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Most anticancer molecules are administered in body-size-based dosing schedules, bringing up unsolved issues regarding pharmacokinetic data in heavy patients. The worldwide spread of obesity has not been matched by improved methods and strategies for tailored drug dosage in this population. The weight or body surface area (BSA)-based approaches may fail to fully reflect the complexity of the anthropometric features besides obesity in cancer patients suffering from sarcopenia. Likewise, there is a lack of pharmacokinetic data on obese patients for the majority of chemotherapeutic agents as well as for new target drugs and immunotherapy. Therefore, although the available findings point to the role of dose intensity in cancer treatment, and support full weight-based dosing, empirical dose capping often occurs in clinical practice in order to avoid toxicity. Thus a panel of experts of the Associazione Italiana Oncologia Medica (AIOM), Associazione Medici Diabetologi (AMD), Società Italiana Endocrinologia (SIE), and Società Italiana Farmacologia (SIF), provides here a consensus statement for appropriate cytotoxic chemotherapy and new biological cancer drug dosing in obese patients., Highlights • The worldwide spread of obesity is an emerging challenge also in cancer patients • Weight or BSA-based approaches do not adequately address the critical issue of optimal dosing for cancer drugs under obesity • Empirical dose capping is often employed in clinical practice to avoid toxicities among overweight and obese patients • There is a lack of clinical and pharmacokinetic studies in this population • Clinical practice recommendations should guide suitable dosing of cytotoxic and biological cancer drugs in obese patients

It is well recognised that adolescents and young adults (AYA) with cancer have inequitable access to oncology services that provide expert cancer care and consider their unique needs. Subsequently, survival gains in this patient population have improved only modestly compared with older adults and children with cancer. In 2015, the European Society for Medical Oncology (ESMO) and the European Society for Paediatric Oncology (SIOPE) established the joint Cancer in AYA Working Group in order to increase awareness among adult and paediatric oncology communities, enhance knowledge on specific issues in AYA and ultimately improve the standard of care for AYA with cancer across Europe. This manuscript reflects the position of this working group regarding current AYA cancer care, the challenges to be addressed and possible solutions. Key challenges include the lack of specific biological understanding of AYA cancers, the lack of access to specialised centres with age-appropriate multidisciplinary care and the lack of available clinical trials with novel therapeutics. Key recommendations include diversifying interprofessional cooperation in AYA care and specific measures to improve trial accrual, including centralising care where that is the best means to achieve trial accrual. This defines a common vision that can lead to improved outcomes for AYA with cancer in Europe.

Epithelioid hemangioendothelioma (EHE) is an ultra-rare, translocated, vascular sarcoma. EHE clinical behavior is variable, ranging from that of a low-grade malignancy to that of a high-grade sarcoma and it is marked by a high propensity for systemic involvement. No active systemic agents are currently approved specifically for EHE, which is typically refractory to the antitumor drugs used in sarcomas. The degree of uncertainty in selecting the most appropriate therapy for EHE patients and the lack of guidelines on the clinical management of the disease make the adoption of new treatments inconsistent across the world, resulting in suboptimal outcomes for many EHE patients. To address the shortcoming, a global consensus meeting was organized in December 2020 under the umbrella of the European Society for Medical Oncology (ESMO) involving >80 experts from several disciplines from Europe, North America and Asia, together with a patient representative from the EHE Group, a global, disease-specific patient advocacy group, and Sarcoma Patient EuroNet (SPAEN). The meeting was aimed at defining, by consensus, evidence-based best practices for the optimal approach to primary and metastatic EHE. The consensus achieved during that meeting is the subject of the present publication., Highlights • This consensus paper provides key recommendations on the management of epithelioid hemangioendothelioma (EHE). • Recommendations followed a consensus meeting between experts and a representative of the EHE advocacy group and SPAEN. • Authorship includes a multidisciplinary group of experts from different institutions from Europe, North America and Asia.

The coronavirus disease 2019 (COVID-19) pandemic has severely affected cancer care and research by disrupting the prevention and treatment paths as well as the preclinical, clinical, and translational research ecosystem. In Italy, this has been particularly significant given the severity of the pandemic's impact and the intrinsic vulnerabilities of the national health system. However, whilst detrimental, disruption can also be constructive and may stimulate innovation and progress. The Italian Association of Medical Oncology (AIOM) has recognized the impact of COVID-19 on cancer care continuum and research and proposes the '2021 Matera statement' which aims at providing pragmatic guidance for policymakers and health care institutions to mitigate the impact of the global health crisis on Italian oncology and design the recovery plan for the post-pandemic scenario. The interventions are addressed both to the pillars (prevention, diagnosis, treatment, follow-up, health care professionals) and foundations of cancer care (communication and care relationship, system organization, resources, research, networking). The priorities to be implemented can be summarized in the MATERA acronym: Multidisciplinarity; Access to cancer care; Telemedicine and Territoriality; Equity, ethics, education; Research and resources; Alliance between stakeholders and patients.

Patients with cancer are subjected to several imaging examinations which frequently require the administration of contrast medium (CM). However, it has been estimated that acute kidney injury (AKI) due to the injection of iodinated CM accounts for 11% of all cases of AKI, and it is reported in up to 2% of all computed tomography (CT) examinations. Remarkably, the risks of developing AKI are increased in the elderly, in patients with chronic kidney disease or diabetes, and with dehydration or administration of nephrotoxic chemotherapeutics. Given the common occurrence of post-contrast acute kidney injury (PC-AKI) in clinical practice, primary care physicians and all specialists involved in managing patients with cancer should be aware of the strategies to reduce the risk of this event. In 2018, a panel of five experts from the specialties of radiology, oncology and nephrology were speakers at the annual meeting of the Italian Society of Medical Radiology (Società Italiana di Radiologia Medica e Interventistica), with the aim of commenting on existing evidence and providing their experience on the incidence and management of PC-AKI in patients with cancer. The discussion represented the basis for this white paper, which is intended to be a practical guide organised by statements describing methods to reduce renal injury risks related to CM-enhanced CT examinations in patients with cancer.

The recent ESMO position paper on biosimilars in oncology1 was timely, given the rapidly increasing range of biologic medicines and the potential to develop biosimilar medicines in this area. As the position paper clearly states, biosimilar medicines can positively impact the financial sustainability of healthcare systems around the world.1 The paper also correctly highlights the importance of providing accurate information to all stakeholders involved. This is essential in order to avoid misunderstanding and misconceptions about biosimilar medicines. Biologic medicines, whether reference biologics or biosimilars, are recognised as being much more complex than traditional, chemically-synthesised drugs. A biosimilar, as defined by the EMA, is a biologic medicine that is similar to another biologic medicine that has already been authorised for use.2 A science-based regulatory framework has been established in the European Union (EU) since 2005 to ensure the development and approval of high-quality biosimilars; this framework is regularly reviewed and updated.3–5 The requirements for biosimilar development and approval are based on those that are in place for any biologic medicine; the manufacturer is required to demonstrate similarity to the reference medicine in terms of safety, efficacy and quality. This contrasts with the requirements for approval of generic versions of chemically synthesised, small-molecule drugs, which typically only require demonstration of identical structure and pharmacological …

