Christopher Milross

Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia

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Publications (16)56.41 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: This review examines the most commonly reported treatment options for ocular squamous cell carcinoma (OSCC) and periocular squamous cell carcinoma (POSCC) in horses and proposes to conclude on the most viable method based on available published studies in terms of treatment outcome, known side-effects, advantages, disadvantages, and reliability of available evidence. Following a literature search for peer-reviewed published articles, seven most commonly reported on treatments for OSCC/POSCC were identified: surgery, photodynamic therapy, carbon dioxide CO2 laser ablation, radiofrequency hyperthermia, cryotherapy, chemotherapy and radiation therapy. Combination therapies were supported as a most successful recommendation, however, when considering site-specific outcomes, the following conclusions may be drawn; limbal SCC was most effectively treated with surgery and adjunctive therapy including CO2 laser ablation, mitomycin C and brachytherapy; third eyelid SCC reported good outcomes when treated with surgery alone (clear margins) and in combination with brachytherapy for unclear margins; eyelid SCC, surgical resection was usually limited and most reports supported the use of adjunctive brachytherapy although photodynamic therapy appeared to be a promising new treatment. It was deemed unreasonable to conclude on the best treatment for cornea, conjunctivae (palpebral and bulbar) and medial canthi in isolation due to lack of evidence .A consistently favoured treatment for OSCC/POSCC in horses does not currently exist. The presentation of data in the literature and its lack of consistency make it impossible to statistically analyse and make comparative conclusions on treatment outcomes. This review provides a basis for further research to establish a best-practice protocol.
    Journal of Equine Veterinary Science 01/2014; · 0.62 Impact Factor
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    ABSTRACT: BACKGROUND AND PURPOSE: Human papillomavirus (HPV) causes up to 70 % of oropharyngeal cancers (OSCC). HPV positive OSCC has a more favorable outcome, thus HPV status is being used to guide treatment and predict outcome. Combination HPV DNA/p16(ink4) (p16) testing is commonly used for HPV status, but there are no standardized methods, scoring or interpretative criteria. The significance of discordant (HPV DNA positive/p16 negative and HPV DNA negative/p16 positive) cancers is controversial. In this study, 647 OSCCs from 10 Australian centers were tested for HPV DNA/p16 expression. Our aims are to determine p16 distribution by HPV DNA status to inform decisions on p16 scoring and to assess clinical significance of discordant cancers. METHODS: HPV DNA was identified using a multiplex tandem HPV E6 polymerase chain reaction (PCR) assay and p16 expression by semiquantitative immunohistochemistry. RESULTS: p16 distribution was essentially bimodal (42 % of cancers had ≥70 % positive staining, 52 % <5 % positive, 6 % between 5 and 70 %). Cancers with 5 to <50 % staining had similar characteristics to the p16 negative group, and cancers with 50 to <70 % staining were consistent with the ≥70 % group. Using a p16 cut-point of 50 %, there were 25 % HPV DNA positive/p16 negative cancers and 1 % HPV DNA negative/p16 positive cancers. HPV DNA positive/p16 negative cancers had outcomes similar to HPV DNA negative/p16 negative cancers. CONCLUSIONS: 50 % is a reasonable cut-point for p16; HPV DNA positive/p16 negative OSCCs may be treated as HPV negative for clinical purposes; HPV DNA/p16 testing may add no prognostic information over p16 alone.
    Annals of Surgical Oncology 12/2012; · 4.12 Impact Factor
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    ABSTRACT: It is now clear that the two separate entitles of tonsillar cancer, HPV induced and non-HPV induced (smoking induced), have significantly different presenting stage and outcomes. A significant proportion of patients with human papillomavirus positive tonsillar cancer have had exposure to smoking. We examined the combined effect of human papillomavirus and smoking on the outcomes and determined whether smoking can modify the beneficial effect of human papillomavirus. 403 patients from 9 centres were followed up for recurrence or death for a median of 38 months. Determinants of the rate of loco-regional recurrence, death from tonsillar cancer and overall survival were modelled using Cox regression. Smoking status was a significant predictor of overall survival (p=0.04). There were non-statistically significant trends favoring never smokers for loco-regional recurrence and disease specific survival. In addition, there was no statistically significant interactions between smoking and human papillomavirus (p-values for the interaction were 0.26 for loco-regional recurrence, 0.97 for disease specific survival and 0.73 for overall survival). The effect of smoking on loco-regional recurrence and disease specific survival outcomes was not statistically significant, nor was there significant evidence that the effect of smoking status on these outcomes was modified by HPV status. Irrespective of HPV status however, smokers did have poorer overall survival than never-smokers; presumably due to effects of smoking that are unrelated to the primary cancer. © 2012 Wiley Periodicals, Inc.
