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Thermal ablation for pulmonary subsolid nodules: Which consensus guidelines? which future perspectives?

 Fondazione Policlinico Universitario A. Gemelli IRCCS, Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia – Istituto di Radiologia, l.go A gemelli 8, 00168; Università Cattolica del Sacro Cuore, ROMA, Italia

Date of Submission20-Dec-2021
Date of Acceptance25-Dec-2021
Date of Web Publication25-Feb-2022

Correspondence Address:
Roberto Iezzi,
Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli - IRCCS, Università Cattolica del Sacro Cuore, L.go F.Vito 1, Zip code: 00168, Rome
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcrt.jcrt_283_22

How to cite this URL:
Iezzi R. Thermal ablation for pulmonary subsolid nodules: Which consensus guidelines? which future perspectives?. J Can Res Ther [Epub ahead of print] [cited 2022 Dec 8]. Available from: https://www.cancerjournal.net/preprintarticle.asp?id=338429

Lung cancer is the second most common cancer and the leading cause of cancer death worldwide among both men and women, making up almost 25% of all cancer deaths.

The increasingly widespread use of computed tomography (CT), high-resolution CT imaging, lung cancer screening programs, and surgical advancements allowed to obtain a significant reduction of lung cancer mortality, up to 20% in the high-risk population, even if it also leads to increased detection of asymptomatic pulmonary nodules, most of them benign, with a cancer detection rate of only 0.7–2.3%. In particular, an estimated incidentally ground-glass nodules (GGNs) or ground-glass opacities (GGOs) detection frequency of 8.72–27.3% on CT was found, many of which are multiple pulmonary nodules.[1],[2]

The high rate of false-positive results, which represented 24% of all screens and 95% of all positive screens, may lead to overdiagnosis, overtreatment, waste of medical resources, and higher levels of anxiety in patients. Furthermore, it could also lead to a premature surgical intervention with early and potentially unnecessary organ damage and lung function loss without significantly improving the overall survival of patients.[3]

Based on this background, it seems very interesting, up-to-date, and useful not only for residents and fellows who are training in interventional radiology but also for practicing colleagues who are approaching this locoregional treatment, the published 2021 Multidisciplinary Expert Consensus (provided by the Expert Group on Tumor Ablation Therapy of the Chinese Medical Doctors Association, the Tumor Ablation Committee of the Chinese College of Interventionalists, the Society of Tumor Ablation Therapy of the Chinese Anti-Cancer Association, and the Ablation Expert Committee of the Chinese Society of Clinical Oncology).[4] The multidisciplinary panel of experts provided a clear clinical evaluation of GGN, highlighting treatment management, with treatment indications as well as contraindications and potential post-procedural complications and outcomes, focusing on the emerging role of percutaneous thermal ablation as an alternative to surgery.

The management for GGNs is different and controversial, needing a thoughtful discussion evaluating different issues, with some particular conditions that could highlight and justify conclusions of the authors on the potential future role of thermal ablation for GGN, challenging surgery, and becoming its novel therapy.

High-risk Surgical Patients: Firstly, despite surgical advancements, represented by the use of video-assisted thoracoscopic surgery (VATS) and single-portal wedge resections, percutaneous ablation could represent an alternative mini-invasive treatment option for patients at high surgical risk because of their poor cardiopulmonary function, advanced age, or other medical comorbidities or patients who refused surgery.[5],[6]

Issues of Tumor Biology: Surgical resection is still currently considered the gold standard for the treatment of stage 1 NSCLC, as also reported in the meta-analysis of Chan et al.,[7] with a significantly better 1- and 2-year DFS compared with ablation, even if without significant difference in terms of 1- to 5-year OS, and 3- to 5-year DFS between ablation and surgery. It is well known that one advantage of surgery over ablation is lymph node sampling or dissection that allows for the identification and treatment of unsuspected nodal disease and, therefore, more precise staging compared to ablation, being the prognosis of lung cancer mainly affected by hilar and mediastinal lymphatic metastases and distant metastases. However, GGNs are characterized by “indolent” development, with distant metastasis in very few patients. In detail, a retrospective analysis revealed that GGNs with a consolidation/tumor ratio (CTR) < 0.5 had no metastasis to the pulmonary hilus or mediastinal lymph node, 10% of GGNs with CTR > 0.5 had metastasis, and AAH, AIS, MIA, and lepidic-dominant adenocarcinomas and invasive mucinous adenocarcinoma had no lymph node metastasis.[8] These conclusions provided a theoretical foundation for the treatment of pGGN and even mGGN (CTR < 0.5) by thermal tumor ablation, through its thermo biological effects, also achieving curative ablation, leading to complete necrosis of lung tumor and local control not change in high-risk surgical patients.

Number of GGNs: The NELSON study (3392 participants; 7258 nodules) showed that nearly half of the participants had multiple pulmonary GGNs.[9] These nodules should be treated as multiple primary lung cancers with complete surgical resection, as long as it is feasible to remove all lesions. However, complete resection for all lesions is difficult for patients with poor cardiopulmonary function, prior pulmonary resection, or those with numerous lesions. Thermal ablation, also combined with surgery in a hybrid approach, could represent an adequate alternative for those who cannot tolerate or who refuse a second surgery for new or remaining lesions after their surgical resections.

