Publications (8)38.13 Total impact
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Article: Metastatic head and neck cutaneous squamous cell carcinoma: defining a low-risk patient.
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ABSTRACT: The purpose of this study was to determine whether there is a "low-risk" subset of patients with regional metastatic head and neck cutaneous squamous cell carcinoma (SCC) suitable for treatment with surgery alone and omission of adjuvant radiotherapy. We conducted a retrospective analysis of 168 patients with a single parotid gland or neck nodal metastasis ≤3 cm in size from cutaneous SCC treated with curative intent by surgery ± adjuvant radiotherapy. Disease-specific survival for the 33 patients treated with surgery alone was 97% at 5 years. In the subset of 19 patients without extracapsular nodal spread (ECS), there was 1 regional recurrence which was successfully salvaged yielding a 5-year disease-specific survival of 100%. In head and neck cutaneous SCC, the subset with a single node ≤3 cm in size without ECS are at low risk of regional failure and death from cutaneous cancer. These patients may be suitable for single-modality therapy with surgery alone.Head & Neck 04/2011; 34(3):365-70. · 2.40 Impact Factor -
Article: Use of cyclin D1 in conjunction with human papillomavirus status to predict outcome in oropharyngeal cancer.
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ABSTRACT: There is increasing use of multiple molecular markers to predict prognosis in human cancer. Our aim was to examine the prognostic significance of cyclin D1 and retinoblastoma (pRb) expression in association with human papillomavirus (HPV) status in oropharyngeal squamous cell carcinoma. Clinical records and specimens of 226 patients with follow-up from 1 to 235 months postdiagnosis were retrieved. Tumor HPV status was determined by HPV E6-targeted multiplex real-time PCR/p16 semiquantitative immunohistochemistry and cyclin D1 and pRb expression by semiquantitative immunohistochemistry. Determinants of recurrence and mortality hazards were modeled using Cox regression with censoring at dates of last follow-up. The HPV-positivity rate was 37% (91% type 16). HPV was a predictor of recurrence, an event (recurrence or death) and death after adjustment for clinicopathological variables. There were inverse relationships between HPV status and cyclin D1 and pRb. On univariate analysis, cyclin D1 predicted locoregional recurrence, event and death and pRb predicted event and death. Within the HPV-positive group, after adjusting for clinicopathological factors, patients with cyclin D1-positive cancers had up to a eightfold increased risk of poor outcome relative to those with cyclin D1-negative tumors. However, within the HPV-negative group, there was only a very small adjusted increased risk. A combination of pRb and HPV did not provide additional prognostic information. Our data provide the first evidence that a combination of HPV and cyclin D1 provides more prognostic information in oropharyngeal cancer than HPV alone. If findings are confirmed, treatment based on HPV and cyclin D1 may improve outcomes.International Journal of Cancer 04/2011; 128(7):1532-45. · 5.44 Impact Factor -
Article: Predicting the prognosis of oral squamous cell carcinoma after first recurrence.
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ABSTRACT: to describe the clinicopathologic features of oral squamous cell carcinoma in patients who develop locoregional recurrence of disease, to identify factors that predict prognosis in the subset of patients treated with salvage surgery, and to determine the adjusted effect of time to recurrence. cohort study. a head and neck cancer institute in Sydney, New South Wales, Australia. a total of 77 patients who underwent salvage surgery for oral squamous cell carcinoma that had been treated initially by surgery, radiotherapy, or surgery with postoperative radiotherapy. univariable and multivariable analysis of clinical and pathologic risk factors. median time to recurrence from initial treatment was 7.5 months (range, 0.9-143.9 mo), with 86% of recurrences occurring within the first 24 months. Surgical salvage was attempted in 77 patients who had experienced recurrence at the primary site (n = 39), ipsilateral neck (n = 27), and contralateral neck (n = 11). Time to recurrence, initial treatment modality, and site of failure were independent prognostic variables. the relationship of these prognostic variables displays a dynamic interaction. Initial combined-modality treatment and shorter time to recurrence were associated with worse outcome, while the effect of site of recurrence (local vs regional) was dependent on an interaction with the time to recurrence. The result of this interaction was that local recurrence was worse for those who experienced it early (eg, <6 mo after the initial treatment) and nodal recurrence was worse for those who experienced it late (eg, ≥ 6 mo after the intial treatment).Archives of otolaryngology--head & neck surgery 12/2010; 136(12):1235-9. · 1.92 Impact Factor -
Article: Lymph node ratio as an independent prognostic factor in oral squamous cell carcinoma.
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ABSTRACT: We aimed to validate the lymph node ratio (LNR) as an independent prognostic factor in oral squamous cell carcinoma (OSCC) and compare its utility with the current nodal staging system. We conducted a retrospective analysis of 313 patients with OSCC undergoing neck dissection. The LNR was adjusted by relevant covariates in a multivariable Cox regression model. LNR displaced conventional nodal staging and was shown to be an independent predictor of regional failure (p = .020), disease-specific (p = .003) and overall survival (p = .001). Patients with an LNR of 2.5% to 7.5%, 7.5% to 20%, and >20% had 2.6, 3.7, and 4.4 times the risk of death from OSCC, respectively, when compared with patients with an LNR <2.5%. The LNR is an independent prognostic factor in OSCC and may be used in conjunction with the current TNM staging to enable better risk stratification and selection for adjuvant therapy.Head & Neck 10/2010; 33(9):1245-51. · 2.40 Impact Factor -
Article: Predicting the pattern of regional metastases from cutaneous squamous cell carcinoma of the head and neck based on location of the primary.
