bluuebunny/crossref_metadata_2025 huggingface dataset:
Data from Hepatocellular Carcinoma Surveillance Among Individuals with Cirrhosis: Trends by Payer, Etiology and Calendar Year, from a Statewide, Multi-Payer Dataset, 2010-2018
Authors: Hsu Christine D. , Henderson Louise M. , Jackson Bradford E. , Baggett Christopher D. , Jonsson Funk Michele , Olshan Andrew F. , Gupta Parul , Barritt A Sidney. , Sanoff Hanna K. , Wheeler Stephanie B. , Moon Andrew M. , Lund Jennifer L.
Published: September 2024

Abstract
Background. Hepatocellular carcinoma surveillance is underutilized, with <25% of individuals with cirrhosis receiving surveillance exams as recommended. The epidemiology of cirrhosis and HCC in the US has also shifted in recent years, but little is known about recent trends in surveillance utilization. We characterized patterns of HCC surveillance by payer, cirrhosis etiology, and calendar year in insured individuals with cirrhosis.

Methods. We conducted a retrospective cohort study of individuals with cirrhosis using claims data from Medicare, Medicaid, and private insurance plans in North Carolina. We included individuals ≥18 years with a first occurrence of an ICD-9/10 code for cirrhosis between January 1, 2010, and June 30, 2018. The outcome was HCC surveillance by abdominal ultrasound, computed tomography, or magnetic resonance imaging. We estimated 1- and 2-year cumulative incidences for HCC surveillance and assessed longitudinal adherence to surveillance by computing the proportion of time covered (PTC).

Results. Among 46,052 individuals, 71% were enrolled through Medicare, 15% through Medicaid, and 14% through private insurance. The overall 1-year cumulative incidence of HCC surveillance was 49% and the 2-year cumulative incidence was 55%. For those with an initial screen in the first six months of their cirrhosis diagnosis, the median 2-year PTC was 67% (Q1, 38%; Q3, 100%).
Conclusion. HCC surveillance initiation after cirrhosis diagnosis remains low, though it has improved slightly over time, particularly among individuals with Medicaid.

Impact. This study provides insight into recent trends in HCC surveillance and highlights areas to target for future interventions, particularly among patients with non-viral etiologies.
Data from Medical Financial Hardship and Food Security among Cancer Survivors in the
United States
Authors: Hallgren Emily , Narcisse Marie-Rachelle , Andersen Jennifer A. , Willis Don E. , Thompson Tess , Bryant-Smith Gwendolyn , McElfish Pearl A.
Published: September 2024

Abstract
Background: Some cancer survivors experience medical financial hardship, which may reduce their food security. The purpose of this study was to explore whether medical financial hardship is related to food security among cancer survivors.
Methods: The study was based on cross-sectional data from the 2020 National Health Interview Survey. We used ordinal logistic regression to examine the relationship between material, psychological, and behavioral medical financial hardship and household food security (i.e., high, marginal, low, or very low) among individuals aged ≥ 18 years who reported a cancer diagnosis from a health professional (N=4,130).
Results: The majority of the sample reported high household food security (88.5%), with 4.8% reporting marginal, 3.6% reporting low, and 3.1% reporting very low household food security. In the adjusted model, the odds of being in a lower food security category were higher for cancer survivors who had problems paying or were unable to pay their medical bills compared to those who did not (OR=1.73, 95% CI, 1.06-2.82, p=0.027), who were very worried about paying their medical bills compared to those who were not at all worried (OR=2.88, 95% CI, 1.64-5.07, p<0.001), and who delayed medical care due to cost compared to those who did not (OR=2.56, 95% CI, 1.29-5.09, p=0.007).
Conclusions: Food insecurity is rare among cancer survivors. However, medical financial hardship is associated with an increased risk of lower household food security among cancer survivors.
Impact: A minority of cancer survivors experience medical financial hardship and food insecurity; social needs screenings should be conducted.
Data from Sleep Behaviors, Genetic Predispositions, and Risk of Esophageal Cancer
Authors: Wang Xiaoyan , Tian Ruiyi , Zong Xiaoyu , Jeon Myung Sik , Luo Jingqin , Colditz Graham A. , Wang Jean S. , Tsilidis Konstantinos K. , Ju Yo-El S. , Govindan Ramaswamy , Puri Varun , Cao Yin
Published: September 2024

Abstract
Background: Risk factors contributing to more than tenfold increase in esophageal cancer in the last 50 years remain underexplored. We aim to examine the associations of sleep behaviors with esophageal adenocarcinoma (EAC) and squamous cell carcinoma (ESCC).

Methods: We prospectively assessed the associations between sleep behaviors (chronotype, duration, daytime napping, daytime sleepiness, snoring, and insomnia) and EAC and ESCC risk in 393,114 participants in the UK Biobank (2006-2016). Participants with 0, 1, and ≥2 unhealthy behaviors, including sleep <6 or >9 h/day, daytime napping, and usual daytime sleepiness were classified as having a good, intermediate, and poor sleep. For EAC, we also examined interactions with polygenic risk score (PRS). Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).

Results: We documented 294 incident EAC and 95 ESCC. Sleep >9 h/day (HR=2.05, 95%CI: 1.18, 3.57) and sometimes daytime napping (HR=1.36, 95%CI: 1.06, 1.75) were individually associated with increased EAC risk. Compared with individuals with good sleep, those with intermediate sleep had a 47% (HR=1.47, 95%CI: 1.13, 1.91) increased EAC risk, and those with poor sleep showed a 87% (HR=1.87, 95%CI: 1.24, 2.82) higher risk (Ptrend<0.001). The elevated risks for EAC were similar within strata of PRS (Pinteraction=0.884). Evening chronotype was associated with elevated risk of ESCC diagnosed after 2 years of enrollment (HR=2.79, 95%CI: 1.32, 5.88).

Conclusions: Unhealthy sleep behaviors were associated with an increased risk of EAC, independent of genetic risk.

