Baseline Carcinoembryonic Antigen Research Articles

Prognostic factors for survival in NSCLC treated with immunotherapy: An institutional analysis.

e20591 Background: Immune check point inhibitors (ICIs) are the cornerstone of treatment for patients with advanced NSCLC. However, not all patients benefit from ICIs and some develop significant immune-mediated toxicities. There is limited data regarding prognostic factors in NSCLC patients treated with ICIs. Imaging features can complement clinical variables in predicting response to ICIs. This study aims to evaluate CEA, blood leukocyte markers, and novel CT-derived radiomic features as factors predictive of survival in this patient population. Methods: In this retrospective study, clinical data from patients with advanced stage NSCLC treated with ICIs at Stony Brook University Hospital from 2016 to 2021 were collected. Baseline and subsequent CEA (carcinoembryonic antigen), ANC (absolute neutrophil count), ALC (absolute lymphocyte count), NLR (neutrophil to lymphocyte ratio), AEC (absolute eosinophil count), and AMC (absolute monocyte count) were evaluated as independent prognostic factors. 3-D segmentation of ipsilateral lung lobe was obtained using U-Net and radiologist report of tumor location. 600 stable IBSI-standardized features were extracted from the region using PyRadiomics. The discriminative ability of clinical and image-derived variables was assessed using Kaplan-Meier survival and Cox proportional hazards regression analysis. Results: This study included 80 patients. Objective response rate (ORR) was 25.0% with 1-year OS of 58.0%. PD-L1 expression ≥ 50% was significantly associated with survival (p < 0.02). Decrease in CEA (p < 0.01) and 5% increase in AEC (p = 0.027) significantly correlated with survival. Age, sex, clinical stage, ANC, ALC, NLR, AMC did not significantly predict survival. Three image biomarkers that correlated with median enhancement of tissue on chest CT, and degree of tissue heterogeneity were significant predictors of mortality (p < 0.02). A multivariable model with clinical inputs outperformed one with radiomic features only (C-index 0.70 vs. 0.64). Clinical and radiomic inputs together performed well in predicting survival (C-index 0.76). Conclusions: Changes in CEA and AEC were the strongest predictors of survival in advanced NSCLC patients treated with ICIs. This study suggests that combined clinical and radiomic biomarkers (quantifying local lobar heterogeneity) can identify patients most likely to benefit from immunotherapy. [Table: see text]

Risk of advanced neoplasia after removal of colorectal adenomas with high-grade dysplasia

BackgroundMany studies reported the presence of adenomas with high-grade dysplasia (HGD) at index colonoscopy increased the incidence of advanced neoplasia (AN) and colorectal cancer (CRC) following. However, the conclusion remains obscure due to lack of studies on the specific population of adenomas with HGD. This study aimed to assess the long-term risk of AN and CRC after removal of adenomas with HGD.MethodsA total of 814 patients who underwent adenomas with HGD removal between 2010 and 2019 were retrospectively analyzed. The outcomes were the incidences of AN and CRC during surveillance colonoscopy. Cox proportional hazards models were utilized to identify risk factors associated with AN and CRC.ResultsDuring more than 2000 person-years of follow-up, we found that AN and CRC incidence densities were 44.3 and 4.4 per 1000 person-years, respectively. The 10-year cumulative incidence of AN and CRC were 39.1% and 5.5%, respectively. In the multivariate model, synchronous low-risk polyps (HR 1.80, 95% CI 1.10–2.93) and synchronous high-risk polyps (HR 3.99, 95% CI 2.37–6.72) were risk factors for AN, whereas participation in surveillance colonoscopy visits (HR 0.56, 95% CI 0.36–0.88 for 1 visit; HR 0.10, 95% CI 0.06–0.19 for ≥ 2 visits) were associated with decreased AN incidence. Additionally, elevated baseline carcinoembryonic antigen (CEA) level (HR 10.19, 95% CI 1.77–58.59) was a risk factor for CRC, while participation in ≥ 2 surveillance colonoscopy visits (HR 0.11, 95% CI 0.02–0.56) were associated with decreased CRC incidence. Interestingly, for 11 patients who developed CRC after removal of adenomas with HGD, immunohistochemistry revealed that 8 cases (73%) were deficient mismatch repair CRCs.ConclusionsPatients who have undergone adenoma with HGD removal are at higher risk of developing AN and CRC, while surveillance colonoscopy can reduce the risk. Patients with synchronous polyps, or with elevated baseline CEA level are considered high-risk populations and require more frequent surveillance.

Abstract 6408: Early carcinoembryonic antigen (CEA) dynamics to predict the efficacy of fruquintinib (F) + best supportive care (BSC) in patients with metastatic colorectal cancer (mCRC) enrolled in FRESCO-2

