Early Pancreatic Cancer Research Articles

Novel computer aided diagnostic system using hybrid neural network for early detection of pancreatic cancer

One of the most dangerous tumours in the world, pancreatic cancer (PC), has an unimpressive five-year survival rate of about 5%. An early PC identification is crucial for raising patient survival rates. Diagnosis of PC requires computed tomography (CT), magnetic resonance imaging (MRI) with magnetic resonance cholangiopancreatography (MRCP), or biopsy. The proposed CAD design approach includes image preprocessing, segmentation, feature extraction, and classification phases. Preprocessing is done by using Colour conversion and an isotropic diffusion filter approaches. After that, proposed Fuzzy K-NN Equality algorithm used in segmentation procedures. Deep Learning with feature extraction is used as a classification tool. Tumour cells are classified using the features collected from the pancreatic sample. Train values and testing datasets are part of the image classification criterion. For the purpose of detecting pancreatic cancer, a hybrid Deep Convolutional Neural Network with Deep Belief Network (DCNN_DBN) algorithm is used. According to the experimental findings, the current CAD system offers massive prospects as well as safety in the automated diagnosis of both benign as well as malignant cancers and produces the accuracy of 99.6%. Using this classifier, computing complexity is massively diminished. The suggested technique could be enhanced to detect more pancreatic cancer cell abnormalities.

Maintaining early diagnosis of pancreatic adenocarcinoma in Japan: Local resilience against COVID-19

Background and aimsThis study evaluated the impact of the coronavirus disease 2019 (COVID-19) pandemic on pancreatic adenocarcinoma (PA) practice in our region and discussed the effects of our institution's regional collaborative system, the “Early Stage Pancreatic Cancer Diagnosis Project," which was originally unrelated to this study's purpose. MethodsWe retrospectively investigated 150 patients with PA at Yokohama Rosai Hospital by defining three time periods: before (C0), during the first year (C1), and during the second year (C2) of the COVID-19 pandemic. ResultsAmong the three periods (C0, C1, and C2), there were significantly less patients with stage I PA (14.0%, 0%, and 7.4%, p = 0.032) in C1, and significantly more patients with stage III PA (10.0%, 28.3%, and 9.3%, p = 0.014) in C1. The pandemic significantly prolonged the median durations from disease onset to patients’ first visits (28, 49, and 14 days, p = 0.012). In contrast, there was no significant difference in the median durations from referral to first visit to our institution (4, 4, and 6 days, p = 0.391). ConclusionsThe pandemic advanced the stage of PA in our region. Although the pancreatic referral network remained functional during the pandemic, there were delays from disease onset to patients' first visit to healthcare providers, including clinics. While the pandemic caused temporary damage to PA practice, the routine regional collaboration provided by our institution's project allowed for early resilience. A notable limitation is that the impact of the pandemic on PA prognosis was not evaluated.

Circulating tumor DNA (ctDNA) and disease recurrence in early stage pancreatic cancer.

e16313 Background: Surgical resection with neoadjuvant and/or adjuvant chemotherapy remains to be the cornerstone in treatment for early-stage pancreatic adenocarcinoma. Disease recurrence after curative intent treatment remains to be very common, and early detection of disease recurrence remains challenging. Recent studies explored the role of ctDNA in guiding adjuvant treatment in colon cancer, but its role in pancreatic cancer remains unknown. Methods: Through comprehensive chart review, we identified patients who: 1. Diagnosed with early-stage pancreatic adenocarcinoma; 2. Underwent curative intent surgery at our institution from 2019 to 2021; 3. Have postoperative tissue informed ctDNA results with commercially available assay (Signatera, by Natera Inc). Results: A total of 14 patients, including 7 males and 7 females, were included in the study. Depending on location of tumor, types of surgery included Whipple procedure (N = 13) and distal pancreatectomy (N = 1). The median age at time of surgery was 62 years (Range: 41-83 years). Two patients received neoadjuvant chemotherapy, and 13 patients received adjuvant chemotherapy. Two patients also received adjuvant radiation. A total of 41 ctDNA readings were obtained. The median time from surgery to first ctDNA assay was 2.4 months. First post-op ctDNA was positive in 6 patients, all of whom received adjuvant chemotherapy but still experienced clinical recurrence after a median of 3.7 months. The median overall survival of those ctDNA+ patients was 11.4 months. In the remaining 8 patients, the median progression free survival was 14 months, with clinical recurrence being observed in 4 patients. Median overall survival was not reached at median follow up of 30.5 months (one patient died at 6 months without disease recurrence, and another died at 14 months with progressive disease). In the 4 patients who had clinical recurrence despite initially negative ctDNA, ctDNA turned positive 1 month before clinical recurrence in 1 patient. However, in the other 3 patients, recurrence occurred 3.1, 1.9 and 3.5 months after the most recent negative ctDNA result. Conclusions: Our study demonstrated that positive ctDNA reliably predicts clinical recurrence in early-stage pancreatic cancer after surgery, with a positive predictive value of 100%. Negative result appears to be less reliable. This may be explained by different shedding pattern and test sensitivity. Larger scale study is underway to further evaluate its role in determining prognosis and guiding adjuvant treatment.

