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Brief Report on Radiological Changes following Stereotactic Ablative Radiotherapy (SABR) for Early-Stage Lung Tumors: A Pictorial Essay

Open ArchivePublished:March 05, 2018DOI:https://doi.org/10.1016/j.jtho.2018.02.023

      Abstract

      Distinctive patterns of early and late benign fibrosis are commonly observed after stereotactic ablative radiotherapy for lung malignancies. These changes on computed tomography scans need to be distinguished from so-called high-risk radiological features, which can be associated with a higher risk for tumor recurrence. This pictorial report illustrates the different radiological changes seen after stereotactic ablative radiotherapy delivered by using volumetric modulated radiotherapy, a technique that is being increasingly used in clinical care.

      Keywords

      Introduction

      Stereotactic ablative radiotherapy (SABR) is now an established treatment for patients with early-stage lung cancer. Evolving radiological changes are common after SABR, and the typical patterns seen can be subdivided into either acute or late radiological changes. Acute changes present within the first 6 months after SABR, and late radiological changes manifest at 6 months or later.
      • Dahele M.
      • Palma D.
      • Lagerwaard F.
      • Slotman B.
      • Senan S.
      Radiological changes after stereotactic radiotherapy for stage I lung cancer.
      • Choi Y.W.
      • Munden R.F.
      • Erasmus J.J.
      • et al.
      Effects of radiation therapy on the lung: radiologic appearances and differential diagnosis.
      Acute radiological changes on computed tomography (CT) scan are subclassified into the following categories: diffuse consolidation, patchy consolidation, diffuse ground glass opacity (GGO), and patchy GGO.
      • Dahele M.
      • Palma D.
      • Lagerwaard F.
      • Slotman B.
      • Senan S.
      Radiological changes after stereotactic radiotherapy for stage I lung cancer.
      Late radiological changes are categorized into a modified conventional pattern of fibrosis, scar-like fibrosis, and mass-like fibrosis.
      • Dahele M.
      • Palma D.
      • Lagerwaard F.
      • Slotman B.
      • Senan S.
      Radiological changes after stereotactic radiotherapy for stage I lung cancer.
      The classification of patients into these groups is associated with modest interobserver agreement that appears to improve with training.
      • Faruqi S.
      • Giuliani M.E.
      • Raziee H.
      • et al.
      Interrater reliability of the categorization of late radiographic changes after lung stereotactic body radiation therapy.
      After SABR, radiological changes develop in most patients,
      • Dahele M.
      • Palma D.
      • Lagerwaard F.
      • Slotman B.
      • Senan S.
      Radiological changes after stereotactic radiotherapy for stage I lung cancer.
      • Ronden M.I.
      • van Sörnsen de Koste J.R.
      • Johnson C.
      • et al.
      Incidence of high-risk radiological features in patients without local recurrence following SABR for early-stage non-small cell lung cancer.
      but the frequency and timing of the radiological changes can vary depending on the SABR delivery technique used.
      • Dahele M.
      • Palma D.
      • Lagerwaard F.
      • Slotman B.
      • Senan S.
      Radiological changes after stereotactic radiotherapy for stage I lung cancer.
      • Senthi S.
      • Dahele M.
      • van de Ven P.M.
      • Slotman B.J.
      • Senan S.
      Late radiologic changes after stereotactic ablative radiotherapy for early stage lung cancer: a comparison of fixed-beam versus arc delivery techniques.
      We previously described the typical radiological changes developing in patients who had undergone SABR with an older fixed beam delivery approach.
      • Dahele M.
      • Palma D.
      • Lagerwaard F.
      • Slotman B.
      • Senan S.
      Radiological changes after stereotactic radiotherapy for stage I lung cancer.
      The most frequent acute radiological changes seen after fixed beam delivery are diffuse consolidation (in 24% of patients) and patchy consolidation (in 21%), followed by diffuse GGO (8%) and patchy GGO (8%).
      • Dahele M.
      • Palma D.
      • Lagerwaard F.
      • Slotman B.
      • Senan S.
      Radiological changes after stereotactic radiotherapy for stage I lung cancer.
      However, many institutions currently use volumetric modulated radiotherapy (VMAT) for SABR delivery, as it allows for faster treatments.
      • Senthi S.
      • Dahele M.
      • van de Ven P.M.
      • Slotman B.J.
      • Senan S.
      Late radiologic changes after stereotactic ablative radiotherapy for early stage lung cancer: a comparison of fixed-beam versus arc delivery techniques.
      Late radiological changes are more common after VMAT, with the most frequent change being a modified conventional pattern (62%), which is a pattern characterized by consolidation, volume loss, and bronchiectasis.
      • Senthi S.
      • Dahele M.
      • van de Ven P.M.
      • Slotman B.J.
      • Senan S.
      Late radiologic changes after stereotactic ablative radiotherapy for early stage lung cancer: a comparison of fixed-beam versus arc delivery techniques.
      • Bourgouin P.
      • Cousineau G.
      • Lemire P.
      • Delvecchio P.
      • Hébert G.
      Differentiation of radiation-induced fibrosis from recurrent pulmonary neoplasm by CT.
