Lee, Minji K.

Financial toxicity is a significant but often overlooked consequence of cancer for adolescents and young adults (AYAs, 15–39 years old), who face limited savings, unstable employment, and insurance gaps that heighten financial stress. As part of a larger initiative to determine whether our cancer center can use an existing social drivers of health (SDOH) screening process to identify patients who may benefit from targeted supportive interventions, we sought to characterize financial strain, toxicity, and SDOH needs in AYAs treated in our cancer center and compare them to both younger and older cancer patients. This is a cross-sectional observational study at Mayo Clinic of patients with an oncology-related department visit between 8 September 2023–4 June 2024 (N = 81,731) who completed routine institutional electronic screenings for financial strain and SDOH. Survey items assessed financial strain, transportation barriers, and food insecurity; institutional billing data captured financial toxicity (unresolved balances, collection referrals, write-offs). AYAs (n = 5655) were more likely than non-AYAs to report medium/high financial strain, have unpaid debt, or have an unresolved balance, referral to a collection agency, or bad debt write-off, with nearly double the odds of medium/high financial strain compared to patients over 40 (OR 2.02, 95% CI 1.84–2.23, p < 0.001). Within AYAs, ages 26–32 bore the greatest burden: 24.2% in the medium/high-risk category, 9.4% with unresolved billing issues or collections, and 11.6% reporting food insecurity. These findings identify AYAs—particularly those 26–32—as a distinct high-risk group for financial toxicity and health-related social needs, underscoring the need for targeted interventions, tailored financial navigation, and policy efforts to reduce economic barriers to care. Future research should evaluate the effectiveness of these interventions in mitigating financial toxicity, addressing health-related social needs, and improving patient outcomes in this population.

Background/Objectives: The PRO-CTCAE Average Composite Score (ACS), calculated as the mean of PRO-CTCAE composite scores, summarizes overall symptom and side effect burden. This study evaluated the test–retest reliability, responsiveness to change, known-groups validity, and sensitivity to group differences in the ACS. Methods: Analyses used the original PRO-CTCAE validation dataset, including lung (n = 174), breast (n = 222), and head and neck (n = 139) cancer cohorts, and data from the COMET-2 randomized phase III trial comparing cabozantinib (n = 53) and mitoxantrone–prednisone (n = 54) in men with previously treated prostate cancer. Test–retest reliability was assessed using intraclass correlation coefficients (ICCs) from two-way mixed-effects models for agreement. Responsiveness was evaluated by relating ACS change scores (Visit 1 minus follow-up Visit 2) to patient-reported global ratings of change (GRC; worsened, unchanged, or improved) using standardized response means (SRMs) and Jonckheere–Terpstra trend tests. Known-groups validity was examined by comparing mean ACS values between ECOG performance status groups (0–1 vs. 2–4). Sensitivity to treatment group differences was assessed using model-based area-under-the-curve (AUC) comparisons of longitudinal ACS trajectories. Results: Test–retest reliability was acceptable, with ICCs among GRC-defined stable patients of 0.80 (95% CI: 0.70–0.87) in lung cancer, 0.84 (95% CI: 0.77–0.89) in breast cancer, and 0.77 (95% CI: 0.63–0.86) in head and neck cancer; ICCs based on assessments completed one day apart ranged from 0.88 to 0.90. The ACS demonstrated responsiveness, with SRMs of 0.30/0.15/−0.37 (lung), 0.29/0.14/−0.40 (breast), and −0.01/−0.20/−0.56 (head/neck) for improved/no-change/worsened groups, respectively, and significant monotonic trends across GRC categories (all p < 0.01). Known-groups validity was supported by conceptually expected differences in ACS values across distinct levels of self-reported patient-reported physical functioning and ECOG performance status categories. Mean ACS values were lower among patients with good versus limited physical functioning (0.71 vs. 1.23 in lung cancer, 0.52 vs. 1.19 in breast cancer, and 0.69 vs. 1.29 in head and neck cancer) and among patients with ECOG PS 0–1 versus 2–4 (0.93 vs. 1.31, 0.74 vs. 1.22, and 0.90 vs. 1.06, respectively). In COMET-2, higher symptom burden was detected in the cabozantinib arm compared with the mitoxantrone–prednisone arm (AUC difference = 1.5, 95% CI: 0.2–2.8, p = 0.02). Conclusions: The ACS demonstrated acceptable test–retest reliability, responsiveness, and known-groups validity across multiple cancer populations. These findings support its use as a complementary summary measure of overall symptomatic adverse event burden alongside individual symptom-level analyses.