Abstract Background: The phase 3 FRESCO-2 trial (NCT04322539) demonstrated a significant survival benefit with fruquintinib (F) + BSC vs placebo (P) + BSC as third or later line of therapy for patients (pts) with mCRC. Based on the results of FRESCO-2, F was FDA-approved for adults with previously treated mCRC, irrespective of biomarker status. In mCRC, CEA levels and imaging are routinely used to monitor response to systemic therapy. We investigated early CEA changes during treatment in FRESCO-2 and possible relationships with efficacy. Methods: Pts with abnormal baseline (BL) CEA were included based on local lab reference ranges. Serum CEA levels were measured at BL and Day 1 (D1) of each 28-day cycle (C) except C1. Changes in CEA levels were analyzed at C2D1 and C3D1. CEA response was defined as ≥50% decrease from BL, and CEA progression was defined as ≥100% increase from BL. Tumor evaluation was performed by CT or MRI scan every 2 cycles. Overall survival (OS) and progression-free survival (PFS) were evaluated by Kaplan-Meier method; hazard ratio (HR) was estimated via Cox proportional hazards model; p-value was generated from log rank test. Results: Overall, 88.3% (407/461) vs 90.4% (208/230) of pts had abnormal BL CEA in F vs P arms; median BL CEA values were similar between treatment arms (Table). At C3D1, the proportion of pts who had a CEA response was significantly higher with F vs P (35.5% vs 3.8%, P <0.001) and the proportion who had CEA progression was significantly lower (5.7% vs 47.2%, P <0.001). Pts in the F arm with CEA response at C3D1 had improved OS and PFS vs pts without CEA response and pts with CEA progression (Table). These results were consistent for pts who had an early CEA response at C2D1 (Table). Conclusion: CEA response at C2D1 and C3D1 could be considered an early predictor for improved OS and PFS. Pts with CEA response seem to benefit from F + BSC compared with pts without response or with CEA progression. Table. CEA changes from baseline in pts in the F + BSC vs P + BSC arms, and OS and PFS based on CEA response in pts in the F + BSC arm CEA changes from baseline by treatment arm (ITT population) F + BSC (N=461) P + BSC (N=230) Baseline, n 407 208 Median CEA (range), µg/L 132.4 (3.0-213000.0) 169.6 (3.2-90010.0) C2D1, n 340 151 Median CEA (range), µg/L 93.3 (2.0-98660.0) 133.5 (2.7-255910.0) Median change from baseline (range), % -19.2 (-90.5-467.8) 44.2 (-61.7-606.8) C3D1, n 245 53 Median CEA (range), µg/L 78.3 (1.7-133390.0) 145.2 (3.9-17782.0) Median change from baseline (range), % -31.0 (-91.4-2195.8) 90.5 (-68.9-3776.6) OS and PFS for pts in the F + BSC arm with or without CEA response at C2D1 and C3D1 Pts with early CEA response at C2D1(n=66) Pts without early CEA response at C2D1 (n=274) Pts with CEA response at C3D1 (n=87) Pts without CEA response at C3D1 (n=158) Median OS, months 10.0 7.4 11.1 8.5 HR (95% CI), P value 0.62 (0.44-0.89), P = 0.009 0.65 (0.46-0.92), P = 0.015 Median PFS, months 5.6 3.7 5.8 4.2 HR (95% CI), P value 0.68 (0.51-0.92), P = 0.01 0.58 (0.44-0.78), P = 0.0003 OS and PFS for pts in the F + BSC arm with CEA response or CEA progression at C2D1 and C3D1 Pts with early CEA response at C2D1(n=66) Pts with early CEA progression at C2D1 (n=15) Pts with CEA response at C3D1 (n=87) Pts with CEA progression at C3D1 (n=14) Median OS, months 10.0 4.3 11.1 5.6 HR (95% CI), P value 0.27 (0.14-0.51), P <0.0001 0.23 (0.12-0.45), P <0.0001 Median PFS, months 5.6 1.9 5.8 3.4 HR (95% CI), P value 0.30 (0.16-0.56), P <0.0001 0.25 (0.13-0.48), P <0.0001 Citation Format: Sara Lonardi, Arvind Dasari, Rocio Garcia-Carbonero, Takayuki Yoshino, Pilar García-Alfonso, Judit Kocsis, Chiara Cremolini, François Ghiringhelli, Ardaman Shergill, Howard S Hochster, Michel Ducreux, Dirk Arnold, Varsha Sundaresan, Siddha Kasar, Adela Pina, Ziji Yu, William R Schelman, Lucy Chen, Josep Tabernero. Early carcinoembryonic antigen (CEA) dynamics to predict the efficacy of fruquintinib (F) + best supportive care (BSC) in patients with metastatic colorectal cancer (mCRC) enrolled in FRESCO-2 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6408.

Clinical and genetic factors associated with tumor response to neoadjuvant (chemo)radiotherapy, survival and recurrence risk in rectal cancer.

Rectal cancer poses challenges in preoperative treatment response, with up to 30% achieving a complete response (CR). Personalized treatment relies on accurate identification of responders at diagnosis. This study aimed to unravel CR determinants, overall survival (OS), and time to recurrence (TTR) using clinical and targeted sequencing data. Analyzing 402 patients undergoing preoperative treatment, tumor stage, size, and treatment emerged as robust response predictors. CR rates were higher in smaller, early-stage, and intensively treated tumors. Targeted sequencing analyzed 216 cases, while 120 patients provided hotspot mutation data. KRAS mutation dramatically reduced CR odds by over 50% (odds ratio [OR] = 0.3 in the targeted sequencing and OR = 0.4 hotspot cohorts, respectively). In contrast, SMAD4 and SYNE1 mutations were associated with higher CR rates (OR = 6.0 and 6.8, respectively). Favorable OS was linked to younger age, CR, and low baseline carcinoembryonic antigen levels. Notably, CR and an APC mutation increased TTR, while a BRAF mutation negatively affected TTR. Beyond tumor burden, SMAD4 and SYNE1 mutations significantly influenced CR. KRAS mutations independently correlated with radiotherapy resistance, and BRAF mutations heightened recurrence risk. Intriguingly, non-responding tumors with initially small sizes carried a higher risk of recurrence. The findings, even if limited in addition to the imperfect clinical factors, offer insights into rectal cancer treatment response, guiding personalized therapeutic strategies. By uncovering factors impacting CR, OS, and TTR, this study underscores the importance of tailored approaches for rectal cancer patients. These findings, based on extensive analysis and mutation data, pave the way for personalized interventions, optimizing outcomes in the challenges of rectal cancer preoperative treatment.

