bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract LB254: PKA signaling: a friend or foe to pediatric medulloblastoma
Authors: Kaushik Itishree , Srivastava Sanjay
Published: July 2021

Pediatric brain tumor is the leading cause of cancer-related deaths in pediatric patients ranging 0-19 years of age. Medulloblastoma is one of the most commonly occurring brain tumor in children. Sonic hedgehog (Shh) activated subgroup of medulloblastoma is considered to be highly aggressive and metastatic in nature. Recent studies and oncomine, a cancer microarray database has shown that GABAA receptor is down regulated in pediatric medulloblastoma. In this study, we have evaluated the anti-cancer effects of an anthelminthic drug ‘moxidectin' a GABAA receptor agonist. Treatment of medulloblastoma cells with moxidectin, resulted in reduced Protein kinase A (PKA) activity. Leading to the inhibition of Gli1, a major transcription factor of non-canonical Shh signaling. Moxidectin has inhibited the proliferation of Daoy, UW426, UW228, ONS76, and PFSK1 medulloblastoma cells and significantly induced apoptosis in a concentration and time dependent manner in all the cell lines. Western blotting and immunofluorescence microscopy demonstrated that moxidectin treatment significantly induced GABAA receptor expression and inhibited cAMP mediated PKA signaling. As a result, the non-canonical activation of Gli1 and its downstream effector molecules such as Pax-6, Oct-4, Sox-2 and Nanog were also inhibited by moxidectin treatment. Efficacy of moxidectin was also evaluated in subcutaneous and intracranial medulloblastoma tumor models. Our results demonstrated that daily oral administration of 2.5 mg/kg moxidectin suppressed the growth of medulloblastoma tumors by 55-70% in subcutaneous and intracranial models. Ex-vivo analysis of tumors by western blotting, IHC, TUNEL and H&E staining revealed that moxidectin suppressed medulloblastoma tumor progression by inhibiting PKA/Gli1 signaling axis indicating the significance of this pathway in medulloblastoma progression. To our knowledge, this study for the first time focuses on GABAA receptor agonist mediated PKA/Gli1 signaling inhibition. Most importantly, moxidectin is an FDA approved drug and is already in clinical use for the treatment of river blindness in humans with an established safety record, therefore any positive findings from our studies will prompt further clinical investigation into repositioning moxidectin for the treatment of MB patients.

Citation Format: Itishree Kaushik, Sanjay Srivastava. PKA signaling: a friend or foe to pediatric medulloblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB254.
Abstract ND02: BT7480: A completely novel fully tumor antigen (Nectin-4) dependent agonist of the immune cell costimulatory receptor CD137
Authors: Keen Nicholas J.
Published: July 2021

BT7480, a completely novel fully tumor antigen (Nectin-4) dependent agonist of the immune cell costimulatory receptor CD137. It is also the first example (to our knowledge) of a fully synthetic, low MW (~7.5kDa, less than 1/20th of an IgG), peptide-based approach to targeting either Nectin-4 or CD137. The costimulatory immune receptor CD137 has been recognized for its potential as a drug target in cancer alongside checkpoint inhibitors, but this promise has not been realized for patients due to toxicity (principally hepatic toxicity) and limited efficacy of current biologic based therapies. Thus, alternative approaches to this important target are warranted. Bicycles® are small, structurally constrained peptides discovered via phage display and optimized using structure-driven design and medicinal chemistry approaches. We have applied this disruptive technology to the problem, identifying CD137 binding Bicycles and chemically linking these to specific tumor antigen binding Bicycles to generate multifunctional “bi-specific” like molecules that induce tumor antigen dependent, tumor localized agonism of CD137. We termed these Tumor-targeted Immune Cell Agonists (TICAs™). BT7480 is a TICA that was designed to deliver highly potent CD137 agonism to Nectin-4 overexpressing tumor tissue. Nectin-4 is expressed at high levels in bladder, breast and lung tumors and at low levels in normal tissue and thus is an attractive target for localized immunotherapy. BT7480 binds potently to Nectin-4 expressing cells and engages CD137 expressed on immune cells in trans, leading to potent Nectin-4-dependent CD137 agonism in primary human PBMC/tumor cell co-culture assays. Treatment of Nectin-4 expressing tumors in immunocompetent mice with BT7480 induces complete tumor regressions and subsequent resistance to tumor re-challenge. Time-course examination of the treated tumors revealed a unique mechanism of action - rapid activation of myeloid cells (<24h) concomitant with a pulse of secretion of chemokines and cytokines peaking at 2-3 days, leading to a dramatic infiltration of cytotoxic T-cells on days 4-5. This is distinct from the reported behavior of checkpoint inhibitors such as PD1/PDL1 inhibitors. In the presentation we will describe the discovery work that led to the identification of BT7480, including a crystal structure of the CD137/Bicycle complex (the first reported low molecular weight ligand of this receptor), chemical optimization and structure of the molecule, it's PK and PD behavior, preliminary safety data and route to the clinic.

