Can Periprosthetic Joint Infection of Tumor Prostheses Be Controlled With Debridement, Antibiotics, and Implant Retention?

BACKGROUND: Two-stage revision for periprosthetic joint infection (PJI) in patients who have undergone segmental replacement of the distal femur or proximal tibia after tumor resection can be associated with considerable morbidity, pain, and risk of complications because the procedure often results in removal of long, well-fixed stems from the diaphysis. A less-aggressive surgical approach, such as debridement, antibiotics, and implant retention (DAIR), may be attractive to patients and surgeons because of less morbidity, but the likelihood of eradicating infection in comparison to the traditional two-stage revision is not well established for oncology patients. Furthermore, the relative risk of subsequent amputation for DAIR versus two-stage revision has not been defined for this population. QUESTIONS/PURPOSES: (1) How does DAIR compare with two-stage revision in terms of infection control for patients with distal femoral or proximal tibial segmental modular endoprostheses? (2) Is DAIR as an initial procedure associated with an increased risk of amputation compared with two-stage revision for infection? METHODS: From the longitudinally maintained orthopaedic oncology surgical database at our institution, we identified 69 patients who had been treated for a clinical diagnosis of PJI at the knee between 1993 and 2015. We excluded 32% (22) of patients who did not meet at least one of the major criteria of the Musculoskeletal Infection Society (MSIS) for PJI, 3% (2) of patients who underwent immediate amputation, 3% (2) of patients who had a follow-up time of < 24 months, and 7% (5) of patients who did not have a primary tumor of the distal femur or proximal tibia. The study consisted of 38 patients, of whom eight underwent two-stage revision, 26 underwent DAIR, and four underwent extended DAIR (removal of all segmental components but with retention of stems and components fixed in bone) for their initial surgical procedure. To be considered free of infection, patients had to meet MSIS standards, including no positive cultures, drainage, or surgical debridement for a minimum of 2 years from the last operation. Factors associated with time-dependent risk of infection relapse, clearance, amputation, and patient survival were analyzed using Kaplan-Meier survivorship curves and the log-rank test to compare factors. Association of demographic and treatment factors was assessed using chi-square and Fisher exact tests. RESULTS: Continuous infection-free survival at 5 years was 16% (95% CI 2% to 29%) for patients undergoing DAIR compared with 75% (95% CI 45% to 100%) for patients undergoing two-stage revision (p = 0.006). The median (range) number of total surgical procedures was 3 per patient (1 to 10) for DAIR and 2 (2 to 5) for two-stage revision. Twenty-nine percent (11 of 38) of patients eventually underwent amputation. Survival without amputation was 69% (95% CI 51% to 86%) for DAIR compared with 88% (95% CI 65% to 100%) for two-stage revision at 5 years (p = 0.34). The cumulative proportion of patients achieving infection-free status (> 2 years continuously after last treatment) and limb preservation was 58% (95% CI 36% to 80%) for patients initially treated with DAIR versus 87% (95% CI 65% to 100%) for patients first treated with two-stage revision (p = 0.001). CONCLUSION: Infection control was better with two-stage revision than DAIR. The chance of eventual clearance of infection with limb preservation was better when two-stage revision was chosen as the initial treatment. However, the loss to follow-up in the two-stage revision group would likely make the true proportion of infection control lower than our estimate. Our experience would suggest that the process of infection eradication is a complex and difficult one. Most patients undergo multiple operations. Nearly one-third of patients eventually underwent amputation, and this was a serious risk for both groups. While we cannot strongly recommend one approach over the other based on our data, we would still consider the use of DAIR in patients who present with acute short duration of symptoms (< 3 weeks), no radiographic signs of erosion around fixed implants, and organisms other than Staphylococcus aureus. We would advocate the extended DAIR procedure with removal of all segmental or modular components, and we would caution patients that there is a high likelihood of needing further surgery. A prospective trial with strict adherence to indications may be needed to evaluate the relative merits of an extended DAIR procedure versus a two-stage revision. LEVEL OF EVIDENCE: Level III, therapeutic study.

Reconstruction of Bony Defects With Motorized Intramedullary Nails After Tumor Resection.

Motorized intramedullary lengthening nails allow for transport of a bone segment for limb lengthening, deformity correction, healing of nonunion, and intercalary distraction osteogenesis. Resection of tumors involving the bone can result in substantial defects that require reconstruction. Use of these nails allows for a biologic reconstruction with the incorporation of allograft or by distraction osteogenesis. Limb lengthening after an internal hemipelvectomy where the hip joint is resected can be performed to improve gait, decrease pain, and prevent the need for a custom shoe or shoe lift. Using these nails in compression aids the incorporation of intercalary allografts and prevents stress shielding and stress risers within the graft when compared with plating. It also allows for a subsequent lengthening of the limb using the same implant. Plate-assisted bone segment transport or the use of a bone transport nail allows for a true biologic reconstruction of an intercalary defect using distraction osteogenesis. These implants provide the orthopaedic oncologist with more options for reconstruction and the potential to improve the function and outcomes of their patients.

