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Sarcomas are rare tumors of mesenchymal origin and comprise only around 1% of adult cancers. The abundance of sarcoma histiotypes, with distinct imaging characteristics, biology, clinical behavior and treatment strategy, result in a complex disease presentation, requiring management by multidisciplinary specialized sarcoma centers. Oncologic and musculoskeletal radiology guidelines provide minimal guidance and only fragmentary information on the indications of 18F-FDG PET/CT in sarcoma. Therefore, knowledge of various phenotypes with preference for bone and lymph node metastases or higher incidence of local and distant recurrence is essential to select the appropriate diagnostic imaging tests and its interpretation. Benign and malignant soft tissue and bone tumors often share common radiographic and metabolic imaging characteristics. In addition, metastases of various histiotypes might exhibit a spectrum of atypical imaging appearances. Therefore, imaging specialists need to be aware of these variants and associated pitfalls of sarcoma imaging.

An ambiguous pathologic report can present a clinical dilemma to the treating surgeon. We describe lesions ranging from the potentially benign to the likely malignant. Correctly identifying features associated with higher-risk lesions has proven challenging given the overall good prognosis and low rate of events. An appropriate treatment plan generally requires discussion between the surgeon and an experienced dermatopathologist. When clinically indicated, additional testing may be used to further support or refute a diagnosis of melanoma. The indications for these techniques, the data to support their use, and the strengths and weakness of each are reviewed.

PURPOSE Response to programmed cell death protein 1 (PD-1) blockade is often conceptualized as resulting from reinvigoration of tumor-infiltrating lymphocytes. However, recruited antitumor immunity from the periphery may also be an important contributor to response. A detailed assessment of the response dynamics of individual metastasis could provide insight to the systemic and local features that mediate response and resistance to immunotherapy. MATERIALS AND METHODS Patients with metastatic non–small-cell lung cancer (NSCLC) or mismatch repair deficiency (MMRD) carcinoma treated with PD-1 monotherapy were evaluated independently. Absolute and percent change of each target lesion were quantified at each computed tomography scan using RECIST. Patterns of progression were predefined as systemic or mixed and were correlated with clinical outcomes. RESULTS A total of 761 individual lesions from 214 patients with NSCLC and 290 lesions from 78 patients with MMRD carcinoma were examined. Individual target lesion responses aligned with best overall response of each patient (85% NSCLC and 93% MMRD lesions responded in patients with partial response/complete response). In responding patients, timing of response was uniform (73% NSCLC and 76% MMRD lesions responded synchronously), and deeper responses were associated with prolonged progression-free survival and overall survival. By contrast, at progression, mixed progression was common (45% of NSCLC and 53% of MMRD) and associated with improved survival compared with those who experienced systemic progression (NSCLC hazard ratio [HR], 0.58; P = .001; MMRD HR, 0.40; P = .07). Organ sites had differential responses, with lymph node and liver metastasis among the most and least responsive, respectively. CONCLUSION Temporal-spatial patterns of response across individual metastases tend to be uniform, favoring the role of peripheral, clonally directed antitumor immunity as a key mediator of response to PD-1 blockade. In contrast, progression is more heterogeneous, potentially revealing the clinical importance of local features and intertumoral heterogeneity.

Purpose/Objective(s) Preoperative radiation therapy (RT) is an integral component of local control in soft tissue sarcoma (STS), but the conventional 5-week treatment course is burdensome for patients (pts). We conducted a single-institution phase 2 study of 5-day dose-equivalent preoperative RT for high-risk primary STS, which demonstrated acceptable rates of wound complications and 2-year toxicity. Here, we present results with longer follow-up, including additional pts from an expansion cohort. Materials/Methods The initial cohort accrued between April 2016 and May 2018 and included 52 pts with histologically confirmed extremity or trunk STS planning to undergo preoperative RT followed by surgery. The primary endpoint of the initial cohort was the rate of grade ≥2 radiation morbidity (fibrosis, lymphedema, or joint stiffness) at 2-years. An expansion cohort opened in October 2018 to compare wound complication rates between preoperative RT alone versus chemoRT and has enrolled an additional 47 pts. Patients received 30 Gy (RT alone) or 25 Gy (chemoRT) over 5 daily fractions to the primary tumor with standard margins. Here we report on pts with primary localized STS who completed preoperative RT and surgery in the initial and expansion cohorts (N = 79; chemoRT excluded). We assessed disease outcomes (local control, distant metastasis, and survival rates) and toxicity (grade ≥2 fibrosis, lymphedema, or joint stiffness) after minimum 2-year follow-up (N = 52). Fibrosis and joint stiffness were graded using RTOG/EORTC criteria, and lymphedema by Stern's scale. We also updated the major wound complication rate (defined per established criteria) after minimum 1-year follow up (N = 60). Results Of the 52 pts with minimum 2-year follow-up, predominant histologic subtypes included undifferentiated pleomorphic sarcoma, spindle cell sarcoma or sarcoma NOS (N = 24), myxofibrosarcoma (N = 8), and myxoid liposarcoma (N = 12). Median tumor size was 6.9 cm, and 15 pts had tumors ≥10 cm. At a median follow-up of 3 years, the local recurrence, distant metastasis and all-cause mortality rates were 6.5% (3 of 46 evaluable pts), 20.8% (10 of 48 evaluable pts), and 21.2% (11 of 52). Two of 3 pts (66%) with a local recurrence had undergone R1 resections, compared to 9 of 46 (19.5%) overall. The rate of overall grade ≥2 radiation morbidity in this same group was 13.0% (fibrosis: 5 pts, joint stiffness: 5 pts, lymphedema: 2 pts). Major wound complications were observed in 16 out of 60 (26.7%) evaluable pts. Conclusion Longer follow-up of a phase 2 study of 5-day pre-operative RT for pts with extremity/trunk STS demonstrates excellent local control. Rates of radiation fibrosis, joint stiffness and lymphedema, as well as wound complications, remain acceptable. We have also developed a web-based, interactive user interface for data visualization, which can help providers identify and understand relationships between baseline characteristics and clinical outcomes in our study.