Role of CYFRA 21-1 and CEA as prognostic and predictive markers in locally advanced and metastatic gastric carcinoma.

Tumor-associated serum markers have demonstrated predictive and prognostic value in patients being treated for malignancies. However, the clinical importance of tumor markers in gastric cancers (GC) is poorly standardized. The objective is to assess the clinical utility of cytokeratin-19 fragment (CYFRA 21-1) and carcinoembryonic antigen (CEA) as serum tumor markers in advanced GC. In this prospective study, CYFRA 21-1 and CEA levels were measured at baseline and after three cycles of chemotherapy in patients with advanced GC. The association of tumor marker levels with prognosis and decline of tumor markers with radiological overall response rates (ORR) and survival were analyzed. In the 105 patients, the proportion of patients with elevated baseline CYFRA 21-1 and CEA levels was 55% (N = 58) and 37% (N = 39) based on predefined cutoffs. Response assessment was done for 61 patients who received a minimum of three cycles of chemotherapy. A 15% and 13% reduction of serum levels from baseline for CYFRA 21-1 and CEA were selected for defining "CYFRA 21-1 response" and "CEA-response," respectively. Both responses were significant predictors of radiological ORR. The median overall survival (OS) was 9.6 months in the entire cohort and 13 months for patients who received at least three cycles of chemotherapy. In multivariate analysis, baseline CEA levels and ECOG status were significant predictors of OS. In a subset analysis of patients receiving palliative chemotherapy, any of the tumor marker responses predicted improved 1-year OS. In advanced GC, CYFRA 21-1 and CEA decline from baseline appeared to be reliable surrogate markers of chemotherapy efficacy and improved survival.

Refining first-line treatment decision in RAS wildtype (RAS-WT) metastatic colorectal cancer (mCRC) by combining clinical biomarkers: Results of the randomized phase 3 trial FIRE-3 (AIO KRK0306).

13 Background: Optimal patient selection for first-line treatment targeting epithelial growth factor receptor (EGFR) in RAS-WT mCRC is based on primary tumor sidedness (PTS) with anti-EGFR being the preferred option for patients with left-sided mCRC (LC). Right-sided mCRCs (RC) are preferentially treated in combination with bevacizumab targeting vascular endothelial growth factor (VEGF). Here, improvement in patient selection was evaluated by combining clinical biomarkers beyond PTS using the randomized phase III trial FIRE-3. Methods: FIRE-3 evaluated first-line FOLFIRI (folinic acid, fluorouracil and irinotecan) plus cetuximab (FOLFIRI/Cet) versus FOLFIRI plus bevacizumab (FOLFIRI/Bev) in patients with RAS-WT mCRC. Besides PTS, further clinical biomarkers were evaluated in pairwise combinations using Cox regression models and model-based recursive partitioning with Weibull models to predict treatment benefit of either treatment arm regarding overall survival (OS): age, sex, liver-limited disease status (LLD) and baseline carcinoembryonic antigen serum level (CEA). The resulting P-values of second-order interactions were adjusted using Holm-Bonferroni correction. The model with the best test statistics and P-value was chosen for further evaluations. Results: In 400 patients with RAS-WT mCRC, a model combining PTS and LLD status best predicted treatment outcome of either treatment arm (c-index = 0.603, p=0.005). Here, a significant survival benefit of FOLFIRI/Cet over FOLFIRI/Bev was evident in patients with LC/non-LLD (HR 0.62, p=0.02) compared to LC/LLD (HR 0.83, p=0.40). In patients with RC, FOLFIRI/Bev was significantly associated with increased OS compared to FOLFIRI/Cet when patients suffered from non-LLD (HR 2.09, p=0.010). However, patients with RC/LLD rather had a benefit from FOLFIRI/Cet compared to FOLFIRI/Bev (HR 0.59, p=0.218). Conclusions: Combining clinical biomarkers PTS and LLD status might improve optimal patient selection for targeted first-line treatment in RAS-WT mCRC. Validation in further data sets is warranted. Clinical trial information: NCT00433927 .

Metastatik kolorektal kanserde regorafenib tedavi sonuçlarını etkileyen prognostik faktörler

Aim: We aimed to determine the efficacy and prognostic factors of Regorafenib in advanced colorectal cancer patients. Materials and Methods: This study was designed as single-center and retrospective. The study included 72 patients with metastatic colorectal cancer treated with Regorafenib. Univariate and multivariate analyses of factors affecting survival were generated by Cox Regression Models. Results: Twenty-three (31.9%) of the patients were female, the median age was 65 years. The median progression-free survival (PFS) and overall survival (OS) were 4.13 and 8.7 months, respectively. The carcinoembryonic antigen (CEA) level (p=0.001), and Eastern Cooperative Oncology Group (ECOG) score (p<0.001) were found to be prognostic in the multivariate model for PFS. ECOG (p<0.001), CEA level (p<0.001), dose reduction (p=0.003), and side of the primary tumor (p=0.037) were prognostic for OS. Conclusion: Our study revealed that ECOG, requiring dose reduction during the treatment, and lower baseline CEA levels were found to be prognostic.

