Oncological outcome after hyperthermic isolated limb perfusion for primarily unresectable versus locally recurrent soft tissue sarcoma of extremities

IntroductionThe management of locally advanced extremity soft tissue sarcomas, particularly in terms of a limb salvage strategy, represents a challenge, especially in recurrent tumors. In the context of a patient-tailored multimodal therapy, hyperthermic isolated limb perfusion (ILP) is a promising limb-saving treatment option. We report the outcome of patients with primarily irresectable and locally recurrent soft tissue sarcoma (STS) treated by ILP.Patients and methodsData about patient demographics, clinical und histopathological characteristics, tumor response, morbidity and oncological outcome of all patients with STS, who underwent an ILP at our institution in a 10-year period, were retrospectively detected and analyzed.ResultsThe cohort comprised 30 patients. Two patients were treated with ILP for palliative tumor control, 13 patients because of a local recurrent soft tissue sarcoma (rSTS) and 15 patients because of primarily unresectable soft tissue sarcoma (puSTS). 25 of the 28 patients with curative intention received surgery after ILP (11 pts with rSTS and 14 pts with puSTS). Histopathologically we observed complete response in 6 patients (24%) and partial responses in 19 patients (76%) with a significant better remission in patients with puSTS (p = 0,043). Limb salvage rate was 75%. Mean follow-up was 69 months [range 13–142 months]. Seven (7/11; 64%) patients with rSTS and one (1/14; 7%) patient with puSTS developed local recurrence after ILP and surgery, whereas eight (8/13; 62%) rSTS patients and seven (7/15; 47%) puSTS patients developed distant metastasis. During follow-up, eight patients (28.5%) died of disease (5/13; 38%) rSTS and 3/15 (20%) puSTS. ILP in the group of previously irradiated sarcoma patients (n = 13) resulted in a limb salvage rate of 69% and was not associated in an increased risk for adverse events.DiscussionILP for advanced extremity STS is a treatment option for both puSTS and rSTS resulting in good local control and should be considered in multimodal management. ILP is also a good option for patients after radiation history.     

Phase IB study of the combination of docetaxel,gemcitabine, and bevacizumab in patients with advanced or recurrent soft tissue sarcoma: the Axtell regimen

BackgroundTo assess the response of patients with soft tissue sarcoma (STS) to the combination of docetaxel, bevacizumab, and gemcitabine. Vascular endothelial growth factor (VEGF)-A levels and expression of VEGF-A and VEGF receptors 1 and 2 were evaluated.Patients and methodsThirty-eight chemotherapy-naive patients with STS were enrolled. A dose-finding study for gemcitabine from 1000, 1250, then 1500 mg/m² was done in nine patients (three cohorts), followed by an expansion cohort of 27 patients. Dose of docetaxel was 50 mg/m², bevacizumab was 5 mg/kg, and gemcitabine was 1500 mg/m², every 2 weeks. Serum VEGF-A was measured by enzyme-linked immunosorbent assay and tissue VEGF-A and its receptors by immunohistochemistry.ResultsThe median follow-up was 36 months. The overall response rate observed was 31.4%, with 5 complete and 6 partial responses, and 18 stable diseases lasting for a median of 6 months. There was no significant hematologic toxicity. The adverse events with the highest grade were attributed to bevacizumab. There was no correlation of VEGF pathway biomarkers with outcome.ConclusionsThe combination of gemcitabine, docetaxel, and bevacizumab is safe and effective in patients with STS. The most concerning adverse events were consequences of bevacizumab administration. The benefit of bevacizumab in this patient population remains unclear.     

Treatment challenges in and outside a network setting: Soft tissue sarcomas

Patients with soft tissue sarcoma (STS) experienced better outcomes when treated according to existing clinical practice guidelines either at reference institution or dedicated treatment networks. Despite increasing evidence supporting referral to sarcoma specialised units, up to half of patients are not managed according to guidelines, particularly those in the early stage of their disease requiring surgery. Also, criteria to certify expertise of institutions, such as the treatment volume, are debated and health authorities have only recently started identification of these centres and creation of treatment networks in Europe as well as in several countries. This process have important implications for both patient outcomes and innovation of existing treatment strategies through clinical research, making improvement of clinical pathways a priority for health care authorities. This article will discuss issues with management of patients with STS, such as pathological diagnosis and adherence to guidelines, and the definition of referral centres and networks will be illustrated along with existing experiences and population-based data.     

