Irish Cancer Society Research Articles

Trimodality therapy versus perioperative chemotherapy in the management of locally advanced adenocarcinoma of the oesophagus and oesophagogastric junction (Neo-AEGIS): an open-label, randomised, phase 3 trial

The optimum curative approach to adenocarcinoma of the oesophagus and oesophagogastric junction is unknown. We aimed to compare trimodality therapy (preoperative radiotherapy with carboplatin plus paclitaxel [CROSS regimen]) with optimum contemporaneous perioperative chemotherapy regimens (epirubicin plus cisplatin or oxaliplatin plus fluorouracil or capecitabine [a modified MAGIC regimen] before 2018 and fluorouracil, leucovorin, oxaliplatin, and docetaxel [FLOT] subsequently). Neo-AEGIS (CTRIAL-IE 10-14) was an open-label, randomised, phase 3 trial done at 24 centres in Europe. Patients aged 18 years or older with clinical tumour stage T2-3, nodal stage N0-3, and M0 adenocarcinoma of the oesophagus and oesophagogastric junction were randomly assigned to perioperative chemotherapy (three preoperative and three postoperative 3-week cycles of intravenous 50 mg/m2 epirubicin on day 1 plus intravenous 60 mg/m2 cisplatin or intravenous 130 mg/m2 oxaliplatin on day 1 plus continuous infusion of 200 mg/m2 fluorouracil daily or oral 625 mg/m2 capecitabine twice daily up to 2018, with four preoperative and four postoperative 2-week cycles of 2600 mg/m2 fluorouracil, 85 mg/m2 oxaliplatin, 200 mg/m2 leucovorin, and 50 mg/m2 docetaxel intravenously on day 1 as an option from 2018) or trimodality therapy (41·4 Gy in 23 fractions on days 1-5, 8-12, 15-19, 22-26, and 29-31 with intravenous area under the curve 2 mg/mL per min carboplatin plus intravenous 50 mg/m2 paclitaxel on days 1, 8, 15, 22, and 29). The primary endpoint was overall survival, assessed in all randomly assigned patients who received at least one dose of study drug, regardless of which study drug they received, by intention to treat. Secondary endpoints were disease-free survival, site of treatment failure, operative complications, toxicity, pathological response (complete [ypT0N0] and major [tumour regression grade 1 and 2]), margin-free resection (R0), and health-related quality of life. Toxicity and safety data were analysed in the safety population, defined as patients who took at least one dose of study drug, according to treatment actually received. The initial power calculation was based on superiority of trimodality therapy (n=366 patients); it was adjusted after FLOT became an option to a non-inferiority design with a margin of 5% for perioperative chemotherapy (n=540). This study is registered with ClinicalTrials.gov, NCT01726452. Between Jan 24, 2013, and Dec 23, 2020, 377 patients were randomly assigned, of whom 362 were included in the intention-to treat population (327 [90%] male and 360 [99%] White): 184 in the perioperative chemotherapy group and 178 in the trimodality therapy group. The trial closed prematurely in December, 2020, after the second interim futility analysis (143 deaths), on the basis of similar survival metrics and the impact of the COVID-19 pandemic. At a median follow-up of 38·8 months (IQR 16·3-55·1), median overall survival was 48·0 months (95% CI 33·6-64·8) in the perioperative chemotherapy group and 49·2 months (34·8-74·4) in the trimodality therapy group (3-year overall survival 55% [95% CI 47-62] vs 57% [49-64]; hazard ratio 1·03 [95% CI 0·77-1·38]; log-rank p=0·82). Median disease-free survival was 32·4 months (95% CI 22·8-64·8) in the perioperative chemotherapy group and 24·0 months (18·0-40·8) in the trimodality therapy group [hazard ratio 0·89 [95% CI 0·68-1·17]; log-rank p=0·41). The pattern of recurrence, locoregional or systemic, was not significantly different (odds ratio 1·35 [95% CI 0·63-2·91], p=0·44). Pathological complete response (odds ratio 0·33 [95% CI 0·14-0·81], p=0·012), major pathological response (0·21 [0·12-0·38], p<0·0001), and R0 rates (0·21 [0·08-0·53], p=0·0003) favoured trimodality therapy. The most common grade 3-4 adverse event was neutropenia (49 [27%] of 183 patients in the perioperative chemotherapy group vs 11 [6%] of 178 patients in the trimodality therapy group), followed by diarrhoea (20 [11%] vs none), and pulmonary embolism (ten [5%] vs nine [5%]). One (1%) patient in the perioperative chemotherapy group and three (2%) patients in the trimodality therapy group died from serious adverse events, two (one in each group) of which were possibly related to treatment. No differences were seen in operative mortality (five [3%] deaths in the perioperative chemotherapy group vs four [2%] in the trimodality therapy group), major morbidity, or in global health status at 1 and 3 years. Although underpowered and incomplete, Neo-AEGIS provides the largest comprehensive randomised dataset for patients with adenocarcinoma of the oesophagus and oesophagogastric junction treated with perioperative chemotherapy (predominantly the modified MAGIC regimen), and CROSS trimodality therapy, and reports similar 3-year survival and no major differences in operative and health-related quality of life outcomes. We suggest that these data support continued clinical equipoise. Health Research Board, Cancer Research UK, Irish Cancer Society, Oesophageal Cancer Fund, and French National Cancer Institute.

