148 Dose escalation in the I-START trial – ISoToxic Accelerated RadioTherapy in locally advanced non-small cell lung cancer

Normal tissue considerations and dose–volume constraints in the moderately hypofractionated treatment of non-small cell lung cancer

“…V 20Gy (% volume receiving 20 Gy) <30-35% is commonly used in conventional fractionation [24] and many of the studies analysed here have used this metric without accounting for differences in fraction number, fraction size or dose distribution due to delivery technique [8]. A number of the studies use a mean lung dose (MLD) constraint as detailed in the QUANTEC report [16], with five utilising a LQ (linear quadratic) correction on the DVH (dosevolume histogram) before generating a MLD or rNTD mean (mean fraction-normalised lung dose divided by the normalised prescription dose) [13,14,[25][26][27]. In three studies the lung dose is the basis for deciding the prescription dose level [26][27][28].…”

“…None of the clinical studies reviewed applied a constraint to the brachial plexus but three of the trial protocols did. I-START imposed D 1cc < 55 Gy/20# [13], while IDEAL-CRT utilised both D 0.1cc < 65 Gy/30# and D 30% < 60 Gy/30# [14], these correspond to EQD 2 limits of D 1cc < 65.3 Gy 2 , D 0.1cc < 67.7 Gy 2 and D 30% < 60 Gy 2 respectively. As RTOG 11-06 is a 2-phase regime an EQD 2 correction of D 0.03cc < 63 Gy is not appropriate.…”

“…A summary of the heart data gathered is included in the Supplementary material. There is considerable heterogeneity in the DVCs applied: from maximum dose [12,15], to mean heart dose [12,25], to minimum dose [13,14,28]. Late heart toxicity tends not to be reported in the NSCLC literature, perhaps a reflection of the time taken for it to develop and poor overall survival in this patient population.…”

“…A similar study in a concurrent chemotherapy setting established a MTD of 69 Gy/23# (EQD 2 = 70Gy 3 , 56.58 Gy/20#) [35]. I-START have stratified dose escalation groups according to the length of oesophagus within the PTV (planning target volume) [13]. Chen et al utilised LQ corrected DVHs in their dosimetric analysis and reported values in terms of EQD 2 (acute: a/b = 10, late: a/b = 3).…”

“…Long term follow-up of this schedule has shown local tumour control at 3 years of 74.1% [11]. There are a number of current trials in hypofractionated NSCLC treatment, including RTOG 11-06 (30#) [12], I-START (20#) [13] and IDEAL-CRT (30#) [14], while the results of NCIC CTG BR.25 (60 Gy/15#) have recently been published [15].…”