Percutaneous Cementation for Improvement of Pain and Function for Osteolytic Pelvic Metastasis: A Systematic Review.

INTRODUCTION: Pelvic metastasis is a common presentation among patients presenting with skeletal metastasis. Image-guided percutaneous cementation of these lesions is becoming increasingly popular for the treatment of these lesions. The objective of this study was to conduct a systematic review that investigates clinical outcomes after percutaneous cementation for pelvic metastasis. METHODS: A systematic review was registered with International Prospective Register of Systematic Reviews and performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines using the PubMed, SCOPUS, and Ovid MEDLINE databases. All level I to IV clinical studies published in the English language investigating the clinical outcomes after percutaneous cementation for pelvic metastasis were included. RESULTS: Fourteen studies with 579 patients (278 men, 301 women) and 631 metastatic pelvic lesions were included in the study. The mean follow-up range was 0.7 to 26.4 months. Percutaneous cementation alone was performed in 441 patients (76.2%). Supplemental ablative procedures were performed in 77 patients (13.3%), and supplemental internal fixation using cannulated screws was performed in 107 patients (18.5%). Twelve studies with 430 patients (74.2%) reported pain-related and/or functional outcome scores, of which all studies reported overall clinically notable improvement at short-term follow-up. All studies reported periprocedural complications. Local cement leakage was the most common complication (162/631 lesions, 25.7%) followed by transient local pain (25/579 patients, 4.3%). There were no reported cases of major complications. Seven patients (1.2%) underwent re-intervention for persistent symptoms. CONCLUSIONS: Percutaneous cementation may be an effective method for treating pain and function related to pelvic metastasis. The most common complication was cement leakage surrounding the lesion. The rates of major complications were low, and most complications appeared minor and transient. Additional prospective studies are needed to further assess the efficacy of this procedure. LEVEL OF EVIDENCE: IV, systematic review of level I to IV therapeutic studies.

A randomized, non-comparative phase 2 study of neoadjuvant immune-checkpoint blockade in retroperitoneal dedifferentiated liposarcoma and extremity/truncal undifferentiated pleomorphic sarcoma.

Based on the demonstrated clinical activity of immune-checkpoint blockade (ICB) in advanced dedifferentiated liposarcoma (DDLPS) and undifferentiated pleomorphic sarcoma (UPS), we conducted a randomized, non-comparative phase 2 trial ( NCT03307616 ) of neoadjuvant nivolumab or nivolumab/ipilimumab in patients with resectable retroperitoneal DDLPS (n = 17) and extremity/truncal UPS (+ concurrent nivolumab/radiation therapy; n = 10). The primary end point of pathologic response (percent hyalinization) was a median of 8.8% in DDLPS and 89% in UPS. Secondary end points were the changes in immune infiltrate, radiographic response, 12- and 24-month relapse-free survival and overall survival. Lower densities of regulatory T cells before treatment were associated with a major pathologic response (hyalinization > 30%). Tumor infiltration by B cells was increased following neoadjuvant treatment and was associated with overall survival in DDLPS. B cell infiltration was associated with higher densities of regulatory T cells before treatment, which was lost upon ICB treatment. Our data demonstrate that neoadjuvant ICB is associated with complex immune changes within the tumor microenvironment in DDLPS and UPS and that neoadjuvant ICB with concurrent radiotherapy has significant efficacy in UPS.

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 .

ACR Appropriateness Criteria® Soft Tissue Masses: 2022 Update.

Imaging should be performed in patients with a suspected soft tissue mass that cannot be clinically confirmed as benign. Imaging provides essential information necessary for diagnosis, local staging, and biopsy planning. Although the modalities available for imaging of musculoskeletal masses have undergone progressive technological advancements in recent years, their overall purpose in the setting of a soft tissue mass remains unchanged. This document identifies the most common clinical scenarios related to soft tissue masses and the most appropriate imaging for their assessment on the basis of the current literature. It also provides general guidance for those scenarios that are not specifically addressed. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

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.

