BACKGROUND International guidelines recommend brachytherapy for patients with dysphagia from esophageal cancer, whereas brachytherapy is infrequently used to palliate dysphagia in some countries. To clarify the availability of palliative treatment for dysphagia from esophageal cancer and explain why brachytherapy is not routinely performed are unknown, this study investigated the use of brachytherapy and external beam radiotherapy for dysphagia from esophageal cancer. METHODS Japanese Radiation Oncology Study Group members completed a survey and selected the treatment that they would recommend for hypothetical cases of dysphagia from esophageal cancer. RESULTS Of the 136 invited facilities, 61 completed the survey (44.9%). Four (6.6%) facilities performed brachytherapy of the esophagus, whereas brachytherapy represented the first-line treatment at three (4.9%) facilities. Conversely, external beam radiotherapy alone and chemoradiotherapy were first-line treatments at 61 and 58 (95.1%) facilities, respectively. In facilities that performed brachytherapy, the main reason why brachytherapy of the esophagus was not performed was high invasiveness (30.2%). Definitive-dose chemoradiotherapy with (≥50 Gy) tended to be used in patients with expected long-term survival. CONCLUSIONS Few facilities routinely considered brachytherapy for the treatment of dysphagia from esophageal cancer in Japan. Conversely, most facilities routinely considered external beam radiotherapy. In the future, it will be necessary to optimize external beam radiotherapy.

Abstract Evidence regarding postoperative radiation therapy (PORT) for metastases to the long bones is lacking. Characterizing the current practice patterns and identifying factors that influence dose-fractionation schedules are essential for future clinical trials. An internet-based survey of the palliative RT subgroup of the Japanese Radiation Oncology Study Group was performed in 2017 to collect data regarding PORT prescription practices and dose-fractionation schedules. Responders were also asked to recommend dose-fractionation schedules for four hypothetical cases that involved a patient with impending pathological fractures and one of four clinical features (poor prognosis, solitary metastasis, radio-resistant primary tumor or expected long-term survival). Responders were asked to indicate their preferred irradiation fields and the reasons for the dose fractionation schedule they chose. Responses were obtained from 89 radiation oncologists (67 institutions and 151 RT plans) who used 22 dose-fractionation schedules, with the most commonly used and recommended schedule being 30 Gy in 10 fractions. Local control was the most common reason for preferring longer-course RT. High-dose fractionated schedules were preferred for oligometastasis, and low-dose regimens were preferred for patients with a poor prognosis; however, single-fraction RT was not preferred. Most respondents recommended targeting the entire orthopedic prosthesis. These results indicated that PORT using 30 Gy in 10 fractions to the entire orthopedic prosthesis is preferred in current Japanese practice and that single-fraction RT was not preferred. Oligometastasis and poor prognosis influenced the selection of high- or low-dose regimens.

PurposeTo predict local recurrence (LR) and distant metastasis (DM) in early stage non‐small cell lung cancer (NSCLC) patients after stereotactic body radiotherapy (SBRT) in multiple institutions using breath‐hold computed tomography (CT)‐based radiomic features with random survival forest.MethodsA total of 573 primary early stage NSCLC patients who underwent SBRT between January 2006 and March 2016 and met the eligibility criteria were included in this study. Patients were divided into two datasets: training (464 patients in 10 institutions) and test (109 patients in one institution) datasets. A total of 944 radiomic features were extracted from manually segmented gross tumor volumes (GTVs). Feature selection was performed by analyzing inter‐segmentation reproducibility, GTV correlation, and inter‐feature redundancy. Nine clinical factors, including histology and GTV size, were also used. Three prognostic models (clinical, radiomic, and combined) for LR and DM were constructed using random survival forest (RSF) to deal with total death as a competing risk in the training dataset. Robust models with optimal hyper‐parameters were determined using fivefold cross‐validation. The patients were dichotomized into two groups based on the median value of the patient‐specific risk scores (high‐ and low‐risk score groups). Gray's test was used to evaluate the statistical significance between the two risk score groups. The prognostic power was evaluated by the concordance index with the 95% confidence intervals (CI) via bootstrapping (2000 iterations).ResultsThe concordance indices at 3 yr of clinical, radiomic, and combined models for LR were 0.57 [CI: 0.39–0.75], 0.55 [CI: 0.38–0.73], and 0.61 [CI: 0.43–0.78], respectively, whereas those for DM were 0.59 [CI: 0.54–0.79], 0.67 [CI: 0.54–0.79], and 0.68 [CI: 0.55–0.81], respectively, in the test dataset. The combined DM model significantly discriminated its cumulative incidence between high‐ and low‐risk score groups (P < 0.05). The variable importance of RSF in the combined model for DM indicated that two radiomic features were more important than other clinical factors. The feature maps generated on the basis of the most important radiomic feature had visual difference between high‐ and low‐risk score groups.ConclusionsThe radiomics approach with RSF for competing risks using breath‐hold CT‐based radiomic features might predict DM in early stage NSCLC patients who underwent SBRT although that may not have potential to predict LR.