      Occasionally, scar-like (15%) or mass-like lung fibrosis (14%) is observed after SABR, with the latter being difficult to distinguish from a local recurrence.
      Several high-risk radiological features (HRFs) that may allow for the differentiation between fibrosis or tumor recurrence have been identified.
      • Libshitz H.I.
      • Sheppard D.G.
      Filling in of radiation therapy-induced bronchiectatic change: a reliable sign of locally recurrent lung cancer.
      • Kato S.
      • Nambu A.
      • Onishi H.
      • et al.
      Computed tomography appearances of local recurrence after stereotactic body radiation therapy for stage I non-small-cell lung carcinoma.
      • Huang K.
      • Senthi S.
      • Palma D.A.
      • et al.
      High risk CT features for detection of local recurrence after stereotactic ablative radiotherapy for lung cancer.
      • Halpenny D.
      • Ridge C.
      • Hayes S.
      • et al.
      Computed tomographic features predictive of local recurrence in patients with early stage lung cancer treated with stereotactic body radiation therapy.
      • Huang K.
      • Dahele M.
      • Senan S.
      • et al.
      Radiographic changes after lung stereotactic ablative radiotherapy (SABR) – can we distinguish recurrence from fibrosis? A systematic review of the literature.
      An HRF classification system was derived from a systematic literature review, and it included features such as an enlarging opacity, sequential enlarging opacity, craniocaudal growth, bulging margin, loss of linear margins, and loss of air bronchogram.
      • Huang K.
      • Senthi S.
      • Palma D.A.
      • et al.
      High risk CT features for detection of local recurrence after stereotactic ablative radiotherapy for lung cancer.
      • Huang K.
      • Dahele M.
      • Senan S.
      • et al.
      Radiographic changes after lung stereotactic ablative radiotherapy (SABR) – can we distinguish recurrence from fibrosis? A systematic review of the literature.
      However, in 50% or more of patients who did not subsequently experience local recurrence, some HRFs did develop after SABR.
      • Ronden M.I.
      • van Sörnsen de Koste J.R.
      • Johnson C.
      • et al.
      Incidence of high-risk radiological features in patients without local recurrence following SABR for early-stage non-small cell lung cancer.
      Craniocaudal growth of the radiological masses develops in most patients with tumor recurrence.
      • Huang K.
      • Senthi S.
      • Palma D.A.
      • et al.
      High risk CT features for detection of local recurrence after stereotactic ablative radiotherapy for lung cancer.
      The incidence of enlarging opacities in patients with and without recurrence are reported to range from 92% to between 33% and 65%.
      • Ronden M.I.
      • van Sörnsen de Koste J.R.
      • Johnson C.
      • et al.
      Incidence of high-risk radiological features in patients without local recurrence following SABR for early-stage non-small cell lung cancer.
      • Huang K.
      • Senthi S.
      • Palma D.A.
      • et al.
      High risk CT features for detection of local recurrence after stereotactic ablative radiotherapy for lung cancer.
      • Huang K.
      • Dahele M.
      • Senan S.
      • et al.
      Radiographic changes after lung stereotactic ablative radiotherapy (SABR) – can we distinguish recurrence from fibrosis? A systematic review of the literature.
      The corresponding incidences of sequentially enlarging opacities were 67% and 0% to 14%. Features rarely seen in patients without subsequent recurrence were bulging margins (seen in 2%–17% of patients), linear margin disappearance (0%–2%), loss of air bronchogram (4%–5%), and craniocaudal growth (2%–17%).
      • Ronden M.I.
      • van Sörnsen de Koste J.R.
      • Johnson C.
      • et al.
      Incidence of high-risk radiological features in patients without local recurrence following SABR for early-stage non-small cell lung cancer.
      • Huang K.
      • Dahele M.
      • Senan S.
      • et al.
      Radiographic changes after lung stereotactic ablative radiotherapy (SABR) – can we distinguish recurrence from fibrosis? A systematic review of the literature.
      Recently, a Delphi consensus process by international opinion leaders in thoracic radiation oncology and radiology concluded that the findings suggestive of a local recurrence on CT scan were as follows: infiltration into adjacent structures, bulging margins, sustained growth, mass-like growth, spherical growth, craniocaudal growth, and loss of air bronchograms.
      • Nguyen T.K.
      • Senan S.
      • Bradley J.D.
      • et al.
      Optimal imaging surveillance after stereotactic ablative radiation therapy for early-stage non-small cell lung cancer: findings of an International Delphi Consensus Study.
      The Delphi consensus recommended use of FDG-PET/CT scans only when local recurrence was suspected.
      With the increased use of SABR for both lung tumors and metastases, and as more specialists become involved in the care of long-term survivors, a more widespread knowledge of post-SABR radiological features is essential. We illustrate both acute and late radiological changes after VMAT SABR, as well as HRFs, in this brief report. We have selected images that highlight each feature in isolation so that clinicians can correctly interpret these features.

