Guidelines
Copyright ©The Author(s) 2022.
World J Clin Oncol. Apr 24, 2022; 13(4): 237-266
Published online Apr 24, 2022. doi: 10.5306/wjco.v13.i4.237
Table 4 Studies of moderate hypofractionated radiotherapy
Ref.
Type of study
Number of patients
Radiotherapy
Chemotherapy
Results
Toxicity
[76]Prospective30, stage III-IVA. ECOG ≥ 260 Gy (20 fx 3 Gy); (BED10 79.4 Gy)Sequential (80% patients)LR 37%. OS 2-yr 38.1%. LR 37%. Distant relapse 57%Acute esophagitis G3 7%. Acute pneumonitis G3 3%. No chronic toxicity
[77]Prospective83 (32 stage III)66 Gy (24 fx 2.75 Gy); (BED10 84 Gy)Sequential 90.6% stage III (platinum + vinorelbine)OS 2 yr 37.5%. SCE 2 yr 41.5%No toxicity ≥ G3
[78]Retrospective300, stage III, inoperable, MEG3 arms: 45 Gy (15 fx 3 Gy); 60-63 Gy (6 wk); > 63 Gy (6 wk)No significant differences in LC, distant control, or OS. > DFS in 60-63 GyLower in hypofractionated arm
[79]Retrospective 609 (9 centres). Stage IA (18%), IB (30.7%), II (14.8%), IIIA (16.4%), IIIB (19.2%). Unresectable or inoperable55 Gy (20 fx 2.75 Gy)ChT 28% (83% stage III). Platinum doublets. Most neoadjuvantOS at 2, 3 and 5 yr: 50%, 36% and 20%. 2 yr OS: stage IA, 72%, stage Ib 51%, stage IIIA 40%. Adenocarcinoma better median survival (31 m) vs squamous (20.4 m). No difference in OS between ChT vs no ChT. Stage III, trend towards better OS with ChTNo toxicity ≥ G3. Pneumonitis G1-2, 15%
[80,82]Retrospective31, stage I (15), II (15), IIIA (57), IIIB (43). Medically inoperable or unresectable3 arms: 66 Gy (24 fx 2.75 Gy) + daily cisplatin (6 mg/m2); same sequential RT after 2 cycles cisplatin/gemcitabine; RT alone 66 Gy (24 fx 2.75 Gy) or 60 Gy (20 fx 3 Gy)Concurrent: Cisplatin daily (6 mg/m2). Sequential: (2 cycles cisplatin/gemcitabine) prior to RTLR 36%, DM 46%. Better RT + ChT than RT alone. 5 yr OS: Concurrent CRT, 23%. No significant difference between concurrent and sequential CRT. LR 36%, DM 46%Severe late toxicity greater in CRT (27% concurrent, 23% sequential) than in RT alone (8%)
[81]Phase III RCT160, stage II/III (11.6%/88.3%). ECOG ≥ 2. Not candidates for ChT/RTcRT 60-66 Gy/30-33 fx vs accelerated hypofx 60 Gy/15 fx 4 GyNon-concurrent ChT. Possible neoadjuvant or adjuvantOS and PFS without significant differences between cRT and hypofxNo G4 toxicity. G3 toxicity: 35% cRT and 18.75% hypofx
[82]Phase III RCT158, stage I (3% sequential, 1% concurrent), II (4% sequential, 5% concurrent), IIIA (45% sequential, 30% concurrent), IIIB (47% sequential, 64% concurrent). Inoperable ECOG 0-166 Gy (24 fx 2.75 Gy)Concurrent: Daily cisplatin (6 mg/m2) + RT 66 Gy (24 fx 2.75 Gy) vs sequential: 2 cycles gemcitabine 1250 mg/m2 days 1, 8 and cisplatin (75 mg/m2 day 2, prior to RT 66 Gy (24 fx 2.75 Gy)No significant differences between the 2 groups in DM, OS, PFS. OS 2 and 3 yr: 39%-34% concurrent and 34%-22% sequential. Both schemes well tolerated. Due to early closure, no conclusions drawnAcute esophagitis G3/4 more common in concurrent (14% vs 5%). Late esophagitis G3 = 4% in both arms. Pneumonitis G3/4 = 18% concurrent and 14% sequential
[83]Phase II RCT130, stage III inoperable. ECOG 0-155 Gy (20 fx 2.75 Gy)Concurrent: Cisplatin 20 mg/m2 days 1-4 and 16-19 and vinorelbine 15 mg/m2 days 1, 6, 15 and 20 RT and 1 or 2 post ChT cycles (CDDP) 80 mg/m2 day 1 and vinorelbine 25 mg/m2 days 1 and 8). Sequential: Cisplatin 80 mg/m2 day 1 and vinorelbine 25 mg/m2 days 1 and 8, x 3-4 cycles before RTNo significant differences. OS 1 yr: 70% concurrent vs 83% sequential and 2 yr: 50% concurrent vs 46% sequential. PFS 1 yr: 74% concurrent vs 85% sequential; 2 yr: 47% concurrent vs 45% sequential. Both safe and effective treatments. Non-significant trend towards better survival with concurrent RT/ChTSimilar esophagitis ≥ G3 in both arms (8.8% concurrent and 8.5% sequential. Pneumonitis ≥ G3: 3.1% concurrent vs 5.2% sequential. No grade 4/5 esophagitis. G3 neutropenia lower in concurrent (37%) vs sequential (55%)
[84]Retrospective100, stages IIIA-B 95%, II 5%. ECOG 0/155 Gy (20 fx 2.75 Gy)Concurrent: Cisplatin 20 mg/m2 days 1-4 and 16-19 RT and vinorelbine 15 mg/m2 days 1, 6, 15, 20 and 2 cycles post RT/ChTOS 2 yr 58%. PFS 2 yr 49%Esophagitis G3/4 14%. Pneumonitis G3/4 4%