Imperial College London

Dr. David James PINATO

Faculty of MedicineDepartment of Surgery & Cancer

Clinical Reader in Medical Oncology
 
 
 
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Contact

 

+44 (0)20 7594 2799david.pinato Website

 
 
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Location

 

ICTEM buildingHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

505 results found

Trevisani F, Vitale A, Kudo M, Kulik L, Park J-W, Pinato DJ, Cillo Uet al., 2024, Merits and boundaries of the BCLC staging and treatment algorithm: Learning from the past to improve the future with a novel proposal., J Hepatol, Vol: 80, Pages: 661-669

In this Expert Opinion, we thoroughly analyse the Barcelona Clinic Liver Cancer (BCLC) staging and treatment algorithm for hepatocellular carcinoma (HCC) that, since 1999, has standardised HCC management, offering a structured approach for the prognostic evaluation and treatment of patients with HCC. The first part of the article presents the strengths and evolutionary improvements of the BCLC staging system. Nevertheless, both patient characteristics and available treatments have changed in the last two decades, limiting the role of the BCLC criteria for treatment allocation in a growing number of patients. As therapeutic options expand and become more effective, the stage-linked treatment decision-making algorithm may lead to undertreatment and suboptimal outcomes for patients with disease beyond early-stage HCC. Consequently, strict adherence to BCLC criteria is limited in expert centres, particularly for patients diagnosed beyond early-stage HCC. Although the BCLC system remains the benchmark against which other therapeutic frameworks must be judged, the era of precision medicine calls for patient-tailored therapeutic decision-making (by a multidisciplinary tumour board) rather than stage-dictated treatment allocation. Acknowledging this conceptual difference in clinical management, the second part of the article describes a novel "multiparametric therapeutic hierarchy", which integrates a comprehensive assessment of clinical factors, biomarkers, technical feasibility, and resource availability. Lastly, considering the increasing efficacy of locoregional and systemic treatments, the concept of "converse therapeutic hierarchy" is introduced. These treatments can increase the feasibility (conversion approach) and effectiveness (adjuvant approach of systemic therapy) of potentially curative approaches to greatly improve clinical outcomes.

Journal article

Celsa C, Cabibbo G, Pinato DJ, 2024, Reply to: "irLI or Not irLI: That is the Question"., J Hepatol

Journal article

Celsa C, Cabibbo G, Fulgenzi CAM, Scheiner B, D'Alessio A, Manfredi GF, Nishida N, Ang C, Marron TU, Saeed A, Wietharn B, Pinter M, Cheon J, Huang Y-H, Lee P-C, Phen S, Gampa A, Pillai A, Vivaldi C, Salani F, Masi G, Roehlen N, Thimme R, Vogel A, Schönlein M, von Felden J, Schulze K, Wege H, Galle PR, Kudo M, Rimassa L, Singal AG, El Tomb P, Ulahannan S, Parisi A, Chon HJ, Hsu W-F, Stefanini B, Verzoni E, Giusti R, Veccia A, Catino A, Aprile G, Guglielmini PF, Di Napoli M, Ermacora P, Antonuzzo L, Rossi E, Verderame F, Zustovich F, Ficorella C, Di Pietro FR, Battelli N, Negrini G, Grossi F, Bordonaro R, Pipitone S, Banzi M, Ricciardi S, Laera L, Russo A, De Giorgi U, Cavanna L, Sorarù M, Montesarchio V, Bordi P, Brunetti L, Pinto C, Bersanelli M, Cammà C, Cortellini A, Pinato DJet al., 2024, Characteristics and outcomes of immunotherapy-related liver injury in patients with hepatocellular carcinoma versus other advanced solid tumours., J Hepatol, Vol: 80, Pages: 431-442

BACKGROUND & AIMS: Immune-related liver injury (irLI) is commonly observed in patients with cancer treated with immune checkpoint inhibitors (ICIs). We aimed to compare the incidence, clinical characteristics, and outcomes of irLI between patients receiving ICIs for hepatocellular carcinoma (HCC) vs. other solid tumours. METHODS: Two separate cohorts were included: 375 patients with advanced/unresectable HCC, Child-Pugh A class treated with first-line atezolizumab+bevacizumab from the AB-real study, and a non-HCC cohort including 459 patients treated with first-line ICI therapy from the INVIDIa-2 multicentre study. IrLI was defined as a treatment-related increase of aminotransferase levels after exclusion of alternative aetiologies of liver injury. The incidence of irLI was adjusted for the duration of treatment exposure. RESULTS: In patients with HCC, the incidence of any grade irLI was 11.4% over a median treatment exposure of 4.4 months (95% CI 3.7-5.2) vs. 2.6% in the INVIDIa-2 cohort over a median treatment exposure of 12.4 months (95% CI 11.1-14.0). Exposure-adjusted-incidence of any grade irLI was 22.1 per 100-patient-years in patients with HCC and 2.1 per 100-patient-years in patients with other solid tumours (p <0.001), with median time-to-irLI of 1.4 and 4.7 months, respectively. Among patients who developed irLI, systemic corticosteroids were administered in 16.3% of patients with HCC and 75.0% of those without HCC (p <0.001), and irLI resolution was observed in 72.1% and 58.3%, respectively (p = 0.362). In patients with HCC, rates of hepatic decompensation and treatment discontinuation due to irLI were 7%. Grade 1-2 irLI was associated with improved overall survival only in patients with HCC (hazard ratio 0.53, 95% CI 0.29-0.96). CONCLUSIONS: Despite higher incidence and earlier onset, irLI in patients with HCC is characterised by higher rates of remission and lower requirement for corticosteroid therapy (vs. irLI in other solid tumou

