Development and implementation of an institutional enhanced recovery program data process.

Background: With increasing implementation of enhanced recovery programs (ERPs) in clinical practice, standardised data collection and reporting have become critical in addressing the heterogeneity of metrics used for reporting outcomes. Opportunities exist to leverage electronic health record (EHR) systems to collect, analyse, and disseminate ERP data. Objectives: (i) To consolidate relevant ERP variables into a singular data universe; (ii) To create an accessible and intuitive query tool for rapid data retrieval. Method: We reviewed nine established individual team databases to identify common variables to create one standard ERP data dictionary. To address data automation, we used a third-party business intelligence tool to map identified variables within the EHR system, consolidating variables into a single ERP universe. To determine efficacy, we compared times for four experienced research coordinators to use manual, five-universe, and ERP Universe processes to retrieve ERP data for 10 randomly selected surgery patients. Results: The total times to process data variables for all 10 patients for the manual, five universe, and ERP Universe processes were 510, 111, and 76 min, respectively. Shifting from the five-universe or manual process to the ERP Universe resulted in decreases in time of 32% and 85%, respectively. Conclusion: The ERP Universe improves time spent collecting, analysing, and reporting ERP elements without increasing operational costs or interrupting workflow. Implications: Manual data abstraction places significant burden on resources. The creation of a singular instrument dedicated to ERP data abstraction greatly increases the efficiency in which clinicians and supporting staff can query adherence to an ERP protocol.

Survival by Number and Sites of Resections of Recurrence after First Curative Resection of Colorectal Liver Metastases.

BACKGROUND: Recurrence after curative hepatectomy for colorectal liver metastases (CRLM) is common. We sought to determine if number and sites of resections of recurrence after hepatectomy for CRLM impact survival. METHODS: The study included patients who underwent resection of recurrence following complete curative-intent resection of CRLM during 1998-2016 at two academic medical centers in Houston, USA, and Rome, Italy. The survival impacts of number and sites of resections of recurrence were evaluated. Patients with synchronous extrahepatic disease at curative CRLM resection were excluded. RESULTS: Among 2163 patients who underwent curative hepatectomy, 1456 (67.3%) developed a recurrence. Four hundred seventy-eight patients underwent one (322/478; 67.4%) or two or more (156/478; 32.6%) resections of recurrence. The 5-year overall survival (OS) rate was higher in patients with resected than unresected recurrence (70.2% vs. 24.0%; p < 0.001). In patients who underwent only one resection of recurrence, the 5-year OS rate differed by location (lung, 81.6%; liver, 64.3%; other, 54.1%). In patients who underwent two or more resections of recurrence, the 5-year OS rate was similar for liver-only resection (87.5%) and resection of liver and other sites (66.1%) (p = 0.223) and for liver-only resection and other-sites-only resection (80.7%) (p = 0.258); 5-year OS rate by site of first resection of recurrence did not differ between liver (78.5%) and lung (81.8%) (p = 0.502) but was worse for other sites (61.1%) than for lung (p = 0.045). CONCLUSION: When recurrence after initial CRLM resection is resectable, the ability to undergo resection was associated with improved survival and can be considered as an option regardless of the number of recurrence and resection. Sites of resection of recurrence impact survival and should be considered.

Comparison of Severe Maternal Morbidities Associated With Delivery During Periods of Circulation of Specific SARS-CoV-2 Variants.

