Surgery After Response to Chemotherapy for Locally Advanced Pancreatic Ductal Adenocarcinoma: A Guide for Management

Because of the biologic aggressiveness and late presentation of pancreatic ductal adenocarcinoma (PDAC), up to 80% of patients have locally advanced or metastatic disease at presentation. The success of multiagent chemotherapy regimens in the management of metastatic disease has been translated to patients with locally advanced PDAC. Both FOLFIRINOX (fluorouracil/folinic acid/irinotecan/oxaliplatin) and gemcitabine/nab-paclitaxel are used to downstage locally advanced PDAC to render it eligible for resection with curative intent. This paradigm shift has significantly expanded the pool of patients who are eligible for resection with curative intent. However, the generalizability of present studies and the patient selection process are unclear. This article provides an evidence-based review of patient selection considerations and management algorithms, and details our institution’s approach to patients with locally advanced PDAC after preoperative chemotherapy.

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Pancreatic ductal adenocarcinoma from a surgical perspective

International Journal of Cancer Research & Therapy ◽

10.33140/ijcrt.06.02.13 ◽

2021 ◽

Vol 6 (2) ◽

Keyword(s):

Risk Factors ◽

Pancreatic Ductal Adenocarcinoma ◽

Adjuvant Treatment ◽

Locally Advanced ◽

Historical Background ◽

Ductal Adenocarcinoma ◽

Curative Intent ◽

Pancreatic Cancers ◽

Operative Care ◽

Histological Staging

Pancreatic ductal adenocarcinoma (PDAC) accounts for more than 90% of pancreatic cancers. Whilst most patients present with locally advanced or metastatic disease, a minority are candidates for curative-intent resection. This review covers the aspects of PDAC which are relevant to the surgeon. Firstly, an up-to-date overview of epidemiology, risk factors and pathogenesis are provided. Secondly, presentation, diagnosis and staging are covered, including a summary of the most recent staging guidelines. The review will then focus on the historical background of the pancreatico-duodenectomy (PD), the modern procedure and post-operative care. Finally, short sections provide the reader with an update on histological staging and adjuvant treatment.

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Homologous Recombination Deficiency in Patients With Pancreatic Ductal Adenocarcinoma and Response to Chemotherapy

JCO Precision Oncology ◽

10.1200/po.17.00087 ◽

2018 ◽

pp. 1-11 ◽

Cited By ~ 5

Author(s):

Safi Shahda ◽

Kirsten M. Timms ◽

Ashley A. Ibrahim ◽

Julia E. Reid ◽

Harvey M. Cramer ◽

...

Keyword(s):

Homologous Recombination ◽

Pancreatic Ductal Adenocarcinoma ◽

Locally Advanced ◽

Progression Free Survival ◽

Needle Aspiration ◽

Response To Therapy ◽

Ductal Adenocarcinoma ◽

Response To Chemotherapy ◽

Formalin Fixed Paraffin Embedded ◽

Mutation Data

Purpose Mutations or copy number abnormalities of genes involved in homologous recombination (HR) occur in pancreatic ductal adenocarcinoma (PDAC). DNA-based measures of HR deficiency (HRD) have been developed and may help identify tumors with better response to DNA-damaging agents. This study aimed to describe the HR pathway mutations and HRD status and determine their association with treatment response and outcome in patients with PDAC. Patients and Methods We performed a retrospective analysis of tumor samples from patients treated at Indiana University for locally advanced or metastatic PDAC. Patients were included if they received gemcitabine plus nanoparticle albumin-bound paclitaxel (control) or fluorouracil, oxaliplatin, leucovorin, and irinotecan (FOLFIRINOX) and had adequate follow-up to assess survival and response to therapy. Tumor analysis generated a three-biomarker HRD score and mutation data for 44 genes. Results Ninety-one samples met inclusion criteria, and 78 samples (formalin-fixed paraffin-embedded, n = 15; fine-needle aspiration, n = 63) generated mutation data. HRD analysis was successful for 57 samples (HRD score: median, 18; range, 5 to 61); the primary cause of failure was low tumor cellularity. Six BRCA1/ 2 mutations were detected, four with HRD scores in the top decile ( P = .011). There was no statistically significant correlation between HRD score and radiographic response (odds ratio per interquartile range, 1.40; P = .32 adjusted for treatment) in either treatment group. In patients treated with FOLFIRINOX, HRD score dichotomized at the median was not associated with progression-free survival (median, 5.3 v 9.4 months for low v high HRD score, respectively; P = .083) or overall survival (median, 11.9 v 10.7 months for low v high HRD score, respectively; P = .76). Conclusion Mutations in DNA repair genes occur in PDAC, and HRD scores can be generated in the majority of patients. The HRD score was not significantly associated with higher response rate or prolonged survival in patients treated with FOLFIRINOX.

