Concurrent Chemotherapy and Radiotherapy for Organ Preservation in Advanced Laryngeal Cancer

Forastiere, Arlene A.; Goepfert, Helmuth; Maor, Moshe; Pajak, Thomas F.; Weber, Randal S.; Morrison, William H.; Glisson, Bonnie S.; Trotti, Andy; Ridge, John A.; Chao, C.; Peters, Glenn E.; Lee, Ding Jen; Leaf, Andrea; Ensley, John F.; Cooper, Jay S.

doi:10.1056/nejmoa031317

Cited by 2,753 publications

(2,254 citation statements)

References 10 publications

Supporting

Mentioning

2,059

Contrasting

Unclassified

Order By: Relevance

“…Finally, FADD expression and phosphorylation have been shown to affect cell cycle progression (Alappat et al, 2003) and resistance to chemotherapy (Shimada et al, 2004). Moreover, treatment with combinations of chemotherapy and radiation (Forastiere et al, 2003;Vermorken et al, 2007) might be affected by FADD expression due to 11q13 amplification, as hypothesized previously (Gibcus et al, 2007b). Because amplification was proven an early event in tumorigenesis (Izzo et al, 1998;Burnworth et al, 2006), and amplicons are inherited during tumorigenesis, we hypothesize that the high occurrence of 11q13.3 amplification enables multiple genes to be beneficial to tumour progression at distinct stages of tumour development.…”

Section: Discussion Cortactin Predicts Poor Survival In Late Stage Lamentioning

confidence: 99%

Cortactin expression predicts poor survival in laryngeal carcinoma

et al. 2008

View full text Add to dashboard Cite

Amplification of the 11q13 region is one of the most frequent aberrations in squamous cell carcinomas of the head and neck region (HNSCC). Amplification of 11q13 has been shown to correlate with the presence of lymph node metastases and decreased survival. The 11q13.3 amplicon carries numerous genes including cyclin D1 and cortactin. Recently, we reported that FADD becomes overexpressed upon amplification and that FADD protein expression predicts for lymph node positivity and disease-specific mortality. However, the gene within the 11q13.3 amplicon responsible for this correlation is yet to be identified. In this paper, we compared, using immunohistochemical analysis for cyclin D1, FADD and cortactin in a series of 106 laryngeal carcinomas which gene correlates best with lymph node metastases and increased disease-specific mortality. Univariate Cox regression analysis revealed that high expression of cyclin D1 (P ¼ 0.016), FADD (P ¼ 0.003) and cortactin (P ¼ 0.0006) predict for increased risk to disease-specific mortality. Multivariate Cox analysis revealed that only high cortactin expression correlates with disease-specific mortality independent of cyclin D1 and/or FADD. Of genes located in the 11q13 amplicon, cortactin expression is the best predictor for shorter diseasespecific survival in late stage laryngeal carcinomas. Current methods to predict the outcome of head and neck squamous cell carcinoma (HNSCC) patients mainly involve clinicopathological parameters such as tumour size, differentiation grade and presence of lymph node metastasis. Patients with laryngeal squamous cell carcinomas (LSCC) have not shown an increase in 5-year survival rates over the last 30 years (Almadori et al, 2005). Therefore, other parameters such as molecular markers that are able to more accurately predict the outcome of disease, are needed.A frequent molecular event in HNSCC is amplification of the 11q13 region (36%) (Schuuring, 1995;Freier et al, 2006). Amplification of this region in HNSCC has been associated with decreased survival (Akervall et al, 1995;Meredith et al, 1995), increased distant metastasis (Namazie et al, 2002) and lymph node metastasis (Chen et al, 2004;Hermsen et al, 2005;Xia et al, 2007). It is believed that amplification increases gene dosage and expression of genes within the amplified region (amplicon) (Albertson, 2006). Recently, we reported that the commonly amplified region is located at 11q13.3 and contains at least six genes (cyclin D1, TAOS1, FGF19, FADD, PPFIA1 and cortactin) that are overexpressed when amplified (Gibcus et al, 2007b). We concluded that the selection for tumour cells with the 11q13.3 amplicon during tumorigenesis could be based on the increased doses of one or more of these genes. We proposed FADD as a possible candidate for this selection, since FADD showed the best correlation between DNA amplification and increased expression (Gibcus et al, 2007b). Furthermore, FADD protein expression correlated with disease specific mortality (DSM) in a series of late stage laryngeal carcinom...

