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Background: Stereotactic body radiotherapy (SBRT) is recognized as a curative treatment for oligometastasis. The spinal cord becomes the cauda equina at the lumbar level, and the nerves are located dorsally. Recently, a consensus has been reached that the cauda equina should be contoured as an organ at risk (OAR). Here, we examined the separate contouring benefits for the spinal canal versus the cauda equina only as the OAR., Materials and Methods: A medical physicist designed a simulation plan for 10 patients with isolated lumbar metastasis. The OAR was set with three contours: the whole spinal canal, cauda equina only, and cauda equina with bilateral nerve roots. The prescribed dose for the planning target volume (PTV) was 30 Gy/3 fx., Results: For the constrained QAR doses, D90 and D95 were statistically significant due to the different OAR contouring. The maximum dose ( D max ) was increased to the spinal canal when the cauda equina max was set to ≤ 20 Gy, but dose hotspots were observed in most cases in the medullary area. The D max and PTV coverage were negatively correlated for the cauda equina and the spinal canal if D max was set to ≤ 20 Gy for both., Conclusions: A portion of the spinal fluid is also included when the spinal canal is set as the OAR. Thus, the PTV coverage rate will be poor if the tumor is in contact with the spinal canal. However, the PTV coverage rate increases if only the cauda equina is set as the OAR., Competing Interests: Conflicts of interest The authors declare that they have no competing interests., (© 2023 Greater Poland Cancer Centre.)

Angiosarcoma of the scalp and face (ASF) is a rare, aggressive tumor often treated with multimodal therapy, including radiation therapy (RT). This study assessed RT outcomes for ASF and identified prognostic factors. Data from 68 non-metastatic ASF patients undergoing RT with or without other therapies were analyzed. Median radiation dose was 66 Gy in 33 fractions (interquartile range (IQR) 60-70 Gy in 28-35 fractions). Local control (LC), progression-free survival (PFS), and overall survival (OS) rates were calculated using Kaplan-Meier analysis. Multivariate analyses and adverse event evaluation were conducted. Median patient age was 75 years (IQR 71-80 years), with a median follow-up of 17 months (IQR 11-42 months). One-/three-year LC rates were 57/37%, PFS rates were 44/22%, and OS rates were 81/44%. Multivariate analyses showed that an equivalent dose in a 2 Gy fraction (EQD 2 ) >66 Gy correlated with improved LC (HR 2.35, 95% CI 1.03-5.32, p = 0.041). Combining chemotherapy (HR 2.43, 95% CI 1.08-5.46, p = 0.032) or surgery (HR 2.41, 95% CI 1.03-5.59, p = 0.041) improved PFS. No factors influenced OS. Late grade 3+ toxicities occurred in 1%, with one patient developing a grade 4 skin ulcer. These findings suggest that EQD 2 > 66 Gy and combining chemotherapy or surgery can enhance LC or PFS in ASF. Further prospective studies are needed to determine the optimal treatment strategy for this rare malignancy, particularly in elderly patients.

To examine the association of clinical, treatment, and dose parameters with late urinary toxicity after low-dose-rate brachytherapy (LDR-BT) for prostate cancer, we retrospectively studied patients with prostate cancer who underwent LDR-BT from January 2007 through December 2016. Urinary toxicity was assessed using the International Prostate Symptom Score (IPSS) and Overactive Bladder (OAB) Symptom Score (OABSS). Severe and moderate lower urinary tract symptoms (LUTS) were defined as IPSS ≥ 20 and ≥ 8, respectively; OAB was defined as a nocturnal frequency of ≥ 2 and a total OABSS of ≥ 3. In total, 203 patients (median age: 66 years) were included, with a mean follow-up of 8.4 years after treatment. The IPSS and OABSS worsened after 3 months of treatment; these scores improved to pretreatment levels after 18-36 months in most patients. Patients with a higher baseline IPSS and OABSS had a higher frequency of moderate and severe LUTS and OAB at 24 and 60 months, respectively. LUTS and OAB at 24 and 60 months were not correlated with the dosimetric factors of LDR-BT. Although the rate of long-term urinary toxicities assessed using IPSS and OABSS was low, the baseline scores were related to long-term function. Refining patient selection may further reduce long-term urinary toxicity.

