To investigate the effectiveness and safety of microwave ablation (MWA) in patients with 1-5 colorectal liver metastases (CRLM) versus those with 6-9 CRLM.

Data from patients with 1-9 CRLM, who underwent ultrasound (US)-guided percutaneous MWA between January 2018 and May 2023, were retrospectively analyzed. Propensity score matching (PSM) at a ratio of 1:2 was used to balance potential bias between the groups.

Data from 264 patients were included in the analysis. After PSM, there were 43 and 75 patients in the CRLM >5 and ≤5 groups, respectively. Even with higher tumor burden and technical difficulty, there was no statistical difference in the local tumor progression (LTP)-free survival (LTPFS) between the groups (p > 0.05). Patients with an ablation margin (AM) ≤5 mm exhibited a significantly higher rate of LTP than those with AM >5 mm in both groups(p < 0.05). Patients with 6-9 CRLM experienced a higher incidence of intrahepatic recurrence (iHR) (p = 0.041) and shorter progression-free survival (PFS) at any site (p < 0.05). CRLM > 5 is an independent risk factor for poor PFS (p = 0.008). The minor complication rate was lower in the CRLM ≤ 5 group (p < 0.05) and the major complication rate showed no difference (p > 0.05).

When the number of CRLM was limited to 9, single-session MWA was feasible and safe for radical local treatment. An AM >5 mm was critical for local tumor control. Compared with patients with 1-5 CRLM, those with 6-9 CRLM experienced inferior PFS at any site, which mainly lies in more iHR.

The optimal strategy for patients with colorectal liver metastases is still controversially discussed. This study aimed to evaluate the efficacy of radiofrequency ablation (RFA) combined with systemic chemotherapy plus targeted therapy as first-line treatment in patients with initially unresectable colorectal liver metastases (CRLM), to identify prognostic factors and construct nomograms predicting survival.

This retrospective study included patients with initially unresectable CRLM treated with (study group n = 74) or without (control group n = 83) RFA at the National Cancer Center from January 2018 to January 2021. Survival curves were assessed using the Kaplan-Meier method and log-rank test. Univariate and multivariate Cox regression analyses were used to determine prognostic factors and include these factors in the nomograms to predict progression-free survival (PFS) and overall survival (OS).

The study group had significantly better median PFS (17.16 months vs. 8.35 months, p < 0.01) and OS (34.9 months vs. 21.1 months, p < 0.01) than the control group after propensity score matching. Cox regression analyses identified RFA treatment and clinical risk score (CRS) as independent prognostic factors for PFS. The largest diameter of liver metastases, RFA treatment, and CRS were independent prognostic factors for OS. Based on this finding, nomograms with good discrimination and calibration were constructed.

RFA combined with systemic chemotherapy plus targeted therapy as first-line treatment could significantly prolong PFS and OS in patients with initially unresectable CRLM compared with systemic chemotherapy plus targeted therapy. The nomograms predicting PFS and OS might help clinicians select personalized treatment.

The management of colorectal cancer (CRC) is a complex process. Defining the disease burden, assessing the radiological response and identifying the right time for surgery or other locoregional treatments are crucial factors which can require the involvement of a multidisciplinary tumor board (MDTB) comprising several specialists. This study investigates the impact of MDTB on management of CRC in our institution.

We retrospectively assessed all cases discussed by our MDTB between September 2019 and April 2023. In particular, we collected data concerning radiology, surgery and radiotherapy indication before and after MDTB meetings. The primary endpoint was the overall rate of discrepancy between pre- and post-discussion evaluations.

Our analysis involved 1150 cases. Median age was 64 years (16-90), 629 patients (54.7%) were male and 915 (79.5%) had metastatic disease at the time of the relevant MDTB discussion. After the meetings, 325 treatment decisions were modified, producing an overall discrepancy rate of 28.3%. In particular: (1) of 648 cases discussed for radiological assessment, 156 decisions (24.1%) were altered after a central imaging review; (2) of 327 cases considered for surgical approach, treatment strategy changed in 118 (36.1%); and (3) of the 160 cases discussed regarding radiotherapy, the treatment strategy changed in 51 of them (31.9%).

Our analysis shows significant discrepancies between the radiology and locoregional evaluations from both before and after the MDTB meetings. Our results highlight that the discussions of a MDTB can considerably change the management of CRC, maximizing the treatment strategy.

In pancreatic cancer, therapeutic investigations targeting liver metastases could improve survival. However, the use of local treatment for oligometastasis in pancreatic cancer remains controversial. This study aimed to investigate the oncological role of local therapy in patients who underwent curative pancreatectomy and subsequently developed liver metastases.

Data concerning patients who underwent curative pancreatectomy for pancreatic cancer at Severance Hospital in Seoul, South Korea between 2006 and 2018 were retrospectively reviewed. We included patients with one or two liver metastases, as confirmed on imaging. We excluded those with metastases in other organs. The patients were divided into two groups: the NT group, receiving conventional therapy without local treatment; and the LT group, receiving local treatments for liver metastases alongside standard therapy.

Of the 43 included patients (NT group, n=33; LT group, n=10), no significant differences were observed in overall survival (OS) [hazard ratio (HR) 0.846; 95% confidence interval (CI) 0.397-1.804; p=0.665] or post-recurrence survival (HR 0.932; 95% CI 0.437-1.985, p=0.855) between the two groups. In multivariate analysis, early recurrence within 6 months (p<0.001) and the use of 5-fluorouracil (FU)-based adjuvant chemotherapy (CTx) (p=0.011), as well as 5-FU-based CTx after liver metastasis (p=0.008) when compared with gemcitabine-based regimens, were significant predictors of poor OS.

The oncologic role of local treatment for hepatic metastasis remains controversial in patients with hepatic metastasis after radical pancreatectomy. In the era of potent chemotherapeutic regimens, further research is needed to clarify the efficacy of such regimens.

For patients with colorectal cancer liver metastasis (CRCLM), curative-intent liver therapies are associated with improved survival. However, randomized data are lacking, and individual-level retrospective data are limited by selection bias. We aimed to quantify the survival impact of these therapies by analyzing how regional variation in liver therapy rates influence survival outcomes within health service areas (HSA).

