bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparing an Intermittent Fasting Intervention With a Continuous Energy Restriction Intervention On Weight Loss in Community-Based Black Adults
Authors: Yeary KH , Yu H , Yao S , Johnson D , Harris N , Dauphin C , Saad-Harfouche F , DiCarlo E
Published: June 2023

Introduction: Compared to other racial/ethnic groups, Blacks have the highest rates of obesity, a well-established risk factor for some cancers. Continuous caloric energy restriction (CER) interventions consist of small reductions in daily caloric intake and are recommended by government agencies to treat obesity. However, these interventions are difficult to adhere to and cause less weight loss in Blacks compared to Whites. Intermittent fasting (IF), which can consist of eating 25% of one's daily calorie intake per day on some days and ad libitum intake on other days, causes the same amount of weight loss as CER interventions. IF may be easier for participants to adhere to and may lower cancer risk and prognosis to a greater extent than can be attributed to weight loss alone. However, most IF studies have been conducted with White participants, and have provided participants with standardized meals and/or nutrition counseling not readily available in real-world situations. Thus, the purpose of our study is to test the effect of IF interventions in diverse groups outside of controlled settings. Methods: We are comparing a 6-month CER intervention with a 6-month IF intervention on weight loss in Black adults using a blinded randomized controlled comparative effectiveness trial. Trained community health workers are delivering the interventions. Six churches (anticipated n = 60) were randomized to either intervention. Staff blinded to treatment condition are collecting anthropometric, 3-day dietary food recall, and survey data at baseline and 6-month follow-up. Results: To date, four churches (n = 29) have completed baseline and follow-up assessments. Most participants were female (82.6%) with a mean age of 57.9 years. There were significant within group differences, with both IF and CER participants losing 3.2% (4.4) and 2.8% (4.5), respectively, of their body weight from baseline to 6-month follow-up. Conclusion: This is the first study to test an IF intervention designed for community-based Black adults in a 'real-world' setting. If proven effective, this IF intervention has the potential to serve as an alternative to CER interventions for weight loss and cancer risk reduction in minority populations.
Data from Efficacy of Osimertinib in Patients with Lung Cancer Positive for Uncommon EGFR Exon 19 Deletion Mutations
Authors: Grant Michael J. , Aredo Jacqueline V. , Starrett Jacqueline H. , Stockhammer Paul , van Alderwerelt van Rosenburgh Iris K. , Wurtz Anna , Piper-Valillo Andrew J. , Piotrowska Zofia , Falcon Christina , Yu Helena A. , Aggarwal Charu , Scholes Dylan , Patil Tejas , Nguyen Christina , Phadke Manali , Li Fang-Yong , Neal Joel , Lemmon Mark A. , Walther Zenta , Politi Katerina , Goldberg Sarah B.
Published: June 2023

AbstractPurpose:
The uncommon EGFR exon 19 deletion (ex19del), L747_A750>P, demonstrates reduced sensitivity to osimertinib compared with the common ex19del, E746_A750del in preclinical models. The clinical efficacy of osimertinib in patients with non–small cell lung cancer harboring L747_A750>P and other uncommon ex19dels is not known.
Experimental Design:
The AACR GENIE database was interrogated to characterize the frequency of individual ex19dels relative to other variants, and a multicenter retrospective cohort was used to compare clinical outcomes for patients with tumors harboring E746_A750del, L747_A750>P, and other uncommon ex19dels who received osimertinib in the first line (1L) or in second or later lines of therapy and were T790M+ (≥2L).
Results:
ex19dels comprised 45% of EGFR mutations, with 72 distinct variants ranging in frequency from 28.1% (E746_A750del) to 0.03%, with L747_A750>P representing 1.8% of the EGFR mutant cohort. In our multi-institutional cohort (N = 200), E746_A750del was associated with significantly prolonged progression-free survival (PFS) with 1L osimertinib versus L747_A750>P [median 21.3 months (95% confidence interval, 17.0–31.7) vs. 11.7 months (10.8–29.4); adjusted HR 0.52 (0.28–0.98); P = 0.043]. Osimertinib efficacy in patients with other uncommon ex19dels varied on the basis of the specific mutation present.
Conclusions:
The ex19del L747_A750>P is associated with inferior PFS compared with the common E746_A750del mutation in patients treated with 1L osimertinib. Understanding differences in osimertinib efficacy among EGFR ex19del subtypes could alter management of these patients in the future.
Data from Type 2 diabetes mellitus and efficacy outcomes from imune checkpoint blockade in patients with cancer
Authors: Cortellini Alessio , D'Alessio Antonio , Cleary Siobhan , Buti Sebastiano , Bersanelli Melissa , Bordi Paola , Tonini Giuseppe , Vincenzi Bruno , Tucci Marco , Russo Alessandro , Pantano Francesco , Russano Marco , Stucci Luigia Stefania , Sergi Maria Chiara , Falconi Martina , Zarzana Maria Antonietta. , Santini Daniele , Spagnolo Francesco , Tanda Enrica T. , Rastelli Francesca , Giorgi Francesca Chiara. , Pergolesi Federica , Giusti Raffaele , Filetti Marco , Lo Bianco Francesca , Marchetti Paolo , Botticelli Andrea , Gelibter Alain , Siringo Marco , Ferrari Marco , Marconcini Riccardo , Vitale Maria Giuseppa. , Nicolardi Linda , Chiari Rita , Ghidini Michele , Nigro Olga , Grossi Francesco , De Tursi Michele , Di Marino Pietro , Queirolo Paola , Bracarda Sergio , Macrini Serena , Inno Alessandro , Zoratto Federica , Veltri Enzo , Spoto Chiara , Vitale Maria Grazia. , Cannita Katia , Gennari Alessandra , Morganstein Daniel L. , Mallardo Domenico , Nibid Lorenzo , Sabarese Giovanna , Brunetti Leonardo , Perrone Giuseppe , Ascierto Paolo A. , Ficorella Corrado , Pinato David J.
Published: June 2023

