Of 35 participants who consented, 34 completed the baseline assessment and 32 completed at least two assessments while on chemotherapy. Most participants were female, who received adjuvant taxane chemotherapy for breast cancer. The demographic details of participants are summarised in Table 1.
Treatment intensity was > 75% of planned in 32/34 participants. Dose modification or early cessation of chemotherapy occurred in 26/34 (76%) patients. CIPN was the most common reason reported, affecting 50% of patients regardless of cancer diagnosis. Two participants only achieved 50% of planned treatment; one due to fever and infection, and one chose to stop chemotherapy due to the COVID-19 pandemic.
Participants completed a median of 4 assessments (range 2–5), dependent on their chemotherapy cycle length and duration of adjuvant therapy. Figure 1 outlines the flow of participants through the study.
The primary endpoint was evaluable for 28 participants. Reasons for missing data in 5 patients are: 1) 3 participants declined the VR assessment due to fatigue; 2) no assessor was available for 1 assessment; and, 3) one patient relocated treatment to a different hospital.
The reduced number of assessments at the 3- (n = 22) and 6- (n = 23) month post chemotherapy timepoints were predominantly due to reduced face-to-face visits in the context of the COVID-19 pandemic.
Primary endpoint: VR balance threshold
A reduction in balance threshold was observed in 10/28 (36%) of participants assessed at the end of chemotherapy, indicating that they could not maintain their balance at the same level of challenge as prior to chemotherapy. Most patients reduced their balance threshold by one level, but one participant patient dropped by 12 levels. Four participants (15%) had a balance threshold reduce by greater than two levels.
Table 2 summarises the neurotoxicity parameters assessed in the cohort. Violin plots (Fig. 2) summarise the distribution of scores for each outcome measured, with point estimates and 95% confidence interval (CI) reported in Supplementary material S2. Most participants (n = 24, 85%) developed CIPN during their chemotherapy treatment as assessed via CTCAE, with any-grade peripheral neuropathy symptoms persisting 6 months post-chemotherapy in 72% of patients (n = 16).
For clinician grade of neuropathy (CTCAE), Friedman’s test on multiply imputed data set indicated a significant difference in neuropathy grade between baseline assessment and each of the timepoints (p = < 0.01). Wilcoxon’s test indicated higher grade of neuropathy (median = 2) at post-treatment, 3 months post-treatment and six months post-treatment compared with neuropathy grade at baseline (median = 0).
For the FACT/GOG-Ntx13, results of the pooled set of multiply-imputed data indicated significant differences across the four periods. Compared to the mean score at baseline (M = 3.3, 95% CI: 1.9–4.8), the mean score at the three post-chemotherapy time points was significantly higher, indicating more severe neuropathy symptoms (M = 12.7, 95% CI: 9.8–15.6 at end of the treatment, M = 11.0, 95% CI: 7.5–14.4 at three months post-treatment, M = 11.2, 95% CI: 8.1–14.4 at six months post-treatment).
For clinically scored neuropathy (TNSc), results for the pooled set of multiply imputed data and multiply imputed data set indicated a significant difference in mean TNSc score across four periods. Compared to the mean score at baseline (M = 2.4, 95% CI: 1.5–3.2), mean scores at subsequent time-points were higher, indicating more neuropathy following chemotherapy (M = 4.5, 95% CI: 3.4–5.7 at end of the treatment), which persisted following cessation (M = 4.6, 95% CI: 3.5–5.7 at three months post-treatment, M = 5.2, 95% CI: 3.4–7.0 at six months post-treatment).
Results of the repeated measures ANOVA for complete cases data indicated no significant difference in the ‘Timed Up-and-Go’ across the four assessments (n = 9, Wilk’s lambda = 0.57, F (3, 6) = 1.5, p = .31).
Frequency of falls
There were no participants or researcher injuries relating to the VR assessments. A fall/near fall was reported by 12 of 34 patients during the study period. Seven patients had falls, three had a near fall, and two had both. Three patients reported multiple episodes. Of the 18 falls or near falls reported, 13 occurred while on chemotherapy, two were within three months of completing chemotherapy, and three were between 3 and six months of treatment completion.
Balance threshold measured following the reported fall/near fall was significantly lower compared to times when no fall was reported (mean 10.3 vs 14.2, p value = 0.0002). Similarly, scores for clinical and patient reported neuropathy showed significantly more impairment from CIPN in participants who had experienced falls/near falls, compared to when no fall was reported (Table 3).