Recommendations for the use of next-generation sequencing (NGS) for patients with advanced cancer in 2024: a report from the ESMO Precision Medicine Working Group.

BACKGROUND: Advancements in the field of precision medicine have prompted the European Society for Medical Oncology (ESMO) Precision Medicine Working Group to update the recommendations for the use of tumour next-generation sequencing (NGS) for patients with advanced cancers in routine practice. METHODS: The group discussed the clinical impact of tumour NGS in guiding treatment decision using the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT) considering cost-effectiveness and accessibility. RESULTS: As for 2020 recommendations, ESMO recommends running tumour NGS in advanced non-squamous non-small-cell lung cancer, prostate cancer, colorectal cancer, cholangiocarcinoma, and ovarian cancer. Moreover, it is recommended to carry out tumour NGS in clinical research centres and under specific circumstances discussed with patients. In this updated report, the consensus within the group has led to an expansion of the recommendations to encompass patients with advanced breast cancer and rare tumours such as gastrointestinal stromal tumours, sarcoma, thyroid cancer, and cancer of unknown primary. Finally, ESMO recommends carrying out tumour NGS to detect tumour-agnostic alterations in patients with metastatic cancers where access to matched therapies is available. CONCLUSION: Tumour NGS is increasingly expanding its scope and application within oncology with the aim of enhancing the efficacy of precision medicine for patients with cancer.

Role of molecular genetics in the clinical management of cholangiocarcinoma.

The incidence of cholangiocarcinoma (CCA) has steadily increased during the past 20 years, and mortality is increasing. The majority of patients with CCA have advanced or metastatic disease at diagnosis, and treatment options for unresectable disease are limited, resulting in poor prognosis. However, recent identification of targetable genomic alterations has expanded treatment options for eligible patients. Given the importance of early and accurate diagnosis in optimizing patient outcomes, this review discusses best practices in CCA diagnosis, with a focus on categorizing molecular genetics and available targeted therapies. Imaging and staging of CCAs are discussed, as well as recommended biopsy collection techniques, and molecular and genomic profiling methodologies, which have become increasingly important as molecular biomarker data accumulate. Approved agents targeting actionable genomic alterations specifically in patients with CCA include ivosidenib for tumors harboring IDH1 mutations, and infigratinib and pemigatinib for those with FGFR2 fusions. Other agents currently under development in this indication have shown promising results, which are presented here.

Integrative molecular analysis of combined small-cell lung carcinomas identifies major subtypes with different therapeutic opportunities.

BACKGROUND: Combined small-cell lung cancer (C-SCLC) is composed of SCLC admixed with a non-small-cell cancer component. They currently receive the same treatment as SCLC. The recent evidence that SCLC may belong to either of two lineages, neuroendocrine (NE) or non-NE, with different vulnerability to specific cell death pathways such as ferroptosis, opens new therapeutic opportunities also for C-SCLC. MATERIALS AND METHODS: Thirteen C-SCLCs, including five with adenocarcinoma (CoADC), five with large-cell neuroendocrine carcinoma (CoLCNEC) and three with squamous cell carcinoma (CoSQC) components, were assessed for alterations in 409 genes and transcriptomic profiling of 20 815 genes. RESULTS: All 13 cases harbored TP53 (12 cases) and/or RB1 (7 cases) inactivation, which was accompanied by mutated KRAS in 4 and PTEN in 3 cases. Potentially targetable alterations included two KRAS G12C, two PIK3CA and one EGFR mutations. Comparison of C-SCLC transcriptomes with those of 57 pure histology lung cancers (17 ADCs, 20 SQCs, 11 LCNECs, 9 SCLCs) showed that CoLCNEC and CoADC constituted a standalone group of NE tumors, while CoSQC transcriptional setup was overlapping that of pure SQC. Using transcriptional signatures of NE versus non-NE SCLC as classifier, CoLCNEC was clearly NE while CoSQC was strongly non-NE and CoADC exhibited a heterogeneous phenotype. Similarly, using ferroptosis sensitivity/resistance markers, CoSQC was classified as sensitive (as expected for non-NE), CoLCNEC as resistant (as expected for NE) and CoADC showed a heterogeneous pattern. CONCLUSIONS: These data support routine molecular profiling of C-SCLC to search for targetable driver alterations and to precisely classify them according to therapeutically relevant subgroups (e.g. NE versus non-NE).

