Buckner, Jan C.

9563 Background: Fatigue is a prevalent and debilitating symptom reported by cancer patients (pts) which compromises a pt's quality of life (QOL). This study examined the relationship between PR fatigue and QOL as well as cancer-related symptoms (CRS) in 43 North Central Cancer Treatment Group and Mayo Clinic Cancer Center clinical trials. Methods: 3,915 pts from 43 oncology clinical trials provided baseline fatigue data on a single-item 0–100 point scale. Pts' QOL assessment included a single-item overall QOL and associated QOL domains measured by numerical analogues, the Profile of Mood States (POMS), and PR symptom assessment measures. Associations between fatigue and QOL domains were assessed by Spearman correlation coefficients. Wilcoxon rank sum test compared QOL scores between pts with clinically deficient fatigue(CDF, score ≤50) vs. no clinically deficient fatigue (nCDF, score>50). Changes from baseline in fatigue and QOL were compared by Wilcoxon rank sum test with a 20-point change defined as clinically meaningful. Results: 38% of pts reported CDF at baseline and 45% of pts reported CDF at last assessment. Fatigue was only moderately correlated at best with overall QOL, pain, POMS, social and physical function (Spearman rho's of .27,.40, .56, .38 and .38 respectively). Pts with CDF averaged over 10 points lower overall QOL, pain, POMS, social, and physical function (see table below, all p<.0001) as well as worsening CRS including sleepiness, nausea, headache, abnormal sweating, trouble sleeping, dry mouth, and sexual dysfunction (all p<.001). Pts with 20+ points worsening in fatigue declined in overall QOL, physical function, pain and POMS (all p<.0001). Conclusions: Patients with CDF suffer greater deficits in QOL and CRS. Patients report fatigue as distinctly different from overall QOL, pain, physical, social, mood status and CRS. Fatigue appears with a broad spectrum of CRS clusters. Routine measurement and management of fatigue could impact QOL and treatment-related symptoms. [Table: see text] No significant financial relationships to disclose.

e20519 Background: Radiation Therapy Oncology Group 9402 compared PCV chemotherapy plus radiation therapy (PCV+RT) versus RT alone for anaplastic oligodendroglioma. Here we report 1) longitudinal changes in cognition and quality of life, 2) effects of patient factors and treatments on cognition, quality of life and survival, and 3) prognostic implications of cognition and quality of life. Methods: Cognition was assessed by Mini Mental Status Examination (MMSE) and quality of life by Brain-Quality of Life (B-QOL) by repeat assessments. Scores were analyzed for survivors and within five years of death. Shared parameter models evaluated MMSE/B-QOL with survival. Results: For survivors, MMSE and B-QOL scores were similar longitudinally and between treatments. For those dying within 5 years, MMSE scores were stable initially, while B-QOL scores decreased; both declined rapidly in the last year of life and similarly between arms. In the aggregate, scores decreased over time (P=0.0413 for MMSE; P=0.0016 for B-QOL) and were superior with age < 50 years (P<0.001 for MMSE; P=0.0554 for B-QOL) and KPS 80–100 (P<0.001). Younger age and higher KPS were associated with longer survival. After adjusting for patient factors and drop-out, survival was longer after PCV+RT (HR=0.66, 95% CI=0.49–0.9, P=0.0084; HR=0.74, 95% CI=0.54–1.01, P=0.0592) in models with MMSE and B-QOL. There were no differences in MMSE and B-QOL scores between arms (P=0.4752 and P=0.2767, respectively); higher scores predicted longer survival. Conclusions: MMSE and B-QOL scores held steady in both arms for survivors. For those who died, B-QOL scores declined slowly until the last year of life, then rapidly. Younger, fitter patients had better MMSE and B-QOL scores and longer survival. No significant financial relationships to disclose.

