Diagnosis Of Primary Colorectal Cancer Research Articles

Identification of somatic alterations associated with brain metastases from a colorectal origin.

210 Background: Colorectal brain metastases (cBM) confer a devastating prognosis with survival of less than 13 months. Identifying genomic signatures to predict and guide treatment for these patients would be a valuable adjunct. This study evaluated genomic and clinicopathological features specific to cBM. Methods: cBM patients from the MSK-MET cohort were evaluated in comparison to other colorectal cancer patients with extracranial metastases (cOM). Clinicopathologic features and genomic alterations were analyzed with MSK-IMPACT, a targeted DNA sequencing panel for solid tumors and matched blood specimens. We considered mutations, copy number alterations, and fusions. Analyses of genomic features were restricted to microsatellite stable (MSS) patients. q-values were computed using Benjamini-Hochberg correction to account for multiple hypothesis testing. Patient record review identified patients with sequenced matched samples from the primary colorectal tumor and the brain metastases, which were then examined for loss and gain of assessed genetic alterations. Results: Of 130 patients with cBM identified from the cohort, 20 samples were from brain metastases, 52 from the primary CRC, and 58 from other metastatic sites. Average time to diagnosis of cBM was 3.5 years after primary colorectal cancer diagnosis and average time to death was 10 months after cBM diagnosis. Compared to the 3,383 cOM patients, cBM patients had significantly higher rates of both MSS CRC primaries (p<0.001, 122/130 cBM were MSS vs. 3,038/3,382 cOM) and primaries that originated in the rectum (p<0.002, with 38/130 cBM primaries from the rectum vs. 695/3,382 cOM rectal primaries). Somatic alterations in the KRAS, BRCA2, CDK8 and ERCC5 genes were significantly more frequent in patients with cBM compared to cOM patients (all p<0.001) (Table 1). Of the 9 patients who had matched primary and metastatic brain tissue sequenced, KRAS alterations were shared between the primary and brain metastasis in 2/9, ERBB3 and ERCC5 in 2/9, p53 in 6/9, and APC in 6/9 patients. In addition, newly acquired private alterations found only in the brain metastasis samples of matched patients included PIK3RI, ARID5B, NOTCH4, CYLD and SMAD4. Conclusions: We identify new genomic and clinical factors in cBM patients, including somatic alterations in potentially clinically actionable targets. To further explore potential clinical utility, these findings require validation in an independent cBM clinicogenomic dataset.[Table: see text]

Three-dimensional laparoscopic surgery for colorectal cancer: A 2-year follow-up study at Hue Central Hospital

BackgroundLaparoscopic surgery has brought about a revolution in clinical practice since its inception. Using a new generation three-dimensional (3D) HD laparoscopic system can be seen as a beneficial “hybrid” created by fusing two different elements: increased vision quality and the viability and diffusion of laparoscopy. This study aims to determine the surgical outcomes and two-year survival of colorectal cancer patients after 3D laparoscopic surgery. MethodsA prospective study was conducted on 60 patients with a definitive diagnosis of primary colorectal cancer. All patients underwent 3D laparoscopic colorectal resection from January 2020 to December 2021 by a single surgical team. Data were prospectively collected from Hue Central Hospital, including operative parameters and survival time. ResultsThe mean age was 62.0 ± 10.6 years old. D3 lymphadenectomy accounted for most cases (96.7 %). There were no intraoperative complications or conversion to open surgery. The mean operation time was 162.3 ± 25.8 min. Postoperative complications included incisional fluid collection (5 %), wound infection (3.3 %), and drainage site bleeding (1.7 %). The average length of hospital stay was 10.4 ± 4.6 days. Overall survival rate after two years was 93 %. Conclusions3D laparoscopic surgery for radical treatment of colorectal cancer is feasible, effective, and safe. This surgical technique offers a positive prognosis for patients.

Incidence and risk outcomes of second primary malignancy of patients with post-operative colorectal cancer