Evaluation of community outreach feasibility programmes on improving cancer-related, preventive, health behaviour

BackgroundThe COVID-19 pandemic had a negative impact on cancer services and will have likely led to delayed early detection and diagnosis. In response, the Irish Cancer Society (ICS) planned and delivered seven cancer roadshow events run on 15 days across seven shopping centres in four deprived areas based on Trinity National Deprivation Index, 2016, in Limerick, Cork, Waterford and Dublin regions in Ireland to educate and promote awareness about cancer signs and symptoms, importance of screening, positive lifestyle changes, and encourage medical care-seeking behaviour. MethodsICS nurses and trained ICS volunteers conducted health checks such as blood pressure, BMI, and CO2, monitoring (one health check per person maximum), provided health information and conducted motivational interviews in aforementioned regions. Data were collected via an anonymous questionnaire from participants and volunteers. SPSS was used for descriptive and pre–post event comparative analysis. Findings98 people, all adults (54 men and 44 women) participated; 88% (n=86) found the information provided useful, 85% (n=83) approved of the health check and 73% (n=71) stated that they would probably make changes to their current lifestyle to reduce their cancer risk. Moderate or high understanding of cancer signs and symptoms (from 62% to 82%; p<0·0001) and moderate or high awareness of cancer risk factors (from 49% to 61%; p<0·0001) both rose after the events. If symptomatic for cancer, 78% (n=76) of participants would probably visit their general practitioner and 74% (n=72) would probably contact ICS. Younger people (aged ≤40 years) were more likely to consider consulting a health-care professional if symptomatic (p=0·0270) and to contact the ICS (p=0·0070) for more information. High numbers of participants (99%; n=97) and volunteers (95%; n=42) recommended a nationwide roll out. InterpretationWith moderate to high levels of public engagement, volunteers reported people discussed cancer screening, information on making lifestyle changes, and ICS services. Such community outreach programmes to promote cancer-related health are feasible and acceptable and might lead to improved knowledge of cancer prevention, early detection, and improved intention to seek help for health concerns. Determination of effectiveness in preventive behaviour, early diagnosis, and cost effectiveness would require longer term follow up. FundingIrish Cancer Society.

Impact of community outreach programme on improving cancer related preventive health behaviour

Abstract   Cancer services were negatively affected due to the Covid-19 pandemic and will have likely delayed early detection and diagnosis. The Irish Cancer Society (ICS) planned and delivered a number of cancer roadshow events in 4 deprived regions in Ireland to address improvements in awareness of cancer signs, importance of screening, positive lifestyle changes and encourage medical care-seeking behaviour. Health checks (blood pressure, BMI &amp; CO2 monitoring) and motivational interviews were carried out by ICS nurses and trained ICS volunteers. Data was collected via anonymous questionnaire from participants and volunteers. SPSS was used for analysis. 98 people (54 male, 44 female) participated; 87.7% found the information provided useful, 84.7% approved of the health check and 72.5% stated that they would likely make changes to their current lifestyle to reduce their cancer risk. Moderate/high understanding of cancer signs and symptoms and moderate/high awareness of cancer risk factors both rose post event (from 62.2% to 81.6% (p &amp;lt; 0.001) and from 49% to 61.2% (p &amp;lt; 0.001) respectively). If symptomatic for cancer 77.6% of participants would likely visit their GP and 73.5% would likely contact ICS. Younger people (aged ≤40 years) were more likely to consider consulting a healthcare professional if symptomatic (p = 0.027) and to contact the ICS (p = 0.007) for more information. High numbers of participants (98.9%) and volunteers (95.2%) recommended a nationwide roll out. Volunteers reported moderate/high levels of public engagement; the most common topics discussed were own treatment experience, cancer screening, information on making lifestyle changes and ICS services. Volunteers reported the need for more training and improvements to some organisational aspects. More rigorous cancer health promotion programmes are required to counter disrupted cancer services. Our results suggest such cancer roadshow events are both feasible and beneficial at this time post pandemic. Key messages • Health literacy is continuous process to achieve positive health outcomes. • Reaching out to people in different setting is acceptable and potentially effective.

Examining the Usefulness of the Charlson Comorbidity Index to Predict Early Mortality in Patients with Acute Myeloid Leukaemia

Background and aims: Acute myeloid leukaemia (AML) is a relatively rare haematological malignancy which is the most common acute leukaemia in adults. Patients with AML often have a substantial comorbidity burden. Consequently, different scores are used in clinical practice to predict outcomes in patients with multiple comorbidities. The Charlson Comorbidity Index (CCI), calculated based on 19 different medical conditions, weighs the comorbidities to measure a patient's burden of disease. Previous publications have suggested that the CCI may be useful in determining survival in AML patients. However, the CCI is not in routine use in Ireland for assessing patients with AML. In this study we examined the usefulness of the CCI to predict early mortality in AML patients, drawing on data from the Extended Blood Cancer Registration (EBCR) in Ireland.Methods: The EBCR was undertaken by National Cancer Registry Ireland registrars trained by consultant haematologists and deployed in national centres. Data collection began in 2017 and continued to 2019; 141 AML patients underwent extended data registration. Comorbidities were identified by ICD-9 codes and chart review. Kaplan Meier curves and Cox regression analyses were used to determine the usefulness of the CCI to predict early mortality in AML patients.Results: Of the 141 AML patients, 82% were between 50 and 70 years of age and 84 had died by 31/12/2019 (median survival time = 289.0 days). The median survival time for patients in the lowest tertile of the CCI was 498.5 days, compared to 246.0 and 116.5 days for subjects in tertiles 2 and 3, respectively (Figure 1. Log rank P-value <.001). In Cox regression analysis, a dose-response relationship was observed, with patients in the highest CCI tertile displaying a greater risk (HR = 4.90, 95% CI: 2.79-8.63) of mortality compared to subjects in tertile 2 (HR = 2.74, 95% CI: 1.64-4.57) and tertile 1 (reference). However, this relationship was attenuated, and non-significant, in analyses which adjusted for age at diagnosis and in a further multivariable model.Conclusions: Although results demonstrate a strong relationship between the CCI and early mortality in AML patients, our findings suggest that the CCI provides little or no additional prognostic information beyond that which is obtained from age at AML diagnosis alone. This study highlights the importance of validating risk assessment tools in order to determine their potential usefulness in a clinical setting and emphasise the importance of weighing in the treatment decision making paradigm.The Blood Cancer Network Ireland (BCNI) thank the Science Foundation of Ireland (SFI) and the Irish Cancer Society (ICS) for funding (2015-2021).We also thank our colleagues in the National Cancer Registry Ireland for assistance, advice and guidance. [Display omitted] DisclosuresQuinn: Takeda: Honoraria. O'Dwyer: Bristol Myers Squibb: Research Funding; Janssen: Consultancy; ONK Therapeutics: Current Employment, Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees. Szegezdi: ONK Therapeutics: Research Funding.

