Histiocyte predominant myocarditis resulting from the addition of interferon gamma to cyclophosphamide-based lymphodepletion for adoptive cellular therapy.

BACKGROUND: Adoptive cellular therapy (ACT) is a promising treatment for synovial sarcoma (SS) with reported response rates of over 50%. However, more work is needed to obtain deeper and more durable responses. SS has a 'cold' tumor immune microenvironment with low levels of major histocompatibility complex (MHC) expression and few T-cell infiltrates, which could represent a barrier toward successful treatment with ACT. We previously demonstrated that both MHC expression and T-cell infiltration can be increased using systemic interferon gamma (IFN-γ), which could improve the efficacy of ACT for SS. CASE PRESENTATION: We launched a phase I trial incorporating four weekly doses of IFN-γ in an ACT regimen of high-dose cyclophosphamide (HD Cy), NY-ESO-1-specific T cells, and postinfusion low-dose interleukin (IL)-2. Two patients were treated. While one patient had significant tumor regression and resultant clinical benefit, the other patient suffered a fatal histiocytic myocarditis. Therefore, this cohort was terminated for safety concerns. CONCLUSION: We describe a new and serious toxicity of immunotherapy from IFN-γ combined with HD Cy-based lymphodepletion and low-dose IL-2. While IFN-γ should not be used concurrently with HD Cy or with low dose IL-2, IFN-γ may still be important in sensitizing SS for ACT. Future studies should avoid using IFN-γ during the immediate period before/after cell infusion. TRIAL REGISTRATION NUMBERS: NCT04177021, NCT01957709, and NCT03063632.

Are Skin Fiducials Comparable to Bone Fiducials for Registration When Planning Navigation-assisted Musculoskeletal Tumor Resections in a Cadaveric Simulated Tumor Model?

BACKGROUND: To improve and achieve adequate bony surgical margins, surgeons may consider computer-aided navigation a promising intraoperative tool, currently applied to a relatively few number of patients in whom freehand resections might be challenging. Placing fiducials (markers) in the bone, identifying specific anatomical landmarks, and registering patients for navigated resections are time consuming. To reduce the time both preoperatively and intraoperatively, skin fiducials may offer an efficient and alternative method of navigation registration. QUESTIONS/PURPOSES: (1) Does preoperative navigation using skin fiducials for registration allow the surgeon to achieve margins similar to those from bone fiducial registration in a simulated lower extremity tumor resection model in cadavers? (2) Does the use of preoperative navigation using skin fiducials for registration allow the surgeon to achieve similar bony margins in pelvic resections of simulated tumors as those achieved in long-bone resections using only skin fiducials for navigation in a cadaver model? METHODS: Simulated bone tumor resections were performed in three fresh-frozen cadavers with intact pelvic and lower-extremity anatomy using navigation guidance. We placed 5-cm intraosseous cement simulated bone tumors in the proximal/distal femur (n = 12), and proximal/distal tibia (n = 12) and pelvis (supraacetabular; n = 6). After bone tumor implantation, CT images of the pelvis and lower extremities were obtained. Each planned osseous resection margin was set at 10 mm. Navigation registration was performed for each simulated tumor using bone and skin markers that act as a point of reference (fiducials). The simulated bone tumor was resected based on a resection line that was established with navigation, and the corresponding osseous margins were calculated after resection. These margins were determined by an orthopaedic surgeon who was blinded to resection planning by the removal of cancellous bone around the cement simulated tumor. The shortest distance was measured from the cement to the resection line. Smaller mean differences between planned and postoperative margins were considered accurate. Independent t-tests were conducted to assess measurement differences between planned and postoperative margins at the 95% CI. Bland-Altman analyses were conducted to compare the deviation in margin difference between planned and postoperative margins in skin and bone fiducial registration, respectively. RESULTS: In all, 84 total resection margins were measured with 48 long bone and 20 pelvic obtained with skin fiducials and 16 long bone obtained with bone fiducials. The planned mean margin was 10 mm for all long bone and pelvic resections. We found that skin fiducial and bone fiducial postoperative margins had comparable accuracy when resecting long bones (10 ± 2 mm versus 9 ± 2 mm, mean difference 1 [95% CI 0 to 2]; p = 0.16). Additionally, skin fiducial long bone postoperative margins were comparable in accuracy to pelvic supraacetabular postoperative margins obtained with skin fiducials (10 ± 2 mm versus 11 ± 3 mm, mean difference -1 mm [95% CI -3 to 1]; p = 0.22). When comparing the deviation in margin difference between planned and postoperative margins in skin and bone fiducial registration, 90% (61 of 68) of skin fiducial and 100% (16 of 16) bone fiducial postoperative margins fell within 2 SDs. CONCLUSIONS: In this pilot study, skin fiducial markers were easy to identify on the skin surface of the cadaver model and on CT images used to plan margins. This technique appears to be an accurate way to plan margins in this model, but it needs to be tested thoroughly in patients to determine if it may be a better clinical approach than with bone fiducials. CLINICAL RELEVANCE: The margins obtained using skin fiducials and bone fiducials for registration were similar and comparable in this pilot study with a very small effect size. Boundaries of the simulated tumors were not violated in any resections. Skin fiducials are easier to identify than bone fiducials (anatomic landmarks). If future clinical studies demonstrate that margins obtained using skin fiducials for registration are similar to margins obtained with anatomical landmarks, the use of navigation with skin fiducials instead of bone fiducials may be advantageous. This technique may decrease the surgeon's time used to plan for and localize registration points and offer an alternative registration technique, providing the surgeon with other registration approaches.

