Familial adenomatosis polyposis-related desmoid tumours treated with low-dose chemotherapy: Results from an international, multi-institutional, retrospective analysis

[Introduction] Desmoid tumour (DT) is a locally aggressive fibroblastic proliferative disease representing the most common extraintestinal manifestation of familial adenomatosis polyposis (FAP). As data on the activity of chemotherapy in these patients are limited, we examined the outcomes of patients treated with low-dose methotrexate (MTX)+vinca alkaloids (vinorelbine or vinblastine).

Adjuvant Imatinib in Patients with GIST Harboring Exon 9 KIT Mutations : Results from a Multi-institutional European Retrospective Study

[Purpose] The effect of high-dose imatinib (800 mg/day) on survival in the adjuvant treatment of patients with resected KIT exon 9–mutated gastrointestinal stromal tumors (GIST) is not established. Here, the association of dose and other clinicopathologic variables with survival was evaluated in a large multi-institutional European cohort.

S3-Leitlinie "Diagnostik, Therapie und Nachsorge des Melanoms" - Kurzfassung

A Phase 2 Trial of Ixabepilone in Asian Patients with Advanced Gastric Cancer Previously Treated with Fluoropyrimidine-Based Chemotherapy

ABSTRACT Background The highest rates of gastric cancer occur in Eastern Asia. Fluoropyrimidine-based therapy is used initially in unresectable and metastatic disease, following progression, 60–70% of patients in Asian countries subsequently receive second-line chemotherapy. However, there is no standard treatment in this setting. Ixabepilone, an epothilone B analog, is a non-taxane microtubule-stabilizing agent with clinical anti-tumor activity across multiple tumor types. We evaluated the efficacy and safety of single-agent ixabepilone as a second-line chemotherapy in Asian patients. Methods Asian patients with unresectable or metastatic gastric adenocarcinoma who had failed previous fluo…

Guidelines for time-to-event end point definitions in sarcomas and gastrointestinal stromal tumors (GIST) trials: results of the DATECAN initiative (Definition for the Assessment of Time-to-event Endpoints in CANcer trials)

ABSTRACT The DATECAN initiative (Definition for the Assessment of Time-to-event Endpoints in CANcer trials) aims to provide recommendations for definitions of time-to-event end points in cancer randomized controlled trials. We relied on a consensus method based on a multidisciplinary panel of experts to develop these guidelines for trials on sarcomas and gastrointestinal stromal tumors. Background The use of potential surrogate end points for overall survival, such as disease-free survival (DFS) or time-to-treatment failure (TTF) is increasingly common in randomized controlled trials (RCTs) in cancer. However, the definition of time-to-event (TTE) end points is rarely precise and lacks unif…

Randomized Phase 3 Trial of Regorafenib in Patients (Patients) with Metastatic and/or Unresectable Gastrointestinal Stromal Tumor (GIST) Progressing Despite Prior Treatment with at Least Imatinib (IM) and Sunitinib (SU) : Grid Trial

LBA10008 Background: Oral multikinase inhibitor regorafenib (REG) demonstrated substantial activity in a phase II trial in pts with GIST after failure of both IM and SU (J Clin Oncol. 2011; 29:606s; abstr 10007). This phase III, randomized, double-blind, placebo-controlled trial evaluated the efficacy and safety of REG for this unmet clinical need. Methods: Eligible pts had metastatic and/or unresectable GIST, objective failure of both prior IM and SU (progressive disease [PD] on, or intolerance to, IM and PD on SU), ≥1 measurable lesion, ECOG performance status 0 or 1. Pts were randomized 2:1 to receive best supportive care plus either REG 160 mg po once daily (3 wks on/1 wk off) or placeb…

Results from a phase III trial (GRID) evaluating regorafenib (REG) in metastatic gastrointestinal stromal tumour (GIST): Subgroup analysis of outcomes based on pretreatment characteristics

