Large Cancer Center Research Articles

Favorable Survival after Definitive Ablative RT in Surgically Resectable Pancreatic Cancer Patients

Surgical resection has been considered the only curative option for patients with pancreatic adenocarcinoma (PDAC). Ablative RT ≥100Gy BED10 (A-RT) is associated with favorable survival in patients with locally advanced unresectable disease. We sought to evaluate A-RT outcomes in patients with technically resectable disease who did not undergo surgery. Our prospectively maintained database of patients treated with A-RT was queried for consecutive patients with radiographic T1/T2 resectable PDAC. Patients were treated with a standardized technique within a large academic cancer center regional network. Ablative RT using several hypofractionated regimens was delivered on either standard Linacs with respiratory motion management, CBCT image guidance and selective adaptive replanning or MR-Linac with compression belt and daily on-line adaptive replanning. Freedom from local progression (FFLP), distant metastasis-free and overall survival (DMFS and OS, respectively) were analyzed using the Kaplan Meier estimates. Between 2016 and 2022, 28 patients (54% male) with radiographically resectable PDAC received definitive A-RT. Median age was 80 (interquartile range, 77-84) years and 23 (82.1%) had KPS of 80 or below. Eighteen patients (64.3%) had T2 cancer, 5 (17.9%) were node positive, and 23 (82.1%) had head location. Median size was 2.6 (range, 1.6-4.0) cm with a median carbohydrate antigen 19-9 (CA19-9) of 160.5 (0-1823) U/mL. Twenty patients (71.4%) received induction chemotherapy for a median of 2.4 (0-6.2) months. RT regimens delivered on conventional Linacs unless otherwise indicated included 75Gy in 25 fractions (n = 15), 67.5Gy in 15 fractions (n = 10), 50Gy in 5 (N = 2, MR Linac), 60Gy in 10 (n = 1). 24-month FFLP and DMFS were 78.8% (52.3-91.7%) and 17.7% (95% CI, 5.8%-34.8%), respectively. 24-month and 48-month rate of OS from A-RT were 49.1% (95% CI, 27.53-67.5%) and 36.3 (95%16.0-57.1%). Grade 3 acute and late GI toxicity was noted in 3 and 1 patients, respectively, including 2 bleeding events treated with transfusions. There were no ≥ grade 4 events. In patients with surgically resectable PDAC we found that definitive A-RT following multiagent induction therapy was associated with oncologic outcomes similar to resection with minimal toxicity.

Sexual Orientation and Gender Identity (SOGI) Data Collection: Opportunities to Advance Best Clinical Practices for LGBTQ+ Patients in Radiation Oncology

A long-standing barrier to progress against health disparities is the lack of data regarding cancer risks, prevalence, treatment, and outcomes for sexual and gender minority (SGM) patients. Sexual orientation and gender identity (SOGI) data are not routinely collected by individual oncologists, cancer centers, or most non-federal hospital systems. Alarmingly high proportions of SGM patients report discrimination in healthcare or avoid routine care due to perceived lack of acceptance in the healthcare system. For these and other reasons, healthcare institutions must adopt practices that promote an inclusive environment for all patients including those self-identified from SGM groups. One strategy to achieve this aim is through SOGI data collection. The purpose of this study was to pilot new procedures and training for SOGI data collection, the aims of this project were to standardize the collection of SOGI data for all new patients referred to the Division of Radiation Oncology; promote clinical staff awareness of SGM health disparities and strategies for fostering an inclusive hospital environment; and to provide SGM patients and caregivers educational resources and support systems tailored to their needs. We designed a Quality Improvement program for collecting SOGI data, which was approved by our institution's QIAB. Patient access specialists (PAS) were trained to collect SOGI data from newly registered patients and enter the data into the electronic health record. Radiation Oncology staff completed surveys before and after SOGI training to estimate its impact on the provision of patient care. A Fisher's exact test was utilized to evaluate associations between training and provider-reported outcomes. Within a 3-week period starting in January 2023, two 1-hour interactive training sessions were offered to twenty-five PAS. Three 1-hour training sessions were offered to twenty-seven Radiation Oncology clinical staff. (1) Confidence for incorporating SOGI classifiers around patients improved from before training (52%, 13/25) to after training (100%, 17/17) among medical providers surveyed (odds ratio (OR) 32, 95% confidence interval (CI) 0.70-1493, p = 0.005). Use of SOGI data in clinical decision making increased from before training (9/25, 36%) to after training (100%, 17/17) among medical providers (OR 60.79, 95% CI 3.271-1130, p<0.0001). (2) A clinical pathway for SGM patients was developed to facilitate referral to our institution's SGM patient support group and distribution of patient education materials focused on sexual health. Establishing standardized SOGI data collection can facilitate the provision of tailored resources and care that meets the needs of patients and staff in a large comprehensive cancer center. Specialized training for staff developed through this initiative helps foster an inclusive and welcoming environment that promotes the integration, visibility, and advancement of SGM cancer care at our institution.

