bluuebunny/crossref_metadata_2025 huggingface dataset:
Supplementary Figure S10 from Durvalumab ± Tremelimumab + Platinum-Etoposide in Extensive-Stage Small Cell Lung Cancer (CASPIAN): Outcomes by PD-L1 Expression and Tissue Tumor Mutational Burden
Authors: Paz-Ares Luis , Garassino Marina Chiara , Chen Yuanbin , Reinmuth Niels , Hotta Katsuyuki , Poltoratskiy Artem , Trukhin Dmytro , Hochmair Maximilian J. , Özgüroğlu Mustafa , Ji Jun Ho , Statsenko Galina , Conev Nikolay , Bondarenko Igor , Havel Libor , Losonczy György , Xie Mingchao , Lai Zhongwu , Godin-Heymann Nadia , Mann Helen , Jiang Haiyi , Shrestha Yashaswi , Goldman Jonathan W.
Published: February 2024

Kaplan-Meier analysis of OS for (A) the tTMB <10 mut/Mb subgroup and (B) the tTMB ≥10 mut/Mb subgroup.
Supplemental Table 2 from Intrinsic Subtype and Overall Survival of Patients with Advanced HR+/HER2− Breast Cancer Treated with Ribociclib and ET: Correlative Analysis of MONALEESA-2, -3, -7
Authors: Prat Aleix , Solovieff Nadia , André Fabrice , O'Shaughnessy Joyce , Cameron David A. , Janni Wolfgang , Sonke Gabe S. , Yap Yoon-Sim , Yardley Denise A. , Partridge Ann H. , Thuerigen Astrid , Zarate Juan Pablo , Lteif Agnes , Su Fei , Carey Lisa A.
Published: February 2024

Supplemental Table 2. Patient characteristics by subtype
Supplemental Table 1 from Intrinsic Subtype and Overall Survival of Patients with Advanced HR+/HER2− Breast Cancer Treated with Ribociclib and ET: Correlative Analysis of MONALEESA-2, -3, -7
Authors: Prat Aleix , Solovieff Nadia , André Fabrice , O'Shaughnessy Joyce , Cameron David A. , Janni Wolfgang , Sonke Gabe S. , Yap Yoon-Sim , Yardley Denise A. , Partridge Ann H. , Thuerigen Astrid , Zarate Juan Pablo , Lteif Agnes , Su Fei , Carey Lisa A.
Published: February 2024

Supplemental Table 1. Representativeness of study participants
Supplemental Figure 1 from Intrinsic Subtype and Overall Survival of Patients with Advanced HR+/HER2− Breast Cancer Treated with Ribociclib and ET: Correlative Analysis of MONALEESA-2, -3, -7
Authors: Prat Aleix , Solovieff Nadia , André Fabrice , O'Shaughnessy Joyce , Cameron David A. , Janni Wolfgang , Sonke Gabe S. , Yap Yoon-Sim , Yardley Denise A. , Partridge Ann H. , Thuerigen Astrid , Zarate Juan Pablo , Lteif Agnes , Su Fei , Carey Lisa A.
Published: February 2024

Supplemental Figure 1: CONSORT diagrams of the MONALEESA (ML) trials.
Supplementary Table S6 from A Phase Ib Study of the DNA-PK Inhibitor Peposertib Combined with Neoadjuvant Chemoradiation in Patients with Locally Advanced Rectal Cancer
Authors: Romesser Paul B. , Capdevila Jaume , Garcia-Carbonero Rocio , Philip Tony , Fernandez Martos Carlos , Tuli Richard , Rodriguez-Gutierrez Almudena , Kuipers Mirjam , Becker Andreas , Coenen-Stass Anna , Sarholz Barbara , You Xiaoli , Miller Eric D.
Published: February 2024

Frequency of pathogenic/likely pathogenic loss-of-function mutation(s) in TP53, ATM and other CRC relevant genes and MSS/MSI status
Supplementary Table S5 from A Phase Ib Study of the DNA-PK Inhibitor Peposertib Combined with Neoadjuvant Chemoradiation in Patients with Locally Advanced Rectal Cancer
Authors: Romesser Paul B. , Capdevila Jaume , Garcia-Carbonero Rocio , Philip Tony , Fernandez Martos Carlos , Tuli Richard , Rodriguez-Gutierrez Almudena , Kuipers Mirjam , Becker Andreas , Coenen-Stass Anna , Sarholz Barbara , You Xiaoli , Miller Eric D.
Published: February 2024

PK parameters after single- and multiple-dose
Supplementary Table S3 from A Phase Ib Study of the DNA-PK Inhibitor Peposertib Combined with Neoadjuvant Chemoradiation in Patients with Locally Advanced Rectal Cancer
Authors: Romesser Paul B. , Capdevila Jaume , Garcia-Carbonero Rocio , Philip Tony , Fernandez Martos Carlos , Tuli Richard , Rodriguez-Gutierrez Almudena , Kuipers Mirjam , Becker Andreas , Coenen-Stass Anna , Sarholz Barbara , You Xiaoli , Miller Eric D.
Published: February 2024

Late toxicities by worst Grade (≥3) and System Organ Class
Supplementary Table S2 from A Phase Ib Study of the DNA-PK Inhibitor Peposertib Combined with Neoadjuvant Chemoradiation in Patients with Locally Advanced Rectal Cancer
Authors: Romesser Paul B. , Capdevila Jaume , Garcia-Carbonero Rocio , Philip Tony , Fernandez Martos Carlos , Tuli Richard , Rodriguez-Gutierrez Almudena , Kuipers Mirjam , Becker Andreas , Coenen-Stass Anna , Sarholz Barbara , You Xiaoli , Miller Eric D.
Published: February 2024

(A) Treatment-emergent adverse events (TEAEs) and (B) peposertib-related adverse events by system organ class and preferred term reported for ≥20% of patients overall at the preferred term level – safety analysis set.
Supplementary Table S5 from A Dysfunctional T-cell Gene Signature for Predicting Nonresponse to PD-1 Blockade in Non–small Cell Lung Cancer That Is Suitable for Routine Clinical Diagnostics
Authors: Hummelink Karlijn , Tissier Renaud , Bosch Linda J.W. , Krijgsman Oscar , van den Heuvel Michel M. , Theelen Willemijn S.M.E. , Damotte Diane , Goldwasser François , Leroy Karen , Smit Egbert F. , Meijer Gerrit A. , Thommen Daniela S. , Monkhorst Kim
Published: February 2024

