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The outcomes of three methods of intensity-modulated radiation therapy (IMRT) for localized prostate cancer were evaluated. Between 2010 and 2018, 308 D’Amico intermediate- or high-risk patients were treated with 2.2 Gy daily fractions to a total dose of 74.8 Gy in combination with hormonal therapy. Overall, 165 patients were treated with 5-field IMRT using a sliding window technique, 66 were then treated with helical tomotherapy and 77 were treated with volumetric modulated arc therapy (VMAT). The median age of patients was 71 years. The median follow-up period was 75 months. Five-year overall survival (OS) and biochemical or clinical failure-free survival (FFS) rates were 95.5 and 91.6% in the 5-field IMRT group, 95.1 and 90.3% in the tomotherapy group and 93.0 and 88.6% in the VMAT group, respectively, with no significant differences among the three groups. The 5-year cumulative incidence of late grade ≥2 genitourinary and gastrointestinal toxicities were 7.3 and 6.2%, respectively, for all patients. Late grade ≥2 gastrointestinal toxicities were less frequent in patients undergoing VMAT (0%) than in patients undergoing 5-field IMRT (7.3%) and those undergoing tomotherapy (11%) (P = 0.025), and this finding appeared to be correlated with the better rectal DVH parameters in patients undergoing VMAT. Other toxicities did not differ significantly among the three groups, although bladder dose-volume parameters were slightly worse in the tomotherapy group than in the other groups. Despite differences in the IMRT delivery methods, X-ray energies and daily registration methods, all modalities may be used as IMRT for localized prostate cancer.

Purpose With a new tumor‐tracking system (Synchrony®) for tomotherapy (Radixact®), the internal and set‐up margins can be tightened, like cyberknife (CyberKnife®), in the planning of stereotactic body radiotherapy (SBRT) for prostate cancer. Recently, the usefulness of placing a hydrogel spacer between the prostate and rectum has been established in prostate radiotherapy. We evaluated the characteristics of tomotherapy plans with the tumor‐tracking system and compared them with cyberknife SBRT plans for localized prostate cancer using a hydrogel spacer. Methods In 20 patients, two plans were created and compared using tomotherapy and cyberknife. All patients underwent hydrogel spacer injection behind the prostate before simulation CT and MRI for fusion. For all plans, 36.25 Gy in 7.25‐Gy fractions for a minimum coverage dose of 95% of planning target volume (PTV) (D95%) was prescribed. The D99% of PTV and D0.1 ml of the PTV, urethra, bladder, and rectum were intended to be > 90%, 110–130%, 100–110%

Background Heat shock protein 90 (HSP90) is a molecular chaperone that is responsible for the conformational maintenance of several client proteins that play important roles in DNA damage repair, apoptosis following radiation, and resistance to radiation therapy. DS-2248 (tricyclic pyrazolopyrimidine derivative) is a newly-developed, orally available inhibitor of HSP90 with low adverse effects. We investigated the combined effects of radiation and DS-2248 in vitro and in vivo. Methods SCCVII squamous cell carcinoma cells and tumors transplanted in C3H/HeN mice were used. In vitro combined effects of X-ray radiation and DS-2248 were investigated using a colony assay. Phosphorylated histone H2AX (γH2AX) was quantified after 2-Gy irradiation with or without 24-hour pretreatment with DS-2248. The mice bearing SCCVII tumors received oral DS-2248 10 times over 2 weeks and received local irradiation with doses of 1, 2, 3, and 4 Gy delivered 6 times over 2 weeks. Then, tumor volumes were measured. Results Radiation plus pretreatment with 50 nM DS-2248 for 24 hours produced synergistic effects on SCCVII cells. γH2AX foci persisted after radiation for longer periods (6 and 24 hours) in DS-2248-treated cells than in control cells. In vivo, the combined effects appeared to be additive when 5 or 10 mg/kg DS-2248 was combined with total radiation doses of 6–18 Gy, but the effect was considered supra-additive when 15 mg/kg of DS-2248 was combined with a total dose of 24 Gy. Conclusions The combined effects of DS-2248 and radiation were additive at low drug and radiation doses, but may have been supra-additive at higher doses. Inhibition of slow repair of DNA double strand breaks (i.e., homologous recombination) was considered to contribute to this combined effect.

