Low Clinical Risk Score Research Articles

Clinical Utility of Genomic Recurrence Risk Stratification in Early, Hormone-Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer: Real-World Experience

BackgroundRNA-based genomic risk assessment estimates chemotherapy benefit in patients with hormone-receptor positive (HR+)/Human Epidermal Growth Factor 2-negative (ERBB2-) breast cancer (BC). It is virtually used in all patients with early HR+/ERBB2- BC regardless of clinical recurrence risk. Patients and methodsWe conducted a retrospective chart review of adult patients with early-stage (T1-3; N0; M0) HR+/ERBB2- BC who underwent genomic testing using the Oncotype DX (Exact Sciences) 21-genes assay. Clinicopathologic features were collected to assess the clinical recurrence risk, in terms of clinical risk score (CRS) and using a composite risk score of distant recurrence Regan Risk Score (RRS). CRS and RRS were compared to the genomic risk of recurrence (GRS). ResultsBetween January 2015 and December 2020, 517 patients with early-stage disease underwent genomic testing, and clinical data was available for 501 of them. There was statistically significant concordance between the 3 prognostication methods (P < 0.01). Within patients with low CRS (n = 349), 9.17% had a high GRS, compared to 8.93% in patients with low RRS (n = 280). In patients with grade 1 histology (n = 130), 3.85% had a high GRS and 68.46% had tumors > 1 cm, of whom only 4.49% had a high GRS. Tumor size > 1cm did not associate with a high GRS. ConclusionGenomic testing for patients with grade 1 tumors may be safely omitted, irrespective of size. Our finds call for a better understanding of the need for routine genomic testing in patients with low grade/low clinical risk of recurrence.

Clinical utility of genomic recurrence risk stratification in early, hormone receptor–positive, human epidermal growth factor receptor 2–negative breast cancer.

546 Background: RNA-based genomic assessment of recurrence risk is used to estimate chemotherapy benefit in patients with hormone-receptor positive (HR+)/Human Epidermal Growth Factor 2-negative ( ERBB2-) breast cancer (BC). While originally validated in patients who met established clinicopathologic guidelines for consideration of adjuvant chemotherapy, it is virtually used in all patients with early HR+/ ERBB2- BC regardless of clinical recurrence risk. Methods: We conducted a retrospective chart review of adult patients with early-stage (T1-3; N0; M0) HR+/ ERBB2- BC who underwent genomic risk assessment of recurrence using the Oncotype DX (Exact Sciences) 21-genes assay, between January 2015 and December 2020. Clinicopathologic features were collected to assess the clinical recurrence risk. A low clinical risk score (CRS) was defined as a tumor size ≤ 3 cm in diameter with histologic grade 1, or ≤ 2 cm with grade 2 or ≤ 1 cm with grade 3. A composite risk score of distant recurrent (RRS), derived from a COX model using data from the SOFT and TEXT trials ( https://rconnect.dfci.harvard.edu/CompositeRiskSTEPP/ ), was also computed for 374 patients for whom clinical data was available. RRS &gt; 1.42 was defined as high. High genomic risk of recurrence was defined as a score (GRS) ≥25. The data was collected under IRB approval. Results: A total of 517 patients with early-stage disease were referred for genomic testing, and clinical data was available for 501 of them. Median age was 69 years (IQR=13), median tumor size 1.03 cm (IQR=0.9), and grade 2 histology (57.49%) was the most common. Results of recurrence risk, using the 3 prognostication methods, are summarized in Table. Within patients with low CRS (n=349), 9.17% had a high GRS, compared to 8.93% in patients with low RRS (n=280). In patients with grade 1 histology (n=130), 3.85% had a high GRS and 68.46% had tumors &gt; 1cm, of whom only 4.49% had a high GRS. Tumor size &gt; 1cm did not associate with a high GRS (Fisher’s Exact test; P=1.00). Conclusions: In patients with early HR+/ ERBB2- BC, &lt;10% of patients with low clinical risk, and &lt;5% of patients with grade 1 tumors, had a high genomic recurrence risk, respectively. Given current NCCN recommendation for testing, our findings raise the question of whether genomic testing for patients with grade 1 tumors can be safely omitted, irrespective of size, and call for a better understanding of the need for routine genomic testing in patients with low grade/low clinical risk of recurrence. [Table: see text]

The metabolic clinical risk score (mCRS) as a new prognostic model for surgical decision in patients with colorectal liver metastases.

