Precision oncology relies on precision diagnostics, and histopathological diagnosis, along with biomarker evaluation, currently represents the cornerstone for personalized treatment. In gastrointestinal neoplasms, diagnostic assessment and molecular profiling are often performed on biopsy tissue, which may be quantitatively/qualitatively limited. Therefore, appropriate sample management is essential to avoid unnecessary waste and to obtain all the information necessary for treatment planning. Several factors may significantly impact biomarker testing: (i) pre-analytical issues; (ii) heterogeneity in biomarker expression; (iii) lack of standardization in biomarker testing and evaluation. Moreover, in the metastatic setting, inadequate/incomplete clinical information can lead to inappropriate sample handling, with negative implications. The application of appropriate guidelines in testing and reporting biomarker status according to clinical context is, therefore, strongly encouraged. In this position paper, the Italian Group of Gastrointestinal Pathologists (GIPAD), a section of the Italian Society of Pathological Anatomy and Cytology (SIAPeC-IAP), aims to summarize all the clinical and pathological requirements for adequate assessment of prognostic and predictive biomarkers in the gastrointestinal oncology patient, from biopsy acquisition to diagnostic reporting.

Cancer predisposition syndromes (CPSs), including genetic tumour risk syndromes (genturis), are a heterogeneous group of genetic disorders characterised by an increased risk of developing tumours compared to the general population. CPSs raise reproductive issues for affected individuals because of the risk of passing the disease-causing genetic alterations on to offspring. The demand for reproductive counselling is often unmet due to the lack of sufficient healthcare professionals with the specialised knowledge, experience and skill. Based on a comprehensive literature review of 851 publications and expert consensus (multidisciplinary medical experts and patient representatives), the European Reference Network on genetic tumour risk syndromes (ERN GENTURIS) developed a guideline providing 16 recommendations for reproductive counselling in CPSs. The central recommendation is to offer reproductive counselling proactively to all individuals with a CPS and their relevant family members, together with psychological support and in multidisciplinary collaborations. This guideline aims to standardize the offer of reproductive counselling for individuals with a CPS across Europe, empowers healthcare professionals for their specific tasks, and helps patients dealing with their own challenges.

Unresectable stage III non-small cell lung cancer (NSCLC) exhibits substantial heterogeneity and complexity. The landmark LAURA and POLESTAR studies have established a standard therapeutic model involving targeted consolidation therapy with osimertinib or aumolertinib after definitive chemoradiotherapy for NSCLC patients harboring EGFR-sensitive mutations. However, treatment strategies for patients with other driver gene mutations (e.g., ALK fusions, ROS1 rearrangement) still lack robust support from high-level evidence-based medical study. To enhance the standardization of diagnosis and treatment for unresectable stage III driver-positive NSCLC patients, the Radiotherapy Committee of the Chinese Society of Clinical Oncology convened an expert working group. This group identified common clinical practice issues and conducted an in-depth, problem-oriented analysis of domestic and international guidelines alongside evidence-based medical data. Through multiple rounds of comprehensive discussion and expert voting, this consensus was jointly developed. It provides evidence-based recommendations addressing frequently encountered clinical questions regarding unresectable stage III driver-positive NSCLC, aiming to serve as a key reference for clinical practice.

Waldenström's macroglobulinemia (WM) is a rare, indolent B-cell lymphoma that predominantly affects older adults. In recent years, significant progress has been made in understanding its pathogenesis, identifying relevant biomarkers, and developing novel therapeutic approaches to complement traditional chemoimmunotherapy-collectively reshaping the management landscape of WM. In this article, we provide comprehensive, evidence-based recommendations for the diagnosis, molecular evaluation, and treatment of WM, including strategies for both frontline and relapsed disease. These guidelines are informed by the latest clinical research, expert consensus, and current practice standards, with the goal of equipping clinicians with a practical and effective framework for delivering optimal care to patients with WM.

It has been five years since the last version of the clinical practice guidelines for the management of adult diffuse gliomas was published by the Asian Glioma Genome Atlas (AGGA). Significant progress and revisions have occurred in the diagnosis and treatment of adult diffuse gliomas in recent years. In response to these updates, the joint guideline committee of the Chinese Glioma Cooperative Group (CGCG), the Society for Neuro-Oncology of China (SNO-China), and the Chinese Brain Cancer Association (CBCA) has revised the clinical practice guidelines. This updated guideline emphasizes molecular and pathological diagnostics, as well as the primary treatment modalities of surgery, radiotherapy, chemotherapy, and targeted therapy. Additionally, we have incorporated findings from recent clinical trials of new therapies to align with cutting-edge treatment strategies. This guideline is designed to serve as a practical resource for all professionals involved in managing adult diffuse glioma patients, while also providing valuable information for insurance companies and other institutions responsible for regulating cancer care costs in China and beyond.

