Imperial College London

ProfessorJustinStebbing

Faculty of MedicineDepartment of Surgery & Cancer

Professor of Cancer Medicine and Oncology
 
 
 
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Contact

 

j.stebbing Website CV

 
 
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Assistant

 

Mrs Maureen Francis +44 (0)20 7594 2793

 
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Location

 

ICTEM buildingHammersmith Campus

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Summary

 

Publications

Publication Type
Year
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801 results found

Ríos SS, Zamora EBC, Céspedes AA, Rizos LR, Sánchez-Jurado PM, Sánchez-Nievas G, Romero MM, Tabernero Sahuquillo MT, Señalada JJB, Romero AM, Nogueras IG, de Dios Estrella Cazalla J, Andrés-Pretel F, Lauschke VM, Stebbing J, Abizanda Pet al., 2021, Immunogenicity after six months of BNT162b2 vaccination in frail or disabled nursing home residents: the COVID-A Study, Journal of the American Geriatrics Society, ISSN: 0002-8614

BACKGROUND: There is incomplete information regarding evolution of antibody titers against SARS-CoV-2 after a two-dose strategy vaccination with BNT162b2, in older adults in long-term care facilities (LTCFs) with frailty, disability or cognitive impairment. We aimed to determine IgG antibody titer loss in old adults in LTCFs. METHODS: Multicenter longitudinal cohort study including 127 residents (90 females, 37 males) with a mean age of 82.7 years (range 65-99) with different frailty and disability profiles in two LTCFs in Albacete, Spain. Residents received 2 doses of BNT162b2 as per label, and antibody levels were determined 1 and 6 months after the second dose. Age, sex, previous history of COVID-19, comorbidity (Charlson index), performance in activities of daily living (Barthel index), frailty (FRAIL instrument), and cognitive status were assessed. RESULTS: The mean antibody titers 1 and 6 months after the second vaccine dose were 32,145 AU/mL (SD 41,206) and 6,182 AU/mL (SD 13,316) respectively. Across all participants, the median antibody titer loss measured 77.6% (IQR 23.8%). Notably, the decline of titers in individuals with pre-vaccination COVID-19 infection was significantly lower than in those without history of SARS-CoV-2 infection (72.2% vs 85.3%; p<.001). The median titer decrease per follow-up day was 0.47% (IQR 0.14%) and only pre-vaccination COVID-19 was associated with lower rate of antibody decline at 6 months (HR 0.17; 95% CI 0.07-0.41; p<.001). Frailty, disability, older age, cognitive impairment, or comorbidity were not associated with the extent of antibody loss. CONCLUSIONS: Older adults in LTCFs experience a rapid loss of antibodies between over the first six months after the second dose of BNT162b2 vaccine. Only pre-vaccination COVID-19 is associated with a slower rate of antibodies decrease. Our data support immunization with a third dose in this vulnerable, high-risk population. This article is protected by copyright. All ri