Outcome of chemotherapy in advanced synovial sarcoma patients: Review of 15 clinical trials from the European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group; setting a new landmark for studies in this entity

IntroductionPrevious studies in metastatic soft tissue sarcomas (STS) showed that synovial sarcomas tend to have better survival rates and a higher chemosensitivity than other STS subtypes. However, data are derived from relatively small subgroups and statistical significance of these observations is lacking. Larger cohorts are necessary to define and confirm the specific characteristics of this subtype.Patients and methodsPatient data were retrieved from 15 European Organisation for Research and Treatment of Cancer advanced first-line STS trials. Patient characteristics, survival and treatment response of synovial sarcoma patients were compared to other STS patients. Univariable and multivariable analyses were performed to evaluate prognostic factors.ResultsIn total, 3330 advanced STS patients were retrieved, of whom 313 had a synovial sarcoma. Synovial sarcoma patients were significantly younger (median 40 versus 52 years), more often had extremity primary tumours and had a better performance status (PS 0: 50.2 versus 43.4%) compared to other STS patients. Additionally, synovial sarcoma patients had a significantly better response to chemotherapy (responders: 27.8 versus 18.8%) and better survival rates (progression free survival [PFS]: 6.3 versus 3.7 months; Overall survival [OS]: 15.0 versus 11.7 months). Age, PS, and presence of metastatic disease were defined as prognostic factors for PFS and OS in the univariable analysis. The last two factors were confirmed in the multivariable analysis for OS.DiscussionAdvanced synovial sarcomas are a distinct subgroup of STS, with a better response to systemic chemotherapy and longer PFS and OS. These results should be taken into account in the design of future synovial sarcoma specific studies.     

Doxorubicin-based adjuvant chemotherapy in soft tissue sarcoma: pooled analysis of two STBSG-EORTC phase III clinical trials

BackgroundThe EORTC-STBSG coordinated two large trials of adjuvant chemotherapy (CT) in localized high-grade soft tissue sarcoma (STS). Both studies failed to demonstrate any benefit on overall survival (OS). The aim of the analysis of these two trials was to identify subgroups of patients who may benefit from adjuvant CT.Patients and methodsIndividual patient data from two EORTC trials comparing doxorubicin-based CT to observation only in completely resected STS (large resection, R0/marginal resection, R1) were pooled. Prognostic factors were assessed by univariate and multivariate analyses. Patient outcomes were subsequently compared between the two groups of patients according to each analyzed factor.ResultsA total of 819 patients had been enrolled with a median follow-up of 8.2 years. Tumor size, high histological grade and R1 resection emerged as independent adverse prognostic factors for relapse-free survival (RFS) and OS. Adjuvant CT is an independent favorable prognostic factor for RFS but not for OS. A significant interaction between benefit of adjuvant CT and age, gender and R1 resection was observed for RFS and OS. Males and patients >40 years had a significantly better RFS in the treatment arms, while adjuvant CT was associated with a marginally worse OS in females and patients <40years. Patients with R1 resection had a significantly better RFS and OS favoring adjuvant CT arms.ConclusionAdjuvant CT is not associated with a better OS in young patients or in any pathology subgroup. Poor quality of initial surgery is the most important prognostic and predictive factor for utility of adjuvant CT in STS. Based on these data, we conclude that adjuvant CT for STS remains an investigational procedure and is not a routine standard of care.     

