Imperial College London

Dr. David James PINATO

Faculty of MedicineDepartment of Surgery & Cancer

Clinical Senior Lecturer 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

248 results found

Fulgenzi CAM, Talbot T, Murray SM, Silletta M, Vincenzi B, Cortellini A, Pinato DJet al., 2021, Immunotherapy in Hepatocellular Carcinoma, CURRENT TREATMENT OPTIONS IN ONCOLOGY, Vol: 22, ISSN: 1527-2729

Journal article

Demirtas CO, D'Alessio A, Rimassa L, Sharma R, Pinato DJet al., 2021, ALBI grade: Evidence for an improved model for liver functional estimation in patients with hepatocellular carcinoma., JHEP Rep, Vol: 3

Hepatocellular carcinoma (HCC) usually arises in the context of a chronically damaged liver. Liver functional estimation is of paramount importance in clinical decision making. The Child-Pugh score (CPS) can be used to categorise patients into 3 classes (A to C) based on the severity of liver functional impairment according to 5 parameters (albumin, bilirubin, prothrombin time, presence of ascites and hepatic encephalopathy). The albumin-bilirubin (ALBI) grade has emerged as an alternative, reproducible and objective measure of liver functional reserve in patients with HCC, defining worsening liver impairment across 3 grades (I to III). The ALBI score can identify different subgroups of patients with different prognoses across the diverse Barcelona Clinic Liver Cancer stages and CP classes, making it an appealing clinical predictor. In patients treated with potentially curative approaches (resection, transplantation, radiofrequency ablation, microwave ablation), ALBI grade has been shown to correlate with survival, tumour relapse, and post-hepatectomy liver failure. ALBI grade also predicts survival, toxicity and post-procedural liver failure in patients treated with transarterial chemoembolisation, radioembolisation, external beam radiotherapy as well as multi-kinase inhibitors (sorafenib, lenvatinib, cabozantinib, regorafenib) and immune checkpoint inhibitor therapy. In this review, we summarise the body of evidence surrounding the role of ALBI grade as a biomarker capable of optimising patient selection and therapeutic sequencing in HCC.

Journal article

Pinato DJ, Marron TU, Mishra-Kalyani PS, Gong Y, Wei G, Szafron D, Sharon E, Saeed A, Jun T, Dharmapuri S, Naqash AR, Peeraphatdit T, Gampa A, Wang Y, Khan U, Muzaffar M, Navaid M, Lee CJ, Lee P-C, Bulumulle A, Yu B, Paul S, Nimkar N, Bettinger D, Hildebrand H, Abugabal YI, Pressiani T, Personeni N, D'Alessio A, Kaseb AO, Huang Y-H, Ang C, Schneider J, Pillai A, Rimassa L, Goldberg KB, Pazdur R, Theoret M, Lemery S, Fashoyin-Aje L, Cortellini A, Pelosof Let al., 2021, Treatment-related toxicity and improved outcome from immunotherapy in hepatocellular cancer: Evidence from an FDA pooled analysis of landmark clinical trials with validation from routine practice., Eur J Cancer, Vol: 157, Pages: 140-152

PURPOSE: The development of treatment-related adverse events (trAE) correlates favorably with clinical outcomes in multiple studies of patients receiving immune checkpoint inhibitors (ICI); however, this relationship is undefined in patients with hepatocellular carcinoma (HCC). PATIENTS AND METHODS: We derived a cohort of 406 patients with unresectable/advanced HCC receiving ICI therapy as part of international clinical trials submitted to the US Food and Drug Administration (FDA) in support of marketing applications. We tested whether the development of clinically significant trAE (i.e. graded ≥2, trAE2) predicted improved overall survival (OS), progression-free survival (PFS), and objective response rates (ORR) following ICI. We established an international consortium of 10 tertiary-care referral centres located in Europe (n = 67), United States (US, n = 248) and Asia (n = 42) to validate this association. RESULTS: In the FDA dataset of 406 patients, 325 (80%) with Barcelona Clinic Liver Cancer (BCLC) stage C HCC mostly treated with ICI monotherapy (n = 258, 64%), trAE2 were reported in 228 patients (56.1%). Development of trAE2 was associated with longer OS (16.7 versus 11.2 months) and PFS (5.5 versus 2.2 months) and persisted as an independent predictor of outcome after adjusting for viral aetiology, gender, Child-Pugh class, BCLC stage, AFP levels, ECOG-PS, ICI regimen (mono/combination therapy) and receipt of corticosteroid therapy. In a multi-institutional cohort of 357 patients with similar characteristics mostly treated with ICI monotherapy (n = 304, 85%), the development of trAE2 was associated with longer OS (23.3 versus 12.1 months) and PFS (9.6 versus 3.9 months). TrAE2 were confirmed predictors of improved OS (HR 0.43; 95% CI:0.25-0.75) and PFS (HR 0.48; 95% CI: 0.31-0.75), with multivariable analyses confirming their association with outcome independent of clinicopathologic features of interest. Ad

