Silent theatre 2 – Sunday 3 November

6:50 pm-8:30 pm

Room: Hall 4


Programme session type(s): Silent theatre

Non-Attendance in Two-week wait and Urgent Colorectal Cancer Referrals
Speaker: Harpreet Sekhon Inderjit Singh
Affiliation: West Middlesex University Hospital, Isleworth, UK

Abstract:

Colorectal cancer (CRC) is the second commonest cause of cancer death in the UK, attributing to 10% of cancer mortality. Survival is dependent upon early detection. The Two-week-wait (2WW) referral pathway was implemented in the UK in July 2000 to reduce delays in diagnosis and decrease mortality associated with CRC. Non-attendance of these appointments has adverse clinical outcomes for patients. The reasons for non-attendance are not clearly understood with no quantitative research previously performed. This study aims to determine the association between Age, Sex, Ethnicity, Geographical location (postcode) and Socioeconomic status (SES) on non-attendance in 2WW and urgent CRC referrals.

Method

A retrospective analysis of a prospectively collated database of 2WW and urgent CRC referrals at our unit from January 2016 to December 2018 was performed. Variables regarding patient age, sex, attendance status, ethnicity (Census 2011), postcode, and socioeconomic status were recorded. Chi-squared, Spearman’s Rank and multivariate analyses were performed to determine the relationship between these variables and non-attendance. The White-British population was used as the control group.

Results

A total of 9,829 patients (49.45% male, 50.55% female, mean age 64.42 years) were analysed with an overall non-attendance rate of 12.31% (1,210/9,829). There was an increased non-attendance risk in 1) Younger populations (Age <55 years: OR=1.189 CI=1.049-1.349 p=0.0076); 2) Three ethnic cohorts: Asian Other (OR=0.6778 CI=0.5151-0.892 p=0.0067), Black Other (OR=0.3852 CI=0.2046-0.7255 p=0.0045) and Not Stated (OR= 0.8102 CI=0.2162-0.3321 p=0.011); 3) Six postcodes (p <0.05) of which non-attendees in TW3 also had a significant risk of social deprivation. There was no correlation between gender or SES and non-attendance. Multivariate analysis confirmed the association between age and non-attendance (p=0.0012).

Conclusion

This novel study has identified high-risk groups for non-attendance. Further qualitative research into high-risk groups needs to be performed to allow early detection and diagnosis of CRC and improve clinical and oncological outcomes.

TOPARP-B: A Phase II Randomised Trial of the Poly(ADP)-Ribose Polymerase (PARP) Inhibitor Olaparib for Metastatic Castration Resistant Prostate Cancers (mCRPC) with DNA Damage Repair (DDR) Alterations
Speaker: Nuria Porta
Affiliation: The Institute of Cancer Research, London, UK

Abstract:

We previously reported the antitumor activity of olaparib (400mg BID) against molecularly unselected mCRPC (TOPARP-A; Mateo et al NEJM 2015). We now report TOPARP-B, a phase-II trial for patients with mCRPC preselected for putatively pathogenic DDR alterations.

Method

Patients with mCRPC progressing after >1 taxane chemotherapy underwent targeted sequencing of tumour biopsies and were deemed eligible when alterations (germline or somatic; mono- or bi-allelic) in any DDR gene were detected. Patients were randomised 1:1 under a “pick-the-winner” design to 400mg or 300mg of olaparib BID, aiming to exclude <30% response rate (RR) in either arm. The primary endpoint RR was defined as radiological response (RECIST 1.1) and/or PSA50% fall and/or CTC count conversion (Cellsearch; ≥5 to <5), confirmed after 4-weeks. Analyses of RR per gene alteration subgroup was pre-planned. Secondary endpoints included radiographic progression-free survival (rPFS), tolerability.

