RFA is an effective alternative to lobectomy for lung cancer

Approximately 213,380 new cases of lung cancer are diagnosed annually in the United States; as a result, lung cancer continues to be the leading cause of cancer-related deaths in both men and women.1 Surgical lobar resection with systematic hilar and mediastinal lymph node dissection offers the best opportunity for cure and is the standard treatment for earlystage non-small cell lung cancer (NSCLC).2-5 Unfortunately, numerous patients with resectable early-stage disease are unable to tolerate pulmonary resection. Compromised cardiopulmonary function or medical comorbidities may make patients unsuitable candidates for the procedure.

Newer techniques can be used to treat patients who are poor candidates for lobectomy. Limited pulmonary resections such as a wedge or segmentectomy can be performed on patients who can tolerate some loss of lung function. External beam radiation therapy is used to treat patients who are a poor risk for any pulmonary resection; however, the results are inferior to resection, the cure rate is low, and the procedure carries a risk of radiation injury to surrounding tissues. In addition, radiation pneumonitis is a potentially life-threatening problem, particularly for patients with severely impaired pulmonary function. These factors have prompted the development of new treatment modalities.

Radiofrequency ablation (RFA) offers hope for patients who are considered to be poor candidates for curative resection. RFA is a minimally invasive treatment option that uses high-energy waves to create frictional heat that results in cell death and the destruction of solid tumors. The technique has been used extensively to successfully treat tumors in the liver, bone, and kidneys and is now being used to treat lung tumors. Patients with lung tumors who refuse or are unable to undergo surgical resection often can tolerate RFA therapy.

CASE

An 89-year-old man presented with a newly diagnosed adenocarcinoma in the left upper lobe. The lesion was initially seen on CT scan obtained secondary to a fall that caused a subarachnoid bleed. As a result of the fall, the patient now uses a wheelchair and resides in a skilled nursing facility. The patient came to our clinic accompanied by his son. They had already discussed treatment options with a medical oncologist who determined that chemotherapy would not be the best treatment for the patient's localized disease. However, the patient and his son were reluctant to agree to a major surgical procedure. The medical oncologist therefore referred them to our clinic for a second option.

The initial CT revealed a 232-cm nodular consolidation in the left upper lobe. The patient was treated with antibiotics to rule out pneumonia, and repeat CT showed the lesion had increased in size. Subsequent CT-guided fine-needle aspiration findings were consistent with adenocarcinoma favoring primary lung cancer. Positron emission tomography (PET) showed intense uptake in the anterior segment of the left upper lobe that measured 3.132.9 cm. No mediastinal lymphadenopathy or evidence of metastatic disease was appreciated elsewhere on the PET scan. Pulmonary function test findings were forced expiratory function 70% of predicted with a lung diffusion capacity of carbon monoxide 17% of predicted. The patient had a nonproductive cough and dyspnea. He denied hemoptysis, wheezing, fever, chills, night sweats, or weight loss.

Medical history was significant for a nephrectomy 55 years ago to treat renal cell cancer. Other significant medical history included hypertension, a cerebrovascular accident, a seizure disorder, hydrocephalus with shunt placement, previous carotid endarterectomy, benign prostatic hypertrophy, dyslipidemia, and osteoarthritis. The patient had had a significant 48-pack year smoking history but quit smoking about 40 years ago. On physical examination, the patient was in no acute distress. His speech was slightly slurred and he had residual left side hemiparesis. The trachea was midline with decreased breath sounds throughout. Accessory muscle use was not appreciated. Cardiac examination findings were regular but with trace edema in the lower extremities. Oxygen saturation was 95% on room air.

The ideal approach would have been surgical resection with curative intent; however, the surgeon determined that our patient was not a good candidate for surgery because of his age, medical history, and marginal performance status. On the other hand, he was a good candidate for RFA therapy. After some discussion, the patient and his family agreed to this recommendation.

