Baseline CA125 Levels Research Articles

Longitudinal and time-to-event modeling for the survival of advanced pancreatic ductal adenocarcinoma patients.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers especially at advanced stage. In order to analyze the dynamics of potential prognostic biomarkers and further quantify their relationships with the overall survival (OS) of advanced PDAC patients, we herein developed a parametric time-to-event (TTE) model integrated with longitudinal submodels. Data from 104 patients receiving standard chemotherapies were retrospectively collected for model development, and other 54 patients were enrolled as external validation. The longitudinal submodels were developed with the time-course data of sum of longest diameters (SLD) of tumors, serum albumin (ALB) and body weight (BW) using nonlinear mixed effect models. The model-derived metrics including model parameters and individual predictions at different time points were further analyzed in the TTE model, together with other baseline information of patients. A linear growth-exponential shrinkage model was employed to describe the dynamics of SLD, while logistic models were used to fit the relationship of time prior to death with ALB and BW. The TTE model estimated the ALB and BW changes at the 9th week after chemotherapies as well as the baseline CA19-9 level that showed most significant impact on the OS, and the model-based simulations could provide individual survival rate predictions for patients with different prognostic factors. This study quantitatively demonstrates the importance of physical status and baseline disease for the OS of advanced PDAC patients, and highlights that timely nutrition support would be helpful to improve the prognosis.

Effectiveness, safety, and biomarker analysis of lenvatinib plus toripalimab as chemo-free therapy in advanced intrahepatic cholangiocarcinoma: a real-world study

BackgroundTreatment options for advanced intrahepatic cholangiocarcinoma (ICC) are currently limited. Chemo-containing regimens are the mainstay treatments but associated with notable toxicity, poor tolerance, and reduced compliance, necessitating exploration of alternative therapies. Lenvatinib plus PD-1 inhibitors has shown substantial clinical activity in preliminary studies. This study aimed to assess the effectiveness and safety of lenvatinib plus toripalimab (a novel PD-1 antibody) as chemo-free therapy in advanced ICC.MethodsThis retrospective study included consecutive advanced ICC patients receiving lenvatinib plus toripalimab between February 2019 and December 2023. The main outcomes were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and safety. Prognostic factors and exploratory analyses for genetic alternations were also conducted.ResultsA total of 78 patients were included, with a median follow-up of 25.9 months. Median OS and PFS were 11.3 (95% CI: 9.5–13.1) and 5.4 (95% CI: 3.8–7.0) months, respectively. ORR was 19.2% and DCR was 75.6%. The incidence of grade 3 or 4 adverse events (AEs) was 50.0%, with no grade 5 AEs reported. Patients with normal baseline CA19-9 levels exhibited a higher ORR (p = 0.011), longer PFS (11.5 versus 4.6 months; HR 0.47; p=0.005), and OS (21.0 versus 9.7 months; HR 0.43; p=0.003). The presence of IDH1 mutations correlated with increased ORR (60.0% versus 8.9%, p=0.016).ConclusionLenvatinib plus toripalimab represents an effective and well-tolerated chemo-free therapeutic option for advanced ICC. Baseline CA19-9 levels and IDH1 mutations may serve as predictive treatment-related biomarkers.

Kinetics of CA19-9 decline in a randomized phase III study of irinotecan liposome injection, oxaliplatin, 5-fluorouracial/leucovorin (NALIRIFOX) or nab-paclitaxel plus gemcitabine (GEM+NABP) in patients who have not previously received chemotherapy for metastatic adenocarcinoma of the pancreas (NAPOLI 3).

