- Email: [email protected]
Brief Report on Radiological Changes following Stereotactic Ablative Radiotherapy (SABR) for Early-Stage Lung Tumors: A Pictorial Essay
Accepted Manuscript Brief report on radiological changes following stereotactic ablative radiotherapy (SABR) for early-stage lung tumors: a pictorial essay Merle I. Ronden, David Palma, Ben J. Slotman, Suresh Senan PII:
S1556-0864(18)30177-1
DOI:
10.1016/j.jtho.2018.02.023
Reference:
JTHO 889
To appear in:
Journal of Thoracic Oncology
Received Date: 26 November 2017 Revised Date:
12 February 2018
Accepted Date: 15 February 2018
Please cite this article as: Ronden MI, Palma D, Slotman BJ, Senan S, on behalf of the Advanced Radiation Technology Committee of the International Association for the Study of Lung Cancer, Brief report on radiological changes following stereotactic ablative radiotherapy (SABR) for early-stage lung tumors: a pictorial essay, Journal of Thoracic Oncology (2018), doi: 10.1016/j.jtho.2018.02.023. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT 1
Brief report on radiological changes following stereotactic ablative
2
radiotherapy (SABR) for early-stage lung tumors: a pictorial essay
3 Merle I. Ronden(1), David Palma(2), Ben J. Slotman(1), Suresh Senan(1), on behalf
5
of the Advanced Radiation Technology Committee of the International Association for
6
the Study of Lung Cancer
RI PT
4
7 8
1 Department of Radiation Oncology, VU University Medical Center, Amsterdam, The
9
Netherlands
2 Department of Radiation Oncology, London Health Sciences Centre, London,
11
Ontario, Canada
SC
10
12 Corresponding author:
14
Professor Suresh Senan FRCR, PhD
15
Department of Radiation Oncology, VU University Medical Center, 1081 HV
16
Amsterdam, The Netherlands
17
Postal address: Postbox 7057, 1007 MB Amsterdam, The Netherlands
18
Telephone number: 0031 20 444 0414
19
Email: [email protected]
TE D
EP
21
AC C
20
M AN U
13
1
ACCEPTED MANUSCRIPT Disclosure of funding and conflict of interest statement
23
B.J.S. has received grants and speakers honoraria from Varian Medical Systems,
24
ViewRay Inc. and
25
BrainLAB AG, disclosures which were outside the scope of this study. D.P. reports a
26
pending US patent.
27
S.S. reports personal fees from Eli Lilly and AstraZeneca, as well as department
28
research grants from
29
ViewRay Inc, outside the submitted work. M.I. has no disclosures.
RI PT
22
30
SC
31 Abstract
33
Distinctive patterns of early and late benign fibrosis are commonly observed after
34
stereotactic ablative radiotherapy (SABR) for lung malignancies. These changes on
35
computed tomographic scans need to be distinguished from so-called ‘high-risk’
36
radiological features, which can be associated with a higher risk for tumor
37
recurrence. This pictorial report illustrates the different radiological changes seen
38
following SABR delivered using the volumetric modulated radiotherapy, a technique
39
which is
40
increasingly used in clinical care.
TE D
EP AC C
41
M AN U
32
2
ACCEPTED MANUSCRIPT 42
Introduction
43 Stereotactic ablative radiotherapy (SABR) is now an established treatment for
45
patients with early stage lung cancer. Evolving radiological changes are common
46
after SABR, and the typical patterns seen can be subdivided into either acute or late
47
radiological changes. Acute changes present within the first 6 months after SABR,
48
and late radiological changes manifest at 6 months or later (1-2). Acute radiological
49
changes on CT scan are sub-classified into the following categories: diffuse
50
consolidation, patchy consolidation, diffuse ground glass opacity (diffuse GGO) and
51
patchy ground glass opacity (patchy GGO) (1). Late radiological changes are
52
categorized into “modified conventional” pattern of fibrosis, scar-like fibrosis and
53
mass-like fibrosis (1). The classification of patients into these groups are associated
54
with modest interobserver agreement, which appears to improve with training (3).
