Mucinous Histology Research Articles

PD-L1 Expression Is Associated with Deficient Mismatch Repair and Poor Prognosis in Middle Eastern Colorectal Cancers.

Several clinical trials are investigating the use of immune-targeted therapy with Programmed death ligand-1 (PD-L1) inhibitors for colorectal cancer (CRC), with promising results for patients with mismatch repair (MMR) deficiency or metastatic CRC. However, the prognostic significance of PD-L1 expression in CRC is controversial and such data are lacking in CRC from Middle Eastern ethnicity. We carried out this large retrospective study to investigate the prognostic and clinico-pathological impact of PD-L1 expression in Middle Eastern CRC using immunohistochemistry. A total of 1148 CRC were analyzed for PD-L1 expression. High PD-L1 expression was noted in 37.3% (428/1148) cases and was correlated with aggressive clinico-pathological features such as high malignancy grade (p < 0.0001), larger tumor size (p = 0.0007) and mucinous histology (p = 0.0005). Interestingly, PD-L1 expression was significantly higher in patients exhibiting MMR deficiency (p = 0.0169) and BRAF mutation (p = 0.0008). Furthermore, the expression of PD-L1 was found to be an independent marker for overall survival (HR = 1.45; 95% CI = 1.06–1.99; p = 0.0200). In conclusion, the results of this study indicate that PD-L1 expression could be a valid biomarker for poor prognosis in Middle Eastern CRC patients. This information can help in decision-making for anti-PD-L1 therapy in Middle Eastern CRC, especially for patients with MMR deficient tumors.

Mucinous Adenocarcinoma of the Appendix With Histologic Response to Neoadjuvant Chemotherapy: Review of Histologic and Clinical Spectrum of Epithelial Neoplastic Mucinous Lesions of the Appendix.

Appendiceal mucinous neoplasms are a rare and heterogeneous group of diseases with challenging clinical management decisions. They account for less than 1% of all cancers but their incidence is on the rise. Treatment is based on their stage and histology. Appendiceal neoplasms frequently metastasize inside the abdomen; this leads to tumor cell growth in the abdominal cavity, known as peritoneal carcinomatosis, and buildup of mucinous material, known as pseudomyxoma peritonei. While low-grade, early-stage tumors can be effectively treated with limited surgical resection, patients with low-grade, advanced-stage disease require peritoneal debulking and hyperthermic intraperitoneal chemotherapy. Therapeutic options for high-grade, advanced-stage mucinous tumors of the appendix have not been well established. Debulking surgery with hyperthermic intraperitoneal chemotherapy preceded and/or followed by systemic chemotherapy has been utilized based on some prospective but not randomized data. We present a case of mucinous adenocarcinoma of the appendix treated with neoadjuvant chemotherapy followed by cytoreductive surgery/hyperthermic intraperitoneal chemotherapy and adjuvant chemotherapy. Preoperative chemotherapy provided a favorable histologic response by converting initial mucinous appendiceal adenocarcinoma histology to a high-grade mucinous appendiceal neoplasm.

Metachronous peritoneal metastases following curative resection for colon cancer: Understanding risk factors and patterns of recurrence.

A subset of metachronous colon cancer recurrence manifests as peritoneal metastases (PM). Risk factors for metachronous PM recurrence are not well-defined in patients with stage II or III colon cancers after curative resection and standard adjuvant treatments. Population data from the California Cancer Registry for patients with Stage II or III colon cancer were collected between 2004 and 2012. Multivariate analysis was used to identify factors associated with metachronous PM. Of the 2077 patients with stage II or III colon cancer, female patients (odds ratio [OR] = 1.84, p = 0.02), T4 primary tumor (OR = 2.36, p = 0.02), mucinous (OR = 3.97, p < 0.01) or signet-ring histology (OR = 6.01, p = 0.01), and right-sided cancer (OR = 2.2, p < 0.01) were found with increased risk of metachronous isolated PM recurrence after curative resection. Median survival after diagnosis for patients without PM recurrence was 22 months, compared with 12 months for PM recurrence (p < 0.001). PM recurrence groups have a worse overall survival than patients with recurrent disease in other sites. A better understanding of the tumor biology and molecular characteristics of colon cancers likely to recur as PM is needed to explain behavior and identify potential targeted therapy.