Journal article

McLean KA, Kamarajah SK, Chaudhry D, Gujjuri RR, Raubenheimer K, Trout I, AlAmeer E, Creagh-Brown B, Harrison EM, Nepogodiev D, Roslani AC, Li E, Pata F, Ramos-De La Medina A, van Ramshorst GH, Sayyed R, Simoes J, Valente DCA, Smart N, Bhangu A, Glasbey JC, Khaw RA, Ahmed W, Akhbari M, Baker D, Borakati A, Mills E, Murray V, Thavayogan R, Yasin I, Glasbey J, Ridley W, Sarrami M, Zhang G, Egoroff N, Pockney P, Richards T, Edwards M, Lee M, Pinkney T, Pearse R, Vohra R, Sohrabi C, Jamieson A, Nguyen M, Rahman A, English C, Tincknell L, Kakodkar P, Kwek I, Punjabi N, Burns J, Varghese S, Erotocritou M, McGuckin S, Vayalapra S, Dominguez E, Moneim J, Bhatia S, Kouli O, Salehi M, Tan HL, Yoong A, Zhu L, Seale B, Nowinka Z, Patel N, Chrisp B, Harris J, Maleyko I, Muneeb F, Gough M, James CE, Skan O, Chowdhury A, Rebuffa N, Khan H, Down B, Fatimah HQ, Siaw-Acheampong K, Benson RA, Bywater E, Dawson BE, Evans JP, Heritage E, Jones CS, Khatri C, Keatley JM, Knight A, Lawday S, Mann HS, Marson EJ, Mckay SC, Mills EC, Pellino G, Picciochi M, Taylor EH, Tiwari A, Simoes JF, Trout IM, Venn ML, Wilkin RJW, Smart NJ, Minaya-Bravo A, Gallo G, Moug S, Di Saverio S, Vallance A, Vimalchandran D, Griffiths EA, Evans RPT, Townend P, Roberts K, McKay S, Isaac J, Satoi S, Edwards J, Coonar AS, Marchbank A, Caruana EJ, Layton GR, Patel A, Brunelli A, Ford S, Desai A, Gronchi A, Fiore M, Almond M, Tirotta F, Dumitra S, Kolias A, Price SJ, Fountain DM, Jenkinson MD, Hutchinson P, Marcus HJ, Piper RJ, Lippa L, Servadei F, Esene I, Freyschlag C, Neville I, Rosseau G, Schaller K, Demetriades AK, Robertson F, Alamri A, Shaw R, Schache AG, Winter SC, Ho M, Nankivell P, Biel JR, Batstone M, Ganly I, Vidya R, Wilkins A, Singh JK, Thekinkattil D, Sundar S, Fotopoulou C, Leung E, Khan T, Chiva L, Sehouli J, Fagotti A, Cohen P, Gutelkin M, Ghebre R, Konney T, Pareja R, Bristow R, Dowdy S, Rajkumar STS, Ng J, Fujiwara K, Stewart GD, Lamb B, Narahari K, McNeill A, Colquhoun A, McGrath J, Bromage S, Baroet al., 2021, Death following pulmonary complications of surgery before and during the SARS-CoV-2 pandemic, BRITISH JOURNAL OF SURGERY, Vol: 108, Pages: 1448-1464, ISSN: 0007-1323

Journal article

Page K, Martinson LJ, Fernandez-Garcia D, Hills A, Gleason KLT, Gray MC, Rushton AJ, Nteliopoulos G, Hastings RK, Goddard K, Ions C, Parmar V, Primrose L, Openshaw MR, Guttery DS, Palmieri C, Ali S, Stebbing J, Coombes RC, Shaw JAet al., 2021, Circulating tumor DNA profiling from breast cancer screening through to metastatic disease, JCO Precision Oncology, Vol: 5, Pages: 1768-1776, ISSN: 2473-4284

PURPOSE: We investigated the utility of the Oncomine Breast cfDNA Assay for detecting circulating tumor DNA (ctDNA) in women from a breast screening population, including healthy women with no abnormality detected by mammogram, and women on follow-up through to advanced breast cancer. MATERIALS AND METHODS: Blood samples were taken from 373 women (127 healthy controls recruited through breast screening, 28 ductal carcinoma in situ, 60 primary breast cancers, 47 primary breast cancer on follow-up, and 111 metastatic breast cancers [MBC]) to recover plasma and germline DNA for analysis with the Oncomine Breast cfDNA Assay on the Ion S5 platform. RESULTS: One hundred sixteen of 373 plasma samples had one or more somatic variants detected across eight of the 10 genes and were called ctDNA-positive; MBC had the highest proportion of ctDNA-positive samples (61; 55%) and healthy controls the lowest (20; 15.7%). ESR1, TP53, and PIK3CA mutations account for 93% of all variants detected and predict poor overall survival in MBC (hazard ratio = 3.461; 95% CI, 1.866 to 6.42; P = .001). Patients with MBC had higher plasma cell-free DNA levels, higher variant allele frequencies, and more polyclonal variants, notably in ESR1 than in all other groups. Only 15 individuals had evidence of potential clonal hematopoiesis of indeterminate potential mutations. CONCLUSION: We were able detect ctDNA across the breast cancer spectrum, notably in MBC where variants in ESR1, TP53, and PIK3CA predicted poor overall survival. The assay could be used to monitor emergence of resistance mutations such as in ESR1 that herald resistance to aromatase inhibitors to tailor adjuvant therapies. However, we suggest caution is needed when interpreting results from a single plasma sample as variants were also detected in a small proportion of HCs.

