Radiofrequency Ablation For Treatment Of Peripheral Non
Operable Non Small Cell Lung Cancer
Mohamed Khairy El-Badrawy**, Adel El-Badrawy*, Amany Zeidan**, Saleh El-Essawy*,
Omaima Badr**, Mohamed Awad***
Radiology*, Thoracic Medicine**, Oncology*** DepartmentsMansoura Faculty of Medicine
Egypt
Lung cancer is the leading cause of
cancer-related mortality in both men
and women in the US.
It causes more death than colorectal
cancer, breast cancer, and prostate
cancer combined.
Non-small-cell lung cancer (NSCLC)
constitutes about 80% of primary
malignant tumors in the lung.
Although surgical resection remains the
mainstay of therapy for early stage non–
small cell lung cancer (NSCLC), most
patients present with advanced disease.
In addition, many patients with
respectable early stage disease are unfit
for surgical lung resection.
Tumor destruction with heating
• The capability of heat to kill cancerous cells has been known for several decades.
• Tumor cells are more sensitive to heat than normal tissue and temperatures as low as 41°C can destroy caner cells.
(Dupuy et al., 2006).
Ablative therapies
• Many ablative therapies had been studied as minimally invasive alternatives to surgery in patients unfit for surgery or with advanced disease.– Anticipated reduced morbidity and mortality, – Low cost, – Suitability for real-time imaging guidance, – Can be done on an outpatient basis .
Advantages of RFA
• Radiofrequency ablation (RFA) has become the imaging-guided ablative method of choice because of:– its relatively low cost, – its capability of creating large regions of
coagulative necrosis and – its relatively low toxicity
(Abbas et al., 2007).
Heat-based ablative methods
• Heat-based ablative methods such as:– Radio-frequency (RF) ablation, – Microwave ablation, – Laser ablation
(Dupuy et al., 2000).
Technique of RFA
• RFA involves the application of high-frequency alternating current to heat and coagulate target lesions. RFA systems have three components
– A generator – An active electrode that is placed within the tumor – A dispersive electrode (bovie pad) placed on the
thighs of the patient.
Schaefer et al., 2003):
Theory of RFA
• As the radiofrequency energy moves from the active electrode to the dispersive electrode and then back to the active electrode, ions within the tissue oscillate, resulting in frictional heating of the tissue.
• As the temperature within the tissue rises to greater than 60 ○C, instantaneous cell death occurs because of protein denaturation and coagulation necrosis
)Fernando et al., 2005.(
Guidance in RFA
• Advances in CT and US technology allows accurate localization of an electrode.
• Refinement of the electrode was necessary to deliver a well-defined area of thermal energy to larger volumes of tumor tissue.
RFA in lung cancer
• Patients not candidates for surgery owing to poor cardio-respiratory reserve,
• RF ablation alone or followed by conventional radiation therapy with or without chemotherapy may prove to be a treatment option
(Dupuy and Goldberg., 2001).
RFA in metastasis
• Ablation of a small tumor
• Size reduction of larger tumors.
• Palliation of chest wall or osseous metastatic tumors
(Hiraki et al., 2006).
Components of RFA system; active electrode in tumor, dispersive electrodes (bovie pads), and generator.
FDA approval of RFA
There are three FDA–approved devices available for the performance of RFA (Steinke et al., 2004):Boston Scientific (Boston, MA),RITA (Mountainview, CA),Valley Laboratory (Boulder City, CO).
RFA electrodes• The electrode is available in varied lengths and has an insulated shaft
and an uninsulated active tip that emits the RF current. 1. Tumors larger than 4 cm are treated with a cluster RF electrode that
consists of three 17-gauge RF electrodes spaced 5 mm apart. 2. Tumors smaller than 4 cm are treated with a single RF electrode.3. Tumors smaller than 2 cm are treated with a 1-cm-long active tip, 4. Those between 2 and 3 cm are treated with a 2-cm-long active tip, 5. Those between 3 and 4 cm are treated with a 3-cm-long active tip.
• The RF electrode is positioned with the electrode shaft parallel to the longitudinal axis of the tumor.
• The tip of the RF electrode is positioned against the deepest margin of the tumor for the first treatment.
• Axial and craniocaudal placement of the RF electrode is confirmed with CT fluoroscopy (5-mm collimation, 10 mA) (Zagoria et al., 2001).
Operative technique
1. Sedation and anaesthesia: • Conscious sedation (achieved with intravenous administration
of midazolam and fentanyl • General anesthetic may be required • Local anesthesia is achieved with injection of a 1% lidocaine
both intradermally and into deeper tissues
2. Patients are monitored for O2 sat, ECG, and BP.3. CT is used to localize the tumor and determine the
optimal approach. 4. Standard surgical preparation and draping are
performed. (Putnam et al., 1999).
