What is the value of third-line chemotherapy in advanced gastroesophageal cancer? A 5-year retrospective analysis at a single center.

AIM: The survival benefit of using a non-cross resistant second-line chemotherapy in the third-line setting in metastatic gastroesophageal cancer is unproven. We evaluated the utility of third-line chemotherapy in patients treated at a single institution. METHODS: Between 2010 and 2014, efficacy and toxicity data of patients who received three or more lines of systemic therapies for metastatic gastroesophageal adenocarcinoma at the National Cancer Centre Singapore was retrospectively analyzed. RESULTS: Thirty-two (6%) patients received three or more lines of chemotherapy. The median age and ECOG performance status were 59 years (36-82) and 1 (0-2), respectively. Majority of patients (88%) had tumor located in the stomach and 13 patients (41%) had diffuse histology or poorly cohesive or signet ring cells. Four (12%) patients had HER2-positive disease. Prior therapy was platinum (100%), fluoropyrimidine (97%), taxane (63%), irinotecan (28%), anthracycline (13%) and ramucirumab (3%). Third-line therapy consisted of 24 (75%) monotherapy, 6 (19%) doublet, 1 (3%) triplet chemotherapy and 1 (3%) clinical trial. Monotherapy irinotecan (44%) was most common, followed by docetaxel (19%) and paclitaxel (9%). Of 22 patients evaluable for response, there was 1 (5%) partial response, 9 (41%) stable disease. Median overall survival was 18.3 weeks (4.3-65.1). Of 30 patients evaluable for toxicities, 17 (57%) experienced at least one grade 3 or 4 toxicities. CONCLUSION: The benefit of using non-cross resistant second-line regimens as third-line chemotherapy was small with moderate toxicity. Newer agents such as nivolumab or TAS-102 or clinical trial may be preferred.

General practitioners (GPs) and end-of-life care: a qualitative study of Australian GPs and specialist palliative care clinicians.

OBJECTIVES: General practitioners (GPs) are well placed to be involved in end-of-life care for patients with life-limiting illnesses. However, differing views exist regarding their role. This study aims to explore the views of GPs and specialist palliative care clinicians (SPCCs) on the role that GPs should play in the planning and provision of end-of-life care and important barriers and facilitators to GPs' involvement in end-of-life care including suggestions for improvement. METHODS: Qualitative description methodology using semistructured interviews of 11 GPs and 10 SPCCs. RESULTS: The participants identified two key roles that GPs should play in the planning and provision of end-of-life care: care planning and referring to palliative care services and being the primary clinician in charge of patient care. GPs and SPCCs expressed similar views; however, a significant proportion of the GP participants were not actively involved in end-of-life care. Factors affecting GPs' involvement in end-of-life care included: (1) GP and practice factors including continuity of care, long-term relationships with patients, knowledge and skills in end-of-life care, resource limitations and work patterns; (2) communication and collaboration between GPs and the acute healthcare system and (3) communication and collaboration between GPs and SPCCs. CONCLUSION: GPs have a key role in the planning and provision of end-of-life care. GPs could be encouraged in this role by providing them with education and practical experience in end-of-life care, making changes to remuneration structure, formalised arrangements for shared care and encouraging continuity of care and developing long-term relationship with their patients.

Using intuition or a formal palliative care needs assessment screening process in general practice to predict death within 12 months: A randomised controlled trial.

BACKGROUND: Population ageing will lead to more deaths with an uncertain trajectory. Identifying patients at risk of dying could facilitate more effective care planning. AIM: To determine whether screening for likely death within 12 months is more effective using screening tools or intuition. DESIGN: Randomised controlled trial of screening tools (Surprise Question plus the Supportive and Palliative Care Indicators Tool for Surprise Question positive patients) to predict those at risk of death at 12 months compared with unguided intuition (clinical trials registry: ACTRN12613000266763). SETTING/PARTICIPANTS: Australian general practice. A total of 30 general practitioners (screening tool = 12, intuition = 18) screened all patients ( n = 4365) aged ≥70 years seen at least once in the last 2 years. RESULTS: There were 142 deaths (screening tool = 3.1%, intuition = 3.3%; p = 0.79). General practitioners identified more at risk of dying using Surprise Question (11.8%) than intuition (5.4%; p = 0.01), but no difference with Surprise Question positive then Supportive and Palliative Care Indicators Tool (5.1%; p = 0.87). Surprise Question positive predicted more deaths (53.2%, intuition = 33.7%; p = 0.001), but Surprise Question positive/Supportive and Palliative Care Indicators Tool predictions were similar (5.1%; p = 0.87 vs intuition). There was no difference in proportions correctly predicted to die (Surprise Question = 1.6%, intuition = 1.1%; p = 0.156 and Surprise Question positive/Supportive and Palliative Care Indicators Tool = 1.1%; p = 0.86 vs intuition). Screening tool had higher sensitivity and lower specificity than intuition, but no difference in positive or negative predictive value. CONCLUSION: Screening tool was better at predicting actual death than intuition, but with a higher false positive rate. Both were similarly effective at screening the whole cohort for death. Screening for possible death is not the best option for initiating end-of-life planning: recognising increased burden of illness might be a better trigger.

