Deal, Allison

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.

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.

PURPOSE Many trials ask patients to complete patient-reported outcome measures (PROMs) via the web, excluding patients unable to use/access the Internet. The PRO-TECT trial (AFT-39, ClinicalTrials.gov identifier: NCT03249090 ) also offered a telephone interface option (interactive voice response [IVR]). We compared patients choosing IVR versus web on alert rates to nurses and clinical outcomes to determine if a telephone option can close disparities in symptom management. METHODS PRO-TECT randomized 26 community oncology practices to the PROM intervention arm where concerning symptoms generated automated alerts to nurses. IVR and web patients were compared for social determinants of health (SDOH) using analysis of variance and chi-square tests. After accounting for clustering and confounders, we used generalized estimating equations to compare alert rates, mixed models for quality of life (QOL) at 3 months, and Cox regression for emergency visits and survival at 12 months. RESULTS Among 593 patients, 215 (36%) chose IVR and 378 (64%) chose web. IVR patients were older (65.2 v 60.8 years) and were more often rural residents (32% v 23%), Black (27% v 11%), and with less education (54% v 27% ≤high school; all P < .01). Patients choosing IVR had more surveys with concerning symptoms (49% v 37%) and nurses felt clinical attention was warranted more often (4.8 surveys v 3.4 surveys; all P < .001) but ultimately experienced similar benefits as web in QOL, emergency visits, and survival. CONCLUSION One third of community patients choose a telephone option over the web for reporting PROMs during cancer care. These patients are disproportionately from SDOH backgrounds at risk of poor clinical outcomes and have higher symptom management needs but ultimately experience similar clinical benefits as patients choosing the web. PROM programs should offer web alternatives to close disparities in symptom management.

PURPOSE Financial toxicity (FT) affects 20% of cancer survivors and is associated with poor clinical outcomes. No large-scale programs have been implemented to mitigate FT. We evaluated the effect of monthly FT screening as part of a larger patient-reported outcomes (PROs) digital monitoring intervention. METHODS PRO-TECT (AFT-39) is a cluster-randomized trial of patients undergoing systemic therapy for metastatic cancer. Practices were randomly assigned 1:1 to digital symptom monitoring (PRO practices) or usual care (control practices). Digital monitoring consisted of between-visit online or automated telephone patient surveys about symptoms, functioning, and FT (single-item screening question from Functional Assessment of Chronic Illness Therapy-COmprehensive Score for financial Toxicity) for up to 1 year, with automated alerts sent to practice nurses for concerning survey scores. Clinical team actions in response to alerts were not mandated. The primary outcome of this planned secondary analysis was development or worsening of financial difficulties, assessed via the European Organisation for Research and Treatment of Cancer QLQ-C30 financial difficulties measure, at any time compared with baseline. A randomly selected subset of patients and nurses were interviewed about their experiences with the intervention. RESULTS One thousand one hundred ninety-one patients were enrolled (593 PRO; 598 control) at 52 US community oncology practices. Overall, 30.2% of patients treated at practices that received the FT screening intervention developed, or experienced worsening of, financial difficulties, compared with 39.0% treated at control practices ( P = .004). Patients and nurses interviewed stated that FT screening identified patients for financial counseling who otherwise would be reluctant to seek, or unaware of the availability of, assistance. CONCLUSION In this report of a secondary outcome from a randomized clinical trial, FT screening as part of routine digital patient monitoring with PROs reduced the development, or worsening, of financial difficulties among patients undergoing systemic cancer therapy.

180 Background: Financial toxicity affects 20% of cancer survivors and is associated with decreased treatment adherence and poor clinical outcomes. No large-scale programs have been implemented to mitigate financial toxicity among patients undergoing cancer treatment. We evaluated the effect of monthly patient-reported financial toxicity screening as part of a larger digital monitoring intervention. Methods: PRO-TECT (AFT-39) is a cluster-randomized trial of patients undergoing systemic therapy for metastatic cancer. Practices were randomized 1:1 to digital symptom monitoring with patient-reported outcomes (“PRO practices”) or usual care (“control practices”). Digital monitoring consisted of between-visit online or automated telephone patient surveys containing symptom, functioning, and financial toxicity screening questions for up to one year, with automated alerts sent to practice nurses for concerning survey scores. Clinical team actions in response to alerts were not mandated. The primary outcome of this analysis was development or worsening of financial difficulties, assessed via the EORTC QLQ-C30 (“Has your physical condition or medical treatment caused you financial difficulties?”), at any time compared to baseline. A randomly selected subset of patients and nurses were interviewed about their experiences with the intervention. Results: 1,191 patients were enrolled (593 PRO; 598 control) at 52 US community oncology practices. Overall, 30.2% of patients treated at practices that received the intervention developed, or experienced worsening of, financial difficulties, compared to 39.0% of patients treated at control practices (p = 0.01). Patients and nurses interviewed stated that financial toxicity screening identified patients for financial counseling who otherwise would be reluctant to seek, or unaware of the availability of, assistance. Conclusions: Screening for financial toxicity as part of routine digital patient monitoring with PROs reduces the development, or worsening, of financial difficulties among patients undergoing systemic cancer therapy. Clinical trial information: NCT03249090.

