Comparison of Provider-Assessed and Patient-Reported Outcome Measures of Acute Skin Toxicity During a Phase III Trial of Mometasone Cream Versus Placebo During Breast Radiotherapy: The North Central Cancer Treatment Group (N06C4)

Abstract

Purpose Considerable interobserver variability exists among providers and between providers and patients when measuring subjective symptoms. In the recently published Phase III N06C4 trial of mometasone cream vs. placebo to prevent radiation dermatitis, the primary provider–assessed (PA) endpoint, using the Common Toxicity Criteria for Adverse Events (CTCAE), was negative. However, prospectively planned secondary analyses of patient-reported outcomes (PROs), using the Skindex-16 and Skin Toxicity Assessment Tool (STAT), were positive. This study assesses the relationship between PA outcomes and PROs. Methods and Materials Pearson correlation coefficients were calculated to compare the three tools. Statistical correlations were defined as follows: <0.5, mild; 0.5–0.7, moderate; and >0.7, strong. Results CTCAE dermatitis moderately correlated with STATerythema, and CTCAE pruritus strongly correlated with STAT itching. CTCAE pruritus had a moderate correlation with Skindex-16 itching. Comparing the 2 PRO tools, Skindex-16 itching correlated moderately with STAT itching. Skindex-16 burning, hurting, irritation, and persistence all showed the strongest correlation with STAT burning; they showed moderate correlations with STAT itching and tenderness. Conclusions The PRO Skindex-16 correlated well with the PRO portions of STAT, but neither tool correlated well with CTCAE. PROs delineated a wider spectrum of toxicity than PA measures and provided more information on rash, redness, pruritus, and annoyance measures compared with CTCAE findings of rash and pruritus. PROs may provide a more complete measure of patient experience than single-symptom, PA endpoints in clinical trials assessing radiation skin toxicity.

The association between clinician-based common terminology criteria for adverse events (CTCAE) and patient-reported outcomes (PRO): a systematic review

“…This included disease specific modules of the European Organization for Research and Treatment of Cancer (EORTC) [12–20] and Functional Assessment of Cancer Therapy (FACT) [21–23] instruments, as well as the dermatology-specific Skindex-16, [24, 25] the EuroQol EQ-5D, [26] the Short-Form 36 Health Survey (SF-36) [27], and two recently developed bowel symptom inventories [28, 29]. Patient-adapted versions of the CTCAE were used in four studies [27, 30–32], with visual analog scales used to capture patient-rated AEs in three studies [11, 33, 34].…”

Ionizing Radiation: The Good, the Bad, and the Ugly

“…Over the past few years, patient-reported outcomes have become common instruments to aid in accurate assessment of various symptoms (Neben-Wittich et al ., 2010). Recently, Neben-Wittich et al reported that the Skindex-16 and Skin Toxicity Assessment Tool, two patient-report outcomes (PRO) instruments, did not correlate with CTCAE scoring system.…”

“…The study showed that African-Americans reported more severe post-treatment skin reactions compared to Caucasians after receiving radiation therapy. Both of these studies (Neben-Wittich et al ., 2010; Ryan et al ., 2007) demonstrate that patient-reported information is critical for effective symptom management. Overall, further research is required for development of a standard and accurate scoring system for radiation skin injury.…”

Characterization of skin reactions and pain reported by patients receiving radiation therapy for cancer at different sites

“…Unfortunately, the measures used in this trial (Skindex, SF-36) did not evaluate pain [20]. Neben-Wittich et al compared the Skindex-16, STAT, and NIH CTC-AE in a phase III clinical trial testing mometasone cream versus placebo for radiation dermatitis in breast cancer patients [21]. The patient-reported Skindex-16 and STAT did not correlate with the physician-reported NIH CTC-AE scores.…”