Preoperative Radiotherapy in Patients With Primary Retroperitoneal Sarcoma: EORTC-62092 Trial (STRASS) Versus Off-trial (STREXIT) Results.

OBJECTIVE: The aim of the present study was to compare the effect of radiotherapy (RT) on abdominal recurrence-free survival (ARFS) in patients with primary retroperitoneal sarcoma treated in the EORTC-STBSG-62092 (STRASS) phase 3 randomized controlled trial (STRASS cohort) and off-trial (STREXIT cohort) and to pool STRASS and STREXIT data to test the hypothesis that RT improves ARFS in patients with liposarcoma. BACKGROUND: The STRASS trial did not show any difference in ARFS between patients treated with preoperative radiotherapy+surgery (RT+S) versus surgery alone (S). METHODS: All consecutive adult patients not enrolled in STRASS and underwent curative-intent surgery for a primary retroperitoneal sarcoma with or without preoperative RT between 2012 and 2017 (STRASS recruiting period) among ten STRASS-recruiting centres formed the STREXIT cohort. The effect of RT in STREXIT was explored with a propensity score (PS)-matching analysis. Primary endpoint was ARFS defined as macroscopically incomplete resection or abdominal recurrence or death of any cause, whichever occurred first. RESULTS: STRASS included 266 patients, STREXIT included 831 patients (727 after excluding patients who received preoperative chemotherapy, 202 after 1:1 PS-matching). The effect of RT on ARFS in STRASS and 1:1 PS-matched STREXIT cohorts, overall and in patients with liposarcoma, was similar. In the pooled cohort analysis, RT administration was associated with better ARFS in patients with liposarcoma [N=321, hazard ratio (HR), 0.61; 95% confidence interval (CI), 0.42-0.89]. In particular, patients with well-differentiated liposarcoma and G1-2 dedifferentiated liposarcoma (G1-2 DDLPS, n=266) treated with RT+S had better ARFS (HR, 0.63; 95% CI, 0.40-0.97) while patients with G3 DDLPS and leiomyosarcoma had not. At the current follow-up, there was no association between RT and overall survival or distant metastases-free survival. CONCLUSIONS: In this study, preoperative RT was associated with better ARFS in patients with primary well-differentiated liposarcoma and G1-2 DDLPS.

Distribution and Rate of Myxoid Liposarcoma Spine Metastases: Impact on Surveillance Imaging.

BACKGROUND: Myxoid liposarcoma (LPS) has a unique tendency to spread to extrapulmonary sites, including osseous sites such as the spine, and adjacent sites such as the paraspinous tissue. No clear consensus exists to guide the approach to imaging in these patients. OBJECTIVE: The aim of this study was to investigate the rate and distribution of spine metastases in patients with myxoid LPS and detection modality. METHODS: Records of all patients with myxoid LPS evaluated at our sarcoma center were retrospectively reviewed. Disease patterns and imaging modality utilization were analyzed. RESULTS: Between 2000 and 2020, 164 patients with myxoid LPS were identified. The majority (n = 148, 90%) presented with localized disease, with half (n = 82, 50%) of all patients developing metastases or recurrence during their disease course. With a median follow-up of 69.2 months, spine/paraspinous metastases developed in 38 patients (23%), of whom 35 (92%) already had synchronous, non-spine metastases. Spine disease was only visible on magnetic resonance imaging (MRI), as opposed to other imaging modalities, for over one-quarter of patients with spine metastases (n = 10). For patients with metastatic disease, spine metastases were associated with worse median overall survival (2.1 vs. 8.7 years, p < 0.001). CONCLUSION: Spine metastases occurred in nearly one-quarter of patients with myxoid LPS and represented an advanced disease state, as they primarily presented in the setting of synchronous, non-spine metastases, and were associated with worse overall survival. Routine surveillance with spine MRI in patients with localized disease likely provides no benefit but may be considered in those with known metastatic disease.

Management of Locally Recurrent Retroperitoneal Sarcoma in the Adult: An Updated Consensus Approach from the Transatlantic Australasian Retroperitoneal Sarcoma Working Group.

