Directional inconsistency between Response Evaluation Criteria in Solid Tumors (RECIST) time to progression and response speed and depth
We seek to characterize how faster tumour shrinkage rate (k) can lead to paradoxically shorter Response Evaluation Criteria in Solid Tumors (RECIST) time to progression ( ‘TTP20’ – tumour size exceeding its minimum by 5 mm and 20%) [1] and, therefore, progression-free survival (PFS). Specifically, we investigate under what conditions this paradoxical behaviour occurs, what fraction of patients satisfy these conditions, whether this phenomenon can invert popul ation-level PFS hazard ratio, and consistency of an alternative time-to-event benefit metric with k. (Source: European Journal of Cancer)
Source: European Journal of Cancer - February 7, 2019 Category: Cancer & Oncology Authors: Kaitlyn Johnson, Axel Gomez, Jackson Burton, Douglas White, Arijit Chakravarty, Annette Schmid, Dean Bottino Tags: Original Research Source Type: research

State of clinical research of radiotherapy/chemoradiotherapy and immune checkpoint inhibitor therapy combinations in solid tumours —a German radiation oncology survey
Combinations of immune checkpoint inhibitors (ICIs) with radiotherapy and/or chemoradiotherapy are currently under investigation in many cancer types and clinical settings. In this survey, we solicited members of the German Radiation Oncology Society and young DEGRO (working group of DEGRO e.V.) to review the current status of research in this field and underline critical issues such as oncological benefit, treatment toxicity and obstacles in clinical research. The responses represent 14 different departments of radiation oncology at German university hospitals. (Source: European Journal of Cancer)
Source: European Journal of Cancer - January 14, 2019 Category: Cancer & Oncology Authors: Lukas K äsmann, Chukwuka Eze, Maurice Dantes, Olarn Roengvoraphoj, Maximilian Niyazi, Claus Belka, Farkhad Manapov Tags: Current Perspective Source Type: research

Randomised phase 2 study of pembrolizumab plus CC-486 versus pembrolizumab plus placebo in patients with previously treated advanced non-small cell lung cancer
Preclinical and early clinical studies suggest that combining epigenetic agents with checkpoint inhibitors can potentially improve outcomes in patients with previously treated advanced non-small cell lung cancer (NSCLC). This phase 2 trial examined second-line pembrolizumab  + CC-486 (oral azacitidine) in patients with advanced NSCLC. (Source: European Journal of Cancer)
Source: European Journal of Cancer - January 14, 2019 Category: Cancer & Oncology Authors: Benjamin P. Levy, Giuseppe Giaccone, Benjamin Besse, Enriqueta Felip, Marina Chiara Garassino, Manuel Domine Gomez, Pilar Garrido, Bilal Piperdi, Santiago Ponce-Aix, Daniel Menezes, Kyle J. MacBeth, Alberto Risue ño, Ruta Slepetis, Xiaoling Wu, Abderrahi Tags: Original Research Source Type: research

TERT promoter mutations identify a high-risk group in metastasis-free advanced thyroid carcinoma
TERT promoter mutations are associated with adverse clinicopathological characteristics in thyroid carcinomas and considered as a major indicator of poor outcomes. Nevertheless, most studies have pooled heterogeneous types of thyroid carcinomas  and have been conducted retrospectively. We investigated the association between TERT promoter mutations and recurrence in a prospective series of 173 intermediate- to high-risk patients with thyroid cancer. (Source: European Journal of Cancer)
Source: European Journal of Cancer - January 14, 2019 Category: Cancer & Oncology Authors: Claire Bournaud, Fran çoise Descotes, Myriam Decaussin-Petrucci, Julien Berthiller, Christelle de la Fouchardière, Anne-Laure Giraudet, Mireille Bertholon-Gregoire, Philip Robinson, Jean-Christophe Lifante, Jonathan Lopez, Françoise Borson-Chazot Tags: Original Research Source Type: research

Phase 2 placebo-controlled, single-blind trial to evaluate the impact of oral ibandronate on bone mineral density in osteopenic breast cancer patients receiving adjuvant aromatase inhibitors: 5-year results of the single-centre BONADIUV trial
We present the final results of the BONADIUV trial, a single-blind, randomised, placebo-controlled phase 2 study to evaluate the impact of ibandronate treatment on bone mineral density (BMD) in osteopenic women taking aromatase inhibitors (AI). (Source: European Journal of Cancer)
Source: European Journal of Cancer - January 14, 2019 Category: Cancer & Oncology Authors: Lorenzo Livi, Vieri Scotti, Isacco Desideri, Calogero Saieva, Sara Cecchini, Giulio Francolini, Carlotta Becherini, Camilla Delli Paoli, Luca Visani, Viola Salvestrini, Maria Laura De Feo, Jacopo Nori, Marco Bernini, Luis Sanchez, Lorenzo Orzalesi, Simone Tags: Clinical Trial Source Type: research

The efficacy and safety of sunitinib given on an individualised schedule as first-line therapy for metastatic renal cell carcinoma: A phase 2 clinical trial
Sunitinib is administered on a rigid schedule that may not be optimal for all patients. We hypothesised that toxicity-driven dose and schedule changes would optimise drug exposure and outcome for each patient. (Source: European Journal of Cancer)
Source: European Journal of Cancer - January 14, 2019 Category: Cancer & Oncology Authors: Georg A. Bjarnason, Jennifer J. Knox, Christian K. Kollmannsberger, Denis Soulieres, D. Scott Ernst, Pawel Zalewski, Christina M. Canil, Eric Winquist, Sebastien J. Hotte, Scott A. North, Daniel Yick Chin Heng, Robyn Jane Macfarlane, Peter M. Venner, Anil Tags: Clinical Trial Source Type: research

