Do Surgical Margins Affect Local Recurrence and Survival in Extremity, Nonmetastatic, High-grade Osteosarcoma?

BACKGROUND: Long-term survival for all patients with osteosarcoma using current aggressive adjuvant chemotherapy and surgical resection is between 60% and 70%. In patients who present with nonmetastatic, high-grade extremity osteosarcoma of bone, limb salvage surgery is favored, when appropriate, over amputation to preserve the limb, because limb salvage may lead to a superior quality of life compared with amputation. However, concern remains that in the attempt to preserve the limb, close or microscopically positive surgical margins may have an adverse effect on event-free survival. QUESTIONS/PURPOSES: (1) Does a positive or close surgical margin increase the likelihood of a local recurrence? (2) Does a positive or close surgical margin adversely affect the development of metastatic disease? (3) What is the relationship of surgical margin on overall survival? METHODS: With institutional review board approval, we retrospectively evaluated 241 patients treated at our institution between 1999 and 2011. Exclusion criteria included nonextremity locations, metastatic disease at initial presentation, low- or intermediate-grade osteosarcoma, treatment regimens that did not follow National Comprehensive Cancer Network (NCCN) guidelines, incomplete medical records, and any part of treatment performed outside of Moffitt Cancer Center or All Children's Hospital. Fifty-one patients were included in the final analysis, of whom 31 (61%) had followup data at a minimum of 2 years or whose clinical status was known but had died before 2 years of followup. Margin status was defined as (1) microscopically positive; (2) negative ≤ 1 mm; and (3) negative > 1 mm. Margin status, histologic response (tumor percent necrosis), type of osteosarcoma, type of surgery, presence of local recurrence, metastatic disease, and overall survival were recorded for each patient. The mean age was 22 years (range, 12-74 years) and the mean followup was 3 years (range, 0.1-14 years). Margin status was positive in 10% (five of 51), negative ≤ 1 mm 26% (13 of 51), and negative > 1 mm 65% (33 of 51). RESULTS: Local recurrence was noted to be 14% (seven of 51) at 3.4 years. After controlling for relevant confounding variables, the presence of a positive margin compared with a negative margin > 1 mm was the only independent predictor of local recurrence (hazard ratio [HR], 8.006; 95% confidence interval [CI], 1.314-48.781; p = 0.0241). At a mean of 3.4 years, 29% (15 of 51) of the patients developed metastatic disease with no difference with the numbers available in the probability of developing metastatic disease among the three margin groups (p = 0.614). Overall survival at 3.8 years was 75% (38 of 51). After controlling for relevant confounding variables, we found that patients with positive margins were more likely to die from disease than those with negative margins (HR, 6.26; 95% CI, 1.50-26.14; p = 0.0119); no other independent predictors of survival were identified. CONCLUSIONS: With the numbers of patients we had, we observed that patients with extremity, nonmetastatic, high-grade osteosarcoma who had positive margins showed a higher probability of local recurrence in comparison to those with negative surgical margins. Given that positive margins appear to be associated with poorer survival in patients with high-grade osteosarcoma of the extremities, surgeons should strive to achieve negative margins, but larger studies are needed to confirm these findings. LEVEL OF EVIDENCE: Level III, therapeutic study

Hip abductor moment arm - a mathematical analysis for proximal femoral replacement

<p>Abstract</p> <p>Background</p> <p>Patients undergoing proximal femoral replacement for tumor resection often have compromised hip abductor muscles resulting in a Trendelenberg limp and hip instability. Commercially available proximal femoral prostheses offer several designs with varying sites of attachment for the abductor muscles, however, no analyses of these configurations have been performed to determine which design provides the longest moment arm for the hip abductor muscles during normal function.</p> <p>Methods</p> <p>This study analyzed hip abductor moment arm through hip adduction and abduction with a trigonometric mathematical model to evaluate the effects of alterations in anatomy and proximal femoral prosthesis design. Prosthesis dimensions were taken from technical schematics that were obtained from the prosthesis manufacturers. Manufacturers who contributed schematics for this investigation were Stryker Orthopaedics and Biomet.</p> <p>Results</p> <p>Superior and lateral displacement of the greater trochanter increased the hip abductor mechanical advantage for single-leg stance and adduction and preserved moment arm in the setting of Trendelenberg gait. Hip joint medialization resulted in less variance of the abductor moment arm through coronal motion. The Stryker GMRS endoprosthesis provided the longest moment arm in single-leg stance.</p> <p>Conclusions</p> <p>Hip abductor moment arm varies substantially throughout the hip's range of motion in the coronal plane. Selection of a proximal femur endoprosthesis with an abductor muscle insertion that is located superiorly and laterally will optimize hip abductor moment arm in single-leg stance compared to one located inferiorly or medially.</p