A Real-World Retrospective Study to Evaluate the Reliability of Cetuximab plus Capecitabine versus Capecitabine as Maintenance Therapy in Patients with RAS and BRAF Wild-Type Metastatic Colorectal Cancer

Background: The optimal maintenance therapy for rat sarcoma (RAS) and v-raf murine sarcoma viral oncogene homolog B (BRAF) metastatic colorectal cancers (mCRCs) remains unclear. It is critical to evaluate the reliability of cetuximab-capecitabine (the observation group) relative to capecitabine alone (control group). Patients and Methods: In this retrospective analysis, patients with RAS and BRAF mCRC admitted to Huizhou Municipal Central Hospital, between January 2016 and October 2020 were enrolled and treated with cetuximab plus 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) as an initial therapy. Patients whose disease was controlled after at least six cycles of treatment were administered a maintenance therapy until disease progression. We also analyzed the prognosis of patients according to clinicopathological features. Altogether, 39 RAS and BRAF mCRC patients were recruited from January 2016 to October 2020, with 18 cases in the treatment group and 21 cases in the control group. The difference in baseline clinicopathological features between the two treatments is not obvious. Results: The median progression-free survival after maintenance treatment in observation group (9.5 months [95% confidence interval (CI) = 6.4–12.6]), was significantly better than the control group (7.3 months [95% CI = 5.8–8.8]). During maintenance treatment, there were no deaths caused by treatment-related adverse events, and the overall incidence of rash acne was different between the observation and control groups (p < 0.05). Most adverse events were mild and easily controlled. Primary tumor site, baseline carcinoembryonic antigen levels, and microsatellite instability status were independent prognostic factors. Conclusion: Maintenance therapy using cetuximab plus capecitabine improved survival in patients with mCRC and was well tolerated by patients.

Outcomes of laparoscopic single-incision caecal pole resection for low-grade appendiceal mucinous neoplasm.

Low-grade appendiceal mucinous neoplasm (LAMN) is a rare disease, and its clinical course varies from an incidental finding without symptoms to pseudomyxoma peritonei. Furthermore, there are few established treatment guidelines. This study was designed to confirm the outcomes in patients diagnosed with LAMN who underwent single-incision laparoscopic caecal pole resection. This study was conducted on pathologically confirmed LAMNs from patients who underwent surgery at a single centre, a tertiary institution, from July 2016 to August 2022. Patients diagnosed with LAMN as a result of biopsy were included. All surgeries were performed with single-incision laparoscopic caecal pole resection by a single surgeon. A total of 70 patients were included. The median age was 65.5 years and 36 (51.4%) patients were female. The baseline carcinoembryonic antigen (CEA) was 8.08 ng/mL (0.76-148.11). The mean maximum diameter was 29.4 mm (7-70) and calcification was seen in 22 cases on pre-operative computed tomography (CT). As a result of histological examination, all patients were marginally negative. The larger the tumour size, the higher the CEA was (P = 0.011), and it was often accompanied by calcification (P = 0.021). In addition, tumour size and CEA showed a positive partial correlation with each other (r = 0.318, P = 0.018). The overall median follow-up period was 22.7 months (2-60). One case had suspected of recurrence on CT scan performed at 33 months following the surgery, but there were no related symptoms. Single-port laparoscopic caecal pole resection without margin involvement in LAMN was safe and feasible, and showed a favourable long-term outcome.

MRI-based Radiomics Model for Preoperative Prediction of Lateral Pelvic Lymph Node Metastasis in Locally Advanced Rectal Cancer

To develop a magnetic resonance imaging (MRI)-based radiomics model for preoperative prediction of lateral pelvic lymph node (LPLN) metastasis (LPLNM) in patients with locally advanced rectal cancer MATERIALS AND METHODS: We retrospectively enrolled 263 patients with rectal cancer who underwent total mesorectal excision and LPLN dissection. Radiomics features from the primary lesion and LPLNs on baseline MRI images were utilized to construct a radiomics model, and their radiomics scores were combined to develop a radiomics scoring system. A clinical prediction model was developed using logistic regression. A hybrid predicting model was created through multivariable logistic regression analysis, integrating the radiomics score with significant clinical risk factors (baseline Carcinoembryonic Antigen (CEA), clinical circumferential resection margin status, and the short axis diameter of LPLN). This hybrid model was presented with a hybrid clinical-radiomics nomogram, and its calibration, discrimination, and clinical usefulness were assessed. A total of 148 patients were included in the analysis and randomly divided into a training cohort (n=104) and an independent internal testing cohort (n=44). The hybrid clinical-radiomics model exhibited the highest discrimination, with an area under the receiver operating characteristic (AUC) of 0.843 [95% confidence interval (CI), 0.706-0.968]in the testing cohort compared to the clinical model [AUC (95% CI)=0.772 (0.589-0.856)]and radiomics model [AUC (95% CI)=0.731 (0.613-0.849)]. The hybrid prediction model also demonstrated good calibration, and decision curve analysis confirmed its clinical usefulness. This study developed a hybrid MRI-based radiomics model that incorporates a combination of radiomics score and significant clinical risk factors. The proposed model holds promise for individualized preoperative prediction of LPLNM in patients with locally advanced rectal cancer. The data presented in this study are available on request from the corresponding author.