Practice Pattern Variability in the Management of Regional Lymph Node Metastasis in Extremity and Trunk Soft Tissue Sarcoma: A Survey of the Society of Surgical Oncology and Musculoskeletal Tumor Society Membership.

BACKGROUND: Regional lymph node metastasis in extremity and trunk soft tissue sarcoma (ETSTS) is rare with no standardized management. We sought to determine management patterns for regional lymph node metastasis in ETSTS. METHODS: A survey regarding the management of ETSTS lymph node metastasis was distributed to the membership of the Musculoskeletal Tumor Society (MSTS) and the Society of Surgical Oncology (SSO) in January 2022. The survey queried the type of training (surgical oncology, orthopedic oncology), details of their practice setting, and management decisions of hypothetical ETSTS scenarios that involved potential or confirmed lymph node metastasis. RESULTS: The survey was distributed to 349 MSTS members (open rate of 63%, completion rate 21%) and 3026 SSO members (open rate of 55%, completion rate 4.7%) and was completed by 214 respondents, of whom 73 (34.1%) and 141 (65.9%) were orthopedic oncology and surgical oncology fellowship-trained, respectively. The majority of respondents practiced in an academic setting (n = 171, 79.9%) and treat >10 extremity sarcoma cases annually (n = 138, 62.2%). In scenarios with confirmed nodal disease for clear cell and epithelioid sarcoma, surgical oncologists were inclined to perform lymphadenectomy, while orthopedic oncologists were inclined to offer targeted lymph node excision with adjuvant radiation (p < 0.001). There was heterogeneity of responses regarding the management of nodal disease regardless of training background. CONCLUSION: Self-reported management of nodal disease in ETSTS was variable among respondent groups with differences and similarities based on training background. These data highlight the variability of practice for nodal disease management and the need for consensus-based guidelines.

What Is the Prosthetic Survival After Resection and Intercalary Endoprosthetic Reconstruction for Diaphyseal Bone Metastases of the Humerus and Femur?

BACKGROUND: Large metastatic lesions of the diaphysis can cause considerable pain and result in difficult surgical challenges. Resection and cemented intercalary endoprosthetic reconstruction offer one solution to the problem, but it is an extensive operation that might not be tolerated well by a debilitated patient. The risk of aseptic loosening and revision after intercalary endoprosthetic replacement has varied in previous reports, which have not examined the risk of revision in the context of patient survival. QUESTIONS/PURPOSES: (1) In a small case series from one institution, what is the survivorship of patients after cemented intercalary endoprosthetic replacement for diaphyseal metastasis, and what is the cumulative incidence of revision for any reason? (2) What are the complications associated with cemented intercalary reconstruction? (3) What is the functional outcome after the procedure as assessed by the MSTS93 score? METHODS: We retrospectively studied 19 patients with diaphyseal long bone metastases who were treated with resection and cemented intercalary endoprosthetic reconstruction by five participating surgeons at one referral center from 2006 to 2017. There were 11 men and eight women with a median age of 59 years (range 46 to 80 years). The minimum follow-up required for this series was 12 months; however, patients who reached an endpoint (death, radiographic loosening, or implant revision) before that time were included. One of these 19 patients was lost to follow-up but was not known to have died. The median follow-up was 24 months (range 0 to 116 months). Eight of the 19 patients presented with pathologic fractures. Ten of 19 lesions involved the femur, and nine of 19 were in the humerus. The most common pathologic finding was renal cell carcinoma (in 10 of 19). Survival estimates of the patients were calculated using the Kaplan-Meier method. A competing risks estimator was used to evaluate implant survival, using death of the patient as the competing risk. We also estimated the cumulative incidence of aseptic loosening in a competing risk analysis. Radiographs were analyzed for radiolucency at the bone-cement-implant interfaces, fracture, integrity of the cement mantle, and component position stability. Complications were assessed using record review that was performed by an individual who was not involved in the initial care of the patients. Functional outcomes were assessed using the MSTS93 scoring system. RESULTS: Patient survivorship was 68% (95% CI 50% to 93%) at 1 year, 53% (95% CI 34% to 81%) at 2 years, and 14% (95% CI 4% to 49%) at 5 years; the median patient survival time after reconstruction was 25 months (range 0 to 116 months). In the competing risk analysis, using death as the competing risk, the cumulative incidence of implant revision was 11% (95% CI 2% to 29%) at 1 year and 16% (95% CI 4% to 36%) at 5 years after surgery; however, the cumulative incidence of aseptic loosening (with death as a competing risk) was 22% (95% CI 6% to 43%) at 1 year and 33% (95% CI 13% to 55%) at 5 years after surgery. Other complications included one patient who died postoperatively of cardiac arrest, one patient with delayed wound healing, two patients with bone recurrence, and one patient who experienced local soft tissue recurrence that was excised without implant revision. Total MSTS93 scores improved from a mean of 12.6 ± 8.1 (42% ± 27%) preoperatively to 21.5 ± 5.0 (72% ± 17%) at 3 months postoperatively (p < 0.001) and 21.6 ± 8.5 (72% ± 28%) at 2 years postoperatively (p = 0.98; 3 months versus 2 years). CONCLUSION: Resection of diaphyseal metastases with intercalary reconstruction can provide stability and short-term improvement in function for patients with advanced metastatic disease and extensive cortical destruction. Aseptic loosening is a concern, particularly in the humerus; however, the competing risk analysis suggests the procedure is adequate for most patients, because many in this series died of disease without undergoing revision. LEVEL OF EVIDENCE: Level IV, therapeutic study .

