Unresectable Pancreatic Cancer Research Articles

152P Interim analysis of the NAPOLEON-2 study: Safety evaluation of nanoliposomal irinotecan with fluorouracil and folinic acid for unresectable pancreatic cancer patients with prior biliary drainage

152P Interim analysis of the NAPOLEON-2 study: Safety evaluation of nanoliposomal irinotecan with fluorouracil and folinic acid for unresectable pancreatic cancer patients with prior biliary drainage

Palliative radiotherapy for tumor bleeding in patients with unresectable pancreatic cancer: a single-center retrospective study

BackgroundPatients with unresectable pancreatic cancer (PC) sometimes experience gastrointestinal bleeding (GIB) due to tumor invasion of the gastrointestinal tract (tumor bleeding); no standard treatment has been established yet for this complication. Palliative radiotherapy (PRT) could be promising, however, there are few reports of PRT for tumor bleeding in patients with unresectable PC. Therefore, we evaluated the outcomes of PRT for tumor bleeding in patients with unresectable PC.MethodsWe reviewed the medical records of patients with unresectable PC diagnosed at our institution between May 2013 and January 2022, and identified patients with endoscopically confirmed tumor bleeding who had received PRT. PRT was administered at a total dose of 30 Grays (Gy) in 10 fractions, 20 Gy in 5 fractions, or 8 Gy in a single fraction, and the dose selection was left to the discretion of the attending radiation oncologists.ResultsDuring the study period, 2562 patients were diagnosed as having unresectable PC at our hospital, of which 225 (8.8%) developed GIB. Among the 225 patients, 63 (2.5%) were diagnosed as having tumor bleeding and 20 (0.8%) received PRT. Hemostasis was achieved in 14 of the 20 patients (70%) who received PRT, and none of these patients developed grade 3 or more adverse events related to the PRT. The median time to hemostasis was 8.5 days (range 7–14 days). The rebleeding rate was 21.4% (3/14). The median hemoglobin level increased significantly (p < 0.001) from 5.9 to 9.1 g/dL, and the median volume of red blood cell transfusion tended (p = 0.052) to decrease, from 1120 mL (range 280–3360 mL) to 280 mL (range 0–5560 mL) following the PRT. The median overall survival (OS) was 52 days (95% confidence interval [CI] 39–317). Of the 14 patients in whom hemostasis was achieved following PRT, chemotherapy could be started/resumed in seven patients (50%), and the median OS in these patients was 260 days (95% CI 76–not evaluable [NE]). Three patients experienced rebleeding (21.4%), on days 16, 22, and 25, after the start of PRT.ConclusionThis study showed that PRT is an effective and safe treatment modality for tumor bleeding in patients with unresectable PC.

Combination of carbohydrate antigen 19-9 level and tumor size after neoadjuvant chemoradiation therapy may predict early recurrence of resectable pancreatic ductal adenocarcinoma

BackgroundAlthough the overall survival rate of patients with resectable pancreatic cancer has gradually improved, some patients relapse early and have a poor prognosis. This study aimed to identify the preoperative risk factors for early recurrence after neoadjuvant chemoradiotherapy in patients with resectable pancreatic cancer. MethodsThis study analyzed patients who underwent pancreatectomy after receiving neoadjuvant chemoradiotherapy for resectable pancreatic cancer between January 2009 and June 2021 and excluded those with borderline resectable and unresectable pancreatic cancers. Early recurrence was defined as recurrence within 6 months after surgery. ResultsThis study included 203 patients, of whom 22 experienced early recurrence. The median survival time of patients with early recurrence was 18.3 months, which was significantly worse than that of patients with late recurrence (44.0 months, p < 0.001) or no recurrence (not reached, p < 0.001). Logistic regression analysis revealed that a carbohydrate antigen 19-9 level of >100 units/mL and a T status of ≥T2 after neoadjuvant chemoradiotherapy were independent predictive risk factors for early recurrence. The median recurrence-free survival time of patients with two risk factors was 9.7 months and significantly worse than that of those with either risk factors (20.5 months, p = 0.024) and those with no risk factor (26.2 months, p < 0.001). ConclusionsA combination of a high-level carbohydrate antigen 19–9 and a T status of ≥T2 after neoadjuvant chemoradiotherapy are predictors of early recurrence and may be helpful for selecting patients who require a stronger preoperative treatment.