Predictive accuracy of PDCD1 gene expression signature, summary of training and validation results.
Supplementary Table S4 from A Dysfunctional T-cell Gene Signature for Predicting Nonresponse to PD-1 Blockade in Non–small Cell Lung Cancer That Is Suitable for Routine Clinical Diagnostics
Authors: Hummelink Karlijn , Tissier Renaud , Bosch Linda J.W. , Krijgsman Oscar , van den Heuvel Michel M. , Theelen Willemijn S.M.E. , Damotte Diane , Goldwasser François , Leroy Karen , Smit Egbert F. , Meijer Gerrit A. , Thommen Daniela S. , Monkhorst Kim
Published: February 2024

Overview of significantly expressed genes between tumors from PD-1T IHC high patients (n=12) and PD-1T IHC low patients (n=29).
Supplementary Figure S6 from A Composite Decision Rule of CD8+ T-cell Density in Tumor Biopsies Predicts Efficacy in Early-stage, Immunotherapy Trials
Authors: Dejardin David , Kraxner Anton , Blank Annika , Rieder Natascha , Teichgräber Volker , Städler Nicolas , Beyer Ulrich , Gomes Bruno , Charo Jehad
Published: February 2024

Baseline density distribution in the cohorts reported with decision rule.
Supplementary Figure S5 from A Composite Decision Rule of CD8+ T-cell Density in Tumor Biopsies Predicts Efficacy in Early-stage, Immunotherapy Trials
Authors: Dejardin David , Kraxner Anton , Blank Annika , Rieder Natascha , Teichgräber Volker , Städler Nicolas , Beyer Ulrich , Gomes Bruno , Charo Jehad
Published: February 2024

Higher response rate in groups above CD8 density threshold.
Supplementary Figure S4 from A Composite Decision Rule of CD8+ T-cell Density in Tumor Biopsies Predicts Efficacy in Early-stage, Immunotherapy Trials
Authors: Dejardin David , Kraxner Anton , Blank Annika , Rieder Natascha , Teichgräber Volker , Städler Nicolas , Beyer Ulrich , Gomes Bruno , Charo Jehad
Published: February 2024

Derivation of CD8 density FC and OTD thresholds.
Supplementary Figure S2 from A Composite Decision Rule of CD8+ T-cell Density in Tumor Biopsies Predicts Efficacy in Early-stage, Immunotherapy Trials
Authors: Dejardin David , Kraxner Anton , Blank Annika , Rieder Natascha , Teichgräber Volker , Städler Nicolas , Beyer Ulrich , Gomes Bruno , Charo Jehad
Published: February 2024

Association between immune cell subsets and PFS.
Table S3 from Osteosarcoma PDX-Derived Cell Line Models for Preclinical Drug Evaluation Demonstrate Metastasis Inhibition by Dinaciclib through a Genome-Targeted Approach
Authors: Schott Courtney R. , Koehne Amanda L. , Sayles Leanne C. , Young Elizabeth P. , Luck Cuyler , Yu Katherine , Lee Alex G. , Breese Marcus R. , Leung Stanley G. , Xu Hang , Shah Avanthi Tayi , Liu Heng-Yi , Spillinger Aviv , Behroozfard Inge H. , Marini Kieren D. , Dinh Phuong T. , Pons Ventura María V. , Vanderboon Emma N. , Hazard Florette K. , Cho Soo-Jin , Avedian Raffi S. , Mohler David G. , Zimel Melissa , Wustrack Rosanna , Curtis Christina , Sirota Marina , Sweet-Cordero E. Alejandro
Published: February 2024

Copy number and count data for tumor suppressor genes and oncogenes in primary tumors, PDXs, and PDX-derived cell lines
Supplementary Table S5 from Therapy-Induced Senescence Contributes to the Efficacy of Abemaciclib in Patients with Dedifferentiated Liposarcoma
Authors: Gleason Caroline E. , Dickson Mark A. , Klein (Dooley) Mary E. , Antonescu Cristina R. , Gularte-Mérida Rodrigo , Benitez Marimar , Delgado Juliana I. , Kataru Raghu P. , Tan Mark Wei Yi , Bradic Martina , Adamson Travis E. , Seier Kenneth , Richards Allison L. , Palafox Marta , Chan Eric , D'Angelo Sandra P. , Gounder Mrinal M. , Keohan Mary Louise , Kelly Ciara M. , Chi Ping , Movva Sujana , Landa Jonathan , Crago Aimee M. , Donoghue Mark T.A. , Qin Li-Xuan , Serra Violetta , Turkekul Mesruh , Barlas Afsar , Firester Daniel M. , Manova-Todorova Katia , Mehrara Babak J. , Kovatcheva Marta , Tan Nguan Soon , Singer Samuel , Tap William D. , Koff Andrew
Published: February 2024

Transcript changes relative to quiescence
Supplementary Table S6 from Comparison of Circulating Tumor DNA Assays for Molecular Residual Disease Detection in Early-Stage Triple-Negative Breast Cancer
Authors: Coakley Maria , Villacampa Guillermo , Sritharan Prithika , Swift Claire , Dunne Kathryn , Kilburn Lucy , Goddard Katie , Pipinikas Christodoulos , Rojas Patricia , Emmett Warren , Hall Peter , Harper-Wynne Catherine , Hickish Tamas , Macpherson Iain , Okines Alicia , Wardley Andrew , Wheatley Duncan , Waters Simon , Palmieri Carlo , Winter Matthew , Cutts Rosalind J. , Garcia-Murillas Isaac , Bliss Judith , Turner Nicholas C.
Published: February 2024

Diagnostic performance of RaDaR assay at 24 months.
Supplementary Table S4 from Therapy-Induced Senescence Contributes to the Efficacy of Abemaciclib in Patients with Dedifferentiated Liposarcoma
Authors: Gleason Caroline E. , Dickson Mark A. , Klein (Dooley) Mary E. , Antonescu Cristina R. , Gularte-Mérida Rodrigo , Benitez Marimar , Delgado Juliana I. , Kataru Raghu P. , Tan Mark Wei Yi , Bradic Martina , Adamson Travis E. , Seier Kenneth , Richards Allison L. , Palafox Marta , Chan Eric , D'Angelo Sandra P. , Gounder Mrinal M. , Keohan Mary Louise , Kelly Ciara M. , Chi Ping , Movva Sujana , Landa Jonathan , Crago Aimee M. , Donoghue Mark T.A. , Qin Li-Xuan , Serra Violetta , Turkekul Mesruh , Barlas Afsar , Firester Daniel M. , Manova-Todorova Katia , Mehrara Babak J. , Kovatcheva Marta , Tan Nguan Soon , Singer Samuel , Tap William D. , Koff Andrew
Published: February 2024