Cancer‐specific death (CSD) and non‐cancer‐specific death (non‐CSD) after stereotactic body radiotherapy (SBRT) for pulmonary oligometastases have not been studied in detail. The aim of this study was to determine the cumulative incidences of CSD and non‐CSD and to reveal prognostic factors. Data from a large survey of SBRT for pulmonary oligometastases were used for analyses, and patients with unknown cause of death were excluded from current analyses. CSD was primary cancer death and non‐CSD was non‐primary cancer death including a series of cancer treatment‐related deaths. Cumulative incidences were calculated using the Kaplan‐Meier method and a stratified Cox regression model was used for multivariate analyses (MVA). Fifty‐two patients with an unknown death were excluded and a total of 1326 patients was selected. CSD and non‐CSD occurred in 375 and 109 patients, respectively. The median OS period was 53.2 months and the cumulative incidences of 1‐, 3‐, and 5‐year CSD vs. non‐CSD rates were 6.5% vs. 2.3%, 29.5% vs. 8.6%, and 41.2% vs. 11.0%, respectively. In MVA, the incidence of CSD was related to performance status (1 vs. 0; p, The incidences cancer‐specific death and non‐cancer‐specific death after stereotactic body radiotherapy for pulmonary oligometastases were 29.5 and 8.6% at 3 years, respectively. Cancer‐specific death significantly related to performance status, oligometastatic state or disease‐free interval and maximum tumor diameter, on the other hand, non‐cancer‐specific death significantly related to age and tumor‐located lung lobe.

This study is a subset analysis of a retrospective multicenter study performed in Japan and its purpose was to investigate the effectiveness of stereotactic body radiotherapy (SBRT) for pulmonary oligometastases from colorectal cancer. Local control (LC), freedom from further metastases, relapse-free survival and overall survival (OS) after SBRT were retrospectively analyzed. The Kaplan–Meier method was used to estimate lifetime data and the log-rank test was performed as univariate analyses. The Cox proportional hazards model was applied in multivariate analyses. Data for 330 patients with 371 tumors were used for analyses. The median follow-up period was 25.0 months. The 3-year LC, freedom from further metastases, relapse-free survival and OS rates were 64.9, 34.9, 24.9 and 63.4%, respectively. The results of multivariate analyses showed that a higher LC rate was associated with no history of local therapy for oligometastases (P = 0.01), SBRT without concurrent chemotherapy (P

The purpose of this multi-institutional Phase II trial study was to prospectively investigate the efficacy of the herbal medicine TJ-14 for acute radiation-induced enteritis (ARE). TJ-14 was administered orally as a first-line treatment for ARE. The primary end point was efficacy at 1 week. The secondary end points were: (i) the efficacy of TJ-14 at 2 and 3 weeks after its administration, (ii) the quality of life score (FACT-G) at 1, 2 and 3 weeks after its administration, and (iii) adverse events. If the efficacy of TJ-14 was observed in eight patients or fewer, its efficacy was rejected. Results: Forty patients receiving pelvic radiotherapy were enrolled. Of these, 22 developed ARE and received TJ-14. Among these, 19 had cervical cancer and 9 received chemoradiotherapy. TJ-14 efficacy was shown in 19 out of the 22 patients (86%). Stool frequency per day at 1 week significantly decreased (mean ± SD: 4.9 ± 2.1 vs 3.7 ± 1.9, P = 0.02). This effect continued at 2 (2.2 ± 1.4, P = 0.004) and 3 weeks (2.1 ± 0.9, P = 0.05). Thirteen out of the 22 patients (59%) continued TJ-14 until the end of radiotherapy. FACT-G score deterioration was not observed after the administration of TJ-14. Grade 1 hypokalemia was observed in 4 patients, and Grade 1 constipation in 3. We concluded that TJ-14 is sufficiently promising to be examined in a Phase III trial. A randomized controlled trial is currently being planned.

Background Despite advances in chemotherapy, curing multiple liver metastases is quite rare. Even when response is obtained, regrowth of the tumors is almost inevitable. We aimed to evaluate the efficacy and adverse events of helical tomotherapy for chemo‐refractory multiple liver metastases. Methods Forty‐five patients with chemo‐refractory multiple (3‐10) liver metastases after standard systemic chemotherapy entered the single‐institutional prospective study. Liver metastases were the major disease; however, 31 also had uncontrolled primary lesions and/or other metastases. The prescribed dose was 55 Gy in 25 fractions. The median planning target volume (PTV) and normal liver volume (NLV) of first treatment were 128 cm3 and 1175 cm3, respectively. The median of V15Gy, V30Gy, and mean dose to NLV were 45%, 23%, and 19.4 Gy, respectively. Results Forty‐two patients (93%) completed the planned treatment. Median survival time (MST) for all patients was 8 months, and the 1‐year survival rate was 29%. The median local control (LC) period was 5 months and the 6‐month control rate of irradiated tumors was 33%. A ≥30% decrease in tumor markers was observed in 31%. The most common grade 3 toxicity was lymphocytopenia (40%), followed by fatigue (6%). Radiation‐induced liver disease (RILD) was not observed. Pancreatic cancer as the primary tumor, distant metastases outside the liver, low pretreatment neutrophil‐to‐lymphocyte ratio (NLR), and low pretreatment monocyte‐to‐lymphocyte ratio (MLR) were associated with poorer prognoses. Conclusions Helical tomotherapy for chemo‐refractory multiple liver metastases is a feasible and potentially effective treatment. Incorporating tomotherapy into the first‐line treatment in combination with systemic chemotherapy should be considered. Trial registration number CROG 12005., Despite the remarkable advances of systemic chemotherapy for multiple liver metastases, the efficacy is still limited and cure of the multiple lesions is difficult. Helical tomotherapy for chemo‐refractory multiple liver metastases was suggested to be a feasible and potentially effective treatment with acceptable adverse events.

