Nicholas Zdenkowski

Administration of chemotherapy with palliative intent in the last 30 days of life: The balance between palliation and chemotherapy

Appropriately timed cessation of chemotherapy is an important aspect of good quality palliative care. There is wide variation in the reported rates of chemotherapy administration within the last 30 days of life.

A systematic review of decision aids for patients making a decision about treatment for early breast cancer.

Several complex treatment decisions may be offered to women with early stage breast cancer, about a range of treatments from different modalities including surgery, radiotherapy, and endocrine and chemotherapy. Decision aids can facilitate shared decision-making and improve decision-related outcomes. We aimed to systematically identify, describe and appraise the literature on treatment decision aids for women with early breast cancer, synthesise the data and identify breast cancer decisions that lack a decision aid. A prospectively developed search strategy was applied to MEDLINE, the Cochrane databases, EMBASE, PsycINFO, Web of Science and abstract databases from major conferences. Data were extracted into a pre-piloted form. Quality and risk of bias were measured using Qualsyst criteria. Results were synthesised into narrative format. Thirty-three eligible articles were identified, evaluating 23 individual treatment decision aids, comprising 13 randomised controlled trial reports, seven non-randomised comparative studies, eight single-arm pre-post studies and five cross-sectional studies. The decisions addressed by these decision aids were: breast conserving surgery versus mastectomy (+/- reconstruction); use of chemotherapy and/or endocrine therapy; radiotherapy; and fertility preservation. Outcome measures were heterogeneous, precluding meta-analysis. Decisional conflict decreased, and knowledge and satisfaction increased, without any change in anxiety or depression, in most studies. No studies were identified that evaluated decision aids for neoadjuvant systemic therapy, or contralateral prophylactic mastectomy. Decision aids are available and improved decision-related outcomes for many breast cancer treatment decisions including surgery, radiotherapy, and endocrine and chemotherapy. Decision aids for neoadjuvant systemic therapy and contralateral prophylactic mastectomy could not be found, and may be warranted.

Curative Strategies for Liver Metastases from Colorectal Cancer: A Review

Colorectal cancer is a very common malignancy and frequently manifests with liver metastases, often without other systemic disease. Margin-negative (R0) resection of limited metastatic disease, in conjunction with systemic antineoplastic agents, is the primary treatment strategy, leading to long survival times for appropriately selected patients. There is debate over whether the primary tumor and secondaries should be removed at the same time or in a staged manner. Chemotherapy is effective in converting some unresectable liver metastases into resectable disease, with a correspondingly better survival outcome. However, the ideal chemotherapy with or without biological agents and when it should be administered in the course of treatment are uncertain. The role of neoadjuvant chemotherapy in initially resectable liver metastases is controversial. Local delivery of chemotherapy, with and without surgery, can lead to longer disease-free survival times, but it is not routinely used with curative intent. This review focuses on methods to maximize the disease-free survival interval using chemotherapy, surgery, and local methods.

Systemic treatment of HER2-positive metastatic breast cancer: A systematic review

We aimed to systematically review and summarize data from the available clinical trials that examined the treatment of HER2‐positive metastatic breast cancer.

Supportive care of women with breast cancer: key concerns and practical solutions.

Patients diagnosed with breast cancer may have supportive care needs for many years after diagnosis. High quality multidisciplinary care can help address these needs and reduce the physical and psychological effects of breast cancer and its treatment. Ovarian suppression and extended endocrine therapy benefits are associated with vasomotor, musculoskeletal, sexual and bone density‐related side effects. Aromatase inhibitor musculoskeletal syndrome is a common reason for treatment discontinuation. Treatment strategies include education, exercise, simple analgesia and a change to tamoxifen or another aromatase inhibitor. Chemotherapy‐induced alopecia may be a constant reminder of breast cancer to the patient, family, friends, acquaintances and even strangers. Alopecia can be prevented in some patients using scalp‐cooling technology applied at the time of chemotherapy infusion. The adverse impact of breast cancer diagnosis and treatment on sexual wellbeing is under‐reported. Identification of physical and psychological impacts is needed for implementation of treatment strategies. Fear of cancer recurrence reduces quality of life and increases distress, with subsequent impact on role functioning. Identification and multidisciplinary management are key, with referral to psychosocial services recommended where indicated. The benefits of exercise include reduced fatigue, better mental health and reduced musculoskeletal symptoms, and may also include reduced incidence of breast cancer recurrence. Identification and management of unmet supportive care needs are key aspects of breast cancer care, to maximise quality of life and minimise breast cancer recurrence.