The Surveillance, Epidemiology, and End Results (SEER)-Medicare database (2000-2020) was analyzed for patients aged 66-85 years with liver-isolated CRCLM who underwent curative-intent liver therapy (i.e., hepatectomy, ablation, or transplantation). Rates of resection within HSAs for each year were calculated. A comparison of observed versus expected survival was performed between two eras (era 1: 2002-2004; era 2: 2013-2015) to quantify the impact of changing rates of curative-intent liver therapy on HSA-level survival.

A total of 34,781 patients across 163 HSAs were included. Most patients had synchronous CRCLM (65.8%) and received chemotherapy (63.1%); a minority (10.9%) underwent curative-intent liver therapy (hepatectomy, 74.3%; ablation alone, 24.9%; transplantation 0.8%). A total of 56 (34%) HSAs had the rate of curative-intent liver therapy increase (≥ 5%) across eras, 58 (36%) HSAs had the rate remain constant, and 49 (30%) HSAs experienced a rate decrease (≥ 5%). Each 5% increase in the rate of curative-intent liver therapy was associated with a 1.2% (95% CI 0.4-2.0%) increase in the risk-adjusted survival rate (p = 0.003).

HSA variation in rates of curative-intent therapy for CRCLM was associated with population-level changes in survival. These data quantify the expected improvements associated with efforts to increase patient access to curative-intent therapies for CRCLM.

Percutaneous image-guided thermal ablation is an established local curative-intent treatment technique for the treatment of primary and secondary malignant liver tumors. Whereas margin assessment after surgical resection can be accomplished with microscopic examination of the resected specimen, margin assessment after percutaneous thermal ablation relies on cross-sectional imaging. The critical measure of technical success is the minimal ablative margin (MAM), defined as the minimum distance between the tumor and the edge of the ablation zone. Traditionally, the MAM has been assessed qualitatively using anatomic landmarks, which has suboptimal accuracy and reproducibility and is prone to operator bias. Consequently, specialized software-based methods have been developed to standardize and automate MAM quantification. In this review, the authors discuss the technical components of such methods, including image acquisition, segmentation, registration, and MAM computation, define the sources of measurement error, describe available software solutions in terms of image processing techniques and modes of integration, and outline the current clinical evidence, which strongly supports the use of such dedicated software. Finally, the authors discuss current logistical and financial barriers to widespread use of ablation confirmation methods as well as potential solutions. Keywords: Ablation Techniques, CT, Image Postprocessing, Liver Supplemental material is available for this article. © RSNA, 2025.

This study aimed to investigate the impact of the mutational status of multiple genes on survival in Chinese patients with colorectal liver metastases (CRLM) undergoing liver resection.

This study included 519 Chinese patients undergoing curative liver resection for CRLM between 2011 and 2021 and had genomic sequencing data of 620 genes available for analysis. The genes associated with overall survival (OS) were identified using Cox regression analyses. The patients were stratified according to a novel scoring system based on the number of genes with a deleterious status (mutation or wild type), and OS was compared among the groups. The prognostic capacity of the scoring system was assessed using Harrell's C-index.

Twelve genes were mutated in more than 10% of the patients. RAS mutation, SMAD4 mutation, and APC wild-type status were significantly associated with worse OS. A scoring system was built based on the mutational status of RAS, SMAD4, and APC. Higher scores were significantly associated with worse OS (HR > 1, p < 0.05, for any two groups), and the patients with a score of 3 had poor survival with a median OS of only 17.1 months. The scoring system demonstrated moderate discriminative capacity (Harrell's C-index = 0.627).

In Chinese patients, the mutational status of RAS, SMAD4, and APC was significantly associated with survival after CRLM resection. The three-gene scoring system provided information on prognostic stratification for survival, which can be used to improve precision surgery for CRLM.

A growing body of evidence has demonstrated the expanding role of local treatment in managing colorectal cancer liver metastases (CRCLM). To identify current research trends and forecast future directions, we conducted a bibliometric analysis to examine global collaboration patterns and academic influence across countries, institutions, journals, and authors.

Relevant articles and reviews on CRCLM local therapies were systematically retrieved from the Web of Science Core Collection. The bibliometric package in R software and VOSviewer software were used to analyze countries, institutions, journals, authors, and keywords. The research status and key areas of local treatment of colorectal cancer liver metastases were analyzed by keywords.

The analysis encompassed 2,695 articles published between 2008 and 2023. The United States emerged as the leading contributor, with Memorial Sloan Kettering Cancer Center producing the highest number of publications (n=178). Among journals, Annals of Surgical Oncology ranked first in publication volume, while Journal of Vascular and Interventional Radiology achieved the highest citation count. The local treatment modalities for CRCLM included transarterial therapies (radioembolization and chemoembolization), hepatic artery infusion chemotherapy and immunotherapy, imaging guidance methods, hepatectomy and survival, and ablation and stereotactic body radiotherapy. Recent studies highlighted ablations, microspheres, and immunotherapy as key research areas, with thematic mapping identifying immunotherapy as an emerging niche field.

CRCLM local treatment research focuses on integrating local and systemic therapies. Preclinical studies, RFA with anti - PD - 1 agents, show enhanced anti - tumor immunity and survival. While the synergy of local and immunotherapy is confirmed, large - scale clinical evidence is still needed. Thus, cross - disciplinary cooperation is urgently required to boost translational medical research.

To evaluate the applicability of the M1 category of the version-nine of AJCC/UICC TNM staging system (TNM-9) for M1 nasopharyngeal carcinoma (M1-NPC) in immunotherapy era and propose potential refinements.

M1-NPC patients who underwent palliative chemotherapy and immune checkpoint inhibitors (ICIs) between January 2019 and June 2023 across five institutions were included and re-staged according to TNM-9. Overall survival (OS) and Progression-free survival (PFS) were analyzed. A recursive partitioning analysis (RPA) model was employed to derive a new RPA-M1 category.

