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e16246 Background: First line systemic therapy for advanced hepatocellular carcinoma (HCC) includes immune checkpoint inhibitor (ICI) combination therapy, with tyrosine kinase inhibitors (TKIs), lenvatinib or cabozantinib, commonly used as second line therapy. However, there is limited data comparing efficacy of TKIs following first line ICI therapy. In the present study, we compared survival and risk of hospitalization in a propensity score matched analysis of patients who received lenvatinib or cabozantinib following progression on first line ICI therapy in patients with advanced HCC. Methods: We performed a retrospective cohort study using data from TriNetX, a healthcare database of over 150 million patients in the United States. We identified adult patients with a history of HCC who received atezolizumab plus bevacizumab (A+B) or durvalumab plus tremelimumab (D+T) as first line treatment. We then stratified patients by use of lenvatinib or cabozantinib in the subsequent line setting. Propensity score matching (PSM) was conducted between those who received lenvatinib and those who received cabozantinib, matching for demographic factors (age, sex, race), clinical characteristics (history of alcohol use, ascites, esophageal varices, or viral hepatitis), and laboratory parameters [platelets, albumin, bilirubin, INR and alpha-1-fetoprotein (AFP)]. Results: We identified 416 patients who were initially treated with either A+B or D+T, with 327 patients receiving A+B and 89 patients receiving D+T. Of these, 336 patients (80.8%) subsequently received lenvatinib and 80 patients (19.2%) received cabozantinib. Baseline characteristics of demographic factors, clinical characteristics, and laboratory parameters were comparable between patients in the lenvatinib arm and cabozantinib arm with all standardized mean differences (SMD) < 0.10. After PSM, 76 patients were included in the analyses, with all variables adequately balanced. There was no significant difference in the risk of hospitalization between those receiving lenvatinib or cabozantinib at 3 months [31.6% vs 34%, odds ratio (OR) 1.13, 95% confidence interval (CI) 0.57-2.2]. There was also no significant difference in mOS between those receiving lenvatinib and cabozantinib [9.5 vs 9.0 months, hazard ratio (HR) 1.03, 95% CI 0.62-1.7]. Conclusions: In patients with HCC who received lenvatinib or cabozantinib as second-line therapy following first-line ICI combination therapy, we found no significant differences in rate of hospitalization or survival. These findings suggest that either option may be appropriate, and decisions may be based in side effect profile and patient preferences. Prospective studies will be important to further assess differences in patient outcomes.

ABSTRACT Introduction Hairy cell leukemia (HCL) is an uncommon hematopoietic stem cell disease known to have an underlying somatic BRAF V600E driver mutation. Currently, the most accepted treatment is five or seven consecutive days of outpatient infusion of cladribine (e.g., continuous infusion), despite frequent antibiotic use and hospitalization with this regimen. As a result, a few investigators have adopted weekly infusion of cladribine with similar or improved results and fewer side effects. Methods We conducted a retrospective, single‐institution cohort study of 36 treatment‐naïve patients with HCL treated at the University of Colorado Hospital. Eighteen patients received intermittent weekly cladribine (intermittent cladribine [IC]) for 5–7 doses and 18 received standard daily cladribine (continuous cladribine [CC]) over 5–7 days. We report clinical cohort characteristics, response rates, progression‐free survival, overall survival, toxicity, hospitalization rates, and measurable residual disease monitoring in select patients using peripheral blood quantitative BRAF V600E PCR. Results We report here our experience with 18 patients with newly diagnosed BRAF ‐mutated HCL treated with weekly cladribine at a single institution compared to 18 HCL patients who received continuous infusions. Baseline hematologic parameters and overall survival were comparable between groups ( p = 0.1135), but there was a higher rate of complete remission for patients treated with IC (94.4% vs. 61.1%) with significantly improved progression‐free survival ( p < 0.0001). We observed comparable rates of neutropenia, neutropenic fever, antibiotic use, and G‐CSF administration. There were fewer hospitalizations for patients treated with IC (4/18) compared to patients treated with CC (6/18). Rituximab exposure differed between groups, with 72% of patients in the IC cohort receiving rituximab compared with 27.2% in the CC cohort (although treatment status was documented for only 66.7% of patients in the CC cohort). Peripheral blood BRAF V600E allele burden significantly declined and correlated with clinical remission, but this was only performed in select patients who were treated in recent years. Conclusions In this retrospective analysis, IC dosed weekly was associated with improved progression‐free survival and higher rates of complete remission compared to CC with comparable toxicity and fewer hospitalizations. These findings suggest a potential clinical benefit from this regimen. However, interpretation of these findings is limited by the non‐randomized design and differences in rituximab exposure between groups, which may have contributed to the observed outcomes and limited definitive conclusions. Trial Registration: The authors have confirmed clinical trial registration is not needed for this submission

