bluuebunny/crossref_metadata_2025 huggingface dataset:
Data from Using DEPendency of Association on the Number of Top Hits (DEPTH) as a Complementary Tool to Identify Novel Colorectal Cancer Susceptibility Loci
Authors: Lai John , Wong Chi Kuen , Schmidt Daniel F. , Kapuscinski Miroslaw K. , Alpen Karen , MacInnis Robert J. , Buchanan Daniel D. , Win Aung K. , Figueiredo Jane C. , Chan Andrew T. , Harrison Tabitha A. , Hoffmeister Michael , White Emily , Le Marchand Loic , Pai Rish K. , Peters Ulrike , Hopper John L. , Jenkins Mark A. , Makalic Enes
Published: September 2023

AbstractBackground:
DEPendency of association on the number of Top Hits (DEPTH) is an approach to identify candidate susceptibility regions by considering the risk signals from overlapping groups of sequential variants across the genome.
Methods:
We applied a DEPTH analysis using a sliding window of 200 SNPs to colorectal cancer data from the Colon Cancer Family Registry (CCFR; 5,735 cases and 3,688 controls), and Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO; 8,865 cases and 10,285 controls) studies. A DEPTH score > 1 was used to identify candidate susceptibility regions common to both analyses. We compared DEPTH results against those from conventional genome-wide association study (GWAS) analyses of these two studies as well as against 132 published susceptibility regions.
Results:
Initial DEPTH analysis revealed 2,622 (CCFR) and 3,686 (GECCO) candidate susceptibility regions, of which 569 were common to both studies. Bootstrapping revealed 40 and 49 candidate susceptibility regions in the CCFR and GECCO data sets, respectively. Notably, DEPTH identified at least 82 regions that would not be detected using conventional GWAS methods, nor had they been identified by previous colorectal cancer GWASs. We found four reproducible candidate susceptibility regions (2q22.2, 2q33.1, 6p21.32, 13q14.3). The highest DEPTH scores were in the human leukocyte antigen locus at 6p21 where the strongest associated SNPs were rs762216297, rs149490268, rs114741460, and rs199707618 for the CCFR data, and rs9270761 for the GECCO data.
Conclusions:
DEPTH can identify candidate susceptibility regions for colorectal cancer not identified using conventional analyses of larger datasets.
Impact:
DEPTH has potential as a powerful complementary tool to conventional GWAS analyses for discovering susceptibility regions within the genome.
Data from Hospitalizations and Cost of Inpatient Care for Physical Diseases in Survivors of Childhood Cancer in Western Australia: A Longitudinal Matched Cohort Study
Authors: Abdalla Tasnim , Walwyn Thomas , White Daniel , Choong Catherine S. , Bulsara Max , Preen David B. , Ohan Jeneva L.
Published: September 2023

AbstractBackground:
The long-term effects of childhood cancer are unclear in the Australian context. We examined hospitalization trends for physical diseases and estimated the associated inpatient care costs in all 5-year childhood cancer survivors (CCS) diagnosed in Western Australia (WA) from 1982 to 2014.
Methods:
Hospitalization records for 2,938 CCS and 24,792 comparisons were extracted from 1987 to 2019 (median follow-up = 12 years, min = 1, max = 32). The adjusted hazard ratio (aHR) of hospitalization with 95% confidence intervals (CI) was estimated using the Andersen–Gill model for recurrent events. The cumulative burden of hospitalizations over time was assessed using the mean cumulative count method. The adjusted mean cost of hospitalization was estimated using the generalized linear models.
Results:
We identified a higher risk of hospitalization for all-cause (aHR, 2.0; 95% CI, 1.8–2.2) physical disease in CCS than comparisons, with the highest risk for subsequent malignant neoplasms (aHR, 15.0; 95% CI, 11.3–19.8) and blood diseases (aHR, 6.9; 95% CI, 2.6–18.2). Characteristics associated with higher hospitalization rates included female gender, diagnosis with bone tumors, cancer diagnosis age between 5 and 9 years, multiple childhood cancer diagnoses, multiple comorbidities, higher deprivation, increased remoteness, and Indigenous status. The difference in the mean total hospitalization costs for any disease was significantly higher in survivors than comparisons (publicly funded $11,483 United States Dollar, P < 0.05).
Conclusions:
The CCS population faces a significantly higher risk of physical morbidity and higher cost of hospital-based care than the comparisons.
Impact:
Our study highlights the need for long-term follow-up healthcare services to prevent disease progression and mitigate the burden of physical morbidity on CCS and hospital services.
Data from Characteristics of Cancer Epidemiology Studies That Employ Metabolomics: A Scoping Review
Authors: Yu Catherine T. , Farhat Zeinab , Livinski Alicia A. , Loftfield Erikka , Zanetti Krista A.
Published: September 2023

Abstract
An increasing number of cancer epidemiology studies use metabolomics assays. This scoping review characterizes trends in the literature in terms of study design, population characteristics, and metabolomics approaches and identifies opportunities for future growth and improvement. We searched PubMed/MEDLINE, Embase, Scopus, and Web of Science: Core Collection databases and included research articles that used metabolomics to primarily study cancer, contained a minimum of 100 cases in each main analysis stratum, used an epidemiologic study design, and were published in English from 1998 to June 2021. A total of 2,048 articles were screened, of which 314 full texts were further assessed resulting in 77 included articles. The most well-studied cancers were colorectal (19.5%), prostate (19.5%), and breast (19.5%). Most studies used a nested case–control design to estimate associations between individual metabolites and cancer risk and a liquid chromatography–tandem mass spectrometry untargeted or semi-targeted approach to measure metabolites in blood. Studies were geographically diverse, including countries in Asia, Europe, and North America; 27.3% of studies reported on participant race, the majority reporting White participants. Most studies (70.2%) included fewer than 300 cancer cases in their main analysis. This scoping review identified key areas for improvement, including needs for standardized race and ethnicity reporting, more diverse study populations, and larger studies.
Supplementary Tables 1-3 from De Novo and Histologically Transformed Small-Cell Lung Cancer Is Sensitive to Lurbinectedin Treatment Through the Modulation of EMT and NOTCH Signaling Pathways
Authors: Chakraborty Subhamoy , Coleman Charles , Manoj Parvathy , Demircioglu Deniz , Shah Nisargbhai , de Stanchina Elisa , Rudin Charles M. , Hasson Dan , Sen Triparna
Published: September 2023

Supplementary Tables 1-3
Figure S3 from De Novo and Histologically Transformed Small-Cell Lung Cancer Is Sensitive to Lurbinectedin Treatment Through the Modulation of EMT and NOTCH Signaling Pathways
Authors: Chakraborty Subhamoy , Coleman Charles , Manoj Parvathy , Demircioglu Deniz , Shah Nisargbhai , de Stanchina Elisa , Rudin Charles M. , Hasson Dan , Sen Triparna
Published: September 2023