Among the 472 patients included, 219 were M1a and 253 were M1b. With a median follow-up time of 27 months, the M1a subgroup exhibited significantly higher 2-year OS (90.4 % vs. 73.7 %) and PFS (69.2 % vs. 40.6 %) than M1b subgroup (all P<0.001), which was further confirmed by multivariate analysis (MVA). Additionally, number of involved organs was found to be another independent predictor. New RPA-M1 category were then developed: RPA-M1a (≤3 metastatic lesions and confined to one single organ), RPA-M1b (≤3 metastatic lesions but involving multiple organs or >3 lesions and confined to one single organ), and RPA-M1c (patients with >3 metastatic lesions and involving multiple organs), with 2-year OS rates of 91.5 %, 81.4 %, and 69.8 %, respectively (P < 0.05) and PFS rates of 72.4 %, 54.3 % and 29.1 %, respectively (P < 0.005). Compared to the M1 Category in TNM-9, RPA-M1 category had a lower Akaike Information Criterion (AIC) and a higher concordance index (C-index) for OS and PFS.

The M1 category in the TNM-9 is applicable in the immunotherapy era. The RPA-M1 category offers improve depiction of survival outcomes compared to TNM-9, allowing for more refined stratification of patient outcomes and individulized decision-tailoring.

To compare early recurrence patterns, safety, survival and investigate the clinical risk factors of early recurrence (ER) after liver resection or thermal ablation (TA) for patients with colorectal liver metastases (CRLM) with number ≤ 5 and largest diameter ≤ 3 cm.

This retrospective study included patients with CRLM who underwent liver resection or TA between January 2016 and December 2021 at two hospitals in China. The Kaplan-Meier method and log-rank test were used to assess recurrence-free survival (RFS) and overall survival (OS). Risk factors for ER were analysed using univariate and multivariate Cox regression analyses.

303 patients with 632 liver metastases were enrolled. The most common early recurrence pattern was intrahepatic recurrence (IHR) in resection group and TA group. There was no significant difference in 6-month RFS rate (65.81% vs 66.23%) and median OS (P = 0.10) between two groups. Patients without ER had better OS than those with ER (P < 0.05). The incidence of serious complications (P = 0.013), length of hospitalization (P < 0.01), and albumin-bilirubin (ALBI) score (P = 0.038) in TA group were significantly better than resection group. The diameter of liver metastases (HR: 4.89, 95% CI: 1.16-20.60; P = 0.031) and clinical risk score (CRS) (HR: 1.86, 95% CI: 1.06-3.25; P = 0.029) were independent risk factors for ER.

For CRLM with largest diameter ≤ 3 cm and number ≤ 5, the efficacy of receiving resection or TA is comparable, and the safety of TA is better. TA may be considered as the first-line local treatment option for patients with CRLM.

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal cancers, with a 5-year survival rate that has improved only marginally over the past 30 years, despite numerous clinical trials. PDAC poses several unique challenges, including early metastatic spread and a predilection for liver metastasis. It is also highly resistant to anti-tumor immunity and immunotherapy due to its dense and immunosuppressive tumor microenvironment, low immunogenicity, and systemic immune suppression. PDAC has a low mutational burden, defective antigen presentation, and immune checkpoint molecule upregulation, which reduce immune recognition. Together, these factors leave PDAC as an "immune cold" tumor with minimal cytotoxic T-cell activity. Novel therapeutic approaches are urgently needed to reinvigorate anti-tumor immunity. Recent advances, such as adjuvant personalized mRNA neoantigen vaccines and mutant-KRAS targeted vaccines, have demonstrated sustained vaccine-induced T cell responses that are associated with improved recurrence-free survival in surgically resected PDAC. Combining different vaccine approaches with optimal sequencing of chemotherapy, surgery, radiotherapy, and other immunotherapies may further enhance outcomes. PDAC vaccines represent a promising strategy for overcoming PDAC's resistance to conventional therapies, with ongoing trials exploring their potential to improve long-term survival.

Stereotactic ablative radiotherapy (SABR) commonly is used for small liver metastases. Modern conformal radiotherapy techniques, including 3-dimensional conformal radiotherapy and intensity-modulated radiation therapy, enable the safe delivery of SABR to small liver volumes. For larger tumors, the safe delivery of SABR can be challenging due to a more limited volume of healthy normal liver parenchyma and the proximity of the tumor to radiosensitive organs, such as the stomach, duodenum, and large intestine. Controlling respiratory motion, the use of image guidance, and increasing the number of radiation fractions sometimes are necessary for the safe delivery of SABR in these situations.

Thermal ablation has been widely used for patients with small colorectal liver metastases (CRLMs), even for resectable cases; however, solid evidence has been scarce. (1) Thermal ablation versus liver resection. Some propensity-score matching studies using patients with balanced baseline characteristics have confirmed less invasiveness and the comparable survival benefits of thermal ablation to liver resection. A more recent pivotal randomized controlled trial comparing thermal ablation and liver resection was presented during the American Society of Clinical Oncology 2024 meeting. Diameter ≤ 3 cm, ten or fewer resectable and ablatable CRLMs were assigned to thermal ablation or liver resection. No differences were observed in the overall survival and local and distant progression-free survival with less morbidity. (2) Combination of thermal ablation and liver resection. Four matching studies demonstrated comparable data between the combination and liver resection alone groups in the long-term survival and recurrence rates without increasing the postoperative complication rates. The selection of the two approaches depends primarily on the number, size, and location of the CRLMs. (3) Chemotherapy in combination with thermal ablation. A propensity-score matching study comparing thermal ablation ± neoadjuvant chemotherapy was conducted. The addition of neoadjuvant chemotherapy was an independent predictive factor for good progression-free survival without increasing morbidity. Two randomized controlled trials demonstrated that additional thermal ablation to systemic chemotherapy can improve the overall survival for initially unresectable CRLMs. (4) Conclusions. Thermal ablation can provide survival benefits for patients with CRLMs in various situations, keeping adequate indications.

Breast cancer represents one of the most common malignancies worldwide. In early stages a combination of treatment strategies are offered with curative intent, whereas the therapeutic aim in metastatic disease is to provide the longest possible survival with an acceptable quality of life. The term "oligometastasis", first described by Hellmann and Weichselbaum in 1995, represents an intermediate state between local and systemic disease, where radical focal treatments to all metastatic lesions might have a curative potential. Due to sufficient lack of data, the proper management of oligometastatic disease remains even until today a highly unmet need. Surgery, radiotherapy or ablation (radiofrequency or cryotherapy) are among the local eradication therapies that could offer long-term outcomes in patients with oligometastatic breast cancer (OMBC). The present review aims to bring the readers up to the latest data regarding the management of OMBC according to the different organs involved by setting a framework of current treatment paradigms. It also brings to the forefront debatable questions requiring multidisciplinary approach and highlights the concerns arising from dealing with this clinically and biologically unique entity in everyday clinical practice.