Importance: Infection with SARS-CoV-2, which causes COVID-19, is associated with adverse maternal outcomes. While it is known that severity of COVID-19 varies by viral strain, the extent to which this variation is reflected in adverse maternal outcomes, including nonpulmonary maternal outcomes, is not well characterized. Objective: To evaluate the associations of SARS-CoV-2 infection with severe maternal morbidities (SMM) in pregnant patients delivering during 4 pandemic periods characterized by predominant viral strains. Design, Setting, and Participants: This retrospective cohort study included patients delivering in a multicenter, geographically diverse US health system between March 2020 and January 2022. Individuals with SARS-CoV-2 infection were propensity-matched with as many as 4 individuals without evidence of infection based on demographic and clinical variables during 4 time periods based on the dominant strain of SARS-CoV-2: March to December 2020 (wild type); January to June 2021 (Alpha [B.1.1.7]); July to November 2021 (Delta [B.1.617.2]); and December 2021 to January 2022 (Omicron [B.1.1.529]). Data were analyzed from October 2021 to June 2022. Exposures: Positive SARS-CoV-2 nucleic acid amplification test result during the delivery encounter. Main Outcomes and Measures: The primary outcome was any SMM event, as defined by the US Centers for Disease Control and Prevention, during hospitalization for delivery. Secondary outcomes were number of SMM, respiratory SMM, nonrespiratory SMM, and nontransfusion SMM events. Results: Over all time periods, there were 3129 patients with SARS-CoV-2, with a median (IQR) age of 29.1 (24.6-33.2) years. They were propensity matched with a total of 12 504 patients without SARS-CoV-2, with a median (IQR) age of 29.2 (24.7-33.2) years. Patients with SARS-CoV-2 infection had significantly higher rates of SMM events than those without in all time periods, except during Omicron. While the risk of any SMM associated with SARS-CoV-2 infection was increased for the wild-type strain (odds ratio [OR], 2.74 [95% CI, 1.85-4.03]) and Alpha variant (OR, 2.57 [95% CI, 1.69-4.01]), the risk during the Delta period was higher (OR, 7.69 [95% CI, 5.19-11.54]; P for trend < .001). The findings were similar for respiratory complications, nonrespiratory complications, and nontransfusion outcomes. For example, the risk of nonrespiratory SMM events for patients with vs without SARS-CoV-2 infection were similar for the wild-type strain (OR, 2.16 [95% CI, 1.40-3.27]) and Alpha variant (OR, 1.96 [95% CI, 1.20-3.12]), highest for the Delta variant (OR, 4.65 [95% CI, 2.97-7.29]), and not significantly higher in the Omicron period (OR, 1.21 [95% CI, 0.67-2.08]; P for trend < .001). Conclusions and Relevance: This cohort study found that the SARS-CoV-2 Delta variant was associated with higher rates of SMM events compared with other strains. Given the potential of new strains, these findings underscore the importance of preventive measures.

What is "Value"? Results of a Survey of Cancer Patients and Providers.

BACKGROUND: We measured the importance patients with gastrointestinal cancer and health care providers place on treatment outcomes, quality of life, and costs. METHODS: This cross-sectional survey study was conducted between June 1, 2020 and November 30, 2020. We identified surviving patients who had been treated or were anticipating treatment for pancreatic or gastric cancer at our single institution from January 1, 2000 through January 31, 2020. Surveys assessed the importance patients and providers placed on outcomes, well-being, costs, and experiences. Surveys measured how these values had changed over time. We compared the importance patients and providers place on each of the attributes of value. RESULTS: A total of 383 patients and 164 providers responded. Providers felt experience, emotional well-being, and costs were more important than patients themselves did (all p < 0.05). Patients more commonly reported that survival had become more important to them over time, while providers believed that emotional well-being, experience, and costs had become more important to patients (all p < 0.05). Postoperative patients ranked functional well-being as more important than preoperative patients did (p = 0.031). Patients of lower income and education levels more reported concerns of costs over the course of their care (both p < 0.05). Younger age was associated with concern for direct (r = -0.167, p = 0.004) and indirect costs (r = -0.318, p < 0.001). CONCLUSIONS: Although there are consistencies amongst the views of cancer patients and providers, there remain discordances in the perception of value. Patients' values differed across their treatment and survivorship course. These data demonstrate the importance of accounting for multistakeholder perspectives in assessments of value in health care.

Improved Survival over Time After Resection of Colorectal Liver Metastases and Clinical Impact of Multigene Alteration Testing in Patients with Metastatic Colorectal Cancer.

