Publications by authors named "Martin Haskett"

6 Publications

  • Page 1 of 1

A Distinct Pretreatment Immune Gene Signature in Lentigo Maligna Is Associated with Imiquimod Response.

J Invest Dermatol 2020 04 30;140(4):869-877.e16. Epub 2019 Sep 30.

Victorian Melanoma Service, Alfred Hospital, Melbourne, Victoria, Australia; School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.

Lentigo maligna (LM) is a common subtype of in situ melanoma on chronically sun-exposed skin, particularly the head and neck of older patients. Although surgery is the standard treatment, there is associated morbidity, and options such as imiquimod cream or radiotherapy may be used if surgery is refused or inappropriate. Complete response rates following imiquimod treatment are variable in the literature. The aim of this study was to evaluate the host immune response both before and following treatment with imiquimod to better identify likely responders. Paired pre- and post-imiquimod treatment specimens were available for 27 patients. Patients were treated with imiquimod 5 days per week for 12 weeks; at 16 weeks, lesions were excised for histological assessment. Of the 27 patients, 16 were responders and 11 failed to clear the disease. PDL1 protein expression was increased, accompanied by a unique gene signature in lesions from patients that subsequently histologically cleared LM by 16 weeks. This comprised 57 upregulated immune genes in signaling networks for antigen presentation, type I interferon signaling, and T-cell activation. This may represent an early responder group to imiquimod, and this unique gene signature potentially can be used as a biomarker of LM response to imiquimod.
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http://dx.doi.org/10.1016/j.jid.2019.07.725DOI Listing
April 2020

Implementing novel models of posttreatment care for cancer survivors: Enablers, challenges and recommendations.

Asia Pac J Clin Oncol 2015 Dec 6;11(4):319-27. Epub 2015 Aug 6.

Cancer Strategy and Development, Department of Health and Human Services, State Government of Victoria, Melbourne, Australia.

Aim: The American Society of Clinical Oncology and US Institute of Medicine emphasize the need to trial novel models of posttreatment care, and disseminate findings. In 2011, the Victorian State Government (Australia) established the Victorian Cancer Survivorship Program (VCSP), funding six 2-year demonstration projects, targeting end of initial cancer treatment. Projects considered various models, enrolling people of differing cancer types, age and residential areas. We sought to determine common enablers of success, as well as challenges/barriers.

Methods: Throughout the duration of the projects, a formal "community of practice" met regularly to share experiences. Projects provided regular formal progress reports. An analysis framework was developed to synthesize key themes and identify critical enablers and challenges. Two external reviewers examined final project reports. Discussion with project teams clarified content.

Results: Survivors reported interventions to be acceptable, appropriate and effective. Strong clinical leadership was identified as a critical success factor. Workforce education was recognized as important. Partnerships with consumers, primary care and community organizations; risk stratified pathways with rapid re-access to specialist care; and early preparation for survivorship, self-management and shared care models supported positive project outcomes. Tailoring care to individual needs and predicted risks was supported. Challenges included: lack of valid assessment and prediction tools; limited evidence to support novel care models; workforce redesign; and effective engagement with community-based care and issues around survivorship terminology.

Conclusion: The VCSP project outcomes have added to growing evidence around posttreatment care. Future projects should consider the identified enablers and challenges when designing and implementing survivorship care.
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http://dx.doi.org/10.1111/ajco.12406DOI Listing
December 2015

Characteristics and associations of high-mitotic-rate melanoma.

JAMA Dermatol 2014 Oct;150(10):1048-55

Victorian Melanoma Service, Alfred Hospital, Victoria, Australia.

Importance: Mitotic rate is now recognized as having independent prognostic significance in melanoma survival. However, its clinicopathologic associations have not been the focus of any previous study.

Objective: To identify a set of patient and tumor characteristics associated with high-mitotic-rate melanoma with the aim of facilitating the earlier detection of aggressive primary invasive melanoma.

Design, Setting, And Participants: Cross-sectional study of patients from a multidisciplinary melanoma clinic based in a public hospital. A total of 2397 cases from January 2006 to December 2011 were reviewed by the Victorian Melanoma Service, and 1441 patients with 1500 primary invasive melanomas were included in the study.

Main Outcomes And Measures: Mitotic rate was measured as number of mitoses per mm2 and analyzed as ordered categories (0, <1, 1 and <2, 2, 3-4, 5-9, and ≥10) according to patient demographics, phenotypic markers, historical data, tumor presentation, and histopathologic features.

Results: Melanomas with higher mitotic rates were more likely to occur in men (odds ratio [OR], 1.5; 95% CI, 1.3-1.8), patients 70 years or older (OR, 2.1; 95% CI, 1.7-2.8), and those with a history of solar keratosis (OR, 1.3; 95% CI, 1.1-1.6). These melanomas occurred more frequently on the head and neck (OR, 1.4; 95% CI, 1.0-1.9) and presented more often as amelanotic (OR, 1.9; 95% CI, 1.4-2.5) and rapidly growing (≥2 mm/mo) lesions (OR, 12.5; 95% CI, 8.4-18.5). An association was seen with the nodular melanoma subtype (vs superficial spreading [reference]) (OR, 2.5; 95% CI, 1.8-3.4), greater tumor thickness (vs ≤1 mm [reference]) (>1-4 mm: OR, 4.5; 95% CI, 3.2-6.1; >4 mm: OR, 12.6; 95% CI, 7.5-21.1), and ulceration (OR, 2.0; 95% CI, 1.5-2.7). These histopathologic features, along with amelanosis and rate of growth, remained as significant associations with high mitotic rate in the overall multivariate analysis.

