Recurrent Pancreatic Cancer Research Articles

Possibility of Neoadjuvant Treatment for Radiologically Judged Resectable Pancreatic Cancer.

Survival remains poor even after resection of pancreatic cancer and the postoperative recurrence rate is extremely high. Thus, neoadjuvant treatment may improve outcomes for resectable pancreatic cancer (RPC). This study evaluated the efficacy of neoadjuvant therapy for radiologically judged RPC. A prospectively maintained institutional database was reviewed to identify patients who underwent potentially curative resection of radiologically judged RPC. Patient characteristics and intermediate-term outcomes were compared between groups that received neoadjuvant treatment or upfront surgery (UFS). We identified 353 eligible patients, including 55 patients who received neoadjuvant chemoradiotherapy (CRT group), 53 patients who received neoadjuvant gemcitabine plus nab-paclitaxel (GnP group), and 245 patients who underwent UFS (UFS group). The cumulative rates of pancreatic cancer recurrence at 2 years after pancreatic surgery were 49.5% in the UFS, 48.1% in the CRT group, and 52.7% in the GnP group. The recurrence rate tended to be improved after neoadjuvant treatment, although the difference was not significant at this follow-up point. While the clinical TNM classifications were noticeably different from the final pathological findings, the clinical and pathological TNM classifications were more similar in the groups that underwent neoadjuvant treatment. Neoadjuvant treatment can help identify good surgical candidates and avoid unnecessary laparotomy. Our results also suggest that neoadjuvant therapy might help improve the preoperative diagnostic accuracy for patients with RPC.

A nationwide randomized controlled trial on additional treatment for isolated local pancreatic cancer recurrence using stereotactic body radiation therapy (ARCADE)

BackgroundDisease recurrence is the main cause of mortality after resection of pancreatic ductal adenocarcinoma (PDAC). In 20–30% of resected patients, isolated local PDAC recurrence occurs. Retrospective studies have suggested that stereotactic body radiation therapy (SBRT) might lead to improved local control in these patients, potentially having a beneficial effect on both survival and quality of life. The “nationwide randomized controlled trial on additional treatment for isolated local pancreatic cancer recurrence using stereotactic body radiation therapy” (ARCADE) will investigate the value of SBRT in addition to standard of care in patients with isolated local PDAC recurrence compared to standard of care alone, regarding both survival and quality of life outcomes.MethodsThe ARCADE trial is nested within a prospective cohort (Dutch Pancreatic Cancer Project; PACAP) according to the ‘Trials within Cohorts’ design. All PACAP participants with isolated local PDAC recurrence after primary resection who provided informed consent for being randomized in future studies are eligible. Patients will be randomized for local therapy (5 fractions of 8 Gy SBRT) in addition to standard of care or standard of care alone. In total, 174 patients will be included. The main study endpoint is survival after recurrence. The most important secondary endpoint is quality of life.DiscussionIt is hypothesized that additional SBRT, compared to standard of care alone, improves survival and quality of life in patients with isolated local recurrence after PDAC resection.Trial registrationClinicalTrials.gov registration NCT04881487. Registered on May 11, 2021.

Stereotactic Body Radiation Therapy is Safe and Feasible for the Treatment of Locally Recurrent Pancreatic Adenocarcinoma after Curative Resection

