High-grade acute organ toxicity and p16INK4A expression as positive prognostic factors in primary radio(chemo)therapy for patients with head and neck squamous cell carcinoma

Tehrany, Narges; Kitz, Julia; Rave-Fränk, Margret; Lorenzen, Stephan; Li, Li; Küffer, Stefan; Hess, Clemens F.; Burfeind, Peter; Reichardt, Holger M.; Canis, Martin; Beißbarth, Tim; Wolff, Hendrik A.

doi:10.1007/s00066-014-0801-3

Cited by 21 publications

(21 citation statements)

References 29 publications

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“…The prognostic impact of HPV positivity has been demonstrated by several investigations [2,5,6]. Up to now there has been little information about the influence of HPV infection on toxicity rates during combined treatment.…”

Section: Discussionmentioning

confidence: 99%

“…A study analyzing 233 HNSCC patients showed that p16 expression and high toxicity rates were independent prognostic factors. An interrelationship between p16 expression and radiation-induced reactions was discussed [6]. …”

Section: Discussionmentioning

confidence: 99%

“…Concurrent radiochemotherapy (RCT) is the standard treatment for patients suffering from locally advanced HNSCC. Although promising rates of tumor control can be achieved with this regimen, aggressive RCT is associated with high rates of side effects [5,6,7]. The finding that patients with p16-positive tumors might experience toxicities that are more pronounced than in p16-negative patients indicates a need for adjusting supportive care procedures.…”

Section: Introductionmentioning

confidence: 99%

“…Studies have shown that there is a significant correlation between hemoglobin level and tumor oxygenation in HNSCC patients [4]. In addition, the clinical impact of genetic alterations such as HPV/p16 expression on toxicities has been discussed [5,6]. Concurrent radiochemotherapy (RCT) is the standard treatment for patients suffering from locally advanced HNSCC.…”

Section: Introductionmentioning

confidence: 99%

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Impact of p16 Alterations and Pretreatment Anemia on Toxicity in Head and Neck Cancer Patients Undergoing Definitive Radiochemotherapy

et al. 2015

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Background: Human papilloma virus (HPV) infection, p16 expression and hypoxia may play important roles in the carcinogenesis, treatment response and toxicities of head and neck squamous cell carcinoma (HNSCC). The aim of this analysis was to assess whether there is any correlation between pre-radiotherapy (RT) anemia, p16 expression and toxicities and local control for patients undergoing definitive therapy. Methods: 79 HNSCC patients who had undergone radiochemotherapy (RCT) or RT-antibody therapy were retrospectively analyzed. p16 (INK4A) expression was detected by immunohistochemical analysis. Factors predisposing for acute side effects were examined by uni- and multivariate analysis. Results: p16 overexpression was detected in 32 cases. Pretreatment anemia was present in one third of patients. Only 5% of patients were characterized by both pre-RT anemia and p16 overexpression. p16 expression was significantly associated with acute grade 3 toxicity. 47% of p16-positive patients developed grade ≥ 3 radiodermatitis compared to 26% of p16-negative patients (p = 0.04). A reduced risk of severe skin toxicities was noted for patients with hypoxic blood values before RT. p16 expression was significantly correlated with local control (p = 0.002). Conclusions: p16 expression is associated with better response to definitive combined treatment (RCT, RT + cetuximab), but also significantly related to acute high-grade toxicity.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Impact of p16 Alterations and Pretreatment Anemia on Toxicity in Head and Neck Cancer Patients Undergoing Definitive Radiochemotherapy

et al. 2015

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“…Immunohistochemistry of paraffin sections was carried out using an immunohistochemical double staining method including streptavidin biotinylated alkaline phosphatase (ABC-AP, DakoCytomation, Hamburg, Germany). 17,18 Each paraffin section was double stained with the following primary antibodies FoxP3-CD1, (Abcam, Cambridge, United Kingdom-DakoCytomation, Hamburg, Germany), FoxP3-CD8 + (Abcam-DakoCytomation, Fig. 1B), FoxP3-CD20 (Abcam-DakoCytomation) followed by secondary antibody.…”

Section: Treatment Protocolmentioning

confidence: 99%

Cell-to-cell distances between tumor-infiltrating inflammatory cells have the potential to distinguish functionally active from suppressed inflammatory cells

et al. 2016

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Beyond their mere presence, the distribution pattern of inflammatory cells is of special interest. Our hypothesis was that random distribution may be a clear indicator of being non-functional as a consequence of lack of interaction. Here, we have assessed the implication of cell-to-cell distances among inflammatory cells in anal squamous cell carcinoma and a possible association with survival data. Thirtyeight patients suffering from anal carcinoma were studied using tissue microarrays, double staining immunohistochemistry, whole slide scanning and image analysis software. Therapy consisted of concurrent radiochemotherapy. Numbers of stromal and intraepithelial tumor-infiltrating inflammatory cells (TIC) and the distances between cells were quantified. Double-staining of FoxP3 + cells with either CD8 + , CD1a + or CD20 + cells was performed. Measured cell-to-cell distances were compared to computer simulated cell-to-cell distances leading to the assumption of non-randomly distributed and therefore functional immune cells. Intraepithelial CD1a + and CD20 + cells were randomly distributed and therefore regarded as non-functional. In contrary, stromal CD20 + cells had a non-random distribution pattern. A non-random distance between CD20 + and FoxP3 + cells was associated with a clearly unfavorable outcome. Measured distances between FoxP3 + cells were distinctly shorter than expected and indicate a functional active state of the regulatory T cells (Treg). Analysis of cell-to-cell distances between TIC has the potential to distinguish between suppressed non-functional and functionally active inflammatory cells. We conclude that in this tumor model most of the CD1a + cells are non-functional as are the intraepithelial CD20 + cells, while stromal CD20 + cells and FoxP3 + cells are functional cells.

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Investigation of p16 status, chemotherapy regimen, and other nutrition markers for predicting gastrostomy in patients with head and neck cancer

et al. 2017

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High-grade acute organ toxicity and p16INK4A expression as positive prognostic factors in primary radio(chemo)therapy for patients with head and neck squamous cell carcinoma

Abstract: P16(INK4A) expression and HGAOT are independent prognostic factors for OS of patients with HNSCC, whereas p16(INK4A) expression is particularly important for patients without HGAOT.

Cited by 21 publications

References 29 publications

Impact of p16 Alterations and Pretreatment Anemia on Toxicity in Head and Neck Cancer Patients Undergoing Definitive Radiochemotherapy

Impact of p16 Alterations and Pretreatment Anemia on Toxicity in Head and Neck Cancer Patients Undergoing Definitive Radiochemotherapy

Cell-to-cell distances between tumor-infiltrating inflammatory cells have the potential to distinguish functionally active from suppressed inflammatory cells

Investigation of p16 status, chemotherapy regimen, and other nutrition markers for predicting gastrostomy in patients with head and neck cancer

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