NAPOLI-1 phase 3 study of liposomal irinotecan in metastatic pancreatic cancer: Final overall survival analysis and characteristics of long-term survivors
Liposomal irinotecan (nal-IRI) plus 5-fluorouracil and leucovorin (5-FU/LV) is approved for patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) previously treated with gemcitabine-based therapy. This approval was based on significantly improved median overall survival compared with 5-FU/LV alone (6.1 vs 4.2 months; hazard ratio [HR], 0.67) in the global phase 3 NAPOLI-1 trial. Here, we report the final survival analysis and baseline characteristics associated with long-term survivors (survival of ≥1 year) in the NAPOLI-1 trial. (Source: European Journal of Cancer)
Source: European Journal of Cancer - January 14, 2019 Category: Cancer & Oncology Authors: Andrea Wang-Gillam, Richard A. Hubner, Jens T. Siveke, Daniel D. Von Hoff, Bruce Belanger, Floris A. de Jong, Beloo Mirakhur, Li-Tzong Chen Tags: Original Research Source Type: research

Stromal lymphocyte infiltration is associated with tumour invasion depth but is not prognostic in high-grade T1 bladder cancer
The objective of the present study was to investigate the association of stromal lymphocytic infiltration with clinicopathological parameters and their correlation with outcomes in patients with high-grade pT1 non–muscle-invasive bladd er cancer (NMIBC). (Source: European Journal of Cancer)
Source: European Journal of Cancer - January 14, 2019 Category: Cancer & Oncology Authors: Mathieu Rouanne, Reem Betari, Cam élia Radulescu, Aïcha Goubar, Nicolas Signolle, Yann Neuzillet, Yves Allory, Aurélien Marabelle, Julien Adam, Thierry Lebret Tags: Original Research Source Type: research

Neoepitopes-based vaccines: challenges and perspectives
First generations of cancer vaccines using shared tumour antigens have been associated with disappointing clinical results. However, the paradigm shift introduced by immune checkpoint inhibitors has led to a renewed interest on anti-tumoural vaccination based on mutation-associated neoantigens. First clinical results are encouraging with some signs of clinical activity associated with induction of a specific immune response. In advanced or metastatic diseases, vaccination may either enhance the response to Programmed cell death 1 (PD-1/-L1) antagonists by increasing the number of effectors within the tumour or induce an an...
Source: European Journal of Cancer - January 14, 2019 Category: Cancer & Oncology Authors: Vincent Alcazer, Paola Bonaventura, Laurie Tonon, Sandrine Wittmann, Christophe Caux, St éphane Depil Tags: Current Perspective Source Type: research

Immunotherapy comes of age in octagenarian and nonagenarian metastatic melanoma patients
We describe a cohort of 144 patients ≥65 ye ars and analyse the efficacy and toxicity of anti–PD-1 therapy in ages 80–100 years compared with ages 65–79 years. Records of metastatic melanoma patients aged 65–100 years treated with anti–PD-1 were collected retrospectively. (Source: European Journal of Cancer)
Source: European Journal of Cancer - January 14, 2019 Category: Cancer & Oncology Authors: Guy Ben-Betzalel, Yael Steinberg-Silman, Ronen Stoff, Nethanel Asher, Ronnie Shapira-Frommer, Jacob Schachter, Gal Markel Tags: Original Research Source Type: research

Adjuvant chemotherapy in patients with rectal cancer achieving pathologic complete response after neoadjuvant chemoradiation and surgery
The intensification of neoadjuvant therapies (i.e., chemoradiotherapy [CTRT] before surgery has provided a shift in the paradigm of treatment of locally advanced rectal cancer [1]. More recently, despite the short follow-up of published studies [2], the preoperative addition of full doses of induction systemic chemotherapy before CTRT is emerging as a potential new standard of care. (Source: European Journal of Cancer)
Source: European Journal of Cancer - January 14, 2019 Category: Cancer & Oncology Authors: Gianluca Tomasello, Michele Ghidini, Fausto Petrelli Tags: Letter to the Editor Source Type: research

Circulating innate immune markers and outcomes in treatment-na ïve advanced non–small cell lung cancer patients
Innate immunity represents the first step of activation of the immune system and dictates the quality of adaptive immune responses. Studies have reported links between systemic inflammatory or innate immune markers and prognosis in patients with lung cancer. To our knowledge, the prospective and concomitant study of these systemic markers has never been performed. (Source: European Journal of Cancer)
Source: European Journal of Cancer - January 14, 2019 Category: Cancer & Oncology Authors: M. Charrier, L. Mezquita, B. Lueza, L. Dupraz, D. Planchard, J. Remon, C. Caramella, L. Cassard, L. Boselli, K.S. Reiners, E. Pogge von Strandmann, S. Rusakiewicz, R. Ferrara, B. Duchemann, M. Naigeon, J.P. Pignon, B. Besse, N. Chaput Tags: Original Research Source Type: research

A multinational, multi-tumour basket study in very rare cancer types: The European Organization for Research and Treatment of Cancer phase II 90101 ‘CREATE’ trial
Until recently, clinical trials investigating cancer drugs have been conducted separately for different tumour location and histological types  because they were the primary known determinant of drug efficacy. With the development of therapies targeting genomic alterations in tumour cells, novel clinical development strategies are necessary. Indeed, the genomic alteration can be uncommon in one particular tumour type and can be shared by several tumour types. Basket trials typically include patients with diverse tumour types sharing one distinguishing feature (i.e. (Source: European Journal of Cancer)
Source: European Journal of Cancer - January 14, 2019 Category: Cancer & Oncology Authors: Julien P éron, Sandrine Marreaud, Dominiek Staelens, Tiana Raveloarivahy, Axelle Nzokirantevye, Jocelyne Flament, Jonathan Steuve, Michela Lia, Laurence Collette, Patrick Schöffski Tags: EORTC Clinical Trial in Perspective Source Type: research

