270 results found
Cortellini A, Giusti R, Filetti M, et al., 2022, High familial burden of cancer correlates with improved outcome from immunotherapy in patients with NSCLC independent of somatic DNA damage response gene status, Journal of Hematology and Oncology, ISSN: 1756-8722
Colmenero J, Tabrizian P, Bhangui P, et al., 2022, De Novo Malignancy After Liver Transplantation: Risk Assessment, Prevention, and Management-Guidelines From the ILTS-SETH Consensus Conference, TRANSPLANTATION, Vol: 106, Pages: E30-E45, ISSN: 0041-1337
Muhammed A, Fulgenzi CAM, Dharmapuri S, et al., 2021, The Systemic Inflammatory Response Identifies Patients with Adverse Clinical Outcome from Immunotherapy in Hepatocellular Carcinoma., Cancers (Basel), Vol: 14, ISSN: 2072-6694
Systemic inflammation is a hallmark of cancer, and it has a pivotal role in hepatocellular carcinoma (HCC) development and progression. We conducted a retrospective study including 362 patients receiving immune check-point inhibitors (ICIs) across three continents, evaluating the influence of neutrophiles to lymphocytes ratio (NLR), platelets to lymphocytes ratio (PLR), and prognostic nutritional index (PNI) on overall (OS), progression free survival (PFS), and radiologic responses. In our 362 patients treated with immunotherapy, median OS and PFS were 9 and 3.5 months, respectively. Amongst tested inflammatory biomarkers, patients with NLR ≥ 5 had shorter OS (7.7 vs. 17.6 months, p < 0.0001), PFS (2.1 vs. 3.8 months, p = 0.025), and lower objective response rate (ORR) (12% vs. 22%, p = 0.034); similarly, patients with PLR ≥ 300 reported shorter OS (6.4 vs. 16.5 months, p < 0.0001) and PFS (1.8 vs. 3.7 months, p = 0.0006). NLR emerged as independent prognostic factors for OS in univariate and multivariate analysis (HR 1.95, 95%CI 1.45-2.64, p < 0.001; HR 1.73, 95%CI 1.23-2.42, p = 0.002) and PLR remained an independent prognostic factor for both OS and PFS in multivariate analysis (HR 1.60, 95%CI 1.6-2.40, p = 0.020; HR 1.99, 95%CI 1.11-3.49, p = 0.021). Systemic inflammation measured by NLR and PLR is an independent negative prognostic factor in HCC patients undergoing ICI therapy. Further studies are required to understand the biological mechanisms underlying this association and to investigate the predictive significance of circulating inflammatory biomarkers in HCC patients treated with ICIs.
Pinato DJ, Tabernero J, Bower M, et al., 2021, Prevalence and impact of COVID-19 sequelae on treatment and survival of patients with cancer who recovered from SARS-CoV-2 infection: evidence from the OnCovid retrospective, multicentre registry study, LANCET ONCOLOGY, Vol: 22, Pages: 1669-1680, ISSN: 1470-2045
Pinato DJ, Patel M, Scotti L, et al., 2021, Time-Dependent COVID-19 Mortality in Patients With Cancer An Updated Analysis of the OnCovid Registry, JAMA ONCOLOGY, ISSN: 2374-2437
Bellan M, Baricich A, Patrucco F, et al., 2021, Long-term sequelae are highly prevalent one year after hospitalization for severe COVID-19, SCIENTIFIC REPORTS, Vol: 11, ISSN: 2045-2322
Nebhan CA, Cortellini A, Ma W, et al., 2021, Clinical Outcomes and Toxic Effects of Single-Agent Immune Checkpoint Inhibitors Among Patients Aged 80 Years or Older With Cancer A Multicenter International Cohort Study, JAMA ONCOLOGY, Vol: 7, Pages: 1856-1861, ISSN: 2374-2437
Garrigos L, Saura C, Martinez-Vila C, et al., 2021, COVID-19 in breast cancer patients: a subanalysis of the OnCovid registry, THERAPEUTIC ADVANCES IN MEDICAL ONCOLOGY, Vol: 13, ISSN: 1758-8340
Cortellini A, Ricciuti B, Facchinetti F, et al., 2021, Antibiotic-exposed patients with non-small-cell lung cancer preserve efficacy outcomes following first-line chemo-immunotherapy, ANNALS OF ONCOLOGY, Vol: 32, Pages: 1391-1399, ISSN: 0923-7534
Hashimoto A, Sarker D, Reebye V, et al., 2021, Upregulation of C/EBP alpha Inhibits Suppressive Activity of Myeloid Cells and Potentiates Antitumor Response in Mice and Patients with Cancer, CLINICAL CANCER RESEARCH, Vol: 27, Pages: 5961-5978, ISSN: 1078-0432
Pinato DJ, Marron TU, Mishra-Kalyani PS, et al., 2021, Original Research 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, EUROPEAN JOURNAL OF CANCER, Vol: 157, Pages: 140-152, ISSN: 0959-8049
