bluuebunny/crossref_metadata_2025 huggingface dataset:
Supplementary Table S6 from Zoledronic Acid Add-on Therapy for Standard-Risk Ewing Sarcoma Patients in the Ewing 2008R1 Trial
Authors: Koch Raphael , Haveman Lianne , Ladenstein Ruth , Brichard Benedicte , Jürgens Heribert , Cyprova Sona , van den Berg Henk , Hassenpflug Wolf , Raciborska Anna , Ek Torben , Baumhoer Daniel , Egerer Gerlinde , Kager Leo , Renard Marleen , Hauser Peter , Burdach Stefan , Bovee Judith V.M.G. , Hong Angela M. , Reichardt Peter , Kruseova Jarmila , Streitbürger Arne , Kühne Thomas , Kessler Torsten , Bernkopf Marie , Butterfaß-Bahloul Trude , Dhooge Catharina , Bauer Sebastian , Kiss János , Paulussen Michael , Bonar Fiona , Ranft Andreas , Timmermann Beate , Rascon Jelena , Vieth Volker , Kanerva Jukka , Faldum Andreas , Hartmann Wolfgang , Hjorth Lars , Bhadri Vivek A. , Metzler Markus , Gelderblom Hans , Dirksen Uta
Published: December 2023

Distribution of maximum acute toxicity grade over the maintenance treatment for each type of toxicity, according to treatment group (safety data set, as-treated)
Supplementary Table S4 from Zoledronic Acid Add-on Therapy for Standard-Risk Ewing Sarcoma Patients in the Ewing 2008R1 Trial
Authors: Koch Raphael , Haveman Lianne , Ladenstein Ruth , Brichard Benedicte , Jürgens Heribert , Cyprova Sona , van den Berg Henk , Hassenpflug Wolf , Raciborska Anna , Ek Torben , Baumhoer Daniel , Egerer Gerlinde , Kager Leo , Renard Marleen , Hauser Peter , Burdach Stefan , Bovee Judith V.M.G. , Hong Angela M. , Reichardt Peter , Kruseova Jarmila , Streitbürger Arne , Kühne Thomas , Kessler Torsten , Bernkopf Marie , Butterfaß-Bahloul Trude , Dhooge Catharina , Bauer Sebastian , Kiss János , Paulussen Michael , Bonar Fiona , Ranft Andreas , Timmermann Beate , Rascon Jelena , Vieth Volker , Kanerva Jukka , Faldum Andreas , Hartmann Wolfgang , Hjorth Lars , Bhadri Vivek A. , Metzler Markus , Gelderblom Hans , Dirksen Uta
Published: December 2023

Cause-specific analysis of the treatment effect on the different component of the event-free survival since randomization.
Supplementary Figure S3 from Genomic Tumor Correlates of Clinical Outcomes Following Organ-Sparing Chemoradiation Therapy for Bladder Cancer
Authors: Kamran Sophia C. , Zhou Yuzhen , Otani Keisuke , Drumm Michael , Otani Yukako , Wu Shulin , Wu Chin-Lee , Feldman Adam S. , Wszolek Matthew , Lee Richard J. , Saylor Philip J. , Lennerz Jochen , Van Allen Eliezer , Willers Henning , Hong Theodore S. , Liu Yang , Davicioni Elai , Gibb Ewan A. , Shipley William U. , Mouw Kent W. , Efstathiou Jason A. , Miyamoto David T.
Published: December 2023

Mutational signatures identified in TMT cohort.
Supplementary Figure S2 from Genomic Tumor Correlates of Clinical Outcomes Following Organ-Sparing Chemoradiation Therapy for Bladder Cancer
Authors: Kamran Sophia C. , Zhou Yuzhen , Otani Keisuke , Drumm Michael , Otani Yukako , Wu Shulin , Wu Chin-Lee , Feldman Adam S. , Wszolek Matthew , Lee Richard J. , Saylor Philip J. , Lennerz Jochen , Van Allen Eliezer , Willers Henning , Hong Theodore S. , Liu Yang , Davicioni Elai , Gibb Ewan A. , Shipley William U. , Mouw Kent W. , Efstathiou Jason A. , Miyamoto David T.
Published: December 2023

Comutation plot of MIBC TCGA genes.
Supplementary Table S1 from Zoledronic Acid Add-on Therapy for Standard-Risk Ewing Sarcoma Patients in the Ewing 2008R1 Trial
Authors: Koch Raphael , Haveman Lianne , Ladenstein Ruth , Brichard Benedicte , Jürgens Heribert , Cyprova Sona , van den Berg Henk , Hassenpflug Wolf , Raciborska Anna , Ek Torben , Baumhoer Daniel , Egerer Gerlinde , Kager Leo , Renard Marleen , Hauser Peter , Burdach Stefan , Bovee Judith V.M.G. , Hong Angela M. , Reichardt Peter , Kruseova Jarmila , Streitbürger Arne , Kühne Thomas , Kessler Torsten , Bernkopf Marie , Butterfaß-Bahloul Trude , Dhooge Catharina , Bauer Sebastian , Kiss János , Paulussen Michael , Bonar Fiona , Ranft Andreas , Timmermann Beate , Rascon Jelena , Vieth Volker , Kanerva Jukka , Faldum Andreas , Hartmann Wolfgang , Hjorth Lars , Bhadri Vivek A. , Metzler Markus , Gelderblom Hans , Dirksen Uta
Published: December 2023

Representativeness of Study Participants
Supplementary Figure S4 from Zoledronic Acid Add-on Therapy for Standard-Risk Ewing Sarcoma Patients in the Ewing 2008R1 Trial
Authors: Koch Raphael , Haveman Lianne , Ladenstein Ruth , Brichard Benedicte , Jürgens Heribert , Cyprova Sona , van den Berg Henk , Hassenpflug Wolf , Raciborska Anna , Ek Torben , Baumhoer Daniel , Egerer Gerlinde , Kager Leo , Renard Marleen , Hauser Peter , Burdach Stefan , Bovee Judith V.M.G. , Hong Angela M. , Reichardt Peter , Kruseova Jarmila , Streitbürger Arne , Kühne Thomas , Kessler Torsten , Bernkopf Marie , Butterfaß-Bahloul Trude , Dhooge Catharina , Bauer Sebastian , Kiss János , Paulussen Michael , Bonar Fiona , Ranft Andreas , Timmermann Beate , Rascon Jelena , Vieth Volker , Kanerva Jukka , Faldum Andreas , Hartmann Wolfgang , Hjorth Lars , Bhadri Vivek A. , Metzler Markus , Gelderblom Hans , Dirksen Uta
Published: December 2023