Abstract Background Older adults remain underrepresented in prospective trials of immunotherapy for advanced lung cancer. To estimate pembrolizumab adverse events, we conducted a multicenter, nonrandomized, open-label phase 2 trial of oncologist-choice first-line pembrolizumab with or without chemotherapy for older adults with advanced lung adenocarcinoma. Methods Alliance for Clinical Trials in Oncology A171901 enrolled patients aged 70 years and older with stage IV or recurrent lung adenocarcinoma starting oncologist’s choice of first-line pembrolizumab with or without carboplatin and pemetrexed. The primary endpoint was the proportion of patients experiencing a solicited grade 3 or greater adverse event within 6 months. Secondary endpoints included overall survival, quality of life, and association of a geriatric assessment toxicity risk score with severe adverse events. Results Among 95 evaluable patients, 43 (45.3%) received pembrolizumab and 52 (54.7%) received pembrolizumab plus chemotherapy. Median age was 77 years (range = 70-92 years); 11.6% had an E Performance Status of 2 or higher. During 6 months of treatment, 25.6% (95% CI = 13.5% to 41.2%) experienced a solicited grade 3 or greater adverse event in the monotherapy group and 42.3% (95% CI = 28.7% to 56.8%) in the combination group. Median overall survival was 16.4 months (95% CI = 10.1 to not estimable) with monotherapy and 29.9 months (95% CI = 16.4 to not estimable) with combination therapy. Quality of life worsened during treatment. The geriatric assessment toxicity risk score was not associated with severe adverse events with pembrolizumab with or without chemotherapy. Conclusions Older adults with advanced lung adenocarcinoma receiving pembrolizumab with or without chemotherapy had comparable adverse event rates to those in prior registration trials that excluded medically frail patients. These findings can inform shared decision making and support inclusion of older adults in future trials. Clinical Trial NCT04533451 (https://clinicaltrials.gov/study/NCT04533451)

Background/Objectives. Decades of research have failed to uncover effective approaches to prevent chemotherapy-induced peripheral neuropathy (CIPN), a common side effect of neurotoxic chemotherapy. Increased interest in placebo response as a potentially under-recognized confounder in CIPN trials was recently sparked by the results of a multisite NCI-funded phase II-III CIPN prevention study of duloxetine, a promising serotonin–norepinephrine reuptake inhibitor that enhances pain-inhibitory mechanisms within the central nervous system. Study findings revealed high and nearly equivalent response rates in three randomized treatment groups—little to no CIPN was reported by 65.2%, 66.0%, and 68.0% of study participants who received duloxetine 30 mg, 60 mg, or placebo treatment, respectively. Methods. We performed a meta-analysis of placebo response rates from seven randomized, double-blinded, placebo-controlled trials conducted over the past 20 years and comprising 191 placebo participants that were specifically testing interventions for oxaliplatin- and paclitaxel-induced peripheral neuropathy and that serially collected patient responses on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Chemotherapy-Induced Neuropathy questionnaire. Additionally, we sought to identify trial- and patient-specific factors that predicted higher placebo response rates from a participant-level pooled analysis. Results. The placebo response rate was 10.0% [95% CI: 5.8%, 16.6%] when response was defined more conservatively as patients reporting no neuropathy at all. When the placebo response was defined more broadly based on patients reporting no or a little neuropathy, the placebo response rate was higher (39.6% [95% CI: 27.4%, 53.2%]). Male participants, receipt of oxaliplatin, and a 2:1 randomization ratio favoring the intervention arm were individually associated with a higher placebo response. Conclusions. High placebo response rates can threaten scientific progress toward identifying effective treatments for cancer treatment-associated side effects, like CIPN. Careful attention to study design factors, participant eligibility, and patient and research staff expectations may help to minimize placebo response rates in future CIPN intervention studies.