Figure S3: Lurbinectedin treatment induces regulators of the DNA damage response pathway.
Figure S1 from De Novo and Histologically Transformed Small-Cell Lung Cancer Is Sensitive to Lurbinectedin Treatment Through the Modulation of EMT and NOTCH Signaling Pathways
Authors: Chakraborty Subhamoy , Coleman Charles , Manoj Parvathy , Demircioglu Deniz , Shah Nisargbhai , de Stanchina Elisa , Rudin Charles M. , Hasson Dan , Sen Triparna
Published: September 2023

Figure S1. Lurbinectedin decreases cell viability in a time and dose-dependent manner.
Supplementary Table S5 from Phase I trial of Ganitumab plus Dasatinib to Cotarget the Insulin-Like Growth Factor 1 Receptor and Src Family Kinase YES in Rhabdomyosarcoma
Authors: Akshintala Srivandana , Sundby R. Taylor , Bernstein Donna , Glod John W. , Kaplan Rosandra N. , Yohe Marielle E. , Gross Andrea M. , Derdak Joanne , Lei Haiyan , Pan Alexander , Dombi Eva , Palacio-Yance Isabel , Herrera Kailey R. , Miettinen Markku M. , Chen Helen X. , Steinberg Seth M. , Helman Lee J. , Mascarenhas Leo , Widemann Brigitte C. , Navid Fariba , Shern Jack F. , Heske Christine M.
Published: September 2023

Summary statistics for nucleosome footprints at YES1 and IGF1R regulatory motifs
Supplementary Table S4 from Phase I trial of Ganitumab plus Dasatinib to Cotarget the Insulin-Like Growth Factor 1 Receptor and Src Family Kinase YES in Rhabdomyosarcoma
Authors: Akshintala Srivandana , Sundby R. Taylor , Bernstein Donna , Glod John W. , Kaplan Rosandra N. , Yohe Marielle E. , Gross Andrea M. , Derdak Joanne , Lei Haiyan , Pan Alexander , Dombi Eva , Palacio-Yance Isabel , Herrera Kailey R. , Miettinen Markku M. , Chen Helen X. , Steinberg Seth M. , Helman Lee J. , Mascarenhas Leo , Widemann Brigitte C. , Navid Fariba , Shern Jack F. , Heske Christine M.
Published: September 2023

Tumor fractions from plasma cfDNA.
Supplementary Figure S3 from A Bifunctional PARP-HDAC Inhibitor with Activity in Ewing Sarcoma
Authors: Ramos Louise , Truong Sarah , Zhai Beibei , Joshi Jay , Ghaidi Fariba , Lizardo Michael M. , Shyp Taras , Kung Sonia H.Y. , Rezakhanlou Alireza M. , Oo Htoo Zarni , Adomat Hans , Le Bihan Stephane , Collins Colin , Bacha Jeffrey , Brown Dennis , Langlands John , Shen Wang , Lallous Nada , Sorensen Poul H. , Daugaard Mads
Published: September 2023

Replicates of cell cycle assays and statistics
Supplementary Figure S2 from A Bifunctional PARP-HDAC Inhibitor with Activity in Ewing Sarcoma
Authors: Ramos Louise , Truong Sarah , Zhai Beibei , Joshi Jay , Ghaidi Fariba , Lizardo Michael M. , Shyp Taras , Kung Sonia H.Y. , Rezakhanlou Alireza M. , Oo Htoo Zarni , Adomat Hans , Le Bihan Stephane , Collins Colin , Bacha Jeffrey , Brown Dennis , Langlands John , Shen Wang , Lallous Nada , Sorensen Poul H. , Daugaard Mads
Published: September 2023

Replicate graphs of cell viability assays and comparison of cell viability assay methods
Supplementary Table S1 from Phase I trial of Ganitumab plus Dasatinib to Cotarget the Insulin-Like Growth Factor 1 Receptor and Src Family Kinase YES in Rhabdomyosarcoma
Authors: Akshintala Srivandana , Sundby R. Taylor , Bernstein Donna , Glod John W. , Kaplan Rosandra N. , Yohe Marielle E. , Gross Andrea M. , Derdak Joanne , Lei Haiyan , Pan Alexander , Dombi Eva , Palacio-Yance Isabel , Herrera Kailey R. , Miettinen Markku M. , Chen Helen X. , Steinberg Seth M. , Helman Lee J. , Mascarenhas Leo , Widemann Brigitte C. , Navid Fariba , Shern Jack F. , Heske Christine M.
Published: September 2023

Representativeness of Study Participants
Supplementary Figure S1 from A Bifunctional PARP-HDAC Inhibitor with Activity in Ewing Sarcoma
Authors: Ramos Louise , Truong Sarah , Zhai Beibei , Joshi Jay , Ghaidi Fariba , Lizardo Michael M. , Shyp Taras , Kung Sonia H.Y. , Rezakhanlou Alireza M. , Oo Htoo Zarni , Adomat Hans , Le Bihan Stephane , Collins Colin , Bacha Jeffrey , Brown Dennis , Langlands John , Shen Wang , Lallous Nada , Sorensen Poul H. , Daugaard Mads
Published: September 2023

Replicate graphs of HDAC, PARP1, PARP2 and PARylation assays
Supplementary Appendix S1 from Phase I trial of Ganitumab plus Dasatinib to Cotarget the Insulin-Like Growth Factor 1 Receptor and Src Family Kinase YES in Rhabdomyosarcoma
Authors: Akshintala Srivandana , Sundby R. Taylor , Bernstein Donna , Glod John W. , Kaplan Rosandra N. , Yohe Marielle E. , Gross Andrea M. , Derdak Joanne , Lei Haiyan , Pan Alexander , Dombi Eva , Palacio-Yance Isabel , Herrera Kailey R. , Miettinen Markku M. , Chen Helen X. , Steinberg Seth M. , Helman Lee J. , Mascarenhas Leo , Widemann Brigitte C. , Navid Fariba , Shern Jack F. , Heske Christine M.
Published: September 2023

Supplemental Protocol Information. A: Study Eligibility; B: Dasatinib dosing nomogram; C: Dasatinib dose modifications
Supplementary Table S3 from Activin A–Mediated Polarization of Cancer-Associated Fibroblasts and Macrophages Confers Resistance to Checkpoint Immunotherapy in Skin Cancer
Authors: Pich-Bavastro Christine , Yerly Laura , Di Domizio Jeremy , Tissot-Renaud Stéphanie , Gilliet Michel , Kuonen François
Published: September 2023

Supplementary Table S3. Cluster marker genes of the Fibroblast populations.
Supplementary Figure S9 from Activin A–Mediated Polarization of Cancer-Associated Fibroblasts and Macrophages Confers Resistance to Checkpoint Immunotherapy in Skin Cancer
Authors: Pich-Bavastro Christine , Yerly Laura , Di Domizio Jeremy , Tissot-Renaud Stéphanie , Gilliet Michel , Kuonen François
Published: September 2023

