Comparable long­term survival outcomes of endoscopic treatment versus surgical treatment for gastrointestinal stromal tumors with a diameter of 5-10 cm.

Currently, endoscopic treatment for small gastrointestinal stromal tumors (GIST) has been widely accepted. However, for tumors larger than 5 cm, endoscopic treatment has not been recognized by national guidelines as the standard therapy due to concerns about safety and adverse tumor outcomes. Therefore, this study compares the long-term survival outcomes of endoscopic treatment and surgical treatment for GIST in the range of 5-10 cm. We selected patients with GIST from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015. Kaplan-Meier analysis and the log-rank test were employed to compare the long-term survival outcomes between endoscopic treatment and surgical treatment. A multivariate Cox proportional hazards model was used for analysis to identify risk factors influencing patient prognosis. To balance baseline data, we performed 1:1 propensity score matching (PSM). A total of 1223 GIST patients were included, with 144 patients (11.8%) received endoscopic treatment and 1079 patients (88.2%) received surgical treatment. Before PSM, there was no significant difference in the long-term survival rates between the two groups [5-year OS (86.5% vs. 83.5%, P = 0.42), 10-year OS (70.4% vs. 66.7%, P = 0.42)]. After adjusting for covariates, we found that the overall survival (HR = 1.26, 95% CI 0.89-1.77, P = 0.19) and cancer-specific survival (HR = 1.69, 95% CI 0.99-2.89, P = 0.053) risks were comparable between the endoscopic treatment group and the surgical treatment group. In the analysis after PSM, there was no significant difference between the endoscopic treatment group and the surgical treatment group. Our study found that for GIST patients with tumor sizes between 5 and 10 cm, the long-term OS and CSS outcomes were similar between the endoscopic treatment group and the surgical treatment group.

Robot-assisted distal gastrectomy and local resection for gastric cancer and gastrointestinal stromal tumor.

Gastrointestinal stromal tumors surrounding the esophagogastric junction are often challenging to resect, with no consensus regarding the optimal surgical technique. Here in, we present a case of concurrent gastric cancer in the antrum and gastrointestinal stromal tumors adjacent to the esophagogastric junction. The patient underwent simultaneous distal gastrectomy and local resection assisted by a surgical robot, avoiding the need for total gastrectomy. The utilization of robot-assisted surgery has become an increasingly popular technique, holding promise for simplifying complex surgical procedures across diverse medical settings.

The correlation of sarcopenia and adverse events of imatinib therapy postoperatively in gastrointestinal stromal tumor through computed tomography quantitative body composition.

PURPOSE: This study aimed to investigate the correlation between sarcopenia and adverse events (AEs) of postoperative imatinib therapy through computed tomography (CT) quantitative body composition for intermediate- and high-risk gastrointestinal stromal tumors (GISTs). METHODS: The study retrospectively analyzed the clinical data of 208 patients with intermediate- and high-risk GIST treated surgically and treated with imatinib afterward at the First Affiliated Hospital of Wenzhou Medical University between October 2011 and October 2021. Images of preoperative CT scans within 1 month were used to determine the body composition of the patients. On the basis of the L3 skeletal muscle index, patients were classified into sarcopenia and nonsarcopenia groups. In 2 groups, AEs related to imatinib were analyzed. RESULTS: The proportion of AEs related to imatinib in the sarcopenia group was higher, and this disparity had a significant statistical significance (P = .013). Sarcopenia was significantly associated with hemoglobin reduction compared with nonsarcopenia (P = .015). There was a significant difference between the sarcopenia group and the nonsarcopenia group in the ratio of severe AEs (grades 3-4). Hemoglobin content (odds ratio [OR], 0.981; 95% CI, 0.963-1.000; P = .045), sex (OR, 0.416; 95% CI, 0.192-0.904; P = .027), and sarcopenia (OR, 5.631; 95% CI, 2.262-14.014; P < .001) were the influential factors of imatinib severe AEs in patients with intermediate- and high-risk GIST within 1 year after imatinib treatment. CONCLUSION: Patients with preoperative sarcopenia have a higher incidence and severity of AEs during adjuvant imatinib therapy.

The GIST of it all: management of gastrointestinal stromal tumors (GIST) from the first steps to tailored therapy. A bibliometric analysis.

