Cochlea-sparing acoustic neuroma treatment with 4π radiation therapy.

PurposeThis study investigates whether 4π noncoplanar radiation therapy can spare the cochleae and consequently potentially improve hearing preservation in patients with acoustic neuroma who are treated with radiation therapy.Methods and materialsClinical radiation therapy plans for 30 patients with acoustic neuroma were included (14 stereotactic radiation surgery [SRS], 6 stereotactic radiation therapy [SRT], and 10 intensity modulated radiation therapy [IMRT]). The 4π plans were created for each patient with 20 optimal beams selected using a greedy column generation method and subsequently recalculated in Eclipse for comparison. Organ-at-risk (OAR) doses, homogeneity index, conformity, and tumor control probability (TCP) were compared. Normal tissue complication probability (NTCP) was calculated for sensorineural hearing loss (SNHL) at 3 and 5 years posttreatment. The dose for each plan was then escalated to achieve 99.5% TCP.Results4π significantly reduced the mean dose to both cochleae by 2.0 Gy (32%) for SRS, 3.2 Gy (29%) for SRT, and 10.0 Gy (32%) for IMRT. The maximum dose to both cochleae was also reduced with 4π by 1.6 Gy (20%), 2.2 Gy (15%), and 7.1 Gy (18%) for SRS, SRT, and IMRT plans, respectively. The reductions in mean/maximum brainstem dose with 4π were also statistically significant. Mean doses to other OARs were reduced by 19% to 56% on average. 4π plans had a similar CN and TCP, with a significantly higher average homogeneity index (0.93 vs 0.92) and significantly lower average NTCP for SNHL at both 3 years (30.8% vs 40.8%) and 5 years (43.3% vs 61.7%). An average dose escalation of approximately 116% of the prescription dose achieved 99.5% TCP, which resulted in 32.6% and 43.4% NTCP for SNHL at 3 years and 46.4% and 64.7% at 5 years for 4π and clinical plans, respectively.ConclusionsCompared with clinical planning methods, optimized 4π radiation therapy enables statistically significant sparing of the cochleae in acoustic neuroma treatment as well as lowering of other OAR doses, potentially reducing the risk of hearing loss

Automated Treatment Planning and Non-coplanar Beam Angles in Radiotherapy

Automation of the treatment plan generation in radiotherapy showed to play a key role in patient care. It can highly improve plan quality, reduce planner influence, increase standardization and easily generate a high numb

Can intensity-modulated radiotherapy (IMRT) be used to reduce toxicity and improve tumour control in patients with head and neck cancer?

Radiotherapy is commonly used in the treatment of head and neck cancer. For early stage tumours, conventional radiotherapy techniques have a high cure rate and low levels of long-term complications. Patients with more advanced cancers have much lower cure rates and high levels of treatment-related complications. Intensity modulated radiotherapy (IMRT) is a new form of focussed radiation therapy. It has been used to reduce the radiation dose to normal tissue structures and increase the dose delivered to tumour bearing tissues. This potentially allows reduced side effects and increased tumour control compared to conventional radiotherapy. The rationale of this thesis was to test whether these twin goals could be achieved in head and neck cancer patients. The first part of the thesis describes improvements in patient immobilisation, optimisation of techniques for neck irradiation, and evaluation of the technique in a busy radiotherapy department. It includes pre-clinical evaluation of IMRT for different tumour sites, the development of quality assurance programs and the conduct of a national randomised controlled trial of parotid-sparing IMRT. This trial concluded that IMRT significantly reduced patient-reported xerostomia, allowed recovery of saliva production and improved quality of life. The second part of the thesis describes pre-clinical evaluation of techniques to escalate radiation dose in patients with larynx and hypopharynx tumours. A phase I/II clinical trial showed that higher doses of radiation can be delivered at the expense of an increase in acute radiation toxicity but without a measurable increase in late radiation side effects. In the larynx and hypopharynx groups, a possible increase in local control was observed. This thesis describes the process of evaluation of a new radiotherapy technology and could be used as a template for testing other new technologies in the future.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Orale bivirkninger for pasienter som får strålebehandling i forbindelse med behandling av hode-/halskreft, rapportert i form av PROMS-spørreskjema

