Fenwick, John D, Landau, David B, Baker, Angela T, Bates, Andrew T, Eswar, Chinnamani, Garcia-Alonso, Angel, Harden, Susan V, Illsley, Marianne C, Laurence, Virginia, Malik, Zafar et al (show 11 more authors)
(2020)
Long-Term Results from the IDEAL-CRT Phase 1/2 Trial of Isotoxically Dose-Escalated Radiation Therapy and Concurrent Chemotherapy for Stage II/III Non-small Cell Lung Cancer.
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 106 (4).
pp. 733-742.
Abstract
Purpose: The IDEAL-CRT phase 1/2 multicenter trial of isotoxically dose-escalated concurrent chemoradiation for stage II/III non-small cell lung cancer investigated two 30-fraction schedules of 5 and 6 weeks' duration. We report toxicity, tumor response, progression-free survival (PFS), and overall survival (OS) for both schedules, with long-term follow-up for the 6-week schedule. Methods and Materials: Patients received isotoxically individualized tumor radiation doses of 63 to 71 Gy in 5 weeks or 63 to 73 Gy in 6 weeks, delivered concurrently with 2 cycles of cisplatin and vinorelbine. Eligibility criteria were the same for both schedules. Results: One-hundred twenty patients (6% stage IIB, 68% IIIA, 26% IIIB, 1% IV) were recruited from 9 UK centers, 118 starting treatment. Median prescribed doses were 64.5 and 67.6 Gy for the 36 and 82 patients treated using the 5- and 6-week schedules. Grade >= 3 pneumonitis and early esophagitis rates were 3.4% and 5.9% overall and similar for each schedule individually. Late grade 2 esophageal toxicity occurred in 11.1% and 17.1% of 5- and 6-week patients. Grade >= 4 adverse events occurred in 17 (20.7%) 6-week patients but no 5-week patients. Four adverse events were grade 5, with 2 considered radiation therapy related. After median follow-up of 51.8 and 26.4 months for the 6- and 5-week schedules, median OS was 41.2 and 22.1 months, respectively, and median PFS was 21.1 and 8.0 months. In exploratory analyses, OS was significantly associated with schedule (hazard ratio [HR], 0.56; 95% confidence interval [CI], 0.32-0.98; P = .04) and fractional clinical/internal target volume receiving >= 95% of the prescribed dose (HR, 0.88; 95% CI, 0.77-1.00; P = .05). PFS was also significantly associated with schedule (HR, 0.53; 95% CI, 0.33-0.86; P = .01). Conclusions: Toxicity in IDEAL-CRT was acceptable. Survival was promising for 6-week patients and significantly longer than for 5-week patients. Survival might be further lengthened by following the 6-week schedule with an immune agent, motivating further study of such combined optimized treatments.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Humans, Carcinoma, Non-Small-Cell Lung, Lung Neoplasms, Neoplasm Staging, Treatment Outcome, Dose-Response Relationship, Radiation, Time Factors, Adult, Aged, Aged, 80 and over, Middle Aged, Female, Male, Chemoradiotherapy, Dose Fractionation, Radiation |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 02 Mar 2020 11:57 |
| Last Modified: | 19 Jan 2023 00:00 |
| DOI: | 10.1016/j.ijrobp.2019.11.397 |
| Open Access URL: | https://www.redjournal.org/article/S0360-3016(19)3... |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3076585 |
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