feasibility of integrating a standard set of multi-domain ePRO measures, comparable to the ICHOM/H2O COS, into routine cancer care, across multiple sites, with consistent patient engagement and provider utilization. One limitation is that clinical and financial impact were not directly assessed. Future research should explore direct clinician feedback, systematic implementation of PRO measures, and impacts on patient outcomes, resource utilization, and health systems.
If you build it, they will come: Success of the EROS (Engendering Reproductive Health Within Oncologic Survivorship)—ECOG-ACRIN E1Q11 in recruitment of minority patients.
Authors: Patel Ashlesha , Lee Ju-Whei , Zaren Howard A. , Radeke Erika K , Lerner Rachel E. , Fukui Jami Aya , Makower Della F. , Tamkus Deimante , Rowland Kendrith M. , Adler William M. , Throckmorton Alyssa , ghamande sharad A. , Croley Jessica Jones , Hackney Mary Helen Helen , Pippas Andrew William , Qamar Rubina , Cella David , Fisch Michael Jordan , Wagner Lynne I.
Published: June 2024

11124

Background: The average recruitment of minority subjects in oncology trials is 4%. The ECOG-ACRIN EROS trial was designed to be inclusive of minority subjects by inviting Minority/Underserved NCI Community Oncology Research Program (MU-NCORP) sites first, with remaining sites fulfilled by inviting NCORP sites. Our objective is to examine if the EROS study recruited more than 4% minority patients, and if MU-NCORP sites provided higher rates of minority recruitment than NCORP sites. Methods: The EROS trial is a clustered randomized trial performed at 17 NCI Community Oncology Research Program (NCORP) sites (including 8 NCORP sites and 9 Minority/Underserved NCORP sites) from 2016-2023. Eligible subjects included reproductively capable women aged 15-55 with new cancer diagnosis. Intervention included RH didactics and decision aids. With respect to self-reported minority status, patients were classified into one of two categories, White and non-Hispanic/Latino or minority (non-White or Hispanic/Latino). Chi-square tests were used to evaluate distribution difference between groups and binomial tests were used for testing proportions against reference points. Results: Of the 434 patients enrolled to the trial, MU-NCORP sites recruited 266/434 (61.3%) and NCORP sites 168/434 (38.7%) patients. Among all enrolled patients, 422 patients’ race/ethnicity status could be classified. 202/422 (47.9%) self-reported as Hispanic/Latino or non-White (p<.0001 0.48 against 0.04). In MU-NCORP (174/258) 67.4% and NCORP sites (28/164) 17.1% were of minority status. (p < .0001). Conclusions: The EROS trial was designed with minority inclusion for generalizability of results. Prioritization to include MU-NCORP sites in the EROS trial did result in substantially increased minority recruitment, with the overall minority recruitment rate above usual cancer trials. Such strategy may be followed to increase minority recruitment to oncology trials.
Comprehensive molecular pathology review service to reduce barriers to precision oncology in rural eastern North Carolina.
Authors: Badami Sunil , Pun Insha , Garcia Daniela Chala , Tumin Dmitry , Zhou Yaolin
Published: June 2024

11129

Background: ECU Health system serves a rural 29-county region where cancer mortality rates exceed those of the state’s remaining 71 counties combined. Insufficient tissue and lack of local infrastructure contribute to suboptimal precision oncology care. We aimed to enhance the clinical utility of send-out molecular tests for patients with solid cancers through a quality improvement (QI) initiative. Methods: We used the EPIDEM model of QI to explore, promote, and implement a molecular review service, which includes intervening on send-out molecular orders that would otherwise have been insufficient for the requested molecular pathology test. The interventions include combining blocks, sending alternative specimens, and/or modifying testing strategy. We documented cases in a molecular send-out database and electronic health records, evaluated the service's impact, and modified it to include an orderable molecular consultation. Results: In 2023, We reviewed 699 send-out comprehensive genomic tests on solid tumors (173 cytology, 192 resections, 332 biopsies), including 582 (83.3%) advanced cancers. In total, there were 576 sufficient reports. Actions taken on 185 orders (26.5% of reviewed cases) led to 156 reported results. Of these, 70 showed clinically significant findings, and 31 patients received targeted therapy because of those interventions. In March 2023, we initiated a formal consultation service with in-depth review. From 3/3/2023-1/29/2024, we performed 50 pre-test (e.g., specimen to use, testing strategy, tumor origin testing) and 60 post-test (e.g., result interpretation, treatment based on molecular data) consultations; 10 patients received both pre and post-test support. The molecular pathologist tended to initiate post-test, while clinicians preferentially initiated pre-test consultations (p<.01). Clinician-initiated consultations were more frequent in community practices (p <.01). Conclusions: Even without the resources for in-house testing, our molecular review service provides essential pre- and post-analytic support by successfully rescuing cases that would have otherwise been insufficient molecular tests and by providing comprehensive consultative support. The positive impact and reception among community oncologists suggest that our strategy holds potential to alleviate barriers to precision oncology in underserved areas. [Table: see text]
Demographics and survival outcomes of stage IV male breast cancer: A retrospective analysis of SEER database.
Authors: Thalambedu Nishanth , Fugere Bradley , Malapati Sindhu
Published: June 2024

