Primary Tumor Sidedness, RAS and BRAF Mutations and MSI Status as Prognostic Factors in Patients with Colorectal Liver Metastases Treated with Surgery and Thermal Ablation: Results from the Amsterdam Colorectal Liver Met Registry (AmCORE)

The aim of this study was to assess primary tumor sidedness of colorectal cancer (CRC), rat sarcoma viral oncogene homolog (RAS) and v-raf murine sarcoma viral oncogene homolog B (BRAF) mutations and microsatellite instability (MSI) status as prognostic factors predicting complications, survival outcomes, and local tumor progression (LTP) following surgery and thermal ablation in patients with colorectal liver metastases (CRLM). This Amsterdam Colorectal Liver Met Registry (AmCORE) based study included 520 patients, 774 procedures, and 2101 tumors undergoing local treatment (resection and/or thermal ablation) from 2000 to 2021. Outcomes following local treatment were analyzed for primary tumor sidedness of CRC, RAS, and BRAF mutations and MSI status. The Kaplan–Meier method was used to estimate local tumor progression-free survival (LTPFS), local control (LC), distant progression-free survival (DPFS), and overall survival (OS). Uni- and multivariable analyses were performed based on Cox proportional hazards model. The chi-square test was used to analyze complications. Complications (p = 0.485), OS (p = 0.252), LTPFS (p = 0.939), and LC (p = 0.423) was not associated with tumor-sidedness. Compared to right-sided colon cancer (CC) (reference HR 1.000), DPFS was superior for left-sided CC and rectal cancer (p = 0.018) with an HR for left-sided CC of 0.742 (95% CI, 0.596–0.923) and for RC of 0.760 (95% CI, 0.597–0.966). Regarding RAS mutations, no significant difference was found in OS (p = 0.116). DPFS (p = 0.001), LTPFS (p = 0.039), and LC (p = 0.025) were significantly lower in the RAS mutation group. Though no difference in LTPFS was found between RAS wildtype and RAS mutated CRLM following resection (p = 0.532), LTPFS was worse for RAS mutated tumors compared to RAS wildtype following thermal ablation (p = 0.037). OS was significantly lower in the BRAF mutation group (p < 0.001) and in the MSI group (p < 0.001) following local treatment, while both did not affect DPFS, LTPFS, and LC. This AmCORE based study suggests the necessity of wider margins to reduce LTP rates in patients with RAS mutated CRLM, especially for thermal ablation. Upfront knowledge regarding molecular biomarkers may contribute to improved oncological outcomes.

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Thermal Ablation Compared to Partial Hepatectomy for Recurrent Colorectal Liver Metastases: An Amsterdam Colorectal Liver Met Registry (AmCORE) Based Study

Cancers ◽

10.3390/cancers13112769 ◽

2021 ◽

Vol 13 (11) ◽

pp. 2769

Author(s):

Madelon Dijkstra ◽

Sanne Nieuwenhuizen ◽

Robbert S. Puijk ◽

Florentine E.F. Timmer ◽

Bart Geboers ◽

...

Keyword(s):

Liver Metastases ◽

Hospital Stay ◽

Partial Hepatectomy ◽

Thermal Ablation ◽

Colorectal Liver Metastases ◽

Local Treatment ◽

Length Of Hospital Stay ◽

Progression Free Survival ◽

Free Survival ◽

Subgroup Analyses

The aim of this study was to assess safety, efficacy and survival outcomes of repeat thermal ablation as compared to repeat partial hepatectomy in patients with recurrent colorectal liver metastases (CRLM). This Amsterdam Colorectal Liver Met Registry (AmCORE) based study of two cohorts, repeat thermal ablation versus repeat partial hepatectomy, analyzed 136 patients (100 thermal ablation, 36 partial hepatectomy) and 224 tumors (170 thermal ablation, 54 partial hepatectomy) with recurrent CRLM from May 2002 to December 2020. The primary and secondary endpoints were overall survival (OS), distant progression-free survival (DPFS) and local tumor progression-free survival (LTPFS), estimated using the Kaplan–Meier method, and complications, analyzed using the chi-square test. Multivariable analyses based on Cox proportional hazards model were used to account for potential confounders. In addition, subgroup analyses according to patient, initial and repeat local treatment characteristics were performed. In the crude overall comparison, OS of patients treated with repeat partial hepatectomy was not statistically different from repeat thermal ablation (p = 0.927). Further quantification of OS, after accounting for potential confounders, demonstrated concordant results for repeat local treatment (hazard ratio (HR), 0.986; 95% confidence interval (CI), 0.517–1.881; p = 0.966). The 1-, 3- and 5-year OS were 98.9%, 62.6% and 42.3% respectively for the thermal ablation group and 93.8%, 74.5% and 49.3% for the repeat resection group. No differences in DPFS (p = 0.942), LTPFS (p = 0.397) and complication rate (p = 0.063) were found. Mean length of hospital stay was 2.1 days in the repeat thermal ablation group and 4.8 days in the repeat partial hepatectomy group (p = 0.009). Subgroup analyses identified no heterogeneous treatment effects according to patient, initial and repeat local treatment characteristics. Repeat partial hepatectomy was not statistically different from repeat thermal ablation with regard to OS, DPFS, LTPFS and complications, whereas length of hospital stay favored repeat thermal ablation. Thermal ablation should be considered a valid and potentially less invasive alternative for small-size (0–3 cm) CRLM in the treatment of recurrent new CRLM. While, the eagerly awaited results of the phase III prospective randomized controlled COLLISION trial (NCT03088150) should provide definitive answers regarding surgery versus thermal ablation for CRLM.

