Patient knowledge, personal experience, and impact of the first wave of the COVD-19 pandemic in an Irish oncology cohort.

BACKGROUND: Oncology patients have had to make many changes to minimise their exposure to COVID-19, causing stress. Despite education, some patients still do not recognise potential COVID symptoms. AIMS: We assessed patient knowledge of COVID, and its impact on their behaviours, concerns, and healthcare experience. METHODS: A 16-page questionnaire was distributed to 120 oncology patients attending the day unit of a tertiary Irish cancer centre for systemic anti-cancer therapy (May/June 2020). The Irish 7-day COVID incidence during this period ranged from 2 to 11 cases/100,000 people. RESULTS: One hundred and one responses were received, 1% had tested positive for COVID, and 31% had undergone testing. Participant insight into their knowledge about COVID and their own behaviour was limited in some cases. Seventy-five percent reported total compliance with restrictions, but many were not fully compliant. Self-reported confidence in knowledge was high, but did not predict demonstrated knowledge. Sixty percent did not recognise two or more symptoms; 40% did not self-identify as high-risk. Patients reported more health-related worry (72%), loneliness (51%), and lower mood (42%) since the pandemic began. Financial toxicity worsened, with increased financial worry (78%), reductions in household income (40%), and increased costs due to lockdown (62%). Use of facemasks introduced new communications barriers for 67% of those with hearing loss. CONCLUSIONS: Despite self-reported confidence in knowledge, some patient's recognition of COVID symptoms and the preventative strategies they should use are not optimal, highlighting the need for further education in this regard. COVID has been a significant stressor for patients and more practical, financial, and psychological supports are needed.

Feasibility and preliminary efficacy of a physiotherapy-led remotely delivered physical activity intervention in cancer survivors using wearable technology. The IMPETUS trial.

BACKGROUND: Physical activity levels are low in cancer survivors. Remotely delivered programs which harness wearable technology may potentially be beneficial. OBJECTIVE: To evaluate the feasibility and preliminary efficacy of a remotely delivered, physical activity intervention which harnessed wearable technology. METHODS: This single arm pre-post longitudinal study included cancer survivors who had completed treatment in the preceding 3 years. Participants were supplied with a Fitbit One® or Flex® for 12 weeks. Physical activity goals were discussed during support phone calls. Outcome measures, assessed at baseline (T1), 12 weeks (T2), and 24 weeks (T3), included feasibility (recruitment, adherence, safety, acceptability) and efficacy [physical activity (Godin leisure time Index, ActiGraph GT3X+), quality of life (functional assessment of cancer therapy - general, short form 36 physical functioning component), functional capacity (six-minute walk test)]. RESULTS: Forty-five participants completed T1 assessments (10 males, 35 females). Thirty-nine (86.6%) of those underwent assessment at T2 and 31 (68.8%) at T3. The intervention was perceived positively with no adverse effects. There were increases in functional capacity (six-minute walk test, p = .002) between T1-T3, an increase in quality of life [short form 36 physical functioning measure (p = .0035), functional assessment of cancer total score (p = .02)] and self-report physical activity levels (p = .000123) between T1-T2, although effect sizes were generally low (d = 0.180 to d = 0.418). Objectively measured physical activity did not change. CONCLUSION: A physical activity intervention including wearable technology was safe, feasible, and well received by cancer survivors. An intervention based on this proof of concept should be followed up in further studies.

Weekly dose-dense chemotherapy in first-line epithelial ovarian, fallopian tube, or primary peritoneal cancer treatment (ICON8): overall survival results from an open-label, randomised, controlled, phase 3 trial.

