Operable Pancreatic Cancer Research Articles

Comparative Efficacy of 21 Treatment Strategies for Resectable Pancreatic Cancer: A Network Meta-Analysis.

The primary treatment for operable pancreatic cancer (PC) involves surgery followed by adjuvant therapy. Nevertheless, perioperative or neoadjuvant chemotherapy (CT) may be used to mitigate the likelihood of recurrence and mortality. This network meta-analysis (NMA) assesses the comparative efficacy of various treatment approaches for resectable PC. A thorough search was carried out on January 31, 2023, encompassing PubMed/MEDLINE, Cochrane Library, and Embase databases. We incorporated randomized clinical trials (RCTs) that compared surgical interventions with or without (neo)adjuvant or perioperative therapies for operable PC. We conducted a fixed-effects Bayesian NMA. We presented the effect sizes in terms of hazard ratios (HRs) for overall survival (OS) along with 95% credible intervals (95% CrIs). The treatment was deemed statistically superior when the 95% credible interval (CrI) did not encompass a null value (hazard ratio < 1). Treatment rankings were established based on the surface under the cumulative ranking curve (SUCRA). A total of 24 studies were incorporated, comparing 21 treatments with surgery in isolation. Eleven treatments showed superior efficacy compared to surgery alone, with HRs ranging from 0.38 for perioperative treatments to 0.73 for adjuvant 5-fluorouracil. After the exclusion of studies conducted in Asia, it was found that the perioperative regimen of gemcitabine combined with nab-paclitaxel was the most effective regimen (SUCRA, p = 0.99). The findings endorse the utilization of perioperative CT, especially multi-agent CT, as the favored intervention for operable PC in Western nations.

National adoption of neoadjuvant chemotherapy: paradigm shift in the treatment of pancreatic cancer

BackgroundThe historical standard of care in treating operable pancreatic cancer via upfront surgery has been challenged recently using a neoadjuvant approach. The aim of the study is to examine the national practice patterns in the management of pancreatic cancer with an emphasis on the trends of neoadjuvant systemic therapy use. MethodsThis is a cross-sectional time-series study using the National Cancer Database from 2006 to 2019. Patients who underwent resection for stage I-II pancreatic adenocarcinoma were selected. ResultsOverall, 25% of patients had neoadjuvant chemotherapy, 49% had surgery followed by adjuvant chemotherapy and 26% had surgery alone. The rate of neoadjuvant chemotherapy has increased from 11% in 2006 to 43% in 2019. There was a decrease in the rate of surgery followed by chemotherapy from 48% to 38%, and a decrease in the rate of surgery alone from 41% to 19%. The rate of radiation therapy use has decreased over time, as has the resection rate, while median overall survival has steadily improved over the years. ConclusionsIn 2019, the rate of using neoadjuvant systemic therapy overtook the rate of surgery first followed by adjuvant systemic therapy, marking a pragmatic national shift in the clinical management of pancreatic cancer.

Role of preoperative malnutrition and symptom severity in anorexia-cachexia-related quality of life in patients with operable pancreatic cancer

PurposeThis study assessed the changes in malnutrition status, symptom severity, and anorexia-cachexia-related quality of life (QoL) before and after pancreatic surgery and identified significant factors associated with changes in anorexia–cachexia-related QoL in patients with operable pancreatic cancer. MethodsIn total, 76 patients with pancreatic cancer who were scheduled to undergo surgery were recruited from a medical center in northern Taiwan. The Mini Nutritional Assessment, Symptom Severity Scale, and Functional Assessment of Anorexia–Cachexia Therapy scale were used to assess the patients’ nutritional status, symptom severity, and anorexia–cachexia-related QoL, respectively. Bioelectrical impedance analysis was performed using X-Scan Plus II to assess body composition. A generalized estimating equation approach was used to identify significant factors associated with anorexia–cachexia-related QoL. ResultsIn total, 42.1% of the patients had malnutrition or were at risk of malnutrition before surgery. Preoperative malnutrition (β = −3.857, p = .001) and higher early satiety (β = −0.629, p = .005), insomnia (β = −0.452, p = .025), and pain (β = −0.779, p < .001) were associated with lower anorexia-cachexia-related QoL. ConclusionClinicians should actively assess the nutritional status of patients with pancreatic cancer before surgery and provide symptom cluster management interventions to improve nutrition, insomnia, and pain, which is crucial for enhancing patients’ anorexia–cachexia-related QoL.