Hypofractionated, 3-week, preoperative radiotherapy for patients with soft tissue sarcomas (HYPORT-STS): a single-centre, open-label, single-arm, phase 2 trial.

BACKGROUND: The standard preoperative radiotherapy regimen of 50 Gy delivered in 25 fractions for 5 weeks for soft tissue sarcomas results in excellent local control, with major wound complications occurring in approximately 35% of patients. We aimed to investigate the safety of a moderately hypofractionated, shorter regimen of radiotherapy, which could be more convenient for patients. METHODS: This single-centre, open-label, single-arm, phase 2 trial (HYPORT-STS) was done at a single tertiary cancer care centre (MD Anderson Cancer Center, Houston, TX, USA). We administered preoperative radiotherapy to a dose of 42·75 Gy in 15 fractions of 2·85 Gy/day for 3 weeks (five fractions per week) to adults (aged ≥18 years) with non-metastatic soft tissue sarcomas of the extremities or superficial trunk and an Eastern Cooperative Oncology Group performance status of 0-3. The primary endpoint was a major wound complication occurring within 120 days of surgery. Major wound complications were defined as those requiring a secondary operation, or operations, under general or regional anaesthesia for wound treatment; readmission to the hospital for wound care; invasive procedures for wound care; deep wound packing to an area of wound measuring at least 2 cm in length; prolonged dressing changes; repeat surgery for revision of a split thickness skin graft; or wet dressings for longer than 4 weeks. We analysed our primary outcome and safety in all patients who enrolled. We monitored safety using a Bayesian, one-arm, time-to-event stopping rule simulator comparing the rate of major wound complications at 120 days post-surgery among study participants with the historical rate of 35%. This trial is registered with ClinicalTrials.gov, NCT03819985, recruitment is complete, and follow-up continues. FINDINGS: Between Dec 18, 2018, and Jan 6, 2021, we assessed 157 patients for eligibility, of whom 120 were enrolled and received hypofractionated preoperative radiotherapy. At no time did the stopping rule computation indicate that the trial should be stopped early for lack of safety. Median postoperative follow-up was 24 months (IQR 17-30). Of 120 patients, 37 (31%, 95% CI 24-40) developed a major wound complication at a median time of 37 days (IQR 25-59) after surgery. No patient had acute radiation toxicity (during radiotherapy or within 4 weeks of the radiotherapy end date) of grade 3 or worse (Common Terminology Criteria for Adverse Events [CTCAE] version 4.0) or an on-treatment serious adverse event. Four (3%) of 115 patients had late radiation toxicity (≥6 months post-surgery) of at least grade 3 (CTCAE or Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer Late Radiation Morbidity Scoring Scheme): femur fractures (n=2), lymphoedema (n=1), and skin ulceration (n=1). There were no treatment-related deaths. INTERPRETATION: Moderately hypofractionated preoperative radiotherapy delivered to patients with soft tissue sarcomas was safe and could therefore be a more convenient alternative to conventionally fractionated radiotherapy. Patients can be counselled about these results and potentially offered this regimen, particularly if it facilitates care at a sarcoma specialty centre. Results on long-term oncological, late toxicity, and functional outcomes are awaited. FUNDING: The National Cancer Institute.

Certain risk factors for patients with desmoid tumors warrant reconsideration of local therapy strategies.

