Sarcoma http://www.hindawi.com The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . All rights reserved. Rhabdomyosarcoma: Advances in Molecular and Cellular Biology Tue, 01 Sep 2015 13:55:37 +0000 http://www.hindawi.com/journals/sarcoma/2015/232010/ Rhabdomyosarcoma (RMS) is the most common soft tissue malignancy in childhood and adolescence. The two major histological subtypes of RMS are alveolar RMS, driven by the fusion protein PAX3-FKHR or PAX7-FKHR, and embryonic RMS, which is usually genetically heterogeneous. The prognosis of RMS has improved in the past several decades due to multidisciplinary care. However, in recent years, the treatment of patients with metastatic or refractory RMS has reached a plateau. Thus, to improve the survival rate of RMS patients and their overall well-being, further understanding of the molecular and cellular biology of RMS and identification of novel therapeutic targets are imperative. In this review, we describe the most recent discoveries in the molecular and cellular biology of RMS, including alterations in oncogenic pathways, miRNA (miR), in vivo models, stem cells, and important signal transduction cascades implicated in the development and progression of RMS. Furthermore, we discuss novel potential targeted therapies that may improve the current treatment of RMS. Xin Sun, Wei Guo, Jacson K. Shen, Henry J. Mankin, Francis J. Hornicek, and Zhenfeng Duan Copyright © 2015 Xin Sun et al. All rights reserved. Clinical Epidemiology of Low-Grade and Dedifferentiated Osteosarcoma in Norway during 1975 and 2009 Sun, 30 Aug 2015 08:07:58 +0000 http://www.hindawi.com/journals/sarcoma/2015/917679/ Purpose. To describe epidemiological, clinical characteristics and treatment outcomes of low-grade osteosarcoma (LGOS), including dedifferentiated osteosarcoma (DLGOS). Method. We analysed a nationwide cohort comprised of patients with histologically verified LGOS and DLGOS between 1975 and 2009, based on registry sources supplemented with clinical records from hospitals involved in sarcoma management. Results. Fifty-four patients were identified, 12 of whom had DLGOS. The annual incidence for all patients was 0.3 per million, with the peak incidence in the third decade of the life. Fifteen patients experienced local relapses during follow-up and ten developed metastatic diseases, including three at primary diagnosis. Patients with DLGOS dominated the metastatic relapse group. The five-year sarcoma-specific survival rate was 91%, with no documented improvement over time. Free margin following surgical resection of the primary tumour had a positive impact on survival. As expected, both local relapse and metastasis during follow-up were associated with an unfavourable outcome. Radiotherapy predicted poor survival due to the selection of high-risk patients in need of such treatment. Neither higher age nor axial tumour localisation was adverse prognostic factors. Conclusion. LGOS has an excellent prognosis when surgically resected with a free margin; however, LGOS has the potential to dedifferentiate and metastasize with a poor outcome. Kjetil Berner, Tom Børge Johannesen, and Øyvind S. Bruland Copyright © 2015 Kjetil Berner et al. All rights reserved. Intraoperative Radiotherapy in the Management of Locally Recurrent Extremity Soft Tissue Sarcoma Sun, 09 Aug 2015 09:41:20 +0000 http://www.hindawi.com/journals/sarcoma/2015/913565/ Purpose. To investigate the efficacy and morbidity of limb-sparing surgery with intraoperative radiotherapy (IORT) for patients with locally recurrent extremity soft tissue sarcoma (ESTS). Methods and Materials. Twenty-six consecutively treated patients were identified in a single institution retrospective analysis of patients with locally recurrent ESTS treated with IORT following salvage limb-sparing resection from May 2000 to July 2011. Fifteen (58%) patients received external beam radiotherapy (EBRT) prior to recurrence (median dose 63 Gy), while 11 (42%) patients received EBRT following IORT (median dose 52 Gy). The Kaplan-Meier product limit method was used to estimate disease control and survival and subsets were compared using a log rank statistic, Cox’s regression model was used to determine independent predictors of disease outcome, and toxicity was reported according to CTCAE v4.0 guidelines. Results. With a median duration of follow-up from surgery and IORT of 34.9 months (range: 4 to 139 mos.), 10 patients developed a local recurrence with 4 subsequently undergoing amputation. The 5-year estimate for local control (LC) was 58% (95% CI: 36–75%), for amputation-free was 81% (95% CI: 57–93%), for metastasis-free control (MFC) was 56% (95% CI: 31–75%), for disease-free survival (DFS) was 35% (95% CI: 17–54%), and for overall survival (OS) was 50% (95% CI: 24–71%). Prior EBRT did not appear to influence disease control (LC, ; MFC, ) or survival (DFS, ; OS, ). Grade 3 or higher acute and late toxicities were reported for 6 (23%) and 8 (31%) patients, respectively. The frequency of both acute and late grade 3 or higher toxicities occurred equally between patients who received EBRT prior to or after IORT. Conclusions. IORT in combination with oncologic resection of recurrent ESTS yields good rates of local control and limb-salvage with acceptable morbidity. Within the limitations of small subsets, these data suggest that prior EBRT does not significantly influence disease control or toxicity. Christopher L. Tinkle, Vivian Weinberg, Steve E. Braunstein, Rosanna Wustrack, Andrew Horvai, Thierry Jahan, Richard J. O’Donnell, and Alexander R. Gottschalk Copyright © 2015 Christopher L. Tinkle et al. All rights reserved. Whole Lung Irradiation in Adults with Metastatic Ewing Sarcoma: Practice Patterns and Implications for Treatment Thu, 25 Jun 2015 09:22:53 +0000 http://www.hindawi.com/journals/sarcoma/2015/591698/ Background. Whole lung irradiation (WLI) is a standard treatment component for children with metastatic Ewing Sarcoma (ES), but data on WLI for adults are sparse. Design. An email survey was sent to expert sarcoma-dedicated oncologists worldwide: An adult with excellent performance status presents with primary ES in the leg and multiple pulmonary metastases. The patient achieves complete radiographic response after chemotherapy and resection of the primary. Would you give bilateral WLI to (1) this adult patient?, (2) this patient if 20 years old (yo)?, (3) this patient if 45 yo?, or (4) this patient if 60 yo? Results. 