Explainable Model Using Shapley Additive Explanations Approach on Wound Infection after Wide Soft Tissue Sarcoma Resection: "Big Data" Analysis Based on Health Insurance Review and Assessment Service Hub.

Background and Objectives: Soft tissue sarcomas represent a heterogeneous group of malignant mesenchymal tissues. Despite their low prevalence, soft tissue sarcomas present clinical challenges for orthopedic surgeons owing to their aggressive nature, and perioperative wound infections. However, the low prevalence of soft tissue sarcomas has hindered the availability of large-scale studies. This study aimed to analyze wound infections after wide resection in patients with soft tissue sarcomas by employing big data analytics from the Hub of the Health Insurance Review and Assessment Service (HIRA). Materials and Methods: Patients who underwent wide excision of soft tissue sarcomas between 2010 and 2021 were included. Data were collected from the HIRA database of approximately 50 million individuals' information in the Republic of Korea. The data collected included demographic information, diagnoses, prescribed medications, and surgical procedures. Random forest has been used to analyze the major associated determinants. A total of 10,906 observations with complete data were divided into training and validation sets in an 80:20 ratio (8773 vs. 2193 cases). Random forest permutation importance was employed to identify the major predictors of infection and Shapley Additive Explanations (SHAP) values were derived to analyze the directions of associations with predictors. Results: A total of 10,969 patients who underwent wide excision of soft tissue sarcomas were included. Among the study population, 886 (8.08%) patients had post-operative infections requiring surgery. The overall transfusion rate for wide excision was 20.67% (2267 patients). Risk factors among the comorbidities of each patient with wound infection were analyzed and dependence plots of individual features were visualized. The transfusion dependence plot reveals a distinctive pattern, with SHAP values displaying a negative trend for individuals without blood transfusions and a positive trend for those who received blood transfusions, emphasizing the substantial impact of blood transfusions on the likelihood of wound infection. Conclusions: Using the machine learning random forest model and the SHAP values, the perioperative transfusion, male sex, old age, and low SES were important features of wound infection in soft-tissue sarcoma patients.

High Community-Level Social Vulnerability is Associated with Worse Recurrence-Free Survival (RFS) After Resection of Extremity and Truncal Soft Tissue Sarcoma.

BACKGROUND: Although social vulnerability has been associated with worse postoperative and oncologic outcomes in other cancer types, these effects have not been characterized in patients with soft tissue sarcoma. This study evaluated the association of social vulnerability and oncologic outcomes. METHODS: The authors conducted a single-institution cohort study of adult patients with primary and locally recurrent extremity or truncal soft tissue sarcoma undergoing resection between January 2016 and December 2021. The social vulnerability index (SVI) was measured on a low (SVI 1-39%, least vulnerable) to high (60-100%, most vulnerable) SVI scale. The association of SVI with overall survival (OS) and recurrence-free survival (RFS) was evaluated by Kaplan-Meier analysis and Cox proportional hazard regression. RESULTS: The study identified 577 patients. The median SVI was 44 (interquartile range [IQR], 19-67), with 195 patients categorized as high SVI and 265 patients as low SVI. The median age, tumor size, histologic subtype, grade, comorbidities, stage, follow-up time, and perioperative chemotherapy and radiation utilization were similar between the high and low SVI cohorts. The patients with high SVI had worse OS (p = 0.07) and RFS (p = 0.016) than the patients with low SVI. High SVI was independently associated with shorter RFS in the multivariate analysis (hazard ratio, 1.64; 95% confidence interval, 1.06-2.54) but not with OS (HR, 1.47; 95% CI 0.84-2.56). CONCLUSION: High community-level social vulnerability appears to be independently associated with worse RFS for patients undergoing resection of extremity and truncal soft tissue sarcoma. The effect of patient and community-level social risk factors should be considered in the treatment of patients with extremity sarcoma.

What is the diagnostic accuracy of fluorescence-guided surgery for margin assessment in appendicular bone and soft tissue tumors? - A systematic review of clinical studies.

