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Transarterial radioembolization (TARE) with yttrium-90 (Y90) is a promising alternative strategy to treat liver tumors and liver metastasis from colorectal cancer (CRC), as it selectively delivers radioactive isotopes to the tumor via the hepatic artery, sparring surrounding liver tissue. The landscape of TARE indications is constantly evolving. This strategy is considered for patients with hepatocellular carcinoma (HCC) with liver-confined disease and preserved liver function in whom neither TACE nor systemic therapy is possible. In patients with liver metastases from CRC, TARE is advised when other chemotherapeutic options have failed. Recent phase III trials have not succeeded to prove benefit in overall survival; however, it has helped to better understand the patients that may benefit from TARE based on subgroup analysis. New strategies and treatment combinations are being investigated in ongoing clinical trials. The aim of this review is to summarize the clinical applications of TARE in patients with gastrointestinal malignancies., (© 2021. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

Introduction: Approximately 10% of pediatric patients with cancer have an inherited, sometimes masked, cancer predisposition syndrome (CPS). Identifying patients with genetic susceptibility to malignant disease is essential for their correct diagnosis and clinical management., Materials and Methods: Here, we present the workflow and experience of a multidisciplinary cancer predisposition unit focused on pediatric patients with cancer., Results: Between July 2018 and July 2020, 214 patients were diagnosed with pediatric cancer in our Hospital. Of all, 49 patients were treated at the CPS unit, 48 of whom were recommended a genetic study. Mutational analysis was performed on DNA from peripheral blood samples, with approximately 45% of the patients (n = 22) receiving a confirmed CPS diagnosis, all of whom underwent genetic counseling. These cases represent 20% of all pediatric cancers diagnosed in the same center during this period. Most of the patients were diagnosed with hereditary retinoblastoma; however, we also identified families with Li-Fraumeni syndrome, multiple endocrine neoplasia type 2, hereditary melanoma, hereditary leiomyomatosis, and Gardner syndrome., Conclusion: Despite its limitations regarding the type of tumors and number of patients included, this study revealed that implementing a specialized unit focused on children with cancer results in a higher diagnostic rate and better genetic counseling for patients with pediatric cancer predisposition syndromes., (© 2022. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Background: Merkel cell carcinoma (MCC) is a malignant skin cancer with a 5-year survival rate of approximately 50%. Knowledge of MCC has increased in recent years mostly due to improved diagnosis techniques. In Spain there is lack of information regarding the incidence and tumour characteristics, and the treatment approaches are not standardised. The objective of this study was to provide information of the clinical and epidemiological characteristics of MCC patients in Spain., Methods: Retrospective, observational study involving 192 patients from 25 Spanish hospitals. Evaluated variables included overall survival and incidence rate of Merkel cell polyomavirus, in patients diagnosed from 2012 to 2016., Results: The Spanish incidence rate was estimated 0.32/100,000 inhabitants/year, with variations according to geographical regions, being slightly higher in areas with greater sunlight exposure. In total, 61.5% of tumours showed expansive growth (progressive growth of the tumour), 78.6% showed localisation in UV-exposed skin. 97.4% of patients were diagnosed by excisional biopsy. Surgery was the first line treatment in 96.6% of patients, radiotherapy in 24.6%, and chemotherapy in 6.3%. These treatments were not mutually exclusive. Median overall survival was 38.3 months (78.4% at 12 months and 60% at 24 months). MCPyV was present in 33.8% of patients., Conclusion: The incidence of MCC in Spain is one of the highest in Europe, with a slight predominance in men. The sample has shown that a biopsy is available for diagnosis in most cases. Moreover, the treatment is surgical when the tumour is localized and is associated with lymphadenectomy, and/or it is radiotherapy if widespread., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Neurofibromatosis type 1 (NF1) is a genetic disorder that carries a higher risk of tumor development. Plexiform neurofibromas (PNs) are present in 50% of NF1 and cause significant morbidity when surgery is not feasible. Systemic therapies had not succeeded to reduce PN tumor volume until 2016 when the first trial with an MAPK/extracellular-signal-regulated kinase (MEK) inhibitor was published. We performed a systematic research on novel targeted therapies for patients with NF1 and PNs in PubMed, EMBASE, and conference abstracts with the last update in February 2021. Since 2016, seven trials have reported positive results with MEK inhibitors and other molecular targeted therapies (cabozantinib). Selumetinib has shown an overall response rate of 68% in children with NF1 and symptomatic inoperable PNs, and was associated with pain improvement and a manageable adverse events profile. This led to Food and Drug Administration (FDA) approval of selumetinib in May 2020. Recently, cabozantinib and mirdametinib have also proven their efficacy in adult population. Other MEK inhibitors such as trametinib and binimetinib have also communicated promising preliminary results. Ongoing trials in different populations and with intermittent dosing strategies are underway., Competing Interests: Disclosure The authors have declared no conflicts of interest., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The prognostic value of neutrophil-to-lymphocyte ratio (NLR) has been extensively studied in cancer patients. However, the performance of NLR as an early marker of efficacy of immune checkpoint inhibitors (ICI) is still understudied. We studied the utility of NLR at baseline (bNLR), before the second dose of immunotherapy (NLR2) and the NLR trend for predicting efficacy outcomes., Methods: We included all patients with advanced cancer treated with ICI from June 2013 to April 2019 at La Paz University Hospital, Madrid (Spain). We examined bNLR, NLR2 and NLR trend and explored the association with progression-free survival (PFS) at 6 months, median PFS and overall survival (OS)., Results: We included 211 patients. PFS and OS were significantly longer in the low bNLR group than in the high bNLR group [HR 0.71 (95% CI 0.60-0.84) and HR: 0.66 (95% CI 0.55-0.79), respectively]. Regarding NLR2, patients with low NLR2 had significantly longer PFS and OS than patients with high NLR2 [HR 0.67 (95% CI 0.57-0.79) and HR: 0.60 (95% CI 0.50-0.72), respectively]. Finally, for NLR trend, PFS and OS for patients with NLR trend < 1 were significantly longer than those patients with NLR trend ≥ 1 [HR 0.59 (95% CI 0.43-0.82) and HR 0.63 (95% CI 0.44-0.90), respectively]. At the multivariate analysis for PFS and OS, bNLR, NLR2 and NLR trend were all independent prognostic factors for PFS and OS., Conclusions: bNLR, NLR2 and NLR trends are independent prognostic factors for survival in patients on immunotherapy. The dynamics of NLR in patients on immunotherapy is a promising marker that needs further investigation.

