Background 

Cemented endoprosthetic reconstruction after resection of primary bone sarcomas has been in common use for decades. Although multiple studies have reported the survivorship of primary endoprostheses, implant survivorship after revision surgery is less well established. Given that earlier advances in systemic therapy improved survival of patients with sarcoma, the usage of revision endoprostheses can be expected to increase and, as such, understanding revision implant survivorship will help to inform patient and surgeon expectations. Additionally, as new implants are developed that allow alternative reconstruction options, a normative dataset establishing accurate expectations for revision cemented endoprostheses is a critical benchmark by which to measure progress.

Questions/purposes 

(1) What is the implant survivorship free of all-cause revision for primary and revision cemented distal femoral replacements (DFRs) used in the treatment of malignant or benign tumors? (2) What are the most common indications for revision of primary and revision DFRs in an oncology population with mean follow-up of more than 10 years? (3) How does the indication for revision of a primary DFR affect the subsequent risk for and type of revision DFR complication? (4) What patient, tumor, or implant characteristics are associated with improved survivorship free of revision in cemented DFRs used in patients treated initially for primary malignant or benign tumors?

Methods 

This was a retrospective, comparative study using our institution’s longitudinally-maintained database of 806 cemented endoprostheses starting in 1980 and assessed through December 31, 2018. In all, 365 DFRs were inserted during this time, but 14% (51 of 365) were placed for nonprimary bone tumors and 1% (5 of 365) were cementless reconstructions, leaving 309 cemented DFRs. Seventy-one percent (218 of 309) were primary implants and 29 percent (91 of 309) were revision implants (used to revise a prior DFR in all patients). During this time period, our strong bias was to use cemented stems and, thus, nearly all of our patients had cemented stems. Six percent (13 of 218) of primary DFRs were implanted more than 2 years before the study end; however, they lacked 2 years of follow-up data and, thus, were considered lost to follow-up, leaving 205 implants in the primary DFR analysis group. Only the first revision after primary DFR revision surgery was included in the revision cohort analysis. Thirty-two percent (29 of 91) of revision DFRs were second or more revision patients and were excluded, leaving 62 implants in the revision analysis group. Most patients in both groups were men (57% [117 of 205] for primary and 71% [44 of 62] for revision) who had been diagnosed with osteosarcoma (75% [153 of 205] and 73% [45 of 62] for primary and revision, respectively). The primary cohort had mean age of 26 ± 16 years with a mean follow-up of 136 ± 122 months, and the revision cohort had mean age of 31 ± 13 years (p = 0.02) with 141 ± 101 months of follow-up. Study endpoints included all-cause implant revision and cause-specific revision for soft tissue complications, aseptic loosening, structural complications (defined as periprosthetic or implant fracture), infection, or tumor progression. Planned surgery for implant lengthening procedures was excluded. Implant survivorship free from all-cause revision was calculated using a competing risk (cumulative incidence) estimator with death as a competing risk. A log-rank test using chi-square analysis was used to evaluate the differences in implant survivorship between primary DFRs and first revisions. The cause-specific incidences of implant revision were tabulated for primary and revision DFRs. Cox regression analysis investigated the odds of subsequent all-cause revision surgery for revision cemented DFRs based on the primary implant complication. A binary logistic regression analysis using age, gender, indication for revision, tumor type, infection, perioperative chemotherapy, and radiation was performed to identify factors associated with a second DFR reoperation. Relative effect sizes are reported as ORs.

Results 

The revision DFR cohort had a shorter mean survival to all-cause revision than the primary cohort (mean 10 years [95% CI 7 to 12] versus 18 years [95% CI 15 to 20]; p < 0.001). The most common complications necessitating revision for revision implants were periprosthetic or implant fracture in 37% (23 of 62) and aseptic loosening in 15% (9 of 62), and the type of primary implant complication was not associated with risk of subsequent all-cause revision surgery for revision implants. Stem diameter less than 15 mm was associated with repeat all-cause revision in cemented revision DFRs after controlling for resection length, stem length, implant fabrication (custom or modular), and presence of a porous collar (OR 4 [95% CI 1 to 17]; p = 0.03). No other parameters that we explored, including patient age, gender, chemoradiation history, or primary tumor diagnosis, were associated with repeat revision surgery.

Conclusion 

Understanding modifiable factors that can improve revision DFR survival is critical to achieving long-term limb salvage for patients with tumors around the knee. Our data suggest that utilizing implants with the largest possible stems—or at a minimum increasing the stem size over the primary implant—is important to revision cemented DFR survivorship and is an important part of our revision practice. Improving revision implants’ resistance to aseptic loosening through designs that resist torsion (a common mode of cemented fixation failure)—such as with the use of custom cross-pin fabrication—may be one method to improve survivorship. Another will be improved implant metallurgy that is resistant to fatigue fracture. Next steps may include understanding the optimal ratio of femoral diaphyseal width to implant diameter in patients where anatomic constraints preclude the insertion of cemented stems 15 mm or more in diameter.

Level of Evidence 

Level IV, therapeutic study.

