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Background Concurrent chemoradiotherapy (CCRT) is the standard treatment for patients with locally advanced non–small-cell lung cell cancer (LA-NSCLC). We conducted a phase I/II study of biweekly carboplatin and nab-paclitaxel (nab-PTX) with radiotherapy (RT). Materials and Methods In the phase I part, patients with inoperable stage IIIA/IIIB NSCLC were treated with carboplatin (area under the time-concentration curve, 4) and nab-PTX (60-100 mg/m2) on days 1, 15, and 29. Thoracic RT was administered from day 1 to a total dose of 60 Gy in 30 fractions. In the phase II part, patients were administered carboplatin and nab-PTX on days 1, 15, and 29 at the recommended dose (RD). The primary endpoint of the phase I part was to determine the maximum tolerated dose and the RD. In the phase II part, the primary endpoint was 2-year overall survival (OS) rate, and secondary endpoints were the objective response rate, progression-free survival, OS, and safety profile. Results In the phase I part, although maximum tolerated dose was not obtained, the RD was carboplatin (area under the time-concentration curve, 4) and nab-PTX (100 mg/m2). Of the evaluable 28 patients, the rate of 2-year OS was 67.8% (95% confidence interval, 49.3%-82.1%). The objective response rate was 96.4%, and the median follow-up time was 33.2 months. The median progression-free survival was 18.2 months (95% confidence interval, 13.1 months to not reached). The most common toxicities of grade 3 or higher were neutropenia (60.5%), anemia (14.2%), thrombocytopenia (7.2%), and pneumonitis (3.6%). Conclusions This study achieved the primary endpoint. Biweekly carboplatin and nab-PTX with concurrent RT was well-tolerated and exerted promising antitumor activity.

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.

Lung cancer with low average iodine density measured via contrast-enhanced computed tomography (CT) using dual-energy CT technology has shown a reduced local control rate after stereotactic body radiotherapy (SBRT). The current study therefore investigated the relationship between low iodine density tumor area and its ratio and local recurrence after SBRT. Dual-energy CT was performed on the day before SBRT initiation, with a low iodine density tumor area being defined as that with an iodine density of

To evaluate the effect of 6-cycle completion and earlier use of radium-233 dichloride (Ra223) on the prognosis of patients with metastatic castration-resistant prostate cancer (mCRPC).We retrospectively evaluated 75 patients with bone metastases-predominant mCRPC who were treated with Ra223 between August 2016 and August 2021. The primary purpose of the study was to assess the effect of Ra223 completion (6 cycles) on patient prognosis, and the secondary purpose was to investigate factors associated with Ra223 incompletion (fewer than 6 cycles) and overall survival.The median age of the patients was 72 years. The median number of Ra223 administrations was 6 (interquartile range, 5-6), and the median Ra223 completion rate was 75%. The median time from mCRPC diagnosis to Ra223 administration was 17 months, and the median number of prior treatments was 2. Multivariable analysis indicated that unfavorable performance status (0), prostate-specific antigen (PSA) level10 ng/ml, extension of bone metastasis score 3 to 4, and Ra223 incompletion were significantly associated with poor overall survival. In addition, EOD 3 to 4 and 3 or more prior CRPC treatments were significantly associated with Ra223 incompletion.Six-cycle completion and earlier administration of Ra233 are potentially associated with favorable survival. Unfavorable factors (EOD 3-4 and ≥3 prior treatments) were significantly associated with Ra223 incompletion.

A 42-year-old man visited a community hospital with chief complaints of lumbago and dyschesia. Computed tomography (CT) showed multiple lung, lymph node, and bone metastases and the irregular enlarged prostate with urinary bladder invasion. Serum prostate-specific antigen (PSA) was 544.0 ng/mL. Histological evaluation showed adenocarcinoma with the Gleason score 5+4, and the clinical stage was T4N1M1c as an initial diagnosis. Although androgen deprivation therapy was performed immediately, he had castration-resistant PCa after 3 months. Therefore, he received 6 courses of docetaxel chemotherapy every 3 weeks. Serum PSA was decreased to 0.2 ng/mL, and multiple metastases and prostate size were obviously reduced based on CT. He underwent robot-assisted radical prostatectomy and radiation therapy for prostatic fossa and multiple metastases. Although serum PSA level remained low, CT showed multiple liver metastases after 3 years from surgery. He received the combination therapy of cisplatin and etoposide (PE) every 4 weeks. Liver metastases had complete response. However, he visited our hospital with complaint of vomiting and a right drooping eyelid after 6 weeks from withdrawal of PE therapy. T2-weighted magnetic resonance imaging revealed multiple leptomeningeal metastases (LM). He received RT for the brain and was administered amrubicin. However, he died of PCa after 6 weeks from the diagnosis of LM.

We evaluated the efficacy and toxicity of accelerated hypofractionated radiotherapy (ahypof-rt) for central-type small lung tumours. Between November 2006 and January 2015, 40 patients with central-type small lung tumours underwent ahypof-rt delivered using 10 MV X-rays and a coplanar 3-field technique. The number of fractions ranged from 24 to 28, with a fraction size of 2.5&ndash, 3 Gy. A total dose of 69&ndash, 75 Gy to the isocentre of the planning target volume was administered to each patient. Cumulative survival and local control rates were calculated using the Kaplan&ndash, Meier method. The 27 men and 13 women enrolled in the study had a median age of 79 years (range: 60&minus, 87 years). The tumour stage was T1a in 9 patients, T1b in 17 patients, and T2a in 14 patients, with a median size of 26.5 cm (range: 11&ndash, 49 cm). The median follow-up period was 23 months. A complete response was achieved in 3 patients (7.5%), and a partial response, in 17 patients (42.5%). The overall 2-year and 3-year local control rates were 87.3% and 81.8% respectively, the 2-year and 3-year overall survival rates were 78.9% and 66.7% respectively. Grade 3 pneumonitis occurred in 3 patients, no other severe adverse events (&ge, grade 3) were observed in any patient. Accelerated hypofractionated radiotherapy using a fraction size of 2.5&ndash, 3 Gy was highly safe and can be a more effective treatment option than conventional radiotherapy for patients with central-type small lung tumours.

