ESTRO 2020

Session Item

Poster highlights 21 PH: Predictive modelling
Poster Highlights
14:31 - 14:39
Can we dose escalate in anal cancer without an increase in dose to OARs?
Natalie Abbott, United Kingdom


Can we dose escalate in anal cancer without an increase in dose to OARs?
Authors: Natalie Abbott.(RTTQA group- Velindre Cancer Centre, Medical Physics, Cardiff, United Kingdom), Richard Adams.(Cardiff University Department of Cancer & Genetics, and Velindre Cancer Centre, Cardiff, United Kingdom), Joanne Copeland.(Leeds University, Leeds Clinical Trials Research Unit, Leeds, United Kingdom), Mark Harrison.(Mount Vernon Hospital, Mount Vernon Centre for Cancer, Northwood, United Kingdom), Maria Hawkins.(University College London, UcL, London, United Kingdom), Rebecca Muirhead.(Oxford University Hospitals NHS Trust, o, Oxford, United Kingdom), Maxwell Robinson.(Oxford University Hospitals NHS Trust, o, Oxford, United Kingdom), David Sebag-Montefiore.(St James University Hospital, Leeds Cancer Centre, Leeds, United Kingdom)
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Purpose or Objective

PersonaLising Anal cancer radiotherapy dOse (PLATO) is an integrated protocol, including anal cancer trial 5 (ACT5) for high risk patients.

ACT5 is a randomised trial comparing UK standard and dose escalated concurrent chemo-radiotherapy. Dose escalation above UK standard dose [1] is to a PTV_Boost encompassing primary disease and positive nodes plus a 5mm margin. A pilot study of 60 patients was carried out across 12 UK sites. This was to allow for planned interim analysis of acute toxicity [2], protocol compliance, and to determine if there is a significant increase to OAR dose metrics associated with dose escalation.

Dose escalation was as below

* Standard arm: PTV_Boost n/a

* Dose escalation arm1: PTV_Boost 58.8 Gy in 28#

* Dose escalation arm2: PTV_Boost 61.6 Gy in 28#

We present statistical analysis of trial OAR dose metrics, comparing the dose escalation arms with standard dose treatments to determine if a statistically significant increase is seen in OAR dose metrics.

Material and Methods

58 patients were evaluable in the ACT5 pilot phase from 12 UK sites. Patients were randomised as below.

* Standard arm: 18 patients

* Dose escalation arm1: 21 patients

* Dose escalation arm2: 19 patients

All patients had a prospective RTQA of contouring and planning to ensure compliance with protocol and review of OAR dose constraints.

Trial OAR dose metrics were compared in both dose escalation arms to those in the standard dose arm using the Mann-Whitney U test.


There was no statistically significant increase in any OAR dose metric apart from genitalia D5% and Femoral Heads D5%. A statistically significant difference was seen for D5% genitalia in both dose escalation arms, see Table 1.

For the genitalia, one arm1 and one arm2 patient did not meet the mandatory trial dose constraints, with a total of 22 patients meeting mandatory but not optimal constraints. This was due to overlap with PTV_Boost in both cases, with both plans considered optimal and acceptable for clinical use.

For the femoral heads, although there is a statistically significant increase in dose for D5% for arm2, all values were within the optimal constraint, D5%<50Gy, with a larger standard deviation seen for the standard arm, 2.3 vs 6.3 (arm2 vs standard: min 29.1Gy-7.7Gy, max 38.0Gy-42.7Gy, mean 34.3Gy-34.0Gy).


Dose escalation to primary disease and node positive disease is achievable without a statistically significant increase in the vast majority of OAR dose constraints. There was a statistically significant increase in small volume dose to genitalia due to the potential for overlap with PTV boost volumes.


[1] R. Muirhead,,”National Guidance for IMRT in anal cancer,” v3,18.04.2016

[2] A. Gilbert,, “Pre-specified pilot analysis of a randomised pilot/phase II/III trial comparing standard dose vs dose-escalated concurrent CRT in anal cancer (PLATO-ACT5)”, ESMO Congress,2019