Radiation Oncology Practice Changes during the COVID-19 Pandemic

The purpose of this study was to characterize the effects of institutional policies routine SARS-CoV-2 testing before treatment starts with mandatory quarantine periods for COVID-positive patients during the first year of the COVID19 pandemic across radiation oncology sections at our tertiary cancer center. Electronic medical databases were queried to identify all patients treated with curative intent at a large urban cancer center and regional satellites a year prior to the pandemic (02/11/19-12/30/19; pre-pandemic) and the first year of the pandemic (03/11/20-12/30/20; post-pandemic). New treatment starts were filtered for those undergoing treatment under a single ICD-10 diagnosis and the first treatment in each time period for each patient. Chi-square tests were used for categorical variables, and the t-test was used for continuous variables to correlate differences in demographic and clinical factors before and during the pandemic. The total number of new treatment starts were similar between the pre-pandemic (2,218 patients) and post-pandemic (2,130 patients) periods, but there was a 26% decrease in treatments in April 2020 compared to April 2019 and a 40% increase in treatments in November 2020 compared to November 2019. Post-pandemic patients had higher minimum Charlson Comorbidity Index scores (mean 46.0 vs 42.6, P = 0.0013) and were younger (62.8 yo vs 64.3 yo, P = 0.0001). The proportion of patients being treated from the same state as our institution was higher in the post-pandemic period compared to pre-pandemic (77.8% vs 72.43%, P = 0.0259). Distribution of treatments across department disease-site sections were significantly different (P<0.0001), with the proportion of patients treated by the Breast service having increased by 22% whereas the metropolitan area regional satellites experienced a 18% reduction. There were no statistically significant differences amongst pre- and post-pandemic patients with respect to race, marital status, or smoking status. Post-pandemic patients had less total radiation-related clinical visits (mean 24.8 vs 28.6, P<0.0001), lower administered dose (4329 cGy vs 4533 cGy, P<0.0001), and lower radiation fraction count (17 vs 19, P<0.0001). There was no statistically significant difference in the duration between CT simulation and treatment start, but post-pandemic patients had shorter duration of elapsed days during treatment (27 days vs 29 days, P = 0.0001). A disease-site-specific analysis demonstrated that these differences were most pronounced in patients treated for breast cancer. In the first year of the COVID19 pandemic, our institution saw a dynamic change in the number of new radiation treatments. Additional analyses across individual disease-specific services may reveal insight into dose, fractionation, and technique, which may account for the observed differences.

Evaluation of factors predicting the benefit from systemic oncological treatment for severely ill hospitalized patients: a retrospective study

BackgroundPatients with cancer in the disease’s end-stage with poor performance represent a challenging clinical scenario, as they have high chance of a fatal outcome due to clinical conditions, oncological emergencies, and/or metastatic disease. This study examines the factors predicting the potential benefit of “urgent” chemotherapy during hospitalization in this setting, thus addressing a research gap.MethodsThis retrospective observational study was conducted in the largest cancer center in the outskirts of São Paulo. It identified factors predicting the benefit from antineoplastic treatment in severe in-hospital patients admitted during 2019–2020, considering post-chemotherapy survival time as the main dependent variable. Data were retrieved from medical records. All patients aged ≥ 18 years, with an ECOG-PS score ≥ 2, and undergoing non-elective systemic cancer treatment were included.ResultsThis study evaluated 204 records, of which 89 were included in the final analysis. A statistically significant association with the worse outcome (death within 30 days of chemotherapy) was found with higher ECOG performance status; chemotherapy dose reduction; lower values of serum albumin, hemoglobin, and creatinine clearance; and higher values of leukocytes, neutrophils, direct bilirubin, urea, and C-reactive protein. In the multivariate analysis, only albumin remained statistically associated with the outcome (hazard ratio = 0.35; confidence interval: 0.14, 0.90; p = 0.034).ConclusionsSerum albumin and other clinical and laboratory variables might be associated with early post-treatment deaths in patients with cancer. The study data might help guide the decision to administer systemic treatment in this scenario and manage critically ill patients. This study adds to our knowledge of the factors predicting the objective benefits from “heroic” or “urgent” chemotherapy for hospitalized and severely ill patients with cancer.

CDK4/6 inhibitors versus weekly paclitaxel for treatment of ER+/HER2- advanced breast cancer with impending or established visceral crisis