11142

Background: Male Breast Cancer (MBC) is a rare malignancy accounting for <1% of all breast cancer cases in the United States. It is often lately diagnosed due to lack of awareness leading to substantial morbidity and mortality. Previous studies revealed higher risk of death among males compared to females across all stages, but little known about the impact of Hormone Receptor (HR) and Human Epidermal growth factor Receptor 2(HER 2) statuses on prognosis and survival among MBC patients. So, we aim to study the survival outcomes of stage IV MBC patients using SEER (Surveillance, Epidemiology, and End Results) data. Methods: A retrospective analysis was conducted using a SEER database and identified stage IV MBC cases (Any T, Any N, M1) diagnosed between 2010-2015. The selection of these years is based on the reporting of HER2 status on SEER database starting from 2010 and to ensure a current period and a minimum of 5 years of follow-up. Patient demographics, tumor HR/HER 2 status and survival data were extracted and analyzed. Subgroup analyses were performed to show the correlation between HR/HER 2 status and survival. Results: The study included 144 patients. 59.7%(86/144) were above 60 years of age. Majority were Caucasians up to 68.1%(98/144) followed by African Americans 18.7% (27/144), Hispanics 6.9%(10/144) and Asians/Pacific Islanders 6.2%(9/144). Among the subtypes, the most common was HR+/HER2- consisting of 69.4%(100/144) followed by HR+/HER2+ 19.4%(28/144), HR-/HER2- 9.7%(14/144), HR-/HER2+ 1.4%(2/144). The median overall survival varied among different subtypes of breast cancer and was noted to be 31.5 months, 25 months, 4.5 months and 10 months among HR+/HER2-, HR+/HER2+, HR-/HER2- and HR-/HER2+ respectively (Table). In the comparison between HR+/HER2+ and HR-/HER2-, the risk of death differed significantly, as indicated by a hazard ratio of 0.26 (95% CI 0.12-0.56, p = 0.001), highlighting a poor survival of HR-/HER2-. Conclusions: This retrospective analysis provides valuable insights into the demographics and survival outcomes of stage IV MBC patients. Triple negative (HR-/HER2-) subtype continues to have poor outcomes in males as well, emphasizing the need to explore novel treatment strategies to improve outcomes for this unique patient population. Although, treatment regimens for MBC are extrapolated from women, the disparity in survival across all subtypes requires the need to get more men on breast cancer clinical trials when feasible. [Table: see text]
Retrospective analysis: Does 5-FU dose adjustment per DPYD mutation status affect toxicity?
Authors: Parekh Deevyashali , Noronha Vanita , Patil Vijay Maruti , Menon Nandini Sharrel , Shah Minit Jalan , Chougule Anuradha , Prabhash Kumar
Published: June 2024

