bluuebunny/crossref_metadata_2025 huggingface dataset:
Supplementary Table S11 from Type 2 Diabetes Mellitus and Efficacy Outcomes from Immune 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

Summary of baseline characteristics of patients included in the targeted transcriptome analysis.
Supplementary Figure S12 from TIGIT Expression Delineates T-cell Populations with Distinct Functional and Prognostic Impact in Pancreatic Cancer
Authors: Heiduk Max , Klimova Anna , Reiche Charlotte , Digomann David , Beer Carolin , Aust Daniela E. , Distler Marius , Weitz Jürgen , Seifert Adrian M. , Seifert Lena
Published: June 2023

Survival analyses for PD-1 and TIGIT co-expression in PDAC.
Supplementary Figure S11 from TIGIT Expression Delineates T-cell Populations with Distinct Functional and Prognostic Impact in Pancreatic Cancer
Authors: Heiduk Max , Klimova Anna , Reiche Charlotte , Digomann David , Beer Carolin , Aust Daniela E. , Distler Marius , Weitz Jürgen , Seifert Adrian M. , Seifert Lena
Published: June 2023

Survival analyses for PD-1 and TIGIT co-expression in blood.
Supplementary Table S10 from Type 2 Diabetes Mellitus and Efficacy Outcomes from Immune 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

Detailed random blood sugar test results used to compute the median baseline glycaemia (MBG). 133 patients included (30 from the Pascale Cancer Institute and 103 from Imperial College London Cohort.
Supplementary Figure S10 from TIGIT Expression Delineates T-cell Populations with Distinct Functional and Prognostic Impact in Pancreatic Cancer
Authors: Heiduk Max , Klimova Anna , Reiche Charlotte , Digomann David , Beer Carolin , Aust Daniela E. , Distler Marius , Weitz Jürgen , Seifert Adrian M. , Seifert Lena
Published: June 2023

Kaplan-Meier analyses for PD-1 and TIGIT co-expression in blood.
Supplementary Methods S1 from Type 2 Diabetes Mellitus and Efficacy Outcomes from Immune 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

Tumour micron-environment transcriptome analysis.
Supplementary Table S2 from Additional Oncogenic Alterations in RAS-Driven Differentiated Thyroid Cancers Associate with Worse Clinicopathologic Outcomes
Authors: Bikas Athanasios , Ahmadi Sara , Pappa Theodora , Marqusee Ellen , Wong Kristine , Nehs Matthew A. , Cho Nancy L. , Haase Jacob , Doherty Gerard M. , Sehgal Kartik , Barletta Justine A. , Alexander Erik K. , Landa Iñigo
Published: June 2023

Supplementary Table S2. Characteristics of patients with RAS-mutant anaplastic thyroid cancer
Supplementary Figure S6 from Type 2 Diabetes Mellitus and Efficacy Outcomes from Immune 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

Scatter diagram with regression line summarizing the linear regression analysis between the median baseline glycaemia (used as independent variable: x-axes) and median baseline NLR (used as dependent variable: y-axes). 133 patients included; A significant regression equation was found F(1,131)= 4.09, p = 0.04) with an R2 of .030. NLR: neutrophil to lymphocyte ratio.
Supplementary Figure S5 from Type 2 Diabetes Mellitus and Efficacy Outcomes from Immune 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

Kaplan-Meier survival estimates according to the receipt of no diabetes medication, other diabetes medications/insulin therapy only, and metformin therapy (either alone or in combinations). A) Overall Survival whole cohort; patients not receiving diabetes medications: 18.9 months (95%CI: 15.9-21.6; 684 events), patients on other diabetes medications/insulin therapy only: 19.3 months (95%CI: 11.6-22.9; 48 events), patients on metformin: 12.3 months (95%CI: 9.8-15.9; 100 events). B) Progression Free Survival whole cohort; patients not receiving diabetes medications: 8.2 months (95%CI: 7.1-9.4; 872 events), patients on other diabetes medications/insulin therapy only: 10.7 months (95%CI: 6.7-11.6; 61 events), patients on metformin: 7.9 months (95%CI: 5.1-10.1; 124 events).
Supplementary Figure S4 from Type 2 Diabetes Mellitus and Efficacy Outcomes from Immune 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

