Treatment Of Unresectable Pancreatic Cancer Research Articles

Feasibility and safety of endoscopic ultrasound-guided diffusing alpha emitter radiation therapy for advanced pancreatic cancer: Preliminary data

Background and study aims: Pancreatic cancer is a devastating disease with limited locoregional treatment options. Diffusing alpha-emitter radiation therapy (Alpha DaRT), a novel cancer treatment using alpha-particle interstitial radiotherapy, may help address this challenge. The aim of this study was to evaluate the feasibility and safety of endoscopic ultrasound (EUS)-guided Alpha DaRT for advanced pancreatic cancer. Patients and methods: Patients with inoperable locally advanced or metastatic pancreatic adenocarcinoma were treated with EUS-guided Alpha DaRT insertion. The Alpha DaRT sources were delivered into pancreatic tumors using a standard EUS needle with a novel proprietary applicator. Adverse events (AEs) were assessed based on the Common Terminology Criteria for Adverse Events version 5.0. Tumor response was evaluated by imaging 4 to 6 weeks post treatment. Results: The first five patients were treated between March and September 2023. The procedure was technically successful in all cases, with Alpha DaRT sources inserted into the target tumor. Estimated gross tumor volume coverage ranged from 8% to 44%. Fourteen AEs were reported among three patients. Four were serious AEs, none of which was associated with the treatment, but rather, with disease progression or medical assistance in dying. Only two AEs (mild) were deemed possibly related to the study device. At the 35-day visit, two patients had progressive disease and three had stable disease, with one of the latter showing partial response 2 months post procedure. Conclusions: Preliminary results from this first-in-human trial indicate that EUS-guided Alpha DaRT treatment for unresectable pancreatic cancer is feasible and safe, with no device-associated serious AEs. Further investigation of this promising novel modality is underway.

Nanoliposomal irinotecan with fluorouracil and folinic acid, FOLFIRINOX, and S-1 as second-line treatment for unresectable pancreatic cancer after gemcitabine/nab-paclitaxel

This study aimed to compare second-line treatment outcomes for patients with unresectable pancreatic cancer previously treated with gemcitabine plus nab–paclitaxel (GnP) therapy. We conducted an integrated analysis of two retrospective studies included 318 patients receiving nanoliposomal irinotecan + 5-fluorouracil/folinic acid (NFF) (n = 102), S-1 (n = 57), or FOLFIRINOX (n = 14) as second-line treatment. Median overall survival (OS) in the NFF group was 9.08 months, significantly better than S-1 (4.90 months, P = 0.002). FOLFIRINOX had a median OS of 4.77 months, not statistically different from NFF. Subgroup analyses of OS indicated NFF was generally superior, however, a statistical interaction was observed between the treatment regimen in serum Alb < 3.5 g/dL (P = 0.042) and serum CRP ≥ 0.3 mg/dL (P = 0.006). Median progression-free survival (PFS) was 2.93 months for NFF, significantly better than S-1 (2.53 months, P = 0.024), while FOLFIRINOX had a comparable PFS (3.04 months, P = 0.948). Multivariate analysis identified the serum CRP, serum CA19-9, duration of first-line GnP therapy, and use (yes/no) of S-1 for second-line treatment as independent predictors for OS. This study concludes that second-line NFF therapy demonstrated a more favorable OS compared to S-1 therapy, however, it is still important to consider the patient background characteristics while selecting the most appropriate treatment.

Prognostic factors for GEM + nab-PTX combination therapy in elderly patients with pancreatic cancer.