e15094 Background: Selection for surgery in patients with colorectal liver metastases (CRLM) remains poorly accurate. We evaluated if baseline metabolic characteristics of CRLM, as assessed by [18]-fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (18FDG-PET/CT), may predict the postoperative outcome in patients operated for CRLM. Methods: In a series of 450 patients operated for CRLM, we retrospectively identified 2 groups: The long-term survival (LTS), as defined by postoperative recurrence-free survival (RFS)≥5 years, and the early relapse groups (ER), as defined by RFS &lt; 1 year. Clinicopathologic characteristics, Clinical Risk Score (CRS) and baseline 18FDG-PET/CT metabolic parameters were analyzed. Baseline 18FDG-PET/CT was performed at the time of diagnosis of CRLM, before any preoperative treatment. Low and high-risk CRS were defined by scores of 0 to 2 and 3 to 5, respectively. Metabolic CRS (mCRS) was implemented, using 1 additional point to the standard CRS when the highest tumor standardized uptake value (SUVmax) and normal liver mean SUV (SUVmean(liver)) ratio was &gt; 4.3. Low and high-risk mCRS were defined by scores of 0 to 2 and 3 to 6, respectively. Results: We analyzed 53 patients. No difference was observed between LTS (n = 23) and ER (n = 30) groups for clinicopathologic parameters related to the primary tumor and CRLM, CRS and rates of low/high risk CRS. All metabolic parameters analyzed, including SUVmax and SUVpeak, at the exception of metabolic tumor volume, were significantly increased in ER group. Median SUVmax/SUVmean(liver) ratio was significantly increased in the ER vs LTS, respectively of 4.2 and 2.8 (p = 0.008). mCRS was significantly higher in ER as compared to LTS patients (p = 0.024), while 61% of the LTS patients had a low-risk mCRS and 73% of the ER patients had a high-risk mCRS (p = 0.023). Conclusions: Baseline 18FDG-PET/CT characteristics demonstrate an increased tumor glucose uptake in patients who rapidly recur after curative-intent surgery for CRLM. The introduction of these data into clinical risk model may represent a new tool to improve selection for surgery in patients with CRLM.

Value of KRAS mutation predicting prognosis of patients with colorectal liver-only metastasis after hepatectomy

Objective To explore the value of KRAS mutation predicting prognosis of patients with colorectal liver-only metastasis after hepatectomy. Methods The retrospective case-control study was conducted. The clinicopathological data of 79 patients with colorectal liver-only metastasis who underwent hepatectomy in the Sun Yat-sen University Cancer Center between October 2010 and October 2016 were collected. KRAS mutation in colorectal cancer tissue was detected by fluorescent quantitative polymerase chain reaction (PCR) and laser flight mass spectrometer. Observation indicators: (1) KRAS mutation; (2) relationship between KRAS mutation and clinicopathological factors of patients with colorectal liver-only metastasis; (3) follow-up and survival situations. Follow-up using outpatient examination and telephone interview was performed to detect recurrence-free survival and overall survival up to June 30, 2017. The relationship between KRAS mutation and clinicopathological factors of patients with colorectal liver-only metastasis was analyzed by the chi-square test or Fisher exact probability. The survival curve and time were respectively drawn and calculated by the Kaplan-Meier method, and COX regression model was used for survival analysis. Results (1) KRAS mutation: 79 patients received KRAS gene detection of surgical tumor tissues, including 54 in wide-type mutation and 25 in mutant-type mutation. Of 25 patients in mutant-type mutation, mutation at codon 12 of KRAS exon 2 was in 21 patients, and GGT>GAT (G12D), GGT>GTT (G12V), GGT>TGT (G12C), GGT>GCT (G12A) and GGT>CGT (G12R) of mutation types were respectively detected in 13, 4, 2 , 1 and 1 patients; mutation at codon 13 of KRAS exon 2 was in 3 patients, with a mutation type of GGC>GAC (G13D); mutation at codon 61 of KRAS exon 3 was in 1 patient, with a mutation type of CAA>CAT (Q61H). (2) Relationship between KRAS mutation and clinicopathological factors of patients with colorectal liver-only metastasis: primary tumor located in right and left hemicolon were detected in 11, 14 patients with mutant-type mutation and 7, 47 patients with wide-type mutation, respectively, with a statistically significant difference (χ2=9.357, P 0.05]. Further analysis: of patients with low clinical risk score (CRS) of Memorial Sloan Caitlin Cancer Center (MSKCC), median recurrence-free survival time was 11.3 months in 17 patients with mutant-type mutation and 23.5 months in 26 patients with wide-type mutation, with a statistically significant difference in recurrence-free survival of patients (HR=2.082, 95%CI: 1.006-4.307, P 0.05). Of patients with high CRS of MSKCC, median recurrence-free survival time and median overall survival time were respectively 5.6 months, 28.7 months in 7 patients with mutant-type mutation and 4.5 months, 36.7 months in 24 patients with wide-type mutation, with no statistically significant difference in recurrence-free and overall survivals (HR=0.402, 1.197, 95%CI: 0.284-1.656, 0.371-3.866, P>0.05). Conclusions KRAS mutation is often detected in patients with right colon cancer. Recurrence-free survival time is obviously reduced in patients with KRAS mutation and low CRS of MSKCC. Key words: Colonic neoplasms; Rectal neoplasms; Liver metastases; Translational medicine; KRAS gene; Gene mutations; Surgical procedures, operative; Prognosis

