Adjuvant Chemoradiation Therapy After Pancreaticoduodenectomy in Elderly Patients With Pancreatic Adenocarcinoma

doi:10.1016/j.ijrobp.2010.04.003

International Journal of Radiation OncologyBiologyPhysics

Volume 80, Issue 5, 1 August 2011, Pages 1391-1397

Presented at the 49th Annual Meeting of the American Society for Therapeutic Radiology and Oncology (ASTRO), Los Angeles, California, 2007.

https://doi.org/10.1016/j.ijrobp.2010.04.003 Get rights and content

Purpose

To evaluate the efficacy of adjuvant chemoradiation therapy (CRT) for pancreatic adenocarcinoma patients ≥75 years of age.

Methods

The study group of 655 patients underwent pancreaticoduodenectomy (PD) for pancreatic adenocarcinoma at the Johns Hopkins Hospital over a 12-year period (8/30/1993 to 2/28/2005). Demographic characteristics, comorbidities, intraoperative data, pathology data, and patient outcomes were collected and analyzed by adjuvant treatment status and age ≥75 years. Cox proportional hazards analysis determined clinical predictors of mortality and morbidity.

Results

We identified 166 of 655 (25.3%) patients were ≥75 years of age and 489 of 655 patients (74.7%) were <75 years of age. Forty-nine patients in the elderly group (29.5%) received adjuvant CRT. For elderly patients, node-positive metastases (p = 0.008), poor/anaplastic differentiation (p = 0.012), and undergoing a total pancreatectomy (p = 0.010) predicted poor survival. The 2-year survival for elderly patients receiving adjuvant therapy was improved compared with surgery alone (49.0% vs. 31.6%, p = 0.013); however, 5-year survival was similar (11.7% vs. 19.8%, respectively, p = 0.310). After adjusting for major confounders, adjuvant therapy in elderly patients had a protective effect with respect to 2-year survival (relative risk [RR] 0.58, p = 0.044), but not 5-year survival (RR 0.80, p = 0.258). Among the nonelderly, CRT was significantly associated with 2-year survival (RR 0.60, p < 0.001) and 5-year survival (RR 0.69, p < 0.001), after adjusting for confounders.

Conclusions

Adjuvant therapy after PD is significantly associated with increased 2-year but not 5-year survival in elderly patients. Additional studies are needed to select which elderly patients are likely to benefit from adjuvant CRT.

Introduction

The expanding elderly population of the United States is creating new demands on the medical system to serve the elderly. Current estimates place the number of individuals in United States aged 65 or older at nearly 35 million, with approximately 47% of these individuals aged 75 or older (1). The elderly population is expected to grow by more than 50% by 2050. It has been estimated that the increase in the elderly population will account for up to a 51% increase in the number of patients undergoing oncologic procedures by 2020 (2).

Pancreatic adenocarcinoma is a common cancer, with an estimated 42,470 cases diagnosed in the United States in 2009 (3). The disease is highly lethal, with approximately 95% patients dying within 5 years of diagnosis (4). Although the incidence of pancreatic adenocarcinoma is stable overall, the incidence of disease increases dramatically with age (5). Given the aging population of the country, the prevalence of pancreatic cancer can be expected to increase over the next half century. In fact, according to Surveillance, Epidemiology, and End Results data, 32% of patients who are diagnosed with pancreatic adenocarcinoma are at least 75 years old (6).

Research into the management of pancreatic adenocarcinoma has shown that age itself is not a contraindication to surgery, with no differences in morbidity, mortality, or reoperation found between elderly and nonelderly patients (7). Among the oldest patients treated with pancreaticoduodenectomy (PD) for pancreatic adenocarcinoma, age has been found to contribute less than 1% to the outcome of death or a complication (8).

Most studies evaluating the tolerability of chemotherapy and radiation in elderly patients have been based on conventional outdated radiation delivery methods (9). More recent research suggests that radiation can be safely delivered to elderly patients and result in improved survival and quality of life 10, 11. We have found that adjuvant 5-fluorouracil (5-FU)-based chemoradiation therapy (CRT) results in improved survival (12). Whether this same benefit is maintained in elderly patients is unknown. Therefore, the purpose of this study was to evaluate the efficacy of adjuvant 5-FU-based CRT in elderly patients who underwent a curative resection for pancreatic cancer at the Johns Hopkins Hospital (JHH).