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Intraoperative Peritoneal Washing Cytology on Survival in Pancreatic Ductal Adenocarcinoma With Resectable, Locally Advanced, and Metastatic Disease

Pancreas ◽

10.1097/mpa.0000000000001266 ◽

2019 ◽

Vol 48 (4) ◽

pp. 519-525 ◽

Cited By ~ 1

Author(s):

Zi Yin ◽

Tingting Ma ◽

Sheng Chen

Keyword(s):

Pancreatic Ductal Adenocarcinoma ◽

Metastatic Disease ◽

Locally Advanced ◽

Ductal Adenocarcinoma ◽

Peritoneal Washing ◽

Peritoneal Washing Cytology

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First line gemcitabine and nab-paclitaxel chemotherapy for localized pancreatic ductal adenocarcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.4_suppl.369 ◽

2018 ◽

Vol 36 (4_suppl) ◽

pp. 369-369

Author(s):

Pat Gulhati ◽

Laura Prakash ◽

Matthew H. G. Katz ◽

Xuemei Wang ◽

Milind M. Javle ◽

...

Keyword(s):

Pancreatic Ductal Adenocarcinoma ◽

Metastatic Disease ◽

Locally Advanced ◽

Standard Of Care ◽

Clinical Staging ◽

Ductal Adenocarcinoma ◽

First Line ◽

First Line Therapy ◽

Kaplan Meier ◽

Ecog Ps

369 Background: Chemotherapy is widely used as a component of treatment of localized pancreatic ductal adenocarcinoma (PDAC). Pre-operative chemotherapy is associated with early treatment of micro-metastases and guaranteed delivery of all components of multimodality therapy. For locally advanced (LA) PDAC, induction chemotherapy is standard of care. We evaluated the use of gemcitabine and nab-paclitaxel (Gem/nab-P) as first-line therapy in localized PDAC. Methods: Records of pts with localized PDAC who initiated Gem/nab-P at a single institution from 2013-2015 were retrospectively reviewed. Clinicopathologic features, dose and outcomes were evaluated. Pts were staged using our previously published criteria: potentially resectable (PR), borderline type A (BR-A) (anatomy amenable to vascular resection), BR-B (biology suspicious for metastatic disease including high CA19-9), BR-C (co-morbidities requiring medical optimization), and LA. Co-morbidities were classified using adult comorbidity evaluation-27 score. Overall survival (OS) was analyzed using Kaplan Meier method. Results:99 pts [M/F: 50/49; median age: 70 yrs (range 30-85); PR/BR/LA: 45/14/40] were treated with Gem/nab-P. Clinical staging showed PR+BR-A/BR-B+C: 20/39. BR-B+C included one or more of the following factors: age ≥80 yrs [13%], ECOG PS ≥2 [13%], moderate/severe co-morbidities [55%], CA19-9≥1000 [28%], suspicion for metastatic disease [21%]. Majority of pts received biweekly Gem/nab-P dosing [standard/biweekly/other: 10/80/9] with minimal grade 4 toxicity. 45/99 pts received chemoradiation after Gem/nab-P [30Gy/50.4Gy: 15/30]. 12/20 (60%) PR+BR-A, 2/39 (5%) BR-B+C and 1/40 (3%) LA pts underwent pancreatectomy. 13/15 resected pts received adjuvant chemotherapy. At median follow-up of 26 mo, median OS was 18 (95% CI: 15.6-20.5) mo for all, 17 (95% CI: 14.6-19.5) mo for unresected and not reached for resected pts (p = 0.03). Conclusions: A significant number of pts with resectable PDAC albeit aggressive biology (BR-B) and/or medically inoperable disease (BR-C) received first-line Gem/nab-P; resection rates were lower compared to PR/BR-A pts. Biweekly dosing is being used in localized PDAC and is well tolerated.