Approximately 5% of all colorectal cancers have a strong genetic component and are classified as hereditary colorectal cancer (HCRC). Some of the unique features commonly seen in HCRC cases include early age of onset, synchronous/metachronous cancer occurrence, and multiple cancers in other organs. These characteristics require different management approaches, including diagnosis, treatment or surveillance, from those used in the management of sporadic colorectal cancer. Accurate diagnosis of HCRC is essential because it enables targeted surveillance and risk reduction strategies that improve patient outcomes. Recent genetic advances revealed several causative genes for polyposis and non-polyposis syndromes. The Japanese Society for Cancer of the Colon and Rectum (JSCCR) first published guidelines for the management of HCRC in 2012, with subsequent revisions every 4 years. The 2024 update to the JSCCR guidelines for HCRC was developed by meticulously reviewing evidence from systematic reviews and the consensus of the JSCCR HCRC Guidelines Committee, which includes representatives from patient advocacy groups for FAP and Lynch syndrome. These guidelines provide an up-to-date summary of HCRC, along with clinical recommendations for managing FAP and Lynch syndrome.

RAD51C, RAD51D, and BRIP1 germline pathogenic variants (GPVs) are associated with increased lifetime risks of tubo-ovarian cancer. Resources for managing RAD51C, RAD51D, and BRIP1 heterozygotes in clinical practice are limited.

To formulate standardized recommendations for recognizing and managing the genetic risk of breast cancer, based on the latest scientific evidence and clinical experience.

Over the years since the 4th Breast Cancer Consensus Conference, a substantial body of new evidence based on clinical trial results has been published, necessitating an update of the 2020 recommendations. This professional guideline primarily reflects the current ESMO, NCCN, ABC, and St. Gallen Consensus Conference statements and recommendations. From a didactic perspective, the text first addresses early-stage breast cancer, followed by locally advanced, locoregionally recurrent, and metastatic breast cancer. At the beginning of both the early-stage and metastatic breast cancer sections, we provide a summary of general principles relevant to the respective field, which apply to the subsequent subsections. Within these subsections, therapeutic options are discussed according to genomic subgroups. At the end of the recommendations, considerations for the management of certain rare clinical scenarios are summarized. The appendices cover, among other topics, multidisciplinary team (tumor board) requirements, recommended chemotherapy protocols, and the definition of menopause.

The Italian Society of Pathology's Molecular Pathology and Precision Medicine Study Group (PMMP/SIAPeC) has released a three-part set of best practice guidelines to stan-dardize and enhance molecular testing in solid tumors. Part I focuses on the pre-analytical phase, emphasizing proper tissue handling and quality control to preserve nucleic acid integrity. Part II addresses the analytical phase, outlining workflows for next-generation sequencing (NGS), from extraction to variant interpretation, with recommendations on choice of platform, gene panels, and bioinformatics. Part III covers the post-analytical phase, offering guidance on structured, clinically meaningful reporting to support thera-peutic decisions, including standards for both tissue and liquid biopsies. Together, these documents aim to harmonize molecular diagnostics, ensuring reliable, high-quality results that support precision oncology.

Molecular biologists play an important role in therapeutic decisions in the context of Chronic Myelogenous Leukemia (CML). Before treatment, it is mandatory to identify the BCR::ABL1 fusion and any prognostic cytogenetic abnormalities that may be present. During treatment, regular assessment of measurable residual disease (MRD) is essential to objectively evaluate the optimal response and identify situations of resistance to treatment. Monitoring of MRD is also required when considering treatment discontinuations. In cases of resistance, identifying mutations that confer resistance to tyrosine kinase inhibitors is essential for adapting the treatment. The Group of Molecular Biologists of Hematologic Malignancies (GBMHM) and the France Intergroup of Chronic Myeloid Leukemia (Fi-LMC) convened a panel of experts to critically review methods used for molecular diagnostics and follow-up of patients with CML, define best practices applicable in this context and formulate recommendations.

