A signal-seeking phase 2 study of Trastuzumab emtansine in tumours harbouring HER2 amplification or mutation.

This single-arm phase II non-randomised trial (ACTRN12619001265167) evaluated trastuzumab emtansine in solid cancers with HER2 amplification or mutation detected by comprehensive genomic profiling. The primary objective was objective response (OR), while secondary objectives included the time to progression (TTP) on study to TTP on prior therapy ratio, progression-free survival (PFS) and overall survival (OS). The cohort included 16 tumours with HER2 mutations (group 1) and 16 with HER2 amplification (group 2). After 17 months median follow-up, ORs occurred in 19% of group 1 (1 salivary gland carcinoma (SGC), 2 lung cancers) and 25% of group 2 (3 SGCs, 1 uterine carcinoma). Fourteen of 29 TTP-evaluable patients achieved a TTP ratio ≥1.3, including 10 without an OR. Median PFS and OS were 4.5 (95% CI 2.1-7.0) and 18.2 months (95% CI 8.1-not reached) respectively. Trastuzumab emtansine showed modest ORs and a favourable change in disease trajectory in select HER2-altered solid cancers.

Real-World Analysis of Breast Cancer Patients Qualifying for Adjuvant CDK4/6 Inhibitors.

BACKGROUND: Adjuvant CDK4/6 inhibitors abemaciclib and ribociclib improved disease-free survival (DFS) added to endocrine therapy in hormone receptor (HR)-positive HER2-negative early breast cancer (EBC), in monarchE (NCT03155997) and NATALEE (NCT03701334) trials respectively. We assessed the proportion and outcome of EBC patients qualifying for adjuvant CDK4/6 inhibitors in the real-world. METHODS: Consecutive female patients with HR-positive HER2-negative EBC between 1997 and 2017 from the Australian Capital Territory and South-East New South Wales Breast Cancer Treatment Group registry were analyzed. Patients eligible for abemaciclib had ≥4 axillary nodes involved or 1-3 nodes plus primary >5 cm or grade 3. Ribociclib eligibility was defined as node-positive and node-negative with primary >5 cm or >2 cm grade 3. RESULTS: Of 3840 patients, 671 (17.5%) were abemaciclib-eligible and 1587 (41.3%) ribociclib-eligible . The 5-year DFS was 77% and 94% in abemaciclib-eligible and noneligible registry patients respectively (HR 2.6, 95% CI 2.26-3.05, P < .001). The 5-year DFS was 86% and 97% in ribociclib-eligible and noneligible registry patients respectively (HR 1.92, 95% CI 1.67-2.19, P < .001). Compared with monarchE trial patients, abemaciclib-eligible registry patients were older (median 55 years in registry vs. 51 years in trial), with lower nodal burden (≥4 nodes in 44% in registry vs. 60% in trial). There were more stage III cancers in NATALEE trial patients (60%) than ribociclib-eligible registry patients (24%). CONCLUSIONS: Many women with EBC will qualify for adjuvant CDK4/6 inhibitors (17.5% abemaciclib, 41.3% ribociclib) with resource and workforce implications. In the real-world setting, a greater proportion of adjuvant CDK4/6-eligible patients have lower stage disease, therefore the absolute benefit from treatment may be smaller than estimated by the trials.

Beyond the main function: An experimental study of the use of hardwood boomerangs in retouching activities.

Retouched lithic tools result from the functional modification of their edges following knapping operations. The study of the later stages of the reduction sequence is fundamental to understanding the techno-functional features of any toolkit. In Australia, a gap exists in the study of the chaîne opératoire of lithic tools shaped or re-shaped through percussion retouching. In our previous works (Martellotta EF., 2021, Martellotta EF., 2022), we have presented evidence for the use of hardwood boomerangs for retouching purposes in Australian Aboriginal communities. Through a detailed experimental protocol, the present study demonstrates how boomerangs can function as retouchers. We found that the use-wear generated on the boomerang's surface during retouch activity is comparable to retouch-induced impact traces observed on Palaeolithic bone retouchers, as well as to experimental bone retouchers generated in our replication experiments. Finally, we explore the role that microscopic lithic chips embedded in the retouchers' surface play in the formation process of retouching marks. Our results address the need for a deeper investigation of percussion retouching techniques in Australian contexts, opening the possibility that uncommon objects-such as boomerangs-could be used for this task. This concept also highlights the broader topic of the highly diverse multipurpose application of many Indigenous tools throughout Australia. At the same time, the study reveals a deep functional connection between osseous and wooden objects-a topic rarely investigated in archaeological contexts.

