tbuckley/cabot-search huggingface dataset:
Approaches to engaging participants in a national cancer genomics research network.
Authors: Norah L. Crossnohere, Anne L.R. Schuster, Shiraz I Mishra, Bethany Kwan
Journal: Journal of Clinical Oncology (2024)

11022 Background: Although patient engagement is thought to improve the relevance and acceptability of research across diverse patient populations, a paucity of studies actively evaluate engagement activities to assess their impact. The NCI’s Participant Engagement and Cancer Genome Sequencing (PE-CGS) Network was established to advance cancer genomics for understudied cancers and among underserved populations by engaging patients and survivors as participants in research. We sought to characterize strategies for engaging and evaluating engagement among research centers within PE-CGS, and to describe factors impacting each center’s unique engagement strategies and evaluation methods. Methods: We used a multi-method approach to document centers’ engagement strategies and methods to evaluate engagement.We first completed a document review of centers’ study materials including protocols, specific aims, and publicly available information. We then conducted semi-structured key informant interviews with research center members to validate findings from the document review and to identify factors that influenced engagement strategies. The semi-structured interview guide was developed using the Health Equity Implementation Framework to ensure that we accounted for multi-level factors (societal, contextual, and clinical factors) relevant to engagement. Engagement strategies and evaluation methods were collated and analyzed descriptively. Information about factors that influenced their engagement strategies were analyzed using deductive thematic analysis. Results: Across the five PE-CGS research centers, we identified 9 engagement strategies including: convening at network meetings (n=5), use of advisory boards (n=5), brochures (n=3), newsletters (n=2), community outreach through advocacy organizations (n=1) and in-person events (n=2), and use of branded websites (n=4), social media (n=3), and health technology apps (n=1). Methods used for evaluating engagement included: surveys (n=4), interviews/focus groups (n=4), informal feedback from participants (n=2), randomized experiments (n=1), and N-of-1 studies (n=1). Multi-level factors that influenced engagement included those related to the language and culture of the patient population, availability of validated measures, timing of interactions with participants within their health journey, and patient burden imposed by the experienced cancer. Conclusions: Across a national research network with a priority to advance participant engagement in cancer genomics research, we observed a range of unique engagement strategies and evaluation methods. Notably evaluation approaches were not typically tied to specific engagement strategies, but rather sought to evaluate broader aspects of engagement in the respective research studies, such as their ability to engender inclusivity, collaboration, and trust among participants.
Prescription drug monitoring program mandates and opioid prescriptions received by patients dying of cancer.
Authors: Yuhua Bao, Hao Zhang, Laura C Pinheiro, Allison Ju-Chen Hu, Russell K. Portenoy, Eduardo Bruera, M. Carrington Reid, Rulla M. Tamimi, Fang Zhang, Judith A. Paice, William E. Rosa
Journal: Journal of Clinical Oncology (2024)

11003 Background: Strong consensus supports opioid analgesics as first-line pain management for patients with poor prognosis cancer approaching the end of life (EoL). State legislations that mandate prescriber access of Prescription Drug Monitoring Programs (PDMPs) when prescribing opioids intend to mitigate unsafe opioid prescriptions but may have unintended consequences in restricting access to opioids for patients dying from cancer. This study seeks to assess associations between state implementation of comprehensive PDMP mandates –applicable to all prescribers and all clinical settings and not allowing prescriber discretion – with opioid prescriptions received by patients dying of cancer. Methods: We used SEER cancer registry linked with Medicare fee-for-service claims to identify 184,123 Medicare beneficiaries 66 years or older who died of cancer in 2011-2019 in one of 10 SEER states with an operating PDMP by the beginning of 2011. We measured opioid prescriptions dispensed to patients near the EoL, defined as 30 days prior to death or hospice admission. We exploited staggered implementation of comprehensive PDMP mandates and assessed the association of such implementation with opioid prescriptions dispensed to patients near the EoL. We estimated logistic regressions for dichotomous outcomes and Generalized Linear Models for continuous outcomes. Results: Implementation of comprehensive PDMP mandates was associated with a reduction in the rate of 1 or more opioid days near the EoL from 47.2% to 45.2% (difference, 0.02 [95% CI, -0.027, -0.012]), a reduction in the rate of 1 or more long-acting opioid days from 15.8% to 14.7% (difference, 0.011 [95% CI, -0.016, -0.006]), and a reduction of 130.8 (95% CI, -161.5, -100.2) in total morphine milligram equivalents (MMEs) and of 135.6 (95% CI, -215.1, -56.1) in MMEs from long-acting opioids among patients who received 1 or more days of opioids/long-acting opioids. Conclusions: Comprehensive PDMP mandates were associated with 4-9% reduction in opioid prescriptions dispensed to patients at the EOL. Specific strategies are needed to effectively exempt patients with active cancer from such mandates. [Table: see text]
The effect of advances in management of uterine-serous-carcinoma on population mortality.
