Morphological Adaptive Radiation Therapy: The impact of weekly anatomical changes

150 Pages·2017·6.56 MB·English

UUnniivveerrssiittyy ooff WWoolllloonnggoonngg
RReesseeaarrcchh OOnnlliinnee
University of Wollongong Thesis Collection
University of Wollongong Thesis Collections
2017+
2017
MMoorrpphhoollooggiiccaall AAddaappttiivvee RRaaddiiaattiioonn TThheerraappyy:: TThhee iimmppaacctt ooff wweeeekkllyy
aannaattoommiiccaall cchhaannggeess
Farhannah Aly
University of Wollongong
Follow this and additional works at: https://ro.uow.edu.au/theses1
UUnniivveerrssiittyy ooff WWoolllloonnggoonngg
CCooppyyrriigghhtt WWaarrnniinngg
You may print or download ONE copy of this document for the purpose of your own research or study. The University
does not authorise you to copy, communicate or otherwise make available electronically to any other person any
copyright material contained on this site.
You are reminded of the following: This work is copyright. Apart from any use permitted under the Copyright Act
1968, no part of this work may be reproduced by any process, nor may any other exclusive right be exercised,
without the permission of the author. Copyright owners are entitled to take legal action against persons who infringe
their copyright. A reproduction of material that is protected by copyright may be a copyright infringement. A court
may impose penalties and award damages in relation to offences and infringements relating to copyright material.
Higher penalties may apply, and higher damages may be awarded, for offences and infringements involving the
conversion of material into digital or electronic form.
UUnnlleessss ootthheerrwwiissee iinnddiiccaatteedd,, tthhee vviieewwss eexxpprreesssseedd iinn tthhiiss tthheessiiss aarree tthhoossee ooff tthhee aauutthhoorr aanndd ddoo nnoott nneecceessssaarriillyy
rreepprreesseenntt tthhee vviieewwss ooff tthhee UUnniivveerrssiittyy ooff WWoolllloonnggoonngg..
RReeccoommmmeennddeedd CCiittaattiioonn
Aly, Farhannah, Morphological Adaptive Radiation Therapy: The impact of weekly anatomical changes,
Master of Philosophy thesis, Centre for Medical Radiation Physics, University of Wollongong, 2017.
https://ro.uow.edu.au/theses1/267
Research Online is the open access institutional repository for the University of Wollongong. For further information
contact the UOW Library: [email protected]
Morphological Adaptive Radiation Therapy: The impact of
weekly anatomical changes.

Farhannah Aly
MBChB (Hons), FRANZCR

This thesis is presented as part of the requirements for the conferral of the degree:
Master of Philosophy

Supervisors:
Peter. E. Metcalfe, A. Andrew Miller

The University of Wollongong
Centre for Medical Radiation Physics
Faculty of Engineering and Information Sciences

December, 2017
This work Qc copyright by Farhannah Aly, 2017. All Rights Reserved.

No part of this work may be reproduced, stored in a retrieval system, transmitted, in any form or by
any means, electronic, mechanical, photocopying, recording, or otherwise, without the prior
permission of the author or the University of Wollongong.

This research has been conducted with the support of an Australian Government Research Training
Program Scholarship.
Declaration

I, Farhannah Aly, declare that this thesis is submitted in partial fulfilment of the
requirements for the conferral of the degree Master of Philosophy, from the
University of Wollongong, is wholly my own work unless otherwise referenced or
acknowledged. This document has not been submitted for qualifications at any other
academic institution.

