JOHN YORDY, MD, PHD
ATLANTA—ASTRO 2013 was filled with many interesting and practice-changing results from clinical trials, as well as some provocative and hypothesis-generating non-prospective studies.
Although the dominant theme of the meeting was prostate cancer, every cancer type and treatment technique saw significant advances in our understanding of diagnosis, treatment, and assessment of response. In addition, measurement and assessment of quality of life was emphasized in many presentations as we begin to appreciate the significance of quality of life in addition to therapeutic treatment efficacy in the overall outcomes for our patients.
Whole brain radiation therapy (WBRT) is considered standard of care for patients with unresectable metastatic cancer to the brain. However, data from a meta-analysis was presented to challenge this assumption using individual patients from three randomized clinical trials—one from North America, on from Europe. and one from Asia (Abstract #LBA3). Overall survival was analyzed for patients with one to four brain metastases, comparing use of stereotactic radiosurgery (SRS) alone or combined with WBRT.
Interestingly, a survival advantage was seen for SRS alone in younger patients, with the most pronounced benefit seen in the youngest patients and an overall benefit seen in all patients less than 50 years old, with no increased risk of developing distant brain failure. These findings are significant since WBRT, with the concomitant risk for decrement in short-term memory and other quality-of-life issues, may now be potentially avoided, or at least delayed, for certain patients.
In addition, reducing dose to the hippocampus during WBRT helps to preserve short-term memory for up to six months compared with a historical Phase III trial that administered WBRT without hippocampal sparing (Abstract #LBA1).
RTOG 0933 was a prospective single-arm Phase II trial of 113 patients with measurable brain metastases outside a 5 mm margin around the hippocampus. The dose to the entire hippocampus was at most one third of the dose to the whole brain, with the maximum point dose less than two thirds of the dose to the whole brain.
The primary endpoint for the trial was the Hopkins Verbal Learning Test—Delayed Recall at four months. For the 42 analyzable patients at four months, the average decline was seven percent, compared with the historical control of 30 percent. Six months after treatment, 29 analyzable patients had a two percent decline from baseline, indicating that patients with longer survival may derive an even greater benefit from sparing the hippocampus during WBRT.
Two different dosing schemes for small (≤ 5 cm) peripheral (≤ 2 cm from the tracheo-bronchial tree) node-negative patients—34 Gy in a single fraction or 12 Gy in four fractions delivered on consecutive days—were compared in RTOG 0915 (Abstract #6). The rate of grade 3 toxicities was 10 percent and 13 percent, respectively, similar to the reported 13 percent from the previous RTOG 0236, with no differences in one-year overall survival, recurrence-free survival or primary tumor control (97%) between the two arms.
Because of the equivalency of these two arms, the pre-specified winner was chosen to be the single 34 Gy fraction arm, which is now considered the exploratory arm for future clinical trials.
The appropriate length of total androgen suppression (TAS) was evaluated in RTOG 9910, a randomized Phase III trial of 1,490 patients with intermediate-risk prostate cancer (Abstract #1). Twenty-four months of neoadjuvant (NEO) TAS was compared with four months of NEO TAS followed by eight weeks of radiation therapy with concurrent TAS. There was no difference in overall survival, in non-prostate cancer-related death, and in PSA failure, but there was a significantly higher rate of hot flashes and erectile dysfunction in patients with long-term NEO TAS compared with short-term, leading to the recommendation of four months of NEO TAS for intermediate-risk patients.
Quality of life (QoL) during cancer treatment is now a recognized core component of overall care during and after treatment. Patient-reported QoL data were reported for the prospective RTOG 0617, which compared two different doses of radiation therapy (60 Gy vs. 74 Gy), with concurrent carboplatin/paclitaxel, with or without the addition of cetuximab (Abstract #2).
A planned interim analysis demonstrated decreased overall survival in the high-dose arm, so this arm was closed. Since there were very few differences in provider-reported toxicities between the two arms, analysis of patient-reported QoL was undertaken using the Functional Assessment of Cancer Therapy-Trial Outcome Index, which is a compilation of physical well-being, functional well-being, and lung cancer subscale results.
A clinically meaningful decline was observed at three months post-treatment for the 74 Gy arm compared with the 60 Gy arm, which resolved at 12 months. In addition, intensity-modulated radiation therapy was associated with a lower decline in QoL than the conventional 3D conformal radiation therapy, which was unexpected, demonstrating that advanced radiation techniques may help to further reduce the magnitude of decline in QoL.
All the abstracts noted here can be accessed via this link: http://online.myiwf.com/astro2013/Abstract.aspx