Dose reductions in this study identified by individual patients
Supplementary Table S3 from Comparison of Circulating Tumor DNA Assays for Molecular Residual Disease Detection in Early-Stage Triple-Negative Breast Cancer
Authors: Coakley Maria , Villacampa Guillermo , Sritharan Prithika , Swift Claire , Dunne Kathryn , Kilburn Lucy , Goddard Katie , Pipinikas Christodoulos , Rojas Patricia , Emmett Warren , Hall Peter , Harper-Wynne Catherine , Hickish Tamas , Macpherson Iain , Okines Alicia , Wardley Andrew , Wheatley Duncan , Waters Simon , Palmieri Carlo , Winter Matthew , Cutts Rosalind J. , Garcia-Murillas Isaac , Bliss Judith , Turner Nicholas C.
Published: February 2024

Baseline information (n=141).
Supplementary Figure S9 from Therapy-Induced Senescence Contributes to the Efficacy of Abemaciclib in Patients with Dedifferentiated Liposarcoma
Authors: Gleason Caroline E. , Dickson Mark A. , Klein (Dooley) Mary E. , Antonescu Cristina R. , Gularte-Mérida Rodrigo , Benitez Marimar , Delgado Juliana I. , Kataru Raghu P. , Tan Mark Wei Yi , Bradic Martina , Adamson Travis E. , Seier Kenneth , Richards Allison L. , Palafox Marta , Chan Eric , D'Angelo Sandra P. , Gounder Mrinal M. , Keohan Mary Louise , Kelly Ciara M. , Chi Ping , Movva Sujana , Landa Jonathan , Crago Aimee M. , Donoghue Mark T.A. , Qin Li-Xuan , Serra Violetta , Turkekul Mesruh , Barlas Afsar , Firester Daniel M. , Manova-Todorova Katia , Mehrara Babak J. , Kovatcheva Marta , Tan Nguan Soon , Singer Samuel , Tap William D. , Koff Andrew
Published: February 2024

Enforced expression of ANGPTL4 can induce stable growth arrest and SASP gene expression in A549 cells treated with palbociclib
Supplementary Figure S1 from Comparison of Circulating Tumor DNA Assays for Molecular Residual Disease Detection in Early-Stage Triple-Negative Breast Cancer
Authors: Coakley Maria , Villacampa Guillermo , Sritharan Prithika , Swift Claire , Dunne Kathryn , Kilburn Lucy , Goddard Katie , Pipinikas Christodoulos , Rojas Patricia , Emmett Warren , Hall Peter , Harper-Wynne Catherine , Hickish Tamas , Macpherson Iain , Okines Alicia , Wardley Andrew , Wheatley Duncan , Waters Simon , Palmieri Carlo , Winter Matthew , Cutts Rosalind J. , Garcia-Murillas Isaac , Bliss Judith , Turner Nicholas C.
Published: February 2024

Correlation between the tumor fraction percentage as reported by mean Variant Allele Frequency (mean VAF) or estimated Variant Allele Frequency (eVAF) for the RaDaR ctDNA assay.
Supplementary Figure S2 from Therapy-Induced Senescence Contributes to the Efficacy of Abemaciclib in Patients with Dedifferentiated Liposarcoma
Authors: Gleason Caroline E. , Dickson Mark A. , Klein (Dooley) Mary E. , Antonescu Cristina R. , Gularte-Mérida Rodrigo , Benitez Marimar , Delgado Juliana I. , Kataru Raghu P. , Tan Mark Wei Yi , Bradic Martina , Adamson Travis E. , Seier Kenneth , Richards Allison L. , Palafox Marta , Chan Eric , D'Angelo Sandra P. , Gounder Mrinal M. , Keohan Mary Louise , Kelly Ciara M. , Chi Ping , Movva Sujana , Landa Jonathan , Crago Aimee M. , Donoghue Mark T.A. , Qin Li-Xuan , Serra Violetta , Turkekul Mesruh , Barlas Afsar , Firester Daniel M. , Manova-Todorova Katia , Mehrara Babak J. , Kovatcheva Marta , Tan Nguan Soon , Singer Samuel , Tap William D. , Koff Andrew
Published: February 2024

Patient toxicities graded according to the National Cancer Institute's common terminology criteria for adverse events, version 4.0
Supplementary Figure S10 from Therapy-Induced Senescence Contributes to the Efficacy of Abemaciclib in Patients with Dedifferentiated Liposarcoma
Authors: Gleason Caroline E. , Dickson Mark A. , Klein (Dooley) Mary E. , Antonescu Cristina R. , Gularte-Mérida Rodrigo , Benitez Marimar , Delgado Juliana I. , Kataru Raghu P. , Tan Mark Wei Yi , Bradic Martina , Adamson Travis E. , Seier Kenneth , Richards Allison L. , Palafox Marta , Chan Eric , D'Angelo Sandra P. , Gounder Mrinal M. , Keohan Mary Louise , Kelly Ciara M. , Chi Ping , Movva Sujana , Landa Jonathan , Crago Aimee M. , Donoghue Mark T.A. , Qin Li-Xuan , Serra Violetta , Turkekul Mesruh , Barlas Afsar , Firester Daniel M. , Manova-Todorova Katia , Mehrara Babak J. , Kovatcheva Marta , Tan Nguan Soon , Singer Samuel , Tap William D. , Koff Andrew
Published: February 2024

Increases in ANGPTL4 are not associated with palbociclib induced senescence in ER+ breast cancer cell lines
Data from PD-1 Expression on Intratumoral Regulatory T Cells Is Associated with Lack of Benefit from Anti–PD-1 Therapy in Metastatic Clear-Cell Renal Cell Carcinoma Patients
Authors: Denize Thomas , Jegede Opeyemi A. , Matar Sayed , El Ahmar Nourhan , West Destiny J. , Walton Emily , Bagheri Aseman Sheshdeh , Savla Varunika , Nabil Laimon Yasmin , Gupta Saurabh , Vemula Sai Vikram , Braun David A. , Burke Kelly P. , Catalano Paul J. , Freeman Gordon J. , Motzer Robert J. , Atkins Michael B. , McDermott David F. , Sharpe Arlene H. , Choueiri Toni K. , Signoretti Sabina
Published: February 2024