Citation Format: Nicholas J. Keen. BT7480: A completely novel fully tumor antigen (Nectin-4) dependent agonist of the immune cell costimulatory receptor CD137 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr ND02.
Abstract NG10: A metastasis map of human cancer cell lines
Authors: Jin Xin , Demere Zelalem , Nair Karthik , Ali Ahmed , Ferraro Gino B. , Natoli Ted , Deik Amy , Petronio Lia , Tang Andrew A. , Zhu Cong , Wang Li , Rosenberg Danny , Mangena Vamsi , Roth Jennifer , Chung Kwanghun , Jain Rakesh K. , Clish Clary B. , Heiden Matthew G. Vander , Golub Todd R.
Published: July 2021

Most deaths from cancer are explained by metastasis, and yet large-scale metastasis research has been impractical due to the inherent scale limitation of the in vivo models. Here we introduce an in vivo barcoding strategy capable of determining the metastatic potential of human cancer cell lines in murine xenografts at scale. We validated the robustness, scalability and reproducibility of the method, and applied it to 500 cell lines spanning 21 solid cancer types. We created a first-generation Metastasis Map (MetMap) that reveals organ-specific patterns of metastasis and allows relating those patterns to clinical and genomic features. We demonstrated the utility of MetMap by exploring the molecular basis of breast cancers capable of metastasizing to the brain - a principal cause of death in these patients. Breast cancers that were brain metastatic had unexpected genetic, expression, and metabolic evidence of altered lipid metabolism. Perturbing lipid metabolism curbed brain metastasis development and limited the outgrowth of cancer cells in the brain, suggesting a therapeutic strategy to combat the disease. These results illustrated the utility of MetMap as a step towards next-generation approach for high-throughput metastasis research.

Citation Format: Xin Jin, Zelalem Demere, Karthik Nair, Ahmed Ali, Gino B. Ferraro, Ted Natoli, Amy Deik, Lia Petronio, Andrew A. Tang, Cong Zhu, Li Wang, Danny Rosenberg, Vamsi Mangena, Jennifer Roth, Kwanghun Chung, Rakesh K. Jain, Clary B. Clish, Matthew G. Vander Heiden, Todd R. Golub. A metastasis map of human cancer cell lines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr NG10.
Abstract SY22-02: Personalized cancer vaccines: Antigen selection and translation into the clinic
Authors: Bhardwaj Nina
Published: July 2021

Personalized cancer vaccination targets specific cancer mutations of the individual patient's tumor, also referred to as neoantigens. Such “bespoke” vaccines are now being tested in multiple cancers and in combination with checkpoint inhibitors. This session will discuss our computational methods for antigenic epitope prediction, antigen selection (personalized and shared neoantigens derived from frame-shift mutations), validation in vitro and in vivo and future directions for the field.

Citation Format: Nina Bhardwaj. Personalized cancer vaccines: Antigen selection and translation into the clinic [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr SY22-02.
Abstract 101: The Tanzanian Pediatric Cancer Network: A Comprehensive Evaluation of the Incidence of Presenting Patients and Access to Pediatric Cancer Care in Tanzania
Authors: Maillie Luke , Mutagonda Alice , Chirande Lulu , Rehema Laiti , Jumanne Shakilu , Meleki Elton , Serventi Furaha , Alloyce Julius , Afyusisye Franco , Sanchez Sebastian , Sisk Matthew , Voeten Marie Jose , Kawira Ester , Joas Heronima , Scanlan Trish , Schroeder Kristin
Published: July 2021

Purpose: In sub-Saharan Africa, cancer treatment facilities are often scarce and centered in urban areas, which means many patients must travel long distances to reach cancer care. Still, little is known about how this distribution of cancer centers impacts patients' ability to access care.

Methods: Records of all pediatric patients (<18yo) treated for cancer in Tanzania in 2019 through the Tanzanian Pediatric Cancer Network were reviewed. This network represents all 9 hospitals currently treating children with cancer in Tanzania. Demographic and diagnostic information was recorded. ArcGIS was used to estimate patients' travel times from home addresses to cancer care. AccessMod was used to calculate 4-hour access for the population.

Results: In 2019, a total of 821 pediatric patients were diagnosed with cancer with an incidence of 1.42/100,000 population. The most common diagnoses were Wilms tumor (17.2%, n=134), retinoblastoma (16.8%, n=131), and acute lymphoblastic leukemia (15.9%, n=124). There was regional variation by diagnosis, with the Lake Zone having the highest incidence of Burkitt lymphoma (0.29; average 0.15) and retinoblastoma (0.5; average 0.33). Reported regional incidence inversely correlated to distance to cancer treatment facility. Median travel time to cancer care for patients was 4.55 hours. Currently 74.5% of the population lives within 4 hours of existing cancer care facilities, and it would require adding cancer care capacity to 8 additional facilities to reach 95% coverage.

Conclusions: This is the first comprehensive evaluation of the incidence of presenting pediatric cancer patients in Tanzania. Only 18.8% of the estimated pediatric patients with cancer in Tanzania were treated in 2019. The reported incidence was lower in areas further away from treatment centers, suggesting the importance of increased access to cancer care facilities as part of a future national scale-up strategy.

Citation Format: Luke Maillie, Alice Mutagonda, Lulu Chirande, Laiti Rehema, Shakilu Jumanne, Elton Meleki, Furaha Serventi, Julius Alloyce, Franco Afyusisye, Sebastian Sanchez, Matthew Sisk, Marie Jose Voeten, Ester Kawira, Heronima Joas, Trish Scanlan, Kristin Schroeder. The Tanzanian Pediatric Cancer Network: A Comprehensive Evaluation of the Incidence of Presenting Patients and Access to Pediatric Cancer Care in Tanzania [abstract]. In: Proceedings of the 9th Annual Symposium on Global Cancer Research; Global Cancer Research and Control: Looking Back and Charting a Path Forward; 2021 Mar 10-11. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2021;30(7 Suppl):Abstract nr 101.
Abstract 24: Compliance with Referral for Evaluation of Breast Abnormalities among HIV-Clinic Patients in Eswatini
Authors: O'Neil Daniel , Nxumalo Sifiso , Ngcamphalala Cebisile , Tharp G , Jacobson Judith , Nuwagaba-Biribonwoha Harriet , Dlamini Xolisile , Neugut Alfred , Harris Tiffany
Published: July 2021

Purpose: Women living with HIV (WLHIV) are living longer and are at increasing risk for breast cancer (BC). Earlier detection of BC is essential to reduce late-stage diagnosis and BC mortality in sub-Saharan Africa, the region most heavily impacted by HIV. We implemented a pilot BC early detection program in Eswatini HIV clinics and studied patients' compliance with referral for evaluation of breast abnormalities.