Cumulative incidence of different components of the event-free survival from randomization, by treatment group
Supplementary Figure S3 from Zoledronic Acid Add-on Therapy for Standard-Risk Ewing Sarcoma Patients in the Ewing 2008R1 Trial
Authors: Koch Raphael , Haveman Lianne , Ladenstein Ruth , Brichard Benedicte , Jürgens Heribert , Cyprova Sona , van den Berg Henk , Hassenpflug Wolf , Raciborska Anna , Ek Torben , Baumhoer Daniel , Egerer Gerlinde , Kager Leo , Renard Marleen , Hauser Peter , Burdach Stefan , Bovee Judith V.M.G. , Hong Angela M. , Reichardt Peter , Kruseova Jarmila , Streitbürger Arne , Kühne Thomas , Kessler Torsten , Bernkopf Marie , Butterfaß-Bahloul Trude , Dhooge Catharina , Bauer Sebastian , Kiss János , Paulussen Michael , Bonar Fiona , Ranft Andreas , Timmermann Beate , Rascon Jelena , Vieth Volker , Kanerva Jukka , Faldum Andreas , Hartmann Wolfgang , Hjorth Lars , Bhadri Vivek A. , Metzler Markus , Gelderblom Hans , Dirksen Uta
Published: December 2023

Distribution of the follow-up duration estimated using reverse Kaplan-Meier method, according to treatment group in the full analysis set.
Supplementary Figure S13 from Genomic Tumor Correlates of Clinical Outcomes Following Organ-Sparing Chemoradiation Therapy for Bladder Cancer
Authors: Kamran Sophia C. , Zhou Yuzhen , Otani Keisuke , Drumm Michael , Otani Yukako , Wu Shulin , Wu Chin-Lee , Feldman Adam S. , Wszolek Matthew , Lee Richard J. , Saylor Philip J. , Lennerz Jochen , Van Allen Eliezer , Willers Henning , Hong Theodore S. , Liu Yang , Davicioni Elai , Gibb Ewan A. , Shipley William U. , Mouw Kent W. , Efstathiou Jason A. , Miyamoto David T.
Published: December 2023

ERCC2 mutations and association with re-modified BI-EFS.
Supplementary Figure S2 from Zoledronic Acid Add-on Therapy for Standard-Risk Ewing Sarcoma Patients in the Ewing 2008R1 Trial
Authors: Koch Raphael , Haveman Lianne , Ladenstein Ruth , Brichard Benedicte , Jürgens Heribert , Cyprova Sona , van den Berg Henk , Hassenpflug Wolf , Raciborska Anna , Ek Torben , Baumhoer Daniel , Egerer Gerlinde , Kager Leo , Renard Marleen , Hauser Peter , Burdach Stefan , Bovee Judith V.M.G. , Hong Angela M. , Reichardt Peter , Kruseova Jarmila , Streitbürger Arne , Kühne Thomas , Kessler Torsten , Bernkopf Marie , Butterfaß-Bahloul Trude , Dhooge Catharina , Bauer Sebastian , Kiss János , Paulussen Michael , Bonar Fiona , Ranft Andreas , Timmermann Beate , Rascon Jelena , Vieth Volker , Kanerva Jukka , Faldum Andreas , Hartmann Wolfgang , Hjorth Lars , Bhadri Vivek A. , Metzler Markus , Gelderblom Hans , Dirksen Uta
Published: December 2023

Follow-up duration among patients still alive at last follow-up, according to the date of randomization
Supplementary Table S4 from Safety and Efficacy of NY-ESO-1 Antigen-Specific T-Cell Receptor Gene-Transduced T Lymphocytes in Patients with Synovial Sarcoma: A Phase I/II Clinical Trial
Authors: Kawai Akira , Ishihara Mikiya , Nakamura Tomoki , Kitano Shigehisa , Iwata Shintaro , Takada Kohichi , Emori Makoto , Kato Koji , Endo Makoto , Matsumoto Yoshihiro , Kakunaga Shigeki , Sato Eiichi , Miyahara Yoshihiro , Morino Kunihiko , Tanaka Shinya , Takahashi Shuichi , Matsuo Fujio , Matsumine Akihiko , Kageyama Shinichi , Ueda Takafumi
Published: December 2023

Representativeness of Study Participants
Supplementary Table S1 from Comprehensive Single-Cell Immune Profiling Defines the Patient Multiple Myeloma Microenvironment Following Oncolytic Virus Therapy in a Phase Ib Trial
Authors: Nawrocki Steffan T. , Olea Julian , Villa Celi Claudia , Dadrastoussi Homa , Wu Kaijin , Tsao-Wei Denice , Colombo Anthony , Coffey Matt , Fernandez Hernandez Eduardo , Chen Xuelian , Nuovo Gerard J. , Carew Jennifer S. , Mohrbacher Ann F. , Fields Paul , Kuhn Peter , Siddiqi Imran , Merchant Akil , Kelly Kevin R.
Published: December 2023

Supplementary Table 1. Detailed IMC panel
Supplementary Figure S1 from Safety and Efficacy of NY-ESO-1 Antigen-Specific T-Cell Receptor Gene-Transduced T Lymphocytes in Patients with Synovial Sarcoma: A Phase I/II Clinical Trial
Authors: Kawai Akira , Ishihara Mikiya , Nakamura Tomoki , Kitano Shigehisa , Iwata Shintaro , Takada Kohichi , Emori Makoto , Kato Koji , Endo Makoto , Matsumoto Yoshihiro , Kakunaga Shigeki , Sato Eiichi , Miyahara Yoshihiro , Morino Kunihiko , Tanaka Shinya , Takahashi Shuichi , Matsuo Fujio , Matsumine Akihiko , Kageyama Shinichi , Ueda Takafumi
Published: December 2023

Study design
Supplementary Figure S2 from Comprehensive Single-Cell Immune Profiling Defines the Patient Multiple Myeloma Microenvironment Following Oncolytic Virus Therapy in a Phase Ib Trial
Authors: Nawrocki Steffan T. , Olea Julian , Villa Celi Claudia , Dadrastoussi Homa , Wu Kaijin , Tsao-Wei Denice , Colombo Anthony , Coffey Matt , Fernandez Hernandez Eduardo , Chen Xuelian , Nuovo Gerard J. , Carew Jennifer S. , Mohrbacher Ann F. , Fields Paul , Kuhn Peter , Siddiqi Imran , Merchant Akil , Kelly Kevin R.
Published: December 2023

Supplementary Figure 2. TCR analysis
Supplementary Tables S9 from SNP of Aromatase Predict Long-term Survival and Aromatase Inhibitor Toxicity in Patients with Early Breast Cancer: A Biomarker Analysis of the GIM4 and GIM5 Trials
Authors: Conte Benedetta , Boni Luca , Bisagni Giancarlo , Durando Antonio , Sanna Giovanni , Gori Stefania , Garrone Ornella , Tamberi Stefano , De Placido Sabino , Schettini Francesco , Pazzola Antonio , Ponzone Riccardo , Montemurro Filippo , Lunardi Gianluigi , Notaro Rosario , De Angioletti Maria , Turletti Anna , Mansutti Mauro , Puglisi Fabio , Frassoldati Antonio , Porpiglia Mauro , Fabi Alessandra , Generali Daniele , Scognamiglio Giovanni , Rossi Maura , Brasó-Maristany Fara , Prat Aleix , Cardinali Barbara , Piccioli Patrizia , Serra Martina , Lastraioli Sonia , Bighin Claudia , Poggio Francesca , Lambertini Matteo , Del Mastro Lucia
Published: December 2023

