David Cheong

Failure Mode Classification for Tumor Endoprostheses: Retrospective Review of Five Institutions and a Literature Review

BACKGROUND Massive endoprostheses provide orthopaedic oncologists with many reconstructive options after tumor resection, although failure rates are high. Because the number of these procedures is limited, failure of these devices has not been studied or classified adequately. This investigation is a multicenter review of the use of segmental endoprostheses with a focus on the modes, frequency, and timing of failure. METHODS Retrospective reviews of the operative databases of five institutions identified 2174 skeletally mature patients who received a large endoprosthesis for tumor resection. Patients who had failure of the endoprosthesis were identified, and the etiology and timing of failure were noted. Similar failures were tabulated and classified on the basis of the risk of amputation and urgency of treatment. Statistical analysis was performed to identify dependent relationships among mode of failure, anatomic location, and failure timing. A literature review was performed, and similar analyses were done for these data. RESULTS Five hundred and thirty-four failures were identified. Five modes of failure were identified and classified: soft-tissue failures (Type 1), aseptic loosening (Type 2), structural failures (Type 3), infection (Type 4), and tumor progression (Type 5). The most common mode of failure in this series was infection; in the literature, it was aseptic loosening. Statistical dependence was found between anatomic location and mode of failure and between mode of failure and time to failure. Significant differences were found in the incidence of failure mode Types 1, 2, 3, and 4 when polyaxial and uniaxial joints were compared. Significant dependence was also found between failure mode and anatomic location in the literature data. CONCLUSIONS There are five primary modes of endoprosthetic failure, and their relative incidences are significantly different and dependent on anatomic location. Mode of failure and time to failure also show a significant dependence. Because of these relationships, cumulative reporting of segmental failures should be avoided because anatomy-specific trends will be missed. Endoprosthetic design improvements should address failure modes specific to the anatomic location.

Combination of External Beam Radiotherapy (EBRT) With Intratumoral Injection of Dendritic Cells as Neo-Adjuvant Treatment of High-Risk Soft Tissue Sarcoma Patients

PURPOSE The goal of this study was to determine the effect of combination of intratumoral administration of dendritic cells (DC) and fractionated external beam radiation (EBRT) on tumor-specific immune responses in patients with soft-tissue sarcoma (STS). METHODS AND MATERIAL Seventeen patients with large (>5 cm) high-grade STS were enrolled in the study. They were treated in the neoadjuvant setting with 5,040 cGy of EBRT, split into 28 fractions and delivered 5 days per week, combined with intratumoral injection of 10(7) DCs followed by complete resection. DCs were injected on the second, third, and fourth Friday of the treatment cycle. Clinical evaluation and immunological assessments were performed. RESULTS The treatment was well tolerated. No patient had tumor-specific immune responses before combined EBRT/DC therapy; 9 patients (52.9%) developed tumor-specific immune responses, which lasted from 11 to 42 weeks. Twelve of 17 patients (70.6%) were progression free after 1 year. Treatment caused a dramatic accumulation of T cells in the tumor. The presence of CD4(+) T cells in the tumor positively correlated with tumor-specific immune responses that developed following combined therapy. Accumulation of myeloid-derived suppressor cells but not regulatory T cells negatively correlated with the development of tumor-specific immune responses. Experiments with (111)In labeled DCs demonstrated that these antigen presenting cells need at least 48 h to start migrating from tumor site. CONCLUSIONS Combination of intratumoral DC administration with EBRT was safe and resulted in induction of antitumor immune responses. This suggests that this therapy is promising and needs further testing in clinical trials design to assess clinical efficacy.

Orthopedic surgery options for the treatment of primary osteosarcoma.

BACKGROUND Osteosarcoma is the most common malignant primary neoplasm of bone. Orthopedic procedures are essential components in the multidisciplinary treatment of osteosarcoma. Limb-salvaging procedures offer adequate disease control comparable to the results obtained by amputations. This review discusses the advantages and disadvantages of the various types of amputations and the limb-salvaging techniques for the treatment of osteosarcoma. METHODS The authors analyzed the characteristics of limb-salvaging procedures and amputations for osteosarcoma. Qualitative and quantitative studies published in the English language that are listed in the National Library of Medicine were used as the basis for this review. In addition, a review of an expandable prosthesis is included. RESULTS Limb-salvaging techniques have acceptable rates of disease control. However, amputation remains a valid procedure in selected cases of osteosarcoma in most parts of the world. Orthopedic oncology surgeons have various materials, procedures, and techniques available to achieve disease control and improve function in patients with osteosarcoma. CONCLUSIONS The surgical management of patients with osteosarcoma is challenging. No difference in survival has been shown between amputations and adequately performed limb-salvaging procedures. Optimal tumor resection and a functional residual limb with increased patient survival are the goals of modern orthopedic oncology.