Perioperative Hepatic Arterial Infusion Pump Chemotherapy Is Associated With Longer Survival After Resection of Colorectal Liver Metastases: A Propensity Score Analysis.

Purpose To investigate whether perioperative hepatic arterial infusion pump chemotherapy (HAI) was associated with overall survival (OS) in patients who had a complete resection of colorectal liver metastases (CLM). Methods Patients who underwent a complete resection of CLM between 1992 and 2012 were included from a single-center prospectively maintained database. All patients who received HAI also received perioperative systemic chemotherapy. Propensity score analysis was used to match patients for seven known prognostic factors. Results A total of 2,368 consecutive patients underwent a complete resection of CLM, with a median follow-up of 55 months. The median OS for patients with HAI (n = 785) was 67 months versus 44 months without HAI (n = 1,583; P < .001), despite more advanced disease in the HAI group. OS at 10 years was 38.0% versus 23.8% without HAI. For patients who received modern systemic chemotherapy (n = 1,442), the median OS was 67 months with HAI and 47 months without HAI ( P < .001). The hazard ratio adjusted by propensity score demonstrated longer OS with HAI: 0.67 (95% CI, 0.59 to 0.76; P < .001). A pronounced difference in median OS was found for patients with node-negative colorectal cancer (129 months with HAI v 51 months without; P < .001) and a low clinical risk score of 0 to 2 points (89 months with HAI v 53 months without; P < .001). Conclusion Patients who received HAI had a median OS of approximately 2 years longer than patients without HAI. The strong association was independent of the use of modern systemic chemotherapy and remained in propensity score analysis. Patients with node-negative primary tumors or a low clinical risk score seemed to benefit most from HAI.

MRNA expression profiles of colorectal liver metastases as a novel biomarker for early recurrence after partial hepatectomy

BackgroundIdentification of specific risk groups for recurrence after surgery for isolated colorectal liver metastases (CRLM) remains challenging due to the heterogeneity of the disease. Classical clinicopathologic parameters have limited prognostic value. The aim of this study was to identify a gene expression signature measured in CRLM discriminating early from late recurrence after partial hepatectomy. MethodsCRLM from two patient groups were collected: I) with recurrent disease ≤12 months after surgery (N = 33), and II) without recurrences and disease free for ≥36 months (N = 30). The patients were clinically homogeneous; all had a low clinical risk score (0–2) and did not receive (neo-) adjuvant chemotherapy. Total RNA was hybridised to Illumina arrays, and processed for analysis. A leave-one-out cross validation (LOOCV) analysis was performed to identify a prognostic gene expression signature. ResultsLOOCV yielded an 11-gene profile with prognostic value in relation to recurrent disease ≤12 months after partial hepatectomy. This signature had a sensitivity of 81.8%, with a specificity of 66.7% for predicting recurrences (≤12 months) versus no recurrences for at least 36 months after surgery (X2 P < 0.0001). ConclusionThe current study yielded an 11-gene signature at mRNA level in CRLM discriminating early from late or no relapse after partial hepatectomy.

