Austrian treatment algorithms in HER2-positive metastatic breast cancer: a 2022 update.

In the past 12 months a plethora of relevant novel data for the treatment of metastatic HER2 positive breast cancer were published. To bring this new evidence into a clinical perspective, a group of Austrian breast cancer specialists updated their previously published treatment algorithm for those patients. For this consensus paper a total of eight scenarios were developed in which treatment strategies appropriate for specific patient profiles were evaluated.

Tissue distribution of epirubicin after severe extravasation in humans.

Purpose: As critical parameter after extravasation of cytotoxic vesicants, anthracyclines were determined in removed tissue from patients requiring surgical intervention due to tissue necrosis. We monitored their distribution within the affected lesion to establish a possible dose-toxicity relation.

Methods: From six patients scheduled for surgery, removed tissue flaps were systematically analysed by HPLC (epirubicin: 5 subjects; doxorubicin: 1 subject).

• Pancho trial (p53-adapted neoadjuvant chemotherapy for resectable esophageal cancer) completed-mutation rate of the marker higher than expected.

Background: In operable esophageal cancer patients, neoadjuvant therapy benefits only those who respond to the treatment. The • Pancho trial represents the first prospective randomized trial evaluating the relevance of the mark53 status for predicting the effect of two different neoadjuvant chemotherapies.

Method: Biomarker analysis was conducted using the mark53 analysis.

Extravasation emergencies: state-of-the-art management and progress in clinical research.

In cancer treatment, extravasation is defined as an inadvertent instillation or leakage of cytotoxic drugs into the perivascular space during infusion. As a dreaded complication of chemotherapy, extravasation has gained increasing attention in recent years. Classified according to their subcutaneous toxicity, three types of cytotoxins have been established: vesicants, irritants and nonvesicant drugs.

Extravasation of Pt-based chemotherapeutics - bioimaging of their distribution in resectates using laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS).

Platinum-based drugs (cisplatin, carboplatin and oxaliplatin) are widely used in cancer treatment. They are administered intravenously, thus accidental extravasations of infusions can occur. This may cause severe complications for the patient as the toxic platinum compounds likely persist in subcutaneous tissue.

Outcome of chemotherapy extravasation in a large patient series using a standardised management protocol.

Purpose: In a longitudinal observation, extravasation of antitumoural compounds and the efficacy of its structured interdisciplinary management were assessed in a routine setting.

Methods: One hundred sixty-nine patients with extravasation of cytotoxics were managed according to a prospective approach documenting the extravasated compound, localisation, duration until full symptom resolution and sequelae. Surgery was implemented in the case of failure of conservative measures.

Indocyanine green video angiography predicts outcome of extravasation injuries.

Background: Extravasation of cytotoxic drugs is a serious complication of systemic cancer treatment. Still, a reliable method for early assessment of tissue damage and outcome prediction is missing. Here, we demonstrate that the evaluation of blood flow by indocyanine green (ICG) angiography in the extravasation area predicts for the need of surgical intervention.

The biomarker TP53 divides patients with neoadjuvantly treated esophageal cancer into 2 subgroups with markedly different outcomes. A p53 Research Group study.

Background: Fluorouracil and cisplatin have been used most frequently as neoadjuvant therapy for esophageal cancer. Both drugs are believed to act via a p53-dependent apoptosis pathway. The TP53 gene is frequently mutated in esophageal cancer.

Comparison between DCF (Docetaxel, Cisplatin and 5-Fluorouracil) and modified EOX (Epirubicin, Oxaliplatin and Capecitabine) as palliative first-line chemotherapy for adenocarcinoma of the upper gastrointestinal tract.

Background: The efficacy of triple-drug combination regimens such as docetaxel, cisplatin and 5-fluorouracil (DCF), and epirubicin, oxaliplatin and capecitabine (EOX), is superior to standard cisplatin/5-fluorouracil in patients with upper gastrointestinal adenocarcinoma. In this analysis, we compare DCF and EOX regarding toxicity and efficacy.

Patients And Methods: Patients received either intravenous docetaxel at 75 mg/m(2), cisplatin at 75 mg/m(2), both given on day 1, and 5-fluorouracil at 750 mg/m(2), on days 1 to 5, or epirubicin at 50 mg/m(2) i.

