Adjuvant Chemoradiation Therapy for Adenocarcinoma of the Distal Pancreas
Department of Radiation Oncology and Molecular Radiation Sciences, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. Annals of Surgical Oncology
(Impact Factor: 3.93).
12/2010; 17(12):3112-9. DOI: 10.1245/s10434-010-1200-3
This study was designed to examine the effect of adjuvant 5-FU-based chemoradiation therapy (CRT) after distal pancreatectomy for adenocarcinoma of the distal pancreas.
All patients underwent curative resection for adenocarcinoma of the distal pancreas between December 1985 and June 2006. Patients who received adjuvant CRT were compared with those who underwent surgery alone. A Kaplan-Meier estimate of the survival curve was used to determine estimates of the median survival and proportion alive at 1 and 2 years; log-rank tests were used to make comparisons between groups.
A total of 123 patients underwent distal pancreatectomy; 29 patients were excluded for distant metastases at the time of surgery (n = 12, 10%) or before adjuvant therapy (n = 11, 9%), death within 2 months of surgery (n = 2, 2%), or if CRT treatment status was unknown (n = 4, 3%). Of the remaining 94 patients, 72% received adjuvant 5-FU-based CRT and 28% underwent surgery alone. Overall median survival was 16.2 (95% confidence interval (CI), 13.1-18.9) months. The groups were similar with respect to tumor size, nodal status, and margin status. There was no significant difference in overall survival between patients treated with adjuvant CRT versus surgery alone (p = 0.23). An exploratory subgroup analysis suggested a potential survival benefit of adjuvant CRT in patients with lymph node metastases (16.7 vs. 12.1 months, p < 0.01).
Adjuvant CRT did not increase survival compared with surgery alone; however, patients with node-positive disease appear to benefit from adjuvant CRT.
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ABSTRACT: Pancreatic cancer is a major cause of cancer-related mortality worldwide. Little progress has been made in improving outcomes over the past 3 decades despite numerous trials encompassing many therapeutic agents and modalities. Except for rare anecdotes, pancreatic cancer is only curable when resection is undertaken. Unfortunately, more than 80% of patients are not resectable with either locally advanced/unresectable or metastatic disease at presentation. In the small percentage of patients who are resected, approximately 20% will survive 5 years, indicating that even ‘‘curative’’ therapy is ultimately palliative in nature. 1 5-fluorouracil (5-FU) stood as the backbone of systemic therapeutic regimens in this disease for many years until 1997 when gemcitabine was shown to result in a modest (median 1.3-month) survival benefit over 5-FU in patients with advanced disease. With a corresponding improvement in quality of life measures in patients receiving gemcitabine, this was considered the first major advance in this disease in more than a decade. 2 Most patients with resectable disease will develop distant metastases and/or local recurrence following resection. Patterns of failure analyses from contemporary randomized trials have also demonstrated that resected patients, when treated with adjuvant chemotherapy only, experience unacceptably high rates of local recurrence. Therefore, it is reasonable to consider adjuvant therapies directed toward locally persistent disease, namely radiation therapy. In resectable patients, significant debate has arisen in recent years regarding the role of adjuvant radiation therapy, with widely diverging approaches. Both a small randomized trial as well as large institutional experiences from the United States have demonstrated a survival benefit in patients receiving adjuvant radiation therapy following pancreatic cancer resection. 3,4 In contrast, a study from the EORTC did not confirm a significant survival benefit from adjuvant radiation therapy and chemotherapy. 5 In addition, a large study from the ESPAC group (ESPAC-1) did not confirm radiation therapy benefit and in fact suggested a detriment to its use, reporting that any survival benefit from adjuvant therapy comes from systemic therapy with 5-FU. 6 This trial has been appropriately criticized for significant methodologic weaknesses, while still confirming that local recurrence remains a dominant form of failure in patients treated in this study. In a follow-up study from the ESPAC group (and in contrast to previously reported findings in advanced disease), preliminary results of the ESPAC-3 study showed that adjuvant gemcitabine did not confer any survival advantage when compared with the historical standard 5-FU. 7 A phase III study from the RTOG (9704) compared adjuvant gemcitabine delivered before and following 5-FU based chemoradiotherapy with a similar regimen using 5-FU before and following the same chemoradiotherapy regimen. 