Medicine (St Vincent's) - Research Publications
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ItemA clinical trial with protracted infusion 5-fluorouracil and mitomycin C for localized squamous cell carcinoma of the anus(WILEY, 2019-02)PURPOSE: Mitomycin C (MMC) plus standard 5-fluorouracil (FU) infusion in weeks 1 and 5 often contributes to radiotherapy interruptions and possibly less-than-ideal outcomes in anal cancer. This study was to evaluate alternative strategies for chemotherapy delivery that might be less toxic or more efficacious, and outcomes of patient-initiated treatment interruption for severe acute toxicity. MATERIALS AND METHODS: This was a prospective, nonrandomized study for patients with T1-4N0-3M0 anal squamous carcinoma. Radiotherapy of 54 Gy in 30 fractions over 6 weeks was given with infusion FU 300 mg/m2 /day for 96 hours/week for 6 weeks plus bolus MMC at 10 mg/m2 on D1. RESULTS: Fifty patients were recruited (72% female). Median age was 60.5 years (35-84). Forty-seven patients (94%) received 54 Gy. Median duration of chemoradiation was 39 days (37-105). Grade 3 and 4 acute toxicity were observed in 66%. Thirty-one percent with severe acute toxicity developed severe late toxicity. Of those who experienced severe late skin toxicity, 29% did not have severe acute toxicity. Disease-free survival at 5 years was 74% (95% confidence interval [CI], 60-84), and at 9 years 61% (95% CI, 46-74). Overall survival at 5 years was 84% (95% CI, 71-92), and at 9 years 67% (95% CI, 50-81). Colostomy-free survival at 5 years was 70% (95% CI, 56-81), and at 9 years 57% (95% CI, 40-72). CONCLUSION: It is feasible to deliver chemoradiation with bolus MMC and protracted infusion FU for anal cancer. Efficacy and toxicity of this regimen seem similar to conventional chemoradiation with FU/MMC. Acute skin toxicity is not a reliable predictor of severe late skin toxicity.
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ItemPrognostic value of tumour regression grade in locally advanced rectal cancer: a systematic review and meta-analysis(WILEY, 2018-07)AIM: The current standard of care for locally advanced rectal cancer involves neoadjuvant chemoradiotherapy (CRT) followed by total mesorectal excision. There is a spectrum of response to neoadjuvant therapy; however, the prognostic value of tumour regression grade (TRG) in predicting disease-free survival (DFS) or overall survival (OS) is inconsistent in the literature. METHOD: This study was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A systematic search was undertaken using Ovid MEDLINE, Embase and Google Scholar. Inclusion criteria were Stage II and III locally advanced rectal cancer treated with long-course CRT followed by radical surgery. The aim of the meta-analysis was to assess the prognostic implication of each TRG for rectal cancer following neoadjuvant CRT. Long-term prognosis was assessed. The main outcome measures were DFS and OS. A random effects model was performed to pool the hazard ratio (HR) from all included studies. RESULTS: There were 4875 patients from 17 studies, with 775 (15.9%) attaining a pathological complete response (pCR) and 719 (29.9%) with no response. A significant association with OS was identified from a pooled-estimated HR for pCR (HR = 0.47, P = 0.002) and nonresponding tumours (HR = 2.97; P < 0.001). Previously known tumour characteristics, such as ypN, lymphovascular invasion and perineural invasion, were also significantly associated with DFS and OS, with estimated pooled HRs of 2.2, 1.4 and 2.3, respectively. CONCLUSION: In conclusion, the degree of TRG was of prognostic value in predicting long-term outcomes. The current challenge is the development of a high-validity tests to predict pCR.
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ItemPhase II trial evaluating the feasibility of interdigitating folfox with chemoradiotherapy in locally advanced and metastatic rectal cancer(NATURE PUBLISHING GROUP, 2014-11-11)BACKGROUND: Patients (pts) with metastatic rectal cancer and symptomatic primary, require local and systemic control. Chemotherapy used during chemoradiotherapy (CRT) is adequate for radiosensitisation, but suboptimal for systemic control. The aim of this phase II study was to assess tolerability, local/systemic benefits, of a novel regimen delivering interdigitating intensive chemotherapy with radical CRT. METHODS: Eligible pts had untreated synchronous symptomatic primary/metastatic rectal cancer. A total of 12 weeks of treatment with split-course pelvic CRT (total 50.4 Gy with concurrent oxaliplatin and 5-FU infusion) alternating with FOLFOX chemotherapy. All pts staged with CT, MRI and FDG-PET pre and post treatment. RESULTS: Twenty-six pts were treated. Rectal primary MRI stage: T3 81% and T4 15%. Liver metastases in 81%. Twenty-four pts (92%) completed the 12-week regimen. All patients received planned RT dose, and for both agents over 88% of patients achieved a relative dose intensity of >75%. Grade 3 toxicities: neutropenia 23%, diarrhoea 15%, and radiation skin reaction 12%. Grade 4 toxicity: neutropenia 15%. FDG-PET metabolic response rate for rectal primary 96%, and for metastatic disease 60%. CONCLUSIONS: Delivery of interdigitating chemotherapy with radical CRT was feasible to treat both primary and metastatic rectal cancer. High completion and response rates were encouraging.
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ItemThe predictive value of PET/CT for distant recurrences in locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy(WILEY, 2021-12)INTRODUCTION: It is well recognized that pathological complete response (pCR) for locally advanced rectal cancer after neoadjuvant chemoradiotherapy (CRT) confers a positive survival advantage. Despite this, a small proportion of patients can develop distant recurrence, and these are the patients that will likely benefit from adjuvant therapy. This study aims to investigate the role of PET/CT as a functional imaging to stratify patients according to their risk of distant recurrence. METHODS: This is a retrospective analysis of a prospectively maintained database in a single quaternary teaching hospital from 2010 to 2019. All consecutive cases of locally advanced rectal cancer with restaging PET/CT were included. The primary outcome measure was 5-year OS and distant recurrence-free survival. RESULTS: A pCR and complete metabolic response (CMR) were identified in 47 (18%) patients and 73 (27.4%) patients respectively. Of these, 26 patients had both pCR and CMR and these patients remained free of local and distant recurrence at their last censored date. Patients with both pCR and CMR achieved the highest 5-year overall survival of 96.2%, followed by those with pCR and incomplete CMR (iCMR) of 85.7%, non-pCR and CMR of 85.1% and non-pCR and iCMR of 83.1%. Independent predictors for 5-year distant recurrence-free survival were pathological and PET metabolic response, nodal staging and lymphovascular invasion (LVI). CONCLUSION: In conclusion, a PET/CT has the potential to better stratify patients of their risk of distant metastasis. However, a larger validation cohort is required before these findings can be translated to clinical utility.