Non-resectable Pancreatic Cancer Research Articles

Early molecular assessment to predict prognosis in patients who respond to chemotherapy on initial imaging in pancreatic cancer.

683 Background: It is helpful to predict early the response to anticancer drugs in non-resectable solid tumors. The purpose of this study is to evaluate whether circulating tumor DNA (ctDNA) helps predict prognosis in patients with non-resectable pancreatic cancer who have received first-line FFX or GnP therapy and have responded to treatment (CR, PR, SD groups) on initial imaging. Methods: A total of 61 patients with non-resectable pancreatic cancer treated with FFX (N=22) and GnP (N=39) as first-line therapy were included in the study. Before and after chemotherapy treatment (median 42 days, after two courses), KRAS-mutated ctDNA was measured using droplet digital PCR with CA19-9. We defined the Responder group as those with CR, PR, or SD other than PD on initial imaging and the molecular assessment as the change in KRAS-mutated ctDNA before and after treatment. (1) No appearance of KRAS-mutated ctDNA before and after treatment was defined as molecular negative (mNT); (2) disappearance of KRAS-mutated ctDNA or decrease in copy number after treatment was defined as molecular response (mR); (3) new appearance of KRAS-mutated ctDNA or increase in copy number after treatment was defined as molecular progressive disease (mPD). We investigated whether the increase or decrease of CA19-9 before and after treatment (Increase group, decrease group) and the molecular assessment were useful as prognostic factors in the Responder group. Results: Male: female = twenty-nine: thirty-two. There were fourteen patients in the locally advanced group and forty-seven patients in the distant metastatic group, both of whom were considered non-resectable. Thirty-eight patients received any second-line treatment. The prognosis of fourteen patients with PD on initial imaging was significantly worse than that of the Responder group (N=47) (Responder: PD=18.4: 9.2 months, p=0.000108). The molecular assessment in the responder group showed 30 patients in mNT group, 10 patients in mR group, and 7 patients in mPD group. The MST was 21.7, 13.2, and 13.2 months. In univariate analysis, increased CA19-9 (Increase group) and mPD were associated with worse prognosis (Increase: Decrease=13.6: 18.4 months, p=0.0487), (mPD: mNT+mR=13.2: 21.7 months, p=0.0194) and the only independent prognostic factor in multivariate analysis was mPD (Hazard ratio=3.005, p=0.0361). Conclusions: The prognosis of patients with molecular negative or molecular response after chemotherapy is relatively good (MST; 21.7 months), and efforts should be made to continue GnP and FFX. In contrast, the prognosis of patients with molecular progressive disease in the responder group is worse. Therefore, strict follow-up and change of anticancer drugs, including palliation, should be considered.

Abstract LB_C05: A novel approach to convert non-resectable pancreatic cancer with major artery involvement using endovascular activation of Padeliporfin by vascular-targeted photodynamic therapy

