About 125,000 people are diagnosed with cancer in Australia each year. With population growth and aging this is set to rise to 150,000 new cases each year by 2020.1 in 2 Australian men and 1 in 3 Australian women will be diagnosed with cancer by the age of 85. Cancer is a leading cause of death in Australia. (Source: Cancer Council Australia)
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Latest Research Publications
Safe handling and administration of MABS: the guidance.
Br J Nurs. 2015; 24(16 Suppl 1):S14-20 [PubMed] Related Publications
Benefit Cost Analysis of Three Skin Cancer Public Education Mass-Media Campaigns Implemented in New South Wales, Australia.
PLoS One. 2016; 11(1):e0147665 [PubMed] Free Access to Full Article Related Publications
Timeliness of lung cancer care in Victoria: a retrospective cohort study.
Med J Aust. 2016; 204(2):75.e1-9 [PubMed] Related Publications
DESIGN, SETTING AND PARTICIPANTS: A retrospective cohort study, conducted in six public and two private Victorian hospitals, of 1417 patients aged 18 years or more who were diagnosed between July 2011 and October 2014 with an incident case of lung cancer identified by International Classification of Diseases, 10th revision codes (C34.0-C34.9, Z85.1, Z85.2) on the basis of either a clinical or pathological diagnosis.
OUTCOME MEASURES: Time intervals between referral, diagnosis and initial definitive management.
RESULTS: The median time from referral to diagnosis was 15 days (interquartile range [IQR], 5-36); from diagnosis to initial definitive management, 30 days (IQR, 6-84); and from referral to initial definitive management, 53 days (IQR, 25-106). Factors that were significantly associated with delay between referral and initial definitive management include declining or not being referred to palliative care (hazard ratio [HR], v patients referred for palliation, 0.73; 95% CI, 0.62-0.86; P < 0.001), and being treated in a public hospital (HR, v patients managed in a private hospital, 0.55; 95% CI, 0.48-0.64; P < 0.001). The median time from referral to initial definitive management in public and private hospitals was 61 days (IQR, 35-118) and 30 days (IQR, 13-76) respectively; 48% of patients in public hospitals waited longer than the British National Health Service target of a maximum 62 days between referral and first definitive treatment.
CONCLUSION: There are significant delays at various stages of the patient journey after referral for initial definitive management. Having a greater understanding of these delays will enable strategies to be developed that improve the timeliness of care for patients with lung cancer.
Incidence and survival trends for malignant pleural and peritoneal mesothelioma, Australia, 1982-2009.
Occup Environ Med. 2016; 73(3):187-94 [PubMed] Related Publications
METHODS: Data on 10 930 people with malignant pleural mesothelioma (MPM) and 640 people with malignant peritoneal mesothelioma diagnosed in Australia during 1982-2009 were analysed. Observed incidence rate trends were quantified. Incidence rates were projected up to 2030 using observed incident cases during 1982-2012. The relative per-decade change in excess mortality during 1999-2009 was estimated.
RESULTS: During 1982-2009, acceleration in MPM age-standardised incidence rates were highest for women and those aged 75 years and above, with average annual percentage changes of +4.9 (95% CI 3.6 to 6.2) and +7.2 (95% CI 5.4 to 9.0), respectively. Age-standardised incidence rates for men with MPM aged 0-64 years decelerated rapidly during 2003-2009, an average annual percentage change of -5.1% (95% CI -7.6% to -2.5%). Overall, male age-specific MPM incidence rates in the age group of 65-74 year during 2010-2030 are projected to decline with rates projected to increase for older men and women with MPM. There was a statistically significant 16% relative reduction in the excess mortality rate (EMR) up to 5 years postdiagnosis for people diagnosed with malignant pleural and peritoneal mesothelioma combined in 2009 compared with those diagnosed in 1999, an EMR ratio of 0.84 (95% CI 0.77 to 0.92).
CONCLUSIONS: Australia's malignant mesothelioma incidence rates appear to have reached maximum levels but with differences over time by age, gender and tumour location. Improvements over time in survival provide a glimpse of hope for this almost invariably fatal disease.
Apple intake is inversely associated with all-cause and disease-specific mortality in elderly women.
Br J Nutr. 2016; 115(5):860-7 [PubMed] Related Publications
The impact on health-related quality of life in the first 12 months: A randomised comparison of preoperative short-course radiation versus long-course chemoradiation for T3 rectal cancer (Trans-Tasman Radiation Oncology Group Trial 01.04).
