Postoperative CEA Research Articles

9189 Medullary Thyroid Cancer Due To A Novel Ret Oncogene Mutation In A Patient On Glp-1 Receptor Agonist

Abstract Disclosure: K. Lamar: None. D. John: None. O. Faour: None. N. Meda: None. M. Kinaan: None. Introduction: Mutations in the RET oncogene have been associated with increased risk of endocrine neoplasia and Medullary Thyroid Cancer (MTC). We report the case of a patient who has a (c.3281G>A) RET mutation, previously reported as a variant of uncertain significance. Case: A 51-year-old lady presented to our endocrine clinic for routine management of hypothyroidism, type 2 diabetes mellitus, and obesity. She had been on liraglutide, metformin, glipizide, and basal insulin for several years with good diabetes management. She had also been on levothyroxine for more than 10 years. On physical examination, a right thyroid lobe nodule was palpated. We performed a neck ultrasound which revealed a solid, isoechoic nodule measuring (1.23 x 1.42 x 2.00 cm) with no calcifications. Fine needle aspiration was consistent with MTC. She denied family history of thyroid cancer. She was advised to stop liraglutide immediately given risk of MTC with GLP-1 receptor agonist use. Preoperative calcitonin and CEA were markedly high at 935 pg/mL and 60.3 ng/mL, respectively. Fortunately, Gallium Ga-68 dotatate PET CT showed no signs of metastatic disease. The patient underwent a total thyroidectomy with bilateral central and lateral neck dissection. No cervical metastases were noted on lymph node dissection. Genetic tumor testing demonstrated a mutation in the RET oncogene (c.3281G>A), which was previously reported as a variant with unknown significance. Screening for hyperparathyroidism and pheochromocytoma was normal. Postoperative calcitonin and CEA were <2.0 pg/mL and 3.2 ng/mL respectively. The patient continues MTC surveillance under the care of a multidisciplinary team. Discussion: Our case is the first case in literature that identifies the RET oncogene (c.3281G>A) mutation as a pathogenic variant associated with MTC. It also emphasizes the need for close monitoring for thyroid nodules in patients on GLP-1 receptor agonists and pre-existing thyroid disease, through a comprehensive physical examination and neck ultrasound if needed. Presentation: 6/2/2024

Sporadic and Familial Medullary Thyroid Carcinoma: A Retrospective Single Center Study on Presentation and Outcome

ABSTRACT Background Medullary Thyroid Carcinoma (MTC) is a neuroendocrine tumor that arises from the thyroid C-cells. Most cases are sporadic (sMTC) while, approximately 25%, are hereditary (hMTC) due to germline mutations of REarranged during Transfection (RET) gene mutations and manifest in the framework of multiple endocrine neoplasia (MEN) 2A or 2B, or as pure familial MTC syndrome (FMTC). Objective The aim of this study is to evaluate the clinical, histopathological, biochemical and outcome differences between sMTC and hMTC. Methods Retrospective analysis of a consecutive series of 102 patients with histologically proven MTC diagnosed in the period between 2000 and 2022. For the analysis patients with MTC diagnosed during screening through genetic test were excluded. Results Patients with hMTC had higher incidence of multifocal and bilateral MTC and younger age at diagnosis. We did not found differences on tumor stage at diagnosis between sMTC and hMTC, such as time to progression and rate of persistent and recurrent disease. At univariate analysis, factors associated with persistent and recurrent disease during follow-up in patients with sMTC were tumor size, extrathyroidal extension, presence of lymph node metastases at diagnosis, pre- and post-operative calcitonin, post-operative CEA; in patients with hMTC, features associated with persistent and recurrent disease were lymph node metastases, post-operative calcitonin and pre- and post-operative CEA values. Conclusion Patients with hMTC and sMTC had similar histopathological characteristics and clinical outcome.

Recurrence of Breast Cancer Among Bangladeshi Women Using Two Serum Protein Tumor Markers, Carcinoembryonic Antigen (CEA) and Carbohydrate Antigen 15-3 (CA15-3): A Prospective Observational Study