Selective extended dissection for pancreaticoduodenectomy is associated with better survival in pancreatic cancer patients: retrospective cohort study.

Pancreatic ductal adenocarcinoma is a highly malignant tumor with relatively poor survival. Surgery is the first choice for treating patients with early pancreatic cancer. However, the surgical approach and the extent of resection for patients with pancreatic cancer are currently controversial. The authors optimized the procedure of standard pancreaticoduodenectomy to selective extended dissection (SED), which is based on the extrapancreatic nerve plexus potentially invaded by the tumor. The authors retrospectively analyzed the clinicopathological data of patients with pancreatic adenocarcinoma who underwent radical surgery in our center from 2011 to 2020. Patients who underwent standard dissection (SD) were matched 2:1 to those who underwent SED using propensity score matching. The log-rank test and Cox regression model were used to analyze survival data. In addition, statistical analyses were performed for the perioperative complications, postoperative pathology, and recurrence pattern. A total of 520 patients were included in the analysis. Among patients with extrapancreatic perineural invasion (EPNI), disease-free survival was significantly longer in those who received SED than in those who received SD (14.5 months vs. 10 months, P <0.05). The incidence of metastasis in No. 9 and No. 14 lymph nodes was significantly higher in patients with EPNI. In addition, there was no significant difference in the incidence rate of perioperative complications between the two surgical procedures. Compared with SD, SED exhibits a significant prognostic benefit for patients with EPNI. The SED procedure aiming at specific nerve plexus dissection displayed particular efficacy and safety in resectable pancreatic ductal adenocarcinoma patients.

Health Disparities in Presentation, Treatment, Genomic Testing, and Outcomes of Pancreatic Cancer in Hispanic and Non-Hispanic Patients

BackgroundThere are few conflicting results regarding the treatment and outcomes of Hispanic patients with pancreatic cancer. This study comprehensively evaluated the differences in baseline characteristics, treatments, genomic testing, and outcomes among Hispanic (H) and Non-Hispanic (NH) patients with early-stage (ES) and late-stage (LS) pancreatic cancer (PC).MethodsThis is a retrospective analysis from 2013 to 2020 of 294 patients with pancreatic ductal adenocarcinoma; data collected included patient demographics, clinical characteristics, treatment regimens, response, germline and somatic genetic testing, and survival outcomes. Excluded those with insufficient data. Univariate comparisons used parametric and nonparametric tests as appropriate to evaluate for differences between H and NH groups. Fisher’s exact tests were performed to evaluate the difference in frequency. Kaplan–Meier and Cox regression analysis assessed the survival.ResultsThe analysis included 198 patients who had a late-stage disease and 96 patients with early-stage disease at the time of diagnosis. Among the early-stage patients, the median age at diagnosis was 60.7 years in the H versus 66.7 years in the NH (p = 0.03). No other differences were observed in baseline characteristics, treatments offered, and median overall survival (NH 25 vs. H 17.7 months, p = 0.28). Performance status, negative surgical margins, and adjuvant therapy were clinically significant and univariable with improved OS (p < 0.05), regardless of ethnicity. Hispanic patients with early pancreatic cancer were noted to be at a greater risk of death with a statistically significant hazard ratio of 3.1 (p = 0.005, 95% CI, 1.39–6.90). Among the late-stage patients, Hispanic patients with ≥ 3 predisposing risk factors for pancreatic cancer were 44% vs. 25% of NH (p = 0.006). No significant differences were noted in baseline characteristic treatments, progression-free, and median overall survivals (NH 10.0 vs. 9.2 months, p = 0.4577). In the late-stage genomic testing, germline testing performed in NH 69.4% vs. H 43.9% (p = 0.003) revealed no difference among groups. For the somatic testing, the pathogenic variants with actionable mutations were 2.5% of NH and 17.6% of H patients (p = 0.03).ConclusionHispanic patients with early-stage pancreatic adenocarcinoma present at a younger age and with more risk factors in the late stage. These patients have significantly lower overall survival compared to their non-Hispanic counterparts. Hispanic patients in our study were 2.9 less likely to receive germline screening and more like to have somatic genetic actionable pathogenic variants. Overall, only a minority of all patients were enrolled in a pancreatic cancer clinical trial or offered genomic testing, highlighting a critical need and missed opportunity in advancing progress and improving outcomes for this disease, mainly in the underrepresented Hispanic population.

