Correlation between initial tumour volume and treatment duration on Dabrafenib: observation study of subjects with BRAF mutant melanoma on the BRF112680 trial.

BACKGROUND: Planar-based measurements of lesions in metastatic melanoma have limitations in estimating tumor burden of a patient and in predicting response to treatment. Volumetric imaging might add predictive value to Response criteria in Solid Tumor (RECIST)-measurement. Based on clinical observations, we explored the association between baseline tumor volume (TV) and duration of treatment with dabrafenib in patients with metastatic melanoma. We have also explored the prognostic value of TV for overall survival (OS) and progression free survival (PFS). METHODS: This is a retrospective, chart-review of primary source documents and medical imaging of a cohort of patients participating in the BRF112680 phase 1 clinical trial at the Prince of Wales Hospital. TV was quantified by contouring all the measurable baseline target lesions in the standard manner for radiation planning using Voxxar™ software. We used Cox regression models to analyse associations between TV and duration of treatment with dabrafenib and between TV, PFS and OS. RESULTS: Among 13 patients of BRAF 112680 trial, 10 were included in the retrospective analysis. Target lesion sum volume ranged from 0.3 to 1065.5 cm3 (cc), with a median of 27.5 cc. The median PFS and OS were 420 days (range 109-1765) and 1680 days (range 390-2940), respectively. The initial TV was inversely correlated with duration of treatment with dabrafenib (rho - 0.6; P 0.03). In multivariate analysis, TV was a predictor for OS (HR 2.81 CI 1.06-6.19) and PFS (8.76 (CI 1.05-43.58). Patients with tumour volume above the median had significantly lower OS of 6-months compared to 56-months survival for patients with smaller volumes; P = 0.019. CONCLUSIONS: TV is a predictor for treatment duration and is prognostic of OS and PFS in patients with metastatic melanoma. These findings need to be validated prospectively in clinical trials.

Assessing suitability for long-term colorectal cancer shared care: a scenario-based qualitative study.

BACKGROUND: Shared care is the preferred model for long-term survivorship care by cancer survivors, general practitioners and specialists. However, survivorship care remains specialist-led. A risk-stratified approach has been proposed to select suitable patients for long-term shared care after survivors have completed adjuvant cancer treatment. This study aims to use patient scenarios to explore views on patient suitability for long-term colorectal cancer shared care across the risk spectrum from survivors, general practitioners and specialists. METHODS: Participants completed a brief questionnaire assessing demographics and clinical issues before a semi-structured in-depth interview. The interviews focused on the participant's view on suitability for long term cancer shared care, challenges and facilitators in delivering it and resources that would be helpful. We conducted thematic analysis using an inductive approach to discover new concepts and themes. RESULTS: Interviews were conducted with 10 cancer survivors, 6 general practitioners and 9 cancer specialists. The main themes that emerged were patient-centredness, team resilience underlined by mutual trust and stronger system supports by way of cancer-specific training, survivorship care protocols, shared information systems, care coordination and navigational supports. CONCLUSIONS: Decisions on the appropriateness of this model for patients need to be made collaboratively with cancer survivors, considering their trust and relationship with their general practitioners and the support they need. Further research on improving mutual trust and operationalising support systems would assist in the integration of shared survivorship care.

Patient, general practitioner and oncologist views regarding long-term cancer shared care.

Background: The rising incidence of cancer and increasing number of cancer survivors place competing demands on specialist oncology clinics. This has led to a need to consider collaborative care between primary and secondary care for the long-term post-treatment care of cancer survivors. Objective: To explore the views of breast and colorectal cancer survivors, their oncologist and GP about GPs taking a more active role in long-term cancer follow-up care. Methods: Semi-structured interviews using a thematic analysis framework. Respondents were asked their views on the specialist hospital-based model for cancer follow-up care and their views on their GP taking a greater or leading role in follow-up care. Researcher triangulation was used to refine the coding framework and emergent themes; source triangulation and participant validation were used to increase credibility. Results: Fifty-six interviews were conducted (22 patients, 16 oncologists, 18 GPs). Respondents highlighted the importance of GPs needing specialist cancer knowledge; the need for GPs to have an interest in and time for cancer follow-up care; the GPs role in providing psychosocial care; and the reassurance that was provided from a specialist overseeing care. A staged, shared care team arrangement with both GPs and specialists flexibly providing continuing care was found to be acceptable for most. Conclusion: Collaborative care of cancer survivors may lessen the load on specialist oncology clinics. The findings suggest that building this model will require early and ongoing shared care processes.

