Colorectal cancer (CRC) is one of the most common cancers worldwide, making it the second leading cause of cancer-related deaths, and it usually metastasizes to the liver by 20% to 40% of patients.^1–4 Survival rates of CRC patients with liver metastasis have increased with the use of metastasectomy, thermal ablation, transarterial chemoembolization, and transarterial radioembolization in addition to current systemic medical treatment options.^5–8

Radiofrequency ablation (RFA) and microwave ablation (MWA) are the most commonly used ablation techniques. Despite studies comparing the efficacy of these techniques in the literature, prospective comparison of the outcome in terms of survival with a broader perspective is scarcely available.⁹ Apart from ablation techniques, concomitant lung metastasis, tumor size, K-ras mutation, prior systemic chemotherapy, and colonic origin of the tumor may also affect survival. There is a need to gather for more evidence in the literature to compare patient survival considering different variables.

The aim of this study is to evaluate the overall survival (OS) and liver progression-free survival (Li-PFS) of CRC patients treated by thermal ablation with RFA and MWA, and effect of different variables such as concomitant lung metastasis, lesion size, local tumor progression (LTP), number of liver metastasis, K-ras mutation, primary tumor location (left- or right-sided), and prior systemic chemotherapy history.

Study design

This study was a retrospective analysis of patients who received RFA or MWA between January 2007 and January 2019 due to CRC liver metastasis. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The Hacettepe University Ethics Committees approved this study (GO-18/429). It is a retrospective study. For this type of study formal consent is not required.

The decision for each thermoablation was made by multidisciplinary institutional tumor board, and informed consent was obtained from all enrolled patients.

The definiton of imaging-guided ablation therapies were defined according to publications developed by the “International Working Group on Image-Guided Tumor Ablation” and “Results of the SIO and DATECAN Initiative”.^10,11

Inclusion criteria

Inclusion criteria for included CRC patients were:

1. Maximum 5 liver metastases and maximum diameter of 5 cm each,

2. Curative intent (ablation of all liver lesions in same session),

3. Presence of magnetic resonance imaging (MRI) images within 2 months before ablation, and follow-up MRI or computed tomography (CT) imaging at 1, 3, 6, 12 months, and semiannually after the first year,

4. The presence of lung metastasis was not an exclusion criterion.

Seventy-one CRC patients who underwent ablation with “curative intent” were identified. MWA was performed in 36 of these patients, and RFA was performed in 35. Since their follow-up was insufficient, three patients treated with MWA and four patients treated with RFA were excluded (9.85% of patients). Finally, the remaining 33 patients (85 metastases) treated with MWA and 31 patients (57 metastases) treated with RFA were enrolled in the study.

Ablation procedure and follow-up

All procedures were done with ultrasound guidance. StarBurst^® (AngioDynamics^®) electrodes were used for RFA, while Acculis^®/Solero^® (AngioDynamics^®) antennas were used for MWA. All procedures were performed according to the manufacturer's instructions for use and with the intention of obtaining an ablation margin of at least 5 mm up to 10 mm.¹² A team of 3 people (O.A., D.A., and T.T.Ç.) with at least 10 years of experience in nonvascular procedures performed all procedures together.

After ablation, contrast-enhanced CT and MRI were performed within the first month. Patients with no residual disease are accepted as “complete ablation,” while the rest as “residue.” Tumor development during follow-up in patients with complete ablation was classified as LTP.

OS was calculated from the final ablation session to death or censored at the final follow-up date. The end date of the observation period was January 28, 2020. Additionally, Li-PFS from the last ablation session to disease progression in the liver with censoring the patients without progression at last imaging was calculated. Since the use of MWA was started in our center initiated in January 2013, the upper limit for survival calculation was set at 7 years to avoid bias between variables. The estimation process for survivals is shown in Fig. 1.

Figure 1. The flowchart of survival estimation process. The flowchart demonstrating the data selection, processes, and end dates for the survival assessments.