The management of colorectal cancer liver metastases requires a multidisciplinary approach, which may incorporate systemic therapy, surgery, or local ablative therapies. Stereotactic body radiation therapy (SBRT) is a non-invasive highly conformal radiation technique that enables the delivery of large doses of radiation in a few fractions to well-defined targets using image-guidance and motion management. For selected patients with colorectal cancer liver metastases, stereotactic body radiation therapy can be delivered safely, with excellent long-term local control and overall survival. The purpose of this clinical practice review is to review the background, indications, and treatment details of stereotactic body radiation therapy for the treatment of colorectal liver metastases. SBRT for colorectal cancer liver metastases may be considered for patients with oligometastatic colorectal cancer in combination with surgery or other locally ablative therapies; for patients who are not candidates for surgical resection; or after failure of resection or other ablative therapies. When planning SBRT both a computed tomography and magnetic resonance imaging simulation may be obtained, where feasible, for target delineation. One or 3 fraction SBRT can be considered for lesions away from the central liver and luminal organs at risk, whereas 5 fraction SBRT is preferred otherwise. Image-guidance and motion management strategies are essential components of liver SBRT and will guide the creation of relevant internal and planning target volume margins. For lesions in close proximity to or overlapping with organs-at-risk, the balance between adequate local control and potential for cure with potential acute and late toxicity must be carefully considered.

The study explores the role of liver debulking surgery in cases of unresectable colorectal liver metastases (CRLM), challenging the traditional notion that surgery is not a valid option in such scenarios.

Patients with advanced but resectable disease who underwent surgery with a curative intent (Group I) and those with advanced incompletely resectable disease who underwent a "debulking" hepatectomy (Group II) were compared.

There was no difference in the intra-operative and post-operative results between the two groups. The 3-year and 5-year OS rates were 69% and 47% for group 1 vs 64% and 35% for group 2 respectively (p = 0.14). The 3-year and 5-year PFS rates were 32% and 21% for group 1 vs 12% and 8% for group 2 respectively (p = 0.009). Independent predictors of PFS in the debulking group were bilobar metastases (HR = 2.70; p = 0.02); the presence of extrahepatic metastasis (HR = 2.65, p = 0.03) and the presence of more than 9 metastases (HR = 2.37; p = 0.04). Iterative liver surgery for CRLM was a significant protective factor (HR = 0.34, p = 0.04).

An aggressive palliative surgical approach may offer a survival benefit for selected patients with unresectable CRLM, without increasing the morbidity. The decision for surgery should be made on a case-by-case basis.

Metastatic colorectal cancer (mCRC) is a major cause of cancer-related death, with a 5-year relative overall survival of up to 20%. The liver is the most common site of distant metastasis in colorectal cancer (CRC), with about 50% of CRC patients metastasizing to their liver over the course of their disease. Complete liver resection is the primary modality of treatment for resectable colorectal cancer liver metastasis (CRLM), with an overall 5-year survival rate of up to 58%. However, only 15% to 20% of patients with CRLM are deemed suitable for resection at presentation. For unresectable diseases, the median survival of patients remains low even with the best chemotherapy. In recent decades, the management of CRLM has continued to evolve with the expansion of resection criteria, novel targeted systemic therapies, and improved locoregional therapies. However, due to the heterogeneity of the CRC patient population, the optimal evaluation of treatment options for CRLM remains complex. Therefore, effective management requires a multidisciplinary team to help define resectability and devise a personalized treatment approach, from the initial diagnosis to the final treatment.

Background: Evidence comparing the efficacy of different treatments for patients with unresectable colorectal liver metastases (CRLM) receiving first-line or maintenance therapy is sparse. We aimed to assess the efficacy and safety of these treatments, with a distinct focus on evaluating first-line and maintenance treatments separately. Methods: We conducted Bayesian network meta-analyses, sourcing English-language randomized controlled trials (RCTs) published through July 2023 from databases including PubMed, Embase, the Cochrane Library, ClinicalTrials.gov, and key conference proceedings. Phase Ⅱ or Ⅲ trials that assessed two or more therapeutic regimens were included. Primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), objective response rate (ORR), adverse events graded as 3 or above (SAE), and R0 liver resection rate. Hazards Ratios (HRs) and 95% confidence intervals (CI) were used as effect size for OS and PFS, Odds Ratios (ORs) and 95% CI were used for ORR, SAEs and R0 resection rate. Subgroup and sensitive analyses were conducted to analysis the model uncertainty (PROSPERO: CRD42023420498). Results: 56 RCTs were included (50 for first-line treatment, six for maintenance therapies), with a total of 21,323 patients. Regarding first-line, for OS, the top three mechanisms were: local treatment + single-drug chemotherapy (SingleCT), Targeted therapy (TAR)+SingleCT, and TAR + multi-drug chemotherapy (MultiCT). Resection or ablation (R/A)+SingleCT, S1, and Cetuximab + intensified fluorouracil-based combination chemotherapy (ICTFU) were identified as the best treatments. For PFS, the top three mechanisms were: Immune therapy + TAR + MultiCT, multi-targeted therapy (MultiTAR), TAR + SingleCT. The top three treatments were: Atezolizumab + Bevacizumab + fluorouracil-based combination chemotherapy (CTFU), TAS-102+bevacizumab, Bevacizumab + ICTFU. Cetuximab + CTFU was the best choice for RAS/RAF wild-type patients. Regarding maintenance treatment, Bevacizumab + SingleCT and Adavosertib were the best options for OS and PFS, respectively. For safety, MultiCT was the safest, followed by local treatment + MultiCT, TAR + MultiCT caused the most SAEs. Bevacizumab plus chemotherapy was found to be the safest among all targeted combination therapies. Conclusion: In first-line, local treatment or targeted therapsy plus chemotherapy are the best mechanisms. R/A + SingleCT or CTFU performed the best for OS, Atezolizumab + Bevacizumab + ICTFU was the best option regarding PFS. For RAS/RAF wild-type patients, Cetuximab + CTFU was the optimal option. Monotherapy may be preferred choice for maintenance treatment. Combination therapy resulted in more SAEs when compared to standard chemotherapy.