The aim was to determine the dose-specific incidence and predictors of seed loss/migration after permanent seed implantation (PI) for localized prostate cancer. The records of 79 patients with T1c–T3a prostate cancer who underwent prostate brachytherapy with loose iodine-125 seeds were retrospectively reviewed. Of these patients, 33 with low or intermediate risk underwent PI with the prescribed dose of 160 Gy for the clinical target volume (CTV), and 46 with high risk underwent PI with 110 Gy for the CTV followed by external beam radiotherapy (EBRT) with 45 Gy. Each CTV was defined as a contoured prostate. After PI, the incidence of seed loss/migration was assessed by a series of radiographs. Seed migration occurred in 22 (0.479 %) of 4589 implanted seeds 1 month after implantation. In PI alone, the number of needles (P = 0.081) and the number of seeds (P = 0.071) showed a trend for a difference between those with and without seed loss. In PI + EBRT, there was a significant difference in the discrepancy between the seed numbers calculated by the nomogram and actually implanted (P = 0.032). It is suggested that the discrepancy in seed numbers might be the predictor for seed migration in PI with 110 Gy.

Background The efficacy, toxicity, and prognostic factors of high-dose proton beam therapy (PBT) for peripheral stage I non-small-cell lung cancer were assessed in this retrospective study. Materials and Methods Fifty patients with peripheral stage I non-small-cell lung cancer, two of whom had heterochronic multiple lung cancers, underwent high-dose PBT between January 2009 and September 2014. The relative biological effectiveness of the proton beam was defined as 1.1. The beam energy and spread-out Bragg peak were fine-tuned for the 90% isodose volume of the prescribed dosage to encompass the planning target volume. The cumulative survival curves were calculated using the Kaplan-Meier method. Treatment toxicities were evaluated using version 4 of the Common Terminology Criteria for Adverse Events, version 4. Results The study included 35 males and 15 females with a median age of 72.5 years. The median follow-up period was 22.8 months. The clinical stage was IA in 44 (85%) and IB in eight (15%) tumors. The total dose of PBT was 66 GyE in 10 fractions in all tumors. Three-year overall survival rate among all patients was 87.9% (95% confidence interval [CI], 94.8%-73.2%). Forty-five patients were alive, and 5 were dead. Three-year local control and progression-free survival rates were 95.7% (95% CI, 98.9%-83.8%) and 76.3% (95% CI, 86.9%-59.3%), respectively. Only one patient experienced Grade 2 pneumonitis. Conclusion High-dose PBT may be an effective and safe treatment option for patients with stage I non-small-cell lung cancer.

The aim of this study was to evaluate the efficacy and safety of proton beam therapy for patients with locally recurrent parotid cancer. Between 2009 and 2012, ten patients with locally recurrent parotid gland cancer were treated with proton beam therapy (70.2 Gy equivalents in 32 fractions) with or without intra-arterial infusion chemotherapy of cisplatin (50 mg/body/week, for a total of 5–8 weeks). The median follow-up was 24 months (range 10–49 months). The 1-year overall survival and local control rates were 80 %, and the 3-year overall survival and local control rates were 60 %. None of the patients experienced grade 3–5 toxicities in the treatment or the follow-up periods. These findings suggest that proton beam therapy could be applied effectively and safely for patients with locally recurrent parotid gland cancer.

The purpose of this study was to investigate the prognostic significance of average iodine density as assessed by dual-energy computed tomography (DE-CT) for lung tumors treated with stereotactic body radiotherapy (SBRT). From March 2011 to August 2014, 93 medically inoperable patients with 74 primary lung cancers and 19 lung metastases underwent DE-CT prior to SBRT of a total dose of 45–60 Gy in 5–10 fractions. Of these 93 patients, nine patients had two lung tumors. Thus, 102 lung tumors were included in this study. DE-CT was performed for pretreatment evaluation. Regions of interest were set for the entire tumor, and average iodine density was obtained using a dedicated imaging software and evaluated with regard to local control. The median follow-up period was 23.4 months (range, 1.5–54.5 months). The median value of the average iodine density was 1.86 mg/cm 3 (range, 0.40–9.27 mg/cm 3 ). Two-year local control rates for the high and low average iodine density groups divided by the median value of the average iodine density were 96.9% and 75.7% ( P = 0.006), respectively. Tumors with lower average iodine density showed a worse prognosis, possibly reflecting a hypoxic cell population in the tumor. The average iodine density exhibited a significant impact on local control. Our preliminary results indicate that iodine density evaluated using dual-energy spectral CT may be a useful, noninvasive and quantitative assessment of radio-resistance caused by presumably hypoxic cell populations in tumors.

Aim The purpose of this study was to clarify the efficacy and toxicities of re-irradiation using proton beam therapy combined with weekly intra-arterial chemotherapy for recurrent oral cancer. Methods Between October 2009 and July 2014, 34 patients who had recurrent oral cancer were treated by proton beam therapy combined with intra-arterial infusion chemotherapy at the Southern Tohoku Proton Therapy Center, Japan. Results For all patients, the median follow-up was 25 months (range, 3–77 months). After treatment, 22 patients (65%) achieved a complete response, and 12 patients (35%) achieved a partial response at the primary tumor site. One-year and 2-year overall survival (OS) rates were 62% and 42%, respectively. One-year and 2-year LC rates were 77% and 60%, respectively. No treatment-related deaths were observed during the treatment and follow-up periods. Conclusion Re-irradiation using proton beam therapy combined with weekly intra-arterial chemotherapy improved OS and local control rates compared with other treatment modalities and could become a new treatment modality for patients with recurrent oral cancer.

