Table 3.
Intention-to-treat analysis: CIPN signs and symptoms.
| Group | pre | post0 | post3 | post6 | pre–post0 | Between-group comparison [pre–post0] | ||||
|---|---|---|---|---|---|---|---|---|---|---|
| Outcome | mean ± SD | mean ± SD | mean ± SD | mean ± SD | Adjusteda mean change (95% CI) | Comparison | Adjusteda between-group difference (95% CI) | P value | ES (95% CI) | |
| Total Neuropathy Score | ||||||||||
| TNSr [sum score, 0–36] | SMT | 1.4 ± 2 | 7.2 ± 4.1 | 8.2 ± 4.2 | 7.1 ± 4 | 4.5 (2.8 to 6.2) | SMT vs. UC | 0.3 (−1.6 to 2.3) | 0.908 | −0.15 (−0.57 to 0.27) |
| RT | 1.6 ± 1.5 | 7.6 ± 4.7 | 6.5 ± 4.3 | 6.8 ± 4.1 | 4.7 (3.1 to 6.2) | RT vs. UC | 0.5 (−1.4 to 2.4) | 0.809 | −0.21 (−0.62 to 0.19) | |
| UC | 2.3 ± 3.1 | 7.8 ± 4.7 | 7.6 ± 5.1 | 6.5 ± 4 | 4.2 (2.5 to 5.8) | SMT vs. RT | −0.2 (−2.2 to 1.8) | 0.982 | 0.07 (−0.36 to 0.49) | |
| TNSc [sum score, 0–28] | SMT | 0.5 ± 1.2 | 4.9 ± 3.1 | 5.8 ± 3.5 | 5.3 ± 3.4 | 3.2 (1.8 to 4.5) | SMT vs. UC | −0.1 (−1.7 to 1.5) | 0.983 | 0.08 (−0.33 to 0.48) |
| RT | 0.7 ± 1.1 | 5.6 ± 3.6 | 5.1 ± 3.6 | 5 ± 3.6 | 3.7 (2.5 to 5.0) | RT vs. UC | 0.4 (−1.1 to 2) | 0.773 | −0.28 (−0.68 to 0.12) | |
| UC | 1.4 ± 2.1 | 5.8 ± 3.7 | 5.7 ± 4.4 | 4.9 ± 4 | 3.3 (2.0 to 4.6) | SMT vs. RT | −0.6 (−2.1 to 1) | 0.673 | 0.36 (−0.06 to 0.77) | |
| TNSm [sum score, 0–24] | SMT | 0.4 ± 1 | 4.2 ± 2.8 | 5.2 ± 3.2 | 4.8 ± 3.1 | 2.8 (1.6 to 4.0) | SMT vs. UC | −0.1 (−1.5 to 1.4) | 0.995 | 0.04 (−0.37 to 0.45) |
| RT | 0.7 ± 1.1 | 5.1 ± 3.4 | 4.5 ± 3.2 | 4.4 ± 3.1 | 3.6 (2.4 to 4.7) | RT vs. UC | 0.7 (−0.7 to 2.1) | 0.438 | −0.51 (−0.91 to −0.1) | |
| UC | 1.2 ± 1.9 | 5 ± 3.2 | 4.9 ± 3.8 | 4.3 ± 3.5 | 2.8 (1.6 to 4.0) | SMT vs. RT | −0.8 (−2.2 to 0.6) | 0.395 | 0.55 (0.13 to 0.97) | |
| Nerve conduction studies | ||||||||||
| CMAP (mV) | SMT | 7.6 ± 3 | 5.7 ± 3 | 5.5 ± 2.5 | 6.4 ± 2.6 | −1.4 (−2.2 to −0.7) | SMT vs. UC | 0.1 (−0.9 to 1) | 0.984 | 0.02 (−0.38 to 0.42) |
| RT | 8 ± 2.5 | 6.1 ± 2.7 | 5.7 ± 2.7 | 6.4 ± 2.6 | −1.3 (−1.9 to −0.6) | RT vs. UC | 0.2 (−0.6 to 1.1) | 0.813 | 0.08 (−0.30 to 0.46) | |
| UC | 7.4 ± 2.9 | 5.4 ± 2.4 | 6.2 ± 2.8 | 5.9 ± 2.7 | −1.5 (−2.2 to −0.8) | SMT vs. RT | −0.2 (−1.1 to 0.8) | 0.913 | −0.06 (−0.45 to 0.34) | |