10551 Background: REG, an oral receptor kinase inhibitor with activity against KIT, PDGFR, VEGFR, FGFRs, and other oncologic targets, demonstrated significant improvement in progression-free survival (PFS) over placebo (PL) in a phase III study (GRID) of patients (pts) with advanced GIST following failure of at least imatinib (IM) and sunitinib (SU). To understand the impact of pts’ baseline characteristics on outcome, we performed an exploratory analysis of REG effects across pt subgroups based on sex, age, and mitotic index of primary GIST tissue, as well as duration and number of lines of previous therapies. Methods: Adult pts with metastatic GIST (n=199) progressing after at least IM a…

Comprehensive Genomic and Transcriptomic Analysis for Guiding Therapeutic Decisions in Patients with Rare Cancers

Abstract The clinical relevance of comprehensive molecular analysis in rare cancers is not established. We analyzed the molecular profiles and clinical outcomes of 1,310 patients (rare cancers, 75.5%) enrolled in a prospective observational study by the German Cancer Consortium that applies whole-genome/exome and RNA sequencing to inform the care of adults with incurable cancers. On the basis of 472 single and six composite biomarkers, a cross-institutional molecular tumor board provided evidence-based management recommendations, including diagnostic reevaluation, genetic counseling, and experimental treatment, in 88% of cases. Recommended therapies were administered in 362 of 1,138 patient…

Accuracy and Safety of Ultrasound-Guided Core Needle Biopsy of Soft Tissue Tumors in an Outpatient Setting: A Sarcoma Center Analysis of 392 Consecutive Patients.

Simple Summary In patients with unclear soft tissue lesions, treatment planning largely depends on histology. Core needle biopsy is the diagnostic standard in these cases. The aim of this retrospective study was to investigate accuracy and safety of ultrasound guided core needle biopsy at a tertiary referral center. We show that ultrasound guided biopsy was feasible as a one stop shop procedure in an outpatient setting in 87.6% of the cases. The rate of conclusive biopsies was 88.5%. After surgical resection, the dignity, tumor type and histopathological grading of the biopsy matched one of the resection specimens in 97.2%, 92.7% and 92.5% of the cases, respectively. Major complications occ…

cFLIPoverexpression in T cells in thymoma‐associated myasthenia gravis

OBJECTIVE: The capacity of thymomas to generate mature CD4+ effector T cells from immature precursors inside the tumor and export them to the blood is associated with thymoma-associated myasthenia gravis (TAMG). Why TAMG(+) thymomas generate and export more mature CD4+ T cells than MG(-) thymomas is unknown. METHODS: Unfixed thymoma tissue, thymocytes derived thereof, peripheral blood mononuclear cells (PBMCs), T-cell subsets and B cells were analysed using qRT-PCR and western blotting. Survival of PBMCs was measured by MTT assay. FAS-mediated apoptosis in PBMCs was quantified by flow cytometry. NF-κB in PBMCs was inhibited by the NF-κB-Inhibitor, EF24 prior to FAS-Ligand (FASLG) treatment …

Mutational analysis of plasma DNA from patients (pts) in the phase III GRID study of regorafenib (REC) versus placebo (PL) in tyrosine kinase inhibitor (TKI)-refractory GIST: Correlating genotype with clinical outcomes

10503 Background: The phase III GRID study showed that REG provides a significant improvement in progression-free survival (PFS) compared with PL in pts with advanced gastrointestinal stromal tumors (GIST) following failure of at least imatinib (IM) and sunitinib (SU; HR 0.27, p<0.0001). Determining GIST genotype in TKI-refractory disease has proven challenging due to inter-tumoral heterogeneity and pt preference to avoid serial biopsies. To overcome this, we analysed circulating DNA in plasma as a source of tumor DNA and studied the correlation between mutational status and clinical outcome. Methods: DNA was isolated from both archival tumor tissue (n=102) and plasma at baseline (n=163…