Using behaviour change and implementation science to address low referral rates in oncology.

BACKGROUND: Patients undergoing surgery for bowel cancer now have a routine screening test to assess their genetic predisposition to this and other cancers (Lynch syndrome). A result indicating a high risk should trigger referral to a genetic clinic for diagnostic testing, information, and management. Appropriate management of Lynch syndrome lowers morbidity and mortality from cancer for patients and their family, but referral rates are low. The aim of this project was to increase referral rates for patients at high risk of Lynch syndrome at two Australian hospitals, using the Theoretical Domains Framework (TDF) Implementation approach. METHODS: Multidisciplinary teams at each hospital mapped the referral process and discussed barriers to referral. A 12-month retrospective audit measured baseline referral rates. The validated Influences on Patient Safety Behaviours Questionnaire was administered to evaluate barriers using the TDF. Results were discussed in focus groups and interviews, and interventions co-designed, guided by theory. Continuous monitoring audits assessed change in referral rates. RESULTS: Teams (n = 8, 11) at each hospital mapped referral processes. Baseline referral rates were 80% (4/5) from 71 screened patients and 8% (1/14) from 113 patients respectively. The questionnaire response rate was 51% (36/71). Most significant barrier domains were: 'environmental context;' 'memory and decision making;' 'skills;' and 'beliefs about capabilities.' Focus groups and interviews with 19 healthcare professionals confirmed these domains as significant. Fifteen interventions were proposed considering both emerging and theory-based results. Interventions included: clarification of pathology reports, education, introduction of e-referrals, and inclusion of genetic status in documentation. Audits continued to December 2016 showing a change in pathology processes which increased the accuracy of screening. The referral rate remained low: 46% at Hospital A and 9% Hospital B. Results suggest patients who have their referral deferred for some reason are not referred later. CONCLUSION: Lynch syndrome is typical of low incidence problems likely to overwhelm the system as genomic testing becomes mainstream. It is crucial for health researchers to test methods and define generalizable solutions to address this problem. Whilst our approach did not improve referrals, we have deepened our understanding of barriers to referral and approaches to low frequency conditions.

Dexamethasone Modifies Cystatin C-Based Diagnosis of Acute Kidney Injury During Cisplatin-Based Chemotherapy.

BACKGROUND/AIMS: Plasma cystatin C (pCysC) may be superior to serum creatinine (sCr) as a surrogate of GFR. However, the performance of pCysC for diagnosing acute kidney injury (AKI) after cisplatin-based chemotherapy is potentially affected by accompanying corticosteroid anti-emetic therapy and hydration. METHODS: In a prospective observational study pCysC, sCr, urinary kidney injury molecule-1 (KIM-1), and urinary clusterin were measured over 2 weeks in 27 patients given first-cycle chemotherapy. The same variables were measured over 2 weeks in Sprague-Dawley rats given a single intraperitoneal injection of dexamethasone, cisplatin, or both, and in controls. RESULTS: In patients, pCysC increases were greater than sCr 41% vs. 16%, mean paired difference 25% (95% CI: 16-34%)], relative increases were ≥ 50% in 9 patients (35%) for pCysC compared with 2 (8%) for sCr (p = 0.04) and increases in sCr were accompanied by increased KIM-1 and clusterin excretion, but increases in pCysC alone were not. In rats, dexamethasone administration produced dose-dependent increases in pCysC (and augmented cisplatin-induced increases in pCysC), but did not augment histological injury, increases in sCr, or KIM-1 and clusterin excretion. CONCLUSIONS: In the presence of dexamethasone, elevation of pCysC does not reliably diagnose AKI after cisplatin-based chemotherapy.