Methods: Nurses at five Eswatini HIV clinics were trained to ask all WLHIV aged ≥18 years about breast symptoms, to offer clinical breast exam (CBE) to symptomatic women, and to refer for further evaluation if appropriate. Referred, consenting patients completed baseline demographic questionnaires and questionnaires at 30- and 60-days post-enrollment, regarding referral outcomes. We used chi-squared testing to identify patient characteristics associated with completing referral.

Results: From June 2019-April 2020, 9,502 WLHIV were screened for breast symptoms: 150 (1.6%) underwent CBE; 93 (62.0%) of those were referred for further evaluation; and 90 (96.7%) were enrolled in the evaluation. Of enrolled WLHIV, median age was 39 (range: 20-65) years, 54 (61.0%) reported completing referral. Referral completion was not associated with age, employment status, relationship status, or various prior experiences related to BC (all p>0.05). Of those who completed referral, 42 (80.7%) reported having no illness identified, 3 (5.8%) reported a new BC diagnosis, 1 (1.9%) reported a breast abscess, and 6 (11.5%) were still undergoing evaluation; diagnosis was missing for 2. The most common reasons cited for not completing referral were cost of transport or care, conflicting employment-related commitments, other conflicting commitments, and the breast clinic not accommodating the patient upon presentation.

Conclusion: In this pilot BC screening program, 60% of WLHIV completed referral for further evaluation. Efforts to improve compliance with referral could focus on reducing the time and cost entailed by obtaining specialized breast care.

Citation Format: Daniel O'Neil, Sifiso Nxumalo, Cebisile Ngcamphalala, G Tharp, Judith Jacobson, Harriet Nuwagaba-Biribonwoha, Xolisile Dlamini, Alfred Neugut, Tiffany Harris. Compliance with Referral for Evaluation of Breast Abnormalities among HIV-Clinic Patients in Eswatini [abstract]. In: Proceedings of the 9th Annual Symposium on Global Cancer Research; Global Cancer Research and Control: Looking Back and Charting a Path Forward; 2021 Mar 10-11. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2021;30(7 Suppl):Abstract nr 24.
Abstract 28: Steroid Hormone Biosynthesis Metabolism Is Associated with Fatigue Related to Androgen Deprivation Therapy for Prostate Cancer
Authors: Allen Hannah , Feng Li Rebekah , Saligan Leorey
Published: July 2021

Purpose: Androgen deprivation therapy (ADT) is a common and effective treatment for prostate cancer. However, multiple adverse effects such as fatigue are associated with this therapy. The purpose of this study was to characterize the metabolic profile associated with cancer-related fatigue specific to ADT.

Methods: 160 participants with non-metastatic prostate cancer who were receiving (+ADT, n = 58) or were not receiving neoadjuvant ADT (-ADT), n = 102) before undergoing radiotherapy were included in this study. Plasma samples were taken from all participants, and metabolites were identified and quantified using ultrahigh performance liquid chromatography/mass spectrometry. Partial least square discriminant analysis was used to identify discriminant metabolite features, and diagnostic performance of selected classifiers was quantified using AUROC curve analysis. Pathway enrichment analysis was performed using metabolite sets enrichment analyses.

Results: Particular metabolic pathways were found to be significantly over-represented in the +ADT group compared to the -ADT group, thereby creating a distinct metabolic profile associated with each group. These pathways were steroid hormone biosynthesis pathways, including androstenedione metabolism and androgen and estrogen metabolism, as well as amino acid metabolism, glutathione metabolism, and carnitine synthesis. Of all these pathways, steroid hormone biosynthesis was most significantly correlated with fatigue severity. It was also found that sleep-related impairment was highly correlated with severity of fatigue and inversely correlated with ADT-induced reduction in androsterone sulfate.

Conclusion: Individuals who received ADT reported significantly higher levels of fatigue. This finding may be due to sleep-related impairment associated with changes in steroid hormone biosynthesis. This result paves the way for future research on cancer-related fatigue and changes in sleep patterns due to alterations in steroid hormones. It may also help patients and clinicians make a more precise cost-benefit analysis when deciding on a prostate cancer treatment plan.

Citation Format: Hannah Allen, Li Rebekah Feng, Leorey Saligan. Steroid Hormone Biosynthesis Metabolism Is Associated with Fatigue Related to Androgen Deprivation Therapy for Prostate Cancer [abstract]. In: Proceedings of the 9th Annual Symposium on Global Cancer Research; Global Cancer Research and Control: Looking Back and Charting a Path Forward; 2021 Mar 10-11. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2021;30(7 Suppl):Abstract nr 28.
Abstract 37: Enhancing Cancer Diagnostics through Provision of Pathology Support for Hospitals in Low and Middle-Income Countries: A Case of International Cancer Institute (ICI), Kenya
Authors: Kitur Gloria , Achieng Emmah , Gitau George , Asirwa Chite
Published: July 2021

Purpose: Delays in diagnosis and treatment of cancers in low-and-middle-income countries (LMICs) attributable to provider and/or systemic factors are linked to poor patient outcomes. Pathology services are not available in most lower level facilities hence, there's delayed diagnosis and initiation of treatment for cancers. There is also limited availability of specialized pathology tests.