We welcome the position paper by the European Society for Medical Oncology on issues surrounding biosimilars.1 After recent approval of the first biosimilars of monoclonal antibodies (mAbs) in oncology, the input of medical oncology societies to an open discussion of medical opinion and provision of guidance regarding the introduction of these drugs into clinical practice are urgently needed. As pointed out by Tabernero et al , safety and efficacy of biosimilars are the shared responsibility of manufacturers and regulatory bodies. We agree that a robust regulatory framework for authorisation of biosimilars is in place in Europe, and properly developed and approved biosimilars can be considered a valid treatment option.2 In line with the authors and the whole pharmaceutical industry,3 we advocate that …

Background The Surveillance of Rare Cancers in Europe (RARECARE) project proposed a definition and a list of rare cancers. The Joint Action on Rare Cancers (JARC), launched by the European Union and involving 18 member states and 34 partners, promoted a wide consensus effort to review the list. Patients and methods A group of experts was set up, including scientific societies, member state representatives of JARC, representatives of the European Reference Networks dedicated to rare cancers and rare cancer patient advocates. The definition and the list of rare clinical entities, based on the incidence data provided by two European projects (RARECARE and RARECAREnet), were rediscussed through a consensus meeting of the expert panel. Results By consensus, it was reiterated that the best criterion for a definition of rare cancers is incidence, rather than prevalence. By consensus, the experts slightly modified the composition of the tiers of rare cancers, according to the definition based on an incidence threshold

In oncology, as in other clinical fields, different treatments are often approved for the same therapeutic indication. In many cases, no direct comparisons are available to inform the choice in clinical practice. In 2015, the Italian Association of Medical Oncology (AIOM) instructed a working group, including both clinicians and methodologists, to discuss the issue of the best choice among different treatments available for the same indication. The working group discussed 3 different scenarios: (1) biosimilar drugs; (2) different drugs with same mechanism of action; (3) different drugs with different mechanism of action. For each scenario, methodological issues were discussed, along with the priority for investment of resources in the conduct of clinical trials testing direct comparison. As for biosimilar drugs, the panel recommended that, following comparability exercise and approval by regulatory agencies, they should be widely used, considered that their use allows financial savings. As for different drugs (with either the same or a different mechanism of action), the panel agreed that indirect comparisons and network meta-analyses are associated with relevant risk of bias and imprecision, and direct comparisons should be encouraged. The priority of these direct comparisons should be higher when the potential differences in efficacy and/or toxicity are clinically relevant. The choice of the study design (superiority vs non-inferiority) depends on the toxicity profiles and also on the presumed difference in efficacy. Scientific societies should put pressure on public bodies to identify all the administrative and financial mechanisms useful to facilitate the conduct of trials testing direct comparisons, when needed. Decision about therapeutic equivalence can have important consequences on innovation: the availability of drugs characterised by the same effectiveness, but at a lower cost, could enable non-negligible savings of economic resources that could be used to guarantee access to innovative, high-cost drugs.

International audience

Early in 2017, The European Society for Medical Oncology (ESMO) published a position paper on biosimilars for oncology prescribers.1 Since then, both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have approved biosimilar versions of monoclonal antibodies (mAbs) used for the treatment of several cancer types (eg, rituximab in Europe, bevacizumab and trastuzumab in the USA).2 3 The ESMO position paper was rightly welcomed as a timely addition to the discussion around this important topic.4 The position paper correctly highlighted the importance of accurate information about biosimilars if misconceptions and misunderstanding are to be avoided among oncologists and other stakeholders.1 It is encouraging that ESMO has continued on this mission to provide information and education; special sessions on biosimilars were incorporated into the main programmes for both the ESMO and ESMO Asia congresses in 2017, and the organisation has been represented at several other important meetings (including the 15th Biosimilar Medicines Conference). They also launched a survey on awareness of biosimilars among oncologists in 2017, the results of which are eagerly awaited. Extrapolation is arguably the part of the biosimilar concept that is most commonly misunderstood. It is defined as the authorisation of a biosimilar medicine for clinical indications of the reference …

Myelodysplastic syndrome (MDS) is a disease of elderly with a median age of 70.1 Azacitidine is approved for high-risk MDS, chronic myelomonocytic leukaemia (CMML) and acute myeloid leukaemia (AML) with less than 30% blasts.2 Treatment with azacitidine has shown reduced transfusion requirement, improved leukaemia-free and overall survival.2 3 However, many elderly patients may find it difficult to attend day case 7 days a month until progression and further additional attendances for blood tests, clinics and transfusions. We recognised that the requirement for patients to make multiple hospital visits for chemotherapy treatment was having an increasingly negative impact on their quality of life and that of their relatives/carers. This also resulted in patients declining accessible treatment for their disease. Community chemotherapy service was set up with a view to improve the outcome and quality of care by taking treatment closer to home. National Health Service white paper in 2010 focused on extending choice for patients and moving cancer services away from major cancer centres when feasible. Key driver for community chemotherapy is improved patient choice and experience.4 5 In this article, we explain our community chemotherapy initiative project and our experiences so far. ### Aim The initial aim of the service was to reduce the number of visits required by patients to hospital, giving greater choice in the delivery of their treatment and therefore reducing the impact of their disease on their daily lives. The service was also aimed to increase efficiency in the delivery of chemotherapy by the Trust. These continued to be the overarching aims of the service to ultimately improve the experience of our patients and efficiency of the service. ### Project details All suitable patients who are under the care of a Heart of England Foundation Trust (HEFT) haematology consultants receiving treatment with subcutaneous chemotherapy within the Birmingham …

Together with surgery and radiotherapy, systemic treatment with cytotoxic chemotherapy and molecular targeted agents is one of the main therapeutic pillars in the treatment of soft-tissue sarcomas and is the mainstay of treatment in patients with advanced or metastatic disease. Unlike other more common malignancies such as breast and colorectal cancer, the role of chemotherapy when used in the adjuvant setting in soft-tissue sarcomas is less well defined. Results from prior studies have been conflicting, in part due to the heterogeneity and rarity of the disease, and large-scale meta-analysis has been performed to address this issue. Neoadjuvant chemotherapy, defined as the use of chemotherapy before definitive treatment with surgery or radiotherapy, has distinct theoretical and practical advantages, which can potentially be beneficial to the patient. However, the currently available evidence to support its use is even more scarce. In this review article, we describe the current established data behind the use of adjuvant chemotherapy in selected patients with localised soft-tissue sarcomas and, through extrapolation of available data, discuss the potential role of it when used in the upfront setting.

Comprehensive molecular characterisation of muscle-invasive urothelial carcinoma and variant histological subtypes has led to the identification of recurrent driver mutations that are distinct in these aggressive subgroups of bladder cancer. While distant metastasis dominates as a pattern of relapse following radical cystectomy or chemoradiotherapy, loco-regional control rates are also suboptimal with single modality local treatment, and likewise, harbour equivocal implications on the long-term prognosis of patients. The role of adjuvant radiotherapy for optimising disease control within the pelvis is controversial, with limited evidence to support its efficacy. Herein, we present a stepwise review on adjuvant radiotherapy post-cystectomy; first, discussing the evidence to date supporting the concept that adjuvant radiotherapy is effective in targeting occult metastases within the pelvis, and adds to the benefits of adjuvant chemotherapy. Next, we outlined the principles underlying the definition of radiotherapy target volumes. To conclude, we addressed the need for appropriate patient stratification for treatment intensification, based on existing clinical models and novel molecular indices of aggression in muscle-invasive urothelial cancers and variant histological subtypes.

