Pancreatic cancer patients treated with a combination
of chemotherapy and radiation after
surgery survive approximately six months longer than those
receiving surgery alone, Johns
Hopkins Kimmel Cancer Center scientists report.
Clinical trials conducted in the 1980s and 1990s in
the United States established the benefit of
postoperative chemotherapy and radiation; however, experts
still disagree on whether to administer
the treatments because results from European studies
suggest the opposite effect — a decrease in
"Some physicians might avoid chemotherapy and
radiation if a benefit in survival is uncertain.
However, without proof, I believe it is a disservice to
these patients if we eliminate chemotherapy and
radiation," said radiation oncologist Joseph Herman, who
led the study.
Herman and his team sought to put the issue to rest by
reviewing records of 616 Johns Hopkins
patients whose pancreatic cancers were surgically removed
between Aug. 30, 1993, and Feb. 28, 2005.
The researchers compared the survival of 345 of the
patients who had only surgery with 271 who
were then treated with 5-fluorouracil (FU)-based
chemotherapy agents and modern types of radiation.
Patients receiving the combined chemotherapy and
radiation experienced an improved median
survival when compared with patients who did not (21.2 vs.
14.4 months). Two-year survival also
improved (43.9 percent vs. 31.9 percent), as did five-year
survival (20.1 percent vs. 15.4 percent).
Results are published in the July 20 issue of the
Journal of Clinical Oncology.
"The take-home message of this study is that patients
who received combined chemotherapy
and radiation appeared to have better survival than
patients who have surgery alone, suggesting that
it is safe and beneficial if it's done carefully and
properly," said Herman, assistant professor in the
School of Medicine's Department of Radiation Oncology and
Molecular Radiation Sciences.
Herman cautions that this is a retrospective study and
that selection bias was possible as the
physicians may have selected out those patients who were
healthy enough to receive the
chemotherapy and radiation. "Regardless, it is still
encouraging to say that many of these patients had
very aggressive cancer, and a lot of them are still alive
several years after they received this
combination therapy," he said.
Because data to assess treatment toxicity were
unavailable, Herman and his study team focused
instead on survival. The majority of patients were able to
complete the therapy, he says, suggesting
that they tolerated it well.
The study also identified risk factors to determine
those patients most likely to benefit from
combined chemotherapy and radiation. Patients who clearly
benefited included those with lymph nodeŠ
positive disease and those with tumors larger than 3
centimeters (about 1.2 inches). Patients with
aggressive tumors also benefited, as did those with
margin-positive disease, where the surgeon was
unable to remove most of the tumor.
Groups were similar with respect to tumor size, nodal
status and margin status, but those
receiving combined chemotherapy and radiation were younger
(median 64 years vs. 70 years) and less
likely to present with another serious disease.
"The survival benefit is still seen regardless of
high-risk tumor characteristics and after
controlling for age, other concurrent diseases and surgical
complications," Herman said.
Patients in this study received about five and a half
weeks of combined chemotherapy and
radiation. The concurrent therapy begins about four to
eight weeks after surgery.
Most patients also received continuous-infusion 5-FU
chemotherapy. This is a form of
chemotherapy that enhances the ability of radiation to
damage DNA, the building block of the rapidly
dividing cancer cells. Patients take four weeks off at the
conclusion of their initial therapy and then
may receive maintenance chemotherapy, as prescribed, in the
weeks and months ahead.
Pancreatic cancer strikes about five out of 100,000
people each year in the United States.
Because pancreatic cancer often has no symptoms in its
early stages, cancerous tumors often go
unnoticed until the cancer advances and individuals become
ill. Prognosis is poor for long-term survival,
with only about 5 percent of pancreatic cancer patients
surviving five years after their diagnosis.
The most aggressive and effective form of treatment
for pancreatic cancer is a complicated
surgery commonly known as the Whipple procedure (used in
this study), in which the gallbladder,
common bile duct, part of the duodenum and the head of the
pancreas are generally removed.
Surgeons at The Johns Hopkins Hospital have performed more
than 3,000 Whipple procedures over
the past 25 years.
The study was funded by the Johns Hopkins Department
of Radiation Oncology and Molecular
Michael Swartz, Charles Hsu, Jordan Winter, Timothy
Pawlik, Elizabeth Sugar, Ray Robinson,
Daniel Laheru, Elizabeth Jaffee, Ralph Hruban, Kurtis
Campbell, Christopher Wolfgang, Fariba Asrari,
Ross Donehower, Manuel Hidalgo, Luis Diaz, Charles Yeo,
John Cameron, Richard Schulick and Ross
Abrams, all of Johns Hopkins, assisted with this study.