Eur J Cancer. 2016; 55:15-26 [PubMed] Related Publications
PATIENTS AND METHODS: Eligible patients with T3N0-2M0 rectal cancer completed the European Organisation for Research and Treatment of Cancer quality of life questionnaire (QLQ-C30) and the colorectal cancer specific module (QLQ C38) at randomisation and 1, 2, 3, 6, 9 and 12 months later.
RESULTS: Of 326 patients randomised, 297 (SC 143, LC 154) were eligible for completion of HRQOL questionnaires. Baseline scores were comparable across the SC and LC groups. Patients reported low scores on sexual functioning and sexual enjoyment. Defaecation problems were the worst of the symptoms at baseline. Surgery had the most profoundly negative effect on HRQOL, seen in both the SC and LC treatment groups to the same extent. The most severely affected domains were physical function and role function and the most severely affected symptoms were fatigue, pain, appetite, weight loss and male sexual problems. Most domains and symptoms returned to baseline levels by 12 months apart from body image, sexual enjoyment and male sexual problems. Future perspective was better than prior to treatment.
CONCLUSION: There is no overall difference in HRQOL between SC and LC neoadjuvant treatment strategies, in the first 12 months, after surgery. In the immediate postoperative period HRQOL was adversely affected in both groups but for the most part was temporary. Some residual sexual functioning concerns persisted at 12 months.
Loss of BAP1 Expression Occurs Frequently in Intrahepatic Cholangiocarcinoma.
Medicine (Baltimore). 2016; 95(2):e2491 [PubMed] Free Access to Full Article Related Publications
EFFECTS OF COMPRESSION ON LYMPHEDEMA DURING RESISTANCE EXERCISE IN WOMEN WITH BREAST CANCER-RELATED LYMPHEDEMA: A RANDOMIZED, CROSS-OVER TRIAL.
Lymphology. 2015; 48(2):80-92 [PubMed] Related Publications
Lateral pelvic compartment excision during pelvic exenteration.
Br J Surg. 2015; 102(13):1710-7 [PubMed] Related Publications
METHODS: Patients undergoing pelvic exenteration between 1994 and 2014 were eligible for review.
RESULTS: Two hundred consecutive patients who had en bloc resection of the lateral compartment were included. R0 resection was achieved in 66·5 per cent of 197 patients undergoing surgery for cancer and 68·9 per cent of planned curative resections. For patients with colorectal cancer, a clear resection margin was associated with a significant overall survival benefit (P = 0·030). Median overall and disease-free survival in this group was 41 and 27 months respectively. Overall 1-, 3- and 5-year survival rates were 86, 46 and 35 per cent respectively. No predictors of survival were identified on univariable analysis other than margin status and operative intent. Excision of the common or external iliac vessels or sciatic nerve did not confer a survival disadvantage.
CONCLUSION: The continuing evolution of radical pelvic exenteration techniques has seen an improvement in R0 margin status from 21 to 66·5 per cent over a 20-year interval by routine adoption of a more lateral anatomical plane. Five-year overall survival rates are comparable with those for more centrally based tumours.
Olfactory Neuroblastoma: Fate of the Neck--A Long-term Multicenter Retrospective Study.
Otolaryngol Head Neck Surg. 2016; 154(2):383-9 [PubMed] Related Publications
STUDY DESIGN: Multicenter case series with retrospective chart review.
SETTING AND SUBJECTS: In sum, 113 patients with a histopathologic diagnosis of olfactory neuroblastoma across 6 tertiary hospitals in Australia and the United States.
METHODS: Treatment modalities for the primary site and neck included surgery, radiotherapy, and combined therapy. Treatment outcomes were measured in relation to date of primary treatment, and long-term follow-up was recorded. Disease-free survival was calculated as time for patients to develop delayed neck disease following primary treatment.
RESULTS: A total of 113 patients (46 females, 49.7 ± 13.2 years) were identified with a median follow-up of 41.5 months (interquartile range, 58.2); 7.1% of patients presented with primary neck disease, while 8.8% of patients presented with delayed neck disease. Neck disease was present in patients with Hyams grade II (22.2%), III (55.6%), and IV (22.2%) lesions (χ(2) = 5.66, P = .13). Histologic grade was higher in patients with primary neck disease (χ(2) = 16.22, P = .001). Positive surgical margins were associated with a higher risk of delayed neck disease as compared with clear surgical margin (17.9% vs 5%, P = .034).