Second-line targeted therapies after nivolumab-ipilimumab failure in metastatic renal cell carcinoma
Nivolumab-ipilimumab demonstrated a survival benefit over sunitinib in first-line setting for metastatic renal cell carcinomas (mRCCs) and is becoming a new standard of care for na ïve patients with intermediate or poor risk prognosis (International mRCC Database Consortium). The efficacy of subsequent vascular endothelial growth factor receptor tyrosine kinase inhibitors (TKIs) after nivolumab-ipilimumab failure remains unclear. (Source: European Journal of Cancer)
Source: European Journal of Cancer - January 5, 2019 Category: Cancer & Oncology Authors: Marie Auvray, Edouard Auclin, Philippe Barthelemy, Petri Bono, Pirkko Kellokumpu-Lehtinen, Marine Gross-Goupil, Guillermo De Velasco, Thomas Powles, Guillaume Mouillet, Yann-Alexandre Vano, Gwena ëlle Gravis, Loïc Mourey, Franck Priou, Frédéric Rollan Tags: Original Research Source Type: research

The real-world impact of modern treatments on the survival of patients with metastatic melanoma
Between 2010 and 2015, pivotal trials with strict enrolment criteria led to the approval of several new treatments for metastatic melanoma (MM). We sought to determine the impact of these treatments in the ‘real world’. We took advantage of the Danish MM database (DAMMED), which contains data on the entire, unselected population diagnosed with MM within Denmark. All MM cases (excluding ocular MM, n = 837) diagnosed in three non-consecutive years marked by major changes in the first-line treatme nts (2012: interleukin-2 and BRAF inhibitors; 2014: anti–CTLA-4: Cytotoxic T-Lymphocyte Antigen 4...
Source: European Journal of Cancer - December 31, 2018 Category: Cancer & Oncology Authors: Marco Donia, Eva Ellebaek, Trine Heide Øllegaard, Lone Duval, Jens Bull Aaby, Lise Hoejberg, Ulrich Heide Køhler, Henrik Schmidt, Lars Bastholt, Inge Marie Svane Tags: Original Research Source Type: research

A phase II, randomised study of mFOLFOX6 with or without the Akt inhibitor ipatasertib in patients with locally advanced or metastatic gastric or gastroesophageal junction cancer
Akt activation is common in gastric/gastroesophageal junction cancer (GC/GEJC) and is associated with chemotherapy resistance. Treatment with ipatasertib, a pan-Akt inhibitor, may potentiate the efficacy of chemotherapy in GC/GEJC. (Source: European Journal of Cancer)
Source: European Journal of Cancer - December 25, 2018 Category: Cancer & Oncology Authors: Y.-J. Bang, Y.-K. Kang, M. Ng, H.C. Chung, Z.A. Wainberg, S. Gendreau, W.Y. Chan, N. Xu, D. Maslyar, R. Meng, I. Chau, J.A. Ajani Tags: Original Research Source Type: research

Planned organ preservation for early T2-3 rectal adenocarcinoma: A French, multicentre study
Combining CXB and nCRT in selected early T2-T3 rectal cancers may safely provide a high rate of cCR, organ preservation, and good bowel function with a risk of local recurrence below 15%. Such an approach could be offered to operable patients as a planned option for organ preservation. (Source: European Journal of Cancer)
Source: European Journal of Cancer - December 20, 2018 Category: Cancer & Oncology Authors: Jean-Pierre G érard, Nicolas Barbet, Jocelyn Gal, Catherine Dejean, Ludovic Evesque, Jérôme Doyen, Régis Coquard, Jean Gugenheim, Emmanuel Benizri, Renaud Schiappa, Guillaume Baudin, Karène Benezery, Eric François Tags: Original Research Source Type: research

An open-label, multicentre safety study of vemurafenib in patients with BRAFV600-mutant metastatic melanoma: final analysis and a validated prognostic scoring system
The oncogenic BRAF inhibitor vemurafenib improves outcomes for patients with advanced BRAFV600 mutation-positive melanoma compared with cytotoxic chemotherapy. Vemurafenib is now approved for use in this patient population. (Source: European Journal of Cancer)
Source: European Journal of Cancer - December 20, 2018 Category: Cancer & Oncology Authors: James Larkin, Michael P. Brown, Ana M. Arance, Axel Hauschild, Paola Queirolo, Michele Del Vecchio, Paolo A. Ascierto, Ivana Krajsov á, Jacob Schachter, Bart Neyns, Claus Garbe, Vanna Chiarion Sileni, Mario Mandalà, Helen Gogas, Enrique Espinosa, Geke H Tags: Original Research Source Type: research

Refining the selection of patients with metastatic colorectal cancer for treatment with temozolomide using proteomic analysis of O6-methylguanine-DNA-methyltransferase
The repair enzyme O6-methylguanine-DNA-methyltransferase (MGMT) is a validated predictor of benefit from temozolomide (TMZ) in glioblastoma. However, only 10% of patients with MGMT-methylated metastatic colorectal cancer (mCRC) respond to TMZ. (Source: European Journal of Cancer)
Source: European Journal of Cancer - December 19, 2018 Category: Cancer & Oncology Authors: Sarit Schwartz, Chris Szeto, Yuan Tian, Fabiola Cecchi, Salvatore Corallo, Maria Alessandra Calegari, Maria Di Bartolomeo, Federica Morano, Alessandra Raimondi, Giovanni Fuc à, Antonia Martinetti, Ivana De Pascalis, Maurizio Martini, Antonino Belfiore, M Tags: Original Research Source Type: research

