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.

Desmoid tumors: who, when and how to treat?

PURPOSE OF REVIEW: The objective of this article is to summarize new treatment strategies of desmoid tumors. RECENT FINDINGS: Desmoid tumor has an unpredictable evolution that may spontaneously regress or stabilize. A shift toward an initial frontline active surveillance has been acknowledged by experts. Surveillance monitoring should be performed frequently after the diagnosis to avoid missing a significant progression and then spaced in case of stabilization. Treatment is based on significant tumor growth or symptoms. Recent guidelines recommend commencing medical treatment. Kinase inhibitors and cytotoxic agents are the two classes of drugs where studies included progressive desmoid tumors and should be selected to guide medical practice. In a randomized trial, 2 years progression-free survival (PFS) was significantly better in the sorafenib group (81 versus 36% in the placebo group). In another randomized phase 2, 6 months PFS was 83.7% with pazopanib versus 45% with methotrexate and vinblastine. In a retrospective study, including progressive desmoid tumors, methotrexate + vinca alkaloids achieved 75 months median PFS. Cryotherapy is an alternative option in desmoid tumors with compatible locations and tumor sizes. Following medical treatment or cryotherapy failure, superficial sites represent the best indications for surgery in cases of continuous progression. In the event of a contra-indication or failure of medical treatment, in locations where surgery would be mutilating and incomplete, radiotherapy is an effective option. SUMMARY: Active surveillance with planned imaging has become the first-line management in desmoid tumor.

A phase II study on the neo-adjuvant combination of pazopanib and radiotherapy in patients with high-risk, localized soft tissue sarcoma.

PURPOSE: A prior phase I study showed that the neo-adjuvant combination of pazopanib and radiotherapy was well tolerated, and induced promising pathological responses in soft-tissue sarcoma patients. Results of the subsequent prospective, multicenter phase II, PASART-2 trial are presented here, further investigating the efficacy and safety of this combination. PATIENTS AND METHODS: Patients with high-risk, localized soft-tissue sarcoma received neo-adjuvant radiotherapy, 50 Gy in 25 fractions (PASART-2A) or with a subsequent dose de-escalation to 36 Gy in 18 fractions (PASART-2B). This was combined with 800 mg once daily pazopanib, which started one week before radiotherapy and finished simultaneously. After an interval of 4-8 weeks, surgical resection was performed. The primary endpoint was the rate of pathological complete responses (pCR), defined as ≤5% viable cells. RESULTS: 25 patients were registered in the study, 21 in PASART-2A and 4 in PASART-2B. After central pathology review, the combination treatment led to a pCR in 5 patients (20%). 17 patients (68%) experienced grade 3+ toxicities during neo-adjuvant treatment, of which the most common were alanine aminotransferase (ALT) elevation, aspartate aminotransferase (AST) elevation, and hypertension, all asymptomatic. Grade 3+ acute post-operative toxicities occurred in 5 patients (20%), of which the most common was wound infection. All patients completed the full radiotherapy regimen and underwent surgery. Pazopanib was discontinued before completion in 9 patients (36%), due to elevated ALT and/or AST, and shortly interrupted in 2 patients (8%), due to hypertension. CONCLUSION: Apart from asymptomatic hepatotoxicity, the study regimen was well tolerated. Although the pre-specified efficacy endpoint (30% pCR) was not met, a more than doubling of historical pCR rates after neo-adjuvant radiotherapy alone was observed, which warrants further investigation.

Outcome of Primary Desmoid Tumors at All Anatomic Locations Initially Managed with Active Surveillance.