Univariate analyses for DFS in GIM5, GIM4 short arm, and GIM4 long arm cohorts
Supplementary Table S1 from Phase II Trial of Nivolumab in Metastatic Rare Cancer with dMMR or MSI-H and Relation with Immune Phenotypic Analysis (the ROCK Trial)
Authors: Okuma Hitomi S. , Watanabe Keisuke , Tsuchihashi Kenji , Machida Ryunosuke , Sadachi Ryo , Hirakawa Akihiro , Ariyama Hiroshi , Kanai Masashi , Kamikura Masahisa , Anjo Kenta , Hiramitsu Akari , Sekine Shigeki , Okita Natsuko , Mano Hiroyuki , Nishikawa Hiroyoshi , Nakamura Kenichi , Yonemori Kan
Published: December 2023

Supplementary Table S1 Antibodies used for immune phenotype analysis of peripheral blood mononuclear cells
Supplementary Figure S4 from Phase II Trial of Nivolumab in Metastatic Rare Cancer with dMMR or MSI-H and Relation with Immune Phenotypic Analysis (the ROCK Trial)
Authors: Okuma Hitomi S. , Watanabe Keisuke , Tsuchihashi Kenji , Machida Ryunosuke , Sadachi Ryo , Hirakawa Akihiro , Ariyama Hiroshi , Kanai Masashi , Kamikura Masahisa , Anjo Kenta , Hiramitsu Akari , Sekine Shigeki , Okita Natsuko , Mano Hiroyuki , Nishikawa Hiroyoshi , Nakamura Kenichi , Yonemori Kan
Published: December 2023

Supplementary Figure S4: Heat map representation of each parameter in the tSNE plots.
Supplementary Table S1 from SNP of Aromatase Predict Long-term Survival and Aromatase Inhibitor Toxicity in Patients with Early Breast Cancer: A Biomarker Analysis of the GIM4 and GIM5 Trials
Authors: Conte Benedetta , Boni Luca , Bisagni Giancarlo , Durando Antonio , Sanna Giovanni , Gori Stefania , Garrone Ornella , Tamberi Stefano , De Placido Sabino , Schettini Francesco , Pazzola Antonio , Ponzone Riccardo , Montemurro Filippo , Lunardi Gianluigi , Notaro Rosario , De Angioletti Maria , Turletti Anna , Mansutti Mauro , Puglisi Fabio , Frassoldati Antonio , Porpiglia Mauro , Fabi Alessandra , Generali Daniele , Scognamiglio Giovanni , Rossi Maura , Brasó-Maristany Fara , Prat Aleix , Cardinali Barbara , Piccioli Patrizia , Serra Martina , Lastraioli Sonia , Bighin Claudia , Poggio Francesca , Lambertini Matteo , Del Mastro Lucia
Published: December 2023

Representativeness of Study Participants
Supplementary Table S1 from Hyper-Dependence on NHEJ Enables Synergy between DNA-PK Inhibitors and Low-Dose Doxorubicin in Leiomyosarcoma
Authors: Marino-Enriquez Adrian , Novotny Jan Philipp , Gulhan Doga C. , Klooster Isabella , Tran Antuan V. , Kasbo Macy , Lundberg Meijun Z. , Ou Wen-Bin , Tao Derrick L. , Pilco-Janeta Daniel F. , Mao Victor Y. , Zenke Frank T. , Leeper Brittaney A. , Gokhale Prafulla C. , Cowley Glenn S. , Baker Laurence H. , Ballman Karla V. , Root David E. , Albers Joachim , Park Peter J. , George Suzanne , Fletcher Jonathan A.
Published: December 2023

Supplementary Table S1:
Cancer-associated genes interrogated by Oncopanel. Samples in this study were analyzed with three versions of the assay (v1, v2, v3 and v3.1) – the gene content of each panel is indicated
Supplementary Figure S6 from Hyper-Dependence on NHEJ Enables Synergy between DNA-PK Inhibitors and Low-Dose Doxorubicin in Leiomyosarcoma
Authors: Marino-Enriquez Adrian , Novotny Jan Philipp , Gulhan Doga C. , Klooster Isabella , Tran Antuan V. , Kasbo Macy , Lundberg Meijun Z. , Ou Wen-Bin , Tao Derrick L. , Pilco-Janeta Daniel F. , Mao Victor Y. , Zenke Frank T. , Leeper Brittaney A. , Gokhale Prafulla C. , Cowley Glenn S. , Baker Laurence H. , Ballman Karla V. , Root David E. , Albers Joachim , Park Peter J. , George Suzanne , Fletcher Jonathan A.
Published: December 2023

Supplementary Figure S6
Representative cell culture images of LMS04 cultures untreated or treated with 2nM doxorubicin, 400 nM peposertib, or the combination of both, utilized for computationally assisted cell culture confluence analysis (See Supplementary Figure S7).
Supplementary Figure S1 from Hyper-Dependence on NHEJ Enables Synergy between DNA-PK Inhibitors and Low-Dose Doxorubicin in Leiomyosarcoma
Authors: Marino-Enriquez Adrian , Novotny Jan Philipp , Gulhan Doga C. , Klooster Isabella , Tran Antuan V. , Kasbo Macy , Lundberg Meijun Z. , Ou Wen-Bin , Tao Derrick L. , Pilco-Janeta Daniel F. , Mao Victor Y. , Zenke Frank T. , Leeper Brittaney A. , Gokhale Prafulla C. , Cowley Glenn S. , Baker Laurence H. , Ballman Karla V. , Root David E. , Albers Joachim , Park Peter J. , George Suzanne , Fletcher Jonathan A.
Published: December 2023

Supplementary Figure S1:
A. Fraction of genome altered (FGA) in non-LMS cancers compared to LMS from GENIE v9.0 (37). B.
FGA in LMS and in other tumor types in the GENIE dataset, including high grade sarcomas.
Figure S8 from Lenvatinib, Toripalimab plus FOLFOX Chemotherapy in Hepatocellular Carcinoma Patients with Extrahepatic Metastasis: A Biomolecular Exploratory, Phase II Trial (LTSC)
Authors: He MinKe , Huang YeXing , Du ZeFeng , Lai ZhiCheng , Ouyang Hanyue , Shen JingXian , Wen DongSheng , Li QiJiong , Zhang YaoJun , Wei Wei , Chen MinShan , Xu Li , Kan Anna , Shi Ming
Published: December 2023