BACKGROUND: Standard-of-care first-line chemotherapy for epithelial ovarian cancer is carboplatin and paclitaxel administered once every 3 weeks. The JGOG 3016 trial reported significant improvement in progression-free and overall survival with dose-dense weekly paclitaxel and 3-weekly (ie, once every 3 weeks) carboplatin. However, this benefit was not observed in the previously reported progression-free survival results of ICON8. Here, we present the final coprimary outcomes of overall survival and updated progression-free survival analyses of ICON8. METHODS: In this open-label, randomised, controlled, phase 3 trial (ICON8), women aged 18 years or older with newly diagnosed stage IC-IV epithelial ovarian, primary peritoneal, or fallopian tube carcinoma (here collectively termed ovarian cancer, as defined by International Federation of Gynecology and Obstetrics [FIGO] 1988 criteria) and an Eastern Cooperative Oncology Group performance status of 0-2 were recruited from 117 hospitals with oncology departments in the UK, Australia and New Zealand, Mexico, South Korea, and Ireland. Patients could enter the trial after immediate primary surgery (IPS) or with planned delayed primary surgery (DPS) during chemotherapy, or could have no planned surgery. Participants were randomly assigned (1:1:1), using the Medical Research Council Clinical Trials Unit at University College London randomisation line with stratification by Gynecologic Cancer Intergroup group, FIGO disease stage, and outcome and timing of surgery, to either 3-weekly carboplatin area under the curve (AUC)5 or AUC6 and 3-weekly paclitaxel 175 mg/m2 (control; group 1), 3-weekly carboplatin AUC5 or AUC6 and weekly paclitaxel 80 mg/m2 (group 2), or weekly carboplatin AUC2 and weekly paclitaxel 80 mg/m2 (group 3), all administered via intravenous infusion for a total of six 21-day cycles. Coprimary outcomes were progression-free survival and overall survival, with comparisons done between group 2 and group 1, and group 3 and group 1, in the intention-to-treat population. Safety was assessed in all patients who started at least one chemotherapy cycle. The trial is registered on ClinicalTrials.gov, NCT01654146, and ISRCTN registry, ISRCTN10356387, and is closed to accrual. FINDINGS: Between June 6, 2011, and Nov 28, 2014, 1566 patients were randomly assigned to group 1 (n=522), group 2 (n=523), or group 3 (n=521). The median age was 62 years (IQR 54-68), 1073 (69%) of 1566 patients had high-grade serous carcinoma, 1119 (71%) had stage IIIC-IV disease, and 745 (48%) had IPS. As of data cutoff (March 31, 2020), with a median follow-up of 69 months (IQR 61-75), no significant difference in overall survival was observed in either comparison: median overall survival of 47·4 months (95% CI 43·1-54·8) in group 1, 54·8 months (46·6-61·6) in group 2, and 53·4 months (49·2-59·6) in group 3 (group 2 vs group 1: hazard ratio 0·87 [97·5% CI 0·73-1·05]; group 3 vs group 1: 0·91 [0·76-1·09]). No significant difference was observed for progression-free survival in either comparison and evidence of non-proportional hazards was seen (p=0·037), with restricted mean survival time of 23·9 months (97·5% CI 22·1-25·6) in group 1, 25·3 months (23·6-27·1) in group 2, and 24·8 months (23·0-26·5) in group 3. The most common grade 3-4 adverse events were reduced neutrophil count (78 [15%] of 511 patients in group 1, 183 [36%] of 514 in group 2, and 154 [30%] of 513 in group 3), reduced white blood cell count (22 [4%] in group 1, 80 [16%] in group 2, and 71 [14%] in group 3), and anaemia (26 [5%] in group 1, 66 [13%] in group 2, and 24 [5%] in group 3). No new serious adverse events were reported. Seven treatment-related deaths were reported (two in group 1, four in group 2, and one in group 3). INTERPRETATION: In our cohort of predominantly European women with epithelial ovarian cancer, we found that first-line weekly dose-dense chemotherapy did not improve overall or progression-free survival compared with standard 3-weekly chemotherapy and should not be used as part of standard multimodality front-line therapy in this patient group. FUNDING: Cancer Research UK, Medical Research Council, Health Research Board in Ireland, Irish Cancer Society, and Cancer Australia.

Circulating Tumour Cell Numbers Correlate with Platelet Count and Circulating Lymphocyte Subsets in Men with Advanced Prostate Cancer: Data from the ExPeCT Clinical Trial (CTRIAL-IE 15-21).

Interactions between circulating tumour cells (CTCs) and platelets are thought to inhibit natural killer(NK)-cell-induced lysis. We attempted to correlate CTC numbers in men with advanced prostate cancer with platelet counts and circulating lymphocyte numbers. Sixty-one ExPeCT trial participants, divided into overweight/obese and normal weight groups on the basis of a BMI ≥ 25 or <25, were randomized to participate or not in a six-month exercise programme. Blood samples at randomization, and at three and six months, were subjected to ScreenCell filtration, circulating platelet counts were obtained, and flow cytometry was performed on a subset of samples (n = 29). CTC count positively correlated with absolute total lymphocyte count (r2 = 0.1709, p = 0.0258) and NK-cell count (r2 = 0.49, p < 0.0001). There was also a positive correlation between platelet count and CTC count (r2 = 0.094, p = 0.0001). Correlation was also demonstrated within the overweight/obese group (n = 123, p < 0.0001), the non-exercise group (n = 79, p = 0.001) and blood draw samples lacking platelet cloaking (n = 128, p < 0.0001). By flow cytometry, blood samples from the exercise group (n = 15) had a higher proportion of CD3+ T-lymphocytes (p = 0.0003) and lower proportions of B-lymphocytes (p = 0.0264) and NK-cells (p = 0.015) than the non-exercise group (n = 14). These findings suggest that CTCs engage in complex interactions with the coagulation cascade and innate immune system during intravascular transit, and they present an attractive target for directed therapy at a vulnerable stage in metastasis.