Carcinoembryonic antigen kinetics predict response to first-line treatment in metastatic colorectal cancer: Analysis from PRODIGE 9 trial.

To examine the relationship between carcinoembryonic antigen (CEA) kinetics and prognosis in metastatic colorectal cancer (mCRC) patients receiving first-line chemotherapy in the PRODIGE9 trial. Associations between monthly CEA measurements within 6 months since baseline and progression-free survival (PFS) were evaluated using a joint-latent class-mixed model. A validation set was used to test our prognosis model. Correlations between CEA trajectories (classes) and baseline characteristics were also investigated. Three classes were identified. Class 1 had low baseline CEA with small variations. Class 2 had high baseline CEA with a rapid decrease reaching the same CEA level at 6 months as in class 1. Class 3 had high baseline CEA with a transient decrease followed by an increase to reach, at 6 months, the same CEA level as at baseline. Six-month PFS was significantly lower in class 3 than in classes 1 and 2 (57% vs. 91% and 93% respectively; p<0.01). Class 3 was significantly associated with ECOG 2 status, a high LDH level and non-resected primary tumor. Variations in CEA kinetics correlate with prognosis in patients receiving first-line chemotherapy for mCRC. We propose here a user-friendly application to classify CEA trajectory.

A prognostic baseline blood biomarker and tumor growth kinetics integrated model in paclitaxel/platinum treated advanced non-small cell lung cancer patients.

Paclitaxel/platinum chemotherapy, the backbone of standard first-line treatment of advanced non-small cell lung cancer (NSCLC), exhibits high interpatient variability in treatment response and high toxicity burden. Baseline blood biomarker concentrations and tumor size (sum of diameters) at week 8 relative to baseline (RS8) are widely investigated prognostic factors. However, joint analysis of data on demographic/clinical characteristics, blood biomarker levels, and chemotherapy exposure-driven early tumor response for improved prediction of overall survival (OS) is clinically not established. We developed a Weibull time-to-event model to predict OS, leveraging data from 365 patients receiving paclitaxel/platinum combination chemotherapyonceeverythreeweeks for ≤six cycles. A developed tumor growth inhibition model, combining linear tumor growth and first-order paclitaxel area under the concentration-time curve-induced tumor decay, was used to derive individual RS8. The median model-derived RS8 in all patients was a 20.0% tumor size reduction (rangefrom -78% to +15%). Whereas baseline carcinoembryonic antigen, cytokeratin fragments, and thyroid stimulating hormone levels were not significantly associated with OS in a subset of 221 patients, and lactate dehydrogenase, interleukin-6 and neutrophil-to-lymphocyte ratio levels were significant only in univariate analyses (p value < 0.05); C-reactive protein (CRP) in combination with RS8 most significantly affected OS (p value < 0.01). Compared to the median population OS of 11.3months, OS was 128% longer at the 5th percentile levels of both covariates and 60% shorter at their 95th percentiles levels. The combined paclitaxel exposure-driven RS8 and baseline blood CRP concentrations enables early individual prognostic predictions for different paclitaxel dosing regimens, forming the basis for treatment decision and optimizing paclitaxel/platinum-based advanced NSCLC chemotherapy.

Adjuvant chemotherapy for older patients with stage II/III gastric cancer: A retrospective cohort study.

303 Background: Current clinical guidelines recommended adjuvant chemotherapy for stage II and stage III gastric cancer after operation. The older patients were underrepresented in clinical trials and the role of adjuvant chemotherapy for older patients is unclear. We aimed to investigate the benefit of adjuvant chemotherapy in older patients with stage II and stage III gastric cancer. Methods: We retrospectively reviewed the medical records of patients with stage II-III gastric adenocarcinoma and underwent curative surgery at Taichung Veterans General Hospital (Taichung, Taiwan) between January 2009 and June 2017. The clinical characteristics and outcomes of patients ≥70-year-old were compared between patients received adjuvant chemotherapy or not received adjuvant chemotherapy. Results: A total of 357 patients were analyzed and 164 patients were older or equal to 70 years old. Majority of the young patients received adjuvant chemotherapy but only two-thirds of the old patients received adjuvant chemotherapy (93.8% vs. 61%; P&lt;0.001). Among older patients, receipt of adjuvant chemotherapy was associated with longer disease-free survival (DFS) (10-year DFS, 45.89% vs. 17.55%; P&lt;0.001) and overall survival (OS) (10-year OS, 61.71% vs. 36.27%; P=0.023) compared with patients who did not receive adjuvant chemotherapy. The total gastrectomy (hazard ratio (HR): 2.26; P=0.015), more advanced stage (HR: 2.71; P=0.018), positive surgical margin (HR: 2.56; P=0.02), elevated baseline carcinoembryonic antigen (HR: 2.37; P=0.026) were independent prognostic factors for OS in patients ≥70-year-old. Notably, the benefit adjuvant chemotherapy in older patients was significant in univariate analysis (HR: 0.53; P=0.025) but was not confirmed in multivariate analysis (HR: 0.52; P=0.072). Conclusions: The benefit of adjuvant chemotherapy in older patients with stage II-III gastric cancer was controversial in this retrospective study. Further prospective studies are needed to investigate this issue.

