Patient preferences and predicted relative uptake for targeted therapies in metastatic colorectal cancer: a discrete choice experiment.

OBJECTIVE: Ras wild-type metastatic colorectal cancers (mCRC) may be treated with anti-vascular endothelial growth factor (VEGF) or anti-epidermal growth factor receptor (EGFR) agents. We aim to estimate patients' preferences for mCRC treatment and relative importance of cost, efficacy improvement, avoidance of side effects and therapy convenience, and relative uptake between profiles that resemble Bevacizumab (anti-VEGF) and Cetuximab (anti-EGFR), two commonly prescribed mCRC targeted therapies. METHODS: Discrete choice experiment (DCE) was administered to English- or Chinese-speaking Stage 2 or 3 colon cancer patients at the National Cancer Centre Singapore. DCE attributes comprise progression-free survival (PFS), severity of acne-like skin rashes, severity of bleeding, out-of-pocket cost per month and frequency of drug administration. Mixed logit model was used to calculate preference weights for all attribute levels. Subgroup analyses were conducted by interacting attribute levels with selected respondent characteristics. Relative uptake rates for various medication scenarios were studied. RESULTS: 169 respondents aged 61.5 ± 10.5 years completed the survey. They placed the greatest weight on cost, followed by bleeding and skin rashes, then PFS and finally frequency of drug administration. This was similarly observed in the subgroup analyses. A scenario with shorter PFS but less severe side effects has a slightly higher relative uptake at 55%. One quarter of respondents reported that they would not take the treatment they preferred in the choice task. CONCLUSION: Patients were willing to trade off some degree of efficacy to avoid certain severity of side effects. It is therefore crucial for patients and physicians to discuss patients' preferences and circumstances to understand which attributes are more important, as well as patients' views on the trade-offs between treatment benefits and risks.

Prediction of overall survival following colorectal cancer surgery in elderly patients.

BACKGROUND: With advanced age and chronic illness, the life expectancy of a patient with colorectal cancer (CRC) becomes less dependent on the malignant disease and more on their pre-morbid condition. Justifying major surgery for these elderly patients can be challenging. An accurate tool demonstrating post-operative survival probability would be useful for surgeons and their patients. AIM: To integrate clinically significant prognostic factors relevant to elective colorectal surgery in the elderly into a validated pre-operative scoring system. METHODS: In this retrospective cohort study, patients aged 70 and above who underwent surgery for CRC at Singapore General Hospital between 1 January 2005 and 31 December 2012 were identified from a prospectively maintained database. Patients with evidence of metastatic disease, and those who underwent emergency surgery or had surgery for benign colorectal conditions were excluded from the analysis. The primary outcome was overall 3-year overall survival (OS) following surgery. A multivariate model predicting survival was derived and validated against an equivalent external surgical cohort from Kyungpook National University Chilgok Hospital, South Korea. Statistical analyses were performed using Stata/MP Version 15.1. RESULTS: A total of 1267 patients were identified for analysis. The median post-operative length of stay was 8 [interquartile range (IQR) 6-12] d and median follow-up duration was 47 (IQR 19-75) mo. Median OS was 78 (IQR 65-85) mo. Following multivariate analysis, the factors significant for predicting overall mortality were serum albumin < 35 g/dL, serum carcinoembryonic antigen ≥ 20 µg/L, T stage 3 or 4, moderate tumor cell differentiation or worse, mucinous histology, rectal tumors, and pre-existing chronic obstructive lung disease. Advanced age alone was not found to be significant. The Korean cohort consisted of 910 patients. The Singapore cohort exhibited a poorer OS, likely due to a higher proportion of advanced cancers. Despite the clinicopathologic differences, there was successful validation of the model following recalibration. An interactive online calculator was designed to facilitate post-operative survival prediction, available at http://bit.ly/sgh_crc. The main limitation of the study was selection bias, as patients who had undergone surgery would have tended to be physiologically fitter. CONCLUSION: This novel scoring system generates an individualized survival probability following colorectal resection and can assist in the decision-making process. Validation with an external population strengthens the generalizability of this model.

Analytical Validation of Multiplex Biomarker Assay to Stratify Colorectal Cancer into Molecular Subtypes.