Impact: Sleep behaviors may serve as modifiable factors for the prevention of EAC.
Data from Field synopsis of environmental and genetic risk factors of sporadic early-onset colorectal cancer and advanced adenoma
Authors: Zhang Rongqi , Boakye Daniel , Yang Nan , Zhou Xuan , Zhou Yajing , Jiang Fangyuan , Yu Lili , Wang Lijuan , Sun Jing , Yuan Shuai , Chen Jie , Hamilton Ashleigh C. , Coleman Helen G. , Larsson Susanna C. , Little Julian , Dunlop Malcolm G. , Giovannucci Edward L. , Theodoratou Evropi , Li Xue
Published: September 2024

Abstract
Background:To systematically appraise and synthesize available epidemiological evidence on the associations of environmental and genetic factors with the risk of sporadic early-onset colorectal cancer (EOCRC) and early-onset advanced colorectal adenoma (EOCRA).

Methods:Multiple databases were comprehensively searched to identify eligible observational studies. Genotype data from UK Biobank were incorporated to examine their associations with EOCRC in a nested case-control design. Meta-analyses of environmental risk factors were performed and the strength of evidence was graded based on predefined criteria. Meta-analyses of genetic associations were conducted using the allelic, recessive, and dominant model, respectively.

Results:A total of 61 studies were included, reporting 120 environmental factors and 62 genetic variants. We found 12 risk factors (current overweight, overweight in adolescence, high waist circumference, smoking, alcohol, sugary beverages intake, sedentary behavior, red meat intake, family history of CRC, hypertension, hyperlipidemia and metabolic syndrome) and three protective factors (vitamin D, folate, and calcium intake) for EOCRC or EOCRA. No significant associations between the examined genetic variants and EOCRC risk were observed.

Conclusions: Recent data indicate that the changing patterns of traditional CRC risk factors may explain the rising incidence of EOCRC. However, research on novel risk factors for EOCRC is limited; therefore, we cannot rule out the possibility of EOCRC having different risk factors than LOCRC.

Impact: The potential for the identified risk factors to enhance the identification of at-risk groups for personalized EOCRC screening and prevention and for the prediction of EOCRC risk should be comprehensively addressed by future studies.
Data from Sex-specific associations between adiponectin and leptin signaling and pancreatic cancer survival
Authors: Babic Ana , Wang Qiao-Li , Lee Alice A. , Yuan Chen , Rifai Nader , Luo Juhua , Tabung Fred K. , Shadyab Aladdin , Wactawski-Wende Jean , Saquib Nazmus , Kim Jihye , Kraft Peter , Sesso Howard D. , Buring Julie E. , Giovannucci Edward L. , Manson JoAnn E. , Stampfer Meir J. , Ng Kimmie , Fuchs Charles S. , Wolpin Brian M.
Published: September 2024

Abstract
Background: Circulating adiponectin and leptin have been associated with risk of pancreatic cancer. However, the relationship between long-term exposure to these adipokines in the prediagnostic period with patient survival has not been investigated.

Methods: Adipokine levels were measured in prospectively collected samples from 472 pancreatic cancer patients. Due to sex-specific differences in adipokine levels, associations were evaluated separately for men and women. In a subset of 415 patients, we genotyped 23 nucleotide polymorphisms (SNPs) in adiponectin receptor genes (ADIPOR1, ADIPOR2) and 30 SNPs in the leptin receptor gene (LEPR).

Results: Adiponectin levels were inversely associated with survival in women (HR=1.47, 95% CI: 1.03-2.11, comparing top to bottom quartile) but not in men (HR=0.93, 95% CI: 0.54-1.59). The SNPs rs10753929 and rs1418445 in ADIPOR1 were associated with survival in the combined population (per minor allele HR=0.66, 95% CI: 0.51-0.84, and HR=1.33, 95% CI: 1.12-1.58, respectively). Among SNPs in LEPR, rs12025906, rs3790431, and rs17127601 were associated with survival in the combined population [HRs (95% CI) of 1.54 (1.25-1.90), 0.72 (0.59-0.88), and 0.70 (0.56-0.89), respectively], while rs11585329 was associated with survival in men only (HR=0.39, 95% CI: 0.23-0.66) (P-interaction=0.0002).

Conclusions: High levels of adiponectin in the prediagnostic period were associated with shorter survival among women, but not among men with pancreatic cancer. Several polymorphisms in ADIPOR1 and LEPR are associated with patient survival.

Impact: Our findings reveal the association between adipokine signaling and pancreatic cancer survival and demonstrate the importance of examining obesity-associated pathways in relation to pancreatic cancer in a sex-specific manner.
Supplementary Figure S2 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 , Sundby Hall Kirsten , 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 2024

Kaplan-Meier estimates of recurrence-free survival of patients with KIT exon 11 substitution mutation (A) and patients with KIT exon 9 mutation (B). The 5-year and 10-year survival rates are shown. Censored patients are indicated with a bar
Supplementary Figure 2 from Clinicopathologic, genomic, and immunophenotypic landscape of ATM mutations in non-small cell lung cancer
Authors: Ricciuti Biagio , Elkrief Arielle , Alessi Joao , Wang Xinan , Li Yvonne , Gupta Hersh , Muldoon Daniel M. , Bertram Arrien A. , Pecci Federica , Lamberti Giuseppe , Di Federico Alessandro , Barrichello Adriana , Vaz Victor R. , Gandhi Malini , Lee Elinton , Shapiro Geoffrey I. , Park Hyesun , Nishino Mizuki , Lindsay James , Felt Kristen D. , Sharma Bijaya , Cherniack Andrew D. , Rodig Scott , Gomez Daniel R. , Shaverdian Narek , Rakaee Mehrdad , Bandlamudi Chaitanya , Ladanyi Marc , Janne Pasi A. , Schoenfeld Adam J. , Sholl Lynette M. , Awad Mark M. , Cheng Michael L.
Published: September 2024

