Management of patients with rare adult solid cancers: objectives and evaluation of European reference networks (ERN) EURACAN.

About 500,000 patients with rare adult solid cancers (RASC) are diagnosed yearly in Europe. Delays and unequal quality of management impact negatively their survival. Since 2017, European reference networks (ERN) aim to improve the quality of care of patients with rare disease. The steering committee of EURACAN, including physicians, researchers and patients review here the previous actions, present objectives of the ERN EURACAN dedicated to RASC. EURACAN promoted management in reference centres, and equal implementation of excellence and innovation in Europe and developed 22 clinical practice guidelines (CPGs). Additionally, fourteen information brochures translated in 24 EU languages were developed in collaboration with patient advocacy groups (ePAGs) and seventeen training session were organized. Nevertheless, connections to national networks in the 26 participating countries (106 centres), simplification of cross-border healthcare, international multidisciplinary tumour boards, registries and monitoring of the quality of care are still required. In this Health Policy, evaluation criteria of the performances of the network and of health care providers are proposed.

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.

Variation in response rates to isolated limb perfusion in different soft-tissue tumour subtypes: an international multi-centre study.

OBJECTIVE: The aim of this study was to investigate the response rates of different extremity soft-tissue sarcoma subtypes (eSTS) after isolated limb perfusion (ILP), based on an international multi-centre study. MATERIALS AND METHODS: The retrospective cohort comprised eSTS patients from 17 specialised ILP centres that underwent melphalan-based ILP, with or without recombinant human tumour necrosis factor (rhTNFα) (TM-ILP and M-ILP, respectively). Response was measured on imaging (magnetic resonance imaging) and/or clinical response, for which M-ILPs were excluded. RESULTS: A total of 1109 eSTS patients were included. The three most common histological subtypes were undifferentiated pleomorphic sarcoma (17%, n = 184), synovial sarcoma (16%, n = 175) and myxofibrosarcoma (8%, n = 87). rhTNFα was used in 93% (TM-ILP) and resulted in a significantly better overall response rate (ORR, p = 0.031) and complete responses (CR, p < 0.001) in comparison to M-ILP, without significant differences among histological subgroups. The ORR of TM-ILP was 68%, including 17% CR. Also, 80% showed progressive disease. Significantly higher response rates were shown for Kaposi sarcoma (KS) with 42% CR and 96% ORR (both p < 0.001), and significantly higher CR rates for angiosarcoma (AS, 45%, p < 0.001) and clear cell sarcoma (CCS, 31%, p = 0.049). ILP was followed by resection ≤ 6 months in 80% of the patients. The overall limb salvage rate was 88%, without significant differences among histological subgroups, but was significantly higher for ILP responders compared to non-responders (93% versus 76%, p < 0.001). CONCLUSION: ILP resulted in high response and LRS among all eSTS subtypes, however, with significant differences between subtypes with most promising results for KS, AS and CCS.

Histology of the Primary Tumor Correlates with False Positivity of Integrated 18F-FDG-PET/CT Lymph Node Staging in Resectable Lung Cancer Patients.

This study aimed to evaluate the diagnostic accuracy and false positivity rate of lymph node (LN) staging assessed by integrated 18F-fluorodeoxyglucose positron emission computed tomography (18F-FDG-PET/CT) in patients with operable lung cancer to the tumor histology. In total, 129 consecutive patients with non-small-cell lung cancer (NSCLC) undergoing anatomical lung resections were included. Preoperative LN staging was evaluated in the relationship to the histology of the resected specimens (group 1: lung adenocarcinoma/LUAD; group 2: squamous cell carcinoma/SQCA). Statistical analysis was performed by the Mann-Whitney U-test, the chi2 test, and binary logistic regression analysis. To establish an easy-to-use algorithm for the identification of LN false positivity, a decision tree including clinically meaningful parameters was generated. In total, 77 (59.7%) and 52 (40.3%) patients were included in the LUAD and SQCA groups, respectively. SQCA histology, non-G1 tumors, and tumor SUVmax > 12.65 were identified as independent predictors of LN false positivity in the preoperative staging. The corresponding ORs and their 95% CIs were 3.35 [1.10-10.22], p = 0.0339; 4.60 [1.06-19.94], p = 0.0412; and 2.76 [1.01-7.55], and p = 0.0483. The preoperative identification of false-positive LNs is an important aspect of the treatment regimen for patients with operable lung cancer; thus, these preliminary findings should be further evaluated in larger patient cohorts.

