ESTRO 36 Abstract Book

S271

ESTRO 36 2017

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DKFZ, Clinical Cooperation Unit Molecular

Radiooncology, Heidelberg, Germany

Heidelberg Ion Beam Therapy Center, HIT, Heidelberg,

Germany

Center for Heavy Ion Research GSI, Dept. of Biophysics,

Darmstadt, Germany

University Hospital of Heidelberg, Dept. of Radiation

Oncology, Heidelberg, Germany

Purpose or Objective

Proton therapy allows highly conformal treatments of

head and neck cancer due to its inverted depth-dose

profile and advanced beam delivery systems. This allows

escalating the dose while still sparing the surrounding

healthy tissue. For treatment planning in patients, a fixed

relative biological effectiveness (RBE) of 1.1 is currently

used. However, experimental

in vitro

studies indicate that

the RBE increases at the distal edge of the spread-out

Bragg peak (SOBP). This increased biological effectiveness

may either lead to detrimental side effects, especially in

the late responding normal central nervous system, or it

may compromise dose escalation in the tumor. In this

study, the potential increase of the proton RBE along the

SOBP is investigated for late reactions of rat spinal cord.

Material and Methods

The cervical spinal cord of female Sprague Dawley rats was

positioned at four different depths of a 6 cm spread-out

Bragg peak (entrance region, center and two positions at

the distal edge of the SOBP, linear energy transfer (LET):

1.45-5.60 keV/µm). Single proton doses of increasing dose

levels were applied to the segments C1-C6 of the cervical

spinal cord using a field size of 10 x 15 mm

. At each

position, complete dose-response curves were established

and the tolerance doses TD

(dose at 50% complication

probability) were determined for the clinically relevant

endpoint “development of forelimb paresis grade II within

300 days”. Based on the TD

-values, RBEs were calculated

using the tolerance doses for photons of our previous

study. Rats reaching this endpoint were sacrificed and the

spinal cord was removed and processed for histological

examinations.

Results

Preliminary evaluations of the single dose experiments

showed that the minimum and mean latency time

decrease with increasing LET. Preliminary data of the

dose-response curves confirm an RBE of 1.1 in the

entrance region (LET 1.45 keV/µm) while a further

increase of the RBE was found towards the distal edge of

the SOBP (LET 5.40 keV/µm).

Conclusion

The preliminary data of this study suggests an increased

proton RBE at the distal edge of the SOBP. Further

experiments with fractionated treatments are ongoing. If

the finding of this study is confirmed quantitatively, it

might be necessary to include the variability of the RBE in

clinical treatment planning to optimize safety and

effectiveness of proton therapy in patients.

Symposium: Patient Reported Outcomes (PROs) in

radiotherapy

SP-0518 Differences between PRO and clinician

reported morbidity and associations to clinical

outcome

K. Kirchheiner

Medical University Vienna, Dept. of Radiation Oncology,

Vienna, Austria

Patient-reported outcomes (PROs) describe any outcome

reported directly by the patient with a subjective

evaluation about disease and its treatment. PROs

summarize a wide spectrum of endpoints in the framework

of a holistic bio-psycho-social cancer care model, such as

reports on symptoms and side effects, as well as multi-

dimensional health-related quality of life, evaluation of

the perceived health and psychological status, reports

about adherence to treatment, satisfaction with

treatment, according to the US Food and Drug

Administration (FDA) and the European Medical Agency

(EMA). In contrary to the physician assessed morbidity

grading, the evaluation of PROs is performed without any

interpretation by a clinician, relative or anyone else and

reflects the patients’ subjective experience [1].

With the development of validated questionnaires with

robust psychometric properties over the last decades,

PROs have been established as valuable and reliable

complementary information in clinical studies [2].

Moreover, PRO assessment is recently regarded as quality

indicator in routine cancer care [3].

The reporting of PROs regarding symptoms and side effects

particularly in conjunction with the physician assessed

morbidity following standard grading systems has been

thoroughly investigated. A recently published literature

review analyzed 28 high quality studies and concluded

only fair to moderate associations between both

assessment methods; furthermore the majority of studies

demonstrated the tendency of underreporting morbidity

in the physician assessed grading systems [4].

Therefore, an initiative has been started in the United

States to combine both methods in a collaborative

approach to enable a comprehensive and in-depth

understanding of morbidity. The National Cancer Institute

(NCI) has recently published a patient questionnaire

version of the widely used Common Toxicity Criteria of

Adverse Events (CTCAE) [5,6]. The PRO-CTCAE enables

patients’ self-reporting of symptoms via paper

questionnaire, touchscreen tablet computer or interactive

voice response system [7]. To date, several translations

and linguistic validations of the PRO-CTCAE are in progress

and a widespread use in clinical cancer trials is expected

in the near future [8,9].

In Europe, the Patient Reported Outcomes and Behavioral

Evidence initiative (PROBE) within the European

Organisation for Research and Treatment of Cancer

(EORTC) [10] has recently reported on a meta-dataset

pooled from different international randomized controlled

clinical trials across different patient populations, disease

stages and treatments, which included the EORTC quality

of life assessment [11]. It has been shown that baseline

EORTC quality of life assessment increases the prognostic

accuracy for overall survival significantly (by 6-8%) on top

of clinical and sociodemographic risk factors. For each

cancer type, at least one specific quality of life domain

provided prognostic information, even though no universal

domain could be identified for all patients [12,13].

In conclusion, PROs add unique and highly valuable

information to clinical cancer trials and should be actively

promoted to complement physician assessed morbidity.