Table 1:
Best-evidence papers
| Author, date, journal and country, study type (level of evidence) |
Patient group | Outcomes | Key results | Comments, study weaknesses |
|---|---|---|---|---|
| Huang et al., (2011), Eur J Cardiothorac Surg, China [2] Retrospective study |
Three hundred and twenty-nine patients with 436 lung tumours treated with RFA from 1999 to 2006 Primary (n = 237) Metastatic (n = 92) Inclusion criteria: (1) Aged 18–80 (2) Poor pulmonary function with FEV1 < 1 l, FEV1% <50%; MVV <50% and/or high cardiac risk (3) Refusal of surgery |
Median progression-free period Local progression 30-day mortality Overall survival: 1, 2 and 5 years Complications: Pneumothorax Haemoptysis Haemothorax Pneumonia Pericardial tamponade |
21.6 months 78/329 (23.7%) 0.6% 68.2, 35.5, 20.1% 63/329 (19.1%) 14/329 (4.2%) 10/329 (3.0%) 15/329 (4.5%) 3/329 (0.9%) |
RFA is a safe and well-tolerated procedure with confirmed efficacy in the treatment of malignant lung tumours Tumours >4 cm have a significantly increased risk of local progression Treatment-related complications were counted if within 30 days after RFA treatment |
| Beland et al., (2010), Radiology, USA [3] Retrospective study |
Seventy-nine patients with 79 tumours underwent RFA for primary NSCLC from 1998 to 2008 Stage IA n = 35 (78%) Stage IB n = 7 (16%) Stage IIIB n = 3 (7%) Adjuvant external beam radiation n = 19 (24%) Concomitant brachytherapy n = 9 (11%) Mean follow-up 17 months |
Residual tumour or recurrence Recurrence pattern: Local Intrapulmonary Nodal Mixed Distant metastases |
34/79 (43%) 38% 18% 18% 6% 21% 23 months |
RFA is a promising treatment option for primary lung cancer in non-surgical patients, however disease recurrence is common, occurring in 43% of patients At 2 years, local recurrence was the most common at 28%, suggesting that more aggressive initial RF ablation and adjuvant radiation may offer improvement in outcomes Potential for understaging of disease as patients did not undergo mediastinoscopy No standardized post-treatment follow-up imaging protocol |
| de Baère et al., (2006), Radiology, France [4] Prospective study |
Sixty patients with 97 treatable lung tumours underwent 74 RFA using CT guidance Patients who received systematic chemotherapy during follow-up period n = 22 Primary n = 9 (15%) Metastatic n = 51 (85%) |
Rate of incomplete local treatment per tumour at 18 months: Tumours <2 cm Tumours >2 cm Survival at 18 months: Overall Lung disease free Complications: Pneumothorax Alveolar haemorrhage Pleural effusion: Immediately after treatment 24–48 h after treatment FEV1 (L): Before treatment After treatment VC (L): Before treatment After treatment Post-procedure haemoptysis |
7% 5% 13% (P = 0.66) 71% 34% 40/74 (54%) 8/74 (11%) 7/74 (9%) 45/74 (60%) 0.62–3.65 0.72–3.65 (P = 0.65) 0.80–8.0 0.83–7.98 (P = 0.93) 7/74 (10%) |
RFA has high local success rates of complete ablation and curative treatment in inoperable primary and metastatic lung tumours and is well tolerated Ideal follow-up imaging to determine early treatment failure remains to be improved, probably including functional imaging and CT Small population Twenty-two patients received systemic chemotherapy for distant metastases during follow-up, hence difficult to evaluate the effect of such therapy on the rate of incomplete local treatment |
| Lencioni et al., (2008), The Lancet, Italy [5] Multicentre prospective trial |
One hundred and six patients with 183 biopsy-confirmed lung tumours <3.5 cm underwent RFA NSCLC (n = 33) Median follow-up 24 months |
