ASO Author Reflections: Size Matters in Distal Pancreatic Cancer: Predictor for Failure of Upfront Resection for Radiologically Resectable Disease

445 Background: Malignant ascites confers a poor prognosis in patients with metastatic pancreatic cancer (PC). It is unknown if radiographic ascites in patients with localized disease is a poor prognostic factor and if this finding should be sufficient to avoid upfront local therapies. We aimed to evaluate the survival outcomes of patients with PC and ascites. Methods: Retrospective case control study with overall survival as primary outcome. Eighty newly diagnosed PC patients with ascites (case group) and 80 similar controls without ascites were collected.Cases and controls were matched on age, gender, stage, ECOG performance, surgical treatment, lymph node status and margin status. Overall survival was compared between groups with Cox proportional hazards models by stages, and with a gamma frailty term to account for the correlation between matched pairs on entire cohort. Results: The 80 matched cases included 19 with resectable disease, 9 borderline resectable, 22 locally advanced and 31 with metastatic disease. 29 patients underwent pancreaticoduodenectomy. Table 1 summarizes the overall survival. Ascites patients had higher risk of death compared to patients without ascites (conditional hazard ratio = 1.58 (95% CI: 1.11-2.27), p=0.01). Conclusions: PC patients with ascites have poor overall survival compared to patients without ascites. Even in the setting of resectable disease, survival is similar to patients with advanced disease. This data suggest that all patients with ascites regardless of disease stage should be considered for systemic chemotherapy prior to attempting local treatments. [Table: see text]

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Preliminary safety data from a randomized multicenter phase Ib/II study of neoadjuvant chemoradiation therapy (CRT) alone or in combination with pembrolizumab in patients with resectable or borderline resectable pancreatic cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.4125 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 4125-4125 ◽

Cited By ~ 4

Author(s):

Matthew H. G. Katz ◽

Gauri R. Varadhachary ◽

Todd W. Bauer ◽

Nicolas Acquavella ◽

Nipun B. Merchant ◽

...

Keyword(s):

Pancreatic Cancer ◽

Neoadjuvant Treatment ◽

Safety Data ◽

Neoadjuvant Chemoradiation ◽

Resectable Pancreatic Cancer ◽

Borderline Resectable ◽

Resectable Disease ◽

Post Surgery ◽

Grade 3 ◽

To Receive

4125 Background: Pancreatic cancer (PC) is a challenging target for immunotherapy.Tumor-infiltrating lymphocytes (TILs) do not reach the PC cells in significant numbers due to the presence of stroma and a suppressive microenvironment. Neoadjuvant chemoradiation (CRT) can increase the presence of TILs in the PC microenvironment. We hypothesized that combination of CRT and pembrolizumab can lead to further increase in TILs and their activation. Methods: Patients with resectable or borderline resectable PC have been randomized 2:1 to the investigational treatment (Arm A) to receive pembrolizumab 200mg IV every 3 weeks on days 1, 22, and 43 during concurrent CRT with capecitabine (825 mg/m2 orally twice daily, Monday-Friday, on days of radiation only) and radiation (50.4 Gy in 28 fractions over 28 days) or Arm B to receive only concurrent CRT with capecitabine. Restaging CT scan or MRI is performed at 4-6 weeks after completion of neoadjuvant treatment, and patients with resectable disease will undergo surgical resection. Here we report the preliminary safety data based on 22 enrolled patients. Results: As of February 3-2017,22 patients have been enrolled (14 Arm A and 8 Arm B). 50% of the patients had resectable disease (7 arm A; 4 arm B) and the other 50% had borderline resectable disease (7 Arm A; 4 arm B). Post-neoadjuvant therapy, 6 patients had unresectable disease (3 on each arm), and 14 patients underwent surgery (10 arm A and 4 arm B). There were 7 grade 3 treatment-related toxicities in Arm A (5 patients): 2 grade 3 diarrhea attributed to CRT; 4 grade 3 lymphopenias attributed to pembrolizumab, CRT or the combination; and one patient had elevated alkaline phosphatase probably related to the combination that met the definition of DLT and resolved after holding the treatment and receiving steroids. There was only one grade 3 toxicity on Arm B: lymphopenia attributed to CRT. No grade 4 toxicities have been reported on either arm. There were no major surgical complications reported within 30 days post-surgery. Conclusions: The combination of CRT and pembrolizuamb is safe based on the presented data. Clinical trial information: NCT02305186.