687 Background: The NAPOLI 3 study (NCT04083235, N = 770) reported that NALIRIFOX improved overall survival (OS) vs Gem+NabP with manageable toxicity in 1L treatment of metastatic pancreatic adenocarcinoma. We explored changes in CA19-9 levels and their potential associations with efficacy as an important tumor marker in pancreatic adenocarcinoma. Methods: In NAPOLI 3, CA19-9 was evaluated at baseline and every 8 weeks until patients discontinued study treatment. The detection limit of CA19-9 was 8000 kU/L in this study. The Cox proportional hazards regression and logistic regression were employed to investigate the relationship between CA19-9 decrease and OS, progression-free survival (PFS), and overall response rate (ORR). Results: Patients with evaluable CA19-9 (levels =< 8000) at baseline and additional measurements at weeks 8 and 16 were included in the analysis (NALIRIFOX, n = 179; Gem+NabP, n = 194). The median baseline CA19-9 level was 378.0 and 409.7 kU/L for the NALIRIFOX and Gem+NabP arms, respectively. Overall, patients with (vs without) any CA 19-9 decrease by week 16 had a higher ORR (59.9% vs 35.2%; p = 0.002), a longer median PFS (9.2 vs 6.2 months; p < 0.001) and a longer median OS (14.2 vs 8.7 months; p = 0.005), respectively in a pooled analysis of the treatments. In the NALIRIFOX arm, patients with any CA19-9 decrease by week 16 had a higher confirmed ORR of 65.1% compared with those without at 42.4% ( p < 0.001), a median PFS of 9.5 vs 7.1 months ( p < 0.001) and a median OS of 15.4 versus 8.4 months ( p = 0.004), respectively. In the Gem+NabP arm, patients with CA19-9 decrease by week 16 had a higher ORR of 55.5% compared with those without at 23.8% ( p = 0.012), a median PFS of 7.6 versus 5.8 months ( p < 0.001) and a median OS of 13.7 versus 11.9 months ( p = 0.235), respectively. Conclusions: CA19-9 decrease by week 16 has the potential to be an early prognostic factor for OS, PFS and ORR. The results should be interpreted with caution as a considerable percentage of patients were excluded due to non-evaluable CA19-9 that exceeded the lab detection limit of 8000 kU/L. Clinical trial information: NCT04083235 .

Effects of the baseline prognostic factors on efficacy of the p62/SQSTM1-encoding plasmid combined with gemcitabine in patients with recurrent platinum-resistant ovarian cancer.

e17540 Background: We recently reported on the efficacy of the p62/SQTM1-encoding plasmid in patients with advanced, recurrent platinum-resistant ovarian cancer (PROC) receiving gemcitabine chemotherapy. Here we analyze the effects of baseline prognostic factors on efficacy. Methods: A prospective multicenter randomized study took place between 01/2020 and 08/2023. Cohort A (n=20) consisted of Gemcitabine 1000 mg/m2 days 1,8 every 3 weeks and Cohort B (n=20) consisted of Gemcitabine (Gem) 1000 mg/m2 days 1,8 every 3 weeks plus p62-plasmid 2.5 mg i.m. weekly. We stratified the patients into subgroups according to their baseline CA-125 level (normal vs high), number of lines of chemo (1 vs 2-3) received by a platinum-sensitive ovarian cancer (PSOC) patient before they became PROC, platinum-free interval (PFI) (up to 3 mo vs more than 3 mo), and presence or absence of peritoneal effusion. Cox proportional hazards regression analysis was utilized to determine effect of progression free survival (PFS). Results: The median follow-up was 13.8 months (mos). The median PFS was 2.8 mos in Gem (Arm A) and 7.2 mos in Gem + Plasmid (Arm B) respectively (p = 0.03). The overall response rate (ORR) by RESIST 1.1 was higher in the Gem +Plasmid arm: partial response (PR) - 5.0% and 20.0%, stable disease (SD) - 40.0% and 60.0%, and disease control rate 41.2 and 80% in Chemo and Plasmid arms respectively). In cohort A, all patients have progressed, whereas in Cohort B (Gem +Plasmid) 9 patients (45%) remained progression-free with the longest duration of response being 30 mo. Overall survival cannot be assessed yet. Analyzing prognostic factors with Cox Proportional Hazards Regression Analysis identified that the following factors increase p62 sensitivity: initial high CA-125 level PFS 2.5 and 6.5 (p = 0.01) in Arm A vs B, 1 line chemo vs 2 or 3 lines for PSOC, PFS 2.3 and 7.1 (p = 0.008) in Arm A vs B, and presence of peritoneal effusion PFS 2.4 and 7.6 (p = 0.008) in Arm A vs B (Table ). Conclusions: We observed maximal effect on PFS when combining the p62-encoding plasmid with Gem in the patients with the most dismal prognosis PROC: rapid progression (relapse as PROC after the first line of treatment and/or short PFI), in patients with an initial high level of CA-125, and/or pleural effusion. [Table: see text]

Serum cytokine levels are associated with tumor progression during FOLFIRINOX chemotherapy and overall survival in pancreatic cancer patients.

