HPV16 DNA status is a strong prognosticator of loco-regional control after postoperative radiochemotherapy of locally advanced oropharyngeal carcinoma: Results from a multicentre explorative study of the German Cancer Consortium Radiation Oncology Group (DKTK-ROG)

Lohaus, Fabian; Linge, Annett; Tinhofer, Ingeborg; Budach, Volker; Gkika, Eleni; Stuschke, Martin; Balermpas, Panagiotis; Rödel, Claus; Avlar, Melanie; Grosu, Anca‐Ligia; Abdollahi, Amir; Debus, Jürgen; Bayer, Christine; Belka, Claus; Pigorsch, Steffi; Combs, Stephanie E.; Mönnich, David; Zips, Daniel; Neubeck, Cläre von; Baretton, Gustavo; Löck, Steffen; Thames, Howard D.; Krause, Mechthild; Baumann, Michaël

doi:10.1016/j.radonc.2014.11.011

Cited by 127 publications

(150 citation statements)

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“…HPV-positive tumors are more radio(chemo) sensitive than HPV-negative tumors (7,8) and locoregional control after PORT-C was achieved in our analysis in virtually all patients with HPV16 DNA-positive tumors (6). In contrast, in patients with HPV16 DNA-negative tumors locoregional control rates of approximately 80% were reached, implying that the HPV16 DNA infection status is not suitable as a sole biomarker for the prediction of locoregional tumor recurrences in these patients.…”

Section: Introductionmentioning

confidence: 61%

“…Previously, we and others have shown that the HPV infection status is a strong prognosticator for locoregional control in patients with locally advanced HNSCC who received postoperative radio(chemo)therapy (6,28,29) with an improved locoregional control and radiosensitivity of HPV16 DNA positive in comparison with HPV16 DNA-negative tumors. In our previous multicenter evaluation, we found virtually no recurrences in the HPV16 DNA-positive group among high-risk HNSCC patients who received PORT-C (6).…”

Section: Discussionmentioning

confidence: 91%

“…The patient eligibility criteria have been described previously (6). Briefly, patients with histologically proven squamous cell carcinoma arising from the oral cavity, oropharynx, or hypopharynx who were treated between 2004 and 2012 in eight DKTK partner sites were included in this study.…”

Section: Patientsmentioning

confidence: 99%

“…The multivariate analyses also included extracapsular extension (ECE) status (significant for secondary endpoints) and tumor localization, because these variables were significant prognostic factors in our previous analysis (6). Both hypoxia gene classifiers revealed a significant association of tumors classified as "hypoxic" with poor locoregional control (15-gene classifier: HR 3.73, P ¼ 0.008; 26-gene classifier: HR 6.00, P ¼ 0.017; Supplementary Table S3).…”

Section: Hypoxia Gene Expressionmentioning

confidence: 99%

“…Recently, we have shown in a systematic multicentric retrospective evaluation that the human papillomavirus type 16 deoxyribonucleic acid (HPV16 DNA) status is a strong prognosticator for locoregional control after PORT-C in HNSCC, especially in patients with locally advanced oropharyngeal squamous cell carcinomas (6). HPV-positive tumors are more radio(chemo) sensitive than HPV-negative tumors (7,8) and locoregional control after PORT-C was achieved in our analysis in virtually all patients with HPV16 DNA-positive tumors (6).…”

Section: Introductionmentioning

confidence: 99%

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Low Cancer Stem Cell Marker Expression and Low Hypoxia Identify Good Prognosis Subgroups in HPV(−) HNSCC after Postoperative Radiochemotherapy: A Multicenter Study of the DKTK-ROG

Linge

Löck

Gudziol

et al. 2016

Clinical Cancer Research

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Purpose: To investigate the impact of hypoxia-induced gene expression and cancer stem cell (CSC) marker expression on outcome of postoperative cisplatin-based radiochemotherapy (PORT-C) in patients with locally advanced head and neck squamous cell carcinoma (HNSCC).Experimental Design: Expression of the CSC markers CD44, MET, and SLC3A2, and hypoxia gene signatures were analyzed in the resected primary tumors using RT-PCR and nanoString technology in a multicenter retrospective cohort of 195 patients. CD44 protein expression was further analyzed in tissue microarrays. Primary endpoint was locoregional tumor control.Results: Univariate analysis showed that hypoxia-induced gene expression was significantly associated with a high risk of locoregional recurrence using the 15-gene signature (P ¼ 0.010) or the 26-gene signature (P ¼ 0.002). In multivariate analyses, in patients with HPV16 DNA-negative but not with HPV16 DNA-positive tumors the effect of hypoxia-induced genes on locoregional control was apparent (15-gene signature: HR 4.54, P ¼ 0.006; 26-gene signature: HR 10.27, P ¼ 0.024). Furthermore, MET, SLC3A2, CD44, and CD44 protein showed an association with locoregional tumor control in multivariate analyses (MET: HR 3.71, P ¼ 0.016; SLC3A2: HR 8.54, P ¼ 0.037; CD44: HR 3.36, P ¼ 0.054; CD44 protein n/a because of no event in the CD44-negative group) in the HPV16 DNA-negative subgroup.Conclusions: We have shown for the first time that high hypoxia-induced gene expression and high CSC marker expression levels correlate with tumor recurrence after PORT-C in patients with HPV16 DNA-negative HNSCC. After validation in a currently ongoing prospective trial, these parameters may help to further stratify patients for individualized treatment de-escalation or intensification strategies.