Journal article

Giamas G, Castellano L, Feng Q, Knippschild U, Jacob J, Thomas RS, Coombes RC, Smith CL, Jiao LR, Stebbing Jet al., 2021, CK1 delta modulates the transcriptional activity of ER alpha via AIB1 in an estrogen-dependent manner and regulates ER alpha-AIB1 interactions (Retraction of Vol 37, Pg 3110, 2009), NUCLEIC ACIDS RESEARCH, Vol: 49, Pages: 12006-12006, ISSN: 0305-1048

Journal article

Peng L, Lu D, Xia Y, Hong S, Selvaggi G, Stebbing J, Sun Y, Liang Fet al., 2021, Efficacy and safety of first-line treatment strategies for anaplastic lymphoma kinase-positive non-small cell lung cancer: a Bayesian network meta-analysis., Front Oncol, Vol: 11, Pages: 1-9, ISSN: 2234-943X

Background: Targeted therapies have led to significant improvement in the management and prognosis of anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC). We performed a network meta-analysis of frontline treatment options of ALK-positive NSCLC to provide clinical guidance. Methods: PubMed, Embase, ClinicalTrials.gov, and international conference databases were searched to identify relevant trials from inception to June 30, 2021. Phase III randomized controlled trials (RCTs) comparing treatments for patients with ALK-positive advanced NSCLC in the first-line setting were included in a Bayesian network meta-analysis. Eligible studies reported at least one of the following clinical outcomes: progression-free survival (PFS), overall survival (OS), risk of the central nervous system (CNS) progression, adverse events (AEs) of grade (G) 3 or higher (G3 AEs), or serious AEs (SAEs). Hazard ratios (HRs) and CI for primary outcome of PFS and secondary outcome of OS and risk of CNS progression were obtained. A multivariate, consistency model, fixed-effects analysis was used in the network meta-analysis. Data on G3 AEs and SAEs were abstracted and meta-analyzed. Risk of bias (RoB) was assessed using the Cochrane Collaboration's tool. Results: Nine RCTs comprising 2,484 patients were included with seven treatments: alectinib, brigatinib, ceritinib, crizotinib, ensartinib, lorlatinib, and chemotherapy. Compared with chemotherapy, ALK-tyrosine kinase inhibitors (TKIs) significantly prolong PFS and reduced risk of CNS progression except for ceritinib. Lorlatinib appears superior at reducing risk of CNS progression. None of the ALK-TKIs have a significantly prolonged OS as compared with chemotherapy. Lorlatinib increases the risk of G3 AEs as compared with alectinib (odds ratio 4.26 [95% CrI 1.22 to 15.53]), while alectinib caused the fewest G3 AEs. Conclusions: Lorlatinib is associated with the highest PFS benefit and lowest risk of CNS progression benefits

Journal article

Peng L, Wang Z, Stebbing J, Yu Zet al., 2021, Novel immunotherapeutic drugs for the treatment of lung cancer., Current Opinion in Oncology, ISSN: 1040-8746

PURPOSE OF REVIEW: Cancer cells evade immune surveillance partly due to the immunosuppressive features of the tumor microenvironment (TME). Currently approved immuno-oncology drugs for the treatment of lung cancer are aimed to inhibit immune checkpoints, such as programmed death protein-1 (PD-1), PD ligand-1 (PD-L1) and cytotoxic T lymphocyte-associated antigen 4. Despite these, researchers are currently racing to create the optimal cancer immunotherapy treatments. RECENT FINDINGS: Novel immunotherapeutic drugs mainly act on activated immune cells and exert their therapeutic effects by enhancing antitumor responses. In this article, we review new therapies for the treatment of lung cancer that enhance T cell priming, remove coinhibitory signals, supply costimulatory signals and condition the TME. SUMMARY: As more immunotherapeutic targets are in studies, designing multimodal strategies to provide greater efficacy with lower toxicity will be necessary.