Supplementary Figure 2. Proportion of samples with PD-L1 TPS ≥1%, ≥50%, ≥90% according to ATM mutation status (ATMMUT versus ATMWT).
Supplementary Figure 17 from Clinicopathologic, genomic, and immunophenotypic landscape of ATM mutations in non-small cell lung cancer
Authors: Ricciuti Biagio , Elkrief Arielle , Alessi Joao , Wang Xinan , Li Yvonne , Gupta Hersh , Muldoon Daniel M. , Bertram Arrien A. , Pecci Federica , Lamberti Giuseppe , Di Federico Alessandro , Barrichello Adriana , Vaz Victor R. , Gandhi Malini , Lee Elinton , Shapiro Geoffrey I. , Park Hyesun , Nishino Mizuki , Lindsay James , Felt Kristen D. , Sharma Bijaya , Cherniack Andrew D. , Rodig Scott , Gomez Daniel R. , Shaverdian Narek , Rakaee Mehrdad , Bandlamudi Chaitanya , Ladanyi Marc , Janne Pasi A. , Schoenfeld Adam J. , Sholl Lynette M. , Awad Mark M. , Cheng Michael L.
Published: September 2024

Supplementary Figure 17. (A) Objective response rate, (B) progression-free survival, and (C) overall survival to PD-(L)1 inhibition among patients with advanced/metastatic NSCLC, according to ATM expression by immunohistochemistry.
Supplementary Figure 16 from Clinicopathologic, genomic, and immunophenotypic landscape of ATM mutations in non-small cell lung cancer
Authors: Ricciuti Biagio , Elkrief Arielle , Alessi Joao , Wang Xinan , Li Yvonne , Gupta Hersh , Muldoon Daniel M. , Bertram Arrien A. , Pecci Federica , Lamberti Giuseppe , Di Federico Alessandro , Barrichello Adriana , Vaz Victor R. , Gandhi Malini , Lee Elinton , Shapiro Geoffrey I. , Park Hyesun , Nishino Mizuki , Lindsay James , Felt Kristen D. , Sharma Bijaya , Cherniack Andrew D. , Rodig Scott , Gomez Daniel R. , Shaverdian Narek , Rakaee Mehrdad , Bandlamudi Chaitanya , Ladanyi Marc , Janne Pasi A. , Schoenfeld Adam J. , Sholl Lynette M. , Awad Mark M. , Cheng Michael L.
Published: September 2024

Supplementary Figure 16. (A) Objective response rate, (B) progression-free survival, and (C) overall survival to PD-(L)1 inhibition monotherapy among patients with advanced/metastatic NSCLC, according to ATM/TP53 co-mutation status. (D) Objective response rate, (E) progression-free survival, and (F) overall survival to PD-(L)1 inhibition in combination with chemotherapy among patients with advanced NSCLC, according to ATM/TP53 co-mutation status.
Supplementary Figure 13 from Clinicopathologic, genomic, and immunophenotypic landscape of ATM mutations in non-small cell lung cancer
Authors: Ricciuti Biagio , Elkrief Arielle , Alessi Joao , Wang Xinan , Li Yvonne , Gupta Hersh , Muldoon Daniel M. , Bertram Arrien A. , Pecci Federica , Lamberti Giuseppe , Di Federico Alessandro , Barrichello Adriana , Vaz Victor R. , Gandhi Malini , Lee Elinton , Shapiro Geoffrey I. , Park Hyesun , Nishino Mizuki , Lindsay James , Felt Kristen D. , Sharma Bijaya , Cherniack Andrew D. , Rodig Scott , Gomez Daniel R. , Shaverdian Narek , Rakaee Mehrdad , Bandlamudi Chaitanya , Ladanyi Marc , Janne Pasi A. , Schoenfeld Adam J. , Sholl Lynette M. , Awad Mark M. , Cheng Michael L.
Published: September 2024

Supplementary Figure 13. Overall survival since the date of initial diagnosis among patients with stage IV NSCLC according to ATM expression by immunohistochemistry.
Supplementary Figure S3 from Type 2 diabetes mellitus and efficacy outcomes from imune 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: September 2024

Kaplan-Meier survival estimates according to the receipt of metformin. A) Overall Survival whole cohort; patients on metformin: 12.4 months (95%CI: 10.5-16.3; 100 events), patients not receiving metformin: 19.0 months (95%CI: 16.4 – 21.1; 732 events). B) Progression Free Survival whole cohort; patients on metformin: 7.9 months (95%CI: 5.3-10.1; 124 events), patients not receiving metformin: 8.3 months (95%CI: 7.3 – 9.5; 933 events).
Supplementary Figure 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: September 2024

Figure S1. Diagram for study cohort derivation
Supplementary Tables 1-8 from Alternating 17beta-estradiol and aromatase inhibitor therapies is efficacious in post-menopausal women with advanced endocrine-resistant ER+ breast cancer
Authors: Schwartz Gary N. , Kaufman Peter A. , Giridhar Karthik V. , Marotti Jonathan D. , Chamberlin Mary D. , Arrick Bradley A. , Makari-Judson Grace , Goetz Matthew P. , Soucy Shannon M. , Kolling Fred , Demidenko Eugene , Miller Todd W.
Published: September 2024

Suppl. Tables S1-S8
Figure S1 from The Immunogenomic Landscape of Neuroendocrine Prostate Cancer
Authors: Bhinder Bhavneet , Ferguson Alison , Sigouros Michael , Uppal Manik , Elsaeed Ahmed G. , Bareja Rohan , Alnajar Hussein , Eng Kenneth Wha. , Conteduca Vincenza , Sboner Andrea , Mosquera Juan Miguel , Elemento Olivier , Beltran Himisha
Published: September 2024

Suppl Figure 1. Classification of prostate tumors based on T-cell immune status
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 2024

Supplementary table
Supplementary Data 1 from Genetic alterations detected by circulating tumor DNA in HER2-low metastatic breast cancer
Authors: Hensing Whitney L. , Gerratana Lorenzo , Clifton Katherine , Medford Arielle J. , Velimirovic Marko , Shah Ami N. , D'Amico Paolo , Reduzzi Carolina , Zhang Qiang , Dai Charles S. , Denault Elyssa N. , Bagegni Nusayba A. , Opyrchal Mateusz , Ademuyiwa Foluso O. , Bose Ron , Behdad Amir , Ma Cynthia X. , Bardia Aditya , Cristofanilli Massimo , Davis Andrew A.
Published: September 2024

