Local recurrence rates of superficial versus deep soft tissue sarcoma.

INTRODUCTION: Soft tissue sarcomas are a group of malignancies that commonly occur in the extremities. As deep lesions may exist within the confines of the muscular fascia, we postulate that local recurrence rates are higher for superficial soft tissue sarcomas managed by the standard of care. MATERIALS AND METHODS: A retrospective review was performed on 90 patients who underwent surgical resection of soft tissue sarcomas of the extremity from 2007 to 2015. Patients with minimum 2-year follow-up and adequate operative, pathologic, and clinical outcomes data were included. RESULTS: Mean age was 54 ± 18 years with 49 (54.4%) patients being male. Lesions in 77.8% of cases were deep, and 22.2% were superficial to fascia. Following the index surgical resection, a total of 33 (36.7%) patients had positive margins. A total of 17 (18.9%) patients had a local recurrence. Overall, 3-year survival was 92.7%, and 5-year survival was 79.0%. Five-year recurrence-free survival of deep sarcomas was 91.1% versus 58.2% of superficial lesions (p = 0.006). Patients with higher tumor depth had lower odds of experiencing a local recurrence (HR 0.26 [95% CI 0.09-0.72]). Local recurence rates was also associated with positive surgical margins on initial resection (33.3% versus 12.3%) (p = 0.027). CONCLUSIONS: In this series, superficial tumor depth was associated with local recurrence of soft tissue sarcomas of the extremity following surgical resection. Positive surgical margins was also associated with local recurrence.

Orthopedic Oncology Experience During Residency.

The objective of this study was to determine the characteristics and logistics of orthopedic oncology rotations at various residency programs across the USA and determine the effect of orthopedic oncology rotations on Orthopedic In-Training Examination (OITE) scores. An eight-question survey was sent to 162 orthopedic surgery residency programs obtained from the Accreditation Council for Graduate Medical Education public database. Pre-oncology rotation and post-oncology rotation OITE scores for 24 residents at a major academic medical center were collected and analyzed. The response rate was 43.8%. Survey results were as follows: 90.1% responded positively to having a dedicated orthopedic oncology rotation in their curriculum; 49.3% carried out their oncology rotation at a hospital outside of their home institution; 70.4% of programs had only one dedicated orthopedic oncology rotation throughout residency; 42.3% indicated that residents experience 6-10 weeks of dedicated orthopedic oncology training during the 5-year residency program; 42.2% indicated that residents experience oncology rotations during post-graduate year 4; and 80.3% of programs had orthopedic oncology trained surgeons on their faculty. The mean increase in OITE oncology scores after the rotation was 12.1% (p = 0.005). There are variations in orthopedic oncology curricula across residency programs, most notably in the number of weeks residents participate in a dedicated oncology rotation, the post-graduate year that residents rotate on an oncology service, and the location where residents obtain their orthopedic oncology training. Participating in a dedicated orthopedic oncology rotation resulted in significant improvement in scores on the oncology domain of the OITE.

Is Surgical Resection of the Primary Site Associated with an Improved Overall Survival for Patients with Primary Malignant Bone Tumors Who Have Metastatic Disease at Presentation?