Journal article

Glasbey J, Ademuyiwa A, Adisa A, AlAmeer E, Arnaud AP, Ayasra F, Azevedo J, Minaya-Bravo A, Costas-Chavarri A, Edwards J, Elhadi M, Fiore M, Fotopoulou C, Gallo G, Ghosh D, Griffiths EA, Harrison E, Hutchinson P, Lawani I, Lawday S, Lederhuber H, Leventoglu S, Li E, Gomes GMA, Mann H, Marson EJ, Martin J, Mazingi D, McLean K, Modolo M, Moore R, Morton D, Ntirenganya F, Pata F, Picciochi M, Pockney P, Ramos-De la Medina A, Roberts K, Roslani AC, Kottayasamy Seenivasagam R, Shaw R, Simões JFF, Smart N, Stewart GD, Sullivan R, Sundar S, Tabiri S, Taylor EH, Vidya R, Nepogodiev D, Bhangu A, Glasbey JC, McLean K, Nepogodiev D, Harrison E, Bhangu AA, Nepogodiev D, Siaw-Acheampong K, Benson RA, Bywater E, Chaudhry D, Dawson BE, Evans JP, Glasbey JC, Gujjuri RR, Heritage E, Jones CS, Kamarajah SK, Khatri C, Khaw RA, Keatley JM, Knight A, Lawday S, Li E, Mann HS, Marson EJ, McLean KA, Mckay SC, Mills EC, Pellino G, Picciochi M, Taylor EH, Tiwari A, Simoes JFF, Trout IM, Venn ML, Wilkin RJW, Bhangu A, Glasbey JC, Smart NJ, Minaya-Bravo A, Evans JP, Gallo G, Moug S, Pata F, Pockney P, Di Saverio S, Vallance A, Vimalchandran D, Griffiths EA, Kamarajah SK, Evans RPT, Townend P, Roberts K, McKay S, Isaac J, Satoi S, Edwards J, Coonar AS, Marchbank A, Caruana EJ, Layton GR, Patel A, Brunelli A, Ford S, Desai A, Gronchi A, Fiore M, Almond M, Tirotta F, Dumitra S, Kolias A, Price SJ, Fountain DM, Jenkinson MD, Hutchinson P, Marcus HJ, Piper RJ, Lippa L, Servadei F, Esene I, Freyschlag C, Neville I, Rosseau G, Schaller K, Demetriades AK, Robertson F, Alamri A, Shaw R, Schache AG, Winter SC, Ho M, Nankivell P, Rey Biel J, Batstone M, Ganly I, Vidya R, Wilkins A, Singh JK, Thekinkattil D, Sundar S, Fotopoulou C, Leung EYL, Khan T, Chiva L, Sehouli J, Fagotti A, Cohen P, Gutelkin M, Ghebre R, Konney T, Pareja R, Bristow R, Dowdy S, Shylasree TS, Kottayasamy Seenivasagam R, Ng J, Fujiwara K, Stewart GD, Lamb B, Narahari K, McNeill A, Colquhoun A, McGrath JS, Bromage S, Barod R, Kasivisvaet al., 2021, Effect of COVID-19 pandemic lockdowns on planned cancer surgery for 15 tumour types in 61 countries: an international, prospective, cohort study, The Lancet Oncology, ISSN: 1470-2045

BackgroundSurgery is the main modality of cure for solid cancers and was prioritised to continue during COVID-19 outbreaks. This study aimed to identify immediate areas for system strengthening by comparing the delivery of elective cancer surgery during the COVID-19 pandemic in periods of lockdown versus light restriction.MethodsThis international, prospective, cohort study enrolled 20 006 adult (≥18 years) patients from 466 hospitals in 61 countries with 15 cancer types, who had a decision for curative surgery during the COVID-19 pandemic and were followed up until the point of surgery or cessation of follow-up (Aug 31, 2020). Average national Oxford COVID-19 Stringency Index scores were calculated to define the government response to COVID-19 for each patient for the period they awaited surgery, and classified into light restrictions (index <20), moderate lockdowns (20–60), and full lockdowns (>60). The primary outcome was the non-operation rate (defined as the proportion of patients who did not undergo planned surgery). Cox proportional-hazards regression models were used to explore the associations between lockdowns and non-operation. Intervals from diagnosis to surgery were compared across COVID-19 government response index groups. This study was registered at ClinicalTrials.gov, NCT04384926.FindingsOf eligible patients awaiting surgery, 2003 (10·0%) of 20 006 did not receive surgery after a median follow-up of 23 weeks (IQR 16–30), all of whom had a COVID-19-related reason given for non-operation. Light restrictions were associated with a 0·6% non-operation rate (26 of 4521), moderate lockdowns with a 5·5% rate (201 of 3646; adjusted hazard ratio [HR] 0·81, 95% CI 0·77–0·84; p<0·0001), and full lockdowns with a 15·0% rate (1775 of 11 827; HR 0·51, 0·50–0·53; p<0·0001). In sensitivity analyses, including adjustment for SARS-CoV-2 case notif