Prognostic factors of long-term survivors with unresectable pancreatic cancer: a retrospective analysis

Prognostic factors of long-term survivors with unresectable pancreatic cancer: a retrospective analysis

Risk factors for unresectable pancreatic cancer following high-intensity focused ultrasound treatment.

Pancreatic cancer is one of the most aggressive malignant tumors with poor prognosis. High-intensity focused ultrasound (HIFU) is an effective and safe treatment option for advanced pancreatic cancer, however, the survival time of patients after the treatment was different. So, the purpose of this study was to evaluate the relationship between the high-risk characteristics and prognosis of unresectable pancreatic cancer after HIFU treatment. This prospective study included 30 patients with unresectable pancreatic cancer who received HIFU at Beijing Friendship Hospital. Data on patients' tumor size, pain scores, peripheral blood lymphocyte subsets, CA19-9 and contrast enhanced ultrasound (CEUS) features were collected to assess the relationship with overall survival (OS) after HIFU. The median OS from the start of HIFU treatment was 159 days, 95% confidence interval (95% CI): 108-210. The levels of pain were determined by visual analogue scale (VAS) score, and the quartile of the score decreased from 6 (2, 7) to 4 (2, 5) immediately after one session of the treatment (p = 0.001). The diagnostic model showed that high post VAS score and decreasing of peripheral CD4+ T cells were significantly correlated with poor prognosis (p < 0.05), and showed good discrimination ability (AUC = 0.848, 95% CI = 0.709-0.987). HIFU can effectively relieve pain in patients with unresectable pancreatic cancer. Post treatment VAS and change of peripheral CD4+ T cells are independent risk factors affecting the prognosis in patients with unresectable pancreatic cancer after HIFU treatment.

Association between BRCA Gene Variants and the Response to Modified FOLFIRINOX in Patients with Unresectable Pancreatic Cancer.

We investigated the effect of modified FOLFIRINOX (mFFX) in unresectable pancreatic cancer by retrospectively analyzing the cases of 43 patients who underwent BRCA testing (germline, n=11; somatic, n=26; both germline and somatic, n=6). The association between BRCA mutations and therapeutic effect was clarified. Six patients tested positive for germline pathogenic variants. Familial pancreatic cancer (33% vs. 3%, p=0.006) and peritoneal disseminated lesions (66% vs. 8%, p<0.001) were significantly more common in patients with germline pathogenic variants. The partial response (PR) rate was 100% in the germline BRCA-positive patients, and 27% in the germline BRCA-negative patients (p<0.001). The median progression-free survival (PFS) was not reached for any germline BRCA-positive patients but was 9.0 months for the germline BRCA-negative patients (p=0.042). Patients with stage IV BRCA-associated pancreatic cancer had better overall survival than those with non-BRCA-associated pancreatic cancer, although the difference was nonsignificant (not reached vs. 655 days, p=0.061). Our results demonstrate that a PR and prolonged PFS can be expected in germline BRCA-positive patients after treatment with mFFX. Our findings also suggest that germline BRCA pathogenic variants may be useful as biomarkers for the therapeutic effect of mFFX in patients with pancreatic cancer.

Analysis of the cost-effectiveness of proton beam therapy for unresectable pancreatic cancer in Japan.