M AN U
SC
RI PT
44
55
Following SABR, radiological changes develop in most patients (1, 4), but the
57
frequency and timing of radiological changes can vary depending on the SABR
58
delivery technique used (1, 5). We previously described the typical radiological
59
changes developing in patients who had undergone SABR using an older fixed-beam
60
delivery approach (1). The most frequent acute radiological changes seen after fixed-
61
beam delivery are diffuse consolidation (in 24% of patients), and patchy consolidation
62
(in 21%) (11), followed by diffuse GGO (8%) and patchy GGO (8%). However, many
63
institutions currently use volumetric modulated radiotherapy (VMAT) for SABR
64
delivery as it allows for faster treatments (5). Late radiological changes are
65
commoner following VMAT, with the most frequent change being a modified-
66
conventional pattern (62%), a pattern characterized by consolidation, volume loss,
67
and bronchiectasis (5, 11). Occasionally, scar-like (15%) or mass-like lung fibrosis
68
(14%) are observed after SABR, with the latter being difficult to distinguish from a
69
local recurrence.
AC C
EP
TE D
56
70 71
Several ‘high-risk’ radiological features (HRF) have been identified that may allow for
72
the differentiation between fibrosis or tumor recurrence (6-10). A HRF classification
73
system was derived from a systematic literature review, and included features such
74
as an enlarging opacity, sequential enlarging opacity, craniocaudal growth, bulging
75
margin, loss of linear margins and loss of air bronchogram (9, 11). However, 50% or 3
ACCEPTED MANUSCRIPT more of patients who did not go on to develop a local recurrence develop some
77
HRF’s after SABR (4). Most patients with tumor recurrences develop craniocaudal
78
growth of the radiological masses (9). The incidence of enlarging opacities in patients
79
with, and without recurrence, are reported to range from 92% versus 33-65% (4, 9,
80
11). The corresponding incidence of sequentially enlarging opacities were 67%
81
versus 0-14%. Features rarely seen in patients who did not go on to develop a
82
recurrence were bulging margins (seen in 2-17% of patients), linear margin
83
disappearance (0-2%), loss of air bronchogram (4-5%) and craniocaudal growth (2-
84
17%) (4,11).
RI PT
76
SC
85
Recently, a Delphi consensus process by international opinion leaders in thoracic
87
radiation oncology and radiology, concluded that the findings suspicious of a local
88
recurrence on CT scan were the following: infiltration into adjacent structures, bulging
89
margins, sustained growth, mass-like growth, spherical growth, cranio-caudal growth
90
and a loss of air bronchograms (12). The Delphi consensus recommended use of
91
FDG-PET/CT scans only when there was suspicion for a local recurrence.
M AN U
86
92
With the increased use of SABR for both lung tumors and metastases, and as more
94
specialists become involved in the care of long-term survivors, a more widespread
95
knowledge of post-SABR radiological features are essential. We illustrate both acute
96
and late radiological changes following VMAT SABR, as well as HRF’s, in this brief
97
report. We selected images that highlighted each feature in isolation, so that
98
clinicians can correctly interpret these features.
99
Methods
EP
TE D
93
A prospective database of all patients treated with SABR at our institution was
101
accessed in order to identify patients treated with VMAT SABR for early stage lung
102
cancer. Post-SABR CT scans were accessed in our radiological archives in order to
103
identify representative acute and late radiological changes, and HRF’s. All images
104
and corresponding medical records of the selected cases were then reviewed by an
105
experienced radiation oncologist. In selected cases, images of planning CT scans
106
were superimposed with the dose color wash showing regions receiving 30 Gy or
107
more, in order to illustrate the dose-related changes.