Recurrence in early breast cancer: Analysis of data from 3,765 Australian women treated between 1997 and 2015.

BACKGROUND: Evidence suggests recent improvements in outcome in early breast cancer (EBC). AIM: To analyse recurrence in women with EBC from our region from 1997 to 2015. METHODS: We analysed recurrence in 3,765 women with EBC. Median follow up was 83·0 months. 62·5% had a symptomatic presentation. 81·8% were hormone receptor positive and 38·5% were node positive. Lymphovascular invasion (LVI) was present in 24·3%. Of the 2,686 women entered from 2002 onwards tested for HER2 status, 72·7% had a luminal tumour, 15·2% had a HER2+ tumour and 12·1% had a triple negative (TN) tumour. RESULTS: Recurrence occurred in 459 (12·2%), predominantly in distant sites (71·7%). In women entered from 2002 onwards, the five and 10 year recurrence rates were significantly lower in the luminal group than the HER2+ and the TN groups. Few recurrences occurred in HER2+ and TN cancers after 36 months. On multivariate analysis the following were associated with a significantly increased risk of recurrence: nodal involvement (p < 0·0001), tumour grade (p < 0·0001), symptomatic presentation (p < 0·0001), presence of LVI (p = 0·001), non-luminal tumour type (p < 0·0001) and tumour size >50 mm (p = 0·02). CONCLUSION: The recurrence rate in this series was much lower than in previous older series. Lymph node involvement, tumour grade, symptomatic presentation, presence of LVI, non-luminal tumour type and tumour size (>50 mm) were associated with an increased risk of recurrence. We strongly recommend that clinicians include the presence of LVI and symptomatic presentation as well as the other established tumour factors, when assessing the risk of recurrence in women with EBC.

The survival outcome of patients with metastatic colorectal cancer based on the site of metastases and the impact of molecular markers and site of primary cancer on metastatic pattern.

BACKGROUND: Pattern of spread in patients with metastatic colorectal cancer (mCRC) is variable and may reflect different biology in subsets of patients. This is a retrospective study to explore the outcome of patients with mCRC based on their site of metastasis at diagnosis and to explore the association between tumor characteristics [KRAS/RAS, BRAF, mismatch repair (MMR) status, site of primary] and the site of metastasis. METHODS: Patients from two Australian databases were divided into six groups based on site of metastasis at time of diagnosis of metastatic disease; lung-only, liver-only, lymph node-only or any patients with brain, bone or peritoneal metastases. Primary endpoint was overall survival (OS) of each cohort compared with the rest of the population. A Mantel-Haenszel chi-squared test used to explore the association between site of metastasis and selected tumor characteristics. RESULTS: Five thousand nine hundred and sixty-seven patients were included. In a univariate analysis, median OS was significantly higher when metastases were limited to lung or liver and shorter for those with brain, bone or peritoneal metastases (p < .001) in both datasets. BRAF mutation was strongly associated with peritoneal metastases (relative risk = 1.8, p < .001) with lower incidence of lung (RR = 0.3, p = .004) and liver (RR = 0.7, p = .005) limited metastases. Lung-only metastases were more frequent with KRAS/RAS mutation (RR = 1.4, p = .007). Left colon tumors were associated with bone (RR = 1.6, p < .001) and lung-only metastases (RR = 2.3, p = .001) while peritoneal spread was less frequent compared with right colon tumors (RR = 0.6, p < .001). Rectal cancer was associated with brain, bone and lung metastases (RR = 1.7; p = .002, 1.7; p < .001, 2.0; p < .001). Liver-only metastases were less frequent in deficient MMR tumors (RR = 0.7, p = .01). CONCLUSION: Survival duration with mCRC is related to the site of metastases with lung limited disease showing a more favorable survival outcome compared to other single metastatic site disease. The BRAF mutation and primary rectal cancer were associated with poor prognostic metastatic sites.

Does low volume high-intensity interval training elicit superior benefits to continuous low to moderate-intensity training in cancer survivors?