Abstract Pancreatic cancer is a fatal disease: the patient usually has a very poor prognosis and limited treatment options. It is projected to be the second leading cause of cancer-related death by 2030. It is estimated that 80% of patients have metastatic or localized disease with vascular involvement at presentation, not amenable to surgery. Thus, a therapy that will convert unresectable, due to vascular involvement, tumors to resectable is an unmet medical need. We developed a novel treatment relying on endovascular activation of a photosensitizer Padeliporfin, by a vascular-targeted photodynamic therapy (VTP) to clear the artery from the encasing tumor enabling surgery. Padeliporfin is administered intravenously and activated locally by illumination via an optical fiber, deployed within the tumor encased artery by an angioplasty procedure under fluoroscopy. In a proof-of-concept study in normal swine model, treatment induced areas of ablation in normal pancreatic parenchyma while sparing the artery and other major structures in it’s vicinity. Drug and light doses used were proved effective in other solid tumors in preclinical and clinical studies. Safety was evaluated in a controlled study comprised of 12 pigs subjected to Padeliporfin VTP in a superior mesenteric artery (SMA). Two light doses were tested. Control groups received no drug or no illumination and drug. Follow up was 48 hours or seven days post treatment. Clinical observations and blood test results did not reveal any signs of decreased wellness without differences between treated and control groups. Lipase results were unchanged compared to the baseline. Amylase levels were within the normal range in all animals. Histopathology findings 48 hours post VTP in the SMA and surrounding tissues were similar in treated and control animals. Observed changes were manifested as small lesions consistent with angioplasty procedure impact, involving less than 25% of the media circumference. Small foci of coagulative necrosis were observed in the pancreatic parenchyma in the vicinity of SMA. In the seven-day samples, there was media pressure necrosis in occasional sections of the artery in all groups involving less than 25% of the circumference, attributed to the angioplasty procedure. Minimal fibrosis in a few samples, consisted of focal areas of fibroblast proliferation, indicating early regeneration, with no architectural or thickness changes of the arterial wall. The tissues surrounding SMA as well as organs downstream to the treated artery were mostly within normal ranges. Our results demonstrate that endovascular Padeliporfin VTP is feasible and has an acceptable safety profile together with evidence of ability to ablate pancreatic tumors encasing major abdominal arteries. The efficacy is further supported by our studies showing effective tumor ablations in orthotopic mouse models especially in combination with immune modulating therapies. A phase I trial (NCT5918783) aims to evaluate the potential of this approach for converting unresectable pancreatic cancer patients to amenable for surgery. Citation Format: Dina Preise, Yaniv Cohen, Genia Alpert, Zachary Sacks, Tamar Yechezkel, Natalia Kudinova, Eyal Morag, Ehud Willenz, Julia Rothman, Keren Brook, Inna Krasnopolskaya, Lilach Agemy, Sofia Zilber, Hooman Yarmohammadi, David Kelsen, David Perry, Avigdor Scherz. A novel approach to convert non-resectable pancreatic cancer with major artery involvement using endovascular activation of Padeliporfin by vascular-targeted photodynamic therapy [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr LB_C05.

Radiotherapy for Locally Advanced Pancreatic Adenocarcinoma-A Critical Review of Randomised Trials.

Pancreatic cancer is rising as one of the leading causes of cancer-related death worldwide. Patients often present with advanced disease, limiting curative treatment options and therefore making management of the disease difficult. Systemic chemotherapy has been an established part of the standard treatment in patients with both locally advanced and metastatic pancreatic cancer. In contrast, the use of radiotherapy has no clear defined role in the treatment of these patients. With the evolving imaging and radiation techniques, radiation could become a plausible intervention. In this review, we give an overview over the available data regarding radiotherapy, chemoradiation, and stereotactic body radiation therapy. We performed a systematic search of Embase and the PubMed database, focusing on studies involving locally advanced pancreatic cancer (or non-resectable pancreatic cancer) and radiotherapy without any limitation for the time of publication. We included randomised controlled trials involving patients with locally advanced pancreatic cancer, including radiotherapy, chemoradiation, or stereotactic body radiation therapy. The included articles represented mainly small patient groups and had a high heterogeneity regarding radiation delivery and modality. This review presents conflicting results concerning the addition of radiation and modality in the treatment regimen. Further research is needed to improve outcomes and define the role of radiation therapy in pancreatic cancer.

Treatment of primary or recurrent non-resectable pancreatic cancer with proton beam irradiation combined with gemcitabine-based chemotherapy.