Representative images of patient seven.
Figure S4 from Lenvatinib, Toripalimab plus FOLFOX Chemotherapy in Hepatocellular Carcinoma Patients with Extrahepatic Metastasis: A Biomolecular Exploratory, Phase II Trial (LTSC)
Authors: He MinKe , Huang YeXing , Du ZeFeng , Lai ZhiCheng , Ouyang Hanyue , Shen JingXian , Wen DongSheng , Li QiJiong , Zhang YaoJun , Wei Wei , Chen MinShan , Xu Li , Kan Anna , Shi Ming
Published: December 2023

Representative images of patient three.
Supplementary Figure S4 from CD24hiCD27+ Bregs within Metastatic Lymph Nodes Promote Multidrug Resistance in Breast Cancer
Authors: Huang Huanhuan , Yao Yao , Shen Lesang , Jiang Jingxin , Zhang Ting , Xiong Jia , Li Jiaxin , Sun Shanshan , Zheng Siwei , Jia Fang , Zhou Jun , Yu Xiuyan , Chen Wuzhen , Shen Jun , Xia Wenjie , Shao Xuan , Wang Qingqing , Huang Jian , Ni Chao
Published: December 2023

Fig. S4. CD24hiCD27+ Breg-induced drug resistance in BC is independent of small molecule substances.
Figure S13 from Lenvatinib, Toripalimab plus FOLFOX Chemotherapy in Hepatocellular Carcinoma Patients with Extrahepatic Metastasis: A Biomolecular Exploratory, Phase II Trial (LTSC)
Authors: He MinKe , Huang YeXing , Du ZeFeng , Lai ZhiCheng , Ouyang Hanyue , Shen JingXian , Wen DongSheng , Li QiJiong , Zhang YaoJun , Wei Wei , Chen MinShan , Xu Li , Kan Anna , Shi Ming
Published: December 2023

Characterization of immune cells.
Supplementary Figure S12 from CD24hiCD27+ Bregs within Metastatic Lymph Nodes Promote Multidrug Resistance in Breast Cancer
Authors: Huang Huanhuan , Yao Yao , Shen Lesang , Jiang Jingxin , Zhang Ting , Xiong Jia , Li Jiaxin , Sun Shanshan , Zheng Siwei , Jia Fang , Zhou Jun , Yu Xiuyan , Chen Wuzhen , Shen Jun , Xia Wenjie , Shao Xuan , Wang Qingqing , Huang Jian , Ni Chao
Published: December 2023

Fig. S12. The addition of anti-PD1/PD-L1 to neoadjuvant chemotherapy improves the pCR rate of patients with mLNs.
Figure S1 from Lenvatinib, Toripalimab plus FOLFOX Chemotherapy in Hepatocellular Carcinoma Patients with Extrahepatic Metastasis: A Biomolecular Exploratory, Phase II Trial (LTSC)
Authors: He MinKe , Huang YeXing , Du ZeFeng , Lai ZhiCheng , Ouyang Hanyue , Shen JingXian , Wen DongSheng , Li QiJiong , Zhang YaoJun , Wei Wei , Chen MinShan , Xu Li , Kan Anna , Shi Ming
Published: December 2023

Clinical trial design and flow diagram.
Figure S1 from Deuterium Magnetic Resonance Imaging Using Deuterated Water-Induced 2H-Tissue Labeling Allows Monitoring Cancer Treatment at Clinical Field Strength
Authors: Asano Hirofumi , Elhelaly Abdelazim Elsayed , Hyodo Fuminori , Iwasaki Ryota , Noda Yoshifumi , Kato Hiroki , Ichihashi Koki , Tomita Hiroyuki , Murata Masaharu , Mori Takashi , Matsuo Masayuki
Published: December 2023

Sensitivity of in vivo deuterium MRI and kinetics of 2H enrichments in C26 xenograft-bearing BALB/c-nu mice allowed to drink D2O freely
(A) Representative coronal deuterium MRI images of the distribution of 2H in the body of C26 colorectal carcinoma xenograft-bearing mice during 10 days of D2O administration. Images were collected on days 1, 3, 7, and 10 of the first exposure to D2O. (B) Representative T1-weighted MRI images of mouse body parts. (C) Full-body MRI images after placing the MRI images of three body parts together show the distribution of 2H and 1H signals collected throughout the body. (D) Quantification of 2H MRI signals of body tissues. Analysis was performed using Image J software. The data show the means ± SD (n=5).
Data from A Phase I Expansion Cohort Study Evaluating the Safety and Efficacy of the CHK1 Inhibitor LY2880070 with Low-dose Gemcitabine in Patients with Metastatic Pancreatic Adenocarcinoma
Authors: Huffman Brandon M. , Feng Hanrong , Parmar Kalindi , Wang Junning , Kapner Kevin S. , Kochupurakkal Bose , Martignetti David B. , Sadatrezaei Golbahar , Abrams Thomas A. , Biller Leah H. , Giannakis Marios , Ng Kimmie , Patel Anuj K. , Perez Kimberly J. , Singh Harshabad , Rubinson Douglas A. , Schlechter Benjamin L. , Andrews Elizabeth , Hannigan Alison M. , Dunwell Stanley , Getchell Zoe , Raghavan Srivatsan , Wolpin Brian M. , Fortier Caroline , D'Andrea Alan D. , Aguirre Andrew J. , Shapiro Geoffrey I. , Cleary James M.
Published: December 2023

AbstractPurpose:
Combining gemcitabine with CHK1 inhibition has shown promise in preclinical models of pancreatic ductal adenocarcinoma (PDAC). Here, we report the findings from a phase I expansion cohort study (NCT02632448) investigating low-dose gemcitabine combined with the CHK1 inhibitor LY2880070 in patients with previously treated advanced PDAC.
Patients and Methods:
Patients with metastatic PDAC were treated with gemcitabine intravenously at 100 mg/m2 on days 1, 8, and 15, and LY2880070 50 mg orally twice daily on days 2–6, 9–13, and 16–20 of each 21-day cycle. Pretreatment tumor biopsies were obtained from each patient for correlative studies and generation of organoid cultures for drug sensitivity testing and biomarker analyses.
Results:
Eleven patients with PDAC were enrolled in the expansion cohort between August 27, 2020 and July 30, 2021. Four patients (36%) experienced drug-related grade 3 adverse events. No objective radiologic responses were observed, and all patients discontinued the trial by 3.2 months. In contrast to the lack of efficacy observed in patients, organoid cultures derived from biopsies procured from two patients demonstrated strong sensitivity to the gemcitabine/LY2880070 combination and showed treatment-induced upregulation of replication stress and DNA damage biomarkers, including pKAP1, pRPA32, and γH2AX, as well as induction of replication fork instability.
Conclusions:
No evidence of clinical activity was observed for combined low-dose gemcitabine and LY2880070 in this treatment-refractory PDAC cohort. However, the gemcitabine/LY2880070 combination showed in vitro efficacy, suggesting that drug sensitivity for this combination in organoid cultures may not predict clinical benefit in patients.
Data from A PERK-Specific Inhibitor Blocks Metastatic Progression by Limiting Integrated Stress Response–Dependent Survival of Quiescent Cancer Cells
Authors: Calvo Veronica , Zheng Wei , Adam-Artigues Anna , Staschke Kirk A. , Huang Xin , Cheung Julie F. , Nobre Ana Rita , Fujisawa Sho , Liu David , Fumagalli Maria , Surguladze David , Stokes Michael E. , Nowacek Ari , Mulvihill Mark , Farias Eduardo F. , Aguirre-Ghiso Julio A.
Published: December 2023