<h3>Purpose/Objective(s)</h3> Locoregional relapse rates following surgical resection of pancreatic cancer can be as high as 45-50%. The majority of these patients are not candidates for re-resection due to co-morbidities and/or technically unresectable disease, highlighting the role of non-invasive options such as radiation therapy. The purpose of this study was to report on a cohort of radiation-naïve patients who developed isolated local recurrence following surgical resection and were subsequently treated with stereotactic body radiation therapy (SBRT). <h3>Materials/Methods</h3> Patients who were treated with SBRT for locally recurrent pancreatic cancer after initial curative resection were retrospectively reviewed. Clinical outcomes were calculated from completion of SBRT and included overall survival (OS), local progression-free survival (LPFS), distant metastasis-free survival (DMFS), and progression-free survival (PFS). Univariate and multivariate analyses were performed to identify variables associated with clinical outcomes. Kaplan-Meier analysis was performed for survival outcomes. Toxicity was assessed using the Common Terminology Criteria for Adverse Events version 4.0. <h3>Results</h3> From September 2012 to November 2018, a total of 19 patients were treated with SBRT for locally recurrent pancreatic cancer after initial surgical resection. No patients had prior radiation. The most common SBRT dose/fractionation was 33 Gy in 5 fractions (12/19, 63.1 %), followed by 25 Gy in 5 fractions (4/19, 21.0%), 28 Gy in 5 fractions (1/19, 5.3%), 27 Gy in 4 fractions (1/19, 5.3%), and 26.4 Gy in 4 fractions (1/19, 5.3%). Peri-SBRT chemotherapy was administered to 10 patients, in the pre-SBRT (3/19, 15.7%) and/or post-SBRT (8/19, 42.1%) setting. Median OS was 17.1 months, with 6-month and 1-year OS rates of 94.4% and 69.6%, respectively. A total of 9 patients (47.4%) developed local failure after SBRT. Pattern of first failure after SBRT was distant in 7 patients (46.7%), local in 5 patients (33.3%), and synchronous distant and local in 3 patients (20.0%). One patient developed local failure after developing distant disease first. Of the 9 local failures, 3 (33.3%) were out-of-field, involving the porta hepatis (n=1), pancreaticojejunostomy (n=1), and pancreatic remnant (n=1). Median LPFS was 22.2 months, with 6-month and 1-year LPFS rates of 86.9% and 63.2%, respectively. A biologically effective dose (BED₁₀) < 54.8 Gy was associated with inferior LPFS (1-year LPFS, 25.0% vs 80.2%, p<0.009). Median DMFS and PFS were 15.6 months. There was 1 case (5.3 %) of grade 3 gastric perforation. There were no cases of grade 4-5 toxicity events. <h3>Conclusion</h3> Stereotactic body radiation therapy for local recurrence after initial curative resection is safe and feasible. A BED₁₀ < 54.8 Gy was significantly associated with inferior local control, and one-third of local failures were out-of-field. Further studies investigating dose escalation and optimal treatment volumes in the locally recurrent setting are warranted.

Mutant p53 driven-LINC00857, a protein scaffold between FOXM1 and deubiquitinase OTUB1, promotes the metastasis of pancreatic cancer

Tumour metastasis is the major adverse factor for recurrence and death in pancreatic cancer (PC) patients. P53 mutations are considered to be the second most common type of mutation in PC and significantly promote PC metastasis. However, the molecular mechanisms underlying the effects of p53 mutations, especially the regulatory relationship of the protein with long noncoding RNAs (lncRNAs), remain unclear. In the present study, we demonstrated that the lncRNA LINC00857 exhibits a significantly elevated level in PC and that it is associated with poor prognosis; furthermore, TCGA data showed that LINC00857 expression was significantly upregulated in the mutant p53 group compared with the wild-type p53 group. Gain- and loss-of-function experiments showed that LINC00857 promotes the metastasis of PC cells. We further found that LINC00857 upregulates FOXM1 protein expression and thus accelerates metastasis in vitro and in vivo. Mechanistically, LINC00857 bound simultaneously to FOXM1 and to the deubiquitinase OTUB1, thereby serving as a protein scaffold and enhancing the interaction between FOXM1 and OTUB1, which inhibits FOXM1 degradation through the ubiquitin–proteasome pathway. Interestingly, we found that mutant p53 promotes LINC00857 transcription by binding to its promoter region. Finally, atorvastatin, a commonly prescribe lipid-lowering drug, appeared to inhibit PC metastasis by inhibiting the mutant p53-LINC00857 axis. Taken together, our results provide new insights into the biology driving PC metastasis and indicate that the mutant p53-LINC00857 axis might represent a novel therapeutic target for PC metastasis.