Data collection

All data were reviewed and collected by consensus of two radiologists (A.G.E. and O.A.) at two different time points to ensure external and internal validity in both patient selection and data collection.

Ablation index tumor (AIT) refers to the number of tumors in the liver just before ablation. Data on AIT and lung metastasis during ablation as well as the age and sex of patients, presence of K-ras mutation, site of primary disease (right or left colon), prior systemic chemotherapy history, and the survival information were recorded. In addition, the longest axial and craniocaudal diameters of each lesion were measured in the last MRI before ablation.

K-ras mutations were analyzed using DNA derived from formalin-fixed paraffin-embedded tumors obtained from primary sites in the colon. The presence of microsatellite instability was also analyzed.

We followed the suggestion of the "Multidisciplinary Consensus Document from the COLLISION Trial Group", while compiling our data about prior chemotherapy history.¹³ For detailed data including chemotherapy protocols of patients who received systemic chemotherapy prior to ablation, see Table 1. In addition to the planned survival analysis between patients who had received prior systemic chemotherapy and those who had not, a distinction was also made within these subgroups according to lesion size (< 3 cm or ≥ 3–5 cm in diameter). Twenty-five patients had prior systemic chemotherapy and pre-procedural systemic chemotherapy choice was neoadjuvant in all patients while the remainder were given adjuvant chemotherapy.

Table 1 . Detailed Characteristics of Patients with Prior Systemic Chemotherapy.

Patient	RFA/MWA	K-ras oncogene(wild/mutant)	Positivity for any liver lesion 30–50 mm in diameter*	Lung metastasis	Colorectal origin (right/left-sided)	Systemic chemotherapy†
#1	MWA	Mutant	Negative	2	Left	FOLFOX + Bevacizumab
#2	MWA	Mutant	Negative	1	Left	FOLFOX + Bevacizumab
#3	MWA	Mutant	Negative	0	Left	FOLFIRI + Bevacizumab
#4	MWA	Wild	Negative	0	Left	FOLFOX + Cetuximab
#5	MWA	Mutant	Negative	0	Left	FOLFOX + Bevacizumab
#6	MWA	Mutant	Positive	3	Right	FOLFIRI + Bevacizumab
#7	MWA	Mutant	Positive	4	Left	FOLFOX + Bevacizumab
#8	MWA	Mutant	Positive	0	Left	FOLFOX + Bevacizumab
#9	MWA	Wild	Negative	0	Left	FOLFOX + Cetuximab
#10	MWA	Wild	Positive	0	Left	FOLFOX + Panitumumab
#11	MWA	Mutant	Negative	0	Left	FOLFOX + Bevacizumab
#12	MWA	Wild	Positive	1	Left	FOLFOX + Panitumumab
#13	MWA	Wild	Positive	1	Left	FOLFOX + Cetuximab
#14	MWA	Mutant	Positive	5	Left	FOLFIRI + Bevacizumab
#15	MWA	Wild	Negative	3	Left	FOLFOX + Panitumumab
#16	RFA	Wild	Negative	0	Left	FOLFOX + Cetuximab
#17	RFA	Wild	Positive	0	Left	FOLFOX + Cetuximab
#18	RFA	Wild	Negative	0	Left	FOLFOX + Cetuximab
#19	RFA	Wild	Negative	0	Right	FOLFOX + Cetuximab
#20	RFA	Wild	Negative	0	Right	FOLFOX + Panitumumab
#21	RFA	Mutant	Negative	3	Left	FOLFOX + Bevacizumab
#22	RFA	Wild	Negative	0	Left	FOLFOX + Cetuximab
#23	RFA	Wild	Negative	0	Left	FOLFIRI + Panitumumab
#24	RFA	Mutant	Negative	0	Left	FOLFOX + Bevacizumab
#25	RFA	Mutant	Negative	1	Left	FOLFOX + Bevacizumab

RFA, radiofrequency ablation; MWA, microwave ablation; FOLFOX, folinic acid, fluorouracil, and oxaplatin; FOLFIRI, folinic acid, fluorouracil, and irinotecan..

