bluuebunny/crossref_metadata_2025 huggingface dataset:
Supplementary Figure S5 from Type 2 Diabetes Mellitus and Efficacy Outcomes from Immune Checkpoint Blockade in Patients with Cancer
Authors: Cortellini Alessio , D'Alessio Antonio , Cleary Siobhan , Buti Sebastiano , Bersanelli Melissa , Bordi Paola , Tonini Giuseppe , Vincenzi Bruno , Tucci Marco , Russo Alessandro , Pantano Francesco , Russano Marco , Stucci Luigia Stefania , Sergi Maria Chiara , Falconi Martina , Zarzana Maria Antonietta , Santini Daniele , Spagnolo Francesco , Tanda Enrica T. , Rastelli Francesca , Giorgi Francesca Chiara , Pergolesi Federica , Giusti Raffaele , Filetti Marco , Lo Bianco Francesca , Marchetti Paolo , Botticelli Andrea , Gelibter Alain , Siringo Marco , Ferrari Marco , Marconcini Riccardo , Vitale Maria Giuseppa , Nicolardi Linda , Chiari Rita , Ghidini Michele , Nigro Olga , Grossi Francesco , De Tursi Michele , Di Marino Pietro , Queirolo Paola , Bracarda Sergio , Macrini Serena , Inno Alessandro , Zoratto Federica , Veltri Enzo , Spoto Chiara , Vitale Maria Grazia , Cannita Katia , Gennari Alessandra , Morganstein Daniel L. , Mallardo Domenico , Nibid Lorenzo , Sabarese Giovanna , Brunetti Leonardo , Perrone Giuseppe , Ascierto Paolo A. , Ficorella Corrado , Pinato David J.
Published: July 2023

Kaplan-Meier survival estimates according to the receipt of no diabetes medication, other diabetes medications/insulin therapy only, and metformin therapy (either alone or in combinations). A) Overall Survival whole cohort; patients not receiving diabetes medications: 18.9 months (95%CI: 15.9-21.6; 684 events), patients on other diabetes medications/insulin therapy only: 19.3 months (95%CI: 11.6-22.9; 48 events), patients on metformin: 12.3 months (95%CI: 9.8-15.9; 100 events). B) Progression Free Survival whole cohort; patients not receiving diabetes medications: 8.2 months (95%CI: 7.1-9.4; 872 events), patients on other diabetes medications/insulin therapy only: 10.7 months (95%CI: 6.7-11.6; 61 events), patients on metformin: 7.9 months (95%CI: 5.1-10.1; 124 events).
Supplementary Figure S4 from Type 2 Diabetes Mellitus and Efficacy Outcomes from Immune Checkpoint Blockade in Patients with Cancer
Authors: Cortellini Alessio , D'Alessio Antonio , Cleary Siobhan , Buti Sebastiano , Bersanelli Melissa , Bordi Paola , Tonini Giuseppe , Vincenzi Bruno , Tucci Marco , Russo Alessandro , Pantano Francesco , Russano Marco , Stucci Luigia Stefania , Sergi Maria Chiara , Falconi Martina , Zarzana Maria Antonietta , Santini Daniele , Spagnolo Francesco , Tanda Enrica T. , Rastelli Francesca , Giorgi Francesca Chiara , Pergolesi Federica , Giusti Raffaele , Filetti Marco , Lo Bianco Francesca , Marchetti Paolo , Botticelli Andrea , Gelibter Alain , Siringo Marco , Ferrari Marco , Marconcini Riccardo , Vitale Maria Giuseppa , Nicolardi Linda , Chiari Rita , Ghidini Michele , Nigro Olga , Grossi Francesco , De Tursi Michele , Di Marino Pietro , Queirolo Paola , Bracarda Sergio , Macrini Serena , Inno Alessandro , Zoratto Federica , Veltri Enzo , Spoto Chiara , Vitale Maria Grazia , Cannita Katia , Gennari Alessandra , Morganstein Daniel L. , Mallardo Domenico , Nibid Lorenzo , Sabarese Giovanna , Brunetti Leonardo , Perrone Giuseppe , Ascierto Paolo A. , Ficorella Corrado , Pinato David J.
Published: July 2023

Kaplan-Meier survival estimates according to the receipt of other diabetes medications and insulin therapy. A) Overall Survival whole cohort; patients on other oral antidiabetic drugs and insulin therapy: 17.5 months (95%CI: 12.8-20.9; 82 events), patients not receiving other oral diabetes medications and insulin therapy 17.8 months (95%CI: 15.4 – 19.7; 750 events). B) Progression Free Survival whole cohort; other oral diabetes medications and insulin therapy: 8.2 months (95%CI: 6.2-11.4; 106 events), patients not receiving other oral diabetes medications and insulin therapy: 8.1 months (95%CI: 7.1 – 9.2; 951 events).
Supplementary Figure S2 from Type 2 Diabetes Mellitus and Efficacy Outcomes from Immune Checkpoint Blockade in Patients with Cancer
Authors: Cortellini Alessio , D'Alessio Antonio , Cleary Siobhan , Buti Sebastiano , Bersanelli Melissa , Bordi Paola , Tonini Giuseppe , Vincenzi Bruno , Tucci Marco , Russo Alessandro , Pantano Francesco , Russano Marco , Stucci Luigia Stefania , Sergi Maria Chiara , Falconi Martina , Zarzana Maria Antonietta , Santini Daniele , Spagnolo Francesco , Tanda Enrica T. , Rastelli Francesca , Giorgi Francesca Chiara , Pergolesi Federica , Giusti Raffaele , Filetti Marco , Lo Bianco Francesca , Marchetti Paolo , Botticelli Andrea , Gelibter Alain , Siringo Marco , Ferrari Marco , Marconcini Riccardo , Vitale Maria Giuseppa , Nicolardi Linda , Chiari Rita , Ghidini Michele , Nigro Olga , Grossi Francesco , De Tursi Michele , Di Marino Pietro , Queirolo Paola , Bracarda Sergio , Macrini Serena , Inno Alessandro , Zoratto Federica , Veltri Enzo , Spoto Chiara , Vitale Maria Grazia , Cannita Katia , Gennari Alessandra , Morganstein Daniel L. , Mallardo Domenico , Nibid Lorenzo , Sabarese Giovanna , Brunetti Leonardo , Perrone Giuseppe , Ascierto Paolo A. , Ficorella Corrado , Pinato David J.
Published: July 2023