Combined contrast-enhanced magnetic resonance and diffusion-weighted imaging reading adapted to the "Breast Imaging Reporting and Data System" for multiparametric 3-T imaging of breast lesions.

Objective: To develop and assess a combined reading for contrast-enhanced magnetic resonance (CE-MRI) and diffusion weighted imaging (DWI) adapted to the BI-RADS for multiparametric MRI of the breast at 3 T.

Methods: A total of 247 patients with histopathologically verified breast lesions were included in this IRB-approved prospective study. All patients underwent CE-MR and DWI at 3 T.

Modified EOX (Epirubicin, Oxaliplatin and Capecitabine) as palliative first-line chemotherapy for gastroesophageal adenocarcinoma.

Background: The efficacy of triple-drug combination regimens such as epirubicin, oxaliplatin and capecitabine (EOX) is superior to standard cisplatin/5-fluorouracil, but considerable toxicity needs to be taken into account in patients with upper gastrointestinal adenocarcinoma. Therefore, we aimed to establish a modified version of the EOX regimen with improved tolerability for these patients.

Patients And Methods: Patients received palliative first-line chemotherapy with a modified EOX regimen repeated every three weeks (epirubicin 50 mg/m(2) i.

Plasma HMGB-1 after the initial dose of epirubicin/docetaxel in cancer.

Background: The response of breast cancer patients to neoadjuvant chemotherapy (NCT) is highly heterogeneous, and reliable predictive instruments remain to be defined. High-mobility group box-1 (HMGB-1) protein is a cell death marker, which is easily detectable in plasma. We hypothesized that the initial dose of NCT with epirubicin/docetaxel induces changes in plasma HMGB-1 which could allow for an early prediction of response to therapy.

Impact of HER-2-targeted therapy on overall survival in patients with HER-2 positive metastatic breast cancer.

Upon disease progression on trastuzumab-based therapy, patients with HER-2 positive metastatic breast cancer (MBC) may switch to lapatinib or continue on trastuzumab. We aimed to assess the impact of both strategies on overall survival (OS) in all patients treated for HER-2 positive MBC at the Medical University Vienna from 1999 until 2009. A total of 201 patients were identified from a breast cancer data base.

Ovarian function suppression and fulvestrant as endocrine therapy in premenopausal women with metastatic breast cancer.

Background: Endocrine therapy is the preferred treatment for hormone-receptor (HR) positive metastatic breast cancer. In premenopausal patients, ovarian function suppression with goserelin in combination with anastrozole yielded promising results in phase II studies. Fulvestrant, a pure antioestrogen, yields high rates of disease stabilisation in postmenopausal women.

Brain metastases free survival differs between breast cancer subtypes.

Background: Brain metastases (BM) are frequently diagnosed in patients with HER-2-positive metastatic breast cancer; in addition, an increasing incidence was reported for triple-negative tumours. We aimed to compare brain metastases free survival (BMFS) of breast cancer subtypes in patients treated between 1996 until 2010.

Methods: Brain metastases free survival was measured as the interval from diagnosis of extracranial breast cancer metastases until diagnosis of BM.

Impact of anti-HER2 therapy on overall survival in HER2-overexpressing breast cancer patients with brain metastases.

Background: Trastuzumab-based therapy after diagnosis of brain metastases (BM) may improve survival due to prolonged systemic disease control. We investigated whether lapatinib may yield additional survival benefit.

Methods: Eighty patients with BM from HER2-positive breast cancer were identified.

High resolution MRI of the breast at 3 T: which BI-RADS® descriptors are most strongly associated with the diagnosis of breast cancer?

Objective: To identify which breast lesion descriptors in the ACR BI-RADS® MRI lexicon are most strongly associated with the diagnosis of breast cancer when performing breast MR imaging at 3 T.

Methods: 150 patients underwent breast MR imaging at 3 T. Lesion size, morphology and enhancement kinetics were assessed according to the BI-RADS® classification.

Single-agent pegylated liposomal doxorubicin (PLD) in the treatment of metastatic breast cancer: results of an Austrian observational trial.