Methods: International Cancer Institute (ICI), conducts joint clinics and cancer screening with partner counties where same-day screening and on-site biopsing is conducted after which samples for cytology, histology and/or histochemistry are sent for processing in the ICI diagnostics and research laboratory at a subsidized cost with a turn-around-time for results being 14 days or less. Results get discussed virtually by a multi-disciplinary team (MDT) of both ICI and the outreach site and positive results are singled out for further diagnostics like computerized tomography (CT) scan and blood work ups.

Results: Between September and December 2020, a total of 146 samples for Cytology; 197 biopsy samples for histology and 66 samples for immunohistochemistry were shipped to the ICI Diagnostics and research laboratory from five ICI Outreach sites namely: Kisumu, Taita Taveta, Meru & Makueni counties and Sori Lakeside Hospital. In less than 28 days from date of screening, the MDT discussed positive results and gave recommendations; results were disseminated to outreach sites for patient counseling and drawing of treatment plans; and appropriate treatment was initiated at the outreach sites in established cancer clinics run jointly by ICI and the counties. The ICI Consultant Pathologist and Histotechnologist provide further technical support and consultation to the clinic team when necessary.

Conclusion: Better patient outcomes are assured when there is reduced turn-around time from screening to diagnosis and initiation of treatment for cancers in LMICs. Accessibility of pathology services through strengthening of existing health systems can be achieved through multi-sectoral partnerships.

Citation Format: Gloria Kitur, Emmah Achieng, George Gitau, Chite Asirwa. Enhancing Cancer Diagnostics through Provision of Pathology Support for Hospitals in Low and Middle-Income Countries: A Case of International Cancer Institute (ICI), Kenya [abstract]. In: Proceedings of the 9th Annual Symposium on Global Cancer Research; Global Cancer Research and Control: Looking Back and Charting a Path Forward; 2021 Mar 10-11. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2021;30(7 Suppl):Abstract nr 37.
Abstract 40: Pathology Training for Cancer Diagnosis in Africa: Perspectives from Two Virtual Courses
Authors: Seymour Daniel , Graef Katy , Iliyasu Yawale , Diomande Mohenou Isidore Jean-Marie , Jaquet Samuel , Kelly Melissa , Soles Ryan , Milner Dan
Published: July 2021

Purpose: The burden of cancer continues to grow in Africa, yet there are too few trained pathologists to manage the rising number of cancer cases. The shortage of resources in African countries, as well as the travel restrictions resulting from the COVID-19 pandemic, necessitate innovative means of training and supporting pathologists across the continent. In response to requests for training in cancer pathology, two virtual training courses were organized: one conducted in English for participants in Nigeria and another conducted in French for participants across several countries in Francophone Africa. Each course had weekly 90-minute sessions covering essential topics in cancer pathology led by global experts.

Methods: Two research questions were investigated for both courses: 1) did the participants improve their knowledge of the topics covered during the course? and 2) did the course participants appreciate the virtual training format?

Results: The Nigeria course enrolled 85 participants from 26 Nigerian states, while the Francophone Africa course enrolled 425 participants from 18 African countries. On the post course survey, 95.8% of Nigeria course respondents and 96.1% of Francophone Africa respondents reported being satisfied or very satisfied with the course's virtual format. In the pre-post technical assessment, participants increased their scores on average by 3.4% (p>0.05) in the Nigeria course and by 13.1% (p<0.001) in the Francophone Africa course.

Conclusion: Virtual training is a promising tool to improve cancer diagnosis in Africa, as the experience of the two courses illustrates participants appreciate the virtual format. However, continued training and mentorship are required to reinforce new skills and enable the participants to appropriately apply their new knowledge to their daily practice.

Citation Format: Daniel Seymour, MPA, Katy Graef, PhD, Yawale Iliyasu, MD, Mohenou Isidore Jean-Marie Diomande, MD, Samuel Jaquet, MD, Melissa Kelly, PhD, Ryan Soles, Dan Milner, MD, MSc, MBA. Pathology Training for Cancer Diagnosis in Africa: Perspectives from Two Virtual Courses [abstract]. In: Proceedings of the 9th Annual Symposium on Global Cancer Research; Global Cancer Research and Control: Looking Back and Charting a Path Forward; 2021 Mar 10-11. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2021;30(7 Suppl):Abstract nr 40.
Abstract 43: Global Burden of Cancer in 2020 Attributable to Alcohol Consumption: A Population-Based Study
Authors: Rumgay Harriet , Shield Kevin , Charvat Hadrien , Ferrari Pietro , Sornpaisarn Bundit , Obot Isidore , Islami Farhad , Lemmens Valery , Rehm Jürgen , Soerjomataram Isabelle
Published: July 2021

Purpose: Alcohol use is causally linked to multiple cancer sites. We present global, regional and national estimates of alcohol-attributable cancer burden in 2020 to inform alcohol policy and cancer control across different settings globally.

Methods: In this population-based study, we calculated population attributable fractions (PAFs) using relative risk estimates and alcohol use prevalence by age, sex, and country. Assuming a 10-year latency period between alcohol consumption and cancer occurrence, we used alcohol consumption prevalence from 2010 and GLOBOCAN 2020 data to estimate new cancer cases attributable to alcohol consumption. We also calculated the contribution of moderate (<20 g alcohol per day), risky (20 to 60 g per day), and heavy (>60 g per day) drinking to the total alcohol-attributable cancer burden.

