High CEA Level Research Articles

Association between quantitative CT body composition analysis and prognosis in cetuximab-based first-line treatment for advanced colorectal cancer patients

BackgroundThe objective of this study is to investigate the potential association between change in body composition before and after cetuximab-based therapy and the prognostic outcomes among individuals diagnosed with advanced colorectal cancer.MethodsA retrospective analysis was undertaken on a cohort of 81 patients diagnosed with RAS wild-type (WT) metastatic colorectal cancer (mCRC) who were treated with cetuximab-based first-line therapy. To assess relevant body composition parameters, quantitative computed tomography (QCT) scans were conducted both before and after cetuximab treatment. These parameters encompassed measurements of visceral fat area (VFA), subcutaneous fat area (SFA), total muscle area (TMA) at the third lumbar vertebra level (L3), and bone mineral density (BMD) at the first and second vertebrae levels (L1/2). The skeletal muscle index (SMI) was subsequently calculated, and changes in parameters (∆VFA, ∆SFA, ∆SMI, ∆BMD) were standardized.ResultsThe cut-off values for ∆VFA, ∆SFA, ∆SMI, and ∆BMD were 0.28%, -2.76%, -2.97%, and -7.98%, respectively. CEA, ∆VFA, ∆SMI, and ∆BMD were associated with poor outcomes of cetuximab-based first-line chemotherapy (P < 0.05). The risk of disease progression was higher when ∆VFA < 0.28%, ∆SFA < -2.76%, ∆SMI < -2.97%, and ∆BMD < -7.98%. Multivariate analysis indicated that CEA (HR: 0.396, 95% CI: 0.160–0.980, P = 0.045), ∆VFA (HR: 0.307, 95% CI: 0.145–0.651, P = 0.002), and∆SMI (HR: 0.725, 95% CI: 0.322–1.630, P = 0.001) have significant prognostic value for progression-free survival (PFS) in RAS WT mCRC patients treated with cetuximab-based first-line chemotherapy.ConclusionsCEA, ∆VFA, and ∆SMI are independent predictors for PFS in patients with advanced colorectal cancer. High levels of CEA, ∆VFA, and low levels of ∆SMI may indicate poorer outcomes. CEA, ∆VFA, and ∆SMI can be used to predict PFS in mCRC patients receiving cetuximab-based first-line chemotherapy.Trial registrationThis study was approved by the Ethics Committee of Anhui Provincial Cancer Hospital of Anhui Medical University (Batch No:2024-ZNY-02). All subjects signed an informed consent form.

Survival Outcomes of Durvalumab in Combination with Cisplatin and Gemcitabine in Advanced Biliary Tract Cancer: Real-World Results from a Single Italian Institution

Introduction: The TOPAZ-1 phase III trial showed a survival benefit with durvalumab plus gemcitabine and cisplatin in patients with advanced biliary tract cancer (BTC). To understand this combinationʼs real-world efficacy and tolerability, we conducted a retrospective analysis of its first-line treatment outcomes. Methods: We included patients with unresectable, locally advanced, or metastatic BTC treated with cisplatin, gemcitabine, plus durvalumab. The primary endpoint was overall survival (OS). Results: Thirty-three patients were enrolled. Median OS was NR and median progression free survival (PFS) was 7.6 months, after a median follow-up of 13.5 months. The investigator-assessed overall response rate was 34.5%, with stable disease in 53.0% of patients. High baseline CEA levels were associated with poor survival. Any grade adverse events (AEs) occurred in 97% of patients. Immune-related AEs (irAEs) occurred in 16% (grade >2: 6%). Presence of TP53 mutation was related to a worse OS; conversely the presence of ARID1A genomic alteration was related to a better PFS. A tendence toward a better OS was found for BRCAness patients which did not reach the statistical significance. On the other hand, BRCAness patients showed significantly higher PFS compared to no BRCAness patients. Conclusion: This real-world analysis largely confirmed the TOPAZ-1 findings, supporting gemcitabine, cisplatin, and durvalumab as a first-line standard of care for patients with advanced BTC.

Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer: A large real-life worldwide population

BackgroundThe TOPAZ-1 phase III trial showed a survival benefit with durvalumab plus gemcitabine and cisplatin in patients with advanced biliary tract cancer (BTC). To understand this combination's real-world efficacy and tolerability, we conducted a global multicenter retrospective analysis of its first-line treatment outcomes. MethodsWe included patients with unresectable, locally advanced, or metastatic BTC treated with durvalumab, gemcitabine, and cisplatin at 39 sites in 11 countries (Europe, the United States, and Asia). The primary endpoint was overall survival (OS). Results666 patients were enrolled. Median OS was 15.1 months and median PFS was 8.2 months. The investigator-assessed overall response rate was 32.7 %, with stable disease in 45.2 % of patients. High baseline CEA levels, ECOG PS > 0, metastatic disease, and NLR > 3 were associated with poor survival. Any grade adverse events (AEs) occurred in 92.9 % of patients (grade >2: 46.6 %). Immune-related AEs (irAEs) occurred in 20.0 % (grade >2: 2.5 %). Three deaths (0.5 %) were deemed treatment-related, none linked to immunotherapy. Common irAEs were rash (8.2 % all grades; 0.3 % grade >2), itching (10.3 % all grades; 0.2 % grade >2), and hypothyroidism (5.1 % all grades; 0.3 % grade >2). Durvalumab discontinuation rate due to AEs was 1.5 %.ESMO-recommended genes were analyzed and no outcome differences were found. A comparative analysis with a historical cohort of patients treated with chemotherapy alone confirmed the positive survival impact of durvalumab in combination with cisplatin/gemcitabine. ConclusionThis first global real-world analysis largely confirmed the TOPAZ-1 findings, supporting gemcitabine, cisplatin, and durvalumab as a first-line standard of care for patients with advanced BTC.

Predictors for temporary stomas non-closure among non-metastatic rectal cancer patients undergoing curative resection: a retrospective analysis

BackgroundThe primary treatment for non-metastatic rectal cancer is curative resection. However, sphincter-preserving surgery may lead to complications. This study aims to develop a predictive model for stoma non-closure in rectal cancer patients who underwent curative-intent low anterior resection.MethodsConsecutive patients diagnosed with non-metastatic rectal cancer between January 2005 and December 2017, who underwent low anterior resection, were retrospectively included in the Chang Gung Memorial Foundation Institutional Review Board. A comprehensive evaluation and analysis of potential risk factors linked to stoma non-closure were performed.ResultsOut of 956 patients with temporary stomas, 10.3% (n = 103) experienced non-closure primarily due to cancer recurrence and anastomosis-related issues. Through multivariate analysis, several preoperative risk factors significantly associated with stoma non-closure were identified, including advanced age, anastomotic leakage, positive nodal status, high preoperative CEA levels, lower rectal cancer presence, margin involvement, and an eGFR below 30 mL/min/1.73m2. A risk assessment model achieved an AUC of 0.724, with a cutoff of 2.5, 84.5% sensitivity, and 51.4% specificity. Importantly, the non-closure rate could rise to 16.6% when more than two risk factors were present, starkly contrasting the 3.7% non-closure rate observed in cases with a risk score of 2 or below (p < 0.001).ConclusionPrognostic risk factors associated with the non-closure of a temporary stoma include advanced age, symptomatic anastomotic leakage, nodal status, high CEA levels, margin involvement, and an eGFR below 30 mL/min/1.73m2. Hence, it is crucial for surgeons to evaluate these factors and provide patients with a comprehensive prognosis before undergoing surgical intervention.

Mucin-producing tumors of the ovary——preoperative differentiation between metastatic ovarian mucinous carcinoma and primary mucinous malignant tumors

ObjectiveTo investigate the clinical and magnetic resonance imaging (MRI) features for preoperatively discriminating primary ovarian mucinous malignant tumors (POMTs) and metastatic mucinous carcinomas involving the ovary (MOMCs).MethodsThis retrospective multicenter study enrolled 61 patients with 22 POMTs and 49 MOMCs, which were pathologically proved between November 2014 to Jane 2023. The clinical and MRI features were evaluated and compared between POMTs and MOMCs. Univariate and multivariate analyses were performed to identify the significant variables between the two groups, which were then incorporated into a predictive nomogram, and ROC curve analysis was subsequently carried out to evaluate diagnostic performance.Results35.9% patients with MOMCs were discovered synchronously with the primary carcinomas; 25.6% patients with MOMCs were bilateral, and all of the patients with POMTs were unilateral. The biomarker CEA was significantly different between the two groups (p = 0.002). There were significant differences in the following MRI features: tumor size, configuration, enhanced pattern, the number of cysts, honeycomb sign, stained-glass appearance, ascites, size diversity ratio, signal diversity ratio. The locular size diversity ratio (p = 0.005, OR = 1.31), and signal intensity diversity ratio (p = 0.10, OR = 4.01) were independent predictors for MOMCs. The combination of above independent criteria yielded the largest area under curve of 0.922 with a sensitivity of 82.3% and specificity of 88.9%.ConclusionsPatients with MOMCs were more commonly bilaterally and having higher levels of CEA, but did not always had a malignant tumor history. For ovarian mucin-producing tumors, the uniform locular sizes and signal intensities were more predict MOMCs.