Biliary Adverse Events During Neoadjuvant Therapy for Pancreatic Cancer.

To describe a high-volume experience with biliary drainage before neoadjuvant therapy (NAT) for patients with operable pancreatic cancer (PC) and characterize the association between biliary adverse events (BAEs) and patient outcome. Patients with PC presenting with biliary obstruction require durable decompression before NAT. Patients with operable PC and tumor-associated biliary obstruction were examined and grouped by the presence or absence of a BAE during NAT. The incidence, timing, and management of BAEs are described, and outcomes, including the completion of all treatment and overall survival (OS), were compared. Of 426 patients who received pretreatment biliary decompression, 92 (22%) experienced at least 1 BAE during NAT, and 56 (13%) required repeat intervention on their biliary stent. The median duration of NAT was 161 days for all patients and was not different in the group that experienced BAEs. The median time from initial stent placement to BAE was 64 days. An interruption in the delivery of NAT (median 7 days) occurred in 25 (6%) of 426 patients. Among 426 patients, 290 (68%) completed all NAT, including surgery: 60 (65%) of 92 patients with BAE and 230 (69%) of 334 patients without BAE ( P =0.51). Among 290 patients who completed NAT and surgery, the median OS was 39 months, 26 months for the 60 patients with BAE, and 43 months for the 230 patients without BAE ( P =0.02). During extended multimodal NAT for PC, 22% of patients experienced a BAE. Although BAEs were not associated with a significant interruption of treatment, patients who experienced a BAE had worse OS.

The Effect of Preoperative Oil Chemoembolization Techniques on the Results &#x0D; of Combined Treatment of Operable Pancreatic Cancer

Background: Pancreatogastroduodenal resection is widely used for the treatment of pancreatic cancer but the 5-year survival rate does not exceed 10%. The treatment should be combined, but the question of the expediency of neoadjuvant therapy (NAT) with initially operable cancer has not been resolved.&#x0D; Aims: Substantiation of the expediency of the use of preoperative intra-arterial interventions in the combined treatment of patients with operable pancreatic cancer and the study of the impact of the technical features of the intervention on the treatment results.&#x0D; Materials and methods: The study included 92 patients (45 men and 47 women; mean age 63.910.1 years, T2N0M0 n=13; T3N0M0 n=32; T2N1M0 n=1; T4N0and1M0 n=46) who received combined treatment for the period 2014-2017.In I group, n=45 patients, the NAT was not performed.In II group, n=47 patients underwent intra-arterial oil chemoembolization of the pancreas with an emulsion of oil contrast and gemcitabine concentrate 400 mg/m2.The technique of distributive embolization of the artery gastroepiploica (GEA) differed: in IIA group, n= 22 patients with a spiral; in IIB group, n=25 patients with a temporarily inflated balloon.All 92 patients underwent radical surgery and received adjuvant chemotherapy based on gemcitabine 1000 mg/m2 in 1,8.15 days, 6 cycles. The frequency of specific and general postoperative complications was analyzed. For control, ultrasound, CT with contrast, CA 19-9 antigen level, general and biochemical blood tests were used. For 5 years, the results of each patient were tracked. The primary endpoints were overall (OS) and relapse-free (RFS) survival.&#x0D; Results: Postembolization syndrome did not affect the timing of the operation. The edematous form of acute pancreatitis was noted in 11 (50%) patients of group IIA and in 5 (20%) patients of group IIB, (p=0.043). Destructive pancreatitis was not marked. The overall 1-year survival rate (OS) in I group (n=31) was 68.9%, in II group (n=40) 85.1%, (p=0.062). The 2-years OS was: in I group (n=19) 42.2%, in II group (n=30) 63.8%, (p=0.042). The 3-year OS was: in I group (n=9) 20%, in II group (n=19) 40.4%, (p=0.021). The 4-years OS was: in I group (n=4) 8.9%, in II group (n=7) 14.8%, (p=0.387). The 5-year OS was: in I group 0, in II group (n=2) 4.3%, (p=0.168). The 1-year RFS was: in I group (n=23) 57.1%, in II group (n=29) 61.7%, (p=0.316). The 2-years RFS was: in I group (n=10) 22.2%, in II group (n=23) 48.9%, (p=0.012). The 3-years RFS was: in I group (n=7) 15.6%, in II group (n=16) 34%, (p=0.047). The 4-years RFS was: in I group (n=3) 6.7%, in II group (n=5) 10.6%, (p=0.568). The 5-years RFS was: in I group 0, in II group (n=1) 4%, (p=0.333).&#x0D; Conclusions: The results of the study confirm the feasibility of using preoperative intra-arterial interventions in the combined treatment of pancreatic cancer. There was a significant difference in the rates of 2-year and 3-year OS and RFS in patients receiving such therapy. The technique of occlusion of the artery gastroepiploica with a balloon probably provides more preferable results.