There is increasing interest in the efficacy of stereotactic ablative radiotherapy (SABR) for treating colorectal cancer (CRC) patients with oligometastases (OM), recently. The purpose of this meta-analysis was to evaluate local control (LC), progression-free survival (PFS), and overall survival (OS) of CRC patients with pulmonary OM treated with SABR and toxicities.

Studies that reported SABR for CRC patients with pulmonary OM were searched from MEDLINE and Embase. Treatment outcomes including LC, PFS, OS, and toxicities of grade 3 or higher were assessed.

A total of 19 studies with 1,668 patients were chosen for this meta-analysis. Pooled 1-, 2-, and 3-year LC rates were 83.1%, 69.3%, and 63.9%, respectively. PFS rates were 44.8%, 26.5%, and 21.5% at 1, 2, and 3 years, respectively. OS rates at 1-, 2-, and 3-year were 87.5%, 69.9%, and 60.5%, respectively. The toxicity rate of grade 3 or higher was 3.6%. The effect of dose escalation was meta-analyzed using available studies.

Application of SABR to CRC patients with pulmonary OM achieved modest local control with acceptable toxicity according to the present meta-analysis. Further studies establishing the clinical efficacy of SABR are guaranteed.

By presenting the most up-to-date findings and incorporating the latest evidence, this article seeks to present a comprehensive guide for navigating the complexities inherent in the management of colorectal liver metastasis. It aims to serve as a valuable resource offering clinicians and healthcare professionals an understanding of the diverse modalities and approaches available for treating this challenging and multifaceted disease. In an era of rapidly evolving medical knowledge, this article examines the latest insights to make informed decisions in the realm of colorectal liver metastasis management. The article does not only highlight the up-to-date knowledge but also provides the evidence for existing therapeutic strategies. This practical tool provides evidence-based recommendations to clinicians, thereby contributing to the ongoing advancement of effective treatment strategies for this challenging disease.

Stereotactic ablative radiotherapy (SABR) can extend survival and offers the potential for cure in some patients with oligometastatic disease (OMD). However, limited evidence exists regarding its use in oligometastatic hepatocellular carcinoma (HCC). We aimed to prospectively investigate the efficacy and safety of SABR in patients with oligometastatic HCC.

We enrolled patients with controlled primary HCC and one to five metastatic lesions amenable to SABR. The primary endpoint was treatment efficacy defined as overall survival (OS) and progression-free survival (PFS). The secondary endpoints included time to local progression, objective response rate, disease control rate, toxicities, and quality of life (QOL), assessed using the EORTC QLQ-C30 before, and 0, 1, and 3 months after SABR.

Overall, 40 consecutive patients received SABR on 62 lesions between 2021 and 2022. The most common locations for OMD were the lungs (48.4%), lymph nodes (22.6%), and bone (17.7%). After a median follow-up of 15.5 months, the 2-year OS was 80%. Median PFS was 5.3 months, with 1- and 2-year PFS rates of 21.2% and 0%, respectively. A shorter time to OMD from the controlled primary independently correlated with PFS (p = 0.039, hazard ratio 2.127) alongside age, Child-Pugh class, and alpha-fetoprotein (p = 0.002, 0.004, 0.019, respectively). The 2-year time to local progression, objective response rate, and disease control rate were 91.1%, 75.8%, and 98.4%, respectively. Overall, 10% of patients experienced acute toxicity, and 7.5% experienced late toxicity, with no grade 3+ toxicity. All QOL scores remained stable, whereas the patients without systemic treatments had improved insomnia and social functioning scores.

SABR is an effective and feasible option for oligometastatic HCC that leads to excellent local tumor control and improves survival without adversely affecting QOL.

Stereotactic ablative radiotherapy (SABR) is a non-invasive treatment approach capable of efficiently ablating the target lesion; however, neither the oligometastatic disease concept nor the potential benefits of SABR have been well-defined in hepatocellular carcinoma (HCC). According to this study, SABR is an effective and safe treatment option for oligometastatic HCC, yielding excellent local tumor control and survival improvement without worsening patients' quality of life, regardless of tumor sites. We also demonstrated that patients with a later presentation of OMD from the controlled primary and lower alpha-fetoprotein levels achieved better survival outcomes. This is the first prospective study of SABR in oligometastatic HCC, providing insights for the development of novel strategies to improve oncologic outcomes.

NCT05173610.

Thermal ablation is routinely used for solitary colorectal liver metastases (SCLM), but the added value of adjuvant systemic therapy in SCLM remains unclear. This study aimed to compare the long-term outcomes for SCLM treated by ablation alone (AB) versus ablation plus systemic therapy (AS).

This multicenter retrospective study using nationwide data from fourteen institutions between October 2010 and May 2023, 369 patients with initial SCLM smaller than 5 cm, no extrahepatic metastases, and colorectal cancer R0 resection treated by thermal ablation were included. The crude analysis was used to analyze eligible cases between the two groups. The propensity score matching to control for potential confounders in each matched group. Subgroup analyses were performed to identify specific survival benefits.

61.2% (226/369) of eligible patients were treated with AS and 38.8% (143/369) with AB. During the median follow-up period of 8.8 years, 1-/3-/5-year DFS/OS rates did not differ between the two groups, when analyzed via propensity score matching ( P =0.52/0.08). Subgroup analysis revealed that AS was significantly associated with better OS than AB in patients with plasma CEA >5 ug/l ( P =0.036), T (III-IV) category of primary cancer ( P =0.034), or clinical risk score (1-2) ( P =0.041). In each matched group, the authors did find a significant difference in drug-related adverse events ( P <0.001) between AS group (24.1%, 28/116) and AB group (0.0%, 0/116).

For patients with plasma CEA >5 ug/l, T (III-IV) category of primary cancer, or clinical risk score (1-2), thermal ablation plus systemic therapy appeared to be associated with improved overall survival. Thermal ablation was equally effective in disease-free survival for treating SCLM, whether with or without adjuvant systemic therapy.

Optimal dose and fractionation in stereotactic body radiotherapy (SBRT) for oligometastatic cancer patients remain unknown. In this interim analysis of OligoCare, we analyzed factors associated with SBRT dose and fractionation.

