bluuebunny/crossref_metadata_2025 huggingface dataset:
Supplementary Data1 from Metabolic Tumor Volume Assessed by 18F FDG–PET CT Scan as a Predictive Biomarker for Immune Checkpoint Blockers in Advanced NSCLC and Its Biological Correlates
Authors: Dall’Olio Filippo G. , Zrafi Wael , Roelants Veronique , Ambrosini Valentina , Fourquet Aloyse , Mitea Cristina , Passiglia Francesco , Bauckneht Matteo , Bonardel Gerald , Conci Nicole , Benitez Jose Carlos , Arena Vincenzo , Namour Céline , Naigeon Marie , Monnet Isabelle , Beshiri Kristi , Hoton Delphine , Dursun Safiye , Danlos François Xavier , Argalia Giulia , Aldea Mihaela , Rovera Guido , Derosa Lisa , Iebba Valerio , Gietema Hester A. , Gounant Valerie , Lacroix Valérie , Remon Jordi , Gautheret Daniel , Chaput Nathalie , Job Bastien , Kannouche Patricia L. , Velasco-Nuño Monica , Zitvogel Laurence , Cella Eugenia , Chícharo de Freitas José Reinaldo , Vasseur Damien , Bettaieb Mohamed Aymen , Tagliamento Marco , Hendriks Lizza , Italiano Antoine , Planchard David , Marabelle Aurelien , Barlesi Fabrice , Novello Silvia , De Andreis Desiree , Aboubakar Nana Frank , Ardizzoni Andrea , Zalcman Gerard , Garcia Camilo , Besse Benjamin
Published: January 2025

supplementary materials
Supplementary Table S1 from A Phase II Open-Label, Randomized Clinical Trial of Atezolizumab with or without Human Recombinant IL-7 (CYT107) in Advanced Urothelial Cancer
Authors: Sweis Randy F. , Chatta Gurkamal S. , Jain Rohit K. , Moon Helen , Delacroix Scott Edward , Fang Alana , D’Amico Leonard , Kask Angela Shaulov , Cheever Martin A. , Fling Steven , Sharon Elad , Lacroix Andreanne , Kaiser Judith C. , Pachynski Russell K. , Yu Evan Y.
Published: January 2025

Representativeness of Study Participants
Supplementary Figure S1 from Clinical Pharmacology of Cytokine Release Syndrome with T-Cell–Engaging Bispecific Antibodies: Current Insights and Drug Development Strategies
Authors: Radtke Kendra K. , Bender Brendan C. , Li Zao , Turner David C. , Roy Sumedha , Belousov Anton , Li Chi-Chung
Published: January 2025

Selected Cytokine Concentration-Time Profiles for Approved T-Cell Engaging Bispecific Antibodies (T-BiSp)
Supplementary Figure S4 from A Phase II Open-Label, Randomized Clinical Trial of Atezolizumab with or without Human Recombinant IL-7 (CYT107) in Advanced Urothelial Cancer
Authors: Sweis Randy F. , Chatta Gurkamal S. , Jain Rohit K. , Moon Helen , Delacroix Scott Edward , Fang Alana , D’Amico Leonard , Kask Angela Shaulov , Cheever Martin A. , Fling Steven , Sharon Elad , Lacroix Andreanne , Kaiser Judith C. , Pachynski Russell K. , Yu Evan Y.
Published: January 2025

Pharmacodynamics showing fold-change from baseline of % of T lymphocyte memory subsets for (A,C) CD4+ T cells and (B,D) CD8+ T cells. Tscm lymphocyte subset the most highly significantly expanded T cell subset for both CD4+ and CD8+ T cells and seen only in (A,B) experimental arm and not (C,D) control arm subjects. (E,F) CX3CR1 expression in CD4+ Tscm lymphocytes trended lower in responding patients. T lymphocytes were evaluated and analyzed by 14-color flow cytometry on cryopreserved PBMCs. TE = Terminal Effector, EM = Effector Memory, CM = Central Memory. N = Naïve, SCM = T memory Stem Cells.
Supplementary Table S4 from A Tumor-Naïve ctDNA Assay Detects Minimal Residual Disease in Resected Stage II or III Colorectal Cancer and Predicts Recurrence: Subset Analysis from the GALAXY Study in CIRCULATE-Japan
Authors: Nakamura Yoshiaki , Kaneva Kristiyana , Lo Christine , Neems Daniel , Freaney Jonathan E. , Boulos Hala , Hyun Seung Won , Islam Farahnaz , Yamada-Hanff Jason , Driessen Terri M. , Sonnenschein Anne , DeSantis Dana F. , Kotani Daisuke , Watanabe Jun , Kotaka Masahito , Mishima Saori , Bando Hideaki , Yamazaki Kentaro , Taniguchi Hiroya , Takemasa Ichiro , Kato Takeshi , Sangli Chithra , Tell Robert , Blidner Richard , Yoshino Takayuki , Sasser Kate , Oki Eiji , Nimeiri Halla
Published: January 2025

Table S4. Pre-surgery MRD association to DFS
Supplementary Table S2 from A Tumor-Naïve ctDNA Assay Detects Minimal Residual Disease in Resected Stage II or III Colorectal Cancer and Predicts Recurrence: Subset Analysis from the GALAXY Study in CIRCULATE-Japan
Authors: Nakamura Yoshiaki , Kaneva Kristiyana , Lo Christine , Neems Daniel , Freaney Jonathan E. , Boulos Hala , Hyun Seung Won , Islam Farahnaz , Yamada-Hanff Jason , Driessen Terri M. , Sonnenschein Anne , DeSantis Dana F. , Kotani Daisuke , Watanabe Jun , Kotaka Masahito , Mishima Saori , Bando Hideaki , Yamazaki Kentaro , Taniguchi Hiroya , Takemasa Ichiro , Kato Takeshi , Sangli Chithra , Tell Robert , Blidner Richard , Yoshino Takayuki , Sasser Kate , Oki Eiji , Nimeiri Halla
Published: January 2025