PurposeER+/HER2- advanced breast cancer (ABC) with visceral crisis (VC) or impending VC (IVC) is commonly treated with chemotherapy instead of CDK4/6 inhibitors (CDK4/6i). However, there is little evidence to confirm which treatment is superior. This study compared outcomes of patients with ER+/HER2- ABC and IVC/VC treated with CDK4/6i or weekly paclitaxel.MethodsPatients with ER+/HER2- ABC receiving first line treatment at a large tertiary UK cancer centre from 1-Mar-2017 to 30-Jun-2021 were retrospectively identified. Hospital records were screened for IVC/VC affecting the liver, lungs/mediastinum, gastrointestinal tract and/or bone marrow. Baseline demographics, clinical data and survival outcomes were recorded up to 30-Jul-2022.Results27/396 (6.8%) patients with ABC who received CDK4/6i and 32/86 (37.2%) who received paclitaxel had IVC/VC. Median time to treatment failure (TTF), progression-free survival (PFS) and overall survival (OS) were significantly longer in the CDK4/6i compared to paclitaxel cohort: TTF 17.3 vs. 3.5 months (HR 0.33, 95%CI 0.17–0.61, p = 0.0002), PFS 17.8 vs. 4.5 months (HR 0.38, 95%CI 0.21–0.67, p = 0.002), OS 24.6 vs. 6.7 months (HR 0.37, 95%CI 0.20–0.68, p = 0.002). The median time to first improvement in IVC/VC was similar in patients receiving CDK4/6i compared to paclitaxel (3.9 vs. 3.6 weeks, p = 0.773). Disease control at 4 months was not significantly different in the CDK4/6i and paclitaxel cohorts (77.8% vs. 59.4%, p = 0.168). In multivariate analysis, treatment with CDK4/6i was independently associated with a longer PFS compared to paclitaxel (HR 0.31, 95%CI 0.12–0.78, p = 0.015).ConclusionIn this retrospective study, patients with ER+/HER2- ABC and IVC/VC treated with CDK4/6i had a significantly better survival compared to those treated with weekly paclitaxel. Further prospective studies that minimise possible selection bias are recommended.

Socio-economic determinants for the place of last care: results from the acute palliative care unit of a large comprehensive cancer center in a high-income country in Europe

Background and introductionThe place of last care carries importance for patients at the end of life. It is influenced by the realities of the social welfare and healthcare systems, cultural aspects, and symptom burden. This study aims to investigate the place of care trajectories of patients admitted to an acute palliative care unit.Materials and methodsThe medical records of all patients hospitalized on our acute palliative care unit in 2019 were assessed. Demographic, socio-economic and disease characteristics were recorded. Descriptive and inferential statistics were used to identify determinants for place of last care.ResultsA total of 377 patients were included in this study. Median age was 71 (IQR, 59–81) years. Of these patients, 56% (n = 210) were male. The majority of patients was Swiss (80%; n = 300); about 60% (n = 226) reported a Christian confession; and 77% had completed high school or tertiary education. Most patients (80%, n = 300) had a cancer diagnosis. The acute palliative care unit was the place of last care for 54% of patients. Gender, nationality, religion, health insurance, and highest level of completed education were no predictors for place of last care, yet previous outpatient palliative care involvement decreased the odds of dying in a hospital (OR, 0.301; 95% CI, 0.180–0.505; p-value < 0.001).ConclusionMore than half of patients admitted for end-of-life care died on the acute palliative care unit. While socio-economic factors did not determine place of last care, previous involvement of outpatient palliative care is a lever to facilitate dying at home.

Consent document translation expense hinders inclusive clinical trial enrolment.

Patients from historically under-represented racial and ethnic groups are enrolled in cancer clinical trials at disproportionately low rates in the USA1-3. As these patients often have limited English proficiency4-7, we hypothesized that one barrier to their inclusion is the cost to investigators of translating consent documents. To test this hypothesis, we evaluated more than 12,000 consent events at a large cancer centre and assessed whether patients requiring translated consent documents would sign consent documents less frequently in studies lacking industry sponsorship (for which the principal investigator pays the translation costs) than for industry-sponsored studies (for which the translation costs are covered by the sponsor). Here we show that the proportion of consent events for patients with limited English proficiency in studies not sponsored by industry was approximately half of that seen in industry-sponsored studies. We also show that among those signing consent documents, the proportion of consent documents translated into the patient's primary language in studies without industry sponsorship was approximately half of that seen in industry-sponsored studies. The results suggest that the cost of consent document translation in trials not sponsored by industry could be a potentially modifiable barrier to the inclusion of patients with limited English proficiency.

A short screening tool identifying systemic barriers to distress screening in cancer care.

International guidelines on cancer treatment recommend screening for early detection and treatment of distress. However, screening rates are insufficient. In the present study, a survey was developed to assess perceived systemic barriers to distress screening. A three-step approach was used for the study. Based on qualitative content analysis of interviews and an expert panel, an initial survey with 53 questions on barriers to screening was designed. It was completed by 98 nurses in a large comprehensive cancer center in Switzerland. From this, a short version of the survey with 24 questions was derived using exploratory principal component analysis. This survey was completed by 150 nurses in four cancer centers in Switzerland. A confirmatory factor analysis was then performed on the shortened version, yielding a final set of 14 questions. The initial set of 53 questions was reduced to a set of 14 validated questions retaining 53% of the original variance. These 14 questions allow for an assessment within 2-3 min that identifies relevant barriers to distress screening from the perspective of those responsible for implementation of distress screening. Across several hospitals in Switzerland, the timing of the first distress screening, lack of capacity, patient and staff overload, and refusal of distressed patients to be referred to support services emerged as major problems. The validated 14 questions on barriers to screening cancer patients for distress enable clinicians and hospital administrators to quickly identify relevant issues and take action to improve screening programs.

Temporal dynamics of genetically heterogeneous extended-spectrum cephalosporin-resistant Escherichia coli bloodstream infections.