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Repeat Local Treatment of Recurrent Colorectal Liver Metastases, the Role of Neoadjuvant Chemotherapy: An Amsterdam Colorectal Liver Met Registry (AmCORE) Based Study

Cancers ◽

10.3390/cancers13194997 ◽

2021 ◽

Vol 13 (19) ◽

pp. 4997

Author(s):

Madelon Dijkstra ◽

Sanne Nieuwenhuizen ◽

Robbert S. Puijk ◽

Florentine E. F. Timmer ◽

Bart Geboers ◽

...

Keyword(s):

Neoadjuvant Chemotherapy ◽

Hospital Stay ◽

Colorectal Liver Metastases ◽

Local Treatment ◽

Length Of Hospital Stay ◽

Progression Free Survival ◽

Free Survival ◽

Significant Difference ◽

Subgroup Analyses

This cohort study aimed to evaluate efficacy, safety, and survival outcomes of neoadjuvant chemotherapy (NAC) followed by repeat local treatment compared to upfront repeat local treatment of recurrent colorectal liver metastases (CRLM). A total of 152 patients with 267 tumors from the prospective Amsterdam Colorectal Liver Met Registry (AmCORE) met the inclusion criteria. Two cohorts of patients with recurrent CRLM were compared: patients who received chemotherapy prior to repeat local treatment (32 patients) versus upfront repeat local treatment (120 patients). Data from May 2002 to December 2020 were collected. Results on the primary endpoint overall survival (OS) and secondary endpoints local tumor progression-free survival (LTPFS) and distant progression-free survival (DPFS) were reviewed using the Kaplan–Meier method. Subsequently, uni- and multivariable Cox proportional hazard regression models, accounting for potential confounders, were estimated. Additionally, subgroup analyses, according to patient, initial and repeat local treatment characteristics, were conducted. Procedure-related complications and length of hospital stay were compared using chi-square test and Fisher’s exact test. The 1-, 3-, and 5-year OS from date of diagnosis of recurrent disease was 98.6%, 72.5%, and 47.7% for both cohorts combined. The crude survival analysis did not reveal a significant difference in OS between the two cohorts (p = 0.834), with 1-, 3-, and 5-year OS of 100.0%, 73.2%, and 57.5% for the NAC group and 98.2%, 72.3%, and 45.3% for the upfront repeat local treatment group, respectively. After adjusting for two confounders, comorbidities (p = 0.010) and primary tumor location (p = 0.023), the corrected HR in multivariable analysis was 0.839 (95% CI, 0.416–1.691; p = 0.624). No differences between the two cohorts were found with regards to LTPFS (HR = 0.662; 95% CI, 0.249–1.756; p = 0.407) and DPFS (HR = 0.798; 95% CI, 0.483–1.318; p = 0.378). No heterogeneous treatment effects were detected in subgroup analyses according to patient, disease, and treatment characteristics. No significant difference was found in periprocedural complications (p = 0.843) and median length of hospital stay (p = 0.600) between the two cohorts. Chemotherapy-related toxicity was reported in 46.7% of patients. Adding NAC prior to repeat local treatment did not improve OS, LTPFS, or DPFS, nor did it affect periprocedural morbidity or length of hospital stay. The results of this comparative assessment do not substantiate the routine use of NAC prior to repeat local treatment of CRLM. Because the exact role of NAC (in different subgroups) remains inconclusive, we are currently designing a phase III randomized controlled trial (RCT), COLLISION RELAPSE trial, directly comparing upfront repeat local treatment (control) to neoadjuvant systemic therapy followed by repeat local treatment (intervention).