Clinical and immunological characteristics and prognosis of patients with autoantibody negative dermatomyositis: a case control study.

Myositis-specific antibodies (MSAs) and myositis-associated antibodies (MAAs) are associated with distinctive dermatomyositis (DM)clinical phenotypes. The aim of this study is to explicate the clinical andimmunologicalfeatures of MSAs-negative DM patients. A total of 515 individuals diagnosed with DM was screenedfrom 2013 to 2022 and 220 DM patients were enrolled in this retrospective cohort. Clinical and laboratory data of these patients were analyzed. MSAs-negative DMpatients were categorized into two groups: MAAs-negative(MSAs (-)/MAAs (-)) groupand MAAs-positive (MSAs (-)/MAAs (+))group. The percentage of Raynaud's phenomenon (P=0.026) was higher in the MSAs (-)/MAAs (+) DM patients than the MSAs-positiveDM patients and MSAs (-)/MAAs (-) DMpatients. The proportion of rapidly progressive interstitial lung disease (RP-ILD) in the MSAs-negative DM patients was lower than that in the MSAs-positive group. The MSAs (-)/MAAs (+) group had a higher proportion of organizing pneumoniaand usual interstitial pneumonia (P=0.011), and elevated eosinophils in their bronchoalveolar lavage fluid (P=0.008). Counts of lymphocytes (P=0.001) and CD16+CD56+ natural killer (NK) cells (P=0.012) were higher in the MSAs-negative group. Additionally, the percentage of CD4+TNFα+ (P=0.040), CD4+IFNγ+ (P=0.037), and CD4+IL-2+ (P=0.018) cells among totalCD4+ T cells were higher in the MSA-negative DM patients compared with the MSAs-positive DM patients. Besides, MSAs-negative patients demonstrated a more favorable prognosis than MSAs-positive patients. Multivariable regression analysis identified advanced onsetage, higher level ofcarcinoembryonic antigen (CEA), and RP-ILD as risk factors for mortality in DM patients. Compared with MSAs-positive group,MSAs-negative DM patients suffered less from organ involvement compared with MSAs-positive group and tend to have better prognosis. Key Points MSAs-negative DM patients exhibited distinct characteristics in comparison with MSAs-positive DMpatients: • The MSAs (-)/MAAs (+) DM patientsdemonstrated a higher prevalence of organizing pneumonia (OP)and usual interstitial pneumonia (UIP), and elevated eosinophil counts in bronchoalveolar lavage fluid. • CEA levels were lower in MSAs-negative patients compared with MSAs-positive patients. • Elevated counts of lymphocytes and CD16+CD56+ NK cells were identified in the MSAs-negativepatients. Additionally, proportions of CD4+TNFα+, CD4+IFNγ+, and CD4+IL-2+ cells among total CD4+ T cells were higher in the MSAs-negative DM patients compared with DM MSAs-positive DM patients. • MSAs-negative DMpatients had a more favorable prognosis than MSAs-positive DMpatients. A multivariable regression analysis revealed the advanced onsetage, highCEA levels, and RP-ILD were risk factors for mortality in DM patients.

Tumor-associated microbiome features of metastatic colorectal cancer and clinical implications.

Colon microbiome composition contributes to the pathogenesis of colorectal cancer (CRC) and prognosis. We analyzed 16S rRNA sequencing data from tumor samples of patients with metastatic CRC and determined the clinical implications. We enrolled 133 patients with metastatic CRC at St. Vincent Hospital in Korea. The V3-V4 regions of the 16S rRNA gene from the tumor DNA were amplified, sequenced on an Illumina MiSeq, and analyzed using the DADA2 package. After excluding samples that retained <5% of the total reads after merging, 120 samples were analyzed. The median age of patients was 63 years (range, 34-82 years), and 76 patients (63.3%) were male. The primary cancer sites were the right colon (27.5%), left colon (30.8%), and rectum (41.7%). All subjects received 5-fluouracil-based systemic chemotherapy. After removing genera with <1% of the total reads in each patient, 523 genera were identified. Rectal origin, high CEA level (≥10 ng/mL), and presence of lung metastasis showed higher richness. Survival analysis revealed that the presence of Prevotella (p = 0.052), Fusobacterium (p = 0.002), Selenomonas (p<0.001), Fretibacterium (p = 0.001), Porphyromonas (p = 0.007), Peptostreptococcus (p = 0.002), and Leptotrichia (p = 0.003) were associated with short overall survival (OS, <24 months), while the presence of Sphingomonas was associated with long OS (p = 0.070). From the multivariate analysis, the presence of Selenomonas (hazard ratio [HR], 6.35; 95% confidence interval [CI], 2.38-16.97; p<0.001) was associated with poor prognosis along with high CEA level. Tumor microbiome features may be useful prognostic biomarkers for metastatic CRC.