Dengue Vaccines Regulatory Pathways: A Report on Two Meetings with Regulators of Developing Countries

Richard Mahoney and colleagues summarize two recent meetings convened by the Pediatric Dengue Vaccine Initiative and the Developing Countries' Vaccine Regulators Network on regulatory issues that need to be addressed before licensing dengue vaccines

Ewing\u2019s Sarcoma of the Sacrum

This book provides an up-to-date overview on the epidemiology, clinical presentation, and imaging characteristics of sacral tumors, discusses the available treatment options, and reports the published outcomes. The diagnostic roles of conventional radiology, CT, and MRI are thoroughly described and imaging appearances are compared with the histologic features. The coverage of therapeutic approaches includes chemotherapy, radiotherapy, radiosurgery, and surgery (partial or total sacrectomy and spinopelvic reconstruction). Special attention is paid to the specific anatomic constraints that make tumors in this region of the spine more difficult to manage effectively than those in the extremities and the mobile portions of the spine All components of the sacrum can give rise to benign or malignant tumors, which pose significant diagnostic and therapeutic challenges. Although these tumors are often diagnosed at an advanced stage, good clinical outcomes may be achieved if an aggressive multidisciplinary approach is used. This book will be of value for a range of practitioners; it will assist in prompt diagnosis and help to overcome lack of familiarity with the required treatment strategies

A Modified Lodwick-Madewell Grading System for the Evaluation of Lytic Bone Lesions

Lodwick's well-established grading system of lytic bone lesions has been widely used in predicting growth rate for lytic bone lesions. We applied a Modified Lodwick-Madewell Grading System as an alternative means to categorize lytic bone tumors into those with low, moderate, and high risks of malignancy. A retrospective review of the radiographs of 183 bone lesions was performed. Cases were selected to include a broad range of benign and malignant tumors. Readers applied our Modified Lodwick-Madewell Grading System, and consensus was reached in all cases. This modified system consists of grade I, which is composed of grades IA and IB as listed in the Lodwick system; grade II, which is grade IC in the Lodwick system; and grade III, which is composed of IIIA (changing margination), IIB (moth-eaten and permeative patterns), and IIIC (radiographically occult). Grading was correlated with the final diagnosis. Of the 183 tumors, 81 were classified as grade I, 54 as grade II, and 48 as grade III. When correlating grade with pathology, we found that 76 of 81 (94%) grade I lesions were benign and 39 of 48 grade III lesions (81%) were malignant. A nearly equal number of grade II lesions proved to be benign (29/54; 54%) and malignant (28/54; 53%). By expanding Lodwick's grading system to include two additional patterns of disease described by Madewell and colleagues (changing margination and radiographically occult) and by reclassifying them into three distinct grades, we propose a modified system-the Modified Lodwick-Madewell Grading System. Application of this system shows correlation of tumor grade with tumor biologic activity and with risk of malignancy: Grade I lesions are usually benign, grade II lesions carry moderate risk of malignancy, and grade III lesions possess a high likelihood of malignancy

Expandable Total Humeral Replacement in a Child with Osteosarcoma

Case. A right-handed 8-year-old female patient presented with a conventional, high-grade osteosarcoma involving her right humerus; through-shoulder amputation was recommended. After consultation, total humerus resection with expandable, total humeral endoprosthesis reconstruction was performed with a sleeve to encourage soft-tissue ingrowth. At three-year follow-up she has received one lengthening procedure and her functional scores are excellent. Conclusion. Total humeral resection and replacement in the pediatric population are rare and although early reports of expandable total humeral endoprosthesis outcomes demonstrate high failure rates, this patient’s success indicates that expandable total humeral replacement is a viable option

Expandable Total Humeral Replacement in a Child with Osteosarcoma

Case. A right-handed 8-year-old female patient presented with a conventional, high-grade osteosarcoma involving her right humerus; through-shoulder amputation was recommended. After consultation, total humerus resection with expandable, total humeral endoprosthesis reconstruction was performed with a sleeve to encourage soft-tissue ingrowth. At three-year follow-up she has received one lengthening procedure and her functional scores are excellent. Conclusion. Total humeral resection and replacement in the pediatric population are rare and although early reports of expandable total humeral endoprosthesis outcomes demonstrate high failure rates, this patient’s success indicates that expandable total humeral replacement is a viable option