HPV status, cancer stem cell marker expression, hypoxia gene signatures and tumour volume identify good prognosis subgroups in patients with HNSCC after primary radiochemotherapy: A multicentre retrospective study of the German Cancer Consortium Radiation Oncology Group (DKTK-ROG)

Linge, Annett; Lohaus, Fabian; Löck, Steffen; Nowak, Alexander; Gudziol, Volker; Valentini, Chiara; Neubeck, Cläre von; Jütz, Martin; Tinhofer, Ingeborg; Budach, Volker; Sak, Ali; Stuschke, Martin; Balermpas, Panagiotis; Rödel, Claus; Grosu, Anca‐Ligia; Abdollahi, Amir; Debus, Jürgen; Ganswindt, Ute; Belka, Claus; Pigorsch, Steffi; Combs, Stephanie E.; Mönnich, David; Zips, Daniel; Buchholz, Frank; Aust, Daniela E.; Baretton, Gustavo; Thames, Howard D.; Dubrovska, Anna; Alsner, Jan; Overgaard, Jens; Krause, Mechthild; Baumann, Michaël

doi:10.1016/j.radonc.2016.11.008

Cited by 122 publications

(160 citation statements)

References 51 publications

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“…To the best of our knowledge, this is the first research studying a combined IHC CD44/EGFR profile in a group of patients treated with curative intent IMRT and, separately, in a p16 negative cohort. Furthermore, unlike most other studies on related topics, we have worked with a large cohort of patients …”

Section: Discussionmentioning

confidence: 99%

“…A variety of different biomarkers with promising diagnostic, prognostic, and predictive values are currently investigated in head and neck squamous cell carcinoma (HNSCC) . Finished and ongoing clinical trials have been evaluating the potential of reduced‐dose radiotherapy (RT) in less aggressive radiosensitive HNSCC defined by human papillomavirus (HPV) positivity, with the promise of less acute and late toxicity .…”

Section: Introductionmentioning

confidence: 99%

“…CD44‐expressing cells have an increased invasive and metastatic potential and increased proliferation index . CD44 expression correlated with worse outcomes in many different HNSCC entities . CD44 is a frequently studied cancer stem cell (CSC) marker in HNSCC, but the pan‐CD44 antibody recognizes all variants of CD44, thereby providing only limited knowledge about the relationship between specific CD44 variants and CSCs …”

Section: Introductionmentioning

confidence: 99%

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Expression of CD44, EGFR, p16, and their mutual combinations in patients with head and neck cancer: Impact on outcomes of intensity‐modulated radiation therapy

et al. 2018

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Background Progress in radiation treatment of head and neck squamous cell carcinoma (HNSCC) deserves the studies focused on molecular predictors that would help to enhance individually tailored treatment. Methods p16/epidermal growth factor receptor (EGFR)/cluster of differentiation‐44 (CD44) was immunohistochemically analyzed in 165 HNSCC patients. Results In the entire group and the p16 negative cohort, better 3‐year overall survival and locoregional control correlated with p16 positivity, CD44, and EGFR negativity were observed. Combined analysis revealed the worst results in the CD44+/p16−, EGFR+/p16−, and EGFR+/CD44+ groups and in the EGFR+/CD44+ within p16 negative cohort. Multivariate analysis found tumor stage, Karnofsky index, p16, and CD44 as prognostic factors of overall survival and clinical stage, and p16 as a prognostic factor for locoregional control. Clinical stage and Karnofsky index affected overall survival and tumor stage. EGFR affected locoregional control in the p16 negative subgroup. Conclusion Our study confirmed the negative effect of CD44 and EGFR and the positive effect of p16 on radiotherapy results.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Expression of CD44, EGFR, p16, and their mutual combinations in patients with head and neck cancer: Impact on outcomes of intensity‐modulated radiation therapy

et al. 2018

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“…In our study, which is part of the DKTK‐ROG initiative, which aims to identify and validate biomarkers for outcome of RCT in SCCHN, we aim to study the role of Hsp70 and tumor‐infiltrating NK cells as prognostic tumor biomarkers. Every year approximately 500,000 new cases are diagnosed worldwide with SCCHN with 4.8% of total cancer incidence and 4.6% cancer mortality .…”

