Sarcoma https://www.hindawi.com The latest articles from Hindawi © 2017 , Hindawi Limited . All rights reserved. Ovary-Sparing Radiation Planning Techniques Can Achieve Ovarian Dose Reduction for Soft Tissue Sarcoma of the Buttock and Thigh Mon, 18 Sep 2017 00:00:00 +0000 http://www.hindawi.com/journals/sarcoma/2017/2796925/ Background and Objectives. Attention to ovary dose is important for premenopausal women undergoing radiation therapy (RT) and must not be overlooked when treating extremity sarcoma. We assessed whether ovary-sparing RT plans could decrease ovary dose without compromising target coverage. Methods. Standard sarcoma target volumes and organs at risk (OAR) were contoured by a sarcoma dedicated radiation oncologist on CT planning scans for 23 women with thigh or buttock sarcoma. IMRT plans (50 Gy) with and without attempted ovary-sparing were created by an expert sarcoma dosimetrist. Results. All plans met target coverage goals. Compared to standard plans, ovary-sparing plans had lower mean bilateral ovary doses (MBOD) (652 versus 483 cGy, ) but higher bone doses (mean V50: 8.5% versus 6.9%, ) and lower conformity indexes (1.12 versus 1.19, ). Tumors < 8 cm from the pubic symphysis had significant MBOD reduction with ovary-sparing plans (376 cGy versus 619 cGy, ). On multivariate analysis, distance to pubic symphysis and proximal medial thigh site were associated with MBOD reduction with ovary-sparing plan. Conclusions. For preoperative IMRT, ovary-sparing planning significantly reduces ovarian dose in women with sarcoma of the proximal thigh and near the pubic symphysis. Konstantin A. Kovtun, Wee-Pin Yeo, Catherine H. Phillips, Akila Viswanathan, and Elizabeth H. Baldini Copyright © 2017 Konstantin A. Kovtun et al. All rights reserved. SARC006: Phase II Trial of Chemotherapy in Sporadic and Neurofibromatosis Type 1 Associated Chemotherapy-Naive Malignant Peripheral Nerve Sheath Tumors Tue, 12 Sep 2017 07:43:06 +0000 http://www.hindawi.com/journals/sarcoma/2017/8685638/ Background. Worse chemotherapy response for neurofibromatosis type 1- (NF1-) associated compared to sporadic malignant peripheral nerve sheath tumors (MPNST) has been reported. Methods. We evaluated the objective response (OR) rate of patients with AJCC Stage III/IV chemotherapy-naive NF1 MPNST versus sporadic MPNST after 4 cycles of neoadjuvant chemotherapy, 2 cycles of ifosfamide/doxorubicin, and 2 cycles of ifosfamide/etoposide. A Simon optimal two-stage design was used (target response rate 40%). Results. 34 NF1 (median age 33 years) and 14 sporadic (median age 40 years) MPNST patients enrolled. Five of 28 (17.9%) evaluable NF1 MPNST patients had a partial response (PR), as did 4 of 9 (44.4%) patients with sporadic MPNST. Stable disease (SD) was achieved in 22 NF1 and 4 sporadic MPNST patients. In both strata, results in the initial stages met criteria for expansion of enrollment. Only 1 additional PR was observed in the expanded NF1 stratum. Enrollment was slower than expected and the trial closed before full accrual. Conclusions. This trial was not powered to detect differences in response rates between NF1 and sporadic MPNST. While the OR rate was lower in NF1 compared to sporadic MPNST, qualitative responses were similar, and disease stabilization was achieved in most patients. Christine S. Higham, Seth M. Steinberg, Eva Dombi, Arie Perry, Lee J. Helman, Scott M. Schuetze, Joseph A. Ludwig, Arthur Staddon, Mohammed M. Milhem, Daniel Rushing, Robin L. Jones, Michael Livingston, Stewart Goldman, Christopher Moertel, Lars Wagner, David Janhofer, Christina M. Annunziata, Denise Reinke, Lauren Long, David Viskochil, Larry Baker, and Brigitte C. Widemann Copyright © 2017 Christine S. Higham et al. All rights reserved. High-Dose Ifosfamide Chemotherapy in a Series of Patients Affected by Myxoid Liposarcoma Wed, 30 Aug 2017 07:38:26 +0000 http://www.hindawi.com/journals/sarcoma/2017/3739159/ Background. To report on the activity of high-dose prolonged-infusion ifosfamide (HDIFX) chemotherapy in a retrospective series of patients affected by myxoid liposarcoma treated at Fondazione IRCCS Istituto Nazionale dei Tumori in Milan, Italy. Patients and Methods. Patients with an advanced myxoid liposarcoma treated with HDIFX (14 g/sqm, i.v., prolonged infusion of 14 days every 28 days) as a single agent between May 2002 and April 2017 were retrospectively reviewed. All pathologic diagnoses were centrally reviewed and molecularly confirmed. Response was evaluated by RECIST, and survival functions were computed by the Kaplan-Meier method. Results. Eleven patients with advanced myxoid liposarcoma were treated with HDIFX (male/female = 9/2, median age 33 years, range 31–75). Among these, 1/11 received HDIFX in first line, 5/11 in second line, 3/11 in third line, and 2/11 in fourth line for a median course number of 3 (range 2–7). No RECIST objective responses were observed. Overall median progression-free survival was 1,9 months. Median overall survival was 37 months. At a median follow-up of 115 months, 1 patient is alive. Conclusions. In this series of patients affected by advanced myxoid liposarcoma, chemotherapy with HDIFX was essentially inactive. Vittoria Colia, Elena Fumagalli, Salvatore Provenzano, Rossella Bertulli, Silvia Stacchiotti, Carlo Morosi, Paola Collini, Alessandro Gronchi, Paolo G. Casali, and Roberta Sanfilippo Copyright © 2017 Vittoria Colia et al. All rights reserved. Multimodal Approach of Pulmonary Artery Intimal Sarcoma: A Single-Institution Experience Sun, 20 Aug 2017 09:57:25 +0000 http://www.hindawi.com/journals/sarcoma/2017/7941432/ Introduction. Pulmonary artery sarcoma (PAS) is a rare tumor, whose therapeutic approach is mainly based on surgery, either pneumonectomy or pulmonary endarterectomy (PEA). The prognosis reported in published series is very poor, with survival of 1.5 months without any kind of treatment. Patients and Methods. From January 2010 to January 2016, 1027 patients were referred to our hospital for symptoms of acute or chronic pulmonary thromboembolic disease. Twelve patients having a confirmed diagnosis of PAS underwent PEA. Median age was 64.5 years. Most patients had a long history of symptoms, having a median time of 7.5 