CA19-9 Response to First-Line Neoadjuvant FOLFIRINOX and Second-Line Gemcitabine/Nab-Paclitaxel for Patients with Operable Pancreatic Cancer.

Response to second-line (2L) neoadjuvant therapy for operable pancreatic cancer (PC) is understudied. This study examined carbohydrate antigen 19-9 (CA19-9) response to first-line (1L) and 2L chemotherapy. The study identified patients with operable PC and elevated CA19-9 (≥35U/mL with total bilirubin <2 mg/dL) who received 1L FOLFIRINOX (FFX). The patients were restaged after 2 months and based on response, received additional FFX or gemcitabine/nab-paclitaxel (GnP) as part of total neoadjuvant therapy. Response was defined as a decrease in tumor size on computed tomography (CT) imaging or a decline in CA19-9 of 50% or more and preserved performance status. For operable PC with an elevated CA19-9, 108 patients received 1L FFX. After 2 months of chemotherapy, the decision was made to continue FFX (FFX ≥ FFX) for 76 (70%) of the 108 patients and switch to GnP (FFX ≥ GnP)) for 32 (30%) of the patients. Of the 32 FFX ≥ GnP patients, 27 had no evidence of radiographic or biochemical (CA19-9) response to 1L FFX. Of these 27 patients, 26 (96%) demonstrated a response to 2L GnP. After 4 months of chemotherapy, 62 (82%) of the 76 FFX ≥ FFX patients had a CA19-9 response compared with 31 (97%) of the 32 FFX ≥ GnP patients (p = 0.04). Lack of biochemical response to 2 months of 1L FFX may identify a subgroup of patients with a very high rate of response to 2L GnP, emphasizing the importance of assessing treatment response at 2-month intervals.

Lipid Metabolic Reprogramming Extends beyond Histologic Tumor Demarcations in Operable Human Pancreatic Cancer.

In clinically operable pancreatic cancer, regions distant from malignant cells already display proteomic changes related to lipid transport and metabolism that affect prognosis and may be pharmacologically targeted.

Neoadjuvant therapy in pancreatic cancer: a review and update on recent trials.