Assessing the Quality of Care Delivered to Transgender and Gender Diverse Patients with Cancer in Ireland: A Case Series.

INTRODUCTION: "Transgender" and "gender diverse" are umbrella terms encompassing those whose gender identities or expressions differ from those typically associated with the sex they were assigned at birth. There is scant global information on cancer incidence, outcome, and mortality for this cohort. This group may present with advanced cancer, have mistrust in health care services and report anxiety and depression at higher frequencies, a finding often seen in marginalized groups because of minority stress. MATERIALS AND METHODS: Medical oncologists were contacted by secure email to identify patients who self-identify as transgender and gender diverse in three Irish hospitals. Five patients were identified. A retrospective chart review was conducted and a pseudonymized patient survey was distributed. RESULTS: All patients included in our chart review (n = 5) were diagnosed with advanced disease on initial diagnosis. Two patients identified as men, two as women, and one as a transwoman. Two of five patients' health record charts reflected a name or gender change. Three patients had gender transitioning treatment postponed. Assessing comorbidities, it was seen that four patients required psychiatry input. Predominant issues noted in our patient survey by the two respondents (n = 2) were "mis-gendering," lack of a gender-neutral hospital environment, lack of inclusion in cancer groups, and barriers in changing name and/or sex on hospital records. CONCLUSION: Components of care requiring revision include patient accessible pathways to change names and gender on health records, earlier access to psychological support and targeted screening and support groups. Resources for hospital staff to improve awareness of correct terminology and to provide gender neutral facilities are worthwhile. IMPLICATIONS FOR PRACTICE: The implications for practice on an international level include patient-friendly pathways for changing hospital name and gender so that patients may feel comfortable using wristbands. The need for international screening guidelines for transgender patients and national transgender cancer support groups is highlighted. On a day-to-day level for providers, the correct use of pronouns makes a big difference to patients. Asking about preferred pronoun on first visit and noting on patient's file is worthwhile. It is important for providers to know that increased psychological support should be offered early on first clinic visit and engaged with as necessary when patient has a history of anxiety or depression. Providers should discuss openly that some gender transitioning treatment will be postponed because of cancer care and refer to both the physical and psychological sequelae of this. Asking transgender patients which room or bathroom they would prefer when rooms are gendered is essential.

Prevalence of Insomnia in an Oncology Patient Population: An Irish Tertiary Referral Center Experience.

BACKGROUND: The NCCN Guidelines for Survivorship recommend dedicated sleep assessment. Reported insomnia prevalence in the general Irish population is 6% to 15%. Reported insomnia prevalence internationally among new/recently diagnosed patients with cancer varies from 30.9% to 54.3%. Insomnia prevalence has not been previously quantified in an Irish oncology cohort. METHODS: A 40-item questionnaire was prospectively administered to ambulatory patients with cancer aged ≥18 years. Prespecified criteria to define insomnia syndrome combined those of the International Classification of Sleep Disorders, version 1, and the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). The Hospital Anxiety and Depression Scale-Depression/Anxiety (HADS-D/A) was used to screen for potential confounding variables. RESULTS: The response rate to the questionnaire was 87% (294/337). The predominant respondent age group was 55 to 64 years (26%; 77/294), 70.7% were female (208/294), and the most common cancer subtypes were breast (37.4%), colorectal (12.9%), and lung (12.2%). A total of 62% (183/294) of patients reported sleep disturbance after diagnosis, 63% (115/183) reported moderate/severe distress related to this disturbance, and 37% (61/183) reported a significant impact on physical function. Although 33% (98/294) met insomnia syndrome criteria, only 34% (33/98) of these patients had a preexisting history of sleep disturbance. Female sex, age <65 years, cancer subtype, alcohol consumption, and HADS-D/A ≥11 were associated with statistically significant higher odds ratios (OR) of insomnia syndrome. Multivariate analysis identified breast cancer (OR, 3.17; P=.01), age <65 years (OR, 1.8; P=.03), and alcohol consumption (OR, 2.3; P=.005) as independent predictors of insomnia syndrome. CONCLUSIONS: Insomnia syndrome prevalence in this cohort is comparable to that reported previously and supports dedicated sleep assessment. This study identifies potentially modifiable risk factors for insomnia and demonstrates additional utility of the HADS score in identifying patients at risk.