BACKGROUND: The past 20 years have seen advances in colorectal cancer management. We sought to determine whether survival in patients undergoing resection of colorectal liver metastases (CLM) has improved in association with three landmark advances: introduction of irinotecan- and/or oxaliplatin-containing regimens, molecular targeted therapy, and multigene alteration testing. METHODS: Patients undergoing CLM resection during 1998-2014 were identified and grouped by resection year. The influence of alterations in RAS, TP53, and SMAD4 was evaluated and validated in an external cohort including patients with unresectable metastatic colorectal cancer. RESULTS: Of 1961 patients, 1599 met the inclusion criteria. Irinotecan- and/or oxaliplatin-containing regimens and molecular targeted therapy were used for more than 50% of patients starting in 2001 and starting in 2006, respectively, so patients were grouped as undergoing resection during 1998-2000, 2001-2005, or 2006-2014. Liver resectability indications expanded over time. The 5-year overall survival (OS) rate was significantly better in 2006-2014, vs. 2001-2005 (56.5% vs. 44.1%, P < 0.001). RAS alteration was associated with worse 5-year OS than RAS wild-type (44.8% vs. 63.3%, P < 0.001). However, OS did not differ significantly between patients with RAS alteration and wild-type TP53 and SMAD4 and patients with RAS wild-type in our cohort (P = 0.899) or the external cohort (P = 0.932). Of 312 patients with genetic sequencing data, 178 (57.1%) had clinically actionable alterations. CONCLUSION: OS after CLM resection has improved with advances in medical therapy and surgical technique. Multigene alteration testing is useful for prognostication and identification of potential therapeutic targets.

RAS/TP53 Co-mutation is Associated With Worse Survival After Concurrent Resection of Colorectal Liver Metastases and Extrahepatic Disease.

OBJECTIVE: To determine if tumor genetics are associated with overall survival (OS) after concurrent resection of colorectal liver metastases (CLM) and extrahepatic disease (EHD). SUMMARY BACKGROUND DATA: The prognosis for patients who undergo concurrent resection of CLM/EHD is unclear and the impact of somatic mutations has not been reported. METHODS: Patients undergoing concurrent resection of CLM and EHD from 2007 to 2017 were identified from 2 academic centers. From 1 center, patients were selected from a pre-existing database of patients undergoing cytore-ductive surgery with hyperthermic intraperitoneal chemotherapy. The Kaplan-Meier method was used to construct survival curves, compared using the log-rank test. Multivariable Cox analysis for OS was performed. RESULTS: One hundred nine patients were included. Most common EHD sites included lung (33 patients), peritoneum (32), and portal lymph nodes (14). TP53 mutation was the most common mutation, identified in 75 patients (69%), and RAS/TP53 co-mutation was identified in 31 patients (28%). The median OS was 49 months (interquartile range, 24-125), and 3- and 5-year OS rates were 66% and 44%, respectively. Compared to patients without RAS/ TP53 co-mutation, patients with RAS/TP53 co-mutation had lower median OS: 39 vs. 51 months ( P = 0.02). On multivariable analysis, lung EHD [hazard ratio (HR), 0.7; 95% confidence intervals (CI), 0.3-1.4], peritoneal EHD (HR, 2.2; 95% CI, 1.1-4.2) and RAS/TP53 co-mutation (HR, 2.8; 95% CI, 1.1-7.2) were independently associated with OS. CONCLUSIONS: RAS/TP53 co-mutation is associated with worse OS after concurrent CLM/EHD resection. Mutational status and site of EHD should be included in the evaluation of patients considered for concurrent resection.

Development of a patient-reported outcome tool for assessing symptom burden during perioperative care in liver surgery: The MDASI-PeriOp-Hep.

