Johns Hopkins School of Medicine, Baltimore, MD, USA.
Department of Orthopaedic Surgery, Johns Hopkins University, Baltimore, MD, USA.
Clin Orthop Relat Res. 2022 May 1;480(5):932-945. doi: 10.1097/CORR.0000000000002104. Epub 2021 Dec 28.
Pathologic fracture of the long bones is a common complication of bone metastases. Intramedullary nail stabilization can be used prophylactically (for impending fractures) or therapeutically (for completed fractures) to preserve mobility and quality of life. However, local disease progression may occur after such treatment, and there is concern that surgical instrumentation and the intramedullary nail itself may seed tumor cells along the intramedullary tract, ultimately leading to loss of structural integrity of the construct. Identifying factors associated with local disease progression after intramedullary nail stabilization would help surgeons predict which patients may benefit from alternative surgical strategies.
QUESTIONS/PURPOSES: (1) Among patients who underwent intramedullary nail stabilization for impending or completed pathologic fractures of the long bones, what is the risk of local progression, including progression of the existing lesion and development of a new lesion around the nail? (2) Among patients who experience local progression, what proportion undergo reoperation? (3) What patient characteristics and treatment factors are associated with postoperative local progression? (4) What is the difference in survival rates between patients who experienced local progression and those with stable local disease?
Between January 2013 and December 2019, 177 patients at our institution were treated with an intramedullary nail for an impending or completed pathologic fracture. We excluded patients who did not have a pathologic diagnosis of metastasis before fixation, who were younger than 18 years of age, who presented with a primary soft tissue mass that eroded into bone, and who experienced nonunion from radiation osteitis or an avulsion fracture rather than from metastasis. Overall, 122 patients met the criteria for our study. Three fellowship-trained orthopaedic oncology surgeons involved in the care of these patients treated an impending or pathologic fracture with an intramedullary nail when a long bone lesion either fractured or was deemed to be of at least 35% risk of fracture within 3 months, and in patients with an anticipated duration of overall survival of at least 6 weeks (fractured) or 3 months (impending) to yield palliative benefit during their lifetime. The most common primary malignancy was multiple myeloma (25% [31 of 122]), followed by lung carcinoma (16% [20 of 122]), breast carcinoma (15% [18 of 122]), and renal cell carcinoma (12% [15 of 122]). The most commonly involved bone was the femur (68% [83 of 122]), followed by the humerus (27% [33 of 122]) and the tibia (5% [6 of 122]). A competing risk analysis was used to determine the risk of progression in our patients at 1 month, 3 months, 6 months, and 12 months after surgery. A proportion of patients who ultimately underwent reoperation due to progression was calculated. A univariate analysis was performed to determine whether lesion progression was associated with various factors, including the age and sex of the patient, use of adjuvant therapies (radiation therapy at the site of the lesion, systemic therapy, and antiresorptive therapy), histologic tumor type, location of the lesion, and fracture type (impending or complete). Patient survival was assessed with a Kaplan-Meier curve. A p value < 0.05 was considered significant.
The cumulative incidence of local tumor progression (with death as a competing risk) at 1 month, 3 months, 6 months, and 12 months after surgery was 1.9% (95% confidence interval 0.3% to 6.1%), 2.9% (95% CI 0.8% to 7.5%), 3.9% (95% CI 1.3% to 8.9%), and 4.9% (95% CI 1.8% to 10.3%), respectively. Of 122 patients, 6% (7) had disease progression around the intramedullary nail and 0.8% (1) had new lesions at the end of the intramedullary nail. Two percent (3 of 122) of patients ultimately underwent reoperation because of local progression. The only factors associated with progression were a primary tumor of renal cell carcinoma (odds ratio 5.1 [95% CI 0.69 to 29]; p = 0.03) and patient age (difference in mean age 7.7 years [95% CI 1.2 to 14]; p = 0.02). We found no associations between local disease progression and the presence of visceral metastases, other skeletal metastases, radiation therapy, systemic therapy, use of bisphosphonate or receptor activator of nuclear factor kappa-B ligand inhibitor, type of fracture, or the direction of nail insertion. There was no difference in survivorship curves between those with disease progression and those with stable local disease (= 0.36; p = 0.54).
Our analysis suggests that for this population of patients with metastatic bone disease who have a fracture or impeding fracture and an anticipated survival of at least 6 weeks (completed fracture) or 3 months (impending fracture), the risk of experiencing local progression of tumor growth and reoperations after intramedullary nail stabilization seems to be low. Lesion progression was not associated with the duration of survival, although this conclusion is limited by the small number of patients in the current study and the competing risks of survival and local progression. Based on our data, patients who present with renal cell carcinoma should be cautioned against undergoing intramedullary nailing because of the risk of postoperative lesion progression.
