bluuebunny/crossref_metadata_2025 huggingface dataset:
Palliative care consultation and end-of-life outcomes in a retrospective cohort of patients treated with immune checkpoint inhibitors.
Authors: Bloomer Chance H. , Faucheux Andrew T. , Quattlebaum Alexander M. , Elko Catherine A. , Hunting John , Khoury Lara M. , Olson Eric , Omlor Rebecca , Lycan Thomas William
Published: June 2023

6577

Background: Immune checkpoint inhibitors (ICI) can prolong survival for various cancers and are generally available as treatment options for most patients because of their favorable adverse effect profile. Although ICIs provide treatment for many patients who would otherwise be out of options, their variable and often delayed efficacy may postpone the de-escalation of care at the end of life. Palliative Care consultation (PCC) is well-established among patients receiving cytotoxic chemotherapy, but its effectiveness is less certain among patients receiving newer treatment modalities. We aimed to test the association of PCC with end-of-life (EOL) outcomes among patients treated with an ICI for any type of cancer. Methods: We created a retrospective registry of all patients who received at least one dose of ICI for any indication between 2/1/2011 and 4/7/2022 at a comprehensive cancer center and its outreach clinics. The investigators created a secure, cloud-based registry (REDCap), validated it with data quality rules, and resolved all discrepancies; clinical research specialists at Vasta Global captured most of the data. We used the chi-square test to compare categorical variables, defined statistical significance as p < 0.05, and used SAS version 9.4 for analyses. The study had institutional IRB approval. Results: The cohort consisted of 3,142 patients with lung cancer (45%) as the most common cancer type, followed by melanoma (14%) and head and neck squamous cell carcinoma (9%). ICI was most often given in the first line setting (46%) with good baseline performance status (ECOG 0-1, 50%). 915 (29%) patients had PCC, which was associated with a higher rate of code status de-escalation from “Full Code” at any point before death (92% vs. 87%, p 0.007). There was no association between PCC and either the initiation of ICI within 30 days of death (7% vs. 5%, p .0172) or any dose of ICI within 14 days of death (5% vs. 6%, p 0.33). Among patients with a confirmed location of death (1013, 32%), PCC was associated with a similar rate of death in the hospital at any level of care (30% vs. 28%, p 0.51). Conclusions: PCC was associated with code status de-escalation before death but similar risks of late ICI dosing or inpatient status at the time of death. Further studies are needed to risk-stratify patients starting ICI to identify the subgroups that would benefit the most from PCC.
Breast cancer staging for patients with “low risk” disease: Are they all the same?
Authors: Plichta Jennifer Kay , Thomas Samantha M. , Record Sydney , Botty van den Bruele Astrid , Chiba Akiko , DiLalla Gayle , DiNome Maggie , Rosenberger Laura Horst , Woriax Hannah , Hwang Eun-Sil Shelley
Published: June 2023

6584

Background: Studies have shown that a low (<11) Oncotype DX recurrence score (RS) is associated with better survival outcomes. RS is currently included in the AJCC prognostic staging criteria. Not all patients with a low RS are downstaged. It has been suggested that a low RS should further downstage patients regardless of other disease factors. We explored survival outcomes for patients with a low RS to assess if additional patients should be downstaged. Methods: Using the National Cancer Database, female patients ages 18-75 with invasive unilateral pT1-3, pN0-1, M0 hormone receptor positive (ER+ and/or PR+), HER2- breast cancer and a RS <11, diagnosed 2010-2018 were identified. Patients who received neoadjuvant treatment were excluded. Patients were grouped based on the AJCC 8th edition prognostic stage (IA, IB, IIA, IIB, IIIA). Variables were summarized, and unadjusted overall survival (OS) was estimated using the Kaplan-Meier method. Cox proportional hazards models were used to estimate the association of stage with OS after adjustment for available covariates. Results: Of the 54,961 patients with a RS <11, median follow-up was 57.7 months (95% CI 57.3-58.1), and median age was 61yo (IQR 52-67). Most tumors were grade 1 (37.6%) or 2 (56.9%) with ductal histology (75.3%). The median tumor size was 1.5 cm (IQR 1-2), and most were pN0 (83.3%). Although most patients with a RS <11 were stage IA (94.2%), some had a higher stage assignment (5.1% stage IB, 0.6% IIA, 0.1% IIB, <0.01% IIIA). Most patients (93.4%) received endocrine therapy (ET), and few (3%) received chemotherapy. Patients treated with chemotherapy more often had younger age, lobular histology, higher grade, larger tumor size, and/or pN+ disease (all p<0.001). Unadjusted OS was reduced with higher stage (log-rank p<0.001), and this remained true when limited to only those who received ET without chemotherapy (log-rank p<0.001). After adjustment for relevant covariates including treatment, higher stage remained associated with worse OS [stage IA: ref; IB: HR 1.66 (95% CI 1.34-2.05); IIA: HR 2.29 (95% CI 1.44-3.65); IIB: HR 2.48 (95% CI 1.03-5.95); overall p<0.001]. Conclusions: For patients with a low RS, survival outcomes vary with current AJCC prognostic disease stage, suggesting that not all patients with a RS <11 should be downstaged based on RS alone. Anatomic and other non-genomic factors remain relevant when assessing prognosis. [Table: see text]
Trends in the use of maintenance therapy in ovarian cancer.
Authors: Adjei Naomi N. , Haas Allen , Zhao Hui , Primm Kristin Marianne , Sun Charlotte C. , Meyer Larissa Alejandra
Published: June 2023