CONCLUSION: Neck metastasis is an important clinical consideration for olfactory neuroblastoma at presentation and in surveillance. Primary treatment of the neck could be considered in select patients. Long-term surveillance of the neck and primary site is essential.
Spontaneous regression of CIN2 in women aged 18-24 years: a retrospective study of a state-wide population in Western Australia.
Acta Obstet Gynecol Scand. 2016; 95(3):291-8 [PubMed] Related Publications
MATERIAL AND METHODS: A retrospective cohort study of Western Australian women aged 18-24 years diagnosed with CIN2 on cervical biopsy from 1 January 2001 to 31 December 2010. Women who had not received treatment at ≥4 months following CIN2 diagnosis were classified as managed 'conservatively'. Subsequent cervical cytology and/or biopsy test results were used to report lesion regression (absence of dysplasia or an epithelial lesion of lower grade than CIN2) and disease persistence (CIN2, CIN3 or ACIS).
RESULTS: Follow-up data were available for 2417 women of whom 924 (38.2%) were 'conservatively' managed. In all, 152 (16.4%) conservatively managed women had a lesion more severe than CIN2 detected within 24 months of initial diagnosis, of which 144 were CIN3 and eight were ACIS. There was no statistically significant association between rates of regression and patient age, Socio-economic Indexes for Areas or Accessibility/Remoteness Index of Australia indices. The 2-year regression rate for CIN2 was estimated to be 59.5% (95%CI 0.5-0.6) in this cohort of women.
CONCLUSION: In conservatively managed young women with CIN2 there was a high rate of spontaneous disease regression. Thus, excisional or ablative treatments may be avoided in selected patients who receive appropriate counseling and who are able to comply with more intensive and prolonged follow-up requirements.
The Value of Audio Devices in the Endoscopy Room (VADER) study: a randomised controlled trial.
Med J Aust. 2015; 203(11):472-5 [PubMed] Related Publications
DESIGN AND SETTING: A single-centre, prospective, randomised controlled trial conducted in an endoscopy suite within a quaternary-centre gastroenterology unit, Melbourne, Australia.
MAIN OUTCOME MEASURES: The primary outcome measures were procedure time, polyp detection rate (PDR) and adenoma detection rate (ADR). The secondary outcome measure was adenomas per colonoscopy (APC).
RESULTS: 103 colonoscopies were analysed: 58 in the SWM group and 45 in the PM group. Bowel preparation was assessed as good or excellent in 57% of the SWM group compared with 69% of the PM group (P < 0.01). The PDR was significantly higher in the SWM group than in the PM group (60% v 35%; P = 0.006). Similarly, the ADR was significantly higher in the SWM group than in the PM group (48% v 27%; P = 0.01). The APC in the SWM group was 84% compared with 35% in the PM group (P = 0.01).
CONCLUSION: SWM compared with PM improves key quality outcomes in colonoscopy, despite poorer bowel preparation.
HER2 Codon 655 (Ile/Val) Polymorphism and Breast Cancer in Austrian Women.
Anticancer Res. 2015; 35(12):6667-70 [PubMed] Related Publications
MATERIALS AND METHODS: We studied the HER2 codon 655 (rs1136201) polymorphism in 80 Austrian patients with BC and 100 healthy volunteers by pyrosequencing and polymerase chain reaction. Associations between codon 655 allelic variants and clinicopathological variables (e.g. age, stage of disease, tumor type, grading, and receptor status) were studied with 2×2 tables.
RESULTS: The genotypic distributions in patients with BC (AA: 63.75%, AG: 32.5%, GG: 3.75%) and controls (AA: 63%, AG: 34%, GG: 3.7%) were virtually identical (odds ratio=1.03, 95% confidence interval=0.56-1.90). A non-significant link between carrying at least one G allele and more aggressive tumor type (estrogen receptor-negative p=0.08, G3 tumor p=0.19) was observed.
CONCLUSION: Genotypic variation within the codon 655 of HER2 does not alter the BC risk in Caucasian Austrian women. The association between the G allele and more aggressive tumor types requires further investigation.
Differences in the Pathological Diagnosis and Repeat Craniotomy Rates in Cerebral Tumors Undergoing Biopsy or Resection in an Urban Versus Regional Center.
Medicine (Baltimore). 2015; 94(47):e2131 [PubMed] Related Publications
Geographic variation in the intended choice of adjuvant treatments for women diagnosed with screen-detected breast cancer in Queensland.
