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.

Neoadjuvant pazopanib in nonrhabdomyosarcoma soft tissue sarcomas (ARST1321): A report of major wound complications from the Children's Oncology Group and NRG Oncology.

BACKGROUND AND OBJECTIVES: The impact upon wound healing of targeted molecular therapies, when incorporated into neoadjuvant therapy of soft tissue sarcoma, is largely unknown. Here, we describe wound complications following addition of pazopanib, a tyrosine kinase inhibitor (TKI), to neoadjuvant radiotherapy (RT) +/- chemotherapy for soft tissue sarcoma. METHODS: Wound complications were evaluated on dose-finding and randomized arms of ARST1321, a phase II/III study incorporating neoadjuvant RT, +/- pazopanib, +/- ifosfamide/doxorubicin (ID) for sarcoma therapy. RESULTS: Of 85 evaluable patients, 35 (41%) experienced postoperative wound complications. Most (57%) were grade III. Randomization to pazopanib + RT + ID carried a 50% wound complication rate (17/34, with 47% grade III), compared to 22% (5/23) with ID + RT alone. In nonchemotherapy study arms, pazopanib + RT resulted in a 59% wound complication rate versus 25% for those receiving RT alone. Grade III wound complications occurred among 26% (15/58) of all patients receiving pazopanib. Wound complications occurred a median of 35 days postoperatively. Some occurred following diagnostic biopsies and at remote surgical sites. CONCLUSION: The addition of pazopanib to neoadjuvant chemotherapy and RT resulted in a higher wound complication rate following therapy of soft tissue sarcoma. The rate of grade III complications remained comparable to that reported in contemporary literature.

Utility of 45S5 Bioactive Glass As Bone Graft Substitute for Cavitary Defects in Pediatric Bone Tumors: A Preliminary Study.

BACKGROUND: Bioactive glass has become an increasingly used treatment of cavitary bone defects in a number of orthopaedic applications. The purpose of this study was to evaluate the clinical and radiographic outcomes of bioactive glass used for benign cavitary pediatric bone tumors. A specific focus was on radiographic filling of defects and occurrence of complications by tumor class. METHODS: A single institution retrospective study was performed, which entailed review of the clinical and radiographic data of 21 patients who underwent surgical curettage and grafting of benign or low-grade malignant bone tumors from 2018 to 2020. In all the cases, 45S5 bioactive glass (Fibergraft; Prosidyan, New Providence, NJ) was used to fill the bone defects. For each patient, data on demographic, preoperative diagnosis, defect size, time to mobilization, radiographic filling grade, pain, and complications were obtained. The Wilcoxon-Mann-Whitney test and Kaplan-Meier survival analysis were used for comparisons between tumor classes. RESULTS: In the 21 patients, 11 bone tumors were latent or active (class 1) and 10 were aggressive (class 2). The mean age was 13.0±3.7 years, 6 (28.6%) were female, and the median and interquartile range for initial tumor size were 18.8 (5.8 to 50.6) cm 3 . Tumors that were class 2 had significantly more complications with bioactive glass use compared with class 1 tumors [0 vs. 1 (0 to 1), P =0.040]. The time of persistent fill grade 1 or 2 defects up to final follow-up was less in class 1 versus class 2 lesions ( P =0.048). CONCLUSIONS: Bioactive glass agents have utility for treating a broad variety of pediatric bone tumors after curettage. However, focusing these agents' use in treating latent or active subtypes of bone tumors may be ideal in minimizing complications and time to higher fill grade. LEVEL OF EVIDENCE: Level III - Therapeutic.

Nerve transfers to restore femoral nerve function following oncologic nerve resection.

INTRODUCTION: Advances in the care of soft-tissue tumors, including imaging capabilities and adjuvant radiation therapy, have broadened the indications and opportunities to pursue surgical limb salvage. However, peripheral nerve involvement and femoral nerve resection can still result in devastating functional outcomes. Nerve transfers offer a versatile solution to restore nerve function following tumor resection. METHODS: Two cases were identified by retrospective review. Patient and disease characteristics were gathered. Preoperative and postoperative motor function were assessed using the Medical Research Council Muscle Scale. Patient-reported pain levels were assessed using the numeric rating scale. RESULTS: Nerve transfers from the obturator and sciatic nerve were employed to restore knee extension. Follow up for Case 1 was 24 months, 8 months for Case 2. In both patients, knee extension and stabilization of gait without bracing was restored. Patient also demonstrated 0/10 pain (an average improvement of 5 points) with decreased neuromodulator and pain medication use. CONCLUSION: Nerve transfers can restore function and provide pain control benefits and ideally are performed at the time of tumor extirpation. This collaboration between oncologic and nerve surgeons will ultimately result in improved functional recovery and patient outcomes.