Abstract
Purpose: No evidence exists as to whether type 2 diabetes (T2DM) impairs clinical outcome from Immune Checkpoint Inhibitors (ICI) in patients with solid tumors. Experimental Design: In a large cohort of ICI recipients treated at 21 institutions from June 2014 to June 2020, we studied whether patients on glucose lowering medications (GLM) for T2DM had shorter OS and PFS. We used targeted transcriptomics in a subset of patients to explore differences in the tumor microenvironment of patients with/without diabetes. Results: A total of 1395 patients were included. Primary tumors included NSCLC (54.7%), melanoma (24.7%), renal cell (15.0%) and other carcinomas (5.6%). Following multivariable analysis, patients on GLM (n=226, 16.2%) displayed an increased risk of death (HR 1.29, 95%CI:1.07-1.56) and disease progression/death (HR 1.21, 95%CI:1.03-1.43) independent of number of GLM received. We matched 92 metformin exposed with 363 controls and 78 patients on other oral GLM or insulin with 299 control patients. Exposure to metformin, but not other GLM was associated with an increased risk of death (HR 1.53, 95%CI:1.16-2.03) and disease progression/death (HR 1.34, 95%CI:1.04-1.72). T2DM patients with higher pre-treatment glycaemia had higher neutrophil-to-lymphocyte ratio (p=0.04), while exploratory tumoral transcriptomic profiling in a subset of patients (n=22) revealed differential regulation of innate and adaptive immune pathways in T2DM patients. Conclusions: In this study patients on GLM experienced worse outcomes from immunotherapy, independent of baseline features. Prospective studies are warranted to clarify the relative impact of metformin over a pre-existing diagnosis of T2DM in influencing poorer outcomes in this population.
Supplementary Methods from Identification of a First-in-Class Small-Molecule Inhibitor of the EIF4E-RBM38 Complex That Enhances Wild-type TP53 Protein Translation for Tumor Growth Suppression
Authors: Lucchesi Christopher A. , Zhang Jin , Gao Mingchun , Shaw Jared , Chen Xinbin
Published: June 2023

Small molecule synthesis
Figure S4 from Antitumor Immune Mechanisms of the Anti-Complement Factor H Antibody GT103
Authors: Bushey Ryan T. , Saxena Ruchi , Campa Michael J. , Gottlin Elizabeth B. , He You-Wen , Patz Edward F.
Published: June 2023

Gating strategy for detection of ADCP.
Figure S2 from Antitumor Immune Mechanisms of the Anti-Complement Factor H Antibody GT103
Authors: Bushey Ryan T. , Saxena Ruchi , Campa Michael J. , Gottlin Elizabeth B. , He You-Wen , Patz Edward F.
Published: June 2023

Deposition of intratumoral C3dg and C3d.
Data from BET inhibition sensitizes immunologically-cold Rb-deficient prostate cancer to immune checkpoint blockade
Authors: Olson Brian M. , Chaudagar Kiranj , Bao Riyue , Saha Sweta Sharma. , Hong Christina , Li Marguerite , Rameshbabu Srikrishnan , Chen Raymond , Thomas Alison , Patnaik Akash
Published: June 2023

Abstract
Non-T cell-inflamed immunologically “cold” tumor microenvironments (TME) are associated with poor responsiveness to immune checkpoint blockade (ICB), and can be sculpted by tumor cell genomics. Here we evaluated how Retinoblastoma (Rb) tumor suppressor loss of function (LOF), one of the most frequent alterations in human cancer and associated with lineage plasticity, poor prognosis and therapeutic outcomes, alters the TME, and whether therapeutic strategies targeting the molecular consequences of Rb loss enhance ICB efficacy. We performed bioinformatics analysis to elucidate the impact of endogenous Rb LOF on the immune TME in human primary and metastatic tumors. Next, we utilized isogenic murine models of Rb-deficient prostate cancer (PC) for in vitro and in vivo mechanistic studies to examine how Rb loss and bromodomain and extraterminal (BET) domain inhibition (BETi) reprograms the immune landscape, and evaluated in vivo therapeutic efficacy of BETi, singly and in combination with ICB and androgen deprivation therapy. Rb loss was enriched in non-T cell-inflamed tumors, and Rb-deficient murine tumors demonstrated decreased immune infiltration in vivo. The BETi JQ1 increased immune infiltration into the TME through enhanced tumor cell STING/NF-κB activation and type I interferon (IFN) signaling within tumor cells, resulting in differential macrophage and T cell-mediated tumor growth inhibition and sensitization of Rb-deficient PC to ICB. BETi can reprogram the immunologically cold Rb-deficient TME via STING/NF-κB/IFN signaling to sensitize Rb-deficient PC to ICB. These data provide the mechanistic rationale to test combinations of BETi and ICB in clinical trials of Rb-deficient PC.
Data from BET Inhibition Sensitizes Immunologically Cold Rb-Deficient Prostate Cancer to Immune Checkpoint Blockade
Authors: Olson Brian M. , Chaudagar Kiranj , Bao Riyue , Saha Sweta Sharma , Hong Christina , Li Marguerite , Rameshbabu Srikrishnan , Chen Raymond , Thomas Alison , Patnaik Akash
Published: June 2023