Neoadjuvant therapy (NAT) has been enthusiastically embraced for patients with operable pancreatic cancer (PDAC) in hopes of improving survival. However, the rapid integration of clinical trial data has made it difficult to discern optimal treatment strategies. The goal of this review is to summarize notable recent trials and their contributions to the field. The results of ESPAC-5F, NEOLAP-AIO-PAK-0113, SWOG1505, PREOPANC, HyperAcutePancreas, and ALLIANCE A021501 are reviewed in detail. These studies sequentially evaluate the different neoadjuvant treatment strategies, use of neoadjuvant chemoradiation, and immunotherapy in resectable, borderline-resectable, and locally advanced PDAC. Resection rate ranged from 24.4 to 95.7% (median 64.9%). These trials demonstrate median survival ranging from 14.9 to 41.0 months with progression-free survival ranging from 7.7 to 24.2 months. Survival results may be confounded by ability to reach resection, use of modern chemotherapy vs. gemcitabine monotherapy, and inclusion of locally advanced PDAC. Several upcoming trials will directly examine efficacy of NAT vs. adjuvant therapy, chemoradiation in the NAT setting, and molecular testing-driven chemotherapy selection. NAT is associated with improved survival for patients with borderline resectable PDAC but broader efficacy for resectable PDAC and optimal treatment strategy have yet to be defined.

Stent Selection in Preoperative Biliary Drainage for Patients With Operable Pancreatic Cancer Receiving Neoadjuvant Therapy: A Meta-Analysis and Systematic Review.

With the increasing use of neoadjuvant therapy (NAT) in patients with pancreatic cancer to reduce tumor burden on prognosis, preoperative biliary drainage (PBD) is becoming increasingly necessary. The aim of this study was to summarize the latest evidence and compare the clinical efficacy of metal stents (MS) and plastic stents (PS) in patients undergoing neoadjuvant therapy for operable pancreatic cancer. Eligible studies were searched in PubMed, Embase and Cochrane Library from their inception to September 2021. In this study, RevMan 5.4 was used to perform the analyses. Two randomized controlled trials (RCTs) and six retrospective studies with 316 patients were included. All patients had pancreatic cancer and received NAT before surgical resection. Meta-analysis showed that the rate of endoscopic reintervention in MS (26/143, 18%) group was lower than that of PS (122/153, 80%) group (P < 0.05). The rate of stent-related complications in MS group was lower (18/118, 15%) than that of PS (52/117, 44%) group (P = 0.02). But there were no significant differences in operative time, operative blood loss, overall postoperative complications, postoperative hospitalization days and total medical costs between the two groups. For operable pancreatic cancer patients undergoing NAT surgery, MS was preferred over PS in terms of the incidence of endoscopic reintervention and stent-related complications. More clinical trials are needed in the future to confirm these data with higher levels of evidence.

Synchronous Operable Pancreatic and Breast Cancer Without Genetic Mutation: A Literature Review and Discussion.

BackgroundSynchronous cancers are rarely detected when working-up a patient for a primary cancer. Neoadjuvant management of synchronous breast and pancreatic cancers, without a germline mutation, has yet to be discussed. Two patients were diagnosed with synchronous breast and pancreatic cancers at our institution over the last decade. A literature review was performed to evaluate the current evidence stance.ResultsThe first patient was 61-years old and diagnosed with a HER2+ breast cancer. The second patient was 77-years old and diagnosed with a Luminal B breast cancer. The inability to provide concurrent breast and pancreatic neoadjuvant therapy for the HER2+ patient, resulted in upfront surgery. The second patient was able to have both cancers treated simultaneously - neoadjuvant chemotherapy to the pancreas, and neoadjuvant endocrine therapy to the breast.DiscussThere is no single neoadjuvant regimen that treats both pancreatic and breast cancer. The differences in breast cancer sub-types impacted our neoadjuvant options. Our recent experience led us to the hypothesis that breast cancer care dictates treatment, while pancreatic cancer determines survival. There is a significant paucity in the literature regarding synchronous breast and pancreatic cancer.