BackgroundBiomarkers predicting treatment response may be used to stratify patients with pancreatic ductal adenocarcinoma (PDAC) for available therapies. The aim of this study was to evaluate the association of circulating cytokines with FOLFIRINOX response and with overall survival (OS).MethodsSerum samples were collected before start and after the first cycle of FOLFIRINOX from patients with PDAC (n=83) of all disease stages. Overall, 34 circulating cytokines were analyzed with a multiplex immunoassay. In addition, changes in peripheral blood immune cell counts were determined by flow cytometry to correlate with differences in cytokine levels. Chemotherapy response was determined by CT scans with the RECIST 1.1 criteria, as disease control (n=64) or progressive disease (n=19) within eight cycles of FOLFIRINOX.ResultsPatients with high serum IL-1RA concentrations after one cycle of chemotherapy were less likely to have tumor progression during FOLFIRINOX (OR 0.25, P=0.040). Increase of circulating IL-1RA concentrations correlated with increase of total, classical (CD14+CD16-), and non-classical monocytes (CD14-CD16+), and dendritic cells. In multivariable cox regression, including the variables chemotherapy response outcome and baseline CA19-9 level, serum concentrations of IL-7 (HR 2.14, P=0.010), IL-18 (HR 2.00, P=0.020), and MIP-1β (HR 0.51, P=0.025) after one cycle of FOLFIRINOX showed correlations with OS.ConclusionsCirculating IL-1RA, IL-7, IL-18, and MIP-1β concentrations are biomarkers associated with FOLFIRINOX response in PDAC patients, suggesting an important role for specific immune cells in chemotherapy response and PDAC progression. Cytokine-based treatment might improve patient outcome and should be evaluated in future studies.

'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.

RECIST/CA-125 progression-free survival and the role of CA-125 surveillance in the phase III PAOLA-1/ENGOT-ov25 trial evaluating maintenance olaparib plus bevacizumab in patients with newly diagnosed advanced high-grade ovarian carcinoma

<h3>Objectives:</h3> In the PAOLA-1/ENGOT-ov25 primary analysis (NCT02477644), adding the PARP inhibitor olaparib to maintenance bevacizumab (bev) after first-line platinum-based chemotherapy with bev led to a significant progression-free survival (PFS) benefit vs placebo (pbo) + bev in patients (pts) with advanced high-grade ovarian cancer (HGOC), using modified RECIST v1.1 criteria (HR 0.59; 95% CI 0.49-0.72; <i>P</i><0.001; median PFS 22.1 vs 16.6 months) (Ray-Coquard <i>et al. NEJM</i> 2019). Limited evidence supports use of serum CA-125, a surrogate biomarker for progression, to detect relapse in pts receiving PARP inhibitor maintenance therapy. We evaluated RECIST/CA-125 progression and CA-125 surveillance in PAOLA-1. <h3>Methods:</h3> Pts with newly diagnosed, FIGO stage III-IV HGOC in response after platinum-based chemotherapy plus bev received bev (15 mg/kg q3w for 15 months) + olaparib (300 mg bid for 24 months) or pbo. Scans were performed every 24 weeks, or every 12 weeks if there was evidence of clinical or CA-125 progression. CA-125 levels were assessed every 12 weeks. Time to RECIST or CA-125 progression or death was a secondary endpoint; RECIST/CA-125 progression by biomarker status, response to initial therapy and CA-125 level at baseline were explored. <h3>Results:</h3> 537 pts were randomized to olaparib + bev and 269 to pbo + bev with median follow-up for PFS by RECIST/CA-125 of 24.2 vs 24.7 months (DCO 22 March 2019). In the ITT population, the benefit provided by olaparib + bev vs pbo + bev for PFS by RECIST/CA-125 (HR 0.58; 95% CI 0.48-0.70; <i>P</i><0.0001; median PFS 22.1 vs 15.4 months) was consistent with the primary analysis of PFS by RECIST. Of 462 pts with RECIST progression (ITT), 39% had RECIST progression alone and 45% had CA-125 progression more than 7 days before RECIST progression, with a median 2.4 months between CA-125 and RECIST progression (Table). In subgroup analyses, 49% of t<i>BRCA</i>m pts and 45% of HRD-positive pts had RECIST progression alone compared with only 37% of HRD-negative pts. 42% of pts with NED or CR had RECIST progression alone compared with 33% of pts with PR. 44% of pts with normal baseline CA-125 levels had RECIST progression alone compared with only 17% of pts with abnormal baseline CA-125 levels (<i>P</i><0.001). The rate of PFS events by RECIST/CA-125 was higher for pbo + bev vs olaparib + bev (74% vs 53%) (ITT). Of pts with RECIST progression, a similar proportion in each treatment arm had RECIST progression alone, including in subgroup analyses by biomarker status and response to initial therapy. <h3>Conclusions:</h3> Median PFS and HRs were consistent when progression was assessed by either RECIST or RECIST/CA-125 in PAOLA-1. Scans appear particularly important for detecting progression in HRD-positive pts, t<i>BRCA</i>m pts or pts with normal CA-125 levels at baseline as CA-125 levels did not seem to predict relapse in these pts. Results suggest that CA-125 surveillance alone may be sufficient to detect progression in most pts with abnormal baseline CA-125 levels when starting maintenance therapy.