BACKGROUND: The behavior of desmoid tumors is unpredictable and varies from spontaneous remission to symptomatic and radiologic progression. This study aimed to evaluate the radiologic and symptomatic course of the disease in patients initially managed with active surveillance. METHODS: Patients with a primary desmoid tumor at any anatomic location diagnosed between 1998 and 2016 were identified in a prospectively maintained database from a single sarcoma reference center in the United Kingdom. Inverse univariate Cox proportional hazard regression analyses were conducted to evaluate the course of the disease and indications for initiating treatment. RESULTS: The study identified 168 patients with a primary desmoid tumor initially managed with active surveillance. The tumors were located in the abdominal wall (n = 61, 36%), an extremity (n = 51, 30%), chest wall (n = 30, 18%), intra-abdominal site (n = 15, 9%), or elsewhere (n = 11, 6%). Of all the patients, 36% experienced radiologic progressive disease, 36% had stable disease, and 27% regressed. The patients younger than 50 years were more likely to progress (p = 0.046), whereas the patients with chest wall or upper-extremity tumors reported significantly more pain (p = 0.01). Eventually, 46% of the patients proceeded to treatment. The median time to start of treatment after initial surveillance was 31 months, whereas the median follow-up time for the patients not receiving any treatment was 40.5 months. The indications for initiation of treatment were pain (32%), progression (31%), or both (13%). CONCLUSIONS: Patients with desmoid tumors can be managed with initial active surveillance, although almost half of patients may eventually need treatment. Pain, tumor progression, or both are the most common indications for the initiation of treatment.

Dedifferentiated Liposarcoma: Updates on Morphology, Genetics, and Therapeutic Strategies.

Well-differentiated liposarcoma (WDL) and dedifferentiated liposarcoma (DDL) form the largest subgroup of liposarcomas, and represent a morphologic and behavioral spectrum of 1 disease entity, which arises typically in middle to late adult life, most frequently within the retroperitoneum or extremities. DDL is defined as nonlipogenic sarcoma that is juxtaposed to WDL, occurs as a recurrence of WDL or which can arise de novo, and typically has the appearance of undifferentiated pleomorphic or spindle cell sarcoma. DDL have a propensity for local recurrence, whereas distant metastasis is rarer, and behavior is related to anatomic site, with retroperitoneal neoplasms showing a significantly worse prognosis. Surgical resection remains the mainstay of treatment, and medical options for patients with aggressive recurrent or metastatic disease are limited. DDL share similar genetic abnormalities to WDL, with high-level amplifications of chromosome 12q14-15, including the MDM2 and CDK4 cell cycle oncogenes, and DDL harbor additional genetic changes, particularly coamplifications of 6q23 and 1p32. Novel therapies targeted at the gene products of chromosome 12 are being tested in clinical trials. We review the pathology and genetics of DDL, discussing morphologic patterns, immunohistochemical and genetic findings, the differential diagnosis, and future therapeutic strategies.

Biphenotypic Sinonasal Sarcoma: Case Reports of Diagnostic Findings and Clinical Management of 3 Cases.

BACKGROUND: Biphenotypic sinonasal sarcoma (BSNS) is a rare spindle cell sarcoma distinctly arising in the sinonasal area, with dual myogenic and neural differentiation, and characterised by the presence of PAX3 gene fusion, typically with MAML3. Although the majority may be indolent, up to 25% of cases reported in the literature are locally aggressive, with invasion of adjacent critical structures in the head and neck region. CASE REPORT: We report 3 cases of BSNS reviewed at our institution between 2016-2020 in addition to the current literature. Patient 1 underwent surgery followed by adjuvant radiotherapy but relapsed 24 months later and was not fit for systemic anticancer therapy and managed with palliative care. Due to comorbidities, patient 2 was recommended for active surveillance, with a view to intervening with radiotherapy should there be evidence of clinical progression. At 60 months, the nasal cavity mass remained stable on serial imaging. Patient 3 underwent primary surgical R0 resection and was offered adjuvant post operative radiotherapy 60 Gy/30 fractions/6 weeks but opted for active surveillance and has no clinical or radiological evidence of recurrence 22 months after surgery. CONCLUSION: The primary management for BSNS is surgical resection. We recommend discussing the role of postoperative adjuvant radiotherapy 60 Gy/30 fractions/6 weeks in patients who are fit for treatment. In clinical practice, dose levels will be constrained by surrounding normal tissues. At present, the role of systemic anticancer therapy is undefined. A prospective registry of ultra-rare cases may provide an evidence base with which to select optimal treatment strategies for BSNS in the future.

Toxicity, normal tissue and dose-volume planning parameters for radiotherapy in soft tissue sarcoma of the extremities: A systematic review of the literature.