38 experts responded, including 24 adult, 1 adolescent young adult, and 13 pediatric oncologists. 63%, 63%, 62%, and 50% of respondents offered WLI to the adult, 20-year-old, 45-year-old, and 60-year-old, respectively. Pediatric oncologists more likely endorsed WLI across all ages including the adult (), 20-year-old (), 45-year-old (), and 60-year-old (). There were no significant differences between medical and radiation oncologists or between European/Australian and American providers. Conclusions. Almost two-thirds of experts surveyed supported WLI for adults with metastatic ES up to age 45 and half supported WLI for a 60-year-old. Continued collaboration across adult and pediatric oncology is needed to define evidence-based strategies across the age spectrum. Shyam K. Tanguturi, Suzanne George, Karen J. Marcus, George D. Demetri, and Elizabeth H. Baldini Copyright © 2015 Shyam K. Tanguturi et al. All rights reserved. Corrigendum to “Sarcoma Immunotherapy: Past Approaches and Future Directions” Tue, 09 Jun 2015 07:19:24 +0000 http://www.hindawi.com/journals/sarcoma/2015/259817/ S. P. D’Angelo, W. D. Tap, G. K. Schwartz, and R. D. Carvajal Copyright © 2015 S. P. D’Angelo et al. All rights reserved. Mesenchymal Chondrosarcoma in Children and Young Adults: A Single Institution Retrospective Review Wed, 03 Jun 2015 13:03:11 +0000 http://www.hindawi.com/journals/sarcoma/2015/608279/ Background. Mesenchymal chondrosarcoma is an aggressive, uncommon histologic entity arising in bone and soft tissues. We reviewed our institutional experience with this rare diagnosis. Methods. We conducted a retrospective chart review on patients with mesenchymal chondrosarcoma over a 24-year period. Clinicopathologic and radiographic features were reviewed. Results. Twelve patients were identified. Nine were females; median age was 14.5 years (1.2–19.7 years). The most common site was the head/neck (7/12). Disease was localized in 11/12 patients (one with lung nodules). Six with available tissue demonstrated NCOA2 rearrangement by FISH. Six underwent upfront surgical resection, and six received neoadjuvant therapy (2 chemotherapy alone and 4 chemotherapy and radiation). All patients received adjuvant chemotherapy (most commonly ifosfamide/doxorubicin) and/or radiation (median dose 59.4 Gy). At a median follow-up of 4.8 years, 5-year disease-free survival and overall survival were 68.2% (95% CI 39.8%, 96.6%) and 88.9% (95% CI 66.9%, 100%). Two patients had distant recurrences at 15 and 42 months, respectively. Conclusion. Aggressive surgical resection of mesenchymal chondrosarcoma with chemoradiotherapy yields excellent local control and may reduce likelihood of late recurrence. Characterization of downstream targets of the HEY1-NCOA2 fusion protein, xenograft models, and drug screening are needed to identify novel therapeutic strategies. Michael W. Bishop, Jessica M. Somerville, Armita Bahrami, Sue C. Kaste, Rodrigo B. Interiano, Jianrong Wu, Shenghua Mao, Frederick A. Boop, Regan F. Williams, Alberto S. Pappo, and Sandeep Samant Copyright © 2015 Michael W. Bishop et al. All rights reserved. Management Strategies in Advanced Uterine Leiomyosarcoma: Focus on Trabectedin Mon, 18 May 2015 14:18:36 +0000 http://www.hindawi.com/journals/sarcoma/2015/704124/ The treatment of advanced uterine leiomyosarcomas (U-LMS) represents a considerable challenge. Radiological diagnosis prior to hysterectomy is difficult, with the diagnosis frequently made postoperatively. Whilst a total abdominal hysterectomy is the cornerstone of management of early disease, the role of routine adjuvant pelvic radiotherapy and adjuvant chemotherapy is less clear, since they may improve local tumor control in high risk patients but are not associated with an overall survival benefit. For recurrent or disseminated U-LMS, cytotoxic chemotherapy remains the mainstay of treatment. There have been few active chemotherapy drugs approved for advanced disease, although newer drugs such as trabectedin with its pleiotropic mechanism of actions represent an important addition to the standard front-line systemic therapy with doxorubicin and ifosfamide. In this review, we outline the therapeutic potential and in particular the emerging evidence-based strategy of therapy with trabectedin in patients with advanced U-LMS. Frédéric Amant, Domenica Lorusso, Alexander Mustea, Florence Duffaud, and Patricia Pautier Copyright © 2015 Frédéric Amant et al. All rights reserved. Phase II Trial of Gemcitabine and Docetaxel with Bevacizumab in Soft Tissue Sarcoma Thu, 14 May 2015 12:42:56 +0000 http://www.hindawi.com/journals/sarcoma/2015/532478/ Gemcitabine (G) and docetaxel (D) are commonly used to treat recurrent/metastatic soft tissue sarcoma. This study tested the hypothesis that outcomes would be improved by addition of bevacizumab (B). The initial design was randomized double-blind trial of G + D + B versus G + D + placebo. Due to slow accrual this was modified to single-arm open-label G + D + B. Eligible patients had diagnosis of leiomyosarcoma, pleomorphic undifferentiated sarcoma, pleomorphic liposarcoma, or angiosarcoma. Treatment was B 15 mg/kg on d1, G 900 mg/m2 on d1 and d8, and D 75 mg/m2 on d8, q21d. Primary endpoint was progression-free survival (PFS) at 6 months and would be met if ≥17 patients were progression-free at 6 m. Secondary endpoints are response rate, PFS at 3 m, overall survival, and toxicity. Of 44 patients enrolled, 35 were treated with GDB and evaluable for safety and efficacy. Median age was 55, 50% male, most ECOG 0. Toxicity is mostly myelosuppression with one deep vein thrombosis and one small bowel perforation possibly related to B. There were 17 partial responses (49%) by RECIST 1.1. Among 35 patients, the number who remained on study and progression-free was 24 at 3 m and 15 at 6 m. 9 withdrew prior to 6 m for reasons other than toxicity or progression. PFS at 6 m was 65% (95% CI: 51–85%). The primary endpoint of 6 m PFS was not met due to censoring of patients who withdrew. However PFS at 3 m (76%) was promising and response rate was higher than expected from G + D. Mark A. Dickson, David R. D’Adamo, Mary L. Keohan, Sandra