Journal article

Schettini F, Giuliano M, Lambertini M, Bartsch R, Pinato DJ, Onesti CE, Harbeck N, Lüftner D, Rottey S, van Dam PA, Zaman K, Mustacchi G, Gligorov J, Awada A, Campone M, Wildiers H, Gennari A, Tjan-Heijnen VCG, Cortes J, Locci M, Paris I, Del Mastro L, De Placido S, Martín M, Jerusalem G, Venturini S, Curigliano G, Generali Det al., 2021, Anthracyclines Strike Back: Rediscovering Non-Pegylated Liposomal Doxorubicin in Current Therapeutic Scenarios of Breast Cancer., Cancers (Basel), Vol: 13, ISSN: 2072-6694

Anthracyclines are among the most active chemotherapies (CT) in breast cancer (BC). However, cardiotoxicity is a risk and peculiar side effect that has been limiting their use in clinical practice, especially after the introduction of taxanes. Non-pegylated liposomal doxorubicin (NPLD) has been developed to optimize the toxicity profile induced by anthracyclines, while maintaining its unquestionable therapeutic index, thanks to its delivering characteristics that increase its diffusion in tumor tissues and reduce it in normal tissues. This feature allows NPLD to be safely administered beyond the standard doxorubicin maximum cumulative dose of 450-480 mg/m2. Following three pivotal first-line phase III trials in HER2-negative metastatic BC (MBC), this drug was finally approved in combination with cyclophosphamide in this specific setting. Given the increasing complexity of the therapeutic scenario of HER2-negative MBC, we have carefully revised the most updated literature on the topic and dissected the potential role of NPLD in the evolving therapeutic algorithms.

Journal article

Pinato D, Murray S, Forner A, Kaneko T, Fessas P, Toniutto P, Minguez B, Cacciato V, Avellini C, Diaz A, Boyton R, Altmann D, Goldin R, Akarca A, Marafioti T, Mauri F, Casagrande E, Grillo F, Giannini E, Bhoori S, Mazzaferro Vet al., 2021, Trans-arterial chemoembolization as a loco-regional inducer of immunogenic cell death in hepatocellular carcinoma: implications for immunotherapy., Journal for ImmunoTherapy of Cancer, ISSN: 2051-1426

Background: Modulation of adaptive immunity may underscore the efficacy of TACE. We evaluated the influence of TACE on T-cell function by phenotypic lymphocyte characterization in samples of patients undergoing surgery with (T+) or without (T-) prior-TACE treatment.Methods: We profiled intra-tumoural (IT), peri-tumoural (PT) and non-tumoural background tissue (NT) to evaluate regulatory CD4+/FOXP3+ (T-reg) and immune-exhausted CD8+/PD1+ T-cells across T+ (n=58) and T- (n=61). We performed targeted transcriptomics and T-cell receptor sequencing in a restricted subset of samples (n=24) evaluated in relationship with the expression of actionable drivers of anti-cancer immunity including PD-L1, IDO-1, CTLA-4, Lag-3, Tim-3 and CD163.Results: We analyzed 119 patients resected (n=25, 21%) or transplanted (n=94, 79%) for Child-Pugh A (n=65, 55%) and Barcelona Clinic Liver Cancer stage A (n=92, 77%) HCC. T+ samples displayed lower IT CD4+/FOXP3+ (p=0.006), CD8+ (p=0.002) and CD8+/PD1+ and NT CD8+/PD1+ (p<0.001) compared to T-. Lower IT (p=0.005) and NT CD4+/FOXP3+ (p=0.03) predicted for improved recurrence-free survival. In a subset of samples (n=24), transcriptomic analysis revealed up-regulation of a pro-inflammatory response in T+. T+ samples were enriched for IRF2 expression (p=0.01), an interferon-regulated transcription factor implicated in cancer immune-evasion. T-cell clonality and expression of PD-L1, IDO-1, CTLA-4, Lag-3, Tim-3 and CD163 was similar in T+ versus T-.Conclusions: TACE is associated with lower IT density of immune-exhausted effector cytotoxic and T-regs, with significant up-regulation of pro-inflammatory pathways. This highlights the pleiotropic effects of TACE in modulating the tumour microenvironment and strengthens the rationale for developing immunotherapy alongside TACE.

