GOECP/SEOR radiotheraphy guidelines for non-small-cell lung cancer

Table 3 Accelerated fractionation-hyperfractionation studies

Ref.	Study type	Number of patients	Radiotherapy	Chemotherapy	Results	Toxicity
[65,66]	Phase III RCT	n = 563: Stage I (29%), II (7%), IIIA (38%), IIIB (23%). Similar in both arms	[cRT: 60 Gy, 2 Gy/d (6 wk). INP 44 Gy + boost 16 Gy tumour and involved nodes] vs (CHART: 54 Gy, 1.5 Gy/3 times/d, 6 h apart, on 12 consecutive days). INP 37.5 Gy in 25 fx + boost 16.5 Gy in 11 Gy to tumour and involved nodes	No	Absolute 2-yr survival improvement of 9%: 20% cRT vs 29% CHART. 21% relative risk reduction for PL. Major improvement in squamous cell disease: 13% 2-yr survival: 20% cRT vs 33% CHART. 25% relative risk reduction of PL	Clinical pneumonitis 19% cRT and 10% CHART
[67]	Phase III RCT	n = 141: Stage III A-B unresectable. ECOG 0-1	[cRT: 64 Gy, 2 Gy/d (6 ½ wk)] vs [HART: 57.6 Gy, 1.5 Gy 2 times/d (2.5 wk)]	Induction: Carboplatin AUC 6 + paclitaxel 225 mg/m2 2 cycles prior to RT	2-yr OS: 44% HART vs 24% cRT; 3 yr: 34% vs 14%. Non-significant trend towards better survival with HART. Feasible treatment. Trial close early due to slow recruitment	Esophagitis ≥ G3: 23% HART vs 15% cRT. Pneumonitis ≥ G3: 0 HART vs 10% cRT
[68]	Phase III RCT	n = 406: Stage I 10%, II 5%, IIIA 38%, IIIB 46%. Similar in both arms	(CHARTWEL: 60 Gy, 1.5 Gy 2 times/d in 2.5 wk) vs (cRT: 66 Gy, 2 Gy/d, 6.5 wk)	Neoadjuvant 27%. Similar in both arms	Better LC in CHARTWEL. No difference between arms in OS at 2, 3, 5 yr. Better LC CHARTWEL trend in advanced stages and after neoadjuvant ChT	Greater acute dysphagia CHARTWEL. Greater radiological pneumonitis CHARTWEL, no differences in clinical pneumonitis
[69]	Retrospective	n = 849, 9 United Kingdom centres. Stage I 33%, II 13%, IIIA 24%, IIIB 24%, IV 1%	CHART: 54 Gy, 1.5 Gy/3 times/d, 6 h apart, in 12 d	Induction: 27% patients, 82% stage III (96% platinum doublets: Cisplatin or carboplatin with vinorelbine, gemcitabine or paclitaxel)	OS 2 and 3 yr: 47% and 32%. OS 3 yr: 38% stage I and 27% stage III. Tendency to better survival in stage III after ChT	Esophagitis, pneumonitis ≥ G3 5%

RCT: Randomised controlled trial; cRT: Conventional radiotherapy; ENI: Elective nodal irradiation; CHART: Continuous Hyperfractionated Accelerated Radiotherapy Trial; OS: Overall survival; RT: Radiotherapy; LC: Local control; CHARTWEL: Continuous Hyperfractionated Accelerated Radiotherapy Weekend Less.