Local Therapies for Metastatic Sarcoma: Why, When, and How?

Management of patients with advanced sarcoma has been evolving in recent decades, from a one-fit-all perspective to a more refined, personalized, and multidisciplinary approach. In parallel, the evolution of local therapies (radiotherapy, surgical and interventional radiology techniques) has contributed to the improvement of survival of patients with advanced sarcoma. In this article, we review the evidence regarding local treatments in advanced sarcoma, as well as its integration with systemic therapies, to provide the reader a wider and deeper perspective on the management of patients with metastatic sarcoma.

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.

[Multimodal treatment of localized high-grade soft tissue sarcomas of the extremities : Summary and discussion of the current S3 guidelines on adult soft tissue sarcomas and the ESMO guidelines on soft tissue and visceral sarcomas]. / Multimodale Therapie der lokalisierten High-grade-Weichgewebesarkome der Extremitäten : Zusammenfassung und Diskussion der aktuellen S3-Leitlinie "Adulte Weichgewebesarkome" und der ESMO-Guideline "Soft tissue and visceral sarcomas".

Soft tissue sarcomas are rare, heterogeneous tumors that are frequently in the extremities. Treatment includes surgical resection, combination chemotherapy and/or radiotherapy, as well as supplementary procedures such as isolated limb perfusion and regional deep hyperthermia. The prognosis depends on the tumor stage and the approximately 70 histological subtypes, with specific treatment approaches existing only for some subtypes. This review summarizes the recommendations of the German S3 guideline "Adult Soft Tissue Sarcomas" and the European Society for Medical Oncology (ESMO) guideline "Soft tissue and visceral sarcomas" regarding the diagnostic workup and therapy of soft tissue sarcomas of the extremities.

KIT and PDGFRA Mutations and Survival of Gastrointestinal Stromal Tumor Patients Treated with Adjuvant Imatinib in a Randomized Trial.

PURPOSE: Limited data are available about the influence of KIT and PDGFRA mutations on overall survival (OS) of patients with gastrointestinal stromal tumor (GIST) treated with adjuvant imatinib. PATIENTS AND METHODS: The Scandinavian Sarcoma Group XVIII/AIO multicenter trial accrued 400 patients with a high risk for GIST recurrence after macroscopically complete surgery between February 4, 2004, and September 29, 2008. The patients received adjuvant imatinib 400 mg/day for either 1 year or 3 years based on random allocation. We analyzed using conventional sequencing KIT and PDGFRA mutations centrally from 341 (85%) patients who had localized, centrally confirmed GIST, and correlated the results with recurrence-free survival (RFS) and OS in exploratory analyses. RESULTS: During a median follow-up time of 10 years, 164 RFS events and 76 deaths occurred. Most patients were re-treated with imatinib when GIST recurred. Patients with KIT exon 11 deletion or indel mutation treated with 3 years of adjuvant imatinib survived longer than patients treated for 1 year [10-year OS 86% versus 64%, respectively; HR, 0.34; 95% confidence interval (CI), 0.15-0.72; P = 0.007], and also had longer RFS (10-year RFS 47% versus 29%; HR, 0.48; 95% CI, 0.31-0.74; P < 0.001). Patients with KIT exon 9 mutation had unfavorable OS regardless of the duration of adjuvant imatinib. CONCLUSIONS: Compared with 1 year of imatinib, 3 years of adjuvant imatinib led to 66% reduction in the estimated risk of death and a high 10-year OS rate in the subset of patients with a KIT exon 11 deletion/indel mutation.

Quality Measurement for Soft Tissue Sarcomas in Germany: First Results of the Certified Sarcoma Centres.

