Publications
817 results found
Melikhov O, Kruglova T, Lytkina K, et al., 2021, Use of Janus kinase inhibitors in COVID-19: a prospective observational series in 522 individuals, Annals of the Rheumatic Diseases, Vol: 80, Pages: 1245-1246, ISSN: 0003-4967
Zhu L, Wang Z, Stebbing J, et al., 2021, Immunotherapy-related cystitis: case report and review of the literature, OncoTargets and Therapy, Vol: 2021, Pages: 4321-4328, ISSN: 1178-6930
Immune checkpoint inhibitors (ICIs) including anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA4) and anti-programmed death cell protein 1 (anti-PD1) have extended patient survival benefit and revolutionized cancer treatment. As ICIs rely on immune regeneration to eliminate tumor cells, they can also lead to an imbalance of immune reactions often called immune-related adverse events (irAEs). Rare irAEs such as ocular or cardiac toxicity or vasculitis are seen in less than 1% of patients receiving ICIs. Immune-related cystitis remains a rare occurrence. Herein, we describe a patient with extensive-stage small cell lung cancer (SCLC) and a history of syphilis with a complete response to second-line treatment using nivolumab plus paclitaxel who complained of urinary irritation symptoms. At biopsy, we found infiltration of CD3+ and CD8+ lymphocytes in the urothelium. Although there are reports describing immune-related cystitis in cancer patients, our case has comprehensive pathological confirmation and a differentiation diagnosis. In this report, we review other cases to elucidate clinical characteristics and discuss suitable management of this rare irAE.
Stebbing J, Lauschke VM, 2021, JAK inhibitors — More than just glucocorticoids, New England Journal of Medicine, Vol: 385, Pages: 463-465, ISSN: 0028-4793
Malczewska A, Frampton AE, Mato Prado M, et al., 2021, Circulating microRNAs in small-bowel neuroendocrine tumors: a potential tool for diagnosis and assessment of effectiveness of surgical resection, Annals of Surgery, Vol: 274, Pages: e1-e9, ISSN: 0003-4932
OBJECTIVE: To discover serum-based microRNA (miRNA) biomarkers for small-bowel neuroendocrine tumors (SBNET) to help guide clinical decisions. BACKGROUND: MiRNAs are small noncoding RNA molecules implicated in the initiation and progression of many cancers. MiRNAs are remarkably stable in bodily fluids, and can potentially be translated into clinically useful biomarkers. Novel biomarkers are needed in SBNET to determine disease aggressiveness, select patients for treatment, detect early recurrence, and monitor response. METHODS: This study was performed in 3 stages (discovery, validation, and a prospective, longitudinal assessment). Discovery comprised of global profiling of 376 miRNA in sera from SBNET patients (n = 11) versus healthy controls (HCs; n = 3). Up-regulated miRNAs were subsequently validated in additional SBNET (n = 33) and HC sera (n = 14); and then longitudinally after SBNET resection (n = 12), with serial serum sampling (preoperatively day 0; postoperatively at 1 week, 1 month, and 12 months). RESULTS: Four serum miRNAs (miR-125b-5p, -362-5p, -425-5p and -500a-5p) were significantly up-regulated in SBNET (P < 0.05; fold-change >2) based on multiple normalization strategies, and were validated by RT-qPCR. This combination was able to differentiate SBNET from HC with an area under the curve of 0.951. Longitudinal assessment revealed that miR-125b-5p returned towards HC levels at 1 month postoperatively in patients without disease, whereas remaining up-regulated in those with residual disease (RSD). This was also true at 12 months postoperatively. In addition, miR-362-5p appeared up-regulated at 12 months in RSD and recurrent disease (RCD). CONCLUSIONS: Our study represents the largest global profiling of serum miRNAs in SBNET patients, and the first to evaluate ongoing serum miRNA expression changes after surgical resection. Serum miR-125b-5p and miR-362-5p have potential to be used to detect RSD/RCD.