Has the Affordable Care Act Been Associated with Increased Insurance Coverage and Early-stage Diagnoses of Bone and Soft-tissue Sarcomas in Adults?

BACKGROUND: Treatment of bone and soft-tissue sarcomas can be costly, and therefore, it is not surprising that insurance status of patients is a prognostic factor in determining overall survival. Furthermore, uninsured individuals with suspected bone and/or soft-tissue masses routinely encounter difficulty in obtaining access to basic healthcare (such as office visits, radiology scans), and therefore are more likely to be diagnosed with later stages at presentation. The Patient Protection and Affordable Care Act (ACA) mandate of 2010 aimed to increase access to care for uninsured individuals by launching initiatives, such as expanding Medicaid eligibility, subsidizing private insurance, and developing statewide mandates requiring individuals to have a prescribed minimum level of health insurance. Although prior reports have demonstrated that the ACA increased both coverage and the proportion of early-stage diagnoses among patients with common cancers (including breast, colon, prostate, and lung), it is unknown whether similar improvements have occurred for patients with bone and soft-tissue sarcomas. Understanding changes in insurance coverages and stage at diagnosis of patients with bone and soft-tissue sarcomas would be paramount in establishing policies that will ensure orthopaedic cancer care is made equitable and accessible to all. QUESTIONS/PURPOSES: (1) Has the introduction of the ACA been associated with changes in insurance coverage for adult patients with newly diagnosed bone and soft-tissue sarcomas? (2) Did the introduction of health reforms under the ACA lead to an increased proportion of sarcoma diagnoses occurring at earlier disease stages? METHODS: The 2007 to 2015 Surveillance, Epidemiology and End Results database was queried using International Classification of Diseases for Oncology codes for primary malignant bone tumors of the upper and lower extremity (C40.0 to C40.3), unspecified or other overlapping bone, articular cartilage, and joint and/or ribs, sternum, or clavicle (C40.8 to C40.9, C41.3, and C41.8 to C41.9), vertebral column (C41.2), pelvis (C41.4, C41.8, and C41.9), and soft-tissue sarcomas of the upper or lower extremity and/or pelvis (C49.1, C49.2, and C49.5). A total of 15,287 patients with newly diagnosed cancers were included, of which 3647 (24%) were malignant bone tumors and 11,640 (76%) were soft-tissue sarcomas. The study sample was divided into three cohorts according to specified time periods: pre-ACA from 2007 to 2010 (6537 patients), pre-Medicaid expansion from 2011 to 2013 (5076 patients), and post-Medicaid expansion from 2014 to 2015 (3674 patients). The Pearson chi square tests were used to assess for changes in the proportion of Medicaid and uninsured patients across the specified time periods: pre-ACA, pre-expansion and post-expansion. A differences-in-differences analysis was also performed to assess changes in insurance coverage for Medicaid and uninsured patients among states that chose to expand Medicaid coverage in 2014 under the ACA's provision versus those who opted out of Medicaid expansion. Since the database switched to using the American Joint Commission on Cancer (AJCC) 7th edition staging system in 2010, linear regression using data only from 2010 to 2015 was performed that assessed changes in cancer stage at diagnosis from 2010 to 2015 alone. After stratifying by cancer type (bone or soft-tissue sarcoma), Pearson chi square tests were used to assess for changes in the proportion of patients who were diagnosed with early, late, and unknown stage at presentation before Medicaid expansion (2011-2013) and after Medicaid expansion (2014-2015) among states that chose to expand versus those who did not. RESULTS: After stratifying by time cohorts: pre-ACA (2007 to 2010), pre-expansion (2011 to 2013) and post-expansion (2014 to 2015), we observed that the most dramatic changes occurred after Medicaid eligibility was expanded (2014 onwards), with Medicaid proportions increasing from 12% (pre-expansion, 2011 to 2013) to 14% (post-expansion, 2014 to 2015) (p < 0.001) and uninsured proportions decreasing from 5% (pre-expansion, 2011 to 2013) to 3% (post-expansion, 2014 to 2015) (p < 0.001). A differences-in-differences analysis that assessed the effect of Medicaid expansion showed that expanded states had an increase in the proportion of Medicaid patients compared with non-expanded states, (3.6% [95% confidence interval 0.4 to 6.8]; p = 0.03) from 2014 onwards. For the entire study sample, the proportion of early-stage diagnoses (I/II) increased from 56% (939 of 1667) in 2010 to 62% (1137 of 1840) in 2015 (p = 0.003). Similarly, the proportion of unknown stage diagnoses decreased from 11% (188 of 1667) in 2010 to 7% (128 of 1840) in 2015 (p = 0.002). There was no change in proportion of late-stage diagnoses (III/IV) from 32% (540 of 1667) in 2010 to 31% (575 of 1840) in 2015 (p = 0.13). CONCLUSION: Access to cancer care for patients with primary bone or soft-tissue sarcomas improved after the ACA was introduced, as evidenced by a decrease in the proportion of uninsured patients and corresponding increase in Medicaid coverage. Improvements in coverage were most significant among states that adopted the Medicaid expansion of 2014. Furthermore, we observed an increasing proportion of early-stage diagnoses after the ACA was implemented. The findings support the preservation of the ACA to ensure cancer care is equitable and accessible to all vulnerable patient populations. LEVEL OF EVIDENCE: Level III, therapeutic study.

