Publications by authors named "Thorsten Füreder"

11 Publications

  • Page 1 of 1

An analysis of distant metastasis cases from HPV-associated oropharyngeal squamous cell carcinoma.

J Craniomaxillofac Surg 2021 Apr 5;49(4):312-316. Epub 2021 Feb 5.

Department of Otorhinolaryngology, Medical University of Vienna, Vienna, Austria.

Although mostly associated with good survival outcomes, some patients with HPV-positive oropharyngeal squamous cell carcinoma develop distant metastasis and face dire prognosis. The aim of this study was to analyze distant metastatic patients in regards to survival, clinical staging, therapy approach and p16/HPV status. This retrospective single-centre study assessed patients with HPV-associated oropharyngeal cancer with distant metastasis treated in a tertiary referral center from 2005 to 2019. Overall- (OS) and survival after diagnosis of distant metastasis (OMS), clinical staging and different therapy approaches were assessed. Moreover, the overall mortality was assessed, as well as the association of different therapy approaches and p16/HPV status with the survival outcome. Out of 211 patients with HPV-associated oropharyngeal cancer that were treated in the study period, 15 developed distant metastases (7.1%). Median OS and OMS of the total group were 11 months (range 0.1-32 months) and 3 months (range 0.1-21 months), respectively. The overall mortality rate was 53.3% (n = 8). Significantly better outcome was present in patients treated with primary chemoradiotherapy (median OS 17 months vs. not reached, p = .03, median OMS 8 months vs not reached, p = .05). The OMS was significantly better in patients treated with chemotherapy initially after diagnosis (mean OMS 21 months vs 4 months; P = .001). Surgical resection after initial diagnosis was associated with a significantly shorter OMS (median OMS 3 vs. 21 months, p = .005). Interestingly, postoperative adjuvant therapy was delayed in all of these cases due to surgical site complications. Systemic treatment after initial diagnosis may be beneficial in clinical outcome of HPV associated distant metastases. Furthermore, surgical site complications should be treated with immediate care in order to avoid delay of adjuvant therapy. Further studies are warranted for validation of our results.
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http://dx.doi.org/10.1016/j.jcms.2021.01.012DOI Listing
April 2021

Molecularly guided treatment of metastatic parotid gland carcinoma in adults.

Wien Klin Wochenschr 2021 Jan 9;133(1-2):32-40. Epub 2020 Dec 9.

Department of Medicine I, Clinical Division of Oncology, Medical University of Vienna, Spitalgasse 23, 1090, Vienna, Austria.

Background: Advanced therapy-refractory parotid gland carcinomas have a poor prognosis with limited therapy options. We used molecular profiling to offer molecular guided therapies to patients with advanced metastatic parotid gland malignancies.

Methods: In this retrospective analysis we describe the molecular profiling of ten patients diagnosed with therapy-refractory metastatic parotid gland malignancies.

Results: We identified seven genetic aberrations in five patients: two mutations in CDKN2A and one mutation in APC, ATM, TP53, SMARCB1 and FGFR1, respectively. No mutations were detected in five patients. The IHC demonstrated frequent expressions of EGFR and p‑mTOR, as well as PTEN in eight patients. For four fifths (n = 8) of the patients, a targeted therapy was suggested. Eventually, three patients received the targeted therapy recommendation and one patient achieved stable disease for 14 months.

Conclusion: A total of eight therapy recommendations were provided. Based on our observations, molecular-guided therapies may be a feasible treatment approach for this rare disease entity.
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http://dx.doi.org/10.1007/s00508-020-01778-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840637PMC
January 2021

Creating the "new normal" post-Coronavirus world-web-communication replacing face-to-face interaction.

Memo 2020 21;13(3):245-246. Epub 2020 Sep 21.

Department of Oncology, Haematology and Palliative Care, Wilhelminen Hospital, Montleartstraße 37, 1160 Vienna, Austria.

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http://dx.doi.org/10.1007/s12254-020-00636-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7503050PMC
September 2020

Systemic Therapy, Palliation and Supportive Care of Patients with Hypopharyngeal Cancer.

Adv Otorhinolaryngol 2019 12;83:148-158. Epub 2019 Feb 12.

Department of Oto-Rhino-Laryngology, Klagenfurt General Hospital, Klagenfurt, Austria.