Reconstruction of Forequarter and Extended Forequarter Amputations: Indications and Outcomes.

BACKGROUND: Forequarter amputations (FQAs) and extended forequarter amputations (EFQAs) are rare procedures with high morbidity that often require significant soft-tissue or bony reconstruction. The authors describe the largest series of oncologic FQAs and EFQAs to date with associated reconstructive and oncologic outcomes. METHODS: The authors retrospectively reviewed data from all patients who underwent FQA or EFQA at The University of Texas M. D. Anderson Cancer Center from January 1, 2008, to January 1, 2019. Surgical outcomes, survival, and local recurrence rates were summarized and compared. RESULTS: Forty-seven patients met the inclusion criteria, including 14 with EFQAs. Most patients (53%) were male; the median age was 58 years (range, 2 to 74). The most common tumor type was sarcoma (79%), and the most common presentation was recurrent (34%). Nineteen patients (40%) had distant metastases. The median defect size was 351 cm 2 ; flap reconstruction was required in 30 patients (64%). Eight patients (17%) experienced immediate complications and 12 (26%) experienced delayed complications. The median overall survival (OS) time was 21 months and the 5-year OS rate was 28.1%. OS and disease-free survival were superior in the EFQA group (69.8% versus 11.6%, P = 0.017; 58.9% versus 9.8%, P = 0.014, respectively). Metastasis at presentation was the most important predictor of survival on multivariate analysis (OR, 3.98; P = 0.004). CONCLUSIONS: Patients with EFQA had better OS and disease-free survival than did patients with FQA, owing to a lower incidence of metastatic disease. This study suggests a benefit to more aggressive resection and reconstruction when disease is locally confined. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

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.

Surgical drainage after limb salvage surgery and endoprosthetic reconstruction: is 30 mL/day critical?

BACKGROUND: Periprosthetic infection is a major cause of failure after segmental endoprosthetic reconstruction. The purpose of this study is to determine whether certain aspects of drain output affect infection risk, particularly the 30 mL/day criterion for removal. METHODS: Two hundred and ninety-five patients underwent segmental bone resection and lower limb endoprosthetic reconstruction at one institution. Data on surgical drain management and occurrence of infection were obtained from a retrospective review of patients' charts and radiographs. Univariate and multivariate Cox regression analyses were performed to identify factors associated with infection. RESULTS: Thirty-one of 295 patients (10.5%) developed infection at a median time of 13 months (range 1-108 months). Staphylococcus aureus was the most common organism and was responsible for the majority of cases developing within 1 year of surgery. Mean output at the time of drain removal was 72 mL/day. Ten of 88 patients (11.3%) with ≤ 30 mL/day drainage and 21 of 207 patients (10.1%) with > 30 mL/day drainage developed infection (p = 0.84). In multivariate analysis, independent predictive factors for infection included sarcoma diagnosis (HR 4.13, 95% CI 1.4-12.2, p = 0.01) and preoperative chemotherapy (HR 3.29, 95% CI 1.1-9.6, p = 0.03). CONCLUSION: Waiting until drain output is < 30 mL/day before drain removal is not associated with decreased risk of infection for segmental endoprostheses of the lower limb after tumor resection. Sarcoma diagnosis and preoperative chemotherapy were independent predictors of infection.

Does a Custom Electronic Health Record Alert System Improve Physician Compliance With National Quality Measures for Palliative Bone Metastasis Radiotherapy?

