[Molecular pathology of lung adenocarcinomas, EGFR T790M resistance mutation study].

Aim: In our institute, we have been testing EGFR T790M resistance mutations since 2019, which is the most common resistance mutation that develops during first-line, second- line EGFR TKI treatment of EGFR mutant lung adenocarcinomas. The importance of this study is that the identification of this mutation will allow the use of an effective third-generation TKI. In this article, we report on studies from January 2022 to August 2024, compared with our results from the 2019-2021 period.

International guidelines for intratumoral and intranodal injection of NBTXR3 nanoparticles in head and neck cancers.

Background: An international multidisciplinary panel of experts aimed to provide consensus guidelines describing the optimal intratumoral and intranodal injection of NBTXR3 hafnium oxide nanoparticles in head and neck squamous cell carcinoma (HNSCC) of the oral cavity, oropharynx, and cervical lymph nodes and to review data concerning safety, feasibility, and procedural aspects of administration.

Methods: The Delphi method was used to determine consensus. A 4-member steering committee and a 10-member monitoring committee wrote and revised the guidelines, divided into eight sections.

A recurrent NTRK1 tyrosine kinase domain mutation pair is characteristic in a subset of dedifferentiated liposarcomas.

Introduction: Dedifferentiated liposarcoma (DDLPS) is a common form of liposarcoma with challenging treatment modalities. Pan-TRK immunopositivity can be often observed without NTRK gene fusion in soft tissue sarcomas with myogenic differentiation. Expression and the role of NTRK in DDLPS are under-studied.

Paclitaxel plus Eftilagimod Alpha, a Soluble LAG-3 Protein, in Metastatic, HR+ Breast Cancer: Results from AIPAC, a Randomized, Placebo Controlled Phase IIb Trial.

Purpose: Eftilagimod alpha (efti), a soluble lymphocyte activation gene (LAG-3) protein and MHC class II agonist, enhances innate and adaptive immunity. Active Immunotherapy PAClitaxel (AIPAC) evaluated safety and efficacy of efti plus paclitaxel in patients with predominantly endocrine-resistant, hormone receptor-positive, HER2-negative metastatic breast cancer (ET-resistant HR+ HER2- MBC).

Patients And Methods: Women with HR+ HER2- MBC were randomized 1:1 to weekly intravenous paclitaxel (80 mg/m2) and subcutaneous efti (30 mg) or placebo every 2 weeks for six 4-week cycles, then monthly subcutaneous efti (30 mg) or placebo maintenance.

Trifluridine-Tipiracil and Bevacizumab in Refractory Metastatic Colorectal Cancer.

Background: In a previous phase 3 trial, treatment with trifluridine-tipiracil (FTD-TPI) prolonged overall survival among patients with metastatic colorectal cancer. Preliminary data from single-group and randomized phase 2 trials suggest that treatment with FTD-TPI in addition to bevacizumab has the potential to extend survival.

Methods: We randomly assigned, in a 1:1 ratio, adult patients who had received no more than two previous chemotherapy regimens for the treatment of advanced colorectal cancer to receive FTD-TPI plus bevacizumab (combination group) or FTD-TPI alone (FTD-TPI group).

[Body compositions characteristic in male manual workers: age as a central factor].

Introduction: Morbidity and mortality statistics show a shift in the morbidity structure in Hungary. Those diseases have become increasingly common that are related to lifestyle. Detecting health risk factors across different age, gender and other groups is therefore a priority.

FORT-1: Phase II/III Study of Rogaratinib Versus Chemotherapy in Patients With Locally Advanced or Metastatic Urothelial Carcinoma Selected Based on / mRNA Expression.

Purpose: Rogaratinib, an oral pan-fibroblast growth factor receptor (FGFR1-4) inhibitor, showed promising phase I efficacy and safety in patients with advanced urothelial carcinoma (UC) with mRNA overexpression. We assessed rogaratinib efficacy and safety versus chemotherapy in patients with mRNA-positive advanced/metastatic UC previously treated with platinum chemotherapy.

Methods: FORT-1 (ClinicalTrials.

The Activation of PDGFRβ on Mononuclear Stromal/Tumor Cells in Giant Cell Tumor of Bone After Denosumab Treatment. An Immunohistochemical Study of Five Cases.

