Sloan, Jeff A.

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.

9532 Background: Chemotherapy induced peripheral neuropathy (CIPN) continues to be a substantial problem for many cancer patients (pts). Pursuant to promising appearing pilot data, the current study evaluated the use of vitamin E for the prevention of CIPN. Methods: A phase III, randomized, double-blind, placebo controlled study was conducted in pts undergoing therapy with neurotoxic chemotherapy, utilizing twice daily dosing of vitamin E (400mg)/placebo. The primary endpoint was the incidence of grade 2+ sensory neuropathy (SN) toxicity (CTCAE v 3.0) in each treatment arm, analyzed by Chi-square testing. Major eligibility criteria included: planned curative intent adjuvant chemotherapy with neurotoxic chemotherapy, ≥ 18 years of age, ECOG PS of ≤2, no existing peripheral neuropathy or coronary artery disease, no prior treatment with neurotoxic chemotherapy, and no concurrent treatment with neuropathic or opioid pain medication. Planned sample size was 100 patients per arm, to provide 80% power to detect a difference in incidence of grade 2+ SN toxicity from 25% in the placebo group to 10% in the vitamin E group. Results: Two-hundred seven pts were enrolled between 12/01/2006 and 12/14/2007. Cytotoxic agents included taxanes (109), cisplatin (8), carboplatin (2), oxaliplatin (50) or combination (20). Eleven pts canceled prior to starting treatment and there were 7 ineligible pts on study. Thus there were 189 evaluable pts included in the current analysis. In this analysis, there was no difference in the incidence of grade 2+ SN between the 2 arms (vitamin E- 34% [95% CI- 25.0–44.8%] placebo- 29% [20.1–39.4%]; P=0.43). There, likewise, were no significant differences between treatment arms for time to onset of neuropathy (P= 0.72), for chemotherapy dose reductions due to neuropathy (P= 0.21) or patient questionnaire reported neuropathy symptoms. The treatment was well tolerated overall. Conclusions: Vitamin E did not appear to reduce the incidence of sensory neuropathy in the studied group of patients receiving neurotoxic chemotherapy but it appeared to be well tolerated. No significant financial relationships to disclose.

4025 Background: Cumulative sNT is the dose-limiting toxicity of oxaliplatin which commonly leads to early discontinuation of oxaliplatin-based therapy in the palliative and adjuvant setting. We recently demonstrated the protective effect of CaMg against oxaliplatin-induced sNT as assessed by NCI-CTC (Nikcevich ASCO 2008). It is unclear, though, if CaMg reduced acute and/or chronic, cumulative sNT. Methods: 104 pts with colon cancer undergoing adjuvant therapy with FOLFOX were randomized to IV CaMg (1g calcium gluconate plus 1g magnesium sulfate pre- and post-oxaliplatin) or placebo (PL) in a double-blinded manner. NCI-CTC, an oxaliplatin-specific sNT scale and patient-reported outcome (PRO) questionnaires were used to differentially assess the effect of CaMg on acute (effect on sNT on days 1–4 after oxaliplatin) and chronic sNT (area between curves over whole course of therapy). Results: A total of 102 pts (50 CaMg, 52 PL; 96 mFOLFOX6, 6 FOLFOX4) were available for analysis. Apart from a strong reduction in muscle cramps with CaMg (p=0.002), no difference was found between CaMg and PL in PRO with regard to items reflecting acute sNT (e.g. sensitivity to cold, swallowing of cold liquids, throat discomfort) on days 1–4 after oxaliplatin of any treatment cycle. In contrast, CaMg was able to significantly reduce cumulative sNT in form of numbness in fingers (p=0.02), impaired ability to button shirts (p=0.05), tingling in fingers (p=0.06), and muscle cramps over the course of therapy (p=0.01). Conclusions: In our phase III, placebo-controlled trial, CaMg was able to significantly reduce chronic, cumulative sNT related to oxaliplatin as evaluated by specific PRO questionnaires. No effect was noted on phenomena associated with acute sNT. CaMg can be recommended as neuroprotectant against oxaliplatin-related chronic sNT, oxaliplatin's dose-limiting toxicity. [Table: see text]