BACKGROUND: Fluorescence-guided surgery (FGS) is a novel technique to successfully assess surgical margins intraoperatively. Investigation and adoption of this technique in orthopaedic oncology remains limited. METHODS: The PRISMA guidelines were followed for this manuscript. Our study was registered on PROSPERO (380520). Studies describing the use of FGS for resection of bone and soft tissue sarcomas (STS) on humans were included. Diagnostic performance metrics (sensitivity, specificity, positive predictive value [PPV], negative predictive value [NPV] and accuracy) and margin positivity rate were the outcomes assessed. RESULTS: Critical appraisal using the Joanna Brigs Institute checklists showed significant concerns for study quality. Sensitivity of FGS ranged from 22.2 % to 100 % in three of the four studies assessing his metrics; one study in appendicular tumors in the pediatric population reported 0 % sensitivity in the three cases included. Specificity ranged from 9.38 % to 100 %. PPV ranged from 14.6 % to 70 % while NPV was between 53.3 % and 100 %. The diagnostic accuracy ranged from 21.62 % to 92.31 %. Margin positivity rate ranged from 2 % to 50 %, with six of the seven studies reporting values between 20 % and 50 %. CONCLUSIONS: FSG is a feasible technique to assess tumor margins in bone and STS. Reported performance metrics and margin positivity rates vary widely between studies due to low study quality and high heterogeneity in dying protocols. LEVEL OF EVIDENCE: Level III, diagnostic study.

Preoperative radiation therapy increases adherence in patients with high-risk extremity soft tissue sarcoma.

BACKGROUND: Surgery and radiation therapy remain the standard of care for patients with high-grade extremity soft tissue sarcoma that are >5 cm. Radiation therapy is time and labor-intensive for patients, and social determinants of health may affect adherence. The aim of this study was to define demographic, clinical, and treatment factors associated with the completion of radiation therapy and determine if preoperative radiation therapy improved adherence compared to postoperative radiation therapy. METHODS: The cohort included patients in the National Cancer Database with high-grade extremity soft tissue sarcoma >5 cm without nodal or distant metastases who received limb-sparing surgery and radiation therapy with microscopically negative R0 margins. Multivariable logistic regression analyses identified factors associated with radiation therapy sequencing and adherence (defined as completion of 50 Gy preoperative radiation therapy or at least 60 Gy postoperative radiation therapy). A multivariable Cox Proportional Hazards model assessed overall survival. RESULTS: Among 2,145 patients, 47.1% received preoperative radiation therapy (n = 1,010), and 52.9% (n = 1135) received postoperative radiation therapy. A greater proportion of patients treated with preoperative (77.2%) versus postoperative radiation therapy (64.9%, P < .0001) received the recommended dose. More patients with private insurance (49.8% vs 35.3% Medicaid vs 44.9% Medicare, P = .011) and patients treated at an academic medical center (52.6% vs 47.4%, P < .001) received preoperative radiation therapy. Patients who received preoperative radiation therapy had lower odds of receiving insufficient doses of radiation therapy (odds ratio 0.34 [95% CI 0.27-0.47]). Neither radiation therapy adherence nor sequencing were independent predictors of overall survival. CONCLUSIONS: Patients who received preoperative radiation therapy were more likely to complete therapy and receive an optimal dose than patients treated with postoperative radiation therapy. Preoperative radiation therapy improves adherence and should be widely considered in patients with high-grade extremity soft tissue sarcoma, particularly in patients at risk for not completing therapy.

Radiological and histopathological assessment of bone infiltration in soft tissue sarcomas.

