Table 4.

Longitudinal analysis of moderate or marked clinician-assessed late normal tissue effects for patients with at least one annual clinical assessment (n=3975)

		Number of moderate or marked events/total number of assessments over follow-up	Odds ratio for schedule (95% CI)	p value for comparison with 40 Gy	p value for comparison between 27 Gy and 26 Gy	Odds ratio for years of follow-up (95% CI); p value
Any adverse event in the breast or chest wall*		..	..	..	..	0·98 (0·96–1·00); 0·055
	40 Gy	651/6121 (10·6%)	1 (ref)	..	..	..
	27 Gy	1004/6303 (15·9%)	1·55 (1·32–1·83)	<0·0001	..	..
	26 Gy	774/6327 (12·2%)	1·12 (0·94–1·34)	0·20	0·0001	..
Breast distortion†		..	..	..	..	0·99 (0·95–1·02); 0·38
	40 Gy	232/5724 (4·0%)	1 (ref)	..	..	..
	27 Gy	363/5953 (6·1%)	1·51 (1·15–1·97)	0·0028	..	..
	26 Gy	299/5945 (5·0%)	1·20 (0·91–1·60)	0·19	0·083	..
Breast shrinkage†		..	..	..	..	1·03 (1·00–1·06); 0·023
	40 Gy	330/5728 (5·8%)	1 (ref)	..	..	..
	27 Gy	503/5944 (8·5%)	1·50 (1·20–1·88)	0·0004	..	..
	26 Gy	369/5943 (6·2%)	1·05 (0·82–1·33)	0·71	0·0018	..
Breast induration (tumour bed)†		..	..	..	..	1·00 (0·96–1·04); 0·95
	40 Gy	185/5713 (3·2%)	1 (ref)	..	..	..
	27 Gy	304/5948 (5·1%)	1·56 (1·19–2·05)	0·0013	..	..
	26 Gy	236/5937 (4·0%)	1·19 (0·90–1·59)	0·23	0·047	..
Breast induration (outside tumour bed)†		..	..	..	..	0·96 (0·90–1·02); 0·17
	40 Gy	45/5712 (0·8%)	1 (ref)	..	..	..
	27 Gy	137/5943 (2·3%)	2·79 (1·74–4·50)	<0·0001	..	..
	26 Gy	97/5930 (1·6%)	1·90 (1·15–3·14)	0·013	0·059	..
Telangiectasia		..	..	..	..	1·21 (1·14–1·29); <0·0001
	40 Gy	63/6087 (1·0%)	1 (ref)	..	..	..
	27 Gy	100/6272 (1·6%)	1·68 (1·07–2·65)	0·025	..	..
	26 Gy	102/6300 (1·6%)	1·53 (0·96–2·43)	0·070	0·65
Breast or chest wall oedema		..	..	..	..	0·73 (0·69–0·78); <0·0001
	40 Gy	89/6097 (1·5%)	1 (ref)	..	..	..
	27 Gy	217/6287 (3·4%)	2·18 (1·57–3·03)	<0·0001	..	..
	26 Gy	155/6318 (2·4%)	1·47 (1·03–2·09)	0·032	0·0097	..
Breast or chest wall discomfort		..	..	..	..	0·93 (0·89–0·97); 0·0003
	40 Gy	234/6086 (3·8%)	1 (ref)	..	..	..
	27 Gy	269/6285 (4·3%)	1·10 (0·86–1·40)	0·44	..	..
	26 Gy	250/6309 (4·0%)	0·98 (0·76–1·26)	0·86	0·35	..

Results for years of follow-up show trend in normal tissue effects over follow-up across all fractionation schedules. p values are calculated by Wald test; odds ratios are estimated from the generalised estimating equations model including all follow-up data and show relative odds of moderate or marked adverse event (vs none or mild) for each pairwise comparison of fractionation schedules across all follow-up assessments.

^*Includes shrinkage, induration, telangiectasia, or oedema.

^†Patients who had breast conservation surgery or mastectomy with reconstruction.