Low CEA Level Research Articles

Unveiling the mille-feuille sign: a key to diagnosing ovarian carcinosarcoma in addition to ovarian metastasis from colorectal carcinoma on MRI.

To clarify the diagnostic utility and formation of the Mille-feuille sign for ovarian carcinosarcoma (OCS) on MRI, and to evaluate the other MRI findings and serum markers compared to ovarian metastases from colorectal carcinoma (OMCRC). Three blinded radiologists retrospectively reviewed MR images of 12 patients with OCS, 18 with OMCRC, and 40 with primary ovarian carcinoma (POC) identified by the electronic database of radiology reports. The interobserver agreement was analyzed using Fleiss' kappa test. Their MRI characteristics and tumor markers were compared using Fisher's exact test and Mann-Whitney's U test. Receiver operating characteristic curve analyses were used to determine the cutoff points for the ADC value. This study was approved by the institutional ethics committee. Interobserver agreement analysis was moderate or higher for all MRI characteristics. The frequency of Mille-feuille sign was comparable for both OCS and OMCRC groups, and predominantly higher than that of the POC group (p < 0.001, p < 0.001), respectively. Pathologically, the Mille-feuille sign in OCS reflected alternating layers of tumor cells with stroma and necrosis or intraluminal necrotic debris. Compared to OMCRC, intratumoral hemorrhage (p = 0.02), margin irregularity (p = 0.048), unilateral adnexal mass (p = 0.02), and low ADC values (p < 0.01) were more frequently observed and serum CEA levels was significantly lower (p = 0.007) in the OCS group. Under setting of the cutoff value of ADC at 0.871 × 10-3mm2/s, the discriminative ability for OCS showed 66.7% sensitivity, 94.4% specificity, and 81.0% accuracy, respectively. The Mille-feuille sign was seen in both OCS and OMCRC. MR findings of intratumoral hemorrhage, margin irregularity, unilateral adnexal mass, low ADC values, and low serum CEA levels can be useful in differentiating OCS from OMCRC.

Survival benefit and clinical characteristics of patients with metastatic colorectal cancer (mCRC) receiving pulmonary metastasectomy.

59 Background: The role of lung metastasectomy in mCRC remains a topic of particular controversy, being uncertain which patients benefit more from it and whether it leads to better survival outcomes. Our aim was to identify clinical and molecular differences and survival data in a cohort from a tertiary care hospital. Methods: We retrospectively analyzed 115 patients with lung metastases from colorectal cancer (CRC) in a tumor registry from 2015 to 2021, analyzing clinical and molecular characteristics, as well as overall survival (OS) data of patients who received lung metastasectomy versus patients who did not. Results: Among all patients, 36 (31.3%) received pulmonary metastases surgery. Patients undergoing metastases resection had more frequently ECOG 0 (51.4% vs 20.8%, p = 0.0011), resected primary tumor (100% vs 78.5%, p = 0.0026), metachronous metastatic disease (75% vs 46.8%, p = 0.0048) and a single metastatic location (79.4% vs 41%, p = 0.0002). In addition, none of them had BRAF mutation (0% vs 17.1%, p = 0.04); however, no statistically significant differences were found regarding KRAS, NRAS, PI3K, HER2 or presence of microsatellite instability (MSI). Patients who received lung metastasectomy had higher BMI (26.1 vs 24.4, p = 0.037) and lower mean levels of CEA (19.5 vs 142.9, p = 0.007), CA 19.9 (30.6 vs 244.9, p = 0.011) and LDH (159 vs 211.9, p = 0.018). We found an OS benefit in patients undergoing metastatic surgery (median not reached (NR) vs 41.4 months, HR for death 0.27, 95% CI, 0.14 - 0.53, p &lt; 0.000); a multivariate analysis confirmed that this benefit was independent from the characteristics mentioned above. The median progression-free survival (PFS) after metastases resection was 53.3 months. Conclusions: In our study, patients who were more likely to receive lung metastasectomy were those with ECOG 0, resected primary tumor, metachronous disseminated disease, a single metastatic location, native BRAF mutation status and low CEA, CA 19.9 and LDH levels, with a significant OS benefit associated.

Predictive biomarkers for response to immunotherapy in patients with deficient DNA mismatch repair metastatic colorectal cancer.