Understanding and Attitudes toward Cancer Clinical Trials among Patients with a Cancer Diagnosis: National Study through Cancer Trials Ireland.

Cancer clinical trials (CCTs) are critical to translation and development of better therapies to improve outcomes. CCTs require adequate patient involvement but accrual rates are low globally. Several known barriers impede participation and knowing how subpopulations differ in understanding of CCTs can foster targeted approaches to aid accrual and advance cancer treatments. We conducted the first nationwide survey of 1089 patients attending 14 Irish cancer centres, assessing understanding of fundamental concepts in CCT methodology and factors that influence participation, to help tailor patient support for accrual to CCTs. Two-thirds (66%) of patients reported never having been offered a CCT and only 5% of those not offered asked to participate. Misunderstanding of clinical equipoise was prevalent. There were differences in understanding of randomisation of treatment by age (p < 0.0001), ethnicity (p = 0.035) and marital status (p = 0.013), and 58% of patients and 61% previous CCT participants thought that their doctor would ensure better treatment in CCTs. Females were slightly more risk averse. Males indicated a greater willingness to participate in novel drug trials (p = 0.001, p = 0.003). The study identified disparities in several demographics; older, widowed, living in provincial small towns and fewer years-educated patients had generally poorer understanding of CCTs, highlighting requirements for targeted support in these groups.

Weekly platinum-based chemotherapy versus 3-weekly platinum-based chemotherapy for newly diagnosed ovarian cancer (ICON8): quality-of-life results of a phase 3, randomised, controlled trial.

BACKGROUND: The ICON8 study reported no significant improvement in progression-free survival (a primary endpoint) with weekly chemotherapy compared with standard 3-weekly treatment among patients with epithelial ovarian cancer. All ICON8 patients were eligible to take part in the accompanying health-related quality-of-life study, which measured the effect of treatment on self-reported wellbeing, reported here. METHODS: In this open-label, randomised, controlled, phase 3, three-arm, Gynecologic Cancer Intergroup (GCIG) trial done at 117 hospital sites in the UK, Australia, New Zealand, Mexico, South Korea, and Republic of Ireland, women (aged at least 18 years) with newly diagnosed, histologically confirmed International Federation of Gynecology and Obstetrics stage IC-IV ovarian cancer and an Eastern Cooperative Oncology Group performance status of 0-2 were randomly assigned (1:1:1) centrally using minimisation to group 1 (intravenous carboplatin area under the curve [AUC]5 or AUC6 and 175 mg/m2 intravenous paclitaxel every 3 weeks), group 2 (carboplatin AUC5 or AUC6 every 3 weeks and 80 mg/m2 paclitaxel weekly), or group 3 (carboplatin AUC2 weekly and 80 mg/m2 paclitaxel weekly). Randomisation was stratified by GCIG group, disease stage, and outcome and timing of surgery. Patients and clinicians were not masked to treatment assignment. Patients underwent immediate or delayed primary surgery according to clinicians' choice. Patients were asked to complete European Organisation for Research and Treatment of Cancer QLQ-C30 and QLQ-OV28 questionnaires at enrolment, before each chemotherapy cycle, then 6-weekly up to 9 months, 3-monthly up to 2 years, and 6-monthly up to 5 years. Quality of life was a prespecified secondary outcome of the ICON8 study. Within the quality-of-life study, the co-primary endpoints were QLQ-C30 global health score at 9 months (cross-sectional analysis) and mean QLQ-C30 global health score from randomisation to 9 months (longitudinal analysis). Data analyses were done on an intention-to-treat basis. The trial is registered on ClinicalTrials.gov, NCT01654146 and ISRCTN Registry, ISRCTN10356387, and is currently in long-term follow up. FINDINGS: Between June 6, 2011, and Nov 28, 2014, 1566 patients were recruited into ICON8 (522 were included in group 1, 523 in group 2, and 521 in group 3). Baseline quality-of-life questionnaires were completed by 1438 (92%) of 1566 patients and 9-month questionnaires by 882 (69%) of 1280 patients. We observed no significant difference in global health score at 9 months (cross-sectional analysis) between study groups (group 2 vs group 1, difference in mean score 2·3, 95% CI -0·4 to 4·9, p=0·095; group 3 vs group 1, -0·8, -3·8 to 2·2, p=0·61). Using longitudinal analysis, we found lower global health scores for those receiving weekly paclitaxel than for those receiving 3-weekly chemotherapy (group 2 vs group 1, mean difference -1·8, 95% CI -3·6 to -0·1, p=0·043; group 3 vs group 1, -2·9, -4·7 to -1·1, p=0·0018). INTERPRETATION: We found no evidence of a difference in global quality of life between treatment groups at 9 months; however, patients receiving weekly treatment reported lower mean quality of life across the 9-month period after randomisation. Taken together with the lack of progression-free survival benefit, these findings do not support routine use of weekly paclitaxel-containing regimens in the management of newly diagnosed ovarian cancer. FUNDING: Cancer Research UK, Medical Research Council, Health Research Board Ireland, Irish Cancer Society, and Cancer Australia.