Previously, we classified colorectal cancers (CRCs) into five CRCAssigner (CRCA) subtypes with different prognoses and potential treatment responses, later consolidated into four consensus molecular subtypes (CMS). Here we demonstrate the analytical development and validation of a custom NanoString nCounter platform-based biomarker assay (NanoCRCA) to stratify CRCs into subtypes. To reduce costs, we switched from the standard nCounter protocol to a custom modified protocol. The assay included a reduced 38-gene panel that was selected using an in-house machine-learning pipeline. We applied NanoCRCA to 413 samples from 355 CRC patients. From the fresh frozen samples (n = 237), a subset had matched microarray/RNAseq profiles (n = 47) or formalin-fixed paraffin-embedded (FFPE) samples (n = 58). We also analyzed a further 118 FFPE samples. We compared the assay results with the CMS classifier, different platforms (microarrays/RNAseq) and gene-set classifiers (38 and the original 786 genes). The standard and modified protocols showed high correlation (> 0.88) for gene expression. Technical replicates were highly correlated (> 0.96). NanoCRCA classified fresh frozen and FFPE samples into all five CRCA subtypes with consistent classification of selected matched fresh frozen/FFPE samples. We demonstrate high and significant subtype concordance across protocols (100%), gene sets (95%), platforms (87%) and with CMS subtypes (75%) when evaluated across multiple datasets. Overall, our NanoCRCA assay with further validation may facilitate prospective validation of CRC subtypes in clinical trials and beyond.

Author Correction: Reference component analysis of single-cell transcriptomes elucidates cellular heterogeneity in human colorectal tumors.

In the version of the article published, the author list is not accurate. Igor Cima and Min-Han Tan should have been authors, appearing after Mark Wong in the author list, while Paul Jongjoon Choi should not have been listed as an author. Igor Cima and Min-Han Tan both have the affiliation Institute of Bioengineering and Nanotechnology, Singapore, Singapore, and their contributions should have been noted in the Author Contributions section as "I.C. preprocessed Primary Cell Atlas data with inputs from M.-H.T." The following description of the contribution of Paul Jongjoon Choi should not have appeared: "P.J.C. supported the smFISH experiments." In the 'RCA: global panel' section of the Online Methods, the following sentence should have appeared as the second sentence, "An expression atlas of human primary cells (the Primary Cell Atlas) was preprocessed similarly to in ref. 55," with new reference 55 (Cima, I. et al. Tumor-derived circulating endothelial cell clusters in colorectal cancer. Science Transl. Med. 8, 345ra89, 2016).

Systematic review and meta-analysis of the use of serum procalcitonin levels to predict intra-abdominal infections after colorectal surgery.

PURPOSE: There has been much recent interest in the use of procalcitonin (PCT) as a marker of intra-abdominal infection (IAI) following colorectal surgery. However, the literature remains divided on the value of PCT in this setting. This meta-analysis aims to evaluate the value of PCT in predicting IAI after colorectal surgery. METHODS: Systemic literature search was performed using MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) and the Cochrane Database of Systematic Reviews to identify studies evaluating the diagnostic accuracy of PCT as a predictor for detecting IAI on postoperative days (POD) 3 to 5 following colorectal surgery. A meta-analysis was performed using random effect model and pooled predictive parameters as well as cut-off values for POD 3 to 5 were derived. RESULTS: Eight studies consisting 1629 patients were included. The pooled prevalence of IAI was 5.7% on POD 3, 9.7% on POD 4, and 6.3% on POD 5. The pooled AUC for POD 3 to 5 were 0.83 (95% CI 0.78-0.88), 0.79 (95% CI 0.64-0.93), and 0.94 (95% CI 0.91-0.97), respectively. The derived PCT cut-off values were 1.45 ng/ml on POD 3, 1.28 ng/ml on POD 4, and 1.26 ng/ml on POD 5. PCT had the highest diagnostic capability on POD 5 with diagnostic odds ratio of 32.9 (95% CI 15.01-69.88), sensitivity of 0.78 (95% CI 0.65-0.89), and specificity of 0.88 (95% CI 0.85-0.90). CONCLUSIONS: PCT is a useful diagnostic predictor of IAI after colorectal surgery. It has the greatest diagnostic accuracy on POD 5 and can help guide safe discharge of patients after colorectal surgery.

A Novel Derivation Predicting Survival After Primary Tumor Resection in Stage IV Colorectal Cancer: Validation of a Prognostic Scoring Model and an Online Calculator to Provide Individualized Survival Estimation.