Impact of margin accentuation with intraoperative irreversible electroporation on local recurrence in resected pancreatic cancer

BackgroundThe purpose of this study was to evaluate the rates of local recurrence and margin positivity in patients with borderline resectable pancreatic cancer after pancreatectomy with or without irreversible electroporation with margin accentuation. MethodsProspective data for preoperative stages IIB (borderline resectable) and III were evaluated, with 75 patients undergoing pancreatectomy with irreversible electroporation with margin accentuation compared to 71 patients who underwent pancreatectomy alone from March 2010 to November 2020. ResultsBoth irreversible electroporation with margin accentuation and pancreatectomy-alone groups were similar for body mass index, Charleston comorbidity index, and sex. The irreversible electroporation with margin accentuation group had significantly greater preoperative stage III (irreversible electroporation 83% vs pancreatectomy alone 51%; P = .0001), with similar tumor location (head 64% vs 72%) and tumor size (median 2.9 vs 2.8). Neoadjuvant/induction chemotherapy and prior radiation therapy was similar in both groups (irreversible electroporation with margin accentuation 89% vs 72%). Surgical therapy included a greater percentage of pancreaticoduodenectomy in the pancreatectomy-alone group. Despite greater stage and greater percentage of margin positivity (irreversible electroporation with margin accentuation 27% vs 20%; P = not significant), rates of local recurrence were similar. The mean disease-free interval for local recurrence from time of diagnosis was similar (irreversible electroporation with margin accentuation 15.8 vs 16.5 pancreatectomy alone; P = not significant) and time of treatment (irreversible electroporation with margin accentuation 9.4 vs 10.5 months; P = not significant). Overall survival was improved with the irreversible electroporation with margin accentuation group, with a mean of 34.2 months versus 27.9 months in the pancreatectomy-alone group. ConclusionIrreversible electroporation with margin accentuation is safe and effective in stages IIB and III pancreatic adenocarcinomas that are technically resectable. Despite higher margin positivity rates, the time to local recurrence and the effects of recurrence were the same in the pancreatectomy-alone group.

Treatment outcomes of nanoliposomal irinotecan as second-line chemotherapy after gemcitabine and nab-paclitaxel in metastatic and recurrent pancreatic cancer.

To compare the treatment outcomes of nanoliposomal-irinotecan (nal-IRI) plus fluorouracil and leucovorin (5-FU/LV) and modified FOLFIRINOX (mFFX) as second-line treatment after gemcitabine with nab-paclitaxel (GnP) for metastatic and recurrent pancreatic cancer. We retrospectively analyzed consecutive patients with metastatic or recurrent pancreatic cancer treated with nal-IRI plus 5-FU/LV or mFFX after first-line GnP treatment between March 2014 and October 2021 in our hospital. Patient characteristics, treatment outcomes and adverse events were extracted for comparison. Two hundred sixteen patients were included (nal-IRI plus 5-FU/LV/mFFX: 50/166). Patients in the nal-IRI plus 5-FU/LV group were older, had poorer ECOG PS, and a higher rate of peritoneal metastasis than those in the mFFX group. Median overall survival was 9.5 and 9.8months (P=0.97), respectively, and the median progression-free survival was 4.5 vs 4.8months (P=0.61), respectively. Anorexia, fatigue and peripheral neuropathy were more common in the mFFX group, but there was no difference in grade 3/4 adverse events between the two groups. There was no significant difference in efficacy between nal-IRI plus 5-FU/LV and mFFX after GnP. Nal-IRI plus 5-FU/LV appears to be a viable alternative to mFFX as second-line treatment after GnP.

Protocol of a randomized phase II/III study of gemcitabine plus nab-paclitaxel combination therapy versus modified FOLFIRINOX versus S-IROX for metastatic or recurrent pancreatic cancer: JCOG1611 (GENERATE)

Abstract Gemcitabine plus nab-paclitaxel and combination chemotherapy with fluorouracil, leucovorin, irinotecan and oxaliplatin are a standard treatment for metastatic or recurrent pancreatic cancer. Recent studies on metastatic pancreatic cancer have demonstrated promising results of modified fluorouracil, leucovorin, irinotecan and oxaliplatin and S-1, irinotecan and oxaliplatin. A three-arm randomized phase II/III trial has been conducted since April 2019 to confirm the superiority of modified fluorouracil, leucovorin, irinotecan and oxaliplatin and S-1, irinotecan and oxaliplatin over Gemcitabine plus nab-paclitaxel in patients with metastatic or recurrent pancreatic cancer. A total of 732 patients will be enrolled from 42 Japanese institutions within 5 years. The primary endpoint is the response rate in the S-1, irinotecan and oxaliplatin arm for phase II portion and overall survival for phase III portion. The secondary endpoints for phase III portion are progression-free survival, response rate, adverse events, serious adverse events and dose intensity. This trial is registered with the Japan Registry of Clinical Trials [https://jrct.niph.go.jp/], number jRCTs031190009.

