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European Journal of Cancer
Journal Prestige (SJR): 2.963
Citation Impact (citeScore): 6
Number of Followers: 32  
 
  Hybrid Journal Hybrid journal (It can contain Open Access articles)
ISSN (Print) 0959-8049
Published by Elsevier Homepage  [3168 journals]
  • Clinical progression is associated with poor prognosis whatever the
           treatment line in metastatic castration resistant prostate cancer: The
           CATS international database
    • Abstract: Publication date: Available online 29 November 2019Source: European Journal of CancerAuthor(s): Nicolas Delanoy, Anne-Claire Hardy-Bessard, Eleni Efstathiou, Sylvestre Le Moulec, Umberto Basso, Alison Birtle, Alastair Thomson, Michael Krainer, Aline Guillot, Ugo De Giorgi, Ali Hasbini, Gedske Daugaard, Amit Bahl, Simon Chowdhury, Orazio Caffo, Philippe Beuzeboc, Dominique Spaeth, Jean-Christophe Eymard, Aude Fléchon, Jerome AlexandreAbstractAim of the studyOur goal was to evaluate the impact of progression type (prostate-specific antigen [PSA] only, radiological or clinical) at initiation of first-, second- and third life-extending therapy (LET) on treatment outcomes in metastatic castration-resistant prostate cancer (mCRPC) patients, by performing a post-hoc analysis using data from the CATS international registry.MethodsThe 669 consecutive mCRPC patients of the CATS registry were classified according to their type of progression at initiation of each LET: PSA only (PSA-p), radiological (±PSA) (Radio-p); or clinical (±PSA, ±radiological) progression (Clin-p). Overall survival (OS), the primary endpoint, was calculated from initiation of the first-, second- and third-LET to death for each sequence.ResultsMedian OS was shorter in the Clin-p group compared with the PSA-p group (14-month difference in first line; around 7-month difference in second- and third line). Shorter progression-free survival (PFS) was also observed in Clin-p patients, whatever the treatment is. Clinical progression seemed to be associated with a shorter duration of therapy with androgen receptor-targeted therapy (ART) compared with taxanes.ConclusionsClinical progression at initiation of a LET is associated with poor outcomes including shorter PFS and OS as well as clinical and biological features of aggressive disease. Stratifying patients in clinical trials according to disease progression type may prevent selection bias and data heterogeneity. In daily practice, first signs of clinical progression may prompt physicians to consider starting a new LET, independently of PSA levels.
       
  • New evidence confirms that reproductive risk factors can be used to
           stratify breast cancer risks: Implications for a new population screening
           paradigm
    • Abstract: Publication date: Available online 26 November 2019Source: European Journal of CancerAuthor(s): D. Gareth Evans, Sacha J. Howell, Anthony Howell
       
  • Causes of cancer: Perceptions vs. the scientific evidence
    • Abstract: Publication date: Available online 19 November 2019Source: European Journal of CancerAuthor(s): Priyanka Bandara, David O. Carpenter
       
  • Response to letter: Causes of cancer: Perceptions versus the scientific
           evidence by Bandara and Carpenter
    • Abstract: Publication date: Available online 9 November 2019Source: European Journal of CancerAuthor(s): Lion Shahab, Samuel G. Smith
       
  • Health-related quality of life in patients with fully resected BRAF V600
           mutation–positive melanoma receiving adjuvant vemurafenib
    • Abstract: Publication date: December 2019Source: European Journal of Cancer, Volume 123Author(s): Dirk Schadendorf, Anna Maria Di Giacomo, Lev Demidov, Barbara Merelli, Igor Bondarenko, Paolo A. Ascierto, Christopher Herbert, Andrzej Mackiewicz, Piotr Rutkowski, Alexander Guminski, Grant R. Goodman, Brian Simmons, Chenglin Ye, Agnes Hong, Karl Lewis, the BRIM8 InvestigatorsAbstractAim of studyThe aim of the study was to assess the impact of treatment with adjuvant vemurafenib monotherapy on health-related quality of life (HRQOL) in patients with resected stage IIC–IIIC melanoma.MethodsThe phase 3 BRIM8 study (NCT01667419) randomised patients with BRAFV600 mutation–positive resected stage IIC–IIIC melanoma to 960 mg of vemurafenib twice daily or matching placebo for 52 weeks (13 × 28-day cycles). Patients completed the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) version 3 at baseline, cycle 1 (days 1, 15 and 22), cycle 2 (days 1 and 15), day 1 of every subsequent 4-week cycle, the end-of-treatment visit and each visit during the follow-up period.ResultsCompletion rates for the EORTC QLQ-C30 questionnaire were high (>80%). There was a mean decline in the global health status (GHS)/quality of life (QOL) score of 17.4 (±22.9) and 17.3 (±24.1) points at days 15 and 22 of cycle 1, respectively, among vemurafenib-treated patients who recovered to approximately 10 points below baseline for the remainder of the treatment period. A similar trend was observed in all functional scales except for cognitive function (
       
  • Corrigendum to ‘Prediction of melanoma evolution in melanocytic nevi via
           artificial intelligence: A call for prospective data’ [Eur J Cancer, 119
           (September 2019) Pages 30–34]
    • Abstract: Publication date: Available online 7 November 2019Source: European Journal of CancerAuthor(s): Wiebke Sondermann, Jochen Sven Utikal, Alexander H. Enk, Dirk Schadendorf, Joachim Klode, Axel Hauschild, Michael Weichenthal, Lars E. French, Carola Berking, Bastian Schilling, Sebastian Haferkamp, Stefan Fröhling, Christof von Kalle, Titus J. Brinker
       
  • Valuing preferences for treating screen detected ductal carcinoma in
           situ
    • Abstract: Publication date: December 2019Source: European Journal of Cancer, Volume 123Author(s): Hannah L. Bromley, G. Bruce Mann, Dennis Petrie, Carolyn Nickson, Daniel Rea, Tracy E. RobertsAbstractBackgroundMammographic screening reduces breast cancer mortality but may lead to the overdiagnosis and overtreatment of low-risk breast cancers. Conservative management may reduce the potential harm of overtreatment, yet little is known about the impact upon quality of life.ObjectivesTo quantify women's preferences for managing low-risk screen detected ductal carcinoma in situ (DCIS), including the acceptability of active monitoring as an alternative treatment.MethodsUtilities (cardinal measures of quality of life) were elicited from 172 women using visual analogue scales (VASs), standard gambles, and the Euro-Qol-5D-5L questionnaire for seven health states describing treatments for low-risk DCIS. Sociodemographics and breast cancer history were examined as predictors of utility.ResultsBoth patients and non-patients valued active monitoring more favourably on average than conventional treatment. Utilities were lowest for DCIS treated with mastectomy (VAS: 0.454) or breast conserving surgery (BCS) with adjuvant radiotherapy (VAS: 0.575). The utility of active monitoring was comparable to BCS alone but was rated more favourably as progression risk was reduced from 40% to 10%. Disutility for active monitoring was likely driven by anxiety around progression, whereas conventional management impacted other dimensions of quality of life. The heterogeneity between individual preferences could not be explained by sociodemographic variables, suggesting that the factors influencing women's preferences are complex.ConclusionsActive monitoring of low-risk DCIS is likely to be an acceptable alternative for reducing the impact of overdiagnosis and overtreatment in terms of quality of life. Further research is required to determine subgroups more likely to opt for conservative management.
       
