Desmoid-type Fibromatosis Patients Research Articles

Efficacy and Safety of Auranofin for Progressive Desmoid-Type Fibromatosis: The Study Protocol of an Open-Label Phase II Trial.

Background As desmoid-type fibromatosis (DF) exhibits a high recurrence rate after surgery, initial active surveillance followed by medical therapy is the mainstay of the treatment. However, there are few effective drugs with acceptable side effects. Methodology Among drugs that have been used for a long period and possess a known safety profile, auranofin was observed to be effective in suppressing DF using the drug repositioning method in our laboratory. This clinical study has been designed to examine the efficacy and safety of auranofin, an approved anti-rheumatic drug, in patients with progressive DF. Results This study is conducted as a single-center, single-arm, open-label study. Auranofin 3 mg tablets will be administered twice daily to DF patients with progressive disease. The primary endpoint is progression-free survival at 26 weeks after starting treatment. Secondary endpoints include response rate, T2-weighted MRI evaluation, pain intensity, quality of life (QOL), and safety assessment. Conclusions This is the first clinical trial of auranofin in patients with aggressive DF. The study will allow an in-depth understanding of the efficacy of auranofin for response rate as well as for changes in MRI findings, pain, and QOL in patients with aggressive DF.

Physical symptom burden in patients with desmoid-type fibromatosis and its impact on health-related quality of life and healthcare use.

Desmoid-type fibromatosis (DTF) has a highly variable clinical course with varying intensity of symptoms. The objectives of this study were to identify subgroups of DTF patients based on physical symptom burden and to compare symptom burden subgroups on health-related quality of life (HRQoL) and healthcare use (univariate and multivariate). Desmoid-type fibromatosis patients from the United Kingdom and the Netherlands received cross-sectional questionnaires on HRQoL (EORTC QLQ-C30), DTF-specific HRQoL (DTF-QoL) and healthcare utilisation. Latent class cluster analysis was performed to identify subgroups based on patients' symptom burden using EORTC QLQ-C30 and DTF-QoL physical symptom items. Multivariate linear and logistic regression analyses were conducted to examine associations of symptom burden with HRQoL and healthcare utilisation, respectively. Among 235 DTF patients, four symptom burden clusters were identified, with low symptom burden (24%), intermediate symptom burden-low pain (20%), intermediate symptom burden-high pain (25%) and high symptom burden (31%). DTF patients with high symptom burden had clinically relevant lower HRQoL scores compared to patients with low and intermediate symptom burden (p < 0.001) and reported more general and DTF-related visits to their general practitioner compared to the low symptom burden cluster (p < 0.01). In the multivariate analyses, symptom burden was independently associated with both HRQoL and healthcare utilisation. This study identified four distinct subgroups of DTF patients based on their level of symptom burden, with a considerable number of patients being highly symptomatic. Knowledge of the level of symptom burden DTF patients experience can help to identify patients at risk of poorer outcomes and tailor supportive care to the individual needs of DTF patients.

Efficacy and tolerability of sorafenib in desmoid-type fibromatosis: A need to review dose