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P-P46 The use of FDG-PET/CT in the pre-operative staging of pancreatic ductal adenocarcinoma

British Journal of Surgery ◽

10.1093/bjs/znab430.268 ◽

2021 ◽

Vol 108 (Supplement_9) ◽

Author(s):

Rebecca Jordan ◽

Duncan Muir ◽

Stijn van Laarhoven ◽

Stephen Falk ◽

Andrew Strickland ◽

...

Keyword(s):

Pancreatic Cancer ◽

Pancreatic Ductal Adenocarcinoma ◽

Fdg Pet ◽

Clinical Information ◽

Ductal Adenocarcinoma ◽

Conventional Imaging ◽

Resectable Disease ◽

Additional Information ◽

Pet Ct ◽

Fdg Pet Ct

Abstract Background  The NICE Quality Standard for Pancreatic Cancer (December 2018) recommends that ‘adults with localised pancreatic cancer on CT(should) have staging using fluorodeoxyglucose positron emission tomography/CT(FDG-PET/CT) before they have surgery, radiotherapy or systemic therapy’. Such FDG-PET/CT staging aims to provide additional information to conventional cross-sectional imaging, thus presenting the most accurate staging of disease. However, the sensitivity and specificity of FDG-PET/CT to deliver relevant additional clinical information must be balanced with potential delays to treatment, and additional cost associated with its use, in the management of a time-critical pathology. Methods Consecutive pancreatic ductal adenocarcinoma(PDAC) patients deemed resectable on conventional imaging, and therefore referred for FDG-PET/CT assessment, were included for analysis. Data were derived from a single tertiary Hepatopancreaticobiliary(HPB) centre between May 2018 and June 2021. Data were collected and analysed from a combination of prospectively-collated electronic databases and paper patient records. Results Of 89 patients analysed, 55(61.7%) patients were male. Primary pancreatic lesions were PET avid in 81 cases(91%). Median time from request to FDG-PET/CT performance was 11 days(Range 1-35). Additional clinical information from FDG-PET/CT was provided in 61(68.5%) patients. Further investigations to assess FDG-PET/CT findings were arranged in 23 patients(25.8%; including liver MRI and EUS), demonstrating that FDG-PET/CT findings were true-positive in 6(26.1%), false-positive in 15(65.2%) and equivocal in 2(8.7%). There was a median delay of 60.5 days(Range 26 to 256) from FDG-PET/CT to surgery in those undergoing additional investigation. In total, a new diagnosis of metastatic/non-resectable disease was made in 14(15.7%) patients, preventing progression to planned operative intervention. Conclusions FDG-PET/CT provided additional information to conventional imaging that led to cancellation of planned operative resection in 14(15.7%) PDAC patients-8 directly and 6 following further investigation. However, there was a median delay of 11 days to FDG-PET/CT and 60.5 days from FDG-PET/CT to surgery in those undergoing additional investigation. Whilst FDG-PET/CT can lead to avoidance of unnecessary surgical intervention in PDAC patients with unsuspected metastatic/non-resectable disease, it can lead to delay, over-investigation, excess cost and anxiety in resectable patients. HPB units should audit their own findings to assess whether the use of FDG-PET/CT should be considered on a standard or selected basis.