UK guidelines for the management of soft tissue sarcomas

Soft tissue sarcomas (STS) are rare tumours arising in mesenchymal tissues, and can occur almost anywhere in the body. Their rarity, and the heterogeneity of subtype and location means that developing evidence-based guidelines is complicated by the limitations of the data available. However, this makes it more important that STS are managed by teams, expert in such cases, to ensure consistent and optimal treatment, as well as recruitment to clinical trials, and the ongoing accumulation of further data and knowledge. The development of appropriate guidance, by an experienced panel referring to the evidence available, is therefore a useful foundation on which to build progress in the field. These guidelines are an update of the previous version published in 2010 (Grimer et al. in Sarcoma 2010:506182, 2010). The original guidelines were drawn up following a consensus meeting of UK sarcoma specialists convened under the auspices of the British Sarcoma Group (BSG) and were intended to provide a framework for the multidisciplinary care of patients with soft tissue sarcomas. This current version has been updated and amended with reference to other European and US guidance. There are specific recommendations for the management of selected subtypes of disease including retroperitoneal and uterine sarcomas, as well as aggressive fibromatosis (desmoid tumours) and other borderline tumours commonly managed by sarcoma services. An important aim in sarcoma management is early diagnosis and prompt referral. In the UK, any patient with a suspected soft tissue sarcoma should be referred to one of the specialist regional soft tissues sarcoma services, to be managed by a specialist sarcoma multidisciplinary team. Once the diagnosis has been confirmed using appropriate imaging, plus a biopsy, the main modality of management is usually surgical excision performed by a specialist surgeon. In tumours at higher risk of recurrence or metastasis pre- or post-operative radiotherapy should be considered. Systemic anti-cancer therapy (SACT) may be utilized in some cases where the histological subtype is considered more sensitive to systemic treatment. Regular follow-up is recommended to assess local control, development of metastatic disease, and any late-effects of treatment. For local recurrence, and more rarely in selected cases of metastatic disease, surgical resection would be considered. Treatment for metastases may include radiotherapy, or systemic therapy guided by the sarcoma subtype. In some cases, symptom control and palliative care support alone will be appropriate.     

Significance of intraoperative radiation therapy and high cumulative radiation doses in retroperitoneal soft tissue sarcoma

IntroductionIn retroperitoneal soft tissue sarcoma (STS) local recurrence (LR) rates remain high despite more aggressive surgical approaches. Since wide resection margins cannot be achieved in all patients, application of intraoperative radiation therapy (IORT) has been frequently discussed. Still, the significance of IORT in multimodal treatment of retroperitoneal STS remains unclear.Material and methodsPatients undergoing resection of primary or recurrent retroperitoneal STS at the University of Heidelberg Department of General, Visceral and Transplantation Surgery were retrospectively analyzed. Univariate Kaplan-Meyer and multivariate Cox regression analyses were performed to identify predictors of LR-free survival and to investigate the impact of IORT and high cumulative radiation doses. Analyses with propensity-score matched subgroups for IORT and cumulative radiation dose were performed to control for selection bias. Subgroup analyses for patients with retroperitoneal liposarcoma were likewise performed.Results272 patients were identified. Recurrent tumors, histology of dedifferentiated liposarcoma or unclassified sarcoma and microscopically incomplete resection were associated with decreased LR-free survival. In liposarcoma, only recurrent and dedifferentiated tumors were confirmed as poor prognostic factors concerning LR. IORT and cumulative radiation doses exceeding 60 Gy did not influence LR rates (estimated 5-year LR-free survival: IORT: 39%, non-IORT: 46%; p = 0.79).ConclusionIn this retrospective evaluation, additional application of IORT does not significantly influence oncological outcome in retroperitoneal soft tissue sarcoma. Randomized trials are needed to clarify the benefit of IORT.     

Unplanned excision of soft tissue sarcoma: The impact of the referring hospital

Background: Unplanned excision of soft tissue sarcoma (STS) remains a common problem performed at various levels of hospitals, where clinical characteristics may differ. However, there is little literature describing the impact of the referring hospital on patient characteristics and/or outcome in unplanned excision of STS. This study examined the possible different patient characteristics and prognoses according to the level of referring hospitals where unplanned excision was performed.Methods: Patients referred to our institute after unplanned excision of STS on their extremities were reviewed. Referring hospitals were categorized into two groups according to their referral grades; tertiary hospitals (general hospitals with tertiary [highest] referral grade, n = 42) and non-tertiary hospitals (others, n = 79).Results: Patients referred from tertiary hospitals had significantly larger number of high-grade tumors (p = 0.019) but lower chance of finding a residual tumor at re-excision (p = 0.020) than non-tertiary hospitals. For oncological outcomes, referral from tertiary hospital was an independent factor for better local control (hazard ratio, 0.211; 95% confidence interval, 0.061–0.730). However, there was no difference in disease-specific death (p = 0.729) or metastasis (p = 0.978) between the two groups.Conclusions: Despite having worse clinicopathologic characteristics, patients referred from tertiary hospitals had fewer local recurrences than patients from non-tertiary hospitals. The impact of the referring hospital on patient outcome and disease characteristics needs to be considered in unplanned excision of STS.     