Objective Nivolumab is a fully human IgG4 programmed cell death 1 immune checkpoint inhibitor monoclonal antibody approved for the treatment of non-small cell lung cancer (NSCLC). The aim of this study was to evaluate the safety and efficacy of nivolumab in Japanese patients with advanced or recurrent non-squamous NSCLC. Methods In this multicentre phase II study, patients with advanced or recurrent non-squamous NSCLC, which had progressed after platinum-containing chemotherapy, were treated with nivolumab 3 mg/kg, intravenously every 2 weeks until progressive disease or unacceptable toxicity was observed. The primary end point was independent radiology review committee (IRC) assessed overall response rate (ORR) and the secondary endpoints included ORR (investigator assessed), progression-free survival (PFS), overall survival (OS), duration of response, time to response, best overall response, and safety. Results 76 patients were enrolled across 19 sites in Japan. The ORR (IRC assessed) was 22.4% (95% CI 14.5% to 32.9%). The median PFS and OS were 2.8 months (95% CI 1.4 to 3.4) and 17.1 months (95% CI 13.3 to 23.0), respectively. The OS rate at 1 year was 68.0% (95% CI 56.2% to 77.3%). Current/former smokers were more responsive to treatment than non-smokers (ORR 29.1% vs 4.8%). Patients with epidermal growth factor receptor (EGFR) mutation wild type/unknown showed higher ORR compared with EGFR mutation-positive patients (ORR 28.6% vs 5.0%) and programmed cell death ligand-1 (PD-L1) expression was likely associated with higher ORR, longer PFS and OS. Treatment-related adverse events of grade 3 or higher were reported in 17 patients; these events resolved or were resolving with appropriate treatment including steroid therapy or discontinuation of nivolumab. Conclusions Nivolumab was well tolerated and showed clinical efficacy in Japanese patients with non-squamous NSCLC progressed after platinum-containing chemotherapy, especially in those with a history of smoking, wild type/unknown EGFR mutation status or positive PD-L1 expression. Trial registration number JapicCTI-132073.

Background The European Society for Medical Oncology (ESMO) 2021 conference provided a high number of randomized phase III trial reports, many of which were claimed to be practice changing. Given the short time available for conference presentations, results and conclusions tend to have greatest priority with less time remaining for study background and study methodology. Purpose On behalf of the ESMO Practicing Oncologists Working Group, 11 potentially practice-changing reports were selected and screened for three main questions: (i) Did the investigators provide sufficient details with regard to Patients and Methods to make the results comprehensible? (ii) Were there any reasons to consider bias? (iii) To which extent did the results presented translate to clinical benefit? Results In 2 out of 11 trials, the study design presented differed considerably from the study design described at ClinicalTrials.gov. Allocation concealment was not carried out in 6 out of 11 trials. In none of the trials reporting progression-free survival was informative censoring considered an issue. In none of the trials reporting overall survival was desirable crossover considered an issue. Defined trial outcome measures depicted at ClinicalTrials.gov, which could boost or weaken the ESMO-Magnitude of Clinical Benefit Scale score, were often lacking in the presentation. Study success was claimed in a heterogeneous manner, which was often not clearly linked to overall clinical benefit. Conclusion ESMO conference presentations can inform the scientific community and catalyze further research but cannot replace the full papers in peer-reviewed journals, which are needed to estimate the thoroughness of the results, the overall impact on clinical benefit and the consequences for future treatment guidelines., Highlights • An oncological peer-reviewed paper is lengthy and well structured. • An oncological conference presentation is short and less structured, but its impact can be high. • ESMO 2021 conference encompassed many possibly practice-shaping phase III trial reports. • A survey of 11 selected reports to ascertain if the conclusions made were adequately underlined by the provided information.

Background Licensed systemic treatment options for platinum-sensitive recurrent ovarian cancer are platinum-based chemotherapy and maintenance treatment with bevacizumab and poly (ADP-ribose) polymerase inhibitors. For platinum-resistant disease, several non-platinum options are available. We aimed to assess the clinical benefit of these treatments according to the European Society of Medical Oncology (ESMO)-Magnitude of Clinical Benefit Scale (MCBS). Materials and methods A PubMed search was carried out including all studies evaluating systemic treatment of recurrent epithelial ovarian cancer, from 1990 onwards. Randomised trials with an adequate comparator and design showing a statistically significant benefit of the study arm were independently scored by two blinded observers using the ESMO-MCBS. Results A total of 1127 papers were identified, out of which 61 reported results of randomised trials of sufficient quality. Nineteen trials showed statistically significant results and the studied treatments were graded according to ESMO-MCBS. Only three treatments showed substantial benefit (score of 4 on a scale of 1-5) according to the ESMO-MCBS: platinum-based chemotherapy with paclitaxel in the platinum-sensitive setting and the addition of bevacizumab to chemotherapy in the platinum-resistant setting. The WEE1 inhibitor adavosertib (not licensed) also scores a 4, based on a recent small phase II study. Assessment of quality-of-life data and toxicity using the ESMO-MCBS showed to be complex, which should be taken into account in using this score for clinical decision making. Conclusion Only a few licensed systemic therapies for recurrent ovarian cancer show substantial clinical benefit based on ESMO-MCBS scores. Trials demonstrating overall survival benefit are sparse., Highlights • Benefit of systemic treatments for recurrent ovarian cancer was scored on the ESMO-MCBS. • From 1127 identified papers, only 3 trials out of 19 that were suitable for grading showed substantial clinical benefit. • Trials demonstrating overall survival benefit are sparse.

Cancer care has been profoundly impacted by the global pandemic of severe acute respiratory syndrome coronavirus 2 disease (coronavirus disease 2019, COVID-19), resulting in unprecedented challenges. Supportive care is an essential component of cancer treatment, seeking to prevent and manage chemotherapy complications such as febrile neutropenia, anaemia, thrombocytopenia/bleeding, thromboembolic events and nausea/vomiting, all of which are common causes of hospitalisation. These adverse events are an essential consideration under routine patient management, but particularly so during a pandemic, a setting in which clinicians aim to minimise patients' risk of infection and need for hospital visits. Professional medical oncology societies have been providing updated guidelines to support health care professionals with the management, treatment and supportive care needs of their patients with cancer under the threat of COVID-19. This paper aims to review the recommendations made by the most prominent medical oncology societies for devising and modifying supportive care strategies during the pandemic., Highlights • Cancer care has been profoundly impacted by the global pandemic of COVID-19, resulting in unprecedented challenges. • Oncology societies have updated guidelines for the supportive care needs of patients with cancer under the threat of COVID-19. • This paper reviews recommendations from prominent oncology societies for providing supportive care during the pandemic.