Table S2. Definitions for landmark and longitudinal true positive, false positive, true negative, and false negative cases
Supplementary Figure S3 from A Tumor-Naïve ctDNA Assay Detects Minimal Residual Disease in Resected Stage II or III Colorectal Cancer and Predicts Recurrence: Subset Analysis from the GALAXY Study in CIRCULATE-Japan
Authors: Nakamura Yoshiaki , Kaneva Kristiyana , Lo Christine , Neems Daniel , Freaney Jonathan E. , Boulos Hala , Hyun Seung Won , Islam Farahnaz , Yamada-Hanff Jason , Driessen Terri M. , Sonnenschein Anne , DeSantis Dana F. , Kotani Daisuke , Watanabe Jun , Kotaka Masahito , Mishima Saori , Bando Hideaki , Yamazaki Kentaro , Taniguchi Hiroya , Takemasa Ichiro , Kato Takeshi , Sangli Chithra , Tell Robert , Blidner Richard , Yoshino Takayuki , Sasser Kate , Oki Eiji , Nimeiri Halla
Published: January 2025

Figure S3. Site of clinical recurrence in longitudinal study
Supplementary Table S4 from Phase Ib Clinical and Pharmacodynamic Study of the TIE2 Kinase Inhibitor Rebastinib with Paclitaxel or Eribulin in HER2-Negative Metastatic Breast Cancer
Authors: Anampa Jesus D. , Flynn Daniel L. , Leary Cynthia , Oh Sun , Xue Xiaonan , Oktay Maja H. , Condeelis John S. , Sparano Joseph A.
Published: January 2025

Supplementary Table S4 shows treatment Related Adverse Events (TRAE) in the entire study (safety analysis set) by CTCAE grade (n = 27).
Supplementary Table S2 from Phase Ib Clinical and Pharmacodynamic Study of the TIE2 Kinase Inhibitor Rebastinib with Paclitaxel or Eribulin in HER2-Negative Metastatic Breast Cancer
Authors: Anampa Jesus D. , Flynn Daniel L. , Leary Cynthia , Oh Sun , Xue Xiaonan , Oktay Maja H. , Condeelis John S. , Sparano Joseph A.
Published: January 2025

Supplementary Table S2 shows Dose limiting toxicity evaluation in dose escalation phase.
Supplementary Figures 1 - 8 from Utilizing Patient-Derived Xenografts to Model Precision Oncology for Biliary Tract Cancer
Authors: DiPeri Timothy P. , Evans Kurt W. , Scott Stephen , Zheng Xiaofeng , Varadarajan Kaushik , Kwong Lawrence N. , Kahle Michael , Tran Cao Hop S. , Tzeng Ching-Wei , Vu Thuy , Kim Sunhee , Su Fei , Raso Maria Gabriela , Rizvi Yasmeen , Zhao Ming , Wang Huamin , Lee Sunyoung S. , Yap Timothy A. , Rodon Jordi , Javle Milind , Meric-Bernstam Funda
Published: January 2025

Figure S1, Figure S2, FIgure S3, Figure S4, Figure S5, Figure S6, Figure S7, Figure S8
Supplementary Figure S6 from Phase Ib Clinical and Pharmacodynamic Study of the TIE2 Kinase Inhibitor Rebastinib with Paclitaxel or Eribulin in HER2-Negative Metastatic Breast Cancer
Authors: Anampa Jesus D. , Flynn Daniel L. , Leary Cynthia , Oh Sun , Xue Xiaonan , Oktay Maja H. , Condeelis John S. , Sparano Joseph A.
Published: January 2025

Supplementary Figure S6 shows the effect of chemotherapy or rebastinib on mesenchymal CTC. A, Trends in mesenchymal CTC with rebastinib and rebastinib plus chemotherapy; B, trends in mesenchymal CTC with chemotherapy and rebastinib plus chemotherapy. Each line represent data from one patient over time. Abbreviations: C, Cycle; D, Day.
Supplementary Figure S5 from Phase Ib Clinical and Pharmacodynamic Study of the TIE2 Kinase Inhibitor Rebastinib with Paclitaxel or Eribulin in HER2-Negative Metastatic Breast Cancer
Authors: Anampa Jesus D. , Flynn Daniel L. , Leary Cynthia , Oh Sun , Xue Xiaonan , Oktay Maja H. , Condeelis John S. , Sparano Joseph A.
Published: January 2025

Supplementary Figure S5 shows the effect of chemotherapy or rebastinib on epithelial CTC. A, Trends in epithelial CTC with rebastinib and rebastinib plus chemotherapy; B, trends in epithelial CTC with chemotherapy and rebastinib plus chemotherapy. Each line represent data from one patient over time. Abbreviations: C, Cycle; D, Day.
Figure S6 from Divergent Clinical and Immunologic Outcomes Based on STK11 Co-mutation Status in Resectable KRAS-Mutant Lung Cancers Following Neoadjuvant Immune Checkpoint Blockade
Authors: Rosner Samuel , Connor Sydney , Sanber Khaled , Zahurak Marianna , Zhang Tianbei , Gurumurthy Isha , Zeng Zhen , Presson Brad , Singh Dipika , Rayes Roni , Sivapalan Lavanya , Pereira Gavin , Ji Zhicheng , Thummalapalli Rohit , Reuss Joshua E. , Broderick Stephen R. , Jones David R. , Deutsch Julie S. , Cottrell Tricia R. , Chaft Jamie E. , Spicer Jonathan , Taube Janis , Anagnostou Valsamo , Brahmer Julie R. , Pardoll Drew M. , Ji Hongkai , Forde Patrick M. , Marrone Kristen A. , Smith Kellie N.
Published: January 2025

Figure S6
Supplementary Figure S4 from Phase Ib Clinical and Pharmacodynamic Study of the TIE2 Kinase Inhibitor Rebastinib with Paclitaxel or Eribulin in HER2-Negative Metastatic Breast Cancer
Authors: Anampa Jesus D. , Flynn Daniel L. , Leary Cynthia , Oh Sun , Xue Xiaonan , Oktay Maja H. , Condeelis John S. , Sparano Joseph A.
Published: January 2025

Supplementary Figure S4 shows change in ocular pressure over time with rebastinib plus antitubulin therapy. (p value is derived from the Wilcoxon signed rank test comparing changes in ocular pressure over time within a rebastinib dose level. Paired samples for 50 mg dose = 6, paired samples for 100 mg dose = 10). Abbreviations: C5, Cycle five; C9, Cycle nine.
Figure S5 from Divergent Clinical and Immunologic Outcomes Based on STK11 Co-mutation Status in Resectable KRAS-Mutant Lung Cancers Following Neoadjuvant Immune Checkpoint Blockade
Authors: Rosner Samuel , Connor Sydney , Sanber Khaled , Zahurak Marianna , Zhang Tianbei , Gurumurthy Isha , Zeng Zhen , Presson Brad , Singh Dipika , Rayes Roni , Sivapalan Lavanya , Pereira Gavin , Ji Zhicheng , Thummalapalli Rohit , Reuss Joshua E. , Broderick Stephen R. , Jones David R. , Deutsch Julie S. , Cottrell Tricia R. , Chaft Jamie E. , Spicer Jonathan , Taube Janis , Anagnostou Valsamo , Brahmer Julie R. , Pardoll Drew M. , Ji Hongkai , Forde Patrick M. , Marrone Kristen A. , Smith Kellie N.
Published: January 2025