Abstract
Non–T-cell–inflamed immunologically “cold” tumor microenvironments (TME) are associated with poor responsiveness to immune checkpoint blockade (ICB) and can be sculpted by tumor cell genomics. Here, we evaluated how retinoblastoma (Rb) tumor-suppressor loss-of-function (LOF), one of the most frequent alterations in human cancer and associated with lineage plasticity, poor prognosis, and therapeutic outcomes, alters the TME, and whether therapeutic strategies targeting the molecular consequences of Rb loss enhance ICB efficacy. We performed bioinformatics analysis to elucidate the impact of endogenous Rb LOF on the immune TME in human primary and metastatic tumors. Next, we used isogenic murine models of Rb-deficient prostate cancer for in vitro and in vivo mechanistic studies to examine how Rb loss and bromodomain and extraterminal (BET) domain inhibition (BETi) reprograms the immune landscape, and evaluated in vivo therapeutic efficacy of BETi, singly and in combination with ICB and androgen deprivation therapy. Rb loss was enriched in non–T-cell–inflamed tumors, and Rb-deficient murine tumors demonstrated decreased immune infiltration in vivo. The BETi JQ1 increased immune infiltration into the TME through enhanced tumor cell STING/NF-κB activation and type I IFN signaling within tumor cells, resulting in differential macrophage and T-cell–mediated tumor growth inhibition and sensitization of Rb-deficient prostate cancer to ICB. BETi can reprogram the immunologically cold Rb-deficient TME via STING/NF-κB/IFN signaling to sensitize Rb-deficient prostate cancer to ICB. These data provide the mechanistic rationale to test combinations of BETi and ICB in clinical trials of Rb-deficient prostate cancer.
Data from Identification of a First-in-Class Small Molecule Inhibitor of the eIF4E-RBM38 Complex that Enhances wild-type p53 Protein Translation for Tumor Growth Suppression
Authors: Lucchesi Christopher A. , Zhang Jin , Gao Mingchun , Shaw Jared , Chen Xinbin
Published: June 2023

Abstract
eIF4E, an mRNA cap-binding protein, is necessary for cap-dependent translation. Overexpression of eIF4E is known to promote cancer development by preferentially translating a group of oncogenic mRNAs. Thus, 4EGI-1, a disruptor of eIF4E-eIF4G interaction, was developed to inhibit oncoprotein expression for cancer therapy. Interestingly, RBM38, an RNA-binding protein, interacts with eIF4E on p53 mRNA, prevents eIF4E from binding to p53 mRNA cap, and inhibits p53 expression. Thus, Pep8, an eight amino acid peptide derived from RBM38, was developed to disrupt the eIF4E-RBM38 complex, leading to increased p53 expression and decreased tumor cell growth. Herein, we have developed a first-in-class small molecule compound 094, which interacts with eIF4E via the same pocket as does Pep8, dissociates RBM38 from eIF4E, and enhances p53 translation in RBM38- and eIF4E-dependent manners. Structure-activity relationship (SAR) studies identified that both the fluorobenzene and ethyl benzamide are necessary for compound 094 to interact with eIF4E. Further, we showed that compound 094 is capable of suppressing 3D tumor spheroid growth in RBM38- and p53-dependent manners. Additionally, we found that compound 094 cooperates with chemotherapeutic agent doxorubicin and eIF4E inhibitor 4EGI-1 to suppress tumor cell growth. Collectively, we showed that two distinct approaches can be used together to target eIF4E for cancer therapy by enhancing wild-type p53 expression (094), and by suppressing oncoprotein expression (4EGI-1).
Data from Identification of a First-in-Class Small-Molecule Inhibitor of the EIF4E-RBM38 Complex That Enhances Wild-type TP53 Protein Translation for Tumor Growth Suppression
Authors: Lucchesi Christopher A. , Zhang Jin , Gao Mingchun , Shaw Jared , Chen Xinbin
Published: June 2023

Abstract
EIF4E, an mRNA cap-binding protein, is necessary for cap-dependent translation. Overexpression of EIF4E is known to promote cancer development by preferentially translating a group of oncogenic mRNAs. Thus, 4EGI-1, a disruptor of EIF4E-EIF4G1 interaction, was developed to inhibit oncoprotein expression for cancer therapy. Interestingly, RBM38, an RNA-binding protein, interacts with EIF4E on TP53 mRNA, prevents EIF4E from binding to TP53 mRNA cap, and inhibits TP53 expression. Thus, Pep8, an eight amino acid peptide derived from RBM38, was developed to disrupt the EIF4E-RBM38 complex, leading to increased TP53 expression and decreased tumor cell growth. Herein, we have developed a first-in-class small-molecule compound 094, which interacts with EIF4E via the same pocket as does Pep8, dissociates RBM38 from EIF4E, and enhances TP53 translation in RBM38- and EIF4E-dependent manners. Structure-activity relationship studies identified that both the fluorobenzene and ethyl benzamide are necessary for compound 094 to interact with EIF4E. Furthermore, we showed that compound 094 is capable of suppressing three-dimensional tumor spheroid growth in RBM38- and TP53-dependent manners. In addition, we found that compound 094 cooperates with the chemotherapeutic agent doxorubicin and EIF4E inhibitor 4EGI-1 to suppress tumor cell growth. Collectively, we showed that two distinct approaches can be used together to target EIF4E for cancer therapy by enhancing wild-type TP53 expression (094) and by suppressing oncoprotein expression (4EGI-1).
Data from Antitumor Immune Mechanisms of the Anti-Complement Factor H Antibody GT103
Authors: Bushey Ryan T. , Saxena Ruchi , Campa Michael J. , Gottlin Elizabeth B. , He You-Wen , Patz Edward F.
Published: June 2023