General population normative data for the EORTC QLQ-C30 health-related quality of life questionnaire based on 15,386 persons across 13 European countries, Canada and the Unites States
This study aimed at systematically collecting norm data from the general population to develop European QLQ-C30 norm scores and to generate comparable norm data for individual countries in Europe and North America. (Source: European Journal of Cancer)
Source: European Journal of Cancer - December 19, 2018 Category: Cancer & Oncology Authors: S. Nolte, G. Liegl, M.A. Petersen, N.K. Aaronson, A. Costantini, P.M. Fayers, M. Groenvold, B. Holzner, C.D. Johnson, G. Kemmler, K.A. Tomaszewski, A. Waldmann, T.E. Young, M. Rose, the EORTC Quality of Life Group Tags: Original Research Source Type: research

Durvalumab for recurrent or metastatic head and neck squamous cell carcinoma: Results from a single-arm, phase II study in patients with ≥25% tumour cell PD-L1 expression who have progressed on platinum-based chemotherapy
Patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) progressing on platinum-based chemotherapy have poor prognoses and limited therapeutic options. Programmed cell death-1 (PD-1) and its ligand 1 (PD-L1) are frequently upregulated in HNSCC. The international, multi-institutional, single-arm, phase II HAWK study (NCT02207530) evaluated durvalumab monotherapy, an anti-PD-L1 monoclonal antibody, in PD-L1-high patients with platinum-refractory R/M HNSCC. (Source: European Journal of Cancer)
Source: European Journal of Cancer - December 18, 2018 Category: Cancer & Oncology Authors: Dan P. Zandberg, Alain P. Algazi, Antonio Jimeno, James S. Good, J érôme Fayette, Nathaniel Bouganim, Neal E. Ready, Paul M. Clement, Caroline Even, Raymond W. Jang, Stuart Wong, Ulrich Keilholz, Jill Gilbert, Moon Fenton, Irene Braña, Stephanie Henry, Tags: Original Research Source Type: research

Establishing the European Norm for the health-related quality of life domains of the computer-adaptive test EORTC CAT Core
This study aimed at establishing the European Norm for each CAT domain based on general population data. (Source: European Journal of Cancer)
Source: European Journal of Cancer - December 18, 2018 Category: Cancer & Oncology Authors: G. Liegl, M.A. Petersen, M. Groenvold, N.K. Aaronson, A. Costantini, P.M. Fayers, B. Holzner, C.D. Johnson, G. Kemmler, K.A. Tomaszewski, A. Waldmann, T.E. Young, M. Rose, S. Nolte, the EORTC Quality of Life Group Tags: Original Research Source Type: research

Randomised phase II study of second-line olaratumab with mitoxantrone/prednisone versus mitoxantrone/prednisone alone in metastatic castration-resistant prostate cancer
Platelet-derived growth factor receptor- α (PDGFRα) is expressed in primary prostate adenocarcinoma and in associated skeletal metastases. Olaratumab is a fully human monoclonal antibody that binds PDGFRα and blocks downstream signalling. This phase II study assessed the efficacy and safety of olaratumab in combination with mitoxantrone and prednisone (M/P) versus M/P alone in patients with metastatic castration-resistant prostate cancer (mCRPC) who progressed after docetaxel. (Source: European Journal of Cancer)
Source: European Journal of Cancer - December 17, 2018 Category: Cancer & Oncology Authors: Oliver W. Hakenberg, Jose Luis Perez-Gracia, Daniel Castellano, Tomasz Demkow, Tarek Ali, Orazio Caffo, Axel Heidenreich, Wolfgang Schultze-Seemann, Brieuc Sautois, Ivan Pavlik, Amy Qin, Ruslan D. Novosiadly, Ashwin Shahir, Robert Ilaria, Johannes Nippgen Tags: Original Research Source Type: research

Reviewers 2018
The Editors of the European Journal of Cancer would like to take this opportunity to express their gratitude to all of the individuals who acted as reviewers in the year 2018. Particular thanks are due to: (Source: European Journal of Cancer)
Source: European Journal of Cancer - December 15, 2018 Category: Cancer & Oncology Source Type: research

Long-term survival in patients with advanced non –small-cell lung cancer treated with atezolizumab versus docetaxel: Results from the randomised phase III OAK study
Atezolizumab (anti –programmed death-ligand 1 [PD-L1]) received approval from the US Food and Drug Administration and European Medicines Agency for previously treated advanced non–small-cell lung cancer based on OAK—a randomised, phase III trial that showed significantly improved survival with atezolizumab versu s docetaxel regardless of PD-L1 expression. With longer follow-up, we summarised the characteristics of long-term survivors (LTSs). (Source: European Journal of Cancer)
Source: European Journal of Cancer - December 15, 2018 Category: Cancer & Oncology Authors: J. von Pawel, R. Bordoni, M. Satouchi, L. Fehrenbacher, M. Cobo, J.Y. Han, T. Hida, D. Moro-Sibilot, P. Conkling, D.R. Gandara, A. Rittmeyer, M. Gandhi, W. Yu, C. Matheny, H. Patel, A. Sandler, M. Ballinger, M. Kowanetz, K. Park Tags: Original Research Source Type: research