Background: Capectiabine is an oral antineoplastic drug used in multiple malignancies. Proton pump inhibitors (PPI) have been proven to interact with other oral antineoplastic agents. In this systematic review we will summarize the clinical evidence on the efficacy of capecitabine when used concomitantly with PPI., Materials and Methods: We performed a systematic literature search on the main databases up to November 2019., Results: Nine studies met our inclusion criteria: 8 retrospective studies and 1 phase II clinical trial. Patients with colorectal, breast and gastroesophageal were represented. Four out of the 9 studies reported a shorter efficacy outcome in uni- or multivariate analysis when capecitabine was taken concomitantly with PPI than alone., Conclusions: Up to date, the clinical evidence reported on the use of capecitabine concomitantly with PPI is scarce and shows conflicting results. While awaiting further data, avoiding misuse of PPI in cancer patients taking capecitabine is recommended.

Background: Oxaliplatin is a chemotherapy agent active against digestive tumors. Peripheral neuropathy is one of the most important dose-limiting toxicity of this drug. It occurs in around 60-80% of the patients, and 15% of them develop severe neuropathy. The pathophysiology of oxaliplatin neurotoxicity remains unclear. SCN9A is a gene codifying for a subtype sodium channel (type IX, subunit α) and mutations in this gene are involved in neuropathic perception. In this study we investigated whether SCN9A genetic variants were associated with risk of neurotoxicity in patients diagnosed of cancer on treatment with oxaliplatin., Methods: Blood samples from 94 patients diagnosed of digestive cancer that had received oxaliplatin in adjuvant or metastatic setting were obtained from three hospitals in Madrid. These patients were classified into two groups: "cases" developed oxaliplatin-induced grade 3-4 neuropathy (n = 48), and "controls" (n = 46) had no neuropathy or grade 1. The neuropathy was evaluated by an expert neurologist and included a clinical examination and classification according to validated neurological scales: National Cancer Institute Common Toxicity Criteria (NCI-CTC), Oxaliplatin-Specific Neurotoxicity Scale (OSNS) and Total Neuropathy score (TNS). Genotyping was performed for 3 SCN9A missense polymorphisms: rs6746030 (R1150W), rs74401238 (R1110Q) and rs41268673 (P610T), and associations between genotypes and neuropathy were evaluated., Results: We found that SCN9A rs6746030 was associated with protection for severe neuropathy (OR = 0.39, 95% CI = 0.16-0.96; p = 0.041). Multivariate analysis adjusting for diabetes provided similar results (p = 0.036). No significant differences in neuropathy risk were detected for rs74401238 and rs41268673., Conclusion: SCN9A rs6746030 was associated with protection for severe oxaliplatin-induced peripheral neuropathy. The validation of this exploratory study is ongoing in an independent series.

Colorectal cancer (CRC) is characterized by alteration of critical pathways such TP53 inactivation, BRAF, PI3CA mutations, APC inactivation, KRAS, TGF-β, CTNNB mutations, disregulation of Epithelial to mesnechymal transition (EMT) genes, WNT signaling activation, MYC amplification, and others. Differences in these molecular events results in differences in phenotypic characteristics of CRC, that have been studied and classified by different models of molecular subtypes. It could have potential applications to prognosis, but also to therapeutical approaches of the CRC patients. We review and summarized the different molecular classifications and try to clarify their clinical and therapeutical relevance., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Hepatocellular carcinoma (HCC) represents the second leading cause of cancer-related death worldwide. Surveillance with abdominal ultrasound every 6 months should be offered to patients with a high risk of developing HCC: Child-Pugh A-B cirrhotic patients, all cirrhotic patients on the waiting list for liver transplantation, high-risk HBV chronic hepatitis patients (higher viral load, viral genotype or Asian or African ancestry) and patients with chronic hepatitis C and bridging fibrosis. Accurate diagnosis, staging and functional hepatic reserve are crucial for the optimal therapeutic approach. Characteristic findings on dynamic CT/MR of arterial hyperenhancement with "washout" in the portal venous or delayed phase are highly specific and sensitive for a diagnosis of HCC in patients with previous cirrhosis, but a confirmed histopathologic diagnosis should be done in patients without previous evidence of chronic hepatic disease. BCLC classification is the most common staging system used in Western countries. Surgical procedures, local therapies and systemic treatments should be discussed and planned for each patient by a multidisciplinary team according to the stage, performance status, liver function and comorbidities. Surgical interventions remain as the only curative procedures but both local and systemic approaches may increase survival and should be offered to patients without contraindications.