bluuebunny/crossref_metadata_2025 huggingface dataset:
Supplemental Figure 2 from Early Changes in Circulating Cell-Free KRAS G12C Predict Response to Adagrasib in KRAS Mutant Non–Small Cell Lung Cancer Patients
Authors: Paweletz Cloud P. , Heavey Grace A. , Kuang Yanan , Durlacher Emily , Kheoh Thian , Chao Richard C. , Spira Alexander I. , Leventakos Konstantinos , Johnson Melissa L. , Ou Sai-Hong Ignatius , Riely Gregory J. , Anderes Kenna , Yang Wenjing , Christensen James G. , Jänne Pasi A.
Published: August 2023

Supplemental Figure 2: Baseline AF% vs sum of diameter (SOD) at baseline.
Figure S10 from BBT-176, a Novel Fourth-Generation Tyrosine Kinase Inhibitor for Osimertinib-Resistant EGFR Mutations in Non–Small Cell Lung Cancer
Authors: Lim Sun Min , Fujino Toshio , Kim Chulwon , Lee Gwanghee , Lee Yong-Hee , Kim Dong-Wan , Ahn Jin Seok , Mitsudomi Tetsuya , Jin Taiguang , Lee Sang-Yoon
Published: August 2023

Supplementary Figure 10. Growth inhibition by BBT-176 with and without osimertinib in BBT-176-resistant clones of EGFR 19Del/C797S (A) and EGFR 19Del/T790M/C797S (B) mutants. C, IC50 values for BBT-176 with and without osimertinib in BBT-176-resistant clones. IC50 values in nM were measured 3 days later and cell growth was plotted relative to untreated control cells (mean ± SD). Abbreviation: BR(1/2), BBT-176-resistant (clone 1/2).
Figure S1 from BBT-176, a Novel Fourth-Generation Tyrosine Kinase Inhibitor for Osimertinib-Resistant EGFR Mutations in Non–Small Cell Lung Cancer
Authors: Lim Sun Min , Fujino Toshio , Kim Chulwon , Lee Gwanghee , Lee Yong-Hee , Kim Dong-Wan , Ahn Jin Seok , Mitsudomi Tetsuya , Jin Taiguang , Lee Sang-Yoon
Published: August 2023

Supplementary Figure 1. Growth inhibition by BBT-176 with and without cetuximab in EGFR 19Del and EGFR L858R-derived mutants. Abbreviation: N/E, not evaluable.
Supplementary Table S4 from Osimertinib and Selpercatinib Efficacy, Safety, and Resistance in a Multicenter, Prospectively Treated Cohort of EGFR-Mutant and RET Fusion-Positive Lung Cancers
Authors: Rotow Julia , Patel Jyoti D. , Hanley Matthew P. , Yu Helena , Awad Mark , Goldman Jonathan W. , Nechushtan Hovav , Scheffler Matthias , Kuo Chih-Hsi S. , Rajappa Senthil , Harada Guilherme , Clifford Sarah , Santucci Alison , Silva Laura , Tupper Rebecca , Oxnard Geoffrey R. , Kherani Jennifer , Drilon Alexander
Published: August 2023

Adverse events observed with combination therapy
Supplementary Figure S2 from Osimertinib and Selpercatinib Efficacy, Safety, and Resistance in a Multicenter, Prospectively Treated Cohort of EGFR-Mutant and RET Fusion-Positive Lung Cancers
Authors: Rotow Julia , Patel Jyoti D. , Hanley Matthew P. , Yu Helena , Awad Mark , Goldman Jonathan W. , Nechushtan Hovav , Scheffler Matthias , Kuo Chih-Hsi S. , Rajappa Senthil , Harada Guilherme , Clifford Sarah , Santucci Alison , Silva Laura , Tupper Rebecca , Oxnard Geoffrey R. , Kherani Jennifer , Drilon Alexander
Published: August 2023

Durable combination therapy benefit
Supplementary Figure S1 from Osimertinib and Selpercatinib Efficacy, Safety, and Resistance in a Multicenter, Prospectively Treated Cohort of EGFR-Mutant and RET Fusion-Positive Lung Cancers
Authors: Rotow Julia , Patel Jyoti D. , Hanley Matthew P. , Yu Helena , Awad Mark , Goldman Jonathan W. , Nechushtan Hovav , Scheffler Matthias , Kuo Chih-Hsi S. , Rajappa Senthil , Harada Guilherme , Clifford Sarah , Santucci Alison , Silva Laura , Tupper Rebecca , Oxnard Geoffrey R. , Kherani Jennifer , Drilon Alexander
Published: August 2023

Patient Cohort Identification
Supplementary figures 1-9 from Dual Targeting of Apoptotic and Signaling Pathways in T-Lineage Acute Lymphoblastic Leukemia
Authors: Saygin Caner , Giordano Giorgia , Shimamoto Kathryn , Eisfelder Bart , Thomas-Toth Anika , Venkataraman Girish , Ananthanarayanan Vijayalakshmi , Vincent Tiffaney L. , DuVall Adam , Patel Anand A. , Chen Yi , Tan Fenlai , Anthony Stephen P. , Chen Yu , Shen Yue , Odenike Olatoyosi , Teachey David T. , Kee Barbara L. , LaBelle James , Stock Wendy
Published: August 2023

Supplementary Figures 1-9
Table 1 from Functional Homologous Recombination Assay on FFPE Specimens of Advanced High-Grade Serous Ovarian Cancer Predicts Clinical Outcomes
Authors: Pikkusaari Sanna , Tumiati Manuela , Virtanen Anni , Oikkonen Jaana , Li Yilin , Perez-Villatoro Fernando , Muranen Taru , Salko Matilda , Huhtinen Kaisa , Kanerva Anna , Koskela Heidi , Tapper Johanna , Koivisto-Korander Riitta , Joutsiniemi Titta , Haltia Ulla-Maija , Lassus Heini , Hautaniemi Sampsa , Färkkilä Anniina , Hynninen Johanna , Hietanen Sakari , Carpén Olli , Kauppi Liisa
Published: August 2023

Clinicopathologic characteristics of patients included in the study, divided into cohorts based on sample type (chemo-naïve or IDS).
Supplementary Figure S8 from Functional Homologous Recombination Assay on FFPE Specimens of Advanced High-Grade Serous Ovarian Cancer Predicts Clinical Outcomes
Authors: Pikkusaari Sanna , Tumiati Manuela , Virtanen Anni , Oikkonen Jaana , Li Yilin , Perez-Villatoro Fernando , Muranen Taru , Salko Matilda , Huhtinen Kaisa , Kanerva Anna , Koskela Heidi , Tapper Johanna , Koivisto-Korander Riitta , Joutsiniemi Titta , Haltia Ulla-Maija , Lassus Heini , Hautaniemi Sampsa , Färkkilä Anniina , Hynninen Johanna , Hietanen Sakari , Carpén Olli , Kauppi Liisa
Published: August 2023