Journal article

Cortellini A, Ricciuti B, Facchinetti F, Alessi JVM, Venkatraman D, Dall'Olio FG, Cravero P, Vaz VR, Ottaviani D, Majem M, Piedra A, Sullivan I, Lee KA, Lamberti G, Hussain N, Clark J, Bolina A, Barba A, Benitez JC, Gorría T, Mezquita L, Hoton D, Nana FA, Besse B, Awad MM, Pinato DJet al., 2021, Antibiotic-exposed patients with non-small cell lung cancer preserve efficacy outcomes following first-line chemo-immunotherapy., Ann Oncol

INTRODUCTION: Prior antibiotic therapy (pATB) is known to impair efficacy of single agent immune checkpoint inhibitors (ICIs), potentially through the induction of gut-dysbiosis. Whether ATB also affect outcomes to chemo-immunotherapy combinations is still unknown. METHODS: In this international multicentre study, we evaluated the association between pATB, concurrent ATB (cATB) and overall survival (OS), progression-free survival (PFS) and objective response rate (ORR) in patients with non-small cell lung cancer (NSCLC) treated with first-line chemo-immunotherapy at 8 referral institutions. RESULTS: Among 302 patients with stage IV NSCLC, 216 (71.5%) and 61 (20.2%) patients were former and current smokers, respectively. PD-L1 tumour expression in evaluable patients (274, 90.7%) was ≥ 50% in 76 (25.2%), 1-49% in 84 (27.9%) and <1% in 113 (37.5%). Multivariable analysis showed pAT- exposed patients to have similar OS (HR = 1.42 [95%CI: 0.91-2.22]; p = 0.1207) and PFS (HR = 1.12 [95%CI: 0.76-1.63]; p = 0.5552), compared to unexposed patients, regardless of performance status. Similarly, no difference with respect to ORR was found across pATB exposure groups (42.6% vs. 57.4% p=0.1794). No differential effect was found depending on pATB exposure duration (≥ 7 vs < 7 days) and route of administration (intravenous vs oral). Similarly, cATB was not associated with OS (HR = 1.29 [95%CI: 0.91-1.84]; p = 0.149) and PFS (HR = 1.20 [95%CI: 0.89-1.63]; p = 0.222) when evaluated as time-varying covariate in multivariable analysis. CONCLUSIONS: In contrast to what has been reported in patients receiving single-agent ICIs, pATB do not impair clinical outcomes to first-line chemo-immunotherapy of patients with NSCLC. pATB status should integrate currently available clinic-pathologic factors for guiding first-line treatment decisions, whilst there should be no concern in offering cATB during chemo-immunotherapy when needed.

Journal article

Soosaipillai G, Wu A, Dettorre GM, Diamantis N, Chester J, Moss C, Aguilar-Company J, Bower M, Sng C, Salazar R, Brunet J, Jones E, Mesia R, Jackson A, Mukherjee U, Sita-Lumsden A, Segui E, Ottaviani D, Carbo A, Benafif S, Wuerstlein R, Carmona C, Chopra N, Cruz C, Swallow J, Saoudi N, Felip E, Galazi M, Garcia-Fructuoso I, Lee A, Newsom-Davis T, Wong S, Sureda A, Maluquer C, Ruiz-Camps I, Cabirta A, Prat A, Gennari A, Ferrante D, Tabernero J, Russell B, Van Hemelrijck M, Dolly S, Pinato Det al., 2021, Specialist palliative and end-of-life care for patients with cancer and SARS-CoV-2 infection: a European perspective, Therapeutic Advances in Medical Oncology, ISSN: 1758-8340

Background: Specialist palliative care team (SPCT) involvement has been shown to improve symptom control and end-of-life care for patients with cancer, but little is known as to how these have been impacted by the COVID-19 pandemic. Here, we report SPCT involvement during the first wave of the pandemic and compare outcomes for patients with cancer who received and did not receive SPCT input from multiple European cancer centres. Methods: From the OnCovid repository (n=1,318), we analysed cancer patients aged ≥18 diagnosed with COVID-19 between 26th February and 22nd June 2020 who had complete specialist palliative care team (SPCT) data (SPCT+ referred; SPCT- not referred).Results: Of 555 eligible patients, 317 were male (57.1%), with a median age of 70 (IQR 20). At COVID-19 diagnosis, 44.7% were on anti-cancer therapy and 53.3% had >1 co-morbidity. 206 patients received SPCT input for symptom control (80.1%), psychological support (54.4%), and/or advance care planning (51%). SPCT+ patients had more DNACPR orders completed prior to (12.6% vs. 3.7%) and during admission (50% vs 22.1%, P<0.001), with more SPCT+ patients deemed suitable for treatment escalation (50% vs. 22.1%, P<0.001). SPCT involvement was associated with higher discharge rates from hospital for end-of-life care (9.7% vs. 0%, P<0.001). End-of-life anticipatory prescribing was higher in SPCT+ patients, with opioids (96.3% vs. 47.1%) and benzodiazepines (82.9% vs. 41.2%) being used frequently for symptom control.Conclusions: SPCT referral facilitated symptom control, emergency care and discharge planning, as well as high rates of referral for psychological support than previously reported. Our study highlighted the critical need of SPCT for patients with cancer during the pandemic and should inform service planning for this population.

