ESTRO 36 Abstract Book

S152

ESTRO 36 2017

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room for quality improvement in this increasingly

influential research area.

SP-0297 Method of development of ESMO Magnitude of

Clinical Benefit applicable for radiotherapy?

E.G.E. De Vries

, R. Sullivan

, N.I. Cherny

UMCG University Medical Center Groningen,

Department of Medical Oncology, Groningen, The

Netherlands

Institute of Cancer Policy, Kings Health Partners

Integrated Cancer Centre- King's College London,

London, United Kingdom

Shaare Zedek Medical Center, Cancer Pain and Palliative

Medicine Service- Department of Medical Oncology,

Jerusalem, Israel

The value of any new therapeutic strategy or treatment is

determined by the magnitude of its clinical benefit

balanced against its cost. Evidence for clinical benefit

from new treatment options is derived from clinical

research, in particular phase III randomised trials, which

generate unbiased data regarding the efficacy, benefit

and safety of new therapeutic approaches. Until recently,

there was no standard tool for grading the magnitude of

clinical benefit of cancer therapies, which may range from

trivial (median progression-free survival advantage of only

a few weeks) to substantial (improved long-term survival).

Indeed, in the absence of a standardised approach for

grading the magnitude of clinical benefit, conclusions and

recommendations derived from studies are often hotly

disputed and very modest incremental advances have

often been presented, discussed and promoted as major

advances or 'breakthroughs'. Recognising the importance

of presenting clear and unbiased statements regarding the

magnitude of the clinical benefit from new therapeutic

approaches derived from high-quality clinical trials, the

European Society for Medical Oncology (ESMO) has

developed a validated and reproducible tool to assess the

magnitude of clinical benefit for cancer medicines, the

ESMO Magnitude of Clinical Benefit Scale (ESMO-MCBS).

An ESMO Task Force to guide the development of the

grading scale was established in March 2013. A first-

generation draft scale was developed and adapted through

a ‘snowball’ method based upon previous work of Task

Force members who had independently developed

preliminary models of clinical benefit grading. The first-

generation scale was sent for review by 276 members of

the ESMO faculty and a team of 51 expert biostatisticians.

The second-generation draft was formulated based on the

feedback from faculty and biostatisticians and the

conceptual work of Alberto Sobrero regarding the

integration of both hazard ratio (HR), prognosis and

absolute differences in data interpretation [J Clin Oncol

2009, Clin Cancer Res 2015]. The second-generation draft

was applied in a wide range of contemporary and historical

disease settings by members of the ESMO-MCBS Task

Force, the ESMO Guidelines Committee and a range of

invited experts. Results were scrutinized for face validity,

coherence and consistency. Where deficiencies were

observed or reported, targeted modifications were

implemented and the process of field testing and review

was repeated. This process was repeated through 13

redrafts of the scale preceding the current one (ESMO-

MCBS v1.0). The final version and fielded testing results

were reviewed by selected members of the ESMO faculty

and the ESMO Executive Board. Version 1.0 appeared in

2015 (Cherny et al. Ann Oncol).

This tool thus provides a rational, structured and

consistent approach to derive a relative ranking of the

magnitude of clinically meaningful benefit that can be

expected from a new anti-cancer treatment. The ESMO-

MCBS is an important first step to the critical public policy

issue of value in cancer care, helping to frame the

appropriate use of limited public and personal resources

to deliver cost-effective and affordable cancer care. The

ESMO-MCBS is a dynamic tool and its criteria will be

revised on a regular basis. The next version will include

also an approach to grade the clinical benefit data derived

from the registration trials of medications approved on the

basis of these single arm studies. Currently the grading of

newly registered drugs is included in ESMO-guidelines.

A similar approach to develop a scale can potentially be

used for other treatment or diagnostic areas in oncology

including radiotherapy. For a scale grading radiotherapy,

there will likely be a number of similarities and

differences versus a scale for drug treatment. Factors

taken into account for the radiotherapy scale might well

include the adjuvant and curative outcomes: overall

survival, disease free survival, local recurrence free

survival, pathological complete response and non-

curative/palliative outcomes such as: single symptom

relief (complete response, partial response, relief

duration of response), control of hemorrhage, relief of

obstruction, effects on skeletal events (pain, fracture) and

neurological function. We anticipate methodological

challenges in the relative weighting and scoring of

palliative outcomes form localized radiotherapy as

distinct from systemic therapies.

Debate: This house believes that proton guided photons

(online MR guided therapy) will be superior to photon

guided protons (CBCT proton therapy)

SP-0298 For the motion

B. Raaymakers

UMC Utrecht, Department of Radiation Oncology,

Utrecht, The Netherlands

The common ground for proton and photon guidance, that

is MRI and CBCT guidance, is the desire to localize the

target and the surrounding structures in order to improve

the spatial accuracy of dose delivery. This is especially

important to better target and to minimize the high dose

volumes which are leading to the most acute toxicity and

are often dose limiting.

With modern accelerators, both proton- and photon

therapy can generate a conformal high dose volume, while

image guidance is the most important parameter on

delivering this high dose volume to the correct position

and with that minimize this high dose volume. Doing

so, also hypo-fractionated treatments for more and more

tumor sites can become feasible.

MRI guidance is superior because:

1) Soft-tissue guidance of MRI will out-perform CBCT

based set-up

2) MRI provides dynamic imaging to track breathing and

peristalsis without the need for retrospective binning

3) MRI enables daily full re-planning

4) MRI provides intra-fraction (volumetric) imaging for

dose reconstruction and plan adaptation

5) Integrated MRI provides functional response assessment

during the course of radiotherapy

CBCT has greatly improved radiotherapy by offering 3D

imaging just prior to radiation delivery, these images can

be used for improved patient set up and assessment of the

breathing pattern. These data, even though they have

limited soft-tissue contrast, are acquired just prior to

treatment. Using these instead of relying on pre-

treatment images of days (if not weeks) old, provides

much more representative information on the target and

surrounding structures and will improve patient set-up.

With MRI integrated in the radiotherapy system, all the

aims from CBCT guidance can be brought to the next level.

MRI offers soft-tissue contrast, so one can much better

distinguish tumor from surrounding tissues. Also dynamic

MRI can provide 4D anatomical data with high temporal

resolution (e.g. 3Hz) to detect breathing and peristaltic