Transcutaneous Oximetry Does Not Reliably Predict Wound-healing Complications in Preoperatively Radiated Soft Tissue Sarcoma.

BACKGROUND: Surgical wound-healing complications after tumor resections in tissue that has been preoperatively radiated are a major clinical problem. Most studies have reported that complications occur in more than 30% of patients undergoing such resections in the lower extremity. There is currently no available method to predict which patients are likely to have a complication. Transcutaneous oximetry has been identified in preliminary studies as potentially useful, but the available evidence on its efficacy for this application thus far is inconclusive. QUESTIONS/PURPOSES: (1) Does transcutaneous oximetry measurement below 25 mmHg at any location in the surgical wound bed predict a wound-healing complication? (2) Does recovery (increase) in transcutaneous oxygen measurement during the rest period between the end of radiation and the time of surgery protect against wound-healing complications? METHODS: A prospective, multi-institution study was coordinated to measure skin oxygenation at three timepoints in patients undergoing surgery for a lower extremity soft tissue sarcoma after preoperative radiation. Between 2016 and 2020, the five participating centers treated 476 patients for lower extremity soft tissue sarcoma. Of those, we considered those with a first-time sarcoma treated with radiation before limb salvage surgery as potentially eligible. Based on that, 21% (98 of 476) were eligible; a further 12% (56 of 476) were excluded because they refused to participate or ultimately, they were treated with a flap, amputation, or skin graft. Another 1% (3 of 476) of patients were lost because of incomplete datasets or follow-up less than 6 months, leaving 8% (39 of 476) for analysis here. The mean patient age was 62 ± 14 years, 62% (24 of 39) of the group were men, and 18% (7 of 39) of patients smoked cigarettes; 87% (34 of 39) of tumors were intermediate/high grade, and the most common histologic subtype was undifferentiated pleomorphic sarcoma. In investigating complications, a cutoff of 25 mmHg was chosen based on a pilot investigation that identified this value. All patients were assessed for surgical wound-healing complications, which were defined as: those resulting in a return to the operating room, initiation of oral or IV antibiotics, intervention for seroma, or prolonged wound packing or dressing changes. To answer the first research question, we compared the proportion of patients who developed a wound-healing complication between those patients who had any reading below 25 mmHg (7 of 39) and those who did not (32 of 39). To answer the second question, we compared the group with stable or decreased skin oxygenation (22 of 37 patient measurements [two patients missed the immediate postoperative measurement]) to the group that had increased skin oxygen measurement (15 of 37 measurements) during the period between the end of radiation and the surgical procedure; again, the endpoint was the development of a wound-healing complication. This study was powered a priori to detect an unadjusted odds ratio for wound-healing complications as small as 0.71 for a five-unit (5 mmHg) increase in TcO 2 between the groups, with α set to 0.05, ß set to 0.2, and a sample size of 40 patients. RESULTS: We found no difference in the odds of a wound-healing complication between patients whose transcutaneous oxygen measurements were greater than or equal to 25 mmHg at all timepoints compared with those who had one or more readings below that threshold (odds ratio 0.27 [95% confidence interval (CI) 0.05 to 1.63]; p = 0.15). There was no difference in the odds of a wound-healing complication between patients who had recovery of skin oxygenation between radiation and surgery and those who did not (OR 0.63 [95% CI 0.37 to 5.12]; p = 0.64). CONCLUSION: Transcutaneous oximetry cannot be considered a reliable test in isolation to predict wound-healing complications. This may be a function of the fact that transcutaneous oximetry samples a relatively small portion of the landscape in which a wound-healing complication could potentially arise. In the absence of a reliable diagnostic test, clinicians must still use their best judgment regarding surgical timing and work to address modifiable risk factors to avoid complications. The unanswered question that remains is whether there is a skin perfusion or oxygenation issue at the root of these complications, which seems likely. Alternative approaches that can assess the wound more broadly and in real time, such as fluorescent probes, may be deserving of further investigation. LEVEL OF EVIDENCE: Level II, diagnostic study.

The preoperative machine learning algorithm for extremity metastatic disease can predict 90-day and 1-year survival: An external validation study.

