Clinical research in small genomically stratified patient populations

The paradigm of early drug development in cancer is shifting from ‘histology-oriented’ to ‘molecularly oriented’ clinical trials. This change can be attributed to the vast amount of tumour biology knowledge generated by large international research initiatives such as The Cancer Genome Atlas (TCGA) and the use of next generation sequencing (NGS) techniques developed in recent years. However, targeting infrequent molecular alterations entails a series of special challenges. The optimal molecular profiling method, the lack of standardised biological thresholds, inter- and intra-tumor heterogeneity, availability of enough tumour material, correct clinical trials design, attrition rate, logistics or costs are only some of the issues that need to be taken into consideration in clinical research in small genomically stratified patient populations. This article examines the most relevant challenges inherent to clinical research in these populations. Moreover, perspectives from the Academia point of view are reviewed as well as initiatives to be taken in forthcoming years.     

Metastasis-associated protein S100A4 induces a network of inflammatory cytokines that activate stromal cells to acquire pro-tumorigenic properties

Tumor cells have the ability to exploit stromal cells to facilitate metastasis. By using malignant melanoma as a model, we show that the stroma adjacent to metastatic lesions is enriched in the known metastasis-promoting protein S100A4. S100A4 stimulates cancer cells to secrete paracrine factors, such as inflammatory cytokines IL8, CCL2 and SAA, which activate stromal cells (endothelial cells and monocytes) so that they acquire tumor-supportive properties. Our data establishes S100A4 as an inducer of a cytokine network enabling tumor cells to engage angiogenic and inflammatory stromal cells, which might contribute to pro-metastatic activity of S100A4.     

Ultrasound of primary thyroid non-Hodgkin's lymphoma

ObjectiveThe aim of this study was to review the high-frequency ultrasonography findings of primary thyroid non-Hodgkin's lymphoma (PT-NHL).MethodsData of 39 patients treated for PT-NHL and 48 patients as controls were retrospectively reviewed.ResultsThe mean age of patients, Hashimoto's thyroiditis, marked hypoechogenicity of the lesion, asymmetrical enlargement of the thyroid, cervical lymph node enlargement, enhancement of posterior echoes, and linear echogenic septations were all more statistically significantly different in the PT-NHL group than in the control group.ConclusionUltrasonographic characteristics predictive of PT-NHL are marked hypoechogenicity in the lesion and asymmetrical enlargement of the thyroid gland.     

Impact of Postoperative Complications on Long-Term Survival After Resection of Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis

Annals of Surgical Oncology - Controversy exists over the relationship between postoperative complications (POCs) and long-term survival for hepatocellular carcinoma (HCC) after hepatectomy. This...     

Identifying the potential long-term survivors among breast cancer patients with distant metastasis

BackgroundWe aimed to develop a prediction model to identify long-term survivors after developing distant metastasis from breast cancer.Patients and methodsFrom the institution's database, we collected data of 547 patients who developed distant metastasis during their follow-ups. We developed a model that predicts the post-metastasis overall survival (PMOS) based on the clinicopathologic factors of the primary tumors and the characteristics of the distant metastasis. For validation, the survival data of 254 patients from four independent institutions were used.ResultsThe median duration of the PMOS was 31.0 months. The characteristics of the initial primary tumor, such as tumor stage, hormone receptor status, and Ki-67 expression level, and the characteristics of the distant metastasis presentation including the duration of disease-free interval, the site of metastasis, and the presence of metastasis-related symptoms were independent prognostic factors determining the PMOS. The association between tumor stage and the PMOS was only seen in tumors with early relapses. The PMOS score, which was developed based on the above six factors, successfully identified patients with superior survival after metastasis. The median PMOS for patients with a PMOS score of <2 and for patients with a PMOS score of >5 were 71.0 and 12 months, respectively. The clinical significance of the PMOS score was further validated using independent multicenter datasets.ConclusionsWe have developed a novel prediction model that can classify breast cancer patients with distant metastasis according to their survival after metastasis. Our model can be a valuable tool to identify long-term survivors who can be potential candidates for more intensive multidisciplinary approaches. Furthermore, our model can provide a more reliable survival information for both physicians and patients during their informed decision-making process.