Introduction: Pretreatment diagnosis by diffusion-weighted magnetic resonance imaging (DW-MRI) is useful to determine the effect of chemotherapy for gastric cancer. Here, we investigated the relationship among DW-MRI, endoscopy, and tumor markers., Patients: Eight patients underwent hemostatic radiotherapy (RT) for gastric cancer in this prospective study from 2019 to 2021. The patients completed MRI, endoscopy, and blood tests before RT; MRI, endoscopy, and blood tests 1 month after RT; and MRI and blood tests 3 months after RT. Correlations between changes in apparent diffusion coefficient (ADC) derived from DW-MRI and the tumor marker carcinoembryonic antigen (CEA) were investigated., Results: Univariate analysis of overall survival showed that sex and chemotherapy treatment were statistically significant factors. The CEA values before and 1 month after RT decreased significantly. There was no statistical difference between the CEA value 1 and 3 months after RT. The ADC value before and 1 month after RT increased significantly but not between 1 and 3 months after RT. Comparing the ratio of ADC before RT to 1 (or 3) month(s) after RT with that of CEA before RT to 1 (or 3) month(s) after RT, we found an inverse relationship between the two ratios., Conclusions: Therefore, changes in ADC and CEA are correlated. Additionally, 3 months after RT, the decrease in ADC appeared earlier than the decrease in CEA. ADC may indicate a biological change earlier than CEA, and the ratios of ADC and CEA may be important factors. These aspects warrant further confirmation in a larger sample population., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aim: This study aimed to examine the usefulness of seed density as a predictor of seed migration in patients with prostate cancer who received brachytherapy using Iodine-125 loose seed., Methods: From May 2006 to April 2016, 320 patients with localized prostate cancer underwent transperineal brachytherapy using iodine-125 loose seeds. Among them, 202 (63.1%) patients received brachytherapy monotherapy and 118 (36.9%) received combined brachytherapy and external beam radiotherapy. Seed density was calculated using the following formula: seed density = implanted seed number/prostate volume. All patients underwent radiography of the chest, abdomen and pelvis, and computed tomography at 1 day, 1 month, and 1 year after brachytherapy to evaluate the presence of seed migration., Results: In total, the number of implanted seeds was 21,876. Seed migration was detected in 92 (28.8%) patients. Of a total of 21,876 seeds, 144 (0.66%) showed migration. The number of needles, number of seeds, and seed density were significantly higher in the group with migration than in the group without migration ( p = 0.05). The ROC cutoff values for prostate volume, number of needles, number of seeds, and seed density were 20.9 cc, 21, 65, and 3.0, respectively. In the univariate analysis, prostate volume, number of needles, number of seeds, seed density, and treatment modality were all significant factors in predicting migration ( p = 0.05). In the multivariate analysis, seed density and treatment modality were significant factors in predicting migration ( p = 0.05)., Conclusion: Seed density is useful for predicting seed migration. In cases with seed density > 3.0, it is necessary to take measures such as considering the use of stranded seeds.

Background: Radiobiological daily changes within tumors are considered to be quite different between stereotactic radiotherapy (SRT) (e.g., 50 Gy in 4 fractions) and conventional radiotherapy (e.g., 60 Gy in 30 fractions). We aim to assess the optimal interval of irradiation in SRT and compare outcomes of daily irradiation with irradiation at two- to three-day intervals in SRT for patients with one to five brain metastases (BM)., Methods: This study is conducted as a multicenter open-label randomized phase II trial. Patients aged 20 or older with one to five BM, less than 3.0 cm diameter, and Karnofsky Performance Status ≥70 are eligible. A total of 70 eligible patients will be enrolled. After stratifying by the number of BMs (1, 2 vs. 3-5) and diameter of the largest tumor (< 2 cm vs. ≥ 2 cm), we randomly assigned patients (1:1) to receive daily irradiation (Arm 1), or irradiation at two- to three-day intervals (Arm 2). Both arms are performed with total dose of 27-30 Gy in 3 fractions. The primary endpoint is an intracranial local control rate, defined as intracranial local control at initially treated sites. We use a randomized phase II screening design with a two-sided α of 0∙20. The phase II trial is positive with p < 0.20. All analyses are intention to treat. This study is registered with the UMIN-clinical trials registry, number UMIN000048728., Discussion: This study will provide an assessment of the impact of SRT interval on local control, survival, and toxicity for patients with 1-5 BM. The trial is ongoing and is recruiting now., Trial Registration: UMIN000048728. Date of registration: August 23, 2022. https://center6.umin.ac.jp/cgi-bin/ctr/ctr&#95;view&#95;reg.cgi?recptno=R000055515 ., (© 2022. The Author(s).)