Kaplan-Meier survival estimates according to the receipt of other diabetes medications and insulin therapy. A) Overall Survival whole cohort; patients on other oral antidiabetic drugs and insulin therapy: 17.5 months (95%CI: 12.8-20.9; 82 events), patients not receiving other oral diabetes medications and insulin therapy 17.8 months (95%CI: 15.4 – 19.7; 750 events). B) Progression Free Survival whole cohort; other oral diabetes medications and insulin therapy: 8.2 months (95%CI: 6.2-11.4; 106 events), patients not receiving other oral diabetes medications and insulin therapy: 8.1 months (95%CI: 7.1 – 9.2; 951 events).
Data from Preclinical Efficacy of the Antibody–Drug Conjugate CLDN6–23-ADC for the Treatment of CLDN6-Positive Solid Tumors
Authors: McDermott Martina S.J. , O'Brien Neil A. , Hoffstrom Benjamin , Gong KeWei , Lu Ming , Zhang Jun , Luo Tong , Liang Min , Jia Weiping , Hong Jenny J. , Chau Kevin , Davenport Simon , Xie Bin , Press Michael F. , Panayiotou Richard , Handly-Santana Abram , Brugge Joan S. , Presta Leonard , Glaspy John , Slamon Dennis J.
Published: June 2023

AbstractPurpose:
Claudin-6 (CLDN6) is expressed at elevated levels in multiple human cancers including ovarian and endometrial malignancies, with little or no detectable expression in normal adult tissue. This expression profile makes CLDN6 an ideal target for development of a potential therapeutic antibody–drug conjugate (ADC). This study describes the generation and preclinical characterization of CLDN6–23-ADC, an ADC consisting of a humanized anti-CLDN6 monoclonal antibody coupled to monomethyl auristatin E (MMAE) via a cleavable linker.
Experimental Design:
A fully humanized anti-CLDN6 antibody was conjugated to MMAE resulting in the potential therapeutic ADC, CLDN6–23-ADC. The antitumor efficacy of CLDN6–23-ADC was assessed for antitumor efficacy in CLDN6-positive (CLDN6+) and -negative (CLDN6−) xenografts and patient-derived xenograft (PDX) models of human cancers.
Results:
CLDN6–23-ADC selectively binds to CLDN6, versus other CLDN family members, inhibits the proliferation of CLDN6+ cancer cells in vitro, and is rapidly internalized in CLDN6+ cells. Robust tumor regressions were observed in multiple CLDN6+ xenograft models and tumor inhibition led to markedly enhanced survival of CLDN6+ PDX tumors following treatment with CLDN6–23-ADC. IHC assessment of cancer tissue microarrays demonstrate elevated levels of CLDN6 in 29% of ovarian epithelial carcinomas. Approximately 45% of high-grade serous ovarian carcinomas and 11% of endometrial carcinomas are positive for the target.
Conclusions:
We report the development of a novel ADC, CLDN6–23-ADC, that selectively targets CLDN6, a potential onco-fetal-antigen which is highly expressed in ovarian and endometrial cancers. CLDN6–23-ADC exhibits robust tumor regressions in mouse models of human ovarian and endometrial cancers and is currently undergoing phase I study.
Data from Multicenter Phase I Trial of Ivosidenib as Maintenance Treatment Following Allogeneic Hematopoietic Cell Transplantation for IDH1-Mutated Acute Myeloid Leukemia
Authors: Fathi Amir T. , Kim Haesook T. , Soiffer Robert J. , Levis Mark J. , Li Shuli , Kim Annette S. , DeFilipp Zachariah , El-Jawahri Areej , McAfee Steve L. , Brunner Andrew M. , Amrein Philip C. , Mims Alice S. , Knight Laura W. , Kelley Devon , Bottoms AJ S. , Perry Lindsey H. , Wahl Jonathan L. , Brock Jennifer , Breton Elayne , Marchione Dylan M. , Ho Vincent T. , Chen Yi-Bin
Published: June 2023

AbstractPurpose:
Isocitrate dehydrogenase 1 (IDH1) mutations occur in 5% to 10% of patients with acute myeloid leukemia (AML). Ivosidenib is an IDH1 inhibitor, approved for use in patients with IDH1-mutated AML.
Patients and Methods:
We conducted a multicenter, phase I trial of maintenance ivosidenib following allogeneic hematopoietic cell transplantation (HCT) in patients with IDH1-mutated AML. Ivosidenib was initiated between days 30 and 90 following HCT and continued for up to 12 28-day cycles. The first dose level was 500 mg daily, with level reduction to 250 mg daily, if needed, in a 3 × 3 de-escalation design. Ten additional patients would then receive the MTD or recommended phase 2 dose (RP2D). The primary endpoint was establishing the MTD or RP2D of ivosidenib.
Results:
Eighteen patients were enrolled, of whom 16 initiated post-HCT ivosidenib. One dose-limiting toxicity, grade(g) 3 QTc prolongation, was observed. The RP2D was established at 500 mg daily. Attributable g≥3 adverse events were uncommon, with the most common being QTc prolongation in 2 patients. Eight patients discontinued maintenance, with only one due to adverse event. Six-month cumulative incidence (CI) of gII-IV aGVHD was 6.3%, and 2-year CI of all cGVHD was 63%. Two-year CI of relapse and nonrelapse mortality (NRM) were 19% and 0%, respectively. Two-year progression-free (PFS) was 81%, and 2-year overall survival (OS) was 88%.
Conclusions:
Ivosidenib is safe and well-tolerated as maintenance therapy following HCT. Cumulative incidence of relapse and NRM, as well as estimations of PFS and OS, were promising in this phase I study.
Data from [18F]FDG and [18F]FES PET/CT Imaging as a Biomarker for Therapy Effect in Patients with Metastatic ER+ Breast Cancer Undergoing Treatment with Rintodestrant
Authors: Iqbal Ramsha , Yaqub Maqsood , Bektas Huseyyin O. , Oprea-Lager Daniela E. , de Vries Elisabeth G.E. , Glaudemans Andor W.J.M. , Aftimos Philippe , Gebhart Géraldine , Beelen Andrew P. , Schuit Robert C. , Windhorst Albert D. , Boellaard Ronald , Menke-van der Houven van Oordt C. Willemien
Published: June 2023

