1. Comparing and Validating Simple Measure of Patient-reported Peripheral Neuropathy for NCCTG Clinical Trials: a Pooled Analysis of 2440 Patients Heshan Liu 1, Angelina D. Tan 1, Axel Grothey 1, Paul L. Schaefer 2, Jan C. Buckner 1, Charles L. Loprinzi 1, Roscoe F. Morton 3, Jeff A. Sloan 1 1 Mayo Clinic, Rochester, MN; 2 Toledo Community Hospital Oncology Program, Toledo, OH; 3 Medical Oncology & Hematology Associates – Pleasant, Des Moines, IA; Abstract Background: The introduction of new anti-cancer therapies which cause patients(pts) to incur peripheral(PN) has required the development of new methods to assess this treatment outcome. This study compared and validated alternative methods of assessing Patient-reported PN in a series of North Central Cancer Treatment Group (NCCTG) clinical trials. Methods: Data were combined from 5 NCCTG trials (2440 pts) that used single-item questions scaled 0-100 relating to numbness and tingling respectively in fingers and toes to measure PN. Patient quality of life (QOL) was assessed using UNISCALE, Symptom Distress Scale (SDS), Profile of Mood States (POMS), Brief Pain Inventory (BPI) and Subject Global Impression of Change (SGIC). Associations between items were tested using Bland-Altman method and correlation. Wilcoxon tests compared QOL scores between pts with PN (score >40) vs. no PN. Change in PN and QOL was compared with a 20-point change defined as clinically meaningful. Minimal important differences (MID) were estimated using both anchor-based approach and distribution-based methods. Results: At baseline, the proportion of patient-reported PN was 11% (numbness) and 10% (tingling); and 18% on each at last assessment. The correlation between PN items at baseline and last assessment was 0.8, with an average difference of <1 point on the 100-point scale. The MID estimate of SGIC in overall QOL, Physical Condition and Emotional State were 24, 21, 25 for numbness (respectively); and 19, 18, 17 for tingling (respectively). The distribution-based MID estimate was 12 for both PN items. Pts with substantial PN reported an average of 10 points lower QOL, mood and worse SDS and a 20 point- deficit in the BPI interference items. Pts with ≤20 points worsening in PN reported significant declines in SDS (p<0.001), worst pain (p<0.02), but not in POMS (p=0.64) or overall QOL (p=0.86). Conclusions: The two PN items for numbness and tingling were redundant. Anchor-based MID methods produced larger and inconsistent estimates relative to the distribution-based methods. Evidence of criterion validity and responsiveness indicates that these simple measures of PN can be used successfully in cancer clinical trials. Background Peripheral neuropathy(PN) is a common and intrusive side effect of chemotherapy. The assessment of PN is typically done via the common toxicity criteria (CTC), although patient reported outcome- based assessments have potentially greater sensitivity. The purpose of this investigation was to asses the relative sensitivity of the CTC and simple single-item numerical analogue scale assessments in detecting the onset and severity of PN in patients receiving oxaliplatin. QOL Scores by Peripheral Neuropathy QOL ItemsNumbnessTingling Uniscale Overall QOL0.230.21 SDS Total0.25 POMS Total0.160.23 BPI Worst Pain0.320.30 BPI Average Pain0.270.26 BPI Work Interference0.410.38 BPI Pain Interference0.430.39 Conclusions Simple single-item measures of PN are psychometrically sound Either of the two items for assessing PN (numbness or tingling) can be used (redundant) Minimum Important Difference ProtocolStudy DescriptionAccrualQOL Tools N00C3Neuropathy/Gabapentin115 Uniscale, SDS, SGIC, POMS, BPI N01C3 Peripheral Neuropathy/ Lamotrigine 131 Uniscale, SDS, SGIC, POMS, BPI N05C3 Peripheral Neuropathy/Vitamin E 207-- N9741 Advanced Colon CPT11/5FU/OXAL 1751UNISCALE, SDS N9841 Advanced Colorectal CPT-11/OXAL/5-FU/CF 507UNISCALE, SDS Trials Included in the Analyses CharacteristicsTotal (N=2440) Age (Median, Range)61 (19.0 – 88.0) %Male55 Race White2137 (87.6%) Black/African American167 (6.8%) Native Hawaiian /Other Pacific Islander 6 (0.2%) Asian28 (1.1%) American Indian/Alaskan Native 13 (0.5%) Not reported89 (3.6%) % PRPN: Numbness215 (10.7%) % PRPN: Tingling201 (10%) Disease Status N/A423 Measurable1668 (82.7%) Evaluable349 (17.3%) ECOG PS N/A423 0-11930 (95.7%) 287 (4.3%) Bland Altman Plot at Baseline Overall Patient CharacteristicsCorrelation between PN and QOL Items at Baseline QOL Items ≥20 worsening (N=617) No 20 worsening (N=963) Kruskal-Wallis P-value Uniscale Overall QOL-4.8-4.90.8624 SDS Total-1.51.000002 POMS Total-0.81.40.6397 BPI Worst Pain-7.39.40.0193 BPI Average Pain-2.97.60.0869 BPI Work Interference-0.414.80.0248 BPI Pain Interference-1.210.20.1018 Comparison of change from Baseline QOL Scores by Decreasing PN Score PN assessments are measuring something unique The two PN assessments are psychometrically comparable PN impacts overall QOL, symptom distress and pain Individual changes in PN correspond to changes in mood and pain 10-point MID is supported. Anchor-based MID’s larger All P values<.025 r between PN numbness and tingling : 0.81 r between average and difference : 0.08 Contact Information Heshan Liu, M.S. liu.heshan@mayo.edu Jeff Sloan, Ph.D. jsloan@mayo.edu |---------------------- Anchor Based ----------------------| Distribution Based --- ---|