months from onset of symptoms to surgery. Results. Following PEA and cardiopulmonary rehabilitation, 10 patients received conventional chemotherapy with doxorubicin and ifosfamide, starting at a median of 42 days from surgery. Four patients also received radiotherapy. Four patients have died due to disease progression, while 7 are still alive, with 5 being disease-free at 4–55+ months from diagnosis. Conclusions. In patients with PAS, a multimodal approach including PEA, CT, and RT is feasible but it should be evaluated individually, according to the tumor extension and the patient’s clinical condition. Apart from improving quality of life mainly by reducing or delaying symptoms due to PH, it may improve life expectancy. S. Secondino, V. Grazioli, F. Valentino, M. Pin, A. Pagani, A. Sciortino, C. Klersy, M. G. Callegari, P. Morbini, R. Dore, M. Paulli, P. Pedrazzoli, and A. M. D’armini Copyright © 2017 S. Secondino et al. All rights reserved. Preoperative Factors Associated with Infiltrative Histologic Growth Patterns in Extremity Soft Tissue Sarcoma Thu, 20 Jul 2017 00:00:00 +0000 http://www.hindawi.com/journals/sarcoma/2017/5419394/ Soft tissue sarcoma (STS) with an infiltrative histologic growth pattern, when compared to STS with an expansile pattern, may pose difficulties in local control. Preoperative assessment of the presence of infiltrative histologic growth pattern would be helpful in deciding treatment strategies. A review of 144 patients who underwent surgery for extremity STS was performed. Microscopically, the histologic growth pattern was defined as infiltrative if the penetration of the tumor cells into the surrounding tissue was observed. Possible clinicopathologic factors that might be associated with infiltrative histologic growth pattern were investigated with regard to patient demographics, tumor characteristics, and MRI findings. Of the 144 tumors, 71 (49%) showed infiltrative histologic growth pattern. On multivariate analysis, histological subtypes other than liposarcoma (OR = 4.57, ) and infiltrative border on MRI (OR = 2.48, ) were independent factors associated with infiltrative histologic growth pattern. Predictive index based on these two factors showed a significant improved accuracy (ROC-AUC = 0.647) for predicting infiltrative histologic growth pattern compared to either factor alone. Our data suggests that liposarcoma histology and tumor border on MRI can predict histologic growth pattern in extremity STS. Jong Woong Park, Han-Soo Kim, Cheol Lee, Hye Jin Yoo, Ji Yeon Yun, and Ilkyu Han Copyright © 2017 Jong Woong Park et al. All rights reserved. Cross-Cultural Adaptation, Translation, and Validation of the Toronto Extremity Salvage Score for Extremity Bone and Soft Tissue Tumor Patients in Netherlands Thu, 20 Jul 2017 00:00:00 +0000 http://www.hindawi.com/journals/sarcoma/2017/6197525/ Purpose. The aim of this study was to translate and culturally adapt the Toronto Extremity Salvage Score (TESS) to Dutch and to validate the translated version. Methods. The TESS lower and upper extremity versions (LE and UE) were translated to Dutch according to international guidelines. The translated version was validated in 98 patients with surgically treated bone or soft tissue tumors of the LE or UE. To assess test-retest reliability, participants were asked to fill in a second questionnaire after one week. Construct validity was determined by computing Spearman rank correlations with the Short Form- (SF-) 36. Results. The internal consistency (0.957 and 0.938 for LE and UE, resp.) and test-retest reliability (intraclass correlation coefficients 0.963 and 0.969 for LE and UE, resp.) were good for both questionnaires. The Dutch LE and UE TESS versions correlated most strongly with the SF-36 physical function dimension ( for LE, 0.726 for UE) and the physical component summary score ( and 0.797 for LE and UE). Interpretation. The Dutch TESS questionnaire for lower and upper extremities is a consistent, reliable, and valid instrument to measure patient-reported physical function in surgically treated patients with a soft tissue or bone tumor. Julie J. Willeumier, C. W. P. G. van der Wal, Robert J. P. van der Wal, P. D. S. Dijkstra, Thea P. M. Vliet Vlieland, and Michiel A. J. van de Sande Copyright © 2017 Julie J. Willeumier et al. All rights reserved. Concurrent Imatinib and Radiation Therapy for Unresectable and Symptomatic Desmoid Tumors Wed, 05 Jul 2017 00:00:00 +0000 http://www.hindawi.com/journals/sarcoma/2017/2316839/ Desmoid tumors are locally aggressive fibroproliferative neoplasms that can lead to pain and dysfunction due to compression of nerves and surrounding structures. Desmoid tumors often progress through medical therapy, and there is frequently a delay of multiple months before radiation can provide symptomatic relief. To achieve more rapid symptomatic relief and tumor regression for unresectable desmoid tumors causing significant morbidity such as brachial plexus impingement with loss of extremity function, we have selectively utilized a combination of imatinib and radiation therapy. Here, we retrospectively review four patients treated with concurrent imatinib and radiation therapy. The treatment was typically tolerated with minimal toxicity though one patient developed avascular necrosis of the irradiated humeral head possibly related to the combined treatment. All the patients treated have had a partial response or stable disease on imaging. Improvement of symptoms was observed in all the treated patients with a median time to relief of 2.5 months after starting radiation therapy. Concurrent radiation and imatinib may represent a viable treatment option for unresectable and symptomatic desmoid tumors where rapid relief is needed to prevent permanent loss of function. Everett J. Moding, Lynn Million, Raffi Avedian, Pejman Ghanouni, Christian Kunder, and Kristen N. Ganjoo Copyright © 2017 Everett J. Moding et al. All rights reserved. Predictors of Wound Complications following Radiation and Surgical Resection of Soft Tissue Sarcomas Thu, 15 Jun 2017 06:44:05 +0000 http://www.hindawi.com/journals/sarcoma/2017/5465130/ Wound complications represent a major source of morbidity in patients undergoing radiation therapy (RT) and surgical resection of soft tissue sarcomas (STS). We investigated whether factors related to RT, surgery, patient comorbidities, and tumor histopathology predict the development of wound complications. An observational study of patients who underwent STS resection and RT was performed. The primary outcome was the occurrence of any wound complication up to four months postoperatively. Significant predictors of wound complications were identified using multivariable logistic regression. Sixty-five patients representing 67 cases of STS were identified. Median age was 59 years (range 22–90) and 34 (52%) patients were female. The rates of major wound complications and any wound complications were 21% and 33%, respectively. After adjusting for radiation timing, diabetes (OR 9.6; 95% CI 1.4–64.8; ), grade ≥2 radiation dermatitis (OR 4.8; 95% CI 1.2–19.2; ), and the use of 3D conformal RT (OR 4.6; 95% CI 1.1–20.0; ) were associated with an increased risk of any wound complication on multivariable analysis. These data suggest that radiation dermatitis and radiation modality are predictors of wound complications in patients with STS. Drake G. LeBrun, David M. Guttmann, Jacob E. Shabason, William P. Levin, Stephen J. Kovach, and Kristy L. Weber Copyright © 2017 Drake G. LeBrun et al. All rights reserved. Synovial Sarcoma of the Head and Neck: A Single Institution Review Mon, 05 Jun 2017 07:00:09 +0000 http://www.hindawi.com/journals/sarcoma/2017/2016752/ Background. The prognosis and clinical characteristics of head and neck synovial sarcomas (HNSS) are unclear. Herein, we present an update using a cohort of patients treated at our institution. Methods. We performed a retrospective chart review of 44 patients diagnosed with primary HNSS between March 1990 and June 2012. Overall survival (OS) and progression-free survival (PFS) curves were estimated and hazard ratios (HRs) were calculated. Results. The entire cohort’s median PFS was 4.6 years, and 20 of the 44 (45%) patients developed either local or distant recurrence. Tumor size ≥ 5 cm (, HR = 4.69; 95% CI = 1.34–16.38) and a primary presentation in the soft tissues of the neck (, HR = 2.41; 95% CI = 1.003–5.82) were associated with significantly worse PFS. The OS and PFS of patients who received definitive local therapy versus those who received additional adjuvant systemic therapy did not differ significantly. Conclusion. Despite the treatment challenges associated with HNSS, our cohort of patients had a better prognosis than one might expect in this unfavorable anatomical location. Our findings suggest that tumor size and site are predictive of PFS and that wide surgical excision is of vital importance, since traditional cytotoxic chemotherapy has limited efficacy at this site. Vancheswaran Gopalakrishnan, Behrang Amini, Michael J. Wagner, Erica N. Nowell, Alexander J. Lazar, Patrick P. Lin, Robert S. Benjamin, and Dejka M. Araujo Copyright © 2017 Vancheswaran Gopalakrishnan et al. All rights reserved. Pasteurized Autograft-Prosthesis Composite Reconstruction May Not Be a Viable Primary Procedure for Large Skeletal Defects after Resection of Sarcoma Sun, 04 Jun 2017 08:22:21 +0000 http://www.hindawi.com/journals/sarcoma/2017/9710964/ Background. Among various types of composite biological reconstruction, pasteurized autograft-prosthesis composite (PPC) is popular when allograft is unavailable. Previous limited cohort study indicated result comparable to tumor prosthesis. However, as case number and follow-up increase, we experienced more complications than anticipated. We questioned the usefulness of PPC as a viable reconstructive option. Methods. We reviewed 142 PPCs and analyzed overall and location-related survival and factors associated with the failure of PPC. Results. Twenty-year survival rate of 142 PPCs was 39.8 ± 10.0%. Fifty-two (36.6%) of 142 PPCs showed failure. Among various locations, the proximal femur showed best survival: 78.0 ± 9.9%. Final status of the 52 failed PPCs was modular tumor prosthesis in 23 (43%), arthrodesis in 11 (21%), pseudarthrosis in 7 (13%), amputation in 7 (13%), and allograft-prosthesis composite in 4 (8%). Tumor volume > 200 cc , pasteurization length ≤ 10 cm , male sex , and locations in pelvis or tibia were poor prognostic factors. Conclusions. Long-term survival of PPCs was below expectations. Despite the complexity of the procedure, there is little survival gain over tumor prosthesis. PPC may be indicated when a modular prosthesis is not readily available. Seung Yong Lee, Dae-Geun Jeon, Wan Hyeong Cho, Won Seok Song, Chang-Bae Kong, and Bum Suk Kim Copyright © 2017 Seung Yong Lee et al. All rights reserved. Malignant Peripheral Nerve Sheath Tumors State of the Science: Leveraging Clinical and Biological Insights into Effective Therapies Tue, 16 May 2017 00:00:00 +0000 http://www.hindawi.com/journals/sarcoma/2017/7429697/ Malignant peripheral nerve sheath tumor (MPNST) is the leading cause of mortality in patients with neurofibromatosis type 1. In 2002, an MPNST consensus statement reviewed the current knowledge and provided guidance for the diagnosis and management of MPNST. Although the improvement in clinical outcome has not changed, substantial progress has been made in understanding the natural history and biology of MPNST through imaging and genomic advances since 2002. Genetically engineered mouse models that develop MPNST spontaneously have greatly facilitated preclinical evaluation of novel drugs for translation into clinical trials led by consortia efforts. Continued work in identifying alterations that contribute to the transformation, progression, and metastasis of MPNST coupled with longitudinal follow-up, biobanking, and data sharing is needed to develop prognostic biomarkers and effective prevention and therapeutic strategies for MPNST. AeRang Kim, Douglas R. Stewart, Karlyne M. Reilly, David Viskochil, Markku M. Miettinen, and Brigitte C. Widemann Copyright © 2017 AeRang Kim et al. All rights reserved. Results of a Qualitative Study to Develop a Patient Reported Outcome Measure for Patients with 4 Subtypes of Soft Tissue Sarcoma Sun, 14 May 2017 08:45:57 +0000 http://www.hindawi.com/journals/sarcoma/2017/6868030/ Objective. The objective