Purpose: The purpose of this study was to evaluate 18F-FLT PET/CT as an early prognostic imaging biomarker of long-term overall survival (OS) and disease-specific survival (DSS) in soft tissue sarcoma (STS) patients treated with neoadjuvant therapy (NAT) and surgical resection. Methods: This is a 10-year follow up of a previous, single-center, single-arm, prospective clinical trial. Patients underwent 18F-FLT PET/CT prior to treatment (PET1) and after NAT (PET2). Post-treatment pathology specimens were assessed for tumor necrosis / fibrosis as well as Ki-67 and TK1 expression. Maximally selected cut-offs for PET and histopathologic factors were applied. Survival was calculated from the date of subject consent to the date of death or last follow-up. Results: The study population consisted of 26 patients who underwent PET1, 16/26 primary STS underwent PET2. Thirteen deaths occurred during a median follow up period of 104 months. In the overall cohort, OS was longer in patients with low versus high PET1 tumor SUVmax (dichotomized by SUVmax ≥ 8.5 vs. < 8.5; not yet reached vs. 49.7 months; P = 0.0064). DSS showed a trend toward significance (P = 0.096). In a sub-analysis of primary STS, DSS was significantly longer in patients with low versus high PET1 tumor SUVmax (dichotomized by SUVmax ≥ 8 vs < 8; P = 0.0034). There were no significant 18F-FLT PET response thresholds corresponding to DSS or OS following NAT at PET2. Conclusion: 18F-FLT PET may serve as prognostic baseline imaging biomarker for DSS in patients with primary STS.

Background: BO-112 is a double stranded synthetic RNA formulated with polyethyleneimine. By mimicking a viral infection, it mobilizes the immune system, including activation of dendritic cells, CD8 T-cell infiltration, induction of interferons, and enhancement of immunogenic cell death. Intratumoral (IT) BO-112 has been tested both alone and in combination with anti-PD-1 therapies in a phase I trial (NCT02828098), which showed an overall response rate (ORR) of 11% and disease control rate (DCR) of 46% in patients with multiple tumor types and a tolerable safety profile. While anti-PD1 therapies have shown promise in select subtypes of soft tissue sarcoma (STS), their overall efficacy in STS has been limited. We hypothesize that BO-112, in combination with radiotherapy (RT), may reverse resistance to anti-PD1 therapy in a subset of patients with STS. Methods: This is an exploratory phase I study of IT BO-112 in combination with nivolumab in patients with STS planning to undergo neoadjuvant RT (NCT04420975) and surgery. BO-112 at a dose of 1 mg will be administered intratumorally on days 1, 8 and 15; nivolumab 240 mg will be administered intravenously on days 8 and 22. Patients will receive 5 fractions of neoadjuvant RT between day 8 and 12, followed by surgical resection between days 26 and 50. Twenty patients with newly diagnosed high grade histologically confirmed STS of the extremity, trunk or retroperitoneum amenable for IT injection will be included. Allowed histological subtypes are undifferentiated pleomorphic sarcoma, myxofibrosarcoma, leiomyosarcoma, dedifferentiated liposarcoma and synovial sarcoma.The primary objective is to explore the safety of BO-112 in combination with nivolumab in patients undergoing preoperative RT. The study includes stopping rules based on the frequency of dose limiting toxicities. As an exploratory single arm pilot study results will be reported using purely descriptive statistics. Tumor and blood specimens collected at baseline, at each IT BO-112 injection, and surgery will allow evaluation of the dynamic changes in tumor immune infiltration, T cell receptor repertoire, and tumor necrosis. These dynamic changes, along with putative biomarkers, such as baseline tumor mutational load, copy number alterations, tumor immune composition, tumor and immune gene expression signatures, and PD-L1 expression, will be related to individual subject tumor responses. The 2-year rate of local recurrence and distant metastasis will also be assessed. This study began accrual in December 2020 and is open. Citation Format: Anusha Kalbasi, Fritz C. Eilber, Arun Singh, Bartosz Chmielowski, Nicholas Bernthal, Brooke Crawford, Joseph G. Crompton, Varand Ghazikhanian, Leanne Seeger, Kambiz Motamedi, Michael L. Douek, Carol Felix, Vincent Basehart, Helena Escuin-Ordinas, Marisol Quintero, Sonia Macia. A phase I study of intratumoral BO-112 and nivolumab for resectable soft tissue sarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT221.