BACKGROUND: The prediction of survival is valuable to optimize treatment of metastatic long-bone disease. The Skeletal Oncology Research Group (SORG) machine-learning (ML) algorithm has been previously developed and internally validated. The purpose of this study was to determine if the SORG ML algorithm accurately predicts 90-day and 1-year survival in an external metastatic long-bone disease patient cohort. METHODS: A retrospective review of 264 patients who underwent surgery for long-bone metastases between 2003 and 2019 was performed. Variables used in the stochastic gradient boosting SORG algorithm were age, sex, primary tumor type, visceral/brain metastases, systemic therapy, and 10 preoperative laboratory values. Model performance was calculated by discrimination, calibration, and overall performance. RESULTS: The SORG ML algorithms retained good discriminative ability (area under the cure [AUC]: 0.83; 95% confidence interval [CI]: 0.76-0.88 for 90-day mortality and AUC: 0.84; 95% CI: 0.79-0.88 for 1-year mortality), calibration, overall performance, and decision curve analysis. CONCLUSION: The previously developed ML algorithms demonstrated good performance in the current study, thereby providing external validation. The models were incorporated into an accessible application (https://sorg-apps.shinyapps.io/extremitymetssurvival/) that may be freely utilized by clinicians in helping predict survival for individual patients and assist in informative decision-making discussion before operative management of long bone metastatic lesions.

What is the likelihood of nonpulmonary metastasis occurring in the absence of lung metastasis in bone and soft tissue sarcoma? A nested case-control from a sarcoma referral centre.

BACKGROUND AND OBJECTIVES: Nonpulmonary metastases (NPM) are rare, associated with a poorer prognosis, and maybe missed on conventional chest imaging for sarcoma surveillance. We determined (1) the proportion of NPM occurring in isolation or with synchronous or prior pulmonary metastases (PM), and (2) if initial NPM would have been recognized with a standard surveillance protocol. METHODS: Investigators identified patients who developed initial NPM without prior evidence of or concurrent PM from an ongoing cohort of bone and soft tissue sarcoma (STS) patients. Logistic regression at univariate level was done. RESULTS: There were 138/630 (22%) patients with metastasis and 66 (10%) had NPM: 50 (8%) patients had PM presenting first, while 16 (3%) had initial NPM. Malignant peripheral nerve sheath tumor, angiosarcoma, rhabdomyosarcoma, synovial sarcoma, and myxoid liposarcoma were six times more likely to develop initial NPM than other subtypes of STS with odds ratio = 6 (95% confidence interval: 1.93-18.65, p value < 0.01). Chest imaging and physical examination were sufficient to identify NPM in all except three bone sarcoma patients. CONCLUSIONS: Patients who develop initial NPM are rare and demonstrate a predilection towards some subtypes of extremity sarcoma. They develop oligometastatic disease, which may be amenable for surgical excision. All isolated or initial NPM in STS patients were discovered by physical examination and standard chest imaging.

Is local recurrence in bone and soft tissue sarcomas just a local recurrence or does it impact the overall survival, retrospective cohort from a sarcoma referral center.

BACKGROUND AND OBJECTIVES: Sarcoma local recurrence (LR) is often associated with metastasis, but it is unclear if LR can be a causal event leading to metastasis. We question if LR is best viewed as an independent oncologic event or as a worrisome harbinger threatening a patient's overall survival. METHODS: We identified patients with LR and/or metastasis from an ongoing cohort of 629 patients with primary sarcoma and performed a detailed review to assess the timing of metastasis resulting in the following groups: (1) Isolated LR, (2) LR before metastasis, (3) LR within 6 months of metastasis, (4) LR 6-12 months after metastasis, (5) LR >12 months after metastasis, and (6) metastasis at diagnosis. RESULTS: Overall, 43 patients met the inclusion criteria with an LR rate of 7%. Ten patients (2% of the entire cohort, 23% of LR) developed an LR before or within 6 months of metastasis. For patients without systemic disease preceding LR, 3 of 23 soft tissue sarcoma STS (13%) and 7 of 10 bone sarcoma (70%) subsequently developed metastasis (p < 0.01). CONCLUSION: LR with subsequent metastasis is a rare event. LR appears to be best viewed as a marker of tumor aggressiveness rather than the cause of metastasis and poor survival. LR in bone sarcoma patients should warn providers of a high risk of imminent metastasis.

Sarcopenia is associated with increased mortality but not complications following resection and reconstruction of sarcoma of the extremities.

BACKGROUND AND OBJECTIVES: Evidence regarding the impact of sarcopenia on operative outcomes in patients with sarcoma is lacking. We evaluated the relationship between sarcopenia and postoperative complications or mortality among patients undergoing tumor excision and reconstruction. ​ METHODS: We retrospectively reviewed 145 patients treated with tumor excision and limb reconstruction for sarcoma of the extremities. Sarcopenia was defined as psoas index (PI) < 5.45 cm2 /m2 for men and <3.85 cm2 /m2 for women from preoperative axial CT. Regression analyses were used to assess the association between postoperative complications or mortality with PI, age, gender, race, body mass index, tumor histology, grade, depth, location, size, and neoadjuvant/adjuvant therapy. RESULTS: There were 101 soft tissue tumors and 44 primary bone tumors. Sarcopenia was present in 38 patients (26%). Sarcopenic patients were older (median age: 72 vs 59 years, P = .0010) and had larger tumors (86.5%, >5 cm vs 77.7%, P = .023). Seventy-three patients experienced complications (51%) and 18 patients died within 1 year. Sarcopenia and metastatic disease were associated with increased 12-month mortality (hazard ratio [HR] = 6.68, P < .001; HR: 8.51, P < .001, respectively) but not complications (HR 1.45, P = .155, odds ratio, 1.32, P = .426, respectively). CONCLUSIONS: Sarcopenia and metastatic disease were independently associated with postoperative mortality but no complications following surgery.