Figure S5
Figure S2 from Divergent Clinical and Immunologic Outcomes Based on STK11 Co-mutation Status in Resectable KRAS-Mutant Lung Cancers Following Neoadjuvant Immune Checkpoint Blockade
Authors: Rosner Samuel , Connor Sydney , Sanber Khaled , Zahurak Marianna , Zhang Tianbei , Gurumurthy Isha , Zeng Zhen , Presson Brad , Singh Dipika , Rayes Roni , Sivapalan Lavanya , Pereira Gavin , Ji Zhicheng , Thummalapalli Rohit , Reuss Joshua E. , Broderick Stephen R. , Jones David R. , Deutsch Julie S. , Cottrell Tricia R. , Chaft Jamie E. , Spicer Jonathan , Taube Janis , Anagnostou Valsamo , Brahmer Julie R. , Pardoll Drew M. , Ji Hongkai , Forde Patrick M. , Marrone Kristen A. , Smith Kellie N.
Published: January 2025

Figure S2
Supplementary Table S2 from A Phase II Basket Trial of Dual Anti–CTLA-4 and Anti–PD-1 Blockade in Rare Tumors SWOG S1609: Vulvar Cancers
Authors: Chae Young Kwang , Corthell Lucy , Patel Sandip Pravin , Edwards Robert , Scalici Jennifer M. , Kim Hye Sung , Chung Liam Il-Young , Othus Megan , McLeod Christine M. , Chen Helen X. , Sharon Elad , Streicher Howard , Ryan Christopher W. , Blanke Charles D. , Kurzrock Razelle
Published: January 2025

Representativeness of Study Participants
Data from A Phase III Randomized Trial of Integrated Genomics and Avatar Models for Personalized Treatment of Pancreatic Cancer: The AVATAR Trial
Authors: Sarno Francesca , Tenorio Jair , Perea Sofia , Medina Laura , Pazo-Cid Roberto , Juez Ignacio , Garcia-Carbonero Rocío , Feliu Jaime , Guillen-Ponce Carmen , Lopez-Casas Pedro P. , Guerra Carmen , Duran Yolanda , López-Acosta José Francisco , Alonso Carolina , Esquivel Estrella , Dopazo Ana , Akshinthala Dipikaa , Muthuswamy Senthil K. , Lapunzina Pablo , Bockorny Bruno , Hidalgo Manuel
Published: January 2025

AbstractPurpose:
Pancreatic ductal adenocarcinoma (PDAC) has limited treatment options. We compared the efficacy of comprehensive precision medicine against that of the conventional treatment in PDAC.
Patients and Methods:
We report a phase III trial of advanced PDAC in which patients were randomized (1:2) to a conventional treatment treated at physician’s discretion (arm A) or to precision medicine (arm B). Subjects randomized to arm B underwent a tumor biopsy for whole-exome sequencing and to generate avatar mouse models and patient-derived organoids for phenotypic drug screening, with final treatment recommended by the molecular tumor board. The primary objective was median overall survival (OS).
Results:
A total of 137 patients were enrolled with 125 randomized, 44 to arm A and 81 to arm B. Whole-exome sequencing was performed in 80.3% (65/81) patients of arm B, with potentially actionable mutations detected in 21.5% (14/65). Experimental models were generated in 16/81 patients (19.8%). Second-line treatment was administered to 39 patients in the experimental arm, but only four (10.2%) received personalized treatment, whereas 35 could not receive matched therapy because of rapid clinical deterioration, delays in obtaining study results, or the absence of actionable targets. The median OS was 8.7 and 8.6 months (P = 0.849) and the median progression-free survival was 3.8 and 4.3 months (P = 0.563) for the conventional and experimental arms, respectively. Notably, the four patients who received personalized treatment had a median OS of 19.3 months.
Conclusions:
Personalized medicine was challenging to implement in most patients with PDAC, limiting the interpretation of intention-to-treat analysis. Survival was improved in the subset of patients who did receive matched therapy.
Data from Phase II Trial of Induction Chemotherapy for Advanced Sinonasal Squamous Cell Carcinoma
Authors: Contrera Kevin J. , Ferrarotto Renata , Gunn Brandon , Su Shirley Y. , Kies Merrill S. , Glisson Bonnie S. , Garden Adam S. , Roberts Dianna , Habna Curtis , Hoff Camilla O. , El-Naggar Adel , Williams Michelle D. , Raza Shaan M. , DeMonte Franco , Chen Melissa M. , Chambers Mark S. , Hanna Ehab Y.
Published: January 2025

AbstractPurpose:
Outcomes after primary surgery for advanced sinonasal squamous cell carcinoma (SCC) are poor. We tested whether induction chemotherapy (IC) can improve disease control or organ preservation.
Patients and Methods:
A phase II trial evaluated previously untreated patients with stage II to IV, M0 sinonasal SCC. Patients received IC with docetaxel, cisplatin, and fluorouracil, followed by chemoradiotherapy (CRT) for responders and surgery with adjuvant radiotherapy or CRT for nonresponders. The primary endpoints were overall response rate and locoregional control. Secondary endpoints included progression-free survival (PFS), overall survival (OS), organ preservation, and treatment toxicity.
Results:
Of the 31 patients enrolled between 2008 and 2020, 28 were evaluated for efficacy. Disease was T4a, T4b, and N+ in 57%, 21%, and 36% of patients, respectively. The overall response rate was 82.1%; 17.9% of patients had stable disease, and 0% had progressive disease. Grade 3 and 4 adverse events occurred in 54% and 18% of patients, respectively; there were no grade 5 adverse events. The 2-year locoregional control and PFS rates were 64.3% [95% confidence interval (CI), 40.4–77.6) and 52.4% (95% CI, 32.3–69.0), respectively. The median PFS was 25.8 months. The median OS was 47.4 months, with a 2-year OS rate of 69.4% (95% CI, 44.9–80.4). No survival difference was observed between surgery versus CRT (HR, 1.07; 95% CI, 0.9–3.84). Of patients alive at 2 years, 63% achieved organ preservation, avoiding maxillectomy (38%), craniotomy (13%), or orbital exenteration (38%).
Conclusions:
IC and response-directed local treatment achieved promising disease control and added organ preservation for patients with advanced sinonasal SCC.
Data from A Phase II Open-Label, Randomized Clinical Trial of Atezolizumab with or without Human Recombinant IL-7 (CYT107) in Advanced Urothelial Cancer
Authors: Sweis Randy F. , Chatta Gurkamal S. , Jain Rohit K. , Moon Helen , Delacroix Scott Edward , Fang Alana , D’Amico Leonard , Kask Angela Shaulov , Cheever Martin A. , Fling Steven , Sharon Elad , Lacroix Andreanne , Kaiser Judith C. , Pachynski Russell K. , Yu Evan Y.
Published: January 2025