Level III, therapeutic study.
长骨病理性骨折是骨转移的常见并发症。髓内钉稳定可以预防性使用（用于即将发生的骨折）或治疗性使用（用于已发生的骨折），以保持移动性和生活质量。然而，在这种治疗后可能会发生局部疾病进展，并且担心手术器械和髓内钉本身可能会沿着髓内管播种肿瘤细胞，最终导致构建体的结构完整性丧失。确定髓内钉稳定后局部疾病进展的相关因素将有助于外科医生预测哪些患者可能受益于替代手术策略。
问题/目的：(1) 在因即将发生或已发生的长骨病理性骨折而接受髓内钉稳定治疗的患者中，局部进展（包括现有病变的进展和钉周围新病变的发展）的风险是多少？(2) 在经历局部进展的患者中，有多少比例需要再次手术？(3) 哪些患者特征和治疗因素与术后局部进展相关？(4) 经历局部进展和局部疾病稳定的患者之间的生存率有何差异？
2013 年 1 月至 2019 年 12 月，我们机构的 177 名患者接受髓内钉治疗即将发生或已发生的病理性骨折。我们排除了在固定前没有病理性转移诊断、年龄小于 18 岁、原发性软组织肿块侵蚀入骨以及因放射骨炎或撕脱性骨折而不是转移导致非愈合的患者。共有 122 名患者符合我们的研究标准。三位接受过骨科肿瘤学培训的外科医生治疗即将发生或病理性骨折，当长骨病变骨折或预计在 3 个月内骨折风险至少为 35%时，以及在预计总生存时间至少为 6 周（骨折）或 3 个月（即将发生）的患者中使用髓内钉，以在其一生中获得姑息性益处。最常见的原发性恶性肿瘤是多发性骨髓瘤（25%[31/122]），其次是肺癌（16%[20/122]）、乳腺癌（15%[18/122]）和肾细胞癌（12%[15/122]）。最常受累的骨骼是股骨（68%[83/122]），其次是肱骨（27%[33/122]）和胫骨（5%[6/122]）。使用竞争风险分析确定患者手术后 1 个月、3 个月、6 个月和 12 个月时进展的风险。计算了最终因进展而需要再次手术的患者比例。进行了单变量分析，以确定病变进展是否与患者年龄和性别、辅助治疗（病变部位的放射治疗、全身治疗和抗吸收治疗）、组织学肿瘤类型、病变位置和骨折类型（即将发生或完全）等各种因素相关。通过 Kaplan-Meier 曲线评估患者生存情况。p 值<0.05 被认为具有统计学意义。
手术后 1 个月、3 个月、6 个月和 12 个月时局部肿瘤进展（以死亡为竞争风险）的累积发生率分别为 1.9%（95%置信区间 0.3%至 6.1%）、2.9%（95%置信区间 0.8%至 7.5%）、3.9%（95%置信区间 1.3%至 8.9%）和 4.9%（95%置信区间 1.8%至 10.3%）。在 122 名患者中，6%（7 名）有髓内钉周围疾病进展，0.8%（1 名）有髓内钉末端新病变。2%（3/122）的患者最终因局部进展而行再次手术。唯一与进展相关的因素是肾细胞癌的原发肿瘤（优势比 5.1[95%置信区间 0.69 至 29]；p=0.03）和患者年龄（平均年龄差异为 7.7 岁[95%置信区间 1.2 至 14]；p=0.02）。我们没有发现局部疾病进展与内脏转移、其他骨骼转移、放射治疗、全身治疗、使用双膦酸盐或核因子κB 配体激活剂抑制剂、骨折类型或钉插入方向之间存在关联。在经历局部进展和局部疾病稳定的患者之间，生存曲线没有差异（=0.36；p=0.54）。
我们的分析表明，对于这组患有骨折或即将发生骨折且预期存活时间至少为 6 周（完全骨折）或 3 个月（即将发生骨折）的转移性骨病患者，髓内钉稳定后发生肿瘤生长和再次手术的局部进展风险似乎较低。尽管这一结论受到当前研究中患者数量较少和生存与局部进展的竞争风险的限制，但病变进展与生存时间无关。根据我们的数据，患有肾细胞癌的患者应避免接受髓内钉治疗，因为术后病变进展的风险较高。
III 级，治疗性研究。