      Methods

      A prospective database of all patients treated with SABR at our institution was accessed to identify patients treated with VMAT SABR for early-stage lung cancer. Post-SABR CT scans were accessed in our radiological archives to identify representative acute and late radiological changes, and HRFs. All images and corresponding medical records of the selected cases were then reviewed by an experienced radiation oncologist. In selected cases, images of planning CT scans were superimposed with the dose color wash showing regions receiving 30 Gy or more to illustrate the dose-related changes.

      Results

      Typical radiological findings following SABR, as well as HRF's, are illustrated in Figure 1, Figure 2, Figure 3, Figure 4, Figure 5, Figure 6, Figure 7, Figure 8, Figure 9, Figure 10, Figure 11, Figure 12, Figure 13, Figure 14, Figure 15.
      Figure thumbnail gr1
      Figure 1Diffuse consolidation. A consolidation measuring more than 5 cm in the largest dimension. The involved region contains more consolidation than aerated lung.
      • Dahele M.
      • Palma D.
      • Lagerwaard F.
      • Slotman B.
      • Senan S.
      Radiological changes after stereotactic radiotherapy for stage I lung cancer.
      SABR, stereotactic ablative radiotherapy; CT computed tomography.
      Figure thumbnail gr2
      Figure 2Patchy consolidation. A consolidation measuring less than 5 cm in the largest dimension and/or when the involved region contains less consolidation than aerated lung.
      • Dahele M.
      • Palma D.
      • Lagerwaard F.
      • Slotman B.
      • Senan S.
      Radiological changes after stereotactic radiotherapy for stage I lung cancer.
      SABR, stereotactic ablative radiotherapy; CT computed tomography.
      Figure thumbnail gr3
      Figure 3Diffuse ground glass opacity (GGO). A GGO is defined as a hazy increased opacity through which normal parenchymal structures (bronchi and vessels) can be visualized. Histopathological causes of GGO are partial filling of airspaces; alveolar wall (interstitial) thickening due to fluid, cells, or fibrosis; partial collapse of alveoli; increased capillary blood volume; or a combination of these, with the common factor being partial replacement of lung air.
      • Hansell D.M.
      • Bankier A.A.
      • MacMahon H.
      • McLoud T.C.
      • Müller N.L.
      • Remy J.
      Fleischner Society: Glossary of Terms for Thoracic Imaging.
      A diffuse GGO is a GGO of more than 5 cm without consolidation. The involved region contains more GGO than normal lung.
      • Dahele M.
      • Palma D.
      • Lagerwaard F.
      • Slotman B.
      • Senan S.
      Radiological changes after stereotactic radiotherapy for stage I lung cancer.
      In this figure, the diffuse GGO was seen at a more caudal aspect of the radiation field. SABR, stereotactic ablative radiotherapy; CT computed tomography.
      Figure thumbnail gr4
      Figure 4Patchy ground glass opacity. A patchy ground glass opacity (GGO) is defined as a GGO less than 5 cm and/or when the involved region contains less GGO than normal lung.
      • Dahele M.
      • Palma D.
      • Lagerwaard F.
      • Slotman B.
      • Senan S.
      Radiological changes after stereotactic radiotherapy for stage I lung cancer.
      SABR, stereotactic ablative radiotherapy; CT computed tomography.
      Figure thumbnail gr5
      Figure 5Modified conventional pattern of fibrosis. Consolidation, volume loss, and bronchiectasis similar to but usually less extensive than conventional radiation fibrosis. Larger than the original tumor size, and occasionally with associated GGO.
      • Dahele M.
      • Palma D.
      • Lagerwaard F.
      • Slotman B.
      • Senan S.
      Radiological changes after stereotactic radiotherapy for stage I lung cancer.
      SABR, stereotactic ablative radiotherapy; CT computed tomography.
      Figure thumbnail gr6
      Figure 6Scar-like fibrosis. Linear opacity in the region of the tumor associated with volume loss.
      • Dahele M.
      • Palma D.
      • Lagerwaard F.
      • Slotman B.
      • Senan S.
      Radiological changes after stereotactic radiotherapy for stage I lung cancer.
      SABR, stereotactic ablative radiotherapy; CT computed tomography.
      Figure thumbnail gr7
      Figure 7Mass-like fibrosis. Mass-like fibrosis is defined as a well-circumscribed consolidation that is limited to the area of high-dose irradiation.
