Understanding health outcome preferences of older adults diagnosed with multiple myeloma.

INTRODUCTION: Health outcome preferences of older adults with cancer vary based on burden/intensity of treatment and its impact on health outcomes such as survival, quality of life, and functional and cognitive well-being. We studied the association between age and health outcome preferences of adults with multiple myeloma (MM). MATERIALS AND METHODS: Using a single center prospective cohort study, we identified adults ≥50y with MM who underwent geriatric assessment (GA) within 30 days of initiating a new line of therapy. We assessed health outcome preferences using a nine-item health outcome preference scale where patients were asked to prioritize varying treatment outcomes in a Likert scale. We compared the response patterns for each item by age group (50-69y vs ≥70y) using Mantel-Haenszel chi-squared test. For items significant in bi-variable analysis, we built proportional odds models to study the association between age and health outcome preferences adjusting for sex, race, frailty, and high risk cytogenetics. RESULTS: We included 119 patients with a median age of 65y. Of these, 58% were male, 56% were non-Hispanic White, and 28% were frail. Older adults (≥70y) versus younger adults (50-69y) were more likely to prioritize health outcomes such as quality of life (53% vs. 34%), functional independence (74% vs. 33%), maintaining cognitive ability (79% vs. 54%), and living free from pain (50% vs 18%) over longer survival (all p values <0.05). In multivariable models, each one interquartile range (IQR) increase in age was associated with increased odds of prioritization of functional independence [adjusted odds ratio (aOR) 2.55, 95% confidence interval (CI) (1.44-4.53)], maintaining cognitive ability [aOR 1.75, 95% CI (1.01-3.02)], and willingness to take milder/ fewer treatments [aOR 2.40, 95% CI (1.36-4.26)] over longer survival. Similarly, each IQR increase in age was associated with decreased odds of prioritization of survival over quality of life [aOR 0.45, 95% CI (0.26-0.78)] and survival over being free from pain [aOR 0.39, 95% CI (0.22-0.69)]. DISCUSSION: Three out of four older adults (age ≥ 70y) with MM rated other outcomes, particularly functional and cognitive well-being, above survival. Determining the most significant treatment outcomes for older adults with MM can aid in establishing treatment goals and enhance shared decision-making.

A rare case of tumor-to-tumor metastasis of esophageal adenocarcinoma into meningioma.

Tumor-to-tumor metastasis is a known but rare occurrence and is characterized as 2 distinct tumor types in same anatomic location. We present a rare case of intracranial tumor-to-tumor metastasis of esophageal adenocarcinoma into meningioma. Our case emphasizes the rare occurrence of intracranial tumor-to-tumor metastasis and importance of histology and immunohistochemical analysis in distinguishing between metastasis and meningioma, especially when faced with ambiguous demarcation. Awareness of this occurrence is crucial, given that metastases might be the initial indication of an underlying tumor and it can impact the clinical management decisions.

Charting the Course: Insights into Neuroendocrine Tumor Dynamics in the United States.

OBJECTIVE: To explore changing trends and characteristics in neuroendocrine tumors (NETs) epidemiology, focusing on demographics, clinical aspects, and survival, including the impact of social determinants of health (SDOH) on outcomes. BACKGROUND: The escalating incidence and prevalence of NETs underscore the pressing need for updated epidemiologic data to reveal the evolving landscape of this condition. Access to current information is imperative for informing clinical strategies and public health initiatives targeting NETs. METHODS: A retrospective, population-based study analyzed NET patient data from 1975 to 2020, using the Surveillance, Epidemiology, and End Results (SEER 8, 12, 18) program. We calculated annual age-adjusted incidence, prevalence, and 5-year overall survival (OS) rates. Survival trends from 2000 to 2019 were examined, employing the Fine-Gray model to evaluate cancer-specific mortality. RESULTS: NETs' age-adjusted incidence rate quadrupled from 1.5 per 100,000 in 1975 to 6.0 per 100,000 in 2020. A decline in incidence occurred from 6.8 per 100,000 in 2019 to 6.0 per 100,000 in 2020. All-cause survival multivariable analysis demonstrated high grade (HR: 2.95, 95% CI: 2.63-3.09, P<0.001), single patients (HR: 1.49, 95% CI: 1.45-1.54, P<0.001), and Black patients (HR: 1.17, 95% CI:1.13-1.22, P<0.001) all had worse survival than their controls. CONCLUSION: In conclusion, our study shows a steady increase in NETs incidence until 2019, with a decline in 2020. Understanding the reasons behind this trend is vital for improved management and public health planning. Further research should focus on the factors driving these changes to enhance our understanding of NET epidemiology.