Has the Volume and Variability of Procedures Reported by Fellows in ACGME-accredited Musculoskeletal Oncology Fellowship Programs Changed Over Time?

BACKGROUND: There has been a considerable rise in the number of musculoskeletal/orthopaedic oncology fellowships and subsequently, orthopaedic oncologists, in the nation. National societies have been concerned that the increasing number of orthopaedic oncologists, coupled with a limited number of patients with bone and soft-tissue sarcomas in the country, may have led to an unintended impact on the training spectrum and/or exposure of orthopaedic oncology fellows-in-training over time. Fellows who are unable to gain exposure by operating on varied cancer presentations during training may be less confident in dealing with a wide array of patients in their practice. Despite these concerns, the volume and variability of procedures performed by fellows-in-training remains unknown. Understanding these parameters will be helpful in establishing policies for standardizing training of prospective fellows to ensure they are well-equipped to care for patients with bone and/or soft-tissue sarcomas in the beginning of their career. QUESTIONS/PURPOSES: (1) Has the median surgical procedure volume per fellow changed over time? (2) How much variability in procedural volume exists between fellows, based on the most recent (2017) Accreditation Council on Graduate Medical Education (ACGME) procedure log data? (3) What proportion of fellows are meeting the minimum procedure volume thresholds, as recommended by the Musculoskeletal Tumor Society (MSTS)? METHODS: The 2010 to 2017 ACGME fellowship procedure logs for musculoskeletal oncology fellowships were retrieved from the council's official website. All fellows enrolled in ACGME-accredited fellowships are mandated to complete case logs before graduation. This study did not include operative procedures performed by fellows in nonACGME-approved fellowship programs. The 2010 to 2016 anatomic site-based procedure log data were used to evaluate fellows' overall and location-specific median operative or patient volume, using descriptive statistics. Linear regression analyses were used to assess changes in the median procedure volume over time. The 2017 categorized procedure log data were used to assess variability in procedure volume between the lowest (10th percentile) and highest (90th percentile) of all fellows. Using 2017 procedure logs, we compared the minimum procedure volume standards, as defined by the MSTS, against the number of procedures performed by fellows across the 10th, 30th, 50th (median), 70th, and 90th percentiles. RESULTS: There was no change in the median (range) procedural volume per fellow from 2010 (292 procedures [131 to 634]) to 2017 (312 procedures [174 to 479]; p = 0.58). Based on 2017 categorized procedure log data, there was considerable variability in procedural volume between the lowest (10th) percentile and highest (90th) percentile of fellows across programs: pediatric oncologic procedures (10-fold difference), surgical management of complications from limb-salvage surgery (sevenfold difference), soft-tissue resections or reconstructions (fourfold difference), bone sarcoma resections or limb-salvage surgery (fourfold difference), and spine, sacrum, and pelvis procedures (threefold difference). A fair proportion of fellows did not meet the minimum procedure volume standards, as recommended by the MSTS across certain categories. For the spine and pelvis (minimum = 10 procedures), fellows in the lowest 10th percentile performed only six procedures. For patients with bone sarcomas or limb salvage (minimum = 20 procedures), fellows in the lowest 10th percentile performed only 14 procedures. For pediatric patients with oncologic conditions (minimum = 15 procedures), fellows in the 50th percentile (13 procedures) and below failed to meet the thresholds. For surgical management of complications from limb-salvage procedures (minimum = five procedures), fellows in the lowest 10th percentile performed only three procedures. CONCLUSION: Although we were encouraged to observe that the median number of procedures performed by musculoskeletal oncology fellows over this time has not changed, we observed wide variability in the procedure volume among fellows for pediatric sarcomas, soft-tissue resection and reconstruction, limb salvage procedures, and spine procedures. We do not know how this compares with fellows trained in nonaccredited fellowship programs. CLINICAL RELEVANCE: Although we recognize that the education of fellows entails much more than performing operations, national societies have recognized a need to bring about more uniformity or standardization of training in musculoskeletal oncology. Limiting the number of orthopaedic oncology fellowships to high-volume institutions, expanding the training time period, and/or introducing subspecialty certification may be possible avenues through which standardization of training can be defined.