PURPOSE The primary objective of this randomized, double-blind, placebo-controlled, multicenter phase II study (Alliance A221805) was to screen two doses of duloxetine for preventing sensory oxaliplatin-induced peripheral neuropathy (OIPN). METHODS Participants were randomly assigned 1:1:1 to receive once daily 30 mg duloxetine, 60 mg duloxetine, or placebo. Eligible participants had stage II to III colorectal cancer and no baseline neuropathy, had Eastern Cooperative Oncology Group performance status 0-2, were age 25 years and older, and received oxaliplatin via one of the following doses and schedules: 85 mg/m 2 every 2 weeks (6 or 12 doses) or 130 mg/m 2 every 3 weeks (4 doses). Duloxetine/placebo was taken once daily beginning day 1 of cycle 1 and continued for 17 weeks. The primary end point, a composite response reflecting sensory OIPN symptom severity and onset, was measured in weeks 19-21 using a validated participant-reported outcome survey assessing extremity numbness, tingling, and pain. Response was defined as a participant-reported highest score of ≤2 (ie, 1 = not at all; 2 = a little) on survey items. To be evaluable for the response end point, eligible participants must have initiated oxaliplatin and submitted ≥1 postbaseline OIPN survey. RESULTS Of the 199 participants (n = 66, 30 mg duloxetine; n = 66, 60 mg duloxetine; n = 67, placebo), 46, 47, and 50 (N = 143, 71.8%), respectively, were evaluable for primary end point analysis based on modified intention-to-treat criteria. Participant mean age was 55.1 years (standard deviation = 10.4). Most were White (n = 113, 80.7%) and male (n = 82, 58.6%). The proportion of responders among those receiving placebo (68.0%) was similar to those receiving duloxetine 30 mg (65.2%) or 60 mg (66.0%). Duloxetine adherence rates, measured via pill counts—30 mg (54%), 60 mg (57%), and placebo (59%) groups—were low (<75%). CONCLUSION Duloxetine is not more promising than placebo for preventing sensory OIPN.

Background: The PRO-CTCAE provides patient-reported data on symptomatic AEs. A summary metric—the ACS—reflecting total AE burden can be calculated by averaging AE-level composite scores at a given timepoint for each participant. This study investigated the psychometric properties and interpretability of this PRO-CTCAE ACS in patients with breast, lung, or head/neck cancers. Methods: We conducted a secondary analysis of a PRO-CTCAE validation dataset comprising 940 adults undergoing chemotherapy or radiation therapy (clinicaltrials.gov: NCT02158637). We focused on empirically recommended symptom terms for three cancer sites. Analyses included Spearman’s correlations, coefficient alpha, and eigenvalues from the correlation matrices, confirmatory factor analysis (CFA), and principal component analysis (PCA). Latent profile analysis (LPA) was used to assess ACS interpretability in the lung cohort. Results: Mean composite score inter-correlations were moderate (0.30–0.35), and coefficient alphas were high (0.81–0.91). Eigenvalue ratios and CFA supported retention of a single factor/component, with suitable model fit indices. ACS correlated highly with factor scores and the first principal component from the PCA. Reduced sets of terms produced reliable scores that closely approximated the full set scores and aligned with external criteria. LPA in the lung subgroup identified four latent classes; ACS differentiated high vs. low symptom burden groups but did not distinguish the two groups expressing distinct symptom profiles. Conclusion: The ACS demonstrated structural validity through adequately fitting linear factor models and effectively summarized symptomatic AE burden. However, similar ACS values may mask clinically distinct symptomatic AE profiles, underscoring the value of both summary metrics and profile-based approaches.

Abstract The Patient‐Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO‐CTCAE) was developed by the US National Cancer Institute to allow patients to directly report their side effects, enhancing the accuracy and patient‐centeredness of cancer clinical trial adverse event reporting. Clinician‐based reporting often misses the full range of patient symptoms, resulting in underreporting of side effects. The selection of adverse events for patient reporting must be defined in advance and consistently applied across all study arms. Investigators can use core symptom sets, including diarrhea, fatigue, and nausea, alongside tailored items specific to the treatments being studied. PRO‐CTCAE has demonstrated similar scores across electronic, paper‐based, and automated telephone administration methods. PRO‐CTCAE administration typically occurs before start of treatment and regularly throughout treatment, with the administration frequency tailored to the expected trajectory of side effects. Ensuring high survey completion rates is essential for PRO‐CTCAE success. Standard reporting can include tabular reporting of the proportion of patients with any (score ≥1) and high (score ≥3) levels of symptoms at the individual item level. A baseline‐adjustment approach should be applied to account for symptoms before start of treatment to isolate treatment‐emergent adverse events. The distribution of PRO‐CTCAE scores at each time point can be visualized using stacked bar charts. PRO‐CTCAE integration into cancer clinical trials is crucial for capturing a comprehensive range of treatment‐related symptomatic adverse events and improving the evaluation of therapy tolerability. Ongoing research continues to refine its implementation, supported by regulatory guidance.