Technical success Major complications: Pneumothorax Pleural effusion Complete tumour response lasting at least 1 year Overall survival (NSCLC): 1 year 2 years Cancer-specific survival (NSCLC): 1 year 2 years Stage I NSCLC: 2-year overall survival 2-year cancer specific survival |
99% n = 27 n = 4 88% 70% 48% 92% 73% 75% 92% |
Percutaneous CT-guided RFA yields high proportions of sustained complete ablation in patients with primary or secondary lung tumours, and is associated with acceptable morbidity Heterogeneous patient population Mean follow-up not long enough to detect late tumour recurrences PET scans not routinely used for the assessment of response |
| Hiraki et al., (2007), J Thorac Cardiovasc Surg, Japan [6] Retrospective study |
Twenty patients with Stage I NSCLC underwent RFA Median follow-up 21.8 months |
Local progression Local control rate: 1 year 2 years 3 years Mean survival Overall survival: 1 year 2 years 3 years Cancer-specific survival: 1 year 2 years 3 years Complications: Pneumothorax Pleural effusion |
7/20 (35%) 72% 63% 63% 42 months 90% 84% 74% 100% 93% 83% 13/20 (57%) 4/20 (17%) |
Treatment of Stage I NSCLC with one or more sessions of RFA offers promising outcomes in relation to survival. However, local progression rates are relatively high Short follow-up period Small study population |
| Pennathur et al., (2007), J Thorac Cardiovasc Surg, USA [7] Retrospective study |
Nineteen patients with Stage I NSCLC underwent RFA under CT-guidance Stage IA (n = 11) Stage IB (n = 8) Mean follow-up 29 months |
Local progression Initial complete response Partial response Overall survival: 1 year 2 years Complications: Pneumothorax |
8/19 (42%) 2/19 (10.5%) 10/19 (53%) 95% 68% 63% |
RFA appears to be safe in high-risk patients with stage I NSCLC, with reasonable results in terms of survival in high-risk patients who are not fit for surgical intervention Small sample size |
| Simon et al., (2007), Radiology, USA [8] Retrospective study |
One hundred and fifty-three patients with 189 tumours underwent 183 RFA sessions Primary (n = 116) Metastatic (n = 73) Stage I NSCLC (n = 75) Median follow-up 20.5 months |
(≤3 cm) Local tumour progression–free rates: 1 year 2 years 3 years 4 years 5 years (>3 cm) Local tumour progression–free rates: 1 year 2 years 3 years 4 years 5 years Difference between the survival rates: (≤3 cm) and (>3 cm) Overall survival rates: (NSCLC) 1 year 2 years 3 years 4 years 5 years Complications: Pneumothorax Chest tube insertion |
83% 64% 57% 47% 47% 45% 25% 25% 25% 25% (P < 0.002) 78% 57% 36% 27% 27% 28.4% 9.8% |
Lung RFA appears to be a safe treatment for Stage I NSCLC and is linked with promising long-term survival and local tumour progression outcomes Biopsies were not routinely performed during follow-up A proportion of patients treated concomitantly with systemic chemotherapy and/or external beam radiation therapy |
| Kashima et al., (2011), Am J Roentgenol, Japan [9] Retrospective study |
Four hundred and twenty patients with 1403 lung tumours underwent 1000 RFA sessions | Complications: Death Aseptic pleuritis Pneumonia Lung abscess Bleeding requiring transfusion Pneumothorax requiring pleural sclerosis Bronchopleural fistula Brachial nerve injury Tumour seeding Diaphragm injury |
0.4% 2.3% 1.8% 1.6% 1.6% 1.6% 0.4% 0.3% 0.1% 0.1% |
Lung RFA is a relatively safe procedure, but it can be fatal in few cases. Known risk factors such as age, tumour size, platelet count, previous systemic chemotherapy, previous external beam radiotherapy, emphysema should be used to stratify patients |
| Zemlyak et al., (2010), J Am Coll Surg, USA [10] Retrospective study |
Sixty-four patients with Stage I NSCLC SLR (n = 25) RFA (n = 12) PCT (n = 27) |