BACKGROUND: Deep soft tissue sarcomas are frequently in contact with bone. The therapeutic decision of a composite resection strategy may be challenging, which is usually based on clinical and radiological criteria. The aims of the study were to evaluate the overall frequency of bone and periosteal infiltration in these patients in whom composite resection was indicated, and evaluate the role of magnetic resonance imaging and bone scintigraphy in this scenario. METHODS: Forty-nine patients with a composite surgical resection (soft tissue sarcoma and bone), treated at a single institution between 2006 and 2018, were retrospectively included. Presurgical planning of the resection limits was based on clinical and imaging findings (magnetic resonance imaging and bone scintigraphy). Magnetic resonance imaging was performed in all patients (100%) and bone scintigraphy in 41 (83.7% of the cases). According to magnetic resonance imaging results, patients were divided into two groups: Group A, in which the tumor is adjacent to the bone without evidence of infiltration (n = 24, 48,9%), and Group B, patients with evidence of bone involvement by magnetic resonance imaging (n = 25, 51,1%). BS showed a pathological deposit in 28 patients (68.3%). Histological analysis of the resection specimen was preceded to identify bone and periosteal infiltration. For the analysis of the diagnostic validity of imaging tests, histological diagnosis was considered as the gold standard in the evaluation of STS bone infiltration. RESULTS: Histological bone infiltration was identified in 49% of patients and isolated periosteal infiltration in 14.3%. In terms of diagnostic accuracy, magnetic resonance imaging and bone scintigraphy sensitivity values were 92% and 90%, and their specificity values were 91.7% and 52.4%, respectively. CONCLUSIONS: The incidence of bone and periosteal infiltration of soft tissue sarcomas in contact with bone is high. Presurgical bone assessment by MRI has proven to be a sensitive and specific tool in the diagnosis of bone infiltration. Due to its high negative predictive value, BS is a useful test to rule out it. In those cases, in which there is suspicion of bone infiltration not confirmed by MRI, new diagnostic protocols should be established in order to avoid inappropriate resections.

Diagnostic accuracy of optical coherence tomography for surgical margin assessment of feline injection-site sarcoma.

The invasive, locally aggressive nature of feline injection-site sarcomas (FISSs) poses a unique challenge for surgeons to obtain complete margins with surgical excision. Optical coherence tomography (OCT), an imaging technology that uses light waves to generate real-time views of tissue architecture, provides an emerging solution to this dilemma by allowing fast, high-resolution scanning of surgical margins. The purpose of this study was to use OCT to assess surgical margins of FISS and to evaluate the diagnostic accuracy of OCT for detecting residual cancer using six evaluators of varying experience. Five FISSs were imaged with OCT to create a training set of OCT images that were compared with histopathology. Next, 25 FISSs were imaged with OCT prior to histopathology. Six evaluators of varying experience participated in a training session on OCT imaging after which each of the evaluators was given a dataset that included OCT images and videos to score on a scale from cancerous to non-cancerous. Diagnostic accuracy statistics were calculated. The overall sensitivity and specificity for classification of OCT images by evaluators were 78.9% and 77.6%, respectively. Correct classification rate of OCT images was associated with experience, while individual sensitivities and specificities had more variation between experience groups. This study demonstrates the ability of evaluators to correctly classify OCT images with overall low levels of experience and training and also illustrates areas where increased training can improve accuracy of evaluators in interpretation of OCT surgical margin images.

Unplanned excision of soft tissue sarcoma: does it impact the accuracy of intra-operative pathologic assessment at time of re-excision?

PURPOSE: An "unplanned excision" refers to soft tissue sarcomas excised without planning imaging studies and a diagnostic biopsy, resulting in the presence of residual disease and usually necessitating a re-excision procedure. We aimed to assess the impact of previous unplanned excisions on the intra-operative pathologic assessment at the time of re-excision, in terms of need to perform repeat assessments and the accuracy to predict margin status of the final pathologic specimen. METHODS: Data was collected for all patients with extremity soft tissue sarcoma who had undergone wide local excision limb salvage surgery or amputation between 2012 and 2017. Intra-operative pathologic assessment with frozen sections was performed in all cases and was classified as negative, negative but close (< 1 mm), and positive. RESULTS: A total of 173 patients with extremity soft tissue sarcoma were included, 54 in the unplanned excision group and 119 in the planned excision group. The accuracy of intra-operative pathologic assessment to predict the margin status on final pathology was similar between groups (87% unplanned vs. 90.7% planned excisions). However, the need for repeat intra-operative pathologic assessment and subsequent resection due to microscopically positive margins was found to be higher within the unplanned excision group ((p = 0.04), OR = 3.2 (95% CI: 1.1-9.1, p = 0.048)). CONCLUSIONS: Intra-operative pathologic assessment of resection margins had a similar accuracy in planned and unplanned excisions; however, unplanned excisions showed a higher risk of re-resection during the same surgical setting.