BackgroundSorafenib is currently one of the recommended treatments for symptomatic patients with desmoid-type fibromatosis (DTF). In this study, we aim to assess the clinical efficacy and tolerability of sorafenib in DTF patients. MethodologyPatients aged>18 years with a histological diagnosis of DTF and who have received sorafenib were enroled in this prospective observational study. Demographic data, clinical profile, the initial dose of sorafenib, treatment-related toxicities, dose modifications, and responses were recorded. The primary objective was to assess the objective response rate (ORR). The secondary objectives were to evaluate progression-free survival (PFS), tolerability, and adverse effects of sorafenib. Response assessment was based on response evaluation criteria in solid tumours 1.1 criteria. Adverse effects were graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 criteria. Time to event was calculated by Kaplan-Meier analysis, and survival was compared by log-rank test. Univariate and multivariable cox regression analysis were used to find independent predictors of relapse. ResultsA total of 104 patients were enroled in the study. The median age of the study population was 32 (range, 18–81) years, and 66.35% of patients were females. On response assessment, ORR was 46.1% and stable disease was observed in 31.7% patients. ORR was higher in the appendicular site (51.7%) compared to the abdominal site (27.2%). PFS at 1 and 2 years was 86.6% (79.6–92.7%) and 73.7% (62.4–82.8%), respectively. Two-thirds (66.6%) of patients had already received some form of treatment. At the time of analysis, 70 (67.3%) patients were continuing sorafenib. Only 4.8% stopped sorafenib due to progression, 10.5% due to intolerable adverse effects, and 17.3% due to other reasons. The common treatment-related toxicities were hand-foot skin reaction (HFSR) (89.4%), fatigue (79.8%), alopecia (70.1%), and diarrhoea (48.0%). In the patients with a starting dose of ≥400 mg (48.0% of patients), discontinuation was necessitated in 12% of patients, and further dose reduction was required in 58%, while only about 13% required dose reduction or discontinuation at a starting dose of 200 mg (51.9% of patients). Responses were not compromised due to lower starting doses. ConclusionsSorafenib has good activity in DTF, but it is associated with significant toxicity. The adverse effect profile is distinct in Indian patients with higher HFSR and alopecia. Due to the high rate of dose reduction/discontinuation with a starting dose of 400 mg, a starting dose of 200 mg may be recommended in Indian patients.

Health-related quality of life (HRQoL), anxiety, and depression in patients with desmoid type fibromatosis.

Data on the impact of desmoid type fibromatosis (DTF) on emotional distress and health-related quality of life (HRQoL) is sparse. In this prospective cross-sectional study, patients with DTF and healthy controls were asked to fill the EORTC QLQ-C30, GAD-7, and PHQ-9 questionnaires. The objectives were to determine HRQoL, anxiety, and depression in patients with DTF. Two hundred four subjects (102 DTF patients and 102 healthy controls) were recruited. The median age of DTF patients at recruitment into the study was 31years (IQR, 25-37years). There was a female preponderance with a male:female ratio of 1:1.83. Appendicular skeleton and abdomen sites were most commonly involved in 59% and 22.5% respectively. About half (54%) of patients were currently on sorafenib and 41% were under active surveillance. The mean global health status in DTF patients was 65.58 ± 22.64, significantly lower than healthy controls. Similarly, DTF patients scored low on all functional scales except cognitive functioning. The symptom scale showed a significantly higher symptom burden of fatigue, pain, insomnia, and financial difficulties. Anxiety and depression was observed in 39.22% and 50% of DTF patients respectively. DTF patients had higher rates of mild, moderate, and severe anxiety and depression compared to healthy controls. DTF patients have significant symptom burden, poor functioning, and heightened anxiety and depression as compared to healthy controls. HRQoL, anxiety, and depression should be routinely used to assess symptom burden and treatment efficacy in DTF patients.

1511P Efficacy and toxicity of sorafenib in desmoid type fibromatosis: A real-world experience

There is a lack of consensus in management of desmoid type fibromatosis (DTF). Sorafenib is preferred for the management of symptomatic patients. In this study, we aim to assess the clinical efficacy and adverse effects of sorafenib therapy in DTF patients.

Unraveling Desmoid-Type Fibromatosis-Specific Health-Related Quality of Life: Who Is at Risk for Poor Outcomes

