Active surveillance and emerging medical treatment options for desmoid: when and for whom?

PURPOSE OF REVIEW: This article discusses the evolving approaches to desmoid tumors management, shedding light on recent developments. RECENT FINDINGS: Active surveillance has become the primary approach for managing primary peripheral desmoid tumors. This strategy was initially based on evidence from retrospective studies. Roughly 50% of cases managed with active surveillance show spontaneous stabilization or regression. Recent prospective trials conducted in Italy, The Netherlands, and France (2022-2023) confirm the efficacy of active surveillance, revealing 3-year progression-free survival rates ranging from 53.4 to 58%. For the patients under active surveillance, decisions regarding treatment are based on significant tumor growth or progressive symptoms. Moreover, three contemporary randomized trials investigated medical treatments for progressive or recurrent desmoid tumors. Sorafenib, pazopanib, and nirogacestat demonstrated clinical activity, as evidenced by favorable progression-free survival and objective response rates. SUMMARY: Active surveillance has solidified its position as the primary management approach for desmoid tumors, validated by three robust prospective studies. Three recent randomized trials explored medical treatment for progressive or recurrent desmoid tumors, revealing promising clinical activities.

How to develop new systemic treatments in ultra-rare cancers with high unmet needs? The case of alveolar soft-part sarcoma.

Developing new drugs or generating evidence for existing drugs in new indications for ultra-rare cancers is complex and carries a high-risk of failure. This gets even harder in ultra-rare tumours, which have an annual incidence of 1 per 1,000,000 population or less. Here, we illustrate the problem of adequate evidence generation in ultra-rare tumours, using Alveolar Soft-Part Sarcomas (ASPS) - an ultra-rare sarcoma newly diagnosed in approximately 60 persons a year in the European Union - as an exemplar case showing challenges in development despite being potentially relevant for classes of agents. We discuss some possible approaches for addressing such challenges, especially focussing on constructive collaboration between academic groups, patients and advocates, drug manufacturers, and regulators to optimise drug development in ultra-rare cancers. This article, written by various European stakeholders, proposes a way forward to ultimately get better options for patients with ultra-rare cancers.

Geriatric Assessment of Older Patients Receiving Trabectedin in First-Line Treatment for Advanced Soft Tissue Sarcomas: The E-TRAB Study from The German Interdisciplinary Sarcoma Group (GISG-13).

E-TRAB was a non-interventional, prospective trial investigating the feasibility and predictive value of geriatric assessments (GA) in older STS patients treated with trabectedin as first-line therapy. Primary endpoints were overall survival (OS), quality of life and individual clinical benefit assessed by the patient-reported outcome measures QLQ-C30 and PRO-CTCAE. Further, several GA tools were applied and correlated with clinical outcomes and treatment-related toxicities. The final analyses included 69 patients from 12 German-speaking sites. The median age of patients was 78 years (range: 55 to 88). Baseline data on PROs and GA identified a diverse population of older patients with respect to their global health status, although a large proportion of them suffered from limitations, required geriatric help and had a high risk of morbidity. The Cancer and Age Research Group (CARG) score classified 38%, 29% and 23% of the patients with low, intermediate and high risks for therapy-related side effects, respectively. Median OS was 11.2 months [95%CI: 5.6; 19.4]. The study confirmed that trabectedin as first-line treatment in older patients with STS has an acceptable and manageable safety profile. Potential prognostic factors for clinical outcome and therapy-related toxicity were identified among the GA tools. Long Timed Up and Go (TUG) showed a significant correlation to OS and early death, whereas a high CARG score (>9) was associated with an increase in unplanned hospitalizations and the incidence of toxicities grade ≥ 3.

Trauma and sporadic desmoid tumor development: An approach toward real incidence and aspects of causality.