The knowledge exchange and dissemination plan of the We Can Quit2 community-based stop-smoking trial

Abstract Background We Can Quit2 was a community-based randomised controlled trial which determined the feasibility and acceptability of We Can Quit (WCQ), a peer delivered stop-smoking programme comprising group support and free Nicotine Replacement Therapy (NRT) tailored to women living in socioeconomically disadvantaged areas in Ireland. Reengagement with key stakeholders took place as part of the trial Knowledge Exchange and Dissemination plan, to discuss strategies to optimise community engagement, recruitment and retention in a future definitive trial (DT), and the policy priorities arising from the trial. Methods Community stakeholders involved in trial recruitment and planning, Irish Cancer Society and Health Service Executive representatives were invited to an online interactive workshop in November 2020. Key trial findings were presented. Workshop discussion (field notes) and responses to a post-event anonymous questionnaire informed a list of challenges and suggestions for a future DT and policy development from a community perspective. Results Forty-one stakeholders attended the workshop, six completed the questionnaire. Dedicated additional time for community engagement and use of social prescribing as a recruitment tool were recommended. Greater adaptation of trial data and assistance to complete forms were suggested to address low literacy, which was a barrier to recruitment and retention. An intervention boost after WCQ delivery and encouragement of women to join other healthy community programmes to maintain their group, were recommended to facilitate retention and enhance sustainability. Policy priorities were to remove cost and administrative barriers to access NRT and ongoing provision of cessation services tailored to disadvantaged groups. Conclusions Important strategies to optimise design of a DT of WCQ effectiveness were recommended. Lessons learned may be relevant to other community-based health interventions in socioeconomically disadvantaged areas. Key messages The workshop provided a suitable forum for engagement of community and statutory stakeholders. Knowledge exchange activities facilitated an enhanced research design from a community perspective.

Selected Indices Of Physical And Psychological Health Of Lung Cancer Patients Scheduled For Surgery

PURPOSE: Lung cancer surgery offers a curative option but can result in complications. Low physical fitness levels increase the risk of surgical complications. Measuring physical fitness can better risk stratify patients and hence improve patient care. This study aims to investigate cardiorespiratory fitness, strength, physical activity and quality of life in individuals scheduled for lung cancer surgery. METHODS: Recruitment occurred at the patient’s pre-surgical clinic visit. Patients performed a 6-minute walk test (6MWT) to measure cardiorespiratory fitness, 30-second sit-to-stand test (30STS) to assess lower-limb strength and an upper-body grip strength test. The EuroQOL-EQ5D assessed quality of life on a scale from 0, worst health imaginable, to 100, best health imaginable. Step count was recorded by an ActivPAL micro 3 accelerometer (PAL Technologies, Glasgow, Scotland). The International Physical Activity Questionnaire-Short Form assessed self-reported time spent sitting, walking and completing moderate to vigorous intensity physical activity (MVPA). RESULTS: Twenty-two participants were recruited (54.5% male, mean 65 years). Average distance covered during a 6 MWT was 388.1 ± 75.0 m. Mean 30STS repetitions completed was 12.9 ± 2.9. Mean grip strength was 24.5 ± 9.2 kg. The mean EuroQOL-EQ5D score was 73.9 ± 12.9. Mean weekly step count was 45099.4 ± 19989.9 (n = 13). Participant’s reported sitting for an average of 6.1 ± 3.2 hours per day, 184.8 ± 131.2 minutes per week walking and 20.6 ± 41.6 minutes of MVPA per week. CONCLUSIONS: A 6 MWT <400 m is associated with an increased risk of complications within the first 30 days post-surgery. The mean 6 MWT distance in this study was 388.1 m. Research has reported similar pre-surgical 30STS results (12.6 ± 3.3) but higher grip strength (36.75 ± 10.15 kg) in lung cancer patients. This study found participants didn’t meet the the recommended exercise guidelines for cancer survivors. Therefore, interventions to support individuals with lung cancer to increase their activity are required to optimise patient care. This research is part of a larger randomised control trial which aims to identify the optimal peri-surgical exercise intervention and its effects on lung cancer patient’s physical, clinical and psychological health. Funded by the Irish Cancer Society.

What GDPR and the Health Research Regulations (HRRs) mean for Ireland: a research perspective

BackgroundIrish Health Research Regulations (HRRs) were introduced following the European Union (EU) General Data Protection Regulation (GDPR) in 2018. The HRRs described specific supplementary regulatory requirements for research regarding governance, processes and procedure that impact on several facets of research. The numerous problems that the HRRs and particularly “explicit consent” inadvertently created were presented under the auspices of the Irish Academy of Medical Sciences (IAMS) on November 25, 2019, at the Royal College of Surgeons in Ireland.AimsThe objective of this review was to obtain feedback and to examine the impact of GDPR and the HRRs on health research in Ireland in order to determine whether the preliminary feedback, presented at the IAMS meetings, was reflected at a national level.MethodsIndividuals from the research community were invited to provide feedback on the impact, if any, of the HRRs on health research. Retrospective patient recruitment and consent outside a hospital setting for a multi-institutional Breast Predict study (funded by the Irish Cancer Society) were also analysed.ResultsFeedback replicated the issues presented at the IAMS with additional concerns identified. Only 20% of the original target population (n = 1987) could be included in the Breast Predict study.ConclusionsOur results confirm that the HRRs have had a significantly negative impact on health research in Ireland. Urgent meaningful engagement between patient advocate groups, the research community and legislators would help ameliorate these impacts.