The Impact of Mismatch Repair Status in Colorectal Cancer on the Decision to Treat With Adjuvant Chemotherapy: An Australian Population-Based Multicenter Study.

BACKGROUND: Testing for mismatch repair (MMR) status in colorectal cancer (CRC) may provide useful prognostic and predictive information. We evaluated the impact of such testing on real-world practice regarding adjuvant chemotherapy for patients with resected CRC. PATIENTS AND METHODS: A total of 175 patients with stage II and III mismatch repair-deficient (MMRD) CRC were identified from an Australian population-based study of incident CRCs. Their treatment decisions were compared with those for a cohort of 773 stage-matched patients with mismatch repair-proficient (MMRP) CRCs. The effect of MMR status, age, and pathologic characteristics on treatment decisions was determined using multiple regression analysis. RESULTS: Overall, 32% of patients in stage II and 71% of patients in stage III received adjuvant chemotherapy. Among the stage II patients, those with MMRD cancer were less likely to receive chemotherapy than were MMRP cases (15% vs. 38%; p < .0001). In this group, the treatment decision was influenced by age, tumor location, and T stage. MMR status influenced the treatment decision such that its impact diminished with increasing patient age. Among patients with stage III tumors, no difference was found in the chemotherapy rates between the MMRD and MMRP cases. In this group, age was the only significant predictor of the treatment decision. CONCLUSION: The findings of this study suggest that knowledge of the MMR status of sporadic CRC influences treatment decisions for stage II patients, in an era when clear recommendations as to how these findings should influence practice are lacking. IMPLICATIONS FOR PRACTICE: Microsatellite instability (MSI) is a molecular marker of defective DNA mismatch repair found in 15% of sporadic colorectal cancers. Until recently, expert guidelines on the role of MSI as a valid biomarker in the selection of stage II patients for adjuvant chemotherapy were lacking. Conducted at a time when the clinical utility of routine MSI testing was unclear, this study found that clinicians were influenced by MSI status in selecting stage II patients for chemotherapy. Furthermore, the impact of MSI on treatment decisions was greatest in younger patients and declined progressively until age 80 years, when no effect was found.

Achieving behaviour change for detection of Lynch syndrome using the Theoretical Domains Framework Implementation (TDFI) approach: a study protocol.

BACKGROUND: Lynch syndrome is an inherited disorder associated with a range of cancers, and found in 2-5 % of colorectal cancers. Lynch syndrome is diagnosed through a combination of significant family and clinical history and pathology. The definitive diagnostic germline test requires formal patient consent after genetic counselling. If diagnosed early, carriers of Lynch syndrome can undergo increased surveillance for cancers, which in turn can prevent late stage cancers, optimise treatment and decrease mortality for themselves and their relatives. However, over the past decade, international studies have reported that only a small proportion of individuals with suspected Lynch syndrome were referred for genetic consultation and possible genetic testing. The aim of this project is to use behaviour change theory and implementation science approaches to increase the number and speed of healthcare professional referrals of colorectal cancer patients with a high-likelihood risk of Lynch syndrome to appropriate genetic counselling services. METHODS: The six-step Theoretical Domains Framework Implementation (TDFI) approach will be used at two large, metropolitan hospitals treating colorectal cancer patients. Steps are: 1) form local multidisciplinary teams to map current referral processes; 2) identify target behaviours that may lead to increased referrals using discussion supported by a retrospective audit; 3) identify barriers to those behaviours using the validated Influences on Patient Safety Behaviours Questionnaire and TDFI guided focus groups; 4) co-design interventions to address barriers using focus groups; 5) co-implement interventions; and 6) evaluate intervention impact. Chi square analysis will be used to test the difference in the proportion of high-likelihood risk Lynch syndrome patients being referred for genetic testing before and after intervention implementation. A paired t-test will be used to assess the mean time from the pathology test results to referral for high-likelihood Lynch syndrome patients pre-post intervention. Run charts will be used to continuously monitor change in referrals over time, based on scheduled monthly audits. DISCUSSION: This project is based on a tested and refined implementation strategy (TDFI approach). Enhancing the process of identifying and referring people at high-likelihood risk of Lynch syndrome for genetic counselling will improve outcomes for patients and their relatives, and potentially save public money.