Journal article

Peng L, Li J, Wu J, Xu B, Wang Z, Giamas G, Stebbing J, Yu Zet al., 2021, A Pan-Cancer Analysis of SMARCA4 Alterations in Human Cancers, FRONTIERS IN IMMUNOLOGY, Vol: 12, ISSN: 1664-3224

Journal article

Peng L, Yang H, Zhao Y, He J, Stebbing J, Chen Bet al., 2021, Neurolymphomatosis of multifocal peripheral nerve involvement: a case report, Annals of Palliative Medicine, Pages: 1-9, ISSN: 2224-5820

The infiltration and invasion of nerve trunks, nerve roots, and cranial nerves by lymphomatousmalignant cells is defined as “neurolymphomatosis”. It is mainly caused by lymphoma cells directlyinfiltrating the peripheral nerves, with a low incidence. Neurolymphomatosis is a rare condition of neoplasticendoneurial invasion, which is primary or secondary to non-Hodgkin’s lymphoma and leukemia. We describea case of primary peripheral neurolymphomatosis of multifocal involvement in a 77-year-old male patient.He presented with left lower limb pain and was diagnosed with CD20+ diffuse large B cell lymphoma(DLBCL). Magnetic resonance imaging (MRI), fluorine-18 fluorodeoxyglucose (18F-FDG) positron emissiontomography (PET) computed tomography (CT), and nerve biopsy contributed to the diagnosis. Genomicprofiling, programmed death ligand-1 (PD-L1) expression and tumor mutational burden (TMB) were alsoassessed. CDKN2A/CDKN2B deletions have been identified. PD-L1 expression assessed by 28-8 antibodywas 1% positivity, and TMB of the sample was 11.6 muts/Mb. The patient responded well to rituximabcombined with chemotherapy, however, he died after 3 cycles of chemotherapy due to severe lung infectionand subsequent complication of respiratory failure. Here we report the clinical, radiological, pathological andmolecular findings of the patient affected by multifocal neurolymphomatosis without systemic involvementof other organs.

Journal article

Wendler F, Purice T-M, Simon T, Stebbing J, Giamas Get al., 2021, The LMTK-family of kinases: Emerging important players in cell physiology and pathogenesis, BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, Vol: 1867, ISSN: 0925-4439

Journal article

Lythgoe M, Adriani M, Stebbing J, Clark J, Pickford E, Frampton A, Liu D, Kyrgiou M, Rees E, Fyvie G, Stevenson A, Krell Jet al., 2021, 543P Neoadjuvant MRx0518 treatment is associated with significant gene and metagene signature changes in solid tumours, Annals of Oncology, Vol: 32, Pages: S607-S607, ISSN: 0923-7534

BackgroundMRx0518 is an oral live biotherapeutic with potent immunostimulatory activity and anti-tumorigenic efficacy in murine models of lung (LLC1), kidney (Renca) and breast (EMT6) cancer. Previous reports have demonstrated a favourable safety profile in neoadjuvant and metastatic clinical settings, with emerging evidence of immune modulation. We performed a comprehensive analysis of the gene and metagene signature in cancer patients treated with MRx0518 monotherapy.MethodsTreatment-naïve patients with a histologically confirmed diagnosis of cancer scheduled for surgical resection were recruited from April 2019 to February 2020. Patients received 1 capsule of MRx0518 (1x1010 to 1x1011CFU) twice daily from inclusion until the day preceding surgery. Safety and tolerability (CTCAE v4.03) were the primary endpoints of this study. Comprehensive biomarker analysis was also performed in paired pre-treatment (diagnostic biopsy) and post-treatment (surgical specimen) samples using the NanoString IO 360 panel to explore gene and metagene signatures.Results31 samples were collected across tumour groups including breast (n=13) prostate (n=8), uterine (n=6), melanoma (n=2) and bladder (n=2). Differential expression analysis showed significant (p<0.05) increases in genes and metagenes associated with anti-tumour activity, including antigen presentation (AXL & CXCL12), innate immune processes (CHUK, RELA, PPARG & HRAS), interferon response (IFNGR1 & IFNGR2), Th1 cells and CD8+ cells following MRx0518 therapy, echoing preclinical findings. Novel changes, not previously detected in murine models, involving endothelial, mast cells, inflammatory myeloid and inflammatory chemokines were also observed, suggesting MRx0518 may have additional in vivo anti-tumorigenic effects. These changes were more pronounced in the breast cancer cohort.ConclusionsThis analysis, mirrors previous immunostimulatory activity and anti-tumorigenic efficacy observations seen in pre-clini