Perceptions of eHealth-Enabled Physical Activity Interventions Among Cancer Survivors: Mixed Methods Study.

BACKGROUND: Achieving adequate levels of physical activity (PA) is especially important for cancer survivors to mitigate the side effects of cancer and its treatment as well as for other health benefits. Electronic health (eHealth)-based PA interventions may offer feasible alternatives to traditionally delivered programs and optimize physical recovery after a cancer diagnosis, but perspectives of cancer survivors on this new delivery medium have not been extensively explored. OBJECTIVE: The overall aim was to explore participants' perspectives of eHealth-enabled PA interventions to inform the design of a future intervention among cancer survivors. METHODS: The study took place in a designated cancer center in Dublin, Ireland. A preceding questionnaire-based study was conducted primarily to establish interest in participating in subsequent eHealth-based studies. A follow-on focus group study was conducted to explore the concept of eHealth-based PA interventions for cancer survivors. The data were analyzed using thematic analysis. RESULTS: The questionnaire-based study (N=102) indicated that participants had a high level of interest in participating in follow-on eHealth-based studies. The focus group study (n=23) indicated that, despite some trepidation, overall positivity was expressed by participants toward the concept of eHealth-based PA interventions. Four themes were generated: (1) Health impact, including PA as a barrier and as a motivating factor, (2) Education needs, which emphasized the need for integrated information about PA and to increase technical literacy, (3) Goal setting, which should be integrated within the technical specification as a motivating factor, and (4) Support needs, as well as the importance of personalized human interaction, in tandem with technology. CONCLUSIONS: Qualitative research at the pretrial phase adds value to the design of a complex intervention and is especially useful in an area such as eHealth. The findings highlighted an interest in participating in eHealth-focused research as well as barriers, training needs, and key design features that can be applied to optimize the design of future eHealth-based PA interventions in cancer.

Weekly dose-dense chemotherapy in first-line epithelial ovarian, fallopian tube, or primary peritoneal carcinoma treatment (ICON8): primary progression free survival analysis results from a GCIG phase 3 randomised controlled trial.