6585

Background: Emerging maintenance therapies in advanced ovarian cancer (OC) remain of high interest since 70% of patients (pts) will relapse and ultimately succumb to OC. This study analyzes nonclinical factors associated with maintenance therapy (MT) in OC. We define MT in OC as the use of polyADP-ribose polymerase inhibitors (PARPi) and/or bevacizumab (bev) following platinum-based chemotherapy. Methods: We used data from Optum’s de-identified Clinformatics Data Mart Database F to conduct an analysis of OC pts with Medicare or commercial health insurance. Pts were included if they had 1 inpatient or 2 outpatient diagnosis codes for OC from 01/2017 to 12/2020 and received platinum-based chemotherapy after diagnosis. Pts were excluded if they did not have continuous coverage from diagnosis until 6 months after completion of platinum-based chemotherapy or death. MT was identified by insurance claims for PARPi or bev received within 6 months after completion of platinum-based chemotherapy. Descriptive statistics were used to summarize patient characteristics. Multivariable logistic regression was used to evaluate associations between pts’ nonclinical characteristics and MT use. Trends in MT use were reviewed by year. Subgroup analysis comparing trends in PARPi use to bev use was also performed. The median time from last chemotherapy until initiation of MT was 22 days. Results: 5,652 pts were included in the study with a median age of 70 years. The majority were white (70.7%), Medicare-insured (71.8%), and treated in the South (42.8%). 33.6% of pts received MT and 66.4% of pts received neither PARPi nor bev. More pts received bev alone (19.6%) compared to PARPi alone (10.3%) or combination MT (3.7%). Olaparib was the most commonly prescribed PARPi. After adjusting for insurance type, both PARPi and bev use increased significantly over time from 2017 to 2021. Pts with more comorbidity burdens (i.e. higher Elixhauser comorbidity index) were more likely to receive MT compared to pts with less comorbidity [OR (95% CI): 1.44 (1.26-1.65)]. MT use was significantly associated with treatment in the South compared to the Northeast [1.22(1.01-1.46)] and younger age, pts > 76 years were less likely to use MT compared to pts < 56 years old [0.78 (0.62-0.98)]. In the subgroup analysis, PARPi use was significantly associated with age, race and region compared with no MT use, while bev use was not associated with these factors. Conclusions: Age, comorbidity status, and geographic location of treatment were associated with MT use. The increasing use of MT over time is consistent with published data since both agents have demonstrated a progression free survival advantage and have tolerable toxicity profiles. With increasing focus on MT in OC, a better understanding of nonclinical factors associated with MT use is imperative to eliminating potential disparities in OC outcomes.
Site of metastasis (SoM) and its impact on clinical outcomes in 8 cancer cohorts.
Authors: George Rohini , Singh Neeraj , Vidal Laura , Hajek Ewa , Skalska Dorota , Saini Kamal S. , Agrawal Smita
Published: June 2023

6590

Background: The prognosis of metastatic cancer is in general poor. This can be affected by several factors including age, histology, treatment choices & SoM etc. Methods: This retrospective study leverages ConcertAI’s deeply curated Patient360 datasets for 8 solid cancers to assess the impact of SoM on the outcomes of patients. For the purpose of this analysis, we focused on the most common SoM (bone, brain, lung & liver). Patients had either a Single SoM (SSM) or Multiple SoM (MSM) and we focused this analysis on patients with SSM. The overall survival (OS) & progression free survival (PFS) from the date of metastasis as well as the time to metastasis (TTM) from initial diagnosis were determined for each cohort. We also computed a consolidated OS & PFS for all patients with MSM. Results: 140K patients were included in this study of which 60K patients had a SoM. The distribution of SoM is dependent on the primary cancer type. For example, in breast & prostate cancer, bone metastasis accounts for 50-80 % of the metastatic cohort whereas it is only 8-21% in lung & melanoma. As expected, the overall values of OS/PFS were primarily governed by the primary cancer type (Table), but this analysis provides further interesting insights: 1. Within a cohort, there were significant differences in the prognosis of patients based on the SoM . Brain & liver had a poorer prognosis compared to the other SoM across most cohorts. 2. The relative prognosis for some SoM were dependant on the primary cancer type. For example, there was a very significant difference between the OS/PFS values in the breast cancer cohort when comparing brain vs bone as SoM. However, in the lung cancer cohort, this difference was less pronounced, and the trend was flipped. 3. For some cohorts the SSM for certain sites had a worse prognosis than the MSM. In breast cancer the OS of the brain & liver SoM was worse than the MSM. 4. The TTM is also dependent on the primary cancer and there is a correlation between the average TTM and the OS of the cohort. Conclusions: The patterns of cancer metastasis and the absolute and relative prognosis for a particular SoM is dependent on the primary cancer type. Such insights from a large real-world data study can impact clinical decisions regarding the aggressiveness of treatment based on the primary cancer type as well as the metastatic site. [Table: see text]
Malnutrition risk at diagnosis and influence on survival in patients with solid tumors at a large academic cancer center.
Authors: Kadakia Kunal C. , Symanowski James Thomas , Aktas Aynur , Szafranski Michele , Salo Jonathan C. , Meadors Patrick L. , Aung Ye Myint , Walsh Declan
Published: June 2023

