G. Delaney

Prediction of outcome of early ER+ breast cancer is improved using a biomarker panel, which includes Ki-67 and p53

Background:The aim of this study is to determine whether immunohistochemical (IHC) assessment of Ki67 and p53 improves prognostication of oestrogen receptor-positive (ER+) breast cancer after breast-conserving therapy (BCT). In all, 498 patients with invasive breast cancer from a randomised trial of BCT with or without tumour bed radiation boost were assessed using IHC.Methods:The ER+ tumours were classified as ‘luminal A’ (LA): ER+ and/or PR+, Ki-67 low, p53−, HER2− or ‘luminal B’ (LB): ER+ and/or PR+and/or Ki-67 high and/or p53+ and/or HER2+. Kaplan–Meier and Cox proportional hazards methodology were used to ascertain relationships to ispilateral breast tumour recurrence (IBTR), locoregional recurrence (LRR), distant metastasis-free survival (DMFS) and breast cancer-specific survival (BCSS).Results:In all, 73 patients previously LA were re-classified as LB: a greater than four-fold increase (4.6–19.3%) compared with ER, PR, HER2 alone. In multivariate analysis, the LB signature independently predicted LRR (hazard ratio (HR) 3.612, 95% CI 1.555–8.340, P=0.003), DMFS (HR 3.023, 95% CI 1.501–6.087, P=0.002) and BCSS (HR 3.617, 95% CI 1.629–8.031, P=0.002) but not IBTR.Conclusion:The prognostic evaluation of ER+ breast cancer is improved using a marker panel, which includes Ki-67 and p53. This may help better define a group of poor prognosis ER+ patients with a greater probability of failure with endocrine therapy.

Impact of a real-time peer review audit on patient management in a radiation oncology department.

In September 2006, the Royal Australian and New Zealand College of Radiologists (RANZCR) endorsed the modified Peer Review Audit Tool (PRAT). We aimed to assess the feasibility of using this tool in a busy radiation oncology department using an electronic medical record (EMR) system, identify areas of compliance and assess the impact of the audit process on patient management. Fortnightly random clinical audit was undertaken by using the revised RANZCR PRAT in the departments of radiation oncology at Liverpool and Macarthur Cancer Therapy Centres (LCTC and MCTC). Following audit of the EMR, treatment plans were audited by peer review. Data were collected prospectively from June 2007 to June 2008. Audits were carried out on 208 patients. Behaviour criteria were well documented in the EMR, but scanning of histology and medical imaging reports did not occur in up to a third of cases. With electronic prescriptions, treatment prescription errors were rare. In total, 8 (3.8%) out of 208 patients had a change to management recommended. Variability in interpretation of PRAT ‘protocol/study’ criteria was identified. We found that real‐time audit is feasible and effective in detecting both issues with documentation in the EMR, and a small number of patients in whom a change to management is recommended. Recommendations have been made in order to continue to improve the audit process including documentation of any changes recommended and whether the recommended change occurred.

Split-course accelerated therapy in head and neck cancer: An analysis of toxicity

PURPOSE To retrospectively assess a protocol of split-course accelerated radiation therapy (SCAT) for selected head and neck cancers. METHODS AND MATERIALS SCAT consisted of 1.8 Gy per fraction administered twice daily with a minimum gap between fractions of 6 h. The treatment protocol prescribed an initial 16 fractions followed by a planned 5 to 12 day break, and then a further 20 to 22 fractions for a total dose ranging from 64.8 to 72 Gy delivered in 5 to 6 weeks. RESULTS Twenty-eight patients received SCAT for histologically confirmed head and neck cancer between January 1987 and August 1991. All patients were followed up until December 1, 1993. The mean potential follow-up time was 4.2 years (range: 2.9-6.2 years). All patients completed the treatment protocol. Thirteen tumors were laryngeal in origin, eight hypopharyngeal, four paranasal sinus, and three oropharyngeal. There were no Stage I, three Stage II, nine Stage III, and 12 Stage IV tumors. Four tumors were not staged (two paranasal sinus cancers and two surgical recurrences). Early and late toxicities were moderate to severe. Confluent mucositis was experienced by 27 of the 28 patients (96%). One patient required a prolonged midtreatment break of 24 days. Nine patients (32%) required narcotic analgesia for pain relief. Eleven patients (39%) required hospitalization for nasogastric feeding or pain control. The median length of hospital stay was 14 days (range 7-98 days). The actuarial rate of severe late toxicity at 3 years was 47% (standard error (SE) = 13%). A complete tumor response was achieved in 86% of patients. The actuarial local control rate at 3 years was 43% (SE = 11%) and the actuarial survival rate at 3 years was 25% (SE = 8%). CONCLUSION Given the encouraging complete response rate and local control for such advanced tumors, SCAT for locoregionally advanced tumors merits further investigation. However, because of the significant late toxicity observed, the total dose, interfraction interval, and fractionation technique used should be reconsidered.