AbstractPurpose:
The integrated stress response (ISR) kinase PERK serves as a survival factor for both proliferative and dormant cancer cells. We aim to validate PERK inhibition as a new strategy to specifically eliminate solitary disseminated cancer cells (DCC) in secondary sites that eventually reawake and originate metastasis.
Experimental Design:
A novel clinical-grade PERK inhibitor (HC4) was tested in mouse syngeneic and PDX models that present quiescent/dormant DCCs or growth-arrested cancer cells in micro-metastatic lesions that upregulate ISR.
Results:
HC4 significantly blocks metastasis, by killing quiescent/slow-cycling ISRhigh, but not proliferative ISRlow DCCs. HC4 blocked expansion of established micro-metastasis that contained ISRhigh slow-cycling cells. Single-cell gene expression profiling and imaging revealed that a significant proportion of solitary DCCs in lungs were indeed dormant and displayed an unresolved ER stress as revealed by high expression of a PERK-regulated signature. In human breast cancer metastasis biopsies, GADD34 expression (PERK-regulated gene) and quiescence were positively correlated. HC4 effectively eradicated dormant bone marrow DCCs, which usually persist after rounds of therapies. Importantly, treatment with CDK4/6 inhibitors (to force a quiescent state) followed by HC4 further reduced metastatic burden. In HNSCC and HER2+ cancers HC4 caused cell death in dormant DCCs. In HER2+ tumors, PERK inhibition caused killing by reducing HER2 activity because of sub-optimal HER2 trafficking and phosphorylation in response to EGF.
Conclusions:
Our data identify PERK as a unique vulnerability in quiescent or slow-cycling ISRhigh DCCs. The use of PERK inhibitors may allow targeting of pre-existing or therapy-induced growth arrested “persister” cells that escape anti-proliferative therapies.
Data from Zoledronic Acid Add-on Therapy for Standard-Risk Ewing Sarcoma Patients in the Ewing 2008R1 Trial
Authors: Koch Raphael , Haveman Lianne , Ladenstein Ruth , Brichard Benedicte , Jürgens Heribert , Cyprova Sona , van den Berg Henk , Hassenpflug Wolf , Raciborska Anna , Ek Torben , Baumhoer Daniel , Egerer Gerlinde , Kager Leo , Renard Marleen , Hauser Peter , Burdach Stefan , Bovee Judith V.M.G. , Hong Angela M. , Reichardt Peter , Kruseova Jarmila , Streitbürger Arne , Kühne Thomas , Kessler Torsten , Bernkopf Marie , Butterfaß-Bahloul Trude , Dhooge Catharina , Bauer Sebastian , Kiss János , Paulussen Michael , Bonar Fiona , Ranft Andreas , Timmermann Beate , Rascon Jelena , Vieth Volker , Kanerva Jukka , Faldum Andreas , Hartmann Wolfgang , Hjorth Lars , Bhadri Vivek A. , Metzler Markus , Gelderblom Hans , Dirksen Uta
Published: December 2023

AbstractPurpose:
The phase III, open-label, prospective, multicenter, randomized Ewing 2008R1 trial (EudraCT2008-003658-13) was conducted in 12 countries to evaluate the effect of zoledronic acid (ZOL) maintenance therapy compared with no add-on regarding event-free survival (EFS, primary endpoint) and overall survival (OS) in standard-risk Ewing sarcoma (EWS).
Patients and Methods:
Eligible patients had localized EWS with either good histologic response to induction chemotherapy and/or small tumors (<200 mL). Patients received six cycles of VIDE induction and eight cycles of VAI (male) or eight cycles of VAC (female) consolidation. ZOL treatment started parallel to the sixth consolidation cycle. Randomization was stratified by tumor site (pelvis/other). The two-sided adaptive inverse–normal four-stage design (planned sample size 448 patients, significance level 5%, power 80%) was changed after the first interim analysis using the Müller–Schäfer method.
Results:
Between April 2010 and November 2018, 284 patients were randomized (142 ZOL/142 no add-on). With a median follow-up of 3.9 years, EFS was not significantly different between ZOL and no add-on group in the adaptive design (HR, 0.74; 95% CI, 0.43–1.28, P = 0.27, intention-to-treat). Three-year EFS rates were 84.0% (95% CI, 77.7%–90.8%) for ZOL vs. 81.7% (95% CI, 75.2%–88.8%) for no add-on. Results were similar in the per-protocol collective. OS was not different between groups. The 3-year OS was 92.8% (95% CI, 88.4%–97.5%) for ZOL and 94.6% (95% CI, 90.9%–98.6%) for no add-on. Noticeable more renal, neurologic, and gastrointestinal toxicities were observed for ZOL (P < 0.05). Severe renal toxicities occurred more often in the ZOL arm (P = 0.003).
Conclusions:
In patients with standard-risk localized EWS, there is no additional benefit from maintenance treatment with ZOL.
Data from Safety and Efficacy of NY-ESO-1 Antigen-Specific T-Cell Receptor Gene-Transduced T Lymphocytes in Patients with Synovial Sarcoma: A Phase I/II Clinical Trial
Authors: Kawai Akira , Ishihara Mikiya , Nakamura Tomoki , Kitano Shigehisa , Iwata Shintaro , Takada Kohichi , Emori Makoto , Kato Koji , Endo Makoto , Matsumoto Yoshihiro , Kakunaga Shigeki , Sato Eiichi , Miyahara Yoshihiro , Morino Kunihiko , Tanaka Shinya , Takahashi Shuichi , Matsuo Fujio , Matsumine Akihiko , Kageyama Shinichi , Ueda Takafumi
Published: December 2023