Acceptance and Commitment Therapy Delivered via a Mobile Phone Messaging Robot to Decrease Postoperative Opioid Use in Patients With Orthopedic Trauma: Randomized Controlled Trial.

BACKGROUND: Acceptance and commitment therapy (ACT) is a pragmatic approach to help individuals decrease avoidable pain. OBJECTIVE: This study aims to evaluate the effects of ACT delivered via an automated mobile messaging robot on postoperative opioid use and patient-reported outcomes (PROs) in patients with orthopedic trauma who underwent operative intervention for their injuries. METHODS: Adult patients presenting to a level 1 trauma center who underwent operative fixation of a traumatic upper or lower extremity fracture and who used mobile phone text messaging were eligible for the study. Patients were randomized in a 1:1 ratio to either the intervention group, who received twice-daily mobile phone messages communicating an ACT-based intervention for the first 2 weeks after surgery, or the control group, who received no messages. Baseline PROs were completed. Two weeks after the operative intervention, follow-up was performed in the form of an opioid medication pill count and postoperative administration of PROs. The mean number of opioid tablets used by patients was calculated and compared between groups. The mean PRO scores were also compared between the groups. RESULTS: A total of 82 subjects were enrolled in the study. Of the 82 participants, 76 (38 ACT and 38 controls) completed the study. No differences between groups in demographic factors were identified. The intervention group used an average of 26.1 (SD 21.4) opioid tablets, whereas the control group used 41.1 (SD 22.0) tablets, resulting in 36.5% ([41.1-26.1]/41.1) less tablets used by subjects receiving the mobile phone-based ACT intervention (P=.004). The intervention group subjects reported a lower postoperative Patient-Reported Outcome Measure Information System Pain Intensity score (mean 45.9, SD 7.2) than control group subjects (mean 49.7, SD 8.8; P=.04). CONCLUSIONS: In this study, the delivery of an ACT-based intervention via an automated mobile messaging robot in the acute postoperative period decreased opioid use in selected patients with orthopedic trauma. Participants receiving the ACT-based intervention also reported lower pain intensity after 2 weeks, although this may not represent a clinically important difference. TRIAL REGISTRATION: ClinicalTrials.gov NCT03991546; https://clinicaltrials.gov/ct2/show/NCT03991546.

What Is the Clinical Importance of Incidental Findings on Staging CT Scans in Patients With Sarcoma?

BACKGROUND: Baseline staging CT scans are performed on nearly every patient after the diagnosis of a sarcoma to evaluate for the presence of metastatic disease. These scans often identify abnormalities that may or may not be related to the known malignancy. Despite the high frequency of incidental findings, there is little guidance for clinicians faced with assessing these radiographic abnormalities. The interpretation of incidental findings is important because it may influence decisions regarding surveillance frequency, prognostic estimation, and surgical and medical intervention. QUESTIONS/PURPOSES: The purpose of this study was to determine (1) the frequency of abnormal findings and indeterminate nodules on staging CT scans; (2) the natural history of indeterminate nodules identified at the time of sarcoma diagnosis; and (3) the factors associated with indeterminate nodules representing true metastatic disease. METHODS: Between September 2010 and February 2016 we treated 233 patients with bone and soft tissue sarcomas. Of those, 227 (97%) had a staging CT scan of the chest or chest/abdomen/pelvis performed within 2 months of diagnosis. To be eligible for this retrospective study, a patient had to have a minimum of 6 months of radiographic followup after that initial CT scan. A total of 36 (16%) were lost to followup or did not have radiographic surveillance at least 6 months later, and 48 (21%) were excluded for other prespecified reasons, leaving 149 patients for evaluation. We recorded all abnormal findings listed in the official radiology CT report of the lung, bone, liver, and lymph nodes. We assessed progression of indeterminate nodules by reviewing radiology reports, which listed both size and number of findings, and clinical notes outlining the current assessment of disease status and treatment plan. If indeterminate nodules grew in size or number consistent with metastatic disease or were confirmed histologically, they were considered to represent true metastasis. Bivariate methods were used to investigate an association between various clinical factors, which were obtained from chart review, and progression of indeterminate nodules to clear metastatic disease. RESULTS: One hundred thirty-five of 149 patients (91%) had at least one abnormal finding on a staging CT scan. Forty-nine patients (33%) presented with indeterminate lung nodules, 15 (10%) with indeterminate liver lesions, four (3%) with indeterminate bone lesions, and 57 (38%) with enlarged lymph nodes. Fifteen of the 49 patients with indeterminate lung nodules (31%), one of 15 liver nodules, zero of four bone lesions, four of 13 lymph nodes 1 to 2 cm in size, and two of 44 subcentimeter lymph nodes (4.5%) were clearly metastatic on followup. A primary tumor size ≥ 14 cm in greatest dimension was more suggestive of indeterminate nodules representing true metastatic disease compared with smaller primary tumors in both lung (eight of 10 compared with seven of 36 [19%]; odds ratio, 16.6; 95% confidence interval, 2.9-95.9; p < 0.001) and lymph nodes (six of 18 compared with zero of 36 [0%], p < 0.001). CONCLUSIONS: It is extremely common for abnormal findings and incidental nodules to be present at the time of a staging CT scan in patients with sarcoma. Although patients with indeterminate nodules should have continued surveillance, it appears from this study that the majority of these findings do not represent true metastatic disease. Given a minimum followup of 6 months, it is possible the actual proportion of indeterminate lesions representing true metastatic disease may increase over time. LEVEL OF EVIDENCE: Level III, prognostic study.

