Table 3.
Lung stereotactic ablative body radiotherapy toxicity
| Study | Scale | Gd 1 | Number | Gd 2 | Number | Gd 3 | Gd 4+ |
|---|---|---|---|---|---|---|---|
| Navarro–Martin et al 201643 | CTCAE V3 | 89% Gd 1 acute 100% chronic Gd 1 Pneumonitis (68%) |
34 42 26 |
16% acute 2 pleuritis 1 dyspnoea 1 cough 1 dermatitis 1 pneumonitis 18% chronic Dyspnoea Pneumonitis Cough Dermatitis Anorexia |
6 7 |
1 Gd 3 pneumonitis (5%) 1 chronic AF and dyspnoea |
1 Gd 5 (developed late from Gd 3 toxicity −2.65)—Pt thought to have subclinical ILD |
| Heseltine et al 201641 | Not reported | 13 Gd 3+ events (12%) Significantly more Gd 3+ events in those pts with GTV <1 cm from PBT |
4 potential Gd 5 events 2 pneumonia 2 pulmonary haemorrhage (both previous exposure to bevacizumab) |
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| Shaverdian et al 201642 | CTCAE v3 | 88% reported no ≥ Gd 2 toxicity | ≥Gd 2 toxicity in 12% Pneumonitis (9%) Rib# (3%) |
8 3 |
2 pneumonitis Gd 3 | No Gd 3+ toxicity reported | |
| Chang et al 201545 | NCI-CTC V3 | SABR 3 pts (10%) 2 cough/dyspnoea 3 Chest wall pain 1 fatigue and rib# Surgery 12 pts (44%)4 Gd 3 dyspnoea 2 Gd 3 pneumonia 4 Gd 3 chest pain |
No Gd 4 or above in SABR arm Sx arm—1 Gd 5 death from surgical complications 12 Gd 3–4 Surgery 12 pts (44%) 1 Gd 4 dyspnoea |
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| Murray et al 201546 | NCI-CTC V4 | Acute—1 Gd 3 dyspnoea 4 Gd 3 fatigue Delayed (>6 weeks, <12 weeks) 1 Gd 3 cough 10 Gd 3 dyspnoea 3 Gd 3 fatigue 1 Gd 4 fatigue Late (>12 weeks) 8 Gd 3 dyspnoea 1 Gd 3 pneumonitis |
No grade 4 toxicity during tx 1 pt died within 30 days of SABR, but CoD unknown; had been asymptomatic (potential Gd 5) 1 patient died at 12 weeks from COPD |
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| Nagata et al 201540 | CTCAE V3 | Inop—Gd 3 11 (10.6%) Dyspnoea 10 Hypoxia 8 Pneumonitis 8 Chest pain 2 Cough 1 Op—Gd 3 4 (6.2%) Dyspnoea 2 Hypoxia 1 Pneumonitis 1 |
No Gd 5 toxicity reported Gd 4 inop—2 pts 2 Dyspnoea 1 Hypoxia 1 pneumonitis No Gd 4 toxicity in operable pts. |
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| Gillespie et al 201547 | CTCAE V2 | Over 3 studies Acute Gd 2 range 8.7–19% | Gd 3 toxicity range 0–2% | No Gd 4 or 5 toxicity reported | |||
| Palma et al 201252 | CTCAE V3 | Common Gd 1/2–55% Fatigue Dyspnoea/cough Chest wall pain Nausea/appetite |
55 24 18 10 |
Acute—1 pt developed Gd 3 pneumonitis late (>6 weeks)—2 pts Gd 3 pneumonitis 2 pts rib# 1 pt haemoptysis |
No Gd 4 or 5 toxicity reported | ||
| Chang et al 201248 | CTCAE v3 | Oesophagitis 1.5% | 2 | Chest wall pain (8.5%) Pneumonitis (9.2%) |
12 15 |
1 Chest wall pain Gd 3 (0.8%) 8 Dermatitis Gd 2/3 (6.2%) 3 Pneumonitis Gd 3 (2.3%) |
No reported Gd 4 or 5 toxicity |
| Taremi et al 201250 | CTCAE V3 | 29% denied any acute toxicity 31% denied late toxicity |
Late—rib# (14.8%) Mostly asymptomatic |
16 | Acute Gd 3–4 (3.7%) 1 Fatigue 2 Dyspnoea 1 Chest wall pain Late Gd 3 (>3 months)—6 pts 3 rib# 2 Dyspnoea 1 Pneumonia |
No grade 4 or 5 toxicity reported | |
| Bongers et al 201153 | CTCAE v4 | Chest wall pain Gd 1–2 (5.4%) | 27 | 5 Chest wall pain Gd 3 (1%) 8 rib# (1.6%) |
Not reported | ||
| Bral et al 201154 | NCI-CTC V3/RTOG | Dyspnoea (12%) | 2 | Gd3—8 pts (20%) Pneumonitis 2 (12%) Cough 2 (12%) Stenosis 1 (10%) |
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| Andratschke et al 201155 | NCI-CTC V3 | Radiological pneumonitis (34.8%) | 32 | Pneumonitis (13%) | 12 | Pneumonitis 2 (2.2%) Dyspnoea 7 (7.3%) |
Gd 4 dyspnoea—4 (4.1%) |
| Haasbeek et al 201156 | CTCAE v3 | Gd 0 or 1 acute Gd 0 or 1 late |
56 50 |
Gd 2 acute (10%) Grade 2 late (14%) |
6 9 |
1 Gd 3 acute (2%) 4 Gd 3 late (6%) |