Clonal Hematopoiesis and Therapy-Related Myeloid Neoplasms After Autologous Transplant for Hodgkin Lymphoma.

PURPOSE: Therapy-related myeloid neoplasm (t-MN) is a life-threatening complication of autologous peripheral blood stem cell transplantation (aPBSCT) for Hodgkin lymphoma (HL). Although previous studies have reported an association between clonal hematopoiesis (CH) in the infused PBSC product and subsequent post-aPBSCT risk of t-MN in patients with non-HL, information about patients with HL treated with aPBSCT is not available. METHODS: We constructed a retrospective cohort of 321 patients with HL transplanted at a median age of 34 years (range, 18-71). Targeted DNA sequencing of PBSC products performed for CH-associated or myeloid malignancy-associated genes identified pathogenic mutations in these patients. RESULTS: CH was identified in the PBSC product of 46 patients (14.3%) with most prominent representation of DNMT3A (n = 25), PPM1D (n = 7), TET2 (n = 7), and TP53 (n = 5) mutations. Presence of CH in the PBSC product was an independent predictor of t-MN (adjusted hazard ratio [aHR], 4.50 [95% CI, 1.54 to 13.19]). Notably all patients with TP53 mutations in the PBSC product developed t-MN, whereas none of the patients with DNMT3A mutations alone (without co-occurring TP53 or PPM1D mutations) did. Presence of TP53 and/or PPM1D mutations was associated with a 7.29-fold higher hazard of t-MN when compared with individuals carrying no CH mutations (95% CI, 1.72 to 30.94). The presence of TP53 and/or PPM1D mutations was also associated with a 4.17-fold higher hazard of nonrelapse mortality (95% CI, 1.25 to 13.87). There was no association between CH and relapse-related mortality. CONCLUSION: The presence of TP53 and/or PPM1D mutations in the PBSC product increases the risk of post-aPBSCT t-MN and nonrelapse mortality among patients with HL and may support alternative therapeutic strategies.

Biomarkers of bleeding and venous thromboembolism in patients with acute leukemia.

BACKGROUND: Coagulopathy and associated bleeding and deep vein thrombosis (DVT) are major causes of morbidity and mortality in patients with acute leukemia. The underlying mechanisms of these complications have not been fully elucidated. OBJECTIVES: To evaluate the associations between biomarker levels and bleeding and DVT in acute leukemia patients. METHODS: We examined plasma levels of activators, inhibitors, and biomarkers of the coagulation and fibrinolytic pathways in patients aged ≥18 years with newly diagnosed acute leukemia compared with those of normal controls. Multivariable regression models were used to examine the association of biomarkers with bleeding and DVT in acute leukemia patients. The study included 358 patients with acute leukemia (29 with acute promyelocytic leukemia [APL], 253 with non-APL acute myeloid leukemia, and 76 with acute lymphoblastic leukemia) and 30 normal controls. RESULTS: Patients with acute leukemia had higher levels of extracellular vesicle tissue factor (EVTF) activity, phosphatidylserine-positive extracellular vesicles, plasminogen activator inhibitor-1, plasmin-antiplasmin complexes, and cell-free DNA and lower levels of citrullinated histone H3-DNA complexes compared with normal controls. APL patients had the highest levels of EVTF activity and the lowest levels of tissue plasminogen activator among acute leukemia patients. There were 41 bleeding and 23 DVT events in acute leukemia patients. High EVTF activity was associated with increased risk of bleeding (subdistribution hazard ratio, 2.30; 95% CI, 0.99-5.31), whereas high levels of plasminogen activator inhibitor-1 were associated with increased risk of DVT (subdistribution hazard ratio, 3.00; 95% CI, 0.95-9.47) in these patients. CONCLUSION: Our study shows alterations in several biomarkers in acute leukemia and identifies biomarkers associated with risk of bleeding and DVT.

Adolescents and young adults (AYA) with cancer: the clinical course of COVID-19 infections.