Results

Overall, 98 patients (mean age 67.6y) were randomised, with 92 patients evaluable for the primary endpoint (70 RECIST-evaluable; 89 PSA50%-evaluable; 55 CTC-evaluable).  All had progressed on ADT; all were post-docetaxel; 90% post-abiraterone/enzalutamide, 38% post-cabazitaxel. Overall RR was 54% (95%CI 39-69%, meeting threshold for primary endpoint) in the 400mg cohort and 39% (95%CI 25-55%) in the 300mg cohort. With a median follow-up of 20.5 months (mo), the overall median rPFS (mrPFS) was 5.5 mo. Subgroup analyses per altered gene identified indicated RR for: BRCA1/2 of 83% (25/30; mrPFS 8.3mo); PALB2 57% (4/7; mrPFS 5.3mo); ATM 37% (7/19; mrPFS 5.6mo); CDK12 25% (5/20; mrPFS 2.9mo); others [ATRX, CHEK1, CHEK2, FANCA, FANCF, FANCG, FANCI, FANCM, RAD50, WRN] 20% (4/20; mrPFS 2.8mo). The highest PSA50% response rates were observed in the BRCA1/2 (23/30; 77%) and PALB2 (4/6; 67%) subgroups.

Conclusion

Olaparib has antitumor activity against heavily pre-treated mCRPC with DDR gene defects, with BRCA1/2 aberrant tumours being most sensitive but with confirmed responses in patients with other DDR alterations.

© 2019 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2019 ASCO Annual Meeting. All rights reserved.

Age differences in patient concerns after Breast Cancer. An analysis of UK Electronic Holistic Needs Assessment data
Speaker: Richard Simcock
Affiliation: Sussex Cancer Centre

Abstract:

Holistic Needs Assessment (HNA) is a key component of the Recovery Package endorsed by NHS England. Macmillan’s eHNA is completed electronically via touch screen tablet and information is then sent through a secure website to support care planning.
Anonymous eHNA data can be used to look at the overall needs of different groups of people. We present an analysis of the most prevalent concerns based on all eHNA data collected in 2018 from women with a breast cancer diagnosis stratified by age.

Method

Data collected via eHNA at any point in the cancer pathway from all UK geographies were available. All concerns were tabulated and the most frequently recorded are presented. Age was categorised into seven groups (18-30, 31-40, 41-50, 51-60, 61-70, 71-79, 80+)

Results

5468 eHNA records were available for analysis.
Due to the heterogeneity of data collection points, formal comparative statistical analysis was not appropriate and not performed.
85% of patients raised at least one concern, 75% at least 2 and 66% at least 3.
‘Worry, fear and anxiety’ and ‘Tired, exhausted or fatigued’ were consistently amongst the main concerns across all age groups. Worry was the most commonly raised concern in all age groups from 18-60 whilst fatigue was the most common in those over 60. ‘Thinking about the future’ featured as a common concern in all age cohorts before 70, but not after.

Conclusion

Our results highlight the use of eHNA to illustrate the chief concerns of women living with and beyond breast cancer. Worry and fatigue were the most commonly reported concerns for all age groups.
The analysis also highlights the utility of eHNA beyond individual care planning in providing descriptive data on a subset of the cancer population..

Role of cholesterol in colon cancer and its impact on AOM/DSS induced mouse intestinal tumourigenesis
Speaker: Shyamananda Singh Mayengbam
Affiliation: National Centre for Cell Science, Savitribai Phule Pune University, Pune, India

Abstract:

Clinical studies show a significant correlation in alteration of blood cholesterol level with colon cancer. Numerous studies have reported that blood cholesterol level often decreases in colon cancer patient, which is also negatively correlated with stage of tumour. We investigate the role of cholesterol in lipid and glucose metabolism of colon cancer along with various other signalling molecules.

Method

For understanding the role of cholesterol in colon cancer, long term colony formation, enzyme activity assay, glucose & lactate estimation were performed in HCT116 p53+/+ and p53-/- cells in the presence or absence of low density lipoprotein cholesterol (LDLc) and high density lipoprotein cholesterol (HDLc). Immunoblot and confocal microscopy for studying molecular events associated with cholesterol and colon cancer. C57BL/6J mice were used for in vivo isograft and chemically induced (AOM/DSS) colon cancer model.