Journal article

Pinato DJ, Fulgenzi CAM, D'Alessio A, 2024, Immunotherapy at all stages of hepatocellular carcinoma., Nat Med, Vol: 30, Pages: 640-641

Journal article

Hedayat S, Cascione L, Cunningham D, Schirripa M, Lampis A, Hahne JC, Tunariu N, Hong SP, Marchetti S, Khan K, Fontana E, Angerilli V, Delrieux M, Nava Rodrigues D, Procaccio L, Rao S, Watkins D, Starling N, Chau I, Braconi C, Fotiadis N, Begum R, Guppy N, Howell L, Valenti M, Cribbes S, Kolozsvari B, Kirkin V, Lonardi S, Ghidini M, Passalacqua R, Elghadi R, Magnani L, Pinato DJ, Di Maggio F, Ghelardi F, Sottotetti E, Vetere G, Ciraci P, Vlachogiannis G, Pietrantonio F, Cremolini C, Cortellini A, Loupakis F, Fassan M, Valeri Net al., 2024, Circulating microRNA analysis in a prospective co-clinical trial identifies MIR652-3p as a response biomarker and driver of regorafenib resistance mechanisms in colorectal cancer., Clin Cancer Res

BACKGROUND: The multi-kinase inhibitor regorafenib has demonstrated efficacy in chemo-refractory metastatic colorectal cancer (mCRC) patients. However, lack of predictive biomarkers and concerns over significant toxicities hamper the use of regorafenib in clinical practice. METHODS: Serial liquid biopsies were obtained at baseline and monthly until disease progression in chemo-refractory mCRC patients treated with regorafenib in a phase II clinical trial (PROSPECT-R n=40; NCT03010722) and in a multicentric validation cohort (n=241). Tissue biopsies collected at baseline, after 2 months and at progression in the PROSPECT-R trial were used to establish Patient-Derived Organoids (PDOs) and for molecular analyses. MicroRNA profiling was performed on baseline bloods using the NanoString nCounter platform and results were validated by digital droplet PCR and/or In Situ Hybridization in paired liquid and tissue biopsies. PDOs co-cultures and PDO-xenotransplants were generated for functional analyses. RESULTS: Large-scale microRNA expression analysis in longitudinal matched liquid and tissue biopsies from the PROSPECT-R trial identified MIR652-3p as a biomarker of clinical benefit to regorafenib. These findings were confirmed in an independent validation cohort and in a "control" group of 100 patients treated with lonsurf. Using ex vivo co-culture assays paired with single-cell RNA-sequencing of PDO established pre- and post-treatment, we modelled regorafenib response observed in vivo and in patients, and showed that MIR652-3p controls resistance to regorafenib by impairing regorafenib-induced lethal autophagy and by orchestrating the switch from neo-angiogenesis to vessel co-option. CONCLUSIONS: Our results identify MIR652-3p as potential biomarker and as a driver of cell and non-cell autonomous mechanisms of resistance to regorafenib.

Journal article

Lombardi P, Pinato DJ, 2024, Beyond Time and Space: Charting Dynamic Evolution of Sporadic Colorectal Cancer., Gastroenterology

Journal article

Balcar L, Scheiner B, Fulgenzi CAM, D'Alessio A, Pomej K, Roig MB, Meyer EL, Che J, Nishida N, Lee P-C, Wu L, Ang C, Krall A, Saeed A, Stefanini B, Cammarota A, Pressiani T, Abugabal YI, Chamseddine S, Wietharn B, Parisi A, Huang Y-H, Phen S, Vivaldi C, Salani F, Masi G, Bettinger D, Vogel A, von Felden J, Schulze K, Silletta M, Trauner M, Samson A, Wege H, Piscaglia F, Galle PR, Stauber R, Kudo M, Singal AG, Itani A, Ulahannan SV, Parikh ND, Cortellini A, Kaseb A, Rimassa L, Chon HJ, Pinato DJ, Pinter Met al., 2024, A meta-analysis and real-world cohort study on the sex-related differences in efficacy and safety of immunotherapy for hepatocellular carcinoma., JHEP Rep, Vol: 6