This study aimed to investigate the incidence and the risk factors of incidence for second primary malignancies (SPMs) onset among survivors diagnosed with colorectal cancer (CRC). A large population-based cohort study was performed. Data of patients diagnosed with CRC was identified and extracted from 8 cancer registries of Surveillance, Epidemiology, and End Results database from January 1990 to December 2017. The outcome of interest was percentage and common sites of SPM onset after primary CRC diagnosis. The cumulative incidence and standardize incidence rates (SIRs) were also reported. Afterwards, we estimated sub-distribution hazards ratios (SHRs) and relative risks (RRs) for SPM occurrence using multivariable competing-risk and Poisson regression models, respectively. A total of 152,402 patients with CRC were included to analyze. Overall, 23,816 patients of all CRC survivors (15.6%) were reported SPM occurrence. The highest proportion of SPMs development after primary CRC diagnosis was second CRC, followed by lung and bronchus cancer among all survivors. Also, CRC survivors were more susceptible to develop second gastrointestinal cancers (GICs). Besides, pelvic cancers were analyzed with a relative high proportion among patients who received RT in comparison to those without RT. The cumulative incidence of all SPMs onset was 22.16% (95% CI: 21.82-22.49%) after near 30-year follow-up. Several factors including older age, male, married status, and localized stage of CRC were related to the high risk of SPMs onset. In treatment-specific analyses, RT was related to a higher cumulative incidence of SPMs occurrence (all SPMs: 14.08% vs. 8.72%; GICs: 2.67% vs. 2.04%; CRC: 1.01% vs. 1.57%; all p < 0.01). Furthermore, the increased risk of SPMs onset was found among patients who received RT than patients within the NRT group (SHR: 1.50, 95% CI: 1.32-1.71), p < 0.01; RR: 1.61, 95% CI: 1.45-1.79, p < 0.01). The present study described the incidence pattern of SPM among CRC survivors and identified the risk factors of the SPM onset. RT treatment for patients diagnosed with CRC may increase the risk of SPMs occurrence. The findings suggest the need for long-term follow-up surveillance for these patients.

Hyperthermic Intraperitoneal Chemotherapy After Cytoreductive Surgery; Experience and Short Term Outcomes

Purpose: Cytoreductive surgery + hyperthermic intraperitoneal chemotherapy is an important treatment option in patients with primary diagnosis of colorectal cancer, ovarian cancer, appendix cancer, gastric cancer (selected cases), malignant peritoneal mesothelioma and peritoneal pseudomyxoma in the presence of peritoneal involvement and resectable lesions limited to the abdomen. In this study, it is aimed to discuss cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy(HIPEC) in the light of literature. Patients and methods: The data of patients who underwent cytoreductive surgery with hyperthermic intraperitoneal chemotherapy between June 2017 and September 2020 at Eskisehir Osmangazi University Medical Faculty Surgical Oncology and Gastroenterology Surgery Departments were analyzed. The study was designed retrospectively, and all patients who were discussed at the oncology council and decided on CRS + HIPEC were included in the study. Results: 31 patients were included in the study. Primary diagnoses of the patients were colorectal cancer in 15 (48%), ovarian cancer in 9 (29%), stomach cancer in 3 (10%), mesothelioma in 2 (7%), appendix cancer in 1 (3%), and also peritoneal pseudomyxoma in 1 (3%). Therapeutic HIPEC was performed in 30 patients, prophylactic HIPEC was performed in 1 patient. Cytoreduction score was 0 in all patients. The median peritoneal cancer index was 15 (7-29). the median number of resected organs was 3(1-6). Stoma formation was performed in 14 patients (45%). During the postoperative 30 days, mortality was observed in 1 patient (3%) and morbidity in 5 patients (16%). Conclusion: The early postoperative mortality and morbidity results which were reported in our study are compatible to those in the literature.

Development of a Fully Automated Method to Obtain Reproducible Lymphocyte Counts in Patients With Colorectal Cancer.

Colorectal cancer (CRC) is the third most common cancer worldwide. Although clinical outcome varies among patients diagnosed within the same TNM stage it is the cornerstone in treatment decisions as well as follow-up programmes. Tumor-infiltrating lymphocytes have added value when evaluating survival outcomes. The aim of this study was to develop a fully automated method for quantification of subsets of T lymphocytes in the invasive margin and central tumor in patients with CRC based on Deep Learning powered artificial intelligence. The study cohort consisted of 163 consecutive patients with a primary diagnosis of CRC followed by a surgical resection. Double-labeling immunohistochemical staining with cytokeratin in combination with CD3 or CD8, respectively, was performed on 1 representative slide from each patient. Visiopharm Quantitative Digital Pathology software was used to develop Application Protocol Packages for visualization of architectural details (background, normal epithelium, cancer epithelium, surrounding tissue), identification of central tumor and invasive margin as well as subsequent quantitative analysis of immune cells. Fully automated counts for CD3 and CD8 positive T cells were obtained in 93% and 92% of the cases, respectively. In the remaining cases, manual editing was required. In conclusion, the development of a fully automated method for counting CD3 + and CD8 + lymphocytes in a cohort of patients with CRC provided excellent results eliminating not only observer variability in lymphocyte counts but also in identifying the regions of interest for the quantitative analysis. Validation of the performance of the Application Protocol Packages including clinical correlation is needed.