  • Phase II study of CC-486 (oral azacitidine) in previously treated patients
           with locally advanced or metastatic nasopharyngeal carcinoma
    • Abstract: Publication date: December 2019Source: European Journal of Cancer, Volume 123Author(s): Ricard Mesia, Paolo Bossi, Aaron R. Hansen, Ching-Yun Hsieh, Lisa F. Licitra, Eng-Huat Tan, Peng Chen, JulieAnn Miller, Lilian L. Siu, Robert I. HaddadAbstractBackgroundTreatment options are limited for recurrent nasopharyngeal carcinoma (NPC). We report results from a phase II study of CC-486 (oral azacitidine) in advanced NPC.Patients and methodsPatients with locally advanced or metastatic NPC and 1–2 prior treatment regimens received CC-486 300 mg daily on days 1–14 of 21-day cycles until disease progression or unacceptable toxicity. The first 6 patients of Asian-Pacific Islander (API) ethnicity received a reduced dose of 200 mg to preserve safety and tolerability; if well tolerated, subsequent API patients received CC-486 300 mg. The study could advance to stage 2 if > 4 patients achieved a response. Co-primary end-points were overall response rate (ORR) and progression-free survival (independent review). Key secondary end-points were overall survival and safety.ResultsOwing to faster-than-anticipated enrolment, 36 patients, including 13 of API ethnicity, were enrolled; the median age was 54.0 years. Most patients were male (81%) and had an Eastern Cooperative Oncology Group performance status ≤ 1 (97%). Among 25 efficacy-evaluable patients, the ORR was 12%; the median progression-free and overall survival were 4.7 and 18.0 months, respectively. The most common grade III/IV treatment-emergent adverse events were neutropenia (33%) and febrile neutropenia (11%). Twenty-one posttreatment deaths, primarily due to progressive disease or disease complications, and 1 on-treatment death (epistaxis, unrelated to study drug) occurred. The study did not advance to stage 2.ConclusionCC-486 did not show sufficient clinical activity to support further development as monotherapy in this patient population. The safety profile of CC-486 in NPC was consistent with that in other solid tumours.
       
  • Safety and effectiveness of regorafenib in patients with metastatic
           colorectal cancer in routine clinical practice in the prospective,
           observational CORRELATE study
    • Abstract: Publication date: December 2019Source: European Journal of Cancer, Volume 123Author(s): Michel Ducreux, Lone Nørgård Petersen, Leopold Öhler, Francesca Bergamo, Jean-Philippe Metges, Jan Willem de Groot, Jaw-Yuan Wang, Beatriz García Paredes, Emmanuelle Dochy, Sabine Fiala-Buskies, Andrés Cervantes, Juan Manuel O'Connor, Alfredo Falcone, CORRELATE InvestigatorsAbstractBackgroundRegorafenib prolonged overall survival (OS) versus placebo in patients with treatment-refractory metastatic colorectal cancer (mCRC) in phase III trials. We conducted an observational study of regorafenib for patients with mCRC in real-world clinical practice.MethodsThe international, prospective, CORRELATE study recruited patients with mCRC previously treated with approved therapies, for whom the decision to treat with regorafenib was made by the treating physician according to the local health authority approved label. The primary objective was safety, assessed by treatment-emergent adverse events (TEAEs; National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03).ResultsA total of 1037 patients were treated. The median age was 65 years (range: 24–93); 87% of patients had Eastern Cooperative Oncology Group performance status 0–1, 56% of patients had KRAS, 7% had NRAS and 4% had BRAF mutations. The initial regorafenib dose was 160 mg/day in 57% of patients. The most common grade III or IV drug-related TEAEs were fatigue (9%), hand–foot skin reaction (7%) and hypertension (6%). Drug-related grade V (fatal) TEAEs occurred in 1% of patients. Dose reductions for drug-related TEAEs occurred in 24% of patients. Median OS was 7.7 months (95% confidence interval [CI]: 7.2–8.3), and median progression-free survival (PFS) was 2.9 months (95% CI: 2.8–3.0).ConclusionsIn this real-world, observational study of patients with mCRC, the regorafenib toxicity profile was similar to that reported in phase III trials. The starting dose for almost half of patients was less than the approved 160-mg dose, and the median OS and PFS were in the range observed in phase III trials.Trial registration: NCT02042144.
       
  • The correlation between immune subtypes and consensus molecular subtypes
           in colorectal cancer identifies novel tumour microenvironment profiles,
           with prognostic and therapeutic implications
    • Abstract: Publication date: December 2019Source: European Journal of Cancer, Volume 123Author(s): B. Soldevilla, C. Carretero-Puche, G. Gomez-Lopez, F. Al-Shahrour, M.C. Riesco, B. Gil-Calderon, L. Alvarez-Vallina, P. Espinosa-Olarte, G. Gomez-Esteves, B. Rubio-Cuesta, J. Sarmentero, A. La Salvia, R. Garcia-CarboneroAbstractBackgroundSolid tumour growth is the consequence of a complex interplay between cancer cells and their microenvironment. Recently, a new global transcriptomic immune classification of solid tumours has identified six immune subtypes (ISs) (C1–C6). Our aim was to specifically characterise ISs in colorectal cancer (CRC) and assess their interplay with the consensus molecular subtypes (CMSs).MethodsClinical and molecular information, including CMSs and ISs, were obtained from The Cancer Genome Atlas (TCGA) (N = 625). Immune cell populations, differential gene expression and gene set enrichment analysis were performed to characterise ISs in the global CRC population by using CMSs.ResultsOnly 5 ISs were identified in CRC, predominantly C1 wound healing (77%) and C2 IFN-γ dominant (17%). CMS1 showed the highest proportion of C2 (53%), whereas C1 was particularly dominant in CMS2 (91%). CMS3 had the highest representation of C3 inflammatory (7%) and C4 lymphocyte depleted ISs (4%), whereas all C6 TGF-β dominant cases belonged to CMS4 (2.3%). Prognostic relevance of ISs in CRC substantially differed from that reported for the global TCGA, and ISs had a greater ability to stratify the prognosis of CRC patients than CMS classification. C2 had higher densities of CD8, CD4 activated, follicular helper T cells, regulatory T cells and neutrophils and the highest M1/M2 polarisation. C2 had a heightened activation of pathways related to the immune system, apoptosis and DNA repair, mTOR signalling and oxidative phosphorylation, whereas C1 was more dependent of metabolic pathways.ConclusionsThe correlation of IS and CMS allows a more precise categorisation of patients with relevant clinical and biological implications, which may be valuable tools to improve tailored therapeutic interventions in CRC patients.
       