Epidemiology, Therapeutic Strategies, Outcomes, and Complications of Pathologic Fractures.

Much can be learned about the epidemiology of metastatic disease of bone through large databases. Secondary data analyses add substantial knowledge of the incidence, prevalence, cost, complications, risk factors, and treatment variability by using modern statistical methods in a large patient cohort. Investigators must be aware of the intentions of these data sources as well as the limitations in any conclusions drawn. Large databases are primarily beneficial in generating hypotheses and will likely continue to be an important source of information. For the general orthopaedist, surgical management of metastatic skeletal disease can be a challenging problem with many potential risks. Complications are often encountered and can be influenced by the patient's medical conditions, stage of disease, and the selected surgical procedure. Patients diagnosed with skeletal metastases are often at higher risk of having perioperative complications, such as infection and thromboembolism, than is the general population. A case-based approach highlights potential risks with examples of common scenarios that can arise.

The association between feeding protocol compliance and weight gain following high-risk neonatal cardiac surgery.

BACKGROUND: Children with congenital heart disease are at high risk for malnutrition. Standardisation of feeding protocols has shown promise in decreasing some of this risk. With little standardisation between institutions' feeding protocols and no understanding of protocol adherence, it is important to analyse the efficacy of individual aspects of the protocols. METHODS: Adherence to and deviation from a feeding protocol in high-risk congenital heart disease patients between December 2015 and March 2017 were analysed. Associations between adherence to and deviation from the protocol and clinical outcomes were also assessed. The primary outcome was change in weight-for-age z score between time intervals. RESULTS: Increased adherence to and decreased deviation from individual instructions of a feeding protocol improves patients change in weight-for-age z score between birth and hospital discharge (p = 0.031). Secondary outcomes such as markers of clinical severity and nutritional delivery were not statistically different between groups with high or low adherence or deviation rates. CONCLUSIONS: High-risk feeding protocol adherence and fewer deviations are associated with weight gain independent of their influence on nutritional delivery and caloric intake. Future studies assessing the efficacy of feeding protocols should include the measures of adherence and deviations that are not merely limited to caloric delivery and illness severity.

Improved survival for extremity soft tissue sarcoma treated in high-volume facilities.

BACKGROUND AND OBJECTIVES: The purpose of this investigation was to determine the effect of hospital volume on treatment decisions, treatment results, and overall patient survival in extremity soft tissue sarcoma. METHODS: The National Cancer Database was used to identify patients ≥18 years of age with non-metastatic soft tissue sarcoma of the extremity treated with surgery. Patients in high- and low-volume centers were matched by propensity score and placed into two equal comparative groups of 2437 patients each. RESULTS: Chemotherapy was used at a higher rate in high-volume centers (22% vs 17%, P < 0.001) and external beam radiation usage was similar (55% vs 52%, P = 0.108). There was a lower incidence of positive margins in high-volume centers (12% vs 17%, P < 0.001). There was no significant difference in the rates of limb salvage surgery or readmissions at high-volume hospitals compared to low-volume. In a multivariate Cox proportional hazards model, low-volume facilities demonstrated diminished overall survival at all time points (hazard ratio at 5 years = 1.24, 95%CI 1.10-1.39). CONCLUSIONS: Treatment at high-volume hospitals was associated with fewer positive margins and increased overall survival at 2, 5, and 10 years. Continued efforts should focus on optimizing the balance between patient access to specialty care and experience of the treating center.