Contraindications of RFA
• The absolute contraindication to lung RFA 1. Uncontrollable coagulopathy2. Madiastinal tumors3. Tumors adjacent to large vessels, esophagus and
trachea• . • Relative contraindications include:
1. Poor performance status2. Inability to safely access the tumor (eg, bullous
disease or central tumor location). 3. Cardiac devices such as pacemakers and
defibrillators,(Sano et al., 2007)
Complications of RFA
1. Pleurisy and small pleural effusions.2. Cough. 3. Pneumothorax.4. Acute pulmonary hemorrhage. 5. Bronchopleural fistula.6. Systemic embolization, with potential
stroke7. Skin burns8. Tumor seeding at the RFA track (Dupuy et al., 2002)
• This study was done at Mansoura university Egypt over 3 years from 2008 to 2011.
• It was planned to evaluate the safety and efficacy of radiofrequency ablation in palliative treatment of peripheral non small cell lung cancer.
The patients were divided into 2 groups:
Group A; included 10 patients who were subjected to one session of radiofrequency ablation followed by systemic chemotherapy.
Group B; included 15 patients who were subjected to systemic chemotherapy alone.
All patients were subjected to the following: Medical history: age, sex, occupation, residence, and
smoking Symptoms scoring: for cough, haemoptysis and chest
pain (before, 3 and 6 months after the start of treatment. Performance status: was done using Karnofsky
performance scale . General examination: of the patient and local
examination of the chest. Routine laboratory tests:
Complete blood picture (CBC), liver functions tests, kidney function tests, coagulation profile and ABGs.
Radiological investigations:• X-ray chest. • CT chest : The first and second CT for diagnosis
and treatment planning, third was done immediately after RFA to assess the efficacy of the procedure and to detect the early complications, fourth, fifth and sixth CT` at 1, 3 and 6 months to evaluate the radiological changes in the tumour, size and delayed complications.
• Pelvi-abdominal ultrasonography, CT of the abdomen, CT brain and bone scan for exclusion of distant metastasis).
Fiberoptic bronchoscopy.
Pulmonary function tests.
TNM staging.
• Radiofrequency Ablation:
was performed percutaneously under computed tomography fluoroscopic guidance with an array-type electrode (LeVee electrode) and radiofrequency generator (RF 3000 Boston Scientific Natick, Massachusetts, USA).
Demographic data and smoking index of the studied patients.
Demographic data and smoking index of the studied patients.
Group A)N = 10(
Group B)N =15(
Total )N =25(
n%n%n%
Sex
Male 990%1386.7%2288%
Female 110%213.3%312%
Smoking
Non smoker220%320%520%
Mild0016.7%14%
Moderate440%533.3%936%
Sever330%320%624%
Ex-smoker110%320%416%
Tumor site of the studied patients.Tumor site of the studied patients.Group A
)N = 10(Group B
)N =15(Total
)N =25(
n%n%n%
Tumor site
Left side660%426.7%1040%
lower lobe220%16.7%312%
upper lobe440%320%728%
Right side 440%1173.3%1560%
upper lobe 110%320%416%
lower lobe220%533.3%728%
middle lobe110%320%416%
Pathologic types of the tumors and age of the studied patients.
Pathologic types of the tumors and age of the studied patients.
Group A)N = 10(
Group B)N =15(
Total )N =25(
n%n%n%
Pathology
Sq c c.440%426.7%832%
Adeno c550%960%1456%
Large c c 110%213.3%312%
Mean ± SDMean ± SDP value
Tumor size6.96± 1.55547.47 ± 1.31080.380
Age58.4 ± 8.126856.5 ± 9.16410.607
Symptoms scoring and Karnofsky scale of the studied patients before the start of
treatment.
Symptoms scoring and Karnofsky scale of the studied patients before the start of
treatment.
Chest painCoughHaemoptysisKarnofsky
scale
Mean ± SDMean ± SDMean ± SDMean ± SD
Group A2.1 ± 0.48301.9 ±
0.31620.5 ± 0.707156.0 ± 13.4989
Group B1.7± 0.2791.7 ±
0.48300.5 ± 0.527052 ±8.6189
P value0.180.3280.8930.373
Comparison between cough score before, 3 and 6 months after treatment in
both groups.
Comparison between cough score before, 3 and 6 months after treatment in
both groups.
BeforeAfter 3 months
After 6
monthsP value
Mean ± SD
Mean ± SDMean ± SD0 vs 3 m0 vs 6 m
Group A1.9 ± 0.316
0.3 ± 0.4830.2 ±
0.4216 <0.001 <0.001
Group B1.7 ±
0.4830.9 ± 0.798
0.8 ± 0.8338
0.0030.003
P value0.3280.0350.029
Comparison between chest pain score before, 3 and 6 months after treatment in both
groups.