678 Background: Japanese Clinical Practice Guidelines for Pancreatic Cancer 2022 recommends gemcitabine (GEM) + nab-paclitaxel (nab-PTX) therapy (GnP regimen) as the first line chemotherapy for elderly patients with pancreatic cancer. In Japan, it is reported that about 69% of pancreatic cancer patients are elderly, and Only few group reported the safety of GnP regimen. In this study, we investigated the anti-tumor efficacy and prognostic factors of GnP regimen in patients with pancreatic cancer at our hospital, with a particular focus on age. Methods: 160 patients who started GnP therapy as the first line treatment for unresectable pancreatic cancer between February 2016 and December 2021 were included in the study. 70 years of age or older was defined as elderly, and patient background and treatment efficacy were compared in two groups: non-elderly patients (n=84) and elderly patients (n=76). Prognostic factors were also compared between the overall population and the elderly. Results: Patients with a primary lesion in the pancreatic head were 32 (38.1%) of the non-elderly patients and 35 (46.1%) of the elderly patients. 60 patients (71.4%) of the non-elderly and 38 (50.0%) of the elderly had distant metastases. The median overall survival was 16.0 months for the non-elderly and 17.7 months for the elderly, with no significant difference (p=0.93). Significant prognostic factors for the overall subject population were ECOG PS (HR 1.80, p=0.019), liver metastasis (HR 2.36, p&lt;0.01), CRP (HR 1.91, p&lt;0.01) and NLR (HR 2.65, p&lt;0.01). The only significant prognostic factor in the elderly was liver metastasis (HR 2.59, p&lt;0.01). Conclusions: GnP regimen in pancreatic cancer can be expected to have the same antitumor effect in elderly patients as in non-elderly patients. However, significant prognostic factors were reduced in the elderly, we need to identify specific factors to determine the indication for treatment in the elderly patients.

Advances in the Treatment of Unresectable Pancreatic Cancer

Advances in the Treatment of Unresectable Pancreatic Cancer

Conventionally Fractionated vs. Hypofractionated Radiotherapy for Treatment of Unresectable Pancreatic Cancer: Local Control and Survival Outcomes in a Retrospective Single-Institutional Analysis

Unresectable pancreatic cancer (UPC) is associated with dismal survival outcomes, with a reported median survival of 8-12 months. The role of radiotherapy (RT) and the choice of optimal fractionation remains unclear. Our objective was analyzing the outcomes associated with local radiotherapy as well as determine the best radiotherapeutic approach to treat these patients. From a database of 209 radiation plans of patients treated for pancreatic cancer in a single institution between August 2007 to August 2021, patients with UPC were selected for this REB approved retrospective study. From the 209 plans, 136 unique patients were identified who had RT for UPC. The mean age of the cohort was 67.6 years, 10% were >80 years and 37% were female. Median follow-up was 9.3 months. 54 patients had distant metastases at the time of RT and were analyzed separately. Outcomes where analyzed based on whether patients received Conventionally fractionated RT (CFRT) (defined as >15 fractions) (n = 23 (17%)), Hypofractionated RT (HypoRT) (defined as ≤15 fractions and EQD2<40Gy for α/β = 3) (n = 40 (29%)) and those treated with Stereotactic Body RT (SBRT) (defined as ≤5 fractions and EQD2≥40Gy for α/β = 3) (n = 19 (14%)). The mean overall survival (OS) and freedom from progression (FFP) in the SBRT cohort was 17.2 and 7.4 months respectively, in the CFRT cohort was 22.6 and 9.9 months respectively and in the HypoRT cohort was 11.4 and 4.9 months respectively. All CFRT patients received chemotherapy. Mean OS was drastically lower in SBRT and HypoRT patients who did not receive any chemotherapy (11.9 and 3.4 months respectively). Patients with metastatic disease at presentation and receiving HypoRT had mean OS of 13.4 months. The average EQD2 for the cohorts were 45.4 Gy, 49.2 Gy and 30.3 Gy for CFRT, SBRT and HypoRT respectively. Our study demonstrates that CFRT with concurrent chemotherapy offers better therapeutic outcomes in patients with UPC compared to HypoRT. The role of dose escalated SBRT needs to be explored as an equal alternative.

327 Conventionally Fractionated Versus Hypofractionated Radiotherapy for Treatment of Unresectable Pancreatic Cancer: Local Control and Survival Outcomes in a Retrospective Single-Institutional Analysis

327 Conventionally Fractionated Versus Hypofractionated Radiotherapy for Treatment of Unresectable Pancreatic Cancer: Local Control and Survival Outcomes in a Retrospective Single-Institutional Analysis

Clinical Impact of Nutrition and Inflammation Assessment Tools in Pancreatic Cancer Treatment.

Perioperative adjuvant treatment and complete resection is the standard treatment for resectable pancreatic cancer and systemic chemotherapy is standard treatment for unresectable pancreatic cancer. To improve the survival of patients with pancreatic cancer, it is necessary to identify promising biomarkers to optimize the treatment. The availability of biomarkers may allow patients to receive a more aggressive or less toxic treatment. Recent studies showed that the inflammatory and nutritional status perioperatively and/or during chemotherapy affect short and long-term oncological outcomes in pancreatic cancer. Introduction of inflammatory and nutritional status evaluation in pancreatic cancer treatment might improve the postoperative surgical complications or chemotherapy-induced adverse events. However, to introduce these various nutritional and inflammation assessment tools in daily clinical practice, it is necessary to understand the characteristics of each nutrition and inflammation assessment tool. This review summarizes the background, current status, and future perspectives of nutrition and inflammation assessment tools in pancreatic cancer treatment.