Makrakis D, Talukder R, Diamantopoulos LN, et al., 2021, Association of prior local therapy and outcomes with programmed-death ligand-1 inhibitors in advanced urothelial cancer, BJU INTERNATIONAL, ISSN: 1464-4096
Scheiner B, Pomej K, Kirstein MM, et al., 2021, Prognosis of patients with hepatocellular carcinoma treated with immunotherapy - development and validation of the CRAFITY score., J Hepatol
BACKGROUND & AIMS: Immunotherapy with atezolizumab plus bevacizumab represents the new standard of care in systemic front-line treatment of hepatocellular carcinoma (HCC). However, biomarkers that predict treatment success and survival remain an unmet need. METHODS: Patients with HCC put on PD-(L)1-based immunotherapy were included in a training set (n = 190; 6 European centers) and a validation set (n = 102; 8 European centers). We investigated the prognostic value of baseline variables on overall survival using a Cox model in the training set and developed the easily applicable CRAFITY (CRP and AFP in ImmunoTherapY) score. The score was validated in the independent, external cohort, and evaluated in a cohort of patients treated with sorafenib (n = 204). RESULTS: Baseline serum alpha-fetoprotein ≥100 ng/ml (hazard ratio [HR] 1.7; p = 0.007) and C-reactive protein ≥1 mg/dl (HR, 1.7; p = 0.007) were identified as independent prognostic factors in multivariable analysis and were used to develop the CRAFITY score. Patients who fulfilled no criterion (0 points; CRAFITY-low) had the longest median overall survival (27.6 (95% CI 19.5-35.8) months), followed by those fulfilling 1 criterion (1 point; CRAFITY-intermediate; 11.3 (95% CI 8.0-14.6) months), and patients meeting both criteria (2 points; CRAFITY-high; 6.4 (95% CI 4.8-8.1) months; p <0.001). Additionally, best radiological response (complete response/partial response/stable disease/progressive disease) was significantly better in patients with lower CRAFITY score (CRAFITY-low: 9%/20%/52%/20% vs. CRAFITY-intermediate: 3%/25%/36%/36% vs. CRAFITY-high: 2%/15%/22%/61%; p = 0.003). These results were confirmed in the independent validation set and in different subgroups, including Child-Pugh A and B, performance status 0 and ≥1, and first-line and later lines. In the sorafenib cohort, CRAFITY was associated with survival, but not radiological response. CONCLUSIONS: The CRAF
Fessas P, Naeem M, Pinter M, et al., 2021, Early Antibiotic Exposure Is Not Detrimental to Therapeutic Effect from Immunotherapy in Hepatocellular Carcinoma, LIVER CANCER, ISSN: 2235-1795
Demirtas CO, 'Alessio A, Rimassa L, et al., 2021, ALBI grade: Evidence for an improved model for liver functional estimation in patients with hepatocellular carcinoma, JHEP REPORTS, Vol: 3, ISSN: 2589-5559
Serra C, Cossiga V, Serenari M, et al., 2021, Safety and efficacy of percutaneous radiofrequency ablation for hepatocellular carcinoma: a textbook outcome analysis., HPB (Oxford)
BACKGROUND: The Textbook Outcome (TO) is a quality indicator accounting for both efficacy and safety. Herein, we aimed to assess TO in patients with hepatocellular carcinoma (HCC) undergoing percutaneous radiofrequency ablation (RFA). METHODS: All consecutive patients undergoing RFA for HCC between 2014 and 2020, were included. TO was defined as 1) no post-RFA complications or mortality within 30 days after RFA, 2) no prolonged hospital stay 3) no 30-day readmission and 4) the achievement of a complete response (CR) of the target lesion/s at 1-month. RESULTS: Overall, 50.3% of 376 patients fulfilled all the quality indicators to achieve TO. Probabilities of TO achievement decreased in presence of moderate comorbidities (odds ratio[OR]:0.43; 95%C.I.:0.22-0.80;p=0.008), a performance status of 1 (OR: 0.58;95%C.I.:0.37-0.89; p=0.013), the treatment of 2 nodules (OR: 0.71; 95%C.I.:0.41-0.98; p=0.048) or ≥3 nodules (OR: 0.41; 95%C.I.: 0.22 - 0.78; p = 0.007); the treatment of 2-3cm nodules (OR:0.49;95%C.I.:0.31-0.79;p=0.003) or >3cm nodules (OR: 0.36;95%C.I.:0.18-0.73;p=0.004). Risk-stratification provided TO achievement ranging between 77.9% and 14.3%. Patients with TO also had improved survival (p = 0.028). CONCLUSION: About half of patients get TO from RFA. Stratification by clinical and tumoral characteristic should aid provision of RFA in clinical practice, facilitating patient information and providing reference values for future comparative studies.
