Head and neck squamous cell carcinoma

Distant Metastases in Head-and-Neck Squamous Cell Carcinoma Treated with Intensity-modulated Radiotherapy

Source: International Journal of Radiation Oncology, Biology and Physics (IJROBP Online) December 2011 PURPOSE: To determine the pattern and risk factors for distant metastases in head-and-neck squamous cell carcinoma (HNSCC) after curative treatment with intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS: This was a retrospective study of 284 HNSCC patients treated in a single institution with IMRT. Sites included were oropharynx (125), oral cavity (70), larynx (55), hypopharynx (17), and unknown primary (17). American Joint Committee on Cancer stage distribution includes I (3), II (19), III (42), and IV (203). There were 224 males and 60 females with a median age of 57. One hundred eighty-six patients were treated with definitive IMRT and 98 postoperative IMRT. One hundred forty-nine patients also received concurrent cisplatin-based chemotherapy. RESULTS: The median follow-up for all patients was 22.8 months (range, 0.07-77.3 months) and 29.5 months (4.23-77.3 months) for living patients. The 3-year local recurrence-free survival, regional recurrence-free survival, locoregional recurrence-free survival, distant metastasis-free survival, and overall survival were 94.6%, 96.4%, 92.5%, 84.1%, and 68.95%, respectively. There were 45 patients with distant metastasis. In multivariate analysis, distant metastasis was strongly associated with N stage (p = 0.046), T stage (p<0.0001), and pretreatment maximum standardized uptake value of the lymph node (p = 0.006), but not associated with age, gender, disease sites, pretreatment standardized uptake value of the primary tumor, or locoregional control. The freedom from distant metastasis at 3 years was 98.1% for no factors, 88.6% for one factor, 68.3% for two factors, and 41.7% for three factors (p <0.0001 by log-rank [...]

Oral Cancer Foundation News Team - A2011-12-27T12:48:17-07:00December, 2011|Oral Cancer News|

A Planned Neck Dissection is Not Necessary in All Patients with N2-3 Head-and-Neck Cancer After Sequential Chemoradiotherapy

Source: DocGuide.com PURPOSE: To assess the role of a planned neck dissection (PND) after sequential chemoradiotherapy for patients with head-and-neck cancer with N2-N3 nodal disease. METHODS AND MATERIALS: We reviewed 90 patients with N2-N3 head-and-neck squamous cell carcinoma treated between 1991 and 2001 on two sequential chemoradiotherapy protocols. All patients received induction and concurrent chemotherapy with cisplatin and 5-fluorocuracil, with or without tirapazamine. Patients with less than a clinical complete response (cCR) in the neck proceeded to a PND after chemoradiation. The primary endpoint was nodal response. Clinical outcomes and patterns of failure were analyzed. RESULTS: The median follow-up durations for living and all patients were 8.3 years (range, 1.5-16.3 year) and 5.4 years (range, 0.6-16.3 years), respectively. Of the 48 patients with nodal cCR whose necks were observed, 5 patients had neck failures as a component of their recurrence [neck and primary (n = 2); neck, primary, and distant (n = 1); neck only (n = 1); neck and distant (n = 1)]. Therefore, PND may have benefited only 2 patients (4%) [neck only failure (n = 1); neck and distant failure (n = 1)]. The pathologic complete response (pCR) rate for those with a clinical partial response (cPR) undergoing PND (n = 30) was 53%. The 5-year neck control rates after cCR, cPR→pCR, and cPR→pPR were 90%, 93%, and 78%, respectively (p = 0.36). The 5-year disease-free survival rates for the cCR, cPR→pCR, and cPR→pPR groups were 53%, 75%, and 42%, respectively (p = 0.04). CONCLUSION: In our [...]

Oral Cancer Foundation News Team - A2011-12-13T10:52:02-07:00December, 2011|Oral Cancer News|

