ASO Author Reflections: Neoadjuvant Chemotherapy for Localized Pancreatic Ductal Adenocarcinoma—Predictors of Disease Progression and Performance Status Decline

Abstract Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal cancers. Known risk factors for this disease are currently insufficient in predicting mortality. The only FDA approved prognostic biomarker for PDAC patients is CA19-9. This, along with AJCC TNM staging and performance status, are considered important prognostic indicators in clinical practice. In order to better prognosticate patients with PDAC, we identified a novel panel of genes by utilizing publically available microarray and RNAseq data of PDAC tumors from GEO and TCGA. Expression of 20 genes were significantly associated with overall survival in four datasets and event-free survival in TCGA. A score generated based on the expression matrix of these genes could be validated in two independent cohorts. We find that this “Pancreatic cancer prognostic score 20 – PPS20” is dramatically elevated in metastatic tissue compared to primary tumor, and is higher in primary tumors compared to normal pancreatic tissue. Transcriptomic analyses show that tumors with low PPS20 have overall more immune cell infiltration and a higher CD8 T cell/Treg ratio when compared to those with high PPS20. Analyses of proteomic data from TCGA PAAD indicated higher levels of Cyclin B1, RAD51, EGFR and a lower E-cadherin/Fibronectin ratio in tumors with high PPS20. The PPS20 score defines not only prognostic and biological sub-groups but can predict response to targeted therapy options as well. Overall, PPS20 is a stronger and more robust transcriptomic signature when compared to similar, previously published gene lists.

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Complete Radiologic Response of Metastatic Pancreatic Ductal Adenocarcinoma to Microwave Ablation Combined with Second-Line Palliative Chemotherapy

Case Reports in Gastrointestinal Medicine ◽

10.1155/2020/4138215 ◽

2020 ◽

Vol 2020 ◽

pp. 1-7

Author(s):

Hakon Blomstrand ◽

Karin Adolfsson ◽

Per Sandström ◽

Bergthor Björnsson

Keyword(s):

Adjuvant Chemotherapy ◽

Pancreatic Ductal Adenocarcinoma ◽

Palliative Chemotherapy ◽

Lung Metastases ◽

Performance Status ◽

Progression Free Survival ◽

Disease Recurrence ◽

Ductal Adenocarcinoma ◽

Second Line ◽

First Line

Pancreatic ductal adenocarcinoma (PDAC) has a bleak prognosis, especially for the majority of patients diagnosed with metastatic disease. The primary option for palliative treatment is chemotherapy, and responses beyond first-line treatment are rare and typically short. Here, we report a case of a 63-year-old woman with PDAC in the head of the pancreas who was initially successfully treated by pancreaticoduodenectomy followed by adjuvant chemotherapy with gemcitabine. However, disease recurrence with liver and para-aortic lymph node metastases was detected only two months after the completion of adjuvant chemotherapy. First-line palliative chemotherapy with gemcitabine-nab/paclitaxel was commenced. The results were discouraging, with disease progression (liver and lung metastases) detected at the first evaluation; the progression-free survival was just two months (64 days). Surprisingly, the response to second-line palliative chemotherapy with 5-fluorouracil-oxaliplatin was excellent; in combination with the ablation of a liver metastasis, this treatment regimen resulted in a complete radiological response and an 11-month treatment-free interval with a sustained good performance status.

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Phase I/II Trial to Evaluate the Efficacy and Safety of Nanoparticle Albumin-Bound Paclitaxel in Combination With Gemcitabine in Patients With Pancreatic Cancer and an ECOG Performance Status of 2

Journal of Clinical Oncology ◽

10.1200/jco.18.00089 ◽

2019 ◽

Vol 37 (3) ◽

pp. 230-238 ◽

Cited By ~ 25

Author(s):

Teresa Macarulla ◽

Roberto Pazo-Cid ◽

Carmen Guillén-Ponce ◽

Rafael López ◽

Ruth Vera ◽

...