Overall 3-year survival: SLR RFA PCT 3-year cancer-specific survival: SLR RFA PCT 3-year cancer-free survival: SLR RFA PCT |
87.1% 87.5% 77% (P > 0.05) 90.6% 87.5% 90.2% (P > 0.05) 60.8% 50% 45.6% (P > 0.05) |
SLR, RFA and PCT are reasonable alternatives to lobectomy for patients who are poor candidates for major surgery. Survival at 3 years is comparable after sublobar resections and ablative therapies. Ablative therapies appear to be a reasonable alternative in high-risk patients not fit for surgery Small sample Selection bias SBRT not included in comparison |
| Lagerwaard et al., (2008), Int J Radiat Oncol Biol Phys, The Netherlands [11] Retrospective study |
Two hundred and six patients with Stage I NSCLC underwent SRT Medically inoperable (n = 167) Refused surgery (n = 39) Inclusion criteria: (1) Tumour <6 cm (2) Confirmed malignancy (cytohistologic or CT) (3) Absence of metastases on PET scan Prescription dose 60 Gy in three, five or eight fractions |
Median overall survival: 1-year survival rate 2-year survival rate Local recurrence: T1 T2 Overall recurrence DFS: 1 year 2 years Toxicity: Fatigue Chest wall pain Nausea Dyspnoea Cough Pneumonitis Rib fractures Chronic thoracic pain |
34 months 81% 64% 3.5% 2 /129 (1.6%) 5/90 (5.6%) (P = 0.13) 21% (43 patients) 83% 68% 31% 12% 9% 6% 6% 3% 2% 1% |
SRT is well tolerated in patients with extensive comorbidity presenting with inoperable Stage I NSCLC with high local control rates and minimal toxicity Median follow-up was only 12 months. Most recurrences occur within 2 years following treatment Only 88 patients attended for follow-up at 1 year Only a minority of the patients had pathologic confirmation of malignancy |
| Haasbeek et al., (2010), Cancer, The Netherlands [12] Retrospective study |
One hundred and ninety-three patients ≥75 years with 203 tumours treated using SRT T1 (n = 118) T2 (n = 85) 80% medically inoperable 20% declined surgery Median follow-up 12.6 months |
Survival rate: 1 year 3 years Median overall DFS: 1 year 3 years Complications: Fatigue Nausea Cough Dyspnoea Chest wall pain Rib fracture Grade ≥3 radiation pneumonitis Chronic chest wall pain Acute toxicity |
85.7% 45.1% 32.5 months 89.2% 72.6% 32.6% 4.1% 5.7% 5.2% 3.1% 1.6% 2.1% 2.6% 1.6% |
SRT achieved high local control rates with minimal toxicity in patients aged ≥75 years, suggesting it should be considered as a curative alternative in the treatment of NSCLC Median follow-up of 12.6 months not long enough |
| Le et al., (2006), J Thorac Oncol, USA [13] Retrospective study |
Thirty-two patients with inoperable lung tumours treated with single-fraction SRT NSCLC (n = 20) Metastases (n = 12) Tumour diameter 20–62 mm 15–30 Gy in one fraction 15 Gy (n = 9) 20 Gy (n = 1) 25 Gy (n = 20) 30 Gy (n = 2) Median follow-up 18 months |
Local progression: (NSCLC) >20 Gy <20 Gy CR rate: >20 Gy <20 Gy 1-year overall survival: (NSCLC) Toxicity: Fatigue Pneumothorax Grade 2–3 pneumonitis Pleural effusion |
9% 54% (P = 0.03) 57% 10% (P = 0.21) 85% 10/32 6/32 (19%) 4/32 (12.5%) 1/32 |
Single-fraction SRT is feasible for selected patients with lung tumours and higher doses (>20 Gy) are associated with improved local control. For those who have had prior thoracic radiotherapy, doses ≥25 Gy may be too toxic Short follow-up period Variation in treatment techniques (breath-holding vs. tracking) |
| Onishi H et al., (2004), Cancer, Japan [14] Retrospective study |
Two hundred and forty-five underwent hypofractionated high-dose STI between 1995 and 2003 BED ≥100 Gy (n = 173) BED 100 Gy (n = 72) Stage IA n = 155 Stage IB n = 9 Tumour diameter 7–58 mm (median, 28 mm) CT chest usually obtained 3-monthly for first year and repeated every 4–6 months thereafter Tumour response evaluated using previously published National Cancer Institute (NCI) criteria |