  • Increased reporting of fatal hepatitis associated with immune checkpoint
           inhibitors
    • Abstract: Publication date: December 2019Source: European Journal of Cancer, Volume 123Author(s): Aurore Vozy, Eleonora De Martin, Douglas B. Johnson, Bénédicte Lebrun-Vignes, Javid J. Moslehi, Joe-Elie Salem
       
  • Melanoma-specific survival in patients with positive sentinel lymph nodes:
           Relevance of sentinel tumor burden
    • Abstract: Publication date: December 2019Source: European Journal of Cancer, Volume 123Author(s): Imke Satzger, Ulrike Leiter, Nikolai Gräger, Ulrike Keim, Claus Garbe, Ralf GutzmerAbstractBackgroundThe tumor burden within the sentinel lymph node (SLN) is not included in the 8th edition of the American Joint Committee of Cancer (AJCC) melanoma classification. Therefore, we analysed the prognostic relevance of the SLN tumor burden in the stage III subgroups.Patients and methodsA total of 736 patients with melanoma with positive SLN and long-term follow-up (mean, 64.4 months; median, 59.0 months) were assessed. SLN tumor burden was evaluated by the maximum diameter of the largest deposit in all patients.ResultsBy univariate Kaplan-Meier analyses, melanoma-specific survival (MSS) of patients in stage IIIA, IIIB and IIIC and lower sentinel tumor burden (cut-offs ≤0.5 mm and ≤1 mm) was significantly better than that in patients with higher sentinel tumor load (>0.5 mm and>1 mm).By multivariate analysis using the Cox model, the maximum diameter of the largest deposit (cut-off ≤0.5 mm versus>0.5 mm and cut-off ≤1 mm as continuous variables) represented an independent prognostic parameter for MSS in stage III patients. Cut-off of 0.5 mm showed a slightly higher area under the receiver operating characteristic curve (AUC = 0.617) when than the cut-off of 1 mm (AUC = 0.599).ConclusionThe prognosis of patients with stage III melanoma can be determined more precisely if the SLN tumor burden is considered, also within the existing AJCC subgroups. Thus, this parameter should be included in future classifications, and our study provides benchmarks in estimating prognosis and counselling patients with melanoma with positive sentinel nodes beyond the 8th AJCC Cancer Staging Manual. The optimal cut-off remains for SLN tumor burden remains to be determined, but our results suggest that a cut-off lower than 1 mm is preferable.
       
  • Disease-free survival as a surrogate for overall survival in neoadjuvant
           trials of gastroesophageal adenocarcinoma: Pooled analysis of individual
           patient data from randomised controlled trials
    • Abstract: Publication date: December 2019Source: European Journal of Cancer, Volume 123Author(s): Ulrich Ronellenfitsch, Katrin Jensen, Svenja Seide, Meinhard Kieser, Matthias Schwarzbach, Tracy E. Slanger, Bryan Burmeister, David Kelsen, Donna Niedzwiecki, Guillaume Piessen, Christoph Schuhmacher, Susan Urba, Cornelis van de Velde, Marc Ychou, Ralf Hofheinz, Sylvie LorenzenAbstractIntroductionDisease-free survival (DFS) is increasingly being used as surrogate end-point for overall survival (OS) in cancer trials. So far, there has been no validation of the surrogacy of DFS for OS for neoadjuvant treatment of gastroesophageal adenocarcinoma.MethodsThe study uses individual patient data (IPD) from eight randomised controlled trials (RCTs) (n = 1126 patients) comparing neoadjuvant therapy followed by surgery with surgery alone for gastroesophageal adenocarcinoma. Correlation between OS time and DFS time was calculated to evaluate individual-level surrogacy. For each trial, survival curves using the Kaplan-Meier method were plotted and hazard ratios (HRs) on the treatment effects were calculated for OS and DFS separately. Those HRs were pooled in a random-effects meta-analysis. Observed HRs were compared with predicted HRs for OS using results from an error-in-variables linear regression model accounting for the uncertainty about the estimated effect. The strength of the association was quantified by the coefficient of determination to assess trial-level surrogacy. The surrogate threshold effect was calculated to determine the minimum treatment effect on DFS necessary to predict a non-zero treatment effect on OS.ResultsA strong correlation between OS time and DFS time was observed, indicating a high individual-level surrogacy. For all RCTs, estimated HRs for OS and DFS were highly similar. In the meta-analysis, the overall HR for OS was virtually identical to that for DFS. The estimated coefficient of determination r2 for the association between HRs for OS and DFS was 0.912 (95% confidence interval: 0.75–1.0), indicating a very good fit of the regression model and thus a strong trial-level surrogacy between OS and DFS. The surrogate threshold effect based on the regression analysis was 0.79.DiscussionBased on strong correlations between DFS and OS, as well as a strong correlation of the treatment effects of the two end-points in the error-in-variable regression, DFS seems an appropriate surrogate marker for OS in randomised trials of neoadjuvant chemotherapy or chemoradiotherapy for gastroesophageal adenocarcinoma.
       
  • Everolimus after hepatic arterial embolisation therapy of metastases from
           gastrointestinal neuroendocrine tumours: The FFCD 1104-EVACEL-GTE phase II
           study
    • Abstract: Publication date: December 2019Source: European Journal of Cancer, Volume 123Author(s): Thomas Walter, Come Lepage, Romain Coriat, Emilie Barbier, Guillaume Cadiot, Francois-Xavier Caroli-Bosc, Thomas Aparicio, Karine Bouhier-Leporrier, Olivia Hentic-Dhome, Frédérique Gay, Anne-Claire Dupont-Gossart, Muriel Duluc, Céline Lepere, Thierry Lecomte, Denis Smith, Caroline Petorin, Frédéric Di-Fiore, Francois Ghiringhelli, Jean-Louis Legoux, Rosine GuimbaudAbstractBackgroundHepatic arterial embolisation therapy (HAET) is a treatment of liver metastases of gastrointestinal neuroendocrine tumours (GI-NETs). HAET increases circulating vascular endothelial growth factor levels. Everolimus is a treatment in NETs that may have antiangiogenic activity.MethodsThis phase II study was conducted in patients with predominant and progressive liver metastases from GI-NETs. Everolimus was initiated 7–30 days after HAET. The hypothesis was that everolimus after HAET would increase hepatic progression-free survival (hPFS) rate at 24 months from 35% to 50%.ResultsAmong the 74 patients included, 88% had small-bowel primary tumour, 43% had grade I and 57% grade II tumour, and 51% had extrahepatic metastases. Patients underwent one (n = 19), two (n = 54), or three (n = 1) HAET procedures. hPFS at 24 months was 33% (95% confidence interval [CI], 22.5–43.7); 40 (54%) patients had objective response. Median (95% CI) hPFS, PFS, and overall survival were 19 (14–23), 17 (13–22), and 51 (33–60) months. The most common grade III–IV toxicities (>5%) in patients receiving both HAET and everolimus (n = 67) were elevated liver enzymes (55%), fatigue (18%), diarrhoea (16%), anaemia (12%), hypertriglyceridaemia (7%) and mucositis (6%).ConclusionsThe primary end-point was not reached. This sequence allows high liver response with HAET, and everolimus controls the extrahepatic disease.Trial registrationNCT01678664 (clinicaltrials.gov).
       