Adaptive Dynamic Therapy and Survivorship for Operable Pancreatic Cancer

Neoadjuvant therapy is increasingly used in localized pancreatic carcinoma, and survival is correlated with carbohydrate antigen 19-9 (CA19-9) levels and histopathologic response following neoadjuvant therapy. With several regimens now available, the choice of chemotherapy could be best dictated by response to neoadjuvant therapy (as measured by CA19-9 levels and/or pathologic response), a strategy defined herein as adaptive dynamic therapy. To evaluate the association of adaptive dynamic therapy with oncologic outcomes in patients with surgically resected pancreatic cancer. This retrospective cohort study included patients with localized pancreatic cancer who were treated with either gemcitabine/nab-paclitaxel or fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) preoperatively between 2010 and 2019 at a high-volume tertiary care academic center. Participants were identified from a prospectively maintained database and had a median follow-up of 49 months. Data were analyzed from October 17 to November 24, 2020. The adaptive dynamic therapy group included 219 patients who remained on or switched to an alternative regimen as dictated by CA19-9 response and for whom the adjuvant regimen was selected based on CA19-9 and/or pathologic response. The nonadaptive dynamic therapy group included 103 patients who had their chemotherapeutic regimen selected independent of CA19-9 and/or tumoral response. Prognostic implications of dynamic perioperative therapy assessed through Kaplan-Meier analysis, Cox regression, and inverse probability weighted estimators. A total of 322 consecutive patients (mean [SD] age, 65.1 [9] years; 162 [50%] women) were identified. The adaptive dynamic therapy group, compared with the nonadaptive dynamic therapy group, had a more pronounced median (IQR) decrease in CA19-9 levels (-80% [-92% to -56%] vs -45% [-81% to -13%]; P < .001), higher incidence of complete or near-complete tumoral response (25 [12%] vs 2 [2%]; P = .007), and lower median (IQR) number of lymph node metastasis (1 [0 to 4] vs 2 [0 to 4]; P = .046). Overall survival was significantly improved in the dynamic group compared with the nondynamic group (38.7 months [95% CI, 34.0 to 46.7 months] vs 26.5 months [95% CI, 23.5 to 32.9 months]; P = .03), and on adjusted analysis, dynamic therapy was independently associated with improved survival (hazard ratio, 0.73; 95% CI, 0.53 to 0.99; P = .04). On inverse probability weighted analysis of 320 matched patients, the average treatment effect of dynamic therapy was to increase overall survival by 11.1 months (95% CI, 1.5 to 20.7 months; P = .02). In this cohort study that sought to evaluate the role of adaptive dynamic therapy in localized pancreatic cancer, selecting a chemotherapeutic regimen based on response to preoperative therapy was associated with improved survival. These findings support an individualized and in vivo assessment of response to perioperative therapy in pancreatic cancer.

Results of complex treatment of patients with operable pancreatic head cancer using preoperative intra-arterial chemotherapy in combination with radiation therapy in multifractionation mode

The aim of this study was to assess the safety and efficacy of treating patients with operable pancreatic cancer after preoperative intra-arterial infusion of chemotherapy combined with conformal radiation therapy in a multi-fractionation mode. Patients (n = 40) were randomized into two groups: the main one – intra-arterial infusion of chemotherapy + radiation therapy + surgery (n = 20), and control – intra-arterial infusion of chemotherapy + surgery (n = 20). Neoadjuvant therapy consisted of intra-arterial infusion of chemotherapy (chemoembolization of a pancreatic head tumor with oxaliplatin 85 mg/m2) followed by intra-arterial chemo infusion with gemcitabine 1000 mg/m2. In the main group, radiation therapy was also carried out in two fractions per day, 2 Gy with an interval of 4–6 hours, 5 days a week, up to a total dose of 50 Gy. In the main group, the lower incidence of postoperative pancreatitis and the pancreatic fistulas were statistically confirmed, the incidence of grade 2 therapeutic pathomorphisis increased, as well as the median life expectancy.