BMC Public Health. 2015; 15:1204 [PubMed] Free Access to Full Article Related Publications
METHODS: Linked population-based datasets from BreastScreen Queensland and the Queensland Cancer Registry during 1997-2008 for women aged 40-89 years were used. We adopted a Bayesian shared spatial component model to evaluate the relative intended use of each adjuvant therapy across 478 areas as well as common spatial patterns between treatments.
RESULTS: Women living closer to a cancer treatment facility were more likely to intend to use adjuvant therapy. This was particularly marked for radiotherapy when travel time to the closest radiation facility was 4 + h (OR =0.41, 95 % CrI: [0.23, 0.74]) compared to <1 h. The shared spatial effect increased towards the centres with concentrations of radiotherapy facilities, in north-east (Townsville) and south-east (Brisbane) regions of Queensland. Moreover, the presence of residual shared spatial effects indicates that there are other unmeasured geographical barriers influencing women's treatment choices.
CONCLUSIONS: This highlights the need to identify the additional barriers that impact on treatment intentions among women diagnosed with screen-detected breast cancer, particularly for those women living further away from cancer treatment centers.
Hypertension, antihypertensive treatment and cancer incidence and mortality: a pooled collaborative analysis of 12 Australian and New Zealand cohorts.
J Hypertens. 2016; 34(1):149-55 [PubMed] Related Publications
METHOD: Eighty-six thousand five hundred and ninety-three participants from the Australian and New Zealand Diabetes and Cancer Collaboration were linked to the National Death Index and Australian Cancer Database. Cox proportional hazards models estimated hazard ratios and 95% confidence intervals (95% CI) for the association of treated and untreated hypertension with cancer incidence and mortality.
RESULTS: Over a median follow-up of 15.1 years, 12 070 incident and 4350 fatal cancers were identified. Untreated and treated hypertension, compared with normotension, were associated with an increased risk for cancer incidence [hazard ratio 1.06, 95% CI (1.00-1.11) and 1.09 (1.02-1.16) respectively], and cancer mortality (1.07, 0.98-1.18) and (1.15, 1.03-1.28), respectively. When compared with untreated hypertension, treated hypertension did not have a significantly greater risk for cancer incidence (1.03, 0.97-1.10) or mortality (1.07, 0.97-1.19). A significant dose-response relationship was observed between graded hypertension and cancer incidence and mortality; Ptrend = 0.053 and Ptrend = 0.001, respectively. When stratified by treatment status, these relationships remained significant in untreated, but not in treated, hypertension.
CONCLUSION: Hypertension, both treated and untreated, is associated with a modest increased risk for cancer incidence and mortality. Similar risks in treated and untreated hypertension suggest that the increased cancer risk is not explained by the use of antihypertensive treatment.
Acquired BRAF inhibitor resistance: A multicenter meta-analysis of the spectrum and frequencies, clinical behaviour, and phenotypic associations of resistance mechanisms.
Eur J Cancer. 2015; 51(18):2792-9 [PubMed] Article available free on PMC after 01/12/2016 Related Publications
METHODS: We compiled clinical and genetic data from 100 patients with 132 tissue samples obtained at progression on BRAFi therapy from 3 large, previously published studies of BRAFi resistance. These samples were subjected to whole-exome sequencing and/or polymerase chain reaction-based genetic testing.
RESULTS: Among 132 samples, putative resistance mechanisms were identified in 58%, including NRAS or KRAS mutations (20%), BRAF splice variants (16%), BRAF(V600E/K) amplifications (13%), MEK1/2 mutations (7%), and non-mitogen-activated protein kinase pathway alterations (11%). Marked heterogeneity was observed within tumors and patients; 18 of 19 patients (95%) with more than one progression biopsy had distinct/unknown drivers of resistance between samples. NRAS mutations were associated with vemurafenib use (p = 0.045) and intracranial metastases (p = 0.036), and MEK1/2 mutations correlated with hepatic progression (p = 0.011). Progression-free survival and overall survival were similar across resistance mechanisms. The median survival after disease progression was 6.9 months, and responses to subsequent BRAF and MEK inhibition were uncommon (2 of 15; 13%). Post-progression outcomes did not correlate with specific acquired BRAFi-resistance mechanisms.