Expression of Immune-Related and Inflammatory Markers and Their Prognostic Impact in Colorectal Cancer Patients.

The tumor microenvironment of colorectal cancer (CRC) is heterogenous; thus, it is likely that multiple immune-related and inflammatory markers are simultaneously expressed in the tumor. The aim of this study was to identify immune-related and inflammatory markers expressed in freshly frozen CRC tissues and to investigate whether they are related to the clinicopathological features and prognosis of CRC. Seventy patients with CRC who underwent curative surgical resection between December 2014 and January 2017 were included in this study. Tissue samples were obtained from tumor and non-tumor areas in the patients' colons. The concentrations of immune-related markers (APRIL/TNFSF13, BAFF, LAG-3, PD-1, PD-L1, and CTLA-4) and inflammatory markers (CHIT, MMP-3, osteocalcin, pentraxin-3, sTNF-R1, and sTNF-R2) in the samples were measured using the Bio-plex Multiplex Immunoassay system. The concentrations of APRIL/TNFSF13, BAFF, and MMP-3 in the samples were significantly high; thus, we conducted analyses based on the cut-off values for these three markers. The high-APRIL/TNFSH13-expression group showed a significantly higher rate of metastatic lesions than the low-expression group, whereas the high-MMP-3-expression group had higher CEA levels, more lymph node metastases, and more advanced disease stages than the low-expression group. The five-year disease-free survival of the high-MMP-3-expression group was significantly shorter than that of the low-expression group (65.1% vs. 90.2%, p = 0.033). This study provides evidence that the APRIL/TNFSF13, BAFF, and MMP-3 pathway is overexpressed in CRC tissues and is associated with unfavorable clinicopathological features and poor prognosis in CRC patients. These markers could serve as diagnostic or prognostic biomarkers for CRC.

High preoperative CEA and systemic inflammation response index (C-SIRI) predict unfavorable survival of resectable colorectal cancer

BackgroundCEA and systemic inflammation were reported to correlate with proliferation, invasion, and metastasis of colorectal cancer. This study investigated the prognostic significance of the preoperative CEA and systemic inflammation response index (C-SIRI) in patients with resectable colorectal cancer.MethodsTwo hundred seventeen CRC patients were recruited from Chongqing Medical University, the first affiliated hospital, between January 2015 and December 2017. Baseline characteristics, preoperative CEA level, and peripheral monocyte, neutrophil, and lymphocyte counts were retrospectively reviewed. The optimal cutoff value for SIRI was defined as 1.1, and for CEA, the best cutoff values were 4.1 ng/l and 13.0 ng/l. Patients with low levels of CEA (< 4.1 ng/l) and SIRI (< 1.1) were assigned a value of 0, those with high levels of CEA (≥ 13.0 ng/l) and SIRI (≥ 1.1) were assigned a value of 3, and those with CEA (4.1–13.0 ng/l) and SIRI (≥ 1.1), CEA (≥ 13.0 ng/l), and SIRI (< 1.1) were assigned a value of 2. Those with CEA (< 4.1 ng/l) and SIRI (≥ 1.1) and CEA (4.1–13.0 ng/l) and SIRI (< 1.1) were assigned a value of 1. The prognostic value was assessed based on univariate and multivariate survival analysis.ResultsPreoperative C-SIRI was statistically correlated with gender, site, stage, CEA, OPNI, NLR, PLR, and MLR. However, no difference was observed between C-SIRI and age, BMI, family history of cancer, adjuvant therapy, and AGR groups. Among these indicators, the correlation between PLR and NLR is the strongest. In addition, high preoperative C-SIRI was significantly correlated with poorer overall survival (OS) (HR: 2.782, 95% CI: 1.630–4.746, P < 0.001) based on univariate survival analysis. Moreover, it remained an independent predictor for OS (HR: 2.563, 95% CI: 1.419–4.628, p = 0.002) in multivariate Cox regression analysis.ConclusionOur study showed that preoperative C-SIRI could serve as a significant prognostic biomarker in patients with resectable colorectal cancer.