We evaluated long-term outcomes of three protocols of intensity-modulated radiation therapy (IMRT) for localized prostate cancer. Between 2005 and 2014, 348 patients were treated with 5-field IMRT. The first 74 patients were treated with a daily fraction of 2.0 Gy to 74 Gy (low-risk prostate cancer) or 78 Gy (intermediate- or high-risk prostate cancer); then 101 patients were treated with 2.1-Gy daily fractions to 73.5 or 77.7 Gy. More recently, 173 patients were treated with 2.2-Gy fractions to 72.6 or 74.8 Gy. The median age of all patients was 70 years and the median follow-up period was 82 months. The median follow-up periods were 124 months in the 2.0-Gy group, 98 months in the 2.1-Gy group, and 69 months in the 2.2-Gy group. The overall and prostate-specific antigen (PSA) failure-free survival (PSA-FFS) rates were, respectively, 89 and 68% at 10 years for the 2.0-Gy group, 91 and 84% at 8 years for the 2.1-Gy group, and 93 and 92% at 6 years for the 2.2-Gy group. The PSA-FFS rate for high-risk patients in all groups was 80% at 7 years. The cumulative incidences of Grade ≥2 late genitourinary (GU) and gastrointestinal (GI) toxicity were, respectively, 7.2 and 12.4% at 10 years for the 2.0-Gy group, 7.4 and 14.1% at 8 years for the 2.1-Gy group, and 7.1 and 7.9% at 6 years for the 2.2-Gy group. All three fractionation schedules yielded good tumor control with acceptable toxicities.

Purpose/Objective(s) The cyclooxygenase-2 product prostaglandin E2 (PGE2) promotes tumor growth and metastasis by acting on a family of four G protein-coupled receptors (EP1–4). Recently, an antagonist of PGE2-EP4 (AAT-008) has been newly developed for clinical use. The purpose of this study is to investigate the biological effects of AAT-008 as a radiosensitizer for the treatment of murine colon cancer (CT26WT) in vivo and explore the mechanism using flow cytometry. Materials/Methods CT26WT tumor cells transplanted into the hind legs of BALB/c mice were used. Treatments were carried out when the mean diameter of the tumors reached approximately 10 mm for tumor growth delay assay and 5 mm for flow cytometry (day 0). AAT-008 (0, 3, 10, and 30 mg/kg/day) was administered orally twice a day from day 0 to day 18. The tumor was irradiated at 9 Gy on day 3 for the radiation treatment (RT) group. In the tumor growth assay, twelve mice were used for each group. The three dimensions of each tumor were measured every other day using a caliper and the tumor doubling time was calculated. For the first flow cytometry, the dose of AAT-008 was fixed to 10 mg/kg/day. Administration of AAT-008 and RT dose were the same as in the tumor growth assay. The population of cytotoxic T-cells (CD45+CD8+CD69+: CTL) was investigated using the tumor cells on day 19. For the second flow cytometry, the dose of AAT was fixed to 30 mg/kg/day. AAT-008 was administered from day 0 to day 12. The population of CTL and the ratio of CTL / regulatory T-cells (Foxp3+: Treg) were investigated using the tumor cells on day 13. Results In the tumor growth delay assay, the median tumor doubling times in the 0-, 3-, 10-, and 30-mg group without RT were 3.2, 4.4, 4.4, and 5.7 days, respectively. The times in those dose groups with RT were 6.1, 6.6, 17.3, and 19.8 days, respectively (P Conclusion AAT-008 had a potential of enhancing radiosensitivity in the treatment of colon cancer cells. It was assumed that the optimal dose of AAT-008 with RT was 10 mg/kg/day. It was suggested that AAT-008 stimulated the immune system against the cancer cells.

