ESTRO 36 Abstract Book

S250

ESTRO 36

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The role of radiotherapy in pancreatic ductal

adenocarcinoma (PDAC) remains controversial. In contrast

to the notion that all patients with PDAC die of metastatic

disease, at least a 20% suffer and die from local

recurrence. The latter provides a strong rationale for

improving local control using radiotherapy, including dose

escalation with SBRT. The advent of modern RT and

imaging technology can reduce toxicity without

compromising efficacy. International consensus on the

definition of R1-resection in primarily and borderline

resectable PDAC is needed to better define radiotherapy

indications. SBRT and chemoradiotherapy (CRT) have to

be tested in the context of more efficient chemotherapy

regimens, such as FOLFIRINOX and Gemcitabine/Nab-

paclitaxel if it is to unmask the importance of improved

local control. The development of molecular signatures to

differentiate patients with high risk of developing only

local recurrence from those likely to die of distant

metastases is urgently needed. Preclinical and

patient

data

indicate

testing

the

efficacy

of immunotherapeutics in combination with (C)RT in

future clinical trials.

SP-0471 Standard treatment in anal cancer: where do

we stand and where should we go?

R. Muirhead

CRUK/MRC Oxford Institute for Radiation Oncology,

Oncology, Oxford, United Kingdom

Introduction - Anal cancer is a rare disease but the

incidence is increasing rapidly. Despite its rarity there is

significant research, development and interest in this

topic with large phase III trials involving hundreds of

patients’ completed, and literature on anal

cancer regularly on the “most read” list of radiotherapy

journals. The initial phase III trials investigated the use of

concurrent chemotherapy with radiotherapy, confirming

the benefit of concurrent chemoradiotherapy using

Mitomycin and Fluorouracil. These trials changed the

standard treatment in anal cancer from APR with

permanent stoma to CRT. Subsequent phase III trials have

investigated diverse concurrent chemotherapy regimens

and the different settings of systemic therapy; namely the

role of neo-adjuvant and adjuvant chemotherapy and

different concurrent regimens. However these strategies

failed to demonstrate significant impact on outcome, and

the optimal concurrent regimen remains Mitomycin and

Fluorouracil. The ESMO-ESSO-ESTRO and NCCN guidelines

support the use of capecitabine as an alternative to

fluorouracil, however phase III evidence supporting this

recommendation is not available. The phase I and II

studies, multicentre and single centre data supporting this

regimen, highlight the different toxicity profiles. Due to a

failure to demonstrate improved outcomes in recent phase

III trials investigating different systemic strategies,

moving forward we will need to consider how improving

the radiotherapy component of our treatment can improve

both cancer outcomes and the late toxicity of this toxic

but effective treatment.

Radiotherapy Technique - The RTOG 0529, a phase II study

investigating the acute toxicity of IMRT in comparison to

the historical RTOG 9811, raised some important questions

regarding the challenges of implementation of IMRT in

anal cancer. The central review of volumes revealed a

large numbers of revisions required in contouring. In

addition there is a correlation between plans that fail to

meet the recommended dose constraints and G3 toxicity.

In implementing IMRT, thought has to be given to volumes

to be included, doses and fractionations, margins used and

organ at risk constraints; each of these issues alongside

the relevant literature will be discussed in the context of

designing the UK IMRT guidance.

Late toxicity and Quality of Life – Until recently there was

minimal literature on the late toxicity of this treatment

despite cure rates of >70%. With the requirement to

quantify late toxicity in order to design studies to improve

morbidity and increasing awareness of cancer

survivorship; there is renewed interest in this topic. A

number of recent series have reported the late toxicity

following IMRT using a combination of physician recorded

and patient reported outcome measures. While there is

recovery of the majority of acute side effects and quality

of life 3 months after completing treatment, diarrhoea,

urinary incontinence and dyspareunia persisted beyond 1

year. These adverse effects were reported following

"modern" CRT techniques therefore it is arguable that to

see an improvement in these outcomes, we will need to

explore individualising treatment dose to minimise late

effects.

RT stratification according to stage – Although there has

always been much interest in increasing doses with

external beam or brachytherapy boosts in all stages of anal

cancer until recently there was no dose response data

available. The RTOG 0529 study set a precedence for

stratifying dose delivered according to tumour stage. This

lecture will discuss the dose response model which reports

while there was a dose response in both early and locally

advanced stages of tumour, the improved local control

rates achieved by dose escalating in locally advanced

tumours far exceeds what can be achieved by dose

escalating in early tumours.

Future international trials - The UK led PLATO study trial

(ISRCTN88455282) is funded by Cancer Research UK and

incorporates many of the themes of the teaching lecture.

PLATO is a unique “umbrella” trial addressing a number of

radiotherapy questions in the loco-regional management

of anal cancer. It incorporates 3 individual trials: ACT3 -

for T1N0 anal margin tumours, evaluating a strategy of

selective reduced dose chemoradiotherapy after local

excision, within a single arm phase II trial; ACT4 – for T1-

2 N0 (≤4cm) tumours, evaluating reduced dose

chemoradiotherapy to the primary tumour, in a

randomised 2:1 phase II study, with the aim of reducing

toxicity and maintaining efficacy; ACT5 – for T2 N1-3, T3/4

Nany, evaluating dose escalation within a seamless

randomised trial design moving from pilot to phase II to

phase III, with the aim of reducing locoregional failure.

The primary endpoint for all 3 trials is 3 year local regional

failure, key secondary outcomes will focus on patient

reported outcome measures.

Joint Symposium: ESTRO-RANZCR: Big data to better

radiotherapy

SP-0472 The pros, cons, process and challenges for

achieving better radiotherapy through data -an

introduction

L.C. Holloway

1,2,3,4

Ingham Institute and Liverpool and Macarthur Cancer

Therapy Centres, Medical Physics, Sydney, Australia

University of Wollongong, Centre for Medical Radiation

Physics, Wollongong, Australia

University of Sydney, Institute of Medical Physics,

Sydney, Australia

University of New South Wales, South West Sydney

Clinical School, Sydney, Australia

The magnitude and use of data is expanding in many areas

including medicine. The opportunities for using data to

improve our knowledge and understanding are many and

varied including demographic, disease and outcome

investigations. Within current radiotherapy practice data

may be collected in a very rigorous approach within for

instance a clinical trial framework and data is also

collected in an ongoing fashion during standard clinical

practice. It is possible for us to gain knowledge from both

rigorously collected data and clinical practice data.

The gold standard of randomised clinical trial (RCT)