Patients with breast cancer may develop recurrence even after adequate primary therapy. Besides clinical examination and imaging, serum protein tumor markers (SPTMs) measurements are used for follow-up. To find out the association of two postoperative SPTMs (e.g., Carcinoembryonic antigen/CEA, Carbohydrate antigen15-3/CA15-3) with the future recurrence of breast cancer among Bangladeshi women. Prospective-observational study was conducted among purposively-selected one hundred Patients (who underwent surgery before six months) during their routine follow-up visit to an oncology/surgical setting in Dhaka Medical College Hospital, Bangladesh. Postoperative CEA (cut-off:5ng/mL) and CA15-3 (30 U/mL) were measured at a single point time by ‘chemiluminescent Immuno assay.' Patients were then followed up for one year to detect any recurrence. Quantitative and categorical variables were compared by Student’s t-test and Fisher’s exact test, respectively. Sensitivity, specificity, and AUC (Area under the curve) of both SPTMs were estimated. Most (64%) of the patients were postmenopausal (Mean-age: 49.8±12.1) with elevated CA15-3 (32%) and CEA (18%). Overall recurrence was 18%, and only CA15-3 was found to be associated with visceral (hepatic and bone) recurrence (P=0.015). The sensitivity and specificity of CEA and CA15-3 were 22.22%, 82.9%, and 66.7%, 75.6%, respectively, while combined sensitivity increased by 6.25%. The AUC of the receiver operating characteristics (ROC) curves were 0.62, 0.82, and 0.88 for CEA, CA15-3, and combination, respectively. Postoperative CA15-3 has been shown to have the capacity to rule out visceral recurrence with a reasonably high probability. Since the specificity of CA15-3 is pretty good, it may detect early recurrence following primary treatment of carcinoma breast.

Persistent high levels of carcinoembryonic antigen after tumor resection are associated with poorer survival outcomes in patients with resected colon cancer

BackgroundInterindividual survival and recurrence rates in cases of locoregional colon cancer following surgical resection are highly variable. The aim of the present study was to determine whether elevated pre-operative and post-operative CEA values are useful prognostic biomarkers for patients with stage I-III colon cancer who underwent surgery with curative intent.MethodsWe conducted a retrospective study in patients with histologically confirmed stage I-III primary colonic adenocarcinoma who underwent radical surgical resection at Mexico’s National Cancer Institute, between January 2008 and January 2020. We determined pre-operative and post-operative CEA and analyzed the association of scores with poorer survival outcomes in patients with resected colon cancer, considering overall survival (OS) and disease-free survival (DFS).ResultsWe included 640 patients with stage I-III colon cancer. Pre-operative CEA levels were in the normal range in 460 patients (group A) and above the reference value in the other 180. Of the latter, 134 presented normalized CEA levels after surgery, but 46 (group C) continued to show CEA levels above the reference values after surgery. Therefore, propensity score matching (PSM) was carried out to reduce the bias. Patients were adjusted at a 1:1:1 ratio with 46 in each group, to match the number in the smallest group. Median follow- up was 46.4 months (range, 4.9–147.4 months). Median DFS was significantly shorter in Group C: 55.5 months (95% CI 39.6–71.3) than in the other two groups [Group A: 77.1 months (95% CI 72.6–81.6). Group B: 75.7 months (95% CI 66.8–84.5) (p-value < 0.001)]. Overall survival was also significantly worse in group C [57.1 (95% CI 37.8–76.3) months] than in group A [82.8 (95% CI 78.6–86.9 months] and group B [87.1 (95% CI 79.6–94.5 months] (p-value = 0.002). To identify whether change in CEA levels operative and post-surgery was an independent prognostic factor for survival outcomes, a Cox proportional hazard model was applied. In multivariate analysis, change in CEA level was a statistically significant, independent prognostic factor for overall survival (p-value = 0.031).ConclusionsWhen assessed collectively, pre-operative and post-operative CEA values are useful biomarkers for predicting survival outcomes in patients with resected colon cancer. Prognoses are worse for patients with elevated pre-operative and post-surgical CEA values, but similar in patients with normal post-surgical values, regardless of their pre-surgery values.

Effect of High-Versus Low-Frequency of Abdominopelvic Computed Tomography Follow-Up Testing on Overall Survival in Patients With Stage II Or III Colon Cancer

BackgroundIntensive surveillance of colon cancer by using the abdominopelvic computed tomography (AP-CT) is common in real world practice; however, it is still unclear whether high-frequency surveillance using AP-CT in patients with these risk factors is superior to that in the low-frequency surveillance. Patients and MethodsWe retrospectively reviewed 1803 patients with stage II-III colon cancer receiving curative surgery between January 1, 2005 to December 31, 2015. We evaluated the average scan-to-scan intervals of postoperative AP-CT testing and assigned patients with an interval of 5 to 8 and 9 to 13 months to the high-frequency (HF) and low-frequency (LF) groups, respectively. The cutoff value of preoperative and postoperative CEA levels was 5 ng/mL. We also applied propensity score matching (PSM) and inverse probability of treatment weighting to adjust clinicopathologic differences between the 2 groups. ResultsWe matched 1:1 for each surveillance group yielding a cohort of 776 matched patients. After PSM, Baseline demographics were overall well balanced between 2 groups. Stage III (OR, 2.00; 95% Confidence interval [CI], 1.21-3.30) and postoperative CEA elevation (OR, 2.30; 95% CI, 1.08-4.92) were independent risk factors of recurrence in multivariate analyses. Patient in the HF group had more surgery plus chemo- or radiotherapy as postrecurrence treatment than patient in the LF group (46.2% vs. 23.1%, P = .017). This trend was retained after PSM, although it is not significant (44.4% vs. 23.1%, P = .060). However, survival outcomes of high-frequency AP-CT surveillance were not superior to those of low-frequency surveillance in all subgroups, including stage III (HR 0.99, 95% CI 0.40-2.47) and postoperative CEA elevation (HR 1.36, 95% CI 0.45-4.11). ConclusionHigh-frequency AP-CT testing is associated with a higher proportion of surgery plus chemo- or radiotherapy as postrecurrence treatment, without improvement in 5-year overall survival.