Background Successful local therapy for oligometastases may lead to longer survival. The purpose of this multicentre retrospective study was to investigate factors affecting the local control (LC) of pulmonary oligometastases treated by stereotactic body radiotherapy (SBRT) and to investigate the impact of LC on survival. Methods The inclusion criteria included 1 to 5 metastases, the primary lesion and other extrathoracic metastases were controlled before SBRT, and the biological effective dose (BED10) of the SBRT was 75 Gy or more. The Cox proportional hazards model was used for analyses. Results Data of 1378 patients with 1547 tumours from 68 institutions were analysed. The median follow-up period was 24.2 months. The one-year, 3-year and 5-year LC rates were 92.1, 81.3 and 78.6%, respectively, and the 1-year, 3-year and 5-year overall survival rates were 90.1, 60.3 and 45.5%, respectively. Multivariate analysis for LC showed that increased maximum tumour diameter (p = 0.011), type A dose calculation algorithm (p = 0.005), shorter overall treatment time of SBRT (p = 0.035) and colorectal primary origin (p p p = 0.013; 2–3 vs. 0, p p = 0.038), squamous cell carcinoma (vs. adenocarcinoma, p = 0.006) and increased maximum tumour diameter (p Conclusions Several factors of oligometastases and SBRT affected LC. LC of pulmonary oligometastases by SBRT showed a significant survival benefit compared to patients with local failure.

With the newly-developed static-port forward-planning (FP) mode of tomotherapy, the ratio of the dose of the planning target volume (PTV) periphery to the maximum dose can be easily adjusted by modifying leaf margins when planning stereotactic body radiotherapy (SBRT). The purpose of this study was to evaluate the characteristics of FP plans compared to helical intensity-modulated radiotherapy (IMRT) and helical 3D conformal radiotherapy (3DCRT) plans of SBRT for lung tumors. The three plans were created for 14 tumors in 11 patients. For 13 tumors, 60 Gy in 7.5-Gy fractions was prescribed for a minimum coverage dose of 95% of the PTV (D95). The prescribed isodose line (PIL) was intended to be 60–80% of the maximum dose. Nine angles were used for the FP plans. The median D98 and D50 of the internal target volume for FP, helical-IMRT and helical-3DCRT plans were 70.4, 71.4 and 60.5 Gy, respectively (P

Background Successful local therapy for oligometastases may lead to longer survival. The purpose of this multicenter retrospective study was to investigate the effectiveness of stereotactic body radiotherapy (SBRT) for pulmonary oligometastases and to investigate affecting factors for local control (LC). Methods The inclusion criteria was that SBRT for pulmonary oligometastases was the number of metastases was limited to 1 to 5, the primary lesion and other extrathoracic metastases were controlled before SBRT, and the biological effective dose (BED10) of SBRT was 75 Gy or more. The Cox proportional hazards model was used for analyses. Results Data for 1378 patients with 1547 tumors from 68 institutions were analyzed. The median follow-up period was 24.2 months. One-year, 3-year and 5-year LC rates were 92.1%, 81.3% and 78.6%, respectively, and 1-year, 3-year and 5-year overall survival rates were 90.1%, 60.3% and 45.5%, respectively. Multivariate analysis for LC showed that increased maximum tumor diameter (p = 0.011), type A dose calculation algorithm (p = 0.005), shorter overall treatment time of SBRT (p = 0.035) and colorectal primary origin (p

Background and purpose The rate of oncologic pulmonary death after stereotactic body radiotherapy for pulmonary oligometastases has never been reported. The purpose of current study was to investigate the rate of freedom from oncologic pulmonary death (FOPD) and to analyze factors affecting for FOPD. Materials and methods The inclusion criteria for this retrospective study were that SBRT was performed between 2004 and 2015, the number of metastases was 5 or less, the primary lesion and extrathoracic metastases needed to be controlled before SBRT and a biological effective dose (BED10) of 75 Gy or more was needed. The Kaplan–Meier estimator and the log-rank test were used to calculate and compare the stratified rates of FOPD. The Cox proportional hazards model was used for multivariate analyses (MVA). Primary disease death from a non-oncologic pulmonary cause was censored in model 1 and was excluded in model 2. Results A total of 1172 patients with 1315 tumors were enrolled. During a median follow-up period of 24.5 months, oncologic pulmonary deaths accounted for 101 of 221 primary disease deaths. The 1-year, 3-year and 5-year FOPD rates in model 1 were 98.2%, 89.4% and 84.0%, respectively. MVA for FOPD revealed that local failure of the irradiated tumor, squamous cell carcinoma pathology, and chemotherapy after SBRT had significant relationships with lower FOPD rates in both model 1 and model 2. Conclusions Successful local control of pulmonary oligometastases by SBRT contributed to a higher FOPD rate.