Within the 3 years of its existence, ESMO Open – Cancer Horizons has so far published a total of 330 articles dealing with all possible aspects of cancer and cancer care. These have included papers in the following areas: epidemiological studies1 2; access to cancer care3–7; the advent of biologicals and their broad use in the clinic8 9; various aspects of magnitude of clinical benefit achieved by the use of certain drugs10 11; biological considerations on the regulation of tumour growth12 13 and propagation14–16; clinical cutting-edge papers on the treatment of cancer in selected unfamiliar situations1 17–21; …

ESMO Open was launched in January 2016. Since its launch, there have been 199 submissions which have reached a final decision. Due to this impressive acceptance within the community of oncologists, ESMO Open was listed in PubMedCentral within a remarkably short time after the appearance of the first paper (less than 10 months). Apart from important reviews of clinical relevance, many original papers were submitted out of which 15—corresponding to 9% of all publications—were coming …

Despite the efficacy of a number of first-line treatments, most patients with advanced-stage non-small cell lung cancer (NSCLC) experience disease progression that warrants further treatment. In this review, we examine the role of novel active agents for patients who progress after first-line therapy and who are not candidates for targeted therapies. More therapeutic options are needed for the management of patients with NSCLC after failure of first-line chemotherapy. A PubMed search was performed for articles from January 2012 to May 2015 using the keywords NSCLC, antiangiogenic, immunotherapy, second-line, novel therapies and English language articles only. Relevant papers were reviewed; papers outside that period were considered on a case-by-case basis. A search of oncology congresses was performed to identify relevant abstracts over this period. In recent years, antiangiogenic agents and immune checkpoint inhibitors have been added to our armamentarium to treat patients with advanced NSCLC who have progressed on first-line chemotherapy. These include nintedanib, a triple angiokinase inhibitor; ramucirumab, a vascular endothelial growth factor receptor-2 antibody; and nivolumab, pembrolizumab and atezolizumab, just three of a growing list of antibodies targeting the programmed death receptor-1 (PD-1)/PD ligand-1 pathway. Predictive and prognostic factors in NSCLC treatment will help to optimise treatment with these novel agents. The approval of new treatments for patients with NSCLC after the failure of first-line chemotherapy has increased options after a decade of few advances, and holds promise for future evolution of the management of NSCLC.

BACKGROUND: The use of immune checkpoint inhibitors (ICIs) in the front-line treatment of advanced non-small-cell lung cancer (NSCLC) is currently the standard of care. However, as clinical trials include a very limited number of elderly patients, evidence on the safety and efficacy of using ICI-based regimens is still limited. METHODS: A virtual International Expert Panel took place in July 2022 to review the available evidence on the use of ICI-based regimens in the first-line setting in elderly patients with NSCLC and provide a position paper on the field both in clinical practice and in a research setting. RESULTS: All panelists agreed that age per se is not a limitation for ICI treatments, as the elderly should be considered only as a surrogate for other clinical factors of frailty. Overall, ICI efficacy in the elderly population is supported by reviewed data. In addition, the panelists were confident that available data support the safety of single-agent immunotherapy in elderly patients with NSCLC. Conversely, concerns were expressed on the safety of chemo + ICI-based combination, which were considered mainly related to the toxicities of chemotherapy components. Therefore, suggestions were proposed to tailor combined approaches in the elderly patients with NSCLC. The panelists defined high, medium, and low priorities in clinical research. High priority was attributed to implementing the real-world assessment of elderly patients treated with ICIs, who are mostly underrepresented in pivotal clinical trials. CONCLUSIONS: Based on the current evidence, the panelists outlined the significant limitations affecting the clinical practice in elderly patients affected by NSCLC, and reached common considerations on the feasibility, safety, and effectiveness of ICI monotherapy and ICI combinations in the first-line setting.

Subgroup analyses of randomized controlled trials are very common in oncology; nevertheless, the methodological approach has not been systematically evaluated. The present analysis was conducted with the aim of describing the prevalence and methodological characteristics of the subgroup analyses in randomized controlled trials in patients with advanced cancer.A systematic literature search using PubMed was carried out to identify all phase III randomized controlled trials conducted in adult patients affected by locally advanced or metastatic solid tumours, published between 2017 and 2020.Overall, 253 publications were identified. Subgroup analyses were reported in 217 (86%) publications. A statistically significant association of presence of subgroup analysis with study sponsor was observed: subgroup analyses were reported in 157 (94%) for-profit trials compared with 60 (70%) non-profit trials (P0.001). Description of the methodology of subgroup analysis was completely lacking in 82 trials (38%), only cited without methodological details in 100 trials (46%) and fully described in 35 trials (16%). Forest plot of subgroup analyses for the primary endpoint was available in 195 publications (77%). Among publications with reported forest plots, the median number of subgroups for primary endpoint was 19 (range 6-78). Out of the 217 publications with subgroup analyses, authors discuss the heterogeneity of treatment effect among different subgroups in 173 publications (80%), although a formal test for interaction for subgroup analysis of primary endpoint was reported for at least one variable only in 60 publications (28%). Correction for multiplicity was explicitly carried out only in nine trials (4%).The very high prevalence of subgroup analyses in published papers, together with their methodological weaknesses, makes advisable an adequate education about their correct presentation and correct reading. More attention about proper planning and conduction of subgroup analysis should be paid not only by readers, but also by authors, journal editors and reviewers.

BACKGROUND: Liquid biopsy (LB) is a rapidly evolving diagnostic tool for precision oncology that has recently found its way into routine practice as an adjunct to tissue biopsy (TB). The concept of LB refers to any tumor-derived material, such as circulating tumor DNA (ctDNA) or circulating tumor cells that are detectable in blood. An LB is not limited to the blood and may include other fluids such as cerebrospinal fluid, pleural effusion, and urine, among others. PATIENTS AND METHODS: The objective of this paper, devised by international experts from various disciplines, is to review current challenges as well as state-of-the-art applications of ctDNA mutation testing in metastatic non-small-cell lung cancer (NSCLC). We consider pragmatic scenarios for the use of ctDNA from blood plasma to identify actionable targets for therapy selection in NSCLCs. RESULTS: Clinical scenarios where ctDNA mutation testing may be implemented in clinical practice include complementary tissue and LB testing to provide the full picture of patients' actual predictive profiles to identify resistance mechanism (i.e. secondary mutations), and ctDNA mutation testing to assist when a patient has a discordant clinical history and is suspected of showing intertumor or intratumor heterogeneity. ctDNA mutation testing may provide interesting insights into possible targets that may have been missed on the TB. Complementary ctDNA LB testing also provides an option if the tumor location is hard to biopsy or if an insufficient sample was taken. These clinical use cases highlight practical scenarios where ctDNA LB may be considered as a complementary tool to TB analysis. CONCLUSIONS: Proper implementation of ctDNA LB testing in routine clinical practice is envisioned in the near future. As the clinical evidence of utility expands, the use of LB alongside tissue sample analysis may occur in the patient cases detailed here.

Non-small-cell lung cancer (NSCLC) harbouring HER2 alterations is now considered a distinct molecular subtype. The activation of HER2 in NSCLC occurs via three mechanisms, i.e. gene mutation (1%-4% of cases), gene amplification (2%-5%) and protein overexpression (2%-30%), with different prognostic and predictive outcomes. So far, non-selective tyrosine kinase inhibitors (TKIs) have shown a minor benefit in HER2-mutant NSCLC patients with objective response rates (ORRs) ranging from 0% to 19%. Trastuzumab-based chemotherapy was not found to be superior to chemotherapy alone [median progression-free survival (PFS) 6.1 versus 7 months, respectively] and dual HER2 antibody blockade with trastuzumab and pertuzumab had limited efficacy (ORR 13%-21%). In contrast, novel more selective HER2 TKIs such as poziotinib and pyrotinib have shown a promising activity in HER2-mutant pre-treated NSCLC patients, with response rates up to 38% and 44%, respectively. The most encouraging data come from phase II studies that evaluated the antibody–drug conjugates (ADCs) ado-trastuzumab–emtansine and trastuzumab–deruxtecan in patients with HER2-mutant NSCLC, with response rates of 50% and 62%, respectively. These agents are bringing hope to the management of HER2-altered NSCLC. Moreover, a paradigm shift from monotherapies towards combinations of agents with distinct mechanisms of action, such as ADCs with irreversible TKIs or immune checkpoint inhibitors, is already taking place and will change the therapeutic landscape of HER2-driven NSCLC. This paper provides a practical, concise and updated review on the therapeutic strategies in NSCLC with HER2 molecular alterations., Highlights • Activation of Her2 in NSCLC occurs via gene mutation, amplification or protein overexpression. • Selective Her2 TKIs like poziotinib and pyrotinib induced responses in up to 44% of pre-treated Her2-mutant NSCLC patients. • ADCs trastuzumab–emtansine and trastuzumab–deruxtecan showed impressive response rates in 62% of Her2-mutant NSCLC patients. • Ongoing studies evaluating combination strategies may help improve the therapeutic landscape in Her2-dependent NSCLC.