Selection of chemotherapy for older patients with pancreatic cancer based on geriatric assessment

There is no established method to select chemotherapy regimens for older patients with unresectable or recurrent pancreatic cancer. In the case of chemotherapy for lung cancer, a phase III study compared regimen selection using geriatric assessment (GA) with conventional regimen selection based on age and performance status and revealed that GA-based regimen selection reduced the number of adverse events experienced without affecting the treatment efficacy [1]. We therefore hypothesized that GA could help to optimize treatment selection for older patients with pancreatic cancer.

Proof of Principle of Combining Fluorescence-Guided Surgery with Photoimmunotherapy to Improve the Outcome of Pancreatic Cancer Therapy in an Orthotopic Mouse Model

BackgroundPancreatic cancer is a recalcitrant disease in which R0 resection is often not achieved owing to difficulty in visualization of the tumor margins and proximity of adjacent vessels. To improve outcomes, we have developed fluorescence-guided surgery (FGS) and photoimmunotherapy (PIT) using a fluorescent tumor-specific antibody.MethodsNude mice received surgical orthotopic implantation (SOI) of the human pancreatic cancer cell line BxPC-3 expressing green fluorescent protein. An anti-carcinoembryonic antigen-related cell adhesion molecule (CEACAM) monoclonal antibody (6G5j) was conjugated to the 700-nm fluorescent dye IR700DyeDX (6G5j-IR700DX). Three weeks after SOI, 16 mice received 50 μg 6G5j-IR700DX via the tail vein 24 h before surgery and were randomized to two groups: FGS-only (n = 8) and FGS + PIT (n = 8). All tumors were imaged with the Pearl Trilogy imaging system and resected under the guidance of the FLARE imaging system. The FGS + PIT group received PIT of the post-surgical bed at an intensity of 150 mW/cm2 for 30 min. Mice were sacrificed 4 weeks after initial surgery, and tumors were imaged with a Dino-Lite digital microscope, excised, and weighed.ResultsThe 6G5j-IR700DX dye illuminated the orthotopic pancreatic tumors for FGS and PIT. The metastatic recurrence rate was 100.0% for FGS-only and 25.0% for FGS + PIT (p = 0.007). The average total recurrent tumor weight was 2370.3 ± 1907.8 mg for FGS-only and 705.5 ± 1200.0 mg for FGS + PIT (p = 0.039).ConclusionsFGS and adjuvant PIT can be combined by using a single antibody–fluorophore conjugate to significantly reduce the frequency of pancreatic cancer recurrence.

Management of afferent loop obstruction using multiple single-pigtail plastic stents in a patient with recurrent metastatic pancreatic cancer.

Malignant afferent loop obstruction (mALO) is defined as duodenal or jejunal mechanical obstruction at the proximal anastomosis site of a gastrojejunostomy associated with locoregional tumor recurrence. As the general condition of patients with tumor recurrence is poor, accurate and rapid diagnosis and minimally invasive treatment are required [1].

High-dose MRI-Guided Adaptive Radiation Therapy for Locally Recurrent Pancreatic Cancer

Introduction: The prognosis of recurrent pancreatic cancer is poor even after curative resection. There have been no reports of MRI-guided radiation therapy for locally recurrent pancreatic cancer after curative resection and chemotherapy. Case Presentation: A 66-year-old man with pancreatic cancer was referred to our institution for local recurrence after failure of surgical resection and second-line chemotherapy. He did not want to undergo further chemotherapy, so high-dose MRI-guided adaptive radiation therapy was performed in daily doses of 2.5 Gy to a total dose of 70 Gy over a period of 5.5 weeks. Three months after radiation therapy, the recurrent tumors disappeared and his CA19-9 level was within normal range without chemotherapy. There were no adverse events during treatment and three months of follow-up. Conclusions: High-dose MRI-guided adaptive radiation therapy may be safe and useful for locally recurrent pancreatic cancer.

