Margriet Kwint

Chapter 8 152 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 Cannon 2013 (15) Phase I Prospec- tive single arm Stratified risk Plan- ning-CT +/- PET- CT A Bayesian dose-escalation scheme incorpo- rating predicted risk for pneumo- nitis, were sub- sequent patient were grouped in risk bins All stages eligible Stage I/II =9%, Stage III = 71% Stage IV = 13%, Recurrent =8% RT and seq CRT 75 57.0- 85.5 25 2.28- 3.42 5 weeks (33 days) Maxi- mum tolerated dose 2y LRC= 62 3y OS= 29 No grade 3 AT and LT, Grade 4 and 5 LT in 8%. The maximum tolerated dose was identified at 63.25 Gy /25 Fx Kong 2017 (16) Phase II, Prospec- tive sin- gle arm Isotoxic Plan- ning-CT + Mid treat- ment FDG-PET RILT grade 2 Inoperable/ irresec-table NSCLC stage I-III (90% stage III) CCRT (93%) and RT 42 63-86 30 2.1 – 2.8 6 weeks (40 days) OS, LRC 2y LRC= 82 2y OS= 52 5y OS=30 Grade 3: esoph- agitis 12% , RILT 7% and cardiac toxicity 2% Landau 2016 (17) Phase I/II Isotoxic Plan- ning-CT Split into 2 Group1: an escalating esophageal dose constraint Group2: Lung and other nor- mal tissue dose constraints Stage II & III CCRT 82 63-73 30 2.1 – 2.4 6 weeks (40 days) Toxicity 1y OS=88 2y OS= 68 6% grade 3 AE, 4% grade 3 pneumonitis. 1 grade 5 esopha- geal perforation. 68Gy was de- clared esopha- geal maximum tolerated dose.