BACKGROUND: Surgery is the mainstay of treatment for retroperitoneal sarcoma (RPS), but local recurrence is common. Biologic behavior and recurrence patterns differ significantly among histologic types of RPS, with implications for management. The Transatlantic Australasian RPS Working Group (TARPSWG) published a consensus approach to primary RPS, and to complement this, one for recurrent RPS in 2016. Since then, additional studies have been published, and collaborative discussion is ongoing to address the clinical challenges of local recurrence in RPS. METHODS: An extensive literature search was performed, and the previous consensus statements for recurrent RPS were updated after review by TARPSWG members. The search included the most common RPS histologic types: liposarcoma, leiomyosarcoma, solitary fibrous tumor, undifferentiated pleomorphic sarcoma, and malignant peripheral nerve sheath tumor. RESULTS: Recurrent RPS management was evaluated from diagnosis to follow-up evaluation. For appropriately selected patients, resection is safe. Nomograms currently are available to help predict outcome after resection. These and other new findings have been combined with expert recommendations to provide 36 statements, each of which is attributed a level of evidence and grade of recommendation. In this updated document, more emphasis is placed on histologic type and clarification of the intent for surgical treatment, either curative or palliative. Overall, the fundamental tenet of optimal care for patients with recurrent RPS remains individualized treatment after multidisciplinary discussion by an experienced team with expertise in RPS. CONCLUSIONS: Updated consensus recommendations are provided to help guide decision-making for treatment of locally recurrent RPS and better selection of patients who would potentially benefit from surgery.

Role of Radiation Therapy in Retroperitoneal Sarcoma.

Retroperitoneal sarcoma comprises a small subset of all soft tissue sarcoma and includes various histopathologic subtypes, each with unique patterns of behavior and differential risks for local recurrence and hematogenous metastatic spread. The primary treatment modality is surgery, although even with complete macroscopic resection, recurrence is common. The rationale for the addition of radiotherapy to resection is to improve local control; however, the use of radiation therapy for retroperitoneal sarcoma is controversial, and existing data are suboptimal to guide management. Treatment decisions should be determined with multidisciplinary input and shared decision-making. When used in selected patients, radiation therapy should be delivered preoperatively; postoperative treatment is not recommended.

Ultra-rare sarcomas: A consensus paper from the Connective Tissue Oncology Society community of experts on the incidence threshold and the list of entities.

BACKGROUND: Among sarcomas, which are rare cancers, many types are exceedingly rare; however, a definition of ultra-rare cancers has not been established. The problem of ultra-rare sarcomas is particularly relevant because they represent unique diseases, and their rarity poses major challenges for diagnosis, understanding disease biology, generating clinical evidence to support new drug development, and achieving formal authorization for novel therapies. METHODS: The Connective Tissue Oncology Society promoted a consensus effort in November 2019 to establish how to define ultra-rare sarcomas through expert consensus and epidemiologic data and to work out a comprehensive list of these diseases. The list of ultra-rare sarcomas was based on the 2020 World Health Organization classification, The incidence rates were estimated using the Information Network on Rare Cancers (RARECARENet) database and NETSARC (the French Sarcoma Network's clinical-pathologic registry). Incidence rates were further validated in collaboration with the Asian cancer registries of Japan, Korea, and Taiwan. RESULTS: It was agreed that the best criterion for a definition of ultra-rare sarcomas would be incidence. Ultra-rare sarcomas were defined as those with an incidence of approximately ≤1 per 1,000,000, to include those entities whose rarity renders them extremely difficult to conduct well powered, prospective clinical studies. On the basis of this threshold, a list of ultra-rare sarcomas was defined, which comprised 56 soft tissue sarcoma types and 21 bone sarcoma types. CONCLUSIONS: Altogether, the incidence of ultra-rare sarcomas accounts for roughly 20% of all soft tissue and bone sarcomas. This confirms that the challenges inherent in ultra-rare sarcomas affect large numbers of patients.

Role of Radiation Therapy for Newly Diagnosed Retroperitoneal Sarcoma.