PURPOSE: Improvement of patient care is associated with increasing publication numbers in biomedical research. However, such increasing numbers of publications make it challenging for physicians and scientists to screen and process the literature of their respective fields. In this study, we present a comprehensive bibliometric analysis of the evolution of gastrointestinal stromal tumor (GIST) research, analyzing the current state of the field and identifying key open questions going beyond the recent advantages for future studies to assess. METHODS: Using the Web of Science Core Collection, 5040 GIST-associated publications in the years 1984-2022 were identified and analyzed regarding key bibliometric variables using the Bibliometrix R package and VOSviewer software. RESULTS: GIST-associated publication numbers substantially increased over time, accentuated from year 2000 onwards, and being characterized by multinational collaborations. The main topic clusters comprise surgical management, tyrosine kinase inhibitor (TKI) development/treatment, diagnostic workup, and molecular pathophysiology. Within all main topic clusters, a significant progress is reflected by the literature over the years. This progress ranges from conventional open surgical techniques over minimally invasive, including robotic and endoscopic, resection techniques to increasing identification of specific functional genetic aberrations sensitizing for newly developed TKIs being extensively investigated in clinical studies and implemented in GIST treatment guidelines. However, especially in locally advanced, recurrent, and metastatic disease stages, surgery-related questions and certain specific questions concerning (further-line) TKI treatment resistance were infrequently addressed. CONCLUSION: Increasing GIST-related publication numbers reflect a continuous progress in the major topic clusters of the GIST research field. Especially in advanced disease stages, questions related to the interplay between surgical approaches and TKI treatment sensitivity should be addressed in future studies.

Convolutional neural network applied to preoperative venous-phase CT images predicts risk category in patients with gastric gastrointestinal stromal tumors.

OBJECTIVE: The risk category of gastric gastrointestinal stromal tumors (GISTs) are closely related to the surgical method, the scope of resection, and the need for preoperative chemotherapy. We aimed to develop and validate convolutional neural network (CNN) models based on preoperative venous-phase CT images to predict the risk category of gastric GISTs. METHOD: A total of 425 patients pathologically diagnosed with gastric GISTs at the authors' medical centers between January 2012 and July 2021 were split into a training set (154, 84, and 59 with very low/low, intermediate, and high-risk, respectively) and a validation set (67, 35, and 26, respectively). Three CNN models were constructed by obtaining the upper and lower 1, 4, and 7 layers of the maximum tumour mask slice based on venous-phase CT Images and models of CNN_layer3, CNN_layer9, and CNN_layer15 established, respectively. The area under the receiver operating characteristics curve (AUROC) and the Obuchowski index were calculated to compare the diagnostic performance of the CNN models. RESULTS: In the validation set, CNN_layer3, CNN_layer9, and CNN_layer15 had AUROCs of 0.89, 0.90, and 0.90, respectively, for low-risk gastric GISTs; 0.82, 0.83, and 0.83 for intermediate-risk gastric GISTs; and 0.86, 0.86, and 0.85 for high-risk gastric GISTs. In the validation dataset, CNN_layer3 (Obuchowski index, 0.871) provided similar performance than CNN_layer9 and CNN_layer15 (Obuchowski index, 0.875 and 0.873, respectively) in prediction of the gastric GIST risk category (All P >.05). CONCLUSIONS: The CNN based on preoperative venous-phase CT images showed good performance for predicting the risk category of gastric GISTs.