Predictors of early recurrence following neoadjuvant chemotherapy and surgical resection for localized pancreatic adenocarcinoma.

Neoadjuvant chemotherapy (NAT) for pancreatic adenocarcinoma (PDAC) is increasingly being utilized. However, a significant number of patients will experience early recurrence, possibly negating the benefit of surgery. We aimed to identify factors implicated in early disease recurrence. A retrospective review of pancreaticoduodenectomies performed between 2005 and 2017 at our institution for PDAC following NAT was performed. A 6-month cut-off was used to stratify patients into early/late recurrence groups. Multivariate analysis was performed to identify predictors of recurrence. Of 273 patients, 64 (23%) developed early recurrence or died within 90 days of surgery. The median time to recurrence was 4 months (95% confidence interval [CI]: 2.2-4.3) in the early group versus 16 months (95% CI: 13.7-19.9) in the late group. The former had higher baseline and post-NAT Ca19-9 levels than the latter (472 vs. 153 IU/ml, p = 0.001 and 71 vs. 39 IU/ml, p = 0.005, respectively). A higher positive lymph node ratio significantly increased the risk of early recurrence (hazard ratio [HR]: 15.9, p < 0.001) while adjuvant chemotherapy was protective (HR: 0.4, p < 0.001). Our findings acknowledge the limitations of clinically measured factors used to ascertain response to NAT and underline the need for individualized molecular markers that take into consideration the specific tumor biology.

Predictive effects of preoperative serum CA125 and AFP levels on post-hepatectomy survival in patients with hepatitis B-related hepatocellular carcinoma.

The association between the serum levels of cancer antigen 125 (CA125; also termed MUC16) and the prognosis of patients with hepatocellular carcinoma (HCC) has not been widely reported to date. The aim of the present study was to determine the association between preoperative serum CA125 levels and prognosis of patients with hepatitis B virus (HBV)-related HCC after hepatectomy. The study included 306 patients with HBV-related HCC who underwent liver resection and were classified into four subgroups based on their baseline CA125 and α-fetoprotein (AFP) levels. The perioperative clinical data were compared and analyzed. Kaplan-Meier and Cox regression analyses were performed to determine the associations between patient clinicopathological characteristics and survival. The results revealed that the median follow-up time was 35 months. Patients with low preoperative serum CA125 levels presented with improved 3-year disease-free survival (DFS) (79.3 vs. 75.7%; P=0.278) and overall survival (OS) (84.4 vs. 77.1%; P=0.001) rates compared with those among patients with high preoperative serum CA125 levels. High preoperative serum CA125 levels were a risk factor associated with short DFS and OS rates in all patients. In patients with baseline AFP levels >100 ng/ml, low preoperative serum CA125 levels were significantly associated with prolonged DFS and OS rates (log-rank test P=0.002 and P=0.005, respectively). In patients with AFP levels ≤100 ng/ml, no significant differences were observed in DFS or OS rates between the high and low preoperative serum CA125 groups. Patients with high preoperative serum CA125 and AFP levels exhibited the worst prognosis (low DFS and OS rates). In conclusion, high baseline CA125 levels may be associated with a poor prognosis in patients with HBV-related HCC.

Pegylated liposomal doxorubicin in patients with epithelial ovarian cancer

ObjectiveTo evaluate the efficacy and safety of PLD in treating of in patients who experience epithelial ovarian, fallopian tubal, and peritoneal cancer progression within 12 months after the first-line platinum-based therapy.MethodsThis was an open-label, single-arm and multicenter clinical trial. The ORR was the interim primary objective, and the DCR, AEs and QOL were the secondary objectives. The impact of factors on efficacy outcomes, the change trend of CA125 and the artificial platinum-free interval were exploratory endpoints.ResultsTotally, 115 patients were enrolled in this study and included in the ITT population. Moreover, 101 patients were included in the safety population. The median follow-up time was 4 months (IQR 2–6). In the ITT population, the confirmed ORR was 37.4% (95% CI, 28.4–46.4%), and the DCR was 65.2% (95% CI, 56.4–74.1%). The previous response status to platinum-based chemotherapy and baseline CA125 levels were significantly correlated with the ORR. The ORR was significantly higher in patients with a CA125 decrease after the first cycle than in the patients with a CA125 increase. The most common grade 3 or higher AE was hand-foot syndrome (3 [3.0%] of 101 patients). No statistically significant differences existed between the baseline and the postbaseline questionnaires.ConclusionsFor patients who experience platinum-resistant and platinum-refractory relapse, the use of PLD may be acceptable because of the associated satisfactory efficacy, low frequency of AEs and high patient QOL. Moreover, a low CA125 level at baseline and a reduction in CA125 after the first cycle are predictive factors for satisfactory efficacy.