AbstractPurpose:
Advanced urothelial cancer generally has high mortality despite modern anti–PD-1/L1 antibody–based combinations. Augmenting checkpoint inhibitor–mediated immune responses with lymphocyte growth factors may improve outcomes. We conducted a randomized phase II study (Cancer Immunotherapy Trials Network-14) in 47 patients to explore whether human recombinant IL-7 (CYT107) could be safely combined with PD-L1 inhibition to enhance responses.
Patients and Methods:
Patients with urothelial cancer after platinum chemotherapy were randomized to atezolizumab alone or with CYT107 weekly for four doses. The primary objective was clinical efficacy by the objective response rate (ORR). Secondary objectives included safety, toxicity, and other clinical outcomes. Correlative endpoints included peripheral immunophenotyping and quantification of cytokines.
Results:
CYT107 plus atezolizumab was well-tolerated, without dose-limiting toxicities and lower grade 3 to 4 treatment-related adverse events compared with atezolizumab monotherapy. The ORR was 26.3% for the combination therapy versus 23.8% for atezolizumab alone (P = 0.428). The complete response rate was 10.5% for the combination therapy versus 4.8% for monotherapy. Three patients on combination therapy had responses >21 months versus one with monotherapy. CD4+ and CD8+ T-lymphocyte expansion occurred in patients with response to combination therapy, with the greatest effect in T memory stem cells. Patients who responded to treatment exhibited elevated baseline levels of CCL4 and reduced levels of VEGFA and TNF.
Conclusions:
Combining CYT107 with atezolizumab was safe and resulted in lymphocyte expansion, a doubling of the complete response rate, and durable responses exceeding 2 years. However, the ORR was similar to atezolizumab alone. Increased and sustained doses of CYT107 coupled with patient selection strategies should be further investigated.
Data from Utilizing Patient-Derived Xenografts to Model Precision Oncology for Biliary Tract Cancer
Authors: DiPeri Timothy P. , Evans Kurt W. , Scott Stephen , Zheng Xiaofeng , Varadarajan Kaushik , Kwong Lawrence N. , Kahle Michael , Tran Cao Hop S. , Tzeng Ching-Wei , Vu Thuy , Kim Sunhee , Su Fei , Raso Maria Gabriela , Rizvi Yasmeen , Zhao Ming , Wang Huamin , Lee Sunyoung S. , Yap Timothy A. , Rodon Jordi , Javle Milind , Meric-Bernstam Funda
Published: January 2025

AbstractPurpose:
Biliary tract cancers, which are rare and aggressive malignancies, are rich in clinically actionable molecular alterations. A major challenge in the field is the paucity of clinically relevant biliary tract cancer models that recapitulate the diverse molecular profiles of these tumors. The purpose of this study was to curate a collection of patient-derived xenograft (PDX) models that reflect the spectrum of genomic alterations present in biliary tract cancers to create a resource for modeling precision oncology.
Experimental Design:
PDXs were derived from biliary tract cancer samples collected from surgical resections or metastatic biopsies. Alterations present in the PDXs were identified by whole-exome sequencing and RNA sequencing. PDXs were treated with approved and investigational agents. Efficacy was assessed by change in tumor volume from baseline. Event-free survival was defined as the time to tumor doubling from baseline. Responses were categorized at day 21: >30% decrease in tumor volume = partial response, >20% increase in tumor volume = progressive disease, and any non-partial response/progressive disease was considered stable disease.
Results:
Genomic sequencing demonstrated key actionable alterations across this cohort, including alterations in FGFR2, isocitrate dehydrogenase I, ERRB2, PIK3CA, PTEN, and KRAS. RNA sequencing demonstrated fusions and expression of antibody–drug conjugate targets, including TROP2, HER2, and Nectin4. Therapeutic matching revealed objective responses to approved and investigational agents that have been shown to have antitumor activity clinically.
Conclusions:
In this study, we developed a catalog of biliary tract cancer PDXs that underwent comprehensive molecular profiling and therapeutic modeling. To date, this is one of the largest collections of biliary tract cancer PDX models and will facilitate the development of personalized treatments for patients with these aggressive malignancies.
Data from Divergent Clinical and Immunologic Outcomes Based on STK11 Co-mutation Status in Resectable KRAS-Mutant Lung Cancers Following Neoadjuvant Immune Checkpoint Blockade
Authors: Rosner Samuel , Connor Sydney , Sanber Khaled , Zahurak Marianna , Zhang Tianbei , Gurumurthy Isha , Zeng Zhen , Presson Brad , Singh Dipika , Rayes Roni , Sivapalan Lavanya , Pereira Gavin , Ji Zhicheng , Thummalapalli Rohit , Reuss Joshua E. , Broderick Stephen R. , Jones David R. , Deutsch Julie S. , Cottrell Tricia R. , Chaft Jamie E. , Spicer Jonathan , Taube Janis , Anagnostou Valsamo , Brahmer Julie R. , Pardoll Drew M. , Ji Hongkai , Forde Patrick M. , Marrone Kristen A. , Smith Kellie N.
Published: January 2025