| SNAP (µV) | SMT | 10.8 ± 4.3 | 7.6 ± 3.9 | 7.2 ± 3.6 | 8 ± 3.8 | −3.2 (−4.5 to −1.8) | SMT vs. UC | −0.6 (−2.3 to 1) | 0.612 | −0.14 (−0.55 to 0.26) |
| RT | 10.6 ± 4.3 | 8.1 ± 4.4 | 8.4 ± 4.1 | 8.2 ± 4.5 | −2.5 (−3.6 to −1.3) | RT vs. UC | 0.1 (−1.5 to 1.6) | 0.996 | 0.01 (−0.38 to 0.40) | |
| UC | 11.3 ± 5 | 8.2 ± 5.1 | 8.9 ± 5.1 | 9.2 ± 5.5 | −2.5 (−3.8 to −1.3) | SMT vs. RT | −0.7 (−2.3 to 0.9) | 0.562 | −0.16 (−0.56 to 0.25) | |
| NCV (peroneal) (m/s) | SMT | 48 ± 3.7 | 46.8 ± 3.7 | 46.1 ± 4.3 | 46.3 ± 4.1 | −2.3 (−3.5 to −1.1) | SMT vs. UC | −0.2 (−1.6 to 1.2) | 0.943 | −0.05 (−0.46 to 0.35) |
| RT | 48.8 ± 3.6 | 46.9 ± 4.1 | 48.2 ± 4.2 | 47.9 ± 3.8 | −2.2 (−3.2 to −1.2) | RT vs. UC | −0.1 (−1.4 to 1.2) | 0.988 | −0.02 (−0.41 to 0.36) | |
| UC | 48.7 ± 3.8 | 47.2 ± 4.4 | 47.3 ± 4.4 | 47.3 ± 3.8 | −2.1 (−3.2 to −1.0) | SMT vs. RT | −0.1 (−1.5 to 1.3) | 0.981 | −0.03 (−0.44 to 0.38) | |
| NCV (sural) (m/s) | SMT | 48.4 ± 5 | 46.4 ± 4.8 | 46.8 ± 4.7 | 45.8 ± 5.2 | −3.1 (−5.2 to −0.9) | SMT vs. UC | 0 (−2.7 to 2.6) | 0.999 | −0.01 (−0.42 to 0.40) |
| RT | 48 ± 4.7 | 45.9 ± 5.9 | 45.8 ± 6.1 | 45.6 ± 4.8 | −3.1 (−5.0 to −1.2) | RT vs. UC | −0.1 (−2.6 to 2.4) | 0.997 | −0.01 (−0.41 to 0.38) | |
| UC | 48.4 ± 6.5 | 46.3 ± 5.3 | 45.3 ± 3.6 | 46.1 ± 3.9 | −3.0 (−5.1 to −1.0) | SMT vs. RT | 0.0 (−2.6 to 2.7) | 1.00 | 0.00 (−0.41 to 0.42) | |
| Patient-reported CIPN symptoms [EORTC QLQ-CIPN20] | ||||||||||
| CIPN-15 [sum score, 0–100] | SMT | 1.9 ± 4 | 14.2 ± 14.5 | 15.2 ± 19.1 | 12.1 ± 13.5 | 9.8 (3.7 to 16.0) | SMT vs. UC | 2.2 (−5.2 to 9.5) | 0.761 | −0.47 (−0.87 to −0.07) |
| RT | 2.2 ± 3.5 | 15.4 ± 17.9 | 14.4 ± 16.3 | 12.1 ± 14.3 | 10.4 (5.1 to 15.7) | RT vs. UC | 2.7 (−4.3 to 9.7) | 0.624 | −0.59 (−0.98 to −0.2) | |
| UC | 3.6 ± 5.9 | 14.3 ± 15.3 | 14.8 ± 18.7 | 13.3 ± 17.2 | 7.7 (2.0 to 13.4) | SMT vs. RT | −0.6 (−7.9 to 6.8) | 0.983 | 0.12 (−0.28 to 0.52) | |
| Sensory symptoms feet [sum score, 0–100] | SMT | 2 ± 4.9 | 17.5 ± 18 | 18.8 ± 22.4 | 14.4 ± 18.2 | 9.5 (1.6 to 17.3) | SMT vs. UC | −1.5 (−10.9 to 7.9) | 0.925 | 0.23 (−0.17 to 0.63) |
| RT | 1.4 ± 3.3 | 19.4 ± 21.1 | 18.8 ± 22.2 | 17.1 ± 20.2 | 11.9 (5.0 to 18.7) | RT vs. UC | 0.9 (−8.2 to 10) | 0.971 | −0.14 (−0.52 to 0.24) | |