Prognostic significance of increased preoperative red cell distribution width (RDW) and changes in RDW for colorectal cancer.

Increased preoperative red cell distribution width (RDW) is associated with poor prognosis in several cancers, but the relationships between preoperative RDW and changes in RDW (ΔRDW) and colorectal cancer (CRC) prognosis remain unclear. Our study aimed to demonstrate the prognostic significance of increased preoperative RDW and ΔRDW for CRC. In this retrospective analysis, we enrolled 833 patients who underwent CRC surgery between 2015 and 2019 at the Affiliated Hospital of Xuzhou Medical University, China. ΔRDW in our study was defined as RDW at 1 month after discharge minus preoperative RDW. According to receiver operating characteristic (ROC) curve analysis, we used cut-off values of 13.5% for RDW, 0.9% for ΔRDW. The cumulative survival rate was determined using the Kaplan-Meier method, and significant differences were evaluated by the log-rank test. Multivariable Cox regression model was applied to clarify the independent risk factors for overall survival (OS), which were used to construct a nomogram prediction model. The competing risk method was also applied, and we analyzed only patients with early-stage disease (stage 0-II) for sensitivity analysis. Multivariable Cox regression analysis demonstrated that age, RDW, ΔRDW, postoperative adjuvant chemotherapy, CEA, CA19-9, ASA, TNM stage, and pathological type were independent factors for OS in CRC patients (all p < 0.05). These prognostic factors were used to establish and verify the OS nomogram. Poorer OS was linked to higher RDW (HR = 1.52; 95% CI, 1.11-2.08; p < 0.01) and ΔRDW (HR = 1.65; 95% CI, 1.19-2.28; p < 0.01) in all-stage patients, and was only linked to higher RDW in early-stage patients. In competing risk model, H-RDW and H-ΔRDW were confirmed to be independent risk factors for CSS in CRC patients. High preoperative RDW and ΔRDW are both risk factors for OS and CSS in CRC.

Postoperative circulating tumor DNA testing based on tumor naïve strategy after liver metastasis surgery in colorectal cancer patients.

There is still a lack of highly sensitive methods for monitoring recurrence of colorectal cancer patients after liver metastasis surgery. The aim of this study was to evaluate the prognostic value of tumor-naive ctDNA detection after resection of colorectal liver metastases (CRLM). Patients with resectable CRLM were prospectively enrolled. Based on the tumor-naive strategy, NGS panels containing 15 colorectal cancer hotspot mutated genes were used to detect ctDNA 3-6 weeks after surgery. A total of 67 patients were included in the study, and the positive rate of postoperative ctDNA was 77.6% (52/67). Patients with positive ctDNA had a significantly higher risk of recurrence after surgery (HR 3.596, 95% CI 1.479 to 8.744, P = 0.005), and a higher proportion relapsed within 3 months after surgery (46.7% vs 3.8%). The C-index of postoperative ctDNA in predicting recurrence was higher than that of CRS and postoperative CEA. The nomogram combining CRS and postoperative ctDNA can improve the accuracy of recurrence prediction. Tumor-naive ctDNA detection can detect molecular residual lesions in patients with colorectal cancer after liver metastasis, and its prognostic value is superior to conventional clinical factors.

The İmportance of tumor markers in patients undergoing resection for lung metastasis of colorectal carcinoma

In patients with suitable conditions, complete resection is a potential curative treatment for lung metastases of colorectal cancers (CRC). Various prognostic factors affecting survival have been reported in these patients. In our study, the prognostic significance of CEA and CA19-9 tumor markers in patients who underwent lung resection for CRC metastasis was researched. Fifty-three patients who underwent lung resection for CRC metastasis between January 2015 and July 2021 were included in the study. The relationship between preoperative and postoperative CEA and CA19-9 values, survival times, tumor size, and preoperative CEA and CA19-9 levels were investigated. Patients with high preoperative and postoperative CEA had shorter survival (OS) compared with patients with lower values (p≤0.001 and p= 0.009, respectively). Disease-free survival (DFS) was also shorter in patients with higher preoperative CEA values (p= 0.008). For patients with higher preoperative and postoperative CA 19-9 values, OS and DFS were shorter (p= 0.013 and p≤0.001) and (p= 0.042 and p≤0.001), respectively. There was a weak positive correlation between preoperative CEA value and tumor size (p= 0.008, Pearson correlation coefficient =0.360). However, a strong positive correlation between preoperative CA19-9 value and tumor size was discovered (p≤0.001, Pearson correlation coefficient =0.603). In our study, it was shown that preoperative-postoperative CEA and CA19-9 levels in patients with metastatic colon carcinoma are associated with overall survival.