PURPOSE: In an effort to promote cost-conscious, high-quality, and patient-centered care in the palliative radiation of painful bone metastases, the National Quality Forum (NQF) formed measure 1822 in 2012, which recommends the use of one of the four dose-fractionation schemes (30 Gy in 10 fractions, 24 Gy in 6 fractions, 20 Gy in 5 fractions, or 8 Gy in a single fraction). We investigated whether a custom electronic health record (EHR) alert system improved quality measure compliance among 88 physicians at a large academic center and institutional network. METHODS: In March 2018, a multiphase alert system was embedded in a custom web-based EHR. Prior to a course of palliative bone radiation, the alert system notified the user of NQF 1822 recommendations and, once prescription was completed, either affirmed compliance or advised a change in treatment schedule. Rates of compliance were evaluated before and after implementation of alert system. RESULTS: Of 2,399 treatment courses, 86.5% were compliant with NQF 1822 recommendations. There was no difference in rates of NQF 1822 compliance before or after implementation of the custom EHR alert (86.0% before March 2018 v 86.9% during and after March 2018, P = .551). CONCLUSION: There was no change in rates of compliance following implementation of a custom EHR alert system designed to make treatment recommendations based on national quality measure guidelines. To be of most benefit, future palliative bone metastasis decision aids should leverage peer review, target a clear practice deficiency, center upon high-quality practice guidelines, and allow flexibility to reflect the diversity of clinical scenarios.

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.

Extraskeletal Myxoid Chondrosarcomas: Combined Modality Therapy With Both Radiation and Surgery Improves Local Control.

OBJECTIVE: We evaluated our experience treating patients with localized extraskeletal myxoid chondrosarcomas (EMCs) to evaluate outcomes and relapse rates in order to better inform treatment decisions for these rare soft tissue sarcomas. MATERIALS AND METHODS: We reviewed the records of 41 consecutive patients with localized EMC treated at our institution from 1990 to 2016. Most patients (n=33, 80%) received combined modality therapy with surgery and radiation therapy, whereas only 8 (20%) underwent surgery alone. The Kaplan-Meier method was used to estimate rates of overall survival, disease-specific survival, local control (LC), and distant metastatic-free survival (DMFS). RESULTS: Median follow-up time was 94 months (range, 8 to 316). The 10-year LC, DMFS, disease-specific survival, and overall survival rates were 90%, 69%, 85%, and 66%, respectively. There were 5 patients (12%) with local relapse at a median time of 75 months (range, 13 to 176). On univariate analysis, the only significant factor associated with poorer LC was the use of surgery alone (10 y LC, 63% vs. 100% for combined modality therapy, P=0.004), which remained the only factor also significant on the multivariable analysis (P=0.02; hazard ratio [HR], 12.7; 95% confidence interval [CI], 1.4-115.3). In total, 13 patients (32%) developed distant metastatic at a median time of 28 months (range, 3 to 154). Interestingly, local recurrence was the only factor associated with poorer DMFS on multivariate analysis (P=0.04; HR, 3.9; 95% CI, 1.1-14.7). CONCLUSIONS: For patients with EMC, surgery alone was associated with a higher risk of local recurrence. Therefore, we recommend optimal local therapeutic strategies upfront with both surgery and radiation therapy to reduce the risk of local and ultimately distant recurrence.

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.

Single-Fraction Stereotactic vs Conventional Multifraction Radiotherapy for Pain Relief in Patients With Predominantly Nonspine Bone Metastases: A Randomized Phase 2 Trial.

