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.

Quality of life of GIST patients with and without current tyrosine kinase inhibitor treatment: Cross-sectional results of a German multicentre observational study (PROSa).

OBJECTIVE: We investigated the health-related quality of life (HRQoL) of patients with gastrointestinal stromal tumours (GIST). METHODS: In the multicentre PROSa study, the HRQoL of adult GIST patients was assessed between 2017 and 2019 using the European Organisation for Research and Treatment of Cancer HRQoL questionnaire (EORTC QLQ-C30). We performed group comparisons and multivariate linear regressions. RESULTS: Among 130 patients from 13 centres, the mean global HRQoL was 63.3 out of 100 points. Higher sores indicate better HRQoL. The highest restrictions were in emotional, social, role functioning, insomnia, fatigue, and pain. In multivariate linear regression, we found no significant differences between patients receiving tyrosine kinase inhibitor (TKI) treatment and those without TKI treatment as well as between patients treated with curative or with palliative intent. Patients who received multiple lines of TKI treatment had the most restrictions, notably in physical (unstandardized regression coefficient [B] = -15.7), role (B = -25.7), social (B = -18.4), and cognitive functioning (B = -19.7); fatigue (B = 15.93); general health (B = -14.23); and EORTC-sum score (B = -13.82) compared to all other patients. CONCLUSION: The highest HRQoL restrictions were in GIST patients receiving multiple lines of TKI therapy. Underlying causes need further investigation.

Prognosis of Patients with Metastatic Soft Tissue Sarcoma: Advances in Recent Years.

OBJECTIVE: The objective of this study was to investigate the prognosis of patients with metastatic soft tissue sarcomas (STS) and to define prognostic indicators for overall survival (OS). METHODS: All patients who were treated at the Sarcoma Unit at the Mannheim University Medical Center between 2010 and 2016 and who developed metastatic disease deriving from a STS were included in this retrospective analysis. OS was investigated using data from clinical records and German registry offices. Clinical and pathological characteristics were recorded and analyzed. RESULTS: A total number of 212 patients developed metastatic disease from STS during that period. Median OS after first documentation of metastatic disease was 24 months (95% CI 21-33). 1-, 2-, and 5-year OS rates were 70.0% (95% CI 64-77), 49.9% (95% CI 43-58), and 24.8% (95% CI 19-33), respectively. In multivariate analysis, significant predictors for mortality appeared to be gender, age, location and size of the primary tumor, histology, and disease-free interval. CONCLUSION: Being treated in a high-volume STS reference center in Germany, patients with metastatic disease could demonstrate an increased OS compared to former analyses. These data can be used as a benchmark for upcoming studies and highlight that further research on treatment strategies in this rare disease is urgently needed.

Activity and safety of the multi-target tyrosine kinase inhibitor cabozantinib in patients with metastatic gastrointestinal stromal tumour after treatment with imatinib and sunitinib: European Organisation for Research and Treatment of Cancer phase II trial 1317 'CaboGIST'.

BACKGROUND: Gastrointestinal stromal tumour (GIST) is commonly treated with tyrosine kinase inhibitors (TKIs), but most patients ultimately develop secondary resistance. Cabozantinib, a multi-targeted TKI inhibitor, has activity in patient-derived GIST mouse xenograft models and can overcome compensatory MET signalling occurring on TKI treatment. European Organisation for Treatment of Cancer (EORTC) 1317 'CaboGIST' assessed the safety and activity of cabozantinib in patients with GIST who had progressed on imatinib and sunitinib. METHODS: In this multi-center, open label, single arm phase II study, eligible GIST patients received oral cabozantinib (60 mg) once daily. Primary end-point was the progression-free survival rate at 12 weeks assessed by the local investigator per Response Evaluation Criteria in Solid Tumours 1·1. If at least 21 of the first 41 eligible and evaluable patients were progression-free at week 12, the activity of cabozantinib was sufficient to warrant further exploration according to the A'Hern one-stage study design. FINDINGS: A total of 50 eligible patients started treatment between 02/2017 and 08/2018, including four (8%) still continuing cabozantinib at clinical cut-off (09/2019). The number of 3-weekly treatment cycles ranged from 1 to 30. Among the first 41 eligible and evaluable patients, 24 were progression-free at week 12 (58·5%, 95% confidence interval [CI] 42·0-74·0%). Among all 50 patients, 30 were progression-free at week 12 (60%, 95% CI 45-74%). Seven patients achieved a partial response (14%, 95% CI 6-27%), and 34 had stable disease (68%, 95% CI 53-80%) as best response. Progression was seen in eight patients (16%, 95% CI 7-29%), and one was not evaluable. Disease control was achieved in 41 patients (82%, 95% CI 69-91%). Median progression-free survival was 5·5 months (95% CI 3·6-6·9). The most common adverse events were diarrhoea (76%), palmar-plantar erythrodysesthesia syndrome (60%), fatigue (50%), hypertension (42%), weight loss (40%) and oral mucositis (30%), with 32 (64%) patients requiring dose reductions, 27 (54%) having treatment interruptions and no cabozantinib-related deaths observed. INTERPRETATION: EORTC 1317 met its primary end-point, with 24/41 patients being progression-free at week 12 of treatment. The objective response was 14% with an encouraging disease control rate of 82%. Results of this trial confirm preclinical findings and warrant further exploration of cabozantinib in GIST. CLINICAL TRIAL NUMBERS: EORTC 1317, NCT02216578, EudraCT 2014-000501-13.