Association of quality of life with disease characteristics and treatment outcomes in patients with advanced gastric cancer: Exploratory analysis of RAINBOW and REGARD phase III trials
Inadequate understanding of interpretation of quality of life (QoL) instruments leads to unsatisfactory data reporting and clinical decision-making, including in gastric cancer care. (Source: European Journal of Cancer)
Source: European Journal of Cancer - December 14, 2018 Category: Cancer & Oncology Authors: Ian Chau, Charles S. Fuchs, Atsushi Ohtsu, Afsaneh Barzi, Astra M. Liepa, Zhanglin Lin Cui, Yanzhi Hsu, Salah-Eddin Al-Batran Tags: Original Research Source Type: research

Role of CCL5 and CCR5 gene polymorphisms in epidermal growth factor receptor signalling blockade in metastatic colorectal cancer: analysis of the FIRE-3 trial
Epidermal growth factor receptor signalling blockade increases CCL5 expression that regulates either the anti-tumour immune response or tumour progression. We investigated the potential role of CCL5/CCR5 axis in cetuximab-based treatment in metastatic colorectal cancer (mCRC) patients. (Source: European Journal of Cancer)
Source: European Journal of Cancer - December 13, 2018 Category: Cancer & Oncology Authors: Mitsukuni Suenaga, Sebastian Stintzing, Shu Cao, Wu Zhang, Dongyun Yang, Yan Ning, Satoshi Okazaki, Martin D. Berger, Yuji Miyamoto, Marta Schirripa, Shivani Soni, Afsaneh Barzi, Volker Heinemann, Heinz-Josef Lenz Tags: Original Research Source Type: research

Development of mild drug-induced sclerosing cholangitis after discontinuation of nivolumab
Immune check point inhibitors (ICIs) have shown remarkable success in medical oncology and are being used in many types of tumours including non –small-cell lung carcinoma (NSCLC). However, activation of host T cells can cause immune-related adverse events (irAEs), which can make treatment decisions difficult. Immune-related liver injury is a common form of irAEs and is known to occur in 1–3% of patients treated with ICIs [1]. In contras t, only eight cases of immune-related cholangitis have been reported, most of whom required extensive treatment [2–7]. (Source: European Journal of Cancer)
Source: European Journal of Cancer - December 13, 2018 Category: Cancer & Oncology Authors: Shoko Noda-Narita, Suguru Mizuno, Satoshi Noguchi, Kousuke Watanabe, Yousuke Nakai, Kazuhiko Koike, Hidenori Kage, Takahide Nagase Tags: Letter to the Editor Source Type: research

Dramatic response of nivolumab-associated psoriasiform dermatitis to etoposide
There is a revolution in cancer therapy prompted by the resurgence of immunotherapy in the form of immune checkpoint inhibitors (ICPis) [1]. With the beneficial effects of this new understanding of how to harness the prowess of the immune system with therapeutic intent, it has also become clear that similar  to other modalities of cancer therapy, there are important side-effects associated to their use [2]. These side-effects are known as immune-related adverse events (irAEs) and are the result of an immunological imbalance introduced by the disruption of the immune system homoeostasis. (Source: European Journal of Cancer)
Source: European Journal of Cancer - December 13, 2018 Category: Cancer & Oncology Authors: Adan Rios, Putao Cen, Brian Dinh, Steven R. Mays, Anisha B. Patel Tags: Letter to the Editor Source Type: research

Topographical distribution of sentinel nodes and metastases from T1 –T2 oral squamous cell carcinomas
The objective is to investigate the topographical distribution of sentinel nodes (SNs) and lymph node metastases in T1-2cN0 oral squamous cell carcinomas (OSCCs). (Source: European Journal of Cancer)
Source: European Journal of Cancer - December 12, 2018 Category: Cancer & Oncology Authors: Jacob M ølstrøm, Mark Grønne, Anders Green, Vivi Bakholdt, Jens Ahm Sørensen Tags: Original Research Source Type: research

Common genetic variants contribute to incomplete penetrance: evidence from cancer-free BRCA1 mutation carriers
The presence of pathogenic germline mutation in BRCA1 gene is considered as the most penetrant genetic predisposition for breast cancer. However, a portion of BRCA1 mutation carriers never develops breast cancer throughout their lifetime. This phenomenon is called incomplete penetrance. Genetic factor is proposed to contribute to this phenomenon, but the details regarding the genetic factor remain elusive. BRCA1 mutations were inherited from the ancestors of the mutation carrier families during human evolution, and their presence is a consistent threat to the survival of the mutation carrier population. (Source: European Journal of Cancer)
Source: European Journal of Cancer - December 11, 2018 Category: Cancer & Oncology Authors: Bradley Downs, Simon Sherman, Jian Cui, Yeong C. Kim, Carrie Snyder, Maria Christensen, Jiangtao Luo, Henry Lynch, San Ming Wang Tags: Original Research Source Type: research

Prognosis of renal cell carcinoma with bone metastases: Experience from a large cancer centre
Bone metastases (BMs) are associated with significant morbidity and shorter survival in renal cell carcinoma (RCC). Our purpose was to identify prognostic factors for overall survival (OS) in RCC patients with BMs. (Source: European Journal of Cancer)
Source: European Journal of Cancer - December 11, 2018 Category: Cancer & Oncology Authors: F. Ruatta, L. Derosa, B. Escudier, E. Colomba, A. Guida, G. Baciarello, Y. Loriot, K. Fizazi, L. Albiges Tags: Original Research Source Type: research