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P-P58 The role of PET-CT in the management of pancreatic cancer. A Northern Ireland experience

British Journal of Surgery ◽

10.1093/bjs/znab430.280 ◽

2021 ◽

Vol 108 (Supplement_9) ◽

Author(s):

Lauren Laverty ◽

Stephen McCain ◽

Lloyd McKie

Keyword(s):

Pancreatic Cancer ◽

Northern Ireland ◽

Ct Scan ◽

Surgical Resection ◽

Metastatic Disease ◽

Time Interval ◽

Resectable Disease ◽

Number Of Patients ◽

Pet Ct ◽

The Impact

Abstract Background Diagnosis and staging has proven to be difficult in 10-20% of patients with pancreatic cancer. The PET-PANC study found that PET-CT significantly influenced the staging and management of pancreatic cancer and therefore the NICE guidelines now advise PET-CT in all patients who have localised potentially resectable disease. This study aimed to investigate the impact of PET-CT on the management of pancreatic cancer patients in a single tertiary referral centre. Methods There were 288 patients with pancreatic cancer discussed at the Northern Ireland Regional Hepatobiliary MDM from January 2020 to March 2021. Of these patients, 176 were deemed to have inoperable disease based on initial CT, 5 had borderline resectable disease, 1 had holding chemotherapy due to COVID restrictions and 57 were excluded from surgical resection for a variety of reasons. These included the patient being unfit for surgery, the patient declining operative intervention and an alternative treatment offered as result of COVID-19 pandemic. Therefore, there were 49 patients with pancreatic adenocarcinoma which the MDT concluded should be considered for surgical resection. Results A total of 27 patients who were due to undergo a curative resection had a pre-operative PET-CT scan (55.1%). This demonstrated metastatic disease in 9 cases (33.3%). Four patients who did not have a preoperative PET-CT were found to have metastatic disease at operation (9.7%). This equated to a total metastatic incidence of 26.5% in those who had been initially deemed resectable based on CT scan alone. The time interval from MDM decision to surgery averaged 25.4 days in those who did not have a PET/CT compared to 40.43 days in those who did. This was an average delay of 15.07 days until treatment. Conclusions This study demonstrates the important role the PET-CT has in the management of patients with pancreatic cancer. A significant number of patients avoided an unnecessary operation which would have delayed the commencement of chemotherapy. However, there are limitations to PET-CT, demonstrated in the patient with an inconclusive result, who was found to have liver metastases at surgery. The introduction of PET-CT in the staging process does undoubtedly cause delays to surgical resection and a more streamlined pathway needs to be developed to limit the delay to curative treatment.

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Adjuvant and neoadjuvant treatment for pancreatic adenocarcinoma

Japanese Journal of Clinical Oncology ◽

10.1093/jjco/hyaa018 ◽

2020 ◽

Vol 50 (5) ◽

pp. 483-489 ◽

Cited By ~ 4

Author(s):

Fuyuhiko Motoi ◽

Michiaki Unno

Keyword(s):