Cutaneous melanoma is the most lethal form of skin cancer and its incidence has been increasing in the past 30 years. Although this is completely resectable in most cases, thicker melanoma and those with regional lymph-node involvement are at a high risk of relapse. In recent years, the management of locoregional disease has drastically changed. In particular, in the 8th Edition of the American Joint Committee on Cancer (AJCC), subgroup classification of TNM (tumor–node–metastasis) has been modified, with the addition of the IIID stage. Furthermore, in recent randomized trials, completion lymph node dissection in case of sentinel lymph node biopsy positivity has not been shown to offer any improvement in overall survival versus observation. Consequently, radical dissection has been recommended as the standard treatment, but only in patients with palpable nodal metastases. However, the major novelty in the treatment of locally advanced melanoma has been the introduction of drugs, already used for metastatic disease, that have also shown clinical efficacy in the adjuvant setting. In fact, immunotherapies and, in the case of BRAF V600E/K-mutated melanoma, combination treatment of BRAF and MEK inhibitors have improved recurrence-free survival in these patients. In this paper, we will describe the current management of a patient with radically resectable melanoma and discuss the key points in light of the latest scientific evidence.

The therapeutic landscape in the treatment of advanced/metastatic renal cell cancer has evolved over the last 2 years with the advent of immune checkpoint inhibitors. In 2018 and 2019, marketing authorisations valid throughout the European Union were issued for nivolumab and ipilimumab dual checkpoint inhibition and pembrolizumab or avelumab in combination with the tyrosine kinase inhibitor axitinib. These applications presented numerous regulatory challenges. In this paper, we summarise the main regulatory considerations, originating from the assessment of the dossiers submitted from the applicants for the three combinations. The regulatory issues are grouped in four sections: clinical pharmacology, efficacy, biomarkers and safety. In each section, we describe the issues raised during the regulatory evaluation performed by the Committee for Medicinal Products for Human Use (CHMP) assessors. The CHMP assessments determine whether the medicines concerned meet the necessary quality, safety and efficacy requirements, and whether the benefit–risk balance is positive. In summary, although the overall benefit–risk was considered positive for the three combinations, the immaturity of the outcome data and the absence of long-term safety data remain issues to be addressed. Postauthorisation efficacy studies have been required to confirm the effects of the new combinations.

© © Author (s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ on behalf of the European Society for Medical Oncology. Breathlessness is among the most common and deteriorating symptoms in patients with advanced cancer, which may worsen towards the end of life. Breathlessness in patients with estimated life expectancy of weeks to days has unique clinical features: it tends to worsen rapidly over days to hours as death approaches often despite current symptom control measures. Breathlessness in patients during the last weeks to days of life can be called € terminal breathlessness'. While evidence has accumulated for the management of breathlessness in patients with cancer who are not dying, such evidence may not be fully applied to terminal breathlessness. Only a few studies have investigated the best practice of terminal breathlessness in patients with cancer. In this paper, we summarise the current evidence for the management of terminal breathlessness, and propose future directions of clinical research.

Introduction Predatory journals harm the integrity of science as principles of ‘good scientific practice’ are bypassed by omitting a proper peer-review process. Therefore, we aimed to explore the awareness of predatory journals among oncologists. Methods An online survey among oncologists working in Germany or Austria of various professional surroundings was conducted between October 2018 and April 2019. Results One hundred and eighty-eight participants (55 women (29.2%), 128 men (68.1%)) completed the questionnaire. 41 (21.8%) participants indicated to work in a hospital, 24 (12.8%) in private practice and 112 (59.6%) in a university hospital. 98.9% of participants indicated to actively read scientific articles and consider them in clinical decision-making (96.3%). 90.4% of participants indicated to have scientific experience by publishing papers in journals with peer-review system. The open-access system was known by 170 (90.4%), predatory journals by 131 (69.7%) and Beall’s list by 52 participants (27.7%). Predatory journals were more likely to be known by participants with a higher number of publications (p

Background A skilled health workforce is instrumental for the delivery of multidisciplinary cancer care and in turn a critical component of the health systems. There is, however, a paucity of data on the vast inequalities in cancer workforce distribution, globally. The aim of this study is to describe the global distribution and density of the health care workforce involved in multidisciplinary cancer management. Methods We carried out a systematic review of the literature to determine ratios of health workers in each occupation involved in cancer care per 100 000 population and per 100 cancer patients (PROSPERO: protocol CRD42018095414). Results We identified 33 eligible papers; a majority were cross-sectional surveys (n = 16). The analysis of the ratios of health providers per population and per patients revealed deep gaps across the income areas, with gradients of workforce density, highest in high-income countries versus low-income areas. Benchmark estimates of optimal workforce availability were provided in a secondary research analysis: mainly high-income countries reported workforce capacities closer to benchmark estimates. A paucity of literature was defined for critical health providers, including for pediatric oncology, surgical oncology, and cancer nurses. Conclusion The availability and distribution of the cancer workforce is heterogeneous, and wide gaps are described worldwide. This is the first systematic review on this topic. These results can inform policy formulation and modelling for capacity building and scaleup., Highlights • Workforce is an essential component of the health systems. • Stark inequalities are reported for the distribution of health workforce worldwide, but data are limited. • We aimed at portraying the first global figure of the comprehensive cancer workforce for cancer management. • Inequalities in density and distribution of the workforce regard all the key health personnel involved in cancer management. • These data will inform the development of evidence-informed policies for the workforce in low- and middle-income countries.

Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent and increasing liver disease, which encompasses a variety of liver diseases of different severity. NAFLD can lead to liver cirrhosis with all its complications as well as hepatocellular carcinoma (HCC). Steatosis of the liver is not only related to obesity and other metabolic risk factors, but can also be caused by several drugs, including certain cytotoxic chemotherapeutic agents. In patients undergoing liver surgery, hepatic steatosis is associated with an increased risk of post-operative morbidity and mortality. This review paper summarizes implications of hepatic steatosis on the management of patients with cancer. Specifically, we discuss the epidemiological trends, pathophysiological mechanisms, and management of NAFLD, and its role as a leading cause of liver cancer. We elaborate on factors promoting immunosuppression in patients with NAFLD-related HCC and how this may affect the efficacy of immunotherapy. We also summarize the mechanisms and clinical course of chemotherapy-induced acute steatohepatitis (CASH) and its implications on cancer treatment, especially in patients undergoing liver resection., Highlights • Non-alcoholic fatty liver disease can lead to cirrhosis with all its complications, including hepatocellular carcinoma. • Chemotherapy-associated acute steatohepatitis is a side-effect of chemotherapeutic agents and may limit treatment options. • In this review we summarize current clinical concepts of NAFLD and CASH that help clinicians in their clinical practice.