OPINION STATEMENT: Soft tissue sarcomas (STS) are rare, aggressive, and heterogenous tumors, comprising approximately 1% of adult cancers with over 50 different subtypes. The mainstay of treatment for retroperitoneal sarcomas (RPS) includes surgical resection. The addition of radiation therapy (RT), either preoperatively or postoperatively, has been used to potentially decrease the risk of local recurrence. The recently published results from STRASS (EORTC-STBSG 62092-22092), which randomized patients to receive or not receive preoperative radiation, indicate no abdominal recurrence-free survival benefit (primary endpoint) nor overall survival benefit to date from the addition of preoperative RT prior to surgical resection in patients with RPS. Keeping in mind caveats of subgroup analyses, the data show a significant reduction in local recurrence with radiation therapy in resected patients and non-significant trends toward improved abdominal recurrence-free survival in all patients and improved local control and abdominal recurrence-free survival in patients with liposarcoma and low-grade sarcoma. Given the high rate of local failure with surgery alone, it is possible that higher RT dose and/or selective RT dose painting may improve outcomes. Prior to treatment, the authors encourage multidisciplinary review and discussion of management options at a sarcoma center for patients with RPS. Selective use of RT may be considered for patients at high risk of local recurrence.

Preoperative radiotherapy plus surgery versus surgery alone for patients with primary retroperitoneal sarcoma (EORTC-62092: STRASS): a multicentre, open-label, randomised, phase 3 trial.

BACKGROUND: Unlike for extremity sarcomas, the efficacy of radiotherapy for retroperitoneal sarcoma is not established. The aim of this study was to evaluate the impact of preoperative radiotherapy plus surgery versus surgery alone on abdominal recurrence-free survival. METHODS: EORTC-62092 is an open-label, randomised, phase 3 study done in 31 research institutions, hospitals, and cancer centres in 13 countries in Europe and North America. Adults (aged ≥18 years) with histologically documented, localised, primary retroperitoneal sarcoma that was operable and suitable for radiotherapy, who had not been previously treated and had a WHO performance status and American Society of Anesthesiologists score of 2 or lower, were centrally randomly assigned (1:1), using an interactive web response system and a minimisation algorithm, to receive either surgery alone or preoperative radiotherapy followed by surgery. Randomisation was stratified by hospital and performance status. Radiotherapy was delivered as 50·4 Gy (in 28 daily fractions of 1·8 Gy) in either 3D conformal radiotherapy or intensity modulated radiotherapy, and the objective of surgery was a macroscopically complete resection of the tumour mass with en-bloc organ resection as necessary. The primary endpoint was abdominal recurrence-free survival, as assessed by the investigator, and was analysed in the intention-to-treat population. Safety was analysed in all patients who started their allocated treatment. This trial is registered with ClinicalTrials.gov, NCT01344018. FINDINGS: Between Jan 18, 2012 and April 10, 2017, 266 patients were enrolled, of whom 133 were randomly assigned to each group. The median follow-up was 43·1 months (IQR 28·8-59·2). 128 (96%) patients from the surgery alone group had surgery, and 119 (89%) patients in the radiotherapy and surgery group had both radiotherapy and surgery. Median abdominal recurrence-free survival was 4·5 years (95% CI 3·9 to not estimable) in the radiotherapy plus surgery group and 5·0 years (3·4 to not estimable) in the surgery only group (hazard ratio 1·01, 95% CI 0·71-1·44; log rank p=0·95). The most common grade 3-4 adverse events were lymphopenia (98 [77%] of 127 patients in the radiotherapy plus surgery group vs one [1%] of 128 patients in the surgery alone group), anaemia (15 [12%] vs ten [8%]), and hypoalbuminaemia (15 [12%] vs five [4%]). Serious adverse events were reported in 30 (24%) of 127 patients in the radiotherapy plus surgery group, and in 13 (10%) of 128 patients in the surgery alone group. One (1%) of 127 patients in the radiotherapy plus surgery group died due to treatment-related serious adverse events (gastropleural fistula), and no patients in the surgery alone group died due to treatment-related serious adverse events. INTERPRETATION: Preoperative radiotherapy should not be considered as standard of care treatment for retroperitoneal sarcoma. FUNDING: European Organisation for Research and Treatment of Cancer, and European Clinical Trials in Rare Sarcomas.

