Trifluridine/tipiracil is currently approved for metastatic colorectal cancer (mCRC) refractory to available therapies. However, there is no consensus on factors that predict treatment outcomes in daily practice. We assessed the early clinical experience with trifluridine/tipiracil in Spain and potential survival markers. This was a retrospective cohort study of mCRC patients who participated in the trifluridine/tipiracil early clinical experience programme in Spain. The primary outcome was overall survival (OS). Associations between OS and patient characteristics were assessed using multivariate Cox regression analyses. A total of 379 patients were included in the study. Trifluridine/tipiracil was administered for a median of 3.0 cycles and discontinued mainly due to disease progression (79.2%). The median OS was 7.9 months, with a 12-month OS rate of 30.5%. Cox analyses revealed that the following variables independently enhanced OS: ≤2 metastatic sites, no liver metastasis, alkaline phosphatase < 300 IU, trifluridine/tipiracil dose reductions, and neutrophil/lymphocyte ratio < 5. Grade ≥ 3 toxicities were reported in 141 (37.2%) patients, including mainly afebrile neutropaenia (23.2%), anaemia (12.1%), and thrombocytopaenia (5.3%). This study supports the real-life efficacy and safety of trifluridine/tipiracil for refractory mCRC and identifies tumour burden, liver metastasis, alkaline phosphatase, dose reductions, and neutrophil/lymphocyte ratio as survival markers.

Mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs) are a heterogeneous group of malignant neoplasms that can settle in the gastroenteropancreatic tract. They are composed of a neuroendocrine (NE) and a non-NE component in at least 30% of each tumour. The non-NE component can include different histological combinations of glandular, squamous, mucinous and sarcomatoid phenotypes, and one or both of the components can be low-or high grade malignant. Recent changes in the nomenclature of these neoplasms might lead to great deal of confusion, and the lack of specific clinical trials is the main reason why their management is difficult. The review aims to clarify the definition of MiNEN and analyze available evidence about their diagnosis and treatment options according to their location and extension through careful analysis of the available data. It would be important to reach a general consensus on their diagnosis in order to construct a classification that remains stable over time and facilitates the design of clinical trials that, due to their low incidence, will require long recruitment periods.

Anal cancer is rare but increasingly common, currently accounting for 2% of all digestive neoplasms. Some 50% of anal cancers are diagnosed at the localized stage, 29% as locoregional disease, and 12% as metastatic disease. When clinical suspicion of anal cancer exists, histological confirmation, correct local staging with MRI and distant staging with thoraco-abdominal CT, and management by a multidisciplinary team are mandatory. Chemoradiotherapy with 5-FU and mitomycin C (MMC) is the standard of care for early and locally advanced disease, while combination chemotherapy with a platinum-containing compound and taxanes is the treatment of choice for metastatic disease.