The procedure A scout CT obtained with the patient in the supine position revealed the 3.1-cm lesion to be in the anterior segment of the left upper lobe (see Figure 1). The best site for access to the tumor was selected, and a mark was made on the patient's chest wall. The position of the mark was confirmed with repeat CT. A 22-gauge spinal needle was then inserted up to the pleura. The angle of the spinal needle was verified via repeat CT, and the needle was advanced into the tumor (see Figure 2). A multitine expandable probe was inserted tandem to the spinal needle, and repeat CT confirmed that the probe was in the center of the tumor.

The tines were sequentially deployed to 2-, 3-, and 4-cm, and the target temperature of 90ºC was reached at each deployment. After the tines were fully deployed to 4 cm, repeat CT confirmed that the tines extended beyond the edge of the tumor (see Figure 3). The tumor was ablated using standard RFA protocol (see Figure 4); ablation usually takes 12 to 22 minutes. After the ablation was completed, the tines were retracted and removed slowly to allow for tract ablation. Tract ablation is used to destroy any cancerous cells that might remain and coagulate in the probe tract. A final CT showed no evidence of pneumothorax (see Figure 5). The patient was transferred to the recovery room in stable condition. After an episode of uncontrolled hypertension on postoperative day 1, the patient was discharged on postoperative day 2.

DISCUSSION

Studies show that RFA is a safe and feasible treatment for NSCLC. RFA was initially performed using open thoracotomy under general anesthesia, which is the most controlled method. However, a thoracotomy may be contraindicated because of the patient's condition, and thoracoscopic surgery does not allow optimal needle deployment within the tumor. The most common method is a CT-guided percutaneous approach under local anesthesia. The advantage of this method is that it is minimally invasive.

RFA produces an alternating current that moves from the active electrode (the probe) within the tumor to a dispersive electrode (Bovie pad) placed on the patient (see Figure 6). As the radiofrequency energy moves from the active electrode to the dispersive electrode and back to the active electrode, ions within the tissue oscillate in an attempt to follow the direction of the alternating current;4 this causes frictional heat within the tissue. As the temperature within the tissue rises above 60ºC, protein denaturation and coagulation necrosis cause instantaneous cell death.4 Boston Scientific, AngioDynamics (formerly RITA Medical Systems), and Valleylab Systems offer devices that are FDA approved for RFA therapy of soft tissues. However, clinical studies comparing the RFA systems to determine which would produce a better result are limited. The AngioDynamics and Boston Scientific systems use an expandable multi-tine probe that produces a spherically shaped ablation. The Valleylab Ablation System device uses a cluster probe that produces a more elliptically shaped ablation. A recent study from Japan associated a higher recurrence rate with the use of a cluster probe;6 however, further studies that compare the outcomes achieved with the different RFA systems and ablation modalities are needed.

Potential complications RFA is becoming the modality of choice for minimally invasive treatment because of its lower rate of complications. The most common complication after percutaneous RFA is pneumothorax, which is reported in 30% of cases.5 Not all incidences of pneumothorax require a chest tube; and, if placed, the chest tube can usually be removed on postoperative day 1. Other less common complications are delayed pneumothorax, pneumonitis, hemorrhage, or hemoptysis. One study reported an incidence of fatal hemoptysis after RFA on a lesion in the hilar region.2 As a result, percutaneous RFA is not recommended for centrally located lesions. Risk of massive hemorrhage or hemoptysis is likely related to the proximity of the tumor to large vascular structures such as pulmonary veins, arteries, or great vessels. The length of hospital stay ranges from 1 to 7 days, with at least 1 day for cases of delayed pneumothorax; the mean length of hospital stay was 3 days.2

Patient selection Although RFA is proven to be an excellent option for the treatment of nonresectable early-stage NSCLC, there are contraindications for the procedure. RFA is not recommended for tumors located close to the hilum or any large vascular structures. Tumor proximity to a large vessel increases the risk of hemorrhage; in addition, blood flow in large vessels does not allow the temperature to reach the target level and a phenomenon known as heat sink occurs. Heat sink leads to suboptimal ablation.