Pancreatic cancer accounts for around 4.6% of cancers deaths worldwide per year. Despite many advances in treatment regimes, the prognosis is still poor. Only 20% of tumors are primarily resectable. Recurrences-both with distant metastasis as well as locoregional-are frequent. For patients with primary nonresectable localized disease or localized recurrences, we offered chemoradiation to achieve local control over along period of time. We here report our results on combined chemoradiation of pancreatic tumors and local recurrences using proton beam therapy. We report on 25patients with localized nonresectable pancreatic cancer (15patients) or local recurrent disease (10patients). All patients were treated with combined proton radiochemotherapy. Overall survival, progression-free survival, local control, and treatment-related toxicity were analyzed using statistically methods. Median RT dose was 54.0 Gy (RBE) for proton irradiation. The toxicity of treatment was acceptable. Four CTCAE gradeIII and IV adverse events (bone marrow disfunction, gastrointestinal [GI] disorders, stent dislocation, myocardial infarction) were recorded during or directly after the end of radiotherapy; two of them were related to combined chemoradiation (bone marrow disfunction, GI disorders). Six weeks after radiotherapy, one additional gradeIV toxicity was reported (ileus, caused by peritoneal carcinomatosis, not treatment related). The median progression-free survival was 5.9months and median overall survival was 11.0months. The pretherapy CA19‑9 level was astatistically significant prognostic factor for enhanced overall survival. Local control at 6months and 12months were determined to be 86% and 80%, respectively. Combined proton chemoradiation leads to high local control rates. Unfortunately, PFS and OS are driven by distant metastasis and were not improved compared to historical data and reports. With this in mind, enhanced chemotherapeutical regimes, in combination with local irradiation, should be evaluated.

A randomized phase II study of full dose gemcitabine versus reduced dose gemcitabine and nab-paclitaxel in vulnerable patients with non-resectable pancreatic cancer (DPCG-01)

BackgroundAccording to current evidence, the best treatment for fit patients with non-resectable pancreatic cancer (PC) is combination chemotherapy, whereas frail patients are recommended gemcitabine (Gem) monotherapy. Randomized controlled trials in colorectal cancer and a post-hoc analysis of gemcitabine and nab-paclitaxel (GemNab) in PC suggest, however, that reduced dose of combination chemotherapy may be feasible and more efficient compared to monotherapy in frail patients. The aim of this study is to investigate whether reduced dose GemNab is superior to full dose Gem in patients with resectable PC, who are not candidates for full dose combination chemotherapy in first line.MethodsThe Danish Pancreas Cancer Group (DPCG)-01 trial is a national multicenter prospective randomized phase II trial. A total of 100 patients in ECOG performance status 0–2 with non-resectable PC, not candidate for full dose combination chemotherapy in first line, but eligible for full dose Gem, will be included. Patients are randomized 1:1 to either full dose Gem or GemNab in 80% of recommended dose.The primary endpoint is progression-free survival. Secondary endpoints are overall survival, overall response rate, quality of life, toxicity and rate of hospitalizations during treatment. The correlation between blood inflammatory markers, including YKL-40 and IL-6, circulating tumor DNA, and tissue biomarkers of resistance to chemotherapy and outcome will be explored. Finally, the study will include measures of frailty (G8, modified G8, and chair-stand-test) to assess whether scoring would enable a personalized allocation to different treatments or indicates a possibility for interventions.DiscussionSingle-drug treatment with Gem has for frail patients with non-resectable PC been the main treatment option for more than thirty years, but the impact on outcome is modest. If improved results and sustained tolerability with reduced dose combination chemotherapy can be shown, this could change the future practice for this increasing group of patients.Trial registrationClinicalTrials.gov Identifier: NCT05841420.Secondary Identifying No: N-20210068.EudraCT No: 2021–005067-52.Protocol version: 1.5, 16-MAY-2023.

Local Ablative Therapy Associated with Immunotherapy in Locally Advanced Pancreatic Cancer: A Solution to Overcome the Double Trouble?-A Comprehensive Review.