Local progression overall: BED ≥100 Gy BED 100 Gy Local disease recurrence: BED ≥100 Gy BED 100 Gy 3-year survival rate: BED ≥100 Gy BED 100 Gy Overall survival rates: 3 years 5 years Local tumour response: CR (completely disappeared/replaced by fibrotic tissue) PR (≥30% reduction in the maximum cross-sectional diameter) Overall response rate BED ≥100 Gy BED 100 Gy Toxicity: Radiation-induced pulmonary complications |
14.5% 8.1% 26.4% (P < 0.05) 13.5% 8.1% 26.4% (P < 0.01) 88.4% 69.4% (P 0.05) 56% 47% 57/245 (23.3%) 151/245 (61.6%) 84.8% 84.5% 83.3% 17/245 (6.9%) |
Hypofractionated high-dose STI is a feasible and effective curative treatment of patients with Stage I NSCLC Local control and survival rates better in patients treated with BED ≥100 Gy than for BED 100 Gy Treatment parameters heterogeneous |
| Timmerman et al., (2010) JAMA, USA [15] Multicentre prospective study |
Fifty-five patients with biopsy-proven peripheral T1-T2N0M0 NSCLC (measuring 5 cm in diameter) underwent SBRT T1 (n = 44) T2 (n = 11) Prescription dose 18 Gy per fraction ×3 fractions (54 Gy total) Median follow-up 34.4 months |
Median overall survival Overall 3-year survival Disseminated recurrence at 3 years 3-year primary tumour control rate Local-regional control rate DFS Adverse events: Grade 3 Grade 4 |
48.1 months 55.8% 22.1% 97.6% 87.2% 48.3% 7/55 (12.7%) 2/55 (3.6%) |
SBRT is an effective treatment in patients with inoperable NSCLC, with high rates of local tumour control and moderate treatment-related morbidity Rarely used invasive pathological staging and histological confirmation of recurrence, lowering accuracy |
| Fakiris et al., (2009), Radiat Oncol Biol Phys, USA [16] Retrospective study |
Seventy patients with biopsy confirmed NSCLC underwent SBRT T1 (n = 34) T2 (n = 36) Prescription dose: 60–66 Gy in three fractions Median follow-up 50.2 months |
Local control at 3 years Local recurrence Nodal recurrence Distant recurrence Median survival 3-year overall survival Median survival: T1 tumours T2 tumours |
88.1% 4/70 (5.7%) 6/70 (8.6%) 9/70 (12.9%) 32.4 months 42.7 months 38.7 months 24.5 months (P = 0.194) |
Treatment with SBRT results in high rates of local control in medically inoperable patients with Stage I NSCLC |
| Timmerman et al., (2006), J Clin Oncol [17] Prospective study |
Seventy patients underwent SBRT for NSCLC Treatment dose: 60 to 66 Gy total in three fractions during 1–2 weeks Median follow-up 17.5 months |
2-year overall survival 3-month major response rate Local control 2 years: Deaths due to: Cancer Treatment Comorbid illness Median overall survival Toxicity: Grade 1–2 Grade 3–4 Grade 5 (death) |
54.7% 60% 95% n = 5 n = 6 n = 17 32.6 months n = 58 n = 8 n = 6 |
Local recurrence and toxicity occur late after this treatment; however, this regimen should not be used for patients with tumours near the central airways due to excessive toxicity Short follow-up period This trial did not define a limit on the period of observation of toxicity related to therapy-hospitalizations/deaths occurring more than a year after therapy might not have been attributed to SABR |
NSCLC: non-small-cell lung cancer; RFA: radiofrequency ablation; FEV1: forced expiratory volume in 1 s; VC: vital capacity; DFS: disease-free survival; MVV: maximum voluntary ventilation; SLR: sublobar resection; PCT: percutaneous cryoablation therapy; SRT: stereotactic radiotherapy; SBRT: stereotactic body radiation therapy; STI: stereotactic irradiation; BED: biologic effective dose; CR: complete resolution; PR: partial resolution; MTD: maximum tolerated dose.