AbstractPurpose:
Programmed cell death protein 1 (PD-1) expression on CD8+TIM-3−LAG-3− tumor-infiltrating cells predicts positive response to PD-1 blockade in metastatic clear-cell renal cell carcinoma (mccRCC). Because inhibition of PD-1 signaling in regulatory T cells (Treg) augments their immunosuppressive function, we hypothesized that PD-1 expression on tumor-infiltrating Tregs would predict resistance to PD-1 inhibitors.
Experimental Design:
PD-1+ Tregs were phenotyped using multiparametric immunofluorescence in ccRCC tissues from the CheckMate-025 trial (nivolumab: n = 91; everolimus: n = 90). Expression of CD8, PD-1, TIM-3, and LAG-3 was previously determined (Ficial and colleagues, 2021). Clinical endpoints included progression-free survival (PFS), overall survival (OS), and objective response rate (ORR).
Results:
In the nivolumab (but not everolimus) arm, high percentage of PD-1+ Tregs was associated with shorter PFS (3.19 vs. 5.78 months; P = 0.021), shorter OS (18.1 vs. 27.7 months; P = 0.013) and marginally lower ORR (12.5% vs. 31.3%; P = 0.059). An integrated biomarker (PD-1 Treg/CD8 ratio) was developed by calculating the ratio between percentage of PD-1+Tregs (marker of resistance) and percentage of CD8+PD-1+TIM-3−LAG-3− cells (marker of response). In the nivolumab (but not everolimus) arm, patients with high PD-1 Treg/CD8 ratio experienced shorter PFS (3.48 vs. 9.23 months; P < 0.001), shorter OS (18.14 vs. 38.21 months; P < 0.001), and lower ORR (15.69% vs. 40.00%; P = 0.009). Compared with the individual biomarkers, the PD-1 Treg/CD8 ratio showed improved ability to predict outcomes to nivolumab versus everolimus.
Conclusions:
PD-1 expression on Tregs is associated with resistance to PD-1 blockade in mccRCC, suggesting that targeting Tregs may synergize with PD-1 inhibition. A model that integrates PD-1 expression on Tregs and CD8+TIM-3−LAG-3− cells has higher predictive value.
Data from Phase Ia/b Study of Giredestrant ± Palbociclib and ± Luteinizing Hormone-Releasing Hormone Agonists in Estrogen Receptor–Positive, HER2-Negative, Locally Advanced/Metastatic Breast Cancer
Authors: Jhaveri Komal L. , Bellet Meritxell , Turner Nicholas C. , Loi Sherene , Bardia Aditya , Boni Valentina , Sohn Joohyuk , Neilan Tomas G. , Villanueva-Vázquez Rafael , Kabos Peter , García-Estévez Laura , López-Miranda Elena , Pérez-Fidalgo J. Alejandro , Pérez-García Jose M. , Yu Jiajie , Fredrickson Jill , Moore Heather M. , Chang Ching-Wei , Bond John W. , Eng-Wong Jennifer , Gates Mary R. , Lim Elgene
Published: February 2024

AbstractPurpose:
Giredestrant is an investigational next-generation, oral, selective estrogen receptor antagonist and degrader for the treatment of estrogen receptor–positive (ER+) breast cancer. We present the primary analysis results of the phase Ia/b GO39932 study (NCT03332797).
Patients and Methods:
Patients with ER+, HER2-negative locally advanced/metastatic breast cancer previously treated with endocrine therapy received single-agent giredestrant (10, 30, 90, or 250 mg), or giredestrant (100 mg) ± palbociclib 125 mg ± luteinizing hormone-releasing hormone (LHRH) agonist. Detailed cardiovascular assessment was conducted with giredestrant 100 mg. Endpoints included safety (primary), pharmacokinetics, pharmacodynamics, and efficacy.
Results:
As of January 28, 2021, with 175 patients enrolled, no dose-limiting toxicity was observed, and the MTD was not reached. Adverse events (AE) related to giredestrant occurred in 64.9% and 59.4% of patients in the single-agent ± LHRH agonist and giredestrant + palbociclib ± LHRH agonist cohorts, respectively (giredestrant-only–related grade 3/4 AEs were reported in 4.5% of patients across the single-agent cohorts and 3.1% of those with giredestrant + palbociclib). Dose-dependent asymptomatic bradycardia was observed, but no clinically significant changes in cardiac-related outcomes: heart rate, blood pressure, or exercise duration. Clinical benefit was observed in all cohorts (48.6% of patients in the single-agent cohort and 81.3% in the giredestrant + palbociclib ± LHRH agonist cohort), with no clear dose relationship, including in patients with ESR1-mutated tumors.
Conclusions:
Giredestrant was well tolerated and clinically active in patients who progressed on prior endocrine therapy. Results warrant further evaluation of giredestrant in randomized trials in early- and late-stage ER+ breast cancer.
Data from Development of a Practical Nomogram for Personalized Anemia Management in Patients Treated with Ataxia Telangiectasia and Rad3-related Inhibitor Camonsertib
Authors: Rosen Ezra , Yap Timothy A. , Lee Elizabeth K. , Højgaard Martin , Mettu Niharika B. , Lheureux Stephanie , Carneiro Benedito A. , Plummer Ruth , Fretland Adrian J. , Ulanet Danielle , Xu Yi , McDougall Robin , Koehler Maria , Fontana Elisa
Published: February 2024