Pancreatic ductal adenocarcinoma (PDAC) remains a major killer and is a challenging clinical research issue with abysmal survival due to unsatisfactory therapeutic efficacy. Two major issues thwart the treatment of locally advanced nonresectable pancreatic cancer (LAPC): high micrometastasis rate and surgical inaccessibility. Local ablative therapies induce a systemic antitumor response (i.e., abscopal effect) in addition to local effects. Thus, the incorporation of additional therapies could be key to improving immunotherapy’s clinical efficacy. In this systematic review, we explore recent applications of local ablative therapies combined with immunotherapy to overcome immune resistance in PDAC and discuss future perspectives and challenges. Particularly, we describe four chemoradiation studies and nine reports on irreversible electroporation (IRE). Clinically, IRE is the ablative therapy of choice, utilized in all but two clinical trials, and may create a favorable microenvironment for immunotherapy. Various immunotherapies have been used in combination with IRE, such as NK cell- or γδ T cell-based therapy, as well as immune checkpoint inhibitors. The results of the clinical trials presented in this review and the advancement potential of these therapies to phase II/III trials remain unknown. A multiple treatment approach involving chemotherapy, local ablation, and immunotherapy holds promise in overcoming the double trouble of LAPC.

Direct intraoperative versus percutaneous computed tomographyguided celiac plexus neurolysis in non-resectable pancreatic cancer: A randomized, controlled, non-inferiority study.

Celiac plexus neurolysis (CPN) has been used to control pancreatic cancer (PC) pain, up to our knowledge, there is no study compared intraoperative CPN and computed tomography (CT)-guided techniques. To compare the effects of intraoperative and CT-guided CPN in unresectable PC on pain intensity and analgesic requirements. A total of 90 patients were enrolled in this prospective, randomized, open label, controlled, non-inferiority study, 20 patients were excluded or lost to follow up. The patients were randomly allocated to either intraoperative or CT-guided CPN group. A mixture of 20 mL ethanol 90%, 100 mg lignocaine and 5 mg dexamethasone was infused on each side of the aorta in both groups. Visual analogue score (VAS) and oral daily tramadol consumption were recorded at day 7, 14, 30, 60, 120 and 180 days after intervention. Occurrence of any intervention related complications were reported. Median VAS was similar in both intraoperative and CT-guided CPN groups from day 7 up to 180 days after intervention. The median daily analgesic consumption of oral tramadol (mg) was comparable in both intraoperative and CT-guided CPN groups after intervention at day 7 (50 versus 50), day14 (50 versus 50), day 30 (50 versus 50), day 60 (50 versus 50), day 120 (100 versus 75) and day 180 (100 versus 100). The incidence of diarrhea, vomiting, hypotension and back pain was similar in both groups. Intraoperative CPN is non-inferior to CT-guided CPN as both techniques were similarly associated with reduced pain severity and analgesics requirements.

Deep Learning Improves Pancreatic Cancer Diagnosis Using RNA-Based Variants.

Simple SummaryBlood samples from patients with pancreatic diseases have been analysed to identify predictive RNA-based variants. These variants are not subject to changes in the environment, as is the case for gene expression or metabolic. The variants served together with CA19-9 as input to deep learning for a cohort of 268 patients with pancreatic diseases. Of these patients, 183 patients had pancreatic cancer and 85 from chronic pancreatitis. Among others, we were able to define a set of variants, which were able to differentiate resected pancreatic cancer from chronic pancreatitis with an area under the curve of (AUC) of 96%. Due to the ease of our approach and the wide availability of the used method, it will have a broad impact on the clinical routine. Suspicious patients are only subjected to a blood draw of 2.5 mL blood, and the specimen can then be sent at room temperature to a specialised laboratory.For optimal pancreatic cancer treatment, early and accurate diagnosis is vital. Blood-derived biomarkers and genetic predispositions can contribute to early diagnosis, but they often have limited accuracy or applicability. Here, we seek to exploit the synergy between them by combining the biomarker CA19-9 with RNA-based variants. We use deep sequencing and deep learning to improve differentiating pancreatic cancer and chronic pancreatitis. We obtained samples of nucleated cells found in peripheral blood from 268 patients suffering from resectable, non-resectable pancreatic cancer, and chronic pancreatitis. We sequenced RNA with high coverage and obtained millions of variants. The high-quality variants served as input together with CA19-9 values to deep learning models. Our model achieved an area under the curve (AUC) of 96% in differentiating resectable cancer from pancreatitis using a test cohort. Moreover, we identified variants to estimate survival in resectable cancer. We show that the blood transcriptome harbours variants, which can substantially improve noninvasive clinical diagnosis.

