Use of systematic analysis of DNA repair pathways in head and neck cancer (HNC) to identify XPF as a novel predictor of induction response, and pMK2 relationship to chemoradiotherapy.

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Meetings

Abstracts

2008 ASCO Annual Meeting

Use of systematic analysis of DNA repair pathways in head and neck cancer (HNC) to identify XPF as a novel predictor of induction response, and pMK2 relationship to chemoradiotherapy.

Sub-category:

Head and Neck Cancer

Category:

Head and Neck Cancer

Meeting:

2008 ASCO Annual Meeting

Session Type and Session Title:

Oral Presentation, Head and Neck Cancer

Abstract No:

6003

Citation:

J Clin Oncol 26: 2008 (May 20 suppl; abstr 6003)

Author(s):

T. Y. Seiwert, E. E. Cohen, X. Wang, M. Kocherginsky, M. Bhayani, K. Stenson, S. Finn, E. M. O'Regan, D. Weaver, E. E. Vokes

Abstract:

Background: Radiotherapy and most chemotherapeutic agents damage DNA and lack of adequate repair induces tumor cell death. Recently analysis of the nucleotide excision repair pathway identified ERCC1 as a predictor for platinating agents in multiple tumors. There are 6 DNA repair pathways which interrelate. We performed a more comprehensive analysis to identify clinically promising DNA repair biomarkers. Methods: 73 FFPE tumor samples from locally advanced HNC pts treated with carboplatin/taxane induction (I) followed by FHX-based chemoradiotherapy (CRT) were analyzed. IHC staining for 8 DNA repair biomarkers (5 pathways) was performed (ERCC1 (clone 8F1), XPF, pMK2, PARP, PAR1, pH2AX, MLH1, FANCD2), as well as relevant associated markers Ki67 (proliferation), EGFRvIII (truncated EGFR), p16 (HPV screen). IHC was analyzed by automated image processing, and 2 pathologists (blinded). Scores for nuclear/cytoplasmic intensity/quantity(IxQ) were correlated with response/survival. Immunoblot analysis in cell lines was done to determine antibody specificity. Further staining of 50pts (I+CRT) and 40pts (CRT) is ongoing. Results: Low levels of XPF were associated with response to induction chemotherapy (p=0.039). In contrast ERCC1 was marginally related to overall survival (p=0.085) and in our set did not correlate with response (p=0.41). pMK2 did not correlate with induction at all (p=0.74), but correlated with overall survival (p=0.026) suggesting that pMK2 may relate to CRT. EGFRvIII was positive in 48% of HNC. XPF, ERCC1, and MLH1 stained adjoining normal parabasal zones, whereas FANCD2 stained the suprabasal layer. An unsupervised cluster analysis suggests that ERCC1 and pMK2 associate. Immunoblot analysis of HNC tumor cell lines demonstrated multiple non-ERCC1 bands for the 8F1 antibody, suggesting limited specificity. Conclusion: XPF is a novel predictor of response to induction chemotherapy, which in our study worked better than ERCC1. pMK2 differentiated a subgroup with improved survival potentially related to CRT. Further study of pMK2 is needed and analysis of a CRT only cohort is ongoing. Analysis of multiple DNA repair markers holds promise.

Abstract Disclosures

Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy and are designated with a caret symbol (^) here and in the print version.

Associated Presentation(s):

1. Use of systematic analysis of DNA repair pathways in head and neck cancer (HNC) to identify XPF as a novel predictor of induction response, and pMK2 relationship to chemoradiotherapy.

Meeting: 2008 ASCO Annual Meeting
Presenter: Tanguy Y Seiwert, MD
Session: Head and Neck Cancer (Oral Presentation)

Other Abstracts in this Sub-Category:

		1. A phase II, randomized, non-comparative clinical trial of the effect of bevacizumab (BV) alone or in combination with irinotecan (CPT) on 6-month progression free survival (PFS6) in recurrent, treatment-refractory glioblastoma (GBM). Meeting: 2008 ASCO Annual Meeting Abstract No: 2010b First Author: T. F. Cloughesy Category: Head and Neck Cancer
		2. Concomitant chemoradiotherapy (CT/RT) vs neoadjuvant chemotherapy with docetaxel/cispaltin/5-fluorouracil (TPF) followed by CT/RT in locally advanced head and neck cancer. Final results of a phase II randomized study. Meeting: 2008 ASCO Annual Meeting Abstract No: 6000 First Author: A. Paccagnella Category: Head and Neck Cancer
		3. Cetuximab added to docetaxel, cisplatin, 5-fluorouracil Induction chemotherapy (C-TPF) in patients with newly diagnosed locally advanced head and neck cancer: A phase I study. Meeting: 2008 ASCO Annual Meeting Abstract No: 6001 First Author: R. B. Tishler Category: Head and Neck Cancer
		More...

Abstracts by T. Y. Seiwert :

		1. BIBW 2992 versus cetuximab in patients with metastatic or recurrent head and neck cancer (SCCHN) after failure of platinum-containing therapy with a cross-over period for progressing patients: Preliminary results of a randomized, open-label phase II study. Meeting: 2010 ASCO Annual Meeting Abstract No: 5501 First Author: T. Y. Seiwert Category: Head and Neck Cancer
		2. Phase II trial of sunitinib in medullary thyroid cancer (MTC). Meeting: 2010 ASCO Annual Meeting Abstract No: 5504 First Author: J. A. De Souza Category: Head and Neck Cancer
		3. Use of typical in-patient blood pressure measurements to detect bevacizumab-induced elevation in systolic pressure after the first infusion. Meeting: 2010 ASCO Annual Meeting Abstract No: e13622 First Author: M. R. Levine Category: Developmental Therapeutics - Experimental Therapeutics - Antiangiogenic Agents
		More...

Presentations by T. Y. Seiwert :

		1. BIBW 2992 versus cetuximab in patients with metastatic or recurrent head and neck cancer (SCCHN) after failure of platinum-containing therapy with a cross-over period for progressing patients: Preliminary results of a randomized, open-label phase II study. Meeting: 2010 ASCO Annual Meeting Presenter: Tanguy Y. Seiwert, MD Session: Promising Targeted Therapies for Head and Neck Cancer (Clinical Science Symposium)
		2. Use of DNA repair pathway analysis to predict overall survival in head and neck cancer patients treated with TFHX chemoradiotherapy. Meeting: 2009 ASCO Annual Meeting Presenter: Tanguy Y. Seiwert Session: Head and Neck Cancer (Poster Discussion)
		3. Use of systematic analysis of DNA repair pathways in head and neck cancer (HNC) to identify XPF as a novel predictor of induction response, and pMK2 relationship to chemoradiotherapy. Meeting: 2008 ASCO Annual Meeting Presenter: Tanguy Y Seiwert, MD Session: Head and Neck Cancer (Oral Presentation)
		More...

Educational Book Manuscripts by T. Y. Seiwert :

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