Results

In vivo studies shows that mice fed on high cholesterol diet and high fat diet increases the incidence of AOM/DSS induced polyp formation, indicative of colon cancer when compared to mice fed with normal diet. Moreover, our in vitro result shows that, supplementation of LDLc and HDLc also increases colon cancer cell proliferation through ERK activation. We found that treatment of LDLc and HDLc increases glycolytic enzyme activities thereby enhancing glucose utilization and lactate production which in turns triggers the overexpression of monocarboxylate transporter 4 (MCT-4) for lactate efflux. Apart from increased enzyme activity, it also facilitates intracellular cholesterol accumulation and lipid droplet formation along with the up-regulation of LDL receptor (LDLR).

Conclusion

Both in vitro and in vivo results show a positive correlation of cholesterol with colon cancer cell proliferation and incidence. The role of cholesterol in lipid and glucose metabolism in colon cancer cells needs further investigation. Deciphering the underlying molecular mechanism of cholesterol associated events in colon cancer will help in better management of colon cancer.

18F-FDG-PET in Guided Dose-Painting with Intensity Modulated Radiotherapy in Oropharyngeal Tumours - Final Toxicity and Disease Outcomes of FiGaRO Phase I Multicentre Feasibility Study
Speaker: Delali Adjogatse
Affiliation: Dept of Oncology, Guy’s and St Thomas NHS Foundation Trust, London, UK

Abstract:

The FiGaRO trial assessed the feasibility and safety of delivering a PET-guided radiotherapy (RT) boost to the FDG-avid primary tumour, following 1 cycle of platinum-based induction chemotherapy, in patients with intermediate and high risk locally advanced oropharyngeal cancer.

Method

Patients underwent a planning 18FDG-PET-CT scan, immobilised in the treatment position, after one cycle of induction chemotherapy. The volume of persistent FDG-avidity in the primary tumour was escalated to 71.5Gy/30# (75.85Gy BED), delivered using a simultaneous integrated boost (SIB-IMRT) technique. The clinical radical (primary/nodal) and elective (nodal) volumes were treated to 65Gy/30# and 54Gy/30# respectively.  RT was delivered with concomitant platinum-based chemotherapy (following 2 cycles of induction chemotherapy). The primary outcome was incidence of radiation-induced mucosal ulceration at 12 months post-treatment, with an incidence of 10% or less deemed acceptable. Secondary outcomes included acute and other late toxicities and disease outcomes (NCICTCAEv.4.0, RTOG and LENTSOMA scales).

Results

Twenty-four patients were treated between 2014 and 2018, in 2 UK centres. Median follow-up was 36 months (range 4-56). Pre-defined planning target volume and organ at risk dose constraints were met in all cases. All patients completed treatment. There were no incidents of acute grade 4 toxicity. There were no cases of persistent mucosal ulceration at 12 months. RTOG grade 3 mucosal toxicity at 12 months was recorded in 1 patient (atrophy and telangiectasia). This patient had mucosal ulceration at 6 months which resolved by 12 months. One patient was feeding-tube dependent at 12 months, however mucosal integrity was intact. Local control was 83.3% (n=20), and loco-regional control was 79.2% (n=19). Overall survival at 1- and 3-years was 87.5% and 82.9% respectively. Disease-free survival was 83.3% at 1 year and 78.95% at 3 years.

Conclusion

PET-guided dose escalated chemo-radiotherapy, following induction chemotherapy, is feasible and associated with favourable mucosal toxicity rates.