Cost Variance in Patients With Soft Tissue Sarcoma Who Develop Postoperative Wound Complications.

BACKGROUND: Wound complications after a soft-tissue sarcoma surgery are common, occurring in up to 30% to 40% of patients who undergo preoperative radiation therapy. Although risk factors for developing complications are well-known, there is a paucity of literature on the increased healthcare costs after a wound complication. The purpose of this study was to detail these additional costs after a soft-tissue sarcoma surgery. METHODS: A retrospective review of 99 patients from January 2013 to October 2019 was performed. Hospital and professional charges for the primary surgical procedure and any subsequent hospitalization or procedure related to a wound complication were compiled. Costs were inflated to 2019 dollars. RESULTS: Total costs were 21.3% higher for patients who developed a wound complication (P = 0.006). Most patients (32 of 42; 76.2%) who developed a complication required a return trip to the operating room. The average number of return trips was 1.2 (range 0 to 5). For each return trip to the operating room because of a wound complication, an associated increased overall cost of 13.2% was noted (P < 0.001). CONCLUSION: Wound complications after a soft-tissue sarcoma resection are common and add considerable expense to the episode of care. A reduction in wound complications may markedly decrease the cost of treating soft-tissue sarcomas and continues to be an opportunity for improvement.

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.

Perspectives on how to navigate cancer surgery in the breast, head and neck, skin, and soft tissue tumor in limited-resource countries during COVID-19 pandemic.

The rapidly spreading coronavirus infection (COVID-19) worldwide has contracted all aspects of health systems. Developing countries that mostly have a weaker healthcare system and insufficient resources are likely to be the most hardly affected by the pandemic. Cancers are frequently diagnosed in late stages with higher case-fatality rates compared to those in high-income countries. Delayed diagnosis, lack of cancer awareness, low adherence to treatment, and unequal or limited access to treatment are among the challenging factors of cancer management in developing countries. Elective cancer surgeries are often considered to be postponed during COVID-19 pandemic to preserve valuable hospital resources such as personal protection equipment, hospital bed, intensive care unit capacity, and manpower to screen and treat the affected individuals. However, specific considerations to defer cancer surgery in developing countries might need to be carefully adjusted to counterbalance between preventing COVID-19 transmission and preserving patients 'long-term life expectancy and quality of life.

The clinical outcomes of undifferentiated pleomorphic sarcoma (UPS): A single-centre experience of two decades with the assessment of PD-L1 expressions.

INTRODUCTION: Little is known about undifferentiated pleomorphic sarcoma (UPS) because of the low incidence and heterogeneous diagnosis of sarcoma. We investigated the oncologic outcomes of patients with UPS in a real-practice setting in association with adjuvant treatments and assessment of PD-L1 expression. MATERIALS AND METHODS: We retrospectively reviewed consecutive patients who were diagnosed with UPS in Asan Medical Center between January 1995 and December 2016. PD-L1 staining was performed using formalin-fixed paraffin-embedded tumour tissue by immunohistochemistry, and positive PD-L1 expression was defined as staining in ≥1% of tumour cells. The PD-L1 H-score, which was calculated for statistical analysis as intensity (0-3) multiplied by proportion (0-100), ranged from 0 to 300. RESULTS: Of 205 patients included in our analysis, 176 underwent a curative-intent operation for localised disease. The five-year disease-free survival (DFS) rate of resected UPS patients was 54.3%. Administration of adjuvant therapy did not overcome the poor prognostic factors such as primary tumour size (>5 cm) and locations, especially the abdomen and pelvis. The PD-L1 analysis was available for 114 patients, and 83 (72.8%) showed immunoreactivity for PD-L1 with weak (44/83), intermediate (29/83), and strong (10/83) staining intensities. The positive PD-L1 expression seemed to be associated with prolonged DFS, though no statistical significance was observed. CONCLUSION: Complete surgical resection was the most important UPS treatment strategy, and adjuvant radio- or chemotherapy was insufficient to improve survival. Our results raise the possibility that immunotherapy could be a breakthrough in the treatment of UPS patients.

