Susanne Wiegand

Should We De-escalate the Treatment for HPV-Positive Tumors?

De-escalation or de-intensification of therapy is discussed since many retrospective analyses of former trials demonstrated significantly better outcome for patients suffering from p16/HPV16-positive oropharyngeal squamous cell carcinoma of head and neck (OHNSCC). These observations are comprehensively addressed, but the reader has to keep in mind that none of the currently discussed data result from prospective controlled trials addressing the HPV-discrimination in the primary endpoint design. Identification of the true HPV16-related tumors is still challenging and in addition with different clinical reports and lack of data of prospective trials not mature for routine clinical decision making in 2016. Independent of the currently lacking evidence for HPV-dependent treatment de-escalation, there are some relevant arguments to address this question in ongoing and future trials.

Information architecture for a patient-specific dashboard in head and neck tumor boards

PurposeOvercoming the flaws of current data management conditions in head and neck oncology could enable integrated information systems specifically tailored to the needs of medical experts in a tumor board meeting. Clinical dashboards are a promising method to assist various aspects of the decision-making process in such cognitively demanding scenarios. However, in order to provide extensive and intuitive assistance to the participating physicians, the design and development of such a system have to be user-centric. To accomplish this task, conceptual methods need to be performed prior to the technical development and integration stages.MethodsWe have conducted a qualitative survey including eight clinical experts with different levels of expertise in the field of head and neck oncology. According to the principles of information architecture, the survey focused on the identification and causal interconnection of necessary metrics for information assessment in the tumor board.ResultsBased on the feedback by the clinical experts, we have constructed a detailed map of the required information items for a tumor board dashboard in head and neck oncology. Furthermore, we have identified three distinct groups of metrics (patient, disease and therapy metrics) as well as specific recommendations for their structural and graphical implementation.ConclusionBy using the information architecture, we were able to gather valuable feedback about the requirements and cognitive processes of the tumor board members. Those insights have helped us to develop a dashboard application that closely adapts to the specified needs and characteristics, and thus is primarily user-centric.

Development of a Human Leukocyte Antigen Score to Predict Progression-Free Survival in Head and Neck Squamous Cell Carcinoma Patients

Background In personalized medicine and treatment stratification of head and neck squamous cell carcinoma (HNSCC), the heterogeneous genetic background of patients is not considered. Human leukocyte antigen (HLA) alleles and HLA haplotypes (HLA traits) are linked to development of HNSCC and affect progression-free survival (PFS) of HNSCC patients but most head and neck oncologists are not familiar with HLA typing. Hence, we developed an HLA-score abstracting from complexity of HLA-typing results to facilitate potential use of HLA-associated hazard ratios (HR) for prognostic stratification. Methods The HR for PFS of 8 HLA traits shown to be independent predictors (Pi) of PFS in a test cohort (TC) of 90 HNSCC patients were used to build the HLA-score based on the natural logarithm (ln) of the Pi-associated HR. Crude ln-transformed HR of the eight Pi, alleles B*13 (2), B*35 (1), B*51 (2), DQB1*06 (1), homozygous Cw (1), homozygous DRB4 (2), and haplotypes A*01/B*08 (−6) and B*08/C*07 (4), were summed up to yield the individual patient’s HLA-score. Receiver operating characteristic (ROC) and Kaplan–Meier curves were used to proof the suitability of the HLA-score as prognostic marker for PFS. An independent validation cohort (iVC) of 32 patients treated in the larynx-organ preservation trial DeLOS-II was utilized for validation. Results The individual HLA-scores (range −2 to 6) in TC classified HNSCC patients regarding PFS. ROC analysis (area under the curve = 0.750, 95% CI 0.665–0.836; P = 0.0000034) demonstrated an optimum cutoff for the HLA-score at 0.5 (97.9% sensitivity, 34.7% specificity), and 70/90 patients in TC with HLA-score > 0 had significant reduced PFS (P = 0.001). Applying the same classifier (HLA-score > 0) confirmed these findings in the iVC revealing reduced PFS of 25/32 patients (P = 0.040). Conclusion HLA traits constitute critical Pi. Considering the HLA-score may potentially facilitate the use of genetic information from HLA typing for prognostic stratification, e.g., within clinical trials.

Highlights from the Second International Symposium on HPV infection in head and neck cancer

The Second International Symposium on HPV Infection in Head and Neck Cancer was held on 3rd–4th November 2016 in Leipzig, Germany. The meeting brought together researchers and clinicians to share the latest knowledge on HPV infection in head and neck cancer and to join active and constructive scientific discussions. This report summarizes the major themes discussed during the symposium.

Conversion of hormone and HER-2 receptor in metachronous neck metastases from breast carcinoma

PurposeMetastases are a common event in breast cancer. The expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER-2) is essential for therapy and prognosis, and their conversion during disease progression potentially affects the treatment regimen. The aim was to analyze the estrogen, progesterone and HER-2 receptor expression in primary tumors and metachronous neck metastases from patients with breast cancer.MethodsA retrospective analysis of 27 patients with breast cancer and metachronous neck metastasis was performed. Distribution of neck metastasis to the neck levels and estrogen, progesterone and HER-2 receptor expression in primary tumor and metastasis were examined.ResultsThe most common localization of neck metastasis was level V. ER, PR, and HER-2 in primary tumors were positive in 48.1, 51.9, and 26.3% of patients, respectively. A loss of ER and PR in neck metastasis was observed in 22.2 and 40.7% of the patients, respectively. HER-2 change was present in 4 of 19 paired samples (21.0%).ConclusionsThe expression of ER, PR and HER-2 in neck metastases can be expected to diverge from the expression of these markers in the primary tumor. As such changes can occur during disease progression, the evaluation of biomarkers in metastatic sites should be mandatory, whenever possible, to ensure that patients are receiving the most effective treatment at all times.

Reduced Cytokine Release in Ex Vivo Response to Cilengitide and Cetuximab Is a Marker for Improved Survival of Head and Neck Cancer Patients

Targeting of αVβ3 and αVβ5 integrins by cilengitide may reduce growth of solid tumors including head and neck squamous cell carcinoma (HNSCC). Preclinical investigations suggest increased activity of cilengitide in combination with other treatment modalities. The only published trial in HNSCC (ADVANTAGE) investigated cisplatin, 5-fluorouracil, and cetuximab (PFE) without or with once (PFE+CIL1W) or twice weekly cilengitide (PFE+CIL2W) in recurrent/metastatic HNSCC. ADVANTAGE showed good tolerability of the cilengitide arms and even lower adverse events (AEs) compared to PFE but not the benefit in overall survival expected based on preclinical data. As we found in the FLAVINO assay, a short-time ex vivo assay for prediction of chemosensitivity, only a subgroup of HNSCC had an increased suppressive effect of cilengitide containing combination therapies on colony formation of epithelial cells (CFec) and release of pro-angiogenetic and pro-inflammatory cytokines, whereas other HNSCC failed to respond. Response to αVβ3 and αVβ5 integrin targeting by cilengitide classifies HNSCC regarding outcome. We present FLAVINO data arguing for further development of cilengitide plus cetuximab in treatment of a subgroup of HNSCC potentially identified by the FLAVINO assay using a set of biomarkers for response evaluation.