Background The purpose of this study was to evaluate the efficacy and toxicities of proton beam therapy combined with intra-arterial infusion chemotherapy via superficial temporal and occipital arteries for recurrent oral cavity squamous cell carcinoma (SCC). Methods Between October 2009 and June 2013, 46 patients with recurrent oral cavity SCC were treated by proton beam therapy combined with intra-arterial infusion chemotherapy of cisplatin (CDDP) and docetaxel. Treatment consisted of proton beam therapy (28.6–74.8 GyE in 13–34 fractions) and intra-arterial infusion chemotherapy (CDDP, 30–50 mg/body/week; docetaxel, 5–25 mg/body/week). Results One-year and 2-year overall survival (OS) rates were 65% and 46%, respectively. One-year and 2-year local control rates were 81% and 70%, respectively. Conclusion These findings suggest that proton beam therapy combined with intra-arterial infusion chemotherapy could be applied effectively and safely for patients with recurrent oral cavity SCC. © 2016 Wiley Periodicals, Inc. Head Neck, 2016

Background. In an aging society, increasing number of older patients are diagnosed with esophageal cancer. The purpose of this study was to assess the clinical efficacy and safety of proton beam therapy for older patients with esophageal cancer. Patients and methods. Older patients (age: ≥ 65 years) newly diagnosed with esophageal cancer between January 2009 and June 2013 were enrolled in this study. All patients underwent either proton beam therapy alone or proton beam therapy with initial X-ray irradiation. Toxicities were evaluated using the Common Terminology Criteria for Adverse Events version 4.0. Results. Twenty patients were eligible for this study and all completed the treatment. The median age was 78 years (range: 65–89 years) and the median follow-up time was 26.5 months (range: 6–62 months). Seven patients had lymph node metastases and 10 had stage II/III cancer. The median dose of proton beam therapy was 72.6 Gy relative biological dose effectiveness (RBE) (range: 66–74.8 Gy [RBE]) for proton beam therapy alone and 33 Gy (RBE) (range: 30.8–39.6 Gy [RBE]; total dose range: 66.8–75.6 Gy [RBE]) for proton beam therapy with initial X-ray irradiation. The 2-year overall survival rate was 81.8% (95% confidence interval [CI]: 62.4%–100%), and the 2-year local control rate was 89.4% (95% CI: 75.5%–100%). Grade 2 or 3 toxicities occurred in some cases; however, no grade 4 or 5 toxicity was observed. Conclusions. High-dose (66–75.6 Gy [RBE]) proton beam therapy without chemotherapy was an efficacious and safe treatment for older patients with esophageal cancer.

Background The purpose of this study was to evaluate the impact of markerless on-board kilovoltage (kV) cone-beam computed tomography (CBCT)-based positioning uncertainty on determination of the planning target volume (PTV) margin by comparison with kV on-board imaging (OBI) with gold fiducial markers (FMs), and to validate a methodology for the evaluation of PTV margins for markerless kV-CBCT in prostate image-guided radiotherapy (IGRT). Methods A total of 1177 pre- and 1177 post-treatment kV-OBI and 1177 pre- and 206 post-treatment kV-CBCT images were analyzed in 25 patients who received prostate IGRT with daily localization by implanted FMs. Intrafractional motion of the prostate was evaluated between each pre- and post-treatment image with these two different techniques. The differences in prostate deviations and intrafractional motions between matching by FM in kV-OBI (OBI-FM) and matching by soft tissues in kV-CBCT (CBCT-ST) were compared by Bland-Altman limits of agreement. Compensated PTV margins were determined and compensated by references. Results Mean differences between OBI-FM and CBCT-ST in the anterior to posterior (AP), superior to inferior (SI), and left to right (LR) directions were − 0.43 ± 1.45, − 0.09 ± 1.65, and − 0.12 ± 0.80 mm, respectively, with R2 = 0.85, 0.88, and 0.83, respectively. Intrafractional motions obtained from CBCT-ST were 0.00 ± 1.46, 0.02 ± 1.49, and 0.15 ± 0.64 mm, respectively, which were smaller than the results from OBI-FM, with 0.43 ± 1.90, 0.12 ± 1.98, and 0.26 ± 0.80 mm, respectively, with R2 = 0.42, 0.33, and 0.16, respectively. Bland-Altman analysis showed a significant proportional bias. PTV margins of 1.5 mm, 1.4 mm, and 0.9 mm for CBCT-ST were calculated from the values of CBCT-ST, which were also smaller than the values of 3.15 mm, 3.66 mm, and 1.60 mm from OBI-FM. The practical PTV margin for CBCT-ST was compensated with the values from OBI-FM as 4.1 mm, 4.8 mm, and 2.2 mm. Conclusions PTV margins calculated from CBCT-ST might be underestimated compared to the true PTV margins. To determine a reliable CBCT-ST-based PTV margin, at least the systemic error Σ and the random error σ for on-line matching errors need to be investigated by supportive preliminary FM evaluation at least once.

