ORCID Profile
0000-0002-6639-0035
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Liverpool Hospital
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Publisher: Wiley
Date: 06-2009
DOI: 10.1118/1.3181637
Publisher: Elsevier BV
Date: 04-2016
Publisher: Elsevier BV
Date: 05-2010
DOI: 10.1016/J.CLON.2010.02.002
Abstract: To identify practical intensity-modulated radiotherapy planning solutions when attempting dose escalation in the skull base. Twenty cases of skull base meningioma were re-planned using a variation of beam number (three, five, seven and nine), beam arrangement (coplanar vs non-coplanar) and multileaf collimator (MLC) width (2.5 mm vs 10 mm) to 60 Gy/30 fractions. Plan quality and planning target volume coverage was assessed using planning target volume V(95%), equivalent uniform dose (EUD) and integral dose. Critical structures were maintained below clinical tolerance levels. The 2.5 mm MLC achieved an average improvement in V(95%) by 22.8% (P=0.0003), EUD by 3.7 Gy (P=0.002) and reduced the integral dose by 13.4 Gy (P=0.0001). V(95%) and the integral dose improved with five vs three beams and seven vs five beams, but did not change with nine vs seven beams. There was no effect of beam number on EUD. There was no difference in V(95%) (P=0.54), integral dose (P=0.44) or EUD (P=0.47) for beam arrangement used. Segments per plan increased by a factor of 1.5 with each addition of two beams to a plan, and by a factor of 2.5 for 2.5 mm MLC plans vs 10 mm MLC plans. We present evidence-based planning solutions for skull base intensity-modulated radiotherapy, and show that 2.5 mm MLC and five to seven beams can achieve safe dose escalation up to 60 Gy. This must be balanced with an increase in segmentation, which will increase treatment times.
Publisher: American Society of Clinical Oncology (ASCO)
Date: 05-2015
DOI: 10.14694/EDBOOK_AM.2015.35.E519
Abstract: Merkel cell carcinoma (MCC) is an aggressive neuroendocrine cutaneous cancer that predominantly occurs in patients who are older, and is associated with a high rate of distant failure and mortality. Current management strategies that incorporate surgery and radiotherapy achieve high rates of locoregional control, but distant failure rates remain problematic, highlighting the need for new effective systemic therapies. Chemotherapy can achieve high response rates of limited duration in the metastatic setting, but its role in definitive management remains unproven. Recent developments in our knowledge about the biology of MCC have led to the identification of new potential therapeutic targets and treatments. A key finding has been the discovery that a human polyomavirus may be a causative agent. However, emerging data suggests that MCC may actually be two distinct entities, viral-associated and viral-negative MCC, which is likely to have implications for the management of MCC in the future and for the development of new treatments. In this review, we discuss recent discoveries about the biology of MCC, current approaches to management, and new therapeutic strategies that are being investigated.
Publisher: Elsevier BV
Date: 07-2018
Abstract: As early detection of recurrent melanoma maximizes treatment options, patients usually undergo post-operative imaging surveillance, increasingly with FDG-PET/CT (PET). To assess this, we evaluated stage 3 melanoma patients who underwent prospectively applied and sub-stage-specific schedules of PET surveillance. From 2009, patients with stage 3 melanoma routinely underwent PET +/- MRI brain scans via defined schedules based on sub-stage-specific relapse probabilities. Data were collected regarding patient characteristics and outcomes. Contingency analyses were carried out of imaging outcomes. One hundred and seventy patients (stage 3A: 34 3B: 93 3C: 43) underwent radiological surveillance. Relapses were identified in 65 (38%) patients, of which 45 (69%) were asymptomatic. False-positive imaging findings occurred in 7%, and 6% had treatable second (non-melanoma) malignancies. Positive predictive values (PPV) of in idual scans were 56%-83%. Negative scans had predictive values of 89%-96% for true non-recurrence [negative predictive values (NPV)] until the next scan. A negative PET at 18 months had NPVs of 80%-84% for true non-recurrence at any time in the 47-month (median) follow-up period. Sensitivity and specificity of the overall approach of sub-stage-specific PET surveillance were 70% and 87%, respectively. Of relapsed patients, 33 (52%) underwent potentially curative resection and 10 (16%) remained disease-free after 24 months (median). Application of sub-stage-specific PET in stage 3 melanoma enables asymptomatic detection of most recurrences, has high NPVs that may provide patient reassurance, and is associated with a high rate of detection of resectable and potentially curable disease at relapse.