Abstract 1008: A novel biomarker and therapeutic target for early pancreatic cancer

Abstract Purpose: Pancreatic cancer (PC) has a grim prognosis, and an early diagnostic biomarker has been highly desired. The molecular link between diabetes and PC has not been well established. Methods: Bioinformatics screening was performed for a serum PC marker. Experiments in cell lines (5 PC and 1 normal cell lines), mouse models, and human tissue staining (37 PC and 10 normal cases) were performed to test asprosin production from PC. Asprosin’s diagnostic performance was tested with serums from multi-center cohorts (347 PC, 209 normal, and 55 additional diabetic patients) and evaluated according to PC status and stages which was compared with that of CA19-9. Results: Asprosin, a diabetes-related hormone, was found from the bioinformatics screening, and its production from PC was confirmed. Serum asprosin levels from multi-center cohorts yielded an age-adjusted diagnostic area under the curve (AUC) of 0.987 (95% confidence interval [CI] = 0.961 to 0.997), superior to that of CA19-9 (AUC = 0.876, 95% CI = 0.847 to 0.905), and a cut-off of 7.18 ng/mL, at which the validation set exhibited a sensitivity of 0.957 and a specificity of 0.924. Importantly, the performance was maintained in early stage PC, consistent with the tissue staining. A slightly lower performance against additional diabetic patients (n = 55) was restored by combining asprosin and CA19-9 (AUC = 0.985, 95% CI = 0.975 to 0.995). Conclusion: Asprosin is presented as an early-stage PC serum marker that may provide clues for PC-induced diabetes. Larger prospective clinical studies are warranted to solidify its utility. Citation Format: Min Seok Park, Kyung Hee Jung, Sang Eun Kim, Yun Ji Lee, Sunghyouk Park, Soon-Sun Hong. A novel biomarker and therapeutic target for early pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1008.

Abstract 1511: Origin of synchronous or metachronous multiple pancreatic cancers

Abstract Introduction: The majority of patients with pancreatic cancer are inoperable at the time of diagnosis and even those cases with successful tumor resection for early-stage tumors frequently had second tumors within the remaining pancreas shortly after the surgery, contributing to a poor clinical outcome. Moreover, synchronous multiple pancreatic cancers were often reported. One of the long-standing issues about such synchronous and/or metachronous multiple pancreatic cancers is their clonal origins. In this study, we aimed to reveal the origin of multiple pancreatic cancers using an unbiased detection of somatic mutations in primary and metachronous cancers as well as adjacent precursor lesions. Methods: Serially obtained formalin-fixed paraffin-embedded surgical specimens from 18 patients who had undergone curative surgery for an early-stage pancreatic cancer were subjected to laser microdissection for the enrichment of tumor and precancerous lesions, from which DNA was extracted and analyzed for somatic mutations using whole-exome sequencing (WES) with matched normal DNA. Based on shared and private mutations across different samples, we interrogated history of clonal evolution of these lesions. Results: We analyzed 18 patients with multiple pancreatic cancers of 2 metachronous and synchronous, 14 metachronous, and 2 synchronous tumors. In metachronous cases, pathology for primary cancer were margin-negative in all patients, and the median interval between the initial and second surgery was 38.9 months (7 - 85 months). In addition, a total of 20 pancreatic intraepithelial neoplasia (PanIN) from 5 of these cases were analyzed. We identified a median of 66 (range: 31-232) and 20 (14-42) somatic mutations in cancer and PanIN lesions, respectively. None of the patients have known pathogenic germline variants. All samples had one or more driver mutations. In most cases (N=17), sharing many somatic mutations, multiple tumors had a common clonal origin. In another synchronous case, the synchronous tumors shared only one mutation, suggesting that they were clonally independent tumors. By contrast, none of the mutations other than hotspot KRAS mutations were shared between precursor and cancer lesions. While multiple independent clones were observed in precancerous lesions, most of multiple cancers originated from a common ancestor. Moreover, negative pathology of the margins at the initial surgery suggested that those multiple lesions arose from distant dissemination or metastasis, rather than contiguous, intraductal invasion. Conclusions: In conclusion, our study suggests that even early pancreatic cancer might be disseminated within the pancreas and contribute to synchronous and metachronous cancers. Citation Format: Tomonori Hirano, Nobuyuki Kakiuchi, Yasuhide Takeuchi, Tomomi Nishimura, Toshihiko Masui, Kazuyuki Nagai, Takayuki Anazawa, Sachiko Minamigushi, Hironori Haga, Norimitsu Uza, Hiroshi Seno, Yuzo Kodama, Atsuhiro Masuda, Takeshi Tanaka, Seishi Ogawa, Hiroko Tanaka, Satoru Miyano. Origin of synchronous or metachronous multiple pancreatic cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1511.