Purpose Given the diverse and aggressive nature of soft tissue sarcomas (STSs), a need exists for more-precise therapy. Patient-derived orthotopic xenografts (PDOXs) provide a unique platform for personalized treatment. Thus, identification of patient and treatment factors that predict PDOX establishment is important. This study assessed the feasibility of incorporating PDOXs into the clinical setting and identifying factors associated with PDOX establishment. Patients and Methods From May 2015 to May 2016, 107 patients with biopsy-proven or potential STS were enrolled. Tumor samples were obtained intraoperatively and orthotopically implanted into nude mice in the corresponding anatomic location. PDOXs were considered established after engraftment and serial passage. Factors associated with establishment were analyzed by logistic regression and time to establishment by time-to-event analysis. Results Only high-grade tumors established (32 of 72 [44.4%]). The establishment rate (ER) varied by neoadjuvant therapy and treatment response, with the highest ER among untreated high-grade tumors (26 of 42 [61.9%]). Tumors exposed to radiation preoperatively did not establish (zero of 11 [0%]), and tumors exposed to neoadjuvant chemotherapy had a lower ER (31.9%) than untreated tumors. Only STSs with minimal pathologic response to neoadjuvant treatment (≤ 30%) established a PDOX (six of 18 [33.3%]). Median establishment time was 54 days, which varied by neoadjuvant therapy but was not statistically significant ( P = .180). Conclusion To our knowledge, in the largest STS PDOX study to date, we demonstrate a 62% ER among untreated high-grade tumors with a median establishment time of 54 days. Neoadjuvant therapy, particularly radiation, and pathologic response to treatment were associated with a reduced rate of PDOX establishment.

Background Inguinodynia, defined as pain lasting >3 months after inguinal hernia repair, remains the major complication of hernia operation. We sought to determine the effect of direct perineural infiltration on acute pain and inguinodynia after open inguinal hernia repair. Methods Patients who presented with an inguinal hernia at a university teaching hospital were evaluated prospectively and randomized to either (1) percutaneous ilioinguinal nerve block or (2) percutaneous ilioinguinal nerve block with additional perineural infiltration of the ilioinguinal, iliohypogastric, genitofemoral nerves. All patients in each group received a total of 12 mL of 0.5% bupivacaine. Self-reported faces of pain level (1–10), minutes to discharge from the recovery room, narcotic quantity consumed (oxycodone 5 mg/paracetamol 325 mg), days on narcotics, and incidence of inguinodynia at 3 months were all recorded. Results Ninety-two patients were randomized in the study. Patients who received perineural bupivacaine infiltration of nerves had less recovery room pain (1.3 vs 3.9, P P = .047) and consumed fewer narcotics (9.7 vs 15.1 doses, P = .010). The incidence of inguinodynia at 3 months was less in the treatment group (8.2% vs 27.9%, P = .013). Conclusion We have implemented a novel and inexpensive method of local nerve blockade that decreases pain immediately after operation and at 3 months postoperatively. Furthermore, our method leads to shorter recovery room stay and fewer narcotics after operation.

11546 Background: Surveillance imaging of patients with retroperitoneal liposarcoma (RP-LPS) following surgical resection is based on a projected risk of locoregional and distant recurrence. The duration of surveillance is not well defined as the long-term natural history of RP-LPS after treatment is poorly understood. We evaluate a cohort of RP-LPS patients—without evidence of disease 10 years following initial resection—to assess the long-term risk of recurrence and disease-specific survival (DSS). Methods: The prospectively maintained UCLA Sarcoma Database was used to identify RP-LPS patients who demonstrated 10-year progression-free survival (10yr-PFS) after initial diagnosis and treatment. Patients in the 10yr-PFS cohort were subsequently evaluated for recurrence and DSS. Time intervals start at date of initial surgical resection. Cox proportional hazards models were used to determine factors associated with recurrence and DSS. Results: From 1972-2010, 76 patients with RP-LPS had at least 10 years of follow-up. Of these, 37 (49%) demonstrated 10yr-PFS. Median follow-up was 15 years (range 10-35 years). Among the 10yr-PFS patients, 43% (16/37) developed a recurrence >10 years after the initial surgery, and 19% (7/37) died of disease. Neither long-term recurrence nor DSS were significantly associated with age, sex, tumor size, LPS subtype, surgical margin, or peri-operative treatment with radiation or chemotherapy (Table). Conclusions: Patients with primary RP-LPS treated with surgical resection +/- multimodality therapy have a long-term risk of recurrence and disease-specific death that is unacknowledged by current surveillance imaging guidelines. Among the patients with a 10yr-PFS, 43% developed a recurrence and 19% died of disease. These findings suggest a need for lifelong surveillance imaging in patients with RP-LPS.[Table: see text]

Although immunosuppression has been a key component to the success of solid-organ transplantation, the morbidity associated with long-term immunosuppression remains a substantial burden, particularly as recipients of transplants live longer. Indeed, malignancy is one of the most common reasons for mortality following transplantation and the most common of these cancers are cutaneous in origin. Recently, the incidence of these malignancies has been on the rise, partly due to the fact that recipients of these transplants are living longer as a result of improvements in surgical technique, immunosuppression and perioperative management. Although there have been initiatives to increase awareness of cutaneous malignancies following transplantation, such programs are not standardized and there continues to be gaps in skin cancer education and post-operative surveillance. This review provides an update on the epidemiology, risk factors, clinical management, prevention and surveillance of cutaneous malignancies.

