Safety and efficacy of thermal ablation for small cell lung cancer liver metastases
Shunn Theingi
, Ashara Mitchell, Elena N. Petre, Etay Ziv
, Constantinos T. Sofocleous
, Stephen B. Solomon, Erica S. Alexander
Abstract: Small cell lung cancer (SCLC) is a high-grade neuroendocrine carcinoma associated with early development of distant metastases, which portends a worse prognosis. The median survival of metastatic SCLC with standard treatment is only 9–11 months, with a 5-year survival of 1–2%. Patients with SCLC are often initially responsive to systemic therapies, but once they develop resistance to them, locoregional therapies like thermal ablation should be investigated for possible improvements in morbidity and mortality. This brief retrospective report evaluates six patients with SCLC liver metastases (LMs), treated in 11 thermal ablation sessions (radiofrequency ablation or microwave ablation). Technical success was achieved in all treatments (100%). After the first ablation, 3/7 ablated tumors had residual disease. Survival outcomes were determined using the Kaplan-Meier method. Median local tumor progression-free survival (LTPFS) was 2.9 [95% confidence interval (CI): 0.5–3.9] months. Median assisted LTPFS, defined as tumor control with subsequent retreatment, was 25.9 (95% CI: 8.3–not reported) months. Median overall survival (OS) was 14.3 months. There was one adverse event (1/11) of grade 1, according to the Common Terminology Criteria for Adverse Events version 5.0, fatigue within a month of ablation, which self-resolved. The results suggest that thermal ablation is safe for SCLC LMs. Although LTPFS was very modest, the long duration of assisted LTPFS and OS in this small, retrospective study suggests that thermal ablation may be a promising treatment option.
Keywords: Thermal ablation; liver metastases (LMs); small cell lung cancer (SCLC); radiofrequency ablation (RFA); microwave ablation (MWA)
Submitted Jan 29, 2025. Accepted for publication Apr 09, 2025. Published online Jun 19, 2025.
doi: 10.21037/tlcr-2025-112
Introduction
Small cell lung cancer (SCLC) is a high-grade neuroendocrine carcinoma with a high proliferation rate, early development of widespread metastases, and a 5-year mortality exceeding 90% (1).
Patients are classified as having limited stage (LS-SCLC) or extensive stage SCLC (ES-SCLC). Per the 2010 American Joint Committee on Cancer classification system, LS-SCLC refers to T1-3N0-3M0, and ES-SCLC corresponds to patients with metastatic disease (1). While initially responsive to chemotherapy, SCLC commonly relapses within months. The median survival of patients with ES-SCLC with treatment is only 9–11 months, with a five-year survival of 1–2% (2). The presence of SCLC liver metastases (LMs) is a negative predictor of survival (3).
Thermal ablation, including radiofrequency ablation (RFA) and microwave ablation (MWA) are established treatments for primary and metastatic hepatic tumors (4). However, ablation for SCLC LMs remains understudied. The purpose of this study is to evaluate the safety and efficacy of thermal ablation in the treatment of SCLC LMs. We present this article in accordance with the STROBE reporting checklist (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-112/rc).
Materials and methods
Study population
This single-center, institutional review board-approved, retrospective study was Health Insurance Portability and Accountability Act-compliant and included all patients with pathology-proven SCLC LMs treated with thermal ablation (RFA and MWA). The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Ethics Committee of Memorial Sloan Kettering Cancer Center (No. 16-402) and individual consent for this retrospective analysis was waived. Patient selection was made in consultation between medical oncology and interventional radiology. Metastases were deemed amenable to thermal ablation after consideration of proximity to critical structures and tumor size, and if patients had an international normalized ratio ≤1.5. The intent of treatment was disease control of progressing LMs.
From May 2007 to November 2022, six patients underwent thermal ablation of 7 SCLC metastases in 11 sessions (6 RFA, 5 MWA). Details about patient and tumor characteristics are in Table 1. Each session targeted one tumor. In the RFA group, one patient had a repeat ablation for local tumor progression (LTP) and the other patient had two additional ablations for the same tumor due to LTP. In the MWA group, one patient had a repeat ablation to treat residual tumor.
