Liver-limited Metastases Research Articles

Comparison of systemic treatments for previously treated patients with unresectable colorectal liver metastases: a systematic review and network meta-analysis.

There is limited evidence of comparative results among different treatments for patients with unresectable colorectal liver metastases (CRLM) who have failed at least one line of previous systemic therapy. We aimed to compare the efficacy of systemic treatments among these patients through this investigation. We collected randomized controlled trials (RCTs) reported in English up until July 2023, from databases including PubMed, Embase, Cochrane Library, ClinicalTrials.gov, and prominent conference databases, for this Bayesian network meta-analysis. Phase II or III trials that evaluated at least two therapeutic regimens were included. Primary outcome was overall survival (OS), secondary outcome was progression-free survival (PFS). Hazards ratios (HRs) with 95% confidence intervals (CIs) were used as effect size. Subgroup analysis was performed based on metastatic sites. The current systematic review protocol was registered on PROSPERO (CRD42023420498). 30 RCTs were included, with a total of 13,511 patients. Compared to chemotherapy, multi-targeted therapy (HR 0.57, 95% CI 0.37-0.87) and targeted therapy plus chemotherapy (HR 0.78, 95% CI 0.67-0.91) show significant advantages. Targeted therapy (HR 0.92, 95% CI 0.54-1.57) and local treatment plus chemotherapy (HR 1.03, 95% CI 0.85-1.23) had comparable performance. For patients with liver metastases, TAS-102 plus bevacizumab, aflibercept plus fluorouracil-based combination chemotherapy (CTFU), and bevacizumab plus capecitabine-based combination chemotherapy (CTCA) showed the best outcomes in terms of OS. Bevacizumab plus intensified CTFU, bevacizumab plus CTCA, and HAI followed by single-agent chemotherapy (SingleCT) performed the best regarding PFS. For patients with liver-limited metastases, aflibercept plus CTFU is the optimal choice in OS. For PFS, the best options were HAI followed by SingleCT, aflibercept plus CTFU, and panitumumab plus CTFU. For patients with multiple-site metastases, the best treatments were TAS-102 plus bevacizumab, bevacizumab plus CTCA, bevacizumab plus CTFU, and aflibercept plus CTFU. Multi-targeted therapy and targeted therapy plus chemotherapy are the best treatment mechanisms. TAS-102 plus bevacizumab is superior in OS, the combination of anti-VEGF drugs like bevacizumab and aflibercept with standard chemotherapy is the preferred option for CRLM patients.

A proliferative subtype of colorectal liver metastases exhibits hypersensitivity to cytotoxic chemotherapy

Personalized treatment approaches for patients with limited liver metastases from colorectal cancer are critically needed. By leveraging three large, independent cohorts of patients with colorectal liver metastases (n = 336), we found that a proliferative subtype associated with elevated CIN70 scores is linked to immune exclusion, increased metastatic proclivity, and inferior overall survival in colorectal liver metastases; however, high CIN70 scores generate a therapeutic vulnerability to DNA-damaging therapies leading to improved treatment responses. We propose CIN70 as a candidate biomarker to personalize systemic treatment options for patients with metastatic colorectal cancer. These findings are potentially broadly applicable to other human cancers.

Abstract 519: Clinical impact ofKRASG12, G13, Q61, K117 and A146 mutations in patients with colorectal liver metastases