Evaluation of Discomfort in Nasopharyngeal Swab Specimen Collection for SARS-CoV-2 Diagnosis.

BACKGROUND: The rapid spread of COVID-19 worldwide has impo-sed the need to identify a test that quickly recognizes affected subjects, both symptomatic and asymptomatic. The most reliable option has been proven to be the RT-PCR, which allows to detect virus RNA on a specimen from a high viral load site, such as nasopharynx. Nasopha-ryngeal sample collection is possible by means of a nasopharyngeal swab (NPS) and is a practical and relatively non-invasive technique, but rather bothersome for the recipient. AIM: The aim of the present study is to evaluate the discomfort evoked during NPS. MATERIALS AND METHODS: We surveyed 429 patients receiving NPS before hospitalization or other procedures non related to COVID-19. For each one we noted the discomfort level felt during the swab using a 11-point numeric rating scale (NRS) for pain and the total time needed for the procedure to be taken. Sex, age, smoking status and positive history of previous swab have been taken into account. RESULTS: We found that, among the variables, sex had a statistically significant impact on the perceived discomfort of nasal swab, with females experiencing slightly more discomfort. CONCLUSIONS: NPS is largely a none-to-minimum discomfort in-ducing procedure. The differences in perceived discomfort could be explained based on anatomical features, and should remark the need for a tailored and anatomy-oriented approach in each patient.

Gallbladder disease and pancreatic cancer risk: a multicentric case-control European study.

BACKGROUND AND AIMS: The overall evidence on the association between gallbladder conditions (GBC: gallstones and cholecystectomy) and pancreatic cancer (PC) is inconsistent. To our knowledge, no previous investigations considered the role of tumour characteristics on this association. Thus, we aimed to assess the association between self-reported GBC and PC risk, by focussing on timing to PC diagnosis and tumour features (stage, location, and resection). METHODS: Data derived from a European case-control study conducted between 2009 and 2014 including 1431 PC cases and 1090 controls. We used unconditional logistic regression models to estimate odds ratios (ORs) and corresponding 95% confidence intervals (CIs) adjusted for recognized confounders. RESULTS: Overall, 298 (20.8%) cases and 127 (11.6%) controls reported to have had GBC, corresponding to an OR of 1.70 (95% CI 1.33-2.16). The ORs were 4.84 (95% CI 2.96-7.89) for GBC diagnosed <3 years before PC and 1.06 (95% CI 0.79-1.41) for ≥3 years. The risk was slightly higher for stage I/II (OR = 1.71, 95% CI 1.15-2.55) vs. stage III/IV tumours (OR = 1.23, 95% CI 0.87-1.76); for tumours sited in the head of the pancreas (OR = 1.59, 95% CI 1.13-2.24) vs. tumours located at the body/tail (OR = 1.02, 95% CI 0.62-1.68); and for tumours surgically resected (OR = 1.69, 95% CI 1.14-2.51) vs. non-resected tumours (OR = 1.25, 95% CI 0.88-1.78). The corresponding ORs for GBC diagnosed ≥3 years prior PC were close to unity. CONCLUSION: Our study supports the association between GBC and PC. Given the time-risk pattern observed, however, this relationship may be non-causal and, partly or largely, due to diagnostic attention and/or reverse causation.

Clinical presentation, genotype-phenotype correlations, and outcome of pancreatic neuroendocrine tumors in Von Hippel-Lindau syndrome.