  • Overestimated treatment effects in randomised phase II trials: What's up
           doctor'
    • Abstract: Publication date: December 2019Source: European Journal of Cancer, Volume 123Author(s): Stefan Michiels, James Wason
       
  • Statins use and prostate cancer mortality
    • Abstract: Publication date: Available online 31 October 2019Source: European Journal of CancerAuthor(s): Shih-Wei Lai, Yu-Hung Kuo, Kuan-Fu Liao
       
  • Negative phase III trials announce the need for biomarkers in sarcoma
    • Abstract: Publication date: December 2019Source: European Journal of Cancer, Volume 123Author(s): Alexander TJ. Lee, Paul H. Huang, Robin L. Jones
       
  • Real-life results from the overall population and key subgroups within the
           Italian cohort of nivolumab expanded access program in non-squamous
           non–small cell lung cancer
    • Abstract: Publication date: December 2019Source: European Journal of Cancer, Volume 123Author(s): Francesco Grossi, Carlo Genova, Lucio Crinò, Angelo Delmonte, Daniele Turci, Diego Signorelli, Antonio Passaro, Hector Soto Parra, Annamaria Catino, Lorenza Landi, Francesco Gelsomino, Marcello Tiseo, Gianfranco Puppo, Fausto Roila, Serena Ricciardi, Giuseppe Tonini, Francesco Cognetti, Luca Toschi, Davide Tassinari, Alessandro ScoppolaAbstractBackgroundNivolumab was the first immune checkpoint inhibitor approved for previously treated advanced non–small cell lung cancer (NSCLC). Before its introduction in the market, nivolumab was made available to NSCLC patients through an expanded access program (EAP). Here we present the Italian cohort of patients with non-squamous NSCLC enrolled in a worldwide nivolumab EAP, with subgroup analyses involving elderly patients, patients with central nervous system (CNS) metastases and patients receiving nivolumab beyond progression.MethodsPretreated patients with advanced non-squamous NSCLC received nivolumab at 3 mg/kg every 2 weeks up to 24 months. Efficacy data (investigator-assessed tumour response, progression date and survival) and safety data were collected.Findings1588 patients were treated across 153 Italian centres. Overall response rate and disease control rate were 18% and 44%, respectively; median overall survival (OS) was 11.3 months (95% CI: 10.2–12.4). Elderly patients (≥70 n = 522; ≥75 n = 232) achieved outcomes similar to the global study population; patients with CNS metastases (n = 409) had an OS of 8.6 months (95% CI: 6.4–10.8), and a 1-year OS rate of 43%. Nivolumab was administered beyond progression to 276 patients (26%), 57 of whom achieved subsequent disease control; the median OS of patients receiving nivolumab beyond progression was 16.2 months (95% CI: 14.0–18.4), while 1-year OS rate was 62%.InterpretationTo date, this is the largest clinical experience with nivolumab in a real-world setting. Our data support its use in clinical practice for pretreated non-squamous NSCLC, including patients with older age or CNS metastases.
       
  • EORTC Lung Cancer Group survey on the definition of NSCLC synchronous
           oligometastatic disease
    • Abstract: Publication date: November 2019Source: European Journal of Cancer, Volume 122Author(s): Antonin Levy, Lizza E.L. Hendriks, Thierry Berghmans, Corinne Faivre-Finn, Matteo GiajLevra, Niccolò GiajLevra, Baktiar Hasan, Alessia Pochesci, Nicolas Girard, Laurent Greillier, Sylvie Lantuéjoul, John Edwards, Mary O'Brien, Martin Reck, Benjamin Besse, Silvia Novello, Anne-Marie C. Dingemans, EORTC Lung Cancer Group (EORTC LCG)AbstractBackgroundSynchronous oligometastatic disease (sOM) has been described as a distinct disease entity; however, there is no consensus on OM definition (OM-d) in non–small-cell lung cancer (NSCLC). A consensus group was formed aiming to agree on a common OM-d that could be used in future clinical trials. A European survey was circulated to generate questions and input for the consensus group meeting.MethodsA European Organisation for Research and Treatment of Cancer Lung Cancer Group (LCG)/sOM-d consensus group survey was distributed to LCG, sOM-d consensus group, and several European thoracic oncology societies’ members.Results444 responses were analysed (radiation oncologist: 55% [n = 242], pulmonologist: 15% [n = 66], medical oncologist: 14% [n = 64]). 361 physicians (81%) aimed to cure sOM NSCLC patients and 82% (n = 362) included the possibility of radical intent treatment in their sOM-d. The maximum number of metastases considered in sOM-d varied: 12% replied 1 metastasis, 42% ≤ 3, and 17% ≥ 5 metastases. 79% (n = 353) stated that number of organs involved was important for sOM-d, and most (80%, n = 355) considered that only ≤3 involved organs (excluding primary) should be included. 317 (72%) included mediastinal lymph node involvement in the sOM-d and 22% (n = 70/317) counted mediastinal lymph node as a metastatic site. Most physicians completed sOM staging with brain magnetic resonance imaging (91%, n = 403) and positron emission tomography/computed tomography (98%, n = 437). Pathology proof of metastatic disease was a requirement to define sOM for 315 (71%) physicians. The preferred primary outcome for sOM clinical trials was overall survival (73%, n = 325).ConclusionAlthough consensual answers were obtained, several issues remain unresolved and will require further research to agree on a sOM-d.
       