Combination of chemotherapy and focused ultrasound for the treatment of unresectable pancreatic cancer: a proof-of-concept study.

To investigate the safety and preliminary efficacy of the combined treatment of focused ultrasound (FUS) and chemotherapy (nab-paclitaxel plus gemcitabine, nPac/Gem) for patients with unresectable pancreatic cancer. Patients pathologically diagnosed with unresectable pancreatic cancer were included. Low (Isppa = 1.5 kW/cm2), intermediate (2.0 kW/cm2), and high (2.5 kW/cm2) FUS intensity treatment groups were predefined. A 1% duty cycle and the 3+3 scheme were used. Six combined treatments were performed, and adverse events were assessed. Changes in tumor size and tumor response, CA 19-9 level, and patient-reported outcomes at the immediate follow-up (F/U) and/or at the 3-month F/U and survival were evaluated. Three participants were enrolled in each intensity group. No adverse device effect or dose-limiting toxicity occurred in any of the participants. Seven of the nine participants experienced a >15% tumor size decrease at the immediate F/U CT and at the 3-month F/U CT. The CA 19-9 level decreased in all of the participants at the immediate F/U. All participants in the intermediate-intensity treatment group showed a > 30% tumor size decrease, partial response, and a significant decrease in the CA 19-9 level at 3-month F/U and longer survival (p < 0.05). FUS with an intensity of 1.5 to 2.5 kW/cm2 was safe in the combined treatment of FUS and nPac/Gem. Considering the results of the change in tumor size, the change in CA 19-9 level, tumor response, and survival, these FUS parameters can be used for subsequent clinical trials. • No adverse device effect or dose-limiting toxicity occurred in any of the participants when focused ultrasound with an intensity of 1.5-2.5 kW/cm2 and a low duty cycle of 1% was combined with chemotherapy. • The intermediate-intensity group showed a >30% tumor size decrease, partial response, and a significant decrease in CA 19-9 in all of the participants at the 3-month follow-up and the longest survival. • Any focused ultrasound setting used in this study could be safe and optimal for subsequent clinical trials.

Comparing the Efficacy and Safety of Gemcitabine plus Nab-Paclitaxel versus Gemcitabine Alone in Older Adults with Unresectable Pancreatic Cancer.

BackgroundGemcitabine plus nab-paclitaxel (GnP) has been a standard treatment for unresectable pancreatic cancer (uPC); however, the current treatment status and usefulness in older adults with uPC remain unclear. Therefore, we aimed to investigate the patient background and compare the efficacy and safety of GnP versus other treatments in older adults with uPC.Patients and MethodsIn this prospective observational study, we enrolled 233 eligible patients aged ≥76 years with pathologically proven, clinically uPC, and no history of chemotherapy from 55 Japanese centers during September 2018-September 2019. The main endpoints were overall survival (OS), progression-free survival (PFS), and safety. Geriatric assessments were performed upon registration and after 3 months. To adjust for confounders, we conducted propensity score-matched analyses.ResultsGnP, gemcitabine alone (Gem), best supportive care, and other therapies were administered to 116, 72, 16, and 29 patients, respectively. In the propensity score-matched analysis, 42 patients each were selected from the GnP and Gem groups. The median OS was longer in the GnP group than in the Gem group (12.2 vs. 9.4 months; hazard ratio [HR], 0.65; 95% CI, 0.37-1.13). The median PFS was significantly longer in the GnP group than in the Gem group (9.2 vs. 3.7 months; HR, 0.38; 95% CI, 0.23-0.64). The incidence of severe adverse events was higher with GnP than with Gem; however, the difference was not significant.ConclusionGnP is more efficacious than Gem in patients aged ≥76 years with uPC despite demonstrating a higher incidence of severe adverse events.