BACKGROUND: A prognostic scoring model has been devised previously to predict survival following primary tumor resection in patients with metastatic colorectal cancer and unresectable metastases. This has yet to be validated. OBJECTIVE: The main objectives of this study are to validate the proposed prognostic scoring model and create an interactive online calculator to estimate an individual's survival after primary tumor resection. DESIGN: Clinical data and survival outcomes of patients were extracted from a prospectively maintained database. Patients were categorized into good, moderate, or poor survivor groups based on the previously proposed scoring algorithm. Discrimination was assessed and recalibration was performed, with the recalibrated model implemented as an interactive Web application to provide individualized survival probability. SETTINGS: This study was conducted at a tertiary referral center. PATIENTS: The study included 324 consecutive patients with metastatic colorectal carcinoma and unresectable metastases who underwent primary tumor resection between January 2008 and December 2013. MAIN OUTCOME MEASURES: The primary outcome measured was overall survival. RESULTS: Three hundred twenty-four patients were included in the study. Median survival in the good, moderate, and poor prognostic groups was 56.8, 25.7, and 19.9 months (log rank test, p = 0.003). The κ statistic was 0.638 and RD was 0.101. Significant differences in survival were found between the moderate and good prognostic groups (HR, 2.79; 95% CI, 1.51-5.15; p = 0.001) and between poor and good prognostic groups (HR, 4.12; 95% CI, 1.98-8.55; p < 0.001). The model was implemented as an interactive online calculator to provide individualized survival estimation after primary tumor resection (http://bit.ly/Stage4PrognosticScore). LIMITATIONS: Selection bias and single-center data preclude the generalizability of the proposed model. Information regarding the severity or likelihood of developing symptoms from the primary tumor were also not accounted for in the prognostic scoring model proposed. CONCLUSIONS: The prognostic scoring model provides good prognostic stratification of survival after primary tumor resection and may be a useful tool to predict survival after primary tumor resection. See Video Abstract at http://links.lww.com/DCR/A330.

Reference component analysis of single-cell transcriptomes elucidates cellular heterogeneity in human colorectal tumors.

Intratumoral heterogeneity is a major obstacle to cancer treatment and a significant confounding factor in bulk-tumor profiling. We performed an unbiased analysis of transcriptional heterogeneity in colorectal tumors and their microenvironments using single-cell RNA-seq from 11 primary colorectal tumors and matched normal mucosa. To robustly cluster single-cell transcriptomes, we developed reference component analysis (RCA), an algorithm that substantially improves clustering accuracy. Using RCA, we identified two distinct subtypes of cancer-associated fibroblasts (CAFs). Additionally, epithelial-mesenchymal transition (EMT)-related genes were found to be upregulated only in the CAF subpopulation of tumor samples. Notably, colorectal tumors previously assigned to a single subtype on the basis of bulk transcriptomics could be divided into subgroups with divergent survival probability by using single-cell signatures, thus underscoring the prognostic value of our approach. Overall, our results demonstrate that unbiased single-cell RNA-seq profiling of tumor and matched normal samples provides a unique opportunity to characterize aberrant cell states within a tumor.

Genomics of Hereditary Colorectal Cancer: Lessons Learnt from 25 Years of the Singapore Polyposis Registry.

INTRODUCTION: The Singapore Polyposis Registry (SPR) was established in 1989 in Singapore General Hospital (SGH). The aims were to provide a central registry service to facilitate identification, surveillance and management of families and individuals at high risk of colorectal cancer. MATERIALS AND METHODS: This is a review of published literature in the department. RESULTS: The registry currently has 253 families with several genetic conditions-93 familial adenomatous polyposis (FAP) families, 138 Amsterdam-criteria positive presumed Lynch syndrome (LS) families, 12 families with Peutz Jeghers syndrome, 2 families with Cowden's syndrome, and 8 families with hereditary mixed polyposis syndrome (HMPS). There are also 169 families with a strong family history of colorectal cancer but no abnormal genes yet identified. In FAP, a diagnostic tool developed has allowed a 94% local APC germline detection rate in FAP families. Knowledge obtained studying the phenotype of FAP patients has allowed better choice of surgery between ileal pouch anal anastomosis (IPAA) against an ileal-rectal anastomosis (IRA). In LS, our review has noted a highly heterogenous mutational spectrum and novel variants made up 46.7% (28/60) of all variants identified in this cohort. This may suggest that our Southeast Asian ethnic groups have distinct mutational variants from Western populations. Pathogenic mutations were only confined to MLH1 and MSH2, and identified in 28.8% of families. CONCLUSION: The impact of predictive gene testing for hereditary cancer risk in clinical practice has allowed evolution of care. Risk-reducing surgery and aggressive surveillance allows reduction in morbidity and mortality of patients. The SPR will continue to grow and improve outcomes in hereditary colorectal cancer patients and families.