INTRODUCTION: Soft tissue sarcomas (STSs) are rare diseases. A high level of standardization and centralization was lacking in Germany until 2018. METHODS: By developing an evidence-based guideline and a certification system for sarcoma centres, foundations for structured, guideline-based, and centralized sarcoma care were defined. First results of the certified sarcoma centres are presented. RESULTS: The first 3 years of data collection show good results for case volume, presentation rates in pretherapeutic and postoperative tumour boards, psycho-oncological counselling, and study rates. However, other indicators (e.g., preoperative or postoperative radiotherapy for operated high-risk STS without GIST, counselling rates social services) still have potential for improvement. Based on these results, the set of indicators could be further improved. CONCLUSIONS: A sarcoma-specific quality assurance scheme that includes guideline-derived quality indicators was developed. In future, a broader database will allow further insights into sarcoma care in Germany.

Preoperative Hilar and Mediastinal Lymph Node Staging in Patients with Suspected or Diagnosed Lung Cancer: Accuracy of 18F-FDG-PET/CT:A Retrospective Cohort Study of 138 Patients.

The aim of this study was to evaluate the diagnostic accuracy of integrated 18F-fluorodeoxyglucose positron emission computed tomography (18F-FDG-PET/CT) in hilar and mediastinal lymph node (HMLN) staging of suspected or proven lung cancer, and to investigate potential risk factors for false negative and false positive HMLN metastases. We retrospectively analyzed 162 consecutive patients with suspected or pathologically proven non-small cell lung cancer (NSCLC). The receiver operating characteristic (ROC) curve was generated to determine the diagnostic efficacy of 18F-FDG-PET/CT. Univariate and multivariate analyses were conducted to detect risk factors of false positives and false negatives. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of integrated 18F-FDG-PET/CT in detecting HMLN metastases were 59.1% (26/44), 69.1% (65/94), 47.3% (26/55), 78.3% (65/83), and 65.9% (91/138), respectively. The ROC curve showed an area under the curve (AUC) of 0.625 (95%-CI 0.468-0.782). The incidence of false negative and false positive HMLN metastases was 21.7% (18/83) and 52.7% (29/55), respectively. Our data shows that integrated 18F-FDG-PET/CT staging provides lower specificity and sensitivity. This confirms the ESTS guideline on lymph node staging for PET-positive HMLN. Yet it advocates more invasive staging even for PET-negative HMLN.

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.

Imaging Properties and Tumor Targeting of 68Ga-NeoBOMB1, a Gastrin-Releasing Peptide Receptor Antagonist, in GIST Patients.

Background: Gastrin-releasing peptide receptors (GRPRs) are molecular imaging targets in multiple malignancies. Recently, NeoBOMB1, a 68Ga-labelled antagonist to GRPRs, was developed for PET. Here we report the outcome of a Phase I/IIa clinical trial (EudraCT 2016-002053-38) describing diagnostic properties and covariates influencing uptake of 68Ga-NeoBOMB1 in oligometastatic gastrointestinal stromal tumor (GIST) patients. Methods: Nine patients with advanced GIST using PET/CT (computed tomography) were included. After kit-based 68Ga-NeoBOMB1 preparation with a licensed 68Ge/68Ga generator, 3 MBq/kg body weight were injected intravenously. PET/CT included dynamic and static PET scans 5, 12 and 18 min and 1, 2, and 3−4 h post injection (first six patients) and static PET scans 2 and 3−4 h post injection (last three participants). Tumor targeting was assessed on a per-lesion and per-patient basis. Results: Six patients showed visible radiotracer uptake in at least one tumor lesion. Seventeen out of 37 tumor lesions exhibited significant 68Ga-NeoBOMB1 uptake (median SUVmax 11.8 [range 2.8−51.1] 2 h p.i. and 13.2 [range 2.5−53.8] 3−4 h p.i) and improved lesion-to-background contrast over time. Five lesions (13.5%) were identified only by 68Ga-NeoBOMB1-PET, with no correlation on contrast-enhanced CT. Three patients showed no radiotracer accumulation in any lesions. Tracer uptake correlated with male sex (p < 0.0001), higher body mass index (p = 0.007), and non-necrotic lesion appearance (p = 0.018). There was no association with whole-lesion contrast enhancement, hepatic localization, mutational status, or disease duration. Conclusions: 68Ga-NeoBOMB1-PET exhibits variable tumor uptake in advanced-stage GIST patients, correlating with lesion vitality based on CT contrast uptake, opening the possibility of a theragnostic approach in selected cases.

The Therapeutic Role of Plastic and Reconstructive Surgery in the Interdisciplinary Treatment of Soft-Tissue Sarcomas in Germany-Cross-Sectional Results of a Prospective Nationwide Observational Study (PROSa).