Due to the relatively high recurrence rate and the destructive nature of the tumor, the treatment of giant cell tumor is still a challenge. Denosumab appeared to be a promising candidate as a therapeutic drug. However, several studies have reported that tumors can recur during/after treatment with denosumab.

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.

Exploratory analysis of tumor imaging in a Phase 2 trial with cabozantinib in gastrointestinal stromal tumor: lessons learned from study EORTC STBSG 1317 'CaboGIST'.

Background: Gastrointestinal stromal tumors (GISTs) are malignant mesenchymal tumors arising in the gastrointestinal tract. Their systemic treatment is based on the use of tyrosine kinase inhibitors (TKIs) with imatinib, sunitinib, and regorafenib being the preferred agents. Assessment of tumor response to TKI treatment in GISTs is traditionally done according the Response Evaluation Criteria in Solid Tumors (RECIST), while Choi criteria have also been proposed as alternative tool assessing both volumetric and density changes on computer tomography (CT) scans.

[Not Available].

Tumor agnostic therapies target specific genomic alterations regardless of tumor localization and histological subtype. Neurotrophic tropomyosin receptor tyrosine kinase (NTRK) gene fusions are important driver gene targets in both pediatric and adult tumors. The first generation TRK inhibitors provide a rapid, effective, and long-lasting antitumor effect with a favorable side effect profile through selective inhibition of TRK fusion proteins.

Trifluridine/tipiracil in combination with oxaliplatin and either bevacizumab or nivolumab in metastatic colorectal cancer: a dose-expansion, phase I study.

Background: In preclinical studies trifluridine/tipiracil (FTD/TPI) plus oxaliplatin (Industriestrasse, Holzkirchen, Germany) sensitised microsatellite stable (MSS) metastatic colorectal cancer (mCRC) to anti-programmed cell death protein-1; the addition of oxaliplatin or bevacizumab (F Hoffmann- la ROCHE AG, Kaiseraugst, Switzerland) enhanced the antitumour effects of FTD/TPI. This study aimed to investigate the safety and efficacy of FTD/TPI plus oxaliplatin and either bevacizumab or nivolumab (Uxbridge business Park, Uxbridge, United Kingdom) in patients with mCRC who had progressed after at least one prior line of treatment.

Patients And Methods: In 14-day cycles, patients received FTD/TPI 35 mg/m (twice daily, days 1-5) plus oxaliplatin 85 mg/m (day 1), and, on day 1, either bevacizumab 5 mg/kg (cohort A) or nivolumab 3 mg/kg (cohort B).

Lurbinectedin versus pegylated liposomal doxorubicin or topotecan in patients with platinum-resistant ovarian cancer: A multicenter, randomized, controlled, open-label phase 3 study (CORAIL).

Objective: The randomized phase 3 CORAIL trial evaluated whether lurbinectedin improved progression-free survival (PFS) compared to pegylated liposomal doxorubicin (PLD) or topotecan in patients with platinum-resistant ovarian cancer.

Methods: Patients were randomly assigned (1:1) to lurbinectedin 3.2 mg/m 1-h i.

[Novel targeted therapeutic option in oncology: tropomyosin receptor tyrosine kinase inhibitors].

Összefoglaló. A molekuláris diagnosztikai módszerek folyamatos fejlődésének köszönhetően egyre több onkogén genetikai eltérést azonosítanak. A neurotrofikus tropomiozin receptor-tirozin-kináz (NTRK-) génfúziók fontos precíziós onkológiai célpontok, melyek mindhárom NTRK-génben előfordulhatnak, onkogén-hajtóerőként viselkednek.

[EGFR protein is a negative prognostic and predictive factor in wild-type RAS colorectal cancer].

Negative predictive markers of the anti-EGFR antibody therapies are RAS or BRAF mutations, while left sidedness can be considered as a positive predictor. Here we analyzed 97 wild type RAS metastatic colorectal cancers looking for the prognostic and predictive roles of EGFR protein expression. We found that right-sided colorectal cancers are characterized by significantly higher EGFR protein expression as compared to left-sided ones, irrespective of the primary or metastatic tissue analysis.