Clinical characteristics and prognostic analysis of postoperative recurrence or metastasis of low-risk gastrointestinal stromal tumors.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the digestive tract. This study aimed to investigate the clinical characteristics and prognosis of postoperative recurrence or metastasis in patients with low-risk stromal tumors, in order to take individualized postoperative management and treatment for patients with low-risk GISTs with relatively high recurrence. METHODS: We retrospectively analyzed the clinicopathological and follow-up data of patients with GISTs who underwent surgical resection in Nanjing Drum Tower Hospital from March 2010 to December 2021. A total of 282 patients with low-risk GISTs were included, none of whom were treated with imatinib. Univariate and multivariate Cox analysis and survival curves were used to explore the relationship between clinical features and recurrence or metastasis in patients with low-risk GISTs. RESULTS: Of the 282 patients with low-risk GISTs who met inclusion criteria, 14 (4.96%) had recurrence or metastasis. There was a correlation between tumor size, primary site, resection type, Ki67 index, neutrophil lymphocyte ratio (NLR) and CD34 expression and postoperative recurrence or metastasis of GISTs (P < 0.05). Subsequently, multifactorial analysis showed that tumor primary site, tumor size, and Ki67 index were independent risk factors affecting postoperative recurrent or metastasis in patients with low-risk GISTs (P < 0.05). Ultimately, According to Kaplan-Meier analysis, non-gastric primary tumors, larger tumors, and high Ki67 index were significantly associated with poor progression-free survival ( PFS ). CONCLUSIONS: Tumor location, tumor size and Ki-67 were independent risk factors for postoperative recurrence and metastasis in patients with low-risk GISTs. Based on the 2008 modified NIH recurrence risk grading system, combined with the above three factors, it can be used to evaluate the prognosis of patients with low-risk GISTs and provide personalized postoperative review and follow-up management recommendations.

Transumbilical Endoscopic Resection of Intra-abdominal Mesenchymal Tumor.

Gastrointestinal stromal tumors (GISTs) typically occur in the stomach and proximal small intestine but can also be found in any other part of the digestive tract, including the abdominal cavity, albeit rarely. In the present case, the tumor was resected endoscopically through the anterior gastric wall. Computed tomography (CT) scan and gastroscopy of a 60-year-old woman revealed submucosal lesions in the gastric body. The possibility of a stromal tumor was considered more likely. The endoscopic surgery was performed under endotracheal anesthesia. After a solution had been injected at the lesion site in the stomach, the entire gastric wall was dissected to expose the tumor. As the lesion was in the abdominal cavity and its base was attached to the abdominal wall, it was accessed using a sterilized PCF colonoscope. A sodium chloride injection was administered at the base. The tumor was then peeled along its boundaries using the hooking and excision knife combined with the precutting knife. Subsequently, the tumor was pulled into the stomach through the incision made in the stomach and then extracted externally through the upper digestive tract using the ERCP spiral mesh basket. After confirming the absence of bleeding at the incision site, the endoscope was returned to the stomach, and the stomach opening was closed using purse-string sutures. The patient recovered satisfactorily following the surgery and was discharged on day 4. Histological examination revealed a low-risk stromal tumor (spindle cell type, <5 mitosis/50 high-power fields [HPF]). Immunohistochemistry revealed positive staining for CD34 and CD117, negative staining for SMA, positive staining for DOG1, and negative staining for S100. Additionally, the expression of ki67 was 3%.

Colonic gastrointestinal stromal tumor (GIST) presenting with colocolonic intussusception: A rare case report.

An 8-year-old spayed female British bulldog was presented with vomiting, hyporexia, and large-bowel diarrhea. Abdominal ultrasound revealed a focal colonic mass with an intussusception located immediately oral to the mass. The intussusception encompassed the ascending and transverse colon and was non-reducible. Colonic resection and anastomosis were completed to include the intussusception and colonic mass. Histopathological examination of the mass demonstrated a spindle cell neoplasm arising within the muscular wall of the intussuscepted segment that obliterated normal architecture. Mild-to-moderate cytoplasmic immunoreactivity of the tumor cell population for CD117 and smooth muscle actin was consistent with a diagnosis of a gastrointestinal stromal tumor. The dog described herein remains alive and free of progressive disease at the time of writing. Key clinical message: The entire gastrointestinal tract should be evaluated in any animal with gastrointestinal symptoms. A gastrointestinal stromal tumor remains a plausible differential diagnosis, regardless of the intestinal segment affected, and tumorassociated intussusception is a rare but urgent clinical finding.