Total neoadjuvant treatment approach and carcinoembryonic antigen level in locally advanced rectal cancer.

e15595 Background: Total Neoadjuvant therapy (TNT) has gained acceptance in the treatment of locally advanced rectal cancer, although the optimal sequencing of therapy chemoradiation (CRT) followed by consolidation chemotherapy (cChT) or induction chemotherapy followed by chemoradiation (iChT), remains a subject of ongoing debate. The effect of TNT sequencing and carcinoembryonic antigen (CEA) level on progression free survival (PFS) is uncertain. We conducted a retrospective analysis to examine these issues. Methods: Patients (n = 44) with locally advanced rectal cancer from June 2016 to December 2020 were reviewed. CEA level was compared against the primary outcome of response to TNT approaches. We categorized patients into 3 groups based on pre-TNT and post-TNT (i.e. pre-surgical) CEA: normal CEAPRE/normal CEAPOST, elevated CEA PRE/normal CEA POST, elevated CEA PRE/elevated CEA POST. 3-Year PFS was calculated using Kaplan-Meier method. Univariable and multivariable logistic regression analyses identified characteristics predictive of PFS and clinicopathologic variables associated with TNT sequencing. Results: The study cohort had a median age of 61 years and was predominantly male (70%) and Caucasian (94%). Pre-treatment stage was either II (27%) or III (72%), with the majority (65%) undergoing iChT. Downstaging occurred in 42/44 (95%). Baseline CEA was elevated in 40.9% of patients. On multivariable, logistic regression variable associated with receipt of CRT followed by cChT included: Age &gt; 61 years clinical T4 disease and lack of T downstaging (p &lt; 0.05 for all).There was no difference in 3-year PFS between patients receiving iChT versus patients receiving cChT (p = 0.53). When patients were stratified according to pretreatment CEA level, no difference in 3 year PFS were noted (p = 0.46). On multivariable analysis, lack of nodal downstaging following neoadjuvant treatment was associated with higher likelihood of progression (p = 0.02). Similarly, pretreatment CEA &gt; 4.25 ng/ml (p = 0.08) and failure of CEA to decrease by &gt;2 ng/ml following TNT (p = 0.07) trended toward higher likelihood of progression. Conclusions: Neither TNT sequencing, nor baseline CEA predicted the PFS although the power of our study was limited. Lack of nodal downstaging was identified as a predictor of worse PFS. Further areas of study should include plasma-based assays to quantitate circulating tumor DNA and next generation sequencing to assess prognosis with different sequencing of TNT.

Efficacy and safety analysis of bevacizumab combined with capecitabine in the maintenance treatment of RAS-mutant metastatic colorectal cancer.

What is known and objectivesThe optimal strategy for maintenance therapy in patients with metastatic colorectal cancer (mCRC) remains controversial. Considering that, beyond progression, co‐therapy with bevacizumab and cytotoxic chemotherapy showed less toxicity and a significant disease control rate. We aimed to investigate the differences in efficacy and safety between bevacizumab combined with capecitabine maintenance therapy and capecitabine monotherapy for RAS‐mutant mCRC （as defined by mutations in KRAS and NRAS exons 2–4）controlled by bevacizumab plus FOLFIRI chemotherapy for at least 12 weeks.MethodsWe retrospectively analysed patients with RAS‐mutant mCRC admitted to the Department of Oncology, Huizhou Municipal Central Hospital from December, 2015 to December, 2020. All patients were first treated with bevacizumab combined with FOLFIRI for at least 12 weeks of induction therapy. 154 patients whose disease was brought under control then continued maintenance therapy. 78 patients were in the observation group (bevacizumab plus capecitabine) and 76 patients were in the control group (capecitabine alone). The efficacy and adverse effects of maintenance treatment were compared between the two groups. The clinicopathological characteristics such as sex, age, performance status (PS) score, primary tumour site, degree of pathological differentiation, baseline carcinoembryonic antigen (CEA) level, microsatellite instability (MSI) status, number of metastatic tumour sites and efficacy of induction treatment were compared in terms of prognosis.Results and discussionThe median progression‐free survival (mPFS)of patients was 9.0 months (95% CI 8.0–10.0) in the observation group and 7.2 months (95% CI 6.0–8.4) in the control group, with a statistically significant difference (p < 0.05). The baseline CEA level was an independent prognostic factor. Both groups tolerated the toxic side effects.What is new and conclusionBevacizumab combined with capecitabine was well tolerated and contributed to a longer PFS time than capecitabine alone, and it is worthy of popularization in clinical practice.

Survival outcome and treatment response of patients with young-onset locally advanced rectal cancer (YO-LARC) receiving total neoadjuvant therapy (TNT).

