Limb Amputations in Cancer: Modern Perspectives, Outcomes, and Alternatives.

PURPOSE OF REVIEW: This review summarizes current findings regarding limb amputation within the context of cancer, especially in osteosarcomas and other bony malignancies. We seek to answer the question of how amputation is utilized in the contemporary management of cancer as well as explore current advances in limb-sparing techniques. RECENT FINDINGS: The latest research on amputation has been sparse given its extensive history and application. However, new research has shown that rotationplasty, osseointegration, targeted muscle reinnervation (TMR), and regenerative peripheral nerve interfaces (RPNI) can provide patients with better functional outcomes than traditional amputation. While limb-sparing surgeries are the mainstay for managing musculoskeletal malignancies, limb amputation is useful as a palliative technique or as a primary treatment modality for more complex cancers. Currently, rotationplasty and osseointegration have been valuable limb-sparing techniques with osseointegration continuing to develop in recent years. TMR and RPNI have also been of interest in the modern management of patients requiring full or partial amputations, allowing for better control over myoelectric prostheses.

Intraoperative Localization Using an Implanted Radar Reflector Facilitates Resection of Non-Palpable Trunk and Extremity Sarcoma.

BACKGROUND: Resecting non-palpable soft tissue tumors presents a unique challenge, particularly with recurrent disease in which surrounding tissue has been surgically manipulated and often irradiated. SAVI SCOUT® is a radar-based localization device that was developed for breast tumor localization and was recently FDA-approved for localization of soft tissue tumors. Application of this technology to soft tissue sarcoma has not been previously reported. METHODS: We assembled a single-institution retrospective case series of patients with trunk and extremity sarcomas resected by five sarcoma surgeons using SAVI SCOUT® from December 2018 to May 2020. Reflectors were placed preoperatively using image-guidance, and the radar detector was used intraoperatively to localize the target lesion. Clinical variables were abstracted from the electronic medical record including treatment history, pathology, and early oncologic outcomes. Using a focused review, we compared margin status and recurrence rates with previously published cohorts. RESULTS: Ten SAVI SCOUT®-localized sarcoma resections were performed. Eight were for locally recurrent disease, of which seven (83%) had prior radiation. The remaining lesions became non-palpable after neoadjuvant chemotherapy. SAVI SCOUT® facilitated resection in all cases with a margin-negative resection rate (77%) comparable to prior cohorts. In this high-risk population with a median follow-up of 14 months, only one patient recurred locally 7.5 months after SAVI SCOUT®-localized resection, requiring re-resection. CONCLUSION: SAVI SCOUT® technology facilitated resection of non-palpable recurrent sarcoma of the trunk and extremities in all ten cases attempted. In a high-risk patient population, the pattern of recurrence has been primarily distant with one instance of local tumor recurrence.

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

OBJECTIVE: 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. MATERIALS AND METHODS: 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. RESULTS: 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%). CONCLUSION: 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.

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.

What are the results using the modified trapdoor procedure to treat chondroblastoma of the femoral head?