The T-CEA score: a useful prognostic indicator based on postoperative CEA and pathological T4 levels for patients with stage II-III colorectal cancer.

To investigate a prognostic score for stage II-III colorectal cancer (CRC) based on post-CEA and pT4 levels. Two cohorts of stage II-III CRC patients who underwent curative surgery between 2011 and 2017 were included. The prognostic score (T-CEA score) was calculated as follows: T-CEA-0, post-CEA ≤ 5ng/mL and pT1-3; T-CEA-1, post-CEA > 5ng/mL or pT4; T-CEA-2, post-CEA > 5ng/mL and pT4. The T-CEA scores of the 587 patients were as follows: T-CEA-0 (n = 436; 74%), T-CEA-1 (n = 129; 22%), and T-CEA-2 (n = 10; 2%). The 5-year recurrence-free survival (RFS) rates of the T-CEA-0, 1, and 2 groups were 80.3%, 54.8%, and 0%, respectively (P < 0.01), and the 5-year overall survival (OS) rates were 90.9%, 74.2%, and 0%, respectively (T-CEA-0 vs T-CEA-1: P < 0.01, T-CEA-1 vs T-CEA-2: P = 0.04). Multivariate analysis revealed that an elevated T-CEA score of 1 or 2 was a significant risk factor for poor RFS (HR: 2.89, P < 0.01) and OS (HR: 2.85, P < 0.01). The T-CEA score is a reliable and convenient prognostic score for stage II-III CRC.

Lobaplatin-based prophylactic hyperthermic intraperitoneal chemotherapy for T4 gastric cancer patients: A retrospective clinical study.

To explore the clinical efficacy of lobaplatin-based prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with T4 gastric cancer after surgery and to evaluate its impact on survival. Data on patients with T4 gastric cancer who underwent radical gastric resection between March 2016 and August 2017 were collected from the National Cancer Center and Huangxing Cancer Hospital. Enrolled patients were divided into two groups according to receiving or not receiving HIPEC. A total of 106 patients were included in this study; among them, 51 patients underwent radical gastric resection plus prophylactic HIPEC, and 55 patients underwent radical gastric resection only. The baseline characteristics were well balanced between the two groups. The postoperative platelet counts in the HIPEC group were significantly lower than those in the non-HIPEC group (P< 0.05); however, we did not observe any occurrences of serious bleeding in the HIPEC group. There were no significant differences in the postoperative complication rates between the two groups (P > 0.05). The postoperative (1 month) CEA, CA19-9, and CA72-4 levels in the HIPEC group were significantly decreased in the HIPEC group (P < 0.05). At a median follow-up of 59.3 months, 3 (5.5%) patients in the HIPEC group experienced peritoneal recurrence, and 10 (18.2%) patients in the non-HIPEC group experienced peritoneal recurrence (P < 0.05). Both groups had comparable 5-year overall survival (OS) rates (41.1% HIPEC group vs. 34.5% non-HIPEC group, P = 0.118). The 5-year disease-free survival was significantly higher in the HIPEC group than in the non-HIPEC group (28.6% versus 39.7%, p = 0.046). Lobaplatin-based prophylactic HIPEC is feasible and safe for patients with T4 gastric cancer and does not increase postoperative adverse effects. The use of HIPEC showed a significant decrease in the incidence of local recurrence rates and blood tumor marker levels. The 5-year disease-free survival was significantly higher in the HIPEC group; however, the 5-year OS benefit was not found in T4 stage patients.

Risk Factors of Colorectal Cancer Recurrence After Curative Resection Surgery: A Systematic Review and Meta-analysis