Intraosseous malignant peripheral nerve sheath tumor of the sacrum in a patient with neurofibromatosis type I.

Malignant intraosseous peripheral nerve sheath tumor is a very rare malignancy most commonly seen in patients with neurofibromatosis type 1. This tumor almost exclusively occurs in the maxillofacial region, with manifestation of this tumor in other regions of the skeleton infrequently reported. We describe a 23-year-old female with previously undiagnosed neurofibromatosis type 1 presenting with lower extremity weakness, paresthesias, and bowel/bladder symptoms. The patient had an aneurysmal lytic bone lesion centered in the upper sacrum with invasion of the L5 vertebral body. On MRI, the lesion was homogeneously isointense to muscle on T1, heterogeneously hyperintense to muscle on T2, and demonstrated homogeneously avid contrast enhancement. Multiple additional small lesions with similar imaging characteristics were identified in the paraspinal soft tissues. Low grade malignant peripheral nerve sheath tumor of the sacrum was diagnosed on biopsy. The patient was treated with sacral resection and radiation therapy for local disease control.

MRI Identification of the Osseous Extent of Pediatric Bone Sarcomas.

BACKGROUND: The quantitative accuracy of MRI in predicting the intraosseous extent of primary sarcoma of bone has not been definitively confirmed, although MRI is widely accepted as an accurate tool to plan limb salvage resections. Because inaccuracies in MRI determination of tumor extent could affect the ability of a tumor surgeon to achieve negative margins and avoid local recurrence, we thought it important to assess the accuracy of MR-determined tumor extent to the actual extent observed pathologically from resected specimens in pediatric patients treated for primary sarcomas of bone. QUESTIONS/PURPOSES: (1) Does the quantitative pathologic bony margin correlate with that measured on preoperative MRI? (2) Are T1- or T2-weighted MRIs most accurate in determining a margin? (3) Is there a difference in predicting tumor extent between MRI obtained before or after neoadjuvant chemotherapy and which is most accurate? METHODS: We retrospectively studied a population of 211 potentially eligible patients who were treated with limb salvage surgery between August 1999 and July 2015 by a single surgeon at a single institution for primary sarcoma of bone. Of 131 patients (62%) with disease involving the femur or tibia, 107 (51%) were classified with Ewing's sarcoma or osteosarcoma. Records were available for review in our online database for 79 eligible patients (37%). Twenty-six patients (12%) were excluded because of insufficient or unavailable clinical or pathology data and 17 patients (8%) were excluded as a result of inadequate or incomplete MR imaging, leaving 55 eligible participants (26%) in the final cohort. The length of the resected specimen was superimposed on preresection MRI sequences to compare the margin measured by MRI with the margin measured by histopathology. Arithmetic mean differences and Pearson r correlations were used to assess quantitative accuracy (size of the margin). RESULTS: All MR