Oncological outcome, functional results and costs after unplanned excision of musculoskeletal soft tissue sarcoma.

BACKGROUND: Treatment of soft tissue sarcomas (STS) should only be initiated once the diagnosis is fully established. Resection of tumors of unknown nature should be avoided. Nevertheless, specialized centers continue to face numbers of unplanned excisions (UPE) in STS. AIM: To compare oncologic and functional outcomes, number of surgeries, length of hospital stay and treatment costs of UPE versus planned excision (PE) in STS. METHOD: A retrospective single tertiary center study was performed on 201 patients. Survival, local and distant recurrence rates were compared between PE (n = 137) and UPE (n = 64). In a subgroup analysis of 60 patients, functional outcome (MSTS and TESS scores), and socio-economic impact (number of surgeries, length of hospital stay and treatment costs) in "functional planned excision" (fPE) group (n = 30) and "functional unplanned excision" (fUPE) group (n = 29) were compared. RESULTS: There was no significant difference in oncological outcome between PE and UPE. In the subgroup analysis, we found a non-significant difference in functional outcome. Patients in the fUPE had significantly more surgeries (3.5 vs. 1.4; p < 0.00001) and costs of their management was 64% higher than fPE (p = 0.048). Hospital stay was longer after fUPE but not statistically significant (18.3 days vs. 11.8 days; p = 0.13). CONCLUSION: Even though oncological and functional outcomes are comparable after PE and UPE of STS, the number of surgeries, length of hospital stay and treatment costs were higher in patients with UPE. Our data underscore the importance of specialized STS treatment centers including multidisciplinary management.

Diagnostic performance of MRI and histology in assessment of deep lipomatous tumours.

BACKGROUND: Deep lipomatous tumours can be benign lipomas or intermediate/locally recurring atypical lipomatous tumours (ALTs). Differentiating between these two entities clinically and radiologically is difficult. The aims of this study were to report a series of deep lipomatous tumours, comparing the clinical, radiological and pathological features of ALTs and lipomas; and to predict the likelihood of a lipomatous tumour being ALT based on anatomical site and MRI characteristics. METHODS: This was a retrospective review of patients with deep lipomatous tumours presenting over 6 years to a tertiary sarcoma centre, with preoperative MRI, and preoperative or postoperative histology including MDM2 gene analysis. Sensitivity, specificity, predictive values and accuracy in diagnosing ALT were calculated for MRI and histopathological features. RESULTS: Some 248 patients were included; 81 (32·7 per cent) had a final diagnosis of ALT. ALTs were larger than lipomas (median 19 versus 10 cm; P < 0·001); there was no ALT smaller than 5 cm. A tumour presenting in the lower limb was more likely to be an ALT than a lesion at any other site (48·4 versus 13·5 per cent; P < 0·001). In patients with lipomatous tumours at sites other than the lower limbs, MRI had a negative predictive value of 95 per cent for excluding ALT. CONCLUSION: Despite concern, most deep lipomatous tumours (nearly 70 per cent) are benign lipomas. Certain features imply that tumours are almost never ALT: smaller than 5 cm or located outside the lower limb with no suspicious characteristics on MRI. Tumours with these features might safely and confidently be managed outside tertiary sarcoma centres.