Utility of Diffusion-Weighted MRI for Detection of Locally Recurrent Pancreatic Cancer After Surgical Resection.

BACKGROUND. Overlapping imaging findings between local tumor recurrence and postsurgical fibrosis represent a major clinical challenge after pancreatic ductal adeno-carcinoma (PDAC) resection. OBJECTIVE. The purpose of this study was to compare the diagnostic performance of MRI with and without DWI for differentiating locally recurrent tumor and postsurgical fibrosis after PDAC resection. METHODS. This retrospective study included 66 patients (35 men, 31 women; mean age, 60.5 years) who underwent PDAC resection between January 2009 and March 2016, postoperative surveillance CT showing a soft-tissue lesion at the operative site or at the site of peripancreatic vessels, and subsequent MRI with DWI for further evaluation. CT at least 6 months after MRI served as the reference standard, with increase in size of the soft tissue by 5 mm or more differentiating locally recurrent tumor (n = 26) and postsurgical fibrosis (n = 40). Two observers in consensus evaluated MRI characteristics of the soft-tissue lesions. Two additional observers independently reviewed MRI examinations in two separate sessions (conventional MRI alone vs MRI with DWI), recording likelihood of recurrent tumor using a 1-5 scale. ROC analysis was performed, considering scores of 4 or 5 as positive. RESULTS. Subjective diffusion restriction was more common in locally recurrent tumor than postsurgical fibrosis (88.5% vs 25.0%, p = .01). Median ADC was lower for locally recurrent tumor than postsurgical fibrosis (1.3 vs 1.7 × 10-3 mm2/s, p < .001). For both observers, MRI with DWI in comparison with conventional MRI alone showed higher AUC for diagnosis of locally recurrent tumor (observer 1: 0.805 vs 0.707, p = .048; observer 2: 0.898 vs 0.637, p < .001) and higher sensitivity (observer 1: 88.5% vs 61.5%, p = .008; observer 2: 84.6% vs 42.3%, p = .001) but no difference in specificity (observer 1: 72.5% vs 80.0%, p = .08; observer 2, 95.0% vs 85.0%, p = .10). Interobserver agreement was moderate for conventional MRI (κ = 0.41) and good for conventional MRI with DWI (κ = 0.62). CONCLUSION. The addition of DWI to conventional MRI improves the differentiation of locally recurrent tumor and postsurgical fibrosis after PDAC resection, primarily because of improved sensitivity for recurrence. CLINICAL IMPACT. The findings indicate a potential role for MRI with DWI in surveillance protocols after PDAC resection.

High SUVmax on routine pre-operative FDG-PET predicts early recurrence in pancreatic and peri-ampullary cancer.

SUVmax of a primary pancreatic tumour on FDG-PET/CT (SUVmax-p) may predict early post-operative recurrence. This has not been tested in the context of routine pre-operative FDG-PET/CT. It is also unknown whether this association exists independent of local residual tumour. FDG-PET/CT was performed routinely prior to resection of pancreatic or peri-ampullary adenocarcinoma between 2008 and 2012 as part of a previous prospective study. We compared SUVmax-p according to whether recurrence was diagnosed within 6 months of resection. We also determined the odds ratio for recurrence within 6 months for multiple cut-points of SUVmax-p. This analysis was repeated exclusively for patients who had resection with clear surgical margins (R0). Of 56 patients from the initial study 23 underwent resection and were eligible. Recurrence within 6 months was associated with higher median SUVmax-p (5.9 vs 3.5; p=0.04). This was also observed in 12 patients who underwent R0 resection (6.5 vs 2.2; p=0.05). The cut-point with the highest odds for recurrence within 6 months for both groups was SUVmax-p≥5.5 (OR=10.8, CI=1.56-109; OR[R0]=24.0, CI=1.64-1020). SUVmax-p on routine FDG-PET/CT is useful for identifying patients likely to benefit from additional pre-operative staging or neoadjuvant therapy, even where clear margins can confidently be achieved.

An Original Article for Assessment of Multimodality Imaging Based Precise Radiation Therapy (Rt) in the Management of Recurrent Pancreatic Cancers

An Original Article for Assessment of Multimodality Imaging Based Precise Radiation Therapy (Rt) in the Management of Recurrent Pancreatic Cancers

Efficacy of stereotactic body radiation therapy for locoregional recurrent pancreatic cancer after radical resection.