254 Background: Deficient DNA mismatch repair (MMRD) accounts for approximately 3% of metastatic colorectal cancers (mCRC). Treatment with Immune checkpoint inhibitors (ICI) in this patient population achieve an overall response rate (ORR) of up to 55%. However, to date there are no predictive biomarkers for response. Methods: A retrospective analysis of all MMRD mCRC patients that were treated with either Pembrolizumab, or Ipilimumab and Nivolumab in a large tertiary medical center between 2015-2022. The primary outcome was response to treatment and was assessed at first imaging following treatment initiation. Exposure variables included age, sex, ECOG performance status, metastatic sites (liver, peritoneum, lung, bone and brain) and CEA levels at treatment initiation. CEA below 5 mcg/l was treated as low and above as high CEA levels. Predictive biomarkers were assessed using cox hazard regression and Kaplan Meier analysis. Results: A total of 33 prospective MMRD mCRC patients were included in the study. Of them, 24 (72.7%) responded and 9 (27.3%) did not respond to immunotherapy. Median age was 70 (IQR 66-77) and 64 (IQR 51-75) for responders and non-responders respectively. Site of metastasis was an important predictor for response. Thirteen patients had liver metastasis, of them 6 (46%) responded (HR = 7.16; 95% CI = 1.47-35; p = 0.015). Five patients had single site metastasis in the liver, of them one (20%) responded (HR = 12.7; 95% CI = 2.99-53.8; p &lt; 0.001). Fifteen patients had peritoneal metastasis, of them 13 (87%) responded to treatment (HR = 0.24; 95% CI = 0.05-1.19; p = 0.081). Median CEA at treatment initiation was 2 (IQR 1-4) in responders compared to 32 (IQR 1-70) for non-responders (HR = 5.27; 95% CI = 1.31-21.2; p = 0.019). There was no statistically significant difference between the groups in age, sex and ECOG performance status. Conclusions: Liver metastasis predict poor response to immunotherapy in MMRD mCRC patients while peritoneal metastasis and low CEA level predict response to immunotherapy.

Construction and Evaluation of Nomogram for Hematological Indicators to Predict Pathological Response after Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer

ObjectiveA retrospective study was conducted by developing prediction models to evaluate the association between hematological indexes, their changes during neoadjuvant chemoradiotherapy (NCRT), and tumor pathological response in patients with locally advanced rectal cancer.MethodsThe clinical data of 202 patients who received NCRT and radical surgery in Sichuan Cancer Hospital were retrospectively analyzed. Univariate and logistic multivariate regression analyses were used to identify hematological indexes with predictive significance. The independent risk factors were imported into the R software, and a nomogram prediction model was developed. The bootstrap method and ROC curve were used to evaluate the discriminative degree of the model.ResultsUnivariate analysis demonstrated age, tumor diameter, preoperative T, distance from tumor to the anal verge, CEA before NCRT, preoperative CEA, lymphocyte changes, platelet changes, and pathology of rectal cancer after NCRT were associated. Multivariate analysis demonstrated that age, tumor distance from the anus, preoperative CEA, lymphocyte changes, and platelet changes were independent risk factors. The independent risk factors were imported into the R software to construct a nomogram model. The area under the ROC was 0.76, and the slope of the calibration curve of the nomogram was close to 1.ConclusionA low preoperative CEA level, a young age, a high tumor from the anal verge, the maintenance of circulating lymphocyte level, and a decreased platelet level after NCRT are important factors for favorable outcomes after NCRT. Developing a nomogram prediction model with good discrimination and consistency can provide some guidance for predicting pathological responses after NCRT.

Oncological Outcome of Conversion Surgery After Preoperative Chemotherapy for Metastatic Pancreatic Cancer.

To investigate the outcome of conversion surgery in patients with metastatic pancreatic cancer (mPDAC) and to identify patients who may benefit from this approach. The role of conversion surgery in patients with mPDAC and exceptional response to chemotherapy remains unclear. Patients who underwent surgical exploration for mPDAC following chemotherapy between 2006 and 2019 were included. Data on demographics, oncologic treatment, pathology, and postoperative outcomes were analyzed. Univariate and multivariate survival analyses were performed. Some 173 patients received preoperative chemotherapy and underwent surgical exploration. Ninety-three patients underwent resection of the primary tumor and metastatic sites, 80 patients underwent exploration only. In the resection subgroup, 45 patients had complete pathological response of metastases (ypM0) and 48 patients had residual metastases (ypM1). ypM0 status was associated with lower carcinoembryonic antigen levels and lower ypN stage. Overall survival after resection was 25.5 months in ypM0, 10.7 months in ypM1, and 8.1 months in patients without resection ( P <0.001). Additional adjuvant chemotherapy was significantly associated with prolonged survival in resected patients (29.0 vs 14.8mo, P =0.024) as well as in ypM0 (29.1 vs 19.2mo, P =0.047). Multivariable analysis identified conversion surgery, carbohydrate antigen 19-9 (CA19-9) and time of resection as independent prognostic markers for the entire cohort. CA19-9, ypM0 and adjuvant treatment were independent predictors of survival in the resection subgroup. In patients with mPDAC and ypM0 status after chemotherapy, surgical resection is associated with encouraging survival. mPDAC patients with exceptional response to chemotherapy may be candidates for exploration and for resection in ypM0. Adjuvant chemotherapy may provide an additional survival advantage.

An Eight-CpG-based Methylation Classifier for Preoperative Discriminating Early and Advanced-Late Stage of Colorectal Cancer.