Sharing Colorectal Cancer Follow-Up Using an E-Care Plan Between Cancer Services and Primary Health Care.

High quality, long term follow-up care for cancer patients needs to be coordinated, comprehensive and tailored to the diverse needs of patients. This study implemented shared follow-up care using an interactive e-care plan that provided a collaborative space to schedule and share goals, tasks and information and support the monitoring of care. Qualitative results identified good relational coordination. Increasing communication from the cancer service is important.

Improving Medication Safety in Cancer Services for Ethnic Minority Consumers: Protocol for a Pilot Feasibility and Acceptability Study of a Co-Designed Consumer Engagement Intervention.

BACKGROUND: People from ethnic minorities are often exposed to unsafe care contributing to poorer health care outcomes. Medication safety is a high-risk area requiring intervention to improve care outcomes. Using an adapted, experience-based co-design process with cancer service staff and patients from ethnic minorities, a medication communication tool was created: Making it Meaningful (MiM). OBJECTIVE: We aim to test whether the MiM tool is feasible and acceptable for use with ethnic minority consumers in cancer services in Australia. METHODS: A single site, controlled before and after this pilot study, will be used. Patients from Mandarin- and Russian-speaking backgrounds are eligible for inclusion. In total, 40 patients from these cultural backgrounds will be recruited and stratified by language to the intervention and control groups, with 20 participants in the intervention and 20 in the control group. Further, 4 health practitioners will be recruited and trained to use the MiM. Clinicians providing care for patients in the intervention will use the MiM during their usual appointment while providing medication communication using standard care processes for the control group. Telephone surveys will be conducted with participants at 3 time points, T1 before the intervention, T2 1 week post intervention, and T3 1 month post intervention, to assess knowledge and self-efficacy in medication management, perceived usability, and acceptability of the MiM. Qualitative interviews with clinicians who have used the MiM will be conducted 1 month postintervention to explore their perceptions of MiM feasibility and acceptability. RESULTS: Ethical approval for this research has been provided by the South Eastern Sydney Area Health Human Research Ethics Committee (HRECXXX). Bilingual field-workers, 1 Mandarin-speaking and 1 Russian-speaking, are contacting eligible patients to enroll. It is anticipated that recruitment will be completed by October 2023, with data collection completed by December 2023. CONCLUSIONS: Using experience-based co-design, we identified communication about medication, particularly between appointments, as a key issue impacting the safety of care for patients from ethnic minorities accessing cancer services. Increasing consumer engagement in medication management was identified as a strategy to reduce medication safety problems in cancer care; the MiM strategy was developed to address this issue. It is anticipated that by using the MiM, patient knowledge about prescribed medications and confidence in medication management will increase. Evidence from the pilot study will be used to inform a full-scale trial of the MiM tool with a range of ethnic minority communities accessing cancer services. A full-scale trial will seek to determine whether the MiM intervention is effective in knowledge and confidence about medication management, but also whether this improves patient outcomes in cancer care. TRIAL REGISTRATION: Australian New Zealand Clinical Trials ACTRN12622001260718p; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=384658&isReview=true. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/49902.

What does co-design mean for Australia’s diverse clinical workforce?

Co-design is increasingly employed as a user-centric method to create healthcare change. In healthcare co-design, small groups of consumers and healthcare workers come together to identify processes, policies or service elements that require improvement and to design solutions. Multiple frameworks have emerged to guide the health work force and health researchers how to conduct co-design and support consumer members to engage in the process effectively. Frameworks have sought to address the propensity for co-design to exacerbate inequities for consumers with complex care needs or in under-served populations. Advice regarding the need to consider and ensure co-design is accessible to an increasingly diverse health workforce is, however, lacking. Drawing on our experience co-designing with diverse consumer and healthcare-worker populations, we discuss the implications of co-design for the healthcare workforce.