BACKGROUND: Patients with soft tissue sarcoma of the extremities (STSE) are left with high incidence of toxicities after Radiotherapy (RT). Understanding the normal tissue dose relationship with the development of long-term toxicities may enable better RT planning in order to reduce treatment toxicities for STSE. This systematic review of the literature aims at reporting the incidence of acute and late toxicities and identifying RT delineation guidance the normal tissues structures and dose-volume parameters for STSE. METHODS: A literature search of PUBMED-MEDLINE for studies that reported data on RT toxicity outcomes, delineation guidelines and dose-volume parameters for STSE from 2000 to 2022. Data has been tabulated and reported. RESULTS: Thirty of 586 papers were selected after exclusion criteria. External beam RT prescriptions ranged from 30 to 72 Gy. The majority of studies reported the use of Intensity Modulated RT (IMRT) (27%). Neo-adjuvant RT was used in 40%. The highest long-term toxicities were subcutaneous and lymphoedema, reported when delivering 3DCRT. IMRT had a lower incidence of toxicities. Normal tissue outlining such as weight-bearing bones, skin and subcutaneous tissue, corridor and neurovascular bundle was recommended in 6 studies. Nine studies recommended the use of dose-volume constraints, but only one recommended evidence-based dose-volume constraints. CONCLUSION: Although the literature is replete with toxicity reports, there is a lack of evidence-based guidance on normal tissue and dose-volume parameters and strategies to reduce the normal tissues irradiation when optimising RT plans for STSE are poor compared to other tumour sites.

Controversies in the management of patients with soft tissue sarcoma: Recommendations of the Conference on State of Science in Sarcoma 2022.

BACKGROUND: Owing to the rarity and heterogeneity in biology and presentation, there are multiple areas in the diagnosis, treatment and follow-up of soft tissue sarcoma (STS), with no, low-level or conflicting evidence. METHODS: During the first Consensus Conference on the State of Science in Sarcoma (CSSS), we used a modified Delphi process to identify areas of controversy in the field of sarcoma, to name topics with limited evidence-based data in which a scientific and knowledge gap may remain and a consensus statement will help to guide patient management. We determined scientific questions which need to be addressed in the future in order to generate evidence and to inform physicians and caregivers in daily clinical practice in order to improve the outcomes of patients with sarcoma. We conducted a vote on STS key questions and controversies prior to the CSSS meeting, which took place in May 2022. RESULTS: Sixty-two European sarcoma experts participated in the survey. Sixteen strong consensus (≥95%) items were identified by the experts, as well as 30 items with a ≥75% consensus on diagnostic and therapeutic questions. Ultimately, many controversy topics remained without consensus. CONCLUSIONS: In this manuscript, we summarise the voting results and the discussion during the CSSS meeting. Future scientific questions, priorities for clinical trials, registries, quality assurance, and action by stakeholders are proposed. Platforms and partnerships can support innovative approaches to improve management and clinical research in STS.

Parotid-sparing intensity modulated versus conventional radiotherapy in head and neck cancer (PARSPORT): a phase 3 multicentre randomised controlled trial.