AIM We aimed to identify the optimal candidates for early salvage radiotherapy (SRT) among patients with biochemical recurrence (BCR) after radical prostatectomy (RP). METHODS This multi-institutional retrospective study included 371 patients treated using SRT after RP. The median (range) PSA level at BCR was 0.36 (0.10-2.00) ng/mL. The association between early SRT (ie, starting PSA level

The safety and efficacy of dose-escalated radiotherapy with intensity-modulated radiotherapy (IMRT) and image-guided radiotherapy (IGRT) remain unclear in salvage radiotherapy (SRT) after radical prostatectomy. We examined the impact of these advanced radiotherapy techniques and dose intensification on the toxicity of SRT. This multi-institutional retrospective study included 421 patients who underwent SRT at the median dose of 66 Gy in 2-Gy fractions. IMRT and IGRT were used for 225 (53%) and 321 (76%) patients, respectively. At the median follow-up of 50 months, the cumulative incidence of late grade 2 or higher gastrointestinal (GI) and genitourinary (GU) toxicities was 4.8% and 24%, respectively. Multivariate analysis revealed that the non-use of either IMRT or IGRT, or both (hazard ratio [HR] 3.1, 95% confidence interval [CI] 1.8–5.4, p p = 0.048) were associated with late GI toxicity, whereas a higher dose ≥68 Gy was the only factor associated with GU toxicities (HR 3.1, CI 1.3–7.4, p = 0.012). This study suggested that the incidence of GI toxicities can be reduced by IMRT and IGRT in SRT, whereas dose intensification may increase GU toxicity even with these advanced techniques.

Background Cutaneous adverse reactions are frequently induced by mogamulizumab. Cases of Stevens-Johnson syndrome, toxic epidermal necrolysis and severe photosensitivity related to mogamulizumab have been reported. This study investigated whether severe radiation-induced dermatitis occurred in patients undergoing radiotherapy after the administration of mogamulizumab for adult T-cell leukaemia/lymphoma. Methods We retrospectively reviewed 46 courses of radiotherapy administered to 15 consecutive patients with adult T-cell leukaemia/lymphoma (acute, n = 7; lymphoma, n = 7; smouldering, n = 1) who received mogamulizumab before or during radiotherapy at three institutions between 2012 and 2017. Results During 43 of the 46 radiotherapy courses, patients developed Grade ≤1 radiation-induced dermatitis. No patient developed Grade ≥3 radiation-induced dermatitis. No patient was prescribed ointments as prophylactic treatment for radiation-induced dermatitis. Development of radiation-induced dermatitis was not significantly associated with the number of days since the administration of mogamulizumab prior to radiotherapy (P = 0.85), frequency of administration of mogamulizumab before/during radiotherapy (P = 0.33), administration of mogamulizumab during radiotherapy (P = 0.41) or types of lesions in adult T-cell leukaemia/lymphoma cases (cutaneous vs. non-cutaneous, P = 0.74). Development of radiation-induced dermatitis was significantly related to the total cutaneous dose (mean, 31.9 Gy [95% confidence interval: 26.6-37.1 Gy] vs. 19.7 Gy [95% confidence interval: 16.2-23.2 Gy], P = 0.0004) and total prescribed dose (mean, 31.5 Gy [95% confidence interval: 26.2-36.8 Gy] vs. 18.5 Gy [95% confidence interval: 15.0-22.0 Gy], P = 0.0002). Conclusion None of the 15 patients who received moderate-dose radiotherapy developed severe radiation-induced dermatitis during the 46 courses of radiotherapy after mogamulizumab administration.

Definitive radiotherapy is an important alternative treatment for meningioma patients who are inoperable or refuse surgery. We evaluated the efficacy and toxicity of CyberKnife-based stereotactic radiosurgery (SRS) and hypofractionated stereotactic radiotherapy (hSRT) as first-line treatments for intracranial meningiomas that were diagnosed using magnetic resonance imaging (MRI) and/or computed tomography (CT). Between February 2005 and September 2015, 41 patients with intracranial meningiomas were treated with CyberKnife-based SRS or hSRT. Eleven of those tumors were located in the skull base. The median tumor volume was 10.4 ml (range, 1.4–56.9 ml). The median prescribed radiation dose was 17 Gy (range, 13–20 Gy to the 61–88% isodose line) for SRS (n = 9) and 25 Gy (range, 14–38 Gy to the 44–83% isodose line) for hSRT (n = 32). The hSRT doses were delivered in 2 to 10 daily fractions. The median follow-up period was 49 months (range, 7–138). The 5-year progression-free survival rate (PFS) for all 41 patients was 86%. The 3-year PFS was 69% for the 14 patients with tumor volumes of ≥13.5 ml (30 mm in diameter) and 100% for the 27 patients with tumor volumes of 2 toxicities were observed in 5 patients (all of them had tumor volumes of ≥13.5 ml). SRS and hSRT are safe and effective against relatively small (

OBJECTIVE This study evaluated the clinical feasibility of a new low-cost TomoTherapy system (OnradTM) and compared it with low-cost linear accelerator models (linacs). METHODS Various aspects of treatment and cost were compared between Onrad and linacs for 3-dimensional radiotherapy (3DCRT). Dosimetric comparisons of 10 patients each with breast, stage III lung, prostate, head and neck, and cervical cancers were carried out (total 100 plans). RESULTS Onrad had advantages in terms of availability of long treatment fields and a smaller mechanical footprint. For breast cancers and lung cancers, target dose homogeneity in Onrad plans was better than that in 3DCRT. In the prostate plans, Onrad plans provided superior D95, conformity and homogeneity. The rectum doses of Onrad plans were lower than those with 3DCRT. Onrad plans provided superior homogeneity and D95 in head and neck cancer. The mean dose and V10-40 Gy of the parotid glands was lower using Onrad. In the cervical cancer plans, target doses were similar with both systems. Normal tissue doses were equal. CONCLUSIONS Onrad is useful in the clinical setting. Onrad can achieve favorable or comparable dose distributions compared with those of 3DCRT in actual clinical treatment of breast, lung, prostate, head and neck, and cervical cancers.