AbstractPurpose:
Co-mutations of the Kirsten rat sarcoma virus (KRAS) and serine/threonine kinase 11 (STK11) genes in advanced non–small cell lung cancer (NSCLC) are associated with immune checkpoint blockade (ICB) resistance. Although neoadjuvant chemoimmunotherapy is now a standard-of-care treatment for resectable NSCLC, the clinical and immunologic impacts of KRAS and STK11 co-mutations in this setting are unknown.
Experimental Design:
We evaluated and compared recurrence-free survival of resectable KRAS-mutated NSCLC tumors, with or without co-occurring STK11 mutations, treated with neoadjuvant ICB. Single-cell transcriptomics was performed on tumor-infiltrating T cells from seven KRASmut/STK11wt tumors and six KRAS and STK11 co-mutated (KRASmut/STK11mut) tumors.
Results:
Relative to KRASmut/STK11wt tumors, KRASmut/STK11mut exhibited significantly higher recurrence risk. Single-cell transcriptomics showed enhanced oxidative phosphorylation with evidence of decreased prostaglandin E2 signaling and increased IL-2 signaling in CD8+ tumor-infiltrating lymphocytes (TIL) from KRASmut/STK11mut tumors, a finding that was mirrored in KRASwt tumors that relapsed. TILs from KRASmut/STK11mut tumors expressed high levels of molecules associated with tumor residence, including CD39 and ZNF683 (HOBIT).
Conclusions:
These divergent T-cell transcriptional fates suggest that T-cell maintenance and residence may be detrimental to antitumor immunity in the context of neoadjuvant ICB for resectable NSCLC, regardless of KRAS mutation status. Our work provides a basis for future investigations into the mechanisms underpinning prostaglandin E2 signaling and IL-2 signaling as they relate to T-cell immunity to cancer and to divergent clinical outcomes in KRASmut/STK11mut NSCLC treated with neoadjuvant ICB.
Data from A Phase II Basket Trial of Dual Anti–CTLA-4 and Anti–PD-1 Blockade in Rare Tumors SWOG S1609: Vulvar Cancers
Authors: Chae Young Kwang , Corthell Lucy , Patel Sandip Pravin , Edwards Robert , Scalici Jennifer M. , Kim Hye Sung , Chung Liam Il-Young , Othus Megan , McLeod Christine M. , Chen Helen X. , Sharon Elad , Streicher Howard , Ryan Christopher W. , Blanke Charles D. , Kurzrock Razelle
Published: January 2025

AbstractPurpose:
Dual PD-1/CTLA-4 inhibition shows promise in various malignancies. The SWOG S1609 Dual Anti–CTLA-4 and Anti–PD-1 Blockade in Rare Tumors (DART) trial presents initial results of ipilimumab/nivolumab in vulvar cancers.
Patients and Methods:
DART is a prospective/open-label/multicenter (1,016 US sites)/multicohort phase II clinical trial of ipilimumab (1 mg/kg intravenously every 6 weeks) plus nivolumab (240 mg intravenously every 2 weeks). The primary endpoint was objective response rate [ORR; confirmed complete response and partial response (PR)] per RECISTv1.1, whereas progression-free survival (PFS), overall survival, clinical benefit rate (CBR; ORR plus stable disease ≥6 months), and toxicity were secondary endpoints.
Results:
Sixteen evaluable patients (median age, 55.5 years; 0–6 prior therapies; no prior immunotherapy) were analyzed, all of whom had squamous cell carcinoma histology. The ORR was 18.8% (3/16), CBR was 25% (4/16), and CBR plus unconfirmed PR rate was 31% (5/16); the PFS was 34.1, 16.7. 15.5, 7.2, and 7.0 months for these five patients, respectively. The median PFS and overall survival were 2.2 and 7.6 months, respectively. The most common adverse events were diarrhea, fatigue, pruritus, anorexia, and nausea (25%, n = 4 each). Grade 3 to 4 adverse events occurred in 25% of patients (n = 4). There was one grade 1 to 2 adverse event (6.7%) that led to discontinuation and one (6.7%) grade 5 death adverse event.
Conclusions:
Ipilimumab plus nivolumab in vulvar cancers resulted in an objective response in 3 of 16 patients, all of whom had durable responses lasting over 1 year. Notably, two additional patients experienced durable stable disease and unconfirmed PR. Correlative studies to determine response and resistance markers are ongoing.
Phase I Study of Adavosertib with Radiotherapy and Temozolomide in Newly Diagnosed Glioblastoma and Intratumoral Drug Levels in Recurrent Glioblastoma
Authors: Lee Eudocia Q. , Alexander Brian M. , Romo Carlos G. , Supko Jeffrey G. , Agar Nathalie Y.R. , Talebi Zahra , Ahluwalia Manmeet S. , Desai Arati S. , Dietrich Jorg , Kaley Thomas J. , Peereboom David M. , Gantchev Jennifer , Baquer Gerard , Santagata Sandro , Takebe Naoko , Desideri Serena , Fisher Joy D. , Sims Megan , Ye Xiaobu , Ligon Keith L. , Nabors Louis B. , Grossman Stuart A. , Wen Patrick Y.
Published: January 2025

Purpose:

Adavosertib is an oral small-molecule inhibitor of Wee1. The Adult Brain Tumor Consortium conducted a phase I study evaluating adavosertib in combination with radiation (RT) and temozolomide (TMZ) in patients with newly diagnosed glioblastoma (GBM), as well as a surgical window-of-opportunity study in recurrent GBM.

Patients and Methods:

The MTD of adavosertib was determined in adult patients with newly diagnosed GBM using a standard 3+3 design in two separate cohorts: with concurrent RT/TMZ or with adjuvant TMZ. A combination cohort with both concurrent and adjuvant adavosertib at MTD followed. We also performed intratumoral drug distribution studies in patients with recurrent GBM undergoing surgery.

Results:

As separate cohorts, the MTD for concurrent adavosertib with RT/TMZ was 200 mg daily Monday through Friday × 6 weeks during RT, and the MTD for adjuvant adavosertib with TMZ was 425 mg daily for 5 days of each 28-day cycle. However, six of 12 patients experienced dose-limiting toxicities (DLT) in the combination cohort. The mean ratios of the intratumoral to plasma concentration of adavosertib were 4.18 ± 3.36 for contrast-enhancing tissue and 0.74 ± 0.63 in nonenhancing tissue.