The prognostic role of the preoperative systemic immune-inflammation index and high-sensitivity modified Glasgow prognostic score in patients after radical operation for soft tissue sarcoma

IntroductionThe prognostic values of nutritional and immune-inflammatory indicators in non-metastatic soft tissue sarcoma (STS) patients are not clear. We investigated the utility of systemic immune-inflammation index (SII) and the high-sensitivity modified Glasgow prognostic score (Hs-mGPS) in the prediction of STS patient's prognosis.Materials and methodsPatients admitted between January 2000 and December 2016, who underwent R0 resection for STS at SYSUCC were carefully retrospectively reviewed, and 454 patients were enrolled. The laboratory data and clinical data were collected from the patient's record. ROC analysis is used to determine the optimal cutoff value. Survival curves were analysed by Kaplan-Meier method. Cox proportional hazard model was used to find out prognostic variables.ResultsIncreased SII and Hs-mGPS values were significantly related to larger tumour size, deep tumour location, higher tumour grade and more advanced American Joint Committee on Cancer (AJCC) stage. Patients with an elevated SII had a shorter median survival time and a lower 5-year OS rate than those with a low SII. And patients with low Hs-mGPS had longer median OS and DFS. Multivariate analysis revealed that both the SII and the Hs-mGPS were independent predictive indicators for OS. And a joint model containing both the Hsm-GPS and the SII appeared to have the strongest predictive ability.ConclusionOur findings indicated that malnutrition and systemic inflammation are risk factors for the survival of STS patients after operation, and early recognition and intervention of malnutrition and systemic inflammation may help to improve the survival of the patients.     

Effective follow-up strategies in soft tissue sarcoma.

The value of surveillance for detection of recurrences in patients with soft tissue sarcoma (STS) after definitive surgical resection of the primary tumor is based on the premise that early recognition and treatment of local or distant recurrence can prolong survival. Surveillance strategies should meet the criteria of easy implementation, accuracy, and cost-effectiveness. Although guidelines have been proposed for follow-up of patients with STS, there are few data in the medical literature on the effectiveness of these recommendations. We reviewed the effectiveness of a surveillance program for primary extremity STS in an effort to provide an evidence-based rationale for follow-up of STS. We concluded that clinical assessment of patient symptoms, chest X-ray imaging, and physical examination are effective strategies for follow-up of extremity STS. Chest X-ray imaging also appears to be cost-effective, at least for high-grade extremity STS. Imaging of the primary extremity site by computed tomography (CT) scan or magnetic resonance imaging (MRI) on an annual basis and routine laboratory blood tests were ineffective strategies for recurrence detection. However, certain patient characteristics such as body habitus, previous radiation therapy, and location of the primary tumor site may require the use of CT scans and MRI for adequate clinical assessment. The role of specific surveillance strategies for recurrence detection for sarcomas of the trunk, head and neck, retroperitoneum, and viscera has yet to be defined.     

Dosimetric Comparison of Volumetric Modulated Arc Therapy and Intensity Modulated Radiation Therapy for Soft Tissue Sarcoma of the Extremities