Results: Globally, an estimated 702 900, or 3.9%, of all new cases of cancer in 2020 were attributable to alcohol consumption. Males represented 71.1% of the total alcohol-attributable cancer cases. The cancer sites which contributed the most alcohol-attributable cases were cancers of the esophagus (183 000 cases), liver (142 600 cases), and breast (114 300 cases). PAFs were lowest in Northern Africa and Western Asia (less than 1%) in both sexes, and highest in Eastern Asia (7.7%) and Central and Eastern Europe (6.9%) in men, and in Central and Eastern Europe (3.8%), Western Europe (3.5%) and Australia and New Zealand (3.55%) in women. Risky and heavy drinking contributed most to the burden of alcohol-attributable cancers (42.6% and 42.5%, respectively), and moderate drinking contributed 14.9%.

Conclusion: Our findings highlight the need for effective policy and interventions to increase awareness of cancer risks associated with alcohol use and decrease overall alcohol consumption to avoid future rises in alcohol-attributable cancer burden in several regions of the world.

Citation Format: Harriet Rumgay, Kevin Shield, Hadrien Charvat, Pietro Ferrari, Bundit Sornpaisarn, Isidore Obot, Farhad Islami, Valery Lemmens, Jürgen Rehm, Isabelle Soerjomataram. Global Burden of Cancer in 2020 Attributable to Alcohol Consumption: A Population-Based Study [abstract]. In: Proceedings of the 9th Annual Symposium on Global Cancer Research; Global Cancer Research and Control: Looking Back and Charting a Path Forward; 2021 Mar 10-11. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2021;30(7 Suppl):Abstract nr 43.
Abstract 44: Global Incidence of Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma in 2018
Authors: Rumgay Harriet , Ferlay Jacques , de Martel Catherine , Georges Damien , Ibrahim Amal Samy , Zheng Rongshou , Wei Wenqiang , Lemmens Valery , Soerjomataram Isabelle
Published: July 2021

Purpose: The two main subtypes of primary liver cancer are hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). We aimed to produce worldwide and regional estimates of the distribution of these subtypes based on high quality data.

Methods: Population-based cancer registry data were used to compute sex-specific proportions of HCC, iCCA, and other specified histology. The proportions were applied to sex- and age-specific liver cancer estimates from GLOBOCAN 2018 and age-standardized incidence rates were calculated.

Results: Of an estimated 826,000 cases of liver cancer in 2018, 661,000 (80.0%) were HCC, 123,000 (14.9%) were iCCA and 42,000 (5.1%) were other specified histology. In nearly all world regions, HCC was more common than iCCA, except in women in Northern Europe where iCCA was more common than HCC. The highest rates of HCC were found in Eastern Asia (14.8 cases per 100,000 person-years), Northern Africa (13.2) and South-Eastern Asia (9.5). The highest rates of iCCA were in South-Eastern Asia (2.9), Eastern Asia (2.0), Northern Europe, the Caribbean and Central America, and Oceania (all 1.8). HCC was more often diagnosed in males (M:F rate ratio ranged from 1.6 to 5.0), while the sex difference in iCCA rates was much smaller (M:F between 0.7 and 1.7).

Conclusion: Uncovering the distinct patterns of HCC and iCCA by sex, country and world region is critical to further develop public health policy to reduce liver cancer burden and monitor progress in controlling the disease globally. Improved completeness of liver cancer histology registration would provide more reliable estimates for policymakers to base decisions on.

Citation Format: Harriet Rumgay, Jacques Ferlay, Catherine de Martel, Damien Georges, Amal Samy Ibrahim, Rongshou Zheng, Wenqiang Wei, Valery Lemmens, Isabelle Soerjomataram. Global Incidence of Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma in 2018 [abstract]. In: Proceedings of the 9th Annual Symposium on Global Cancer Research; Global Cancer Research and Control: Looking Back and Charting a Path Forward; 2021 Mar 10-11. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2021;30(7 Suppl):Abstract nr 44.
Abstract 47: Survival of Breast Cancer in Women Treated Under Mexico's Seguro Popular
Authors: Bandala-Jacques Antonio , Huerta-Gutierrez Rodrigo , Zamora-Muñoz Salvador , Cabrera Paula , Mohar Alejandro , Lajous Martin
Published: July 2021

Purpose: To determine 5-year survival for breast cancer among uninsured women treated under Mexico's Seguro Popular landmark health reform according to clinical stage and identify factors associated to survival.

Methods: We conducted a retrospective cohort study with data obtained from national reimbursement claims of patients treated under Seguro Popular from January 2007 to December 2016. Reimbursement data was cross-linked with a national mortality registry. We used the Kaplan-Meier method to estimate overall survival according to different variables and stratified them by clinical stage as early (I-IIA), locally advanced (IIB-IIIC), and metastatic (IV). We explored the relation between age, hospital patient volume, hospital infrastructure, and mortality. Hazard ratios and 95% confidence intervals (95%CI) were estimated, using the Cox proportional hazards model to adjust for clinical stage.

Results: A total of 57,175 patients with breast cancer were analyzed. The mean age was 43.4 (SD 12.4). Most patients had locally advanced disease at diagnosis (55.1%, n=31,559) and 9.5% (n=5,435) had metastatic disease. The distribution of clinical stage did not appear to change over time (11% in 2007 vs. 13% in 2015 for metastatic disease). Five-year survival was 88.9% (CI95% 88.3-89.5) for early-stage disease, 69.6% (CI95% 69-70.2) for locally advanced cancer, and 36.9% (CI95% 35.4-38.5) for metastatic disease. These survival estimates did not change over time. After adjustment for clinical stage, age <40 years old (HR 1.17 [CI95% 1.12-1.23]), low hospital patient volume (≤248 patients/year, HR 1.21 [CI95% 1.17-1.25]), and treatment at a locally funded hospital (HR 1.15 [CI95% 1.11-1.2]) were associated with higher mortality.

