Oligometastases: history and future vision of breast cancer

Oligometastases, oligo-recurrence, sync-oligometastases and metachronous oligometastases were proposed based on the spectrum theory. This review article, first, described the history of cancer theory. Second, we described the history of the concepts of oligometastases, oligo-recurrence and sync-oligometastases. Finally, we prospect future visions of breast cancer of oligometastases

2D Slice-driven Physics-based 3D Motion Estimation Framework for Pancreatic Radiotherapy

Pancreatic diseases are difficult to treat with high doses of radiation, as they often present both periodic and aperiodic deformations. Nevertheless, we expect that these difficulties can be overcome, and treatment results may be improved with the practical use of a device that can capture 2D slices of organs during irradiation. However, since only a few 2D slices can be taken, the 3D motion needs to be estimated from partially observed information. In this study, we propose a physics-based framework for estimating the 3D motion of organs, regardless of periodicity, from motion information obtained by 2D slices in one or more directions and a regression model that estimates the accuracy of the proposed framework to select the optimal slice. Using information obtained by slice-to-slice registration and setting the surrounding organs as boundaries, the framework drives the physical models for estimating 3D motion. The R2 score of the proposed regression model was greater than 0.9, and the RMSE was 0.357 mm. The mean errors were 5.11 $\pm$ 1.09 mm using an axial slice and 2.13 $\pm$ 0.598 mm using concurrent axial, sagittal, and coronal slices. Our results suggest that the proposed framework is comparable to volume-to-volume registration, and is feasible

What motivated medical students and residents to become radiation oncologists in Japan?—Questionnaire report by the radiotherapy promotion committee of JASTRO

This study aimed to clarify the motivations and timing of the decision to become radiation oncologists. Materials and methods: We conducted an online survey for new members of the Japanese Society for Radiation Oncology (JASTRO). Results: The response rate was 43.3%. Data of the 79 respondents who wanted to obtain a board-certification of JASTRO were analysed. We divided the respondents into two groups: Group A, those who entered a single radiation oncology department, and Group B, those who joined a radiology department in which the radiation oncology department and diagnostic radiology department were integrated. The most common period when respondents were most attracted to radiation oncology was “5th year of university” in Group A and “2nd year of junior residency” and “senior residency” in Group B. Furthermore, 79.5% of Group A and 40% of Group B chose periods before graduation from a university with a significant difference. The most common period when respondents made up their minds to become radiation oncologists was “2nd year of junior residency” in both groups. Internal medicine was the most common department to consider if they did not join the radiation oncology or radiology department. Conclusion: To increase the radiation oncologists, it is crucial to enhance clinical training in the fifth year of university for Group A and to continue an active approach to maintain interest in radiation oncology until the end of junior residency. In Group B facilities, it is desirable to provide undergraduates more opportunities to come in contact with radiation oncology

Nicaraven induces programmed cell death by distinct mechanisms according to the expression levels of Bcl-2 and poly (ADP-ribose) glycohydrolase in cancer cells

The PARP-1 expression level and poly (ADP-ribosyl)ation activity in cancer markedly affect the therapeutic outcome. Nicaraven, a free radical scavenger has been found to inhibit PARP, but the effect on cancer cells is still unclear. In this study, we investigated the potential role and molecular mechanism of nicaraven on cancer cells. Using U937 lymphoma cells and HCT-8 colorectal cancer cells, we found that nicaraven moderately reduced the cell viability of both cells in a dose-dependent manner. Interestingly, nicaraven significantly induced apoptosis of U937 cells that are dominantly expressing Bcl-2 but induced PAR-dependent cell death (parthanatos) of HCT-8 cells that are highly expressing poly (ADP-ribose) glycohydrolase (PARG). Based on our data, nicaraven seems to induce programmed cell death through distinct mechanisms, according to the expression levels of Bcl-2 and PARG in cancer cells

Nicaraven mitigates radiation-induced lung injury by downregulating the NF-κB and TGF-β/Smad pathways to suppress the inflammatory response

Radiation-induced lung injury (RILI) is commonly observed in patients receiving radiotherapy, and clinical prevention and treatment remain difficult. We investigated the effect and mechanism of nicaraven for mitigating RILI. C57BL/6 N mice (12-week-old) were treated daily with 6 Gy X-ray thoracic radiation for 5 days in sequences (cumulative dose of 30 Gy), and nicaraven (50 mg/kg) or placebo was injected intraperitoneally in 10 min after each radiation exposure. Mice were sacrificed and lung tissues were collected for experimental assessments at the next day (acute phase) or 100 days (chronic phase) after the last radiation exposure. Of the acute phase, immunohistochemical analysis of lung tissues showed that radiation significantly induced DNA damage of the lung cells, increased the number of Sca-1+ stem cells, and induced the recruitment of CD11c+, F4/80+ and CD206+ inflammatory cells. However, all these changes in the irradiated lungs were effectively mitigated by nicaraven administration. Western blot analysis showed that nicaraven administration effectively attenuated the radiation-induced upregulation of NFκB, TGF-β, and pSmad2 in lungs. Of the chronic phase, nicaraven administration effectively attenuated the radiationinduced enhancement of α-SMA expression and collagen deposition in lungs. In conclusion we find that nicaraven can effectively mitigate RILI by downregulating NF-κB and TGF-β/pSmad2 pathways to suppress the inflammatory response in the irradiated lungs