Tumeur stromale gastro-intestinale du côlon (GIST) présentant une invagination colocolique : un rapport de cas rare. Une femelle bouledogue anglais stérilisée de 8 ans a présenté des vomissements, une hyporexie et une diarrhée d'origine du gros intestin. L'échographie abdominale a révélé une masse colique focale avec une invagination située immédiatement oralement à la masse. L'intussusception englobait le côlon ascendant et transverse et était non réductible. La résection colique et l'anastomose ont été réalisées pour inclure l'intussusception et la masse colique. L'examen histopathologique de la masse a révélé un néoplasme à cellules fusiformes apparaissant dans la paroi musculaire du segment invaginé qui a oblitéré l'architecture normale. L'immunoréactivité cytoplasmique légère à modérée de la population de cellules tumorales pour le CD117 et l'actine des muscles lisses étaient compatibles avec un diagnostic de tumeur stromale gastro-intestinale. Le chien décrit ici est toujours vivant et exempt de maladie évolutive au moment de la rédaction.Message clinique clé :L'ensemble du tractus gastro-intestinal doit être évalué chez tout animal présentant des symptômes gastrointestinaux. Une tumeur stromale gastro-intestinale reste un diagnostic différentiel plausible, quel que soit le segment intestinal atteint, et l'intussusception associée à la tumeur est une constatation clinique rare mais urgente.(Traduit par Dr Serge Messier).

[Reappraisals of biological behaviors of PDGFRA mutant gastrointestinal stromal tumor].

Objective: To investigate the biological behavior spectrum of platelet-derived growth factor alpha receptor (PDGFRA)-mutant gastrointestinal stromal tumor (GIST), and to compare the clinical values of the Zhongshan method of benign and malignant evaluation with the modified National Institutes of Health (NIH) risk stratification. Methods: A total of 119 cases of GIST with PDGFRA mutation who underwent surgical resection at Zhongshan Hospital, Fudan University from 2009 to 2020 were collected. The clinicopathological data, follow-up records, and subsequent treatment were reviewed and analyzed statistically. Results: There were 79 males and 40 females. The patients ranged in age from 25 to 80 years, with a median age of 60 years. Among them, 115 patients were followed up for 1-154 months, and 13 patients progressed to disease. The 5-year disease-free survival (DFS) and overall survival (OS) were 90.1% and 94.1%, respectively. According to the modified NIH risk stratification, 8 cases, 32 cases, 38 cases, and 35 cases were very-low risk, low risk, intermediate risk, and high risk, and 5-year DFS were 100.0%, 95.6%, 94.3%, and 80.5%, respectively. There was no significant difference in prognosis among the non-high risk groups, only the difference between high risk and non-high risk groups was significant (P=0.029). However, the 5-year OS was 100.0%, 100.0%, 95.0% and 89.0%, and there was no difference (P=0.221). According to the benign and malignant evaluation Zhongshan method, 43 cases were non-malignant (37.4%), 56 cases were low-grade malignant (48.7%), 9 cases were moderately malignant (7.8%), and 7 cases were highly malignant (6.1%). The 5-year DFS were 100.0%, 91.7%, 77.8%, 38.1%, and the difference was significant (P<0.001). The 5-year OS were 100.0%, 97.5%, 77.8%, 66.7%, the difference was significant (P<0.001). Conclusions: GIST with PDGFRA gene mutation shows a broad range of biological behavior, ranging from benign to highly malignant. According to the Zhongshan method, non-malignant and low-grade malignant tumors are common, the prognosis after surgery is good, while the fewer medium-high malignant tumors showed poor prognosis after surgical resection. The overall biological behavior of this type of GIST is relatively inert, which is due to the low proportion of medium-high malignant GIST. The modified NIH risk stratification may not be effective in risk stratification for PDGFRA mutant GIST.

Recent advances for treatment of upper gastrointestinal malignancy.

Recent prospective trials for esophageal cancer, gastric cancer, and gastrointestinal stromal tumor (GIST) are encouraging. This manuscript reviews selected recently published studies. Not surprisingly, immunotherapy dominates the current clinical trial landscape. However, targeted biologic therapies and standard chemotherapy remain critical to the treatment of gastric and esophageal cancer while imatinib remains the backbone for advanced or metastatic GISTs. For all three cancers, surgical resection remains important when intent of treatment is potential cure.

Gastric gastrointestinal stromal tumors: therapeutic strategies and long-term prognosis.

