Perioperative chemotherapy is associated with a survival advantage in early stage adenocarcinoma of the pancreatic head

doi:10.1016/j.surg.2016.05.029

Surgery

Volume 160, Issue 3, September 2016, Pages 714-724

Presented as an oral presentation at the 11th Annual Academic Surgical Congress in Jacksonville, FL, February 2–4, 2016.

https://doi.org/10.1016/j.surg.2016.05.029 Get rights and content

Background

The value of neoadjuvant chemotherapy in the treatment of early stage pancreatic cancer is not yet clear.

Methods

We evaluated patients from the National Cancer Data Base who underwent pancreaticoduodenectomy for clinical stage I and II pancreatic adenocarcinoma between 2006 and 2012.

Results

In total, 7,881 patients were identified. Of these, 27.5% received no chemotherapy, 57.4% received adjuvant chemotherapy, 10.2% received neoadjuvant chemotherapy alone, and 4.9% received perioperative chemotherapy, both preoperative and postoperative chemotherapy. Neoadjuvant chemotherapy use (neoadjuvant chemotherapy alone and perioperative chemotherapy) increased from 12.0% in 2006 to 20.2% in 2012. Patients who received chemotherapy prior to the operation (neoadjuvant chemotherapy alone and perioperative chemotherapy) had greater rates of margin negative (80.2% vs 73.0%, P < .001) and node negative (58.2% vs 28.7%, P < .001) resections and shorter mean durations of stay (12.0 vs 11.1 days, P = .012) than those receiving either adjuvant chemotherapy or no chemotherapy at all. There were no differences in 30-day unplanned readmissions (P = .074) and 90-day mortality (P = .227). On Cox survival analysis, adjusted for clinical variables including age and comorbid disease, patients undergoing perioperative chemotherapy, adjuvant chemotherapy, and neoadjuvant chemotherapy alone demonstrated significantly improved overall survival relative to that of patients undergoing resection alone (all P < .001). Patients receiving perioperative chemotherapy demonstrated a significant overall survival advantage compared with those receiving adjuvant chemotherapy (hazard ratio 0.75; 95% confidence interval, 0.65–0.85). Neoadjuvant chemotherapy alone had a marginal overall survival benefit compared with adjuvant chemotherapy (hazard ratio 0.89; 95% confidence interval, 0.81–0.98).

Conclusion

Early stage pancreatic cancer patients who receive perioperative chemotherapy have better overall survival than those receiving no chemotherapy, adjuvant chemotherapy, or neoadjuvant chemotherapy alone. Patterns of postoperative morbidity are similar regardless of the sequence of therapy. Neoadjuvant chemotherapy should be considered for patients presenting with early stage pancreatic cancer.

Section snippets

Data source

The National Cancer Data Base (NCDB), a joint project of the American Cancer Society and the American College of Surgeons’ Commission on Cancer (CoC), is a nationwide facility-based oncology dataset that currently captures 70% of all newly diagnosed cancers in the United States, annually reported from approximately 1,500 hospitals with CoC-accredited cancer programs.¹⁵ The NCDB includes only patients treated at facilities that are continuously accredited by the CoC.

Data are coded and reported

Results

We identified 7,881 patients who met the inclusion criteria: 3,083 (39.1%) were cStage I, and 4,798 (60.9%) were cStage II. Of these, 2,170 (27.5%) received no chemotherapy, 4,523 (57.4%) received ACT, 802 (10.2%) received NCTA, and 386 (4.9%) received PCT. The median age was 67 (range, 26–90), and most patients were white (84.6%), had Medicaid or Medicare (57.1%), and were treated at an academic facility (57.9%). In addition, 769 (64.7%) patients who received neoadjuvant chemotherapy (NCTA and

Discussion

The prognosis in all stages of pancreatic cancer is poor. Preoperative chemo/chemoradiotherapy has been proposed as a novel strategy to improve outcomes in patients presenting with resectable disease. We used the NCDB to examine the current data on the use of NCT in patients who seemed to have early stage, resectable disease at the time of diagnosis and who ultimately underwent successful resection. We observed an increasing trend in NCT utilization from 12% in 2006 to 20% in 2012. Young age,