Abstract Introduction: The distribution of KRAS mutation variants across tumor types is not uniform. The KRAS A146 mutation is predominantly seen in colorectal cancer (CRC) patients. Here, we evaluated how clinical features like tumor load and overall survival differ between metastatic CRC (mCRC) patients carrying distinct somatic KRAS G12, G13, Q61, K117 or A146 mutations. Methods: 419 CRC patients with initially unresectable liver-limited metastases, who participated in the multicenter CAIRO5 prospective clinical trial, were evaluated for tumor tissue KRAS mutation status. For the subgroup of patients who carried a KRAS mutation and were treated with bevacizumab and doublet or triplet chemotherapy (N=156), clinical outcome was evaluated and pretreatment tumor burden was quantified as liquid biopsy circulating tumor DNA (ctDNA) mutant allele fraction (MAF) and as total tumor volume (TTV) on CT imaging. The MAF, TTV and overall survival were compared between patients harboring different KRAS mutation variants. Results: Of the 156 patients with a KRAS mutated tumor, most carried a KRAS G12 mutation (N=112, 71.8%), followed by mutations in G13 (N=15, 9.6%), A146 (N=12, 7.7%), Q61 (N=9, 5.8%) and K117 (N=5, 3.2%). High plasma ctDNA levels were observed for patients carrying a KRAS A146 mutation versus those with a KRAS G12 mutation, with a median MAF of 48% versus 19%, respectively. Radiological TTV revealed this difference to be associated with a higher tumor load in patients harboring a KRAS A146 mutation (median TTV 672 cm3 (A146) versus 74 cm3 (G12), p=0.036). Moreover, KRAS A146 mutation carriers showed inferior overall survival compared to patients with mutations in KRAS G12 (median 10.7 versus 26.4 months; HR=2.5; p=0.003), and the multivariable Cox regression analysis showed that the KRAS alteration was the only independent prognostic factor for overall survival. Conclusion and Relevance: This study revealed that within mCRC patients A146 is the third most common KRAS mutation variant, and mCRC patients carrying a KRAS A146 mutation represent a distinct molecular subtype of patients with high tumor burden and poor clinical outcome. This highlights the importance of testing CRC for all KRAS mutations in routine clinical care and shows the opportunity for personalized treatment beyond detecting the presence of a KRAS mutation by taking the specific KRAS mutation variant into account. Citation Format: Iris van 't Erve, Nina J. Wesdorp, Jamie E. Medina, Leonardo Ferreira, Alessandro Leal, Joost Huiskens, Karen Bolhuis, Jan-Hein T. van Waesberghe, Rutger-Jan Swijnenburg, Daan van den Broek, Victor E. Velculescu, Geert Kazemier, Cornelis J. Punt, Gerrit A. Meijer, Remond J. Fijneman. Clinical impact ofKRASG12, G13, Q61, K117 and A146 mutations in patients with colorectal liver metastases [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 519.

The optimal treatment sequence for patients with stage IV rectal cancer and limited liver metastases: a nationwide comparison of two strategies.

Background: In the Netherlands, different treatments sequences are used for rectal cancer patients with resectable synchronous liver metastases. Two common sequences used are the M1-scheme (M1) and the liver-first approach (LF). The aim of this study was to compare the oncological outcomes of patients treated with M1 and LF.

MFOLFOXIRI+Bev vs. mFOLFOX6+Bev for RAS mutant unresectable colorectal liver-limited metastases: A study protocol of a multicenter randomized controlled phase 3 (BECOME2) trial.

TPS228 Background: Colorectal cancer patients with initially unresectable liver-only metastases may be cured after downsizing of metastases by conversion therapy. However, the optimal regimen of conversion therapy for RAS mutant patients has not been defined. Methods: BECOME2 is a multicenter, randomized, phase 3 clinical study. RAS mutant and BRAF wild type colorectal cancer patients with initially unresectable liver-limited metastases are eligible. The (un)resectability status is prospectively assessed by a central multidisciplinary team (MDT) consisting of at least one radiologist and three liver surgeons, according to predefined criteria. RAS and BRAF mutation status were evaluated according to primary tumor. Patients with RAS mutant and BRAF wild type will be randomized between modified FOLFOXIRI (IRI, 165mg/m2; Oxa, 85mg/m2; LV, 400mg/m2; 5-FU 2400mg/m2) plus bevacizumab (5mg/kg) and modified FOLFOX6 (mFOLFOX6) plus bevacizumab. Radiological evaluation to assess conversion to resectability will be performed by the central MDT every eight weeks. The primary study endpoint is conversion resection rate. Secondary endpoints are the ETS, DpR, ORR, PFS, OS, toxicity, perioperative complication, and the proportion of no evidence of disease. Clinical trial information: NCT04781270.