OBJECTIVES: The development of desmoid tumors (DT) is associated with trauma, which is an aspect with medicolegal relevance. The objective of this study was to analyze the proportion and type of trauma (surgical, blunt/fracture, implants), its lag time, and mutations of the CTNNB1 gene in patients with sporadic DT. METHODS: We analyzed a prospectively kept database of 381 females and 171 males, median age at disease onset 37.7 years (females) and 39.3 years (males) with a histologically confirmed DT. Patients with germline mutation of the APC gene were excluded. Details of the history particularly of traumatic injuries to the site of DT were provided by 501 patients. RESULTS: In 164 patients (32.7%), a trauma anteceding DT could be verified with a median lag time of 22.9 months (SD, 7.7 months; range, 9-44 months). A prior surgical procedure was relevant in 98 patients, a blunt trauma in 35 patients, a punctuated trauma (injections, trocar) in 18 patients, and site of an implant in 10 patients. In 220 patients, no trauma was reported (43.9%), and 58 females (11.6%) had a postpregnancy DT in the rectus abdominis muscle. In 42 patients (8.4%), data were inconclusive. The distribution of mutations in the CTNNB1 gene (codon 41 vs. 45) was similar in patients with and without a history of trauma before DT development. CONCLUSIONS: A significant subgroup of patients suffers from a trauma-associated DT, predominantly at a prior surgical site including implants to breast or groin, accounting for 77.9% of the cases, whereas blunt trauma was responsible in 22.1%. We found no data to support that trauma-associated DT have different molecular features in the CTNNB1 gene.

Health related Quality of Life over time in German sarcoma patients. An analysis of associated factors - results of the PROSa study.

Introduction: Sarcomas are rare cancers and very heterogeneous in their location, histological subtype, and treatment. Health-Related Quality of Life (HRQoL) of sarcoma patients has rarely been investigated in longitudinal studies. Methods: Here, we assessed adult sarcoma patients and survivors between September 2017 and February 2020, and followed-up for one year in 39 study centers in Germany. Follow-up time points were 6 (t1) and 12 months (t2) after inclusion. We used a standardized, validated questionnaire (the European Organisation for Research and Treatment of Cancer Quality of Life Core Instrument (EORTC QLQ-C30) and explored predictors of HRQoL in two populations (all patients (Analysis 1), patients in ongoing complete remission (Analysis 2)) using generalized linear mixed models. Results: In total we included up to 1111 patients at baseline (915 at t1, and 847 at t2), thereof 387 participants were in complete remission at baseline (334 at t1, and 200 at t2). When analyzing all patients, HRQoL differed with regard to tumor locations: patients with sarcoma in lower extremities reported lower HRQoL values than patients with sarcomas in the upper extremities. Treatment which included radiotherapy and/or systemic therapy was associated with lower HRQoL. For patients in complete remission, smoking was associated with worse HRQoL-outcomes. In both analyses, bone sarcomas were associated with the worst HRQoL values. Being female, in the age group 55-<65 years, having lower socioeconomic status, and comorbidities were all associated with a lower HRQoL, in both analyses. Discussion: HRQoL increased partially over time since treatment and with sporting activities. HRQoL improved with time since treatment, although not in all domains, and was associated with lifestyle and socioeconomic factors. Bone sarcomas were the most affected subgroup. Methods to preserve and improve HRQoL should be developed for sarcoma patients.

Ten recommendations for sarcoma surgery: consensus of the surgical societies based on the German S3 guideline "Adult Soft Tissue Sarcomas".

PURPOSE: The evidence-based (S3) guideline "Adult Soft Tissue Sarcomas" (AWMF Registry No. 032/044OL) published by the German Guideline Program in Oncology (GGPO) covers all aspects of sarcoma treatment with 229 recommendations. Representatives of all medical specialties involved in sarcoma treatment contributed to the guideline. This paper compiles the most important recommendations for surgeons selected by delegates from the surgical societies. METHODS: A Delphi process was used. Delegates from the surgical societies involved in guideline process selected the 15 recommendations that were most important to them. Votes for similar recommendations were tallied. From the resulting ranked list, the 10 most frequently voted recommendations were selected and confirmed by consensus in the next step. RESULTS: The statement "Resection of primary soft tissue sarcomas of the extremities should be performed as a wide resection. The goal is an R0 resection" was selected as the most important term. The next highest ranked recommendations were the need for a preoperative biopsy, performing preoperative MRI imaging with contrast, and discussing all cases before surgery in a multidisciplinary sarcoma committee. CONCLUSION: The evidence-based guideline "Adult Soft Tissue Sarcomas" is a milestone to improve the care of sarcoma patients in Germany. The selection of the top ten recommendations by surgeons for surgeons has the potential to improve the dissemination and acceptance of the guideline and thus improve the overall outcome of sarcoma patients.

Sarcoma Research with Cancer Registry Data: Data and Peculiarities of Germany in the Light of Other Countries.

