IR IN LUNG CANCER .- Role of Interventional Radiologist in the managment of lung cancer

Interventional Radiology in Lung Cancer

1. INTERVENTIONAL RADIOLOGY IN LUNG MALIGNANCY Dr Brijesh Ray Consultant Interventional Radiologist Aster Medcity , Kochi

2. MODERN CANCER THERAPY CHEMOTHERAPY RADIATION THERAPY SURGERY

3. Interventional Radiology is emerging as a fundamental discipline involved in cancer treatment Percutaneous Ablation Embolisation Techniques Intra-arterial drug delivery

4. Headings I intent to cover Patient and nodule selection Procedure and planning Ablation energies Safety and complications of percutaneous ablation Future techniques Take home message

5. Patient and Nodule Selection Early stage patients who are good surgical candidates proceed to surgical resection What about those with multiple co-morbidities and/or poor lung function? Upto 50% of their mortality will still be Ca-related

6. H igh surgical risks- either due to underlying medical comorbidities, or due to inadequate respiratory reserve, for instance COPD or previous contralateral lobectomy or pneumonectomy making intra-operative one-lung ventilation difficult. In general, there are no lower limits of lung function requirement for ablation candidates , but patients should be expected to tolerate sedation or general anaesthesia at supine, lateral decubitus or semi-prone position for at least an hour. Contraindications for ablation include severe ILD

7. Solitary lesions (usually) 3 cm or less Non-small cell histology Location Safe reasonable percutaneous route No extension to hilum/mediastinum Not contiguous with major vessels or nerves Ablation with palliative intent is best suited for lung cancers with tumor -related symptoms, for example pain and airway obstruction. increased risk of local recurrence for increasing size of tumors , with cut-off of 2 cm and 3 cm reported. DupuyDE , FernandoHC , HillmanS , et al. Radiofrequency ablation of stage IA non-small cell lung cancer in medically inoperable patients: Results from the American College of Surgeons Oncology Group Z4033 (Alliance) trial. Cancer 2015; 121(19): 3491-3498. DOI: 10.1002/cncr.29507. larger tumors - double ablation may be required . 

8. Tumor Location- not suitable candidates for CT-guided biopsy are generally not recommended for percutaneous ablation Tumors located close to medium to large blood vessels are susceptible to heat-sink effects tumors close to the apex or mediastinal structures - thermal injury to brachial plexus, phrenic nerve and adjacent organs such as the heart and esophagus

9. Procedure and Planning Pre procedure work up: CT/PET CT imaging ideally within 4 weeks GA/sedation Pacemaker or defibrillator- should be ideally turned off-probes should be placed atleast 5cm from the leads Grounding pads for RF

10. The aim of all ablation modalities is to create a zone of tissue necrosis that encompasses both the tumor and a margin of normal parenchyma surrounding it. The choice of electrode length, active tip length and the number of electrodes is determined by the size and location of tumor . The actual ablation zone size may differ from the predicted size. Factors include the heat-sink effect , - medium to large blood vessels or airways carry heat away leading to asymmetrical or truncated ablation zones. Depending on the energy used, the lung’s conductivity, impedance and density also play a role in affecting the eventual ablation zone volume.

11. Post Ablation Check CT Observed for 4hrs PACU Repeat Chest Xray after 4hrs Discharge next day

12. I nterval CT scans for evaluation of treatment response, usually every 3 months although no international guideline exists . Typical early CT appearances following ablation - include ground glass opacities or cavities, with or without soft tissue components. GGO - typically concentric with three layers central consolidation - ablated tumor tissue middle layer of faint GGO - necrotic surrounding parenchyma an outer rim of denser GGO - congested lung tissue and hemorrhage

13. Signs of recurrence Enlarging ablation zone beyond 6 months Central enhancement >10 mm or > 15HU suggests progression increased metabolic activity or new uptake inside the ablation zone beyond 2 months post-ablation

14. Ablation Energies Thermal based tumour ablation system Mechanism of action: Thermal energy- damage to cellular proteins, enzymes, nucleic acids. Creates a volume of tissue necrosis coagulation

15. RADIOFREQUENCY ABLATION MICROWAVE ABLATION CRYOABLATION IRREVERSIBLE ELECTROPORATION

16. RFA Most widely used - utilizes heat as a form of thermal ablation. A grounding pad or reference electrode is required in RFA, while the active electrode placed inside the tumor is coupled to an RF generator. RF generator establishes a voltage between the active electrode and reference electrode, producing electric field lines that oscillate with alternating current. At the area closest to the applicator, electrons collide with adjacent molecules under the influence of oscillating electric field, inducing frictional heating . Immediate cell death occurs at temperatures greater than 60°C. Treatments usually range between 4 and 12 minutes RFA electrodes may be single-tip applicators or cluster electrodes.