Supplementary Figure S9: Immunosuppressive, Activin A-exposed macrophages are found in both human SCC and melanomas.
Supplementary Figure S6 from Activin A–Mediated Polarization of Cancer-Associated Fibroblasts and Macrophages Confers Resistance to Checkpoint Immunotherapy in Skin Cancer
Authors: Pich-Bavastro Christine , Yerly Laura , Di Domizio Jeremy , Tissot-Renaud Stéphanie , Gilliet Michel , Kuonen François
Published: September 2023

Supplementary Figure S6: Macrophages harbor different profiles in TME1 and TME2.
Supplementary Figure S4 from Activin A–Mediated Polarization of Cancer-Associated Fibroblasts and Macrophages Confers Resistance to Checkpoint Immunotherapy in Skin Cancer
Authors: Pich-Bavastro Christine , Yerly Laura , Di Domizio Jeremy , Tissot-Renaud Stéphanie , Gilliet Michel , Kuonen François
Published: September 2023

Supplementary Figure S4: Immunosuppressive, ECM-remodeling CAFs are found in both human SCC and melanomas.
Supplementary Figure S11 from Activin A–Mediated Polarization of Cancer-Associated Fibroblasts and Macrophages Confers Resistance to Checkpoint Immunotherapy in Skin Cancer
Authors: Pich-Bavastro Christine , Yerly Laura , Di Domizio Jeremy , Tissot-Renaud Stéphanie , Gilliet Michel , Kuonen François
Published: September 2023

Supplementary Figure S11: ICI-resistant BCCs harbor higher levels of TME2-like CAFs and myeloid cells.
Supplementary Figure S10 from Activin A–Mediated Polarization of Cancer-Associated Fibroblasts and Macrophages Confers Resistance to Checkpoint Immunotherapy in Skin Cancer
Authors: Pich-Bavastro Christine , Yerly Laura , Di Domizio Jeremy , Tissot-Renaud Stéphanie , Gilliet Michel , Kuonen François
Published: September 2023

Supplementary Figure S10: Unsupervised clustering of secretome gene expression reflects Macrophage subpopulations.
Supplementary Video S2B from First-in-Human Study of the Radioligand 68Ga-N188 Targeting Nectin-4 for PET/CT Imaging of Advanced Urothelial Carcinoma
Authors: Duan Xiaojiang , Xia Lei , Zhang Zhuochen , Ren Yanan , Pomper Martin G. , Rowe Steven P. , Li Xuesong , Li Nan , Zhang Ning , Zhu Hua , Yang Zhi , Sheng Xinan , Yang Xing
Published: September 2023

40 min full dynamic Total-body PET imaging of Patient 8
Supplementary Video S1 from First-in-Human Study of the Radioligand 68Ga-N188 Targeting Nectin-4 for PET/CT Imaging of Advanced Urothelial Carcinoma
Authors: Duan Xiaojiang , Xia Lei , Zhang Zhuochen , Ren Yanan , Pomper Martin G. , Rowe Steven P. , Li Xuesong , Li Nan , Zhang Ning , Zhu Hua , Yang Zhi , Sheng Xinan , Yang Xing
Published: September 2023

40 min full dynamic Total-body PET imaging of healthy volunteers
Supplementary Table S4 from First-in-Human Study of the Radioligand 68Ga-N188 Targeting Nectin-4 for PET/CT Imaging of Advanced Urothelial Carcinoma
Authors: Duan Xiaojiang , Xia Lei , Zhang Zhuochen , Ren Yanan , Pomper Martin G. , Rowe Steven P. , Li Xuesong , Li Nan , Zhang Ning , Zhu Hua , Yang Zhi , Sheng Xinan , Yang Xing
Published: September 2023

68Ga-N188 normal-organ absorbed doses in male (μGy/MBq, mean ± SD).
Supplementary Table S1 from First-in-Human Study of the Radioligand 68Ga-N188 Targeting Nectin-4 for PET/CT Imaging of Advanced Urothelial Carcinoma
Authors: Duan Xiaojiang , Xia Lei , Zhang Zhuochen , Ren Yanan , Pomper Martin G. , Rowe Steven P. , Li Xuesong , Li Nan , Zhang Ning , Zhu Hua , Yang Zhi , Sheng Xinan , Yang Xing
Published: September 2023

Representativeness of study participants
Supplementary Figures S1-S15 from First-in-Human Study of the Radioligand 68Ga-N188 Targeting Nectin-4 for PET/CT Imaging of Advanced Urothelial Carcinoma
Authors: Duan Xiaojiang , Xia Lei , Zhang Zhuochen , Ren Yanan , Pomper Martin G. , Rowe Steven P. , Li Xuesong , Li Nan , Zhang Ning , Zhu Hua , Yang Zhi , Sheng Xinan , Yang Xing
Published: September 2023

Figure S1. Synthesis of N188. Figure S2. Mass spectrometry characterization of N188.Figure S3. SPR characterization of N188.Figure S4. Radio-HPLC characterization of 68Ga-N188.Figure S5. Stability of 68Ga-N188 in serum and normal saline. Figure S6. Synthesis of FITC-N188. Figure S7. Mass spectrometry characterization of FITC-N188. Figure S8. Blood routine safety test. Figure S9. Toxicity test of 68Ga-N188. Figure S10. Results of PET/CT dynamic imaging studies in one healthy subject. Figure S11. Pharmacokinetics of 68Ga-N188 in mouse blood. Figure. S12 68Ga-N188 PET/CT imaging with maximum intensity projection (MIP) reconstruction of 12 advanced UC patients with obtained pathological sections. Figure S13. Representative PET/CT images of a patient (No. 3) with advanced urothelial carcinoma. Figure. S14 Comparison of brain metastasis imaging of patient No. 4 using 68Ga-N188, 18F-FDG PET/CT and MRI. Figure. S15 Nectin-4 IHC staining in 12 mUC patients with pathological sections of primary focus.
Supplementary Table S1 from KIT and PDGFRA Mutations and Survival of Gastrointestinal Stromal Tumor Patients Treated with Adjuvant Imatinib in a Randomized Trial
Authors: Joensuu Heikki , Wardelmann Eva , Eriksson Mikael , Reichardt Annette , Hall Kirsten Sundby , Schütte Jochen , Cameron Silke , Hohenberger Peter , Sihto Harri , Jost Philipp J. , Lindner Lars H. , Bauer Sebastian , Nilsson Bengt , Kallio Raija , Pesonen Tommi , Reichardt Peter
Published: September 2023

Representativeness of Study Participants
Supplementary Figure S3 from KIT and PDGFRA Mutations and Survival of Gastrointestinal Stromal Tumor Patients Treated with Adjuvant Imatinib in a Randomized Trial
Authors: Joensuu Heikki , Wardelmann Eva , Eriksson Mikael , Reichardt Annette , Hall Kirsten Sundby , Schütte Jochen , Cameron Silke , Hohenberger Peter , Sihto Harri , Jost Philipp J. , Lindner Lars H. , Bauer Sebastian , Nilsson Bengt , Kallio Raija , Pesonen Tommi , Reichardt Peter
Published: September 2023