Approximately 350,000 ventral hernia repairs are performed in the United States each year. Patients expect fast recovery after laparoscopic ventral hernia repair (LVHR) and undisturbed postoperative quality of life (QOL). We examined the utility of a brief, validated 10-point Linear Analog Self-Assessment coupled with the Visual Analog Scale pain scale to discern risk factors for decreased postoperative QOL. Between January 2011 and May 2013, we prospectively assessed patient-reported outcomes for patients who underwent LVHR. Visual Analog Scale pain scale and Linear Analog Self-Assessment items were recorded preoperatively and postoperatively at four hours, one day, and seven days. Eighteen patients were included, 11 were female (61%) and 8 > 60 years old (44%). Patient-reported fatigue increased clinically and statistically from baseline over time ( P = 0.007) as did pain ( P < 0.001). There was a statistically significant difference in QOL scores over time by gender with women reporting worse scores than men ( P = 0.001). In conclusion, our study detected significant changes from baseline in both fatigue and pain over the seven days after LVHR. Age is associated with postoperative differences in physical well-being. Gender is associated with differences in postoperative course in QOL and physical well-being.

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 .

12007 Background: Up to 96% of patients with high grade glioma (HGG) report moderate to severe fatigue. Armodafinil, the R-enantiomer of modafinil, is a psychostimulant with low potential for abuse that has shown potential for improving severe fatigue in HGG patients. Methods: In this phase III double blinded placebo-controlled study, adults with HGG and moderate to severe fatigue, > 4 weeks after completing radiotherapy, were randomized to receive armodafinil daily (150 mg or 250 mg) or placebo for a total of 8 weeks. The primary outcome was efficacy in treating severe fatigue. Secondary outcomes included evaluation of tolerability, neurocognitive function, and quality of life. Patients were evaluated at baseline, 4 and 8 weeks. Results: A total of 328 patients were enrolled between 6/3/13-3/1/19. There were 103 (150 mg arm), 97 (250 mg arm) and 97 (placebo arm) evaluable patients with primary endpoint data available. The median age was 60 years (20-85) with a median Brief Fatigue Inventory (BFI) worst fatigue score of 8 (6-10). 60.3% were male, 80.5% received concomitant chemotherapy, and 39.7% were on corticosteroids. The global fatigue score at end of weeks 4 and 8 were lower than at baseline (p<0.0001) and in the 250 mg arm than placebo (p=0.0356) and was higher for corticosteroid users than non-users (p=0.0002). There was no statistically significant difference for clinically meaningful improvement in BFI usual fatigue score from baseline to end of week 8 between the three arms (p=0.9601). Patients reported an improvement in concentration at week 4 from baseline on the 150 mg arm(P=0.0311). There was no statistically significant difference on neurocognitive tests from baseline to end of week 4 (p>0.05) or week 8 (p>0.05) between arms. More patients reported insomnia on the 250 mg arm (p=0.0083). Conclusions: There is no meaningful benefit of the use of armodafinil to reduce moderate to severe fatigue in patients with HGG. In certain cases there may be benefit of armodafinil 150 mg to aid concentration without the risk of insomnia.Support: UG1CA189823;U10CA180868 (NRG). Clinical trial information: NCT01781468 .