AbstractPurpose:
PET with 16α-[18F]-fluoro-17β-estradiol ([18F]FES) allows assessment of whole body estrogen receptor (ER) expression. The aim of this study was to investigate [18F]-fluorodeoxyglucose ([18F]FDG) and [18F]FES PET/CT imaging for response prediction and monitoring of drug activity in patients with metastatic ER-positive breast cancer undergoing treatment with the selective estrogen receptor downregulator (SERD) rintodestrant.
Experimental Design:
In this trial (NCT03455270), PET/CT imaging was performed at baseline ([18F]FDG and [18F]FES), during treatment and at time of progression (only [18F]FES). Visual, quantitative, and mutational analysis was performed to derive a heterogeneity score (HS) and assess tracer uptake in lesions, in relation to the mutation profile. The primary outcome was progression-free survival (PFS).
Results:
The HS and PFS in the entire group did not correlate (n = 16, Spearman's rho, P = 0.06), but patients with a low HS (< 25.0%, n = 4) had a PFS of > 5 months whereas patients with no [18F]FES uptake (HS 100.0%, n = 3) had a PFS of < 2 months. [18F]FES uptake was not affected by estrogen receptor 1 (ESR1) mutations. On-treatment [18F]FES PET/CT scans showed no [18F]FES uptake in any of the baseline [18F]FES-positive lesions. At progression, [18F]FES uptake remained blocked in patients scanned ≤ 1–2 half-lives of rintodestrant whereas it restored in patients scanned ≥ 5 days after end of treatment.
Conclusions:
Absence of ER expression on [18F]FES PET is a predictor for no response to rintodestrant. [18F]FES uptake during treatment and at time of progression is useful to monitor the (reversible) effect of therapy and continued mode of action of SERDs.

See related commentary by Linden and Mankoff, p. 2015
Data from Alternating 17beta-estradiol and aromatase inhibitor therapies is efficacious in post-menopausal women with advanced endocrine-resistant ER+ breast cancer
Authors: Schwartz Gary N. , Kaufman Peter A. , Giridhar Karthik V. , Marotti Jonathan D. , Chamberlin Mary D. , Arrick Bradley A. , Makari-Judson Grace , Goetz Matthew P. , Soucy Shannon M. , Kolling Fred , Demidenko Eugene , Miller Todd W.
Published: June 2023

Abstract
Purpose: Strategies to implement estrogen therapy for advanced estrogen receptor (ER)-positive breast cancer are under-developed. Preclinical data suggest that cycling treatment with 17b-estradiol followed by estrogen deprivation can control tumor growth long-term. Experimental Design: Post-menopausal women with advanced ER+/HER2- breast cancer with recurrence or progression on ≥1 anti-estrogen- or aromatase inhibitor (AI)-based therapy were eligible. Patients received 17b-estradiol (2 mg orally TID) for 8 weeks followed by AI (physician’s choice) for 16 weeks, alternating treatments on an 8-week/16-week schedule until disease progression. Patients then optionally received continuous single-agent treatment until a second instance of disease progression. Endpoints included 24-week clinical benefit and objective response per RECIST, and tumor genetic alterations. Results: Of 19 evaluable patients, clinical benefit rate was 42.1% (95% CI: 23.1-63.9%) and objective response rate was 15.8% (95% CI: 5.7-37.9%). One subject experienced a grade 3 adverse event related to 17b-estradiol. Among patients who received continuous single-agent treatment until a second instance of disease progression, clinical benefit was observed in 5/12 (41.7%) cases. Tumor ER (ESR1) mutations were found by whole-exome profiling in 4/7 (57.1%) vs. 2/9 (22.2%) patients who did vs. did not experience clinical benefit from alternating 17b-estradiol/AI therapy. The only two patients to experience objective responses to initial 17b-estradiol had tumor ESR1 mutations. Conclusions: Alternating 17b-estradiol/aromatase inhibitor therapy may be a promising treatment for endocrine-refractory ER+ breast cancer, including following progression on CDK4/6 inhibitors or everolimus. Further study is warranted to determine whether the anti-tumor activity of 17b-estradiol differs according to ESR1 mutation status.
Data from Alternating 17β-Estradiol and Aromatase Inhibitor Therapies Is Efficacious in Postmenopausal Women with Advanced Endocrine-Resistant ER+ Breast Cancer
Authors: Schwartz Gary N. , Kaufman Peter A. , Giridhar Karthik V. , Marotti Jonathan D. , Chamberlin Mary D. , Arrick Bradley A. , Makari-Judson Grace , Goetz Matthew P. , Soucy Shannon M. , Kolling Fred , Demidenko Eugene , Miller Todd W.
Published: June 2023