Journal article

Peng L, Stebbing J, Liang F, Xia Yet al., 2021, Dual immune checkpoint blockade for non-small cell lung cancer patients with PD-L1 high expression: calling an end?, Translational Lung Cancer Research, Vol: 10, Pages: 3858-3860, ISSN: 2218-6751

Journal article

D'Souza N, Monahan K, Benton SC, Wilde L, Abulafi Met al., 2021, Finding the needle in the haystack: the diagnostic accuracy of the faecal immunochemical test for colorectal cancer in younger symptomatic patients, Colorectal Disease, Vol: 23, Pages: 2539-2549, ISSN: 1462-8910

AimDetection of early onset colorectal cancer is challenging, and remains a rare diagnosis amongst younger people with gastrointestinal symptoms. We investigated whether faecal immunochemical testing (FIT) could identify younger patients at higher risk of colorectal cancer or serious bowel disease including colorectal cancer, inflammatory bowel disease or advanced adenomas.MethodsA subgroup analysis was performed of symptomatic patients under 50 years of age (<50) from the NICE FIT study, a multicentre, prospective diagnostic accuracy study of FIT conducted between October 2017 and December 2019. The diagnostic accuracy of FIT for colorectal cancer and serious bowel disease was investigated in younger patients at different faecal haemoglobin (f-Hb) cut-offs of 2, 10 and 150 µg blood/g faeces (µg/g).ResultsEarly onset colorectal cancer was diagnosed in 1.5% (16/1103) of younger symptomatic patients. The sensitivity of FIT for younger patients aged <50 was 87.5% (95% CI 61.7%–98.4%), 81.3% (54.4%–96.0%) and 68.8% (41.3%–89.0%) at f-Hb cut-offs of 2, 10 and 150 µg/g, respectively. The positive predictive value for colorectal cancer increased from 4.2% (2.3%–6.9%) to 11.5% (5.9%–19.6%) at cut-offs of 2 and 150 µg/g, while the positive predictive value for serious bowel disease increased from 31.3% (26.3%–36.5%) to 65.6% (55.2%–75.0%) at the same cut-offs. The negative predictive value of FIT for colorectal cancer remained above 99.5% at all cut-offs.ConclusionDetectable f-Hb on FIT in symptomatic younger patients may indicate referral for investigation of colorectal cancer and serious bowel disease.

Journal article

Melikhov O, Kruglova T, Lytkina K, Melkonyan G, Prokhorovich E, Putsman G, Rodoman G, Vertkin A, Zagrebneva A, Stebbing Jet 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

Journal article

Zhu L, Wang Z, Stebbing J, Wang Z, Peng Let 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.

Journal article

Stebbing J, Lauschke VM, 2021, JAK inhibitors — More than just glucocorticoids, New England Journal of Medicine, Vol: 385, Pages: 463-465, ISSN: 0028-4793

Journal article

Abizanda P, Calbo Mayo JM, Mas Romero M, Cortes Zamora EB, Tabernero Sahuquillo MT, Romero Rizos L, Sanchez-Jurado PM, Sanchez-Nievas G, Campayo Escolano C, Ochoa Serrano A, Sanchez-Flor Alfaro V, Lopez Bru R, Gomez Ballesteros C, Caldevilla Bernardo D, Callejas Gonzalez FJ, Andres-Pretel F, Lauschke VM, Stebbing Jet al., 2021, Baricitinib reduces 30-day mortality in older adults with moderate-to-severe COVID-19 pneumonia, JOURNAL OF THE AMERICAN GERIATRICS SOCIETY, Vol: 69, Pages: 2752-2758, ISSN: 0002-8614

Journal article

Malczewska A, Frampton AE, Mato Prado M, Ameri S, Dabrowska AF, Zagorac S, Clift AK, Kos-Kudła B, Faiz O, Stebbing J, Castellano L, Frilling Aet 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.