11172

Background: 5-Fluorouracil (5-FU) forms a cornerstone in neoadjuvant chemotherapy (NACT) regimens for solid tumors including head and neck cancers. The DPYD gene encodes for enzyme dihydropyrimidine dehydrogenase (DPD) which catalyses an essential, rate-limiting step in the metabolism of 5-FU. Heterozygous genomic alteration of DPYD (30-35% of population) result in reduced potency of DPD enzyme, while homozygous DPYD alteration (0.1-0.2% of population) results in no functional DPD. Reduced functioning of DPD leads to slower metabolism of 5-FU causing toxicity such as bone marrow suppression, cytopenias etc. The Clinical Pharmacogenetics Implementation Consortium (CPIC) have released guidelines recommending reducing the dose of 5-FU in patients with these genomic alterations of DPYD from 25% to avoiding its use based on a calculated activity score (DPYD-AS). Methods: A phase III randomized study compared a DC vs DCF regimen as NACT in technically unresectable oral cancer was published in March 2024. We utilised data from the ‘DCF’ arm of this study. Patients underwent DPYD testing and we stratified these patients based on DPYD status. In the study, patients underwent the appropriate dose reductions per the CPIC guidelines based on DPYD-AS scores. We evaluate the frequency and degree of adverse events in these groups to determine whether this dose reduction effectively reduces toxicity from 5-FU in these patients. Adverse events were graded per CTCAE. Analysis by Fishers exact test. Results: 247 patients in the DCF arm were included. 85 (34.4%) did not undergo DPYD testing. 118 (47.8%) did not have any DPYD mutation, 44 (17.8%) had heterozygous mutation while 0 had homozygous mutation. The adverse events by DPYD genotypic subgroup are shown in the table. Conclusions: There was no statistically significant difference in adverse events between the group with no DPYD mutation who received the full dose of 5-FU and the heterozygous DPYD mutation group receiving a lower 5-FU dose based on DPYD-AS score. Thus, the dose reduction as set out by the CPIC appears to appropriate. [Table: see text]
A deep learning–enabled workflow to estimate real world progression-free survival in patients with metastatic breast cancer.
Authors: Varma Gowtham , Yenukoti Rohit Kumar , Kumar-M Praveen , Ashrit Bandlamudi Sai , Purushotham K , C Subash , Kumar Ravi Sunil , Kurien Verghese , Aman Avinash , Manoharan Mithun , Jaiswal Shashank , Anand Akash , Barve Rakesh , Thiagarajan Viswanathan , Lenehan Patrick , Soefje Scott A. , Soundararajan Venky
Published: June 2024

11176

Background: Progression-free survival (PFS) is frequently measured in oncology clinical trials. In analyses outside of the trial setting, various strategies have been utilized to assess real-world PFS (rwPFS), including manual abstraction of clinical records, natural language processing (NLP) of oncology notes and radiology reports, and longitudinal analyses of radiologic images. Here we develop and validate a new semi-automated workflow that combines NLP of clinical notes with structured electronic health record data to facilitate the evaluation of rwPFS in patients with metastatic breast cancer (mBC). Methods: This study analyzes de-identified EHR data using nference nSights. The data is extracted following privacy-preserving protocols and is HIPAA compliant. The overall cohort included 316 patients with HR-positive, HER2-negative mBC who initiated Palbociclib and Letrozole combination therapy between January 1, 2015 and December 31, 2021. We developed and implemented an ensemble of deep-learning NLP frameworks to capture progression events from unstructured clinical notes and radiology reports. A change in the line of therapy, as determined by structured drug order/administration records, was also considered a progression event. We used manually curated “ground-truth” datasets to evaluate the performance of the progression-event capture workflow at the levels of both sentences (N = 1000) and patients (N = 100) by calculating sensitivity, specificity, precision, accuracy, and F1 scores. Progression events and censoring events (death, loss to follow-up, end of study period) were considered to compute rwPFS. Results: At the sentence level, progression events were captured from clinical notes and radiology reports with a sensitivity of 99.8%, specificity of 96.7%, and accuracy of 98.2% (Table). At the patient level, initial progression was correctly captured within a window of +/-30 days with a sensitivity of 92.5%, specificity of 83.0%, and accuracy of 88.0% (Table). In a sample of 100 patients, the median rwPFS was determined to be 25 months (95% CI; 15-35 months) by manual curation and 22 months (95% CI; 15-35 months) by the semi-automated workflow. In the overall cohort, median rwPFS was 20 months (95% CI; 18-25 months). Conclusions: An ensemble of NLP algorithms extracted progression events from clinical notes and radiology reports with high accuracy. A semi-automated workflow enabled rapid and accurate determination of rwPFS in mBC patients receiving a combination chemotherapy regimen. Further evaluation of this workflow to estimate rwPFS in other cancers and therapeutic settings is warranted. [Table: see text]
Assessing secular trends in lung cancer stage in the United States community oncology setting from 2013 to 2023.
Authors: Herms Lisa , Su Zhaohui , Robert Nicholas J , O'Sullivan Amy K. , Paulus Jessica K
Published: June 2024