AbstractPurpose:
Camonsertib is a highly selective and potent inhibitor of ataxia telangiectasia and Rad3-related (ATR) kinase. Dose-dependent anemia is a class-related on-target adverse event often requiring dose modifications. Individual patient risk factors for the development of significant anemia complicate the selection of a “one-size-fits-all” ATR inhibitor (ATRi) dose and schedule, possibly leading to suboptimal therapeutic doses in patients at low risk of anemia. We evaluated whether early predictors of anemia could be identified to ultimately inform a personalized dose-modification approach.
Patients and Methods:
On the basis of preclinical observations and a mechanistic understanding of ATRi-related anemia, we identified several potential factors to explore in a multivariable linear regression modeling tool for predicting hemoglobin level ahead of day 22 (cycle 2) of treatment.
Results:
In patients treated with camonsertib monotherapy (NCT04497116), we observed that hemoglobin decline is consistently preceded by reticulocytopenia, and dose- and exposure-dependent decreases in monocytes. We developed a nomogram incorporating baseline and day 8 hemoglobin and reticulocyte values that predicted the day 22 hemoglobin values of patients with clinically valuable concordance (within 7.5% of observations) 80% of the time in a cross-validation performance test of data from 60 patients.
Conclusions:
The prediction of future hemoglobin decrease, after a week of treatment, may enable a personalized, early dose modification to prevent development of clinically significant anemia and resulting unscheduled dose holds or transfusions.
Data from First-Line Ipatasertib, Atezolizumab, and Taxane Triplet for Metastatic Triple-Negative Breast Cancer: Clinical and Biomarker Results
Authors: Schmid Peter , Turner Nicholas C. , Barrios Carlos H. , Isakoff Steven J. , Kim Sung-Bae , Sablin Marie-Paule , Saji Shigehira , Savas Peter , Vidal Gregory A. , Oliveira Mafalda , O'Shaughnessy Joyce , Italiano Antoine , Espinosa Enrique , Boni Valentina , White Shane , Rojas Beatriz , Freitas-Junior Ruffo , Chae Yeesoo , Bondarenko Igor , Lee Jieun , Torres Mattos Cesar , Martinez Rodriguez Jorge Luis , Lam Lisa H. , Jones Surai , Reilly Sarah-Jayne , Huang Xiayu , Shah Kalpit , Dent Rebecca
Published: February 2024

AbstractPurpose:
To evaluate a triplet regimen combining immune checkpoint blockade, AKT pathway inhibition, and (nab-) paclitaxel as first-line therapy for locally advanced/metastatic triple-negative breast cancer (mTNBC).
Patients and Methods:
The single-arm CO40151 phase Ib study (NCT03800836), the single-arm signal-seeking cohort of IPATunity130 (NCT03337724), and the randomized phase III IPATunity170 trial (NCT04177108) enrolled patients with previously untreated mTNBC. Triplet therapy comprised intravenous atezolizumab 840 mg (days 1 and 15), oral ipatasertib 400 mg/day (days 1–21), and intravenous paclitaxel 80 mg/m2 (or nab-paclitaxel 100 mg/m2; days 1, 8, and 15) every 28 days. Exploratory translational research aimed to elucidate mechanisms and molecular markers of sensitivity and resistance.
Results:
Among 317 patients treated with the triplet, efficacy ranged across studies as follows: median progression-free survival (PFS) 5.4 to 7.4 months, objective response rate 44% to 63%, median duration of response 5.6 to 11.1 months, and median overall survival 15.7 to 28.3 months. The safety profile was consistent with the known toxicities of each agent. Grade ≥3 adverse events were more frequent with the triplet than with doublets or single-agent paclitaxel. Patients with PFS >10 months were characterized by NF1, CCND3, and PIK3CA alterations and increased immune pathway activity. PFS <5 months was associated with CDKN2A/CDKN2B/MTAP alterations and lower predicted phosphorylated AKT-S473 levels.
Conclusions:
In patients with mTNBC receiving an ipatasertib/atezolizumab/taxane triplet regimen, molecular characteristics may identify those with particularly favorable or unfavorable outcomes, potentially guiding future research efforts.
Data from Functional Contribution and Clinical Implication of Cancer-Associated Fibroblasts in Glioblastoma
Authors: Galbo Phillip M. , Madsen Anne Tranberg , Liu Yang , Peng Mou , Wei Yao , Ciesielski Michael J. , Fenstermaker Robert A. , Graff Sarah , Montagna Cristina , Segall Jeffrey E. , Sidoli Simone , Zang Xingxing , Zheng Deyou
Published: February 2024

AbstractPurpose:
The abundance and biological contribution of cancer-associated fibroblasts (CAF) in glioblastoma (GBM) are poorly understood. Here, we aim to uncover its molecular signature, cellular roles, and potential tumorigenesis implications.
Experimental Design:
We first applied single-cell RNA sequencing (RNA-seq) and bioinformatics analysis to identify and characterize stromal cells with CAF transcriptomic features in human GBM tumors. Then, we performed functional enrichment analysis and in vitro assays to investigate their interactions with malignant GBM cells.
Results:
We found that CAF abundance was low but significantly correlated with tumor grade, poor clinical outcome, and activation of extracellular matrix remodeling using three large cohorts containing bulk RNA-seq data and clinical information. Proteomic analysis of a GBM-derived CAF line and its secretome revealed fibronectin (FN1) as a critical candidate factor mediating CAF functions. This was validated using in vitro cellular models, which demonstrated that CAF-conditioned media and recombinant FN1 could facilitate the migration and invasion of GBM cells. In addition, we showed that CAFs were more abundant in the mesenchymal-like state (or subtype) than in other states of GBMs. Interestingly, cell lines resembling the proneural state responded to the CAF signaling better for the migratory and invasive phenotypes.
Conclusions:
Overall, this study characterized the molecular features and functional impacts of CAFs in GBM, alluding to novel cell interactions mediated by CAFs in the GBM microenvironment.
Data from A Composite Decision Rule of CD8+ T-cell Density in Tumor Biopsies Predicts Efficacy in Early-stage, Immunotherapy Trials
Authors: Dejardin David , Kraxner Anton , Blank Annika , Rieder Natascha , Teichgräber Volker , Städler Nicolas , Beyer Ulrich , Gomes Bruno , Charo Jehad
Published: February 2024

AbstractPurpose:
To examine whether CD8+ T-cell numbers in paired tumor biopsies in early-stage clinical trials can be used as an early indicator of clinical benefit for cancer immunotherapies.
Experimental Design:
Paraffin sections of tumor biopsies were stained immunohistochemically for CD8+ T cells, which were digitally enumerated. The tumor biopsies were from cancer patients in early-phase trials testing novel immunotherapeutic agents. Paired biopsies taken before the start of treatment and on-treatment were compared. A total of 155 patients were used as the training set and an additional 221 patients were used as the validation set.
Results:
Using the Cox proportional hazard model, a ≥0.9- increase in fold change (FC) on a ln scale in CD8+ T cells (corresponding to a 2.5-fold increase on the linear scale), from baseline, demonstrated a greater association with prolonged progression-free survival and allowed improved differentiation between groups above and below the threshold. Similarly, a ≥6.2 threshold in geometric mean of the on-treatment density (OTD) of T cells, which approximately corresponds to 500 cells/mm2, correlated with longer PFS. The combination of both criteria (FC and OTD) provided the best discrimination between clinically nonactive and active compounds.
Conclusions:
We propose that a composite score of CD8+ T-cell density in paired biopsies taken before and on-treatment may be a new biomarker to inform on clinical outcomes in early immunotherapy clinical trials.
Triple Primary Cancers: An Analysis of Genetic and Environmental Factors
Authors: Borja Nicholas A. , Silva-Smith Rachel , Calfa Carmen , Sussman Daniel A. , Tekin Mustafa
Published: February 2024