*The patients with liver metastases larger than 30 mm in diameter after systemic chemotherapy..

†The pre-procedural systemic chemotherapy choice was neoadjuvant in all patients. In addition, all patients were partially responsive to prior chemotherapy..

Statistical analysis

Data were processed using IBM-SPSS^® Statistics 24.0 (IBM Corp.), Statacorp LCC-STATA^® 14 software (Stata Corp.) and R^® version 4.0.3 (R Foundation for Statistical Computing). Categorical variables were reported as counts and percentages, and continuous variables as means and standard deviations.

The Kaplan-Meier method was used for estimates of OS and Li-PFS, and the log-rank test was used to compare survival groups. Cox regression models were used to assess the effects of confounding factors on OS. Variables with a P-value of < 0.20 in the univariable analyses were analyzed in multivariable Cox regression models to explore prognostic factors of OS, and the results are reported with hazard ratios (HR) and 95% confidence intervals (CI).

Background

The baseline characteristics of 64 patients and 142 lesions are shown in Fig. 2.

Figure 2. Background data. General background data of thermal ablation is schematized. Ablation index tumor (AIT) number per patient, age and sex distribution, mean values of R-L (right-to-left), A-P (anterior-to-posterior), and C-C (cranial-to-caudal) dimensions of lesions are shown with the largest diameter measured within parenthesis, alongside patients’ distribution with any lesion larger than 30 mm in diameter. MWA, microwave ablation; RFA, radiofrequency ablation; M/F, male/female; LTP, local tumor progression. *Mean diameters are given with standard deviation. Values within parenthesis are maximum diameters.

The median OS was 77.70 months, and the median Li-PFS was 42.00 months. The estimated 1-, 3-, 5-, and 7-year OS rates were 98.4%, 71.2%, 60.1%, and 47.1%, respectively. The estimated 1-, 3-, 5-, and 7-year Li-PFS rates were 77.2%, 52.0%, 42.6%, and 36.9%, respectively.

Survival outcomes considering patient age, sex, AIT and the presence of lesion diameters greater than 30 mm are shown in Table 2. No significant association was found for both OS (P = 0.281) and Li-PFS (P = 0.213), regardless of whether or not the patient had a lesion greater than 30 mm in diameter. When patients with 4–5 AITs were compared with those with 1 AIT and 2–3 AIT, no significant difference was found in OS (P = 0.096). However, a statistically significant difference was found in Li-PFS (P = 0.003).

Table 2 . Associations of Age, Sex, AIT and Presence of a Lesion Diameter Greater than 30 mm with Patient Survival.

	No. of patients (n = 64)	Overall survival				Liver progression-free survival
		Median‡	95% CI	P§		Median‡	95% CI	P§
Sex				0.658				0.614
Male	40	59.54 (4.42)	50.87–68.21			49.31 (5.54)	38.46–60.17
Female	24	62.36 (5.66)	51.25–73.47			43.61 (6.55)	30.76–56.47
Age (yr)				0.450				0.716
< 60	32	62.78 (5.01)	52.95–72.62			58.41 (4.92)	36.81–61.92
≥ 60	32	49.37 (6.40)	48.76–68.05			45.64 (5.73)	34.41–56.87
AIT*				0.096*				0.003*
						52.14 (7.40)	37.63–66.66
1	21	52.82 (5.69)	41.66–63.99
2–3	35	66.30 (4.42)	57.62–74.99			50.62 (5.66)	39.51–61.72
4–5	8	45.80 (8.93)	28.29–63.31			17.56 (5.45)	6.88–28.24
Presence of lesion				0.281				0.213
No lesion < 30 mm	44	66.66 (7.12)	52.70–80.62			51.75 (15.20)	21.95–81.54
Any lesion (30–50 mm)†	20	64.98 (6.01)	53.19–76.76			29.5 (0.48)	28.55–30.44

CI, confidence interval; AIT, ablation index tumor..