Proton beam therapy (PBT) has recently been included in Japan's social health insurance benefits package. This study aimed to determine the cost-effectiveness of PBT for unresectable, locally advanced pancreatic cancer (LAPC) as a replacement for conventional photon radiotherapy (RT). We estimated the incremental cost-effectiveness ratio (ICER) of PBT as a replacement for three-dimensional conformal RT (3DCRT), a conventional photon RT, using clinical evidence in the literature and expense complemented by expert opinions. We used a decision tree and an economic and Markov model to illustrate the disease courses followed by LAPC patients. Effectiveness was estimated as quality-adjusted life years (QALY) using utility weights for the health state. Social insurance fees were calculated as the costs. The stability of the ICER against the assumptions made was appraised using sensitivity analyses. The effectiveness of PBT and 3DCRT was 1.67610615 and 0.97181271 QALY, respectively. The ICER was estimated to be ¥5,376,915 (US$46,756) per QALY. According to the suggested threshold for anti-cancer therapy from the Japanese authority of ¥7,500,000 (US$65,217) per QALY gain, such a replacement would be considered cost-effective. The one-way and probabilistic sensitivity analyses demonstrated stability of the base-case ICER. PBT, as a replacement for conventional photon radiotherapy, is cost-effective and justifiable as an efficient use of finite healthcare resources. Making it a standard treatment option and available to every patient in Japan is socially acceptable from the perspective of health economics.

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.

Neoadjuvant Stereotactic MR-Guided Ablative Radiation Therapy (SMART) and Surgical Outcomes in Patients with Pancreatic Cancer

The benefit of neoadjuvant radiation therapy for patients undergoing surgery for pancreatic ductal adenocarcinoma (PDAC) remains unclear. Stereotactic MR-guided adaptive radiation therapy (SMART) treatment to ablative doses is a newer technique that is well tolerated and has increased local control in unresectable pancreatic cancer. For resectable pancreatic cancer, neoadjuvant SMART has the potential to decrease local recurrence risk and positive margin rates. However, there is concern for perioperative risks associated with ablative dose treatments. We report the efficacy and safety of surgical resection in patients who have received neoadjuvant SMART at our institution. We conducted a retrospective analysis of all consecutive patients diagnosed with PDAC who had noted vascular involvement of the celiac axis, superior mesenteric, and/or portal vessels between January 2016 and December 2022 at a single, high-volume, academic institution. Perioperative events were defined according to the Clavien-Dindo classification. The Kaplan Meier method was applied to estimate disease free survival (DFS) and overall survival (OS). Seventeen patients with PDAC and vessel involvement at time of diagnosis who received SMART were included. Median follow-up time was 14.3 months; all patients underwent surgery, at a median time after radiation of 28 days (range: 15 - 90). Median length of postoperative stay was 7 days (range: 3 - 15). Five patients (29%) underwent vascular resection. Fifteen patients (88%) achieved R0 resection, with two R1 resections noted at the SMA and pancreatic neck respectively. Seven patients (41%) had adverse events attributable to surgery, with the majority being defined as abscess or infection (n = 5; 29%). One (6%) Clavien-Dindo grade III or higher toxicity was observed - a cortical cerebrovascular event following surgery. No major bleeding events requiring surgical intervention were noted. At time of event censorship, there were no observable locoregional failures. The median DFS and OS were not reached; however, 1-year DFS and OS were 62% and 87%, respectively. Neoadjuvant SMART appears to be safe, with low rates of surgical complications and promising outcomes. Further identification of patients for this approach requires additional investigation.

Evaluation of the Possibility of Dose Realignment Adaptation by Shifting the Isocenter in Proton Beam Therapy for Pancreatic Cancer