A. PFS-based survival curves shown separately for discovery and validation cohorts. B. Response to second-line platinum therapy. C. PFS-based survival curves excluding BRCAmut fHRD patients.
Supplementary Figure S2 from Functional Homologous Recombination Assay on FFPE Specimens of Advanced High-Grade Serous Ovarian Cancer Predicts Clinical Outcomes
Authors: Pikkusaari Sanna , Tumiati Manuela , Virtanen Anni , Oikkonen Jaana , Li Yilin , Perez-Villatoro Fernando , Muranen Taru , Salko Matilda , Huhtinen Kaisa , Kanerva Anna , Koskela Heidi , Tapper Johanna , Koivisto-Korander Riitta , Joutsiniemi Titta , Haltia Ulla-Maija , Lassus Heini , Hautaniemi Sampsa , Färkkilä Anniina , Hynninen Johanna , Hietanen Sakari , Carpén Olli , Kauppi Liisa
Published: August 2023

Image analysis workflow in ImageJ.
Supplementary Table S4 from DNA-Methylome–Based Tumor Hypoxia Classifier Identifies HPV-Negative Head and Neck Cancer Patients at Risk for Locoregional Recurrence after Primary Radiochemotherapy
Authors: Tawk Bouchra , Rein Katrin , Schwager Christian , Knoll Maximilian , Wirkner Ute , Hörner-Rieber Juliane , Liermann Jakob , Kurth Ina , Balermpas Panagiotis , Rödel Claus , Linge Annett , Löck Steffen , Lohaus Fabian , Tinhofer Ingeborg , Krause Mechtild , Stuschke Martin , Grosu Anca Ligia , Zips Daniel , Combs Stephanie E. , Belka Claus , Stenzinger Albrecht , Herold-Mende Christel , Baumann Michael , Schirmacher Peter , Debus Jürgen , Abdollahi Amir
Published: August 2023

Supplementary Table S4. Correlations with CIBERSORT immune signature expressions in the TCGA-HNSCC cohort
Figure 5 from Functional Homologous Recombination Assay on FFPE Specimens of Advanced High-Grade Serous Ovarian Cancer Predicts Clinical Outcomes
Authors: Pikkusaari Sanna , Tumiati Manuela , Virtanen Anni , Oikkonen Jaana , Li Yilin , Perez-Villatoro Fernando , Muranen Taru , Salko Matilda , Huhtinen Kaisa , Kanerva Anna , Koskela Heidi , Tapper Johanna , Koivisto-Korander Riitta , Joutsiniemi Titta , Haltia Ulla-Maija , Lassus Heini , Hautaniemi Sampsa , Färkkilä Anniina , Hynninen Johanna , Hietanen Sakari , Carpén Olli , Kauppi Liisa
Published: August 2023

Comparison between different HRD estimates. A, Hazard ratio analysis with the different HRD estimates available and PFI. Only fHR and ovaHRDScar tests produced significant results (Cox proportional hazards regression). B, Sensitivity and specificity of the different HRD tests. ovaHRDScar has the best sensitivity in detecting clinically meaningful HRD (>1y PFI), and fHR test has the best specificity in detecting clinically meaningful HR proficiency (<1y PFI).
Supplementary Table S1 from DNA-Methylome–Based Tumor Hypoxia Classifier Identifies HPV-Negative Head and Neck Cancer Patients at Risk for Locoregional Recurrence after Primary Radiochemotherapy
Authors: Tawk Bouchra , Rein Katrin , Schwager Christian , Knoll Maximilian , Wirkner Ute , Hörner-Rieber Juliane , Liermann Jakob , Kurth Ina , Balermpas Panagiotis , Rödel Claus , Linge Annett , Löck Steffen , Lohaus Fabian , Tinhofer Ingeborg , Krause Mechtild , Stuschke Martin , Grosu Anca Ligia , Zips Daniel , Combs Stephanie E. , Belka Claus , Stenzinger Albrecht , Herold-Mende Christel , Baumann Michael , Schirmacher Peter , Debus Jürgen , Abdollahi Amir
Published: August 2023

Supplementary Table S1. Multivariate Analysis for the Hypoxia-M and Brooks signature.
Supplementary Tables 1-2 from Discovery and Targeting of a Noncanonical Mechanism of Sarcoma Resistance to ADI-PEG20 Mediated by the Microenvironment
Authors: Rogers Leonard C. , Kremer Jeff C. , Brashears Caitlyn B. , Lin Zongtao , Hu Zhixian , Bastos Alliny C.S. , Baker Adriana , Fettig Nicole , Zhou Dong , Shoghi Kooresh I. , Dehner Carina A. , Chrisinger John S.A. , Bomalaski John S. , Garcia Benjamin A. , Oyama Toshinao , White Eileen P. , Van Tine Brian A.
Published: August 2023

Supplementary Tables 1-2
Supplementary Fig. 6 from Discovery and Targeting of a Noncanonical Mechanism of Sarcoma Resistance to ADI-PEG20 Mediated by the Microenvironment
Authors: Rogers Leonard C. , Kremer Jeff C. , Brashears Caitlyn B. , Lin Zongtao , Hu Zhixian , Bastos Alliny C.S. , Baker Adriana , Fettig Nicole , Zhou Dong , Shoghi Kooresh I. , Dehner Carina A. , Chrisinger John S.A. , Bomalaski John S. , Garcia Benjamin A. , Oyama Toshinao , White Eileen P. , Van Tine Brian A.
Published: August 2023

Supplemental Figure 6. RNA sequencing of tumors.
Supplementary Figure S2 from The DRD2 Antagonist Haloperidol Mediates Autophagy-Induced Ferroptosis to Increase Temozolomide Sensitivity by Promoting Endoplasmic Reticulum Stress in Glioblastoma
Authors: Shi Linyong , Chen Hanning , Chen Kunxiang , Zhong Chengzong , Song Chong , Huang Yifeng , Wang Tong , Chen Lei , Li Chiyang , Huang Annie , Qi Songtao , Li Hong , Lu Yuntao
Published: August 2023

