Applicability of randomized trials in radiation oncology to standard clinical practice.

BACKGROUND: Randomized controlled trials (RCTs) are commonly used to inform clinical practice; however, it is unclear how generalizable RCT data are to patients in routine clinical practice. The authors of this report assessed the availability and applicability of randomized evidence guiding medical decisions in a cohort of patients who were evaluated for consideration of definitive management in a radiation oncology clinic. METHODS: The medical records of consecutive, new patient consultations between January and March 2007 were reviewed. Patient medical decisions were classified as those with (Group 1) or without (Group 2) available, relevant level I evidence (phase 3 RCT) supporting recommended treatments. Group 1 medical decisions were further divided into 3 groups based on the extent of fulfilling eligibility criteria for each RCT: Group 1A included decisions that fulfilled all eligibility criteria; Group 1B, decisions that did not fulfill at least 1 minor eligibility criteria; or Group 1C, decisions that did not fulfill at least 1 major eligibility criteria. Patient and clinical characteristics were tested for correlations with the availability of evidence. RESULTS: Of the 393 evaluable patients, malignancies of the breast (30%), head and neck (18%), and genitourinary system (14%) were the most common presenting primary disease sites. Forty-seven percent of all medical decisions (n = 451) were made without available (36%) or applicable (11%) randomized evidence to inform clinical decision making. Primary tumor diagnosis was significantly associated with the availability of evidence (P < .0001). CONCLUSIONS: A significant proportion of medical decisions in an academic radiation oncology clinic were made without available or applicable level I evidence, underscoring the limitations of relying solely on RCTs for the development of evidence-based health care.

Review of the clinical and biologic aspects of human papillomavirus-positive squamous cell carcinomas of the head and neck.

Human papillomavirus (HPV), a known etiology of a subset of head-and-neck squamous cell carcinomas (HNCs), causes numerous alterations in normal cellular functions. This article reviews the biology, detection, and treatment of HPV-positive HNC. The role of HPV oncoproteins in tumor development, the natural history of HPV infection, and risk factors for and prevention of transmission of oral HPV are considered. Commonly used methods for detecting HPV infection, including limitations of these methods, are discussed to aid the practicing clinician in using these tests in their clinical practice. Clinical characteristics of HPV-positive HNC, including potential explanations for the improved outcomes seen in patients with HPV-positive HNC, are assessed. Ongoing clinical trials specific for patients with HPV-positive HNC are described, and areas in need of additional research are summarized. Until the results of ongoing trials are known, treatment of HPV-positive HNC should not differ in clinical practice from treatment of similar non-HPV related cancers.

ERCC1 protein expression is associated with differential survival in oropharyngeal head and neck squamous cell carcinoma.

OBJECTIVE: To investigate ERCC1 protein expression and its relationship to clinical factors and treatment outcomes in patients with head and neck squamous cell carcinoma (HNSCC). DESIGN: Case series. SETTING: Tertiary care academic center. SUBJECTS: One hundred and seventy-six patients diagnosed with HNSCC and treated with intent to cure between 2002 and 2008 were analyzed with respect to clinical data and tumor pathology. MAIN OUTCOME MEASURES: Tissue microarrays were constructed from tumor blocks and immunohistochemical staining for ERCC1 performed. ERCC1 expression status was dichotomized into high and low using the Allred score. Clinical characteristics of patients with high versus low ERCC1 expression were compared. Distributions of overall survival (OS) and progression-free survival (PFS) were analyzed using the Kaplan-Meier method. RESULTS: Of 176 patients, ERCC1 showed baseline nuclear staining in 148 patients (84.1%). Lower staining intensity ERCC1 expression was prominent in parabasal cells in the lower half of the epithelium, while at high staining intensity, ERCC1 expression was present throughout the epithelium. The median H-score was 50. No significant differences in age, gender, smoking status, tumor site, or stage were seen between the high and low ERCC1 expression groups. Expression of ERCC1 stratified by tumor site correlates with OS. Patients with oropharyngeal HNSCC and high ERCC1 expression (H-score > 120) were more likely to survive (P < .01) and remain disease free when compared to non-oropharyngeal squamous cell carcinoma (SCCa) patients with high ERCC1 expression despite treatment modality and human papillomavirus virus (HPV) status. CONCLUSION: Patients with oropharyngeal SCCa and high ERCC1 expression may have better outcomes despite HPV status.

Association of p16(INK4a) overexpression with improved outcomes in young patients with squamous cell cancers of the oral tongue.

