Cancer Alliance Research Articles

Multi-Institutional Prospective Validation of Prognostic mRNA Signatures in Early Stage Squamous Lung Cancer (Alliance).

Surgical resection is curative for some patients with early lung squamous cell carcinoma. Staging and clinical factors do not adequately predict recurrence risk. We sought to validate the discriminative performance of proposed prognostic gene expression signatures at a level of rigor sufficient to support clinical use. The two-stage validation used independent core laboratories, objective quality control standards, locked test parameters, and large multi-institutional specimen and data sets. The first stage validation confirmed a signature's ability to stratify patient survival. The second-stage validation determined which signature(s) optimally improved risk discrimination when added to baseline clinical predictors. Participants were prospectively enrolled in institutional (cohort I) or cooperative group (cohort II) biospecimen and data collection protocols. All cases underwent a central review of clinical, pathologic, and biospecimen parameters using objective criteria to determine final inclusion (cohort I: n= 249; cohort II: n= 234). Primary selection required that a signature significantly predict a 3-year survival after surgical resection in cohort I. Signatures meeting this criterion were further tested in cohort II, comparing risk prediction using baseline risk factors alone versus in combination with the signature. Male sex, advanced age, and higher stage were associated with shorter survival in cohort I and established a baseline clinical model. Of the three signatures validated in cohort I, one signature was validated in cohort II and statistically significantly enhanced the prognosis relative to the baseline model (C-index difference 0.122; p < 0.05). These results represent the first rigorous validation of a test appropriate to direct adjuvant treatment or clinical trials for patients with lung squamous cell carcinoma.

Service evaluation of faecal immunochemical testing introduced for use in North East London for patients at low risk of colorectal cancer

AimsColorectal cancer (CRC) is the fourth most common cancer in the UK. Following National Institute of Clinical Excellence (NICE) guidance for faecal immunochemical testing (FIT) (DG30), we introduced a service...

A Single-centre Audit of Time from Surgery to Adjuvant Radiotherapy in Breast Cancer Patients Treated at the Royal Free Hospital

Purpose: Adjuvant radiotherapy is a key component in breast cancer management. Following multidisciplinary discussion and wound healing, patients are counselled for postoperative radiotherapy by a clinical oncologist, then proceed to radiotherapy planning. The London Cancer Alliance 2016 guidance stipulates breast irradiation should be commenced as soon as possible following surgery, but no later than 12 weeks [1]. This audit aimed to determine our centre’s compliance with this guidance and identify any reversible factors causing delay.

Abstract B07: Ovarian cancer stem-like cells and alternately activated macrophages reciprocally interact through the WNT pathway to promote protumoral and malignant phenotypes in 3D engineered microenvironments