AIM: To determine the impact of low volume high-intensity interval training (LVHIIT) and continuous low to moderate-intensity exercise training (CLMIT) on cardiovascular disease (CVD) risk and health outcomes in cancer survivors. METHODS: Sedentary cancer survivors (n = 75, aged 51 ± 12 year) within 24 months of diagnosis, were randomised into three groups for 12 wk of LVHIIT (n = 25), CLMIT (n = 25) or control group (n = 25). The exercise intervention involved 36 sessions (three sessions per week). The LVHIIT group performed 7 x 30 s intervals (≥ 85% predicted maximal heart rate) with a 60 s rest between intervals, and the CLMIT group performed continuous aerobic training for 20 min (≤ 55% predicted maximal heart rate) on a stationary bike. Outcome variables were measured at baseline and at 12 weeks and analysed using a 3 x 2 (group x time) repeated measures ANCOVA to evaluate main and interaction effects. RESULTS: Significant improvements (time) were observed for seven of the 22 variables (ES 0.35-0.97, P ≤ 0.05). There was an interaction effect (P < 0.01) after 12 wk in the LVHIIT group for six-minute walk test (P < 0.01; d = 0.97; 95%CI: 0.36, 1.56; large), sit to stand test (P < 0.01; d = -0.83; 95%CI: -1.40, -0.22; large ) and waist circumference reduction (P = 0.01; d = -0.48; 95%CI: -1.10, 0.10; medium). An interaction effect (P < 0.01) was also observed for quality of life in both the LVHIIT (d = 1.11; 95%CI: 0.50, 1.72; large) and CLMIT (d = 0.57; 95%CI: -0.00, 1.20; moderate) compared with the control group (d = -0.15; 95%CI: -0.95, 0.65; trivial). CONCLUSION: Low-volume high-intensity training shows promise as an effective exercise prescription within the cancer population, showing greater improvements in cardio-respiratory fitness, lower body strength and waist circumference compared with traditional CLMIT and control groups. Both LVHIIT and CLMIT improved quality of life. A proposed benefit of LVHIIT is the short duration (3 min) of exercise required, which may entice more cancer survivors to participate in exercise, improving health outcomes and lowing the risk of CVD.

Intravesical Gemcitabine versus Intravesical Bacillus Calmette-Guérin for the Treatment of Non-Muscle Invasive Bladder Cancer: An Evaluation of Efficacy and Toxicity.

BACKGROUND: Intravesical Bacillus Calmette-Guérin (BCG) remains the standard adjuvant treatment for non-muscle invasive bladder cancer (NMIBC) following transurethral resection; however, BCG failure and related toxicities are common. OBJECTIVES: To compare the efficacy and toxicity of intravesical BCG and gemcitabine in the treatment of NMIBC. METHODS: Retrospective data were collected in the region of Canberra, Australia from January 2010 to December 2015. The survival cutoff was December 2016. Primary end point was disease-free survival (DFS) and secondary end point was toxicity. After optimal transurethral resection all patients received weekly intravesical BCG or gemcitabine for 6 weeks and maintenance treatment according to their risk. The recurrence was defined as histology proven tumor recurrence (any grade), or appearance of carcinoma in situ. RESULTS: One hundred and three patients were evaluable, 52 treated with BCG and 51 with gemcitabine with a median age of 77 and 78, and were mostly male. Approximately half of each received maintenance therapy. The groups were well balanced, apart from some difference in cancer risk groups. Twenty-one percent in the BCG group and 29% in the gemcitabine group had received prior BCG. Median follow up was 15.0 months. Median DFS was 19.6 months for BCG, whereas median DFS was not reached with gemcitabine. There was a trend toward improved DFS with gemcitabine in multivariate analysis, HR: 0.49 (95% CI: 0.22-1.06, p = 0.07). Adverse events were significantly less frequent with gemcitabine (7 versus 44%, p ≤ 0.05). There were four cases of systemic BCG infection. CONCLUSION: Intravesical gemcitabine was associated with a trend toward better DFS with significantly lower toxicity when compared with BCG. Intravesical BCG remains the standard first-line adjuvant therapy; however, intravesical gemcitabine could be a reasonable alternative in cases where BCG is contraindicated and for patients who are intolerant or refractory to BCG. A prospective phase 3 trial is needed to confirm the benefits of gemcitabine over BCG.

A pilot study examining the effects of low-volume high-intensity interval training and continuous low to moderate intensity training on quality of life, functional capacity and cardiovascular risk factors in cancer survivors.

