Validation of a Cox prognostic model for tooth autotransplantation

Abstract Objectives This study aimed to validate our Cox proportional hazards prognostic model for autotransplantation of teeth with complete root formation using prognostic index (PI) and determine whether the prognosis can be predicted. Patients and Methods The Protocol group, as a training data set for validation, consisted of 259 autotransplanted teeth to create a PI using the Cox model, as described previously. The Pre‐protocol group, as the first validation data set, consisted of 95 autotransplanted teeth treated without a protocol. The Post‐protocol group, as the second validation data set, consisted of 61 autotransplanted teeth obtained after the establishment of the prognostic model. Because four prognostic factors, including history of root canal treatment (yes), number of roots (multirooted), source of donor tooth (maxillary tooth), and duration of edentulism (≥2.5 months), were selected as a Cox prognostic model, 16 patterns of PI were constructed. First, the autotransplantated teeth in the Protocol group were divided into low‐ and high‐risk groups respectively according to the median of PI as the cutoff value. The survival curves of low‐ and high‐risk groups were calculated using the Kaplan–Meier method and tested using the log‐rank test. Then, in the Pre‐ and Post‐protocol groups, all transplanted teeth were divided into low‐and high‐risk teeth by the median of PI and the survival curves of low‐ and high‐ risk teeth were analyzed statistically in a similar manner. Results The survival curves of the low‐ and high‐risk groups diverged significantly in the Protocol and Post‐protocol groups. In the Pre‐protocol group, the curves of the low‐ and high‐risk groups were separated, and the low‐risk survival rate was improved. Conclusions Our Cox prognostic model for autotransplantation of teeth with complete root formation was useful in predicting the prognosis by external validation using PI

Development of a Novel Enzyme-Targeting Radiosensitizer (New KORTUC) Using a Gelatin-Based Hydrogel Instead of a Sodium Hyaluronate

We recently developed Kochi Oxydol-Radiation Therapy for Unresectable Carcinomas (KORTUC) as a strategy to increase intratumoral oxygen concentrations and degrade antioxidant enzymes such as peroxidase and catalase. We then developed KORTUC II, which uses sodium hyaluronate containing hydrogen peroxide as a radiosensitizer. KORTUC II requires twice-weekly administration to sustain its effects, but decreasing the frequency of radiosensitizer injections to once-weekly would reduce the burden on the patients and the physicians. The goal of this study was thus to develop a new formulation of KORTUC (New KORTUC) that only requires once-weekly administration. We performed experimental studies using a mouse tumor model and biodegradable hydrogel. C3H/He mice were allocated to control, KORTUC, or hydrogel groups. At 72 h after injection, each tumor was irradiated with a 6 MeV electron beam to a total dose of 30 Gy. During a 62-day observation period, changes in tumor volume and survival rates were assessed in each group. Tumor growth rate was slowest in the hydrogel groups. These data suggest that hydrogel could represent a useful adjunct as a long-acting radiosensitizer in place of sodium hyaluronate. New KORTUC, which contains hydrogen peroxide and hydrogel, exerted a radiosensitizing effect that persisted beyond 72 h following injection of the agent. Use of this new formulation allows radiosensitizer injections to be performed once-weekly with good effect

Reduced-dose WBRT combined with SRS for 1-4 brain metastases aiming at minimizing neurocognitive function deterioration without compromising brain tumor control

Background and purpose: To minimize cognitive decline without increasing brain tumor recurrence (BTR) by reduced-dose whole-brain radiotherapy (RD-WBRT) (25 Gy, 10 fractions) + stereotactic radiosurgery (SRS) in patients with = 70. The primary endpoint was the non-inferiority of BTR at distant sites in the brain (BTR-distant)-free survival at 6 months compared to that of the standard dose (SD)-WBRT (30 Gy, 10 fractions) + SRS arm in a randomized clinical trial (JROSG99-1) of SRS with/without SD-WBRT. Secondary endpoints included BTR at any brain sites (BTR-all) and neurocognitive function assessed by a six-test standardized battery.Results: Forty patients from seven institutions were enrolled (median age 69 years). The primary tumor site was a lung in 28 patients; 20 patients had a solitary brain metastasis. The median survival time was 19.0 months (95 % CI: 13.8 %-27.5 %). The BTR-distant-free survival at 6 months was 76.9 % (59.5 %-87.7 %), which is compa-rable to that of historical control although predetermined non-inferiority (>71 %) could not be confirmed (p = 0.16). The cumulative incidence of BTR-all at 6 months accounting for the competing risk of death was 23.0 % (11.4-37.1), which was not worse than that of historical control (p = 0.774). The frequency of the cumulative incidence of persistent cognitive decline at 6 months was 48.6 % under the [>2.0 SD in >= 1 test] definition.Conclusions: RD-WBRT may yield comparable intracranial tumor control when combined with SRS, and may reduce the risk of neurocognitive decline compared to that after SD-WBRT