BACKGROUND: The management of primary malignant bone tumors in patients with metastatic disease at presentation remains a challenge. Although surgical resection has been a mainstay in the management of nonmetastatic malignant bone tumors, there is a lack of large-scale evidence-based guidance on whether surgery of the primary site/tumor improves overall survival in malignant bone tumors with metastatic disease at presentation. QUESTIONS/PURPOSES: (1) Is surgical resection of the primary tumor associated with improved overall survival in patients with primary malignant bone tumors who have metastatic disease at presentation? (2) What other factors are associated with improved and/or poor overall survival? METHODS: The 2004 to 2016 National Cancer Database (NCDB), a national registry containing data from more than 34 million cancer patients in the United States, was queried using International Classification of Diseases, 3rd Edition, topographical codes to identify patients with primary malignant bone tumors of the extremities (C40.0-C40.3, C40.8, and C40.9) and/or pelvis (C41.4). The NCDB was preferred over other national cancer registries (that is, the Surveillance, Epidemiology, and End Results database) because it includes a specific variable that codes for patients who received additional surgeries at metastatic sites. Patients with malignant bone tumors of the head or skull, trunk, and spinal column were excluded because these patients are not routinely encountered and treated by orthopaedic oncologists. Histologic codes were used to categorize the tumors into the following groups: osteosarcomas, chondrosarcomas, and Ewing sarcomas. Patients whose tumors were classified as Stage 1, 2, or 3 based on American Joint Commission of Cancer guidelines were excluded. Only patients who presented with metastatic disease were included in the final study sample. The study sample was divided into two distinct groups: those who underwent surgical resection of the primary tumor and those who did not receive any operation for the primary tumor. A total of 2288 patients with primary malignant bone tumors (1121 osteosarcomas, 345 chondrosarcomas, and 822 Ewing sarcomas) with metastatic disease at presentation were included, of whom 46% (1053 of 2288) underwent surgical resection of the primary site. Thirty-three percent (348 of 1053) of patients undergoing surgical resection of the primary site also underwent additional resection of metastases. Patients undergoing surgical resection of the primary site typically were younger than 18 years, lived further from a facility, had tumors involving the upper or lower extremity, had a diagnosis of osteosarcoma or chondrosarcoma, and had a greater tumor size and higher tumor grade at presentation. To account for baseline differences within the patient population and to adjust for additional confounding variables, multivariate Cox regression analyses were used to assess whether undergoing surgical resection of the primary tumor was associated with improved overall survival, after controlling for differences in baseline demographics, tumor characteristics (grade, location, histologic type, and tumor size), and treatment patterns (resection of distant or regional metastatic sites, positive or negative surgical margins, and use of radiation therapy or chemotherapy). Additional sensitivity analyses, stratified by histologic type for osteosarcomas, chondrosarcomas, and Ewing sarcomas, were used to assess factors associated with overall survival for each tumor type. RESULTS: After controlling for differences in baseline demographics, tumor characteristics, and treatment patterns, we found that surgical resection of the primary site was associated with reduced overall mortality compared with those who did not have a resection of the primary site (hazard ratio 0.42 [95% confidence interval 0.36 to 0.49]; p < 0.001). Among other factors, in the stratified analysis, radiation therapy was associated with improved overall survival for patients with Ewing sarcoma (HR 0.71 [95% CI 0.57 to 0.88]; p = 0.002) but not for those with osteosarcoma (HR 1.14 [95% CI 0.91 to 1.43]; p = 0.643) or chondrosarcoma (HR 1.0 [95 % CI 0.78 to 1.50]; p = 0.643). Chemotherapy was associated with improved overall survival for those with osteosarcoma (HR 0.50 [95% CI 0.39 to 0.64]; p < 0.001) and those with chondrosarcoma (HR 0.62 [95% CI 0.45 to 0.85]; p = 0.003) but not those with Ewing sarcoma (HR 0.7 [95% CI 0.46 to 1.35]; p = 0.385). CONCLUSIONS: Surgical resection of the primary site was associated with an overall survival advantage in patients with primary malignant bone tumors who presented with metastatic disease. Further research, using more detailed data on metastatic sites (such as, size, location, number, and treatment), chemotherapy regimen and location of radiation (primary or metastatic site) is warranted to better understand which patients will have improved overall survival and/or a benefit in the quality of life from resecting their primary malignant tumor if they present with metastatic disease at diagnosis. LEVEL OF EVIDENCE: Level III, therapeutic study.

Targeted muscle reinnervation in oncologic amputees: Early experience of a novel institutional protocol.