CONCLUSIONS: This is the first study to systematically characterise the clinical implications of particular acquired BRAFi-resistance mechanisms in patients with BRAF-mutant melanoma largest study to compile the landscape of resistance. Despite marked heterogeneity of resistance mechanisms within patients, NRAS mutations correlated with vemurafenib use and intracranial disease involvement.
In the digital era, architectural distortion remains a challenging radiological task.
Clin Radiol. 2016; 71(1):e35-40 [PubMed] Related Publications
MATERIALS AND METHODS: Forty-one experienced breast screen readers (20 US and 21 Australian) were asked to read a single test set of 30 digitally acquired mammographic cases. Twenty cases had abnormal findings (10 with AD, 10 non-AD) and 10 cases were normal. Each reader was asked to locate and rate any abnormalities. Lesion and case-based performance was assessed. For each collection of readers (US; Australian; combined), jackknife free-response receiver operating characteristic (JAFROC), figure of merit (FOM), and inferred receiver operating characteristic (ROC), area under curve (Az) were calculated using JAFROC v.4.1 software. Readers' sensitivity, location sensitivity, JAFROC, FOM, ROC, Az scores were compared between cases groups using Wilcoxon's signed ranked test statistics.
RESULTS: For lesion-based analysis, significantly lower location sensitivity (p=0.001) was shown on AD cases compared with non-AD cases for all reader collections. The case-based analysis demonstrated significantly lower ROC Az values (p=0.02) for the first collection of readers, and lower sensitivity for the second collection of readers (p=0.04) and all-readers collection (p=0.008), for AD compared with non-AD cases.
CONCLUSIONS: The current work demonstrates that AD remains a challenging task for readers, even in the digital era.
The effects of age on health-related quality of life in cancer populations: A pooled analysis of randomized controlled trials using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 involving 6024 cancer patients.
Eur J Cancer. 2015; 51(18):2808-19 [PubMed] Related Publications
METHODS: Data from 25 EORTC randomized controlled trials was pooled. EORTC QLQ-C30 mean scores for the cancer cohort and five general population cohorts were compared to assess the impact of cancer on patients' HRQOL. Within the cancer cohort, multiple linear regressions (two-sided level P-value = 0.05 adjusted for multiple testing.) were used to investigate the association between age and HRQOL, adjusted for gender, WHO performance status (PS), distant metastasis and stratified by cancer site. A difference of 10 points on the 0-100 scale was considered clinically important.
RESULTS: Cancer patients generally have worse HRQOL compared to the general population, but the specific HRQOL domains impaired vary with age. When comparing the cancer versus the general population, young cancer patients had worse financial problems, social and role functioning, while the older cancer groups had more appetite loss. Within the cancer cohort, HRQOL was worse with increasing age for physical functioning and constipation, and better with increasing age for social functioning, insomnia and financial problems (all p < 0.05).
CONCLUSION: HRQOL is impaired in cancer patients compared to the general population, but the impact on specific HRQOL domains varies by age. Within the cancer population, some HRQOL components improve with age while others deteriorate. Optimal care for older cancer patients should target HRQOL domains most relevant to this population.
Frequency of residual melanoma in wide local excision (WLE) specimens after complete excisional biopsy.
J Am Acad Dermatol. 2016; 74(1):102-7 [PubMed] Related Publications
METHODS: This was a retrospective review of 807 consecutive WLEs of melanomas diagnosed after complete excisional biopsy. All specimens were reviewed by a single dermatopathologist. Risk of residual or locally metastatic disease was analyzed using univariate and multivariate logistic regression models.
RESULTS: In the 807 WLE specimens, further melanoma was found in 34 cases (4.2%; 95% confidence interval [CI] 2.9-5.8). Residual primary melanoma was found in 33 of these. On univariate analysis, features associated with residual or locally metastatic disease were histologic subtype (odds ratio 3.0; 95% CI 1.3-7.1, P = .01) and tumor location (odds ratio 7.3; 95% CI 2.0-26.6, P < .01). On multivariate analysis, lentigo maligna was independently associated with melanoma remaining in WLE specimens (odds ratio 2.7; 95% CI 1.0-7.3, P = .04).
CONCLUSION: Residual melanoma in WLE specimens after histologically assessed complete excisional biopsy is not uncommon. Patients with lentigo maligna subtype melanomas are most at risk. Our findings indicate that the procedure of WLE is most important therapeutically for its role in controlling the primary tumor, rather than in preventing local metastatic recurrence.