INTRODUCTION: Sarcomas are documented in population-based and in clinic-associated databases. This study evaluated the status quo regarding the potential and obstacles of cancer registry-based research on sarcomas exemplified by Germany in comparison to similar databases in the US and Europe. Completeness and quality of data are discussed based on statistical analyses of a pooled data set established for the German Cancer Congress 2020. METHODS: We analyzed data derived from 16 German institutions (federal state cancer registries and some facility-based registries). Malignant sarcomas in adults diagnosed between 2000 and 2018 with information on histology were grouped according to the WHO classification of soft tissue and bone tumors. Descriptive analyses of the study population regarding the distribution of age, sex, histology, localization of primary tumors, and metastases were performed. Survival for the ten most frequent histological groups and UICC stages was evaluated according to Kaplan-Meier and Cox regression. Time interval between surgery and subsequent radiation was calculated. RESULTS: The initial data set contained 35,091 sarcomas. After several steps of data cleaning, 28,311 patients with known sex and unambiguous assignment to a histological subgroup remained (13,682 women and 14,629 men). Between 40 and 54 years, women were more likely to develop sarcomas, whereas in the older age groups more men were affected. Gastrointestinal stromal tumors, fibroblastic, and myofibroblastic tumors, smooth muscle tumors (mostly non-uterine leiomyosarcomas), and adipocytic tumors represented 48% of all sarcomas. Preferential sites for fibrosarcomas were the limbs, the trunk, and the head and neck region. The liposarcoma occurred most frequently on the trunk and limbs. Distant primary metastases were mostly located in the lung (43%), followed by the liver (14%), and bones (13%). Vascular and smooth muscle tumors showed the worst survival prognosis (5-year survival: approx. 15%, median survival approx. 8-16 months), whereas in low stages, the probability of survival of many sarcoma patients was beyond 5 years. Adjuvant radiotherapy was applied within 90 days in 71% of patients (n = 2,534). CONCLUSION: Our results correspond to the data from the literature. However, a lack of data quality and completeness hampers further meaningful analyses, especially nonspecific or missing information about morphology and stage. Compared to some other countries, a comprehensive database is presently missing in Germany. However, currently, there are important efforts and legislative initiatives to create a comprehensive database on a national level within the near future.

Psychological and social challenges of patients with locally advanced and metastatic gastrointestinal stromal tumours (GIST) on long-term treatment with tyrosine kinase inhibitors: a qualitative study with patients and medical oncologists.

PURPOSE: Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of locally advanced and metastatic gastrointestinal stromal tumours (GISTs). Patients are experiencing prolonged survival but often at the expense of their health-related quality of life. It is not only the physical side effects that impact GIST patients' daily lives but also the psychological and social challenges they have to deal with. This qualitative study aimed to explore the psychological and social life challenges of GIST patients with locally advanced and metastatic disease on ≥ 5 years TKI treatment. METHODS: Semi-structured interviews with 15 locally advanced and/or metastatic GIST patients and 10 medical oncologists with experience of delivering care to this specific patient group were conducted. Thematic analysis was used to interpret the data. RESULTS: Psychological challenges expressed by participants concerned fears, scanxiety, negative change in emotion and mood, doubts about their treatment and follow-up, living with uncertainty, lack of understanding from others or healthcare professionals, and constantly being reminded of their illness. Challenges regarding social health included financial difficulties, challenges in relationships, concerns about fertility and parenting, work, and impact on social activities. CONCLUSION: The reported psychological and social challenges can significantly hamper the overall quality of life of GIST patients. Some challenges were clearly underreported and hardly recognized by medical oncologist, as they may tend to focus on the physical side effects and clinical outcomes of treatment. Therefore, it is essential to take the patient's perspective into account in research and clinical practice to ensure optimal care for this patient group.

New treatments for desmoid tumors.

PURPOSE OF REVIEW: Desmoid tumor is a rare disease of intermediate malignancy characterized by a locally aggressive monoclonal, fibroblastic proliferation and accompanied by a variable and often unpredictable clinical course. The purpose of this review is to give an overview on the emerging new systemic treatment options for this intriguing disease for which no established or approved drugs are available yet. RECENT FINDINGS: Over decades, surgical resection has been the established initial treatment approach; however, more recently, a paradigm shift has been introduced towards a more conservative treatment strategy. Almost 10 years ago, The Desmoid Tumor Working Group has initiated a consensus process initially in Europe and then globally with the intention to harmonize the therapeutic strategy amongst clinicians and set up management recommendations for desmoid tumor patients. SUMMARY: This review will summarize and focus on the latest emerging impressive data on the use of gamma secretase inhibitors in this disease paving a possible future perspective in the treatment armamentarium for desmoid tumor patients.