Peng L, Liang W-H, Mu D-G, et al., 2021, First-line treatment options for PD-L1-negative non-small cell lung cancer: a Bayesian network meta-analysis, Front Oncol, Vol: 11, ISSN: 2234-943X
Background: First-line treatment strategies for programmed death-ligand 1 (PD-L1) negative non-small cell lung cancer (NSCLC) patients include chemotherapy and combination with anti-angiogenesis drugs and/or immune checkpoint inhibitor. We conducted a Bayesian network meta-analysis to evaluate the efficacy of these therapeutic options. Methods: We included phase III randomized controlled trials comparing two or more treatments in the first-line setting for NSCLC, including data in PD-L1-negative patients. First-line strategies were compared and ranked based on the effectiveness in terms of overall survival (OS) and progression-free survival (PFS). A rank was assigned to each treatment after Markov Chain Monte Carlo analyses. Results: Fourteen trials involving 14 regimens matched our eligibility criteria. For OS, none of the treatment were significantly more effective than chemotherapy. Nivolumab plus ipilimumab plus chemotherapy was probably the best option based on analysis of the treatment ranking (probability = 30.1%). For PFS, nivolumab plus chemotherapy plus bevacizumab, atezolizumab plus chemotherapy plus bevacizumab, and atezolizumab plus chemotherapy were statistically superior to chemotherapy in pairwise comparison. Nivolumab plus chemotherapy plus bevacizumab was likely to be the preferred option based on the analysis of the treatment ranking (probability = 72.9%). Conclusions: Nivolumab plus chemotherapy, in combination with angiogenesis inhibition or anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), had maximal benefits for NSCLC patient of PD-L1-negative expression. These findings may facilitate individualized treatment strategies. Safety at an individual patient level should be considered in decision making. Further validation is warranted.
Stebbing J, Baranau Y, Baryash V, et al., 2021, Long-term efficacy and safety of CT-P6 versus trastuzumab in patients with HER2-positive early breast cancer: final results from a randomized phase III trial, Breast Cancer Research and Treatment, Vol: 188, Pages: 631-640, ISSN: 0167-6806
PurposeEquivalent efficacy was demonstrated for the biosimilar CT-P6 and trastuzumab following neoadjuvant therapy for patients with human epidermal growth factor receptor-2 (HER2)-positive early breast cancer. Following adjuvant treatment, efficacy and safety were comparable between treatments. We report updated safety and efficacy data after up to 3 years’ follow-up.MethodsFollowing neoadjuvant chemotherapy with CT-P6/trastuzumab, patients underwent surgery and continued receiving adjuvant CT-P6/trastuzumab. The primary endpoint (previously reported) was pathological complete response. Time-to-event analyses (disease-free survival [DFS], progression-free survival [PFS], and overall survival [OS]), study drug-related and cardiac adverse events, and immunogenicity were assessed during post-treatment follow-up.ResultsMost patients entered the follow-up period (CT-P6: 259 [95.6%]; trastuzumab: 269 [96.8%]). After a median follow-up of 38.7 (CT-P6) and 39.6 (trastuzumab) months, medians were not reached for time-to-event parameters; estimated hazard ratios (HRs) and 3-year survival rates were similar between groups. Estimated HRs (95% confidence intervals) for CT-P6 versus trastuzumab were 1.23 (0.78–1.93) for DFS, 1.31 (0.86–2.01) for PFS, and 1.10 (0.57–2.13) for OS (intention-to-treat population). Safety findings were comparable between groups for the overall study and follow-up period, including study drug-related cardiac disorders (CT-P6: 22 [8.1%] patients; trastuzumab: 24 [8.6%] patients [overall]) and decreases in left ventricular ejection fraction. Immunogenicity was similar between groups.ConclusionThe similarity of the time-to-event analyses between CT-P6 and trastuzumab supports the equivalence in terms of efficacy established for the primary endpoint. CT-P6 was well tolerated, with comparable safety and immunogenicity to trastuzumab.ClinicalTrials.gov: NCT02162667 (registered June 13, 2014)
Jin R, Peng L, Shou J, et al., 2021, EGFR-mutated squamous cell lung cancer and its association with outcomes, Frontiers in Oncology, Vol: 11, ISSN: 2234-943X