of this research was to develop a disease-specific symptom inventory for soft tissue sarcoma. Methods. Literature review and clinical expert and patient interviews were conducted to determine disease-specific symptoms important to patients with one of the four STS subtypes. Clinical experts identified the most relevant STS symptom items from the item pool developed from literature review. Concept elicitation interviews were conducted with patients to elicit their STS symptom experiences followed by a completion of the draft symptom list via web survey. A cognitive interview was conducted on the comprehension and importance of the symptom items. Results. Eighty-three symptom items were compiled and discussed with three clinical experts who identified 26 symptoms specific to the four STS subtypes. A total sample of 27 STS participants with self-reported leiomyosarcoma (74%), undifferentiated sarcoma (15%), synovial sarcoma (7%), or liposarcoma (4%) diagnosis completed the web survey and 10 were interviewed. The draft 12-item STS-specific symptom inventory includes abdominal pain, pressure in abdomen, early satiety, bloating, gastrointestinal pain, muscle pain, bone pain, heavy menstrual flow, shortness of breath, chest pain, cough, and painful menstruation. Conclusion. A number of symptoms are common across STS subtypes and may form a single STS symptom inventory. Anne M. Skalicky, Sameer R. Ghate, Jose Ricardo Perez, and Anne M. Rentz Copyright © 2017 Anne M. Skalicky et al. All rights reserved. Neoadjuvant Ifosfamide and Epirubicin in the Treatment of Malignant Peripheral Nerve Sheath Tumors Thu, 04 May 2017 08:30:24 +0000 http://www.hindawi.com/journals/sarcoma/2017/3761292/ Background and Objectives. Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft tissue sarcomas with poor overall survival. Response to chemotherapy has been debated for these tumors. Methods. We performed a retrospective analysis of the patients at our institution with a biopsy-proven diagnosis of MPNST that underwent neoadjuvant chemotherapy prior to surgery. Results. We retrospectively identified five patients who received neoadjuvant chemotherapy with epirubicin and ifosfamide that demonstrated a 30% reduction in tumor growth and a 60% response rate by RECIST criteria. Additionally, a metabolic response was observed in all three patients who received serial PET scans during neoadjuvant treatment. The clinical benefit rate, which includes stable disease, was 100%. Conclusions. Our data suggest that MPNSTs do respond to epirubicin and ifosfamide based chemotherapy and prospective studies are warranted to further define the clinical benefit. Angela C. Hirbe, Pippa F. Cosper, Sonika Dahiya, and Brian A. Van Tine Copyright © 2017 Angela C. Hirbe et al. All rights reserved. Evaluation of Quality of Life at Progression in Patients with Soft Tissue Sarcoma Sun, 23 Apr 2017 00:00:00 +0000 http://www.hindawi.com/journals/sarcoma/2017/2372135/ Introduction. Soft Tissue Sarcoma (STS) is a rare malignancy of mesodermal tissue, with international incidence estimates between 1.8 and 5 per 100,000 per year. Understanding quality of life (QoL) and the detrimental impact of disease progression is critical for long-term care and survival. Objectives. The primary objective was to explore the relationship between disease progression and health-related quality of life (HRQoL) using data from Eisai’s study (E7389-G000-309). Methods. This was a 1 : 1 randomized, open-label, multicenter, Phase 3 study comparing the efficacy and safety of eribulin versus dacarbazine in patients with advanced STS. The QoL analysis was conducted for the baseline and progression populations using the European Organization for Research and Treatment of Cancer 30-item core QoL questionnaire (EORTC QLQ-C30). Results. There were no statistical differences between the two treatment arms at baseline for any domain (; ). Of the 399 patients who experienced disease progression (unadjusted and adjusting for histology), dacarbazine patients had significantly lower Global Health Status, Physical Functioning scores, and significantly worse Nausea and Vomiting, Insomnia, and Appetite Loss (). Conclusions. These results indicate differences in HRQoL overall and at progression between dacarbazine and eribulin patients, with increases in symptom severity observed among dacarbazine patients. Stacie Hudgens, Anna Forsythe, Ilias Kontoudis, David D’Adamo, Ashley Bird, and Hans Gelderblom Copyright © 2017 Stacie Hudgens et al. All rights reserved. Variations of Surveillance Practice for Patients with Bone Sarcoma: A Survey of Australian Sarcoma Clinicians Tue, 28 Feb 2017 09:34:06 +0000 http://www.hindawi.com/journals/sarcoma/2017/1837475/ Introduction. After treatment, bone sarcoma patients carry a high chance of relapse and late effects from multimodal therapy. We hypothesize that significant variation in surveillance practice exists between pediatric medical oncology (PO) and nonpediatric medical oncology (NP) sarcoma disciplines. Methods. Australian sarcoma clinicians were approached to do a web based survey that assessed radiologic surveillance (RS) strategies, late toxicity assessment, and posttreatment psychosocial interventions. Results. In total, 51 clinicians responded. No differences were identified in local disease RS. In metastatic disease response assessment, 100% of POs (23/23) and 93% of NPs (24/26) conducted CT chest. However, this was more likely to occur for NPs in the context of a CT chest/abdomen/pelvis (NP: 10/26; PO: 1/23; ). POs were more likely to use CXR for RS (). POs showed more prescriptive intensity in assessment of heart function (), hearing (), and fertility (). POs were more likely to deliver written information for health maintenance/treatment summary (). The majority of respondents described enquiring about psychosocial aspects of health (/37, 89%), but a routine formal psychosocial screen was only used by 23% (/26). Conclusion. There is high variability in bone sarcoma surveillance between PO and NP clinicians. Efforts to harmonize approaches would allow early and late effects recognition/intervention and facilitate improved patient care/transition and research. Jeremy Lewin, Kate Thompson, Susie