Challenges and solutions to sharing a cancer follow-up e-care plan between a cancer service and general practice.

OBJECTIVE: This paper describes the process of developing a shared cancer care approach in follow-up, and identifies the e-health options that support an interactive e-care plan shared between a public cancer service, general practitioners (GPs) and cancer survivors. Type of program/service: The cancer service improvement initiative for shared care in follow-up targets colorectal cancer patients who have completed active treatment and who agree to shared care between specialists, GPs and other care team members. The intiative is supported by an agreed shared care pathway and an interactive e-care plan that is dynamic, can be shared and has functionalities that support collaboration. Design and development: A consultative process with stakeholders (local and state health services, a Primary Health Network, GPs and a consumer) was undertaken. Responses from individual consultations (25 stakeholders) were collated and commonalities identified to inform a workshop with 13 stakeholders to obtain consensus on the care pathway and e-health solution. Implications for policy and practice were identified throughout the process. OUTCOMES: The stakeholders agreed to a shared care pathway, which included assessment and consent, GP engagement, tailoring the care plan and communicating results and information as tasks are completed. The nurse coordinator monitored care. No interactive e-care plans were available at national, state or local health service levels. A web-based GP interactive e-care plan was selected. The main concerns raised were uncertainty about the security of e-health systems not controlled by the local health service and sharing clinical information with external health providers, engaging GPs, and patient anxiety about the capacity of general practice to provide care. The e-care plan provided a low-risk solution to sharing patient information and supported collaborative care. Challenges to share e-care plans have implications for policy and practice. LESSONS LEARNT: Stakeholders and the project team agreed that finding an e-health system that supported shared cancer care in follow-up and addressed the security and information sharing concerns could not all be adequately addressed at the local level. A GP interactive e-care plan provides a promising solution to a number of the barriers.

Codesigning consumer engagement strategies with ethnic minority consumers in Australian cancer services: the CanEngage Project protocol.

INTRODUCTION: Consumer engagement is central to high-quality cancer service delivery and is a recognised strategy to minimise healthcare-associated harm. Strategies developed to enhance consumer engagement specifically in relation to preventing healthcare harm include questioning health professionals, raising concerns about possible mistakes or risks in care and encouraging patients and caregivers to report suspected errors. Patients from ethnic minority backgrounds are particularly vulnerable to unsafe care, but current engagement strategies have not been developed specifically for (and with) this population. Using an adapted approach to experience-based codesign (EBCD) to support the target population, the aim of the project is to codesign consumer engagement interventions to increase consumer engagement and safety in New South Wales and Victorian cancer inpatient, outpatient and day procedure services. METHODS AND ANALYSIS: A mixed-method project will be undertaken at six study sites. Our EBCD approach includes a preparatory phase in which we will provide training and support to the codesign participants, in addition to recruiting and training consumer cofacilitators for the codesign workshops. The project will follow the EBCD process of gathering and synthesising observational data from each cancer service, with interview data from consumers and staff. With the resulting in-depth understanding of the safety threats commonly experienced by ethnic minority consumers in each site, we will work through feedback events and codesign groups with consumers and staff to determine how they can be more involved with their care to minimise the potential for patient harm. Consumer engagement interventions will be coproduced in each of the six participating services that are tailored to the ethnic minority populations served. ETHICS AND DISSEMINATION: Ethics approval has been obtained from the Western Sydney Local Health District Human Research Ethics Committee. The project will provide strategies for ethnic minority consumers to engage with cancer services to minimise healthcare-associated harm that may be applied to diverse healthcare settings.

Standard-Dose Osimertinib in EGFR-Mutated Non-Small-Cell Lung Adenocarcinoma With Leptomeningeal Disease.