The new edition of the American Joint Committee on Cancer staging system for melanoma builds on the foundation of prior editions but has several important improvements. The availability of regional nodal staging using sentinel lymph node biopsy (with subsequent follow-up) has resulted in more accurate prognostication for patients and clinicians. This facilitates identification of those at higher risk for recurrence, and allows for the appropriate selection of patients for new adjuvant therapy and clinical trials. Although more complex than previous editions, the eighth edition will provide granularity to outcome analysis based on more precise risk stratification.

Sarcomas of soft tissue and bone are mesenchymal malignancies that can arise in any anatomic location, most commonly the extremity, retroperitoneum, and trunk. Even for lower grade histologic subtypes, local recurrence can cause significant morbidity and even disease-related death. Although surgery remains the cornerstone of local control, perioperative radiation and systemic therapy are often important adjuvants. This review will summarize the current therapeutic approaches for local control of soft tissue and bone sarcomas.

Highlights • Nasopharyngeal mucosal melanoma is a rare pathology with an unclear etiology and oftentimes obscure clinical presentation. • We present a report of a lady who had a complete response to systemic treatment of metastatic melanoma of unknown origin. • Six years later, a diagnosis of primary nasopharyngeal melanoma was made after an extensive work-up for recurrent symptoms of severe right-sided epistaxis and hearing loss. • Surgical resection was performed followed by radiation therapy. The patient has since been without evidence of recurrent or metastatic disease and resolution of bleeding., Introduction Primary nasopharyngeal melanoma is an exceedingly rare pathology with unclear etiology and oftentimes obscure clinical presentation. Despite improved diagnostic capabilities, these lesions are often diagnosed at an advanced stage and associated prognosis is poor, partly due to high rates of recurrences and metastasis. Presentation of case A 74-year-old woman was diagnosed with metastatic melanoma to the liver, of unknown primary. Just prior to the time of diagnosis, she experienced several episodes of severe epistaxis which she managed conservatively. Her symptoms eventually subsided without further medical evaluation. The patient was initially treated with interleukin-2 (IL-2) for her advanced disease, but her cancer progressed. She was then enrolled in a protocol for percutaneous hepatic perfusion (PHP) with melphalan and had complete radiographic resolution of disease, yet her nosebleeds recurred and persisted despite conservative measures. Six years after her initial diagnosis, a nasopharyngoscopy demonstrated a pigmented lesion in the posterior nasopharynx. Surgical resection was performed (pathology consistent with mucosal melanoma) followed by radiation therapy. She has since had complete resolution of bleeding and shows no evidence of cancer. Discussion To our knowledge, this is the first report of a diagnosis of primary nasopharyngeal melanoma 6-years following complete remission of metastatic disease. Surgery remains the primary treatment for disease and symptom control in this setting. Conclusion Timely diagnosis of nasopharyngeal melanomas remains challenging. Thorough clinical evaluations should be performed in such patients, and attention should be paid to recurrent and persistent symptoms, such as epistaxis and hearing loss. This may allow for earlier detection of primary disease.

BACKGROUND: Here we describe the Systematically Tabulated Outcomes Research Matrix (STORM) method to generate research questions from pre-existing databases with the aim of improving patient outcomes. MATERIALS AND METHODS: STORM can be applied to a database by tabulating its variables into a matrix of independent variables (y-axis) and dependent variables (x-axis) and then applying each unique pairing of an independent and dependent variable to a patient population to generate potentially meaningful research questions. RESULTS: To demonstrate this methodology and establish proof-of-principle, STORM was applied on a small scale to the National Trauma Data Bank and generated at least seven clinically meaningful research questions. CONCLUSION: When coupled with rigorous clinical judgment, the STORM approach complements the traditional method of hypothesis formation and can be generalized to outcomes research using registry databases across different medical specialties. Language: en