ABSTRACT Introduction Community health workers (CHWs) help patients navigate community resources. CHW programs can improve health outcomes and reduce healthcare utilization, but identifying eligible patients is challenging. We developed an electronic health record (EHR)‐based algorithm trained to predict referrals to a CHW program. Our objective was to evaluate whether an algorithm trained on historical referrals identifies a subgroup of patients that differs from the subgroup identified through questionnaire‐based health‐related social needs (HRSN) screening alone. Methods This analysis used data from Mayo Clinic primary care patients in Southeast Minnesota. We developed a gradient boosted time‐to‐event model that incorporated demographics, diagnoses, HRSN questionnaire responses, and HRSNs derived from clinical notes using natural language processing. We compared the characteristics of algorithm‐identified patients with those identified through questionnaires and assessed the variable importance of model features. Results The algorithm had AUC: 0.87 in the training and 0.92 in the hold out set. Patients flagged by the algorithm tended to use interpreter services more commonly (12.6% vs. 1.3%), have a non‐English preferred language (14.1% vs. 2.3%), and have more instances of health literacy documented (5.36 vs. 1.29) compared to patients identified by the HRSN questionnaire. Only 47.0% of patients flagged by the algorithm had responded to the HRSN questionnaire within 2 years. Variable importance was highest for health literacy and financial strain from unstructured notes. Conclusions The algorithm is a chart‐review prioritization tool for referral to the CHW program for patients that may overcome challenges to identifying patients with HRSNs, especially when questionnaire data is incomplete.

e12601 Background: Mammography remains the standard modality for breast cancer (BC) screening but has several limitations. There is a critical need for minimally invasive markers that can aid in distinguishing benign, non-invasive lesions from those likely to progress to invasive BC. Platelets are nature’s transport mechanism for delivery of growth factors and inhibitors. Assaying the platelet proteome, Hessian Labs developed HeLP (Hessian Labs Personalized) test designed to identify early malignancy, as well as its grade, and invasiveness. The test is based on a discovery that platelets sequester oncogenic regulators against a concentration gradient in plasma early in tumor development. Hence, it has the potential to differentiate benign from invasive BC at various stages, stratifying the need for intervention. Methods: Platelet samples from 120 women with BC were analyzed using a discovery data-independent acquisition mass spectrometry (DIA-MS). The identified differentially expressed platelet-associated proteins, were prioritized using ClariaIQ , a proprietary computational platform that ranks proteins based on their relevance to stage-specific oncogenic pathways and established Cancer Hallmarks, to identify stage- and grade-associated proteomic signatures and create the HeLP panel. Results: DIA-MS identified multiple platelet sequestered proteins that were differentially expressed between indolent disease and invasive BC. ClariaIQ prioritization resulted in the selection of 13 proteins for inclusion in the HeLP breast cancer assay. We present two examples: SAA1 and SERPIN proteins demonstrated differential expression between healthy, benign breast lesions and malignant invasive disease (Table 1). SAA1 peaks in early BC and SERPIN in advanced stages. With SAA1, in HER negative BC the levels rise to an average of 285,000 RE units when compared to HER2 positive BC. Conclusions: Platelet sequestered protein signatures provide clinically relevant information regarding breast cancer status, grade, and invasiveness. The findings support the robustness of the signal, and a more patient-specific signature than traditional plasma or serum biomarkers. It suggests a role for HeLP as a minimally invasive adjunct to mammography to improve diagnostic stratification and therapeutic decision-making. Disease Group SAA1 Mean (RE) SAA1 SD (RE) SERPIN A3 Mean (RE) SERPIN A3 SD (RE) Healthy Controls 119,592 206,349 490,231 279,017 Benign Breast Lesions 622,187 50,855 341,102 153,144 Stage I Breast Cancer 1,223,865 1,878,654 742,409 466,468 Stage II Breast Cancer 663,369 1,970,265 922,381 844,512 Stage III Breast Cancer 437,853 662,211 705,994 597,399 Stage IV Breast Cancer 225,265 384,826 1,068,874 1,415,934 RE=Relative Expression units. N=20 subjects included in each group.