New Therapies and Prognostic Techniques Highlighted in Head and Neck Cancer

The Asco Post D. Neil Hayes, MD, MPH, of the University of North Carolina at Chapel Hill, described efforts to position the epidermal growth factor receptor (EGFR) inhibitor cetuximab (Erbitux) in head and neck cancer treatment. Surprisingly negative results came from the phase III Radiation Therapy Oncology Group (RTOG) 0522 trial (N = 940), which showed no benefit to adding cetuximab to the radiation/cisplatin platform for front-line therapy of advanced head and neck squamous cell carcinoma.1 At 2 years, progression-free survival was approximately 64% in both arms; overall survival was 79.7% with chemoradiation (P = .68) and 82.6% with the addition of cetuximab (P = .17). Rates of locoregional relapse and distant metastases were also similar. Cetuximab increased grade 3/4 mucositis (43% vs 33%;P < .004), in-field skin toxicity (25% vs 15%;P < .001), and out-of-field skin reactions (19% vs 1%;P < .001), but toxicity beyond 90 days was similar between the arms. "RTOG 0522 was the study of the year in head and neck cancer. Unfortunately, it was flat-out negative," Dr. Hayes noted. No differential effect emerged by p16 (HPV status). "While 70% of patients had oropharynx tumors (suggesting HPV positivity), tissue collection was lacking in half the patients. Our ability to make inferences with this amount of missing data is very limited," Dr. Hayes said. Even as a negative study, RTOG 0522 is practice-changing. "Many physicians have been treating with this regimen, assuming this study would be positive," he said. "But we now have no data to support this." Cetuximab Equivalent [...]

Oral Cancer Foundation News Team - A2011-10-18T09:58:29-07:00October, 2011|Oral Cancer News|

Palifermin Decreases Severe Oral Mucositis of Patients Undergoing Postoperative Radiochemotherapy for Head and Neck Cancer: A Randomized, Placebo-Controlled Trial

Source: OncologyStat.com TAKE-HOME MESSAGE This randomized, placebo-controlled trial found that weekly palifermin was associated with decreased incidence and duration of severe oral mucositis in patients undergoing postoperative chemoradiotherapy for head and neck cancer. SUMMARY OncologySTAT Editorial Team Combined chemoradiotherapy (CRT) offers improved outcomes after resection of locally advanced head and neck cancer but also increases the risk of oral mucositis, a debilitating and potentially dose-limiting toxicity of locoregional treatment. Palifermin, an analogue of keratinocyte growth factor, is FDA approved to prevent and treat mucositis in patients undergoing high-dose myelotoxic therapy for hematologic malignancies. In this multicenter, randomized, placebo-controlled trial, Henke et al evaluated whether palifermin reduces severe oral mucositis in patients undergoing CRT after surgical resection of locally advanced head and neck cancer. Adult patients receiving postoperative CRT for high-risk stage II to IVB head and neck squamous cell carcinoma and with an ECOG performance status of 0 to 2 were enrolled from 38 centers in Europe, Australia, and Canada. Eligible study patients were stratified by tumor location (oral cavity/oropharynx or hypopharynx/larynx) and residual tumor (R0 [complete resection] or R1 [incomplete resection]). Study patients received a radiation dose of 60 Gy (R0 group) or 66 Gy (R1 group) plus cisplatin 100 mg/m2 on days 1 and 22, with the study drug administered 3 days prior to starting CRT and then weekly for 6 weeks. Patients who underwent radiotherapy after 6 weeks received an additional 100 mg/m2 of cisplatin and study drug. Oral saline rinses, topical anesthetics, feeding tubes, and hematopoietic [...]

Oral Cancer Foundation News Team - A2011-09-20T10:21:43-07:00September, 2011|Oral Cancer News|

Cellular p16 localization and survival outcomes in head and neck cancer.

Source: ASCO.org Background: Head and neck squamous cell carcinoma (HNSCC) constitutes approximately 3-5 percent of all cancers. Recent data suggest an increasing incidence rate among younger people who are often non-smokers and non-drinkers, which are believed to be caused by human papillomavirus (HPV) infection. HPV positive tumors are typically found in the oropharynx and have better response to treatment and better disease outcome despite more advanced nodal stages. Therefore, HPV-positive HNSCCs represent a unique clinical subgroup with a separate tumor entity. Methods: Patients treated for HNSCC from 2002 to 2006 at UNC hospitals and had banked tissue available were eligible for this study. Tissue microarrays (TMA) were generated in triplicate. Immunohistochemical (IHC) staining for p16 was performed and scored separately for nuclear staining and cytoplasmic staining. Human papilloma virus (HPV) staining was also carried out using monoclonal antibody E6H4. P16 expression, HPV status and other clinical features were correlated with progression-free (PFS) and overall survival (OS). Results: 135 patients had sufficient sample for this analysis. Median age of diagnosis was 57 years (range 20-82), with 68.9% males, 8.9% never smokers and 32.6 % never drinkers. 3 year OS rate and PFS rate was 63.0% and 54.1% respectively. Based on the p16 staining score, patients were divided into three groups: high nuclear any cytoplasmic staining group (HNAC), low nuclear low cytoplasmic staining group (LNLC) and low nuclear high cytoplasmic staining group (LNHC). HNAC and LNLC groups had significantly better overall survival than LNHC groups with hazard ratios of 0.01 and 0.37 [...]