MP53-07 DOES ABDOMINAL AND PELVIC ADIPOSE TISSUE DISTRIBUTION IMPACT PROSTATE CANCER-SPECIFIC OUTCOMES AFTER RADIATION THERAPY?

You have accessJournal of UrologyProstate Cancer: Localized: Radiation Therapy (MP53)1 Apr 2020MP53-07 DOES ABDOMINAL AND PELVIC ADIPOSE TISSUE DISTRIBUTION IMPACT PROSTATE CANCER-SPECIFIC OUTCOMES AFTER RADIATION THERAPY? Claire M. Di Bella*, Lauren E. Howard, Taofik Oyekunle, Amanda M. De Hoedt, Joseph K. Salama, Stephen J. Freedland, and Emma H. Allott Claire M. Di Bella*Claire M. Di Bella* More articles by this author , Lauren E. HowardLauren E. Howard More articles by this author , Taofik OyekunleTaofik Oyekunle More articles by this author , Amanda M. De HoedtAmanda M. De Hoedt More articles by this author , Joseph K. SalamaJoseph K. Salama More articles by this author , Stephen J. FreedlandStephen J. Freedland More articles by this author , and Emma H. AllottEmma H. Allott More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000915.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Many studies examining the obesity-prostate cancer link rely on body mass index (BMI), a measure of overall obesity. Obesity is a heterogeneous phenotype, and fat distribution varies even between individuals of similar BMI. We hypothesized that excess visceral adipose tissue, the most metabolically active fat type, would be more strongly associated with poor prostate cancer outcomes than overall obesity. METHODS: We quantified visceral adipose tissue (both abdominal and pelvic) using CT scans from prostate cancer patients treated with radiation at the Durham NC Veterans Administration. Abdominal visceral fat area (VFA) was measured at L4/L5 and periprostatic adipose tissue (PPAT) area at the pubic symphysis by thresholding on Hounsfield Units -190 to -30, with both measures categorized as ≥ vs. < median. Pre-radiotherapy height and weight was abstracted from medical records and used to calculate BMI, categorized as ≥30 vs. <30 kg/m2. Recurrence was defined according to the Phoenix definition. Cox proportional hazards analysis examined associations between overall, and visceral (abdominal and pelvic) obesity and risk of recurrence, adjusting for age, race, year, biopsy Gleason, biopsy PSA, clinical stage, and receipt of androgen deprivation therapy (ADT). We performed stratified analysis by ADT receipt. RESULTS: Of 401 prostate cancer patients treated with radiation from 2005-2011, 84 (21%) experienced recurrence during a 9 year median follow-up. Overall obesity defined as BMI ≥30 was not associated with risk of recurrence overall or stratified by ADT. Nor was any measure of visceral obesity related to risk of recurrence overall. However, associations between visceral obesity and risk of recurrence varied by ADT receipt. Higher VFA was suggestively associated with increased risk of recurrence in men who received radiation only (HR 1.79; 95%CI 0.87-3.66), but inversely associated with recurrence risk in men treated with radiation + ADT (HR 0.49; 95%CI 0.24-1.03; p-heterogeneity=0.002). Similarly, higher PPAT was weakly associated with increased risk of recurrence in men treated with radiation only (HR 1.33; 95%CI 0.71-2.48), but inversely associated with recurrence risk in men who received radiation + ADT (HR 0.46; 95%CI 0.23-0.93; p-heterogeneity=0.002). CONCLUSIONS: Associations between visceral obesity and recurrence risk differed significantly by ADT receipt. If confirmed, our findings suggest that visceral obesity may have varying effects on prostate cancer progression dependent on the hormonal environment of the individual. Source of Funding: NIH 1K24CA160653, Irish Cancer Society John Fitzpatrick Fellowship © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e784-e784 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Claire M. Di Bella* More articles by this author Lauren E. Howard More articles by this author Taofik Oyekunle More articles by this author Amanda M. De Hoedt More articles by this author Joseph K. Salama More articles by this author Stephen J. Freedland More articles by this author Emma H. Allott More articles by this author Expand All Advertisement PDF downloadLoading ...

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

SummaryBackgroundCarboplatin 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.MethodsIn 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).FindingsBetween 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.InterpretationWeekly 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.FundingCancer Research UK, Medical Research Council, Health Research Board in Ireland, Irish Cancer Society, Cancer Australia.

CN36 - Understanding chemotherapy: Group education sessions prior to commencing chemotherapy

BackgroundInformation about chemotherapy is complex. Access to information prior to treatment enables patients to gain a better understanding of their condition, lessen their concerns and enables them to make informed choices about treatment. Traditionally chemotherapy education was provided by oncology clinical nurse specialists (CNS) on an individual basis to patients before they started chemotherapy. Increasing numbers of patients and reduced staff resources lead to problems maintaining service. The Irish Cancer Society’s Daffodil Centres are committed to quality improvement across cancer services available to those affected by cancer. Mater Misericordiae University Hospital (MMUH) and the Irish Cancer Society’s Daffodil Centre collaborated on a group chemotherapy initiative in 2012 initiated in response to a high demand for education services. After a successful pilot the programme is now running in 8 hospitals across Ireland. In 2018 342 group education sessions were held with 1713 attendees. MethodsThe Cancer Nurse in the Daffodil Centre facilitates this programme using educational tools including a specially produced audiovisual support (DVD) and short oral and practical demonstrations to assist different learning styles. To conclude the CNS meets with the patients to discuss their individual plan. All attendees are asked to complete an evaluation form which is inputted into a database and the results collated. Results1217 completed the evaluation out of 1713 attendees. A number of themes emerged including: • Welcoming • Good information • Allayed concerns • Empowerment. Acknowledgement of the expertise of the nurse and other allied healthcare professionals who present at the session – medical social workers and dietitians. ConclusionsOverall satisfaction levels were very high in the programme including the information and content on the DVD and the information received and the way it was explained by the nurse. Of those who left comments they were very positive about the experience and for the opportunity to attend. By attending the session patients and their relative/friends were made to feel welcome. Their knowledge of chemotherapy and its side effects were greatly increased and their fears of commencing treatment were in many ways alleviated. Legal entity responsible for the studyThe author. FundingHas not received any funding. DisclosureThe author has declared no conflicts of interest.