44 Background: Despite an alarming rise in incidence, data on survival outcome and treatment response of young-onset (age &lt; 50 years) locally advanced rectal cancer (YO-LARC) patients receiving total neoadjuvant therapy (TNT) are sparse. We retrospectively compared the outcome between YO-LARC and later-onset (aged 50 years or older) LARC (LO-LARC) patients treated with TNT. Methods: After the institutional review board approval, electronic medical records of the LARC (T3/T4 or node-positive) patients treated with TNT at a tertiary care cancer center between January 1, 2015, and June 30, 2020, were reviewed for data collection. TNT consisted of systemic chemotherapy with oxaliplatin-based regimens for 16 weeks followed by long-course radiation with concurrent capecitabine or 5-fluorouracil (CRT). Patients receiving only preoperative CRT were excluded. Most patients underwent surgical resection following the TNT. Non-operative management was offered to patients if TNT resulted in clinical complete response (cCR). The following comparisons between the YO-LARC and the LO-LARC patients were performed: patient characteristics, pathological complete response (pCR) rate, combined pCR + cCR rate, disease-free survival (DFS), and overall survival (OS). Results: Of 72 patients included in the analysis, 44(61%) were male, 49 (68%) were Caucasian, and 62 (86%) had clinical stage III disease. The study included 26 (36%) patients with YO-LARC (median age, 43 years) and 46 (64%) patients with LO-LARC (median age, 64 years). The comparison of patient characteristics that included gender, clinical stage, baseline carcinoembryonic antigen level, the distance of the tumor from the anal verge, presence of high-risk features, and histologic grade did not differ significantly between the groups. There were no statistically significant differences in pCR and combined pCR+cCR rates (p = 0.16) between the groups: YO-LARC, 12 % (3/26) and 15 % (4/26), respectively; LO-LARC, 22% (10/46) and 30% (14/46), respectively. Either group did not reach median DFS and OS after a median follow-up of 38 months for survivors. The estimated 5-year OS rates in patients with YO-LARC and LO-LARC were 86 % (95% confidence interval [CI], 69% to 100%) and 84% (95% CI, 68% to 100%), respectively (p = 0.92). The estimated 3-year DFS rates in patients with YO-LARC and LO-LARC were 67 % (95% CI, 50% to 89%) and 83% (95% CI, 72% to 95%), respectively (p = 0.19). Conclusions: The current retrospective analysis did not demonstrate significant differences in the pCR rates, combined pCR +cCR rates, DFS, or OS between the YO-LARC and LO-LARC patients treated with TNT.

Prognostic factors affecting the success of conversion chemotherapy in patients with unresectable liver metastases from initially colorectal cancer

Objective: To investigate the factors affecting the success of conversion therapy in patients with initially unresectable colorectal cancer liver metastases (CRLM) in order to provide evidence-based medical evidence for formulating individualized treatment strategies for patients. Methods: A retrospective case-control study was used in this study. Clinical data of 232 patients with initially unresectable CRLM receiving first-line systemic treatment in Sun Yat-sen University Cancer Center from January 2013 to January 2020 were collected, including 98 patients of successful conversion and 134 patients of failed conversion as control. Conversion therapy scheme: 38 patients received FOLFOXIRI regimen chemotherapy (irinotecan, oxaliplatin, calcium folinate and fluorouracil), 152 patients received FOLFOX regimen (oxaliplatin, calcium folinate and fluorouracil), 19 patients received FOLRIRI regimen (irinotecan, calcium folinate and fluorouracil), 23 patients received systemic chemotherapy combined with fluorouridine hepatic artery infusion chemotherapy; 168 patients received targeted therapy, including 68 of bevacizumab and 100 of cetuximab. Logistics analysis was used to compare the factors affecting the success of conversion therapy. The Kaplan-Meier method was used to calculate progression-free survival (PFS), and the Log-rank test was used for survival comparison. Results: Among 232 patients, 98 patients had successful conversions and 134 patients had failed conversions with a successful conversion rate of 42.2%, meanwhile 30 patients underwent simple hepatectomy and 68 underwent hepatectomy combined with intraoperative radiofrequency ablation. After first-line chemotherapy, 111 patients (47.8%) were partial remission, 57 patients (24.6%) were stable disease, and 64 patients (27.6%) were progression disease. During the median follow-up of 18.8 (1.0-87.9) months, 148 patients were dead or with tumor progression. The median PFS time of patients with successful conversion was longer than that of patients with failed conversion (31.0 months vs. 9.9 months, P<0.001). Univariate analysis found that the bilobar distribution of liver tumors (P=0.003), elevated baseline carcinoembryonic antigen (CEA) levels (P=0.024), tumor invasion of the portal vein (P=0.001), number of metastatic tumor>8 (P<0.001), non-FOLFOXIRI (P=0.005), and no targeted therapy (P=0.038) were high risk factors for the failed conversion therapy. The results of multivariate logistics analysis indicated that the number of metastatic tumor >8 (OR=2.422, 95%CI: 1.291-4.544, P=0.006), portal vein invasion (OR=2.727, 95%CI: 1.237-4.170, P=0.008) were the independent risk factors for failed conversion therapy, while FOLFOXIRI regimen (OR=0.300, 95%CI: 0.135-0.666, P=0.003) and targeted drugs (OR=0.411, 95%CI: 0.209-0.809, P=0.010) were independent protective factors for successful conversion therapy. Conclusions: The number of metastatic tumor and portal vein invasion are key factors that affect the outcomes of conversion therapy for initially unresectable CRLM. If a patient can tolerate chemotherapy, a combination program of three-drug and targeted therapy is preferred for the active conversion therapy.

'FLARE' of tumor marker in advanced gastric cancer treated with first-line systemic therapy.