Table 1
| Characteristics | RFA group | MWA group |
|---|---|---|
| Sex (female), n/N (%) | 0/2 (0%) | 2/4 (50%) |
| Age (≥60 years), n/N (%) | 1/2 (50%) | 4/4 (100%) |
| Prior lines of therapy (≥2), n/N (%) | 2/2 (100%) | 2/4 (50%) |
| Hepatic metastases at time of ablation (>1), n/N (%) | 1/2 (50%) | 2/4 (50%) |
| Tumor size (cm), largest axial dimension, median (range) | 2.35 (1.4–5.5) | 2.9 (1.8–4.2) |
| Sub-capsular location of treated tumor, n/N (%) | 4/6 (67%) | 3/5 (60%) |
| Border adjacent to ≥3 mm vascular structure, n/N (%) | 3/6 (50%) | 0/5 (0%) |
| Bilobar disease, n/N (%) | 0/6 (0%) | 1/5 (20%) |
| % liver involvement (<50%), n/N (%) | 6/6 (100%) | 5/5 (100%) |
MWA, microwave ablation; RFA, radiofrequency ablation.
Ablation procedure and follow-up
Patients were treated with commercially available radiofrequency and microwave systems, as detailed in Table 2. Treatments were performed according to manufacturer guidelines and operator preference. Computed tomography (CT) with real-time CT-fluoroscopy capabilities ± ultrasonography was used for real-time guidance, needle positioning, and monitoring of the ablation zone.
Table 2
| Patient | Session | Age at time of ablation (years) | Gender | Tumor | Size of index lesion (cm) | Sub-capsular1 | Operator experience (years post fellowship) | Ablation type | Ablation probe & manufacturer |
Number of probes | Number of activations | Ablation time (mins) | Maximum temperature (℃) | Maximum wattage (watts) | Prior treatments | Current systemic treatment |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A | I | 59 | Male | 1 | 1.6 | Yes | 12 | RFA | Cool-tip RF Ablation System2 | 2 | 4 | NA | NA | NA | Chemotherapy | None |
| II | 1* | 1.4 | No | 12 | RFA | Cool-tip RF Ablation System2 | 1 | 2 | NA | 80 | NA | Chemotherapy, RFA | None | |||
| III | 2 | 2.1 | No | 12 | RFA | Cool-tip RF Ablation System2 | 1 | 2 | NA | 80 | NA | Chemotherapy, RFA | None | |||
| B | I | 74 | Male | 1 | 4.4 | Yes | 4 | RFA | RITA XL/XLI3 | 1 | 2 | NA | NA | NA | Chemotherapy | None |
| II | 74 | 1* | 2.6 | Yes | 4 | RFA | RITA XL/XLI3 | 1 | 1 | 9 | NA | NA | Chemotherapy, RFA | None | ||
| III | 76 | 1* | 5.5 | Yes | 4 | RFA | RITA XL/XLI3 | 3 | 2 | 32 | 70+ | NA | Chemotherapy, RFA ×2 | None | ||
| C | I | 60 | Female | 1 | 4.2 | Yes | 2 | MWA | Emprint2 | 1 | 1 | 10 | NA | 150 | Chemotherapy, immunotherapy, targeted therapy | Osimertinib, docetaxel/ramucirumab |
| D | I | 70 | Male | 1 | 2.5 | No | 13 | MWA | Neuwave4 | 1 | 2 | NA | NA | NA | Chemotherapy | None |
| II | 1* | 4 | Yes | 13 | MWA | Emprint2 | 3 | 1 | 8.5 | 95 | NA | Chemotherapy, MWA | None | |||
| E | I | 78 | Male | 1 | 1.8 | Yes | 4 | MWA | Neuwave4 | 1 | 2 | 15 | NA | 40 | Chemotherapy, possible immunotherapy5 | None |
| F | I | 70 | Female | 1 | 2.9 | No | 2 | MWA | Neuwave4 | 2 | 1 | 5 | NA | 65 | Chemotherapy, immunotherapy | Irinotecan |
*Denotes retreatment of same tumor. 1Tumors were classified as subcapsular if they were <5 mm from liver edge. 2Medtronic, Minneapolis, MN. 3Angiodynamics, Latham, NY. 4NeuWave Medical, Madison, WI. 5Denotes participation in experimental research with blinding of immunotherapy. MWA, microwave ablation; NA, not available; RFA, radiofrequency ablation.
After treatment, cross-sectional imaging was obtained at 1-month and at 3-month intervals. Examples of imaging are presented in Figure 1A-1D.
Data collection
Data was collected from Memorial Sloan Kettering Cancer Center’s electronic medical record and picture archiving and communication system. Primary outcomes studied were local tumor progression-free survival (LTPFS) and overall survival (OS). Post-treatment appearance of the lesion was evaluated according to image-guided tumor ablation standard terminology (5).