Importance: Consensus is lacking as to the optimal radiotherapy dose and fractionation schedule for treating bone metastases. Objective: To assess the relative efficacy of high-dose, single-fraction stereotactic body radiotherapy (SBRT) vs standard multifraction radiotherapy (MFRT) for alleviation of pain in patients with mostly nonspine bone metastases. Design, Setting, and Participants: This prospective, randomized, single-institution phase 2 noninferiority trial conducted at a tertiary cancer care center enrolled 160 patients with radiologically confirmed painful bone metastases from September 19, 2014, through June 19, 2018. Patients were randomly assigned in a 1:1 ratio to receive either single-fraction SBRT (12 Gy for ≥4-cm lesions or 16 Gy for <4-cm lesions) or MFRT to 30 Gy in 10 fractions. Main Outcomes and Measures: The primary end point was pain response, defined by international consensus criteria as a combination of pain score and analgesic use (daily morphine-equivalent dose). Pain failure (ie, lack of response) was defined as worsening pain score (≥2 points on a 0-to-10 scale), an increase in morphine-equivalent opioid dose of 50% or more, reirradiation, or pathologic fracture. We hypothesized that SBRT was noninferior to MFRT. Results: In this phase 2 noninferiority trial of 96 men and 64 women (mean [SD] age, 62.4 [10.4] years), 81 patients received SBRT and 79 received MFRT. Among evaluable patients who received treatment per protocol, the single-fraction group had more pain responders than the MFRT group (complete response + partial response) at 2 weeks (34 of 55 [62%] vs 19 of 52 [36%]) (P = .01), 3 months (31 of 43 [72%] vs 17 of 35 [49%]) (P = .03), and 9 months (17 of 22 [77%] vs 12 of 26 [46%]) (P = .03). No differences were found in treatment-related toxic effects or quality-of-life scores after SBRT vs MFRT; local control rates at 1 and 2 years were higher in patients receiving single-fraction SBRT. Conclusions and Relevance: Delivering high-dose, single-fraction SBRT seems to be an effective treatment option for patients with painful bone metastases. Among evaluable patients, SBRT had higher rates of pain response (complete response + partial response) than did MFRT and thus should be considered for patients expected to have relatively long survival. Trial Registration: ClinicalTrials.gov identifier: NCT02163226.

Tumor-induced hypophosphatemic osteomalacia caused by a mesenchymal tumor of the mandible managed by a segmental mandibulectomy and microvascular reconstruction with a free fibula flap.

BACKGROUND: Tumor-induced osteomalacia is a rare paraneoplastic syndrome in which patients develop hypophosphatemia and osteomalacia. METHODS AND RESULTS: Here, we report a unique case of a 42-year-old man who presented to our institution with a 1-year history of pain in his ribs, hips, lower back, and feet. Radiologic examination revealed a decrease in bone density and multiple insufficiency fractures. Laboratory evaluation revealed hypophosphatemia, low serum 1,25 dihydroxy vitamin D3 , and elevated fibroblast growth factor 23 (FGF23). A positron emission tomography/CT scan showed increased uptake in the right mandibular third molar region. Panoramic radiography and CT scanning showed a lytic expansile bone lesion. A mandibular bone biopsy revealed a mixed connective tissue tumor. A right segmental mandibulectomy was performed, followed by microvascular reconstruction. The resection was confirmed by normalization of serum phosphate and FGF23. CONCLUSION: Successful management of this condition was achieved, with complete surgical resection of the tumor and reconstructive surgery.

Extraskeletal Osteosarcomas: A Case Made for Combined Modality Local Therapy With Radiation and Surgery.

OBJECTIVE: We evaluated our experience treating patients with extraskeletal osteosarcoma (ESOS) using combined modality local therapy, including surgery and radiation therapy (RT), to investigate local control (LC) and other survival endpoints. METHODS: We reviewed the records of 21 consecutive patients with nonmetastatic, ESOS treated with RT in combination with surgery at our institution from 1984 to 2015. Postoperative RT was used for 10 patients (48%) to a median dose of 60 Gy (range, 60 to 68 Gy). The other 11 patients (52%) received 50 Gy preoperatively. Seven patients (33%) were treated with neoadjuvant or adjuvant chemotherapy. Among the patients who received chemotherapy, all were treated with doxorubicin and ifosfamide for a median of 6 cycles (range, 4 to 6). RESULTS: Median follow-up time was 120 months (range, 6 to 200 mo). Larger tumor size (>5 cm) was associated with chemotherapy use (P=0.046). The 5-year LC, distant metastatic free survival, and disease-specific survival rates were 93%, 53%, and 62%, respectively. Only 1 patient (5%) had a local recurrence at 22 months. Nine patients (43%) developed distant metastases at a median time of 9 months (range, 1 to 30 mo) without any significant factors for reduced distant metastatic free survival. Following disease relapse, there were 2 patients who were ultimately salvaged, both of whom were treated with chemotherapy and surgery. CONCLUSIONS: RT in combination with surgery provides favorable LC for patients with ESOS. However, patients have a high rate of distant metastases with limited salvage.