2019 Background: The mammalian target of rapamycin (mTOR) functions within the PI3K/Akt signaling pathway as a critical modulator of cell survival. We previously demonstrated significant synergy of the mTOR inhibitor sirolimus with RT in glioma xenografts. Methods: The standard cohorts of 3 design was applied with dose escalation of weekly IV CCI-779 in combination with standard TMZ/RT. CCI-779 was given during both RT (60 Gy)/TMZ (75 mg/m2 daily) and adjuvant TMZ (200 mg/m2 daily x 5 every 28 days). Results: A total of 17 patients were enrolled. CCI-779 therapy during RT/TMZ was well tolerated at dose level 0 (25 mg CCI-779, n = 3) and dose level 1 (50 mg CCI-779, n = 6) with 1 of 9 patients experiencing a DLT (Gr 3 fatigue). Dose level 2 (75 mg CCI-779) exceeded the maximally tolerated dose with two of six patients with DLT (<75% CCI-779 delivered; Gr 4 dyspnea). Despite reasonable tolerance during RT/TMZ, the overall regimen was associated with a high rate of infection associated with lymphopenia. After a patient died from PCP on cycle 2 of adjuvant TMZ/CCI-779, antibiotic prophylaxis was mandated. Two other patients died of gram-negative sepsis despite prophylaxis: one after their first dose of CCI-779 and one during cycle 4 of adjuvant therapy. In contrast to our 18% grade 5 infection rate, only 4% grade 3 (no grade 4/5) infections were observed in 26 other CTEP-sponsored clinical trials involving 1,006 patients treated with CCI-779. Results from translational studies evaluating the effects of treatment on immune function will be presented. Further infections were avoided on this trial after CCI-779 therapy was limited to RT/TMZ. Conclusions: Although CCI-779 in combination with RT/TMZ was well-tolerated, adjuvant therapy with TMZ/CCI-779 was associated with an increased risk of opportunistic infections. [Table: see text]

PURPOSENRG Oncology/RTOG 9802 (ClinicalTrials.gov Identifier: NCT00003375 ) is a practice-changing study for patients with WHO low-grade glioma (LGG, grade II), as it was the first to demonstrate a survival benefit of adjuvant chemoradiotherapy over radiotherapy. This post hoc study sought to determine the prognostic and predictive impact of the WHO-defined molecular subgroups and corresponding molecular alterations within NRG Oncology/RTOG 9802.METHODSIDH1/2 mutations were determined by immunohistochemistry and/or deep sequencing. A custom Ion AmpliSeq panel was used for mutation analysis. 1p/19q codeletion and MGMT promoter methylation were determined by copy-number arrays and/or Illumina 450K array, respectively. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Hazard ratios (HRs) were calculated using the Cox proportional hazard model and tested using the log-rank test. Multivariable analyses (MVAs) were performed incorporating treatment and common prognostic factors as covariates.RESULTSOf the eligible patients successfully profiled for the WHO-defined molecular groups (n = 106/251), 26 (24%) were IDH-wild type, 43 (41%) were IDH-mutant/non-codeleted, and 37(35%) were IDH-mutant/codeleted. MVAs demonstrated that WHO subgroup was a significant predictor of PFS after adjustment for clinical variables and treatment. Notably, treatment with postradiation chemotherapy (PCV; procarbazine, lomustine (CCNU), and vincristine) was associated with longer PFS (HR, 0.32; P = .003; HR, 0.13; P < .001) and OS (HR, 0.38; P = .013; HR, 0.21; P = .029) in the IDH-mutant/non-codeleted and IDH-mutant/codeleted subgroups, respectively. In contrast, no significant difference in either PFS or OS was observed with the addition of PCV in the IDH-wild-type subgroup.CONCLUSIONThis study is the first to report the predictive value of the WHO-defined diagnostic classification in a set of uniformly treated patients with LGG in a clinical trial. Importantly, this post hoc analysis supports the notion that patients with IDH-mutant high-risk LGG regardless of codeletion status receive benefit from the addition of PCV.