PURPOSE: The aim of this study was to evaluate the effects of low-volume high-intensity interval training and continuous low to moderate intensity training on quality of life, functional capacity and cardiovascular disease risk factors in cancer survivors. METHODS: Cancer survivors within 24 months post-diagnosis were randomly assigned into the low-volume high-intensity interval training group (n = 8) or the continuous low to moderate intensity training group (n = 8) group for 36 sessions (12 weeks) of supervised exercise. The low-volume high-intensity interval training (LVHIIT) group performed 7 × 30 s intervals (≥85% maximal heart rate) and the continuous low to moderate intensity training (CLMIT) group performed continuous aerobic training for 20 min (≤55% maximal heart rate) on a stationary bike or treadmill. RESULTS: Significant improvements (time) were observed for 13 of the 23 dependent variables (ES 0.05-0.61, p ≤ 0.05). An interaction effect was observed for six minute walk test (18.53% [32.43-4.63] ES 0.50, p ≤ 0.01) with the LVHIIT group demonstrating greater improvements. CONCLUSION: These preliminary findings suggest that both interventions can induce improvements in quality of life, functional capacity and selected cardiovascular disease risk factors. The LVHIIT program was well tolerated by the participants and our results suggest that LVHIIT is the preferred modality to improve fitness (6MWT); it remains to be seen which intervention elicits the most clinically relevant outcomes for patients. A larger sample size with a control group is required to confirm the significance of these findings.

Administration of chemotherapy in patients on dialysis.

The prevalence of patients on dialysis has increased and these patients present a challenge for chemotherapy administration when diagnosed with cancer. A consensus on the dosage and timing of different chemotherapeutic agents in relation to dialysis has not been established. We describe the pattern of care and treatment outcome for cancer patients on dialysis in our institution. The dataset from the Australia and New Zealand Dialysis and Transplant Registry of patients on dialysis who had a diagnosis of cancer was obtained and matched to the pharmacy records in our institution to identify patients who had received chemotherapy while on dialysis. Relevant clinical information including details of the dialysis regimen, chemotherapy administration and adverse events was extracted for analysis. Between July 1999 and July 2014, 21 patients on dialysis were included for analysis. Five (23.8%) received chemotherapy, most of which was administered before dialysis sessions. As a result of adverse events, one patient discontinued treatment; two other patients required dose reduction or treatment delay. Chemotherapy administration was feasible in cancer patients on dialysis, but chemotherapy usage was low. Better understanding of the altered pharmacokinetics in patients on dialysis may improve chemotherapy access and practice.

Phase II, open-label trial of lapatinib and vinorelbine in women with previously treated HER2-positive metastatic breast cancer.

AIM: To evaluate the efficacy and tolerability of lapatinib (L) and intravenous vinorelbine (V) in patients with metastatic HER2-positive breast cancer who have previously received two lines of anti-HER2 therapy (i.e. trastuzumab [T] with chemotherapy and lapatinib with capecitabine [LC]). METHOD: Consenting patients with measurable or evaluable disease and normal cardiac function who had progressed were recruited. Patients received LV (lapatinib 1250 mg orally daily, vinorelbine 20 mg/m(2) intravenously on days 1 and 8 every 3 weeks) until progressive disease, intolerable toxicity or patient request. RESULTS: The trial was closed early following inclusion of 19 patients due to slow accrual. Ten, five and four patients had received two, three and more than four lines of chemotherapy with T and LC, respectively, prior to study entry. Patients received a median of 5 cycles (range 1-18) of LV. Confirmed partial response was seen in 2 of 16 patients with measurable disease (12.5%); stable disease >24 weeks was seen in two patients (10.5%) with a clinical benefit rate of 20%. Fatigue and any grade neutropenia occurred commonly, but grade 4 severity occurred in only 5 and 11%, respectively. There were no episodes of cardiac dysfunction and no treatment-related deaths. The median progression-free survival was 3.9 months and overall survival (OS) was 9.1 months. CONCLUSION: The combination of LV demonstrated modest efficacy but was well tolerated. This combination may be of benefit to those patients who are unable to access the newer anti-HER2 agents and the low rate of treatment-emergent adverse effects will enable patients' symptoms, such as pain, to be minimized.

Phase III, randomized, double-blind, placebo-controlled study of modafinil for fatigue in patients treated with docetaxel-based chemotherapy.