P. D’Angelo, Richard D. Carvajal, Mrinal M. Gounder, Robert G. Maki, Li-Xuan Qin, Robert A. Lefkowitz, Olivia R. McKennon, Catherine M. Hirst, Gary K. Schwartz, and William D. Tap Copyright © 2015 Mark A. Dickson et al. All rights reserved. Medication Exposures and Subsequent Development of Ewing Sarcoma: A Review of FDA Adverse Event Reports Thu, 07 May 2015 16:52:37 +0000 http://www.hindawi.com/journals/sarcoma/2015/948159/ Background. Ewing sarcoma family of tumors (ESFT) are rare but deadly cancers of unknown etiology. Few risk factors have been identified. This study was undertaken to ascertain any possible association between exposure to therapeutic drugs and ESFT. Methods. This is a retrospective, descriptive study. A query of the FDA Adverse Event Reporting System (FAERS) was conducted for all reports of ESFT, January 1, 1998, through December 31, 2013. Report narratives were individually reviewed for patient characteristics, underlying conditions and drug exposures. Results. Over 16 years, 134 ESFT reports were identified, including 25 cases of ESFT following therapeutic drugs and biologics including immunosuppressive agents and hormones. Many cases were confounded by concomitant medications and other therapies. Conclusions. This study provides a closer look at medication use and underlying disorders in patients who later developed ESFT. While this study was not designed to demonstrate any clear causative association between ESFT and prior use of a single product or drug class, many drugs were used to treat immune-related disease and growth or hormonal disturbances. Further studies may be warranted to better understand possible immune or neuroendocrine abnormalities or exposure to specific classes of drugs that may predispose to the later development of ESFT. Judith U. Cope, Gregory H. Reaman, and Joseph M. Tonning Copyright © 2015 Judith U. Cope et al. All rights reserved. The Use of Radiation Therapy in Well-Differentiated Soft Tissue Sarcoma of the Extremities: An NCDB Review Thu, 07 May 2015 12:44:57 +0000 http://www.hindawi.com/journals/sarcoma/2015/186581/ Objective. This study investigated patterns of utilization of radiation therapy (RT) and correlated this with overall survival by assessing patients with well-differentiated soft tissue sarcoma of the extremity (STS-E) in the National Cancer Database (NCDB). Methods. All patients diagnosed with well-differentiated STS-E between 1998 and 2006 were identified in the NCDB. Patients were stratified by use of surgery alone versus use of adjuvant RT after surgery and analyzed using multivariate analysis, Kaplan-Meier analysis, and propensity matching. Results. 2113 patients with well-differentiated STS-E were identified in the NCDB for inclusion with a mean follow-up time of 74 months. 69% of patients were treated with surgery alone, while 26% were treated with surgery followed by adjuvant RT. Patients undergoing amputation were less likely to receive adjuvant RT. There was no difference in overall survival between patients with well-differentiated STS treated with surgery alone and those patients who received adjuvant RT. Conclusions. In the United States, adjuvant RT is being utilized in a quarter of patients being treated for well-differentiated STS-E. While the use of adjuvant RT may be viewed as a means to facilitate limb salvage, this large national database review confirms no survival benefit, regardless of tumor size or margin status. Alexander L. Lazarides, William C. Eward, Paul J. Speicher, Chun-Han Hou, Daniel P. Nussbaum, Cindy Green, Dan G. Blazer III, David G. Kirsch, and Brian E. Brigman Copyright © 2015 Alexander L. Lazarides et al. All rights reserved. Cured of Primary Bone Cancer, But at What Cost: A Qualitative Study of Functional Impairment and Lost Opportunities Thu, 09 Apr 2015 08:36:25 +0000 http://www.hindawi.com/journals/sarcoma/2015/484196/ Purpose. Our study aims to explore how former cancer patients experience physical and psychosocial late effects 3–7 years after they underwent treatment for primary bone sarcoma in the hip/pelvic region. A qualitative, phenomenological, and hermeneutic design was applied. Methods. Sarcoma survivors () previously treated at Oslo University Hospital, Norwegian Radium Hospital were selected to participate. In-depth and semistructured interviews were conducted. The interviews were analysed using inductive thematic analysis. Results. The participants reported that the late effects had three core spheres of impact: “their current daily life,” “their future opportunities,” and “their identity.” They expressed negative changes in activity, increased dependence on others, and exclusion from participation in different areas. Their daily life, work, sports activities, and social life were all affected. Several of their experiences are similar to those described by people with functional impairment or disability. Conclusion. Patients cured of bone cancer in the hip/pelvic region pay a significant price in terms of functional impairment, practical challenges, exclusion from important aspects of life, and loss of previous identity. It is important to appreciate this in order to help bone cancer survivors who struggle to reorient their life and build a secure new identity. Lena Fauske, Oyvind S. Bruland, Ellen Karine Grov, and Hilde Bondevik Copyright © 2015 Lena Fauske et al. All rights reserved. Myeloablative Chemotherapy with Autologous Stem Cell Transplant for Desmoplastic Small Round Cell Tumor Tue, 07 Apr 2015 09:19:57 +0000 http://www.hindawi.com/journals/sarcoma/2015/269197/ Desmoplastic small round cell tumor (DSRCT), a rare, aggressive neoplasm, has a poor prognosis. In this prospective study, we evaluated the role of myeloablative chemotherapy, followed by autologous stem cell transplant in improving survival in DSRCT. After high-dose induction chemotherapy and surgery, 19 patients with chemoresponsive DSRCT underwent autologous stem cell transplant. Myeloablative chemotherapy consisted of carboplatin (400–700 mg/m2/day for 3 days) + thiotepa (300 mg/m2/day for 3 days) ± topotecan (2 mg/m2/day for 5 days). All patients were engrafted and there was no treatment-related mortality. Seventeen patients received radiotherapy to sites of prior or residual disease at a median of 12 weeks after transplant. Five-year event-free and overall survival were 11 ± 7% and 16 ± 8%, respectively. Two patients survive disease-free 16 and 19 years after transplant (both in complete remission before transplant). 