Publisher: Elsevier BV
Date: 12-2009
DOI: 10.1016/J.CLON.2009.08.013
Abstract: Radiotherapy is an important treatment modality for meningioma. We aimed to review the clinical outcomes for meningioma patients treated with radiotherapy in the Addenbrooke's Hospital Oncology Department. A retrospective chart review was carried out on patients with meningioma referred and treated in the department between 1 November 1996 and 31 October 2006. Patient details and outcomes were recorded and the results were analysed to assess survival outcomes. Survival data were confirmed by the Eastern Cancer Registration and Information Centre. In total, 174 patients were referred to the department for an oncology opinion. Of these, 128 proceeded to radiotherapy. The median follow-up was 5.3 years (range 2.1-11.9 years). Sixty-seven per cent of the patients were older than 50 years, and the female: male ratio was 2.2: 1. Overall survival was 78% at the time of follow-up, with death related to meningioma in 7% of the total cohort. Local control was 85% overall, 93% for grade 1 disease, 45% for grade 2 disease and 82% for grade 3 disease. Patients with non-benign disease were more likely to receive >50Gy (27% of grade 1 lesions vs 65% of grade 2/3 lesions), but despite this local control remained poor, even with the higher dose delivered (local control 60 and 40% for grade 2 lesions treated with 50 and >50Gy, respectively, and 100 and 75% for grade 3 lesions treated with 50 and >50Gy, respectively). Our cohort of patients had an overall local control and survival similar to those documented from other departments. Grade was an important prognostic factor. Patients treated with >50Gy had worse local control outcomes, probably due to selection bias. Dose escalation may still be appropriate for high-risk disease, and may be more effective with more conformal techniques, such as intensity-modulated radiotherapy.
Publisher: Elsevier BV
Date: 04-2010
DOI: 10.1016/J.CLON.2010.01.004
Abstract: Therapeutic radiotherapy to lesions of the skull base is limited by complex target shapes and their proximity to organs at risk. Intensity-modulated radiotherapy (IMRT) using helical tomotherapy may result in improved dose distributions and safer dose escalation. The aim of this study was to compare plan efficacy and efficiency using, linac-based micro-multileaf collimator (mMLC) IMRT and helical tomotherapy. Five cases of skull base meningioma, previously treated with three-dimensional conformal radiotherapy (50 Gy/30 fractions) were identified. They were re-planned to a dose of 60 Gy/30 fractions using IMRT with Moduleaf mMLC (2.5 mm) and helical tomotherapy. Plan efficacy was compared using measures of PTV(60) coverage (D(min), D(max), V(90%), V(95%) and V(100%)). Plan efficiency was assessed by comparing estimated beam-on times. The critical structure dose was limited to below predetermined tolerance levels in all cases, with similar doses obtained between techniques. The average PTV(60)D(max), D(min), D(med), D(mean), V(90%), V(95%) and V(100%) across the five cases achieved were as follows: mMLC IMRT: 64.9 Gy, 40.1 Gy, 60 Gy, 59.6 Gy, 95.4%, 88.8% and 69.2%, respectively helical tomotherapy: 67.2 Gy, 50.3 Gy, 60 Gy, 59.9 Gy, 95.8%, 83.5% and 51.9%, respectively. The average treatment time per fraction was 18.4 min for IMRT with mMLC and 6.7 min for helical tomotherapy. This study shows that safe dose escalation to a dose of 60G y to skull base lesions can be achieved using either mMLC- or helical tomotherapy-based IMRT. A plan comparison between the two solutions is difficult, but they seem to be similar in efficacy with any small differences being difficult to interpret and of questionable clinical significance. Helical tomotherapy has the advantage of a significantly decreased beam-on time.