Extended-spectrum cephalosporin-resistant Escherichia coli (ESC-R-Ec) is an urgent public health threat with sequence type clonal complex 131 (STc131), phylogroup B2 strains being particularly concerning as the dominant cause of ESC-R-Ec infections. To address the paucity of recent ESC-R-Ec molecular epidemiology data in the United States, we used whole-genome sequencing (WGS) to fully characterize a large cohort of invasive ESC-R-Ec at a tertiary care cancer center in Houston, Texas, collected from 2016 to 2020. During the study time frame, there were 1,154 index E. coli bloodstream infections (BSIs) of which 389 (33.7%) were ESC-R-Ec. Using time series analyses, we identified a temporal dynamic of ESC-R-Ec distinct from ESC-susceptible E. coli (ESC-S-Ec), with cases peaking in the last 6 months of the calendar year. WGS of 297 ESC-R-Ec strains revealed that while STc131 strains accounted for ~45% of total BSIs, the proportion of STc131 strains remained stable across the study time frame with infection peaks driven by genetically heterogeneous ESC-R-Ec clonal complexes. bla CTX-M variants accounted for most β-lactamases conferring the ESC-R phenotype (89%; 220/248 index ESC-R-Ec), and amplification of bla CTX-M genes was widely detected in ESC-R-Ec strains, particularly in carbapenem non-susceptible, recurrent BSI strains. Bla CTX-M-55 was significantly enriched within phylogroup A strains, and we identified bla CTX-M-55 plasmid-to-chromosome transmission occurring across non-B2 strains. Our data provide important information regarding the current molecular epidemiology of invasive ESC-R-Ec infections at a large tertiary care cancer center and provide novel insights into the genetic basis of observed temporal variability for these clinically important pathogens. IMPORTANCE Given that E. coli is the leading cause of worldwide ESC-R Enterobacterales infections, we sought to assess the current molecular epidemiology of ESC-R-Ec using a WGS analysis of many BSIs over a 5-year period. We identified fluctuating temporal dynamics of ESC-R-Ec infections, which have also recently been identified in other geographical regions such as Israel. Our WGS data allowed us to visualize the stable nature of STc131 over the study period and demonstrate a limited but genetically diverse group of ESC-R-Ec clonal complexes are detected during infection peaks. Additionally, we provide a widespread assessment of β-lactamase gene copy number in ESC-R-Ec infections and delineate mechanisms by which such amplifications are achieved in a diverse array of ESC-R-Ec strains. These data suggest that serious ESC-R-Ec infections are driven by a diverse array of strains in our cohort and impacted by environmental factors suggesting that community-based monitoring could inform novel preventative measures.

Mortality during or shortly after Curative-Intent Radio-(Chemo-)Therapy over the last decade at a large comprehensive cancer center.

Definitive surgical, oncological and radio-oncological treatment may result in significant morbidity and acute mortality. Mortality during or shortly after treatment in patients undergoing curative radio-(chemo)-therapy has not been studied systematically. We reviewed all curative radio-(chemo-)therapies at a large comprehensive cancer center over the last decade. The institutional record was screened for patients who received curative-intent radio-(chemo-)therapy and deceased during or within 30days after radiotherapy. Curative therapy was defined as prescribed dosage of EQD2≥50Gy for radiotherapy alone and EQD2≥40Gy for radiochemotherapies. Data on demographics, disease and treatment were assembled and assessed. Of 15,255 radiotherapy courses delivered at our center, 8,515 (56%) were performed with curative-intent. During or within 30days after radio-(chemo-)therapy, 78 patients died (0.9% of all curative-intent courses). Median age of the deceased patients was 70 (IQR, 62-78) years, and 36% (28/78) were female. Median pre-therapeutic ECOG-PS was 1 (IQR, 0-2) and Charlson-Comorbidity-Index was 3+ (IQR, 2-3+). The most common primary malignancies were head and neck cancer (33/78; 42%) and central nervous system tumors (13/78; 17%). Peritherapeutic mortality varied by primary tumor, with the highest prevalence observed in head and neck and gastrointestinal cancer patients with 2.9% (33/1,144) and 2.4% (8/332), respectively. Among patients with known cause of death (34/78; 44%), tumor progression (12/34; 35%) and pulmonary complications/causes (11/34; 35%) were most common. On multivariable regression analysis, a worse ECOG-PS was associated with a relatively earlier peri-radiotherapeutic death (p=0.014). Mortality during or within 30days of curative-intent radio-(chemo-)therapy was low, yet highest for head and neck (2.9%) and gastrointestinal tumor (2.4%) patients. Reasons for these findings include rapid tumor progression in some cancers, good patient selection, with ECOG-PS being most useful and predictive for avoiding early mortality. Future research should help refine predictors for peri-RT mortality.

Resuscitation outcomes in patients with cancer: experience in a large urban cancer centre.

