Margriet Kwint

General discussion and future perspectives 151 8 Table 1: Overview of studies with dose escalation using isotoxic planning strategy without extending the overall treatment time. All dose values are expressed in Gy, AE acute esophagitis, AT acute toxicity, CCRT concurrent chemoradiation, D/Fx dose/fractions, Fx fractions, OTT overall treatment time, LRC local regional control, LT late toxicity, MLD mean lung dose, N number, NR not reported, OS overall survival, RILT radiation induced lung toxicity, RT radiotherapy, seq CRT sequential chemoradiation, TD total dose, Y year Author year (ref) Study type Dose Es- calation Method Dose limiting parameters Stage N TD (Gy) Fx D/Fx OTT Primairy end- point Outcome (%) Toxicity Van Baard- wi- jk2010 (19) Prospec- tive single arm Isotoxic, Plan- ning-CT + PET-CT MLD max 19Gy, Spinal Cord Dmax 54Gy, Great Vessels or Bronchi Dmax 70.2 Gy, Brachial Plexus Dmax 66Gy I & II inoperable and III, Seq CRT 166 50.4- 79.2 28-44 1.8 (2 daily, 8h interval) 25 +/- 5.8 days OS 1y OS = 68.7 2y OS= 45 Both AT (grade 3, 21.1%; grade 4, 2.4%) and LT (grade 3, 4.2%; grade 4, 1.8%) were accept- able. Van Baard- wijk 2012 (18) Phase II Isotoxic, Plan- ning-CT + PET-CT MLD max 19Gy, Spinal Cord Dmax 54Gy, Brachial Plexus Dmax 66Gy, cen- tral structures 74Gy Stage III (Stage II n=1) CCRT 137 51-69 33-42 1.5-2.0 1.5 Gy frac- tions daily up to 45 Gy 8-h interval, followed by 1 daily fractions of 2 Gy 35 +/- 5.7 days OS 2y OS=52.4 ≥grade 3 AT 35.8%, of which AE in 25.5%. ≥3 grade LT 7.3%