BACKGROUND & AIMS: Sex-related differences in the immune pathogenesis of hepatocellular carcinoma (HCC), particularly related to oestrogen-dependent secretion of pro-tumourigenic cytokines, are well-known. Whether sex influences the efficacy and safety of immunotherapy is not known. METHODS: We performed a restricted maximum likelihood random effects meta-analysis of five phase III trials that evaluated immune checkpoint inhibitors (ICIs) in advanced HCC and reported overall survival (OS) hazard ratios (HRs) stratified by sex to evaluate sex-related differences in OS. In a real-world cohort of 840 patients with HCC from 22 centres included between 2018 and 2023, we directly compared the efficacy and safety of atezolizumab + bevacizumab (A+B) between sexes. Radiological response was reported according to RECIST v1.1. Uni- and multivariable Cox regression analyses were performed for OS and progression-free survival (PFS). RESULTS: In the meta-analysis, immunotherapy was associated with a significant OS benefit only in male (pooled HR 0.79; 95% CI 0.73-0.86) but not in female (pooled HR 0.85; 95% CI 0.70-1.03) patients with HCC. When directly comparing model estimates, no differences in the treatment effect between sexes were observed. Among 840 patients, 677 (81%) were male (mean age 66 ± 11 years), and 163 (19%) were female (mean age 67 ± 12 years). Type and severity of adverse events were similar between the two groups. OS and PFS were comparable between males and females upon uni- and multivariable analyses (aHR for OS and PFS: 0.79, 95% CI 0.59-1.04; 1.02, 95% CI 0.80-1.30, respectively). Objective response rates (24%/22%) and disease control rates (59%/59%) were also similar between sexes. CONCLUSION: Female phase III trial participants experienced smaller OS benefit following ICI therapy for advanced HCC, while outcomes following A+B treatment were comparable between sexes in a large real-world database. Based on the ambiguous sex-related

Journal article

Galle P, Finn RS, Mitchell CR, Ndirangu K, Ramji Z, Redhead GS, Pinato DJet al., 2024, Treatment-emergent antidrug antibodies related to PD-1, PD-L1, or CTLA-4 inhibitors across tumor types: a systematic review., J Immunother Cancer, Vol: 12

BACKGROUND: Increased understanding of how the immune system regulates tumor growth has innovated the use of immunotherapeutics to treat various cancers. The impact of such therapies, including programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors, on the production of antidrug antibodies (ADAs) and their impact on outcomes, is poorly understood. This study aims to evaluate the clinical trial evidence on ADA incidence associated with PD-1, PD-L1, and CTLA-4 inhibitors in the treatment of cancer and to assess associations between treatment administered, ADA incidence, and treatment outcomes. METHODS: Embase®, Medline®, and EBM Reviews were searched via the OVID® platform on February 15, 2022. Conference proceedings, clinical trial registries, and global regulatory and reimbursement body websites were also searched. Eligible publications included clinical trials enrolling patients receiving cancer treatment with either PD-1, PD-L1, or CTLA-4 reporting outcomes including incidence or prevalence of ADAs and the impact of immunogenicity on treatment safety and efficacy. Reference lists of eligible publications were also searched. The review was conducted and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and evidence quality assessment was conducted using the appropriate Joanna Briggs Institute Critical Appraisal tool. RESULTS: After screening 4160 records and reviewing 97 full publications, a total of 34 publications reporting on 68 trials were included. A further 41 relevant clinical trials were identified on ClinicalTrials.gov and a further 32 from searches of packaging inserts. In total, 141 relevant trials covering 15 different checkpoint inhibitors and 16 different tumor types were included. Across the included trials, atezolizumab was associated with the highest incidence of ADAs (29.6% of 639 patients), followed by nivol

Journal article

Agirrezabal I, Bouattour M, Pinato DJ, D'Alessio A, Brennan VK, Carion PL, Shergill S, Amoury N, Vilgrain Vet al., 2024, Efficacy of transarterial radioembolization using Y-90 resin microspheres versus atezolizumab-bevacizumab in unresectable hepatocellular carcinoma: A matching-adjusted indirect comparison., Eur J Cancer, Vol: 196

INTRODUCTION: No head-to-head trials compared the efficacy of transarterial radioembolization (TARE, also known as selective internal radiation therapy) to combination immunotherapy in hepatocellular carcinoma (HCC). The analysis objective was to compare effectiveness outcomes of TARE using Y-90 resin microspheres and atezolizumab-bevacizumab (AB) in advanced unresectable HCC. METHODS: Patient-level data from SARAH randomized controlled trial for TARE and aggregate real-world data from AB-real study were used in an unanchored matching-adjusted indirect comparison. The basecase analysis used per-protocol data from SARAH; intention-to-treat data were used in sensitivity analyses. The following prognostic variables and effect modifiers were identified from literature: cause of disease, macrovascular invasion, Eastern Cooperative Oncology Group Performance Status, alpha-fetoprotein level and albumin-bilirubin score. Weights were assigned to patients from SARAH to balance baseline characteristics across studies and reflect characteristics of AB-real patients. Overall survival (OS), progression-free survival (PFS) and response rates (overall response rates [ORR]) were calculated and compared. RESULTS: The analysis of OS and PFS included 140 patients receiving TARE and 131 for the analysis of response rates, compared to 202 receiving AB. Median OS was 15.0 and 14.9 months for TARE and AB, respectively (HR=0.980; 95% confidence interval [CI]: 0.658-1.461; p-value=0.922). Median PFS was 4.4 and 6.8 months for TARE and AB, respectively (HR=0.745; 95%CI: 0.544-1.022; p-value=0.068). ORR were 19.8% and 25% with TARE and AB, respectively (OR for AB=1.386, 95%CI: 0.746-2.668; p-value=0.306). Sensitivity analyses generated similar results. CONCLUSION: In HCC patients receiving treatment, TARE using Y-90 resin microspheres may achieve comparable effectiveness outcomes compared with AB.