HER2 subtype and genomic alterations for all patients
Supplemental Figure 3 from Early changes in circulating cell free KRAS G12C predicts response to adagrasib in KRAS mutant non-small cell lung cancer patients
Authors: Paweletz Cloud P. , Heavey Grace A. , Kuang Yanan , Durlacher Emily , Kheoh Thian , Chao Richard C. , Spira Alexander I. , Leventakos Konstantinos , Johnson Melissa L. , Ou Sai-Hong Ignatius. , Riely Gregory J. , Anderes Kenna , Yang Wenjing , Christensen James G. , Janne Pasi A.
Published: September 2024

Supplemental Figure 3: Baseline AF% of patients with complete clearance and patients with
incomplete clearance at C2.
Supplementary Figure S1 from Autocrine 17-β-estradiol/estrogen receptor-α loop determines the response to immune-checkpoint inhibitors in non-small cell lung cancer
Authors: Anobile Dario P. , Salaroglio Iris C. , Tabbò Fabrizio , La Vecchia Sofia , Akman Muhlis , Napoli Francesca , Bungaro Maristella , Benso Federica , Aldieri Elisabetta , Bironzo Paolo , Kopecka Joanna , Passiglia Francesco , Righi Luisella , Novello Silvia , Scagliotti Giorgio V. , Riganti Chiara
Published: September 2024

Outcome of non-small cell lung cancer patients, disaggregated according to gender, PD-L1 and ERα levels. Best response (PD: progressive disease; PR: partial response; SD: stable disease) after 6 months from the beginning of pembrolizumab treatment as first-line monotherapy, PFS and OS (Kapan-Meier and log-rank test) were analyzed in 35 NSCLC patients (15 females; 20 males). a-c. Female (F) and male (M) patients were stratified in CD274/PD-L1low and CD274/PD-L1high, according to the median value of the CD274/PD-L1mRNA, measured by RT-PCR in the tumor samples (technical triplicates). d-f. F and M patients were stratified in ESR1/ERαlow and ESR1/ERαhigh, according to the median value of the ESR1/ERα mRNA, measured by RT-PCR in the tumor samples (technical triplicates).
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 2024

Supplementary Table S3. Cluster marker genes of the Fibroblast populations.
Supplementary Fig. 6 from Discovery and targeting of a noncanonical mechanism of sarcoma resistance to ADI-PEG20 mediated by the microenvironment
Authors: Rogers Leonard C. , Kremer Jeff C. , Brashears Caitlyn B. , Lin Zongtao , Hu Zhixian , Bastos Alliny C. S. , Baker Adriana , Fettig Nicole , Zhou Dong , Shoghi Kooresh I. , Dehner Carina A. , Chrisinger John S. A. , Bomalaski John S. , Garcia Benjamin A. , Oyama Toshinao , White Eileen P. , Van Tine Brian A.
Published: September 2024

Supplemental Figure 6. RNA sequencing of tumors.
Supplementary Figure S2 from Associations between AI-assisted tumor amphiregulin and epiregulin IHC and outcomes from anti-EGFR therapy in the routine management of metastatic colorectal cancer
Authors: Williams Christopher J.M. , Elliott Faye , Sapanara Nancy , Aghaei Faranak , Zhang Liping , Muranyi Andrea , Yan Dongyao , Bai Isaac , Zhao Zuo , Shires Michael , Wood Henry M. , Richman Susan D. , Hemmings Gemma , Hale Michael , Bottomley Daniel , Galvin Leanne , Cartlidge Caroline , Dance Sarah , Bacon Chris M. , Mansfield Laura , Young-Zvandasara Kathe , Sudan Ajay , Lambert Katy , Bibby Irena , Coupland Sarah E. , Montazeri Amir , Kipling Natalie , Hughes Kathryn , Cross Simon S. , Dewdney Alice , Pheasey Leanne , Leng Cathryn , Gochera Tatenda , Mangham D Chas , Saunders Mark , Pritchard Martin , Stott Helen , Mukherjee Abhik , Ilyas Mohammad , Silverman Rafael , Hyland Georgina , Sculthorpe Declan , Thornton Kirsty , Gould Imogen , O'Callaghan Ann , Brown Nicholas , Turnbull Samantha , Shaw Lisa , Seymour Matthew T. , West Nicholas P. , Seligmann Jenny F. , Singh Shalini , Shanmugam Kandavel , Quirke Philip
Published: September 2024

Study flow diagram
Supplementary Figure S4 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 2024

Assessment of correlation between EGFRm VAF in baseline plasma and investigator-assessed PFS in A, patients from the AURA3 trial, by treatment arm and B, patients from the FLAURA trial, by treatment arm. Abbreviations: CR, complete response; EGFRm, epidermal growth factor receptor mutation (ex19del or L858R); NE, not evaluable; PD, progressive disease; PFS, progression-free survival; PR, partial response; SD, stable disease; VAF, variant allelic fraction.
Supplementary Table S4 from Dissecting the mechanisms underlying the Cytokine Release Syndrome (CRS) mediated by T Cell Bispecific Antibodies
Authors: Leclercq-Cohen Gabrielle , Steinhoff Nathalie , Albertí-Servera Llucia , Nassiri Sina , Danilin Sabrina , Piccione Emily , Yángüez Emilio , Hüsser Tamara , Herter Sylvia , Schmeing Stephan , Gerber Petra , Schwalie Petra , Sam Johannes , Briner Stefanie , Jenni Sylvia , Bianchi Roberta , Biehl Marlene , Cremasco Floriana , Apostolopoulou Katerina , Haegel Hélène , Klein Christian , Umana Pablo , Bacac Marina
Published: September 2024

