Multidisciplinary practice guidelines for the diagnosis, genetic counseling and treatment of pheochromocytomas and paragangliomas.

Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors that arise from chromaffin cells of the adrenal medulla and the sympathetic/parasympathetic neural ganglia, respectively. The heterogeneity in its etiology makes PPGL diagnosis and treatment very complex. The aim of this article was to provide practical clinical guidelines for the diagnosis and treatment of PPGLs from a multidisciplinary perspective, with the involvement of the Spanish Societies of Endocrinology and Nutrition (SEEN), Medical Oncology (SEOM), Medical Radiology (SERAM), Nuclear Medicine and Molecular Imaging (SEMNIM), Otorhinolaryngology (SEORL), Pathology (SEAP), Radiation Oncology (SEOR), Surgery (AEC) and the Spanish National Cancer Research Center (CNIO). We will review the following topics: epidemiology; anatomy, pathology and molecular pathways; clinical presentation; hereditary predisposition syndromes and genetic counseling and testing; diagnostic procedures, including biochemical testing and imaging studies; treatment including catecholamine blockade, surgery, radiotherapy and radiometabolic therapy, systemic therapy, local ablative therapy and supportive care. Finally, we will provide follow-up recommendations.

SEOM clinical guidelines for pancreatic and biliary tract cancer (2020).

Pancreatic cancer (PC) and biliary tract cancer (BTC) are both aggressive and highly fatal malignancies. Nowadays we have a profound knowledge about the molecular landscape of these neoplasms and this has allowed new therapeutic options. Surgery is the only potentially curative therapy in both cancers, but disease recurrence is frequent. In PC, adjuvant treatment with mFOLFIRINOX has improved overall survival (OS) and in BTC adjuvant treatment with capecitabine seems to improve OS and relapse-free survival. Concomitant radio-chemotherapy could also be considered following R1 surgery in both neoplasms. Neoadjuvant treatment represents the best option for achieving an R0 resection in borderline PC. Upfront systemic chemotherapy is the treatment of choice in unresectable locally advanced PC and BTC; then locoregional therapy could be considered after an initial period of at least 3-4 months of systemic chemotherapy. In metastatic PC, FOLFIRINOX or Gemcitabine plus nab-paclitaxel have improved OS compared with gemcitabine alone. In metastatic BTC, cisplatin plus gemcitabine constitute the standard treatment. Progress in the knowledge of molecular biology has enabled the identification of new targets for therapy with encouraging results that could in the future improve the survival and quality of life of patients with PC and BTC.

Update of the recommendations for the determination of biomarkers in colorectal carcinoma: National Consensus of the Spanish Society of Medical Oncology and the Spanish Society of Pathology.

In this update of the consensus of the Spanish Society of Medical Oncology (Sociedad Española de Oncología Médica-SEOM) and the Spanish Society of Pathology (Sociedad Española de Anatomía Patológica-SEAP), advances in the analysis of biomarkers in advanced colorectal cancer (CRC) as well as susceptibility markers of hereditary CRC and molecular biomarkers of localized CRC are reviewed. Recently published information on the essential determination of KRAS, NRAS and BRAF mutations and the convenience of determining the amplification of human epidermal growth factor receptor 2 (HER2), the expression of proteins in the DNA repair pathway and the study of NTRK fusions are also evaluated. From the pathological point of view, the importance of analysing the tumour budding and poorly differentiated clusters, and its prognostic value in CRC is reviewed, as well as the impact of molecular lymph node analysis on lymph node staging in CRC. The incorporation of pan-genomic technologies, such as next-generation sequencing (NGS) and liquid biopsy in the clinical management of patients with CRC is also outlined. All these aspects are developed in this guide, which, like the previous one, will remain open to any necessary revision in the future.

SEOM clinical guidelines for the diagnosis and treatment of gastroenteropancreatic and bronchial neuroendocrine neoplasms (NENs) (2018).