  • A systematic literature review and network meta-analysis of effectiveness
           and safety outcomes in advanced melanoma
    • Abstract: Publication date: December 2019Source: European Journal of Cancer, Volume 123Author(s): Margreet G. Franken, Brenda Leeneman, Maria Gheorghe, Carin A. Uyl-de Groot, John B.A.G. Haanen, Pieter H.M. van BaalAbstractBackgroundAlthough a myriad of novel treatments entered the treatment paradigm for advanced melanoma, there is lack of head-to-head evidence. We conducted a network meta-analysis (NMA) to estimate each treatment's relative effectiveness and safety.MethodsA systematic literature review (SLR) was conducted in Embase, MEDLINE and Cochrane to identify all phase III randomised controlled trials (RCTs) with a time frame from January 1, 2010 to March 11, 2019. We retrieved evidence on treatment-related grade III/IV adverse events, progression-free survival (PFS) and overall survival (OS). Evidence was synthesised using a Bayesian fixed-effect NMA. Reference treatment was dacarbazine. In accordance with RCTs, dacarbazine was pooled with temozolomide, paclitaxel and paclitaxel plus carboplatin. To increase homogeneity of the study populations, RCTs were only included if patients were not previously treated with novel treatments.ResultsThe SLR identified 28 phase III RCTs involving 14,376 patients. Nineteen and seventeen treatments were included in the effectiveness and safety NMA, respectively. For PFS, dabrafenib plus trametinib (hazard ratio [HR] PFS: 0.21) and vemurafenib plus cobimetinib (HR PFS: 0.22) were identified as most favourable treatments. Both had, however, less favourable safety profiles. Five other treatments closely followed (dabrafenib [HR PFS: 0.30], nivolumab plus ipilimumab [HR PFS: 0.34], vemurafenib [HR PFS: 0.38], nivolumab [HR PFS: 0.42] and pembrolizumab [HR PFS: 0.46]). In contrast, for OS, nivolumab plus ipilimumab (HR OS: 0.39), nivolumab (HR OS: 0.46) and pembrolizumab (HR OS: 0.50) were more favourable than dabrafenib plus trametinib (HR OS: 0.55) and vemurafenib plus cobimetinib (HR OS: 0.57).ConclusionsOur NMA identified the most effective treatment options for advanced melanoma and provided valuable insights into each novel treatment's relative effectiveness and safety. This information may facilitate evidence-based decision-making and may support the optimisation of treatment and outcomes in everyday clinical practice.
       
  • Dietary 2-deoxy-D-glucose impairs tumour growth and metastasis by
           inhibiting angiogenesis
    • Abstract: Publication date: December 2019Source: European Journal of Cancer, Volume 123Author(s): Saurabh Singh, Sanjay Pandey, Amanpreet Singh Chawla, Anant Narayan Bhatt, Bal Gangadhar Roy, Daman Saluja, Bilikere S. DwarakanathAbstractAccumulating evidence suggests the antiangiogenic potential of the glycolytic inhibitor 2-deoxy-D-glucose (2-DG) among the anticancerous properties of this drug. In the present studies, we investigated the antiangiogenic effects of dietary 2-DG on tumour (Lewis lung carcinoma [LLC]) as well as ionising radiation–induced angiogenesis in mouse models. Dietary 2-DG reduced the serum vascular endothelial growth factor levels (∼40%) in LLC-bearing mice along with a significant inhibition of tumour growth and metastases. In vivo Matrigel plug assays showed significant decrease in vascularisation, Fluorescein isothiocyanate (FITC)-dextran fluorescence and factor VIII–positive cells in the plugs from 2-DG–fed mice, supporting the notion that dietary 2-DG significantly suppresses the tumour-associated and radiation-induced angiogenesis. 2-DG inhibited the glucose usage and lactate production as well as ATP levels of human umbilical vein endothelial cells (HUVECs) in a concentration-dependent manner, accompanied by growth inhibition and loss of viability in vitro. Furthermore, 2-DG inhibited the capillary-like tube formation in Matrigel as well as migration and transwell invasion by HUVECs, which are functional indicators of the process of angiogenesis. These results suggest that dietary 2-DG inhibits processes related to angiogenesis, which can impair the growth and metastasis of tumours.
       
  • Revocation of the conditional marketing authorisation of a cancer
           medicine: The olaratumab experience
    • Abstract: Publication date: December 2019Source: European Journal of Cancer, Volume 123Author(s): Ralf Herold, Jorge Camarero, Daniela Melchiorri, Zigmars Sebris, Harald Enzmann, Francesco Pignatti
       
  • DNA epigenetic signature predictive of benefit from neoadjuvant
           chemotherapy in oesophageal adenocarcinoma: results from the MRC OE02
           trial
    • Abstract: Publication date: December 2019Source: European Journal of Cancer, Volume 123Author(s): Raghav Sundar, Alvin Ng, Hermioni Zouridis, Nisha Padmanabhan, Taotao Sheng, Shenli Zhang, Ming Hui Lee, Wen Fong Ooi, Aditi Qamra, Imran Inam, Lindsay C. Hewitt, Jimmy Bok-Yan So, Vivien Koh, Matthew G. Nankivell, Ruth E. Langley, William H. Allum, David Cunningham, Steven G. Rozen, Wei Peng Yong, Heike I. GrabschAbstractBackgroundDNA methylation signatures describing distinct histological subtypes of oesophageal cancer have been reported. We studied DNA methylation in samples from the MRC OE02 phase III trial, which randomised patients with resectable oesophageal cancer to surgery alone (S) or neoadjuvant chemotherapy followed by surgery (CS).AimThe aim of the study was to identify epigenetic signatures predictive of chemotherapy benefit in patients with oesophageal adenocarcinoma (OAC) from the OE02 trial and validate the findings in an independent cohort.MethodsDNA methylation was analysed using the Illumina GoldenGate platform on surgically resected OAC specimens from patients in the OE02 trial. Cox proportional hazard analysis was performed to select probes predictive of survival in the CS arm. Non-negative matrix factorisation was used to perform clustering and delineate DNA methylation signatures. The findings were validated in an independent cohort of patients with gastroesophageal adenocarcinoma treated with neoadjuvant chemotherapy.ResultsA total of 229 patients with OAC were analysed from the OE02 trial (118 in the CS arm and 111 in the S arm). There was no difference in DNA methylation status between the CS and S arms. A metagene signature was created by dichotomising samples into two clusters. In cluster 1, patients in the CS arm had significant overall survival (OS) benefit (median OS CS: 931 days vs. S: 536 days [HR: 1.54, P = 0.031]). In cluster 2, patients in the CS arm had similar (or worse) OS compared with patients in the S arm (CS: 348 days vs. S: 472 days [HR: 0.70, P = 0.1], and test of interaction was significant (p = 0.005). In the validation cohort (n = 13), there was no difference in DNA methylation status in paired pre- and post-treatment samples. When the epigenetic signature was applied, cluster 1 samples had better OS (median OS, cluster 1: 1174 days vs. cluster 2: 392 days, HR: 3.47, p = 0.059)ConclusionsThis is the first and largest study of DNA methylation in patients with OAC uniformly treated in a randomised phase III trial. We identified an epigenetic signature that may serve as a predictive biomarker for chemotherapy benefit in OAC.
       