Fig. S2. TMZ+HP Hp induces ferroptosis in GBM cells.
Supplementary Fig. 1 from Discovery and Targeting of a Noncanonical Mechanism of Sarcoma Resistance to ADI-PEG20 Mediated by the Microenvironment
Authors: Rogers Leonard C. , Kremer Jeff C. , Brashears Caitlyn B. , Lin Zongtao , Hu Zhixian , Bastos Alliny C.S. , Baker Adriana , Fettig Nicole , Zhou Dong , Shoghi Kooresh I. , Dehner Carina A. , Chrisinger John S.A. , Bomalaski John S. , Garcia Benjamin A. , Oyama Toshinao , White Eileen P. , Van Tine Brian A.
Published: August 2023

Supplemental Figure 1. In vivo imaging.
Supplementary Table S4 from Frequent Overexpression of HER3 in Brain Metastases from Breast and Lung Cancer
Authors: Tomasich Erwin , Steindl Ariane , Paiato Christina , Hatziioannou Teresa , Kleinberger Markus , Berchtold Luzia , Puhr Rainer , Hainfellner Johannes A. , Müllauer Leonhard , Widhalm Georg , Eckert Franziska , Bartsch Rupert , Heller Gerwin , Preusser Matthias , Berghoff Anna Sophie
Published: August 2023

Differentially methylated CpG sites in HER3+ vs HER3- breast cancer samples (Luminal cohort)
Supplementary Figure S3 from Frequent Overexpression of HER3 in Brain Metastases from Breast and Lung Cancer
Authors: Tomasich Erwin , Steindl Ariane , Paiato Christina , Hatziioannou Teresa , Kleinberger Markus , Berchtold Luzia , Puhr Rainer , Hainfellner Johannes A. , Müllauer Leonhard , Widhalm Georg , Eckert Franziska , Bartsch Rupert , Heller Gerwin , Preusser Matthias , Berghoff Anna Sophie
Published: August 2023

Immune cell infiltration in BM of the three subtypes of BCa: Luminal (A), HER2-positive (B) and Triple-negative breast cancer (TNBC) (C).
Supplementary Table S1 from Association of Antifolate Response Signature Status and Clinical Activity of Pemetrexed-Platinum Chemotherapy in Non–Small Cell Lung Cancer: The Piedmont Study
Authors: Eisner Joel R. , Mayhew Gregory M. , Davison James M. , Beebe Kirk D. , Shibata Yoichiro , Guo Yuelong , Farhangfar Carol , Farhangfar Farhang , Uronis Joshua M. , Conroy Jeffrey M. , Milburn Michael V. , Hayes David Neil , Mileham Kathryn F.
Published: August 2023

48 genes included in the new LUAD nearest centroid classifier and associated AF-PRS signature.
Supplementary Methods S1 from Association of Antifolate Response Signature Status and Clinical Activity of Pemetrexed-Platinum Chemotherapy in Non–Small Cell Lung Cancer: The Piedmont Study
Authors: Eisner Joel R. , Mayhew Gregory M. , Davison James M. , Beebe Kirk D. , Shibata Yoichiro , Guo Yuelong , Farhangfar Carol , Farhangfar Farhang , Uronis Joshua M. , Conroy Jeffrey M. , Milburn Michael V. , Hayes David Neil , Mileham Kathryn F.
Published: August 2023

Development of the 48-gene LUAD nearest centroid classifier
Supplementary Fig. 5 from MEK Inhibition Sensitizes Pancreatic Cancer to STING Agonism by Tumor Cell–intrinsic Amplification of Type I IFN Signaling
Authors: Ghukasyan Razmik , Liang Keke , Chau Kevin , Li Luyi , Chan Charlotte , Abt Evan R. , Le Thuc , Park Joon Y. , Wu Nanping , Premji Alykhan , Damoiseaux Robert , Luu Tony , Labora Amanda , Rashid Khalid , Link Jason M. , Radu Caius G. , Donahue Timothy R.
Published: August 2023

Supplementary Fig. 5 IL6 is not responsible for the synergistic effects of STING agonism and MEK inhibition.
Supplementary Fig. 1 from MEK Inhibition Sensitizes Pancreatic Cancer to STING Agonism by Tumor Cell–intrinsic Amplification of Type I IFN Signaling
Authors: Ghukasyan Razmik , Liang Keke , Chau Kevin , Li Luyi , Chan Charlotte , Abt Evan R. , Le Thuc , Park Joon Y. , Wu Nanping , Premji Alykhan , Damoiseaux Robert , Luu Tony , Labora Amanda , Rashid Khalid , Link Jason M. , Radu Caius G. , Donahue Timothy R.
Published: August 2023

Supplementary Fig. 1 STING agonist diABZI synergizes with MAPK inhibition in PDAC by enhancing apoptosis.
Supplementary Figure 4 from Targeting BCL2 Overcomes Resistance and Augments Response to Aurora Kinase B Inhibition by AZD2811 in Small Cell Lung Cancer
Authors: Ramkumar Kavya , Tanimoto Azusa , Della Corte Carminia M. , Stewart C. Allison , Wang Qi , Shen Li , Cardnell Robert J. , Wang Jing , Polanska Urszula M. , Andersen Courtney , Saeh Jamal , Pease J. Elizabeth , Travers Jon , Fabbri Giulia , Gay Carl M. , Urosevic Jelena , Byers Lauren A.
Published: August 2023

Supplementary Figure 4 shows the combination of AZD2811NP with venetoclax is well tolerated in mice and less efficacious in SCLC models with low BCL2 expression.
Supplementary Figure 3 from Targeting BCL2 Overcomes Resistance and Augments Response to Aurora Kinase B Inhibition by AZD2811 in Small Cell Lung Cancer
Authors: Ramkumar Kavya , Tanimoto Azusa , Della Corte Carminia M. , Stewart C. Allison , Wang Qi , Shen Li , Cardnell Robert J. , Wang Jing , Polanska Urszula M. , Andersen Courtney , Saeh Jamal , Pease J. Elizabeth , Travers Jon , Fabbri Giulia , Gay Carl M. , Urosevic Jelena , Byers Lauren A.
Published: August 2023

Supplementary Figure 3 shows the combination of AZD2811 and BCL2 inhibitor enhances apoptosis and cell death.
Supplementary Figure 2 from Targeting BCL2 Overcomes Resistance and Augments Response to Aurora Kinase B Inhibition by AZD2811 in Small Cell Lung Cancer
Authors: Ramkumar Kavya , Tanimoto Azusa , Della Corte Carminia M. , Stewart C. Allison , Wang Qi , Shen Li , Cardnell Robert J. , Wang Jing , Polanska Urszula M. , Andersen Courtney , Saeh Jamal , Pease J. Elizabeth , Travers Jon , Fabbri Giulia , Gay Carl M. , Urosevic Jelena , Byers Lauren A.
Published: August 2023

