Table 2:

Selected Biomarker Studies that have used Patient-Reported Outcomes as the Peripheral Neuropathy Endpoint

PRO Instrument	PRO Scale	Outcome used in analysis	Parallel analysis of CTCAE	Biomarker	n	Findings	Ref
FACT-NTx	NTx score	Case defined as ≥ 20% worsening of cumulative score from baseline	No	Proteomics	17	Hypothesis-generating association with a protein signature	11
EORTC QLQ-CIPN20	CIPN8*	Cumulative score at each week of treatment	No, but used PN-induced treatment disruption	Paclitaxel PK and clinical variables	60	PRO associated with cumulative dose, age, and alcohol intake. Treatment disruption associated with cumulative dose and paclitaxel pharmacokinetics	12
	CIPN8*	Ordinal groups empirically derived from cumulative score	No	GWAS and clinical variables	680	PRO associated with age, smoking, and drinking. Hypothesis-generating associations with genetics	13
	CIPN20	Cases and controls defined by selecting phenotypic extremes from distribution of increase in cumulative score throughout treatment	No	Candidate gene sequencing	119	PRO-derived cases carried more deleterious variants in genes associated with hereditary neuropathy	9
EORTC QLQ-OV28	Two neuropathy questions	Cases defined as response of “Quite a Bit” or “Very Much” on either question	Yes	Candidate genotypes and clinical variables	454	PRO associated with age, residual disease. CTCAE associated with age, bevacizumab, and bowel resection. Hypothesis-generating associations with genetics	10

^*:CIPN9 Sensory subscale without question 18 (difficulty hearing)

Abbreviations: PK: pharmacokinetics, GWAS: Genome-wide association study