Abstract
Development of novel therapeutic antibodies that not only kill tumor cells but modulate the adaptive immune response has the potential to produce long term anti-cancer immunity and a durable clinical response. We previously reported the discovery of anti-complement factor H (CFH) autoantibodies in lung cancer patients that were associated with early stage disease and exceptional outcomes. The human monoclonal antibody GT103, produced from a single CFH autoantibody-expressing B cell of a lung cancer patient, recognizes a conformationally distinct epitope on tumor cells, kills tumor cells, and inhibits tumor growth in animal studies. Recent experiments have shown that GT103 restructures the tumor microenvironment and initiates a robust antitumoral adaptive immune response. The current study further elucidates several mechanisms by which GT103 kills tumor cells and drives the immune program. Here we show GT103 has specificity for tumor cells without binding to native soluble CFH or normal tissues. GT103 causes complement C3 split product deposition on tumor cells in vitro and in vivo, triggers antibody-dependent cellular phagocytosis, and increases translocation of the danger associated molecular pattern molecule calreticulin to the plasma membrane. We also demonstrate that GT103 causes B cell activation in vitro and in vivo, and that GT103 antitumor activity in vivo is B cell dependent. The complex mechanism of GT103, a tumor specific antibody that kills tumor cells and stimulates an immune response, supports further development of this human-derived antibody as a novel therapeutic option for patients with lung cancer.
Data from Antitumor Immune Mechanisms of the Anti-Complement Factor H Antibody GT103
Authors: Bushey Ryan T. , Saxena Ruchi , Campa Michael J. , Gottlin Elizabeth B. , He You-Wen , Patz Edward F.
Published: June 2023

Abstract
Development of novel therapeutic antibodies that not only kill tumor cells but modulate the adaptive immune response has the potential to produce long term anticancer immunity and a durable clinical response. We previously reported the discovery of anti-complement factor H (CFH) autoantibodies in patients with lung cancer that were associated with early-stage disease and exceptional outcomes. The human mAb GT103, produced from a single CFH autoantibody-expressing B cell of a patient with lung cancer, recognizes a conformationally distinct epitope on tumor cells, kills tumor cells, and inhibits tumor growth in animal studies. Recent experiments have shown that GT103 restructures the tumor microenvironment and initiates a robust antitumoral adaptive immune response. The current study further elucidates several mechanisms by which GT103 kills tumor cells and drives the immune program. Here we show GT103 has specificity for tumor cells without binding to native soluble CFH or normal tissues. GT103 causes complement C3 split product deposition on tumor cells in vitro and in vivo, triggers antibody-dependent cellular phagocytosis, and increases translocation of the danger-associated molecular pattern molecule calreticulin to the plasma membrane. We also demonstrate that GT103 causes B-cell activation in vitro and in vivo, and that GT103 antitumor activity in vivo is B-cell dependent. The complex mechanism of GT103, a tumor-specific antibody that kills tumor cells and stimulates an immune response, supports further development of this human-derived antibody as a novel therapeutic option for patients with lung cancer.
Abstract 27: Demographic Factors Associated with Extracutaneous Involvement in Kaposi Sarcoma
Authors: Swedek Michelle , Wu Xinxin , Silberstein Peter , Vardell Victoria
Published: June 2023

Purpose: Kaposi sarcoma (KS) is a soft tissue tumor that typically presents with red or purple skin lesions. However, extracutaneous involvement can occur in severe disease. The National Cancer Database (NCDB) compiles data from 1,400 cancer programs across the United States; to our knowledge, there has yet to be a study in the NCDB comparing demographic features and presentation of KS with cutaneous versus extracutaneous disease. Thus, there is a need to characterize the KS cohort with regards to primary site.

Methods: We conducted a retrospective analysis of the NCDB from 2004 to 2019 for Kaposi sarcoma patients (n=5,587). Analysis was completed between patients with cutaneous (n=3,963) and extracutaneous (n=1,624) involvement using Pearson Chi-square and t-tests. Survival was estimated using Kaplan-Meier curves.

Results: Non-cutaneous lesions made up 29.1% of diagnoses and primarily included connective/subcutaneous tissue (12.2%), as well as digestive organs (4.1%). Median survival was lower in the extracutaneous (101.7 months) cohort compared to cutaneous (131.5 months) cohort (p<0.001). Women were more likely to present with non-cutaneous lesions compared to men (37.3% versus 27.6%, p<0.001). Spanish/Hispanic subjects were less likely to have extracutaneous involvement compared to non-Spanish/Hispanic subjects (p=0.006). Patients at academic centers were less likely to have extracutaneous lesions compared to other facilities (p<0.001). Residing in the Central United States was associated with increased incidence of extracutaneous disease (p<0.001). Patients with extracutaneous disease lived further from the reporting hospital (23.95 miles) compared to patients with cutaneous (16.24 miles) involvement (p=0.004). There was no significant difference in mean age between cutaneous (58.41 years) and non-cutaneous (57.97 years) cohorts. No clear trend existed between race, insurance status, education, or income in relation to extracutaneous disease.

Conclusion: To our knowledge, our study is the first to compare demographic features and trends associated with cutaneous and extracutaneous KS in the NCDB. We revealed that extracutaneous primary site is associated with poorer survival and highlighted several significant differences between the cohorts.