BACKGROUND: Treatment of chondroblastoma in the femoral head is challenging owing to the particular location and its aggressive nature. There is little published information to guide the surgeon regarding the appropriate approach to treating a chondroblastoma in this location. We developed a modified trapdoor procedure to address this issue. The primary modification is that the window surface of the femoral head is covered by the ligamentum teres rather than cartilage as in the traditional procedure. QUESTIONS/PURPOSES: We assessed (1) the clinical presentation of chondroblastoma of the femoral head and treatment results with the modified trapdoor procedure in terms of (2) the frequency of local recurrence, (3) complications, and (4) functional outcomes using the Musculoskeletal Tumor Society (MSTS) score. METHODS: Between 1999 and 2010, we treated 14 patients for chondroblastoma of the femoral head. All patients received the modified trapdoor procedure. Of those, 13 were available for followup at a minimum of 36 months (mean, 66 months; range, 36-117 months) and one patient was lost to followup. There were nine males and four females, with a mean age of 18 years (range, 9-29 years). Clinical features were ascertained by chart and radiographic review, and recurrence, complications, and functional outcomes (MSTS score) were recorded from chart review. Patterns of bone destruction were evaluated using the Lodwick classification, which ranges from IA (geographic appearance with sclerotic rim) to III (permeative appearance). RESULTS: The symptoms at diagnosis were pain in nine patients and discomfort in four. The mean duration of symptom was 11 months (range, 1-36 months). The physis was open in two patients, closing in one, and closed in 10. The patterns of bone destruction were evaluated as Lodwick Class IA in six patients, Lodwick Class IB in five, and Lodwick Class IC in two. At latest followup, no local recurrence was observed. Two patients had postoperative complications. One had avascular necrosis of the femoral head and was treated with prosthesis replacement. The other had asymptomatic heterotopic ossification in the surgical field. The mean MSTS score was 29.6 (range, 28-30). CONCLUSIONS: Based on this small series, we believe our modified trapdoor procedure is a safe, effective means of treating a chondroblastoma in the femoral head, but additional clinical evaluation with more patients is necessary to confirm our findings. LEVEL OF EVIDENCE: Level IV, therapeutic study. See the Instructions for Authors for a complete description of levels of evidence.

Management of bone disease with concurrent chimeric antigen receptor T-cell therapy for multiple myeloma.

In the intricate landscape of multiple myeloma, a hematologic malignancy of plasma cells, bone disease presents a pivotal and often debilitating complication. The emergence of Chimeric Antigen Receptor T-cell (CAR-T) therapy has marked a pivotal shift in the therapeutic landscape, offering novel avenues for the management of MM, particularly for those with relapsed or refractory disease. This innovative treatment modality not only targets malignant cells with precision but also influences the bone microenvironment, presenting both challenges and opportunities in patient care. In this comprehensive review, we aim to examine the multifaceted aspects of bone disease in patients with multiple myeloma and concurrent CAR-T therapy, highlighting its clinical ramifications and the latest advancements in diagnostic modalities and therapeutic interventions. The article aims to synthesize current understanding of the interplay between myeloma cells, CAR-T cells, and the bone microenvironment in the context of current treatment strategies in this challenging and unique patient population.

Cutaneous angiosarcoma: a single-institution experience.

BACKGROUND: Cutaneous angiosarcoma (CAS) is a rare, aggressive vascular sarcoma with a poor prognosis, historically associated with 5-year overall survival (OS) rates between 10 and 30 %. METHODS: This is a single-institution retrospective review of patients treated for CAS from 1999-2011. Demographics, primary tumor characteristics, treatment, and outcomes were analyzed. RESULTS: A total of 88 patients were identified (median age 70 years and 57 % female). Median tumor size was 3 cm. Median follow-up was 22 months. The 5-year OS and recurrence-free survival (RFS) were 35.2 and 32.3 %, respectively; median was 22.1 months. Also, 36 patients (41 %) received surgery alone, 7 (8 %) received XRT alone, and 41 (47 %) received surgery and XRT. Of the 67 of 88 patients who were disease-free after treatment, 33 (50 %) recurred (median of 12.3 months). Surgery alone had the highest 5-year OS (46.9 %) and RFS (39.9 %) (p = ns). Four presentation groups were identified: (1) XRT-induced, n = 30 (34 %), 26 of 30 occurred in females with a prior breast cancer, (2) sporadic CAS on head and neck (H/N), n = 38, (3) sporadic CAS on trunk/extremities, n = 13, and (4) Stewart-Treves n = 7. Those with trunk/extremity CAS had the highest 5-year OS (64.8 %), with H/N CAS having the worst 5-year OS (21.5 %). On MV analysis, only tumor size <5 cm correlated with improved OS (p = 0.014). DISCUSSION: In this large series, there appears to be a better overall prognosis than historically reported, especially in Stewart-Treves and CAS on trunk or extremities. While surgery alone was associated with better OS and RFS compared with other treatment modalities, this was not statistically significant. Tumor size was a significant prognostic factor for OS.