Prior history of acute pancreatitis predicts worse survival for patients with resectable pancreatic cancer

Presenter: Yitao Gong | Fudan University Shanghai Cancer Center Background: Mounting evidence has suggested that acute pancreatitis (AP) is a risk factor of pancreatic cancer (PC) and may accelerate oncogenesis in PC, but its role in survival in PC patients, especially in patients with resectable pancreatic cancer has not been investigated. The objective was to investigate the association of history of AP with survival among PC patients who have undergone surgical resection in a retrospective cohort-based study. Methods: In this retrospective cohort of 662 pancreatic cancer patients who underwent radical surgical resection, we evaluated survival by acute pancreatitis history prior to PC diagnoses using Kaplan-Meier methods and log-rank tests. Multivariate analyses for mortality were estimated using Cox proportional hazards model, adjusted for age, sex, tumour location, tumour grade, tumour stage, diabetes mellitus status, baseline CA19-9 level, adjuvant chemotherapy and adjuvant radiotherapy. Results: The log-rank tests showed that the patients with history of acute pancreatitis had worse overall survival compared to those without acute pancreatitis history (p = 0.007). The multivariable-adjusted HR for mortality comparing participants with acute pancreatitis to those without was 1.709 (95% CI: 1.187- 2.459, P-value = 0.004). After categorizing patients with history of acute pancreatitis into recent ( < 2 years) and remote history (≥ 2 years) of AP, patients with recent history of AP, rather than patients with remote history of AP, were found to have significantly worse survival (P-value = 0.007) than those without AP history. Conclusion: Our findings indicate that history of acute pancreatitis, especially recent history of acute pancreatitis, is associated with worse survival in resectable pancreatic cancer patients.

Mutant KRAS and TP53 with high mutation allelic frequency in ctDNA as poor outcome predictors in metastatic pancreatic cancer.

e15763 Background: This study was to investigate the feasibility and the prognostic value of circulating tumor DNA (ctDNA) in metastatic pancreatic cancer (MPC). Methods: From 2015 to 2018 in our center, 40 MPC patients treated with nab-paclitaxel based first-line chemotherapy were prospectively collected both tumor tissue and blood samples, in which the genomic profiling of 425 genes was identified by next-generation sequencing. High mutation allelic frequency (MAF) was defined &gt; 30% and &gt; 5% in tumor tissue and blood, respectively. Kappa statistics were used to compare mutant (mt) genes in tissue and ctDNA. Progression-free and overall survival (PFS, OS) were assessed with Kaplan-Meier and Cox methods. Results: Among 40 MPC patients, tumor tissue and blood samples were available in 34 and 38 patients for somatic and germline alternation test, respectively. The most commonly mutant gene were KRAS (31/34 in tissue with a median MAF of 29.4%, 29/38 in ctDNA with a mMAF of 8.2%), and TP53 (28/34 in tissue with a mMAF of 31.1%, 25/38 in ctDNA with a mMAF of 7.4%). Moderate agreement was seen between ctDNA and tumor tissue (mt KRAS: κ = 0.54, P = 0.001; mt TP53: κ = 0.74, P &lt; 0.001). Mutation in CDNK2A and SMAD4 genes were detected in 8 and 6 patients in tissue and ctDNA, respectively. Germline alternation was found in 7 genes in 9 patients (9/40). High MAF of mt KRAS (r = 0.51, P = 0.005) or mt TP53 (r = 0.50, P = 0.005) in ctDNA was correlated with high CA199 levels (&gt; 5000 u/ml) at baseline. MT KRAS in tissue with high MAF was associated with poor OS (high 7.5m vs low 10.1m, P = 0.001) in univariate and multivariate analyses (HR 3.87, 95%CI 1.47 to 10.19). Univariate analyses showed mt KRAS and mt TP53 in ctDNA with high MAF were associated with poor PFS ( KRAS and TP53: high 3.4m and 3.0m vs low 6.1m and 5.7m, P = 0.001 and P = 0.004, respectively) and OS ( KRAS and TP53: high 5.3m and 5.3m vs low 12.6m and 10.1m, P &lt; 0.001, respectively). The presence of ctDNA in any above four mt driver gene with high MAF was associated with poor PFS (HR 3.79, 95%CI 1.71 to 8.42) and OS (HR 7.21, 95%CI 2.69 to 19.34) in multivariate COX model, when adjusted by age, sex, tumor differentiation, and baseline CA199 level. Conclusions: The presence of mt KRAS and mt TP53 with high MAF in ctDNA was associated with worse PFS and OS in MPC patients. Peripheral ctDNA testing demonstrated an alternative promising prognostic biomarker for MPC patients before treatment.