Menopausal hormone therapy use and breast cancer risk in Australia: Findings from the New South Wales Cancer, Lifestyle and Evaluation of Risk study.
Int J Cancer. 2016; 138(8):1905-14 [PubMed] Related Publications
Chemotherapy plus lenalidomide versus autologous transplantation, followed by lenalidomide plus prednisone versus lenalidomide maintenance, in patients with multiple myeloma: a randomised, multicentre, phase 3 trial.
Lancet Oncol. 2015; 16(16):1617-29 [PubMed] Related Publications
METHODS: We did an open-label, randomised, multicentre, phase 3 study at 59 centres in Australia, Czech Republic, and Italy. We enrolled transplant-eligible patients with newly diagnosed myeloma aged 65 years or younger. Patients received a common induction with four 28-day cycles of lenalidomide (25 mg, days 1-21) and dexamethasone (40 mg, days 1, 8, 15, and 22) and subsequent chemotherapy with cyclophosphamide (3 g/m(2)) followed by granulocyte colony-stimulating factor for stem-cell mobilisation and collection. Using a 2 × 2 partial factorial design, we randomised patients to consolidation with either chemotherapy plus lenalidomide (six cycles of cyclophosphamide [300 mg/m(2), days 1, 8, and 15], dexamethasone [40 mg, days 1, 8, 15, and 22], and lenalidomide [25 mg, days 1-21]) or two courses of high-dose melphalan (200 mg/m(2)) and ASCT. We also randomised patients to maintenance with lenalidomide (10 mg, days 1-21) plus prednisone (50 mg, every other day) or lenalidomide alone. A simple randomisation sequence was used to assign patients at enrolment into one of the four groups (1:1:1:1 ratio), but the treatment allocation was disclosed only when the patient reached the end of the induction and confirmed their eligibility for consolidation. Both the patient and the treating clinician did not know the consolidation and maintenance arm until that time. The primary endpoint was progression-free survival assessed by intention-to-treat. The trial is ongoing and some patients are still receiving maintenance. This study is registered at ClinicalTrials.gov, number NCT01091831.
FINDINGS: 389 patients were enrolled between July 6, 2009, and May 6, 2011, with 256 eligible for consolidation (127 high-dose melphalan and ASCT and 129 chemotherapy plus lenalidomide) and 223 eligible for maintenance (117 lenalidomide plus prednisone and 106 lenalidomide alone). Median follow-up was 52·0 months (IQR 30·4-57·6). Progression-free survival during consolidation was significantly shorter with chemotherapy plus lenalidomide compared with high-dose melphalan and ASCT (median 28·6 months [95% CI 20·6-36·7] vs 43·3 months [33·2-52·2]; hazard ratio [HR] for the first 24 months 2·51, 95% CI 1·60-3·94; p<0·0001). Progression-free survival did not differ between maintenance treatments (median 37·5 months [95% CI 27·8-not evaluable] with lenalidomide plus prednisone vs 28·5 months [22·5-46·5] with lenalidomide alone; HR 0·84, 95% CI 0·59-1·20; p=0·34). Fewer grade 3 or 4 adverse events were recorded with chemotherapy plus lenalidomide than with high-dose melphalan and ASCT; the most frequent were haematological (34 [26%] of 129 patients vs 107 [84%] of 127 patients), gastrointestinal (six [5%] vs 25 [20%]), and infection (seven [5%] vs 24 [19%]). Haematological serious adverse events were reported in two (2%) patients assigned chemotherapy plus lenalidomide and no patients allocated high-dose melphalan and ASCT. Non-haematological serious adverse events were reported in 13 (10%) patients assigned chemotherapy plus lenalidomide and nine (7%) allocated high-dose melphalan and ASCT. During maintenance, adverse events did not differ between groups. The most frequent grade 3 or 4 adverse events were neutropenia (nine [8%] of 117 patients assigned lenalidomide plus prednisone vs 14 [13%] of 106 allocated lenalidomide alone), infection (eight [8%] vs five [5%]), and systemic toxicities (seven [6%] vs two [2%]). Non-haematological serious adverse events were reported in 13 (11%) patients assigned lenalidomide plus prednisone versus ten (9%) allocated lenalidomide alone. Four patients died because of adverse events, three from infections (two during induction and one during consolidation) and one because of cardiac toxic effects.
INTERPRETATION: Consolidation with high-dose melphalan and ASCT remains the preferred option in transplant-eligible patients with multiple myeloma, despite a better toxicity profile with chemotherapy plus lenalidomide.