Abstract Background: Innate immune cells such as macrophages are abundantly present within malignant ascites, where they share the microenvironment with ovarian cancer stem cells (CSC). Methods: To mimic this malignant ascites microenvironment, we created a hanging-drop hetero-spheroid model to bring CSCs and macrophages in close association. Within these hetero-spheroids, CD68+ macrophages (derived from U937 or peripheral blood monocytes) make up ~20% of the population, while the rest are ovarian cancer cells and ovarian cancer stem cells (derived from the high-grade serous ovarian cancer cell line, OVCAR3). Results: Our results indicate that CSCs drive the upregulation of M2 macrophage marker CD206 within hetero-spheroids, compared to bulk ovarian cancer cells, implying an inherently more immunosuppressive program. Moreover, an increased maintenance of elevated aldehyde dehydrogenase (ALDH) activity is noted within hetero-spheroids that include prepolarized CD206+ M2 macrophages, implying a reciprocal interaction that drives protumoral activation as well as CSC self-renewal. Consistent with enriched CSCs, we also observe increased levels of protumoral IL-10 and IL-6 cytokines in the CSC/M2-macrophage hetero-spheroids. CSC/M2-macrophage hetero-spheroids are also less sensitive to the chemotherapeutic agent carboplatin and are subsequently more invasive in transwell assays. Using inhibitors of WNT secretion in both CSCs and macrophages, we found that CSC-derived WNT ligands drove CD206+ M2 macrophage activation, and that, conversely, macrophage-derived WNT ligands enriched ALDH+ cells within the CSC compartment of hetero-spheroids. Upon examination of specific WNT ligand expression within the monocyte-derived macrophage system, we observed a significant elevation in gene expression for WNT5B. In CSCs co-cultured with macrophages within hetero-spheroids, increases in several WNT ligands were observed, and this increase was significantly inhibited when WNT5B was knocked down in macrophages. Conclusions: Our data imply that macrophage-initiated WNT signaling could play a significant role in the maintenance of stemness, and the resulting phenotypes of chemoresistance and invasiveness. Our results indicate paracrine WNT activation during CSC/M2 macrophages interaction constitutes a positive feedback loop that likely contributes to the more aggressive phenotype, which makes the WNT pathway a potential target to reduce the CSC and M2 macrophage compartments in the tumor microenvironment. Acknowledgments: This work was supported by the DOD OCRP W81XWH-13-1-0134 (GM), Michigan Ovarian Cancer Alliance (MIOCA, GM), Rivkin Center for Ovarian Cancer (GM), NIH/NIDCR DE026728 (YLL) and the NIH/NIDCR T32DE00007057-41, 42 (SR). Flow cytometry facilities used to perform experiments were partially funded by NIH/NCI P30CA046592. Citation Format: Shreya Raghavan, Pooja Mehta, Yuying Xie, Yu L Lei, Geeta Mehta. Ovarian cancer stem-like cells and alternately activated macrophages reciprocally interact through the WNT pathway to promote protumoral and malignant phenotypes in 3D engineered microenvironments [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr B07.

Implementing Community-Based Prostate Cancer Education in Rural South Carolina: a Collaborative Approach Through a Statewide Cancer Alliance.

The purpose of this study was to evaluate the impact of implementing community-based prostate health education programs in rural communities. Prostate cancer (PrCA) remains one of the most common cancers among men, and a growing body of literature demonstrates that large interracial differences in PrCA incidence and mortality rates consistently disfavor African Americans in comparison to European Americans. It also is evident, despite the overall decrease in cancer death rates in the USA in recent decades, rural areas are experiencing a reduction in death rates much more slowly. In this study, education session content focused on PrCA risk factors, symptoms, screening, healthy diet and exercise, treatment options, and provider communication strategies. Forty individuals participated and completed pre/post-education program surveys to assess changes in PrCA knowledge and cancer decision-making. Participants showed improvements in education and awareness following the session, and overall impressions of the program were consistently positive as exhibited by participants' answers on a satisfaction survey. The findings demonstrate the real need both in terms of research to understand the underlying problem and to provide practical solutions that can be implemented to reverse the current situation. The results obtained support community-based education programs as an effective means of delivering PrCA prevention, screening, and treatment information to rural communities.

A population-based study of young-onset colorectal cancer patients: Effect of knowledge gaps among patients and providers on stage at diagnosis and quality of life.

4095 Background: Colorectal cancer (CRC) is one of the leading cause of cancer-related death in the US. Despite a decrease in overall incidence and mortality, there has been an alarming increase in CRC diagnosis among young adults (20-49 years old) and causes remain unknown. To explore the unique challenges and unmet needs of the young-adult patients many still establishing their life-long goals, the Colorectal Cancer Alliance launched a comprehensive survey for young-onset CRC patients and survivors via social media to track the self-reported pre-diagnosis awareness, path to diagnosis, and post-diagnosis quality of life experiences of this often overlooked group. Methods: A cross-sectional study, conducted in the form of an online survey, was launched via multiple channels of social media. The questionnaire was based on established instruments including PROMIS, EORTC-QOL-30, and EORTC-CR-29 and EORTC-SHC-22. Results: The survey was completed by 885 patients and survivors. The median age at diagnosis was 42 +/-7, significantly lower than the recommended screening age. Only 6% of respondents were diagnosed with Lynch syndrome although 29% reported some family history. Most respondents (63%) indicated they were not aware that CRC can affect people younger than 50, which may explain why the majority of patients waited more than 3 months and 23% waited over 12 months after noticing their symptoms to visit their doctor. The majority, 75%, of all patients visited 2+ doctors and 11% of those patients visited 10+ doctors before their doctor suspected colorectal cancer. A significant number of patients felt their doctors were dismissive of their symptoms. 77% of patients were diagnosed with advanced disease and were subjected to aggressive therapies that substantially affected their quality of life including neuropathy, anxiety, clinical depression, sexual morbidity, unemployment, and financial toxicity. Many young patients indicated that their doctors did not inform them about fertility preservation. Conclusions: Our survey indicates that medical professionals and young adults need to be aware of the increasing incidence of young-onset CRC, and the importance of timely screening when signs and symptoms are present, regardless of age.