Utility of promoter hypermethylation in malignant risk stratification of intraductal papillary mucinous neoplasms

BackgroundIntraductal papillary mucinous neoplasms (IPMNs), a type of cystic pancreatic cancer (PC) precursors, are increasingly identified on cross-sectional imaging and present a significant diagnostic challenge. While surgical resection of IPMN-related advanced neoplasia, i.e., IPMN-related high-grade dysplasia or PC, is an essential early PC detection strategy, resection is not recommended for IPMN-low-grade dysplasia (LGD) due to minimal risk of carcinogenesis, and significant procedural risks. Based on their promising results in prior validation studies targeting early detection of classical PC, DNA hypermethylation-based markers may serve as a biomarker for malignant risk stratification of IPMNs. This study investigates our DNA methylation-based PC biomarker panel (ADAMTS1, BNC1, and CACNA1G genes) in differentiating IPMN-advanced neoplasia from IPMN-LGDs.MethodsOur previously described genome-wide pharmaco-epigenetic method identified multiple genes as potential targets for PC detection. The combination was further optimized and validated for early detection of classical PC in previous case–control studies. These promising genes were evaluated among micro-dissected IPMN tissue (IPMN-LGD: 35, IPMN-advanced neoplasia: 35) through Methylation-Specific PCR. The discriminant capacity of individual and combination of genes were delineated through Receiver Operating Characteristics curve analysis.ResultsAs compared to IPMN-LGDs, IPMN-advanced neoplasia had higher hypermethylation frequency of candidate genes: ADAMTS1 (60% vs. 14%), BNC1 (66% vs. 3%), and CACGNA1G (25% vs. 0%). We observed Area Under Curve (AUC) values of 0.73 for ADAMTS1, 0.81 for BNC1, and 0.63 for CACNA1G genes. The combination of the BNC1/ CACNA1G genes resulted in an AUC of 0.84, sensitivity of 71%, and specificity of 97%. Combining the methylation status of the BNC1/CACNA1G genes, blood-based CA19-9, and IPMN lesion size enhanced the AUC to 0.92.ConclusionDNA-methylation based biomarkers have shown a high diagnostic specificity and moderate sensitivity for differentiating IPMN-advanced neoplasia from LGDs. Addition of specific methylation targets can improve the accuracy of the methylation biomarker panel and enable the development of noninvasive IPMN stratification biomarkers.

Outcomes of FOLFIRINOX and gemcitabine plus nab-paclitaxel in patients with early recurrent pancreatic cancer after adjuvant S-1: A propensity score–matching analysis.

707 Background: An oral fluoropyrimidine, S-1, is a standard adjuvant (adj) chemotherapy practice in Japan for patients (pts) with resected pancreatic cancer (PC). Patients experiencing recurrence after adj S-1 administration are treated with FOLFIRINOX (FFX), including intravenous fluoropyrimidine, or gemcitabine plus nab-paclitaxel (GN), which is commonly used as the first-line chemotherapy approach in pts with advanced PC. Some pts have good response to FFX with acceptable toxicity levels even though recurrence within 6 months (mo) after the last S-1 administration is attributed to PC refractory to fluoropyrimidine. To the best of our knowledge, there is no clinical study comparing FFX and GN in this particular population. Methods: This multi-center, retrospective study included pts with PC that had a recurrence-free interval (RFI) &lt; 6 mo from the last adj S-1 administration and were treated with FFX or GN between December 2013 and 2018. The decision to administer FFX or GN was taken by the attending physicians. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response, and serious adverse events (SAE). The OS and PFS were calculated from the time of initiation of treatment with FFX or GN. To adjust confounding factors in the comparison of FFX with GN, propensity score-matching (PSM) analysis was performed. Potentially confounding factors were identified by univariate analysis for OS, and statistical significance was set at p &lt; 0.1. Results: A total of 284 (FFX; 50, GN; 234) pts were enrolled from 32 institutions in Japan. Potential confounding factors comprised curability, pathological T/N, tumor differentiation status, reasons for the end of S-1 administration, chemotherapy regimen, performance status, serum albumin/C-reactive protein/carbohydrate antigen 19-9 levels, and presence or absence of liver metastasis before initiating the administration of FFX or GN. After PSM, 43 pts each in the FFX and GN groups were compared in pairs. The patient characteristics, excluding age, in the matched pair were well-balanced; the proportion of pts aged &lt; 65 years in the FFX and GN groups was 61% and 30%, respectively. The median OS and PFS were longer in the GN group than in the FFX group; OS was 14.5 vs. 11.1 mo (hazard ratio [HR], 0.61; 95% confidence interval [CI], 0.38-0.97); PFS was 7.1 vs. 5.1 mo (HR, 0.65; 95% CI, 0.41-1.02). The objective response, disease control rates, and observed SAE in the GN and FFX groups were 20/19%, 80/66%, and 14/19% respectively. Seventy-two percent of the pts in the GN group received subsequent therapies of FFX/S-1/FOLFIRI/FOLFOX (28/12/9/5%); while 77% of the FFX group pts received subsequent therapies of GN/GEM (54/7%). Conclusions: Real world data suggests that GN may be recommended in PC pts with RFI &lt; 6 mo from the last administration of adj S-1.