Clinical Utility of Autoantibodies in Early Detection of Breast Cancer
Speaker: Daniyah Alfattani
Affiliation: CEAC group

Abstract:

Autoantibodies against numbers of tumour-associated antigens (TAAs) were shown to be relevant tumor biomarkers and can be detected up to 5 years before the tumour is overt clinically. Early diagnosis of cancer is paramount to improved survival by enabling treatment prior to cancer spreading, when tumours should be both surgically removable and curable. The NHS in Scotland is currently carrying out a RCT (ECLS) involving 12,000 individuals at high risk of developing lung cancer being randomised to having (or not) an autoantibody ELISA blood test (EarlyCDT-Lung®) – followed by CT scans over 2 years follow-up in those individuals with a positive test – for early lung cancer detection.

We are aiming to develop a blood test enabling the early detection of breast cancer to significantly improve clinical outcome.

Method

In this pilot study, 180 breast cancer matched control samples were screened for the presence of autoantibodies against 67 TAAs which have already been shown to involve in breast cancer pathology. Optimised Protein microarray technology was applied for this study.

Results

The results confirmed our hypothesis that BC induce autoantibodies (AAbs) against different panels of specific tumour associated antigens (TAAs) used in the pilot study. The assay provided cancer/control discrimination through detection of AAbs against TAAs.

Conclusion

We identified antigen panels of sufficient sensitivity and specificity for early detection of BC based upon serum profiling of autoantibody response. This opens the possibility of a blood test for screening and detection of breast cancer.

Assessment of the Outcome of Treating Spinal Oligometastases with Stereotactic Ablative Body Radiotherapy
Speaker: Helen Saxby
Affiliation: Charing Cross Hospital

Abstract:

Spinal metastases are common in patients with advanced cancer and can cause severe morbidity. Stereotactic ablative body radiotherapy (SABR) has been shown to be a safe and effective treatment of spinal metastases with a 90% local control rate [1].

The aim of this study was to assess the outcome of patients who had received SABR to spinal oligometastases at the Royal Surrey County Hospital (RSCH) under the Commissioning through Evaluation programme.

Method

Data were collected retrospectively from the institutional SABR database. All patients who received SABR to spinal oligometastases at the RSCH between 01.01.2016 and 01.01.2019 were included. Patients were treated using a TrueBeam linear accelerator.

Results

24 spinal metastases were treated in 18 patients. 12 patients had a single spinal metastasis treated and 6 patients had two spinal metastases treated. The median age of patients was 69 years (range 45 to 79 years).

Of the patients treated nine (50.0%) had a primary prostate cancer, four (22.2%) had a primary breast cancer, three (16.7%) had a primary renal cancer, one (5.6%) had a primary lung cancer and one (5.6%) had a primary thyroid cancer. Of the 24 spinal metastases treated 3 (12.5%) were cervical, 13 (54.2%) thoracic and 8 (33.3%) lumbar.

The median length of follow up was 1.5 years (range 6 months to 3.5 years). All patients are currently alive and none experienced grade three or four toxicity following treatment. There was a 100% local control rate of the spinal metastases. Seven patients (38.9%) experienced distant relapse of their disease.

Conclusion

This study has shown SABR to be a safe and effective treatment for spinal oligometastases. There was an excellent (100%) local control rate of spinal oligometastases from multiple primary tumour sites using SABR.

An investigation of eating problems in people with stage I-III colorectal cancer receiving Systemic Anti-Cancer Therapy (SACT): the potential for nutritional care to potentiate cancer treatment
Speaker: Jane Hopkinson
Affiliation: Cardiff University

Abstract:

Eating problems during cancer treatment are common and often self-managed. Support for optimal nutritional intake is important, as malnutrition is associated with poor treatment tolerance, less intense treatment, poor quality of life and morbidity. Research has found many people with cancer are dissatisfied with their nutritional care during treatment. We investigated eating problems in people with colorectal cancer (CRC) receiving SACT to identify factors that can reduce the risk of malnutrition and improve people’s experience. Thus maximising chances of completing/tolerating treatment and better overall associated outcomes.