OBJECTIVES: This study aimed to evaluate the clinical and prognostic characteristics of primary gastric gastrointestinal stromal tumors (GIST). METHODS: Patients who underwent resection for primary gastric GIST between January 2002 and December 2017 were included. Recurrence-free survival (RFS) was calculated by Kaplan-Meier analysis, and Cox proportional hazards model was used to identify independent prognostic factors. RESULTS: Altogether, 653 patients were enrolled. The median patient age was 59 years (range 15-86 years). Open, laparoscopic, and endoscopic resections were performed in 394 (60.3%), 105 (16.1%), and 154 (23.6%) patients, respectively. According to the modified NIH consensus classification, 132 (20.2%), 245 (37.5%), 166 (25.4%), and 88 (13.5%) patients were categorized into very low-, low-, intermediate-, and high-risk, respectively. A total of 136 (20.8%) patients received adjuvant imatinib treatment. The median follow-up time was 78 months (range 4-219 months), and the estimated 5-year RFS rate was 93.0%. In all patients, tumor size and rupture, mitotic counts, and adjuvant imatinib treatment were independent prognostic factors. The prognosis of gastric GIST treated with endoscopic resection was not significantly different from that of laparoscopic or open resection after adjusting for covariates using propensity score matching (log-rank p = .558). Adjuvant imatinib treatment (HR = 0.151, 95%CI 0.055-0.417, p < .001) was a favorable prognostic factor for high-risk patients, but was not associated with prognosis in intermediate-risk patients. CONCLUSION: Patients with small gastric GISTs who successfully underwent endoscopic resection may have a favorable prognosis. Adjuvant imatinib treatment improve the prognosis of high-risk gastric GISTs, however, its use in intermediate-risk patients remains controversial.

Single-port intragastric wedge resection using the tunnel method: a novel surgical approach for treating endophytic gastric subepithelial tumors.

BACKGROUND: Intragastric wedge resection is an effective method for treating endophytic gastric subepithelial tumors (SETs). However, retracting the stomach wall to the umbilicus is difficult in certain patients. In response, we developed a novel surgical technique for single-port intragastric wedge resection, which we termed the "tunnel method." METHODS: A transumbilical incision is made, and a wound retractor is applied. After diagnostic laparoscopy, a gastrostomy is made on the greater curvature, lower body. Another small wound retractor is inserted into the gastrostomy, and extracted through the transumbilical incision, creating a tunnel from the gastrostomy site to the umbilicus. Articulating laparoscopic instruments are inserted via the tunnel, and intragastric wedge resection is performed. We collected and analyzed the clinicopathologic and operative data of patients who underwent intragastric wedge resection via the tunnel method. RESULTS: Twenty-seven patients who underwent single-port intragastric wedge resection via the tunnel method in a single tertiary referral hospital were included in this study. The mean age of the patients was 54.6 ± 11.4 years, body mass index was 26.5 ± 3.4 kg/m2. Twenty-four (88.9%) patients had tumors located in the upper third of the stomach. The average operative time was 65.0 ± 24.2 min. None of the patients experienced Clavien-Dindo grade IIIa or higher postoperative complications. The average postoperative hospital stay length was 2.5 ± 0.8 days. Thirteen gastrointestinal stromal tumors, nine leiomyomas, and one neuroendocrine carcinoma, schwannoma, lipoma, spindle cell proliferative lesion, and fibrotic lesion were pathologically diagnosed. The average tumor size was 2.6 ± 1.3 cm. All cases had negative resection margins. CONCLUSIONS: Single-port intragastric wedge resection by the tunnel method is a feasible and safe approach for treating endophytic gastric SETs.

Utility and costs of surveillance imaging for low- and very low-risk gastrointestinal stromal tumors.

BACKGROUND: There is limited evidence on the optimal surveillance approach in patients with low- and very low-risk gastrointestinal stromal tumors, resulting in inconsistent and arbitrary approaches to surveillance in this population. In this study, we reviewed our institutional approach to surveillance in patients with low- and very low-risk gastrointestinal stromal tumors and the costs associated with detecting recurrence. METHODS: We retrospectively reviewed consecutive adult patients treated for low- and very low-risk gastrointestinal stromal tumors at our institution from 2010 to 2019. Data collected included patient and tumor characteristics, surgical management, and postoperative follow-up. Surveillance-related expenses were calculated using estimates of average costs obtained from our institution. A cost analysis was performed to evaluate estimated yearly costs based on the surveillance strategy used. RESULTS: There were 60 patients included. The mean age at diagnosis was 63.9 (±12.5) years. The primary tumor was typically in the stomach (73%; n = 44). Computed tomography scan of the abdomen and pelvis with intravenous contrast was the most common surveillance modality (total = 226 scans). No recurrences were identified. Median follow-up duration was 49.0 (interquartile range = 19.5-61.5) months. The mean number of surveillance images per patient was 4 (±2.6). Surveillance imaging was obtained more frequently than just annually in 83% (n = 50) of patients, with an estimated yearly cost of $2,840.77 (interquartile range = $2,273.62-$3,895.92) and no detection of recurrence. CONCLUSION: In this study population, patients with low- and very low-risk gastrointestinal stromal tumors underwent frequent imaging studies for surveillance with little yield and at substantial cost. Further multi-institutional studies on practice patterns and outcomes of surveillance are warranted to better inform standardized surveillance recommendations.