14 patients had progression and died of disease at a median of 18 months following autologous transplant. These data do not justify the use of myeloablative chemotherapy with carboplatin plus thiotepa in patients with DSRCT. Alternative therapies should be considered for this aggressive neoplasm. Christopher J. Forlenza, Brian H. Kushner, Nancy Kernan, Farid Boulad, Heather Magnan, Leonard Wexler, Suzanne L. Wolden, Michael P. LaQuaglia, and Shakeel Modak Copyright © 2015 Christopher J. Forlenza et al. All rights reserved. Molecular Analysis of a Recurrent Sarcoma Identifies a Mutation in FAF1 Tue, 10 Mar 2015 10:53:25 +0000 http://www.hindawi.com/journals/sarcoma/2015/839182/ A patient presented with a recurrent sarcoma (diagnosed as leiomyosarcoma) 12 years after the removal of an initial cancer (diagnosed as extracompartmental osteosarcoma) distally on the same limb. Following surgery, the sarcoma and unaffected muscle and bone were subjected to measurements of DNA exome sequence, RNA and protein expression, and transcription factor binding. The investigation provided corroboration of the diagnosis leiomyosarcoma, as the major upregulations in this tumor comprise muscle-specific gene products and calcium-regulating molecules (calcium is an important second messenger in smooth muscle cells). A likely culprit for the disease is the point mutation S181G in FAF1, which may cause a loss of apoptotic function consecutive to transforming DNA damage. The RNA levels of genes for drug transport and metabolism were extensively skewed in the tumor tissue as compared to muscle and bone. The results suggest that the tumor represents a recurrence of a dormant metastasis from an originally misdiagnosed neoplasm. A loss of FAF1 function could cause constitutive WNT pathway activity (consistent with the downstream inductions of IGF2BP1 and E2F1 in this cancer). While the study has informed on drug transport and drug metabolism pharmacogenetics, it has fallen short of identifying a suitable target for molecular therapy. Georg F. Weber Copyright © 2015 Georg F. Weber. All rights reserved. Improvement in Overall Survival from Extremity Soft Tissue Sarcoma over Twenty Years Tue, 03 Mar 2015 11:55:56 +0000 http://www.hindawi.com/journals/sarcoma/2015/279601/ Several patient demographic factors, including marital status, have been demonstrated to have prognostic significance for survival in extremity soft tissue sarcoma (ESTS). A study population of 12,546 adult patients diagnosed with ESTS from 1991 to 2010 was identified from the SEER database, a large population-based registry, in order to determine whether overall survival had changed over this recent 20-year period. The study population was divided into three groups by year of diagnosis: 1991–1996, 1997–2003, and 2004–2010. We used the Kaplan-Meier method and Cox proportional hazards regression to assess survival differences between different demographic groups and prognostic clinical characteristics. Over the course of time, the 5-year overall survival rates have increased from 28% in the earliest time period to 62% in the latest . On multivariate analysis, the mortality rate progressively declined from the 1991–1996 group (HR: 3.02, CI: 2.78–3.29) to the 1997–2003 group (HR: 2.21, CI: 2.06–2.37), with the 2004–2010 group having the best overall survival, despite increases in the proportion of patients with tumors greater than 5 cm in size , and those presenting with metastasis . Andrew J. Jacobs, Ryan Michels, Joanna Stein, and Adam S. Levin Copyright © 2015 Andrew J. Jacobs et al. All rights reserved. Fluorescence In Situ Hybridization for MDM2 Amplification as a Routine Ancillary Diagnostic Tool for Suspected Well-Differentiated and Dedifferentiated Liposarcomas: Experience at a Tertiary Center Wed, 25 Feb 2015 13:25:50 +0000 http://www.hindawi.com/journals/sarcoma/2015/812089/ Background. The assessment of MDM2 gene amplification by fluorescence in situ hybridization (FISH) has become a routine ancillary tool for diagnosing atypical lipomatous tumor (ALT)/well-differentiated liposarcoma and dedifferentiated liposarcoma (WDL/DDL) in specialist sarcoma units. We describe our experience of its utility at our tertiary institute. Methods. All routine histology samples in which MDM2 amplification was assessed with FISH over a 2-year period were included, and FISH results were correlated with clinical and histologic findings. Results. 365 samples from 347 patients had FISH for MDM2 gene amplification. 170 were positive (i.e., showed MDM2 gene amplification), 192 were negative, and 3 were technically unsatisfactory. There were 122 histologically benign cases showing a histology:FISH concordance rate of 92.6%, 142 WDL/DDL (concordance 96.5%), and 34 cases histologically equivocal for WDL (concordance 50%). Of 64 spindle cell/pleomorphic neoplasms (in which DDL was a differential diagnosis), 21.9% showed MDM2 amplification. Of the cases with discrepant histology and FISH, all but 3 had diagnoses amended following FISH results. For discrepancies of benign histology but positive FISH, lesions were on average larger, more frequently in “classical” (intra-abdominal or inguinal) sites for WDL/DDL and more frequently core biopsies. Discrepancies of malignant histology but negative FISH were smaller, less frequently in “classical” sites but again more frequently core biopsies. Conclusions. FISH has a high correlation rate with histology for cases with firm histologic diagnoses of lipoma or WDL/DDL. It is a useful ancillary diagnostic tool in histologically equivocal cases, particularly in WDL lacking significant histologic atypia or DDL without corresponding WDL component, especially in larger tumors, those from intra-abdominal or inguinal sites or core biopsies. There is a significant group of well-differentiated adipocytic neoplasms which are difficult to diagnose on morphology alone, in which FISH for MDM2 amplification is diagnostically contributory. Khin Thway, Jayson Wang, John Swansbury, Toon Min, and Cyril Fisher Copyright © 2015 Khin Thway et al. All rights reserved. Prognostic Factors and Treatment Results of High-Grade