AC C
100
108 109
4
ACCEPTED MANUSCRIPT 110
Results
111
Figure 1: diffuse consolidation. A consolidation measuring more than 5 cm in largest
112
dimension. The involved region contains more consolidation than aerated lung (1).
113 Figure 2: patchy consolidation. A consolidation measuring less than 5 cm in largest
115
dimension and/or the involved region contains less consolidation than aerated lung
116
(1).
RI PT
114
117
Figure 3: diffuse ground glass opacity. A ground glass opacity (GGO) is defined as a
119
hazy increased opacity through which normal parenchymal structures (bronchi and
120
vessels) can be visualized. Histopathological causes of GGO are: partial filling of
121
airspaces; alveolar wall (interstitial) thickening due to fluid, cells, or fibrosis; partial
122
collapse of alveoli; increased capillary blood volume; or a combination of these, the
123
common factor is partial replacement of lung air (13). A diffuse GGO is a GGO of
124
more than 5 cm, without consolidation. The involved region contains more GGO than
125
normal lung (1). In this figure, the diffuse GGO was seen at a more caudal aspect of
126
the radiation field.
M AN U
SC
118
127
Figure 4: patchy ground glass opacity. A patchy GGO is defined as a GGO less than
129
5 cm, and/or the involved region contains less GGO than normal lung (1).
TE D
128
130
Figure 5: modified conventional pattern of fibrosis. Consolidation, volume loss, and
132
bronchiectasis similar to, bus usually less extensive than, conventional radiaton
133
fibrosis. Larger than the original tumor size. Occasionally with associated GGO (1).
AC C
134
EP
131
135
Figure 6: scar-like fibrosis. Linear opacity in the region of the tumor associated with
136
volume loss (1).
137 138
Figure 7: mass-like fibrosis. Mass-like fibrosis is defined as a well-circumscribed
139
consolidation that is limited to the area of high-dose irradiation (1).
140 141
Figure 8: subpleural radiation fibrosis. VMAT plans typically attempt to reduce chest
142
wall doses, leading to opacities parallel to treated chest wall region (2).
143
5
ACCEPTED MANUSCRIPT 144
Figure 9: air bronchograms. Visible air-filled broncho (low attenuation), due to
145
opacification of surrounding alveoli (high-attenuation). The branching, linear
146
lucencies appear when normally aerated pulmonary parenchyma is replaced by non-
147
aerated tissue, either fluid or cellular material (13).
148 Figure 10: enlarging opacity – high-risk radiological feature. Enlarging lung
150
abnormality with an increased density in the irradiated area, due to either radiation-
151
induced lung injury or recurrence of the tumor.
RI PT
149
152
Figure 11: sequential enlargement – high-risk radiological feature. An opacity that
154
continues to enlarge on serial CT scans.
155
SC
153
Figure 12: craniocaudal growth – high-risk radiological feature. Craniocaudal
157
enlargement of an opacity, accoring to the RESIST criteria >5mm and >20%. After
158
SABR, most fibrosis is expected in the axial plane. CT changes in craniocaudal
159
direction is less likely to be related to radiation injury (9).
M AN U
156
160
Figure 13: bulging margin – high-risk radiological feature. A new or persistent
162
convexity arising in the irradiated lesion, where previously a straight or concave
163
margin was present (8).
164
TE D
161
Figure 14: loss of linear margins – high-risk radiological feature. A previously straight
166
margin to the fibrotic area is replaced by a convex surface (8).
EP
165
167
Figure 15: loss of air bronchogram – high-risk radiological feature. Previously air-
169
filled airways show new or increasing opafication. Loss of air bronchogram can signal
170
tumor recurrence, but is also observed in cases without local recurrence (6-8).