What Is the Value of Undergoing Surgery for Spinal Metastases at Dedicated Cancer Centers?

BACKGROUND: The Alliance of Dedicated Cancer Centers is an organization of 11 leading cancer institutions and affiliated hospitals that are exempt from the Medicare prospective system hospital reimbursement policies. Because of their focus on cancer care and participation in innovative cancer treatment methods and protocols, these hospitals are reimbursed based on their actual billings. The perceived lack of incentive to meet a predetermined target price and reduce costs has spurred criticism of the value of cancer care at these institutions. The rationale of our study was to better understand whether dedicated cancer centers (DCCs) deliver high-value care for patients undergoing surgical treatment of spinal metastases. QUESTION/PURPOSE: Is there a difference in 90-day complications and reimbursements between patients undergoing surgical treatment (decompression or fusion) for spinal metastases at DCCs and those treated at nonDCC hospitals? METHODS: The 2005 to 2014 100% Medicare Standard Analytical Files database was queried using ICD-9 procedure and diagnosis codes to identify patients undergoing decompression (03.0, 03.09, and 03.4) and/or fusion (81.0X) for spinal metastases (198.5). The database does not allow us to exclude the possibility that some patients were treated with fusion for stabilization of the spine without decompression, although this is likely an uncommon event. Patients undergoing vertebroplasty or kyphoplasty for metastatic disease were excluded. The Medicare hospital provider identification numbers were used to identify the 11 DCCs. The study cohort was categorized into two groups: DCCs and nonDCCs. Although spinal metastases are known to occur among nonMedicare and younger patients, the payment policies of these DCCs are only applicable to Medicare beneficiaries. Therefore, to keep the study objective relevant to current policy and value-based discussions, we performed the analysis using the Medicare dataset. After applying the inclusion and exclusion criteria, we included 17,776 patients in the study, 6% (1138 of 17,776) of whom underwent surgery at one of the 11 DCCs. Compared with the nonDCC group, DCC group hospitals operated on a younger patient population and on more patients with primary renal cancers. In addition, DCCs were more likely to be high-volume facilities with National Cancer Institute designations and have a voluntary or government ownership model. Patients undergoing surgery for spinal metastases at DCCs were more likely to have spinal decompression with fusion than those at nonDCCs (40% versus 22%; p < 0.001) and had a greater length and extent of fusion (at least four levels of fusion; 34% versus 29%; p = 0.001). Patients at DCCs were also more likely than those at nonDCCs to receive postoperative adjunct treatments such as radiation (16% versus 13.5%; p = 0.008) and chemotherapy (17% versus 9%; p < 0.001), although this difference is small and we do not know if this meets a minimum clinically important difference. To account for differences in patients presenting at both types of facilities, multivariate logistic regression mixed-model analyses were used to compare rates of 90-day complications and 90-day mortality between DCC and nonDCC hospitals. Controls were implemented for baseline clinical characteristics, procedural factors, and hospital-level factors (such as random effects). Generalized linear regression mixed-modeling was used to evaluate differences in total 90-day reimbursements between DCCs and nonDCCs. RESULTS: After adjusting for differences in baseline demographics, procedural factors, and hospital-level factors, patients undergoing surgery at DCCs had lower odds of experiencing sepsis (6.5% versus 10%; odds ratio 0.54 [95% confidence interval 0.40 to 0.74]; p < 0.001), urinary tract infections (19% versus 28%; OR 0.61 [95% CI 0.50 to 0.74]; p < 0.001), renal complications (9% versus 13%; OR 0.55 [95% CI 0.42 to 0.72]; p < 0.001), emergency department visits (27% versus 31%; OR 0.78 [95% CI 0.64 to 0.93]; p = 0.01), and mortality (39% versus 49%; OR 0.75 [95% CI 0.62 to 0.89]; p = 0.001) within 90 days of the procedure compared with patients treated at nonDCCs. Undergoing surgery at a DCC (90-day reimbursement of USD 54,588 ± USD 42,914) compared with nonDCCs (90-day reimbursement of USD 49,454 ± USD 38,174) was also associated with reduced 90-day risk-adjusted reimbursements (USD -14,802 [standard error 1362] ; p < 0.001). CONCLUSION: Based on our findings, it appears that DCCs offer high-value care, as evidenced by lower complication rates and reduced reimbursements after surgery for spinal metastases. A better understanding of the processes of care adopted at these institutions is needed so that additional cancer centers may also be able to deliver similar care for patients with metastatic spine disease. LEVEL OF EVIDENCE: Level III, therapeutic study.

