Registry study to assess hair loss prevention with the Penguin Cold Cap in breast cancer patients receiving chemotherapy.

PURPOSE: Chemotherapy-induced alopecia is a distressing side effect of cancer treatment. The aim of this registry study was to assess efficacy and tolerability of scalp hypothermia using Penguin Cold Caps (Penguin) in breast cancer patients. METHODS: Hair loss was assessed by patients using a 100-point Visual Analog Scale (VAS) and by physicians using the 5-point Dean Scale at baseline, every 3-4 weeks during chemotherapy, and at least 1 month after completion of chemotherapy. The primary efficacy endpoint for success was defined as ≤50% hair loss by patient report (VAS) at follow-up (FUP). Tolerability and satisfaction were assessed by patient report. RESULTS: 103 patients enrolled between 7/2010 and 6/2015; 97 are evaluable for the primary endpoint. Chemotherapy included docetaxel/cyclophosphamide (TC; n = 50) for 4-6 cycles every 3 weeks, weekly paclitaxel for 12 weeks then doxorubicin/cyclophosphamide (P/AC; n = 23) for 4 cycles every 2-3 weeks, AC then paclitaxel (AC/P; n = 10), docetaxel/carboplatin ± trastuzumab (TCH; n = 4) for 4-6 cycles every 3 weeks. Overall, 61% of patients successfully prevented CIA; impact was regimen specific: TCH 100%, TC × 4 84%, TC × 5-6 50%, P/AC 43%, AC/P 20%. The most common toxicity was headache, reported by 78.5% of patients with mean pain level 37/100. Satisfaction among those who completed scalp cooling (SC) and FUP ranged from 74 to 100%. All patients who completed SC/FUP recommended Penguin. CONCLUSIONS: Scalp hypothermia with Penguin is effective in reducing alopecia, particularly for non-anthracycline-based shorter regimens. Penguin was well tolerated and viewed favorably by most patients.

Tracking cognitive change over 24 weeks with longitudinal functional magnetic resonance imaging in Alzheimer's disease.

BACKGROUND: Previous studies have revealed that functional magnetic resonance imaging (fMRI) blood oxygen level-dependent (BOLD) signal in specific brain regions correlates with cross-sectional performance on standardized clinical trial measures in Alzheimer's disease (AD); however, the relationship between longitudinal change in fMRI-BOLD signal and neuropsychological performance remains unknown. OBJECTIVE: To identify changes in regional fMRI-BOLD activity that tracks change in neuropsychological performance in mild AD dementia over 6 months. METHODS: Twenty-four subjects (mean age 71.6) with mild AD dementia (mean Mini Mental State Examination 21.7, Global Clinical Dementia Rating 1.0) on stable donepezil dosing participated in two task-related fMRI sessions consisting of a face-name paired associative encoding memory paradigm 24 weeks apart during a randomized placebo-controlled pharmaco-fMRI drug study. Regression analysis was used to identify regions where the change in fMRI activity for Novel > Repeated stimulus contrast was associated with the change scores on postscan memory tests and the Free and Cued Selective Reminding Test (FCSRT). RESULTS: Correlations between changes in postscan memory accuracy and changes in fMRI activity were observed in regions including the angular gyrus, parahippocampal gyrus, inferior frontal gyrus and cerebellum. Correlations between changes in FCSRT-free recall and changes in fMRI were observed in regions including the inferior parietal lobule, precuneus, hippocampus and parahippocampal gyrus. CONCLUSION: Changes in encoding-related fMRI activity in regions implicated in mnemonic networks correlated with changes in psychometric measures of episodic memory retrieval performed outside the scanner. These exploratory results support the potential of fMRI activity to track cognitive change and detect signals of short-term pharmacologic effect in early-phase AD studies.

Test-retest reliability of memory task functional magnetic resonance imaging in Alzheimer disease clinical trials.

OBJECTIVE: To examine the feasibility and test-retest reliability of encoding-task functional magnetic resonance imaging (fMRI) in mild Alzheimer disease (AD). DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Memory clinical trials unit. PARTICIPANTS: We studied 12 patients with mild AD (mean [SEM] Mini-Mental State Examination score, 24.0 [0.7]; mean Clinical Dementia Rating score, 1.0) who had been taking donepezil hydrochloride for more than 6 months from the placebo arm of a larger 24-week study (n = 24, 4 scans on weeks 0, 6, 12, and 24, respectively). INTERVENTIONS: Placebo and 3 face-name, paired-associate encoding, block-design blood oxygenation level-dependent fMRI scans in 12 weeks. MAIN OUTCOME MEASURES: We performed whole-brain t maps (P < .001, 5 contiguous voxels) and hippocampal regions-of-interest analyses of extent (percentage of active voxels) and magnitude (percentage of signal change) for novel-greater-than-repeated face-name contrasts. We also calculated intraclass correlation coefficients and power estimates for hippocampal regions of interest. RESULTS: Task tolerability and data yield were high (95 of 96 scans yielded favorable-quality data). Whole-brain maps were stable. Right and left hippocampal regions-of-interest intraclass correlation coefficients were 0.59 to 0.87 and 0.67 to 0.74, respectively. To detect 25.0% to 50.0% changes in week-0 to week-12 hippocampal activity using left-right extent or right magnitude with 80.0% power (2-sided α = .05) requires 14 to 51 patients. Using left magnitude requires 125 patients because of relatively small signal to variance ratios. CONCLUSIONS: Encoding-task fMRI was successfully implemented in a single-site, 24-week, AD randomized controlled trial. Week 0 to 12 whole-brain t maps were stable, and test-retest reliability of hippocampal fMRI measures ranged from moderate to substantial. Right hippocampal magnitude may be the most promising of these candidate measures in a leveraged context. These initial estimates of test-retest reliability and power justify evaluation of encoding-task fMRI as a potential biomarker for signal of effect in exploratory and proof-of-concept trials in mild AD. Validation of these results with larger sample sizes and assessment in multisite studies is warranted.