// Elizabeth Shurell 1, * , Arun S. Singh 2, 7, * , Joseph G. Crompton 1 , Sarah Jensen 2 , Yunfeng Li 3 , Sarah Dry 3, 7 , Scott Nelson 3, 7 , Bartosz Chmielowski 2, 7 , Nicholas Bernthal 4, 7 , Noah Federman 2, 7 , Paul Tumeh 5, 7 , Fritz C. Eilber 1, 6, 7 1 Division of Surgical Oncology, Department of Surgery, University of California, Los Angeles, CA 90095, USA 2 Department of Hematology/Oncology, University of California, Los Angeles, CA 90095, USA 3 Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA 90095, USA 4 Department of Orthopaedic Surgery, University of California, Los Angeles, CA 90095, USA 5 Department of Dermatology, University of California, Los Angeles, CA 90095, USA 6 Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095, USA 7 UCLA JCCC Sarcoma Program, University of California, Los Angeles, CA 90095, USA * indicates co-first authors Correspondence to: Fritz C. Eilber, email: fceilber@mednet.ucla.edu Keywords: immune microenvironment, MPNST, PD-L1, CD8, sarcoma Received: June 29, 2016 Accepted: August 16, 2016 Published: August 31, 2016 ABSTRACT Background: Malignant peripheral nerve sheath tumor (MPNST) is an aggressive sarcoma with few treatment options. Tumor immune state has not been characterized in MPNST, and is important in determining response to immune checkpoint blockade. Our aim was to evaluate the expression of programmed death-ligand 1 (PD-L1), programmed cell death protein 1 (PD-1), and presence of CD8+ tumor infiltrating lymphocytes (TILs) in MPNST, and correlate these findings with clinical behavior and outcome. Results: PD-L1 staining of at least 1% was seen in 0/20 nerves, 2/68 benign lesions and 9/53 MPNST. Two of 68 benign lesions and 7/53 (13%) MPNST had at least 5% PD-L1 staining. CD8 staining of at least 5% was seen in 1/20 (5%) nerves, 45/68 (66%) benign lesions and 30/53 (57%) MPNST. PD-L1 was statistically more prevalent in MPNST than both nerves and benign lesions (p=0.049 and p=0.008, respectively). Expression of PD-1 was absent in all tissue specimens. There was no correlation of PD-L1 or CD8 expression with disease state (primary versus metastatic) or patient survival. Methods: A comprehensive PNST tissue microarray was created from 141 surgical specimens including primary, recurrent, and metastatic MPNST (n=53), neurofibromas (n=57), schwannoma (n=11), and normal nerve (n=20). Cores were stained in triplicate for PD-L1, PD-1, and CD8, and expression compared between tumor types. These data were then examined for survival correlates in 35 patients with primary MPNST. Conclusions: MPNST is characterized by low PD-L1 and absent PD-1 expression with significant CD8+ TIL presence. MPNST immune microenvironment does not correlate with patient outcome.

// Elizabeth Shurell 1, * , Maria E. Vergara-Lluri 2, * , Yunfeng Li 3 , Joseph G. Crompton 1 , Arun Singh 4 , Nicholas Bernthal 5 , Hong Wu 3 , Fritz C. Eilber 1 , Sarah M. Dry 2 1 Division of Surgical Oncology, University of California, Los Angeles, CA 90095, USA 2 Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA 90095, USA 3 Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095, USA 4 Department of Hematology/Oncology, University of California, Los Angeles, CA 90095, USA 5 Department of Orthopaedic Surgery, University of California, Los Angeles, CA 90095, USA * Co-first author Correspondence to: Fritz C. Eilber, email: fceilber@mednet.ucla.edu Keywords: NY-ESO-1, sarcoma, MPNST, liposarcoma, immunotherapy Received: July 28, 2016 Accepted: September 09, 2016 Published: September 17, 2016 ABSTRACT Background: Immunotherapy targeting cancer-testis antigen NY-ESO-1 shows promise for tumors with poor response to chemoradiation. Malignant peripheral nerve sheath tumors (MPNSTs) and liposarcomas (LPS) are chemoresistant and have few effective treatment options. Materials Methods: Using a comprehensive tissue microarray (TMA) of both benign and malignant tumors in primary, recurrent, and metastatic samples, we examined NY-ESO-1 expression in peripheral nerve sheath tumor (PNST) and adipocytic tumors. The PNST TMA included 42 MPNSTs (spontaneous n = 26, NF1-associated n = 16), 35 neurofibromas (spontaneous n = 22, NF-1 associated n = 13), 11 schwannomas, and 18 normal nerves. The LPS TMA included 48 well-differentiated/dedifferentiated (WD/DD) LPS, 13 myxoid/round cell LPS, 3 pleomorphic LPS, 8 lipomas, 1 myelolipoma, and 3 normal adipocytic tissue samples. Stained in triplicate, NY-ESO-1 intensity and density were scored. Results: NY-ESO-1 expression was exclusive to malignant tumors. 100% of myxoid/round cell LPS demonstrated NY-ESO-1 expression, while only 6% of WD/DD LPS showed protein expression, one of which was WD LPS. Of MPNST, 4/26 (15%) spontaneous and 2/16 (12%) NF1-associated MPNSTs demonstrated NY-ESO-1 expression. Strong NY-ESO-1 expression was observed in myxoid/round cell and dedifferentiated LPS, and MPNST in primary, neoadjuvant, and metastatic settings. Conclusions: We found higher prevalence of NY-ESO-1 expression in MPNSTs than previously reported, highlighting a subset of MPNST patients who may benefit from immunotherapy. This study expands our understanding of NY-ESO-1 in WD/DD LPS and is the first demonstration of staining in a WD LPS and metastatic/recurrent myxoid/round cell LPS. These results suggest immunotherapy targeting NY-ESO-1 may benefit patients with aggressive tumors resistant to conventional therapy.