Background: In clinical practice, the organs at risk (OARs) should be carefully determined when performing pancreatic stereotactic body radiotherapy (SBRT). We conducted a simulation study to examine the effect of the stomach size on the radiation dose to the OARs when performing pancreatic SBRT., Methods: Twenty-five cases were included in this study. Pancreatic head and body tumors were 2-cm-sized pseudotumors, which were included as gross target volume (GTV) contours. The stomach, pancreas, small intestine, liver, kidneys, and spinal cord were considered as the OARs. The prescription dose for planning target volume (PTV) was 40 Gy/5fx, and the dose limit for the OARs was determined. The dose to X% of the OAR volume at X values of 0.1, 5.0, and 10.0 cc (DX) and the percentage of the OAR volume that received more than X Gy were recorded., Results: In terms of the radiation dose to the pancreatic body tumors, the stomach size was positively correlated with a dose of D10cc [correlation coefficient (r) = 0.5516) to the stomach. The r value between the radiation dose to the pancreatic head tumor and the stomach size was 0.3499. The stomach size and radiation dose to the head and body of the pancreas were positively correlated (pancreatic head D10cc: r = 0.3979, pancreatic body D10cc: r = 0.3209). The larger the stomach, the larger the radiation dose to the healthy portion of the pancreas outside the PTV., Conclusions: When performing pancreatic SBRT, the dose to the OARs depends on the stomach size. Reducing the dose to the stomach and pancreas can be achieved by shrinking the stomach., (© 2022. The Author(s).)

Background/aim: Nausea and vomiting are two of the most distressing adverse events of cancer radiotherapy. The aim of this study was to examine the control rate and risk factors associated with nausea and vomiting in patients with cervical cancer receiving radiotherapy., Patients and Methods: This retrospective study examined patients with cervical cancer who received radiotherapy alone or with concomitant cisplatin. Patients who received radiotherapy alone were not administered antiemetic premedication, while patients who received radiotherapy with concomitant weekly cisplatin (40 mg/m 2 ) were administered antiemetic therapy comprising granisetron and dexamethasone. Risk factors for non-complete response (CR) were identified using multivariate logistic regression analysis., Results: Multivariate analysis indicated that younger age and concomitant weekly cisplatin were significant factors associated with non-CR across 5 weeks of treatment in patients who received radiotherapy. The proportion achieving CR among younger patients (<65 years) who received radiotherapy alone or with concomitant cisplatin was significantly lower than that among older patients (≥65 years) (Concomitant cisplatin: 27% vs. 67%, p=0.049; Radiotherapy alone: 62% vs. 91%, p=0.166). However, the proportion of patients achieving CR across 5 weeks of treatment was insufficient in all groups except for those aged ≥ 65 years who received radiotherapy alone., Conclusion: Antiemetic prophylaxis should be considered for younger patients with cervical cancer undergoing radiotherapy alone. Further, neurokinin-1 receptor antagonist should be added to 5-hydroxytryptamine type-3 receptor antagonist and dexamethasone as antiemetic prophylactic therapy for patients with cervical cancer undergoing radiotherapy with concomitant weekly doses of 40 mg/m 2 cisplatin., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objectives: We aimed to compare dual-energy computed tomography (DECT) virtual monochromatic imaging (VMI) and iodine density imaging (IDI) of oral cancers in terms of visual scoring and tumour volume estimation., Materials and Methods: Nine patients diagnosed with oral cancer who underwent DECT VMI and IDI were enrolled. One radiation oncologist, one head and neck surgeon and nine oral surgeons evaluated image clarity and quality in each patient in terms of metal artefacts due to dental prosthesis, internal tumour structure, tumour-organ boundary and total quality of images for diagnosis. Tumour volume was estimated using VMI, IDI and magnetic resonance imaging (MRI)., Results: The mean score for image artefact was significantly higher for IDI than for VMI in three observers, the mean score for internal structure was significantly higher for IDI than for VMI in five, the mean score for tumour-organ boundary was significantly higher for IDI than for VMI in two and the mean score for total quality of images for diagnosis was significantly higher for IDI than for VMI in five. Standard deviation of estimated tumour volume was not significantly different between VMI and IDI, but that of MRI was significantly lowest in three images., Conclusions: In DECT for oral cancer, IDI has a visual image superior to VMI; thus, we recommend the use of IDI., Trial Registration: Clinical trial number: UMIN000038994., (© 2021. Japanese Society for Oral and Maxillofacial Radiology and Springer Nature Singapore Pte Ltd.)