Osteosarcoma in Norway: A Scope Beyond the “Classical” Patient Tue, 17 Feb 2015 11:32:14 +0000 http://www.hindawi.com/journals/sarcoma/2015/516843/ Purpose. A retrospective study of prognostic factors and treatment outcome of osteosarcoma (OS) during modern chemotherapy era with focus on patients with primary metastatic disease, nonextremity localisation, or age >40 years (nonclassical OS). Methods. A nationwide cohort, comprising 424 high-grade Norwegian bone OS patients, was based on registry sources supplemented with clinical records from hospitals involved in sarcoma management between 1975 and 2009. Results. Only 48% were younger patients with tumour in the extremities and without metastasis at diagnosis (classical OS). A considerable discrepancy in survival between classical and nonclassical OS was observed: 61% versus 26% 10-year sarcoma specific survival. Twice as many of the former received both adequate surgery and chemotherapy compared to the latter. This could only partly explain the differences in survival due to inherent chemoresistance in primary metastatic disease and a higher rate of local relapse among patients with axial tumours. Metastasis at diagnosis, increased lactate dehydrogenase, age > 40 years, and tumour size above median value were all adverse prognostic factors for overall survival. Conclusion. We confirm a dramatic difference in outcome between classical and nonclassical high-grade OS patients, but treatment variables could only partly explain the dismal outcome of the latter. Kjetil Berner, Kirsten Sundby Hall, Odd R. Monge, Harald Weedon-Fekjær, Olga Zaikova, and Øyvind S. Bruland Copyright © 2015 Kjetil Berner et al. All rights reserved. Intercalary Reconstruction after Wide Resection of Malignant Bone Tumors of the Lower Extremity Using a Composite Graft with a Devitalized Autograft and a Vascularized Fibula Mon, 16 Feb 2015 11:31:11 +0000 http://www.hindawi.com/journals/sarcoma/2015/861575/ Introduction. Although several intercalary reconstructions after resection of a lower extremity malignant bone tumor are reported, there are no optimal methods which can provide a long-term reconstruction with fewest complications. We present the outcome of reconstruction using a devitalized autograft and a vascularized fibula graft composite. Materials and Methods. We conducted a retrospective review of 11 patients (7 males, 4 females; median age 27 years) undergoing reconstruction using a devitalized autograft (pasteurization (), deep freezing ()) and a vascularized fibula graft composite for lower extremity malignant bone tumors (femur (), tibia ()). Results. The mean period required for callus formation and bone union was 4.4 months and 9.9 months, respectively. Four postoperative complications occurred in 3 patients: 2 infections (1 pasteurized autograft, 1 frozen autograft) and 1 fracture and 1 implant failure (both in pasteurized autografts). Graft removal was required in 2 patients with infections. The mean MSTS score was 81% at last follow-up. Conclusions. Although some complications were noted in early cases involving a pasteurized autograft, our novel method involving a combination of a frozen autograft with a vascularized fibula graft and rigid fixation with a locking plate may offer better outcomes than previously reported allografts or devitalized autografts. Koichi Ogura, Shimpei Miyamoto, Minoru Sakuraba, Tomohiro Fujiwara, Hirokazu Chuman, and Akira Kawai Copyright © 2015 Koichi Ogura et al. All rights reserved. Wiki-Based Clinical Practice Guidelines for the Management of Adult Onset Sarcoma: A New Paradigm in Sarcoma Evidence Mon, 16 Feb 2015 08:46:09 +0000 http://www.hindawi.com/journals/sarcoma/2015/614179/ In 2013 Australia introduced Wiki-based Clinical Practice Guidelines for the Management of Adult Onset Sarcoma. These guidelines utilized a customized MediaWiki software application for guideline development and are the first evidence-based guidelines for clinical management of sarcoma. This paper presents our experience with developing and implementing web-based interactive guidelines and reviews some of the challenges and lessons from adopting an evidence-based (rather than consensus-based) approach to clinical sarcoma guidelines. Digital guidelines can be easily updated with new evidence, continuously reviewed and widely disseminated. They provide an accessible method of enabling clinicians and consumers to access evidence-based clinical practice recommendations and, as evidenced by over 2000 views in the first four months after release, with 49% of those visits being from countries outside of Australia. The lessons learned have relevance to other rare cancers in addition to the international sarcoma community. S. J. Neuhaus, D. Thomas, J. Desai, C. Vuletich, J. von Dincklage, and I. Olver Copyright © 2015 S. J. Neuhaus et al. All rights reserved. Identifying the Prevalence, Trajectory, and Determinants of Psychological Distress in Extremity Sarcoma Thu, 12 Feb 2015 11:48:52 +0000 http://www.hindawi.com/journals/sarcoma/2015/745163/ Objective. Extremity sarcoma (ES) is a rare cancer that presents with unique challenges. This study was performed to identify the prevalence, trajectory, and determinants of distress and characterise sources of stress in this cohort. Methods. Consecutive patients with ES were prospectively recruited between May 2011 and December 2012. Questionnaires were administered during initial diagnosis and then six months and one year after surgery. Results. Distress was reported by about a third of our cohort and associated with poorer physical function, poorer quality of life, and pain. In addition to fears regarding mortality and life role changes, the most common sources of stress were centered on dissatisfaction with the healthcare system, such as frustrations with a lack of communication with the hospital regarding appointments and lack of education regarding management and outcomes. Conclusions. Psychological distress presents early in the cancer journey and persists up to one year after surgery. Distress is associated with negative outcomes. Active screening and effective interventions are necessary to improve outcomes. Sources of stress have been identified that may be amenable to targeted interventions. Melissa H. Tang, David J. Castle, and Peter