Technical Aspects – New Ablative Techniques: In the last decade, there has been an increasing shift toward the use of microwave ablation (MWA) instead of Radiofrequency ablation( RFA). The main benefits of MWA in comparison to RFA lung tumor ablation include larger ablation zones, shorter healing time, higher intralesional temperatures, less procedural pain, and less susceptibility to both insulating effects intrinsic to lung tissue and those associated with tissue charring. The meta-analysis of Chan et al.[7] found higher pooled overall survival (OS) rates for MWA compared to RFA (1y: 99% vs 92%, 5ys: 50% vs 15%). Furthermore, in a study that compared MWA with surgery, there were no significant differences in OS or DFS between MWA and lobectomy.[10]

In the published study of Huang and his colleagues,[11] including 33 patients with 103 pulmonary GGOs treated in 66 MWA sessions, a three-year local progression-free survival (PFS) and OS of 100% were registered, with encouraging results. Our recent multicenter published paper also demonstrated the possibility to overcome one of the recognized main limitations of MWA, represented by the low reproducibility of the ablation zones. In detail, the prospective multicenter Microwave Ablation of Lung Tumors (MALT) trial confirmed that percutaneous MWA treatment of lung tumors using a 2450-MHz ablation system is repeatable, safe, and reproducible, with effective therapeutic options and optimal local tumor control for tumors up to 4 cm, covering all GGOs lesion sizes.[12]

Based on these issues, it seems clear that MWA represents an adequate alternative treatment for GGNs, in particular for multiple lesions. The peculiarity of this subtype of lung cancer highlights the crucial role of multidisciplinary tumor board consensus to obtain a personalized and tailored treatment, with great flexibility in the decision-making process based on professional background and hospital practice experience, expertise, and guidelines, lacking clear scientific evidence. To definitely become the first-line therapy for GGNs, a prospective, multicenter, randomized, and controlled study focusing on the effectiveness of MWA for single as well as multiple pulmonary subsolid nodules is needed.

In the near future, we believe that thermal ablation will definitely become a novel therapy to treat pulmonary subsolid nodules.

 > References Top

Pinsky PF. Lung cancer screening with low-dose CT: A world-wide view. Transl Lung Cancer Res 2018;7:234-42.  Back to cited text no. 1
Liu B, Ye X. Management of pulmonary multifocal ground-glass nodules: How many options do we have? J Cancer Res Ther 2020;16:199-202.  Back to cited text no. 2
Kaaks R, Delorme S. Lung cancer screening by low-dose computed tomography-part 1: Expected benefits, possible harms, and criteria for eligibility and population targeting. Rofo 2021;193:527-36.  Back to cited text no. 3
Ye X, Fan W, Wang Z, Wang J, Wang H, Wang J, et al. Expert consensus on thermal ablation therapy of pulmonary subsolid nodules (2021 Edition). J Cancer Res Ther 2021;17:1141-56.  Back to cited text no. 4
Alzubaidi SJ, Liou H, Saini G, Segaran N, Scott Kriegshauser J, Naidu SG, et al. Percutaneous image-guided ablation of lung tumors. J Clin Med 2021;10:5783. doi: 10.3390/jcm10245783.  Back to cited text no. 5
Xue G, Li Z, Wang G, Wei Z, Ye X. Computed tomography-guided percutaneous microwave ablation for pulmonary multiple ground-glass opacities. J Cancer Res Ther 2021;17:811-3.  Back to cited text no. 6
Chan MV, Huo YR, Cao C, Ridley L. Survival outcomes for surgical resection versus CT-guided percutaneous ablation for stage I non-small cell lung cancer (NSCLC): A systematic review and meta-analysis. Eur Radiol 2021;31:5421-33.  Back to cited text no. 7
Xi J, Yin J, Liang J, Zhan C, Jiang W, Lin Z, et al. Prognostic impact of radiological consolidation tumor ratio in clinical stage I. A pulmonary ground glass opacities. Front Oncol 2021;11:616149. doi: 10.3389/fonc. 2021.616149.  Back to cited text no. 8
Heuvelmans MA, Walter JE, Peters RB, Bock GH, Yousaf-Khan U, Aalst CMV, et al. Relationship between nodule count and lung cancer probability in baseline CT lung cancer screening: The NELSON study. Lung Cancer 2017;113:45-50.  Back to cited text no. 9
Wang Y, Liu B, Cao P, Wang W, Wang W, Chang H, et al. Comparison between computed tomography-guided percutaneous microwave ablation and thoracoscopic lobectomy for stage I non-small cell lung cancer. Thorac Cancer 2018;9:1376-82.  Back to cited text no. 10
Huang G, Yang X, Li W, Wang J, Han X, Wei Z, et al. A feasibility and safety study of computed tomography-guided percutaneous microwave ablation: A novel therapy for multiple synchronous ground-glass opacities of the lung. Int J Hyperthermia 2020;37:414-22.  Back to cited text no. 11
Iezzi R, Cioni R, Basile D, Tosoratti N, Posa A, Busso M, et al. Standardizing percutaneous microwave ablation in the treatment of lung tumors: A prospective multicenter trial (MALT study). Eur Radiol 2021;31:2173-82.  Back to cited text no. 12


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