Stephen Della-Fiorentina

Bio: Stephen Della-Fiorentina is an academic researcher from Campbelltown Hospital. The author has contributed to research in topics: Breast cancer & Population. The author has an hindex of 8, co-authored 19 publications receiving 219 citations. Previous affiliations of Stephen Della-Fiorentina include Liverpool Hospital & University of New South Wales.

Extended adjuvant intermittent letrozole versus continuous letrozole in postmenopausal women with breast cancer (SOLE): a multicentre, open-label, randomised, phase 3 trial

Abstract: Summary Background In animal models of breast cancer, resistance to continuous use of letrozole can be reversed by withdrawal and reintroduction of letrozole. We therefore hypothesised that extended intermittent use of adjuvant letrozole would improve breast cancer outcome compared with continuous use of letrozole in postmenopausal women. Methods We did the multicentre, open-label, randomised, parallel, phase 3 SOLE trial in 240 centres (academic, primary, secondary, and tertiary care centres) in 22 countries. We enrolled postmenopausal women of any age with hormone receptor-positive, lymph node-positive, and operable breast cancer for which they had undergone local treatment (surgery with or without radiotherapy) and had completed 4–6 years of adjuvant endocrine therapy. They had to be clinically free of breast cancer at enrolment and without evidence of recurrent disease at any time before randomisation. We randomly assigned women (1:1) to treatment groups of either continuous use of letrozole (2·5 mg/day orally for 5 years) or intermittent use of letrozole (2·5 mg/day orally for 9 months followed by a 3-month break in years 1–4 and then 2·5 mg/day during all 12 months of year 5). Randomisation was done by principal investigators or designee at respective centres through the internet-based system of the International Breast Cancer Study Group, was stratified by type of previous endocrine therapy (aromatase inhibitors only vs selective oestrogen receptor modulators only vs both therapies), and used permuted block sizes of four and institutional balancing. No one was masked to treatment assignment. The primary endpoint was disease-free survival, analysed by the intention-to-treat principle using a stratified log-rank test. All patients in the intention-to-treat population who initiated protocol treatment during their period of trial participation were included in the safety analyses. This study is registered with ClinicalTrials.gov, number NCT00553410, and EudraCT, number 2007-001370-88; and long-term follow-up of patients is ongoing. Findings Between Dec 5, 2007, and Oct 8, 2012, 4884 women were enrolled and randomised after exclusion of patients at a non-adherent centre, found to have inadequate documentation of informed consent, immediately withdrew consent, or randomly assigned to intervention groups in error. 4851 women comprised the intention-to-treat population that compared extended intermittent letrozole use (n=2425) with continuous letrozole use (n=2426). After a median follow-up of 60 months (IQR 53–72), disease-free survival was 85·8% (95% CI 84·2–87·2) in the intermittent letrozole group compared with 87·5% (86·0–88·8) in the continuous letrozole group (hazard ratio 1·08, 95% CI 0·93–1·26; p=0·31). Adverse events were reported as expected and were similar between the two groups. The most common grade 3–5 adverse events were hypertension (584 [24%] of 2417 in the intermittent letrozole group vs 517 [21%] of 2411 in the continuous letrozole group) and arthralgia (136 [6%] vs 151 [6%]). 54 patients (24 [1%] in the intermittent letrozole group and 30 [1%] in the continuous letrozole group) had grade 3–5 CNS cerebrovascular ischaemia, 16 (nine [ vs seven [ vs 21 [1%]) had grade 3–5 cardiac ischaemia. In total, 23 ( vs ten [ Interpretation In postmenopausal women with hormone receptor-positive breast cancer, extended use of intermittent letrozole did not improve disease-free survival compared with continuous use of letrozole. An alternative schedule of extended adjuvant endocrine therapy with letrozole, including intermittent administration, might be feasible and the results of the SOLE trial support the safety of temporary treatment breaks in selected patients who might require them. Funding Novartis and the International Breast Cancer Study Group.

Development and feasibility testing of PROMPT-Care, an eHealth system for collection and use of patient-reported outcome measures for personalized treatment and care: a study protocol

Abstract: Background: Patient-reported outcome (PRO) measures have been used widely to screen for depression, anxiety, and symptoms in cancer patients. Computer-based applications that collect patients’ responses and transfer them to the treating health professional in real time have the potential to improve patient well-being and cancer outcomes. Objective: This study will test the feasibility and acceptability of a newly developed eHealth system which facilitates PRO data capture from cancer patients, data linkage and retrieval to support clinical decisions and patient self-management, and data retrieval to support ongoing evaluation and innovative research. Methods: The eHealth system is being developed in consultation with 3 overarching content-specific expert advisory groups convened for this project: the clinical advisory group, technical advisory group, and evaluation advisory group. The following work has already been completed during this phase of the study: the Patient-Reported Outcome Measures for Personalized Treatment and Care (PROMPT-Care) eHealth system was developed, patient-reported outcomes were selected (distress, symptoms, unmet needs), algorithms to inform intervention thresholds for clinical and self-management were determined, clinician PRO feedback summary and longitudinal reports were designed, and patient self-management resources were collated. PROsaiq, a custom information technology system, will transfer PRO data in real time into the hospital-based oncology information system to support clinical decision making. The PROMPT-Care system feasibility and acceptability will be assessed through patients completing PROMPT-Care assessments, participating in face-to-face cognitive interviews, and completing evaluation surveys and telephone interviews and oncology staff participating in telephone interviews. Results: Over the course of 3 months, the system will be pilot-tested with up to 50 patients receiving treatment or follow-up care and 6 oncology staff at 2 hospitals in New South Wales, Australia. Data will be collected to determine the accuracy and completeness of data transfer procedures, extent of missing data from participants’ assessments, acceptability of the eHealth system and usefulness of the self-management resources (via patient evaluation surveys and interviews), and acceptability and perceived usefulness of real-time PRO reporting (via oncology staff interviews) at the completion of the pilot phase. Conclusions: This research investigates implementation of evidence into real world clinical practice through development of an efficient and user-friendly eHealth system. This study of feasibility and acceptability of the newly developed eHealth system will inform the next stage of larger scale testing and future implementation of the system as part of routine care. ClinicalTrial: Australian New Zealand Clinical Trials Registry ACTRN1261500135294; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=369299i5(4):e227]