Conclusions And Relevance: High-mitotic-rate primary cutaneous melanoma is associated with aggressive histologic features and atypical clinical presentation. It has a predilection for the head and neck region and is more likely to be seen in elderly men with a history of cumulative solar damage who present clinically with rapidly developing disease.
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http://dx.doi.org/10.1001/jamadermatol.2014.635DOI Listing
October 2014

Efficacy of imiquimod cream, 5%, for lentigo maligna after complete excision: a study of 43 patients.

Arch Dermatol 2011 Oct;147(10):1191-5

Victorian Melanoma Service, Level 1, Alfred Center, Alfred Health, Commercial Road, Melbourne, Victoria, Australia.

Objective: To determine the efficacy of imiquimod cream, 5%, in the treatment of lentigo maligna (LM).

Design: Open-label before-and-after interventional study.

Setting: A multidisciplinary melanoma clinic at a major tertiary hospital.

Patients: Forty-three patients with biopsy-proven LM of greater than 5 mm in diameter completed this study.

Interventions: Imiquimod cream, 5%, was applied to the lesion 5 days a week for 12 weeks. The original lesion was excised with a 5-mm margin.

Main Outcome Measures: The primary outcome was histopathologic evidence of LM in the excision specimen assessed independently by 2 of 3 dermatopathologists. Visible inflammation during treatment and macroscopic clearance were recorded.

Results: When 5 of the 43 patients with discordant histopathologic assessment of the excision specimen were excluded, 20 of 38 patients (53% [95% confidence interval, 36%-69%]) demonstrated histopathologic clearance of LM after imiquimod treatment. Visible inflammation was significantly associated with histopathologic clearance (P = .04), but the positive predictive value was low (62%). Macroscopic clearance showed some association with histopathologic clearance (P = .11). Dermatopathologist concordance for all 43 specimens was substantial (κ = 0.77; 95% confidence interval, 0.57-0.96).

Conclusions: Imiquimod cream, 5%, has limited efficacy in the treatment of LM when determined by histopathologic assessment of the entire treated area. The clinical signs of visible inflammation during treatment and apparent lesion clearance cannot be relied on to assess efficacy.
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http://dx.doi.org/10.1001/archdermatol.2011.260DOI Listing
October 2011

Dermoscopic features of extraocular sebaceous carcinoma.

Australas J Dermatol 2011 Aug 13;52(3):212-3. Epub 2010 Oct 13.

Churchill Hospital, Department of Dermatology, Oxford Radcliffe Health, Oxfordshire, UK.

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http://dx.doi.org/10.1111/j.1440-0960.2010.00699.xDOI Listing
August 2011

Dermatoscopy aids in the diagnosis of the solitary red scaly patch or plaque-features distinguishing superficial basal cell carcinoma, intraepidermal carcinoma, and psoriasis.

J Am Acad Dermatol 2008 Aug 11;59(2):268-74. Epub 2008 Jun 11.

Victorian Melanoma Service, The Alfred, Victoria, Australia.

Background: Intraepidermal carcinoma (IEC), superficial basal cell carcinoma (sBCC), and psoriasis are common entities that may all present as well-defined, brightly erythematous plaques. Currently, there are limited data on the dermatoscopic features that differentiate these diagnoses.

Objective: We sought to describe the most significant morphologic findings seen on dermatoscopy of IEC, sBCC, and psoriasis, and formulate a diagnostic model based on these features.

Method: We conducted a retrospective observational study using macrophotography and dermatoscopy to evaluate the presence or absence of dermatoscopic features and formulated diagnostic models for each diagnosis. A convenient sample of 300 lesions was collected from 255 patients from two hospital dermatology clinics and 4 private dermatology practices. These comprised 150 cases of sBCC, 100 cases of psoriasis, and 50 cases of IEC.

Results: The most significant dermatoscopic features of IEC were a clustered vascular pattern, glomerular vessels, and hyperkeratosis. When all 3 features were observed together, the diagnostic probability for IEC was 98%. sBCCs were characterized by a scattered vascular pattern, arborizing microvessels, telangiectatic or atypical vessels, milky-pink background, and brown dots/globules; the diagnostic probability was 99% if 4 of these 6 features were identified. For psoriasis, the significant features identified were a homogenous vascular pattern, red dots, and light-red background, yielding a diagnostic probability of 99% if all 3 features were present.

Limitations: Lack of evaluation of interobserver/intraobserver reproducibility is a limitation.

Conclusion: Dermatoscopy is valuable in the diagnosis and differentiation of IEC, sBCC, and psoriasis because of consistent dermatoscopic morphology.
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http://dx.doi.org/10.1016/j.jaad.2008.05.013DOI Listing
August 2008