Purpose: There has been an increase in the use of gold fiducial markers to ensure precise radiotherapy delivery in prostate cancer patients. However, metal artifacts may affect the quality of subsequent imaging used to assess disease status following treatment. In this study, we evaluated the effect of gold fiducial markers on magnetic resonance imaging (MRI), particularly on diffusion-weighted imaging (DWI)., Material and Methods: Among 57 patients with prostate cancer, 21 patients in whom two gold markers were placed in the prostate tumor with abnormal signal intensity on DWI were evaluated. The effect of the markers on DWI was evaluated on a scale of 1-5, with a high score indicating clinical usefulness. Change inapparent diffusion coefficient (ADC; 10 -3 mm 2 /s) from before to after marker placement was also evaluated., Results: The mean effect of the markers on DWI was 4.3 (standard deviation [SD] 1.3, range 2-5) points. The mean change in ADC was 0.045 (SD 0.041, range 0.025-0.089) × 10 -3 mm 2 /s., Conclusions: The gold fiducial markers demonstrated negligible effect on DWI quality. Therefore, gold markers do not affect MRI quality, particularly DWI, and may be used during follow-up in prostate cancer patients., (© 2020 John Wiley & Sons Australia, Ltd.)

In this retrospective cohort study, we evaluated the incidence of vascular events from carotid artery atherosclerosis after radiotherapy indication for laryngeal and hypopharyngeal cancer. From January 2007 to December 2016, we investigated 111 laryngeal/hypopharyngeal cancer patients who underwent curative radiotherapy and were followed up for ≥1 year (median follow-up duration, 60 months). We evaluated the incidence of vascular events from carotid artery atherosclerosis, defined as a transient ischemic attack or an atherothrombotic cerebral infarction, or from undergoing treatment such as carotid artery stenting for carotid artery stenosis. The median radiation dose was 66 Gy (range, 60-74); 48 patients (43.2%) received concurrent chemotherapy. The 5-year overall survival was 86.2%. Six patients required treatment for carotid artery disease. Carotid stenting was performed in three patients with carotid artery stenosis; three patients developed atherosclerotic cerebral infarction and received medical treatment, with a median of 51.7 months (range, 0.3-78.3) after radiotherapy initiation. The vascular event occurrence rate was 5.4% within 5 years and 10.7% within 8 years. In the univariate analysis, dyslipidemia, diabetes mellitus, and carotid calcification were significant factors for event occurrence. Because three out of six cases occurred out of the irradiated field, no carotid artery or carotid bulb dosimetric parameters showed significant correlation. As laryngeal/hypopharyngeal cancer patients, particularly with complications including dyslipidemia and diabetes mellitus, are at a high risk of carotid artery stenosis after radiotherapy, long-term carotid artery evaluation is necessary. Early intervention by stroke specialists can reduce the risk of fatal cerebral infarction., Competing Interests: None declared.