| UC | 4.2 ± 9.3 | 21.5 ± 21.7 | 21 ± 23.4 | 18.4 ± 23.1 | 11 (3.6 to 18.3) | SMT vs. RT | −2.4 (−11.8 to 7) | 0.819 | 0.37 (−0.03 to 0.77) | |
| Motor symptoms feet [sum score, 0–100] | SMT | 2.9 ± 6.3 | 10.4 ± 13.7 | 14.7 ± 21.6 | 8.5 ± 12.7 | 4.8 (−1.0 to 10.7) | SMT vs. UC | 1.4 (−5.6 to 8.4) | 0.885 | −0.17 (−0.56 to 0.23) |
| RT | 2.8 ± 4.9 | 12.3 ± 15.8 | 12.9 ± 17.7 | 11.5 ± 15.4 | 6.6 (1.6 to 11.7) | RT vs. UC | 3.2 (−3.5 to 9.9) | 0.499 | −0.38 (−0.76 to 0.01) | |
| UC | 6.1 ± 11.9 | 12.3 ± 18.2 | 14.2 ± 24 | 13.4 ± 23 | 3.5 (−2.0 to 8.9) | SMT vs. RT | −1.8 (−8.8 to 5.2) | 0.815 | 0.21 (−0.18 to 0.61) | |
| Symptoms hands [sum score, 0–100] | SMT | 2 ± 5.1 | 15.4 ± 16.2 | 15 ± 19.8 | 13 ± 14.4 | 12.5 (5.7 to 19.2) | SMT vs. UC | 4.6 (−3.5 to 12.6) | 0.373 | −0.69 (−1.1 to −0.28) |
| RT | 3.2 ± 6.3 | 15.6 ± 19.9 | 14.2 ± 16.4 | 11.1 ± 16 | 11.1 (5.3 to 17.0) | RT vs. UC | 3.2 (−4.4 to 10.9) | 0.582 | −0.49 (−0.87 to −0.1) | |
| UC | 3.5 ± 8 | 12.8 ± 15.3 | 13.1 ± 19.6 | 11.7 ± 14.6 | 7.9 (1.6 to 14.2) | SMT vs. RT | 1.3 (−6.7 to 9.4) | 0.918 | −0.20 (−0.6 to 0.19) | |
CIPN-15 sum score based on 15 items of the EORTC QLQ-CIPN20 questionnaire, CMAP compound muscle action potential of the peroneal nerve, NCV nerve conduction velocity, pre assessment point before neurotoxic chemotherapy, post0 assessment point 3 weeks after neurotoxic chemotherapy, post3 assessment point 3 months after post0, post6 assessment point 6 months after post0, SD standard deviation, SNAP sensory nerve action potential of sural nerve, TNSc Total Neuropathy Score (clinical), TNSm Total Neuropathy Score (modified), TNSr Total Neuropathy Score (reduced).
The table shows descriptive statistics of clinically, electrophysiologically assessed and subjectively perceived CIPN signs and symptoms for all assessment points. Adjusted mean change (within groups) and between-group differences are only presented for intervention time as revealed by intention-to-treat analyses. Bold value indicates statistical significance at the level of 5%.
aRegression models were adjusted for baseline value, sex, age, and therapy-randomisation strata.