PURPOSE: Data regarding the clinical management and follow-up of pancreatic neuroendocrine tumors (PanNETs) associated with Von Hippel-Lindau (VHL) syndrome are limited. This study aimed to assess clinical presentation, genotype-phenotype correlations, treatment and prognosis of PanNETs in a series of VHL syndrome patients. METHODS: Retrospective analysis of data of patients observed between 2005 and 2020. RESULTS: Seventeen patients, including 12 probands and 5 relatives (mean age 30.8 ± 18.4; 7 males), were recruited. PanNETs were found in 13/17 patients (77.5%) at a median age of 37 years: 4/13 (30.7%) at the time of VHL diagnosis and 9 (69.3%) during follow up. Six (46.1%) PanNET patients underwent surgery, whereas seven were conservatively treated (mean tumor diameter: 40 ± 10.9 vs. 15 ± 5.3 mm respectively). Four patients (30.7%) had lymph node metastases and a mean tumor diameter significantly larger than the nonmetastatic PanNETs (44.2 ± 9.3 vs. 17.4 ± 7 mm, p = 0.00049, respectively). Five (83.3%) operated patients had stable disease after a median follow up of 3 years whereas one patient showed liver metastases. Six (85.7%) non-resected PanNETs were stable after a median follow-up of 2 years, whereas one patient developed a new small PanNET and a slight increase in diameter of a pre-existing PanNET. No correlation was found between the type of germline mutation and malignant behavior of PanNETs. CONCLUSIONS: PanNETs are a common disease of the VHL syndrome and can be the presenting feature. Tumor size rather than genetic mutation is a prognostic factor of malignancy.

ESMO recommendations on the standard methods to detect RET fusions and mutations in daily practice and clinical research.

Aberrant activation of RET is a critical driver of growth and proliferation in diverse solid tumours. Multikinase inhibitors (MKIs) showing anti-RET activities have been tested in RET-altered tumours with variable results. The low target specificity with consequent increase in side-effects and off-target toxicities resulting in dose reduction and drug discontinuation are some of the major issues with MKIs. To overcome these issues, new selective RET inhibitors such as pralsetinib (BLU-667) and selpercatinib (LOXO-292) have been developed in clinical trials, with selpercatinib recently approved by the Food and Drug Administration (FDA). The results of these trials showed marked and durable antitumour activity and manageable toxicity profiles in patients with RET-altered tumours. The European Society for Medical Oncology (ESMO) Translational Research and Precision Medicine Working Group (TR and PM WG) launched a collaborative project to review the available methods for the detection of RET gene alterations, their potential applications and strategies for the implementation of a rational approach for the detection of RET fusion genes and mutations in human malignancies. We present here recommendations for the routine clinical detection of targetable RET rearrangements and mutations.

Is Laparoscopic CME Right Hemicolectomy an Optimal Indication for NET of the Right Colon and Terminal Ileum?

PURPOSE: Since lymphadenectomy is crucial in midgut neuroendocrine tumor (NET) surgery, we adopted laparoscopic CME right hemicolectomy (LRH-CME) for the treatment of right colon and terminal ileum NETs. In this report, we present a series of nine cases of terminal midgut NETs (TM-NETs) treated by LRH-CME with a video demonstrating oncological principles and the surgical technique. METHODS: From September 2014 to November 2019, nine patients affected by TM-NETs underwent LRH-CME at the Unit of General and Hepatobiliary Surgery, University of Verona Hospital Trust, ENETS Center of Excellence. Clinicopathological data, post-operative and oncological outcomes were prospectively collected and analyzed. RESULTS: Tumors were in ileocecal valve or terminal ileum (5 cases), right colon (3 cases), and appendix (one case). Surgery had a curative intent (R0 resection) in 7 cases. Surgical debulking was required in 2 metastatic cases. Mean surgical time was 212 + 41 min and blood loss 47 + 24 mL. No postoperative mortality was observed. Post-operative course was uneventful in all except one case (Clavien-Dindo III). Median number of harvested lymph nodes was 21 (range, 11-31) and eight out of 9 patients were node positive (median 3, range 0-6). At a median follow-up of 18 months (range, 6-50), none of the patients suffered from mesenteric locoregional recurrence and all R0 resected patients were disease-free. CONCLUSIONS: Terminal midgut NETs represent an optimal indication for LRH-CME which increases the chance of complete resection and allows optimal lymphadenectomy. In expert hands, laparoscopic approach should be favored in consideration of good short-term outcomes.