Kaplan-Meier survival estimates according to the number of diabetes medications. A) Overall Survival whole cohort; patients on more than one diabetes medications: 15.5 months (95%CI: 11.1-20.6; 79 events), patients on one medication: 12.5 months (95%CI: 10.0 – 18.9; 69 events), patients not receiving diabetes medications: 18.9 months (95%CI: 15.9 – 21.5; 684 events). B) Progression Free Survival whole cohort; patients on more than one diabetes medications: 7.9 months (95%CI: 6.2-11.4; 101 events), patients on one medication: 8.4 months (95%CI: 4.9 – 11.9; 84 events), patients not receiving diabetes medications: 8.2 months (95%CI: 7.1 – 9.4; 872 events). Polypharmacy: more than one diabetes medication.
Supplementary Tables 1-8 from ALK Amplification and Rearrangements Are Recurrent Targetable Events in Congenital and Adult Glioblastoma
Authors: Blandin Anne-Florence , Giglio Ross , Graham Maya Srikanth , Garcia Guadalupe , Malinowski Seth , Woods Jared K. , Ramkissoon Shakti , Ramkissoon Lori , Dubois Frank , Schoolcraft Kathleen , Tsai Jessica , Wang Dayle , Jones Robert , Vogelzang Jayne , Pelton Kristine , Becker Sarah , Watkinson Fiona , Sinai Claire , Cohen Elizabeth F. , Booker Matthew A. , Tolstorukov Michael Y. , Haemels Veerle , Goumnerova Liliana , Wright Karen , Kieran Mark , Fehnel Katie , Reardon David , Tauziede-Espariat Arnault , Lulla Rishi , Carcamo Benjamin , Chaleff Stanley , Charest Alain , De Smet Frederik , Ligon Azra H. , Dubuc Adrian , Pages Melanie , Varlet Pascale , Wen Patrick Y. , Alexander Brian M. , Chi Susan , Alexandrescu Sanda , Kittler Ralf , Bachoo Robert , Bandopadhayay Pratiti , Beroukhim Rameen , Ligon Keith L.
Published: July 2023

Additional information tables 1 to 8.
Supplementary Figure 6 from ALK Amplification and Rearrangements Are Recurrent Targetable Events in Congenital and Adult Glioblastoma
Authors: Blandin Anne-Florence , Giglio Ross , Graham Maya Srikanth , Garcia Guadalupe , Malinowski Seth , Woods Jared K. , Ramkissoon Shakti , Ramkissoon Lori , Dubois Frank , Schoolcraft Kathleen , Tsai Jessica , Wang Dayle , Jones Robert , Vogelzang Jayne , Pelton Kristine , Becker Sarah , Watkinson Fiona , Sinai Claire , Cohen Elizabeth F. , Booker Matthew A. , Tolstorukov Michael Y. , Haemels Veerle , Goumnerova Liliana , Wright Karen , Kieran Mark , Fehnel Katie , Reardon David , Tauziede-Espariat Arnault , Lulla Rishi , Carcamo Benjamin , Chaleff Stanley , Charest Alain , De Smet Frederik , Ligon Azra H. , Dubuc Adrian , Pages Melanie , Varlet Pascale , Wen Patrick Y. , Alexander Brian M. , Chi Susan , Alexandrescu Sanda , Kittler Ralf , Bachoo Robert , Bandopadhayay Pratiti , Beroukhim Rameen , Ligon Keith L.
Published: July 2023

Supplementary Figure 6: Single cell RNA sequencing comparison of ALK expression and other infant/pediatric glioma kinase drivers in developing human and mouse brain. A. 2D representation of human brain cell subtypes (48 samples) during cortex development using a single cell RNA-seq atlas (http://cells.ucsc.edu/?ds=cortex-dev) shows that ALK positive cells make up less than 1% of all cells in the dataset and aren't localized within a specific cluster.B. Cluster-level summary of the human scRNA dataset shows that ALK expression (TPM) is decreased compared to EGFR, NTRK2, and NTRK3, and ALK positive cells make up a much lower percentage of each cluster compared to those 3 genes.C. 2D representation of developmental mouse forebrain (E12.5 – P6) in a single cell RNA-seq atlas (http://cc-shiny-01.functionalgenomics.ca/braindex/clusters) shows similar results as seen in the human scRNA Nowakowski dataset.D. Cluster-level summary of the mouse scRNA dataset corroborates results seen in the Nowkowski scRNA dataset; that Alk expression (log-normalized) is decreased, and less prevalent than EGFR, NTRK2, and NTRK3.E. 2D representation of RNA sequencing data for NTRK1-3 genes in the Nowakowski developing human cortex dataset. Compared to ALK expression, the NTRK genes have increased expression levels, increased prevalence in the dataset, and show increased localization to specific cluster.F. Similar to (E), the 2D representation of Ntrk genes in the developing mouse scRNA dataset shows increased expression and prevalence compared to Alk.
Supplementary Figure 4 from ALK Amplification and Rearrangements Are Recurrent Targetable Events in Congenital and Adult Glioblastoma
Authors: Blandin Anne-Florence , Giglio Ross , Graham Maya Srikanth , Garcia Guadalupe , Malinowski Seth , Woods Jared K. , Ramkissoon Shakti , Ramkissoon Lori , Dubois Frank , Schoolcraft Kathleen , Tsai Jessica , Wang Dayle , Jones Robert , Vogelzang Jayne , Pelton Kristine , Becker Sarah , Watkinson Fiona , Sinai Claire , Cohen Elizabeth F. , Booker Matthew A. , Tolstorukov Michael Y. , Haemels Veerle , Goumnerova Liliana , Wright Karen , Kieran Mark , Fehnel Katie , Reardon David , Tauziede-Espariat Arnault , Lulla Rishi , Carcamo Benjamin , Chaleff Stanley , Charest Alain , De Smet Frederik , Ligon Azra H. , Dubuc Adrian , Pages Melanie , Varlet Pascale , Wen Patrick Y. , Alexander Brian M. , Chi Susan , Alexandrescu Sanda , Kittler Ralf , Bachoo Robert , Bandopadhayay Pratiti , Beroukhim Rameen , Ligon Keith L.
Published: July 2023

Supplementary Figure 4: Characterization of the lung cancer recurrent DCTN1-ALK fusion identified in cGBM (case ALK.232). A. Integrative Genomic Viewer (IGV) screenshot of the DCTN1-ALK variant.B. Predicted sequence of DCTN1-ALK fusion (DCTN1 exon 1-26, ALK exon 20-29 conserved).C. PDX DCTN1-ALK sub-renal capsule engraftment confimed by IHC.C. Relative viability of the ALK wild-type GBM line (BT164) and BT1857 ceritinib-treated cells versus DMSO control.D. Relative viability of BT164 and BT1857 lorlatinib-treated cells versus DMSO control.E. Relative viability of BT164 and BT1857 cells treated with an EGFR tyrosine kinase inhibitor neratinib.F. PDX DCTN1-ALK sub-renal capsule engraftment confirmed by IHC.
Supplementary Figure 1 from ALK Amplification and Rearrangements Are Recurrent Targetable Events in Congenital and Adult Glioblastoma
Authors: Blandin Anne-Florence , Giglio Ross , Graham Maya Srikanth , Garcia Guadalupe , Malinowski Seth , Woods Jared K. , Ramkissoon Shakti , Ramkissoon Lori , Dubois Frank , Schoolcraft Kathleen , Tsai Jessica , Wang Dayle , Jones Robert , Vogelzang Jayne , Pelton Kristine , Becker Sarah , Watkinson Fiona , Sinai Claire , Cohen Elizabeth F. , Booker Matthew A. , Tolstorukov Michael Y. , Haemels Veerle , Goumnerova Liliana , Wright Karen , Kieran Mark , Fehnel Katie , Reardon David , Tauziede-Espariat Arnault , Lulla Rishi , Carcamo Benjamin , Chaleff Stanley , Charest Alain , De Smet Frederik , Ligon Azra H. , Dubuc Adrian , Pages Melanie , Varlet Pascale , Wen Patrick Y. , Alexander Brian M. , Chi Susan , Alexandrescu Sanda , Kittler Ralf , Bachoo Robert , Bandopadhayay Pratiti , Beroukhim Rameen , Ligon Keith L.
Published: July 2023