Adolescents and Young Adults (AYAs: 15-39 y) with cancer face unique vulnerabilities, yet remain under-represented on clinical trials, including adult registries of COVID-19 in cancer (AYAs: 8-12%). Thus, we leveraged the Pediatric Oncology COVID-19 Case Report (POCC) to examine the clinical course of COVID-19 among AYAs with cancer. POCC collects de-identified clinical and sociodemographic data regarding 0-39yo with cancer (AYAs = 37%) and COVID-19 from >100 institutions. Between 04/01/2020-11/28/2023, 191 older AYAs [22-39y] and 640 younger AYAs [15-21y] were captured. Older AYAs were less often hospitalized (p < .001), admitted to the intensive care unit (ICU, p = .02), and/or required respiratory support (p = .057). In multivariable analyses, older AYAs faced 80% lower odds of ICU admission but 2.3-times greater odds of changes to cancer-directed therapy. Unvaccinated patients had 5.4-times higher odds of ICU admission. Among AYAs with cancer, the COVID-19 course varies by age. These findings can inform pediatric/adult oncology teams surrounding COVID-19 management and prevention.

Body composition and late-occurring chronic health conditions after autologous stem cell transplantation for lymphoma.

BACKGROUND: Autologous peripheral blood stem cell transplantation (aPBSCT) is the standard of care for adults with relapsed lymphoma, yet recipients remain at risk of developing chronic health conditions (CHCs). It was hypothesized that body composition measurements of skeletal muscle and fat are associated with late-onset CHCs and nonrelapse mortality after aPBSCT. METHODS: Leveraging the Blood or Marrow Transplant Survivor Study, we examined association between pre-aPBSCT body composition and new-onset grade 3-5 CHCs among 187 adults with lymphoma treated with aPBSCT (2011-2014) surviving ≥2 years after aPBSCT. Using computed tomography scans at the L3 level, skeletal muscle mass (skeletal muscle area and skeletal muscle density [SMD]) and body fat (subcutaneous adipose tissue and visceral adipose tissue) were measured and quantified as sex-specific z-scores. Competing risk models were built to study the impact of body composition on incident grade 3 through 5 CHCs and nonrelapse mortality (NRM) adjusting for confounders. RESULTS: The study cohort had a median age at aPBSCT of 57 years with 63% males, 77% non-Hispanic Whites and 81% with non-Hodgkin lymphoma. The 5-year cumulative incidence of grade 3 through 5 CHCs was 47% (95% Confidence Interval, CI, 38%-56%). Each SD increase in SMD was associated with 30% reduced risk of grade 3 through 5 CHCs (95% CI, 0.50-0.96). The 10-year cumulative incidence of NRM was 16% (95% CI, 10-22). No body composition measure was associated with NRM. CONCLUSIONS: The association between SMD and grade 3 through 5 CHCs following aPBSCT could inform development of prognostic models to identify adults with lymphoma at greatest risk of morbidity following aPBSCT.

Low skeletal muscle mass and treatment outcomes among adults with haematologic malignancies: A systematic review and meta-analysis.

BACKGROUND: Low skeletal muscle mass (LSMM) and/or, function associated with an increased risk of treatment-related toxicities and inferior overall survival (OS) among adults with solid malignancies. However, the association between LSMM and treatment-related toxicities among adults with haematologic malignancies remains unclear. METHODS: Using a pre-published protocol (CRD42020197814), we searched seven bibliographic databases from inception to 08/2021 for studies reporting the impact of LSMM among adults ≥18 years with a known haematologic malignancy. The primary outcome of interest was OS, and secondary outcomes included progression free survival (PFS) and non-relapse mortality (NRM). These effect sizes were quantified in terms of hazards ratio (HR) along with 95% confidence interval (CI) and pooled across studies using a DerSimonian-Laird random-effects model. Heterogeneity was assessed using the Cochran's Q and the I2 statistic. All hypothesis testing was two-sided with an alpha of 0.05. RESULTS: Of 3791 studies screened, we identified 20 studies involving 3468 patients with a mean age of 60 years; 44% were female and the most common malignancy was diffuse large B-cell lymphoma (42%). Most studies measured muscle mass using single slice computed tomography imaging at the L3 level. The presence of LSMM was associated with worse OS (pooled HR = 1.81, 95% CI = 1.48-2.22, P < 0.001) with moderate heterogeneity (Cochran's Q, I2 = 60.4%), PFS (pooled HR = 1.61, 95% CI = 1.28-2.02, P < 0.001) with moderate heterogeneity (Cochran's Q, I2 = 66.0%). Similarly, LSMM was associated with worse NRM (HR = 1.72, 95% CI = 1.34-2.22, P < 0.001) with little evidence of heterogeneity (Cochran's Q, I2 = 0.0%). CONCLUSIONS: LSMM is associated with worse survival outcomes among adults with haematologic malignancies. Further research into understanding the underlying mechanism of this association and mitigating the negative effects of LSMM among adults with haematologic malignancies is needed.