BACKGROUND: We describe a multidisciplinary approach for comprehensive care of amputees with concurrent targeted muscle reinnervation (TMR) at the time of amputation. METHODS: Our TMR cohort was compared to a cross-sectional sample of unselected oncologic amputees not treated at our institution (N = 58). Patient-Reported Outcomes Measurement Information System (NRS, PROMIS) were used to assess postamputation pain. RESULTS: Thirty-one patients underwent amputation with concurrent TMR during the study; 27 patients completed pain surveys; 15 had greater than 1 year follow-up (mean follow-up 14.7 months). Neuroma symptoms occurred significantly less frequently and with less intensity among the TMR cohort. Mean differences for PROMIS pain intensity, behavior, and interference for phantom limb pain (PLP) were 5.855 (95%CI 1.159-10.55; P = .015), 5.896 (95%CI 0.492-11.30; P = .033), and 7.435 (95%CI 1.797-13.07; P = .011) respectively, with lower scores for TMR cohort. For residual limb pain, PROMIS pain intensity, behavior, and interference mean differences were 5.477 (95%CI 0.528-10.42; P = .031), 6.195 (95%CI 0.705-11.69; P = .028), and 6.816 (95%CI 1.438-12.2; P = .014), respectively. Fifty-six percent took opioids before amputation compared to 22% at 1 year postoperatively. CONCLUSIONS: Multidisciplinary care of amputees including concurrent amputation and TMR, multimodal postoperative pain management, amputee-centered rehabilitation, and peer support demonstrates reduced incidence and severity of neuroma and PLP.

Reverse total shoulder arthroplasty provides stability and better function than hemiarthroplasty following resection of proximal humerus tumors.

BACKGROUND: Tumors may necessitate resection of a substantial portion of the proximal humerus and surrounding soft tissues, making reconstruction challenging. We evaluated outcomes in patients undergoing treatment of tumors of the proximal humerus with reverse total shoulder arthroplasty (rTSA) or shoulder hemiarthroplasty. METHODS: Patients who underwent rTSA (n = 10) or shoulder hemiarthroplasty (n = 37) for tumors of the proximal humerus in 2009 to 2017 were reviewed. Of these patients, 27 had died, leaving 20 for review. The mean follow-up period of the survivors was 27.1 months. They were evaluated clinically and contacted to determine the American Shoulder and Elbow Surgeons score, Simple Shoulder Test score, and visual analog scale score. RESULTS: Postoperative complications occurred in 13 hemiarthroplasty patients (34%). Tumor recurrence occurred in 3 hemiarthroplasty patients (7.9%), whereas in the rTSA group, 1 patient (10%) had a postoperative complication, with no recurrences. One hemiarthroplasty patient required revision surgery with rTSA to improve shoulder function. Six dislocations and two subluxations occurred in the hemiarthroplasty group, whereas no subluxations occurred in the rTSA group (P = .14). Mean range of motion was 85° of forward flexion for rTSA patients (n = 10) compared with 28° for hemiarthroplasty patients (P < .001). The mean American Shoulder and Elbow Surgeons score was 63 for hemiarthroplasty patients (n = 5) and 59 for rTSA patients (n = 4). The mean Simple Shoulder Test scores were 3.8 and 2.4, respectively. The mean visual analog scale pain scores were 2.4 and 2.5, respectively. CONCLUSION: Reverse total shoulder arthroplasty can reproducibly reconstruct the shoulder in patients requiring oncologic proximal humerus resection. Patients have good outcomes, better range of motion, and no increase in instability rates compared with hemiarthroplasty.

Soft Tissue Sarcoma, Version 2.2018, NCCN Clinical Practice Guidelines in Oncology.

Soft tissue sarcomas (STS) are rare solid tumors of mesenchymal cell origin that display a heterogenous mix of clinical and pathologic characteristics. STS can develop from fat, muscle, nerves, blood vessels, and other connective tissues. The evaluation and treatment of patients with STS requires a multidisciplinary team with demonstrated expertise in the management of these tumors. The complete NCCN Guidelines for STS provide recommendations for the diagnosis, evaluation, and treatment of extremity/superficial trunk/head and neck STS, as well as intra-abdominal/retroperitoneal STS, gastrointestinal stromal tumors, desmoid tumors, and rhabdomyosarcoma. This portion of the NCCN Guidelines discusses general principles for the diagnosis, staging, and treatment of STS of the extremities, superficial trunk, or head and neck; outlines treatment recommendations by disease stage; and reviews the evidence to support the guidelines recommendations.

Oncologic reconstruction of the proximal humerus with a reverse total shoulder arthroplasty megaprosthesis.