Conclusions:

Adavosertib at 200 mg daily Monday through Friday × 6 weeks with RT/TMZ and at 425 mg daily on a 5-day/28-day cycle with TMZ had an unacceptable DLT rate. Additional dose levels in combination cohorts resulted in DLT, and we deemed concurrent adavosertib too toxic for further examination. Adavosertib 425 mg daily on a 5-day/28-day cycle with adjuvant TMZ is the recommended phase II dosage. Tissue pharmacokinetics in tissue homogenates and by microdialysis provided complementary information about drug penetration.
Figure S9 from RNA-encoded Interleukin 2 with Extended Bioavailability Amplifies RNA Vaccine–Induced Antitumor T-cell Immunity
Authors: Peters Daniel , Kranz Lena M. , Eisel David , Diken Mustafa , Kreiter Sebastian , Türeci Özlem , Sahin Ugur , Vormehr Mathias
Published: January 2025

Representative dot plots corresponding to flow cytometry data displayed in Figure 4.
Figure S7 from RNA-encoded Interleukin 2 with Extended Bioavailability Amplifies RNA Vaccine–Induced Antitumor T-cell Immunity
Authors: Peters Daniel , Kranz Lena M. , Eisel David , Diken Mustafa , Kreiter Sebastian , Türeci Özlem , Sahin Ugur , Vormehr Mathias
Published: January 2025

Gating strategy for antigen-specific CD8+ T cells, Tregs, and NK cells displayed in Figure 6.
Figure S10 from RNA-encoded Interleukin 2 with Extended Bioavailability Amplifies RNA Vaccine–Induced Antitumor T-cell Immunity
Authors: Peters Daniel , Kranz Lena M. , Eisel David , Diken Mustafa , Kreiter Sebastian , Türeci Özlem , Sahin Ugur , Vormehr Mathias
Published: January 2025

Representative dot plots corresponding to flow cytometry data displayed in Figure 5.
Figure S1 from RNA-encoded Interleukin 2 with Extended Bioavailability Amplifies RNA Vaccine–Induced Antitumor T-cell Immunity
Authors: Peters Daniel , Kranz Lena M. , Eisel David , Diken Mustafa , Kreiter Sebastian , Türeci Özlem , Sahin Ugur , Vormehr Mathias
Published: January 2025

Mouse body weight in response to RNA-LPX and Alb-IL2 RNA-NP or rIL-2. Mouse total body weight after each of three weekly i.v. vaccinations with OVA RNA-LPX combined with one (1x) or five (5x) i.p. injections of rIL-2 or one i.v. injection of Alb-IL2 RNA-NP or Alb RNA-NP in C57BL/6 mice (n=7 mice/group) in per cent of initial mouse body weight. Mean + SEM. Vertical lines indicate treatments (dashed: OVA RNA-LPX + Alb RNA-NP, rIL-2 or Alb-IL2 RNA-NP; dotted: repetitive rIL-2).
Identifying novel inflammatory protein biomarkers and drug targets of inflammatory bowel disease by integrating Mendelian randomization, bioinformatics, and druggability analysis
Authors: Wang Feifan , Chen Lu , Tian Yu
Published: January 2025

Introduction: Inflammatory proteins have the potential to be used as therapeutic targets for inflammatory bowel disease (IBD).
Methods: We conducted Mendelian randomization (MR) analysis to probe causal associations between 91 circulating inflammatory proteins and IBD in the discovery and replication cohorts. Subsequently, we conducted meta-analysis of results from two cohorts. We further conducted protein-protein interaction (PPI), enrichment analysis, and druggability evaluation to elucidate our results and prioritize potential therapeutic targets.
Results: By integrating data from two cohorts, we demonstrated that genetically predicted CD40 (odds ratio [OR] = 0.878, 95% confidence interval [CI] = 0.838-0.919) and C-X-C motif chemokine ligand (CXCL)5 (OR = 0.884, 95%CI = 0.841-0.930) decreased IBD risk. However, genetically predicted CXCL9 (OR = 1.184, 95%CI = 1.084-1.294), Interleukin (IL)-18 (OR = 1.140, 95%CI = 1.076-1.208), CD6 (OR = 1.096, 95%CI = 1.045-1.150), and 4E-binding protein 1 (4E-BP1) (OR = 1.154, 95%CI = 1.070-1.244) increased IBD risk. Moreover, genetically predicted CD40 (OR = 0.855, 95%CI = 0.801-0.912) decreased Crohn’s disease (CD) risk. Genetically predicted fibroblast growth factor 21 (FGF21) (OR = 1.259, 95%CI = 1.135-1.397) and 4E-BP1 (OR = 1.202, 95%CI = 1.088-1.327) increased CD risk. We found no inflammatory protein associated with ulcerative colitis. Additionally, CD was significantly associated with elevated levels of three circulating inflammatory proteins, which are suggested to be the consequences of CD. PPI analysis demonstrated interactions between CXCL5, CXCL9, IL-18, CD40, and FGF21. Enrichment analysis indicated these identified proteins significantly enriched in inflammation-related signaling pathways, including interleukin signaling, cytokine signaling, and NF-κB pathway. Three proteins (CD40, IL-18, 4E-BP1) have been targeted for drug development on cancers and immune-related diseases, with potentials of therapeutic targets for IBD.
Conclusions: Our results provide new biomarkers and drug targets for CD. Moreover, we further demonstrate critical roles of inflammation and immunity in the occurrence and development of IBD.
Worldwide Prevalence of Hereditary Angioedema: A Systematic Review and Meta-Analysis
Authors: Fisch Samuel A. , Rundle Andrew G. , Neugut Alfred I. , Freedberg Daniel E.
Published: January 2025

Introduction:
Hereditary angioedema (HAE) is a rare disease caused by dysfunction or lack of the C1 esterase inhibitor (C1-INH) protein. The true prevalence of HAE, and whether this prevalence differs across regions, is uncertain.

Methods:
To estimate the prevalence of HAE worldwide, a systematic review and meta-analysis was performed. The pooled prevalence of HAE was calculated using a random-effects model, and heterogeneity across studies was assessed.

Results:
Twenty-five studies from 2000 to 2024 were included in the analysis, describing 11,245 cases of HAE. The pooled prevalence of HAE was 1.22 (95% confidence interval (CI): 0.91, 1.53) per 100,000, with lower prevalence reported in Asia and Africa compared to Europe and North America. HAE type 1 made up most of the cases, with a slight female predominance.

