Stephen Kleid

Planned neck dissection as an adjunct to the management of patients with advanced neck disease treated with definitive radiotherapy: For some or for all?

Management of patients with head and neck carcinoma and advanced nodal disease is controversial. The purpose of this analysis was to evaluate the efficacy and toxicity of definitive radiotherapy followed by planned neck dissection in patients with bulky neck disease.

Differential mechanisms of CDKN2A (p16) alteration in oral tongue squamous cell carcinomas and correlation with patient outcome.

CDKN2A (p16) disruption is reported as a frequent event in head and neck squamous cell carcinomas that confers poor prognosis. We investigated the frequency of different potential mechanisms of CDKN2A inactivation in oral tongue squamous cell carcinomas (OTSCC) and their impact on patient outcome. From a cohort of 153 OTSCC patients, 131 formalin fixed paraffin embedded blocks of pre‐treatment primary tumours were suitable for further molecular analysis. We assessed CDKN2A (p16) levels by immunohistochemistry (IHC), promoter methylation status by methylation‐sensitive high resolution melting, mutation status by Sanger sequencing, gene copy number variation by fluorescence in situ hybridisation, and correlated these with patient outcome. We found that the majority of OTSCC did not overexpress p16 (110/116, 95%), assessed by IHC. The frequency of CDKN2A mutations was 20% (21/103), homozygous loss was 7% (7/97), hemizygous loss 31% (30/97), and promoter methylation was 18% (20/113). We found no evidence of these mechanisms in 24/106 (23%) p16 IHC negative tumours. No significant correlation was identified between any potential mechanism of CDKN2A inactivation and clinical features, including smoking status and age. There was a non‐significant trend for worse overall survival for p16 IHC negative patients versus positive patients (HR = 1.81, 95% CI = 0.44–7.47, p = 0.40). No relationship was found between mechanisms of CDKN2A disruption and patient outcome. In conclusion, we demonstrate that CDKN2A alteration is a frequent event in OTSCC tumourigenesis. However, no correlation was identified between different potential mechanisms of CDKN2A disruption and clinical characteristics or patient outcome.

Prospective trial to evaluate staged neck dissection or elective neck radiotherapy in patients with CT-staged T1-2 N0 squamous cell carcinoma of the oral tongue.

A prospective study was undertaken to evaluate a policy of selective, single‐modality elective neck treatment in T1‐2, node‐negative oral tongue squamous cell carcinoma.

Safety of thromboprophylaxis after oncologic head and neck surgery. Study of 1018 patients.

Deep venous thrombosis (DVT) and pulmonary embolism (PE) are significantly reduced with appropriate use of thromboprophylaxis and scarcely evaluated in patients undergoing oncologic head and neck surgery (OHNS).

Frequency of Fibroblast Growth Factor Receptor 1 gene amplification in oral tongue squamous cell carcinomas and associations with clinical features and patient outcome

OBJECTIVES Novel therapies are required for patients with recurrent or metastatic oral tongue squamous cell carcinoma (OTSCC). Fibroblast Growth Factor Receptor 1 (FGFR1) amplification frequently occurs in squamous cell carcinoma of the lung and represents a novel druggable therapeutic target in this and other malignancies. This study examined the frequency and clinical associations of FGFR1 amplification in OTSCC. MATERIALS AND METHODS The frequency of FGFR1 amplification determined by fluorescence in situ hybridization was evaluated in a cohort of 123 OTSCC patients. Associations of FGFR1 amplification with clinical characteristics and outcome were determined. RESULTS FGFR1 gene amplification was present in 9.3% (10/107) of cases and was significantly associated with smoking status (P = 0.03). FGFR1 amplification was seen more commonly in males (9/10 amplified cases male, P = 0.16) and there were no associations with age, stage, T stage, nodal status, alcohol history or performance status (all P>0.05). Outcome was not significantly different between FGFR1 amplified and non-amplified patients. CONCLUSIONS Copy number variations of the FGFR1 gene occur in a subset of OTSCC with approximately 10% of cases showing amplification of the gene. FGFR1 amplification may represent a therapeutic target in OTSCC.