Citation Format: Michelle Swedek, Xinxin Wu, Peter Silberstein, Victoria Vardell. Demographic Factors Associated with Extracutaneous Involvement in Kaposi Sarcoma [abstract]. In: Proceedings of the 11th Annual Symposium on Global Cancer Research; Closing the Research-to-Implementation Gap; 2023 Apr 4-6. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(6_Suppl):Abstract nr 27.
Abstract 32: Epidemiological Characteristics and Histopathologic Patterns Cranial-Spinal Tumours (CSTs) at Bugando Medical Centre (BMC) in the Lake Zone Region of Mwanza Tanzania in a Period of 8 Years
Authors: Lubuulwa James , Schroeder Kristin
Published: June 2023

Purpose: To understand the epidemiological characteristics and histopathologic patterns cranial-spinal tumours (CSTs) at Bugando Medical Centre (BMC) in the lake zone region of Mwanza Tanzania

Methods: Patients who underwent biopsy (surgery for excision or incision of lesion) for different CSTs between January 2014 and June 2022 at BMC with valid histopathologic results were included in a retrospective database. Patients who had clinical and radiological diagnosis of central nervous system tumours without histopathological biopsy and patients who had primary biopsy not taken at our institution were excluded. Collected data included basic demographics, clinical presentation and histopathologic findings. Report on surgical outcomes and prognosis and mortality was not included due to lack of consistency in recordings and the retrospective nature on the study.

Results: A total of 123 cranial spinal tumors in 63 (52.1%) males and 59 (47.1%) female patients were recorded. Pediatric and adult patients accounted for 35.8% and 64.2% of the cases, respectively. The predominant age group affected was between 40 and 49 years (23.5%). The most common histopathological diagnosis in the present study was meningioma (26%), followed by astrocytic tumors (13.8%), metastatic tumors (8.1%), lymphomas (5.7%) and medulloblastomas (5.7%). The meningothelial meningioma was the most common type of meningioma (48.5%). Glioblastoma Multiforme accounted for 35% of the astrocytic tumors.

Conclusion: This retrospective study established a baseline profile of brain tumors based primarily on the histopathological experience at a tertiary care hospital in the lake zone region of Mwanza Tanzania and provides an initiating platform to workup for future population targeted studies on cranial spinal tumors.

Citation Format: James Lubuulwa, Kristin Schroeder. Epidemiological Characteristics and Histopathologic Patterns Cranial-Spinal Tumours (CSTs) at Bugando Medical Centre (BMC) in the Lake Zone Region of Mwanza Tanzania in a Period of 8 Years [abstract]. In: Proceedings of the 11th Annual Symposium on Global Cancer Research; Closing the Research-to-Implementation Gap; 2023 Apr 4-6. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(6_Suppl):Abstract nr 32.
Abstract 44: Hispanic Liver Cancer Patients are Underrepresented in Phase III Clinical Trials Conducted in the Last 10 Years
Authors: Monge Cecilia , Greten Tim , McGlynn Katherine , Maldonado Alberto
Published: June 2023

Purpose: Hispanics bear the largest burden of liver cancer and are currently the largest subpopulation after non-Hispanic Whites in the United States (US). We aim to further characterize this burden and the inclusion of Hispanics in multinational phase III advanced liver cancer clinical trials.

Methods and Results: Amongst the ten most common types of cancer in the US; we analyzed which cancer had the highest relative frequency in Hispanics compared to non-Hispanic Whites (NHW). We obtained the percentages of Hispanic individuals affected by liver cancer through the National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results Program and used the Center for Disease Control and Prevention (CDC), United States Cancer Statistics (USCS) as a second database for comparison. We performed a database search using PubMed, Embase, and Web of Science: Core Collection to identify phase III clinical trials studying advanced liver cancer in the last 10 years and collected information about enrollment of Hispanic patients.

A total of 13113 patients were included in phase III multinational clinical trials studying liver cancer in the last ten years. The percentage of Hispanic patients was 1.63%, 1.34% of the trial participants were NHB, 31.06 % were NHW and 46.89 % were Asian; while 32.1% had unknown racial/ethnic characteristics. However, from 2012 to 2019 the proportion HCC and BTC occurring in Hispanics was 23.2% and 22.6% respectively.

Conclusions: Hispanics are disproportionately affected by liver cancer and are underrepresented in multinational phase III clinical trials in the last ten years despite having the highest relative incidence rates among the three major racial/ethnic groups in the US.

Citation Format: Cecilia Monge, Tim Greten, Katherine McGlynn, Alberto Maldonado. Hispanic Liver Cancer Patients are Underrepresented in Phase III Clinical Trials Conducted in the Last 10 Years [abstract]. In: Proceedings of the 11th Annual Symposium on Global Cancer Research; Closing the Research-to-Implementation Gap; 2023 Apr 4-6. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(6_Suppl):Abstract nr 44.
Abstract 55: Insurance Status and Surgical Cancer Patient Characteristics and Outcomes at Muhimbili National Hospital in Dar Es Salaam Tanzania
Authors: Brand Nathan , Emanual Obedi , Boeck Marissa , Akoko Larry
Published: June 2023

Purpose: Cancer is a leading cause of death among adults in Tanzania. Surgery plays a vital role in the diagnosis, treatment, and palliation of malignancies. Laparotomy is a common surgical approach for abdominal cancer pathologies in Tanzania where access to minimally invasive surgery is limited. We aimed to understand the characteristics and laparotomy outcomes of patients with abdominal organ cancer at Muhimbili National Hospital (MNH), the National Referral Hospital in Dar es Salaam Tanzania.

Methods: We conducted a prospective observational cohort study of all patients over the age of 18 undergoing laparotomy at MNH from August 1st 2022-December 22nd 2022. Patients were consented and followed during their index and, if applicable, re-admission hospitalization(s), and were contacted 30-days post discharge by telephone. Cancer diagnosis was made via the operative report by the operative surgeon. Staging and final pathology was not routinely collected.