Desai A, Mohammed TJ, Duma N, et al., 2021, COVID-19 and Cancer A Review of the Registry-Based Pandemic Response, JAMA ONCOLOGY, Vol: 7, Pages: 1882-1890, ISSN: 2374-2437
Soosaipillai G, Wu A, Dettorre GM, et 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, Vol: 13, Pages: 1-17, 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.
Greten TF, Abou-Alfa GK, Cheng A-L, et al., 2021, Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of hepatocellular carcinoma, JOURNAL FOR IMMUNOTHERAPY OF CANCER, Vol: 9
Pinato DJ, Murray SM, Forner A, et al., 2021, Trans-arterial chemoembolization as a loco-regional inducer of immunogenic cell death in hepatocellular carcinoma: implications for immunotherapy., Publisher: BMJ PUBLISHING GROUP, Pages: S448-S448, ISSN: 0168-8278
Scheiner B, Pomej K, Kirstein MM, et al., 2021, Predicting the outcome of patients with hepatocellular carcinoma treated with immunotherapy - the CRAFITY score, Publisher: SPRINGER WIEN, Pages: 179-179, ISSN: 0043-5325
Cortellini A, Bersanelli M, Pinato JD, et al., 2021, Response to letter entitled: Re: Predictive ability of a drug-based score in advanced non-small cell lung cancer patients receiving first-line immunotherapy, EUROPEAN JOURNAL OF CANCER, Vol: 155, Pages: 315-316, ISSN: 0959-8049
Schettini F, Giuliano M, Lambertini M, et al., 2021, Anthracyclines Strike Back: Rediscovering Non-Pegylated Liposomal Doxorubicin in Current Therapeutic Scenarios of Breast Cancer, CANCERS, Vol: 13
Pinato D, Murray S, Forner A, et 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.
Abdelmalak R, Lythgoe MP, Evans J, et al., 2021, Exploration of novel prognostic markers in grade 3 neuroendocrine neoplasia, Cancers, Vol: 13, Pages: 1-12, ISSN: 2072-6694
Background: High-grade neuroendocrine tumours and carcinomas (NET/NECs) behave aggressively, typically presenting at an advanced stage. Prognosis is poor, with median survival between 5 and 34 months. The mainstay of treatment is palliative systemic therapy. However, therapy carries a risk of toxicity, which can reduce quality of life. Therefore, accurate prognostic scores for risk stratification of patients with high-grade NET/NECs are needed to help guide patient management to decide whether active treatment is likely to improve overall survival (OS). We aimed to compare the prognostic ability of published prognostic scores to predict OS in a cohort of patients with high-grade NET/NECs of any primary site. Methods: Treatment, biochemical and clinicopathological data were collected retrospectively from 77 patients with high-grade NET/NECs across three hospitals between 2016 and 2020. Variables including performance status (PS), Ki-67, age at diagnosis, previous treatment and presence of liver metastases were recorded. Pre-treatment neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio, modified Glasgow prognostic score (mGPS), and gastrointestinal neuroendocrine carcinoma (GI-NEC) score were derived. Univariable and multivariable survival analyses were used to assess prognostic ability. Results: The median age of the cohort was 63 years (range: 31–85); 53% of subjects were female. Grade 3 NETs (G3-NETs) were identified in 32 patients and NECs in 45 patients. The median OS was 13.45 months (range: 0.87–65.37) with no difference observed between G3-NETs and NECs. Univariable analysis revealed that NLR (n = 72, p = 0.049), mGPS (n = 56, p = 0.003), GI-NEC score (n = 27, p = 0.0007) and Ki-67 (n = 66, p = 0.007) were significantly associated with OS. Multivariable analysis confirmed that elevated mGPS (p = 0.046), GI-NEC score (p = 0.036), and Ki-67 (p = 0.02) were independently prognostic for reduced OS across the entire cohort. mGPS was identified
Pardo O, Chrysostomou S, Roy R, et 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.
Alexander J, Ibraheim H, Sheth B, et 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.
Pinato DJ, Fessas P, Sapisochin G, et 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.
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