Nirogacestat, a γ-Secretase Inhibitor for Desmoid Tumors.

BACKGROUND: Desmoid tumors are rare, locally aggressive, highly recurrent soft-tissue tumors without approved treatments. METHODS: We conducted a phase 3, international, double-blind, randomized, placebo-controlled trial of nirogacestat in adults with progressing desmoid tumors according to the Response Evaluation Criteria in Solid Tumors, version 1.1. Patients were assigned in a 1:1 ratio to receive the oral γ-secretase inhibitor nirogacestat (150 mg) or placebo twice daily. The primary end point was progression-free survival. RESULTS: From May 2019 through August 2020, a total of 70 patients were assigned to receive nirogacestat and 72 to receive placebo. Nirogacestat had a significant progression-free survival benefit over placebo (hazard ratio for disease progression or death, 0.29; 95% confidence interval, 0.15 to 0.55; P<0.001); the likelihood of being event-free at 2 years was 76% with nirogacestat and 44% with placebo. Between-group differences in progression-free survival were consistent across prespecified subgroups. The percentage of patients who had an objective response was significantly higher with nirogacestat than with placebo (41% vs. 8%; P<0.001), with a median time to response of 5.6 months and 11.1 months, respectively; the percentage of patients with a complete response was 7% and 0%, respectively. Significant between-group differences in secondary patient-reported outcomes, including pain, symptom burden, physical or role functioning, and health-related quality of life, were observed (P≤0.01). Frequent adverse events with nirogacestat included diarrhea (in 84% of the patients), nausea (in 54%), fatigue (in 51%), hypophosphatemia (in 42%), and maculopapular rash (in 32%); 95% of adverse events were of grade 1 or 2. Among women of childbearing potential receiving nirogacestat, 27 of 36 (75%) had adverse events consistent with ovarian dysfunction, which resolved in 20 women (74%). CONCLUSIONS: Nirogacestat was associated with significant benefits with respect to progression-free survival, objective response, pain, symptom burden, physical functioning, role functioning, and health-related quality of life in adults with progressing desmoid tumors. Adverse events with nirogacestat were frequent but mostly low grade. (Funded by SpringWorks Therapeutics; DeFi ClinicalTrials.gov number, NCT03785964.).

Electronic Patient Reported Outcome (ePRO) Measures in Patients with Soft Tissue Sarcoma (STS) Receiving Palliative Treatment.

The PazoQoL prospective, randomized, controlled, multicenter study was designed to continuously assess global health related quality of life (HRQoL) during treatment with pazopanib or physician-preferred chemotherapy over a 9-week period. The questionnaires were completed by the patients at home with great reliability during this time period. Continuous electronic patient reported outcome (ePRO) enabled early detection of the onset of deterioration and timely initiation of countermeasures. The Cancer Therapy Satisfaction Questionnaire (CTSQ) showed high interindividual variability and decline over a 9-week period, whereas the Time Trade-off (TTO) proved to be an efficient method for assessing individual benefit from cancer therapy. In our cohort, the TTO clearly demonstrated that the prolongation of life and the side effect profile of continued therapy were not as satisfactory as expected by patients when starting a new therapy. Although the study had to be stopped early due to the pandemic, our findings could translate into clinical practice without much effort and outside of a trial.

A post hoc analysis of the EPAZ trial: The role of geriatric variables in elderly soft tissue sarcoma patients on toxicity and outcome.