6591

Background: Malnutrition is common in cancer patients and negatively impacts quality of life, tolerance to anti-cancer therapies and is associated with poor prognosis. It is, however, unclear if patient-reported malnutrition risk at initial diagnosis is related to overall survival (OS) in solid tumor oncology outpatients in the United States. Methods: A cohort of 3,562 patients who completed the malnutrition screening tool (MST), a validated assessment of malnutrition risk, at initial diagnosis of any stage solid tumor and had available survival data were analyzed. The primary objective was to evaluate the relationship of high malnutrition risk (≥2 of 5 = high risk for malnutrition, H-MST) to OS and was assessed using Kaplan Meier techniques and Cox proportional hazards models. Unadjusted analyses were performed, and adjusted multivariable analyses evaluated the impact of H-MST on OS controlling for key clinical baseline confounders. Results: The median age was 63 years (IQR: 54-71), with 62% females and 81% White. Most common cancer sites were breast (28%), gastrointestinal (GI, 21%), and thoracic (13%) and 80% were non-metastatic. Median follow up was 48.3 months. H-MST was associated with lower OS in the unadjusted model, median OS in months was 32.5 [H-MST] vs not reached in low MST [L-MST] (HR 3.3, 95% CI 2.9-3.7, p = < 0.001). Multivariable analysis confirmed that H-MST remained independently associated with OS when controlling for age, sex, cancer site, stage, BMI, and symptom scores. Landmark OS rates at 50 months were 60% [H-MST] vs. 69% [L-MST] (HR 1.51 95% CI 1.3-1.7, p = < 0.001). Adjusted subgroup analyses by cancer site showed the independent impact of H-MST was relatively similar across groups (Table). Conclusions: High malnutrition risk at initial diagnosis was independently associated with shorter survival across a large representative cohort of solid tumor oncology outpatients. The screening occurred before any anti-cancer therapy and it is noteworthy most had non-metastatic disease. These data highlight the need for systematic screening to identify patients at malnutrition risk who need additional assessment early during cancer. Further research on how to optimize allocation of limited nutrition resources for those with high malnutrition risk is needed. [Table: see text]
Tumor lysis syndrome in solid tumors: A retrospective cohort study of the National Inpatient Sample from 2016 to 2019.
Authors: Chitkara Akshit , Khosla Akshita , Anamika Fnu , Raj Kavin , Koka Jean-marie , Ramaswamy Bhuvaneswari
Published: June 2023

6594

Background: Tumor lysis syndrome (TLS) is a life-threatening oncologic emergency. Patients with a rapidly proliferating tumor or high tumor burden after cytotoxic chemotherapy, predominantly in hematologic malignancies, are at increased risk of TLS. The advancement in therapeutic strategies of oncology in the past few decades has expanded the spectrum of malignancies associated with TLS. A dearth of literature on the incidence of TLS in various solid malignancies exists. Using the National Inpatient Sample (NIS) data, this study aims to highlight the solid malignancies at risk of TLS, highlight the demographic factors, and draw a comparison with that in hematological malignancies. Methods: The NIS 2016-2019 dataset was analyzed utilizing univariate and multivariate logistic regression analysis for the predictors of TLS (P <0.05). StataCorp. 2021. Release 17. College Station, TX: StataCorp LLC, BE version with Stata’s svy command, and appropriate weights, were used to perform the analysis. The overall fit was analyzed using Receiver Operative Curves (ROC), and sensitivity analysis was analyzed using the e-value package. Results: From 2016-2019, a total of 51,385 (48,917-53,853) hospitalizations had an incidence of TLS. We included 16,249 cases of TLS in patients treated for the ten most common malignancies in the US. We found that older age, male sex, and black race were associated with higher odds of TLS. It was reported highest in large hospitals and urban non-teaching hospitals. The regional distribution of the TLS suggests the highest odds in the Western region. The odds of getting TLS were highest among Leukemias and Lymphomas, respectively. Among solid tumors, the odds of getting TLS were highest in uterine cancer patients, followed by lung, breast, pancreatic, and liver cancer among the top five. (Table). Conclusions: In this study, we conclude that solid tumors, mainly uterine, followed by lung and breast, have significantly higher odds of TLS, more so in larger or non-teaching hospitals. There is a need to establish specific management guidelines to prevent these TLS cases that will improve the morbidity and mortality associated with TLS and help build more cost-effective treatment regimens. [Table: see text]
Real-world response endpoints in patients with mNSCLC treated with chemotherapy across real-world datasets.
Authors: McKelvey Brittany Avin , Garrett-Mayer Elizabeth , Belli Andrew J. , Brown Thomas D. , Dow Jessica , Espirito Janet L. , Kluetz Paul , Ma Xinran , McCracken Andrea , Mishra-Kalyani Pallavi Shruti , Natanzon Yanina , Potter Danielle , Rivera Donna , Stires Hillary , Stewart Mark , Allen Jeff
Published: June 2023

