Medicine (St Vincent's) - Research Publications
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ItemA phase II trial of paclitaxel and epirubicin in advanced breast cancer(NATURE PUBLISHING GROUP, 2000-08)Initial trials of paclitaxel and doxorubicin in advanced breast cancer yielded high response rates but significant cardiac toxicity was observed. In this phase II trial we investigated the efficacy and safety of paclitaxel combined with epirubicin. Patients with advanced breast cancer, performance status 0-2, measurable disease, and a normal left ventricular ejection fraction, who may have received adjuvant chemotherapy were treated with epirubicin 75 mg m(-2) followed by a 3-h infusion of paclitaxel 175 mg m(-2) repeated every 3 weeks. Forty-three eligible patients were treated at six centres. 67% patients received the maximum of six cycles. The response rate was 54% (95% CI 38-69%), 12% CR and 42% PR. Estimated median progression-free survival was 6.9 months (95% CI 5.4-10.0) and estimated median overall survival was 17.9 months (95% CI 14.2-25.7). Four patients had a decrease in the left ventricular ejection fraction (LVEF) of > or =20% of baseline value, and in two patients the LVEF decreased to below the lower limit of normal, but no patient developed clinical evidence of cardiac failure. Grade 4 neutropenia occurred in 56% cycles, but only 4% of cycles were complicated by febrile neutropenia. Grade 3 or 4 non-haematologic toxicity was uncommon. In conclusion, paclitaxel 175 mg m(-2) and epirubicin 75 mg m(-2) is a well tolerated, promising regimen for the treatment of advanced breast cancer.
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ItemFDG-PET/CT imaging for evaluating durable responses to immune check point inhibitors in patients with advanced cutaneous squamous cell carcinoma(BMC, 2021-10-13)BACKGROUND: The role of FDG-PET/CT imaging in assessing response to immunotherapy in advanced cutaneous squamous cell carcinoma (CSCC) is unknown. This study compared complete metabolic response (CMR) rates by FDG-PET and RECIST1.1 via CT or MRI in patients on cemiplimab for > 10 months. METHODS: This was a single-centre retrospective study of 15 patients treated with cemiplimab for advanced CSCC who had CT/MRI and FDG-PET/CT at > 10 months to assess metabolic treatment response. The median age was 73 years (range 55-84) and 93% were male. RECIST1.1 and PERCIST1.0 tumor responses were evaluated by blinded readers. RESULTS: Seventy-three percent (11/15) (95%CI 44.9, 92.2%) achieved a CMR on PET. Of these 11, on RECIST1.1 there was one complete response, 9 partial responses and one stable disease. CONCLUSIONS: In patients on cemiplimab for > 10 months, there was discordance between CR rates on FDG-PET versus RECIST1.1. FDG-PET/CT may have utility for clarifying depth of response in patients treated with immunotherapy for CSCC.
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ItemBiology and Treatment Advances in Cutaneous Squamous Cell Carcinoma(MDPI, 2021-11)Cutaneous squamous cell carcinoma (CSCC) is the second most common skin cancer diagnosed worldwide. CSCC is generally localized and managed with local therapies such as excision and/or radiotherapy. For patients with unresectable or metastatic disease, recent improvements in our understanding of the underlying biology have led to significant advancements in treatment approaches-including the use of immune checkpoint inhibition (ICI)-which have resulted in substantial gains in response and survival compared to traditional cytotoxic approaches. However, there is a lack of understanding of the biology underpinning CSCC in immunocompromised patients, in whom the risk of developing CSCC is hundreds of times higher compared to immunocompetent patients. Furthermore, current ICI approaches are associated with significant risk of graft rejection in organ transplant recipients who make up a significant proportion of immunocompromised patients. Ongoing scientific and clinical research efforts are needed in order to maintain momentum to increase our understanding and refine our therapeutic approaches for patients with CSCC.
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ItemThe role of human papillomavirus in p16-positive oral cancers(WILEY, 2018-01)BACKGROUND: The aim of this study was to identify the presence and frequency of human papillomavirus (HPV) nucleic acid in p16-positive oral squamous cell carcinomas (OSCCs), to assess whether the virus was transcriptionally active and to assess the utility of p16 overexpression as a surrogate marker for HPV in OSCC. METHODS: Forty-six OSCC patients treated between 2007 and 2011 with available formalin-fixed paraffin-embedded (FFPE) specimens were included. Twenty-three patients were positive for p16 by immunohistochemistry (IHC) and these were matched with 23 patients with p16-negative tumours. Laser capture microdissection of the FFPE OSCC tissues was undertaken to isolate invasive tumour tissue. DNA was extracted and tested for high-risk HPV types using a PCR-ELISA method based on the L1 SPF10 consensus primers, and a real-time PCR method targeting HPV-16 and HPV-18 E6 region. Genotyping of HPV-positive cases was performed using a reverse line blot hybridization assay (Inno-LiPA). RNAScope® (a chromogenic RNA in situ hybridization assay) was utilized to detect E6/E7 mRNA of known high-risk HPV types for detection of transcriptionally active virus. RESULTS: HPV DNA was found in 3 OSCC cases, all of which were p16 IHC-positive. Two cases were genotyped as HPV-16 and one as HPV-33. Only one of the HPV-16 cases was confirmed to harbour transcriptionally active virus via HPV RNA ISH. CONCLUSION: We have shown that the presence of transcriptionally active HPV rarely occurs in OSCC and that p16 is not an appropriate surrogate marker for HPV in OSCC cases. We propose that non-viral mechanisms are responsible for the majority of IHC p16 overexpression in OSCC.