Conclusion:
HAE is a rare condition which affects 1-2 individuals per 100,000 population worldwide. A true estimate for the prevalence of HAE will inform care for the condition, especially as new treatment options become available.
REFLECTANCE CONFOCAL MICROSCOPY OF DERMAL PAPILLAE IN HEALTHY SKIN: A HISTOPATHOLOGY CONTROLLED STUDY
Authors: Lacarrubba Francesco , Verzì Anna Elisa , Misciali Cosimo , Domenicali Davide , Micali Giuseppe
Published: January 2025

Introduction. Previous studies have investigated the density of dermal papillae (DP) in normal skin using reflectance confocal microscopy (RCM), a non-invasive imaging technique that allows a real time, high-resolution imaging of the skin, although no histological confirmation was provided. The aim of the present study was to compare the RCM evaluation of DP density in healthy skin with horizontal histopathological sections (HHS), a technique that provides a horizontal view of the skin.
Methods. Ten adult patients were selected, and a healthy skin area was marked for RCM examination and a subsequent 5-mm punch biopsy that was processed for HHS. Two different blinded operators performed DP counting on RCM and HHS images, respectively.
Results. A total of 10 skin samples were obtained from the lower back. The mean DP density resulting from RCM was 84.27±3.24/mm2, while that from HHS was 84.08±2.74/mm2. Student T-test showed no significant differences in DP count between the two techniques (P=0.89).
Discussion. The strength of this study is represented by the histological evaluation which has never been previously performed, whose results align with the RCM findings and validate previous data from our group, with negligible differences. We believe that the exact identification of the DP number in normal skin may have practical implications, as several inflammatory skin conditions are characterized by DP changes such as psoriasis, lichen planus, and discoid lupus.
Intraoperative Rapid On-Site Evaluation of Lung Tumors: A Diagnostic Accuracy Study
Authors: Christofidis Konstantinos , Pergaris Alexandros , Kalfa Maria , Klapsinou Eirini , Kyriakidou Vasiliki , Chodrodimou Zoi , Savvidou Kyriaki , Terzi Maria , Stamou Chrysa , Mallios Dimitrios , Iliadis Kosmas , Salla Charitini , Mikou Panagiota
Published: January 2025

Introduction: Lung cancer remains a major health challenge, and accurate diagnosis is crucial for effective treatment. Rapid on-site evaluation (ROSE) has emerged as a valuable tool in lung cancer diagnosis. This study aims to assess the performance of ROSE in the intraoperative diagnosis of lung cancer and its correlation with the histological findings of frozen sections. Methods: A retrospective review was conducted on 414 cases of intraoperative ROSE performed during lung surgeries between 2017 and 2022. Cytological findings were classified according to the World Health Organization Reporting System for Lung Cytopathology and compared with the subsequent histological diagnoses. Results: ROSE demonstrated a high diagnostic accuracy of 92.2%. The risk of malignancy varied across diagnostic categories, highlighting the value of ROSE in risk stratification. Only 12% of cases with a ROSE diagnosis of malignancy or suspicion of malignancy were discordant with the final histological diagnosis and only as to the specific tumor type. Conclusions: Rapid on-site evaluation is a reliable technique for lung cancer diagnosis, not only during EBUS or CT guided FNA but also in the setting of lung surgery, offering high accuracy and risk stratification. It contributes to improved patient management by optimizing procedures, reducing complications, and enhancing specimen quality for further analyses. ROSE is a valuable asset in the modern era of personalized medicine, facilitating tailored treatment approaches.
Procalcitonin as an early predictive marker for infectious complications after hepatectomy
Authors: Mori Haruki , Maehira Hiromitsu , Nitta Nobuhito , Maekawa Takeru , Ishikawa Hajime , Takebayashi Katsushi , Kaida Sachiko , Miyake Toru , Tani Masaji
Published: January 2025

ABSTRACT
Introduction: The present study aimed to determine the clinical value of serum procalcitonin (PCT) level in predicting postoperative infections after hepatectomy.
Methods: Medical records of 301 consecutive patients who underwent hepatectomy were retrospectively reviewed. We divided the patients into infection-positive and infection-negative groups. We investigated the changes in perioperative inflammatory markers such as C-reactive protein level (CRP) and PCT level. Associations between infectious complications and perioperative inflammatory markers were evaluated to identify predictive factors of infectious complications after hepatectomy.
Results: Postoperative infectious complications occurred in 67 (22.3 %) patients. The areas under the curve (AUCs) using PCT levels on postoperative days (PODs) 1 and 3 were 0.794 and 0.845, respectively, whereas those using CRP were 0.493 and 0.641, respectively. PCT level had a better AUC than CRP for predicting postoperative infectious complications on PODs 1 and 3. Multivariate analysis indicated PCT levels on PODs 1 and 3 were an independent predictor of infectious complications after hepatectomy.
Conclusion: PCT is the only predictive marker for infectious complications after hepatectomy and is valuable for detecting infectious complications from POD 1.
Comparison of genetic mutations of gastric cancer diagnosed before or after H. pylori eradication and between differentiated and undifferentiated types using next-generation sequencing
Authors: Kodama Masaaki , Oda Manami , Mizukami Kazuhiro , Ogawa Ryo , Hirashita Yuka , Fukuda Masahide , Okamoto Kazuhisa , Fukuda Kensuke , Fuchino Takafumi , Ozaka Sotaro , Okimoto Tadayoshi , Abe Hisanori , Inaba Kazumi , Tokoro Masanori , Arita Keiko , Nishikiori Hidefumi , Abe Takashi , Nagai Takayuki , Yamashita Satoshi , Murakami Kazunari
Published: January 2025

Introduction: Genetic abnormalities specific to post-H. pylori eradication gastric cancer (GC), especially those associated with undifferentiated post-eradication GC, are unknown. We conducted next-generation sequencing of GC diagnosed either before or after eradication to investigate the carcinogenesis of post-eradication GC.
Methods: Five cases of post-eradication differentiated GC [HP(-)-D group], five cases of H. pylori-positive differentiated GC [HP(+)-D group], four cases of post-eradication undifferentiated GC [HP(-)-U group)], and six cases of H. pylori-positive undifferentiated GC [HP(+)-U group)] underwent analysis. DNA was extracted from tumor samples, and non-tumor samples of all subjects. Next-generation target sequencing was conducted using the Ion AmpliSeq Library Kit 2.0 with the Ion AmpliSeq Cancer Hotspot Panel v2. Next-generation targeted sequencing results of the cancer part were subtracted from the results of the non-cancer part.
Results: The HP (-)-D group displayed significantly fewer SNPs in hotspot than the other groups (P < 0.01). Definitive DNA mutations were identified by sequencing of cancerous and non-cancerous tissues. 5 of 20 patients had specific somatic mutations, with different TP53 mutations in the HP(+)-D and HP(-)-U groups, CTNNB1 mutations in the HP(+)-U group, and ATM mutations in the HP(+)-U group, but no mutations in the HP(-)-D group.
Conclusion: Several definite genetic mutations involved in GC were observed. Mutations were less frequent in post-eradication differentiated GC. However, because of small number of cases analyzed to identify carcinogenic differences, further analysis with a large number of cases and with strictly grading GC samples is needed.
Biomarkers of RV Dysfunction in HFrEF Identified by Direct Tissue Proteomics: Extracellular Proteins Fibromodulin and Fibulin-5
Authors: Běhounek Matěj , Lipcseyová Denisa , Vít Ondřej , Žáček Petr , Talacko Pavel , Husková Zuzana , Kikerlová Soňa , Tykvartová Tereza , Wohlfahrt Peter , Melenovský Vojtěch , Beneš Jan , Petrák Jiří
Published: January 2025

