RFA of Tumors of the Lung: How and Why Radiofrequency Ablation of Lung Ernest Scalzetti MD SUNY Upstate Medical University Syracuse NY FDA WARNING: Off-label use of a medical device Radiofrequency Ablation Heat-ablation of malignancy in a single session A recent development for tx of lung tumors First clinical i l experience: Dupuy, AJR 2000 Supported by successful trials in animals Our first case: 2/28/2000 Potentially curative in NSCLC >5 yr survival of patients with RFA alone: Simon, 2007 Our experience confirms this observation 25% 5-year overall survival with mature follow-up: Radiofrequency Ablation RFA of pulmonary metastases Goal of tx of lung cancer: cure or palliation. Curative intent: Pi Primary lung cancer must be solitary (e.g. stage I), or have limited, potentially controllable metastases. Pulmonary metastases Palliation: control of symptoms Pain caused by chest wall invasion Hypertrophic pulmonary osteoarthropathy Metastatic disease depends on the primary: Sarcoma Epithelial neoplasms, <4 pulmonary lesions Carcinoma Melanoma Germ Cell Tumors Favorable prognostic factors: Longer disease-free interval Fewer pulmonary metastases 1
RFA of pulmonary metastases RFA of pulmonary metastases Test of time paradigm Some patients who have lung resection for oligometastatic t ti disease re-present shortly thereafter with many more metastases. If RFA is used instead, QOL may be better and patients have a test of time to see whether additional metastases develop. Surgery would remain an option for patients with unsuccessful ablations. Reference: Livraghi T, et al. Percutaneous RFA of liver metastases t in potential ti candidates for resection: the test of time approach. Cancer 2003; 97: 3027-3035. Radiofrequency Ablation RFA Patient Selection, part 1 No evidence demonstrates superiority of RFA over other established modalities of local control: Surgical resection Radiation therapy The clinical experience with RFA is more limited Therefore it would be unethical to advise a patient to undergo RFA unless the patient is not a candidate for either of the other treatment modalities, or has been offered them and refused. Dx of malignancy must be established?ct-guided needle bx and RFA one sitting Tumor size must be suitable for RFA Up to 4 cm Best results <3 cm Local vascular anatomy Risk of bleeding Heat sink phenomenon RFA Patient Selection, part 2 RFA Patient Selection, part 3 Contraindications: Coagulopathy Multifocal disease such as BACC Pacemakers and ICDs Arrangements should be made with the cardiologist to prepare the device before RFA and return it to its pre-existing mode after RFA Notes: Prior pneumonectomy is not necessarily a contraindication ti to RFA in the remaining i lung Tumor location close to the heart does not make cardiac dysrhythmia more likely during RFA RFA may be considered for salvage if NSCLC recurs locally after XRT 2
Consultation Visit RFA Procedure, Part 1 Outpatient procedure Single session Does not preclude additional RFA treatments t t if they become necessary Will not interfere with chemotherapy or radiation therapy if the clinical circumstances warrant Moderate sedation or general anesthesia Patient arrives in outpatient unit Antibiotic prophylaxis? Controversial Consent RFA Chest tube placement Sedation or GA RFA Procedure, Part 2 LeVeen Needle-Electrode Phase I: Electrode placement Approach similar to CT-guided needle biopsy Grounding pads Accurate positioning of needle-electrode Confirmation in 3 dimensions Sample Case Medically inoperable NSCLC Pre-procedure CT image Oblique reformatted image after deployment of an expandable multitined needle-electrode, in the plane of the needle shaft. Oblique reformatted image perpendicular to the plane of the needle shaft, showing the tumor enclosed within the expected treatment volume (circle). 3
RFA Procedure, Part 3 Sample Case Phase II: Ablation process Power deposition Protocol ldepends d on manufacturer Monitoring Tissue impedence Temperature Maintainence of sedation Medically inoperable NSCLC CT image showing deployment of the needle- electrode. Immediate post-procedure CT image showing ground-glass opacity surrounding the tumor, indicative of thermal injury to the adjacent lung. 4
Complications ~ Needle Bx Complications Unique to RFA Pneumothorax: Common, reported incidence of 9-63% Air leaks may be prolonged Infection in the lung or pleural space Pulmonary hemorrhage, can be fatal Systemic air embolization, also potentially fatal Tumor seeding of the needle tract is rare Cutaneous burns Thermal injury of adjacent normal tissues Phrenic nerve injury Cerebral microembolization Rarely associated with clinical findings For several days after RFA, patients may have a mild flu-like syndrome attributed to tumor lysis Likelihood proportional to tumor volume Procedural mortality rate of <1% Sample Case Metastatic NSCLC S/p right pneumonectomy 2 years earlier 2 metastases were discovered in the LLL Ablation of the larger, more laterally-located LLL lesion, 01-21-03 5