imaging types were positively associated with final histopathologic margin. T1-weighted MRI after neoadjuvant chemotherapy and final histopathologic margin had the strongest positive correlation of all MR imaging and time point comparisons (r = 0.846, p < 0.001). Mean differences existed between the normal marrow margin on T1-weighted MRI before neoadjuvant chemotherapy (t = 8.363; mean, 18.883 mm; 95% confidence interval [CI], 14.327-23.441; p < 0.001), T2-weighted MRI before neoadjuvant chemotherapy (t = 8.194; mean, 17.204 mm; 95% CI, 12.970-21.439; p < 0.001), T1-weighted after neoadjuvant chemotherapy (t = 10.808; mean, 22.178 mm; 95% CI, 18.042-26.313; p < 0.001), T2-weighted after neoadjuvant chemotherapy (t = 10.702; mean, 20.778 mm; 95% CI, 16.865-24.691; p < 0.001), and the final histopathologic margin. T1-weighted MRI after neoadjuvant chemotherapy compared with the final histopathologic margin had the smallest mean difference in MRI-measured versus histopathologic margin size (mean, 5.9 mm; SD = 4.5 mm). CONCLUSIONS: T1 MRI after neoadjuvant chemotherapy exhibited the strongest positive correlation and smallest mean difference compared with histopathologic margin. When planning surgical resections based on MRI obtained after neoadjuvant chemotherapy, for safety, one should account for a potential difference between the apparent margin of a tumor on an MRI and the actual pathologic margin of that tumor of up to 1 cm. LEVEL OF EVIDENCE: Level III, diagnostic study.

Injection of Unicameral Bone Cysts with Bone Marrow Aspirate and Demineralized Bone Matrix Avoids Open Curettage and Bone Grafting in a Retrospective Cohort.

BACKGROUND: Many treatment options exist for unicameral bone cysts (UBC), without clear evidence of superiority. Meta-analyses have been limited by small numbers of patients in specific anatomic and treatment subgroups. The purpose of this study was to report the outcomes of injecting bone marrow aspirate and demineralized bone matrix (BMA/DBM) for the treatment of proximal humerus UBC. METHODS: Fifty-one patients with proximal humerus lesions treated by BMA/DBM injection were retrospectively reviewed from a single academic medical center. RESULTS: The mean number of injections performed per patient was 2.14 (range 1-5). Eleven patients underwent only one injection (22%), an additional 19 patients completed treatment after two injections (37%), four patients healed after three injections (8%), and one patient healed after four injections (2%). The cumulative success rate of serial BMA/DBM injections was 22% (11/51), 58% (30/51), 67% (34/51), and 69% (35/51). Eleven patients (22%) ultimately underwent open curettage and bone grafting, and five patients (10%) were treated with injection of calcium phosphate bone substitute. CONCLUSION: A BMA/DBM injection strategy avoided an open procedure in 78% of patients with a proximal humerus UBC. The majority of patients underwent at least 2 injection treatments. LEVEL OF EVIDENCE: Level IV retrospective cohort study.

Accuracy and Precision of a Surgical Navigation System: Effect of Camera and Patient Tracker Position and Number of Active Markers.