Journal article

Abdelmalak R, Lythgoe MP, Evans J, Flynn M, Waters J, Webb A, Pinato DJ, Sharma Ret al., 2021, Exploration of Novel Prognostic Markers in Grade 3 Neuroendocrine Neoplasia, CANCERS, Vol: 13

Journal article

Pardo O, Chrysostomou S, Roy R, Prischi F, Thamlikitkul L, Chapman KL, Mufti U, Peach R, Ding L, Hancock D, Moore C, Molina-Arcas M, Mauri F, Pinato DJ, Abrahams JM, Ottaviani S, Castellano L, Giamas G, Pascoe J, Moonamale D, Pirrie S, Gaunt C, Billingham L, Steven NM, Cullen M, Hrouda D, Winkler M, Post J, Cohen P, Salpeter SJ, Bar V, Zundelevich A, Golan S, Leibovici D, Lara R, Klug DR, Yaliraki SN, Barahona M, Wang Y, Downward J, Skehel JM, Ali MMU, Seckl MJet al., 2021, Repurposed floxacins targeting RSK4 prevent chemoresistance and metastasis in lung and bladder cancer, Science Translational Medicine, Vol: 13, ISSN: 1946-6234

Lung and bladder cancers are mostly incurable because of the early development of drug resistance and metastatic dissemination. Hence, improved therapies that tackle these two processes are urgently needed to improve clinical outcome. We have identified RSK4 as a promoter of drug resistance and metastasis in lung and bladder cancer cells. Silencing this kinase, through either RNA interference or CRISPR, sensitized tumor cells to chemotherapy and hindered metastasis in vitro and in vivo in a tail vein injection model. Drug screening revealed several floxacin antibiotics as potent RSK4 activation inhibitors, and trovafloxacin reproduced all effects of RSK4 silencing in vitro and in/ex vivo using lung cancer xenograft and genetically engineered mouse models and bladder tumor explants. Through x-ray structure determination and Markov transient and Deuterium exchange analyses, we identified the allosteric binding site and revealed how this compound blocks RSK4 kinase activation through binding to an allosteric site and mimicking a kinase autoinhibitory mechanism involving the RSK4’s hydrophobic motif. Last, we show that patients undergoing chemotherapy and adhering to prophylactic levofloxacin in the large placebo-controlled randomized phase 3 SIGNIFICANT trial had significantly increased (P = 0.048) long-term overall survival times. Hence, we suggest that RSK4 inhibition may represent an effective therapeutic strategy for treating lung and bladder cancer.

Journal article

Alexander J, Ibraheim H, Sheth B, Little J, Khan MS, Richards C, Hunter N, Chauhan D, Ratnakumaran R, McHugh K, Pinato DJ, Nathan P, Choy J, Cursz SM, Furness A, Turajlic S, Pickering L, Larkin J, Teare J, Papa S, Speight A, Powell Net al., 2021, Clinical outcomes of patients with corticosteroid refractory immune checkpoint inhibitor induced enterocolitis treated with infliximab, Journal for ImmunoTherapy of Cancer, Vol: 9, Pages: 1-9, ISSN: 2051-1426

IntroductionImmune Checkpoint Inhibitors (CPI) have changed the treatment landscape for many cancers, but also cause severe inflammatory side effects including enterocolitis. CPI-induced enterocolitis is treated empirically with corticosteroids, and infliximab (IFX) is used in corticosteroid-refractory cases. However, robust outcome data for these patients are scarce. MethodsWe conducted a multi-centre (six cancer centres), cohort study of outcomes in patients treated with IFX for corticosteroid-refractory CPI-induced enterocolitis between 2007 and 2020. The primary outcome was corticosteroid-free clinical remission (CFCR) with CTCAE grade 0 for diarrhoea at 12 weeks after IFX initiation. We also assessed cancer outcomes at one year using RECIST criteria.Results127 patients (73 male; median age 59 years) were treated with IFX for corticosteroid-refractory CPI-induced enterocolitis. Ninety-six (75.6%) patients had diarrhoea CTCAE grade >2 and 115 (90.6%) required hospitalisation for colitis. CFCR was 41.2% at 12 weeks and 50.9% at 26 weeks. In multivariable logistical regression, IFX-resistant enterocolitis was associated with rectal bleeding (OR 0.19; 95% CI 0.04-0.80; p=0.03) and absence of colonic crypt abscesses (OR 2.16; 95% CI 1.13-8.05; p=0.03). Cancer non-progression was significantly more common in patients with IFX-resistant enterocolitis (64.4%) as compared to patients with IFX-responsive enterocolitis (37.5%; p=0.013).ConclusionThis is the largest study to date reporting outcomes of IFX therapy in patients with corticosteroid-refractory CPI-induced enterocolitis. Utilizing pre-defined robust endpoints, we have demonstrated that fewer than half of patients achieved CFCR. Our data also indicate that cancer outcomes may be better in patients developing prolonged and severe inflammatory side effects of CPI-therapy.