CN59 - Measuring the impact of the Irish Cancer Society’s cancer information services

BackgroundThe Irish Cancer Society is committed to monitoring the impact of our Cancer Information Services (CIS) at 4key stages (prevention, support, survivorship and palliative) to demonstrate the positive changes our services bring to the people affected by cancer. CIS incorporates Cancer Nurseline (freephone cancer helpline) and Daffodil Centres (walkin cancer information and support centres) based in cancer centres. Both are staffed by specialist cancer nurses. CIS provides support, advice and information to anyone affected by cancer. The information provided is tailored to the needs of each individual enquirer giving them greater access to cancer support and information which complements the service provided by the clinical teams in hospitals or in the community. In 2018 there were 47371 contacts to the service. MethodsImpact Monitoring uses surveys (paper and online) to collect information from service users. The nurses recruited cancer support enquirers over a two month period during September and October 2018. An enquirers’ distress level was assessed (using distress screening) by the nurse to determine if they were suitable to take part in the survey. Consent was obtained from participants across all services. Returned surveys were entered into a database and analysed according to themes and patterns. All respondents were anonymous. ResultsCIS had many positive impacts. Enquirers to the service appreciated the opportunity to access information from a healthcare professional either by phone or within a Daffodil Centre. During analysis some of the main benefits of the service identified include • Increased knowledge of cancer and its symptoms • More supported and aware of emotional supports • More in control • Reduced anxiety. Accurate and reliable information from a CIS healthcare professional offered reassurance to patients. ConclusionsHaving access to a cancer nurse through the CIS gave cancer patients the opportunity to avail of support, information and advice as and when they needed it. Enquirers felt they could talk through their questions and concerns, with the nurse providing information and guidance which reassured them. Talking to a nurse helped people feel more supported, more knowledgeable about their cancer and hopeful about the future. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

Health Literacy Influences Men's Active and Passive Cancer Information Seeking

Background:For cancer prevention information to be effective, it must be accessible to its target populations. Prevalence of inadequate health literacy (HL) is high, but there is a dearth of information on the impact of HL on men's cancer information seeking.Objective:We investigated (1) men's cancer information seeking behaviors, (2) the effect of HL on men's cancer information seeking behavior, and (3) men's preferences for cancer information, considering their HL level. From a national perspective, we investigated men's information seeking behavior from the Irish Cancer Society (ICS), the largest provider of cancer information in Ireland.Methods:Men from adult literacy classes and men's groups were invited to complete a questionnaire. General and ICS-specific cancer information seeking behavior was investigated. Univariate and multivariate logistic regression models were conducted with “ever” seeking cancer information from any source, and actively seeking and passively acquiring ICS information as dependent variables.Key Results: Overall, 259 men completed the questionnaire and 44% had inadequate HL. About one-half of responders reported “ever” actively looking for cancer information. In the study group, 19% actively sought and 67% passively acquired ICS-specific information. In multivariate analysis, the odds of actively seeking (2.93; 95% CI [1.05, 8.15]) or passively acquiring (4.7; 95% CI [1.99, 11.05]) ICS-specific cancer information was significantly higher among those with adequate versus inadequate HL, respectively. HL was not significantly associated with odds of “ever” cancer information seeking in multivariate analysis (odds ratio 1.81; 95% CI [0.90, 3.63]). Men want information about cancer prevention. Suggested future cancer information sources differed by HL levels. General practitioners and the Internet were the preferred source for men with inadequate (53.3%) and adequate HL (57%), respectively.Conclusions:Men both passively acquire and actively seek cancer prevention information. Multimodal dissemination of cancer prevention information is necessary to reach a wide cross-section of men, including those with inadequate HL. This could potentially lower men's cancer burden and reduce gender inequalities in cancer mortality. [HLRP: Health Literacy Research and Practice. 2019;3(3):e147–e160.]Plain Language Summary: Most men get cancer prevention information by coming across it passively in their daily lives, instead of actively looking for this information. Men with low health literacy are less likely to obtain cancer information both passively and actively. Men want this information. Organizations need to make this information available in many places and formats (e.g., Internet, doctor, television, sports clubs).

An evaluation of the Irish Cancer Society’s 2018 lung cancer awareness campaign

An evaluation of the Irish Cancer Society’s 2018 lung cancer awareness campaign

After a Sharp Decline in HPV Vaccine Rates From 87% to 50%, Irish Health Experts, Politicians and NGOs Joined Forces To Turn The Tide, Helping to Increase Vaccination by 11%. This Is How We Did It