INTRODUCTION: Surgical navigation systems are increasingly used to aid resection and reconstruction of osseous malignancies. In the process of implementing image-based surgical navigation systems, there are numerous opportunities for error that may impact surgical outcome. This study aimed to examine modifiable sources of error in an idealized scenario, when using a bidirectional infrared surgical navigation system. MATERIALS AND METHODS: Accuracy and precision were assessed using a computerized-numerical-controlled (CNC) machined grid with known distances between indentations while varying: 1) the distance from the grid to the navigation camera (range 150 to 247cm), 2) the distance from the grid to the patient tracker device (range 20 to 40cm), and 3) whether the minimum or maximum number of bidirectional infrared markers were actively functioning. For each scenario, distances between grid points were measured at 10-mm increments between 10 and 120mm, with twelve measurements made at each distance. The accuracy outcome was the root mean square (RMS) error between the navigation system distance and the actual grid distance. To assess precision, four indentations were recorded six times for each scenario while also varying the angle of the navigation system pointer. The outcome for precision testing was the standard deviation of the distance between each measured point to the mean three-dimensional coordinate of the six points for each cluster. RESULTS: Univariate and multiple linear regression revealed that as the distance from the navigation camera to the grid increased, the RMS error increased (p<0.001). The RMS error also increased when not all infrared markers were actively tracking (p=0.03), and as the measured distance increased (p<0.001). In a multivariate model, these factors accounted for 58% of the overall variance in the RMS error. Standard deviations in repeated measures also increased when not all infrared markers were active (p<0.001), and as the distance between navigation camera and physical space increased (p=0.005). Location of the patient tracker did not affect accuracy (0.36) or precision (p=0.97). CONCLUSION: In our model laboratory test environment, the infrared bidirectional navigation system was more accurate and precise when the distance from the navigation camera to the physical (working) space was minimized and all bidirectional markers were active. These findings may require alterations in operating room setup and software changes to improve the performance of this system.

Malignant Transformation of Synovial Chondromatosis: A Systematic Review.

BACKGROUND: Synovial chondromatosis (SCh) can undergo malignant transformation. Pathologic diagnosis of secondary synovial chondrosarcoma (SChS) is challenging and misdiagnosis may result in over- or undertreatment. METHOD: A systematic review revealed 48 cases of SChS published in 27 reports since 1957. Data was collected to identify findings indicative of SChS and outcomes of treatment. RESULTS: At median follow-up of 18 months, patients were reported as alive (10%), alive without disease (22%), alive with disease (15%), dead of disease (19%), dead of pulmonary embolism (4%), and unknown (29%). Initial diagnosis of SChS (grade: low/unknown 48%, intermediate/high 52%) was after biopsy in 58%, local resection in 29%, and amputation in 13%. Seventy-four percent of patients underwent 1.8 (mean) resections. Patients treated prior to 1992 were managed with amputation in 79% of cases compared to 48% after 1992. Symptoms were present for 72 mos prior to diagnosis of SChS. Synovial chondrosarcoma demonstrated symptom progression over several months (82%), rapid recurrence after complete resection (30%), and medullary canal invasion (43%). The SChS tumor dimensions were seldom quantified. CONCLUSION: Malignant degeneration of synovial chondromatosis is rare but can necessitate morbid surgery or result in death. Pathognomonic signs for SChS including intramedullary infiltration are present in the minority of cases. Progression of symptoms, quick local recurrence, and muscle infiltration are more suggestive of SChS. Periarticular cortical erosion, extra-capsular extension, and metaplastic chondroid features are non-specific. Although poorly documented for SChS, tumor size is a strong indicator of malignancy. Biopsy and partial resection are prone to diagnostic error. Surgical decisions are frequently based on size and clinical appearance and may be in conflict with pathologic diagnosis.

Allograft Reconstruction for Sarcomas of the Tibia.

BACKGROUND: Allograft reconstruction of oncologic resections involving the tibia can have unpredictable results. Prior studies have reported a high rate of complications and a long recovery period involving prolonged bracing, repeated procedures and extended periods of antibiotics. METHODS: The case details of 30 tibial allografts (12 adults, 18 children; 20 intercalary, 7 hemicortical, 3 other) were reviewed retrospectively. Based on factors including function, pain, healing and infection, clinical outcomes were stratified into three categories: excellent, moderate, and poor. RESULTS: The overall survival rate of the allografts was 66% at a mean follow-up of 42 mos (adults) and 63 mos (children). Healing for metaphyseal junctions was successful in 73% at a mean of 44 weeks and for diaphyseal junctions, 64% at 41 weeks. Intercalary allografts in adults (4 of 20) all became infected and none had excellent results. All hemicortical allografts were performed in adults and 6 of 7 had excellent results. Distal intercalary allografts in children (6 of 20) had either excellent or moderate results with no infections, but had 3 nonunions and 2 fractures. Proximal intercalary allografts in children (8 of 20) had 2 excellent results, but had 6 infections requiring a cement spacer. Five of the six spacers were ultimately revised to another allograft or an arthroplasty. CONCLUSION: For tibial allograft reconstruction, surgeons and patients should prepare for a prolonged treatment course that may include multiple complications and surgeries. Excellent or moderate results can be achieved eventually in most, but amputation may be necessary in 15-20% of cases.