Vibrational spectroscopy - are we close to finding a solution for early pancreatic cancer diagnosis?

Pancreatic cancer (PC) is an aggressive and lethal neoplasm, ranking seventh in the world for cancer deaths, with an overall 5-year survival rate of below 10%. The knowledge about PC pathogenesis is rapidly expanding. New aspects of tumor biology, including its molecular and morphological heterogeneity, have been reported to explain the complicated "cross-talk" that occurs between the cancer cells and the tumor stroma or the nature of pancreatic ductal adenocarcinoma-associated neural remodeling. Nevertheless, currently, there are no specific and sensitive diagnosis options for PC. Vibrational spectroscopy (VS) shows a promising role in the development of early diagnosis technology. In this review, we summarize recent reports about improvements in spectroscopic methodologies, briefly explain and highlight the drawbacks of each of them, and discuss available solutions. The important aspects of spectroscopic data evaluation with multivariate analysis and a convolutional neural network methodology are depicted. We conclude by presenting a study design for systemic verification of the VS-based methods in the diagnosis of PC.

Exploration of Risk Factors for Pancreatic Cancer and Development of a Clinical High-Risk Group Rating Scale.

(1) Background: There are few studies on people at high risk for clinical pancreatic cancer (PC). We aimed to explore the risk factors of PC and establish a scale for identifying high-risk populations of clinical PC. (2) Methods: We conducted a matched case-control study, retrospectively collecting demographic data and common clinical indicators from all subjects. Logistic regression was used to explore the risk factors of PC. Based on these factors, we created a high-risk population rating scale, which showed a higher diagnostic value. (3) Results: 385 cases and 428 controls were finally enrolled in our study. Multivariate analysis showed that body mass index (BMI) below 18.5 kg/m2 (OR 5.944, 95%CI: 1.759~20.084), smoking (OR 2.745, 95%CI: 1.555~4.844), new-onset diabetes (OR 5.239, 95%CI: 2.091~13.125), low high-density lipoprotein cholesterol (HDL-C) levels (OR 1.790, 95%CI: 1.044~3.069), and carbohydrate antigen 19-9 (CA19-9) levels no less than 35 U/mL (OR 160.328, 95%CI: 83.392~308.243) were associated with an increased risk of PC, whereas high total cholesterol (TC) levels were related to a lower risk of PC (OR 0.392, 95%CI: 0.211~0.730). The high-risk population scale, whose area under the receiver operating curve reached 0.948 (p < 0.001), showed a greater clinical diagnostic value. (4) Conclusions: Smoking history, new-onset diabetes, BMI, TC, HDL-C, and CA19-9 levels were associated with the risk of PC. The high-risk population rating scale might be used for early clinical PC screening.

Neoadjuvant therapy impact in early pancreatic cancer: "bioborderline" vs. "non-bioborderline".

To analyze the results of the neoadjuvant treatment of patients in our center with early pancreatic cancer. Eighty-four patients with early pancreatic cancer (I-II) were included, of which 59 were considered "bioborderline" (carbohydrate antigen [CA] 19-9 > 37 U/L), and 25 were considered "non-bioborderline" (CA19-9 < 37 U/L). The R0 resection rate, presence of negative nodes, survival, and recurrence rates were analyzed in two groups, the NEO group (neoadjuvant + surgery) and the non-NEO group (upfront surgery). A 28.6% pathologic complete response was observed in the NEO group of the whole sample. The residual R0 was 85.7%, and nodes were negative in 78.6% of the patients in the NEO group of bioborderline patients. All non-bioborderline patients treated with neoadjuvant were R0, and no affected nodes were observed in any of them. The median overall survival (OS) in patients with elevated CA19-9 levels in the NEO group was 31.4 months vs. 13.1 months in the non-NEO (log-rank test p = 0.006), with a 62% relative reduction in the mortality rate (hazard ratio = 0.38, 95% confidence interval: 0.20-0.79; p = 0.008). The median OS in patients with normal CA19-9 levels in the NEO group was 65.9 months vs. 16.2 months in the non-NEO group, without statistically significant differences between the two but with a trend toward significance (log-rank test p = 0.08). A neoadjuvant strategy seemed to improve local control and the survival of patients with early pancreatic cancer, both those with elevated CA19-9 and normal marker levels.