BACKGROUND:

Right ventricular dysfunction (RVD) is common in patients with heart failure with reduced ejection fraction, and it is associated with poor prognosis. However, no biomarker reflecting RVD is available for routine clinical use.

METHODS:

Proteomic analysis of myocardium from the left ventricle and right ventricle (RV) of patients with heart failure with reduced ejection fraction with (n=10) and without RVD (n=10) who underwent heart transplantation was performed. Concentrations of 2 ECM (extracellular matrix) proteins with the highest myocardial upregulation in RVD, FMOD (fibromodulin) and FBLN5 (fibulin-5), were assayed in the blood and tested in a separate cohort of patients with heart failure with reduced ejection fraction (n=232) to test for the association of the 2 proteins with RV function and long-term outcomes.

RESULTS:

Multivariable linear regression revealed that plasma concentrations of both FMOD and FBLN5 were significantly associated with RV function regardless of the RV function assessment method. No association of FMOD or FBLN5 with left ventricular dysfunction, cardiac index, body mass index, diabetes status, or kidney function was found. Plasma levels of FMOD and FBLN5 were significantly associated with patient outcomes (
P
=0.005;
P
=0.004). Area under the curve analysis showed that the addition of FBLN5 or FMOD to RV function assessment had a significantly higher area under the curve after 4 years of follow-up (0.653 and 0.631, respectively) compared with RV function alone (0.570;
P
<0.05 for both). Similarly, the combination of MAGGIC (Meta-Analysis Global Group in Chronic Heart Failure) score, FBLN5, and FMOD had a significantly larger area under the curve (0.669) than the combination of MAGGIC score+RVD grade (0.572;
P
=0.02). The Kaplan-Meier analysis demonstrated that patients with the elevation of both FMOD and FBLN5 (ie, FMOD >64 ng/mL and FMOD >27 ng/mL) had a worse prognosis than those with the elevation of either FBLN5 or FMOD (
P
=0.03) demonstrating the additive prognostic value of both proteins.

CONCLUSIONS:

Our study proposes that circulating levels of FMOD and FBLN5 may serve as new biomarkers of RVD in patients with heart failure with reduced ejection fraction.
Sound Entities: A Practice in Spatial Composition
Authors: Schnug David
Published: January 2025

This article describes the Sound Entity Creator—a Max abstraction designed for the generation of sound object trajectories for use in electroacoustic spatial composition—and a compositional framework developed for its use. The introductory section addresses issues concerning the use of space in electroacoustic composition and the development of new spatialization technologies. Then the Sound Entity is defined, technical design features of the patches are described, and a compositional framework is presented, which relies on the use of spectral centroid values to generate trajectories typically limited to the surface of a three-dimensional shape. This is followed by examples of the system at work from a composition created by the author. The article concludes with a summary of an expert panel review of the piece that suggests the primary aesthetic goal of the system was achieved.
Learning from Game Live Streaming: A Model for Networked Music Performance
Authors: Peles Goni , Adler Yuval
Published: January 2025

We propose a model of networked music performance to help musicians think through and evaluate their online music productions. First, we utilize a model of game live streaming by T. L. Taylor (2018) to analyze several of our own productions of distanced networked music performances of ludified notation (Peles 2023). Building on Taylor’s model and additional scholarship on music performance, both networked and not, we then extrapolate the insights gained to networked music performance in general and derive a list of key considerations for the analysis, critique, and ideation of networked music performances. Finally, we demonstrate the use of the model through (1) the analysis of a networked music project by other artists, (2) the critique of one of our own recent productions, and (3) the ideation of a potential future performance. Online music production has become an important mode of musicking and continues to grow as a practice. We offer this model as a tool for both practice-based and scholarly work.
Quality Diversity under Sparse Interaction and Sparse Reward: Application to Grasping in Robotics
Authors: Huber Johann , Helenon François , Coninx Miranda , Amar Faïz Ben , Doncieux Stéphane
Published: January 2025

Quality-Diversity (QD) methods are algorithms that aim to generate a set of diverse and highperforming solutions to a given problem. Originally developed for evolutionary robotics, most QD studies are conducted on a limited set of domains'mainly applied to locomotion, where the fitness and the behavior signal are dense. Grasping is a crucial task for manipulation in robotics. Despite the efforts of many research communities, this task is yet to be solved. Grasping cumulates unprecedented challenges in QD literature: it suffers from reward sparsity, behavioral sparsity, and behavior space misalignment. The present work studies how QD can address grasping. Experiments have been conducted on 15 different methods on 10 grasping domains, corresponding to 2 different robot-gripper setups and 5 standard objects. The obtained results show that MAP-Elites variants that select successful solutions in priority outperform all the compared methods on the studied metrics by a large margin. We also found experimental evidence that sparse interaction can lead to deceptive novelty. To our knowledge, the ability to efficiently produce examples of grasping trajectories demonstrated in this work has no precedent in the literature.
Clearing Muddied Waters: The Relationship Between the Rule of Law and the Fight against Corruption in the Jurisprudence of the European Court of Human Rights
Authors: Jelić Ivana , Jungfleisch Julia
Published: January 2025

This paper analyses the nexus between corruption and the rule of law, focusing on the role of international actors in upholding the latter. Special emphasis is placed on asset recovery, including the seizure of property derived from corrupt activities both abroad and within Member States of the Council of Europe and the European Union. The paper focuses on the actions of Member States of the Council of Europe, especially the jurisprudence of the ECtHR and the corresponding international legal framework. The paper concludes with recommendations for fighting corruption while upholding the rule of law for countries in transition and those on their way to European Union accession.