Gaps in Knowledge and Understanding of Patients With Metastatic Breast Cancer in Mexico.

There is paucity of data regarding the knowledge and understanding of patients with metastatic breast cancer (MBC) about their disease stage and treatment goals. This study assessed these patients’ awareness of MBC incurability, topics reviewed with their oncologist, perceptions of having enough knowledge to participate in treatment decision-making, most helpful information source, and satisfaction with the information they received. For this purpose, 185 patients with MBC who attended follow-up medical appointments at a Mexican referral cancer center completed a survey designed by the Metastatic Breast Cancer Alliance. Clinical data were obtained from medical records. Descriptive statistics were applied, and associations between qualitative and quantitative variables were assessed with χ2 and Mann-Whitney U tests, respectively. Half (52%) of the patients were aware that their disease was incurable, while 31% were not sure, and 17% thought it was curable. Forty percent found it difficult to talk about treatments because they did not understand the options that were available to them. The medical staff was the most helpful information source for 74% of participants, and 64% scored their satisfaction with information ≥9 of 10. A significant association was found between higher satisfaction and knowing that MBC is incurable, as well as being older than 40 years. These results illustrate the significant lack of understanding patients with MBC have regarding their cancer, even when reporting high satisfaction with the provided information, and identify a critical need for improved patient education to enhance their comprehension and promote their participation in decision-making processes, treatment adherence, and, ultimately, outcomes.

Outcomes of the National Head and Neck Cancer Awareness and Screening Campaign in Oman.

ObjectivesThe prognosis of head and neck cancer (HNC) depends substantially on disease stage at the time of diagnosis. Unfortunately, the majority of HNC patients present at relatively late stages. In Oman, a national screening campaign was conducted to increase public awareness of HNC and encourage early detection. This study aimed to report the outcomes of that campaign.MethodsThe campaign took the form of biannual events conducted at a tertiary care centre and in public malls in Muscat, Oman from April 2015 to July 2019. Data were collected from participants using the Head and Neck Cancer Alliance screening form. Otolaryngologists and oral maxillofacial surgeons performed a thorough physical evaluation of the head and neck region.ResultsOf the 1,500 individuals visiting the hospital and malls during the campaign events, a total of 509 agreed to undergo screening (response rate: 33.9%). Of these, 12.8% had positive screening results and 5.9% required further evaluation. However, none of the cases with suspicious findings were found to be malignant after a thorough evaluation. Overall, 16.9% of the participants were aware of the early signs of HNC; in addition, 5.5% knew how to perform an oral self-examination.ConclusionScreening is a simple and safe method for the prevention and early detection of HNC. Mass screening and public awareness programmes may help to reduce the burden of this disease in Oman.

Abstract P1-16-02: Survey of Lobular Breast Cancer Alliance website users confirms value and identifies unmet information needs