  • Patritumab or placebo, with cetuximab plus platinum therapy in recurrent
           or metastatic squamous cell carcinoma of the head and neck: A randomised
           phase II study
    • Abstract: Publication date: December 2019Source: European Journal of Cancer, Volume 123Author(s): Martin D. Forster, Magnus T. Dillon, Judit Kocsis, Éva Remenár, Gabor Pajkos, Frederic Rolland, Jonathan Greenberg, Kevin J. HarringtonAbstractBackgroundThe fully human monoclonal antibody patritumab blocks HER3 activation, a resistance mechanism to cetuximab, induced by heregulin (HRG). A phase Ib study in recurrent and/or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN) demonstrated tolerability and tumour response of patritumab + cetuximab + platinum.MethodsThis was a randomised, double-blind, phase II study of patritumab + cetuximab with platinum-based therapy for first-line treatment of R/M SCCHN (Clinicaltrials.gov identifier: NCT02633800). Patients aged ≥18 years received patritumab or placebo, both combined with cetuximab + cisplatin or carboplatin. Co-primary end-points were progression-free survival (PFS) in the intent-to-treat (ITT) and the high-expression HRG (HRG high) populations.ResultsEighty-seven patients (n = 43 in the patritumab group; n = 44 in placebo group) enrolled. A median (range) of 6.5 (1–24) patritumab cycles were completed. Median PFS was similar between the patritumab group and placebo group in the ITT population (5.6 versus 5.5 months; hazard ratio [HR] 0.99 [95% confidence interval [CI], 0.6–1.7]; P = 0.96) and HRG-high subgroup (n = 51; 5.6 versus 5.6 months; HR 0.93 [95% CI, 0.5–1.8]; P = 0.82). Median overall survival in the ITT population was also similar (10.0 versus 12.7 months; HR 1.3 [95% CI, 0.69–2.29]; P = 0.46). All patients experienced ≥1 treatment-emergent adverse event (TEAE). Grade ≥III TEAEs were more frequent in the patritumab than the placebo group (84.1% versus 60.5%). The most common grade ≥III patritumab-related TEAE in the patritumab group (20.5% overall) was rash (6.8%).ConclusionPatritumab + cetuximab + platinum was tolerable but not superior to cetuximab + platinum.
       
  • Re: Deep learning outperformed 11 pathologists in the classification of
           histopathological melanoma images
    • Abstract: Publication date: Available online 23 October 2019Source: European Journal of CancerAuthor(s): Cyrill Géraud, Klaus G. Griewank
       
  • Vinflunine/gemcitabine versus carboplatin/gemcitabine as first-line
           treatment in cisplatin-ineligible patients with advanced urothelial
           carcinoma: A randomised phase II trial (VINGEM)
    • Abstract: Publication date: Available online 22 October 2019Source: European Journal of CancerAuthor(s): Karin Holmsten, Niels Viggo Jensen, Lene Sonne Mouritsen, Erika Jonsson, Camilla Mellnert, Mads Agerbæk, Cecilia Nilsson, Mette Moe, Andreas Carus, Elisabeth Öfverholm, Outi Lahdenperä, Yvonne Brandberg, Hemming Johansson, Mats Hellström, Hans von der Maase, Helle Pappot, Anders UllénAbstractBackgroundThe present study (VINGEM) is the first randomised trial comparing vinflunine/gemcitabine (VG) to standard carboplatin/gemcitabine (CG) in patients with advanced urothelial carcinoma (aUC) ineligible for treatment with cisplatin.Patients and methodsPatients with aUC, creatinine clearance 30–60 ml/min, performance status ≤1 and no prior chemotherapy for metastatic disease were randomised to the experimental arm (vinflunine 280 or 250 mg/m2 day 1, gemcitabine 1000 mg/m2 days 1 and 8, q21 days) or the control arm (carboplatin AUC 4.5 day 1, gemcitabine 1000 mg/m2 days 1 and 8, q21 days). Primary end-point was progression-free survival (PFS).ResultsSixty-two patients were randomised; a total of 59 patients were treated (29 VG, 30 CG). There was no significant difference in PFS between the treatment arms: median 6.2 months for VG versus 6.3 months for CG (hazard ratio [HR]: 0.75, 95% confidence interval [CI]: 0.44–1.28; P = 0.293). Median overall survival was 12.5 months for VG versus 10.6 months for CG. The overall response rate (ORR) was higher in the VG arm than in the CG arm (63% versus 40%) but was not statistically significant in the intention-to-treat analysis. Furthermore, VG showed a high complete response (CR) rate, 22% versus 3% in CG. In the per-protocol group, both ORR and CR were significantly higher for VG than for CG. The most common adverse events (AEs) were fatigue, haematological toxicities, gastrointestinal disorders and nausea/vomiting. Common grade III/IV AEs were neutropenia (VG 62%, CG 43%), thrombocytopenia (VG 7%, CG 37%) and febrile neutropenia (VG 31%, CG 7%).ConclusionsThe combination of VG did not improve PFS compared with standard treatment with CG in patients unfit for cisplatin due to renal impairment. The response rate of VG indicates, however, an active regimen and warrants further studies.Clinicaltrials.gov numberNCT02665039.
       
  • UCBG 2-04: Long-term results of the PACS 04 trial evaluating adjuvant
           epirubicin plus docetaxel in node-positive breast cancer and trastuzumab
           in the human epidermal growth factor receptor 2–positive subgroup
    • Abstract: Publication date: November 2019Source: European Journal of Cancer, Volume 122Author(s): Véronique D'Hondt, Jean-Luc Canon, Lise Roca, Christelle Levy, Jean-Yves Pierga, Fanny Le Du, Mario Campone, Isabelle Desmoulins, Anthony Goncalves, Marc Debled, Maria Rios, Jean-Marc Ferrero, Daniel Serin, Anne-Claire Hardy-Bessard, Gilles Piot, Etienne Brain, Nadine Dohollou, Hubert Orfeuvre, Jerome Lemonnier, Henri RochéAbstractPurposeWe conducted a double-randomised phase III trial to evaluate a concomitant taxane-anthracycline regimen in node-positive breast cancer and the efficacy of trastuzumab in the human epidermal growth factor receptor 2 (HER2)–positive subpopulation.MethodsA total of 3010 patients with node-positive breast cancer were randomly assigned to receive 6 cycles of 500 mg/m2 of fluorouracil, 100 mg/m2 of epirubicin and 500 mg/m2 of cyclophosphamide (FEC) or 75 mg/m2 of epirubicin and 75 mg/m2 of docetaxel (ED). Patients with HER2-positive tumours were secondary randomly assigned to either trastuzumab or observation. The primary end-point was disease-free survival (DFS) in the two chemotherapy arms.ResultsAfter a 115-month median follow-up, DFS was not significantly better in the ED arm (DFS: 70%, 95% confidence interval [CI]: 67–72) than in the FEC arm (DFS: 68%, 95% CI: 65–70; hazard ratio [HR] = 0.88, 95% CI: 0.77–1.01; p = 0.064). The OS was not different between FEC (OS: 80%, 95% CI: 78–83) and ED (OS: 81%, 95% CI: 79–83); HR = 0.97, 95% CI: 0.81–1.16; p = 0.729). ED appeared more toxic. In the 528 HER2-positive subset, there was trend for a higher DFS, in the intention-to-treat population, in the trastuzumab arm (DFS: 68%, 95% CI: 61–74) than in the observation arm (DFS: 60%, 95% CI: 54–66; HR = 0.77, 95% CI: 0.57–1.03; p = 0.079). In the per-protocol population, DFS was significantly higher in the trastuzumab arm (DFS: 70%, 95% CI: 63–76) than in the observation arm (DFS: 59%, 95% CI: 53–65; HR = 0.69, 95% CI: 0.51–0.94; p = 0.0156). The OS was not different between these 2 arms.ConclusionThis study did not show superiority of the concomitant anthracycline-taxane arm which was more toxic in high-risk node-positive breast cancer patients. Long-term results of the HER2-positive subpopulation are in line with those of the other adjuvant trastuzumab trials but quantitatively less pronounced mostly because of lack of power.
       