SPARCL1 Is a Novel Prognostic Biomarker and Correlates with Tumor Microenvironment in Colorectal Cancer

Background Secreted protein acidic and rich in cysteine-like 1 (SPARCL1) plays an important role in tumor pathogenesis. We aim to evaluate the clinical significance and potential biological roles of SPARCL1 in colorectal cancer (CRC). Methods Datasets from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were downloaded to evaluate the expression levels of SPARCL1 in CRC. Receiver operating characteristic (ROC) curve was constructed to evaluate the diagnostic value of SPARCL1. Then, comprehensive database search was conducted for published clinical studies to explore clinical significance of SPARCL1. In addition, coexpression genes of SPARCL1 were identified through the cBioPortal database and enrichment analysis of SPARCL1 and its coexpression genes were performed by the “clusterProfiler” R package. Finally, the correlations between SPARCL1 and tumor microenvironment scores, tumor-infiltrating immune cells in CRC were determined by “ESTIMATE” and “GSVA” R packages. Results SPARCL1 was significantly downregulated in CRC tissues, and SPARCL1 showed high accuracy for diagnosis of primary CRC in both GEO and TCGA datasets. Pooled results from published clinical studies showed SPARCL1 expression was associated with differentiation (OR = 1.89, 95% CI: 1.38-2.59), tumor stage (OR = 0.47, 95% CI: 0.29-0.77), distant metastasis (OR = 0.53, 95% CI: 0.33-0.84), and overall survival (HR = 0.56, 95% CI: 0.43-0.74). SPARCL1 and its top 300 coexpression genes were involved in several KEGG pathways, such as focal adhesion, cell adhesion molecules, PI3K-Akt signaling pathway, cGMP-PKG signaling pathway, and ECM-receptor interaction. Besides, the SPARCL1 expression was significantly correlated with stromal score, immune score, ESTIMATE score, and diverse immune cells. Conclusion SPARCL1 significantly correlated with clinicopathological features and tumor microenvironment in CRC.

Risk Factors of Colorectal Cancer in Hospitalized Patients in Regional Hospital Durrës

Introduction&#x0D; Colorectal cancer (CRC) is the most common gastrointestinal cancer with an important global health problem. The study aims were to evaluate the risk factors of colorectal cancer in chirurgical ward in Regional Durres Hospital in Albania during two years.&#x0D; Methods&#x0D; We conducted a retrospective cohort study to explore risk factors of Colorectal Cancer at the Surgical ward of the Regional Hospital Durres is the second largest and a referral hospital center in Albania. In this paper we have collected medical records of 79 adults 18 years of age and older with primary diagnosis of CRC admitted to this hospital during the periods January 2009 until to December 2010. Data were analyzed using the statistical package for social science (SPSS) version 23.0. A p &lt; 0.05 was accepted as statistically significant.&#x0D; Results &#x0D; Overall, 79 patients with CRC enrolled in our study, the male (58.2%) was the most predominant gender compared to female (41.8%) with a strong significance between them χ2 =79.0 and p value &lt;0.0001. The average age was 69.43 ±10.6 where the minimum age resulted 42 years old and the maximum 85 years old. Patients between the age group 61-70 years old were 29.1% of CRC cases, them with age group 71-80 years old presented the higher number of CRC 34.2% of cases. A strong significance association has been seen between the age groups and presence of CRC. In multivariate logistic regression we also found a significance association for some of the other risk factor for CRC like gender, aging, marital status, education level BMI and physical activity. The p value in all these risk factor resulted &lt;0.05.&#x0D; Conclusion &#x0D; The prevalence of this malignancy in our study increases after the age of 60 years. Our study findings show that the presence of CRC was in strength association with some of risk factors. But the number of our patients were low, so based on our observations, we suggest future studies should involve a large number of patients and focus on better understanding mechanisms for some of these associations and presence of CRC risk.

Incidence and predictors of brain metastasis in colorectal cancer patients.

Brain metastasis (BM) in colorectal cancer patients is rare and is associated with dismal outcomes. Our study aims to evaluate the incidence and predictors of BM in patients with colorectal cancer. We performed a retrospective analysis (2010-2017) of patients with a primary diagnosis of colorectal cancer (CRC). Patients were stratified into two groups (BM vs. No-BM). Outcome measures were the incidence and predictors of BM. Multivariate logistic regression analysis was performed. A total of 230,806 patients were analyzed. A total of 0.30% (n = 691) of the patients were found to have BM. On multivariate logistics regression, bone (OR: 5.39 [3.36-8.65], p < 0.001), lung (OR: 3.75 [2.67-5.28], < 0.001), and distant node metastasis (OR: 32.75 [20.47-52.41], p < 0.001) were independent predictors of BM. Our study supports the low incidence of brain metastasis in patients with colorectal cancer. A unique set of characteristics is identified to confer an increased risk of brain metastases.