Abstract Introduction The Lobular Breast Cancer Alliance (LBCA) was founded in 2017 by patient advocates attending the First International Invasive Lobular Breast Cancer Symposium sponsored by the University of Pittsburgh. The conference underscored that invasive lobular breast cancer (ILC) is an understudied unique subtype of breast cancer requiring refinements in treatments. ILC is the sixth most frequently diagnosed cancer of women and the second most common histological subtype of breast cancer with more than 39,000 patients diagnosed a year in the U.S. LBCA’s goals are to advance research and educate about ILC. Challenges An early goal of LBCA was to address the absence of a central source of quality information about lobular breast cancer. A website, lobularbreastcancer.org, launched December, 2017 with over 98,000 hits to-date. It is maintained by patient-advocate volunteers with content reviewed by LBCA’s Scientific Advisory Board. Methods A survey of users was conducted from May 1 to June 3, 2019 to determine value of the website to users and identify potential ways to improve it. Specific goals were: Understand who was visiting the site, identify the information sought, obtain feedback on the usefulness of content, and seek input on content and navigation. Results The online survey was taken by 950 participants. Current or former patients treated for lobular breast cancer comprised 94.7% of respondents. 75.8% were from U.S. Health professionals/researchers represented 3.04% of responders. Patients ranged in age from under 35 to over 75 years; 71.5% were 46-65 years. Most (66.5%) had Stage 1-2 disease at time of diagnosis; 7% reported de novo metastatic disease. An additional 9% reported a metastatic recurrence. LBCA (43.8%), other cancer organizations (43.2%),and Internet searches (38.3%) were the most frequently used sources for information about lobular breast cancer; doctor/health care provider ranked fourth (35.3%). The survey confirmed that LBCA goals for the website were aligned with the reason responders visited - i.e., general information (33%), research/clinical trials (21.9%) and treatment information (17.8%). Most consulted the site 2-4 times (46%), 11% visited more than 10 times. Nearly all responders (83.7%) found the information they were seeking, and (45.4%) agreed that the LBCA website provided information they could not find elsewhere. There were 249 participants who responded to an open ended question with 273 recommendations for the site. The largest category of requests (17%) was for more frequent updates of research and treatment guidelines; requests for a list of providers with expertise in treating ILC patients and for LBCA to provide additional education about ILC to MDs/clinicians ranked second and third (11%). Conclusions LBCA is driving increased awareness of lobular breast cancer by sponsoring a website devoted to providing research-based information about lobular breast cancer. There were a number of actionable suggestions regarding organization and navigation of the LBCA website. Results confirmed that the LBCA goals for the website are aligned with the reason responders visited. Primarily, users searched for general information about ILC (33%), research/clinical trials (21.9%) and treatment information (17.8%). The need for a central online source for information about lobular breast cancer was confirmed by findings that the most frequently used sources of information about lobular were the LBCA, other cancer organizations and Internet searches. Doctors/health care providers ranked fourth as a source of information about lobular disease. Many responders wanted the website to list ILC treatment specialists, address the gap in provider expertise about ILC detection and treatment, and report research and treatment guidelines specifically for ILC. Citation Format: Lori Petitti, Janice Axelrod, Margaret Campbell-Kotler, Julia Levine, Flora Migyanka, Elizabeth Viggiano, Steffi Oesterreich, Leigh Pate. Survey of Lobular Breast Cancer Alliance website users confirms value and identifies unmet information needs [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-16-02.

Patient familiarity with, understanding of, and preferences for clinical trial endpoints and terminology.

Although there is increased attention to designing and explaining clinical trials in ways that are clinically meaningful for patients, there is limited information on patient preferences, understanding, and perceptions of this content. Maximum difference scaling (MaxDiff) methodology was used to develop a survey for assessing patients' understanding of 19 clinical terms and perceived importance of 9 endpoint surrogate phrases used in clinical trials and consent forms. The survey was administered electronically to individuals with metastatic breast cancer affiliated with the Metastatic Breast Cancer Alliance. Analyses were performed using Bayesian P values with statistical software. Among 503 respondents, 77% had a college degree, 70% were diagnosed with metastatic disease ≥2years before survey completion, and 77% had received ≥2 lines of systemic therapy. Less than 35% of respondents reported understanding "fairly well" the terms symptomatic progression, duration of disease control, time to treatment cessation, and endpoints. Income level and time since onset of metastatic disease correlated with comprehension. Patients who had received ≥6 lines of therapy perceived that time until serious side effects (P<.001) and time on therapy (P<.001) were more important compared with those who had received only 1 line of therapy. Positively phrased parameters were associated with increased perceived importance. Even among educated, heavily pretreated patients, many commonly used clinical research terms are poorly understood. Comprehension and the perceived importance of trial endpoints vary over the course of disease. These observations may inform the design, discussion, and reporting of clinical trials.