*Indicates the effect of 4 or 5 AITs among 3 variables..

†Because of the patient-based nature of the study, all patients with an ablated lesion greater than 30 mm in diameter were included in this group..

‡Median survival rates are presented on a monthly basis. Values in parentheses are the standard error values..

§Log-rank comparison between variables..

After the first ablation, residual tumor was found in 3 lesions during the first month of follow-up (2%). These 3 lesions, out of 15 total, accounted for twenty percent of the tumors with a diameter of 30 to 50 mm treated with RFA (P = 0.034). After detection of residual tumor, these 3 lesions were reablated to achieve complete response in the liver. No significant difference was observed in either OS or Li-PFS according to diameter (P > 0.05).

LTP was diagnosed at 15 patients. The median OS of patients without LTP was 66.94 months, while the median OS of patients with LTP was 51.10 months. A statistically significant correlation was found between any LTP development and OS (P < 0.001), but no correlation was found between ablation technique and LTP (P > 0.05). More detailed information on LTP development is shown in Fig. 2.

Thermoablation technique, K-ras status, and prior systemic chemotherapy

No statistically significant difference was found between the OS of patients who received MWA and the OS of patients who received RFA (P = 0.697). Similarly, no significant difference was observed in Li-PFS (P = 0.122).

The associations of OS and Li-PFS with the variables of chemotherapy, K-ras mutation status, and primary tumor location are shown in Tables 3 and 4. K-ras mutation was significantly associated with shorter OS and Li-PFS (P < 0.001). Although patients with right-sided primary disease had significantly shorter OS (P = 0.025), there was no difference in Li-PFS (P > 0.05).

Table 3 . Association of Variables with Overall Survival.

	No. of patients (n = 64)	Overall survival†
		1-year (%)	3-year (%)	5-year (%)	7-year (%)	Median	95% CI	P‡
Technique								0.697
MWA	33	100	72.6	62.2	41.5	59.39 (4.90)	49.78–68.99
RFA	31	96.8	69.5	57.9	50.2	61.00 (5.01)	51.17–70.83
K-ras oncogene								< 0.001
Wild-type	34	97.1	88.0	80.7	70.6	71.55 (4.13)	63.45–79.66
Mutated	30	100	53.1	38.1	22.9	48.81 (4.82)	39.36–58.25
Prior systemic chemotherapy*								0.613
No	39	97.4	73.5	64.4	47.5	62.60 (4.28)	54.21–70.99
Yes	25	100	67.8	53.8	47.0	57.49 (5.87)	45.98–69.00
Colorectal localization								0.025
Right	16	93.8	62.5	50.0	12.5	49.22 (6.39)	36.68–61.75
Left/rectum	48	100	74.0	64.0	57.0	64.13 (3.93)	56.41–71.85
Lung metastasis								< 0.001
No	49	100	87.4	75.7	59.4	70.03 (3.10)	63.95–76.12
Yes	15	93.3	17.8	0.0	0.0	26.49 (3.18)	20.26–32.73
LTP during follow-up								< 0.001
No	49	85.0	61.0	52.2	45.2	66.94 (4.32)	58.46–75.43
Yes	15	53.3	25.0	0.0	0.0	51.10 (5.28)	40.74–61.45

CI, confidence interval; MWA, microwave ablation; RFA, radiofrequency ablation; LTP, local tumor progression..

*Prior systemic chemotherapy choice was neoadjuvant in all patients (see Table 1)..

†Median survival is shown on a monthly basis, while annual survival is shown as a percentage. Values in parentheses are the standard error values..

‡Log-rank comparisons between variables..