Risk prediction score in laparoscopic colorectal surgery training: experience from the English National Training Program.

OBJECTIVE: The overall aim was to develop and validate a risk prediction score for laparoscopic colorectal surgery training cases. BACKGROUND: Published risk prediction scores are not transferable between hospitals because they are derived from a single institution's data and are not designed for use in training situations. METHODS: Cases from the prospectively collected database of the National Training Programme in Laparoscopic Colorectal Surgery, between July 2008 and July 2012, were analyzed. Independent risk factors for conversion were identified by the logistic regression. Converting the odds ratios into integers created a risk prediction score for conversion. The clinical impact of this score was investigated by comparing postoperative complications and the level of trainer input in high- and low-risk cases. To study whether adverse outcomes in predicted high-risk cases occur outside the National Training Programme in Laparoscopic Colorectal Surgery, 2 external data sets were examined. RESULTS: A total of 2341 cases carried out in 42 hospitals were analyzed. Significant risk factors for conversion were body mass index, American Society of Anesthesiology classification, male sex, prior abdominal surgery, and resection type. At a risk score of more than 6, complication rates increased, including mortality (2.9% vs 0.5%, P < 0.001), anastomotic leak (4.3% vs 1.4%, P = 0.002), and a higher level of trainer input (32.2% vs 19.9% of cases, P < 0.001). Analysis of 786 external cases showed that high-risk cases had higher conversion (18.8% vs 7.1%, P < 0.001), overall complication (36.4% vs 15.0%, P < 0.001), and leak rates (4.0% vs 1.3%, P = 0.015). CONCLUSIONS: A risk predication score to facilitate case selection in laparoscopic colorectal surgery training was developed and validated.

Short and long-term outcomes of a randomised controlled trial of vertical periumbilical wound versus transverse left iliac fossa wound for specimen retrieval in laparoscopic anterior resections.

BACKGROUND: The ideal incision for laparoscopic specimen extraction is not known. There has been no randomised study thus far evaluating extraction site in laparoscopic colorectal surgery. The aim of our study was to compare post-operative outcomes, pain scores and quality of life scores of vertical periumbilical (VW) versus transverse left iliac fossa (TW) incisions for specimen extraction in laparoscopic anterior resections. METHODS: Using an assumption of pain score of 5 in the VW group versus pain score of 2 in the TW group, on day one post-operatively, and based on a 80% statistical power of analysis to achieve a statistical difference with reduction in pain scores, the sample size per arm calculated was 16. Forty patients undergoing laparoscopic anterior resection were randomised to VW (n = 20) or TW (n = 20). Primary endpoint was post-operative pain. Secondary endpoints were post-operative outcomes, wound cosmesis using Hollander Cosmesis Score and quality of life assessment using EQ-5D at 2 weeks and 2 months post-operatively. RESULTS: Median pain score on the first post-operative day was 2 in both groups (p = 0.360). There was no significant difference in wound infection rates, operative time or post-operative recovery. Cosmesis scores and EQ-5D scores were also similar in both groups. At a median follow-up of 30 months, the incidence of extraction site incisional hernia was similar. CONCLUSION: Transverse and vertical incisions in laparoscopic colorectal surgery have similar post-operative outcomes, with similar pain scores, cosmesis scores, quality of life scores and incisional hernia rates.

Opportunistic screening for colorectal neoplasia in Singapore using faecal immunochemical occult blood test.