BACKGROUND: The objective of this study was to evaluate treatment outcomes for patients with desmoid tumors (DTs) receiving local therapy with surgery alone, radiation therapy (RT) alone, or combined modality therapy (RT and surgery). METHODS: This was a cross-sectional cohort study of 412 patients with nonmesenteric DTs who received local therapy at the authors' institution between 1965 and 2018. RESULTS: The median follow-up time was 95 months (range, 1-509 months). Local recurrence occurred in 127 patients (31%) at a median time of 21 months (interquartile range, 12-38 months). The 5-year local control (LC) rate was 67%. Patient or tumor factors that were significantly associated with poorer 5-year LC in a multivariable analysis included an age ≤ 30 years (57% vs 75% for an age > 30 years; hazard ratio [HR], 1.73; P = .004), an extremity location (57% vs 71% for a nonextremity location; HR, 1.77; P = .004), and large tumors (59% for >10 cm [HR, 2.17; P = .004] and 65% for 5.1-10 cm [HR, 1.71; P = .02] vs 76% for ≤5 cm). Subset analyses of these high-risk patients revealed no local therapy strategy to be superior for young patients ≤ 30 years old (HR for surgery, 1.42; P = .33; HR for RT, 1.36; P = .38) or for large tumors > 10 cm (HR for surgery, 1.55; P = .46; HR for RT, 0.91; P = .91). However, for patients with extremity tumors, surgery alone was significantly associated with inferior LC (HR for surgery, 5.15; P < .001; HR for RT, 1.51; P = .38). CONCLUSIONS: Local therapy provides durable tumor control in the majority of patients with DTs. However, young patients, patients with an extremity location, and patients with large tumors are at increased risk of recurrence. When active treatment is indicated, systemic therapy should perhaps be considered as a first-line option in these high-risk subsets. Prospective multi-institutional studies evaluating this strategy are warranted.

BMTP-11 is active in preclinical models of human osteosarcoma and a candidate targeted drug for clinical translation.

Osteosarcoma occurs predominantly in children and young adults. High-grade tumors require multidisciplinary treatment consisting of chemotherapy in the neoadjuvant and adjuvant settings, along with surgical intervention. Despite this approach, death from respiratory failure secondary to the development and progression of pulmonary metastases remains a significant problem. Here, we identify the IL-11 receptor α subunit (IL-11Rα) as a cell surface marker of tumor progression that correlates with poor prognosis in patients with osteosarcoma. We also show that both IL-11Rα and its ligand, IL-11, are specifically up-regulated in human metastatic osteosarcoma cell lines; engagement of this autocrine loop leads to tumor cell proliferation, invasion, and anchorage-independent growth in vitro. Consistently, IL-11Rα promotes lung colonization by human metastatic osteosarcoma cells in vivo in an orthotopic mouse model. Finally, we evaluate the IL-11Rα-targeted proapoptotic agent bone metastasis-targeting peptidomimetic (BMTP-11) in preclinical models of primary intratibial osteosarcomas, observing marked inhibition of both tumor growth and lung metastases. This effect was enhanced when BMTP-11 was combined with the chemotherapeutic drug gemcitabine. Our combined data support the development of approaches targeting IL-11Rα, and establish BMTP-11 as a leading drug candidate for clinical translation in patients with high-risk osteosarcoma.

Local recurrence of Ewing sarcoma: Is wide excision an acceptable treatment?

BACKGROUND AND OBJECTIVES: Local recurrence in Ewing sarcoma (ES) is associated with poor prognosis. The purpose of the study is to determine what factors affect overall survival after local recurrence and whether wide excision constitutes appropriate treatment. METHODS: From 1992 to 2017, 26 patients were treated for local recurrence of ES. Sixteen patients presented with local recurrence only while 10 had metastasis. The median follow-up was 23 months (range, 3-255 months). Overall survival was assessed with Kaplan-Meier analysis. RESULTS: At the last follow-up, seven of 26 (27%) patients were alive. Overall survival after local recurrence was 28% at 5 years. Later onset of local recurrence (P = .041), surgical treatment (P < .001), and complete eradication of all recurrent disease (P < .001) predicted better survival. Metastasis was associated with worse survival (P = .014). All three patients who survived more than 10 years were treated with wide local excision. A second local recurrence developed in seven patients (28%) but did not predict worse overall survival. CONCLUSIONS: Overall survival after local recurrence is better for patients with nonmetastatic disease treated surgically. Wide excision can be compatible with long survival. We do not advocate amputation on a routine basis for local recurrence. Complete eradication of all diseases is associated with better survival.

Do Early Results of Proximal Humeral Allograft-Prosthetic Composite Reconstructions Persist at 5-year Followup?