ASO Visual Abstract: Outcomes of Combined Peritoneal and Local Treatment in Patients with Peritoneal and Limited Liver Metastases of Colorectal Origin: A Systematic Review and Metaanalysis

ASO Visual Abstract: Outcomes of Combined Peritoneal and Local Treatment in Patients with Peritoneal and Limited Liver Metastases of Colorectal Origin: A Systematic Review and Metaanalysis

A Nomogram to Predict Individual Survival of Patients with Liver-Limited Metastases from Gastroenteropancreatic Neuroendocrine Neoplasms: A US Population-Based Cohort Analysis and Chinese Multicenter Cohort Validation Study

Introduction: Although gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) with liver metastasis encompass a wide variety of clinical conditions with various prognosis, no statistical model for predicting the prognosis of these patients has been established. We sought to establish a more elaborative and individualized nomogram to predict survival of patients with liver-limited metastatic GEP-NENs. In addition, this nomogram was validated by both the Surveillance, Epidemiology, and End Results (SEER) database and a Chinese multicenter cohort. Methods: Patients diagnosed with GEP-NENs with liver-limited metastasis between 2010 and 2016 were identified from the SEER database. Kaplan-Meier survival analysis was performed to analyze survival outcomes. A nomogram was established based on the independent prognostic variables identified from univariate and multivariate Cox regression analyses. The nomogram was evaluated in both an internal validation SEER dataset and an external validation dataset composed of patients from the Chinese multicenter cohort. Results: A total of 1,474 patients from the SEER database and 192 patients from the multicenter cohort were included. Age, tumor size, differentiation, primary tumor resection, and liver metastasis resection were identified as independent prognostic factors by univariate and multivariate Cox analyses and were verified by Kaplan-Meier survival analysis (all p < 0.0001). A nomogram was developed and validated by calibration curves and areas under the curve of the external validation cohort, which showed good consistency and veracity in predicting overall survival. Conclusion: A nomogram was developed for the first time to predict the survival of patients with liver-limited metastases from GEP-NENs. Both internal and external validation demonstrated excellent discrimination and calibration of our nomogram. Based on this prognostic model, clinicians could develop more personalized treatment strategies and surveillance protocols.

Laparoscopic vs. Open Resection for Colorectal Liver Metastases

Hepatic resection for limited liver metastases from colorectal cancer leads to long-term survival in select patients, and retrospective studies have

Liver resection for colorectal liver-limited metastases in elderly patients: a propensity score matching analysis

BackgroundFew studies have focused on the role of hepatectomy for colorectal liver-limited metastases in elderly patients compared to matched younger patients.MethodsFrom January 2000 to December 2018, 724 patients underwent hepatectomy for colorectal liver-limited metastases. Based on a 1:2 propensity score matching (PSM) model, 64 elderly patients (≥ 70 years of age) were matched to 128 younger patients (< 70 years of age) to obtain two balanced groups with regard to demographic, therapeutic, and prognostic factors.ResultsThere were 73 elderly and 651 younger patients in the unmatched cohort. Compared with the younger group (YG), the elderly group (EG) had significantly higher proportion of American Society of Anesthesiologists score III and comorbidities and lower proportion of more than 3 liver metastases and postoperative chemotherapy (p < 0.05). After PSM for these factors, rat sarcoma virus proto-oncogene/B-Raf proto-oncogene (RAS/BRAF) mutation status and primary tumor sidedness, the EG had significantly less median intraoperative blood loss than the YG (175 ml vs. 200 ml, p = 0.046), a shorter median postoperative hospital stay (8 days vs. 11 days, p = 0.020), and a higher readmission rate (4.7% vs.0%, p = 0.036). The EG also had longer disease-free survival (DFS), overall survival (OS), and cancer-specific survival (CSS) compared to the YG, but these findings were not statistically significant (p > 0.05). Old age was not an independent factor for DFS, OS, and CSS by Cox multivariate regression analysis (p > 0.05).ConclusionsHepatectomy is safe for colorectal liver-limited metastases in elderly patients, and these patients may subsequently benefit from prolonged DFS, OS, and CSS.