BACKGROUND: Carboplatin and paclitaxel administered every 3 weeks is standard-of-care first-line chemotherapy for epithelial ovarian cancer. The Japanese JGOG3016 trial showed a significant improvement in progression-free and overall survival with dose-dense weekly paclitaxel and 3-weekly carboplatin. In this study, we aimed to compare efficacy and safety of two dose-dense weekly regimens to standard 3-weekly chemotherapy in a predominantly European population with epithelial ovarian cancer. METHODS: In this phase 3 trial, women with newly diagnosed International Federation of Gynecology and Obstetrics stage IC-IV epithelial ovarian cancer were randomly assigned to group 1 (carboplatin area under the curve [AUC]5 or AUC6 and 175 mg/m2 paclitaxel every 3 weeks), group 2 (carboplatin AUC5 or AUC6 every 3 weeks and 80 mg/m2 paclitaxel weekly), or group 3 (carboplatin AUC2 and 80 mg/m2 paclitaxel weekly). Written informed consent was provided by all women who entered the trial. The protocol had the appropriate national research ethics committee approval for the countries where the study was conducted. Patients entered the trial after immediate primary surgery, or before neoadjuvant chemotherapy with subsequent planned delayed primary surgery. The trial coprimary outcomes were progression-free survival and overall survival. Data analyses were done on an intention-to-treat basis, and were powered to detect a hazard ratio of 0·75 in progression-free survival. The main comparisons were between the control group (group 1) and each of the weekly research groups (groups 2 and 3). FINDINGS: Between June 6, 2011, and Nov 28, 2014, 1566 women were randomly assigned to treatment. 72% (365), completed six protocol-defined treatment cycles in group 1, 60% (305) in group 2, and 63% (322) in group 3, although 90% (454), 89% (454), and 85% (437) completed six platinum-based chemotherapy cycles, respectively. Paclitaxel dose intensification was achieved with weekly treatment (median total paclitaxel dose 1010 mg/m2 in group 1; 1233 mg/m2 in group 2; 1274 mg/m2 in group 3). By February, 2017, 1018 (65%) patients had experienced disease progression. No significant progression-free survival increase was observed with either weekly regimen (restricted mean survival time 24·4 months [97·5% CI 23·0-26·0] in group 1, 24·9 months [24·0-25·9] in group 2, 25·3 months [23·9-26·9] in group 3; median progression-free survival 17·7 months [IQR 10·6-not reached] in group 1, 20·8 months [11·9-59·0] in group 2, 21·0 months [12·0-54·0] in group 3; log-rank p=0·35 for group 2 vs group 1; group 3 vs 1 p=0·51). Although grade 3 or 4 toxic effects increased with weekly treatment, these effects were predominantly uncomplicated. Febrile neutropenia and sensory neuropathy incidences were similar across groups. INTERPRETATION: Weekly dose-dense chemotherapy can be delivered successfully as first-line treatment for epithelial ovarian cancer but does not significantly improve progression-free survival compared with standard 3-weekly chemotherapy in predominantly European populations. FUNDING: Cancer Research UK, Medical Research Council, Health Research Board in Ireland, Irish Cancer Society, Cancer Australia.

When RON MET TAM in Mesothelioma: All Druggable for One, and One Drug for All?

Malignant pleural mesothelioma (MPM) is an aggressive inflammatory cancer with a poor survival rate. Treatment options are limited at best and drug resistance is common. Thus, there is an urgent need to identify novel therapeutic targets in this disease in order to improve patient outcomes and survival times. MST1R (RON) is a trans-membrane receptor tyrosine kinase (RTK), which is part of the c-MET proto-oncogene family. The only ligand recognized to bind MST1R (RON) is Macrophage Stimulating 1 (MST1), also known as Macrophage Stimulating Protein (MSP) or Hepatocyte Growth Factor-Like Protein (HGFL). In this study, we demonstrate that the MST1-MST1R (RON) signaling axis is active in MPM. Targeting this pathway with a small molecule inhibitor, LCRF-0004, resulted in decreased proliferation with a concomitant increase in apoptosis. Cell cycle progression was also affected. Recombinant MST1 treatment was unable to overcome the effect of LCRF-0004 in terms of either proliferation or apoptosis. Subsequently, the effect of an additional small molecular inhibitor, BMS-777607 (which targets MST1R (RON), MET, Tyro3, and Axl) also resulted in a decreased proliferative capacity of MPM cells. In a cohort of MPM patient samples, high positivity for total MST1R by IHC was an independent predictor of favorable prognosis. Additionally, elevated expression levels of MST1 also correlated with better survival. This study also determined the efficacy of LCRF-0004 and BMS-777607 in xenograft MPM models. Both LCRF-0004 and BMS-777607 demonstrated significant anti-tumor efficacy in vitro, however BMS-777607 was far superior to LCRF-0004. The in vivo and in vitro data generated by this study indicates that a multi-TKI, targeting the MST1R/MET/TAM signaling pathways, may provide a more effective therapeutic strategy for the treatment of MPM as opposed to targeting MST1R alone.

eHealth-based intervention to increase physical activity levels in people with cancer: protocol of a feasibility trial in an Irish acute hospital setting.