Farhannah Aly

December 1, 2017
Table of contents

List of Tables v
List of Figures vii
Acknowledgements viii
Publications x
Conference presentations xi
Invited talks xii
List of Abbreviations xiii
Abstract xv
1 Introduction
1.1 Introduction 1
1.2 Project Aims 7
1.3 Chapter Overview 8
2 Literature Review
2.1 Changes in Patient Weight Occurring During Radiotherapy for Head and Neck
9
Cancer
2.2 Anatomical Changes in Tumour Volumes Occurring during Radiotherapy for
9
Head and Neck Cancer
2.3 Anatomical Changes in Organs At Risk Occurring during Radiotherapy for
11
Head and Neck Cancer
2.3.1 Parotid Gland 11
2.3.2 Submandibular Gland 13
2.3.3 Swallowing structures 14
2.3.4 The Neck 14
2.4 Dosimetric Changes to Tumour Volumes Occurring during Radiotherapy for
14
Head and Neck Cancer
2.5 Dosimetric Changes in Organs At Risk Occurring during Radiotherapy for
15
Head and Neck Cancer
2.5.1 Parotid Gland 15
2.5.2 Spinal Cord and Brainstem 17
2.5.3 Other OARs 18
2.6 Clinical Impact of Dosimetric Changes during Radiation Therapy 18
2.7 The Benefit of Adaptive Radiation Therapy in Head and Neck Cancer Patients 19
i
2.7.1 Impact of ART on Tumour Dose and Clinical Outcome 20
2.7.2 ART Impact on Organ At Risk Dose and Clinical Outcome 25
2.8 Implementation of ART for Head and Neck Cancer Patients 30
2.8.1 Clinical Resource Impact 30
2.8.2 Factors Which Correlate with Inadequate Dose Delivery 31

2.8.3 Recommendations for ART Implementation 40
2.9 A Tool for Assessment of Patient Nutritional Status 41
3 Methods
3.1 Study Design 43
3.2 Study Population 43
3.2.1 Patient Selection 43
3.2.2 Eligibility Criteria 43
3.2.3 Ineligibility Criteria 44
3.3 Pretreatment Evaluation 44
3.4 Radiation Treatment Planning and Plan Assessment 46
3.4.1 Radiation Treatment Schedule 46
3.4.2 Planning CT Procedure 46
3.4.3 Target Volume definitions 46
3.4.4 Dose Calculation 52

3.4.5 Treatment Prescription 52
3.4.6 Weekly Imaging and IMRT Plan Assessment 52
3.4.7 Weekly Patient Assessment 53
3.4.8 Statistical Analysis 54
3.4.9 Comparison of Methodology with Other Studies 54
4 General Results
4.1 Patient Cohort 56
4.2 Adaptive Replanning 56
4.2.1 Plan Adaptation Timing and Frequency 59
4.3 Weight and Nutritional Score 61
4.3.1 Weight Loss and the Need for New Bolus or Immobilisation Mask 61
4.3.2 Change in Nutritional Score 62
4.4 Correlation with Plan Adaptation Requirement 63
4.5 Overall Time for Target Delineation and Planning Process 64
ii
5 Anatomical Changes Observed during H+N IMRT
5.1 Volumetric Changes in Target Volumes 65
5.1.1 Full Patient Cohort 65
5.1.2 Patients with CT Scan at Fraction One 66
5.2 Volumetric Changes in Salivary Glands 69
5.2.1 Parotid Glands 69
5.2.2 Submandibular Glands 69
5.3 Positional Changes in Salivary Glands 72
5.3.1 Parotid Glands 72
5.3.2 Submandibular Glands 74
5.4 Volumetric Changes in Subcutaneous Fat 74
6 Dosimetric Changes Observed during H+N IMRT
6.1 Dosimetric Changes in Planning Target Volumes 78
6.1.1 Original IMRT Plan 78
6.1.2 IMRT Plan Adaptation 80
6.2 Dosimetric Changes in Parotid Glands 83
6.2.1 Original IMRT Plan 83
6.2.2 IMRT Plan Adaptation 83
6.3 Dosimetric Changes in Spinal Canal 86
6.3.1 Original IMRT Plan 86
6.3.2 IMRT Plan Adaptation 86
7 Summary of Research, Discussion and Conclusions
7.1 Restatement of Project Aims and Research Questions 88
7.2 Summary of Research 89
7.2.1 Volumetric Changes Observed in the Target Volumes during H+N IMRT 89
7.2.2 Volumetric and Geometric Changes Observed in the Salivary Glands
90
during H+N IMRT
7.2.3 Changes Observed in Subcutaneous Fat Volume during H+N IMRT 91
7.2.4 Dose Delivery to PTVs during Unadapted and Adapted H+N IMRT 91
7.2.5 Dose Delivery to Parotid Glands during Unadapted and Adapted H+N
92
IMRT
7.2.6 Dose Delivery to Spinal Canal during Unadapted and Adapted H+N IMRT 93
7.2.7 Correlations with Need for Plan Adaptation 93
iii
7.3 Discussion 94
7.3.1 Impact of this Protocol on Departmental Workflow and Resource
94
Allocation
7.3.2 Contouring Accuracy and Consistency 95
7.3.3 Shrinking Tumour Volumes 96
7.3.4 The Use of PTV or CTV for Assessment of Tumour Dose Delivery 100
7.3.5 Interpretation of Dosimetric Results 101
7.3.6 Frequency of Imaging and Adaptive Replanning 103
7.3.7 Timing of Adaptive Replanning 104
7.3.8 Strengths of this Investigation 104
7.3.9 Limitations of this Investigation 105
7.3.10 Recommendations as a Result of this Investigation 106
7.3.11 Future Research Directions 107
7.3.12 A Cone Beam CT Imaging Protocol 108
7.4 Conclusions 109
References 111
Appendix 1 Patient Generated Subjective Global Assessment (PG-SGA) Worksheet 122
Appendix 2 ECOG Performance Status Categories 125
Appendix 3 Concept Outline for Future Investigation 126