Abstract 569: Correlation of variant allele frequency and mean tumor molecules with tumor burden in patients with solid tumors

Abstract Introduction: Two metrics are commonly used to quantify tumor-specific variants in cell-free DNA (cfDNA): the variant allele frequency (VAF), defined as the ratio of the number of variant alleles to wild-type alleles, and mean tumor molecules (MTM)/mL of plasma. The main difference between the two metrics is that molecular disease levels expressed in MTMs account for the total amount of cfDNA. Changes in cfDNA levels, which occur in response to cytotoxic therapies, surgery, and inflammation, have shown to impact the detection and quantification of tumor variants in plasma, leading to misinterpretation of the test results. Here we sought to explore the relationship between VAF and MTM and evaluate the performance of each metric in monitoring molecular residual disease. Methods: We have analyzed 6569 plasma samples from 3389 patients including patients with primary diagnosis of colorectal cancer (n = 2413), breast (n = 170), pancreatic (n = 132), esophageal (n = 86), lung (n = 60), liver (n = 54), other cancers (n = 474) across multiple settings. ctDNA was quantified using a personalized and tumor-informed (bespoke mPCR NGS) assay. We examined the correlation between MTM and VAF for all ctDNA positive plasma samples (n = 1970) from 1283 patients using log-log regression. For patients with longitudinal plasma time points, further analyses on dynamic changes in MTM and VAF was performed to assess the sample-level discrepancy between the two metrics. Furthermore, the absolute values and the dynamic changes in MTM and VAF levels were plotted and compared against clinical truth based on imaging results and patient outcomes. Results: Across all samples median cfDNA concentrations were 7.9 ng/mL (range: 1.3-381.6 ng/mL). Analysis of all ctDNA positive samples revealed a positive correlation between VAF and MTM, with R2 = 0.91 (slope: 0.86). From 3180 longitudinal plasma samples, we found 2.4% (76/3180) of samples, where changes relative to the previous time point were discordant between MTM and VAF. Interestingly, cfDNA concentrations in these samples were significantly altered. In general, cfDNA levels are representative of intrinsic cell turnover. While VAF is directly related to ctDNA, it is inversely related to cfDNA levels. Increased cfDNA levels were seen in the setting of active cytotoxic therapy, perioperatively, and in the setting of advanced disease, suggesting these settings may be prone for VAF to underestimate the true ctDNA burden. Here we provide evidence that failure of VAF to account for the dynamic changes in cfDNA concentration in plasma may result in misinterpretation of the patient's disease burden. This suggests that in certain indications MTM would be more clinically relevant than VAF. Conclusion: Although both VAF and MTM are highly correlated, our analysis shows when cfDNA levels are significantly altered, MTM/mL provides a more accurate measure of molecular disease burden. Citation Format: Antony Tin, Vasily Aushev, Ekaterina Kalashnikova, Raheleh Salari, Svetalana Shchegrova, Gordon Fehringer, Meenakshi Malhotra, Harini Ravi, Himanshu Sethi, Maxim Brevnov, Bernhard Zimmermann, Angel Rodriguez, Paul R. Billings, Alexey Aleshin. Correlation of variant allele frequency and mean tumor molecules with tumor burden in patients with solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 569.

FDG PET/CT and Colonoscopy Combine Synergistically in Colorectal Cancer Primary Diagnosis.

Aim: Colonoscopy is the standard for primary colorectal cancer (CRC) detection, but is invasive and imperfect. The aim of this study was to assess the accuracy of 18F-fluorodeoxyglucose (FDG) Positron emission tomography/Computed tomography (PET/CT) and colonoscopy in the diagnosis of primary CRC. Methods: A retrospective analysis of all patients identified as undergoing a FDG PET/CT scan and a colonoscopy within six months of each other, with no intervening malignancy treatment, over a 12 month period in a single University teaching hospital. Results: Two hundred and sixty-two patients had FDG PET/CT and colonoscopy within 6 months. 206 were excluded for prior treatment. 56 patients were included, 26 (46%) with confirmed primary CRC tumors and 30 (54%) without. Multivariate logistic regression analysis indicated that CRC diagnosis was more likely when colonoscopy was performed before the FDG PET/CT (Odds Ratio (OR) 21.9 (CI 2.6-183) and when CRC was diagnosed on FDG PET/CT (OR 12.3 (CI 3.0-51.0). The ROC-AUC for FDG PET/CT and colonoscopy was 0.81 (CI 0.70-0.93, p <0.001) and 0.96 (CI 0.90-1.0, p <0.001) respectively. Conclusions: Colonoscopy is very good and FDG PET/CT is good as diagnostic tests for CRC primary diagnosis. Together they facilitated diagnosis in all CRC primaries. PET/CT should be considered in patients’ with incomplete colonoscopy where there is suspicion for CRC primary.