OBJECTIVE: The EPAZ study (NCT01861951) showed recently that pazopanib was non-inferior to doxorubicin in patients ≥60 years treated in first line for advanced soft tissue sarcoma . The current post-hoc analysis aimed to assess the prognostic impact of frailty. METHODS: Geriatric assessments were evaluated at baseline. Age >75 years, liposarcoma, ECOG = 2, G8 ≤14, instrumental activities of daily living (IADL) ≥1 and Charlson Comorbidity Index ≥2 were tested for their impact on progression-free survival (PFS), overall survival (OS), CTCAE grade 3/4 adverse events (AEs) or serious AEs (SAEs), using univariate and multivariate analysis models. RESULTS: univariate analysis showed an increased risk of grade 3/4 AEs and SAEs for ECOG = 2, G8 score ≤14 or IADL ≥1, independent of treatment. The multivariate analysis exhibited for pazopanib a significantly reduced risk for grade 3/4 AEs (HR 0.53; p = 0.033), and in patients with G8 ≤14 an increased risk for SAEs (HR 2.67; p = 0.011). In the multivariate analysis, G8 ≤14 was a negative prognostic factor for PFS (HR 1.82; p = 0.009) and IADL ≥1 for OS (HR 2.02; p = 0.007). ECOG = 2 was the strongest negative predictor for PFS (HR 4.39; p = 0.001) and OS (HR 3.74; p = 0.004). Neither age nor Charlson Comorbidity Index showed any impact on PFS, OS, incidence of grade 3/4 AEs or SAEs. CONCLUSIONS: This post hoc analysis demonstrated that age is not a denominator for outcome or toxicity in elderly patients with soft tissue sarcoma . Instead, geriatric and functional assessments should be used to counsel patients and tailor therapy to individual needs. Moreover, pazopanib has a reduced risk for grade 3/4 AEs compared to doxorubicin.

Working situation and burden of work limitations in sarcoma patients: results from the multi-center prospective PROSa study.

PURPOSE: We investigated predictors of limitations in work performance, odds of drop out of work, and odds of receiving disability pension in sarcoma patients. METHODS: We measured clinical and sociodemographic data in adult sarcoma patients and recorded if the patients received a (1) disability pension at baseline or (2) had dropped out of work 1 year after initial assessment. (3) Work limitations were assessed using the Work-limitations questionnaire (WLQ©). We analyzed exploratively. RESULTS: (1) Amongst 364 analyzed patients, odds to receive a disability pension were higher in patients with abdominal tumors, older patients, high grade patients and with increasing time since diagnosis. (2) Of 356 patients employed at baseline, 21% (n = 76) had dropped out of work after 1 year. The odds of dropping out of work were higher in bone sarcoma patients and in patients who received additive radiotherapy ± systemic therapy compared with patients who received surgery alone. Odds of dropping out of work were less amongst self-employed patients and dropped with increasing time since diagnosis. (3) Work limitations were higher in woman and increased with age. Patients with bone and fibrous sarcomas were more affected than liposarcoma patients. Patients with abdominal tumors reported highest restrictions. Sarcoma treatment in the last 6 months increased work limitations. CONCLUSION: Work limitations, drop out of work and dependence on a disability pension occurs frequently in patients with sarcoma adding to the burden of this condition. We were able to identify vulnerable groups in both the socioeconomic and disease categories.

Comprehensive molecular profiling of sarcomas in adolescent and young adult patients: Results of the EORTC SPECTA-AYA international proof-of-concept study.

BACKGROUND: Adolescent and young adult (AYA) patients with cancer are poorly recruited to molecularly targeted trials and have not witnessed the advances in cancer treatment and survival seen in other age groups. We report here a pan-European proof-of-concept study to identify actionable alterations in some of the worst prognosis AYA cancers: bone and soft tissue sarcomas. DESIGN: Patients aged 12-29 years with newly diagnosed or recurrent, intermediate or high-grade bone and soft tissue sarcomas were recruited from six European countries. Pathological diagnoses were centrally reviewed. Formalin-fixed tissues were analysed by whole exome sequencing, methylation profiling and RNA sequencing and were discussed in a multidisciplinary, international molecular tumour board. RESULTS: Of 71 patients recruited, 48 (median 20 years, range 12-28) met eligibility criteria. Central pathological review confirmed, modified and re-classified the diagnosis in 41, 3, and 4 cases, respectively. Median turnaround time to discussion at molecular tumour board was 8.4 weeks. whole exome sequencing (n = 48), methylation profiling (n = 44, 85%) and RNA sequencing (n = 24, 50%) led to therapeutic recommendations for 81% patients, including 4 with germ line alterations. The most common were for agents targeted towards tyrosine kinases (n = 20 recommendations), DNA repair (n = 18) and the PI3K/mTOR/AKT pathway (n = 15). Recommendations were generally based on weak evidence such as activity in a different tumour type (n = 68, 61%), reflecting the dearth of relevant molecular clinical trial data in the same tumour type. CONCLUSIONS: We demonstrate here that comprehensive molecular profiling of AYA patients' samples is feasible and deliverable in a European programme.

EJSO educational Special issue from the TARPSWG - Standard medical treatment and new options in retroperitoneal sarcoma.