Observation versus late reintroduction of letrozole as adjuvant endocrine therapy for hormone receptor-positive breast cancer (ANZ0501 LATER): an open-label randomised, controlled trial

BACKGROUND Despite the effectiveness of adjuvant endocrine therapy in preventing breast cancer recurrence, breast cancer events continue at a high rate for at least 10 years after completion of therapy. PATIENTS AND METHODS This randomised open label phase III trial recruited postmenopausal women from 29 Australian and New Zealand sites, with hormone receptor-positive early breast cancer, who had completed ≥4 years of endocrine therapy [aromatase inhibitor (AI), tamoxifen, ovarian suppression, or sequential combination] ≥1 year prior, to oral letrozole 2.5 mg daily for 5 years, or observation. Treatment allocation was by central computerised randomisation, stratified by institution, axillary node status and prior endocrine therapy. The primary outcome was invasive breast cancer events (new invasive primary, local, regional or distant recurrence, or contralateral breast cancer), analysed by intention to treat. The secondary outcomes were disease-free survival (DFS), overall survival, and safety. RESULTS Between 16 May 2007 and 14 March 2012, 181 patients were randomised to letrozole and 179 to observation (median age 64.3 years). Endocrine therapy was completed at a median of 2.6 years before randomisation, and 47.5% had tumours of >2 cm and/or node positive. At 3.9 years median follow-up (interquartile range 3.1-4.8), 2 patients assigned letrozole (1.1%) and 17 patients assigned observation (9.5%) had experienced an invasive breast cancer event (difference 8.4%, 95% confidence interval 3.8% to 13.0%, log-rank test P = 0.0004). Twenty-four patients (13.4%) in the observation and 14 (7.7%) in the letrozole arm experienced a DFS event (log-rank P = 0.067). Adverse events linked to oestrogen depletion, but not serious adverse events, were more common with letrozole. CONCLUSION These results should be considered exploratory, but lend weight to emerging data supporting longer duration endocrine therapy for hormone receptor-positive breast cancer, and offer insight into reintroduction of AI therapy. CLINICAL TRIALS NUMBER Australian New Zealand Clinical Trials Registry (www.anzctr.org.au), ACTRN12607000137493.