71 - Exploring variability in %predicted DLCO during pre-operative assessment for lung cancer resection across a cancer alliance

71 - Exploring variability in %predicted DLCO during pre-operative assessment for lung cancer resection across a cancer alliance

The case for philanthropic investment to increase colorectal cancer screening rates: A novel paradigm to address a public health challenge.

BackgroundColorectal cancer (CRC) remains a leading cause of cancer‐related death despite being highly preventable. Efforts to increase participation in CRC screening have not met national goals. We developed a novel approach: building a business case for philanthropic investment in CRC screening.MethodsA taskforce representing the public health community, professional societies, charitable foundations, academia, and industry was assembled to: (a) quantify the impact of improving CRC screening rates; (b) identify barriers to screening; (c) estimate the “activation cost” to overcome barriers and screen one additional person; (d) develop a holistic business case that is attractive to philanthropists; and (e) launch a demonstration project.ResultsWe estimated that of 50 600 CRC deaths annually in the US, 55% occur in 50‐ to 85‐year‐olds and are potentially addressable by improvements in CRC screening. Barriers to screening were identified in all patient journey phases, including lack of awareness or insurance and logistical challenges in the pre‐physician phase. The cost to activate one person to undergo screening was $25‐175. This translated into a cost of $6000‐36 000 per CRC death averted by philanthropic investment. Based on this work, the Colorectal Cancer Alliance launched the effort “March Forth” to prevent 100 000 CRC deaths in the US over 10 years, with the first pilot in Philadelphia.ConclusionsA holistic business plan can attract philanthropy to promote CRC screening. A simple message of “You can save a life from CRC with a $25 000 donation” can motivate demonstration projects in regions with high CRC rates and low screening participation.

Using linked English cancer registration data to assess variation in diagnostic pathway length

BackgroundFor the majority of cancer patients, the length of the diagnostic pathway is unknown. Only those on a specific pathway are monitored. Quantifying pathway length is important in understating which patients may benefit most from an expedited pathway.&#x0D; AimThis study aimed to develop a novel methodology using linked cancer registration data to calculate the Secondary Care Diagnostic Interval (SDCI): the period from first interaction with secondary care to receiving a cancer diagnosis. Subsequently variation in SCDIs across twenty-five cancer sites were analysed.&#x0D; MethodsEnglish cancer registrations (2014-15) from Public Health England’s National Cancer Registration and Analysis Service were linked to three routine health datasets: Hospital Episode Statistics, Diagnostic Imaging Dataset and Cancer Waiting Times.&#x0D; The SCDI was calculated as the difference between the earliest event relating to the secondary care diagnostic process (comprised of referral into/secondary care appointment or diagnostic procedure in the 6 months before diagnosis) and the diagnosis date.&#x0D; SCDI length was stratified by stage at diagnosis, route to diagnosis (e.g. emergency presentation, GP referral) and patient characteristics.&#x0D; ResultsThe median SCDI (days) was shortest for acute lymphoblastic leukaemia (ALL) (2) and longest for kidney (45). In general, SCDIs decreased with later stage (for example stage 1-4 colorectal: 35 to 20, lung: 75 to 25). Patients diagnosed after routine GP referrals had longest SCDIs compared to urgent referrals, for all sites except ALL. Geographical variation in SCDIs exists by Cancer Alliance, with the greatest differences compared to the England average observed for prostate cancer (median national SCDI: 28, Cancer Alliance range: 21 - 42).&#x0D; ConclusionSubstantial variation exists in SCDIs by cancer site, stage and presentation route. Many patients are experiencing SCDIs over 28 days, even those diagnosed via urgent GP referrals. Understanding variation can support creation of targeted initiatives to expedite diagnostic pathways where appropriate.

Meeting Proceedings of the “Phase I: Where Science Becomes Medicine” Conference, Manchester, UK

Meeting Proceedings of the “Phase I: Where Science Becomes Medicine” Conference, Manchester, UK

Immune Checkpoint Profiles in Luminal B Breast Cancer (Alliance).