AimTo develop and validate a CpG-based classifier for preoperative discrimination of early and advanced-late stage colorectal cancer (CRC).MethodsWe identified an epigenetic signature based on methylation status of multiple CpG sites (CpGs) from 372 subjects in The Cancer Genome Atlas (TCGA) CRC cohort, and an external cohort (GSE48684) with 64 subjects by LASSO regression algorithm. A classifier derived from the methylation signature was used to establish a multivariable logistic regression model to predict the advanced-late stage of CRC. A nomogram was further developed by incorporating the classifier and some independent clinical risk factors, and its performance was evaluated by discrimination and calibration analysis. The prognostic value of the classifier was determined by survival analysis. Furthermore, the diagnostic performance of several CpGs in the methylation signature was evaluated.ResultsThe eight-CpG-based methylation signature discriminated early stage from advanced-late stage CRC, with a satisfactory AUC of more than 0.700 in both the training and validation sets. This methylation classifier was identified as an independent predictor for CRC staging. The nomogram showed favorable predictive power for preoperative staging, and the C-index reached 0.817 (95% CI: 0.753–0.881) and 0.817 (95% CI: 0.721–0.913) in another training set and validation set respectively, with good calibration. The patients stratified in the high-risk group by the methylation classifier had significantly worse survival outcome than those in the low-risk group. Combination diagnosis utilizing only four of the eight specific CpGs performed well, even in CRC patients with low CEA level or at early stage.ConclusionsOur classifier is a valuable predictive indicator that can supplement established methods for more accurate preoperative staging and also provides prognostic information for CRC patients. Besides, the combination of multiple CpGs has a high value in the diagnosis of CRC.

Prognostic Factors of Survival with Aflibercept and FOLFIRI (fluorouracil, leucovorin, irinotecan) as Second-line Therapy for Patients with Metastatic Colorectal Cancer.

Background: Aflibercept and fluorouracil, leucovorin, irinotecan (FOLFIRI) is commonly used as a second-line treatment for metastatic colorectal cancer (CRC). However, the biomarkers to guide the choice of this regimen from among treatment options remain unclear.Patients and Methods: We performed exploratory analyses to validate potential prognostic factors for patients receiving aflibercept plus FOLFIRI as a second-line systemic treatment for metastatic CRC between January 2015 and July 2019. Patient characteristics, histopathologic data, laboratory and radiologic data, and treatment outcomes were collected and reviewed.Results: Included were 52 patients: 50 (96.2%) received bevacizumab plus fluorouracil, leucovorin, oxaliplatin (FOLFOX) as prior first-line treatment. Among the 52 patients receiving aflibercept and FOLFIRI, four complete responses and 21 partial responses were observed in analyzed patients for an overall response rate of 48.1%. Median progression-free survival (PFS) was 7.0 months and overall survival (OS) was 16.8 months. Response to first-line treatment (median PFS, 8.0 versus 4.2 months), left-side location of primary tumor (7.9 versus 4.9 months), low baseline CEA level (8.0 versus 5.9 months), and no RAS/RAF mutation (9.9 versus 6.4 months) were remained significant prognostic factors for PFS in the multivariate backward stepwise Cox regression model, and the latter three factors were also significantly related to OS.Conclusions: Significant prognostic factors for PFS with aflibercept plus FOLFIRI as second-line therapy were extracted and validated in the multivariate OS model. These findings could provide useful information for selecting patients for aflibercept plus FOLFIRI as second-line therapy.

Survival benefit and toxicity profile of adjuvant icotinib for patients with EGFR mutation-positive non-small cell lung carcinoma: a retrospective study.

BackgroundAdjuvant epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are increasing considered for the tailored management of resectable non-small cell lung cancer (NSCLC). This study aimed to analyze the survival and toxicity profile of patients with EGFR mutation-positive NSCLC treated with adjuvant icotinib.MethodsThis was a single-center retrospective study of patients with EGFR mutation-positive NSCLC who underwent R0 (microscopically margin-negative) resection and received adjuvant icotinib between November 2011 and December 2017. The outcomes included 2-year disease-free survival (DFS) rate, 3-year overall survival (OS) rates, DFS, OS, and adverse events (AEs).ResultsA total of 86 patients receiving adjuvant icotinib were included. Their mean age was 59.7±10.0 years, and 26 (30.2%) patients were male. The 2-year DFS rate was 86.7%, and the 3-year OS rate was 95.3% with adjuvant icotinib. DFS (P=0.044) and OS (P=0.003) are better in stage I/II disease than in stage III disease. There seems no differences in DFS and OS between patients with low or high preoperative CEA levels (cutoff of 5 ng/mL), patients with exon 19 or 21 EGFR mutation or patients with or without smoking history. The most common AEs with adjuvant icotinib were rash (83.7%) and diarrhea (19.8%). One (1.2%) patient-reported grade ≥3 AEs. No treatment-related death occurred.ConclusionsFor patients with EGFR mutation-positive NSCLC, adjuvant icotinib might be associated with a promising survival benefit, with an acceptable toxicity profile.