NENs are a heterogeneous family of tumors of challenging diagnosis and clinical management. Their incidence and prevalence continue to rise across all sites, stages and grades. Although improved diagnostic techniques have led to earlier detection and stage migration, the improved prognosis documented over time for advanced gastrointestinal and pancreatic neuroendocrine tumors also reflect improvements in therapy. The aim of this guideline is to update practical recommendations for the diagnosis and treatment of gastroenteropancreatic and lung NENs. Diagnostic procedures, histological classification and therapeutic options are briefly discussed, including surgery, liver-directed therapy, peptide receptor radionuclide therapy, and systemic hormonal, cytotoxic or targeted therapy, and treatment algorithms are provided.

Efficacy of trifluridine and tipiracil (TAS-102) versus placebo, with supportive care, in a randomized, controlled trial of patients with metastatic colorectal cancer from Spain: results of a subgroup analysis of the phase 3 RECOURSE trial.

PURPOSE: TAS-102 is a combination of the thymidine-based nucleoside analog trifluridine and the thymidine phosphorylase inhibitor tipiracil. Efficacy and safety of TAS-102 in patients with metastatic colorectal cancer (mCRC) refractory or intolerant to standard therapies were evaluated in the phase 3 RECOURSE trial. Results of RECOURSE demonstrated significant improvement in overall survival (OS) and progression-free survival (PFS) with TAS-102 versus placebo [hazard ratio (HR) = 0.68 and 0.48 for OS and PFS, respectively; both P < 0.001]. The current analysis evaluates efficacy and safety of TAS-102 in the RECOURSE Spanish subgroup. METHODS: Primary and key secondary endpoints were evaluated in a post hoc analysis of the RECOURSE Spanish subgroup, using univariate and multivariate analyses. Safety and tolerability were reported with descriptive statistics. RESULTS: The RECOURSE Spanish subgroup included 112 patients (mean age 61 years, 62 % male). Median OS was 6.8 months in the TAS-102 group (n = 80) versus 4.6 months in the placebo group (n = 32) [HR = 0.47; 95 % confidence interval (CI): 0.28-0.78; P = 0.0032). Median PFS was 2.0 months in the TAS-102 group and 1.7 months in the placebo group (HR = 0.47; 95 % CI: 0.30-0.74; P = 0.001). Eighty (100 %) TAS-102 versus 31 (96.9 %) placebo patients had adverse events (AEs). The most common drug-related ≥Grade 3 AE was neutropenia (40 % TAS-102 versus 0 % placebo). There was 1 (1.3 %) case of febrile neutropenia in the TAS-102 group versus none in the placebo group. CONCLUSIONS: In the RECOURSE Spanish subgroup, TAS-102 was associated with significantly improved OS and PFS versus placebo, consistent with the overall RECOURSE population. No new safety signals were identified. CLINICALTRIALS. GOV STUDY NUMBER: NCT01607957.

SEOM/SERAM consensus statement on radiological diagnosis, response assessment and follow-up in colorectal cancer.

Colorectal cancer (CRC) is one of the world's most common cancers, and has one of the highest mortality rates. The last few decades have seen great progress in preventing, diagnosing and treating this disease, providing undeniable impact on patients' prognosis and quality of life. At all these stages of CRC management, imaging techniques play an essential role. This article reviews some important issues concerning the use of various radiological techniques in the screening, diagnosis, staging, assessment of treatment response, and follow-up of patients with CRC. It also includes a number of practical recommendations on indications for use, technical requirements, minimum information required in the radiology report, evaluation criteria for the response to various drugs, and the recommended frequency at which different examinations should be performed. This consensus statement is the result of cooperation between the Spanish Society of Medical Oncology (SEOM) and the Spanish Society of Radiology (SERAM).

Is regorafenib providing clinically meaningful benefits to pretreated patients with metastatic colorectal cancer?