6595

Background: Response Evaluation Criteria in Solid Tumors (RECIST) based response rate (RR) is used for efficacy evaluation in clinical trials and relies on imaging data collected at specified timepoints for uniform assessment. In routine clinical practice, the method and timing of response assessment can vary, and imaging data from electronic health records (EHR) and other real world (rw) sources may not be available, making RECIST-based assessment of rw-response rate (rwRR) using rw data (RWD) challenging. Friends of Cancer Research formed a multi-stakeholder partnership to assess available data attributes to measure response across RWD sources to inform development of a consistent method for measurement. Methods: The study included seven EHR data partners who identified and analyzed a cohort of 1,380 patients (pts) with metastatic non-small cell lung cancer (mNSCLC) treated with first-line platinum doublet chemotherapy, following a common protocol and statistical analysis plan. The availability and frequency of data components to assess response including raw images, radiology imaging reports, and clinician response assessments from provider notes were assessed. Response endpoints measured included rwRR, rw-duration of response (rwDOR), and the association of rwR with rw-overall survival (rwOS), rw-time to treatment discontinuation (rwTTD), and rw-time to next treatment (rwTTNT). Results: The availability of data components varied across RWD sources (Table). Images were not widely accessible, thus response was analyzed using clinician response assessments (median proportion of pts evaluable, 77.5%). Of these assessments, the majority relied on imaging interpretation. The median rwRR was 46% with a median rwDOR of 119 days. The table provides median rwTTD, rwTTNT, and rwOS across data sources. Conclusions: The rwRR among pts with mNSCLC calculated using the clinician assessment was relatively consistent across all RWD sources, with consistent trends in time to event endpoints. While variability in the availability of data components to assess response was observed, the demonstrated feasibility of response endpoints based on clinician assessment suggests further exploration may inform drug effectiveness evaluation with RWD. [Table: see text]
Molecular testing utilization in patients with advanced non-small cell lung cancer (NSCLC) in Washington (WA) state.
Authors: Shih Lauren , Sun Qin , Fedorenko Catherine R. , Yu Kaiyue , Li Li , Kreizenbeck Karma L. , Shankaran Veena , Ramsey Scott David
Published: June 2023

6596

Background: Therapies targeted at driver mutations (e.g. EGFR, ALK) in NSCLC have contributed to improved patient survival. While current guidelines recommend that all patients diagnosed with stage IV NSCLC undergo molecular testing to determine eligibility for targeted therapies, real-world testing patterns have not been well described. In a retrospective study using cancer registry and insurance claims, we evaluated rates of molecular testing in a population-based sample of NSCLC patients in WA. Methods: We linked WA state cancer registry records from 2017-2019 with claims records for Medicare, Medicaid, and two large commercial insurers. Patients diagnosed with stage IV NSCLC who had continuous insurance enrollment for 2 months prior to and 12 months following diagnosis were identified. Using insurance claims data, we identified patients who received any molecular testing (either testing for specific markers or comprehensive molecular profiling). We compared proportions of patients who received and did not receive molecular testing by insurance type, race, ethnicity, gender, and diagnosis (Dx) year. We performed a multivariate regression analysis to determine factors associated with completion of molecular testing. Results: 1048 eligible patients were identified. The median age was 70. Patients were predominately insured by Medicare (62.6%) and non-Hispanic white. 90.3% of all patients underwent molecular testing. Molecular testing rates were similar between white and non-white patients (90.4% vs 89.2%, p=0.647). Testing rates were significantly lower among Hispanic patients vs non-Hispanic patients (77.8% vs 90.7%, p=0.018). Testing rates were lowest among Medicaid enrollees (86.4%) compared to Medicare (88.4%), commercial (97.2%) or multiple insurances (94.9%) (p=0.0018). A multivariate analysis demonstrated that patients age ≥65 and Medicaid patients were less likely to receive molecular testing while females were more likely to receive testing; year of Dx did not impact testing rates (Table). Conclusions: While the rate of adherence to recommended molecular testing was high in the overall cohort, testing rates were lower in Hispanic patients, older patients, males, and those with Medicaid insurance. Given the therapeutic implications of testing, drivers of these observed disparities warrant further study to ensure equitable access to efficacious treatment. [Table: see text]
Disparities in PI3K/mTOR inhibitor use, toxicities, and outcomes among patients with metastatic breast cancer.
Authors: Sathe Claire , Accordino Melissa Kate , DeStephano David , Shah Mansi , Wright Jason Dennis , Hershman Dawn L.
Published: June 2023

6597

Background: Advances in breast cancer treatment have led to improvements in survival among patients with metastatic breast cancer (MBC). Nevertheless, Black patients and patients with lower socioeconomic status (SES) continue to bear a disproportionate mortality burden. Furthermore, because landmark trials for novel anticancer agents lacked racial diversity, their toxicity profile for minority patients remains uncertain. Our study examines the impact of race and other sociodemographic characteristics in the use and toxicity outcomes of PI3K and mTOR inhibitors (PI3K/mTORi). Methods: We conducted a retrospective analysis of EHR-derived data from the Flatiron Health Database (FHD). A dataset was constructed to include patients with hormone receptor-positive, HER2-negative MBC diagnosed between 1/1/2011 and 1/31/2022. Outcomes included PI3K/mTORi use, rates of hyperglycemia and dose reduction, and time on treatment. Multivariable logistic regression was used to evaluate factors associated with use and outcomes. Results: A total of 13,388 patients with MBC were included in our analysis, of which 2,620 (19.6%) received PI3K/mTORi (78.3% everolimus, 14.7% alpelisib, 6.9% both agents). Overall, 67.5% of all patients were categorized as White, 9.8% as Black/African-American (Black/AA); 18.9% were >75 years old; 10.1% were treated at an academic site; 4.0% had Medicaid insurance. Insurance through Medicaid was associated with lower use of PI3K/mTORi compared to commercial insurance (15.6% vs 18.8%; OR: 0.76, 95% CI: 0.59-0.99, p=0.04), as was advanced age (10.9% for >75 years old vs 22.9% for <60 years old; OR: 0.68, 95% CI: 0.58-0.80, p<0.001) and poorer performance status at diagnosis (15.1% for ECOG ≥2+ vs 22.9% for ECOG 0; OR: 0.84, CI: 0.72-0.98, p=0.03). Odds of PI3K/mTORi use were almost 50% higher for patients treated at an academic center (OR: 1.46, CI: 1.06-2.05, p=0.02). While Black/AA patient had lower rates of use than White patients (17.4% vs 20.1%), they had similar odds of receiving PI3K/mTORi on multivariable analysis (OR: 1.00, CI: 0.85-1.17, p>0.9). Black/AA patients experienced higher rates of hyperglycemia on PI3K/mTORi than White patients (67.6% vs 52.5%). On multivariable analysis, odds of hyperglycemia were twice as high for Black/AA patients (OR: 2.1, CI: 1.33-3.35, p<0.01). However, rates of dose reductions and time on PI3K/mTORi therapy did not differ significantly among White vs Black/AA patients. Conclusions: This analysis of real-world data suggests that lower SES is associated with decreased PI3K/mTORi use. Efforts to improve access to these life-prolonging agents are warranted. Of concern, we also found racial disparities in toxicity outcomes, with Black patients having twice the risk of hyperglycemia. Greater attention to the tolerability of novel agents in diverse populations is warranted.
Decomposing racial differences in financial hardship among older cancer survivors.
Authors: Davis Elizabeth , Yarbro Alaina , Bhatia Smita , Kenzik Kelly
Published: June 2023