AbstractPurpose:
Strategies to implement estrogen therapy for advanced estrogen receptor–positive (ER+) breast cancer are underdeveloped. Preclinical data suggest that cycling treatment with 17β-estradiol followed by estrogen deprivation can control tumor growth long-term.
Patients and Methods:
Postmenopausal women with advanced ER+/HER2− breast cancer with recurrence or progression on ≥ 1 antiestrogen or aromatase inhibitor (AI)-based therapy were eligible. Patients received 17β-estradiol (2 mg orally, three times a day) for 8 weeks followed by AI (physician's choice) for 16 weeks, alternating treatments on an 8-week/16-week schedule until disease progression. Patients then optionally received continuous single-agent treatment until a second instance of disease progression. Endpoints included 24-week clinical benefit and objective response per RECIST, and tumor genetic alterations.
Results:
Of 19 evaluable patients, clinical benefit rate was 42.1% [95% confidence interval (CI), 23.1%–63.9%] and objective response rate (ORR) was 15.8% (95% CI, 5.7%–37.9%). One patient experienced a grade 3 adverse event related to 17β-estradiol. Among patients who received continuous single-agent treatment until a second instance of disease progression, clinical benefit was observed in 5 of 12 (41.7%) cases. Tumor ER (ESR1) mutations were found by whole-exome profiling in 4 of 7 (57.1%) versus 2 of 9 (22.2%) patients who did versus did not experience clinical benefit from alternating 17β-estradiol/AI therapy. The only two patients to experience objective responses to initial 17β-estradiol had tumor ESR1 mutations.
Conclusions:
Alternating 17β-estradiol/AI therapy may be a promising treatment for endocrine-refractory ER+ breast cancer, including following progression on CDK4/6 inhibitors or everolimus. Further study is warranted to determine whether the antitumor activity of 17β-estradiol differs according to ESR1 mutation status.
Data from TIGIT expression delineates T cell populations with distinct functional and prognostic impact in pancreatic cancer
Authors: Heiduk Max , Klimova Anna , Reiche Charlotte , Digomann David , Beer Carolin , Aust Daniela E. , Distler Marius , Weitz Jürgen , Seifert Adrian M. , Seifert Lena
Published: June 2023

Abstract
Purpose: Immunotherapy has led to a fundamental shift in the treatment of several cancers. However, its efficacy in pancreatic ductal adenocarcinoma (PDAC) is limited. Understanding the expression of inhibitory immune checkpoint receptors (ICR) by intratumoral T cells may help to unravel their involvement in insufficient T cell-mediated antitumor immunity. Experimental Design: Using multicolor flow cytometry, we analyzed circulating and intratumoral T cells from blood (n = 144) and matched tumor samples (n = 107) of PDAC patients. We determined the expression of PD-1 and TIGIT by CD8+ T cells, conventional CD4+ T cells (Tconv) and regulatory T cells (Treg) and their association with T cell differentiation, tumor reactivity, and cytokine expression. A comprehensive follow-up was used to determine their prognostic value. Results: Intratumoral T cells were characterized by increased PD-1 and TIGIT expression. Both markers delineated distinct T cell subpopulations. PD-1+TIGIT- T cells highly expressed proinflammatory cytokines and markers of tumor reactivity (CD39, CD103), whereas TIGIT expression was linked to antiinflammatory and exhausted phenotypes. In addition, the enhanced presence of intratumoral PD-1+TIGIT- Tconv was associated with improved clinical outcomes, while high ICR expression on blood T cells was a significant hazard for overall survival. Conclusions: Our results uncover the association between ICR expression and T cell functionality. PD-1 and TIGIT characterized intratumoral T cells with highly divergent phenotypes linked to clinical outcomes, further underscoring the relvance of TIGT for immunotherapeutic approaches in PDAC. The prognostic value of ICR expression in patient blood may be a valuable tool for patient stratification.
Supplementary Table 2 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