BACKGROUND: Insufficiency of the rotator cuff is a major problem after resections of proximal humeral tumors and can limit shoulder motion despite preservation of the deltoid muscle and axillary nerve. Allograft-prosthetic composite reconstruction offers one method to reattach the rotator cuff tendons and has been successful in small studies with short followup. However, data are lacking with regard to implant durability, changes in Musculoskeletal Tumor Society (MSTS) scores over time, and delayed complications with extended followup. QUESTIONS/PURPOSES: (1) What is the cumulative incidence of allograft-prosthetic composite revision surgery 5 years after the procedure? (2) What are the early- and intermediate-term MSTS scores of allograft-prosthetic composite reconstruction of the shoulder? (3) What are the complications of allograft-prosthetic composite reconstruction? METHODS: Twenty-one patients underwent allograft-prosthetic composite reconstruction after tumor resection of the proximal humerus between 2000 and 2015. Six patients who were lost to followup were not included. All patients had malignant or aggressive benign tumors that could be treated with a wide intraarticular approach preserving the deltoid muscle, axillary nerve, and glenoid. Cumulative incidence of implant revision was calculated with death of the patient as a competing risk. Minimum followup was 24 months (with the exception of one patient who died at 22 months), and median followup was 97 months (range, 20-198 months). The upper extremity MSTS score was used to assess function. Various complications were identified from radiographs and charts. RESULTS: The cumulative risk of implant revision was 10.1% at 5 years (95% confidence interval [CI], 1.6%-28.0%). Mean MSTS scores were 86% (± SD 9%) at 1 year and 78% (± SD 13%) at 5 years (mean difference ± SD 9% ± 14%, p = 0.015). Mean active forward elevation was 101° (± SD 33°) at 1 year and 92° (± SD 34°) at 5 years (mean difference ± SD 8° ± 36°, p = 0.41). Notable adverse events included progressive radiographic superior subluxation > 1 cm after 12 months followup (12 of 21 patients), delayed union > 12 months (10 of 21 patients), resorption of the greater tuberosity (nine of 21 patients), and aseptic loosening (three of 21 patients). CONCLUSIONS: At intermediate 5-year followup, allograft-prosthetic composite reconstruction of the proximal humerus has an acceptable overall MSTS score and a low incidence of implant revision, but loss of patients to followup and exclusion from the study likely make the results seem better than they actually are. The MSTS score deteriorates between 1 and 5 years. Decreased active forward elevation is not likely to be the sole reason for worsening MSTS scores. A variety of delayed complications including delayed union, resorption of the greater tuberosity, and superior subluxation occurs frequently and may contribute to overall scores. Future studies that compare allograft-prosthetic composites against other forms of reconstruction should attempt to control for possible selection bias and have sufficiently long followup to detect the deterioration of MSTS scores that occur with time. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Phase II study of neoadjuvant checkpoint blockade in patients with surgically resectable undifferentiated pleomorphic sarcoma and dedifferentiated liposarcoma.

BACKGROUND: Soft tissue sarcomas are a heterogeneous and rare group of solid tumors of mesenchymal origin that can arise anywhere in the body. Although surgical resection is the mainstay of treatment for patients with localized disease, disease recurrence is common and 5-year overall survival is poor (~ 65%). Both radiation therapy and conventional chemotherapy are used to reduce local and distant recurrence. However, the utility of radiation therapy is often limited by disease location (in the case of retroperitoneal sarcomas, for instance) while systemic therapy with conventional lines of chemotherapy offer limited efficacy and are often poorly tolerated and associated with significant toxicity. Within the past decade, major advances have been made in the treatment of other malignancies including melanoma, renal cell carcinoma, and non-small cell lung carcinoma with the advent of immune-checkpoint inhibitors such as ipilimumab (anti-CTLA4), pembrolizumab (anti-PD1), and nivolumab (anti-PD1). The recently published SARC028 (NCT02301039), an open label, phase II, multicenter trial of pembrolizumab in patients with advanced bone and soft tissue sarcomas reported promising activity in select histologic subtypes of advanced STS, including undifferentiated pleomorphic sarcoma and dedifferentiated liposarcoma. METHODS: There is a clear need for novel and effective adjuncts in the treatment of STS. We hypothesize that immune checkpoint blockade will be effective in patients with surgically resectable primary or locally recurrent dedifferentiated liposarcoma and undifferentiated pleomorphic sarcoma when administered in the neoadjuvant setting. The primary aim of this phase II, single-center, open label, randomized non-comparative trial is to determine the pathologic response to neoadjuvant nivolumab monotherapy and combination nivolumab/ipilimumab in patients with resectable dedifferentiated liposarcoma of the retroperitoneum or undifferentiated pleomorphic sarcoma of the trunk or extremity treated with concurrent standard of care neoadjuvant radiation therapy. DISCUSSION: This study will help define the role of single agent anti-PD1 and combination anti-CTLA4 and anti-PD1 therapy in patients with surgically resectable dedifferentiated liposarcoma and undifferentiated pleomorphic sarcoma. TRIAL REGISTRATION: ClinicalTrials.gov NCT03307616 , registered October 12, 2017.

Is a Cephalomedullary Nail Durable Treatment for Patients With Metastatic Peritrochanteric Disease?