 

Method

A self-complete questionnaire, including a scored Patient-Generated Subjective Global Assessment (PG-SGA) short form, was administered to 60 adults with CRC attending an outpatient cancer clinic to assess eating problems and malnutrition risk (recruitment on-going). Semi-structured telephone interviews were conducted with a maximum variation sub-sample of patients who completed the questionnaire (n=17), to explore what facilitates optimal nutritional intake and self-care.

Results

A high proportion of survey respondents (77%) reported changes in their eating habits. Just over half (57%) reported eating less; 42% reported weight loss, but less than one in four with either change reported related concern. However, 60% of the PG-SGA short form scores indicated need for nutritional intervention, demonstrating discordance between respondents’ weight/eating concern and nutritional risk. Analyses of the interview data reveals weight and eating can be emotive and advice conflicting for people. Factors which influence self-management of eating difficulties include: prior nutritional knowledge, maintaining or lack of routine, habitual eating, information overload, internet information and family support/pressure.

Conclusion

We found a majority of people with stage I-III colorectal cancer experienced eating problems and were at nutritional risk. Yet, a minority had awareness of this risk or felt concerned about changes in eating/weight. This paper discusses the potential for psychoeducation to activate self-management of risk and the implications for treatment tolerance and outcomes.

Repurposing of niclosamide (a putative STAT3 inhibitor) to potentiate chemotherapeutic drugs in treating colorectal cancer
Speaker: Mia Mingxia Wu
Affiliation: The Chinese University of Hong Kong

Abstract:

Chemotherapy remains the first-line treatment option for colorectal cancer (CRC) patients. However, aberrant cell signaling regulation leads to poor drug response. Signal transducer and activator of transcription protein 3 (STAT3) is an important signaling molecule driving cancer cell survival. Its overexpression is associated with poor prognosis in CRC patients. This study aimed to repurpose approved drugs with putative STAT3 inhibitory effect to potentiate chemotherapeutic drugs for CRC treatment.

Method

The combinations of four putative STAT3 inhibitors (niclosamide, nifuroxazide, C118-9, SH-4-54) and three chemotherapeutic drugs (5-fluorouracil, SN38 and oxaliplatin) were evaluated in five human CRC cell lines harboring different genetic abnormalities (HCT116, HT29, HCC2998, LoVo, SW480). Antiproliferative effect was assessed by the sulforhodamine B assay. Median effect analysis was performed to identify the synergistic drug combinations. Flow cytometric assays were used to detect apoptosis and cell cycle regulation. Inhibition of STAT3 and its downstream targets were examined by Western blot analysis. The effect of drug combinations on DNA damage was also investigated.

Results

The combination of SN38 and niclosamide was found to be the most synergistic in multiple CRC cell lines. Interestingly, sequential treatment with SN38 preceding niclosamide gave rise to more synergistic antiproliferative and apoptotic effect. The combination was also shown to produce the most remarkable enhancement in G2/M cell cycle arrest. Compared with individual treatment alone, the SN38-niclosamide combination was shown to cause more remarkable STAT3 inhibition and down-regulation of the cell cycle regulators Cyclin-D1 and Cyclin-B. Moreover, niclosamide was also found to prevent SN38-induced STAT3 up-regulation and enhance DNA damage.

Conclusion

Niclosamide may be repurposed to potentiate other chemotherapeutic drugs for treating CRC. The beneficial combinations were found to be schedule-dependent, as exemplified by the most synergistic effect from SN38-preceding-niclosamide combination. STAT3 inhibition and enhanced induction of DNA damage in cancer cells contribute to the efficacious combination.

Repurposing loperamide to overcome gefitinib resistance by triggering apoptosis independent of autophagy induction in KRAS mutant NSCLC cells
Speaker: Christy Wing Sum Tong
Affiliation: The Chinese University of Hong Kong

Abstract:

The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, gefitinib, provides significant clinical benefit for non-small cell lung cancer (NSCLC) patients with activating EGFR mutations. However, primary resistance remains a major obstacle to effective gefitinib therapy in patients with activating KRAS mutations. Autophagy induction was reported to promote autophagic cell death in RAS-driven cancer cells. Therefore, we investigated the combination of gefitinib and autophagy inducers to circumvent drug resistance in KRAS-mutated NSCLC cells.