Conclusions: While Seguro Popular provided access to treatment for breast cancer, a high proportion of women were treated at advanced stages and clinical stage at diagnosis and survival did not appear to change over a decade. Future programs should prioritize early detection and strengthen quality of care.

Citation Format: Antonio Bandala-Jacques, Rodrigo Huerta-Gutierrez, Salvador Zamora-Muñoz, Paula Cabrera, Alejandro Mohar, Martin Lajous. Survival of Breast Cancer in Women Treated Under Mexico's Seguro Popular [abstract]. In: Proceedings of the 9th Annual Symposium on Global Cancer Research; Global Cancer Research and Control: Looking Back and Charting a Path Forward; 2021 Mar 10-11. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2021;30(7 Suppl):Abstract nr 47.
Abstract 48: Characterization of Human Papillomavirus (HPV) Sequence and Integration and Analysis of Immune Response Genes for Application in Guatemalan Cervical Cancer
Authors: Rossi Nicole , Dean Michael
Published: July 2021

Purpose: Cervical cancer is a significant cause of mortality in Guatemala due to inefficient screening and late diagnosis. We are developing new technologies to improve the analysis of HPV-positive cervical tumors in Guatemala. The goal is to enhance understanding of HPV infection, tumor progression, and therapeutics development.

Methods: We established a cohort of 700 Guatemalan cervical cancer patients with blood, fresh-frozen tumors, and clinical data. To optimize techniques, we extracted DNA and RNA from 20 cervical cancer cell lines. Long-read whole genome and transcriptome sequencing, and long-range PCR, were performed on cervical cancer DNA. HPV and HLA gene sequences were aligned to reference genomes.

Results: Complete HPV sequences were compiled, HPV subtypes determined, and integration sites identified in cell lines with single and multiple integration events. HLA types of the class I genes were determined from the complete gene sequence, mutations detected, and HLA homozygosity. RNA was used for long-read whole transcriptome analysis of HPV and cellular genes. These results establish the use of long-read sequencing technology to characterize both HLA and host genomes. Paired Guatemalan tumor and blood DNA was successfully used for full HLA gene sequencing and mutation analysis. In addition, the complete HPV genome sequence was resolved. Binding of HPV peptides was predicted using the HPV and HLA sequences. These peptides identify the specific HPV epitopes potentially presented on the cell surface.

Conclusion: Long-read RNA and DNA sequencing technology allow the determination of the complete HPV sequence, integration, and HLA class I typing and mutation analysis. HLA typing provides essential information on an individual's immune response. These techniques and analyses are being applied to tumor samples from women in Guatemala to aid in the development of targeted treatments. These methods are portable and could be employed in low- and middle-income countries.

Citation Format: Nicole Rossi, Michael Dean. Characterization of Human Papillomavirus (HPV) Sequence and Integration and Analysis of Immune Response Genes for Application in Guatemalan Cervical Cancer [abstract]. In: Proceedings of the 9th Annual Symposium on Global Cancer Research; Global Cancer Research and Control: Looking Back and Charting a Path Forward; 2021 Mar 10-11. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2021;30(7 Suppl):Abstract nr 48.
Abstract 51: Breast Biopsy Report Abstraction Process From A Community And Hospital Based Screening And Treatment Programme In A Lmic (Kenya) Between January 2017 – December 2019
Authors: Maina Stephen Karuru , Achieng Emmah , Elias Hussein , Kibor Kibet , Asirwa Chite
Published: July 2021

Purpose: There is no standardized way of reporting the pathological lab results therefore there is inadequate reporting in Low- and Middle-Income Countries like Kenya. Proper documentation of the lab results is key in providing appropriate care to breast cancer patients, policymaking, designing, implementing, and evaluating cancer control activities. There is need to standardize reporting of the pathological breast cancer lab results.

Methods: The biopsy results for all the Africa Breast and Cervical Cancer Program (ABCCP) in Kenya patients seen between the year 2017 to 2019 were received, photocopied, and filed in box files. Biopsy reporting was done by various pathologists within the country. To standardize the reporting, a data abstraction questionnaire was developed from Protocol for the Examination of Resection Specimens From Patients With Invasive Carcinoma of the Breast (7th Edition, 2012) adapted from the American College of Pathologists programmed into an Open Data Kit. Raw abstracted data was verified against corresponding images to identify misclassifications by the consultant. Sensitivity and specificity for correct classification by the clinical and non-clinical research assistants was calculated and evaluated.

Results: A total of 1490 records were abstracted in 3 weeks, out of which 529 records were breast biopsy results. On average, the research assistants abstracted 83 (42 - 195) records. The research assistants were able to correctly classify 284 cases as malignant and 202 cases as benign with a Sensitivity of 92% and Specificity of 92%. Upon review of the data by the consultant, the total misclassified records were 18 benign classified as malignant and 25 malignant cases classified as benign. There was no statistically significant difference (p = 0.1125) in the classifications between the clinical and non-clinical abstraction staff.

Conclusion: There was high sensitivity and specificity on correctly classifying the biopsy results for both well trained clinical and non-clinical staff.