Anchored multiplex PCR for targeted next-generation sequencing reveals recurrent and novel USP6 fusions and upregulation of USP6 expression in aneurysmal bone cyst.

Primary aneurysmal bone cyst (ABC) is a neoplastic process due to recurrent translocations involving the USP6 gene. By fluorescence in situ hybridization, up to 69% of primary ABCs harbored USP6 translocations; no USP6 translocation was found in secondary ABC or giant cell tumor of bone (GCT). GCT can recur locally, metastasize to the lungs in some cases, and rarely undergo malignant transformation. Differentiating primary ABC from its mimics is important for treatment and prognosis. We evaluated USP6 fusion and expression in 13 cases of primary and 1 case of secondary ABC, and 9 cases of GCT using nucleic acid extracted from formalin-fixed, paraffin-embedded tissue and a next generation sequencing (NGS)-based assay. USP6 fusions including 7 novel fusions and USP6 transcripts were identified in all 13 primary ABCs. Nine cases with strong evidence of fusions showed high levels of USP6 transcripts by reverse transcription-PCR (RT-PCR). The remaining four had no detectable USP6 expression by a first-round of RT-PCR but the presence of USP6 transcripts was identified by a second-round, nested PCR. The major fusions were confirmed by RT-PCR followed by Sanger sequencing. No USP6 fusion or transcript was detected in any of the GCTs or the case of secondary ABC by NGS or by two rounds of PCR. All USP6 translocations resulted in fusion of the entire USP6 coding sequence with promoters of the fusion gene leading to upregulation of USP6 transcription, which is likely the underlying mechanism for ABC oncogenesis. © 2016 Wiley Periodicals, Inc.

Does surgery or radiation provide the best overall survival in Ewing's sarcoma? A review of the National Cancer Data Base.

BACKGROUND AND OBJECTIVES: There is continuing debate regarding the ideal modality for local control of the primary tumor for patients with Ewing's sarcoma. The primary aim of this study is to investigate the impact of the method of local control on overall survival in patients with Ewing's sarcoma. METHODS: The National Cancer Data Base was used to identify patients <40 years of age with high-grade Ewing's sarcoma of bone. A Kaplan-Meier survival analysis was performed at 2, 5, and 10 years. Factors with a level of significance of P < 0.1 at the 5-year time point were included in a multivariate Cox proportional hazards model. RESULTS: Diminished 5-year survival was noted for patients with metastatic disease, local control with radiation alone, age ≥18 years, tumor size >8 cm, and male sex while controlling for tumor site. Surgery alone was consistently the method of local control that resulted in the highest overall survival. CONCLUSIONS: Surgery alone resulted in the best overall survival for patients with Ewing's sarcoma of bone. The results of this investigation provide support to the approach of surgical resection with negative margins when possible.

Are Recently Trained Tumor Fellows Performing Less Tumor Surgery? An Analysis of 10 Years of the ABOS Part II Database.

BACKGROUND: The majority of orthopaedic trainees pursue additional subspecialty training at the conclusion of residency. Although national trends indicate that fellowship-trained surgeons are more frequently performing cases in their defined subspecialties, this may not be the case for recently trained tumor fellows. Prior work has established that low tumor case volume is a significant stressor for recently trained tumor fellows. Given the relative rarity of musculoskeletal tumors, it is important for prospective trainees to have clear expectations for the proportion of specialty-specific procedures early during their careers. In addition, knowledge of anticipated specialty case volume is important to optimize fellowship training and to provide guidance for meeting the public health requirements for orthopaedic oncology. QUESTIONS/PURPOSES: We wished to determine (1) the number of examinees who self-reported tumor fellowship training during the last decade; (2) how many tumor fellowship-educated surgeons did an additional fellowship(s) in other subspecialties; (3) the number and proportion of tumor, trauma, adult reconstruction, and other procedures performed by tumor-trained fellows; and (4) changes in the proportion of procedures performed by tumor-trained fellows during the 10-year period of the study. METHODS: The American Board of Orthopaedic Surgery Part II database was used to identify examinees who reported tumor fellowship training between 2004 and 2013. All submitted procedures were broadly categorized as "tumor," "trauma," "adult reconstruction," or "other." Annual procedure volumes were calculated and univariate analysis allowed comparison of categorized procedures during the duration of the study. RESULTS: The median annual number of candidates reporting tumor fellowship training was 12.5 (range, 7-16). There were 28 of 118 (24%) candidates who reported additional fellowship training. A total of 14,718 procedures were performed by all candidates with tumor fellowship training during the 10-year period of the study, 42% of which were categorized as tumor procedures. Overall, only 36% of candidates reported tumor procedures making up greater than 50% of their case volume. Between 2004 to 2005 and 2012 to 2013, the proportion of tumor procedures decreased (45% versus 36%; p < 0.001), whereas the number of adult reconstruction procedures increased (9% versus 19%; p < 0.001). CONCLUSIONS: Between 2004 and 2013, only one-third of recently trained tumor fellows had practices with tumor procedures accounting for greater than 50% of their total case volume. Furthermore, the proportion of tumor cases performed by recently trained tumor fellows decreased during the same time. The proportion of specialty-specific procedures is lower in orthopaedic oncology than other orthopaedic subspecialties, which is important information for current trainees interested in orthopaedic oncology fellowship training and for orthopaedic oncology educators. The findings in this study should serve as an initial platform for further discussion regarding the optimal number of fellowship-trained orthopaedic oncologists required to meet regional and national needs for an accessible and proficient work force.