BACKGROUND: Although cephalomedullary nail fixation is often used for metastatic peritrochanteric lesions of the femur, there is concern regarding the durability of the implant in comparison to endoprosthetic reconstruction. Previous studies have reported the proportion of patients who undergo reoperation for loss of stability, but the adequacy of the construct has not been critically evaluated in a competing risk analysis that incorporates death of the patient in the calculation. QUESTIONS/PURPOSES: (1) What is the cumulative incidence of reoperation of cephalomedullary nails with death as a competing risk for metastatic lesions of the proximal femur? (2) What is the survival of patients with metastases to the proximal femur after cephalomedullary nailing? (3) What clinical factors are associated with implant stability in these patients? METHODS: Between 1990 and 2009, 11 surgeons at one center treated 217 patients with cephalomedullary nails for metastatic proximal femoral lesions. This represented 40% (217 of 544) of the patients undergoing surgery for metastases in this location during the study period. In general, we used cephalomedullary nails when there was normal bone in the femoral head, no fracture in the neck, and a moderate-sized lesion; we favored bipolar hemiarthroplasty for femoral neck fractures and disease affecting the femoral head; finally, we used proximal femoral endoprosthetic replacement for large lesions with severe bone destruction. A retrospective study was conducted of 199 patients with cephalomedullary nails for peritrochanteric metastases from 1990 to 2009. Pathologic fracture, defined as a breach in cortex with a clear fracture line either with or without displacement, was present in 61 patients. The most common primary cancers were breast (42 of 199 patients [21%]), lung (37 of 199 patients [18%]), and renal cell (34 of 199 patients [17%]). A competing risk analysis was performed to describe the cumulative incidence of implant revision. Patient overall survival was assessed by Kaplan-Meier survivorship. A univariate analysis was performed to determine whether there was an association between revision surgery and various patient factors, including tumor histology, pathologic fracture, cementation, and radiation. RESULTS: Loss of implant stability necessitating revision surgery occurred in 19 of 199 patients (10%). In a competing risk analysis with death of the patient as the competing event, the cumulative incidence of revision surgery was 5% (95% confidence interval [CI], 3%-9%) at 12 months and 9% (95% CI, 5%-13%) at 5 years. Using Kaplan-Meier analysis, the overall patient survival was 31% (95% CI, 25%-37%) at 12 months and 5% (95% CI, 3%-9%) at 60 months. Patients with lung cancer had the shortest overall survival of 11% (95% CI, 1%-21%) at 12 months, and patients with multiple myeloma had the longest overall survival of 71% (95% CI, 49%-94%) at 12 months (p < 0.001). Duration of patient survival beyond the median 7 months was the only factor associated with a greater likelihood of revision surgery. Factors not associated with revision included tumor histology, pathologic fracture, closed versus open nailing, cementation, gender, age, and postoperative radiation. CONCLUSIONS: The competing risk analysis demonstrates a relatively low cumulative incidence of reoperation and suggests that cephalomedullary nailing is reasonable for patients with moderate-sized proximal femoral metastasis not affecting the femoral head. For the large majority of patients, the construct achieves the goal of stabilizing the femur for the duration of the patient's life. Longer patient survival was associated with greater risk of revision surgery, but no particular tumor histology was found to have a greater cumulative incidence of reoperation. Future work with a larger number of patients and stricter surgical indications may be needed to corroborate these findings. LEVEL OF EVIDENCE: Level III, therapeutic study.

Bone and Soft-Tissue Tumors for the General Orthopaedic Surgeon: Diagnosis, Management, and Avoiding Errors.

Orthopaedic surgeons will encounter a variety of bone and soft-tissue lesions throughout their careers. Although most of these lesions will be benign and nonaggressive, many others will require management that is time consuming, challenging, and stressful for surgeons and patients. Errors in management, if they occur, may delay diagnosis and hinder efforts to perform limb-sparing surgery. A systematic approach to the evaluation of adult and pediatric patients with bone or soft-tissue tumors will help general orthopaedic surgeons correctly diagnose and manage tumors, understand when to refer patients to an orthopaedic oncologist, and avoid management errors.

Ewing sarcoma family of tumors in children younger than 10 years of age.