678 Background: Financial toxicity (FT) represents a challenge for cancer patients that impacts treatment decisions, patient satisfaction, and quality of life. Social determinants of health (SDoH) screening may predict who is at risk of FT and could potentially benefit from financial interventions. Methods: This is a retrospective study of all cancer patients presenting to Mayo Clinic sites between Sept 2023 – Jun 2024. Patients completed SDoH questionnaires and were given risk scores of Low Risk, Medium Risk, and High Risk for SDoH categories: Financial Strain Risk, Transportation Risk, and Food Insecurity Risk. Patient financial data including active debt amounts, insurance coverage, and financial aid were collected. Patients with pancreatic ductal adenocarcinoma (PDAC) were compared to those with pancreatic neuroendocrine tumors (PNET) and patients with other cancers (Others). Categorical variables were compared with Pearson's Chi-squared test, continuous variables with Kruskal-Wallis rank sum test. P values < 0.05 were considered significant. Results: Data was obtained from 88,039 patients, 2,607 of whom had PDAC and 449 had PNET. Compared to PDAC patients, PNET patients and Others were more likely to have Medium/High risk scores for Financial Strain Risk (6% vs 6.5% and 8.5%, respectively) and Food Insecurity (1.7% vs 3.8% and 3.2%) (Table). There was no statistically significant difference in median medical debt and need of financial assistance between the groups. Among PDAC patients, there were differences in distributions among race, primary language spoken, and patient electronic record access depending on Financial Risk categories. African American patients had the greatest proportion of Medium/High risk (12.9%) compared to Asian (4.4%) and White (5.8%) patients (P<0.001). Among patients with English as their primary language, 64.9% had Low Risk scores compared to 27.7% with other primary languages (P<0.001). Patients with electronic record access were more likely to report High Risk scores (6.9%) compared to those without access (1.6%). Conclusions: Per patient responses collected, PDAC patients presenting to our center have lower risk of financial strain and similar medical debt levels compared to the remainder of cancer patients. Among PDAC patients, higher financial strain was experienced by non-whites (7.9% vs 5.8%). Diagnosis PDAC (N=2607) PNET (N=449) Other (N=84983) p value Current Financial Risk (Grouped) < 0.001 - Low Risk 1662 (63.8%) 304 (67.7%) 59298 (69.8%) - Medium/High Risk 157 (6.0%) 29 (6.5%) 7209 (8.5%) - Unknown/Missing 788 (30.2%) 116 (25.8%) 18476 (21.7%) Food Insecurity Risk < 0.001 - Low Risk 1764 (67.7%) 308 (68.6%) 63235 (74.4%) - Medium Risk 45 (1.7%) 17 (3.8%) 2703 (3.2%) - Unknown/Missing 798 (30.6%) 124 (27.6%) 19045 (22.4%) Median Active Debt in USD 1102.230 1020.010 1141.135 0.593

ABSTRACTObjectivesThis study aimed to compared Patient‐Reported Outcomes Measurement Information System (PROMIS) anxiety, depression, and anger item bank among Korean, US and Dutch general population.MethodsBetween December 2021 and January 2022, we surveyed representative Korean participants (N = 2699). Then we compared the mean T‐scores of PROMIS anxiety, depression, and anger full items bank among Korean, US (N = 1696) and the Dutch (N = 1002) populations. Differential item‐functioning (DIF) analyses were also performed. We also compared each score by age group, sex, presence of comorbidities, and general health status.ResultsIn Korean, the mean T‐scores for anxiety, depression, and anger were 45.3 (standard deviation [SD] = 11.6), 48.4 (SD = 11.2), and 44.9 (SD = 12.6), respectively. Among the general population in Korea, patients aged 35–44 years and those with comorbidities had higher anxiety, depression, and anger scores. In the DIF analyses between the US and Korean populations, 28%, 32%, and 45% were flagged for uniform or non‐uniform DIF in anxiety, depression and anger, respectively.ConclusionsConsidering the cultural differences, we recommend using a harmonized approach that includes country‐specific reference values while retaining a standardized core set of items to enable cross‐country comparability.