Although postoperative radiation therapy (RT) (PORT) for patients with long bone metastases has become common, reliable evidence is lacking. The optimal dose fractionation and irradiation field of PORT are unknown. This study aimed to characterize current patterns of practice regarding PORT and factors that affect dose fractionation. Members of the Japanese Radiation Oncology Study Group (JROSG) completed an internet-based survey. The survey was composed of questions to determine the prescription of various dose fractionations in each institution in 2017, describe dose fractionations in four hypothetical cases in which patients were treated with PORT for impending pathological fractures in a lower limb, and indicate irradiation fields each member would prefer. Case 1 was a patient with limited prognosis of non-small-cell lung cancer. Case 2 was a patient with a single oligometastasis. Case 3 was identical to case 1, except for the presence of a radio-resistant primary tumor, renal cell carcinoma. Case 4 was a patient with breast cancer with expected long-term prognosis. Radiation oncologists who recommended long-course RT in case 1 were asked to explain why they considered long-course RT over short-course RT (i.e., 8 Gy in 1 fraction or 20 Gy in 5 fractions). In total, 89 radiation oncologists from 68 institutions (50% of JROSG institutions) responded. Of the patients treated at these institutions, 151 were eligible for this study, except for 1 patient with an unknown prescribed dose fractionation. Among 22 different dose fractionations prescribed, the most common was 30 Gy in 10 fractions (n=75; 50%), followed by 20 Gy in 5 fractions (n=29; 19%). In all the hypothetical cases, the commonest prescribed regimen was 30 Gy in 10 fractions. For case 1, short-course RT (i.e., 8 Gy in 1 fraction or 20 Gy in 5 fractions) was preferred by 20% of the respondents (n=18). The following factors were most often cited as reasons for preferring long-course RT（i.e., >20 Gy in 5 fractions）: “local control” (54%), “incidence of re-irradiation” (34%), and “time until first increase in pain” (19%). Zero percent of the respondents for case 2, 8% for case 3, and 5% for case 4 prescribed short-course RT. Fractionated dose regimens of >30 Gy in 10 fractions were preferred in patients with oligometastasis (53%) compared to those with radio-resistant tumors (34%) and those with expected long-term prognosis (25%). For the irradiation field, 74% (n=66) of respondents recommended involvement of “the entire orthopedic prosthesis” for PORT. For PORT of long bone metastases, 30 Gy in 10 fractions for the entire orthopedic prosthesis is preferred currently in Japan. Higher dose regimens are preferred for patients with oligometastasis. Our results will guide the designing future clinical trials or research for bone metastases.