PurposeRadiation therapy is a standard part of limb conserving therapy for extremity soft tissue sarcoma (STS) at high risk of recurrence. Toxic effects increase with radiation dose and volume of normal tissue irradiated. This study sought to compare dosimetry of volumetric modulated arc therapy (VMAT) with intensity modulated radiation therapy (IMRT) and to investigate the optimal planning technique.Methods and MaterialsTwenty patients with extremity STS who underwent preoperative radiation therapy (50 Gy in 25 fractions) between 2016 and 2020 at a specialised sarcoma center were included. The original treatment techniques were sliding window IMRT or 3-dimensional conformal. VMAT plans were retrospectively generated according to the original tumor and organ-at-risk constraints. Quality assurance was performed as per departmental protocol. Wilcoxon signed-rank test was used to compare dosimetric parameters (for planning target volume [PTV], in-field bone, and soft tissue structures), monitor units (MUs), and treatment time.ResultsMedian patient age was 65 years and the majority were male (n = 14, 70%). The most common subtype was undifferentiated pleomorphic sarcoma (n = 14, 70%), and most tumors were located on the thigh (n = 12, 60%). Median PTV was 1110 cm³ and median volume of in-field bone 236 cm³. VMAT plans had significantly lower average MU (480 vs 862 MU, P < .001) and overall treatment time (300 vs 153 seconds, P < .001). PTV coverage favored VMAT, with marginally higher mean, minimum, and maximum doses and higher conformity index. However, differences were not statistically significant. Dose to infield bone and soft tissue structures were similar or slightly lower with VMAT.ConclusionsIn extremity STS, VMAT plans demonstrated a favorable trend toward tumor coverage and dose conformity compared with IMRT along with significantly lower MUs and half the overall treatment time.     

Prognostic and predictive factors for outcome to first-line ifosfamide-containing chemotherapy for adult patients with advanced soft tissue sarcomas: An exploratory,retrospective analysis on large series from the European Organization for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group (EORTC-STBSG)

BackgroundAdult patients with advanced soft tissue sarcomas (STS) are generally treated similarly, regardless of great differences between STS subtypes, disease presentation and patients’ characteristics. As ifosfamide is frequently applied in first line systemic therapy, we aimed to establish prognostic and predictive factors for outcome to ifosfamide-based therapy.MethodsA retrospective, exploratory analysis was performed on data from 1337 advanced STS patients who received first-line ifosfamide-containing chemotherapy. For predictive factor analysis, 660 patients treated with doxorubicin monotherapy served as comparators.ResultsIndependent favourable prognostic factors for overall survival (OS) were good performance status, female gender, low histological grade, extremity primary tumour site and locally advanced disease; for progression-free survival (PFS), the combination of doxorubicin and ifosfamide, locally advanced disease, and tumour entity with a lower risk to progress for synovial sarcoma patients compared to leiomyosarcoma. For response, independent favourable prognostic factors were doxorubicin combined with ifosfamide, higher histological grade, and histology with synovial sarcoma patients having the highest chance to respond. Predictive factor analysis showed that compared to doxorubicin monotherapy, patients who benefited less from ifosfamide-based therapies were leiomyosarcoma patients in terms of OS, and patients with liposarcoma for response. No predictive factors were found for PFS.ConclusionIn this study, we established an independent set of prognostic and predictive factors for outcome to ifosfamide-based chemotherapy in advanced STS patients. This study provides important information for the interpretation and design of clinical trials for specific STS entities and may contribute to further treatment individualisation of advanced STS patients.     

First-line anthracycline-based chemotherapy for angiosarcoma and other soft tissue sarcoma subtypes: Pooled analysis of eleven European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group trials

BackgroundAngiosarcoma is a rare subtype of soft tissue sarcoma (STS). Doxorubicin is the standard first-line chemotherapy for advanced STS. It is not known whether angiosarcoma response to anthracycline-based chemotherapy is different to other STS subtypes.MethodsPooled data were analysed from 11 prospective randomised and non-randomised European Organisation for Research and Treatment of Cancer (EORTC) clinical trials of first-line anthracycline-based chemotherapy for advanced STS. Baseline patient characteristics, chemotherapy response, progression free survival (PFS) and overall survival (OS) of angiosarcoma patients were compared with other STS patients. Analysis was performed to identify factors prognostic for angiosarcoma response to chemotherapy, PFS and OS.ResultsWith a median follow-up of 4.2 years, data from 108 locally advanced and metastatic angiosarcoma patients and 2557 patients with other STS histologies were analysed. 25% of angiosarcoma patients had a complete or partial response to chemotherapy compared to 21% for other STS histotypes. The median PFS was 4.9 months and OS 9.9 months, which were not significantly different from other STS histotypes. In univariate analysis, bone metastases were an adverse prognostic factor for OS (hazard ratio (HR) 1.66, 95% confidence interval (CI) 1.03–2.67; p = 0.036). Tumour grade was as an adverse prognostic factor for PFS (HR 1.72, 95% CI 1.01–2.92; p = 0.044) and OS (HR 2.03; 95% CI 1.16–3.56; p = 0.011). Compared to single agent anthracyclines, doxorubicin + ifosfamide was associated with improved PFS (HR 0.53, 95% CI 0.33–0.86; p = 0.010) and OS (HR 0.53, 95% CI 0.32–0.90; p = 0.018).ConclusionsAngiosarcoma response and survival following first-line anthracycline-based chemotherapy was similar to other STS histotypes. Our analysis provides a useful measure of angiosarcoma response to chemotherapy for comparison with future clinical trials.     