Journal article

Hashimoto A, Sarker D, Reebye V, Jarvis S, Sodergren MH, Kossenkov A, Raulf N, Vasara J, Andrikakou P, Meyer T, Huang K-W, Plummer R, Chee CE, Spalding D, Pai M, Pinato DJ, Sharma R, Basu B, Palmer D, Ma Y-T, Habib R, Martirosyan A, Elasri N, Reynaud A, Rossi J, Cobbold M, Habib N, Gabrilovich Det al., 2021, Up-regulation of C/EBP alpha inhibits suppressive activity of myeloid cells and potentiates antitumor response in mice and cancer patients., CANCER RESEARCH, Vol: 81, ISSN: 0008-5472

Journal article

Pinato DJ, Valeri N, Muhammed A, Cortellini Aet al., 2021, Therapeutic targeting of VEGFR2 in HBV-associated hepatocellular carcinoma, LANCET GASTROENTEROLOGY & HEPATOLOGY, Vol: 6, Pages: S15-S16

Journal article

Pinato DJ, Cortellini A, Balcells C, Killmer S, Talbot T, Thomas R, Sayed AA, Allara E, Tait P, Ross P, Young AM, Cole T, Goldin RD, Ward C, Akarca A, Blanco JM, Marafioti T, Keun H, Siskos A, Marchesi J, Bengsch B, Sharma Ret al., 2021, A phase Ib study of pembrolizumab following trans-arterial chemoembolization (TACE) in hepatocellular carcinoma (HCC): PETAL, Publisher: ELSEVIER, Pages: S245-S246, ISSN: 0168-8278

Conference paper

Murray S, Forner A, Kaneko T, Fessas P, Toniutto P, Minguez B, Cacciato V, Avellini C, Diaz A, Boyton RJ, Altmann DM, Goldin RD, Akarca AU, Marafioti T, Mauri FA, Casagrande E, Grillo F, Giannini EG, Bhoori S, Mazzaferro V, Pinato DJet al., 2021, Trans-arterial chemoembolization as a loco-regional inducer of immunogenic cell death in hepatocellular carcinoma: implications for immunotherapy, Publisher: ELSEVIER, Pages: S448-S448, ISSN: 0168-8278

Conference paper

Scheiner B, Pomej K, Kirstein MM, Hucke F, Finkelmeier F, Waidmann O, Schulze K, Koch S, Spahn S, Radu IP, Siebenhuener A, Mertens JC, Rahbari NN, Kuetting F, Waldschmidt D-T, Ebert M, Teufel A, De Dosso S, Pinato DJ, Pressiani T, Meischl T, Balcar L, Mueller C, Reiberger T, Trauner M, Personeni N, Rimassa L, Bitzer M, Trojan J, Weinmann A, Wege H, Dufour J-F, Peck-Radosavljevic M, Vogel A, Pinter Met al., 2021, Predicting the outcome of patients with hepatocellular carcinoma treated with immunotherapy-the CRAFITY score, International Liver Congress, Publisher: ELSEVIER, Pages: S236-S238, ISSN: 0168-8278

Conference paper

Munoz-Martinez S, Sapena V, Forner A, Bruix J, Sanduzzi Zamparelli M, Bouattour M, Guedes Leal CR, Theodoro CF, El-Kassas M, Nault JC, Blaise L, Mocan T, da Fonseca LG, Reeves HL, Alves R, Garcia Juarez I, Varela M, Pinato DJ, Gardini AC, Alvares-da-Silva MR, Gonzalez Santiago J, del Mar Lozano M, Carlos Bandi J, Rimassa L, Sala M, Alqahtani S, Margarita Anders M, Pinero F, Lachenmayer A, Tacke F, Roderburg C, Romero Gomez M, Peck-Radosavljevic M, Cabibbo G, Elvevi A, Guarino M, Callado Franca AV, Villani R, Vergara Gomez M, Acevedo J, Rodriguez de Lope C, Mello V, Perello C, Pascual S, Braconi C, Iavarone M, Reig Met al., 2021, Early SARS-CoV-2-related mortality of liver cancer patients: Cancer stage matters, Publisher: ELSEVIER, Pages: S495-S496, ISSN: 0168-8278

Conference paper

Dettorre GM, Dolly S, Loizidou A, Chester J, Jackson A, Mukherjee U, Zambelli A, Aguilar-Company J, Bower M, Sng CC, Salazar R, Bertuzzi A, Brunet J, Mesia R, Sita-Lumsden A, Segui E, Biello F, Generali D, Grisanti S, Seeva P, Rizzo G, Libertini M, Maconi A, Moss C, Tabernero J, Russell B, Harbeck N, Vincenzi B, Bertulli R, Ottaviani D, Linan R, Marrari A, Carmen Carmona-Garcia M, Chopra N, Tondini C, Mirallas O, Tovazzi V, Fotia V, Andrea Cruz C, Saoudi-Gonzalez N, Felip E, Roque A, Lee AJ, Newsom-Davis T, Patriarca A, Rimassa L, Santoro A, Gennari A, Diamantis N, Pinato DJet al., 2021, The acute phase response identifies cancer patients with adverse outcomes from SARS-CoV-2 infection as quantified by the OnCovid Inflammatory Score., Publisher: AMER ASSOC CANCER RESEARCH, ISSN: 0008-5472