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Locally advanced pancreatic cancer: Is surgical palliation associated with improved clinical outcome relative to medical palliation?
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The value of palliative surgery in pancreatic cancer is not well-defined.
We queried the National Cancer Database for patients undergoing curative-intent resection, palliative surgery or medical palliation for clinical stage cT4N0-2M0 pancreatic cancer. Cohorts were 1:1:1 propensity-score-matched for comorbidities and stage. Kaplan-Meier method was used to compare overall survival for matched cohorts.
9,107 patients met inclusion criteria: 3,567 (39 %) underwent curative intent surgery, 1608 (18 %) surgical palliation, 3932 (43 %) medical palliation. Patients undergoing resection and surgical palliation had significant hospitalizations (11.0 ± 0.4 vs. 10.0 ± 0.3 days; p = 0.821) and rates of readmission (8.1 % vs. 2.0 %; p < 0.001). Patients undergoing surgical palliation demonstrated marginal increases in survival relative to those undergoing medical palliation (8.54 vs. 7.36 months; p < 0.0001).
In patients undergoing care for locally advanced pancreatic cancer, palliative surgery is associated with marginal improvement in survival but significant lengths of hospitalization and risk of readmission.
Impact of Neoadjuvant Treatment and Minimally Invasive Surgery on Perioperative Outcomes of Pancreatoduodenectomy: an ACS NSQIP Analysis
2023, Journal of Gastrointestinal Surgery
There is an increasing use of neoadjuvant treatment (NAT) for pancreatic cancer (PC) followed by minimally invasive pancreatoduodenectomy (MIPD). We evaluate the impact of the surgical approach on 30-day outcomes in PC patients who underwent NAT.
Patients with PC who had NAT followed by MIPD or open pancreatoduodenectomy (OPD) were identified from a pancreatectomy-targeted dataset (2014–2020) of the National Surgical Quality Improvement Program. Comparisons were made between MIPD and OPD within NAT groups.
A total of 5588 patients were analyzed. Of those, 4907 underwent OPD and 476 underwent MIPD. In addition, 3559 patients received neoadjuvant chemotherapy alone and 1830 received neoadjuvant chemoradiation. In the chemotherapy-alone group, the MIPD subgroup had lower rates of any complication (38.2% vs. 45.8%, P = 0.005), but there were no differences in mortality (2.1% for MIPD vs 1.9% for OPD, P=0.8) or serious complication (11.8% for MIPD vs 15% for OPD, P=0.1). On multivariable analysis, MIPD was independently predictive of lower rates of any complication (OR: 0.74, 95% CI 0.6–0.93, P = 0.0009), CR-POPF (OR: 0.58, 95% CI 0.35–0.96, P = 0.04), and shorter LOS (estimate: −1.03, 95% CI −1.73 to −0.32, P = 0.004). In the chemoradiation group, patients undergoing MIPD had higher rates of preoperative diabetes (P < 0.05), but there were no significant differences in any outcomes between the two approaches in this group.
MIPD is safe and feasible after NAT. Patients having neoadjuvant chemotherapy alone followed by MIPD had lower rates of complications, shorter LOS, and fewer CR-POPFs compared to OPD.
Factors associated with inability to return to intended oncologic treatment in pancreatic cancer
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Return to Intended Oncologic Treatment (RIOT) has been proposed as a quality metric in the care of cancer patients. We sought to define factors associated with inability to RIOT in Pancreatic Ductal Adenocarcinoma (PDAC) patients.
The NCDB was queried for patients who underwent pancreaticoduodenectomy for pathologic stage IB, IIA, or IIB PDAC from 2010 to 2016. Multivariable binary logistic regression models identified factors associated with failure to RIOT, and Kaplan-Meier survival analysis and Cox multivariable regression models demonstrated the impact of failure to RIOT on survival.
Increasing age (p < .001), Hispanic race (p = .002), pathological stage IB (p = .004) and IIA (p = .001) as compared to IIB, increasing hospital stay (p < .001), and open surgical approach (p = .024) were associated with increased risk of inability to RIOT. Male sex (p < .001), Charlson-Deyo scores of 0 (p < .001) and 1 (p = .001) as compared to >2, negative surgical margins (p = .048), receiving care at academic institutions (p = .001), and increasing institutional case volume (p = .001) were associated with improved odds of RIOT.
Patient features can impact RIOT and should be considered when designing multi-modality treatment strategies.
Multi-specialty physician perspectives on barriers and facilitators to the use of neoadjuvant therapy for pancreatic ductal adenocarcinoma
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Citation Excerpt :
The delivery of chemotherapy and/or chemoradiation therapy prior to surgery, known as neoadjuvant therapy (NT), is increasingly utilized for patients with localized PDAC as it is for other cancer types as well.1,2 NT improves margin-negative resection rates, increases the receipt of multimodality therapy since a substantial proportion of patients undergoing pancreatectomy will be unable to initiate adjuvant chemotherapy, and based on emerging evidence from randomized controlled trials, leads to improved overall survival.3–9 For these reasons, NT is now the recommended approach for borderline resectable (BR) and locally advanced (LA) cancers and an acceptable option for potentially resectable (PR) cancers according to national guidelines.9–11
Neoadjuvant therapy (NT) is increasingly utilized for patients with localized pancreatic ductal adenocarcinoma (PDAC). Given the importance of completing multimodality therapy, the purpose of this qualitative study was to characterize physician perspectives on barriers and facilitators to delivering NT.
A purposive sample of surgical, medical, and radiation oncologists participated in semi-structured interviews. Interviews were transcribed and coded by 3 independent researchers, iteratively identifying themes until saturation was achieved.
