ESTRO 36 Abstract Book

S52

ESTRO 36 2017

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The physical pattern of energy deposition and the

enhanced relative biological effectiveness (RBE) of

charged particles compared to photons offer unique and

not fully understood or exploited opportunities to improve

the efficacy of radiation therapy. Variations in RBE within

a pristine or spread out Bragg peak and between particle

types may be exploited to enhance cell killing in target

regions without a corresponding increase in damage to

normal tissue structures. In addition, the decreased

sensitivity of hypoxic tumors to photon-based therapies

may be partially overcome through the use of more

densely ionizing radiations. These and other differences

between particle and photon beams may be used to

generate biologically optimized treatments that reduce

normal tissue complications. In this presentation, the

biological basis of various models of RBE will be reviewed.

In addition, the impact of the RBE of charged particles on

measurable biological endpoints, treatment plan

optimization, and the prediction or retrospective

assessment of treatment outcomes will be examined. In

particular, an AAPM task group was formed to critically

examine the evidence for a spatially-variant RBE in proton

therapy. Current knowledge of proton RBE variation with

respect to proton energy, dose, and biological endpoint

will be reviewed. The clinical relevance of these

variations will be discussed. Recent work focused on

improving simulations of radiation physics and biological

response in proton, helium, and carbon ion therapy will

also be presented. In addition to the physical advantages

of protons and more massive ions over photons, the future

application of biologically optimized treatment plans has

the potential to provide higher levels of local tumor

control and improved normal tissue sparing.

SP-0108 New horizons in radiobiology: from Relative

Biological Effectiveness to “new biology”

M. Durante

University of Trento, Povo, Italy

The era of precision medicine has a strong impact on

radiotherapy. Treatment planning is now moving from

purely physical dose calculation toward biological

optimization. Several studies on biomarkers and combined

treatments are currently modifying the treatment plan

and the design of clinical trials in oncology. In particle

therapy, most of the discussion focus on the exploitation

of the RBE, which is commonly done in heavy ion therapy

and not yet in protontherapy. RBE assessment may

improve plan optimization and prevent some side effects

that seem to be related to the physical properties, both

electromagnetic and nuclear, of protons. Charged

particles can however elicit a gene response qualitatively

different from that caused by X-ray exposure, and thus

open new opportunities. The combination of particles and

immunotherapy is particularly promising.

Symposium: Imaging for therapeutic response / toxicity

evaluation

SP-0109 Functional imaging as biomarker for toxicity

response

Y. Cao

University of Michigan, Radiation Oncology - Physics,

Ann Arbor, USA

Population based models for radiation effects on normal

tissue and organ function have played a role for

minimizing risk of organ injury during treatment

planning. However, precision individualized medicine

requests to understand individual patient response and

sensitivity to radiation doses. Quantitative functional

imaging is a powerful tool to assess regional information,

and understand local response to radiation doses, which is

complementary to molecular and genetic biomarkers if

they

exist.

Our recent studies in neurotoxicity reveal a few

interesting findings. For example, a maximum dose effect

in white matter fiber bundles is found using longitudinal

diffusion tensor imaging and fiber tracking

technique. Also, gEUD doses with large α-values (e.g., 14

and 50) received in the brain are associated with late

neurocognitive declines, suggesting a maximum dose

effect on cognitive function. These results suggest that

responses of brain tissue, critical structure, and cognitive

function to radiation doses and dose distribution are more

complex than we originally thought.

Liver is another organ that is sensitive to radiation. Recent

studies show that liver function is a predominant predictor

for overall survival for patients with intrahepatic cancer

and cirrhosis regardless of intervention. Radiation effects

on the liver function have been investigated and modeled

using dynamic contrast enhanced MRI and HIDA SPECT. To

safely treat intrahepatic cancers, both regional and global

liver function measures are needed. Can a single test

provide regional and global liver function measurements

and allow for liver function management during therapy

planning? Gadoxetic-acid is widely available liver-specific

MRI contrast and is routinely used in clinical MRI. The

routine clinical MRI scans with Gadoxetic-acid that are

temporally sparse-sampled challenge quantification of

liver function using the dual-input tow-compartment

model. We have developed a robust algorithm to quantify

regional and global liver function from dynamic gadoxetic-

acid enhanced MRI. Using regional liver function maps

created by our method, we can assess the dose-response

of hepatic function in the individual patients, which can

be used for optimizing the dose distribution in the liver

and thereby minimizing risk of liver function failure. Also,

the liver function distribution quantified by this method

can be used for assessing liver function preserve by

determining the liver functional volume (LFV) for support

of clinical decision making for intrahepatic cancer

therapy.

In this presentation, recent development of imaging and

analysis techniques in brain and liver as well as

implications of new findings using the techniques will be

discussed.

SP-0110 Imaging tumour response to neoadjuvant

treatment in GI tumours

G. Meijer

UMC Utrecht, Department of Radiation Oncology,

Utrecht, The Netherlands

Trimodality treatments are often the preferred treatment

option in the curative management of cancers in the

gastrointestinal tract. Here a combined radiotherapy and

chemotherapy regimen are administered prior to the

surgical resection of the primary tumor and involved

lymph nodes. Typically the primary aim of the

neoadjuvant regimen is to downstage the tumor to

facilitate negative resection margins at surgery.

Interestingly, although these neoadjuvant treatment

regimens are not optimized for obtaining local control,

pathology reports regularly reveil a complete pathologic

response (i.e. no viable tumor left in resection specimen)

in particularly rectum and esophageal cancer patients.

This opens the window to more tailored treatments where

only patients are operated upon that really benefit from

the surgery. However, this can only be accomplished if we

have accurate means to predict the pathologic outcome

prior to surgery. Many research groups have investigated

the potential of pre-surgical clinical assessments (e.g.

biopsies, endoscopies) to predict the outcome with

moderate success. More recently, quantitative imaging

techniques like FDG-PET, dynamic contrast enhanced

(DCE) MRI, diffusion-weighted (DW) MRI, have shown more

potential.