Predictors of neoadjuvant chemotherapy efficacy in localized pancreatic head cancer: A 15-year experience at a high volume pancreatic cancer center.

e15724 Background: Surgery followed by adjuvant chemotherapy (SF) is the standard approach for localized pancreatic adenocarcinoma (PC). Although neoadjuvant chemotherapy (NC) is being increasingly used, its efficacy remains debatable. This study aims to identify baseline factors associated with benefit from NC as compared to SF for PC. Methods: Review of a prospectively maintained database of resected localized head PC undergoing NC or SF at a tertiary referral hospital from 2002 to 2018. Baseline factors investigated included clinical stage by EUS (7th edition AJCC), CT vessel involvement, and serum CA19-9. Baseline CA19-9 levels were grouped into mild (37-200), moderate (200-900), and marked elevations (≥ 900). Patients with baseline serum CA19-9 &lt; 37 IU/dL were excluded from the analysis. Results: In total, 269 patients were evaluated: 165 (61%) received NC and 104 (39%) had SF. Mean patient age was 68.3 years and 50% were females. Of these, 42% had stage IIB, 44% had N1 disease, and 38% had vascular involvement. Compared to SF approach, NC was associated with improved median survival for CA19-9 of &lt; 200 IU/dL (30 vs 21 months, p = 0.08), 200-900 IU/dL (32 vs 17 months, p &lt; 0.01), and the ≥900 IU/dL (33 vs 12 months, p &lt; 0.01) groups. On Cox regression, NC was the only baseline factor predictive of improved survival in the groups with moderate (HR:0.35,[95% CI:0.20-0.62];p &lt; 0.01) and marked (HR:0.36,[95% CI:0.18-0.71];p &lt; 0.01) pretreatment CA19-9 elevation. Notably, NC was not predictive of improved survival in the cohort with mild CA19-9 elevation. Conclusions: This study identifies a cohort of patients that benefits from neoadjuvant chemotherapy over a surgery first approach for localized pancreatic head cancer. Elevation in baseline CA19-9 may serve as the strongest indicator for chemotherapy before resection.

The predictive factors of gastric cancer recurrence after the completion of adjuvant chemotherapy in advanced gastric cancer.

the administration of adjuvant chemotherapy after a curative resection is accepted as the standard treatment to improve the prognosis of advanced gastric cancer. Nevertheless, the prognosis of recurrence-related gastric cancer is still not clinically satisfactory. We aimed to assess the therapeutic yield of a radical gastrectomy with D2 lymphadenectomy (R0 resection) and the completion of adjuvant chemotherapy. The predictive risk factors for recurrence were also assessed. a retrospective cohort study was designed with patients diagnosed with advanced gastric cancer. Patients with an R0 resection who had completed adjuvant chemotherapy were included in the study. data from 130 patients who had undergone an R0 resection and had completed six cycles of adjuvant chemotherapy were analyzed. The chemotherapy compliance rate was 63.11% and the overall recurrence rate was 36.9%. The lymph node ratio (LNR), which was defined as the number of metastatic lymph nodes divided by the retrieved lymph nodes, was a significant risk factor in the lymph node-positive group (p < 0.01). This parameter had a relatively high sensitivity to predict recurrence compared with the 7th and 8th edition of the AJCC staging system, with an area under the curve of 0.735 (95% confidence interval: 0.639-0.832). Baseline CA19-9 level was a risk factor in the lymph node-negative group (p = 0.01). LNR and baseline CA19-9 levels, as simple markers, had strong predictive values for the recurrence of advanced gastric cancer. With regard to recurrence, more potent adjuvant therapy should be considered in high-risk patients.

Baseline splenic volume as a surrogate marker of FOLFIRINOX efficacy in advanced pancreatic carcinoma.

BackgroundThe FOLFIRINOX regimen is the standard first-line treatment for advanced pancreatic adenocarcinoma (aPDAC). However, because of its potential toxicity, predictive biomarkers could help clinical decision-making.MethodsA cohort of 97 aPDAC patients treated with first-line FOLFIRINOX were studied. The association between splenic volume and progression-free survival (PFS) and overall survival (OS) was evaluated using univariate and multivariable Cox analyses. The external validation cohort was composed of 117 patients treated with Gemcitabine and 52 patients treated with FOLFIRINOX.ResultsIn the training cohort, the splenic volume of 97 patients was measured at baseline and at the end of therapy. The spleen size increased in 81% of patients, with at least a 50% increase in 27% of patients. Baseline splenomegaly predicted PFS (HR 1.812, 95% CI = [1.036–3.169]; p = 0.03) and OS (HR 1.983, 95% CI = [1.085–3.624]; p = 0.02) in the training cohort. These results were then validated in an external cohort of patients who were treated with FOLFIRINOX excluding those in the control cohort who were treated with gemcitabine. In a multivariate model based on the CoxBoost method, the following were selected as predictive markers of FOLFIRINOX efficacy (AUC = 0.81): performance status, liver metastasis, baseline Ca199 and CEA levels and baseline splenomegaly. The predictive ability of the model was validated in the external cohort that was also treated with FOLFIRINOX.ConclusionsBaseline splenomegaly is a predictive marker of a poor response to FOLFIRINOX in aPDAC and remained predictive when associated with other clinical variables.