Oral Cancer Foundation News Team - A2011-06-03T12:35:21-07:00June, 2011|Oral Cancer News|

DNA repair biomarker profiling of head and neck vancer: Ku80 rxpression predicts locoregional failure and death following radiotherapy

Source: American Association for Cancer Research Abstract Purpose: Radiotherapy plays an integral role in the treatment of head and neck squamous cell carcinoma (HNSCC). Although proteins involved in DNA repair may predict HNSCC response to radiotherapy, none has been validated in this context. We examined whether differential expression of double-strand DNA break (DSB) repair proteins in HNSCC, the chief mediators of DNA repair following irradiation, predict for treatment outcomes. Experimental Design: Archival HNSCC tumor specimens were assembled onto a tissue microarray and stained with antibodies raised against 38 biomarkers. The biomarker set was enriched for proteins involved in DSB repair, in addition to established mechanistic markers of radioresistance. Staining was correlated with treatment response and survival alongside established clinical and pathologic covariates. Results were validated in an independent intramural cohort. Results: Ku80, a key mediator of DSB repair, correlated most closely with clinical outcomes. Ku80 was overexpressed in half of all tumors, and its expression was independent of all other covariates examined. Ku80 overexpression was an independent predictor for both locoregional failure and mortality following radiotherapy. The predictive power of Ku80 overexpression was confined largely to HPV-negative HNSCC, where it conferred a nine-fold greater risk of death at two years. Conclusions: Ku80 overexpression is a common feature of HNSCC, and is a candidate DNA repair-related biomarker for radiation treatment failure and death, particularly in patients with high-risk HPV-negative disease. It is a promising, mechanistically rational biomarker to select individual HPV-negative HNSCC patients for strategies to intensify treatment. Clin Cancer Res; [...]

Oral Cancer Foundation News Team - A2011-04-03T09:28:48-07:00March, 2011|Oral Cancer News|

Cetuximab therapy for head and neck squamous cell carcinoma: a systematic review of the data

Source: http://oto.sagepub.com/ Authors: Travis D. Reeves, MD et al. Objective: To review the current state of the data on the use of cetuximab in head and neck squamous cell carcinoma (HNSCC). Data Sources: The National Center for Biotechnology Information’s PubMed and the Cochrane collection. Review Methods. Search terms included cetuximab and head and neck cancer. These results were reviewed, and a second search was performed using limits: meta-analysis, randomized controlled trial, and clinical trial. Results: The literature search yielded 412 articles. Fifteen were identified for analysis. For patients with recurrent/metastatic disease who received combination chemotherapy in phase I/II trials, the overall response (OR) was 18.7% (95% confidence interval [CI], 10.4%-27.0%). Phase III trial data for combination chemotherapy in recurrent/metastatic disease showed OR to be 17.0% (95% CI, 12.6%-21.4%) for platinum-based regimens and 34.2% (28.6%-39.7%) for platinum-based regimens with cetuximab. For this same group, the estimated aggregate hazard ratio comparing platinum-based therapy plus cetuximab to platinum therapy alone was 1.10 (95% CI, 0.78-1.54), indicating no significant improvement in overall survival in the aggregate analysis. Combination chemoradiation with cetuximab in both phase I/II trials and the single phase III trial shows enhanced responsiveness, but the data are difficult to interpret because it is not used with standard-of-care regimens for advanced-stage disease. Conclusion: Early evidence has shown cetuximab to be effective in the treatment of HNSCC, and it should be used to enhance, but not replace, current treatment paradigms until further phase III data are available. Note: This article was presented at the [...]

Oral Cancer Foundation News Team - A2011-03-05T12:32:58-07:00March, 2011|Oral Cancer News|