A phase II trial of pharmacological ascorbate, gemcitabine, and nabpaclitaxel for metastatic pancreatic cancer.

TPS791 Background: FOLFIRINOX or gemcitabine/nab-paclitaxel are both frontline chemotherapy options for patients with metastatic pancreas cancer. For most who cannot tolerate the triplet, the latter doublet is the preferred option. Through previous work by our group, pharmacologic ascorbate is known to synergize with gemcitabine; preliminary in vitro data from our group suggests a similar synergistic response with paclitaxel. Though ascorbate has been utilized in cancer therapy, few robust trials have investigated intravenous delivery of ascorbate to deliver plasma concentrations that are cytotoxic to tumor cells. Our prior studies have demonstrated ascorbate induces oxidative stress and cytotoxicity in pancreatic cancer cells; this cytotoxicity appears to be greater in tumor vs. normal cells. We hypothesize that production of hydrogen peroxide mediates the increased susceptibility of pancreatic cancer cells to ascorbate-induced metabolic oxidative stress, resulting in improved treatment outcomes, which has led to the development of the clinical trial (NCT02905578). Methods: All participants receive gemcitabine (1000 mg/m2 weekly) and nab-paclitaxel (125 mg/m2) on cycle days 1, 8, and 15 of a 28-day cycle. Participants are randomized to ± pharmacologic ascorbate (75-gram infusion 3x weekly) in addition to chemotherapy. Study therapy continues until tumor progression. The primary objective is to determine overall survival in patients when treated with combination gemcitabine, nab-Paclitaxel and high-dose ascorbic acid compared to gemcitabine and nab-paclitaxel in patients with non-resectable pancreatic cancer. Secondary objectives include determining objective response rate as well as progression free survival using RECIST 1.1 criteria employing a blinded reviewer for RECIST measurements. The study opened to accrual in 2018 with a goal of enrolling 65 participants. Oversight.Study is conducted under IND 105715 (J. Cullen, sponsor). The University of Iowa Biomedical IRB (IRB-01) serves as the IRB of record. Clinical trial information: NCT02905578.

Acute carcinomatous pancreatitis in patients with pancreatic head cancer complicated by obstructive jaundice

The aim — to improve the diagnostic and surgical palliative treatment results in patients with unresectable pancreatic head cancer, complicated by obstructive jaundice with the canceromatous pancreatitis.Materials and methods. A comparative analysis of the various surgical techniques aimed on the bile duct obstruction syndrome correction by biliodigestive shunting in the palliative surgical treatment of patients with unresectable pancreatic head cancer and mechanical jaundice was done. The analysis of the archival material (1st group, n = 155) was performed at the first stage. It was established that although the pancreatic tumour causes obstruction of both the common bile duct and the main pancreatic duct, however, mechanical jaundice was developed in all patients, and obstructive canceromatous pancreatitis only in 8.8 % of patients. The mild forms of pancreatitis were effectively eliminated by routine methods of intensive care. However, in cases of moderate severe pancreatitis (according to the Atlanta‑92 classification, third revision), the state of patients’ health progressively deteriorated, as the mechanical jaundice background developed a life‑threatening multiorgan failure and the biliodigestive bypassing was not sufficient to avoid a postoperative complications and unsatisfactory results in all cases. Based on the obtained results analysis it was concluded that modernization is need to both surgical tactics and techniques in such patients. Therefore, it was planned and carried out original trial with the optimized treating technology approbation for such patients. To this end, 112 patients with pancreatic head cancer, complicated by mechanical jaundice (Group 2), treated in the surgical department for the period of 2007 — 2018 were included in an open, prospective, randomized study.An approbation of the original algorithm for the carcinomatous pancreatitis verification was performed; the effectiveness evaluation of the proposed tactics and the technique of surgical treatment, including the developed method of combined bilio‑ and pancreaticodigestive bypass surgery was done.Results and discussion. The safety and clinical efficacy of simultaneous with biliodigestive pancreatodigestive bypass was established in patients with locally advanced pancreatic head cancer complicated by obstructive jaundice and carcinomatous pancreatitis. The tactics of a two‑stage surgical treatment was described, which involves first performing external cholangiostomy with minimally invasive techniques or endoscopic transpapillary stenting in patients with signs of liver failure or carcinomatosis pancreatitis, and then the main stage of surgical intervention.Conclusions. The proposed tactics of two‑stage surgical treatment in patients with nonresectable pancreatic head cancer complicated by mechanical jaundice and pancreatic cancer, which includes a two stage technology of surgical interventions with the use of minimally invasive operations in the first stage of treatment and one‑step combined bilio‑ and pancreaticodigestive bypass surgery on the second one, contributes to the reduction of postoperative complications, mortality and improves the patients’ life quality.