Method

NSCLC cell lines harboring KRAS mutation (A549 and H460) and EGFR mutation (H1975 and H1650) were employed. Quantitative real-time PCR and Western blot analysis were used to examine the expression of autophagy-related genes and proteins, respectively. Sulforhodamine B assay was employed to evaluate the cytotoxicity of drug combinations. Annexin-V/propidium iodide apoptosis assay was used to investigate the apoptotic effect after the treatment.

Results

Loperamide, commonly used to relieve the dose-limiting adverse effect of diarrhea from gefitinib, was found to induce autophagy by increasing autophagy-related genes, ATG2B and RGS1, and an autophagy-related protein, LC3-II. Combination treatment of gefitinib and loperamide produced synergistic cytotoxic effect only in KRAS-mutated cell lines (A549 and H460) with combination indexes of 0.37 ± 0.04 and 0.68 ± 0.10, respectively. Knocking down Atg5 did not reverse the synergistic cytotoxic effect, suggesting that autophagy induction did not directly cause cancer cell death. However, this drug combination produced a remarkable synergistic apoptotic effect. Inhibition of autophagy induction either chemically (by 3-methyladenine) or genetically (by Atg5 silencing) did not reverse the synergistic apoptotic effect, indicating that the apoptotic cell death was not mediated by autophagy induction.

Conclusion

Our results indicated that loperamide could be repurposed to combine with gefitinib to produce synergistic anti-cancer effect in KRAS mutant NSCLC cell lines by further inducing synergistic apoptosis, which is independent of autophagy induction.

Nr4a1-loss causes an acceleration of Myc-driven lymphomagenesis and an induction of gene of the B7-CD28
Speaker: Alexander Deutsch
Affiliation: Medical University of Graz, Graz, Austria

Abstract:

In aggressive lymphomas, low expression of NR4A1 is associated with poor cancer-specific survival and its overexpression suppresses lymphoma cell growth indicating its tumor suppressor properties.

Method

To comprehensively study the function of Nr4a1-loss in lymphomagenesis, we intercrossed the EµMyc lymphoma-mouse with the Nr4a1-/- mouse. Furthermore, we transplanted lymphoma cells of EµMycNr4a1-/- and EµMycNr4a1+/+ mice into immune-competent C57BL/6 mice and immune-deficient Fox-Chase-SCID beige mice. Finally, we determined the expression levels of the immune regulatory genes by RQ-PCR in our DLBCL patient cohort.

Results

Loss of Nr4a1 in the EµMyc lymphoma model significantly accelerated lymphomagenesis. RNA-Seq data revealed upregulation of immune regulator genes of the B7-CD28 family in EµMyc-Nr4a1-/- lymphomas. Transplanting lymphoma cells with or without Nr4a1-loss into immune-competent mice led to accelerated lymphoma-development and a decreased survival in the absence of Nr4a1 and to no differences in immune-incompetent mice, indicating that the loss of Nr4a1 results in a suppression of anti-lymphoma immune response. Gene expression analysis of primary and engrafted lymphomas revealed that Nr4a1 is specifically implicated in the regulation of Pd1-Pdl1-Pdl2 and Ctla4-CD80-CD86 axis. Furthermore, flow cytometry analyses demonstrated that tumors transplanted from EµMycNr4a1-/- mice exhibited a significantly higher percentage of infiltrating T cells. Interestingly, the infiltrating CD8+ T cells displayed higher expressed Pd1 on their surface in transplanted tumors derived from EµMycNr4a1-/- mice, whereas Ctla-4 has not been investigated so far. In the human setting, we detected a significant negative association of NR4A1 expression levels and the PD1- PDL1- PDL2- and CTLA4- CD80CD86 in DLBCL confirming our mouse data.