Increase in the incidence of synchronous and metachronous peritoneal metastases in patients with colorectal cancer: A nationwide study

Introduction– To investigate the incidence of, factors associated with, and differences between synchronous and metachronous colorectal peritoneal metastases (CPM) in a population-based cohort. Methods– Data from the Netherlands Cancer Registry were used. All patients diagnosed with colorectal cancer (CRC) between 1 January and June 30, 2015 were evaluated for synchronous or metachronous CPM (diagnosis ≤90 or >90 days after surgery for primary CRC), and survival in 2019 (median follow-up 38.4 months). Results– Of 7233 included patients, 409 (5.7%) were diagnosed with synchronous CPM. Factors associated with synchronous CPM were mucinous (OR 2.72 [1.90–3.90]) or signet ring cell (SRC) histology (OR 6.58 [3.66–11.81]), T4 (OR 4.82 [3.68–6.32]), N1 (OR 1.66 [1.20–2.30]), or N2 stage (OR 3.27 [2.36–4.52]), and synchronous systemic metastases (SM) (OR 3.13 [2.37–4.14]). After surgery for primary CRC, 326 patients developed metachronous CPM after a median time of 14.7 months (3-year cumulative incidence: 5.5%). Factors associated with metachronous CPM were younger age (HR 1.63 [1.10–2.42]), mucinous (HR 1.84 [1.20–2.82]) or SRC histology (HR 2.43 [1.11–5.32]), T4 (HR 2.77 [2.07–3.70]), N1 (HR 2.90 [2.18–3.85]), N2 (HR 3.19 [2.26–4.50]), and synchronous SM (HR 1.95 [1.43–2.66]). Conclusion– This population-based study found the highest incidence of CPM currently reported in literature and a strong association between the presence of synchronous SM and both synchronous and metachronous CPM. These findings may contribute to a tailored approach in the follow-up after primary CRC surgery and guide future clinical trials investigating new strategies regarding risk-reduction or early detection of metachronous CPM.

Toxicity and Dosimetric Analysis of Early Breast Cancer (EBC) Patients Treated with Ultra-Hypofractionated Weekly Radiotherapy (RT) and Simultaneous Integrated Tumor Bed Boost

EBC patients with advanced age, severe comorbidities/ logistic issues precluding daily treatment were offered ultra-hypofractionated once-weekly RT. For those women requiring additional tumor bed (TB) boost, a simultaneous integrated boost (SIB) was delivered to further reduce the number of hospital visits. We report feasibility and safety of this regimen in EBC patients. Thirty-seven patients of early breast cancer (T1N0: n = 17; T2N0: n = 20) treated from Dec 2018 -Feb 2020 at our institute with breast conservation were included in this study. They received 28.5Gy in 5 weekly fractions to entire breast and a SIB to the TB of 31.5-33Gy using VMAT technique along with image guidance in each fraction. Vacuum bag immobilization and volumetric image guidance with every fraction ensured accurate treatment delivery. The median age was 53 years (IQR: 50 - 61 years) where 19 patients (51%) had left breast cancer. Twenty-one patients (56.7%) had received adjuvant chemotherapy and 28 (75.7%) received concurrent hormonal therapy with RT. TB boost was recommended in view of grade III disease (n = 27), close/involved margins (n = 4), mucinous histology (n = 2) and young age (n = 4). Seven patients (19%) received a SIB doses of 32.5Gy and 27 (73%) received 33Gy. Dosimetric details are shown in table 1. At RT completion out of 30 patients 6, 23 and 1 patient showed RTOG Grade 0, I and II skin reaction respectively. The grade II skin reaction was seen in the axillary fold region within 4 fractions and was treated with the 5th fraction after replanning to underdose the area with skin fold. Once weekly whole breast RT with SIB to TB up to 33Gy in EBC appears to be a safe and feasible. Late toxicity of this regimen needs to be prospectively evaluated.Abstract 2126; TableDosimetric parametersParametersMean ValuesStandard DeviationInter-quartile rangePTV BreastVolume in cc898314.6650 – 1107V 95%96.9%1.5495.8- 98.4%PTV Tumor bedVolume in cc1105870.9 – 128.3V95%98.3%1.7997.3-99.5%Ipsilateral LungMean5.7Gy1.344.9- 6.3GyV5Gy35.7%10.1728.95- 42.1%V20Gy4.7%2.62.7-6.2 %Contralateral LungMean2.1Gy0.751.6- 2.5GyV5Gy5.4%5.10.99- 8.09%HeartMeanLeft -3.09Gy0.812.5-3.6GyRight-2.67Gy1.41.42-3.15GyV5GyLeft-15.3%9.069.4-18.4%Right-12.3%16.71.89-17.65%Left Anterior Descending ArteryMax dose (0.03cc)Left 11.1Gy1.999.3-12.8GyRight 3.8Gy1.492.5-5.1GyBrachial plexusMax dose9.29Gy7.361.6-15.4GyContralateral BreastMean2.4Gy0.811.6- 3.06GyConformity index tumor bedMedian1.080.251.03-1.12 Open table in a new tab

Does the efficacy of regorafenib differ in chemotherapy refractory metastatic colorectal cancer patients who had mucinous pathology compared to those who had non-mucinous pathology?