Shared Decision-making in the Medical Encounter: What Does It Mean? (Or, It Takes at Least Two to Tango)

Abstract: Shared decision-making is increasingly advocated as an ideal model of treatment decision-making in the medical encounter. To date, the concept has been rather poorly and loosely defined. This paper attempts to provide greater conceptual clarity about shared treatment decision-making, identify some key characteristics of this model, and discuss measurement issues. The particular decision-making context that we focus on is potentially life threatening illnesses, where there are important decisions to be made at key points in the disease process, and several treatment options exist with different possible outcomes and substantial uncertainty. We suggest as key characteristics of shared decision-making (1) that at least two participants-physician and patient be involved; (2) that both parties share information; (3) that both parties take steps to build a consensus about the preferred treatment; and (4) that an agreement is reached on the treatment to implement. Some challenges to measuring shared decision-making are discussed as well as potential benefits of a shared decision-making model for both physicians and patients.

Adjuvant Endocrine Therapy for Women With Hormone Receptor-Positive Breast Cancer: ASCO Clinical Practice Guideline Focused Update

Abstract: PurposeTo update the ASCO clinical practice guideline on adjuvant endocrine therapy based on emerging data about the optimal duration of aromatase inhibitor (AI) treatment.MethodsASCO conducted a s...

Immunotherapy for lung cancer

Abstract: Treatment of lung cancer remains a challenge, and lung cancer is still the leading cause of cancer-related mortality. Immunotherapy has previously failed in lung cancer but has recently emerged as a very effective new therapy, and there is now growing worldwide enthusiasm in cancer immunotherapy. We summarize why immune checkpoint blockade therapies have generated efficacious and durable responses in clinical trials and why this has reignited interest in this field. Cancer vaccines have also been explored in the past with marginal success. Identification of optimal candidate neoantigens may improve cancer vaccine efficacy and may pave the way to personalized immunotherapy, alone or in combination with other immunotherapy such as immune checkpoint blockade. Understanding the steps in immune recognition and eradication of cancer cells is vital to understanding why previous immunotherapies failed and how current therapies can be used optimally. We hold an optimistic view for the future prospect in lung cancer immunotherapy.

A Systematic Review of Strategies to Prevent Cisplatin‐Induced Nephrotoxicity

Abstract: Introduction Cisplatin, a platinum-based antineoplastic agent, is the cornerstone for the treatment of many malignancies. Nephrotoxicity is the primary dose-limiting toxicity, and various hydration regimens and supplementation strategies are used to prevent cisplatin-induced kidney injury. However, evidence-based recommendations on specific hydration regimens are limited. A systematic review was performed to evaluate clinical studies that have examined hydration and supplementation strategies to prevent cisplatin-induced nephrotoxicity. Materials and methods PubMed and Excerpta Medica databases were searched from 1966 through October 2015 for clinical trials and other studies focused on hydration regimens to prevent nephrotoxicity in cancer patients treated with cisplatin. The University of Oxford Centre for Evidence-Based Medicine criteria were used to grade level of evidence. Results Among the 1,407 identified studies, 24 were included in this systematic review. All studies differed on type, volume, and duration of hydration. Among the 24 studies, 5 evaluated short-duration hydration, 4 evaluated low-volume hydration, 4 investigated magnesium supplementation, and 7 reviewed forced diuresis with hydration. Short-duration and lower-volume hydration regimens are effective in preventing cisplatin-induced nephrotoxicity. Magnesium supplementation may have a role as a nephroprotectant, and forced diuresis may be appropriate in some patients receiving cisplatin. Conclusion Hydration is essential for all patients to prevent cisplatin-induced nephrotoxicity. Specifically, short-duration, low-volume, outpatient hydration with magnesium supplementation and mannitol forced diuresis (in select patients) represent best practice principles for the safe use of cisplatin. The Oncologist 2017;22:609-619 IMPLICATIONS FOR PRACTICE: The findings contained within this systematic review show that (a) hydration is essential for all patients to prevent cisplatin-induced nephrotoxicity, (b) short-duration, low-volume, outpatient hydration regimens appear to be safe and feasible, even in patients receiving intermediate- to high-dose cisplatin, (c) magnesium supplementation (8-16 milliequivalents) may limit cisplatin-induced nephrotoxicity, and (d) mannitol may be considered for high-dose cisplatin and/or patients with preexisting hypertension. These findings have broad implications for clinical practice and represent best practice principles for the prevention of cisplatin-induced nephrotoxicity.