    International Journal of Cancer 11/2012; · 6.20 Impact Factor
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    ABSTRACT: Cancer is a common disease and radiotherapy is one well-established treatment for some solid tumours. Hyperbaric oxygenation therapy (HBOT) may improve the ability of radiotherapy to kill hypoxic cancer cells, so the administration of radiotherapy while breathing hyperbaric oxygen may result in a reduction in mortality and recurrence. To assess the benefits and harms of radiotherapy while breathing HBO. In March 2011 we searched The Cochrane Central Register of Controlled Trials (CENTRAL), (The Cochrane Library, Issue 3), MEDLINE, EMBASE, DORCTHIM and reference lists of articles. Randomised and quasi-randomised studies comparing the outcome of malignant tumours following radiation therapy while breathing HBO versus air. Three review authors independently evaluated the quality of the relevant trials and extracted the data from the included trials. Nineteen trials contributed to this review (2286 patients: 1103 allocated to HBOT and 1153 to control). With HBOT, there was a reduction in mortality for head and neck cancers at both one year and five years after therapy (risk ratio (RR) 0.83, P = 0.03, number needed to treat (NNT) = 11; and RR 0.82, P = 0.03, NNT = 5 respectively), as well as improved local tumour control at three months (RR with HBOT 0.58, P = 0.006, NNT = 7). The effect of HBOT varied with different fractionation schemes. Local tumour recurrence was less likely with HBOT at one year (head and neck: RR 0.66, P < 0.0001, NNT = 5), two years (uterine cervix: RR 0.60, P = 0.04, NNT = 5) and five years (head and neck: (RR 0.77, P = 0.01, NNT = 6). Any advantage is achieved at the cost of some adverse effects. There was a significant increase in the rate of both severe radiation tissue injury (RR 2.35, P < 0.0001, (number needed to harm (NNH) = 8) and the chance of seizures during therapy (RR 6.76, P = 0.03, NNH = 22) with HBOT. There is some evidence that HBOT improves local tumour control and mortality for cancers of the head and neck, and local tumour recurrence in cancers of the head and neck, and uterine cervix. These benefits may only occur with unusual fractionation schemes. HBOT is associated with significant adverse effects including oxygen toxic seizures and severe tissue radiation injury. The methodological and reporting inadequacies of the studies included demand a cautious interpretation. More research is needed for head and neck cancer, but is probably not justified for bladder cancer. There is little evidence available concerning malignancies at other anatomical sites on which to base a recommendation.