Purpose: To investigate the importance of mucinous histopathology on the assessment of tumor response in patients with metastatic colorectal cancer (mCRC) receiving regorafenib. Materials and method: All patients diagnosed with histologically confirmed mCRC in 2 oncology centers between 2013 and 2018 were retrospectively analyzed. Among 678 patients diagnosed with mCRC, 103 patients were treated with regorafenib. Ninety-four of these patients who had used at least 2 cycles of regorafenib and evaluable for treatment response were included in the analysis. Histopathologically, 18 patients with mucinous adenocarcinoma and 76 patients with nonmucinous adenocarcinoma were compared in terms of response rate and survival durations. Results: Median follow-up duration of 6 months, median age of the patients was 61 (34-77) years. While 19.1% of the patients had mucinous histology, 80.9% had nonmucinous histology. The overall response rate was significantly lower in the mucinous subgroup than the nonmucinous subgroup (5.6% vs 43.4%, respectively, P = 0.003). Similarly, both progression-free survival (3.0 vs 4.0 months, respectively, P = 0.011) and overall survival duration were shorter in the mucinous subgroup (3.0 vs 7.0 months, P = 0.016, respectively) compared with the nonmucinous subgroup. Conclusion: The histological subgroup may predict tumor response in mCRC patients receiving regorafenib. Its efficacy on nonmucinous histology had significantly more favorable than mucinous subtype.

Epidemiology and Molecular-Pathologic Characteristics of CpG Island Methylator Phenotype (CIMP) in Colorectal Cancer

BackgroundCpG island methylator phenotype (CIMP) forms a distinct epigenetic phenotype in colorectal cancer (CRC). Though associated with distinct clinicopathologic characteristics, limited evidence exists of the association of CIMP with patient’s reported lifestyle factors and tumor molecular characteristics. We assessed the associations of these characteristics in a pooled analysis of CRC patients. Patients and MethodsWe pooled data from 3 CRC patient cohorts: Assessment of Targeted Therapies Against Colorectal Cancer (ATTACC), biomarker-based protocol (Integromics), and The Cancer Genome Atlas (TCGA). CIMP was measured using the classical 6-gene methylated-in-tumor (MINT) marker panel (MINT1, MINT2, MINT31, p14, p16, and MLH1) in ATTACC and genome-wide human methylation arrays in Integromics and TCGA, respectively. CIMP-High (CIMP-H) was defined as ≥ 3 of 6 methylated markers in ATTACC. In TCGA and Integromics, CIMP-H group was defined on the basis of clusters of methylation profiles and high levels of methylation in tumor samples. Baseline comparisons of characteristics across CIMP groups (CIMP-H vs. CIMP-0) were performed by Student t test or chi-square test for continuous or categorical variables, respectively. Further logistic regression analyses were performed to compute the odds ratio (OR) of these associations. ResultsPooled prevalence of CIMP-H was 22% across 3 data sets. CIMP-H CRC tumors were associated with older age at diagnosis (OR, 1.02; 95% confidence interval [CI], 1.01, 1.03), microsatellite instability–high (MSI-H) status (OR, 9.15; 95% CI, 4.45, 18.81), BRAF mutation (OR, 7.70; 95% CI, 4.98, 11.87), right-sided tumor location (OR, 2.40; 95% CI, 1.78, 3.22), poor differentiation (OR, 2.94; 95% CI, 1.95, 4.45), and mucinous histology (OR, 2.47; 95% CI, 1.77, 3.47), as reported previously in the literature. CIMP-H tumors were also found to be associated with self-reported history of alcohol consumption (OR, ever vs. never, 1.58; 95% CI, 1.07, 2.34). Pathologically, CIMP-H tumors were associated with the presence of intraepithelial lymphocytes (OR, 3.31; 95% CI, 1.41, 7.80) among patients in the Integromics cohort. ConclusionCIMP-H tumors were associated with history of alcohol consumption and presence of intraepithelial lymphocytes. In addition, we confirmed the previously known association of CIMP with age, MSI-H status, BRAF mutation, sidedness, and mucinous histology. Molecular pathologic epidemiology associations help us explore the underlying association of lifestyle and clinical factors with molecular subsets like CIMP and help guide cancer prevention and treatment strategies.