Patterns of hepato-pulmonary metastasis and their impact on clinical outcomes in uveal melanoma.

e22052 Background: Metastatic Uveal Melanoma (MUM) is a rare tumor with poor prognosis following development of liver metastasis. We hypothesized that patterns of metastasis in Uveal Melanoma correlate with clinical outcomes. Methods: We retrospectively reviewed patients with MUM at Mayo Clinic, Rochester from January 1999 to August 2019. Patients were stratified into two groups based on the pattern of hepatic and pulmonary metastasis at the time of diagnosis of metastatic disease: Group 1 (≤5 liver metastasis or lung metastasis) and Group 2 ( &gt; 5 liver metastasis without lung metastasis). Baseline characteristics were compared between both groups. Survival analysis was performed using the Kaplan Meier method. Univariate and multivariate analysis were performed for Overall Survival (OS). Results: 147 patients were included in the study (n = 67 Group 1; n = 80 Group 2). In Group 1, 49/67 patients presented with ≤5 liver metastasis and 18/67 had lung metastasis without liver metastasis. Median OS for Group 1 was significantly longer than Group 2 (38 vs. 15 months; p &lt; 0.0001) (Table). On univariate analysis, predictors for OS were: Pattern of Metastasis, ECOG PS &gt; 0, Time to metastasis &gt; 60 months, and Surgical metastatectomy. Pattern of Metastasis was an independent predictor for OS in a multivariate model that included these predictors (p = 0.0004). Group 1 patients were more likely to undergo surgical metastatectomy compared to group 2 (21.5% vs. 1.3%; p &lt; 0.0001). Interestingly, the median time to metastasis from diagnosis of UM was significantly longer for Group 1 as compared to Group 2 (67 vs. 24.5 months; p &lt; 0.0001). Conclusions: Limited (≤5) liver metastasis or lung metastasis (without liver metastasis) at diagnosis predict favorable clinical outcomes in MUM. The occurrence of such metastasis following a significantly longer time from primary diagnosis suggests the existence of a distinct sub-type of metastatic disease with relatively indolent behavior. [Table: see text]

Effect of Chinese Herbal Medicine on the Survival of Colorectal Cancer Patients With Liver-Limited Metastases: A Retrospective Cohort Study, 2008 to 2017.

Background: Colorectal cancer (CRC) remains one of the leading contributors to cancer-related mortality and morbidity worldwide. Traditional Chinese medicines have been widely employed to treat various types of cancer in China. This investigation aims to determine the association between Chinese herbal medicine (CHM) therapy and survival outcomes in CRC patients with liver-limited metastases. Methods: A retrospective cohort study was performed among patients with colorectal liver metastases at the First Affiliated Hospital of Guangzhou University of Chinese Medicine in Guangzhou, China. Data from a series of consecutive patients were collected via an electronic medical record system or telephone follow-up. We defined high exposure as a period of CHM therapy lasting more than 6 months. The primary outcome was overall survival. Results: The study included the data of 191 patients from January 2008 to December 2017; 126 patients (65.97%) met the inclusion criteria of high exposure to CHM. Multivariate analyses revealed that high exposure to CHM was associated with better overall survival (hazard ratio = 0.444, 95% confidence interval = [0.213, 0.926], P = .030). The association was further confirmed by a subgroup exploratory analysis. Conclusion: Long-term CHM therapy is correlated with improved survival outcomes in CRC patients with liver-limited metastases.

The role of interventional oncology in the treatment of colorectal cancer liver metastases.

Colorectal cancer is a leading cause of death both in Europe and worldwide. Unfortunately, 20-25% of patients with colorectal cancer already have metastases at the time of diagnosis, while 50-60% of the remainder will develop metastases later during the course of the disease. Although hepatic excision is the first-line treatment for patients with liver-limited colorectal metastases and is reported to prolong the survival of these patients, few patients are candidates. Locoregional therapy encompasses minimally invasive techniques practiced by interventional radiology. Most widely used locoregional therapies include ablative treatments (radiofrequency ablation, microwave ablation) and transcatheter intra-arterial therapies (transarterial chemoembolization, and radioembolization with yttrium-90).