Background: In advanced breast cancer, multiple sequential lines of treatments are frequently applied. Pegylated liposomal doxorubicin (PLD) has a favourable toxicity profile and can be used in first or higher lines of therapy. PLD has demonstrated response activity even after prior anthracycline exposure.

Docetaxel, cisplatin and 5-fluorouracil plus granulocyte colony-stimulating factor prophylaxis in patients with metastatic adenocarcinoma of the stomach and gastroesophageal junction: experience at the Medical University of Vienna.

Background: A retrospective analysis was carried out to evaluate toxicity and efficacy of the combination chemotherapy of docetaxel, cisplatin and 5-fluorouracil (DCF) plus granulocyte colony-stimulating factor prophylaxis (G-CSF) in patients with metastatic gastric and gastroesophageal junction adenocarcinoma.

Patients And Methods: Eighteen patients received intravenous 75 mg/m2 docetaxel, 75 mg/m2 cisplatin, both given on day 1 and 750 mg/m2 5-fluorouracil, on days 1 to 5 plus G-CSF on day 6, all repeated every 3 weeks.

Results: Response rate was 28%, time to progression and overall survival were 26 and 54 weeks, respectively.

HER-2 status in primary oesophageal cancer, lymph nodes and distant metastases.

Background: Some 10-15 per cent of patients with oesophageal cancer overexpress human epidermal growth factor receptor (HER) 2 at the primary tumour site, leading to the hope that specific targeted systemic therapy might favourably influence clinical and subclinical disease at locoregional and distant sites. This approach is based on primary tumour characteristics, without knowledge of expression patterns at metastatic sites. In oesophageal cancer, concordance between HER-2 status at the primary tumour and other sites is unknown.

Expression of Her-2 in carcinomas of the esophagus.

The human epidermal growth factor receptor-2 gene (HER-2) encodes for a membrane-bound tyrosine kinase (Her-2), which is overexpressed in various human cancers. Her-2-targeted therapy has recently been shown to be beneficial for patients with advanced gastric cancer. Her-2 protein expression was investigated in 341 esophageal carcinomas [152 squamous cell carcinomas (SCC), 189 adenocarcinomas (AC)], 39 cases of Barrett mucosa, and 11 cases of squamous cell dysplasia.

Preoperative chemotherapy with cisplatin and docetaxel followed by surgery and clip-oriented postoperative chemoradiation in patients with localized gastric or gastroesophageal junction adenocarcinoma: results from a phase II feasibility study.

Background: We conducted a phase II feasibility study using preoperative chemotherapy with cisplatin and docetaxel followed by surgical resection and postoperative chemoradiation in patients with gastric or gastroesophageal cancer.

Methods: Preoperative chemotherapy (two or three cycles) consisted of 50 mg/m(2) docetaxel and 50 mg/m(2) cisplatin. Surgical resection was planned 4 weeks after the last chemotherapy cycle.

Capecitabine and Vinorelbine as an All-Oral Chemotherapy in HER2-Negative Locally Advanced and Metastatic Breast Cancer.

BACKGROUND: The oral formulation of vinorelbine together with capecitabine allows for an all-oral combination chemotherapy which promises to raise quality of life of patients with advanced breast cancer. PATIENTS AND METHODS: Patients with HER2-negative, locally advanced, inoperable or metastatic breast cancer were included in this prospective observational trial (treatment schedule: capecitabine 500 mg/m2 twice daily, days 1-14; vinorelbine 60 mg/m2, days 1+8; repeated in 3-week cycles). RESULTS: All 32 patients (median age 50 years) were evaluable for toxicity, and 30 patients for response.

Modulation of plasma complement by the initial dose of epirubicin/docetaxel therapy in breast cancer and its predictive value.

Background: Despite the widespread use of neoadjuvant chemotherapy in breast cancer patients, prediction of individual response to treatment remains an unsolved clinical problem. Particularly, administration of an inefficient chemotherapeutic regimen should be avoided. Therefore, a better understanding of the molecular mechanisms underlying response to neoadjuvant chemotherapy is of particular clinical interest.