Washington, DC—Patient-reported outcomes (PROs) are increasingly being incorporated into clinical trial design, which has led to advances that benefit patients. Findings from PROs are influencing practice guidelines and changing practice.
At the 2017 annual meeting of the Multinational Association of Supportive Care in Cancer, Deborah Watkins-Bruner, RN, PhD, FAAN, Professor and Robert W. Woodruff Chair in Nursing, Associate Director, Mentorship, Education, and Training, Winship Cancer Institute, Emory University, Atlanta, GA, discussed 2 examples of the influence of PROs on practice changes in radiation oncology.
Radiation Therapy Oncology Group 97-14 Clinical Trial
Although a single fraction of radiation for the treatment of painful bone metastases is standard practice in Europe, US radiologists did not change practice based on European trials showing equivalent outcomes with a single fraction versus 30 fractions for painful bone metastases.
“Painful bone metastases from breast or prostate cancers can be relieved by a single fraction. Radiologists in the United States get paid by fraction, so why would they want to use fewer fractions?” Dr Watkins-Bruner asked, suggesting that the motive is at least partly based on financial gain. Another stated reason for US radiologists not adopting single-fraction treatment was concern about health-related quality of life, which was not assessed in the European clinical trials.
Dr Watkins-Bruner and her colleagues designed the Radiation Therapy Oncology Group 97-14 bone metastases clinical trial to include PROs by using the Brief Pain Inventory (BPI) to assess pain relief and the Functional Assessment of Cancer Therapy - General (FACT-G) questionnaire to assess health-related quality of life (Konski A, et al. Am J Clin Oncol. 2009;32:423-428).
To be eligible for initial randomization to a single fraction of 8 Gy versus 30 Gy, patients had to have a worst pain score of ≥5 on the 10-point BPI scale. The primary outcome was change on the BPI.
Of 907 patients randomized to receive 8 Gy in 1 fraction or up to 30 Gy in 10 fractions, 380 (42%) patients completed the BPI at baseline and at 3 months and 315 (39%) completed the FACT-G at baseline and at 3 months.
Results for pain relief and health-related quality-of-life assessments were equivalent in both arms. At 3 months, on the BPI, complete and partial response rates for 8 Gy were 15% and 50%, respectively, versus 18% and 48% for 30 Gy, respectively. Grade 2 to 4 toxicity was significantly higher with 30 Gy versus 8 Gy (17% vs 10%, respectively; P <.0001), and the rate of retreatment was higher in the 8-Gy arm than the 30-Gy arm (18% vs 9%, respectively; P = .0004).
“In these days of overtreatment, we found that 8 Gy was cost-effective with fewer side effects. We have a clear winner here. This finding went into multiple guidelines. ASTRO [American Society for Radiation Oncology] also changed their guidelines to include a single fraction of 8 Gy as an option, but they are hedging their bets, because they also allow 20 Gy in 5 fractions and 30 Gy in 10 for no good reason. The evidence is clear....30 Gy causes more symptoms. 8 Gy is the general standard worldwide,” Dr Watkins-Bruner told attendees.
NRG Oncology/Radiation Therapy Oncology Group 0415 Clinical Trial
The second study was a phase 3 noninferiority clinical trial comparing conventional fractionation (73 Gy in 41 fractions of 1.5 Gy over 8.2 weeks) with hypofractionation (70 Gy in 8 fractions of 2.5 Gy over 5.6 weeks) in patients with low-risk prostate cancer. No androgen deprivation therapy was allowed.
The noninferiority design was for disease-free survival and overall survival.
“This study of more than 1000 patients showed that hypofractionation was indeed noninferior for disease-free survival. It was a successful trial,” Dr Watkins-Bruner stated.
“Clinician-reported adverse events showed a significant difference in gastrointestinal toxicities, and a slight difference in grade 2 genitourinary effects favoring conventional radiation therapy. We went on to use the EPIC [Expanded Prostate Cancer Index Composite] instrument to determine PROs in patients enrolled in the trial to help interpret results and morbidity,” she noted.
On the EPIC Bowel Domain, at 12 months a slight 1.8 difference was observed on a 100-point scale. No other EPIC domain was significantly different between the 2 treatment arms.
“We don’t think these differences are clinically significant. It may mean 1 more bout of diarrhea with hypofractionation. Patients cannot tell the difference,” Dr Watkins-Bruner added.
Currently, hypofractionation is being considered for inclusion in prostate cancer guidelines as a standard treatment option for the primary treatment of low-risk disease.