  • Haematological immune-related adverse events with immune checkpoint
           inhibitors, how to manage'
    • Abstract: Publication date: November 2019Source: European Journal of Cancer, Volume 122Author(s): J.M. Michot, J. Lazarovici, A. Tieu, S. Champiat, A.L. Voisin, M. Ebbo, B. Godeau, M. Michel, V. Ribrag, O. LambotteAbstractImmune checkpoint inhibitors (ICIs) are changing the treatments of many patients with cancer. These immunotherapies are generally better tolerated than chemotherapy, and their adverse events are immune-related mimicking autoimmune or inflammatory conditions. Although these immune-related adverse events mainly affect the skin, endocrine glands, digestive tract, joints, liver or lungs, all the organs can be theoretically affected, and the haematopoietic system is not spared. This review of the literature will focus on the haematological immune-related adverse events (Haem-irAEs). By reviewing the largest clinical trials of ICIs, we estimate the frequency of Haem-irAEs at 3.6% for all grades and 0.7% for grades III–IV. Frequency of Haem-irAEs of all grades was found to be higher with anti–programmed cell death 1 (4.1%) or anti–programmed cell death ligand 1 (4.7%) than with anti–cytotoxic T-lymphocyte–associated protein 4 (0.5%) (p 
       
  • Outcome of adolescent patients with acute lymphoblastic leukaemia aged
           10–14 years as compared with those aged 15–17 years: Long-term results
           of 1094 patients of the AIEOP-BFM ALL 2000 study
    • Abstract: Publication date: November 2019Source: European Journal of Cancer, Volume 122Author(s): Anna Maria Testi, Andishe Attarbaschi, Maria Grazia Valsecchi, Anja Möricke, Gunnar Cario, Felix Niggli, Daniela Silvestri, Peter Bader, Michaela Kuhlen, Rosanna Parasole, Maria Caterina Putti, Peter Lang, Christian Flotho, Georg Mann, Carmelo Rizzari, Elena Barisone, Franco Locatelli, Christin Linderkamp, Melchior Lauten, Meinolf SuttorpAbstractBackgroundAdolescents (aged 10–17 years) with acute lymphoblastic leukaemia (ALL) have unfavourable disease features and an inferior outcome when compared with younger children, but it is still unclear if differences in disease biology and prognosis exist between adolescents older or younger than 15 years.MethodsWe retrospectively analysed outcomes of 1094 adolescents with ALL, aged 10–17 years, treated within the AIEOP-BFM ALL 2000 trial, overall and by the age groups 10–14 and 15–17 years.FindingsCompared with younger children (aged 1–9 years, n = 3647), adolescents had a statistically inferior 5-year event-free survival (EFS) [74.6% (1.3) vs. 84.4% (0.6)] and overall survival (OS) [83.4% (1.1) vs. 92.7% (0.4); p 
       
  • Cetuximab, fluorouracil and cisplatin with or without docetaxel for
           patients with recurrent and/or metastatic squamous cell carcinoma of the
           head and neck (CeFCiD): an open-label phase II randomised trial
           (AIO/IAG-KHT trial 1108)
    • Abstract: Publication date: November 2019Source: European Journal of Cancer, Volume 122Author(s): K. Klinghammer, T. Gauler, A. Dietz, V. Grünwald, J. Stöhlmacher, S. Knipping, M. Schroeder, O. Guntinas-Lichius, N. Frickhofen, H.-W. Lindeman, R. Fietkau, B. Haxel, C. Große-Thie, G. Maschmeyer, M. Zipfel, P. Martus, M. Knoedler, U. KeilholzAbstractBackgroundThe combination of cisplatin, 5-fluorouracil (5-FU) and cetuximab (PFC) is the reference first-line treatment for recurrent/metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN). We analysed whether treatment intensification by the addition of docetaxel to PFC improved efficacy in R/M SCCHN.MethodsA total of 180 patients with R/M SCCHN (1:1) were assigned to receive either cisplatin (40 mg/m2), docetaxel (40 mg/m2) and 5-FU (2000 mg/m2) at days 1 and 8 and cetuximab (400/250 mg/m2) at days 1, 8 and 15 (DPFC) or standard cisplatin (100 mg/m2) at day 1, 5-FU (1000 mg/m2) at days 1–4 and cetuximab (400/250 mg/m2) at days 1, 8 and 15 (PFC). Chemotherapy was repeated every 21 days and continued for a maximum of 6 cycles in absence of disease progression or limiting toxicity, followed by cetuximab maintenance (500 mg/m2 every 2 weeks). The primary end-point was progression-free survival (PFS).ResultsA preplanned interim analysis for toxicity after 20 patients/arm revealed excessive grade 3 and 4 gastrointestinal (65%) and infectious toxicities (35%) in arm A, which led to dose reduction of cisplatin to 30 mg/m2 and 5-FU to 1000 mg/m2 for subsequent patients. With a median follow-up of 2 years, grade 4 toxicities were 21.3% vs. 30.8% for DPFC and PFC, respectively. More treatment-related deaths occurred with DPFC vs. PFC, with 11.2% and 6.6%, respectively. For DPFC and PFC, the median PFS was 6.3 vs. 6.4 months (hazard ratio [HR] = 0.97, p = 0.87), the median overall survival was 8.9 vs. 10.6 months (HR = 1.29 p = 0.1) and response rates were 38.2% vs. 31.9% (p = 0.9), respectively.ConclusionsDPFC failed to improve efficacy in R/M SCCHN. On the contrary, a high toxicity and mortality rate was detected in both arms, which underscores the vulnerability of patients with R/M SCCHN, and research on the need for further optimisation of the front-line chemotherapy backbone is ongoing.
       