Rapid learning in practice: A lung cancer survival decision support system in routine patient care data

Background and purpose A rapid learning approach has been proposed to extract and apply knowledge from routine care data rather than solely relying on clinical trial evidence. To validate this in practice we deployed a previously developed decision support system (DSS) in a typical, busy clinic for non-small cell lung cancer (NSCLC) patients. Material and methods Gender, age, performance status, lung function, lymph node status, tumor volume and survival were extracted without review from clinical data sources for lung cancer patients. With these data the DSS was tested to predict overall survival. Results 3919 lung cancer patients were identified with 159 eligible for inclusion, due to ineligible histology or stage, non-radical dose, missing tumor volume or survival. The DSS successfully identified a good prognosis group and a medium/poor prognosis group (2 year OS 69% vs. 27/30%, p < 0.001). Stage was less discriminatory (2 year OS 47% for stage I–II vs. 36% for stage IIIA–IIIB, p = 0.12) with most good prognosis patients having higher stage disease. The DSS predicted a large absolute overall survival benefit (~40%) for a radical dose compared to a non-radical dose in patients with a good prognosis, while no survival benefit of radical radiotherapy was predicted for patients with a poor prognosis. Conclusions A rapid learning environment is possible with the quality of clinical data sufficient to validate a DSS. It uses patient and tumor features to identify prognostic groups in whom therapy can be individualized based on predicted outcomes. Especially the survival benefit of a radical versus non-radical dose predicted by the DSS for various prognostic groups has clinical relevance, but needs to be prospectively validated.

Three-dimensional dose distribution of tangential breast irradiation: results of a multicentre phantom dosimetry study

BACKGROUND AND PURPOSE One aspect of good radiotherapeutic practice is to achieve dose homogeneity. Dose inhomogeneities occur with breast tangent irradiation, particularly in women with large breasts. MATERIALS AND METHODS Ten Australian radiation oncology centres agreed to participate in this multicentre phantom dosimetry study. An Alderson radiation therapy anthropomorphic phantom with attachable breasts of two different cup sizes (B and DD) was used. The entire phantom was capable of having thermoluminescent dosimeters (TLD) material inserted at various locations. Nine TLD positions were distributed throughout the left breast phantom including the superior and inferior planes. The ten centres were asked to simulate, plan and treat (with a prescription of 100 cGy) the breast phantoms according to their standard practice. Point doses from resultant computer plans were calculated for each TLD position. Measured and calculated (planning computer) doses were compared. RESULTS The dose planning predictability between departments did not appear to be significantly different for both the small and large breast phantoms. The median dose deviation (calculated dose minus measured dose) for all centres ranged from 2. 3 to 5.3 cGy on the central axis and from 2.1 to 7.5 cGy for the off-axis planes. The highest absolute dose was measured in the inferior plane of the large breast (128.7 cGy). The greatest dose inhomogeneity occurred in the small breast phantom volume (median range 93.2-105 cGy) compared with the large breast phantom volume (median range, 100.1-107.7 cGy). There was considerable variation in the use (or not) of wedges to obtain optimized dosimetry. No department used 3D compensators. CONCLUSION The results highlight areas of potential improvement in the delivery of breast tangent radiotherapy. Despite reasonable dose predictability, the greatest dose deviation and highest measured doses occurred in the inferior aspects of both the small and large breast phantoms.

Australian survey on current practices for breast radiotherapy

Detailed, published surveys specific to Australian breast radiotherapy practice were last conducted in 2002. More recent international surveys specific to breast radiotherapy practice include a European survey conducted in 2008/2009 and a Spanish survey conducted in 2009. Radiotherapy techniques continue to evolve, and the utilisation of new techniques, such as intensity‐modulated radiation therapy (IMRT), is increasing. This survey aimed to determine current breast radiotherapy practices across Australia.

A comparison of surgical and radiotherapy breast cancer therapy utilization in Canada (British Columbia), Scotland (Dundee), and Australia (Western Australia) with models of “optimal” therapy

BACKGROUND Different jurisdictions report different breast cancer treatment rates. Evidence-based utilization models may be specific to derived populations. We compared predicted optimal with actual radiotherapy utilization in British Columbia, Canada; Dundee, Scotland; and Perth, Western Australia. DESIGN Data were analyzed for differences in demography, tumor, and treatment. Epidemiological data were fitted to published Australian optimal radiotherapy utilization trees and region-specific optimal treatment rates were calculated. Optimal and actual surgery/radiotherapy rates from 2 population-based and 1 institution-based registries were compared for patients diagnosed with breast cancer between 2000 and 2004, and 2002 for British Columbia. RESULTS Mastectomy rates differed between British Columbia (40%), Western Australia (44%), and Dundee (47%, p<0.01). Radiotherapy rates differed between British Columbia (60%), Western Australia (52%), and Dundee (49%, p<0.01). Actual radiotherapy utilization rates were lower than optimal estimates. Region-specific optimal utilization rates at diagnosis varied from 57% to 71% for radiotherapy and 62% to 64% when taking into account patient preference. Variation was attributed to local differences in demography and tumor stage. CONCLUSIONS Actual treatment rates varied, and were associated with patterns of care and guideline differences. Actual radiotherapy rates were lower than optimal rates. Differences between optimal and actual utilization may be due to access shortfalls, and patient preference.