Table 4 . Associations of Variables with Liver Progression-free Survival.

	No. of patients (n = 64)	Liver progression-free survival†
		1-year (%)	3-year (%)	5-year (%)	7-year (%)	Median	95% CI	P‡
Technique								0.122
MWA	33	75.3	44.8	35.9	23.1	41.22 (5.60)	30.25–52.20
RFA	31	79.3	60.3	50.3	50.3	53.43 (6.28)	41.11–65.74
K-ras oncogene								< 0.001
Wild-type	34	81.4	71.2	71.2	64.7	62.24 (5.86)	50.75–73.73
Mutated	30	79.7	32.7	14.0	9.4	31.90 (4.47)	23.13–40.67
Prior systemic chemotherapy*								0.665
No	39	81.5	52.8	45.7	37.2	48.47 (5.35)	37.96–58.97
Yes	25	70.8	51.0	37.2	37.2	45.02 (7.11)	31.07–58.97
Colorectal localization								0.144
Right	16	68.8	40.1	30.1	20.1	35.80 (6.68)	22.70–48.90
Left/rectum	48	80.3	56.4	47.3	43.4	50.36 (5.00)	40.56–60.17
Lung metastasis								< 0.001
No	49	85.0	61.0	52.2	45.2	54.04 (4.74)	44.73–63.34
Yes	15	53.3	25.0	0.0	0.0	21.96 (4.88)	12.39–31.53

CI, confidence interval; MWA, microwave ablation; RFA, radiofrequency ablation..

*Prior systemic chemotherapy choice was neoadjuvant in all patients (see Table 1)..

†Median survival is shown on a monthly basis, while annual survival is shown as a percentage. Values in parentheses are standard error values..

‡Log-rank comparison between variables..

Although microsatellite instability was also analyzed in all patients included in the study, it was not detected in any of them.

Twenty-five patients had prior systemic chemotherapy and pre-procedural systemic chemotherapy choice was neoadjuvant in all patients (Table 1). The effects of neoadjuvant chemotherapy and the effects of K-ras mutations on survival are detailed in Fig. 3. No statistically significant difference in OS and Li-PFS was observed in patients with lesions less than 30 mm in diameter who had prior systemic chemotherapy or not (P = 0.27 and P = 0.42, respectively). Similarly, no statistically significant difference was found in both OS and Li-PFS in patients 3–5 cm in diameter (P = 0.069 and P = 0.71, respectively), although it was marginally non-significant for OS. More detailed information is shown in Fig. 4.

Figure 3. Survival charts in regard of chemotherapy and K-ras mutation. Overall survival (A, B) and liver progression-free survival (C, D) charts according to wild or mutated K-ras oncogene and whether neoadjuvant chemotherapy is administired or not prior to thermal ablation. Emphatic effect of mutated K-ras oncogene is clearly observed (A, C), while no significant effect of neoadjuvant chemotherapy for liver metastasis on survival is observed (B, D).

Figure 4. Survival charts considering diameter and chemotherapy. Overall survival (OS) of patients with ablated tumors less than 3 cm (A) and 3–5 cm (B). Liver progression-free survival (Li-PFS) of patients with ablated tumors less than 3 cm (C) and 3–5 cm (D). CI, confidence interval; NA, not applicable.

Concomitant lung metastasis

Patients with concomitant lung metastasis had a significantly shorter OS and Li-PFS (P < 0.001). Detailed information on lung metastases during ablation is shown in Tables 3, 4, and Fig. 5. Of the patients with concomitant lung metastasis, five patients (three patients had one metastasis and two patients each had two metastases) received MWA for lung metastases, and two patients (one had one metastasis and the other had three metastases) underwent surgery. The remaining patients were treated with systemic chemotherapy.

Figure 5. Survival chart of patients with concomittant lung metastasis. Background data of 15 patients with lung metastases during liver ablation are shown along with the OS chart of patients with lung metastases during thermal liver ablation. OS, overall survival; MWA, microwave ablation; CI, confidence interval; NA, not applicable.