Recommendations for the use of next-generation sequencing (NGS) for patients with metastatic cancers: a report from the ESMO Precision Medicine Working Group.

Next-generation sequencing (NGS) allows sequencing of a high number of nucleotides in a short time frame at an affordable cost. While this technology has been widely implemented, there are no recommendations from scientific societies about its use in oncology practice. The European Society for Medical Oncology (ESMO) is proposing three levels of recommendations for the use of NGS. Based on the current evidence, ESMO recommends routine use of NGS on tumour samples in advanced non-squamous non-small-cell lung cancer (NSCLC), prostate cancers, ovarian cancers and cholangiocarcinoma. In these tumours, large multigene panels could be used if they add acceptable extra cost compared with small panels. In colon cancers, NGS could be an alternative to PCR. In addition, based on the KN158 trial and considering that patients with endometrial and small-cell lung cancers should have broad access to anti-programmed cell death 1 (anti-PD1) antibodies, it is recommended to test tumour mutational burden (TMB) in cervical cancers, well- and moderately-differentiated neuroendocrine tumours, salivary cancers, thyroid cancers and vulvar cancers, as TMB-high predicted response to pembrolizumab in these cancers. Outside the indications of multigene panels, and considering that the use of large panels of genes could lead to few clinically meaningful responders, ESMO acknowledges that a patient and a doctor could decide together to order a large panel of genes, pending no extra cost for the public health care system and if the patient is informed about the low likelihood of benefit. ESMO recommends that the use of off-label drugs matched to genomics is done only if an access programme and a procedure of decision has been developed at the national or regional level. Finally, ESMO recommends that clinical research centres develop multigene sequencing as a tool to screen patients eligible for clinical trials and to accelerate drug development, and prospectively capture the data that could further inform how to optimise the use of this technology.

Impact of COVID-19 on otolaryngology in Italy: a commentary from the COVID-19 task force of the Young Otolaryngologists of the Italian Society of Otolaryngology.

OBJECTIVE: The ongoing pandemic of coronavirus disease 2019 is having a dramatic effect on most medical disciplines. Otolaryngology Head and Neck Surgery is one of the most engaged disciplines, and otolaryngology specialists are facing a radical change of their role and daily activities that will have severe impact on the return to the ordinary. In this paper, the COVID-19 Task Force of the Young Otolaryngologists of the Italian Society of Otolaryngology comment on the changes that occurred for otolaryngology in Italy during the pandemic. Changes include organizational rearrangement of Otolaryngology Units, with merges and closures that affected a significant portion of them; reallocation of otolaryngology personnel, mainly to COVID-19 wards; reduction of elective clinical and surgical activity, that was mainly limited to oncology and emergency procedures; and execution of screening procedures for SARS-CoV-2 among healthcare providers and patients in otolaryngology units in Italy.

Pleomorphic Adenoma of the Parotid Gland and Ipsilateral Thyroid Incidentaloma: Report of A Rare Case With Review of Literature.