Identification of clinical features to predict the consistency of mutational profiles obtained from plasma and tissue of advanced non-small cell lung cancer (NSCLC) patients.

e21537 Background: Due to its non-invasiveness and advantage in overcoming tumor heterogeneity, plasma-based genomic profiling is widely used in advanced NSCLC patients for treatment guidance. However, whether the mutational profile derived from ctDNA comprehensively represents that in tumor tissue is the major concern for the application. It has been reported that a variety of factors influence the consistency of mutational profile between plasma and tissue samples. This study explores clinical features which predict the concordance between tissue and plasma samples. Methods: Paired tissue and plasma samples were collected from 79 (stage III and IV) NSCLC patients. Samples were profiled using a 520-cancer-related gene panel. Serum markers such as CEA, CA199, SCC and NSE were collected. Results: All tissue samples except for 1 (98.7%) had mutations detected from this panel. 68 plasma samples (86%) had mutations detected from this panel. The overall concordance of mutation between plasma and tissue samples was 43%; and the concordances for point mutation and copy number variations were 60.2% and 15%, respectively. The concordance for 8 classic lung cancer driver genes and druggable mutations were 77.2% and 34.2%, respectively. Next, we explore the correlation of serum biomarkers and the concordance rate. Univariate analyses revealed that CA19-9 (P &lt; 0.001) and CEA (P = 0.01) were significantly associated with the concordance rate of actionable mutations. Using CEA &gt; 5ng/ml as a cutoff, 43.1% patients having higher CEA level harbored an identical mutation profile between plasma and tissue vs only 20.8% patients with lower CEA level had an identical mutation profile (p = 0.01). Furthermore, 75% patients with CA 19-9 &gt; 39U/ml harbored an identical mutation profile between plasma and tissue vs 22.8% patients with CA19-9 £ 39U/ml (P &lt; 0.001). Combining both CEA and CA19-9 can effectively predict the concordance (p &lt; 0.001); 85.7% of patients with CEA and CA19-9 levels above the cutoff have identical mutation profile and only 34.2% patients with either one or both below the cutoff have identical mutation profile (p &lt; 0.001). Conclusions: We identified the clinical and molecular factors which showed promising value in predicting the consistency of mutational profile between plasma and tissue in NSCLC patients. Plasma samples of patients with high CEA ( &gt; 5ng/ml) and CA19-91 ( &gt; 39U/ml) can comprehensively reflect the mutation profile of tumor samples. Tissue biopsy is not necessary for such patients.

Perioperative Circulating Tumor DNA in Colorectal Liver Metastases: Concordance with Metastatic Tissue and Predictive Value for Tumor Burden and Prognosis.

BackgroundThe surgical resection of colorectal cancer with liver metastases (CLM) has proven to be the most important modality for long-term survival, while effective biomarkers for outcome prediction or postoperative surveillance are still lacking. Currently, circulating biomarkers obtained from a liquid biopsy are widely used to assess the treatment response, disease recurrence and progression. In this study, we analyzed the value of the liquid biopsy, which includes circulating tumor DNA (ctDNA) and cell-free DNA (cfDNA), in patients with CLM.MethodsCapture-based targeted deep sequencing was performed on matched pre-surgery, post-surgery and liver metastatic tissues of 20 CRC patients who underwent the resection of liver metastases between May and September 2017 using a panel consisting of 41 genes. Mutation landscapes obtained from pre-surgery plasma samples and metastatic tissue samples were compared.ResultsCollectively, we identified 47 mutations from 17 pre-surgery plasma samples (85%), and the remaining 3 patients had no mutation detected from the panel. We revealed a high by-variant concordance rate of 82.14% between pre-surgery plasma samples and liver metastatic tissue samples. We further analyzed the correlation between ctDNA, cfDNA, CEA and tumor burden and revealed a positive correlation between ctDNA and tumor burden (R=0.69, p=0.002). As of the date for data cutoff, 8/20 patients experienced relapse. Our study also demonstrated that pre-surgery ctDNA (p<0.001), cfDNA (p=0.001) and CEA (p=0.012) levels had predictive value for relapse. Patients with low pre-surgery ctDNA (p<0.001), cfDNA (p=0.001) or CEA (p=0.012) levels were more likely to experience prolonged progression-free survival.ConclusionOur data demonstrate that the genomic profile obtained from ctDNA is comparable with the genomic profile obtained from metastatic liver tumors. Furthermore, our study also show that pre-surgery ctDNA levels are positively correlated with tumor burden. In addition, pre-surgery ctDNA, cfDNA and CEA levels have predictive value for relapse.