Is Grit Associated with Burnout and Well-being in Orthopaedic Resident and Faculty Physicians? A Multi-institution Longitudinal Study Across Training Levels.

BACKGROUND: Grit has been defined as "perseverance and passion for long-term goals" and is characterized by maintaining focus and motivation toward a challenging ambition despite setbacks. There are limited data on the impact of grit on burnout and psychologic well-being in orthopaedic surgery, as well as on which factors may be associated with these variables. QUESTIONS/PURPOSES: (1) Is grit inversely correlated with burnout in orthopaedic resident and faculty physicians? (2) Is grit positively correlated with psychologic well-being in orthopaedic resident and faculty physicians? (3) Which demographic characteristics are associated with grit in orthopaedic resident and faculty physicians? (4) Which demographic characteristics are associated with burnout and psychologic well-being in orthopaedic resident and faculty physicians? METHODS: This study was an institutional review board-approved interim analysis from the first year of a 5-year longitudinal study of grit, burnout, and psychologic well-being in order to assess baseline relationships between these variables before analyzing how they may change over time. Orthopaedic residents, fellows, and faculty from 14 academic medical centers were enrolled, and 30% (335 of 1129) responded. We analyzed for the potential of response bias and found no important differences between sites in low versus high response rates, nor between early and late responders. Participants completed an email-based survey consisting of the Duckworth Short Grit Scale, Maslach Burnout Inventory-Human Services (Medical Personnel) Survey, and Dupuy Psychological Well-being Index. The Short Grit Scale has been validated with regard to internal consistency, consensual and predictive validity, and test-retest stability. The Psychological Well-being Index has similarly been validated with regard to reliability, test-retest stability, and internal consistency, and the Maslach Burnout Inventory has been validated with regard to internal consistency, reliability, test-retest stability, and convergent validity. The survey also obtained basic demographic information such as survey participants' age, gender, race, ethnicity, marital status, current year of training or year in practice (as applicable), and region of practice. The studied population consisted of 166 faculty, 150 residents, and 19 fellows. Beyond the expected age differences between sub-populations, the fellow population had a higher proportion of women than the faculty and resident populations did. Pearson correlations and standardized ß coefficients were used to assess the relationships of grit, burnout, psychologic well-being, and continuous participant characteristics. RESULTS: We found moderate, negative relationships between grit and emotional exhaustion (r = -0.30; 95% CI -0.38 to -0.21; p < 0.001), depersonalization (r = -0.34; 95% CI -0.44 to -0.23; p < 0.001), and the overall burnout score (r = -0.39; 95% CI -0.48 to -0.31; p < 0.001). The results also showed a positive correlation between grit and personal accomplishment (r = 0.39; 95% CI 0.29 to 0.48; p < 0.001). We also found a moderate, positive relationship between grit and psychologic well-being (r = 0.39; 95% CI 0.30 to 0.49; p < 0.001). Orthopaedic surgeons with 21 years or more of practice had higher grit scores than physicians with 10 to 20 years of practice. Orthopaedic surgeons in practice for 21 years or more also had lower burnout scores than those in practice for 10 to 20 years. Married physicians had higher psychologic well-being than unmarried physicians did. CONCLUSION: Among orthopaedic residents, fellows, and faculty, grit is inversely related to burnout, with lower scores for emotional exhaustion and depersonalization and higher scores for personal accomplishment as grit increases. CLINICAL RELEVANCE: The results suggest that grit could be targeted as an intervention for reducing burnout and promoting psychologic well-being among orthopaedic surgeons. Other research has suggested that grit is influenced by internal characteristics, life experiences, and the external environment, suggesting that there is potential to increase one's grit. Residency programs and faculty development initiatives might consider measuring grit to assess for the risk of burnout, as well as offering curricula or training to promote this psychologic characteristic.