Neoadjuvant Chemotherapy and Stereotactic Body Radiation Therapy in Patients with Early Onset Pancreatic Cancer: Clinical Outcomes and Toxicity

<h3>Purpose/Objective(s)</h3> Little is known on optimal management of patients with early onset pancreatic cancer (EOPC), including the role of radiation therapy. As such, we report on a cohort of patients with EOPC (age <55 years) who was treated with neoadjuvant chemotherapy and stereotactic body radiation therapy (SBRT). <h3>Materials/Methods</h3> This was a single institution retrospective review of patients with EOPC who were treated with upfront chemotherapy followed by SBRT with or without surgical resection. Endpoints included overall survival (OS), local progression-free survival (LPFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), and treatment-related toxicity. Next-generation sequencing (NGS) was performed on select patient tumor specimens. <h3>Results</h3> From 2016-2021, 47 patients met the inclusion criteria. Median age was 50.4 years (range, 36.4 – 54.7 years). Median induction chemotherapy duration was 4 months (range, 2.5 – 9 months). The majority (46/47, 97.9%) of patients received 33 Gy in 5 fractions. Following SBRT, 43 patients (91%) underwent surgical exploration, with extent of vascular involvement on post-SBRT imaging precluding exploration in 4 patients (9%). Gross resection was achieved in 33 patients (70.2%), with intraoperative metastatic disease precluding resection in 8 patients (17%) and intraoperative extent of vascular involvement of the primary tumor precluding resection in 4 patients (9%). Median OS, LPFS, DMFS, and PFS were 14.2 months, 11.6 months, 8.9 months, and 8.1 months respectively. Six-month and 1-year LPFS were 88.3% and 45.4%, respectively. Chemotherapy duration (≥ 4 months) was associated with improved median OS (16.5 vs 10.1 months, p=0.005), LPFS (10.1 vs 4.9 months, p=0.002), DMFS (9.7 vs 5.2 months, p=0.014), and PFS (9.7 vs 5.2 months, p=0.020). Normalization of CA 19-9 (≤ 34 vs > 34 U/ml) after chemotherapy was associated with improved median DMFS (not reached vs 5.6 months, p=0.003) and PFS (11.3 vs 5.6 months, p=0.022). Grade 3+ rates of chemotherapy and radiation-related toxicity were 14.9% and 2.1% respectively. Clavien-Dindo 3b toxicity rate was 3.0%. A total of 15 patients underwent NGS, with mutations being found in <i>KRAS</i> (10/15, 66.7%), <i>TP53</i> (7/15, 46.7%), <i>NOTCH 1/2</i> (3/15, 20%), <i>CDK2NA</i> (2/15, 13.3%), and <i>SMAD4</i> (1/15, 6.7%). <h3>Conclusion</h3> Multi-modality therapy for EOPC was administered with low toxicity, but outcomes remain suboptimal. Induction chemotherapy duration ≥ 4 months and normalization of CA 19-9 after chemotherapy were associated with improved outcomes, suggesting a role for extended durations of systemic therapy titrated to CA 19-9 response before transitioning to local therapy. The high rate of local failure and the low rate of grade 3+ toxicity also suggest a role for intensifying local therapy in this population, such as radiation dose escalation, expansion of the radiation target volume, and more aggressive surgical techniques.

Mobile device integrated graphene oxide quantum dots based electrochemical biosensor design for detection of miR-141 as a pancreatic cancer biomarker

Among all cancer forms, pancreatic cancer has one of the highest mortality rates. Early pancreatic cancer detection is crucial at this time. For this purpose, in this study, a simple and sensitive electrochemical sensor was developed for the detection of microRNA (miRNAs-(miR-141)), which is a pancreatic cancer biomarker. Graphene oxide quantum dots (GoQdot) modified and thiolated single-stranded DNA detection probes (thiol-ss-DNA) on Screen Printed Electrode (SPE) interacted with miR-141 and gave significant results on electron transfer. Differential Pulse Voltammetry (DPV) and Cyclic Voltammetry (CV) measurements showed that the binding of ss-DNA to SPE and the concentration-dependent increase of miR-141 decreased electron transfer. The current values obtained for 2.3 and 6.1 nM miR-141 concentrations were calculated, and the detection limit (LOD) was found to be 0.091 pM and the limit of quantitation (LOQ) was calculated as 0.27 pM. Significant results were obtained by connecting to mobile devices with SPE. The resulting sensor system had label-free, fast, and easy application possibilities. This sensor system, obtained with GoQdot, has achieved innovative outputs for the early detection of this type of cancer diseases.

RNA-sequencing for transcriptional profiling of whole blood in early stage and metastatic pancreatic cancer patients.

We investigated the transcriptional profile of whole blood in early and metastatic stages of pancreatic cancer (PaC) patients to identify potential diagnostic factors for early diagnosis. Blood samples from 18 participants (6 healthy individuals, 6 patients in early stage (I/II) PaC, and 6 patients in metastatic PaC) were analyzed by RNA-sequencing. The expression levels of identified genes were subsequently compared with their expression in pancreatic tumor tissues based on TCGA data reported in UALCAN and GEPIA2 databases. Overall, 331 and 724 genes were identified as differentially expressed genes in early and metastatic stages, respectively. Of these, 146 genes were shared by early and metastatic stages. Upregulation of PTCD3 and UBA52 genes and downregulation of A2M and ARID1B genes in PaC patients were observed from early stage to metastasis. TCGA database showed increasing trend in expression levels of these genes from stage I to IV in pancreatic tumor tissue. Finally, we found that low expression of PTCD3, A2M, and ARID1B genes and high expression of UBA52 gene were positively correlated with PaC patients survival. We identified a four-gene set (PTCD3, UBA52, A2M, and ARID1B) expressed in peripheral blood of early stage and metastatic PaC patients that may be useful for PaC early diagnosis.