Goal-directed Neoadjuvant Treatment of Operable Pancreatic Cancer: Achieving CA19-9 Normalization to Chemotherapy Prior to Surgery

Introduction: The optimal length of neoadjuvant chemotherapy (NACT) for patients with operable pancreatic cancer (PC) is controversial. We compared the effect of duration of NACT on carbohydrate antigen 19-9 (CA19-9) response and median overall survival (mOS).

Distinct Survival Outcomes in Subgroups of Stage III Pancreatic Cancer Patients: Taiwan Cancer Registry and Surveillance, Epidemiology and End Results registry

PurposePancreatic cancer is one of the most malignant cancers with poor survival. The latest edition of the American Joint Committee on Cancer (AJCC) staging system classifies the majority of operable pancreatic cancer patients as stage-III, while dramatic heterogeneity is observed among these patients. Therefore, subgrouping is required to accurately predict their prognosis and define a treatment plan. This study conducts a cohort study to provide a more precise classification system for stage-III pancreatic cancer patients by utilizing clinical variables.MethodsWe analyzed survival using log-rank tests, univariate Cox-regression models, and Kaplan-Meier survival curves for stage-III pancreatic ductal adenocarcinoma (PDAC) patients from the Taiwan Cancer Registry (TCR). Patients were further divided into subgroups using classification and regression tree (CART) algorithm. All results were validated using the SEER database.ResultsAmong stage-III PDAC patients, lymph node and tumor grade showed significant association with survival. Patients with N2 stage had higher mortality risks (hazard ratio [HR] = 2.30, 95% confidence interval [CI] 1.71–3.08, p < 0.0001) than N0 patients. Patients with grade 3 also had higher risk of mortality (HR = 3.80, 95% CI 2.25–6.39, p < 0.0001) than grade 1 patients. The CART algorithm stratified stage-III patients into four subgroups with significantly different survival rates. The median survival of the four subgroups was 23.5, 18.4, 14.5, and 9.0 months, respectively (p < 0.0001). Similar results were observed with SEER data.ConclusionsLymph node involvement and tumor grade are predictive factors for survival in stage-III PDAC patients. This new precise classification system can be used to guide treatment planning in advanced-stage pancreatic cancer.

The Role of Radiotherapy in Neoadjuvant Treatment of Patients with Operable Pancreatic Head Cancer

The Role of Radiotherapy in Neoadjuvant Treatment of Patients with Operable Pancreatic Head Cancer

AGITG MASTERPLAN: a randomised phase II study of modified FOLFIRINOX alone or in combination with stereotactic body radiotherapy for patients with high-risk and locally advanced pancreatic cancer