In pancreatic cancer, a tumor is surrounded by the gastrointestinal (GI) tract, which is subject to changes in location, shape, and contents. Due to these inter-fractional changes, proton beam therapy (PBT) for pancreatic cancer may result in unintentionally high doses to the GI tract. Daily adaptive re-planning can solve this problem, but is not yet established with PBT due to its resource intensive characteristics. This study aims to evaluate the GI tract dose using weekly computed tomography (CTw) and the possibility of dose realignment adaptation by shifting the isocenter (IC) of the PBT plan, which does not require re-planning. We retrospectively analyzed 6 consecutive patients with unresectable pancreatic cancer treated with real-time-image gated PBT using a fiducial marker. The planning CT was scanned at the natural expiration of respiration and a PBT plan of 60 GyE in 25 fractions (baseline plan, PLANbase) was created. The CTw images were acquired the day before start of PBT and once a week during the PBT course thereafter. The PLANbase was rigidly transferred to the CTw based on the relationship between the three-dimensional coordinates of the fiducial marker and those of the IC in the PLANbase. The PLANeval was created by recalculating the PLANbase on the CTw. We evaluated the doses to the stomach, duodenum, and intestines in the PLANeval according to the following criteria: Dmax of the stomach < 60 GyE, duodenum and intestines < 55 GyE, and D1cc of the stomach < 55 GyE, duodenum and intestines < 54 GyE. In addition, we investigated the GI tract dose realignment adaptation for the PLANeval with its IC shifted 2mm, 4mm, and 6mm in each of 6 directions (right, left, ventral, dorsal, cranial, and caudal), respectively. A total of 35 PLANeval were created for the CTw. In the PLANbase of the 6 patients, the average of Dmax and D1cc of the stomach, duodenum and intestines were 50.7 GyE (range, 46.7-53.6) and 50.0 GyE (45.0-53.2), 49.2 GyE (44.3-51.7) and 48.8 GyE (43.7-51.5), and 49.2 GyE (44.8-52.0) and 48.9 GyE (44.6-51.8), respectively. In the PLANeval, the average of Dmax and D1cc of the stomach, duodenum, and intestines were 53.3GyE (43.8-61.4) and 52.8 GyE (43.2-61.1), 51.0 GyE (36.1-60.0) and 50.3 GyE (35.4-59.8), and 52.5 GyE (36.6-61.0) and 51.9 (34.4-60.9) GyE, respectively. Twenty-two of the 35 PLANeval (63 %) did not meet at least one of the GI tract dose criteria. In 11 of 22 PLANeval with higher doses to the GI tract, the IC shift resulted in GI dose reductions and all dose criteria were met. The minimum amount of the IC shift required to meet the criteria was 2 mm for 8 plans and 4 mm for 3 plans. The remaining 11 PLANeval did not meet the criteria using dose realignment adaptation by shifting the isocenter. Adaptive replanning is necessary for PBT for pancreatic cancers due to excessive GI tract doses in more than 60% of the plans. Dose realignment adaptation by shifting the IC, which does not require re-planning, may be an option in adaptive treatment strategies.

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.

ROS-Sp1 axis is involved in thermochemotherapy-enhanced sensitivity of pancreatic cancer cells to gemcitabine.

Gemcitabine (GEM)-based chemotherapy represents the first choice for locally unresectable advanced pancreatic cancer, while the benefit is limited due to acquired chemoresistance or drug delivery insufficiency. Hyperthermia treatment potentially improves the clinical efficacy of GEM. However, the underlying mechanism is incompletely revealed. Our study aims to investigate the effect and involved mechanism of thermochemotherapy on cell survival. Pancreatic cancer cells PANC-1 and ASPC-1 were either treated with GEM or thermochemotherapy, then cell viability, apoptosis, migration, invasion, reactive oxygen species (ROS) production, and Sp1 expression were evaluated. The results showed that GEM dose and time-dependently affected cell viability, and 30 μM GEM achieved favorable effect in suppressing cancer cell growth. Meanwhile, hyperthermia preconditioning (43°C for 60 min) 24 h before GEM treatment yielded superior effect than other treatment sequence. GEM caused significant cell apoptosis and proapoptotic genes of both cancer cells, and thermochemotherapy further promoted apoptosis and genes transcription, accompanied by excessive ROS production. Thermochemotherapy was superior to GEM in suppressing cell migration and invasion of pancreatic cancer cells. Meanwhile, GEM significantly reduced Sp1 mRNA and protein and its downstream gene Cox-2, and thermochemotherapy further suppressed their expressions. ROS elimination with N-acetyl-l-cysteine notably neutralizes the suppressive effect of GEM and thermochemotherapy on cell growth and expressions of Sp1 and Cox-2. In conclusion, thermochemotherapy inhibited pancreatic cell viability, migration and invasion, and promoted cell apoptosis by inducing excessive ROS production, which subsequently suppressed Sp1 expression and the downstream Cox-2.