Journal article

Peng L, Liang W-H, Mu D-G, Xu S, Hong S-D, Stebbing J, Liang F, Xia Yet 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.

Journal article

Stebbing J, Baranau Y, Baryash V, Manikhas A, Moiseyenko V, Dzagnidze G, Zhavrid E, Boliukh D, Pikiel J, Eniu AE, Li RK, Tiangco B, Lee SJ, Kim Set 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)

Journal article

Jin R, Peng L, Shou J, Wang J, Jin Y, Liang F, Zhao J, Wu M, Li Q, Zhang B, Wu X, Lan F, Xia L, Yan J, Shao Y, Stebbing J, Shen H, Li W, Xia Yet 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.

Journal article

Nteliopoulos G, Page K, Hills A, Howarth K, Emmett W, Green E, Martinson LJ, Fernadez-Garcia D, Hastings R, Guttery DS, Kenny L, Stebbing J, Cleator S, Rehman F, Gleason KLT, Sanela A, Ion C, Rushton AJ, Rosenfeld N, Coombes RC, Shaw JAet 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.

Journal article

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.

Journal article

Stebbing J, Zhang H, Xu Y, Lit LC, Green AR, Grothey A, Lombardo Y, Periyasamy M, Blighe K, Zhang W, Shaw JA, Ellis IO, Lenz HJ, Giamas Get al., 2021, KSR1 regulates BRCA1 degradation and inhibits breast cancer growth (vol 34, pg 2103, 2015), ONCOGENE, ISSN: 0950-9232

Journal article

Balachandran K, Williams J, Bell D, Brown A, Mahmoud S, Hurhangee P, Ramakrishnan R, Cleator S, Coombes RC, Hatcher O, Rehman F, Stebbing J, Kenny Let al., 2021, Breast cancer treatment during the first wave of the COVID-19 pandemic at a UK centre, Publisher: ELSEVIER, Pages: S94-S94, ISSN: 0923-7534

Conference paper

Page K, Martinson LJ, Hastings RK, Fernandez-Garcia D, Gleason KLT, Gray MC, Rushton AJ, Goddard K, Guttery DS, Stebbing J, Coombes RC, Shaw JAet 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

Journal article

Stebbing J, Zhang H, Xu Y, Lit LC, Green AR, Grothey A, Lombardo Y, Periyasamy M, Blighe K, Zhang W, Shaw JA, Ellis IO, Lenz HJ, Giamas Get 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

Journal article

Cilibrasi C, Ditsiou A, Papakyriakou A, Mavridis G, Eravci M, Stebbing J, Gagliano T, Giamas Get al., 2021, LMTK3 inhibition affects microtubule Stability (vol 20, 53, 2021), MOLECULAR CANCER, Vol: 20

Journal article

Salmeron Rios S, Mas Romero M, Cortes Zamora EB, Tabernero Sahuquillo MT, Romero Rizos L, Sanchez-Jurado PM, Sanchez-Nievas G, Senalada JJB, Garcia Nogueras I, Estrella Cazalla JDD, Andres-Pretel F, Murillo Romero A, Lauschke VM, Stebbing J, Abizanda Pet 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

Journal article

Magbanua MJM, Hendrix LH, Hyslop T, Barry WT, Winer EP, Hudis C, Toppmeyer D, Carey LA, Partridge AH, Pierga J-Y, Fehm T, Vidal-Martinez J, Mavroudis D, Garcia-Saenz JA, Stebbing J, Gazzaniga P, Manso L, Zamarchi R, Luisa Antelo M, De Mattos-Arruda L, Generali D, Caldas C, Munzone E, Dirix L, Delson AL, Burstein HJ, Qadir M, Ma C, Scott JH, Bidard F-C, Park JW, Rugo HSet 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

Journal article

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