Conclusion

Our data suggest that the tumor suppressive function of Nr4a1 is mediated by the regulation of Pd1Pdl1Pdl2 and Ctla4Cd80Cd86 axis in aggressive lymphomas. Thereby, it seems that Nr4a1 loss significantly contributes to the immune evasion of aggressive lymphomas and that it might act as a potential target for anti-lymphoma therapy.

The association between palliative healthcare service provision and place of death: a population study of cancer patients
Speaker: Maria Kelly
Affiliation: National Cancer Registry Ireland

Abstract:

Factors affecting where a patient dies are not limited to patient sociodemographic and clinical factors, but also characteristics of the health service where they receive care. There is a lack of empirical studies that systematically assess the influence of palliative healthcare service provision on place of death.

Method

We profiled cancer patients receiving specialist palliative care (SPC) with an analysis of place of death (PoD) using linked population data.  Incident invasive cancer, excluding non-melanoma skin cancer, in patients diagnosed from 1994-2016 in Ireland, who attended a cancer centre in 2016 and who died in 2016 were included. Patients were categorised based on having an indicator of an ‘SPC encounter’ or not in their hospital episode data. Patients were classified to one of eight geographical health regions based on their address at diagnosis. PoD was categorised from death certificates to ‘Home’, ‘Hospital’, ‘Hospice’, ‘Other’ and ‘Unknown’.   Descriptive statistics and logistic regression analyisis was used to examine factors associated with receiving SPC and PoD.

Results

We identified n=4139 cancer decedents for this study; 63% (n=2597) had an SPC encounter.  

Being younger, not married and from more deprived areas showed higher odds of an SPC encounter. After accounting for sociodemographic factors and relative to the most populous Eastern region, decedents in the Midland and the South Eastern regions were less likely to receive SPC, both regions with no SPC bed capacity.

Having an SPC encounter affected PoD; 43% of SPC recipients died in hospital versus 48% of non-recipients, 32% died in a hospice versus 16% while 18% died at home versus 28%.  SPC bed capacity by region contributed to the PoD variation.

Conclusion

A lack of regional inpatient hospice services impacts PoD in cancer patients who have had an SPC encounter in acute hospitals. This has implications for service commissioning and planning.

Top Ten Research Priorities in Cancer Early Detection: a priority setting partnership between patients and healthcare professionals
Speaker: Ellena Badrick
Affiliation: University of Manchester

Abstract:

There is a need for a rapid push forward in patient-relevant research in cancer early detection (ED) to reduce population-level cancer mortality. Current research might not address questions that need urgent answers for patients and healthcare professionals. A Detecting Cancer Early Priority Setting Partnership (PSP) was established to identify the top research priorities in cancer ED.

Method

Using a modified nominal group methodology established by the James Lind Alliance(JLA), patients, carers and healthcare professionals are surveyed to identify within-scope unanswered research questions relating to cancer ED, which are subsequently shortlisted through further surveys and stakeholder meetings. The shortlisted questions are discussed at a workshop and prioritised into a Top 10.  We established networks of national  and international stakeholders as participants, and linked with CRUK ICED Alliance centres.

The principals of a JLA PSP are: transparency of process; balanced inclusion of patient, carer and clinician perspectives; exclusion of non-clinician researchers from voting; exclusion of groups or organisations that have significant competing interests; and maintained audit trail from original submitted uncertainties to final prioritised list.

Results

We had 514 respondents, including 198 patients and carers, provided 1058 suggestions. These were checked against existing research and duplicates removed, 54 unique unanswered (indicative) research questions were identified as a result.

Between June and July 2019 an online survey will prioritise the long list of questions and approximately 30 of these will be taken forward to a consensus meeting on 4th September 2019.

The final Top 10 list of priorities will be first reported in the UK at the NCRI conference.

Conclusion

The findings of this PSP will be highly informative for determining the ED research agenda. This informs researchers and research funders about priorities so that they can make their research as meaningful as possible to the people who need it.