Objective: Standard treatment for progressive gastric cancer with bleeding includes hemostatic radiotherapy (RT); however, the only prospective study using a fixed dose with fractions during hemostatic RT did not introduce re-irradiation. Therefore, we determined the utility of RT including re-irradiation for gastric cancer., Methods: In this study, 31 patients with gastric cancer and bleeding were treated with an initial dose of 20 Gy/5 fractions for the whole stomach and a salvage dose of 15 Gy/5 fractions for the partial stomach. Patients achieving hemostasis, defined as a stable hemoglobin level within 30 days following irradiation, were considered responders, whereas those with no cessation of bleeding and those with re-bleeding within 30 days of irradiation were considered non-responders. We evaluated response rate, disease-free survival, overall survival (OS), re-irradiation, and adverse events (AEs)., Results: The response rate of initial RT was 80% (25/31). 6 of the 25 patients underwent re-irradiation, and all 6 were responders (100%). The median OS was significantly different among the entire cohort and one-time irradiation and re-irradiation groups (91, 76, and 112 days, respectively). No AEs of grade ≥3 were observed. Initial low-dose RT followed by reirradiation was effective in reducing AEs and did not cause any further AEs., Conclusion: Hemostatic RT was an effective approach with low toxicity, and re-irradiation was effective and tolerable, with no patients developing severe AEs. Further, randomized controlled studies are warranted to determine the ideal dose and number of fractions for initial RT in patients with gastric cancer and bleeding., Advances in Knowledge: In this prospective study on hemostatic radiotherapy for gastric cancer, the response rate was 80% using a fixed dose of 20 Gy/5 fractions and the salvage dose of 15 Gy for re-bleeding was effective. Future comparative studies should include other doses with 20 Gy as a control.

Bone-modifying agents (BMAs) are frequently used for the treatment of bone metastases. Both BMA and radiation therapy (RT) are effective; however, there are few studies that have evaluated the efficacy of the combination treatment. We evaluated the effectiveness of RT + BMA in breast cancer-induced osteolytic bone metastasis as compared to BMA alone. A total of 43 lesions in 25 patients were evaluated. The median follow-up period was 18 (range, 2-90) months. None of the lesions was treated with chemotherapy or molecular targeted drugs during the follow-up period for evaluating the local response. Patients with complete or partial response were considered as responders, while those with stable or progressive disease were considered as non-responders. The rate of response with RT + BMA was significantly higher than that with BMA alone (P = 0.001). The cumulative incidence rate of response at 6 months was 54.4% in the RT + BMA group and 27.5% in the BMA alone group. The median time to response was 4 (range, 2-11) months in the RT + BMA group and 6 (range, 4-16) months in the BMA alone group. The overall survival rate in the responder group (83.1% at 1 year) was significantly higher than that in the non-responder group (37.5% at 1 year) (P = 0.029). In conclusion, RT combined with BMA was found to be more effective than BMA alone for the treatment of osteolytic bone metastasis, which thereby improves the prognosis., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Stereotactic body radiotherapy (SBRT) delivers high-dose radiation to tumor tissues in few fractions, thereby reducing radiation damage to at-risk organs. There are more potential effects of SBRT owing to the higher biological equivalent dose delivered. Herein, we retrospectively analyzed its effectiveness and toxicity at our institution., Methods: Data from patients with hepatocellular carcinoma (HCC; n = 10) and liver metastases (n = 10) who underwent SBRT (total dose of 30-50 Gy in 5-10 fractions) between 2013 and 2016 were analyzed. Adverse events were recorded at the end of RT, 6 months after treatment, or upon death. Overall survival (OS) was calculated according to the biological effective dose (BED α/β = 10) and liver function (Child-Pugh [CP] classification 5 or 6 vs. 7 or 8) after SBRT, using Kaplan-Meier analyses., Results: Of the 20 patients, 6 declined the CP classification score after SBRT; grade 3 adverse events were not seen in any patient. A higher OS rate was seen in patients receiving a higher BED and in those with better CP classification after SBRT. Kaplan-Meier survival analysis yielded a median OS of 401 days and 1- and 2-year OS of 45% and 15%, respectively., Conclusion: The higher BED was significantly associated with tumor control, and there were no differences in the tumor control rate between HCC and metastatic tumors. Changes in CP scores after SBRT also affected the survival rate. Good liver function may permit multiple rounds of SBRT., (© 2019 Indian National Association for Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Intensity-modulated radiotherapy (IMRT) has been used for breast cancer as well as in field-in-field techniques. Few dosimetric comparison studies have been conducted using IMRT and volumetric modulated arc therapy (VMAT) for Japanese patients. We aimed to study such patients. Thirty-two patients with left-sided breast cancer were enrolled. We conducted the following five treatment plans: two field-static IMRT (2F-S-IMRT), four field-static IMRT (4F-S-IMRT), 40° dual partial arc VMAT (40d-VMAT), 80° dual partial arc VMAT (80d-VMAT) and 210° partial VMAT (210p-VMAT). We evaluated the following: level of coverage of planning target volume (PTV) of 95% for irradiation at a dose of 50 Gy (D95) and the percentage of the heart and left anterior descending artery (LAD) volume that received 10 Gy or more (V10). As a result, the coverage of 40d-VMAT for the prescribed PTV dose of D95 was significantly lower than that of the other treatment plans (P < 0.05). Regarding heart V10 and LAD V10, 2F-S-IMRT, 40d-VMAT and 80d-VMAT showed significantly lower dose than the other treatment plans (P < 0.05). In conclusion, among the five plans, 2F-S-IMRT is recommended for Japanese patients because of high coverage of D95 of PTV, low V10 of the heart and LAD and the monitor unit value was the lowest., (© The Author(s) 2019. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