Section snippets

Patient selection

Approval for this study was granted by the Johns Hopkins Hospital Institutional Review Board before data collection. Between August 30, 1993 and February 28, 2005, data were prospectively collected on all patients undergoing elective pancreaticoduodenectomy or total pancreatectomy at JHH. Distal pancreatectomy alone, duodenal, ampullary, bile duct adenocarcinomas, cystic neoplasms, and neuroendocrine tumors were excluded. A single pathologist reviewed all pathology specimens to ensure

Patient demographics and tumor pathologic features

Patient demographic and tumor pathologic features are displayed in Table 1. The median age of nonelderly patients was 62.0 years (range, 34–74), and the median age of elderly patients was 79.0 years (range, 75–90; p < 0.001). Among nonelderly patients, 56.0% had comorbid diseases (hypertension, diabetes mellitus, chronic obstructive pulmonary disorder, or cardiovascular disease); 66.3% of elderly patients had these same comorbidities (p = 0.021). The presence of positive lymph nodes varied

Discussion

The appropriate use of adjuvant CRT in patients with resectable pancreatic cancer is controversial. The findings of the Gastrointestinal Tumor Study Group (GITSG) support the use of adjuvant chemoradiation (16). Two European Study Group for Pancreatic Cancer (ESPAC) trials have suggested a possible detrimental effect with adjuvant C)RT 17, 18, although these have been criticized for lack of quality control in the delivery of radiation. Our institution previously reported a benefit in median,

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Cited by (32)

An international comparison of treatment and short-term overall survival for older patients with pancreatic cancer
2019, Journal of Geriatric Oncology
Citation Excerpt :
A Dutch study [14] showed that over time resection rates increased in older patients in the Netherlands, and that despite higher short-term mortality, octogenarians who underwent pancreatic resection showed long-term survival similar to younger patients. Beyond surgery, the appropriate use of adjuvant chemoradiation in older patients is controversial [15]; a prospective randomized study showed a significant longer median survival in patients who received radiation and chemotherapy [16]. However, two randomized controlled trials (RCTs) showed no survival benefit [17,18].
A significant proportion of patients with pancreatic cancer are over the age of 70 years. The aim was to compare treatment and survival for older patients with pancreatic cancer treated throughout the Netherlands or Moffitt Cancer Center (Tampa, Florida).
All age-eligible patients with pancreatic adenocarcinoma (2008–2012) were identified. Results were stratified by stage. Treatment (neoadjuvant, surgery, adjuvant and palliative treatment) and short-term survival were compared, and where appropriate adjusted (sex, age, grade, year) or stratified according to age or hospital (Netherlands- academic, teaching, non-teaching).
In total, 2728 patients were included. Neo-adjuvant chemoradiation was more often administered at Moffitt (non-metastatic stages), as was adjuvant chemoradiation and chemotherapy (p < .001). The proportion surgery was not significantly different. In patients with advanced disease, more patients at Moffitt underwent palliative chemotherapy (64.5% versus 17.4%; p < .001). Short-term survival was better among Moffitt patients (HR 0.30 (95%CI 0.11–0.82), HR 0.56 (0.41–0.72), HR 0.43 (0.36–0.52) for early, T3 or node positive and advanced). Differences were less pronounced comparing Dutch academic hospitals to Moffitt.
In the present comparison, a treatment regimen as delivered at Moffitt was associated with prolonged short-term survival. Further detailed analyses of selection criteria for systemic treatment could lead to tailored treatment and improved outcomes.
Radiotherapy of pancreatic cancer in older patients: A systematic review
2019, Journal of Geriatric Oncology
Citation Excerpt :
One-year LC, PFS, MFS and OS of 26.6%, 18.2%, 27.1%, and 35.5%, respectively were reported in one study [8]. Two studies on adjuvant CRT reported five-year OS of 49.7% and 62.3%, respectively [6,12]. ( Table 1).
Pancreatic cancer (PaC) will soon be one of the main causes of cancer mortality. Furthermore, its incidence is higher in the older population and radiotherapy (RT) represents a treatment option. The aim of this review was to evaluate feasibility and outcome of RT in older patients with PaC. A systematic literature review of patients aged ≥65 years with PaC treated with RT was performed using the PRISMA methodology. Eleven papers (1830 patients) fulfilled our inclusion criteria and were analyzed. RT was prescribed either alone or as an adjuvant treatment. Prescribed RT dose ranged from 22.0 to 70.0 Gy with conventional fractionation or hypo-fractionated schedule and delivered by three-dimensional conformal RT, intensity modulated RT or stereotactic body RT. Grade ≥ 3 acute and grade ≥ 2 late toxicity rates ranged between 0.0% and 52.6% (median: 0.5%) and between 0.0% and 15.0% (median: 0%), respectively. Median overall survival and two-year survival rate were 11.3 months (range: 6.4–69.0 months) and 49.0% (range 6.6–75.5%), respectively.
RT in older patients seems to be tolerable and safe particularly in terms of late toxicity irrespective of the treatment settings. Therefore, RT can represent a treatment option in PaC even in an older population. Further analyses and prospective trials enrolling older patients are needed to better define the risk/benefit ratio in different treatment settings.
Potential role of surgical resection for pancreatic cancer in the very elderly
2015, Pancreatology
Citation Excerpt :