Journal article

Manfredi GF, Pinato DJ, 2024, Inflammation as a Pathogenic Mechanism of Colonic Neoplasia in Primary Sclerosing Cholangitis., Gastroenterology, Vol: 166, Pages: 212-213

Journal article

Taouli B, Ba-Ssalamah A, Chapiro J, Chhatwal J, Fowler K, Kang TW, Knobloch G, Koh D-M, Kudo M, Lee JM, Murakami T, Pinato DJ, Ringe KI, Song B, Tabrizian P, Wang J, Yoon JH, Zeng M, Zhou J, Vilgrain Vet al., 2023, Correction to: Consensus report from the 10th Global Forum for Liver Magnetic Resonance Imaging: developments in HCC management., Eur Radiol

Journal article

Dharmapuri S, Özbek U, Jethra H, Jun T, Marron TU, Saeed A, Huang Y-H, Muzaffar M, Pinter M, Balcar L, Fulgenzi C, Amara S, Weinmann A, Personeni N, Scheiner B, Pressiani T, Navaid M, Bengsch B, Paul S, Khan U, Bettinger D, Nishida N, Mohamed YI, Vogel A, Gampa A, Korolewicz J, Cammarota A, Kaseb A, Galle PR, Pillai A, Wang Y-H, Cortellini A, Kudo M, D'Alessio A, Rimassa L, Pinato DJ, Ang Cet al., 2023, Baseline neutrophil-lymphocyte ratio and platelet-lymphocyte ratio appear predictive of immune treatment related toxicity in hepatocellular carcinoma., World J Gastrointest Oncol, Vol: 15, Pages: 1900-1912, ISSN: 1948-5204

BACKGROUND: A well-recognized class effect of immune checkpoint inhibitors (ICI) is immune-related adverse events (IrAEs) ranging from low grade toxicities to life-threatening end organ damage requiring permanent discontinuation of ICI. Deaths are reported in < 5% of patients treated with ICI. There are, however, no reliable markers to predict the onset and severity of IrAEs. We tested the association between neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) at baseline with development of clinically significant IrAEs (grade ≥ 2) in hepatocellular carcinoma (HCC) patients treated with ICI. AIM: To test the association between NLR and PLR at baseline with development of clinically significant IrAEs (grade ≥ 2) in HCC patients treated with ICI. METHODS: Data was extracted from an international database from a consortium of 11 tertiary-care referral centers. NLR = absolute neutrophil count/absolute lymphocyte count (ALC) and PLR = platelet count/ALC. Cutoff of 5 was used for NLR and 300 for PLR based on literature. We also tested the association between antibiotic and steroid exposure to IrAEs. RESULTS: Data was collected from 361 patients treated between 2016-2020 across the United States (67%), Asia (14%) and Europe (19%). Most patients received Nivolumab (n = 255, 71%). One hundred sixty-seven (46%) patients developed at least one IrAE, highest grade 1 in 80 (48%), grade ≥ 2 in 87 (52%) patients. In a univariable regression model PLR > 300 was significantly associated with a lower incidence of grade ≥ 2 IrAEs (OR = 0.40; P = 0.044). Similarly, a trend was observed between NLR > 5 and lower incidence of grade ≥ 2 IrAEs (OR = 0.58; P = 0.097). Multivariate analyses confirmed PLR > 300 as an independent predictive marker of grade ≥ 2 IrAEs (OR = 0.26; P = 0.011), in addition to treatment with programmed cell death ligand 1 (PD-1)/cytotoxic T lymphocyte-associated protein-4 (OR = 2.57; P = 0.037) and PD-1/tyrosine kinase

Journal article

Joerg V, Scheiner B, D'Alessio A, Fulgenzi CAM, Schoenlein M, Kocheise L, Lohse AW, Huber S, Wege H, Kaseb A, Wang Y, Mathew A, Kuang A, Muzaffar M, Abugabal YI, Chamseddine S, Phen S, Cheon J, Lee P-C, Balcar L, Krall A, Ang C, Wu L, Saeed A, Huang Y-H, Bengsch B, Rimassa L, Weinmann A, Stauber R, Korolewicz J, Pinter M, Singal AG, Chon HJ, Pinato DJ, Schulze K, von Felden Jet al., 2023, Efficacy and safety of atezolizumab/bevacizumab in patients with HCC after prior systemic therapy: A global, observational study, HEPATOLOGY COMMUNICATIONS, Vol: 7