Impact of young age on platinum response in women with epithelial ovarian cancer: Results of a large single-institution registry

ObjectiveIn young women, EOC is a rare disease with an uncertain genetic and biological substrate. MethodsWe report a long follow-up of EOC patients treated at Gustave Roussy between 1990 and 2009. We matched young patients aged ≤30 years to randomly selected older patients aged ≥40 years according to known prognostic factors (i.e. FIGO stage, histology and surgical residual disease) and the date of diagnosis with a threshold at the year 2000 to balance the treatment procedures. ResultsEOC was diagnosed in 68 patients aged ≤30 years matched with 111 patients aged ≥40 years. Low-grade (LG) (i.e. serous and endometrioid) (52%, n = 35) and mucinous (i.e. 23%, n = 16 infiltrative and 12% n = 8 expansile) tumors are prevalent. High-grade (HG) tumors are rare (7%, n = 5). Early stage diseases (53%, n = 36 FIGO I/II) are predominant. Response to platinum based chemotherapy is observed to be inferior in young patients as compared to matched older patients (ORR, 29 vs 84% p = 0.0002). For HG tumors the PFS is of 0% at 5 and 10 years in younger as compared to 30% in older patients. No difference in PFS (median 4.9 vs 9.8 ms, p = 0.58) and OS (not reached vs 15.3 ms, p = 0.47) is found overall among younger and older patients respectively. The median follow-up was 72 months (range, 11–288 months). No genetic abnormalities were found. ConclusionsYoung EOC patients are most often diagnosed at an early FIGO stage with LG serous or mucinous histology. Tumors are significantly more resistant to platinum-based chemotherapy in younger patients.

Prognostic implications of mucinous histology in stage III colon cancer with the receipt of adjuvant chemotherapy.

There is still a debate about the survival benefit of chemotherapy in stage III mucinous colon cancer, we then conduct a comprehensive assessment of the efficacy of adjuvant chemotherapy in this population. The data used in the current study were extracted from the Surveillance, Epidemiology and End Results (SEER) database. Chi-squared (χ2) test was used to compared patient characteristics according to the histology. The outcome of the survival analysis used in the current study was cancer-specific survival (CSS). Univariable and multivariable analyses were carried out using the Cox proportional hazards regression models to evaluate the prognostic characteristics associated with CSS of colon cancer. And the risks of mortality were presented as hazard ratios (HRs) with 95% confidence intervals (CIs). A total of 68,976 patients diagnosed with stage III colon cancer were included in our analyses, including mucinous adenocarcinoma (MAC, N=6,592) and non-mucinous adenocarcinoma (NMA, N=62,384). In NMA, the receipt of chemotherapy had 46.0% independently decreased risk of colon cancer-specific mortality compared to non-chemotherapy group (HR =0.540, 95% CI: 0.523-0.558, P<0.001). In MAC, the receipt of chemotherapy had 37.7% independently decreased risk of colon cancer-specific mortality compared to non-chemotherapy group (HR =0.623, 95% CI: 0.566-0.685, P<0.001). MAC was associated with worse prognosis and was less responsive to chemotherapy compared with NMA in stage III colon cancer. However, stage III mucinous colon cancer still need to be treated with chemotherapy because of the significant survival benefit and specialized treatment plans for MAC were quite necessary in the future.

A nomogram based on glycomic biomarkers in serum and clinicopathological characteristics for evaluating the risk of peritoneal metastasis in gastric cancer

BackgroundPeritoneal metastasis (PM) in gastric cancer (GC) remains an untreatable disease, and is difficult to diagnose preoperatively. Here, we aim to establish a novel prediction model.MethodsThe clinicopathologic characteristics of a cohort that included 86 non-metastatic GC patients and 43 PMGC patients from Zhongshan Hospital were retrospectively analysed to identify PM associated variables. Additionally, mass spectrometry and glycomic analysis were applied in the same cohort to find glycomic biomarkers in serum for the diagnosis of PM. A nomogram was established based on the associations between potential risk variables and PM.ResultsOverexpression of 4 N-glycans (H6N5L1E1: m/z 2620.93; H5N5F1E2: m/z 2650.98; H6N5E2, m/z 2666.96; H6N5L1E2, m/z 2940.08); weight loss ≥ 5 kg; tumour size ≥ 3 cm; signet ring cell or mucinous adenocarcinoma histology type; poor differentiation; diffuse or mixed Lauren classification; increased CA19-9, CA125, and CA724 levels; decreased lymphocyte count, haemoglobin, albumin, and pre-albumin levels were identified to be associated with PM. A nomogram that integrated with five independent risk factors (weight loss ≥ 5 kg, CA19-9 ≥ 37 U/mL, CA125 ≥ 35 U/mL, lymphocyte count < 2.0 * 10 ~ 9/L, and H5N5F1E2 expression ≥ 0.0017) achieved a good performance for diagnosis (AUC: 0.892, 95% CI 0.829–0.954). When 160 was set as the cut-off threshold value, the proposed nomogram represented a perfectly discriminating power for both sensitivity (0.97) and specificity (0.88).ConclusionsThe nomogram achieved an individualized assessment of the risk of PM in GC patients; thus, the nomogram could be used to assist clinical decision-making before surgery.

Increase of fallopian tube and decrease of ovarian carcinoma: fact or fake?