Background: The therapeutic efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in advanced EGFR-mutant lung squamous cell carcinoma (SCC) patients remains uncertain. Furthermore, the factors underlying the responsiveness have not been fully investigated. We therefore investigated the link between genomic profiles and EGFR-TKI efficacy. Material and Methods: We consecutively enrolled stage IV, EGFR-mutant, and EGFR-TKI-treated patients with SCC. Patients with EGFR wild-type lung SCC and EGFR-mutant lung adenocarcinoma were consecutively enrolled as controls, and next-generation sequencing (NGS) was performed. Results: In total, 28 EGFR-mutant lung SCC, 41 EGFR-mutant lung adenocarcinoma, and 40 EGFR wild-type lung SCC patients were included. Among the patients with EGFR mutations, shorter progression-free survival (PFS) was observed in SCC compared to adenocarcinoma (4.6 vs. 11.0 months, P<0.001). Comparison of the genomic profiles revealed that EGFR-mutant SCC patients had similar mutation characteristics to EGFR-mutant adenocarcinoma patients, but differed from those with EGFR wild-type SCC. Further exploration of EGFR-mutant SCC revealed that mutations in CREBBP (P = 0.005), ZNF217 (P = 0.016), and the Wnt (P = 0.027) pathway were negatively associated with PFS. Mutations in GRM8 (P = 0.025) were associated with improved PFS. Conclusions: EGFR-mutant lung SCC has a worse prognosis than EGFR-mutant adenocarcinoma. Mutations in other genes, such as CREBBP, ZNF217, GRM8, or Wnt that had implications on PFS raise the possibility of understanding mechanisms of resistance to EGFR-TKI in lung SCC, which will aid identification of potential beneficial subgroups of patients with EGFR-mutant SCCs receiving EGFR-TKIs.
Nteliopoulos G, Page K, Hills A, et al., 2021, Comparison of two targeted ultra-deep sequencing technologies for analysis of plasma circulating tumour DNA in endocrine-therapy-resistant breast cancer patients, Breast Cancer Research and Treatment, Vol: 188, Pages: 465-176, ISSN: 0167-6806
PurposeThere is growing interest in the application of circulating tumour DNA (ctDNA) as a sensitive tool for monitoring tumour evolution and guiding targeted therapy in patients with cancer. However, robust comparisons of different platform technologies are still required. Here we compared the InVisionSeq™ ctDNA Assay with the Oncomine™ Breast cfDNA Assay to assess their concordance and feasibility for the detection of mutations in plasma at low (< 0.5%) variant allele fraction (VAF).MethodsNinety-six plasma samples from 50 patients with estrogen receptor (ER)-positive metastatic breast cancer (mBC) were profiled using the InVision Assay. Results were compared to the Oncomine assay in 30 samples from 26 patients, where there was sufficient material and variants were covered by both assays. Longitudinal samples were analysed for 8 patients with endocrine resistance.ResultsWe detected alterations in 59/96 samples from 34/50 patients analysed with the InVision assay, most frequently affecting ESR1, PIK3CA and TP53. Complete or partial concordance was found in 28/30 samples analysed by both assays, and VAF values were highly correlated. Excellent concordance was found for most genes, and most discordant calls occurred at VAF < 1%. In longitudinal samples from progressing patients with endocrine resistance, we detected consistent alterations in sequential samples, most commonly in ESR1 and PIK3CA.ConclusionThis study shows that both ultra-deep next-generation sequencing (NGS) technologies can detect genomic alternations even at low VAFs in plasma samples of mBC patients. The strong agreement of the technologies indicates sufficient reproducibility for clinical use as prognosic and predictive biomarker.
Salmeron Rios S, Mas Romero M, Cortes Zamora EB, et al., 2021, Immunogenicity of the BNT162b2 vaccine in frail or disabled nursing home residents: COVID-A study, JOURNAL OF THE AMERICAN GERIATRICS SOCIETY, Vol: 69, Pages: 1441-1447, ISSN: 0002-8614
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- Citations: 48
Stebbing J, Zhang H, Xu Y, et al., 2021, KSR1 regulates BRCA1 degradation and inhibits breast cancer growth (vol 31, pg 2103, 2015), ONCOGENE, Vol: 40, Pages: 3473-3473, ISSN: 0950-9232
Friend T, Stebbing J, 2021, Profiling circulating tumour cells and cell free DNA together in metastatic colon cancer., British Journal of Cancer, ISSN: 0007-0920
The characterisation of CTCs (circulating tumour cells) and cfDNA (circulating free DNA) by Salvianti et al. highlight critical aspects of these approaches' relative strengths, weaknesses, and interdependencies in this study.