Journal article

Choucair K, Nebhan C, Cortellini A, Hentzen S, Wang Y, Liu C, Giusti R, Filetti M, Ascierto PA, Vanella V, Galetta D, Catino A, Al-Bzour N, Saeed A, Cavalcante L, Pizzutilo P, Genova C, Bersanelli M, Buti S, Johnson DB, Fulgenzi CAM, Pinato DJ, Radford M, Kim C, Naqash AR, Saeed Aet al., 2023, Characterization of Age-Associated, Neutrophil-to-Lymphocyte Ratio (NLR) and Systemic Immune-Inflammatory Index (SII) as Biomarkers of Inflammation in Geriatric Patients with Cancer Treated with Immune Checkpoint Inhibitors: Impact on Efficacy and Survival., Cancers (Basel), Vol: 15, ISSN: 2072-6694

BACKGROUND: Geriatric patients (≥80 years) are underrepresented in immune checkpoint inhibitor (ICIs) clinical trials. However, their unique biology may affect their response to ICIs. There are currently no established biomarkers of the response to ICIs in adult patients with cancer that can help with patient selection. METHODS: We built a multicenter, international retrospective study of 885 patients (<80 years: n = 417, 47.12%; ≥80 years: n = 468, 52.88%) with different tumor types treated with ICIs between 2011 and 2021 from 11 academic centers in the U.S. and Europe. The main outcome measures were objective response rates (ORR), progression-free survival (PFS) and overall survival (OS) stratified by age and circulating inflammatory levels (neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammatory index (SII)). RESULTS: Patients ≥80 years with low NLR (NLR-L) and SII (SII-L) had significantly higher ORR (vs. high NLR [NLR-H], p < 0.01 and SII-H, p < 0.05, respectively). At median follow-ups (13.03 months), and compared to SII-H, patients with SII-L had significantly longer median PFS and OS in patients <80 (p < 0.001), and ≥80 years (p < 0.001). SII-L was independently associated with longer PFS and OS (HR: 0.61 and 0.62, respectively, p < 0.01). CONCLUSION: Lower inflammation pre-ICI initiation may predict an improved response and survival in geriatric patients with cancer.

Journal article

Cortellini A, D'Alessio A, Pinato DJ, 2023, Diabetes and Immune Checkpoint Inhibitors-Response, CLINICAL CANCER RESEARCH, Vol: 29, Pages: 4017-4018, ISSN: 1078-0432

Journal article

Naqash AR, McCallen JD, Mi E, Iivanainen S, Marie MA, Gramenitskaya D, Clark J, Koivunen JP, Macherla S, Jonnalagadda S, Polsani S, Jiwani RA, Hafiz M, Muzaffar M, Brunetti L, Stroud CRG, Walker PR, Wang K, Chung Y, Ruppin E, Lee S-H, Yang LV, Pinato DJ, Lee JS, Cortellini Aet al., 2023, Increased interleukin-6/C-reactive protein levels are associated with the upregulation of the adenosine pathway and serve as potential markers of therapeutic resistance to immune checkpoint inhibitor-based therapies in non-small cell lung cancer., J Immunother Cancer, Vol: 11

BACKGROUND: Systemic immune activation, hallmarked by C-reactive protein (CRP) and interleukin-6 (IL-6), can modulate antitumor immune responses. In this study, we evaluated the role of IL-6 and CRP in the stratification of patients with non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs). We also interrogated the underlying immunosuppressive mechanisms driven by the IL-6/CRP axis. METHODS: In cohort A (n=308), we estimated the association of baseline CRP with objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) in patients with NSCLC treated with ICIs alone or with chemo-immunotherapy (Chemo-ICI). Baseline tumor bulk RNA sequencing (RNA-seq) of lung adenocarcinomas (LUADs) treated with pembrolizumab (cohort B, n=59) was used to evaluate differential expression of purine metabolism, as well as correlate IL-6 expression with PFS. CODEFACS approach was applied to deconvolve cohort B to characterize the tumor microenvironment by reconstructing the cell-type-specific transcriptome from bulk expression. Using the LUAD cohort from The Cancer Genome Atlas (TCGA) we explored the correlation between IL-6 expression and adenosine gene signatures. In a third cohort (cohort C, n=18), plasma concentrations of CRP, adenosine 2a receptor (A2aR), and IL-6 were measured using ELISA. RESULTS: In cohort A, 67.2% of patients had a baseline CRP≥10 mg/L (CRP-H). Patients with CRP-H achieved shorter OS (8.6 vs 14.8 months; p=0.006), shorter PFS (3.3 vs 6.6 months; p=0.013), and lower ORR (24.7% vs 46.3%; p=0.015). After adjusting for relevant clinical variables, CRP-H was confirmed as an independent predictor of increased risk of death (HR 1.51, 95% CI: 1.09 to 2.11) and lower probability of achieving disease response (OR 0.34, 95% CI: 0.13 to 0.89). In cohort B, RNA-seq analysis demonstrated higher IL-6 expression on tumor cells of non-responders, along with a shorter PFS (p<0.05) and enrichment of the puri