PURPOSE: Modafinil has been reported to benefit a subgroup of patients suffering severe fatigue while undergoing chemotherapy. Docetaxel is associated with fatigue that may lead to premature therapy withdrawal. We investigated whether modafinil could reduce fatigue during docetaxel chemotherapy. METHODS: This multicenter, randomized, double-blind, placebo-controlled study evaluated the efficacy of modafinil in patients with metastatic prostate or breast cancer undergoing docetaxel chemotherapy (every 21 days; minimum dose 50 mg/m(2)). At the start of their third or subsequent chemotherapy cycle, patients with significant docetaxel-associated fatigue were randomized to receive concurrent modafinil 200 mg/day or placebo for 15 days ("treatment periods" (TP)). Docetaxel was continued for up to four further cycles. Fatigue was evaluated with the fatigue component of the MD Anderson Symptom Inventory (MDASI). The primary endpoint was cumulative MDASI area under the curve (AUC) during the first 7 days of study medication during TP1 and TP2. RESULTS: Evaluable data were available from 83 patients (65 with prostate cancer). There was no statistically significant difference between the two treatment arms for the primary endpoint (MSADI AUC3-10 35.9 vs 39.6; 95 % confidence interval -8.9, 1.4; P=0.15). Overall toxicity was comparable between treatment groups; however, the incidence of grade ≤ 2 nausea and vomiting was higher in the modafinil arm (45.4 vs 25 %). CONCLUSIONS: Assessing and managing chemotherapy-related fatigue remains a major challenge. There was a lack of difference between the two arms in the planned primary endpoint. However, there was a modest but consistent trend towards improvement of docetaxel-related fatigue in those treated with modafinil. Based on the study findings, modafinil for the treatment of fatigue associated with docetaxel chemotherapy elicits modest improvements. Larger, longer term, randomized, controlled studies are required to clarify the exact role of modafinil in the treatment of docetaxel-related fatigue.

Surgical margins and risk of locoregional recurrence in invasive breast cancer: an analysis of 10-year data from the Breast Cancer Treatment Quality Assurance Project.

AIM: There is debate as to what constitutes an adequate excision margin to reduce the risk of locoregional recurrence (LRR) after breast cancer surgery. We have investigated the relationship between surgical margin distance and LRR in women with invasive breast cancer (IBC). METHODS: Tumour free margin distances were extracted from histopathology reports for women with IBC, treated by either breast conserving surgery or mastectomy, enrolled in the Breast Cancer Treatment Group Quality Assurance Project from July 1997 to June 2007. Cox proportional hazards regression analyses were conducted to compare the risk of LRR for involved margins compared with negative margins, measured in increments rounded to the nearest mm. RESULTS: 88 of 2300 patients (3.8%) experienced an LRR after a mean follow-up of 7.9 years. An involved margin, or a margin of 1 mm was associated with an increased risk of LRR (HR 2.72, 95% CI 1.30-5.69), whilst margin distances of 2 mm or greater were not. Risk of LRR with margin distances <2 mm was particularly high amongst those not receiving radiotherapy (RT). CONCLUSION: Based on our findings, we recommend that a tumour free margin distance of 2 mm be adopted as an adequate margin of excision for IBC, in the setting of patients receiving standard adjuvant RT and adjuvant drug therapies as dictated by the current clinical treatment paradigms.

Comparison of two standard chemotherapy regimens for good-prognosis germ cell tumors: updated analysis of a randomized trial.