S31 Cole Relaxation Frequency: A Parameter for Pancreatic Cancer Detection

Introduction: Pancreatic cancer (PC) accounts for half a million new cases and 4.7% of the world's cancer-related deaths in 2020. It is considered one of the most lethal malignancies with a global survival rate of only 5%. Innovative imaging and endoscopic techniques are being studied to improve the accuracy of PC detection. Endoscopic ultrasound (EUS) guided tissue acquisition is currently the gold standard for sampling pancreatic masses. EUS guided fine needle biopsy has been considered superior to fine needle aspiration, but both are limited by the subjectivity of endoscopists and invasiveness of the procedure. Nonetheless, at present, there is no standard procedure for PC detection. The Cole Relaxation Frequency (CRF) – a derived electrical bioimpedance signature for cancer detection proposed by NovaScan – has been proven to quantitatively detect cancer in breast, skin, and lung tissues. The aim of this pilot study was to determine if the CRF based NovaScan technology can detect cancer in pancreatic tissues. Methods: CRF was measured with NovaScan technology in multiple locations (Figure A) on the pancreas samples in a cohort of n=26 mice, of which 15 were KPC (model of pancreatic ductal adenocarcinoma), 2 were KC (model of pancreatic neoplasia), and 9 were wild type controls. NovaScan determined cancer presence when the CRF parameter was measured above 1 MHz (Figure:B,C). Outcomes were compared to histopathology results for each of these samples to determine the specificity and sensitivity of the NovaScan device. Results: From histology, 12 KPC pancreases were confirmed as cancerous, 9 controls were confirmed as noncancerous, while 5 pancreases (3 KPC and 2 KC) presented with pancreatic intraepithelial neoplasia (PanIN), a precancerous condition. NovaScan technology identified 4 out of 5 PanIN samples as cancerous. Considering the entire cohort (n=26), specificity and sensitivity were 100% and 94%, respectively. If PanIN samples were excluded, specificity and sensitivity were both 100% (n=21). Conclusion: Future development of NovaScan CRF based technology into a rapid onsite evaluation or an endoscopic device would provide an affordable means for accurate and quantitative PC detection that guides or substitutes pancreatic biopsy acquisition. Identification of malignant precursors indicates the technological capability of NovaScan’s device to detect early stage PCs. Further technology development could allow for the distinction between cancerous and precancerous lesions.Figure 1.: (A) KPC pancreas sample placed on Novascan’s electrode array for a series of spectral bioimpedance measurements. A zoom in of the electrode with a pancreas sample is also shown. White rectangles indicate multiple locations measured across the sample. Spectral impedance scans for a control mouse (B) and a KPC mouse (C). The examination of CRF peak properties was used for cancer identification in pancreas samples. For the control mouse the CRF peaks fall below the threshold of 1 MHz, determining no cancer. For the KPC mouse several scans have CRF peaks above the threshold of 1 MHz, determining cancer presence.

Usefulness of Practitioner-Led Pancreatic Cancer Screening.

The 5-year survival rate for pancreatic cancer has improved (10%) but remains worse than that for other cancers. Early pancreatic cancer diagnosis is challenging, and delayed diagnosis can delay treatment, which impairs survival. Practitioners do not promptly refer cases to a general hospital, causing delayed discovery. Herein, we aimed to examine the usefulness of the Pancreatic Cancer Project in Matsue, whose objective is to detect pancreatic cancer in patients presenting at any medical institution in Matsue City. Clinical data were extracted from medical records, and abdominal ultrasonography and tumor marker blood level assessments were performed (n = 234; median age, 71 [range, 41–94] years; 51% male). Cases with abnormal abdominal ultrasonography or blood test findings were referred for specialist imaging and followed up. The pancreatic cancer detection rate was 6.0% (n = 14); all cases were referred to a general hospital by practitioners within 1 month. Patients had stage IA (n = 1), IIA (n = 6), IIB (n = 2), III (n = 1), and IV (n = 4) disease. Overall, pancreatic cancer could be detected at an earlier stage (I–II), but referral to a general hospital by visiting practitioners should be prompt. The Pancreatic Cancer Project in Matsue may help improve the detection and prognosis of pancreatic cancer.