Journal article

Bakaloudi DR, Talukder R, Lin GI, Makrakis D, Diamantopoulos LN, Tripathi N, Agarwal N, Zakopoulou R, Bamias A, Brown JR, Pinato DJ, Korolewicz J, Jindal T, Koshkin VS, Murgić J, Miletić M, Frobe A, Johnson J, Zakharia Y, Drakaki A, Rodriguez-Vida A, Rey-Cárdenas M, Castellano D, Buznego LA, Duran I, Carballeira CC, Barrera RM, Marmorejo D, McKay RR, Stewart T, Gupta S, Ruplin AT, Yu EY, Khaki AR, Grivas Pet al., 2023, Response and Outcomes of Maintenance Avelumab After Platinum-Based Chemotherapy (PBC) in Patients With Advanced Urothelial Carcinoma (aUC): "Real World" Experience., Clin Genitourin Cancer, Vol: 21, Pages: 584-593

BACKGROUND: Platinum-based chemotherapy (PBC) followed by avelumab switch maintenance in nonprogressors is standard first line (1L) treatment for advanced urothelial carcinoma (aUC). We describe clinical features and outcomes in a "real-world' cohort treated with avelumab maintenance for aUC. MATERIALS AND METHODS: This was a retrospective cohort study of patients (pts) who received 1L switch maintenance avelumab after no progression on PBC for aUC. We calculated progression-free survival (PFS) and overall survival (OS) from initiation of maintenance avelumab. We also described OS and PFS for specific subsets using Cox regression and observed response rate (ORR). RESULTS: A total of 108 pts with aUC from 14 sites treated with maintenance avelumab were included. There was a median of 6 weeks1-30 from end of PBC to avelumab initiation; median follow-up time from avelumab initiation was 8.8 months (1-42.7). Median [m]PFS was 9.6 months (95%CI 7.5-12.1) and estimated 1-year OS was 72.5%. CR/PR (vs. SD) to 1L PBC (HR = 0.33, 95% CI 0.13-0.87) and ECOG PS 0 (vs. ≥1), (HR = 0.15, 95% CI 0.05-0.47) were associated with longer OS. The presence of liver metastases was associated with shorter PFS (HR = 2.32, 95% CI 1.17-4.59). ORR with avelumab maintenance was 28.7% (complete response 17.6%, partial response 11.1%), 29.6% stable disease, 26.9% progressive disease as best response (14.8% best response unknown). CONCLUSIONS: Results seem relatively consistent with findings from JAVELIN Bladder100 trial and recent "real world" studies. Prior response to platinum-based chemotherapy, ECOG PS 0, and absence of liver metastases were favorable prognostic factors. Limitations include the retrospective design, lack of randomization and central scan review, and possible selection/confounding biases.

Journal article

Scheiner B, Lampichler K, Pomej K, Beer L, Balcar L, Sartoris R, Bouattour M, Sidali S, Trauner M, Mandorfer M, Reiberger T, Scharitzer M, Tamandl D, Pinato DJ, Ronot M, Pinter Met al., 2023, Transversal psoas muscle thickness measurement is associated with response and survival in patients with HCC undergoing immunotherapy, HEPATOLOGY COMMUNICATIONS, Vol: 7

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Pinato DJ, D'Alessio A, Celsa C, Manfredi GF, Fulgenzi CAMet al., 2023, The price and value of therapeutic synergy in liver cancer., Lancet, Vol: 402, Pages: 1108-1110

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Xie E, Yeo YH, Scheiner B, Zhang Y, Hiraoka A, Tantai X, Fessas P, de Castro T, D'Alessio A, Fulgenzi CAM, Xu S, Tsai H-M, Kambhampati S, Wang W, Keenan BP, Gao X, Xing Z, Pinter M, Lin Y-J, Guo Z, Vogel A, Tanaka T, Kuo H-Y, Kelley RK, Kudo M, Yang JD, Pinato DJ, Ji Fet al., 2023, Immune Checkpoint Inhibitors for Child-Pugh Class B Advanced Hepatocellular CarcinomaA Systematic Review and Meta-Analysis, JAMA ONCOLOGY, ISSN: 2374-2437

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Castelo-Branco L, Lee R, Brandao M, Cortellini A, Freitas A, Garassino M, Geukens T, Grivas P, Halabi S, Oliveira J, Pinato DJ, Ribeiro J, Peters S, Pentheroudakis G, Warner JL, Romano Eet al., 2023, Learning lessons from the COVID-19 pandemic for real-world evidence research in oncologydshared perspectives from international consortia, ESMO OPEN, Vol: 8