Surgical Release of Severe Flexion Contracture for Oncologic Knee Arthroplasty.

BACKGROUND: Severe postoperative knee contractures after arthroplasty or megaprosthesis reconstruction occur rarely, but are devastating complications. Management of preoperative flexion contractures is well-described, but there is a paucity of literature for surgical treatment of postoperative contractures. A retrospective chart review was performed for a single surgeon of cases between 1996 and 2014. RESULTS: Nine patients (5 of 66 for pediatrics; 4 of 95 for adults) underwent surgical release for severe stiffness after implantation of knee megaprosthesis. The total arc of motion was improved from a preoperative mean of 34° (range, 10° to 70°) to a postoperative mean 89° (63° to 125°). The amount of extension improved by a mean of 27° (range, -3° to +70°) and the amount of flexion improved by a mean of 28° (range, -10° to +75°). CONCLUSION: Surgical release of severe postoperative knee contracture is a challenging procedure, but in most cases, the amount of extension and flexion can be improved, yielding a greater total arc of motion.

Can a Made-for-Consumer Activity Monitor Assess Physical Activity in Adolescents and Young Adults After Lower Extremity Limb Salvage for Osseous Tumors?

BACKGROUND: The purpose of this study was to test the validity of a consumer-oriented activity monitor in adolescents and young adults undergoing limb salvage for primary bone malignancies. METHODS: A cross-sectional population of participants with an average age of 16 (range 12 to 22) years produced 472 days of activity monitoring during 25 evaluations periods alongside patient-reported outcome measures. RESULTS: Average daily steps ranged from 557 to 12,756 (mean=4711) and was moderately associated with the short-form (SF) 36 physical component subscale (r=0.46, P=0.04) as well as the SF6D health state utility measure (r=0.48, P=0.04), but not the SF36 mental component subscale (P=0.66) or Toronto extremity salvage score (P=0.07). Time from surgery was strongly correlated with average daily steps (r=0.7, P<0.001). CONCLUSIONS: A made-for-consumer activity monitor provided real-world data regarding the outcome of adolescent and young adult limb salvage, and evidence of validity in this population. Such lower cost, user-friendly devices may facilitate assessment of free-living activity and allow novel comparisons of treatment strategies. LEVEL OF EVIDENCE: Level II-diagnostic.

Soft Tissue Sarcoma, Version 2.2016, NCCN Clinical Practice Guidelines in Oncology.

Soft tissue sarcomas (STS) are rare solid tumors of mesenchymal cell origin that display a heterogenous mix of clinical and pathologic characteristics. STS can develop from fat, muscle, nerves, blood vessels, and other connective tissues. The evaluation and treatment of patients with STS requires a multidisciplinary team with demonstrated expertise in the management of these tumors. The complete NCCN Guidelines for Soft Tissue Sarcoma (available at NCCN.org) provide recommendations for the diagnosis, evaluation, and treatment of extremity/superficial trunk/head and neck STS, as well as intra-abdominal/retroperitoneal STS, gastrointestinal stromal tumor, desmoid tumors, and rhabdomyosarcoma. This manuscript discusses guiding principles for the diagnosis and staging of STS and evidence for treatment modalities that include surgery, radiation, chemoradiation, chemotherapy, and targeted therapy.

The effect of surgery with radiation on pelvic Ewing sarcoma survival.

BACKGROUND: Pelvic Ewing sarcoma (ES) has poorer outcomes than extremity-based lesions and the method of local control is controversial. METHODS: A retrospective review was performed of 40 primary pelvic or sacral ES treated by a single surgeon. All received modern chemotherapy and those that received radiation were treated with modern dosages. RESULTS: Fifty-five percent were disease-free at latest follow-up (median, 83.1 mos). Sixty-one percent had ≥ 99% necrosis, which was associated with 65% disease-free survival. Larger size (P = 0.016) and the absence of metastatic disease (P = 0.005) was predictive of survival. Eighty-three percent of relapsed patients were DOD. Half of patients who received surgery alone or RT alone have NED while 57% of those who received S/RT have NED. Complication rates were 69% (S/RT), 75% (surgery alone), 10% (RT alone). Functional outcomes were similar. CONCLUSION: Primary pelvic ES is localized at presentation in 50% and the absence of metastases is the strongest predictor for survival. Chemotherapy is key, but excellent histologic response is neither a guarantee nor a necessity for survival. More than one-third die despite an excellent histologic response and at least one-third with lung metastases survive. With chemotherapy, radiation, and surgery, reasonable control of disease can be achieved. LEVEL OF EVIDENCE III: Case-control or retrospective cohort study.

