Biopsy and Margins Optimize Outcomes after Thermal Ablation of Colorectal Liver Metastases

Abstract

Background: Thermal ablation is a definitive local treatment for selected colorectal liver metastases (CLM) that can be ablated with adequate margins. A critical limitation has been local tumor progression (LTP). Methods: This prospective, single-group, phase 2 study enrolled patients with CLM < 5 cm in maximum diameter, at a tertiary cancer center between November 2009 and February 2019. Biopsy of the ablation zone center and margin was performed immediately after ablation. Viable tumor in tissue biopsy and ablation margins < 5 mm were assessed as predictors of 12-month LTP. Results: We enrolled 107 patients with 182 CLMs. Mean tumor size was 2.0 (range, 0.6–4.6) cm. Microwave ablation was used in 51% and radiofrequency ablation in 49% of tumors. The 12- and 24-month cumulative incidence of LTP was 22% (95% confidence interval [CI]: 17, 29) and 29% (95% CI: 23, 36), respectively. LTP at 12 months was 7% (95% CI: 3, 14) for the biopsy tumor-negative ablation zone with margins ≥ 5 mm vs. 63% (95% CI: 35, 85) for the biopsy-positive ablation zone with margins < 5 mm (p < 0.001). Conclusions: Biopsy-proven complete tumor ablation with margins of at least 5 mm achieves optimal local tumor control for CLM, regardless of the ablation modality used.

Interstitial Photothermal Therapy Generates Durable Treatment Responses in Neuroblastoma

“…Although the area at or above the thermal breakpoint of 43 °C includes tissue/skin that may not present a palpable tumor, providing this treatment at areas surrounding the tumor margin could improve the treatment's efficacy to eliminate tumor cells at the margins that are not palpable. [53] Our data suggest that I-PTT can be administered at thermal doses comparable to S-PTT in murine neuroblastoma models. Further, I-PTT heats a larger area at or above the tissue thermal breakpoint.…”

“…The tumor margin has been implicated as the source for tumor recurrence in many ablative therapies, particularly when the ablation/treatment zones do not extend far from the target tumor area. [53,[59][60][61] With PTT, if the thermal ablation area excludes tumor margins, tumor recurrence occurs rapidly. [62] In vivo, when I-PTT was administered to mice-bearing neuroblastoma tumors at equivalent thermal doses to S-PTT (Figures 6 and 7), we observed a significantly reduced rate of tumor recurrence as compared to S-PTT, suggesting the efficacy of I-PTT is not only eradicating tumor but also controlling their margins to reduce the incidence of recurrence.…”

Real-Time Split-Dose PET/CT-Guided Ablation Improves Colorectal Liver Metastasis Detection and Ablation Zone Margin Assessments without the Need for Repeated Contrast Injection

“…A prospective single-arm trial adding biopsy of the AZ immediately after CLM RFA achieved 97% local progression-free survival at 30 months for CLM ablated with tumor-negative biopsy and MM > 5 mm [ 30 ]. A recent, larger study validated these findings for both RFA and microwave ablation with 93% local tumor control at 12 months for biopsy-negative AZ with MM > 5 mm [ 31 ]. For biopsy-proven tumor-negative AZs, the MM size and SUV ratio were predictive surrogate imaging biomarkers of LTP [ 21 ].…”

Colorectal Cancer Liver Metastases: Genomics and Biomarkers with Focus on Local Therapies

“…A robust independent predictor of local tumor progression (LTP) and OS after CRLM ablation is the detection of tumor cells expressing Ki-67 in ablation zone biopsy specimens, suggesting that these tumors may harbor ablation resistance mechanisms [ 149 , 150 , 151 , 152 , 153 ]. Ki-67 positive tumor cells on the electrode after radiofrequency ablation (RFA) of liver tumors is an independent predictor of OS and LTPFS [ 150 , 151 ].…”

“…Although size was thought to be an independent risk factor for LTP in tumors 3–5 cm, it is not as significant of a variable when the data are stratified by margins [ 151 ]. Subsequent prospective trials indicated that the combination of a minimal margin of >5 mm and a negative for tumor biopsy of the ablation zone center and margin offer consistent local tumor control over 97% after RFA [ 149 ] and over 93% for RFA and microwave ablation (MWA) [ 152 ]. In addition, the use of immediate fluorescent stains on ablation zone tissue can detect necrotic versus residual viable tumor intra-procedurally and can predict LTP at 12 months [ 153 ].…”