Supplementary Figure 2 shows polyploidy and apoptosis are inhibited by high BCL2 levels
Supplementary Data 1 from Targeting BCL2 Overcomes Resistance and Augments Response to Aurora Kinase B Inhibition by AZD2811 in Small Cell Lung Cancer
Authors: Ramkumar Kavya , Tanimoto Azusa , Della Corte Carminia M. , Stewart C. Allison , Wang Qi , Shen Li , Cardnell Robert J. , Wang Jing , Polanska Urszula M. , Andersen Courtney , Saeh Jamal , Pease J. Elizabeth , Travers Jon , Fabbri Giulia , Gay Carl M. , Urosevic Jelena , Byers Lauren A.
Published: August 2023

Supplementary table shows AZD2811 sensitivity, transcriptomic and proteomic profiles of SCLC cell lines
Supplementary Data 2 from Clinical Activity of Combined Telomerase Vaccination and Pembrolizumab in Advanced Melanoma: Results from a Phase I Trial
Authors: Ellingsen Espen B. , O'Day Steven , Mezheyeuski Artur , Gromadka Agnieszka , Clancy Trevor , Kristedja Timothy S. , Milhem Mohammed , Zakharia Yousef
Published: August 2023

Figure S2
Supplementary Data 2 from Clinical Activity of Combined Telomerase Vaccination and Pembrolizumab in Advanced Melanoma: Results from a Phase I Trial
Authors: Ellingsen Espen B. , O'Day Steven , Mezheyeuski Artur , Gromadka Agnieszka , Clancy Trevor , Kristedja Timothy S. , Milhem Mohammed , Zakharia Yousef
Published: August 2023

Table S2
Supplementary Table S1 from Evaluation of Somatic Mutations in Urine Samples as a Noninvasive Method for the Detection and Molecular Classification of Endometrial Cancer
Authors: Costas Laura , Onieva Irene , Pelegrina Beatriz , Marin Fátima , Carmona Álvaro , López-Querol Marta , Frias-Gomez Jon , Peremiquel-Trillas Paula , Martínez José Manuel , Dorca Eduard , Brunet Joan , Pineda Marta , Ponce Jordi , Matias-Guiu Xavier , de Sanjosé Silvia , Bosch Francesc Xavier , Alemany Laia , Paytubi Sonia
Published: August 2023

Descriptive characteristics of participants
Supplementary Figure 1 from Phase I Trial of the Multi-kinase Inhibitor Cabozantinib, a CYP3A4 Substrate, plus CYP3A4-Interacting Antiretroviral Therapy in People Living with HIV and Cancer (AMC-087)
Authors: Haigentz Missak , Lee Jeannette Y. , Chiao Elizabeth Y. , Aboulafia David M. , Ratner Lee , Ambinder Richard F. , Baiocchi Robert A. , Mitsuyasu Ronald T. , Wachsman William , Sparano Joseph A. , Rudek Michelle A.
Published: August 2023

Supplementary Figure 1. Average and standard deviation concentration–time profile of cabozantinib at steady-state on a semi-log plot for stratum A (A), stratum B (B), and stratum C (C). Doses are noted in the figures.
Data from Spatial Immunoprofiling of Adenoid Cystic Carcinoma Reveals B7-H4 Is a Therapeutic Target for Aggressive Tumors
Authors: Sousa Luana Guimaraes , McGrail Daniel J. , Lazar Neto Felippe , Li Kaiyi , Marques-Piubelli Mario L. , Ferri-Borgogno Sammy , Dai Hui , Mitani Yoshitsugu , Spardy Burr Nicole , Cooper Zachary A. , Kinneer Krista , Cortez Maria Angelica , Lin Shiaw-Yih , Bell Diana , El Naggar Adel , Burks Jared , Ferrarotto Renata
Published: August 2023

AbstractPurpose:
Adenoid cystic carcinoma (ACC) is a heterogeneous malignancy, and no effective systemic therapy exists for metastatic disease. We previously described two prognostic ACC molecular subtypes with distinct therapeutic vulnerabilities, ACC-I and ACC-II. In this study, we explored the ACC tumor microenvironment (TME) using RNA-sequencing and spatial biology to identify potential therapeutic targets.
Experimental Design:
Tumor samples from 62 ACC patients with available RNA-sequencing data that had been collected as part of previous studies were stained with a panel of 28 validated metal-tagged antibodies. Imaging mass cytometry (IMC) was performed using the Fluidigm Helios CyTOF instrument and analyzed with Visiopharm software. The B7-H4 antibody–drug conjugate AZD8205 was tested in ACC patient-derived xenografts (PDX).
Results:
RNA deconvolution revealed that most ACCs are immunologically “cold,” with approximately 30% being “hot.” ACC-I tumors with a poor prognosis harbored a higher density of immune cells; however, spatial analysis by IMC revealed that ACC-I immune cells were significantly restricted to the stroma, characterizing an immune-excluded TME. ACC-I tumors overexpressed the immune checkpoint B7-H4, and the degree of immune exclusion was directly correlated with B7-H4 expression levels, an independent predictor of poor survival. Two ACC-I/B7-H4-high PDXs obtained 90% complete responses to a single dose of AZD8205, but none were observed with isotype-conjugated payload or in an ACC-II/B7-H4 low PDX.
Conclusions:
Spatial analysis revealed that ACC subtypes have distinct TMEs, with enrichment of ACC-I immune cells that are restricted to the stroma. B7-H4 is highly expressed in poor-prognosis ACC-I subtype and is a potential therapeutic target.
Data from Genetic Alterations Detected by Circulating Tumor DNA in HER2-Low Metastatic Breast Cancer
Authors: Hensing Whitney L. , Gerratana Lorenzo , Clifton Katherine , Medford Arielle J. , Velimirovic Marko , Shah Ami N. , D'Amico Paolo , Reduzzi Carolina , Zhang Qiang , Dai Charles S. , Denault Elyssa N. , Bagegni Nusayba A. , Opyrchal Mateusz , Ademuyiwa Foluso O. , Bose Ron , Behdad Amir , Ma Cynthia X. , Bardia Aditya , Cristofanilli Massimo , Davis Andrew A.
Published: August 2023