PURPOSE: Based on the MD Anderson Symptom Inventory (MDASI), we developed a Patient-reported outcomes tool for hepatectomy perioperative care (MDASI-PeriOp-Hep). METHODS: To establish the content validity, we generated PeriOp-Hep-specific candidate items from qualitative interviews of patients (n = 30), and removed items that lacked clinical relevance on the basis of input from panels of patients, caregivers, and clinicians. The psychometric properties of the MDASI-PeriOp-Hep were validated (n = 150). The cognitive debriefing and clinical interpretability were assessed to confirm the ease of comprehension, relevance, and acceptability of the tool. RESULTS: Five symptoms specific to hepatectomy (abdominal bloating, tightness, or fullness; abdominal cramping; muscle weakness, instability, or vertigo; constipation; and incisional tightness) were identified as module items to form the MDASI-PeriOp-Hep. The Cronbach αs for symptoms and for interference were 0.898 and 0.861, respectively. The test-retest reliability was 0.887 for all 18 symptom severity items. Compared to other commonly used tools, correlation of MDASI-PeriOp-Hep scores to performance status (all, P < 0.001) and to the phase of perioperative care confirmed known-group validity. Convergent validity was excellent against other standard Patient-reported outcomes tools. Cognitive debriefing demonstrated that the MDASI-PeriOp-Hep was an easy to use and understandable tool. CONCLUSIONS: For integrating patient-reported outcomes in perioperative patient care, a procedure-specific tool is desirable. The MDASI-PeriOp-Hep is a valid, reliable, concise tool for measuring symptom severity and functional interference in patients undergoing liver surgery.

Preliminary Analysis of Liquid Biopsy after Hepatectomy for Colorectal Liver Metastases.

BACKGROUND: Liquid biopsies are increasingly tested in patients with colorectal cancer to assess tumor burden, response to therapy, and prognosis. The significance of liquid biopsy results after resection of colorectal liver metastases (CLMs) is not well-defined. STUDY DESIGN: Sixty-three patients undergoing CLM resection between 2016 and 2018 had plasma drawn postoperatively for liquid biopsy evaluation. Next-generation sequencing analysis was performed to detect somatic mutations in 70 genes. RESULTS: Liquid biopsy after CLM resection was positive in 42 of 63 patients (67%). Eleven patients (18%) had 1 gene mutation, 14 patients (22%) had 2 to 3 mutations, and 17 patients (27%) had 4 or more mutations. The most common mutation was APC, detected in 32 patients (76%), followed by TP53 (74%) and KRAS (38%). Two-year overall survival rate from date of liver resection was significantly worse among patients with a positive liquid biopsy (70% vs 100%; p = 0.005), particularly for those with 4 or more gene mutations detected, whose 2-year overall survival rate was 41%. Sixteen of the 63 patients underwent serial liquid biopsies, resulting in 100 liquid biopsies with matched serum CEA and CT scan results. Metastases were identified in 74 CT scans, which correlated with positive liquid biopsy in 77% of samples (p < 0.001) and CEA > 3 ng/mL in 45% of samples (p < 0.22). CONCLUSIONS: Liquid biopsy results provide information about disease burden and prognosis that is complementary to serum CEA and CT imaging. A positive liquid biopsy after CLM resection is associated with worse overall survival, particularly when multiple gene mutations are detected.

Sustained reduction in discharge opioid volumes through provider education: Results of 1168 cancer surgery patients over 2 years.

BACKGROUND: An opioid reduction education program to decrease discharge opioid prescriptions was initiated in our Department of Surgical Oncology. The study's aim was to measure the results and sustainability of these interventions 1 year later. METHODS: This prospective quality improvement project identified patients undergoing resection in five index tumor sites (peritoneal surface, sarcoma, stomach, pancreas, liver) at a high-volume cancer center. Patients were grouped into pre-education (PRE: July 2017-July 2018) and posteducation (POST: September 2018-July 2019) periods, before and after departmental education talks and videos in August 2018. Opioids were converted to oral morphine equivalents (OME) to compare the groups. RESULTS: Of 1168 evaluable patients (PRE 646, 55%; POST 522, 45%), the median last-24-h inpatient OME was 15 mg in PRE patients and 10 mg in POST patients (p < .001). Median discharge OME decreased from 200 mg in PRE to 100 mg in POST patients (p < .001). The frequency of patients with zero discharge opioids increased from 11% to 19% (p < .001). This discharge OME reduction amounted to 52,200 mg OME saved, or the equivalent of 6960 5-mg oxycodone pills not disseminated. CONCLUSIONS: A perioperative opioid reduction education program targeted to providers halved discharge OME, with sustained reductions 1 year later.

Robotic Completion Radical Cholecystectomy with Fluorescence Guidance.