Background To treat multiple targets separated in the craniocaudal direction within a short time, we invented a new technique using multiple static‐port tomotherapy with the dynamic‐jaw mode and named it the pseudo‐DJDC (pDJDC) technique. We compared the pDJDC plans and helical tomotherapy plans using the dynamic‐jaw mode (HDJ) for multiple targets. In the pDJDC plans, we used a beam set with 2–7 ports to the targets at the same level in the craniocaudal direction, and employed another beam set for other targets using different port angles (9–12 angles in total). Methods In seven patients, two plans using the pDJDC and HDJ techniques were compared. For multiple targets (n = 2–6), 20–60 Gy in 2‐ to 7.5‐Gy fractions were prescribed for the planning target volumes at D50%. The conformity index, uniformity index (D5%/D95%), dose distribution in the lung, and treatment time were evaluated. Results The median conformity index of all seven patients was 3.0 for the pDJDC plans and 2.4 for the HDJ plans (P = 0.031). The median uniformity indices of the planning target volume (n = 25) for the two plans were 1.048 and 1.057, respectively (P = 0.10). For five patients with thoracic targets, the median mean lung doses were 2.6 Gy and 2.4 Gy, respectively (P = 0.63). The median V5Gy and V20Gy of the lungs in the five patients were 11.8% and 8.5% (P = 0.63), and 1.6% and 2.1% (P = 0.31), respectively. The pDJDC plans reduced the treatment time by 48% compared to the HDJ plans (median: 462 and 884 sec, respectively, P = 0.031). Conclusion The pDJDC technique allows treatment of multiple targets in almost half the time of the HDJ technique. The pDJDC plans were comparable to the HDJ plans in dose distribution, although the conformity index deteriorated.

AIM This study was performed to confirm the superior overall survival (OS) after pulmonary oligo-recurrence compared to pulmonary sync-oligometastases in a large nationwide study. PATIENTS AND METHODS Patients that met the following criteria were included: 1 to 5 lung-only metastases at the beginning of stereotactic body radiation therapy (SBRT) was performed between January 2004 and June 2015, and the biological effective dose (BED) of SBRT was 75 Gy or more. The parameters included in the analyses were age, gender, ECOG PS, primary lesion, pathology, oligoetastatic state, SBRT date, chemotherapy before SBRT, chemotherapy concurrent SBRT, chemotherapy after SBRT, maximum tumor diameter, number of metastases, field coplanarity, dose prescription, BED10, OTT of SBRT. RESULTS In total, 1,378 patients with 1,547 tumors were enrolled. Oligo-recurrence occurred in 1,016 patients, sync-oligometastases in 118, and unclassified oligometastases in 121. The three-year OS was 64.0% for oligo-recurrence and 47.5% for sync-oligometastasis (p

A previous study showed that continuous low-dose-rate irradiation promoted the growth of silkworm larvae. This study aimed to confirm that finding, determine the optimal dose rate for growth promotion, and compare low- and high-dose-rate irradiation in silkworms, while also investigating the effects of the radiation-emitting sheet on growth and tumor transplantability in mice. Silkworm eggs were placed on low-dose-emitting sheets with 4 different dose rates (γ-ray rate: 1.7 -22.4 μSv/hour) or on control sheets. The other groups of silkworm larvae received single whole-body X-irradiation (0.1-50 Gy), and subsequent body weight changes were monitored. Starting at 3 weeks old, Balb/c mice were bred on the same sheets, and body weight change was measured. Seven weeks later, the mice were used to investigate the transplantability of EMT6 tumor cells cultured in vitro. The silkworms bred on the 13.4- and 22.4-μSv/hour sheets became larger than the control. Single 50-Gy irradiation suppressed the growth of silkworms. An increase in the time to EMT6 tumor development was observed in low-dose-rate-irradiated mice. This study confirmed growth promotion of silkworms by continuous low-dose radiation and demonstrated growth suppression at a high dose rate. Growth promotion was not observed in mice; further studies using higher dose-rate sheets may be warranted.