7094 Background: Waldenström Macroglobulinemia (WM) remains incurable with current available therapeutic options. Treatment options for relapsed/refractory pts are limited and often continuous, underscoring the need for new agents with novel mechanisms of action and pt-centered, fixed duration therapy. Iopofosine I 131 is a novel radiopharmaceutical compound composed of a lipid raft-targeting phospholipid ether covalently bound to 131 I, a beta emitting radioisotope. Here, we report preliminary sub-group results of the CLOVER-WaM study [NCT02952508] in WM pts treated with a Bruton’s Tyrosine Kinase inhibitor (BTKi) immediately prior to iopofosine. Methods: Eligible WM pts had received >2 prior therapies and had symptomatic disease requiring therapy according to consensus recommendations for WM. Treatment consisted of 2 cycles of iopofosine I 131 administered at 15 mCi/m 2 on days 1 and 15 of each 57-day cycle. The primary efficacy endpoint was major response rate (MRR; partial response or better, as determined by the modified IWWM-VI). Secondary and exploratory endpoints included overall response rate (ORR), treatment-free survival (TFS), progression free survival (PFS), duration of response (DOR), and clinical benefit rate (CBR; stable disease or better). Herein, efficacy endpoints were assessed in the modified intent-to-treat (mITT) population (all pts who received ≥60 mCi total administered dose of iopofosine I 131), and whose treatment regimen prior to iopofosine included a BTKi. Safety was evaluated using CTCAE v4.03 in pts who received ≥1 dose of iopofosine. Data cut off for this analysis was Jan. 16, 2026. Results: As previously reported, 65 pts were dosed and 55 are included in the mITT population. Of those, 22 (40%) had received a BTKi containing regimen immediately prior to iopofosine; and 11 who previously received at least 2 regimens utilizing BTKis and 12 who were refractory to rituximab. In this subgroup, median age was 70.5 (range 55-88), 17 (77%) were male, and 5 (23%) were female. The median number of prior therapies was 3 (range 2-7), 15/22 (68%) were MYD88 mutated and 18/22 (82%) were TP53 wildtype. The MRR was 15/22 (68.2%), ORR was 19/22 (86.4%) and CBR was 100%, median PFS was 12 months (range 1.6 to 28.0) and median TFS was 19.1 months (range 2.5-34.4). Grade ≥ 3, related treatment emergent adverse events (TEAE) occurring in > 10% of pts included anemia (41%), leukopenia (41%), neutropenia (58%), and thrombocytopenia (86%). Conclusions: Iopofosine I 131 demonstrated significant efficacy; 100% CBR, 86.4% ORR and 68.2% MRR with a median PFS of 12 months (range: 1.6 – 28.0 months) in a pt population with no current standard of care therapy. The treatment was well-tolerated with a manageable toxicity profile with cytopenias as the only Grade 3 or greater TEAE. Based on the results of this pivotal trial, iopofosine I 131 could be a promising novel treatment for WM pts after BTKi therapy. Clinical trial information: NCT02952508 .

4178 Background: In the CABINET trial, CABO significantly prolonged progression-free survival (PFS) compared to placebo (PB) in patients (pts) with advanced, previously treated extrapancreatic NET (epNET) or pancreatic NET (pNET) (Chan et al., NEJM, 2025). Here we report outcomes according to functional status based on NET hormone secretion. Methods: Pts with locally advanced or metastatic epNET or pNET were randomized 2:1 in separate cohorts to receive CABO 60 mg daily vs PB. Eligibility included progression by RECIST within 12 months (mo) before registration, ≥ 1 prior systemic therapy not including somatostatin analogs (SSA). Pts with functional NET due to hormone secretion and non-functional NET were included. In this post hoc subgroup analysis, we analyzed PFS by blinded independent central review and adverse events for pts receiving CABO vs PB based on functional status. Cox regression models were used with stratification on primary tumor site (epNET vs pNET). Subset analyses to evaluate treatment arm differences were conducted in pts with functional and non-functional tumors. Due to small numbers, separate results for those with unknown functional status are not included. Results: Of the total 298 pts enrolled in both cohorts, 74 had a functional NET (CABO, n = 47; PB, n = 27); 179 had a non-functional NET (CABO, n = 123; PB, n = 56); 45 had unknown functional status (CABO, n = 28; PB, n = 