Publisher: Elsevier BV
Date: 04-2018
Publisher: Wiley
Date: 21-06-2016
Abstract: Cutaneous squamous cell carcinoma of the head and neck (cHNSCC) metastatic to the parotid has a moderate risk of recurrence despite multimodality treatment. Immunosuppression is associated with lower rates of long-term cure. Our aim was to review outcomes of current management in a tertiary centre with a view to targeting future strategies. A retrospective review of clinico-pathological data and outcomes for patients with metastatic cHNSCC involving the parotid gland, undergoing radical surgery and adjuvant radiotherapy during 2000-2014 was conducted. The Kaplan-Meier method was used to determine time-to-event outcomes. One hundred and thirty-two patients met the inclusion criteria. Median follow-up was 5.0 years. Five-year overall (OS), cancer-specific (CSS) and progression free survival (PFS) were 44% (95% Confidence Interval (CI) 34-53%), 64% (95% CI 52-74%) and 37% (95% CI 28-47%) respectively. Locoregional control (LRC) was 68% (95% CI 55-77%) at 5 years. Immunosuppressed patients fared worse (compared with immune-competent) with five-year OS, CSS, and PFS of 14% versus 53% (HR = 3.19 95% CI 1.91-5.34), 40% versus 71% (Hazard Ratio (HR) = 2.92 95% CI 1.38-6.19) and 10% versus 46% (HR = 2.51 95% CI 1.52-4.14) respectively. On multivariate analysis, immune status strongly predicted OS (P < 0.001), CSS (P = 0.003), DMFS (P < 0.001) and PFS (P < 0.001), but not LRC. Largest lymph node size was the only significant factor predictive for LRC on multivariate analysis (P = 0.02). Despite multimodality treatment metastatic cHNSCC involving the parotid shows moderate rates of recurrence. Immunosuppressed patients with this disease have a particularly poor prognosis, demonstrating lower rates of CSS with similar rates of LRC compared to their immunocompetent counterparts.
Publisher: Wiley
Date: 10-06-2017
DOI: 10.1111/AJD.12520
Abstract: Squamous cell carcinoma of the scalp is a common clinical problem in an aging population. Despite its high incidence, little has been documented regarding treatment or outcomes. We retrospectively analysed 235 cases treated with curative intent at Peter MaCallum Cancer Centre between 1998 and 2010. The cohort was analysed for its characteristics, management, survival and prognostic factors. The patients were primarily male (88%) with a median age of 79 years (range 53-98 years). There was a high proportion of immunosuppressed patients (29%) and stage T2 (48%) tumours. Management included surgery (45%), radiotherapy (28%) and surgery and adjuvant radiotherapy (26%). Median follow up from treatment was 4.5 years. Estimated 5-year overall survival (OS), disease-specific survival and progression-free survival (PFS) were 59, 94 and 51%, respectively. The 5-year cumulative incidence of local and regional relapse was 11 and 7%, respectively. There were four patients who developed distant metastases and died of their disease. Statistically significant prognostic factors identified for poor outcomes for OS and PFS were T2 stage (hazard ratio [1.7 and 2.1) and immunosuppression (HR 3.3 and 3.4). We conclude the presence of immunosuppression and T2 stage is prognostic for survival. Further research to establish treatment principles is warranted.
Publisher: Elsevier BV
Date: 06-2007
Publisher: Oxford University Press (OUP)
Date: 27-10-2016
DOI: 10.1093/NAR/GKW995
Publisher: Wiley
Date: 06-2008
DOI: 10.1118/1.2961544
Publisher: Wiley
Date: 05-02-2018
Abstract: TROG 09.03 prospectively studied the utility of Fluorine-18 Fluorodeoxyglucose (18-FDG) PET in the management of Merkel cell carcinoma of skin. Following consent and registration, a pre-treatment FDG-PET/CT was performed. Sites of avid disease were confirmed by cytology where practicable. Following surgery, patients with AJCCv7 Stages IIA-IIIB disease were treated with chemo-radiotherapy and reassessed with a post-treatment PET. Fifty-eight subjects (45 males and 13 females, median age 68 years) were enrolled between 2011 and 2015, 43 patients of whom went on to receive chemo-radiotherapy. An occult primary was present in 22 (37.9%), T1 in 22 (37.9%) and T2 disease in 14 (24.1%). Nodal disease was present in 69% of cases. Fifty per cent of subjects had gross residual disease at the primary site and/or nodal site at the time of registration. 18-FDG PET/CT had a sensitivity of 94.74% (95% CI 82-99.3%) and a specificity of 88.24% (95% CI 63.56-98.54). The positive predictive value was 94.74% (83.01-98.51) and the negative predictive value was 88.24% (95% CI 65.81-96.69). The pre-treatment PET influenced a treatment decision in 27.6% of cases. Upstaging occurred in 15 (25.9%), with no down staging. Other diseases were identified in 4 (6.9%) patients. Univariate analysis failed to demonstrate that pre-treatment SUV levels or a negative post-treatment PET had any impact on overall survival. PET staged patients had 89% 3-year in-field loco-regional control and 76% 3-year overall survival. Staging 18-FDG-PET significantly influenced treatment decisions in approximately one-third of cases of MCC and should be considered in the routine pre-treatment work-up. Post-treatment PET was not found to be prognostic. Funding through the Medicare Benefits Schedule needs to be considered for high risk MCC.