Analysis was based on the first 1,099 registered patients. SBRT doses were converted to biological effective doses (BED) using α/β of 10 Gy for all primaries, and cancer-specific α/β of 10 Gy for non-small cell lung and colorectal cancer (NSCLC, CRC), 2.5 Gy for breast cancer (BC), or 1.5 Gy for prostate cancer (PC).

Of the interim analysis population of 1,099 patients, 999 (99.5 %) fulfilled inclusion criteria and received metastasis-directed SBRT for NSCLC (n = 195; 19.5 %), BC (n = 163; 16.3 %), CRC (n = 184; 18.4 %), or PC (n = 457; 47.5 %). Two thirds of patients were treated for single metastasis. Median number of fractions was 5 (IQR, 3-5) and median dose per fraction was 9.7 (IQR, 7.7-12.4) Gy. The most frequently treated sites were non-vertebral bone (22.8 %), lung (21.0 %), and distant lymph node metastases (19.0 %). On multivariate analysis, the dose varied significantly for primary cancer type (BC: 237.3 Gy BED, PC 300.6 Gy BED, and CRC 84.3 Gy BED), and metastatic sites, with higher doses for lung and liver lesions.

This real-world analysis suggests that SBRT doses are adjusted to the primary cancers and oligometastasis location. Future analysis will address safety and efficacy of this site- and disease-adapted SBRT fractionation approach (NCT03818503).

A survey of medical oncologists (MOs), radiation oncologists (ROs), and surgical oncologists (SOs) who are experts in the management of patients with metastatic colorectal cancer (mCRC) was conducted to identify factors used to consider metastasis-directed therapy (MDT).

An online survey to assess clinical factors when weighing MDT in patients with mCRC was developed based on systematic review of the literature and integrated with clinical vignettes. Supporting evidence from the systematic review was included to aid in answering questions.

Among 75 experts on mCRC invited, 47 (response rate 62.7%) chose to participate including 16 MOs, 16 ROs, and 15 SOs. Most experts would not consider MDT in patients with 3 lesions in both the liver and lung regardless of distribution or timing of metastatic disease diagnosis (6 vs. 36 months after definitive treatment). Similarly, for patients with retroperitoneal lymph node and lung and liver involvement, most experts would not offer MDT regardless of timing of metastatic disease diagnosis. In general, SOs were willing to consider MDT in patients with more advanced disease, ROs were more willing to offer treatment regardless of metastatic site location, and MOs were the least likely to consider MDT.

Among experts caring for patients with mCRC, significant variation was noted among MOs, ROs, and SOs in the distribution and volume of metastatic disease for which MDT would be considered. This variability highlights differing opinions on management of these patients and underscores the need for well-designed prospective randomized trials to characterize the risks and potential benefits of MDT.

The aim of this article is to provide an overview on the most frequently applied image-guided, percutaneous, local ablative techniques for treatment of primary and secondary liver tumors. The technical procedures of microwave ablation (MWA) and radiofrequency ablation (RFA) are presented. The pre-interventional diagnostics, indications and feasibility are also discussed, taking the current national guidelines into consideration. Finally, treatment outcomes and recommendations on post-interventional imaging following local tumor ablation are presented.

The evolving role of stereotactic ablative radiation therapy (SABR) as metastasis-directed therapy (MDT) for oligometastatic prostate cancer (omPCa) will be discussed.

Oligometastatic disease (OMD) is an intermediate state between localized and wide-spread malignant disease. OMD has recently been spotlighted given the increasing demonstration of clinical benefit from local therapies despite presence of metastatic disease and allure of the curative potential of MDT in select cases. Among the different forms of MDT, SABR has rapidly become a widely adopted treatment modality. Significant efforts in this space have focused on omPCa, owing to its relatively indolent biology, presence of a sensitive and specific serum biomarker and recent advances in molecular imaging. While most studies have evaluated the role of SABR MDT in hormone sensitive omPCa, new emerging clinical data also suggests benefits of SABR MDT for even castration-resistant disease.

Treating omPCa with SABR MDT appears to generate an efficacy signal with minimal morbidity across both hormone-sensitive and castration-resistant disease. However, additional definitive omPCa trial data are needed. Future research efforts should investigate biomarkers for this heterogeneous disease space and the role of SABR MDT in combination with systemic agents to improve upon standard of care treatments.

For patients with liver-confined metastatic colorectal cancer (mCRC), local therapy of isolated metastases has been associated with long-term progression-free and overall survival (OS). However, for patients with more advanced mCRC, including those with extrahepatic disease, the efficacy of local therapy is less clear although increasingly being used in clinical practice. Prospective studies to clarify the role of metastatic-directed therapies in patients with mCRC are needed.

The Evaluating Radiation, Ablation, and Surgery (ERASur) A022101/NRG-GI009 trial is a randomized, National Cancer Institute-sponsored phase III study evaluating if the addition of metastatic-directed therapy to standard of care systemic therapy improves OS in patients with newly diagnosed limited mCRC. Eligible patients require a pathologic diagnosis of CRC, have BRAF wild-type and microsatellite stable disease, and have 4 or fewer sites of metastatic disease identified on baseline imaging. Liver-only metastatic disease is not permitted. All metastatic lesions must be amenable to total ablative therapy (TAT), which includes surgical resection, microwave ablation, and/or stereotactic ablative body radiotherapy (SABR) with SABR required for at least one lesion. Patients without overt disease progression after 16-26 weeks of first-line systemic therapy will be randomized 1:1 to continuation of systemic therapy with or without TAT. The trial activated through the Cancer Trials Support Unit on January 10, 2023. The primary endpoint is OS. Secondary endpoints include event-free survival, adverse events profile, and time to local recurrence with exploratory biomarker analyses. This study requires a total of 346 evaluable patients to provide 80% power with a one-sided alpha of 0.05 to detect an improvement in OS from a median of 26 months in the control arm to 37 months in the experimental arm with a hazard ratio of 0.7. The trial uses a group sequential design with two interim analyses for futility.

The ERASur trial employs a pragmatic interventional design to test the efficacy and safety of adding multimodality TAT to standard of care systemic therapy in patients with limited mCRC.

ClinicalTrials.gov: NCT05673148, registered December 21, 2022.