Unlike estrogen receptor (ER)-negative breast cancer, ER-positive breast cancer outcome is less influenced by lymphocyte content, indicating the presence of immune tolerance mechanisms that may be specific to this disease subset. A supervised analysis of microarray data from the ACOSOG Z1031 (Alliance) neoadjuvant aromatase inhibitor (AI) trial identified upregulated genes in Luminal (Lum) B breast cancers that correlated with AI-resistant tumor proliferation (percentage of Ki67-positive cancer nuclei, Pearson r > 0.4) (33 cases Ki67 > 10% on AI) vs LumB breast cancers that were more AI sensitive (33 cases Ki67 < 10% on AI). Overrepresentation analysis was performed using WebGestalt. All statistical tests were two-sided. Thirty candidate genes positively correlated (r ≥ 0.4) with AI-resistant proliferation in LumB and were upregulated greater than twofold. Gene ontologies identified that the targetable immune checkpoint (IC) components IDO1, LAG3, and PD1 were overrepresented resistance candidates (P ≤ .001). High IDO1 mRNA was associated with poor prognosis in LumB disease (Molecular Taxonomy of Breast Cancer International Consortium, hazard ratio = 1.43, 95% confidence interval = 1.04 to 1.98, P = .03). IDO1 also statistically significantly correlated with STAT1 at protein level in LumB disease (Pearson r = 0.74). As a composite immune tolerance signature, expression of IFN-γ/STAT1 pathway components was associated with higher baseline Ki67, lower estrogen, and progesterone receptor mRNA levels and worse disease-specific survival (P = .002). In a tissue microarray analysis, IDO1 was observed in stromal cells and tumor-associated macrophages, with a higher incidence in LumB cases. Furthermore, IDO1 expression was associated with a macrophage mRNA signature (M1 by CIBERSORT Pearson r = 0.62 ) and by tissue microarray analysis. Targetable IC components are upregulated in the majority of endocrine therapy-resistant LumB cases. Our findings provide rationale for IC inhibition in poor-outcome ER-positive breast cancer.

Co-Creation of a Lanreotide Autogel/Depot Syringe for the Treatment of Acromegaly and Neuroendocrine Tumours Through Collaborative Human Factor Studies

IntroductionAlthough the previous lanreotide autogel/depot syringe had been well received, feedback indicated that improvements could be made to make it more user-friendly. Additionally, the view that patients should have greater involvement in the research and development process is echoed by the International Neuroendocrine Cancer Alliance. A series of studies aimed to develop and validate a new syringe that works better for patients, caregivers and healthcare professionals (HCPs) by involving these groups at key stages in the development and testing process.MethodsThe multicentre, international, human factor studies, consisted of four formative studies and one validation study. The formative studies collected patient, caregiver and HCP feedback on the lanreotide autogel/depot syringe on the market at the time, and on newly designed prototypes. The validation study was conducted to evaluate the final syringe to confirm that it can be used effectively and safely in the intended environment, by the intended user, for the intended purpose.ResultsOverall, 213 individuals participated in the studies; 145 contributed to the formative studies and 68 to the validation study. The validated new-generation syringe included several important updates compared with the lanreotide autogel/depot syringe currently on the market, including the flanges, which are now larger and have a better grip; the overcap, which is white, ridged, opaque and bigger; the plunger supports and the thermoformed tray. No participant hurt themselves or others during the validation study (although several misuses were reported), and all participants succeeded in delivering a complete dose and activating the safety system.ConclusionWith collaboration, a new syringe was developed to meet the needs of patients, caregivers and HCPs, whilst ensuring lanreotide was delivered effectively and safely. These studies highlight the importance of involving patients, caregivers and HCPs in clinical evaluation studies to develop medical products that address their concerns and meet their needs.FundingIpsen.Plain Language SummaryPlain language summary available for this article.Electronic Supplementary MaterialThe online version of this article (10.1007/s12325-019-01112-3) contains supplementary material, which is available to authorized users.

Geographic variation in the use of lymphadenectomy and external-beam radiotherapy for endometrial cancer: a cross-sectional analysis of population-based data.