Kaplan-Meier estimates of recurrence-free survival (A, C, E) and overall survival (B, D, F) of patients with KIT exon 11 insertion or duplication mutation (A, B), patients with PDGFRA exon 18 D842V mutation (C, D), and patients with no detected KIT or PDGFRA mutation (E, F). The 5-year and 10-year survival rates are shown. Censored patients are indicated with a bar.
Supplementary Data 1 from A Phase Ib, Open-label Study Evaluating the Safety and Efficacy of Ipatasertib plus Rucaparib in Patients with Metastatic Castration-resistant Prostate Cancer
Authors: Pook David , Geynisman Daniel M. , Carles Joan , de Braud Filippo , Joshua Anthony M. , Pérez-Gracia José Luis , Llácer Pérez Casilda , Shin Sang Joon , Fang Bruno , Barve Minal , Maruzzo Marco , Bracarda Sergio , Kim Miso , Kerloeguen Yannick , Gallo Jorge Daniel , Maund Sophia L. , Harris Adam , Huang Kuan-Chieh , Poon Victor , Sutaria Dhruvitkumar S. , Gurney Howard
Published: September 2023

Supplement Figure 1 and Table
Supplementary Table S1 from Early Clearance of Plasma Epidermal Growth Factor Receptor Mutations as a Predictor of Outcome on Osimertinib in Advanced Non–Small Cell Lung Cancer; Exploratory Analysis from AURA3 and FLAURA
Authors: Gray Jhanelle E. , Ahn Myung-Ju , Oxnard Geoffrey R. , Shepherd Frances A. , Imamura Fumio , Cheng Ying , Okamoto Isamu , Cho Byoung Chul , Lin Meng-Chih , Wu Yi-Long , Majem Margarita , Gautschi Oliver , Boyer Michael , Bulusu Krishna C. , Markovets Aleksandra , Barrett J. Carl , Hodge Rachel , McKeown Astrid , Hartmaier Ryan J. , Chmielecki Juliann , Papadimitrakopoulou Vassiliki A. , Ramalingam Suresh S.
Published: September 2023

Representativeness of study participants
Supplementary Figure S3 from Early Clearance of Plasma Epidermal Growth Factor Receptor Mutations as a Predictor of Outcome on Osimertinib in Advanced Non–Small Cell Lung Cancer; Exploratory Analysis from AURA3 and FLAURA
Authors: Gray Jhanelle E. , Ahn Myung-Ju , Oxnard Geoffrey R. , Shepherd Frances A. , Imamura Fumio , Cheng Ying , Okamoto Isamu , Cho Byoung Chul , Lin Meng-Chih , Wu Yi-Long , Majem Margarita , Gautschi Oliver , Boyer Michael , Bulusu Krishna C. , Markovets Aleksandra , Barrett J. Carl , Hodge Rachel , McKeown Astrid , Hartmaier Ryan J. , Chmielecki Juliann , Papadimitrakopoulou Vassiliki A. , Ramalingam Suresh S.
Published: September 2023

Kaplan–Meier estimates showing OS in all trial patients with a valid baseline (detectable or non-detectable) plasma ctDNA result in A, patients from the AURA3 trial (n = 291) and B, patients from the FLAURA trial (n = 499). Censored data are indicated by tick marks. Abbreviations: CI, confidence interval; EGFRm, epidermal growth factor receptor mutation (ex19del or L858R); HR, hazard ratio; mOS, median overall survival; NC, not calculable.
Supplementary Figure S2 from Early Clearance of Plasma Epidermal Growth Factor Receptor Mutations as a Predictor of Outcome on Osimertinib in Advanced Non–Small Cell Lung Cancer; Exploratory Analysis from AURA3 and FLAURA
Authors: Gray Jhanelle E. , Ahn Myung-Ju , Oxnard Geoffrey R. , Shepherd Frances A. , Imamura Fumio , Cheng Ying , Okamoto Isamu , Cho Byoung Chul , Lin Meng-Chih , Wu Yi-Long , Majem Margarita , Gautschi Oliver , Boyer Michael , Bulusu Krishna C. , Markovets Aleksandra , Barrett J. Carl , Hodge Rachel , McKeown Astrid , Hartmaier Ryan J. , Chmielecki Juliann , Papadimitrakopoulou Vassiliki A. , Ramalingam Suresh S.
Published: September 2023

Correlation between EGFRm allelic fraction at baseline by ddPCR (Biodesix) and NGS (Guardant Health) analyses in A, patients from the AURA3 trial (n = 202) and B, patients from the FLAURA trial (n = 347). Abbreviations: ddPCR, droplet digital PCR; EGFRm, epidermal growth factor receptor mutation (ex19del or L858R); NGS, next-generation sequencing.
Supplementary Figure S4 from Thyroid Cancers Exhibit Oncogene-Enhanced Macropinocytosis that Is Restrained by IGF1R and Promote Albumin–Drug Conjugate Response
Authors: Hu Huiyu , Ng Thomas S.C. , Kang Mikyung , Scott Ella , Li Ran , Quintana Jeremy M. , Matvey Dylan , Vantaku Venkata R. , Weissleder Ralph , Parangi Sareh , Miller Miles A.
Published: September 2023

MAPK pathway kinase inhibitors show little effect on albumin uptake in non-tumor tissues, and lectin and dextran uptakes in tumor tissues
Supplementary Figure S1 from Early Clearance of Plasma Epidermal Growth Factor Receptor Mutations as a Predictor of Outcome on Osimertinib in Advanced Non–Small Cell Lung Cancer; Exploratory Analysis from AURA3 and FLAURA
Authors: Gray Jhanelle E. , Ahn Myung-Ju , Oxnard Geoffrey R. , Shepherd Frances A. , Imamura Fumio , Cheng Ying , Okamoto Isamu , Cho Byoung Chul , Lin Meng-Chih , Wu Yi-Long , Majem Margarita , Gautschi Oliver , Boyer Michael , Bulusu Krishna C. , Markovets Aleksandra , Barrett J. Carl , Hodge Rachel , McKeown Astrid , Hartmaier Ryan J. , Chmielecki Juliann , Papadimitrakopoulou Vassiliki A. , Ramalingam Suresh S.
Published: September 2023

AURA3 flow diagram for ctDNA analysis (n = 291). Clearance refers to non-detectable plasma EGFRm, where EGFRm was detectable at baseline. *There were 9 patients in the osimertinib arm and 1 patient in the platinum-pemetrexed arm without a valid ddPCR result at Weeks 3 and 6; these samples were excluded from the ctDNA clearance analysis. Abbreviations: ctDNA, circulating tumor DNA; EGFRm, epidermal growth factor receptor mutation (ex19del or L858R).
Supplementary Figure S3 from Thyroid Cancers Exhibit Oncogene-Enhanced Macropinocytosis that Is Restrained by IGF1R and Promote Albumin–Drug Conjugate Response
Authors: Hu Huiyu , Ng Thomas S.C. , Kang Mikyung , Scott Ella , Li Ran , Quintana Jeremy M. , Matvey Dylan , Vantaku Venkata R. , Weissleder Ralph , Parangi Sareh , Miller Miles A.
Published: September 2023