Results: Overall, 246 patients underwent laparotomy during the study period. Of those patients, 109 (44%) were diagnosed with cancer. Of the patients with cancer, 54 (50%) were male and the median age was 59 (IQR 45, 65). Insurance status was known in 101 patients and 64 (63%) were insured. Of those with insurance, 57 (89%) were covered by the National Health Insurance Fund. Uninsured patients were significantly more likely to present for an emergency operation versus insured patients (24% vs. 8%, p=0.02). In addition, insurance status was an independent risk factor for death within 30 days post-operatively after controlling for age, sex, evidence of pre-operative sepsis, American Society of Anesthesiologists physical status classification, and emergency versus scheduled surgery (OR 5.5, CI 1.4-22).

Conclusion: Access to medical and surgical services is vital for a country’s national cancer control strategy. At the National Referral Hospital in Tanzania, uninsured cancer patients are more likely to present for emergency surgery, suggesting limited access to care for these vulnerable patients. In addition, being uninsured is independently associated with increased 30-day perioperative mortality, highlighting the need to expand insurance coverage to ensure all cancer patients in Tanzania have equal access to care throughout their treatment course to achieve equitable outcomes.

Citation Format: Nathan Brand, Obedi Emanual, Marissa Boeck, Larry Akoko. Insurance Status and Surgical Cancer Patient Characteristics and Outcomes at Muhimbili National Hospital in Dar Es Salaam Tanzania [abstract]. In: Proceedings of the 11th Annual Symposium on Global Cancer Research; Closing the Research-to-Implementation Gap; 2023 Apr 4-6. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(6_Suppl):Abstract nr 55.
Abstract 80: The Impact of Covid-19 Pandemic in Colonoscopies and Colorectal, Rectosigmoid and Anal Cancer Screening
Authors: de Andrade Rafaela , Lech Gabriele Eckerdt , Barreto Pedro Antonio Paludo Menna , Alberti Arthur Minas , Beltramo Luiza Seixas de Sá , Azambuja Fernando , da Silva Laura Tibola Marques , Kieling Lucas , Silveira Pedro Arthur Zimmer
Published: June 2023

Purpose: Colorectal, rectosigmoid and anal cancer are responsible for the death of around 20,000 people in Brazil every year. Those types of cancer typically have a slow evolution, around 10 years. Thus, colonoscopies performed periodically are an important tool in the early detection of early neoplasms, increasing the survival rate. With the advent of the Covid-19 pandemic, many procedures considered non-urgent were canceled, such as colonoscopies for cancer screening, which left thousands of patients unattended.

Methods: This is a descriptive analysis and data was collected from the DATASUS database, relating the number of colorectal, rectosigmoid and anus cancer diagnoses and performed colonoscopies among Brazilian regions in the years of 2019 and 2020.

Results: In 2019, 347,098 colonoscopies were performed in Brazil and 36,326 people were diagnosed with colorectal, rectosigmoid or anus cancer. On the other hand, in 2020, only 241,329 colonoscopies were performed, meaning a 30,4% reduction in the number of procedures. However, 36.274 people were diagnosed with colorectal, rectosigmoid or anus cancer.

Conclusion: With the advent of Covid-19 pandemic in 2020, many patients lost their connection with their hospitals and the constancy of carrying out tests, making screening and early detection of possible cancer a hard task. Although the number of diagnoses in 2020 did not have a significant drop, the decrease of more than 30% in the number of colonoscopies in that same year will have impacts not yet accounted for on the diagnoses of colorectal, rectosigmoid and anal cancers, since these cancers have a slow development. In view of this situation, solutions that recover the damned exams patients of the pandemic must be implemented so that cancer patients have a chance of treatment and cure.

Citation Format: Rafaela de Andrade, Gabriele Eckerdt Lech, Pedro Antonio Paludo Menna Barreto, Arthur Minas Alberti, Luiza Seixas de Sá Beltramo, Fernando Azambuja, Laura Tibola Marques da Silva, Lucas Kieling, Pedro Arthur Zimmer Silveira. The Impact of Covid-19 Pandemic in Colonoscopies and Colorectal, Rectosigmoid and Anal Cancer Screening [abstract]. In: Proceedings of the 11th Annual Symposium on Global Cancer Research; Closing the Research-to-Implementation Gap; 2023 Apr 4-6. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(6_Suppl):Abstract nr 80.
Abstract 87: Time From Symptom Development to Care Milestones at the Only Public Oncology Clinic in Belize
Authors: Wong Wayne , Dickerson James , Habet Martha , Bernard Margaret , Kelly Lorna , Lattin John , Garrity Philip , Huang Franklin , Yacab Ramon
Published: June 2023

Purpose: Belize is a middle-income Caribbean country with a fragmented healthcare system. In 2018, the first and only public medical oncology clinic was opened through a capacity building partnership with the Ministry of Health. Little is known about the country’s referral infrastructure for cancer. Here we report on the stage at presentation to the clinic, and the time from symptom development to various care milestones (biopsy, oncology clinic visit, chemo, upfront surgery), referred to as time-to-care, to establish a base timeline.

Methods: We performed a retrospective review of available data at the Karl Heusner Memorial Hospital (KHMH) oncology clinic from 2018 - 2022, gathering cancer type, stage, and the dates of care milestones (biopsy, initial clinic visit, chemo, upfront surgery). Date of symptom development was consistently documented by the treating physician (RY).

Results: The most common presenting malignancies (n=465) were breast (28%), cervical (12%), hematologic (8%), and colorectal (7%). For staged patients (n=352), the most common presentations were stage III (28%) and IV (40%). For time-to-care, patients with available data (n=208) were seen for an initial oncology clinic visit a median of 180 days (IQR 87-382) after self-reported symptom development. For time-to-chemo at any site (ex. Belize, Mexico, Guatemala), the median was 189 days (IQR 108-404). For upfront surgery at any site the median was 188 days (IQR 60-352). In contrast to these long lead times, once established at the KHMH clinic, the time from the initial oncology clinic visit to a biopsy (if not done previously) was 22 days (IQR 11-47, n=42), 18 days (IQR 5-60, n=115) to begin chemo, and 40 days (IQR 24-72, n=22) to surgery.