e24176 Background: Decision aids for prostate cancer treatment can improve knowledge, but the relative effect of pre-consultation and within-consultation DAs is not known. Methods: We conducted a parallel design, 2-by-2 factorial, 4-arm, cluster-RCT in urology practices affiliated with the NCI’s Alliance research base. We compared patient knowledge immediately after consultation (%12-item% correct) intervention arms compared to usual care. We used mixed effects regression modeling to assess effect of interventions on knowledge adjusting for site-clustering, race/ethnicity (non-Hispanic White; Other), age (years), clinical stage (T1-3), PSA, and Gleason score. Results: 15 of 21 randomized centers accrued 158 pts from Nov 2017 to June 2019. The arm delivering both DAs (n = 3 sites) recruited 25 pts. The pre-consultation DA arm (n = 4 sites) recruited 39 pts. The within-consultation DA arm (n = 4 sites) recruited 44 pts. The no DA arm (n = 4 sites) accrued 50 pts. Overall, mean age was 64; 54% were AA; 73% had T1 stage; median Gleason = 7; and median PSA = 7. The combined DAs group, followed by pre-consultation reported higher median knowledge (75% and 67%, respectively). The within-consultation and no DA arms both reported median knowledge scores (58%). Within arm, inter-site standard deviations in mean knowledge scores ranged from 0.164 in in the pre-consultation arm to 0.232 in the usual care arm. Neither pre-consultation nor within-consultation DAs had statistically significant effects (p = .15 and p = .99, respectively). Pre-specified adjusted difference [97.5% CIs], comparing the pre-consultation DA and the within-consultation DA with the control was 9.4% [-7.3%, 26.2%] and -0.4% [-16.9%, 16.1%], respectively. Intra-cluster correlation (ICC) coefficient was high (.24). No interaction effects were identified (p = .98). A post-hoc analysis comparing any DA vs usual care found a mean adjusted difference [95% CI] of 5.6% [-8.5%, 19.8%] (p = 0.40), 63.9% for any DA and 58.3% for usual care. Conclusions: Possible knowledge gains associated with some DAs for early prostate cancer were obscured by larger-than-expected intra-cluster correlation effects associated with the primary outcome. How interventions were used was not measured. Support:UG1CA189823; https://acknowledgments.alliancefound.org ; R01 MD008934-06. Clinical trial information: NCT03103321 .

8583 Background: Patient QOL assessment requires balancing the detail provided by multi-item assessments with the reduced burden of single-item assessments. We investigated the psychometric properties of single-item LASA assessments used in 3 North Central Cancer Treatment Group (NCCTG) phase II trials for patients with newly diagnosed high-grade gliomas. Methods: Measures included QOL LASAs (overall, physical, emotional, spiritual, intellectual), Symptom Distress Scale (SDS), Profile of Mood States (POMS), and Functional Assessment for Cancer Therapy (FACT; overall, physical, emotional). Association of LASA measures with SDS, POMS, and FACT domains and with ECOG performance score (PS) and MMSE was assessed with Spearman’s correlation. Repeated measures ANOVA models compared the change over time of LASAs and SDS, POMS, and FACT. Cox regression modeled the association of baseline QOL and survival. Results: 205 patients completed the QOL assessments across 3 time points. LASA mean scores ranged from 60–78; SDS, POMS, and FACT ranged from 68–81. No significant changes across time for overall and emotional scores were observed. FACT physical decreased over time (p<0.001) as did LASA physical (p=0.08). LASA scales were strongly associated with corresponding scales on SDS, POMS, and FACT (0.44<rho<0.65; p<0.001). LASA was negatively associated with PS and positively with MMSE. Baseline scores for overall FACT (p=0.005) and LASA physical (p=0.015) were associated with better survival. Conclusions: The single-item LASA assessments have comparable psychometric properties as longer assessments for the same constructs. Correlations with PS and MMSE were as expected (convergent/concurrent validity). The discriminant validity and prognostic ability of LASA items were similar to the multi-item instruments. Collectively, the data suggest that the single item LASA scales are valid for assessing QOL in patients with newly diagnosed high grade gliomas and are an appropriate alternative when a shorter instrument is warranted. No significant financial relationships to disclose.