CA125 suppresses amatuximab immune-effector function and elevated serum levels are associated with reduced clinical response in first line mesothelioma patients

ABSTRACTThe tumor-shed antigen CA125 has recently been found to bind certain monoclonal antibodies (mAbs) and suppress immune-effector mediated killing through perturbation of the Fc domain with CD16a and CD32a Fc-γ activating receptors on immune-effector cells. Amatuximab is a mAb targeting mesothelin whose mechanism of action utilizes in part antibody-dependent cellular cytotoxicity (ADCC). It is being tested for its therapeutic activity in patients with mesothelioma in combination with first line standard-of-care. To determine if CA125 has immunosuppressive effects on amatuximab ADCC and associated clinical outcomes, post hoc subgroup analysis of patients from a Phase 2 study with primary diagnosed stage III/IV unresectable mesothelioma treated with amatuximab plus cisplatin and pemetrexed were conducted. Analysis found patients with baseline CA125 levels no greater than 57 U/m (∼3X the upper limit of normal) had a 2 month improvement in progression free survival (HR = 0.43, p = 0.0062) and a 7 month improvement in overall survival (HR = 0.40, p = 0.0022) as compared to those with CA125 above 57 U/mL. In vitro studies found that CA125 was able to bind amatuximab and perturb ADCC activity via decreased Fc-γ-receptor engagement. These data suggest that clinical trial designs of antibody-based drugs in cancers producing CA125, including mesothelioma, should consider stratifying patients on baseline CA125 levels for mAbs that are experimentally determined to be bound by CA125.

Nab-paclitaxel plus gemcitabine versus FOLFIRINOX as the first-line chemotherapy for patients with metastatic pancreatic cancer: retrospective analysis.

Purpose nab-paclitaxel plus gemcitabine (AG) and FOLFIRINOX have been established as standard first-line treatment in metastatic pancreatic cancer (mPC). We performed retrospective analysis comparing the efficacies of AG and FOLFIRINOX in daily practice setting. Materials and Methods We analyzed 308 patients who presented initially as mPC and received AG (n = 149) or FOLFIRINOX (n = 159) as first-line treatment between 2013 and 2016. Primary endpoints were progression-free survival (PFS) and overall survival (OS). Result There were no significant differences between the two groups in terms of baseline characteristics, except older age and higher Charlson Comorbidity Index (CCI) score in AG group. The response rates (34% vs 34%) and median PFS (6.8 vs 5.1months) were comparable between two groups (p = 0.88 and p = 0.19, respectively), while median OS was significantly better with AG than FOLFIRINOX (11.4 vs 9.6months; p = 0.002). Elevated baseline CA19-9 level and liver metastasis were independent adverse prognostic factors for PFS and OS. In subgroup analyses, PFS with AG was better in patients with age ≥ 65years, peritoneal metastasis, and higher CCI than that with FOLFIRINOX. Conclusion Both AG and FOLFIRINOX showed comparable efficacy outcomes in daily practice setting. AG might be preferentially considered in patients with peritoneal metastasis, comorbid medical conditions or old age.

Efficacy of nab-paclitaxel plus gemcitabine (AG) vs. FOLFIRINOX as first line chemotherapy for metastatic pancreatic cancer (mPC): Real world experiences.