INTRODUCTION: Exercise and physical activity (PA) are established and effective treatment options for various side effects of cancer treatments such as surgery, chemotherapy and radiotherapy. The advent of eHealth brings new opportunities to influence healthy behaviours, using interactive and novel approaches. Influencing PA behaviours in people with cancer presents a potential application of this. The aim of this study is to evaluate the feasibility and preliminary efficacy of an intervention, using eHealth, for increasing PA in cancer survivors. METHODS AND ANALYSIS: This will be a single-arm pre-post feasibility study. We aim to recruit a heterogeneous sample of 60 participants from cancer clinics in St. James's Hospital, Dublin, Ireland. Eligibility criteria will include patients who have completed chemotherapy and/or radiotherapy with curative intent between 3 and 36 months prior to enrolment. The intervention will include the delivery of a 12-week PA programme. The eHealth aspect of the intervention will involve the provision of a Fitbit activity tracker, which will be used in conjunction with specific PA goals remotely prescribed and monitored by a physiotherapist. Primary outcomes will be feasibility measures related to the study (recruitment capability, data collection procedures, adherence and compliance, evaluation of the resources to implement the study and evaluation of participant responses to the intervention). Secondary measures will evaluate preliminary efficacy of the intervention in terms of clinical outcomes (body composition, PA (objective and self-report), quality of life and aerobic capacity). Primary and secondary outcomes will be assessed at baseline (as appropriate), at conclusion of the intervention and at a 6-month follow-up. ETHICS AND DISSEMINATION: Ethical approval has been granted by the St. James's Hospital/AMNCH Joint Ethics Committee (2016/05/02). Results from this study will be submitted for publication in peer-reviewed journals, as well as for presentation and dissemination at conferences in the field of oncology and survivorship. TRIAL REGISTRATION: NCT03036436; Pre-results.

The use of eHealth to promote physical activity in cancer survivors: a systematic review.

PURPOSE: Achieving adequate levels of physical activity (PA) and avoiding sedentary behaviour are particularly important in cancer survivors. eHealth, which includes, but is not limited to, the delivery of health information through Internet and mobile technologies, is an emerging concept in healthcare which may present opportunities to improve PA in cancer survivors. The aim of this systematic review was to explore the effects of eHealth in the promotion of PA among cancer survivors. METHODS: Suitable articles were searched using PubMed, CINAHL, EMBASE, PsychInfo, Web of Science and SCOPUS databases using a combination of keywords and medical subject headings. Articles were included if they described an eHealth intervention designed to improve PA in cancer survivors. Two reviewers screened studies for inclusion. RESULTS: In total, 1065 articles were considered. Ten studies met eligibility criteria. A variety of platforms designed to increase PA were described in these studies: web application (app) (n = 5), web and mobile application (n = 2), mobile app (n = 1), website only (n = 1), e-mail based (n = 1). All studies measured PA using self-report outcome measures with the exception of one study which measured steps using a Fitbit. Meta-analysis was not performed because of variations in study design and interventions. All studies reported improvements in PA, with 8/10 studies reporting statistically significant changes. CONCLUSION: The use of eHealth to promote PA in cancer survivors is a relatively new concept, which is supported by the recent emergent evidence described in this review. eHealth shows promise as a means of promoting and increasing daily PA, but further high-quality, longer term studies are needed to establish the feasibility and effectiveness of eHealth platforms aimed at that goal.

The ExPeCT (Examining Exercise, Prostate Cancer and Circulating Tumour Cells) trial: study protocol for a randomised controlled trial.

BACKGROUND: Prostate cancer (PrCa) is the second most common cancer in Ireland. Many men present with locally advanced or metastatic cancer for whom curative surgery is inappropriate. Advanced cancer patients are encouraged to remain physically active and therefore there is a need to investigate how patients with metastatic disease tolerate physical activity programmes. Physical activity reduces levels of systemic inflammatory mediators and so an aerobic exercise intervention may represent an accessible and cost-effective means of ameliorating the pro-inflammatory effects of obesity and subsequently decrease poor cancer-specific outcomes in this patient population. This study will assess the feasibility and safety of introducing a structured aerobic exercise intervention to an advanced cancer population. This study will also examine if the evasion of immune editing by circulating tumour cells (CTCs) is an exercise-modifiable mechanism in obese men with prostate cancer. METHODS: This international multicentre prospective study will recruit men with metastatic prostate cancer. Participants will be recruited from centres in Dublin (Ireland) and London (UK). Participants will be divided into exposed and non-exposed groups based on body mass index (BMI) ≥ 25 kg/m2 and randomised to intervention and control groups. The exercise group will undertake a regular supervised aerobic exercise programme, whereas the control group will not. Exercise intensity will be prescribed based on a target heart rate monitored by a polar heart rate monitor. Blood samples will be taken at recruitment and at 3 and 6 months to examine the primary endpoint of platelet cloaking of CTCs. Participants will complete a detailed questionnaire to assess quality of life (QoL) and other parameters at each visit. DISCUSSION: The overall aim of the ExPeCT trial is to examine the relationship between PrCa, exercise, obesity, and systemic inflammation, and to improve the overall QoL in men with advanced disease. Results will inform future work in this area examining biological markers of prognosis in advanced prostate cancer. TRIAL REGISTRATION: Clinicaltrials.gov NLM identifier: NCT02453139 . Registered on 12 May 2015. This document contains excerpts from the ExPeCT trial protocol Version 1.5, 28 July 2016.

