IMPORTANCE Malignant spinal canal compression, a major complication of metastatic cancer, is managed with radiotherapy to maintain mobility and relieve pain, although there is no standard radiotherapy regimen. OBJECTIVE To evaluate whether single-fraction radiotherapy is noninferior to 5 fractions of radiotherapy. DESIGN, SETTING, AND PARTICIPANTS Multicenter noninferiority randomized clinical trial conducted in 42 UK and 5 Australian radiotherapy centers. Eligible patients (n = 686) had metastatic cancer with spinal cord or cauda equina compression, life expectancy greater than 8 weeks, and no previous radiotherapy to the same area. Patients were recruited between February 2008 and April 2016, with final follow-up in September 2017. INTERVENTIONS Patients were randomized to receive external beam single-fraction 8-Gy radiotherapy (n = 345) or 20 Gy of radiotherapy in 5 fractions over 5 consecutive days (n = 341). MAIN OUTCOMES AND MEASURES The primary end point was ambulatory status at week 8, based on a 4-point scale and classified as grade 1 (ambulatory without the use of aids and grade 5 of 5 muscle power) or grade 2 (ambulatory using aids or grade 4 of 5 muscle power). The noninferiority margin for the difference in ambulatory status was −11%. Secondary end points included ambulatory status at weeks 1, 4, and 12 and overall survival. RESULTS Among 686 randomized patients (median [interquartile range] age, 70 [64-77] years; 503 (73%) men; 44% had prostate cancer, 19% had lung cancer, and 12% had breast cancer), 342 (49.8%) were analyzed for the primary end point (255 patients died before the 8-week assessment). Ambulatory status grade 1 or 2 at week 8 was achieved by 115 of 166 (69.3%) patients in the single-fraction group vs 128 of 176 (72.7%) in the multifraction group (difference, −3.5% [1-sided 95% CI, −11.5% to ϱ]; P value for noninferiority = .06). The difference in ambulatory status grade 1 or 2 in the single-fraction vs multifraction group was −0.4% (63.9% vs 64.3%; [1-sided 95% CI, −6.9 to ϱ]; P value for noninferiority = .004) at week 1, −0.7% (66.8% vs 67.6%; [1-sided 95% CI, −8.1 to ϱ]; P value for noninferiority = .01) at week 4, and 4.1% (71.8% vs 67.7%; [1-sided 95% CI, −4.6 to ϱ]; P value for noninferiority = .002) at week 12. Overall survival rates at 12 weeks were 50% in the single-fraction group vs 55% in the multifraction group (stratified hazard ratio, 1.02 [95% CI, 0.74-1.41]). Of the 11 other secondary end points that were analyzed, the between-group differences were not statistically significant or did not meet noninferiority criterion. CONCLUSIONS AND RELEVANCE Among patients with malignant metastatic solid tumors and spinal canal compression, a single radiotherapy dose, compared with a multifraction dose delivered over 5 days, did not meet the criterion for noninferiority for the primary outcome (ambulatory at 8 weeks). However, the extent to which the lower bound of the CI overlapped with the noninferiority margin should be considered when interpreting the clinical importance of this...