Advances in Segmental Endoprosthetic Reconstruction for Extremity Tumors: A Review of Contemporary Designs and Techniques

BACKGROUND Improved understanding and advances in treatment regimens have led to increased longevity among patients diagnosed with extremity soft tissue sarcomas. Limb salvage techniques and implants have improved and continue to evolve to accommodate the increasing demands and survival of these patients. METHODS The current report is a review of the literature for recent advancements in techniques, implant design, and outcomes in the field of limb salvage therapy using segmental megaprostheses for the treatment of extremity sarcomas. We report on our experience in this field utilizing a classification system of failure mechanisms to outline to discuss current controversies in management. RESULTS Five mechanisms of failure have been identified: soft-tissue failure, aseptic loosening, structural failure, infection, and tumor progression. Infection was the most common mode of failure in our series, accounting for 34% of cases. Soft-tissue failure occurred most commonly in the joints that depend heavily on periarticular muscles and ligaments for stability due to their high degree of functional range of motion. We observed a 28% soft-tissue failure rate about the shoulder and hip, aseptic loosening accounted for 19% of implant failures, and structural failure was seen in 17% of cases. Seventeen percent of cases failed due to tumor progression, an etiology that is defined by biological factors, surgical technique, and adjuvant therapies. CONCLUSIONS Surgical techniques and megaprosthesis designs are constantly changing in order to meet the challenge of increasing functional demands and longevity in this unique patient population. A classification system defined by treatment failure etiologies provides the framework for discussion of current controversies in limb salvage therapy as well as a guide for advancement and potential solutions in this challenging arena.

Outcome of lower-limb preservation with an expandable endoprosthesis after bone tumor resection in children.

BACKGROUND The optimal treatment of malignant pediatric lower-extremity bone tumors is controversial. Expandable endoprostheses allow limb preservation, but the revision rate and limited function are considered barriers to their use. This study investigated the functional, emotional, and oncologic outcomes of thirty-eight patients treated with an expandable endoprosthesis. METHODS A retrospective chart review was performed, and surviving patients were asked to complete the Musculoskeletal Tumor Society (MSTS) outcomes instrument and the Pediatric Outcomes Data Collection Instrument (PODCI). Additional data including the range of hip and knee motion, limb-length discrepancy, and total lengthening were also obtained. RESULTS Thirty-eight patients were treated with an expandable endoprosthesis, and twenty-six of these patients were alive at the time of the study. The mean global MSTS score was 26.1, and the mean global PODCI score was 85.8. The mean emotional acceptance and happiness subscores were high. The mean sagittal-plane hip motion in patients who had undergone replacement of the proximal aspect of the femur was 103°. The mean knee motion in patients who had undergone replacement of the proximal aspect of the femur, the distal aspect of the femur, or the proximal aspect of the tibia was 127°, 97°, and 107°, respectively. The mean lengthening at the time of skeletal maturity was 4.5 cm, and the mean limb-length discrepancy was 0.7 cm. Forty-two percent of the patients experienced complications, with ten patients requiring prosthesis revision and two of these patients requiring amputation. CONCLUSIONS Current technology does not offer a single best reconstruction option for children. Previous studies and the present series have indicated that physical and emotional functioning in patients treated with an expandable endoprosthesis are good but that complication rates remain high. Amputation and rotationplasty are alternative treatments if patients and their families are amenable to these procedures. The literature supports no single superior treatment among these three options with regard to physical or emotional health.

Computer-Assisted Navigation and Musculoskeletal Sarcoma Surgery

BACKGROUND Despite advances in medical, surgical, and radiation oncology, deep-seated bone sarcomas that require large osseous resections continue to present resection and reconstructive challenges to musculoskeletal surgeons. METHODS We describe our experience with computer navigation techniques combined with complex pelvic resections and limb-preserving surgeries. RESULTS Computer-assisted navigation has shown promise in aiding in optimal preoperative planning and in providing more accurate and precise feedback during surgery. CONCLUSIONS Computer-assisted navigation offers precise instrumentation, technology-oriented imaging systems, and powerful information processing, all of which can assist in decision making, preoperative planning, and surgical accuracy.

Practical issues of intraoperative frozen section diagnosis of bone and soft tissue lesions.