AbstractPurpose:
About 50% of breast cancers are defined as HER2-low and may benefit from HER2-directed antibody–drug conjugates. While tissue sequencing has evaluated potential differences in genomic profiles for patients with HER2-low breast cancer, genetic alterations in circulating tumor DNA (ctDNA) have not been well described.
Experimental Design:
We retrospectively analyzed 749 patients with metastatic breast cancer (MBC) and ctDNA evaluation by Guardant360 from three academic medical centers. Tumors were classified as HER2-low, HER2-0 (IHC 0) or HER2-positive. Single-nucleotide variants, copy-number variants, and oncogenic pathways were compared across the spectrum of HER2 expression. Overall survival (OS) was evaluated by HER2 status and according to oncogenic pathways.
Results:
Patients with HER2-low had higher rates of PIK3CA mutations [relative risk ratio (RRR), 1.57; P = 0.024] compared with HER2-0 MBC. There were no differences in ERBB2 alterations or oncogenic pathways between HER2-low and HER2-0 MBC. Patients with HER2-positive MBC had more ERBB2 alterations (RRR, 12.43; P = 0.002 for amplification; RRR, 3.22; P = 0.047 for mutations, in the hormone receptor–positive cohort), fewer ERS1 mutations (RRR, 0.458; P = 0.029), and fewer ER pathway alterations (RRR, 0.321; P < 0.001). There was no difference in OS for HER2-low and HER2-0 MBC [HR, 1.01; 95% confidence interval (CI), 0.79–1.29], while OS was improved in HER2-positive MBC (HR, 0.32; 95% CI, 0.21–0.49; P < 0.001).
Conclusions:
We observed a higher rate of PIK3CA mutations, but no significant difference in ERBB2 alterations, oncogenic pathways, or prognosis, between patients with HER2-low and HER2-0 MBC. If validated, our findings support the conclusion that HER2-low MBC does not represent a unique biological subtype.
Data from Evaluation of somatic mutations in urine samples as a non-invasive method for the detection and molecular classification of endometrial cancer
Authors: Costas Laura , Onieva Irene , Pelegrina Beatriz , Marin Fátima , Carmona Alvaro , López-Querol Marta , Frias-Gomez Jon , Peremiquel-Trillas Paula , Martínez José Manuel , Dorca Eduard , Brunet Joan , Pineda Marta , Ponce Jordi , Matías-Guiu Xavier , de Sanjosé Silvia , Bosch Francesc Xavier , Alemany Laia , Paytubi Sonia
Published: August 2023

Abstract
Purpose: Current diagnostic methods for endometrial cancer lack specificity, leading to many women undergoing invasive procedures. The aim of this study was to evaluate somatic mutations in urine to accurately discriminate endometrial cancer patients from controls. Experimental Design: Overall, 72 samples were analyzed using next-generation sequencing with molecular identifiers targeting 47 genes. We evaluated urine supernatant samples from women with endometrial cancer (n=19) and age-matched controls (n=20). Cell pellets from urine and plasma samples from seven cases were sequenced; further, we also evaluated paired tumor samples from all cases. Finally, immunohistochemical markers for molecular profiling were evaluated in all tumor samples. Results: Overall, we were able to identify mutations in DNA from urine supernatant samples in 100% of endometrial cancers. In contrast, only one control (5%) showed variants at a variant allele frequency (VAF)≥2% in the urine supernatant samples. The molecular classification obtained by using tumor samples and urine samples showed good agreement. Analyses in paired samples revealed a higher number of mutations and VAFs in urine supernatants than in urine cell pellets and blood samples. Conclusions: Evaluation of somatic mutations using urine samples may offer a user-friendly and reliable tool for endometrial cancer detection and molecular classification. The diagnostic performance for endometrial cancer detection was very high, and cases could be molecularly classified using these noninvasive and self-collected samples. Additional multi-center evaluations using larger sample sizes are needed to validate the results and understand the potential of urine samples for the early detection and prognosis of endometrial cancer.
Data from Phase I trial of the multi-kinase inhibitor cabozantinib, a CYP3A4 substrate, plus CYP3A4 interacting antiretroviral therapy in people living HIV and cancer (AMC087)
Authors: Haigentz Missak , Lee Jeannette Y. , Chiao Elizabeth Y. , Aboulafia David M. , Ratner Lee , Ambinder Richard F. , Baiocchi Robert A. , Mitsuyasu Ronald T. , Wachsman William , Sparano Joseph A. , Rudek Michelle A.
Published: August 2023

Abstract
Purpose: To evaluate the safety, pharmacokinetics, and pharmacodynamic effects of cabozantinib, a CYP3A4 substrate, in people living with HIV (PLWH) and cancer receiving antiretrovirals (ARVs). Experimental Design: Patients received a reduced dose of cabozantinib (20 mg PO daily) with strong CYP3A4 inhibitors (ARV ritonavir or non-ARV cobicistat, stratum A), or a standard 60 mg dose with ARVs that are CYP3A4 inducers (efavirenz or etravirine, stratum B) or non-interacting ARVs (stratum C). Initial dose escalation in stratum A and stratum B was performed based on tolerability. Results: 36 patients received cabozantinib plus ARVs, including 20 in stratum A, 9 in B, and 7 in C. The recommended initial cabozantinib dose for stratum A, B, and C were 20, 60, and 60 mg, respectively. Doses of 40 or 60 mg plus CYP3A4 inhibitors in stratum A and 100 mg plus CYP3A4 inducers in stratum B were associated with excessive toxicity, whereas 60 mg with non-interacting ARVs was not. The steady state minimal concentrations were lower at 20 mg in stratum A or 60 mg in stratum B compared to 60 mg in stratum C, while total exposure was only lower in 60 mg in stratum B compared to 60 mg in stratum C. Activity was observed in Kaposi sarcoma and an AXL-amplified sarcoma. Conclusions: Cabozantinib as a single agent should be initiated at 20 mg daily and 60 mg daily when taken concurrently with ARVs that are strong CYP3A4 inhibitors and inducers, respectively, with consideration for subsequent escalation per current cabozantinib guidelines.
Data from Phase I Trial of the Multi-kinase Inhibitor Cabozantinib, a CYP3A4 Substrate, plus CYP3A4-Interacting Antiretroviral Therapy in People Living with HIV and Cancer (AMC-087)
Authors: Haigentz Missak , Lee Jeannette Y. , Chiao Elizabeth Y. , Aboulafia David M. , Ratner Lee , Ambinder Richard F. , Baiocchi Robert A. , Mitsuyasu Ronald T. , Wachsman William , Sparano Joseph A. , Rudek Michelle A.
Published: August 2023