BACKGROUND: The Australian and New Zealand Germ Cell Trials Group conducted a multicenter randomized phase III trial in men with good-prognosis germ cell tumors of two standard chemotherapy regimens that contained bleomycin, etoposide, and cisplatin but differed in the scheduling and total dose of cisplatin, the total dose of bleomycin, and the scheduling and dose intensity of etoposide. The trial was stopped early at a median follow-up of 33 months after a planned interim analysis found a survival benefit for the more dose-intense regimen. The aim of this analysis was to determine if this survival benefit was maintained with long-term follow-up. METHODS: Between February 1994 and April 2000, 166 men with good-prognosis metastatic germ cell tumors defined by modified Memorial Sloan-Kettering criteria were randomly assigned to receive 3B(90)E(500)P (three cycles, repeated every 21 days, of 30 kU bleomycin on days 1, 8, and 15; 100 mg/m(2) etoposide on days 1-5; and 20 mg/m(2) cisplatin on days 1-5; n = 83) or 4B(30)E(360)P (four cycles, repeated every 21 days, of 30 kU bleomycin on day 1, 120 mg/m(2) etoposide on days 1-3, and 100 mg/m(2) cisplatin on day 1; n = 83). Endpoints included overall survival, progression-free survival, and quality of life and side effects, which were assessed using the Spitzer Quality of Life Index and the GLQ-8, respectively, before random assignment and during and after treatment. All analyses were by intention to treat. All P values are two-sided. RESULTS: The median follow-up was 8.5 years. All but five survivors (3%) were followed up for at least 5 years. Overall survival remained better in those assigned to 3B(90)E(500)P than in those assigned to 4B(30)E(360)P (8-year survival: 92% vs 83%; hazard ratio of death = 0.38, 95% confidence interval = 0.15 to 0.97, P = .037). Progression-free survival favored 3B(90)E(500)P but was not statistically significantly different between the treatment groups (8-year progression-free survival, 3B(90)E(500)P vs 4B(30)E(360)P: 86% vs 79%; hazard ratio of progression = 0.6, 95% confidence interval = 0.3 to 1.1, P = .15). At the end of treatment, average scores for most side effect scales favored 3B(90)E(500)P. After the completion of treatment, average GLQ-8 scores for numbness (P = .003) and hair loss (P = .04) and the Spitzer Quality of Life Index (P = .05) favored 3B(90)E(500)P. CONCLUSION: The survival benefit of 3B(90)E(500)P over 4B(30)E(360)P was maintained with long-term follow-up.

Variation in the management of early breast cancer in rural and metropolitan centres: implications for the organisation of rural cancer services.

The study examines the management and outcomes of women with early invasive breast cancer treated in rural and metropolitan centres over a nine-year observation period. A prospective audit of the treatment and outcomes of 2081 women with early breast cancer who underwent potentially curative surgery between 1997 and 2006 in metropolitan Canberra or in the surrounding rural region was completed. Overall, there was good agreement between published guidelines and the treatment received by the women in the study. However, women treated in rural centres were less likely to receive postoperative radiotherapy after breast-conserving surgery, or to undergo axillary lymph node surgery or sentinel lymph node biopsy compared with women treated in metropolitan centres. Surgery in a rural centre was associated with increased breast cancer recurrence (HR = 1.54, p < 0.001) and increased breast cancer mortality (HR = 1.84, p < 0.001), after adjustment for age and tumour characteristics. Non-cancer related mortality was increased in women treated in rural centres compared with women travelling to a metropolitan centre for surgery (HR = 2.08; p = 0.005). There were differences in both the care provided and treatment outcomes between women treated in rural centres and women treated in metropolitan centres. However, the increased non-cancer related mortality in women treated in rural centres suggests an increased medical comorbidity in this group. Initiatives supporting rural-based surgeons to adopt new procedures such as sentinel node biopsy may help to optimise rural breast cancer treatment.

Cost and cost-effectiveness of digital mammography compared with film-screen mammography in Australia.

OBJECTIVE: A systematic review assessed the relative safety and effectiveness of digital mammography compared with film-screen mammography. This study utilised the evidence from the review to examine the economic value of digital compared with film-screen mammography in Australia. METHODS: A cost-comparison analysis between the two technologies was conducted for the overall population for the purposes of breast cancer screening and diagnosis. In addition, a cost-effectiveness analysis was conducted for the screening subgroups where digital mammography was considered to be more accurate than film-screen mammography. RESULTS: Digital mammography in a screening setting is $11 more per examination than film-screen mammography, and $36 or $33 more per examination in a diagnostic setting when either digital radiography or computed radiography is used. In both the screening and diagnostic settings, the throughput of the mammography system had the most significant impact on decreasing the incremental cost/examination/year of digital mammography. CONCLUSION: Digital mammography is more expensive than film-screen mammography. Whether digital mammography represents good value for money depends on the eventual life-years and quality-adjusted life-years gained from the early cancer diagnosis. IMPLICATIONS: The evidence generated from this study has informed the allocation of public resources for the screening and diagnosis of breast cancer in Australia.

Fluctuating awareness of treatment goals among patients and their caregivers: a longitudinal study of a dynamic process.