Supplementary Table S4. Specification of reagents for flow cytometry (In vivo work)
Supplementary Table S3 from Dissecting the mechanisms underlying the Cytokine Release Syndrome (CRS) mediated by T Cell Bispecific Antibodies
Authors: Leclercq-Cohen Gabrielle , Steinhoff Nathalie , Albertí-Servera Llucia , Nassiri Sina , Danilin Sabrina , Piccione Emily , Yángüez Emilio , Hüsser Tamara , Herter Sylvia , Schmeing Stephan , Gerber Petra , Schwalie Petra , Sam Johannes , Briner Stefanie , Jenni Sylvia , Bianchi Roberta , Biehl Marlene , Cremasco Floriana , Apostolopoulou Katerina , Haegel Hélène , Klein Christian , Umana Pablo , Bacac Marina
Published: September 2024

Supplementary Table S3. Specification of reagents for flow cytometry (HUVEC staining)
Supplementary Figure S2 from Dissecting the mechanisms underlying the Cytokine Release Syndrome (CRS) mediated by T Cell Bispecific Antibodies
Authors: Leclercq-Cohen Gabrielle , Steinhoff Nathalie , Albertí-Servera Llucia , Nassiri Sina , Danilin Sabrina , Piccione Emily , Yángüez Emilio , Hüsser Tamara , Herter Sylvia , Schmeing Stephan , Gerber Petra , Schwalie Petra , Sam Johannes , Briner Stefanie , Jenni Sylvia , Bianchi Roberta , Biehl Marlene , Cremasco Floriana , Apostolopoulou Katerina , Haegel Hélène , Klein Christian , Umana Pablo , Bacac Marina
Published: September 2024

Supplementary Figure S2. Proportions of T cells, monocytes and neutrophils in human whole blood after treatment with 0.2 μg/mL CD20-TCB
Table S4 from Results of an Open-label, Phase 1a/b Study of Pembrolizumab plus Olaratumab in Patients with Unresectable, Locally Advanced or Metastatic Soft Tissue Sarcoma
Authors: Schöffski Patrick , Bahleda Rastislav , Wagner Andrew J. , Burgess Melissa A. , Junker Niels , Chisamore Michael , Peterson Patrick , Szpurka Anna M. , Ceccarelli Matteo , Tap William D.
Published: September 2024

Table S4: Representativeness of Study Participants.
Figure S2 from Results of an Open-label, Phase 1a/b Study of Pembrolizumab plus Olaratumab in Patients with Unresectable, Locally Advanced or Metastatic Soft Tissue Sarcoma
Authors: Schöffski Patrick , Bahleda Rastislav , Wagner Andrew J. , Burgess Melissa A. , Junker Niels , Chisamore Michael , Peterson Patrick , Szpurka Anna M. , Ceccarelli Matteo , Tap William D.
Published: September 2024

Figure S2: Waterfall plot for percent change in tumor size in cohort 1, cohort 2, and the dose-expansion cohort.
Supplementary Figure S17 from Trackable Intratumor Microdosing and Spatial Profiling Provide Early Insights into Activity of Investigational Agents in the Intact Tumor Microenvironment
Authors: Derry Jonathan M.J. , Burns Connor , Frazier Jason P. , Beirne Emily , Grenley Marc , DuFort Christopher C. , Killingbeck Emily , Leon Michael , Williams Claire , Gregory Mark , Houlton Jeffrey , Clayburgh Daniel , Swiecicki Paul , Huszar Dennis , Berger Allison , Klinghoffer Richard A.
Published: September 2024

Subasumstat-induced Interferon signature expression level is predicted by the CD8/CD68 ratio of the baseline tumor
Supplementary Figure S1 from Multiomic mapping of acquired chromosome 1 copy number and structural variants to identify therapeutic vulnerabilities in multiple myeloma.
Authors: Boyle Eileen M. , Blaney Patrick , Stoeckle James H. , Wang Yubao , Ghamlouch Hussein , Gagler Dylan , Braunstein Marc , Williams Louis , Tenenbaum Avital , Siegel Ariel , Chen Xiaoyi , Varma Gaurav , Avigan Jason , Li Alexander , Jinsi Monica , Kaminetzky David , Arbini Arnaldo , Montes Lydia , Corre Jill , Rustad Even H. , Landgren Ola , Maura Francesco , Walker Brian A. , Bauer Michael , Bruno Benedetto , Tsirigos Aristotelis , Davies Faith E. , Morgan Gareth J.
Published: September 2024

Recurrent chromosome 1 mutations. Ninety-five genes on chromosome 1 that are mutated in more than 1% of cases in the Myeloma Genome Project dataset.
Supplemental Figures 1 from Specific targeting of Multiple Myeloma by Dual Split-signaling Chimeric Antigen Receptors T-cells directed against CD38 and CD138
Authors: van der Schans Jort J. , Wang Ziyu , van Arkel Jennemiek , van Schaik Thijs , Katsarou Afroditi , Ruiter Ruud , Baardemans Thomas , Yuan Huipin , de Bruijn Joost , Zweegman Sonja , van de Donk Niels W.C.J. , Groen Richard W.J. , Themeli Maria , Mutis Tuna
Published: September 2024

Supplemental Figures
Supplementary Table S16 from Comprehensive analysis of tumor microenvironment reveals prognostic ceRNA network related to immune infiltration in sarcoma
Authors: Leng Dongliang , Yang Ziyi , Sun Heng , Song Chengcheng , Huang Chen , Ip Ka U. , Chen Guokai , Deng Chu-Xia , Zhang Xiaohua Douglas. , Zhao Qi
Published: September 2024

Supplementary Table S16. Cell types determination based on different annotation references.
Supplementary Data 1 from A Phase II Trial of the CD40 Agonist Sotigalimab (APX005M) in Combination with Nivolumab in Subjects with Metastatic Melanoma with Disease Progression on Anti-PD-1
Authors: Weiss Sarah A. , Sznol Mario , Shaheen Montaser , Berciano-Guerrero Miguel-Angel , Muñoz-Couselo Eva , Rodríguez-Abreu Delvys , Boni Valentina , Schuchter Lynn M. , Gonzalez Cao Maria , Arance Fernandez Ana , Wei Wei , Ganti Apar Kishor , Hauke Ralph J. , Berrocal Alfonso , Iannotti Nicholas O. , Hsu Frank J. , Kluger Harriet M.
Published: September 2024

