A serum mesothelin level is a prognostic indicator for patients with malignant mesothelioma in routine clinical practice.

BACKGROUND: Malignant mesothelioma (MM) carries a poor prognosis and response rates to palliative chemotherapy remain low. Identifying patients with MM that are unlikely to respond to chemotherapy could prevent futile treatments and improve patient quality of life. Studies have suggested that soluble mesothelin is a potential biomarker for early diagnosis and prognosis of MM. We set out to explore the utility of serum mesothelin in routine clinical practice. METHODS: We conducted a prospective exploratory study of serum mesothelin levels in 53 consecutive patients with MM at our institution between April 2009 and February 2011. Survival was assessed and analysed by mesothelin level as both continuous and categorical variables using Cox regression models. Differences in response rate between treatment groups were assessed by the Kruskal-Wallis Test. RESULTS: All 53 patients, who had been given study information agreed to participate. The patients' median age was 69 (range 24-90). Median mesothelin level was 2.7 nM and this value was used to dichotomize categories: ≤2.7 nM (low) and >2.7 nM (high). The progression free survival (PFS) for low vs high mesothelin was 8.0 vs 5.1 months (HR 1.8, p-0.058). When mesothelin was accessed as a continuous variable for PFS the HR was 1.03 (95% CI: 1.01-1.06; p=0.013). The overall survival (OS) for low vs high mesothelin was 17.2 vs 11.3 months (HR 1.9, p=0.088). When mesothelin was assessed as a continuous variable for OS the HR was 1.02 (95% CI: 0.99 - 1.04; p=0.073). Thirty patients received chemotherapy of which 18 had a pre-chemotherapy serum mesothelin level. In these 18 patients, the pre-chemotherapy mesothelin level did not correlate with response. CONCLUSIONS: A single random sample provides information about patient prognosis but does not predict treatment response. We suggest further prospective validation of mesothelin testing as a prognostic biomarker.

Discordance between cancer prevalence and training: a need for an increase in oncology education.

The impact of cancer on healthcare is increasing. Therefore, it is key that all doctors receive oncology training. This study surveyed UK undergraduate medical schools to determine the extent of oncology training provided by their curricula. Data on foundation year (FY) and core medical training (CMT) programmes were obtained and analysed for the proportion of oncology posts. Of the responding medical schools, five (36%) had a defined period dedicated to oncology (mean 2 weeks). Four foundation schools were in London, with 10,094 FY posts in 1699 programmes. Of these, 1.5% of post and 8.7% of programmes were in oncology. For CMT offered by the London deanery specialty schools, 11% of CMT post and 48% of programmes included oncology. Oncology was included in 11% posts and 48% programmes offered by the London Deanery specialty schools. Our results show that < 50% of junior doctors receive dedicated undergraduate or postgraduate oncology training. An increase in oncology training is therefore urgently required.

Erlotinib, docetaxel, and gefitinib in sequential cohorts with relapsed non-small cell lung cancer.

BACKGROUND: Both docetaxel and erlotinib improve overall survival over best supportive care in non-small cell lung cancer (NSCLC). We assessed the effectiveness of erlotinib (E) and gefitinib (G) in patients with relapsed NSCLC in both second- and third-line settings, and compared this with that of docetaxel (D), in our clinical practice. METHODS: Sequential cohorts of patients with relapsed advanced stage NSCLC who had been treated with erlotinib (150 mg), gefitinib (250 mg), or docetaxel (75 mg/m(2)) were retrospectively identified from our database. The primary endpoint was overall survival. Secondary endpoints were response rate and progression-free survival. RESULTS: After adjusting for covariates, there was no significant difference in overall survival between the three drugs in both second-line (median E=24; G=25; D=43 weeks, p=0.17), and third-line (median E=31; G=24; D=29 weeks, p=0.61) settings. Response rates were also not statistically significant between the three drugs across both lines of treatment. CONCLUSIONS: Erlotinib, gefitinib, and docetaxel have similar effectiveness in this non-trial setting.