Pancreatic Cancer ◽

Adjuvant Chemotherapy ◽

Neoadjuvant Therapy ◽

Pancreatic Adenocarcinoma ◽

Multidisciplinary Treatment ◽

Neoadjuvant Treatment ◽

Neoadjuvant Chemoradiotherapy ◽

Disease Free Survival ◽

Promising Alternative ◽

Resectable Disease

Abstract The prognosis of pancreatic adenocarcinoma is dismal. Hence, advances in multidisciplinary treatment strategies, including surgery, are urgently needed. Early recurrence of distant organ metastases suggests that there are occult metastases even in cases with resectable disease. Several randomized controlled trials on adjuvant chemotherapy have been conducted to prolong survival after resection. CONKO-001 study was the first to demonstrate significant improvement in disease-free survival after surgery with gemcitabine administration. The JASPAC-01 study showed the superiority of adjuvant S1 over gemcitabine in survival after resection. Based on the results, adjuvant S1 therapy is the prescribed standard of care in Japan. Recently, the PRODIGE 24/CCTG PA.6 study showed that survival of patients treated with a modified FOLFIRINOX regimen as adjuvant therapy was significantly longer than those treated with adjuvant gemcitabine therapy. Although the evidence from these trials on adjuvant chemotherapy have been the gold-standard treatment for curatively resected and fully recovered patients, resectable disease at diagnosis is not the status, resected disease after curative resection. Currently, neoadjuvant therapy is considered to be a promising alternative to surgery for pancreatic cancer. Although there are many reports regarding neoadjuvant chemoradiotherapy, so far there has been no solid evidence proving the advantage of this strategy versus standard up-front surgery. Newly obtained results from the Prep-02/JSAP05 randomized phase II/III study, comparing neoadjuvant therapy with up-front surgery, revealed significant improvement in overall survival with neoadjuvant chemotherapy by intention-to-treat analysis. Thus, neoadjuvant intervention might become a new standard strategy in cases undergoing planned resection for pancreatic cancer.

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The impact of histology (adenocarcinoma vs. SCC) on outcomes in nonmetastatic pancreatic cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.4_suppl.419 ◽

2019 ◽

Vol 37 (4_suppl) ◽

pp. 419-419

Author(s):

Joshua Gruhl ◽

Samual Roberts Francis ◽

Randa Tao ◽

Benjamin Lev Solomon ◽

Christopher Duane Nevala-Plagemann ◽

...

Keyword(s):

Pancreatic Cancer ◽

Subgroup Analysis ◽

Cox Regression ◽

Adenosquamous Carcinoma ◽

Metastatic Pancreatic Cancer ◽

Borderline Resectable ◽

Resectable Disease ◽

Unresectable Disease ◽

Kaplan Meier ◽

The Impact

419 Background: Outcomes in squamous cell carcinoma (SCC) of the pancreas are generally thought to be poor compared with adenocarcinoma; however, this has not been sufficiently demonstrated in prior studies. This is the first NCDB analysis of the prognostic role of SCC histology in non-metastatic pancreatic cancer. Methods: We analyzed patients with non-metastatic pancreatic cancer using the National Cancer Database (NCDB) diagnosed from 2006-2014. Patients were analyzed according to histology—only adenocarcinoma, adenosquamous carcinoma, or SCC were selected for. The primary endpoint was overall survival (OS) from the time of diagnosis. Kaplan-Meier and Cox proportional hazard modeling were used to analyze OS. Results: A total of 94,928 patients were included; 94,016 in the adenocarcinoma group, 757 in the adenosquamous group, and 155 in the SCC group. There was a statistically significant decrease in median OS for patients with SCC (MS = 8.67 months, 95% CI: 7.23–9.92 months), compared to patients with adenosquamous carcinoma (MS = 12.7 months, 95% CI: 11.9–13.7 months) and adenocarcinoma (MS = 14.0 months, 95% CI: 13.86–14.06 months, p < .001). On multivariate Cox regression, both adenocarcinoma and adenosquamous carcinoma were associated with a longer OS compared with SCC (for adenocarcinoma, HR 0.45, 95% CI: 0.31–0.66, p < .001; for adenosquamous carcinoma, HR 0.60, 95% CI: 0.39–0.92, p = 0.02). On subgroup analysis, this OS improvement for adenocarcinoma histology was seen for patients with resectable/borderline resectable disease (HR 0.50, 95% CI: 0.32–0.79, p =.003) and for those with unresectable disease (HR 0.39, 95% CI: 0.19–0.77, p = 0.01). Conclusions: In patients with non-metastatic pancreatic cancer, there was a statistically significant detriment in OS for those with SCC histology compared with adenosquamous carcinoma or adenocarcinoma histology. On subgroup analysis, this difference persisted for those with resectable/borderline resectable disease and for those with unresectable disease. [Table: see text]

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Optimal Upfront Treatment in Surgically Resectable Pancreatic Cancer Candidates: A High-Volume Center Retrospective Analysis

Journal of Clinical Medicine ◽

10.3390/jcm10122700 ◽

2021 ◽

Vol 10 (12) ◽

pp. 2700

Author(s):

Sarah Maloney ◽

Malinda Itchins ◽

Jennifer Arena ◽

Sumit Sahni ◽

Viive M. Howell ◽

...