Technical success was defined as the ablation defect completely covering the target tumor on post-ablation imaging on the day of the ablation. Complete ablation was defined as complete coverage of the target metastasis by the ablation zone on the first post-ablation CT with intravenous contrast and/or positron emission tomography/computed tomography (PET/CT) scan within 4–12 weeks post-ablation. Residual tumor was defined as any new peripheral or nodular enhancement within the ablation zone on the first subsequent CT or any new metabolically active area at the ablation margin on the first subsequent PET/CT. Local progression is defined as the appearance of tumor foci at the edge of the ablation zone after the documentation of complete ablation at the first post-ablation CT with contrast or PET/CT (5). Tumor progression was assessed via Response Evaluation Criteria in Solid Tumors 1.1 or Positron Emission Tomography Response Criteria in Solid Tumors (6,7).
Ablation margin was assessed using MIM MAESTRO® (MIM Software, Inc.) image registration software. Ablation margins were evaluated using pre-procedural and first post-ablation CT scans, 4–8 weeks after ablation. A semi-automatic tool is utilized for margin calculation, which extends the tumor edge by 5 mm for the minimum margin and 10 mm for the optimal margin. The scans are then registered by software personnel, who identify anatomical markers such as the primary bifurcation of the portal vein or areas of calcification, visible on both scans. The ablation margins are then assessed in the follow-up scan and categorized into three groups: 0–4.99 mm, 5–10 mm, or over 10 mm.
Adverse events within 1 month of treatment were graded according to the Common Terminology Criteria for Adverse Events version 5.0 (8).
Statistical analysis
OS was estimated using the Kaplan-Meier method and determined from the time of first treatment to death or last known follow-up. LTPFS was defined as the time period from ablation until radiographic evidence of LTP or last imaging without LTP. LTPFS was analyzed per-tumor. Assisted LTPFS was calculated from the time of the first ablation treatment to the time of the most recent LTP or last imaging without LTP, including tumors that were successfully reablated following identification of LTP. Distant tumor progression-free survival (DTPFS) was defined as the time to development of new hepatic metastases distant from the ablation zone, new extrahepatic disease, or last imaging without distant tumor progression (DTP). Cox proportional hazards model was used to analyze the association between OS, LTPFS, tumor size, subcapsular/perivascular location of the tumor, and ablation margin. Analyses were performed with Stata, version 17 (StataCorp, College Station, Texas).
Results
Technical success was achieved in 100% of tumors in both the RFA and MWA groups. After the first ablation, 3/7 ablated tumors had residual disease (1 RFA, 2 MWA). Outcomes of each treatment are detailed in Table 3.
Table 3
| Patient | Session | Tumor | Ablation type | Ablation margin (mm) | Residual tumor | LTP | LTPFS (months) | OS1 (months) | Death |
|---|---|---|---|---|---|---|---|---|---|
| A | I | 1 | RFA | 5–10 | No | Yes | 3.9 | 14.6 | Yes |
| II | 1* | RFA | 0–4.99 | No | Yes | 3.3 | |||
| III | 2 | RFA | 0–4.99 | Yes | Yes | 2.5 | |||
| B | I | 1 | RFA | 0–4.99 | No | Yes | 2.0 | 43.7 | Yes |
| II | 1* | RFA | 0–4.99 | No | Yes | 13.0 | |||
| III | 1* | RFA | >10 | Yes | Yes | 2.8 | |||
| C | I | 1 | MWA | 0–4.99 | Yes | Yes | 0.5 | 3.0 | Yes |
| D | I | 1 | MWA | 0–4.99 | Yes | Yes | 2.6 | 10.6 | Yes |
| II | 1* | MWA | 5–10 | No | No | 3.4 | |||
| E | I | 1 | MWA | 0–4.99 | No | Yes | 3.2 | 16.8 | Yes |
| F | I | 1 | MWA | 0–4.99 | No | No | 14.2 | 14.3 | No |
*Denotes retreatment of same tumor. 1Survival from the time of ablation. LTP, local tumor progression; LTPFS, local tumor progression-free survival; MWA, microwave ablation; OS, overall survival; RFA, radiofrequency ablation.
The median LTPFS after thermal ablation was 2.9 [95% confidence interval (CI): 0.5–3.9] months (Figure 2). Ablation margin of the treated tumor was not a significant predictor of LTPFS [5–10 vs. 0–4.99 mm, hazard ratio (HR): 0.53; 95% CI: 0.15–1.89, P=0.33]. The median assisted LTPFS, which accounts for tumor control even with subsequent retreatment, was 25.9 [95% CI: 8.3–not reported (NR)] months (Figure 3). The median OS for SCLC was 14.3 (95% CI: 3.0–NR) months (Figure 4). Ablation margin was not a predictor of OS (5–10 vs. 0–4.99 mm, HR: 1.07; 95% CI: 0.11–10.57, P=0.95). The median DTPFS was 8.3 (95% CI: 0.5–NR) months (Figure 5). The mortality rate was 83% (5/6).