A comparison of systemic breast cancer therapy utilization in Canada (British Columbia), Scotland (Dundee), and Australia (Western Australia) with models of “optimal” therapy

BACKGROUND Different jurisdictions report different breast cancer treatment rates. Evidence-based optimal utilization models may be specific to the derived population. We compared predicted optimal with actual endocrine and chemotherapy utilization in British Columbia, Canada; Dundee, Scotland; and Perth, Western Australia. DESIGN Data were analyzed for differences in demography, tumour, and treatment. Epidemiological data were fitted to published Australian optimal radiotherapy utilization trees and region-specific optimal treatment rates were calculated. Optimal and actual systemic therapy rates from 2 population-based and 1 institution-based cancer registries were compared for patients diagnosed with breast cancer between 2000-2004, and 2002 for British Columbia. RESULTS Chemotherapy rates differed between British Columbia (32%), Perth (29%), and Dundee (24%, p = 0.014). Endocrine therapy rates were similar between British Columbia (56%), Perth (59%), and Dundee (64%, p > 0.05). Actual utilization rates were lower than optimal estimates for chemotherapy, but higher for endocrine therapy. Region-specific optimal utilization rates at diagnosis varied between 50-56% for chemotherapy, and 49-54% for endocrine therapy. Variation was attributed to local differences in demographics, and tumour stage. CONCLUSION Actual treatment rates varied. There was lower than estimated optimal chemotherapy use but higher than expected use of endocrine therapy.

Estimation of the Optimal Brachytherapy Utilization Rate in the Treatment of Gynecological Cancers and Comparison With Patterns of Care

PURPOSE We aimed to estimate the optimal proportion of all gynecological cancers that should be treated with brachytherapy (BT)-the optimal brachytherapy utilization rate (BTU)-to compare this with actual gynecological BTU and to assess the effects of nonmedical factors on access to BT. METHODS AND MATERIALS The previously constructed inter/multinational guideline-based peer-reviewed models of optimal BTU for cancers of the uterine cervix, uterine corpus, and vagina were combined to estimate optimal BTU for all gynecological cancers. The robustness of the model was tested by univariate and multivariate sensitivity analyses. The resulting model was applied to New South Wales (NSW), the United States, and Western Europe. Actual BTU was determined for NSW by a retrospective patterns-of-care study of BT; for Western Europe from published reports; and for the United States from Surveillance, Epidemiology, and End Results data. Differences between optimal and actual BTU were assessed. The effect of nonmedical factors on access to BT in NSW were analyzed. RESULTS Gynecological BTU was as follows: NSW 28% optimal (95% confidence interval [CI] 26%-33%) compared with 14% actual; United States 30% optimal (95% CI 26%-34%) and 10% actual; and Western Europe 27% optimal (95% CI 25%-32%) and 16% actual. On multivariate analysis, NSW patients were more likely to undergo gynecological BT if residing in Area Health Service equipped with BT (odds ratio 1.76, P=.008) and if residing in socioeconomically disadvantaged postcodes (odds ratio 1.12, P=.05), but remoteness of residence was not significant. CONCLUSIONS Gynecological BT is underutilized in NSW, Western Europe, and the United States given evidence-based guidelines. Access to BT equipment in NSW was significantly associated with higher utilization rates. Causes of underutilization elsewhere were undetermined. Our model of optimal BTU can be used as a quality assurance tool, providing an evidence-based benchmark against which actual patterns of practice can be measured. It can also be used to assist in determining the adequacy of BT resource allocation.

Estimation of the optimal brachytherapy utilisation rate in the treatment of vaginal cancer and comparison with patterns of care

Introduction: Having previously modelled the optimal proportion of uterine cervix and corpus cancers that should be treated with brachytherapy (BT), we aimed to complete the assessment of the role of BT for gynaecological cancers by estimating the optimal proportion of vaginal cancer cases that should be treated with BT, the optimal BT utilisation (BTU) rate for vaginal cancer. We compared this with actual vaginal BTU and assessed quality of BT for vaginal cancer by a Patterns‐of‐Care Study (POCS).