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.

Pathological response in children and adults with large unresected intermediate-grade or high-grade soft tissue sarcoma receiving preoperative chemoradiotherapy with or without pazopanib (ARST1321): a multicentre, randomised, open-label, phase 2 trial.

BACKGROUND: Outcomes for children and adults with advanced soft tissue sarcoma are poor with traditional therapy. We investigated whether the addition of pazopanib to preoperative chemoradiotherapy would improve pathological near complete response rate compared with chemoradiotherapy alone. METHODS: In this joint Children's Oncology Group and NRG Oncology multicentre, randomised, open-label, phase 2 trial, we enrolled eligible adults (aged ≥18 years) and children (aged between 2 and <18 years) from 57 hospitals in the USA and Canada with unresected, newly diagnosed trunk or extremity chemotherapy-sensitive soft tissue sarcoma, which were larger than 5 cm in diameter and of intermediate or high grade. Eligible patients had Lansky (if aged ≤16 years) or Karnofsky (if aged >16 years) performance status score of at least 70. Patients received ifosfamide (2·5 g/m2 per dose intravenously on days 1-3 with mesna) and doxorubicin (37·5 mg/m2 per dose intravenously on days 1-2) with 45 Gy preoperative radiotherapy, followed by surgical resection at week 13. Patients were randomly assigned (1:1) using a web-based system, in an unmasked manner, to receive oral pazopanib (if patients <18 years 350 mg/m2 once daily; if patients ≥18 years 600 mg once daily) or not (control group), with pazopanib not given immediately before or after surgery at week 13. The study projected 100 randomly assigned patients were needed to show an improvement in the number of participants with a 90% or higher pathological response at week 13 from 40% to 60%. Analysis was done per protocol. This study has completed accrual and is registered with ClinicalTrials.gov, NCT02180867. FINDINGS: Between July 7, 2014, and Oct 1, 2018, 81 eligible patients were enrolled and randomly assigned to the pazopanib group (n=42) or the control group (n=39). At the planned second interim analysis with 42 evaluable patients and a median follow-up of 0·8 years (IQR 0·3-1·6) in the pazopanib group and 1 year (0·3-1·6) in the control group, the number of patients with a 90% pathological response or higher was 14 (58%) of 24 patients in the pazopanib group and four (22%) of 18 patients in the control group, with a between-group difference in the number of 90% or higher pathological response of 36·1% (83·8% CI 16·5-55·8). On the basis of an interim analysis significance level of 0·081 (overall one-sided significance level of 0·20, power of 0·80, and O'Brien-Fleming-type cumulative error spending function), the 83·8% CI for response difference was between 16·5% and 55·8% and thus excluded 0. The improvement in pathological response rate with the addition of pazopanib crossed the predetermined boundary and enrolment was stopped. The most common grade 3-4 adverse events were leukopenia (16 [43%] of 37 patients), neutropenia (15 [41%]), and febrile neutropenia (15 [41%]) in the pazopanib group, and neutropenia (three [9%] of 35 patients) and febrile neutropenia (three [9%]) in the control group. 22 (59%) of 37 patients in the pazopanib group had a pazopanib-related serious adverse event. Paediatric and adult patients had a similar number of grade 3 and 4 toxicity. There were seven deaths (three in the pazopanib group and four in the control group), none of which were treatment related. INTERPRETATION: In this presumed first prospective trial of soft tissue sarcoma spanning nearly the entire age spectrum, adding pazopanib to neoadjuvant chemoradiotherapy improved the rate of pathological near complete response, suggesting that this is a highly active and feasible combination in children and adults with advanced soft tissue sarcoma. The comparison of survival outcomes requires longer follow-up. FUNDING: National Institutes of Health, St Baldrick's Foundation, Seattle Children's Foundation.

Malignant fibrous histiocytoma of bone: A survival analysis from the National Cancer Database.