Background:Transient tumor marker elevations caused by chemotherapy were defined as ‘Flare’ and have been demonstrated in some solid tumors. In clinical practice, we observed that some patients were accompanied by elevated tumor markers during treatment, but subsequent imaging proved that the treatment they received was effective.Objectives:We aimed to study the Flare and the prognosis in advanced gastric cancer.Design:This is an observational retrospective study. A total of 167 patients were enrolled in this study. Carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9 and CA125 values were obtained before the first, second, third, fourth, fifth and sixth cycles of treatment, respectively.Methods:Imaging for the first efficacy assessment was reviewed according to the Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) criteria. Kaplan–Meier analyses and log-rank tests were performed for overall survival (OS) analyses. Univariate and multivariate Cox analyses were used to determine the prognostic factor for OS and progression-free survival (PFS).Results:37.1% of patients were accompanied with at least one tumor marker Flare during the course of treatment. The median time to tumor marker peak was 24–30 days and the Flare duration lasted 49–53 days. Patients with tumor markers Flare had a worse OS. Flare may be associated with the use of 5-fluorouracil. Baseline CEA and CA125 levels were the independent prognostic factors for OS and baseline CA125 level was the independent prognostic factor for PFS.Conclusion:Initial elevation of tumor markers during treatment is not an indication of tumor progression. Patients with tumor markers ‘Flare’ may had a worse OS.

Serum Biomarker Status with a Distinctive Pattern in Prognosis of Gastroenteropancreatic Neuroendocrine Carcinoma

Objective: Gastroenteropancreatic neuroendocrine carcinoma (GEPNEC) is a major research focus, but the application of biomarkers to guide its prognostication and management is unsatisfying. Clinical values of conventional serum biomarkers, neuron-specific enolase (NSE), carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA199) warrant scrutiny. Methods: Patients diagnosed with GEPNEC with baseline NSE, CEA, and CA199 levels provided in Peking University Cancer Hospital were retrospectively studied. Relationships between biomarkers and prognosis were investigated by the χ2 test, Kaplan-Meier analysis, and univariate and multivariate Cox regression analyses. Results: A total of 640 GEPNEC patients were enrolled. NSE, CEA, and CA199 were elevated in 59.5%, 28.5%, and 21.3% of the population, respectively. Higher NSE had worse median overall survival (OS) (17.0 months vs. not reached, hazard ratio = 2.77 [2.06, 3.73], p < 0.001), and so did patients with higher CEA and CA199. Multivariable analysis confirmed that NSE and CA199 correlated with OS independently. Baseline NSE level and NSE remission predicted OS and the response of patients with first-line etoposide plus cisplatin (EP) treatment. Furthermore, we combined NSE/CEA/CA199 to segregate GEPNEC into novel subgroups, namely, adenocarcinoma-like NEC (ALN), neuroendocrine-like NEC (NLN), and triple-normal NEC (TNN). The groups shared distinctive clinicopathologic features and prognosis (21.0 months vs. 17.1 months vs. not reached, p < 0.001). The EP regimen remained the priority treatment option in NLN/TNN, while ALN was predisposed to “adenocarcinoma-like chemotherapy.” Conclusions: Elevation of NSE, CEA, or CA199 was common and independently indicates poor prognosis in GEPNEC patients. Serum biomarker-based subtypes suggest meaningful clinical implications and appropriate therapeutic approaches, illuminating promising ways to characterize the prognosis of GEPNEC.

Incidence, Risk Factors, and Outcomes from Conversion of Low-Grade to High-Grade Appendiceal Neoplasms for Patients Undergoing Multiple Cytoreductive Surgeries with Hyperthermic Intraperitoneal Chemotherapy

Conversion from low-grade to high-grade disease is known to occur following repeat cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC); however, the incidence rate, risk factors, and outcomes have not been studied. We conducted a retrospective review of multiple CRS/HIPEC cases for patients originally diagnosed with low-grade appendiceal neoplasms, and compared converted cases with non-converters. Primary outcomes were the incidence rate and risk factors for conversion, while secondary outcomes were effect on cytoreduction, overall survival (OS), and disease-free survival (DFS). Overall, 65 patients undergoing 134 cases of repeat CRS/HIPEC were identified; 11 patients converted to high-grade disease, an incidence rate of 16.92%. Converted cases averaged 4.4 years between CRS/HIPEC, versus 3.7 years for non-converters. Elevated baseline carcinoembryonic antigen (CEA) level, splenectomy at index CRS/HIPEC, and adjuvant chemotherapy utilization were statistically significant with conversion. Conversion had no impact on specific cytoreductive scores at repeat CRS/HIPEC (p=0.435). Evaluating the effect on OS from the index CRS/HIPEC conversion had no impact. Mean OS was 9.5 and 8.8 years for cases that remained low-grade compared with those that converted, respectively (p=0.668); however, when comparing OS from the time of conversion at repeat CRS/HIPEC, patients who progressed to high-grade disease had decreased survival at 4.4 versus 5.8 years (p=0.0317). There was no difference in DFS between non-converters and converters at 4.1 and 3.6 years, respectively (p=0.671). Conversion had no impact on OS from the index CRS/HIPEC but resulted in inferior survival from repeat surgery. Conversion was insignificant in regard to DFS, and should not be considered a contraindication to repeat CRS/HIPEC. Adjuvant chemotherapy should be avoided.