On 18 September 2017, a marketing authorisation valid through the European Union (EU) was issued for midostaurin in combination with standard daunorubicin and cytarabine induction and high-dose cytarabine consolidation chemotherapy and for patients in complete response followed by midostaurin single agent maintenance therapy, for adult patients with newly diagnosed acute myeloid leukaemia (AML) who are Fms-like tyrosine kinase 3 mutation positive and as monotherapy for the treatment of adult patients with aggressive systemic mastocytosis (ASM), systemic mastocytosis with associated haematological neoplasm (SM-AHN) or mast cell leukaemia (MCL). The recommended dose of midostaurin is 50 mg orally twice daily for AML and 100 mg orally twice daily for ASM, SM-AHN and MCL. Midostaurin was evaluated in two pivotal studies. Study A2301 (RATIFY) included 717 patients with AML. Overall survival (OS) was statistically significantly different between the two groups, and the median OS was 74.7 months in the midostaurin+daunorubicin+cytarabine group and 25.6 months in the placebo+daunorubicin+cytarabine group (HR 0.774; 95% CI 0.629 to 0.953; p=0.0078). Study D2201 included 116 patients with ASM, SM-AHN or MCL. An overall response rate, by IWG-MRT/ECNM (international working group – myelofibrosis research and treatment/European competence network on mastocytosis) criteria of 28.3% was observed in all patients and 60.0%, 20.8% and 33.3% in patients with ASM, SM-AHN and MCL respectively. The most common adverse drug reactions (ADRs) with midostaurin treatment in AML were febrile neutropenia, nausea, exfoliative dermatitis, vomiting, headache, petechiae and fever. In ASM, SM-AHN, MCL the most common ADRs were nausea, vomiting, diarrhoea, peripheral oedema and fatigue. The objective of this paper is to summarise the scientific review of the application leading to regulatory approval in the EU.

Background Corresponding with improved survival among patients with breast cancer, the awareness of the long-term effects of cancer treatments has increased. CANcer TOxicities (CANTO) aims to identify predictors of development and persistence of long-term toxicities in patients treated for stages I–III breast cancer and to characterise their incidence, as well their impact. In this paper, we describe the methodology used in this study and provide a first characterisation of the study population.Methods CANTO (NCT01993498) is a French prospective, longitudinal cohort study enrolling patients with invasive cT0-cT3cN0-3M0 breast cancer of 26 French cancer centres. Patients are assessed at diagnosis, 3–6 (M0), 12 (M12), 36 (M36) and 60 (M60) months after completion of primary surgery, chemotherapy or radiotherapy whichever comes last. CANTO collects clinical, treatment, toxicity data, an extensive list of validated patient-reported outcomes (focusing on quality of life, psychological and behavioural questionnaires) and ad hoc socioeconomic questionnaires. Blood collection is performed at diagnosis, M0, M12, M36 and M60. Biologic sub-studies are ongoing (eg, microbiotic and cognitive sub-study).Results Enrolment started in 2012; by October 2018, 12 012 patients had been enrolled. Data collected have a low missing completion rate (

Nine per cent of patients with metastatic cancer harbour genomic alterations that are recognised as biomarkers for optimal treatment selection in current standard of care. An additional 27% carries genomic aberrations for which compelling clinical evidence exists supporting the use of these alterations as predictive biomarkers for drug response outside the registered indication.1 As novel molecular and genomic treatment indications are explored in rapid pace, the generation and correct interpretation of molecular tumour profiles are quickly becoming a necessity for offering optimal cancer treatment. The complexity and vast amounts of data generated through molecular profiling techniques, like next-generation sequencing, make expert review an absolute requirement in order to translate molecular profiles into clinical benefit for our patients. Leading cancer care providers are currently trying to address this by developing the so called ‘molecular tumour boards’ (MTBs), which comprise experts of various disciplines who help clinicians to interpret the molecular profiles of their patients. This is a challenging task and many uncertainties about the optimal implementation of these boards remain. Among different institutions, implementations can differ on various grounds: technically (eg, the used sequencing techniques, bioinformatics pipelines), composition wise (eg, which types of specialists are involved) or organisationally (eg, centralised vs localised). Recently, Moore and colleagues share how they implemented an MTB in the UK: the Sarah Cannon Research Institute (SRCI) UK/UCL Genomics Review Board (GRB). The paper describes the molecular profiling results, given recommendations and clinical trial enrolment of 895 patients reviewed by the GRB. In addition to these prospective data, the authors share the challenges encountered during the establishment of the GRB. A multidisciplinary team comprising physicians, a molecular oncologist, …

Biosimilars; Oncologia; Prescriptors Biosimilares; Oncología; Prescriptores Biosimilars; Oncology; Prescribers Background: Biosimilars can potentially improve the sustainability of cancer care; however, uptake is sometimes limited by safety concerns and a lack of understanding of the concept of extrapolation. The European Society for Medical Oncology (ESMO) conducted a survey to assess the current level of knowledge, understanding and comfort of use of biosimilars among prescribers specialised in oncology. Methods: A 19-question survey was developed using the SurveyMonkey online platform (https://www.surveymonkey.com/). Data collection occurred between September and October 2017 and included paper and online responses. Results: Overall, 393 responses were received from prescribers. Overall, 49.0% of prescribers use biosimilars in clinical practice and most (79.2%) rate their general knowledge of biosimilars as average to very high. Potential increased risk of immunogenicity remains a significant concern of switching. Gaps in knowledge identified by the survey include biosimilar development, clinical trial design and endpoint selection, and requirements for extrapolation, which should form the focus of future educational initiatives. A substantial demand remains for further educational activities with equal preference for online and face-to-face initiatives. A higher rate of biosimilar use (56.3% vs 46.5%), knowledge of biosimilar development and trial design, and comfort with extrapolation, but a lower knowledge of European Medicines Agency definitions, was found among prescribers from Asia-Pacific versus those from Europe. Conclusion: Encouraging levels of prescriber use and general knowledge of biosimilars were found, but a substantial need for further education remains. Efforts should be made worldwide to align terms, definitions and guidelines for the development and approval of biosimilars.

Although lung cancer remains the leading cause of death from cancer worldwide, the advent of immunotherapy is changing the survival of patients affected by non-small cell lung cancer (NSCLC). A multitude of clinical trials are evaluating different immune checkpoints inhibitors in this new field of thoracic oncology. At the beginning of the immunotherapy era, nivolumab, pembrolizumab and atezolizumab showed high efficacy in patients with advanced NSCLC in second-line setting, receiving approvals for clinical practice. Nivolumab and atezolizumab are approved independently from programmed death lig and 1 (PD-L1) expression, while pembrolizumab is currently approved only for patients with PD-L1 expression ≥1%. The role of PD-L1 expression acquired more interest considering first-line clinical trials, in which the role of immunotherapy as monotherapy was confirmed only for pembrolizumab in patients with PD-L1 expression ≥50%. These data were analysed in this paper, focusing on the implications in clinical practice and how to use them to an accurate clinical benefit of patients with advanced NSCLC. We report a review based on a MEDLINE/PubMed, searched for randomised phase 2/3 trials evaluating immune checkpoint inhibitors and NSCLC, that moved to an approval from Food and Drug Administration (FDA) and European Medicine Agency (EMA). The evidence discussed in this manuscript and the final therapeutic algorithm, coming out from an International Experts Panel Meeting of the Italian Association of Thoracic Oncology.