Pancreatic abscess within hepato-gastric ligament: case report of an extremely rare disease

BackgroundPancreatic pseudocyst is a very common benign cystic lesion of the pancreas. It develops in 5–15% of patients with peri-pancreatic fluid collection following acute pancreatitis. Collection usually occurs within the lesser sac of the omentum (near the pancreatic head and body region). But in 20–22% cases, that may be extra-pancreatic like in the mediastinum, pleura, in the peritoneal cavity including the pelvis. The pancreatic pseudocyst typically contains brownish fluid with necrotic tissue sludge which may get infected giving rise to infected pseudocyst or pancreatic abscess. The present case is an unusual condition of a young alcoholic subject who was finally diagnosed as a case of a pancreatic abscess within hepato-gastric ligament and was managed with operative intervention.To the best of the author’s knowledge, it is the first-ever reported case of a pancreatic abscess within the hepato-gastric ligament in the world. Literature was reviewed to explore potential etiopathogenesis and therapeutic strategies of this extremely rare condition.Case presentationA 38 years old gentleman, chronic alcoholic, having a previous history of acute pancreatitis 3 months back, presented with fever (102 degrees Fahrenheit) and a huge [20 cm (horizontal) X 15 cm (vertical)] severely painful swelling in the epigastric region. The swelling was round-shaped, intra-abdominal, fixed to deeper tissue, tense-cystic, poorly trans-illuminant, non-pulsatile and irreducible. Routine blood tests showed leucocytosis (14,500/mm3) with neutrophilia and elevated plasma pancreatic amylase and lipase levels. USG and MDCT scan of the whole abdomen revealed a thick-walled echogenic cystic swelling of size 18 cm × 12 cm in the epigastric region. USG guided aspiration of the cyst revealed mixed purulent brownish fluid. The cyst fluid was negative for mucin stain and contained high amylase level with low CEA level, suggesting infected pancreatic pseudocyst.An open drainage procedure was considered through an upper midline laparotomy. Aspiration of the pus mixed cyst fluid along with tissue debris was done. Through irrigation of the cyst was done with normal saline. The cyst wall was de-roofed leaving a small part adherent to the inferior surface of the left lobe of the liver. Later the cyst fluid culture showed significant growth of Escherichia coli. He was put on IV antibiotics. The patient was discharged in a stable condition after 5 days. The histopathological examination confirmed pancreatic abscess.Six months after the operation, the patient is doing well, remaining asymptomatic and there is no sign of recurrence.ConclusionsDue to extreme rarity, pancreatic abscess formation within hepato-gastric ligament may be a diagnostic dilemma and requires a high index of suspicion. Surgeons should be aware of this rare clinical entity for prompt management of potential morbidity.

Prognostic factors of EGFR-mutated metastatic adenocarcinoma of lung

PurposeThe first-line treatment of metastatic lung adenocarcinoma with epidermal growth factor receptor (EGFR) mutation is tyrosine kinase inhibitor (TKI). This study aimed to evaluate potential factors affecting the progression-free survival under TKI treatment. MethodsForty one patients with EGFR-mutated metastatic lung adenocarcinoma under first-line TKI treatment were retrospectively evaluated. Ten factors potentially influencing the progression-free survival were studied: patients’ age, gender, smoking history, number of comorbidities, performance status, tumor mutation site, maximum of standardized uptake value (SUVmax) of primary tumor in FDG PET/CT, serum CEA level, number of metastatic organs and presence of pleural/pericardial effusion. Mantel-Cox tests and waterfall plots were performed for statistical analyses. ResultsStatistical evaluation demonstrated that primary SUVmax, serum CEA level, gender and smoking history were important prognostic factors, with corresponding p values of 0.001, 0.023, 0.034 and 0.041 respectively in Mantel-Cox analyses. ConclusionLow primary SUVmax, low serum CEA level, female and never smoker were four prognostic factors suggestive of good response to TKI in mutated EGFR metastatic lung adenocarcinoma. SUVmax is probably the most important among the four factors.

Decreased expression of SorCS1 in colorectal cancer: An independent predictor of poor prognosis.

Previously, we identified that sortilin related VPS10 domain containing receptor 1 (SorCS1) was hypermethylated in colorectal cancer (CRC) tissues. Here, we aimed to investigate the association between CRC and SorCS1. DNA methylation was determined by methylation-specific polymerase chain reaction (MSP) or quantitative real-time methylation analysis (MethyLight). Colorectal cancer tissue specimens from 239 patients that had undergone surgical treatment were evaluated using immunohistochemistry (IHC) analysis for the expression of SorCS1 and correlated with clinicopathological variables and prognosis. We found that SorCS1 was hypermethylated in CRC cell lines and 67.5% (27/40) CRC tumor tissues. The loss of SorCS1 mRNA (p<0.001) and protein expression (p=0.033) were highly correlated with promoter methylation. In addition, SorCS1 expression was significantly increased in younger patients (p=0.006), low CEA level (p<0.001) and pT1-2 stage (p=0.005). Survival analysis revealed that decreased expression of SorCS1 was an independent factor for predicting the increased risk of recurrence (p=0.024) and poor overall survival (p=0.006). Subgroup analysis for CEA level, pT and pN classifications showed that SorCS1 retained its stratified significance only in patients with low CEA level, pT3-4 tumors and pN1-2 lymph node status. Our findings suggest that SorCS1 is epigenetically inactivated in a substantial fraction of CRC, and its expression may be a promising prognostic factor in CRC patients.