518P - Hepatic arterial infusion (HAI) of oxaliplatin with capecitabine in first line treatment of patients (pts) with liver limited metastases from colorectal cancer (LLmCRC)

518P - Hepatic arterial infusion (HAI) of oxaliplatin with capecitabine in first line treatment of patients (pts) with liver limited metastases from colorectal cancer (LLmCRC)

THE EFFICIENCY OF STEREOTAXIC RADIOTHERAPY IN PATIENTS WITH LIVER METASTASES

Aim. To determine the effectiveness of stereotaxic radiotherapy in patients with liver metastases. Material and Methods. Stereotaxic radiotherapy of liver metastatic tumors was carried out in three fractions for 5–8 days with single focal dose of 10, 12, 15, or 20 Gy. The procedure was performed in 66 patients including 40 (60.5%) women and 26 (39.5%) men. The average age was 60 years (37–82). In 24 (36.5%) cases primary tumor was presented by colorectal cancer, in 12 (18%) – breast cancer, in 7 (10.5%) – ovarian cancer and in 23 (35%) – other malignant tumors. Results. Median follow-up was 14.5 months (range 1.8–53.5). 3 patients did not present data of control examination. Among other 63 patients full effect was established in 16 (25.5%) cases, in 30 (47.5%) patients – partial regression of metastases, in 11 (17.5%) – stabilization, in 6 (9.5%) – progression of tumoral process. Thus, local control rate was 90.5%. Degree III of radiation damage was reported in 2 cases (3%), II – in 7 cases (11%). Conclusion. Stereotaxic radiotherapy seems highly effective and safe method of the treatment of patients with liver metastases and can be recommended for use in patients with limited liver metastases who have been denied in surgery.

A phase I trial of Proton stereotactic body radiation therapy for liver metastases.

A phase I trial to determine the maximum tolerated dose (MTD) of Proton stereotactic body radiation therapy (SBRT) for liver metastases in anticipation of a subsequent phase II study. An institutional IRB approved phase I clinical trial was conducted. Eligible patients had 1-3 liver metastases measuring less than 5 cm, and no metastases location within 2 cm of the GI tract. Dose escalation was conducted with three dose cohorts. The low, intermediate, and high dose cohorts were planned to receive 36, 48, and 60 respectively to the internal target volume (ITV) in 3 fractions. At least 700 mL of normal liver had to receive <15. Dose-limiting toxicity (DLT) included acute grade 3 liver, intestinal or spinal cord toxicity or any grade 4 toxicity. The MTD is defined as the dose level below that which results in DLT in 2 or more of the 6 patients in the highest dose level cohort. Nine patients were enrolled (6 male, 3 female): median age 64 years (range, 33-77 years); median gross tumor volume (GTV) 11.1 mL (range, 2.14-89.3 mL); most common primary site, colorectal (5 patients). Four patients had multiple tumors. No patient experienced a DLT and dose was escalated to 60 in 3 fractions without reaching MTD. The only toxicity within 90 days of completion of treatment was one patient with a grade 1 skin hyperpigmentation without tenderness or desquamation. Two patients in the low dose cohort had local recurrence and repeat SBRT was done to previously treated lesions without any toxicities. Biologically ablative Proton SBRT doses are well tolerated in patients with limited liver metastases with no patients experiencing any grade 2+ acute toxicity. Results from this trial provide the grounds for an ongoing phase II Proton SBRT study of 60 over 3 fractions for liver metastases.

A randomized phase II study of mFOLFOX6 plus bevacizumab versus mFOLFOX6 plus cetuximab for previously untreated, liver-limited metastatic colorectal cancer that is unsuitable for resection (ATOM trial).