BACKGROUND: Xerostomia is the most common late side-effect of radiotherapy to the head and neck. Compared with conventional radiotherapy, intensity-modulated radiotherapy (IMRT) can reduce irradiation of the parotid glands. We assessed the hypothesis that parotid-sparing IMRT reduces the incidence of severe xerostomia. METHODS: We undertook a randomised controlled trial between Jan 21, 2003, and Dec 7, 2007, that compared conventional radiotherapy (control) with parotid-sparing IMRT. We randomly assigned patients with histologically confirmed pharyngeal squamous-cell carcinoma (T1-4, N0-3, M0) at six UK radiotherapy centres between the two radiotherapy techniques (1:1 ratio). A dose of 60 or 65 Gy was prescribed in 30 daily fractions given Monday to Friday. Treatment was not masked. Randomisation was by computer-generated permuted blocks and was stratified by centre and tumour site. Our primary endpoint was the proportion of patients with grade 2 or worse xerostomia at 12 months, as assessed by the Late Effects of Normal Tissue (LENT SOMA) scale. Analyses were done on an intention-to-treat basis, with all patients who had assessments included. Long-term follow-up of patients is ongoing. This study is registered with the International Standard Randomised Controlled Trial register, number ISRCTN48243537. FINDINGS: 47 patients were assigned to each treatment arm. Median follow-up was 44·0 months (IQR 30·0-59·7). Six patients from each group died before 12 months and seven patients from the conventional radiotherapy and two from the IMRT group were not assessed at 12 months. At 12 months xerostomia side-effects were reported in 73 of 82 alive patients; grade 2 or worse xerostomia at 12 months was significantly lower in the IMRT group than in the conventional radiotherapy group (25 [74%; 95% CI 56-87] of 34 patients given conventional radiotherapy vs 15 [38%; 23-55] of 39 given IMRT, p=0·0027). The only recorded acute adverse event of grade 2 or worse that differed significantly between the treatment groups was fatigue, which was more prevalent in the IMRT group (18 [41%; 99% CI 23-61] of 44 patients given conventional radiotherapy vs 35 [74%; 55-89] of 47 given IMRT, p=0·0015). At 24 months, grade 2 or worse xerostomia was significantly less common with IMRT than with conventional radiotherapy (20 [83%; 95% CI 63-95] of 24 patients given conventional radiotherapy vs nine [29%; 14-48] of 31 given IMRT; p<0·0001). At 12 and 24 months, significant benefits were seen in recovery of saliva secretion with IMRT compared with conventional radiotherapy, as were clinically significant improvements in dry-mouth-specific and global quality of life scores. At 24 months, no significant differences were seen between randomised groups in non-xerostomia late toxicities, locoregional control, or overall survival. INTERPRETATION: Sparing the parotid glands with IMRT significantly reduces the incidence of xerostomia and leads to recovery of saliva secretion and improvements in associated quality of life, and thus strongly supports a role for IMRT in squamous-cell carcinoma of the head and neck. FUNDING: Cancer Research UK (CRUK/03/005).

Radiomic Features From Diffusion-Weighted MRI of Retroperitoneal Soft-Tissue Sarcomas Are Repeatable and Exhibit Change After Radiotherapy.

Background: Size-based assessments are inaccurate indicators of tumor response in soft-tissue sarcoma (STS), motivating the requirement for new response imaging biomarkers for this rare and heterogeneous disease. In this study, we assess the test-retest repeatability of radiomic features from MR diffusion-weighted imaging (DWI) and derived maps of apparent diffusion coefficient (ADC) in retroperitoneal STS and compare baseline repeatability with changes in radiomic features following radiotherapy (RT). Materials and Methods: Thirty patients with retroperitoneal STS received an MR examination prior to treatment, of whom 23/30 were investigated in our repeatability analysis having received repeat baseline examinations and 14/30 patients were investigated in our post-treatment analysis having received an MR examination after completing pre-operative RT. One hundred and seven radiomic features were extracted from the full manually delineated tumor region using PyRadiomics. Test-retest repeatability was assessed using an intraclass correlation coefficient (baseline ICC), and post-radiotherapy variance analysis (post-RT-IMS) was used to compare the change in radiomic feature value to baseline repeatability. Results: For the ADC maps and DWI images, 101 and 102 features demonstrated good baseline repeatability (baseline ICC > 0.85), respectively. Forty-three and 2 features demonstrated both good baseline repeatability and a high post-RT-IMS (>0.85), respectively. Pearson correlation between the baseline ICC and post-RT-IMS was weak (0.432 and 0.133, respectively). Conclusions: The ADC-based radiomic analysis shows better test-retest repeatability compared with features derived from DWI images in STS, and some of these features are sensitive to post-treatment change. However, good repeatability at baseline does not imply sensitivity to post-treatment change.

Shedding a Light on the Challenges of Adolescents and Young Adults with Rhabdomyosarcoma.