The application of minimally invasive surgery (MIS) techniques in the treatment of hepatobiliary malignancies offers advantages of shorter length of stay, quicker functional recovery, and decreased need for postoperative opioids. However, MIS completion radical cholecystectomy for incidentally diagnosed gallbladder cancer can be challenging due to a reoperative field and lack of tactile feedback. This video demonstrates the utility of the robotic platform and highlights the ways in which it assists surgeons in overcoming these limitations. These include (1) versatile wristed instruments and excellent visualization that facilitate a thorough regional lymphadenectomy; and (2) built-in fluorescence imaging technology that can be used with intravenous indocyanine green (ICG) to confirm porta hepatis anatomy in a reoperative field. ICG pharmacokinetics enable fluorescence angiography 15-20 s after ICG injection and fluorescence cholangiography 15-20 min after ICG injection as the dye accumulates in the biliary system. Systematic and intentional application of these techniques allows for the safe performance of robotic completion radical cholecystectomy following sound oncologic principles, with excellent perioperative outcomes.

Developing a Value Framework: Utilizing Administrative Data to Assess an Enhanced Care Initiative.

BACKGROUND: There remains no tool to quantify the total value of comparative processes in health care. Hospital administrative data sets are emerging as valuable sources to evaluate performance. Thus, we use a framework to simultaneously assess multiple domains of value associated with an enhanced recovery initiative using national administrative data. MATERIALS AND METHODS: Risk-stratified clinical pathways for patients undergoing pancreatic surgery were implemented in 2016 at our institution. We used a national administrative database to characterize changes in value associated with this initiative. Value metrics assessed included in-hospital mortality, complication rates, length of stay (LOS), 30-day readmission rates, and institutional costs. We compared our performance with other hospitals both before and after implementation of the pathways. Metrics were graphed on radar charts to assess overall value. RESULTS: 22,660 cases were assessed. Comparing 75 cases at our institution and 5520 cases at all other hospitals before pathway implementation, mean in-hospital LOS was 9.6 versus 10.8 d, in-hospital mortality was 0.0% versus 1.9%, mean costs were $23,585 versus $21,387, 30-day readmission rates were 1.3% versus 7.4%, and complication rates were 8.0% versus 11.2%, respectively. Comparing 334 cases at our institution and 16,731 cases at all other hospitals after pathway implementation, mean in-hospital LOS was 7.7 versus 10.3 d, in-hospital mortality was 0.3% versus 1.6%, mean costs were $19,428 versus $22,032, 30-day readmission rates were 6.6% versus 7.5%, and complication rates were 6.3% versus 10.3%, respectively. Notably, LOS and institutional costs were reduced at our institution after implementation of the enhanced clinical care pathways. Our costs were higher than comparators before implementation, but lower than comparators after implementation. CONCLUSIONS: Herein, we used an analytic framework and used national administrative data to assess the value of an enhanced care initiative as benchmarked with data from other hospitals. We thus illustrate how to identify and measure opportunities for targeted improvements in health care delivery. We also recognize the limitations of the use of administrative data in a comprehensive assessment of value in health care.

Time to Rethink Upfront Surgery for Resectable Intrahepatic Cholangiocarcinoma? Implications from the Neoadjuvant Experience.

BACKGROUND: While surgery is a mainstay of curative-intent treatment for patients with intrahepatic cholangiocarcinoma (IHC), the role of neoadjuvant therapy (NT) has not been well-established. We sought to describe trends in NT utilization, characterize associated factors, and evaluate association with overall survival (OS). METHODS: Retrospective cohort study of 4456 surgically resected IHC patients within National Cancer Data Base (2006-2016). NT included chemotherapy alone and/or (chemo)radiation. Descriptive statistics used to describe the cohort. Multivariable hierarchical logistic regression models were used to examine factors associated with NT administration. Analyses conducted comparing OS among upfront surgery patients and NT patients using propensity matching using nearest-neighbor methodology and adjustment using inverse probability of treatment weighting (IPTW). Association between NT and risk of death evaluated using multivariable Cox shared frailty modeling. RESULTS: Utilization of NT did not significantly increase over time (11%-2006 to 16%-2016, trend test p = 0.07) but did increase among patients with clinical nodal involvement (cN+, 13% to 36%, p = 0.002). Factors associated with NT use include cN+ disease (odds ratio [OR] 1.68, 95% confidence interval [CI] 1.31-2.15) and advanced clinical T stage: T2 (OR 1.65, 95% CI 1.33-2.06); T3 (OR 1.51, 95% CI 1.13-2.02). After propensity matching, NT associated with a 23% decreased risk of death relative to upfront surgery (hazard ratio [HR] 0.77, 95% CI 0.61-0.97). Findings were similar after IPTW (HR 0.83, 95% CI 0.78-0.88). CONCLUSIONS: NT is increasingly used for the management of IHC patients with characteristics indicating aggressive tumor biology and is associated with decreased risk of death. These data suggest need for prospective studies of NT in management of patients with potentially resectable IHC.