17 Striving for a Safe and Streamlined HSTNT Negative Chest Pain Pathway

<h3>Objective</h3> This study aimed to assess whether an initial high-sensitivity troponin (HsTnT) value of &lt;3 ng/l or a negative repeat value (&lt;14 ng/l) at 3 h, could be used in conjunction with a validated cardiac risk score (HEART) and a normal 12 lead ECG to risk-stratify, reassure and discharge patients with low-risk presentations. <h3>Background</h3> Many A&amp;E departments still rely on a 12-hour negative HsTnT result for reassurance. Recent publications have demonstrated that a HsTnT value of 3 ng/l at presentation has a high negative predictive value for ruling out acute coronary syndromes with a &lt;1% chance of major adverse cardiac events (MACE) at 1 year documented in one study. <h3>Methods</h3> In a retrospective cohort study we followed up all patients who presented to the A&amp;E department with an initial negative HsTnT (value &lt;14 ng/l) over a three week period. We calculated a validated cardiac risk score for chest pain presentations (HEART). This was compiled for each patient based on their age, cardiac risk factors and the nature of the chest pain recorded in A&amp;E, as well as by reviewing the serial ECGs taken on that presentation. We reviewed each patient’s clinical records at three months and cross-referenced each form of electronic record to identify and review any subsequent cardiac admissions/investigations over that period. <h3>Results</h3> Of 291 patients 121 (41.6%) were admitted. 2 (0.7%) patients in this group had a raised HsTnT at 12 h and were thus classed as NSTEMIs. Both of these had an abnormal ECG and a HEART score of &gt;4 on arrival to A&amp;E. Of the remaining 119 patients admitted, none (0%) had any MACE at 3 months. 15 of the 119 HsTnT-negative patients underwent inpatient cardiac investigation (angiogram/stress ECHO/exercise tolerance testing/CT coronary angiogram), all of which were negative for significant coronary artery disease. Of the 170 (58.4%) patients discharged from A&amp;E none (0%) have had any MACE at 3 months. 53 of these 170 (31.2%) patients were referred into the Rapid Access Chest Pain Clinic. Of these 53, 10 patients underwent a negative stress echo, 11 patients undertook a negative exercise test and the remainder were discharged following a re-evaluation of their history, risk factors and 12 lead ECG. All 53 have had no MACE at 3 months. <h3>Conclusions</h3> All of the patients in this study who had a negative HsTnT value on arrival to A&amp;E, a normal ECG and a low clinical risk score (HEART score &lt;4) have had no MACE as of three months. Many patients underwent further investigation and all of the results were negative for significant coronary artery disease. The data supports the use these criteria in risk-stratifying, reassuring and discharging such patients in a timely manner. It has been used to develop a new chest pain pathway in our local centre. We plan to evaluate the patients through direct patient contact at 6 months to assess MACE rate and exclude loss to another centre.

The use of neo-adjuvant chemotherapy in patients with resectable colorectal liver metastases: Clinical risk score as possible discriminator

AimThe combination of surgery and chemotherapy (CTx) is increasingly accepted as an effective treatment for patients with colorectal liver metastases (CRLM). However, controversy exists whether all patients with resectable CRLM benefit from perioperative CTx. We investigated the impact on overall survival (OS) by neo-adjuvant CTx in patients with resectable CRLM, stratified by the clinical risk score (CRS) described by Fong et al. MethodsPatients who underwent surgery for CRLM between January 2000 and December 2009 were included. We compared OS of patients with and without neo-adjuvant CTx stratified by the CRS. The CRS includes five prognosticators and defines two risk groups: low CRS (0–2) and high CRS (3–5). Results363 patients (64% male) were included, median age 63 years (IQR 57–70). Prior to resection, 219 patients had a low CRS (neo-adjuvant CTx: N = 65) and 144 patients had a high CRS (neo-adjuvant CTx: N = 88). Median follow-up was 47 months (IQR 25–82). In the low CRS group, there was no significant difference in median OS between patients with and without CTx (65 months (95% CI 39–91) vs. 54 months (95% CI 44–64), P = 0.31). In the high CRS group, there was a significant difference in OS between patients with and without CTx (46 months (95% CI 24–68) vs. 33 month (95% CI 29–37), P = 0.004). ConclusionIn our series, patients with a high CRS benefit from neo-adjuvant CTx. In patients with a low risk profile, neo-adjuvant CTx might not be beneficial.

The clinical risk score predicts the effectiveness of adjuvant chemotherapy for colorectal liver metastasis.