BACKGROUND: Because increasing numbers of people now survive for months or years with advanced cancer, communication between patients, service providers, and family caregivers often continues over long periods. Hence, understanding of the goals of medical treatment may develop and change as time elapses and disease progresses. This understanding is closely related to the "awareness of dying," which has been studied in both qualitative and quantitative research. However, when both a patient and family caregiver are involved, the question of "awareness" becomes more complex. A recent longitudinal study reported on patient and caregiver knowledge of treatment goals, but no comparison of such knowledge using matched interview schedules and paired data analysis has been provided. This report examines patterns of awareness and factors associated with these patterns. MATERIALS AND METHODS: One hundred sixty-three patients with incurable cancer and their nominated principal family caregivers (136) were recruited from The Canberra Hospital Oncology Services. Participants' understanding of the treatment goals were measured by interview questions at weeks 1 and 12. RESULTS: One-third of both patients and caregivers understood that the treatment goal was not curative; however, not all patient and caregiver pairs had the same understanding. In 15% of pairs, both patient and caregiver believed that the goal of treatment was curative, while another 13% said that they did not know the aim of the treatment. Thirty-nine percent of pairs registered incongruent responses in which only one member of the pair understood that the treatment was not intended to cure the disease. Over time, a few respondents changed their perception of the treatment goals toward accurate clarification. Bivariate analysis using an awareness variable, constructed for the purpose, showed that in 6 months before death, at least one person in 89% of pairs understood that the treatment was noncurative. Time-to-death, gender, and place of residence were also important predictors of knowledge. CONCLUSIONS: Discrepancies between patients and their caregivers may complicate the delivery of effective care when patients are seriously ill. Misunderstanding or uncertainty about treatment goals will obstruct proper informed consent. Health professionals providing care for families dealing with advanced cancer must recognize that the discussion of treatment goals is a dynamic process, which may require them to extend their communication skills.

Surgical management of invasive breast cancer: a 5-year prospective study of treatment in the Australian Capital Territory and South-Eastern New South Wales.

BACKGROUND: Breast cancer is a major health problem in Australia. The aim of the present report is to evaluate the surgical management of invasive breast cancers in our region. METHODOLOGY: As part of a multidisciplinary quality assurance project, data were collected for the majority of breast cancers treated in our region between July 1997 and June 2002. Participants included surgeons, medical and radiation oncologists, pathologists and general practitioners. RESULTS: Over the 5-year period, 1069 invasive breast cancers were treated. Mastectomy (52%) was more common than breast conservation. For cancers less than 2 cm in diameter (61%), breast conservation was achieved in 62%. High nuclear grade cancers (27%) resulted in mastectomy in 60%. This treatment pattern was the same for patients living in urban and rural areas and in all age groups. Those patients requiring two or more operations (30%) to achieve surgical clearance still had a 33% rate of breast conservation. Over the last 5 years there has been an increase in sentinel node biopsies (16 sentinel node biopsies during 1998-1999; 64 during 2001-2002) and axillary dissections started to decrease. A small group has had no axillary node biopsy or dissection, mainly patients over 70 years of age. Multimodality treatments increased over the 5-year period of our study with the use of postoperative radiotherapy increasing from 60% to 65% and chemotherapy from 36% to 55%. CONCLUSIONS: The project has mapped treatment trends for breast cancer in our region and documented the implementation of new treatment methods as well as the increasing use of multidisciplinary management, multimodality treatment and the implementation of best practice guidelines.

Does emotional support influence survival? Findings from a longitudinal study of patients with advanced cancer.

A total of 163 patients with advanced cancer at an Australian teaching hospital were interviewed to investigate whether emotional support was predictive of survival duration. Survival was analysed using the Kaplan-Meier product-limit estimate, and multivariable Cox proportional hazards regression, from entry to the study in 1996 to date of death, or 31 March 2003, whichever came first. The number of confidants with whom feelings were being shared at the time of study entry was predictive of survival duration. The regression analysis indicated that compared with patients reporting two or three confidants, the relative risk of a shorter survival (95% confidence limits) was 0.44 (0.25, 0.79) for those with no or one confidant and 0.60 (0.40, 0.89) for those with four or more confidants. Shorter survivors shared their feelings more with family members than longer survivors. Conversely, longer survivors shared their feelings more with friends than shorter survivors. These relationships did not hold at 12 weeks from study entry. At that time, longer survivors were more likely to be sharing their feelings with a doctor than shorter survivors. The relationship between emotional support and survival duration was not linear and appeared to be more complex than reported previously for people with heart disease and newly diagnosed breast cancer.