Minimizing Blood Transfusion in Total Hip and Knee Arthroplasty Through a Multimodal Approach.

BACKGROUND: We introduced a multimodal, multidisciplinary approach to perioperative blood management aimed at reducing blood transfusions in primary knee (TKA) and hip (THA) arthroplasty. The protocol included (1) preoperative hemoglobin optimization through a multidisciplinary approach, (2) minimization of perioperative blood loss, and (3) adherence to evidence-based transfusion guidelines. METHODS: Evaluation of 1010 consecutive patients undergoing primary TKA (488) or THA (522) was performed. RESULTS: A significant reduction in the overall transfusion rate (1.4% vs 17.9%, P<.0001) resulted after algorithm introduction, when compared with the 1814 previous patients. Zero (0%) TKA and 4 (0.8%) THA patients adherent to protocol, and 4/488 (0.8%) TKA and 10/522 (1.9%) THA patients overall received transfusions. CONCLUSION: Adoption of a multimodal blood management algorithm can significantly reduce blood transfusions in primary joint arthroplasty.

How much tumor surgery do early-career orthopaedic oncologists perform?

BACKGROUND: There are few data on the types of procedures orthopaedic oncologists perform in their first years of practice. Because fellowships are graduating fellows each year and the number of tumor patients is limited, defining the practice patterns of early-career orthopaedic oncologists may help diminish early employment discontent and enhance workforce discussions. QUESTIONS/PURPOSES: The aim of the study was to use the objective case log volumes of a cross-section of early career orthopaedic oncologists to describe (1) the number of operations performed annually; (2) the proportion of tumor, trauma, adult reconstruction, and other operations for individual participants, (3) individual practice characteristics that were associated with the number of tumor procedures; and (4) the sources of satisfaction and challenges in each individual's career and surgical practice. METHODS: Fifteen fellowship-trained orthopaedic oncologists out of a potential pool of 33 (45%) in their first 4 years of practice responded to a survey by submitting complete operative case lists for a 2-year period. We recorded the type of procedure and determined associations between the annual number of tumor operations and total operative caseload, years in practice, and some details of individual practice patterns. Each participant completed a survey regarding practice-related sources of stress and satisfaction. A total of 5611 surgical cases were available for review. For the entire cohort, there were 3303 (59%) tumor procedures, 973 (17%) trauma, 890 (16%) adult reconstruction, and 445 (8%) other. RESULTS: The median annual number of total operations was 214 (range, 63-356) and median annual number of tumor operations was 135 (range, 47-216). The median proportion of tumor operations in an individual practice was 56% (range, 43%-94%). The annual number of tumor operations correlated with the total annual number of operations (r = 0.73, p < 0.001). Sources of stress and satisfaction were similar to the general membership of the Musculoskeletal Tumor Society (MSTS), apart from more early-career surgeons regarding case volume as important (29 of 104 [28%] of MSTS versus 11 of 15 [73%] of early-career, p < 0.001). CONCLUSIONS: The typical early-career orthopaedic tumor surgeon had fewer than 60% of his or her operative procedures directly related to the subject of his or her fellowship training in orthopaedic oncology. Overall, the challenges and rewards of clinical practice are similar to oncologic surgeons later in their career. This study is a first step in assessing early practice characteristics and may be of value to the prospective orthopaedic oncologist, fellowship educators, and the society in workforce discussions. Early-career practice patterns have not been previously presented, to our knowledge, for any subspecialty of orthopaedic surgery, and we hope that this study will stimulate similar efforts throughout the field. LEVEL OF EVIDENCE: Level IV, economic and decision analyses. See Guidelines for Authors for a complete description of levels of evidence.