Context: According to the World Health Organization, colorectal cancer (CRC) is the third most prevalent cancer globally, with the highest mortality rate after lung cancer. Some studies predicted risk factors provoking CRC recurrence. However, no single study discussed CRC recurrence. Objectives: This study aimed to quantitatively estimate the influence of several risk factors toward early recurrence of CRC. Methods: We utilized four medical databases, including Pubmed, Cochrane, Wiley library, and ScienceDirect, and a range of literature searches between July to October 2020 with output study, odds ratio (OR), and some risk factors. We used PRISMA protocol along with several relevant keywords with NOS method was utilized to assess the quality of the study. Fixed- and randomized effect model were utilized to control each numerical analysis’ bias. Results: We found six studies that compared the risk factor of CRC recurrence after curative resection with curative-intention encompassing a total of 15.457 patients. We found seven risk factors of colorectal cancer recurrence, including vascular invasion (OR 2.3; IK95%: 01.56 - 3.4; P &lt; 0.0001), depth of invasion (T stage) (OR 2.27; IK95%: 1.14 - 4.51; P = 0.02), pre-operative CEA serum (OR 2.24 IK95%: 1.57 - 3.2; P &lt; 0.0001), post-operative CEA serum (OR 5.97 IK95%: 3.04 - 11.74; P &lt; 0,0001), pre-operative CA19-9 serum (OR 3.03; IK95%: 1.74 - 5.25; P &lt; 0.0001), and regional nodal metastasis (N stage) (OR 2.56; IK95% 1.41 - 4.62; P = 0.002). Conclusions: Risk factors of earlier CRC recurrence were diversely reviewed. The elevation of post-operative CEA serum was assumed as the main factor in this study; however, most of the studied parameters were statistically significant.

Factors Associated With Abnormal Joint Contact Pressure After Periacetabular Osteotomy: A Finite-Element Analysis

BackgroundIdentifying factors associated with poor hip contact mechanics after periacetabular osteotomy (PAO) may help surgeons optimize acetabular corrections in individual patients. We performed individual-specific finite-element analyses to identify preoperative morphological and surgical correction factors for abnormal contact pressure (CP) after PAO. MethodsWe performed finite-element analyses before and after PAO with reference to the standing pelvic position on individual-specific 3-dimensional hip models created from computed tomography images of 51 dysplastic hips. Nonlinear contact analyses were performed to calculate the joint CP of the acetabular cartilage during a single-leg stance. ResultsThe maximum CP decreased in 50 hips (98.0%) after PAO compared to preoperative values, and the resulting maximum CP was within the normal range (<4.1 MPa) in 33 hips (64.7%). Multivariate analysis identified the roundness index of the femoral head (P = .002), postoperative anterior center-edge angle (CEA; P = .004), and surgical correction of lateral CEA (Δlateral CEA; P = .003) as independent predictors for abnormal CP after PAO. A preoperative roundness index >54.3°, a postoperative anterior CEA <36.3°, and a Δlateral CEA >27.0° in the standing pelvic position predicted abnormal CP after PAO. ConclusionPAO normalized joint CP in 64.7% of the patients but was less likely to normalize joint CP in patients with aspheric femoral heads. Successful surgical treatment depends on obtaining adequate anterior coverage and avoiding excessive lateral correction, while considering the physiological pelvic tilt in a weight-bearing position.

Role of Serum Carcinoembryonic Antigen in Predicting Recurrent Disease following Curative Resection of Rectal Cancer.

Srikanth SomaIntroduction Surveillance of patients following definitive treatment of rectal malignancy is based on the predicament that early detection of recurrence may provide an opportunity for cure. Available methods for monitoring include clinical, radiological, and serum tests. The purpose of this study was to determine the effectiveness of CEA in detecting recurrences. Materials and Methods Retrospective analysis of patients with adenocarcinoma rectum treated with curative intent between 2012 to 2020 at our institute was performed. Postoperatively, patients were followed with CEA measurements according to our institution protocol and elevation of serum CEA above 5 ng/dL was considered as suspicious of recurrence. Results One hundred ninety patients who received curative treatment were deemed eligible for the analysis. Among these 61 patients had recurrences during the follow-up period and postoperative CEA measurements at the time of recurrence were analyzed in all the patients. Sensitivity, specificity, positive predictive value, and negative predictive value of postoperative CEA to detect recurrences are 81.9, 92.2, 83.3, and 91.5%, respectively. Conclusion CEA surveillance following definitive management of rectal cancer detects recurrences in majority of the patients and hence strongly recommended.

Impact of postoperative integrated genomic and epigenomic signatures of circulating tumor DNA (ctDNA) on recurrence in resected colorectal cancer: Initial report of a prospective ctDNA monitoring study COSMOS-CRC-01.