Targeted Therapy in the Palliative Setting of Colorectal Cancer-Survival and Medical Costs.

(1) Background: Targeted therapy is used alone or together with chemotherapy in metastatic colorectal cancer. The aim of this study was to assess overall survival and medical costs in a cohort of patients with metastatic colorectal cancer. (2) Methods: Demographic and clinical characteristics of 337 patients and pathological data of colorectal tumors were retrospectively collected in this population-based study. The overall survival and medical costs for patients receiving chemotherapy plus targeted therapy were compared with those for patients receiving chemotherapy only. (3) Results: Patients administered chemotherapy plus targeted therapy were less frail and had more often RAS wild-type tumors but had higher CEA levels than patients receiving chemotherapy only. No prolonged overall survival could be observed in patients receiving palliative targeted therapy. The medical costs for patients undergoing treatment with targeted therapy were significantly higher than for patients treated only with chemotherapy; they were especially higher in the group receiving targeted therapy early than late in the palliative setting. (4) Conclusions: The use of targeted therapy in metastatic colorectal cancer leads to significantly higher medical costs when used early in the palliative setting. No positive effects of the use of targeted therapy could be observed in this study; therefore, we suggest that targeted therapy be used in later lines of palliative therapy in metastatic colorectal cancer.

Laparoscopic posterior pelvic exenteration is safe and feasible for locally advanced primary rectal cancer in female patients: a comparative study from China PelvEx collaborative.

Posterior pelvic exenteration (PPE) for locally advanced rectal cancer is a technical and challenging procedure. The safety and feasibility of laparoscopic PPE remain to be determined. This study aims to compare short-term and survival outcomes of laparoscopic PPE (LPPE) with open PPE (OPPE) in female patients. From January 2015 to December 2020, data from 105 female patients who underwent PPE at three institutions were retrospectively analyzed. The short-term and oncological outcomes between LPPE and OPPE were compared. A total of 54 cases with LPPE and 51 cases with OPPE were enrolled. The operative time (240 vs. 295min, p = 0.009), blood loss (100 vs. 300ml, p < 0.001), surgical site infection (SSI) rate (20.4% vs. 58.8%, p = 0.003), urinary retention rate (3.7% vs. 17.6%, p = 0.020), and postoperative hospital stay (10 vs. 13days, p = 0.009) were significantly lower in the LPPE group. The two groups showed no significant differences in the local recurrence rate (p = 0.296), 3-year overall survival (p = 0.129), or 3-year disease-free survival (p = 0.082). A higher CEA level (HR1.02, p = 0.002), poor tumor differentiation (HR3.05, p = 0.004), and (y)pT4b stage (HR2.35, p = 0.035) were independent risk factors for disease-free survival. LPPE is safe and feasible for locally advanced rectal cancers and shows lower operative time and blood loss, fewer SSI complications, and better preservation of bladder function without compromising oncological outcomes.

Predictive Value of Serum Heat Shock Protein 90α on the Prognosis of Patients with Lung Adenocarcinoma.

Heat shock protein 90α (HSP90α) is highly expressed in tumors, and predicts tumor progression. This study analyzed the correlation between the expression level of HSP90α in the serum and the prognosis of patients with lung adenocarcinoma. The medical records of patients with 228 lung adenocarcinoma from September 2015 to December 2021 were analyzed. HSP90α expression in the patients' serum was detected by ELISA and the cut-off value (93.76 ng/mL) was determined according to the ROC curve, then the patients were divided into high- and low-level groups. The differences in the medical records of the two groups were compared using the X2 test, and Univariate and multivariate Cox regression analyses showed that serum HSP90α level were independent risk factors for both PFS and OS (P < 0.05). HSP90α was positively correlated with TNM staging (P < 0.01) by One-way analysis of variance. The results of the correlation analysis and the Kaplan-Meier survival curve showed that the expression levels of HSP90α and CEA of patients were positively correlated (R=0.54, P < 0.001), and patients with high HSP90α and CEA levels had the worst OS (P < 0.001). HSP90α expression is negatively correlated with the prognosis of patients with lung adenocarcinoma and is a potential prognostic marker.