Comparison of Prediction Models for Lynch Syndrome Among Individuals With Colorectal Cancer.
J Natl Cancer Inst. 2016; 108(2) [PubMed] Article available free on PMC after 01/02/2017 Related Publications
METHODS: Pedigree data from CRC patients in 11 North American, European, and Australian cohorts (6 clinic- and 5 population-based sites) were used to calculate predicted probabilities of pathogenic MLH1, MSH2, or MSH6 gene mutations by each model and gene-specific predictions by MMRPro and PREMM1,2,6. We examined discrimination with area under the receiver operating characteristic curve (AUC), calibration with observed to expected (O/E) ratio, and clinical usefulness using decision curve analysis to select patients for further evaluation. All statistical tests were two-sided.
RESULTS: Mutations were detected in 539 of 2304 (23%) individuals from the clinic-based cohorts (237 MLH1, 251 MSH2, 51 MSH6) and 150 of 3451 (4.4%) individuals from the population-based cohorts (47 MLH1, 71 MSH2, 32 MSH6). Discrimination was similar for clinic- and population-based cohorts: AUCs of 0.76 vs 0.77 for MMRPredict, 0.82 vs 0.85 for MMRPro, and 0.85 vs 0.88 for PREMM1,2,6. For clinic- and population-based cohorts, O/E deviated from 1 for MMRPredict (0.38 and 0.31, respectively) and MMRPro (0.62 and 0.36) but were more satisfactory for PREMM1,2,6 (1.0 and 0.70). MMRPro or PREMM1,2,6 predictions were clinically useful at thresholds of 5% or greater and in particular at greater than 15%.
CONCLUSIONS: MMRPro and PREMM1,2,6 can well be used to select CRC patients from genetics clinics or population-based settings for tumor and/or germline testing at a 5% or higher risk. If no MMR deficiency is detected and risk exceeds 15%, we suggest considering additional genetic etiologies for the cause of cancer in the family.
Do teleoncology models of care enable safe delivery of chemotherapy in rural towns?
Med J Aust. 2015; 203(10):406-6.e6 [PubMed] Related Publications
DESIGN: A quasi-experimental design comparing two patient groups.
SETTING: TCC and Mount Isa Hospital, which both operate under the auspices of the Townsville Teleoncology Network (TTN).
PARTICIPANTS: Eligible patients who received chemotherapy at TCC or Mt Isa Hospital between 1 May 2007 and 30 April 2012.
INTERVENTION: Teleoncology model for managing cancer patients in rural towns.
MAIN OUTCOME MEASURES: Dose intensity (doses, number of cycles and lines of treatment) and toxicity rates (rate of serious side effects, hospital admissions and mortality).
RESULTS: Over 5 years, 89 patients received a total of 626 cycles of various chemotherapy regimens in Mount Isa. During the same period, 117 patients who received a total of 799 cycles of chemotherapy at TCC were eligible for inclusion in the comparison group. There were no significant differences between the Mount Isa and TCC patients in most demographic characteristics, mean numbers of treatment cycles, dose intensities, proportions of side effects, and hospital admissions. There were no toxicity-related deaths in either group.
CONCLUSION: It appears safe to administer chemotherapy in rural towns under the supervision of medical oncologists from larger centres via teleoncology, provided that rural health care resources and governance arrangements are adequate.
Life expectancy discussions in a multisite sample of Australian medical oncology outpatients.
Med J Aust. 2015; 203(10):405-5.e7 [PubMed] Related Publications
DESIGN: Cross-sectional survey.
SETTING: Eleven large Australian medical oncology treatment centres.
PARTICIPANTS: A total of 1431 medical oncology outpatients participated (81% consent rate). Eligible patients were approached between September 2012 and May 2014.
MAIN OUTCOME MEASURES: Patients indicated whether the information about life expectancy they received aligned with their preferences.
RESULTS: Almost one in four patients (24%) received too little information, 4% received too much, and 50% received all the information they wanted; 22% of patients neither wanted nor received information about life expectancy. Patients were more likely to receive too little information if they were not in remission (odds ratio [OR], 1.77), did not know their cancer stage at diagnosis (OR, 3.64), or were anxious (OR, 1.48) or depressed (OR, 1.48). Patients had greater odds of receiving too much information if they were younger (OR, 1.45), had more advanced cancer (OR, 2.01) or did not know their cancer stage at diagnosis (OR, 4.42).