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Correlation Between the Acquisition of Resistance to Gemcitabine Therapy and the Expression of HuR in Pancreatic Ductal Adenocarcinoma: A Case Report

International Surgery ◽

10.9738/intsurg-d-15-00278.1 ◽

2019 ◽

Vol 103 (1-2) ◽

pp. 116-120

Author(s):

Atsushi Oba ◽

Daisuke Ban ◽

Atsushi Kudo ◽

Susumu Kirimura ◽

Hiromitsu Ito ◽

...

Keyword(s):

Partial Response ◽

Ct Scan ◽

Pancreatic Ductal Adenocarcinoma ◽

Abdominal Wall ◽

Present Report ◽

Locally Advanced ◽

Carbohydrate Antigen ◽

High Serum ◽

Ductal Adenocarcinoma ◽

Response To Chemotherapy

Recently, several studies have revealed the usefulness of biomarkers to predict the response to chemotherapy for pancreatic ductal adenocarcinoma (PDAC). Among them, human antigen R (HuR) is reported as a powerful marker for response to gemcitabine chemotherapy for PDAC. The present report describes a patient with PDAC who underwent gemcitabine therapy before resection and after recurrence, and HuR expression was examined at multiple stages. A 72-year-old man was diagnosed with locally advanced unresectable PDAC invading the common hepatic artery. After 9 cycles of gemcitabine treatment, a computed tomography (CT) scan demonstrated a partial response. He underwent distal pancreatectomy with portal vein resection. The pathologic assessment for response to the chemotherapy was grade Ib by Evans's criteria, and HuR expression was high. Serum carbohydrate antigen 19-9 (CA19-9) level rose rapidly at 4 months after the first resection. A CT scan and needle biopsy revealed a solitary recurrence in the abdominal wall, and HuR expression remained high. After 4 cycles of gemcitabine and S-1 combination therapy, a CT scan demonstrated a partial response, and serum CA19-9 decreased. However, after 2 additional cycles of the therapy, a CT scan demonstrated progressive disease, and serum CA19-9 increased slightly. By laparotomy, an abdominal wall recurrence and multiple peritoneal dissemination were found. HuR expression in the biopsy specimen obtained during the laparotomy was decreased. Although gemcitabine therapy was reinitiated, the disease progressed rapidly so the treatment was stopped. In this case, a correlation between the acquisition of resistance to gemcitabine therapy and change in HuR expression was demonstrated.

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Pancreatic ductal adenocarcinoma in colonic wall: metastatic disease or cancerized pancreatic ectopic tissue?

Surgical Case Reports ◽

10.1186/s40792-020-00846-5 ◽

2020 ◽

Vol 6 (1) ◽

Author(s):

Graziana Gallo ◽

Alessandro Mangogna ◽

Gianrocco Manco ◽

Stefania Caramaschi ◽

Tiziana Salviato

Keyword(s):

Pancreatic Ductal Adenocarcinoma ◽

Metastatic Disease ◽

Ductal Adenocarcinoma ◽

Colonic Wall ◽

Ectopic Tissue

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Management of Patients with Pancreatic Ductal Adenocarcinoma in the Real-Life Setting: Lessons from the French National Hospital Database

Cancers ◽

10.3390/cancers13143515 ◽

2021 ◽

Vol 13 (14) ◽

pp. 3515

Author(s):

Christelle de la Fouchardière ◽

Mustapha Adham ◽

Anne-Marie Marion-Audibert ◽

Antoine Duclos ◽

Claude Darcha ◽

...