Treatment with regorafenib has demonstrated statistically significant improvements in terms of overall survival, progression-free survival and disease control when compared with placebo in pretreated patients with metastatic colorectal cancer in two placebo-controlled, randomized, phase III trials (CORRECT and CONCUR). Similar results were observed in two open-label, single-arm studies (REBECCA and CONSIGN) performed in the real-world setting. But several authors have suggested that the benefit provided by regorafenib may not be clinically meaningful for these patients. Moreover, it has been suggested that not all subgroups of patients might benefit from regorafenib. The intention of this review is to provide an overview of the existing evidence for regorafenib in terms of efficacy, tolerability and quality of life in different subpopulations according to clinical and biological characteristics. Additionally, the magnitude of the clinical benefit provided by regorafenib to these patients has been explored and whether there are poorer outcomes in certain subpopulations.

SEOM clinical guidelines for diagnosis and treatment of metastatic colorectal cancer 2015.

Colorectal cancer (CRC) is the second leading cause of cancer dead in Spain. About half the patients will eventually develop distant metastases. However, as treatment options are expanding, prognosis has steadily improved over the last decades. Management of advanced CRC should be discussed within an experienced multidisciplinary team to select the most appropriate systemic treatment (chemotherapy and targeted agents) and to integrate surgical or ablative procedures when indicated. Disease site and extent, resectability, tumor biology and gene mutations, clinical presentation, patient preferences, and comorbidities are key factors to design a customized treatment plan. The aim of these guidelines is to provide synthetic recommendations for managing advanced CRC patients.

Updated guidelines for biomarker testing in colorectal carcinoma: a national consensus of the Spanish Society of Pathology and the Spanish Society of Medical Oncology.

Publication of this consensus statement is a joint initiative of the Spanish Society of Pathology (SEAP) and the Spanish Society of Medical Oncology (SEOM), intended to revise and update the diagnostic and treatment recommendations published 2 years ago on biomarker use and the management of patients with colorectal carcinoma (CRC), thereby providing an opportunity to improve healthcare efficiency and resource use in these patients. This expert group recommends testing for KRAS and NRAS status in all patients with metastatic CRC being considered for anti-epidermal growth factor receptor (anti-EGFR) therapy, as this type of treatment should only be used in patients not harbouring mutations in these genes. In contrast, testing for BRAF, EGFR, PI3K and PTEN mutation status is not necessary for therapeutic decision making, so does not need to be done routinely.

Clinical management of regorafenib in the treatment of patients with advanced colorectal cancer.

Colorectal cancer is one of the most common tumors worldwide and at least 50 % of patients with this disease develop metastases. In this setting, additional treatment options are needed for patients presenting disease progression after exhausting all standard therapies. Regorafenib is an orally administered multikinase inhibitor which has been shown to provide survival benefits to patients with metastatic colorectal cancer (mCRC). Although most adverse events (AEs) associated with regorafenib may resolve within the first 8 weeks of treatment, some of them may require dose reduction or treatment interruption. Overall, while remaining aware of the safety profile of regorafenib and how to manage the most common toxicities related to its use, this drug should be considered a new standard of care for patients with pretreated mCRC. This review addresses practical aspects of its use, such as dosing, patient monitoring, and management of the most common regorafenib-related AEs.

SEOM clinical guidelines for the diagnosis and treatment of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) 2014.

GEP-NENs are a challenging family of tumors of growing incidence and varied clinical management and behavior. Diagnostic techniques have substantially improved over the past decades and significant advances have been achieved in the understanding of the molecular pathways governing tumor initiation and progression. This has already translated into relevant advances in the clinic. This guideline aims to provide practical recommendations for the diagnosis and treatment of GEP-NENs. Diagnostic workup, histological and staging classifications, and the different available therapeutic approaches, including surgery, liver-directed ablative therapies, peptide receptor radionuclide therapy, and systemic hormonal, cytotoxic or targeted therapy, are briefly discussed in this manuscript. Clinical presentation (performance status, comorbidities, tumor-derived symptoms and hormone syndrome in functioning tumors), histological features [tumor differentiation, proliferation rate (Ki-67), and expression of somatostatin receptors], disease localization and extent, and resectability of primary and metastatic disease, are all key issues that shall be taken into consideration to appropriately tailor therapeutic strategies and surveillance of these patients.

Guidelines for biomarker testing in gastroenteropancreatic neuroendocrine neoplasms: a national consensus of the Spanish Society of Pathology and the Spanish Society of Medical Oncology.