List of oligonucleotides
Supplementary Figure 5 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

Pharmacological inhibition of BET family members by JQ-1.
Supplementary Figure 4 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

Loss of Rb results in altered gene expression that promotes immune suppression as well as increased Tmem173/STING expression.
Supplementary Figures 1-5 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

Supplementary Figures 1-5
Supplementary Data from Preclinical Profile of BYON3521 Predicts an Effective and Safe MET Antibody–Drug Conjugate
Authors: Groothuis Patrick G. , Jacobs Daniëlle C.H. , Hermens Inge A.T. , Damming Désirée , Berentsen Kim , Mattaar-Hepp Ellen , Stokman Marloes E.M. , Boekel Tinie van , Rouwette Myrthe , van der Vleuten Monique A.J. , Sesink Aloys , Dijcks Fred A. , Coumans Ruud G.E. , Schouten Jan , Glaudemans Dirk H. , Wijk Daniëlle van , Blomenröhr Marion , Kappers Wendela A. , Ubink Ruud , van der Lee Miranda M.C. , Dokter Wim H.A.
Published: June 2023

Supplementary tables and figures
Supplementary Online Material from 3D-Informed Targeting of the Trop-2 Signal-Activation Site Drives Selective Cancer Vulnerability
Authors: Guerra Emanuela , Trerotola Marco , Relli Valeria , Lattanzio Rossano , Tripaldi Romina , Ceci Martina , Boujnah Khouloud , Pantalone Ludovica , Sacchetti Andrea , Havas Kristina M. , Simeone Pasquale , Travali Nicole , Querzoli Patrizia , Pedriali Massimo , Roversi Pietro , Iezzi Manuela , Tinari Nicola , Antolini Laura , Alberti Saverio
Published: June 2023

Supplementary Online Material
Table 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

Genes regulated by GT103 in CR2+ intratumoral B cells
Figure S5 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 phosphorylated Syk kinase in B cells.
Supplementary Table1 from Activating an Adaptive Immune Response with a Telomerase-Mediated Telomere Targeting Therapeutic in Hepatocellular Carcinoma
Authors: Mender Ilgen , Siteni Silvia , Barron Summer , Flusche Ann Marie , Kubota Naoto , Yu Chunhua , Cornelius Crystal , Tedone Enzo , Maziveyi Mazvita , Grichuk Anthony , Venkateswaran Niranjan , Conacci-Sorrell Maralice , Hoshida Yujin , Kang Rui , Tang Daolin , Gryaznov Sergei , Shay Jerry W.
Published: June 2023

Supplementary Table1
Data from Targeting RET Solvent-Front Mutants with Alkynyl Nicotinamide-Based Inhibitors
Authors: Khatri Ujjwol , Dayal Neetu , Hu Xueqing , Larocque Elizabeth , Naganna Nimishetti , Shen Tao , Liu Xuan , Holtsberg Frederick W. , Aman M. Javad , Sintim Herman O. , Wu Jie
Published: June 2023

Abstract
Selpercatinib (LOXO292) and pralsetinib (BLU667) are RET protein tyrosine kinase inhibitors (TKIs) recently approved for treating RET-altered cancers. However, RET mutations that confer selpercatinib/pralsetinib resistance have been identified, necessitating development of next-generation RET TKIs. While acquired RET G810C/R/S/V mutations were reported in selpercatinib-treated patients, it was unclear whether all of these and other potential G810 mutants are resistant to selpercatinib and pralsetinib. Here, we profiled selpercatinib and pralsetinib on all six possible G810 mutants derived from single nucleotide substitution and developed novel alkynyl nicotinamide-based RET TKIs to inhibit selpercatinib/pralsetinib-resistant RET G810 mutants. Surprisingly, the G810V mutant found in a clinical study was not resistant to selpercatinib or pralsetinib. Besides G810C/R/S, G810D also conferred selpercatinib/pralsetinib resistance. Alkynyl nicotinamide compounds such as HSN608, HSL476, and HSL468 have better drug-like properties than alkynyl benzamides. Six of these compounds inhibited all six G810 solvent-front mutants and the V804M gatekeeper mutant with IC50 < 50 nmol/L in cell culture. Oral administration of HSN608 at a well-tolerated dose (30 mg/kg) gave plasma level > 30x the IC50s of inhibiting all G810 mutants in cell culture. In cell-derived xenograft tumors driven by KIF5B-RET (G810C) that contains the most frequently observed solvent-front mutant in selpercatinib-treated patients, HSN608, HSL476, and HSL468 significantly suppressed and caused regression of the selpercatinib-resistant tumors. This study clarifies the sensitivities of different RET solvent-front mutants to selpercatinib and pralsetinib and identifies novel alkylnyl nicotinamide-based RET TKIs for inhibiting selpercatinib/pralsetinib-resistant G810 mutants.
Data from Targeting Glutamine Metabolism with a Novel Na+/K+-ATPase Inhibitor RX108 in Hepatocellular Carcinoma
Authors: Wei Daoyan , Chen Dongmei , Mou Hongyuan , Chakraborty Sharmistha , Wei Bo , Tan Lin , Lorenzi Philip L. , Qian Xiangping , Yang Peiying
Published: June 2023