Hepatectomy is the most effective treatment for patients with colorectal liver metastasis (CRLM). However, the procedure is also associated with a high risk of recurrence, and adjuvant chemotherapy for postoperative recurrence remains controversial. We investigated the efficacy of adjuvant chemotherapy for CRLM with the clinical risk score (CRS) proposed by Fong et al. Patients with CRLM who were treated, without preoperative chemotherapy, between 1992 and 2012 were classified as having low CRS (score of 0-1), intermediate CRS (2-3), or high CRS (4-5). The efficacy of adjuvant chemotherapy was retrospectively analyzed for each CRS subgroup. Of the 161 patients who underwent hepatectomy, 100 received adjuvant chemotherapy (group A) and 61 did not (group N). For intermediate CRS, 5-year disease free survival (DFS) was significant different between the groups (group A: n = 61; 33.9% vs. group N: n = 39; 23.2%, P = 0.008) and 5-year overall survival (OS) of group A was higher than group N (53.5 vs. 36.5%, P = 0.048), respectively. For both low CRS and high CRS, 5-year DFS and OS were similar between the groups. Multivariate analysis of DFS identified prognostic factors as major resection for low CRS (P = 0.02) and adjuvant chemotherapy for intermediate CRS (P = 0.015). Similarly, multivariate analysis of OS identified major resection for low CRS (P = 0.05) and adjuvant chemotherapy for intermediate CRS (P = 0.05). High CRS was not identified prognostic factor. Adjuvant chemotherapy for CRLM was effective in intermediate CRS patients. In low CRS patients, adjuvant chemotherapy may not be necessary, but adequate surgical resection is important.

Preoperative FDG-PET-Scan in Patients with Resectable Colorectal Liver Metastases Does Not Improve Overall Survival: A Retrospective Analyses Stratified by Clinical Risk Score

Background: The aim of this study was to determine whether selection with fluorine-18-deoxyglucose positron emission tomography (FDG-PET) imaging would result in an improved outcome in surgically treated patients with curative resection of colorectal liver metastases (CRLM), stratified by the clinical risk score (CRS) of Fong et al. [Ann Surg 1999;230:309-318]. Patients and Methods: Between January 2000 and December 2009, all patients who underwent resection for CRLM from two different university teaching hospitals in the Netherlands were analysed. Patients were stratified by the CRS. Results: In total 613 patients were eligible for analysis. There was no statistical difference in median disease-free survival (DFS) between patients with and without an FDG-PET scan in both low CRS [17 months (95% CI 12-22) vs. 14 months (95% CI 11-17), p = 0.332] and high CRS [14 months (95% CI 7-21) vs. 9 months (95% CI 8-10), p = 0.073]. There was no statistical difference in median overall survival (OS) between patients with and without an FDG-PET scan in both low CRS [64 months (95% CI 54-74) vs. 54 months (95% CI 42-66), p = 0.663] and high CRS [39 months (95% CI 23-55) vs. 41 months (95% CI 34-48), p = 0.903]. Conclusion: The present study could not demonstrate that patients selected by an FDG-PET scan before liver resection, and stratified by CRS, have an improvement in DFS or OS.

NEW STRATEGIES IN LIVER SURGERY FOR IV STAGE METASTATIC COLORECTAL CANCER.

With recent advances in chemotherapy, traditional clinicopathological factors should not be used to exclude otherwise resectable patients from surgery. Pathological or clinical response to chemotherapy has become valuable in determining the treatment for individual patients. Portal vein embolization and two-stage operation with ablative therapy and preoperative chemotherapy should be considered for unresectable liver metastases located in a liver remnant that is at the minimum volume required for survival. The recent E0RTC 40983 trials regarding preoperative chemotherapy for resectable CLM have failed to demonstrate a clear significant advantage. However, patients with a low clinical risk score for the recurrence, such as several metastases of less than 4 cm, and who are fit candidates for liver resection are often offered immediate surgery. Patients at high clinical risk should also be considered for neoadjuvant chemotherapy. One forthcoming and appealing strategy is to adapt postoperative treatment according to tumor response as evaluated by neoadjuvant chemotherapy or by the presence of individual tumor biomarker such as the Kras mutation or singlenucleotide polymorphisms. This could avoid the overtreatment of nonresponsive patients and enable a more tailored approach to treat an individual patient’s disease. The treatment paradigm for CLM is rapidly changing with the development of newer anticancer chemotherapeutic agents.