Representativeness of Study Participants
Supplementary Information 1 from Urinary tumor DNA MRD analysis to identify responders to neoadjuvant immunotherapy in muscle-invasive bladder cancer
Authors: Zhang Ruiyun , Zang Jingyu , Jin Di , Xie Feng , Shahatiaili Akezhouli , Wu Guangyu , Zhang Lu , Wang Lu , Zhang Yue , Zhao Zhixin , Du Pan , Jia Shidong , Fan Jinhai , Zhuang Guanglei , Chen Haige
Published: September 2024

Supplementary methods and clinical trial protocol
Supplementary Data TS1 from Therapeutic Vaccination against Human Papillomavirus Type 16 for the Treatment of Anal Intraepithelial Neoplasia in HIV+ Men
Authors: Gosens Karien C.M. , van der Burg Sjoerd H. , Welters Marij J.P. , Boekestijn Sanne , Loof Nikki M. , Quint Wim G.V. , van Noesel Carel J.M. , van der Wal Allard C. , Richel Olivier , Krebber Wilhelmus J.T.A. , Melief Cornelis J.M. , de Vries Henry J.C. , Prins Jan M.
Published: September 2024

Supplementary Table S1: Proliferative T-cell responses determined by Lymphocyte Stimulation Test (LST).
Supplementary Data FS2 from Therapeutic Vaccination against Human Papillomavirus Type 16 for the Treatment of Anal Intraepithelial Neoplasia in HIV+ Men
Authors: Gosens Karien C.M. , van der Burg Sjoerd H. , Welters Marij J.P. , Boekestijn Sanne , Loof Nikki M. , Quint Wim G.V. , van Noesel Carel J.M. , van der Wal Allard C. , Richel Olivier , Krebber Wilhelmus J.T.A. , Melief Cornelis J.M. , de Vries Henry J.C. , Prins Jan M.
Published: September 2024

Supplementary Figure S2: HPV16-specific T cell responses at different dose levels and time points.
Supplementary Table S6 from Single-cell RNA analysis reveals cell-intrinsic functions of CAR-T cells correlating with response in a phase II study of lymphoma patients
Authors: Sarén Tina , Ramachandran Mohanraj , Gammelgård Gustav , Lövgren Tanja , Mirabello Claudio , Björklund Åsa K. , Wikström Kristina , Hashemi Jamileh , Freyhult Eva , Ahlström Håkan , Amini Rose-Marie , Hagberg Hans , Loskog Angelica , Enblad Gunilla , Essand Magnus
Published: September 2024

Gene list used for computing AUCell signatures
Supplementary Figure S3 from Single-cell RNA analysis reveals cell-intrinsic functions of CAR-T cells correlating with response in a phase II study of lymphoma patients
Authors: Sarén Tina , Ramachandran Mohanraj , Gammelgård Gustav , Lövgren Tanja , Mirabello Claudio , Björklund Åsa K. , Wikström Kristina , Hashemi Jamileh , Freyhult Eva , Ahlström Håkan , Amini Rose-Marie , Hagberg Hans , Loskog Angelica , Enblad Gunilla , Essand Magnus
Published: September 2024

Supplementary Figure S3. Responding patients had a better OS and PFS compared to nonresponding patients.
Figure S3 from HDACi-dependent microenvironmental normalization overcomes tumor burden-induced T-cell exhaustion
Authors: Nguyen Andrew , Brown Dominique , Krishnan Ramya , Bastin Donald , Deng Li , Chen Lan , Salem Omar , Walsh Scott R. , Bramson Jonathan L. , Wan Yonghong
Published: September 2024

Figure S3: CEMiTool module analysis and hub gene identification
Supplementary Table S1 from Safety, immunologic and clinical activity of Durvalumab in combination with Olaparib or Cediranib in advanced leiomyosarcoma: Results of the DAPPER clinical trial
Authors: Salawu Abdulazeez , Wang Ben X. , Han Ming , Geady Caryn , Heirali Alya , Berman Hal K. , Pfister Thomas D. , Hernando-Calvo Alberto , Al-Ezzi Esmail Mutahar. , Stayner Lee-Anne , Gupta Abha A. , Ayodele Olubukola , Lam Bernard , Hansen Aaron R. , Spreafico Anna , Bedard Philippe L. , Butler Marcus O. , Avery Lisa , Coburn Bryan , Haibe-Kains Benjamin , Siu Lillian L. , Abdul Razak Albiruni R.
Published: September 2024

Table S1: Best overall response (RECIST v1.1) of leiomyosarcoma patients on the DAPPER
study
Supplementary Methods S1 from Safety, immunologic and clinical activity of Durvalumab in combination with Olaparib or Cediranib in advanced leiomyosarcoma: Results of the DAPPER clinical trial
Authors: Salawu Abdulazeez , Wang Ben X. , Han Ming , Geady Caryn , Heirali Alya , Berman Hal K. , Pfister Thomas D. , Hernando-Calvo Alberto , Al-Ezzi Esmail Mutahar. , Stayner Lee-Anne , Gupta Abha A. , Ayodele Olubukola , Lam Bernard , Hansen Aaron R. , Spreafico Anna , Bedard Philippe L. , Butler Marcus O. , Avery Lisa , Coburn Bryan , Haibe-Kains Benjamin , Siu Lillian L. , Abdul Razak Albiruni R.
Published: September 2024

Supplementary Methods
Supplementary Table S8 from SPOP mutations target STING1 signaling in prostate cancer and create therapeutic vulnerabilities to PARP inhibitor–induced growth suppression
Authors: Geng Chuandong , Zhang Man-Chao , Manyam Ganiraju C. , Vykoukal Jody V. , Fahrmann Johannes F. , Peng Shan , Wu Cheng , Park Sanghee , Kondraganti Shakuntala , Wang Daoqi , Robinson Brian D. , Loda Massimo , Barbieri Christopher E. , Yap Timothy A. , Corn Paul G. , Hanash Samir , Broom Bradley M. , Pilie Patrick G. , Thompson Timothy C.
Published: September 2024