Systematic Review of Neoadjuvant Immunotherapy for Patients With Non–Small Cell Lung Cancer

There is a paucity of robust clinical evidence for the role of neoadjuvant immunotherapy in patients with resectable non-small cell lung cancer. The primary aim of the study was to identify the available data on the feasibility, safety and efficacy of neoadjuvant immunotherapy. A systematic review was conducted using electronic databases. Relevant studies were identified according to predefined selection criteria. Five relevant publications on 4 completed trials were identified. In most studies, >90% of patients were able to undergo surgery within the planned timeframe after neoadjuvant immunotherapy. There was a high incidence of open thoracotomy procedures, either planned or converted from a planned minimally invasive approach. Mortality ranged from 0 to 5%, but none of the reported deaths were considered directly treatment-related. Morbidities were reported according to adverse events related to neoadjuvant systemic therapy, and postoperative surgical complications. Survival outcomes were limited due to short follow-up periods. Major pathologic response ranged from 40.5 to 56.7%, whilst complete pathologic response of the primary tumor ranged from 15 to 33%. Radiological responses were reported according to RECIST criteria and fluorodeoxyglucose-avidity. This systematic review reported safe perioperative outcomes of patients who underwent resection following neoadjuvant immunotherapy. However, there was a relatively high incidence of open thoracotomy procedures, partly due to the technical challenges associated with increased fibrosis and inflammation of tissue, as well as the more advanced stages of disease in patients enrolled in the studies. Future studies should focus on identifying predictors of pathological response.

A Retrospective Study of Administrative Data to Identify Factors Associated with Future Disability Status among Older Colorectal Cancer Survivors

Abstract Disability is associated with loss of independence and early mortality. Currently, only 1–2% of cancer survivors who reported physical limitations received rehabilitation services. It is critical to identify factors associated with the development of disability to guide clinical practice given treatment changes. We aimed to 1) identify demographic and cancer-related characteristics associated with future disability status among older colorectal cancer survivors, and 2) compared the future disability status among cancer and matched non-cancer cohorts. Methods: We conducted a retrospective cohort study using the Texas Cancer Registry-national Medicare linked database. The cancer cohort included Medicare beneficiaries with a primary colorectal cancer diagnosis between 2005 and 2013 (n = 13,229). The non-cancer cohort was identified from a 5% sample of Medicare beneficiaries (n = 11,416). Diagnosis dates from the cancer cohort were used as the index date for the non-cancer cohort. Cohorts were matched 1:1 based on index date, age, and gender. Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals. Disability status was defined according to Davidoff and colleagues using inpatient, outpatient and durable medical equipment claims files, and assessed monthly, beginning 1 month after cancer diagnosis (or index date), continuing until disability, death, end of Medicare continuous enrollment, or end of study. Results: Factors that were significantly associated with disability status in the cancer cohort were age (HR = 3.50 for &amp;gt;80 years old), female gender (HR = 1.50), race/ethnicity (HR = 1.34 for Hispanic and 1.21 for Black), stage (HR = 2.26 for distant stage), comorbidity (HR = 2.18 for &amp;gt;1), and radiation (HR = 1.21). When compared to the non-cancer cohort, having a cancer diagnosis (HR = 1.07) and comorbidity (HR = 2.09 for &amp;gt;1) were associated with developing disability. Conclusions: Colorectal diagnosis is an independent risk for disability status. Beyond well-known risk factors “age and mortality” subsets of survivors (Hispanic and Black survivors and those with comorbidity) are found to be at higher risk for developing disability. This warrants further investigation and may indicate targeted intervention to prevent future disability.