Background The purpose of this study was to investigate the differences in the dosimetric advantage of using intraoperatively built custom-linked (IBCL) seeds between permanent iodine-125 (I-125) seed implantation (PI) alone and PI followed by external-beam radiation therapy (EBRT) for prostate cancer. Methods We reviewed the records of 62 patients with localized prostate cancer who received transperineal interstitial brachytherapy with I-125 using free seeds or IBCL seeds. Twenty-four low- and intermediate-risk patients underwent PI alone with the prescribed dose of 160 Gy, and 39 high-risk patients underwent PI with 110 Gy, followed by EBRT with 45 Gy (PI + EBRT). Intraoperative and post-implant dosimetric parameters 1 month after implantation were collected and analyzed. Results The numbers of patients implanted with free seeds and IBCL seeds were 14 (58.3%) and 10 (41.7%), respectively, in the PI group and 25 (65.8%) and 13 (34.2%), respectively, in the PI + EBRT group. In the PI group, although there were significant differences in prostate V100 (p = 0.003) and D90 (p = 0.009) and rectum V100 (p = 0.026) on intraoperative dosimetry, these differences were not found on post-implant dosimetry. In the PI + EBRT group, the dosimetric parameters of IBCL seeds, such as prostate V200 (p = 0.013) and V250 (p = 0.010) and urethra D30 (p = 0.038), were better than those of free seeds on intraoperative dosimetry. Furthermore, even on post-implant dosimetry, prostate D90 (p = 0.004), V150 (p = 0.001), and homogeneity index (HI, p = 0.001), as well as V200 (p = 0.001) and V250 (p = 0.020), and urethra D5 (p = 0.008) as well as D30 (p = 0.003) had a better dosimetric quality in IBCL seeds than in free seeds. There was no significant difference in the operation time between free seeds and IBCL seeds in each PI and PI + EBRT group. Conclusions Our results reveal that greater dosimetric benefits could be obtained using IBCL seeds in the case of permanent implantation with a lower prescribed dose, such as PI + EBRT, rather than PI alone.

The purpose of this study was to investigate clinical outcomes following stereotactic body radiotherapy (SBRT) for lung metastases as oligo-recurrence. From May 2003 to June 2014, records for 66 patients with 76 oligo-recurrences in the lungs treated with SBRT were retrospectively reviewed. Oligo-recurrence primary sites and patient numbers were as follows: lungs, 31; colorectal, 13; head and neck, 10; esophagus, 3; uterus, 3; and others, 6. The median SBRT dose was 50 Gy (range, 45–60 Gy) administered in a median of 5 (range, 5–9) fractions. All patients received SBRT, with no acute toxicity. Surviving patients had a median follow-up time of 36.5 months. The 3-year rates of local control, overall survival and disease-free survival were 90.6%, 76.0% and 53.7%, respectively. Longer disease-free interval from initial treatment to SBRT, and non-colorectal cancer were both associated with favorable outcomes. Disease progression after SBRT occurred in 31 patients, most with distant metastases (n = 24) [among whom, 87.5% (n = 21) had new lung metastases]. Among these 21 patients, 12 were judged as having a second oligo-recurrence. Additional SBRT was performed for these 12 patients, and all 12 tumors were controlled without disease progression. Three patients (4.5%) developed Grade 2 radiation pneumonitis. No other late adverse events of Grade ≥2 were identified. Thus, SBRT for oligo-recurrence achieved acceptable tumor control, with additional SBRT also effective for selected patients with a second oligo-recurrence after primary SBRT.

We conducted a preliminary retrospective evaluation of the efficacy and toxicity of proton-beam therapy (pbt) for stage iii non-small-cell lung cancer. Between January 2009 and August 2013, 27 patients (26 men, 1 woman) with stage iii non-small-cell lung cancer underwent pbt. The relative biologic effectiveness value of the proton beam was defined as 1.1. The beam energy and spread-out Bragg peak were fine-tuned such that the 90% isodose volume of the prescribed dose encompassed the planning target volume. Of the 27 patients, 11 underwent neoadjuvant chemotherapy. Cumulative survival curves were calculated using the Kaplan&ndash, Meier method. Treatment toxicities were evaluated using version 4 of the Common Terminology Criteria for Adverse Events. Median age of the patients was 72 years (range: 57&ndash, 91 years), and median follow-up was 15.4 months (range: 7.8&ndash, 36.9 months). Clinical stage was iiia in 14 patients (52%) and iiib in 13 (48%). The median dose of pbt was 77 GyE (range: 66&ndash, 86.4 GyE). The overall survival rate in the cohort was 92.3% at 1 year and 51.1% at 2 years. Locoregional failure occurred in 7 patients, and distant metastasis, in 10. In 2 patients, initial failure was both locoregional and distant. The 1-year and 2-year rates of local control were 68.1% and 36.4% respectively. The 1-year and 2-year rates of progression-free survival were 39.9% and 21.4% respectively. Two patients experienced grade 3 pneumonitis. For patients with stage iii non-small-cell lung cancer, pbt can be an effective and safe treatment option.

The purpose of this study was to investigate the relationship between tumor size and blood volume for patients with lung tumors, using dual-energy computed tomography (DECT) and a gemstone spectral imaging (GSI) viewer. During the period from March 2011 to March 2013, 50 patients with 57 medically inoperable lung tumors underwent DECT before stereotactic body radiotherapy (SBRT) of 50-60 Gy in 5-6 fractions. DECT was taken for pretreatment evaluation. The region-of-interest for a given spatial placement of the tumors was set, and averages for CT value, water density and iodine density were compared with tumor size. The average values for iodine density in tumors of ≤ 2 cm, 2-3 cm, and >3 cm maximum diameter were 24.7, 19.6 and 16.0 (100 µg/cm(3)), respectively. The average value of the iodine density was significantly lower in larger tumors. No significant correlation was detected between tumor size and average CT value or between tumor size and average water density. Both the average water density and the average CT value were affected by the amount of air in the tumor, but the average iodine density was not affected by air in the tumor. The average water density and the average CT value were significantly correlated, but the average iodine density and the average CT value showed no significant correlation. The blood volume of tumors can be indicated by the average iodine density more accurately than it can by the average CT value. The average iodine density as assessed by DECT might be a non-invasive and quantitative assessment of the radio-resistance ascribable to the hypoxic cell population in a tumor.