349527 Background: Symptoms are common during cancer care but often go undetected. Digital systems that elicit patient-reported outcomes (PRO) surveys may detect symptoms early and prompt clinicians to intervene, thereby alleviating suffering and averting complications. Methods: In a cluster-randomized trial, U.S.-based community oncology practices were randomized 1:1 to digital symptom monitoring with PRO surveys, or to usual care control. Patients receiving systemic treatment for metastatic cancer were eligible. At PRO practices, participants were invited to complete a weekly survey via web or automated telephone system for up to one year, including questions about nine common symptoms, performance status, and falls. Severe or worsening symptoms triggered electronic alerts to care team nurses, and reports showing longitudinal symptom data were available to oncologists at visits. Pre-specified secondary outcomes included impact on physical function, symptom control, and health-related quality of life (HRQL). The primary outcome of survival is not yet mature. Results: At 52 practices, 1,191 patients were eligible and enrolled (593 PRO; 598 control). Clinically meaningful benefits were experienced in physical function by 13.8% more patients with PRO versus control (P=0.009); symptom control by 16.1% (P=0.003); and HRQL by 13.4% (P=0.006). Mean changes from baseline were superior with PRO versus control for physical function (mean difference 2.47, 95% CI 0.41-4.53; P=0.02), symptom control (2.56, 0.95-4.17; P=0.002), and HRQL (2.43, 0.90-3.96; P=0.002). Patients completed 20,565/22,486 (91.5%) of expected weekly PRO surveys. Conclusions: Digital symptom monitoring during cancer treatment confers clinical benefits. Clinical trial information: NCT03249090.

PURPOSE There is increasing interest in implementing digital systems for remote monitoring of patients’ symptoms during routine oncology practice. Information is limited about the clinical utility and user perceptions of these systems. METHODS PRO-TECT is a multicenter trial evaluating implementation of electronic patient-reported outcomes (ePROs) among adults with advanced and metastatic cancers receiving treatment at US community oncology practices (ClinicalTrials.gov identifier: NCT03249090 ). Questions derived from the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) are administered weekly by web or automated telephone system, with alerts to nurses for severe or worsening symptoms. To elicit user feedback, surveys were administered to participating patients and clinicians. RESULTS Among 496 patients across 26 practices, the majority found the system and questions easy to understand (95%), easy to use (93%), and relevant to their care (91%). Most patients reported that PRO information was used by their clinicians for care (70%), improved discussions with clinicians (73%), made them feel more in control of their own care (77%), and would recommend the system to other patients (89%). Scores for most patient feedback questions were significantly positively correlated with weekly PRO completion rates in both univariate and multivariable analyses. Among 57 nurses, most reported that PRO information was helpful for clinical documentation (79%), increased efficiency of patient discussions (84%), and was useful for patient care (75%). Among 39 oncologists, most found PRO information useful (91%), with 65% using PROs to guide patient discussions sometimes or often and 65% using PROs to make treatment decisions sometimes or often. CONCLUSION These findings support the clinical utility and value of implementing digital systems for monitoring PROs, including the PRO-CTCAE, in routine cancer care.

Abstract Approximately 90% of limited-stage Hodgkin lymphoma (HL) patients are projected to be cured with standard therapy, but many do not live their expected life span because of late treatment–related complications. New treatment paradigms are needed to reduce the use of radiation therapy (RT) as well as conventional chemotherapy drugs while improving upon current standard-of-care survival outcomes. In this phase 2 multicenter study, patients with non-bulky limited-stage HL received doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by brentuximab vedotin (BV) consolidation. Forty-one patients were enrolled, and patient characteristics included median age of 29 years (range, 19 to 67 years), 58% were female, 45% had unfavorable disease, and 98% had stage II disease. Based on positron emission tomography (PET)–based risk stratification, patients received 2 to 6 cycles of ABVD followed by 6 cycles of BV. After ABVD followed by BV, 95% of evaluable patients (37 out of 39; 95% confidence interval [CI], 83%-99%) achieved PET-negative status. In the intent-to-treat patient population, the estimated 3-year progression-free survival (PFS) rate was 92%, and the overall survival (OS) rate was 97%, with a median follow-up of 47 months. All 37 patients who achieved negative PET status after BV consolidation effectively avoided RT and remain in remission with estimated 3-year PFS and OS rates of 100%. In conclusion, BV demonstrates encouraging clinical activity when it follows ABVD therapy in limited-stage HL. Early incorporation of BV may reduce the use of RT as well as conventional chemotherapy drugs while achieving favorable survival outcomes in risk-stratified patients with non-bulky limited-stage HL. This trial was registered at www.clinicaltrials.gov as #NCT01578967.