The occurrence of multiple primary cancers (MPC) is thought to reflect increased cancer susceptibility in patients due to a combination of genetic and environmental factors. Here we conducted a retrospective review of 2,894 consecutive patients evaluated at a single institution and identified 31 (1.14%) individuals with a history of three or more primary cancers, then analyzed the genetic and environmental influences associated with their propensity for developing malignancies. We found that 35.5% of patients had a hereditary cancer syndrome (HCS), with high penetrance HCS in 72.7% of cases, suggesting that monogenic causes underly a significant proportion of triple primary cancer risk. Analysis of cancer frequencies found that the diagnosis of breast cancer was associated with a significantly lower likelihood of HCS, while the diagnosis of colorectal, prostate, and pancreas cancer was associated with a significantly higher likelihood of HCS. Comparison of HCS-positive and HCS-negative patients revealed similar demographic characteristics, mean age at first diagnosis, and family history of cancer. Moreover, no significant differences in lifestyle behaviors, occupational exposures, chronic health conditions, or treatment with chemotherapy and radiation were observed between HCS-positive and -negative groups, though outliers in tobacco smoking, as well as systemic treatment after both first and second primary cancers were observed. These findings indicate a robust contribution of HCS to cancer susceptibility among patients with triple primary cancers while environmental influences were less evident. This emphasizes the need for larger MPC cohorts incorporating additional genetic and environmental factors to more comprehensively characterize drivers of cancer risk.

Prevention Relevance:

In patients with three or more primary cancers, genetic predisposition explained a significant proportion of cases; however, treatment history, lifestyle habits, and other exposures appeared to play a less significant role. This highlights the value of early genetic screening and the need to develop more sensitive markers of cancer susceptibility.

See related Spotlight, p. 193
Supplementary Table S1 from Pim Kinase Inhibitors Increase Gilteritinib Cytotoxicity in FLT3-ITD Acute Myeloid Leukemia Through GSK-3β Activation and c-Myc and Mcl-1 Proteasomal Degradation
Authors: Lee Jonelle K. , Chatterjee Aditi , Scarpa Mario , Bailey Christopher M. , Niyongere Sandrine , Singh Prerna , Mustafa Ali Moaath K. , Kapoor Shivani , Wang Yin , Silvestri Giovannino , Baer Maria R.
Published: February 2024

Clinical information on patients with AML with FLT3-ITD whose samples were studied.
FIGURE 6 from Pim Kinase Inhibitors Increase Gilteritinib Cytotoxicity in FLT3-ITD Acute Myeloid Leukemia Through GSK-3β Activation and c-Myc and Mcl-1 Proteasomal Degradation
Authors: Lee Jonelle K. , Chatterjee Aditi , Scarpa Mario , Bailey Christopher M. , Niyongere Sandrine , Singh Prerna , Mustafa Ali Moaath K. , Kapoor Shivani , Wang Yin , Silvestri Giovannino , Baer Maria R.
Published: February 2024

S159A-mutated Mcl-1 confers resistance to Mcl-1 downregulation and to apoptosis induction by gilteritinib and AZD1208 combination treatment. A, Ba/F3-ITD cells infected with pBabe-Flag hMcl-1-S159A, containing Mcl-1 with a mutation changing serine to alanine at residue 159, preventing phosphorylation, pBabe-Flag hMcl-1 plasmid, containing wild-type Mcl-1, or pBABE-puro empty vector were treated with either gilteritinib and AZD1208 or DMSO control, and serial samples were immunoblotted for Mcl-1 and vinculin loading control. Densitometric analysis is also shown. B, To measure Mcl-1 protein turnover, cells were pretreated with CHX for 1 hour and then treated with gilteritinib and AZD1208 (+) or DMSO control (−). Serial samples were immunoblotted for c-Myc and vinculin loading control. Densitometric analysis was performed. Mcl-1 was normalized to vinculin and 50% protein turnover timepoints were determined to be 1.75 versus more than 2 hours for gilteritinib and AZD1208 versus DMSO control for empty vector, 1.27 versus 1.6 for wild-type Mcl-1 and more than 2 hours for both for S159A Mcl-1. C, Cells infected with pBabe-Flag hMcl-1-S159A, pBabe-Flag hMcl-1 or pBABE-puro empty vector control were treated with gilteritinib and/or AZD1208, or DMSO control, for 48 hours, and apoptosis was measured. Apoptosis induction by gilteritinib and AZD1208 combination was significantly reduced in cells infected with pBABE-puroS159A compared with empty vector control (**, P < 0.001).
FIGURE 5 from Pim Kinase Inhibitors Increase Gilteritinib Cytotoxicity in FLT3-ITD Acute Myeloid Leukemia Through GSK-3β Activation and c-Myc and Mcl-1 Proteasomal Degradation
Authors: Lee Jonelle K. , Chatterjee Aditi , Scarpa Mario , Bailey Christopher M. , Niyongere Sandrine , Singh Prerna , Mustafa Ali Moaath K. , Kapoor Shivani , Wang Yin , Silvestri Giovannino , Baer Maria R.
Published: February 2024