Abstract 4898: Clinical application of quantitative multiplex mass spectrometry-based proteomics in predicting clinical outcomes in locally advanced rectal cancer

Abstract Background: Neoadjuvant chemoradiotherapy (CRT) using 5-fluorouracil (5-FU) is a standard treatment for locally advanced rectal cancer (LARC) to improve clinical outcomes. The pathologic responses after neoadjuvant CRT is a major prognostic factor, thus identification of good or poor responder in advance is important. This study is to find candidate predictive biomarkers for CRT and prognosis in LARC patients using quantitative mass spectrometry (MS). Materials and methods: 86 patients with stage II/III LARC, received neoadjuvant CRT consisting of 5-FU/leucovorin followed by surgery were included. 14 proteins potentially associated with 5-FU activity or prognosis were evaluated in archived formalin-fixed, paraffin-embedded pre- and post-CRT tumor tissues using MS: DHFR, DPYD, EGFR, hENT1, Her2, MET, OPRT, p16, TK1, TYMP, TYMS, UCK1, UCK2, UPP1. Tumor regression grade (TRG) after CRT was assessed by Dworak criteria: 0, no regression; 1, dominant tumor mass with obvious fibrosis; 2, dominant fibrotic changes with few tumor cells; 3, very few tumor cells; 4, no tumor cells. Results: TGR was 0 in 2 (2.3%), 1 in 30 (34.9%), 2 in 23 (26.7%), 3 in 20 (23.3%), and 4 in 11(12.8%) patients. Major regression (TRG 2/3/4) was associated with high TK1 (P = 0.040), low TYMS (P = 0.037), p16 (P = 0.055), and UPP1 (P = 0.028) levels. Among the pre-CRT parameters, low CEA level (&amp;lt;5ng/mL, P = 0.013), clinical stage II (P&amp;lt;0.001), tumor differentiation (good, P = 0.052), low EGFR level (&amp;lt;200amol/ug, P=0.006), undetectable TYMS level (P = 0.070) were associated with longer recurrence-free survival (RFS). Among the post-CRT parameters, major pathologic response (P = 0.001), and the absence of lymphatic (P&amp;lt;0.001)/ vascular (P= 0.025)/ perineural invasion (P = 0.001) was associated with longer RFS. For 71 patients with available paired pre- and post-CRT tissues, the changes of protein expression were calculated. The pre-CRT/post-CRT ratio of DHFR (&amp;gt;1.1), Her2 (&amp;lt;1.25), MET (≥0.8), p16 (&amp;lt;2), TK1 (≥0.9) showed trend toward long RFS. Multivariate analysis showed that the presence of lymphatic invasion (HR=3.07; 95% CI, 1.35-7.01; P = 0.008) and pre-CRT high EGFR level (≥200amol/ug; HR=2.23; 95% CI, 1.03-4.83; P = 0.042) were significantly associated with shorter RFS. The presence of lymphatic invasion (P=0.005), positive pre-CRT TYMS level (P = 0.008), and high CEA level (P = 0.015) were significantly related to short survival. Conclusions: Quantitative MS-based proteomics can facilitate the identification of predictive biomarkers of CRT responses and prognosis in LARC patients. Citation Format: Ho Jung An, Ji-Han Jung, Byoung Yong Shim, Hyung Soon Park, Hyeon-Min Cho, Hyung-Jin Kim, Ri Na Yoo, Sung Hwan Kim, Jonghoon Lee, Kang-Moon Lee, Dae Bum Kim, Ji Min Lee. Clinical application of quantitative multiplex mass spectrometry-based proteomics in predicting clinical outcomes in locally advanced rectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4898.

Colorectal cancer in young patients: An institutional experience.