7018 Background: Standard reporting of symptomatic adverse events (AEs) in oncology relies on clinicians to rate patient (pt) experience using CTCAE; each symptom is represented by a single graded item. To capture direct pt experience, NCI developed PRO-CTCAE to supplement CTCAE. In PRO-CTCAE, the pt answers up to 3 questions per AE about a symptom’s frequency, severity and interference with daily activities. To align PRO-CTCAE with CTCAE, we developed an algorithm for mapping sets of questions for an AE to a single composite numerical grade. Methods: We used a 5-step process. (1) All 187 possible PRO-CTCAE score permutations were presented to clinical investigators to subjectively map permutations to single numerical grades (range 0-3). (2) Permutations with < 75% agreement were presented to investigator committees at a National Clinical Trials Network meeting to gain majority consensus via anonymous voting. (3) The resulting algorithm was refined via graphical and tabular approaches to assure directional consistency. (4) Validity, reliability and sensitivity were assessed in a national study dataset. (5) Accuracy for delineating AEs between study arms was measured in 2 phase III clinical trials (Alliance for Clinical Trials in Oncology A091105 and Exelixis COMET-2). Results: (1) 12/187 score permutations had < 75% initial agreement. (2) Majority consensus was reached for all permutations. (3) 5 mappings were adjusted to assure directional consistency. (4) Composite grades for 46/59 (78%) AEs were higher in pts with ECOG performance status 2-4 vs 0-1 (median effect size 0.23 [range -0.49-0.73]; 32/59 effect size ≥0.2; 25/59 p< 0.05), similar to when conducting analysis on individual unmapped items. The test-retest reliability for 24 selected composite grades ranged from 0.57-0.96 (median intraclass correlation coefficient [ICC] 0.77) with 18/24 (75%) grades having ICC ≥0.7. Median (range) standardized response means in pts reporting worsening, no change, and improvement were 0.20 (0.03-0.34), -0.06 (-0.20-0.03) and -0.12 (-0.32-0.06). (5) Pattern, directionality and statistical significance of between-arm differences in both trials were preserved with composite grades as compared to individual unmapped items. Conclusions: A composite grading algorithm for PRO-CTCAE was rigorously developed and validated. PRO-CTCAE composite grades may be useful in analyses to provide a single metric for each pt-reported AE for trial and real-world reporting. Support: UG1CA189823; U01CA233046; HHSN261200800043C; Bayer (A091105); https://acknowledgments.alliancefound.org .

Abstract Background: Current dogma for the management of patients with PV dictates controlling erythrocytosis (to goal hematocrit levels of &lt;45% (males) or &lt;42%(females)) to decrease risks of thrombohemorrhagic complications. Control is achieved by either phlebotomy (through induction of iatrogenic iron deficiency), and/or direct myelosuppression (through hydroxyurea, interferon-alpha, or anagrelide). Although phlebotomy is clinically considered a very benign therapy, we hypothesize that PV associated fatigue is exacerbated by iron deficiency induced fatigue (Qual Life Res2000;9:5(491–7)), and evaluated the impact of therapeutic control of erythrocytosis on PV patients. Methods: A detailed analysis of patients with PV whom responded to an international web based survey of MPD patients which registered responses regarding diagnosis, disease course, current medications, current blood counts, frequency of phlebotomy, constitutional symptoms, and fatigue (FACT-An and Brief Fatigue Inventory). Results: A total of 405 self reported PV patients (median age 56; 48% female) from a wide geographic international distribution responded. Individuals were a median of 4 years from their initial diagnosis of PV (range 0–36). Prior PV associated complications were reported as thrombotic (n=98; 24%), hemorrhagic (n=101; 25%), or both events (n=37; 9%). When these latter values were combined with age (i.e. &gt;60 years) 61% of patients (n=246) would be considered high risk. Therapy for their PV was reported by 96% (n=388) patients, with 89% (361) having been phlebotomized, 72% (n = 291) received aspirin, 64% (n = 261) having received 1 or more myelosuppressive agent (hydroxyurea 53% (n = 216), anagrelide 22% (n = 88), interferon-alpha 16% (n = 63)). Amongst patients whom were phlebotomized over the past year (43%; n =174: median 4 units (range 1–18)), 53% (n = 92) received concurrent myelosuppressive therapy. Amongst patients whom originally, but no longer required phlebotomy 35% (n = 142), 94% (n = 134) were receiving myelosuppressive treatments. QOL assessments indicated fatigue as measured by both instruments is clearly increased across the PV respondents compared to published controls for those instruments (p&lt;0.001). Additionally, although the burden of fatigue was not significantly higher in “high-risk” PV, fatigue levels were higher amongst those with prior thrombo-hemorrhagic events (p=0.03, or both types of events p&lt;0.01). In regards to the impact of PV therapy upon fatigue, the burden of this symptom was not significantly diminished for those individuals on phlebotomy alone compared to those on cytoreductive therapy. Neither did fatigue levels correlate with the frequency or intensity of phlebotomy. Additionally, although fatigue burden was high (compared to controls) amongst patients on cytoreductive therapy, no agent had a clear advantage in alleviating (or disadvantage in exacerbating) fatigue. Conclusions: Fatigue amongst patients with PV is significantly increased compared to controls, and no therapeutic option seems to have a significant advantage with regards to fatigue. Given the multifactorial and subjective nature of fatigue it is impossible to separate the individual contributions of disease activity and therapy to the burden of fatigue in these patients. Hopefully, targeted therapy against the molecular origins of myeloproliferation in these patients will lead to better improvements in fatigue than current options offer.