Abstract
The poor prognosis and limited therapeutic options for human hepatocellular carcinoma (HCC), the most common form of liver cancer, highlight the urgent need to identify novel therapeutic modalities. Here, we describe the antitumor activity and underlying molecular mechanisms of a novel Na+/K+-ATPase inhibitor RX108 in human HCC cells and its xenograft model. RX108 dose-dependently inhibited HCC cell proliferation in vitro and tumor growth in a xenograft mouse model, and that the inhibition was associated with induction of apoptosis. Mechanistically, RX108 significantly downregulated alanine serine cysteine transporter 2 (ASCT2) protein expression and reduced glutamine and glutamate concentration in HCC cells and tumors. In addition, RX108 exposure led to a significant decrease in cell energy metabolism in Huh7 and Hep3B cells, including decreased levels of glutathione, NADH, NADPH, and mitochondrial respiration oxygen consumption rate. Furthermore, HCC cells exhibited evidence of glutamine addiction; the antiproliferative effect of RX108 was dependent on glutamine transport. Clinically, elevated ASCT2 mRNA expression in HCCs was associated with unfavorable survival. Taken together, these findings reveal a novel approach to target glutamine metabolism through inhibiting Na+/K+-ATPase and provide a rationale for using RX108 to treat HCC in patients whose tumors express ASCT2 at high levels. RX108 is currently under clinical development.
Abstract 21: Clinical Trials in Gastroesophageal Cancers: An Analysis of the Global Landscape of Interventional Trials From ClinicalTrials.gov
Authors: Falade Ayo , Adeoye Oluwatayo , Buckle Geoffrey
Published: June 2023

Purpose: This study aims to describe the global landscape of clinical research into interventions for gastroesophageal (GE) cancers, which are a leading cause of cancer morbidity and mortality worldwide. We examine trial characteristics, focusing on geographic distribution of trial sites, participation of low-and-middle-income countries (LMICs), and factors associated with premature trial termination.

Methods: We queried ClinicalTrials.gov database to identify all completed or terminated Phase III interventional studies investigating GE cancers (esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC), gastroesophageal junctional (GEJ) and gastric adenocarcinoma). All reported characteristics were extracted. Pearson’s chi-square and Fisher’s exact test were used to compare differences in completed and terminated trials. Multivariate logistic regression was used to determine predictors of termination.

Results: A total of 179 trials were identified; 90% were therapeutic. Most included sites in Asia (61%), Europe (32%), and North America (23%); few included sites in South America (9%), Africa (4%), and Oceania (9%). 63% of trials included high-income countries (HICs) sites alone; only 7% included sites in lower-middle or low-income countries. Most (70%) focused exclusively on gastric or GEJ adenocarcinoma, 13% on EAC and ESCC, and 9% ESCC alone. 16% (n=29) of trials terminated, most due to accrual difficulties (n=13, 44%). In multivariate analysis, study site number, location, and eligible patient population emerged as predictors of termination. Trials conducted exclusively in the US were more likely to terminate (OR 7.22 [95% CI 1.59-32.69]). Conversely, trials conducted exclusively in LMICs were less likely to terminate (OR 0.04 [95% CI 0.01-0.59] v conducted in HIC alone). Studies on ESCC were more likely to terminate (OR 17.74 [95%CI 1.49-210.69]). Trial design characteristics, intervention characteristics, and funding sources were not associated with termination.

Conclusion: Although 80% of GE malignancies occur in LMICs, trial activity disproportionately occurs in HICs. Few trials focus on EAC/ESCC despite being highly fatal, highlighting an unmet need. Geographic location of trial sites emerged as a predictor of trial termination, with studies involving LMICs sites less likely to terminate prematurely. This finding highlights the potential benefit of including LMICs in future clinical trials to advance research for these diseases.

Citation Format: Ayo Falade, Oluwatayo Adeoye, Geoffrey Buckle. Clinical Trials in Gastroesophageal Cancers: An Analysis of the Global Landscape of Interventional Trials From ClinicalTrials.gov [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 21.
Abstract 30: Development of a Breast Cancer Survivorship Health System Needs Assessment Questionnaire (BSH-Q) for Malaysian Health Institutions
Authors: Islam Tania , Azmi Syahidatul Akmal , Jamarish Suniza , Shaharuddin Fatiha Hana , Engkasan Julia Patrick , Taib Nur Aishah
Published: June 2023

Purpose: There is a need to develop and implement a Breast Cancer Survivorship Care Plan in Malaysia based on the available healthcare resources and services. The objective of the study is to develop a Breast Cancer Survivorship Health System Needs Assessment Questionnaire (BSH-Q) using the Delphi method.