BACKGROUND AND OBJECTIVES: Malignant fibrous histiocytoma (MFH) of bone, now known as undifferentiated pleomorphic sarcoma of bone, is a rare neoplasm that accounts for less than 2% of all primary malignant bone tumors. The objective of the current study was to evaluate prognosis and survival for MFH of bone. METHODS: The 2004 to 2016 National Cancer Database was queried to identify patients with a primary MFH of bone. Kaplan-Meier survival and Cox regression analyses were used to analyze overall survival and risk factors associated with overall mortality. RESULTS: The overall 5-year and 10-year survival rates were 38.3% and 30.5%, respectively. Increasing stage and metastatic disease at presentation were associated with poor overall survival (P < .001). Patients aged 18 to 50 years (hazard ratio [HR], 0.51), 51 to 75 years (HR, 0.61), and those undergoing surgery (HR, 0.39) had improved survival. Having Medicare insurance (HR, 1.48), residing in a low educated area (HR, 2.56), and positive surgical margins (HR, 1.80) were associated with poor survival. CONCLUSIONS: The overall prognosis of MFH of bone is poor with a reported 5-year survival rate of 38.3%. Undergoing surgery and younger age were associated with a better prognosis. Older age, having Medicare insurance, and positive surgical margins were predictors of mortality.

Is Treatment at a High-volume Center Associated with an Improved Survival for Primary Malignant Bone Tumors?

BACKGROUND: Centralization of cancer care to high-volume facilities has been shown to improve the overall survival of patients with soft-tissue sarcomas. Current evidence regarding the impact of increased hospital volume on treatment patterns and survival rates for patients with primary malignant bone tumors remains limited. Understanding the facility volume-outcome relationship for primary malignant bone tumors will further discussion on ways to promote delivery of quality cancer care across the nation. QUESTIONS/PURPOSES: (1) Is there a difference in overall survival for patients with primary malignant bone tumors undergoing treatment at a high-volume facility (at least 20 patients per year) versus those treated at a low-volume facility (less than 20 patients per year)? (2) Do surgical treatment patterns (limb-salvage versus amputation) and margin status (positive versus negative) vary between high-volume and low-volume facilities? METHODS: The 2004 to 2015 National Cancer Database was queried using International Classification of Disease for Oncology topographical codes to identify patients undergoing treatment (surgery, chemotherapy, and/or radiation therapy) for primary malignant bone tumors of the extremities (C40.0-C40.3, C40.8, and C40.9) or pelvis (C41.4). Histologic codes were used to group the tumors into the following categories: osteosarcomas, Ewing's sarcomas, chondrosarcomas, chordomas, and other or unspecified. Patients who did not receive any treatment (surgery, chemotherapy, and/or radiotherapy) at the reporting facility were excluded from the study. Facility volume was calculated based on the average number of patients per year for the entire study period. A preliminary stratified Cox regression model was used to identify evidence-based thresholds or cutoffs for high-volume and low-volume facilities, while adjusting for differences in patient, tumor, and treatment characteristics. We identified high-volume facilities as those treating at least 20 patients per year and low-volume facilities as those treating fewer than 20 patients per year. A Kaplan-Meier survival analysis was used to report overall unadjusted 5-year survival rates at high-volume and low-volume facilities. Multivariate Cox regression analyses were used to assess whether undergoing treatment at a high-volume facility was associated with a lower risk of overall mortality, after controlling for differences in baseline demographics, tumor presentation, and treatment characteristics. For patients undergoing surgery, multivariate regression models were used to evaluate whether patients receiving care in a high-volume facility were more likely to receive resections with limb salvage surgery than to receive amputation and whether facility volume was associated with a patient's likelihood of having a positive or negative surgical margin. RESULTS: A total of 14,039 patients were included, 15% (2115) of whom underwent treatment in a high-volume facility. Patients undergoing treatment at a high-volume facility were more likely to be white, have tumors involving the pelvis, have larger tumor sizes, and have a higher tumor grade at presentation than those undergoing treatment at a low-volume facility. Unadjusted 5-year overall survival rates were greater for high-volume facilities than for low-volume facilities (65% versus 61%; p = 0.003). After controlling for differences in patient demographics, tumor characteristics (including histologic type, grade, stage, size, and location) and treatment factors, we found that patients treated at high-volume facilities had a slightly lower overall mortality risk than those treated at low-volume facilities (hazard ratio 0.85 [95% CI 0.77 to 0.93]; p < 0.001). Patients treated at high-volume facilities were also slightly more likely to undergo resection with limb-salvage surgery to than to undergo amputation (odds ratio 1.34 [95% CI 1.14 to 1.59]; p = 0.001). Patients undergoing surgical treatment at high-volume facilities also had a lower odds of having positive resection margins than those undergoing treatment at low-volume facilities (OR 0.56 [95% CI 0.44 to 0.72]; p < 0.001). CONCLUSIONS: Patients undergoing treatment for primary malignant bone tumors at high-volume facilities experience a slightly better overall survival than those receiving treatment at low-volume facilities. Further research questioning the value of care at high-volume facilities is required before sweeping changes in regionalization can be considered. LEVEL OF EVIDENCE: Level III, therapeutic study.