BACKGROUND: Pleomorphic adenomas are benign tumors of the salivary glands that mainly affect the lower pole of the superficial lobe of the parotid gland. The term "pleomorphic" refers to the epithelial and connective origin of the mass. The clinical presentation is typically that of asymptomatic swelling which increases in volume. Therapy consists in surgical removal of the tumor mass by parotidectomy with nerve preservation. CASE DETAILS: This clinical case describes an interesting case of pleomorphic adenoma of the parotid gland in a 62-year-old patient. The patient presented with a long history of an asymptomatic mildly worsening swelling of the left parotid region. The peculiarity of the clinical case is the dimension of the adenoma (9x5x9 cm) and the presence of a thyroid incidentaloma (TI), consisting of a thyroid multinodular goiter composed of nodules, the largest of which measured 8 cm in diameter. This mass dislocated the laryngotracheal axis, compressed the larynx and caused the reduction of the respiratory space, making orotracheal intubation difficult and determining the need to perform a tracheotomy. CONCLUSION: Benign pleomorphic adenomas can potentially reach large sizes if untreated. Socio-economic problems may be the reason for late diagnosis.

Acinic cell carcinoma of the parotid gland: from pathogenesis to management: a literature review.

PURPOSE: Acinic cell carcinoma (ACCs) is uncommon malignant epithelial neoplasm of the salivary glands; the most common presentation is a well-defined painless solid mass. Diagnosis of ACCs is frequently complicated, due to its similarity with benign tumors. METHODS: A review of the literature available on ACCs was carried out. Studies were sourced from PubMed with searching of relevant headings and sub-headings and cross-referencing. RESULTS: There are no clear characteristics of ACCs found on CT, MRI and ultrasound imaging. The management of the ACC, a rare malignancy of the parotid gland, is often difficult and controversial. Radical surgery is the best treatment option. The role of radiotherapy remains controversial: the precise indications and oncologic effects of adjuvant radiotherapy in ACC of the parotid gland are not well known. There is insufficient literature regarding the chemotherapy for metastatic ACC. CONCLUSION: Knowledge about ACC, a rare malignancy of parotid gland, has changed over the past few decades. More clinical randomized works would be needed, both to assess the real effectiveness of radio and chemotherapy and to have an unanimous consensus about their indications.

Pharmacological, Surgical and Diagnostic Innovations in Meniere's Disease: A Review.

PURPOSE: To investigate literature about pharmacological, surgical, and diagnostic innovations for Meniere's Disease (MD). SUMMARY: Meniere's disease is an inner ear disorder characterized by the presence of endolymphatic hydrops in the inner ear and symptomatology of recurrent and debilitating vertigo attacks, tinnitus, aural fullness, and fluctuating sensorineural hearing loss. Although many therapeutic options for MD have been proposed during years, no consensus has been reached by the scientific community. In the last decade, many therapeutic options have been proposed, as intratympanic steroid, intratympanic gentamicin, and intravenous glycerol. Recently, the role of the antisecretory factor in the diet of MD patients have been investigated. Surgery is recommended for intractable MD; some authors proposed new approaches including transcanal endoscopic infracochlear vestibular neurectomy, new marsupiliazation technique in sac surgery, and tenotomy of the stapedius and tensor tympani muscles.

ESMO recommendations on microsatellite instability testing for immunotherapy in cancer, and its relationship with PD-1/PD-L1 expression and tumour mutational burden: a systematic review-based approach.