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.

Adult soft tissue sarcoma local recurrence after adjuvant treatment without resection of core needle biopsy tract.

BACKGROUND: Core needle biopsies of sarcomas allow a diagnosis in a high percentage of patients with few complications. However, it is unclear whether the tract needs to be excised to prevent recurrences. QUESTIONS/PURPOSES: We therefore determined the rates of recurrence and metastases in patients with Stage III extremity sarcomas, who underwent wide local resection without excision of the needle tract and also received adjuvant treatment. METHODS: We retrospectively reviewed 59 adult patients with deep, larger than 5 cm, high-grade soft tissue sarcomas of the upper or lower extremity treated between January 1999 and April 2009. All the patients underwent a core needle biopsy. Resection was performed with wide margins. The biopsy tract was not resected during the definitive surgery. Fifty-seven patients (97%) received preoperative and/or postoperative radiation, whereas 49 patients (83%) received chemotherapy. Local recurrence and distant recurrence rates were determined. The minimum followup was 24 months (median, 56 months; range, 24-122 months). RESULTS: The local recurrence rate was 9%. Fifteen patients (25%) developed metastasis after diagnosis. Seven of the 59 patients (12%) had microscopic positive margins at resection. CONCLUSIONS: Our data demonstrate no increase in local recurrence rates or rates of metastatic disease compared with previously published studies when resection of the core biopsy tract was not performed. LEVEL OF EVIDENCE: Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.

The role of radical amputations for extremity tumors: a single institution experience and review of the literature.

BACKGROUND: Major amputations are indicated for advanced tumors when limb-preservation techniques have been exhausted. Radical surgery can result in significant palliation and possible cure. METHODS: We identified 40 patients who underwent forequarter (FQ) or hindquarter (HQ) amputations between May 2000 and January 2011. Patient demographics, tumor-related factors, and outcomes were reviewed. RESULTS: There were 30 FQ and 10 HQ amputations. The most common diagnoses were sarcoma (55%) and squamous cell carcinoma (25%). Patients presented with primary tumors (35%), regional recurrence (57.5%), or unresectable limb metastatic disease (7.5%). Presenting symptoms included fungating wounds (35%), intractable pain (78%), and limb dysfunction (65%). Operations were performed with curative intent (10%), curative/palliative intent (70%), or palliation alone (20%). Wound complications occurred in 35%. Pain was improved in 78% of patients following surgery. Despite a 91% negative margin rate, 79% of patients recurred either locally or distantly. Median overall survival was 10.9, 13.2, and 3.4 months in the curative, curative/palliative, and palliative groups, respectively. CONCLUSIONS: In the absence of conservative options, major amputations are indicated for the management of advanced tumors. These operations can be performed safely, resulting in effective palliation of debilitating symptoms. While recurrence rates remain high, some patients can achieve prolonged survival.

What are estimated reimbursements for lower extremity prostheses capable of surgical and nonsurgical lengthening?