Keyword(s):

Pancreatic Cancer ◽

Neoadjuvant Chemotherapy ◽

Prognostic Markers ◽

Early Stage ◽

Cohort Analysis ◽

Cancer Center ◽

Resectable Pancreatic Cancer ◽

Treatment Pathways ◽

Resectable Disease ◽

Survival Difference

Pancreatic adenocarcinoma is a devastating disease with only 15–20% of patients resectable at diagnosis. Neoadjuvant chemotherapy for this cohort is becoming increasingly popular; however, there are no published randomized trials that support the use of neoadjuvant chemotherapy over upfront surgery in resectable disease. This retrospective cohort analysis was conducted to compare both treatment pathways and to identify any potential prognostic markers. Medical records from one large volume pancreatic cancer center from 2013–2019 were reviewed and 126 patients with upfront resectable disease were analyzed. Due to a change in practice in our center patients treated prior to December 2016 received upfront surgery and those treated after this date received neoadjuvant chemotherapy. Of these, 86 (68%) patients were treated with upfront surgery and 40 (32%) of patients were treated with neoadjuvant chemotherapy. Our results demonstrated that patients treated with upfront surgery with early-stage (1a) disease had a longer median OS compared to those treated with neoadjuvant chemotherapy (24 vs. 21 months, p = 0.028). This survival difference was not evident for all patients (regardless of stage). R0 resections were similar between groups (p = 0.605). We identified that both tumor viability (in neoadjuvant chemotherapy-treated patients) and tumor grade were useful prognostic markers. Upfront surgery for certain patients with low volume disease may be suitable despite the global trend towards neoadjuvant chemotherapy for all upfront resectable patients. A prospective clinical trial in this cohort incorporating biomarkers is needed to determine optimal therapy pathway.

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The Role of Staging Laparoscopy in Resectable and Borderline Resectable Pancreatic Cancer: A Systematic Review and Meta-Analysis

Digestive Surgery ◽

10.1159/000488372 ◽

2018 ◽

Vol 36 (3) ◽

pp. 251-260 ◽

Cited By ~ 7

Author(s):

Robert Ta ◽

Donal B. O’Connor ◽

Andrew Sulistijo ◽

Benjamin Chung ◽

Kevin C. Conlon

Keyword(s):

Pancreatic Cancer ◽

Meta Analysis ◽

Locally Advanced ◽

Staging Laparoscopy ◽

Resectable Pancreatic Cancer ◽

Borderline Resectable ◽

Resectable Disease ◽

Newcastle Ottawa Scale ◽

Resectable Cancer ◽

Additional Value

Aim: The study aimed to determine the additional value of staging laparoscopy in patients with pancreatic cancer deemed potentially resectable based on computed tomography imaging. Methods: A systematic literature search was performed using MEDLINE and the Cochrane Register of Controlled Trials (January 1995 to June 2017). Primary outcome measures were the overall yield and sensitivity to detect non-resectable disease. Quality of studies was assessed with the Newcastle-Ottawa Scale. Results: From 156 records, 15 studies including 2,776 patients met the inclusion criteria. In 12 studies, reporting outcomes on 1,756 patients with resectable disease after standard imaging, 350 (20%, range 14–38%) cases of non-resectable cancer were detected with staging laparoscopy. In 3 studies on 242 patients with locally advanced disease after standard imaging, staging laparoscopy detected metastases in 86 patients (36%). The failure rate of staging laparoscopy to detect non-resectable disease was 5% (64 of 1,406). Conclusion: Staging laparoscopy reduces the non-therapeutic laparotomy rate, and in locally advanced or borderline resectable disease, staging laparoscopy could more accurately select patients for neoadjuvant protocols.

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