17. Efficacy of RF ablation RAPTURE TRIAL- 2009 - m ulticenter trial involving seven centres in Europe, USA and Australia . 106 patients with 183 biopsy-proven lung tumours. Technical success rate was 99%, and a confirmed complete response lasting at least 1 year was achieved in 88% of patients. overall survival was 70% at 1 year and 48% at 2 years, cancer-specific survival was 92% at 1 year and 73% at 2 years ALLIANCE TRIAL - 2015-multicentre trial - overall survival was 86.3% at one year and 69.8% at two years, while local recurrence-free rate was 68.9% at one year and 59.8% at two years . Long term efficacy - complete response rate was 59.3% at a mean follow-up of 47 months, with a mean local recurrence interval of 25.9 months . Median overall survival and cancer-specific survival were 33.4 and 41.4 months respectively, while cancer-specific actuarial survival was 59% at 3 years and 40% at 5 years 

18. Tumor diameter was found to be a negative prognostic factor. The difference between survival curves associated with large (>3 cm) and small (<=3 cm) lung tumors was significant (p = 0.002, 10] and there was a trend toward better efficacy for tumors smaller than 2 cm in diameter (p = 0.066, 23]. Tumor size less than 2 cm was associated with a statistically significant improved survival of 83% at two years in the ALLIANCE Trial 

19. RFA Well tolerated, no incision Reliance on post-ablation imaging No assessment of nodes SURGICAL RESECTION Higher patient impact Pathology available for margins Nodal status determined

20. Sub-lobar resection, RFA, cryoablation compared Overall 3-year survival 87% (SLR), 87 %(RFA), 77 %( cryo ) 3-year disease free survival 61% (SLR), 50% (RFA), 47 %( cryo ) No significant difference between the 3 groups Zemlyak et al., J Am Coll Surg , 2010

21. RFA Local therapy with less collateral damage Single session, but repeatable Potential for procedural complication SBRT Effects on adjacent lung tissue dosage limitations Multiple visits Fewer complications

22. Radiation therapy (conventional EB) vs Surgical resection (LR, sub LR, VATS) No difference in DFS ABLATION? OS at 5 years 15-30 OS at 5 years 40-55 SBRT Better at local dz control OS _at_ 5 yrs 50 Overall survival data in RFA series tends to reflect a population with more co-morbidities, but Ca specific survival is encouraging

23. MWA frequency range in the electromagnetic spectrum between 300 MHz to 300 GHz Much larger zone of active heating due to broader deposition of energy Directly heats tissue to lethal temperatures greater than 150°C through dielectric hysteresis- a process in which the polar water molecules realign with the oscillating electric field generating kinetic energy, which is then transferred to neighbouring tissues aerated lung has a relatively high impedance among all solid organs, thus making MWA a better modality than RFA in lungs Less heat sink effect CRYOABLATION Joule-Thomson effect by distributing pressured argon gas to an area of lower pressure and reaching ultracold temperatures when the gas expands  -140degrees protein denaturation, cell rupture due to osmotic shifts, and tissue ischemia from microvascular thrombosis  larger ablation volumes multiple applicators highly visible ablation zone  less pain due to analgesic effect of freezing safety near vasculature or bronchi due to the ability to preserve collagenous tissue and cellular architecture in frozen tissue

24. MW - actuarial survival of 65% at 1 year, 55% at 2 years and 45% at 3 years, while cancer-specific survival was 83%, 73% and 61% at 1, 2 and 3 years respectively Local control rate was 84.4% at a mean follow-up of 446 days in another retrospective series  A larger retrospective review of 108 patients reported that the median time to tumor recurrence was 62 months, and recurrence rates were 22%, 36% and 44% at 1, 2 and 3 years respectively Recurrence rate was 17% for tumors smaller than 3 cm, and increased to 31% for those greater than 3 cm 

25. In a best evidence topic review, the best available evidence for MWA (7 studies) was compared to that for SBRT (5 studies) . The 3-year survival was 29.2–84.7% for MWA and 42.7–63.5% for SBRT, while the median survival was 35–60 months for MWA and 32.6–48 months for SBRT. The authors concluded that MWA appears comparable to SBRT in terms of local control and survival rates. WatsonRA , TolI , GunawardanaS , TsakokMT . Is microwave ablation an alternative to stereotactic ablative body radiotherapy in patients with inoperable early-stage primary lung cancer? Interactive Cardiovascular and Thoracic Surgery 2019; 29(4): 539-543. DOI: 10.1093/ icvts /ivz123.

26. COMPLICATIONS PNEUMOTHORAX- 3.5 -54% (10% delayed ) - 6-15% require ICD PLEURAL EFFUSION/ASEPTIC PLEURITIS BLEEDING/HEMOTHORAX – 1.6-18% - rarely for embolization PNEUMONIA,BRONCHOPLEURAL FISTULA, LUNG ABSCESS PNEUMONITIS

27. OUR CENTRE EXPERIENCE 9 cases from 2017-2022 MDT – Pulmonologist, Thoracic surgeon, IR, Rad Onco , Med Onco , NM Median age 80 8 solitary tumors and 1 case with 2 lesions Comorbidities- Age, CAD, DM ,CLD, Post LDLT NSCLC- Stage I/II </=3 cm Did hydro dissection in 2 cases No major complications Followed up with PET CT- 2 cases of recurrence ( both of them just above 3 cm tumors)- did SBRT

28. CASE 1

29. CASE 2

30. FUTURE TPCE/TACE BAI Regional Chemotherapy of the Lung: Transpulmonary Chemoembolization in Malignant Lung Tumors Thomas J. Vogl , MD1 Mohammad Shafinaderi , MD1 Stefan Zangos , MD1 Sebastian Lindemayr , MD1 Khashayar Vatankhah , MD1 1 Institute for Diagnostic and Interventional Radiology, Johann Wolfgang Goethe University Hospital, Frankfurt am Main, Germany

31. TAKE HOME MESSAGE Ablation can be used to treat both primary/ metastatic tumors Doesn't preclude other complimentary therapies Patient selection is key/critical (not about the speciality, ego, or absolutes- its about the PATIENT)

32. THANK YOU FOR YOUR ATTENTION