Tumor size was not a predictor of LTPFS (HR: 2.08; 95% CI: 0.71–6.11, P=0.18) or OS (HR: 1.08; 95% CI: 0.46–2.54, P=0.86). Similarly, subcapsular location of the tumor was not a predictor of LTPFS (HR: 1.85; 95% CI: 0.33–10.31, P=0.48) or OS (HR: 0.24; 95% CI: 0.02–2.67, P=0.24). Perivascular location of the tumor was not a predictor of LTPFS (HR: 5.50; 95% CI: 0.49–6.08, P=0.17) or OS (HR: 6.52e–17; 95% CI: 0–NR, P>0.99).
There was one grade 1 adverse event after treatment; a patient developed fatigue for a week following MWA, which resolved with rest.
Discussion
This study suggests that thermal ablation for SCLC LMs is safe. While the LTPFS in this study was very modest, the median assisted LTPFS was notably higher at 25.9 months. The relatively short LTPFS is likely secondary to the high number of tumors with residual disease seen on first imaging follow-up. The residual disease is likely a result of the limited ablation margins achieved on most treatments, and based on tumor biology, namely ES-SCLC is marked by widely disseminated disease (9). Surprisingly, the ablation margin was not a predictor of LTPFS or OS; however, this is likely attributable to the very small sample size. In fact, there is a growing body of evidence to support that ablation margins are a strong predictor of tumor recurrence (10). The survival benefits are hard to deduce in this small study; however, the median OS in this study was 14.3 months, which is greater than the median survival of 9–11 months for ES-SCLC with standard treatments (2).
Out of 11 total ablative treatments, there was only one adverse event of fatigue within a month of the MWA (grade 1). The incidence rate of 9.1% is higher than the minor adverse event rate reported for RFA and MWA; however, that is largely attributable to the small sample size (11).
There is a growing body of literature establishing thermal ablation as safe and effective for the treatment of hepatocellular carcinoma and colorectal cancer LMs (4). However, the literature has sparse data for the role of thermal ablation in SCLC LMs. Zhang et al. recently reported that RFA of LMs is a safe locoregional therapy for patients with metastatic lung cancer; however, only 5 of the 58 patients had SCLC (12). This is one of the very few studies dedicated to the safety and efficacy of thermal ablation for LMs in ES-SCLC.
Standard of care for SCLC typically consists of systemic therapies, but locoregional treatment of LMs with thermal ablation should be explored after patients develop resistance to systemic options. This study suggests that there may be a role for multi-disciplinary assessment and discussion of patients with SCLC oligometastases, as these patients may benefit from local ablative therapies.
The limitations of this study include its retrospective nature and small sample size. The study included few patients, treated with different technologies, with different treatment parameters, and by a variety of interventional radiologists with varying years of experience. Additionally, the study spanned over 15 years, during which time treatment paradigms have changed and experience with ablation technology has grown. The sample size was too small to compare whether MWA or RFA has increased LTPFS or OS, and as such, both groups were combined for survival analysis. Notably, RFA was used for treatments on and before 2010, and MWA was utilized for later treatments. This likely reflects a paradigm shift seen at Memorial Sloan Kettering Cancer Center and across the United States at around this time, when MWA was increasingly favored. Despite these limitations, the study provides treatment insights into ablation of LMs for a very understudied disease type.
Conclusions
Thermal ablation for SCLC LMs has few adverse effects. While patients treated with thermal ablation had a very modest LTPFS, the long duration of assisted LTPFS and OS suggest that thermal ablation may be a promising adjunct in the treatment of patients with SCLC.
Acknowledgments
None.
Footnote
Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-112/rc
Peer Review File: Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-112/prf
Funding: This research was funded in part through
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-112/coif). E.Z. has grants from NETRF, NANETS, SIR, ALA, AACR, Ethicon, Novartis, MSK, and TOW Center. C.T.S. has grants from NIH/NCI, SIO, SIR Foundation, SIRTEX, Ethicon J&J, and Boston Scientific; consulting fees from Varian, Ethicon J&J, Terumo, and Covidien; honoraria from Varian and Ethicon J&J; equipment from MIM software. He also has leadership roles in SIR and SIO. S.B.S. has grants from GE Healthcare, consulting fees from GE Healthcare and Merck, stock options in Johnson & Johnson, and has a leadership role in PaigeAI. E.S.A. has consulting fees from Boston Scientific and is the Membership co-chair of the Society of Interventional Oncology. The other authors have no conflicts of interest to declare.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Ethics Committee of Memorial Sloan Kettering Cancer Center (No. 16-402) and individual consent for this retrospective analysis was waived.
Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
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