Retroperitoneal soft tissue sarcomas mainly consist histologically of liposarcomas and leiomyosarcomas. For the liposarcoma subgroup, the local relapse rate seems to determine patients' overall prognosis. In contrast, leiomyosarcoma patients are challenged by the development of metastatic disease; therefore, effective systemic therapies are the cornerstone to improve patients' outcome. No doubt, the limited number of active regimens currently available makes the treatment of patients with locally advanced and/or metastatic disease challenging and results in the overall poor prognosis of this population. In this European Journal of Surgical Oncology Educational Special Issue from the Transatlantic Australasian RetroPeritoneal Sarcoma Working Group (TARPSWG), we aim to summarize state-of-the-art systemic treatments for patients with retroperitoneal sarcomas with a focus on the locally advanced and metastatic disease setting including conventional standard chemotherapies as well as new innovative treatment approaches in order to identify current unmet medical needs guiding the sarcoma community to initiate appropriate translational research projects and design innovative clinical trials.

New benchmarks to design clinical trials with advanced or metastatic liposarcoma or synovial sarcoma patients: An EORTC - Soft Tissue and Bone Sarcoma Group (STBSG) meta-analysis based on a literature review for soft-tissue sarcomas.

BACKGROUND: Recently, we performed a meta-analysis based on a literature review for STS trials (published 2003-2018, ≥10 adult patients) to update long-standing reference values for leiomyosarcomas. This work is extended for liposarcomas (LPS) and synovial sarcomas (SS). MATERIALS AND METHODS: Study endpoints were progression-free survival rates (PFSRs) at 3 and 6 months. Trial-specific estimates were pooled per treatment line (first-line or pre-treated) with random effects meta-analyses. The choice of the therapeutic benefit to target in future trials was guided by the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS). RESULTS: Information was acquired for 1030 LPS patients (25 trials; 7 first-line, 17 pre-treated, 1 both) and 348 SS patients (13 trials; 3 first-line, 10 pre-treated). For LPS, the overall pooled first-line PFSRs were 69% (95%-CI 60-77%) and 56% (95%-CI 45-67%) at 3 and 6 months, respectively. These rates were 49% (95%-CI 40-57%)/28% (95%-CI 22-34%) for >1 lines. For SS, first-line PFSRs were 74% (95%-CI 58-86%)/56% (95%-CI 31-78%) at 3 and 6 months, and pre-treated rates were 45% (95%-CI 34-57%)/25% (95%-CI 16-36%). Following ESMO-MCBS guidelines, the minimum values to target are 79% and 69% for first-line LPS (82% and 69% for SS) at 3 and 6 months. For pre-treated LPS, recommended PFSRs at 3 and 6 months suggesting drug activity are 63% and 44% (60% and 41% for SS). CONCLUSIONS: New benchmarks are proposed for advanced/metastatic LPS or SS to design future histology-specific phase II trials. More data are needed to provide definitive thresholds for the different LPS subtypes.

Distress in soft-tissue sarcoma and gastrointestinal stromal tumours patients-Results of a German multicentre observational study (PROSa).

OBJECTIVE: Soft tissue sarcomas (STS) and gastrointestinal stromal tumours (GIST) are a group of rare malignant tumours with a high and heterogenous disease burden. As evidence is scarce, we analysed the prevalence of increased emotional distress and identified distress-associated factors in these patients. METHODS: The PROSa-study (Burden and medical care of sarcoma) was conducted between 2017 and 2020 in 39 study centres. Cross-sectional data from adult STS and GIST patients were analysed. Distress was measured with the Patient Health Questionnaire (PHQ-4). The relation of socioeconomic and clinical factors with distress was explored in adjusted logistic regression models. RESULTS: Among 897 patients, 17% reported elevated anxiety and 19% reported depression. Unemployed patients (odds ratio [OR] 6.6; 95% CI 2.9-15.0), and those with a disability pension (OR 3.1; 95% CI 1.9-5.0) were more likely to experience distress compared to employed patients. Also, patients with a disability pass had higher odds of increased distress than those without (OR 1.8; 95% CI 1.2-2.7). Lowest distress was observed in patients 2 to <5 years and ≥5 years after diagnosis (comparison: <6 months) (OR 0.4; 95% CI 0.2-0.6) and (0.3; 95% CI 0.2-0.6). Patients with thoracic STS (vs. lower limbs) had twice the odds to experience distress (OR 2.0; 95% CI 1.1-3.6). Distress was seen almost twice as often in patients with progressive disease (vs. complete remission) (OR 1.7; 95% CI 1.1-2.8). CONCLUSION: The prevalence of elevated distress in STS and GIST patients is high. In unemployed patients, in those with a disability pension and in newly diagnosed patients a noticeable increase was observed. Clinicians should be aware of these factors and consider the social aspects of the disease.