Predicting Limited Survival After Resection of Synchronous Colorectal Liver Metastases: a Propensity Score Matched Comparison Between The Primary First And The Simultaneous Strategy

BackgroundThe best surgical approach to treat synchronous colorectal liver metastases (CRLM) remains unclear. Here, we aimed to identify prognostic factors associated with limited survival comparing patients undergoing primary-first resection (PF) and simultaneous resection (SR) approaches. MethodsWe retrospectively reviewed clinical data of 217 patients who underwent resection for synchronous CRLMs between January 1, 2011, and December 31, 2021. There were 133 (61.2%) PF resection and 84 (38.8%) SRS. The two groups of patients were compared using propensity score matching (PSM) analysis and cox analysis was performed to identify prognostic factors for overall survival (OS). ResultsAfter PSM, two groups of 71 patients were compared. Patients undergoing SR had longer operative time (324 ± 104 min vs 250 ± 101 min; p < 0.0001), similar transfusion (33.3% vs 28.1%; p = 0.57), and similar complication rates (35.9% vs 27.2%; p = 0.34) than patients undergoing PF. The median overall survival and 5-year survival rates were comparable (p = 0.94) between patients undergoing PF (48.2 months and 44%) and patients undergoing SR (45.9 months and 30%). Multivariate Cox analysis identified pre-resection elevated CEA levels (HR: 2.38; 95% CI: 1.20–4.70; P = .01), left colonic tumors (HR: 0.34; 95% CI: 0.17–0.68; P = .002), and adjuvant treatment (HR: 0.43; 95% CI: 0.22–0.83; P = .01) as independent prognostic factors for OS. ConclusionsIn the presence of synchronous CRLM, right colonic tumors, persistent high CEA levels before surgery, and the absence of adjuvant treatment identified patients characterized by a limited survival rate after resection. The approach used (PF vs SR) does not influence short and long-term outcomes.

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.

Clinicopathological Features and Significance of Epidermal Growth Factor Receptor Mutation in Surgically Resected Early-Stage Lung Adenocarcinoma.

The clinicopathological presentation of early-stage lung adenocarcinoma patients with epidermal growth factor receptor (EGFR) mutations has been seldom studied. Our study enrolled patients with stage I and II lung adenocarcinoma between January 2014 and December 2017 at the National Taiwan University Hospital. Clinicopathological features and prognosis were retrospectively reviewed and analyzed depending on EGFR mutation status. EGFR mutations were detected in 622 (60%) out of 1034 patients. Compared to the group without EGFR mutations, the group with EGFR mutations had more patients above 65 years of age (p < 0.001), more non-lepidic histological subtypes (p < 0.001), higher CEA levels (p = 0.044), higher grade of pleural (p = 0.02) and lymphovascular (p = 0.001) invasion, higher histological grade (p < 0.001), and a more advanced pathological stage (p = 0.022). In multivariate analysis, there was no significant difference in PFS or OS between the EGFR mutant and wild-type groups. In subtype analysis, the tumors with an L858R mutation had a more lepidic predominant histological type (p = 0.019) and less lymphovascular invasion (p = 0.011). No significant differences in PFS or OS were detected between the exon 19 deletion and L858R mutation groups. In early-stage lung adenocarcinoma, EGFR mutation may be considered as a treatment response predictor for tyrosine kinase inhibitors, instead of a predictor of clinical prognosis.

Preoperative diagnosis of perineural invasion in patients with periampullary carcinoma by MSCT imaging: preliminary observations and clinical implications.

The aim of this study was to investigate the value of multi-slice computed tomography (MSCT) in preoperatively diagnosing perineural invasion (PNI) of periampullary carcinoma (PAC). Of 81 patients pathologically diagnosed as PAC, 73 patients were included. Their clinical documents and preoperative upper abdominal enhanced MSCT images were retrospectively reviewed to analyse clinical characteristics and MSCT features. MSCT features included tumor size, classification of fat tissue around celiac trunk and superior mesenteric artery. Chi-square test, Mann-Whitney U test or Fisher's exact test were used to compare the differences between PNI group and Non-PNI group. ROC analysis was performed to evaluate diagnostic efficiency for PAC PNI. There were significant differences in some clinical characteristics and MSCT features. PAC PNI patients had significantly higher CA19-9 levels, higher CEA levels, larger tumor size and higher classification of fat tissue around celiac trunk than Non-PNI patients (All P values < 0.05). In univariate analysis, tumor size had the highest AUC as 0.806, fat tissue around celiac trunk and CEA had the highest specificity as 100% (P < 0.001). In multivariate analysis, classification of fat tissue around celiac trunk incorporated with tumor size, CA19-9, CEA, age and sex, showed the highest AUC as 0.939, with specificity of 95.0% and sensitivity of 90.4% (P < 0.001). PAC PNI could be diagnosed preoperatively by evaluating abdominal enhanced MSCT images with high accuracy, combined with serum tumor marker could be more helpful.