Application and Research Status of &amp;lt;sup&amp;gt;125&amp;lt;/sup&amp;gt;I Seeds Brachytherapy in Unresectable Pancreatic Cancer

Pancreatic cancer is a digestive system tumor with high degree of malignancy. At present, systemic chemotherapy is the main treatment method. However, due to the difficulty in early diagnosis and easy spread of pancreatic cancer, the survival cycle of patients is short and the treatment effect is poor. ¹²⁵I seed brachytherapy has obvious advantages in the treatment of malignant tumors, and has been widely used in the treatment of unresectable pancreatic cancer. Either used alone or combined with chemotherapy, the treatment of ¹²⁵I seed brachytherapy can effectively relieve pain, improve life quality and prolong survival. However, there are few reports about the application status. This article reviews the current updates of ¹²⁵I seed brachytherapy for resectable pancreatic cancer, and expounds the application status of ¹²⁵I seeds brachytherapy in combination with monotherapy chemotherapy, dual drug chemotherapy, targeted therapy, immunity therapy, palliative surgery, external radiotherapy and traditional Chinese medicine. Based on the retrospective review, future directions of research and development of brachytherapy for unresectable pancreatic cancer is also proposed, to provide better treatment care for pancreatic cancer patients. At present, there are still many problems to be solved, such as formulating the principles and standards for the application of radioactive particle implantation in the comprehensive treatment of pancreatic cancer; We will continue to standardize and optimize the operation process and distribution means of radioactive seed implantation technology, and better promote 125I radioactive seed implantation technology.

Modified FOLFIRINOX versus sequential chemotherapy (FOLFIRI/FOLFOX) as a second-line treatment regimen for unresectable pancreatic cancer: A real-world analysis.

BackgroundAlthough second‐line treatment for pancreatic cancer has been proven to have survival benefit, it is not clear which is the most preferred regimen. This study compared the efficacy and safety of modified FOLFIRINOX (mFOLFIRINOX) and sequential chemotherapy (FOLFIRI/FOLFOX) as a second‐line treatment regimen for unresectable pancreatic cancer.MethodThis was a retrospective single‐center analysis of all patients who initiated treatment with mFOLFIRINOX or sequential chemotherapy from December 2014 to May 2019 as a second‐line treatment for unresectable pancreatic cancer. The sequential chemotherapy group included all patients who initiated sequential chemotherapy. For efficacy analysis, the primary endpoint was overall survival (OS) of all patients, excluding those with locally advanced pancreatic cancer. For safety analysis, we assessed the incidence of grade ≥3 adverse events in all patients.ResultsSeventy‐four patients (mFOLFIRINOX group, n = 44; sequential chemotherapy group, n = 30) were included. OS tended to be slightly prolonged in the mFOLFIRINOX group than in the sequential chemotherapy group (median 10.6 [95% confidence interval {CI} 5.9–13.8] vs. 8.5 [95% CI 5.0–12.2] months; hazard ratio 1.40 [95% CI 0.71–2.71]). The objective response rate and disease control rate were 8.1% and 64.9%, respectively, in the mFOLFIRINOX group and 3.8% and 42.3%, respectively, in the sequential chemotherapy group. In safety analysis, the grade ≥3 rates of neutropenia, febrile neutropenia, and anorexia were 40.9%, 6.8%, and 18.2%, respectively, in the mFOLFIRINOX group and 3.3%, 0%, and 3.3%, respectively, in the sequential chemotherapy group.ConclusionsWhereas efficacy tended to be slightly better in the mFOLFIRINOX group than in the sequential chemotherapy group, given the higher incidence of grade ≥3 adverse events with mFOLFIRINOX than with sequential chemotherapy, sequential chemotherapy is a regimen with better risk–benefit balance than mFOLFIRINOX, and can be considered a second‐line treatment option for patients with unresectable pancreatic cancer.

Meta-Analysis of Definitive Photon and Particle Irradiation for Locally Advanced Pancreatic Cancer