ANTECEDENTES: Los tumores lipomatosos profundos pueden ser lipomas benignos o tumores lipomatosos atípicos (atypical lipomatous tumour, ALT) con potencial de recidiva local/intermedia. Diferenciar estas dos entidades desde el punto de vista clínico es difícil. Los objetivos de este estudio fueron presentar una gran serie de tumores lipomatosos profundos, comparando las características clínicas, radiológicas y patológicas de los ALT y de los lipomas y predecir la probabilidad de que un tumor lipomatoso sea ALT según su localización anatómica y las características de la RNM. MÉTODOS: Revisión retrospectiva de pacientes con tumores lipomatosos profundos tratados en un centro terciario de sarcoma durante un período de 6 años, en los que se dispusiese de RNM preoperatoria y análisis MDM2 en el preoperatorio o postoperatorio. Se calculó la sensibilidad, la especificidad, el valor predictivo y la precisión diagnóstica de la RNM y de las características histopatológicas para el diagnóstico de ALT. RESULTADOS: Se incluyeron 248 pacientes, de los que en solo 81 (32,7%) se estableció un diagnóstico final de ALT. Los ALT fueron más grandes que los lipomas (19 versus 10 cm, P < 0,001) y no hubo ningún ALT de tamaño menor de 5 cm. Hubo una mayor probabilidad de que un tumor fuera ALT si se presentaba en las extremidades inferiores en comparación con cualquier otra localización (48,4% versus 13,5%, P < 0,001). En pacientes con tumores lipomatosos localizados en otros lugares que no fueran las extremidades inferiores, la RMN tuvo un valor predictivo negativo del 95,5% para excluir la ALT. CONCLUSIÓN: A pesar del recelo tradicional, la mayoría (70%) de los tumores lipomatosos profundos son lipomas benignos. Algunas características, como los tumores de menos de 5 cm y aquellos ubicados fuera de las extremidades inferiores sin características sospechosas por RNM, indican que los tumores casi nunca son ALT. Los tumores con esas características pueden tratarse de manera segura y con solvencia fuera de los centros de sarcomas terciarios. En casos seleccionados, puede ser útil la prueba genética MDM2 en la biopsia.

Assessment of the platelet-derived growth factor receptor alpha antibody olaratumab in a panel of patient-derived soft tissue sarcoma xenografts.

BACKGROUND: Soft tissue sarcoma (STS) comprises a family of rare, heterogeneous tumors of mesenchymal origin. Single-agent doxorubicin remains the first-line standard-of-care treatment for advanced and inoperable STS, but response rates are only around 15%. In 2016, phase Ib/II clinical trial results reported an overall survival benefit of 11.8 months when combining doxorubicin and the platelet-derived growth factor receptor alpha (PDGFRA)-directed antibody olaratumab compared to doxorubicin alone, without providing a scientific rationale for such unprecedented therapeutic effect. We decided to evaluate the efficacy of olaratumab in a panel of STS patient-derived xenografts (PDX). METHODS: NMRI nu/nu mice were bilaterally transplanted with tumor tissue of patient-derived xenograft models expressing PDGFRA, including models of leiomyosarcoma (UZLX-STS22), malignant peripheral nerve sheath tumor (UZLX-STS39), myxofibrosarcoma (UZLX-STS59) and undifferentiated pleomorphic sarcoma (UZLX-STS84). Mice were randomly divided into four different treatment groups: (1) control, (2) doxorubicin (3 mg/kg once weekly), (3) anti-PDGFRA [olaratumab (60 mg/kg twice weekly) + mouse anti-PDGFRA antibody 1E10 (20 mg/kg twice weekly)] and (4) the combination of doxorubicin and anti-PDGFRA (same dose/schedule as in the single treatment arms). Tumor volume, histopathology and Western blotting were used to assess treatment efficacy. RESULTS: Anti-PDGFRA treatment as a single agent did not reduce tumor growth and did not result in significant anti-proliferative or pro-apoptotic activity. Combining doxorubicin and anti-PDGFRA did not reduce tumor burden, though a mild inhibition of proliferation was observed in UZLX-STS39 and -STS59. A pro-apoptotic effect was observed in all models except UZLX-STS22. Antitumor effects on histology were not significantly different comparing doxorubicin and the combination treatment. Moreover, anti-PDGFRA treatment, both as a single agent as well as combined with doxorubicin, did not result in inhibition of the downstream MAPK and PI3K/AKT signaling pathways. CONCLUSIONS: We were not able to demonstrate significant antitumor effects of anti-PDGFRA treatment in selected STS PDX models, neither alone nor in combination with doxorubicin. This is in line with the very recent results of the phase III clinical trial NCT02451943 ANNOUNCE, which did not confirm the clinical benefit of olaratumab in combination with doxorubicin over single agent doxorubicin.

