Palmerini Emanuela, Pazzaglia Laura, Cevolani Luca, Pratelli Loredana, Pierini Michela, Quattrini Irene, Carretta Elisa, Manara Maria Cristina, Pasello Michela, Frega Giorgio, Paioli Anna, Longhi Alessandra, Cesari Marilena, Hakim Rossella, Ibrahim Toni, Campanacci Laura, Staals Eric Lodewijk, Donati Davide Maria, Benassi Maria Serena, Scotlandi Katia, Ferrari Stefano
Osteoncology, Bone and Soft Tissue Sarcoma and Innovative Therapy, IRCCS Istituto Ortopedico Rizzoli, Via Pupilli 1, 40136 Bologna, Italy.
SSD Laboratory of Experimental Oncology, IRCCS Istituto Ortopedico Rizzoli, Via di Barbiano 1/10, 40136 Bologna, Italy.
Cancers (Basel). 2022 Jun 10;14(12):2863. doi: 10.3390/cancers14122863.
Background: Giant cell tumors of bone (GCTB) are osteolytic tumors. Denosumab, a RANK-L inhibitor, is approved for GCTB. Data on serum bone turnover marker (sBTM) changes are lacking. We present a phase II correlative study on sBTMs in GCTB patients treated with denosumab. Methods: All GCTB patients receiving denosumab within a multicentre, open-label, phase 2 study were enrolled. Serum levels of carboxyterminal-crosslinked-telopeptide of type I collagen (s-CTX), alkaline phosphatase (ALP), bone-alkaline phosphatase (bALP), parathyroid hormone (sPTH), and osteocalcin (OCN) were prospectively assessed (baseline, T0, 3 months, T1, 6 months, T2). The primary endpoint was assessment of sBTM changes after denosumab; the secondary endpoints were disease-free survival (DFS) and sBTM correlation. Results: In 54 cases, sBTMs decreased during denosumab treatment except for sPTH. With a median follow-up of 59 months, 3-year DFS was 65% (%CI 52−79), with a significantly worse outcome for patients with high (≥500 UI/mL) s-CTX at baseline, as compared to low s-CTX (<500 UI/mL) (3-year DFS for high CTX 45% (95%CI 23−67) vs. 75% (95%CI 59−91) for low s-CTX. Higher median ALP and s-CTX were found for patients with tumor size ≥ 5 cm (p = 0.0512; p = 0.0589). Conclusion: Denosumab induces ALP/OCN and s-CTX reduction. High baseline s-CTX identifies a group of patients at higher risk of progression of the disease.
骨巨细胞瘤（GCTB）是溶骨性肿瘤。地诺单抗，一种RANK-L抑制剂，已被批准用于治疗GCTB。目前缺乏血清骨转换标志物（sBTM）变化的数据。我们开展了一项关于接受地诺单抗治疗的GCTB患者sBTM的II期相关性研究。方法：纳入多中心、开放标签II期研究中所有接受地诺单抗治疗的GCTB患者。前瞻性评估血清I型胶原羧基末端交联肽（s-CTX）、碱性磷酸酶（ALP）、骨碱性磷酸酶（bALP）、甲状旁腺激素（sPTH）和骨钙素（OCN）水平（基线、T0、3个月、T1、6个月、T2）。主要终点是评估地诺单抗治疗后sBTM的变化；次要终点是无病生存期（DFS）和sBTM相关性。结果：54例患者中，除sPTH外，地诺单抗治疗期间sBTM均下降。中位随访59个月，3年DFS为65%（%CI 52−79），基线时s-CTX高（≥500 UI/mL）的患者结局明显较差，与低s-CTX（<500 UI/mL）患者相比（高CTX患者3年DFS为45%（95%CI 23−67），低s-CTX患者为75%（95%CI 59−91））。肿瘤大小≥5 cm的患者中位ALP和s-CTX更高（p = 0.0512；p = 0.0589）。结论：地诺单抗可降低ALP/OCN和s-CTX。高基线s-CTX可识别出一组疾病进展风险较高的患者。
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