Stebbing J, Zhang H, Xu Y, et al., 2021, KSR1 regulates BRCA1 degradation and inhibits breast cancer growth (vol 34, pg 2103, 2015), ONCOGENE, ISSN: 0950-9232
Balachandran K, Williams J, Bell D, et al., 2021, Breast cancer treatment during the first wave of the COVID-19 pandemic at a UK centre, ESMO Breast Cancer Virtual Congress, Publisher: ELSEVIER, Pages: S94-S94, ISSN: 0923-7534
Page K, Martinson LJ, Hastings RK, et al., 2021, Prevalence of ctDNA in early screen-detected breast cancers using highly sensitive and specific dual molecular barcoded personalised mutation assays., Annals of Oncology, ISSN: 0923-7534
Cilibrasi C, Ditsiou A, Papakyriakou A, et al., 2021, LMTK3 inhibition affects microtubule Stability (vol 20, 53, 2021), MOLECULAR CANCER, Vol: 20
Lenz H-J, Richardson P, Stebbing J, 2021, The Emergence of Baricitinib: A Story of Tortoises Versus Hares, CLINICAL INFECTIOUS DISEASES, Vol: 72, Pages: 1251-1252, ISSN: 1058-4838
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- Citations: 4
Magbanua MJM, Hendrix LH, Hyslop T, et al., 2021, Serial Analysis of Circulating Tumor Cells in Metastatic Breast Cancer Receiving First-Line Chemotherapy, JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, Vol: 113, Pages: 443-452, ISSN: 0027-8874
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- Citations: 14
Cilibrasi C, Ditsiou A, Papakyriakou A, et al., 2021, LMTK3 inhibition affects microtubule stability, Molecular Cancer, Vol: 20, Pages: 1-6, ISSN: 1476-4598
Pallett SJC, Denny S, Patel A, et al., 2021, Point-of-care SARS-CoV-2 serological assays for enhanced case finding in a UK inpatient population., Scientific Reports, Vol: 11, Pages: 1-8, ISSN: 2045-2322
Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic. Case identification is currently made by real-time polymerase chain reaction (PCR) during the acute phase and largely restricted to healthcare laboratories. Serological assays are emerging but independent validation is urgently required to assess their utility. We evaluated five different point-of-care (POC) SARS-CoV-2 antibody test kits against PCR, finding concordance across the assays (n=15). We subsequently tested 200 patients using the OrientGene COVID-19 IgG/IgM Rapid Test Cassette and find a sensitivity of 74% in the early infection period (day 5-9 post symptom onset), with 100% sensitivity not seen until day 13, demonstrating inferiority to PCR testing in the infectious period. Negative rate was 96%, but in validating the serological tests uncovered potential false-negatives from PCR testing late-presenting cases. A positive predictive value (PPV) of 37% in the general population precludes any use for general screening. Where a case definition is applied however, the PPV is substantially improved (95·4%), supporting use of serology testing in carefully targeted, high-risk populations. Larger studies in specific patient cohorts, including those with mild infection are urgently required to inform on the applicability of POC serological assays to help control the spread of SARS-CoV-2 and improve case finding of patients that may experience late complications.