Activity of Cabazitaxel in Metastatic or Inoperable Locally Advanced Dedifferentiated Liposarcoma: A Phase 2 Study of the EORTC Soft Tissue and Bone Sarcoma Group (STBSG).

Importance: Treatment options for patients with unresectable and/or metastatic dedifferentiated liposarcoma (DDLPS) are limited. New drugs are required. Objective: To assess whether cabazitaxel demonstrated sufficient antitumor activity in patients with metastatic or inoperable locally advanced DDLPS to justify further investigation in a phase 3 setting. Design, Setting, and Participants: This international multicenter, open-label single-arm phase 2 trial was conducted at 10 institutions in 4 European countries from March 2015 to March 2019. Eligible patients had to have metastatic or locally advanced histologically proven DDLPS with evidence of disease progression within the past 6 months and had to have received no more than 1 previous line of chemotherapy. Interventions: After mandatory central review of tumor blocks, if the DDLPS diagnosis was confirmed, patients started treatment within 72 hours after registration. Cabazitaxel was administered at a dose of 25 mg/m2 IV infusion over 1 hour every 21 days until intolerance, progression, or withdrawal of consent. Main Outcomes and Measures: The primary end point was progression-free survival (PFS) rate at 12 weeks per RECIST 1.1. Based on a Simon 2-stage design, at least 4 of 17 (stage 1) and 11 of 37 (stage 2) eligible and evaluable patients who were progression free at 12 weeks were needed. The final analysis report was completed on November 17, 2021. Results: Forty patients were registered, with 2 patients being ineligible. The number of cycles ranged from 1 to 30, with a median of 5; 26 patients (65%) received at least 4 cycles of cabazitaxel. Progression-free survival at 12 weeks was 55%, achieving the primary study end point. At a median follow-up of 21.6 months, median PFS was 6 months and median OS 21 months. Response rate (RR) was 8% with 1 clinical response (CR) and 2 partial responses (PR). Twenty-three (60.5%) patients had a stable disease (SD). Disease control (PR+SD) was achieved in 26 patients (68%). Conclusions and Relevance: This nonrandomized phase 2 clinical trial met its primary end point, with 21 of 38 patients (55%) being progression free at 12 weeks. These results suggest important activity of cabazitaxel in patients with metastatic or inoperable locally advanced DDLPS. The drug is worth being further studied in these tumors in a phase 3 setting.

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.

Transferability of Health-Related Quality of Life Data of Large Observational Studies to Clinical Practice: Comparing Retroperitoneal Sarcoma Patients from the PROSa Study to a TARPS-WG Cohort.

INTRODUCTION: Health-related quality of life (HRQoL) is crucial for shared decision-making. The "Patient-Reported Outcome measures in Sarcoma" (PROSa) study evaluated HRQoL in general. We evaluated the transferability of PROSa data to clinical practice for the subgroup of retroperitoneal sarcoma (RPS). METHODS: To obtain a PROSa-RPS cohort, we excluded patients with bone sarcomas and gastrointestinal stromal tumors from the complete PROSa cohort (n = 1,113), limited tumor localization to trunk and retroperitoneum, and excluded patients with metastases. We evaluated the HRQoL data of the resulting 76 patients and compared their clinical data to those of the Transatlantic Autralasian Retroperitoneal Sarcoma Working Group (TARPS-WG, n = 1,007). RESULTS: Confidence intervals for patient sex, histological subtype (LPS vs. non-LPS), grading (G1 vs. G2/3), surgical margins (R2 vs. no R2), and perioperative chemo- and radiotherapy (yes vs. no) were overlapping in both cohorts. EORTC QLQ-C30 from RPS-PROSa patients demonstrated that two-thirds had clinically relevant restrictions in physical functioning. Two-thirds reported dyspnea, followed by fatigue and pain. CONCLUSION: Clinical data from RPS-PROSa patients are comparable to those of an RPS reference cohort from expert centers. We believe that HRQoL data of RPS patients extracted from PROSa are transferable to clinical practice.