Citation Format: Stephen Karuru Maina, Emmah Achieng, Hussein Elias, Kibet Kibor, Chite Asirwa. Breast Biopsy Report Abstraction Process From A Community And Hospital Based Screening And Treatment Programme In A Lmic (Kenya) Between January 2017 – December 2019 [abstract]. In: Proceedings of the 9th Annual Symposium on Global Cancer Research; Global Cancer Research and Control: Looking Back and Charting a Path Forward; 2021 Mar 10-11. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2021;30(7 Suppl):Abstract nr 51.
Abstract 58: Serum Based Exosomal miRNAs as in Novel Biomarkers for the Initial Prediction of Early-Stage Lung Cancer
Authors: Patel Nishant , Zhang Haijun , Ren Lili
Published: July 2021

Purpose: Currently focuses on the identification of early-stage lung cancer (ESLC) is the core of the prevention and treatment of lung cancer, which is desperately needed throughout the world to improve lung cancer survival. Our study has primarily aimed at exosome-derived miRNAs in the detection of ESLC and discrimination between Benign lung nodules(BLN) and Healthy individuals. We aim to determine sensitive and specific liquid biopsy-based biomarkers in tackling ESLC.

Methods: Discovering the non-invasive serum exosomal based miRNAs (sEXO-miRNAs) biomarkers through next-generation sequencing (NGS)in 9 participants (ESLC-3, BLN-3 and Healthy-3) and validated by 143 (ESLC-46, BLN-46 and Healthy-51) recruiters via RT-PCR in a cohort of Zhongda Hospital affiliated to the medical school of Southeast University, Nanjing, China.

Results: By doing NGS, we have discovered 769 differently expressed miRNAs mutual between the three groups. Amid those miRNAs, we have selected the topmost highly up-or down-regulated significant sEXO-miRNAs as biomarkers following certain threshold and statistical criteria, which were sEXO-miR-424-5p, sEXO-miR-512-5p, and sEXo-miR-1271-5p for subsequent validation in 3 groups of a single-center cohort. The area under the receiver operating curve (AUC-ROC) of 3 individual miRNAs in between three groups ranged from 0.633 to 0.995 (95%CI: 0.515~1.000 ranged, p<0.0274~p<0.0001) in the validation cohort. Overall in the ESLC vs BLN group, the combination of the three sEXO-miRNAs'AUC was 0.824 (95%CI: 0.738~0.909, p<0.0001) whereas sensitivity, specificity, PPV, NPV and accuracy were 77.08%, 79.55%, 80.43%, 76.09% and 78.26% respectively by logistic regression analysis.

Conclusion: Our study discovered significant three differentials expressed sEXO-miRNAs (hsa-miR-424-5p, hsa-miR-512-5p, and hsa-miR-1271-5p), and validated throughout in between ESLC, BLN and healthy individuals. These sEXO-miRNAs provided substantial diagnostic efficacy towards predicting ESLC and accurately discriminate with BLN and healthy recruiters. Therefore, our novel sEXO-miRNAs as biomarkers for prior detection ESLC is quite promising in clinical practice and can be used for precision-based diagnosing purposes.

Citation Format: Nishant Patel, Haijun Zhang, Lili Ren. Serum Based Exosomal miRNAs as in Novel Biomarkers for the Initial Prediction of Early-Stage Lung Cancer [abstract]. In: Proceedings of the 9th Annual Symposium on Global Cancer Research; Global Cancer Research and Control: Looking Back and Charting a Path Forward; 2021 Mar 10-11. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2021;30(7 Suppl):Abstract nr 58.
Abstract 59: Examining a Culturally Relevant Intervention to Promote Colorectal Cancer Screening in Egypt
Authors: Bateman Lori Brand , Nawwar Ahmed , Khamess Somaia , Fouad Mona N. , Arafat Waleed , Abdelmoneim Salah-Eldin , Bae Sejong , Falkner Katie , Rogers Laura Q. , Scarinci Isabel
Published: July 2021

Purpose: Colorectal cancer (CRC) incidence and mortality rates continue to climb in Egypt and other low- and middle-income countries, where few screening intervention programs exist. In Egypt, CRC screening is not a routine part of preventive care and most CRC diagnoses happen with advanced disease and poor prognosis. This pilot study aims to develop, implement, and examine the feasibility of a culturally relevant intervention to promote CRC screening among healthy adults in Alexandria, Egypt.

Methods: This feasibility study was conducted in two clinics in Alexandria, Egypt in December 2019-March 2020. Participants were individuals age 50 and above who were visiting the clinics. Medical students were trained to recruit patients, increase awareness on the importance of CRC screening, and provide a voucher and instructions for returning a guaiac fecal occult blood test (gFOBT) kit. Students followed up with phone call reminders to return the kit, report results, and encourage participants with abnormal results to receive further no-cost testing. Our outcome measure was the number of total participants returning the gFOBT kit. We hypothesized that 20% of patients who received the intervention would return the kits, assuming a null screening rate of 2% and target screening rate after the intervention of 20%. A sample size of 120 would achieve 99% power to detect a difference of 18% at a 1% significance level.

Results: Of the 117 patients who were recruited, 44 patients (37.6%) returned a kit, with 95% exact confidence interval of (28.8, 47.0). Of the 44 patients who returned a kit, five (11.4%) had a positive FOBT test, with 95% exact confidence interval of (3.8, 24.6). Of these five patients, three (60%) followed up with colonoscopy.

