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Importance of the field:Metastatic tumours of the liver are responsible for significant morbidity and mortality, and only a small percentage is resectable with curative intent. Hepatic artery radioembolization (RE) with yttrium-90 (90Y)-loaded microspheres is an alternative treatment for patients with unresectable primary or secondary liver tumours, especially in cases of metastatic colorectal cancer (mCRC) and hepatocellular carcinoma (HCC).Areas covered in this review:Data from recent relevant clinical trials with 90Y-RE are discussed, focusing on response rate assessments and treatment outcome.What the reader will gain:Current data show that 90Y-RE combined with radiosensitizing chemotherapy is a safe and efficient modality that extends the time to progression in liver mCRC and unresectable HCC, although no survival benefits have been demonstrated. The treatment response after 90Y-RE seems to be better assessed using metabolic response assessments with serial fluorodeoxyglucose positron emission tomography (FDG-PET) in cases of FDG-avid tumours than with morphological criteria measured on computed tomography or magnetic resonance imaging (RECIST or WHO trials). Predictive models using multimodality imaging approaches (PET-SPECT-CT image fusion algorithms) have been proposed to better select patients for 90Y-RE. The optimal routine role of radioembolization remains to be defined; the complexity and wide availability of available therapeutic alternatives confuses the role of a locoregional treatment in a generalized disease.Take home message:90Y-RE is a safe and efficient treatment modality in salvage therapy of colorectal cancer metastatic to the liver and in unresectable HCC. However, it has still to find its place as a first- or second-line treatment of mCRC in combination with or as an alternative to available biological agents. The role of 90Y-RE in other solid tumour types metastatic to the liver is much more uncertain and investigations in clinical situations in which disease is strictly limited to the liver are required. Pretherapeutic work-up, initially developed to explore hepatic vasculature and to assess lung shunting, might be able to predict treatment outcome, allowing a better patient selection.

Liver metastases from colorectal cancer (CRC) have a poor prognosis. Despite recent advances in the management of advanced disease with chemotherapy, liver resection remains the only hope for cure for patients with colorectal liver metastases. Approximately 15 of patients with stage IV CRC referred to specialist centers have metastatic liver disease deemed to be resectable at presentation. Over the last five years, combination chemotherapeutic regimens, namely 5-fluorouracil/folinic acid with irinotecan or oxaliplatin and, more recently, integrating targeted monoclonal antibodies, have been shown to downsize the tumour burden to an extent that sometimes allows initially unresectable metastases to be excised. Five-year survival rates following liver resection range between 25 and 55 compared with 0 and 5 for non-operated patients. Beyond liver resection, the rationale for “pseudo-adjuvant” chemotherapy lacks scientific evidence, despite some promising data. However, perioperative chemotherapy for resectable lesions is gaining ground in current practice. In this article we review the state of the art treatment for CRC liver metastases and, considering the results of recent trials, try to determine the appropriate role of chemotherapy.

Gemcitabine is the backbone therapy of patients with advanced pancreatic cancer. Its tolerability and efficacy remain poorly studied in elderly.

Despite staining positive for the epidermal growth factor receptor (EGFR), a significant number of EGFR-expressing colorectal cancers are resistant to cetuximab, a chimeric monoclonal antibody directed against EGFR. Activation of EGFR through the autophosphorylation of its tyrosine residues stimulates different signaling downstream pathways and may reflect the level of receptor utilization by the tumor. This study investigated activated/phosphorylated EGFR (pEGFR) in 23 patients with EGFR-positive metastatic colorectal cancer refractory to irinotecan and treated with cetuximab, alone or in combination with irinotecan. Seven patients received cetuximab, and 16 patients received cetuximab plus irinotecan. Among the 23 patients, six (26%) had a partial response, 10 (44%) had stable disease, and seven (30%) had progressive disease. Median duration of disease control (partial response + stable disease) was 6 months. Nineteen out of 20 EGFR-positive tumors (95%) stained positive for pEGFR and had a median pEGFR immunohistochemical score of 5. Disease control rates differed between patients with a pEGFR immunohistochemical score = 7 (7/7, 100%) and less than 7 (7/13, 53.8%), showing a trend toward higher disease control in patients with high levels of pEGFR (= 7) who were treated with cetuximab with or without irinotecan (P= .05).

In addition to well-known chemotherapeutic agents used in the treatment of solid cancers, promising novel cytotoxic agents are being investigated. Among them are analogs of existing cytotoxic agents, aimed at improving the therapeutic index, and new families such as the epothilone compounds. Agents that target the tyrosine kinase-dependent pathways, farnesyl transferase modulators, Raf kinase inhibitors, antisense molecules to Bcl-2 and proteasome modulators, agents that bind to key proteins involved in critical phases of the cell cycle, as well as antiangiogenesis strategies, are all promising approaches in the treatment of solid cancers. The combination of cytotoxics, hormonal agents or radiotherapy with new molecular-targeted therapies represents one of the main strategies to improve survival in solid cancers. A clinical perspective of these agents as monotherapy or combination therapy will be presented in this paper.

Despite a decreased incidence, gastric cancer remains a leading cause of death worldwide. The only potentially curative modality for localised gastric cancer is surgery. However, overall 5-year survival does not exceed 40%. Although extensive surgery seems to increase survival in Japanese patients, this has not yet been demonstrated in Western patients. The pattern of recurrence of gastric cancer would suggest that both local and systemic treatment are required to improve survival. To date, there is no evidence that adjuvant treatment is effective. Some trials investigating preoperative chemotherapy with various combinations of etoposide, fluorouracil, cisplatin and doxorubicin in locally advanced disease suggest that a reduction in the bulk of the localised tumour may increase the curative resection rate. Advanced disease remains poorly controlled. The most effective treatments appear to be a combination of fluorouracil, methotrexate and doxorubicin (FAMTX), and of fluorouracil and cisplatin. Response rates range from 25 to 50%, and median survival from 6 to 13 months. New agents and new therapeutic approaches are required to improve the poor prognosis of gastric cancer patients.

A 54-year-old man with grade 2 rectal neuroendocrine tumor and hepatic, pancreatic, and bone metastases was treated with 177Lu-DOTATATE as second-line therapy, after failure of somatostatin analogues. Two weeks after the first injection, he presented at the emergency department with acute pancreatitis. We hypothesized that this unusual adverse event, never been reported so far, was the result of acute tumor irradiation after PRRT, leading to peritumoral inflammation and edema with obstruction of an accessory pancreatic duct.

Differentiated-type Intraepithelial Neoplasia (DIN) is defined as HPV-negative squamous intraepithelial proliferation with abnormal keratinocyte differentiation and basal cell atypia, originally described in the vulva, with following descriptions in the oral cavity. DIN occurring in the anus is quite rare, and to the best of our knowledge, only one publication reported it. In this report, we describe the clinicopathological features of this entity on anal margin, associated with invasive squamous cell carcinoma. In addition, using the next generation sequencing (NGS) technique, we have demonstrated TP53 mutation in the invasive component but not in the associated DIN-like lesion, where p53 immunohistochemical expression was restricted to basal layers.