Recurrent responses to non-small cell lung cancer brain metastases with erlotinib.

We report the case of a Caucasian female never smoker with erlotinib sensitive metastatic non-small cell lung cancer in the brain. Having progressed after receiving whole brain radiotherapy, her brain metastases responded both initially and on re-treatment with erlotinib. However, her extra-cranial disease remained erlotinib-resistant throughout. This case demonstrates that brain metastases may be sensitive to erlotinib and also highlights the oligoclonal nature of non-small cell lung cancer reflected by differential tyrosine kinase inhibitor tumour sensitivity. On the basis of this case we suggest that erlotinib should be considered in the treatment paradigm for patients with intra-cranial disease and propose further study into the continued use of this drug in the situation where there is a differential response.

The association of chemotherapy induced neutropenia on treatment outcomes in small cell lung cancer.

BACKGROUND: Chemotherapy induced neutropenia has been shown to be associated with improved treatment outcomes in selected solid tumours. We studied the association of chemotherapy induced neutropenia with treatment related outcomes in small cell lung cancer (SCLC). METHODS: This is a retrospective analysis of patients receiving chemotherapy for SCLC at the Royal Marsden Hospital, UK over an 8 year period. The chemotherapy included Carboplatin AUC 5, IV and Etoposide 100mg/m(2) IV on day 1 and 100mg/m(2) PO, B.I.D. on day 2 and 3 every 21 days. Patients were stratified into two groups (A) those experiencing grades 0-2 neutropenia and group (B) those experiencing grades 3-4 neutropenia. The outcomes studied were response rate, time to progression (TTP) and overall survival (OS). RESULTS: 173 patients were studied. The median age 64 (range 39-83) and M/F ratio was 112:61. The response rates in groups A and B was 90% versus 90%, p=1.0. The median TTP in groups A and B was 30 and 38 weeks, p=0.05. The median OS in groups A and B was 47 weeks versus 60 weeks, p=0.008. The differences in TTP and OS were not significant in patients with extensive stage disease. CONCLUSIONS: Occurrence of chemotherapy induced grade 3 or 4 neutropenia correlated with OS in patients with SCLC receiving carboplatin and etoposide chemotherapy. Trials exploring controlled, safe intra-patient dose escalation with the intent of achieving grade 3 or 4 neutropenia in patients with SCLC are warranted.

An Association of Cancer Physicians' strategy for improving services and outcomes for cancer patients.

The Association of Cancer Physicians in the United Kingdom has developed a strategy to improve outcomes for cancer patients and identified the goals and commitments of the Association and its members.

Early response to platinum-based first-line chemotherapy in non-small cell lung cancer may predict survival.

INTRODUCTION: Response rates in the palliative treatment of non-small cell lung cancer, with combination platinum-based chemotherapy, vary from 20% to 40%, leaving a large number with either stable or progressive disease. We examined radiographic response after two courses of platinum-based induction chemotherapy to see whether this is an early predictor of outcome. METHODS: In this retrospective study, 320 patients with stage III/IV NSCLC were identified who received 4 or more courses of first-line platinum-based chemotherapy and attained partial response (PR) or stable disease (SD). RESULTS: After two courses, 115 patients attained PR and 205 SD. Cox regression analysis shows that response after two courses of chemotherapy remains an independent significant prognostic factor for survival. The 2-year survival for patients attaining PR after two courses (n = 115) was 23% compared with 11% (n = 205) for those with SD (p = 0.002). Patients who achieve an objective response after two courses also have a better symptomatic response (p = 0.003) and it was significantly longer (p = 0.04). Of the 205 with SD, 51 attained PR with four courses, whereas 154 (48%) remained with SD; there was no difference in survival outcome of these two groups. CONCLUSIONS: These data suggest that NSCLC patients who only have SD after two cycles of first-line chemotherapy have poorer survival outcome and less symptomatic benefit than those in PR. Trials looking at change in management at this point are warranted.