Abstract Background: Chronic lymphocytic leukemia (CLL) can have a profound effect on the quality of life (QOL) of patients living with the illness. To our knowledge, no studies to date have evaluated the influence of the doctor-patient relationship on patient’s emotional distress or QOL. Methods: We conducted an international, web-based survey of patients with CLL using standardized instruments to evaluate QOL. Additional questions on the survey explored how often patients thought about their disease and evaluated their satisfaction with specific aspects of their relationship with the physician caring for them. Patients were also asked to indicate what phrases their physicians had used to describe/characterize CLL. Results: Between June and October 2006, 1482 patients responded to the survey. The diagnosis of CLL was validated in a randomly selected subset of patients. Over half (55.9%; n=822) of patients reported they thought about their CLL diagnosis daily. Although the proportion of patients who thought about CLL daily decreased with time, two or more years after diagnosis over 50% of patients still thought about their disease every day. When asked to indicate their satisfaction with various aspects of the physician caring for their CLL, more than 90% (n=1340) of patients felt their doctor had a good understanding of how their disease was progressing (i.e., the stage, blood counts, lymph nodes) but only 69% (n=1024) felt their physician had a good understanding of how CLL affected their QOL (anxiety, worry, fatigue, etc.). Similarly, while 90% (n=1324) of patients felt comfortable talking to their doctor about treatment and management of CLL, only 77% (n=1134) felt comfortable talking to their doctor about how CLL affected QOL. Reported satisfaction with their physician in these areas strongly related to patients’ measured emotional and overall QOL on standardized instruments (all p&lt;0.001). This effect on QOL remained (p&lt;0.002) after adjustment for age, extent of co-morbid health conditions, measured fatigue, and treatment status in a regression analysis. Finally, patients were asked to indicate whether the physician caring for them had used specific phrases to describe CLL. Thirty-three percent of patients had been told “CLL is the ‘good’ leukemia,” 24% had been told “don’t worry about your CLL,” and 35% had been told “if you could pick what cancer to have, this is what you would choose.” Overall, 52% of patients had received one or more of these characterizations of CLL by their physician. The emotional and overall QOL were worse among patients who reported their physician had used these phrases to describe CLL (all p≤0.001). This effect on QOL remained after regression analysis (p&lt;0.002). Patients whose physician had used one of these phrases to describe CLL were also less likely to feel their physician understood how CLL was effecting their QOL and to feel comfortable discussing the effects of CLL on their QOL with their physician (all p&lt;0.001). Conclusions: Physicians play an important role helping patients adjust to the physical, intellectual, and emotional challenges of CLL. The effectiveness with which physicians accomplish these tasks appears to impact the QOL of patients with CLL. Additional studies exploring how physicians can best support patients with CLL are needed.

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.