6598

Background: Despite Medicare coverage, financial hardship is a prevalent issue among older cancer survivors, particularly among those belonging to a racial/ethnic minority. Sociodemographic, clinical, and area-level factors may mediate this relationship; however, no studies have assessed the extent to which these factors contribute to disparities. Methods: Surveys assessing financial hardship after cancer were completed by 721 patients age 65y+ of Black or white race completing primary cancer treatment for breast, prostate, colorectal, prostate cancer or lymphoma at University of Alabama at Birmingham between 2000 and 2019. Financial hardship included material, psychological, and behavioral domains. Material hardship included ever 1) borrowing money/going into debt, 2) filed for bankruptcy, 3) worried about paying large medical bills, and 4) made any other financial sacrifices due to cancer. Psychological hardship was measured by asking if participants were ever worried about paying large medical bills related to cancer, its treatment or effects of treatment. Behavioral hardship was measured by asking if participants were unable or delayed in obtaining medical care, tests, treatments or prescriptions in the last 6 months. Non-linear Blinder-Oaxaca effect decomposition methods evaluated the extent to which individual-level sociodemographic, clinical, and area-level factors contributed to racial disparities in financial hardship. Results: Median age at survey was 78 (IQR = 73-82), majority were female (53%) and non-Hispanic White (84%). The most common cancers were breast (34%) and prostate (27%), followed by lung (17%), lymphoma (9%) and colorectal (14%). Ninety percent were diagnosed at an early stage and median time from diagnosis to survey was 8y (IQR = 5-12). There were no significant clinical differences between Black and white patients. Overall, 22% reported any financial hardship; 14% material, 3% behavioral, and 14% psychological. Black, compared to White participants reported significantly (p < 0.001) higher rates of overall (39% v 18%), material (29% v 11%), and psychological (27% v 11%) financial hardship. Notably, Black patients had higher rates of being unable to cover cancer-related costs (23% v 7%), worrying about paying large medical bills (27% v 11%), and having to borrow money or go into debt (9% v 3%). Overall, the observed characteristics explained 81% of racial differences in financial hardship among cancer survivors, primarily by differences in income (24%), cancer diagnosis and stage (22%), and area deprivation (15%). Conclusions: These results identify primary contributors to racial disparities in financial hardship among older cancer survivors, which can be used to develop interventions aimed at eliminating inferior healthcare outcomes experienced by certain racial groups, inform policy, and allocate resources to those at greatest risk for financial hardship.
Intrathecal drug delivery systems for cancer pain control: Insights on current contemporary practices in the US.
Authors: Goel Vasudha , Geller Melissa Ann , Blaes Anne Hudson , Gulati Amitabh
Published: June 2023

6605

Background: About a third of cancer survivors report moderate to severe pain. Intrathecal drug delivery system (IDDS) is an implantable pain control option for treating intractable chronic pain not responsive to systemic opioid therapy. Studies on the current practices in the US around the utilization of IDDS for cancer pain are lacking. Methods: The Nationwide inpatient sample (NIS) dataset is funded by the Agency for healthcare research and quality (AHRQ) for multistate healthcare research & decision-making. Adult patients admitted to hospitals with a primary or secondary cancer diagnosis between 2016-19 were included. Patients undergoing IDDS implantation were identified using the validated International Classification of Diseases, 10th Revision, Procedure Coding System codes (00HU33Z Insertion of infusion device into spinal canal, percutaneous approach and 0JH80VZ Insertion of infusion pump into abdomen subcutaneous tissue and fascia, open). Baseline demographics, hospital characteristics, and type of cancer associated with IDDS implantation were evaluated in the study. Results: 22,895 patients underwent IDDS surgery amongst 7.06 million hospitalizations from 2016-19. The IDDS cohort consisted of patients in the 65-79 years age group (40.49%), female sex (50.42%), and Caucasian ethnicity (75.82%). Most IDDS surgeries were performed in large, urban teaching hospitals. Conclusions: Despite recommendations supporting IDDS use, a small minority received the treatment with significant racial & socioeconomic disparities in IDDS use. [Table: see text]
Development of natural language processing (NLP) models for extracting key features from unstructured notes to create real-world data (RWD) assets for clinical research at scale.
Authors: Agrawal Smita , George Rohini , Vaidya Vivek Prabhakar , Chakkrapani Sangavai , Prajapati Rambaksh , Tankala Srikanth , Parmar Dhaval , Lakkimsetty Vinay Phani Santosh , Bhardwaj Tapasya , Ashwani Ashwani , Mendonca Emma , Narayanan Babu , Swaminathan Krishna Kumar , Mukherjee Pranay
Published: June 2023

