Tumor cells use preexisting prosurvival signaling pathways to evade the damaging and cytotoxic effects of anticancer agents. Radiation therapy is a primary form of cytotoxic anticancer treatment, but agents that successfully modify the radiation response in vivo are lacking. MicroRNAs (miRNA) are global gene regulators that play critical roles in oncogenesis and have been found to regulate prosurvival pathways. However, there is little understanding of how cellular miRNA expression affects the response of a cancer to cytotoxic therapy and ultimately outcome. The let-7 family of miRNAs regulates expression of oncogenes, such as RAS, and is specifically down-regulated in many cancer subtypes. In fact, low levels of let-7 predict a poor outcome in lung cancer. Here, we report that the let-7 family of miRNAs is overrepresented in a class of miRNAs exhibiting altered expression in response to radiation. More strikingly, we also can create a radiosensitive state when the select let-7 family of miRNAs is overexpressed in vitro in lung cancer cells and in vivo in a Caenorhabditis elegans model of radiation-induced cell death, whereas decreasing their levels causes radioresistance. In C. elegans, we show that this is partly through control of the protooncogene homologue let-60/RAS and genes in the DNA damage response pathway. These findings are the first direct evidence that miRNAs can suppress resistance to anticancer cytotoxic therapy, a common feature of cancer cells, and suggest that miRNAs may be a viable tool to augment current cancer therapies. [Cancer Res 2007;67(23):11111-6]

MicroRNAs (miRNAs) are important regulators of cell fate determination and homeostasis. Expression of these small RNA genes is tightly regulated during development and in normal tissues, but they are often misregulated in cancer. MiRNA expression is also affected by DNA damaging agents, such as radiation. In particular, mammalian miR-34 is upregulated by p53 in response to radiation, but little is known about the role of this miRNA in vivo. Here we show that Caenorhabditis elegans with loss-of-function mutations in the mir-34 gene have an abnormal cellular survival response to radiation; these animals are highly radiosensitive in the soma and radioresistant in the germline. These findings show a role for mir-34 in both apoptotic and non-apoptotic cell death in vivo, much like that of cep-1, the C. elegans p53 homolog. These results have been additionally validated in vitro in breast cancer cells, wherein exogenous addition of miR-34 alters cell survival post-radiation. These observations confirm that mir-34 is required for a normal cellular response to DNA damage in vivo resulting in altered cellular survival post-irradiation, and point to a potential therapeutic use for anti-miR-34 as a radiosensitizing agent in p53-mutant breast cancer.

Breast radiation therapy accounts for a significant proportion of patient volume in contemporary radiation oncology practice. In the setting of anticipated resource constraints and widespread community infection with SARS-CoV-2 during the COVID-19 pandemic, measures for balancing both infectious and oncologic risk among patients and providers must be carefully considered. Here, we present evidence-based guidelines for omitting or abbreviating breast cancer radiation therapy, where appropriate, in an effort to mitigate risk to patients and optimize resource utilization. Methods and Materials: Multidisciplinary breast cancer experts at a high-volume comprehensive cancer center convened contingency planning meetings over the early days of the COVID-19 pandemic to review the relevant literature and establish recommendations for the application of hypofractionated and abbreviated breast radiation regimens. Results: Substantial evidence exists to support omitting radiation among certain favorable risk subgroups of patients with breast cancer and for abbreviating or accelerating regimens among others. For those who require either whole-breast or postmastectomy radiation, with or without coverage of the regional lymph nodes, a growing body of literature supports various hypofractionated approaches that appear safe and effective. Conclusions: In the setting of a public health emergency with the potential to strain critical healthcare resources and place patients at risk of infection, the parsimonious application of breast radiation therapy may alleviate a significant clinical burden without compromising long-term oncologic outcomes. The judicious and personalized use of immature study data may be warranted in the setting of a competing mortality risk from this widespread pandemic.

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Purpose Telemedicine was rapidly implemented for initial consultations and radiation treatment planning in the wake of the coronavirus disease 2019 (COVID-19) pandemic. In this study, we explore utilization of and physician perspectives on this approach in an attempt to identify patient populations that may benefit most from virtual care. Methods and Materials This is a mixed-methods study with a convergent design. Approximately 6 to 8 weeks after implementation of telemedicine, all radiation oncologists in a single academic radiation oncology department were invited to participate in either semistructured interviews with embedded survey questions or a concurrently administered survey only. Rapid qualitative analysis was used to identify common themes, and quantitative data was assessed using descriptive statistics and univariable analyses. Results At the apex of the pandemic, 92% of radiation oncology visits were conducted via telemedicine. In total, 51 of 61 radiation oncologists participated in the study (response rate 84%). Most (71%) reported no difference in ability to treat cancer appropriately via telemedicine, which was more common among specialized physicians ( P = .01) but not those with higher visit volume or years of experience. Over half (55%) perceived no difference or even improvement in overall visit quality with telemedicine. Virtual visits were deemed acceptable for a median of 70% to 96% of patients, which varied by disease site. Need for physical examination, and availability of an acceptable proxy, factored into telemedicine acceptability. Most (88%) found telemedicine better than expected, but opinions were split on how telemedicine would affect physician burnout. Almost all (96%) foresaw a role for telemedicine beyond the pandemic and would opt for a median of 50% (interquartile range 20%-66%) of visits conducted via telemedicine. Conclusions Among radiation oncologists in an academic setting, telemedicine was perceived to be highly appropriate and acceptable for most patients. Future studies should focus on identifying the 5% to 30% of patients whose care may be optimized with in-person visits, and if there is alignment with patient preferences.