8 This study contained a greater number of distal pancreatic cancer patients versus other trials and analyzed outcomes between proximal and distal lesions. While the original report described a survival benefit in pancreatic head patients receiving adjuvant gemcitabine-based therapy, no survival advantage was seen with gemcitabine use in patients with body and tail lesions. While these randomized trials have included and focused on outcomes in patients with pancreatic head adenocarcinoma, a minority of patients (15–20%) will present with pancreatic body or tail lesions. Because these tumors are less common, little data exist describing outcomes and patterns of failure compared with patients with pancreatic head lesions. It is also unclear whether there are distinct biological differences between proximal and distal pancreatic tumors. Historically, patients with distal tumors have a worse prognosis compared with pancreatic head
Annals of Surgical Oncology 09/2010; 17(12):3082-4. DOI:10.1245/s10434-010-1356-x · 3.93 Impact Factor
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ABSTRACT: Substantial progress has been made in our understanding of the biology of pancreatic cancer, and advances in patients' management have also taken place. Evidence is beginning to show that screening first-degree relatives of individuals with several family members affected by pancreatic cancer can identify non-invasive precursors of this malignant disease. The incidence of and number of deaths caused by pancreatic tumours have been gradually rising, even as incidence and mortality of other common cancers have been declining. Despite developments in detection and management of pancreatic cancer, only about 4% of patients will live 5 years after diagnosis. Survival is better for those with malignant disease localised to the pancreas, because surgical resection at present offers the only chance of cure. Unfortunately, 80-85% of patients present with advanced unresectable disease. Furthermore, pancreatic cancer responds poorly to most chemotherapeutic agents. Hence, we need to understand the biological mechanisms that contribute to development and progression of pancreatic tumours. In this Seminar we will discuss the most common and deadly form of pancreatic cancer, pancreatic ductal adenocarcinoma.
The Lancet 05/2011; 378(9791):607-20. DOI:10.1016/S0140-6736(10)62307-0 · 45.22 Impact Factor
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ABSTRACT: The radical antegrade modular pancreatosplenectomy (RAMPS) procedure is a modification of standard distal pancreatosplenectomy. It was designed to provide the operative approach developed for cancers of the head of the pancreas to cancers of the body and tail of the pancreas, particularly with respect to the extent of node dissection and emphasis on obtaining microscopically negative tangential margins. The purpose of this report is to provide long-term survival results.
Forty-seven patients had RAMPS between 1999 and 2008. The decision to perform anterior vs posterior RAMPS was based on the position of the tumor as assessed by preoperative computed tomograms. Patients were entered in a prospective database and followed at intervals.
Thirty-two patients had anterior RAMPS and 15 had posterior RAMPS. Twenty-four patients had resection of 33 organs in addition to the left adrenal gland in the posterior RAMPS. Specimens were inked in the operating room. Mean tumor size was 4.4 cm. Negative tangential margins were obtained in 89% of specimens. Overall, the R0 rate was 81%. Mean lymph node count was 18. There were no 30-day or in-hospital mortalities. Mean and median follow-up times of living patients were 44.4 and 26.4 months. Median survival was 26 months and 5-year overall actuarial survival was 35.5%. The actual survival of 23 patients whose surgery was performed more than 5 years before the time of analysis was 30.4%.
RAMPS is associated with high negative tangential margin rates and very satisfactory survival rates for this aggressive tumor.
Journal of the American College of Surgeons 01/2012; 214(1):46-52. DOI:10.1016/j.jamcollsurg.2011.10.008 · 5.12 Impact Factor
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