Comparison between chest pain score before, 3 and 6 months after treatment in both
groups.
BeforeAfter 3 months
After 6
monthsP value
Mean ± SDMean ± SDMean ± SD0 vs 3 m0 vs 6 m
Group A2.1 ± 0.483
0.2 ± 0.3160.1 ± 0.632 <0.001 <0.001
Group B1.7 ±
0.2791.2 ± 0.9611.2 ± 0.8840.0920.068
P value0.18< 0.0010.003
Comparison between haemoptysis score before, 3 and 6 months after
treatment in both groups.
Comparison between haemoptysis score before, 3 and 6 months after
treatment in both groups.
BeforeAfter 3 months
After 6
monthsP value
Mean ± SDMean ± SDMean ± SD0 vs 3 m0 vs 6 m
Group A0.5 ± 0.7070.1 ± 0.3160.1 ± 0.3160.1040.104
Group B0.5 ±
0.5270.4 ± 0.5160.6 ± 0.5070.5820.670
P value0.8930.0570.011
Comparison between Karnofsky scale before, 3 and 6 months after treatment in
both groups.
Comparison between Karnofsky scale before, 3 and 6 months after treatment in
both groups.
BeforeAfter 3 months
After 6
monthsP value
Mean ± SDMean ± SDMean ± SD0 vs 3 m0 vs 6 m
Group A56.0 ± 13.499
66 ± 15.776
74 ± 9.6610.015≤ 0.001
Group B52 ± 8.61957 ± 7.03755 ± 9.9040.0060.238
P value0.3730.073≤ 0.001
Symptom improvement 6 months after treatment in both groups
Tumor sizes before and 6 months after treatment in both groups, measured with
CT chest.
Tumor sizes before and 6 months after treatment in both groups, measured with
CT chest.
BeforeAfter 3 months
After 6
monthsP value
Mean ± SDMean ± SDMean ± SD0 vs 3 m0 vs 6 m
Group A6.96 ± 1.5555.774 ± 2.2265.29 ± 2.7780.0060.010
Group B7.47 ± 1.3117.323 ± 1.6097.3 ± 2.0830.6370.787
P value0.3800.0490.026
Radiological response in tumor mass after 3 months of treatment in both groups.
Radiological response in tumor mass after 3 months of treatment in both groups.
CompletePartialTotal
responseStableProgression
n%n%n%n%n%
Group A)N =
10(
00440%440%550%110%
Group B
)N = 15(
0016.7%16.7%853.3%640%
Radiological response in the tumor mass after 6 months of treatment in both
groups.
Radiological response in the tumor mass after 6 months of treatment in both
groups.
CompletePartialTotal
responseStableProgression
n%n%n%n%n%
Group A)N = 10(1
10
%330%440%440%220%
Group B )N = 15(00213.3%213.3%426.6%960%
Relation between the size of the tumors and the total response to treatment
among the studied groups.
Relation between the size of the tumors and the total response to treatment
among the studied groups.
Largest diameter ≤ 5 cmLargest diameter < 5 cm
ResponseNo responseResponseNo response
n%n%n%n%
Group A2/366.6%1/333.4%2/728.6%5/771.4%
Group B0/20%2/2100%1/137.7%12/1392.3%
Complications of radiofrequency ablation in group A.
Complications of radiofrequency ablation in group A.
FeverChest painHaemoptysisPneumothorax
n%n%n%n%
Group A)N = 10(
770%550%220%110%
Mean survival in both groups. Mean survival in both groups.
One year survival
survival (months)
P value
Mean ± SD
Group A66%17.67 ± 2.130.007
Group B54%12.83 ± 2.71
Survival Functions
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Conclusion
1.RFA is an adjuvant, effective and safe modality with minimal side effects as a palliative treatment for patients with inoperable peripherally located NSCLC.
2.Efficacy of RFA is better for smaller compared to larger tumors.
Conclusion
3. CT chest is a reliable method for assessing the precise therapeutic efficacy of RFA during follow up.
4. Combination of RFA and chemotherapy may improve the survival rate and quality of life.
Recommendations
1. Response may be better if the tumor is treated with multiple sessions of RFA.
2. To avoid the expected radiological hazards for the patients after repeated CT scans; other alternative more safe image modalities as ultrasound or MRI may be investigated for tumor localization, electrode insertion into the lung and follow up after RFA.
Recommendations
3. RFA may be used through FOB with use of long probes for palliation of endobronchial tumors.
4. RFA may be used for treatment of other intrathoraxic malignancies as pulmonary metastasis and mesothelioma as well as destruction of TB granuloma or mycetoma which are difficult and expensive to treat.