Hospitalized patients with cancer who experience cardiopulmonary arrest have historically low survival rates. This retrospective cohort study describes outcomes of patients at a large Canadian cancer centre who had a "code medical emergency" activated, and the use of pragmatic criteria to identify patients with poor survival following resuscitation. We included hospitalized patients with cancer who had a "code blue" activated between January 2007 and December 2018. Our primary outcome was intensive care unit (ICU) mortality. We developed pragmatic criteria to identify patients with "poor prognosis" for survival from cardiopulmonary resuscitation (CPR) based on disease status and candidacy for further cancer treatment. We used descriptive statistics to analyze the outcomes of poor prognosis patients. Two hundred and twenty-five patients had a code blue activated. The median age was 61 yr, 52% were male, and 48% had a solid tumour. Overall, 173/225 (77%) patients survived the code blue; 164 were admitted to the ICU, where 49% (81/164) died; 31% survived to hospital discharge; and 16% (n=27) were alive at one year. One hundred and twenty out of 225 (53%) required chest compressions; spontaneous circulation returned in 61% (73/120), and 12% (14/120) survived to hospital discharge. Patients meeting "poor prognosis" criteria (114, 51%) were more likely to die in the ICU (64% vs 35%; P<0.001) or in hospital (86% vs 59%; P<0.001), and more often had goals-of-care discussions prior to the code blue (46% vs 7%; P<0.001). At one year, only 2% of poor prognosis patients were alive, compared with 24% of patients who did not meet any poor prognosis criteria. Hospitalized patients with cancer requiring CPR have poor hospital and long-term outcomes. The proposed set of pragmatic criteria may be useful to identify patients unlikely to benefit from CPR and life support, to trigger early goals of care discussions, and to avoid potentially goal-discordant interventions.

Ocular Toxicity Profile of Targeted Cancer Therapy (TCT) at a US Tertiary Cancer Center.

Targeted cancer therapy (TCT) is a significant advancement in oncology with promising survival improvement in patients with cancer and remarkable effects on various cancers. There is evidence suggesting a connection between specific TCT classes and the occurrence of immune-related adverse events (irAEs). Our study aims to investigate the potential ocular toxicities of different classes of TCT, provide a better understanding of these toxicities, and aid in the future development of screening and management recommendations for ocular irAEs. Retrospective observational case series. Only ocular immune-related AEs were included in the study; patients on TCT who received a new ophthalmic diagnosis were seen atthe MD Anderson Cancer Center. Between 2010 and 2019, we retrospectively reviewed the medical records of 6,354 patients on TCT at a large US tertiary cancer center. Results:The criteria for data analysis were met by 1861 patients. TCT was associated with a wide range of class-specific ocular irAEs. There was a statistically significant correlation between ocular toxicity with polytherapy with a p-value of <0.001. Furthermore, there was a statistically significant correlation between toxicity and BRAF, epidermal growth factor receptor (EGFR), and ICI <0.001, <0.001, and 0.006, respectively. Conclusion:Our cohort is the most extensive case series in English literature, demonstrating the increased risk of class-specific ocular toxicity associated with TCT, which sheds some light on the importance of developing standardized grading criteria and management guidelines.

Clinicians’ experiences with patients with cancer or their families who endorse medical misinformation.

11042 Background: Medical misinformation causes delays in cancer care, forgoing of treatment, economic harms, potentially toxic effects, and harmful medical interactions with standard curative treatments. Previous literature has examined patients’ traits and beliefs. However, effectively caring for patients with cancer who endorse medical misinformation also requires better understanding the experiences, competencies, and concerns of the clinicians who treat them. We conducted an IRB approved study of physicians and advanced practice providers at a large cancer center. Methods: We surveyed clinicians about following themes: i) prevalence of misinformation, ii) attitudes towards patients endorsing misinformation, iii) strategies and competence, iv) resources to help them successfully address patients. Results: 87 clinicians responded to the survey. The median response was 15% of patients endorse claims that are false or misleading about standard-of-care cancer treatments and 20% endorse claims that overstate the benefits or understate the risks of unconventional treatments. The most common misinformation concerned herbs and supplements. Clinicians ranked provides hope and poor medical literacy as the top reasons for why their patients endorse medical misinformation followed by distrust in conventional medicine, cultural factors, and religiosity. The primary attitude clinicians project to patients when they request unconventional treatments was Openness/Equanimity (75.6%), Curiosity (43.9%), Skepticism (18.3%), Disdain/Disappointment (0, 0.0%), Other (6.1%). The primary internal attitude clinicians experienced in these situations was Openness/Equanimity (25.6%), Skepticism (57.3%), Curiosity (40.2%), Disdain/Disappointment (22.0%), Other (6, 7.3%). When asked if they’d be open to a patient using a harmless unconventional treatment that had no evidence of therapeutic benefit, 17.1% said yes, 17.1% said no, and 65.9% said it depends. Correcting misinformation is difficult: 38.2% report success rates below 60% for correcting misinformation and 68.5% report success rates below 80%. Several factors contributed to low success: Only 26% said that they have enough time to adequately address patients who endorse misinformation. Moreover, 46.9% report insufficient resources, 65% claim insufficient training, and 51.3% claim insufficient institutional support. Conclusions: Many cancer care providers feel insufficiently trained and supported to address patients who endorse medical misinformation. Cancer care institutions must develop training and resources to help clinicians effectively address patients who endorse misinformation about their care.

Association of remote, longitudinal patient-reported outcomes (PROs) and step counts with hospitalization or death among patients with advanced cancer undergoing chemotherapy: Secondary analysis of the PROStep randomized trial.