168 Background: Identifying molecular residual disease (MRD) using circulating tumor DNA (ctDNA) analysis after curative surgery can potentially stratify the recurrence risk and facilitate personalization of adjuvant treatment in patients with colorectal cancer (CRC). We conducted a prospective study “COSMOS-CRC-01” to evaluate the utility of a plasma-only ctDNA assay integrating genomic and epigenomic signatures. Methods: Patients with resectable clinical stage 0–III colorectal cancer were eligible. Plasma samples were collected at structured pre- and post-surgical timepoints and analyzed using Guardant Reveal, a plasma-only ctDNA assay that detects the presence of MRD by identifying somatic alterations and methylation signatures of cell-free DNA associated with colorectal cancer. Results: As of April 2021, 501 patients were enrolled in the COSMOS-CRC-01, of which 496 patients had their post-operative 4-week ctDNA status. In this analysis, we included the first 100 patients enrolled with clinical stage II or more CRC. Seven patients were excluded due to non-curative resection or pathological stage (pStage) IV. The assay was able to produce a result for all 93 samples analyzed (failure rate of 0%). MRD was detected in 23 (25%) patients 4 weeks after surgery. The MRD detection rate was 20% in pStage II disease and 29% in pStage III disease. Patients with positive MRD were older than those with negative MRD ( p = 0.0001). Across all MRD positive samples, 30%, 9%, and 61% were positive by both genomic and epigenomic, only genomic, and only epigenomic calls. Genomic signatures included APC, BRAF, KRAS, and TP53 mutations with the lowest variant allelic fraction of 0.04%. With a median follow-up time of 12.2 months (range 8-18 months), 9 of 93 patients recurred (9.7%). ctDNA was detected from a single 4-week post-surgical sample in 55% of patients who recurred (5 of 9). 1-year disease-free survival was 81.2% in patients with positive MRD and 93.9% in those with negative MRD (hazard ratio 3.49, 95% CI 0.93–13.10, p = 0.049). Multivariate analysis including baseline characteristics associated with recurrence risk showed that MRD status had the strongest association with the recurrence. Post-operative 4-week serum CEA level was not associated with risk for recurrence. Conclusions: While follow-up in this cohort is currently limited, the results suggest that a single post-surgery sample run on a plasma-only assay that integrates genomic and epigenomic signatures can more accurately stratify patients with CRC by recurrence risk than previously known clinical factors. Data from baseline and longitudinal timepoints will be reported as available along with longer term clinical follow-up. Clinical trial information: UMIN000037765.

Association of perioperative serum carcinoembryonic antigen level and recurrence in low-risk stage IIA colon cancer.

The purpose is to investigate prognosis according to serum CEA levels before and after surgery in patients with stage IIA colon cancer who do not show high-risk features. Among the patients diagnosed with colon adenocarcinoma between April 2011 and December 2017, 462 patients were confirmed as low-risk stage IIA after surgery and enrolled. The ROC curve was used to determine cut-off values of pre- and postoperative CEA. Patients were classified into three groups using these new cut-off values. All recurrence occurred in 52 of 463 patients (11.2%). However, recurrence in group H was 15.9%, which was slightly higher than the other two groups (P = 0.04). Group L and M showed 10.5% and 12.8% overall survival, group H was higher at 21.0% (P = 0.005). Recurrence was the only risk factor in group H was significantly higher in group L (HR 2.008, 95% CI, 1.123-3.589, P = 0.019). Mortality was similar to recurrence (HR 1.975, 95% CI 1.091-3.523, P = 0.044). Among patients with low-risk stage IIA colon cancer, recurrence and mortality rates were higher when perioperative serum CEA levels were above a certain level. Therefore, high CEA level should be considered a high-risk feature and adjuvant chemotherapy should be performed.

Prognostic Impact of Carcinoembryonic Antigen Levels in Rectal Cancer Patients Who Had Received Neoadjuvant Chemoradiotherapy.

PurposeCarcinoembryonic antigen (CEA) is a useful marker for rectal cancer. The aim of this study was to investigate the prognostic impact of CEA level according to neoadjuvant chemoradiotherapy (nCRT) in rectal cancer patients who underwent radical surgery.MethodsA total of 245 patients with rectal cancer who underwent radical surgery were retrospectively evaluated. Serum CEA level was measured preoperatively and postoperatively. We compared survival outcomes based on CEA level before and after surgery according to nCRT.ResultsOf the 245 patients, elevation of CEA level was observed preoperatively in 79 and postoperatively in 30, respectively. Eighty-seven (35.5%) patients received nCRT, and elevated CEA level was a significant prognostic factor both before and after surgery. In patients who had not received nCRT, an elevated CEA level was a significant prognostic factor before surgery but was not significant after surgery. In a multivariate analysis for prognostic factors, elevation of preoperative CEA level was an independent prognostic factor of disease-free survival (DFS) regardless of nCRT. Postoperative CEA level was an independent prognostic factor of DFS in patients who had received nCRT but was not a factor in patients who had not received nCRT.ConclusionSerum CEA level was an independent prognostic factor both preoperatively and postoperatively in rectal cancer patients who had received nCRT.