Supplementary Figure 1: Characterization of the novel LRRFIP1-ALK fusion (case ALK.223) A. Visualization of the read coverage at the fusion sites in ALK and LRRFIP1 genes using Integrative Genomic Viewer.B. Pile-up plot generated by SvABA using whole-genome sequencing data shows the breakpoint coordinates.C. Copy number ratio profile by WGS showing no somatic copy number alterations anywhere in the genome. The x-axis represents the chromosomes.D. Copy number ratio profile on chromosome 2 showing no copy number change of ALK and LRRFIP1 genes.E. Two RT-PCR products of 186bp (variant 1) and 189bp (variant 3) were detected by agarose gel electrophoresis with total RNA from tumor specimen ALK.223.F. Primer sequences of ALK-LRRFIP1 (variants 1 and 2) and LRRFIP1-ALK (variant 3) and the predicted DNA product size.G. Western Blot analysis of ALK signaling pathway in subcutaneous tumors treated with vehicle or lorlatinib. Normal brain was used as control.H. Representative 40x images and CellProfiler quantification of Cleaved Caspase 3- and Ki-67- stained subcutaneous tumors.
Supplementary Table S5 from Plasma 25-Hydroxyvitamin D Levels and Survival in Stage III Colon Cancer: Findings from CALGB/SWOG 80702 (Alliance)
Authors: Wang Qiao-Li , Ma Chao , Yuan Chen , Shi Qian , Wolpin Brian M. , Zhang Yin , Fuchs Charles S. , Meyer Jeffrey , Zemla Tyler , Cheng En , Kumthekar Priya , Guthrie Katherine A. , Couture Felix , Kuebler Philip , Kumar Pankaj , Tan Benjamin , Krishnamurthi Smitha , Goldberg Richard M. , Venook Alan , Blanke Charles , Shields Anthony F. , O'Reilly Eileen M. , Meyerhardt Jeffrey A. , Ng Kimmie
Published: July 2023

Table S5. Hazard ratio of cancer-specific mortality by plasma 25-hydroxyvitamin D levels in plasma biomarker companion study and by predicted vitamin D scores in diet and lifestyle companion study
Supplementary Table S2 from Plasma 25-Hydroxyvitamin D Levels and Survival in Stage III Colon Cancer: Findings from CALGB/SWOG 80702 (Alliance)
Authors: Wang Qiao-Li , Ma Chao , Yuan Chen , Shi Qian , Wolpin Brian M. , Zhang Yin , Fuchs Charles S. , Meyer Jeffrey , Zemla Tyler , Cheng En , Kumthekar Priya , Guthrie Katherine A. , Couture Felix , Kuebler Philip , Kumar Pankaj , Tan Benjamin , Krishnamurthi Smitha , Goldberg Richard M. , Venook Alan , Blanke Charles , Shields Anthony F. , O'Reilly Eileen M. , Meyerhardt Jeffrey A. , Ng Kimmie
Published: July 2023

Table S2. Representativeness of study participants
Supplementary Table S3. from Multi-Maintenance Olaparib Therapy in Relapsed, Germline BRCA1/2-Mutant High-Grade Serous Ovarian Cancer (MOLTO): A Phase II Trial
Authors: Morgan Robert D. , Clamp Andrew R. , White Daniel J. , Price Marcus , Burghel George J. , Ryder W. David J. , Mahmood Reem D. , Murphy Alexander D. , Hasan Jurjees , Mitchell Claire L. , Salih Zena , Wheeler Chelsey , Buckley Emma , Truelove Joanna , King Georgia , Ainaoui Yasmina , Bhaskar Sanjeev S. , Shaw Joseph , Evans D. Gareth R. , Kilerci Bedirhan , Pearce Simon P. , Brady Gerard , Dive Caroline , O'Connor James P.B. , Wallace Andrew J. , Rothwell Dominic G. , Edmondson Richard J. , Jayson Gordon C.
Published: July 2023

Liquid biopsy time points.
Supplementary Table S1 from Plasma 25-Hydroxyvitamin D Levels and Survival in Stage III Colon Cancer: Findings from CALGB/SWOG 80702 (Alliance)
Authors: Wang Qiao-Li , Ma Chao , Yuan Chen , Shi Qian , Wolpin Brian M. , Zhang Yin , Fuchs Charles S. , Meyer Jeffrey , Zemla Tyler , Cheng En , Kumthekar Priya , Guthrie Katherine A. , Couture Felix , Kuebler Philip , Kumar Pankaj , Tan Benjamin , Krishnamurthi Smitha , Goldberg Richard M. , Venook Alan , Blanke Charles , Shields Anthony F. , O'Reilly Eileen M. , Meyerhardt Jeffrey A. , Ng Kimmie
Published: July 2023

Table S1. Baseline characteristics of study participants in the complete clinical trial, plasma biomarker companion study, and diet and lifestyle companion study
Supplementary Table S1. from Multi-Maintenance Olaparib Therapy in Relapsed, Germline BRCA1/2-Mutant High-Grade Serous Ovarian Cancer (MOLTO): A Phase II Trial
Authors: Morgan Robert D. , Clamp Andrew R. , White Daniel J. , Price Marcus , Burghel George J. , Ryder W. David J. , Mahmood Reem D. , Murphy Alexander D. , Hasan Jurjees , Mitchell Claire L. , Salih Zena , Wheeler Chelsey , Buckley Emma , Truelove Joanna , King Georgia , Ainaoui Yasmina , Bhaskar Sanjeev S. , Shaw Joseph , Evans D. Gareth R. , Kilerci Bedirhan , Pearce Simon P. , Brady Gerard , Dive Caroline , O'Connor James P.B. , Wallace Andrew J. , Rothwell Dominic G. , Edmondson Richard J. , Jayson Gordon C.
Published: July 2023