Rhabdomyosarcoma (RMS) is a typical tumour of childhood but can occur at any age. Several studies have reported that adolescent and young adult (AYA) patients with RMS have poorer survival than do younger patients. This review discusses the specific challenges in AYA patients with pediatric-type RMS, exploring possible underlying factors which may influence different outcomes. Reasons for AYA survival gap are likely multifactorial, and might be related to differences in tumor biology and intrinsic aggressiveness, or differences in clinical management (that could include patient referral patterns, time to diagnosis, enrolment into clinical trials, the adequacy and intensity of treatment), as well as patient factors (including physiology and comorbidity that may influence treatment tolerability, drug pharmacokinetics and efficacy). However, improved survival has been reported in the most recent studies for AYA patients treated on pediatric RMS protocols. Different strategies may help to further improve outcome, such as supporting trans-age academic societies and national/international collaborations; developing specific clinical trials without upper age limit; defining integrated and comprehensive approach to AYA patients, including the genomic aspects; establishing multidisciplinary tumor boards with involvement of both pediatric and adult oncologists to discuss all pediatric-type RMS patients; developing dedicated projects with specific treatment recommendations and registry/database.

Retrospective observational studies in ultra-rare sarcomas: A consensus paper from the Connective Tissue Oncology Society (CTOS) community of experts on the minimum requirements for the evaluation of activity of systemic treatments.

BACKGROUND: In ultra-rare sarcomas (URS) the conduction of prospective, randomized trials is challenging. Data from retrospective observational studies (ROS) may represent the best evidence available. ROS implicit limitations led to poor acceptance by the scientific community and regulatory authorities. In this context, an expert panel from the Connective Tissue Oncology Society (CTOS), agreed on the need to establish a set of minimum requirements for conducting high-quality ROS on the activity of systemic therapies in URS. METHODS: Representatives from > 25 worldwide sarcoma reference centres met in November 2020 and identified a list of topics summarizing the main issues encountered in ROS on URS. An online survey on these topics was distributed to the panel; results were summarized by descriptive statistics and discussed during a second meeting (November 2021). RESULTS: Topics identified by the panel included the use of ROS results as external control data, the criteria for contributing centers selection, modalities for ensuring a correct pathological diagnosis and radiologic assessment, consistency of surveillance policies across centers, study end-points, risk of data duplication, results publication. Based on the answers to the survey (55 of 62 invited experts) and discussion the panel agreed on 18 statements summarizing principles of recommended practice. CONCLUSIONS: These recommendations will be disseminated by CTOS across the sarcoma community and incorporated in future ROS on URS, to maximize their quality and favor their use as control data when results from prospective studies are unavailable. These recommendations could help the optimal conduction of ROS also in other rare tumors.

Treatments and Outcomes in Oligometastatic Soft Tissue Soft Sarcoma - A Single Centre Retrospective Analysis.

BACKGROUND/AIM: Distinguishing true oligometastatic disease from early polymetastatic disease is vital in patients with soft tissue sarcoma as contemporary treatment strategies differ significantly. Clinical factors such as tumour biology, organ involved, number of lesions, and patient fitness influence clinical decisions. PATIENTS AND METHODS: A retrospective search of a prospective database identified patients with new distant relapse, treated between 2009 and 2012. RESULTS: A total of 223 patients were included, and oligometastases were diagnosed in 81 (36%) patients, which were pulmonary in just over half of cases. These were treated with local therapy in 66 of 89 cases, and 7 patients received subsequent treatment for additional oligometastases. Metastasectomy was the most common treatment modality. A total of 16/66 patients (24%) underwent active surveillance for >6 months prior to local therapy. CONCLUSION: Patients with oligometastatic disease can experience durable disease control with timely multimodality treatment approaches for evolving metastatic disease, where disease biology allows.

Clinical management and outcomes of primary ovarian leiomyosarcoma - Experience from a sarcoma specialist unit.

Ovarian sarcomas account for 1% of all ovarian malignancies and amongst these, primary ovarian leiomyosarcoma is the rarest subtype. Primary ovarian leiomyosarcoma has a very poor prognosis, with less than 20% of patients being alive at 5 years. Only a few cases have been published in the literature and there is very limited knowledge on the clinical behaviour and optimal management of these tumours. We have performed a retrospective analysis of a prospectively maintained database to identify all primary ovarian leiomyosarcoma diagnosed and treated at the Royal Marsden NHS Foundation Trust between 1998 and 2020. Sixteen patients were identified from our database and fifteen were eligible for the analysis. Twelve patients presented with localized disease and underwent initial surgery and three patients had metastatic disease at presentation. Recurrence-free survival post-surgery was 16 months. Eight patients received first-line chemotherapy and four patients received second-line chemotherapy. Two patients had indolent metastatic disease and benefited from local therapies only. The median overall survival in the metastatic setting in our cohort was 51 months, which is consistent with previously published cases. Primary ovarian leiomyosarcoma is an extremely rare malignancy with a poor prognosis. This study is the largest case series of primary ovarian leiomyosarcoma published to date, providing clinically important information regarding survival and metastatic rate as well as treatment outcomes in the metastatic setting.