    Cochrane database of systematic reviews (Online) 01/2012; 4:CD005007. · 5.70 Impact Factor
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    ABSTRACT: Cancer is a significant global health problem. Radiotherapy is a treatment for many cancers and about 50% of patients having radiotherapy with be long-term survivors. Some will experience late radiation tissue injury (LRTI) developing months or years later. Hyperbaric oxygen therapy (HBOT) has been suggested as a treatment for LRTI based upon the ability to improve the blood supply to these tissues. It is postulated that HBOT may result in both healing of tissues and the prevention of problems following surgery. To assess the benefits and harms of HBOT for treating or preventing LRTI. In March 2011 we updated the searches of the Cochrane Central Register of Controlled Trials (CENTRAL), (The Cochrane Library, Issue 1), MEDLINE, EMBASE, DORCTIHM and reference lists of articles. Randomised controlled trials (RCTs) comparing the effect of HBOT versus no HBOT on LRTI prevention or healing. Three review authors independently evaluated the quality of the relevant trials using the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions and extracted the data from the included trials. Eleven trials contributed to this review (669 participants). For pooled analyses, investigation of heterogeneity suggested important variability between trials but there was some evidence that HBOT is more likely to achieve mucosal coverage with osteoradionecrosis (ORN) (risk ratio (RR) 1.3; 95% confidence interval (CI) 1.1 to 1.6, P = 0.003, number needed to treat for an additional beneficial outcome (NNTB) 5). From single studies there was a significantly increased chance of improvement or cure following HBOT for radiation proctitis (RR 1.72; 95% CI 1.0 to 2.9, P = 0.04, NNTB 5), and following both surgical flaps (RR 8.7; 95% CI 2.7 to 27.5, P = 0.0002, NNTB = 4) and hemimandibulectomy (RR 1.4; 95% CI 1.1 to 1.8, P = 0.001, NNTB 5). There was also a significantly improved probability of healing irradiated tooth sockets following dental extraction (RR 1.4; 95% CI 1.1 to 1.7, P = 0.009, NNTB 4).There was no evidence of benefit in clinical outcomes with established radiation injury to neural tissue, and no data reported on the use of HBOT to treat other manifestations of LRTI. These trials did not report adverse effects. These small trials suggest that for people with LRTI affecting tissues of the head, neck, anus and rectum, HBOT is associated with improved outcome. HBOT also appears to reduce the chance of ORN following tooth extraction in an irradiated field. There was no such evidence of any important clinical effect on neurological tissues. The application of HBOT to selected patients and tissues may be justified. Further research is required to establish the optimum patient selection and timing of any therapy. An economic evaluation should be undertaken.
    Cochrane database of systematic reviews (Online) 01/2012; 5:CD005005. · 5.70 Impact Factor
  • Internal Medicine Journal 05/2011; 41(5):437-8. · 1.82 Impact Factor
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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. · 2.83 Impact Factor
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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. · 6.20 Impact Factor
  • Yolanda Surjan, Helen Warren-Forward, Christopher Milross
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    ABSTRACT: Role expansion recognises enlargement of existing scope of practice within radiation therapy (RT). Over the past decade, there has been increasing involvement and movement towards advanced practice in the form of role extension in specialised areas of practice including brachytherapy, image fusion and quality assurance. It is also recognised that radiation therapy expert practitioners exist in the areas of imaging immobilisation, treatment, education and research. The acquisition of additional skills has hastened the need for autonomy within the RT profession and with this comes the responsibility to share our knowledge and specialist abilities with the wider community. Radiation therapy is a highly specialised profession working to treat a commonly encountered ailment like cancer and we should ask ourselves what other community members could benefit from our knowledge and skills.Cancer is not limited to the human population but affects animals as readily and severely. Particular types of cancers have been identified as being comparable with that of humans; one such tumour is squamous cell carcinoma (SCC). Squamous cell carcinoma is the most commonly found tumour of the eye and adnexa in horses. Comparatively, SCC in humans is the most common cancer in Australia. Whilst human treatment is well established with surgery and radiation therapy offering comparable control rates, the treatment within Australia’s Veterinary Oncology field is currently at a standstill. It is reported, however, that the use of interstitial brachytherapy has been shown to be highly effective and thoroughly practiced and established within the United States of America (USA). This paper reviews current literature in readiness for the potential for radiation therapy cross-over into the veterinary sphere with regard to the implementation of treatment and radiation safety protocols for the use of interstitial brachytherapy in horses.
    Radiography 01/2011; 17(3):250-253.
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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
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    ABSTRACT: This study examines the prognostic significance of human papillomavirus (HPV) in patients with locally advanced oropharyngeal squamous cell carcinoma (SCC) treated primarily with surgery or definitive radiotherapy. One hundred and ninety-eight patients with Stage 3/4 SCC were followed up for recurrence in any form or death from any cause for between 1 and 235 months after diagnosis. HPV status was determined using HPV E6-targeted multiplex real-time PCR/p16 immunohistochemistry. Determinants of recurrence and mortality hazards were modelled using Cox's regression with censoring at follow-up dates. Forty-two per cent of cancers were HPV-positive (87% type 16). HPV predicted loco-regional control, event-free survival and overall survival in multivariable analysis. Within the surgery with adjuvant radiotherapy (n=110), definitive radiotherapy-alone (n=24) and definitive radiotherapy with chemotherapy (n=47) groups, patients with HPV-positive cancers were one-third or less as likely to have loco-regional recurrence, an event or to die of any cause as those with HPV-negative cancers after adjusting for age, gender, tumour grade, AJCC stage and primary site. The 14 patients treated with surgery alone were considered too few for multivariable analysis. HPV status predicts better outcome in oropharyngeal cancer treated with surgery plus adjuvant radiotherapy as well as with definitive radiation therapy±chemotherapy.