Neoadjuvant radiation influences the pseudocapsule in soft tissue sarcoma: A histopathologic and radiographic evaluation

Background and objectivesA pseudocapsule surrounds soft tissue sarcoma (STS). Its composition, response to neoadjuvant radiation, and clinical significance are poorly understood.MethodsSeventeen cases of high-grade undifferentiated pleomorphic sarcoma (UPS) were reviewed, ten of which were treated with neoadjuvant radiation. Magnetic resonance imaging (MRI) studies, pathology slides, and patient records were reviewed.ResultsIrradiated pseudocapsules were well-demarcated with fewer viable tumor cells and were thicker on both pathology and MRI measurements when compared to non-irradiated pseudocapsules (p < 0.001, p = 0.04, respectively). Pseudocapsule mean pathology width (MPW) was positively correlated with tumor necrosis percentage (p = 0.044), and negatively correlated with mitotic rate (p = 0.043), though pseudocapsule width measured on MRI did not correlate with these prognostic factors. Despite an evident treatment response to neoadjuvant radiation, viable tumor cells were present within the pseudocapsule and the surrounding healthy tissue.ConclusionsThe pseudocapsule in STS responds to radiation and there appears to be a correlation between pseudocapsule width and tumor necrosis and mitotic activity. As viable tumor cells are present beyond the pseudocapsule, surgeons should remain cautious in determining margins of resection in STS when using the pseudocapsule as a palpable landmark. This novel study is the most detailed to date to describe the histopathologic and radiographic characteristics of the STS pseudocapsule. Further studies are needed to determine the clinical significance of the pseudocapsule.     

Radiation Therapy for Treatment of Soft Tissue Sarcoma in Adults: Executive Summary of an ASTRO Clinical Practice Guideline

PurposeThis guideline provides evidence-based recommendations addressing the indications for radiation therapy (RT), sequencing of local therapies, and appropriate dose and planning techniques for management of primary, operable, localized, soft tissue sarcoma (STS) in adults.MethodsThe American Society for Radiation Oncology convened a task force to address 5 key questions focused on the use of RT for management of STS. These questions included indications for RT for STS of the extremity and superficial trunk; considerations for sequencing of RT with respect to surgery, dose of RT, appropriate treatment volumes and techniques; and the role of RT in management of retroperitoneal sarcoma. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and system for grading evidence quality and recommendation strength.ResultsMultidisciplinary evaluation and decision making are recommended for all cases of STS. RT is recommended for patients in whom there is increased risk of local recurrence of resected STS, particularly if close or microscopically positive margins are anticipated or have occurred. When RT is indicated, preoperative RT is strongly recommended over postoperative RT. Postoperative RT is conditionally recommended in specific clinical circumstances (eg, uncontrolled pain or bleeding) or when the risk of wound complications outweighs that of late toxicity from RT. Routine use of RT in addition to oncologic resection for retroperitoneal sarcoma is conditionally not recommended. When RT is used for retroperitoneal sarcoma, preoperative RT is recommended, whereas postoperative RT is not recommended.ConclusionsBased on currently published data, the American Society for Radiation Oncology task force has proposed evidence-based recommendations regarding the use of RT for STS in adults. Future studies will ascertain whether alterations in dosing and sequencing may optimize outcomes and quality of life.     