Intra-Tumoral Pharmacokinetics of Pazopanib in Combination with Radiotherapy in Patients with Non-Metastatic Soft-Tissue Sarcoma.

There is a lack of understanding whether plasma levels of anticancer drugs (such as pazopanib) correlate with intra-tumoral levels and whether the plasma compartment is the best surrogate for pharmacokinetic and pharmacodynamic evaluation. Therefore, we aimed to quantify pazopanib concentrations in tumor tissue, to assess the correlation between tumor concentrations and plasma concentrations and between tumor concentrations and efficacy. In this clinical trial, non-metastatic STS patients were treated with neo-adjuvant concurrent radiotherapy and pazopanib. Plasma samples and tumor biopsies were collected, and pazopanib concentrations were measured using liquid chromatography-tandem mass spectrometry. Twenty-four evaluable patients were included. The median pazopanib tumor concentration was 19.2 µg/g (range 0.149-200 µg/g). A modest correlation was found between tumor concentrations and plasma levels of pazopanib (ρ = 0.41, p = 0.049). No correlation was found between tumor concentrations and percentage of viable tumor cells (p > 0.05); however, a trend towards less viable tumor cells in patients with high pazopanib concentrations in tumor tissue was observed in a categorical analysis. Possible explanations for the lack of correlation might be heterogeneity of the tumors and timing of the biopsy procedure.

Dose Reduction of Preoperative Radiotherapy in Myxoid Liposarcoma: A Nonrandomized Controlled Trial.

IMPORTANCE: Currently, preoperative radiotherapy for all soft-tissue sarcomas is identical at a 50-Gy dose level, which can be associated with morbidity, particularly wound complications. The observed clinical radiosensitivity of the myxoid liposarcoma subtype might offer the possibility to reduce morbidity. OBJECTIVE: To assess whether a dose reduction of preoperative radiotherapy for myxoid liposarcoma would result in comparable oncological outcome with less morbidity. DESIGN, SETTING, AND PARTICIPANTS: The Dose Reduction of Preoperative Radiotherapy in Myxoid Liposarcomas (DOREMY) trial is a prospective, single-group, phase 2 nonrandomized controlled trial being conducted in 9 tertiary sarcoma centers in Europe and the US. Participants include adults with nonmetastatic, biopsy-proven and translocation-confirmed myxoid liposarcoma of the extremity or trunk who were enrolled between November 24, 2010, and August 1, 2019. Data analyses, using both per-protocol and intention-to-treat approaches, were conducted from November 24, 2010, to January 31, 2020. INTERVENTIONS: The experimental preoperative radiotherapy regimen consisted of 36 Gy in once-daily 2-Gy fractions, with subsequent definitive surgical resection after an interval of 4 or more weeks. MAIN OUTCOMES AND MEASURES: As a short-term evaluable surrogate for local control, the primary end point was centrally reviewed pathologic treatment response. The experimental regimen was regarded as a success when 70% or more of the resection specimens showed extensive treatment response, defined as 50% or greater of the tumor volume containing treatment effects. Morbidity outcomes consisted of wound complications and late toxic effects. RESULTS: Among the 79 eligible patients, 44 (56%) were men and the median (interquartile range) age was 45 (39-56) years. Two patients did not undergo surgical resection because of intercurrent metastatic disease. Extensive pathological treatment response was observed in 70 of 77 patients (91%; posterior mean, 90.4%; 95% highest probability density interval, 83.8%-96.4%). The local control rate was 100%. The rate of wound complication requiring intervention was 17%, and the rate of grade 2 or higher toxic effects was 14%. CONCLUSIONS AND RELEVANCE: The findings of the DOREMY nonrandomized clinical trial suggest that deintensification of preoperative radiotherapy dose is effective and oncologically safe and is associated with less morbidity than historical controls, although differences in radiotherapy techniques and follow-up should be considered. A 36-Gy dose delivered in once-daily 2-Gy fractions is proposed as a dose-fractionation approach for myxoid liposarcoma, given that phase 3 trials are logistically impossible to execute in rare cancers. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02106312.