Extrameningeal solitary fibrous tumors-surgery alone or surgery plus perioperative radiotherapy: A retrospective study from the global solitary fibrous tumor initiative in collaboration with the Sarcoma Patients EuroNet.

BACKGROUND: Solitary fibrous tumor (SFT) is a rare mesenchymal malignancy. Although surgery is potentially curative, the local relapse risk is high after marginal resections. Given the lack of prospective clinical trial data, the objective of the current study was to better define the role of perioperative radiotherapy (RT) in various SFT presentations by location. METHODS: This was retrospective study performed across 7 sarcoma centers. Clinical information was retrieved from all adult patients with extrameningeal, primary, localized SFT who were treated between 1990 and 2018 with surgery alone (S) compared with those who also received perioperative RT (S+RT). Differences in treatment characteristics between subgroups were tested using analysis of variance statistics and propensity score matching. Local control and overall survival rates were calculated from the start of treatment until progression or death from any cause. RESULTS: Of all 549 patients, 428 (78%) underwent S, and 121 (22%) underwent S+RT. The median follow-up was 52 months. After correction for mitotic count and surgical margins, S+RT was significantly associated with a lower risk of local progression (hazard ratio, 0.19: P = .029), an observation further confirmed by propensity score matching (P = .012); however, this association did not translate into an overall survival benefit. CONCLUSIONS: The results from this retrospective study investigating perioperative RT in patients with primary extrameningeal SFT suggest that combining RT with surgery in the management of this patient population is significantly associated with a reduced risk of local failures, especially in patients who have less favorable resection margins and in those who have tumors with a high mitotic count.

Racial Differences in Extremity Soft Tissue Sarcoma Treatment in a Universally Insured Population.

BACKGROUND: In prior reports from population-based databases, black patients with extremity soft tissue sarcoma (ESTS) have lower reported rates of limb-sparing surgery and adjuvant treatment. The objective of this study was to compare the multimodality treatment of ESTS between black and white patients within a universally insured and equal-access health care system. METHODS: Claims data from TRICARE, the US Department of Defense insurance plan that provides health care coverage for 9 million active-duty personnel, retirees, and dependents, were queried for patients younger than 65 y with ESTS who underwent limb-sparing surgery or amputation between 2006 and 2014 and identified as black or white race. Multivariable logistic regression analysis was used to evaluate the impact of race on the utilization of surgery, chemotherapy, and radiation. RESULTS: Of the 719 patients included for analysis, 605 patients (84%) were white and 114 (16%) were black. Compared with whites, blacks had the same likelihood of receiving limb-sparing surgery (odds ratio [OR], 0.861; 95% confidence interval [95% CI], 0.284-2.611; P = 0.79), neoadjuvant radiation (OR, 1.177; 95% CI, 0.204-1.319; P = 0.34), and neoadjuvant (OR, 0.852; 95% CI, 0.554-1.311; P = 0.47) and adjuvant (OR, 1.211; 95% CI, 0.911-1.611; P = 0.19) chemotherapy; blacks more likely to receive adjuvant radiation (OR, 1.917; 95% CI, 1.162-3.162; P = 0.011). CONCLUSIONS: In a universally insured population, racial differences in the rates of limb-sparing surgery for ESTS are significantly mitigated compared with prior reports. Biologic or disease factors that could not be accounted for in this study may contribute to the increased use of adjuvant radiation among black patients.

Screening populations at high risk for soft tissue sarcoma and surveillance following soft tissue sarcoma resection.

Soft tissue sarcomas (STS) are a rare and diverse group of tumors that affect both adult and pediatric populations. This review discusses current screening recommendations for populations at increased risk for STS, including those with genetic predispositions. We also review surveillance guidelines for those at risk for recurrence following curative-intent surgery.

Amputation for Extremity Sarcoma: Contemporary Indications and Outcomes.