Actual over 3-year survival after stereotactic body radiation therapy in patients with unresectable intrahepatic cholangiocarcinoma.

As a non-invasive treatment, stereotactic body radiation therapy (SBRT) has been an emerging and effective option for patients with unresectable intrahepatic cholangiocarcinoma (ICC). The Cyber Knife has an SBRT system, which can realize real-time tracking of tumors during treatment. It can protect the surrounding normal liver tissue while the tumor gets the therapeutic dose. The purpose of this study was to evaluate the factors affecting the local control rate for patients after SBRT treatment, and to predict the factors affecting survival rates, then to report the 3-year actual survival rates after treatment and identify the influencing factors of 3-year survival rate. We conducted a long-term follow-up of 43 patients with unresectable intrahepatic cholangiocarcinoma who underwent Cyber Knife in our hospital from January 2016 to December 2018. Regular medical check-ups were performed every 2-3 months after SBRT to evaluated the effect of treatment. The median follow-up time was 15 months (4-78 months), and the median progression-free survival (PFS) was 6 months (95% CI, 2.788-9.212) and the median overall survival (OS) was 12 months (95% CI, 3.434-20.566), respectively. Based on modified Response Evaluation and Criteria in Solid Tumor (mRECIST), response rate (RR) and disease control rate (DCR) of SBRT in unresectable ICC were 55.2% and 86%. The 1-, 2- and 3-years OS rate were 51.2%, 32.6% and 23.3%. Multivariate analysis based on competing risk survival analysis identified that patients with multiple nodules, large diameter, high level of CA199 and CEA, poor ECOG performance status had worse overall survival (p<0.05). Patients who survived ≥3 years had significantly lower levels of CEA, CA199, smaller tumor diameters and lower number of lesions (p<0.05). The SBRT might be a candidate option for patients who unable to perform surgery. The rate of 3-year survival after SBRT for unresectable ICC can be expected with 23.3%.

Neutrophil-albumin ratio as a biomarker for postoperative complications and long-term prognosis in patients with colorectal cancer undergoing surgical treatment.

To explore the prognostic value of the preoperative neutrophil-albumin ratio (NAR) in patients with colorectal cancer (CRC) undergoing surgical treatment. The standardized log-rank statistic was used to determine the optimal cut-off value for NAR. A logistic regression model was used to evaluate the value of NAR in predicting postoperative complications. Cox proportional hazards models were used to assess the independent association of NAR with progression-free survival (PFS) and overall survival (OS) in CRC patients. Restricted cubic splines were used to assess the relationship between continuous NAR and survival in CRC patients. The Kaplan-Meier method and log-rank test were used to compare survival differences between low and high NAR groups. NAR-based prognostic nomograms were constructed to predict the 1-5-year PFS and OS of CRC patients. The concordance index (C-index) and calibration curve were used to evaluate the prognostic accuracy of the nomograms. A total of 1,441 CRC patients were enrolled from January 2012 to December 2016. There were 904 men (62.7%) and 537 women (37.3%), with an average age of 58.12 ± 13.15 years. High NAR was closely associated with low BMI, advanced pathological stage, colon cancer, large tumors, vascular invasion, poor differentiation, high CEA levels, long hospital stay, and recurrence and metastasis. A high NAR was an independent risk factor for postoperative complications in CRC patients (OR: 2.298, 95% CI: 1.642-3.216, p < 0.001). Patients with a high NAR had worse PFS (40.7 vs. 59.5%, p < 0.001) and OS (42.6 vs. 62.4%, p < 0.001). After adjusting for confounders, high NAR was independently associated with PFS (HR: 1.280, 95% CI: 1.031-1.589, p = 0.025) and OS (HR: 1.280; 95% CI: 1.026-1.596, p = 0.029) in CRC patients. The C-index and calibration curves showed that the NAR-based prognostic nomograms had good predictive accuracy. High NAR was an independent risk factor for postoperative complications and long-term prognosis of CRC patients. NAR-based research could provide references for prognostic judgment and clinical decision-making of CRC patients.

