Celilo Radiation Oncologist, Dr. Keith Stelzer Published in New England Journal of Medicine

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