Accurate disease classification is fundamental for the selection of the treatment approach, prognostication, selection of clinical trials and for research purposes in routine clinical practice. Extrauterine high-grade serous carcinoma (HG-SC) may arise from the ovary, the fallopian tube and rarely from the peritoneal surface epithelium. Regardless of its origin, the vast majority of patients with HG-SC share clinical symptoms, present with advanced stage disease and suffer from a poor prognosis. Recent data suggest that there is an increasing incidence of HG-SC arising from the fallopian tube. Data from the Clinical Cancer Registry of Leipzig of surgically treated non-uterine pelvic carcinomas were analyzed regarding their sites of origin. Depending on the histology, cases were separated into high-grade serous and non-high-grade serous tumors. Based on different approaches in the assessment of the site of origin, three distinct time periods were defined. The frequency of the specific sites of origin was compared to the different time periods and histologic subtypes. The majority of cases (57.9%; 279/482) were high-grade serous carcinomas, 42.1% of the cases presented with endometrioid, clear cell or mucinous histology. Overall, a 1.7-fold decrease of carcinomas with ovarian origin, paralleled by a 10.3-fold increase of tubal carcinomas was noted between 2000 and 2019. Based on the histopathological subtype, there was a 2.1-fold decrease of ovarian and a 7.1-fold increase of tubal carcinomas in patients with HG-SC. In non-high-grade serous tumors, the frequency of the different sites of origin did not change. 83.7% of tumors with non-high-grade serous histology originated from the ovary, whereas 86.8% of the carcinomas with tubal origin were of high-grade serous histology. The present and published data of non-uterine pelvic cancers may suggest an increase of tubal and decrease of ovarian carcinomas. However, there is rising morphologic and molecular evidence that non-uterine HG-SC actually arise from the fallopian tubes via its precursor STIC instead of from the ovary. This evidence has had an impact on the handling and reporting of non-uterine surgical specimens and its definition of the site assessment. In conclusion, the increasing frequency of tubal carcinomas and the associated decrease in ovarian cancer appears to be due to the reclassification of tumors previously classified as ovarian and greater emphasis on examining the resection specimens of non-uterine pelvic carcinomas.

&lt;p&gt;A Novel Mutation in &lt;em&gt;MYH&lt;/em&gt; Gene Associated with Aggressive Colorectal Cancer in a Child: A Case Report and Review of Literature&lt;/p&gt;

Colorectal cancer is a rare pediatric tumor. Pediatric patients with colorectal cancer present with more aggressive tumor biology and at later stages of the disease, higher proportions of signet ring and mucinous histology, and less differentiation. The effective treatment is same as that received by adults. The overall prognosis of pediatric colorectal cancer is generally poor. Genetic mutations have been identified as the cause of inherited cancer risk in some colorectal cancers. Here, we presented a case of a pediatric patient carrying a maternally derived, heterozygous MYH germline mutation (c.934–2A>G,intron), the mutation was not reported in pediatric patients before. Also, the patient carried somatic mutations of proto-oncogene SMAD4 (R361C) and TP53 (Y234H). The patient underwent surgical resection, chemotherapy and targeted therapy, but the prognosis was not good. We also review the literature to summarize clinical features, gene mutations, management, and outcomes of pediatric colorectal cancer patient. Our results suggest that the genetic mutation of MYH together with somatic mutations of proto-oncogene SMAD4 and TP53 may lead to the early onset colorectal cancer of the patient. Although the overall prognosis of pediatric colorectal cancer is generally poor, the pathogenesis may be related to hereditary genetic mutations as was found with the MYH gene mutation in our case. Genetic screening can provide early diagnosis and improve prognosis.

Development of the 'PREDICT' score through a systematic review and meta-analysis of the predictive parameters for locoregional recurrence after total mesorectal excision.

Despite robust management techniques, locoregional recurrence rates of rectal cancer are still significant. Although offering intensive follow-up has been shown to be beneficial in the early detection, it can be resource consuming. Having a robust knowledge of risk factors of locoregional recurrence will help in identification of patients who actually need intensive follow-up programs. This review aimed to identify the factors that can predict locoregional recurrence after Total mesorectal excision (TME). We systematically reviewed PubMed, Scopus and Cochrane for relevant articles with no date restrictions while language was restricted to English. We only included articles that had either provided Hazards ratio (HR)/odds ratio (OR) or provided enough data that allowed calculation of HR/OR specifically for rectal cancer. Articles were deemed eligible if they included patients undergoing (TME). Seventeen studies (18,605 patients) published between 2002 and 2019 were included. A total of 699 patients developed locoregional recurrence at a median time of 25.2months after surgery. There were eight significant predictors evaluated by more than one study; T3-T4 stage, circumferential resection margin, lymphovascular invasion, mucinous histology, N1-N2 stage, positive distal resection margin, Tumor < 5cm from anal verge, and lack of neoadjuvant radiotherapy. A scoring system was developed based on the weight and pooled OR/HR of each predictor. Using predictive factors identified in our review in context of scoring system may help in the early detection of locoregional recurrence after TME. This may help in tailoring the application of intensive follow-up programs.