Exploring Decision‐Making about Neo‐adjuvant Chemotherapy for Breast Cancer

Neo-adjuvant chemotherapy (NACT) has become a routine treatment option that may be offered as a choice to women with large operable breast cancer, which may add to the burden of an already complex decision-making process. Published data are lacking on women’s involvement preferences in the decision about NACT, and what level of information complexity might reasonably be presented to a patient to achieve the benefits of shared decision-making (1). Here, we report on a study that aimed to understand women’s NACT decision-making process as the first step to better supporting women through this process, so that treatment can be matched with individuals’ personal values and preferences. We interviewed 22 women, identified via the Breast Cancer Network Australia Review and Survey Group, with a past diagnosis of invasive breast cancer, who had been offered either neo-adjuvant or adjuvant chemotherapy, and had completed surgery and chemotherapy. A semi-structured interview guide included questions about demographics; treatments and outcomes; information needs; decision-making preferences; and associated psychological issues. Responses were analyzed using qualitative descriptive methodology to identify overarching themes. Neo-adjuvant chemotherapy was offered to 19 women, accepted by 13 and declined by six. Three women had not been offered NACT. Participants’ age (median 51), metropolitan residential status and high levels of education employment health insurance imply high health literacy. All major breast cancer subtypes were represented, determined by self-report of hormone receptor and HER2 results. Two participants had taken part in a NACT clinical trial. Few women were aware of NACT before the option was raised by their surgeon. Women were not given, and were unable to find, written patient information specific to NACT. The Internet was seen as an unreliable information source, to the extent that many women avoided it. Women were aware of many information sources, but were reluctant to pursue them due to a fear of information overload and increased decisional conflict. In typical medical encounters, most women preferred to have sufficient information available to allow them to be the primary decision maker. However, the majority preferred to leave the decision about NACT to their doctor or, at most, take equal part in making the decision. Reasons included a perceived lack of time for decision-making and information gathering, the complexity of the multiple factors to be considered, and a sense of being overwhelmed by their breast cancer diagnosis. Women were very trusting of their treating clinicians to guide treatment decisions about NACT, which translated into a high level of decisional satisfaction. Trust in clinicians allows women to avoid the burden of decision-making when they are highly vulnerable, and places responsibility for the decision with the clinician. Hillen et al. suggest that women facing a life-threatening condition such as breast cancer have a ‘need for trust’, which underscores the power imbalance between cancer patients and their oncologist (2). Sensitive communication, clear information, and additional support may be needed to effectively share decision-making, if that is what patients prefer. Most women, with better information, would have preferred more control over the decision about NACT. Most women felt that having access to a decision support tool would have helped their decision-making. Patient decision aids have been shown to improve decision-related outcomes such as decisional conflict, patient involvement, knowledge, and satisfaction, without raising anxiety (3). Women with breast cancer who participate actively in decision-making have higher quality of life, physical, and social functioning, and less Address correspondence and reprint requests to: Dr Nicholas Zdenkowski, BMed, Australia and New Zealand Breast Cancer Trials Group, PO Box 155, HRMC, Newcastle, NSW 2310, Australia, or e-mail: nicholas.zdenkowski@anzbctg.org

Neoadjuvant chemotherapy with sequential anthracycline-docetaxel with gemcitabine for large operable or locally advanced breast cancer: ANZ 0502 (NeoGem)

BACKGROUND Neoadjuvant chemotherapy has a sound rationale for use in women with large operable breast cancer, and achievement of pathological complete response (pCR) is prognostic. Epirubicin and cyclophosphamide followed by docetaxel is a standard chemotherapy regimen for early breast cancer. In metastatic breast cancer the combination of gemcitabine and a taxane has shown promising results. This phase II study investigated the efficacy and safety of incorporating gemcitabine into neoadjuvant therapy. METHODS Female patients with operable breast cancer that was clinically T2 (≥3 cm) or T3-4, N0-1, M0 were enrolled to receive 24 weeks of neoadjuvant chemotherapy using epirubicin and cyclophosphamide followed by docetaxel and gemcitabine, plus trastuzumab if HER2-positive. The primary endpoint was the pathological complete response (pCR) rate in the breast in separate HER2-negative and HER2-positive cohorts. Secondary endpoints included pCR in both the breast and axillary lymph nodes, clinical and radiological response rates, disease free survival and safety. RESULTS 81 patients were enrolled: 63 HER2-negative and 18 HER2-positive. 67 (84%) completed all cycles of chemotherapy, and 78 (96%) proceeded to surgery. pCR was achieved by 12 (20%) patients with HER2-negative, and 9 (53%) with HER2-positive disease. At the first interim analysis, addition of prophylactic G-CSF was recommended due to excess neutropenia. The HER2-negative cohort was closed to accrual because it did not meet the pre-specified target for pCR, and the HER2-positive cohort was closed due to slow accrual. At a median follow-up of 24 months, 12 of 81 (15%) patients had experienced a relapse of their breast cancer. CONCLUSION Neoadjuvant gemcitabine, when added to docetaxel, after epirubicin and cyclophosphamide, did not reach the pre-specified expectations for pCR rate in HER2-negative tumours. Excess neutropenia was observed, requiring growth factor support. Addition of gemcitabine to docetaxel in this schedule cannot be recommended. Australia and New Zealand Clinical Trials Registry (www.anzctr.org.au) registration number ACTRN12606000191594.