Factors associated with subcentimeter pulmonary nodule outcomes followed with computed tomography imaging in oncology patients

IntroductionTechnological advancements in computed tomography (CT) have enabled the frequent detection of small pulmonary nodules (PNs), especially in patients with an oncologic history. It is important the malignant versus benign etiology of PNs be determined. The aim of the present study was to evaluate the behavior and clinical/radiological characteristics of subcentimeter PNs detected by CT in oncologic patients. MethodsAn observational, longitudinal, retrospective and single-center study was conducted with a sample of 100 patients with a diagnosis of a primary malignant solid tumor outside of the lungs who developed indeterminate subcentimeter PNs (n = 251) detected on consecutive thoracic CT scans from 2015 to 2017. Follow-up CTs for each patients were examined in each of three periods (0–3 months, 3–6 months, and 6 months to 1 year). ResultsIn our study sample, 28 patients (28 %) showed one or more signs suspicious of pulmonary metastasis, including ≥50 % PN growth, nodule growth followed by size reduction in patients undergoing chemotherapy, and the appearance of multiple nodules. The majority (56 %) of the PNs were detected during the 3–6-month follow-up CT scan. PNs with irregular, lobuled, or spiculated margins exhibited faster growth than PNs with regular, smooth margins. Malignancy of PNs was found to be significantly associated with being male, a primary colorectal cancer diagnosis, and advanced stage disease. ConclusionOur findings reinforce the necessity of an individualized CT follow-up strategy for patients with an oncologic history, as well as the importance of early nodule screening, with the inter-scan interval being dependent on the primary neoplasm.

96P - Incidence, characteristics and prognosis in colorectal cancer with CNS metastases

BackgroundBrain metastases (BM) due to colorectal cancer (CRC) are an infrequent event. Previous research suggests that patients with pulmonary metastases, rectal primaries and KRAS mutations are at an increased risk of BM. Despite multidisciplinary treatment, survival following BM remains poor. We aimed to analyse the incidence, genomic profiling, treatment administered and survival in patients with BM from CRC within our cancer service. MethodsA retrospective analysis of 1346 CRC patients at two comprehensive cancer centres in Western Sydney identified 52 patients with BM. Data was subsequently collected on patient demographics, tumour and treatment characteristics. KRAS and BRAF mutation status from primary colorectal tumour specimens and surgical resection of BM was assessed. Survival data was analysed by the Kaplan-Meier method. ResultsThe incidence of BM in our cohort was 3.9%. The mean age of patients was 66 (35-82) with 48% female and 52% male in the BM group compared to 36% female and 64% male in the non-BM group. 33% of patients were wildtype (WT), 62% had a RAS mutation and 5% were BRAF mutant. The median time between diagnosis of primary CRC and development of BM did not differ between RAS, RAF and WT (37, 50 and 43 months). 70% of WT patients presented with one BM compared to 45% of KRAS mutated patients although this was not statistically significant (p = 0.13). 38% of patients had surgery while 81% had radiotherapy (56% WBRT, 44% SRS) to treat their BM. The median PFS across all groups was 3.2 months and median OS was 3.9 months. Median PFS was significantly longer in patients who received surgery, chemotherapy and radiotherapy following their diagnosis of BM (12.3 months) versus surgery alone (1 month) or surgery and radiotherapy (4.4 months) (p = 0.022). Mutational status or number of BM did not impact on PFS or OS. Patients with synchronous liver metastases had a significantly shorter median OS of 3 months versus 13 months in those without liver metastases (p = 0.008). ConclusionsBrain metastases remains an infrequent event in patients with metastatic colorectal cancer. KRAS and BRAF mutations do not appear to have any effect on prognosis or response to treatment in CRC patients with BM. Survival of CRC patients following BM is poor and novel approaches are needed. Legal entity responsible for the studyThe authors. FundingWestern Sydney Local Health District. DisclosureK.Y.M. Wong: Advisory / Consultancy: Baxalta; Speaker Bureau / Expert testimony: Sirtex; Travel / ccommodation / Expenses: MSD Oncology. All other authors have declared no conflicts of interest.

Stereotactic Body Radiotherapy for Lung Metastases from Colorectal Cancer: A Single Institution Experience

Aim: Stereotactic body radiotherapy (SBRT) has been used as an alternative to surgical intervention to treat primary malignanices of the lung as well as lesions from other primaries. In this study, we evaluate the safety and efficacy of SBRT in treating lung metastases from colorectal cancer (CRC). Materials &amp; methods: We reviewed 22 patients that underwent lung SBRT for metastases from CRC. Almost all patients received chemotherapy before and after undergoing SBRT. Outcomes that were analyzed included overall survival, distant failure and progression-free survival, as well as the effects of biologically effective dose (BED) and KRAS status on local control. Results: Seven females and 15 males underwent SBRT to lung metastases from CRC. The median Eastern Cooperative Oncology Group status was one (0–2). The median dose was 48 Gy (40–54 Gy) in 5 fx (4–8 fx) and the median number of nodules treated with SBRT was one (1–3). Median follow-up was 28.5 months from SBRT and 79 months (9–145) from primary diagnosis. Local control at 1 and 3 years was 75 and 58%, respectively. There was a trend toward improved local control with increasing biologically effective dose (BED10 &gt; 100; p = 0.07). Cancers that were positive for the KRAS mutation had increased local control at 12 months, 100 versus 75% (p = 0.0199). Median OS from the primary diagnosis of CRC and from SBRT was 79 and 31 months, respectively. There were no predictors for OS. There were no episodes of acute or late grade 3 or higher toxicity. Conclusion: The results of this study add to the growing body of literature to support SBRT for lung metastases, specifically those patients with limited lung metastases from CRC. The choice of radiation dose remains important, even in metastatic disease, as highlighted by the trend toward improved local control with increasing BED10.

