The four studies assessed quality of life (QOL) and toxicities following treatment for proton therapy. All reported similar excellent outcomes as studies previously published in peer-review journals, and several add to a growing body of data that represent patient-reported outcomes.
Study presenters included radiation oncologists from MD Anderson Cancer Center at the University of Texas, the University of Florida Proton Therapy Institute, and ProCure Proton Therapy Center in Oklahoma City.
MD Anderson research
In the first study, presented by Dr. Andrew K. Lee, associate professor of radiation oncology, 1,090 men were treated at MD Anderson's proton center, Scripps Proton Therapy Center, Loma Linda Medical Center, Massachusetts General Hospital, or the University of Florida Proton Therapy Institute.
The patients completed an Expanded Prostate Cancer Index Composite (EPIC) survey at least one year and again up to 10 years following proton therapy treatment. They also may have received hormone therapy.
The cohort of prostate cancer patients was compared to a cohort of 112 healthy men. The EPIC survey, which is designed to assess a patient's health-related quality of life, uses a scoring system of 1 (poor) to 100 (perfect). The median age of the healthy patient group was 64.8 years, compared with 65 years for those with prostate cancer.
The prostate cancer patients scored 89.8 for urinary quality and 92.7 for bowel functions, compared with scores of 89.5 and 92.4, respectively, for healthy men.
QOL scores for sexual function were not comparable, with prostate cancer patients scoring lower. The differences in sexual function scores were driven by men who were older at the time of treatment, who were on hormone therapy, and who had higher Gleason scores, according to Lee.
"The strengths of this study are that it involved a large number of patients from multiple institutions and, for more than half of the respondents, represented outcomes reported four or more years following treatment," Lee said. "It reconfirms the findings of other studies and is consistent with our institution's prospective studies."
Lee also discussed findings of a study of 299 prostate cancer patients with a median age of 65 years. Between 2006 and 2009, these patients underwent proton therapy at MD Anderson Cancer Center, with or without hormone therapy. One cohort received 75.6 Gray equivalents (GyE) at 1.8-GyE fractions, while the other cohort received 76 GyE at 2-GyE fractions.
All participants completed an EPIC survey before receiving treatment and at periodic intervals following their therapy. The researchers found a small but statistically significant difference in the groups in urinary and bowel function from their baseline scores to their scores at three years after treatment. However, these changes were not clinically significant. There was no meaningful difference in QOL changes between the two groups except for sexual function.
The researchers also assessed toxicities experienced by the patients. The three-year, cumulative rates of grade 2 urinary side effects were 24.1% for the group that received the lower fraction, and 17.6% for those who received the higher fraction. Both groups reported high satisfaction rates with their treatment, at 91% and 93.5%, respectively.
Proton therapy in the community
Historically, proton therapy has been delivered by large academic centers, but a private radiation oncology practice in Oklahoma City was the first to offer this treatment in a community setting for prostate cancer patients. From its first day of operation, the center established a patient database and opened a registry study.
Radiation oncologist Dr. Sameer Keole said that he and his colleagues prospectively analyzed toxicities and a group of 76 prostate cancer patients completed EPIC surveys. The patients ranged in age from 43 to 84, with a median age of 65. Forty-six percent had stage I low-risk disease, 37% had stage IIA intermediate-risk disease, and the remainder had stage IIB high-risk disease. The patients completed an EPIC survey prior to treatment and at three, six, 12, 18, and 24 months following treatment.
"Survey findings showed that urinary and bowel QOL satisfaction scores were identical out to 18 months following treatment," Keole said. "Genitourinary and gastrointestinal function appeared to be stable in patients starting as early as three months post-treatment. There appeared to be a slight decline in sexual score in men who did not receive androgen deprivation therapy."
Minimizing rectal toxicity
Dr. Nancy Mendenhall, medical director of the University of Florida Proton Therapy Institute, reported the findings of a prospective study assessing the usefulness of dose-volume constraints to minimize the risk of rectal toxicity. In the study, early- and intermediate-risk prostate cancer patients received image-guided proton therapy.
The outcomes of 171 men were followed for a minimum of five years. They had received doses from 78 to 82 cobalt gray equivalents (CGE) delivered in 2-CGE fractions over eight weeks. Toxicity rates were scored and disease was assessed.
"Biochemical progression was 99% at three and five years following treatment," according to Mendenhall. "There were only two patients who developed grade 3+ gastrointestinal toxicities. Both patients were on anticoagulation and both incidents did not recur following successful treatment."
She also said that the majority of grade 2 or worse toxicities -- about 7% of the total -- consisted of rectal bleeding and/or proctitis.
"What we wanted to do in this study was try to correlate gastrointestinal toxicities with dose distribution," Mendenhall said. "What we were able to show was a significant correlation with the volume of rectum that received various dose levels. The dose levels were as low as 30 CGE up to 75 CGE. We wanted to see if there was a relationship between toxicity and volume of rectum receiving certain doses. There was; it was quite striking."
The other study objectives were to provide dose-constraint guidelines for other proton therapy centers to help them achieve optimal results, and to provide some parameters for designing future comparative trials. The results were comparable to those of previously published studies.
"The value of these and other studies about prostate cancer patients who received proton therapy treatment confirms what we already knew about excellent outcomes for these patients," Mendenhall said. "They show that this treatment produces as high a therapeutic ratio for early- and intermediate-risk prostate cancer patients as any other type of treatment available."