ObjectiveThis study aimed to analyze the efficacy and toxicity of stereotactic body radiotherapy (SBRT) for locoregional recurrent pancreatic cancer after radical resection.MethodsPatients with locoregional recurrent pancreatic cancer after surgery treated with SBRT in our institution were retrospectively investigated from January 2010 to January 2020. Absolute neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) recorded at pretreatment were analyzed. Endpoints included overall survival (OS), progression-free survival (PFS) and cumulative incidences of local failure (LF) and metastatic failure (MF).ResultsA total of 22 patients received SBRT with a median prescribed dose of 40 Gy (range of 30-50 Gy)/4 to 7 fractions. The median OS of all patients was 13.6 months (95% CI, 9.6-17.5 months). 0-1 performance status (HR 12.10, 95% CI 2.04-71.81, P=0.006) and ≤2.1 pre-SBRT NLR (HR 4.05, 95% CI 1.21-13.59, P=0.023) were significant predictors of higher OS on multivariable analysis. The median progression-free survival (PFS) of the cohort was 7.5 months (95% CI, 6.5-8.5 months). The median time to LF and MF were 15.6 months and 6.4 months, respectively. The rate of MF as a first event was higher than that of first event LF. Pain relief was observed in all patients (100%) 6 weeks after SBRT. In terms of acute toxicity, grade 1 including fatigue (6, 27.3%), anorexia (6, 27.3%), nausea (4, 18.2%) and leukopenia (4, 18.2%) was often observed. No acute toxicity of grade 4 or 5 was observed. In terms of late toxicity, no treatment-related toxicity was found during follow-up.ConclusionThis study showed that SBRT can significantly reduce pain, effectively control local tumor progression, and have acceptable toxicity for patients with locoregional recurrence after radical resection of primary pancreatic cancer. Good performance status and lower pre-SBRT NLR were associated with improved overall survival.

Fibrin glue injection method for complex fistula after laparoscopic distal pancreatectomy: a case report

BackgroundPancreatic fistula is the most problematic complication in pancreatectomy. Although drainage can be used to relieve this complication, pancreatic surgeons often encounter refractory pancreatic fistula. Fibrin glue injection, with the use of a twofold diluted solution B and a double-lumen tube, was found effective in treating this complicated pancreatic fistula.Case presentationWe report the case of a 64-year-old Japanese man who underwent laparoscopic distal pancreatectomy for pancreatic tail cancer. After initial drainage of the pancreatic fistula diagnosed 4 days postoperatively, on day 134, refractory pancreatic fistula was observed using contrast-enhanced computed tomography. We used fibrin glue injection, with a twofold diluted solution containing thrombin and calcium chloride and a double-lumen tube, for treating the refractory fistula; the fluid drainage was almost stopped with no fever or abdominal pain. No recurrence of pancreatic cancer has been observed since the procedure.ConclusionsFibrin glue injection was effective for complicated pancreatic fistula after distal pancreatectomy. Using a twofold diluted solution B containing thrombin and calcium chloride and a double-lumen tube makes possible the thorough injection of fibrin glue.

Geriatric nutritional risk index as a prognostic factor in patients with recurrent pancreatic cancer.

The aim of this study is to investigate the prognostic significance of geriatric nutritional risk index (GNRI) at the time of recurrence in patients with recurrent pancreatic cancer, and the relationship between GNRI and skeletal muscle mass for survival outcomes after recurrence. This study enrolled 77 patients who developed postoperative recurrence. The skeletal muscle mass index (SMI) was used in this study. The patients were divided into a high-GNRI group (n = 36) and a low-GNRI group (n = 41) for the GNRI, and were divided into a high-SMI group (n = 38) and a low-SMI group (n = 39) for SMI. The 2-year post-recurrence overall survival of patients in the high-GNRI group was significantly longer than that of patients in the low-GNRI group (P = 0.001). No significant difference for the 2-year post-recurrence OS curves between the high-SMI group and the low-SMI group was observed (P = 0.125). Upon stratifying the patients with high GNRI or low GNRI according to SMI, There was no significant difference in the 2-year post-recurrence OS curves between the patients with both high GNRI and high SMI and the patients with high GNRI and low SMI (P = 0.399). Similarly, There was no significant difference in the 2-year post-recurrence OS curves between the patients with low GNRI and high SMI and the patients with both low GNRI and low SMI (P = 0.256). Multivariate analysis revealed that the GNRI at the time of recurrence was an independent prognostic risk factor in patients with recurrent pancreatic cancer (P = 0.019). The GNRI at the time of recurrence is useful for predicting the prognosis in patients with recurrence pancreatic cancer. Skeletal muscle mass at the time of recurrence is not contributed to predict post-recurrence survival of patients with recurrent pancreatic cancer.