BACKGROUND AND PURPOSE: Both malignant and benign tumors of the proximal humerus may necessitate resection of a substantial portion of the proximal humerus, making reconstruction options challenging. While hemiarthroplasty has been a classic treatment, reverse total shoulder replacement may provide better pain relief and function for these patients. METHODS: We utilize a two-surgeon approach for these challenging cases. The orthopedic oncologist resects the tumor. A shoulder-trained surgeon implants the reverse shoulder replacement. Modern implants, with large glenospheres and modular components, can allow reliable, straightforward reconstructions for these patients. We prefer 6 weeks of postoperative immobilization to decrease the risk of instability. RESULTS: We have completed 13 reverse total shoulder replacements for oncologic shoulder resections, with acceptable clinical outcomes and no complications to date. CONCLUSION: Reverse total shoulder replacement with long-stem, modular components can reliably and reproducibly reconstruct the shoulder in patients with oncologic resections of the proximal humerus.

NCCN Guidelines Insights: Bone Cancer, Version 2.2017.

The NCCN Guidelines for Bone Cancer provide interdisciplinary recommendations for treating chordoma, chondrosarcoma, giant cell tumor of bone, Ewing sarcoma, and osteosarcoma. These NCCN Guidelines Insights summarize the NCCN Bone Cancer Panel's guideline recommendations for treating Ewing sarcoma. The data underlying these treatment recommendations are also discussed.

When is hemiarthroplasty preferable to intramedullary prophylactic fixation of malignant lesions of the proximal femur?

BACKGROUND: Malignant hip lesions can be managed operatively by intramedullary (IM) nail fixation and hemiarthroplasty. METHODS: A retrospective review was performed on 86 patients who underwent hemiarthroplasty (n = 22) or IM nail fixation (n = 64) for prophylactic treatment of impending pathologic fracture due to malignant lesions of the hip. Cox proportional hazards and logistic regression modeling were performed to determine risk of death, fixation failure, pain relief, and return to ambulation without gait aids. RESULTS: Median survival time after surgery was 8.8 months (with no difference in survival between hemiarthroplasty and IM nail [adjusted Hazard Ratio 1.40, CI 0.72, 2.53; P = 0.31]). Hemiarthroplasty was associated with lower risk of pathologic fracture, fixation failure, or reoperation (adjusted HR 0.02, CI < 0.001, 0.48; P = 0.01). Hemiarthroplasty did not increase odds of unassisted ambulation compared to IM nail fixation (adjusted Odds Ratio [OR] 2.23, CI 0.56, 9.71; P = 0.26). The strongest predictor of postoperative ambulation was preoperative ambulation without aids (adjusted OR 28.9, CI 7.37, 161; P < 0.001). CONCLUSIONS: There is no difference in survival or likelihood of unassisted ambulation after prophylactic femoral fixation with IM nails versus hemiarthroplasty in patients with metastatic disease of proximal femur.

Acute Kidney Disease After Total Hip and Knee Arthroplasty: Incidence and Associated Factors.

BACKGROUND: The development of acute kidney disease (AKD) following total joint arthroplasty has not been well characterized in the literature. We sought to calculate the incidence and identify risk factors associated with postoperative AKD for patients undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA). METHODS: A total of 1000 consecutive cases (860 unique patients, including revisions) of TKA or THA performed between January 2010 and May 2016 were identified. Seventy-nine cases were excluded due to pre-existing kidney dysfunction and 23 additional cases were excluded due to incomplete data, resulting in 898 cases included in the study. There were 492 females and 406 males with a mean age of 58.1 years (range, 14-93 years). The Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease criteria and serum creatinine values were used to determine AKD status. Multiple logistic regression modeling was used to identify postoperative AKD risk factors. RESULTS: Overall incidence of postoperative AKD was 6.8% (n = 61). Use of perioperative angiotensin receptor blocker (ARBs) or angiotensin-converting enzyme inhibitors (ACEi) (odds ratio [OR] = 2.09; P = .030), increasing body mass index (BMI) (OR = 1.58 per 10 kg/m2; P = .014), and use of vancomycin perioperatively (OR = 1.91; P = .021) were associated with increased odds of development of postoperative AKD. CONCLUSION: A 6.8% incidence rate of postoperative AKD was noted in patients undergoing TKA or THA. Perioperative use of ARBs/ACEi, perioperative vancomycin use, and increased BMI were associated with increased odds of postoperative AKD.