The optimal treatment for unresectable pancreatic cancer remains unclear, as patients with locally advanced pancreatic cancer (LAPC) have poor outcomes despite aggressive therapies. Due to these poor outcomes, there has been interest in advanced techniques for definitive radiation, and robust literature has emerged for the definitive irradiation of LAPC, including photon-based techniques such as SBRT and IMRT/VMAT, proton, and carbon-ion irradiation. Despite promising early results, there are few advanced-stage clinical trials comparing these modalities.A systematic review was performed in December 2020 on PubMed/Medline using the following search terms: "pancreas" and "carbon ion radiotherapy," "proton," "stereotactic body radiation therapy," "SBRT," "IMRT," or "VMAT," which yielded 860 results. Retrospective or prospective studies using either SBRT, IMRT, VMAT, proton, or carbon ion radiotherapy for definitive radiation with or without concurrent chemotherapy were included. Resectable/borderline resectable, adjuvant radiation, and trials using older radiation techniques (3D conformal, 2D planning) were excluded from analysis. The primary outcomes were grade 3-5 acute and late toxicity, with secondary outcomes including 1-year overall survival (OS) and 1-year local control (LC). Random effects meta-analyses were conducted for each primary and secondary outcome using the restricted maximum likelihood method. The Wald-type test was used to compare treatment modalities, where the null hypothesis was rejected for P < 0.05.A total of 6 particle studies (proton and carbon ion) and 11 photon studies (IMRT/VMAT and SBRT) were included in the final analysis. The summary effect size for acute grade 3-5 toxicity was 4.9% for photon irradiation compared to 2.7% with particles (P = 0.46). The summary effect size for late grade 3-5 toxicities were 3.7% and 1.0% for photons and particles, respectively (P = 0.13). At 1 year, LC was 71.6% with photons and 86.7% with particles (P = 0.07), with OS of 59.3% and 74.4%, respectively (P = 0.09).Particle therapy with protons or carbon appears to be at least equally efficacious and safe compared to advanced photon-based treatment techniques in the treatment of unresectable pancreatic cancer. These findings are hypothesis generating and should be validated in well-designed prospective trials.

Guidelines for the diagnosis and treatment of pancreatic cancer in China(2021)

The incidence of pancreatic cancer has been rising worldwide,while its clinical diagnosis and treatment remain a great challenge. To present the update and improvements in the clinical diagnosis and treatment of pancreatic cancer in recent years, Chinese Pancreatic Surgery Association,Chinese Society of Surgery,Chinese Medical Association updated "Guidelines for the diagnosis and treatment of pancreatic cancer in China （2021）" based on the Guideline of Management of Pancreatic Cancer in China which had been published in 2014. This updated guideline was formulated after reviewing evidence-based and problem-oriented literatures published from 2015-2021,mainly focusing on highlight issues regarding diagnosis and surgical treatment of pancreatic cancer,conversion strategies for locally advanced pancreatic cancer,treatment of pancreatic cancer with oligo metastasis,adjuvant and neoadjuvant therapy,standardized processing of surgical specimens and evaluation of surgical margin status,systemic treatment for unresectable pancreatic cancer,genetic testing,as well as postoperative follow up of patients with pancreatic cancer. Forty recommendation items were finally proposed based on the above issues,and the quality of evidence and strength of recommendations were graded using the Grades of Recommendation,Assessment,Development,and Evaluation system. This guideline aims to improve the ability of clinical diagnosis and therapy,especially surgical treatment of pancreatic cancer in China,and furtherly improve the prognosis of pancreatic cancer patients.

Guidelines for the diagnosis and treatment of pancreatic cancer in China (2021)

Abstract The incidence of pancreatic cancer has been rising worldwide, and its clinical diagnosis and treatment remain a great challenge. To present the update and improvements in the clinical diagnosis and treatment of pancreatic cancer in recent years, Chinese Pancreatic Association, the Chinese Society of Surgery, Chinese Medical Association revised the Guidelines for the Diagnosis and Treatment of Pancreatic Cancer in China (2014) after reviewing evidence-based and problem-oriented literature published during 2015–2021, mainly focusing on highlight issues regarding diagnosis and surgical treatment of pancreatic cancer, conversion strategies for locally advanced pancreatic cancer, treatment of pancreatic cancer with oligo metastasis, adjuvant and neoadjuvant therapy, standardized processing of surgical specimens and evaluation of surgical margin status, systemic treatment for unresectable pancreatic cancer, genetic testing, as well as postoperative follow up of patients with pancreatic cancer. Forty recommendation items were finally proposed based on the above issues, and the quality of evidence and strength of recommendations were graded using the Grades of Recommendation, Assessment, Development, and Evaluation system. This guideline aims to standardize the clinical diagnosis and therapy, especially surgical treatment of pancreatic cancer in China, and further improve the prognosis of patients with pancreatic cancer.