The annual incidence of neuroendocrine tumours in the Caucasian population ranges from 2.5 to 5 new cases per 100,000 inhabitants. Gastroenteropancreatic neuroendocrine tumours is a family of neoplasms widely variable in terms of anatomical location, hormone composition, clinical syndromes they cause and in their biological behaviour. This high complexity and clinical heterogeneity, together with the known difficulty of predicting their behaviour from their pathological features, are reflected in the many classifications that have been developed over the years in this field. This article reviews the main tissue and clinical biomarkers and makes recommendations for their use in medical practice. This document represents a consensus reached jointly by the Spanish Society of Medical Oncology (SEOM) and the Spanish Society of Pathology (SEAP).

SEOM clinical guidelines for the treatment of advanced colorectal cancer 2013.

Colorectal cancer (CRC) is the most common malignant tumor in Western countries. Despite efforts made to implement screening programmes for early detection and treatment, still half of the patients present or will eventually develop distant metastasis. Management of advanced CRC should be discussed within an experienced multidisciplinary team, to adequately select the most appropriate systemic therapeutic option, as well as the optimal way to integrate it with surgical procedures when indicated. Disease localization and extent, resectability of primary and metastatic disease, tumor biology and dynamics, clinical symptoms, personal preferences and patient's ability to tolerate intensive chemotherapy or extensive surgical procedures are the key factors to properly design a customized treatment plan. The aim of the current manuscript is to provide synthetic practical guidelines regarding therapeutic options for advanced CRC.

Recommendations and expert opinion on the adjuvant treatment of colon cancer in Spain.

Adjuvant chemotherapy is the current standard in the management of patients with localised colon cancer (CC) following curative resection. The use of oxaliplatin plus 5 fluorouracil/leucovorin (FOLFOX) or oxaliplatin plus capecitabine-based (XELOX) regimens, both approved in Europe as adjuvant treatment for stage III CC, has improved prognosis in this stage, but questions on their usefulness in high-risk stage II or elderly CC patients and on the role of some prognostic biomarkers are still pending. In April 2010, a consensus meeting on adjuvant CC treatment based on a revision of the most recent literature was held in Spain. The panel considered the use of adjuvant chemotherapy for high-risk stage II CC patients to be justified. Additionally, the more convenient administration of oral fluoropyrimidines vs. IV continuous infusion 5-FU would make XELOX a more suitable alternative for the patient. A more cautious decision should be taken when prescribing oxaliplatin treatment in patients aged ≥70.

Phase I/II study of gefitinib and capecitabine in patients with colorectal cancer.

OBJECTIVE: The objectives of this phase I/II study were to determine the maximum tolerated dose (MTD), characterise the principal toxicities in the phase I part and assess the efficacy in the phase II part of gefitinib, an oral selective inhibitor of the epidermal growth factor receptor, in combination with capecitabine in patients with advanced colorectal cancer (CRC). METHODS AND PATIENTS: Patients with advanced CRC were treated with gefitinib administered daily for 21 days and capecitabine administered twice daily for 14 days of a 21-day cycle. The dose levels of gefitinib (mg) and capecitabine (mg/m(2) bid) assessed were 250/1000 and 250/ 1250. An expanded cohort was enrolled at the MTD to better characterise toxicity and efficacy. A total of 32 previously treated patients were accrued. In the phase I part 10 subjects were treated, with one dose-limiting toxicity. Overall 26 patients were treated at the MTD of the combination, which was gefitinib 250 mg/day and capecitabine 1250 mg/m(2) twice daily. RESULTS: The most frequent treatment-related adverse events included asthenia, diarrhoea, nausea, rash and anorexia. The incidence profile was very similar in phases I and II. No objective responses were documented but 53% of the patients achieved stable disease as best response to therapy. CONCLUSIONS: Capecitabine 1250 mg/m(2) twice daily 14 of 21 days and gefitinib at 250 mg/day can be safely administered in combination. The combination is relatively well tolerated. There were no objective responses, although an interesting stabilisation rate was documented, in previously treated advanced CRC patients.