17). For functional NET, primary tumor sites were GI tract (n = 50; 68%), pancreas (n = 15; 20%), unknown (n = 4; 5%), lung (n = 3; 4%), and thymus (n = 2; 3%). Secreted hormones that were reported included serotonin (55%), somatostatin (18%), gastrin (16%), glucagon (4%), insulin (4%), ACTH (1%), and vasoactive intestinal peptide (1%). For non-functional NET, primary tumor sites were pancreas (n = 75; 42%), GI tract (n = 42; 23%), lung (n = 30; 17%), unknown (n = 17; 9%), thymus (n = 8; 4%), and other (n = 7; 4%). Concurrent SSA was received by 91% and 53% of pts with functional and non-functional NET, respectively. In both subgroups, CABO was associated with improved PFS compared to PB (for functional NET: stratified hazard ratio [sHR], 0.40; 95% confidence interval [CI]: 0.20-0.82, P = 0.012; for non-functional NET: sHR, 0.26; 95% CI: 0.17-0.41, P < 0.001). The most frequent grade 3/4 adverse events (AEs) attributed to CABO vs PB in pts with functional NET included hypertension (21% vs 11%), diarrhea (9% vs 11%), and fatigue (2% vs 15%); in pts with non-functional NET, grade 3/4 AEs included hypertension (21% vs 4%) and fatigue (18% vs 4%). Conclusions: Subset analyses of the CABINET trial suggest that CABO is an effective treatment option for pts with functional and non-functional epNET or pNET. Efficacy and safety results for pts with functional or non-functional NET treated with CABO are consistent with results for the entire trial. Clinical trial information: NCT03375320 .

4163 Background: Standard first-line systemic therapy for hepatocellular carcinoma involves immune checkpoint inhibitors, including A+B and the STRIDE regimen consisting of D+T. However, there is limited data comparing outcomes of patients receiving these two regimens. We aimed to compare the survival and safety profiles of patients receiving A+B versus D+T as first-line systemic therapy for advanced HCC in a propensity score matched analysis. Methods: We performed a retrospective cohort study using data from TriNetX, a healthcare database of over 150 million patients in the United States. We identified adult patients with a history of HCC and included those who received A+B or D+T as first line treatment. Propensity score matching (PSM) was conducted, matching for patient demographics (age, sex, race), clinical history (alcohol use, ascites, esophageal varices, viral hepatitis), and laboratory parameters [platelets, albumin, bilirubin, INR, alpha-1-fetoprotein (AFP)]. Median overall survival (mOS) and relevant patient safety events were compared between those who received A+B or D+T. Results: We identified 2,762 patients who had HCC who were treated with A+B or D+T, of which 2,030 patients received A+B and 723 patients received D+T. Compared to patients in the A+B cohort, those who received D+T were more often older (68.5 vs 66.9 years, standardized mean difference (SMD) = 0.17), had lower platelet counts (186.4 vs 198.6, SMD = 0.11), had higher prevalence of ascites (33.1% vs 20.3%, SMD = 0.29), and alcohol use (23.8% vs 18.8%, SMD = 0.12). After PSM, 723 patients were included in survival analyses, with all variables adequately balanced except for albumin, which was higher in the A+B group (3.6 vs 3.5, SMD = 0.19). At 90 days after starting therapy, D+T was associated with higher incidence of immune-mediated colitis [5.3% vs 2.6%, odds ratio (OR) 2.1; 95% confidence interval (CI), 1.2-3.7], and a higher risk of hospitalization [35.4% vs 27.9%, OR 1.4; 95% CI, 1.1-1.8]. At 6 months, the risk of hypertension and proteinuria was higher in the A+B cohort [21.9% vs 13.7%, OR 0.57; 95% CI, 0.34-0.95], which persisted at 1 year [28.1% vs 16.5%, OR 0.51; 95% CI, 0.32-0.81]. There was no significant difference in mOS between those receiving A+B or D+T [18.3 months vs 22.8 months, hazard ratio (HR) 0.94; 95% CI, 0.79-1.1]. Conclusions: In patients with advanced HCC who received A+B or D+T as first-line systemic therapy, we found that A+B was associated with higher risk of hypertension and proteinuria, while D+T was associated with a higher risk of immune-mediated colitis and hospitalization. No significant difference in mOS was observed between the cohorts. These findings suggest that safety profiles, rather than survival differences, may be used to guide optimal first-line treatment regimens. Prospective studies are warranted to further assess differences in patient outcomes.