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Predictors of Progression-Free Survival and Local Tumor Control after Percutaneous Thermal Ablation of Oligometastatic Breast Cancer: Retrospective Study

Journal of Vascular and Interventional Radiology ◽

10.1016/j.jvir.2020.02.016 ◽

2020 ◽

Vol 31 (8) ◽

pp. 1201-1209

Author(s):

Fourat Ridouani ◽

Stephen B. Solomon ◽

Yolanda Bryce ◽

Jacqueline F. Bromberg ◽

Constantinos T. Sofocleous ◽

...

Keyword(s):

Breast Cancer ◽

Retrospective Study ◽

Thermal Ablation ◽

Progression Free Survival ◽

Local Tumor Control ◽

Tumor Control ◽

Local Tumor ◽

Free Survival ◽

Percutaneous Thermal Ablation

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Neoadjuvant Chemotherapy Followed by Radiofrequency Ablation Prolongs Survival for Ablatable Colorectal Liver Metastasis: A Propensity Score Matching Comparative Study

Frontiers in Oncology ◽

10.3389/fonc.2021.758552 ◽

2021 ◽

Vol 11 ◽

Author(s):

Yizhen Chen ◽

Youyao Xu ◽

Linwei Xu ◽

Fang Han ◽

Yurun Huang ◽

...

Keyword(s):

Radiofrequency Ablation ◽

Liver Metastasis ◽

Neoadjuvant Chemotherapy ◽

Propensity Score ◽

Tumor Progression ◽

Propensity Score Matching ◽

Progression Free Survival ◽

Local Tumor Progression ◽

Local Tumor ◽

Free Survival

BackgroundTypically, colorectal liver metastasis (CRLM) is not a candidate for hepatectomy. Radiofrequency ablation (RFA) plays a critical role in unresectable CRLM patients. Nevertheless, high local tumor progression (LTP) and distant metastasis limit the development and further adoption and use of RFA. Neoadjuvant chemotherapy (NAC) has been widely used in resectable CRLM and is recommended by the guidelines. There are no studies on whether NAC can improve the prognosis in ablatable CRLM patients. The present study aimed to determine the feasibility and effectiveness of RFA plus NAC.MethodsThis retrospective cohort included CRLM patients from Zhejiang Cancer Hospital records, who received RFA from January 2009 to June 2020 and were divided into two groups according to the presence or absence of NAC. The Kaplan–Meier method was used to evaluate the 3-year local tumor progression-free survival (LTPFS), progression-free survival (PFS), and overall survival (OS) of the two groups. The propensity score matching was used to reduce bias when assessing survival. Multivariate Cox proportional hazards regression analysis was used to study the independent factors affecting LTPFS, PFS, and OS.ResultsA total of 149 CRLM patients (88 in the RFA alone group and 61 in the plus NAC group) fulfilled the inclusion criteria. Post-RFA complications were 3.4% in the RFA alone group and 16.4% in the plus NAC group. The 3-year LTPFS, PFS, and OS of the RFA only group were 60.9%, 17.7%, and 46.2%, respectively. The 3-year LTPF, PFS, and OS of the plus NAC group were 84.9%, 46.0%, and 73.6%, respectively. In the 29 pairs of propensity score matching cohorts, the 3-year LTPFS, PFS, and OS in the plus NAC group were longer than those in the RFA group (P < 0.05). NAC was an independent protective factor for LTPFS, PFS, and OS (P < 0.05).ConclusionsFor ablatable CRLM patients, RFA plus NAC obtained a better prognosis than RFA alone. Based on the current results, the application of NAC before RFA may become the standard treatment.

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CT-Based Radiomics Analysis Before Thermal Ablation to Predict Local Tumor Progression for Colorectal Liver Metastases

CardioVascular and Interventional Radiology ◽

10.1007/s00270-020-02735-8 ◽

2021 ◽

Author(s):

Marjaneh Taghavi ◽

Femke Staal ◽

Fernando Gomez Munoz ◽

Farshad Imani ◽

David B. Meek ◽

...

Keyword(s):

Liver Metastases ◽

Tumor Progression ◽

Thermal Ablation ◽

Colorectal Liver Metastases ◽

Local Tumor Progression ◽

Local Tumor

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Volumetric 3D assessment of ablation zones after thermal ablation of colorectal liver metastases to improve prediction of local tumor progression

European Radiology ◽

10.1007/s00330-018-5809-0 ◽

2018 ◽

Vol 29 (5) ◽

pp. 2698-2705 ◽

Cited By ~ 14

Author(s):

Elena A. Kaye ◽

Francois H. Cornelis ◽

Elena N. Petre ◽

Neelam Tyagi ◽

Waleed Shady ◽

...