INTRODUCTION: The use of faecal immunochemical occult blood test (FIT) has been reported to decrease mortality from colorectal cancer. The Singapore Cancer Society (SCS) gives out FIT kits to encourage opportunistic screening of colorectal cancer. Any Singapore citizen or permanent resident aged ≥ 50 years is eligible to receive two FIT kits. Participants with at least one positive FIT are referred for further evaluation. We aimed to analyse the results of SCS data from the year 2008. METHODS: The factors evaluated included compliance, positive test rate (PR) and positive predictive value (PPV) of FIT. RESULTS: 20,989 participants received 41,978 kits in 2008. Compliance was 38.9%, with 8,156 participants returning at least one kit. 8% of participants tested positive, and 75% of these test-positive participants agreed to undergo further investigations. 33 participants had colorectal cancers, 45 had advanced polyps (≥ 1 cm) and 90 had polyps < 1 cm. Histologically, 114 polyps were adenomatous, 20 were hyperplastic and 1 was serrated. PPV of colorectal neoplasia for those who underwent further colonoscopy was 34%. Over half of the participants who had only one positive test had colorectal neoplasia. CONCLUSION: PR and PPV of FIT in our study were comparable to that in the literature. However, compliance was low and a quarter of all participants who tested positive refused further investigations. Extensive population education programmes are required to improve compliance and tackle inhibitions among the masses. It is also important to take steps to enhance the cost effectiveness of future screening programmes.

Conventional laparoscopic versus single-incision laparoscopic right hemicolectomy: a case cohort comparison of short-term outcomes in 144 consecutive cases.

BACKGROUND: Single-incision laparoscopic surgery (SILS) is a recent development of minimally invasive surgery for colorectal disease. The literature comparing it against conventional laparoscopic colectomy remains limited. METHODS: A retrospective case-cohort study compared the benefits and outcomes of SILS right hemicolectomy (SRH) with those of conventional laparoscopic right hemicolectomy (LRH). The medical records of consecutive patients from a prospectively collected database were reviewed. Demographic data, operative details, recovery parameters, and details of resected specimens were obtained and analyzed in an intention-to-treat manner. RESULTS: From January 2006 to March 2011, 104 elective LRHs (72 %) and 40 elective SRHs (28 %) were performed. The demographics for these two groups were comparable in terms of gender, age, ethnicity, body mass index (BMI), comorbidities and American Society of Anesthesiology score. As the records showed, 62 % of the LRHs and 57 % of the SRHs were performed for malignancies (p = 0.536). Seven of the LRH cases (7 %) were converted to open procedure, whereas two of the SILS cases (5 %) were converted. Three SILS cases (7 %) were completed with additional laparoscopic ports. The two groups did not differ significantly in terms of wound length, mean operative time, lymph node clearance, or margins of resected specimen. The recovery parameters (pain score, hospital length of stay, and complications rate) also were equivalent between the two groups. CONCLUSION: As a feasible and safe procedure with early postoperative outcomes equivalent to those for LRH, SRH is a suitable alternative. The possible advantages of SILS over conventional laparoscopic surgery may be validated only with randomized controlled trials in the future.

Evaluation of laparoscopic versus open colorectal surgery in elderly patients more than 70 years old: an evaluation of 727 patients.

BACKGROUND: With longer life expectancy, surgeons can expect to operate on older patients. Laparoscopic colorectal (LC) surgery has been demonstrated to be superior to open surgery. Controversy persists, however, regarding benefits of LC in the elderly due to increase in operative time. The aim of our study was to compare short-term outcomes of LC versus open colorectal (OC) surgery in elderly patients. MATERIALS AND METHODS: Patients ≥70 years old that underwent elective LC between 2005 and 2008 were compared with controls who underwent OC. Data was extracted from a prospectively collected database. RESULTS: Seven hundred and twenty-seven patients underwent colorectal resection in this study period (LC n = 225, OC n = 502). The laparoscopic arm was characterised by shorter incisions (LC 6.0 cm vs. OC 12.0 cm, p < 0.001) but longer operating times (LC 125 min vs. OC 85 min, p < 0.001). Median use of narcotics and length of stay were significantly shorter in the laparoscopic group (LC 2 days vs. OC 3 days, p < 0.001 and LC 6 days vs. OC 7 days, p < 0.001, respectively). There was no significant difference in median recovery of bowel function (LC 4 days vs. OC 4 days, p = 0.14) and post-operative morbidity (p = 0.725). Thirty-day mortality was significantly lower in the laparoscopic arm (LC 1.3% vs. OC 4.6%, p = 0.03) CONCLUSION: This is the largest series from a single institution comparing LC and OC in elderly patients. In our series, LC in elderly patients was safe and not associated with a higher morbidity. LC was also associated with less narcotic use and shorter length of stay.

Krukenberg tumors of colorectal origin: a dismal outcome--experience of a tertiary center.