INTRODUCTION: Amputation for localized extremity sarcoma (ES), once the primary therapy, is now rarely performed. We reviewed our experience to determine why patients with sarcoma still undergo immediate or delayed amputation, identify differences based on amputation timing, and evaluate outcomes. METHODS: Records of patients with primary, nonmetastatic ES who underwent amputation at our institution from 2001 to 2011 were reviewed. Univariate analysis was performed, and survival outcomes were calculated. RESULTS: We categorized 54 patients into three cohorts: primary amputation (A1, n = 18, 33%), secondary amputation after prior limb-sparing surgery (A2, n = 22, 41%), and hand and foot sarcomas (HF, n = 14, 26%). Median age at amputation was 54 years (range 18-88 years). Common indications for amputation (> 40%) were loss of function, bone involvement, multiple compartment involvement, and large tumor size (A1); proximal location, joint involvement, neurovascular compromise, multiple compartment involvement, multifocal or fungating tumor, loss of function, and large tumor size (A2); and joint involvement and prior unplanned surgery (HF). There was no difference in disease-specific survival (DSS) (p = 0.19) or metastasis-free survival (MFS) (p = 0.31) between early (A1) and delayed (A2) amputation. Compared with cohorts A1/A2, HF patients had longer overall survival (OS) (p = 0.04). CONCLUSIONS: Indications for amputation for extremity sarcoma vary between those who undergo primary amputation, delayed amputation, and amputation for hand or foot sarcoma. Amputations chosen judiciously are associated with excellent disease control and survival. For patients who ultimately need amputation, timing (early vs. delayed) does not affect survival.

Surgical Management of Primary Retroperitoneal Sarcomas: Rationale for Selective Organ Resection.

BACKGROUND: Recently, some have argued for routine resection of adjacent but uninvolved organs in patients with retroperitoneal sarcoma (RPS) without stipulating the rationale for such organ resection (beyond the need to achieve a macroscopically complete resection) or examining histopathologic organ invasion (HOI). This study reviewed the authors' experience with primary RPS to investigate the rate and rationale for individual organ resection and the rate of HOI. METHODS: Operative and pathology reports for patients with primary RPS who underwent resection at our institution were retrospectively reviewed. Histopathologic organ invasion was confirmed by a dedicated sarcoma pathologist. RESULTS: From 2002 through 2011, 118 patients underwent resection of a primary RPS, and 99 of these patients (84%) had at least one organ resected. Kidney (n = 57), colon (n = 51), and adrenal (n = 41) were the most commonly resected organs. For the 302 organs removed, the perioperative clinical rationale for the resection was suspected invasion or tumor origin (n = 52, 17%), involved end-organ vasculature (n = 39, 13%), organ encasement (n = 42, 14%), tumor adherence (n = 127, 42%), resection required for R0/R1 resection (n = 25, 8%), or other (n = 17, 6%). The presence of HOI was found in 77 (25%) of the 302 organs resected. In the reviewed studies, HOI was identified in 34 (65%) of 52 organs suspected of invasion or tumor origin, in 19% of organs resected due to tumor encasement, and in 26% of organs with adherent tumor, even when not suspected intraoperatively, but was never identified in organs resected purely as part of a liberal en bloc resection of adjacent organs. When invasion was suspected intraoperatively, HOI was confirmed in 50, 78, and 100% of resected organs respectively for well-dedifferentiated liposarcoma, dedifferentiated liposarcoma (DDLPS), and leiomyosarcoma (LMS). CONCLUSIONS: Histologic organ invasion was observed more commonly in organs resected with suspicion of invasion than in organs resected simply to achieve a negative margin, although this reflects a degree of subjectivity and selection bias. In more than one-fourth of adherent organs, HOI was present even when not suspected intraoperatively. Histologic subtype may predict HOI because DDLPS and LMS are associated with high rates of HOI when invasion is suspected intraoperatively. Development of a data-driven, histology-specific rationale for adjacent organ resection is critical.

Radiation therapy in retroperitoneal sarcoma management.