BACKGROUND/PURPOSE: The mechanism of injury (MOI) may serve as a useful adjunct to injury scoring systems in pediatric trauma outcomes research. The objective is to determine the independent effect of MOI on case fatality and functional outcomes in pediatric trauma patients. METHODS: Retrospective review of pediatric patients ages 2 to 18 years in the National Trauma Data Bank from 2002 through 2006 was done. Mechanism of injury was classified by the International Classification of Diseases, Ninth Revision, E codes. The main outcome measures were mortality, discharge disposition (home vs rehabilitation setting), and functional impairment at hospital discharge. Multiple logistic regression was used to adjust for injury severity (using the Injury Severity Score and the presence of shock upon admission in the emergency department), age, sex, and severe head or extremity injury. RESULTS: Thirty-five thousand ninety-seven pediatric patients in the National Trauma Data Bank met inclusion criteria. Each MOI had differences in the adjusted odds of death or functional disabilities as compared with the reference group (fall). The MOI with the greatest risk of death was gunshot wounds (odds ratio [OR], 3.52; 95% confidence interval [CI], 2.23-5.54 95). Pediatric pedestrians struck by a motor vehicle have the highest risk of locomotion (OR, 3.30; 95% CI, 2.89-3.77) and expression (OR, 1.65; 95% CI, 1.22-2.23) disabilities. CONCLUSION: Mechanism of injury is a significant predictor of clinical and functional outcomes at discharge for equivalently injured patients. These findings have implications for injury prevention, staging, and prognosis of traumatic injury and posttreatment planning. Language: en

Basic science research suggests that sex hormones affect survival after traumatic shock. This study sought to determine the independent effect of gender on mortality among trauma patients in different hormone-related age groups.Review of severely injured trauma patients with shock included in the National Trauma Databank. Patients were stratified into three groups on the basis of likely hormonal status: prehormonal (age, 0-12 years), hormonal (age,13-64 years), and posthormonal (age, ≥ 65 years). Multiple logistic regression was used to analyze the independent effect of gender on mortality in each group, adjusting for anatomic and physiologic injury severity.A total of 48,394 patients met our inclusion criteria (Injury Severity Score ≥ 16 and systolic blood pressure90 mm Hg). Crude mortality was higher (p0.05) for males in all categories: prehormonal = 29% for males (n = 3,553) versus 24% for females (n = 1,831); hormonal = 34% for males (n = 26,778) versus 30% for females (n = 8,677) and posthormonal = 36% for males (n = 4,280) versus 31% for females (n = 3,275). After adjusting for covariates, women in the hormonally active group had a 14% decreased odds of death (0.86 [95% CI, 0.76-0.93]) compared with men. Females did not exhibit this survival advantage in the prehormonal (odds of death = 0.92 [0.74-1.14]) or posthormonal (odds of death = 0.90 [0.76-1.05]) groups.Females aged between 13 and 64 years exhibit significantly lower mortality than males after trauma-associated shock. This outcome difference is lost at the extremes of age (preadolescent children and individuals aged ≥ 65 years) where the effects of sex hormones are absent or diminished. These findings suggest that hormonal differences play a role in the gender-based outcome disparities after traumatic shock.

Background The Revised Trauma Score (RTS) is commonly used to assess physiologic injury; however its use is limited by missing data. This study compares different parameters of physiologic injury assessment in their ability to predict mortality after trauma. Methods Adult patients in the National Trauma Data Bank (NTDB version 7.0) were analyzed, and the following physiologic injury parameters were compared: RTS, systolic blood pressure (SBP), shock (SBP ≤ 90 mm Hg), Glasgow coma scale-total (GCS-T), and GCS-motor (GCS-M). Areas under the receiver-operating characteristic curves (AUROC) were calculated for unadjusted and multivariate regression models to predict mortality after trauma. Results There were 1,484,648 patients who met inclusion criteria. In unadjusted analyses, RTS had the highest proportion of missing data (21%) and was highly predictive of mortality (AUROC = 0.85). SBP and shock had a much lower AUROC of 0.67 and 0.66, respectively, but had many fewer missing cases. The combination parameters of GCS-M with SBP or GCS-M with shock showed AUROC comparable to RTS (0.85) with approximately 80,000 fewer missing cases. Conclusion The discriminatory power of RTS is significantly better than SBP, shock, or GCS alone. Given the limitation of missing data associated with RTS, the combination of SBP and GCS-M is a more reliable and equally effective method of assessing physiologic injury severity in studying trauma outcomes.

In the original article the middle initial of Nicholas D. Klemen was inadvertently omitted. On the first page of the original article, under the heading A Novel Way to Fight Cancer, there was an error in the third sentence. The corrected text is as follows: For example, the presence of T cells within tumors of colorectal origin can be a superior predictor of patient survival compared with the standard histopathologic methods currently used to stage colorectal cancer.6,7.