Bae, Jayesh Desai, Robyn Strong, Denise Caruso, Deborah Howell, Alan Herschtal, Michael Sullivan, and Lisa Orme Copyright © 2017 Jeremy Lewin et al. All rights reserved. Correlation of Ezrin Expression Pattern and Clinical Outcomes in Ewing Sarcoma Thu, 26 Jan 2017 00:00:00 +0000 http://www.hindawi.com/journals/sarcoma/2017/8758623/ Background. Ezrin is a membrane-cytoskeleton linker protein that has been associated with metastasis and poor outcomes in osteosarcoma and high-grade soft tissue sarcomas. The prognostic value of ezrin expression in Ewing sarcoma is unknown. Methods. The relationship between ezrin expression and outcome was analyzed in a cohort of 53 newly diagnosed Ewing sarcoma patients treated between 2000 and 2011. The intensity and proportion of cells with ezrin immunoreactivity were assessed in diagnostic tumor tissue using a semiquantitative scoring system to yield intensity and positivity scores for each tumor. Results. Ezrin expression was detected in 72% (38/53) of tumor samples. The proportion of patients with metastatic disease was equal in the positive and negative ezrin expression groups. There was no significant difference in the 5-year event-free survival (EFS) between patients with positive versus negative ezrin expression. Patients whose tumor sample showed high ezrin intensity had significantly better 5-year EFS when compared to patients with low/no ezrin intensity (78% versus 55%; ). Conclusions. Ezrin expression can be detected in the majority of Ewing sarcoma tumor samples. Intense ezrin expression may be correlated with a favorable outcome; however further investigation with a larger cohort is needed to validate this finding. Thomas Cash, Hong Yin, Courtney McCracken, Zhi Geng, Steven G. DuBois, Bahig M. Shehata, Thomas A. Olson, Howard M. Katzenstein, and Cynthia Wetmore Copyright © 2017 Thomas Cash et al. All rights reserved. Routes to Diagnosis for Suspected Sarcoma: The Impact of Symptoms and Clinical Findings on the Diagnostic Process Mon, 26 Dec 2016 12:04:11 +0000 http://www.hindawi.com/journals/sarcoma/2016/8639272/ Background and Objectives. Sarcoma patients often experience delay before diagnosis. We examined the association between presenting symptoms/signs and time intervals for suspected sarcoma patients. Methods. 545 consecutive patients suspected for sarcoma referred over a one-year period were included. Median time intervals in routes to diagnosis were collected from medical records and questionnaires. Results. 102 patients (18.7%) had a sarcoma; 68 (12.5%) had other malignancies. Median interval for the patient (time from first symptom to first doctor visit), primary care, local hospital, sarcoma center, diagnostic, and total interval for sarcoma patients were 77, 17, 29, 17, 65, and 176 days, respectively. Sarcoma patients visited more hospital departments and had longer median primary care (+10 days) and diagnostic intervals (+19 days) than patients with benign conditions. Median primary care (−19 days) and sarcoma center (−4 days) intervals were shorter for patients with a lump versus no lump. Median patient (+40 days), primary care (+12 days), diagnostic (+17 days), and total intervals (+78 days) were longer for patients presenting with pain versus no pain. GP suspicion of malignancy shortened local hospital (−20 days) and total intervals (−104 days). Conclusions. The main part of delay could be attributed to the patient and local hospitals. Length of time intervals was associated with presenting symptoms/signs and GP suspicion. Heidi Buvarp Dyrop, Peter Vedsted, Mathias Rædkjær, Akmal Safwat, and Johnny Keller Copyright © 2016 Heidi Buvarp Dyrop et al. All rights reserved. Cryosurgery as Additional Treatment in Tenosynovial Giant Cell Tumors Mon, 26 Dec 2016 08:39:21 +0000 http://www.hindawi.com/journals/sarcoma/2016/3072135/ Introduction. Tenosynovial giant cell tumors (TGCT) emerge from the synovium and can behave aggressively. Surgical resection is the standard treatment. However, up to half of the patients with diffuse type show recurrences. Several additional treatments have been applied to reduce recurrences; none of these treatments was proven to be superior to surgical resection solely. This article describes the results of additional cryosurgery to surgical resection. Materials and Methods. We retrospectively evaluated 141 TGCT patients, between 1999 and 2007. Twelve patients had additional cryosurgery. The knee (), hip (), ankle (), and elbow () were affected. Primary outcome variables were treatment indications, recurrences, and complications. Results. Indications for additional cryosurgery were extended disease, bone involvement, and locations that are difficult to surgically get disease-free such as cruciate ligaments. Five patients had recurrent disease, all of which had prior treatments. None of the primary treated patients had recurrent disease. One patient had a deep infection. Discussion. Cryosurgery may serve as an additional treatment for diffuse TCGT in selected cases. However, because of the small number of patients and the heterogeneous group we could not prove an advantage of additional cryosurgery over surgical resection only. Cryosurgery should be considered for further evaluation in a prospective study. If there is any effect it would be helpful, especially in patients with multiple TGCT recurrences. F. G. M. Verspoor, A. Scholte, I. C. M. van der Geest, G. Hannink, and H. W. B. Schreuder Copyright © 2016 F. G. M. Verspoor et al. All rights reserved. Giant Cell Tumor: A Rare Condition in the Immature Skeleton—A Retrospective Study of Symptoms, Treatment, and Outcome in 16 Children Wed, 23 Nov 2016 05:56:27 +0000 http://www.hindawi.com/journals/sarcoma/2016/3079835/ Background. Pediatric giant cell tumor (GCT) of bone is rare and the course of the disease in the immature skeleton is sparsely described. We performed a retrospective study addressing symptoms, treatment, and outcome in children with GCT. Methods. Review of medical records and images of patients with GCT. Patients were detected from our hospital prospective database and those with open epiphyseal cartilages were included. Results. 