iv
List of Tables

2.1 Studies reporting on effect of plan adaptation on TV coverage and clinical tumour
23
outcomes
2.2 Studies reporting on effect of plan adaptation on OAR coverage and clinical outcomes 27
2.3 Studies reporting correlations with parotid gland dosimetry. 33
2.4 Studies reporting correlations with spinal cord and brainstem dosimetry. 36
2.5 Studies reporting correlations with dosimetry of other structures. 38
2.6 Studies reporting recommendations, in terms of selection criteria or optimal timing,
41
for implementing an ART protocol.
3.1 Schedule of clinical patient review and imaging 45
4.1 Main patient characteristics and adaptive planning schedule 57
4.2 Patient survival outcomes 58
4.3 Frequency of weekly plan adaptations 61
4.4 Mean PG-SGA score and PG-SGA category frequency for the patient cohort. 63
5.1 Mean volume (+ standard deviation) of target volumes during radiation treatment. 67
5.2 Volume changes in TVs of patients who underwent CT imaging at fraction 0. 68
5.3 Mean Parotid Gland (right and left) volume, with standard deviation, during the
70
treatment period.
5.4 Mean Submandibular Gland (right and left) volume, with standard deviation, during
71
the treatment period.
5.5 Parotid Gland movement, relative to position at planning CT scan, measured by
73
different calculation methods.
5.6 Submandibular Gland movement, relative to position at planning CT scan. 74
5.7 Mean volume (+ standard deviation) of fat during radiation treatment; measuring fat
76
volume in different numbers of CT scan slices.
5.8 Mean reduction in volume of fat during radiation treatment; measuring fat volume in
77
different numbers of CT scan slices.
6.1 Mean PTV coverage (+ standard deviation) of the Planning Target Volumes (PTV70
80
and PTV60) with original IMRT plan.
6.2 Mean PTV coverage (+ standard deviation) of original plan versus adaptive planning
81
strategy during radiation treatment.
6.3 Mean V26 (+ standard deviation) of parotid glands with original IMRT plan. 83

v
6.4 Mean V26 values of parotid glands for all replanning events; comparing the original
84
IMRT plan (Original) vs. adaptive replan (ART1) vs. retrospective replan (ART2).
6.5 Volume of spinal canal receiving >45 Gy and maximum dose to spinal canal (+
86
standard deviation) with original IMRT plan.
6.6 Volume of spinal canal receiving >45 Gy and maximum dose to spinal canal for all 22
replanning events; comparing the original IMRT plan (Original) vs. adaptive replan 87
(ART1).
7.1 Volume change in soft tissue comprising CTV volumes over the treatment course. 99

vi