Application of Stereotactic Radiation Therapy for Removing Pain Syndrome to Patients with Non-researchable Cancer of Pancreas

Purpose. Control of pain syndrome in patients with locally advanced and recurrent pancreatic cancer using stereotactic radiation therapy (SBRT).
 Materials and methods. Our clinical observations relate to 103 patients with locally advanced (LAPC)and recurrent pancreatic cancer who received radiation therapy in the radiological unit of the NIITs NMI. NN Blokhin "in the periods: 2000-2010. and 2010-2015. The first group consisted of 77 patients with locally advanced non-resectable pancreatic cancer, of which (1a subgroup), 30 patients received radiotherapy in a classical fractionation regimen of 54-60 Gy/5 fraction, 40 patients (1b subgroup) in a mode of hypofractionation. per week 37.5 Gy/5 fraction. Group 2: 26 patients with recurrent pancreatic cancer, including 15 patients (2a subgroup), radiation therapy was performed in the classical fractionation regimen of 54-60 Gy/5 fraction, 11 patients (2b subgroup) underwent a course of radiation therapy in the mode of hypofractionation. Gr 5 times a week 37.5 Gy/5 fraction.
 Results. In SBRT, in 70% of cases, there was a reduction of all types of pain syndrome compared to 37.8% in the control group.
 The conclusion. Stereotactic beam therapy in the mode of hypofractionation is a highly effective, safe method of radiotherapy that effectively reduces pain syndrome in unresectable pancreatic cancer in a short time of treatment in comparison with the traditional method of radiotherapy, which significantly improves the quality of life of this severe category of patients.

Intra-operative ultrasound to determine resecability during surgical exploration of primary non-resectable pancreatic cancer following induction chemotherapy

Intra-operative ultrasound to determine resecability during surgical exploration of primary non-resectable pancreatic cancer following induction chemotherapy

Abstract 4098: New strategy of drug response assessment using PDX organoid platform for non-resectable pancreatic cancer