16 children (75% girls) from 6 to 15 years old were identified. Eight lesions (50%) were in long bones and 4 (25%) in flat bones. One lesion appeared to be purely epiphyseal. All patients had pain as the initial symptom. Local recurrence developed in 2 patients. 14 of 16 patients returned to normal activity with no sequelae. One patient developed anisomelia after surgery. Conclusions. The biological tumor behavior in children does not seem to differ from what is reported in adults. Lesions in flat bones are very unusual, but our data alone do not provide enough evidence to conclude that this is more common in the immature skeleton. Literature review showed only one previous case report describing a purely epiphyseal GCT. Intralesional curettage is appropriate treatment and gives good functional results with acceptable recurrence rates. Thale M. Asp Strøm, Anette Torød Skeie, Ingvild Koren Lobmaier, and Olga Zaikova Copyright © 2016 Thale M. Asp Strøm et al. All rights reserved. miR-125b and miR-100 Are Predictive Biomarkers of Response to Induction Chemotherapy in Osteosarcoma Mon, 21 Nov 2016 08:11:03 +0000 http://www.hindawi.com/journals/sarcoma/2016/1390571/ Osteosarcoma is the most common primary malignancy in bone. Patients who respond poorly to induction chemotherapy are at higher risk of adverse prognosis. The molecular basis for such poor prognosis remains unclear. We investigated miRNA expression in eight open biopsy samples to identify miRNAs predictive of response to induction chemotherapy and thus maybe used for risk stratification therapy. The samples were obtained from four patients with inferior necrosis (Huvos I/II) and four patients with superior necrosis (Huvos III/IV) following induction chemotherapy. We found six miRNAs, including miR-125b and miR-100, that were differentially expressed > 2-fold () in patients who respond poorly to treatment. The association between poor prognosis and the abundance of miR-125b and miR-100 was confirmed by quantitative reverse transcriptase-polymerase chain reaction in 20 additional osteosarcoma patients. Accordingly, overexpression of miR-125b and miR-100 in three osteosarcoma cell lines enhanced cell proliferation, invasiveness, and resistance to chemotherapeutic drugs such as methotrexate, doxorubicin, and cisplatin. In addition, overexpression of miR-125b blocked the ability of these chemotherapy agents to induce apoptosis. As open biopsy is routinely performed to diagnose osteosarcoma, levels of miR-125b and miR-100 in these samples may be used as basis for risk stratification therapy. Daisuke Kubota, Nobuyoshi Kosaka, Tomohiro Fujiwara, Akihiko Yoshida, Yasuhito Arai, Zhiwei Qiao, Fumitaka Takeshita, Takahiro Ochiya, Akira Kawai, and Tadashi Kondo Copyright © 2016 Daisuke Kubota et al. All rights reserved. Phase II Trial of Angiotensin-(1-7) for the Treatment of Patients with Metastatic Sarcoma Tue, 08 Nov 2016 09:13:03 +0000 http://www.hindawi.com/journals/sarcoma/2016/4592768/ Background. Angiotensin-(1-7) [Ang-(1-7)] is an endogenous antiangiogenic hormone with anticancer activity. In a phase I study of Ang-(1-7), two of three patients with metastatic sarcoma experienced disease stabilization. This phase II study examined clinical and biomarker outcomes for patients with metastatic sarcoma. Methods. Ang-(1-7) was administered by subcutaneous injection at a dose of 20 mg daily. If excessive toxicities occurred in the first cohort, a dose deescalation cohort was allowed. Blood samples were obtained to measure changes in biomarkers. Results. Treatment was well-tolerated and the dose deescalation cohort was not required. Plasma PlGF concentrations following treatment were not statistically significantly changed. A significant increase in plasma Ang-(1-7) was observed at 4 hours after injection. The median progression-free survival was 2.7 months (95% CI; 1.4 to 4.1 months), and the median overall survival was 10.2 months (95% CI; 5.3 to 18.3 months). Two patients with vascular sarcomas demonstrated prolonged disease stabilization of 10 months (hemangiopericytoma) and 19 months (epithelioid hemangioendothelioma). Conclusions. Ang-(1-7) at a dose of 20 mg daily was well-tolerated. This prospective phase II study failed to confirm the PlGF biomarker effect identified in the prior phase I study. Prolonged disease stabilization in hemangiopericytoma and epithelioid hemangioendothelioma may warrant further investigation. Paul D. Savage, James Lovato, K. Bridget Brosnihan, Antonius A. Miller, and W. Jeffrey Petty Copyright © 2016 Paul D. Savage et al. All rights reserved. Trabectedin Followed by Irinotecan Can Stabilize Disease in Advanced Translocation-Positive Sarcomas with Acceptable Toxicity Mon, 24 Oct 2016 13:15:08 +0000 http://www.hindawi.com/journals/sarcoma/2016/7461783/ Background. Preclinical data indicate that trabectedin followed by irinotecan has strong synergistic effects on Ewing sarcoma. This is presumably due to hypersensitization of the tumor cells to the camptothecin as an effect of trabectedin in addition to synergistic suppression of EWS-FLI1 downstream targets. A strong effect was also reported in a human rhabdomyosarcoma xenograft. Procedure. Twelve patients with end-stage refractory translocation-positive sarcomas were treated with trabectedin followed by irinotecan within a compassionate use program. Eight patients had Ewing sarcoma and four patients had other translocation-positive sarcomas. Results. Three-month survival rate was 0.75 after the start of this therapy. One patient achieved a partial response according to RECIST criteria, five had stable disease, and the remaining six progressed through therapy. The majority of patients experienced significant hematological toxicity (grades 3 and 4). Reversible liver toxicity and diarrhea also occurred. Conclusions. Our experience with the combination of trabectedin followed with irinotecan in patients with advanced sarcomas showed promising results in controlling refractory solid tumors. While the hematological toxicity was significant, it was reversible. Quality of life during therapy was maintained. These observations encourage a larger clinical trial. J. Herzog, F. von Klot-Heydenfeldt, S. Jabar, A. Ranft, C. Rossig, U. Dirksen, J. Van den Brande, M. D’Incalci, I. von Luettichau, P. J. Grohar, W. E. Berdel, and