Abstract The aim of this study was to survey the current status of reirradiation (Re-RT) and patterns of practice in Japan. An email questionnaire was sent to Kansai Cancer Therapist Group partner institutions, using questions similar to those in the Canadian radiation oncologist (RO) survey (2008). A total of 34 ROs from 28 institutions returned the survey. All 28 institutions experienced Re-RT cases in 2014. However, 26 of the 28 institutions (93%) reported difficulty in obtaining Re-RT case information from their respective databases. Responses from 19 institutions included the number of Re-RT cases; this rose from 183 in the period 2005–2009 (institution median = 4; 2–12.9) to 562 in the period 2010–2014 (institution median = 26; 2–225). Important considerations for indication of Re-RT were age (65%), performance status (83%), life expectancy (70%), absence of distant metastases (67%), and interval since previous treatment (73%). Previous total radiation dose (48%), volume of tissue irradiated (72%), and the biologically equivalent dose (BED; 68.5%) were taken into account during Re-RT planning. These factors were similar to those considered in the Canadian survey; however, the present study did not consider age. In eight site-specific scenarios, barring central nervous system recurrence, more than 90% of ROs agreed to perform Re-RT, which was higher than the percentage observed in the Canadian survey. Re-RT cases have increased in number and aroused interest among ROs in this decade of advanced technology. However, consensus building to establish guidelines for the practice and prospective evaluation of Re-RT is required.

260 Background: Patient-reported experiences of cancer care are an important outcome of cancer control programs. To establish a nation-wide system to monitor progress in cancer control policies, we piloted a patient experience survey to six hospitals in Japan. Methods: We conducted a self-administered questionnaire survey to a total of 1,804 adult cancer patients receiving cancer treatment in six hospitals (three cancer centers, two general hospitals, and one academic institution) from July 2013 to Mar 2014. Patients were asked to answer 94 questions covering eight dimensions of cancer experience: 1) decision-making, 2) care coordination, 3) patient education, 4) pain control, 5) emotional support, 6) family support, 7) access to care, and 8) care continuity. Results: Eighty percent of the patients reported that their treatment preferences were respected in the decision-making process, but a large proportion of patients (60%) also noted that they preferred to have their treatment decisions made for them by their physicians. Many (32%) expressed difficulty in communicating their questions and concerns to their physicians at the time of diagnosis. Only one fifth of patients were informed at the time of diagnosis that they can seek for a second opinion from other providers. Average patient-reported wait time to surgery was 30 days, which was considered to be long by a third of the patients. Eighty percent of patients felt that their care was well-coordinated by a multidisciplinary team, while % also felt that they received adequate emotional support from their medical staff. Relatively small proportion of outpatients (77%) felt that they had access to medical staff when they had medical questions, compared to nearly all patients in an inpatient setting. Only 65% of inpatients and 40% of outpatients felt that they had received best available pain control during their care. Less than half of the patients were able to communicate their preferred place of care after discharge with their healthcare provider. Conclusions: Patient-reported experiences of cancer care are an important outcome measure of cancer policy performance. This pilot study served to reveal some of the important on in future nationwide surveys.

Dynamic MLC log files are recorded when intensity modulated radiation therapy(IMRT) irradiation is completed. These files are not information about irradiated dose, but only a report of the MLC position at each dose segment. To acquire the error of irradiated dose is important from the quality assurance (QA) point of view. The purpose of this study is to develop a program to estimate the error of irradiated dose by analyzing MLC log files and verify their calculation accuracy. First, we measured doses of sliding slit fields with the leaf gap of 12 types (3 - 100 mm) which set the gap error of 12 types (-1.0 - +2.0 mm) respectively. To obtain a graph that indicates the relationship between the gap error and the dose error, we determined a conversion function from its approximation curve. Second, the leaf gap and the gap error at each dose segment were calculated from analyzing the MLC log files. From these data, the program that calculates the errors of estimating irradiated dose from the MLC log files was created. Finally, to verify the calculation accuracy, we compared the calculated errors with the measured errors using sliding slit fields with the leaf gap of eight types (3 - 100 mm) which set the monitor unit of six types (10 - 200 MU) respectively. The conversion function from the approximation curve showed better agreement to the original curve in the case of the leaf gap of 50 mm or less. In the sliding slit fields measurement, the irradiated dose error between the calculated and the measured were -1.61% to +2.37% in the leaf gap of 50 mm or less, and were -0.26% to +11.35% in the leaf gap of 50 mm or over. Because of an approximation error of the conversion function, there was a trend that the larger the leaf gap, the larger the dose error in the leaf gap of 50 mm or over. Furthermore, in every leaf gap, the lower the MU in which the beam hold-off frequently occurs, the larger the error. Most prostate IMRT plans in our institution have approximately 20 mm of the mean leaf gap and have no influence on low MU because the beam hold-off hardly occurs in these irradiations. Therefore, this program that converts the error of the leaf position to the estimate error of irradiated dose has sufficient accuracy in the leaf gap of 50 mm or less, and is considered to be a useful QA tool for estimating the irradiated dose error for the standard prostate IMRT in our institution.