Effect of surgery on the survival of elderly patients with early stage pancreatic cancer: A propensity‐matched analysis

AbstractBackground and objectivesResearch about the effect of surgery in geriatric patients with early stage pancreatic ductal adenocarcinoma (PDAC) is limited, and it remains a subject of much debate. The purpose of this study was to evaluate the role of surgery on the survival of elderly patients with T1‐3N0M0 PDAC and to further investigate the prognosis of these patients undergoing different surgical methods.MethodsPatients aged ≥65 with T1‐3N0M0 PDAC diagnosed in 2004–2016 were collected from the Surveillance, Epidemiology, and End Results database. The imbalance of baseline characteristics was reduced by propensity score matching. We used the log‐rank tests to evaluate overall survival (OS) and cancer‐specific survival (CSS) among different groups. Univariate and multivariate Cox regression analysis was utilized to explore prognostic factors in PDAC.ResultsIn total, 6363 patients were enrolled. After matching, 1110 patients were paired. We found that surgery could provide better survival (p &lt; 0.001). Moreover, compared with those who underwent partial resection or larger resection, patients who underwent local tumor destruction had poorer OS and CSS (p &lt; 0.001). However, no statistically significant survival differences were shown between the partial resection group and the larger resection group (p &lt; 0.001).ConclusionSurgical intervention could confer a survival benefit to elderly patients with early stage PDAC. Additionally, these patients could benefit from more radical operations, and radical operations with reasonable extents are advocated rather than too aggressive methods.

Cost-effectiveness of MicroRNA for Pancreatic Cancer Screening in Patients With Diabetes

The study aimed to assess the cost-effectiveness of microRNA compared with carbohydrate antigen 19-9, abdominal ultrasound, magnetic resonance imaging, endoscopic ultrasound, computed tomography, positron emission tomography, and no screening for pancreatic cancer (PC) screening in patients with diabetes. We developed a state-transition model from a health care payer perspective and a lifetime horizon. We targeted 3 hypothetical cohorts of patients with long-standing type 2 diabetes (LSD), new-onset diabetes (NOD), and LSD having intraductal papillary mucinous neoplasm (IPMN), aged 40, 50, 60, and 70 years. The main outcomes were costs, quality-adjusted life-years, life expectancy life-years, incremental cost-effectiveness ratios, and deaths from PC. In the base-case analysis, abdominal ultrasound in patients with LSD and microRNA in patients with NOD and LSD having IPMN were the most cost-effective for all age groups. Cost-effectiveness was sensitive to PC incidence and the cost of microRNA. Probabilistic sensitivity analysis showed that microRNA was 42% to 54% cost-effective for NOD and 76% to 78% cost-effective for LSD having IPMN at a willingness-to-pay level of US $100,000 per quality-adjusted life-year gained. MicroRNA prevented 30,641 PC deaths in diabetic patients compared with no screening. In patients with NOD and LSD having IPMN, microRNA-based PC screening is cost-effective and recommended for early PC detection.

Identification of novel early pancreatic cancer biomarkers KIF5B and SFRP2 from “first contact” interactions in the tumor microenvironment

BackgroundPancreatic cancer is one of the most difficult cancers to detect early and most patients die from complications arising due to distant organ metastases. The lack of bona fide early biomarkers is one of the primary reasons for late diagnosis of pancreatic cancer. It is a multifactorial disease and warrants a novel approach to identify early biomarkers.MethodsIn order to characterize the proteome, Extracellular vesicles (EVs) isolated from different in vitro conditions mimicking tumor-microenvironment interactions between pancreatic cancer epithelial and stromal cells were analyzed using high throughput mass spectrometry. The biological activity of the secreted EVome was analyzed by investigating changes in distant organ metastases and associated early changes in the microbiome. Candidate biomarkers (KIF5B, SFRP2, LOXL2, and MMP3) were selected and validated on a mouse-human hybrid Tissue Microarray (TMA) that was specifically generated for this study. Additionally, a human TMA was used to analyze the expression of KIF5B and SFRP2 in progressive stages of pancreatic cancer.ResultsThe EVome of co-cultured epithelial and stromal cells is different from individual cells with distinct protein compositions. EVs secreted from stromal and cancer cells cultures could not induce significant changes in Pre-Metastatic Niche (PMN) modulation, which was assessed by changes in the distant organ metastases. However, they did induce significant changes in the early microbiome, as indicated by differences in α and β-diversities. KIF5B and SFRP2 show promise for early detection and investigation in progressive pancreatic cancer. These markers are expressed in all stages of pancreatic cancer such as low grade PanINs, advanced cancer, and in liver and soft tissue metastases.ConclusionsProteomic characterization of EVs derived from mimicking conditions of epithelial and stromal cells in the tumor-microenvironment resulted in the identification of several proteins, some for the first time in EVs. These secreted EVs cannot induce changes in distant organ metastases in in vivo models of EV education, but modulate changes in the early murine microbiome. Among all the proteins that were analyzed (MMP3, KIF5B, SFRP2, and LOXL2), KIF5B and SFRP2 show promise as bona fide early pancreatic cancer biomarkers expressed in progressive stages of pancreatic cancer.