e15140 Background: The incidence of colorectal cancer (CRC) in young patients (&lt;50 years) is increasing but little is known about disease characteristics and treatment outcomes in this patient population. Methods: CRC patients diagnosed at &lt; 50 years of age (UF registry 2000-2017) constituted the IRB approved study cohort. Statistical methods included descriptive statistics, uni-variable cox proportional hazard regression model, Pearson chi-square exact and Wilcoxon rank-sum test. Results: Young CRC patients (n= 286) comprised 16% of total CRC patients (n= 1806) treated at our institution. (See Table for demographics and tumor characteristics). The median age at diagnosis was 45 years (range 17-50) with 74% diagnosed between age 40-50. One third (35.7%) of patients had rectal primary. DNA mismatch repair gene deficiencies (dMMR) and/or microsatellite instability (MSI) was tested in 60.1%; 10.5% had MSI-H or dMMR tumors and 11 of those had confirmed Lynch syndrome. Next generation sequencing (n= 71) or mutational analysis (n= 79) was performed. Most common mutation was exon 12 of K- ras (40.7%, n = 61) followed by TP53 (7.33%; n = 11) and PIK3CA (5.33%; n = 8). BRAF V600E was seen in 5 patients. Patients who underwent curative resections had better hemoglobin (p=0.005), albumin levels (p &lt;0.001) and lower CEA level (p&lt;0.001). Factors associated with poor survival were low albumin ≤34 g/l, advanced primary tumor (T3/T4), nodal disease (N1/N2) and presence of diffuse metastases. For stage 4 disease, the cancer-specific survival (CSS) at 1 year was 77.2%, 3-year CSS was 46.1% and 5-year CSS was 29%; survival was better (HR=0.4; 95% CI 0.2-0.6, p&lt;0.001) among patients who underwent metastatectomy. Conclusions: Our results reveal that the most young CRC were 40-50 years age group with a female preponderance. Young CRC patients were more likely to be managed in an aggressive manner with a higher proportion of early stage patients receiving perioperative therapy. A suggestion of an improved CSS was seen in advanced stage disease even with similar prognostic factors. Review of larger data sets are warranted. [Table: see text]

Disease characteristics and treatment outcomes of young colorectal cancer patients.

691 Background: The incidence of colorectal cancer (CRC) in young patients (&lt; 50 years) is increasing but little is known about disease characteristics and treatment outcomes in this patient population. Methods: CRC patients diagnosed at &lt; 50 years of age (UF institutional registry 2000-2017) constituted the IRB approved study cohort. Statistical methods included descriptive statistics, uni-variable cox proportional hazard regression model, Pearson chi-square exact and Wilcoxon rank-sum test. Results: The median age at diagnosis was 45 years (range 17-50, n = 286) with 212 (74%) diagnosed between age 40-50. One third (35.7%) of patients had rectal primary and most common histology was adenocarcinoma (ACa, 84.6%) and 20% of those had poorly differentiated tumor. More than half of patients had an advanced primary (T3/T4, 65%) and 44% had lymph node positive disease. A trend towards increased delivery of perioperative therapy was seen in early staged disease. (See table) Patients who underwent curative resections had better hemoglobin (p = 0.005) and albumin levels (Alb, p &lt; 0.001) and lower CEA level (p &lt; 0.001). Factors associated poor survival were low alb levels ≤ 34 g/l, advanced primary tumor (T3/T4), nodal disease (N1/N2) and presence of diffuse metastasis. For stage 4 disease, the cancer-specific survival (CSS) at 1 year was 77.2%, 3-year CSS was 46.1% and 5-year CSS was 29%; survival was better (HR = 0.4; 95% CI 0.2-0.6, p &lt; 0.001) among patients who underwent metastatectomy. Conclusions: Our data suggests that younger CRC patients were more likely to be managed in an aggressive manner with a higher proportion of early stage patients receiving perioperative therapy. A suggestion of an improved CSS was seen in advanced stage disease even with similar prognostic factors. Review of larger datasets are warranted. [Table: see text]

Left-sided primary tumor is a favorable prognostic factor for metastatic colorectal cancer patients receiving surgery

ObjectiveThe role of surgery in metastatic colorectal cancer (mCRC) remains controversial. This study was performed to assess the impact of surgery on survival in metastatic colorectal cancer.Materials and MethodsInformation of mCRC patients diagnosed between January 1, 2004, and December 31, 2013, was retrieved from the Surveillance, Epidemiology, and End Results Program database. Patients were classified in three groups: patients undergoing resection of both primary and distant metastatic tumors (group ‘PMTR’), patients receiving primary tumor resection alone (group ‘PTR’) and patients not undergoing any surgery (group ‘No resection’). Kaplan-Meier method and multivariate Cox proportional hazard regression analysis were applied to estimate disease specific survival time (DSS) and determine prognostic factors.ResultsA total of 38,591 mCRC patients were eligible. Overall, median DSS of group ‘PMTR’ was significantly longer compared with group ‘PTR’ and group ‘No resection’ (28.0 vs 21.0 vs 11.0 months, P < 0.001). Stratified analysis observed that primary tumor in left-sided colorectal cancer (LCRC) was a favorable prognostic factor compared with right-sided colorectal cancer (RCRC) (median DSS of LCRC: PMTR, 34 months, PTR, 25 months, No resection, 13 months; median DSS of RCRC: PMTR, 20 months, PTR, 16 months, No resection, 8 months; P < 0.001). Multivariate analysis demonstrated that surgery was an independent prognostic factor for better survival (PMTR, HR = 0.403, 95% CI 0.384–0.423, P < 0.001; PTR, HR = 0.515, 95% CI 0.496–0.534, P < 0.001). Furthermore, in patients undergoing surgery, patients with younger age, female, married status, LCRC and lower CEA level were prone to receiving PMTR.ConclusionsThis analysis demonstrated that surgery was an independent prognostic factor for improved survival in mCRC. Patients with LCRC had better survival than patients with RCRC after surgery.