Complete pathological response to neoadjuvant treatment is associated with better survival outcomes in patients with soft tissue sarcoma: Results of a retrospective multicenter study.

Background: Locally advanced soft tissue sarcoma (STS) management may include neoadjuvant or adjuvant treatment by radiotherapy (RT), chemotherapy (CT) or chemoradiotherapy (CRT) followed by wide surgical excision. While pathological complete response (pCR) to preoperative treatment is prognostic for survival in osteosarcomas, its significance for STS is unclear. We aimed to evaluate the prognostic significance of pCR to pre-operative treatment on 3-year disease-free survival (3y-DFS) in STS patients.

Alpelisib plus fulvestrant for PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer: final overall survival results from SOLAR-1.

Background: Activation of the phosphatidylinositol-3-kinase (PI3K) pathway via PIK3CA mutations occurs in 28%-46% of hormone receptor-positive (HR+), human epidermal growth factor receptor-2-negative (HER2-) advanced breast cancers (ABCs) and is associated with poor prognosis. The SOLAR-1 trial showed that the addition of alpelisib to fulvestrant treatment provided statistically significant and clinically meaningful progression-free survival (PFS) benefit in PIK3CA-mutated, HR+, HER2- ABC.

Patients And Methods: Men and postmenopausal women with HR+, HER2- ABC whose disease progressed on or after aromatase inhibitor (AI) were randomized 1 : 1 to receive alpelisib (300 mg/day) plus fulvestrant (500 mg every 28 days and once on day 15) or placebo plus fulvestrant.

Epileptic Seizure Provoked by Bone Metastasis of Chronic Lymphoid Leukemia and Merkel Cell Carcinoma.

Background: Merkel cell carcinoma (MCC) is a rare primary neuroendocrine cutaneous tumor, rarely metastasizing to the brain. Chronic lymphoid leukemia (CLL) is a disease predisposing to MCC. According to previous reports, headache and focal neurological deficits suggest disease progression to the brain.

Phase I study assessing the mass balance, pharmacokinetics, and excretion of [C]-pevonedistat, a NEDD8-activating enzyme inhibitor in patients with advanced solid tumors.

Pevonedistat (TAK-924/MLN4924) is an investigational small-molecule inhibitor of the NEDD8-activating enzyme that has demonstrated preclinical and clinical activity across solid tumors and hematological malignancies. Here we report the results of a phase I trial characterizing the mass balance, pharmacokinetics, and clearance pathways of [C]-pevonedistat in patients with advanced solid tumors (NCT03057366). In part A (n = 8), patients received a single 1-h intravenous infusion of [C]-pevonedistat 25 mg/m.

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.

Effect of Doxorubicin Plus Olaratumab vs Doxorubicin Plus Placebo on Survival in Patients With Advanced Soft Tissue Sarcomas: The ANNOUNCE Randomized Clinical Trial.

Importance: Patients with advanced soft tissue sarcoma (STS) have a median overall survival of less than 2 years. In a phase 2 study, an overall survival benefit in this population was observed with the addition of olaratumab to doxorubicin over doxorubicin alone.

Objective: To determine the efficacy of doxorubicin plus olaratumab in patients with advanced/metastatic STS.

[Hereditary cancer predisposition syndromes associated with sarcomas].

Based on our current knowledge, 5-10% of all malignancies are part of hereditary cancer syndromes. Although the increasing diagnostic role of molecular genetic testing makes us able to recognize more hereditary cancer patients, the careful exploration of family and clinical history by physicians is still the most important step for the diagnosis. In our review we deal with mesenchymal tumours associated with hereditary syndromes.

EGFR Protein Expression in KRAS Wild-Type Metastatic Colorectal Cancer Is Another Negative Predictive Factor of the Cetuximab Therapy.

The selection of colorectal cancer patients for anti-epidermal growth factor receptor (EGFR) antibody therapy is based on the determination of their RAS mutation status-a strongly negative predictive factor-since the protein target, EGFR, is not a reliable predictor of therapeutic response. In this study, we revisited the EGFR protein issue using a cohort of 90 patients with KRAS exon2 wild-type colorectal cancer who have been treated with cetuximab therapy. Twenty-nine of these patients had metastatic tissue available for analysis.