The nasal type of extranodal natural killer (NK)/T-cell lymphoma (NKTCL) is a rare aggressive lymphoma with poor prognosis. The reported 5-year overall survival for patients with localized nasal NKTCL treated with cyclophosphamide, hydroxydaunorubicin, oncovin and prednisone (CHOP) is

Differentiation-induction therapy is an attractive approach in leukemia treatment. It has been suggested that the accumulation of intracellular reactive oxygen species (ROS) is involved in megakaryocytic differentiation induced by phorbol 12-myristate 13-acetate (PMA) in the K562 leukemia cell line. Therefore, a ROS-inducible technique could be a powerful method of differentiation induction. Accordingly, we hypothesized that ionizing radiation contributes to the acceleration of megakaryocytic differentiation through the accumulation of intracellular ROS in leukemia cells. In the present study, ionizing radiation was shown to promote PMA-induced megakaryocytic differentiation. Cells with high CD41 expression sustained intracellular ROS levels effectively. The enhancement of differentiation by ionizing radiation was found to be regulated through the mitogen-activated protein kinase (MAPK) pathway, involving both extracellular signal-regulated protein kinase 1/2 (ERK1/2) and p38 MAPK. Ionizing radiation also controlled mRNA expression of the oxidative stress response gene heme oxygenase-1 (HO1). Consequently, we concluded that intracellular ROS, increased by ionizing radiation, modulate megakaryocytic differentiation downstream of the MAPK pathway.

This study aimed to investigate the correlation between the average iodine density (AID) detected by dual-energy computed tomography (DE-CT) and the maximum standardized uptake value (SUVmax) yielded by [18F] fluorodeoxyglucose positron emission tomography (18F-FDG PET) for non–small cell lung cancer (NSCLC) treated with stereotactic body radiotherapy (SBRT). Seventy-four patients with medically inoperable NSCLC who underwent both DE-CT and 18F-FDG PET/CT before SBRT (50‒60 Gy in 5‒6 fractions) were followed up after a median interval of 24.5 months. Kaplan–Meier analysis was used to determine associations between local control (LC) and variables, including AID, SUVmax, tumor size, histology, and prescribed dose. The median AID and SUVmax were 18.64 (range, 1.18–45.31) (100 µg/cm3) and 3.2 (range, 0.7–17.6), respectively. No correlation was observed between AID and SUVmax. Two-year LC rates were 96.2% vs 75.0% (P = 0.039) and 72.0% vs 96.2% (P = 0.002) for patients classified according to high vs low AID or SUVmax, respectively. Two-year LC rates for patients with adenocarcinoma vs squamous cell carcinoma vs unknown cancer were 96.4% vs 67.1% vs 92.9% (P = 0.008), respectively. Multivariate analysis identified SUVmax as a significant predictor of LC. The 2-year LC rate was only 48.5% in the subgroup of lower AID and higher SUVmax vs >90% (range, 94.4–100%) in other subgroups (P = 0.000). Despite the short follow-up period, a reduction in AID and subsequent increase in SUVmax correlated significantly with local failure in SBRT-treated NSCLC patients. Further studies involving larger populations and longer follow-up periods are needed to confirm these results.

頭頸部癌の動注併用放射線療法における動注血管選択度の違いによる治療効果と，動注手技由来合併症を検討した。対象は動注化学療法を施行した頭頸部癌93症例，全247回の動注手技。病期はIV期が過半数。動注手技により超選択的動注群67例と非選択的動注群（金属コイルでの血流改変を併用）26例に分類。このうち根治照射を併用した粘膜扁平上皮癌初回治療例（56例）で一次治療効果を検討したところ，原発巣の治療効果は超選択的動注群42例中CR 27例（64.3%），PR 15例（35.7%），非選択的動注群14例中CR 10例（71.4%），PR 4例（28.6%）で，両群間に有意差はなかった。動注手技由来合併症は全93例で検討したが，超選択的動注群で67例中4例（6.0%），非選択的動注群で26例中1例（3.8%）に生じており両群間に有意差はなかった。放射線療法併用のもと，非選択的動注療法は超選択的動注法と同等に有効な動注法である。

Lymph nodes (LN) and lymphatic drainage were identified by lymphoscintigraphy using ⁹⁹(m)Tc-phytate in order to map the sentinel lymph nodes (SLNs) in patients with malignant skin neoplasms of the lower extremities, and to compare the results with an atlas of Japanese lymphatic anatomy.Sentinel lymphoscintigraphs of 18 patients with malignant skin neoplasms of the lower extremities (9 men, 9 women; age range 45-84 years, mean age 66 years) were analyzed retrospectively, and the LNs detected were identified as SLNs or secondary nodes.The patterns of lymphatic drainage were divided into three different categories: (1) initial drainage into inguinal LN without visualization of popliteal LNs (inguinal type), (2) initial drainage into popliteal LNs and then into intrapelvic LNs (popliteal type), and (3) initial drainage into both popliteal and inguinal LNs (inguinal and popliteal type). More than half of the cases were the inguinal and popliteal type, as both inguinal and popliteal LNs were identified as SLNs. In the cases in which the hallux and its surrounding area were injected, all were the inguinal type and popliteal LNs were not visualized. In one case, only dynamic images detected lymphatic drainage without visualization of popliteal LNs. In contrast to the previously published literature on Japanese lymphatic anatomy, SLN lymphatic drainage from the skin of the lower extremities was wide and overlapping in many areas. However, in agreement with currently accepted anatomy, only the great saphenous lymphatic vessel drained the skin of the hallux and its surrounding area. The present results suggest that it is important to confirm lymphatic drainage in order to identify SLNs in the lower extremities.The patterns of lymphatic drainage from the skin of the foot were divided into three different categories. In contrast to previously published Japanese lymphatic anatomy, lymphatic drainage from the skin of the lower extremities was wide and overlapping in many areas. However, only the great saphenous lymphatic vessel drained the skin of the hallux and its surrounding area in agreement with currently accepted Japanese lymphatic anatomy. It is important to confirm lymphatic drainage to identify SLNs in the lower extremities.