St. Burdach Copyright © 2016 J. Herzog et al. All rights reserved. Axitinib Has Antiangiogenic and Antitumorigenic Activity in Myxoid Liposarcoma Sun, 16 Oct 2016 15:15:42 +0000 http://www.hindawi.com/journals/sarcoma/2016/3484673/ Myxoid liposarcoma is a rare form of soft-tissue sarcoma. Although most patients initially respond well to treatment, approximately 21% relapse, highlighting the need for alternative treatments. To identify novel treatment regimens and gain a better understanding of myxoid liposarcoma tumor biology, we screened various candidate and approved targeted therapeutics and chemotherapeutics against myxoid liposarcoma cell lines. Therapeutics that target angiogenesis showed antitumor activity. The small molecule inhibitor axitinib, which targets angiogenesis by inhibiting the VEGFR and PDGFR families and c-Kit, inhibited cell cycle progression and induced apoptosis in vitro, as well as having significant antitumor activity against MLS 1765 myxoid liposarcoma xenografts in mice. Axitinib also displayed synergistic antitumor activity in vitro when combined with the potassium channel ionophore salinomycin or the BH3 mimetic ABT-737. Another angiogenesis-targeting therapeutic, 4EGI-1, which targets the oncoprotein eIF4E, significantly decreased angiogenic ligand expression by myxoid liposarcoma cells and reduced tumor cell growth. To verify this oncogenic addiction to angiogenic pathways, we utilized VEGFR-derived ligand traps and found that autocrine VEGFR signaling was crucial to myxoid liposarcoma cell survival. Overall, these findings suggest that autocrine angiogenic signaling through the VEGFR family is critical to myxoid liposarcoma cell survival and that further study of axitinib as a potential anticancer therapy is warranted. Lauren T. Kerr, Jacqueline F. Donoghue, Alexander L. Wilding, and Terrance G. Johns Copyright © 2016 Lauren T. Kerr et al. All rights reserved. The Discrepancy between Patient and Clinician Reported Function in Extremity Bone Metastases Tue, 20 Sep 2016 07:34:10 +0000 http://www.hindawi.com/journals/sarcoma/2016/1014248/ Background. The Musculoskeletal Tumor Society (MSTS) scoring system measures function and is commonly used but criticized because it was developed to be completed by the clinician and not by the patient. We therefore evaluated if there is a difference between patient and clinician reported function using the MSTS score. Methods. 128 patients with bone metastasis of the lower () and upper () extremity completed the MSTS score. The MSTS score consists of six domains, scored on a 0 to 5 scale and transformed into an overall score ranging from 0 to 100% with a higher score indicating better function. The MSTS score was also derived from clinicians’ reports in the medical record. Results. The median age was 63 years (interquartile range [IQR]: 55–71) and the study included 74 (58%) women. We found that the clinicians’ MSTS score (median: 65, IQR: 49–83) overestimated the function as compared to the patient perceived score (median: 57, IQR: 40–70) by 8 points (). Conclusion. Clinician reports overestimate function as compared to the patient perceived score. This is important for acknowledging when informing patients about the expected outcome of treatment and for understanding patients’ perceptions. Stein J. Janssen, Eva A. J. van Rein, Nuno Rui Paulino Pereira, Kevin A. Raskin, Marco L. Ferrone, Francis J. Hornicek, Santiago A. Lozano-Calderon, and Joseph H. Schwab Copyright © 2016 Stein J. Janssen et al. All rights reserved. Molecular Targets and Emerging Therapeutic Options for Uterine Leiomyosarcoma Mon, 19 Sep 2016 14:18:00 +0000 http://www.hindawi.com/journals/sarcoma/2016/7018106/ Uterine leiomyosarcoma (uLMS) is an aggressive malignancy characterized by its early metastasis, high rates of recurrence, and poor prognosis. Multiple obstacles complicate the clinical management of uLMS. These include the fact that most uLMS are typically identified only after a woman has undergone hysterectomy or myomectomy, the limited efficacy of adjuvant therapy for early stage disease, and the poor response of metastatic disease to current treatments. Here, we discuss recent insights into the molecular basis of uLMS and discuss emerging options for its clinical management. Particular attention is given to the biologic basis of these strategies with the goal of understanding the rationale motivating their use. Heather Miller, Chiemeka Ike, Jennifer Parma, Ramya P. Masand, Claire M. Mach, and Matthew L. Anderson Copyright © 2016 Heather Miller et al. All rights reserved. Current Immunotherapies for Sarcoma: Clinical Trials and Rationale Wed, 14 Sep 2016 13:14:35 +0000 http://www.hindawi.com/journals/sarcoma/2016/9757219/ Sarcoma tumors are rare and heterogeneous, yet they possess many characteristics that may facilitate immunotherapeutic responses. Both active strategies including vaccines and passive strategies involving cellular adoptive immunotherapy have been applied clinically. Results of these clinical trials indicate a distinct benefit for select patients. The recent breakthrough of immunologic checkpoint inhibition is being rapidly introduced to a variety of tumor types including sarcoma. It is anticipated that these emerging immunotherapies will exhibit clinical efficacy for a variety of sarcomas. The increasing ability to tailor immunologic therapies to sarcoma patients will undoubtedly generate further enthusiasm and clinical research for this treatment modality. Demytra Mitsis, Valerie Francescutti, and Joseph Skitzki Copyright © 2016 Demytra Mitsis et al. All rights reserved. HIV-1 Evolutionary Patterns Associated with Metastatic Kaposi’s Sarcoma during AIDS Mon, 29 Aug 2016 08:47:09 +0000 http://www.hindawi.com/journals/sarcoma/2016/4510483/ Kaposi’s sarcoma (KS) in HIV-infected individuals can have a wide range of clinical outcomes, from indolent skin tumors to a life-threatening visceral cancer. KS tumors contain endothelial-related cells and inflammatory cells that may be HIV-infected. In this study we tested if HIV evolutionary patterns distinguish KS tumor relatedness and progression. Multisite autopsies from participants who died from HIV-AIDS with KS prior to the