MAPK/ERK and PTEN/PI3K modulation of macropinocytosis and albumin uptake
Supplementary Figure S2 from Thyroid Cancers Exhibit Oncogene-Enhanced Macropinocytosis that Is Restrained by IGF1R and Promote Albumin–Drug Conjugate Response
Authors: Hu Huiyu , Ng Thomas S.C. , Kang Mikyung , Scott Ella , Li Ran , Quintana Jeremy M. , Matvey Dylan , Vantaku Venkata R. , Weissleder Ralph , Parangi Sareh , Miller Miles A.
Published: September 2023

Assessment of albumin-bound chemotherapy efficacy and toxicity
Supplementary Data 1 from Comparative Genomic Analysis of Pancreatic Acinar Cell Carcinoma (PACC) and Pancreatic Ductal Adenocarcinoma (PDAC) Unveils New Actionable Genomic Aberrations in PACC
Authors: Florou Vaia , Elliott Andrew , Bailey Matthew H. , Stone David , Affolter Kajsa , Soares Heloisa P. , Nevala-Plagemann Chris , Scaife Courtney , Walker Phillip , Korn W. Michael , Lou Emil , Shroff Rachna T. , Hosein Peter J. , Garrido-Laguna Ignacio
Published: September 2023

Supplementary table
Supplementary Figure S1 from Thyroid Cancers Exhibit Oncogene-Enhanced Macropinocytosis that Is Restrained by IGF1R and Promote Albumin–Drug Conjugate Response
Authors: Hu Huiyu , Ng Thomas S.C. , Kang Mikyung , Scott Ella , Li Ran , Quintana Jeremy M. , Matvey Dylan , Vantaku Venkata R. , Weissleder Ralph , Parangi Sareh , Miller Miles A.
Published: September 2023

Albumin uptake is dependent on macropinocytosis in ATC
Supplementary Data 1 from Clinical and Genomic Characteristics of Patients with Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Metastatic Breast Cancer Following Progression on Cyclin-Dependent Kinase 4 and 6 Inhibitors
Authors: Rao Xi , Chen Yongmei , Beyrer Julie , Nash Smyth Emily , Morato Guimaraes Claudia , Litchfield Lacey M. , Bowman Lee , Lawrence Garreth W. , Aggarwal Amit , Andre Fabrice
Published: September 2023

Supplementary material
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: September 2023

Supplemental Table 1
Supplementary Data 1 from Adjuvant Nivolumab versus Ipilimumab in Resected Stage III/IV Melanoma: 5-Year Efficacy and Biomarker Results from CheckMate 238
Authors: Larkin James , Del Vecchio Michele , Mandalá Mario , Gogas Helen , Arance Fernandez Ana M. , Dalle Stéphane , Cowey Charles Lance , Schenker Michael , Grob Jean-Jacques , Chiarion-Sileni Vanna , Marquez-Rodas Ivan , Butler Marcus O. , Di Giacomo Anna Maria , Middleton Mark R. , Lutzky Jose , de la Cruz-Merino Luis , Arenberger Petr , Atkinson Victoria , Hill Andrew G. , Fecher Leslie A. , Millward Michael , Nathan Paul D. , Khushalani Nikhil I. , Queirolo Paola , Ritchings Corey , Lobo Maurice , Askelson Margarita , Tang Hao , Dolfi Sonia , Ascierto Paolo A. , Weber Jeffrey
Published: September 2023

DATA SUPPLEMENT Adjuvant Nivolumab Versus Ipilimumab in Resected Stage III/IV Melanoma: 5-Year Efficacy and Biomarker Results From CheckMate 238
Supplemental Fig. 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: September 2023

Supplemental Figure 2: OS and PFS for patients with NSCLC treated with first-line platinum-based chemotherapy.
Supplementary Figures and Tables 1 from Treatment Response in First-Line Metastatic Pancreatic Ductal Adenocarcinoma Is Stratified By a Composite Index of Tumor Proliferation and CD8 T-Cell Infiltration
Authors: Beatty Gregory L. , Delman Devora , Yu Jiayi , Liu Mingen , Li Joey H. , Zhang Liti , Lee Jae W. , Chang Renee B. , Bahary Nathan , Kennedy Eugene P. , Wang-Gillam Andrea , Rossi Gabriela R. , Garrido-Laguna Ignacio
Published: September 2023

Supplementary Figures 1-5 and Supplementary Tables 1-2
Supplementary Data 1 from Treatment Response in First-Line Metastatic Pancreatic Ductal Adenocarcinoma Is Stratified By a Composite Index of Tumor Proliferation and CD8 T-Cell Infiltration
Authors: Beatty Gregory L. , Delman Devora , Yu Jiayi , Liu Mingen , Li Joey H. , Zhang Liti , Lee Jae W. , Chang Renee B. , Bahary Nathan , Kennedy Eugene P. , Wang-Gillam Andrea , Rossi Gabriela R. , Garrido-Laguna Ignacio
Published: September 2023

DEG Table for Pre vs Post (mRNAseq)
Supplementary Table S3 from CDK4/6-MEK Inhibition in MPNSTs Causes Plasma Cell Infiltration, Sensitization to PD-L1 Blockade, and Tumor Regression
Authors: Kohlmeyer Jordan L. , Lingo Joshua J. , Kaemmer Courtney A. , Scherer Amanda , Warrier Akshaya , Voigt Ellen , Raygoza Garay Juan A. , McGivney Gavin R. , Brockman Qierra R. , Tang Amy , Calizo Ana , Pollard Kai , Zhang Xiaochun , Hirbe Angela C. , Pratilas Christine A. , Leidinger Mariah , Breheny Patrick , Chimenti Michael S. , Sieren Jessica C. , Monga Varun , Tanas Munir R. , Meyerholz David K. , Darbro Benjamin W. , Dodd Rebecca D. , Quelle Dawn E.
Published: September 2023

Supplementary Table S3. Cluster of differentiation (CD) markers used to delineate immune cell populations after gating on CD45+ live cells.
Supplementary Tables 1-5 from Caveolin Gene Expression Predicts Clinical Outcomes for Early-Stage HER2-Negative Breast Cancer Treated with Paclitaxel-Based Chemotherapy in the GeparSepto Trial
Authors: Williams Terence M. , Schneeweiss Andreas , Jackisch Christian , Shen Changxian , Weber Karsten E. , Fasching Peter A. , Denkert Carsten , Furlanetto Jenny , Heinmöller Ernst , Schmatloch Sabine , Karn Thomas , Szeto Christopher W. , van Mackelenbergh Marion T. , Nekljudova Valentina , Stickeler Elmar , Soon-Shiong Patrick , Schem Christian , Mairinger Thomas , Müller Volkmar , Marme Frederik , Untch Michael , Loibl Sibylle
Published: September 2023