AIM: Few data exist regarding the clinical characteristics and outcome of young children with Ewing sarcoma family of tumors (ESFT). METHODS: We reviewed the records of ESFT patients at our institution younger than 10 years of age at diagnosis. RESULTS: Forty-two patients were identified. Median age was 6.4 years (range 0.6-9.5 years). Most patients had T2 (>5 cm) tumors (n = 31; 74%). Most common primary site was the extremity (n = 17; 41%). Seven patients (17%) had metastasis at diagnosis. For local tumor control, 20 patients had surgery only, 13 had radiation therapy only, and 6 had surgery plus radiation. Surgical margin status was negative in 19 patients (73%). Median follow-up was 4.7 years (range 0.7-29.7 years), and 5-year relapse-free survival (RFS) and overall survival (OS) estimates were 67% (95% CI: 53-84%) and 82% (95% CI: 71-95%), respectively. Metastasis at presentation was the only significant predictor for decreased RFS (P = 0.008) and OS (P = 0.01). A trend was seen for T2 tumors with worse OS (P = 0.09). CONCLUSION: Patients younger than 10 years of age with ESFT may have a better OS than older patients, but further study of a homogeneously treated larger cohort is needed.

Is It Appropriate to Treat Sarcoma Metastases With Intramedullary Nailing?

BACKGROUND: Patients with primary bone and soft tissue sarcoma are at risk for skeletal metastases. Although uncommon, these metastases can result in impending or pathologic fractures. Intramedullary nailing traditionally has been an accepted form of palliative treatment for patients with metastatic carcinoma, but we could find no studies that report specifically on intramedullary nailing of metastatic sarcoma lesions. QUESTIONS/PURPOSES: We asked: (1) What is the survival of patients with an impending or pathologic fracture from a sarcoma metastasis? (2) What proportion of patients treated with intramedullary nailing subsequently underwent a revision procedure or nail removal during their lifetimes? METHODS: Between 1996 and 2014, we performed 40 intramedullary nailing procedures in 34 patients with multifocal metastases from sarcomas who showed signs or symptoms of impending fracture or who presented with a pathologic fracture. All of these patients are accounted for, either through the time of death or to the present, and all are included at a mean of 13 months (range, 0.3-86 months) in this retrospective study. During the study period, we generally applied the same surgical indications for patients with nailing of metastatic sarcoma lesions as we did for patients with metastatic carcinoma; in general, we used intramedullary nailing (with or without cement) rather than resection for diaphyseal lesions with less cortical destruction and no substantial soft tissue mass or metadiaphyseal lesions that could be adequately supplemented with cementation. The goal was to use this approach when it would allow immediate weightbearing, or in patients whose medical conditions were such that a more-extensive procedure seemed unsafe. During the same period, an additional 58 patients underwent resection procedures for metastatic sarcomas to long bones because they either did not meet the above indications, had a solitary resectable metastasis, or because of surgeon preference; these patients were excluded from this study. The median age of the patients was 52 years (range, 27-81 years). Eleven patients with 11 impending or pathologic fractures were documented to have received either preoperative or postoperative radiation therapy and 29 patients received some form of chemotherapy. RESULTS: Thirty (88%) patients died during the period of observation, at a median of 5 months (range, 0.3-80 months) after surgery. Twenty-nine patients (85%) underwent no additional surgery and retained their original intramedullary nail. One patient (3%) underwent nail removal for infection, and four patients (12%) underwent further surgical revision secondary to local progression. CONCLUSIONS: Patients with an impending or pathologic fracture from multifocal metastatic sarcoma to a long bone have a dismal prognosis, but they may gain short-term benefit from surgical fixation with the goal of reducing pain and maintaining mobility. Although we have no group for comparison, such as treating with radiotherapy alone or resection and an endoprosthesis, our findings suggest that use of intramedullary nails is helpful for providing fixation that in most instances lasts for the lifetime of patients with multifocal bone metastases from sarcomas. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Soft-Tissue Tumors: A Pictorial- and Case-Based Guide to Diagnosis and Management.

General orthopaedic surgeons must learn how to appropriately evaluate patients with soft-tissue masses who present at their office. Although the incidence of benign soft-tissue sarcomas substantially outnumbers that of malignant soft-tissue sarcomas, the mismanagement of soft-tissue tumors markedly increases a patient's morbidity. The appropriate use of imaging modalities helps general orthopaedic surgeons accurately diagnose a soft-tissue mass, initiate appropriate management of a soft-tissue mass, and gain a better understanding of which patients with soft-tissue lesions should be referred to an orthopaedic oncologist.

Optimization of Free-Flap Limb Salvage and Maximizing Function and Quality of Life Following Oncologic Resection: 12-Year Experience.