F. M. Choong Copyright © 2015 Melissa H. Tang et al. All rights reserved. Analysis of the Intratumoral Adaptive Immune Response in Well Differentiated and Dedifferentiated Retroperitoneal Liposarcoma Thu, 29 Jan 2015 13:05:56 +0000 http://www.hindawi.com/journals/sarcoma/2015/547460/ Treatment options are limited in well differentiated (WD) and dedifferentiated (DD) retroperitoneal liposarcoma. We sought to study the intratumoral adaptive immune response and explore the potential feasibility of immunotherapy in this disease. Tumor-infiltrating lymphocytes (TILs) were isolated from fresh surgical specimens and analyzed by flow cytometry for surface marker expression. Previously reported immune cell aggregates known as tertiary lymphoid structures (TLS) were further characterized by immunohistochemistry. In all fresh tumors, TILs were found. The majority of TILs were CD4 T cells; however cytotoxic CD8 T cells were also seen (average: 20% of CD3 T cells). Among CD8 T cells, 65% expressed the immune checkpoint molecule PD-1. Intratumoral TLS may be sites of antigen presentation as DC-LAMP positive, mature dendritic cells were found juxtaposed next to CD4 T cells. Clinicopathologic correlation, however, demonstrated that presence of TLS was associated with worse recurrence-free survival in WD disease and worse overall survival in DD disease. Our data suggest that an adaptive immune response is present in WD/DD retroperitoneal liposarcoma but may be hindered by TLS, among other possible microenvironmental factors; further investigation is needed. Immunotherapy, including immune checkpoint blockade, should be evaluated as a treatment option in this disease. William W. Tseng, Shruti Malu, Minying Zhang, Jieqing Chen, Geok Choo Sim, Wei Wei, Davis Ingram, Neeta Somaiah, Dina C. Lev, Raphael E. Pollock, Gregory Lizée, Laszlo Radvanyi, and Patrick Hwu Copyright © 2015 William W. Tseng et al. All rights reserved. Assessment of Objective Ambulation in Lower Extremity Sarcoma Patients with a Continuous Activity Monitor: Rationale and Validation Thu, 25 Dec 2014 00:10:06 +0000 http://www.hindawi.com/journals/sarcoma/2014/947082/ In addition to patient reported outcome measures, accelerometers may provide useful information on the outcome of sarcoma patients treated with limb salvage. The StepWatch (SW) Activity Monitor (SAM) is a two-dimensional accelerometer worn on the ankle that records an objective measure of walking performance. The purpose of this study was to validate the SW in a cross-sectional population of adult patients with lower extremity sarcoma treated with limb salvage. The main outcome was correlation of total steps with the Toronto Extremity Salvage Score (TESS). In a sample of 29 patients, a mean of 12 days of SW data was collected per patient (range 6–16), with 2767 average total steps (S.D. 1867; range 406–7437). There was a moderate positive correlation between total steps and TESS . Patients with osseous tumors walked significantly less than those with soft tissue sarcoma (1882 versus 3715, ). This study supports the validity of the SAM as an activity monitor for the objective assessment of real world physical function in sarcoma patients. Kenneth R. Gundle, Stephanie E. Punt, and Ernest U. Conrad III Copyright © 2014 Kenneth R. Gundle et al. All rights reserved. Stereotactic Body Radiotherapy for Metastatic and Recurrent Ewing Sarcoma and Osteosarcoma Tue, 09 Dec 2014 00:10:13 +0000 http://www.hindawi.com/journals/sarcoma/2014/418270/ Background. Radiotherapy has been utilized for metastatic and recurrent osteosarcoma and Ewing sarcoma (ES), in order to provide palliation and possibly prolong overall or progression-free survival. Stereotactic body radiotherapy (SBRT) is convenient for patients and offers the possibility of increased efficacy. We report our early institutional experience using SBRT for recurrent and metastatic osteosarcoma and Ewing sarcoma. Methods. We reviewed all cases of osteosarcoma or ES treated with SBRT between 2008 and 2012. Results. We identified 14 patients with a total of 27 lesions from osteosarcoma or ES . The median total curative/definitive SBRT dose delivered was 40 Gy in 5 fractions (range, 30–60 Gy in 3–10 fractions). The median total palliative SBRT dose delivered was 40 Gy in 5 fractions (range, 16–50 Gy in 1–10 fractions). Two grade 2 and 1 grade 3 late toxicities occurred, consisting of myonecrosis, avascular necrosis with pathologic fracture, and sacral plexopathy. Toxicity was seen in the settings of concurrent chemotherapy and reirradiation. Conclusions. This descriptive report suggests that SBRT may be a feasible local treatment option for patients with osteosarcoma and ES. However, significant toxicity can result, and thus systematic study is warranted to clarify efficacy and characterize long-term toxicity. Lindsay C. Brown, Rachael A. Lester, Michael P. Grams, Michael G. Haddock, Kenneth R. Olivier, Carola A. S. Arndt, Peter S. Rose, and Nadia N. Laack Copyright © 2014 Lindsay C. Brown et al. All rights reserved. Can Orthopedic Oncologists Predict Functional Outcome in Patients with Sarcoma after Limb Salvage Surgery in the Lower Limb? A Nationwide Study Tue, 18 Nov 2014 00:00:00 +0000 http://www.hindawi.com/journals/sarcoma/2014/436598/ Accurate predictions of functional outcome after limb salvage surgery (LSS) in the lower limb are important for several reasons, including informing the patient preoperatively and, in some cases, deciding between amputation and LSS. This study aimed to elucidate the correlation between surgeon-predicted and patient-reported functional outcome of LSS in the Netherlands. Twenty-three patients (between six months and ten years after surgery) and five independent orthopedic oncologists completed the Toronto Extremity Salvage Score (TESS) and the RAND-36 physical functioning subscale (RAND-36 PFS). The orthopedic oncologists made their predictions based on case descriptions (including MRI scans) that reflected the preoperative status. The correlation between patient-reported and surgeon-predicted functional outcome was “very poor” to “poor” on both scores ( values ranged from 0.014 to 0.354). Patient-reported functional outcome was generally underestimated, by 8.7% on the TESS and 8.3% on the RAND-36 PFS. The most difficult and least difficult tasks on