Efficacy of Gemcitabine-based Chemotherapy in Clear Cell Sarcoma of Soft Tissue.

BACKGROUND/AIM: Clear cell sarcoma (CCS) is an aggressive sarcoma subtype, resistant to conventional anthracycline-based chemotherapy and radiation. The diagnosis is often challenging due to similarities with malignant melanoma. PATIENTS AND METHODS: We aimed to analyse the activity of gemcitabine-based chemotherapy in a cohort of patients with CCS treated at the Royal Marsden Hospital. RESULTS: Five patients with metastatic CCS received gemcitabine as first- or second-line systemic therapy. The median time-to-progression was 10 weeks. The median number of cycles of gemcitabine-based therapy was 3 (range=2-7 cycles). Median overall survival in our cohort was 66 months from the initial diagnosis but in the metastatic setting, the overall survival was reduced to 28 months. CONCLUSION: Gemcitabine-based therapy has modest activity in CCS. There remains a significant unmet medical need for novel, effective therapies for this disease.

Telemedicine During the COVID-19 Pandemic: Impact on Care for Rare Cancers.

PURPOSE: Many patients with cancer, often those with rare cancers such as sarcomas, travel long distances to access expert care. The COVID-19 pandemic necessitated widespread changes in delivery of cancer care, including rapid adoption of telemedicine-based care. We aimed to evaluate the impact of telemedicine on patients, clinicians, and care delivery at the Royal Marsden Hospital (RMH) Sarcoma Unit during the pandemic. METHODS: Data were extracted from patient records for all planned outpatient appointments at the RMH Sarcoma Unit from March 23 to April 24, 2020. Patients and clinicians completed separate questionnaires to understand their experiences. RESULTS: Of 379 planned face-to-face appointments, 283 (75%) were converted to telemedicine. Face-to-face appointments remained for patients who needed urgent start of therapy or performance status assessment. Patients lived on average > 1.5 hours from RMH. Patient satisfaction (n = 108) with telemedicine was high (mean, 9/10), and only 48% (n = 52/108) would not want to hear bad news using telemedicine. Clinicians found telemedicine efficient, with no associated increased workload, compared with face-to-face appointments. Clinicians indicated lack of physical examination did not often affect care provision when using telemedicine. Most clinicians (n = 17; 94%) believed telemedicine use was practice changing; congruently, 80% (n = 86/108) of patients desired some telemedicine as part of their future care, citing reduced cost and travel time. CONCLUSION: Telemedicine can revolutionize delivery of cancer care, particularly for patients with rare cancers who often live far away from expert centers. Our study demonstrates important patient and clinician benefits; assessment of longer-term impact on patient outcomes and health care systems is needed.

The Role of Local Therapy in Multi-focal Epithelioid Haemangioendothelioma.

BACKGROUND/AIM: Epithelioid haemangioendothelioma (EHE) is a rare tumor with a wide spectrum of clinical behavior. There is no consensus on the role of local therapy in symptomatic, multi-focal disease. PATIENTS AND METHODS: A retrospective review of patients presenting to the Royal Marsden Hospital between January 2000 and December 2017 was conducted. RESULTS: Fifty-three patients with EHE were identified, of which 18 patients (34.0%) received local therapy, and 11 patients (20.8%) underwent active surveillance. A variety of local treatment modalities were used with few toxicities, and local recurrence was managed with other local treatments or systemic therapy. Distal disease progression was infrequent (n=4, 7.5%). Patients who developed pleural effusion (n=5, 9.4%) had poor outcome irrespective of treatment. CONCLUSION: Local therapy has a role in a selected patient group managed in a multidisciplinary setting, including patients with indolent disease, and patients with a solitary area of progression/symptomatic disease.