CT-guided Radiofrequency Ablation as a Salvage Treatment of Colorectal Cancer Hepatic Metastases Developing after Hepatectomy

Purpose To evaluate the clinical outcomes of percutaneous radiofrequency (RF) ablation of colorectal cancer liver metastases (CLMs) that recur after hepatectomy. Materials and Methods From December 2002 to December 2008, 71 CLMs that developed after hepatectomy were ablated in 56 patients. Medical records and imaging were reviewed to determine technique effectiveness/complete ablation (ie, ablation defect covering the entire tumor on 4–6-week postablation computed tomography [CT]), complications, and local tumor progression (LTP) at the site of ablation. LTP-free and overall survival were calculated by using Kaplan–Meier methodology. A modified clinical risk score (CRS) including nodal status of the primary tumor, time interval between diagnoses of the primary tumor and liver metastases, number of tumors, and size of the largest tumor was assessed for its effect on overall survival and LTP. Results Tumor size ranged between 0.5 and 5.7 cm. Complete ablation was documented in 67 of 71 cases (94%). Complications included liver abscess (n = 1) and pleural effusion (n = 1). Median overall survival time was 31 months. One-, 2- and 3-year overall survival rates were 91%, 66%, and 41%, respectively. CRS was an independent factor for overall survival (74% for CRS of 0–2 vs 42% for CRS of 3–4 at 2 y; P = .03) and for LTP-free survival (66% for CRS of 0–2 vs 22% for CRS of 3–4 at 1 y after a single ablation; P <.01). Conclusions CT-guided RF ablation can be used to treat recurrent CLM after hepatectomy. A low CRS is associated with better clinical outcomes.

Randomized comparison between clinical evaluation plus N-terminal pro–B-type natriuretic peptide versus exercise testing for decision making in acute chest pain of uncertain origin

Exercise testing constitutes the usual tool for decision making in chest pain units. This policy implies logistical constrains. Our aim was to evaluate a new strategy, combining a clinical risk score and N-terminal pro-B-type natriuretic peptide (NT-proBNP), in patients presenting to the emergency department with chest pain, without ischemic electrocardiogram changes or troponin elevation. A total of 320 patients were randomized to either usual management, involving exercise testing, or a new strategy combining a clinical risk score and NT-proBNP without exercise testing. In the usual management, discharge decision was guided by the result of exercise test. In the new strategy, those patients with low clinical risk score and NT-proBNP were directly discharged. The primary outcome was hospitalization at the index episode. Secondary outcomes were cardiac events at 1 year. A total of 110 patients (69%) were hospitalized using usual management in comparison with 90 (56%) in the new strategy (P = .03). There were no differences in death or myocardial infarction (n = 11, 6.9% vs n = 6, 3.8%, P = .3) or cardiac events (n = 38, 24% vs n = 28, 18%, P = .2). Revascularizations at the index episode were more frequent under usual management (18% vs 8%, P = .01), although the new strategy was associated with higher rate of planned postdischarge revascularizations (0.6% vs 5%, P = .04). A strategy combining clinical history and NT-proBNP is simpler and reduced initial emergency hospitalizations in patients with chest pain, in comparison with the usual strategy involving exercise testing. Larger studies to assess its impact on long-term hard end points are needed.

Fractional Genomic Alteration Detected by Array-Based Comparative Genomic Hybridization Independently Predicts Survival after Hepatic Resection for Metastatic Colorectal Cancer

Although liver resection is the primary curative therapy for patients with colorectal hepatic metastases, most patients have a recurrence. Identification of molecular markers that predict patients at highest risk for recurrence may help to target further therapy. Array-based comparative genomic hybridization was used to investigate the association of DNA copy number alterations with outcome in patients with colorectal liver metastasis resected with curative intent. DNA from 50 liver metastases was labeled and hybridized onto an array consisting of 2,463 bacterial artificial chromosome clones covering the entire genome. The total fraction of genome altered (FGA) in the metastases and the patient's clinical risk score (CRS) were calculated to identify independent prognostic factors for survival. An average of 30 +/- 14% of the genome was altered in the liver metastases (14% gained and 16% lost). As expected, a lower CRS was an independent predictor of overall survival (P = 0.03). In addition, a high FGA also was an independent predictor of survival (P = 0.01). The median survival time in patients with a low CRS (score 0-2) and a high (> or =20%) FGA was 38 months compared with 18 months in patients with a low CRS and a low FGA. Supervised analyses, using Prediction Analysis of Microarrays and Significance Analysis of Microarrays, identified a set of clones, predominantly located on chromosomes 7 and 20, which best predicted survival. Both FGA and CRS are independent predictors of survival in patients with resected hepatic colorectal cancer metastases. The greater the FGA, the more likely the patient is to survive.