AbstractPurpose:
To evaluate the safety, pharmacokinetics, and pharmacodynamic effects of cabozantinib, a CYP3A4 substrate, in people living with human immunodeficiency virus and cancer receiving antiretrovirals (ARV).
Patients and Methods:
Patients received a reduced dose of cabozantinib (20 mg orally daily) with strong CYP3A4 inhibitors (ARV ritonavir or non-ARV cobicistat, stratum A), or a standard 60 mg dose with ARVs that are CYP3A4 inducers (efavirenz or etravirine, stratum B) or noninteracting ARVs (stratum C). Initial dose escalation in stratum A and stratum B was performed on the basis of tolerability.
Results:
36 patients received cabozantinib plus ARVs, including 20 in stratum A, 9 in B, and 7 in C. The recommended initial cabozantinib doses for stratum A, B, and C were 20, 60, and 60 mg, respectively. Doses of 40 or 60 mg plus CYP3A4 inhibitors in stratum A and 100 mg plus CYP3A4 inducers in stratum B were associated with excessive toxicity, whereas 60 mg with noninteracting ARVs was not. The steady state minimal concentrations were lower at 20 mg in stratum A or 60 mg in stratum B compared with 60 mg in stratum C, while total exposure was only lower in 60 mg in stratum B compared with 60 mg in stratum C. Activity was observed in Kaposi sarcoma and an AXL-amplified sarcoma.
Conclusions:
Cabozantinib as a single agent should be initiated at 20 mg daily and 60 mg daily when taken concurrently with ARVs that are strong CYP3A4 inhibitors and inducers, respectively, with consideration for subsequent escalation per current cabozantinib guidelines.
Facts and Hopes on RAS Inhibitors and Cancer Immunotherapy
Authors: Boumelha Jesse , Molina-Arcas Miriam , Downward Julian
Published: August 2023

Although the past decade has seen great strides in the development of immunotherapies that reactivate the immune system against tumors, there have also been major advances in the discovery of drugs blocking oncogenic drivers of cancer growth. However, there has been very little progress in combining immunotherapies with drugs that target oncogenic driver pathways. Some of the most important oncogenes in human cancer encode RAS family proteins, although these have proven challenging to target. Recently drugs have been approved that inhibit a specific mutant form of KRAS: G12C. These have improved the treatment of patients with lung cancer harboring this mutation, but development of acquired drug resistance after initial responses has limited the impact on overall survival. Because of the immunosuppressive nature of the signaling network controlled by oncogenic KRAS, targeted KRAS G12C inhibition can indirectly affect antitumor immunity, and does so without compromising the critical role of normal RAS proteins in immune cells. This serves as a rationale for combination with immune checkpoint blockade, which can provide additional combinatorial therapeutic benefit in some preclinical cancer models. However, in clinical trials, combination of KRAS G12C inhibitors with PD-(L)1 blockade has yet to show improved outcome, in part due to treatment toxicities. A greater understanding of how oncogenic KRAS drives immune evasion and how mutant-specific KRAS inhibition impacts the tumor microenvironment can lead to novel approaches to combining RAS inhibition with immunotherapies.
On the Precipice of a “Rituximab-Like” Era for T-Cell Lymphomas?
Authors: Varma Gaurav , Diefenbach Catherine S.
Published: August 2023

To date, mAbs have had limited success in improving outcomes for patients with T-cell lymphomas. Preclinical data suggest that anti–T-cell receptor Vβ-segment mAbs are a novel therapeutic strategy for patients with T-cell lymphomas that avoid several limitations of current therapies.

See related article by Lucero et al., p. 4230
Table S5 from Clinical benefit of autologous stem cell transplantation for multiple myeloma patients achieving undetectable minimal residual disease after induction treatment
Authors: Liu Jiahui , Yan Wenqiang , Fan Huishou , Xu Jingyu , Li Lingna , Du Chenxing , Mao Xuehan , Yan Yuting , Xu Yan , Sui Weiwei , Deng Shuhui , Yi Shuhua , Anderson Kenneth C. , Qiu Lugui , Zou Dehui , An Gang
Published: August 2023

Patient and Treatment Characteristics in ASCT cohort: Sustained MRD-negative vs. Sustained MRD-positive
Table S4 from Clinical benefit of autologous stem cell transplantation for multiple myeloma patients achieving undetectable minimal residual disease after induction treatment
Authors: Liu Jiahui , Yan Wenqiang , Fan Huishou , Xu Jingyu , Li Lingna , Du Chenxing , Mao Xuehan , Yan Yuting , Xu Yan , Sui Weiwei , Deng Shuhui , Yi Shuhua , Anderson Kenneth C. , Qiu Lugui , Zou Dehui , An Gang
Published: August 2023

Univariate and multivariate analyses of MRD negativity duration
Supplementary Figure 8 from Kinase Inhibitor Pulldown Assay Identifies a Chemotherapy Response Signature in Triple-negative Breast Cancer Based on Purine-binding Proteins
Authors: Wang Junkai , Saltzman Alexander B. , Jaehnig Eric J. , Lei Jonathan T. , Malovannaya Anna , Holt Matthew V. , Young Meggie N. , Rimawi Mothaffar F. , Ademuyiwa Foluso O. , Anurag Meenakshi , Kim Beom-Jun , Ellis Matthew J.
Published: August 2023

Supplementary Figure 8
FIGURE 3 from Kinase Inhibitor Pulldown Assay Identifies a Chemotherapy Response Signature in Triple-negative Breast Cancer Based on Purine-binding Proteins
Authors: Wang Junkai , Saltzman Alexander B. , Jaehnig Eric J. , Lei Jonathan T. , Malovannaya Anna , Holt Matthew V. , Young Meggie N. , Rimawi Mothaffar F. , Ademuyiwa Foluso O. , Anurag Meenakshi , Kim Beom-Jun , Ellis Matthew J.
Published: August 2023

GSEA of the PBP signature-correlated genes. A, Bar plot shows the enriched Hallmark gene sets (FDR < 0.05) from GSEA of the KIPA-based PBP signature score-correlated genes at the protein levels. GSEA input was a ranked list of signed −log10P-values from Pearson correlation between the KIPA-based PBP signature score and all the genes measured by the global proteomics in the CPTAC-TNBC dataset. Pathways with positive NES (normalized enrichment score) were positively correlated with the KIPA-based PBP signature score, while pathways with negative NES were negatively correlated. B, Enrichment plots for INTERFERON_GAMMA_RESPONSE Hallmark pathway at the protein levels. C, Bar plot shows the enriched Hallmark gene sets (FDR < 0.05) from GSEA of the KIPA-based PBP signature score-correlated genes at the mRNA levels. GSEA input was a ranked list of signed −log10P-values from Pearson correlation between the KIPA-based PBP signature score and all the genes measured by the RNA-seq. D, Enrichment plots for INTERFERON_GAMMA_RESPONSE Hallmark pathway at the mRNA levels.
Data from Clinical Benefit of Autologous Stem Cell Transplantation for Patients with Multiple Myeloma Achieving Undetectable Minimal Residual Disease after Induction Treatment
Authors: Liu Jiahui , Yan Wenqiang , Fan Huishou , Xu Jingyu , Li Lingna , Du Chenxing , Mao Xuehan , Yan Yuting , Xu Yan , Sui Weiwei , Deng Shuhui , Yi Shuhua , Anderson Kenneth C. , Qiu Lugui , Zou Dehui , An Gang
Published: August 2023