Surgery is potentially curative for primary non-metastatic retroperitoneal soft tissue sarcomas (RPS), although patients remain at risk for local recurrence. To reduce this risk, the addition of radiotherapy to radical surgery may be considered. Nevertheless, level I evidence to support radiotherapy is currently lacking. The results from the EORTC-STBSG 62092-22092 studying this question are awaited. This manuscript addresses issues to consider when radiation-oncologists engage in a multidisciplinary treatment approach for RPS patients, including radiotherapy.

Localized Adult Ewing Sarcoma: Favorable Outcomes with Alternating Vincristine, Doxorubicin, Cyclophosphamide, and Ifosfamide, Etoposide (VDC/IE)-Based Multimodality Therapy.

BACKGROUND: In children with localized Ewing sarcoma (ES), addition of ifosfamide and etoposide to cyclophosphamide, doxorubicin, and vincristine (VDC/IE) improved 5-year overall survival (OS) to 70%-80%. Prior to delivery of VDC/IE in adults, 5-year OS was <50%. We reviewed our institutional outcomes for adults with ES who received VDC/IE-based treatment. MATERIALS AND METHODS: Between 1997-2013, 67 adults with localized ES were treated with curative intent. Local recurrence-free survival (LRFS), progression-free survival (PFS), and OS were determined using Kaplan-Meier method; comparisons were assessed with log-rank. Proportional hazard models were used to determine predictive factors. RESULTS: All patients received VDC/IE (median 14 cycles.) Local therapy was surgery for 33, radiation therapy for 17, or both for 17. Median follow-up for living patients was 5.2 years. Six patients had disease progression on therapy. Site of first failure was local for three, local and distant for two, and distant for ten. Five-year LRFS was 91%; 5-year LRFS was 96% for nonpelvic disease and 64% for pelvic disease (p = .003). Five-year PFS was 66%, and 5-year OS was 79%. On multivariate analysis, pelvic site had a 3.3 times increased risk of progression (p = .01). CONCLUSION: Survival for adults with localized ES treated with VDC/IE-based multimodality therapy appears to be better than historical data and similar to excellent outcomes in children. Pelvic site of disease remains a predictor of worse outcome. Given the paucity of literature for adult ES, these data help validate VDC/IE-based therapy as an appropriate treatment approach for this rare disease in adults. IMPLICATIONS FOR PRACTICE: Ewing sarcoma (ES) is rare in adults. Treatment approaches for adults have been extrapolated from the pediatric experience, and there is a sense that adults fare less well than children. We reviewed treatment outcomes in adults with localized ES treated with cyclophosphamide, doxorubicin, and vincristine in alternation with ifosfamide and etoposide (VDC/IE) as part of multimodality therapy. Survival outcomes appear to be better than historical data for adults and similar to the excellent outcomes for children. These data help validate VDC/IE-based therapy as an appropriate treatment approach for this rare disease in adults.

Surveillance Imaging Patterns and Outcomes Following Radiation Therapy and Radical Resection for Localized Extremity and Trunk Soft Tissue Sarcoma.

BACKGROUND: Optimal surveillance imaging (SI) regimens following radiation therapy (RT) and radical resection for localized soft tissue sarcoma (STS) are unknown and practice patterns vary. METHODS: Between 2006 and 2014, 94 patients with localized STS of the extremity/trunk treated with preoperative RT and radical resection were identified. Timing of local recurrence (LR), distant recurrence (DR), and SI were evaluated. The Kaplan-Meier method was used to determine recurrence-free and overall survival (OS), and the method of recurrence detection (SI or due to signs/symptoms) was determined. RESULTS: Median tumor size was 7.5 cm, and 92% were intermediate/high grade. After a median follow-up of 60 months for surviving patients, 30 patients (32%) recurred, including 5 LRs and 26 DRs. The median time to LR and DR was 36.2 months (range 14.4-65.7) and 10.4 months (range 5.2-76.9), respectively, and the 5-year local recurrence-free survival (RFS), distant RFS, and OS was 95, 71, and 76%, respectively. Local SI was performed for 90% of patients, mostly by magnetic resonance imaging (MRI; 91%). Of the five LRs, two were detected by SI and three had signs/symptoms preceding imaging. All patients underwent distant SI. Of the 26 DRs, 23 (88%) were in the lung. SI detected 22 (85%) DRs, and only 4 of 26 had signs/symptoms prompting imaging. CONCLUSION: Given excellent local control with RT and radical resection for intermediate/high-grade STS of the extremity/trunk, SI of the primary site should be reserved for select patients at high risk of LR. Conversely, due to frequent occurrence of asymptomatic DR in the lungs, periodic lung SI is appropriate. Routine abdominopelvic SI may not be indicated for most histologies.