The aim of this study was to investigate the clinical outcome of stereotactic body radiotherapy (SBRT) of 54 Gy in nine fractions for patients with localized lung tumor using a custom-made immobilization system. The subjects were 19 patients who had localized lung tumor (11 primaries, 8 metastases) between May 2003 and October 2005. Treatment was conducted on 19 lung tumors by fixed multiple noncoplanar conformal beams with a standard linear accelerator. The isocentric dose was 54 Gy in nine fractions. The median overall treatment time was 15 days (range 11–22 days). All patients were immobilized by a thermo-shell and a custom-made headrest during the treatment. The crude local tumor control rate was 95% during the follow-up of 9.4–39.5 (median 17.7) months. In-field recurrence was noted in only one patient at the last follow-up. The Kaplan-Meier overall survival rate at 2 years was 89.5%. Grade 1 radiation pneumonia and grade 1 radiation fibrosis were observed in 12 of the 19 patients. Treatment-related severe early and late complications were not observed in this series. The stereotactic body radiotherapy of 54 Gy in nine fractions achieved acceptable tumor control without any severe complications. The results suggest that SBRT can be one of the alternatives for patients with localized lung tumors.

The purpose of this study was to evaluate the efficacy and toxicities of proton beam therapy combined with intra-arterial infusion chemotherapy via superficial temporal and occipital arteries for recurrent oral cavity squamous cell carcinoma (SCC).Between October 2009 and June 2013, 46 patients with recurrent oral cavity SCC were treated by proton beam therapy combined with intra-arterial infusion chemotherapy of cisplatin (CDDP) and docetaxel. Treatment consisted of proton beam therapy (28.6-74.8 GyE in 13-34 fractions) and intra-arterial infusion chemotherapy (CDDP, 30-50 mg/body/week; docetaxel, 5-25 mg/body/week).One-year and 2-year overall survival (OS) rates were 65% and 46%, respectively. One-year and 2-year local control rates were 81% and 70%, respectively.These findings suggest that proton beam therapy combined with intra-arterial infusion chemotherapy could be applied effectively and safely for patients with recurrent oral cavity SCC. © 2016 Wiley Periodicals, Inc. Head Neck 38:1145-1151, 2016.

OBJECTIVE This study aimed to evaluate the efficacy and toxicity of proton beam therapy combined with cisplatin intra-arterial infusion via a superficial temporal artery as treatment for maxillary sinus carcinoma. METHODS Twenty-six patients with confirmed maxillary sinus carcinoma were enrolled in this study from May 2009 to April 2011. Patients underwent proton beam therapy and intra-arterial infusion chemotherapy with cisplatin. RESULTS The median total dose was 70.4 GyE per 32 fractions, and the median dose of cisplatin was 300 mg/body for six cycles of intra-arterial infusion. The 3-year overall survival rate was 58% for all patients (n = 26), 58% for patients with stage T4 disease (n = 12), 57% for patients with

Background Radiation-induced rib fracture after stereotactic body radiotherapy (SBRT) for lung cancer has been recently reported. However, incidence of radiation-induced rib fracture after SBRT using moderate fraction sizes with a long-term follow-up time are not clarified. We examined incidence and risk factors of radiation-induced rib fracture after SBRT using moderate fraction sizes for the patients with peripherally located lung tumor. Methods During 2003–2008, 41 patients with 42 lung tumors were treated with SBRT to 54–56 Gy in 9–7 fractions. The endpoint in the study was radiation-induced rib fracture detected by CT scan after the treatment. All ribs where the irradiated doses were more than 80% of prescribed dose were selected and contoured to build the dose-volume histograms (DVHs). Comparisons of the several factors obtained from the DVHs and the probabilities of rib fracture calculated by Kaplan-Meier method were performed in the study. Results Median follow-up time was 68 months. Among 75 contoured ribs, 23 rib fractures were observed in 34% of the patients during 16–48 months after SBRT, however, no patients complained of chest wall pain. The 4-year probabilities of rib fracture for maximum dose of ribs (Dmax) more than and less than 54 Gy were 47.7% and 12.9% (p = 0.0184), and for fraction size of 6, 7 and 8 Gy were 19.5%, 31.2% and 55.7% (p = 0.0458), respectively. Other factors, such as D2cc, mean dose of ribs, V10–55, age, sex, and planning target volume were not significantly different. Conclusions The doses and fractionations used in this study resulted in no clinically significant rib fractures for this population, but that higher Dmax and dose per fraction treatments resulted in an increase in asymptomatic grade 1 rib fractures.

This multicenter prospective study ( Japanese Radiation Oncology Study Group: JROSG 05-5) aimed to evaluate the effectiveness of postoperative radiotherapy (PORT) in patients with ductal carcinoma in situ (DCIS) with an involved surgical margin or close margin widths of ≤1 mm or less. PORT consisted of whole-breast irradiation (50 Gy in 25 fractions) followed by boost irradiation (10 Gy in 5 fractions). Eligibility criteria were as follows: (i) DCIS without an invasive carcinoma component, (ii) age between 20 and 80 years old, (iii) involved margin or close margin widths of ≤1 mm, (iv) refusal of re-resection, (v) performance status of 0–2, and (vi) written informed consent. The primary endpoint was ipsilateral breast tumor recurrence (IBTR), and secondary endpoints were overall survival (OS), relapse-free survival (RFS), recurrence patterns, and adverse events. A total of 37 patients from 12 institutions were enrolled from January 2007 to May 2009. The median follow-up time was 62 months (range, 28–85 months). The median pathological tumor size was 2.5 cm (range, 0.3–8.5 cm). Of the 37 patients, 21 had involved margins, and 16 had close margins. The 5-year IBTR, OS and RFS rates were 6% (95% confidence interval [CI]: 2–21), 97% (95% CI: 83–99) and 91% (95% CI: 77–97), respectively. Two patients developed local recurrence at the original site after 39 and 58 months. No severe adverse events were found. Our study suggests that this PORT regimen could be a treatment option for patients with DCIS with involved margin or close margin who don't desire re-resection.