Assessment of registration accuracy during computer-aided oncologic limb-salvage surgery.

PURPOSE: Computer-aided surgery is used in musculoskeletal tumor procedures to improve the surgeon's orientation to local anatomy during tumor resection. For the navigation system to function correctly, preoperative imaging (e.g., CT, MR) must be registered to the patient in the operating room. The goals of this study were (1) to directly quantify registration accuracy in computer-aided tumor surgery and (2) to validate the "system reported error" (SRE) of the navigation system. METHODS: Registration accuracy was evaluated in eight bone sarcoma cases by determining the location of the anatomical paired-points used for registration following surface matching. Coordinates of specific intraoperative post-registration points were compared with the corresponding coordinates in preoperative CT scans to determine the measurement error (ME). RESULTS: The mean difference between post-registration points and planned registration points was 12.21±6.52 mm significantly higher than the mean SRE (0.68 ± 0.15 mm; p = 0.002; 95 % CI 6.11-16.96 mm). The SRE poorly correlated with the calculated ME (R(2) = 0.040). Anatomical paired-point registration with surface matching results in a substantial shift in the post-registration coordinates of the same paired-points used for registration, and this shift is not represented by the SRE. CONCLUSION: The SRE of a surgical navigation system was poorly correlated with direct measurements obtained in musculoskeletal tumor surgery. Improvement in registration accuracy is needed to better navigate tumor boundaries and ensure clear margins while maximally preserving the unaffected tissues and reducing operative morbidity.

Tetramer guided, cell sorter assisted production of clinical grade autologous NY-ESO-1 specific CD8(+) T cells.

BACKGROUND: Adoptive T cell therapy represents an attractive modality for the treatment of patients with cancer. Peripheral blood mononuclear cells have been used as a source of antigen specific T cells but the very low frequency of T cells recognizing commonly expressed antigens such as NY-ESO-1 limit the applicability of this approach to other solid tumors. To overcome this, we tested a strategy combining IL-21 modulation during in vitro stimulation with first-in-class use of tetramer-guided cell sorting to generate NY-ESO-1 specific cytotoxic T lymphocytes (CTL). METHODS: CTL generation was evaluated in 6 patients with NY-ESO-1 positive sarcomas, under clinical manufacturing conditions and characterized for phenotypic and functional properties. RESULTS: Following in vitro stimulation, T cells stained with NY-ESO-1 tetramer were enriched from frequencies as low as 0.4% to >90% after single pass through a clinical grade sorter. NY-ESO-1 specific T cells were generated from all 6 patients. The final products expanded on average 1200-fold to a total of 36 billion cells, were oligoclonal and contained 67-97% CD8(+), tetramer(+) T cells with a memory phenotype that recognized endogenous NY-ESO-1. CONCLUSION: This study represents the first series using tetramer-guided cell sorting to generate T cells for adoptive therapy. This approach, when used to target more broadly expressed tumor antigens such as WT-1 and additional Cancer-Testis antigens will enhance the scope and feasibility of adoptive T cell therapy.

Gastrointestinal stromal tumors, version 2.2014.

Gastrointestinal stromal tumors (GIST) are the most common soft tissue sarcoma of the gastrointestinal tract, resulting most commonly from KIT or platelet-derived growth factor receptor α (PDGFRα)-activating mutations. These NCCN Guideline Insights highlight the important updates to the NCCN Guidelines for Soft Tissue Sarcoma specific to the management of patients with GIST experiencing disease progression while on imatinib and/or sunitinib.

Validation of the SF-6D Health State Utilities Measure in Lower Extremity Sarcoma.