Simple SummaryDesmoid-type fibromatosis (DTF) is an uncommon, non-metastasising soft-tissue tumour. Patients can experience a wide variety of disease-specific issues related to the unpredictable clinical course and aggressiveness of DTF, negatively impacting their health-related quality of life (HRQoL). Little is known about which DTF patients are particularly affected by an impaired HRQoL. In the current study, HRQoL was evaluated among different groups of DTF patients, using the EORTC QLQ-C30 and the DTF-QoL, a DTF-specific HRQoL questionnaire. Age, sex, presence of comorbidities, and type of treatment were found to be most strongly associated with DTF-specific HRQoL outcomes. In general, socio-demographic factors had the greatest impact on generic HRQoL, whereas the influence of clinical factors was mainly seen on the DTF-QoL, underlining the importance of a disease-specific questionnaire. Knowledge of the differences in DTF-specific HRQoL between subgroups can be used to individualize the HRQoL-measurement strategy for research and clinical practice.Desmoid-type fibromatosis (DTF) is a rare, soft-tissue tumour. These tumours do not metastasize, but their local aggressive tumour growth and unpredictable behaviour can have a significant impact on health-related quality of life (HRQoL). Little is known about which DTF patients are particularly affected by an impaired HRQoL. The objectives of this study were to assess HRQoL among different groups of DTF patients and to investigate which socio-demographic and clinical characteristics were associated with DTF-specific HRQoL. A cross-sectional study was conducted among DTF patients from the United Kingdom and the Netherlands. HRQoL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30), accompanied by the DTF-QoL to assess DTF-specific HRQoL. The scores were compared amongst subgroups, based on the socio-demographic and clinical characteristics of DTF patients. Multiple linear regression analyses with a backward elimination were conducted to identify the factors associated with DTF-specific HRQoL. A total of 235 DTF patients completed the questionnaires. Female patients, patients with more than two comorbidities, or patients who received treatment other than only active surveillance (AS) or surgery scored significantly worse on the subscales of both the EORTC QLQ-C30 and DTF-QoL. Patients that were ≥ 40 years scored significantly worse on the physical functioning scale of the EORTC QLQ-C30, while younger patients (18–39 years) scored significantly worse on several DTF-QoL subscales. Differences in the DTF-QoL subscales were found for tumour location, time since diagnosis and the presence of recurrent disease. Furthermore, treatments other than AS or surgery only, female sex, younger age and the presence of comorbidities were most frequently associated with worse scores on the DTF-QoL subscales. This study showed that (DTF-specific) HRQoL differs between groups of DTF patients. Awareness of these HRQoL differences could help to provide better, personalised care that is tailored to the needs of a specific subgroup.

Abstract 6168: Beta-catenin and PDGFRB modulate HIF1a in desmoid cells to promote sorafenib-sensitive paracrine signaling pathways

Abstract Introduction: Sorafenib has been shown to have clinical benefit in desmoid-type fibromatosis (DF), a mesenchymal neoplasm associated with activating CTNNB1 mutations. This study sought to better understand the mechanisms of sorafenib activity in DF by defining downstream pathways dysregulated by β-catenin. Methods: Primary DF cell lines (DES9525, 3276, 8163) were developed from surgical specimens and validated by Sanger sequencing of CTNNB1. Gene expression in DF tumors was assessed with U133A arrays and in cell lines using RNA-seq. Lentiviral systems were used to deliver shRNA (or scramble control) and overexpression constructs. Luciferase reporter assay was employed to assess transcription activity. Cell proliferation, protein levels/phosphorylation and gene expression were assessed by CyQuant DNA quantification, immunoblot, and RT-PCR, respectively. Endothelial cell (HUVEC) tube formation was quantitated manually using light microscopy. Results: Gene set enrichment analysis of DES9525 CTNNB1 knock-down (KD) showed decreased expression of genes commonly associated with hypoxia and angiogenesis. Unsupervised clustering confirmed in vivo relevance as expression levels of hypoxia-associated genes clustered 45 DF tumors separately from normal mesenchymal tissue (fat and muscle). Higher baseline levels of HIF1α were observed in DF cell lines compared to mesenchymal stem cells and abrogation of CTNNB1 reduced cellular levels of HIF1α and HIF transcriptional activity. DF co-culture with endothelial cells induced VEGFR phosphorylation on HUVECs and tube formation; HIF1A KD inhibited VEGFR phosphorylation and reduced tube formation &amp;gt;50% but had no effect on desmoid cell proliferation. Similar inhibition was observed after co-culture of DF CTNNB1 KD cells with endothelial cells (&amp;gt;50% reduction in tube formation, p&amp;lt;0.05), but not after overexpression of HIF1A in CTNNB1 KD cells. Sorafenib inhibited this tube-formation (60%, p&amp;lt;0.05) induced by DF at lower concentrations (1μM) as compared to those required to inhibit DF cell proliferation (IC50 10uM). While sorafenib directly inhibited VEGFR phosphorylation on endothelial cells, it also inhibited phosphorylation of PDGFRB and decreased HIF1α levels in DF cells. Exogenous PDGF-BB conversely increased levels of HIF1α in DF cells and endothelial tube formation (2 times, p&amp;lt;0.05) when added to DF but not to endothelial cells grown in the absence of DF cells. Conclusion: β-catenin and PDGFRB signaling modulate cellular levels of HIF1α in DF cells to affect endothelial cells via VEGFR. Sorafenib inhibits a PDGFR/β-catenin/HIF1α axis by modulating signaling pathways both on the DF cells themselves as well as RTK targets of sorafenib on stromal cells. Improved understanding of these interactions may allow for more specific therapeutic selection in DF patients. Citation Format: Jia Hu, Anthony Villano, Rachael Connor, Yuliy Rozenberg, Alankrta Venkatesh, Nicholas Socci, Samuel Singer, Aimee Crago. Beta-catenin and PDGFRB modulate HIF1a in desmoid cells to promote sorafenib-sensitive paracrine signaling pathways [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6168.

