Session Speaker

Is 7-Day-a-Week (weekends-in) Accelerated Radiotherapy Beneficial for Locally Advanced Head & Neck Cancer: Results of Two Single-Institution Clinical Trials (CAIR-1 and CAIR-2)
Boguslaw Maciejewski, Krzysztof Skladowski
Poland

Objectives and Purpose: In radiotherapy rapid repopulation neutralizes a part of cell kill effect and therefore decreases treatment efficacy. Many clinical trials on altered dose fractionation showed only moderate therapeutic benefit because of heterogeneity of patients and fractionation characteristics using 5 days/week regimens.

Aim of two Polish trials (CAIR-1 and CAIR-2) carried out in a single institution was to answer whether Continuous Accelerated Irradiation (CAIR) in 7days/week (weekends-in) can improve tumour control and survival of patients with locally advanced head and neck cancer.

Materials and Methods: There were 100 pts recruited into CAIR-1 and 345 pts into CAIR-2 trials, all with T2-4N0-1 oral cavity, oropharyngeal and supraglottic cancer with no prior treatment. All cases were well randomized and stratified.

Radiotherapy: CAIR-1: arm(A) of 51 pts (7fx/7d) - 70Gy in 35 fx in 35d (fx-fraction, d-days); control arm (B) of 49 pts (5fx/7d) - 70Gy in 35fx in 49d. Patients were irradiated, regulatory including weekends (arm A) or only during working days (arm B). The only variable was treatment time (OTT) longer by 14 days in arm (A) than in arm (B).

CAIR-2: aimed to answer whether it is possible achieve the same benefit of 7fx/7d but using 7fx/5d (concomitant boost - CB). Arm (A-CB) of 173 pts (7fx/5d) - 72Gy in 40 fx in 40d (weekends-off). Arm (B-CAIR) of 172 pts (7fx/7d) - 72Gy in 40fx in 40 d (weekends-in). The only variable was dose intensity: 2 fractions daily was given on Tues-Fri instead Sat-Sun.

Results: In CAIR-1: 5-year locoregional control (LRC) was significantly higher in favour of 7fx/7d (75% vs. 33%) and DFS and OS as well (58% vs. 19%, 63% vs. 20%). Because of such high LRC, for ethical reason trial was closed earlier than planned. Acute mucosal confluent mucositis (CM) were more severe and frequent in arm A (90%) than in arm B (73%). When the CM was scored once-a-week instead of trice-a-week about 35% of the CM events were missed. Ratio of late compli cations III° was low in both arms (4%).

In CAIR-2: 5-year LRC did not differ in arm CB from arm CAIR (68% vs. 65%), and DFS as well, OS was slightly better in the CB (55%) than in CAIR (48%). Incidence of acute CM was almost the same in both arm (78%-CB, 80%-CAIR) and late complications III° occurred also in similar rate (~5%).

Conclusions: For locally advanced H&N cancer, significant benefit in LRC, DFS and OS can be achieved shortening OTT by 2 weeks using standard 1.8Gy fractions 7days/week (weekends-in) with no change in total dose. However, Concomitant Boost with 2 daily fractions of 1.8Gy during working days (weekends-off) with OTT shortened by 2 weeks and unchanged total dose also provides almost the same benefit as 7 fx/7d regimen (CAIR). Acute confluent mucositis is wave-like event rather than tri-phasic as it is generally accepted till now. Therefore precise quantitation of the CM in daily practice, needs regular and frequent (at least twice-a-day) scoring, otherwise severity and incidence of the CM can be seriously underestimated.