A cost analysis of upfront DPYD genotype –guided dose individualisation in fluoropyrimidine-based anticancer therapy
Fluoropyrimidine therapy including capecitabine or 5-fluorouracil can result in severe treatment-related toxicity in up to 30% of patients. Toxicity is often related to reduced activity of dihydropyrimidine dehydrogenase, the main metabolic fluoropyrimidine enzyme, primarily caused by genetic DPYD polymorphisms. In a large prospective study, it was concluded that upfront DPYD-guided dose individualisation is able to improve safety of fluoropyrimidine-based therapy. In our current analysis, we evaluated whether this strategy is cost saving. (Source: European Journal of Cancer)
Source: European Journal of Cancer - December 11, 2018 Category: Cancer & Oncology Authors: Linda M. Henricks, Carin A.T.C. Lunenburg, Femke M. de Man, Didier Meulendijks, Geert W.J. Frederix, Emma Kienhuis, Geert-Jan Creemers, Arnold Baars, Vincent O. Dezentj é, Alexander L.T. Imholz, Frank J.F. Jeurissen, Johanna E.A. Portielje, Rob L.H. Jans Tags: Original Research Source Type: research

Changes in FIT values below the threshold of positivity and short-term risk of advanced colorectal neoplasia: Results from a population-based cancer screening program
Increased values in the fecal immunochemical test (FIT) are correlated with increasingly severe colorectal neoplasia, but little attention has been given to FIT values below the cut-off point (negative FIT, nFIT). We analysed the relationship between the concentrations of two consecutive nFIT and the risk of following screen-detected advanced neoplasia and interval cancer (IC) in a population-based colorectal cancer screening program. (Source: European Journal of Cancer)
Source: European Journal of Cancer - December 10, 2018 Category: Cancer & Oncology Authors: Andrea Buron, Marta Rom án, Josep M. Augé, Francesc Macià, Jaume Grau, Maria Sala, Javier Louro, Montserrat Martinez-Alonso, Cristina Alvarez-Urturi, Montserrat Andreu, Xavier Bessa, Diana Zaffalon, Antoni Castells, Maria Pellisé, Marta Aldea, Liseth Tags: Original Research Source Type: research

SWITCH II: Phase III randomized, sequential, open-label study to evaluate the efficacy and safety of sorafenib-pazopanib versus pazopanib-sorafenib in the treatment of advanced or metastatic renal cell carcinoma (AUO AN 33/11)
This trial compared the sequential therapy with the multikinase inhibitor sorafenib (So) followed by pazopanib (Pa) or vice versa in advanced/metastatic renal cell carcinoma (mRCC) patients. (Source: European Journal of Cancer)
Source: European Journal of Cancer - December 7, 2018 Category: Cancer & Oncology Authors: Margitta Retz, Jens Bedke, Martin B ögemann, Marc-Oliver Grimm, Uwe Zimmermann, Lothar Müller, Christian Leiber, Dogu Teber, Manfred Wirth, Christian Bolenz, Robbert van Alphen, Maria De Santis, Aart Beeker, Jan Lehmann, Martin Indorf, Melanie Frank, Ca Tags: Clinical Trial Source Type: research

Contrast enhancement is a prognostic factor in IDH1/2 mutant, but not in wild-type WHO grade II/III glioma as confirmed by machine learning
Mutation of the isocitrate dehydrogenase (IDH) gene and co-deletion on chromosome 1p/19q is becoming increasingly relevant for the evaluation of clinical outcome in glioma. Among the imaging parameters, contrast enhancement (CE) in WHO II/III glioma has been reported to indicate poor outcome in the past. We aimed at  reassessing the prognostic value of CE in these tumours within the framework of molecular markers using a machine learning approach (random survival forests [RSF]) as well as conventional Cox regression modelling. (Source: European Journal of Cancer)
Source: European Journal of Cancer - December 7, 2018 Category: Cancer & Oncology Authors: Bogdana Suchorska, Ulrich Sch üller, Annamaria Biczok, Markus Lenski, Nathalie L. Albert, Armin Giese, Friedrich-Wilhelm Kreth, Birgit Ertl-Wagner, Jörg-Christian Tonn, Michael Ingrisch Tags: Original Research Source Type: research

Oxaliplatin, 5-Fluorouracil and Nab-paclitaxel as perioperative regimen in patients with resectable gastric adenocarcinoma: A GERCOR phase II study (FOXAGAST)
The objective was to evaluate the efficacy of Nab-paclitaxel in combination with FOLFOX for RGA patients. (Source: European Journal of Cancer)
Source: European Journal of Cancer - December 7, 2018 Category: Cancer & Oncology Authors: S. Watson, C. de la Fouchardi ère, S. Kim, R. Cohen, J.B. Bachet, C. Tournigand, J.M. Ferraz, M. Lefevre, D. Colin, M. Svrcek, A. Meurisse, C. Louvet Tags: Original Research Source Type: research

A novel risk calculator to predict outcome after surgery for symptomatic spinal metastases; use of a large prospective patient database to personalise surgical management
Surgery for spinal metastases can improve symptoms, but sometimes complications can negate the benefits. Operations may have different indications, complexities and risks, and the choice for an individual is a tailor-made personalised decision. Previous prognostic scoring systems are becoming out of date and inaccurate. We designed a risk calculator to estimate survival after surgery, to inform clinicians and patients when making management decisions. (Source: European Journal of Cancer)
Source: European Journal of Cancer - December 7, 2018 Category: Cancer & Oncology Authors: David Choi, Menelaos Pavlou, Rumana Omar, Mark Arts, Laurent Balabaud, Jacob Maciej Buchowski, Cody Bunger, Chun Kee Chung, Maarten Hubert Coppes, Bart Depreitere, Michael George Fehlings, Norio Kawahara, Chong-Suh Lee, YeeLing Leung, Juan Antonio Martin- Tags: Original Research Source Type: research