AbstractPurpose:
To determine, for patients with advanced or recurrent synovial sarcoma (SS) not suitable for surgical resection and resistant to anthracycline, the safety and efficacy of the infusion of autologous T lymphocytes expressing NY-ESO-1 antigen-specific T-cell receptor (TCR) gene and siRNA to inhibit the expression of endogenous TCR (product code: TBI-1301).
Patients and Methods:
Eligible Japanese patients (HLA-A*02:01 or *02:06, NY-ESO-1-positive tumor expression) received cyclophosphamide 750 mg/m2 on days −3 and −2 (induction period) followed by a single dose of 5×109 (±30%) TBI-1301 cells as a divided infusion on days 0 and 1 (treatment period). Primary endpoints were safety-related (phase I) and efficacy-related [objective response rate (ORR) by RECIST v1.1/immune-related RECIST (irRECIST); phase II]. Safety- and efficacy-related secondary endpoints were considered in both phase I/II parts.
Results:
For the full analysis set (N = 8; phase I, n = 3; phase II, n = 5), the ORR was 50.0% (95% confidence interval, 15.7–84.3) with best overall partial response in four of eight patients according to RECIST v1.1/irRECIST. All patients experienced adverse events and seven of eight patients (87.5%) had adverse drug reactions, but no deaths were attributed to adverse events. Cytokine release syndrome occurred in four of eight patients (50.0%), but all cases recovered with prespecified treatment. Immune effector cell-associated neurotoxicity syndrome, replication-competent retrovirus, and lymphocyte clonality were absent.
Conclusions:
Adoptive immunotherapy with TBI-1301 to selectively target NY-ESO-1-positive tumor cells appears to be a promising strategy for the treatment of advanced or recurrent SS with acceptable toxicity.
Data from Comprehensive Single-Cell Immune Profiling Defines the Patient Multiple Myeloma Microenvironment Following Oncolytic Virus Therapy in a Phase Ib Trial
Authors: Nawrocki Steffan T. , Olea Julian , Villa Celi Claudia , Dadrastoussi Homa , Wu Kaijin , Tsao-Wei Denice , Colombo Anthony , Coffey Matt , Fernandez Hernandez Eduardo , Chen Xuelian , Nuovo Gerard J. , Carew Jennifer S. , Mohrbacher Ann F. , Fields Paul , Kuhn Peter , Siddiqi Imran , Merchant Akil , Kelly Kevin R.
Published: December 2023

AbstractPurpose:
Our preclinical studies showed that the oncolytic reovirus formulation pelareorep (PELA) has significant immunomodulatory anti-myeloma activity. We conducted an investigator-initiated clinical trial to evaluate PELA in combination with dexamethasone (Dex) and bortezomib (BZ) and define the tumor immune microenvironment (TiME) in patients with multiple myeloma treated with this regimen.
Patients and Methods:
Patients with relapsed/refractory multiple myeloma (n = 14) were enrolled in a phase Ib clinical trial (ClinicalTrials.gov: NCT02514382) of three escalating PELA doses administered on Days 1, 2, 8, 9, 15, and 16. Patients received 40 mg Dex and 1.5 mg/m2 BZ on Days 1, 8, and 15. Cycles were repeated every 28 days. Pre- and posttreatment bone marrow specimens (IHC, n = 9; imaging mass cytometry, n = 6) and peripheral blood samples were collected for analysis (flow cytometry, n = 5; T-cell receptor clonality, n = 7; cytokine assay, n = 7).
Results:
PELA/BZ/Dex was well-tolerated in all patients. Treatment-emergent toxicities were transient, and no dose-limiting toxicities occurred. Six (55%) of 11 response-evaluable patients showed decreased paraprotein. Treatment increased T and natural killer cell activation, inflammatory cytokine release, and programmed death-ligand 1 expression in bone marrow. Compared with nonresponders, responders had higher reovirus protein levels, increased cytotoxic T-cell infiltration posttreatment, cytotoxic T cells in significantly closer proximity to multiple myeloma cells, and larger populations of a novel immune-primed multiple myeloma phenotype (CD138+ IDO1+HLA-ABCHigh), indicating immunomodulation.
Conclusions:
PELA/BZ/Dex is well-tolerated and associated with anti–multiple myeloma activity in a subset of responding patients, characterized by immune reprogramming and TiME changes, warranting further investigation of PELA as an immunomodulator.
Data from SNP of Aromatase Predict Long-term Survival and Aromatase Inhibitor Toxicity in Patients with Early Breast Cancer: A Biomarker Analysis of the GIM4 and GIM5 Trials
Authors: Conte Benedetta , Boni Luca , Bisagni Giancarlo , Durando Antonio , Sanna Giovanni , Gori Stefania , Garrone Ornella , Tamberi Stefano , De Placido Sabino , Schettini Francesco , Pazzola Antonio , Ponzone Riccardo , Montemurro Filippo , Lunardi Gianluigi , Notaro Rosario , De Angioletti Maria , Turletti Anna , Mansutti Mauro , Puglisi Fabio , Frassoldati Antonio , Porpiglia Mauro , Fabi Alessandra , Generali Daniele , Scognamiglio Giovanni , Rossi Maura , Brasó-Maristany Fara , Prat Aleix , Cardinali Barbara , Piccioli Patrizia , Serra Martina , Lastraioli Sonia , Bighin Claudia , Poggio Francesca , Lambertini Matteo , Del Mastro Lucia
Published: December 2023

AbstractPurpose:
In estrogen receptor–positive (ER+) breast cancer, single-nucleotide polymorphisms (SNP) in the aromatase gene might affect aromatase inhibitors (AI) metabolism and efficacy. Here, we assessed the impact of SNP on prognosis and toxicity of patients receiving adjuvant letrozole.
Experimental Design:
We enrolled 886 postmenopausal patients in the study. They were treated with letrozole for 2 to 5 years after taking tamoxifen for 2 to 6 years, continuing until they completed 5 to 10 years of therapy. Germline DNA was genotyped for SNP rs4646, rs10046, rs749292, and rs727479. Log-rank test and Cox model were used for disease-free survival (DFS) and overall survival (OS). Cumulative incidence (CI) of breast cancer metastasis was assessed through competing risk analysis, with contralateral breast cancer, second malignancies and non-breast cancer death as competing events. CI of skeletal and cardiovascular events were assessed using DFS events as competing events. Subdistribution HR (sHR) with 95% confidence intervals were calculated through Fine-Gray method.
Results:
No SNP was associated with DFS. Variants rs10046 [sHR 2.03, (1.04–2.94)], rs749292 [sHR 2.11, (1.12–3.94)], and rs727479 [sHR 2.62, (1.17–5.83)] were associated with breast cancer metastasis. Three groups were identified on the basis of the number of these variants (0, 1, >1). Variant-based groups were associated with breast cancer metastasis (10-year CI 2.5%, 7.6%, 10.7%, P = 0.035) and OS (10-year estimates 96.5%, 93.0%, 89.6%, P = 0.030). Co-occurrence of rs10046 and rs749292 was negatively associated with 10-year CI of skeletal events (3.2% vs. 10%, P = 0.033). A similar association emerged between rs727479 and cardiovascular events (0.3% vs. 2.1%, P = 0.026).
Conclusions:
SNP of aromatase gene predict risk of metastasis and AI-related toxicity in ER+ early breast cancer, opening an opportunity for better treatment individualization.
Data from CD24hiCD27+ Bregs within Metastatic Lymph Nodes Promote Multidrug Resistance in Breast Cancer
Authors: Huang Huanhuan , Yao Yao , Shen Lesang , Jiang Jingxin , Zhang Ting , Xiong Jia , Li Jiaxin , Sun Shanshan , Zheng Siwei , Jia Fang , Zhou Jun , Yu Xiuyan , Chen Wuzhen , Shen Jun , Xia Wenjie , Shao Xuan , Wang Qingqing , Huang Jian , Ni Chao
Published: December 2023