11178

Background: Detecting disease at an early stage is critical to improving lung cancer (LC) survival, as reflected in guidelines recommending screening with low dose computed tomography for individuals at high risk by clinical societies including the NCCN (2011) and US Preventive Services Task Force (2013, updated 2021). Presenting stage distribution may also be impacted by healthcare utilization changes following the COVID-19 pandemic. Real-world data (RWD)-based investigations are important complements to national cancer registries to provide insight into this potentially changing diagnostic landscape, especially given utilization, practice and referral patterns unique to community settings. We thus assessed LC stage from 2013-23 in a large, nationally representative sample of community oncology practices leveraging RWD. Methods: This is a retrospective observational cohort study of patients within The US Oncology Network and non-Network practices, which include a nationally representative network of over 3,700 providers and more than 1 million patients seen annually in community-based oncology practices. All adult (≥18 years) patients diagnosed with non-small cell LC (NSCLC) or small-cell LC (SCLC) who had a first observed stage available in the community oncology setting within 2013 to 2023 were included. Demographics and medical history data were sourced from structured data fields in iKnowMed, an oncology-specific electronic health record system. Time trends of patient diagnosis and characteristics were descriptively evaluated. Results: The analysis included 98,806 patients with LC (84,023 [85.0%] NSCLC and 14,783 [15.0%] SCLC). Approximately half were female (49.7% and 50.3% in each disease), three-fourths were White (72.7% and 77.0%, respectively), and mean ages at diagnosis were 69.9 and 68.1 years. From 2013 to 2023, there was an increase in the total number of patients observed in the database with a documented stage, from 7,159 to 9,115 (27.3% increase) for NSCLC and from 1,162 to 1,595 (37.3% increase) for SCLC. This was largely driven by an absolute increase in advanced stage diagnoses. The proportion of patients diagnosed with Stage IV NSCLC increased from 43.3% in 2013 to 49.3% in 2023, while the proportions of Stage 0/I and II diagnoses decreased. A similar trend was observed for SCLC, with 60.3% of patients diagnosed with Stage IV in 2013 compared to 68.2% in 2023. The proportion of Stage IV NSCLC cancers increased in the pandemic period, from 48.0% in 2019 to 51.6% in 2020 and 50.6% in 2021. Conclusions: Over the last decade, the proportion of advanced stage LC cases has increased, possibly reflecting changes in referral patterns and utilization specific to the community setting, including those related to the COVID-19 pandemic. The burden of advanced disease highlights the need for continuous investment in advanced-stage treatments as well as early detection efforts.
Delayed immune-related adverse events in patients with advanced melanoma treated with immune checkpoint inhibitors.
Authors: Angeles Arkhjamil , Sonke Eric , Nguyen Thao Phuong , Bahl Gaurav , Poon Vincent Isaac , Bernstein Vanessa , Weppler Alison Margaret , Savage Kerry J.
Published: June 2024