Optimization on the dose and time of nicaraven administration for mitigating the side effects of radiotherapy in a preclinical tumor-bearing mouse model

Objective: Radiation-induced lung injury (RILI) is one of the serious complications of radiotherapy. We have recently demonstrated that nicaraven can effectively mitigate RILI in healthy mice. Here, we further tried to optimize the dose and time of nicaraven administration for alleviating the side effects of radiotherapy in tumor-bearing mice.Methods and results: A subcutaneous tumor model was established in the back of the chest in C57BL/6N mice by injecting Lewis lung cancer cells. Therapeutic thoracic irradiations were done, and placebo or different doses of nicaraven (20, 50, 100 mg/kg) were administrated intraperitoneally pre-irradiation (at almost 5–10 min before irradiation) or post-irradiation (within 5 min after irradiation). Mice that received radiotherapy and nicaraven were sacrificed on the 30th day, but control mice were sacrificed on the 15th day. Serum and lung tissues were collected for evaluation. Nicaraven significantly decreased the level of CCL8, but did not clearly change the levels of 8-OHdG, TGF-β, IL-1β, and IL-6 in serum. Besides these, nicaraven effectively decreased the levels of TGF-β, IL-1β, and SOD2 in the lungs, especially by post-irradiation administration with the dose of 20 mg/kg. Although there was no significant difference, the expression of SOD1, 53BP1, and caspase 3 was detected lower in the lungs of mice received nicaraven post-irradiation than that of pre-irradiation.Conclusion: According to our data, the administration of nicaraven at a relatively low dose soon after radiotherapy will be recommended for attenuating the side effects of radiotherapy

Impact of pathological tumor stage for salvage radiotherapy after radical prostatectomy in patients with prostate-specific antigen < 1.0 ng/ml

<p>Abstract</p> <p>Background</p> <p>To evaluate prognostic factors in salvage radiotherapy (RT) for patients with pre-RT prostate-specific antigen (PSA) < 1.0 ng/ml.</p> <p>Methods</p> <p>Between January 2000 and December 2009, 102 patients underwent salvage RT for biochemical failure after radical prostatectomy (RP). Re-failure of PSA after salvage RT was defined as a serum PSA value of 0.2 ng/ml or more above the postradiotherapy nadir followed by another higher value, a continued rise in serum PSA despite salvage RT, or initiation of systemic therapy after completion of salvage RT. Biochemical relapse-free survival (bRFS) was estimated using the Kaplan-Meier method. Multivariate analysis was performed using the Cox proportional hazards regression model.</p> <p>Results</p> <p>The median follow-up period was 44 months (range, 11-103 months). Forty-three patients experienced PSA re-failure after salvage RT. The 4-year bRFS was 50.9% (95% confidence interval [95% CI]: 39.4-62.5%). In the log-rank test, pT3-4 (p < 0.001) and preoperative PSA (p = 0.037) were selected as significant factors. In multivariate analysis, only pT3-4 was a prognostic factor (hazard ratio: 3.512 [95% CI: 1.535-8.037], p = 0.001). The 4-year bRFS rates for pT1-2 and pT3-4 were 79.2% (95% CI: 66.0-92.3%) and 31.7% (95% CI: 17.0-46.4%), respectively.</p> <p>Conclusions</p> <p>In patients who have received salvage RT after RP with PSA < 1.0 ng/ml, pT stage and preoperative PSA were prognostic factors of bRFS. In particular, pT3-4 had a high risk for biochemical recurrence after salvage RT.</p

Outcomes after stereotactic body radiotherapy for lung tumors, with emphasis on comparison of primary lung cancer and metastatic lung tumors

BACKGROUND: The goal of this study was to determine the prognostic factors associated with an improved overall outcome after stereotactic body radiotherapy (SBRT) for primary lung cancer and metastatic lung tumors. METHODS: A total of 229 lung tumors in 201 patients were included in the study. SBRT of 45 Gy in 3 fractions, 48 Gy in 4 fractions, 60 Gy in 8 fractions or 60 Gy in 15 fractions was typically used to treat 172 primary lungs cancer in 164 patients and 57 metastatic lung tumors in 37 patients between January 2001 and December 2011. Prognostic factors for local control (LC) and overall survival (OS) were analyzed using a Cox proportional hazards model. RESULTS: The median biologically effective dose was 105.6 Gy based on alpha/beta = 10 (BED10). The median follow-up period was 41.9 months. The 3-year LC and OS rates were 72.5% and 60.9%, and the 5-year LC and OS rates were 67.8% and 38.1%, respectively. Radiation pneumonitis of grades 2, 3 and 5 occurred in 22 petients, 6 patients and 1 patient, respectively. Multivariate analyses revealed that tumor origin (primary lung cancer or metastatic lung tumor, p < 0.001), tumor diameter (p = 0.005), BED10 (p = 0.029) and date of treatment (p = 0.011) were significant independent predictors for LC and that gender (p = 0.012), tumor origin (p = 0.001) and tumor diameter (p < 0.001) were significant independent predictors for OS. CONCLUSIONS: SBRT resulted in good LC and tolerable treatment-related toxicities. Tumor origin and tumor diameter are significant independent predictors for both overall survival and local control