6607

Background: RWD derived from Electronic Health Records (EHR) has detailed clinical information about patient journeys that can assist in clinical research, trial design, safety assessments etc. However, much of the vital information is locked away in unstructured clinical texts and needs to be converted to structured format to be useful for downstream applications. We demonstrate how this can be achieved at scale with a high degree of accuracy through NLP. Methods: NLP models were developed to extract data for 11 clinical variables from unstructured notes of ~98k lung cancer patients and merged with the structured data into a common data model (Table). These models were a combination of domain knowledge, rule-based models, machine learning models, and deep learning models. The increase in fill rate per variable over structured data only was used to quantify the improvement by NLP. The accuracy of the models was assessed against a manually curated dataset comprising of 752 patients. Results: The NLP models significantly improved the fill rate of key clinical variables and were able to extract the information from clinical notes with high accuracy (Table). For some variables such as NSCLC/SCLC status, surgery, tumor grade and histology, all or most of the data was extracted via NLP. Metastatic status via NLP included distant metastasis, locally advanced disease and no metastasis whereas in the structured data, only data for distant metastasis was present. In the case of Performance Status (PS), even though a significant number of patients had at least 1 PS recorded in the structured data, NLP significantly increased longitudinal capture, thus increasing the density of this variable per patient. Conclusions: NLP models can be developed and used to enrich structured RWD data by extracting information from unstructured documents thus significantly improving the utility of this data for downstream applications. Given the high accuracy of these models and the scale at which they can be run, this can be a good alternative to human curation or can augment human curation enabling the creation of very large-scale datasets for clinical research. [Table: see text]
Using real-world evidence (RWE) in regulatory decision making: A study of 6 oncology approvals with RWE included in the product label.
Authors: Zong Jihong , Jiao Xiaolong , Pan Lucy , Castelo Sarah , Campbell Chelsey , Lennert Barb , Bruno Amanda
Published: June 2023

6611

Background: The 21st Century Cures Act in 2016 enhanced the FDA’s ability to include the use of real-world data (RWD) and consideration of RWE in the development and approval of new medical products. Currently, limited assessments of the use of RWE in FDA approved oncology product reviews exist in the literature. This study was conducted to determine how RWE was used in FDA decisions for oncology drug approvals between 2015 and 2022. Methods: A systematic review of FDA submission documents and product labels available on the FDA website from 2020 to 2022, in addition to an exhaustive manual search of grey literature and the results of a targeted literature search from 2015 to 2019 were used to identify RWE that were included in FDA submission documents and in approved product labels. Results: In total, 124 oncology product evaluations were reviewed in the 2020 to 2022 literature search. Twenty-nine oncology product NDAs and BLAs included RWE to support efficacy, safety, or indication, of which the majority (n=26) ultimately had RWE accepted as evidence by the FDA for the submission. In these cases, RWE was used to add context (n=16), to support the indication or safety (n=7), to provide substantial basis for indication or safety (n=2), as a statistical comparison (n=2), or for informational purposes only (n=1). Feedback from the FDA reviewers for reasons RWE studies were not considered during product approval reviews included methodology issues, sample size concerns, and omission of patient level data. Ultimately, across the 2015 to 2019 targeted literature review and the 2020 to 2022 FDA submission document review, 6 oncology product labels incorporated RWE: palbociclib, uridine triacetate, lutetium Lu 177 DOTATATE, bevacizumab-adcd, naxitamab-gqgk, and decitabine/cedazuridine. RWE was used to support the initial indication for the majority of products (n=5) and also supported label expansion (n=1). RWE was incorporated in the product label postmarketing experience section (n=3), the clinical studies section (n=2), and the warnings/precautions section (n=1). Conclusions: These results suggest that RWE has become an important part of regulatory decision-making for oncology drug approval. Twenty-six of 29 RWE studies were accepted as evidence for the submission. For the 6 oncology products that include RWE in the product label, RWE was most frequently used to support the initial indication and was included in the postmarketing experience section. These examples show consistent use of RWE since the approval of the 21st Century Cares Act and provide evidence of a promising new direction with the creation of the FDA guideline/program for RWE.
Racial disparities in survival and stage at diagnosis among adolescent and young adult patients with cancer.
Authors: Taparra Kekoa A. , Kekumano Kāʻeo , Benevente Ryan , Gimmen Megan Y. , Kinslow Connon , Deville Curtiland , Pollom Erqi L.
Published: June 2023