Mucinous Histology Might Be an Indicator for Enhanced Survival Benefit of Chemotherapy in Stage II Colon Cancer.

Background: It was a difficult question to identify candidates who would benefit most from adjuvant chemotherapy in stage II colon cancer because of the paucity of relevant conclusive clinical trial results. We aimed to assess if mucinous adenocarcinoma (MUA) could be an indicator for the efficacy of adjuvant chemotherapy in stage II colon cancer.Methods:Using SEER*Stat software V.8.3.5, eligible patients were then recruited from the SEER database. A χ2 test was applied to compare the distribution of different categorical variables between nonmucinous adenocarcinoma (NMUA) and MUA groups. We then used the Kaplan–Meier method to analyze overall survival (OS) of different histological types in stage II colon cancer, and the log-rank test was then used to assess the OS differences. The Cox proportional regression risk models were also built in our analyses to eliminate potential crossed bias from other prognostic factors.Results:A total of 50,065 patients diagnosed with stage II colon cancer were recruited from the SEER database from 2004 to 2011; all the patients were divided into two groups, including NMUA (n = 44,785) and MUA (n = 5,280). The Cox analysis of the histological type indicated that the survival difference between MUA and NMUA failed to reach statistical significance in stage II colon cancer (P = 0.360). In NMUA, patients treated with adjuvant chemotherapy were independently associated with 37.2% decreased risk of overall mortality compared with those not [hazard ratio (HR) = 0.628, 95% confidence interval (CI) = 0.601-1.656, P < 0.001]; in MUA, the number increased to 41.5% (HR = 0.585, 95% CI = 0.515-0.665, P < 0.001).Conclusions:Our study showed that the survival difference between MUA and NMUA failed to reach statistical significance in stage II colon cancer. More importantly, our study had provided the first evidence that chemotherapy would offer higher survival improvement in MUA compared with NMUA in stage II colon cancer; mucinous histology might be an indicator for enhanced survival benefit of chemotherapy in stage II colon cancer.

Baseline radiomics features (RF) in metastatic colorectal cancer (mCRC): Correlation with m site and clinical-pathological characteristics.

e15589 Background: R is an emerging field of research based on the extraction of a large amount of F from biomedical images and on computed analysis algorithms of tumour architecture. Few data regarding mCRC are available, in particular no correlation of baseline RF both with m sites and clinical-pathological characteristics was so far investigated. Methods: Baseline chest-abdomen CT scans of mCRC patients (pts) were retrospectively analysed. RF were extracted from Regions of Interest (ROI) delineated on CT scan from each m sites, including primary tumor, when on site. The association of specific F and disease site (liver, lung, nodes, peritoneum and on-site primary tumor) was investigated. Sites similarity was assessed with Principal Component Analysis, an unsupervised learning technique to identify patterns and clusters. Then RFs were tested individually for correlation with clinical-pathological covariates of interest (gender, CEA level, synchronous disease, RAS/BRAF status, mucinous histology, grading, number of m site, primary tumor site). Wilcoxon-Mann-Whitney test was used for this purpose (significance level set at 0.05). Results: After RF extraction from the different ROIs, the dataset was composed of 433 observations of 236 variables. Observations referred to the number (N) of pts = 89 and the N of ROIs = 18. RF classes were divided in statistical F (grey-level histogram) (N of F = 10); morphological F (N = 14); texture F GLCM (grey level co-occurrence matrix) (N = 100); texture F GLRLM (grey level run length matrix) (N = 66); texture F GLSZM (grey level size zone matrix) (N = 32). Regarding the association of RF with m sites, an homogenous distribution with liver, nodes, peritoneum and primary tumor was detected, while lung metastases showed a different pattern for all the RF classes. A significant correlation of specific RF with clinical-pathologic characteristics was shown, in particular with gender, CEA level, synchronous disease, mucinous histology, RAS/BRAF status. Conclusions: Despite its retrospective nature and the limited number of pts, this is the first experience demonstrating I) a different pattern of RF for lung m versus an homogeneous RF distribution for the other m sites; and II) a significant association of specific RF with few clinical-pathologic characteristics. Our results, if confirmed in a prospective validation set, may represent an hypothesis generator regarding the different behaviour of lung metastases and a possible R signature able to identify different prognostic subgroups of pts.