Liver is the most common site of colorectal cancer (CRC) metastases. Treatment of CRC liver metastases (CRLM) includes different strategies, prevalently based on the clinical and oncological intent. Valid approaches in liver-limited or liver-prevalent disease include surgery, percutaneous ablative procedures (radiofrequency ablation, microwave ablation), intra-arterial perfusional techniques (chemo-embolization, radio-embolization) as well as stereotactic radiotherapy. Systemic treatments, including chemotherapy, immunotherapy and other biological agents, are the only options for patients with no chance of locoregional approaches. The use of chemotherapy in other settings, such as neoadjuvant, adjuvant or conversion therapy of CRLM, is commonly accepted in the clinical practice, although data from several clinical trials have been mostly inconclusive. The optimal integration of all these strategies, when applicable and clinically indicated, should be ever considered in patients affected by CRLM based on clinical evidence and multidisciplinary experience. Here we revised in detail all the possible therapeutic approaches of CRLM focusing on the current evidences, the studies still in progress and the often contradictory data.

Colorectal cancer (CRC) is one of the most common tumours worldwide, and 70% of CRC patients are over 65 years of age. However, the scientific evidence available for these patients is poor, as they are underrepresented in clinical trials. Therefore, a group of experts from the Oncogeriatrics Section of the Spanish Society of Medical Oncology (SEOM), the Spanish Cooperative Group for the Treatment of Digestive Tumours, (TTD) and the Multidisciplinary Spanish Group of Digestive Cancer (GEMCAD) have reviewed the scientific evidence available in older patients with CRC. This group of experts recommends a multidisciplinary approach and geriatric assessment (GA) before making a therapeutic decision because GA predicts the risk of toxicity and survival and helps to individualize treatment. In addition, elderly patients with localized CRC should undergo standard cancer resection, preferably laparoscopically. The indication for adjuvant chemotherapy (CT) should be considered based on the potential benefit, the risk of recurrence, the life expectancy and patient comorbidities. When the disease is metastatic, the possibility of radical treatment with surgery, radiofrequency (RF) or stereotactic body radiation therapy (SBRT) should be considered. The efficacy of palliative CT is similar to that seen in younger patients, but elderly patients are at increased risk of toxicity. Clinical trials should be conducted with the elderly population and include GAs and specific treatment plans.

The objective of this study is to establish and validate a radiomics nomogram for prediction of local tumor progression (LTP) after microwave ablation (MWA) for recurrent colorectal liver metastases (CRLM) after hepatic resection. We included 318 consecutive recurrent CRLM patients (216 of training while 102 of validation cohort) with contrast-enhanced computerized tomography images treated with MWA between January 2014 and October 2018. Support vector machine-generated radiomics signature was incorporated together with clinical information to establish a radiomics nomogram. Our constructed radiomics signature including 15 features (first-order intensity statistics features, shape and size-based features, gray level size zone/dependence matrix features) performed well in assessing LTP for both cohorts. With regard to its predictive performance, its C-index was 0.912, compared to the clinical or radiomics models only (c-statistic 0.89 and 0.75, respectively) in the training cohort. In the validation cohort, the radiomics nomogram had better performance (area under the curve = 0.89) compared to the radiomics and clinical models (0.85 and 0.69). According to decision curve analysis, our as-constructed radiomics nomogram showed high clinical utility. As revealed by survival analysis, LTP showed worse progression-free survival (3-year progression-free survival 42.6% vs 78.4%, P < .01). High-risk patients identified using this radiomics signature exhibited worse LTP compared with low-risk patients (3-year LTP 80.2% vs 48.6%, P < .01). A radiomics-based nomogram of pre-ablation computerized tomography imaging may be the precious biomarker model for predicting LTP and personalized risk stratification for recurrent CRLM after hepatic resection treated by MWA.

For patients with liver-confined metastatic colorectal cancer (mCRC), local therapy of isolated metastases has been associated with long-term progression-free and overall survival (OS). However, for patients with more advanced mCRC, including those with extrahepatic disease, the efficacy of local therapy is less clear although increasingly being used in clinical practice. Prospective studies to clarify the role of metastatic-directed therapies in patients with mCRC are needed.

The Evaluating Radiation, Ablation, and Surgery (ERASur) A022101/NRG-GI009 trial is a randomized, National Cancer Institute-sponsored phase III study evaluating if the addition of metastatic-directed therapy to standard of care systemic therapy improves OS in patients with newly diagnosed limited mCRC. Eligible patients require a pathologic diagnosis of CRC, have BRAF wild-type and microsatellite stable disease, and have 4 or fewer sites of metastatic disease identified on baseline imaging. Liver-only metastatic disease is not permitted. All metastatic lesions must be amenable to total ablative therapy (TAT), which includes surgical resection, microwave ablation, and/or stereotactic ablative body radiotherapy (SABR) with SABR required for at least one lesion. Patients without overt disease progression after 16-26 weeks of first-line systemic therapy will be randomized 1:1 to continuation of systemic therapy with or without TAT. The trial activated through the Cancer Trials Support Unit on January 10, 2023. The primary endpoint is OS. Secondary endpoints include event-free survival, adverse events profile, and time to local recurrence with exploratory biomarker analyses. This study requires a total of 346 evaluable patients to provide 80% power with a one-sided alpha of 0.05 to detect an improvement in OS from a median of 26 months in the control arm to 37 months in the experimental arm with a hazard ratio of 0.7. The trial uses a group sequential design with two interim analyses for futility.

The ERASur trial employs a pragmatic interventional design to test the efficacy and safety of adding multimodality TAT to standard of care systemic therapy in patients with limited mCRC.

Nearly one-third of patients diagnosed with colorectal cancer (CRC) will ultimately develop metastatic disease. While a small percentage of patients can be considered for curative resection, more patients have limited disease that can be considered for local therapy. Challenges remain in defining oligometastatic CRC as well as developing treatment strategies guided by high level evidence.

In this review, we present the challenges in defining oligometastatic CRC and summarize the current literature on treatment and outcomes of local therapy in patients with metastatic CRC.

For patients with liver- and/or lung-confined CRC metastases, surgical resection is the standard of care given the potential for long-term progression-free and overall survival. For patients with liver- or lung-confined disease not amenable to surgical resection, non-surgical local therapies, such as thermal ablation, hepatic arterial infusion pump (HAIP), or stereotactic body radiation therapy (SBRT), should be considered. For patients with more advanced disease, such as lymph node or bony metastases, the role of metastasis-directed therapy is controversial. Emerging data suggests that SBRT to ablate all metastases can improve progression-free and overall survival.