A Single Institution Experience On High Dose MRI-Guided Stereotactic Body Radiotherapy For Pancreatic Cancer: Early Outcomes, Safety And Feasibility

Accumulating evidence has shown a benefit for dose-escalation and stereotactic body radiotherapy (SBRT) in the treatment of unresectable pancreatic cancer. To this end, MR-guided radiotherapy (MRgRT) allows for reduction of dose to organs at risk while accounting for intra- and inter-fraction motion with online treatment plan adaptation to improve target coverage. We sought to report on our early experience in MRgSBRT for pancreatic cancer. This study was a retrospective cohort of biopsy-proven, pancreatic cancer patients that were recommended to undergo high biological equivalent dose (BED) SBRT to their primary disease and were treated on the MR-Linac in 5 fractions. Acute toxicity measured by Common Terminology Criteria for Adverse Events (v5) by a provider during the weekly on-treatment visit, at 1 month following completion of treatment, and at regular 3-month follow-up intervals thereafter. Toxicity occurring greater than 3 months after completion of radiotherapy was deemed late. From April, 2019 until January, 2020 a total of 35 consecutively treated patients (48% borderline resectable, 37% locally advanced; 80% cN0) with a median follow up from diagnosis of 8.3 months were treated to median 45 Gy (Range: 35-50 Gy) on our MRI-Linac. At least three months of induction chemotherapy was given in 88.5% of patients, most commonly FOLFIRINOX (71%) or gemcitabine/abraxane (26%). Twenty-three patients (66%) were treated with online adaptive planning and 4 patients (11%) were treated for locally recurrent, unresectable disease with history of prior radiotherapy (n = 3 prior adjuvant chemoradiation, n = 1 prior definitive SBRT in the lateral decubitus position). Overall, nine patients (25%) experienced any toxicity, predominantly grade 1 fatigue (55%) and nausea (44%). A single patient (2.8%) experienced grade 3 abdominal pain 1.5 weeks after completion of SBRT presumed to be duodenitis from CT imaging. No grade 4/5 or any late toxicity from SBRT has been observed in this cohort to date. At the time of analysis, 9 patients (55% borderline resectable, 22% locally advanced) successfully underwent resection of their primary tumor (100% R0 resection) without perioperative mortality and with 2 reported pathological complete response (TRG 0; 22%), 2 patients with TRG 1 response and 5 patients with TRG 2 response (55%). Overall, no patients had experienced local recurrence based on CT pancreas protocol RECIST criteria and eight patients (22.8%) had distant progression with one reported death (OS: 97%). MRgSBRT for pancreatic cancer appears to be well-tolerated with encouraging early local control and without significant morbidity or increased perioperative mortality. Adaptive treatment parameters and tissue constraints for adaptive and non-adaptive treatment plans minimize toxicity for this increasingly utilized treatment.

Therapeutic effect and safety of individualized chemotherapy combined with sequential immunotherapy based on BRCA1 mRNA expression level in the treatment of unresectable pancreatic cancer.

e16773 Background: Pancreatic cancer is a kind of digestive tumor with low incidence but high degree of malignancy. It is characterized by difficult in early detection and invasive metastasis. Together with high recurrence and metastasis rate after resection, the prognosis of pancreatic cancer is extremely poor. To explore the role of BRCA1 mRNA expression in the chemotherapy of unresectable pancreatic cancer and the synergistic effect of chemotherapy and immunotherapy, our center has carried out a clinical trial which focuses on individualized chemotherapy combined with sequential immunotherapy according to BRCA1 mRNA expression in the first-line treatment of unresectable pancreatic cancer. Methods: The expression of BRCA1 mRNA in tumor tissues of patients with pancreatic cancer was detected. According to the expression level, gemcitabine combined with nab-paclitaxel-based or gemcitabine combined with oxaliplatin-based biweekly chemotherapy combined with sequential GM-CSF and IL-2 immunotherapy was applied. Patients’ conditions and the efficacy and safety were assessed every 4 cycles. Results: A total of 25 patients were enrolled in the study. All of them were observed for toxic side effects and 24 of them were evaluated for efficacy. The median overall survival and median progression-free survival were 11.9 months and 6.3 months. The disease control rate was 91.7%, of which 37.5% (9/24) patients achieved partial remission (PR), 54.2% (13/24) patients achieved stable disease (SD) and 8.3% (2/24) patients were assessed as progressive disease(PD). Of the 15 patients with medium or high expression in BRCA1 mRNA, 7 achieved PR and 8 achieved SD. Of the 9 patients with low BRCA1 mRNA expression, 2 achieved PR, 5 achieved SD and 2 had PD. The proportion of eosinophils in the blood of some patients with good therapeutic effects was significantly higher than that before treatment. Hematological and non-hematological toxicity during the treatment were mostly grade 1~2. The two most common grade 3~4 adverse events were fever and thrombocytopenia. Conclusions: Our results suggest that individualized selection of chemotherapy combined with sequential immunotherapy according to BRCA1 mRNA expression level in the treatment of unresectable pancreatic cancer have curative effect and controllable adverse reactions. The improvement of treatment efficiency may be related to the activation of non-specific immune response.