Some peripheral lesions are not accessible using a percutanous approach. Overlying structures, such as the ribs or scapula, can make it difficult to place an electrode into the tumor.2 Small apical lesions or posterior-based tumors that are close to the diaphragm are also difficult to access and treat.2

RFA can be a reasonable adjunct therapy for patients with more advanced stage cancer. Patients who have responded to radiation therapy and chemotherapy but have persistent solitary peripheral tumors may benefit from RFA.4,5 RFA is also an alternative to pulmonary metastasectomy in patients who are poor candidates for surgery or in patients with recurrent lung cancer.5 In some reports, RFA was used on a centrally located tumor in conjunction with thoracotomy wedge resection of a primary tumor on the periphery to preserve lung parenchyma. RFA on a centrally located lesion is safer with a thoracotomy because the incision allows for optimal visualization of the vasculature and direct access to the tumor.4

Treatment response Unlike pulmonary resection, RFA leaves some residual mass. This is an inflammatory response; after 1 to 3 months, it becomes an atrophied nodule of coagulated necrosis within a fibrotic capsule. Determining whether the mass is scar tissue or residual cancer is difficult. A sign of effective ablation is the demonstration of central cavitations in the lesion. The timing and progression of these postablation changes become an important issue when evaluating treatment response. Current studies focus on assessing treatment response in order to standardize follow-up protocols.

Follow-up includes serial CT and PET scans to check for signs of tumor growth. At our facility, patients are followed up with alternating CT and CT/PET scans at 3-month intervals. PET scans can have false-positive uptake in the periphery of treated lesions. Therefore, CT is also obtained because it shows morphology of the lesion. We choose to alternate between the two for cost convenience to the patient.

Recent studies have found that RFA is less efficient in nodules larger than 5 cm in diameter. In our initial experience with RFA, we treated 33 tumors in 18 patients. Tumor pathologies included metastatic carcinoma (n = 8), sarcoma (n = 5), and NSCLC (n = 5). Using the modified RECIST (Response Evaluation Criteria in Solid Tumors) criteria, we found a radiographically confirmed response in 66% of tumors 5 cm or smaller, compared to 33% of tumors larger than 5 cm.7 A recent study reported the results of 19 patients with stage 1 NSCLC who were treated with RFA. The mean follow-up was 29 months. Local progression occurred in 42% of patients, and the median time to progression was 27 months. The estimated overall survival at 1 year was 95%.8 Some investigators have resected tumors after RFA ablation to evaluate the efficiency of the ablation.9,10 These studies demonstrate that RFA produces effective ablation; however, 100% cell death is not guaranteed in every case.9,10 Therefore, resection should still be the favored approach whenever possible.

CONCLUSION

Primary care providers often diagnose or locate lung lesions on routine chest radiographs and, in many cases, are included in treatment discussions with patients. For this reason, PAs in all fields should be aware of the different treatment options available. In most centers, lobectomy remains the preferential treatment for NSCLC, but now other treatment options are available for those patients who are poor candidates for resection.

RFA causes the destruction of lung tumors. The procedure is performed under local anesthesia and produces limited toxicity to adjacent tissue. RFA offers localized control of the tumor and preservation of vital, unaffected lung tissue in higher-risk patient groups. Increased risk is associated with prohibitive lung function or serious comorbid illnesses. However, in the absence of long-term data and the uncertainty of achieving a 100% tumor kill with a surrounding margin with RFA, resection should continue to be offered as the preferred treatment for NSCLC. Further studies are needed to determine the long-term prognosis and to standardize assessments of treatment response between facilities. JAAPA

Scott Cackler works for the Heart, Lung & Esophageal Surgery Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. Ghulam Abbas is director of image-guided thoracic surgery and assistant professor, the Heart, Lung & Esophageal Surgery Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. The authors have indicated no relationships to disclose relating to the content of this article.