Methods: The three rounds of e-Delphi surveys were conducted from November, 2020 to April, 2021. Development of BSH-Q was accomplished amongst key stakeholders (multidisciplinary healthcare professionals involved in cancer care in public hospitals, NGOs and breast cancer survivors). The first Delphi round was intended to explore the barriers, facilitators and needs of healthcare providers focused on five main survivorship care domains. The questions were open ended, allowing expert participants to brainstorm their ideas. Delphi round two involved a ranking exercise of the newly developed questionnaire based on the first Delphi round. A five point Likert scale was used to rate the importance of each item. This was followed with a pilot study to determine the feasibility of the research process, and face validity of the questionnaire. The pilot study was tested on healthcare providers working in University Malaya Medical Centre representing the five respective domains: Rehabilitation, life-style, psychosocial, financial, and genetic counselling. The participants were selected based on their involvement in managing the healthcare issues related to the five domains.

Results: A total of 55 participants responded to the Delphi survey. Following the first Delphi survey, a total of 95 questions were developed in the domains of psychosocial, lifestyle, financial, rehabilitation, genetic counselling, cancer surveillance and management. In the second Delphi survey, 39 participants responded, they selected a total of 196 questions as important and finally 182 relevant questions were developed for the final BSH-Q version. The newly developed BSH-Q underwent a pilot study with no major modifications to the questionnaire.

Conclusion: The Delphi survey method is suitable to develop the BSH-Q questionnaire. The newly developed BSH-Q is a valuable tool for Malaysia to analyse existing services in the country to provide a needs assessment too for the development of an implementation framework cancer survivorship care in Malaysia.

Citation Format: Tania Islam, Syahidatul Akmal Azmi, Suniza Jamarish, Fatiha Hana Shaharuddin, Julia Patrick Engkasan, Nur Aishah Taib. Development of a Breast Cancer Survivorship Health System Needs Assessment Questionnaire (BSH-Q) for Malaysian Health Institutions [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 30.
Abstract 42: Hematopoietic Stem Cell Transplants and Treatment of Severe Blood Disorders: Role of Providers in Medical Tourism
Authors: Khanna Deepika , Rondelli Damiano
Published: June 2023

Purpose: Medical tourism provides international patients with medical services, but little data is present on the role of medical tourism in regard to hematopoietic stem cell transplant (HSCT) services. Over the last 10 years, the University of Illinois at Chicago Blood & Marrow Transplant program has established an international network (GlobalBMT) of LMIC centers, that includes hospitals in Nepal, India, Nigeria, Tanzania, Bolivia, Cuba, Argentina, Ukraine. This project involves each hospital of the GlobalBMT network to: 1. qualitatively assess the current role of medical providers in international care of HSCT patients and 2. quantitatively and qualitatively assess the current policies of medical institutions for sending and accepting international transplant candidates.

Methods: This is a mixed-methods cross-sectional study with a quantitative component (questionnaire) and a qualitative component (interview). A questionnaire was disseminated to 12 medical providers in 8 countries, who either refer or accept international HSCT patients, to assess the demographics, volume, and frequency of international referrals. We also conducted semi-structured virtual interviews with willing healthcare providers to qualitatively assess the current infrastructure in medical tourism for international HSCT candidates, as well as elicit ways in which this structure can be improved.

Results: Here we will report on the results of the mixed-methods cross-sectional study that was conducted within the GlobalBMT network. In the setting of this research project, we suggest a need for a formalized provider-to-provider framework in the sphere of medical tourism for HSCT patients to be sent outside of their home countries to receive a HSCT, diminishing the impact of third party brokers and misinformation. Our data have uncovered themes in the existing structure of third-party agents searching for a profit, difficulty connecting with home physicians to coordinate care, and limited information for patients on the procedure.

Conclusion: The data collected in this project provide an example of existing structures in medical tourism for HSCT in some LMICs. Gaps in center-to-center patient information, role of middle-men directly contacting patient families, or lack of advanced medical care in LMIC, are some of the relevant findings that based on this initial study could be exploited in a large multicenter international registry study.