Background and context: Just three years ago, in 2015, HPV vaccination uptake in Ireland was running at 87%. The school-based program was going well, and thousands of girls had completed a two-dose vaccination course which will significantly reduce their risk of cervical cancer and other HPV-related diseases. This was achieved with limited public health messaging. Then an online campaign to undermine the vaccine began to gather momentum. A small number of stories surfaced on social media claiming links between the timing of the vaccination campaigns and the subsequent development of illnesses. The campaign against the vaccine went viral on social media, local radio - and, in November 2015, on a commercial television station - fear began to trump science. In the summer of 2016, when preliminary figures showed uptake had hit 50%, the Irish Cancer Society commenced a campaign to take decisive action. Aim: To reverse the decline in HPV vaccine and restore uptake to previous levels above 80%. Strategy/Tactics: For health campaigners, such as the Irish Cancer Society, the problem of falling HPV vaccine uptake was a perplexing one. The society had pushed hard for the introduction of the HPV vaccine which commenced in 2011. To address the problem the Irish Cancer Society developed an advocacy campaign which eventually led to the establishment of the HPV Vaccination Alliance, a large group of leading health, children and women's groups, with the aim of ensuring that the public saw a broad coalition standing up for the vaccine. The Alliance has simple and consistent messages - including the fact that 40 women will die each year as a result of parents opting out of the vaccination program. Work was done to ensure that politicians were strongly supportive of the vaccine including political briefings with politicians who had previously sought to question its effectiveness. Young women with cervical cancer endorsed the campaign. The Minister for Health strongly endorsed the vaccine. The credibility of support groups for those with reported side effects of the vaccine was undermined by highlighting their links with national and international antivaccine activists as well as highlighting their repeated refusal to answer questions about where they spent money raised from the general public. Outcomes: Figures show uptake of the vaccine has increased to 61% in 2017 - up from 50% in 2016. What was learned: Not enough was done to support the initial implementation of the vaccine which created an information vacuum and under informed vaccination teams. The answer was a classic example of good public health advocacy in action demonstrating the power of alliances delivering consistent, clear and simple messaging.

National Cancer Societies and their public statements on alcohol consumption and cancer risk.

Studies have shown that alcohol consumption is a risk factor for oral, pharyngeal, laryngeal, esophageal, liver, colon, rectal and breast cancer. It would therefore be expected that cancer prevention organizations would incorporate these facts into their public stance on the consumption of alcohol. The aims of this study were to: (1) assess how national cancer societies in developed English-speaking countries [i.e. English-speaking countries belonging to the Organization for Economic Co-operation and Development (OECD)] communicate alcohol-related cancer risk to the public and (2) compare whether these organization's advocacy of increased alcohol taxes is in line with their advocacy of tobacco tax increases to reduce cancer risk. We searched the websites of the following national cancer organizations for all statements related to the relationship between alcohol consumption and cancer risk: Cancer Council Australia, Canadian Cancer Society, Irish Cancer Society, Cancer Society New Zealand, Cancer Research UK and the American Cancer Society. A categorical system was developed to code the qualitative data for health statements, alcohol consumption recommendations, and tax policy recommendations. Websites were analyzed in March of 2017. All organizations, with the exception of the American Cancer Society and Canadian Cancer Society, state that alcohol is a group 1 carcinogen and that even low-level alcohol consumption increases risk for some cancers. Additionally, while the American Cancer Society supports increasing tobacco taxes through its cancer action network, it has not advocated for increased alcohol taxes in relation to support for tobacco tax increases. Analysis in 2017 of the websites for national cancer societies in Australia, Canada, Ireland, New Zealand, the United Kingdom and the United States-including Cancer Council Australia, the Canadian Cancer Society, the Irish Cancer Society, Cancer Society New Zealand, Cancer Research UK and the American Cancer Society-shows that only the American Cancer Society and Canadian Cancer Society websites fail to state that alcohol is a group 1 carcinogen and can cause cancer at low doses, and that there is no safe threshold for cancer risk.

Abstract P5-10-02: High expression of BAD, PUMA, BOK and TRADD mRNA is associated with higher overall survival in ER+ and PR+ breast cancer patients

Abstract Background: Apoptosis signalling is controlled by a complex interaction of pro- and anti-apoptotic BCL2 proteins and its dysregulation is believed to be a major contributor to therapy responses and resistance in cancer. We previously demonstrated that inhibition of cell death in cancer cell is associated to poor outcome in colorectal cancer (Lindner et al., Cancer Res, 2012) and to lower cell death in triple negative breast cancer (TNBC) cells in vitro (Lucantoni et al., in review). In ER+ breast cancer, the anti-apoptotic protein BCL2 is commonly overexpressed, but its expression is associated with improved clinical outcome. The aim of this study was to assess whether system modelling of BCL2 protein interactions stratifies low- and high-risk breast cancer patients, and to determine the contribution of apoptosis signalling in different molecular subtypes of breast cancer. Methods: Protein levels of BAK, BAX, BCL2 and BCL(X) were determined in fresh frozen, TNBC samples from the BREAST-PREDICT Irish Cancer Society Collaborative Research Centre cohort, using HeLa cells as standard in which absolute protein levels were previously determined. Clinical, protein level and gene expression datasets of 845 invasive breast carcinoma patients were accessed from The Cancer Genome Atlas project, and BCL2 protein profiles were calculated by linear regression based on the BREAST-PREDICT cohort. In both cohorts, profiles were used to calculate the stress dose required to induce mitochondrial apoptosis (η). Results: In contrast to experiments with TNBC cells in which a high η indicated lower rates of cell death in vitro (Lucantoni et al., in review), we found that in breast cancer patients, η ≤ 0 was associated with lower overall survival (OS) compare to η &amp;gt; 0 (HR 2.1, 95%CI 1.3-3.3, p &amp;lt; 0.01). η &amp;gt; 0 was associated with lower levels of cleaved caspase 7 compared to η ≤ 0 (ANOVA &amp; Tukey post-hoc; p &amp;lt; 0.1). Cleaved caspase 7 levels &amp;gt; mean were associated with improved OS compared to levels ≤ mean (HR 0.4, 95%CI 0.3-0.7, p = 0.001). High values of η were significantly associated with lower proliferation in ER/PR+ cancer (ANOVA &amp; Tukey post-hoc; p &amp;lt; 0.01), but not in HER2+ or TNBC. Next we performed hierarchical cluster analysis (ConsensusClusterPlus; Monti et al, Machine Learning, 2003) with 61 additional mRNAs and proteins which are not implemented in our systems modelling approach. We found a subgroup with high BAD, PUMA, BOK and TRADD mRNA expression levels in ER/PR+ breast cancer patients, independently of the value of η. ER/PR+, but not HER2+ or TNBC, patients with an averaged expression of these 4 mRNA &amp;gt; mean had significant higher OS compared with patients with an averaged expression ≤ mean (HR 0.4, 95%CI 0.2-0.9, p = 0.02). Conclusions: Impairment of apoptosis assessed solely on the levels of BAK, BAX, BCL2 and BCLX(L) proteins were not sufficient as prognostic marker in breast cancer patients. However, our analysis suggest that patients with ER/PR+ cancer cells potentially 'primed' towards apoptosis - via the expression of pro-apoptotic BAD, PUMA, BOK and TRADD - had a more favourable clinical outcome compared to patients with cancer cells lacking this priming. Citation Format: Lindner AU, Lucantoni F, Vareslija D, Resler A, Gallagher WM, Hill A, Young L, Prehn JHM. High expression of BAD, PUMA, BOK and TRADD mRNA is associated with higher overall survival in ER+ and PR+ breast cancer patients [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-10-02.