Abstract To develop an efficient drug screening platform which overcomes the difference of drug response between initial screening and clinical trial stage is a pivotal issue for drug discovery. The patient-derived Xenograft (PDX) model has been reported as a screening system to reflect the microenvironment and heterogeneity of tumor. However, in pancreatic cancer that 80 % of patients is non-resectable, PDX is not be suitable for an initial screening model in terms of economic- and time cost of mouse-based amplification system as well as the lack of obtaining pancreatic tumor tissue from fine needle biopsy or percutaneous gun. To overcome this limitation, here we newly suggested organoids system, miniature organ culture on a dish, that are generated from tumor tissues of orthotopic PDX model, which has the advantages of reflection of each patient's characteristics as well as amplification of limited tumor tissue. Besides, it is possible to screen of drug responsibility with a little number of cells. 12 organoids derived from PDX using needle or gun biopsy tumor tissues showed EpCAM overexpression and each unique morphological phenotype. Moreover, from drug responsibility test, H #43 and H #44, an organoids derived from a gemcitabine-sensitive patients, were highly responsible to gemcitabine, whereas the organoids from gemcitabine-resistant patients, G #20 and H #19 showed a strong resistance to gemcitabine as measuring the IC50 value. In addition, combined treatment with gemcitabine and abraxane to the G #13 model which has no clinical information of drug response due to early death, it inhibited organoid formation significantly, showing a combination index below 1, which was proved through in vivo (PDX) validation. Taken together, the PDX-Organoid system might be able to reflect primary tumor characteristics as well as to overcome the quantitative limitations of the specimen and time cost, and thereby it is possible to predict drug response early in vitro, making it very efficient as an anti-cancer drug development platform for pancreatic cancer. Citation Format: A-Ra Jeon, Sun Il Choi, Sang-Jae Park, Sung-Sik Han, Sun-Young Kong, Min Kyeong Kim, Yu-sun Lee, Jieun Im, Min Kyeong Lee, Sang Hyun Park, Joon-Ki Kim, Kyong-Ah Yoon, Young-Hwan Koh, Ju Hee Lee, Woo Jin Lee, Sang Myung Woo, Yun-Hee Kim. New strategy of drug response assessment using PDX organoid platform for non-resectable pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4098.

Intra-operative ultrasound to determine resectability during surgical exploration of primary non-resectable pancreatic cancer following induction chemotherapy

Intra-operative ultrasound to determine resectability during surgical exploration of primary non-resectable pancreatic cancer following induction chemotherapy

Percutaneous microwave thermosphere ablation of pancreatic tumours.

In oncologic field, thermo-ablative procedures have spread more and more. Percutaneous microwave ablation (MWA) showed same benefits and some advantages over radiofrequency ablation (RFA). To date, a disadvantage of both was the not totally predictable size and shape of ablation volume. The aim of this study was to assess feasibility and safety of MWA in nonresectable pancreatic head cancer using a new technology of MW with high power (100 W) and frequency of 2,450 MH. Five patients with pancreatic head cancer treated with percutaneous MWA under ultrasound guidance were retrospectively reviewed. Mean lesion diameter was 27.8 mm (range, 25-32 mm). Follow-up was performed by CT after 1, 3, 6 and, when possible, 12 months. The shape of the ablation volume was evaluated with multiplanar reformatting (MPR) using roundness index (RI): a value near 1 represents a more spherical ablation zone shape, and a value distant from 1 implies an oval configuration. Ablation and procedure times were registered, together with hospital stay. The feasibility, safety and quality of life (QoL) were reported. The procedure was feasible in all patients (100%). A spherical shape of ablation zone was achieved in all cases (mean RI =0.97). Mean ablation and procedure time were respectively of 2.48 and 28 minutes. Mean hospital stay was 4 days. No major complications were observed. Minor complications resolved during the hospital stay. An improvement in QoL was observed in all patients despite a tendency to return to preoperative levels in the months following the procedure. Percutaneous MWA is a feasible and safe approach for the palliative treatment of advanced stage tumors of the head of the pancreas, despite its complex anatomic relations. The spherical shape of the ablation volume could be related with an improving of the effectiveness and safety.

AB084. P056. Intra-operative ultrasound to determine resectability during surgical exploration of primary non-resectable pancreatic cancer following induction chemotherapy

Background: Determining the resectability of primary non-resectable pancreatic cancer after induction chemotherapy is complicated by under-estimation of tumor regression upon pre-operative imaging. Diagnostic modalities to accurately predict resectability are therefore highly needed. This study describes the initial results of intra-operative ultrasound (IOUS) as diagnostic tool during explorative laparotomy of primary non-resectable pancreatic cancer following induction chemotherapy.