show abstract

Section: Discussion Cortactin Predicts Poor Survival In Late Stage Lamentioning

confidence: 99%

Cortactin expression predicts poor survival in laryngeal carcinoma

et al. 2008

View full text Add to dashboard Cite

show abstract

“…This site-specific difference may also be seen in the varied treatment approaches. While surgery and radiation therapy were once the only primary treatments offered, head and neck sites such as the larynx and oropharynx have seen a paradigm shift to chemotherapy and radiotherapy [4], while oral cavity tumors are still treated predominantly with surgery [3]. There is also a stage related difference in therapy, with early stage lesions often managed with single modality treatment and advanced stage disease treated with multimodality therapy.…”

Section: Introductionmentioning

confidence: 99%

Site-Specific Molecular Signatures Predict Aggressive Disease in HNSCC

Belbin

Smith

Adrien

et al. 2008

Head and Neck Pathol

View full text Add to dashboard Cite

It is known that head and neck squamous cell carcinomas (HNSCC) originating from different anatomic locations can exhibit varying behavior that is not predictable by histopathology of the primary tumor. Using a microarray containing 27,323 cDNA clones, we generated sets of gene expression profiles for 36 HNSCC primary tumors (12 oral cavity, 12 oropharynx, and 12 larynx/ hypopharynx). From these datasets, we ranked genes according to their ability to differentiate between patients whose disease progressed within a 24 month period (aggressive phenotype) and those that did not (nonaggressive phenotype) based on levels of gene expression. A merging of datasets from the three sites revealed that only a fraction of identified genes were shared between any two sites. This contrasted greatly with the significant overlap (approximately 50%) in down-regulated genes identified in tumor/normal comparisons using cases both from oropharynx and larynx/hypopharynx. From these data, we conclude that HNSCC tumors originating from different anatomic sites share consistent changes in gene expression when comparing primary tumors to normal adjacent mucosa; these common changes most likely reflect alterations required for tumor development. In contrast, once a tumor has developed, tumor-host interactions at the different anatomic sites are likely responsible for the site-specific signatures associated with aggressive versus non-aggressive disease. Predictions of outcome based on gene expression profiling are therefore heavily influenced by the anatomic site of the primary tumor.

show abstract

“…In up to 82% of the patients treated, toxic side-effects of grade 3 ("severe") to 4 ("life-threatening") were documented [123]. Other studies on simultaneous radiation therapy and chemotherapy reported toxicity of grades 3-4 for mucositis (53%), dysphagia (54%), and dermatitis (19%).…”

Section: Toxicitymentioning

confidence: 98%

Refinement of the free radial forearm flap reconstructive technique after resection of large oropharyngeal malignancies with excellent functional results

et al. 2003

View full text Add to dashboard Cite

Preservation of function is a crucial aspect for the evaluation of therapies applied in the field of head and neck cancer. However, preservation of Uta Tschiesner 1 anatomic structures cannot automatically be equated with preservation 1 Clinic for Otorhinolaryngology, Ludwig Maximilians of function. Functional outcome becomes increasingly important particularly for the evaluation of alternative treatment options with equivalent oncological outcomes.University (LMU) Munich, Munich, GermanyAs a result, present studies take into account three topic areas with varying emphasis: (1) the effects of cancer therapy on essential physiological functions, (2) additional therapy-induced side-effects and complications, and (3) health-related quality of life. The present article summarizes vital aspects of clinical research from recent years. Functional outcomes after surgical and non-surgical treatment approaches are presented according to tumor localization and staging criteria. Additional methodological aspects relating to data gathering and documentation as well as challenges in implementing the results in clinical practice are also discussed.

show abstract

Concurrent Chemotherapy and Radiotherapy for Organ Preservation in Advanced Laryngeal Cancer

Abstract: In patients with laryngeal cancer, radiotherapy with concurrent administration of cisplatin is superior to induction chemotherapy followed by radiotherapy or radiotherapy alone for laryngeal preservation and locoregional control.

Cited by 2,753 publications

References 10 publications

Cortactin expression predicts poor survival in laryngeal carcinoma

Cortactin expression predicts poor survival in laryngeal carcinoma

Site-Specific Molecular Signatures Predict Aggressive Disease in HNSCC

Refinement of the free radial forearm flap reconstructive technique after resection of large oropharyngeal malignancies with excellent functional results

Contact Info

Product

Resources

About