Elsevier

The Lancet Oncology

Volume 9, Issue 7, July 2008, Pages 621-628
The Lancet Oncology

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Response to radiofrequency ablation of pulmonary tumours: a prospective, intention-to-treat, multicentre clinical trial (the RAPTURE study)

https://doi.org/10.1016/S1470-2045(08)70155-4Get rights and content

Summary

Background

Radiofrequency ablation is an accepted treatment for non-surgical patients with liver cancer. The purpose of this study was to identify the feasibility, safety, and effectiveness of percutaneous radiofrequency ablation of malignant lung tumours.

Methods

Between July 1, 2001, and Dec 10, 2005, a series of 106 patients with 183 lung tumours that were 3·5 cm in diameter or smaller (mean 1·7 cm [SD 1·3]) were enrolled in a prospective, intention-to-treat, single-arm, multicentre clinical trial from seven centres in Europe, the USA, and Australia. Proof of malignancy was obtained by biopsy in all patients. Diagnoses included non-small-cell lung cancer (NSCLC) in 33 patients, metastasis from colorectal carcinoma in 53 patients, and metastasis from other primary malignancies in 20 patients. All patients were considered by the treating physician to be unsuitable for surgery and unfit for radiotherapy or chemotherapy. Patients underwent radiofrequency ablation in accordance with standard rules for CT-guided lung biopsy and were then followed for up to 2 years. Primary endpoints were technical success (defined as correct placement of the ablation device into all tumour targets with completion of the planned ablation protocol), safety (including identification of treatment-related complications and changes in pulmonary function), and confirmed complete response of tumours (according to modified Response Evaluation Criteria in Solid Tumors). Secondary endpoints were overall survival, cancer-specific survival, and quality of life. This trial is registered with ClinicalTrials.gov, number NCT00690703.

Findings

Correct placement of the ablation device into the target tumour with completion of the planned treatment protocol was feasible in 105 (99%) of 106 patients. The technical failure in one patient was caused by the inability to place the device inside a small tumour. No procedure-related deaths occurred in any of the 137 ablation procedures. Major complications consisted of pneumothorax (n=27) or pleural effusion (n=4), which needed drainage. No significant worsening of pulmonary function was noted. A confirmed complete response of target tumours lasting at least 1 year was shown in 75 (88%) of 85 assessable patients. No differences in response were noted between patients with NSCLC or lung metastases. Overall survival was 70% (95% CI 51–83%) at 1 year and 48% (30–65%) at 2 years in patients with NSCLC, 89% (76–95%) at 1 year and 66% (53–79%) at 2 years in patients with colorectal metastases, and 92% (65–99%) at 1 year and 64% (43–82%) at 2 years in patients with other metastases. Cancer-specific survival was 92% (78–98%) at 1 year and 73% (54–86%) at 2 years in patients with NSCLC, 91% (78–96%) at 1 year and 68% (54–80%) at 2 years in patients with colorectal metastases, and 93% (67–99%) at 1 year and 67% (48–84%) at 2 years in patients with other metastases. Patients with stage I NSCLC (n=13) had a 2-year overall survival of 75% (45–92%) and a 2-year cancer-specific survival of 92% (66–99%).

Interpretation

Percutaneous radiofrequency ablation yields high proportions of sustained complete responses in properly selected patients with pulmonary malignancies, and is associated with acceptable morbidity. Randomised controlled trials comparing radiofrequency ablation with standard non-surgical treatment options are warranted.

Funding

Angiodynamics (Queensbury, NY, USA).

Introduction

Lung cancer is the leading cause of cancer death in both men and women.1 Non-small-cell lung cancer (NSCLC) constitutes about 80% of primary malignant tumours in the lung.2 Surgical resection is the standard of care for early-stage NSCLC and offers 5-year survival in excess of 50% for all non-small-cell histological groups.2, 3 Careful preoperative assessment of the patient's overall medical condition, especially the pulmonary reserve and the associated comorbidities, is crucial for considering the benefits of surgery.4, 5 Patients with early-stage disease who are medically unfit for surgery, but who have sufficient pulmonary reserve, might be candidates for radiotherapy with curative intent.6 In two large radiotherapy series, patients ineligible for surgery who were treated with definitive radiotherapy achieved a 5-year survival of 10% and 27%.7, 8

The lungs are the second most frequent site of metastatic disease. Many series have documented survival benefits of surgical resection in selected patients with pulmonary metastases of favourable histology—especially colorectal carcinoma.9, 10 Unfortunately, only a few patients are suitable candidates for resection because of the associated extrapulmonary disease, the extent and location of lesions in the lungs, or concurrent medical conditions. Moreover, the high risk of recurrence and the need to remove functioning lung tissue along with the lesions restricts indications for surgery.11

Percutaneous image-guided radiofrequency ablation is a minimally invasive technique used to treat solid tumours. Because of its ability to produce large volumes of coagulation necrosis in a controlled fashion, this technique has gained acceptance as a viable therapeutic option for unresectable liver malignancies.12, 13 Recently, single-institution case series have suggested that radiofrequency ablation can be a valuable treatment option for patients with unresectable or medically inoperable lung malignancies.14, 15, 16 However, to our knowledge, this technique has never been tested in the setting of a large, intention-to-treat clinical trial. In 2001, we designed a multicentre clinical trial aimed at assessing the feasibility, safety, and effectiveness of percutaneous CT-guided radiofrequency ablation in the treatment of NSCLC and pulmonary metastases.

Section snippets

Patients

This study was designed as a prospective, intention-to-treat, single-arm, multicentre clinical trial. Inclusion criteria were: age greater than 18 years; biopsy-proven NSCLC or lung metastasis; patients rejected for surgery and considered unfit for radiotherapy or chemotherapy; up to three tumours per lung, each 3·5 cm or smaller in greatest diameter, detected by CT; tumours located at least 1 cm from trachea, main bronchi, oesophagus, aorta, aortic arch branches, main, right, or left pulmonary

Results

Between July 1, 2001, and Dec 10, 2005, 106 patients (36 women and 70 men; median age 66 years [range 29–85]; mean 64·9 years [SD 11·6]) with 183 malignant lung tumours were enrolled in seven centres in Europe, the USA, and Australia. Median tumour size was 1·5 cm (range 0·5–3·4; mean 1·7 cm [SD 0·8]). Proof of malignancy for at least one lesion was obtained in all patients. Diagnoses included NSCLC in 33 patients, metastasis from colorectal adenocarcinoma in 53 patients, and metastasis from

Discussion

Our study shows that percutaneous CT-guided radiofrequency ablation yields high proportions of sustained CR in properly selected patients with primary or secondary lung malignancies, and is associated with acceptable morbidity.

The aim of radiofrequency ablation is to induce thermal injury to the target tumour by electromagnetic energy deposition. The patient is part of a closed-loop circuit, that includes the radiofrequency generator, an active electrode placed inside the tumour, and a large

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