PURPOSE: Leptomeningeal disease (LMD) in epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma is associated with a poor prognosis and limited treatment options. Osimertinib is a potent third-generation EGFR tyrosine kinase inhibitor with confirmed CNS penetration. This study reports on outcomes of patients with EGFR-mutated non-small-cell lung cancer who developed LMD and were subsequently treated with osimertinib. METHODS: We identified patients treated with osimertinib 80 mg PO daily under a compassionate access scheme across nine tertiary Australian institutes between July 2017 and July 2020. Patient demographics, tumor characteristics, and treatment history were collected. Median overall survival, median progression-free survival, disease control rates (DCR), and overall response rates (ORR) were assessed. Kaplan-Meier analysis was performed and descriptive statistics were used. RESULTS: Thirty-nine patients were analyzed of which 74% were female. Exon 19 deletions (49%) and L858R point mutations (41%) were the most common EGFR mutations. Forty-nine percentage of patients were Eastern Cooperative Oncology Group 1. The median duration of osimertinib therapy was 6 months. The extracranial DCR and ORR were 60% and 54%, and the intracranial DCR and ORR were 68% and 53%, respectively. Median overall survival was 10.5 months (95% CI, 8.17 to 15.05 months). CONCLUSION: There are limited treatment options for LMD in EGFR-positive lung cancer, and osimertinib at a dose of 80 mg daily is an active therapeutic option for these patients.

Randomized Evaluation of Cognitive-Behavioral Therapy and Graded Exercise Therapy for Post-Cancer Fatigue.

CONTEXT: Cancer-related fatigue is prevalent and disabling. When persistent and unexplained, it is termed post-cancer fatigue (PCF). Cognitive behavioral therapy (CBT) and graded exercise therapy (GET) may improve symptoms and functional outcomes. OBJECTIVES: To evaluate the outcomes of a randomized controlled trial, which assigned patients with post-cancer fatigue to education, or 12 weeks of integrated cognitive-behavioral therapy (CBT) and graded exercise therapy (GET). METHODS: Three months after treatment for breast or colon cancer, eligible patients had clinically significant fatigue, no comorbid medical or psychiatric conditions that explained the fatigue, and no evidence of recurrence. The CBT/GET arm included individually tailored consultations at approximately two weekly intervals. The education arm included a single visit with clinicians describing the principles of CBT/GET and a booklet. The primary outcome was clinically significant improvement in self-reported fatigue (Somatic and Psychological HEalth REport 0-12), designated a priori as greater than one SD of improvement in fatigue score. The secondary outcome was associated improvement in function (role limitation due to physical health problems-36-Item Short Form Health Survey 0-100) comparing baseline, end treatment (12 weeks), and follow-up (24 weeks). RESULTS: There were 46 patients enrolled, including 43 women (94%), with a mean age of 51 years. Fatigue severity improved in all subjects from a mean of 5.2 (±3.1) at baseline to 3.9 (±2.8) at 12 weeks, suggesting a natural history of improvement. Clinically significant improvement was observed in 7 of 22 subjects in the intervention group compared with 2 of 24 in the education group (P < 0.05, χ2). These subjects also had improvement in functional status compared with nonresponders (P < 0.01, t-test). CONCLUSION: Combined CBT/GET improves fatigue and functional outcomes for a subset of patients with post-cancer fatigue. Further studies to improve the response rate and the magnitude of the benefit are warranted.

Primary pancreatic lymphoma--pancreatic tumours that are potentially curable without resection, a retrospective review of four cases.

BACKGROUND: Primary pancreatic lymphomas (PPL) are rare tumours of the pancreas. Symptoms, imaging and tumour markers can mimic pancreatic adenocarcinoma, but they are much more amenable to treatment. Treatment for PPL remains controversial, particularly the role of surgical resection. METHODS: Four cases of primary pancreatic lymphoma were identified at Prince of Wales Hospital, Sydney, Australia. A literature review of cases of PPL reported between 1985 and 2005 was conducted, and outcomes were contrasted. RESULTS: All four patients presented with upper abdominal symptoms associated with weight loss. One case was diagnosed without surgery. No patients underwent pancreatectomy. All patients were treated with chemotherapy and radiotherapy, and two of four patients received rituximab. One patient died at 32 months. Three patients are disease free at 15, 25 and 64 months, one after successful retreatment. Literature review identified a further 103 patients in 11 case series. Outcomes in our series and other series of chemotherapy and radiotherapy compared favourably to surgical series. CONCLUSION: Biopsy of all pancreatic masses is essential, to exclude potentially curable conditions such as PPL, and can be performed without laparotomy. Combined multimodality treatment, utilising chemotherapy and radiotherapy, without surgical resection is advocated but a cooperative prospective study would lead to further improvement in treatment outcomes.