Supplementary Tables 1-5
Supplementary Figure S2 from Caveolin Gene Expression Predicts Clinical Outcomes for Early-Stage HER2-Negative Breast Cancer Treated with Paclitaxel-Based Chemotherapy in the GeparSepto Trial
Authors: Williams Terence M. , Schneeweiss Andreas , Jackisch Christian , Shen Changxian , Weber Karsten E. , Fasching Peter A. , Denkert Carsten , Furlanetto Jenny , Heinmöller Ernst , Schmatloch Sabine , Karn Thomas , Szeto Christopher W. , van Mackelenbergh Marion T. , Nekljudova Valentina , Stickeler Elmar , Soon-Shiong Patrick , Schem Christian , Mairinger Thomas , Müller Volkmar , Marme Frederik , Untch Michael , Loibl Sibylle
Published: September 2023

Supplementary Figure S2. CAV1 and CAV2 expression in breast cancer.
Supplementary Figure S7 from CDK4/6-MEK Inhibition in MPNSTs Causes Plasma Cell Infiltration, Sensitization to PD-L1 Blockade, and Tumor Regression
Authors: Kohlmeyer Jordan L. , Lingo Joshua J. , Kaemmer Courtney A. , Scherer Amanda , Warrier Akshaya , Voigt Ellen , Raygoza Garay Juan A. , McGivney Gavin R. , Brockman Qierra R. , Tang Amy , Calizo Ana , Pollard Kai , Zhang Xiaochun , Hirbe Angela C. , Pratilas Christine A. , Leidinger Mariah , Breheny Patrick , Chimenti Michael S. , Sieren Jessica C. , Monga Varun , Tanas Munir R. , Meyerholz David K. , Darbro Benjamin W. , Dodd Rebecca D. , Quelle Dawn E.
Published: September 2023

Supplementary Figure S7. Analyses of p-RB1, Ki67, and PD-L1 in combination therapy-sensitive and - resistant MPNSTs and PD-L1 in NF1 patient tumors.
Supplementary Figure S1 from Caveolin Gene Expression Predicts Clinical Outcomes for Early-Stage HER2-Negative Breast Cancer Treated with Paclitaxel-Based Chemotherapy in the GeparSepto Trial
Authors: Williams Terence M. , Schneeweiss Andreas , Jackisch Christian , Shen Changxian , Weber Karsten E. , Fasching Peter A. , Denkert Carsten , Furlanetto Jenny , Heinmöller Ernst , Schmatloch Sabine , Karn Thomas , Szeto Christopher W. , van Mackelenbergh Marion T. , Nekljudova Valentina , Stickeler Elmar , Soon-Shiong Patrick , Schem Christian , Mairinger Thomas , Müller Volkmar , Marme Frederik , Untch Michael , Loibl Sibylle
Published: September 2023

Supplementary Figure S1. CAV1 and CAV2 before (A, C) and after (B, D) transformation of the continuous expression values.
Supplementary Figure S4 from CDK4/6-MEK Inhibition in MPNSTs Causes Plasma Cell Infiltration, Sensitization to PD-L1 Blockade, and Tumor Regression
Authors: Kohlmeyer Jordan L. , Lingo Joshua J. , Kaemmer Courtney A. , Scherer Amanda , Warrier Akshaya , Voigt Ellen , Raygoza Garay Juan A. , McGivney Gavin R. , Brockman Qierra R. , Tang Amy , Calizo Ana , Pollard Kai , Zhang Xiaochun , Hirbe Angela C. , Pratilas Christine A. , Leidinger Mariah , Breheny Patrick , Chimenti Michael S. , Sieren Jessica C. , Monga Varun , Tanas Munir R. , Meyerholz David K. , Darbro Benjamin W. , Dodd Rebecca D. , Quelle Dawn E.
Published: September 2023

Supplementary Figure S4. Predicted immune cell composition of human PNFs, ANNUBPs, and MPNSTs based on CIBERSORT analyses.
Supplementary Table S4 from A Phase I/II Trial of HER2 Vaccine–Primed Autologous T-Cell Infusions in Patients with Treatment Refractory HER2–Overexpressing Breast Cancer
Authors: Disis Mary L. , Dang Yushe , Coveler Andrew L. , Childs Jennifer S. , Higgins Doreen M. , Liu Ying , Zhou Jing , Mackay Sean , Salazar Lupe G.
Published: September 2023

Immunologic parameters between pre-treatment and post T cell infusion in PR+SD and PD patients.
Supplementary Figures S1-S4 from The Prognostic Effect of Immune Cell Infiltration Depends on Molecular Subtype in Endometrioid Ovarian Carcinomas
Authors: Heinze Karolin , Cairns Evan S. , Thornton Shelby , Harris Bronwyn , Milne Katy , Grube Marcel , Meyer Charlotte , Karnezis Anthony N. , Fereday Sian , Garsed Dale W. , Leung Samuel C.Y. , Chiu Derek S. , Moubarak Malak , Harter Philipp , Heitz Florian , McAlpine Jessica N. , DeFazio Anna , Bowtell David D.L. , Goode Ellen L. , Pike Malcolm , Ramus Susan J. , Pearce C. Leigh , Staebler Annette , Köbel Martin , Kommoss Stefan , Talhouk Aline , Nelson Brad H. , Anglesio Michael S.
Published: September 2023

Supplementary Figures S1-S4
Supplementary Figure 2 from A Prognostic Model Based on Residual Cancer Burden and Tumor-Infiltrating Lymphocytes on Residual Disease after Neoadjuvant Therapy in HER2+ Breast Cancer
Authors: Miglietta Federica , Ragazzi Moira , Fernandes Bethania , Griguolo Gaia , Massa Davide , Girardi Fabio , Bottosso Michele , Bisagni Alessandra , Zarrilli Giovanni , Porra Francesca , Iannaccone Daniela , Dore Leocadia , Gaudio Mariangela , Santandrea Giacomo , Fassan Matteo , Lo Mele Marcello , De Sanctis Rita , Zambelli Alberto , Bisagni Giancarlo , Guarneri Valentina , Dieci Maria Vittoria
Published: September 2023

Supplementary Figure 2 – Association between baseline TILs and pCR in: 2a) the overall cohort and 2b) the cohort of patients receiving taxane-only neoadjuvant chemotherapy (plus anti-HER2 treatment).
Table S1 from Combined CDK4/6 and ERK1/2 Inhibition Enhances Antitumor Activity in NF1-Associated Plexiform Neurofibroma
Authors: Flint Alyssa C. , Mitchell Dana K. , Angus Steven P. , Smith Abbi E. , Bessler Waylan , Jiang Li , Mang Henry , Li Xiaohong , Lu Qingbo , Rodriguez Brooke , Sandusky George E. , Masters Andi R. , Zhang Chi , Dang Pengtao , Koenig Jenna , Johnson Gary L. , Shen Weihua , Liu Jiangang , Aggarwal Amit , Donoho Gregory P. , Willard Melinda D. , Bhagwat Shripad V. , Clapp D. Wade , Rhodes Steven D.
Published: September 2023