The Diagnostic Performance of 18F-FDG PET/CT in Recurrent Pancreatic Cancer: A Systematic Review and Meta-analysis.

Purpose The CT scan is the best common screening test for pancreatic cancer recurrence after surgery. The goal of our meta-analysis was to assess the diagnostic accuracy of 18F-FDG PET/CT for pancreatic cancer recurrence. Methods We examined PubMed and Embase for suitable papers between 2009 and 2022. The researchers considered studies that looked at the diagnostic usefulness of 18F-FDG PET/CT in identifying local and/or distant disease recurrence throughout the follow-up following pancreatic cancer resection. The Quality Assessment of Diagnostic Performance Studies-2 (QUADAS-2) method was used to evaluate the quality of each study. For each of the publications included, two researchers extracted data independently. The extracted data included general data (authors, year of publication), literature characteristics (country, type of literature, and design of study), characteristics of the patient (patients' number, mean or median age, and treatment regimen), and technical aspects (scanner, injection activity, and image analysis). Results The analysis includes 7 trials with a total of 263 patients. The sensitivity and specificity of 18F-FDG PET/CT in detecting recurrent pancreatic cancer following definitive treatment were 0.89 (95 percent CI: 0.83-0.93) and 0.88 (95 percent CI: 0.72-0.96), respectively, according to the pooled estimates. PET/CT performed well in the diagnosis of recurrent pancreatic cancer, with an AUC of 0.94. (0.91-0.95). Conclusions 18F-FDG PET-CT was found to be a reliable detection method in recurrent pancreatic tumor.

Abstract 3547: IL-12-based cytokine factories modulate tumor microenvironment to eradicate pancreatic tumors in mice and are well tolerated in non-human primates

Abstract Pancreatic cancer is often diagnosed at advanced stages and responds poorly to chemotherapy. Because high tumor T cell infiltration corresponds with better clinical outcomes in pancreatic cancer patients, immunotherapy has gained significant interest over the last decade for the treatment of recurrent pancreatic cancer. IL-12 is a proinflammatory cytokine with pleiotropic effects including activation of CD8+ T cells and NK cells. Unfortunately, systemic high dose IL-12 administration led to severe toxicities in clinical trials which has limited further development of this cytokine as a cancer therapeutic. To address this limitation, we developed an implantable cytokine delivery platform to allow for local administration of IL-12. These cytokine factories, composed of genetically engineered epithelial cells encapsulated in biocompatible polymers, allow for safe and controlled dosing in vivo. Tumor adjacent administration of IL-12-based cytokine factories caused reduction of intraperitoneal pan02 tumor burden by 80% after only 1 week of treatment in mice with pancreatic cancer. Single cell RNAseq of the tumor adjacent immune cells at this time point showed 2x more T and NK cells present in the IL-12 treated mice than untreated mice suggesting modulation of the tumor microenvironment via immune cell infiltration. Importantly, the necessary IL-12 dose was well tolerated in all mice without signs of toxicity for 180 days. In efforts to evaluate the translatability of this platform, we further tested IL-12-based cytokine factories in a non-human primate. The cytokine factories produced a high local IL-12 concentration without substantial leakage into the systemic circulation and were well tolerated by the primates as shown by the lack of fever or weight loss, as well as the lack of renal or liver toxicity. Our findings highlight the therapeutic potential of IL-12 treatments when administered locally via cytokine factories in preclinical animal models. Further, these findings provide rationale for future development and clinical testing of cytokine factories for treatment of a wide range of metastatic peritoneal cancers in humans. Citation Format: Amanda Nash, Samira Aghlara-Fotovat, Bertha Castillo, Annie Nguyen, Andrew Cui, Andrea Hernandez, Peter Rios, Sofia Ghani, Ira Joshi, Chunyu Xu, Rahul Sheth, Weiyi Peng, Jose Oberholzer, Amir Jazaeri, Omid Veiseh. IL-12-based cytokine factories modulate tumor microenvironment to eradicate pancreatic tumors in mice and are well tolerated in non-human primates [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3547.