Clinical Presentation of Gastrointestinal Stromal Tumors.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. They constitute 1-2% of all gastrointestinal neoplasms but are the most common subtype of soft tissue sarcomas, accounting for 20-25%. In the late 1990s, GISTs were more and more recognized as a particular tumor entity. The tumors are supposed to originate from the interstitial pacemaker cells of Cajal. They are usually well circumscribed and can be located in every part of the tubular gastrointestinal tract. Most often GISTs occur in the stomach, followed by the small bowel and colon/rectum. In contrast to epithelial tumors, GISTs grow transmurally and submucosal. GISTs can be found with highly variable growth features including tumors with intraluminal, intra- or transmural, and pedunculated appearance. Here we describe the most common clinical presentation of GISTs on the basis of our 809 patients managed from 2004 to 2017. The median age of our patients was 59 years and the average size of GIST was 75 mm (range: 4 mm to 35 cm). The clinical presentation is very heterogeneous, depending on tumor site, size, and growth pattern. GISTs of the stomach is the group with the lowest rate of acute or emergency symptoms with 31%, followed by GISTs of the duodenum with 42%, whereas GISTs of the small bowel show acute symptoms in more than 50% of the cases and have an emergency surgery rate of almost 15%. Many patients are diagnosed accidentally, through screening examinations, or with latent, unspecific symptoms.

Preserving quality of life as a key treatment goal in advanced soft tissue sarcomas.

INTRODUCTION: Health-related quality of life (HRQoL) is a patient-reported outcome that addresses patients' perceptions of symptoms across physical, emotional, cognitive and social domains. As HRQoL is currently rarely measured outside clinical trials in oncology, it must be inferred from patients' everyday performance during treatment. To gain insight into the HRQoL of advanced STS patients receiving palliative treatment in clinical practice, three case studies of patients treated with trabectedin are examined. Areas covered: The patient in Case 1 has maintained complete remission for more than 8 years after receiving nine cycles of second-line trabectedin followed by secondary surgery for recurrent myxoid liposarcoma, and was able to resume normal activities during trabectedin treatment. Case 2 describes 10 years' follow-up of a patient with myxoid liposarcoma who remains well after many lines of chemotherapy including extended use of trabectedin in the second line. The third case illustrates the feasibility of extending survival time in an elderly patient with metastatic leiomyosarcoma who was able to maintain a busy and active lifestyle while receiving second-line trabectedin. Expert commentary: Owing to its relatively benign safety profile, trabectedin frequently permits prolonged therapy and is generally well tolerated, often allowing patients to carry on with normal daily activities.

Primary and secondary angiosarcomas: a comparative single-center analysis.

BACKGROUND: Angiosarcomas (AS) are rare vascular malignancies. They are subdivided into primary (PAS) and secondary angiosarcomas (SAS). The objective was to compare the characteristics of AS subtypes. METHODS: Eighteen PAS and ten SAS patients treated at our institution between 2004 and 2012 were included in this study. RESULTS: Median age of PAS and SAS patients was 52.9 and 64.2 years, respectively (p = 0.1448). The percentage of women was 27.8% for PAS, but 80.0% for SAS (p = 0.0163). While PAS occurred throughout the body, the majority of SAS arose from the breast (p = 0.0012). All SAS were radiation-induced with a median latency of 7.7 years. The majority of patients with PAS and SAS underwent surgery as primary or recurrence treatment (p > 0.95). Local recurrence was developed by 27.8% of PAS and 50.0% of SAS (p = 0.4119). 61.1% of PAS metastasized, but only 40.0% of SAS (p = 0.4328). Median overall survival for PAS and SAS was 19 and 57 months, respectively (p = 0.2306). CONCLUSION: Radical surgery remains the mainstay of both primary and recurrence treatment. SAS show a high local recurrence rate, while PAS tend towards developing early metastases. Overall, prognosis is poor for both groups.