UK Guidelines for the management of uveal melanoma (UM) were first published in 2015 using an evidence-based systematic approach. The primary aim of this guideline was to optimise patient care by providing recommendations based on the best available scientific evidence. The resulting guideline reflected the strengths and weaknesses of the available evidence, made recommendations that were clinically impactful around prognostication, surveillance, and treatment for patients with primary lesions and metastatic disease. The guideline development process and content met the standards required by NICE and were ultimately NICE accredited. Here, we present an update to these guidelines, highlighting where practice or treatment has changed to such an extent that the original recommendations are now out of date. Presented here are updated guidelines on molecular and genetic testing, management of metastatic disease and clinical surveillance.

Microsatellite instability (MSI) is the accumulation of insertion and deletion variants (instability) in short tandem repeat DNA sequences (microsatellites). High levels of MSI occur following loss of function of the DNA mismatch repair system (MMR). MMR deficiency is an increasingly important cancer biomarker that is associated with chemotherapy resistance and response to immune checkpoint blockade, as well as one of the commonest hereditary cancer syndromes, Lynch syndrome. Since its discovery over two decades ago, our biological understanding, the testing methods, and the clinical implications of MSI analysis have expanded rapidly and up-to-date best practice guidelines are needed. An expert working group reviewed the literature and devised 15 best practice recommendations that were finalised following consultation with clinical and laboratory scientists partnered with EMQN. These include seven recommendations on key technical aspects of MSI testing and eight recommendations on the clinical interpretation and reporting of results. The latter focuses on Lynch syndrome screening and immune checkpoint blockade therapy. Example report wording is provided to assist implementation and standardisation. Common terminology and MSI analysis methods are also discussed. These guidelines are aimed primarily at genomic scientists working in diagnostic testing laboratories, but will provide a useful review of MSI for clinicians, academics, and other related professionals.

Uveal melanoma (UM) is a rare malignancy originating from uveal melanocytes. Despite effective control of the primary tumour, metastatic uveal melanoma (MUM) occurs in approximately 20-30% of patients, primarily affecting the liver, with a poor prognosis and overall survival (OS). The unique molecular profile of UM, lacking BRAF, NRAS, and KIT mutations, limits targeted therapy efficacy. Chemotherapy and immune checkpoint inhibitors (ICIs) also show limited benefits, while tebentafusp has emerged as the first drug to improve OS, but this systemic treatment can be used only in HLA-A*02:01-positive patients. A French multidisciplinary panel developed evidence-based guidelines for MUM management presented in this review. Recommendations emphasise on comprehensive diagnosis, including liver biopsy and imaging, circulating tumour DNA (ctDNA) analysis, and high-definition HLA typing for HLA-A*02:01. Local therapies are proposed for patients with limited hepatic metastases, from liver surgery to isolated hepatic perfusion and chemoembolisation for patients with more extensive hepatic involvement. Systemic therapy with tebentafusp is the standard of care for HLA-A*02:01-positive patients. For HLA-A*02:01-negative patients with extensive disease, treatment options are limited. They are encouraged to participate in a clinical trial, alternatively, percutaneous hepatic perfusion, ICI alone or in combination can be proposed. Treatment efficacy assessment includes response evaluation criteria in solid tumours (RECIST), tumour growth rate (TGR) analysis, and ctDNA dynamics. This consensus provides practical guidelines for French oncologists to optimise MUM management, integrating locoregional interventions, systemic therapies, and biomarkers to enhance patient outcomes.

With widening therapeutic indications, germline genetic testing is offered to an increasing proportion of patients with breast cancer (BC) via mainstream oncology services. However, the gene set tested varies widely from just BRCA1/BRCA2 through to 'pan-cancer' panels of nearly 100 genes. If a germline pathogenic variant (GPV) is detected, the BC proband and other family GPV-carriers may be offered interventions such as risk-reducing surgery and intensive surveillance over decades for the various cancers linked to that gene.

Constitutional or germline pathogenic variants (GPVs) in protection of telomeres 1 (POT1) are associated with a variety of tumours resulting in the recognition of POT1-tumour predisposition syndrome (POT1-TPDS). These tumours may include cutaneous melanoma, angiosarcoma, haematological malignancy and brain tumours. Due to the rarity of POT1 GPVs and limited available data, the overall lifetime cancer risks for individuals with POT1-TPDS are unclear. Furthermore, there is scant evidence to support the role of surveillance in early cancer detection in this patient group. A recent international publication suggested a surveillance protocol similar to that used in Li-Fraumeni Syndrome (LFS) could be offered to POT1 pathogenic variant carriers, particularly where there are LFS-like features. However, current evidence for POT1-TPDS is not supportive of an equivalent lifetime cancer risk. Given the inclusion of POT1 in the National Test Directory in England and the need for UK-based guidance, an expert group undertook a literature review to assess the phenotypic spectrum of POT1-TPDS and to provide lifetime risk estimates of POT1-associated cancers. The available evidence was shared with a small working group of experts that included clinical geneticists, dermatologists, sarcoma specialists, haematologists and radiologists to cover all aspects of the cancers most commonly associated with POT1-TPDS. Following structured expert group discussions, we achieved consensus on best practice recommendations for a POT1-TPDS UK management protocol.

