Radiosurgery Compared To External Beam Radiotherapy for Localized Spine Metastasis: Phase III Results of NRG Oncology/RTOG 0631

Abstract

Materials/Methods: Women with HREC (FIGO-stage I grade 3 with deep myometrial invasion and/or LVSI; stage II or III; or serous/ clear cell histology) were randomized (1:1) to CTRT (two cycles of cisplatin 50 mg/ m 2 in week 1&4 of RT, followed by four cycles of carboplatin AUC5 and paclitaxel 175 mg/m 2 at 3-week intervals) or RT alone (48.6 Gy in 1.8 Gy fractions). The co-primary endpoints were overall survival (OS) and failure-free survival (FFS). Secondary endpoints vaginal, pelvic, and distant recurrence were analyzed according to first site of recurrence. The Kaplan-Meier method, log-rank test, and Cox regression analysis were used according to intention-to-treat, and competing risk methods for FFS and recurrence. Analysis of the primary endpoints was adjusted for the stratification factors (participating group, lymphadenectomy, stage of cancer and histological type). PORTEC-3 is registered with ISRCTN (ISRCTN14387080) and ClinicalTrials.gov (NCT00411138). Results: Six hundred eighty-six women were enrolled between 2006 and 2013; 26 were excluded for immediate informed consent withdrawal or ineligibility, leaving 660 patients in the final analysis, 330 CTRT and 330 RT. Median follow-up was 72.6 months (IQR 59.9-85.6). 5-year OS was 81.4% vs 76.1% for CTRT vs RT [HR 0.70, 95% CI 0.51-0.97, pZ0.034], and 5-year FFS was 76.5% vs 69.1% [HR 0.70, 95% CI 0.52-0.94, pZ0.016]. Women with serous cancers had significantly lower OS compared with other histologies (62.0% vs 81.9% at 5 years), while 5-year OS for serous cancer was 71.4% with CTRT vs 52.8% with RT [HR 0.48, 95% CI 0.24-0.96, pZ0.037], and 5-year FFS was 59.7% vs 47.9% [HR 0.42, 95% CI 0.22-0.80, pZ0.008]. For women with stage III disease an absolute 5-year OS improvement of 10% (HR 0.63, 95% CI 0.41-0.99, pZ0.043) and FFS improvement of 12.5% at (HR 0.61 (95% CI 0.42-0.89, pZ0.011) was found with CTRT. Distant metastases were the first site of recurrence in the majority of patients, 21.4% (CTRT) vs 29.1% (RT) (pZ0.047), and most patients received chemotherapy for recurrence. Survival after recurrence was 1.2 vs 1.4 years (pZ0.7). Pelvic control was high in both arms with isolated vaginal or pelvic recurrence in only 1.2%. Conclusion: This updated analysis with median FU of 6 years showed a significantly improved OS and FFS with combined adjuvant chemotherapy and radiation therapy for HREC. The largest improvement was found for women with stage III and/or serous cancers. Shared decision making remains essential to weigh the costs and benefits for individual patients.

Imaging response assessment following stereotactic body radiotherapy for solid tumour metastases of the spine: Current challenges and future directions

“…However, a more recent study found that for the palliation of vertebral metastases, SBRT is only cost‐effective if the patient has a good prognosis of at least 11 months 103 . Importantly, this finding was based on the phase III RTOG 0631 study 12 hypothesising that SBRT would result in an improvement in pain of 20% compared to EBRT – this endpoint was subsequently reported negative and so we must question the validity of the cost‐effectiveness study’s findings. While helpful, these analyses remain somewhat limited as they do not take into account all of the downstream effects of spine SBRT compared to EBRT including the increased risk of vertebral fracture which may require intervention and the requirement for longitudinal imaging surveillance per SPINO recommendations.…”

“…With spine SBRT, local control rates are reported as being as high as 80–90% at 1–2 years with minimal rates of treatment‐related myelopathy 7‐11 . RTOG 0631, a phase III randomised trial comparing palliative EBRT (8Gy/1#) to spine SBRT (16‐18Gy/1#), recently reported at ASTRO 2019 that there was no difference in pain control at up to 6 months between the two arms 12 . However, important long‐term outcomes including local control, retreatment rates and vertebral compression fracture (VCF) rates are awaited and should be considered before conclusions from the study can be drawn.…”

Patient-Reported Outcomes of Oligometastatic Patients After Conventional or Stereotactic Radiation Therapy to Bone Metastases: An Analysis of the PRESENT Cohort

“…Our results are in line with a recently presented phase 3 trial in patients with limited spinal metastatic disease. 15 In this trial, pain response was defined as a 3-point improvement on the NRS with no increase in pain medication. No difference in pain response or QoL was found between SBRT (16-18 Gy) and 3DCRT (8 Gy) at 3 months (40% vs 58%) in 339 eligible patients.…”

“…No improvement of QoL was reported after SBRT compared with 3DCRT. [12][13][14][15] The subgroup of patients with oligometastatic bone disease might especially benefit from more effective and long-term palliation with SBRT. Furthermore, radically treating oligometastatic disease can theoretically improve systemic disease control, which has recently been shown in a phase 2 RCT.…”

The Role of Radiotherapy in the Management of Bone Metastasis

“…Sadece tutulum yeri hedef alınır, böylelikle nöral yapılar yüksek dozdan korunmuş olur (Figür 1). Bununla birlikte, palyasyon gerektiren durumda tek doz konvansiyonel RT (8 Gy) ile tek doz SBRT'nin (16/18 Gy) karşılaştırıldığı faz3 randomize çalışmada ağrı kontrolünün konvansiyonel kolda daha iyi olduğu gözlenmiştir (17).…”