A nationwide prospective clinical trial on active surveillance in patients with non-intra-abdominal desmoid-type fibromatosis; the Grafiti trial

Background: Desmoid-type fibromatosis (DTF) has a highly variable clinical course, displaying phases of progressive growth, stabilization or even spontaneous regression without treatment. Active surveillance (AS) is currently recommended as primary treatment. The aim of this study was to assess tumour behaviour and the efficacy of AS in DTF patients.

Development of a Disease-Specific Health-Related Quality of Life Questionnaire (DTF-QoL) for Patients with Desmoid-Type Fibromatosis.

Simple SummaryDesmoid-type fibromatosis (DTF) is an uncommon soft-tissue tumour that is incapable of metastasising. Patients can experience a variety of physical and psychological symptoms, making assessment of health-related quality of life (HRQoL) highly relevant. Measuring the impact of DTF on HRQoL can be challenging due to the rare character and variable clinical presentation of the disease. Therefore, a HRQoL instrument assessing DTF-specific issues is needed. Previously, a provisional DTF-specific HRQoL tool was developed (the DTF-QoL). The aim of the current study was to pre-test the DTF-QoL. Pre-testing of the questionnaire led to the selection of 96 questions, conceptualised into three symptom subscales, eleven disease-impact subscales and six single items, together forming the final DTF-QoL. This questionnaire can be used in both clinical and research settings to evaluate HRQoL of DTF patients, which could help to provide personalised care and improve overall patient experience.Sporadic desmoid-type fibromatosis (DTF) is a rare, non-metastasising soft-tissue tumour. Patients can experience a variety of disease-specific issues related to the unpredictable clinical course and aggressiveness of DTF, which negatively impacts health-related quality of life (HRQoL). These DTF-specific issues are not captured by generic HRQoL tools. A 102-item provisional DTF-specific HRQoL tool, the DTF-QoL, was previously developed. The aim of this study was to pre-test the psychometric properties of the DTF-QoL by administering it together with the EORTC Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) to 236 DTF patients from the United Kingdom and the Netherlands. Construct validity and reliability were determined based on factor analysis, multi-trait scaling analysis, Cronbach’s alpha, and correlations with the EORTC QLQ-C30 scales. Ninety-six items were selected, conceptualised into three symptom scales, eleven disease-impact scales and six single items, together forming the final DTF-QoL. Scaling assumptions were fully or moderately met for ten out of fourteen scales. Cronbach’s alpha ranged from 0.551–0.908. Most scales of the DTF-QoL were weakly or moderately correlated with the EORTC QLQ-C30. The DTF-QoL is a promising tool capturing the whole spectrum of DTF-specific issues. Implementation of the DTF-QoL in research and clinical practice will help to personalise HRQoL measurement and clinical care for DTF patients.

Efficacy and safety of cyclooxygenase 2 inhibitors for desmoid tumor management: a systematic review.