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ABSTRACT: We aimed to analyze the distribution of regional nodal metastases according to primary tumor location in patients with cutaneous squamous cell carcinoma of the head and neck (SCCHN). Analysis of 295 neck dissections performed for patients with clinically evident regional metastases from cutaneous SCCHN between 1987 and 2009. Level I involvement in the absence of level II or III only occurred in patients with facial primaries. In patients with clear nodes in level II-III, the risk of level IV-V involvement was 0.0% for external ear primaries, 2.7% for face and anterior scalp, and 15.8% for posterior scalp and neck. In patients undergoing parotidectomy for metastatic cutaneous SCCHN with a clinically negative neck, the results of this study support selective neck dissection including level I-III for facial primaries, level II-III for anterior scalp and external ear primaries, and levels II-V for posterior scalp and neck primaries.Head & Neck 10/2010; 32(10):1288-94. · 2.40 Impact Factor -
Article: Squamous cell carcinoma of the oropharynx in Australian males induced by human papillomavirus vaccine targets.
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ABSTRACT: This study provides Australian data on the incidence of human papillomavirus (HPV)-related oropharyngeal cancer to aid the debate on extending the HPV vaccination programme to males. The HPV status for 302 oropharyngeal cancers diagnosed between 1987 and 2006 was determined by HPV E6-targeted multiplex real-time PCR/p16 immunohistochemistry. The overall HPV-positivity rate was 36% (94% types 16 and 18). HPV-related cancer increased from 19% (1987-1990) to 47% (2001-2005). HPV data used in conjunction with Australian cancer incidence data 2001-2005 showed that 1.56 cases of oropharyngeal cancer per 100,000 males per year were associated with HPV types targeted by the vaccine. Vaccinating males may substantially reduce the burden of oropharyngeal cancer in Australia.Vaccine 03/2010; 28(19):3269-72. · 3.77 Impact Factor -
Article: Characterization of childhood acute lymphoblastic leukemia xenograft models for the preclinical evaluation of new therapies.
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ABSTRACT: Continuous xenografts from 10 children with acute lymphoblastic leukemia (ALL) were established in nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. Relative to primary engrafted cells, negligible changes in growth rates and immunophenotype were observed at second and third passage. Analysis of clonal antigen receptor gene rearrangements in 2 xenografts from patients at diagnosis showed that the pattern of clonal variation observed following tertiary transplantation in mice exactly reflected that in bone marrow samples at the time of clinical relapse. Patients experienced diverse treatment outcomes, including 5 who died of disease (median, 13 months; range, 11-76 months, from date of diagnosis), and 5 who remain alive (median, 103 months; range, 56-131 months, following diagnosis). When stratified according to patient outcome, the in vivo sensitivity of xenografts to vincristine and dexamethasone, but not methotrexate, differed significantly (P =.028, P =.029, and P =.56, respectively). The in vitro sensitivity of xenografts to dexamethasone, but not vincristine, correlated significantly with in vivo responses and patient outcome. This study shows, for the first time, that the biologic and genetic characteristics, and patterns of chemosensitivity, of childhood ALL xenografts accurately reflect the clinical disease. As such, they provide powerful experimental models to prioritize new therapeutic strategies for future clinical trials.Blood 06/2004; 103(10):3905-14. · 9.90 Impact Factor -
Article: The nonobese diabetic/severe combined immunodeficient (NOD/SCID) mouse model of childhood acute lymphoblastic leukemia reveals intrinsic differences in biologic characteristics at diagnosis and relapse.
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ABSTRACT: Acute lymphoblastic leukemia cells from 19 children, including 7 who remain in first complete remission (CR1), were engrafted into nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. High-level infiltration of bone marrow, spleen, and liver was observed, with variable infiltration of other organs. The immunophenotypes of xenografts were essentially unaltered compared with the original patient sample. In addition, sequencing of the entire p53 coding region revealed no mutations in 14 of 14 xenografts (10 from patients at diagnosis and 4 at relapse). Cells harvested from the spleens of engrafted mice readily transferred the leukemia to secondary and tertiary recipients. To correlate biologic characteristics of xenografts with clinical and prognostic features of the patients, the rates at which individual leukemia samples engrafted in NOD/SCID mice were analyzed. Differences in biologic correlates were encountered depending on stage of disease: a direct correlation was observed between the rate of engraftment and length of CR1 for samples harvested at relapse (r = 0.96; P =.002), but not diagnosis (r = 0.38; P =.40). In contrast, the in vivo responses of 6 xenografts to vincristine showed a direct correlation (r = 0.96; P =.002) between the length of CR1 and the rate at which the leukemia cell population recovered following vincristine treatment, regardless of whether the xenografts were derived from patients at diagnosis or relapse. This study supports previous findings that the NOD/SCID model of childhood ALL provides an accurate representation of the human disease and indicates that it may be of value to predict relapse and design alternative treatment strategies in a patient-specific manner.Blood 07/2002; 99(11):4100-8. · 9.90 Impact Factor