Histopathologic findings of HPV and p16 positive HNSCC

Source: PubMed.gov OBJECTIVE: Human papilloma virus (HPV) and p16INKa (p16) positivity in head and neck squamous cell carcinomas (HNSCCs) is currently thought to be an encouraging prognostic indicator. However, the histopathologic changes responsible for this behavior are poorly understood. It is our objective to elucidate these histopathologic characteristics to help define the clinical utility of these markers. DESIGN: Retrospective cohort study. METHODS: 71 HNSCC tumors between July 1, 2008 and August 30, 2009 were examined for HPV, p16, and epidermal growth factor receptor (EGFR). Specified pathologic features were examined: perivascular invasion (PVI), perineural invasion (PNI), grade of squamous differentiation, basaloid classification. RESULTS: HPV and p16 had no direct impact on perineural or perivascular invasion. However, HPV and p16 were strongly predictive of poorly differentiated tumors, as well as basaloid squamous cell carcinoma (SCCA) (P < .001). Additionally, upon multivariate analysis, HPV(+) and p16(+) tumors had an increased risk of nodal metastasis (HPV: odds ratio [OR] = 23.9 (2.2, 265.1) p = .01; p16: OR = 6.5 (1.4, 31.2) p = .02; PVI: OR = 6.0 (1.6, 22.8) p < .01). The area under the curve (AUC) of receiver operating characteristic (ROC) curves demonstrated improved predictive value for lymph node metastasis above standard H&E histopathologic features (76.7%) for both HPV (83.2%) and p16 (81.3%) individually. CONCLUSIONS: HPV(+) and p16(+) are highly predictive for poorly differentiated tumors and basaloid SCCA. Additionally, HPV and p16 positivity demonstrate superior predictive value for lymph node metastasis above standard H&E histopathologic features. Although exact recommendations should be tempered by considerations of [...]

Oral Cancer Foundation News Team - A2010-11-08T13:31:34-07:00November, 2010|Oral Cancer News|

Nuances in the changing epidemiology of head and neck cancer

Source: Cancer Network Author: Daniel C. Beachler, MHS Head and neck squamous cell carcinoma (HNSCC) represents a heterogeneous group of malignancies caused by the traditional risk factors of tobacco, alcohol, and poor oral hygiene, as well as more recently identified roles of human papillomavirus (HPV) and Epstein-Barr virus (EBV).[1-3] We commend Kim and colleagues on their comprehensive review of the epidemiology of HNSCC. There has been a clear change in the epidemiology of HNSCC which has further accentuated differences in etiology, survival, and demographics among HNSCC patients. We will discuss several important nuances of this changing epidemiology, including the role of tobacco, race, sexual behavior, and gender, as well as HNSCC in nonsmokers and nondrinkers. As tobacco use has declined over the past several decades,[4,5] so has the number of cancers caused by tobacco and alcohol.[1,6,7] Continued decline in tobacco use and associated HNSCC is not guaranteed, however; in fact, some recent evidence suggests rates of tobacco use in the US may be stabilizing.[5] In contrast, the incidence of HPV-associated HNSCC has increased over the past several decades,[7] although it is unclear what is driving this change. The increasing incidence of HPV-associated HNSCC could be related to changes in oral sexual practices resulting in more oral HPV infection, or it may be explained by increased persistence and progression due to changes in relevant cofactors. Kim and colleagues noted in their review that HPV-associated HNSCC largely occurs among nonsmokers and nondrinkers. While it is true that HNSCC patients with HPV-associated disease [...]

Charlotte Parker2010-09-30T12:46:32-07:00September, 2010|Oral Cancer News|

Searching for molecular markers in head and neck squamous cell carcinomas (HNSCC) by statistical and bioinformatic analysis of larynx-derived SAGE libraries

Source: BMC Medical Genomics 2008, 1:56 (11 November 2008) Authors: Nelson JF Silveira et al. Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignancies in humans. The average 5-year survival rate is one of the lowest among aggressive cancers, showing no significant improvement in recent years. When detected early, HNSCC has a good prognosis, but most patients present metastatic disease at the time of diagnosis, which significantly reduces survival rate. Despite extensive research, no molecular markers are currently available for diagnostic or prognostic purposes. Methods: Aiming to identify differentially-expressed genes involved in laryngeal squamous cell carcinoma (LSCC) development and progression, we generated individual Serial Analysis of Gene Expression (SAGE) libraries from a metastatic and non-metastatic larynx carcinoma, as well as from a normal larynx mucosa sample. Approximately 54,000 unique tags were sequenced in three libraries. Results: Statistical data analysis identified a subset of 1,216 differentially expressed tags between tumor and normal libraries, and 894 differentially expressed tags between metastatic and non-metastatic carcinomas. Three genes displaying differential regulation, one down-regulated (KRT31) and two up-regulated (BST2, MFAP2), as well as one with a non-significant differential expression pattern (GNA15) in our SAGE data were selected for real-time polymerase chain reaction (PCR) in a set of HNSCC samples. Consistent with our statistical analysis, quantitative PCR confirmed the upregulation of BST2 and MFAP2 and the downregulation of KRT31 when samples of HNSCC were compared to tumor-free surgical margins. As expected, GNA15 presented a non-significant differential expression pattern when tumor samples [...]

Oral Cancer Foundation News Team - A2008-11-12T08:10:45-07:00November, 2008|Oral Cancer News|