Supplementary Table S8. Quantification of each protein-specific band normalized to vinculin (Dox-inducible RM-1-BM– and C4-2b–derived models, Fig. 3A, 3B).
Supplementary Table S4 from SPOP mutations target STING1 signaling in prostate cancer and create therapeutic vulnerabilities to PARP inhibitor–induced growth suppression
Authors: Geng Chuandong , Zhang Man-Chao , Manyam Ganiraju C. , Vykoukal Jody V. , Fahrmann Johannes F. , Peng Shan , Wu Cheng , Park Sanghee , Kondraganti Shakuntala , Wang Daoqi , Robinson Brian D. , Loda Massimo , Barbieri Christopher E. , Yap Timothy A. , Corn Paul G. , Hanash Samir , Broom Bradley M. , Pilie Patrick G. , Thompson Timothy C.
Published: September 2024

Supplementary Table S4. Complete listing and details of oligonucleotide primers used for RT-qPCR analysis.
Supplementary Figure S2 from SPOP mutations target STING1 signaling in prostate cancer and create therapeutic vulnerabilities to PARP inhibitor–induced growth suppression
Authors: Geng Chuandong , Zhang Man-Chao , Manyam Ganiraju C. , Vykoukal Jody V. , Fahrmann Johannes F. , Peng Shan , Wu Cheng , Park Sanghee , Kondraganti Shakuntala , Wang Daoqi , Robinson Brian D. , Loda Massimo , Barbieri Christopher E. , Yap Timothy A. , Corn Paul G. , Hanash Samir , Broom Bradley M. , Pilie Patrick G. , Thompson Timothy C.
Published: September 2024

Supplementary Fig. S2. Original unedited IB images for representative Western blots experiments used in Figure 2B and 2C
Data from A Phase II Trial of Guadecitabine plus Atezolizumab in Metastatic Urothelial Carcinoma Progressing after Initial Immune Checkpoint Inhibitor Therapy
Authors: Jang H. Josh , Hostetter Galen , MacFarlane Alexander W. , Madaj Zachary , Ross Eric A. , Hinoue Toshinori , Kulchycki Justin R. , Burgos Ryan S. , Tafseer Mahvish , Alpaugh R. Katherine , Schwebel Candice L. , Kokate Rutika , Geynisman Daniel M. , Zibelman Matthew R. , Ghatalia Pooja , Nichols Peter W. , Chung Woonbok , Madzo Jozef , Hahn Noah M. , Quinn David I. , Issa Jean-Pierre J. , Topper Michael J. , Baylin Stephen B. , Shen Hui , Campbell Kerry S. , Jones Peter A. , Plimack Elizabeth R.
Published: September 2024

Abstract
Purpose: Based on preclinical evidence of epigenetic contribution to sensitivity and resistance to immune checkpoint inhibitors (ICI), we hypothesized that guadecitabine (hypomethylating agent) and atezolizumab (anti-PD-L1) together would potentiate a clinical response in patients with metastatic urothelial carcinoma (UC) unresponsive to initial immune checkpoint blockade therapy. Patients and Methods:We designed a single arm Phase II study (NCT03179943) with a safety run-in to identify the recommended phase II dose of the combination therapy of guadecitabine and atezolizumab. Patients with recurrent/advanced urothelial carcinoma who had previously progressed on ICI therapy with PD-1 or PD-L1 targeting agents were eligible. Pre-planned correlative analysis was performed to characterize peripheral immune dynamics and global DNA methylation, transcriptome, and immune infiltration dynamics of patient tumors. Results: Safety run-in enrolled 6 patients and Phase II enrolled 15 patients before the trial was closed for futility. No dose-limiting toxicity was observed. Four patients, with best response of stable disease, exhibited extended tumor control (8-11 months) and survival (>14 months). Correlative analysis revealed lack of DNA demethylation in tumors after 2 cycles of treatment. Increased peripheral immune activation and immune infiltration in tumors after treatment correlated with progression-free survival and stable disease. Furthermore, high IL-6 and IL-8 levels in the patients’ plasma associates with short survival. Conclusions: No RECIST responses were observed after combination therapy in this trial. Although we could not detect the anticipated tumor-intrinsic effects of guadecitabine, the addition of hypomethylating agent to ICI therapy induced immune activation in a few patients, which associated with longer patient survival.
Data from Preclinical Efficacy of the Antibody-Drug-Conjugate CLDN6-23-ADC for the Treatment of CLDN6 Positive Solid Tumors
Authors: McDermott Martina S.J. , O'Brien Neil A. , Hoffstrom Benjamin , Gong KeWei , Lu Ming , Zhang Jun , Luo Tong , Liang Min , Jia Weiping , Hong Jenny , Chau Kevin , Davenport Simon , Xie Bin , Press Michael F. , Panayiotou Richard , Handly-Santana Abram , Brugge Joan S. , Presta Leonard , Glaspy John , Slamon Dennis J.
Published: September 2024