BACKGROUND: Krukenberg tumor (KT) is described as metastases of the ovary usually from a tumor of gastric origin. As colorectal cancer (CRC) is now the most common cancer in Singapore, we are seeing more KT with colorectal origin. PURPOSE: To determine the pattern of presentation of KT from CRC origin in terms of patient demographics, time of onset related to the diagnosis of CRC, presence of elevated serum tumor markers, carcinomatosis peritoneii, and survival of patients. METHODS: A retrospective database review of all patients diagnosed with KT from CRC treated in a specialized colorectal surgery department between August 1992 and March 2004. RESULTS: Twenty-five patients' records were available for analysis. Median age at diagnosis was 53 years old (range: 38-79). Sixteen patients (64%) had ovarian metastasis at the time of diagnosis of the CRC. Eleven patients (44%) had unilateral ovarian involvement. Nineteen patients (76%) had carcinomatosis peritoneii. Serum Carcinoembryonic antigen (CEA) was available for 21 patients, 18 (86%) were raised; serum cancer antigen-125 (CA-125) was available for seven patients, five (71%) were raised. There were 11 mortalities (44%) and all died of the disease. Median time between diagnosis of KT and death was 19 months. The rest of the patients were alive with existence of disease at last follow-up. CONCLUSION: KT is associated with a dismal outcome and poor prognosis. There was 0% disease-free survival. Serum CEA and CA-125 tend to rise in patients with KT. Patients investigated for elevated CA-125 and unilateral ovarian mass should have the diagnosis of colorectal cancer excluded before treatment of ovarian mass.

Laparoscopic versus open right hemicolectomy: a comparison of short-term outcomes.

BACKGROUND: The laparoscopic approach is increasingly becoming the gold standard for colorectal resections. While laparoscopic surgery of the left colon and rectum has been evaluated in many studies, laparoscopic resection of the right colon has not been as widely examined. The aim of this study was to examine the short-term outcomes after laparoscopic right hemicolectomies and to determine if they were superior when compared with those after open resection. PATIENTS AND METHODS: Consecutive cases of laparoscopic right hemicolectomies performed between May 2005 and December 2007, in the Department of Colorectal Surgery, Singapore General Hospital, were compared with a matched series of patients who underwent open surgery. RESULTS: From a total of 37 laparoscopic cases, 36 patients successfully underwent laparoscopic right hemicolectomies. There was one conversion, giving a conversion rate of 2.7%. These 37 patients were compared with 40 patients who underwent open right hemicolectomies. The laparoscopic arm was characterised by shorter length of incisions (5.7 vs. 11.2 cm, p < 0.001) but longer operating times (110.8 vs. 71.6 min, p < 0.001). Mean number of lymph nodes harvested and length of proximal and distal margins were similar in both groups. There were also no significant differences between the groups in terms of narcotic use, recovery of bowel function, length of stay, post-operative morbidity and 30-day mortality. CONCLUSION: Laparoscopic right hemicolectomies are as feasible and safe as the open technique. They confer improved cosmesis with smaller incisions but at the expense of longer operating time.

Brain metastases in colorectal cancers.

BACKGROUND: Although colorectal cancer is the most common cancer in Singapore, brain metastases associated with colorectal primaries are quite rare, with reported incidences ranging from less than 1% to 4%. This is a review of the incidence, presentation, and prognosis of brain secondaries from colorectal primaries in our institution. METHODS: From a prospectively collected database, 4378 patients underwent surgery for colorectal cancers between 1995 and 2003. Patients who developed brain metastases were identified and their records reviewed retrospectively. RESULTS: Twenty-seven patients who developed brain metastases were identified, for an incidence of 0.62%. Seventy-one percent of the patients had a tumor in the rectum or sigmoid; 92.6% of patients had metachronous brain secondaries. The median interval between surgery for the primary tumor and the discovery of a brain secondary was 27.5 months. The lung was the most common site of concurrent metastatic disease, with the discovery of a brain secondary a median of 9.7 months after diagnosis of the lung lesion. All patients were symptomatic. The majority of the patients received nonsurgical treatment for the brain lesion. Median survival after diagnosis of brain secondaries was 2.4 months. CONCLUSIONS: The poor survival of the patients in our series could be due to late diagnosis. It may be recommended that a brain scan be performed to screen for a brain secondary when lung and/or liver metastases are discovered, especially in a patient with a left-sided cancer. This may lead to earlier diagnosis, amenability to surgical treatment, and improved survival and quality of life.