Soft Tissue Sarcoma, Version 2.2016, NCCN Clinical Practice Guidelines in Oncology.

Soft tissue sarcomas (STS) are rare solid tumors of mesenchymal cell origin that display a heterogenous mix of clinical and pathologic characteristics. STS can develop from fat, muscle, nerves, blood vessels, and other connective tissues. The evaluation and treatment of patients with STS requires a multidisciplinary team with demonstrated expertise in the management of these tumors. The complete NCCN Guidelines for Soft Tissue Sarcoma (available at NCCN.org) provide recommendations for the diagnosis, evaluation, and treatment of extremity/superficial trunk/head and neck STS, as well as intra-abdominal/retroperitoneal STS, gastrointestinal stromal tumor, desmoid tumors, and rhabdomyosarcoma. This manuscript discusses guiding principles for the diagnosis and staging of STS and evidence for treatment modalities that include surgery, radiation, chemoradiation, chemotherapy, and targeted therapy.

Patterns of major wound complications following multidisciplinary therapy for lower extremity soft tissue sarcoma.

BACKGROUND AND OBJECTIVES: The purpose of this study was to determine the pattern and timing of major wound complications (MWCs) in patients at our institution who received multimodality treatment for lower extremity soft tissue sarcoma (LE-STS) and to evaluate the impact of MWCs on tumor control and patient outcomes. METHODS: The medical records of 102 LE-STS patients treated with limb-sparing surgery and radiation therapy were reviewed. MWCs were defined as secondary operations with anesthesia, seroma/hematoma aspiration, admission for IV antibiotics, or persistent deep packing. RESULTS: MWCs occurred in 22% of patients, with 45% of events occurring >120 days after resection. On multivariate analysis, preoperative external beam radiation therapy (EBRT) (OR 4.29, 95% CI 1.06-17.40, P = 0.042) and skin graft placement (OR 6.39, 95% CI 1.37-29.84, P = 0.018) were found to be independent predictors of MWCs. MWC occurrence did not predict for chronic toxicity and did not impact tumor control or survival. CONCLUSIONS: A considerable proportion of MWCs occur >120 days from surgical resection with preoperative EBRT and skin graft placement independent predictors for MWCs. While an additional source of morbidity, MWC occurrence did not impact tumor control, nor did it predict for chronic toxicity. J. Surg. Oncol. 2016;114:385-391. © 2016 Wiley Periodicals, Inc.

Percutaneous Doxycycline Treatment of Juxtaphyseal Aneurysmal Bone Cysts.

BACKGROUND: A recurrence rate of 19% to 23% has been reported in juxtaphyseal aneurysmal bone cysts (ABC) without en bloc resection or amputation. No percutaneous surgical techniques or drug treatments have demonstrated consistent bone healing with normal physeal growth and a recurrence rate of <19%. Doxycycline has properties that may make it an appropriate agent for percutaneous treatment of juxtaphyseal ABC in skeletally immature patients. METHODS: We retrospectively reviewed 16 patients who underwent percutaneous treatment of ABCs with doxycycline from 2006 to 2011. The mean age was 7.1 years (range, 2 to 15 y). There were 16 treatment locations: humerus (9), tibia (3), fibula (2), femur (1), and ulna (1). Sixteen patients completed treatment involving 102 treatment sessions (2 to 14 sessions per patient). Treatment response was evaluated radiographically by measuring the lytic component, thickness of involved cortex, and signs of bony remodeling, and evidence of physeal growth arrest. Recurrence was indicated by new areas of lytic destruction after completion of treatment. The minimum follow-up was 18 months (mean, 39 mo). RESULTS: All 16 patients demonstrated reduction in lytic destruction, bony healing, and bony remodeling. One patient demonstrated recurrent minimal lytic destruction after 20 months of observation. Seven patients (7/16, 44%) demonstrated physeal ABC involvement; 5 of 7 patients healed with a physeal bone bridge, all ≤15% of the physeal surface area, 1 with mild central physeal deformity. All patients with focal transphyseal ABC involvement (4/4, 100%) demonstrated focal bone bridge after treatment. No patient had diffuse physeal growth arrest; only patients with intraphyseal or transphyseal ABC involvement had focal physeal growth arrest. CONCLUSIONS: In this series, patients undergoing percutaneous doxycycline treatment of juxtaphyseal ABCs demonstrated ABC healing and a recurrence rate of 6% at >18 months. Patients without physeal ABC involvement demonstrated no evidence of physeal growth arrest.