      • Dahele M.
      • Palma D.
      • Lagerwaard F.
      • Slotman B.
      • Senan S.
      Radiological changes after stereotactic radiotherapy for stage I lung cancer.
      SABR, stereotactic ablative radiotherapy; CT computed tomography.
      Figure thumbnail gr8
      Figure 8Subpleural radiation fibrosis. Volumetric modulated radiotherapy plans typically attempt to reduce chest wall doses, leading to opacities parallel to the treated chest wall region.
      • Choi Y.W.
      • Munden R.F.
      • Erasmus J.J.
      • et al.
      Effects of radiation therapy on the lung: radiologic appearances and differential diagnosis.
      SABR, stereotactic ablative radiotherapy; CT computed tomography.
      Figure thumbnail gr9
      Figure 9Air bronchograms. Visible air-filled bronchi (low attenuation) due to opacification of surrounding alveoli (high attenuation). The branching, linear lucencies appear when normally aerated pulmonary parenchyma is replaced by nonaerated tissue, either fluid or cellular material.
      • Hansell D.M.
      • Bankier A.A.
      • MacMahon H.
      • McLoud T.C.
      • Müller N.L.
      • Remy J.
      Fleischner Society: Glossary of Terms for Thoracic Imaging.
      SABR, stereotactic ablative radiotherapy; CT computed tomography.
      Figure thumbnail gr10
      Figure 10Enlarging opacity—a high-risk radiological feature. Enlarging lung abnormality with an increased density in the irradiated area that is due to either radiation-induced lung injury or recurrence of the tumor. SABR, stereotactic ablative radiotherapy; CT computed tomography.
      Figure thumbnail gr11
      Figure 11Sequential enlargement—a high-risk radiological feature. An opacity that continues to enlarge on serial computed tomography (CT) scans. SABR, stereotactic ablative radiotherapy.
      Figure thumbnail gr12
      Figure 12Craniocaudal growth—a high-risk radiological feature. Craniocaudal enlargement of an opacity (according to the Response Evaluation Criteria in Solid Tumors criteria, ≥5 mm and ≥20%). After SABR, most fibrosis is expected in the axial plane. Computed tomography (CT) changes in a craniocaudal direction is less likely to be related to radiation injury.
      • Halpenny D.
      • Ridge C.
      • Hayes S.
      • et al.
      Computed tomographic features predictive of local recurrence in patients with early stage lung cancer treated with stereotactic body radiation therapy.
      SABR, stereotactic ablative radiotherapy.
      Figure thumbnail gr13
      Figure 13Bulging margin—a high-risk radiological feature. A new or persistent convexity arising in the irradiated lesion, where previously a straight or concave margin was present.
      • Huang K.
      • Senthi S.
      • Palma D.A.
      • et al.
      High risk CT features for detection of local recurrence after stereotactic ablative radiotherapy for lung cancer.
      SABR, stereotactic ablative radiotherapy; CT computed tomography.
      Figure thumbnail gr14
      Figure 14Loss of linear margins—a high-risk radiological feature. A previously straight margin to the fibrotic area is replaced by a convex surface.
      • Huang K.
      • Senthi S.
      • Palma D.A.
      • et al.
      High risk CT features for detection of local recurrence after stereotactic ablative radiotherapy for lung cancer.
      SABR, stereotactic ablative radiotherapy; CT computed tomography.
      Figure thumbnail gr15
      Figure 15Loss of air bronchogram—a high-risk radiological feature. Previously air-filled airways show new or increasing opacification. Loss of air bronchogram can signal tumor recurrence but is also observed in cases without local recurrence.
      • Libshitz H.I.
      • Sheppard D.G.
      Filling in of radiation therapy-induced bronchiectatic change: a reliable sign of locally recurrent lung cancer.
      • Kato S.
      • Nambu A.
      • Onishi H.
      • et al.
      Computed tomography appearances of local recurrence after stereotactic body radiation therapy for stage I non-small-cell lung carcinoma.
      • Huang K.
      • Senthi S.
      • Palma D.A.
      • et al.
      High risk CT features for detection of local recurrence after stereotactic ablative radiotherapy for lung cancer.
      SABR, stereotactic ablative radiotherapy; CT computed tomography.