the RAND-36 PFS were also the most difficult and least difficult to predict, respectively. Most questions had a “poor” intersurgeon agreement. It was difficult to accurately predict the patient-reported functional outcome of LSS. Surgeons’ ability to predict functional scores can be improved the most by focusing on accurately predicting more demanding tasks. Sjoerd Kolk, Kevin Cox, Vivian Weerdesteyn, Gerjon Hannink, Jos Bramer, Sander Dijkstra, Paul Jutte, Joris Ploegmakers, Michiel van de Sande, Hendrik Schreuder, Nico Verdonschot, and Ingrid van der Geest Copyright © 2014 Sjoerd Kolk et al. All rights reserved. Preoperative Diagnosis of Usual Leiomyoma, Atypical Leiomyoma, and Leiomyosarcoma Tue, 21 Oct 2014 10:07:43 +0000 http://www.hindawi.com/journals/sarcoma/2014/498682/ Uterine smooth muscle tumors (SMTs) are common pelvic tumors in women, and most of them are diagnosed as usual leiomyoma (UL). Exclusion of malignant disease is important in the management of SMTs. However, differentiation of SMTs remains difficult. In this study, we aimed to improve the preoperative diagnosis of SMTs. We examined 21 ULs, 7 atypical leiomyomas (ALs), and 6 leiomyosarcomas (LMSs), all of which were diagnosed by uterine tumor biopsy. Immunohistochemical findings (low-molecular-mass polypeptide 2 (LMP2) and Ki-67) and clinical features (serum lactate dehydrogenase level and menopause) were evaluated. Statistically significant differences in the expression of LMP2 and Ki-67 were observed between UL and AL and between UL and LMS. The combined LMP2 and Ki-67 score was significantly different between UL and AL, between UL and LMS, and between AL and LMS. The combined immunohistochemistry and clinical findings score (total score) was also significantly different between pathological types. The findings of this study suggest that the accuracy of the preoperative diagnosis of SMTs may be improved by using a combination of immunohistochemical and clinical findings. M. Matsuda, T. Ichimura, M. Kasai, M. Murakami, N. Kawamura, T. Hayashi, and T. Sumi Copyright © 2014 M. Matsuda et al. All rights reserved. Clinical Features and Outcomes Differ between Skeletal and Extraskeletal Osteosarcoma Tue, 09 Sep 2014 08:16:03 +0000 http://www.hindawi.com/journals/sarcoma/2014/902620/ Background. Extraskeletal osteosarcoma (ESOS) is a rare subtype of osteosarcoma. We investigated patient characteristics, overall survival, and prognostic factors in ESOS. Methods. We identified cases of high-grade osteosarcoma with known tissue of origin in the Surveillance, Epidemiology, and End Results database from 1973 to 2009. Demographics were compared using univariate tests. Overall survival was compared with log-rank tests and multivariate analysis using Cox proportional hazards methods. Results. 256/4,173 (6%) patients with high-grade osteosarcoma had ESOS. Patients with ESOS were older, were more likely to have an axial tumor and regional lymph node involvement, and were female. Multivariate analysis showed ESOS to be favorable after controlling for stage, age, tumor site, gender, and year of diagnosis [hazard ratio 0.75 (95% CI 0.62 to 0.90); ]. There was an interaction between age and tissue of origin such that older patients with ESOS had superior outcomes compared to older patients with skeletal osteosarcoma. Adverse prognostic factors in ESOS included metastatic disease, larger tumor size, older age, and axial tumor site. Conclusion. Patients with ESOS have distinct clinical features but similar prognostic factors compared to skeletal osteosarcoma. Older patients with ESOS have superior outcomes compared to older patients with skeletal osteosarcoma. Sheila Thampi, Katherine K. Matthay, W. John Boscardin, Robert Goldsby, and Steven G. DuBois Copyright © 2014 Sheila Thampi et al. All rights reserved. Histopathological Diagnostic Discrepancies in Soft Tissue Tumours Referred to a Specialist Centre: Reassessment in the Era of Ancillary Molecular Diagnosis Tue, 05 Aug 2014 00:00:00 +0000 http://www.hindawi.com/journals/sarcoma/2014/686902/ Introduction. Soft tissue tumour pathology is a highly specialised area of surgical pathology, but soft tissue neoplasms can occur at virtually all sites and are therefore encountered by a wide population of surgical pathologists. Potential sarcomas require referral to specialist centres for review by pathologists who see a large number of soft tissue lesions and where appropriate ancillary investigations can be performed. We have previously assessed the types of diagnostic discrepancies between referring and final diagnosis for soft tissue lesions referred to our tertiary centre. We now reaudit this 6 years later, assessing changes in discrepancy patterns, particularly in relation to the now widespread use of ancillary molecular diagnostic techniques which were not prevalent in our original study. Materials and Methods. We compared the sarcoma unit's histopathology reports with referring reports on 348 specimens from 286 patients with suspected or proven soft tissue tumours in a one-year period. Results. Diagnostic agreement was seen in 250 cases (71.8%), with 57 (16.4%) major and 41 (11.8%) minor discrepancies. There were 23 cases of benign/malignant discrepancies (23.5% of all discrepancies). 50 ancillary molecular tests were performed, 33 for aiding diagnosis and 17 mutational analyses for gastrointestinal stromal tumour to guide therapy. Findings from ancillary techniques contributed to 3 major and 4 minor discrepancies. While the results were broadly similar to those of the previous study, there was an increase in frequency of major discrepancies. Conclusion. Six years following our previous study and notably now in an era of widespread ancillary molecular diagnosis, the overall discrepancy rate between referral and tertiary centre diagnosis remains similar, but there is an increase in frequency of major discrepancies likely to alter patient management. A possible reason for the increase in major discrepancies is the increasing lack of exposure to soft tissue cases in nonspecialist centres in a time of subspecialisation. The findings support the national guidelines in which all suspected soft tissue tumour pathology specimens should be referred to a specialist sarcoma unit. Khin Thway, Jayson Wang, Taka Mubako, and Cyril Fisher