(P 74) SACRAL CHORDOMA: A RANDOMIZED & OBSERVATIONAL STUDY ON SURGERY VS DEFINITIVE RADIOTHERAPY IN PRIMARY LOCALIZED DISEASE (SACRO). INTERIM ANALYSIS

Objective: Surgery with or without high-dose RT are the only curative treatments available for primary and localized sacral chordoma. Prospective studies comparing these two approaches have never been conducted and so far agreement on the optimal treatment strategy for these patients is lacking. The Italian Sarcoma Group (ISG) has promoted an international, prospective randomised/observational clinical trial aimed at identifying the best treatment modality for patients with primary localized sacral chordoma in terms of efficacy, side effects / quality of life (QoL) and long-term morbidities.

Methods: As from March 2017, patients are being enrolled at 16 centers worldwide. The following eligibility criteria are used: >/= 18 years, histologically confirmed diagnosis of chordoma (including positive immunostaining for nuclear brachyury), disease arising from the sacrum (from S1 to coccyx), primary and localized tumor amenable to receive either en-bloc resection with R0 margins surgery or definitive RT. Enrolled patients are asked to choose among 3 alternative options: surgery (+/- RT) (Arm A); definitive RT (Arm B), or randomization to either surgery (+/- RT) or definitive RT (Arm C). Definitive RT treatment can be delivered with three modalities: proton-therapy, mixed photon/proton RT, and carbon-ion RT. Study primary endpoint is relapse-free survival. Overall survival (OS) and QoL are secondary endpoints. This study is designed following a Bayesian statistical approach; the final objective of the statistical analysis will be to estimate a posterior probability distribution of the relative efficacy of the two treatment strategies being compared. The study is currently open to the accrual (ClinicalTrials.gov NCT02986516). The study is currently open to accrual; we report here the results of the second interim analysis (August 2022), while the 3rd interim analysis is ongoing and will be reported at the meeting.

Results: Between March 2017 and March 2023, 136 patients were enrolled in the trial: This exceedes the expected patient accrual, that was 122 (1.7 monthly). None of the patient accepted to be randomized and all patients chose to entered the observational cohorts (Arm A and B). Male patients are more represented in the study (N=94, 69%) and patient median age is 61 years. Median tumor size is 8.4 cm, with 76 (57%) and 60 (43%) tumors located above and below S3, respectively. Seventy-six (56%) and sixty (44%) patients underwent surgery (Arm A) and definitive RT (Arm B), respectively. Among patients treated with surgery, R0 margins were achieved in 81% of surgical resections, while 7% of patients had macroscopically incomplete resection. Among patients treated with definitive RT, 90% received carbon-ions 10% protons. The vast majority of patients (96%) received at least 73.6 Gy. Post-treatment morbidity was consistent with previously series for Arm A and B. At the cut-off date of the second interim analysis (August 2022), 87 patients were evaluable. At a median follow up of 40 months (CI 95% 30-51 months), chordoma recurrences were observed in 4/38 (11%) and 10/49 (20.4%) patients in Arm A and B, respectively, with no statistically significant differences (log-rank test, P=0.757). Consequently, OS did not differ between patients enrolled in Arm A or B (Arm A: 2/38, 5.2%; Arm B: 3/49, 6.1%; log-rank test, P=0.408). The 3rd interim analysis is ongoing and will be reported at the meeting.

Conclusion: Actual accrual rate is above expectations. Interestingly, none of the 136 patients who have entered the study so far accepted to enter the randomized part of the study. According to the Bayesian study design interim analysis are provided yearly, without showing any statistically significant difference in recurrence and survival rate between wide en-bloc surgical resection or definitive RT. Therefore the study is continuing its recruitment and QoL date collection is ongoing.