Keyword(s):

Phase I ◽

Pancreatic Ductal Adenocarcinoma ◽

Phase Ii ◽

Karnofsky Performance Status ◽

Performance Status ◽

Ductal Adenocarcinoma ◽

Tolerability Profile ◽

Ecog Performance Status ◽

Actuarial Survival ◽

Number Of Patients

Purpose Gemcitabine plus nanoparticle albumin-bound (NAB) paclitaxel (GA) significantly improved survival compared with gemcitabine alone in patients with metastatic pancreatic ductal adenocarcinoma (PDAC) and a Karnofsky performance status (PS) of 70% or greater. Because of the low number of patients with reduced PS, the efficacy of this regimen in fragile patients remains unclear. This study aimed to evaluate the efficacy and tolerability of different GA dosing regimens in patients with a poor PS. Patients and Methods In the phase I part of this study, patients were randomly assigned to one of the following four parallel GA treatment arms (six patients per arm): a biweekly schedule of NAB-paclitaxel (150 mg/m2 [arm A] or 125 mg/m2 [arm C]) plus gemcitabine 1,000 mg/m2 or a standard schedule of 3 weeks on and 1 week off of NAB-paclitaxel (100 mg/m2 [arm B] or 125 mg/m2 [arm D]) plus gemcitabine 1,000 mg/m2. The two regimens with the better tolerability profile on the basis of predefined criteria were evaluated in the phase II part of the study, the primary end point of which was 6-month actuarial survival. Results Arms B and D were selected for the phase II part of the study. A total of 221 patients (111 patients in arm B and 110 patients in arm D) were enrolled. Baseline characteristics including median age (71 and 68 years in arms B and D, respectively), sex (51% and 55% men in arms B and D, respectively), and metastatic disease (88% and 84% in arms B and D, respectively) were comparable between arms. The most frequent grade 3 or 4 toxicities in arms B and D were anemia (12% and 7%, respectively), neutropenia (32% and 30%, respectively), thrombocytopenia (7% and 11%, respectively), asthenia (14% and 16%, respectively), and neurotoxicity (11% and 16%, respectively). In arms B and D, there were no significant differences in response rate (24% and 28%, respectively), median progression-free survival (5.7 and 6.7 months, respectively), and 6-month overall survival (63% and 69%, respectively). Conclusion NAB-paclitaxel administered at either 100 and 125 mg/m2 in combination with gemcitabine on days 1, 8, and 15 every 28 days is well tolerated and results in acceptable safety and efficacy in patients with metastatic pancreatic ductal adenocarcinoma and a poor PS.

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Adjuvant chemotherapy after surgery for pancreatic ductal adenocarcinoma: retrospective real-life data

World Journal of Surgical Oncology ◽

10.1186/s12957-019-1732-3 ◽

2019 ◽

Vol 17 (1) ◽

Cited By ~ 7

Author(s):

Sophia Chikhladze ◽

Ann-Kathrin Lederer ◽

Lampros Kousoulas ◽

Marilena Reinmuth ◽

Olivia Sick ◽

...

Keyword(s):

