Rationale and Objectives
The aim of the study was to evaluate the overall survival (OS) rate, progression survival rate, and local control rate over 10 years of medically inoperable patients with lung cancer undergoing computed tomography (CT)-guided radiofrequency ablation (RFA).
Materials and Methods
Between September 2004 to March 2016, 668 neoplasms were treated in 476 medically inoperable patients (294 men, 60 women; median age 74 years; range 29–84) who underwent CT-guided RFA. All patients had clinical or pathologic evidence of the neoplastic lesion: 22.1% patients with primary non–small cell lung cancer (NSCLC), 22.3% patients with recurrent NSCLC, 45.2% with metastases, and 10.3% with small cell lung cancer. The mean size of the lesions was 3.8 cm (range of 1–16 cm). Twenty-one lesions were re-treated from one to as many as four times.
Results
The procedure was technically successful in all cases. No procedure-related deaths occurred in the RFA procedures. Major complications consisted in 104 (21.8%) cases of low-grade fever, 46 (9.6%) of the pneumothorax. The mean follow-up was 32 months. The probabilities of 1-, 2-, 3-, 5-, and 10-year OS rate were 98.1%, 86.6%, 68.9% 34.5%, and 9.5% for primary NSCLC; 59.7%, 18.5%, 8%, 3.4%, and 1.5% for metastases; 93.3%, 59.1%, 49.6%, 19.7%, and 0% for recurrence; and 89.4%, 67.5%, 39.1%, 16.5%, and 0% for small cell lung cancer. In primary NSCLC, progression-free survival (PFS) and OS were significantly related to tumor size, but there was no significant difference in recurrent NSCLC, metastasis, and peripheral SCLC. The median OS of metastases of NSCLC was significantly related to nodal or distant metastases. The most common pattern of recurrence was local; any type of recurrence at 1-year follow-up imaging was seen in 7.1% of primary NSCLC diameter less than 3 cm.
Conclusions
Our experience indicates that CT-guided RFA done by the thoracic surgeons is feasible and safe in high-risk patients. Maximum tumor diameter less than 3 cm and lack of extrapulmonary metastasis are all positive prognostic factors of survival after RFA. RFA offers good local control of recurrent NSCLC, lung metastases, and SCLC, also in the long-term period. RFA should continue to offer an alternative option in medically inoperable patients.
Introduction
Lung cancer is the deadliest and most common cancer, with an annual incidence of 1.6 million new cases of lung cancer occurring, accounting for 13% of all cancers, and 1.4 million people die of the disease, representing 18% of all cancer deaths worldwide . Lobectomy is still the gold-standard treatment for selected non–small cell lung cancer (NSCLC); however, several studies reported that the number of patients who are not candidates for curative surgical resection because of coexistent older age, poor lung function, cardiorespiratory co-morbidity, or other associated diseases is increasing. Additionally, the lungs are one of the most common sites of metastases; almost 30% of patients with lung cancer will develop metastases. Traditional chemotherapy radiotherapy and new gene target therapy for medically inoperable patients, patients with recurrent cancer after other local treatment, or patients with metastases have limited benefits only, especially in young patients .
For these reasons, several nonsurgical treatments were developed, like radiofrequency ablation (RFA), which has been widely used in treatment of pulmonary tumors. A good local response, with a very low rate of complications, and an elevated tolerability, was reported in clinical trials . These trials have a short follow-up period of RFA in the middle term, but few long-term outcomes have been reported . Lack of guidelines for thermal ablation of primary and metastatic lung tumors is the new problem.