Surgical management of soft tissue sarcomas: extremity sarcomas.

Wide surgical resection is the recommended treatment for extremity soft tissue sarcomas. Chemotherapy and/or radiotherapy may improve local control, but with marginal effect on overall survival. Advanced reconstructive techniques and multidisciplinary care, including plastic surgery, may allow a higher rate of limb salvage. This report focuses on surgical and reconstructive aspects in the multimodality care of extremity sarcomas.

Diagnosis and Management of Soft-tissue Masses.

Soft-tissue masses of the extremities are common entities encountered by nearly all providers of musculoskeletal patient care. Proper management of these lesions requires a specific process of evaluation. A detailed history and physical examination must be performed. Appropriate imaging studies must be obtained based on clinical indications. MRI is the imaging modality of choice for diagnosis of soft-tissue masses, with CT and ultrasonography used as secondary options. These modalities aid the clinician in developing an appropriate differential diagnosis and treatment plan. When the initial evaluation is inconclusive, biopsy must be performed. A diagnosis must be established before definitive treatment with surgical excision or, in rare cases, radiation therapy is performed. Clinicians without substantial experience in treating soft-tissue masses should consider referral to a musculoskeletal oncologist for specialized care when a definitive diagnosis of a benign lesion cannot be made. Several studies have shown that multidisciplinary care in specialized referral centers optimizes outcomes and diminishes comorbid complications.

Expression of cancer-testis antigens MAGEA1, MAGEA3, ACRBP, PRAME, SSX2, and CTAG2 in myxoid and round cell liposarcoma.

Myxoid and round-cell liposarcoma is a frequently encountered liposarcoma subtype. The mainstay of treatment remains surgical excision with or without chemoradiation. However, treatment options are limited in the setting of metastatic disease. Cancer-testis antigens are immunogenic antigens with the expression largely restricted to testicular germ cells and various malignancies, making them attractive targets for cancer immunotherapy. Gene expression studies have reported the expression of various cancer-testis antigens in liposarcoma, with mRNA expression of CTAG1B, CTAG2, MAGEA9, and PRAME described specifically in myxoid and round-cell liposarcoma. Herein, we further explore the expression of the cancer-testis antigens MAGEA1, ACRBP, PRAME, and SSX2 in myxoid and round-cell liposarcoma by immunohistochemistry in addition to determining mRNA levels of CTAG2 (LAGE-1), PRAME, and MAGEA3 by quantitative real-time PCR. Samples in formalin-fixed paraffin-embedded blocks (n=37) and frozen tissue (n=8) were obtained for immunohistochemistry and quantitative real-time PCR, respectively. Full sections were stained with antibodies to MAGEA1, ACRBP, PRAME, and SSX2 and staining was assessed for intensity (1-2+) and percent tumor positivity. The gene expression levels of CTAG2, PRAME, and MAGEA3 were measured by quantitative real-time PCR. In total, 37/37 (100%) of the samples showed predominantly strong, homogenous immunoreactivity for PRAME. There was a variable, focal expression of MAGEA1 (11%) and SSX2 (16%) and no expression of ACRBP. Quantitative real-time PCR demonstrated PRAME and CTAG2 transcripts in all eight samples: six tumors with high mRNA levels; two tumors with low mRNA levels. The gene expression of MAGEA3 was not detected in the majority of cases. In conclusion, myxoid and round-cell liposarcomas consistently express PRAME by immunohistochemistry as well as CTAG2 and PRAME by qualitative real-time PCR. This supports the use of cancer-testis antigen-targeted immunotherapy in the treatment of this malignancy.