    British Journal of Cancer 10/2010; 103(10):1510-7. · 5.08 Impact Factor
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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. · 2.83 Impact Factor
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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. · 2.83 Impact Factor
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    ABSTRACT: This study examines the prognostic significance of epidermal growth factor receptor (EGFR) expression in relation to human papillomavirus (HPV) status in oropharyngeal squamous cell carcinoma (SCC). Pathological diagnosis of 270 oropharyngeal SCCs was verified by the study pathologist; clinical details were extracted from institutional databases. Recurrence in any form or death from any cause was recorded for a median of 2.5 (range: 0-19.3) years after diagnosis. HPV status was determined by HPV E6-targeted multiplex real-time PCR/p16 immunohistochemistry; EGFR expression was evaluated by semiquantitative immunohistochemistry. Determinants of recurrence and mortality hazards were modelled using Cox regression with censoring at dates of last follow-up. Thirty-seven percent of cancers were HPV-positive (91% type 16). HPV was a predictor of loco-regional recurrence, event-free and overall survival after adjustment for clinicopathological variables and EGFR. Patients with EGFR-positive cancers were 5-fold more likely to have loco-regional failure relative to those with EGFR-negative cancers. Patients with HPV-negative/EGFR-positive cancers had an adjusted 13-fold increased risk of having a loco-regional failure, an almost 4-fold increased risk of having an event and more than a 4-fold increased risk of dying of any cause relative to those with HPV-positive/EGFR-negative cancers. There was weak evidence that the effects of EGFR on outcome were limited to patients with HPV-negative cancers. HPV and EGFR are independent prognostic markers in oropharyngeal SCC. Combining testing for HPV and EGFR appears to provide additional prognostic information.
    European journal of cancer (Oxford, England: 1990) 07/2010; 46(11):2088-96. · 4.12 Impact Factor
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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
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    ABSTRACT: Our previous studies of tonsillar cancers from New South Wales, Australia, and Jilin Province in the north-east of China, provided evidence that the proportion of these cancers attributable to human papillomavirus (HPV) varies geographically. This study provides the first data on HPV in tonsillar cancers from Hong Kong. A total of 49 Hong Kong tonsillar cancers were analysed for HPV DNA by PCR/sequencing and for p16(INK4A), retinoblastoma (pRb) protein, cyclin D1 and p53 expression by semiquantitative immunohistochemistry as evidence of virus causality. Results were compared with those from New South Wales and Jilin Province. Of the 31 Hong Kong cancers with amplifiable DNA, nine (29%) were HPV positive by PCR compared with 46% from New South Wales and 0% from Jilin Province. HPV positivity correlated with female gender, young age, over-expression of p16(INK4A) and loss of pRb and cyclin D1. Five-year disease-specific survival for patients with HPV positive and HPV negative cancers was 82 and 42%, respectively. Relationships between HPV status and cell protein expression in Hong Kong cancers were consistent with those from New South Wales and Jilin Province. The proportion of HPV-associated cancers reflected the relative incidence of oropharyngeal cancer in these regions. HPV is responsible for a small proportion of tonsillar cancers in Hong Kong patients. Differences in the proportions of tumours attributable to HPV in Hong Kong, New South Wales and Jilin Province may be due to environmental, cultural or genetic factors in the different populations.
    Pathology 05/2007; 39(2):217-22. · 2.66 Impact Factor

Publication Stats

181 Citations
56.41 Total Impact Points


  • 2007–2014
    • Royal Prince Alfred Hospital
      • Department of Radiation Oncology
      Camperdown, New South Wales, Australia
    • Sydney Head and Neck Cancer Institute
      Sydney, New South Wales, Australia
  • 2012
    • University of New South Wales
      • Prince of Wales Hospital
      Kensington, New South Wales, Australia