Citation Format: Deepika Khanna, Damiano Rondelli. Hematopoietic Stem Cell Transplants and Treatment of Severe Blood Disorders: Role of Providers in Medical Tourism [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 42.
Abstract 48: Identifying Temporal Patterns in Healthcare Service-Use Trajectories of Long-Term Breast Cancer Survivors
Authors: Giannoula Alexia , Comas Mercè , Gonzalez José Martín Solorzano , Sanz Ferrán , Castells Xavier , Sala Maria
Published: June 2023

Purpose: Advances in the population screening programs and treatment efficacy, as well as, the rapidly aging global population, have led to a gradual increase of the number of long-term breast cancer survivors (BCS) in the past years. With the estimation for their survival rate to continue rising, it has become evident by the clinical and scientific community that BCS should be efficiently monitored in order to obtain a better understanding of their needs and subsequently, improve their medical care, further increase their survivorship and optimize the associated healthcare costs.

Methods: A novel data-mining methodology is proposed for the temporal analysis of healthcare service-use trajectories of long-term BCS. Specifically, an unsupervised clustering technique, based on Dynamic Time Warping, is applied on the extracted trajectories of a large longitudinal cohort (SURBCAN) of BCS and non-breast cancer (BC) women, with data on their contacts to all healthcare services. Introducing the time dimension permits the identification of complex time-dependent patterns (clusters) of the services that these women have used throughout the course of a five-year monitoring period. A comparison of the identified time patterns and the respective patient characteristics is also performed between the BCS (case) and non-BC (control) group.

Results: More than two hundred clusters representing temporal patterns of healthcare service use, were extracted for both the case and control group. It was found that the BCS group made a more complex and intense use of certain healthcare services, such as, radiology, outpatient care and hospital admission, than the control group. Furthermore, the corresponding mortality rates were significantly higher and a larger number of comorbidities (varying between different clusters) were registered at the beginning of the monitoring period in BCS. Additional patient characteristics and time information for certain paths of the extracted service-use network were reported and analyzed.

Conclusion: A flexible data-mining methodology was applied on a longitudinal cohort of long-term BCS for the identification of temporal patterns of healthcare service use, in an attempt to gain more insight into their needs, better predict their evolution, and subsequently, improve their received attention and eventually optimize the associated healthcare costs.

Citation Format: Alexia Giannoula, Mercè Comas, José Martín Solorzano Gonzalez, Ferrán Sanz, Xavier Castells, Maria Sala. Identifying Temporal Patterns in Healthcare Service-Use Trajectories of Long-Term Breast Cancer Survivors [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 48.
Abstract 49: Impact of Multimorbidity on Adherence to Follow-Up Recommendations for Long-Term Breast Cancer Survivors
Authors: Domingo Laia , Abbad David , Comas Mercè , Santiá Paula , Jansana Anna , Castells Xavier , Sala Maria
Published: June 2023

Purpose: To study the impact of comorbidities, multimorbidity, second primary cancers and socioeconomic determinants on adherence to follow-up recommendations for long-term breast cancer survivors (LTBCS), defined as women who survive 5 years or more after a primary breast cancer.

Methods: We identified women diagnosed with breast cancer between 2000-2006 and followed-up between 2012-2016, including those with at least one contact with health services (n=2,078). Follow-up recommendations for LTBCS in Spain include 1 annual visit plus 1 image test. A woman was considered adherent with >50% of years with annual image test and visit throughout follow-up period. Multivariate logistic regression models were adjusted to determine the relationship between adherence and comorbidities and multimorbidity (2 or more chronic diseases) and other clinical and sociodemographic variables. A hierarchical cluster analysis was used to define specific multimorbidity clusters. A sensitivity analysis was conducted with mammogram as specific image test. Statistical significance was considered at 5% level.

Results: Adherence to recommendations was 79.5% and 63.3% when considering mammograms only. We observed a higher adherence among LTBCS with multimorbidity, in those <70 years old, and with 5 to 9 years of survivorship. In the multivariate models, age under 40 years (OR=4.2; 95%CI: 2.3-7.6), a survivorship time between 5-9 years (OR=1.4; 95%CI: 1.1-1.8) and the metabolic and degenerative (OR=2.2 CI95%: 1.4-3.5) and thyroid disorders clusters (OR=2 IC95% 1.1-3.6) were associated with adherence. Similar results were observed in adjusted analyses by mammogram. In both analyses all multimorbidity clusters presented more adherence than LTBCS without chronic comorbidities. LTBCS with higher deprivation were found more adherent than LTBCS less deprived. Our results suggest a higher adherence among women experiencing second primary cancers, but the results were not statistically significant (OR=1.22; 95%CI: 0.8-2.0).

Conclusion: There are differences in adherence according to age, survivorship time, and presence of multimorbidity. These results suggest a moderate adherence to the current follow-up recommendations for certain groups, making it necessary to adapt clinical practice guidelines considering the comorbidities and characteristics of the patients.

Citation Format: Laia Domingo, David Abbad, Mercè Comas, Paula Santiá, Anna Jansana, Xavier Castells, Maria Sala. Impact of Multimorbidity on Adherence to Follow-Up Recommendations for Long-Term Breast Cancer Survivors [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 49.