Safety and efficacy of aflibercept in combination with fluorouracil, leucovorin and irinotecan in the treatment of Asian patients with metastatic colorectal cancer.

AIM: To evaluate the safety and efficacy of the combination therapy of fluorouracil, leucovorin and irinotecan (FOLFIRI) and aflibercept in Asian patients with metastatic colorectal cancer (mCRC), who had progressed after oxaliplatin-based chemotherapy. METHODS: This is a retrospective analysis of 19 mCRC patients who received FOLFIRI and aflibercept (4 mg/kg intravenously) every 2 weeks via a Named Patient Program (supported by Sanofi Aventis) in Singapore. Treatment was administered until disease progression or unacceptable toxicities. Kaplan-Meier method was used to estimate progression-free survival (PFS) and overall survival (OS). Efficacy and toxicities were summarized using descriptive statistics. Statistical analysis was performed using STATA 12.0 software. RESULTS: The majority (84%) of the patients were of chinese ethnicity. The median age was 59 years, with 63.2% of the patients having an Eastern Cooperative Oncology Group status of 1. Four patients (21.1%) achieved partial response and 8 patients (42.1%) achieved stable disease. After a median follow-up of 9.6 months [95% confidence interval (CI), 2.2-13.1 months], the median OS was 11.6 months (95% CI, 6.1 to not-estimable), and median PFS was 4.1 months (95% CI, 2.2-5.9). Majority of the toxicities were grade 1-2, and include leucopenia (84.2%), anemia (73.7%), liver enzyme elevation (68.4%) and fatigue (68.4%). The most frequently reported grade 3 toxicities were neutropenia and neutropenic complications (both 15.8%). All adverse events resolved with supportive management. CONCLUSION: The clinical benefit and safety profile of the combination of FOLFIRI/aflibercept in Asian patients with mCRC are consistent with that of Western population. FOLFIRI/aflibercept may be an appropriate therapeutic option in Asian patients with mCRC previously treated with an oxaliplatin-based regimen.

Outcomes and prognostic factors of post-irradiation and de novo sarcomas of the head and neck: a histologically matched case-control study.

BACKGROUND: This study was designed to compare post-irradiation sarcomas (PIS) and de novo sarcomas (DN) of the head and neck in terms of tumor characteristics, prognostic factors, and survival outcomes. METHODS: All (N=83) head and neck sarcoma patients treated at National Cancer Centre, Singapore (Feb 2002-May 2011) were included: DN (N=60; 72%); PIS (N=23; 28%). Clinicopathologic features and outcomes of all patients and histologically matched pairs were compared. Prognostic factors were identified using univariate and multivariate analyses. RESULTS: Median age, gender, smoking status, and tumor size were not significantly different. Significant differences were seen in histology (most prevalent: PIS-sarcoma-NOS; DN-angiosarcoma) and tumor subsite (most prevalent: PIS-nasal cavity and sinuses; DN-skin). Median latency of PIS development was 16.7 years. PIS patients had shorter overall survival (OS) and disease-specific survival (DSS) compared with DN patients, most clearly seen on histologically matched pair analysis: 2-year OS (PIS: 54%; DN: 83%; P=0.028). Multivariate analyses showed that age>50 years (hazard ratio (HR)=3.68; P=0.007), ever-smokers (HR=2.79; P=0.017), and larger tumor-size (cm) (HR=1.12; P=0.045) were associated with worse OS, and age at >50 years (HR=2.77; P=0.04) and ever-smokers (HR=2.94; P=0.021) were associated with worse DSS. When treated with curative intent, no significant survival difference was noted between DN and PIS patients. CONCLUSIONS: In our cohort, PIS constituted 28% of head and neck sarcomas. Poorer prognosis traditionally associated with PIS compared with DN was not seen amongst patients treated with curative intent.

Demographic and clinical features of 150 pathological gamblers referred to a community addictions programme.

INTRODUCTION: Pathological gambling has been defined as a persistent and recurrent maladaptive gambling behaviour that disrupts personal, family and work life. The present study reports on the sociodemographic features, gambling activity, comorbidity and legal problems in a sample of 150 pathological gamblers who sought treatment from the Community Addiction Management Programme (CAMP), Singapore over a 4-year period from 2002 to 2006. MATERIALS AND METHODS: Data were collected on 150 consecutive subjects who sought treatment at CAMP. Patients were administered a semi-structured interview to elicit demographic data, age of onset, family history, onset games and types of games ever played, largest debt incurred due to gambling, triggers, illegal activities and suicidal attempts by their counsellor. Patients were then assessed by the clinicians to establish the primary and comorbid diagnoses. RESULTS: The mean age of the subjects was 42.5 [standard deviation (SD) 10.2] years. The majority of them were males (87.3%) and of Chinese origin (97.3%). The most common comorbid disorders were mood disorders (n = 22, 14.7%), substance abuse (n = 11, 7.3%) and alcohol abuse or dependence (n = 7, 4.7%). Sixteen (10.7%) subjects had a history of suicidal attempts which had been precipitated by gambling-related issues. CONCLUSIONS: Pathological gambling in our subjects appears to be associated with significant comorbidity and financial problems. These are the preliminary findings and further research is needed regarding the phenomenology, profile, course and response to treatment of pathological gambling disorders.