CONCLUSIONS: That fact that 28% of cancer patients did not receive their desired level of information about life expectancy highlights the difficulties associated with discussing this sensitive topic. To ensure that life expectancy discussions correspond with patient preferences, clinicians should routinely ask patients whether they want to know this information, in what format, and at which level of detail.
Sirolimus Use in Liver Transplant Recipients With Hepatocellular Carcinoma: A Randomized, Multicenter, Open-Label Phase 3 Trial.
Transplantation. 2016; 100(1):116-25 [PubMed] Article available free on PMC after 01/02/2017 Related Publications
METHODS: In a prospective-randomized open-label international trial, 525 LTx recipients with HCC initially receiving mammalian target of rapamycin inhibitor-free immunosuppression were randomized 4 to 6 weeks after transplantation into a group on mammalian target of rapamycin inhibitor-free immunosuppression (group A: 264 patients) or a group incorporating sirolimus (group B: 261). The primary endpoint was recurrence-free survival (RFS); intention-to-treat (ITT) analysis was conducted after 8 years. Overall survival (OS) was a secondary endpoint.
RESULTS: Recurrence-free survival was 64.5% in group A and 70.2% in group B at study end, this difference was not significant (P = 0.28; hazard ratio [HR], 0.84; 95% confidence interval [95% CI], 0.62; 1.15). In a planned analysis of RFS rates at yearly intervals, group B showed better outcomes 3 years after transplantation (HR, 0.7; 95% CI, 0.48-1.00). Similarly, OS (P = 0.21; HR, 0.81; 95% CI, 0.58-1.13) was not statistically better in group B at study end, but yearly analyses showed improvement out to 5 years (HR, 0.7; 95% CI, 0.49-1.00). Interestingly, subgroup (Milan Criteria-based) analyses revealed that low-risk, rather than high-risk, patients benefited most from sirolimus; furthermore, younger recipients (age ≤60) also benefited, as well sirolimus monotherapy patients. Serious adverse event numbers were alike in groups A (860) and B (874).
CONCLUSIONS: Sirolimus in LTx recipients with HCC does not improve long-term RFS beyond 5 years. However, a RFS and OS benefit is evident in the first 3 to 5 years, especially in low-risk patients. This trial provides the first high-level evidence base for selecting immunosuppression in LTx recipients with HCC.
Cumulative Doses of T-Cell Depleting Antibody and Cancer Risk after Kidney Transplantation.
PLoS One. 2015; 10(11):e0139479 [PubMed] Article available free on PMC after 01/02/2017 Related Publications
Papillary Immature Metaplasia of the Anal Canal: A Low-grade Lesion That Can Mimic a High-grade Lesion.
Am J Surg Pathol. 2016; 40(3):348-53 [PubMed] Related Publications
Addressing unresolved tensions to build effective partnerships: lessons from an Aboriginal cancer support network.
Int J Equity Health. 2015; 14:122 [PubMed] Article available free on PMC after 01/02/2017 Related Publications
METHODS: Data were collected through semi-structured interviews with 24 participants purposively selected among Indigenous and mainstream healthcare service providers, and group members and clients. Interviews were audiotaped and transcribed verbatim. Transcripts were subjected to inductive thematic analysis. NVivo was used to manage the data and assist in the data analysis. Rigour was enhanced through team member checking, coding validation and peer debriefing.
RESULTS: Flexibility and a resistance to formal structuring were at the core of how the group operated. It was acknowledged that the network partly owned its success to its fluid approach; however, most mainstream healthcare service providers believed that a more structured approach was needed for the group to be sustainable. This was seen as acting in opposition to the flexible, organic approach considered necessary to adequately respond to Indigenous women's needs. At the core of these tensions were opposing perspectives on the constructs of 'structure' and 'flexibility' between Indigenous and non-Indigenous participants.
CONCLUSIONS: Despite the group's achievements, unresolved tensions between opposing perspectives on how a support group should operate negatively impacted on the working relationship between the group and mainstream service providers, and posed a threat to the Network's sustainability. Our results support the need to acknowledge and address different perspectives and world views in order to build strong, effective partnerships between service providers and Indigenous communities.
Vitamin D receptor polymorphisms and survival in patients with cutaneous melanoma: a population-based study.
Carcinogenesis. 2016; 37(1):30-8 [PubMed] Article available free on PMC after 01/01/2017 Related Publications