Parallel administration of nanoliposomal irinotecan and levo-leucovorin for pancreatic cancer

BackgroundNanoliposomal irinotecan (nal-IRI) plus 5-fluorouracil (5-FU)/levo-leucovorin (Levo-LV) was approved for unresectable pancreatic cancer (UR-PC) in March 2020 in Japan. Levo-LV is administered by intravenous infusion over 120 min following 90 min intravenous infusion of nal-IRI (conventional method), causing a significant burden on both patients and the outpatient chemotherapy room owing to the prolonged administration time. Thus, from July 2021, we introduced the simultaneous intravenous administration of nal-IRI and Levo-LV (parallel method) with the approval of the institutional regimen committee.MethodsWe retrospectively reviewed the data of 69 patients with UR-PC who received nal-IRI plus 5-FU/Levo-LV at our hospital between June 2020 and October 2021. We examined the safety of the parallel method and compared the treatment outcomes and administration times between the two methods.ResultsThe median age was 66 years (54%, male). Disease statuses were locally advanced, metastatic, and postoperative recurrence after pancreatectomy in 7, 50, and 12 patients, respectively. Nal-IRI plus 5-FU/Levo-LV treatment was second and third-line or later in 35 and 34 patients, respectively. No intravenous line problems were observed during the parallel administration of nal-IRI and Levo-LV. Although there were no significant differences in response rates and adverse events between the two methods, the administration time was significantly shorter in the parallel method than in the conventional method.ConclusionThe parallel administration of nal-IRI and Levo-LV is clinically safe and not inferior in efficacy. Moreover, parallel administration may offer convenience to patients and healthcare workers by reducing administration time.

Surgical pancreatic biopsies for cases with locally advanced pancreatic cancer with inconclusive histology after interventional biopsy

BackgroundHistopathological confirmation of malignancy is mandatory in patients with unresectable pancreatic cancer before initiation of palliative chemotherapy. When interventional biopsy proves unsuccessful, laparoscopic or open surgical biopsies become necessary. Methods66 consecutive surgical biopsies of the pancreas performed at a single institution between 01/2010 and 04/2020 were analyzed retrospectively. We analyzed sensitivity of histopathological confirmation of malignancy as well as complication rates of laparoscopic and open surgical biopsies in patients with suspected advanced pancreatic cancer after unsuccessful interventional biopsies. Results8 complications were observed in 46 patients requiring only a pancreatic biopsy (17.4 %) while in 13 of 20 patients complications were observed when additional procedures were necessary (65 %). Major complications CD ≥ III were observed in the “biopsy +/- port” group in 4 of 46 patients and in the “biopsy + additional procedure” cohort in 9 of 20 patients (8.7 vs. 45 %, p < 0.001). Despite the trend to reduced perioperative complications in laparoscopic biopsies, the reduction did not reach statistical significance when compared to open resections (11.1 vs. 26.3 %, p = 0.18). Surgical pancreatic biopsies reached a sensitivity regarding the correct definite histopathological result of 90.32 %, specificity was 100 %. ConclusionBoth laparoscopic and open biopsies can be performed at acceptable complication rates CD ≥ III of 8.7 % and present a valuable option after failure of image-guided techniques for biopsy. Additional operative measures in locally advanced pancreatic carcinoma ought to be critically reflected due to a substantially higher complication rate CD ≥ III of 45 %. Key messageLaparoscopic and open surgical biopsies in patients with unresectable pancreatic cancer demonstrate a high diagnostic sensitivity at acceptable complication rates. This finding is important because it provides further support for surgical biopsies to avoid delay before initiation of palliative therapy.