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Vithayathil M, D'Alessio A, Fulgenzi CAM, Nishida N, Schoenlein M, von Felden J, Schulze K, Wege H, Saeed A, Wietharn B, Hildebrand H, Wu L, Ang C, Marron TU, Weinmann A, Galle PR, Bettinger D, Bengsch B, Vogel A, Balcar L, Scheiner B, Lee P-C, Huang Y-H, Amara S, Muzaffar M, Naqash AR, Cammarota A, Zanuso V, Pressiani T, Pinter M, Cortellini A, Kudo M, Rimassa L, Pinato DJ, Sharma Ret al., 2023, Impact of body mass index in patients receiving atezolizumab plus bevacizumab for hepatocellular carcinoma, HEPATOLOGY INTERNATIONAL, Vol: 17, Pages: 904-914, ISSN: 1936-0533

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Pinter M, Scheiner B, Pinato DJ, 2023, Immune checkpoint inhibitors in hepatocellular carcinoma: emerging challenges in clinical practice, LANCET GASTROENTEROLOGY & HEPATOLOGY, Vol: 8, Pages: 760-770

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Taouli B, Ba-Ssalamah A, Chapiro J, Chhatwal J, Fowler K, Kang TW, Knobloch G, Koh D-M, Kudo M, Lee JM, Murakami T, Pinato DJ, Ringe KI, Song B, Tabrizian P, Wang J, Yoon JH, Zeng M, Zhou J, Vilgrain Vet al., 2023, Consensus report from the 10th Global Forum for Liver Magnetic Resonance Imaging: developments in HCC management, EUROPEAN RADIOLOGY, ISSN: 0938-7994

Journal article

Celsa C, Cabibbo G, Pinato DJ, Di Maria G, Enea M, Vaccaro M, Battaglia S, Rizzo GEM, Giuffrida P, Giacchetto CM, Rancatore G, Grassini MV, Camma Cet al., 2023, Balancing efficacy and tolerability of first-line systemic therapies for advanced hepatocellular carcinoma: a network metanalysis, LIVER CANCER, ISSN: 2235-1795

Journal article

El Zarif T, Nassar AH, Adib E, Fitzgerald BG, Huang J, Mouhieddine TH, Rubinstein PG, Nonato T, McKay RR, Li M, Mittra A, Owen DH, Baiocchi RA, Lorentsen M, Dittus C, Dizman N, Falohun A, Abdel-Wahab N, Diab A, Bankapur A, Reed A, Kim C, Arora A, Shah NJ, El-Am E, Kozaily E, Abdallah W, Al-Hader A, Abu Ghazal B, Saeed A, Drolen C, Lechner MG, Drakaki A, Baena J, Nebhan CA, Haykal T, Morse MA, Cortellini A, Pinato DJ, Dalla Pria A, Hall E, Bakalov V, Bahary N, Rajkumar A, Mangla A, Shah V, Singh P, Nana FA, Lopetegui-Lia N, Dima D, Dobbs RW, Funchain P, Saleem R, Woodford R, Long GV, Menzies AM, Genova C, Barletta G, Puri S, Florou V, Idossa D, Saponara M, Queirolo P, Lamberti G, Addeo A, Bersanelli M, Freeman D, Xie W, Reid EG, Chiao EY, Sharon E, Johnson DB, Ramaswami R, Bower M, Emu B, Marron TU, Choueiri TK, Baden LR, Lurain K, Sonpavde GP, Naqash ARet al., 2023, Safety and Activity of Immune Checkpoint Inhibitors in People Living With HIV and Cancer: A Real-World Report From the Cancer Therapy Using Checkpoint Inhibitors in People Living With HIV-International (CATCH-IT) Consortium, JOURNAL OF CLINICAL ONCOLOGY, Vol: 41, Pages: 3712-+, ISSN: 0732-183X

Journal article

Aboagye E, Lu H, Lou H, Wengert G, Paudel R, Patel N, Desai S, Crum W, Linton-Reid K, Chen M, Li D, Ip J, Mauri F, Pinato DJ, Rockall A, Copley SJ, Ghaem-Maghami Set al., 2023, Tumour and local lymphoid tissue interaction determines prognosis in high grade serous ovarian cancer, Cell Reports Medicine, Vol: 4, Pages: 1-24, ISSN: 2666-3791

Tertiary lymphoid structure (TLS) is associated with prognosis in copy number-driven tumours,including high grade serous ovarian cancer (HGSOC), although the function of TLS and its interactionwith copy-number alterations in HGSOC is not fully understood. In the current study, we confirmthat TLS-high HGSOC patients show significantly better progression free survival. We show thatpresence of TLS in HGSOC tumours is associated with B-cell maturation and cytotoxic tumourspecific T-cells activation and proliferation. Additionally, the copy number loss of IL15 and CXCL10may limit TLS formation in HGSOC; a list of genes that may dysregulate TLS function is also proposed.Manuscript Click here to view linked ReferencesLastly, a radiomics-based signature is developed to predict presence of TLS, which independentlypredicts PFS in both HGSOC patients and ICI-treated NSCLC patients. Overall, we reveal that TLScoordinates intratumoural B-cell and T-cell response against HGSOC tumour, while cancer genomeevolves to counteract TLS formation and function.