The optimal treatment for hilar or mediastinal lymph node (LN) recurrence developing after stereotactic body radiotherapy (SBRT) for stage I non-small cell lung cancer remains unclear. This study evaluated 5-year results of radiotherapy in such patients in comparison with those for postoperative LN metastases. Between 2004 and 2013, 27 patients with hilar and/or mediastinal LN metastases without local recurrence and distant metastasis after SBRT (n = 14) or surgery (n = 13) were treated with definitive conventional radiotherapy. The median total dose for treating metastatic LN was 60 Gy for the post-SBRT group and 66 Gy for the post-surgery group. The median follow-up for the 5 surviving patients was 62 months. The overall survival, cause-specific survival, progression-free survival, and local control rates at 5 years after mediastinal irradiation were 14%, 45%, 21%, and 58%, respectively, for the 14 patients in the post-SBRT group. These rates were 36%, 45%, 39%, and 92%, respectively for the post-surgery group (p = 0.066, 0.64, 0.38, and 0.41, respectively). Four patients in the post-SBRT group survived 3 or more years (range 36–92 months) after mediastinal irradiation. A proportion of patients in both groups achieved long-term survival by conventional radiotherapy.

The purpose of this study was to evaluate differences in parameters of diffusion kurtosis imaging (DKI) and minimum apparent diffusion coefficient (ADCmin) between benign and malignant musculoskeletal tumors. In this prospective study, 43 patients were scanned using a DKI protocol on a 3-T MR scanner. Eligibility criteria were: non-fatty, non-cystic soft tissue or osteolytic tumors; > 2 cm; location in the retroperitoneum, pelvis, leg, or neck; and no prior treatment. They were clinically or histologically diagnosed as benign (n = 27) or malignant (n = 16). In the DKI protocol, diffusion-weighted imaging was performed using four b values (0-2000 s/mm2) and 21 diffusion directions. Mean kurtosis (MK) values were calculated on the MR console. A recently developed software application enabling reliable calculation was used for DKI analysis. MK showed a strong correction with ADCmin (Spearman’s rs = 0.95). Both MK and ADCmin values differed between benign and malignant tumors (p

Despite insufficient laboratory data, radiotherapy after intratumoral injection of hydrogen peroxide (H2 O2 ) is increasingly being used clinically for radioresistant tumors. Especially, this treatment might become an alternative definitive treatment for early and advanced breast cancer in patients who refuse any type of surgery. The purpose of this study was to investigate the biological effects and appropriate combination methods of irradiation and H2 O2 in vivo. SCCVII tumor cells transplanted into the legs of C3H/HeN mice were used. Chronological changes of intratumoral distribution of oxygen bubbles after injection of H2 O2 were investigated using computed tomography. The effects of H2 O2 alone and in combination with single or five-fraction irradiation were investigated using a growth delay assay. The optimal timing of H2 O2 injection was investigated. Immunostaining of tumors was performed using the hypoxia marker pimonidazole. Oxygen bubbles decreased gradually and almost disappeared after 24 h. Administration of H2 O2 produced 2-3 days' tumor growth delay. Tumor regrowth was slowed further when H2 O2 was injected before irradiation. The group irradiated immediately after H2 O2 injection showed the longest tumor growth delay. Dose-modifying factors were 1.7-2.0 when combined with single irradiation and 1.3-1.5 with fractionated irradiation. Pimonidazole staining was weaker in tumors injected with H2 O2 . H2 O2 injection alone had modest antitumor effects. Greater tumor growth delays were demonstrated by combining irradiation and H2 O2 injection. The results of the present study could serve as a basis for evaluating results of various clinical studies on this treatment.

The recently developed dynamic jaw technology of tomotherapy can reduce craniocaudal dose spread without much prolonging the treatment time. This study aimed to investigate the efficacy of the dynamic jaw mode for tomotherapy of breast cancer. Static tomotherapy plans of the whole breast and supraclavicular regional lymph nodes, and plans for the whole breast only were generated in 25 patients with left-sided breast cancer. Plans with a field width of 2.5 or 5 cm with the dynamic or fixed jaw modes were made for each patient. The prescribed dose was 50 Gy in 25 fractions. In whole breast and supraclavicular nodal radiotherapy, dose distributions and homogeneity of the planning target volume (PTV) with the dynamic jaw mode were slightly inferior to those with the fixed jaw mode with a 5-cm field width (P < .05). However, lung low-dose volumes and mean doses of the larynx, thyroid, skin, and all the healthy tissues combined were smaller with the dynamic jaw mode than with the fixed jaw mode with a 5-cm field width (P < .001). In whole breast radiotherapy, mean doses of the skin and healthy tissues were lower with the dynamic jaw mode than with the fixed jaw mode with a 5-cm field width (P < .001) without significant differences in PTV dose distributions, homogeneity, and conformity. The dynamic jaw mode provided better sparing of organs at risks with minimal disturbance of dose–volume indices of PTV. Considering the treatment time, the 5-cm-field dynamic jaw mode is more efficient than the 2.5-cm fixed jaw mode.