Two-Stage Hepatectomy for Bilateral Colorectal Liver Metastases: A Multi-institutional Analysis.

BACKGROUND: Two-stage hepatectomy (TSH) is an important tool in the management of bilateral colorectal liver metastases (CRLM). This study sought to examine the presentation, management, and outcomes of patients completing TSH in major hepatobiliary centers in the United States (US). METHODS: A retrospective review from five liver centers in the US identified patients who completed a TSH procedure for bilateral CRLM. RESULTS: From December 2000 to March 2016, a total of 196 patients were identified. The majority of procedures were performed using an open technique (n = 194, 99.5%). The median number of tumors was 7 (range 2-33). One-hundred and twenty-eight (65.3%) patients underwent portal vein embolization. More patients received chemotherapy prior to the first stage than chemotherapy administration preceding the second stage (92% vs. 60%, p = 0.308). Median overall survival (OS) was 50 months, with a median follow-up of 28 months (range 2-143). Hepatic artery infusion chemotherapy was administered to 64 (32.7%) patients with similar OS as those managed without an infusion pump (p = 0.848). Postoperative morbidity following the second-stage resection was 47.4%. Chemotherapy prior to the second stage did not demonstrate an increased complication rate (p = 0.202). Readmission following the second stage was 10.3% and was associated with a decrease in disease-free survival (p = 0.003). OS was significantly decreased by positive resection margins and increased estimated blood loss (EBL; p = 0.036 and p = 0.05, respectively). CONCLUSION: This is the largest TSH series in the US and demonstrates evidence of safety and feasibility in the management of bilateral CRLM. Outcomes are influenced by margin status and operative EBL.

Overall Body Composition and Sarcopenia Are Associated with Poor Liver Hypertrophy Following Portal Vein Embolization.

PURPOSE: To explore whether body composition and/or sarcopenia are associated with liver hypertrophy following portal vein embolization (PVE) in patients with colorectal liver metastases (CLM). METHODS: Patients with CLM who underwent right PVE prior to a planned right hepatectomy were identified from the institutional liver database from 2004 to 2014. Patients were excluded due to previous liver-directed therapy/hepatectomy, right PVE + segment IV embolization, or planned 2-stage hepatectomy. Advanced imaging software was used to measure body compartment volumes (cm2), which were standardized to height (m2) to create an index: skeletal muscle index (SMI), subcutaneous adipose index (SAI), and visceral adipose index (VAI). SMI, gender, and body mass index (BMI) were used to define sarcopenia. The main outcome of interest was hypertrophy of the future liver remnant (FLR) following PVE, which was reported as degree of hypertrophy (DH) and kinetic growth rate (KGR). RESULTS: Patients were evenly divided into three KGR groups: lower third (KGR:0.7-2.0%), middle third (KGR:2.0-4.1%), and upper third (KGR:4.2-12.3%). Patients in the lower third KGR group had a lower VAI (31.0 vs 53.0 vs 54.5 cm2/m2, p = 0.042) and were more commonly sarcopenic (60%) compared to the upper third (20%, p = 0.025). Eighteen patients (40%) met criteria for sarcopenia. Sarcopenic patients had a lower VAI (29.1 vs 57.4 cm2/m2, p = 0.004), lesser degree of hypertrophy (8.3% vs 15.2%, p = 0.009), and lower KGR (2.0% vs 4.0%, p = 0.012). CONCLUSION: Sarcopenia and associated body composition indices are strongly associated with clinically relevant impaired liver regeneration, which may result in increased liver-specific complications following hepatectomy for CLM.