INTRODUCTION: A knowledge gap exists regarding factors to optimize limb salvage and function following oncologic resection. METHODS: We conducted a retrospective review of all free flaps performed for upper extremity (UE) and lower extremity (LE) salvage from 2000 to 2012. RESULTS: Overall, 220 patients underwent free-flap reconstruction for limb salvage (UE: 64, and LE: 156). Flaps were classified as muscle-only (n = 77), myocutaneous (MC; n = 67), or fasciocutaneous (FC; n = 76). Smoking, diabetes, peripheral vascular disease, and prior chemotherapy or radiation had no impact on complications, while osteomyelitis significantly increased the risk of infection (odds ratio [OR] 19.5, confidence interval [95% CI] 3.77-100.64; p = 0.0004), wound healing complications (OR 7.51, 95% CI 2.21-25.49; p = 0.001), and amputation (OR 4.63, 95% CI 1.41-15.19; p = 0.01). Hardware increased the risk for flap loss (OR 4.92, 95% CI 1.33-18.23; p = 0.017). MC and FC flaps had increased risks for hematoma (p = 0.02) and reoperation for microvascular complications (p = 0.005) but were at lower risk for infection (OR 0.14, 95% CI 0.02-0.87; p = 0.03) compared with muscle-only flaps. There were a total of seven total flap losses (3.2%), with significantly increased risks for MC/FC flaps (OR 2.58, 95% CI 1.06-6.26; p = 0.03). For LE, 103 patients (66.3%) were fully ambulatory, while 23 (14.7%) were ambulatory with assistance (mean Musculoskeletal Tumor Society score (MSTS) 80.2, and Karnofsky score 84.0). For UE, 49 patients (76.6%) were able to perform their activities of daily living independently (mean MSTS 80.2, and Karnofsky score 86.0). Overall, 190 patients (86.4%) were successfully salvaged. CONCLUSIONS: Free flaps can be performed reliably for limb salvage following tumor extirpation. While MC/FC flaps demonstrated improved postoperative function, they were at significantly higher risk for take-backs and total flap loss.

Patellar Height Decreasing After Distal Femur Endoprosthesis Reconstruction Does Not Affect Functional Outcome.

INTRODUCTION: The patellar height can influence extensor mechanism and the knee function. Thus, during knee arthroplasty, the surgeon seeks to maintain the correct patellar height. However, it is more difficult to define and maintain the correct patella height in megaprosthesis reconstructions after tumor resections. The objective of this study was to evaluate patellar height after distal femur endoprosthesis reconstruction and its association to knee function. METHODS: This retrospective analysis included 108 patients who underwent distal femur resections and endoprosthesis reconstruction. The minimum follow-up was 1 year or until the patients underwent patellar resurfacing or endoprosthesis revision. Patellar height was calculated using Insall-Salvati ratio (ISR) and Insall-Salvati patellar tendon insertion ratio (PTR) at 2 different times: postoperatively and at the final follow-up. The postoperative ratio was calculated using the best postoperative radiograph taken at least 1 month after the procedure. The final measures were based on the radiograph available at the last follow-up consultation. The ISR and PTR were associated to anterior knee pain (AKP), range of motion (ROM), and extension lag (EXL). RESULTS: The average follow-up was 4.5years. The mean postoperative ISR was 1.02, and the mean ISR at final follow-up was 0.95 (P<.0001). The mean postoperative PTR was 1.45, and the mean PTR at final follow-up was 1.40 (P=.016). There was no association between patellar height and AKP, ROM, and EXL. Patellar height decreases significantly after distal femur resections but does not affect AKP, ROM, and EXL.

Phase 1 adaptive dose-finding study of neoadjuvant gemcitabine combined with radiation therapy for patients with high-risk extremity and trunk soft tissue sarcoma.

BACKGROUND: This study was performed to determine the maximum tolerated dose (MTD) of gemcitabine given concurrently with preoperative, fixed-dose external-beam radiation therapy (EBRT) for patients with resectable, high-risk extremity and trunk soft tissue sarcoma (STS). METHODS: Gemcitabine was administered on days 1, 8, 22, 29, 43, and 50 with EBRT (50 Gy in 25 fractions over 5 weeks). The gemcitabine MTD was determined with a toxicity severity weight method (TSWM) incorporating 6 toxicity types. The TSWM is a Bayesian procedure that choses each cohort's dose to have a posterior mean total toxicity burden closest to a predetermined clinician-defined target. Clinicopathologic and outcome data were also collected. RESULTS: Thirty-six patients completed the study. According to the TSWM, the gemcitabine MTD was 700 mg/m(2). At this dose level, 4 patients (24%) experienced grade 4 toxicity; no toxicity-related deaths occurred. All tumors were resected with microscopically negative margins. Pathologic responses of >90% tumor necrosis were achieved in 17 patients (47%); 14 (39%) had complete responses. With a median follow-up of 6.2 years, the 5-year locoregional recurrence-free survival, distant metastasis-free survival, and overall survival rates were 85%, 80%, and 86%, respectively. CONCLUSIONS: The TSWM combines data from qualitatively different toxicities and can be used to determine the MTD for a drug given as part of a multimodality treatment. Neoadjuvant gemcitabine plus radiation therapy is feasible and safe in patients with high-risk extremity and trunk STS. Major pathologic responses can be achieved, and after complete resection, long-term clinical outcomes are encouraging.