Malignant neoplasms of the salivary gland are uncommon entities in which surgical resection of the primary lesion has been accepted as a standard therapeutic option. The efficacy of radiation and systemic chemotherapy has been limited for patients with recurrent, metastatic, or unresectable disease because of unfavorable response rates and the short duration of the response. We treated one patient with recurrent adenoid cystic carcinoma arising from the sublingual gland and one patient with primary adenocarcinoma arising from the parotid gland with transfemoral intraarterial chemotherapy, based on full-dose cisplatin and docetaxel and concurrent external-beam radiotherapy. The doses of cisplatin and docetaxel in the two patients were 80-100 mg/m2 and 10-15 mg/m2, respectively. Docetaxel was infused first, followed by cisplatin. Both patients obtained complete responses. Although complications such as mucositis, anorexia, neutropenia, and ischemic colitis were observed, they were well tolerated and manageable. The concomitant chemoradiotherapy of cisplatin and docetaxel seemed to be a practicable option for patients with recurrent and unresectable salivary gland carcinomas.

Purpose: To evaluate the efficacy and toxicity of hypofractionated conventional conformation radiotherapy (HCCRT) with noninvasive fixation of the skull on patients with single or several brain metastases. Methods and Materials: The subjects were 44 patients who had three or fewer brain metastases (26 solitary, 18 multiple). Treatment was conducted on 65 metastases by rotational conformal beam or multiple fixed coplanar beams with a standard linear accelerator. The planning target volume consisted of the tumor and a 1-cm safety margin. The median isocentric dose was 24 Gy (range, 18–30 Gy) in 3–5 fractions. Whole-brain irradiation was not applied as an initial treatment. Results: Actuarial local tumor control rates at 6 months and 1 year were 78.4% and 71.9%, respectively. In-field recurrence was noted in 10 of 65 tumors, and repeat HCCRT was applied in 5 tumors. Actuarial overall survival rates at 1 year, 2 years, and the median survival time were 50.8%, 24.1%, and 5.8 months, respectively. The patients with an active primary cancer and poor performance status had a poorer prognosis than those without those factors. Actuarial freedom from second brain metastases rates at 6 months, 1 year, and 2 years were 86.6%, 69.0%, and 40.9%, respectively. Second brain metastases were observed in 9 of 44 patients. Lung adenocarcinomas had a higher risk of second brain metastasis than others. Treatment-related severe early or late complications were not observed in this series. Conclusions: Hypofractionated conventional conformation radiotherapy achieved sufficient tumor control and survival. The results suggest that HCCRT would be one of the alternatives for patients with either solitary or several brain metastases.

Hypoxia‑inducible factor 1 (HIF‑1) activates the transcription of genes that act upon the adaptation of cancer cells to hypoxia. LW6, an HIF‑1 inhibitor, was hypothesized to improve resistance to cancer therapy in hypoxic tumors by inhibiting the accumulation of HIF‑1α. A clear anti‑tumor effect under low oxygen conditions would indicate that LW6 may be an improved treatment strategy for cancer in hypoxia. In the present study, the HIF‑1 inhibition potential of LW6 on the growth and apoptosis of A549 lung cancer cells in association with oxygen availability was evaluated. LW6 was observed to inhibit the expression of HIF‑1α induced by hypoxia in A549 cells at 20 mM, independently of the von Hippel‑Lindau protein. In addition, at this concentration, LW6 induced hypoxia‑selective apoptosis together with a reduction in the mitochondrial membrane potential. The intracellular reactive oxygen species levels increased in LW6‑treated hypoxic A549 cells and LW6 induced a hypoxia‑selective increase of mitochondrial O2•‑. In conclusion, LW6 inhibited the growth of hypoxic A549 cells by affecting the mitochondria. The inhibition of the mitochondrial respiratory chain is suggested as a potentially effective strategy to target apoptosis in cancer cells.

Megakaryocytes are generated by the differentiation of megakaryocytic progenitors; however, little information has been reported regarding how ionizing radiation affects the differentiation pathway and cellular responses. Human leukemia K562 cells have been used as a model to study megakaryocytic differentiation. In the present study, to investigate the effects of radiation on phorbol 12-myristate 13-acetate (PMA)-induced megakaryocytic differentiation of K562 cells, the cellular processes responsible for the expression of CD41 antigen (GPIIb/IIIa), which is reported to be expressed early in megakaryocyte maturation, were analyzed. The expression of CD41 antigens was significantly increased 72 h after treatment with both 4 Gy X-irradiation and PMA. In this fraction, two populations, CD41(low) and CD41(high) cells, were detected by flow cytometry. The CD41(high) cells sustained intracellular ROS at the initial level for up to 72 h, but CD41(low) cells had reduced ROS by 48 h. The maximum suppressive effect on CD41 expression was observed when N-acetyl cysteine, which is known to act as a ROS scavenger, was administered 48 h after PMA stimulation. When K562 cells were pretreated with mitogen-activated protein kinase (MAPK) pathway inhibitors, an ERK1/2 inhibitor and a p38 MAPK inhibitor, followed by X-irradiation and PMA stimulation, the reactivity profiles of both inhibitors showed the involvement of MAPK pathway. There is a possibility that the K562 cell population contains at least two types of radiosensitive megakaryocytic progenitors with respect to ROS production mechanisms, and intracellular ROS levels determine the extent of CD41 expression.