Conference paper

Pinato DJ, Fessas P, Sapisochin G, Marron TUet al., 2021, Perspectives on the neoadjuvant use of immunotherapy in hepatocellular carcinoma, Hepatology, Vol: 74, Pages: 483-490, ISSN: 0270-9139

Immune checkpoint inhibitor (ICI) therapy is an increasingly used treatment modality across the various stages of hepatocellular cancer (HCC). There is currently no standard peri-operative therapy for HCC, despite a high probability of recurrence. Emerging studies in a variety of tumors demonstrate significant pathologic and immune responses to neoadjuvant immunotherapy. Unlike kinase inhibitors and other targeted therapies, which demonstrated no benefit in the adjuvant setting and fail to induce significant responses, ICIs can induce radiologically appreciable reduction in disease burden, which make ICI combinations an appealing downstaging strategy in patients early or locally advanced disease. Additionally, induction of anti-tumor immunity in the pre-operative setting may induce protracted T-cell response that, in the post-operative phase, may be capable of eliminating micro-metastatic disease and prevent future recurrence. In this review, we discuss the rationale and clinical hurdles that underlie optimal integration of immunotherapy in the pre-operative setting, highlighting the positive impact on surgical and oncological outcomes in patients with early-stage HCC.

Journal article

Fessas P, Naeem M, Marron TU, Szafron D, Sharon E, Saeed A, Jun T, Dharmapuri S, Naqash AR, Peeraphatdit T, Gampa A, Wang Y, Khan U, Muzaffar M, Navaid M, Lee C, Lee P-C, Bulumulle A, Yu B, Paul S, Nimkar N, Bettinger D, Hildebrand H, Abugabal YI, Pressiani T, Personeni N, Nishida N, Kudo M, Kaseb A, Huang Y-H, Ang C, Pillai A, Rimassa L, Pinato DJet al., 2021, Early antibiotic exposure delays disease progression following immune checkpoint inhibitor therapy for hepatocellular carcinoma: Evidence from an observational study., Publisher: AMER ASSOC CANCER RESEARCH, ISSN: 0008-5472

Conference paper

Possamai L, Gudd C, Au L, Triantafyllou E, Shum B, Liu T, Nathwani R, Kumar N, Mukherjee S, Dhar A, Woollard K, Yone Y, Pinato D, Thursz M, Goldin R, Gore M, Larkin J, Khamri W, Antoniades C, Turajlic Set al., 2021, Activation and transcriptional profile of monocytes and CD8+ T cells are altered in checkpoint inhibitor-related hepatitis, Journal of Hepatology, Vol: 75, Pages: 177-189, ISSN: 0168-8278

Background & Aims: Checkpoint inhibitor-related hepatitis (CPI-Hep) is an emerging clinical challenge. We aimed to gain insights into the immunopathology of CPI-Hep by comprehensively characterising myeloid and lymphoid subsets.Methods: CPI-treated patients with or without related hepatitis (CPI-Hep; n = 22 and CPI-noHep; n = 7) were recruited. Phenotypic and transcriptional profiling of peripheral immune subsets was performed and compared with 19 healthy controls (HCs). In vitro monocyte-derived macrophages (MoMFs) were assessed for activation and cytokine production. CD163, CCR2, CD68, CD3, CD8 and granzyme B expression was assessed using immunohistochemistry/immunofluorescence (n = 4).Results: A significant total monocyte depletion was observed in CPI-Hep compared with HCs (p = 0.04), along with a proportionate increase in the classical monocyte population (p = 0.0002) and significant upregulation of CCR2, CD163 and downregulation of CCR7. Soluble CD163 levels were significantly elevated in CPI-Hep compared with HCs (p <0.0001). In vitro MoMFs from CPI-Hep showed enhanced production of pro-inflammatory cytokines. CD8+ T cells demonstrated increased perforin, granzyme B, ICOS and HLA-DR expression in CPI-Hep. Transcriptional profiling indicated the presence of activated monocyte and enhanced effector CD8+ T cell populations in CPI-Hep. Immunohistochemistry demonstrated co-localisation of CD8+/granzyme B+ T cells with CD68+CCR2+/CD68+CD163+ macrophages in CPI-Hep liver tissue.Conclusions: CPI-Hep is associated with activation of peripheral monocytes and an enhanced cytotoxic, effector CD8+ T cell phenotype. These changes were reflected by liver inflammation composed of CD163+/CCR2+ macrophages and CD8+ T cells.Lay summary: Some patients who receive immunotherapy for cancer develop liver inflammation, which requires cessation of cancer treatment. Herein, we describe ways in which the white blood cells of patients who develop liver inflammation differ from tho