AbstractPurpose:
Axillary lymph nodes (LN) are the primary and dominant metastatic sites in breast cancer. However, the interaction between tumor cells and immune cells within metastatic LNs (mLN) remains poorly understood. In our study, we explored the effect of CD24hiCD27+ regulatory B cells (Breg) within mLNs on orchestrating drug resistance of breast cancer cells.
Experimental Design:
We collected mLN samples from patients with breast cancer who had received standard neoadjuvant therapy (NAT) and analyzed the spatial features of CD24hiCD27+ Bregs through multicolor immunofluorescence staining. The effect of CD24hiCD27+ Bregs on drug resistance of breast cancer cells was evaluated via in vitro experiments. A mouse model with mLNs was used to evaluate the strategies with blocking the interactions between Bregs and breast cancer for improving tumor regression within mLNs.
Results:
In patients with breast cancer who had received NAT, there is a close spatial correlation between activated CD24hiCD27+ Bregs and residual tumor cells within mLNs. Mechanistically, CD24hiCD27+ Bregs greatly enhance the acquisition of multidrug resistance and stem-like features of breast cancer cells by secreting IL6 and TNFα. More importantly, breast cancer cells further promote the activation of CD24hiCD27+ Bregs via CD40L-dependent and PD-L1–dependent proximal signals, forming a positive feedback pattern. PD-L1 blockade significantly attenuates the drug resistance of breast cancer cells induced by CD24hiCD27+ Bregs, and addition of anti-PD-L1 antibody to chemotherapy improves tumor cell remission in mLNs.
Conclusions:
Our study reveals the pivotal role of CD24hiCD27+ Bregs in promoting drug resistance by interacting with breast cancer cells in mLNs, providing novel evidence for an improved strategy of chemoimmunotherapy combination for patients with breast cancer with mLNs.
Data from Deuterium Magnetic Resonance Imaging Using Deuterated Water-Induced 2H-Tissue Labeling Allows Monitoring Cancer Treatment at Clinical Field Strength
Authors: Asano Hirofumi , Elhelaly Abdelazim Elsayed , Hyodo Fuminori , Iwasaki Ryota , Noda Yoshifumi , Kato Hiroki , Ichihashi Koki , Tomita Hiroyuki , Murata Masaharu , Mori Takashi , Matsuo Masayuki
Published: December 2023

AbstractPurpose:
An accurate and noninvasive assessment of tumor response following treatment other than traditional anatomical imaging techniques is essential. Deuterium magnetic resonance spectroscopic (MRS) imaging has been demonstrated as an alternative for cancer metabolic imaging by high-field MRI using deuterium-labeled molecules. The study aim was to use 2H tissue labeling and deuterium MRI at clinical field strength for tumor visualization and assessment of three anticancer therapies in pancreatic cancer model mice.
Experimental Design:
MIA PaCa-2 pancreatic carcinoma and C26 colorectal carcinoma models of BALB/c-nu mice was prepared, and repeated deuterium MRI was performed during the first 10 days of free drinking of 30% D2O to track 2H distribution in tissues. 2H accumulation in the tumor after irradiation, bevacizumab administration, or gemcitabine administration was also measured in MIA PaCa-2–bearing mice. Confirmatory proton MRI, ex vivo metabolic hyperpolarization 13C-MRS, and histopathology were performed.
Results:
The mouse's whole-body distribution of 2H was visible 1 day after drinking, and the signal intensity increased daily. Although the tumor size did not change 1 and 3 days after irradiation, the amount of 2H decreased significantly. The 2H image intensity of the tumor also significantly decreased after the administration of bevacizumab or gemcitabine. Metabolic hyperpolarization 13C-MRS, proton MRI, and 2H-NMR spectroscopy confirmed the efficacy of the anticancer treatments.
Conclusions:
Deuterium MRI at 1.5T proved feasible to track 2H distribution throughout mouse tissues during D2O administration and revealed a higher 2H accumulation in the tumor xenografts. This research demonstrated a promising successful method for preliminary assessment of radiotherapy and chemotherapy of cancer.
Supplementary Table S5 from Targeting Aggressive B-cell Lymphomas through Pharmacological Activation of the Mitochondrial Protease OMA1
Authors: Schwarzer Adrian , Oliveira Matheus , Kleppa Marc-Jens , Slattery Scott D. , Anantha Andy , Cooper Alan , Hannink Mark , Schambach Axel , Dörrie Anneke , Kotlyarov Alexey , Gaestel Matthias , Hembrough Todd , Levine Jedd , Luther Michael , Stocum Michael , Stiles Linsey , Weinstock David M. , Liesa Marc , Kostura Matthew J.
Published: December 2023

Spearmans Rank correlation of gene expression with response to compound in the cell line screening data.
Supplementary Table S4 from Targeting Aggressive B-cell Lymphomas through Pharmacological Activation of the Mitochondrial Protease OMA1
Authors: Schwarzer Adrian , Oliveira Matheus , Kleppa Marc-Jens , Slattery Scott D. , Anantha Andy , Cooper Alan , Hannink Mark , Schambach Axel , Dörrie Anneke , Kotlyarov Alexey , Gaestel Matthias , Hembrough Todd , Levine Jedd , Luther Michael , Stocum Michael , Stiles Linsey , Weinstock David M. , Liesa Marc , Kostura Matthew J.
Published: December 2023

Gene level data for Venn Diagram figure of Cell line screening data
TABLE 3 from Optimizing Early-stage Clinical Pharmacology Evaluation to Accelerate Clinical Development of Giredestrant in Advanced Breast Cancer
Authors: Malhi Vikram , Agarwal Priya , Gates Mary R. , Liu Lichuan , Wang Jianshuang , De Bruyn Tom , Lam Scott , Eng-Wong Jennifer , Perez-Moreno Pablo , Chen Ya-Chi , Yu Jiajie
Published: December 2023

Change in 4β-HC concentrations over time, from baseline (cycle 1 day −7) to cycle 4 day 1
TABLE 1 from Optimizing Early-stage Clinical Pharmacology Evaluation to Accelerate Clinical Development of Giredestrant in Advanced Breast Cancer
Authors: Malhi Vikram , Agarwal Priya , Gates Mary R. , Liu Lichuan , Wang Jianshuang , De Bruyn Tom , Lam Scott , Eng-Wong Jennifer , Perez-Moreno Pablo , Chen Ya-Chi , Yu Jiajie
Published: December 2023

Giredestrant single-dose pharmacokinetic parameters (escalation cohorts)
Figure S1 from Optimizing Early-stage Clinical Pharmacology Evaluation to Accelerate Clinical Development of Giredestrant in Advanced Breast Cancer
Authors: Malhi Vikram , Agarwal Priya , Gates Mary R. , Liu Lichuan , Wang Jianshuang , De Bruyn Tom , Lam Scott , Eng-Wong Jennifer , Perez-Moreno Pablo , Chen Ya-Chi , Yu Jiajie
Published: December 2023

