Radiation Plus Procarbazine, CCNU, and Vincristine in Low-Grade Glioma.
N Engl J Med 374:1344-55
The publication of long-term follow-up for patients treated on Radiation
Therapy Oncology Group (RTOG) trial 9802 in the April 7 edition of the
New England Journal of Medicine was significant to me for a number of
reasons. I was involved because completion of a large randomized trial
for a relatively uncommon tumor required collaboration between multiple
national cooperative groups for clinical cancer research. In the late
1990s, when this trial was designed, I was the Brain Tumor Committee Chair
for the Southwest Oncology Group (SWOG), one of those cooperative groups
that came along side of the RTOG in order to accrue enough patients to
achieve meaningful results.
The trial attempted to determine if addition of chemotherapy to radiation
could improve survival compared to radiation therapy alone for patients
with low-grade gliomas, a type of tumor that originates from cells in
the brain. The trial was directed toward patients with tumors in this
category that were of higher risk either because of patient age (over
40 years) or less than complete removal of grossly visible tumor by the
neurosurgeon, and used a 3 drug chemotherapy regimen (PCV) that was popular
at the time the trial was designed. Results were previously published
showing improved disease-free survival (that is, survival without evidence
of the tumor coming back) among the patients who randomly received PCV
in addition to radiation. This latest publication in the New England Journal
of Medicine (NEJM) was important because after long-term follow-up (an
average of almost 12 years) there was an improvement in overall survival
for the patients getting chemotherapy plus radiation, with 60% of patients
alive at 10 years compared to 40% treated with radiation alone (after
surgery or biopsy).
The “journey” of this study illustrate some of the difficulties
with cancer research, particularly with tumor types that are less common
and have average survival of several years. It can take a long time to
enroll enough patients on such a trial to be able to detect statistically
meaningful results, and it can take a long time for those meaningful results
to become apparent. As a result, newer agents can come along and practice
patterns can change, leaving doctors who treat patients with these tumors
with questions. For example, PCV is rarely used anymore. In high-grade
gliomas, an oral chemotherapy drug called temozolomide has been found
to improve survival, is easier to deliver than PCV, and is well-tolerated
by patients. Should patients with low-grade gliomas receive PCV or temozolomide?
Nobody knows that answer for certain, but my guess is that most patients
will receive temozolomide.
From my personal and vocational perspective, this article had great meaning.
The first phase of my career was spent in academic medicine at the University
of Washington while the last 16 years has been spent practicing in the
rural setting of Celilo Cancer Center at MCMC. Although there are tremendous
differences in those practice settings, I have had continued academic
opportunities that link those two phases of my career through my past
relationships with SWOG and the University of Washington. I’ve co-authored
15 scientific publications since leaving UW, an “extra” activity
to my clinical practice at Celilo that has sustained intellectual interest
and relationships with colleagues. This particular paper’s importance
to me is that it represents something with potential far-reaching impact
in care of patients, something that tends to be a fairly rare event over
an individual’s career studying cancer therapies. The importance
is also reflected in NEJM’s publication of the trial results, as
it is the most cited medical journal. I’m grateful to co-investigators
like Drs. Shaw and Buckner for championing the vision and completion of
this trial, and their inclusion of me in the process.
Written by Dr. Keith Stelzer, MD, PhD