Journal article

Filetti M, Trapani D, Cortellini A, Cofini V, Necozione S, Pinato DJ, Porzio G, Marchetti P, Giusti Ret al., 2021, Knowledge and attitudes of Italian medical oncologists and palliative care physicians toward medical use of cannabis in cancer care: a national survey, SUPPORTIVE CARE IN CANCER, ISSN: 0941-4355

Journal article

Santini D, Zeppola T, Russano M, Citarella F, Anesi C, Buti S, Tucci M, Russo A, Sergi MC, Adamo V, Stucci LS, Bersanelli M, Mazzaschi G, Spagnolo F, Rastelli F, Giorgi FC, Giusti R, Filetti M, 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, Pala L, Queirolo P, Bracarda S, Macrini S, Gori S, Inno A, Zoratto F, Tanda ET, Mallardo D, Vitale MG, Talbot T, Ascierto PA, Pinato DJ, Ficorella C, Porzio G, Cortellini Aet al., 2021, PD-1/PD-L1 checkpoint inhibitors during late stages of life: an ad-hoc analysis from a large multicenter cohort, JOURNAL OF TRANSLATIONAL MEDICINE, Vol: 19

Journal article

Buti S, Bersanelli M, Perrone F, Bracarda S, Di Maio M, Giusti R, Nigro O, Cortinovis DL, Aerts JGJV, Guaitoli G, Barbieri F, Ferrara MG, Bria E, Grossi F, Bareggi C, Berardi R, Torniai M, Cantini L, Sforza V, Genova C, Chiari R, Rocco D, Della Gravara L, Gori S, De Tursi M, Di Marino P, Mansueto G, Zoratto F, Filetti M, Citarella F, Russano M, Mazzoni F, Garassino MC, De Toma A, Signorelli D, Gelibter A, Siringo M, Follador A, Bisonni R, Tuzi A, Minuti G, Landi L, Ricciardi S, Migliorino MR, Tabbo F, Olmetto E, Metro G, Adamo V, Russo A, Spinelli GP, Banna GL, Addeo A, Friedlaender A, Cannita K, Porzio G, Ficorella C, Carmisciano L, Pinato DJ, Mazzaschi G, Tiseo M, Cortellini Aet al., 2021, Predictive ability of a drug-based score in patients with advanced non-small-cell lung cancer receiving first-line immunotherapy, EUROPEAN JOURNAL OF CANCER, Vol: 150, Pages: 224-231, ISSN: 0959-8049

Journal article

Naqash AR, Kihn-Alarcon AJ, Stavraka C, Kerrigan K, Vareki SM, Pinato DJ, Puri Set al., 2021, The role of gut microbiome in modulating response to immune checkpoint inhibitor therapy in cancer, ANNALS OF TRANSLATIONAL MEDICINE, Vol: 9, ISSN: 2305-5839

Journal article

Dettorre G, Patel M, Cortellini A, Gennari A, Pentheroudakis G, Romano E, Pinato Det al., 2021, The systemic pro-inflammatory response: targeting the dangerous liaison between COVID-19 and cancer, ESMO Open, Vol: 6, ISSN: 2059-7029

Inflammation is an established driver of severe SARS-CoV-2 infection and a mechanism linked to the increased susceptibility to fatal COVID-19 demonstrated by patients with cancer. As patients with cancer exhibit a higher level of inflammation compared to the general patient population, patients with cancer and COVID-19 may uniquely benefit from strategies targeted at overcoming the unrestrained pro-inflammatory response. Targeted and non-targeted anti-inflammatory therapies may prevent end-organ damage in SARS-CoV-2-infected patients with cancer and decrease mortality. Here, we review the clinical role of selective inhibition of pro-inflammatory interleukins, tyrosine kinase modulation, anti-TNF agents, and other non-targeted approaches including corticosteroids in their roles as disease-modulating agents in patients with COVID-19 and cancer. Investigation of these therapeutics in this highly vulnerable patient group is posited to facilitate the development of tailored therapeutics for this patient population, aiding the transition of systemic inflammation from a prognostic domain to a source of therapeutic targets.