ABSTRACTThe efficacy and safety of cyclooxygenase 2 (COX2) inhibitors for the treatment of desmoid-type fibromatosis (DF) are unclear. Therefore, we systematically reviewed related literature to assess the efficacy and safety of COX2 inhibitors for DF treatment. We searched pertinent literature between January 1999 and August 2017 to identify relevant studies using the keywords “Fibromatosis, aggressive” and “Cyclooxygenase inhibitors.” Thereafter, we screened and determined the quality of the studies using the Grading of Recommendations Assessment, Development, and Evaluation system and extracted the article data. The critical outcomes selected were the efficacy and adverse effects of COX2 inhibitors. Efficacy was evaluated in terms of clinical benefit when patients showed complete response, partial response, and stable disease. Thirty-one articles were identified from the database search, and one was identified through the reviewers’ manual search. Finally, we retrieved six studies, including three case reports, comprising 89 patients after the first and second screenings. Fifty-three patients were excluded because three studies were reported from the same institution; hence, in total, 36 patients were included. Clinical benefit was noted in 64% of the patients. Three adverse effects were identified from the records of the six extracted studies. The strategy of watchful waiting using COX2 inhibitors with few side effects is weakly recommended for DF, especially DF patients with pain.

The Evaluation of Health-Related Quality of Life Issues Experienced by Patients with Desmoid-Type Fibromatosis (The QUALIFIED Study)-A Protocol for an International Cohort Study.

Simple SummaryDesmoid-type fibromatosis (DTF) is an uncommon soft tissue tumour with a high recurrence rate after resection. DTF does not metastasise, but its locally aggressive tumour growth and chronic character can cause significant morbidity. Although overall mortality is low, patients can experience a high symptom burden, making assessment of health-related quality of life (HRQoL) highly relevant. At present, data on HRQoL in DTF patients are limited. The QUALIFIED study aims to (1) pre-test a previously developed DTF-specific HRQoL tool (the DTF-QoL); (2) evaluate prevalence of HRQoL issues in adult DTF patients; and (3) identify subgroups at risk of impaired HRQoL. An international, multicentre, cross-sectional, observational cohort study will be conducted to validate the DTF-specific HRQoL questionnaire and to gain more insight into the issues experienced by DTF patients. This information will help to improve clinical practice, symptom control and patient satisfaction. When validated, the DTF-QoL can be used in both clinical and research settings to evaluate HRQoL of DTF patients.Sporadic desmoid-type fibromatosis (DTF) is a rare soft tissue tumour with an unpredictable clinical course. These tumours are incapable of metastasising, but their local aggressive tumour growth and tendency to recur locally can result in a substantial symptom burden. Measuring the impact of DTF on health-related quality of life (HRQoL) can be challenging due to the variable clinical presentation of the disease. Therefore, a HRQoL instrument assessing DTF-specific issues is needed. The QUALIFIED study aims to (1) pre-test a previously developed DTF-specific HRQoL tool (the DTF-QoL); (2) evaluate prevalence of HRQoL issues in adult DTF patients; and (3) identify subgroups at risk of impaired HRQoL. This study (NCT04289077) is an international, multicentre, cross-sectional, observational cohort study. Patients ≥ 18 years with sporadic DTF from the Netherlands and the United Kingdom will be invited to complete a set of questionnaires specifically composed for this patient group. Questionnaires will be completed using PROFILES (Patient Reported Outcomes Following Initial treatment and Long-term Evaluation of Survivorship). Analyses will include testing the psychometric properties of the DTF-QoL and evaluating the prevalence of HRQoL issues using the DTF-QoL, EORTC QOL-C30 and EQ-5D-5L, among other questionnaires. This study will provide insight into HRQoL issues experienced by patients with DTF. Awareness of these issues and the implementation of the DTF-QoL in research and clinical practice can help to improve overall HRQoL and to provide personalised care.

Magnetic resonance imaging patterns of tumor response to chemotherapy in desmoid-type fibromatosis.