Normo- or Hypo-Fractionated Photon or Proton Radiotherapy in the Management of Locally Advanced Unresectable Pancreatic Cancer: A Systematic Review.

Clinical studies published from 2012 to 2022 were systematically reviewed using PubMed, MEDLINE (via PubMed) and Cochrane databases. Different radiotherapy-related data were extracted and analyzed. A total of 31 studies matched the inclusion criteria. Acute toxicity was less remarkable in stereotactic body radiotherapy (SBRT) compared to conventionally fractionated radiotherapy (CFRT), while in proton beam therapy (PBT) grade 3 or higher acute toxicity was observed more commonly with doses of 67.5 Gy (RBE) or higher. Late toxicity was not reported in most studies; therefore, comparison between groups was not possible. The range of median overall survival (OS) for the CFRT and SBRT groups was 9.3-22.9 months and 8.5-20 months, respectively. For the PBT group, the range of median OS was 18.4-22.3 months. CFRT and SBRT showed comparable survival outcomes with a more favorable acute toxicity profile for SBRT. PBT is a promising new treatment modality; however, additional clinical studies are needed to support its efficacy and safety.

Intratumoral Air Bubbles and Hematemesis as Predictors of Pseudoaneurysm Rupture in Unresected Pancreatic Cancer.

Objective Pseudoaneurysm rupture associated with unresected pancreatic cancer can cause rare but fatal hemobilia and gastrointestinal bleeding. This study aimed to identify factors predicting pseudoaneurysm rupture. Methods We conducted a single-center case-control study of unresected pancreatic cancer patients treated at Shizuoka General Hospital between January 2011 and July 2020 using a retrospective cancer registry database. Included in the study were 611 consecutive patients with unresected pancreatic cancer, of whom 55 developed overt upper gastrointestinal bleeding or hemobilia. Twenty patients were excluded, as they had not undergone contrast-enhanced computed tomography (CT) or angiography. Patients were classified into pseudoaneurysm and non-pseudoaneurysm groups. One patient with arterial bleeding but without obvious pseudoaneurysm was included in the pseudoaneurysm group. Factors predicting pseudoaneurysm rupture at the onset of overt gastrointestinal bleeding were investigated using a logistic regression analysis. CT findings revealing air bubbles inside the tumor were described as intratumoral air bubbles. Results Thirty-five patients were included (15 in the pseudoaneurysm group, 20 in the non-pseudoaneurysm group). In the multivariate analysis, intratumoral air bubbles [odds ratio (OR), 12.9; 95% confidence interval (CI), 2.14-77.9; p=0.005] and hematemesis (OR, 6.30; 95% CI, 1.03-38.6; p=0.047) were independent predictors of pseudoaneurysm rupture. In addition, patients who experienced successful hemostasis and were re-administered chemotherapy survived more than six months. Conclusions This study reveals that intratumoral air bubbles and hematemesis may predict pseudoaneurysm rupture at the onset of overt gastrointestinal bleeding. For patients presenting these findings, an examination with conventional or CT angiography may lead to an early diagnosis and improve the patient prognosis.

Celiac plexus neurolysis in treatment of chronic pain syndrome in patients with unresectable pancreatic cancer

Celiac plexus neurolysis in treatment of chronic pain syndrome in patients with unresectable pancreatic cancer

Circulating tumor DNA in unresectable pancreatic cancer is a strong predictor of first-line treatment efficacy: The KRASCIPANC prospective study