Serious adverse events.
Supplementary Figure S5. from Multi-Maintenance Olaparib Therapy in Relapsed, Germline BRCA1/2-Mutant High-Grade Serous Ovarian Cancer (MOLTO): A Phase II Trial
Authors: Morgan Robert D. , Clamp Andrew R. , White Daniel J. , Price Marcus , Burghel George J. , Ryder W. David J. , Mahmood Reem D. , Murphy Alexander D. , Hasan Jurjees , Mitchell Claire L. , Salih Zena , Wheeler Chelsey , Buckley Emma , Truelove Joanna , King Georgia , Ainaoui Yasmina , Bhaskar Sanjeev S. , Shaw Joseph , Evans D. Gareth R. , Kilerci Bedirhan , Pearce Simon P. , Brady Gerard , Dive Caroline , O'Connor James P.B. , Wallace Andrew J. , Rothwell Dominic G. , Edmondson Richard J. , Jayson Gordon C.
Published: July 2023

BRCA2 reversion mutation detected in cell-free circulating DNA from patient 16.
Supplementary Figure S3. from Multi-Maintenance Olaparib Therapy in Relapsed, Germline BRCA1/2-Mutant High-Grade Serous Ovarian Cancer (MOLTO): A Phase II Trial
Authors: Morgan Robert D. , Clamp Andrew R. , White Daniel J. , Price Marcus , Burghel George J. , Ryder W. David J. , Mahmood Reem D. , Murphy Alexander D. , Hasan Jurjees , Mitchell Claire L. , Salih Zena , Wheeler Chelsey , Buckley Emma , Truelove Joanna , King Georgia , Ainaoui Yasmina , Bhaskar Sanjeev S. , Shaw Joseph , Evans D. Gareth R. , Kilerci Bedirhan , Pearce Simon P. , Brady Gerard , Dive Caroline , O'Connor James P.B. , Wallace Andrew J. , Rothwell Dominic G. , Edmondson Richard J. , Jayson Gordon C.
Published: July 2023

Cell-free circulating DNA yields at each time point.
Supplementary Figure S2. from Multi-Maintenance Olaparib Therapy in Relapsed, Germline BRCA1/2-Mutant High-Grade Serous Ovarian Cancer (MOLTO): A Phase II Trial
Authors: Morgan Robert D. , Clamp Andrew R. , White Daniel J. , Price Marcus , Burghel George J. , Ryder W. David J. , Mahmood Reem D. , Murphy Alexander D. , Hasan Jurjees , Mitchell Claire L. , Salih Zena , Wheeler Chelsey , Buckley Emma , Truelove Joanna , King Georgia , Ainaoui Yasmina , Bhaskar Sanjeev S. , Shaw Joseph , Evans D. Gareth R. , Kilerci Bedirhan , Pearce Simon P. , Brady Gerard , Dive Caroline , O'Connor James P.B. , Wallace Andrew J. , Rothwell Dominic G. , Edmondson Richard J. , Jayson Gordon C.
Published: July 2023

Functional homologous recombination repair.
Table S2 from Resolving the Pathogenesis of Anaplastic Wilms Tumors through Spatial Mapping of Cancer Cell Evolution
Authors: Rastegar Bahar , Andersson Natalie , Petersson Alexandra , Karlsson Jenny , Chattopadhyay Subhayan , Valind Anders , Jansson Caroline , Durand Geoffroy , Romerius Patrik , Jirström Karin , Holmquist Mengelbier Linda , Gisselsson David
Published: July 2023

Supplementary Table 2. Representativeness of study participants. Details on how the patients with Wilms tumor in the present study compare to the general population of patients diagnosed with with Wilms tumor.
Supplementary Figure S1. from Multi-Maintenance Olaparib Therapy in Relapsed, Germline BRCA1/2-Mutant High-Grade Serous Ovarian Cancer (MOLTO): A Phase II Trial
Authors: Morgan Robert D. , Clamp Andrew R. , White Daniel J. , Price Marcus , Burghel George J. , Ryder W. David J. , Mahmood Reem D. , Murphy Alexander D. , Hasan Jurjees , Mitchell Claire L. , Salih Zena , Wheeler Chelsey , Buckley Emma , Truelove Joanna , King Georgia , Ainaoui Yasmina , Bhaskar Sanjeev S. , Shaw Joseph , Evans D. Gareth R. , Kilerci Bedirhan , Pearce Simon P. , Brady Gerard , Dive Caroline , O'Connor James P.B. , Wallace Andrew J. , Rothwell Dominic G. , Edmondson Richard J. , Jayson Gordon C.
Published: July 2023

Kaplan Meier curves.
Table S1 from Resolving the Pathogenesis of Anaplastic Wilms Tumors through Spatial Mapping of Cancer Cell Evolution
Authors: Rastegar Bahar , Andersson Natalie , Petersson Alexandra , Karlsson Jenny , Chattopadhyay Subhayan , Valind Anders , Jansson Caroline , Durand Geoffroy , Romerius Patrik , Jirström Karin , Holmquist Mengelbier Linda , Gisselsson David
Published: July 2023

Supplementary Table 1. Overview of the study cohort and the clinical data. This table contains basic clinical information, including age, sex, whether tumors were uni- or bilateral, histology, stage, risk group, treatment to which the resection specimen analyzed was subjected to, the final outcome and the record of adverse events.
Fig S3 from Resolving the Pathogenesis of Anaplastic Wilms Tumors through Spatial Mapping of Cancer Cell Evolution
Authors: Rastegar Bahar , Andersson Natalie , Petersson Alexandra , Karlsson Jenny , Chattopadhyay Subhayan , Valind Anders , Jansson Caroline , Durand Geoffroy , Romerius Patrik , Jirström Karin , Holmquist Mengelbier Linda , Gisselsson David
Published: July 2023

Supplementary Figure 3. Relationship between anaplasia, copy number aberrations, regression and mitotic rate.
Supplementary Table 2 from Metastatic Prostate Cancers with BRCA2 versus ATM Mutations Exhibit Divergent Molecular Features and Clinical Outcomes
Authors: Hwang Justin , Shi Xiaolei , Elliott Andrew , Arnoff Taylor E. , McGrath Julie , Xiu Joanne , Walker Phillip , Bergom Hannah E. , Day Abderrahman , Ahmed Shihab , Tape Sydney , Makovec Allison , Ali Atef , Shaker Rami M. , Toye Eamon , Passow Rachel , Lozada John R. , Wang Jinhua , Lou Emil , Mouw Kent W. , Carneiro Benedito A. , Heath Elisabeth I. , McKay Rana R. , Korn W. Michael , Nabhan Chadi , Ryan Charles J. , Antonarakis Emmanuel S.
Published: July 2023