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Section: Introductionmentioning

confidence: 61%

Section: Discussionmentioning

confidence: 91%

Section: Patientsmentioning

confidence: 99%

Section: Hypoxia Gene Expressionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Low Cancer Stem Cell Marker Expression and Low Hypoxia Identify Good Prognosis Subgroups in HPV(−) HNSCC after Postoperative Radiochemotherapy: A Multicenter Study of the DKTK-ROG

Linge

Löck

Gudziol

et al. 2016

Clinical Cancer Research

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Specific requirements for translation of biological research into clinical radiation oncology

et al. 2020

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Radiotherapy has been optimized over the last decades not only through technological advances, but also through the translation of biological knowledge into clinical treatment schedules. Optimization of fractionation schedules and/or the introduction of simultaneous combined systemic treatment have significantly improved tumour cure rates in several cancer types. With modern techniques, we are currently able to measure factors of radiation resistance or radiation sensitivity in patient tumours; the definition of new biomarkers is expected to further enable personalized treatments. In this Review article, we overview important translation paths and summarize the quality requirements for preclinical and translational studies that will help to avoid bias in trial results. Abbreviations CD44, cluster of differentiation 44 (cell surface molecule); CXCR-4, C-X-C motif chemokine receptor 4; DAHANCA, Danish Head and Neck Cancer Group; DKTK, German Cancer Consortium; EGFR, epidermal growth factor receptor; FAZA, [18F]-fluoroazomycin arabinoside (hypoxia PET tracer); FMISO, [18F]-fluoromisonidazole (hypoxia PET tracer); HNSCC, head and neck squamous cell carcinoma; HPV, human papillomavirus; PET, positron emission tomography.

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What will radiation oncology look like in 2050? A look at a changing professional landscape in Europe and beyond

et al. 2020

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The number of newly diagnosed cancers per year is predicted to almost double in the next two decades worldwide, and it remains unclear if and when this alarming trend will level off or even reverse. As such, cancer is very likely to continue to pose a major threat to human health. Radiation oncology is an indispensable pillar of cancer treatment and a well‐developed discipline. Nevertheless, key trends in cancer research and care, including improved primary prevention, early detection, integrated multidisciplinary approaches, personalized strategies at all levels of care, value‐based assessments of healthcare systems, and global health perspectives, will all shape the future of radiation oncology. Broader scientific advances, such as rapid progress in digitization, automation, and in our biological understanding of cancer, as well as the wider societal view of healthcare systems will also influence radiation oncology and how it is practiced. To stimulate a proactive discussion on how to adapt and reshape our discipline, this review provides some predictions on what the role and practice of radiation oncology might look like in 30 years’ time.

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HPV16 DNA status is a strong prognosticator of loco-regional control after postoperative radiochemotherapy of locally advanced oropharyngeal carcinoma: Results from a multicentre explorative study of the German Cancer Consortium Radiation Oncology Group (DKTK-ROG)

Abstract: HPV16 DNA status appears to be a strong prognosticator of loco-regional tumour control after postoperative cisplatin-based radiochemotherapy of locally advanced oropharyngeal carcinoma and is now being explored in a prospective validation trial.

Cited by 127 publications

References 41 publications

Low Cancer Stem Cell Marker Expression and Low Hypoxia Identify Good Prognosis Subgroups in HPV(−) HNSCC after Postoperative Radiochemotherapy: A Multicenter Study of the DKTK-ROG

Low Cancer Stem Cell Marker Expression and Low Hypoxia Identify Good Prognosis Subgroups in HPV(−) HNSCC after Postoperative Radiochemotherapy: A Multicenter Study of the DKTK-ROG

Specific requirements for translation of biological research into clinical radiation oncology

What will radiation oncology look like in 2050? A look at a changing professional landscape in Europe and beyond

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