Abstract
Purpose: Claudin-6 (CLDN6) is expressed at elevated levels in multiple human cancers including ovarian and endometrial malignancies, with little or no detectable expression in normal adult tissue. This expression profile makes CLDN6 an ideal target for development of a potential therapeutic antibody-drug-conjugate (ADC). This study describes the generation and preclinical characterization of CLDN6-23-ADC, an ADC consisting of a humanized anti-CLDN6 monoclonal antibody coupled to MMAE via a cleavable linker. Experimental Design: A fully humanized anti-CLDN6 antibody was conjugated to MMAE resulting in the potential therapeutic ADC, CLDN6-23-ADC. The anti-tumor efficacy of CLDN6-23-ADC was assessed for anti-tumor efficacy in CLDN6-positive (CLDN6+) and negative (CLDN6-) xenografts and patient-derived xenograft (PDX) models of human cancers. Results: CLDN6-23-ADC selectively binds to CLDN6, versus other CLDN family members, inhibits the proliferation of CLDN6+ cancer cells in vitro and is rapidly internalized in CLDN6+ cells. Robust tumor regressions were observed in multiple CLDN6+ xenograft models and tumor inhibition lead to markedly enhanced survival of CLDN6+ PDX tumors following treatment with CLDN6-23-ADC. IHC assessment of ovarian cancer tissue microarrays demonstrate elevated levels of CLDN6 in 29% of ovarian epithelial carcinomas. Approximately 45% of high-grade serous ovarian carcinomas and 11% of endometrial carcinomas are positive for the target. Conclusions: We report the development of a novel antibody-drug conjugate, CLDN6-23-ADC, that selectively targets CLDN6, a potential onco-fetal-antigen which is highly expressed in ovarian and endometrial cancers. CLDN6-23-ADC exhibits robust tumor regressions in mouse models of human ovarian and endometrial cancers and is currently undergoing Phase I study.
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 , Sundby Hall Kirsten , 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 2024

Abstract
Backgroud: Limited data are available about 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; hazard ratio [HR] 0.34, 95% CI: 0.15-0.72, P = 0.007), and had also 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 to 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 A tumor suppressive-molecular axis EP300/circRERE/miR-6837-3p/MAVS activates type I interferon pathway and anti-tumor immunity to suppress colorectal cancer
Authors: Ding Nan , You A-Bin , Yang Hu , Hu Guo-sheng , Lai Chun-Ping , Liu Wen , Ye Feng
Published: September 2024

Abstract
Purpose: The oncogenic role of circRNAs has been well-studied in cancers including colorectal cancer (CRC). However, tumor-suppressive circRNAs and the mechanism through which they exert their anti-tumor effects remain largely unknown. We aim to find out the critical tumor-suppressive circRNAs and their possibility to serve as gene therapy targets. Experimental Design: CircRNA sequencing, gain- and loss- of function experiments，and transcriptomic analysis were performed to find tumor-suppressive and anti-tumor immunity effects of circRERE. Molecular biology experiments were conducted for mechanism exploration. Finally, we conducted adeno-associated virus to deliver circRERE (circRERE-AAV) and evaluated circRERE-AAV alone and in combination with anti-PD-1 antibody in C57BL/6J mice bearing subcutaneous MC38 tumors. Results: CircRERE is lowly expressed in CRC. Overexpression of circRERE inhibits the malignant behaviors of CRC in vitro and in vivo, while knockdown exhibits the opposite effects. The expression of circRERE is regulated by EP300, a histone acetyltransferase downregulated in CRC as well. Mechanistically, circRERE acts as a ceRNA to sponge miR-6837-3p to upregulate MAVS expression, thereby activating type I IFN signaling and promoting anti-tumor immunity. Delivery of circRERE-AAV elicits significant anti-tumor effects, and combination treatment with circRERE-AAV and anti-PD-1 antibody exhibits synergistic effects on tumor growth in preclinical models of CRC. Conclusions: These results uncover modulatory axis constituting of EP300/circRERE/miR-6837-3p/MAVS and its essential roles in anti-tumor immunity, and demonstrate that circRERE-AAV might represent a new therapeutic avenue to prime immune responses and boost the effects of immunotherapy in clinic.
Data from Randomized Trial of Tepotinib Plus Gefitinib Versus Chemotherapy in EGFR-Mutant NSCLC with EGFR Inhibitor Resistance Due to MET Amplification: INSIGHT Final Analysis
Authors: Liam Chong Kin , Ahmad Azura Rozila , Hsia Te-Chun , Zhou Jianying , Kim Dong-Wan , Soo Ross Andrew. , Cheng Ying , Lu Shun , Shin Sang Won , Yang James Chi-Hsin , Zhang Yiping , Zhao Jun , Berghoff Karin , Bruns Rolf , Johne Andreas , Wu Yi-Long
Published: September 2024

Abstract
Purpose: The final analyses of the INSIGHT phase II study evaluating tepotinib (a selective MET inhibitor) plus gefitinib versus chemotherapy in patients with MET-altered EGFR-mutant NSCLC (data cut-off: September 3, 2021). Patients and methods: Adults with advanced/metastatic EGFR-mutant NSCLC, acquired resistance to first-/second-generation EGFR inhibitors, and MET gene copy number (GCN) ≥5, MET:CEP7 ≥2, or MET IHC 2+/3+ were randomized to tepotinib 500 mg (450 mg active moiety) plus gefitinib 250 mg once daily, or chemotherapy. Primary endpoint was investigator-assessed progression-free survival (PFS). MET-amplified subgroup analysis was preplanned. Results: Overall (N=55), median PFS was 4.9 versus 4.4 months (stratified HR 0.67 [90% CI: 0.35, 1.28]) with tepotinib plus gefitinib versus chemotherapy. In 19 patients with MET amplification (median age 60.4 years; 68.4% never-smokers; median GCN 8.8; median MET/CEP7 2.8; 89.5% with MET IHC 3+), tepotinib plus gefitinib improved PFS (HR 0.13; 90% CI: 0.04, 0.43) and overall survival (OS; HR 0.10; 90% CI: 0.02, 0.36) versus chemotherapy. Objective response rate was 66.7% with tepotinib plus gefitinib versus 42.9% with chemotherapy; median duration of response was 19.9 versus 2.8 months. Median duration of tepotinib plus gefitinib was 11.3 months (range: 1.1–56.5), with treatment >1 year in six (50.0%) and >4 years in three patients (25.0%). Seven patients (58.3%) had treatment-related grade ≥3 adverse events with tepotinib plus gefitinib, and five (71.4%) with chemotherapy. Conclusions: Final analysis of INSIGHT suggests improved PFS and OS with tepotinib plus gefitinib versus chemotherapy in a subgroup of patients with MET-amplified EGFR-mutant NSCLC, after progression on EGFR inhibitors.