BACKGROUND: Growing prostheses accommodate skeletally immature patients with bone tumors undergoing limb-preserving surgery. Early devices required surgical procedures for lengthening; recent devices lengthen without surgery. Expenses for newer expandable devices that lengthen without surgery are more than for their predecessors but overall reimbursement amounts are not known. QUESTIONS/PURPOSES: We sought to determine reimbursement amounts associated with lengthening of growing prostheses requiring surgical and nonsurgical lengthening. METHODS: We retrospectively reviewed 17 patients with growing prostheses requiring surgical expansion and eight patients with prostheses capable of nonsurgical expansion. Insurance documents were reviewed to determine the reimbursement for implantation, lengthening, and complications. Growth data were obtained from the literature. RESULTS: Mean reimbursement amounts of surgical and nonsurgical lengthenings were $9950 and $272, respectively. Estimated reimbursements associated with implantation of a growing prosthesis varied depending on age, sex, and location. The largest difference was found for 4-year-old boys with distal femoral replacement where reimbursement for expansion to maturity for surgical and nonsurgical lengthening prostheses would be $379,000 and $208,000, respectively. For children requiring more than one surgical expansion, net reimbursements were lower when a noninvasive lengthening device was used. Annual per-prosthesis maintenance reimbursements to address complications for surgical and nonsurgical lengthening prostheses were $3386 and $1856, respectively. CONCLUSIONS: This study showed that reimbursements for lengthening of growing endoprostheses capable of nonsurgical expansion may be less expensive in younger patients, particularly male patients undergoing distal femur replacement, than endoprostheses requiring surgical lengthening. Longer outcomes studies are required to see if reimbursements for complications differ between devices. LEVEL OF EVIDENCE: Level III, economic and decision analysis. See the Guidelines for Authors for a complete description of levels of evidence.

Poor survival for osteosarcoma of the pelvis: a report from the Children's Oncology Group.

BACKGROUND: The pelvis is an infrequent site of osteosarcoma and treatment requires surgery plus systemic chemotherapy. Poor survival has been reported, but has not been confirmed previously by the Children's Oncology Group (COG). In addition, survival of patients with pelvic osteosarcomas has not been compared directly with that of patients with nonpelvic disease treated on the same clinical trials. QUESTIONS/PURPOSES: First, we assessed the event-free (EFS) and overall survival (OS) of patients with pelvic osteosarcoma treated on COG clinical trials. We then asked whether patient survival compared with that of patients treated on the same clinical trials with nonpelvic disease. Finally, we asked whether patients with metastatic disease at initial diagnosis had worse survival. METHODS: We retrospectively reviewed data from 1054 patients with osteosarcoma treated in four studies between 1993 and 2005. Twenty-six of the 1054 patients (2.5%) had a primary tumor of the pelvis. At diagnosis, nine patients had metastatic disease. The minimum followup was 2 months (mean, 34 months; range, 2-102 months). RESULTS: Two of the nine patients with metastatic disease at diagnosis and five of the 17 with localized disease were alive at last contact. Estimates of the 5-year EFS for localized versus metastatic disease of the pelvis were 22% versus 23%. OS for patients with localized versus metastatic disease was 47% versus 22%. Patients with osteosarcoma in all other locations had a 5-year EFS of 57% and OS of 69%. CONCLUSIONS: Our analysis confirms poor survival for patients with pelvic osteosarcoma. Survival with metastatic disease in the absence of a pelvic primary tumor is similar to that for localized or metastatic pelvic osteosarcoma. Improved surgical or medical therapy is needed, and patients with pelvic osteosarcoma may warrant alternate or experimental therapy.

Outcomes and Complications of Pelvic Chondrosarcomas Treated Using Navigation Guidance and Multidisciplinary Approach: Is the Tumor Volume a Prognostic Factor?

(1) Background: Pelvic Chondrosarcomas (CS) have a poor prognosis. The grade is the most important survival predictor; other factors are periacetabular location and Dedifferentiated CS subtype. The aim of the study is to investigate a series of CS of the pelvis, to analyze the prognostic factors that affect outcomes and to demonstrate how the use of intraoperative navigation can reduce the complications without worse outcomes. (2) Methods: Retrospective study on 35 patients (21 M, 14 F), median age at surgery 54 years (IQR 41−65), with pelvic CS, treated with hemipelvectomy under navigation guidance. (3) Results: 30 high-grade CS and 5 low-grade CS; mean follow-up 51.4 months. There was a positive linear correlation between the tumor volume and the presence of local recurrence at follow-up. The mean survival time of patients with larger chondrosarcoma volume was lower, but not significantly so. Lower MSTS score was associated with significantly lower survival time (p < 0.001). (4) Conclusion: in this series overall survival, LR and distant metastasis were comparable with recent literature, while complication rate was lower compared to similar series without the use of navigation. There was a correlation between tumor volume and local recurrence rate but not with the presence of metastasis at follow up.