Journal article

Openshaw MR, Pinato DJ, Valeri N, 2021, Back from the Brink: EGFR Inhibition in Gastroesophageal Cancer, CLINICAL CANCER RESEARCH, Vol: 27, Pages: 2964-2966, ISSN: 1078-0432

Journal article

Singal AG, Hoshida Y, Pinato DJ, Marrero J, Nault J-C, Paradis V, Tayob N, Sherman M, Lim YS, Feng Z, Lok AS, Rinaudo JA, Srivastava S, Llovet JM, Villanueva Aet al., 2021, International Liver Cancer Association (ILCA) White Paper on Biomarker Development for Hepatocellular Carcinoma, GASTROENTEROLOGY, Vol: 160, Pages: 2572-2584, ISSN: 0016-5085

Journal article

Pinato DJ, Scotti L, Gennari A, Colomba-Blameble E, Dolly S, Loizidou A, Chester J, Mukherjee U, Zambelli A, Aguilar-Company J, Bower M, Galazi M, Salazar R, Bertuzzi A, Brunet J, Mesia R, Sita-Lumsden A, Colomba J, Pommeret F, Segui E, Biello F, Generali D, Grisanti S, Rizzo G, Libertini M, Moss C, Evans JS, Russell B, Wuerstlein R, Vincenzi B, Bertulli R, Ottaviani D, Linan R, Marrari A, Carmona-Garcia MC, Sng CCT, Tondini C, Mirallas O, Tovazzi V, Fotia V, Cruz CA, Saoudi-Gonzalez N, Felip E, Lloveras AR, Lee AJX, Newsom-Davis T, Sharkey R, Chung C, Garcia-Illescas D, Reyes R, Wong YNS, Ferrante D, Marco-Hernandez J, Ruiz-Camps I, Gaidano G, Patriarca A, Sureda A, Martinez-Vila C, de Torre AS, Rimassa L, Chiudinelli L, Franchi M, Krengli M, Santoro A, Prat A, Tabernero J, Hemelrijck MV, Diamantis N, Cortellini Aet al., 2021, Determinants of enhanced vulnerability to coronavirus disease 2019 in UK patients with cancer: a European study, EUROPEAN JOURNAL OF CANCER, Vol: 150, Pages: 190-202, ISSN: 0959-8049

Journal article

Muñoz-Martínez S, Sapena V, Forner A, Nault J-C, Sapisochin G, Rimassa L, Sangro B, Bruix J, Sanduzzi-Zamparelli M, Hołówko W, El Kassas M, Mocan T, Bouattour M, Merle P, Hoogwater FJH, Alqahtani SA, Reeves HL, Pinato DJ, Giorgakis E, Meyer T, Villadsen GE, Wege H, Salati M, Mínguez B, Di Costanzo GG, Roderburg C, Tacke F, Varela M, Galle PR, Alvares-da-Silva MR, Trojan J, Bridgewater J, Cabibbo G, Toso C, Lachenmayer A, Casadei-Gardini A, Toyoda H, Lüdde T, Villani R, Matilla Peña AM, Guedes Leal CR, Ronzoni M, Delgado M, Perelló C, Pascual S, Lledó JL, Argemi J, Basu B, da Fonseca L, Acevedo J, Siebenhüner AR, Braconi C, Meyers BM, Granito A, Sala M, Rodríguez Lope C, Blaise L, Romero-Gómez M, Piñero F, Gomez D, Mello V, Pinheiro Alves RC, França A, Branco F, Brandi G, Pereira G, Coll S, Guarino M, Benítez C, Anders MM, Bandi JC, Vergara M, Calvo M, Peck-Radosavljevic M, García-Juárez I, Cardinale V, Lozano M, Gambato M, Okolicsanyi S, Arraez DM, Elvevi A, Muñoz AE, Lué A, Iavarone M, Reig Met al., 2021, Assessing the impact of COVID-19 on liver cancer management (CERO-19), JHEP Reports, Vol: 3, ISSN: 2589-5559

BACKGROUND: The coronavirus 2019 (COVID-19) pandemic has posed unprecedented challenges to healthcare systems and it may have heavily impacted patients with liver cancer (LC). This project has evaluated if the schedule of LC screening or procedures has been interrupted /delayed because of the COVID-19 pandemic. MATERIAL AND METHODS: An international survey evaluated the impact of COVID-19 pandemic on clinical practice and clinical trials from March 2020 to June 2020, as the first phase of a multicentre, international and observational project. The focus was on patients with hepatocellular carcinoma or intrahepatic cholangiocarcinoma, cared for around the world during the first COVID-19 pandemic wave. RESULTS: Ninety-one centres expressed interest to participate and 76 were included in the analysis, from Europe, South America, North America, Asia and Africa (73.7%, 17.1%, 5.3%, 2.6% and 1.3% per continent, respectively). Eighty-seven per cent of the centres modified their clinical practice: 40.8% the diagnostic procedures, 80.9% the screening program, 50% cancelled curative and/or palliative treatments for LC, and 44.0% cancelled the liver transplantation program. Forty-five out 69 (65.2%) centres in which clinical trials were running modified their treatments in that setting, but 58.1% were able to recruit new patients. The phone call service was modified in 51.4% of centres which had this service prior to COVID-19 pandemic (n=19/37). CONCLUSION: The first wave of the COVID-19 pandemic had a tremendous impact on the routine care of patients with LC. Modifications in screening, diagnostic and treatment algorithms may have significantly impaired the outcome of patients. Ongoing data collection and future analyses will report the benefits and disadvantages of the strategies implemented, aiding future decision making.

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