Where Are We Now?
Despite decades of clinical practice and research, reconstruction following tumor resections in the long bones remains a challenge, particularly in treating young patients who have considerable growth remaining.
The study by Aponte-Tinao and colleagues adds to our overall understanding of using structural allografts to recreate skeletal integrity following the resection of bone sarcomas. In children younger than 10 who were treated for either Ewing’s sarcoma or osteosarcoma, allograft reconstruction was shown to provide a viable treatment option even after surgeons removed an involved physis. Their patients developed expected but manageable limb-length inequalities. In addition, many children experienced complications resulting in more surgery. The authors demonstrated that the large majority of these allografts remained in service at longer-term followup.
Results from this and other studies, using a variety of reconstruction techniques [1, 3, 7, 9, 11] suggest that limb salvage is a safe alternative to amputation [10, 12]. Nonetheless, these reports also recognize a high risk of prosthesis or graft-related complication such as nonunion, fracture, infection, subsequent revision surgery, and other secondary operations in these patients. Expandable prostheses, used to provide lengthening of the limb for patients with expected skeletal growth, also are associated with frequent complications [2, 4]. Recently reported reconstruction of long bone defects employing a modified use of the induced-membrane bone grafting technique proved effective in some children following sarcoma resection, but this technique also was associated with a high risk of complications and secondary surgical procedures, and may not be appropriate for patients with with growth remaining . Thus, the current state of the art of limb preservation for these two osseous malignancies—treatment with chemotherapy, resection, and limb reconstruction—seems generally but not universally successful. The ideal reconstructive approach remains controversial, in light of the known drawbacks of each approach.
Where Do We Need To Go?
As I was preparing this commentary, a patient of mine returned to clinic for long-term followup of a Ewing sarcoma diagnosed more than 25 years ago when she was 9. This 35-year-old woman just underwent a successful heart transplantation for chemotherapy-related cardiomyopathy and advanced congestive heart failure following the delivery of her first child. Her right femur, which had initially been treated with resection and an intercalary allograft reconstruction, had been retained and the limb, although 5 cm short (similar to the patients reported in the current study) was functional for ambulation. Considering the initial diagnosis and presentation, the result could be considered a clear success. Briefly recounting her medical history, however, is illustrative. She initially presented with a mid-shaft pathological femur fracture, and she was treated with preoperative chemotherapy (first, while hospitalized in skeletal traction and later, in a spica cast) with a good clinical response. Following resection of the tumor, the femur was reconstructed with an allograft, stabilized (because of her small stature) with an intramedullary humeral nail. Subsequent procedures were performed to graft a distal-junction nonunion and, 5 years later, a fatigue fracture of the proximal allograft-host junction. A proximal femoral osteotomy, and later, conversion to a proximal femoral implant (cemented through the allograft) were performed in her teens, and, as a young adult, 20 years after the initial surgery, she underwent a total hip arthroplasty for progressive acetabular wear. Looking at the overall result, the original allograft is still in place and the limb preserved with a substantial limb length deficit but “acceptable function.” To get to this point, though, the treatment for her sarcoma has resulted in extensive and repeated surgical procedures and the medication-related, near-fatal heart injury has resulted in cardiac transplantation with lifelong immunosuppression and medically imposed activity restrictions. Important as well is the limitation of her right leg function. The soft tissues of the operated limb remain smaller and the leg weaker than the contralateral or “normal limb”, which itself has, over the years developed increasing ligamentous laxity, arthritis, and a varus deformity of 10°. As one can see from this story, “success” in this context depends on the metrics we use to define it.
We need rigorous, validated, and consistent approaches to assessing function, patient satisfaction, and perhaps even the economic, social, and psychological impacts of the complications associated with the treatments we use when caring for children diagnosed with musculoskeletal cancers.
How Do We Get There?
Carefully performed evaluations, with sufficient long-term followup of patients who have received a consistent treatment protocol for rare childhood malignancies, such as those reviewed in this article, remain important. However, the common difficulties of single-institution studies include heterogeneity of clinical presentations and the rarity of the tumors. Small sample sizes and numerous uncontrolled variables further confound comparisons across series of this type, especially when evaluating different reconstructive techniques. National or specialty societies may have the opportunity to collaborate, but funding and logistical constraints make this difficult.
Cooperative group trials, such as those coordinated through the Children’s Oncology Group (childrensoncologygroup.org) and other national or international consortia have the theoretical advantage of evaluating a much greater number of patients by accumulating data across multiple institutions. In the past, cooperative groups studying childhood cancer have provided important information through controlled trials demonstrating the profound advantage of chemotherapy in osteosarcoma treatment . Other cooperative groups’ studies have attempted to answer surgical questions, such as the potential benefit of surgery in Ewing’s sarcoma by utilizing retrospective evaluation of a prospectively accumulated database and complex statistical analysis . Although there are drawbacks in research conducted within such multi-institutional cooperative groups, it is encouraging that, unlike adult patients, most children with cancer are enrolled in clinical trials sponsored by institutions participating in large national or international cooperative groups. As such, this forum has the potential to provide surgeons the opportunity to be involved in research programs, to formulate surgical research questions, and to recommend what clinically important information that should be prospectively collected. By incorporating clinical followup information in the protocols, surgical studies could be designed to address the as-yet unanswered questions about durability, long-term function, and complications that result in additional surgery after skeletal reconstruction in children.
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