12047

Background: Immune checkpoint inhibitors (ICIs) have changed the treatment landscape of melanoma but can have serious or life-altering immune-related adverse events (irAEs). Most toxicities associated with ICIs occur within the first few months (mo) of treatment initiation, but delayed irAEs occurring 12 mo after ICI start are not well characterized. Further, clinical trials often have limited follow-up of AEs and thus, real world data is valuable. Methods: Patients (pts) ≥18 years with advanced melanoma who received ≥1 cycle of an ICI at BC Cancer from 2012-2019 with ≥12 mo of follow-up from time of ICI initiation were identified using the BC Cancer Registry and Pharmacy databases. Data on baseline clinicopathologic factors prior to the first cycle of ICI, and delayed irAE history and management were extracted. Delayed irAEs were graded using CTCAEv5. Results: In total, 530 pts treated with ≥1 cycle of an ICI were identified of which 309 pts had ≥12 mo of follow-up. Median follow-up for alive pts was 65.3 mo (13.0-143.5 mo). 96 (31%), 147 (48%), 19 (6%), and 47 (15%) pts received combination ICI (nivolumab/ipilimumab ± nivolumab maintenance), PD-1 inhibitor monotherapy (nivolumab or pembrolizumab), CTLA-4 inhibitor monotherapy (ipilimumab), and sequential CTLA-4 and PD-1 inhibitors, respectively. A total of 142 delayed irAEs were recorded in 94 (30%) pts. Median time to onset of delayed irAEs was 20.0 mo (12.2-80.6 mo). The most common delayed irAEs were dermatologic (27%), gastrointestinal (23%), and rheumatologic (20%). Most delayed irAEs were grade ≤2 (84%), but some were grade ≥3 (16%). Of individual delayed irAEs, 75 (51%) occurred on ICI treatment at time of onset, 39 (26%) after ≤3 mo of the last ICI cycle, and 34 (23%) after >3 mo of the last ICI cycle. 79 (56%) and 20 (14%) delayed irAEs were treated with systemic steroids and immunomodulators, respectively. Further, 12 (8%) delayed irAEs led to hospitalization, and 64 (45%) required subspecialty consultation. Pts with a history of autoimmune disease were more likely to have a delayed irAE (p=0.02), as were pts who achieved a partial or complete response (p=0.02). There was a trend towards a greater frequency of delayed irAEs in pts treated with PD-1 (37%) compared with combination (28%), CTLA-4 (11%), or sequential CTLA-4 and PD-1 (28%) (p=0.068). Conclusions: Delayed irAEs occurred in almost a third of pts with advanced melanoma treated with ICIs and followed for at least 1 year. Extended follow-up to monitor for delayed irAEs should be considered as many events required immunosuppressive therapy and rarely, may be life threatening. [Table: see text]
Systemic inflammation-modified PG-SGA index in the survival prediction of advanced cancers.
Authors: Min Yu , Dai Tingting , Li Xuemei , Cai Lei , Zhou Jitao , Peng Xingchen
Published: June 2024

12056

Background: The tight association between inflammation and nutrition has been established. Whether the systemic inflammatory indicators could increase the predictive power of nutrition assessment tools in the survival of advanced cancers remains unclear. Methods: In this retrospective study, advanced cancer patients were enrolled from the West China Hospital between Nov 2019 and Sep 2023. Five systemic inflammatory indicators were selected including the systemic inflammatory index (SII), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR), and advanced lung cancer inflammation index (ALI). Nutritional status was evaluated by the PG-SGA. Kaplan-Meier curves, restricted cubic splines (RCS), and Cox regression analyses were used to estimate the effects of systemic inflammation indices as well as systemic inflammation-modified PG-SGA index on the survival of cancer patients. Stratified and sensitive analyses were conducted to determine the high-risk subgroups and check the robustness of the main findings. Results: In total, there were 1,065 advanced-stage cancer patients included in this study, with a mean age of 58.18 years old. Advanced lung cancer (265 cases, 24.9%) accounted for relatively higher proportions of the whole study population, followed by colorectal cancer (167 cases, 15.7%), esophagus cancer (143 cases, 13.4%), and gastric cancer (139 cases, 13.0%). With a median follow-up of 1,300 days, 501 deaths (47.04%) were observed. Multivariate Cox regression analysis showed that ALI maintained the best predictive power in predicting the all-cause mortality of advanced-stage cancer patients when compared with other systemic inflammation indicators (4th quartile: hazard ratio (HR)= 0.38, 95% confidence interval (CI): 0.29, 0.50, P<0.001), with a C-index of 0.615. The novel inflammation-modified PG-SGA/ALI index showed better predictive value in identifying the high-risk subgroups of advanced-stage cancer patients, with an AUC of ROC of 0.68 in 365-day mortality, 0.65 in 730-day mortality, and 0.64 in 1300-day survival prediction, respectively. The C-index (0.626), calibration curves, and decision curve analysis validated the promising predictive accuracy of the PG-SGA/ALI index in predicting the all-cause mortality of advanced-stage cancer patients. No significant interaction was observed between subgroups. A series of sensitive analyses supported the consistent findings as we determined in the main regression. Conclusions: Our study highlights that the PG-SGA/ALI index has superior predictive value than original PG-SGA criteria in short- and long-term survival prediction of advanced cancers. The PG-SGA/ALI index would be a more accurate tool for nutritional evaluation and prognosis prediction among cancer patients during clinical practice.
Decades old communication training influences seen in patient-centric communication skills of transplant hematologists.
Authors: Hung Justine , Rodenbach Rachel , Campbell Toby Christopher
Published: June 2024