What is the use of imaging before referral to an orthopaedic oncologist? A prospective, multicenter investigation.

BACKGROUND: Patients often receive advanced imaging before referral to an orthopaedic oncologist. The few studies that have evaluated the value of these tests have been single-center studies, and there were large discrepancies in the estimated frequencies of unnecessary use of diagnostic tests. QUESTIONS/PURPOSES: (1) Is there regional variation in the use of advanced imaging before referral to an orthopaedic oncologist? (2) Are these prereferral studies helpful to the treating orthopaedic oncologist in making a diagnosis or treatment plan? (3) Are orthopaedic surgeons less likely to order unhelpful studies than other specialties? (4) Are there any tumor or patient characteristics that are associated with the ordering of an unhelpful study? METHODS: We performed an eight-center prospective analysis of patients referred for evaluation by a fellowship-trained orthopaedic oncologist. We recorded patient factors, referral details, advanced imaging performed, and presumptive diagnosis. The treating orthopaedic oncologist determined whether each study was helpful in the diagnosis or treatment of the patient based on objective and subjective criteria used in prior investigations. We analyzed the data using bivariate methods and logistic regression to determine regional variation and risk factors predictive of unhelpful advanced imaging. Of the 371 participants available for analysis, 301 (81%) were referred with an MRI, CT scan, bone scan, ultrasound, or positron emission tomography scan. RESULTS: There were no regional differences in the use of advanced imaging (range of patients presenting with advanced imaging 66%-88% across centers, p = 0.164). One hundred thirteen patients (30%) had at least one unhelpful study; non-MRI advanced imaging was more likely to be unhelpful than MRIs (88 of 129 [68%] non-MRI imaging versus 46 of 263 [17%] MRIs [p < 0.001]). Orthopaedic surgeons were no less likely than nonorthopaedic surgeons to order unhelpful studies before referral to an orthopaedic oncologist (56 of 179 [31%] of patients referred by orthopaedic surgeons versus 35 of 119 [29%] referred by primary care providers and 22 of 73 [30%] referred by nonorthopaedic specialists, p = 0.940). After controlling for potential confounding variables, benign bone lesions had an increased odds of referral with an unhelpful study (59 of 145 [41%] of benign bone tumors versus 54 of 226 [24%] of soft tissue tumors and malignant bone tumors; odds ratio, 2.80; 95% confidence interval, 1.68-4.69, p < 0.001). CONCLUSIONS: We found no evidence that the proportion of patients referred with advanced imaging varied dramatically by region. Studies other than MRI were likely to be considered unhelpful and should not be routinely ordered by referring physicians. Diligent education of orthopaedic surgeons and primary care physicians in the judicious use of advanced imaging in benign bone tumors may help mitigate unnecessary imaging. LEVEL OF EVIDENCE: Level III, diagnostic study. See Guidelines for Authors for a complete description of levels of evidence.

Estimated cause-specific survival continues to improve over time in patients with chondrosarcoma.

BACKGROUND: Conditional survival measures change in the risk of mortality given that a patient has survived a defined period of time. This has yet to be reported for chondrosarcoma of bone. This information should be of interest to the clinician and helpful in counseling patients with chondrosarcoma. QUESTIONS/PURPOSES: Our questions include the following: (1) Does the conditional survival of patients with local/regional chondrosarcoma improve with each additional year of survival? (2) Does the conditional survival of patients with metastatic chondrosarcoma improve with each additional year of survival? (3) Does tumor location, use of radiation, or patient age affect conditional survival? (4) Can chondrosarcoma ever be considered cured? METHODS: We used the Surveillance, Epidemiology, and End Results Program database maintained by the National Cancer Institute to identify 2138 patients with chondrosarcoma of bone from 1973 to 2009. We used an actuarial life table analysis to explore differences in 5-year cause-specific survival estimates conditional on 1 to 5 years of survival. The cohort was stratified by grade, location (axial versus extremity), use of radiation, and age. Finally, we expanded the analysis to include survival estimates 20 years after diagnosis conditional on survival for 5 and 10 years. RESULTS: The estimated survival for all grades of local/regional chondrosarcoma improved from baseline with each year of survival after diagnosis. At 5 years after diagnosis, local/regional Grade 1 chondrosarcoma displayed higher conditional survival than Grade 2 and 3 local/regional chondrosarcoma (97.2% [95% confidence interval {CI}, 95.2%-98.4%] versus 92.8% [95% CI, 89.5%-95.0%], p = 0.006 and 83.8% [95% CI, 69.9%-91.7%], p = 0.012). Estimated survival improved from baseline with each year of survival for all grades of metastatic chondrosarcoma. Conditional survival estimates for Grade 3 axial tumors failed to improve from baseline to 5 years after diagnosis (52.9% versus 70.2%, p > 0.05) compared with Grade 3 extremity tumors at baseline and 5 years after diagnosis (58.1% versus 95.8%, p < 0.0001) The 20-year conditional survival estimates reveal that a cancer-specific risk of mortality exists even 10 years after diagnosis, suggesting that although the conditional survival increases considerably over time, it cannot be considered cured. CONCLUSIONS: The 5-year conditional survival estimate for patients with chondrosarcoma improved with each additional year of survival regardless of grade, site, age, or use of radiation. At 10 years after diagnosis, deaths attributable to cancer were still present, and patients should be aware of this small long-term risk. LEVEL OF EVIDENCE: Level II, prognostic study. See the Instructions for Authors for a complete description of levels of evidence.

