Effect of Acupuncture in Pain Management of Head and Neck Cancer Radiotherapy: Prospective Randomized Unicentric Study

This prospective randomized open-label trial aimed to evaluate the role of acupuncture in the treatment of pain related to curative and adjuvant (chemo)radiotherapy of head and neck cancer. Patients in two arms (30 patients in each arm) underwent standard oncology therapy and standard supportive care with or without acupuncture. The stratification factors were the type of treatment and chemotherapy indication. The toxicity assessed was represented by pain rated on a 10-point pain scale and analgesic use. Average pain (AP) and the worst pain during the day (WP) were significantly lower in the acupuncture arm during radiotherapy (AP median 0.16 vs. 1.36, p < 0.001; WP median 0.90 vs. 1.96, p < 0.001) and three months after radiotherapy (AP median 0.07 vs. 0.50, p < 0.001; WP median 0.30 vs. 0.83, p = 0.002). The analgesic consumption between arms was statistically significantly different. A median of the proportion of days when the patients used analgesics was 8% and 32.5% during radiotherapy (p = 0.047) and 0% and 20.8% during three months after radiotherapy (p = 0.006) for the acupuncture and control arm, respectively. Results point out lower analgesic consumption and milder pain in acupuncture arm. Acupuncture consequently offers another alternative to standard treatment leading to a reduction in the toxicity of oncological treatment

Identification of AGR2 Gene-Specific Expression Patterns Associated with Epithelial-Mesenchymal Transition

The TGF-β signaling pathway is involved in numerous cellular processes, and its deregulation may result in cancer development. One of the key processes in tumor progression and metastasis is epithelial to mesenchymal transition (EMT), in which TGF-β signaling plays important roles. Recently, AGR2 was identified as a crucial component of the cellular machinery responsible for maintaining the epithelial phenotype, thereby interfering with the induction of mesenchymal phenotype cells by TGF-β effects in cancer. Here, we performed transcriptomic profiling of A549 lung cancer cells with CRISPR-Cas9 mediated AGR2 knockout with and without TGF-β treatment. We identified significant changes in transcripts associated with focal adhesion and eicosanoid production, in particular arachidonic acid metabolism. Changes in transcripts associated with the focal adhesion pathway were validated by RT-qPCR of COL4A1, COL4A2, FLNA, VAV3, VEGFA, and VINC mRNAs. In addition, immunofluorescence showed the formation of stress fibers and vinculin foci in cells without AGR2 and in response to TGF-β treatment, with synergistic effects observed. These findings imply that both AGR2 downregulation and TGF-β have a role in focal adhesion formation and cancer cell migration and invasion. Transcripts associated with arachidonic acid metabolism were downregulated after both AGR2 knockout and TGF-β treatment and were validated by RT-qPCR of GPX2, PTGS2, and PLA2G4A. Since PGE2 is a product of arachidonic acid metabolism, its lowered concentration in media from AGR2-knockout cells was confirmed by ELISA. Together, our results demonstrate that AGR2 downregulation and TGF-β have an essential role in focal adhesion formation; moreover, we have identified AGR2 as an important component of the arachidonic acid metabolic pathway

Incidence of Hippocampal Metastases: Laterality and Implications for Unilateral Hippocampal Avoiding Whole Brain Radiotherapy

Introduction. Hippocampi sparing whole brain radiotherapy (WBRT) is an evolving approach in the treatment of patients with multiple brain metastases, pursuing mitigation of verbal memory decline as a consequence of hippocampal radiation injury. Accumulating data are showing different postradiotherapy changes in the left and right hippocampus with a theoretical proposal of only unilateral (dominant, left) hippocampal sparing during WBRT. Method. The aim of this retrospective study is to describe spatial distribution of brain metastases on MRI in a cohort of 260 patients (2595 metastases) and to evaluate distribution separately in the left and right hippocampus and in respective hippocampal avoiding zones (HAZ, region with subtherapeutic radiation dose), including evaluation of location of metastatic mass centre. Results. The median number of brain metastases was three, with lung cancer being the most common type of primary tumour; 36% had single metastasis. Almost 8% of patients had metastasis within hippocampus (1.1% of all metastases) and 18.1% of patients within HAZ (3.3% of all metastases). No statistically significant difference was observed in the laterality of hippocampal involvement, also when the location of centre of metastases was analyzed. There were more patients presenting the centre of metastasis within left (15) versus right (6) HAZ approaching the borderline of statistical significance. Conclusion. No significant difference in the laterality of BM seeding within hippocampal structures was observed. The hypothesized unilateral sparing WBRT would have theoretical advantage in about 50% reduction in the risk of subsequent recurrence within spared regions