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Materials and Methods
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Selection of Patients
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Treatment Protocol
Patient Preparation
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Procedural
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Post-procedure Follow-up
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Data Collection and Statistical Analysis
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Results
Patient Characteristics
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TABLE 1
Demographic and Clinical Characteristics of the Study Population
Patients ( n = 476) Gender: Male 294 Female 182 Age (y) : Mean: 69 Median 74 Range: 29–88 Size Average 3.8 cm Range: 1 cm–16 cm Lesions were treated with RFA 513 Histology Adenocarcinoma 220 Squamous 115 Bronchoalveolar carcinoma 32 Small cell lung cancer 49 Other carcinoma 60 Liver cancer 11 Breast cancer 14 Brain cancer 2 Rectal carcinoma 11 Renal cell carcinoma 5 Esophageal squamous cell carcinoma 13 Others 4
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Complication and Treatment
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Response to Treatment
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Progression-free Survival
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TABLE 2
Progress-free Survival Comparison by Different Patients with Lung Cancer \*
Different Patients Progress-free Rate % Median for Progress-free Survival Time Total n Censored n Percent% 6 mo 12 mo 24 mo 36 mo 60 mo Estimate 95% Confidence Interval Lower Bound Upper Bound Primary NSCLC cT ≤ 3cmN0M0 42 14 33.3% 95.2% 92.9% 80.9% 48.1% 31.4% 36 26.2 45.8 cT > 3cmN0M0 63 18 28.6% 95.2% 79% 53.5% 22.7% 18.2% 26 19.9 32.1 ALL 105 32 30.5% 95.2% 84.5% 64.4% 32.5% 20.3% 31 28.3 33.8 Metastases Distant metastases of NSCLC cTN1-3M0 89 29 32.6% 82.8% 24% 7.4% 2.5% 0 9 7.9 10.1 cTN0-3M1 66 17 25.8% 76.4% 18.1% 0 0 0 9 7.9 10.1 ALL 155 46 29.7% 79.8% 20.6% 4.1% 1.4% 0 9 8.4 9.6 Intrapulmonary metastases of other tumors 61 13 21.3% 81.3% 24.9% 3.3% 1.2% 0 9 7.6 10.4 ALL 216 59 27.3% 78.8% 22% 4.4% 1.1% 0 9 8.4 9.6 Recurrent NSCLC 106 33 31.1% 96.2% 65.5% 38% 20.4% 4.3% 17 11.7 22.3 Small cell lung cancer 49 4 8.2% 73.3% 31.1% 6.7% 2% 0 10 7.4 12.7 Overall 476 128 26.9% 86.9% 49.6% 28.5% 13.8% 8.7% 12 10.7 13.3
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![Figure 2, Kaplan-Meier survival analysis of all patients demonstrated median overall survival (OS) and progress-free survival (PFS) to be 24 months (95% confidence interval [CI] 22.0–26.0 months) and 12 months (95% CI 10.7–13.3 months) ( a, b ); compared OS and PFS between primary non–small cell lung cancer (NSCLC), recurrent NSCLC, metastatic NSCLC, and small cell lung cancer (SCLC) in ( c, d ), compared between Ct ≤ 3cmN 0 M 0 and cT > 3cmN 0 M 0 ( e, f ), between cTN1-3M0 and cTN0-3M1 in ( g, h ), and compared distant metastases between intrapulmonary metastases ( i, j ).](https://storage.googleapis.com/dl.dentistrykey.com/clinical/LongtermObservationofCTguidedRadiofrequencyAblationofLungNeoplasmin476ConsecutivePatientsbyaThoracicSurgicalService/1_1s20S1076633217303240.jpg)