中文翻译：

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肉瘤患者保肢初次和翻修骨水泥远端股骨置换术的长期生存率是多少？

 背景

原发性骨肉瘤切除后的骨水泥内假体重建已普遍使用数十年。尽管多项研究报告了初次内置假体的存活率，但翻修手术后植入物的存活率尚不清楚。鉴于系统治疗的早期进展提高了肉瘤患者的生存率，翻修内置假体的使用预计会增加，因此，了解翻修植入物的生存率将有助于告知患者和外科医生的期望。此外，随着允许替代重建选项的新植入物的开发，建立修正骨水泥内置假体的准确期望的规范数据集是衡量进展的关键基准。

 问题/目的

(1) 用于治疗恶性或良性肿瘤的初次和翻修骨水泥远端股骨置换术 (DFR) 的植入物存活率是多少？ (2) 在平均随访时间超过 10 年的肿瘤人群中，修订初次 DFR 和修订 DFR 的最常见指征是什么？ (3) 原发性 DFR 修正的指征如何影响后续 DFR 修正并发症的风险和类型？ (4) 哪些患者、肿瘤或植入物特征与最初治疗原发性恶性肿瘤或良性肿瘤的患者中使用的骨水泥 DFR 无需翻修而改善的生存率相关？

 方法

这是一项回顾性比较研究，使用了我们机构自 1980 年开始纵向维护的 806 个骨水泥内假体数据库，截至 2018 年 12 月 31 日进行了评估。在此期间总共插入了 365 个 DFR，但仅放置了 14%（365 个中的 51 个）对于非原发性骨肿瘤，1%（365 例中的 5 例）采用无骨水泥重建，剩下 309 例骨水泥 DFR。 71%（309 例中的 218 例）是初次种植体，29%（309 例中的 91 例）是修正种植体（用于修正所有患者之前的 DFR）。在此期间，我们强烈倾向于使用骨水泥柄，因此，几乎所有患者都使用骨水泥柄。百分之六（218 例中的 13 例）的原发性 DFR 是在研究结束前 2 年多植入的；然而，他们缺乏 2 年的随访数据，因此被认为失访，在主要 DFR 分析组中留下了 205 个种植体。仅初次 DFR 翻修手术后的第一次翻修纳入翻修队列分析中。 32%（91 例中的 29 例）翻修 DFR 是第二次或更多翻修患者，因此被排除在外，在翻修分析组中留下 62 个种植体。两组中的大多数患者均为男性（原发患者为 57% [205 人中的 117 人]，翻修患者为 71% [62 人中的 44 人]），他们被诊断为骨肉瘤（75% [205 人中的 153 人] 和 73% [62 人中的 45 人]分别用于初级和复习）。主要队列的平均年龄为 26 ± 16 岁，平均随访时间为 136 ± 122 个月，修正队列的平均年龄为 31 ± 13 岁 (p = 0.02)，随访时间为 141 ± 101 个月。 研究终点包括全因种植体修正和针对软组织并发症、无菌性松动、结构并发症（定义为假体周围或种植体断裂）、感染或肿瘤进展的特定原因修正。计划进行的种植体延长手术被排除在外。使用竞争风险（累积发生率）估计器（以死亡作为竞争风险）计算免于全因翻修的种植体存活率。使用卡方分析进行对数秩检验来评估初次 DFR 和首次修订之间种植体存活率的差异。将初次和翻修 DFR 的种植体翻修的具体原因发生率制成表格。 Cox 回归分析根据主要种植体并发症调查了随后进行全因翻修手术以修复骨水泥 DFR 的可能性。使用年龄、性别、翻修指征、肿瘤类型、感染、围手术期化疗和放疗进行二元逻辑回归分析，以确定与第二次 DFR 再次手术相关的因素。相对效应大小以 OR 报告。

 结果

与主要队列相比，DFR 翻修队列的全因翻修平均生存期较短（平均 10 年 [95% CI 7 至 12] 与 18 年 [95% CI 15 至 20]；p < 0.001）。需要对修复种植体进行修复的最常见并发症是假体周围或种植体断裂，占 37%（62 例中的 23 例），无菌性松动占 15%（62 例中的 9 例），并且主要种植体并发症的类型与随后发生所有并发症的风险无关。进行修复植入物的修复手术。在控制切除长度、柄长度、种植体制造（定制或模块化）和多孔颈圈的存在后，柄直径小于 15 mm 与骨水泥翻修 DFR 中的重复全因修复相关（OR 4 [95% CI 1 至17]；p = 0.03）。我们探索的其他参数，包括患者年龄、性别、放化疗史或原发肿瘤诊断，均与重复修复手术无关。

 结论

了解可改善翻修 DFR 存活率的可改变因素对于膝关节周围肿瘤患者实现长期保肢至关重要。我们的数据表明，使用具有尽可能大的茎的种植体，或者至少增加主种植体的茎尺寸，对于修复骨水泥 DFR 存活率非常重要，也是我们修复实践的重要组成部分。通过抗扭转（骨水泥固定失败的常见模式）设计（例如使用定制的十字销制造）来提高修复种植体对无菌性松动的抵抗力，可能是提高存活率的一种方法。另一个是改进植入物冶金学，使其具有抗疲劳断裂的能力。下一步可能包括了解因解剖学限制而无法插入直径为 15 毫米或以上的骨水泥柄的患者的股骨骨干宽度与植入物直径的最佳比率。

 证据水平

IV级，治疗研究。