Case, continued The patient required chest tube drainage for PTX. He returned two days later for RFA of the second LLL lesion Chest tubes still in place, but no air leak. Note appearance of the site of previous ablation. Note that there is risk of injury to diaphragm. 6
Case, continued The following week the patient returned for evaluation of PE, because of hypoxemia. Note that both RFA sites are cavitary. Small fluid collection adjacent to the left crus of the diaphragm, likely the result of thermal injury. Post-RFA Imaging Follow-Up Treatment site monitored to assess response Even when target lesion is coagulated completely, imaging features evolve for one year or more Contrast-enhanced CT At 3, 6 and 12 months after RFA, then annually 3 months: treatment site enlarges, may be cavitary No more than a thin rim of contrast enhancement Thereafter, slow contraction indicating fibrosis 7
Sample Case Medically-inoperable NSCLC Diagnostic CT image showing a small tumor, subsequently shown by needle biopsy to be a NSCLC, in the periphery of the right upper lobe. 3 month follow-up CT; the lesion has increased in size, as expected. 3 month follow-up CT, soft tissue window; there is no contrast enhancement. 9 month follow-up CT. The residual opacity at the treatment site is diminishing in size. Post-RFA Imaging Follow-Up PET with FDG Shows uptake early after therapy, <2 months Reactive changes in the lung around the treatment site Degree of uptake should decline subsequently Reported to predict tumor recurrence at 2 months after RFA SUV > 1.8 at the treatment site, or SUV that decreased less than 60% relative to pre-tx baseline Another study of FDG-PET and contrast-enhanced CT in f/u Abolition of FDG uptake was both 100% sensitive and specific for complete response, at both 1 month and 3 months after RFA Dx performance of CT was indistinguishable from PET at 3 months 8
Post-RFA Imaging Follow-Up Any unexpected CT or PET findings Needle biopsy Potential for retreatment of incompletely ablated tumors Risk of a second primary lung cancer In general, risk is ~ 2% per year in survivors of NSCLC In our series, 4/9 patients who survived more than 2 years after RFA developed a new primary lung cancer Most of these can be treated with RFA Sample Case Recurrent disease after RFA Pre-procedure CT image. Transverse CT image showing electrode placement. Oblique CT image of electrode. 3 month follow-up CT demonstrating no contrast enhancement. 12 month follow-up CT: definite tumor regrowth and new pleural disease, both of which showed uptake on FDG PET. 9
Sample Case Development of new primary lung cancer. Original NSCLC, in RLL, prior to RFA. CT image of electrode placement. CT image of electrode placement. Immediate post-procedure CT image. Diagnostic CT of treatment site at 30 months showing stable scar. No PET uptake at this site. On the same scan, a new mass was found in the upper lobe of the right lung (arrow). Scarring also is visible posteriorly at the site of a previous wedge resection. 10
Efficacy of RFA Two studies: RFA followed by resection of the treated tumor ( ablate and resect ) Permits assessment of extent of RFA-induced id d tumor necrosis One study complete necrosis in 6/9 cases In the other complete absence of viable tumor cells was observed in only 3/10 lesions Complete ablation more likely if tumor <3cm Efficacy of RFA Sample Case Little long-term follow-up data re RFA for NSCLC A series of 36 patients showed median survival of 29 months in a medically-inoperable inoperable population This compares favorably to XRT in a similar population: 3-year overall survival ~ 40% Both treatment modalities are evolving Medically inoperable NSCLC Pre-procedure CT image Immediate post-procedure CT image Post-procedure image at 5 years; residual lesion had been stable with no evidence of recurrence 11
RFA and the FDA FDA has not approved RFA for tx of lung cancers Lack of demonstrated efficacy Reported deaths Manufacturers cannot legally promote the use of their RFA devices for this indication Several centers now have >5 years of experience with RFA for NSCLC Multicenter study of RFA in clinical stage I NSCLC ACOSOG protocol Z4033, now underway Future Developments Where does RFA fits into the management of patients who suffer from lung cancer? Competitor to XRT/SBRT? Complementary treatment modality? For tumors that are likely to recur locally after XRT alone, the two modalities can be combined RFA in cases of local failure of XRT, if restaging demonstrates no other sites of disease (salvage tx) Need for clinical trials 12
Sample Images Case 1: LUL scar carcinoma (adenocarcinoma) Not a surgical candidate for medical reasons. Not a candidate for XRT previous radiation for sq. cell ca. of neck This patient is our longest survivor Treated 7/00; still alive and well 13
Radiofrequency ablation of lung masses Case 2: NSCLC The patient was not a surgical candidate because of marginal pulmonary function 14
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