Factors affecting recurrence rates in women with borderline ovarian tumors.

e18055 Background: Borderline or low malignant potential tumors of the ovary (BOTs) make up approximately 15-20% of all ovarian neoplasms. These tumors are considered indolent and usually confer an excellent overall survival in women who are treated utilizing a conservative surgical approach. However, recurrence rates can approach 30%. The aim of this study was to compare the type and mode of surgery and its impact on outcomes in patients with BOTs. Methods: An Institutional Review Board approved, retrospective cohort study identified all patients at Long Island Jewish Medical Center, North Shore University Hospital and USC Medical Center with BOTs who underwent surgery between January 2008 and May 2018. Demographics and outcome measures were obtained from the medical records. Prognostic factors for disease recurrence were studied including histological subtypes type of surgical procedure, including minimally invasive or open ovarian cystectomy and oophorectomy. Results: 260 patients were identified. 226 of these women (88%) had stage I disease at the time of diagnosis. There were 26 recurrences noted in the cohort, a recurrence rate of 10 percent. The median age was 50 years old (range 16-86). 145 patients (56%) underwent minimally invasive surgical procedures compared to 115 (44%) who had open laparotomy. 30 (12%) of the women underwent an ovarian cystectomy and 230 (88%) had an oophorectomy. The median time to disease recurrence was 25 months (range 4-94 months). There was significant difference in the recurrence free survival between the patients who had minimally invasive procedures and those who had open laparotomy (hazard ratio (HR) 2.69, 95% confidence interval (CI) 1.11-6.52). There was also significant difference in Recurrence Free Survival (RFS) and in those who underwent ovarian cystectomy and oophorectomy (HR 7.32, 95%CI 3.34-16.06). No difference in recurrence rates were noted between those with serous and mucinous histology. Conclusions: In this cohort of women with BOTs, the risk of recurrence was associated with minimally invasive surgery versus open laparotomy as well as ovarian cystectomy compared with oophorectomy. Conservative surgery for BOTs in young patients plays an important role for fertility preservation in these young women and can be curative. This study allows us to present additional information to address surgical approach and risk for disease recurrence in young women having fertility sparing and conservative surgery for BOTs.

The role of primary tumor (PT) site as prognostic factor after resection of colorectal (CRC) liver metastases (LM): A mono-institutional cohort study.

4081 Background: Radical resection of LM is the only chance of cure for liver-only mCRC pts. Besides the evaluation of technical resectability, several factors must be taken into account for the evaluation of recurrence risk. Among them we should consider the Fong Risk Score and its modified version, including RAS/BRAF status (Brudvik’s score). Tumor sidedness is an important prognostic factor in CRC. The impact of PT site on the outcome of LM resection is still debated. Hence, we retrospectively analysed mCRC pts, underwent to radical LM resection at our Institution, investigating the impact of PT site on DFS and OS. Methods: Liver-only mCRC pts underwent to radical LM resection were included. The association of PT site with DFS and OS was evaluated. The following variables were collected: gender; age (≥ vs &lt; 75 years ); ECOG PS; CEA baseline level; PT site; RAS and BRAF status; mucinous histology; grading (G1-2 vs G3); RECIST response during preoperative treatment; resected PT; synchronous vs metachronous; number of LM; bilobar vs unilobar LM; LM diameter ≥ 5 cm; R0 vs R1 resection. Univariate and multivariate analyses for DFS and OS were performed. Results: A total of 463 liver-only mCRC pts underwent to radical LM resection were included. Seventy (15%) pts had a right-sided (r-s) tumor and 393 (85%) pts a left-sided (l-s) tumor. R-s CRC pts more often had RAS/BRAF mutations in comparison to l-s tumors (76% vs 37%; p &lt; 0.0001). Median DFS and OS was 13.1 and 41.6 months, respectively, in r-s CRC vs 16.0 (p = 0.65) and 62.2 months (p = 0.033), respectively, in l-s tumors. At the multivariate analysis no significant association with survival parameters was shown for tumor sidedness. At the multivariate analysis, R0 resection was independently associated both with better DFS and OS; RAS/BRAF wt CRC and resected PT were significantly associated with improved OS. Considering all wt CRC pts (N = 237), 14 (6%) pts had r-s tumor and 223 (94%) l-s tumor. No significant association of tumor sidedness with survival was shown (DFS r = 10.0 vs l = 16.0 months, p = 0.62; OS r = 40.3 vs l = 66.2 months, p = 0.12). Conclusions: Our results showed that a significant smaller proportion of r-s CRC underwent to radical LM resection, indirectly confirming its worse prognosis. Among radically resected pts, r-s CRC was associated to a shorter OS (significant) and DFS (not significant) compared to l-s CRC, but it was not confirmed at the multivariate analysis. We can conclude that right PT site should not be considered as a contraindication for radical LM surgery, when feasible.

KRAS amplification in metastatic colon cancer is associated with a history of inflammatory bowel disease and may confer resistance to anti-EGFR therapy.