Zhang H, Han H, He T, et al., 2021, Response to Cottu, Bozec, Basse, and Paoletti, Journal of the National Cancer Institute, Vol: 113, Pages: 344-345, ISSN: 0027-8874
Carli G, Cecchi L, Stebbing J, et al., 2021, Is asthma protective against COVID-19?, ALLERGY, Vol: 76, Pages: 866-868, ISSN: 0105-4538
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- Citations: 101
Bhangu A, 2021, Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic, COLORECTAL DISEASE, Vol: 23, Pages: 732-749, ISSN: 1462-8910
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- Citations: 43
Friend T, Stebbing J, 2021, What is the intermediate host species of SARS-CoV-2?, Future Virology, Vol: 16, Pages: 153-156, ISSN: 1746-0794
Cereser B, Tabassum N, Belluz LDB, et al., 2021, Mutational burden of the normal breast during age and pregnancy, San Antonio Breast Cancer Symposium, Publisher: AMER ASSOC CANCER RESEARCH, ISSN: 0008-5472
Janni WJ, Yab TC, Hayes DF, et al., 2021, Clinical utility of repeated circulating tumor cell (CTC) enumeration as early treatment monitoring tool in metastatic breast cancer (MBC) - a global pooled analysis with individual patient data, San Antonio Breast Cancer Virtual Symposium, Publisher: AMER ASSOC CANCER RESEARCH, ISSN: 0008-5472
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- Citations: 2
Zagorac S, de Giorgio A, Dabrowska A, et al., 2021, SCIRT lncRNA restrains tumorigenesis by opposing transcriptional programs of tumor-initiating cells., Cancer Research, Vol: 81, Pages: 580-593, ISSN: 0008-5472
In many tumors, cells transition reversibly between slow-proliferating tumor-initiating cells (TIC) and their differentiated, faster-growing progeny. Yet how transcriptional regulation of cell cycle and self-renewal genes is orchestrated during these conversions remains unclear. In this study, we show that as breast TIC form, a decrease in cell-cycle and increase in self-renewal gene expression is coregulated by SOX2 and EZH2, which colocalize at CpG islands. This pattern was negatively controlled by a novel long non-coding RNA (lncRNA) that we name SCIRT, which was markedly upregulated in tumorspheres but colocalized with and counteracted EZH2 and SOX2 during cell cycle and self-renewal regulation to restrain tumorigenesis. SCIRT specifically interacted with EZH2 to increase EZH2 affinity to FOXM1 without binding the latter. In this manner, SCIRT induced transcription at cell cycle gene promoters by recruiting FOXM1 through EZH2 to antagonize EZH2-mediated effects at target genes. Conversely, on stemness genes, FOXM1 was absent and SCIRT antagonized EZH2 and SOX2 activity, balancing towards repression. These data suggest that the interaction of a lncRNA with EZH2 can alter the affinity of EZH2 for its protein binding partners to regulate cancer cell state transitions.
Tabassum N, Constantin TA, Cereser B, et al., 2021, A cell-cycle signature classifier for pan-cancer analysis (vol 39, pg 6041, 2020), ONCOGENE, Vol: 40, Pages: 1752-1752, ISSN: 0950-9232
Williams J, Stebbing J, 2021, COVID-19 and the risk to cancer patients in China., International Journal of Cancer, Vol: 148, Pages: 265-266, ISSN: 0020-7136
Stebbing J, Nievas GS, Falcone M, et al., 2021, JAK inhibition reduces SARS-CoV-2 liver infectivity and modulates inflammatory responses to reduce morbidity and mortality, Science Advances, Vol: 7, Pages: 1-15, ISSN: 2375-2548
Using AI, we identified baricitinib as having antiviral and anticytokine efficacy. We now show a 71% (95% CI 0.15 to 0.58) mortality benefit in 83 patients with moderate-severe SARS-CoV-2 pneumonia with few drug-induced adverse events, including a large elderly cohort (median age, 81 years). An additional 48 cases with mild-moderate pneumonia recovered uneventfully. Using organotypic 3D cultures of primary human liver cells, we demonstrate that interferon-α2 increases ACE2 expression and SARS-CoV-2 infectivity in parenchymal cells by greater than fivefold. RNA-seq reveals gene response signatures associated with platelet activation, fully inhibited by baricitinib. Using viral load quantifications and superresolution microscopy, we found that baricitinib exerts activity rapidly through the inhibition of host proteins (numb-associated kinases), uniquely among antivirals. This reveals mechanistic actions of a Janus kinase-1/2 inhibitor targeting viral entry, replication, and the cytokine storm and is associated with beneficial outcomes including in severely ill elderly patients, data that incentivize further randomized controlled trials.
Majra D, Benson J, Pitts J, et al., 2021, SARS-CoV-2 (COVID-19) superspreader events, JOURNAL OF INFECTION, Vol: 82, Pages: 36-40, ISSN: 0163-4453
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- Citations: 72
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