Multidisciplinary management is critical for patients with metastatic CRC due to the complexity of their cases and the nuanced patient, tumor, biological, and anatomical factors that must be weighed when considering local therapy. High-quality prospective randomized data in CRC are needed to further clarify the role of local ablative therapy in patients with unresectable oligometastatic CRC with ongoing studies including the RESOLUTE trial (ACTRN12621001198819) and the upcoming NCTN ERASur trial (NCT05673148).

For patients with initially unresectable colorectal liver metastasis (IU-CRLM) receiving conversion therapy, disease relapse after conversion hepatectomy is common. However, few studies have focused on the assessment and management of relapse following conversion hepatectomy for IU-CRLM.

In the retrospective cohort study, 255 patients with IU-CRLM received conversion therapy and underwent subsequent R0 resection. The treatment effects of repeated liver-directed treatment (RLDT) versus non-RLDT for liver relapse were examined. Survival analysis was evaluated with the use of Cox proportional hazards methods. The importance of RLDT was further confirmed in the propensity score matching (PSM) and subgroup analyses.

The 5-year overall survival (OS) rate after conversion hepatectomy was 34.9%. Liver relapse was observed in 208 patients. Of these patients, 106 underwent RLDT (65 underwent repeated hepatectomy and the remainder underwent ablation treatment), while 102 received only palliative chemotherapy. The relapse patients who underwent RLDT had a significantly longer OS than those who did not (hazard ratio (HR): 0.382, 95% CI: 0.259-0.563; P<0.001). In a multivariable analysis, RLDT was independently associated to prolonged survival (HR: 0.309, 95%CI: 0.181-0.529; P<0.001). In the PSM and subgroup analyses, RLDT consistently showed evidence of prolonging OS significantly.

For IU-CRLM patients with liver relapse following conversion hepatectomy, the RLDT is essential for cure and prolonged survival. To avoid missing the opportunity for RLDT, intensive disease surveillance should be proposed.

Unresectable colorectal cancer liver metastasis (CRLM) remains a challenging obstacle that often prevents curative treatment. In this study, we retrospectively analyzed the efficacy and safety of high-intensity focused ultrasound (HIFU) as a local adjuvant therapy for systemic chemotherapy for patients with unresectable CRLM. HIFU is a noninvasive method previously demonstrated as efficacious for various solid malignancies.

Propensity score matching was used for the combination therapy group (HIFU group, n = 59) and the observation group receiving systemic therapy only (No-HIFU group, n = 59). In addition, the survival benefit, adverse effects, and factors affecting prognosis following HIFU were evaluated.

The disease control rate was 77.9% and 62.7%, and the objective remission rate was 18.9% and 6.8% in the HIFU and non-HIFU groups, respectively. The survival analysis showed that median progression-free survival (mPFS) was 12.0 months and 11.0 months for the HIFU and non-HIFU groups, respectively (p = 0.002). The univariate and multivariate analysis showed that pre-treatment colorectal cancer liver metastasis lesion size was significantly associated with mPFS. In addition, patients that received a combination treatment for CRLM lesions <5.0 cm had a longer mPFS when compared to those receiving systemic therapy alone (13.0 months vs. 11.0 months, p = 0.001). In the HIFU group, patients with lesions <5.0 cm had a longer mPFS than patients with lesions ≥5.0 cm (13.0 months vs. 10.0 months, p = 0.04) (Figure 3B,C). Most treatment-related adverse events observed in both groups were grade 1-2. Only four cases (6.8%) of grade 1-2 skin burns were observed in patients in the HIFU group; no other statistically significant adverse events were observed.

Our study showed that HIFU ablation targeting unresectable CRLM alongside systemic therapy safely and significantly improved local control rates and prolonged mPFS, especially for lesions smaller than 5.0 cm.

The presence of hepatic metastases indicates advanced disease and is associated with significant morbidity and mortality, especially when the hepatic disease is not amenable to locoregional treatments. The primary tumour of origin, the distribution and extent of metastatic disease, the underlying liver reserve, the patient performance status and the presence of comorbidities are factors that determine whether a patient will benefit from hepatectomy or local curative-intent treatments. For patients with metastatic colorectal cancer, the most common primary cancer that spreads to the liver, several studies have demonstrated a survival benefit for patients who can be treated with hepatectomy and/or percutaneous ablation, compared to those treated with chemotherapy alone. Despite advances in surgical techniques increasing the percentage of patients eligible for surgery, most patients have unresectable disease or are poor surgical candidates. Percutaneous ablation can be used to provide local disease control and prolong survival for both surgical and non-surgical candidates. This is typically offered to patients with small hepatic metastases that can be ablated with optimal (≥10 mm) or at least adequate minimum ablation margins (≥5 mm), as high local tumour control rates can be achieved for these patients which are comparable to surgical resection. This review summarizes available evidence and outcomes following percutaneous ablation of the most frequently encountered types of hepatic metastases in the clinical practice of interventional oncology. Patient selection, technical considerations, follow-up protocols and oncologic outcomes are presented and discussed.

In the past several decades, major advances in both systemic and locoregional therapies have been made for many cancer patients. This has led to modern cancer treatment algorithms frequently calling for active interventions by multiple subspecialists at the same time. One of the areas where this can be clearly seen is the concomitant use of locoregional and systemic therapies in patients with primary or secondary cancers of the liver. These combined algorithms have gained favor over the last decade and are largely focused on the allure of the combined ability to control systemic disease while at the same time addressing refractory/resistant clonal populations. While the general concept has gained favor and is likely to only increase in popularity with the continued establishment of viable immunotherapy treatments, for many patients questions remain. Lingering concerns over the increase in toxicity when combining treatment methods, patient selection, and sequencing remain for multiple cancer patient populations. While further work remains, some of these questions have been addressed in the literature. This article reviews the available data on three commonly treated primary and secondary cancers of the liver, namely, hepatocellular carcinoma, cholangiocarcinoma, and metastatic colorectal cancer. Furthermore, strengths and weaknesses are reviewed and future directions are discussed.