Estimating the Impact of Rurality in Disparities in Cancer Mortality.

PURPOSE: Estimation of the independent effect of rurality on cancer mortality requires causal inference methodology and consideration of area-level socioeconomic status and rural designations. METHODS: Using SEER data, we identified key incident cancers diagnosed between 2000 and 2016 at age ≥20 years (N = 3,788,273), examining a 20% random sample (n = 757,655). Standardized competing risk and survival models estimated the association between rural residence, defined by Rural-Urban Continuum Codes, and cancer-specific and all-cause mortality, controlling for age at cancer diagnosis, sex, race/ethnicity, year of diagnosis, and Area Deprivation Index (ADI). We estimated the attributable fraction (AF) of rurality and high ADI (ADI > median) to the probability of mortality. Finally, we examined county measurement issues contributing to mortality rates discordant from hypothesized rates. RESULTS: The 5-year standardized failure probability for cancer mortality for rural patients was 33.9% versus 31.56% for urban. The AF for rural residence was 1.04% at year 1 (0.89% by year 5), the highest among local stage disease (Y1 2.1% to Y5 1.9%). The AF for high ADI was 3.33% in Y1 (2.87% in Y5), while the joint effect of rural residence and high ADI was 4.28% in Y1 (3.71% in Y5). Twenty-two percent of urban counties and 30% of rural were discordant. Among discordant urban counties, 30% were only considered urban because of adjacency to metro area. High ADI was associated with urban discordance and low ADI with rural discordance. CONCLUSION: Rural residence independently contributes to cancer mortality. The rural impact is the greatest among those with localized disease and in high deprivation areas. Rural-urban county designations may mask high-need urban counties, limiting eligibility to state and federal resources dedicated to rural areas.

Pre-frailty after blood or marrow transplantation and the risk of subsequent mortality.

We examined the prevalence, risk factors, and association between pre-frailty and subsequent mortality after blood or marrow transplantation (BMT). Study participants were drawn from the BMT Survivor Study (BMTSS) and included 3346 individuals who underwent BMT between 1974 and 2014 at one of three transplant centers and survived ≥2 years post-BMT. Participants completed the BMTSS survey at a median of 9 years from BMT and were followed for subsequent mortality for a median of 5 years after survey completion. Closest-age and same-sex biological siblings also completed the survey. Previously published self-reported indices (exhaustion, weakness, low energy expenditure, slowness, unintentional weight loss) classified participants as non-frail (0-1 indices) or pre-frail (2 indices). National Death Index was used to determine vital status and cause of death. Overall, 626 (18.7%) BMT survivors were pre-frail. BMT survivors had a 3.2-fold higher odds of being pre-frail (95% CI = 1.9-5.3) compared to siblings. Compared to non-frail survivors, pre-frail survivors had higher hazards of all-cause mortality (adjusted hazard ratio [aHR] = 1.6, 95% CI = 1.4-2.0). Female sex, pre-BMT radiation, smoking, lack of exercise, anxiety, and severe/life-threatening chronic health conditions were associated with pre-frailty. The novel association between pre-frailty and subsequent mortality provides evidence for interventions as pre-frail individuals may transition back to their robust state.

Trans-Ancestral Genetic Risk Factors for Treatment-Related Type 2 Diabetes Mellitus in Survivors of Childhood Cancer.