1581 Background: Patients with advanced cancer undergoing chemotherapy experience significant symptoms and declines in functional status, which are often associated with poor outcomes. Remote monitoring of PROs (symptoms) and step counts (functional status), may proactively identify patients at risk of hospitalization or death. Our objectives were to evaluate the association of 1) longitudinal PROs with step counts, and 2) PROs and step counts with hospitalization or death. Methods: The PROStep randomized trial (NCT04616768) enrolled 108 patients with advanced gastrointestinal (GI) or lung cancers undergoing cytotoxic chemotherapy at a large academic cancer center. Patients were randomized to weekly text-based monitoring of 8 PROs (each measured on a 0-4 scale) + continuous step count monitoring via Fitbit, vs usual care. This pre-planned secondary analysis included 57 of 75 patients randomized to the intervention who had PRO and step data. We analyzed associations between PROs and mean daily step count, and associations of PROs and step counts with the composite outcome of hospitalization or death, using bootstrapped generalized linear models to account for longitudinal data. Results: Among 57 evaluable patients, mean age was 57 years, 24 (42%) were female, 49 (86%) were White, 43 (75%) had advanced GI cancer, and 14 (25%) had advanced lung cancer. A 1-point weekly increase (on a 32-point scale) in aggregate PRO score was associated with 247 fewer mean daily steps (95% CI -277, -213, p &lt; 0.001). PROs most strongly associated with step count decline were patient-reported activity level (daily step change -892), nausea (-677), and constipation (-524). 25 patients (44%) were hospitalized (n = 21) or died (n = 8). A 1-point weekly increase in aggregate PRO score was associated with 20% greater odds of hospitalization or death (adjusted odds ratio [aOR] 1.2, 95% CI 1.1, 1.4, p = 0.008). PROs most strongly associated with hospitalization/death were pain (aOR 3.2), decreased activity (aOR 3.2), dypsnea (aOR 2.6) and sadness (aOR 2.1). A decrease in 1000 steps was associated with 16% greater odds of hospitalization or death (aOR 1.2, 95% CI 1.0, 1.3, p = 0.03). Compared to baseline, mean daily step count decreased 6.7%, 8.5%, 16.2% in the 3, 2, and 1 weeks prior to hospitalization/death. Mean aggregate PRO score increased by 11.0%, 25.3%, 36.4% in the 3, 2, and 1 weeks prior to hospitalization/death. Conclusions: In this secondary analysis of a randomized trial, increased PRO-based symptom burden was associated with lower daily step count. Higher symptom burden and decreased step count were independently associated with and predictably worsened close to hospitalization or death. Future interventions should leverage longitudinal PRO and step data to identify risk for poor outcomes. Clinical trial information: NCT04616768 .

Self-reported sleep difficulties and association with cognitive function in pediatric cancer survivors.

10065 Background: Preventing and ameliorating cognitive impairment following treatment for pediatric cancer remains a persistent challenge, with recent literature examining lifestyle factors as possible targets for intervention. An association between sleep and cognitive impairment has been identified in adult cancer patients and survivors, yet information is limited for pediatrics. Thus, the primary goal of our retrospective study was to explore self-reported sleep difficulties in pediatric patients and survivors with mixed cancers. A secondary aim was to explore the impact sleep problems on specific cognitive functions. Methods: Children and adolescents who completed neuropsychological assessments at two large pediatric cancer centers (N = 298) were identified via medical record review. In addition to demographic data, clinically collected cognitive tests included Wechsler Working Memory (WMI), Processing Speed (PSI), and General Ability (GAI) indices. Objective attention measures included Conners Continuous Performance Test (versions II and 3) Omissions (O), Commissions (C), and Reaction Time (RT). Sleep Disturbance (SD) and Sleep-Related Impairment (SRI) were captured using pediatric self-report PROMIS scales. PROMIS cut points were used to categorize sleep issues within the study population and PROMIS scores were compared to reference population means. Multiple linear regression was used to identify relationships between cognitive domains and sleep factors. Common cancer-related clinical and demographic characteristics were controlled as covariates. Results: 21.5% of patients reported severe SD, while 12.8%, 15.9% and 49.7% reported moderate, mild, and within normal limits (WNL) SD, respectively. For SRI, 13.3% reported severe SRI, while 20.0%, 15.9% and 50.8% reported moderate, mild and WNL SRI, respectively. Mean SD and SRI were higher than in the reference populations (p = 0.000 for both measures). Pearson correlation results suggested a moderate relationship between SD and SRI (r = 0.489, p = 0.000). After controlling for covariates, multiple linear regressions indicated significant relationships between SD and GAI (p = 0.006), SD and O (p = 0.018), and SRI and WM (p = 0.006). Conclusions: Results suggested that ~50% of our pediatric cancer patients and survivors reported SD and SRI. SD was correlated with SRI in our sample, and regression analysis indicates a significant relationship between sleep problems and O, WM, and GAI in our sample. Findings from this retrospective study suggest a relationship between sleep problems and cognitive performance in pediatric cancer survivors. As a potentially modifiable factor to improve cognitive function in pediatric cancer survivors, sleep difficulties warrant more research to potentially guide interventions to better manage and improve cognitive function in this population.