Comparison of the frequencies of additional molecular features between non-castrate (NC) and castrate (C) samples in ATMm, BRCA2m, HRDother, and HRP groups. The significant differences between the two groups are highlighted (red box).
Supplementary Table 1 from Metastatic Prostate Cancers with BRCA2 versus ATM Mutations Exhibit Divergent Molecular Features and Clinical Outcomes
Authors: Hwang Justin , Shi Xiaolei , Elliott Andrew , Arnoff Taylor E. , McGrath Julie , Xiu Joanne , Walker Phillip , Bergom Hannah E. , Day Abderrahman , Ahmed Shihab , Tape Sydney , Makovec Allison , Ali Atef , Shaker Rami M. , Toye Eamon , Passow Rachel , Lozada John R. , Wang Jinhua , Lou Emil , Mouw Kent W. , Carneiro Benedito A. , Heath Elisabeth I. , McKay Rana R. , Korn W. Michael , Nabhan Chadi , Ryan Charles J. , Antonarakis Emmanuel S.
Published: July 2023

Composition and rates of all detectable genomic features detectable through the Caris diagnostic platform.
Supplementary Fig. 2 from Monitoring Sarcoma Response to Immune Checkpoint Inhibition and Local Cryotherapy with Circulating Tumor DNA Analysis
Authors: Bui Nam Q. , Nemat-Gorgani Neda , Subramanian Ajay , Torres Ileana A. , Lohman Marta , Sears Timothy J. , van de Rijn Matt , Charville Gregory W. , Becker Hans-Christoph , Wang David S. , Hwang Gloria L. , Ganjoo Kristen N. , Moding Everett J.
Published: July 2023

Supplementary Fig. 2
Supplementary Table S4 from TIGIT Expression Delineates T-cell Populations with Distinct Functional and Prognostic Impact in Pancreatic Cancer
Authors: Heiduk Max , Klimova Anna , Reiche Charlotte , Digomann David , Beer Carolin , Aust Daniela E. , Distler Marius , Weitz Jürgen , Seifert Adrian M. , Seifert Lena
Published: July 2023

Proportion of PD-1+ or TIGIT+ cells of CD8+ T cells, Tconv or Treg ± standard deviation in patient blood according to clinicopathological parameters with standard deviation. Statistics (Stat.) with unpaired two-sided t-test or one-way ANOVA, respectively. *, P < 0.05; **, P < 0.01
Supplementary Fig. 1 from Monitoring Sarcoma Response to Immune Checkpoint Inhibition and Local Cryotherapy with Circulating Tumor DNA Analysis
Authors: Bui Nam Q. , Nemat-Gorgani Neda , Subramanian Ajay , Torres Ileana A. , Lohman Marta , Sears Timothy J. , van de Rijn Matt , Charville Gregory W. , Becker Hans-Christoph , Wang David S. , Hwang Gloria L. , Ganjoo Kristen N. , Moding Everett J.
Published: July 2023

Supplementary Fig. 1
Supplementary Table S2 from TIGIT Expression Delineates T-cell Populations with Distinct Functional and Prognostic Impact in Pancreatic Cancer
Authors: Heiduk Max , Klimova Anna , Reiche Charlotte , Digomann David , Beer Carolin , Aust Daniela E. , Distler Marius , Weitz Jürgen , Seifert Adrian M. , Seifert Lena
Published: July 2023

Antibodies used for flow cytometry.
Supplementary Table S1 from TIGIT Expression Delineates T-cell Populations with Distinct Functional and Prognostic Impact in Pancreatic Cancer
Authors: Heiduk Max , Klimova Anna , Reiche Charlotte , Digomann David , Beer Carolin , Aust Daniela E. , Distler Marius , Weitz Jürgen , Seifert Adrian M. , Seifert Lena
Published: July 2023

Clinicopathological characteristics of patients in blood and PDAC cohort.
Supplementary Table S3 from Additional Oncogenic Alterations in RAS-Driven Differentiated Thyroid Cancers Associate with Worse Clinicopathologic Outcomes
Authors: Bikas Athanasios , Ahmadi Sara , Pappa Theodora , Marqusee Ellen , Wong Kristine , Nehs Matthew A. , Cho Nancy L. , Haase Jacob , Doherty Gerard M. , Sehgal Kartik , Barletta Justine A. , Alexander Erik K. , Landa Iñigo
Published: July 2023

Supplementary Table S3. Comparison of clinical and pathologic characteristics of differentiated thyroid cancers with diploid versus heterozygous losses at chromosome 22q
Supplementary Figure S9 from TIGIT Expression Delineates T-cell Populations with Distinct Functional and Prognostic Impact in Pancreatic Cancer
Authors: Heiduk Max , Klimova Anna , Reiche Charlotte , Digomann David , Beer Carolin , Aust Daniela E. , Distler Marius , Weitz Jürgen , Seifert Adrian M. , Seifert Lena
Published: July 2023

General EOMES expression and expression as a function of PD-1 and TIGIT in blood.
Supplementary Table S2 from Additional Oncogenic Alterations in RAS-Driven Differentiated Thyroid Cancers Associate with Worse Clinicopathologic Outcomes
Authors: Bikas Athanasios , Ahmadi Sara , Pappa Theodora , Marqusee Ellen , Wong Kristine , Nehs Matthew A. , Cho Nancy L. , Haase Jacob , Doherty Gerard M. , Sehgal Kartik , Barletta Justine A. , Alexander Erik K. , Landa Iñigo
Published: July 2023

Supplementary Table S2. Characteristics of patients with RAS-mutant anaplastic thyroid cancer
Supplementary Figure S5 from TIGIT Expression Delineates T-cell Populations with Distinct Functional and Prognostic Impact in Pancreatic Cancer
Authors: Heiduk Max , Klimova Anna , Reiche Charlotte , Digomann David , Beer Carolin , Aust Daniela E. , Distler Marius , Weitz Jürgen , Seifert Adrian M. , Seifert Lena
Published: July 2023

Representative flow plots of cytokine expression.
Supplementary Figure S3 from TIGIT Expression Delineates T-cell Populations with Distinct Functional and Prognostic Impact in Pancreatic Cancer
Authors: Heiduk Max , Klimova Anna , Reiche Charlotte , Digomann David , Beer Carolin , Aust Daniela E. , Distler Marius , Weitz Jürgen , Seifert Adrian M. , Seifert Lena
Published: July 2023

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

Survival analyses for PD-1 and TIGIT co-expression in blood.
Supplementary Figure S10 from TIGIT Expression Delineates T-cell Populations with Distinct Functional and Prognostic Impact in Pancreatic Cancer
Authors: Heiduk Max , Klimova Anna , Reiche Charlotte , Digomann David , Beer Carolin , Aust Daniela E. , Distler Marius , Weitz Jürgen , Seifert Adrian M. , Seifert Lena
Published: July 2023

Kaplan-Meier analyses for PD-1 and TIGIT co-expression in blood.
Supplementary Figure S1 from TIGIT Expression Delineates T-cell Populations with Distinct Functional and Prognostic Impact in Pancreatic Cancer
Authors: Heiduk Max , Klimova Anna , Reiche Charlotte , Digomann David , Beer Carolin , Aust Daniela E. , Distler Marius , Weitz Jürgen , Seifert Adrian M. , Seifert Lena
Published: July 2023