Authors: Aifen Wang, Shunyu Hou, Ninghan Feng, Weidong Hu, Yayun Zhang, Jiaqi Xu
Journal: Journal of Clinical Oncology (2024)

e22516 Background: Incidence and mortality of uterine cancer has reported to be declining. However, mortality trends of endometrial serous carcinoma remain unclear at a population level. Methods: We applied SEER to evaluate uterine-serous- carcinoma mortality and relevant deaths of this disease to incident cases. We assessed trends of population mortality based on specific causes and races. Incidence of uterine serous carcinoma were evaluated based on ethics and calendar year. Trends of incidence and incidence-based mortality were evaluated by Joinpoint software. Results: Incidence of uterine serous carcinoma decreased by 1.51% from 2000 through 2017, followed by increase of 16.58% from 2017 through 2019. Mortality of women with uterine serous carcinoma due to uterine serous carcinoma decreased by 4.33% annually from 2000 to 2010, and then decreased at a rate of 1.88% every year from 2010 to 2017, and then sharply declined by 44.69% from 2017 to 2019. Mortality of women with uterine serous carcinoma due to other causes increased by 0.94% annually from 2000 to 2016, and then increased at a high rate of 35.18% every year from 2016 to 2019. Incidence-based mortality of women with uterine serous carcinoma due to other causes increased by 39.03% annually from 2000 to 2004, and then increased at a rate of 2.93% every year from 2004 to 2019. Incidence-based mortality of patients due to other causes showed similar pattern. Patients’ incidence-based mortality due to uterine serous cancer increased at rates of 111.02% and 9.80% annually from 2000 through 2002, from 2002 through 2006 respectively, followed by a decrease of 3.87% annually from 2006 through 2019, and then a gradual increase of 6.55% annually from 2002 through 2005. Incidence of white patients with uterine serous cancer decreased at a rate of 4.42% from 2000 through 2017 and then increased by 21.61% from 2017 through 2019. Incidence of Asians patients presented similar pattern. However, incidence of Black patients increased at a rate of 0.93% from 2000 through 2015 and then sharply increased by 8.49%. Incidence-based mortality of white patients with uterine serous cancer increased at a rate of 105.16% from 2000 through 2002, and then increased by 10.93% from 2002 through 2006, followed by a decrease of 3.40% from 2006 through 2019. Incidence-based mortality of Black patients elevated at a rate of 114.03% from 2000 through 2002, and flatten out, increased by 1.94% from 2002 through 2019. Incidence-based mortality of Asian patients showed similar pattern. Conclusions: Declined incidence-based mortality from 2006 through 2019 may associate with management advances of uterine serous carcinoma. Decreased incidence-based mortality of White patients with uterine serous carcinoma from 2006 through 2019 and increased incidence-based mortality of Black patients and Asian patients with uterine serous carcinoma in same period may related to better management resource of White patients.
Associations between prognosis and primary endpoint selection in phase III oncology trials in the United States.