To quantify geographic variation in the use of lymphadenectomy and/or external-beam radiotherapy (EBRT) for endometrial cancer in England. Cross-sectional analysis of population-based data. English cancer registry data, linked to chemotherapy, radiotherapy and hospital episodes statistics data. Twenty-two thousand four hundred and eighty-three women with endometrial cancer presenting without clinical or radiological evidence of distant metastatic spread, diagnosed in England from 2013 to 2016. Proportions of patients receiving lymphadenectomy and/or EBRT were compared across 19 Cancer Alliances, to identify variations in clinical practice. Two separate logistic regression models assessed the impact on variation of adjustment for tumour and patient characteristics. Receipt of lymphadenectomy, receipt of EBRT. There was substantial variation by Cancer Alliance in the adjusted proportion of women with endometrial cancer receiving lymphadenectomy (range 5% [95% CI 4-6%] to 48% [95% CI 45-52%]) and EBRT (range 10% [95% CI 7-12%] to 31% [95% CI 28-33%]), after adjusting for variation in pathological grade, age, comorbidities, deprivation, ethnic group and (EBRT only) FIGO stage. Different approaches to clinical practice were identified; (i) one Cancer Alliance had significantly higher than average lymphadenectomy and significantly lower than average EBRT use, (ii) three had high use of both lymphadenectomy and EBRT, (iii) one had low lymphadenectomy use and high EBRT use, and (iv) three had low use of both lymphadenectomy and EBRT. Lymphadenectomy is probably used to triage for EBRT when lymphadenectomy use is high and EBRT use is low. This is probably a result of variation in local endometrial cancer management guidelines, suggesting that UK recommendations should be clarified. There is geographic variation in England in the use of lymphadenectomy and radiotherapy to treat endometrial cancer.

Engaging Community-Based Cancer Physicians: Experience of the Memorial Sloan Kettering Cancer Center Cancer Alliance.

The proliferation of relationships between community health systems and academic medical centers has created a need to identify effective components of these models. This article reports on frontline physician experiences, with one such relationship established through the Memorial Sloan Kettering Cancer Center (MSK) Cancer Alliance. MSK created the Alliance with the goals of rapidly bringing the newest standards of care into community settings and increasing patient access to clinical trials in their local communities. Alliance leadership administered a 10-question anonymous survey to physicians treating patients with cancer across the 3 Alliance member health systems: Hartford HealthCare Cancer Institute, Lehigh Valley Cancer Institute, and Miami Cancer Institute at Baptist Health South Florida. The purpose of the survey was to identify opportunities to improve physician engagement. There were 103 clinician respondents across Alliance members, of which 87 reported participation in a disease management team and were included in the final analysis. Most respondents reported high value from Alliance activities, such as attending MSK tumor boards (94%) and lecture series (96%), among those who reported them applicable. Across all respondents, most reported satisfaction with engagement opportunities, such as MSK physician participation in their institution's meetings (76%). When asked where they would like to see increased engagement, the most commonly reported response was for more lecture series (45%). Most respondents (88%) reported that the Alliance led to practice change, either for themselves or for other clinicians at their institution. Many attributed this practice change to MSK disease-specific process measures. The activities most valued by community physicians were heavily physician relationship-based. The encouraging experience of the MSK Cancer Alliance suggests that activities involving physician investment may be effective for promoting practice change in the context of cross-institution relationships. Future research is needed in this area.

Redefining Models of Childhood Cancer Survivorship Care: A Mixed-Methods Evaluation of Patient-Reported Barriers to, and Preferences for, Care