3:27 PM Abstract No. 184 Using FDG PET/CT to predict response to IRE in nonresectable pancreatic cancer: a retrospective analysis of 50 patients

3:27 PM Abstract No. 184 Using FDG PET/CT to predict response to IRE in nonresectable pancreatic cancer: a retrospective analysis of 50 patients

Overall survival in a trial of orally administered CCR2 inhibitor CCX872 in locally advanced/metastatic pancreatic cancer: Correlation with blood monocyte counts.

92 Background: The CCL2-CCR2 signaling axis may facilitate migration of myeloid derived suppressor cells to pancreatic cancer resulting in an immune suppressive tumor microenvironment. CCR2 inhibition in patients with non-metastatic pancreatic cancer was previously reported to decrease tumor-infiltrating macrophages/Treg cells and increase effector T cells (Nywening et al, 2016). Here, a CCR2 specific antagonist CCX872 was used in combination with FOLFIRINOX to treat subjects with locally advanced or metastatic, non-resectable pancreatic cancer in a multi-center study. Methods: Fifty subjects (ECOG score ≤ 2) were enrolled, receiving FOLFIRINOX (fluorouracil [5-FU], leucovorin, irinotecan, oxaliplatin) once every two weeks (maximum 12 cycles) plus 150 mg CCX872 QD or BID for 12 weeks. Subjects showing at least stable disease at the end of the 12-week treatment period were eligible to CCX872 treatment until disease progression. In this ongoing study, all subjects are followed for overall survival (OS). Blood samples were taken at baseline and at intervals throughout the active treatment period for hematologic and flow cytometric analysis of circulating immune cell populations. Results: The all-subjects OS at 18 months is 29%. This compares favorably with previously published data: i.e., OS of only 18.6% at 18 months for FOLFIRINOX regimen alone (Conroy et al, 2011). Peripheral blood monocyte counts at baseline inversely correlate with OS (p = 0.0071, Hazard ratio = 1.169) with CCX872 and FOLFIRINOX combination therapy. Overall, circulating monocytes, inflammatory monocytes and monocytic myeloid derived suppressor cells were reduced by treatment. Conclusions: CCX872-B plus FOLFIRINOX resulted in an OS of 29% at 18 months with no safety issues. Better OS was associated with lower peripheral blood monocyte counts at baseline. Clinical trial information: NCT02345408.

1153P - An observational clinical study with RAS peptide vaccine TG01 evaluating immune response, safety and overall survival in patients with non-resectable pancreatic cancer

1153P - An observational clinical study with RAS peptide vaccine TG01 evaluating immune response, safety and overall survival in patients with non-resectable pancreatic cancer

Preparation and in vitro assessment of wet-spun gemcitabine-loaded polymeric fibers: Towards localized drug delivery for the treatment of pancreatic cancer

Background/ObjectivesThere has been minimal improvement in the prognosis of pancreatic cancer cases in the past 3 decades highlighting the crucial need for more effective therapeutic approaches. A drug delivery system capable of locally delivering high concentrations of chemotherapeutics directly at the site of the tumor is clearly required. The aim of this study was to fabricate and characterize the biophysical properties of gemcitabine-eluting wet-spun polymeric fibers for localized drug delivery applications. Methods/ResultsFibers spun from alginate or chitosan solutions with or without the anticancer drug gemcitabine had a uniform surface area, were internally homogeneous and ranged from 50-120 μm in diameter. Drug encapsulation ranged from 13-52%, depending on the type and concentration of polymer used. Gemcitabine displayed first-order release kinetics where 64–82% of the loaded drug was rapidly released within the first 10 h followed by a sustained release over the next 134 h. A time dependent inhibition of ex vivo tumor spheroid growth and cell viability was observed after incubation with gemcitabine-loaded fibers but not control fibers. ConclusionWith further development these studies could lead to the manufacture of a safe and effective delivery system designed to combat non-resectable pancreatic cancer for which currently there is minimal chance of cure.