PURPOSE: Type 2 diabetes mellitus (T2D) is a prevalent long-term complication of treatment in survivors of childhood cancer, with marked racial/ethnic differences in burden. In this study, we investigated trans-ancestral genetic risks for treatment-related T2D. PATIENTS AND METHODS: Leveraging whole-genome sequencing data from the St Jude Lifetime Cohort (N = 3,676, 304 clinically ascertained cases), we conducted ancestry-specific genome-wide association studies among survivors of African and European genetic ancestry (AFR and EUR, respectively) followed by trans-ancestry meta-analysis. Trans-/within-ancestry replication including data from the Childhood Cancer Survivor Study (N = 5,965) was required for prioritization. Three external general population T2D polygenic risk scores (PRSs) were assessed, including multiancestry PRSs. Treatment risk effect modification was evaluated for prioritized loci. RESULTS: Four novel T2D risk loci showing trans-/within-ancestry replication evidence were identified, with three loci achieving genome-wide significance (P < 5 × 10-8). Among these, common variants at 5p15.2 (LINC02112), 2p25.3 (MYT1L), and 19p12 (ZNF492) showed evidence of modifying alkylating agent-related T2D risk in both ancestral groups, but showed disproportionately greater risk in AFR survivors (AFR odds ratios [ORs], 3.95-17.81; EUR ORs, 2.37-3.32). In survivor-specific RNA-sequencing data (N = 207), the 19p12 locus variant was associated with greater ZNF492 expression dysregulation after exposures to alkylators. Elevated T2D risks across ancestry groups were only observed with increasing values for multiancestry T2D PRSs and were especially increased among survivors treated with alkylators (top v bottom quintiles: ORAFR, 20.18; P = .023; OREUR, 13.44; P = 1.3 × 10-9). CONCLUSION: Our findings suggest therapy-related genetic risks contribute to the increased T2D burden among non-Hispanic Black childhood cancer survivors. Additional study of how therapy-related genetic susceptibility contributes to this disparity is needed.

Defining the Denominator for Measuring Quality of End-of-Life Care in Children with Cancer: Results of a Nominal Group Technique.

OBJECTIVE: To determine which groups of children with cancer for whom to apply the newly developed quality measures (QMs) for end-of-life (EOL) care. STUDY DESIGN: In a series of nominal groups, panelists answered the question: "Which children, diagnoses, conditions, or prognoses should be included when examining the quality of EOL care for children with cancer?" In each group, individual panelists proposed answers to the question. After collating individual responses, each panelist ranked their 5 top answers and points were assigned (5 pts for the best answer, 4 pts the second best, etc.). A team of pediatric oncology and palliative care clinician-scientists developed and applied a coding structure for responses and associated themes and subthemes for responses. RESULTS: We conducted 5 nominal groups with a total of 44 participants. Most participants identified as female (88%) and non-Hispanic White (86%). Seventy-nine percent were clinicians, mainly in pediatric palliative care, pediatric oncology, or hospice; 40% were researchers and 12% were bereaved parents. Responses fell into 5 themes: (1) poor prognosis cancer; (2) specific treatment scenarios; (3) certain populations; (4) certain symptoms; and (5) specific utilization scenarios. Poor prognosis cancer and specific treatment scenarios received the most points (320 pts [49%] and 147 pts [23%], respectively). CONCLUSIONS: Participants developed a framework to identify which children should be included in EOL QMs for children with cancer. The deliberate identification of the denominator for pediatric QMs serves as a potent tool for enhancing quality, conducting research, and developing clinical programs.

Late morbidity and mortality after autologous blood or marrow transplantation for lymphoma in children, adolescents and young adults-a BMTSS report.

We determined the risk of late morbidity and mortality after autologous blood or marrow transplantation (BMT) for lymphoma performed before age 40. The cohort included autologous BMT recipients who had survived ≥2 years after transplantation (N = 583 [HL = 59.9%; NHL = 40.1%]) and a comparison cohort (N = 1070). Participants self-reported sociodemographics and chronic health conditions. A severity score (grade 3 [severe], 4 [life threatening] or 5 [fatal]) was assigned to the conditions using CTCAE v5.0. Logistic regression estimated the odds of grade 3-4 conditions in survivors vs. comparison subjects. Proportional subdistribution hazards models identified predictors of grade 3-5 conditions among BMT recipients. Median age at BMT was 30.0 years (range: 2.0-40.0) and median follow-up was 9.8 years (2.0-32.1). Survivors were at a 3-fold higher adjusted odds for grade 3-4 conditions (95% CI = 2.3-4.1) vs. comparison subjects. Factors associated with grade 3-5 conditions among BMT recipients included age at BMT (>30 years: adjusted hazard ratio [aHR] = 2.31; 95% CI = 1.27-4.19; reference: ≤21 years), pre-BMT radiation (aHR = 1.52; 95% CI = 1.13-2.03; reference: non-irradiated), and year of BMT (≥2000: aHR = 0.54; 95% CI = 0.34-0.85; reference: <1990). The 25 years cumulative incidence of relapse-related and non-relapse-related mortality was 18.2% and 25.9%, respectively. The high risk for late morbidity and mortality after autologous BMT for lymphoma performed at age <40 calls for long-term anticipatory risk-based follow-up.