T58A-mutated c-Myc confers resistance to c-Myc downregulation and to apoptosis induction by gilteritinib and AZD1208 combination treatment. A, Ba/F3-ITD cells infected with pCDH-MSCV-MycT58A-EF1a-copGFP, containing c-Myc with a mutation changing threonine to alanine at residue 58, preventing phosphorylation, pCDH-MSCV-Myc(WT)-EF1a-copGFP, containing wild-type c-Myc, or pCDH-MSCV-MCS-EF1-copGFP empty vector were treated with either gilteritinib and AZD1208 or DMSO control and serial samples were immunoblotted for c-Myc and vinculin loading control. Densitometric analysis is also shown. B, To measure c-Myc protein turnover, cells were pretreated with CHX for 1 hour and then treated with gilteritinib and AZD1208 (+) or DMSO control (−). Serial samples were immunoblotted for c-Myc and vinculin loading control. Densitometry was performed. c-Myc was normalized to vinculin and 50% protein turnover timepoints were determined to be 1.035 versus 1.2 hours for gilteritinib and AZD1208 versus DMSO control for empty vector, 0.6 versus 0.72 for wild-type c-Myc and more than 2 hours for both for T58A c-Myc. C, Cells infected with pCDH-MSCV-MycT58A-EF1a-copGFP, pCDH-MSCV-Myc(WT)-EF1a-copGFP or pCDH-MSCV-MCS-EF1-copGFP empty vector were treated with gilteritinib and/or AZD1208, or DMSO control, for 48 hours, and apoptosis was measured. Apoptosis induction by gilteritinib and AZD1208 combination was significantly reduced in cells infected with pMSCVpuro-Flag-cMyc T58A, compared with empty vector control (***, P <0.0001).
Data from Pim Kinase Inhibitors Increase Gilteritinib Cytotoxicity in FLT3-ITD Acute Myeloid Leukemia Through GSK-3β Activation and c-Myc and Mcl-1 Proteasomal Degradation
Authors: Lee Jonelle K. , Chatterjee Aditi , Scarpa Mario , Bailey Christopher M. , Niyongere Sandrine , Singh Prerna , Mustafa Ali Moaath K. , Kapoor Shivani , Wang Yin , Silvestri Giovannino , Baer Maria R.
Published: February 2024

Abstract
Acute myeloid leukemia (AML) with fms-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) has poor outcomes. FLT3-ITD drives constitutive and aberrant FLT3 signaling, activating STAT5 and upregulating the downstream oncogenic serine/threonine kinase Pim-1. FLT3 inhibitors are in clinical use, but with limited and transient efficacy. We previously showed that concurrent treatment with Pim and FLT3 inhibitors increases apoptosis induction in FLT3-ITD–expressing cells through posttranslational downregulation of Mcl-1. Here we further elucidate the mechanism of action of this dual targeting strategy. Cytotoxicity, apoptosis and protein expression and turnover were measured in FLT3-ITD–expressing cell lines and AML patient blasts treated with the FLT3 inhibitor gilteritinib and/or the Pim inhibitors AZD1208 or TP-3654. Pim inhibitor and gilteritinib cotreatment increased apoptosis induction, produced synergistic cytotoxicity, downregulated c-Myc protein expression, earlier than Mcl-1, increased turnover of both proteins, which was rescued by proteasome inhibition, and increased efficacy and prolonged survival in an in vivo model. Gilteritinib and Pim inhibitor cotreatment of Ba/F3-ITD cells infected with T58A c-Myc or S159A Mcl-1 plasmids, preventing phosphorylation at these sites, did not downregulate these proteins, increase their turnover or increase apoptosis induction. Moreover, concurrent treatment with gilteritinib and Pim inhibitors dephosphorylated (activated) the serine/threonine kinase glycogen synthase kinase-3β (GSK-3β), and GSK-3β inhibition prevented c-Myc and Mcl-1 downregulation and decreased apoptosis induction. The data are consistent with c-Myc T58 and Mcl-1 S159 phosphorylation by activated GSK-3β as the mechanism of action of gilteritinib and Pim inhibitor combination treatment, further supporting GSK-3β activation as a therapeutic strategy in FLT3-ITD AML.
Significance:
FLT3-ITD is present in 25% of in AML, with continued poor outcomes. Combining Pim kinase inhibitors with the FDA-approved FLT3 inhibitor gilteritinib increases cytotoxicity in vitro and in vivo through activation of GSK-3β, which phosphorylates and posttranslationally downregulates c-Myc and Mcl-1. The data support efficacy of GSK-3β activation in FLT3-ITD AML, and also support development of a clinical trial combining the Pim inhibitor TP-3654 with gilteritinib.
Cumulative Incidence, Risk Factors, and Overall Survival of Disease Recurrence after Curative Resection of Stage II–III Colorectal Cancer: A Population-based Study
Authors: Boute Tara C. , Swartjes Hidde , Greuter Marjolein J.E. , Elferink Marloes A.G. , van Eekelen Rik , Vink Geraldine R. , de Wilt Johannes H.W. , Coupé Veerle M.H.
Published: February 2024

Real-world data are necessitated to counsel patients about the risk for recurrent disease after curative treatment of colorectal cancer. This study provided a population-based overview of the epidemiology of recurrent disease in patients with surgically resected stage II/III colorectal cancer.

Patients diagnosed with stage II/III primary colorectal cancer between July and December 2015 were selected from the Netherlands Cancer Registry (N = 3,762). Cumulative incidence of recurrent disease was estimated, and multivariable competing risk regression was used to identify risk factors for recurrent disease in patients with primary colon and rectal cancer. Moreover, overall survival (OS) after diagnosis of recurrent colorectal cancer was estimated.

Median clinical follow-up was 58 months (Q1–Q3: 22–62). Five-year cumulative incidence of recurrent disease was 21.6% [95% confidence interval (CI): 20.0–23.2] and 30.0% (95% CI: 28.3–33.5) for patients with primary colon and rectal cancer, respectively. Stage III disease and incomplete resection margin in patients with primary colon cancer and extramural vascular invasion in patients with primary rectal cancer were strongly (HR ≥ 2) associated with recurrent disease. Median OS of patients with distant, locoregional, or the synchronous combination of distant and locoregional recurrent disease was 29, 27, and 13 months, respectively (P < 0.001). Patients with distant recurrences limited to liver or lung showed a median OS of 46 and 48 months, respectively. The incidence of recurrent disease was higher in patients with rectal cancer than in patients with colon cancer, predominantly due to higher rates of distant recurrences. OS after recurrent disease was impaired, but subgroups of patients diagnosed with recurrent disease limited to one site showed statistically significantly longer OS.