LBA10004 Background: SCC is a common complication of metastatic cancer. Most pts receive RT to improve neurological function and mobility and to relieve pain. There is no standard schedule (RT ranges from single dose 8Gy to 40Gy in 20 fractions). SCORAD III was conducted to show whether a single fraction is as effective as multifraction RT without compromising patient outcomes. Methods: Pts from 43 UK and 4 Australian sites were randomized (1:1) to receive external beam spinal canal RT as a single dose of 8Gy or 20Gy in 5 fractions; stratified by RT center, ambulatory status (AS), site of primary, and presence or absence of nonskeletal metastases. Eligible pts had spinal cord or cauda equina (C1-S2) compression confirmed by MRI/CT scan, treatable within a single radiation field, life expectancy >8 weeks (wks), no previous RT to the same area. Primary endpoint was AS at wk 8: graded 1 (full function) to 4 (no/flicker motor power). The noninferiority margin was 11% for comparing the proportion of patients with AS 1 or 2 at wk 8 (whether maintained from baseline or improved from AS 3-4). Results: 688 pts were randomized Feb 2008 to Apr 2016 (n=345 single dose, n=343 multifraction). 73% were male; median age 70 years; ambulatory with/without walking aids 66%; 44% prostate, 18% lung, 11% breast, 11% gastrointestinal. Baseline characteristics were balanced. 69.5% (114/164 pts evaluable at wk 8) single dose vs. 73.3% (129/176) multifraction had AS 1-2 at wk 8 (risk difference: -3.78%, 90%CI -11.85 to 4.28). Importantly, overall survival (OS) was very similar: median OS 12.4 wks single dose vs. 13.7 multifraction, (hazard ratio 1.02 [95%CI 0.86-1.21], p=0.81). Proportion of pts with adverse events was similar for grade 3-4 (20.6% single dose vs. 20.4% multifraction), but grade 1-2 events were lower with single dose (51.0% vs. 56.9%). Conclusions: Using a single dose of 8Gy in pts with metastatic SCC was as effective as multiple fractions for AS at 8 wks and OS. We now recommend using single dose RT in this setting, with the major benefit of requiring only a single instead of multiple hospital visits, important when considering the short survival in these pts. Clinical trial information: 97108008.

BackgroundProstate cancer is the most common cancer in males in the UK and affects around 105 men for every 100,000. The role of radiotherapy in the management of prostate cancer significantly changed over the last few decades with developments in brachytherapy, external beam radiotherapy (EBRT), intensity-modulated radiotherapy (IMRT), and image-guided radiotherapy (IGRT). One of the challenging factors of radiotherapy treatment of localized prostate cancer is the development of acute and late genitourinary and gastrointestinal toxicities. The recent European guidelines suggest that there is no consensus regarding the timing of high-dose rate (HDR) brachytherapy and EBRT. The schedules vary in different institutions where an HDR boost can be given either before or after EBRT. Few centers deliver HDR in between the fractions of EBRT.ObjectiveAssessment of acute genitourinary and gastrointestinal toxicities at various time points to better understand if the order in which treatment modality is delivered (ie, HDR brachytherapy or EBRT first) has an effect on the toxicity profile.MethodsTiming of HDR brachytherapy with EBRT in Prostate CAncer (THEPCA) is a single-center, open, randomized controlled feasibility trial in patients with intermediate and high-risk localized prostate cancer. A group of 50 patients aged 18 years old and over with histological diagnosis of prostate cancer (stages T1b-T3BNOMO), will be randomized to one of two treatment arms (ratio 1:1), following explanation of the study and informed consent. Patients in both arms of the study will be treated with HDR brachytherapy and EBRT, however, the order in which they receive the treatments will vary. In Arm A, patients will receive HDR brachytherapy before EBRT. In Arm B (control arm), patients will receive EBRT before HDR brachytherapy. Study outcomes will look at prospective assessment of genitourinary and gastrointestinal toxicities. The primary endpoint will be grade 3 genitourinary toxicity and the secondary endpoints will be all other grades of genitourinary toxicities (grades 1 and 2), gastrointestinal toxicities (grades 1 to 4), prostate-specific antigen (PSA) recurrence-free survival, overall survival, and quality of life.ResultsResults from this feasibility trial will be available in mid-2016.ConclusionsIf the results from this feasibility trial show evidence that the sequence of treatment modality does affect the patients’ toxicity profiles, then funding would be sought to conduct a large, multicenter, randomized controlled trial.Trial RegistrationInternational Standard Randomized Controlled Trial Number (ISRCTN): 15835424; http://www.isrctn.com/ISRCTN15835424 (Archived by WebCite at http://www.webcitation.org/6Xz7jfg1u).

LBA10004 The full, final text of this abstract will be available at abstracts.asco.org at 2:00 PM (EDT) on Friday, June 2, 2017, and in the Annual Meeting Proceedings online supplement to the June 20, 2017, issue of the Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Saturday edition of ASCO Daily News.

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