Gating strategy and correlation of PD-1 and TIGIT expression.
Supplementary Data 1 from Efficacy and Quality-of-Life Following Involved Nodal Radiotherapy for Head and Neck Squamous Cell Carcinoma: The INRT-AIR Phase II Clinical Trial
Authors: Sher David J. , Moon Dominic H. , Vo Dat , Wang Jing , Chen Liyuan , Dohopolski Michael , Hughes Randall , Sumer Baran D. , Ahn Chul , Avkshtol Vladimir
Published: July 2023

Includes Supp Figure 1, Supp Table 1 (representativeness table) and Supp Methods
Supplementary Table S2 from Safety and Efficacy of Tucatinib, Letrozole, and Palbociclib in Patients with Previously Treated HR+/HER2+ Breast Cancer
Authors: Shagisultanova Elena , Gradishar William , Brown-Glaberman Ursa , Chalasani Pavani , Brenner Andrew J. , Stopeck Alison , Parris Hannah , Gao Dexiang , McSpadden Tessa , Mayordomo Jose , Diamond Jennifer R. , Kabos Peter , Borges Virginia F.
Published: July 2023

Serious adverse events
Supplementary Fig. S3 from Safety and Efficacy of Tucatinib, Letrozole, and Palbociclib in Patients with Previously Treated HR+/HER2+ Breast Cancer
Authors: Shagisultanova Elena , Gradishar William , Brown-Glaberman Ursa , Chalasani Pavani , Brenner Andrew J. , Stopeck Alison , Parris Hannah , Gao Dexiang , McSpadden Tessa , Mayordomo Jose , Diamond Jennifer R. , Kabos Peter , Borges Virginia F.
Published: July 2023

PFS before and after palbociclib dose change
Supplementary Fig. S1 from Safety and Efficacy of Tucatinib, Letrozole, and Palbociclib in Patients with Previously Treated HR+/HER2+ Breast Cancer
Authors: Shagisultanova Elena , Gradishar William , Brown-Glaberman Ursa , Chalasani Pavani , Brenner Andrew J. , Stopeck Alison , Parris Hannah , Gao Dexiang , McSpadden Tessa , Mayordomo Jose , Diamond Jennifer R. , Kabos Peter , Borges Virginia F.
Published: July 2023

PK analysis
Supplementary Appendix 1 from Safety, Efficacy, and Biomarker Analyses of Dostarlimab in Patients with Endometrial Cancer: Interim Results of the Phase I GARNET Study
Authors: Oaknin Ana , Pothuri Bhavana , Gilbert Lucy , Sabatier Renaud , Brown Jubilee , Ghamande Sharad , Mathews Cara , O'Malley David M. , Kristeleit Rebecca , Boni Valentina , Gravina Adriano , Banerjee Susana , Miller Rowan , Pikiel Joanna , Mirza Mansoor R. , Dewal Ninad , Antony Grace , Dong Yuping , Zografos Eleftherios , Veneris Jennifer , Tinker Anna V.
Published: July 2023

This includes supplementary tables and figures
Supplementary Table S2 from Patient-Reported Outcomes as Interradiographic Predictors of Response in Non–Small Cell Lung Cancer
Authors: Bhatt Ambika S. , Schabath Matthew B. , Hoogland Aasha I. , Jim Heather S.L. , Brady-Nicholls Renee
Published: July 2023

Representativeness of study participants table
Supplemental Table 2 from The GENIE BPC NSCLC Cohort: A Real-World Repository Integrating Standardized Clinical and Genomic Data for 1,846 Patients with Non–Small Cell Lung Cancer
Authors: Choudhury Noura J. , Lavery Jessica A. , Brown Samantha , de Bruijn Ino , Jee Justin , Tran Thinh Ngoc , Rizvi Hira , Arbour Kathryn C. , Whiting Karissa , Shen Ronglai , Hellmann Matthew , Bedard Philippe L. , Yu Celeste , Leighl Natasha , LeNoue-Newton Michele , Micheel Christine , Warner Jeremy L. , Ginsberg Michelle S. , Plodkowski Andrew , Girshman Jeffrey , Sawan Peter , Pillai Shirin , Sweeney Shawn M. , Kehl Kenneth L. , Panageas Katherine S. , Schultz Nikolaus , Schrag Deborah , Riely Gregory J.
Published: July 2023

Supplemental Table 2
Supplemental Table 1 from The GENIE BPC NSCLC Cohort: A Real-World Repository Integrating Standardized Clinical and Genomic Data for 1,846 Patients with Non–Small Cell Lung Cancer
Authors: Choudhury Noura J. , Lavery Jessica A. , Brown Samantha , de Bruijn Ino , Jee Justin , Tran Thinh Ngoc , Rizvi Hira , Arbour Kathryn C. , Whiting Karissa , Shen Ronglai , Hellmann Matthew , Bedard Philippe L. , Yu Celeste , Leighl Natasha , LeNoue-Newton Michele , Micheel Christine , Warner Jeremy L. , Ginsberg Michelle S. , Plodkowski Andrew , Girshman Jeffrey , Sawan Peter , Pillai Shirin , Sweeney Shawn M. , Kehl Kenneth L. , Panageas Katherine S. , Schultz Nikolaus , Schrag Deborah , Riely Gregory J.
Published: July 2023

Supplemental Table 1
Supplemental Fig. 3 from The GENIE BPC NSCLC Cohort: A Real-World Repository Integrating Standardized Clinical and Genomic Data for 1,846 Patients with Non–Small Cell Lung Cancer
Authors: Choudhury Noura J. , Lavery Jessica A. , Brown Samantha , de Bruijn Ino , Jee Justin , Tran Thinh Ngoc , Rizvi Hira , Arbour Kathryn C. , Whiting Karissa , Shen Ronglai , Hellmann Matthew , Bedard Philippe L. , Yu Celeste , Leighl Natasha , LeNoue-Newton Michele , Micheel Christine , Warner Jeremy L. , Ginsberg Michelle S. , Plodkowski Andrew , Girshman Jeffrey , Sawan Peter , Pillai Shirin , Sweeney Shawn M. , Kehl Kenneth L. , Panageas Katherine S. , Schultz Nikolaus , Schrag Deborah , Riely Gregory J.
Published: July 2023

Supplemental Figure 3: PFS estimates for patients with NSCLC treated with standard first- and second-line therapies.
Supplementary Table 1 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: July 2023

