Effective Biomarkers and Radiation Treatment in Head and Neck Cancer

Ow, Thomas J.; Pitts, Casey; Kabarriti, Rafi; Garg, Madhur

doi:10.5858/arpa.2014-0574-ra

Cited by 13 publications

(17 citation statements)

References 128 publications

(134 reference statements)

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“…This might be explained by population diversity in TNM stages, immunohistochemical techniques, staining evaluation methodologies, and anatomical tumor sublocalizations. [24][25][26] Previously, we studied the association between local control and expression of several markers in separate homogeneous cohorts of T1-T2 glottic and supraglottic LSCC, all treated with radiotherapy only. This association with some markers observed in the glottic cohort, 7,8 could not be confirmed in the supraglottic cohort.…”

Section: Discussionmentioning

confidence: 99%

Distinct Biomarker Profiles and Clinical Characteristics in T1‐T2 Glottic and Supraglottic Carcinomas

et al. 2020

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Background: In early stage laryngeal squamous cell carcinoma (LSCC) radiotherapy with curative intent is a major treatment modality. TNM classification is used to define patients eligible for radiotherapy. Studies in early stage glottic LSCC identified several predictive biomarkers associated with local control. However, we recently reported that this predictive value could not be confirmed in supraglottic LSCC. Objective: To examine whether clinical behavior and protein expression patterns of these biomarkers differ between glottic and supraglottic LSCC. Study Design: Retrospective cohort study. Methods: Tumor tissue sections of 196 glottic and 80 supraglottic T1-T2 LSCC treated primarily with RT were assessed immunohistochemically for expression of pAKT, Ki-67 and β-Catenin. Expression data of HIF-1α, CA-IX, OPN, FADD, pFADD, Cyclin D1, Cortactin and EGFR in the same cohort of glottic and supraglottic LSCC, were retrieved from previously reported data. The relationship between glottic and supraglottic sublocalization and clinicopathological, follow-up, and immunohistochemical staining characteristics were evaluated using logistic regression and Cox regression analyses. Results: Glottic LSCC were correlated with male gender (P = .001), hoarseness as a primary symptom (P < .001), T1 tumor stage (P < .001), negative lymph node status (P < .001), and an older age at presentation (P = .004). Supraglottic LSCC patients developed more post-treatment distant metastasis when adjusted for gender, age, and T-status. While supraglottic LSCC was associated with higher expression of HIF-1α (P = .001), Cortactin (P < .001), EGFR (P < .001), and Ki-67 (P = .027), glottic LSCC demonstrated higher expression of CA-IX (P = .005) and Cyclin D1 (P = .001). Conclusion: Differences in clinicopathological and immunohistochemical staining characteristics suggest that T1-T2 glottic and supraglottic LSCC should be considered as different entities.

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Section: Discussionmentioning

confidence: 99%

Distinct Biomarker Profiles and Clinical Characteristics in T1‐T2 Glottic and Supraglottic Carcinomas

et al. 2020

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“…Several candidates of molecular markers are also awaiting confirmation (p53, bclx, EGF, etc.) [ 68 ].…”

Section: Discussionmentioning

confidence: 99%

Radiotherapy for locally advanced resectable T3–T4 laryngeal cancer—does laryngeal preservation strategy compromise survival?

Yamazaki

Suzuki

Nakamura

et al. 2017

Journal of Radiation Research

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With the advancement of chemotherapy, a laryngeal preservation (LP) strategy was explored with the aim of improving maintenance of quality of life. Induction chemotherapy (ICT) following radiotherapy (RT) was considered a viable option because of its high initial response rate without hampering of overall survival (OS). Subsequently, concurrent chemoradiotherapy (CCRT) using CDDP became the standard of care for LP, showing the best LP ratio. For enhancing treatment intensity, ICT with taxan + CDDP + 5-FU (TPF-ICT) followed by RT showed superiority over ICT with CDDP + 5-FU (PF-ICT) followed by RT. Given that almost all randomized controlled trials investigating ICT include not only operable (endpoint, LP) but also inoperable (endpoint, OS) cases, physicians are faced with a dilemma regarding application in daily practice. In addition, increased treatment intensity causes augmentation of adverse events, which might reduce compliance. Thereafter, cetuximab, an effective drug with fewer adverse effects [bioradiotherapy (BRT)], emerged as another option. However, little evidence has confirmed its superiority over RT (or CCRT) in laryngeal cancer subpopulations. In spite of these developments, the OS of patients with laryngeal cancer has not improved for several decades. In fact, several studies indicated a decrease in OS during the 1990s, probably due to overuse of CCRT. Fortunately, the latter was not the case in most institutions. Currently, no other treatment has better OS than surgery. The eligibility criteria for LP and/or surgery largely depend upon the available expertise and experience, which differ from one institution to another. Therefore, a multidisciplinary team is required for the treatment of LP.

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“…Transmembrane epidermal growth factor receptor (EGFR), whose overactivation leads to uncontrolled cell division, is commonly overexpressed in HNSCC and has been associated with poor outcomes of radiation therapy . EGFR expression, however, has also been associated with improved outcomes of treatment employing altered fractionation regimens with shorter overall treatment duration …”

Section: Introductionmentioning

confidence: 99%

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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Effective Biomarkers and Radiation Treatment in Head and Neck Cancer

Abstract: Several potential biomarkers are actively being studied as predictors and targets to improve the use and efficacy of radiation therapy to treat head and neck squamous cell carcinoma. Several promising candidates have been defined, and new markers are on the horizon.

Cited by 13 publications

References 128 publications

Distinct Biomarker Profiles and Clinical Characteristics in T1‐T2 Glottic and Supraglottic Carcinomas

Distinct Biomarker Profiles and Clinical Characteristics in T1‐T2 Glottic and Supraglottic Carcinomas

Radiotherapy for locally advanced resectable T3–T4 laryngeal cancer—does laryngeal preservation strategy compromise survival?

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

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