Alteration of FBXW7 is Associated with Worse Survival in Patients Undergoing Resection of Colorectal Liver Metastases.

BACKGROUND: For patients undergoing resection of colorectal liver metastases (CLMs), the prognostic role of somatic gene alterations is increasingly recognized. F-box/WD repeat-containing protein 7 (FBXW7) is a tumor suppressor gene found in approximately 10% of patients with colorectal cancer. The aim of this study is to assess the association of FBXW7 with overall survival after CLM resection. METHODS: Patients who underwent initial CLM resection during 2001-2016 and had genetic sequencing data were studied. Risk factors for overall survival (OS) were evaluated with Cox proportional hazards models using backward elimination. RESULTS: Of 2045 patients who underwent CLM resection during the study period, 476 were included. The majority (90.5%) underwent prehepatectomy chemotherapy. A total of 27 patients (5.7%) had FBXW7 alteration, along with 240 (50.4%) RAS, 337 (70.8%) TP53, 51 (10.7%) SMAD4, and 27 (5.7%) BRAF. Cox proportional hazards model analyses including 5 somatic gene alteration status and 12 clinicopathologic factors revealed FBXW7(hazard ratio [HR] 1.99, P = 0.015), BRAF (HR 2.47, P = 0.023), RAS (HR 2.42, P < 0.001), TP53 (HR 2.00, P < 0.001), and SMAD4 alterations (HR 1.90, P = 0.004) as significantly associated with OS, together with three clinicopathologic factors, prehepatectomy chemotherapy > 6 cycles (HR 1.51, P = 0.021), number of CLM (HR 1.05, P = 0.007), and largest liver metastasis diameter (HR 1.07, P = 0.023). The covariate-adjusted 5-year OS was significantly lower in patients with FBXW7 alteration than in patients with FBXW7 wild-type (40.4% vs.59.4%, P = 0.015). CONCLUSIONS: FBXW7 alterations are associated with worse survival after CLM resection. The information on multiple somatic gene alterations is imperative for risk stratification and patient selection for CLM resection.

A New Surveillance Algorithm After Resection of Colorectal Liver Metastases Based on Changes in Recurrence Risk and RAS Mutation Status.

BACKGROUND: The optimal surveillance strategy after resection of colorectal liver metastases (CLM) is unknown. We evaluated changes in recurrence risk after CLM resection and developed a surveillance algorithm. METHODS: Patients undergoing CLM resection during 1998 to 2015 were identified from a prospectively compiled database and analyzed if they had the potential for follow-up longer than the longest observed time to recurrence in this cohort. Changes in recurrence risk and risk factors for recurrence were evaluated. All statistical tests were 2-sided. RESULTS: Among 2,105 patients who were initially identified and underwent CLM resection, the latest recurrence was observed at 87 months; 1,221 consecutive patients from 1998 through 2011 with the potential for at least 87 months of follow-up were included. The risk of recurrence was highest at 0 to 2 years after CLM resection, lower at 2 to 4 years after CLM resection, and steadily lower after 4 years after CLM resection. Factors associated with increased recurrence risk at the time of surgery were primary lymph node metastasis (hazard ratio [HR], 1.54; 95% CI, 1.21-1.97; P<.001), multiple CLM (HR, 1.31; 95% CI, 1.06-1.63; P=.015), largest liver metastasis diameter >5 cm (HR, 1.64; 95% CI, 1.23-2.19; P<.001), and RAS mutation (HR, 1.29; 95% CI, 1.04-1.59; P=.020). In patients without recurrence at 2 years, the only factor still associated with increased recurrence risk was RAS mutation. In those patients, the recurrence rate at 4 years was 59.3% in patients with RAS mutation versus 27.8% in patients with RAS wild-type (P=.019). CONCLUSIONS: For patients who have undergone CLM resection, we propose surveillance every 3 to 4 months during years 0 to 2, every 3 to 4 months (if mutant RAS) versus every 4 to 6 months (if RAS wild-type) during years 2 to 4, and every 6 to 12 months if recurrence-free at 4 years.