Section: Introductionmentioning

confidence: 99%

Heat shock protein 70 and tumor‐infiltrating NK cells as prognostic indicators for patients with squamous cell carcinoma of the head and neck after radiochemotherapy: A multicentre retrospective study of the German Cancer Consortium Radiation Oncology Group (DKTK‐ROG)

Stangl

Tontcheva²,

Sievert

et al. 2017

Intl Journal of Cancer

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Tumor cells frequently overexpress heat shock protein 70 (Hsp70) and present it on their cell surface, where it can be recognized by pre‐activated NK cells. In our retrospective study the expression of Hsp70 was determined in relation to tumor‐infiltrating CD56+ NK cells in formalin‐fixed paraffin embedded (FFPE) tumor specimens of patients with SCCHN (N = 145) as potential indicators for survival and disease recurrence. All patients received radical surgery and postoperative cisplatin‐based radiochemotherapy (RCT). In general, Hsp70 expression was stronger, but with variable intensities, in tumor compared to normal tissues. Patients with high Hsp70 expressing tumors (scores 3–4) showed significantly decreased overall survival (OS; p = 0.008), local progression‐free survival (LPFS; p = 0.034) and distant metastases‐free survival (DMFS; p = 0.044), compared to those with low Hsp70 expression (scores 0–2), which remained significant after adjustment for relevant prognostic variables. The adverse prognostic value of a high Hsp70 expression for OS was also observed in patient cohorts with p16‐ (p = 0.001), p53‐ (p = 0.0003) and HPV16 DNA‐negative (p = 0.001) tumors. The absence or low numbers of tumor‐infiltrating CD56+ NK cells also correlated with significantly decreased OS (p = 0.0001), LPFS (p = 0.0009) and DMFS (p = 0.0001). A high Hsp70 expression and low numbers of tumor‐infiltrating NK cells have the highest negative predictive value (p = 0.00004). In summary, a strong Hsp70 expression and low numbers of tumor‐infiltrating NK cells correlate with unfavorable outcome following surgery and RCT in patients with SCCHN, and thus serve as negative prognostic markers.

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“…In line with this assumption, a recent study confirmed a significant association between tumor volume and locoregional control for patients with locally advanced HNSCC of the oral cavity, oropharynx, and hypopharynx [48]. Given the substantial evidence that a regenerative subpopulation of CSCs underlies the treatment-refractory nature of many HNSCC tumors, new therapies that target both CTCs and bulk tumor cells would have the potential to induce tumor regression and prevent local recurrence and distant relapse [49].…”

Section: The Concept Of Cancer Stem-like Cellsmentioning

confidence: 82%

Epidemiology and Molecular Biology of Head and Neck Cancer

2017

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Head and neck cancer is a common and aggressive malignancy with a high morbidity and mortality profile. Although the large majority of cases resemble head and neck squamous cell carcinoma (HNSCC), the current classification based on anatomic site and tumor stage fails to capture the high level of biologic heterogeneity, and appropriate clinical management remains a major challenge. Hence, a better understanding of the molecular biology of HNSCC is urgently needed to support biomarker development and personalized care for patients. This review focuses on recent findings based on integrative genomics analysis and multi-scale modeling approaches and how they are beginning to provide more sophisticated clues as to the biological and clinical diversity of HNSCC.

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HPV status, cancer stem cell marker expression, hypoxia gene signatures and tumour volume identify good prognosis subgroups in patients with HNSCC after primary radiochemotherapy: A multicentre retrospective study of the German Cancer Consortium Radiation Oncology Group (DKTK-ROG)

Cited by 122 publications

References 51 publications

Expression of CD44, EGFR, p16, and their mutual combinations in patients with head and neck cancer: Impact on outcomes of intensity‐modulated radiation therapy

Expression of CD44, EGFR, p16, and their mutual combinations in patients with head and neck cancer: Impact on outcomes of intensity‐modulated radiation therapy

Heat shock protein 70 and tumor‐infiltrating NK cells as prognostic indicators for patients with squamous cell carcinoma of the head and neck after radiochemotherapy: A multicentre retrospective study of the German Cancer Consortium Radiation Oncology Group (DKTK‐ROG)

Epidemiology and Molecular Biology of Head and Neck Cancer

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