Multivariable analysis

The results of the multivariable analysis are shown in Table 5.

Table 5 . Multivariable Analysis of the Effects of Variables on Survival*.

	Overall survival				Liver progression-free survival
	HR	95% CI	P		HR	95% CI	P
Mutated K-ras oncogene	1.703	0.819–3.542	0.154		1.634	0.608–4.390	0.330
Right colon cancer	2.276	1.034–5.007	0.041		1.316	0.543–3.193	0.543
Lung metastasis	12.561	4.568–34.540	< 0.001		3.689	1.588–8.567	0.002
AIT, 4–5†	1.127	0.350–3.630	0.841		3.382	1.183–9.673	0.023
LTP during follow-up‡	1.547	0.674–3.551	0.303		NA	NA	NA

HR, hazard ratio; CI, confidence interval; AIT, ablation index tumor; LTP, local tumor progression; NA, not applicable..

*Only variables with P < 0.20 values were included in the multivariate analysis..

†Comparisons of 4 or 5 AITs with multiple variables..

‡LTP is an event that terminates progression-free survival, and because it consequently causes high HR and bias, this parameter was not included in the multivariate analysis..

Lung metastases were found to be the variable with the largest negative effect on OS (P < 0.001, HR = 12.561), followed by metastases originating from the right colon (P = 0.041, HR = 2.276). Mutated K-ras oncogene (P = 0.154, HR = 1.703), LTP during follow-up (P = 0.303, HR = 1.547), and 4–5 AIT (P = 0.841, HR = 1.127) were not found as statistically significant for OS.

For Li-PFS, lung metastasis was the variable with the largest effect (P = 0.002, HR = 3.689), followed by the presence of 4–5 AITs (P = 0.023, HR = 3.382). Mutated K-ras oncogene (P = 0.330, HR = 1.634) and metastases originated from the right colon (P = 0.543, HR = 1.316) were not found as statistically significant for Li-PFS.

Our results showed that in patients with liver metastasis of CRC, there is no significant difference between RFA and MWA in terms of OS and Li-PFS. OS was shorter in patients with lung metastasis and right-sided primary disease, whereas lung metastasis and having more than 3 liver metastases were associated with shorter Li-PFS.

Although residual viable tumors were seen in patients who underwent RFA (3 patients), all of which were larger than 3 cm and ablated in a second session, there was no correlation between LTP during follow-up and ablation technique. LTP development was noted in 15 patients during follow-up, and of these, 8 were treated with RFA and 7 with MWA. There are different reports on this topic in the literature. A retrospective study that compared MWA and RFA in 134 patients; relatively rare LTP was reported for MWA.¹⁴ But, the significantly shorter follow-up in MWA group was an important limitation in that study. Another study compared thermoablation techniques (including laser ablation) and found no difference in the 1-, 3-, and 5-year survival rates,¹⁵ similar to our results, but more evidence is required in comparison of RFA and MWA. Nevertheless, LTP development was found to be a significant variable for OS regardless of the technique.

Nieuwenhuizen et al¹³ recently reported Multidisciplinary Consensus Document from the COLLISION Trial Group. In that paper, there is a broad consensus that liver metastases less than 3 cm in diameter can be treated locally without the need for pre-procedural chemotherapy. In addition, a strong consensus was reached in that report as locoregional treatment should be performed after chemotherapy for tumors 3 to 5 cm in diameter.^16–20 However, liver metastasis remains to be leading cause of mortality in patients with CRC. The role of chemotherapy in metastatic CRC is undisputed and imperative, in patients with limited disease in liver, thermal ablation is an established therapy option.²¹ In our study, we found no significant difference between subgroups, including tumor diameter and administration of prior systemic chemotherapy. Although OS was lower in our patients with a lesion 3 to 5 cm in diameter who had not prior systemic chemotherapy, this failed to reach statistical significance. One reason for this could be that all patients in our study received "neoadjuvant" chemotherapy before the procedure and all also responded to chemotherapy (Table 1). Also, our finding supports the results of COLLISION trial.