4157 Background: IDH1/2 mutations occur in ~25% of cholangiocarcinomas (CCAs). Preclinical studies suggest synergy between PARP inhibition and PD-L1 blockade. We previously conducted a phase II trial of olaparib plus durvalumab in advanced IDH -mutant CCA. We report matched baseline tissue and serial cell-free DNA (cfDNA)-based correlative analysis of pts samples. The primary objective was to develop a cfDNA methylome signature as a non-invasive biomarker. Methods: This single-arm, open-label phase II study (NCT03991832) enrolled patients with unresectable/metastatic IDH -mutant CCA and ≤2 prior lines of systemic therapy. Patients received olaparib 300 mg orally twice daily and durvalumab 1500 mg IV every 4 weeks. Blood samples were collected at baseline and monthly while on treatment for planned correlatives to examine R2HG, S2HG, and artemin levels using HPLC (High-Performance Liquid Chromatography). Cell-free methylated DNA immunoprecipitation and high-throughput sequencing (cfMeDIP-seq) was performed on pts cfDNA samples and case-matched IDH -wildtype pts. Formalin-fixed, paraffin-embedded blocks of baseline tumor biopsies were used for multispectral fluorescent IHC (FL-IHC) using a 6-marker panel composed of pan-cytokeratin, CD4, CD8, CD163, PD-L1, and CD68. Results: Ten patients were enrolled (median age 63.5 y; 50% female; 90% received prior platinum). Median treatment duration was 1.95 mo (range 1.8–13.5). No complete or partial responses were observed. DCR was 30% (3 patients with stable disease); one patient remained on therapy for 13.5 mo before progression. Median PFS was 1.97 mo (95% CI 1.73–3.93). HPLC from baseline plasma showed lower baseline artemin levels correlated with stable disease (p=0.038), while R2HG/S2HG ratios showed no association with outcome. FL-IHC showed enriched immune cell populations, specifically CD4 + T cells (p=0.0032) and a trend for CD68 + macrophages (p=0.062), in the tumor stroma compared with tumor core. 54 plasma samples (from 8 patients) were profiled with cfMeDIP-seq along with 8 IDH -wildtype controls. Using top 100 differentially methylated regions, the circulating tumour DNA methylome exhibited a highly specific signature, accurately discriminating IDH -mutant and IDH -wildtype CCA regardless of treatment status. The specific differentially methylated gene pathways between groups were comprehensively examined in both on-treatment and baseline plasma samples. Conclusions: Advanced IDH -mutant CCA harbors an immune-excluded phenotype, which may underlie primary resistance to immunotherapy. Plasma cfDNA methylome signature can accurately discriminate CCA with IDH mutations. Clinical trial information: NCT03991832 .

2016 Background: Bevacizumab therapy (Bev) for recurrent glioblastoma (rGBM) has not demonstrated improved overall survival (OS) in randomized clinical trials. However, single-center and preliminary multi-center studies suggest that relative cerebral blood volume (rCBV) measured with dynamic susceptibility contrast MRI (DSC-MRI) at baseline or shortly after treatment initiation may predict response to Bev. The primary aim of ECOG-ACRIN EAF151 was to evaluate whether early binary change in rCBV, assessed 2–3 weeks after initiation of Bev-containing therapy, identifies patients with an OS benefit of ≥4 mos. Pre-specified secondary aims assessed baseline rCBV; post-hoc exploratory analyses examined early post-Rx rCBV. Methods: A prospective, phase II multi-center trial without randomization enrolled subjects with rGBM receiving their first Bev-containing therapy. Progression was determined by local sites (RANO criteria; MRI within 28 days of registration, ≥42 days since end of chemoradiation). Baseline (S0) and follow-up (S1) DSC-MRI were performed before the first Bev infusion (within 3 days), and 12-25 days post-infusion but before the second infusion. Anatomic MRI and DSC-MRI (double-dose Gadavist injection, full-dose preload) complied with recommended protocols. Mean normalized (nRCBV) and standardized (sRCBV) rCBV were extracted from contrast-enhancing tumor ROIs. A 2-sided logrank test (α=0.1) was used to test the primary aim (change in mean nRCBV from S0 to S1, ≥0 vs. <0). Cox regression with restricted cubic splines was used to assess the association between continuous rCBV markers and OS. Results: 146 subjects were accrued from 33 sites. 134 completed S0 and 118 completed both S0 and S1. After exclusion of uninterpretable scans, 107 were evaluable for change in rCBV, and 124 for baseline rCBV. There was no statistically significant difference in OS between subjects with binary increase (n=40; median OS 8.0 mos [90% CI 5.5–9.2]) vs. decrease (n=67; 7.9 mos [90% CI 6.3–10.3]) in mean nRCBV (p=0.67). Based on the spline fits, we observed a strong nonlinear association between OS and continuous nRCBV and sRCBV at both S0 and S1: low marker values are associated with lower risk, but beyond a threshold, higher values are not associated with greater risk. As an exploratory analysis, we estimated optimal cut points (nRCBV: S0=1.11, S1=1.16; sRCBV: S0=1.13, S1=0.99) and found that subjects whose S1 rCBV decreased below threshold had a median OS 2.7 mos (nRCBV, HR 0.61 [90% CI 0.41–0.88]) and 5.2 mos (sRCBV, HR 0.43 [90% CI 0.28–0.63]) longer than subjects whose rCBV either increased or did not decrease below threshold. Conclusions: EAF151 prospectively evaluated whether DSC-MRI markers predict OS in patients with rGBM treated with Bev. Although the change in these markers was not predictive, both baseline and early post-Rx markers were predictive of OS. Clinical trial information: NCT03115333 .