Authors: Nariaki Uemura, Shunsuke Ono
Journal: Journal of Clinical Oncology (2024)

e23022 Background: Overall survival (OS) is commonly used as a primary endpoint in phase III oncology trials in the United States, serving as direct evidence of clinical benefit and as an objective outcome measure. Other endpoints such as progression-free survival (PFS) and objective response rate (ORR) are also utilized. Factors such as a cancer type and treatment line are considered important for primary endpoint selection, however, the fundamental factor influencing primary endpoint selection across various cancer types or treatment lines remains unclear. I hypothesize that the prognosis of the target patient population is one of the key fundamental factors across any groups in primary endpoint selection. This study aims to investigate the associations between the prognosis and the type of primary endpoint. Methods: All phase 3 clinical trials conducted in the US, focusing on drug therapies for cancer, between January 1, 2015 and Dec 31, 2022 were included. Multinomial logistic regression was utilized to assess the relationships between prognosis, indicated by the median overall survival of the control arm, and the type primary endpoint among OS, non-OS time-to-event endpoints (Other TTE), and response or remission rate (RR). Models were adjusted for cancer type, treatment line, the primary endpoint of the previous clinical study for the same target patient population, monotherapy, mechanism of action (MOA), biomarker for the drug, orphan drug designation (ODD), and accelerated approval (AA) before regulatory approval. Results: Out of 5,877 phase 3 clinical trials, 151 studies and 167 evaluation sets were included in the analysis. When the prognosis and the type of primary endpoint were tested, this factor demonstrated a statistically significant difference with a positive coefficient for Other TTE, RR, and a co-primary endpoint of OS and Other TTE compared to OS. The prognosis, the median OS of the control arm, was 10.5 months (95% CI 5.00-16.6) for OS, 18.5 months (95% CI 7.50-34.3) for Other TTE, 32.9 months for RR, and 13.6 months (95% CI 8.7-46.6) for the co-primary endpoint of OS and Other TTE respectively. No effect modification was observed for Other TTE and the co-primary endpoint of OS and Other TTE. Conclusions: A better prognosis is associated with the selection of surrogate endpoints in phase 3 oncology trials among many factors. The associations between the prognosis and the type of primary endpoint were observed for Other TTE and a co-primary endpoint of OS and Other TTE. These findings elucidate one of the fundamental factors for primary endpoint selection and emphasize the importance of prognosis in selecting a primary endpoint in phase 3 clinical trial in oncology in the US. However, further study is required to comprehensively understand the impact of RR on primary endpoint selection, as this analysis was limited by the lack of median OS data for RR.
Baseline surveillance in Li Fraumeni syndrome using whole-body MRI: A systematic review and meta-analysis.
Authors: Maria Inez Dacoregio, Pedro Cotta Abrahão Reis, Davi Said Gonçalves Celso, Lorena Escalante Romero, Stephan Altmayer, Maysa Vilbert, Fabio Ynoe de Moraes, Israel Gomy
Journal: Journal of Clinical Oncology (2024)

e22555 Background: Li-Fraumeni syndrome (LFS) is a cancer syndrome associated with early-onset neoplasias. Risk management through a routine cancer surveillance strategy is critical. Since patients with LFS are susceptible to radiation-induced cancers, the use of whole-body MRI (WBMRI) is recommended for regular cancer screening. However, the guidelines for clinical management and the evidence supporting the benefits of WBMRI surveillance in asymptomatic LFS patients are limited. Therefore, this systematic review and meta-analysis assessed the clinical utility of WBMRI in germline TP53 mutation carriers at baseline and at follow up. Methods: We systematically searched Pubmed, Cochrane, and Embase libraries for studies evaluating WBMRI as an early detection method for tumor screening in patients with LFS. We pooled the prevalence and presented the overall rate with 95% confidence intervals (CI) of the individuals found to have one or more investigable lesions, the lesions found to be new cancers among suspicious lesions, and the individuals with one or more new cancers among the total population. Statistical analysis was performed using R software version 4.3.1 and heterogeneity was evaluated with I2 statistics. Results: From 1,547 initial studies, 11 (10 observational cohort and 1 case control) comprising 703 patients (359 females [51%]; mean [SD] age, 29.5 [+/-25] years) were included from 7 different countries. Median follow-up of lesions ranged from 2 to 11 years. We found an estimated detection rate of 31% (95% CI 28-34, I2 55%) of any suspicious lesions in asymptomatic TP53 carriers who underwent baseline WBMRI was found. In total, 277 lesions that required clinical follow-up in 215 patients were identified. Cancer was confirmed in 46 lesions in 39 individuals. Most of the cancers found were Central Nervous System (CNS) tumors (n = 16), followed by sarcomas (n = 12) and breast cancer (n = 11). The estimated cancer diagnosis rate among suspicious lesions was 18% (95%CI 13-25, I2 5%). WBMRI detected 41 of 46 cancers in the early disease stage, with an overall detection rate of 6% (95% CI 5-8, I2 47%). Incidence rate was 2% per patient-round of WBMRI (95% CI 1-4, I2 0%), including baseline plus follow up. Conclusions: Our systematic review and meta-analysis supports that surveillance with WBMRI is effective in detecting cancers in patients with LFS. Additionally, WBMRI surveillance was successful in diagnosing almost 90% of cancers in early-disease stage, which increases the chances os cure in this young population.