171
AC C
168
172
Conclusion
173
As the number of long-term survivors following SABR for early stage lung cancer
174
increases, and as timely surgical salvage of local disease failure can result in cures
175
(14), all clinicians involved in follow-up of these patients should be familiar with the
176
expected radiological features associated with SABR. Distinguishing benign changes
6
ACCEPTED MANUSCRIPT 177
on CT scans from possible recurrences will also avoid unnecessary patient anxiety,
178
and will minimize the risks of toxicity from unnecessary diagnostic procedures.
179 References
181
1. Dahele M, Palma D, Lagerwaard F, et al. Radiological Changes After Stereotactic
182
Radiotherapy for Stage I Lung Cancer. J Thorac Oncol. 2011 Jul; 6 (7):1221-8.
183
2. Choi YW, Munden RF, Erasmus JJ et al. Effects of radiation therapy on the lung:
184
radiologic appearances and differential diagnosis. Radiographics. 2004; 24(4):985-
185
97.
186
3. Faruqi S, Giuliani ME, Raziee H, et al. Interrater reliability of the categorization of
187
late radiographic changes after lung stereotactic body radiation therapy. Int J Rad
188
Oncol Biol Phys 2014;89:1076-83.
189
4. Ronden MI, van Sörnsen de Koste JR, Johnson C, et al. Incidence of high-risk
190
radiological features in patients without local recurrence following SABR for early
191
stage non-small cell lung cancer. Int J Radiat Oncol Biol Phys. 2018 Jan
192
1;100(1):115-121.
193
5. Senthi S, Dahele M, van de Ven PM, et al. Late radiologic changes after
194
stereotactic ablative radiotherapy for early stage lung cancer: a comparison of fixed-
195
beam versus arc delivery techniques. Radiother Oncol. 2013 Oct;109(1):77-81.
196
6. Bourgouin P, Cousineau G, Lemire P, et al. Differentiation of radiation-induced
197
fibrosis from recurrent pulmonary neoplasm by CT. Can Assoc Radiol J. 1987 Mar;
198
38(1):23-6 .
199
7. Libshitz HI, Sheppard DG. Filling in of radiation therapy-induced bronchiectatic
200
change: a reliable sign of locally recurrent lung cancer. Radiology. 1999; 210(1):25–
201
27.
202
8. Kato S, Nambu A, Onishi H, et al. Computed tomography appearances of local
203
recurrence after stereotactic body radiation therapy for stage I non-small-cell lung
204
carcinoma. Jpn J Radiol. 2010; 28:259–265.
205
9. Huang K, Senthi S, Palma DA, et al. High risk CT features for detection of local
206
recurrence after stereotactic ablative radiotherapy for lung cancer. Radiother Oncol.
207
2013 Oct; 109(1):51-7.
208
10. Halpenny D, Ridge C, Hayes S, et al. Computed Tomographic Features
209
Predictive of Local Recurrence in Patients with Early Stage Lung Cancer Treated
210
with Stereotactic Body Radiation Therapy. Clin Imaging. 2015; 39(2):254–258.
AC C
EP
TE D
M AN U
SC
RI PT
180
7
ACCEPTED MANUSCRIPT 11. Huang K, Dahele M, Senan S, et al. Radiographic changes after lung stereotactic
212
ablative radiotherapy (SABR) – can we distinguish recurrence from fibrosis? A
213
systematic review of the literature. Radiother Oncol. 2012; 102:335–42.
214
12. Nguyen TK, Senan S, Bradley JD, et al. Optimal imaging surveillance after
215
stereotactic ablative radiation therapy for early-stage non-small cell lung cancer:
216
Findings of an International Delphi Consensus Study. Pract Radiat Oncol. 2017 Dec
217
29. pii: S1879-8500(17)30319-3. [Epub ahead of print].
218
13. Hansell DM, Bankier AA, MacMahon H, et al. Fleischner Society: Glossary of
219
Terms for Thoracic Imaging. Radiology. 2008 Mar; 246(3):697-722.
220
14. Verstegen NE, Maat AP, Lagerwaard FJ, et al. Salvage surgery for local failures
221
after stereotactic ablative radiotherapy for early stage non-small cell lung cancer.