Tumour islet Foxp3+ T-cell infiltration predicts poor outcome in nonsmall cell lung cancer.

The impact of host immunity on outcome in nonsmall cell lung cancer (NSCLC) is controversial. We examined the relationship between lymphoid infiltration patterns in NSCLC and prognosis.Tumour- and stroma-infiltrating CD3(+), CD8(+) and forkhead box P3 (Foxp3)(+) T-lymphocytes were identified using immunohistochemistry and a novel image analysis algorithm to assess total, cytotoxic and regulatory T-lymphocyte counts, respectively, in 196 NSCLC cases. The median cell count was selected as a cut-point to define patient subgroups and the ratio of the corresponding tumour islet:stroma (TI/S) counts was determined.There was a positive association between overall survival and increased CD8(+) TI/S ratio (hazard ratio (HR) for death 0.44, p<0.001) but an inverse relationship between Foxp3(+) TI/S ratio and overall survival (HR 4.86, p<0.001). Patients with high CD8(+) islet (HR 0.48, p<0.001) and Foxp3(+) stromal (HR 0.23, p<0.001) counts had better survival, whereas high CD3(+) and CD8(+) stromal counts and high Foxp3(+) islet infiltration conferred a worse survival (HR 1.55, 2.19 and 3.14, respectively). By multivariate analysis, a high CD8(+) TI/S ratio conferred an improved survival (HR 0.48, p=0.002) but a high Foxp3(+) TI/S ratio was associated with worse survival (HR 3.91, p<0.001).Microlocalisation of infiltrating T-lymphocytes is a powerful predictor of outcome in resected NSCLC.

A novel serum microRNA panel to discriminate benign from malignant ovarian disease.

Ovarian cancer is the seventh most common cancer in women and the most frequent cause of gynaecological malignancy-related mortality in women. Currently, no standardized reliable screening test exists. MicroRNA profiling has allowed the identification of signatures associated with diagnosis, prognosis and response to treatment of human tumours. The aim of this study was to determine if a microRNA signature could distinguish between malignant and benign ovarian disease. A training set of 5 serous ovarian carcinomas and 5 benign serous cystadenomas were selected for the initial experiments. The validation set included 20 serous ovarian carcinomas and 20 benign serous cystadenomas. The serum/plasma focus microRNA Exiqon panel was used for the training set. For the validation set a pick and mix Exiqon panel, which focuses on microRNAs of interest was used. A panel of 4 microRNAs (let-7i-5p, miR-122, miR-152-5p and miR-25-3p) was significantly down regulated in cancer patients. These microRNAs target WNT signalling, AKT/mTOR and TLR-4/MyD88, which have previously been found to play a role in ovarian carcinogenesis and chemoresistance. let-7i-5p, miR-122, miR-152-5p and miR-25-3p could act as diagnostic biomarkers in ovarian cancer.

Patients over 65 years are assigned lower ECOG PS scores than younger patients, although objectively measured physical activity is no different.

OBJECTIVES: The Eastern Cooperative Group Performance Status (ECOG PS) is a widely used standard functional classification in oncology practice, the verbal descriptors of which refer to physical activity (PA). Little is known about the cut-off points of this scale and measured PA levels. This research investigated the relationship between PS assigned, objectively measured PA, and patient age. MATERIALS AND METHODS: One hundred ambulatory patients with treatment-naive cancer wore an accelerometer (RT3) for a mean (SD) of 5.6 (1.1) days before initial oncology evaluation and ECOG PS assignment. RESULTS: Seventy five participants (75%) were <65 years and 25 were ≥65 years. Eighty nine (89%) were assigned an ECOG PS of 0 or 1 and 11% a PS of 2 or 3. A weak but significant inverse association was found between objectively measured PA and PS (rho = -0.26, p = 0.01). Seventy one participants (80%) with a PS of 0 or 1 spent more than 50% of waking hours resting. Participants assigned a PS of 2-3 spent significantly more time resting than those assigned a PS of 0 (p = 0.01). Age ≥65 years was significantly related to PS assigned (p = 0.04), although the older cohort were no less sedentary than younger patients. CONCLUSION: PA levels were low, but PS scoring reflected relative PA levels and differentiated between patients of PS 0 and 2-3. Chronological age was not predictive of activity levels, but older patients were assigned lower PS scores. Incorporation of objective PA measures may merit further investigation especially in the geriatric oncology setting.