Correlation of cost in teaching hospital with outcomes in patients with cardiac myxoma: A retrospective study using the national in-patient data sample (NIS).
Authors: Volha Chapiolkina, Esmirna Perez, Nehemias Antonio Guevara-Rodriguez, Manoj Ghimire, Kalpana Ghimire, Coral Olazagasti
Journal: Journal of Clinical Oncology (2024)

e23062 Background: Cardiac myxoma (CM) is a rare cancer, benign but functionally malignant. It is the most common cardiac tumor and is more frequent in females in North America and Europe. Mortality has been associated with cardiac burden complications and the resolving capacity of the medical center to diagnose and treat these complications. Methods: A retrospective cohort analysis focused on adults admitted to hospitals between 2016 and 2020 with a primary diagnosis of CM. Data for this study were obtained from the NIS Database. The primary outcome was to determine if higher cost in teaching hospitals has an impact on mortality outcomes compared with non-teaching teaching hospitals. We looked at sociodemographic characteristics, length of stay (LoS), and complications as secondary outcomes. Hypothesis testing for categorical variables was tested with Chi-Square. Continuous variables were tested with a Student t-test. Statistical significance was defined as a two-tailed P value of &lt; 0.05. Results: A total of 3,744 patients met inclusion criteria: 3014 were within teaching hospitals (TH), and 730 were within no-teaching hospitals (NTH). The median age was similar in both settings: 64 years in TH and 68 years in NTH (p &lt; 0.001). LoS was higher in TH, 7.6 days, vs. NTH, 6.3 days (p = 0.05). Hospitalization costs were higher in TH, for a mean of $156,658 than in NTH, for a mean of $109,328 (p &lt; 0.001). Most patients were females, 1850 in TH and 405 in NTH (p = 0.24). Mortality was higher in TH 75 vs. NTH 45 (p = 0.02). The population was composed of mostly White patients (68% in TH vs. 73% in NTH), followed by Back (14% in TH vs. 9% in NTH), Hispanics (11% in TH vs. 9% in NTH), Asian (3% in TH vs. 6% in NTH) and Native American patients (5% in TH vs. 0% in NTH) (p = 0.22). Patients were located mainly in the south region (39% in TH vs. 43% in NTH), followed by a similar distribution between the West (20% in TH vs. 27% in NTH), Central (23% in TH vs. 20% in NTH) and East regions (20% in TH vs. 10% in NTH) (p = 0.02). The most frequent payer was Medicare, 56% in TH vs 64% in NTH and private insurance, 28% in TH vs 24% in NTH (p &lt; 0.001). Cardiac pathologies were the most frequent comorbidities: Congestive Heart Failure (p = 0.39), Cardiovascular disease (p = 0.18), hypertension (p = 0.1), and coronary artery disease (p = 0.44). The most common complications were cardiovascular, as demonstrated in previous studies. Conclusions: Cardiac Myxoma is a benign tumor with fatal severe complications that affect the more elderly female white population. Our study revealed a lack of significance between the outcome and the type of hospital in which patients received treatment. Similarly, mortality was not found to be driven by sociodemographic characteristics in our analysis.
Overestimation of survival in individuals with cancer treated in the real world with new cancer drugs: A population-based cohort study.