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.

What Are the Costs of Hip Osteoarthritis in the Year Prior to a Total Hip Arthroplasty?

BACKGROUND: The majority of the cost analysis literature on total hip arthroplasties (THAs) has been focused around the perioperative and postoperative period, with preoperative costs being overlooked. METHODS: The Humana Administrative Claims database was used to identify Medicare Advantage (MA) and Commercial beneficiaries undergoing elective primary THAs. Preoperative healthcare resource utilization in the year prior to a THA was grouped into the following categories: office visits, X-rays, magnetic resonance imagings, computed tomography scans, intra-articular steroid and hyaluronic acid injections, physical therapy, and pain medications. Total 1-year costs and per-patient average reimbursements for each category have been reported. RESULTS: Total 1-year preoperative costs amounted to $21,022,883 (average = $512/patient) and $4,481,401 (average = $764/patient) for MA and Commercial beneficiaries, respectively. The largest proportion of total 1-year costs was accounted for by office visits (35% in Commercial; 41% in MA) followed by pain medications (28% in Commercial; 35% in MA). Conservative treatments (steroid injections, hyaluronic acid injections, physical therapy, and pain medications) alone accounted for 40%-44% of the total 1-year costs prior to a THA. A high healthcare utilization within the last 3 months prior to surgery was noted for opioids and steroid injections. CONCLUSION: On average, $500-$800/patient is spent on hip osteoarthritis-related care in the year prior to a THA. Despite their potential risks, opioids and steroid injections are often utilized in the last 3 months prior to surgery.

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.

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.

Does Surgeon Volume Affect Outcomes Following Primary Total Hip Arthroplasty? A Systematic Review.

BACKGROUND: Surgeon volume has been identified as an important factor impacting postoperative outcome in patients undergoing orthopedic surgeries. With an absence of a detailed systematic review, we sought to collate evidence on the impact of surgeon volume on postoperative outcomes in patients undergoing primary total hip arthroplasty. METHODS: PubMed (MEDLINE) and Google Scholar databases were queried for articles using the following search criteria: ("Surgeon Volume" OR "Provider Volume" OR "Volume Outcome") AND ("THA" OR "Total hip replacement" OR "THR" OR "Total hip arthroplasty"). Studies investigating total hip arthroplasty being performed for malignancy or hip fractures were excluded from the review. Twenty-eight studies were included in the final review. All studies underwent a quality appraisal using the GRADE tool. The systematic review was performed in accordance with the PRISMA guidelines. RESULTS: Increasing surgeon volume was associated with a shorter length of stay, lower costs, and lower dislocation rates. Studies showed a significant association between an increasing surgeon volume and higher odds of early-term and midterm survivorship, but not long-term survivorships. Although complications were reported and recorded differently in studies, there was a general trend toward a lower postoperative morbidity with regard to complications following surgeries by a high-volume surgeon. CONCLUSION: This systematic review shows evidence of a trend toward better postoperative outcomes with high-volume surgeons. Future prospective studies are needed to better determine long-term postoperative outcomes such as survivorship before healthcare policies such as regionalization and/or equal-access healthcare systems can be considered.

Clinical trial enrollment of adolescents and young adults with sarcoma.

More than half of all sarcomas occur in adolescents and young adults (AYAs) aged 15 to 39 years. After the publication of the AYA series in the April 1, 2016 issue of Cancer, several leaders in the field of sarcoma across disciplines gathered to discuss the status of sarcoma clinical research in AYAs. They determined that a focused effort to include the underrepresented and understudied AYA population in current and future sarcoma clinical trials is overdue. Trial enrichment for AYA-aged sarcoma patients will produce more meaningful results that better represent the disease's biology, epidemiology, and treatment environment. To address the current deficit, this commentary outlines changes believed to be necessary to expediently achieve an increase in the enrollment of AYAs in sarcoma clinical trials. Cancer 2017;123:3434-40. © 2017 American Cancer Society.

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.