P-113 A multicenter observational study of liposomal irinotecan and fluorouracil/leucovorin in patients with unresectable or recurrent pancreatic cancer (NAPOLEON-2): Retrospective part

Nanoliposomal irinotecan and fluorouracil with folinic acid (NAL-IRI/FU/LV) is the standard regimen after gemcitabine-based therapy for unresectable or recurrent pancreatic cancer (urPC), based on the results of a phase 3 trial, NAPOLI-1 study. However, the efficacy and toxicity of NAL-IRI/FU/LV in the clinical setting remain unclear. Therefore, we conducted this NAPOLEON-2 study to investigate the clinical features of NAL-IRI/FU/LV and explore the predictive and prognostic factors, both retrospectively and prospectively. Here we show the efficacy and toxicity of NAL-IRI/FU/LV of the retrospective part. This retrospective study collected data from urPC patients treated with NAL-IRI/FU/LV, who had received at least one previous chemotherapy, from 21 hospitals in Japan during the period from June 2020 to May 2021. Patient characteristics, treatment efficacy, and adverse events were analyzed. Overall survival (OS) and progression-free survival (PFS) were estimated by Kaplan-Meier analysis. Incidentally, OS and PFS among the therapeutic lines of NAL-IRI/FU/LV were also analyzed. NAL-IRI/FU/LV was administered to 161 patients. The median follow-up period was 5.3 months (95% confidence interval [95%CI], 4.7–6.3). All patients had previous gemcitabine-based therapy, and NAL-IRI/FU/LV was administered as 2nd/3rd/4th-line chemotherapy to 104/41/16 patients, respectively. Eighteen patients (11%) had received previous irinotecan. The median age was 67 (range, 38–85), and 88 males (55%) were included. Performance Status (PS) was 0/1/2/3 in 46/47/6/1 patients. Nineteen patients (12%) had locally advanced disease and 142 (88%) patients had metastatic disease. Eighty-nine patients (55%) had liver metastasis and 44 patients (27%) had peritoneal metastasis. The median treatment courses were 5 (range, 1–29). The median OS was 9.5 months (95%CI, 7.5–11.0). The median PFS was 3.3 months (95%CI, 2.8–4.4). The overall response rate was 5%, and the disease control rate was 52%. The relative dose intensity was 82.8% in NAL-IRI and 98.2% in FU. The initial dose of NAL-IRI was reduced in 57 patients (35%), mainly because of the uridine diphosphate glucuronosyltransferase (UGT) 1A1 examination status (8%), followed by organ function decrease (6%). Dosage reduction during the treatment (independent from the initial dosage reduction) was conducted in 63 patients (39%), mainly because of neutropenia (14%) and anorexia (10%). More frequent grade 3/4 adverse events (AEs) were neutropenia (23%), anorexia (12%), leukopenia (12%), and anemia (9%). No Grade 5 AE was observed. The median OS in NAL-IRI/FU/LV as 2nd-line therapy compared by as 3rd-line or later regimen was 9.1 vs 10.7 months (hazard ratio [HR], 0.69; 95% CI, 0.42–1.13; p=0.14). The median PFS in NAL-IRI/FU/LV as 2nd-line therapy compared to as 3rd-line or later regimen was 2.9 vs 4.2 months (HR, 0.90; 95% CI, 0.63–1.29; p=0.58). NAL-IRI/FU/LV presented appropriate efficacy compared to previous studies, and the one on OS was shown regardless of therapeutic lines. Toxicity profiles were similar to them and thought to be manageable. In conclusion, NAL-IRI/FU/LV could be a candidate for 2nd-line or later regimen in the real world.