IDEAL-CRT: A Phase 1/2 Trial of Isotoxic Dose-Escalated Radiation Therapy and Concurrent Chemotherapy in Patients With Stage II/III Non-Small Cell Lung Cancer.
To report toxicity and early survival data for IDEAL-CRT, a trial of dose-escalated concurrent chemoradiotherapy (CRT) for non-small cell lung cancer.



Patients received tumor doses of 63 to 73 Gy in 30 once-daily fractions over 6 weeks with 2 concurrent cycles of cisplatin and vinorelbine. They were assigned to 1 of 2 groups according to esophageal dose. In group 1, tumor doses were determined by an experimental constraint on maximum esophageal dose, which was escalated following a 6 + 6 design from 65 Gy through 68 Gy to 71 Gy, allowing an esophageal maximum tolerated dose to be determined from early and late toxicities. Tumor doses for group 2 patients were determined by other tissue constraints, often lung. Overall survival, progression-free survival, tumor response, and toxicity were evaluated for both groups combined.



Eight centers recruited 84 patients: 13, 12, and 10, respectively, in the 65-Gy, 68-Gy, and 71-Gy cohorts of group 1; and 49 in group 2. The mean prescribed tumor dose was 67.7 Gy. Five grade 3 esophagitis and 3 grade 3 pneumonitis events were observed across both groups. After 1 fatal esophageal perforation in the 71-Gy cohort, 68 Gy was declared the esophageal maximum tolerated dose. With a median follow-up of 35 months, median overall survival was 36.9 months, and overall survival and progression-free survival were 87.8% and 72.0%, respectively, at 1 year and 68.0% and 48.5% at 2 years.



IDEAL-CRT achieved significant treatment intensification with acceptable toxicity and promising survival. The isotoxic design allowed the esophageal maximum tolerated dose to be identified from relatively few patients.
Guy's & St. Thomas' NHS Trust, King's College London, London, United Kingdom. Electronic address: david.landau@kcl.ac.uk.
David B
DB
Landau
Cancer Research UK and UCL Cancer Trials Centre, London, United Kingdom.
Laura
L
Hughes
Clatterbridge Cancer Centre, Bebington, United Kingdom.
Angela
A
Baker
Southampton General Hospital, Southampton, United Kingdom.
Andrew T
AT
Bates
Poole Hospital, Poole, United Kingdom.
Michael C
MC
Bayne
Cancer Research UK and UCL Cancer Trials Centre, London, United Kingdom.
Nicholas
N
Counsell
North Wales Cancer Centre, Rhyl, United Kingdom.
Angel
A
Garcia-Alonso
Addenbrookes Hospital, Cambridge, United Kingdom.
Susan V
SV
Harden
Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom.
Jonathan D
JD
Hicks
Guy's & St. Thomas' NHS Trust, King's College London, London, United Kingdom.
Simon R
SR
Hughes
Royal Surrey County Hospital, Guilford, United Kingdom.
Marianne C
MC
Illsley
Cancer Research UK and UCL Cancer Trials Centre, London, United Kingdom.
Iftekhar
I
Khan
Poole Hospital, Poole, United Kingdom.
Virginia
V
Laurence
Clatterbridge Cancer Centre, Bebington, United Kingdom.
Zafar
Z
Malik
Clatterbridge Cancer Centre, Bebington, United Kingdom.
Helen
H
Mayles
Clatterbridge Cancer Centre, Bebington, United Kingdom.
William Philip M
WPM
Mayles
Mount Vernon Hospital, Middlesex, United Kingdom.
Elizabeth
E
Miles
Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom.
Nazia
N
Mohammed
Cancer Research UK and UCL Cancer Trials Centre, London, United Kingdom.
Yenting
Y
Ngai
Mount Vernon Hospital, Middlesex, United Kingdom.
Emma
E
Parsons
Guy's & St. Thomas' NHS Trust, King's College London, London, United Kingdom.
James
J
Spicer
St. Bartholomew's Hospital, London, United Kingdom.
Paula
P
Wells
Mount Vernon Hospital, Middlesex, United Kingdom.
Dean
D
Wilkinson
University of Oxford, Oxford, United Kingdom.
John D
JD
Fenwick
D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000401:mortality* / Q000473:pathology / Q000628:therapy*; D059248:Chemoradiotherapy / Q000401:mortality*; D015897:Comorbidity; D019583:Dose Fractionation, Radiation; D004307:Dose-Response Relationship, Radiation; D064420:Drug-Related Side Effects and Adverse Reactions / Q000401:mortality*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000401:mortality* / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D015995:Prevalence; D011832:Radiation Injuries / Q000401:mortality*; D015996:Survival Rate; D016896:Treatment Outcome