Treatment of breast cancer 2 (BRCA2)-mutant follicular dendritic cell sarcoma with a poly ADP-ribose polymerase (PARP) inhibitor: a case report.

BACKGROUND: Follicular dendritic cell sarcoma is a rare tumour with clinical behaviour covering a spectrum from indolent to aggressive disease. Treatment recommendations are currently based on case reports and small series describing combinations of surgery, chemotherapy and radiotherapy providing the best patient outcomes. Recent knowledge on molecular aberrations in this disease have not yet impacted on therapeutic decisions. CASE PRESENTATION: We describe a case of progressive follicular dendritic cell sarcoma of the lung and pleura, treated based on knowledge of the tumour's molecular aberrations. The patient was initially treated with surgery, chemotherapy and radiotherapy and developed disease progression. Mutation testing by Caris molecular intelligence demonstrated a breast cancer 2 gene mutation and further treatment with carboplatin and veliparib achieved disease stabilisation. CONCLUSION: Understanding of the molecular profile of rare tumours is key to improve therapeutic decision making and patient outcomes.

Factors Impacting Treatment Choice in the First-Line Treatment of Colorectal Cancer.

INTRODUCTION: To investigate the factors that affect the choice of 5-fluorouracil (5-FU) or its oral alternative, capecitabine, as first-line treatment in patients with colorectal cancer (CRC). METHODS: Patients treated with 5-FU or capecitabine for CRC between January 1, 2011 and December 31, 2013 in a teaching hospital in the Sydney metropolitan area, Australia were identified using the hospital's database MOSAIQ®. The electronic medical record of each patient was manually reviewed to extract factors potentially affecting treatment choice. Logistic regression was used to assess which patient and/or treatment factors could explain the choice between 5-FU or capecitabine. Where it was available in the medical correspondence, the explicit reason for the choice made was extracted. RESULTS: 170 CRC patients were included; 119 on 5-FU, and 51 on capecitabine. The odds of receiving capecitabine as a first-line treatment were positively associated with giving patients a choice in the decision (OR = 17.51, 95% CI: 5.37-57.08). Qualitative data suggest treatment choices were motivated by convenience (oral administration) and tolerability. Time from diagnosis to treatment commencement (OR = 1.02 per month, 95% CI 1.00-1.04) was also found to be positively associated with the choice of capecitabine. The odds of being treated with capecitabine were lower for patients who lived further from the treating hospital (OR = 0.22, 95% CI 0.05-0.94). CONCLUSION: This study suggests that patient choice, favoring oral capecitabine over i.v. 5-FU, was a key factor influencing first-line treatment for CRC in this cohort. To respect their autonomy, patients should be involved in the clinical decision making process.

Resistance surveillance in a BRAF mutant melanoma patient on long-term BRAF-inhibitor treatment.

Treatment responses of BRAF mutant melanoma to BRAF inhibitors are often limited by the development of resistance. This case report describes the use of multiplatform molecular profiling in sequential surgical samples of a treatment-resistant tumour site subjected to ongoing treatment with dabrafenib in a patient with metastatic cutaneous BRAF mutant melanoma. Next-generation sequencing showed the presence of the V600E, fibroblast growth factor receptor 2 (FGFR2), phosphatase and tensin homologue (PTEN) and p53 gene mutations. With a continuous presence of the BRAF V600E, FGFR2 and PTEN mutations and appearances of new mutations in the PTEN gene at R137H and T321fs and p53 R273C genes during ongoing treatment, this case report indicates intratumoural clonal evolution as a resistance mechanism. Two new mutations, the G542E exon 12 mutation variant of the FGFR2 gene and the R273C mutation variant of the p53 gene, are reported for the first time in BRAF mutant melanoma.