To report the results of radiation therapy with concurrent intermittent arterial chemotherapy using a reservoir for muscle-invasive bladder cancer. From Apr. 1997 to Sep. 2006, we analyzed the clinical results of 11 patients (8 males and 3 females), ranged in age 61∼83 (mean 78 years,). All 11 patients had urothelial cancer. The TNM classifications were with T stage; T1b: 1, T2a: 5, T2b: 2, T3a: 1, T4a: 2. All were classified N0 M0. Pathologic grades were G2 in 5 patients and G3 in 6. The nonsurgical reason was due to advanced age in 5 patients, refusal of surgery in 5 and multiple primary cancers in 1. In prior to treatment, arterial blood supply was altered by coil embolizations to one vessel for bladder. The contralateral internal iliac artery and the ipsilateral superior gluteal artery were embolized by coil, and the tip of catheter was fixed inside the superior gluteal artery and side hole of the catheter was indwelled into the internal iliac artery. Then, a reservoir was placed in a lower abdominal wall subcutaneous pocket. Irradiation was limited to the bladder using four opposed field techniques with 2 Gy x 25 = 50 Gy. In the meantime, 10mg/body ia THP on the days 2,9,16 and 23 and 20mg/body ia CDDP on the days 3, 10, 17, 24 were administered concurrently through the reservoir. The follow-up period ranged from 17 to 117 months. All patients achieved a CR due to the initial treatment. Only 2 of 11 patients had local recurrence: one treated with TUR-Bt, and the other became invasive after TUR-Bt and underwent total cystectomy. Consequently, 2 of 2 patients who had local recurrence were salvaged. Although only minor acute side-effects (microhematuria) was found, this was thought to be the late side-effects due to the deterioration of the contracted bladder caused by the precedent TUR-Bt. The following two complications caused by the intra-arterial chemotherapy were found: the reservoir was removed due to infection after treatment in one patient. In another, because of the positive cytology one month after treatment, COMPA chemotherapy was intended to add optional treatment, but perianal burning sensation and skin ulcer were appeared, probably caused by the recanalization of the embolized vessel. This resulted in the halt of treatment, but obtained a CR. Distant metastasis was found in three patients. Disease-specific death was seen in two patients, intercurrent-disease death in two, disease-free survivor in six and being alive with cancer in one. These findings suggest that radiation therapy with concurrent arterial chemotherapy for invasive bladder cancer produces an excellent local effect with less side effects. This therapy could be an alternative to bladder-preservation treatment.

PURPOSE:To characterize inter- and intra-individual differences in X-ray-induced DNA strand break rejoining kinetics in human peripheral white blood cells (WBC) obtained from 10 healthy volunteers.MATERIALS AND METHODS:The alkaline and neutral versions of the comet assay were used to measure the rate of rejoining of predominantly single-strand breaks (ssb) following exposure to 8 Gy and double-strand breaks (dsb) following 75 Gy.RESULTS:All cells within a population responded in a similar fashion to induction of ssb and dsb; however, a subset of the WBC appeared to rejoin ssb more rapidly. For the 10 individuals examined, the percentage of ssb rejoined by the rapid component(s) was 47 +/- 16% and the rejoining half-time for the slow component was 1.3 +/- 0.4 h. By 24 h after 8 Gy, 4.9 +/- 3.8% of the initial ssb remained. For dsb rejoining, 58 +/- 11% of the initial damage was still present 4h after 75 Gy and by 24 h 32% of the initial level of damage was still detected. Heavily damaged cells present 24 h after 75 Gy varied from 4% to 50% and were excluded from the analysis of repair rates.CONCLUSIONS:Inter-individual variability exceeded intra-individual variability for 2 of 4 endpoints examined for ssb repair, but not for dsb repair. It was concluded that DNA damage measured using the comet assay could identify a range in the X-ray repair responses of WBC from different normal individuals. Whether these differences correlate with differences in cell killing by radiation remains to be determined.