Gene set enrichment analysis of RAS signatures
Figure S8 from Combined CDK4/6 and ERK1/2 Inhibition Enhances Antitumor Activity in NF1-Associated Plexiform Neurofibroma
Authors: Flint Alyssa C. , Mitchell Dana K. , Angus Steven P. , Smith Abbi E. , Bessler Waylan , Jiang Li , Mang Henry , Li Xiaohong , Lu Qingbo , Rodriguez Brooke , Sandusky George E. , Masters Andi R. , Zhang Chi , Dang Pengtao , Koenig Jenna , Johnson Gary L. , Shen Weihua , Liu Jiangang , Aggarwal Amit , Donoho Gregory P. , Willard Melinda D. , Bhagwat Shripad V. , Clapp D. Wade , Rhodes Steven D.
Published: September 2023

Pharmacokinetic Evaluation of abemaciclib and LY3214996
Figure S7 from Combined CDK4/6 and ERK1/2 Inhibition Enhances Antitumor Activity in NF1-Associated Plexiform Neurofibroma
Authors: Flint Alyssa C. , Mitchell Dana K. , Angus Steven P. , Smith Abbi E. , Bessler Waylan , Jiang Li , Mang Henry , Li Xiaohong , Lu Qingbo , Rodriguez Brooke , Sandusky George E. , Masters Andi R. , Zhang Chi , Dang Pengtao , Koenig Jenna , Johnson Gary L. , Shen Weihua , Liu Jiangang , Aggarwal Amit , Donoho Gregory P. , Willard Melinda D. , Bhagwat Shripad V. , Clapp D. Wade , Rhodes Steven D.
Published: September 2023

DNSC Colony Forming Assay Matrix, ipNF05.5 Western Blots, and ipNF95.6 Western Blots
Figure S6 from Combined CDK4/6 and ERK1/2 Inhibition Enhances Antitumor Activity in NF1-Associated Plexiform Neurofibroma
Authors: Flint Alyssa C. , Mitchell Dana K. , Angus Steven P. , Smith Abbi E. , Bessler Waylan , Jiang Li , Mang Henry , Li Xiaohong , Lu Qingbo , Rodriguez Brooke , Sandusky George E. , Masters Andi R. , Zhang Chi , Dang Pengtao , Koenig Jenna , Johnson Gary L. , Shen Weihua , Liu Jiangang , Aggarwal Amit , Donoho Gregory P. , Willard Melinda D. , Bhagwat Shripad V. , Clapp D. Wade , Rhodes Steven D.
Published: September 2023

Caspase Glo 3/7 Assay
Figure S4 from Combined CDK4/6 and ERK1/2 Inhibition Enhances Antitumor Activity in NF1-Associated Plexiform Neurofibroma
Authors: Flint Alyssa C. , Mitchell Dana K. , Angus Steven P. , Smith Abbi E. , Bessler Waylan , Jiang Li , Mang Henry , Li Xiaohong , Lu Qingbo , Rodriguez Brooke , Sandusky George E. , Masters Andi R. , Zhang Chi , Dang Pengtao , Koenig Jenna , Johnson Gary L. , Shen Weihua , Liu Jiangang , Aggarwal Amit , Donoho Gregory P. , Willard Melinda D. , Bhagwat Shripad V. , Clapp D. Wade , Rhodes Steven D.
Published: September 2023

SPI1 Mouse and ETV4 Human IHC Cytonuclear Analysis
Figure S3 from Combined CDK4/6 and ERK1/2 Inhibition Enhances Antitumor Activity in NF1-Associated Plexiform Neurofibroma
Authors: Flint Alyssa C. , Mitchell Dana K. , Angus Steven P. , Smith Abbi E. , Bessler Waylan , Jiang Li , Mang Henry , Li Xiaohong , Lu Qingbo , Rodriguez Brooke , Sandusky George E. , Masters Andi R. , Zhang Chi , Dang Pengtao , Koenig Jenna , Johnson Gary L. , Shen Weihua , Liu Jiangang , Aggarwal Amit , Donoho Gregory P. , Willard Melinda D. , Bhagwat Shripad V. , Clapp D. Wade , Rhodes Steven D.
Published: September 2023

Hallmark E2F Targets Enrichment Plot and Top DEGs
Figure S2 from Combined CDK4/6 and ERK1/2 Inhibition Enhances Antitumor Activity in NF1-Associated Plexiform Neurofibroma
Authors: Flint Alyssa C. , Mitchell Dana K. , Angus Steven P. , Smith Abbi E. , Bessler Waylan , Jiang Li , Mang Henry , Li Xiaohong , Lu Qingbo , Rodriguez Brooke , Sandusky George E. , Masters Andi R. , Zhang Chi , Dang Pengtao , Koenig Jenna , Johnson Gary L. , Shen Weihua , Liu Jiangang , Aggarwal Amit , Donoho Gregory P. , Willard Melinda D. , Bhagwat Shripad V. , Clapp D. Wade , Rhodes Steven D.
Published: September 2023

Reactome G1 Phase Heatmap and Top DEGs
Figure S11 from Combined CDK4/6 and ERK1/2 Inhibition Enhances Antitumor Activity in NF1-Associated Plexiform Neurofibroma
Authors: Flint Alyssa C. , Mitchell Dana K. , Angus Steven P. , Smith Abbi E. , Bessler Waylan , Jiang Li , Mang Henry , Li Xiaohong , Lu Qingbo , Rodriguez Brooke , Sandusky George E. , Masters Andi R. , Zhang Chi , Dang Pengtao , Koenig Jenna , Johnson Gary L. , Shen Weihua , Liu Jiangang , Aggarwal Amit , Donoho Gregory P. , Willard Melinda D. , Bhagwat Shripad V. , Clapp D. Wade , Rhodes Steven D.
Published: September 2023

DEG Tables and Volcano Plots
Figure S1 from Combined CDK4/6 and ERK1/2 Inhibition Enhances Antitumor Activity in NF1-Associated Plexiform Neurofibroma
Authors: Flint Alyssa C. , Mitchell Dana K. , Angus Steven P. , Smith Abbi E. , Bessler Waylan , Jiang Li , Mang Henry , Li Xiaohong , Lu Qingbo , Rodriguez Brooke , Sandusky George E. , Masters Andi R. , Zhang Chi , Dang Pengtao , Koenig Jenna , Johnson Gary L. , Shen Weihua , Liu Jiangang , Aggarwal Amit , Donoho Gregory P. , Willard Melinda D. , Bhagwat Shripad V. , Clapp D. Wade , Rhodes Steven D.
Published: September 2023