Surgery Tutor for Computational Assessment of Technical Proficiency in Soft-Tissue Tumor Resection in a Simulated Setting.

BACKGROUND: In competency-based medical education, progression between milestones requires reliable and valid methods of assessment. Surgery Tutor is an open-source motion tracking platform developed to objectively assess technical proficiency during open soft-tissue tumor resections in a simulated setting. The objective of our study was to provide evidence in support of construct validity of the scores obtained by Surgery Tutor. We hypothesized that Surgery Tutor would discriminate between novice, intermediate, and experienced operators. METHODS: Thirty participants were assigned to novice, intermediate, or experienced groups, based on the number of prior soft-tissue resections performed. Each participant resected 2 palpable and 2 nonpalpable lesions from a soft-tissue phantom. Surgery Tutor was used to track hand and instrument motions, number of tumor breaches, and time to perform each resection. Mass of excised specimens and margin status were also recorded. RESULTS: Surgery Tutor scores demonstrated "moderate" to "good" internal structure (test-retest reliability) for novice, intermediate, and experienced groups (interclass correlation coefficient = 0.596, 0.569, 0.737; p < 0.001). Evidence in support of construct validity (consequences) was demonstrated by comparing scores of novice, intermediate, and experienced participantsfor number of hand and instrument motions (690 ± 190, 597 ± 169, 469 ± 110; p < 0.001), number of tumor breaches (29 ± 34, 16 ± 11, 9 ± 6; p < 0.001), time per resection (677 ± 331 seconds, 561 ± 210 seconds, 449 ± 148 seconds; p < 0.001), mass of completely excised specimens (22 ± 7g, 21 ± 11g, 17 ± 6 g; p = 0.035), and rate of positive margin (68%, 50%, 28%; p < 0.001). There was "strong" and "moderate" relationships between motion scores and Objective Structured Assessment of Technical Skill scores, and time per resection and Objective Structured Assessment of Technical Skill scores respectively (r = -0.60, p < 0.001; r = -0.54, p < 0.001). CONCLUSION: Surgery Tutor scores demonstrate evidenceof construct validity with regards to good internal structure, consequences, and relationship to other variables in the assessment of technical proficiency duringopen soft-tissue tumor resections in a simulated setting. Utilization of Surgery Tutor can provide formative feedback and objective assessment of surgical proficiency in a simulated setting.

MRI assessment of surrounding tissues in soft-tissue sarcoma during neoadjuvant chemotherapy can help predicting response and prognosis.

OBJECTIVES: To determine if changes in surrounding tissues of soft-tissue sarcomas (STS) evaluated by MRI during neoadjuvant chemotherapy (NAC) are associated with the histological response and satellite tumorous cells beyond the pseudocapsule on surgical specimen, disease-free survival (DFS) and overall survival (OS). METHODS: Fifty-seven adult patients with locally advanced high-grade STS of extremities and trunk wall were included in this single-centre retrospective study. All were uniformly treated by 5-6 cycles of anthracycline-based NAC, curative surgery and adjuvant radiotherapy and had available MRI with a gadolinium-chelates administration at baseline and after 2 cycles. Thirty-seven patients also had a pre-operative MRI. Two senior radiologists evaluated MRI growth pattern, oedema, contrast-enhanced oedema, aponeurotic enhancement, and their qualitative changes during NAC. An expert pathologist reviewed all surgical specimens. A good histological response was defined as <10% viable cells. Associations with pathological findings were estimated with Fisher and Chi-square tests and multivariate analysis with binary logistic regression. Survival analyses included log-rank tests. RESULTS: Forty-two patients had poor responses and 25 had satellite tumorous cells on surgical specimen. Changes in surrounding oedema and in contrast-enhanced oedema were associated with responses (p = 0.008 and 0.011, respectively). Diffuse infiltrative growth pattern (IGP) on baseline MRI, changes in margin definition and in contrast-enhanced oedema at early evaluation were associated with satellite tumorous cells (p = 0.039, 0.011 and 0.009, respectively). Diffuse IGP on baseline MRI and stable or increased oedema during treatment were predictors of DFS (p = 0.009 and 0.040, respectively). CONCLUSION: Surrounding tissues of STS during NAC should be carefully evaluated as they may steer treatment efficacy and patient prognosis.