Mutations in RAS occur in 30–50% of metastatic colorectal carcinomas (mCRCs) and correlate with resistance to anti-EGFR therapy. Consequently, mCRC biomarker guidelines state RAS mutational testing should be performed when considering EGFR inhibitor treatment. However, a small subset of mCRCs are reported to harbor RAS amplification. In order to elucidate the clinicopathologic features and anti-EGFR treatment response associated with RAS amplification, we retrospectively reviewed a large cohort of mCRC patients that underwent targeted next-generation sequencing and copy number analysis for KRAS, NRAS, HRAS, BRAF and PIK3CA. Molecular testing was performed on 1,286 consecutive mCRC from 1,271 patients as part of routine clinical care, and results were correlated with clinicopathologic findings, mismatch repair (MMR) status and follow-up. RAS amplification was detected in 22 (2%) mCRCs and included: KRAS, NRAS and HRAS for 15, 5 and 2 cases, respectively (6 to 21 gene copies). Patients with a KRAS-amplified mCRC were more likely to report a history of inflammatory bowel disease (p < 0.001). In contrast, mutations in KRAS were associated with older patient age, right-sided colonic origin, low-grade differentiation, mucinous histology and MMR proficiency (p ≤ 0.017). Four patients with a KRAS-amplified mCRC and no concomitant RAS/BRAF/PIK3CA mutations received EGFR inhibitor-based therapy, and none demonstrated a clinicoradiographic response. The therapeutic impact of RAS amplification was further evaluated using a separate, multi-institutional cohort of 23 patients. Eight of 23 patients with KRAS-amplified mCRC received anti-EGFR therapy and all 8 patients exhibited disease progression on treatment. Although the number of KRAS-amplified mCRCs is limited, our data suggests the clinicopathologic features associated with mCRC harboring a KRAS amplification are distinct from those associated with a KRAS mutation. However, both alterations seem to confer EGFR inhibitor resistance and, therefore, RAS testing to include copy number analyses may be of consideration in the treatment of mCRC.

Mucinous Histology, BRCA1/2 Mutations, and Elevated Tumor Mutational Burden in Colorectal Cancer.

Mucinous colorectal carcinomas (MC) constitute 10% of colorectal malignancies. Recently, an increased risk of colorectal cancer has been demonstrated in germline BRCA1/2 mutation carriers. Furthermore, BRCA1/2 germline mutation carriers have exhibited a higher-than-expected frequency of MC tumors. Here, we investigate the relationship between BRCA mutations and mucinous histology in colorectal carcinoma patients, using both an existing cohort of sequenced colorectal tumors and a prospective case-control study comparing MC and conventional adenocarcinoma (AC) patients tested for BRCA mutations. We discovered that MC tumors exhibit a statistically significantly higher incidence of BRCA mutations in addition to a higher average mutation count when compared to AC tumors in the existing cohort. The strongest predictor of the mutation count was mucinous histology, independently of other variables including microsatellite instability. Contrary to our hypothesis, the first association did not recur in the prospective case-control study, likely due to our pathological definition of MC tumors and small sample size. Finally, we observed a higher tumor mutational burden (TMB) in MC tumors compared with AC tumors. We suggest that the association between MC histology, BRCA mutations, and increased TMB may open the door to the utilization of simple tests (such as histopathologic characterization) to detect patients who may benefit from immunotherapy in colorectal cancer.

Are tumour grade and tumour budding equivalent in colorectal cancer? A retrospective analysis of 771 patients

BackgroundTumour grade is traditionally considered in the management of patients with colorectal cancer. However, a large body of literature suggests that a related feature, namely tumour budding, may have a more important clinical impact. The aim of our study is to determine the correlation between tumour grade and tumour budding and their impact on patient outcome. MethodsA retrospective collective of 771 patients with colorectal cancer were included in the study. Clinicopathological information included tumour grade (World Health Organisation 2010; G1, G2 and G3) and tumour budding evaluated as BD1, BD2 and BD3 and representing 0–4 buds, 5–9 buds and 10 or more buds per 0.785 mm2, respectively. ResultsTumour grade and tumour budding were correlated (p < 0.0001, percent concordance: 33.8%). Of the BD1 cases, 18.1% were of G3. Only two BD3 cases were G1. Both high tumour grade and tumour budding were associated with higher pT, lymph node metastasis, distant metastasis and lymphatic and venous vessel invasion (p < 0.01, all), but only tumour grade was additionally associated with right-sided tumour location and mucinous histology. Higher tumour budding led to worse overall (p = 0.0286) and disease-free survival (p = 0.001), but tumour grade did not. Budding was independent of tumour grade in multivariate analysis. DiscussionTumour grade and tumour budding are distinct features, as recognised by their different clinicopathological associations, reflecting different underlying biological processes. Nonetheless, tumour budding seems to outperform tumour grade in terms of predicting disease-free survival.