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Recurrence Patterns Analysis
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TABLE 3
Probability of NSCLC Recurrence After RF Ablation
ALL T ≤ 3cmN0M0 T > 3cmN0M0 Primary NSCLC Recurrent NSCLC Metastases Recurrence pattern 6 M (%) 1 Y (%) 2 Y (%) 6 M (%) 1 Y (%) 2 Y (%) 6 M (%) 1 Y (%) 2 Y (%) 6 M (%) 1 Y (%) 2 Y (%) 6 M (%) 1 Y (%) 2 Y (%) 6 M (%) 1 Y (%) 2 Y (%) All 13.1% 50.4% 71.5% 4.8% 7.1% 19.1% 4.8% 21% 46.5% 4.8% 15.5% 35.6% 3.8% 34.5% 60.0% 19.8% 78.9% 96% Local 4.7% 17.0% 24.5% 4.8% 7.1% 11.9% 4.8% 16.2% 23.3% 4.8% 12.6% 18.8% 1.9% 11.2% 23.8% 5.4% 23.0% 27.5% Intrapulmonary 1.8% 7.3% 12.5% 0 0 2.4% 0 1.6% 6.6% 0 1.0% 4.9% 1.0% 6.1% 16.6% 2.1% 10.6% 12.8% Any nodal 3.8% 11.1% 16.3% 0 0 4.8% 0 3.2% 11.6% 0 2.0% 8.9% 1.0% 7.1% 10.3% 7.0% 17.4% 21.8% Distant 2.3% 9.7% 12.3% 0 0 0 0 0 1.7% 0 0 1.0% 0 7.1% 7.2% 4.8% 18.0% 22.4% Mix 0.5% 5.3% 6.8% 0 0 0 0 0 3.3% 0 0 2.0% 0 3.0% 2.1% 0.54% 10.0% 11.5%
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Treatments After Initial RFA and Lung Progression
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Overall Survival
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TABLE 4
Overall Survival Comparison by Different Patients with Lung Cancer \*
Patients Survival Rate % Median for Survival Time Total n Censored n Percent% 12m 24m 36m 60m 120m Estimate 95% Confidence Interval Lower Bound Upper Bound Primary NSCLC cT ≤ 3cmN0M0 42 15 35.7% 100% 95.2% 87.2% 43.2% 9.5% 57 51.6 62.4 cT > 3cmN0M0 63 11 17.5% 98.4% 80.8% 56.6% 28.8% 2% 30.5 31.0 55.5 ALL 105 26 24.8% 98.1% 86.6% 68.9% 34.5% 9.5% 51 43.8 58.2 Metastases Distant metastases of NSCLC cTN1-3M0 89 11 12.4% 76.8% 30.3% 10.2% 2.2% 0 17 15.0 19.0 cTN0-3M1 66 4 6.1% 29.7% 9.2% 1.8% 1.8% 1.8% 7 5.8 8.2 ALL 155 15 9.7% 56.8% 17.4% 7.6% 2.3% 1.1% 14 12.4 15.7 Intrapulmonary metastases of other tumors 61 10 16.4% 63.4% 21.4% 11.8% 2.9% 0 15 13.2 18.7 ALL 216 25 11.6% 59.7% 18.5% 8% 3.4% 1.5% 14 12.5 15.5 Recurrence NSCLC 106 28 26.4% 93.3% 59.1% 49.6% 19.7% 0 31 25.1 36.9 Small cell lung cancer 49 11 22.4% 89.4% 67.5% 39.1% 16.5% 0 32 25.7 38.2 Overall 476 90 18.9% 76.8% 47.3% 31.0% 15.7% 3.7% 24 22.0 26.0
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TABLE 5
Survival Comparison by Different Treatment of Patients with Lung Cancer \*
Different Treatment Survival Rate % Median for Survival Time Treatment_n_ 12 mo 24 mo 36 mo 60 mo 120 mo Estimate 95% Confidence Interval Lower Bound Upper Bound RFA 146 61.7% 39.4% 28.8% 11.3% 2.5% 16.000 12.655 19.345 RFA + TKI 48 80.1% 50.7% 39.2% 19.2% 5.5% 26.000 19.545 32.455 RFA + chemotherapy 208 83.8% 51.3% 31.8% 14.1% 1.5% 25.000 21.347 28.653 RFA + radiotherapy 48 77.6% 48.8% 23.8% 12.6% 0 24.000 21.832 26.168 RFA + TKI + chemoradiotherapy 26 92.3% 80.8% 64.4% 45.8% 3.2% 68.000 41.259 94.741 Overall 476 76.8% 47.3% 31.0% 15.7% 3.7% 24.000 22.017 25.983
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Discussion
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Acknowledgment
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Supplementary Data
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Appendix S1
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