12010 Background: BWEL (Alliance A011401; NCT02750826) is a Phase III trial that randomizes patients (pts) with stage II-III breast cancer and body mass index (BMI) ≥27 kg/m 2 1:1 to a 24-month (mo) lifestyle-based WLI + health education (HE) or HE alone. Here we report prespecified secondary outcomes of the impact of the WLI on patient-reported QOL and symptoms. Methods: The first 540 BWEL pts (randomized between 9/2016 and 7/2017) were included in this substudy that collected PROMIS 29 Profile 2.0 and Global Health scores at enrollment, 6 and 24 mos. Adjusting for baseline scores, mean physical function (predefined substudy primary outcome), global physical and mental health, fatigue and other scores were compared at 6 and 24 mos using analysis of covariance (ANCOVA). P-values <0.05 were considered significant. Positive differences in positive attributes (e.g., physical function) and negative differences in negative attributes (e.g., anxiety) represented better outcomes in the WLI arm. Results: At baseline, median BMI was 32.9 kg/m 2 (26.5 – 69.1), median age was 53 (25 - 78) years; 83.9% of pts were non-Hispanic White, 10.7% were Black and 5.9% were Hispanic. At 6 mos, the WLI (vs HE) arm had significantly better physical function (ANCOVA-based mean difference between arms 1.9 [95% CI 0.8, 3.0]; p<0.001), global physical health (2.0 [95% CI 0.9, 3.0]; p<0.001), global mental health (1.30 [95% CI 0.2, 2.4], p=0.03), social roles and activities (2.3 [95% CI 1.1, 3.6]; p<0.001), and fatigue (-1.7 [95% CI -3.1, -0.4], p=0.01) (Table). Improvements were generally maintained at 24 mos. Similar findings were seen in analyses using longitudinal mixed modeling. Conclusions: The BWEL WLI demonstrated QOL benefits for patients with breast cancer, resulting in significantly better physical function, global physical and mental health, and symptoms. Future analyses will evaluate which populations experienced the most benefit, as well as the relationships among QOL, symptoms, and weight loss. Support: U10CA180821, U10CA180882, UG1CA189823; U10CA180820; U10CA180868; U10CA180863, CCS 707213; U10CA180888; UG1CA189858; https://acknowledgments.alliancefound.org. Clinical trial information: NCT02750826 . Analysis of covariance-adjusted least squares means values at 6-mos adjusted for baseline scores. QOL/Symptom Attributes HE WLI Between arm difference (95% CI)* P value Physical Function 47.1 49.0 1.9 (0.8, 3.0) <0.001 Global Physical Health 46.2 48.1 2.0 (0.9, 3.0) <0.001 Global Mental Health 48.6 49.9 1.3 (0.2, 2.4) 0.03 Social Roles and Activities 52.7 55.0 2.3 (1.1, 3.6) <0.001 Anxiety 50.2 50.0 -0.2 (-1.6, 1.2) 0.77 Depression 47.5 47.5 -0.0 (11.2, 1.2) 0.96 Fatigue 50.6 48.9 -1.7 (-3.1, -0.4) 0.01 Sleep Disturbance 51.0 51.1 0.1 (-0.6, 0.8) 0.80 Pain Interference 51.3 50.3 -1.0 (-2.4, 0.4) 0.15 *Positive differences in positive attributes and negative differences in negative attributes favor WLI arm.