222
Radiat Oncol. 2016; 11: 131.
AC C
EP
TE D
M AN U
SC
RI PT
211
8
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
S1556-0864(18)30177-1
DOI:
10.1016/j.jtho.2018.02.023
Reference:
JTHO 889
To appear in:
Journal of Thoracic Oncology
Received Date: 26 November 2017 Revised Date:
12 February 2018
Accepted Date: 15 February 2018
Please cite this article as: Ronden MI, Palma D, Slotman BJ, Senan S, on behalf of the Advanced Radiation Technology Committee of the International Association for the Study of Lung Cancer, Brief report on radiological changes following stereotactic ablative radiotherapy (SABR) for early-stage lung tumors: a pictorial essay, Journal of Thoracic Oncology (2018), doi: 10.1016/j.jtho.2018.02.023. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT 1
Brief report on radiological changes following stereotactic ablative
2
radiotherapy (SABR) for early-stage lung tumors: a pictorial essay
3 Merle I. Ronden(1), David Palma(2), Ben J. Slotman(1), Suresh Senan(1), on behalf
5
of the Advanced Radiation Technology Committee of the International Association for
6
the Study of Lung Cancer
RI PT
4
7 8
1 Department of Radiation Oncology, VU University Medical Center, Amsterdam, The
9
Netherlands
2 Department of Radiation Oncology, London Health Sciences Centre, London,
11
Ontario, Canada
SC
10
12 Corresponding author:
14
Professor Suresh Senan FRCR, PhD
15
Department of Radiation Oncology, VU University Medical Center, 1081 HV
16
Amsterdam, The Netherlands
17
Postal address: Postbox 7057, 1007 MB Amsterdam, The Netherlands
18
Telephone number: 0031 20 444 0414
19
Email: [email protected]
TE D
EP
21
AC C
20
M AN U
13
1
ACCEPTED MANUSCRIPT Disclosure of funding and conflict of interest statement
23
B.J.S. has received grants and speakers honoraria from Varian Medical Systems,
24
ViewRay Inc. and
25
BrainLAB AG, disclosures which were outside the scope of this study. D.P. reports a
26
pending US patent.
27
S.S. reports personal fees from Eli Lilly and AstraZeneca, as well as department
28
research grants from
29
ViewRay Inc, outside the submitted work. M.I. has no disclosures.
RI PT
22
30
SC
31 Abstract
33
Distinctive patterns of early and late benign fibrosis are commonly observed after
34
stereotactic ablative radiotherapy (SABR) for lung malignancies. These changes on
35
computed tomographic scans need to be distinguished from so-called ‘high-risk’
36
radiological features, which can be associated with a higher risk for tumor
37
recurrence. This pictorial report illustrates the different radiological changes seen
38
following SABR delivered using the volumetric modulated radiotherapy, a technique
39
which is
40
increasingly used in clinical care.
TE D
EP AC C
41
M AN U
32
2
ACCEPTED MANUSCRIPT 42
Introduction
43 Stereotactic ablative radiotherapy (SABR) is now an established treatment for
45
patients with early stage lung cancer. Evolving radiological changes are common
46
after SABR, and the typical patterns seen can be subdivided into either acute or late
47
radiological changes. Acute changes present within the first 6 months after SABR,
48
and late radiological changes manifest at 6 months or later (1-2). Acute radiological
49
changes on CT scan are sub-classified into the following categories: diffuse
50
consolidation, patchy consolidation, diffuse ground glass opacity (diffuse GGO) and
51
patchy ground glass opacity (patchy GGO) (1). Late radiological changes are
52
categorized into “modified conventional” pattern of fibrosis, scar-like fibrosis and
53
mass-like fibrosis (1). The classification of patients into these groups are associated
54
with modest interobserver agreement, which appears to improve with training (3).