Malignant Melanoma S3-Guideline “Diagnosis, Therapy and Follow-up of Melanoma”

This first German evidence-based guideline for cutaneous melanoma was developed under the auspices of the German Dermatological Society (DDG) and the Dermatologic Cooperative Oncology Group (DeCOG) and funded by the German Guideline Program in Oncology. The recommendations are based on a systematic literature search, and on the consensus of 32 medical societies, working groups and patient representatives. This guideline contains recommendations concerning diagnosis, therapy and follow-up of melanoma. The diagnosis of primary melanoma based on clinical features and dermoscopic criteria. It is confirmed by histopathologic examination after complete excision with a small margin. For the stagin…

Pulmonary metastasectomy in soft tissue sarcomas: a systematic review

Background Soft tissue sarcoma (STS) tend to metastasis to the lungs. Pulmonary metastasectomy seems to be a common practice always when plausible. The objective of this article was to review systematically the results of a literature search on pulmonary metastasectomy for STSs published in the last ten years and to offer a brief overview about the current practice as well. Methods Eight retrospective studies published in the period 2010-2020, which included patients with pulmonary metastases and metastasectomy were selected. Indication for surgery, survival rate and factors influencing survival were the primary outcomes, while further interesting findings in the studies were also collected…

FAP-related desmoid tumours treated with low dose chemotherapy: Results from a multicentre retrospective analysis.

11556Background: Desmoid tumours (DTs) are monoclonal neoplasms with fibroblastic-myofibroblastic differentiation and they represent the most common extra-intestinal manifestation of familial adeno...

The Autoimmune Regulator AIRE in Thymoma Biology: Autoimmunity and Beyond

Thymomas are tumors of thymic epithelial cells. They associate more often than any other human tumors with various autoimmune diseases; myasthenia gravis is the commonest, occurring in 10-50% of thymoma patients, depending on the World Health Organization-defined histologic subtype. Most thymomas generate many polyclonal maturing T lymphocytes but in disorganized microenvironments Failure to induce self-tolerance may be a key factor leading to the export of potentially autoreactive CD4 progeny, thus predisposing to autoimmune diseases. Normally, the master Autoimmune Regulator promotes expression of peripheral tissue-restricted antigens such as insulin by medullary thymic epithelial cells a…

Abstract LB-295: Detection of oncogenic kinase mutations in circulating plasma DNA and correlation with clinical benefit in the phase III GRID study of regorafenib vs placebo in TKI-refractory metastatic GIST.

Abstract Background: GRID is a phase III study for patients with advanced gastrointestinal stromal tumors (GIST) following failure of imatinib (I) and sunitinib (S) who were randomized to receive either the multikinase inhibitor regorafenib (R) or placebo (P). R demonstrated a highly significant improvement in progression-free survival compared with P (HR 0.27, p<0.0001). A preplanned retrospective biomarker analysis was conducted to assess GIST genotypes in GRID patients and to explore the possible impact of different driver oncogene mutations on clinical outcomes. Methods: DNA was isolated from archival tumor tissue and analyzed for KIT mutations via Sanger sequencing. The expectat…

Role of adjuvant imatinib dose in radically resected GIST harboring KIT exon 9 mutations

11533 Background: Gastrointestinal stromal tumors (GIST) with a driver mutation in KIT exon 9 (Ex9) represent about 10% of all newly diagnosed cases. In the metastatic setting, Ex9-mutated GIST patients benefit from higher doses of imatinib (800 mg/day vs standard 400 mg/day). The additional therapeutic benefit from a higher dose of imatinib in the adjuvant setting in this molecular subgroup has not been confirmed. Methods: We retrospectively identified 105 patients (pts) with resected Ex9-mutated GIST treated with adjuvant imatinib (800 mg/day or 400 mg/day) in 15 different European centers. Disease-Free Survival (DFS) and Imatinib Failure-Free Survival (IFFS) were calculated and analyzed…