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.

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.

Enhancing soft tissue ingrowth in proximal femoral arthroplasty with aortograft sleeve: a novel technique and early results.

Hip abductor function is critical to joint stability after proximal femoral arthroplasty. Normal soft tissue relationships are often violated during this procedure for complete tumor resection. Abductor insufficiency leads to abnormal gait mechanics and poor function. To improve soft tissue stability about a metallic proximal femoral endoprosthesis, we devised a novel use of vascular graft material. Two patients received a proximal femoral arthroplasty using this technique. These patients were followed for an average of 26.5 months. They demonstrated mean active hip abduction of 48°, hip flexion of 90°, mean Musculoskeletal Tumor Society score of 24 (80%), and Toronto Extremity Salvage Score of 80. We believe that this technique may be useful in achieving soft tissue stability about a metal endoprosthesis and may facilitate better function in patients undergoing this surgery.

Osteosarcoma: An Evolving Understanding of a Complex Disease.

Osteosarcoma is the most common primary bone sarcoma and affects both children and adults. The cornerstone of treatment for patients with localized and oligometastatic disease remains neoadjuvant chemotherapy, surgical resection of all sites of disease, followed by adjuvant chemotherapy. This approach is associated with up to an 80% 5-year survival. However, survival of patients with metastatic disease remains poor, and overall, osteosarcoma remains a challenging disease to treat. Advances in the understanding of molecular drivers of the disease, identification of poor prognostic factors, development of risk-stratified treatment protocols, successful completion of large collaborative trials, and surgical advances have laid the ground work for progress. Advances in computer navigation, implant design, and surgical techniques have allowed surgeons to improve patients' physical functional without sacrificing oncologic outcomes. Future goals include identifying effective risk stratification algorithms which minimize patient toxicity while maximizing oncologic outcomes and continuing to improve the durability, function, and patient acceptance of oncologic reconstructions.

Malignancy in giant cell tumor of bone in the extremities.

BACKGROUND: Malignancy in giant cell tumor of bone (GCTB) is a rare tumor with relevant literature being sparse. In primary malignant GCTB, distinct areas of benign GCTB are juxtaposed with high-grade sarcoma, while in secondary malignant GCTB sarcoma occurs at the site of previously managed GCTB. This study assesses the distinguishing characteristics of patients with this condition, the time interval for development of secondary malignant GCTB, the outcome of treatment, and explores factors associated with oncologic outcomes. METHODS: This is a retrospective case series of patients from a prospectively collected institutional musculoskeletal oncology database. From January 1998 to December 2016, 1365 patients were managed for extremity GCTBs. 32 (2.3%) patients had malignant GCTB, including 12 with primary malignant GCTB and 20 with secondary malignant GCTB. The study population comprised 18 males and 14 females presenting at a mean age of 33.7 years (±13.0) and followed for a mean of 9.5 years (±7.4). Data were collected on patient and treatment-related factors, and the occurrence of local recurrence, metastasis, and death. The time from the diagnosis of GCTB to the secondary malignant GCTB was defined as the latent period. RESULTS: Malignant GCTB most commonly presents in the distal femur and proximal tibia with pain and swelling. Radiologically, they are aggressive Campanacci Grade III tumors with prominent bony destruction and soft tissue extension. In the 20 patients with secondary malignant GCTB, the tumors were osteosarcoma in 15, undifferentiated pleomorphic sarcoma in 4 patients and fibrosarcoma in one patient. The mean latent period in patients with secondary malignant GCTB was 7.9 year (±7.3). The median recurrence-free survival (RFS) of secondary malignant GCTB (latent period) and benign GCTB were 61.5 and 19 months respectively (p < 0.001), receiver operating curve analysis found 49.5 months to be the critical threshold, with a longer interval to recurrence being seen in malignant recurrence. The 5 and 10-year overall survival rate of malignant GCTB were 45.8% and 36.1% respectively. The 5-year survival rates of primary malignant GCTB and secondary malignant GCTB were 56.2% and 40.0% respectively (p = 0.188). Adequate surgical margins decreased the local recurrence (LR) rate (P = 0.006). Pulmonary metastasis developed in 69% of patients. The median distant metastasis-free survival between malignant GCTB and benign GCTB were 9 and 21 months (p = 0.002). Chemotherapy was associated with a longer pulmonary metastasis free survival (13 months Vs 6 months, P = 0.002), but not with increased overall survival (57.0% Vs 33.3%, P = 0.167). CONCLUSIONS: Malignant GCTB carries a poor prognosis. Accurate diagnosis is critical to avoid inadequate surgical margins when treating primary malignant GCTB. Aggressive tumors and pulmonary metastasis should raise suspicion for malignant GCTB. Secondary malignant transformation should be suspected in patients presenting with recurrence especially after 4 years. Adjuvant chemotherapy use did not benefit survival, but was associated with increased pulmonary progression-free survival.