BackgroundAmong patients with non-metastatic pancreatic cancer, 80% have high-risk, borderline resectable or locally advanced cancer, with a 5-year overall survival of 12%. MASTERPLAN evaluates the safety and activity of stereotactic body radiotherapy (SBRT) in addition to chemotherapy in these patients.Methods and designMASTERPLAN is a multi-centre randomised phase II trial of 120 patients with histologically confirmed potentially operable pancreatic cancer (POPC) or inoperable pancreatic cancer (IPC). POPC includes patients with borderline resectable or high-risk tumours; IPC is defined as locally advanced or medically inoperable pancreatic cancer. Randomisation is 2:1 to chemotherapy + SBRT (investigational arm) or chemotherapy alone (control arm) by minimisation and stratified by patient cohort (POPC v IPC), planned induction chemotherapy and institution. Chemotherapy can have been commenced ≤28 days prior to randomisation. Both arms receive 6 × 2 weekly cycles of modified FOLFIRINOX (oxaliplatin (85 mg/m2 IV), irinotecan (150 mg/m2), 5-fluorouracil (2400 mg/m2 CIV), leucovorin (50 mg IV bolus)) plus SBRT in the investigational arm. Gemcitabine+nab-paclitaxel is permitted for patients unsuitable for mFOLFIRINOX. SBRT is 40Gy in five fractions with planning quality assurance to occur in real time. Following initial chemotherapy ± SBRT, resectability will be evaluated. For resected patients, adjuvant chemotherapy is six cycles of mFOLFIRINOX. Where gemcitabine+nab-paclitaxel was used initially, the adjuvant treatment is 12 weeks of gemcitabine and capecitabine or mFOLFIRINOX. Unresectable or medically inoperable patients with stable/responding disease will continue with a further six cycles of mFOLFIRINOX or three cycles of gemcitabine+nab-paclitaxel, whatever was used initially. The primary endpoint is 12-month locoregional control. Secondary endpoints are safety, surgical morbidity and mortality, radiological response rates, progression-free survival, pathological response rates, surgical resection rates, R0 resection rate, quality of life, deterioration-free survival and overall survival. Tertiary/correlative objectives are radiological measures of nutrition and sarcopenia, and serial tissue, blood and microbiome samples to be assessed for associations between clinical endpoints and potential predictive/prognostic biomarkers. Interim analysis will review rates of locoregional recurrence, distant failure and death after 40 patients complete 12 months follow-up. Fifteen Australian and New Zealand sites will recruit over a 4-year period, with minimum follow-up period of 12 months.DiscussionMASTERPLAN evaluates SBRT in both resectable and unresectable patients with pancreatic ductal adenocarcinoma.Trial registrationAustralia New Zealand Clinical Trials Registry ACTRN12619000409178, 13/03/2019.Protocol version: 2.0, 19 May 2019

Impact of G-CSF during neoadjuvant therapy on outcomes of operable pancreatic cancer.

4126 Background: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease characterized by chronic inflammation and a tolerogenic immune response. Neutropenia is a common side effect of cytotoxic chemotherapy, managed with administration of recombinant granulocyte-colony stimulating factor (G-CSF, Filgrastim). The interleukin 17 – G-CSF – neutrophil extracellular trap (NET) axis promotes oncogenesis and progression of PDAC, inhibiting adaptive immunity. We evaluated the impact of G-CSF administration during neoadjuvant therapy (NAT) on oncologic outcomes in patients with operable pancreatic cancer. Methods: A retrospective review of all patients with localized PDAC treated with NAT prior to pancreatic resection between 2014 – 2020 was completed at a single institution. G-CSF administration, type, and dose were collected from inpatient and outpatient medical records. Results: Of 351 patients treated, 138 (39%) received G-CSF during NAT with a median follow-up of 45.8 months. Patients who received G-CSF were younger (64.0 vs 66.7, p = 0.008), had lower BMI (26.5 vs 27.9, p = 0.021), and were more likely to receive 5-FU based chemotherapy (42% vs 28.2%, p &lt; 0.0001), NAT dose reduction (40.6% vs 25.4%, p = 0.003), or experience febrile neutropenia (8.7% vs 3.3%, p = 0.029). No differences were observed in baseline or pathologic tumor staging. In patients who received G-CSF, 130 (94%) received Pegfilgrastim with a median cumulative dose of 12 mg (IQR 6-12). Patients who received G-CSF were more likely to have an elevated post-NAT neutrophil to lymphocyte ratio (45% vs 29.6%, p = 0.004) and systemic immune-inflammation index (39.5% vs 29.6%, p = 0.061). Receiving G-CSF was an independent predictor of perineural invasion (HR 2.4, 95 CI [1.08, 5.5], p = 0.031) and margin positive resection (HR 1.69, 95 CI [1.01, 2.83], p = 0.043). Patients who received G-CSF had decreased overall survival compared to patients who did not receive G-CSF (median OS: 29.2 vs 38.7 months, p = 0.0001). Receiving G-CSF during NAT was an independent negative predictor of progression free (HR 1.38, 95 CI [1.04, 1.83], p = 0.022) and overall survival (HR 2.02, 95 CI [1.45, 2.79], p &lt; 0.0001). In a subset of patients with available pre- and post-NAT serum specimens (n = 28), G-CSF administration resulted in an increased number of citrullinated histone H3 complexes following NAT (+1378±1502 vs -300.7±1147 pg/ml, p = 0.007), indicative of enhanced peripheral NET formation. Conclusions: In patients with localized PDAC receiving NAT prior to surgical extirpation, G-CSF administration is associated with worse oncologic outcomes and should be administered with caution. Prospective randomized as well as confirmatory clinical studies are in order.