Journal article

Cortellini A, D'Alessio A, Cleary S, Buti S, Bersanelli M, Bordi P, Tonini G, Vincenzi B, Tucci M, Russo A, Pantano F, Russano M, Stucci LS, Sergi MC, Falconi M, Zarzana MA, Santini D, Spagnolo F, Tanda ET, Rastelli F, Giorgi FC, Pergolesi F, Giusti R, Filetti M, Lo Bianco F, Marchetti P, Botticelli A, Gelibter A, Siringo M, Ferrari M, Marconcini R, Vitale MG, Nicolardi L, Chiari R, Ghidini M, Nigro O, Grossi F, De Tursi M, Di Marino P, Queirolo P, Bracarda S, Macrini S, Inno A, Zoratto F, Veltri E, Spoto C, Vitale MG, Cannita K, Gennari A, Morganstein DL, Mallardo D, Nibid L, Sabarese G, Brunetti L, Perrone G, Ascierto PA, Ficorella C, Pinato DJet al., 2023, Data from Type 2 Diabetes Mellitus and Efficacy Outcomes from Immune Checkpoint Blockade in Patients with Cancer

<jats:p>&lt;div&gt;AbstractPurpose:&lt;p&gt;No evidence exists as to whether type 2 diabetes mellitus (T2DM) impairs clinical outcome from immune checkpoint inhibitors (ICI) in patients with solid tumors.&lt;/p&gt;Experimental Design:&lt;p&gt;In a large cohort of ICI recipients treated at 21 institutions from June 2014 to June 2020, we studied whether patients on glucose-lowering medications (GLM) for T2DM had shorter overall survival (OS) and progression-free survival (PFS). We used targeted transcriptomics in a subset of patients to explore differences in the tumor microenvironment (TME) of patients with or without diabetes.&lt;/p&gt;Results:&lt;p&gt;A total of 1,395 patients were included. Primary tumors included non–small cell lung cancer (NSCLC; 54.7%), melanoma (24.7%), renal cell (15.0%), and other carcinomas (5.6%). After multivariable analysis, patients on GLM (&lt;i&gt;n&lt;/i&gt; = 226, 16.2%) displayed an increased risk of death [HR, 1.29; 95% confidence interval (CI),1.07–1.56] and disease progression/death (HR, 1.21; 95% CI, 1.03–1.43) independent of number of GLM received. We matched 92 metformin-exposed patients with 363 controls and 78 patients on other oral GLM or insulin with 299 control patients. Exposure to metformin, but not other GLM, was associated with an increased risk of death (HR, 1.53; 95% CI, 1.16–2.03) and disease progression/death (HR, 1.34; 95% CI, 1.04–1.72). Patients with T2DM with higher pretreatment glycemia had higher neutrophil-to-lymphocyte ratio (&lt;i&gt;P&lt;/i&gt; = 0.04), while exploratory tumoral transcriptomic profiling in a subset of patients (&lt;i&gt;n&lt;/i&gt; = 22) revealed differential regulation of innate and adaptive immune pathways in patients with T2DM.&lt;/p&gt;Conclusions:&lt;p&gt;In this study, patients on GLM experienced worse outcomes from immunotherapy, inde

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Cortellini A, D'Alessio A, Cleary S, Buti S, Bersanelli M, Bordi P, Tonini G, Vincenzi B, Tucci M, Russo A, Pantano F, Russano M, Stucci LS, Sergi MC, Falconi M, Zarzana MA, Santini D, Spagnolo F, Tanda ET, Rastelli F, Giorgi FC, Pergolesi F, Giusti R, Filetti M, Lo Bianco F, Marchetti P, Botticelli A, Gelibter A, Siringo M, Ferrari M, Marconcini R, Vitale MG, Nicolardi L, Chiari R, Ghidini M, Nigro O, Grossi F, De Tursi M, Di Marino P, Queirolo P, Bracarda S, Macrini S, Inno A, Zoratto F, Veltri E, Spoto C, Vitale MG, Cannita K, Gennari A, Morganstein DL, Mallardo D, Nibid L, Sabarese G, Brunetti L, Perrone G, Ascierto PA, Ficorella C, Pinato DJet al., 2023, Supplementary Figure S7 from Type 2 Diabetes Mellitus and Efficacy Outcomes from Immune Checkpoint Blockade in Patients with Cancer

<jats:p>&lt;p&gt;A) Heat map of the 770 transcripts analyzed with the Nanostring Pancancer Immune Panel in diabetic samples (n=11) compared with non-diabetic controls (n=11). B) Heat map of selected differently transcripted genes.&lt;/p&gt;</jats:p>

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