M AN U
SC
RI PT
44
55
Following SABR, radiological changes develop in most patients (1, 4), but the
57
frequency and timing of radiological changes can vary depending on the SABR
58
delivery technique used (1, 5). We previously described the typical radiological
59
changes developing in patients who had undergone SABR using an older fixed-beam
60
delivery approach (1). The most frequent acute radiological changes seen after fixed-
61
beam delivery are diffuse consolidation (in 24% of patients), and patchy consolidation
62
(in 21%) (11), followed by diffuse GGO (8%) and patchy GGO (8%). However, many
63
institutions currently use volumetric modulated radiotherapy (VMAT) for SABR
64
delivery as it allows for faster treatments (5). Late radiological changes are
65
commoner following VMAT, with the most frequent change being a modified-
66
conventional pattern (62%), a pattern characterized by consolidation, volume loss,
67
and bronchiectasis (5, 11). Occasionally, scar-like (15%) or mass-like lung fibrosis
68
(14%) are observed after SABR, with the latter being difficult to distinguish from a
69
local recurrence.
AC C
EP
TE D
56
70 71
Several ‘high-risk’ radiological features (HRF) have been identified that may allow for
72
the differentiation between fibrosis or tumor recurrence (6-10). A HRF classification
73
system was derived from a systematic literature review, and included features such
74
as an enlarging opacity, sequential enlarging opacity, craniocaudal growth, bulging
75
margin, loss of linear margins and loss of air bronchogram (9, 11). However, 50% or 3
ACCEPTED MANUSCRIPT more of patients who did not go on to develop a local recurrence develop some
77
HRF’s after SABR (4). Most patients with tumor recurrences develop craniocaudal
78
growth of the radiological masses (9). The incidence of enlarging opacities in patients
79
with, and without recurrence, are reported to range from 92% versus 33-65% (4, 9,
80
11). The corresponding incidence of sequentially enlarging opacities were 67%
81
versus 0-14%. Features rarely seen in patients who did not go on to develop a
82
recurrence were bulging margins (seen in 2-17% of patients), linear margin
83
disappearance (0-2%), loss of air bronchogram (4-5%) and craniocaudal growth (2-
84
17%) (4,11).
RI PT
76
SC
85
Recently, a Delphi consensus process by international opinion leaders in thoracic
87
radiation oncology and radiology, concluded that the findings suspicious of a local
88
recurrence on CT scan were the following: infiltration into adjacent structures, bulging
89
margins, sustained growth, mass-like growth, spherical growth, cranio-caudal growth
90
and a loss of air bronchograms (12). The Delphi consensus recommended use of
91
FDG-PET/CT scans only when there was suspicion for a local recurrence.
M AN U
86
92
With the increased use of SABR for both lung tumors and metastases, and as more
94
specialists become involved in the care of long-term survivors, a more widespread
95
knowledge of post-SABR radiological features are essential. We illustrate both acute
96
and late radiological changes following VMAT SABR, as well as HRF’s, in this brief
97
report. We selected images that highlighted each feature in isolation, so that
98
clinicians can correctly interpret these features.
99
Methods
EP
TE D
93
A prospective database of all patients treated with SABR at our institution was
101
accessed in order to identify patients treated with VMAT SABR for early stage lung
102
cancer. Post-SABR CT scans were accessed in our radiological archives in order to
103
identify representative acute and late radiological changes, and HRF’s. All images
104
and corresponding medical records of the selected cases were then reviewed by an
105
experienced radiation oncologist. In selected cases, images of planning CT scans
106
were superimposed with the dose color wash showing regions receiving 30 Gy or
107
more, in order to illustrate the dose-related changes.
AC C
100
108 109
4
ACCEPTED MANUSCRIPT 110
Results
111
Figure 1: diffuse consolidation. A consolidation measuring more than 5 cm in largest
112
dimension. The involved region contains more consolidation than aerated lung (1).