734 Background: It is still a topic of ongoing debate as to which of the two agents, anti-VEGF antibody or anti-EGFR antibody, is more effective in patients with KRAS Exon 2 or RAS wild-type metastatic colorectal cancer (mCRC) in the first-line setting. ATOM is a multicenter, randomized trial comparing mFOLFOX6 plus bevacizumab (Bmab arm) with mFOLFOX6 plus cetuximab (Cmab arm) in patients with liver-limited metastases unsuitable for upfront resection. Methods: Patients with previously untreated mCRC were eligible if they had ≥5 liver-limited metastatic lesions and/or had liver-limited metastases with the maximum lesion diameter of &gt; 5cm. Patients with KRAS Exon2-wild were registered but after Jan 2015 limited to those with all RAS-wild. Primary endpoint was progression-free survival (PFS), which was defined as the time from randomization to disease progression, recurrence after resection by surgery, or death from any cause (Central review). Key secondary endpoints included overall response rate (ORR), liver resection rate, and overall survival (OS). Results: A total of 122 pts were enrolled between May 2013 and April 2016. Of 116 eligible (59 in the Cmab arm and 57 in the Bmab arm), median age was 65/64 in the Cmab/Bmab arm; ECOG PS 0, 86/89%; all RAS wt, 98/95%; left-sided primary tumor, 76/84%. Efficacy results were summarized in the table. With a median follow-up of 24.3 months, the median PFS was 15.0 months in Cmab arm and 11.6 months in the Bmab arm with a hazard ratio of 0.803 (95%CI, 0.513–1.256), whereas ORR was 86% in the Cmab arm and 68% in the Bmab arm. Liver resection rate was 49% and 56% in the Cmab arm and the Bmab arm, respectively. Conclusions: In patients considered unsuitable for upfront resection of liver-limited metastasis, the two agents showed a similar efficacy. OS result will be presented elsewhere. Clinical trial information: NCT01836653. [Table: see text]

Abstract A052: Predictive wild-type RAS/BRAF and pharmacogenetic biomarkers drive selection of metastatic colorectal cancer patients fit for intensive first-line FIr-C/FOx-C schedule adding cetuximab to triplet chemotherapy

Abstract Background: Intensive-first line bevacizumab (BEV) addition to triplet chemotherapy significantly increased clinical outcome in metastatic colorectal cancer (MCRC) patients. Cetuximab (CET) addition to doublet chemotherapy significantly increased clinical outcome in RAS wild-type MCRC. This phase II study investigated safety and activity of FIr-C/FOx-C schedule of weekly CET added to triplet chemotherapy in first line RAS wild-type MCRC. Methods: The phase II study was planned according to Simon two-step design: delta 15% (p0 70%, p1 85%), power 80%, α 5%, β 20%; projected objective responses (ORR), I step 14/19 patients. FIr-C/FOx-C schedule: 5-fluorouracil (5-FU) 12h-timed-flat-infusion 900 mg/m2, days 1-2, 8-9, 15-16, 22-23; associated to weekly alternating irinotecan (CPT-11) 160 mg/m2, days 1,15 or oxaliplatin (OXP) 80 mg/m2, days 8, 22; CET 400 mg/m2 loading dose, then 250 mg/m2 days 1,8,15,22; every 4 weeks. Toxicity and limiting toxicity syndromes (LTS) were evaluated and compared using chi-square test; activity and efficacy using log-rank test. 5-FU degradation rate (5-FUDR) and single nucleotide polymorphisms (SNP) of 4 genes (DYPD, CYP3A4, ABCB1, UGT1A1) involved in metabolism of 5-FU and CPT-11 were evaluated in individual patients showing LTS and at the recommended doses as predictive biomarkers of toxicity. Results: Twenty-nine consecutive patients &amp;lt;75 years with primary/intermediate Cumulative Illness Rating Scale (CIRS) were enrolled. From April 2014, only KRAS/NRAS wild-type patients were eligible: median age 59; young-elderly (yE) 7 (24%); liver-limited metastases (L-L) 7, 24%. Due to limiting gastrointestinal toxicity, recommended doses of CPT-11 and 5-FU were 120 and 750 mg/m2, respectively. Activity data met the primary endpoint: 14 OR out of 18 evaluable patients as treated (76%). Preliminary phase II data confirm 17 OR out of 23 evaluable patients intent-to-treat (74%). Liver metastasectomies were performed in 14%, 57% L-L. At median follow-up 18 months, median progression-free survival (PFS) was 12 months, median overall survival (OS) 23 months. OS was significantly worse in yE compared to non-elderly patients (p = 0.045). At the recommended doses, received DI was &amp;gt;80% for each drug and cumulative G3-4 toxicities in 13 patients were: diarrhea 23%, asthenia 15%, vomiting 8%, hypertransaminasemy 8%. LTS, consisting of the LT, associated or not to G2 or other LT, were observed overall in 19 patients (65.5%), 83% in yE. LTS were prevalently multiple than single site (59% versus 7%, chi square 7.703, p = 0.006). Reduced FUDR, CYP3A4 and UGT1A1 SNPs, also frequently associated, were particularly observed in patients showing gastrointestinal LTS, while not in patients without LTS. Conclusion: Intensive first-line FIr-C/FOx-C regimen at the modified recommended doses is tolerable and highly effective in RAS wild-type MCRC patients, with significantly increased LTS multiple sites, justifying careful selection of fit patients using a panel of 5 predictive biomarkers of 5-FU and CPT11 toxicity. Citation Format: Gemma Bruera, Silvia Massacese, Antonella Dal Mas, Corrado Ficorella, Eugenio Ciacco, Giuseppe Calvisi, Maurizio Simmaco, Enrico Ricevuto. Predictive wild-type RAS/BRAF and pharmacogenetic biomarkers drive selection of metastatic colorectal cancer patients fit for intensive first-line FIr-C/FOx-C schedule adding cetuximab to triplet chemotherapy [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr A052.