Colorectal cancer in South Africa: An assessment of disease presentation, treatment pathways and 5-year survival.

Colorectal cancer (CRC) is the fourth most common cancer in South Africa (SA), and the sixth most lethal. Approximately 25% of patients will have synchronous metastatic disease at the time of their primary CRC diagnosis. Although chemotherapy is used in most stages of the disease, surgical resection of the primary tumour and metastases remains the most successful treatment modality to achieve cure or prolong survival. To date, no data on CRC presentation and management have been published in SA. To determine CRC presentation, general management patterns and overall survival in the SA private healthcare sector. A retrospective review of a private healthcare funder's database from 1 January 2008 to 31 December 2015. International Statistical Classification of Diseases and Related Health Problems (10th revision) (ICD-10) diagnosis codes were used to identify colorectal cancer and liver and/or pulmonary metastatic disease. Procedure codes assigned to hospital admissions were used to identify type of surgical treatment. Chemotherapy was identified by the World Health Organization Anatomical Therapeutic Chemical Classification System of medicines. Treatment patterns were determined and 5-year survival rates for these were calculated. Survival was estimated using the Kaplan-Meier method, and Cox proportional hazards regression was used for between-group comparisons of survival. Data analysis was carried out using SAS version 9.4 for Windows. A total of 3 412 patients were included in the study, 2 267 with CRC only and 1 145 with liver (LM) or pulmonary metastases (PM). The mean age was 64.1 years (range 21 - 97), and 54.6% were male; these did not differ statistically between the study groups. Twenty percent of patients with LM or PM underwent surgical resection of their metastases. Five-year survival rates following surgical resection of all disease for CRC only, CRCLM, CRCPM and CRCLMPM were 71.7%, 57.3%, 31.5% and 26.0%, respectively. SA CRC patients treated in the private healthcare sector have similar disease presentation to that in published international series, with similar outcomes following various treatment pathways; however, it seems that fewer resections of metastases are undertaken compared with international trends.

Colorectal cancer in South Africa: An assessment of disease presentation, treatment pathways and 5-year survival

Background. Colorectal cancer (CRC) is the fourth most common cancer in South Africa (SA), and the sixth most lethal. Approximately 25% of patients will have synchronous metastatic disease at the time of their primary CRC diagnosis. Although chemotherapy is used in most stages of the disease, surgical resection of the primary tumour and metastases remains the most successful treatment modality to achieve cure or prolong survival. To date, no data on CRC presentation and management have been published in SA.Objectives. To determine CRC presentation, general management patterns and overall survival in the SA private healthcare sector.Methods. A retrospective review of a private healthcare funder’s database from 1 January 2008 to 31 December 2015. International Statistical Classification of Diseases and Related Health Problems (10th revision) (ICD-10) diagnosis codes were used to identify colorectal cancer and liver and/or pulmonary metastatic disease. Procedure codes assigned to hospital admissions were used to identify type of surgical treatment. Chemotherapy was identified by the World Health Organization Anatomical Therapeutic Chemical Classification System of medicines. Treatment patterns were determined and 5-year survival rates for these were calculated. Survival was estimated using the Kaplan-Meier method, and Cox proportional hazards regression was used for between-group comparisons of survival. Data analysis was carried out using SAS version 9.4 for Windows.Results. A total of 3 412 patients were included in the study, 2 267 with CRC only and 1 145 with liver (LM) or pulmonary metastases (PM). The mean age was 64.1 years (range 21 - 97), and 54.6% were male; these did not differ statistically between the study groups. Twenty percent of patients with LM or PM underwent surgical resection of their metastases. Five-year survival rates following surgical resection of all disease for CRC only, CRCLM, CRCPM and CRCLMPM were 71.7%, 57.3%, 31.5% and 26.0%, respectively.Conclusions. SA CRC patients treated in the private healthcare sector have similar disease presentation to that in published international series, with similar outcomes following various treatment pathways; however, it seems that fewer resections of metastases are undertaken compared with international trends.

