Angela Baker

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

Purpose 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 and Methods 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. Results 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. Conclusions 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.

A multicentre study of the evidence for customized margins in photon breast boost radiotherapy

Objective: To determine if subsets of patients may benefit from smaller or larger margins when using laser setup and bony anatomy verification of breast tumour bed (TB) boost radiotherapy (RT). Methods: Verification imaging data acquired using cone-beam CT, megavoltage CT or two-dimensional kilovoltage imaging on 218 patients were used (1574 images). TB setup errors for laser-only setup (dlaser) and for bony anatomy verification (dbone) were determined using clips implanted into the TB as a gold standard for the TB position. Cases were grouped by centre-, patient- and treatment-related factors, including breast volume, TB position, seroma visibility and surgical technique. Systematic (Σ) and random (σ) TB setup errors were compared between groups, and TB planning target volume margins (MTB) were calculated. Results: For the study population, Σlaser was between 2.8 and 3.4 mm, and Σbone was between 2.2 and 2.6 mm, respectively. Females with larger breasts (p = 0.03), easily visible seroma (p ≤ 0.02) and open surgical technique (p ≤ 0.04) had larger Σlaser. Σbone was larger for females with larger breasts (p = 0.02) and lateral tumours (p = 0.04). Females with medial tumours (p < 0.01) had smaller Σbone. Conclusion: If clips are not used, margins should be 8 and 10 mm for bony anatomy verification and laser setup, respectively. Individualization of TB margins may be considered based on breast volume, TB and seroma visibility. Advances in knowledge: Setup accuracy using lasers and bony anatomy is influenced by patient and treatment factors. Some patients may benefit from clip-based image guidance more than others.

A comparison of imaging schedules for prostate radiotherapy including online tracking techniques

Background and purpose: Repeat imaging protocols, specifying imaging frequency and action levels for movement correction, can be used to achieve more accurate targeting of the prostate gland during radiotherapy. We have carried out a study comparing the accuracies of online versus off-line correction strategies which use implanted marker seeds to localize the prostate. Material and methods: Data have been analysed for 60 prostate patients, verified using an online imaging technique. Systematic and random errors have been calculated for a daily imaging protocol and for other common imaging schedules. Resource requirements have been assessed for the daily imaging technique by analysing the in-room timings performed on 10 patients. Results: Daily imaging is beneficial for the majority of patients, an online imaging schedule with a 2 mm action level significantly reducing systematic and random errors. The online imaging can be performed with a 2-minute increase in the standard treatment slot. Conclusions: Online imaging tracking techniques can facilitate margin reduction, which may help to reduce rectal toxicities. The impact on departmental time and resource requirements is modest for the online daily tracking technique with marker seeds and kilovoltage planar imaging.

A new era for clinical trial quality assurance: A credentialing programme for RTT led adaptive radiotherapy

Highlights • A multi-centre QA programme incorporating adaptive plan selection has been developed.• This novel QA approach has been validated by 71 RTTs from ten UK centres.• A multidisciplinary approach is essential in the development of a credentialing programme.