BACKGROUND Intraoperative pathologic diagnosis of bone and soft tissue lesions is an important yet challenging tool in clinical musculoskeletal oncology practice. There is limited information in the literature addressing the practical issues commonly encountered regarding intraoperative frozen section of musculoskeletal lesions. METHODS A literature review and retrospective review of practical experience in intraoperative pathology consultation at our institutes sarcoma program were conducted to investigate the pitfalls and limitations of frozen section and potential solutions to overcome these problems. RESULTS Frozen section evaluation is an essential and reliable procedure for guiding intraoperative decisions. Intraoperative cytology as an adjunct to frozen section enhances the accuracy of diagnosis of bone and soft tissue lesions. Cytology can accurately diagnose certain entities alone and is superior to frozen section for certain tumor types and for evaluating bone marrow margins. It is also invaluable in triaging cases for ancillary studies and for tumor banking. Practical working protocols can be developed to optimize the usefulness of intraoperative pathologic consultation. CONCLUSIONS Intraoperative pathology consultation should be done in an interdisciplinary approach by correlating clinical, radiologic, and pathologic information. As an adjunct to frozen section, cytology and gross examination enhance the accuracy of diagnosis of musculoskeletal lesions.

Limb Preservation With Isolated Limb Infusion for Locally Advanced Nonmelanoma Cutaneous and Soft-Tissue Malignant Neoplasms

OBJECTIVE To demonstrate the efficacy of isolated limb infusion (ILI) in limb preservation for patients with locally advanced soft-tissue sarcomas and nonmelanoma cutaneous malignant neoplasms. BACKGROUND Locally advanced nonmelanoma cutaneous and soft-tissue malignant neoplasms, including soft-tissue sarcomas of the extremities, can pose significant treatment challenges. We report our experience, including responses and limb preservation rates, using ILI in cutaneous and soft-tissue malignant neoplasms. METHODS We identified 22 patients with cutaneous and soft-tissue malignant neoplasms who underwent 26 ILIs with melphalan and dactinomycin from January 1, 2004, through December 31, 2009, from 5 institutions. Outcome measures included limb preservation and in-field response rates. Regional toxic effects were measured using the Wieberdink scale and serum creatinine phosphokinase levels. RESULTS The median age was 70 years (range, 19-92 years), and 12 patients (55%) were women. Fourteen patients (64%) had sarcomas, 7 (32%) had Merkel cell carcinoma, and 1 (5%) had squamous cell carcinoma. The median length of stay was 5.5 days (interquartile range, 4-8 days). Twenty-five of the 26 ILIs (96%) resulted in Wieberdink grade III or less toxicity, and 1 patient (4%) developed grade IV toxicity. The median serum creatinine phosphokinase level was 127 U/L for upper extremity ILIs and 93 U/L for lower extremity ILIs. Nineteen of 22 patients (86%) underwent successful limb preservation. The 3-month in-field response rate was 79% (21% complete and 58% partial), and the median follow-up was 8.6 months (range, 1-63 months). Five patients underwent resection of disease after an ILI, of whom 80% are disease free at a median of 8.6 months. CONCLUSIONS Isolated limb infusion provides an attractive alternative therapy for regional disease control and limb preservation in patients with limb-threatening cutaneous and soft-tissue malignant neoplasms. Short-term response rates appear encouraging, yet durability of response is unknown.

Cutaneous leiomyosarcoma: Treatment and outcomes with a standardized margin of resection

BACKGROUND Cutaneous leiomyosarcoma is primarily a low-grade malignancy that affects elderly male Caucasians. It is a rare dermal-based tumor for which treatment algorithms have been poorly defined. METHODS We retrospectively reviewed the use of a median 1-cm margin for resection to treat patients with cutaneous leiomyosarcoma referred for treatment between 2005 and 2010. RESULTS Thirty-three patients with cutaneous leiomyosarcoma were treated. Of these, 76% were male, 97% were Caucasian (median age: 63.5 years), and 67% of tumors were located on the extremities. Preoperative staging was negative for distant metastasis in all patients. A majority of the tumors (88%) were low grade (median size: 1.3 cm). All of the tumors were positive for smooth-muscle actin. A total of 94% of patients underwent primary surgical resection with a median margin of 1 cm. Final resection margin was negative in 97% of patients. Adjuvant radiotherapy was used in 15%. No metastatic spread or recurrences were present, and 100% of patients were alive at last follow-up (median: 15.5 months). CONCLUSIONS Good oncological control and excellent outcomes are possible with a 1-cm resection margin in most cases of cutaneous leiomyosarcoma.

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

AbstractBackground 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?MethodsWith 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).ResultsLocal 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.ConclusionsWith 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 EvidenceLevel III, therapeutic study.