Background Studies of sexual dimorphism in trauma outcomes suggest that women have a survival advantage compared to equivalently injured men. It is unknown if this gender disparity is mediated by potentially life-threatening complications. Objective To determine (1) if there is a sex-based differences in the odds of developing inpatient complications after trauma, and (2) if are these complications associated with death among trauma patients. Methods Review of adult trauma patients admitted to hospitals in the National Trauma Data Bank that report complications. Patient and injury severity covariates were adjusted using multiple logistic regression and the independent effect of sex on developing complications and associated mortality was determined. Results A total of 681,730 adult patients met the inclusion criteria of hospital admission ≥3 days. Women demonstrated a 21% lower adjusted risk of death compared to males (OR 0.79, 95% CI 0.76–0.83). Females had decreased adjusted odds of developing life-threatening complications including pneumonia, acute respiratory distress syndrome, acute renal failure and pulmonary embolism. However, when compared to males with life-threatening complications, females with complications were found to be at greater risk of dying. Conclusion This study demonstrates that women are less likely than men to develop inpatient complications, suggesting that the survival advantage among women after traumatic injury may involve a reduced susceptibility to developing life-threatening complications.

There has been a repeal of the universal helmet law in several states despite definitive evidence that helmets reduce mortality, traumatic brain injury, and hospital expenditures. Opponents of the universal helmet law have successfully claimed that helmets should not be required because of greater torque on the neck, which is thought to increase the likelihood of a cervical spine injury. There is currently insufficient evidence to counter claims that helmets do not increase the risk of cervical spine injury after a motorcycle collision. The objective of this study was to determine the impact of motorcycle helmets on the likelihood of developing a cervical spine injury after a motorcycle collision.We reviewed cases in the National Trauma Databank (NTDB) v7.0 involving motorcycle collisions. Multiple logistic regression was used to analyze the independent effect of helmets on cervical spine injury. Cases were adjusted for age, race, sex, insurance status, anatomic (Injury Severity Score) and physiologic injury severity (systolic blood pressure90 mmHg), and head injury (Abbreviated Injury Score3).Between 2002 and 2006, 62,840 cases of motorcycle collision were entered into the NTDB; 40,588 had complete data and were included in the adjusted analysis. Helmeted riders had a lower adjusted odds (0.80 [CI 0.72 to 0.90]) and a lower proportion of cervical spine injury (3.5% vs 4.4%, p0.05) compared with nonhelmeted riders.Helmeted motorcyclists are less likely to suffer a cervical spine injury after a motorcycle collision. This finding challenges a long-standing objection to mandatory helmet use that claims helmets are associated with cervical spine injury. Re-enactment of the universal helmet law should be considered in states where it has been repealed.

Surgery is rapidly becoming a part of public health initiatives in developing countries. In collaboration with the Sierra Leone Ministry of Health and Sanitation, a team of local surgeons and surgeons from the organization Surgeons OverSeas (SOS) used the WHO Tool for Situational Analysis to Assess Emergency Surgical Care to quantify surgical capacity in Sierra Leone. These data were then compared to data collected from the Medical and Surgical History of the Civil War, a work documenting surgical care and hospitals during the US Civil War. There are 0.2 government hospital surgeons/100,000 people in Sierra Leone compared to 300 surgeons/100,000 soldiers in the Union Army. In Sierra Leone it is rare to have running water, fuel, anesthesia, and reliable X-rays. In comparison, US Civil War hospitals had reliable running water, fuel, and anesthesia. It is rare to manage open fractures, limb dislocations, amputations, and conditions requiring chest tubes in Sierra Leone, while these procedures were commonly employed in US Civil War hospitals. Government hospitals in present day Sierra Leone lack the infrastructure, personnel, supplies, and equipment to adequately provide emergency and essential surgical care. In a comparison of present day Sierra Leonean and US Civil War hospitals, the US Civil War facilities are equivalent and in many ways superior. It is hoped that such a comparison will aid advocacy efforts so that greater resources are devoted to improving emergency and essential surgical care in low- and middle-income countries.

Background Missing data has remained a major disparity in trauma outcomes research due to missing race and insurance data. Multiple imputation (M.IMP) has been recommended as a solution to deal with this major drawback. Study Design Using the National Data Trauma Bank (NTDB) as an example, a complete dataset was developed by deleting cases with missing data across variables of interest. An incomplete dataset was then created from the complete set using random deletion to simulate the original NTDB, followed by five M.IMP rounds to generate a final imputed dataset. Identical multivariate analyses were performed to investigate the effect of race and insurance on mortality in both datasets. Results Missing data proportions for known trauma mortality covariates were as follows: age-4%, gender-0.4%, race-8%, insurance-17%, injury severity score-6%, revised trauma score-20%, and trauma type-3%. The M.IMP dataset results were qualitatively similar to the original dataset. Conclusion M.IMP is a feasible tool in NTDB for handling missing race and insurance data.