The Accuracy and Clinical Utility of Intraoperative Frozen Section Analysis in Open Biopsy of Bone.

BACKGROUND: Open biopsy of bone is the diagnostic benchmark for the diagnosis of skeletal lesions. Intraoperative pathology consultation with frozen section analysis is commonly performed to confirm adequacy of lesional tissue and guide intraoperative decision making. The purpose of this study was to determine the accuracy and clinical utility of intraoperative frozen section during open bone biopsy. METHODS: A retrospective review of 485 open biopsies of osseous lesions from 474 patients between 1997 and 2014 was performed. Pathology reports, operative notes, and prebiopsy imaging were assessed to determine the accuracy rates of frozen section analysis compared with final pathology. Pearson chi-squared and Fisher exact tests were performed to compare the accuracy and clinical utility rates based on soft-tissue extension, previous biopsy, lesional consistency, disease, and location. RESULTS: Overall diagnostic yield of open bone biopsy was 95.3%. Frozen section analysis was accurate in 54.2%, equivocal positive in 21.2%, equivocal negative in 21.0%, and incorrect in 3.5% of cases. Previous nondiagnostic biopsy and the type of disease were found to have statistically significant effects on the accuracy of frozen section analysis. CONCLUSION: Frozen section analysis was diagnostic in approximately one half of open biopsy cases. Additional information in equivocal positive results suggests that frozen section analysis is helpful for intraoperative decision making (clinical utility) in 75.4% of cases. LEVEL OF EVIDENCE: Retrospective review level IV.

Long-Term Outcomes for Patients With Desmoid Fibromatosis Treated With Radiation Therapy: A 10-Year Update and Re-evaluation of the Role of Radiation Therapy for Younger Patients.

PURPOSE: To update our experience with long-term outcomes in patients with desmoid fibromatosis treated with radiation therapy (RT) and to characterize factors associated with increased risk of local recurrence. METHODS AND MATERIALS: We reviewed the records of 209 consecutive patients with desmoid fibromatosis treated with RT, either alone or as combined-modality therapy (CMT) with surgery, at our institution from 1965 to 2015. RESULTS: Median follow-up time was 98 months (range, 1-509 months). The 5- and 10-year local control (LC) was 71% and 69%, respectively. Fifty-nine patients (28%) experienced a local recurrence at a median time of 23 months (interquartile range, 15-38 months). Among all patients, on multivariable analysis, adjusting for anatomic site, size, age, treatment era (>2005 vs ≤2005), treatment approach (RT alone vs CMT), and an interaction between age and treatment, we found only age ≤30 years (hazard ratio [HR], 2.94; P = .005; 95% confidence interval [CI], 1.38-6.27) and large tumor size >10 cm (HR, 2.51; P = .03; 95% CI, 1.09-5.78) to be correlated with poorer LC. Notably, for patients receiving RT alone, the 5-year LC was 43% for patients ≤30 years old versus 75% for >30 years old (P < .001). On multivariable analyses, for patients receiving RT alone, the only factor associated with inferior LC was age ≤30 years (HR, 2.87; P = .001; 95% CI, 1.51-5.47). The same was true for patients treated with CMT; age ≤30 years was the only factor associated with inferior LC (HR, 5.36; P = .01; 95% CI, 1.40-20.58). CONCLUSIONS: Among all patients with desmoid fibromatosis, RT is an effective local therapy for tumor control. However, young patients ≤ 30 years have notably high rates of local recurrence regardless of treatment strategy, which requires further study. Treatment decisions should be risk-adapted by large referral centers with multidisciplinary expertise in desmoid management.

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.

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.