Cost-Effectiveness of Surveillance for Distant Recurrence in Extremity Soft Tissue Sarcoma.

BACKGROUND: Optimal distant recurrence (DR) surveillance strategies for extremity soft tissue sarcoma (STS) are unknown. We performed a cost-effectiveness analysis of different imaging modalities performed at guideline-specified intervals. METHODS: We developed a Markov model simulating lifetime outcomes for 54-year-old patients after definitive treatment for American Joint Committee on Cancer stage II-III extremity STS using four surveillance strategies: watchful waiting (WW), chest X-ray (CXR), chest computed tomography (CCT), and positron emission tomography-computed tomography (PET/CT). Probabilities, utilities, and costs were extracted from the literature and Medicare claims to determine incremental cost-effectiveness ratios (ICER). RESULTS: CCT was the most effective and most costly strategy with CXR the most cost-effective strategy at a societal willing-to-pay (WTP) of $100,000/quality-adjusted life year (QALY). The ICER was $12,113/QALY for CXR versus $104,366/QALY for CCT while PET/CT was never cost-effective. Sensitivity analyses demonstrated CCT becomes the preferred imaging modality as the lifetime risk of DR increases beyond 33% or as the WTP increases beyond $120,000/QALY. CONCLUSIONS: Optimal DR surveillance imaging for stage II-III extremity STS should be individualized based on patients' risks for DR. These results suggest CXR, or CCT performed at more protracted intervals, may be preferred for lower-risk patients (i.e., DR risk <33%), whereas CCT may be preferred for higher-risk patients (i.e., DR risk >33%). Further study of optimal strategies is needed. In the interim, these findings may help to refine guidelines to reduce resource overutilization during routine surveillance of lower-risk sarcoma patients.

Radiation Therapy for Soft-Tissue Sarcomas: A Primer for Radiologists.

Radiation therapy (RT) plays an important role in multimodality therapy for soft-tissue sarcomas (STS). RT treatment paradigms have evolved significantly in recent years, and many different complex RT modalities are commonly used in STS. These include external-beam RT, intensity-modulated RT, stereotactic body RT, and brachytherapy. Imaging is essential throughout the treatment process. Plain radiographs, computed tomography (CT), magnetic resonance imaging, ultrasonography, and positron emission tomography/CT all play potential roles in the management of STS. Before RT, high-quality imaging is needed to direct management decisions, both by global tumor staging and detailed assessment of the extent of local disease. At the time of RT, precise planning imaging is required to delineate tumor volumes, including gross tumor volume, clinical target volume, and planning target volume, which are used to direct therapy. In addition, imaging at the time of RT must outline the location of adjacent vital organs, to optimize treatment efficacy and minimize toxicity. After RT, imaging is needed to assess the patient for tumor response to therapy. In addition, imaging at regular intervals is often required to monitor for recurrence of disease and potential complications of therapy. The purpose of this review is to familiarize radiologists with the indications for RT in STS, common therapeutic modalities used, roles of imaging throughout the treatment process, and complications of therapy.

Role of Imaging in Management of Desmoid-type Fibromatosis: A Primer for Radiologists.

