Prognostic significance of p16 in locoregionally advanced head and neck cancer treated with concurrent 5-fluorouracil, hydroxyurea, cetuximab and intensity-modulated radiation therapy

Tong, Charles; Lau, Kenneth; Rivera, Michael; Cannan, David; Aguirre‐Ghiso, Julio A.; Sikora, Andrew G.; Gupta, Vishal; Forsythe, Kevin; Ko, Eric C.; Misiukiewicz, Krzysztof; Gurudutt, Vivek V.; Teng, Marita S.; Genden, Eric M.; Kao, Johnny

doi:10.3892/or.2012.1679

Cited by 5 publications

(9 citation statements)

References 31 publications

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“…The incidence of acute and late side effects after definitive RCT of HNSCC varies in the published studies, but severe grade 3/4 toxicities are described in 40-87% of cases [3,5,9]. Until now, acute and chronic skin reactions, mucositis, dysphagia and xerostomia have been the main sources of treatment-related morbidity.…”

Section: Discussionmentioning

confidence: 99%

“…Modern high-dose treatment techniques like IMRT/RapidArc have been shown to improve local control and clinical results [3,5,7,9], but toxicity remains a serious concern [8]. …”

Section: Discussionmentioning

confidence: 99%

“…Besides risk factors such as tobacco or alcohol, HPV infection was recognized as a carcinogenic factor with a wide spectrum of epithelial lesions such as oropharyngeal cancer. Several studies have demonstrated an improved overall survival (OS) of patients with p16 INK4A (p16)-expressing tumors, and p16 expression has been shown to be a suitable surrogate marker for the presence of HPV [2,3]. …”

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%

“…Modern high-dose treatment techniques like IMRT/RapidArc have been shown to improve local control and clinical results [3,5,7,9], but toxicity remains a serious concern [8]. …”

Section: Discussionmentioning

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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“…The addition of cetuximab to cisplatin-based CRT in patients with LA-SCCHN was demonstrated to be feasible 37–41. Efficacy data in Phase II trials were promising.…”

Section: Efficacy Studies Including Any Comparative Studiesmentioning

confidence: 99%

Cetuximab: its unique place in head and neck cancer treatment

Specenier¹,

Vermorken²

2013

BTT

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Head and neck cancer is the sixth most common cancer worldwide. At present, globally about 650,000 new cases of squamous cell carcinoma of the head and neck (SCCHN) are diagnosed each year. The epidermal growth factor receptor (EGFR) is almost invariably expressed in SCCHN. Overexpression of the EGFR is a strong and independent unfavorable prognostic factor in SCCHN. Cetuximab is a chimeric monoclonal antibody, which binds with high affinity to the extracellular domain of the human EGFR, blocking ligand binding, resulting in inhibition of the receptor function. It also targets cytotoxic immune effector cells towards EGFR-expressing tumor cells (antibody dependent cell-mediated cytotoxicity). The addition of cetuximab to radiotherapy (RT) improves locoregional control and survival when compared to RT alone. The addition of cetuximab to platinum-based chemoradiation (CRT) is feasible but does not lead to an improved outcome. Cetuximab plus RT has never been compared prospectively to CRT, which therefore remains the standard treatment for patients with locoregionally advanced SCCHN for whom surgery is not considered the optimal treatment, provided they can tolerate CRT. The addition of cetuximab to platinum-based chemotherapy prolongs survival in patients with recurrent or metastatic SCCHN. The combination of a platinum-based regimen and cetuximab should be considered as the standard first line regimen for patients who can tolerate this treatment.

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“…Multiple phase III trials have obtained the same results; compared to radiotherapy alone, CCRT can significantly improve locoregional control and OS 17,25,26. Maguire et al19 have moved to weekly cisplatin dosing (30 mg/m 2 ) in their CCRT regimens for patients with locally advanced SCCHN, with 3-year LRFS and OS of 87% and 80%, respectively.…”

Section: Discussionmentioning

confidence: 94%

Efficacy of intensity-modulated radiotherapy combined with chemotherapy or surgery in locally advanced squamous cell carcinoma of the head-and-neck

Yang¹,

Diao²,

Shi³

et al. 2013

BTT

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ObjectivesLong-term locoregional control following intensity-modulated radiotherapy (IMRT) for locally advanced squamous cell carcinoma of the head-and-neck (SCCHN) remains challenging. This study aimed to assess the efficacy and toxicity of IMRT with and without chemotherapy or surgery in locally advanced SCCHN.Materials and methodsBetween January 2007 and January 2011, 61 patients with locally advanced SCCHN were treated with curative IMRT in the Department of Radiation Oncology, Xijing Hospital, Fourth Military Medical University; 28% underwent definitive IMRT and 72% postoperative IMRT, combined with simultaneous cisplatin-based chemotherapy in 58%. The mean doses of definitive and postoperative IMRT were 70.8 Gy (range, 66–74 Gy). Outcomes were analyzed using Kaplan–Meier curves. Acute and late toxicities were graded according to Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer radiation morbidity scoring criteria.ResultsAt a median follow-up of 35 months, 3-year local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) were 83.8%, 86.1%, 82.4%, 53.2%, and 62%, respectively. Postoperative IMRT (n = 44, 72%) had significantly higher LRFS/OS/DMFS than definitive IMRT (n = 17, 28%; P < 0.05). IMRT combined with chemotherapy (n = 35, 58%) had significantly higher LRFS/OS/DMFS than IMRT alone (n = 26, 42%; P < 0.05). One year after radiotherapy, the incidence of xerostomia of grade 1, 2, or 3 was 13.1%, 19.7%, and 1.6%, respectively. No grade 4 acute or late toxicity was observed.ConclusionIMRT combined with surgery or chemotherapy achieved excellent long-term locoregional control and OS in locally advanced SCCHN, with acceptable early toxicity and late side-effects.

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Prognostic significance of p16 in locoregionally advanced head and neck cancer treated with concurrent 5-fluorouracil, hydroxyurea, cetuximab and intensity-modulated radiation therapy

Cited by 5 publications

References 31 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

Cetuximab: its unique place in head and neck cancer treatment

Efficacy of intensity-modulated radiotherapy combined with chemotherapy or surgery in locally advanced squamous cell carcinoma of the head-and-neck

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