Publisher: Wiley
Date: 22-03-2017
DOI: 10.1111/CGE.12994
Abstract: Many families with a high burden of colorectal cancer fulfil the clinical criteria for Lynch Syndrome. However, in about half of these families, no germline mutation in the mismatch repair genes known to be associated with this disease can be identified. The aim of this study was to find the genetic cause for the increased colorectal cancer risk in these unsolved cases. To reach the aim, we designed a gene panel targeting 112 previously known or candidate colorectal cancer susceptibility genes to screen 274 patient s les for mutations. Mutations were validated by Sanger sequencing and, where possible, segregation analysis was performed. We identified 73 interesting variants, of whom 17 were pathogenic and 19 were variants of unknown clinical significance in well-established cancer susceptibility genes. In addition, 37 potentially pathogenic variants in candidate colorectal cancer susceptibility genes were detected. In conclusion, we found a promising DNA variant in more than 25 % of the patients, which shows that gene panel testing is a more effective method to identify germline variants in CRC patients compared to a single gene approach.
Publisher: Elsevier BV
Date: 09-2021
Publisher: Wiley
Date: 16-02-2016
DOI: 10.1002/CNCR.29901
Abstract: The incidence of p16 overexpression and the role of human papillomavirus (HPV) in cutaneous head and neck squamous cell carcinoma (cHNSCC) are unclear. One hundred forty-three patients with cHNSCC lymph node metastases involving the parotid gland were evaluated for p16 expression by immunohistochemistry. The detection of 18 high-risk HPV subtypes was performed with HPV RNA in situ hybridization for a subset of 59 patients. The results were correlated with clinicopathological features and outcomes. The median follow-up time was 5.3 years. No differences were observed in clinicopathological factors with respect to the p16 status. p16 was positive, weak, and negative in 45 (31%), 21 (15%), and 77 cases (54%), respectively. No high-risk HPV subtypes were identified, regardless of the p16 status. The p16 status was not prognostic for overall (hazard ratio, 1.08 95% confidence interval [CI], 0.85-1.36 P = .528), cancer-specific (hazard ratio, 1.12 95% CI, 0.77-1.64 P = .542), or progression-free survival (hazard ratio, 1.03 95% CI, 0.83-1.29 P = .783). Distant metastasis-free survival, freedom from locoregional failure, and freedom from local failure were also not significantly associated with the p16 status. p16 positivity is common but not prognostic in cHNSCC lymph node metastases. High-risk HPV subtypes are not associated with p16 positivity and do not appear to play a role in this disease. HPV testing, in addition to the p16 status in the unknown primary setting, may provide additional information for determining a putative primary site.