Endoscopic resection for the treatment of gastric gastrointestinal stromal tumors: a retrospective study from a large tertiary hospital in China.

BACKGROUND AND AIMS: With the continuous development of endoscopic technology, endoscopic resection (ER) has gradually become an optional method for the treatment of gastric gastrointestinal stromal tumors (GISTs). However, studies with a large sample or a long follow-up are lacking. Therefore, this research aims to evaluate the efficacy and safety of ER for gastric GISTs in the real-world setting with more than 300 enrolled patients and a follow-up period longer than 45 months. METHODS: From January 2013 to February 2023, 409 patients with a pathological diagnosis of GISTs after ER were retrospectively enrolled in this study. After excluding 86 patients with non-gastric GISTs, we assessed 323 patients with gastric GISTs. The main outcome measures were en bloc resection, complete resection, residual disease, recurrence, and complications. RESULTS: There were 194 (60.06%) females and 129 (39.94%) males, and the median age of the included patients was 58 years (51, 63). The median tumor size was 15.0 (10.0, 20.0) mm. According to the modified NIH criteria, 246 (75.85%) patients were classified as very low risk, 62 (19.20%) were classified as low risk, 12 (3.72%) were classified as moderate risk, and 3 (0.93%) were classified as high risk. A total of 287 (88.85%) patients achieved en bloc resection, and 287 (88.85%) also achieved complete resection. Only one patient showed residual and no recurrent lesions were noted during the follow-up. Regarding complications, three patients had complications, with a complication rate of 0.93%, and no severe complications requiring surgical intervention occurred. CONCLUSION: ER is an appropriate alternative method for the treatment of gastric GISTs, with an en bloc resection rate of 88.85% and a complication rate of 0.93%. No recurrence was noted during follow-up, even for GISTs with piecemeal resection.

Percutaneous ultrasound-guided radiofrequency ablation for patients with liver metastases from gastrointestinal stromal tumors.

OBJECTIVES: This study aimed to analyze the survival outcomes and prognostic factors of radiofrequency ablation (RFA) for liver metastases from gastrointestinal stromal tumors (GISTs). METHODS: Between March 2011 and November 2022, 34 patients (16 males; age range, 25-72 [median age, 52.5] years) who underwent RFA for liver metastasis from GISTs were included. The mean maximum diameter of metastatic lesions was 2.4 ± 1.0 (range, 1.1-5.2) cm. Survival curves were constructed using the Kaplan-Meier method and compared using the log-rank test. Multivariate analyses were performed using a Cox proportional hazards model. RESULTS: For 79 lesions among 34 patients, all targeted lesions were completely ablated. The mean hepatic progression-free survival (HPFS) period was 28.4 ± 3.8 (range, 1.0-45.7) months. The 1-, 3-, and 5-year HPFS rates were 67.2%, 60.5%, and 20.2%, respectively. Based on the univariate analysis, the number of metastatic tumors and tyrosine kinase inhibitors(TKI) therapy before RFA were prognostic factors for HPFS. Multivariate analysis showed that pre-RFA TKI therapy was associated with a better HPFS(p = 0.030). The mean overall survival (OS) period was 100.5 ± 14.1 (range, 3.8-159.5) months and the 1-, 3-, and 5-year survival rates were 96.9%, 77.1%, and 58.7%, respectively. Both univariate and multivariate analysis indicated that extrahepatic metastasis before RFA (p = 0.044) was a significant prognostic factor for OS. CONCLUSIONS: Liver metastases from GIST exhibit relatively mild biological behavior. RFA is safe and effective, particularly in patients without pre-RFA extrahepatic metastases. Patients received targeted therapy before RFA can obtain an extended HPFS.