Contribution of County Characteristics to Disparities in Rural Mortality After Cancer Diagnosis.

INTRODUCTION: Rural disparities in cancer outcomes have been widely evaluated, but limited evidence is available to describe what characteristics of rural environments contribute to the increased risk of poor outcomes. Therefore, this manuscript sought to assess the mediating effects of county characteristics on the relationship between urban/rural status and mortality among patients with cancer, characterize county profiles, and determine at-risk county profiles alongside rural settings. METHODS: Patients diagnosed with cancer between 2000 and 2016 were assessed using Surveillance, Epidemiology and End Results data linked to the 2010 Rural-Urban Commuting Codes and 2010 County Health Rankings. There were 757,655 patients representing 596 counties (of 3,143 in the U.S.) and 12 states. Mediation analyses, conducted in 2023, estimated the direct contribution of rurality to 5-year all-cause survival and the contribution of the rural effect indirectly through County Health Ranking domains. Latent class analysis and survival models identified county groupings and estimated the hazard of mortality associated with class membership. RESULTS: Rankings for premature death, clinical care, and physical environment resulted in rural patients having 17.9%-20.2% less survival time than urban patients. Of this, 4.1%-12.6% of the total excess risk was mediated by these characteristics. Patients living in rural and high-risk county classes saw higher all-cause mortality than those in urban lower-risk counties (hazard ratio=1.04, 95% CI=1.01, 1.08 and 1.07, 95% CI=1.03, 1.11). CONCLUSIONS: Counties with poorer health rankings had increased mortality risks regardless of rurality; however, the poor rankings, notably health behaviors and social and economic factors, elevated the risk for rural counties.

Deficiencies in germline genetic testing in young-onset colorectal cancer patients.

BACKGROUND: Young-onset colorectal cancer (YO-CRC) patients have high rates of pathologic genetic variants on germline testing, however it is unclear what factors are associated with genetic testing completion. METHODS: We performed a retrospective review of YO-CRC patients aged ≤50 years between 2014 and 2021 who received the entirety of their cancer care at a single institution. The primary outcome was completion of germline multigene panel testing. Variables were examined for association with germline multigene panel testing. RESULTS: Among 100 YO-CRC patients, only 31 â€‹% (n â€‹= â€‹31) completed genetic testing. Testing rates did not differ by colorectal cancer stage but were significantly higher among patients who received chemotherapy (39.8 â€‹% vs 5.9 â€‹%; p â€‹= â€‹0.01) and in patients with increasing number of relatives with a family history of cancer (p â€‹< â€‹0.01). CONCLUSIONS: Only one-third of YO-CRC patients completed genetic testing. Patients seen by oncology or with increasingly strong family cancer history were more likely to complete genetic testing.

Time Kills: Impact of Socioeconomic Deprivation on Timely Access to Guideline-Concordant Treatment in Foregut Cancer.

BACKGROUND: Receipt of guideline-concordant treatment (GCT) is associated with improved prognosis in foregut cancers. Studies show that patients living in areas of high neighborhood deprivation have worse healthcare outcomes; however, its effect on GCT in foregut cancers has not been evaluated. We studied the impact of the area deprivation index (ADI) as a barrier to GCT. STUDY DESIGN: A single-institution retrospective review of 498 foregut cancer patients (gastric, pancreatic, and hepatobiliary adenocarcinoma) from 2018 to 2022 was performed. GCT was defined based on National Comprehensive Cancer Network guidelines. ADI, a validated measure of neighborhood disadvantage was divided into terciles (low, medium, and high) with high ADI indicating the most disadvantage. RESULTS: Of 498 patients, 328 (66%) received GCT: 66%, 72%, and 59% in pancreatic, gastric, and hepatobiliary cancers, respectively. Median (interquartile range) time from symptoms to workup was 6 (3 to 13) weeks, from diagnosis to oncology appointment was 4 (1 to 10) weeks, and from oncology appointment to treatment was 4 (2 to 10) weeks. Forty-six percent were diagnosed in the emergency department. On multivariable analyses, age 75 years or older (odds ratio [OR] 0.39 [95% CI 0.18 to 0.87]), Black race (OR 0.52 [95% CI 0.31 to 0.86]), high ADI (OR 0.25 (95% CI 0.14 to 0.48]), 6 weeks or more from symptoms to workup (OR 0.44 [95% CI 0.27 to 0.73]), 4 weeks or more from diagnosis to oncology appointment (OR 0.76 [95% CI 0.46 to 0.93]), and 4 weeks or more from oncology appointment to treatment (OR 0.63 [95% CI 0.36 to 0.98]) were independently associated with nonreceipt of GCT. CONCLUSIONS: Residence in an area of high deprivation predicts nonreceipt of GCT. This is due to multiple individual- and system-level barriers. Identifying these barriers and developing effective interventions, including community outreach and collaboration, leveraging telehealth, and increasing oncologic expertise in underserved areas, may improve access to GCT.