Study design. LHRH, luteinizing hormone-releasing hormone.
The Matter of Kidney Biopsy in Monoclonal Gammopathy of Renal Significance: A Case Report of a New Pattern of Immunoglobulin-Storing Histiocytosis
Authors: Randone Paolo , Burdese Manuel , Barreca Antonella , Oliva Stefania , Sanna Enrico , Abbasciano Isabella , Anania Patrizia , Boaglio Elena , Biancone Luigi
Published: December 2023

Monoclonal gammopathy of renal significance (MGRS) represents a group of disorders, characterized by paraproteinemia which causes renal damage. These disorders never meet the diagnostic criteria for multiple myeloma (MM) or lymphoproliferative disease. Crystal-storing histiocytosis is one of the rarest patterns of MGRS, characterized by an accumulation of light chains of crystals within histiocyte’s cytoplasm, located in bone marrow or other extramedullary sites such as the kidney, cornea, or thyme. A very few cases have been described as immunoglobulin-storing histiocytosis (IgSH) without evidence of crystals. In the recent literature, only 3 cases of IgSH have been described so far, none renal. In all cases, these very peculiar histopathological patterns are associated with lymphoproliferative or plasma cellular disorders. Here, we report a very unusual IgSH pattern in a kidney biopsy, which led to prompt detection and early therapeutic intervention, in a patient with otherwise misdiagnosed MGRS.
Long Intervals between Intravitreal Injections Using a Treat-and-Extend Protocol in a Real-Life Context in AMD: The LIRE Study
Authors: Leroux Pierre , Agard Emilie , Billant Jérémy , Levron Antoine , Bouvarel Hugo , Badri Yannis , Douma Ikrame , Pradat Pierre , Dot Corinne
Published: December 2023

Introduction: The aim of the study was to assess the outcome of long treat-and-extend (TE) anti-VEGF intravitreal injection (IVI) intervals (≥every 12 weeks [Q12W]) in neovascular age-related macular degeneration (nAMD). The aims of this retrospective study were to determine the proportion of nAMD eyes treated ≥ Q12W, to analyze their longitudinal, functional, and anatomical outcomes, and to compare functional and anatomical outcomes between eyes that rapidly versus slowly reached a Q12W regimen and between eyes directly treated with versus initiating lately the TE regimen. Methods: All patients receiving IVIs for nAMD were screened. The longitudinal, functional, and anatomical characteristics of Q12W-treated eyes were reported at different timepoints. Results: Ninety-one eyes were included (38% of our total nAMD cohort). The mean TE regimen time to reach a Q12W interval was 20.1 ± 16.2 months. During this time, a mean number of 12.1 ± 9.3 IVIs were needed. The mean best-corrected visual acuity was 68 letters at the time of diagnosis and was maintained (p > 0.05). Eyes that rapidly reached a Q12W interval had a shorter follow-up before TE regimen initiation (p = 0.04) and received fewer IVIs (p = 0.02) than eyes that slowly reached a Q12W interval. Eyes directly treated with the TE regimen reached a Q12W interval more rapidly than eyes with late TE initiation. The neovascularization subtype was not a predictor of outcome in TE-treated eyes. Conclusion: ≥Q12W eyes represent an important part of the nAMD population in our real-life study. No baseline anatomical characteristics were associated with the outcome under a TE regimen, although early TE regimen initiation allowed extending more rapidly the IVI interval.
Developmental Defects of Enamel: A Bibliometric Analysis of the Top 100 Most-Cited Papers
Authors: Andrade-Maia Gabriele , Pereira Túlio Silva , Clementino Luna Chagas , Belém Fernanda Vieira , Torres-Ribeiro Juan Diego , Perazzo Matheus de França , Martins-Júnior Paulo Antônio , Paschoal Marco Aurélio Benini
Published: December 2023

Background: Developmental defects of enamel (DDE) are a result of disturbances during formation and maturation of the enamel. Evaluating the most-cited DDE papers can provide important tools that point to the gaps and strengths of this important topic in dentistry. Summary: This bibliometric study analyzed the 100 most-cited papers on DDE. Using a combined keyword search strategy, the 100 most-cited papers were selected in the Web of Science Core Collection. Papers that addressed any type of DDE were included. The extracted data were title, number of citations, study theme, authorship, journal, type of DDE, type of dentition (primary or permanent), type of diagnosis, study design, year, and country of publication. The bibliometric networks were generated through VOSviewer software. The 100 papers had a range from 78 to 459 citations. The main themes of studies were etiopathogenesis (53%), prevalence and incidence (22%), and diagnosis (8%). The authors with the highest number of citations were Goodman AH and Rose JC (459 citations). Most articles were published in dental journals (47%). The most studied types of DDE were fluorosis and amelogenesis imperfecta in the permanent dentition (47%). Observational (24%) and non-systematic reviews (24%) were the most common study designs and ranged from 1977 to 2019. The country with the highest number of publications was the USA (41%). Key Messages: Most of the top 100 DDE papers were about fluorosis and amelogenesis imperfecta, with top papers from three continents with English as the native language. This topic is of great importance in dentistry, and the need for further studies is highlighted, especially regarding the diagnosis and treatment of some DDEs.
“Não se improvisam museus”: a experiência do Museu Republicano “Convenção de Itu”
Authors: Martins Mariana Esteves
Published: December 2023

Nas últimas décadas, os museus têm sido objetos caros às ciências humanas, já que há a compreensão de que são espaços de elaboração de representações sobre o passado e, por isso, passíveis de serem também historicizados. Essas representações são elaboradas enquanto a própria instituição se forma, em diálogo com seus contextos temporais, sociais, culturais e políticos, bem como com seus diferentes interlocutores e agentes. Assim, conhecer a trajetória de um museu e entendê-la enquanto processo é fundamental para uma análise crítica de sua atuação, principalmente no desenvolvimento do acervo e das exposições. Este artigo filia-se a essa linhagem de pesquisa ao se dedicar à história do Museu Republicano “Convenção de Itu”. Nosso objetivo é entrecruzar a trajetória institucional e a análise do processo de formação das coleções e das exposições deste Museu entre os anos de 1921 e 1946 – ou seja, antecedendo brevemente sua abertura, em 18 de abril de 1923, e finalizando com a gestão de seu primeiro diretor, Afonso Taunay –, de modo a compreender as especificidades deste projeto, hoje centenário, e suas potenciais repercussões na contemporaneidade. Nesse sentido, tomar o Museu Republicano “Convenção de Itu” como projeto de pesquisa foi exercício menos comprometido com o seu caráter político, expresso em seu contexto de criação e no evento que o denomina e que pretende celebrar, mas sobretudo com seu papel na elaboração de uma noção de história, em franco compromisso com os múltiplos momentos de sua época e potencialmente com a atual.