12099

Background: Competency in communication skills was added as a requirement for residencies in 1999. Numerous strategies have since been incorporated into all phases of medical education and beyond. “Ask-tell-ask” and “NURSE” are commonly taught strategies used to guide conversations between physicians and patients. “Ask-tell-ask” provides a structure for assessing and delivering medical knowledge to a patient. “NURSE” outlines methods for incorporating empathy into the medical provider’s statements. We evaluated for the presence of these communication strategies in a high-stakes discussion between a transplant hematologist and a simulated patient facing a new diagnosis of high-risk myelodysplastic syndrome (MDS). Methods: This is a sub-analysis from a mixed-methods, observational study. Our team recruited hematologists who routinely perform hematopoietic cell transplants and designed a patient scenario of a 67-year-old man with recently diagnosed high-risk MDS referred to hematology. Video-recorded virtual encounters simulated an initial hematology consultation appointment between the hematologist and an actor trained to portray the patient. We analyzed transcripts and coded for themes in the discussion content and structure. We evaluated for the use of known communication strategies “ask-tell-ask”, and “NURSE” empathic responses. Results: Of 37 hematologists from 25 academic centers who participated, 73% reported receiving at least some formal communication training. Hematologists ” when teaching patients about their disease and treatment options. For example, nearly all hematologists opened the encounter by asking the patient a perception question regarding their understanding of their disease; nearly all incorporated at least one "NURSE" empathic statement after telling the patient about their disease and its prognostic implications. Most explored the patient’s goals for treatment and described treatment options utilizing an “ask-tell-ask” approach. Nearly all concluded the encounter with a summary and strategy for next steps. Conclusions: While it is commonly held that teaching communication is difficult, these conversations between hematologists and patient actors show the impact of communication training delivered over the past twenty years through the routine incorporation of well-described strategies of “ask-tell-ask” and "NURSE". This observational study provides a window into how these teachings have permeated into medical practice and hematology/oncology specifically. The incorporation of commonly taught communication strategies into these physician-patient encounters provides evidence that teaching high-quality communication may change physician behavior in a sustained and diffuse way.
Enhancing early detection of lung cancer: A strategic initiative to boost screening rates among patients.
Authors: Galeas Jose Nahun , Huggins Tiffany , Sage Braden , Roy Josh , Hendricks Carolyn B.
Published: June 2024

e22512

Background: Lung cancer is the top cause of cancer death in the U.S. Despite LDCT screenings reducing mortality, uptake is low in Alabama and nationally (6% vs. 4.5%). The U.S. Preventive Services Task Force recommends annual LDCT for certain high-risk adults, but factors like awareness, access, and policy affect screening rates. Alabama's situation is worsened by rural disparities and socioeconomic issues. Infirmary Health is the largest private, not for profit health care system in the state of Alabama. This study focuses on evaluating LDCT screening in a selected clinic of our health care system, pinpointing obstacles to adherence, and seeking ways to boost screenings to lower lung cancer mortality through early detection. Methods: As part of the Summer 2023 ASCO Quality Training Program we adopted a QI approach to increase LDCT lung cancer screening. It began by assessing baseline screening rates and staff knowledge, then created problem and aim statements. The team conducted root cause analysis, used a Pareto chart for issue prioritization, and employed a Priority Pay-off Matrix to focus on impactful, feasible issues. The Plan-Do-Study-Act (PDSA) cycle was then used to develop, test, and implement interventions, ensuring strategic alignment and effective monitoring of outcomes to enhance screening rates. Results: From January to July 2023, the Infirmary Health -Hillcrest clinic had a low 10.53% LDCT screening rate (system wide 6%, this clinic was selected due to it's highest screening rate), leading to late-stage lung cancer diagnoses and higher mortality. To address this, a goal was set to triple the screening rate to 30% by December 2023. Key barriers identified were staff and patient knowledge about lung cancer screening and a cumbersome LDCT ordering process. A PDSA cycle initiated between September and December 2023, firstly focused on Patient/Clinic Education, increasing screening rates by simplifying the process—removing doctor signature requirements and enhancing staff knowledge through meetings and informative flyers. The subsequent phase introduced a Nurse Navigator, who further increased screenings through prescreening, staff reminders, and on-site visits. By December of 2023 the LDCT screening rate was increased from baseline 10.53% to 33.3%. Conclusions: Through identifying and addressing key issues like education, faulty process and nurse navigation we successfully elevated LDCT screening rates. This study highlights the benefit of participating in a structured quality training program. [Table: see text]