Although therapeutic benefit of chemotherapy, especially post-operative adjuvant therapy in the very elderly, is still widely unknown, a few retrospective studies suggest similar benefits of chemotherapy in physically fit elderly patients compared to younger patients [18,19]. There are few reports to address the efficacy of adjuvant therapy in elderly pancreatic cancer patients [20,32]. The elderly are susceptible to many distinct geriatric factors related to chemotherapy discontinuation.
There is increasing need to evaluate the surgical indication of pancreatic cancer in very elderly patients. However, the available clinical data are limited, and the optimal treatment is still controversial. The aim of this study was to evaluate the benefit of pancreatic resection in pancreatic cancer patients over the age of 80.
Between 2005 and 2012, 26 octogenarian patients who received pancreatic resection and 20 who received chemotherapy for pancreatic cancer were retrospectively reviewed. Clinicopathological factors, chemotherapy administration status, and survival were compared. Univariate and multivariate analysis of prognostic factors for survival was performed.
Postoperative major complication rate was 8%, with no mortality. The one-year survival rate and median survival time of the surgery and chemotherapy groups were 50% and 45%, and 12.4 months and 11.7 months, respectively (P = 0.263). Of the 26 resected cases, 6 completed the planned adjuvant chemotherapy treatment course. The median survival time of those 6 completed cases was significantly longer than that of the 20 not completed cases (23.4 versus 10.0 months, P = 0.034). Furthermore, a multivariate analysis of the 26 resected cases showed that distant metastasis (HR 3.206, 95%CI 1.005–10.22, P = 0.049) and completion of the planned adjuvant therapy (HR 4.078, 95%CI 1.162–14.30, P = 0.028) were independent prognostic factors of surgical resection.
Surgical resection was safe, but not superior to chemotherapy for pancreatic cancer in octogenarians. In the very elderly, only selected patients may benefit from pancreatic resection.
Resected pancreatic cancer outcomes in the elderly
2015, Journal of Geriatric Oncology
To determine if age affects outcome in patients with resected pancreatic head cancer.
An IRB-approved pancreatic cancer database was queried for patients with upfront resected pancreatic head cancer treated at our institution between 2000 and 2012. Overall survival (OS) curves were calculated according to the Kaplan–Meier method and log-rank analysis. Multivariate analysis was performed using the Cox proportional hazard model.
We identified 193 patients. Patients ≥ 70 years were less likely to receive adjuvant treatment (p = 0.002); however there were no other significant differences between age groups. There was a trend towards increased pancreatic leaks in the elderly group (p = 0.06), but no difference in post-operative complications or mortality. There was no difference in overall survival based on age. Median and 5-year OS were 23 months and 26.7% in patients < 70 years, 23.4 months and 23% in those 70–75 , 16.1 months and 0% in those 76–80, and 18.7 months and 15.4% in those > 80 years (p = 0.62). On univariate analysis, there was increased OS in patients with lower T stage, N0 status, post-operative CA19-9 level < 90, and use of chemoradiotherapy (p < 0.05). Multivariate analysis revealed that lower tumor stage, N0, post-operative CA19-9 level < 90, and use of any adjuvant therapy predicted decreased mortality (p < 0.05). Age, gender, tumor site, tumor grade, and positive margins were not prognostic on multivariate analysis.
There is no difference in outcomes when comparing elderly patients with resected pancreatic cancer to those patients < 70 years of age.
Diagnostic evaluation and staging of pancreatic ductal adenocarcinoma
2015, Seminars in Oncology
Pancreatic ductal adenocarcinoma (PDA) frequently presents at an advanced and incurable stage of the disease. Common signs and symptoms of PDA include abdominal or back pain, jaundice, weight loss, pruritus, and nausea/vomiting. Diagnostic workup includes serum chemistries and CA19-9, primarily to monitor disease status and response to treatment. Imaging studies are performed to assess resectability and stage disease, and pancreatic protocol computed tomography (CT) scan or magnetic resonance imaging (MRI) are the preferred imaging studies for this purpose. Conventional staging is based on the American Joint Cancer Committee (AJCC) Staging System, 7th Edition and informs prognosis, while surgical staging systems focus specifically on assessing the likelihood of a complete (negative margins) resection with operative management. Herein, we review the presenting signs and symptoms, the diagnostic evaluation, and staging of PDA.
Pancreatic Cancer
2015, Clinical Radiation Oncology

View all citing articles on Scopus

: The Sol Goldman Pancreatic Cancer Research Center.

: Conflict of interest: none.

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Clinical InvestigationAdjuvant Chemoradiation Therapy After Pancreaticoduodenectomy in Elderly Patients With Pancreatic Adenocarcinoma

Purpose

Methods

Results

Conclusions

Introduction

Section snippets

Patient selection

Patient demographics and tumor pathologic features

Discussion

J Am Coll Surg

Lancet

Gastroenterol Clin North Am

Ann Oncol

Ann Oncol

Projections of the total resident population by 5-year age groups and sex with special age categories: Middle series 2025 to 2045, 2050 to 2070

Workload projections for surgical oncology: Will we need more surgeons?

Ann Surg Oncol

Cancer Statistics, 2009

CA Cancer J Clin

The epidemiology of pancreatic cancer in the United States: Changes below the surface

Aliment Pharmacol Ther