Adjuvant Chemotherapy ◽

Pancreatic Ductal Adenocarcinoma ◽

Performance Status ◽

Real Life ◽

Disease Free Survival ◽

Biologically Active ◽

Ductal Adenocarcinoma ◽

Real Life Data ◽

Number Of Cycles

Abstract Background The recommendation for postoperative chemotherapy in pancreatic ductal adenocarcinoma (PDAC) is based on prospective randomized trials. However, patients included in clinical trials do not often reflect the overall patient population treated in clinical practice. Materials and methods A retrospective review of all patients undergoing pancreas resection for PDAC between 2001 and 2013 was performed. Follow-up data from oncologists, general practitioners, or hospital patient files were available for 92% of patients. Results A total of 251 patients were included in our analysis. Chemotherapy was recommended for 223 patients, but 86 patients did not follow the recommendation. The application of the recommended chemotherapy, consisting of 6 cycles of gemcitabine, was only applied to 45 patients. Forty patients received the recommended number of cycles with dose reduction or prolonged intervals between cycles, and adjuvant chemotherapy was terminated prior to the intended completion of all 6 cycles in 54 patients. Survival of patients after adjuvant chemotherapy was increased compared to that of patients without chemotherapy (with recurrence 25.6 vs. 14.3 months, p = 0.001, and without recurrence 27.4 vs. 14.3 months, p < 0.001). Terminating chemotherapy prior to completion (p = 0.009) as well as a lower number of chemotherapy cycles (p = 0.026) was associated with a decreased survival. Conclusion Adjuvant chemotherapy improves overall and disease-free survival after curative pancreatic resection, but only a small fraction of patients completes the recommended 6 cycles of adjuvant chemotherapy. Our data indicates that performance status of patients after pancreas resections for PDAC requires not only highly biologically active but also well-tolerated adjuvant chemotherapy regimens.

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Myosteatosis to predict postoperative morbidity in pancreatic ductal adenocarcinoma patients receiving neoadjuvant chemotherapy.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e16754 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e16754-e16754

Author(s):

Raphael Louie ◽

Gabriel Aleixo ◽

Allison Mary Deal ◽

Emily Damone ◽

Jaclyn Tremont-Portelli ◽

...

Keyword(s):

Neoadjuvant Chemotherapy ◽

Pancreatic Ductal Adenocarcinoma ◽

Postoperative Morbidity ◽

Tube Feeding ◽

Ct Scans ◽

Ductal Adenocarcinoma ◽

Baseline Body Mass Index ◽

Cross Sectional ◽

Student’S T ◽

Morbidity Risk

e16754 Background: Myosteatosis (adipose deposits in muscle) can be detected on cross-sectional imaging through variations in Skeletal Muscle Density (SMD). Patients with myosteatosis tend to have lower overall survival, increased chemotherapy toxicity, and shorter progression-free intervals across cancer types. We investigated whether changes in myosteatosis during neoadjuvant chemotherapy can predict postoperative morbidity risk in patients with pancreatic ductal adenocarcinoma (PDAC). Methods: This is a retrospective cohort study from 2014-2019 of patients with biopsy-proven PDAC who completed neoadjuvant chemotherapy and R0/1 resection (R1: margin < 1mm or microscopically positive). We obtained preoperative patient (age at diagnosis, baseline body mass index (BMI), sex, race, comorbidities) and treatment data (neoadjuvant chemotherapy regimen and duration, time from completion of systemic therapy to surgery, type of operation). Primary outcomes were postoperative complications and 90-day readmission. Average SMD was measured using imaging analysis software at the L3 level on axial abdominal CT scans at the time of diagnosis and at completion of neoadjuvant therapy (SliceOmatic TomoVision QC, Can). We defined SMDΔ as the decrease in SMD during neoadjuvant chemotherapy. Descriptive statistics and Student’s t-test were performed with STATA. Results: We identified 44 patients who received neoadjuvant chemotherapy, achieved a R0/1 resection, and had available CT scans for body composition evaluation. The postoperative complication rate was 43% (n = 19) and 90-day readmission rate was 30% (n = 13). Lower SMD at diagnosis was associated with increased postoperative delirium (p < 0.01) and 90-day readmission (p = 0.02). Greater SMDΔ was associated with increased ICU utilization (p < 0.01) and tube feeding upon discharge (p = 0.03). There was no significant association between preoperative BMI or albumin and our primary outcomes. Conclusions: Preoperative SMD and SMDΔ, rather than albumin or BMI, can predict postoperative morbidity in PDAC patients who received neoadjuvant chemotherapy. This study provides the framework for future studies to develop and validate a tool to predict postoperative morbidity risk in these patients.

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