COVID-19 and radiotherapy: potential new strategies for patients management with hypofractionation and telemedicine.

COVID-19 disease is one of the biggest public health challenges in Italy and global healthcare facilities, including radiotherapy departments, faced an unprecedented emergency. Cancer patients are at higher risk of COVID-19 infection because of their immunosuppressive state caused by both tumor itself and anticancer therapy adopted. In this setting, the radiation therapy clinical decision-making process has been partly reconsidered; thus, to reduce treatment duration and minimize infection risk during a pandemic, hypofractionated regimens have been revised. Moreover, telemedicine shows its helpfulness in the radiotherapy field, and patients get the supportive care they need minimizing their access to hospitals. This review aims to point out the importance of hypofractionated RT and telemedicine in cancer patient management in the COVID-19 era.

VMAT partial-breast irradiation: acute toxicity of hypofractionated schedules of 30 Gy in five daily fractions.

PURPOSE: To report acute toxicities in breast cancer (BC) patients (pts) recruited in a prospective trial and treated with accelerated partial-breast irradiation (APBI) using Volumetric Modulated Arc Therapy (VMAT) delivered with a hypofractionated schedule. METHODS: From March 2014 to June 2019, pts with early-stage BC (Stage I), who underwent breast conservative surgery (BCS), were recruited in a prospective study started at the National Cancer Institute of Milan. Pts received APBI with a hypofractionated schedule of 30 Gy in five daily fractions. Radiotherapy treatment (RT) was delivered using VMAT. Acute toxicity was assessed according to RTOG/EORTC criteria at the end of RT. RESULTS: Between March 2014 and June 2019, 151 pts were enrolled in this study. 79 Pts had right-side and 72 had left-side breast cancer. Median age was 69 (range 43-92). All pts presented with pathological stage IA BC, molecular classification was Luminal A in 128/151 (85%) and Luminal B in 23/151 (15%) cases. Acute toxicity, assessed at the end of RT, consisted of G1 erythema in 37/151 (24. 5%) pts and skin toxicities higher than G1, did not occur. Fibrosis G1 and G2 were reported in 41/151 (27. 1%) pts and in 2/151 pts (1. 3%), respectively. Edema G1 occurred in 8/151 (5. 3%) pts and asthenia G1 occurred in 1/151 (0. 6%) pts. CONCLUSIONS: APBI with VMAT proved to be feasible and can be a valid alternative treatment option after BCS in selected early breast cancer pts according to ASTRO guidelines. A longer follow-up is needed to assess late toxicity.

Reirradiation of salivary gland tumors with carbon ion radiotherapy at CNAO.

AIMS: To report oncologic and functional outcomes in terms of tumor control and toxicity of carbon ion radiotherapy (CIRT) in reirradiation setting for recurrent salivary gland tumors at CNAO. METHODS: From November 2013 to September 2016, 51 consecutive patients with inoperable recurrent salivary gland tumors were retreated with CIRT in the frame of the phase II protocol CNAO S14/2012C for recurrent head and neck tumors. RESULTS: Majority of pts (74.5%) had adenoid cystic carcinoma, mainly rcT4a (51%) and rcT4b (37%). Median dose of prior photon based radiotherapy was 60 Gy. Median dose of CIRT was 60 Gy [RBE] at a mean of 3 Gy [RBE] per fraction. During reirradiation, 19 patients (37.3%) experienced grade G1 toxicity, 19 pts (37.3%) had G2 and 2 pts (3.9%) had G3. Median follow up time was 19 months. Twenty one (41.2%) patients had stable disease and 30 (58.8%) tumor progression at the time of last follow up. Furthermore, 9 (18%) patients had G1 late toxicity, 19 (37%) had G2 and 9 (17. 5%) had G3. Using the Kaplan Meier method, progression free survival (actuarial) at one and two years were 71.7% and 52.2% respectively. Estimated overall survival (actuarial) at one and two years were 90.2% and 64%, respectively. CONCLUSIONS: CIRT is a good option for retreatment of inoperable recurrent salivary gland tumors with acceptable rates of acute and late toxicity. Longer follow up time is needed to assess the effectiveness of CIRT in reirradiation setting of salivary gland tumors.

Exosome-mediated delivery of miR-9 induces cancer-associated fibroblast-like properties in human breast fibroblasts.

It is established that the interaction between microenvironment and cancer cells has a critical role in tumor development, given the dependence of neoplastic cells on stromal support. However, how this communication promotes the activation of normal (NFs) into cancer-associated fibroblasts (CAFs) is still not well understood. Most microRNA (miRNA) studies focused on tumor cell, but there is increasing evidence of their involvement in reprogramming NFs into CAFs. Here we show that miR-9, upregulated in various breast cancer cell lines and identified as pro-metastatic miRNA, affects the properties of human breast fibroblasts, enhancing the switch to CAF phenotype, thus contributing to tumor growth. Expressed at higher levels in primary triple-negative breast CAFs versus NFs isolated from patients, miR-9 improves indeed migration and invasion capabilities when transfected in immortalized NFs; viceversa, these properties are strongly impaired in CAFs upon miR-9 inhibition. We also demonstrate that tumor-secreted miR-9 can be transferred via exosomes to recipient NFs and this uptake results in enhanced cell motility. Moreover, we observed that this miRNA is also secreted by fibroblasts and in turn able to alter tumor cell behavior, by modulating its direct target E-cadherin, and NFs themselves. Consistently with the biological effects observed, gene expression profiles of NFs upon transient transfection with miR-9 show the modulation of genes mainly involved in cell motility and extracellular matrix remodeling pathways. Finally, we were able to confirm the capability of NFs transiently transfected with miR-9 to promote in vivo tumor growth. Taken together, these data provide new insights into the role of miR-9 as an important player in the cross-talk between cancer cells and stroma.