Prognostic factors of trastuzumab-based chemotherapy in patients with advanced HER2 positive gastric cancer.

41 Background: Prognostic factor in patients with HER2 positive gastric cancer who received trastuzumab (T-mab) based chemotherapy remains unclear. The aim of this study is to reveal the clinical factors which predict prognosis in T-mab based chemotherapy. Methods: We retrospectively reviewed HER2 positive gastric cancer patients treated with T-mab based chemotherapy in our institute from March 2011 to June 2016. Patients’ demographics according to the ToGA study and laboratory data were examined. Results: Total of 143 patients were enrolled. Median follow-up period was 14.9 months, and median progression-free survival (PFS) and overall survival (OS) were 11.2 months (95% CI: 8.6-13.9) and 20.9 months (95% CI: 16.6-25.2), respectively. In univariate analysis, performance status (0 vs. 1-2), present of measurable lesion, presence of visceral metastases, No. of metastatic lesion (1-4 vs. &gt; 4), LDH, ALP, Alb, median CEA (≧ 13.6 mg/ml vs. &lt; 13.6mg/ml), and median Neutrophil/Lymphocyte (N/L) ratio (≧ 3.11 vs. &lt; 3.11) were significantly associated with PFS. Regarding OS, extension of disease (locally advanced vs. metastatic), presence of visceral metastases, No. of metastatic lesions, Hb, ALP, Alb, CRP, median CEA and median N/L ratio were significant. In multivariate analysis, CEA levels (HR 0.54: 95%CI 0.34-0.86, p = 0.010) and ALP (HR 0.57: 95%CI 0.33-0.99, p = 0.046) retained to be significant in regard to PFS. Patients with &lt; median CEA level had a median PFS of 13.1 months vs. 7.2 months with ≧ median CEA level. Patients with normal level of ALP showed a median PFS of 12.8 months vs. 5.9 months with abnormal ALP level. With respect to OS, CEA levels (HR 0.59: 95%CI 0.34-1.03, p = 0.061) and N/L ratio (HR 0.55: 95%CI 0.29-1.06, p = 0.074) were marginally significant. Patients with &lt; median CEA level had a median OS of 27.6 months vs. 17.6 months with ≧ median CEA level. Patients with &gt; median N/L had a median OS of 24.5 months vs. 16.5 month with ≧ median N/L. Conclusions: Lower CEA levels and normal ALP levels were associated with favorable PFS, and lower CEA and N/L ratio were marginally associated with favorable OS.

Perioperative circulating tumor cells in surgical patients with non-small cell lung cancer: does surgical manipulation dislodge cancer cells thus allowing them to pass into the peripheral blood?

We herein evaluated the status of circulating tumor cells (CTC) dislodged from the tumor during surgery in patients who underwent pulmonary resection for non-small cell lung cancer (NSCLC) to assess the clinical implications. Tumor cells in the peripheral arterial blood before surgery (Before) and immediately after lung resection (After) and in the blood from the pulmonary vein of the resected lung were detected using a size selective method. The clinicopathological characteristics and the prognosis were then analyzed according to the CTC status: no tumor cells detected (N), single tumor cell or total number less than 4 cells (S), and existence of clustered cells (C). According to the CTC status, the patients were classified into the following three groups: Before-C and After-C, Group I (n=6); Before-S or N and After-C, Group II (n=9); and Before-S or N and After-S or N, Group III (n=8). Group III showed a high rate of p-stage IA, smaller tumor size, lower CEA level, lower SUVmax level, and a higher relapse-free survival rate than the other groups. CTCs were detected in patients after undergoing lung resection, some of which may have been dislodged by the surgical procedure. The presence of clustered CTCs after the operation indicated an unfavorable outcome.

Mild to moderate increase of serum calcitonin levels only in presence of large medullary thyroid cancer deposits

Many open questions remain to be elucidated about the diagnosis, treatment and prognosis of medullary thyroid cancer (MTC). The most intriguing concerns the outcome of MTC patients after surgery. Great importance is usually given to serum calcitonin (Ct) and carcinoembryonic (CEA) levels. It is commonly believed that the higher are the levels of these tumor markers and their kinetics (double time and velocity of markers levels) the worst is the prognosis. However, this is not the rule, as there are huge MTC metastatic deposits characterized by low serum Ct and CEA levels, and this condition is not closely related to the outcome of the disease during post-surgical follow-up. A series is reported here of patients who have these characteristics, as well as a description of their prognosis and clinical outcome.