  • Clonal diversity of MYC amplification evaluated by fluorescent in situ
           hybridisation and digital droplet polymerase chain reaction in
           oesophagogastric cancer: Results from a prospective clinical trial
           screening programme
    • Abstract: Publication date: November 2019Source: European Journal of Cancer, Volume 122Author(s): Michael Davidson, Lauren I. Aronson, Julie Howard-Reeves, Hanna Bryant, Rosalind J. Cutts, Sanna Hulkki-Wilson, Kyriakos Kouvelakis, Eftheleria Kalaitzaki, David Watkins, Naureen Starling, Sheela Rao, Marta Llorca Cardenosa, Ruwaida Begum, Isma Rana, Retchel Lazaro-Alcausi, Monica Terlizzo, Andrew Wotherspoon, Gina Brown, John Swansbury, Christopher J. LordAbstractIntroductionThe MYC proto-oncogene is among the most commonly dysregulated genes in human cancers. We report screening data from the iMYC trial, an ongoing phase II study assessing ibrutinib monotherapy in advanced pretreated MYC- and/or HER2-amplified oesophagogastric cancer, representing the first attempt to prospectively identify MYC amplifications in this tumour type for the purposes of therapeutic targeting.MethodsScreening utilising a fluorescent in situ hybridisation (FISH) assay for assessment of tumour MYC amplification has been instituted. An experimental digital droplet polymerase chain reaction (ddPCR) assay to assess MYC amplification in both tumour and circulating-tumour (ct)DNA has been developed and investigated.ResultsOne hundred thirty-five archival tumour specimens have undergone successful FISH analysis with 23% displaying evidence of MYC amplification. Intertumour heterogeneity was observed, with the percentage of cancer cells harbouring MYC amplification ranging widely between samples (median 51%, range 11–94%). Intratumoural clonal diversity of MYC amplification was also observed, with a significant degree of variance in amplification ratios (Bartlett's test for equal variance p 70%) of amplified cells within the tumour specimen but was not reliable in samples containing a low proportion of amplified cells or in ctDNA.ConclusionsOur results illustrate the utility of FISH to assess MYC amplification prospectively for a biomarker-selected trial by providing reliable and reproducible results in real time, with a high degree of heterogeneity of MYC amplification observed. We show that ddPCR can potentially detect high-level MYC amplifications in tumour tissue.
       
  • Preclinical models of breast cancer: Two-way shuttles for immune
           checkpoint inhibitors from and to patient bedside
    • Abstract: Publication date: November 2019Source: European Journal of Cancer, Volume 122Author(s): Amal Kamal Abdel-Aziz, Mona Kamal Saadeldin, Paolo D'Amico, Stefania Orecchioni, Francesco Bertolini, Giuseppe Curigliano, Saverio MinucciAbstractThe Food and Drug Administration has lately approved atezolizumab, anti-programmed death ligand 1 (PD-L1), to be used together with nanoparticle albumin-bound (nab) paclitaxel in treating patients with triple negative breast cancer (BC) expressing PD-L1. Nonetheless, immune checkpoint inhibitors (ICIs) are still challenged by the resistance and immune-related adverse effects evident in a considerable subset of treated patients without conclusive comprehension of the underlying molecular basis, biomarkers and tolerable therapeutic regimens capable of unleashing the anti-tumour immune responses. Stepping back to preclinical models is thus inevitable to address these inquiries. Herein, we comprehensively review diverse preclinical models of BC exploited in investigating ICIs underscoring their pros and cons as well as the learnt and awaited lessons to allow full exploitation of ICIs in BC therapy.
       
  • The transformation of radiation oncology using real-time magnetic
           resonance guidance: A review
    • Abstract: Publication date: November 2019Source: European Journal of Cancer, Volume 122Author(s): William A. Hall, Eric S. Paulson, Uulke A. van der Heide, Clifton D. Fuller, B.W. Raaymakers, Jan J.W. Lagendijk, X. Allen Li, David A. Jaffray, Laura A. Dawson, Beth Erickson, Marcel Verheij, Kevin J. Harrington, Arjun Sahgal, Percy Lee, Parag J. Parikh, Michael F. Bassetti, Clifford G. Robinson, Bruce D. Minsky, Ananya Choudhury, Robert J.H.A. TersteegAbstractRadiation therapy (RT) is an essential component of effective cancer care and is used across nearly all cancer types. The delivery of RT is becoming more precise through rapid advances in both computing and imaging. The direct integration of magnetic resonance imaging (MRI) with linear accelerators represents an exciting development with the potential to dramatically impact cancer research and treatment. These impacts extend beyond improved imaging and dose deposition. Real-time MRI-guided RT is actively transforming the work flows and capabilities of virtually every aspect of RT. It has the opportunity to change entirely the delivery methods and response assessments of numerous malignancies. This review intends to approach the topic of MRI-based RT guidance from a vendor neutral and international perspective. It also aims to provide an introduction to this topic targeted towards oncologists without a speciality focus in RT. Speciality implications, areas for physician education and research opportunities are identified as they are associated with MRI-guided RT. The uniquely disruptive implications of MRI-guided RT are discussed and placed in context. We further aim to describe and outline important future changes to the speciality of radiation oncology that will occur with MRI-guided RT. The impacts on RT caused by MRI guidance include target identification, RT planning, quality assurance, treatment delivery, training, clinical workflow, tumour response assessment and treatment scheduling. In addition, entirely novel research areas that may be enabled by MRI guidance are identified for future investigation.
       
  • Deep and sustained radiological response after MEK-RAF inhibition in HRAS
           mutant apocrine carcinoma of the scalp
    • Abstract: Publication date: November 2019Source: European Journal of Cancer, Volume 122Author(s): Mariana Scaranti, Daniel Nava Rodrigues, Udai Banerji
       
  • The significance of tumour deposits in rectal cancer after neoadjuvant
           therapy: a systematic review and meta-analysis
    • Abstract: Publication date: November 2019Source: European Journal of Cancer, Volume 122Author(s): A.C. Lord, C. Graham Martínez, N. D'Souza, P.H. Pucher, G. Brown, I.D. NagtegaalAbstractBackgroundTumour deposits (TDs) are a poor prognostic marker in colorectal cancer, but their significance after neoadjuvant chemoradiotherapy is less certain because this group of patients is excluded in most studies. Post-treatment TD might even be a sign of tumour response. No previous reviews have assessed outcomes in this group.Materials and methodsA systematic review and meta-analysis was undertaken according to Preferred Reporting for Systematic Reviews and Meta-Analyses guidelines to determine the relevance of post-treatment TD. Inclusion criteria were studies assessing TD in patients who had undergone pre-operative treatment with radiotherapy and/or chemotherapy and reporting prevalence and survival outcomes. Studies that did not include histological review of cases were excluded.ResultsEight studies and 1283 patients were included in the review. Prevalence of TDs varied from 11.8% to 44.2% (mean 23.7%), similar to untreated patients. The presence of TDs after chemoradiotherapy was associated with invasion depth, lymph node involvement, perineural invasion and synchronous metastases. The pooled hazard ratio for 5-year adverse disease–free survival was 2.3 (95% confidence interval [CI]: 1.8–2.9), and that for overall survival was 2.5 (95% CI: 1.9–3.3). One study showed a survival benefit with adjuvant therapy in the TD-positive group.ConclusionsIn analogy with untreated patients, the presence of TDs in patients with rectal cancer after neoadjuvant treatment is associated with advanced disease and a poor outcome.
       
 
 
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