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At a recent conference on ‘ Medical ethics in the 70 years since the Nuremberg Code’ in Vienna, the task of a final panel of experts was to discuss the question whether to use, or not to use, data gained from coercive medical research in National Socialist Germany. Specific examples debated were the poison gas experiments by Professor Otto Bickenbach,1 and the Pernkopf atlas of Topographical Anatomy. In both instances, it became quickly evident that the question was not so much whether to use or not to use, as indeed, both of these sets of data have been used in the past and may currently still be in use. Rather, the core question seemed to be that of transparency: the need to lay open the origin of data in any publication on human subject research, be it research on the dead or studies of the living. At this point, a member of the audience asked how journal editors dealing with a global and diverse scientific community can decisively evaluate the origin of data from human subject research submitted for publication, and how editors can ascertain that samples of human tissues stem from ethical sources. It should be surprising that, in times of Institutional Review Boards (IRBs), multitudes of editorial guidelines for scientific journals, and a long-standing debate on the duties of journal editors,* uncertainty on this issue still remains. However, the increasing interconnectedness of scientific research around the world may require a new debate on the essential content and limits of common core ethical values in human research. In 1992, Marcia Angell, then Executive Editor of the New England Journal of Medicine , discussed the question of ethical uncertainty in her landmark paper on editorial responsibilities, and stressed the need for close editorial scrutiny even in cases of …

Whenever we approach the problem of classifying and ranking the clinical benefit of any therapy in oncology, we immediately face a number of problems. Some of these can be overcome, but some others do not appear to have a solution, given the complexity of the matter. In our recent papers on how to raise the bar for anticancer drug approval,1 2 we called for at least four clear distinctions in approaching this task. 1. The need to distinguish between the palliative situation and the adjuvant setting. In fact, the benefit of extending life or improving its quality, palliating tumour-related symptoms or extending progression-free survival (PFS) are all on a qualitatively different plan compared with the benefit of improving the cure rate of a resected neoplasm or even extending the disease-free survival (DFS); DFS, in fact, represents ‘life, thinking of being cured.’ No quantitative correlation can be established between the two ‘worlds’ of oncology (curative and palliative) and their specific treatment end points. Clearly, different scales must be used to measure the benefit of treatment in these two different conditions. 2. If we limit the effort of ranking the clinical benefit to the advanced, non-curative setting, another relevant distinction is the relative weight of the different end points. Clearly, extending life, overall survival (OS) and improving quality of life (QoL) rank first. Then come PFS and response rate (RR). The other patient-reported outcomes in general rank in-between, depending on the setting. But how much OS a patient may be ready to trade for just extending PFS or improving the other mentioned end points remains highly subjective. Hence, any equivalence level between these end points is highly variable and arbitrary. 3. Because of the previous observation regarding the impossibility to establish an objective correlation between the benefit in OS and that afforded to patients by PFS, we concentrated our efforts to rank …

Upper tract urothelial carcinomas (UTUCs) consist of 5%-10% of all urothelial carcinomas, the rest being urothelial carcinomas of the bladder (UCB). There is increasing evidence to show that UTUC is a distinct disease entity from UCB based on phenotypical and genotypical (genetic and epigenetic) differences. This may account for why the natural history of UTUC is different from that of UCB, with >60% of UTUCs and only 15%-25% of UCB presenting with invasion at diagnosis. Management of UTUC is thus different from UCB in a variety of ways, ranging from surgical management, postoperative instillation therapy, postoperative surveillance and medical management (neoadjuvant and adjuvant chemotherapy). This review paper aims to highlight these differences with an emphasis on the distinct management of UTUC, along with the latest updates.

Introduction Manchester Cancer Research Centre (MCRC) has established an MTB to facilitate precision medicine decision-making within the TARGET trial (Tumour chAracterisation to Guide Experimental Targeted Therapy). The MTB meets monthly to review clinical data and next generation sequencing (NGS) results from tumour tissue and circulating DNA (ctDNA) for patients being considered for early phase clinical trials. Initially the MTB relied on multiple paper reports. Here we present eTARGET, a digital solution developed by the digital Experimental Cancer Medicine Team (digitalECMT), which integrates clinical and genomic NGS data to facilitate decision-making for matching patients with clinical trials. Material and methods The digitalECMT explored data sources and existing reports to define end-user and data requirements. Following a successful prototype, a beta version was developed. Created in Microsoft Azure, a secure cloud computing platform, components included a storage account for data upload from three different sources, and a database for storing and integrating the data. The solution enabled automated extraction of individual pseudonymised clinical and genomic data. In addition, a web application to view the data was developed with clinical input. Results and discussions The beta version of eTARGET went online in October 2017 and has been utilised at 5 MTB meetings for 55 patient cases. This portal interface presents patient characteristics, treatment history and genomic data. The portal can be viewed remotely, across multiple locations, where all attendees see the same view. eTARGET has enabled the MTB to review individual patient data in a single portal, capture meeting outcomes in real-time and upload to the electronic patient record. Decisions regarding significant variants, trial matching or requirements for further analytical or translational analyses are captured. Conclusion eTARGET has shown that a digital solution can be implemented to overcome the challenge of integrating data from disparate sources in different organisations to create a single view of patient clinical and genomic data. We have shown the utility of eTARGET in a hospital setting to support decision-making for an MTB. The eTARGET project opens the possibility of wider MTB participation including cross centre collaboration. Next steps are to enhance the software to visualise the global molecular dataset and serial changes in NGS profiles on treatment.

Introduction Predatory journals harm the integrity of science as principles of ‘good scientific practice’ are bypassed by omitting a proper peer-review process. Therefore, we aimed to explore the awareness of predatory journals among oncologists.Methods An online survey among oncologists working in Germany or Austria of various professional surroundings was conducted between October 2018 and April 2019.Results One hundred and eighty-eight participants (55 women (29.2%), 128 men (68.1%)) completed the questionnaire. 41 (21.8%) participants indicated to work in a hospital, 24 (12.8%) in private practice and 112 (59.6%) in a university hospital. 98.9% of participants indicated to actively read scientific articles and consider them in clinical decision-making (96.3%). 90.4% of participants indicated to have scientific experience by publishing papers in journals with peer-review system. The open-access system was known by 170 (90.4%), predatory journals by 131 (69.7%) and Beall’s list by 52 participants (27.7%). Predatory journals were more likely to be known by participants with a higher number of publications (p