Conclusion: Patients were seen at the KHMH oncology clinic with predominantly late stage disease around six months after symptoms started. This is a higher fraction of stage III/IV disease than previously reported in Central America. Understanding drivers of these delays will allow for the creation of targeted public health interventions. As a marker that building infrastructure in Belize is possible, the partnership between the Belizean government and hospital administration has netted time-to-care intervals comparable to high-income nations.

Citation Format: Wayne Wong, James Dickerson, Martha Habet, Margaret Bernard, Lorna Kelly, John Lattin, Philip Garrity, Franklin Huang, Ramon Yacab. Time From Symptom Development to Care Milestones at the Only Public Oncology Clinic in Belize [abstract]. In: Proceedings of the 11th Annual Symposium on Global Cancer Research; Closing the Research-to-Implementation Gap; 2023 Apr 4-6. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(6_Suppl):Abstract nr 87.
Abstract 89: Translation and Linguistic Validation of the Mastectomy Module of the BREAST-Q Questionnaire for Use in Nigeria
Authors: Olasehinde Olalekan , Romanoff Anya
Published: June 2023

Purpose: The majority of breast cancer patients in sub-Saharan Africa are recommended to have mastectomy; The impact of mastectomy on a predominantly young African patient population requires evaluation. The BREAST-Q is a validated patient-reported outcome measure of quality-of-life following breast surgery that has been translated into 30 languages-none in Africa. This study aimed to translate and validate the mastectomy module of the BREAST-Q for use in Nigeria.

Methods: The BREAST-Q mastectomy module was translated from English to Yoruba (a major Nigerian language) and linguistically validated using best practice guidelines. Translation was performed in 4 steps: forward translation (x 2), back translation, back translation review, and cognitive interviews with post-mastectomy patients. The translated BREAST-Q instrument was administered to post-mastectomy patients (n=21) alongside the EORTC-QLQ BR23 to evaluate construct validity.

Results: The translation process identified phrases not amenable to direct translation, including “emotionally healthy” and descriptions of pain (“nagging,” “throbbing,” “sharp”). Translations were amended to reflect local context and question intent. Patients provided suggestions to simplify complex phrases, such as “discomfort in your breast area.”during cognitive interviews. Internal consistency within scales was over the 0.70 threshold for psychosocial wellbeing (α=0.84-0.87), sexual wellbeing (α =0.98-0.99), physical wellbeing in chest (α =0.84-0.86), and satisfaction with care (α =0.89-0.93). ICC for test-retest reliability was moderate (0.46-0.63).

Conclusion: The Yoruba version of the BREAST-Q mastectomy module in Yoruba presents a conceptually equivalent version in a language that is easy to understand.. We will use this validated instrument in a pilot study of Nigerian patients to identify targets for intervention to improve the patient experience and compliance with breast cancer surgery.

Citation Format: Olalekan Olasehinde, Anya Romanoff. Translation and Linguistic Validation of the Mastectomy Module of the BREAST-Q Questionnaire for Use in Nigeria [abstract]. In: Proceedings of the 11th Annual Symposium on Global Cancer Research; Closing the Research-to-Implementation Gap; 2023 Apr 4-6. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(6_Suppl):Abstract nr 89.
Abstract 96: When Canada is a Under-Resourced Country: Patient-Oriented Research on Optimizing Rational Decision-Making for Bladder Cancer
Authors: Frank Erica
Published: June 2023

Purpose: To identify gaps between the ideal and current approaches to Non-Muscle Invasive Bladder Cancer (NMIBC) in Canada, and determine what should be done short- and long-term to address those gaps.

Methods: Prompted by a patient diagnosed with NMIBC in July 2022, we first searched the global literature for the most-effective preventive, screening, diagnostic, and therapeutic approaches to NMIBC, and also examined sites such as Bladder Cancer Canada and professional societies’ sites for clinical recommendations. We next conducted written and oral interviews with urologists, researchers, primary care physicians, and manufacturers of related interventions to understand and synthesize the literature and determine the best clinical course of action.

Results: Our approach produced prompt and free care, of quality ranging from poor to outstanding. It required substantial patient resilience and advocacy, much of which is likely easily remediable, some of which will require policy changes. Care quality gaps of particular concern that were identified included:

Conclusion: Treatment of NMIBC in Canada is not currently provided in an optimized or rational fashion. Several improvements that are without meaningful associated cost have been identified that we conclude should be immediately implemented. Other interventions should be considered immediately by policymakers to reduce unnecessary morbidity, mortality, suffering, and other societal costs.

Citation Format: Erica Frank. When Canada is a Under-Resourced Country: Patient-Oriented Research on Optimizing Rational Decision-Making for Bladder Cancer [abstract]. In: Proceedings of the 11th Annual Symposium on Global Cancer Research; Closing the Research-to-Implementation Gap; 2023 Apr 4-6. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(6_Suppl):Abstract nr 96.
Abstract 97: Who Gets Diagnosed Later? Demographic Differences in Early Vs. Late-Stage Medullary Thyroid Carcinoma: A NCDB Analysis
Authors: Keirns Darby , Hsia Beau , Silberstein Peter , Wu Xinxin
Published: June 2023

Purpose: Medullary thyroid cancer (MTC) is a less common cancer of the thyroid. Earlier diagnosis is associated with better survival and patient outcomes with less treatment. This study evaluates how various demographic factors impact the stage of MTC at diagnosis.