Quantitative methodology is critical for assessing DNA methylation and impacts on correlation with patient outcome

BackgroundDNA hypermethylation is reported as a frequent event and prognostic marker in head and neck squamous cell carcinomas (HNSCC). Methylation has been commonly assessed with non-quantitative methodologies, such as methylation-specific PCR (MSP). We investigated previously reported hypermethylated genes with quantitative methodology in oral tongue squamous cell carcinomas (OTSCC).ResultsThe methylation status of 12 genes in 115 OTSCC samples was assessed by one or more of three quantitative analyses: methylation sensitive high resolution melting (MS-HRM), sensitive-melting analysis after real time-methylation specific PCR (SMART-MSP), and bisulfite pyrosequencing.In contrast to much of the literature, either no or infrequent locus-specific methylation was identified by MS-HRM for DAPK1, RASSF1A, MGMT, MLH1, APC, CDH1, CDH13, BRCA1, ERCC1, and ATM. The most frequently methylated loci were RUNX3 (18/108 methylated) and ABO (22/107 methylated). Interrogation of the Cancer Genome Atlas (TCGA) HNSCC cohort confirmed the frequency of significant methylation for the loci investigated.Heterogeneous methylation of RUNX3 (18/108) and ABO (22/107) detected by MS-HRM, conferred significantly worse survival (P = 0.01, and P = 0.03). However, following quantification of methylation levels using pyrosequencing, only four tumors had significant quantities (>15%) of RUNX3 methylation which correlated with a worse patient outcome (P <0.001), while the prognostic significance of ABO hypermethylation was lost. RUNX3 methylation was not prognostic for the TCGA cohort (P = 0.76).ConclusionsWe demonstrated the critical need for quantification of methylation levels and its impact on correlative analyses. In OTSCC, we found little evidence of significant or frequent hypermethylation of many loci reported to be commonly methylated. It is likely that previous reports have overestimated the frequency of significant methylation events as a consequence of the use of non-quantitative methodology.

p16-positive lymph node metastases from cutaneous head and neck squamous cell carcinoma: No association with high-risk human papillomavirus or prognosis and implications for the workup of the unknown primary.

The incidence of p16 overexpression and the role of human papillomavirus (HPV) in cutaneous head and neck squamous cell carcinoma (cHNSCC) are unclear.

Squamous cell carcinoma arising in the skin of a deltopectoral flap 27 years after pharyngeal reconstruction

Development of a second primary squamous cell carcinoma in the skin of a flap used for pharyngeal reconstruction is rare.

Craniofacial resection in the management of paranasal sinus cancer.

Abstract The prognosis for patients with cancer of the paranasal sinuses (PNC) has been very poor, mainly due to a high rate of local recurrence. We report a series of 46 patients with PNC treated by craniofacial resection at the Royal Melbourne Hospital between November 1983 and June 1991. There has been no operative mortality or serious morbidity in these patients. The importance of a pericranial flap in the reconstruction of the floor of the anterior cranial fossa is emphasized. All patients have been followed to death or to the present time. There was a five year survival of 73% for squamous cell carcinoma and 83% for adenocarcinoma. This appears to represent a significant improvement in the long term results over conventional surgery and radiotherapy. The strong association between adenocarcinoma of the ethmoid sinuses and occupational exposure to hardwood dusts is borne out in our series. A history of prolonged wood dust exposure was given by all the 16 patients with adenocarcinoma and by 12 of the 25 patients with squamous cell carcinoma.

Malignant fibrous histiocytoma of the maxilla—a report of two cases

Two cases of malignant fibrous histiocytoma of the maxilla are reported. The tumours were excised via a combined temporal and intra-oral approach in order to gain adequate surgical access and minimise the aesthetic deformity. One patient required orbital exenteration.