Use of an ACE inhibitor or angiotensin receptor blocker is a major risk factor for dehydration requiring readmission in the setting of a new ileostomy.

Diverting ileostomies help prevent major complications related to anastomoses after colorectal resection but can cause metabolic derangement and hypovolemia, leading to readmission. This paper aims to determine whether angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) use increased the risk of readmission, or readmission specifically for dehydration after new ileostomy creation. Retrospective analysis of patients undergoing diverting ileostomy at a tertiary-care hospital, 2009-2015. Primary outcome was 60-day readmission for dehydration; secondary outcomes included 60-day readmission for any cause, or for infection obstruction. Ninety-nine patients underwent diverting ileostomy creation, 59% with a primary diagnosis of colorectal cancer. The 60-day readmission rate was 36% (n = 36). Of readmitted patients, 39% (n = 14) were admitted for dehydration. Other readmission reasons were infection (33%) and obstruction (3%). The majority (64%, n = 9) of patients readmitted for dehydration were taking either an ACEi or an ARB. Compared to patients not readmitted for dehydration, those who were readmitted for dehydration were more likely to be on an ACEi or an ARB (11/85, 13% vs. 9/14, 64%). After controlling for covariates, ACEi or ARB use was significantly associated with risk of readmission (p < 0.0001, odds ratio = 13.56, 95% confidence interval 3.54-51.92,). No other diuretic agent was statistically associated with readmission for dehydration. ACEi and ARB use is a significant risk factor for readmission for dehydration following diverting ileostomy creation. Consideration should be given to withholding these medications after ileostomy creation to reduce this risk.

Brain metastasis from colorectal cancer: a single center experience.

PurposeThe detection rate of brain metastasis (BM) from colorectal cancer (CRC) is increasing. This study was designed to analyze the clinical features of BM and prognosis according to the therapeutic modalities.MethodsA total of 19 cases were collected in this study between November 2008 and December 2015. We reviewed the patients' demographic data and the clinical features of BM retrospectively and investigated their prognostic significance.ResultsNineteen patients included 8 male and 11 female patients. The median age at diagnosis of BM was 62.4 years (range, 32–83 years). The median interval between diagnosis of CRC and BM was 39 months (range, 0–98 months). Eighteen patients (94.7%) had extracranial metastasis at the diagnosis of BM. Lung was the most common site of extracranial metastasis in 14 patients (73.7%). Synchronous BMs were found at the diagnosis of primary CRC in 2 patients (10.5%). The location of primary CRC was the colon in 6 patients (31.6%) and the rectum in 13 patients (68.4%). At the diagnosis of BM, 10 patients (52.6%) had a solitary BM. The common neurologic symptoms were headache in 8 cases (42.1%) and ataxia in 6 cases (31.6%). The median survival after the diagnosis of BM was 3 months (range, 1–10 months). The patients who underwent surgery plus stereotactic radiosurgery (SRS) had an improved survival (range, 3–10 months) than the other patients (range, 1–6 months) (P = 0.016).ConclusionIn patients with BM from CRC, surgical resection plus SRS might improve survival.

Prevalence and mortality of colorectal cancer with iron deficiency anemia in the South.

e15141 Background: The Centers for Disease Control and Prevention has published data on incidence rates of colorectal cancer (CRC) referenced from the U.S. Cancer Statistics Working Group. Using data on admissions from the National Inpatient Sample (NIS) from 1999-2014. Iron deficiency anemia (IDA) is a commonly encountered comorbidity of CRC, particularly in late stage disease and is associated with higher rates of complications. Methods: Adult admissions with a primary diagnosis of CRC and secondary diagnosis of IDA were extracted from the NIS database using ICD-9 codes from 1999-2014 (N = 5,130, weighted N = 25,594). The sample was weighted to approximate the full inpatient population of the U.S. to analyze differences in regional distribution (Northeast, Midwest, South, and West) we assumed a normal distribution of 25% per region and then performed a chi squared analysis. Results: There were more cases of CRC with IDA in the South (38.32%) compared to the Midwest (22.76%), West (20.45%) and Northeast (18.46%) (p = 0.001). In addition, there were higher rates of mortality from CRC with IDA in the South (29.32%) compared to the Midwest (22.87%), West (21.43%) and Northeast (16.37%) (p &lt; 0.0001). Conclusions: Our data demonstrates a correspondence between the prevalence of IDA associated CRC with a greater prevalence and increased risk of mortality in the South relative to other regions in the U.S.Regional differences in prevalence also corresponded to regional differences in mortality. Future research should investigate the factors that explain these regional disparities.