BackgroundWe aimed to investigate changes in volume and MRI T2‐weighted intensity in desmoid‐type fibromatosis (DF) receiving methotrexate plus vinca‐alkaloids (MTX‐VA) at Istituto Nazionale dei Tumori, Milan.MethodsAll cases of sporadic DF treated with MTX‐VA from 1999 to 2019 were reviewed. MRIs at baseline, 6 and 12 months of chemotherapy and at treatment withdrawal were retrospectively reviewed, contouring the tumor lesion and measuring diameters, volume, and mean T2‐signal intensity (normalized to muscle) changes. These parameters were also evaluated according to clinical variables.ResultsThirty‐two DF patients were identified. Best RECIST response was: 25% partial response, 69% stable disease, 6% progression. A ≥65% tumor volume reduction was observed in 38%, <65% reduction in 53%, an increase in 9%. 22% had RECIST stable disease with a ≥65% tumor volume reduction. T2‐signal intensity decreased by ≥50% in 47%, <50% in 41% and increased in 12%. In patients with symptomatic improvement while on therapy and in patients maintaining symptomatic improvement during follow‐up, median T2‐signal intensity showed a reduction along the time points (3.0, 1.9, 1.2, 1.1; 2.9, 2.0, 1.2, 1.2, respectively); in patients without symptomatic improvement and in those clinically progressing during follow‐up, a reduction was not observed. High T2‐signal intensity at baseline was observed in patients showing RECIST progression during follow‐up.ConclusionsIn this series, RECIST detected a lower proportion of responses as compared to volumetric and T2‐signal changes. T2‐signal reduction seemed to better reflect symptomatic improvement. High T2‐signal intensity at baseline was related to a higher proportion of further progression.

Patient reported outcomes in patients with desmoid type fibromatosis.

11574 Background: Desmoid type fibromatosis (DTF) is a rare benign neoplasm with infiltrative growth and high local recurrences. Due to long disease course, unpredictable growth pattern, and low mortality, using only survival outcomes may be inappropriate. In this study we assessed the impact of DTF on health related quality of life (HRQoL). Methods: This was a cross-sectional study done in patients with DTF. The study participants were asked to fill the EORTC QLQ-C30, GAD-7 and PHQ- 9 q uestionnaires to assess HRQoL, anxiety and depression . Outcomes were also compared with healthy controls. Results: 204 subjects (102 DTF patients and 102 healthy controls) were recruited. Study parameters have been summarized in Table. Appendicular skeleton (limbs + girdle) was most commonly involved in 59 % patients and abdominal wall or mesentery was involved in 22.5 %. Patients have received median of 2 lines of therapy. 54 % patients were currently on sorafenib and 41 % were under active surveillance. Mean global health status in DTF patient 65.58 ± 22.64, was significantly lower than healthy controls. Similarly, DTF patients scored low on all functional scales except cognitive functioning. Symptom scale showed significantly higher symptom burden of fatigue, pain, insomnia and financial difficulties. Anxiety &amp; depression was observed in 39.22 % and 50 % of DTF patients respectively. DTF patients had higher rates of mild, moderate and severe anxiety and depression compared to healthy controls. No difference was observed based on site of disease. Conclusions: DTF patients have significant symptom burden, poor functioning, and heightened anxiety and depression. Patient reported outcomes should be routinely used to assess treatment efficacy in DTF patients.[Table: see text]

Desmoid-type fibromatosis: toward a holistic management.

Desmoid-type fibromatosis, a rare locally aggressive fibroblastic proliferation, is a treatment challenge. This review aimed to explore recent data about the management of desmoid-type fibromatosis. New data underline the role of kinases and ɣ-secretase in stimulating cell proliferation and invasiveness in desmoid-type fibromatosis. This explains the proven activity of multikinase inhibitors (sorafenib or pazopanib) in the management of desmoid-type fibromatosis or the emerging role of a ɣ-secretase inhibitor. An international guideline for management was recently published, and this guideline take into account patient point of view. Lastly, recent studies highlight the multidimensional burden of desmoid-type fibromatosis, particularly health-related quality of life (HRQoL). Active surveillance with planned MRI is the first-line management in desmoid-type fibromatosis. A site-specific and stepwise approach should be considered for progressive desmoid-type fibromatosis. Further, a risk-benefit analysis that considers the side effects and long-term sequelae should be conducted before deciding to start any treatment. A less aggressive approach should be considered. Multikinase inhibitors are effective, but their tolerability and side effects should be discussed with the patients. The symptoms and HRQoL should be integrated in decision-making. Desmoid-type fibromatosis patients should be offered support to address their needs supportive care.