6615

Background: Adolescent and young adult (AYA) patients (15-39 years) are an underrecognized population with high risk of select malignancies. Compared to pediatric and adult patients, AYA patients have not achieved improvements in cancer survival. No studies have evaluated overall survival (OS) and stage at diagnosis among all 5 federally recognized races in the US. Here we aim to investigate OS and stage at diagnosis among AYA patients by race. Methods: A retrospective cohort study of AYA patients diagnosed between 2004-2017 was conducted with the National Cancer Database. Patients with the 10 deadliest AYA cancers with at least 6 months of follow-up were included. Primary endpoints were OS (time from diagnosis to death) and late stage at diagnosis (stage III/IV or Grade III/IV for central nervous system [CNS] cancer). Kaplan-Meier estimates and log-rank tests assessed OS. OS and late stage were evaluated by race using multivariable Cox proportional hazard (adjusted hazard ratio [aHR]) and logistic (adjusted odds ratio [aOR]) regressions, respectively, with 95% confidence intervals (95%CI). All regressions were adjusted for sociodemographic and cancer characteristics. Results: 291,899 AYA patients were included: 64% female, 65% stage I/II, and 62 month median follow-up. Cancer sites included 27% breast, 16% lymphoma, 13% melanoma, 11% testis, 9% CNS, 7% colorectal, 7% cervix, 5% sarcoma, 3% ovary, and 2% lung. Race included 82.3% Non-Hispanic White (NHW), 14.0% Black, 2.9% Asian, 0.5% American Indian and Alaska Native (AIAN), and 0.3% Native Hawaiian and other Pacific Islander (NHPI). OS differed for all cancers by race (p<.0001), except for lung (p=.008), CNS (p=.32), and ovary (p=.28). OS was significantly inferior for NHPI, Black, and AIAN but superior for Asian, versus NHW (Table). NHPI had inferior OS (aHR, 95%CI) for melanoma (4.5, 2.0-10.0), colorectal (1.8, 1.3-2.4), lymphoma (1.7, 1.1-2.1), and cervix (1.6, .1-2.4) cancers. Black patients had inferior OS for melanoma (1.6, 1.2-2.2), lymphoma (1.5, 1.4-1.6), and breast (1.4, 1.3-1.4) cancers. Asian patients had superior OS for breast (0.7, 0.7-0.8) and lung (0.7, 0.6-0.9) but inferior survival for testis (1.9, 1.3-2.9) cancers. AIAN patients had inferior OS for colorectal (1.4, 1.0-1.9). Late stage at diagnosis was higher for NHPI, Black, and Asian patients, compared to NHW patients (Table). Conclusions: Both NHPI and Black AYA patients with cancer have higher risk of death and late stage disease at diagnosis, compared to NHW patients. Our data reveal racial disparities among Indigenous AYA patients masked by prior data omission. [Table: see text]
Real-world outcomes of patients (pts) with malignant solid tumors treated with immune checkpoint inhibitors (ICI) in relation to smoking status: The SAKK 80/19 SMOKER study.
Authors: El Saadany Tämer , Petrausch Ulf , Rojas Mora Alfonso , Winder Thomas , Renner Christoph , Benda Magdalena , Reimann Patrick , Froesch Patrizia , Jakob Andreas , Clavijo Daza Adriana , Müller Gisela , Von Moos Roger Anton Fredy , Mark Michael Thomas
Published: June 2023

6619

Background: ICIs are the standard of care for the treatment of different advanced solid organ tumors. Especially in advanced non-small-cell lung cancer, never-smokers were shown to have an inferior outcome when compared to ex-smokers/smokers, suggesting that the smoking status could be a predictive marker for survival benefits under ICI treatment. Methods: Pts within the Swiss Alpine Tumor Immunology Registry (AlpineTIR) treated with an ICI were differentiated by their smoking status (ex-smokers/smokers versus never-smokers). Overall survival (OS) and progression-free survival (PFS) from the start of the first ICI treatment were analyzed by smoking status. Further, subgroup analyses for OS and PFS were done for the most common disease entities. Results: A total of 702 pts were included, from which 455 pts (65%) were ex-smokers/smokers, 213 pts (30%) were never smokers, and 34 pts (5%) had an unknown smoking status. The median follow-up time from the administration of the first ICI to the statistical analysis was 2.7 years (95% CI: 2.3 to 3.2 years). The most frequent tumors were lung cancer (50%), melanoma (13%), renal cell cancer (7%), bladder cancer (6%), and others (24%). Across all indications, the median OS was 1.7 years (95% CI: 1.4 to 2.6 years) for never-smokers (n = 213) and 1.5 years (95% CI: 1.2 to 1.8 years) for smokers (n = 455) (HR: 1.10, 95% CI: 0.89 - 1.37). The median PFS was 6.3 months (95% CI: 4.4 to 8.3 months) for non-smokers and 6.2 months (95% CI: 5.2 to 7.0 months) for smokers (HR: 1.05, 95% CI: 0.87 - 1.27). In lung cancer pts, the median OS was 1.4 years (95% CI: 0.8 to 2.8 years) for never-smokers (n = 43) and 1.4 years (95% CI: 1.2 to 1.7 years) for smokers (n = 302) (HR: 1.02, 95% CI: 0.68 - 1.51). In melanoma pts, the median OS was 3.4 years (95% CI: 1.8 to not reached (NR) years) for never-smokers (n = 54) and 1.7 years (95% CI: 0.8 to NR years) for smokers (n = 34) (HR: 1.35, 95% CI: 0.72 - 2.53). In renal cell cancer pts, the median OS was 1.5 years (95% CI: 1.0 to 3.6 years) for never-smokers (n = 28) and 3.5 years (95% CI: 0.6 to NR years) for smokers (n= 17) (HR: 0.74, 95% CI: 0.31 - 1.78). In bladder cancer pts, the median OS was 1.8 years (95% CI: 0.6 to NR years) for never-smokers (n = 17) and 1.4 years (95% CI: 0.5 to NR years) for smokers (n = 26) (HR: 0.88, 95% CI: 0.39 - 1.99). Conclusions: No survival difference between smokers and non-smokers with metastatic solid organ tumors treated with ICIs could be detected. Interestingly, even in the subgroup of lung cancer pts, no difference was seen. Based on these data, the smoking status should not guide ICI treatment decisions.
Rates of emergency department visits and acute-care hospital admissions after starting chemotherapy or having surgery across six community-based cancer centers.
Authors: Hassett Michael J. , Cronin Christine , Tramontano Angela , Wong Sandra L. , Uno Hajime , Paudel Roshan , Bian Jessica J , Dizon Don S. , Hazard-Jenkins Hannah W. , Osarogiagbon Raymond U. , Schrag Deborah
Published: June 2023

