Dr. Blackstock and colleagues are to be commended for their concise
review broadly outlining current advances in the management of
pancreatic cancer and future avenues of development.
As noted by the authors, a significant obstacle to improving survival
remains the large percentage of patients presenting with advanced
disease at diagnosis. However, even patients with localized, resectable
disease have a 5-year survival rate of only 20% [1,2].
Locoregional failure remains the predominant mode of failure in
patients with localized tumors undergoing resection, as well as
in those with locally advanced disease. In 1990, Griffin et al
 reported the failure patterns of 36 patients who underwent
curative resection. Disease recurred in 72% of these patients
at a median of 8 months after surgery. Of patients who suffered
a failure, all had a component of intra-abdominal failure, 73%
failed locally, and 62% failed in the liver. Local control was
unaffected by more extensive surgical resection (Whipple resection
vs total pancreatectomy) but was improved in patients who received
adjuvant external- beam treatment more than 55 Gy (50% vs 25%).
Although external-beam irradiation given in conjunction with 5-fluorouracil
(5-FU) has improved median survival in patients with both resectable
 and locally advanced  disease, locoregional control remains
problematic. Other techniques discussed in the article (intraoperative
radiation therapy , interstitial brachytherapy ) have improved
local control but not survival. These approaches, however, did
not address other potential sites of intra-abdominal failure.
Recent Efforts to Improve Locoregional Control
In an attempt to improve locoregional control, recent efforts
not mentioned by the authors have focused on prophylactic hepatic
irradiation given in conjunction with localized chemoradiation.
The Medical College of Wisconsin  reported a trial of prophylactic
hepatic radiation (2,340 cGy) and localized pancreatic radiation
(6,120 cGy) plus bolus 5-FU (500 mg/m²/d given the first
3 days of weeks 1 and 5) in 16 patients with locally advanced
disease. Only two patients developed clinical recurrences in the
This finding prompted the Radiation Therapy Oncology Group 
to initiate a phase I/II trial in patients with unresectable pancreatic
carcinoma. Treatment consisted of continuous pancreatic radiation
(6,120 cGy) and simultaneous prophylactic hepatic irradiation
(2,340 cGy) given during the last 2½ weeks, combined with
continuous-infusion 5-FU (1,000 mg/m²/d for 5 days beginning
on days 1 and 30). Of the 79 patients evaluated, 2 died from treatment
complications while 9 developed life-threatening toxicity. Overall,
liver metastases were documented in 32% of patients and abdominal
dissemination in 27%. However, 73% developed persistent or progressive
tumor in the pancreas. The median survival of patients entered
into the trial was 8.4 months.
Evans et al  recently recounted their experience at M.D. Anderson
Cancer Center using a similar approach to treat 11 patients with
potentially resectable carcinoma of the pancreas. Patients received
external-beam radiation to the pancreas (5,040 cGy) and liver
(2,340 cGy) with continuous-infusion 5-FU (300 mg/m²/d).
Seven of nine patients who were restaged were taken to surgery.
Four underwent pancreaticoduodenectomy and received 10 Gy of intraoperative
electron-beam irradiation to the tumor bed, half of whom have
no evidence of disease 18 and 25 months after surgery. Five of
seven patients dying of disease had metastases to the liver. Two
patients died of treatment-related complications, prompting termination
of the study.
Improvements in Median Survival for Resected Patients
Although the outlook remains poor for the majority of patients
diagnosed with pancreatic carcinoma, improvements in median survival
have been reported for patients with localized tumors undergoing
resection. As reviewed by Blackstock et al, the Johns Hopkins
experience  of 201 patients undergoing pancreaticoduodenectomy
for carcinoma of the head of the pancreas between 1970 and 1994
showed significant improvements in median survival over the past
3 decades attributable to decreased operative mortality and increased
use of adjuvant chemoradiation. Of note, patients with negative
lymph nodes and negative resection margins had a median survival
of 32 months and a 5-year survival rate of 40%. Other reported
predictors of long-term survival included diploid tumor DNA content
and tumor diameter less than 3 cm.
In summary, advances in diagnostic technology have not appreciably
changed the percentage of patients diagnosed with localized, potentially
resectable disease. Although localized chemoradiation has improved
median survival in localized and advanced disease, local control
and intra-abdominal metastases remain significant impediments
to long-term survival. Recent trials of prophylactic hepatic irradiation
given with pancreatic chemoradiation for localized and advanced
disease have been disappointing to date. Methods to improve detection
of disease while resectable are needed. Until such methods are
available, we must continue clinical trials utilizing both current
and newer modalities.
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for locally unresectable pancreatic carcinoma. Ann Surg 189:205-208,
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