K-ras mutation status was found to be negative prognostic factor for OS and Li-PFS in our study. In the amCORE—Amsterdam Colorectal Liver Met Registry—study, CRC patients who had undergone surgical resection or ablation treatment were studied considering their tumor biology.²² They found no difference for OS considering K-ras mutation, while Li-PFS was significantly lower in the group with mutated K-ras. No statistical difference for OS and LTP was also found with respect to the primary origin of the CRC in the amCORE study. However, K-ras mutation status was not known in 84% of the patients and half of the patients underwent surgery (either alone or combined with ablation).²² Zhou et al²³ examined the 10-year local progression-free survival in patients treated with MWA and found that local progression-free survival was decreased in metastases that originated from the right colon. Gu et al²⁴ also reported a similar correlation in 102 patients who underwent RFA, and concluded that patients with tumors originating from the left colon had better survival outcomes. Also in our study, a significant decrease in OS was noted in right-sided colon cancer. This may underline the need for additional therapeutic measures in those patients. In addition, Li-PFS was significantly shorter in patients with right-sided primary disease, although the difference was not significant in multivariable analysis.

Considering prior systemic chemotherapy, there was no significant benefit in OS and Li-PFS regardless of K-ras mutation status. To our knowledge, there is no other study in the literature on neoadjuvant chemotherapy administration that also considers both thermoablation techniques and the K-ras mutation. However, it is also a fact that it is difficult to draw a conclusion with this retrospective study. The need for higher evidence and prospective randomized trials is clear. It should also be noted that the patients included in the study were able to have a dısease-free liver condition. For this reason, generalization of these results to all patients receiving prior systemic chemotherapy could cause selection bias.

The presence of lung metastases is known to be a factor that decreases OS.^25,26 Shady et al²⁵ reported that the presence of extrahepatic metastases was asserted as one of the most important factors in reducing the survival rate of CRC patients whose metastases were treated with RFA. In our study, the presence of lung metastases had a significant impact on OS and Li-PFS and was found to be more important than primary site and K-ras mutations, suggesting that concomitant lung metastases may be an important overall indicator of aggresive biologic behavior of tumor. In addition, a higher survival rate was observed in patients with concomitant lung metastases who were able to achieve disease-free status of lungs. This may indicate the importance of maintaining a disease-free state in patients with concomitant lung metastases, and pursuing additional lung-directed therapies. However, considering our results, the small sample size is noteworthy and indicative of further studies.

This study has some limitations. First, this is a single center, retrospective study with a relatively small cohort. However, it represents results from a large volume tertiary oncology center with established thermal ablation protocol. Additionally, the median OS of the entire study population was 77.70 months, and the median Li-PFS was 42.00 months similar to those reported in the literature, which represents validity of the cohort.^27–30 Second, only the presence of a K-ras mutation was considered, and no other mutations such as N-Ras, BRAF, or microsatellite instability were included in our study. However, our study provides an appropriate basis for future studies on thermal ablation for liver metastasis of CRC.

In conclusion, concomitant lung metastasis appears to be the most important factor reducing both OS and Li-PFS, and it was observed that survival was relatively high in patients whose lung metastases were treated invasively. As no significant difference in survival was found with thermal ablation techniques, the similar results were observed between adjuvant-only and neoadjuvant chemotherapy. Host-specific variables such as K-ras mutation, site of primary disease, and lung metastasis may also play pivot role in better treatment outcomes. Therefore, prospective randomized trials are needed to better understand the exact effects.

The data that support the findings of this study are available from the corresponding author upon reasonable request.

None.

No potential conflict of interest relevant to this article was reported.