Supplementary Table
Data from ALK Amplification and Rearrangements Are Recurrent Targetable Events in Congenital and Adult Glioblastoma
Authors: Blandin Anne-Florence , Giglio Ross , Graham Maya Srikanth , Garcia Guadalupe , Malinowski Seth , Woods Jared K. , Ramkissoon Shakti , Ramkissoon Lori , Dubois Frank , Schoolcraft Kathleen , Tsai Jessica , Wang Dayle , Jones Robert , Vogelzang Jayne , Pelton Kristine , Becker Sarah , Watkinson Fiona , Sinai Claire , Cohen Elizabeth F. , Booker Matthew A. , Tolstorukov Michael Y. , Haemels Veerle , Goumnerova Liliana , Wright Karen , Kieran Mark , Fehnel Katie , Reardon David , Tauziede-Espariat Arnault , Lulla Rishi , Carcamo Benjamin , Chaleff Stanley , Charest Alain , De Smet Frederik , Ligon Azra H. , Dubuc Adrian , Pages Melanie , Varlet Pascale , Wen Patrick Y. , Alexander Brian M. , Chi Susan , Alexandrescu Sanda , Kittler Ralf , Bachoo Robert , Bandopadhayay Pratiti , Beroukhim Rameen , Ligon Keith L.
Published: July 2023

AbstractPurpose:
Anaplastic lymphoma kinase (ALK) aberrations have been identified in pediatric-type infant gliomas, but their occurrence across age groups, functional effects, and treatment response has not been broadly established.
Experimental Design:
We performed a comprehensive analysis of ALK expression and genomic aberrations in both newly generated and retrospective data from 371 glioblastomas (156 adult, 205 infant/pediatric, and 10 congenital) with in vitro and in vivo validation of aberrations.
Results:
ALK aberrations at the protein or genomic level were detected in 12% of gliomas (45/371) in a wide age range (0–80 years). Recurrent as well as novel ALK fusions (LRRFIP1–ALK, DCTN1–ALK, PRKD3–ALK) were present in 50% (5/10) of congenital/infant, 1.4% (3/205) of pediatric, and 1.9% (3/156) of adult GBMs. ALK fusions were present as the only candidate driver in congenital/infant GBMs and were sometimes focally amplified. In contrast, adult ALK fusions co-occurred with other oncogenic drivers. No activating ALK mutations were identified in any age group. Novel and recurrent ALK rearrangements promoted STAT3 and ERK1/2 pathways and transformation in vitro and in vivo. ALK-fused GBM cellular and mouse models were responsive to ALK inhibitors, including in patient cells derived from a congenital GBM. Relevant to the treatment of infant gliomas, we showed that ALK protein appears minimally expressed in the forebrain at perinatal stages, and no gross effects on perinatal brain development were seen in pregnant mice treated with the ALK inhibitor ceritinib.
Conclusions:
These findings support use of brain-penetrant ALK inhibitors in clinical trials across infant, pediatric, and adult GBMs.

See related commentary by Mack and Bertrand, p. 2567
Data from Monitoring Sarcoma Response to Immune Checkpoint Inhibition and Local Cryotherapy with Circulating Tumor DNA Analysis
Authors: Bui Nam Q. , Nemat-Gorgani Neda , Subramanian Ajay , Torres Ileana A. , Lohman Marta , Sears Timothy J. , van de Rijn Matt , Charville Gregory W. , Becker Hans-Christoph , Wang David S. , Hwang Gloria L. , Ganjoo Kristen N. , Moding Everett J.
Published: July 2023

AbstractPurpose:
Immune checkpoint inhibition has led to promising responses in soft tissue sarcomas (STS), but the majority of patients do not respond and biomarkers of response will be crucial. Local ablative therapies may augment systemic responses to immunotherapy. We evaluated circulating tumor DNA (ctDNA) as a biomarker of response in patients treated on a trial combining immunotherapy with local cryotherapy for advanced STS.
Patients and Methods:
We enrolled 30 patients with unresectable or metastatic STS to a phase II clinical trial. Patients received ipilimumab and nivolumab for four doses followed by nivolumab alone with cryoablation performed between cycles 1 and 2. The primary endpoint was objective response rate (ORR) by 14 weeks. Personalized ctDNA analysis using bespoke panels was performed on blood samples collected prior to each immunotherapy cycle.
Results:
ctDNA was detected in at least one sample for 96% of patients. Pretreatment ctDNA allele fraction was negatively associated with treatment response, progression-free survival (PFS), and overall survival (OS). ctDNA increased in 90% of patients from pretreatment to postcryotherapy, and patients with a subsequent decrease in ctDNA or undetectable ctDNA after cryotherapy had significantly better PFS. Of the 27 evaluable patients, the ORR was 4% by RECIST and 11% by irRECIST. Median PFS and OS were 2.7 and 12.0 months, respectively. No new safety signals were observed.
Conclusions:
ctDNA represents a promising biomarker for monitoring response to treatment in patients with advanced STS, warranting future prospective studies. Combining cryotherapy and immune checkpoint inhibitors did not increase the response rate of STS to immunotherapy.
Data from Outcomes in Patients with High-Risk Features after Fixed-Duration Ibrutinib plus Venetoclax: Phase II CAPTIVATE Study in First-Line Chronic Lymphocytic Leukemia
Authors: Allan John N. , Flinn Ian W. , Siddiqi Tanya , Ghia Paolo , Tam Constantine S. , Kipps Thomas J. , Barr Paul M. , Elinder Camburn Anna , Tedeschi Alessandra , Badoux Xavier C. , Jacobs Ryan , Kuss Bryone J. , Trentin Livio , Zhou Cathy , Szoke Anita , Abbazio Christopher , Wierda William G.
Published: July 2023

AbstractPurpose:
The CAPTIVATE study investigated first-line ibrutinib plus venetoclax for chronic lymphocytic leukemia in 2 cohorts: minimal residual disease (MRD)-guided randomized discontinuation (MRD cohort) and Fixed Duration (FD cohort). We report outcomes of fixed-duration ibrutinib plus venetoclax in patients with high-risk genomic features [del(17p), TP53 mutation, and/or unmutated immunoglobulin heavy chain (IGHV)] in CAPTIVATE.
Patients and Methods:
Patients received three cycles of ibrutinib 420 mg/day then 12 cycles of ibrutinib plus venetoclax (5-week ramp-up to 400 mg/day). FD cohort patients (n = 159) received no further treatment. Forty-three MRD cohort patients with confirmed undetectable MRD (uMRD) after 12 cycles of ibrutinib plus venetoclax received randomized placebo treatment.
Results:
Of 195 patients with known status of genomic risk features at baseline, 129 (66%) had ≥1 high-risk feature. Overall response rates were >95% regardless of high-risk features. In patients with and without high-risk features, respectively, complete response (CR) rates were 61% and 53%; best uMRD rates: 88% and 70% (peripheral blood) and 72% and 61% (bone marrow); 36-month progression-free survival (PFS) rates: 88% and 92%. In subsets with del(17p)/TP53 mutation (n = 29) and unmutated IGHV without del(17p)/TP53 mutation (n = 100), respectively, CR rates were 52% and 64%; uMRD rates: 83% and 90% (peripheral blood) and 45% and 80% (bone marrow); 36-month PFS rates: 81% and 90%. Thirty-six–month overall survival (OS) rates were >95% regardless of high-risk features.
Conclusions:
Deep, durable responses and sustained PFS seen with fixed-duration ibrutinib plus venetoclax are maintained in patients with high-risk genomic features, with similar PFS and OS to those without high-risk features.