Antiproliferation and anti-invasion of 1’-Acetoxychavicol acetate on hormonal-resistant breast cancer cells
Speaker: Nalinee Pradubyat
Affiliation: University of Liverpool

Abstract:

Although ER-positive breast cancer patients have a good prognosis, 30-50% of patients will experience recurrence due to the development of resistance. Cancer cells develop resistance through various signalling pathways including, NFkB pathway. NFkB activation was initially associated with the aetiology and progression of hormone-independent BC. Treatment options for hormonal-resistant breast cancers are limited. Here we exploited the cytotoxicity, antiproliferation and anti-invasion effects of 1’ acetoxychavicol acetate (ACA) on downstream cancer-promoting NFkB regulated genes and proteins (such as CCND1, C-myc, CXCR4, and uPA) on tamoxifen-resistant (MCF7/LCC2) and tamoxifen/fluvestrant-resistant (MCF7/LCC9) breast cancer cells.

Method

Cytotoxicity of ACA was explored in vitro using MTT assays at three different incubation time; 24 h, 48 h, and 72 h. Anti-invasion of ACA was done by Matrigel invasion assay, while the mode of action was elucidated through real-time PCR followed by western blotting analysis.

Results

We showed that ACA significantly inhibited the growth of MCF7, MCF7/LCC2, and MCF7/LCC9 in a dose- and time-dependent manner. We also found that ACA suppressed MCF7/LCC2 and MCF7/LCC9 cells invasion. The effects correlated with downregulation of the proteins involved in cell proliferation (ERK1/2, PI3K/AKT) and invasion (uPA) as well as downregulation of cancer-promoting NFkB regulated genes including, proliferative (CCND1, C-myc), invasive (CXCR4, uPA) biomarkers.

Conclusion

Overall, our findings suggest that ACA exhibits antiproliferative effect through abrogation of ERK1/2, PI3K/AKT, which affect the transcriptional level of CCND1and C-myc while the anti-invasive effect of ACA targets CXCR4 and uPA.

Tumour Deposits as an independent prognostic factor for Colorectal Cancer
Speaker: Jinpo Xiang
Affiliation: Imperial College London

Abstract:

It is known that the presence of tumour deposits (TD) is a prognostic indicator for Colorectal cancer patients, although there is limited research into the extent which tumour deposits can be relied upon as a prognostic indicator in patients with Lymph Node metastasis. Current staging systems acknowledge the presence of tumour deposits only in the absence of lymph node metastasis.  Further analysis of patient outcomes based on the newest TD definitions as published in the 8th edition TNM Classification (published 2017) is required, to assess the impact that tumour deposits has, independent of lymph node metastasis. The aim of this study is to investigate the significance of TD as an independent prognostic factor. Investigate the clinicopathological factors associated with incidence of TD and assess the Recurrence Free Survival of colorectal cancer patients that have TD.

Method

A single centre study comprising 233 patients with stage II/III colorectal cancer (all underwent surgical resection between January 2009 and December 2011) were assessed for TD and lymph node metastasis using histopathology slides stained with Haemotoxylin and Eosin. The TD status is compared against their recurrence free survival (RFS), obtained from regular follow-up appointments after surgery.

Results

25% of patients had positive TD status. Left sided and rectal tumours, lymphatic invasion and lymph node metastasis were associated with TD incidence. RFS for both stage II and III patients with TD positive status were significantly lower than the same staging groups without TD negative status. Patients with TD presence had significantly worse RFS irrespective of any lymph node metastasis.

Conclusion

Tumour deposits are a significant prognostic indicator for patients with stage II/III colorectal cancer, independent of lymph node metastasis. The ability of tumour deposits to separate the two groups of mixed stage II and III patients exhibits that in this study, the tumour deposit status of the patients may have provided more accurate prognostic information than lymph node metastasis. Based on these results, we propose revision of the AJCC TNM staging system to include documentation of TD as part of cancer staging, even in the presence of lymph node metastasis.