Abstract P1-09-02: Bromodomain inhibitors for the treatment of invasive lobular carcinoma

Abstract Invasive lobular carcinoma (ILC) is the second most common type of breast cancer after invasive ductal carcinoma (IDC), accounting for approximately 10-15% of all breast tumors. ILC is characterized by inactivation of E-Cadherin and neoplastic cells that invade the stroma in a "single-file" pattern. Women with ILC are usually older, have used hormone replacement therapy and are more likely to have hormone receptor–positive disease. ILCs have similar survival to IDCs at both five and 10 years, but despite this, the clinical course is distinct: ILCs are three times more likely to metastasize to the peritoneum, gastrointestinal tract, and ovaries and are more frequently bilateral. Therefore, tailored therapeutic options for this distinct, hard-to-treat subtype of breast cancer are required. As part of the RATHER FP7 HEALTH consortium (www.ratherproject.com), we carried out RNA-Seq analysis of 61 primary ILC samples and identified that high expression of the BET family protein Brd3 (uniquely among BRD family members) was associated with poor recurrence free survival (p=0.03, HR 8.63, CI 1.22-60.85). This observation was further validated in the independent METABRIC cohort (n=99), where again, high Brd3 expression (and not other BRD members) was associated with poor recurrence-free survival (p&amp;lt;0.01, HR=3.16, CI 1.24-8.03). Using a two ILC cell lines (SUM44PE and MDA-MB134VI) we found that ILC cells were relatively resistant to the anti-estrogen therapies tamoxifen and fulvestrant compared to those derived from IDC. Next, we tested whether the ILC cell lines were sensitive to BET protein inhibition using the pan-BET family inhibitor JQ1. Interestingly, while JQ1 inhibited cell growth in both ILC cell lines tested, apoptosis was only induced in SUM44PE cells, while MDA-MB134VI cells exhibited G1 arrest. Dynamic BH3 profiling was used to dissect the underlying anti-apoptotic dependencies in each ILC cell type and showed that in the JQ1-resistant MDA-MB134VI cells, survival was predominantly Bcl2-dependent. Combination of JQ1 and the Bcl2-inhibitor venetoclax (ABT-199) synergistically killed MDA-MB134V1 cells compared to treatment with JQ1 alone, while combination with the Bcl2/Bcl-Xl/Bcl-W inhibitor navitoclax (ABT-263) added further synergy. With a number of BET inhibitors now entering clinical trials, the data described here suggest that BET inhibition is a rational therapeutic option for some ILC cases, and for those that do not respond, combination with venetoclax may be a suitable therapeutic strategy. In our cell line models, baseline Bcl-2 expression was sufficient to predict induction of apoptosis in response to JQ1 and could be used to guide therapeutic choice. These results should now be investigated in vivo before a prospective clinical trial. This material is based upon works supported by the Irish Cancer Society Collaborative Cancer Research Centre BREAST-PREDICT Grant CCRC13GAL" and the SFi CDA Award 15/CDA/3438 Citation Format: O'Connor DP, Walsh L, Fan Y, Tarrant F, Chin S-F, Schouten P, Caldas C, Bernards R, Ni Chonghaile T, Gallagher WM. Bromodomain inhibitors for the treatment of invasive lobular carcinoma [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-09-02.

Effects of sampling frequency on the accuracy of phenomenological and pharmacokinetic parameters derived from dynamic contrast enhanced MRI data

The sampling frequencies (fs) at which dynamic contrast enhanced (DCE) MRI data are acquired is known to affects the accuracy of derived parameters. Phenomenological parameters empirically characterise the shape and structure of the signal-time curves, whereas pharmacokinetic approaches estimate physiologically relevant parameters from the concentration-time curves, such as the volume-transfer constant (Ktrans) and the extravascular-extracellular fractional volume (ve). Both of these approaches have shown promise in the detection of prostate cancer, however to date a method has been lacking to quantitatively compare MR-measured to known ‘ground truth’ parameter values. In the present work, a newly developed anthropomorphic DCE-MRI prostate phantom was utilised to this end. Precisely known ‘healthy’ and ‘tumorous’ curves were measured using a 3T scanner (Philips, Netherlands) and 32-channel detector coil (3D-SPGR, TR/TE = 4.3/1.4 ms, α  = 10°, FOV = 224 × 224 × 80 mm3, voxels = 1 × 1 × 4 mm3) at fs = 0.5, 0.26, 0.19, 0.12, 0.061, and 0.041 Hz. Phenomenological analysis revealed that wash-in was measured with the lowest errors ( 15%) at fs  ⩾  0.12 Hz, whereas wash-out gave comparatively higher errors (up to 27%) across this same range of fs. Lowest errors in time-to-peak ( 11%) were measured using fs = 2 s and 8.1 s. Pharmacokinetic analysis using the Tofts model gave errors in Ktrans and ve values 14% and 10%, for acquisitions with fs  ⩾  0.12 Hz and fs  ⩾  0.061 respectively, with errors increasing dramatically (up to 172%) with fs   0.061 Hz. Quantitative phantom-based approaches, such as the one used herein, offers the prospect of a standardisation in the way DCE-MRI is performed in the prostate, and possibly a wider acceptance of the technique for routine clinical use. Acknowledgement This work is funded by Irish Cancer Society Research Scholarship CRS13KNI (supported by Movember).