The Right Place at the Right Time: Medical Oncology Outpatients' Perceptions of Location of End-of-Life Care

Background: Helping people achieve their preferred location of care is an important indicator of quality end-of-life (EOL) care. Using a sample of Australian medical oncology outpatients, this study examined (1) their preferred location of EOL care; (2) their perceived benefits and worries of receiving care in that location; (3) the percentage who had discussed preferences with their doctor and/or support person; and (4) whether they wanted their doctor to ask them where they wanted to die. Methods: Adults with a confirmed diagnosis of cancer were approached between September 2015 and January 2016 in the waiting room of an Australian oncology outpatient clinic. Consenting participants completed a home-based pen-and-paper survey indicating preferred location of care, perceived benefits and worries of that location, whether they had discussed preferences with their doctors, and whether they were willing to be asked about their preferences. Results: A total of 203 patients returned the survey (47% of those eligible). Less than half preferred to be cared for at home (47%), 34% preferred a hospice/palliative care unit, and 19% preferred the hospital. Common benefits and worries associated with locations included perceived burden on others, familiarity of environment, availability of expert medical care, symptom management, and likelihood of having wishes respected. More patients had discussed preferences with their support persons (41%) than doctors (7%). Most wanted a doctor to ask them about preferred location of care (87%) and thought it was important to die in the location of their choice (93%). Conclusions: Patients were willing to have clinicians to ask them where they wanted to die, although few had discussed their preferences with doctors. Although home was the most preferred location for many patients, the overall variation suggests that clinicians should adopt a systematic approach to eliciting patient preferences.

A Decision Aid for Women Considering Neoadjuvant Systemic Therapy for Operable Invasive Breast Cancer: Development and Protocol of a Phase II Evaluation Study (ANZ1301 DOMINO).

Background Neoadjuvant systemic therapy is offered to selected women with large and/or highly proliferative operable breast cancers. This option adds further complexity to an already complex breast cancer treatment decision tree. Patient decision aids are an established method of increasing patient involvement and knowledge while decreasing decisional conflict. There is currently no decision aid available for women considering neoadjuvant systemic therapy. Objective We aimed to develop a decision aid for women diagnosed with operable breast cancer and considered suitable for neoadjuvant systemic therapy, and the protocol for a multicenter pre-post study evaluating the acceptability and feasibility of the decision aid. Methods The decision aid was developed through literature review, expert advisory panel, adherence to the International Patient Decision Aid Standards, and iterative review. The protocol for evaluation of the decision aid consists of the following: eligible women will undertake a series of questionnaires prior to and after using the decision aid. The primary endpoint is decision aid acceptability to patients and investigators and the feasibility of use. Secondary endpoints include change in decisional conflict, participant knowledge, and information involvement preference. Feasibility is defined as the proportion of eligible participants who use the decision aid to help inform their treatment decision. Results This study has recruited 29 out of a planned 50 participants at four Australian sites. A 12-month recruitment period is expected with a further 12-months follow-up. Conclusions The decision aid has the potential to allow patients with operable breast cancer, who have been offered neoadjuvant systemic therapy, decreased decisional conflict, and greater involvement in the decision. If this study finds that an online decision aid is feasible and acceptable, it will be made widely available for routine clinical practice. Trial Registration Australian and New Zealand Clinical Trials Registry ACTRN12614001267640; http://www.anzctr.org.au/TrialSearch.aspx?searchTxt=ACTRN12614001267640&isBasic=True (Archived by WebCite at http://www.webcitation.org/6gh7BPZdG)