The aim of this study was to clarify the current status of combined modality therapy for locally recurrent rectal cancer.Between 2000 and 2011, 43 patients(26 men and 17 women; mean age, 60 years) developed local pelvic recurrence after curative surgery. The recurrence pattern was almost equally distributed as 53% (23/43) pelvic, and 47% (20/43) pelvic and metastatic disease. Regarding the form of local recurrence, localized type and lateral spread type were present in 25 and 18 patients, respectively. In all, 24 patients underwent surgical resection for recurrent disease, and 87% of these patients underwent potentially curative surgery. The 3- and 5-year overall survival rates for patients who were treated with surgical resection were 42% and 29%, respectively. These results were significantly favorable when compared to the non-surgical group of patients who were treated with chemoradiotherapy or chemotherapy. Localized type recurrence is a statistically significant prognostic factor for improved survival compared to lateral spread type recurrence.Preoperative chemoradiotherapy and surgical resection should be a standard treatment option for patients with localized type recurrence, and chemoradiotherapy is better indicated for patients with lateral spread type recurrence.

Purpose: The purpose of this study was to prospectively assess the reproducibility of positioning errors due to temporarily indwelled catheter in urethra-sparing image-guided (IG) IMRT. Methods: Ten patients received urethra-sparing prostate IG-IMRT with implanted fiducials. After the first CT scan was performed in supine position, 6-Fr catheter was indwelled into urethra, and the second CT images were taken for planning. While the PTV received 80 Gy, 5% dose reduction was applied for the urethral PRV along the catheter. Additional CT scans were also performed at 5th and 30th fraction. Positions of interests (POIs) were set on posterior edge of prostate at beam isocenter level (POI1) and cranial and caudal edge of prostatic urethra on the post-indwelled CT images. POIs were copied into the pre-indwelled, 5th and 30th fraction's CT images after fiducial matching on these CT images. The deviation of each POI between pre- and post-indwelled CT and the reproducibility of prostate displacement due to catheter were evaluated. Results: The deviation of POI1 caused by the indwelled catheter to the directions of RL/AP/SI (mm) was 0.20±0.27/−0.64±2.43/1.02±2.31, respectively, and the absolute distances (mm) were 3.15±1.41. The deviation tends to be larger if closer to the caudal edge of prostate. Compared with the pre-indwelled CT scan, a median displacement of all POIs (mm) were 0.3±0.2/2.2±1.1/2.0±2.6 in the post-indwelled, 0.4±0.4/3.4±2.1/2.3±2.6 in 5th, and 0.5±0.5/1.7±2.2/1.9±3.1 in 30th fraction's CT scan with a similar data distribution. There were 6 patients with 5-mm-over displacement in AP and/or CC directions. Conclusion: Reproducibility of positioning errors due to temporarily indwelling catheter was observed. Especially in case of patients with unusually large shifts by indwelling catheter at the planning process, treatment planning should be performed by using the pre-indwelled CT images with transferred contour of the urethra identified by post-indwelled CT images.

In Japan, surgical therapy is utilized as the main treatment modality for anal squamous cell carcinoma (SCC). Subjects were 6 patients with anal SCC treated at our hospital from 2000-2010, and a study was made on the treatment. In the early 3 cases (Stage IIIA, IIIB, IIIB), chemoradiotherapy (CRT) was used as adjuvant therapy on the premise of surgery. All of them were considered as stable disease, and they all experienced postoperative complications. The average length of the hospital stay was 45 days. Two cases are still surviving without recurrence, but the other one developed a distant metastasis. In contrast, we selected CRT with curative intent in the late 3 cases(Stage II, IIIA, IIIB). Two cases were considered as complete response (CR), and the other one considered as partial response (PR) was performed a salvage operation. Two cases are still surviving without recurrence, but the other case metastasized to the internal iliac lymph nodes. CRT with curative intent for anal SCC demonstrated a good antitumor effect. Salvage operation was safely performed, and showed a good prognosis.

Purpose The aim of this work was to present our single-institution experience with fiducial marker-based hybrid evaluation of prostate positioning combined with orthogonal kV portal image which inform the central position of prostate and CBCT which provides the information on localization of the peripheral structures. Methods Twenty-five patients received prostate IMRT with daily localization by use of implanted fiducials. Orthogonal kV portal imaging and CBCT preceded all 977 treatments. After shifts in the AP, SI, and LR dimensions were made from kV imaging, following another shifts were made when more than 2-mm prostate deviation as total sum of all dimensions were detected by CBCT. Post-treatment kV imaging and CBCT were also obtained in 203 treatments (21%). Shifts between two techniques were analyzed, and compared by Bland-Altman limits of agreement. Intrafraction motion and PTV margin were determined from shifts between pre- and post-treatment in each technique. Results Pre-treatment isocenter shift were made based on CBCT in addition to kV imaging in 315 (32%) treatments. Mean differences between kV imaging and CBCT in the AP/SI/LR were −0.10±0.93/− 0.06±0.91/0.15±0.51 mm. The correlation between these techniques was follows: R2 = 0.90, 0.93, 0.94. Bland-Altman 95% confidence intervals were −1.7 to 1.9/−1.7 to 1.8/−1.2 to 0.8 mm, without significant trends. Intrafraction motion for prostate obtained from pre- and post-CBCT were 0.00±0.15/0.02±1.49/0.15±0.64 mm, which were smaller than the results from kV imaging (0.42±1.90/0.12±1.98/0.26±0.80 mm). PTV margins calculated from the results of CBCT were also smaller than kV imaging (3.95 mm vs 5.15 mm, 4.02 mm vs 5.34 mm, 1.75 mm vs 2.18 mm). Conclusion Hybrid evaluation combined with identification of cranial and caudal edge of prostate by using CBCT compensates the uncertainty of prostate positioning originated from independent utilization of kV portal imaging, which enables to set PTV margins that reflect more realistic intrafraction organ motion.