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ItemTimely initiation of chemotherapy: a systematic literature review of six priority cancers - results and recommendations for clinical practice(WILEY, 2017-01)This review evaluated the association between time-to-chemotherapy (TTC) and survival in six priority cancers. A systematic review of the literature was undertaken for papers indexed in the MEDLINE and Cochrane Library databases from the earliest index until April 2014. The methodology used has been published in a separate paper (Guidelines for timely initiation of chemotherapy: a proposed framework for access to medical oncology and haematology cancer clinics and chemotherapy services). The optimal timing of chemotherapy in breast cancer is unclear as available studies are of low quality, report inconsistent results and are limited to the adjuvant setting. However, increased TTC may have a negative prognostic impact, and delays beyond 4 weeks should be avoided. Studies suggest that the optimal timing for initiation of adjuvant chemotherapy for surgically resected colorectal cancer is 4-8 weeks post-surgery. Timing of chemotherapy for metastatic colorectal cancer does not influence survival. There is a paucity of studies to guide the timing of chemotherapy for the treatment of lymphoma and myeloma; no definitive conclusions can be drawn, and clinician discretion should be applied. The optimal timing of chemotherapy in lung cancer is unclear; however, rapid tumour growth and poor disease prognosis suggest that delays should be avoided wherever possible. The optimal timing of chemotherapy in ovarian cancer is unclear as available studies are of low level, report inconsistent results and are limited to the post-surgery setting; however, increased TTC may have a negative prognostic impact; therefore, delays beyond 4 weeks should be avoided.
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ItemIndividualised mindfulness-based stress reduction for head and neck cancer patients undergoing radiotherapy of curative intent: a descriptive pilot study(WILEY, 2017-03)People with head and neck cancer (HNC) experience elevated symptom toxicity and co-morbidity as a result of treatment, which is associated with poorer psychosocial and quality-of-life (QoL) outcomes. This Phase I study examined whether an individualised mindfulness-based stress reduction (IMBSR) programme could be successfully used with HNC patients undergoing curative treatment. Primary aims were to explore feasibility, compliance, acceptability and fidelity. Secondary aims were to determine whether (1) participation in the intervention was associated with changes in post-intervention mindfulness and (2) post-intervention mindfulness was associated with post-intervention distress and QoL. Nineteen HNC patients participated in a seven-session IMBSR programme with pre- and post-test outcome measures of psychological distress, depression, anxiety and QoL. Primary aims were assessed by therapists or participants. Mindfulness, distress and QoL were assessed using self-report questionnaires at pre- and post-intervention. Longer time spent meditating daily was associated with higher post-intervention mindfulness. After controlling for pre-intervention mindfulness, there was an association between higher post-intervention mindfulness and lower psychological distress and higher total, social and emotional QoL. This study offers important preliminary evidence than an IMBSR intervention can be administered to HNC patients during active cancer treatment. A randomised controlled trial is warranted to confirm these findings.
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Itemp16-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(WILEY-BLACKWELL, 2016-04-15)BACKGROUND: The incidence of p16 overexpression and the role of human papillomavirus (HPV) in cutaneous head and neck squamous cell carcinoma (cHNSCC) are unclear. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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ItemHealth-Related Quality of Life (HRQL) in Patients with Advanced Cutaneous Squamous Cell Carcinoma (CSCC) Treated with Cemiplimab: Post Hoc Exploratory Analysis of a Phase 2 Clinical Trial(National Society for Cutaneous Medicine, 2020-10-27)Abstract not available.
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ItemPhase 2 Study of Cemiplimab in Patients with Advanced Cutaneous Squamous Cell Carcinoma (CSCC): Longer Follow-Up(National Society for Cutaneous Medicine, 2020-10-27)Abstract not available.
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ItemCemiplimab Improves Health-Related Quality of Life (HRQoL) and Reduces Pain in Patients with Advanced Cutaneous Squamous Cell Carcinoma (CSCC): Results from a Post Hoc Exploratory Analysis of a Phase 2 Clinical Trial(National Society for Cutaneous Medicine, 2021-01-01)Abstract not available.