Budget Impact of Adaptive Abiraterone Therapy for Castration-Resistant Prostate Cancer.

BACKGROUND: The use of a novel strategy known as adaptive abiraterone therapy based on mathematical modeling of evolutionary dynamics of tumor subpopulations was shown in a clinical trial to extend the time to disease progression in patients with metastatic castration-resistant prostate cancer (CRPC) and reduced the use of abiraterone therapy. Although the clinical impact of adaptive abiraterone treatment is clear, the economic impact of this strategy has not been investigated. OBJECTIVE: To compare the cost of care with adaptive abiraterone therapy versus standard continuous abiraterone therapy in patients with metastatic CRPC, using patient billing data. METHODS: We performed a retrospective review of billing data for patients with metastatic CRPC who received abiraterone treatment at a large cancer center between June 1, 2012, and August 31, 2018. Patients were divided into 2 groups based on whether they received adaptive abiraterone therapy (N = 15) or continuous abiraterone therapy (N = 21). All patients with refractory, metastatic prostate cancer after castration that was indicated for abiraterone therapy were eligible for this study. Each patient in the adaptive abiraterone therapy cohort received abiraterone plus prednisone treatment until the patient reached a target threshold of 50% or more reduction in prostate-specific antigen (PSA) level compared with his PSA level before abiraterone therapy; treatment was then suspended until the PSA level rose above the 50% of PSA before abiraterone therapy target threshold. The continuous therapy cohort received abiraterone plus prednisone daily until radiographic progression. The primary outcomes were the mean annual cost of care per patient, including and excluding the cost of abiraterone, and the cost of care, by clinical category. RESULTS: The median time to disease progression was 25.8 months for patients who received adaptive abiraterone therapy compared with 12.1 months for patients who received continuous abiraterone therapy. Overall, the mean total, including the cost of drug, annual cost per patient who received adaptive abiraterone therapy was $79,093 compared with $146,782 for patients who received continuous abiraterone therapy (P <.0001). The annual cost of care per patient, excluding the cost of abiraterone, was $13,883 for those who received adaptive therapy versus $22,322 for those who received continuous abiraterone therapy (P = .2757), which was not statistically significant. CONCLUSION: Practical precision medicine strategies, such as adaptive abiraterone treatment or pharmacogenomics-targeted dosing, can use known biomarkers, such as PSA, to tailor therapy, generate improved outcomes, and reduce costs without the need for novel drug and diagnostic discovery and development. The results of this study suggest that a large clinical study of adaptive abiraterone therapy is warranted to validate the potential of this strategy to extend the time to disease progression and reduce costs of treatment of metastatic CRPC.