Identifying clinical trial candidates using AI predictions of treatment change: A pilot implementation study.

1515 Background: Precision oncology clinical trials often struggle to accrue due to the difficulty of identifying patients whose tumors meet complex tumor genomic matching criteria at propitious moments when they need new treatment. We conducted a pilot of deploying an artificial-intelligence (AI) model to find such patients and facilitate clinical trial matching workflows at a large academic cancer center. Methods: An AI model was trained to predict initiation of new palliative intent systemic therapy within 30 days of a given imaging report (CT, MRI, bone scan, or PET-CT), using the text of that report and prior reports for each patient. The model architecture and performance were previously published (Kehl et al, JCO-CCI 2021 5:622-630). From April to December 2022, the model was applied prospectively each time patients with solid tumors that had undergone next-generation sequencing underwent an imaging study. Model output was linked to the MatchMiner tool, which matches patients to clinical trials using tumor genomics (Klein et al, NPJ Precis Oncol 2022 6(1):69). The output consisted of lists of patients with tumor genomic matches to specific trials, sorted in order of the likelihood of changing treatment within 30 days. This information was provided to an oncology nurse navigator (ONN) charged with coordinating recruitment to early-phase targeted and immunotherapy trials. For 9 high priority trials, the ONN reviewed records for each patient flagged as likely to change treatment and contacted treating oncologists when patients appeared potentially eligible. The proportions of records leading to oncologist contact, and reasons for oncologist non-contact, were analyzed. Results: 2093 patients had tumors with genomic matches to the 9 trials of interest; 492 patients (24%) were deemed “likely” to change treatment by our AI model at least once during the pilot. The treating oncologist for 66 patients (3% of the total; 13% of 492 “likely” patients) was contacted after ONN review for potential eligibility. Reasons for not contacting treating oncologists included cases where they had already decided to continue current treatment (21%); the trial had no slots at the time (14%); or the patient was ineligible on nurse navigator review (12%); or had already been evaluated for the trial (7%), started new treatment (18%), or enrolled in hospice (5%). Of the 66 patients whose oncologists were contacted, 9 patients had a consult regarding early phase trials; 4 consented to participate; and all 4 received protocol treatment. Conclusions: Identifying potential precision clinical trial candidates by using AI to find patients likely to change treatment is feasible, but many other factors also impact potential trial enrollment. A prospective study is planned to evaluate the impact of sharing clinical trial information directly with treating oncologists when our model predicts a high probability of treatment change.

Malnutrition risk at diagnosis and influence on survival in patients with solid tumors at a large academic cancer center.

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 = &lt; 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 = &lt; 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]

Incidence of immune checkpoint inhibitor induced myocarditis in patients with mesothelioma from a regional tertiary cancer centre covering a patient population of 2.6 million.

e20541 Background: As a large regional tertiary cancer centre with an established cardio-oncology service a high incidence immune checkpoint inhibitor (ICI) induced myocarditis was recognised in mesothelioma patients receiving combination ICIs (cICI). A retrospective analysis of myocarditis in patients with mesothelioma was conducted. The utility of baseline cardiac markers as a prospective stratification tool for the development of ICI induced myocarditis in this patient group was investigated. Methods: A retrospective analysis of 118 patients with mesothelioma treated with ICIs over a 5 year period at the Clatterbridge Cancer Centre, Liverpool, UK. Baseline characteristics, treatment regimen, co-morbidities and the presence of malignant pericardial or cardiac disease were recorded. Baseline cardiac markers (high sensitivity Troponin T (hsTT) and pro-BNP) were recorded for patients initiating ICI treatment from July 2022 when regional baseline testing was introduced. A diagnosis of myocarditis was confirmed by cardiac MRI (n = 6) or clinically by the cardio-oncology team when MRI was clinically unfeasible (n = 1). Statistical analysis was undertaken with Fishers Exact test. Results: 33 patients received cICI treatment with Ipilimumab and Nivolumab, 85 patients received monotherapy ICIs (mICI), 5 as a SACT combination. Myocarditis occurred in 12.1% (n = 4) of patients receiving cICIs vs 3.5% (n = 3) of patients receiving mICIs. The median onset was 57 days with cICI and 245 days with mICI treatment. Baseline (b/l) cardiac assessment was undertaken in 22 patients (66.7%) of those treated with cICIs and 8 patients (9.4%) treated with mICI therapy. An abnormal b/l pro-BNP ( &gt; 500 ng/L) was identified in 5 cICI patients and 1 mICI patient. Those with elevated b/l pro-BNP in the cICI setting all had a significant cardiac association; either an increased incidence of myocarditis (n = 3/5) (p = 0.0065) or pericardial/ invasive cardiac disease (n = 2/5) (p = 0.0433). In the cICI population myocarditis was not seen in patients with a b/l pro-BNP &lt; 500ng/L. Of the 8 mICI patients with b/l cardiac assessment, 1 patient had an elevated pro-BNP which was associated with pericardial extension. Regarding baseline hsTT in the cICI group, the incidence of myocarditis was not increased with mild b/l elevations (14-24 ng/L), however, a moderately elevated level ( &gt; 24ng/L) was associated with an increased incidence of myocarditis (p = 0.0026). Conclusions: In this cohort of patients with mesothelioma there was a high incidence of cICI induced myocarditis. As patients treated with cICIs with abnormal b/l cardiac markers had an increased risk of developing ICI induced myocarditis, b/l cardiac markers could potentially be used to help stratify the risk of ICI induced myocarditis and inform treatment discussions. Further studies are now required.