Background: As the population of children surviving cancer grows, promoting lifelong survivorship-focused care becomes increasingly important. Many survivors are disengaged from follow-up, mandating alternative models of care. To inform new models of care, we explored survivors' barriers to accessing, and preferences for, survivorship care. Methods: We invited Australian and New Zealand survivors of childhood cancer from three age groups: 25 years ('older survivors'). Participants completed questionnaires and optional interviews. We used multivariate regressions to identify associations with total reported barriers to care. Findings: 633 survivors/parents completed questionnaires: 187 parents of young survivors (mean age: 12•4 years), 251 AYAs (mean age: 20•6 years), and 195 older survivors (mean age: 32•5 years). Quantitative data was complemented by 151 in-depth interviews. Most participants, across all age groups, preferred specialized follow-up (i.e. involving oncologists, nurses or a multidisciplinary team; 86-97%). Many (36-58%) were unwilling to received community-based follow-up and 32-36% did not have a primary care physician (PCP). More parents (75%) than AYAs (58%) and older survivors (30%) were engaged in specialized follow-up. While follow-up engagement was significantly lower in older survivors, survivors' incidence of late effects increased. Of those attending a follow-up clinic, 34-56% were satisfied with their care, compared with 14-15% of those not receiving cancer-focused care (p<0•001). Commonly reported barriers included lack of awareness about follow-up availability (67%), followed by logistical (65%), belief-related (59%), and financial reasons (57%). Survivors who were older (p<0•001), lived outside a major city (p=0•008), and were further from diagnosis (p=0•014) were more likely to report a higher number of barriers to care. Interpretation: Understanding patient-reported barriers to care, and tailoring care to their follow-up preferences, may improve engagement with care and ensure that the survivorship needs of this population are met. Funding: Christina Signorelli and Joanna Fardell are supported by The Kids’ Cancer Project. Claire Wakefield is supported by a Career Development Fellowship from the NHMRC of Australia (APP1143767). The Behavioural Sciences Unit (BSU) is proudly supported by the Kids with Cancer Foundation. The BSU’s survivorship research program is funded by the Kids Cancer Alliance, The Kids’ Cancer Project and a Cancer Council NSW Program Grant (PG16-02) with the support of the Estate of the Late Harry McPaul. These funding bodies did not have any role in the study, nor did they have a role in the writing of the manuscript or the decision to submit it for publication. ANZCHOG is supported by the Australian Government, through Cancer Australia's Support for Cancer Clinical Trials program. Declaration of Interest: No author has any conflicts of interest to disclose in relation to this manuscript. Ethical Approval: Missing

Abstract 3349: Collected experiences of young-onset colorectal cancer caregivers

Abstract The Colorectal Cancer Alliance launched a survey for caregivers of young-onset colorectal cancer (CRC) patients and survivors. A caregiver of young-onset CRC is an unpaid or paid member of a person's social network who helps them with activities of daily living. Caregivers who participated in our survey (n=427) are diverse: in age, gender, and racial/ethnic group. The majority of them were between the ages of 30-39. The caregivers reported they faced many challenges including lack of resources and information on young-onset disease and the course of the disease progression. Also, many caregivers indicated they had difficulty understanding the different treatment options offered by the physicians as well as the risk and long-term side-effects associated with these aggressive treatments. Only 40 percent of providers talked to patients about genetic testing and explained to the patient's family member their elevated risk of the disease and the associated need for timely screening. The majority of caregivers (59%) reported that their loved one experienced changes in their ability to perform expected social tasks, including those of a spouse, child rearer, friend, or worker. Some caregivers also mentioned the loss of sexuality, depression, pain, despair, lack of sleep, sadness, and stress, along with a loss of faith and hope, which may cause additional strain on their relationships. Thirty-two percent of caregivers reported insufficient psychosocial (66%) and financial support (44%) to effectively care for their patients. Participants also indicated that resources such as transportation, child care, household maintenance, prevention, and surveillance information for family members are limited. Overall, about one in three caregivers reported they were missing 24 hours or more of work each month to care for their loved one. A caregiver stated she needed, “Emotional and basic help around the house with her children and someone responsible enough to stay in the house to understand what we were going through as a family.” Taken together, our survey indicates that additional resources are needed to improve the ability for caregivers to manage everyday tasks, potentially helping caregivers feel more organized and in control. The ability of caregivers to care for themselves and use tools to care for their loved ones will reduce emotional and physical demands involved with caregiving that can cause strain and burnout. The Alliance will use these survey results to learn about and track the self-reported medical, psychosocial, and quality of life experiences of this often overlooked group. Citation Format: Kimberley L. Newcomer, Ronit Yarden, Never Too Young Advisory. Collected experiences of young-onset colorectal cancer caregivers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3349.