Aim. Health state utilities measures are preference-weighted patient-reported outcome (PRO) instruments that facilitate comparative effectiveness research. One such measure, the SF-6D, is generated from the Short Form 36 (SF-36). This report describes a psychometric evaluation of the SF-6D in a cross-sectional population of lower extremity sarcoma patients. Methods. Patients with lower extremity sarcoma from a prospective database who had completed the SF-36 and Toronto Extremity Salvage Score (TESS) were eligible for inclusion. Computed SF-6D health states were given preference weights based on a prior valuation. The primary outcome was correlation between the SF-6D and TESS. Results. In 63 pairs of surveys in a lower extremity sarcoma population, the mean preference-weighted SF-6D score was 0.59 (95% CI 0.4-0.81). The distribution of SF-6D scores approximated a normal curve (skewness = 0.11). There was a positive correlation between the SF-6D and TESS (r = 0.75, P < 0.01). Respondents who reported walking aid use had lower SF-6D scores (0.53 versus 0.61, P = 0.03). Five respondents underwent amputation, with lower SF-6D scores that approached significance (0.48 versus 0.6, P = 0.06). Conclusions. The SF-6D health state utilities measure demonstrated convergent validity without evidence of ceiling or floor effects. The SF-6D is a health state utilities measure suitable for further research in sarcoma patients.

Soft tissue sarcoma, version 2.2014.

These NCCN Guidelines Insights highlight the important updates to the NCCN Guidelines for Soft Tissue Sarcoma (STS) specific to the role of radiation therapy in the management of patients with retroperitoneal/intra-abdominal STS. The guidelines have also included recommendations for genetic testing and counseling for patients with a clinical and/or family history of genetic cancer syndromes associated with a predisposition for the development of STS.

Sarcoma mid-therapy [F-18]fluorodeoxyglucose positron emission tomography (FDG PET) and patient outcome.

BACKGROUND: Our previous research investigated the ability of [F-18]fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging results to predict outcome in patients with sarcoma. Tumor uptake of FDG before and after neoadjuvant chemotherapy was predictive of patient outcome. With this background, a prospective clinical study was designed to assess whether tumor FDG uptake levels in the middle of neoadjuvant chemotherapy added additional prognostic information to pre-therapy imaging data. METHODS: Sixty-five patients with either bone or soft-tissue sarcoma were treated with neoadjuvant-based chemotherapy according to the standard clinical practice for each tumor group. All patients had FDG PET studies before therapy, mid-therapy (after two cycles of chemotherapy), and before resection. Tumor FDG uptake (SUVmax, the maximum standardized uptake value) at each imaging time point, tumor type (bone or soft-tissue sarcoma), tumor size, and histopathologic grade were recorded for each patient. The time from the pre-therapy FDG PET study to events of local tumor recurrence, metastasis, or death were extracted from the clinical records for comparison with the imaging data. Univariate and multivariate analyses of the imaging and clinical data were performed. RESULTS: Univariate and multivariate data analyses showed that the difference (measured as the percentage reduction) between the pre-therapy and mid-therapy maximum tumor uptake values added prognostic value to patient outcome predictions independently of other patient variables. CONCLUSIONS: The utility of a tumor pre-therapy FDG PET scan as a biomarker for the outcome of patients with sarcoma was strengthened by a mid-therapy scan to evaluate the interim treatment response.

Soft tissue sarcoma, version 2.2012: featured updates to the NCCN guidelines.

The major changes to the 2012 and 2011 NCCN Guidelines for Soft Tissue Sarcoma pertain to the management of patients with gastrointestinal stromal tumors (GISTs) and desmoid tumors (aggressive fibromatosis). Postoperative imatinib following complete resection for primary GIST with no preoperative imatinib is now included as a category 1 recommendation for patients with intermediate or high risk of recurrence. The panel also reaffirmed the recommendation for preoperative use of imatinib in patients with GISTs that are resectable with negative margins but associated with significant surgical morbidity. Observation was included as an option for patients with resectable desmoid tumors that are small and asymptomatic, not causing morbidity, pain, or functional limitation. Sorafenib is included as an option for systemic therapy for patients with desmoid tumors.