Abstract Background: Treatment of Hodgkin lymphoma (HL) requires a careful balance between providing enough therapy to cure the disease and avoiding unnecessary treatment that could result in excessive long-term treatment-related complications. The preferred treatment option for limited stage non-bulky HL currently involves the use of combined chemotherapy and involved-field radiation therapy. Given the unclear overall survival advantage and the long-term side effects associated with consolidative radiation, the use of this modality remains one of the most controversial topics in the treatment of HL. Therefore, alternative consolidation approaches are worthy of exploration for treatment of limited stage non-bulky HL. Brentuximab vedotin has been associated with favorable response rates in patients with relapsed or refractory HL. We hypothesize that brentuximab vedotin may be safe and effective in eradicating residual disease after induction chemotherapy and may potentially replace radiation therapy for consolidation in patients with newly diagnosed limited stage non-bulky HL. Methods: In this phase 2 multicenter study, patients with non-bulky (< 7.5 cm) stage I or II HL are being enrolled to determine the efficacy and safety of brentuximab vedotin when administered for consolidation after a standard chemotherapy with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) (ClinicalTrials.gov #NCT01578967). The primary objective of the study is to estimate the proportion of patients who achieve PET-negative disease (Deauville score of 2 or less) after induction chemotherapy followed by consolidation with brentuximab vedotin. Involved-field radiation is recommended only if the PET scan is positive at the completion of therapy with brentuximab vedotin. Patients received 2 to 6 cycles of ABVD based on their baseline risk factors and the interim PET scan result; patients with favorable disease with negative interim PET received 2 cycles, favorable disease with positive interim PET or unfavorable disease with negative interim PET received 4 cycles, and unfavorable disease with positive interim PET received 6 cycles of ABVD. Approximately 6 to 8 weeks after the induction chemotherapy, 1.8 mg/kg of brentuximab vedotin was given every 3 weeks for 6 cycles for consolidation. Results: Interim analysis was performed per protocol for futility and safety after 15 evaluable patients were enrolled since April 2012. Out of 15 evaluable patients, 8 patients have completed 6 cycles of brentuximab vedotin, and the remaining 7 patients are currently under active treatment. The median age was 28 years (range 19 – 58), and 7 patients (47%) presented with unfavorable disease defined by the presence of B symptoms, ESR > 50, or > 3 sites of disease. All patients had masses measuring less than 7.5 cm in diameter except one patient who requested an exception to the eligibility criteria for a conglomerate mediastinal mass measuring 10 cm. No grade 3 or above adverse events have been observed with brentuximab vedotin therapy. No grade 2 or above peripheral neuropathy or pulmonary toxicity has been reported. Ten out of 12 patients, who completed ABVD, achieved PET-negative disease after 2 cycles of ABVD, and all 7 patients who completed brentuximab vedotin achieved PET-negative disease and remain in remission with a median follow-up of 7.6 months (range 5.6 – 15). Thus far, none of the treated patients on this protocol required consolidative radiation therapy. Conclusion: In this interim analysis of 15 patients with newly diagnosed limited stage non-bulky HL, brentuximab vedotin as consolidation therapy demonstrates promising safety and clinical activity following ABVD. Enrollment is currently open with the target accrual of 40 patients to assess the feasibility of achieving PET-negative disease and thereby avoiding radiation therapy in at least 85% of patients who receive ABVD followed by brentuximab vedotin consolidation. Table: PET results in HL patients who received ABVD followed by BV Consolidation Interim-PET2 (n = 12) Post ABVD (n = 12) Post BV (n = 7) Deauville 1 0 1 4 Deauville 2 10 11 3 Deauville 3 2 0 0 Deauville ≥ 4 0 0 0 PET, positron emission tomography; HL, Hodgkin lymphoma; ABVD, doxorubicin, bleomycin, vinblastine, dacarbazine; BV, brentuximab vedotin; Interim-PET-2, PET scan after 2 cycles of ABVD; Post ABVD, PET scan after 2 to 6 cycles of ABVD; Post BV, PET scan after 6 cycles of brentuximab vedotin Disclosures Park: Seattle Genetics: Research Funding; Teva: Research Funding; Janssen: Travel, Travel Other. Off Label Use: Brentuximab vedotin in previously untreated Hodgkin lymphoma patients.