      Conclusion

      As the number of long-term survivors after SABR for early-stage lung cancer increases, and as timely surgical salvage of local disease failure can result in cures,
      • Verstegen N.E.
      • Maat A.P.
      • Lagerwaard F.J.
      • et al.
      Salvage surgery for local failures after stereotactic ablative radiotherapy for early stage non-small cell lung cancer.
      all clinicians involved in follow-up of these patients should be familiar with the expected radiological features associated with SABR. Distinguishing benign changes on CT scans from possible recurrences will also avoid unnecessary patient anxiety and minimize the risks of toxicity from unnecessary diagnostic procedures.

      References

        • Dahele M.
        • Palma D.
        • Lagerwaard F.
        • Slotman B.
        • Senan S.
        Radiological changes after stereotactic radiotherapy for stage I lung cancer.
        J Thorac Oncol. 2011; 6: 1221-1228
        • Choi Y.W.
        • Munden R.F.
        • Erasmus J.J.
        • et al.
        Effects of radiation therapy on the lung: radiologic appearances and differential diagnosis.
        Radiographics. 2004; 24: 985-997
        • Faruqi S.
        • Giuliani M.E.
        • Raziee H.
        • et al.
        Interrater reliability of the categorization of late radiographic changes after lung stereotactic body radiation therapy.
        Int J Rad Oncol Biol Phys. 2014; 89: 1076-1083
        • Ronden M.I.
        • van Sörnsen de Koste J.R.
        • Johnson C.
        • et al.
        Incidence of high-risk radiological features in patients without local recurrence following SABR for early-stage non-small cell lung cancer.
        Int J Radiat Oncol Biol Phys. 2018; 100: 115-121
        • Senthi S.
        • Dahele M.
        • van de Ven P.M.
        • Slotman B.J.
        • Senan S.
        Late radiologic changes after stereotactic ablative radiotherapy for early stage lung cancer: a comparison of fixed-beam versus arc delivery techniques.
        Radiother Oncol. 2013; 109: 77-81
        • Bourgouin P.
        • Cousineau G.
        • Lemire P.
        • Delvecchio P.
        • Hébert G.
        Differentiation of radiation-induced fibrosis from recurrent pulmonary neoplasm by CT.
        Can Assoc Radiol J. 1987; 38: 23-26
        • Libshitz H.I.
        • Sheppard D.G.
        Filling in of radiation therapy-induced bronchiectatic change: a reliable sign of locally recurrent lung cancer.
        Radiology. 1999; 210: 25-27
        • Kato S.
        • Nambu A.
        • Onishi H.
        • et al.
        Computed tomography appearances of local recurrence after stereotactic body radiation therapy for stage I non-small-cell lung carcinoma.
        Jpn J Radiol. 2010; 28: 259-265
        • Huang K.
        • Senthi S.
        • Palma D.A.
        • et al.
        High risk CT features for detection of local recurrence after stereotactic ablative radiotherapy for lung cancer.
        Radiother Oncol. 2013; 109: 51-57
        • Halpenny D.
        • Ridge C.
        • Hayes S.
        • et al.
        Computed tomographic features predictive of local recurrence in patients with early stage lung cancer treated with stereotactic body radiation therapy.
        Clin Imaging. 2015; 39: 254-258
        • Huang K.
        • Dahele M.
        • Senan S.
        • et al.
        Radiographic changes after lung stereotactic ablative radiotherapy (SABR) – can we distinguish recurrence from fibrosis? A systematic review of the literature.
        Radiother Oncol. 2012; 102: 335-342
        • Nguyen T.K.
        • Senan S.
        • Bradley J.D.
        • et al.
        Optimal imaging surveillance after stereotactic ablative radiation therapy for early-stage non-small cell lung cancer: findings of an International Delphi Consensus Study.
        Pract Radiat Oncol. 2018; 8: e71-e78
        • Hansell D.M.
        • Bankier A.A.
        • MacMahon H.
        • McLoud T.C.
        • Müller N.L.
        • Remy J.
        Fleischner Society: Glossary of Terms for Thoracic Imaging.
        Radiology. 2008; 246: 697-722
        • Verstegen N.E.
        • Maat A.P.
        • Lagerwaard F.J.
        • et al.
        Salvage surgery for local failures after stereotactic ablative radiotherapy for early stage non-small cell lung cancer.
        Radiat Oncol. 2016; 11: 131