See related commentary by Rogers, p. 2561
Data from The Impact of Germline Alterations in Appendiceal Adenocarcinoma
Authors: Foote Michael B. , Walch Henry , Kemel Yelena , Vakiani Efsevia , Johannet Paul , Sheehan Margaret , Chatila Walid , Chung Sebastian , Nash Garrett M. , Maio Anna , Shia Jinru , Mandelker Diana , Berger Michael , Schultz Nikolaus , Diaz Luis A. , Cercek Andrea , Stadler Zsofia K.
Published: July 2023

AbstractPurpose:
More than 10% of assessed patients with appendiceal adenocarcinoma have a pathogenic (P) or likely pathogenic (LP) germline variant, including genes implicated in heritable gastrointestinal cancer syndromes, such as Lynch syndrome. We defined the clinical and molecular impact of heritable alterations in appendiceal adenocarcinoma to evaluate the need for dedicated appendiceal screening and prevention strategies in patients with LP/P germline variants.
Experimental Design:
We performed an integrated germline and somatic molecular analysis for patients with confirmed appendiceal adenocarcinoma. Patients underwent paired tumor-normal sequencing for up to 90 hereditary cancer risk genes and 505 genes for somatic mutation profiling. We defined the cooccurrence of LP/P germline variants and second-hit pathogenic somatic alterations. The associations between germline variants and patient clinicopathologic features were also evaluated.
Results:
Twenty-five of 237 patients (10.5%) carried pathogenic or likely pathogenic germline variants in cancer susceptibility genes. Clinicopathologic characteristics and appendiceal adenocarcinoma–specific survival were similar in patients with or without germline variants. Most (92%, N = 23/25) patients with germline variants demonstrated no second-hit somatic alterations, including loss of heterozygosity. Two patients with a germline APC I1307K low-penetrance founder variant exhibited secondary somatic pathogenic alterations in APC. However, only one patient tumor exhibited APC-mediated WNT signaling dysregulation: a plausible consequence of multiple somatic APC mutations with no germline variant contribution. Four patients had germline variants in PMS2 or MSH2 associated with Lynch syndrome, yet their cancers were microsatellite-stable.
Conclusions:
Germline variants are likely incidental without a contributory driver role in appendiceal adenocarcinoma. Appendiceal adenocarcinoma screening in patients with germline variants is not clearly merited.
Data from Plasma 25-Hydroxyvitamin D Levels and Survival in Stage III Colon Cancer: Findings from CALGB/SWOG 80702 (Alliance)
Authors: Wang Qiao-Li , Ma Chao , Yuan Chen , Shi Qian , Wolpin Brian M. , Zhang Yin , Fuchs Charles S. , Meyer Jeffrey , Zemla Tyler , Cheng En , Kumthekar Priya , Guthrie Katherine A. , Couture Felix , Kuebler Philip , Kumar Pankaj , Tan Benjamin , Krishnamurthi Smitha , Goldberg Richard M. , Venook Alan , Blanke Charles , Shields Anthony F. , O'Reilly Eileen M. , Meyerhardt Jeffrey A. , Ng Kimmie
Published: July 2023

AbstractPurpose:
To assess whether higher plasma 25-hydroxyvitamin D [25(OH)D] is associated with improved outcomes in colon cancer and whether circulating inflammatory cytokines mediate such association.
Experimental Design:
Plasma samples were collected from 1,437 patients with stage III colon cancer enrolled in a phase III randomized clinical trial (CALGB/SWOG 80702) from 2010 to 2015, who were followed until 2020. Cox regressions were used to examine associations between plasma 25(OH)D and disease-free survival (DFS), overall survival (OS), and time to recurrence (TTR). Mediation analysis was performed for circulating inflammatory biomarkers of C-reactive protein (CRP), IL6, and soluble TNF receptor 2 (sTNF-R2).
Results:
Vitamin D deficiency [25(OH)D <12 ng/mL] was present in 13% of total patients at baseline and in 32% of Black patients. Compared with deficiency, nondeficient vitamin D status (≥12 ng/mL) was significantly associated with improved DFS, OS, and TTR (all Plog-rank<0.05), with multivariable-adjusted HRs of 0.68 (95% confidence interval, 0.51–0.92) for DFS, 0.57 (0.40–0.80) for OS, and 0.71 (0.52–0.98) for TTR. A U-shaped dose–response pattern was observed for DFS and OS (both Pnonlinearity<0.05). The proportion of the association with survival that was mediated by sTNF-R2 was 10.6% (Pmediation = 0.04) for DFS and 11.8% (Pmediation = 0.05) for OS, whereas CRP and IL6 were not shown to be mediators. Plasma 25(OH)D was not associated with the occurrence of ≥ grade 2 adverse events.
Conclusions:
Nondeficient vitamin D is associated with improved outcomes in patients with stage III colon cancer, largely independent of circulation inflammations. A randomized trial is warranted to elucidate whether adjuvant vitamin D supplementation improves patient outcomes.
Data 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: July 2023

AbstractPurpose:
Relapsed T-acute lymphoblastic leukemia (T-ALL) has limited treatment options. We investigated mechanisms of resistance to BH3 mimetics in T-ALL to develop rational combination strategies. We also looked at the preclinical efficacy of NWP-0476, a novel BCL-2/BCL-xL inhibitor, as single agent and combination therapy in T-ALL.
Methods:
We used BH3 profiling as a predictive tool for BH3 mimetic response in T-ALL. Using isogenic control, venetoclax-resistant (ven-R) and NWP-0476-resistant (NWP-R) cells, phosphokinase array was performed to identify differentially regulated signaling pathways.
Results:
Typical T-ALL cells had increased dependence on BCL-xL, whereas early T-precursor (ETP)-ALL cells had higher BCL-2 dependence for survival. BCL-2/BCL-xL dual inhibitors were effective against both subtypes of T-lineage ALL. A 71-protein human phosphokinase array showed increased LCK activity in ven-R cells, and increased ACK1 activity in ven-R and NWP-R cells. We hypothesized that pre-TCR and ACK1 signaling pathways are drivers of resistance to BCL-2 and BCL-xL inhibition, respectively. First, we silenced LCK gene in T-ALL cell lines, which resulted in increased sensitivity to BCL-2 inhibition. Mechanistically, LCK activated NF-κB pathway and the expression of BCL-xL. Silencing ACK1 gene resulted in increased sensitivity to both BCL-2 and BCL-xL inhibitors. ACK1 signaling upregulated AKT pathway, which inhibited the pro-apoptotic function of BAD. In a T-ALL patient-derived xenograft model, combination of NWP-0476 and dasatinib demonstrated synergy without major organ toxicity.
Conclusions:
LCK and ACK1 signaling pathways are critical regulators of BH3 mimetic resistance in T-ALL. Combination of BH3 mimetics with tyrosine kinase inhibitors might be effective against relapsed T-ALL.