113 Figure 2: patchy consolidation. A consolidation measuring less than 5 cm in largest
115
dimension and/or the involved region contains less consolidation than aerated lung
116
(1).
RI PT
114
117
Figure 3: diffuse ground glass opacity. A ground glass opacity (GGO) is defined as a
119
hazy increased opacity through which normal parenchymal structures (bronchi and
120
vessels) can be visualized. Histopathological causes of GGO are: partial filling of
121
airspaces; alveolar wall (interstitial) thickening due to fluid, cells, or fibrosis; partial
122
collapse of alveoli; increased capillary blood volume; or a combination of these, the
123
common factor is partial replacement of lung air (13). A diffuse GGO is a GGO of
124
more than 5 cm, without consolidation. The involved region contains more GGO than
125
normal lung (1). In this figure, the diffuse GGO was seen at a more caudal aspect of
126
the radiation field.
M AN U
SC
118
127
Figure 4: patchy ground glass opacity. A patchy GGO is defined as a GGO less than
129
5 cm, and/or the involved region contains less GGO than normal lung (1).
TE D
128
130
Figure 5: modified conventional pattern of fibrosis. Consolidation, volume loss, and
132
bronchiectasis similar to, bus usually less extensive than, conventional radiaton
133
fibrosis. Larger than the original tumor size. Occasionally with associated GGO (1).
AC C
134
EP
131
135
Figure 6: scar-like fibrosis. Linear opacity in the region of the tumor associated with
136
volume loss (1).
137 138
Figure 7: mass-like fibrosis. Mass-like fibrosis is defined as a well-circumscribed
139
consolidation that is limited to the area of high-dose irradiation (1).
140 141
Figure 8: subpleural radiation fibrosis. VMAT plans typically attempt to reduce chest
142
wall doses, leading to opacities parallel to treated chest wall region (2).
143
5
ACCEPTED MANUSCRIPT 144
Figure 9: air bronchograms. Visible air-filled broncho (low attenuation), due to
145
opacification of surrounding alveoli (high-attenuation). The branching, linear
146
lucencies appear when normally aerated pulmonary parenchyma is replaced by non-
147
aerated tissue, either fluid or cellular material (13).
148 Figure 10: enlarging opacity – high-risk radiological feature. Enlarging lung
150
abnormality with an increased density in the irradiated area, due to either radiation-
151
induced lung injury or recurrence of the tumor.
RI PT
149
152
Figure 11: sequential enlargement – high-risk radiological feature. An opacity that
154
continues to enlarge on serial CT scans.
155
SC
153
Figure 12: craniocaudal growth – high-risk radiological feature. Craniocaudal
157
enlargement of an opacity, accoring to the RESIST criteria >5mm and >20%. After
158
SABR, most fibrosis is expected in the axial plane. CT changes in craniocaudal
159
direction is less likely to be related to radiation injury (9).
M AN U
156
160
Figure 13: bulging margin – high-risk radiological feature. A new or persistent
162
convexity arising in the irradiated lesion, where previously a straight or concave
163
margin was present (8).
164
TE D
161
Figure 14: loss of linear margins – high-risk radiological feature. A previously straight
166
margin to the fibrotic area is replaced by a convex surface (8).
EP
165
167
Figure 15: loss of air bronchogram – high-risk radiological feature. Previously air-
169
filled airways show new or increasing opafication. Loss of air bronchogram can signal
170
tumor recurrence, but is also observed in cases without local recurrence (6-8).
171
AC C
168
172
Conclusion
173
As the number of long-term survivors following SABR for early stage lung cancer
174
increases, and as timely surgical salvage of local disease failure can result in cures
175
(14), all clinicians involved in follow-up of these patients should be familiar with the
176
expected radiological features associated with SABR. Distinguishing benign changes
6
ACCEPTED MANUSCRIPT 177
on CT scans from possible recurrences will also avoid unnecessary patient anxiety,
178
and will minimize the risks of toxicity from unnecessary diagnostic procedures.