BACKGROUND: The aim of this study was to examine biomolecular profiles in a cohort of young adults with squamous cell cancers (SCCs) of the oral tongue. METHODS: We identified all patients aged 18 to 39 years diagnosed with SCC of the oral tongue at our institution. Immunohistochemical (IHC) staining was performed for p16(INK4a) , epidermal growth factor receptor (EGFR), phosphorylated-EGFR (pEGFR), p53, and ERCC1. Human papillomavirus (HPV) testing was performed using in situ hybridization (ISH) and polymerase chain reaction (PCR). Biomarker expression and HPV status were correlated with outcomes. RESULTS: We identified 25 patients with sufficient tumor samples. Median age at diagnosis was 30 years (range, 20-39 years). p16(INK4a) overexpression was observed in 11 of 25 patients, whereas HPV-16 positivity was observed in none of the tumor samples by ISH and 2 of the tumor samples by PCR. p16(INK4a) positivity was correlated with improved relapse-free survival (hazard ratio [HR] = 0.23, p = .01) and overall survival (HR = 0.28, p = .05). Neither EGFR, pEGFR, p53, nor excision repair cross-complementing rodent repair deficiency, complementation group 1 (ERCC1) expression correlated with outcome on univariate analysis. CONCLUSIONS: p16(INK4a) overexpression was common and was a marker of favorable prognosis. p16(INK4a) overexpression was not a reliable predictor of HPV positivity in our cohort.

High XRCC1 protein expression is associated with poorer survival in patients with head and neck squamous cell carcinoma.

PURPOSE: We evaluated X-ray repair complementing defective repair in Chinese hamster cells 1 (XRCC1) protein in head and neck squamous cell carcinoma (HNSCC) patients in association with outcome. EXPERIMENTAL DESIGN: XRCC1 protein expression was assessed by immunohistochemical (IHC) staining of pretreatment tissue samples in 138 consecutive HNSCC patients treated with surgery (n = 31), radiation (15), surgery and radiation (23), surgery and adjuvant chemoradiation (17), primary chemoradiation (51), and palliative measures (1). RESULTS: Patients with high XRCC1 expression by IHC (n = 77) compared with patients with low XRCC1 expression (n = 60) had poorer median overall survival (OS; 41.0 months vs. OS not reached, P = 0.009) and poorer progression-free survival (28.0 months vs. 73.0 months, P = 0.031). This association was primarily due to patients who received chemoradiation (median OS of high- and low-XRCC1 expression patients, 35.5 months and not reached respectively, HR 3.48; 95% CI: 1.44-8.38; P = 0.006). In patients treated with nonchemoradiation modalities, there was no survival difference by XRCC1 expression. In multivariable analysis, high XRCC1 expression and p16(INK4a)-positive status were independently associated with survival in the overall study population (HR = 2.62; 95% CI: 1.52-4.52; P < 0.001 and HR = 0.21; 95% CI: 0.06-0.71; P = 0.012, respectively) and among chemoradiation patients (HR = 6.02; 95% CI: 2.36-15.37; P < 0.001 and HR = 0.26; 95% CI: 0.08-0.92, respectively; P = 0.037). CONCLUSIONS: In HNSCC, high XRCC1 protein expression is associated with poorer survival, particularly in patients receiving chemoradiation. Future validation of these findings may enable identification of HNSCC expressing patients who benefit from chemoradiation treatment.

Never-smokers, never-drinkers: unique clinical subgroup of young patients with head and neck squamous cell cancers.

BACKGROUND: Young patients represent an increasing subgroup with head and neck cancer. METHODS: Patients between 18 and 39 years of age with newly diagnosed and previously untreated squamous cell cancers were identified. RESULTS: Seventy-eight patients met the selection criteria: 28 patients were never-smokers/never-drinkers (NSNDs), and 50 patients reported tobacco or alcohol abuse (smokers and/or drinkers [SD]). NSND patients were diagnosed at a younger median age (31.5 years vs 35.5 years, p = .007), were more likely to be female (75% vs 30%, p < .001) and white (89% vs 60%, p = .006), and were more likely to have tumors of the oral tongue (57% vs 24%, p = .003) and T1 disease (47% vs 20%, p = .01). There was no difference in 10-year relapse-free survival, but a suggestion of improved 10-year overall survival for NSND patients (71% vs 46%, p = .10). CONCLUSIONS: Young patients with head and neck squamous cell carcinoma (HNSCC) appear to have unique clinical profiles based on history of alcohol and tobacco abuse.