Abstract P6-11-06: Bromodomain inhibitors represent a rational therapeutic option for the treatment of invasive lobular carcinoma

Abstract Invasive lobular carcinoma (ILC) is the second most common type of breast cancer after invasive ductal carcinoma (IDC), accounting for approximately 10-15% of all breast tumors. ILC is characterized by inactivation of E-Cadherin and neoplastic cells that invade the stroma in a "single-file" pattern. Women with ILC are usually older, have used hormone replacement therapy and are more likely to have hormone receptor–positive disease. ILCs have similar survival to IDCs at both five and 10 years, but despite this, the clinical course is distinct: ILCs are three times more likely to metastasize to the peritoneum, gastrointestinal tract, and ovaries and are more frequently bilateral. Therefore, tailored therapeutic options for this distinct, hard-to-treat subtype of breast cancer are required. As part of the RATHER FP7 HEALTH consortium (www.ratherproject.com), we carried out RNA-Seq analysis of 61 primary ILC samples and identified that high expression of the BET family protein Brd3 was associated with poor recurrence free survival (p=0.03, HR 8.63, CI 1.22-60.85). This observation was further validated in the independent METABRIC cohort (n=99), where again, high Brd3 expression was associated with poor recurrence-free survival (p&amp;lt;0.01, HR=3.16, CI 1.24-8.03). Using a two ILC cell lines (SUM44PE and MDA-MB134VI) we found that ILC cells were relatively resistant to the anti-estrogen therapies tamoxifen and fulvestrant compared to those derived from IDC. Next, we tested whether the ILC cell lines were sensitive to BET protein inhibition using the pan-BET family inhibitor JQ1. Interestingly, while JQ1 inhibited cell growth in both ILC cell lines tested, apoptosis was only induced in SUM44PE cells, while MDA-MB134VI cells exhibited G1 arrest. Dynamic BH3 profiling was used to dissect the underlying anti-apoptotic dependencies in each ILC cell type and showed that in the JQ1-resistant MDA-MB134VI cells, survival was predominantly Bcl2-dependent. Combination of JQ1 and the Bcl2-inhibitor venetoclax (ABT-199) synergistically killed MDA-MB134V1 cells compared to treatment with JQ1 alone, while combination with the Bcl2/Bcl-Xl/Bcl-W inhibitor navitoclax (ABT-263) added further synergy . With a number of BET inhibitors now entering clinical trials, the data described here suggest that BET inhibition is a rational therapeutic option for some ILC cases, and for those that do not respond, combination with venetoclax may be a suitable therapeutic strategy. In our cell line models, baseline Bcl-2 expression was sufficient to predict induction of apoptosis in response to JQ1 and could be used to guide therapeutic choice. These results should now be investigated in vivo before a prospective clinical trial. "This material is based upon works supported by the Irish Cancer Society Collaborative Cancer Research Centre BREAST-PREDICT Grant CCRC13GAL". Citation Format: O'Connor DP, Walsh L, Tarrant F, Chin S-F, Schouten P, Linn S, Bernards R, Caldas C, Gallagher WM, ni Chonghaile T. Bromodomain inhibitors represent a rational therapeutic option for the treatment of invasive lobular carcinoma [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-11-06.

P2.08-014 Lung Cancer Awareness and Barriers to Primary Care in Ireland: Topic: Other

Lung cancer is the leading cause of cancer death in both men and women in Ireland. * Previous research has shown awareness of lung cancer is high yet the majority of lung cancer patients continue to be diagnosed at an advanced stage.** In 2015 the Irish Cancer Society performed an online survey to examine the attitudes of the public in relation to the signs and symptoms of lung cancer and identify the perceived barriers for people accessing their GPs/pharmacists with symptoms. Objectives:•Test awareness of prevalence, symptoms, causes and impact of lung cancer.•Examine the incidence of recent interactions with health care professionals on the subject of lung health.•Identify the barriers to accessing primary care for lung cancer symptoms.•Examine the experiences of those who have had interactions. Online survey of 1000 adults and booster sample of 100 smokers 65+. Sample was quota controlled on gender, age, social class and region to ensure a representative sample. •47% identified lung cancer as the leading cause of cancer death in Ireland.•Half of Irish adults and 31% of smokers claim to be unconcerned about being diagnosed with the disease.•79% of smokers claimed to have never spoken with a doctor/pharmacist about lung health and 59% of smokers have never spoken with a doctor/pharmacist about giving up smoking.•54% said they would not go to their doctor if they had one or more symptoms of lung cancer due to obstacles like fear (22%), expense of doctor’s visit (17%), because it is not serious enough (19%).•37% of smokers would be discouraged from visiting a doctor with symptoms.•Reasons included don’t think there is much a doctor can do for their lung health (11%), worried about what they would be told (32%), too expensive (20%) and don’t want a lecture on smoking (20%). This study reveals a number of barriers to early detection of lung cancer which in turn can lead to late diagnoses. These include a lack of awareness and underestimating the severity of the disease. The cost, anxiety, and fatalistic attitude are barriers which can influence the design of a lung cancer awareness campaign. Enabling health professionals and establishing accessible services to address lung health with high risk populations in a supportive manner will improve early detection of lung cancer.