MRI T1 Contrast-Enhanced Signal Intensity Is a Prognostic Indicator of Imatinib Therapy in Desmoid-Type Fibromatosis.

ObjectiveTo investigate the efficiency of pre-therapy magnetic resonance imaging (MRI) features in predicting the prognosis of desmoid-type fibromatosis patients treated with imatinib.Materials and MethodsA total of 38 desmoid-type fibromatosis patients treated with imatinib were collected in this retrospective study. The high signal intensity on pre-therapy MRI was evaluated on axial T2 and T1 contrast-enhanced sequences with fat suppression. Cox regression and Kaplan–Meier analyses explored the correlation between clinical or radiographic characteristics and progression-free survival (PFS).ResultsHyperintense T1 contrast enhancement (CE) proportion (≥ 75%) was identified as an independent predictor for PFS. Patients with hyperintense T1 CE proportion <75% demonstrated no progression, while patients with hyperintense T1 CE proportion ≥75% demonstrated a progression rate of 78.4%.ConclusionHyperintense T1 CE proportion in the tumor is a potential predictor of disease progression in patients with desmoid-type fibromatosis treated with imatinib. Hyperintense T1 CE proportion <75% indicates progression-free during treatment.

Anti-Angiogenic Agents in Management of Sarcoma Patients: Overview of Published Trials.

We reviewed all fully published clinical trials assessing anti-angiogenic agents in sarcoma patients (last issue, January 13, 2020). Anti-angiogenic macromolecules (e.g., bevacizumab or ombrabulin) provide disappointing results. Many multikinase inhibitors have been assessed with non-randomized phase II trials with limited samples and without stratification according to histological subtypes, therefore interpretation of such trials is very challenging. On the contrary, pazopanib, regorafenib, and sorafenib have been assessed using double-blind placebo-controlled randomized phase II or phase III trials. Compared to placebo, sorafenib demonstrates activity in desmoid-type fibromatosis patients. Based on results of phase 3 trial, pazopanib had obtained approval for treatment of pretreated non-adipocytic soft tissue sarcoma. Regorafenib is currently assessed in several clinical settings and provides significant improvement of progression-free survival in pre-treated non-adipocytic soft tissue sarcoma and in advanced pretreated osteosarcoma. Multikinase inhibitors are a breakthrough in sarcoma management. Many trials are ongoing. Nevertheless, predictive factors are still missing.

Assessing the Desmoid-Type Fibromatosis Patients' Voice: Comparison of Health-Related Quality of Life Experiences from Patients of Two Countries.

Purpose Desmoid-type fibromatosis (DTF) is a rare, nonmetastasising soft tissue tumour. Symptoms, unpredictable growth, lack of definitive treatments, and the chronic character of the disease can significantly impact health-related quality of life (HRQoL). We aimed at identifying the most important HRQoL issues according to DTF patients in two countries, in order to devise a specific HRQoL questionnaire for this patient group. Methods DTF patients and healthcare providers (HCPs) from the Netherlands and the United Kingdom individually ranked 124 issues regarding diagnosis, treatment, follow-up, recurrence, living with DTF, healthcare, and supportive care experiences, according to their relevance. Descriptive statistics were used to calculate priority scores. Results The most highly ranked issues by patients (n = 29) were issues concerning “tumour growth,” “feeling that there is something in the body that does not belong there,” and “fear of tumour growth into adjacent tissues or organs” with mean (M) scores of 3.0, 2.9, and 2.8, respectively (Likert scale 1–4). British patients scored higher on most issues compared to Dutch patients (M 2.2 vs. M 1.5). HCPs (n = 31) gave higher scores on most issues compared to patients (M 2.3 vs. M 1.8). Conclusion This study identified the most relevant issues for DTF patients, which should be included in a DTF-specific HRQoL questionnaire. Additionally, we identified differences in priority scores between British and Dutch participating patients. Field testing in a large, international cohort is needed to confirm these findings and to devise a comprehensive and specific HRQoL questionnaire for DTF patients.