Anaplastic thyroid cancer is a rare and rapidly deadly disease. In case of clinical suspicion (rapid growth, stony neck mass), diagnostic work-up should be carried out as a matter of urgency to enable prompt treatment. Multidisciplinary assessment involving the patient's referring specialists, the support care team, and if necessary, a geriatric oncology specialist should be performed and must take account of disease extent, comorbidities, general health status and the patient's wishes. Patients and their families should receive realistic information about the prognosis; either active treatment in parallel to support care or exclusive palliative care can be recommended from the outset. Despite the dismal prognosis, recent advances in tumor molecular profiling and treatment with the advent of targeted treatment and immunotherapy hold out great promise for the future. This article summarizes the consensus recommendations on management of anaplastic thyroid cancers by the ENDOCAN TUTHYREF network, a rare-cancer network of the French National Institute for Cancer (INCa).

Radioactive-iodine-refractory differentiated thyroid cancer (RAIR DTC) represents 3-5% of follicular-derived DTCs, with approximately 200-300 new cases diagnosed annually in France. Median overall survival in the French RAIR DTC database is 9.5years, underscoring the importance of long-term support for caregivers and patients. To guide treatment decision-making, the French ENDOCAN TUTHYREF network has provided algorithms for RAIR DTC management, available at the TUTHYREF website. The present article summarizes these recent practical recommendations, focusing on 5 points. (1) RAIR DTC has long been defined by locally advanced disease not amenable to surgery or metastatic disease not fully responding to radioactive iodine (RAI) therapy, a definition that can be further refined considering prognostic factors. (2) Treatment should be tailored according to tumor burden and progression, with local treatments prioritized for non-progressive or slowly progressive disease. (3) Early tumor molecular testing should be performed to identify driver oncogenes such as BRAF mutation or RET/NTRK/ALK fusion, to optimize access to existing selective targeted therapies. (4) For symptomatic or progressive RAIR DTC, tyrosine multikinase inhibitors, such as sorafenib, lenvatinib or cabozantinib, are the standard therapies, but alternative and 2nd-line kinase inhibitors are also available. (5) Since most therapies are associated with common side-effects such as fatigue and cardiovascular, digestive and skin issues, preparing and monitoring patients for systemic therapy should include careful assessment of comorbidities, toxicity prevention and individual dose adjustment. Overall, management of RAIR DTC requires a multidisciplinary approach, with an emphasis on personalized treatment strategies and proactive therapeutic education.

Medullary thyroid carcinoma (MTC) accounts for 2-4% of thyroid cancers. It has the particularity of being a neuroendocrine tumor associated with a proto-oncogene germline RET mutation: germline in 20-25% of cases, somatic in 70-80% of metastatic sporadic cases. Locally advanced and metastatic MTCs are called "refractory". Individual prognosis is difficult, since the clinical behavior of the disease varies greatly from one patient to another. However, histological factors, such as high-grade forms, associated with greater risk of tumor progression and death, have been recently identified, and biological factors, such as the doubling time of plasma calcitonin, may help assess prognosis. Treatment of refractory medullary thyroid carcinoma has progressed considerably over recent years, with the advent of targeted therapies such as multi-kinase inhibitors and selective RET inhibitors. Management requires multidisciplinary expertise, and is tailored to the individual clinical situation patient, the molecular characteristics of the tumor, and the progression of the disease. These advances have led the ENDOCAN-TUTHYREF rare-cancer network of the French National Institute for Cancer (INCa), dedicated to refractory thyroid cancer, to draw up a set of consensus recommendations. This article focuses on refractory medullary thyroid cancer.

With an increased uptake of genomic profiling in clinical practice and the evolving complexity of diagnostic modalities, vast amounts of complex data need to be properly interpreted and integrated into an individualised care plan. To address these challenges, molecular tumour boards (MTBs) have been widely established. As of today, no international recommendations regulating the composition and workflows of MTBs have been defined.