Hypopharyngeal cancer patients have a very poor prognosis and limited therapeutic options. Seventy to eighty per cent of all hypopharyngeal cancer patients will require palliative and/or end-of-life care for incurable end-stage disease during the course of their illness. The overall proportion of hypopharyngeal cancer patients not qualifying for initial curative treatment, or requiring palliation and supportive care over time is higher than for any other subsite of the head and neck. Surgery and radiotherapy usually have a very limited role in this setting, while systemic therapy will usually compete with supportive care as the best approach. Advances in medicine and oncological treatments for the management of patients with recurrent head and neck cancer have given physicians the opportunity to prolong life where possible. However, this increase in survival might not be clinically meaningful if patients do not simultaneously experience palliative benefits, such as a reduction in symptoms and an improvement in their overall quality of life (QoL). The optimal outcome of palliative treatment is the control of symptoms with minimal treatment toxicities while improving QoL. It remains unclear if current palliative treatment options are better at improving QoL than the best supportive care. An intervention that results in insufficient or unacceptable functional status to the extent that the patient cannot achieve treatment goals - even in the course of prolonging life - is questionable. When used for palliative care purposes, surgery, chemotherapy and radiotherapy commonly have limited effectiveness in improving QoL. Moreover, if these treatments are not congruent with a patient's end-of-life goals, they could constitute low-value care.
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http://dx.doi.org/10.1159/000492359DOI Listing
August 2019

PD-1 and PD-L1 expression in HNSCC primary cancer and related lymph node metastasis - impact on clinical outcome.

Histopathology 2018 Oct 4;73(4):573-584. Epub 2018 Jul 4.

Department of Otorhinolaryngology, Head and Neck Surgery, Vienna, Austria.

Aims: Expression profiles and clinical impact of programmed cell death ligand 1 (PD-L1) and programmed cell death 1 (PD-1) expressing tumour infiltrating lymphocytes (TILs) in head and neck squamous cell carcinoma (HNSCC) are not elucidated fully. This study evaluates expression patterns in primary HNSCC and related lymph node metastasis and the impact on patients' clinical outcome.

Methods And Results: Immunohistochemical staining patterns of PD-L1 and PD-1 were evaluated in 129 specimens of primary HNSCC and 77 lymph node metastases. Results were correlated with patients' clinical data. PD-L1 expression was observed in 36% of primary carcinoma and 33% of lymph node metastasis, and correlates significantly with decreased overall survival (OS) (P = 0.01) and disease-free survival (DFS) (P = 0.001) in oral cavity squamous cell carcinoma patients. PD-L1 expression was associated with presence of lymph node metastasis (P = 0.0223). Infiltration of PD-1-expressing lymphocytes correlates significantly with favourable OS (P = 0.001) and DFS (P = 0.001) in oropharyngeal cancer and hypopharyngeal cancer patients OS (P = 0.007) and DFS (P = 0.001). Presence of PD-1 TILs also correlates significantly with better OS (P = 0.005) and DFS (P = 0) in the human papilloma virus (HPV)-negative cohort. Cox regression multivariate analysis revealed PD-1 TIL expression as an independent prognostic marker for OS (P = 0.004) and DFS (P = 0.001) and T stage was validated as negative prognostic marker for OS (P = 0.011). PD-1-expressing lymphocytes (P = 0.0412) and PD-L1 expression (P = 0.0022) patterns correlate significantly in primary cancers and matched lymph node metastases.

Conclusions: Our results characterise the expression profiles of PD-1 axis proteins in HNSCC which might serve as possible clinical prognostic markers.
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http://dx.doi.org/10.1111/his.13646DOI Listing
October 2018

Review of cancer treatment with immune checkpoint inhibitors : Current concepts, expectations, limitations and pitfalls.

Wien Klin Wochenschr 2018 Feb 2;130(3-4):85-91. Epub 2017 Nov 2.

Clinical Division of Oncology, Department of Medicine I, General Hospital, Währinger Gürtel 18-20, 1090, Vienna, Austria.

Immunotherapy by checkpoint inhibition is about to profoundly change cancer therapy. The number of indications are growing at an unprecedented speed. Clinical studies have demonstrated efficacy in a variety of solid tumors and in hematologic malignancies, although some clinical trials have produced negative results. Thus, it is fair to assume that there are obvious limitations and pitfalls in immunotherapy. Future concepts for combination treatment of immune checkpoint inhibitors have to be developed, but there is also urgent need for better and standardized biomarkers to identify those cancer patients who will benefit from treatment by checkpoint inhibition. The current overview summarizes current knowledge on immune checkpoint inhibitor treatment in malignancies, its outlook and limitations, diagnostic means and, finally, side effect management.
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http://dx.doi.org/10.1007/s00508-017-1285-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5816095PMC
February 2018

A Cross-Sectional Study of Patients' Satisfaction With Totally Implanted Access Ports.