Conclusion: This feasibility study provides promising findings to lay the foundation for a larger pragmatic trial that would address barriers to CRC screening in Egypt

Citation Format: Lori Brand Bateman, Ahmed Nawwar, Somaia Khamess, Mona N. Fouad, Waleed Arafat, Salah-Eldin Abdelmoneim, Sejong Bae, Katie Falkner, Laura Q. Rogers, Isabel Scarinci. Examining a Culturally Relevant Intervention to Promote Colorectal Cancer Screening in Egypt [abstract]. In: Proceedings of the 9th Annual Symposium on Global Cancer Research; Global Cancer Research and Control: Looking Back and Charting a Path Forward; 2021 Mar 10-11. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2021;30(7 Suppl):Abstract nr 59.
Abstract 60: Cancer Navigator: A Video-Based Support and Education Tool for Cancer Patients and Their Caregivers
Authors: Pedraza-Flechas Ana , Taylor Carolyn , Barrera-Suárez Erika , Perez Luis , Soto Jesica , Arias Alejandra , Patiño Andres , Perales Vera , Pinzón-Rondon Ángela , Ruíz-Sternberg Ángela , Cabanes Anna , Le Phuongthao
Published: July 2021

Purpose: The aim of this study was to identify the informational needs of cancer patients and caregivers among a diverse population in Colombia to inform the development of Cancer Navigator, a video-based tool to help cancer patients and their families understand and navigate their treatment.

Methods: Seven focus group discussions (FGDs) with n=47 participants and n=80 in-depth interviews (IDIs) were conducted to understand the needs of cancer patients and caregivers regarding their cancer diagnosis, treatment and rehabilitation in the Colombian healthcare system. The information was analyzed using thematic analysis, and informed the development of a series of 18 short infographic and personal narrative videos covering different cancer topics, delivered by local clinicians and survivors; along with a resource guide of local services for food, housing and transportation. A pilot study was conducted to evaluate pre-post depression and anxiety among 22 caregivers and 18 cancer patients at Hospital Méderi (Bogotá, Colombia).

Results: Themes/topics identified from the interviews included: treatment effects; cancer etiology; nutrition, physical activity recommendations; psychological/spiritual/emotional support; alternative therapies; warning signs; self-learning cancer tools and administrative procedures. The pilot study showed a mild decrease in anxiety and distress immediately after viewing three videos. The proportion of patients with anxiety levels above normal (>7 on Hospital Anxiety and Depression Scale, HADS) changed from 27% to 15% after viewing (p=0.17), and distress (score >5 on the distress thermometer) decreased from 35% to 22% (p=0.22).

Conclusion: The Cancer Navigator video-based educational/support tool shows promise for reducing anxiety and distress among cancer patients and caregivers in Colombia. Next steps will be to test the feasibility and acceptability of the videos among patients, caregivers and healthcare providers at three additional oncology hospitals in Bogotá in 2021.

Citation Format: Ana Pedraza-Flechas, Carolyn Taylor, Erika Barrera-Suárez, Luis Perez, Jesica Soto, Alejandra Arias, Andres Patiño, Vera Perales, Ángela Pinzón-Rondon, Ángela Ruíz-Sternberg, Anna Cabanes, Phuongthao Le. Cancer Navigator: A Video-Based Support and Education Tool for Cancer Patients and Their Caregivers [abstract]. In: Proceedings of the 9th Annual Symposium on Global Cancer Research; Global Cancer Research and Control: Looking Back and Charting a Path Forward; 2021 Mar 10-11. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2021;30(7 Suppl):Abstract nr 60.
Abstract 65: Early Assessment of the Pandemic Effects on Cancer Screening Services: The International Cancer Screening Network COVID-19 Survey
Authors: Puricelli Perin Douglas M. , Elfström K. Miriam , Broeders Mireille J. M.
Published: July 2021

Purpose: Screening, when effectively implemented, can decrease the burden of breast, cervical, colorectal and lung cancers. As COVID-19 became a pandemic in March 2020, cancer screening practitioners globally reported the suspension of cancer screening and diagnostic as part of the emergency response. The International Cancer Screening Network (ICSN) implemented a survey to capture the details and consequences of decisions to suspend cancer screening services and understand the global effects of the COVID-19 pandemic on cancer screening.

Methods: A 33-question survey was sent out to 882 email addresses to gather general information about the settings and assess the decision-making process that led to cancer screening suspension (or not). Furthermore, information regarding communication with stakeholders and impact on resources and patient follow-up was collected. Quantitative data have been analyzed as general frequencies overall and by setting, while a comment section under each survey item captured more nuanced information.

Results: Responses from the 98 participants that completed the full survey (12%) were categorized into 66 individual settings representing 35 countries. Most settings are organized screening programs (82%, n=54), and suspended cancer screening services (91%, n=60) around March 2020 (68%, n=45), guided by a government decision (77%, n=51). Few settings made their decision about whether to suspend services following a preparedness plan (26%, n=17). Professionals were reassigned (62%, n=41) and infrastructure repurposed (53%, n=35) in most places, and 39% (n=26) saw most follow up visits delayed.

Conclusion: COVID-19 pandemic has had important effects on cancer screening services worldwide, including the suspension of cancer screening in most settings. Most cancer screening services were not prepared to deal with the scale of the pandemic but have shown great flexibility in supporting the response. This survey will inform the next steps for assessing the longer-term impact of COVID-19 on cancer screening.

Funding statement: Funded by the NCI Contract No. HHSN261200800001E75N910D00024, Task Order No. 75N91019F00129 (D.M.P.P.).

Citation Format: Douglas M. Puricelli Perin, K. Miriam Elfström, Mireille J. M. Broeders. Early Assessment of the Pandemic Effects on Cancer Screening Services: The International Cancer Screening Network COVID-19 Survey [abstract]. In: Proceedings of the 9th Annual Symposium on Global Cancer Research; Global Cancer Research and Control: Looking Back and Charting a Path Forward; 2021 Mar 10-11. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2021;30(7 Suppl):Abstract nr 65.