availability of antiretroviral therapy were identified at the AIDS and Cancer Specimen Resource (ACSR). Two patients (KS1 and KS2) died predominantly from non-KS-associated disease and KS3 died due to aggressive and metastatic KS within one month of diagnosis. Skin and visceral tumor and nontumor autopsy tissues were obtained (). Single genome sequencing was used to amplify HIV RNA and DNA, which was present in all tumors. Independent HIV tumor clades in phylogenies differentiated KS1 and KS2 from KS3, whose sequences were interrelated by both phylogeny and selection. HIV compartmentalization was confirmed in KS1 and KS2 tumors; however, in KS3, no compartmentalization was observed among sampled tissues. While the sample size is small, the HIV evolutionary patterns observed in all patients suggest an interplay between tumor cells and HIV-infected cells which provides a selective advantage and could promote KS progression. Susanna L. Lamers, Rebecca Rose, David J. Nolan, Gary B. Fogel, Andrew E. Barbier, Marco Salemi, and Michael S. McGrath Copyright © 2016 Susanna L. Lamers et al. All rights reserved. Ewing’s Sarcoma as a Second Malignancy in Long-Term Survivors of Childhood Hematologic Malignancies Mon, 25 Jul 2016 07:11:22 +0000 http://www.hindawi.com/journals/sarcoma/2016/5043640/ Modern multimodal treatment has significantly increased survival for patients affected by hematologic malignancies, especially in childhood. Following remission, however, the risk of developing a further malignancy is an important issue. The long-term estimated risk of developing a sarcoma as a secondary malignancy is increased severalfold in comparison to the general population. Ewing’s sarcoma family encompasses a group of highly aggressive, undifferentiated, intra- and extraosseous, mesenchymal tumors, caused by several types of translocations usually involving the EWSR1 gene. Translocation associated sarcomas, such as Ewing sarcoma, are only rarely encountered as therapy associated secondary tumors. We describe the clinical course and management of three patients from a single institution with Ewing’s sarcoma that followed successfully treated lymphoblastic T-cell leukemia or non-Hodgkin lymphoma. The literature on secondary Ewing’s sarcoma is summarized and possible pathogenic mechanisms are critically discussed. Fabian Wolpert, Michael A. Grotzer, Felix Niggli, Dieter Zimmermann, Elisabeth Rushing, and Beata Bode-Lesniewska Copyright © 2016 Fabian Wolpert et al. All rights reserved. A Systematic Literature Review of Adverse Events Associated with Systemic Treatments Used in Advanced Soft Tissue Sarcoma Tue, 19 Jul 2016 13:25:06 +0000 http://www.hindawi.com/journals/sarcoma/2016/3597609/ This systematic literature review describes adverse events (AEs) among patients with soft tissue sarcoma (STS) who received second-line or later anticancer therapies. Searches were conducted in PubMed, EMBASE, and Cochrane Central Register of Controlled Trials for studies of adults with advanced or metastatic STS who received systemic anticancer therapy before enrollment in a randomized-controlled trial of pazopanib, another targeted cancer agent, or cytotoxic chemotherapy. Of 204 publications identified, seven articles representing six unique studies met inclusion criteria. Additional safety results for pazopanib were identified on ClinicalTrials.gov. Hematologic toxicities were common with all therapies evaluated (pazopanib, trabectedin, dacarbazine ± gemcitabine, gemcitabine ± docetaxel, cyclophosphamide, and ifosfamide). Studies differed in AE type, timing of assessment, and outcomes reported, although patient populations and AE assessment timing were relatively similar for pazopanib and trabectedin. AEs that were more common with trabectedin than pazopanib were anemia, neutropenia, nausea/vomiting, and elevations in aspartate aminotransferase and alanine aminotransferase. An AE that was more common with pazopanib than trabectedin was anorexia. Only the pazopanib study reported AE frequencies versus placebo. A planned meta-analysis was not feasible, as there was no common comparator. More well-designed studies that include common comparators are needed for comparison of safety effects among treatments for STS. Ann Colosia, Shahnaz Khan, Michelle D. Hackshaw, Alan Oglesby, James A. Kaye, and Jeffrey M. Skolnik Copyright © 2016 Ann Colosia et al. All rights reserved. Immediate versus Delayed Sarcoma Reconstruction: Impact on Outcomes Wed, 13 Jul 2016 09:58:58 +0000 http://www.hindawi.com/journals/sarcoma/2016/7972318/ Background. Sarcoma is a rare malignancy, and more recent management algorithms emphasize a multidisciplinary approach and limb salvage, which has resulted in an increase in overall survival and limb preservation. However, limb salvage has resulted in a higher rate of wound complications. Objective. To compare the complications between immediate and delayed (>three weeks) reconstruction in the multidisciplinary limb salvage sarcoma patient population. Methods. A ten-year retrospective review of patients who underwent sarcoma resection was performed. The outcome of interest was wound complication in the postoperative period based on timing of reconstruction. We defined infection as any infection requiring intravenous antibiotics, partial flap failure as any flap requiring a debridement or revision, hematoma/seroma as any hematoma/seroma requiring drainage, and wound dehiscence as a wound that was not completely intact by three weeks postoperatively. Results. 70 (17 delayed, 53 immediate) patients who underwent sarcoma resection and reconstruction met the inclusion criteria. Delayed reconstruction significantly increased the incidence of postoperative wound infection and wound dehiscence. There was no difference in partial or total flap loss, hematoma, or seroma between the two groups. Discussion and Conclusion. Immediate reconstruction results in decreased wound complications may reduce the morbidity associated with multidisciplinary treatment in the limb salvage sarcoma patient. Kyle J. Sanniec, Cristine S. Velazco, Lyndsey A. Bryant, Nan Zhang, William J. Casey III, Raman C. Mahabir, and Alanna M. Rebecca Copyright © 2016 Kyle J. Sanniec et al. All rights reserved.