354 Background: AG and FOLFIRINOX have been established as standard first-line treatment in mPC patients based on the improved efficacy compared to gemcitabine monotherapy. Because there was no head-to-head comparison between these regimens, however, there is lack of data which regimen is preferable in patients with mPC. Therefore, we performed retrospective analysis comparing the efficacy of AG and FOLFIRINOX in daily practice setting. Methods: We analyzed a total of 308 patients with confirmed mPC who received AG (n = 149) or FOLFIRINOX (n = 159) as first-line treatment between 2013 and 2016 at Asan Medical Center, Seoul, Korea. Primary endpoint was overall survival (OS) and secondary endpoints were progression-free survival (PFS) and overall response rates (ORR). Results: Median age was slightly older in AG group than FOLFIRINOX group (62 vs. 60 years, p = 0.02). Except this, there was no significant difference between the two groups in terms of baseline characteristics including sex (male, AG/FOLFIRNOX): 56%/67%, ECOG performance status (0-1): 97%/99%, pancreatic head location: 32%/40%, and baseline CA19-9 level ( &gt; UNL): 77%/82%. ORR (28% vs. 31%) and disease control rate (74% vs. 74%) did not differ between two groups (p = 0.45, and p = 0.96, respectively). Although there was no significant difference in PFS between the two groups (AG: median 6.8 months [95% CI: 5.8-7.8] vs. FOLFIRINOX: 5.1 months [95% CI: 4.2-5.9]; p = 0.15), OS was significantly better in AG group compared to FOLFIRINOX group (median 12.3 months [95% CI: 11.0-13.7] vs. 9.7 months [95% CI, 8.1-11.4]; p = 0.001). Among the patients who showed progression, 81% (180/223) received second-line chemotherapy and there was no difference between the two groups (AG vs. FOLFIRINOX: 76% vs. 85%, p = 0.09). 5-FU monotherapy or combination with oxaliplatin were given in 97% (73/75) of patients in AG group and gemcitabine-based regimens (including 2 cases of AG) were given in 97% (102/105) of patients in FOLFIRINOX group. Conclusions: Both AG and FOLFIRINOX are feasible and active as first-line treatment for patients with mPC. In daily practice setting, AG showed comparable efficacy outcomes with FOLFIRINOX.

Association of increased neutrophil-lymphocyte ratio after curative surgery with prognosis in patients with locally advanced esophagogastric adenocarcinoma.

63 Background: The neutrophil-lymphocyte ratio (NLR) is associated with the inflammatory status of patients with some cancers. We hypothesize that increased NLR was associated with prognosis in patients with stage II/III esophagogastric adenocarcinoma. Methods: We retrospectively analyzed 220 patients with stage II/III gastric cancer who underwent curative resection with suitable lymphadenectomy at our hospital, between 2000 and 2014. All patients underwent baseline staging, including blood tests, computed tomography, and endoscopic biopsy. The relationship between NLR and clinical outcomes was analyzed by univariate and multivariate analyses. Results: Average age was 67.9 [95% confidence interval (CI); 43.8, 92.1] years, and majority of the patients were male. After surgery, 111 (50.5%) patients underwent adjuvant chemotherapy, most of all patients received S-1 according to Japanese treatment guideline. Median follow-up time was 74.8 (95% CI; 69.9, 79.7) months. The preoperative NLR was 3.2 (95% CI; -4.2, 10.6), whereas the postoperative NLR was 3.0 (95% CI; -6.9, 12.8). In univariate analyses, age, stage, preoperative NLR, baseline CA19-9 levels, postoperative white blood cell (WBC) count, postoperative hemoglobin levels, postoperative NLR, increased NLR after surgery and adjuvant chemotherapy were associated with overall survival (OS). In multivariate analyses, age ( p &lt; 0.001), stage ( p = 0.001), and increased NLR after surgery ( p = 0.048) were associated with OS. The prognosis of patients with increased NLR after surgery was observed to be worse than that of those with decreased NLR after surgery ( p = 0.001). Conclusions: Our findings indicated that increased NLR after curative resection was associated with poor OS in patients with locally advanced esophagogastric adenocarcinoma, suggesting that perioperative increased NLR was a potentially useful marker for individual therapy.

FCGR2A and FCGR3A Genotypes Correlate with Farletuzumab Response in Patients with First-Relapsed Ovarian Cancer Exhibiting Low CA125

Farletuzumab is a humanized monoclonal antibody that binds to folate receptor alpha and elicits an anti-tumor response via immune effector activity. Recent studies from a global phase 3 trial in ovarian cancer patients treated with carboplatin/taxane plus farletuzumab found that the tumor-produced CA125 protein can suppress farletuzumab function via perturbing its engagement to the activating Fc-γ receptors CD32a (FCGR2A) and CD16a (FCGR3A). Previous reports have indicated that naturally occurring polymorphisms in both of these receptors may play a role in their ability to engage therapeutic antibodies and elicit an optimal immune response via antibody-dependent cellular cytotoxicity (ADCC). In light of the importance of farletuzumab ADCC function for optimal tumor cell killing, we evaluated the frequency of FCGR2A-131H/R and FCGR3A-158V/F polymorphisms in 461 consenting patients from this global clinical study and their association with clinical outcome to placebo versus farletuzumab treatment. Here, we show that farletuzumab has enhanced binding to FCGR3A-158V high-affinity receptor and has an enhanced clinical outcome in patients with low baseline CA125 levels and at least 1 high-affinity allele of FCGR2A or FCGR3A.