Keyword(s):

Liver Metastases ◽

Tumor Progression ◽

Thermal Ablation ◽

Colorectal Liver Metastases ◽

Local Tumor Progression ◽

Local Tumor

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Clinical Outcomes and Predictors in Patients With Unresectable Colorectal Cancer Liver Metastases Following Salvage Percutaneous Radiofrequency Ablation: A Single Center Preliminary Experience

Technology in Cancer Research & Treatment ◽

10.1177/1533033820963662 ◽

2020 ◽

Vol 19 ◽

pp. 153303382096366

Author(s):

Ying Wang ◽

Guang-Yuan Zhang ◽

Li-Chao Xu ◽

Xin-Hong He ◽

Hao-Zhe Huang ◽

...

Keyword(s):

Colorectal Cancer ◽

Radiofrequency Ablation ◽

Liver Metastases ◽

Tumor Progression ◽

Survival Time ◽

Progression Free Survival ◽

Local Tumor Progression ◽

Local Tumor ◽

Colorectal Cancer Liver Metastases ◽

Free Survival

Purpose: The purpose of this study was to investigate the clinical efficacy of salvage percutaneous radiofrequency ablation in patients with unresectable colorectal cancer liver metastases. Methods: The cohort consisted of 81 patients with 126 colorectal cancer liver metastases who underwent radiofrequency ablation between January 2012 and September 2016. The clinical data and ablation data were retrospectively analyzed. The local tumor progression-free survival, overall survival, and prognostic factors were analyzed using the log-rank test and Cox regression model. Results: The technique success rate was 99.21%. The primary efficacy rate was 100% at the 1-month follow-up. Minor complications were observed in 2 patients, which recovered within 1 week. The median local tumor progression-free survival time of all patients was 29.8 months. The absence of subsequent chemotherapy was an independent predictor of a shorter local tumor progression-free survival time ( P < 0.001, hazard ratio: 2.823, 95% confidence interval: 1.603, 4.972). The median overall survival time was 26.8 months. A lesion size greater than 3 cm ( P = 0.011, hazard ratio: 2.112, 95% confidence interval: 1.188, 3.754) and the presence of early local tumor progression ( P = 0.011, hazard ratio: 2.352, 95% confidence interval: 1.217, 4.545) were related to a shorter survival time. Conclusions: Percutaneous radiofrequency ablation is safe in patients with colorectal cancer liver metastases refractory from chemotherapy. Subsequent chemotherapy is important to enhance local control. Small lesions and favorable early responses are related to prolonged overall survival.

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Radiotherapy in nodal oligorecurrent prostate cancer

Strahlentherapie und Onkologie ◽

10.1007/s00066-021-01778-1 ◽

2021 ◽

Author(s):

Michael Pinkawa ◽

Daniel M. Aebersold ◽

Dirk Böhmer ◽

Michael Flentje ◽

Pirus Ghadjar ◽

...

Keyword(s):

Prostate Cancer ◽

Literature Review ◽

Survival Rates ◽

Local Treatment ◽

Progression Free Survival ◽

Nodal Metastasis ◽

Stereotactic Ablative Radiotherapy ◽

Current Standard ◽

Free Survival ◽

Systemic Treatments

Abstract Objective The current article encompasses a literature review and recommendations for radiotherapy in nodal oligorecurrent prostate cancer. Materials and methods A literature review focused on studies comparing metastasis-directed stereotactic ablative radiotherapy (SABR) vs. external elective nodal radiotherapy (ENRT) and studies analyzing recurrence patterns after local nodal treatment was performed. The DEGRO Prostate Cancer Expert Panel discussed the results and developed treatment recommendations. Results Metastasis-directed radiotherapy results in high local control (often > 90% within a follow-up of 1–2 years) and can be used to improve progression-free survival or defer androgen deprivation therapy (ADT) according to prospective randomized phase II data. Distant progression after involved-node SABR only occurs within a few months in the majority of patients. ENRT improves metastases-free survival rates with increased toxicity in comparison to SABR according to retrospective comparative studies. The majority of nodal recurrences after initial local treatment of pelvic nodal metastasis are detected within the true pelvis and common iliac vessels. Conclusion ENRT with or without a boost should be preferred to SABR in pelvic nodal recurrences. In oligometastatic prostate cancer with distant (extrapelvic) nodal recurrences, SABR alone can be performed in selected cases. Application of additional systemic treatments should be based on current guidelines, with ADT as first-line treatment for hormone-sensitive prostate cancer. Only in carefully selected patients can radiotherapy be initially used without additional ADT outside of the current standard recommendations. Results of (randomized) prospective studies are needed for definitive recommendations.

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