BACKGROUND: Cancers with a defective DNA mismatch repair (dMMR) system contain thousands of mutations most frequently located in monomorphic microsatellites and are thereby defined as having microsatellite instability (MSI). Therefore, MSI is a marker of dMMR. MSI/dMMR can be identified using immunohistochemistry to detect loss of MMR proteins and/or molecular tests to show microsatellite alterations. Together with tumour mutational burden (TMB) and PD-1/PD-L1 expression, it plays a role as a predictive biomarker for immunotherapy. METHODS: To define best practices to implement the detection of dMMR tumours in clinical practice, the ESMO Translational Research and Precision Medicine Working Group launched a collaborative project, based on a systematic review-approach, to generate consensus recommendations on the: (i) definitions related to the concept of MSI/dMMR; (ii) methods of MSI/dMMR testing and (iii) relationships between MSI, TMB and PD-1/PD-L1 expression. RESULTS: The MSI-related definitions, for which a consensus frame-work was used to establish definitions, included: 'microsatellites', 'MSI', 'DNA mismatch repair' and 'features of MSI tumour'. This consensus also provides recommendations on MSI testing; immunohistochemistry for the mismatch repair proteins MLH1, MSH2, MSH6 and PMS2 represents the first action to assess MSI/dMMR (consensus with strong agreement); the second method of MSI/dMMR testing is represented by polymerase chain reaction (PCR)-based assessment of microsatellite alterations using five microsatellite markers including at least BAT-25 and BAT-26 (strong agreement). Next-generation sequencing, coupling MSI and TMB analysis, may represent a decisive tool for selecting patients for immunotherapy, for common or rare cancers not belonging to the spectrum of Lynch syndrome (very strong agreement). The relationships between MSI, TMB and PD-1/PD-L1 expression are complex, and differ according to tumour types. CONCLUSIONS: This ESMO initiative is a response to the urgent questions raised by the growing success of immunotherapy and provides also important insights on the relationships between MSI, TMB and PD-1/PD-L1.

The prognostic significance of E-cadherin expression in laryngeal squamous-cell carcinoma: a systematic review.

The aim of this study was to systematically review publications that investigated the prognostic role of E-cadherin immunostaining in patients affected by laryngeal squamous cell carcinoma. An appropriate string was run on PubMed to retrieve articles dealing with this topic. A double cross-check was performed on citations and full-text articles by two authors independently to analyse all manuscripts and perform a comprehensive quality assessment. Among 89 abstracts identified, 13 articles were included. These studies reported on 1,121 patients with histologically confirmed diagnosis of laryngeal squamous cell carcinoma. Overall, there were 10 studies that showed a significant correlation between E-cadherin immunohistochemical expression and at least one of the clinical and histopathological parameters considered by the authors. In particular E-cadherin expression was significantly associated with N stage (five studies), grading (four studies) and disease-free survival/disease-specific survival (six studies). In conclusion, the findings of our review appear similar to the results published by other authors on the putative role of E-cadherin in progression of malignancy. In fact, for laryngeal squamous cell carcinoma it seems that lower levels of E-cadherin correlate with increased tumoural aggressiveness and worse prognosis. Nevertheless, further high-quality prospective studies should be carried out to clarify if E-cadherin expression may be considered as an independent prognostic factor for patients affected by laryngeal cancer.

Transcriptomic analysis and mutational status of IDH1 in paired primary-recurrent intrahepatic cholangiocarcinoma.

BACKGROUND: Effective target therapies for intrahepatic cholangiocarcinoma (ICC) have not been identified so far. One of the reasons may be the genetic evolution from primary (PR) to recurrent (REC) tumors. We aim to identify peculiar characteristics and to select potential targets specific for recurrent tumors. Eighteen ICC paired PR and REC tumors were collected from 5 Italian Centers. Eleven pairs were analyzed for gene expression profiling and 16 for mutational status of IDH1. For one pair, deep mutational analysis by Next Generation Sequencing was also carried out. An independent cohort of patients was used for validation. RESULTS: Two class-paired comparison yielded 315 differentially expressed genes between REC and PR tumors. Up-regulated genes in RECs are involved in RNA/DNA processing, cell cycle, epithelial to mesenchymal transition (EMT), resistance to apoptosis, and cytoskeleton remodeling. Down-regulated genes participate to epithelial cell differentiation, proteolysis, apoptotic, immune response, and inflammatory processes. A 24 gene signature is able to discriminate RECs from PRs in an independent cohort; FANCG is statistically associated with survival in the chol-TCGA dataset. IDH1 was mutated in the RECs of five patients; 4 of them displayed the mutation only in RECs. Deep sequencing performed in one patient confirmed the IDH1 mutation in REC. CONCLUSIONS: RECs are enriched for genes involved in EMT, resistance to apoptosis, and cytoskeleton remodeling. Key players of these pathways might be considered druggable targets in RECs. IDH1 is mutated in 30% of RECs, becoming both a marker of progression and a target for therapy.