With the newly developed dynamic jaws technology, radiation dose for the cranio-caudal edges of a target can be lowered in the treatment with tomotherapy. We compared dynamic-jaw- and fixed-jaw-mode plans for lung cancer. In 35 patients, four plans using the 2.5-cm dynamic-, 2.5-cm fixed-, 5.0-cm dynamic-, and 5.0-cm fixed-jaw modes were generated. For 10 patients with upper lobe stage I lung cancer, the helical tomotherapy mode was used. Fifty-six Gy in 8 fractions was prescribed as a minimum coverage dose for 95% of the target (D95%). For 25 patients with locally advanced lung cancer, plans using four static ports (TomoDirect® mode) were made. Sixty Gy in 30 daily fractions for the primary tumor and swollen lymph nodes and 51 Gy in 30 fractions for prophylactic lymph node areas were prescribed as median doses. The mean conformity index of the planning target volume were similar among the four plans. The mean V5 Gy of the lung for 2.5-cm dynamic-, 2.5-cm fixed-, 5.0-cm dynamic-, and 5.0-cm fixed-jaw mode plans were 18.5%, 21.8%, 20.1%, and 29.4%, respectively ( p < 0.0001), for patients with stage I lung cancer, and 37.3%, 38.7%, 40.4%, and 44.0%, respectively ( p < 0.0001), for patients with locally advanced lung cancer. The mean V5 Gy of the whole body was 1,826, 2,143, 1,983, and 2,939 ml, respectively ( p < 0.0001), for patients with stage I lung cancer and 4,849, 5,197, 5,220, and 6,154 ml, respectively ( p < 0.0001), for patients with locally advanced lung cancer. Treatment time was reduced by 21-39% in 5.0-cm dynamic-jaw plans compared to 2.5-cm plans. Regarding dose distribution, 2.5-cm dynamic-jaw plans were the best, and 5.0-cm dynamic-jaw plans were comparable to 2.5-cm fixed-jaw plans with shorter treatment times. The dynamic-jaw mode should be used instead of the conventional fixed-jaw mode in tomotherapy for lung cancer.

Outcomes of three protocols of intensity-modulated radiation therapy (IMRT) for localized prostate cancer were evaluated. A total of 259 patients treated with 5-field IMRT between 2005 and 2011 were analyzed. First, 74 patients were treated with a daily fraction of 2.0 Gy to a total of 74 Gy (low risk) or 78 Gy (intermediate or high risk). Then, 101 patients were treated with a 2.1-Gy daily fraction to 73.5 or 77.7 Gy. More recently, 84 patients were treated with a 2.2-Gy fraction to 72.6 or 74.8 Gy. The median patient age was 70 years (range, 54-82) and the follow-up period for living patients was 47 months (range, 18-97). Androgen deprivation therapy was given according to patient risk. The overall and biochemical failure-free survival rates were, respectively, 96 and 82% at 6 years in the 2.0-Gy group, 99 and 96% at 4 years in the 2.1-Gy group, and 99 and 96% at 2 years in the 2.2-Gy group. The biochemical failure-free rate for high-risk patients in all groups was 89% at 4 years. Incidences of Grade ≥ 2 acute genitourinary toxicities were 9.5% in the 2.0-Gy group, 18% in the 2.1-Gy group, and 15% in the 2.2-Gy group (P = 0.29). Cumulative incidences of Grade ≥ 2 late gastrointestinal toxicity were 13% in the 2.0-Gy group at 6 years, 12% in the 2.1-Gy group at 4 years, and 3.7% in the 2.2-Gy group at 2 years (P = 0.23). So far, this stepwise shortening of treatment periods seems to be successful.

Recurrent ependymomas were retreated with stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT). The efficacy, toxicities, and differences between SRS and FSRT were analyzed.Eight patients with recurrent ependymomas fulfilling the criteria described below were evaluated. Inclusion criteria were: (1) the patient had previously undergone surgery and conventional radiotherapy as first-line treatment; (2) targets were located in or adjacent to the eloquent area or were deep-seated; and (3) the previously irradiated volume overlapped the target lesion.FSRT was delivered to 18 lesions, SRS to 20 lesions. A median follow-up period was 23 months. The local control rate was 76 % at 3 years. No significant differences in local control were observed due to tumor size or fractionation schedule. Lesions receiving25 Gy/5 fr or 21 Gy/3 fr did not recur within 1 year, whereas no dose-response relationship was observed in those treated with SRS. No grade ≥2 toxicity was observed.Our treatment protocol provided an acceptable LC rate and minimal toxicities. Because local recurrence of tumors may result in patient death, a minimum dose of 21 Gy/3 fr or 25 Gy/5 fr or higher may be most suitable for treatment of these cases.