Clin J Oncol Nurs 2016 Apr;20(2):175-80

Medical University of Vienna.

Background: Totally implanted access ports (PACs) are valuable tools for the treatment of patients with cancer because they ease the administration of chemotherapy, stem cells, and supportive care by reducing the rate of peripheral vein punctures.

Objectives: The purpose of this study was to evaluate the satisfaction and impairments of activities of daily living of ambulatory patients with PAC systems receiving chemotherapy.

Methods: This cross-sectional, questionnaire-based study evaluated 202 patients with PAC systems in a comprehensive cancer center and cancer rehabilitation center. From November 2012 to August 2013, patients were invited to answer a questionnaire concerning quality of life and satisfaction with their PAC devices. Data regarding PAC-related complications were collected retrospectively by searching patients' medical history.

Findings: A total of 202 patients with 230 PAC devices were included. Median time from PAC implantation to inclusion in the study was nine months. Surgical complications occurred in some cases, with bleeding and hematoma being the most frequently observed events. Late complications consisted of infections, drug extravasation, PAC malposition, PAC malfunction, and thrombosis. A third of the patients reported that their PAC interfered with activities of daily living. However, most agreed that PAC systems alleviated the burden of chemotherapy administration, and the vast majority said they would choose the implantation of a PAC system for chemotherapy administration again.
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http://dx.doi.org/10.1188/16.CJON.175-180DOI Listing
April 2016

Safety and feasibility of every-other-week maintenance cetuximab after first-line chemotherapy in patients with recurrent or metastatic head and neck squamous cell cancer.

Head Neck 2013 Oct 6;35(10):1471-4. Epub 2012 Oct 6.

Head and Neck Medical Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.

Background: In patients with recurrent and/or metastatic head and neck squamous cell cancer (HNSCC), there are no data about an every-other-week cetuximab maintenance schedule after chemotherapy plus cetuximab as first-line treatment.

Methods: We reviewed the safety and feasibility of every-other-week maintenance cetuximab administered at 3 different European centers.

Results: Thirty-one patients with recurrent or metastatic HNSCC were treated from 2006 to 2010. Mean cetuximab dose intensity in the maintenance phase was 93%. The major toxicities reported during every-other-week maintenance cetuximab were skin rash (grade 3, 16%; grade 2, 23%), fatigue (grade 3, 3%; grade 2, 16%), diarrhea (grade 3, 7%; grade 2, 13%), hypomagnesemia (grade 4, 3%; grade 3, 3%; grade 2, 19%), and mucositis (grade 3, 3%; grade 2, 23%).

Conclusions: Every-other-week maintenance cetuximab schedule was well tolerated and did not worsen toxicity that occurred during chemotherapy. In daily practice, this simplified schedule could improve compliance and possibly improve quality of life in patients with recurrent or metastatic HNSCC that showed no progression during first-line chemotherapy.
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http://dx.doi.org/10.1002/hed.23170DOI Listing
October 2013

[Therapy of castration-resistant prostate cancer].

Wien Klin Wochenschr 2012 Aug 20;124(15-16):538-51. Epub 2012 Jul 20.

Urologische Abteilung, Donauspital, Wien, Österreich.

Within the last two years the therapy of castration resistant prostate cancer (CRPC) has made major advances. Both the COU-AA-301 phase III trial and the TROPIC trial showed a survival benefit for patients after docetaxel failure treated with abiraterone or cabazitaxel, respectively. With rising interest for chemotherapeutic options and novel drugs, our goal was to review within the context of a multidisciplinary team the available evidence and explore the standards for medical treatment of prostate cancer outside of clinical trials. From this background, we are carefully evaluating the current treatment recommendations, based on the available evidence, and highlight potential future treatment options but also discuss important clinical topics like treatment until progression versus the advantage of chemo holidays and definition of particular patient subgroups. Additionally, we focus on novel molecular entities, which will most likely be available in the near future, such as MDV3100 and Sipuleucel T. The role and importance of palliation with radiotherapy and proactive medical management of pain is also discussed, as well as new options for bone directed therapy. The multitude of treatment options for patients with advanced prostate cancer clearly asks for a close collaboration between urologists, medical oncologists and radiation therapists.
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http://dx.doi.org/10.1007/s00508-012-0206-1DOI Listing
August 2012

The PI3-kinase/mTOR-targeting drug NVP-BEZ235 inhibits growth and IgE-dependent activation of human mast cells and basophils.