Gemcitabine, Nab-Paclitaxel, and Bosentan for the Treatment of Unresectable Pancreatic Cancer

Gemcitabine, Nab-Paclitaxel, and Bosentan for the Treatment of Unresectable Pancreatic Cancer

704P - Results from phase I study of the oncolytic viral immunotherapy agent Canerpaturev (C-REV) in combination with gemcitabine plus nab-paclitaxel as first-line treatment of unresectable pancreatic cancer

704P - Results from phase I study of the oncolytic viral immunotherapy agent Canerpaturev (C-REV) in combination with gemcitabine plus nab-paclitaxel as first-line treatment of unresectable pancreatic cancer

Fasting Reduces Intestinal Radiotoxicity, Enabling Dose-Escalated Radiation Therapy for Pancreatic Cancer

Chemotherapy combined with radiation therapy is the most commonly used approach for treating locally advanced pancreatic cancer. The use of curative doses of radiation in this disease setting is constrained because of the close proximity of the head of the pancreas to the duodenum. The purpose of this study was to determine whether fasting protects the duodenum from high-dose radiation, thereby enabling dose escalation for efficient killing of pancreatic tumor cells. C57BL/6J mice were either fed or fasted for 24 hours and then exposed to total abdominal radiation at 11.5 Gy. Food intake, body weight, overall health, and survival were monitored. Small intestines were harvested at various time points after radiation, and villi length, crypt depth, and number of crypts per millimeter of intestine were determined. Immunohistochemistry was performed to assess apoptosis and double-strand DNA breaks, and microcolony assays were performed to determine intestinal stem cell regeneration capacity. A syngeneic KPC model of pancreatic cancer was used to determine the effects of fasting on the radiation responses of both pancreatic cancer and host intestinal tissues. We demonstrated that a 24-hour fast in mice improved intestinal stem cell regeneration, as revealed by microcolony assay, and improved host survival of lethal doses of total abdominal irradiation compared with fed controls. Fasting also improved survival of mice with orthotopic pancreatic tumors subjected to lethal abdominal radiation compared with controls with free access to food. Furthermore, fasting did not affect tumor cell killing by radiation therapy and enhanced γ-H2AX staining after radiation therapy, suggesting an additional mild radiosensitizing effect. These results establish proof of concept for fasting as a dose-escalation strategy, enabling ablative radiation in the treatment of unresectable pancreatic cancer.

Palliative therapy in pancreatic cancer—palliative surgery

Pancreatic cancer is a highly lethal disease with a dismal prognosis. It will probably become the second leading cause of cancer-related death within the next decade in Western countries. Over 80% of patients undergo palliative treatment for unresectable pancreatic cancer due to locally advanced disease or metastases. Those patients often develop gastric outlet obstruction (GOO), obstructive jaundice and pain during the course of their disease. Symptoms such as vomiting, anorexia, pruritus and jaundice will impact the quality of life (QOL) and could delay the administration of the chemotherapy. Palliative therapy in pancreatic cancer aims to relieve the symptoms durably and to improve the QOL. Palliative surgery was traditionally considered as a gold standard with the "double by-pass" including biliary-digestive and gastro-jejunal anastomosis. However, since the development of endoscopic stenting and minimally invasive surgery, the choice of the best modalities remains debated. While there is still a place for surgical gastrojejunostomy (GJ) in case of duodenal or GOO, endoscopic biliary stenting during endoscopic retrograde cholangiopancreatography (ERCP) is now accepted as the gold standard in case of obstructive jaundice. In pain management, endoscopic ultrasound guided or percutaneous celiac plexus neurolysis is recommended. The selection of the best technique should consider the effectiveness and the morbidity of the treatment, the performance status of the patient and the disease stage. While endoscopic stenting is associated with earlier recovery and shorter length of stay, recurrence of symptoms and reintervention are less frequent after palliative surgery. Finally, controversy exists on whether to perform prophylactic palliative surgery in the absence of symptoms when unresectable disease is discovered during surgical exploration.