The authors analyzed the radiation dose to the periphery of the cervix and area of the cervix in relation to local failure of radiotherapy for carcinoma of the cervix using computed tomography (CT) images.

The repair of slowly repairing potentially lethal damage (PLD) in radiosensitive cells from the severe combined immunodeficient (scid) mouse was compared with that in Balb/c 3T3 cells with "wild-type" radiosensitivity and that in RD13B2 cells derived from scid cells whose sensitivity is normal because of the presence of fragments of human chromosome 8. Treatment with 0.23 M NaCl was used for fixation of slowly repairing PLD. The scid cells repaired PLD sensitive to 0.23 M NaCl to a great extent whin 3-4 h, similarly to Balb/c 3T3 and RD13B2 cells. This indicates that the scid mutation hardly affects the repair of PLD sensitive to 0.23 M NaCl. On the other hand, as reported previously, the rapidly repairing PLD that is sensitive to 0.5 M NaCl was repaired only slowly (3-4 h) in scid cells, in contrast to the rapid repair (within 1 h) seen with Balb/c 3T3 and RD13B2. This suggests that scid mutation is responsible for this repair at reduced rate. To confirm the independence of repair of 0.23 M NaCl-sensitive PLD from that of 0.5 M NaCl-sensitive PLD, both treatments with 0.23 M NaCl and 0.5 M NaCl were combined in each line. It is found that the repair of either PLD was not affected by the other treatment. The scid mutation impaired only the repair of 0.5 M NaCl-sensitive PLD.

Two-dimensional free energy surfaces for primary electron transfer in a bacterial photosynthetic reaction center are constructed from the MD simulation results by Warshel et al. [J. Photochem. Photobiol. A: Chem 82 (1994) 123] on the same system by choosing the reaction coordinates appropriately. The activation energies for the direct and sequential electron transfer are calculated using these surfaces. One needs these two-dimensional free energy surfaces to analyze the dynamical solvent effect on the competition between the direct and sequential electron transfer properly, although this effect has so far been analyzed by using one-dimensional free energy curves.

The effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on the recovery from neutropenia induced by fractionated whole-body irradiation was investigated in mice. Male 7-week old C3H/HeN mice received a total of ten exposures of 0.25 Gy/day from day 1 to 5 and from day 8 to 12. Peripheral neutropenia with a nadir on day 17 was caused by the fractionated irradiation. Daily subcutaneous injections of rhG-CSF at 0.25 and 2.5 micrograms/body/day from day 1 to 21 promoted the recovery of neutrophils in a dose-dependent manner. The kinetics of morphologically identifiable bone marrow cells were studied to clarify the mechanism behind the promotive effect of this factor. A slight decrease in mitotic immature granulocytes, such as myeloblasts, promyelocytes and myelocytes on day 5, and a drastic decrease in metamyelocytes and marrow neutrophils on days 5, 9, and 17 were seen in the femur of irradiated mice. Treatment using rhG-CSF caused an increase in immature granulocytes of all differential stages in the femur. Microscopic findings of the femurs and spleens also revealed an increase in immature granulocytes in these organs in mice injected with rhG-CSF. These results indicate that rhG-CSF accelerates granulopoiesis in the femur and spleen, thereby promoting recovery from neutropenia induced by fractionated irradiation.

The dynamical process of a two-step electron transfer (ET) occurring in the supramolecular triad system D-A(1)-A(2) embedded in a polar solvent is theoretically studied. The two-step ET is composed of the initial ET (D*-A(1)-A(2) --> D+-A(1)(-)-A(2)) and following two alternative ETs (forward ET, D+-A(1)(-)-A(2) --> D+-A(1)-A(2)- or backward ET,D+-A(1)-A(2) --> D-A(1)-A(2)). After the solvent free energy functions for the neutral and charged triad systems are expressed in terms of two reaction coordinates which represent the solvent polarization, the branching ratio between the alternative ETs is obtained from the dynamics of the Brownian particle on the free energy surface of the charged state D+-A(1)(-)-A(2) The branching ratio is calculated as a function of the free energy changes of the three ETs, and the values of the free energy changes that maximizes the yield of the forward ET are determined.

The effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on radiation-induced neutropenia and on growth of transplanted tumors treated by irradiation was investigated using tumor-bearing rats as a model for radiation therapy. In a preliminary study using normal rats, neutropenia induced by upper hemi-body irradiation at 3 Gy/day 5 times a week for 3 weeks was prevented by consecutive subcutaneous injections of rhG-CSF at 100 micrograms/kg/day. Rats bearing Walker-256, a mammary tumor, were scheduled to receive upper hemibody irradiation at 3 Gy/day for 15 times in 3 weeks if white blood cell (WBC) counts were maintained above 3,000/microliters. In control tumor-bearing rats not receiving rhG-CSF, irradiation was often withheld because of the decrease in WBC counts below 3,000/microliters. In contrast, a decrease in WBC counts below 3,000/microliters was rarely found in tumor-bearing rats injected daily with rhG-CSF. The average number of radiation treatments in control rats and rats treated with rhG-CSF was about 8 and 14, respectively, out of the scheduled 15 treatments in 3 weeks. Treatment with rhG-CSF made it possible to complete the radiation therapy regimen and thus inhibit the growth of the transplanted tumor more effectively. These results suggest that rhG-CSF may be useful to ensure radiation therapy on schedule in cancer patients.

Proceedings of the 33rd Annual ASTRO Meeting altered mitochondrial membrane potential.After several hours of such deprivation, the mitochondrial membrane potential began to increase.And after 24 hours, the mitochondrial membrane potentials were markedly increased, with resultant increases in accumulation of DLC (JC-1) to 4-10 times baseline level.Up to 6 hours after reoxygenation and return to normal media, there was persistent increased mitochondria uptake of JC-1.Exposure to hypoxia without nutrient deprivations increased the uptake of DLC by 100%.Decreasing the pH of external media to pH 6.2 for 24 hours had no effect on DLC uptake. Conclusion:DLC's were accumulated in much greater levels when cells were exposed to chronic hypoxic and nutrient deprived conditions.Thus, unlike most conventional chemotherapeutic agents, DLC's may be more efficacious in treating hypoxic fractions of solid tumors, and therefore able to work in complement with radiation therapy.

Since most clinical radiotherapy is given as multiple small irradiation fractions, the present study was undertaken to test the in vivo radiosensitizing activity of a new hypoxic cell radiosensitizer, KU-2285, in combination with radiation dose fractionation. Radiosensitizing activity was measured by a growth delay assay using a transplanted mammary tumor in C3H/He mice, and by an in vivo-in vitro assay using the SCC VII tumor. KU-2285 was injected intraperitoneally 30 min before irradiation in all experiments. The in vivo-in vitro assay using SCC VII tumors showed that 12.5 μg/g of KU-2285 sensitized the tumors to irradiation (5 Gy/fr × 5 fr/48 hr or 6 Gy/fr × 3 fr/48 hr). KU-2285 also sensitized the transplanted mammary tumors to fractionated irradiation. We concluded that KU-2285 was able to sensitize two different murine tumors when given in combination with radiation dose fractionation.

1968年8月～1989年12月に60Coγ線を用いて放射線治療を施行した胸腺腫58例, 胸腺癌3例, を対象とし検討した. 放射線治療単独11例, 術前照射1例, 術後照射45例, 術中照射併用4例であった. 胸腺腫についてはa) 術後照射及び術中照射の併用が有効である. b) 術後照射群では, operabilityが予後因子と考えられ, 全摘または亜全摘されたStageIまたはII症例と, 全摘されたStageIII症例が術後照射の適用になりうる. c) 重症筋無力症合併症例は, 非合併症例よりも予後良好であった. 胸腺癌の場合も, 全摘後に充分な線量の術後照射を施行する事によって制御し得る可能性が示唆された.