PLoS One 2012 27;7(1):e29925. Epub 2012 Jan 27.

Division of Hematology and Hemostaseology, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria.

The phosphoinositide 3-kinase (PI3-kinase) and the mammalian target of rapamycin (mTOR) are two major signaling molecules involved in growth and activation of mast cells (MC) and basophils (BA). We examined the effects of the dual PI3-kinase/mTOR blocker NVP-BEZ235 on growth of normal and neoplastic BA and MC as well as immunoglobulin E (IgE)-dependent cell activation. Growth of MC and BA were determined by measuring (3)H-thymidine uptake and apoptosis. Cell activation was determined in histamine release experiments and by measuring upregulation of CD63 and CD203c after challenging with IgE plus anti-IgE or allergen. We found that NVP-BEZ235 exerts profound inhibitory effects on growth of primary and cloned neoplastic MC. In the MC leukemia cell line HMC-1, NVP-BEZ235 showed similar IC(50) values in the HMC-1.1 subclone lacking KIT D816V (0.025 µM) and the HMC-1.2 subclone expressing KIT D816V (0.005 µM). Moreover, NVP-BEZ235 was found to exert strong growth-inhibitory effects on neoplastic MC in a xenotransplant-mouse model employing NMR1-Foxn1(nu) mice. NVP-BEZ235 also exerted inhibitory effects on cytokine-dependent differentiation of normal BA and MC, but did not induce growth inhibition or apoptosis in mature MC or normal bone marrow cells. Finally, NVP-BEZ235 was found to inhibit IgE-dependent histamine release in BA and MC (IC(50) 0.5-1 µM) as well as anti-IgE-induced upregulation of CD203c in BA and IgE-dependent upregulation of CD63 in MC. In summary, NVP-BEZ235 produces growth-inhibitory effects in immature neoplastic MC and inhibits IgE-dependent activation of mature BA and MC. Whether these potentially beneficial drug effects have clinical implications is currently under investigation.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0029925PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3267720PMC
July 2012

Dose study of the multikinase inhibitor, LY2457546, in patients with relapsed acute myeloid leukemia to assess safety, pharmacokinetics, and pharmacodynamics.

Cancer Manag Res 2011 10;3:157-75. Epub 2011 May 10.

Department of Clinical Pharmacology, Medical University of Vienna, Währinger Gürtel, Vienna, Austria;

Background: Acute myeloid leukemia (AML) is a life-threatening malignancy with limited treatment options in chemotherapy-refractory patients. A first-in-human dose study was designed to investigate a safe and biologically effective dose range for LY2457546, a novel multikinase inhibitor, in patients with relapsed AML.

Methods: In this nonrandomized, open-label, dose escalation Phase I study, LY2457546 was administered orally once a day. Safety, pharmacokinetics, changes in phosphorylation of target kinases in AML blasts, and risk of drug-drug interactions (DDI) were assessed.

Results: Five patients were treated at the starting and predicted minimal biologically effective dose of 50 mg/day. The most commonly observed adverse events were febrile neutropenia, epistaxis, petechiae, and headache. The majority of adverse events (81%) were Grade 1 or 2. One patient had generalized muscle weakness (Grade 3), which was deemed to be a dose-limiting toxicity. Notably, the pharmacokinetic profile of LY2457546 showed virtually no elimination of LY2457546 within 24 hours, and thus prevented further dose escalation. No significant DDI were observed. Ex vivo flow cytometry studies showed downregulation of the phosphoproteins, pcKIT, pFLT3, and pS6, in AML blasts after LY2457546 administration. No medically relevant responses were observed in the five treated patients.

Conclusion: No biologically effective dose could be established for LY2457546 in chemotherapy-resistant AML patients. Lack of drug clearance prevented safe dose escalation, and the study was terminated early. Future efforts should be made to develop derivatives with a more favorable pharmacokinetic profile.
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http://dx.doi.org/10.2147/CMR.S19341DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3101112PMC
July 2011