Keyword(s):

Pancreatic Ductal Adenocarcinoma ◽

Real Life ◽

Ductal Adenocarcinoma ◽

University Hospitals ◽

National Hospital ◽

Curative Intent ◽

The Real ◽

Oncological Treatment ◽

Real Life Setting ◽

Number Of Patients

Pancreatic ductal adenocarcinoma (PDAC) remains a major public health challenge, and faces disparities and delays in the diagnosis and access to care. Our purposes were to describe the medical path of PDAC patients in the real-life setting and evaluate the overall survival at 1 year. We used the national hospital discharge summaries database system to analyze the management of patients with newly diagnosed PDAC over the year 2016 in Auvergne-Rhône-Alpes region (AuRA) (France). A total of 1872 patients met inclusion criteria corresponding to an incidence of 22.6 per 100,000 person-year. Within the follow-up period, 353 (18.9%) were operated with a curative intent, 743 (39.7%) underwent chemo- and/or radiotherapy, and 776 (41.4%) did not receive any of these treatments. Less than half of patients were operated in a high-volume center, defined by more than 20 PDAC resections performed annually, mainly university hospitals. The 1-year survival rate was 47% in the overall population. This study highlights that a significant number of patients with PDAC are still operated in low-volume centers or do not receive any specific oncological treatment. A detailed analysis of the medical pathways is necessary in order to identify the medical and territorial determinants and their impact on the patient’s outcome.

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Predicting Surgical Margins in Patients With Borderline Resectable and Locally Advanced Pancreatic Cancer Undergoing Resection

The American Surgeon ◽

10.1177/00031348211011129 ◽

2021 ◽

pp. 000313482110111

Author(s):

Weizheng Ren ◽

Dimitrios Xourafas ◽

Stanley W. Ashley ◽

Thomas E. Clancy

Keyword(s):

Pancreatic Ductal Adenocarcinoma ◽

Univariate Analysis ◽

Locally Advanced ◽

Advanced Pancreatic Cancer ◽

Ductal Adenocarcinoma ◽

Resection Margins ◽

Borderline Resectable ◽

Stepwise Selection ◽

R1 Resection ◽

Positive Resection Margins

Background Many patients with borderline resectable/locally advanced pancreatic ductal adenocarcinoma (borderline resectable [BR]/locally advanced [LA] pancreatic ductal adenocarcinoma [PDAC]) undergoing resection will have positive resection margins (R1), which is associated with poor prognosis. It might be useful to preoperatively predict the margin (R) status. Methods Data from patients with BR/LA PDAC who underwent a pancreatectomy between 2008 and 2018 at Brigham and Women’s Hospital were retrospectively reviewed. Logistic regression analysis was used to evaluate the association between R status and relevant preoperative factors. Significant predictors of R1 resection on univariate analysis ( P < .1) were entered into a stepwise selection using the Akaike information criterion to define the final model. Results A total of 142 patients with BR/LA PDAC were included in the analysis, 60(42.3%) had R1 resections. In stepwise selection, the following factors were identified as positive predictors of an R1 resection: evidence of lymphadenopathy at diagnosis (OR = 2.06, 95% CI: 0.99-4.36, P = .056), the need for pancreaticoduodenectomy (OR = 3.81, 96% CI: 1.15-15.70, P = .040), extent of portal vein/superior mesenteric vein involvement at restaging (<180°, OR = 3.57, 95% CI: 1.00-17.00, P = .069, ≥180°, OR = 7,32, 95% CI: 1.75-39.87, P = .010), stable CA 19-9 serum levels (less than 50% decrease from diagnosis to restaging, OR = 2.27, 95% CI: 0.84-6.36 P = .107), and no preoperative FOLFIRINOX (OR = 2.17, 95% CI: 0.86-5.64, P = .103). The prognostic nomogram based on this model yielded a probability of achieving an R1 resection ranging from <5% (0 factors) to >70% (all 5 factors). Conclusions Relevant preoperative clinicopathological characteristics accurately predict positive resection margins in patients with BR/LA PDAC before resection. With further development, this model might be used to preoperatively guide surgical decision-making in patients with BR/LA PDAC.

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