8527 Background: Minority patients (MP) suffer deficits in access to care and socioeconomic status. This study uses a patient-level pooled analysis to explore whether these deficits translate into quality of life (QOL) differences between MP and non-MP on clinical trials. Method: Baseline QOL scores were combined from 47 clinical trials (6,513 patients) conducted either at the Mayo Clinic Cancer Center or in the North Central Cancer Treatment Group. QOL scales used were the Uniscale, Linear Analogue Self Assessment (LASA), Symptom Distress Scale (SDS), Profile of Mood States (POMS) and Functional Assessment of Cancer Therapy - General (Fact-G). Fisher’s Exact tests and linear regression adjusted for age, site, and performance score. Survival data was compared using the method of Kaplan-Meier. Results: Eight percent (531) of patients self-reported as MP (0.45% American Indian/Alaskan Native, 0.7% Asian, 5% Black/African American, 1.5% Hispanic, 0.1% Native Hawaiian and 0.3% Other). MP had no meaningful deficits in overall QOL or the SDS and were slightly worse on FACT-G total score, physical, social/family, functional, and SDS nausea severity. MP among lung cancer patients reported greater nausea (58 vs 69) and sleep problems (34 vs 54), with neurological cancers reported worse emotional well-being (53 vs 74), and with GI tumors had lower social/family well-being (60 vs 67). Regression models confirmed these results. Median survival time was shorter for MP (198 vs 310 days, p=0.001) but was not significant after adjusting for disease severity. Conclusions: MP on these clinical trials did not report large QOL deficits at baseline relative to non-MP. MP did indicate small deficits in physical, social, and emotional subscales. MP experienced large tumor-specific deficits for a few QOL domains that might bear further attention. [Table: see text] No significant financial relationships to disclose.

2025 Background: Although adjuvant radiation has demonstrated a clear survival benefit in anaplastic astrocytomas (AA), the role of concurrent temozolomide (TMZ) remains controversial. Methods: All adult patients diagnosed with AA from 2001 to 2011 and treated with standard doses of adjuvant radiation were identified retrospectively using the neuro-oncology database at the Mayo Clinic (Rochester, MN). Clinical data was extracted from the electronic medical record. IDH mutation status was also determined by obtaining either IDH1R132H immunostain on existing unstained slides or paraffin block sections, or by sequencing. Cumulative survival probabilities were estimated using the Kaplan-Meier method. Univariable and multivariable Cox proportional hazards regression models were fit to compare patients who did/did not receive TMZ. Results: 218 patients were identified that met inclusion criteria. 34 patients were excluded due to missing data on adjuvant chemotherapy. 146 patients had received adjuvant TMZ while 38 had not. Of these, IDH mutation status was determined on 124 patients who received TMZ and 33 of those who had not. The median duration of follow up was 36.4 months. On univariable analysis, adjuvant TMZ demonstrated a trend towards improved median survival from 35.2 to 53.1 months (p=0.06). As an independent variable, patients with IDH mutations had longer median survivals (111.7 months) when compared to IDH wild-type patients (23.3 months) (p<0.001). On multivariable analysis, five-year-survival was significantly impacted by receipt of adjuvant TMZ (HR = 0.56, p=0.03) and IDH mutation status remained a significant prognostic factor (HR = 0.19, p < 0.001) (see Table). Conclusions: IDH mutation strongly predicts a favorable outcome in patients with AA. Secondarily, concurrent TMZ is also associated with improved survival in patients with AA who are receiving adjuvant radiotherapy. [Table: see text]

6133 Background: Patient (pt) trial experience may give insight to quality of life (QOL) factors affecting accrual, retention and outcome. While pts are vital to clinical trial success, we know little about their post-trial opinions. This trial examined pt opinion of their trial and treatment decision making (TDM). Methods: Pts enrolled on designated North Central Cancer Treatment Group (NCCTG) phase II or III treatment trials completed the TDM Control Preferences Scale at baseline and the Was It Worth It (WIWI) satisfaction assessment at the ends of cycle 1 and active protocol treatment. The primary endpoint was the proportion of pts reporting worthwhile participation. Fisher Exact tests compared pt opinion across subgroups. Results: As of 01/15/2012, 264 pts were enrolled on 25 protocols and treated at 79 sites. 86% of pts were in phase II studies and 89% had stage IV disease. At the end of cycle 1, pts felt the trial was worthwhile (74%), would do it again (85%), and would recommend it to others (82%). 85% of pts reported undiminished QOL and only 7% rated the trial worse than expected. End of treatment responses were similar. Satisfaction rates varied by tumor site (p=0.04). 11% of pts having tumor response rated the trial as not worthwhile, and 66% of pts with progressive disease rated it worthwhile (see table). Pts with concordant preferred and actual TDM roles rated participation higher than pts with discordant TDM roles (see table). Conclusions: Most pts endorsed their clinical trial experience. Contrary to popular beliefs, treatment outcome did not have an overwhelming impact on pt satisfaction, and was just one of many factors such as TDM role discordance. Assessing pt satisfaction will inform future study design that can potentially improve pt accrual and retention. [Table: see text]