Although the involvement of plastic surgery has been deemed important in the treatment of sarcoma patients to avoid oncological compromises and ameliorate patient outcomes, it is not ubiquitously available. The accessibility of defect reconstruction and its therapeutic impact on sarcoma care is the subject of this analysis. Cross-sectional data from 1309 sarcoma patients were collected electronically at 39 German study centers from 2017 to 2019. A total of 621 patients with surgical treatment for non-visceral soft-tissue sarcomas were included. The associated factors were analyzed exploratively using multifactorial logistic regression to identify independent predictors of successful defect reconstruction, as well Chi-squared and Cochran-Mantel-Haenszel tests to evaluate subgroups, including limb-salvage rates in extremity cases. A total of 76 patients received reconstructive surgery, including 52 local/pedicled versus 24 free flaps. Sarcomas with positive margins upon first resection (OR = 2.3, 95%CI = 1.2-4.4) that were excised at centers with lower degrees of specialization (OR = 2.2, 95%CI = 1.2-4.2) were independently associated with the need for post-oncological defect coverage. In this context, the inhouse availability of plastic surgery (OR = 3.0, 95%CI = 1.6-5.5) was the strongest independent predictor for successful flap-based reconstruction, which in turn was associated with significantly higher limb-salvage rates (OR = 1.4, 95%CI = 1.0-2.1) in cases of extremity sarcomas (n = 366, 59%). In conclusion, consistent referral to specialized interdisciplinary sarcoma centers significantly ameliorates patient outcomes by achieving higher rates of complete resections and offering unrestricted access to plastic surgery. The latter in particular proved indispensable for limb salvage through flap-based defect reconstruction after sarcoma resection. In fact, although there remains a scarcity of readily available reconstructive surgery services within the current sarcoma treatment system in Germany, plastic and reconstructive flap transfer was associated with significantly increased limb-salvage rates in our cohort.

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.

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.

Final Safety and Health-Related Quality of LIfe Results of the Phase 2/3 Act.In.Sarc Study With Preoperative NBTXR3 Plus Radiation Therapy Versus Radiation Therapy in Locally Advanced Soft-Tissue Sarcoma.

PURPOSE: Act.In.Sarc (NCT02379845) demonstrated that the first-in-class radioenhancer NBTXR3, activated by preoperative radiation therapy (RT), doubled the rate of pathologic complete response after resection compared with preoperative RT alone in adult patients with locally advanced soft tissue sarcoma of the extremity or trunk wall (16.1% vs 7.9%, P = .045), and more patients achieved R0 resections (77.0% vs 64.0%, P = .042). These are the toxicity and health-related quality of life (HRQoL) results. METHODS AND MATERIALS: Act.In.Sarc randomized eligible patients 1:1 to either NBTXR3 (single intratumoral injection, volume equivalent to 10% of baseline tumor volume, at 53.3 g/L) activated by external-beam RT (arm A) or external-beam RT alone (arm B) (50 Gy in 25 fractions), followed by surgery in both arms. Here, we report the safety analyses in the all-treated population with a long-term follow-up of at least 2 years, and HRQoL in the intention-to-treat full analysis set. RESULTS: During the on-treatment period, serious adverse events (SAEs) of all grades related to NBTXR3 occurred in 10.1% (9/89) of patients (arm A), and SAEs related to RT occurred in 5.6% (5/89) (arm A) versus 5.6% (5/90) (arm B); postsurgery hospitalization owing to SAEs occurred in 15.7% (14/89) (arm A) versus 24.4% (22/90) (arm B). During the follow-up period, posttreatment SAEs (regardless of relationship) occurred in 13.5% (12/89) (arm A) versus 24.4% (22/90) (arm B). NBTXR3 did not negatively affect HRQoL; during the follow-up period, there was an improvement in most mean Toronto extremity salvage, EuroQoL 5-dimension (EQ-5D), EQ5D02-EQ visual analog scale, reintegration to normal living index, and musculoskeletal tumor rating scale scores. CONCLUSIONS: NBTXR3 did not negatively affect safety or HRQoL. Long-term safety results reinforce the favorable benefit-risk ratio of NBTXR3 plus RT.

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.