Biochemical and Genomic Changes of a Devastating Metastatic Medullary Thyroid Cancer

Abstract Introduction: Medullary thyroid carcinoma (MTC) is a neuroendocrine tumor of thyroid parafollicular C cells. About 25% of cases are hereditary, associated with MEN2 syndromes. RET M918 mutation (somatic or germline) is associated with the most aggressive form of MTC. If MTC is hereditary, further tumor genomic analysis is not routinely performed. Therefore, the somatic mutational landscape of hereditary MTCs is not frequently described in the literature. We present an unusual case of MTC with a germline M918 RET mutation, displaying an initial smoldering course followed by rapidly fatal widespread metastases. Whole exome sequencing (WES) of primary tumor and metastases revealed intertumoral heterogeneity with many somatic mutations including p53 mutation. Clinical Case: The patient with characteristic facies of MEN 2B presented with a neck mass at age 28. She had no family history of MEN. At diagnosis, calcitonin was 11,392 pg/mL and CEA was 729.7 ug/L. Pathology showed MTCs of 5 cm (right) and 2.1 cm (left) with lymph node metastases (pT3N1bMx). Genetic testing showed RET M918 mutation. Postoperative calcitonin and CEA were 3.3 pg/ml and 1.7 ug/L respectively. Tumor markers doubling time was initially about 1 year, but progressively shortened over time. Three years after surgery, calcitonin and CEA were 101 pg/ml and 387 ug/L respectively. CT chest and abdomen identified no distant metastasis. Over the next 4 months, calcitonin and CEA increased dramatically to 1821pg/ml and 3974 ug/L. The patient was admitted for acute liver failure and passed away. Autopsy revealed widely metastatic disease to liver, lungs, spleen, pituitary, right adrenal gland, bones, and brain. WES revealed 87, 283 and 591 somatic mutations in the primary tumor, lung and liver metastases respectively. The primary tumor had chromosome 1p loss whereas liver and lung metastases had somatic mutation of TP53 and single copy loss of chromosome 17 (biallelic inactivation of p53). Conclusion: This case illustrates intertumoral spatial and temporal genetic heterogeneity. Mutations detected by WES may or may not be cancer-related and their clinical relevance is often uncelar. We hypothesize TP53 biallelic loss might have contributed to the aggressive phenotype of this tumor. Also of note, even before the appearance of metastases, CEA was disproportionately higher than calcitonin, reflecting tumor dedifferentiation. Further studies are needed to address CEA threshold for additional imaging and imaging modality for early detection of metastases.

The Importance of Lymph Node Dissection in Medullary Thyroid Carcinoma Management

Abstract Medullary thyroid carcinoma (MTC) is a rare endocrine malignancy that arises from calcitonin (Ct) parafollicular C-cells. Most cases are sporadic with frequent presentation being a solitary thyroid nodule. Total thyroidectomy with central neck dissection of lymph nodes (LN) is the standard treatment for MTC. The need for lateral neck dissection is controversial, with poor efficacy of non-surgical treatments presenting a problem. We present a case of MTC with preoperative Ct &amp;gt;500 pg/mL and negative imaging for metastases who underwent total thyroidectomy without LN exploration with an excellent postoperative biochemical response. This is a case of a 52-year-old female with a three-year history of anterior neck growth. The repeat fine needle aspiration (FNA) of a, previously negative for malignancy, growing nodule was consistent with MTC. Preoperative Ct and CEA levels were significantly elevated, 834.0 pg/mL and 11.2 ng/dL, respectively; a preoperative pan- CT scan did not reveal any suspicious LN or metastatic lesions and a negative RET oncogene mutation with normal plasma normetanephrines and metanephrines suggested a spontaneous rather than familial MTC. Patient underwent total thyroidectomy without LN exploration. Pathology confirmed MTC stage T1b. The one and three months postoperative follow up showed a significant downtrend with no normalization of Ct and CEA levels, 9.1 – 9.2 and 11.1 – 1.2, respectively. Reoperation for central and lateral neck dissection was considered; however, given the excellent biochemical response as well as the lack of radiographic evidence of disease, it was decided to continue monitoring of Ct and CEA levels for now. MTC response is monitored by the postoperative serum Ct and CEA levels when compared to the preoperative values. Serum Ct serves as a sensitive tumor marker, which is thought to have correlation with malignancy mass size and its cellular differentiation. The term biochemically cured, refers to the postoperative normalization of CEA and undetectable levels of Ct which carries a 5-year recurrence of 5%. It is believed that the higher the levels and the faster doubling time of these tumor markers the worse is the prognosis. In addition, it is suggested that patient’s age and extent of disease at the time of surgery are proportionally correlated with disease recurrence. However, there are reports of large MTC metastatic deposits with low serum Ct and CEA, rising up the hypothesis that levels reflect cell production potential for tumor markers rather than the number of cells. Reoperation rarely results in biochemical cure, but it may slow disease progression. Normal postoperative Ct levels predict cure; however, the clinical course of those with upper normal limit levels postoperatively is markedly variable. Careful regular biochemical and imaging follow-up will be of the utmost importance for the patient presented in this case.

Relationship Between Preoperative and Postoperative Serum Carcinoembryonic Antigen and Prognosis of Patients with Stage I-III Rectal Cancer: A Retrospective Study of a Multicentre Cohort of 1022 Rectal Cancer Patients.