Desmoid-Type Fibromatosis-Clinical Study of an Uncommon Disease.

Desmoid-type fibromatosis is an uncommon disease which mimics sarcoma but is more locally aggressive but with less metastatic potential than sarcoma. Diagnosis is difficult and treatment protocols have changed to include more non-surgical options as compared with sarcoma. This is a retrospective study of the clinical presentation, imaging findings, treatment given, and outcomes of pathologically proven desmoid-type fibromatosis patients who presented to government medical college Kozhikode.

MRI characteristics predict the efficacy of meloxicam treatment in patients with desmoid-type fibromatosis.

This study aimed to determine the clinical significance of MRI characteristics as a possible predictor of responsiveness to meloxicam treatment in patients with desmoid-type fibromatosis (DF). Additionally, it analysed the correlation between CTNNB1 mutation status and signal intensity of MRI. Forty-six patients consecutively treated with meloxicam composed this study. The low-intensity area (LIA) on T2-weighted MRI was determined. We divided patients into two groups based on the efficacy of meloxicam: a clinical benefit group (CB group, including CR: complete response; PR: partial response; and SD: stable disease) and non-clinical benefit group (NB group, including PD: progressive disease). Correlations of the efficacy with LIA and CTNNB1 mutation status with LIA were investigated. In total, 11, 17 and 18 patients showed PR, SD and PD, respectively. The mean LIA ratio before treatment was significantly higher (P<0.001) in the CB group than in the NB group. For predicting the efficacy, sensitivity was 68%, and specificity was 89% when setting the cut-off value as 20% for LIA. Mean changes in the LIA ratio before and after treatment were significantly higher (P=0.01) in the CB group than in the NB group. Mean LIA ratio before treatment was significantly lower (P<0.001) in the S45F mutation group than in the other mutation group. In multivariate analysis, the LIA ratio before treatment was a significant predictor of responsiveness (P=0.02). MRI characteristics were a useful predictor of the efficacy of meloxicam in DF patients. It may be possible to predict the clinical outcome more accurately when combined with other factors, such as CTNNB1 mutantion status.

Wnt targets genes are not differentially expressed in desmoid tumors bearing different activating β-catenin mutations

IntroductionSporadic desmoid-type fibromatosis (DTF) is a rare soft tissue tumor of mesenchymal origin. It is characterized by local invasive growth and unpredictable growth behavior. Three distinct mutations involving the CTNNB1 (β-catenin) gene have been identified in the vast majority of DTF tumors, which cause activation of the Wnt signaling pathway and impact prognosis. This study examines whether the different CTNNB1 mutants (T41A, S45F) occurring in DTF tumors differentially affect Wnt signaling activity, which might explain the different disease course between DTF patients harboring different CTNNB1 mutations. Materials and methodsReal-time polymerase chain reaction (RT-PCR) on 61 formalin fixed paraffin embedded DTF samples with known CTNNB1 status was used to measure the relative mRNA expression level of Wnt target genes AXIN2, DKK1 and CCND1. Additionally, publicly available mRNA expression data retrieved from the Gene Expression Omnibus of 128 DTF samples were used for an unsupervised cluster analyses based on the expression of a selection of Wnt targets. ResultsNo statistically significant difference in relative expression levels of Wnt target genes AXIN2, DKK1 and CCND1 was identified between either CTNNB1 wild-type, S45F or T41A mutated DTF samples. Moreover, the hierarchical cluster analyses using selected Wnt targets did not discriminate between different CTNNB1 mutation types. ConclusionsNo differences in the expression levels of Wnt target genes were observed between the different CTNNB1 mutation types in DTF tumors. Further studies are needed to decipher the mechanism accounting for the diverse disease courses between DTF patients with different CTNNB1 variants.