Desmoid-type fibromatosis (DF) is a locally aggressive fibroblastic neoplasm that has variable clinical and biologic behaviors ranging from indolent tumors that can undergo spontaneous regression to aggressive tumors with a tendency toward local invasion and recurrence. The management of DF has evolved considerably in the last decade from aggressive first-line surgery and radiation therapy to systemic treatment (chemotherapy, hormonal therapy, and targeted therapy) and symptomatic local control (surgery and radiation therapy). Imaging plays an important role in each of these treatment settings. In surgical candidates, computed tomography (CT) and magnetic resonance (MR) imaging are the modalities of choice for assessing resectability and surgical planning. For evaluating recurrence, MR imaging is the modality of choice for extra-abdominal recurrence, whereas CT is the preferred modality for intra-abdominal recurrence. Signal intensity changes at MR imaging can be used to monitor the biologic behavior of certain DFs chosen for expectant management. Response to systemic treatment with anti-inflammatory agents, hormonal therapy (eg, tamoxifen), cytotoxic chemotherapy (eg, doxorubicin, vinblastine, methotrexate), and targeted therapy (eg, sorafenib), as well as to radiation therapy, can be assessed at CT by monitoring size and attenuation changes or at MR imaging by monitoring size, T2 signal intensity, and degree of enhancement. Several patterns of response can be seen at imaging. Imaging also helps in detecting complications associated with systemic therapy and radiation therapy. (©)RSNA, 2016.

Does CT-based Rigidity Analysis Influence Clinical Decision-making in Simulations of Metastatic Bone Disease?

BACKGROUND: There is a need to improve the prediction of fracture risk for patients with metastatic bone disease. CT-based rigidity analysis (CTRA) is a sensitive and specific method, yet its influence on clinical decision-making has never been quantified. QUESTIONS/PURPOSES: What is the influence of CTRA on providers' perceived risk of fracture? (2) What is the influence of CTRA on providers' treatment recommendations in simulated clinical scenarios of metastatic bone disease of the femur? (3) Does CTRA improve interobserver agreement regarding treatment recommendations? METHODS: We conducted a survey among 80 academic physicians (orthopaedic oncologists, musculoskeletal radiologists, and radiation oncologists) using simulated vignettes of femoral lesions presented as three separate scenarios: (1) no CTRA input (baseline); (2) CTRA input suggesting increased risk of fracture (CTRA+); and (3) CTRA input suggesting decreased risk of fracture (CTRA-). Participants were asked to rate the patient's risk of fracture on a scale of 0% to 100% and to provide a treatment recommendation. Overall response rate was 62.5% (50 of 80). RESULTS: When CTRA suggested an increased risk of fracture, physicians perceived the fracture risk to be slightly greater (37% ± 3% versus 42% ± 3%, p < 0.001; mean difference [95% confidence interval {CI}] = 5% [4.7%-5.2%]) and were more prone to recommend surgical stabilization (46% ± 9% versus 54% ± 9%, p < 0.001; mean difference [95% CI] = 9% [7.9-10.1]). When CTRA suggested a decreased risk of fracture, physicians perceived the risk to be slightly decreased (37% ± 25% versus 35% ± 25%, p = 0.04; mean difference [95% CI] = 2% [2.74%-2.26%]) and were less prone to recommend surgical stabilization (46% ± 9% versus 42% ± 9%, p < 0.03; mean difference [95% CI] = 4% [3.9-5.1]). The effect size of the influence of CTRA on physicians' perception of fracture risk and treatment planning varied with lesion severity and specialty of the responders. CTRA did not increase interobserver agreement regarding treatment recommendations when compared with the baseline scenario (κ = 0.41 versus κ = 0.43, respectively). CONCLUSIONS: Based on this survey study, CTRA had a small influence on perceived fracture risk and treatment recommendations and did not increase interobserver agreement. Further work is required to properly introduce this technique to physicians involved in the care of patients with metastatic lesions. Given the number of preclinical and clinical studies outlining the efficacy of this technique, better education through presentations at seminars/webinars and symposia will be the first step. This should be followed by clinical trials to establish CTRA-based clinical guidelines based on evidence-based medicine. Increased exposure of clinicians to CTRA, including its underlying methodology to study bone structural characteristics, may establish CTRA as a uniform guideline to assess fracture risk. LEVEL OF EVIDENCE: Level III, economic and decision analyses.