179 References
181
1. Dahele M, Palma D, Lagerwaard F, et al. Radiological Changes After Stereotactic
182
Radiotherapy for Stage I Lung Cancer. J Thorac Oncol. 2011 Jul; 6 (7):1221-8.
183
2. Choi YW, Munden RF, Erasmus JJ et al. Effects of radiation therapy on the lung:
184
radiologic appearances and differential diagnosis. Radiographics. 2004; 24(4):985-
185
97.
186
3. Faruqi S, Giuliani ME, Raziee H, et al. Interrater reliability of the categorization of
187
late radiographic changes after lung stereotactic body radiation therapy. Int J Rad
188
Oncol Biol Phys 2014;89:1076-83.
189
4. Ronden MI, van Sörnsen de Koste JR, Johnson C, et al. Incidence of high-risk
190
radiological features in patients without local recurrence following SABR for early
191
stage non-small cell lung cancer. Int J Radiat Oncol Biol Phys. 2018 Jan
192
1;100(1):115-121.
193
5. Senthi S, Dahele M, van de Ven PM, et al. Late radiologic changes after
194
stereotactic ablative radiotherapy for early stage lung cancer: a comparison of fixed-
195
beam versus arc delivery techniques. Radiother Oncol. 2013 Oct;109(1):77-81.
196
6. Bourgouin P, Cousineau G, Lemire P, et al. Differentiation of radiation-induced
197
fibrosis from recurrent pulmonary neoplasm by CT. Can Assoc Radiol J. 1987 Mar;
198
38(1):23-6 .
199
7. Libshitz HI, Sheppard DG. Filling in of radiation therapy-induced bronchiectatic
200
change: a reliable sign of locally recurrent lung cancer. Radiology. 1999; 210(1):25–
201
27.
202
8. Kato S, Nambu A, Onishi H, et al. Computed tomography appearances of local
203
recurrence after stereotactic body radiation therapy for stage I non-small-cell lung
204
carcinoma. Jpn J Radiol. 2010; 28:259–265.
205
9. Huang K, Senthi S, Palma DA, et al. High risk CT features for detection of local
206
recurrence after stereotactic ablative radiotherapy for lung cancer. Radiother Oncol.
207
2013 Oct; 109(1):51-7.
208
10. Halpenny D, Ridge C, Hayes S, et al. Computed Tomographic Features
209
Predictive of Local Recurrence in Patients with Early Stage Lung Cancer Treated
210
with Stereotactic Body Radiation Therapy. Clin Imaging. 2015; 39(2):254–258.
AC C
EP
TE D
M AN U
SC
RI PT
180
7
ACCEPTED MANUSCRIPT 11. Huang K, Dahele M, Senan S, et al. Radiographic changes after lung stereotactic
212
ablative radiotherapy (SABR) – can we distinguish recurrence from fibrosis? A
213
systematic review of the literature. Radiother Oncol. 2012; 102:335–42.
214
12. Nguyen TK, Senan S, Bradley JD, et al. Optimal imaging surveillance after
215
stereotactic ablative radiation therapy for early-stage non-small cell lung cancer:
216
Findings of an International Delphi Consensus Study. Pract Radiat Oncol. 2017 Dec
217
29. pii: S1879-8500(17)30319-3. [Epub ahead of print].
218
13. Hansell DM, Bankier AA, MacMahon H, et al. Fleischner Society: Glossary of
219
Terms for Thoracic Imaging. Radiology. 2008 Mar; 246(3):697-722.
220
14. Verstegen NE, Maat AP, Lagerwaard FJ, et al. Salvage surgery for local failures
221
after stereotactic ablative radiotherapy for early stage non-small cell lung cancer.
222
Radiat Oncol. 2016; 11: 131.
AC C
EP
TE D
M AN U
SC
RI PT
211
8
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT