Clare Hodgson

Prevalence and heterogeneity of circulating tumour cells in metastatic cutaneous melanoma.

We previously demonstrated that circulating tumour cells (CTCs) are detectable by the MelCAM and high molecular weight melanoma-associated antigen (HMW-MAA)-dependent CellSearch platform. However, CTCs which do not express these capture and detection markers are not detectable by CellSearch. Consequently, we explored the use of isolation by size of epithelial tumour cells (ISET), a marker independent, filtration-based device to determine the prevalence and heterogeneity of CTCs in metastatic cutaneous melanoma patients. Ninety patients were prospectively recruited and blood samples taken before treatment. Patients’ blood was filtered using the ISET platform. CTCs were enumerated using dual immunohistochemistry with positive selection by S100 expression and exclusion of leucocytes and endothelial cells expressing CD45 or CD144, respectively. A panel of markers (Melan-A, MITF, MelCAM, high molecular melanoma-associated antigen, CD271 and MAGEC) was also examined. Fifty-one patients (57%) had CTCs (range 1–44 CTCs/4 ml blood) and 12 patients also had circulating tumour microemboli. Seven patients had S100− CTCs, 11 patients’ CTCs were S100+ and 33 patients had S100+ and S100− CTCs. Substantial intrapatient and interpatient heterogeneity was observed for all other melanoma-associated markers. CTCs in metastatic cutaneous melanoma are detectable using the flexible marker-independent ISET platform. CTCs display significant marker expression heterogeneity implying that marker-dependent platforms would not detect all CTCs and multimarker assays are now required to reveal the biological significance of this CTC heterogeneity.

Quantification of skeletal metastases in castrate resistant prostate cancer predicts progression free and overall survival.

To report a simplified and effective method for substratification of M1 castrate‐resistant prostate cancer (CRPC) by correlating progression‐free (PFS) and overall survival (OS) with simple quantification of skeletal metastases.

Characterisation and risk assessment of venous thromboembolism in gastrointestinal cancers

AIM To characterise venous thromboembolism (VTE) in gastrointestinal cancer and assess the clinical utility of risk stratification scoring. METHODS We performed a retrospective analysis using electronic patient records of 910 gastro-oesophageal (GO) cancer and 1299 colorectal cancer (CRC) patients referred to a tertiary cancer centre to identify the incidence of VTE, its relationship to chemotherapy and impact on survival. VTE risk scores were calculated using the Khorana index. Patients were classified as low risk (0 points), intermediate risk (1 to 2 points) or high risk (3 points). Data was analysed to determine the sensitivity of the Khorana score to predict VTE. RESULTS The incidence of VTE was 8.9% for CRC patients and 9.7% for GO cancer patients. Pulmonary emboli (PE) were more common in advanced than in localised CRC (50% vs 21% of events respectively) and lower limb deep vein thrombosis (DVT) were more common in localised than in advanced CRC (62% vs 39% of events respectively). The median time to VTE from cancer diagnosis was 8.3 mo for CRC patients compared to 6.7 mo in GO cancer. In localised CRC median time to VTE was 7.1 mo compared with 10.1 mo in advanced CRC. In contrast in GO cancer, the median time to VTE was 12.5 mo in localised disease and 6.8 mo in advanced disease. No survival difference was seen between patients with and without VTE in this cohort. The majority of patients with CRC in whom VTE was diagnosed had low or intermediate Khorana risk score (94% for localised and 97% in advanced CRC). In GO cancer, all patients scored either intermediate or high risk due to the primary site demonstrating a limitation of the risk assessment score in discriminating high and low risk patients with GO cancers. Additional risk factors were identified in this cohort including surgery, chemotherapy or hospital admission. Overall, 81% of patients with CRC and 77% of patients with GO cancer had one or more of these factors within 4 wk prior to diagnosis VTE. These should be factored into clinical risk assessment scores. CONCLUSION The Khorana score has low sensitivity for thrombotic events in CRC and cannot discriminate low risk patients in high risk cancer sites such as GO cancer.

Changes in prostate apparent diffusion coefficient values during radiotherapy after neo-adjuvant hormones

Background: Changes in prostate cancer apparent diffusion coefficient (ADC) derived from diffusion-weighted magnetic resonance imaging (MRI) provide a noninvasive method for assessing radiotherapy response. This may be attenuated by neoadjuvant hormone therapy (NA-HT). We investigate ADC values measured before, during and after external beam radiotherapy (EBRT) following NA-HT. Methods: Patients with ⩾T2c biopsy-proven prostate cancer receiving 3 months of NA-HT plus definitive radiotherapy were prospectively identified. All underwent ADC-MRI scans in the week before EBRT, in the third week of EBRT and 8 weeks after its completion. Imaging was performed at 1.5 T. The tumour, peripheral zone (PZ) and central zone (CZ) of the prostate gland were identified and median ADC calculated for each region and time point. Results: Between September and December 2014, 15 patients were enrolled (median age 68.3, range 57–78) with a median Gleason score of 7 (6–9) and prostate-specific antigen (PSA) at diagnosis 14 (3–197) ng/ml. Median period of NA-HT prior to first imaging was 96 days (69–115). All patients completed treatment. Median follow up was 25 months (7–34), with one patient relapsing in this time. Thirteen patients completed all imaging as intended, one withdrew after one scan and another missed the final imaging. PZ and CZ could not be identified in one patient. Median tumour ADC before, during and post radiotherapy was 1.24 × 10−3 mm2/s (interquartile range 0.16 × 10−3 mm2/s), 1.31 × 10−3 mm2/s (0.22 × 10−3 mm2/s), then 1.32 × 10−3 mm2/s (0.13 × 10−3 mm2/s) respectively (p > 0.05). There was no significant difference between median tumour and PZ or CZ ADC at any point. Gleason score did not correlate with ADC values. Conclusions: Differences in ADC parameters of normal and malignant tissue during EBRT appear attenuated by prior NA-HT. The use of changes in ADC as a predictive tool in this group may have limited utility.