6621

Background: Cancer patients who start chemotherapy or have surgery are at risk for serious adverse events, which can include emergency department visits (EDV) and acute-care hospital admissions (ADM). These events are relevant to patients, clinicians, health systems, and policy makers. Few studies have described the frequency and predictors of EDVs and ADMs in the routine care setting. We sought to address this knowledge gap, and to describe the impact of the COVID pandemic on these events, using data from the SIMPRO consortium of six US-based health systems. Methods: In 2019, SIMPRO started a phased deployment of an electronic health record-integrated symptom management program (eSyM) as part of the routine care provided to patients with a suspected or confirmed gastrointestinal, thoracic, and gynecologic malignancy. eSyM prompts patients to complete symptom questionnaires and provides symptom management resources for 180 days after starting chemotherapy and 60 days following surgery. This analysis includes all patients, whether they used eSyM resources or not. Outcomes, which were measured using EHR-based encounter data, included the rates of EDVs and ADMs at 30 and 90-days after starting chemotherapy or following discharge from surgery. To account for potential confounding, we used multivariable logistic regression for the 30-day outcomes and Cox regression for the 90-day outcomes. Results: From September 2019-December 2022, 8664 patients started chemotherapy and 11,578 had surgery, with 3075 and 2587 patients, respectively, experiencing at least one outcome event (Table). 90-day outcomes varied significantly across health systems for chemotherapy (EDV 2-21%, ADM 5-28%) and surgery (EDV 7-14%, ADM 9-18%) patients. In multivariable analyses, patients who reported an employment status of disabled were more likely to report an EDV (OR 1.73-1.96) and an ADM (ORs 1.52-1.96). Widowed status was associated with greater odds of having an ADM (ORs 1.29-1.30), but not an EDV. Cox regression found chemotherapy recipients experienced lower hazards of an EDV, but not an ADM, during 2020 (coinciding with the start of the COVID pandemic). For surgery patients, there was no significant association between calendar year and EDVs or ADMs. [p<0.001 for all reported values]. Conclusions: A meaningful proportion of patients who started chemotherapy or had surgery for a suspected or confirmed malignancy in the routine-care setting had an EDV or ADM within 90 days. Most events occurred within 30 days. Further work is required to ascertain how many of these encounters are avoidable and what structural or procedural interventions could improve outcomes. Clinical trial information: NCT03850912 . [Table: see text]
Efficacy-effectiveness gap with immune checkpoint inhibitors in solid cancers: A population based cohort study.
Authors: Niraula Saroj
Published: June 2023

6625

Background: Immune checkpoint inhibitors (ICIs) have been central in oncology drug development in the last decade often demonstrating large improvements in overall survival (OS) in pivotal randomized controlled trials (RCTs). Patient selection and/or care may be less stringent in the real world but ascertaining that benefits are translated satisfactorily from pivotal RCTs into the real world is crucial, as patients often base their treatment decisions on outcomes quoted to them from pivotal RCTs. Methods: After necessary ethics approvals, we collected relevant data on all consecutive patients with advanced solid cancers treated with ICIs in the province of Manitoba, Canada from inception to June 30, 2022 using pharmacy database and cancer registry. Eight most frequent ICI indications are included here. Survival probabilities were plotted using Kaplan-Meier Method, and descriptive statistics used to report relationship between variables. To put outcomes into perspective, we report real world data alongside that of pivotal RCTs used to support approvals of respective ICIs by Health Canada and the US FDA. Results: Eight ICI indications included 992 patients followed for a median of 40 months (range: 21-86 months). Patients required to meet precise provincial formulary criteria to receive ICIs, adopted mostly from the inclusion criteria of the corresponding pivotal RCTs. Median OS was shorter in the real world population not only compared to the experimental arms of the respective pivotal RCTs [by a median of 16 months (range: 3 - 38 months)] but also compared to their control arms [by a median of 3 months (range 3 to 32 months)]. This translated into an average of 51.1% (standard deviation: 20.1) compromise in median OS with ICIs in the real world compared to that observed in respective pivotal RCTs. Conclusions: Treatment with ICIs within high standards of practice in a Canadian province overall offered less than half the median OS observed in pivotal RCTs supporting their approvals. Current ICI treatment decisions by patients (and physicians) may therefore be based on highly inaccurate expectations. Our results should inspire rigorous phase IV clinical studies to identify pertinent real-world variables affecting outcomes including treatment related morbidity and mortality, with an ultimate aim to narrow the alarming efficacy-effectiveness gap. [Table: see text]