Participants (n = 27) were heterogeneous in specialty, years of experience, practice setting, gender, and geography. The most commonly cited advantage of NT was the ability to downstage patients. The most commonly cited barriers included lack of access and limited evidence. Patient preference for immediate surgery was frequently cited as a barrier, but most participants felt that patients eventually understood the treatment recommendation after informed discussion. Recommendations to enhance the delivery of NT included improved patient education, communication, and better evidence.
In this qualitative study, indications for, barriers to, and opportunities to improve the delivery of NT for localized PDAC were identified. These results highlight the need for better evidence and protocol standardization for NT as well as methods of improving care coordination, communication, and education to improve patient-centered outcomes.
The impact of chemotherapy sequencing on resectable pancreatic cancer by stage
2022, Surgical Oncology
Citation Excerpt :
Nevertheless, there have been retrospective single-arm studies that support the use of NCT or PCT [16–18]. These studies not only show improved R0 resection rates but also survival [11,19,20]. One of the most recent evidence supporting preoperative chemotherapy is the preliminary results of a randomized controlled trial Prep-02/JSAP-05 from Japan conducted exclusively in resectable PDAC, showing a benefit for NCT using perioperative gemcitabine/S1 versus adjuvant SI [21].
While chemotherapy is an important therapeutic modality for pancreatic cancer (PDAC), the optimal sequence of chemotherapy to surgery remains unclear. Further, the precise added benefit of including chemotherapy at each (especially early) stage has not been quantified.
The National Cancer Database (NCDB) was queried for patients with PDAC who underwent pancreaticoduodenectomy between 2004 and 2016. Cox multivariable and Kaplan-Meier survival analyses were performed for disease-specific survival (DSS) and overall survival (OS) after correcting for confounders. Permutations of chemotherapy/surgery were compared: preoperative only (NCT), postoperative only (ACT), pre- and post-operative (perioperative, PCT), and no therapy (NoT).
22975 patients met inclusion criteria. 13944(61%) received ACT, 1793(8%) received NCT and 946(4%) received PCT, while 6292(27%) did not receive chemotherapy. Log-rank test showed inferior survival in the NoT group compared to NCT, ACT, and PCT. Compared to the NoT group, PCT had the lowest rate of death (HR 0.704, p < 0.001) followed by NCT (HR 0.721, p < 0.001) and ACT (HR 0.759, p < 0.001).).
PDAC patients receiving chemotherapy, independent of their stage, will result in better DSS and OS. NCT should be given consideration for resectable disease including early stage PDAC and ideally complemented with postoperative chemotherapy. While there was a trend towards improved survival for PCT, NCT and ACT are reasonable options for stages IB-III.
Recurrence after surgical resection of pancreatic cancer: the importance of postoperative complications beyond tumor biology
2021, HPB
Citation Excerpt :
Therefore, the identification of patient-related, tumor-related or strategy-related parameters associated with increased risk of tumor-recurrence is clinically very relevant. In recent years neoadjuvant treatment has been applied with increasing frequency in the setting of potentially resectable PDAC.6–8 Although neoadjuvant treatment may provide several advantages compared to adjuvant therapy, including early treatment of micro-metastases and increased R0/N0 resection rate, the only accepted indication for neoadjuvant therapy so far is the presence of a borderline resectable tumor due to vascular involvement.1,2
Current treatment of potentially resectable pancreatic ductal adenocarcinoma (PDAC) includes pancreatic resection followed by adjuvant therapy. Aim of this study is to identify factors that are related with overall and early recurrence after pancreatectomy for PDAC.
Retrospective analysis of patients with histologically confirmed PDAC who underwent pancreatectomy between September 2009 and December 2014. Early relapse was defined as recurrence within 12 months after surgery. Univariate/multivariate analysis was performed to identify prognostic factors for recurrence.
261 patients were included (54% males, mean age 67 years). Neoadjuvant and adjuvant treatments were performed in 55 (21%) and 243 (93%) patients. Overall morbidity was 56% with a rate of grade 3–4 Clavien–Dindo complications of 25%. Median disease-free survival was 18 months. Multivariate analysis identified nodal metastases (OR: 3.6) and perineural invasion (OR: 2.14) as independent predictors of disease recurrence in the entire cohort. 76 patients (29%) had an early recurrence. Poorly differentiated tumors (OR: 3.019) and grade 3–4 Clavien–Dindo complications (OR: 3.05) were independent risk factors for early recurrence.
Although overall recurrence is associated with tumor-related factors, severe postoperative complications represent an independent predictor of early recurrence. Patients at increased risk of severe postoperative complications may benefit from neoadjuvant therapy.

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Presented at the Academic Surgical Congress 2016Perioperative chemotherapy is associated with a survival advantage in early stage adenocarcinoma of the pancreatic head

Background

Methods

Results

Conclusion

Section snippets

Data source

Results

Discussion

J Am Coll Surg

HPB

J Gastro Surg

J Clin Epidemiol

J Gastro Surg

A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer

New Engl J Med

Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: A randomized controlled trial

JAMA

Fluorouracil vs gemcitabine chemotherapy before and after fluorouracil-based chemoradiation following resection of pancreatic adenocarcinoma: A randomized controlled trial

JAMA

Pancreatic cancer

New Engl J Med

Neoadjuvant therapy for pancreatic cancer: A current review

J Surg Oncol

Presented at the Academic Surgical Congress 2016
Perioperative chemotherapy is associated with a survival advantage in early stage adenocarcinoma of the pancreatic head