Authors: Saroj Niraula
Journal: Journal of Clinical Oncology (2024)

e23076 Background: Oncologists and individuals with cancer often rely on outcomes from pivotal randomized controlled trials (RCTs) for real-world treatment decisions. However, stringent inclusions and standardized protocols limit their applicability. This study quantifies overall survival (OS) disparities for novel cancer drugs between real-world and pivotal RCTs. Methods: Ethics approvals were secured, and data on frequently used targeted cancer drugs for solid cancer treatment in all individuals with cancer in Manitoba, Canada from inception to June 30, 2023, collected using pharmacy database and the Manitoba Cancer Registry. Evidence consistently indicates similar cancer outcomes in Manitoba to most high-resource countries. This analysis includes six common immunotherapies and monoclonal antibodies. Kaplan-Meier Method was used to plot survival probabilities, and descriptive statistics to elucidate variable differences. Comparison between survival outcomes in pivotal RCTs and real-world scenarios was expressed as "Overestimation Quotient or OQ" (OS in RCT over OS in the real world for same indication). Results: A total of 941 individuals diagnosed with cancer were evaluated across eight indications. The observed median OS in the real world for included indications was 11.9 months, ranging from 6.6 to 37.6 months— a duration significantly shorter than the median OS reported in pivotal Randomized Controlled Trials (RCTs) (31.35 months, range 9.2 to 72.1) (P &lt; 0.001). This translated to a median difference of 15.6 months (range 2.6 to 59.9) per indication and an "Overestimation Quotient" ranging from 1.5 to 5.9. Notably, the observed OS was even inferior in the real-world setting compared to the control group used in pivotal RCTs in half of the indications (Table 1). Conclusions: In routine practice, new cancer drugs offer starkly inferior survival compared to that reported in pivotal RCTs used for approval of those drugs, with the difference in survival ranging from a few months to several years, translating up to six-fold difference. Our results highlight potential for alarming misinformation influencing treatment decisions in clinics. We trust that oncologists will consider our findings during treatment discussions in clinics. [Table: see text]
NSQIP audit of enhanced recovery after surgery protocols for radical cystectomy.
Authors: John Pfail, Rachel Passarelli, Alain Kaldany, Kevin J. Chua, Benjamin Lichtbroun, Arnav Srivastava, David Golombos, Thomas L Jang, Vignesh T. Packiam, Saum Ghodoussipour
Journal: Journal of Clinical Oncology (2024)

11009 Background: Utilization of enhanced recovery after surgery (ERAS) protocols for radical cystectomy (RC) has been associated with improved postoperative recovery and shorter hospital stays. The multiple components within ERAS leads itself to heterogenous implementation across different institutions. We aimed to assess the impact of increasing compliance to ERAS components on postoperative outcomes in patients who underwent RC. Methods: The National Surgical Quality Improvement Program database included 3,708 patients who underwent RC from 2019 to 2021. ERAS components of interest included regional anesthesia block, no bowel prep, no prolonged NGT or NPO status, VTE prophylaxis with mechanical and pharmacologic means, and antibiotic duration &lt; 24 hours. Baseline characteristics and complications were stratified by number of ERAS components utilized (≤ 3, 4, or 5). Statistical endpoints included thirty-day complications, length of stay (LOS), and readmissions. Optimal RC outcome was defined as absence of any postoperative complication, reoperation, prolonged LOS (75th percentile, 8 days) with no readmission. Multivariable analyses with Bonferroni correction were performed to assess the association between ERAS compliance and outcomes. Results: Of the 3,708 patients who underwent RC with ERAS components utilized, 1,506 (41%) received ≤ 3 interventions, 1454 (39%) received 4, and 748 (20%) received 5. Baseline characteristics were relatively similar across the three groups. On multivariable analysis adjusted for multiple hypothesis testing, when compared to patients who received ≤ 3 interventions, patients who received 4 and 5 interventions had lower rates of any complication (OR 0.71; 99% CI [0.58 - 0.88], OR 0.74 [0.57 - 0.95], respectively), and shorter LOS (β -1.32 [-1.69, -0.95], β -1.74 [-2.19, -1.28], respectively). Moreover, patients with increased ERAS compliance experienced increased odds of an optimal outcome (OR 1.68 [1.38 – 2.05], OR 1.97 [1.55 – 2.51], respectively). Conclusions: Greater adherence to ERAS protocol interventions yielded superior post-operative outcomes for patients who underwent RC. This large-scale analysis supports that ERAS protocols are beneficial in a dose-dependent fashion and should be utilized. [Table: see text]