The use of volunteers to implement electronic patient reported outcomes in lung cancer outpatient clinics

Highlights • 104 eligible lung cancer patients were approached, 86 (83%) consented to take part.• At 1st attempt 69% of patients completed the ePRO questionnaire without assistance.• Assistance was defined as verbal/physical help to complete the ePRO questionnaire.• Most patients requiring help had a companion that could have provided assistance.• More patients preferred electronic than paper questionnaires.

Outcomes of radiosensitisation in elderly patients with advanced bladder cancer

INTRODUCTION There is little evidence to guide treatment in elderly patients with muscle invasive bladder cancer (MIBC). We evaluated the efficacy and tolerability of concurrent radical radiotherapy with gemcitabine radiosensitisation (GemX) in elderly patients with MIBC and compared outcomes to those from the bladder carbogen and nicotinamide (BCON) phase III trial. MATERIALS AND METHODS Data were retrospectively analysed for patients who received GemX from two oncology centres in the UK. Elderly was defined as aged ≥75 at the start of GemX. Following transurethral resection of bladder tumour, patients received neo-adjuvant platinum-based chemotherapy followed by radiotherapy concurrently with weekly gemcitabine. A separate, age-specific analysis was performed in the BCON cohort. Overall survival (OS), disease specific survival (DSS) and local progression free survival (LPFS) were evaluated using Kaplan-Meier methodology and Cox proportional hazards regression. RESULTS Out of 167 patients who received GemX, 61 were elderly (36.5%) with a median age of 78 years. Elderly patients had worse performance status (p = 0.020) and co-morbidities (p = 0.030). A similar proportion of patients received planned dose radiotherapy in both groups (p = 0.260), although fewer elderly patients received all four cycles of concurrent chemotherapy (p = 0.017) due to toxicity. For OS, age had some prognostic power; HR 1.04 (95% CI 1.00-1.08; p = 0.068). Overall survival and LPFS in elderly patients were comparable between CON and GemX (HR 1.13, 95% CI 0.69-1.85; p = 0.616 and HR 0.85, 95% CI 0.41-1.74; p = 0.659 respectively). DISCUSSION Radiosensitisation is safe and effective and should be considered for fit elderly patients with MIBC.

Cell-death, inflammation, tumor-burden and proliferation blood biomarkers predict lung cancer radiotherapy response and correlate with tumor volume and proliferation imaging

Micro‐Abstract In this study we evaluated, to our knowledge, the largest blood biomarker panel ever reported. Baseline interleukin‐1b and neutrophil count and early‐treatment cytokeratin‐19 antigen predicted lung cancer radiotherapy response. Baseline angioprotein‐1 and hepatocyte growth factor (HGF) significantly correlated with the gross tumor volume. Changes in vascular cell adhesion molecule 1 (VCAM‐1) correlated with proliferation imaging, highlighting for the first time a potential role of blood biomarkers as imaging surrogates. Introduction There is an unmet need to develop noninvasive biomarkers to stratify patients in drug‐radiotherapy trials. In this pilot study we investigated lung cancer radiotherapy response and toxicity blood biomarkers and correlated findings with tumor volume and proliferation imaging. Patients and Methods Blood samples were collected before and during (day 21) radiotherapy. Twenty‐six cell‐death, hypoxia, angiogenesis, inflammation, proliferation, invasion, and tumor‐burden biomarkers were evaluated. Clinical and laboratory data were collected. Univariate analysis was performed on small‐cell and non–small‐cell lung cancer (NSCLC) whereas multivariate analysis focused on NSCLC. Results Blood samples from 78 patients were analyzed. Sixty‐one (78.2%) harbored NSCLC, 48 (61.5%) received sequential chemoradiotherapy. Of tested baseline biomarkers, undetectable interleukin (IL)‐1b (hazard ratio [HR], 4.02; 95% confidence interval [CI], 2.04‐7.93; P < .001) was the only significant survival covariate. Of routinely collected laboratory tests, high baseline neutrophil count was a significant survival covariate (HR, 1.07; 95% CI, 1.02‐1.11; P = .017). Baseline IL‐1b and neutrophil count were prognostic for survival in a multivariate model. The addition of day‐21 cytokeratin‐19 antigen modestly improved this models survival prediction (concordance probability, 0.75‐0.78). Chemotherapy (P < .001) and baseline keratinocyte growth factor (P = .019) predicted acute esophagitis, but only chemotherapy remained significant after Bonferroni correction. Baseline angioprotein‐1 and hepatocyte growth factor showed a direct correlation with tumor volume whereas changes in vascular cell adhesion molecule 1 showed significant correlations with 18F‐fluorothymidine (FLT) positron emission tomography (PET). Conclusion Select biomarkers are prognostic after radiotherapy in this lung cancer series. The correlation between circulating biomarkers and 18F‐FLT PET is shown, to our knowledge for the first time, highlighting their potential role as imaging surrogates.