Recursive Partitioning Model to Identify Early Progression in Patients with Extracranial Oligometastatic Colorectal Cancer Treated with Stereotactic Body Radiotherapy

<h3>Purpose/Objective(s)</h3> Metastases directed therapy of oligometastatic colorectal cancer (CRC) may confer long-term disease advantages. However, there is a paucity of data to predict optimal patient selection. Our hypothesis is that pretreatment factors can identify patients at higher risk of early progression after SBRT for CRC oligometastases. <h3>Materials/Methods</h3> An institutional cohort was reviewed to identify patients with extracranial oligometastatic (≤ 5 metastases) colorectal cancer who received SBRT to all metastases. Outcomes of interest were local failure (LF), overall survival (OS) and progression-free survival (PFS). Recursive partitioning analysis (RPA) was performed to identify "early progression", defined as those having a PFS event within 6 months of SBRT, from a training set consisting of 70% of the cohort. The remaining 30% were used in the validation analysis of the model. <h3>Results</h3> From January 2008 to May 2021, 254 patients were identified with 408 lesions irradiated. Median age was 75 years (IQR: 62-82), median follow-up was 30.5 months (IQR: 17.7-48.8), and median time from diagnosis of cancer to metastatic disease was 12.0 months (IQR: 0.2-26.1). The majority of patients had a single metastasis (n=167, 65.8%). The 12-, 24- and 36-month cumulative incidence of LF was 10.3%, 22.8% and 27.5%, respectively. On multivariable analysis (MVA), liver metastasis (vs. non-liver, HR 1.99, 95%CI: 1.32-3.00, p<0.01) and lower mean PTV dose BED₁₀ (HR: 1.01, 95%CI: 1.01-1.02, p<0.01) predicted for higher LF. Median OS was 51.1 months (95%CI: 46.2-56.3) and 12-, 24- and 36-month OS was 94.0%, 79.5% and 64.9%, respectively. On MVA, higher pre-SBRT CEA (HR: 1.21, 95%CI: 1.01-1.45, p=0.04) and larger PTV volume (HR: 1.61, 95%CI: 1.31-1.97, p<0.01) were significant predictors of worse OS. Median PFS was 11.8 months (95%CI: 9.9-13.7) and 6-, 12- and 24-month PFS was 73.2%, 49.2% and 30.4%, respectively. Of the 254 patients included, 68 (26.8%) had "early progression". The RPA model ranked the following variables in order of importance: presence or history of any liver metastases, pre-SBRT CEA and number of lesions treated at time of SBRT. Four terminal nodes (i.e., groups) were generated, classifying the probability of "early progression" with a training and validation receiver operating characteristic curve (AUC) of 0.72 and 0.71, respectively. The two groups at highest risk of early progression were: 1) history or presence of any liver metastases and with ≥2 lesions treated; and 2) history or presence of any liver metastases with 1 lesion treated at the time of SBRT, and pre-SBRT CEA ≥8 ng/mL. <h3>Conclusion</h3> History or presence of liver metastases, higher number of lesions, and higher CEA levels can aid in the identification of oligometastatic patients who progress soon after SBRT. Such patients can be considered for alternative treatment strategies.

Metabolic tumor volume predicts long-term survival after transplantation for unresectable colorectal liver metastases: 15 years of experience from the SECA study

ObjectiveTo report 15 years of experience with metabolic tumor volume (MTV) of liver metastases from the preoperative 18F-FDG PET/CT to predict long-term survival after liver transplantation (LT) for unresectable colorectal liver metastases (CRLM).MethodsThe preoperative 18F-FDG PET/CT from all SECA 1 and 2 patients was evaluated. MTV was obtained from all liver metastases. The patients were divided into one group with low MTV (< 70 cm3) and one group with high MTV (> 70 cm3) based on a receiver operating characteristic analysis. Overall survival (OS), disease-free survival (DFS) and post recurrence survival (PRS) for patients with low versus high MTV were compared using the Kaplan–Meier method and log rank test. Clinopathological features between the two groups were compared by a nonparametric Mann–Whitney U test for continuous and Fishers exact test for categorical data.ResultsAt total of 40 patients were included. Patients with low MTV had significantly longer OS (p < 0.001), DFS (p < 0.001) and PRS (p = 0.006) compared to patients with high values. The patients with high MTV had higher CEA levels, number of liver metastases, size of the largest liver metastasis, N-stage, number of chemotherapy lines and more frequently progression of disease at LT compared to the patients with low MTV.ConclusionMTV of liver metastases is highly predictive of long-term OS, DFS and PRS after LT for unresectable CRLM and should be implemented in risk stratification prior to LT.