PurposeBased on a multi-centered and a large sample size, this study aims to analyze the relationship between preoperative and postoperative serum CEA and recurrence of rectal cancer without preoperative therapy.MethodsThis retrospective cohort study enrolled stage I to III rectal cancer patients without preoperative therapy (N = 1,022) who received radical resection of rectal cancer from 2 hospitals in China. Based on the preoperative and postoperative serum carcinoembryonic antigen, the patients were subdivided into 3 groups ie, normal preoperative CEA (≤5.0 ng/mL, N = 627), elevated preoperative (>5.0 ng/mL) but normalized postoperative CEA (normalized postoperative CEA, N = 255), as well as elevated preoperative and postoperative CEA (elevated postoperative CEA, N = 67). The generalized additive model was used to assess the relationship between carcinoembryonic antigen and the risk of recurrence. Further, the Cox regression model was used to evaluate the relationship between carcinoembryonic antigen and 3-year recurrence-free survival (RFS) after adjusting for potential confounders.ResultsThe 3-year RFS of patients with elevated postoperative CEA was 45.8% (95% CI, 35.2% −59.5%), which was significantly lower compared to the other two groups of patients (normalized postoperative CEA: 75.9%, 95% CI, 70.8%-81.4%; and normal preoperative CEA: 84.9%, 95% CI, 82.2%-87.8%) (P <0.001). Based on multivariable Cox model analysis, the elevated postoperative CEA was a prognostic factor for 3 years RFS (hazard ratio [HR], 3.08; 95% CI, 2.05–4.66; P<0.001). At the same time, normalized postoperative CEA was insignificantly correlated with 3-year RFS (HR, 1.38; 95% CI, 1.00–1.92; P = 0.05) and was not an independent risk factor.ConclusionWe found that preoperative and postoperative serum CEA of rectal cancer patients were related to the 3-year recurrence-free survival rate. Moreover, the risk of recurrence in the normalized postoperative CEA group of patients was insignificantly different from that of the normalized preoperative CEA patients. Therefore, it is necessary to combine preoperative and postoperative CEA to predict the prognosis of patients with rectal cancer, rather than using it alone.

Circulating tumor DNA analysis for assessment of recurrence risk, benefit of adjuvant therapy, and early relapse detection after treatment in colorectal cancer patients.

11 Background: Timely detection of recurrence, as well as identification of patients at high risk of recurrence after surgery and after completion of adjuvant therapy, are major challenges in the treatment of colorectal cancer (CRC). Postsurgical circulating tumor DNA (ctDNA) analysis is a promising tool for the identification of patients with minimal residual disease (MRD) and a high risk of recurrence. The objective of this prospective, multicenter study was to determine whether serial postsurgical ctDNA analysis could identify the patients at high risk of recurrence, provide an assessment of adjuvant therapy efficacy and detect relapse earlier than standard-of-care radiological imaging. Methods: The cohort comprises 265 stage I-III CRC patients, the to-date largest cohort assessed for ctDNA. All patients had the tumor resected and a subset of 62.6% (166 /265) was additionally treated with ACT. Plasma samples (n = 1503) were collected at various time points for a median follow-up of 28.4 months (range: 1.2-51.0 months). Individual tumors and matched germline DNA were whole-exome sequenced and somatic single nucleotide variants (SNVs) were identified. Personalized multiplex PCR assays were designed to track tumor-specific SNVs (Signatera, bespoke mPCR NGS assay) in each patient’s plasma sample. Results: Postoperative ctDNA status prior to ACT was assessed in 218 patients, of which 9.17% (20/218) were identified to be MRD-positive and 75% (15/20) eventually relapsed. The remaining 25% (5/20) of MRD-positive patients that did not relapse, received ACT. In contrast, only 13.6% (27/198) of MRD-negative cases relapsed (HR: 11: 95% CI: 5.7-20; p &lt; 0.001). Longitudinal ctDNA-positive status, post-definitive therapy (n = 202) was associated with a HR of 36 (95% CI: 16-81; p &lt; 0.001). For a subset of 155 patients postoperative CEA and ctDNA measurements were compared, wherein, ctDNA-positive status was found to be significantly associated with RFS (HR, 7.1; 95% CI, 3.4-15; P &lt; 0.001) compared to CEA (HR, 1.2; 95% CI, 0.46-3.1; P = 0.73). Serial ctDNA analysis detected MRD up to a median of 8 months (0.56 - 21.6 months) ahead of radiologic relapse. Conclusion: Postoperative ctDNA positive status was associated with markedly reduced RFS compared to CEA. The study also shows that effective therapy can be curative in a portion of MRD-positive patients. In a longitudinal setting, ctDNA analysis predicted the risk of recurrence and is a more reliable biomarker for treatment response monitoring.