High circulating tumour DNA is a strong negative prognostic factor in operable pancreatic cancer

High circulating tumour DNA is a strong negative prognostic factor in operable pancreatic cancer

Presence of perineural invasion determines the need for adjuvant chemotherapy in resected pancreatic carcinoma with node negative disease following neoadjuvant therapy; a multi-institutional analysis

Presenter: Abdulrahman Hammad MBBCh | University of Pittsburgh Medical Center Background: There is growing interest in the potential benefit of neoadjuvant therapy (NAT) for patients with operable pancreatic cancer. NAT is infrequently associated with a complete histologic response in the primary tumor but does result in a robust response in local-regional lymph nodes. Such downstaging of node positive disease to node negative after NAT may have implications for the use of additional postoperative adjuvant therapy (AT). We sought to examine the prognostic implications of AT in node negative patients following NAT and surgery and identify predictors of overall survival (OS). Methods: Patients treated at two high-volume centers who underwent surgical resection following NAT between 2010-2018 and had lymph node negative disease were identified. Kaplan-Meier survival estimates and Cox-proportion hazard regression were performed to identify predictors of OS. Results: Four hundred thirty-one patients were included (mean age 65yrs, 51% females). The predominant NAT was gemcitabine-based (45%) and the median duration of therapy was two months (Interquartile range (IQR): 2, 3). Neoadjuvant chemoradiation (NART) was administered to 65% of the cohort. Pancreatoduodenectomy was performed in 72% and 37% required concomitant vascular resection. The median lymph node yield was 26 (IQR: 19, 34) and 254 (59%), 92 (21%) & 87 (20%) of the cohort had perineural invasion (PNI), lymphovascular invasion (LVI) and residual positive margins (R1) respectively. The median follow-up time was 45.9 months (IQR: 40.7, 54.8). On adjusted analysis, poorly differentiated tumors [HR:1.86 (95%CI: 1.14-3.05), p = 0.013], LVI [HR: 1.45 (95%CI: 1.04-2.01), p = 0.027], and vascular resection [HR: 1.38 (95%CI: 1.06-1.80), p = 0.018] were all independent predictors of survival. PNI was associated with worse survival [HR: 1.72 (95%CI: 1.18, 2.51), p = 0.005] while NART trended towards an association with better survival although did not reach statistical significance [HR: 0.66 (95%CI: 0.42, 1.03, p = 0.065]. Although AT is associated with prolonged survival in the overall cohort [HR: 0.47 (95%CI: 0.26, 0.85), p = 0.013] NART weakens the association [ATxNART interaction; HR: 2.50 (1.40, 4.49), p = 0.002] while PNI strengthens the association [ATxPNI interaction; HR: 0.56 (0.32, 0.97), p = 0.038]. Conclusion: In patients with node negative disease following NAT, PNI (as assessed in the final resection specimen), was associated with worse survival, especially when NART was not administered. Although – in this select cohort – survival is associated with tumor grade, LVI, PNI, NART, and vascular resection, the current analysis suggests that the presence of PNI may identify a high-risk subset within the group of N0 patients for whom AT may be of benefit.

Goal-directed neoadjuvant treatment of operable pancreatic cancer: achieving CA19-9 response to chemotherapy prior to surgery

Goal-directed neoadjuvant treatment of operable pancreatic cancer: achieving CA19-9 response to chemotherapy prior to surgery