Photon radiation therapy is a major curative treatment for cancer. However, the lack of robust predictive biomarkers for radiosensitivity precludes personalized radiation therapy. Clonogenic assays are the gold standard method for measuring the radiosensitivity of cancer cells. Although a large number of publications describe the use of clonogenic assays to measure cancer cell radiosensitivity, the robustness of results from different studies is unclear. To address this, we conducted a comprehensive detailed literature search of 256 common cancer cell lines and identified the eight cell lines most-frequently examined for photon sensitivity using clonogenic assays. Survival endpoints and experimental parameters from all 620 relevant experiments were compiled and analyzed. We found that the coefficients of variation for SF2 (surviving fraction after 2 Gy irradiation) and for D10 (dose that yields a surviving fraction of 10%) were below 30% for all cell lines, indicating that SF2 and D10 have acceptable inter-assay precision. These data support further analysis of published data on clonogenic assays using SF2 and D10 as survival endpoints, which facilitates robust identification of biological profiles representative of cancer cell sensitivity to photons.

In cancer therapy today, carbon ion radiotherapy is used mainly as monotherapy, whereas cisplatin is used concomitantly with X-ray radiotherapy. The effectiveness of concomitant carbon ions and cisplatin is unclear. To obtain the information on the mechanisms potentially shared between carbon ions or X-rays and cisplatin, we assessed the correlation of sensitivity to the single treatments. In 20 human cancer cell lines, sensitivity to X-rays strongly correlated with sensitivity to cisplatin, indicating the presence of potentially shared target mechanisms. Interestingly, the correlation of sensitivity to carbon ions and cisplatin was much weaker than that of sensitivity to X-rays and cisplatin, indicating the presence of potentially different target mechanisms between carbon ions and cisplatin. Assessment of clonogenic cell death by 4′,6-diamidino-2-phenylindole dihydrochloride staining showed that mitotic catastrophe was more efficiently induced by carbon ions than by the same physical dose of X-rays, while apoptosis and senescence were not. These data indicate that the correlation of sensitivity to carbon ions and cisplatin is weaker than that of sensitivity to X-rays and cisplatin, which are helpful as biological basis to understand the potentially shared mechanism among these treatments. Further investigation is mandatory to elucidate the clinical efficacy of carbon ions and cisplatin combination.

Carbon-ion radiotherapy (CIRT) holds promise to treat inoperable locally-advanced non-small cell lung carcinoma (NSCLC), a disease poorly controlled by standard chemoradiotherapy using X-rays. Since CIRT is an extremely limited medical resource, selection of NSCLC patients likely to benefit from it is important; however, biological predictors of response to CIRT are ill-defined. The present study investigated the association between the mutational status of EGFR and KRAS, driver genes frequently mutated in NSCLC, and the relative biological effectiveness (RBE) of carbon-ion beams over X-rays. The assessment of 15 NSCLC lines of different EGFR/KRAS mutational status and that of isogenic NSCLC lines expressing wild-type or mutant EGFR revealed that EGFR-mutant NSCLC cells, but not KRAS-mutant cells, show low RBE. This was attributable to (i) the high X-ray sensitivity of EGFR-mutant cells, since EGFR mutation is associated with a defect in non-homologous end joining, a major pathway for DNA double-strand break (DSB) repair, and (ii) the strong cell-killing effect of carbon-ion beams due to poor repair of carbon-ion beam-induced DSBs regardless of EGFR mutation status. These data highlight the potential of EGFR mutation status as a predictor of response to CIRT, i.e., CIRT may show a high therapeutic index in EGFR mutation-negative NSCLC.

Summary: The technology used to add information to a real visual field is defined as augmented reality technology. Augmented reality technology that can interactively manipulate displayed information is called mixed reality technology. HoloLens from Microsoft, which is a head-mounted mixed reality device released in 2016, can display a precise three-dimensional model stably on the real visual field as hologram. If it is possible to accurately superimpose the position/direction of the hologram in the surgical field, surgical navigation-like use can be expected. However, in HoloLens, there was no such function. The authors devised a method that can align the surgical field and holograms precisely within a short time using a simple manual operation. The mechanism is to match the three points on the hologram to the corresponding marking points of the body surface. By making it possible to arbitrarily select any of the three points as a pivot/axis of the rotational movement of the hologram, alignment by manual operation becomes very easy. The alignment between the surgical field and the hologram was good and thus contributed to intraoperative objective judgment. By using the method of this study, the clinical usefulness of the mixed reality device HoloLens will be expanded.

Background: Telementoring is the technology for providing surgical instruction from a remote place via a network. To demonstrate the use of telementoring in craniofacial surgery, Skype and a mixed reality device HoloLens were adopted, and 3-layer facial models had been developed. Methods: A resident in hospital A used the model surgery under remote guidance by a mentor surgeon in hospital B 4 times on different dates. The straight-line between hospitals A and B is 250 km. The mentor gave the resident guidance via Skype and HoloLens, communicating by voice, and video of the surgical field, and providing reference data. Results: There was no delay in voice communication and a delay of <0.5 seconds in the video. The resident was able to confirm the main landmarks of the surgical field and to grasp the situation without problems. The mentor could send appropriate instructions by voice, could point out a specific part by telestration function, and could draw lines on the 2-dimentional images pasted on the operator's field of vision. Discussion: With the use of HoloLens, Skype, and the 3-layer models, it was possible to demonstrate telementoring. The risk of personal information leakage due to data interception seems to be very low because its data communication is encrypted with advanced encryption standard. Conclusion: This telementoring system has various advantages and many improvable aspects in the field of craniofacial surgery.