Role of hepatectomy in gastric cancer with multiple liver-limited metastases.

Several studies have demonstrated the benefit of hepatectomy for treating gastric cancer (GC) with liver-limited metastases (LLM). The survival benefit of hepatectomy compared with that of systemic chemotherapy is unknown, particularly in patients with multiple LLM. This study investigated the survival benefit of hepatectomy compared with that of systemic chemotherapy administered to patients with GC with multiple LLM. We retrospectively reviewed the data of consecutive patients with GC with two or three LLM who underwent hepatectomy or received systemic chemotherapy as initial treatment at the Shizuoka Cancer Center between December 2004 and December 2015. Nine of 24 patients who met the inclusion criteria underwent hepatectomy, and 15 received chemotherapy. In the hepatectomy group, all patients achieved R0 resection and none died during hospitalization. Three patients received adjuvant chemotherapy. Disease recurred in eight patients (88.9%). In the chemotherapy group, three patients underwent hepatectomy following initial chemotherapy and did not experience recurrence or death during follow-up. Median follow-up was 47.9months and median overall survival (OS) was 38.1 and 24.8months in the chemotherapy and hepatectomy groups, respectively. Multivariate analysis of OS, including initial treatment, revealed that unilobar liver metastasis was the only independent favorable prognostic factor. Although hepatectomy for patients with GC with multiple LLM is not recommended as the initial therapy, it prolonged the survival of patients with tumors controlled using systemic chemotherapy.

A Comparison of Survival by Site of Metastatic Resection in Metastatic Colorectal Cancer

BackgroundMetastatic resection (MR) of liver-limited disease is an effective therapy for selected patients with metastatic colorectal cancer (mCRC). Despite limited data, this approach has been expanded to include MR of other sites, such as the lung, locoregional, and other distant disease (ODD). We performed a population-based study of patients with mCRC who had undergone MR and compared survival between MR of the liver and MR of other sites. MethodsPatients with mCRC who were referred to the British Columbia Cancer Agency between 1995 and 2010 were reviewed. Patients were included if they had an R0 MR with a negative margin and no residual disease. The site of MR was classified according to collaborative staging criteria as liver, lung, locoregional, or ODD. Median overall survival (mOS) was assessed with Kaplan–Meier methods and compared using the log-rank test. A Cox proportional-hazards model was used to compare mOS, while adjusting for known prognostic factors. ResultsA total of 2082 patients with mCRC were identified, of whom 257 underwent R0 MR. Sites of MR included liver (65%), lung (16%), locoregional (5%), and ODD (14%). The mOS of liver, lung, locoregional, and ODD were 48.0, 42.8, 37.2, and 26.2 months, respectively (P = .087). On multivariate analysis, only MR of ODD had a significantly different survival estimate than MR of the liver (hazard ratio, 1.78; 95% confidence interval, 1.13-2.80; P = .012). ConclusionsPatients with limited lung and locoregional disease seem to have a comparable survival advantage from MR as patients with liver-limited metastases.

Searching for predictive biomarkers on the efficacy of cetuximab plus chemotherapy for patients with unresectable colorectal liver-limited metastases: An expended biomarker analysis based on BELIEF study.

e15079Background: To identify predictive biomarkers for the efficacy of cetuximab. Materials and Methods: The DNA samples from 106 patients were sequenced for single nucleotide polymorphisms (SNPs)...