Publisher: Wiley
Date: 06-2008
DOI: 10.1118/1.2961819
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2016
DOI: 10.1097/DSS.0000000000000864
Abstract: In-transit metastasis from cutaneous squamous cell carcinoma (SCC) is an uncommon form of metastasis through lymphatics and occurs more commonly in immunosuppressed patients. To identify cases of in-transit SCC and determine patient characteristics, tumor features, management, and prognosis. A multicenter case series treated by Australian and New Zealand clinicians. In 31 patients, median age was 72 years (range 52–99) and 68% were immunocompetent. Tumors occurred on the head and neck in 94% of cases, with 71% of all tumors occurring on the scalp, forehead, or temple. The median time to presentation with in-transit SCC from treatment of the initial tumor was 5 months. Management included surgery (94%), radiotherapy (77%), chemotherapy (10%), and reduction of immunosuppression (3%). Median follow-up was 12 months. Overall survival at 3 and 5 years were 27% and 13%, respectively. In-transit metastases are described in 31 patients, of whom the majority was immunocompetent. The scalp, forehead, and temple were the most common sites. New clinical and histological diagnostic criteria are proposed. Prognosis was poor with 5-year survival of 13%. Recommended management is a combination of surgery and adjuvant radiotherapy. Reduction of any iatrogenic immunosuppression should be considered.
Publisher: Wiley
Date: 18-01-2018
DOI: 10.1111/AJD.12779
Abstract: To describe the characteristics, subsequent management and outcomes of patients referred for further management following Mohs micrographic surgery (MMS) for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Retrospective analysis of patients referred to a quaternary cancer centre from 2000 to 2015. In total, 83 lesions in 82 patients were referred for further management 52 (62%) were SCC and 80 (96%) were located in the head and neck. Reasons for referral included high-risk disease for consideration for adjuvant radiotherapy (37/83, 45%), inadequate resection (28/83, 34%) or recurrence following previous MMS (15/83, 17%). Fewer than 40% of the 69 referrals received from MMS surgeons included photos or an operative report and diagram. There was discordance in pathology opinion in 11 (13%) of cases. Histopathology from MMS was reviewed in eight cases and there was discordance with the in-hospital pathology opinion in six of these. In-hospital re-excision was performed in 19 cases and in five of these the pathology report on the paraffin-sectioned re-excised tissue was discordant with prior MMS assessment. Significantly, two cases were associated with a misinterpretation of lymphocytic infiltrate as residual disease in patients with chronic lymphocytic leukaemia (CLL). This study highlights some of the challenges and limitations of MMS. Early referral for multidisciplinary management is recommended when MMS resection margins are inadequate or uncertain, especially for high-risk SCC. We recommend that referrals be accompanied by histological material, as well as a detailed report with operative photos and diagrams. CLL can pose an intraoperative diagnostic challenge. Discrepancies in the interpretation of MMS slides present an opportunity for improvement, and our findings support the role of ongoing quality assurance programs.
Publisher: Frontiers Media SA
Date: 24-08-2021
Abstract: To examine the long-term survival outcome of dabrafenib in combination with trametinib in Chinese patients with unresectable or metastatic acral/cutaneous melanoma with BRAF-V600 mutation and to explore potential predictors of effectiveness. This was a long-term follow-up of Chinese patients with unresectable or metastatic BRAF V600-mutant acral/cutaneous melanoma administered dabrafenib (150 mg twice daily) plus trametinib (2 mg once daily) in an open-label, multicenter, single-arm, phase IIa study (NCT02083354). Efficacy endpoints included objective response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS). The impacts of baseline characteristics on PFS and OS were analyzed. A total of sixty patients were included. The median age was 48 years, and 24 patients (40.0%) were male. Totally 12 in iduals (20.0%) had acral melanoma, and 45 (75.0%) had failed previous systemic therapy. Up to July 2020, the median duration of follow-up was 37.0 (95% confidence interval [CI] 29.1-44.9) months. The updated ORR was 71.7% (95%CI 60.3%-83.1%). The 3-year OS rate was 28.8% (95%CI 19.1-43.6%) in the overall population, and 35.7% (95%CI 15.5–82.4%) in acral melanoma patients. The median DOR was 7.5 months (95%CI 4.5 to 10.5). Baseline normal lactic dehydrogenase (LDH), metastatic organ sites& and complete response to combination therapy with dabrafenib plus trametinib were associated with improved PFS and OS. Dabrafenib combined with trametinib confer long-term survival in Chinese patients with BRAF V600-mutant, unresectable or metastatic acral/cutaneous melanoma. t2/show/NCT02083354 , identifier NCT02083354.
Publisher: Elsevier BV
Date: 07-2005
Publisher: Public Library of Science (PLoS)
Date: 07-07-2020
Publisher: Elsevier BV
Date: 12-2019
No related grants have been discovered for Vanessa Estall.