First-line chemotherapy for malignant peripheral nerve sheath tumor (MPNST) versus other histological soft tissue sarcoma subtypes and as a prognostic factor for MPNST: an EORTC Soft Tissue and Bone Sarcoma Group study

Background: The role of chemotherapy in advanced malignant peripheral nerve sheath tumor (MPNST) is unclear.Patients and methods: Chemotherapy-naive soft tissue sarcomas (STS) patients treated on 12 pooled nonrandomized and randomized European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group trials were retrospectively analyzed. Clinical outcomes, overall survival, progression-free survival (PFS) and response were determined for MPNST and other STS histotypes and compared. Additionally, prognostic factors within the MPNST population were defined. Studied cofactors were demographics, sarcoma history, disease extent and chemotherapy regimen.Results: After a median follow-up of 4.1 years, 175 MPNST out of 2675 eligible STS patients were analyzed. Outcome was similar for MPNST versus other STS histotypes, with a response rate, median PFS and overall survival of 21% versus 22%, 17 versus 16 weeks and 48 versus 51 weeks, respectively. Performance status was an independent prognostic factor for overall survival. Chemotherapy regimen was an independent prognostic factor for response (P < 0.0001) and PFS (P = 0.009). Compared with standard first-line doxorubicin, the doxorubicin–ifosfamide regimen had the best response, whereas ifosfamide had the worst prognosis.Conclusion: This series indicates the role of chemotherapy in treatment of advanced MPNST. This first comparison showed similar outcomes for MPNST and other STS histotypes. The apparent superiority of the doxorubicin–ifosfamide regimen justifies further investigations of this combination in randomized trials.     

International expert opinion on patient-tailored management of soft tissue sarcomas

BackgroundSoft tissue sarcomas (STS) are a heterogeneous group of cancers comprising over 50 histological subtypes. Current treatment strategies for sarcomas are increasingly adapted to histological and molecular subtype, and several patient- and tumour-related factors influence treatment decision.MethodsSeven oncologists specialising in the management of STS, from Europe, the United States of America and Japan, met to develop a practical model to identify parameters guiding treatment decision-making in advanced STS. Literature searches were carried out to identify key published evidence, in particular phase II and III randomised trials, to validate the model, and extensive clinical experience was used as expert evidence. A document was developed to provide a logical approach to advanced STS management and was analysed critically by a second group of STS specialists.ResultsBroad consensus was reached during this exercise and the following parameters were identified as key factors influencing treatment decision: chemosensitivity of histological subtype, natural history of the diagnosis, tumour burden, tumour site, locally advanced primary and/or metastases, patient’s general condition, relevant comorbidities, previous chemotherapy, treatment goal and patient acceptance. These parameters, judged useful for treatment selection, were based on published literature, the selection process within clinical trials and expert opinion (some factors have not been formerly defined in published literature).ConclusionA model describing factors affecting treatment decisions in sarcoma was established. The model requires validation and several of its parameters require standardisation.     

Olaratumab for the treatment of advanced soft tissue sarcoma

Introduction: Olaratumab, a human monoclonal antibody against platelet derived growth factor receptor alpha (PDGFR- α), is the first drug that in combination with doxorubicin for the treatment of patients with advanced/metastatic soft tissue sarcoma (STS) that has showed an improved overall survival compared to doxorubicin alone. These initial results are exciting and have the potential to change the landscape of treatment for patients with STS.

Areas covered: This article reviews the development of olaratumab for oncology use by reviewing articles in PubMed for ‘platelet derived growth factor’ and ‘receptor’ and ‘soft tissue sarcoma’. We provide an overview of the published studies to date for olaratumab and specifically the use in soft tissue sarcoma.

Expert commentary: Olaratumab is a well-tolerated drug that, when combined with doxorubicin, has shown an improved overall survival compared to doxorubicin alone and the phase III confirmatory study is eagerly awaited.     

Quality of life measures in soft tissue sarcoma

The assessment of health-related quality of life (HRQL) via patient-reported outcomes has the potential to answer critical questions and improve the care of soft tissue sarcoma (STS). This review outlines the rationale for quality of life measures in sarcoma, and details various instrument types: disease- and anatomic-specific, provider-generated, generic HRQL and health state utilities. Prior usage in STS populations, relative advantages of specific patient-reported outcome measures and a framework for selecting appropriate measures are discussed. Uniform incorporation of validated HRQL measures in STS clinical research would further the understanding of patient wellbeing beyond traditional clinical measures, and more widespread use of health state utilities measures in particular has the potential to facilitate comparative effectiveness research.