Introduction The B6;129- Rag2 tm1Fwa IL2rg tm1Rsky /DwlHsd (R2G2) knockout mouse was developed by backcrossing an IL2rg (common gamma) knockout model to a RAG2 (recombinase activating gene) knockout model. The resulting mouse lacks various cytokines including IL-2, IL-4, IL-7, IL-9 and IL-15. In addition, this model lacks B cells, T cells, NK cells and has a deficit in lymphocyte development. This model was developed to provide another immunodeficient option for the oncology and immunology fields. The literature supports better tolerability of DNA damaging oncology treatments for models that do not carry the SCID mutation. We have already reported in a white paper that the R2G2 mouse model is more tolerant of whole body radiation than a model with the SCID mutation. Herein we describe a study examining chemotherapeutic tolerability of common DNA damaging oncology drugs including 5-fluorouracil (5-FU), doxorubicin (Doxo), and cyclophosphamide (CTX) (n=10 per group). Material and methods 5-FU was given at 30, 60 or 100 mg/kg, intraperitoneally, twice weekly for five weeks. Doxo was given at 2 or 5 mg/kg, intraperitoneally, once weekly for three weeks. CTX was given at 100 or 140 mg/kg intraperitoneally, once weekly for three weeks. The low dose was chosen based on the average dose used in immunodeficient mouse models and the high dose was chosen based on the average dose used in immunocompetent mouse models. This was done to determine if the R2G2 mouse model can tolerate higher doses of these chemotherapeutic agents compared to other immunodeficient mouse models. Results and discussions Results show that the R2G2 mouse model tolerates higher doses of these chemotherapeutic drugs than doses found in the literature for SCID models. Exogenous oestrogen tolerance is another common concern in oncology research as some immunodeficient mouse models cannot tolerate the subcutaneous oestrogen pellets, developing negative secondary effects resulting in removal from study. We performed an oestrogen pellet dose response study using four doses of 60 day release 17-β estradiol pellets at 0.18, 0.36, 0.72, and 1.7 mg/pellet (n=10 per group). R2G2 mice show dose dependent effects of oestrogen on morbidity. These data will allow researchers to determine the optimal dose for use in the R2G2 model. Conclusion In conclusion, these data support that the R2G2 mouse model may be a good alternative to SCID models when administering DNA damaging chemotherapies or when oestrogen supplementation is required for xenograft growth.

Triple negative breast cancer (TNBC) is a type of breast cancer (BC) that does not express the oestrogen and the progesterone receptors and the human epidermal growth factor receptor type 2 (HER2). Since there are no positive markers to reliably classify TNBC, these tumours are not yet treated with targeted therapies. Perhaps for this reason they are the most aggressive form of breast carcinomas. However, the clinical observation that these patients do not carry a uniformly dismal prognosis, coupled with data coming from pathology and epidemiology, suggests that this negative definition is not capturing a single clinical entity, but several. We critically evaluate this evidence in this paper, reviewing clinical and epidemiological data and new studies that aim to subclassify TNBC. Moreover, evidence on the role of tumour infiltrating lymphocytes (TILs) on TNBC progression, response to chemotherapy and patient outcome have been published. The heterogeneity, observed even at TILs level, highlights the idea that TNBC is much more than a single disease with a unique treatment. The exploration of the immune environment present at the tumour site could indeed help in answering the question ‘How many diseases is TNBC’ and will help to define prognosis and eventually develop new therapies, by stimulating the immune effector cells or by inhibiting immunological repressor molecules. In this review, we focus on the prospect of the patient’s diverse immune signatures within the tumour as potential biomarkers and how they could be modulated to fight the disease.

Please click here to see linked paper Background To investigate the potential predictors of response to regorafenib, in chemorefractory metastatic colorectal cancer (mCRC) patients with long-term efficacy from regorafenib treatment. Methods Retrospective, single institution analysis of patients with chemorefractory mCRC treated with regorafenib, in clinical practice setting. 123 patients were treated and stratified into two groups according to number of cycles received (

When European Society for Medical Oncology (ESMO) former president Rolf Stahel called me on this memorable evening of September 2015 asking me whether I would be willing to become the editor-in-chief of the newly founded internet-only open-access journal named ESMO Open: Cancer Horizons (the latter addition being an invention during an animated talk with the current ESMO president Fortunato Ciardiello) and when I heard myself say, “well, of course, with pleasure; honoured to serve ESMO which has been ‘my’ society and in the centre of my attention for many years”, I did not fully realise what was going to happen and what was going to follow, mainly a breathless development and most wonderful endeavour and experience in setting up a new journal. SETTING UP A NEW JOURNAL! This meant meeting and talking to countless people to set up the structure and function of the Journal (first of all: thank you, Lewis Rowett and Henry Spilberg), generating a concept on what the Journal would be standing for, understanding the potential of an internet-based publication (thank you, Anna Berghoff), attracting — most importantly! — papers (thank you, Jean-Charles Soria for supporting us via Annals of Oncology ), inviting friends who would be …

Laparoscopic surgery for the treatment of right colon cancer has rapidly evolved over the past few years. This procedure is considered as feasible and effective in terms of short-term and long-term outcomes. Laparoscopic right colectomy (LRC) is performed by a small number of surgeons and, in most of cases, it was performed with an extracorporeal anastomosis.1 The recent ESMO guidelines with a Level of Evidence (LE) IV reported that for right-sided colonic cancers, the benefits of laparoscopic approach are less obvious since anastomosis must be hand sewn, which requires a laparotomy.2 The current state of the art for the treatment of the right colon cancers as reported by Fabozzi et al.3 in their papers, by right laparoscopic colectomy with intracorporeal anastomosis despite the technical challenging. However, in the past few years, many studies comparing the intracorporeal anastomosis (IA) versus the extracorporeal anastomosis (EA) in LRC were conducted1 ,4–8 with …

Our level of understanding of the biology of cancer at this point in time is amazing and continues to increase. Each year we know more and more about the fundamental mechanisms of tumour growth and progression of the disease. Thanks to this improved knowledge we are able to evaluate new drugs that in some instances are very effective. We even have biomarkers that define a population of patients that may benefit more from the treatment. In some other patients we don't have such biomarkers and the benefit is only incremental. This does not mean that the treatment is not good, but the maximum effect can be considered very modest. The European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) offers an opportunity to grade the effect of these new drugs in each tumour and even in each indication. The tool enables us to gather important information on the real impact of any drug in the different settings in which a drug may be approved. Using data from phase III clinical trials or meta-analyses, the tool uses a rational, structured and consistent approach to derive a relative ranking of the magnitude of benefit than can be anticipated from any new treatment. As the authors of the paper in Annals of Oncology in May 2015 concluded, “the ESMO-MCBS is an important first step to the major ongoing task of evaluating value in cancer care …

Background This is an appraisal of the impact of cited research evidence underpinning the development of cancer clinical practice guidelines (CPGs) by the professional bodies of the European Society for Medical Oncology (ESMO), the National Institute for Health and Care Excellence (NICE) and the Scottish Intercollegiate Guidelines Network (SIGN). Methods A total of 101 CPGs were identified from ESMO, NICE and SIGN websites across 13 cancer sites. Their 9486 cited references were downloaded from the Web of Science Clarivate Group database, analysed on Excel (2016) using Visual Basic Application macros and imported onto SPSS (V.24.0) for statistical tests. Results ESMO CPGs mostly cited research from Western Europe, while the NICE and SIGN ones from the UK, Canada, Australia and Scandinavian countries. The ESMO CPGs cited more recent and basic research (eg, drugs treatment), in comparison with NICE and SIGN CPGs where older and more clinical research (eg, surgery) papers were referenced. This chronological difference in the evidence base is also in line with that ESMO has a shorter gap between the publication of the research and its citation on the CPGs. It was demonstrated that ESMO CPGs report more chemotherapy research, while the NICE and SIGN CPGs report more surgery, with the results being statistically significant. Conclusions We showed that ESMO, NICE and SIGN differ in their evidence base of CPGs. Healthcare professionals should be aware of this heterogeneity in effective decision-making of tailored treatments to patients, irrespective of geographic location across Europe.