Delayed immune-related adverse events in assessment for dose-limiting toxicity in early phase immunotherapy trials
Immunotherapy (IO) agents can cause late-onset immune-related adverse events (irAEs). In phase I trials, observation for dose-limiting toxicities (DLTs) is typically limited to the first cycle. The incidence of delayed-onset DLTs and their potential impact on dose determination have not been fully elucidated. (Source: European Journal of Cancer)
Source: European Journal of Cancer - December 6, 2018 Category: Cancer & Oncology Authors: Y. Kanjanapan, D. Day, M.O. Butler, L. Wang, A.M. Joshua, D. Hogg, N.B. Leighl, A.R. Abdul Razak, A.R. Hansen, S. Boujos, M. Chappell, K. Chow, B. Sherwin, L.-A. Stayner, L. Soultani, A. Zambrana, L.L. Siu, P.L. Bedard, A. Spreafico Tags: Original Research Source Type: research

Human leukocyte antigen variation is associated with adverse events of checkpoint inhibitors
Checkpoint inhibitors (CIs) are highly effective but can induce severe immune-related adverse events (irAEs), which cannot be predicted. We investigated whether human leukocyte antigen (HLA) genes predispose to developing of irAEs during therapy and thus hold a predictive role. (Source: European Journal of Cancer)
Source: European Journal of Cancer - December 6, 2018 Category: Cancer & Oncology Authors: Omar Hasan Ali, Fiamma Berner, David Bomze, Mirjam F ässler, Stefan Diem, Antonio Cozzio, Markus Jörger, Martin Früh, Christoph Driessen, Tobias L. Lenz, Lukas Flatz Tags: Original Research Source Type: research

Microscopically positive resection margin after hepatoblastoma resection: what is the impact on prognosis? A Childhood Liver Tumours  Strategy Group (SIOPEL) report
To evaluate the impact of a microscopically positive resection margin (microPRM) on the outcome of hepatoblastoma patients pretreated with chemotherapy. (Source: European Journal of Cancer)
Source: European Journal of Cancer - December 5, 2018 Category: Cancer & Oncology Authors: Daniel C. Aronson, V íola B. Weeda, Rudolf Maibach, Piotr Czauderna, Patrizia Dall’Igna, Jean de Ville de Goyet, Sophie Branchereau, Giorgio Perilongo, Penelope Brock, Joszef Zsiros, Michaela Semeraro, Christophe Chardot, Barbara Wildhaber, Bruce Morla Tags: Original Research Source Type: research

Diet-dependent toxicity of ipilimumab in metastatic melanoma
The anti –cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody ipilimumab is approved by the Food and Drug Administration (FDA) as one of the main therapeutic agents for treatment of melanoma [1,2]. Its use can lead to long-term remission but also risks inducing immune-related side effects [3]. A lthough most adverse events are mild, the most common severe and potentially life-threatening adverse event is the development of gastrointestinal toxicity. Common terminology criteria for adverse events (CTCAE) ≥ grade 2 diarrhoea occurs in 35% of patients treated with ipilimumab, including cas es...
Source: European Journal of Cancer - December 5, 2018 Category: Cancer & Oncology Authors: P. Majenka, M. Hoffmann, I. R ötzer, A. Dimitrakopoulou-Strauss, R. Koschny, T. Longerich, A. Enk, J.C. Hassel Tags: Letter to the Editor Source Type: research

Impact of anti-thymocyte globulin on results of allogeneic peripheral blood stem cell transplantation for patients with Philadelphia-positive acute lymphoblastic leukaemia: An analysis by the Acute Leukemia Working Party of the EBMT
Anti-thymocyte globulin (ATG) is widely used to prevent graft-versus-host disease (GVHD) after allogeneic peripheral blood stem cell transplantation (alloPBSCT). The goal of this study was to retrospectively assess the effect of ATG on outcomes in the setting of Philadelphia chromosome-positive acute lymphoblastic leukaemia (Ph+  ALL). (Source: European Journal of Cancer)
Source: European Journal of Cancer - December 5, 2018 Category: Cancer & Oncology Authors: Sebastian Giebel, Myriam Labopin, Tomasz Czerw, G érard Socié, Didier Blaise, Ardeshir Ghavamzadeh, Jacob Passweg, Per Ljungman, Xavier Poiré, Patrice Chevallier, Péter Reményi, Alessandro Rambaldi, Boris Anafasyev, Nathalie Fegueux, Montserrat Rovir Tags: Original Research Source Type: research

Performance of the Food and Drug Administration/EMA-approved programmed cell death ligand-1 assays in urothelial carcinoma with emphasis on therapy stratification for first-line use of atezolizumab and pembrolizumab
Recently, the Food and Drug Administration (FDA)/European Medicines Agency (EMA) restricted first-line use of atezolizumab and pembrolizumab in patients with metastasised urothelial carcinoma by defining distinct programmed cell death ligand-1 cut-offs. We analysed the diagnostic performance of all FDA/EMA-approved programmed cell death ligand-1 assays with emphasis on new restrictions for first-line treatment with atezolizumab and pembrolizumab. (Source: European Journal of Cancer)
Source: European Journal of Cancer - December 5, 2018 Category: Cancer & Oncology Authors: Markus Eckstein, Philipp Erben, Maximilian C. Kriegmair, Thomas S. Worst, Cleo-Aron Wei ß, Ralph M. Wirtz, Sven Wach, Robert Stoehr, Danijel Sikic, Carol I. Geppert, Veronika Weyerer, Simone Bertz, Johannes Breyer, Wolfgang Otto, Bastian Keck, Maximilian Tags: Original Research Source Type: research