Copyright © 2014 Khin Thway et al. All rights reserved. Computer-Assisted Planning and Patient-Specific Instruments for Bone Tumor Resection within the Pelvis: A Series of 11 Patients Wed, 02 Jul 2014 11:31:20 +0000 http://www.hindawi.com/journals/sarcoma/2014/842709/ Pelvic bone tumor resection is challenging due to complex geometry, limited visibility, and restricted workspace. Accurate resection including a safe margin is required to decrease the risk of local recurrence. This clinical study reports 11 cases of pelvic bone tumor resected by using patient-specific instruments. Magnetic resonance imaging was used to delineate the tumor and computerized tomography to localize it in 3D. Resection planning consisted in desired cutting planes around the tumor including a safe margin. The instruments were designed to fit into unique position on the bony structure and to indicate the desired resection planes. Intraoperatively, instruments were positioned freehand by the surgeon and bone cutting was performed with an oscillating saw. Histopathological analysis of resected specimens showed tumor-free bone resection margins for all cases. Available postoperative computed tomography was registered to preoperative computed tomography to measure location accuracy (minimal distance between an achieved and desired cut planes) and errors on safe margin (minimal distance between the achieved cut planes and the tumor boundary). The location accuracy averaged 2.5 mm. Errors in safe margin averaged −0.8 mm. Instruments described in this study may improve bone tumor surgery within the pelvis by providing good cutting accuracy and clinically acceptable margins. François Gouin, Laurent Paul, Guillaume Anthony Odri, and Olivier Cartiaux Copyright © 2014 François Gouin et al. All rights reserved. Cell Senescence in Myxoid/Round Cell Liposarcoma Tue, 24 Jun 2014 06:54:41 +0000 http://www.hindawi.com/journals/sarcoma/2014/208786/ Myxoid/round cell liposarcoma (MLS/RCLS) is the second most common liposarcoma type and characterized by the fusion oncogenes FUS-DDIT3 or EWSR1-DDIT3. Previous analysis of cell cycle regulatory proteins revealed a prominent expression of G1-cyclins, cyclin dependent kinases, and their inhibitors but very few cells progressing through the G1/S boundary. Here, we extend the investigation to proteins involved in cell senescence in an immunohistochemistry based study of 17 MLS/RCLS cases. Large subpopulations of tumor cells expressed the RBL2 pocket protein and senescence associated heterochromatin 1γ and IL8 receptor β. We conclude that MLS/RCLS tissues contain major populations of senescent tumor cells and this may explain the slow growth rate of this tumor type. Christina Kåbjörn Gustafsson, Anders Ståhlberg, Katarina Engtröm, Anna Danielsson, Ingela Turesson, and Pierre Åman Copyright © 2014 Christina Kåbjörn Gustafsson et al. All rights reserved. Adult versus Pediatric Neuroblastoma: The M.D. Anderson Cancer Center Experience Thu, 12 Jun 2014 07:41:08 +0000 http://www.hindawi.com/journals/sarcoma/2014/375151/ Background. Staging and treatment of adult neuroblastoma has yet to be formalized. We sought to determine the utility of the pediatric classification system in adults and determine the efficacy of different treatment modalities. Methods. Medical records of 118 adults (patients >17 years old) and 112 pediatric patients (ages 2–17), who were treated for neuroblastoma at M.D. Anderson Cancer Center from January 1994 to September 2012, were reviewed. International neuroblastoma risk group (INRG) variables were abstracted. The primary outcome of interest was actuarial progression-free survival. Results. Median age of pediatric patients was 5 years (range 3–16) and 47 years (range 18–82) for adult patients. There were no differences in PFS or OS between stage-matched risk categories between pediatric and adult patients (L1-, L2-, and M-). In the treatment of L1 disease, median PFS for adults treated with surgery and radiation was 11.1 months compared with single modality local treatment ± chemotherapy (6.4 and 5.1 months, resp.; ). Median PFS in L2 adult patients was 5.2 months with local therapy and 4 months with the addition of chemotherapy (). Conclusions. Adult and pediatric patients with neuroblastoma achieve similar survival outcomes. INRG classification should be employed to stratify adult neuroblastoma patients and help select treatment. Henry J. Conter, Vancheswaran Gopalakrishnan, Vinod Ravi, Joann L. Ater, Shreyaskumar Patel, and Dejka M. Araujo Copyright © 2014 Henry J. Conter et al. All rights reserved. Cost-Effectiveness of Pazopanib in Advanced Soft Tissue Sarcoma in the United Kingdom Thu, 12 Jun 2014 07:32:45 +0000 http://www.hindawi.com/journals/sarcoma/2014/481071/ In the phase III PALETTE trial, pazopanib improved progression-free survival (PFS) compared with placebo in patients with advanced/metastatic soft tissue sarcomas (mSTS) who had received prior chemotherapy. We used a multistate model to estimate expected PFS, overall survival (OS), lifetime STS treatment costs, and quality-adjusted life-years (QALYs) for patients receiving pazopanib, placebo, trabectedin, ifosfamide, or gemcitabine plus docetaxel as second-line mSTS therapies. The cost-effectiveness of pazopanib was expressed as the incremental costs per QALY gained. Estimates of PFS/OS, adverse events, and utilities for pazopanib and placebo were from the PALETTE trial. Estimates of relative effectiveness of the other comparators were from an unadjusted indirect comparison versus pazopanib. Costs were from published sources. Pazopanib is estimated to increase QALYs by 0.128 and costs by £7,976 versus placebo; cost per QALY gained with pazopanib versus placebo is estimated to be £62,000. Compared with the other chemotherapies, pazopanib provides similar QALYs at a lower cost. Pazopanib may not be cost-effective versus placebo but may be cost-effective versus the most commonly used active treatments, although this conclusion is uncertain. Given the unmet need for effective treatments for mSTS, pazopanib may be an appropriate alternative to some currently used medications in the United Kingdom. Jordan Amdahl, Stephanie C. Manson, Robert Isbell, Ayman Chit, Jose Diaz, Lily Lewis, and Thomas E. Delea Copyright © 2014 Jordan Amdahl et al. All rights reserved.