No Gd 4 or 5 toxicity reported |
| Haasbeek et al 201057 | RTOG acute toxicity RTOG/EORTC late toxicity |
116 patients reported no acute toxicity | 32% fatigue | Late—4 pts Gd 3–4 pneumonitis (2.1%) 3 pts rib# (1.6%) Chest wall pain 5 pts (2.6%) 3 pts non-malignant effusion |
No grade 5 toxicity reported | ||
| Timmerman et al 201058 | NCI-CTC V3 | 7 pts reported Gd 3 (12.7%) 2 reduced FEV1 2 Hypoxia 2 Pneumonitis 3 PFTS altered 2 pts reported Gd 4 (3.6%) 1 hypocalcaemia 1 Pulmonary |
No Gd 5 toxicity reported | ||||
| Grills et al 201060 | NCI-CTC V3 | Chest wall pain—9 (9.8%) | 9% pneumonitis 6% rib# 4% chronic dyspnoea |
Rib# 3 (3.3%) | 2% pneumonitis Dyspnoea Myositis |
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| Ricardi et al 201061 | RTOG acute and late | Fatigue 15% Skin erythema 10% Dyspnoea and cough 10% Chest pain 7% |
3 pts had chronic pain (4.8%) | 2 patients had Gd 3 radiation pneumonitis (3.2%) | |||
| Bradley et al 201033 | CTCAE V3 | 3 pts Gd 2 pneumonitis 4 pts rib pain or # |
1 pt developed brachial plexopathy | ||||
| Baumann et al 200963 | NCI-CTC V2 | 16 (28%) | 1 Gd 4 dyspnoea No Gd 5 |
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| Fakiris et al 200964 | NCI-CTC V2 | Gd 3 pneumonia 1 Pleural effusion 2 Pts 2 Gd 4 apnoea |
Gd 5 (possible) Pneumonia 3 Haemoptysis 1 Resp failure 1 |
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| Lagerwaard et al 200865 | – | 51 % No toxicity Fatigue 31% Chest wall pain 12% Nausea 9% Dyspnoea 6% Cough 6% |
Gd 3–6 pts (3%)—pneumonitis 4 rib fractures 3 chronic pain |
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| Chen et al 200836 | NCI-CTC/RTOG | 28% had no reported toxicity 7 pts Gd 1 bone marrow toxicity |
3.1% Gd 2 toxicity Bone marrow |
No Gd 3 toxicity | |||
| Onishi et al 200737 | NCI-CTC v2 | Cough/dyspnoea Gd 1 | 28 (10.9%) | Gd 2 pneumonitis—14 pts (5.4%) | Gd 3–6 pts pneumonitis requiring O2 3 oesophagitis 3 pts skin reaction (1.2%) 4 pts rib# (1.6%) |
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| Koto et al 200766 | NCI-CTC v3 | 24 pts Gd 1 pneumonitis | Gd 2 pneumonitis 3 pts | Gd 3 pneumonitis in 1 pt 1 pt lobar collapse |
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| Hoyer et al 200667 | WHO PS and Tox | 8 Gd 1–2 dyspnoea 6 Gd 1–2 nausea 14 Gd 1–2 pain |
3 Gd 3 dyspnoea 2 Gd 3 pain 1 Gd 4 dyspnoea |
1 death due to pneumonia felt unrelated to treatment | |||
| Nyman et al 200668 | RTOG acute/late | 9 pts skin reaction (20%) oesophagitis in 4 pts (9%) 4 pts had transient chest pain 4 pts had pneumonia/infections 3 pts had cough |
51% did not have any toxicity | 2 pts had rib# 3 pts atelectasis |
No pneumonitis reported | ||
| Nagata et al 200569 | NCI-CTC v2 | 10 pts Gd 1 cough or malaise (22%) | 2 pts Gd pneumonitis | No Gd 3 toxicity reported | |||
| McGarry et al 200570 | NCI-CTC | 4 Gd 2 pts—bronchitis, pericardial effusion, pneumonitis, distant pneumonia | 6 Gd 3 pts—2 pneumonitis, tracheal necrosis, hypoxia, dermatitis, pericardial effusion | 1 pt Gd 4 pneumonitis 72 Gy/3# | |||
| Zimmermann et al 200571 | CTC-RTOG RTOG late |
Gd 1–2—fatigue 20 % 1 pt pain, fever, pneumonia. 8 pts Gd 1, 5 pts Gd 2 pneumonitis 1 nausea and dermatitis Gd 1 |
1 Gd 3 pneumonitis (3%) |
AF, atrial fibrillation; CoD, cause of death; COPD, Chronic Obstructive Pulmonary Disease; CTC, common toxicity criteria; FEV1, forced expiratory volume in 1 second; Gd, grade; ILD, interstitial lung disease; inop, inoperable; NCI, national cancer institute; op, operable; PBT, proximal bronchial tree; PFTs, pulmonary function tests; Pt, patient; resp, respiratory; rib#, rib fracture; RTOG, Radiation Therapy Oncology Group; Sx, surgical; tx, treatment; WHO, World Health Organisation.