Prospective, randomized dose-escalation trial with proton-based radiation for skull base and cervical spine chondrosarcomas: 30-year outcomes from PROG 85-26
Abstract Background To determine if dose escalation improves outcomes for chondrosarcomas (CHS) of the base of the skull (BOS) and the cervical spine (CS). Methods A prospective, randomized, dose-escalation trial was designed for patients with CHS of the BOS and CS. Patients were randomly assigned to 70 Gy (RBE) or 76 Gy (RBE). The primary endpoint was local failure (LF). Secondary endpoints included overall survival (OS), cancer-specific survival (CSS), progression-free survival (PFS), and treatment-related toxicities. Results Between 1987 and 2007, 105 patients were randomized, median follow-up was 29.2 years (IQR, 26.7-32.4). Forty-six patients were assigned to 70 Gy (RBE) and 59 were assigned to 76 Gy (RBE). LF at 5-, 10-, and 20 years were 7%, 9%, and 11% for 70 Gy (RBE), and 10%, 15%, and 19% for 76 Gy (RBE) (P = .16). Like LF rates, there was no benefit in dose escalation for OS (P = .28) and CSS (P = .22). Progression-free survival at 5-, 10-, and 20 years was 93%, 89%, and 77% for the low-dose group and 83%, 71%, and 59% for the high-dose group (P = .069). Late RT injury ≥ grade 3 was reported in a total of 19 (18%) patients across both dose levels, with 11% in the low-dose group and 24% in the high-dose group (P = .13). Conclusions This is the first and largest trial of patients with grade I/II BOS and CS CHS evaluating dose escalation for tumor control. Proton-based RT is effective and safe for these tumors, but there is no apparent benefit in dose escalation. Clinical Trial Information NCT00592748.
Liver Metastasis–Directed Ablative Radiotherapy in Pancreatic Cancer Offers Prolonged Time Off Systemic Therapy in Selected Patients
Objectives We evaluated the outcomes of metastatic pancreatic cancer (MPC) patients who underwent liver metastases (LMs)–directed ablative radiotherapy (RT) and sought to characterize patients with more favorable prognosis. Methods A retrospective analysis of 76 MPC patients who underwent ablative RT (median dose, 50 Gy) to LM at 3 academic centers between 2008 and 2018 was performed. Endpoints were local control (LC), progression-free survival, and overall survival (OS) since RT. Results Median follow-up was 10.9 months. Liver metastases were metachronous in 68%. Before RT, LM was responsive/stable on chemotherapy (CTX) in 36% whereas progressive in 43%. Median carbohydrate antigen 19-9 (CA 19-9) at RT was 334 U/mL. After RT, 32% had ≥6 months of CTX break. Twelve-month outcomes were: LC, 66%; progression-free survival, 7%; and OS, 38%. On multivariable analysis, Eastern Cooperative Oncology Group 2–3 (hazard ratio [HR], 13.49; P < 0.01), progressive LM on CTX (HR, 3.26; P < 0.01), and higher CA 19-9 (log 10 scale; HR, 1.39; P < 0.01) at RT predicted worse OS. Conclusions Ablative RT to LM in setting of MPC may offer LC of systemic disease and thus quality time off CTX. Selected patients with good performance status, stable/responsive LM on CTX, and lower CA 19-9 have more favorable prognosis.