BackgroundThere is no robust predictor of response to chemotherapy (CT) in unresectable pancreatic adenocarcinomas (UPA). The objective of the KRASCIPANC study was to analyze the kinetics of cell-free DNA (cfDNA)/circulating tumor DNA (ctDNA) as a predictor of response to CT in UPA. MethodsBlood samples were collected just before first CT and at day 28. The primary endpoint was the kinetics of KRAS-mutated ctDNA by digital droplet PCR between D0 and D28 as a predictor of progression-free survival (PFS). ResultsWe analyzed 65 patients with a KRAS-mutated tumor. A high level of cfDNA and KRAS-mutated ctDNA at D0, as well as the presence of KRAS-mutated ctDNA at D28, were strongly associated with lower centralized disease control rate (cDCR), shorter cPFS and OS in multivariate analysis. A score combining cfDNA level at diagnosis ≥ or <30 ng/mL and presence or not of KRAS-mutated ctDNA at D28 was an optimal predictor of cDCR (OR=30.7, IC95% 4.31–218 P=.001), PFS (HR=6.79, IC95% 2.76–16.7, P<.001) and OS (HR=9.98, IC95% 4.14–24.1, P<.001). ConclusionA combined score using cfDNA level at diagnosis and KRAS-mutated ctDNA at D28 is strongly associated with patient survival/response to chemotherapy in UPA. Trial RegistrationClinicalTrials.gov Identifier: NCT04560270

A phase I/II study of durvalumab and stereotactic ablative body radiotherapy (SABR) in locally advanced (LA) and borderline resectable (BR) pancreatic cancer.

4164 Background: Pancreatic cancer (PC) is largely refractory to immune checkpoint blockade (ICB) in genomically unselected patients (pts). Synergistic effects of combined ICB and radiotherapy have been suggested in varied solid tumors. Few studies have evaluated this approach in pts with PC. We sought to evaluate the safety and efficacy of PD-L1 inhibitor durvalumab (D) and SABR after induction chemotherapy, in LA and BR PC. Herein, we present phase II data from two cohorts. Methods: A multi-institutional, non-randomized phase 1/2 trial of SABR and D was conducted at Cedars-Sinai Medical Center (CS) and Memorial Sloan Kettering (MSK). Key eligibility: ECOG 0-1; unresectable PC, with stable/responding disease following 2-3 cycles gemcitabine and nab-paclitaxel (GnP) or 4-6 months (m) FOLFIRINOX (FFX). CS enrolled pts with BR and LA PC; MSK enrolled pts with LA PC only. All pts received SABR between dose 1 and 2 of D, with slight variation in ablative radiation techniques (CS: 33Gy/5#; MSK: MRI adaptive ablative radiation, 50Gy/5#). D dosed on day 1: 750mg x 4 doses Q14 days, and subsequently Q2 or Q4 weeks x 1 year total, or until resection, progression of disease (POD), or limiting toxicity. Primary endpoint: 6-month progression free survival (6 m PFS). Secondary endpoints: rate of downstaging to resectability, objective response by RECIST v1.1, duration of response, PFS, Overall Survival (OS). PFS and OS estimated from consent date using Kaplan-Meier method. Association between surgery and outcomes was analyzed as a time dependent covariate in univariate Cox regression models for OS and PFS. To assess immunogenomic biomarkers of response, pre- and on-treatment tissue, blood and microbiome samples were gathered. Results: Between 08/2017 and 05/2022, N= 36 enrolled. Median age 67.5 years (range 48-79), 39% (14/36) female. Performance Status: N=12 (33%) ECOG 0; N= 24 (67%) ECOG 1. Median duration chemotherapy: 3.5 m (range 1.4, 5.8). Staging: N=31 (86%) LA; N=5 (14%) BR. N = 9 (25%) underwent resection; all R0. Conversion to resection was not associated with PFS (HR 0.45; 95% CI 0.17, 1.17, p=0.1) or OS (HR 0.69; 95% CI 0.26, 1.84, p=0.5). Survival and response data summarized in table. Toxicities of special interest: Grade 3 treatment-related: in N= 7; diarrhea N= 2; elevated AST/ALT N= 2; lipase/amylase elevation, N=1; nausea N=1. Grade 4: amylase elevation N=1. Conclusions: D and SABR after induction chemotherapy in LA and BR PC is safe, had an encouraging 6-m PFS of 69% and favorable R0 resection rate, warranting further evaluation. Immuno-genomic biospecimen analyses underway. Clinical trial information: NCT03245541 . [Table: see text]