Hallmark KRAS Pathway Heatmap and Top DEGs
Data from KIT and PDGFRA Mutations and Survival of Gastrointestinal Stromal Tumor Patients Treated with Adjuvant Imatinib in a Randomized Trial
Authors: Joensuu Heikki , Wardelmann Eva , Eriksson Mikael , Reichardt Annette , Hall Kirsten Sundby , Schütte Jochen , Cameron Silke , Hohenberger Peter , Sihto Harri , Jost Philipp J. , Lindner Lars H. , Bauer Sebastian , Nilsson Bengt , Kallio Raija , Pesonen Tommi , Reichardt Peter
Published: September 2023

AbstractPurpose:
Limited data are available about the influence of KIT and PDGFRA mutations on overall survival (OS) of patients with gastrointestinal stromal tumor (GIST) treated with adjuvant imatinib.
Patients and Methods:
The Scandinavian Sarcoma Group XVIII/AIO multicenter trial accrued 400 patients with a high risk for GIST recurrence after macroscopically complete surgery between February 4, 2004, and September 29, 2008. The patients received adjuvant imatinib 400 mg/day for either 1 year or 3 years based on random allocation. We analyzed using conventional sequencing KIT and PDGFRA mutations centrally from 341 (85%) patients who had localized, centrally confirmed GIST, and correlated the results with recurrence-free survival (RFS) and OS in exploratory analyses.
Results:
During a median follow-up time of 10 years, 164 RFS events and 76 deaths occurred. Most patients were re-treated with imatinib when GIST recurred. Patients with KIT exon 11 deletion or indel mutation treated with 3 years of adjuvant imatinib survived longer than patients treated for 1 year [10-year OS 86% versus 64%, respectively; HR, 0.34; 95% confidence interval (CI), 0.15–0.72; P = 0.007], and also had longer RFS (10-year RFS 47% versus 29%; HR, 0.48; 95% CI, 0.31–0.74; P < 0.001). Patients with KIT exon 9 mutation had unfavorable OS regardless of the duration of adjuvant imatinib.
Conclusions:
Compared with 1 year of imatinib, 3 years of adjuvant imatinib led to 66% reduction in the estimated risk of death and a high 10-year OS rate in the subset of patients with a KIT exon 11 deletion/indel mutation.
Data from Adjuvant Nivolumab versus Ipilimumab in Resected Stage III/IV Melanoma: 5-Year Efficacy and Biomarker Results from CheckMate 238
Authors: Larkin James , Del Vecchio Michele , Mandalá Mario , Gogas Helen , Arance Fernandez Ana M. , Dalle Stéphane , Cowey Charles Lance , Schenker Michael , Grob Jean-Jacques , Chiarion-Sileni Vanna , Marquez-Rodas Ivan , Butler Marcus O. , Di Giacomo Anna Maria , Middleton Mark R. , Lutzky Jose , de la Cruz-Merino Luis , Arenberger Petr , Atkinson Victoria , Hill Andrew G. , Fecher Leslie A. , Millward Michael , Nathan Paul D. , Khushalani Nikhil I. , Queirolo Paola , Ritchings Corey , Lobo Maurice , Askelson Margarita , Tang Hao , Dolfi Sonia , Ascierto Paolo A. , Weber Jeffrey
Published: September 2023

AbstractPurpose:
In the phase III CheckMate 238 study, adjuvant nivolumab significantly improved recurrence-free survival (RFS) and distant metastasis-free survival versus ipilimumab in patients with resected stage IIIB–C or stage IV melanoma, with benefit sustained at 4 years. We report updated 5-year efficacy and biomarker findings.
Patients and Methods:
Patients with resected stage IIIB–C/IV melanoma were stratified by stage and baseline programmed death cell ligand 1 (PD-L1) expression and received nivolumab 3 mg/kg every 2 weeks or ipilimumab 10 mg/kg every 3 weeks for four doses and then every 12 weeks, both intravenously for 1 year until disease recurrence, unacceptable toxicity, or withdrawal of consent. The primary endpoint was RFS.
Results:
At a minimum follow-up of 62 months, RFS with nivolumab remained superior to ipilimumab (HR = 0.72; 95% confidence interval, 0.60–0.86; 5-year rates of 50% vs. 39%). Five-year distant metastasis-free survival (DMFS) rates were 58% with nivolumab versus 51% with ipilimumab. Five-year overall survival (OS) rates were 76% with nivolumab and 72% with ipilimumab (75% data maturity: 228 of 302 planned events). Higher levels of tumor mutational burden (TMB), tumor PD-L1, intratumoral CD8+ T cells and IFNγ-associated gene expression signature, and lower levels of peripheral serum C-reactive protein were associated with improved RFS and OS with both nivolumab and ipilimumab, albeit with limited clinically meaningful predictive value.
Conclusions:
Nivolumab is a proven adjuvant treatment for resected melanoma at high risk of recurrence, with sustained, long-term improvement in RFS and DMFS compared with ipilimumab and high OS rates. Identification of additional biomarkers is needed to better predict treatment outcome.

See related commentary by Augustin and Luke, p. 3253
Data from Treatment Response in First-Line Metastatic Pancreatic Ductal Adenocarcinoma Is Stratified By a Composite Index of Tumor Proliferation and CD8 T-Cell Infiltration
Authors: Beatty Gregory L. , Delman Devora , Yu Jiayi , Liu Mingen , Li Joey H. , Zhang Liti , Lee Jae W. , Chang Renee B. , Bahary Nathan , Kennedy Eugene P. , Wang-Gillam Andrea , Rossi Gabriela R. , Garrido-Laguna Ignacio
Published: September 2023

AbstractPurpose:
Determinants of treatment outcomes to chemotherapy-based regimens in metastatic pancreatic ductal adenocarcinoma (PDA) remain ill-defined. Our aim was to examine tissue-based correlates of treatment response and resistance using matched baseline and on-treatment biopsies collected from patients with PDA treated in the first-line metastatic setting.
Experimental Design:
Patients with treatment-naïve metastatic PDA were enrolled in a Phase II trial (NCT02077881) investigating gemcitabine plus nab-paclitaxel in combination with indoximod, an orally administered small-molecule inhibitor of the IDO pathway. Baseline and on-treatment biopsies (week 8) of metastatic lesions (88% liver) were collected from a cohort of responders (N = 8) and non-responders (N = 8) based on RECIST v1.1 and examined by multiplex IHC and mRNA sequencing.
Results:
Treatment altered the transcriptional profile of metastatic lesions with a decrease in tumor cell proliferation independent of treatment response. The antiproliferative response was seen in both basal and classical PDA subtypes. PDA subtype was not associated with survival outcomes; instead, genes involved in immune activation distinguished responders from non-responders. Tumor response was associated with an increase in CD3+ and CD8+ T-cell infiltrates into metastatic lesions. A composite of decreased tumor proliferation in response to treatment and increased CD8 T-cell infiltration in metastatic lesions identified responders and associated with a favorable survival outcome.
Conclusions:
Our findings suggest that inhibiting cancer cell proliferation alone in PDA is insufficient to produce tumor responses and support a role for tumor-extrinsic mechanisms, such as CD8+ T cells, which combine with the cancer cell proliferation index to define treatment outcomes.