Skin and Soft Tissue Surgery in the Office Versus Operating Room Setting: An Analysis Based on Individual-Level Medicare Data.

BACKGROUND: The relative volume of skin and soft tissue excision and reconstructive procedures performed in the outpatient office versus facility (ambulatory surgical center or hospital) differs by specialty, and has major implications for quality of care, outcomes, development of guidelines, resident education, health care economics, and patient perception. OBJECTIVE: To assess the relative volume of surgical procedures performed in each setting (office vs ambulatory surgery center [ASC]/hospital) by dermatologists and nondermatologists. METHODS: A cross-sectional analytical study was performed using the Medicare public use file (PUF) for 2014, which includes every patient seen in an office, ASC, or hospital in the United States billed to Medicare part B. Data were divided by physician specialty and setting. RESULT: A total of 9,316,307 individual encounters were included in the Medicare PUF. Dermatologists account for 195,001 (2.1%) of the total. Dermatologists were more likely to perform surgical procedures in an office setting only (odds ratio 5.48 [95% confidence interval 5.05-5.95], p < .0001) than other specialists in aggregate. CONCLUSION: More than 90% of surgical procedures are performed in an office setting, and dermatologists are more than 5 times as likely as other specialists to operate in an office setting.

[Radiotherapy for soft tissue sarcomas: Technical evolution and impact on clinical benefit]. / Radiothérapie des sarcomes des tissus mous des membres : évolution technique et impact sur le bénéfice clinique.

The standard treatment for extremity soft tissue sarcomas is based on the association of surgery and radiotherapy. This strategy allows local control improvement with the risk of increased toxicity. There is therefore a growing interest to identify those patients who will benefit from radiotherapy and those who will have the same local control with surgery alone. Furthermore, the development of toxicity has been correlated with the extension of the irradiated volume and the volume receiving high doses. Technological development as intensity modulated radiotherapy and image-guided radiotherapy allows limited irradiated volume improving the protection of the organs at risk leading to clinical benefit improvement. Moreover, efforts are being done to improve local control for the patients at high risk of local relapse. In this paper, we discuss all these mentioned aspects.

Patient factors affecting the Toronto extremity salvage score following limb salvage surgery for bone and soft tissue tumors.

BACKGROUND AND OBJECTIVES: The Toronto extremity salvage score (TESS) assesses physical function following limb salvage for bone and soft tissue sarcoma. In 2012, Clayer et al. showed increasing age affects the TESS score in normal individuals. The purpose of this study was to investigate what other patient factors affect outcome? METHODS: We reviewed the TESS scores, age, sex, BMI, diagnosis, smoking status, and social deprivation score of patients who have undergone limb salvage in our unit. Data were extracted from our tumor database and reviewed. Statistical analysis was performed using Wilcoxon pairwise test and linear regression analysis. RESULTS: Four hundred and ninety-eight TESS scores were found for 198 patients. Data were analyzed separating upper limb (UL) and lower limb (LL) tumors. In the UL group, being female (P = 0.01) and having a bone lesion (P < 0.001) were associated with a lower TESS score. In the LL group, being female (P = 0.04), increasing age (P = 0.002), having a bone lesion (P < 0.001), increasing BMI (P < 0.001), and smoking (P = 0.005) were associated with a lower TESS score. CONCLUSIONS: Analysis has shown that female sex, increasing age and BMI, smoking and having a bone lesion have an adverse effect on physical function following limb salvage, as indicated by the mean TESS score. J. Surg. Oncol. 2016;113:804-810. © 2016 Wiley Periodicals, Inc.