Background Studies have shown racial disparities in outcomes after motor vehicle crashes; however, it is currently unknown if race impacts the likelihood of mortality after a motorcycle crash (MCC). The primary objective of this study was to determine if race is associated with MCC mortality. Methods We performed a retrospective cross-sectional analysis of MCCs included in the National Trauma Data Bank between 2002 and 2006. Multiple logistic regression was used to adjust for age, sex, insurance status, year, helmet use, and injury severity characteristics. Results Black patients had a 1.58 (95% confidence interval, 1.28–1.97) increased odds of mortality after a MCC, but were more likely to use a helmet (1.30; 95% confidence interval, 1.19–1.43) compared with their white counterparts (n = 62,840). Conclusions Black motorcyclists appear more likely to die after a MCC compared with whites. Although the reasons for this disparity are unclear, these data suggest that resources beyond encouraging helmet use are necessary to reduce fatalities among black motorcyclists.

Background The incidence of motorcycle fatalities over the last 10 y has nearly doubled. There is considerable evidence that motorcycle helmets save lives, but there are little data regarding the impact that helmets have on functional outcomes after a motorcycle crash. The objective of this study was to determine the difference between helmeted and non-helmeted motorcyclists in the odds of developing a functional deficit at discharge in three domains: speech, locomotion, and feeding. Methods Reviewed cases in the National Trauma Databank v7.0 involved in motorcycle collisions. Multiple logistic regression was used to analyze the effect of helmets on mortality and functional outcomes, adjusting for age, race, gender, insurance status, anatomic and physiologic injury severity, and head injury. Results The adjusted odds of mortality (0.75; 95% CI 0.65–0.86) and functional deficits in speech (0.82; 95% CI 0.69–0.97), locomotion (1.19; 95% CI 1.11–1.29), and feeding (0.96 95% CI 0.84–1.08) among helmeted riders was compared with non-helmeted motorcyclists with equivalent injuries. Conclusion Helmeted motorcyclists are less likely to die and develop a deficit in speech after a motorcycle collision. These data support that motorcycle helmets are important in preventing functional deficits related to head injury.

Traumatic ventricular septal defect (VSD) is a widely-recognized complication of both penetrating and blunt trauma. Most cases are repaired operatively without the long-term complications of pulmonary hypertension and heart failure that are associated with unrepaired congenital VSD in the pediatric population. To our knowledge, this is the first case report of a patient with a traumatic VSD who declined surgical repair at the time of injury and subsequently developed long-term complications of pulmonary hypertension and heart failure. With nearly 20 years of follow-up, this case demonstrates that the absence of surgical treatment in asymptomatic adult patients at the time of injury can lead to long-term complications associated with VSD. This case also shows that aggressive surgical treatment in patients with severe pulmonary vascular disease and heart failure secondary to traumatic VSD can be performed safely and should be considered in cases refractory to efficacious medical interventions.

Motorcycle collisions are increasing at a precipitous rate, and reliable and valid data regarding all aspects of helmet safety are needed to better inform ongoing debates on mandatory helmet laws. The objective of this study was to determine the effect of motorcycle helmets on the likelihood of a facial injury after motorcycle collisions, using data from the National Trauma Data Bank, version 7.0, on 46 362 patients from January 1, 2002, through December 31, 2006. Multiple logistic regression was used to analyze the independent association between helmets and facial injury with adjustment for potential confounders. Helmeted motorcyclists were less likely to suffer facial injuries after a motorcycle collision, with a lower adjusted odds ratio of facial injury (0.40; 95% CI, 0.37-0.43) and a lower prevalence of specific types of facial injury compared with their nonhelmeted counterparts.

Background Recent debate concerns the most appropriate definition of hypotension. Some have advocated raising the systolic blood pressure (BP) threshold to 110 mm Hg while others favor 80 mm Hg. Hypothesis The optimal definition of hypotension differs by age group. Design An analysis was performed of trauma victims 18 years and older in the National Trauma Data Bank, excluding burn injury patients and those with incomplete data. Setting Injured patients who were hospitalized in various trauma centers across the continental United States. Patients Three age groups were identified for analysis as follows: 18 to 35 years, 36 to 64 years, and 65 years and older. One hundred one multiple logistic regression analyses were performed for each population. Hypotension was sequentially defined as an emergency department systolic BP (SBP) of 50 to 150 mm Hg to see which model best predicted mortality, adjusting for demographic and injury covariates. The discriminatory power of each model was measured using the area under the receiver operating characteristic (AUROC) curve. Optimally defined hypotension was identified as the model with the highest AUROC curve. Main Outcomes Measure In-hospital mortality. Results A total of 902 852 patients (median age, 44 years; 66.2% men) were analyzed. Overall mortality was 4.1%. Optimal emergency department SBP cutoff values for hypotension were 85 mm Hg for patients aged 18 to 35 years, 96 mm Hg for patients aged 36 to 64 years, and 117 mm Hg for elderly patients. Conclusions For patients younger than 65 years, the classic definition of hypotension as an emergency department SBP less than 90 mm Hg remains optimal. With increasing involvement of elderly individuals in trauma and their peculiarity as a comorbid state, there is a need to redefine what is presently defined as a cutoff value for hypotension in elderly patients.