Radiobiological determination of dose escalation and normal tissue toxicity in definitive chemoradiation therapy for esophageal cancer

Samantha Warren, Mike Partridge, Rhys Carrington, Chris Hurt, Thomas Crosby, Maria A Hawkins, Samantha Warren, Mike Partridge, Rhys Carrington, Chris Hurt, Thomas Crosby, Maria A Hawkins

Abstract

Purpose: This study investigated the trade-off in tumor coverage and organ-at-risk sparing when applying dose escalation for concurrent chemoradiation therapy (CRT) of mid-esophageal cancer, using radiobiological modeling to estimate local control and normal tissue toxicity.

Methods and materials: Twenty-one patients with mid-esophageal cancer were selected from the SCOPE1 database (International Standard Randomised Controlled Trials number 47718479), with a mean planning target volume (PTV) of 327 cm(3). A boost volume, PTV2 (GTV + 0.5 cm margin), was created. Radiobiological modeling of tumor control probability (TCP) estimated the dose required for a clinically significant (+20%) increase in local control as 62.5 Gy/25 fractions. A RapidArc (RA) plan with a simultaneously integrated boost (SIB) to PTV2 (RA62.5) was compared to a standard dose plan of 50 Gy/25 fractions (RA50). Dose-volume metrics and estimates of normal tissue complication probability (NTCP) for heart and lungs were compared.

Results: Clinically acceptable dose escalation was feasible for 16 of 21 patients, with significant gains (>18%) in tumor control from 38.2% (RA50) to 56.3% (RA62.5), and only a small increase in predicted toxicity: median heart NTCP 4.4% (RA50) versus 5.6% (RA62.5) P<.001 and median lung NTCP 6.5% (RA50) versus 7.5% (RA62.5) P<.001.

Conclusions: Dose escalation to the GTV to improve local control is possible when overlap between PTV and organ-at-risk (<8% heart volume and <2.5% lung volume overlap for this study) generates only negligible increase in lung or heart toxicity. These predictions from radiobiological modeling should be tested in future clinical trials.

Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Figures

Fig. 1
Fig. 1
(a) Lung V20Gy values for each patient in order of increasing PTV size for plans RA50 (black bars) and RA62.5 (gray bars). The dose-volume constraint of 25% is shown as a dashed line. (b) Lung NTCP was calculated using the model parameters of De Jaeger for plans RA50 (black bars) and RA62.5 (gray bars) for each patient. NTCP = normal tissue complication probability; PTV = planning target volume; RA50 = RapidArc plan to 50 Gy; RA62.5 = RapidArc plan with boost to 62.5 Gy; V20Gy = volume receiving 20 Gy.
Fig. 2
Fig. 2
(a) Mean heart dose (Gy) for each patient for plans using RA50 (black bars) and RA62.5 (gray bars). The dose-volume constraint of 25 Gy is shown as a dashed line; (b) predicted heart NTCP for each patient using the whole heart contour and the NTCP model from Gagliardi et al . NTCP = normal tissue complication probability; RA50 = RapidArc plan to 50 Gy; RA62.5 = RapidArc plan with boost to 62.5 Gy.

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