Is Perioperative Radiotherapy Effective in Preventing Local Recurrence in Myxofibrosarcoma?

Background: Myxofibrosarcoma (MFS) is a rare type of soft tissue sarcoma that is locally aggressive and has a high risk of recurrence. The effectiveness of perioperative radiotherapy (RT) in preventing local recurrence (LR) of MFS remains uncertain. This retrospective study aimed to evaluate the impact of perioperative radiotherapy on local recurrence in patients with MFS. Methods: A total of 75 patients diagnosed with MFS and treated at a single institution were included in the study. Patient data, including demographics, tumor characteristics, and treatment variables, were collected from electronic medical records. The primary endpoint was the occurrence of local recurrence. Results: Among the patients, 25/75 (33.3%) received radiation therapy, while 50/75 (66.7%) did not. Local recurrence in the radiated group was 28% (7/25) compared to 36% (18/50) in the non-irradiated group (p = 0.20). The LR rate trended higher in patients who received RT postoperatively (adjuvant) (6/12, 50%) than preoperatively (neoadjuvant) (1/13, 7.6%) (p = 0.124). Of the 54 patients with negative margins, the local recurrence rate was lower in the radiated group (1/12, 8.33) than the non-irradiated group (9/36, 25%) (p = 0.034). A subgroup analysis based on tumor grade did not reveal any significant differences in recurrence rates between the radiated and non-irradiated groups. Furthermore, there was no significant difference in recurrence rates between the irradiated and non-irradiated groups at the one-year (p = 0.32), two-year (p = 0.24), and five-year (p = 0.32) follow-up marks. Conclusion: Although radiotherapy demonstrated a trend toward reduction in recurrence rates in patients with MFS in this study, the observed difference did not reach statistical significance. Neoadjuvant radiation appears to be more effective than adjuvant radiation. However, there was a significant reduction in recurrence in patients with negative margins who received radiation demonstrating that effective surgical resection continues to be the most important intervention in patients with myxofibrosarcoma. Level of Evidence: III.

Superoxide Dismutase Mimetic Avasopasem Manganese Enhances Radiation Therapy Effectiveness in Soft Tissue Sarcomas and Accelerates Wound Healing.

Soft tissue sarcomas (STSs) are mesenchymal malignant lesions that develop in soft tissues. Despite current treatments, including radiation therapy (RT) and surgery, STSs can be associated with poor patient outcomes and metastatic recurrences. Neoadjuvant radiation therapy (nRT), while effective, is often accompanied by severe postoperative wound healing complications due to damage to the surrounding normal tissues. Thus, there is a need to develop therapeutic approaches to reduce nRT toxicities. Avasopasem manganese (AVA) is a selective superoxide dismutase mimetic that protects against IR-induced oral mucositis and lung fibrosis. We tested the efficacy of AVA in enhancing RT in STSs and in promoting wound healing. Using colony formation assays and alkaline comet assays, we report that AVA selectively enhanced the STS (liposarcoma, fibrosarcoma, leiomyosarcoma, and MPNST) cellular response to radiation compared to normal dermal fibroblasts (NDFs). AVA is believed to selectively enhance radiation therapy by targeting differential hydrogen peroxide clearance in tumor cells compared to non-malignant cells. STS cells demonstrated increased catalase protein levels and activity compared to normal fibroblasts. Additionally, NDFs showed significantly higher levels of GPx1 activity compared to STSs. The depletion of glutathione using buthionine sulfoximine (BSO) sensitized the NDF cells to AVA, suggesting that GPx1 may, in part, facilitate the selective toxicity of AVA. Finally, AVA significantly accelerated wound closure in a murine model of wound healing post RT. Our data suggest that AVA may be a promising combination strategy for nRT therapy in STSs.