Molecular landscape and survival outcomes on early phase clinical trials in sporadic young onset colorectal cancer.

3600 Background: Sporadic young onset colorectal cancer (YOCRC, ages 30-49) is a public health crisis with a persistent rise in incidence globally. While a proportion of patients (pts) develop YOCRC due to hereditary predisposition, the majority develop sporadic microsatellite stable (MSS) colorectal cancer with limited options beyond standard of care in advanced settings. We report the early phase clinical trial experience at a large academic cancer center to elucidate clues regarding molecular landscape and impact of clinical trials in refractory MSS YOCRC. Methods: Patient and clinical characteristics were summarized using descriptive statistics. Kaplan-Meier method was used to estimate the probabilities of overall survival (OS) and progression free survival (PFS). Log-rank tests were used to assess the differences in OS and PFS between subgroups. Cox proportional hazards regression models were fit to assess the association between OS or PFS and patient characteristics. Statistical analyses were performed using SAS and Splus. Results: 240 MSS YOCRC pts were analyzed. Median age 42.8 (20.5-49), &gt; 80% were white and only 10% black. 21% received at least 3 lines of therapy. The top five mutations were TP53, KRAS, APC, PI3CKA and BRAFV600E. Median OS was 39.2 months (95% CI: 34.8 – 42.5 months). CTNNB1 mutation was associated with a lower risk of death (HR = 0.28, 95% CI: 0.09 – 0.87, p-value = 0.03) while BRAFV600E mutation was associated with an increased risk (HR = 3.28, 95% CI: 2.00 – 5.38, p-value &lt; 0.001). Multivariable Cox model for OS revealed both CTNNB1 and BRAFV600E mutations are significant prognostic factors for OS, unlike KRAS. There was no difference in OS or PFS among pts who entered a mutation specific clinical trial vs. those enrolled on an unmatched clinical trial (p = 0.35, p = 0.68, respectively, log-rank test). Median PFS was 1.9 months (95% CI: 1.8 – 2.1 months). CTNNB1 mutation was associated with a lower risk of progression/death (HR = 0.29, 95% CI: 0.09 – 0.92, p-value = 0.04) while NRAS mutation was associated with an increased risk (HR = 2.13, 95% CI:1.19– 3.80, p-value = 0.01). Among 145 pts who have data on response, 9 had partial response, 41 had stable disease and 95 had progressive disease. BRAFV600E mutation is associated with a higher probability of response (OR = 6.89, 95% CI: 1.64 – 28.94, p-value = 0.01) and pts enrolled on matched clinical trials had a higher probability of response (OR = 6.23; 95% CI: 1.24 – 31.09, p-value = 0.03). However, increased response did not translate to improved OS. No survival differences were appreciated based on a pts race or BMI. Conclusions: CTNNB1, BRAFV600E &amp; NRAS mutations may have prognostic implications in YOCRC. Pts enrolled on mutation specific clinical trials did not achieve improved outcomes compared to unselected trials, highlighting aggressive biology, current lack of therapeutic targets and need for novel drug development in sporadic YOCRC.

Timing of specialized palliative care integration and its impact on quality of end-of-life care indicators among Latin American cancer patients.

e24168 Background: Prior studies have shown that specialized palliative care (SPC), when integrated early during the disease trajectory, improves the quality of end-of-life care among advanced cancer patients. However, those studies were conducted in large academic cancer centers in developed countries, where the availability of human and structural SPC resources is extensive. Little is known about how the timing of SPC may affect end-of-life quality care indicators in other settings of the globe. We aimed to examine the timing of SPC over a 4-year period and how it was associated with ASCO end-of-life quality care indicators. Methods: Retrospective cohort study of all adult cancer patients referred to the SPC team and who died at Hospital Israelita Albert Einstein, Sao Paulo, Brazil, between April 2017 and April 2021.Data onpatient demographics, clinical characteristics, timing of SPC integration as measured as the median interval between first SPC consult to death (SPC1-D), and ASCO end-of-life quality care indicators were retrieved. Results: Among 292 deceased cancer patients (52% female; median age = 67; 70% ECOG ≥3), the median SPC1-D interval was 24 days. There was a decrease in SPC1-D interval in the pandemic years (April 2017 through March 2018 = 27 days; April 2018 through March 2019 = 39 days; April 2019 through March 2020 = 23 days; April 2020 through April 2021 = 15 days; p = .02). 164 (56%) had an SPC1 &lt; 30 days before death. Patients who had an SPC1 &gt; 30 days before death were less likely to receive chemo and targeted therapy within the last 30 days of life (Table 1). Conclusions: Integration of SPC occurred late, especially during the pandemic years. Nevertheless, earlier SPC1 improved treatment aggressiveness in end-of-life. Further efforts are needed to enhance early SPC referrals in resource-limited settings.[Table: see text]