Effect of carvedilol versus placebo on cardiac function in anthracycline-exposed survivors of childhood cancer (PREVENT-HF): a randomised, controlled, phase 2b trial.

BACKGROUND: Carvedilol improves cardiac function in patients with heart failure but remains untested as cardioprotective therapy in long-term childhood cancer survivors (ie, those who have completed treatment for childhood cancer and are in remission) at risk for heart failure due to high-dose anthracycline exposure. We aimed to evaluate the activity and safety of low-dose carvedilol for heart failure risk reduction in childhood cancer survivors at highest risk for heart failure. METHODS: PREVENT-HF was a randomised, double-blind, phase 2b trial done at 30 hospitals in the USA and Canada. Patients were eligible if they had any cancer diagnosis that resulted in at least 250 mg/m2 cumulative exposure to anthracycline by age 21 years; completed their cancer treatment at least 2 years previously; an ejection fraction of at least 50% or fractional shortening of at least 25%, or both; and bodyweight of at least 40 kg. Patients were randomly assigned (1:1) with automated computer-generated permuted block randomisation (block size of 4), stratified by age at diagnosis, time since diagnosis, and history of chest-directed radiotherapy, to carvedilol (up-titrated from 3·125 g per day to 12·5 mg per day) or placebo orally for 2 years. Participants, staff, and investigators were masked to study group allocation. The primary endpoint was to establish the effect of carvedilol on standardised left ventricular wall thickness-dimension ratio Z score (LVWT/Dz). Treatment effects were analysed with a linear mixed-effects model for normally distributed data with a linear time effect and testing the significance of treatment*time interaction in the modified intention-to-treat (mITT) cohort (ie, all randomly assigned participants who had a baseline and at least one subsequent echocardiogram measurement). Safety was assessed in the ITT population (ie, all randomly assigned participants). This trial was registered with ClinicalTrials.gov, NCT027175073, and enrolment and follow-up are complete. FINDINGS: Between July 3, 2012, and June 22, 2020, 196 participants were enrolled, of whom 182 (93%) were eligible and randomly assigned to either carvedilol (n=89) or placebo (n=93; ITT population). Median age was 24·7 years (IQR 19·6-36·6), 91 (50%) participants were female, 91 (50%) were male, and 119 (65%) were non-Hispanic White. As of data cutoff (June 10, 2022), median follow-up was 725 days (IQR 378-730). 151 (n=75 in the carvedilol group and n=76 in the placebo group) of 182 participants were included in the mITT population, among whom LVWT/Dz was similar between the two groups (-0·14 [95% CI -0·43 to 0·16] in the carvedilol group vs -0·45 [-0·77 to -0·13] in the placebo group; difference 0·31 [95% CI -0·10 to 0·73]; p=0·14). Two (2%) of 89 patients in the carvedilol group two adverse events of grade 2 or higher (n=1 shortness of breath and n=1 arthralgia) and none in the placebo group. There were no adverse events of grade 3 or higher and no deaths. INTERPRETATION: Low-dose carvedilol appears to be safe in long-term childhood cancer survivors at risk for heart failure, but did not result in significant improvement of LVWT/Dz compared with placebo. These results do not support the use of carvedilol for secondary heart failure prevention in anthracycline-exposed childhood cancer survivors. FUNDING: National Cancer Institute, Leukemia & Lymphoma Society, St Baldrick's Foundation, Altschul Foundation, Rally Foundation, American Lebanese Syrian Associated Charities.