Significance:

Population-based data on recurrent colorectal cancer are rare, but crucial for counseling patients and their physicians. This large nationwide, population-based study provides an up-to-date overview of the epidemiology of recurrent disease in patients with stage II and III primary colon and rectal cancer treated with surgical resection.
Cancer-associated Fibroblast–specific Expression of the Matricellular Protein CCN1 Coordinates Neovascularization and Stroma Deposition in Melanoma Metastasis
Authors: Hutchenreuther James , Nguyen John , Quesnel Katherine , Vincent Krista M. , Petitjean Louis , Bourgeois Sophia , Boyd Mark , Bou-Gharios George , Postovit Lynne-Marie , Leask Andrew
Published: February 2024

Melanoma is the leading cause of skin cancer–related death. As prognosis of patients with melanoma remains problematic, identification of new therapeutic targets remains essential. Matricellular proteins are nonstructural extracellular matrix proteins. They are secreted into the tumor microenvironment to coordinate behavior among different cell types, yet their contribution to melanoma is underinvestigated. Examples of matricellular proteins include those comprising the CCN family. The CCN family member, CCN1, is highly proangiogenic. Herein, we show that, in human patients with melanoma, although found in several tumor cell types, CCN1 is highly expressed by a subset of cancer-associated fibroblasts (CAF) in patients with melanoma and this expression correlates positively with expression of proangiogenic genes and progressive disease/resistance to anti-PD1 checkpoint inhibitors. Consistent with these observations, in a syngeneic C57BL6 mouse model of melanoma, loss of CCN1 expression from Col1A2-Cre-, herein identified as “universal,” fibroblasts, impaired metastasis of subcutaneously injected B16F10 tumor cells to lung, concomitant with disrupted neovascularization and collagen organization. Disruption of the extracellular matrix in the loss of CCN1 was validated using a novel artificial intelligence–based image analysis platform that revealed significantly decreased phenotypic fibrosis and composite morphometric collagen scores. As drug resistance is linked to matrix deposition and neoangiogenesis, these data suggest that CCN1, due to its multifaceted role, may represent a novel therapeutic target for drug-resistant melanoma. Our data further emphasize the essential role that cancer-associated, (universal) Col1A2-Cre-fibroblasts and extracellular matrix remodeling play in coordinating behavior among different cell types within the tumor microenvironment.

Significance:

In human patients, the expression of proangiogenic matricellular protein CCN1 in CAFs correlates positively with expression of stroma and angiogenic markers and progressive disease/resistance to checkpoint inhibitor therapy. In an animal model, loss of CCN1 from CAFs impaired metastasis of melanoma cells, neovascularization, and collagen deposition, emphasizing that CAFs coordinate cellular behavior in a tumor microenvironment and that CCN1 may be a novel target.
Relapsed IgA Multiple Myeloma as Testicular Plasmacytoma after Quadrable Novel Therapy and Autologous Stem Cell Transplant: A Rare Case Report and Literature Review
Authors: Abdulgayoom Mohammed , Soliman Dina , Helmy Abbas , Haroon Athar , Telfah Husam , Ghasoub Rola , Fareed Shehab , Elsabah Hesham
Published: February 2024

Introduction: Multiple myeloma (MM) is a clonal neoplasm of plasma cells that may manifest as an extramedullary disease in rare cases. Case Report: In this case report, we present the rare occurrence of testicular relapse in a 39-year-old patient with IgA MM after 3 years of remission. We discuss the clinical course and management of this unusual presentation and provide a comprehensive literature review of testicular involvement by MM. Conclusion: Despite advances in MM treatment, relapse remains common, highlighting the importance of careful follow-up and timely detection of disease recurrence at atypical sites. This case highlights the need for further research to standardize the diagnosis and treatment of testicular MM.
Transformer faults identification via fuzzy logic approach
Authors: Dapshima Babagana Ali , Mishra Renu , Tyagi Priyanka
Published: February 2024

The need for a constant electricity supply is at an alarming rate especially in the 21st century due to the high rate of increase in industrialization across the globe. Conventional protection schemes such as differential relays, Buchholz relay, and other techniques such as genetic algorithms and artificial neural networks, do not match the precision and reliability needed for transformer fault indentification, due to their complexity in computation, tedious training system, time consumption, and need the of human experts. The method proposed in this research is the use of a fuzzy inference system in detecting potential faults in power system transformers. The faults in the transformer were observed and analyzed using a simulation system of MATLAB/Simulink software. The suggested approach ensures swift identification of faults as it relies on if-then rules and only uses current and voltage measurements with 100% independence toward the power flow direction, making it highly reliable and simple to implement compared to other techniques for transformer fault identification.
Enhanced proportional integral controller for DSTATCOM with particle swarm optimization algorithm in power system
Authors: Datar Parag Vijay , Kulkarni Deepak Balkrishna
Published: February 2024

Power system expansion planning is supported by using distributed generation (DG) instead of installing new main power system generators. The portability and autonomous operation of the DG make it capable of integrating into the distribution system. Power electronics devices for home loads, mainly electric vehicles, mobile phones, and laptops, introduce harmonics and related power quality issues to the distribution system. This load creates power quality issues like an increase in total harmonic distortion (THD) and a reduction in power factor. This paper uses the DG to supply important power electronics devices for the mitigation of power quality problems in distributed systems with non-linear loads, such as electric vehicles, called the “distributed static compensator (DSTATCOM)”. Wind and photovoltaic (PV) generators supply power to a common DC source. To improve power quality D-STATCOM powered by PV and wind energy systems at the DC link is incorporated. The direct axis/quadrature axis method (DQ method) controls the real and reactive components of the power. Proportional integral (PI) and particle swarm optimization (PSO) based PI controller parameter estimation are developed, and results are compared for power quality performance. In terms of improving power quality, the PSO-based parameter estimate of the PI controller performs better than the traditional PI controller.

 
Deep transfer learning model for brain tumor segmentation and classification using UNet and chopped VGGNet
Authors: Shedbalkar Jayashree , Prabhushetty Kappargaon
Published: February 2024

Brain tumors (BT) are a leading cause of cancer-related mortality worldwide, underscoring the critical need for early and precise detection to improve patient survival rates. Computer-aided diagnosis (CAD) plays a pivotal role in early BT detection by providing medical experts with valuable information image analysis. Various researchers have developed distinct methodologies, drawing from both machine and deep learning approaches. ML relies on manual feature analysis, which entails a time-intensive procedure of selecting an optimal feature extractor and necessitates domain experts with a deep understanding of feature selection. Conversely, deep learning methods exhibit superior performance compared to ML owing to their end-to-end, automated, high-level, and robust attribute mining capabilities. In this study introduced an innovative two-stage framework designed for the automatic classification of BT. In the initial stage, utilize U-Net models to conduct BT segmentation as part of the pre-processing step. Subsequently, in the second stage, utilize the improved BT images as input for a transfer learning-based model known as visual geometry group neural network (VGGNet), which excels in BT classification. The experimental analysis shows that the proposed approach has reported the average classification accuracy as 98.6%, 98.76%, and 99.45% for Meningioma, Glioma, and Pituitary BTs, respectively.