Methods: 9,652 patients with MTC were analyzed within the National Cancer Database (NCDB) between the years 2004-2020. Demographics between those with early (I) or late-stage (IV) disease were compared including sex, race, Hispanic origin, primary insurance payer, median income, percentage with a high school degree, and facility type. Multivariate binary logistic regression analysis was performed with SPSS version 28 with a significance level of p < 0.05.

Results: Female patients were 68% less likely to be diagnosed with late-stage MTC than male patients (p=<0.001; 95% CI= [0.283-0.356]). Patients with an income >$63,000 were 23% less likely to be diagnosed with late-stage MTC than those with an income <$38,000 (p=0.024; 95% CI= [0.613-0.967]). Those with private insurance, Medicaid, Medicare, and other government insurance were less likely (65%, 57%, 67%, and 61% respectively) to be diagnosed with late-stage MTC compared with those who were uninsured (private insurance: p=<0.001; 95% CI= [0.241-0.510], Medicaid: p=<0.001; 95% CI= [0.284-0.655], Medicare: p=<0.001; 95% CI= [0.226-0.486], other government insurance: p=0.004; 95% CI= [0.210-0.744]). Patients treated at Integrated Network Cancer Programs (INCP) and Comprehensive Community Cancer Programs (CCCP) are less likely to be diagnosed with late-stage MTC than Academic/Research Programs (21% and 18% respectively), with no significant difference found with Community Cancer Programs (INCP: p=0.002; 95% CI= [0.674-0.917], CCCP: p=0.004; 95% CI= [0.717-0.940]). No significant difference was found between race, Hispanic origin, or percentage with a high school degree.

Conclusions: Patients who are male, uninsured, have low socioeconomic status, or are treated at Academic/Research Programs are more likely to be diagnosed later than their counterparts. This data demonstrates demographics that may influence whether a patient is diagnosed with a favorable, early-stage MTC or a late-stage MTC that results in worsened outcomes. Identifying these possible inequities contributes to a greater understanding of social determinants of health. Literature on such inequities can be used to advocate for better care for our cancer patients.

Citation Format: Darby Keirns, Beau Hsia, Peter Silberstein, Xinxin Wu. Who Gets Diagnosed Later? Demographic Differences in Early Vs. Late-Stage Medullary Thyroid Carcinoma: A NCDB Analysis [abstract]. In: Proceedings of the 11th Annual Symposium on Global Cancer Research; Closing the Research-to-Implementation Gap; 2023 Apr 4-6. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(6_Suppl):Abstract nr 97.
Figure S6 from Interdependence of SS18-SSX–driven YAP1 and β-Catenin Activation in Synovial Sarcoma
Authors: Isfort Ilka , Berthold Ruth , Heinst Lorena , Wardelmann Eva , Larsson Olle , Trautmann Marcel , Hartmann Wolfgang
Published: June 2023

Figure S6 shows that the mutual activation of YAP1/TAZ and β-catenin in SySa cells is impeded by knockdown of BAF complex subunits.
Figure S3 from Interdependence of SS18-SSX–driven YAP1 and β-Catenin Activation in Synovial Sarcoma
Authors: Isfort Ilka , Berthold Ruth , Heinst Lorena , Wardelmann Eva , Larsson Olle , Trautmann Marcel , Hartmann Wolfgang
Published: June 2023

Figure S3 shows a reciprocal regulation of YAP1/TAZ-TEAD and β-catenin-TCF in SySa cells via luciferase assays.
Supplementary Figures 1 - 12, Supplementary Tables 1-5 from BLEACH&STAIN 15-marker Multiplexed Imaging in 3,098 Human Carcinomas Reveals Six Major PD-L1–driven Immune Phenotypes with Distinct Spatial Orchestration
Authors: Bady Elena , Möller Katharina , Mandelkow Tim , Raedler Jonas B. , Yang Cheng , Ebner Julia , Lurati Magalie C.J. , Simon Ronald , Vettorazzi Eik , Büscheck Franziska , Luebke Andreas M. , Dum David , Menz Anne , Sauter Guido , Höflmayer Doris , Weidemann Sören , Fraune Christoph , Uhlig Ria , Bernreuther Christian , Jacobsen Frank , Clauditz Till S. , Wilczak Waldemar , Burandt Eike , Steurer Stefan , Minner Sarah , Lennartz Maximilian , Blessin Niclas C.
Published: June 2023

Figure S1a: Representative images of the BLEACH&STAIN 15+1 staining.Figure S1b: BLEACH&STAIN 15+1 validation.Figure S2: Deep learning framework for automated cell type identification.Figure S3: Performance of a Deep Learning-based framework for cell type identification compared to manual set thresholds.Figure S4: Comparison between BLEACH&STAIN and manual PD-L1 assessment.Figure S5: Immune phenotype identification.Figure S6: Association between the immune phenotypes and the individual immune cell parameters.Figure S7: Representative image of the 6 major immune phenotypes of Figure 2Figure S8a: Association between PD-L1 phenotypes and clinico-histopathological parameters.Figure S8b: Distribution of six PD-L1 phenotypes across 44 carcinoma entities.Figure S9: Spatial orchestration of immune cells across the PD-L1 immune phenotypes.Figure S10: Representative image of the spatial orchestration shown in Figure 3Figure S11: Composition of immune cells across the three PD-L1 phenotypesFigure S12: Prognosis analysis of spatial immune parameters in breast cancer for overall 5-years survival after surgery.Table S1: TMA cohort of the PD-L1 15+1 study.Table S2: List of the used antibodies, antigen retrieval (AR), dilutions, and Opal dyes for multiplex fluorescence immunohistochemistry.Table S3: List of 132 immune cell (sub)population.Table S4: Associations between spatial parameters and PD-L1 phenotypes were independent from the used threshold.Table S5: Immune landscape of 3098 human carcinoma samples.