Activity of axitinib in progressive advanced solitary fibrous tumour: Results from an exploratory, investigator-driven phase 2 clinical study
To explore the activity of axitinib in advanced solitary fibrous tumour (SFT). (Source: European Journal of Cancer)
Source: European Journal of Cancer - December 5, 2018 Category: Cancer & Oncology Authors: S. Stacchiotti, N. Simeone, S. Lo Vullo, C. Morosi, F.G. Greco, A. Gronchi, M. Barisella, P. Collini, N. Zaffaroni, G.P. Dagrada, A.M. Frezza, L. Mariani, P.G. Casali Tags: Original Research Source Type: research

Presence of antibodies to striated muscle and acetylcholine receptor in association with occurrence of myasthenia gravis with myositis and myocarditis in a patient with melanoma treated with an anti –programmed death 1 antibody
The increasing use of immune checkpoint inhibitors (ICIs) for the treatment of solid tumours increase the importance of management of immune-related adverse events (irAEs) [1]. Myasthenia gravis (MG) infrequently occurs in patients receiving ICIs [2 –6]. ICIs-related MG (iciMG) often shows concurrent elevation of the creatine kinase (CK) level, suggesting myositis and/or myocarditis, and results in higher frequencies of myasthenia crisis with a risk of death [4,5,7]. Anti-striated muscle antibodies (Str-Abs) may be useful biomarkers for iciMG with myositis and/or myocarditis because they appear in cases of idiop...
Source: European Journal of Cancer - December 5, 2018 Category: Cancer & Oncology Authors: T. Shirai, Y. Kiniwa, R. Sato, T. Sano, K. Nakamura, Y. Mikoshiba, N. Ohashi, Y. Sekijima, R. Okuyama Tags: Letter to the Editor Source Type: research

A systematic review of trial-level meta-analyses measuring the strength of association between surrogate end-points and overall survival in oncology
Surrogates are frequently used in cancer medicine as the end-point of clinical trials and as the basis of United States Food and Drug Administration  approvals, but they do not always represent outcomes that are important for patients. We aim to build upon previous umbrella reviews of surrogate validation studies by identifying and examining all meta-analyses of randomised controlled trials that evaluate the strength of correlation between over all survival (OS) and surrogate markers. (Source: European Journal of Cancer)
Source: European Journal of Cancer - December 5, 2018 Category: Cancer & Oncology Authors: Alyson Haslam, Spencer P. Hey, Jennifer Gill, Vinay Prasad Tags: Review Source Type: research

Association of clinical outcomes in metastatic breast cancer patients with circulating tumour cell and circulating cell-free DNA
Both circulating tumour cell (CTC) and total circulating cell-free DNA (ccfDNA) predict cancer patient prognosis. However, no study has explored the prognostic value of the combined use of CTC and ccfDNA. We aimed to investigate individual and joint effects of CTC and ccfDNA on clinical outcomes of metastatic breast cancer (MBC) patients. (Source: European Journal of Cancer)
Source: European Journal of Cancer - December 4, 2018 Category: Cancer & Oncology Authors: Zhong Ye, Chun Wang, Shaogui Wan, Zhaomei Mu, Zhenchao Zhang, Maysa M. Abu-Khalaf, Frederick M. Fellin, Daniel P. Silver, Manish Neupane, Rebecca J. Jaslow, Saveri Bhattacharya, Theodore N. Tsangaris, Inna Chervoneva, Adam Berger, Laura Austin, Juan P. Pa Tags: Original Research Source Type: research

Predictive biomarkers of response for immune checkpoint inhibitors in non –small-cell lung cancer
Immune checkpoint blockade has been a pivotal development in the management of advanced non –small-cell lung cancer (NSCLC). Although durable antitumour activity and improved survival have been observed in a subset of patients, there is a need for additional predictive biomarkers to improve patient selection and avoid toxicity in potential non-responders. This review will address the use and limitations of tumour programmed death-ligand 1 expression as a predictive biomarker and review emerging biomarker strategies specifically related to NSCLC including genetic alterations (tumour mutation burden, loss and gain acti...
Source: European Journal of Cancer - December 4, 2018 Category: Cancer & Oncology Authors: Arsela Prelaj, Rebecca Tay, Roberto Ferrara, Nathalie Chaput, Benjamin Besse, Raffaele Califano Tags: Review Source Type: research

Intense dose-dense epirubicin, paclitaxel, cyclophosphamide  versus weekly paclitaxel, liposomal doxorubicin (plus carboplatin in triple-negative breast cancer) for neoadjuvant treatment of high-risk early breast cancer (GeparOcto—GBG 84): A randomised phase III trial
GeparOcto compared efficacy and safety of two chemotherapy regimens in high-risk early breast cancer (BC): sequential treatment with intense dose-dense epirubicin, paclitaxel, and cyclophosphamide (iddEPC) and weekly treatment with paclitaxel plus non-pegylated liposomal doxorubicin (M, Myocet ®) with additional carboplatin (PM(Cb)) in triple-negative BC (TNBC). (Source: European Journal of Cancer)
Source: European Journal of Cancer - December 4, 2018 Category: Cancer & Oncology Authors: Andreas Schneeweiss, Volker M öbus, Hans Tesch, Claus Hanusch, Carsten Denkert, Kristina Lübbe, Jens Huober, Peter Klare, Sherko Kümmel, Michael Untch, Karin Kast, Christian Jackisch, Jörg Thomalla, Barbara Ingold-Heppner, Jens-Uwe Blohmer, Mahdi Reza Tags: Original Research Source Type: research