Attaining undetectable minimal residual disease (MRD) is the current therapeutic goal for multiple myeloma. But there is a current lack of data regarding the clinical benefit of autologous stem cell transplantation (ASCT) for patients with myeloma achieving early MRD-negative status after induction treatment, in addition to the interaction of longitudinal MRD status with ASCT. The current study included 407 patients with transplant-eligible multiple myeloma with available MRD status from the National Longitudinal Cohort of Hematological Diseases in China (NCT04645199), of whom 147 (34.4%) achieved early undetectable MRD and 182 (44.7%) received ASCT. Early MRD-negative status was associated with a lower risk of disease progression [HR = 0.447; 95% confidence interval (CI), 0.333–0.600; P < 0.001] and death (HR = 0.473; 95% CI, 0.320–0.700; P < 0.001). Of note, patients who achieved undetectable MRD early still benefitted from ASCT, with a remarkable improvement in the median MRD-negative duration (33.5–58.0 months, P < 0.001), progression-free survival (PFS; 46.0–88.3 months, P < 0.001), and overall survival (OS; 76.4 months to not reached, P = 0.003). These clinical benefits were more pronounced in patients with aggressive features (high-risk cytogenetic abnormalities or high tumor burden) compared with standard-risk patients. Similar results were observed in patients with detectable MRD after induction treatment. In addition, we identified four MRD-status transformation patterns following ASCT, which were strongly correlated with diverse survival outcomes (P < 0.001). Our study revealed the enhanced clinical significance of ASCT in patients with transplant-eligible myeloma, regardless of early MRD status, particularly for high-risk patients. Subsequent prospective trials are essential to validate these observations.
Significance:
Achieving and maintaining undetectable MRD is the current treatment goal for multiple myeloma. Our results emphasized the remarkable clinical benefit of ASCT on MRD-negative duration, PFS, and OS in patients with multiple myeloma regardless of early MRD status. These favorable impacts were more evident in patients with aggressive features. Importantly, dynamic MRD monitoring among ASCT could facilitate personalized stratification of therapeutic approaches.
A Randomized, Double-Blind, Placebo-Controlled, Multicenter, 16-Week Trial to Evaluate the Efficacy and Safety of FB-401 in Children, Adolescents, and Adult Subjects (Ages 2 Years and Older) with Mild-to-Moderate Atopic Dermatitis
Authors: Jacobson Michael E. , Myles Ian A. , Paller Amy S. , Eichenfield Lawrence F. , Simpson Eric L.
Published: August 2023

Background: Atopic dermatitis is a common chronic, relapsing, and remitting inflammatory skin disorder associated with cutaneous dysbiosis. Current treatment options often fail to adequately control the disease and have unfavorable safety profiles. There is a need for new options that address these treatment shortcomings. Objective: The aim of the study was to evaluate the efficacy, safety, and tolerability of FB-401, a live therapeutic product of 3 strains of Roseomonas mucosa, compared to matching placebo applied topically 3 times per week to participants ages ≥2 years of age with mild-to-moderate atopic dermatitis. Methods: A randomized, double-blind, placebo-controlled, parallel-group study was conducted. The primary outcome was the proportion of participants with 50% improvement in Eczema Area and Severity Index score from baseline at week 16. 154 subjects aged 2 or older with a clinical diagnosis of atopic dermatitis as defined by Hanifin and Rajka criteria with mild or moderate severity were randomized 1:1 via interactive web response system to FB-401 or placebo. Results: The proportion of subjects who achieved the primary outcome was similar between both treatment groups, with no significant treatment group differences observed at any post-baseline visit. The number of treatment-emergent adverse events and the number of subjects with at least one were similar across treatment groups. One serious adverse event not related to treatment was reported. No treatment-emergent adverse events led to treatment discontinuation or study discontinuation. Conclusions: FB-401 showed an acceptable safety profile but failed to prove superior to placebo in treating children and adults with mild-to-moderate atopic dermatitis.
Discrepancies in Vessel Density and Blood Flow Distribution in Different Areas of the Iris among Pediatric Type 1 Diabetes Mellitus and Adult Type 2 Diabetes Mellitus Patients
Authors: Cui Lipu , Xiao Ying , Qian Yu , Lin Qiurong , Xiang Zhaoyu , Chen Zhangling , Sun Jiaqi , Qin Xinran , Yang Chenhao , Zou Haidong
Published: August 2023

Introduction: Diabetes mellitus may compromise the vasculature of the iris, thereby leading to severe vision-threatening complications. This study aimed to investigate differences in iris blood flow indices between pediatric type 1 diabetes mellitus (T1DM) patients and adult type 2 diabetes mellitus (T2DM) patients. Methods: This was a cross-sectional study. Pediatric T1DM patients and healthy children were members of the Shanghai Children and Adolescent Diabetes Eye (SCADE) cohort who visited Shanghai Eye Hospital in February 2022. The adult T2DM patients and healthy adults were patients who visited Shanghai General Hospital from October 2021 to January 2022. Iris OCTA was acquired through a Cirrus HD-OCT 5000 angiography system (Carl Zeiss Meditec, Inc.). A unique iris OCTA quantification method was used, and the vessel area density (VAD) and vessel skeleton density (VSD) were obtained. The area from the pupillary margin to the corneoscleral limbus was taken as the whole iris blood flow index, and the inner third near the pupillary margin of the whole iris was taken as the pupillary margin blood flow index. Results: This study enrolled 34 pediatric T1DM patients, 34 age-matched healthy children, 34 adult T2DM patients, and 34 age-matched healthy adults. The whole iris and pupillary margin VAD and VSD of the pediatric T1DM patients were not different from those of healthy children. The whole iris VAD and VSD of the adult T2DM patients were lower than those of healthy adults, and the pupillary margin VAD and VSD were the same in these two groups. Compared with adult T2DM patients, pediatric T1DM patients had higher whole iris VAD and VSD and lower pupillary margin VAD and VSD values, all with statistical significance. Among diabetic patients, age, BMI, and glycated hemoglobin level were negative independent influencing factors for whole iris VAD and VSD, and age was a positive influencing factor for pupillary margin VAD and VSD. Conclusion: There are diverse alterations in iris vessel density and blood flow distribution between pediatric T1DM patients and adult T2DM patients.
Intravitreal Triamcinolone Acetonide for Diabetic Macular Edema and Macular Edema Secondary to Retinal Vein Occlusion: A Meta-Analysis
Authors: Mihalache Andrew , Hatamnejad Amin , Patil Nikhil S. , Popovic Marko M. , Kertes Peter J. , Cruz-Pimentel Miguel , Muni Rajeev H.
Published: August 2023