Bakgrunn: Oral mukositt (OM) er blant de vanligste orale bivirkningene som oppstår blant pasienter som gjennomgår stråleterapi mot hode-/halsområdet. Det er i dag behov for rapporteringsverktøy for subjektive symptomer, for å kunne tilrettelegge for den enkelte pasient gjennom kreftbehandlingen, samt å kunne måle effektiviteten av medisinske tiltak. Patient-Reported Oral Mucositis Symptom (PROMS)-spørreskjema er et rapporteringsverktøy som ble utprøvd og validert til bruk blant hode-/halskreftpasienter i et forskningsprosjekt i Canada. Behovet for et tilsvarende skjema på norsk, gjorde at dette kvalitetsevalueringsprosjektet ble satt i gang. Hensikt og problemstilling: Formålet med kvalitetsevalueringsprosjektet, var å sammenligne de rapporterte PROMS-scorene fra en gruppe hode-/halskreftpasienter som gjennomgikk strålebehandling i Toronto, Canada, med en tilsvarende pasientkohorte fra Tromsø, Norge. Videre var hensikten å evaluere om PROMS-spørreskjema kan benyttes blant hode-/halskreftpasienter i Norge, for å vurdere i hvilken grad OM påvirker hode-/halskreftpasientene underveis i strålebehandlingen. Materiale og metode: Pasienter på øre-nese-hals (ØNH)-avdelingen i Tromsø ble tilbudt å fylle ut en norsk versjon av PROMS-spørreskjema ukentlig, i de seks behandlingsukene de gjennomgikk strålebehandling mot hode-/halsregionen. Spørreskjemaene ble samlet inn av helsepersonell på avdelingen, og ble anonymisert før vi som masterstudenter fikk tilgang til materialet. PROMS-scorene ble målt til nærmeste millimeter på en visuell analog skala (VAS), og deretter systematisert i Excel. Resultatene ble framstilt i en graf, og sammenlignet med en tilsvarende graf fra Toronto. Resultater: Studien som ble utført i Tromsø viste til at pasientrapportert funksjonsforstyrrelse og smerter, økte i takt med behandlingsforløpet, i samsvar med observasjoner gjort tidligere i Toronto. Pasientene fra Toronto scoret høyere enn pasientene fra Tromsø, gjennom de siste behandlingsukene. Konklusjon: Dette kvalitetsevalueringsprosjektet konkluderer med at PROMS-spørreskjema oversatt til norsk, kan benyttes under pasientbehandling, enten som supplement, eller som erstatning for klinisk undersøkelse, i de tilfellene hvor dette er indisert

Towards patient selection for cranial proton beam therapy – Assessment of current patient-individual treatment decision strategies

Proton beam therapy shows dosimetric advantages in terms of sparing healthy tissue compared to conventional photon radiotherapy. Those patients who are supposed to experience the greatest reduction in side effects should preferably be treated with proton beam therapy. One option for this patient selection is the model-based approach. Its feasibility in patients with intracranial tumours is investigated in this thesis. First, normal tissue complication probability models for early and late side effects were developed and validated in external cohorts based on data of patients treated with proton beam therapy. Acute erythema as well as acute and late alopecia were associated with high-dose parameters of the skin. Late mild hearing loss was related to the mean dose of the ipsilateral cochlea. Second, neurocognitive function as a relevant side effect for brain tumour patients was investigated in detail using subjective and objective measures. It remained largely stable during recurrence-free follow-up until two years after proton beam therapy. Finally, potential toxicity differences were evaluated based on an individual proton and photon treatment plan comparison as well as on models predicting various side effects. Although proton beam therapy was able to achieve a high relative reduction of dose exposure in contralateral organs at risk, the associated reduction of side effect probabilities was less pronounced. Using a model-based selection procedure, the majority of the examined patients would have been eligible for proton beam therapy, mainly due to the predictions of a model on neurocognitive function.:1. Introduction 2. Theoretical background 2.1 Treatment strategies for tumours in the brain and skull base 2.1.1 Gliomas 2.1.2 Meningiomas 2.1.3 Pituitary adenomas 2.1.4 Tumours of the skull base 2.1.5 Role of proton beam therapy 2.2 Radiotherapy with photons and protons 2.2.1 Biological effect of radiation 2.2.2 Basic physical principles of radiotherapy 2.2.3 Field formation in radiotherapy 2.2.4 Target definition and delineation of organs at risk 2.2.5 Treatment plan assessment 2.3 Patient outcome 2.3.1 Scoring of side effects 2.3.2 Patient-reported outcome measures – Quality of life 2.3.3 Measures of neurocognitive function 2.4 Normal tissue complication probability models 2.4.1 Types of NTCP models 2.4.2 Endpoint definition and parameter fitting 2.4.3 Assessment of model performance 2.4.4 Model validation 2.5 Model-based approach for patient selection for proton beam therapy 2.5.1 Limits of randomised controlled trials 2.5.2 Principles of the model-based approach 3. Investigated patient cohorts 4. Modelling of side effects following cranial proton beam therapy 4.1 Experimental design for modelling early and late side effects 4.2 Modelling of early side effects 4.2.1 Results 4.2.2 Discussion 4.3 Modelling of late side effects 4.3.1 Results 4.3.2 Discussion 4.4 Interobserver variability of alopecia and erythema assessment 4.4.1 Patient cohort and experimental design 4.4.2 Results 4.4.3 Discussion 4.5 Summary 5. Assessing the neurocognitive function following cranial proton beam therapy 5.1 Patient cohort and experimental design 5.2 Results 5.2.1 Performance at baseline 5.2.2 Correlation between subjective and objective measures 5.2.3 Time-dependent score analyses 5.3 Discussion and conclusion 5.4 Summary 6. Treatment plan and NTCP comparison for patients with intracranial tumours 6.1 Motivation 6.2 Treatment plan comparison of cranial proton and photon radiotherapy 6.2.1 Patient cohort and experimental design 6.2.2 Results 6.2.3 Discussion 6.3 Application of NTCP models 6.3.1 Patient cohort and experimental design 6.3.2 Results 6.3.3 Discussion 6.4 Summary 7. Conclusion and further perspectives 8. Zusammenfassung 9. Summar