Risk of pancreatic cancer associated with family history of cancer and other medical conditions by accounting for smoking among relatives.

Background: Family history (FH) of pancreatic cancer (PC) has been associated with an increased risk of PC, but little is known regarding the role of inherited/environmental factors or that of FH of other comorbidities in PC risk. We aimed to address these issues using multiple methodological approaches. Methods: Case-control study including 1431 PC cases and 1090 controls and a reconstructed-cohort study (N = 16 747) made up of their first-degree relatives (FDR). Logistic regression was used to evaluate PC risk associated with FH of cancer, diabetes, allergies, asthma, cystic fibrosis and chronic pancreatitis by relative type and number of affected relatives, by smoking status and other potential effect modifiers, and by tumour stage and location. Familial aggregation of cancer was assessed within the cohort using Cox proportional hazard regression. Results: FH of PC was associated with an increased PC risk [odds ratio (OR) = 2.68; 95% confidence interval (CI): 2.27-4.06] when compared with cancer-free FH, the risk being greater when ≥ 2 FDRs suffered PC (OR = 3.88; 95% CI: 2.96-9.73) and among current smokers (OR = 3.16; 95% CI: 2.56-5.78, interaction FHPC*smoking P-value = 0.04). PC cumulative risk by age 75 was 2.2% among FDRs of cases and 0.7% in those of controls [hazard ratio (HR) = 2.42; 95% CI: 2.16-2.71]. PC risk was significantly associated with FH of cancer (OR = 1.30; 95% CI: 1.13-1.54) and diabetes (OR = 1.24; 95% CI: 1.01-1.52), but not with FH of other diseases. Conclusions: The concordant findings using both approaches strengthen the notion that FH of cancer, PC or diabetes confers a higher PC risk. Smoking notably increases PC risk associated with FH of PC. Further evaluation of these associations should be undertaken to guide PC prevention strategies.

The European Society for Medical Oncology (ESMO) Precision Medicine Glossary.

Background: Precision medicine is rapidly evolving within the field of oncology and has brought many new concepts and terminologies that are often poorly defined when first introduced, which may subsequently lead to miscommunication within the oncology community. The European Society for Medical Oncology (ESMO) recognises these challenges and is committed to support the adoption of precision medicine in oncology. To add clarity to the language used by oncologists and basic scientists within the context of precision medicine, the ESMO Translational Research and Personalised Medicine Working Group has developed a standardised glossary of relevant terms. Materials and methods: Relevant terms for inclusion in the glossary were identified via an ESMO member survey conducted in Autumn 2016, and by the ESMO Translational Research and Personalised Medicine Working Group members. Each term was defined by experts in the field, discussed and, if necessary, modified by the Working Group before reaching consensus approval. A literature search was carried out to determine which of the terms, 'precision medicine' and 'personalised medicine', is most appropriate to describe this field. Results: A total of 43 terms are included in the glossary, grouped into five main themes-(i) mechanisms of decision, (ii) characteristics of molecular alterations, (iii) tumour characteristics, (iv) clinical trials and statistics and (v) new research tools. The glossary classes 'precision medicine' or 'personalised medicine' as technically interchangeable but the term 'precision medicine' is favoured as it more accurately reflects the highly precise nature of new technologies that permit base pair resolution dissection of cancer genomes and is less likely to be misinterpreted. Conclusions: The ESMO Precision Medicine Glossary provides a resource to facilitate consistent communication in this field by clarifying and raising awareness of the language employed in cancer research and oncology practice. The glossary will be a dynamic entity, undergoing expansion and refinement over the coming years.