Background: The comparative safety and efficacy of different doses of intravitreal triamcinolone acetonide (IVTA) for diabetic macular edema (DME) and macular edema (ME) secondary to retinal vein occlusion (RVO) is unclear. Objectives: This meta-analysis aimed to compare the safety and efficacy of different doses of IVTA in this setting. Methods: A systematic literature search for randomized clinical trials (RCTs) was conducted on Cochrane Library, Ovid MEDLINE, and EMBASE from January 2005 to May 2022. Studies that reported on patients with DME or ME secondary to RVO that received treatment with different doses of IVTA were included. A random-effects meta-analysis was performed. Cochrane’s Risk of Bias Tool 2 was used to assess the risk of bias, and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) guidelines were used to assess certainty of evidence. Results: Five RCTs reporting on 1,041 eyes at baseline were included in this meta-analysis. In eyes with ME secondary to RVO, high-dose (4 mg) IVTA achieved a significantly better change in best-corrected visual acuity (WMD = −4.75 ETDRS letters, 95% CI = [−7.73, −1.78], p = 0.002) and reduction in retinal thickness (WMD = −93.02 μm, 95% CI = [−153.23, −32.82], p = 0.002) at months 4–6 compared to low-dose (1–2 mg) IVTA. However, high-dose IVTA had a higher risk of intraocular pressure-related adverse events (RR = 2.99, 95% CI = [1.05, 8.50], p = 0.04) and cataract surgery (RR = 5.67, 95% CI = [3.09, 10.41], p < 0.00001) than low-dose IVTA in eyes with ME secondary to RVO. These efficacy and safety differences in high-dose and low-dose IVTA were not observed in DME eyes. Conclusions: The RCT evidence in this setting is limited. High-dose IVTA achieved greater improvements in visual acuity and reductions in retinal thickness than low-dose IVTA at months 4–6. However, high-dose IVTA had a less favorable safety profile than low-dose IVTA. The significance of these outcomes was based on patients with ME secondary to RVO, but not DME.
Origin of Residual Tumor Masses in BRCA1/2-Driven Ovarian Carcinomas Treated by Neoadjuvant Chemotherapy: Selection of Preexisting BRCA1/2-Proficient Tumor Cells but Not the Gain of Second ORF-Restoring Mutation
Authors: Sokolenko Anna , Preobrazhenskaya Elena , Marchetti Claudia , Piermattei Alessia , Zagrebin Fedor , Kuligina Ekatherina , Gorodnova Tatiana , Pavone Matteo , Ivantsov Alexandr , Bizin Ilya , Scambia Giovanni , Berlev Igor , Fagotti Anna , Imyanitov Evgeny
Published: August 2023

Introduction: Tubo-ovarian carcinomas (OCs) are highly sensitive to platinum-based neoadjuvant chemotherapy (NACT) but almost never demonstrate complete pathologic response. Methods: We analyzed paired primary and residual tumor tissues from 30 patients with hereditary BRCA1/2-driven OCs (BRCA1: 17; BRCA2: 13), who were treated by carboplatin/paclitaxel NACT (median number of cycles: 3, range: 3–6). BRCA1/2 and TP53 genes were analyzed by the next-generation sequencing. The ratio between TP53 mutation-specific versus wild-type reads was considered to monitor the proportion of tumor and non-tumor cells in the tissue sample, and the ratio between BRCA1/2-mutated and wild-type reads was used to estimate the presence of cells with the loss or retention of heterozygosity (LOH or ROH, respectively). Results: All 30 OCs had BRCA1/2 LOH in primary tumor and carried somatic TP53 mutation. Twenty-eight OCs had sufficient tumor cell cellularity in the post-NACT tissue to evaluate the ratio between mutated and wild-type BRCA1/2 alleles. Five (18%) out of 28 informative tumor pairs showed transition from LOH to ROH during NACT presumably affecting all or the vast majority of residual tumor cells. There were no signals of the emergence of a second open reading frame-restoring BRCA1/2 mutation. Conclusion: Chemonaive BRCA1/2-driven carcinomas may contain a fraction of tumor cells with preserved BRCA1/2 heterozygosity. NACT can cause a selection of pre-existing BRCA1/2-proficient tumor cells, without gaining secondary reversal BRCA1/2 mutations.
Glomeruli Count and Arterial Injury in Real-Time Ultrasound-Guided Needle Kidney Biopsy Specimens: Adequacy of Three Approaches for Pig Kidneys
Authors: Nishino Tomohiko , Hirano Sakurako , Takemura Shin , Tomori Shinya , Ono Sayaka , Takahashi Kazuhiro , Mimaki Masakazu
Published: August 2023

Introduction: Real-time ultrasound-guided percutaneous kidney biopsy is essential for diagnosis and treatment planning; nonetheless, the optimal puncture approach has yet to be established. In vivo, performing different approaches on the same patient at once is not possible. This study aimed to determine the impact of different approaches on the number of obtained glomeruli and their potential to cause arterial injury using pig kidneys, which are similar to humans. Methods: A total of 120 pig kidneys (60 right-sided kidneys and 60 left-sided kidneys) for research were obtained from a slaughterhouse. The specimens were collected from the lower pole on the sagittal plane of the kidney using three different approaches on the same kidney: caudocranial approach, caudal to cranial; craniocaudal approach, cranial to caudal; and vertical approach, through the surface cortex. Five blinded pediatric nephrologists assessed the number of glomeruli and arterial injuries. Results: Overall, 360 specimens were collected from the kidneys through biopsy using a 16-gauge needle (mean vertical kidney length, 11.2 ± 0.7 cm; mean depth, 3.47 ± 0.23 cm). No significant difference in the incidence of arterial injury was observed between the three approaches (caudocranial vs. craniocaudal vs. vertical approaches: 78% vs. 87% vs. 87%, p = 0.14). In contrast, the vertical approach retrieved significantly more glomeruli than the caudocranial and craniocaudal approaches (caudocranial approach: 7.5 ± 2.8, craniocaudal approach: 7.8 ± 2.7, and vertical approach: 8.9 ± 3.3, p < 0.001). Conclusions: Considering its efficacy and safety profile, the vertical approach may be preferred, as more glomeruli can be obtained without increasing the incidence of arterial injury. Although the results cannot be directly extrapolated to humans due to the differences between species, they still offer important insights into the characteristics of each approach.