The present study aimed to clarify the incidence and clinical outcomes of nasopharyngeal carcinoma (NPC) in the Chubu region of Japan from 2006 to 2015, compared with previous reports. A retrospective analysis was conducted based on medical records from 40 hospitals located in the Chubu region in the central Japanese main island, with a population of around 22.66 million individuals. This study was designed in line with to two previous clinical studies into NPC conducted in the same area of Japan. We recruited NPC patients diagnosed in hospitals across this area over a 10-year period (2006-2015) using a questionnaire about sex, age, primary site, clinical symptoms, pathology, Union for International Cancer Control (UICC) staging, serological exam, treatment, and survival. A total of 620 NPC patients were identified. The age-standardized incidence of NPC from 2006 to 2015 was 0.27 per 100,000 individuals per year. There were no significant differences between this study and the previous two studies conducted in the same area of Japan. The five-year overall survival rate for all patients was 75.9%, while those for patients with stages I, II, III, and IVA were 97%, 91%, 79%, and 68%, respectively. The age-standardized annual incidence of NPC in the present study was 0.27 per 100,000 individuals per year, which was relatively low and stable. The five-year overall survival rate for all NPC patients was significantly improved in this decade compared with previous studies. The smoking rates in male and female NPC patients were 64.5% and 18.8%, respectively, thereby suggesting the involvement of smoking in the incidence of NPC.

Helical tomotherapy (HT) can restrict beamlets passing through the virtual contour on computed tomography (CT) image in dose optimization, reducing the dose to organs at risk (OARs). Beamlet restriction limits the incident beamlet angles; thus, the proper planning target volume (PTV) margin may differ from that of the standard treatment plan without beamlet restriction, depending on the patient's movement during dose delivery. Dose distribution changes resulting from patient movement have not been described for treatment plans with beamlet restriction. This study quantified changes in dose distribution to the target and OARs when beamlet restriction is applied to cervical esophageal cancer treatment plan using HT by systematically shifting a phantom. Treatment plans for cervical esophageal cancers with and without beamlet restriction modes [directional block (DB) and nonblock (NB), respectively] were designed for CT images of the RANDO phantom. The PTV margin for the DB mode was set to be the same as that for the NB mode (5 mm). The CT image was intentionally shifted by ±1, ±2, and ±3 voxels in the left-right, anterior-posterior, and superior-inferior directions, and the dose distribution was recalculated for each position using the fluence for the NB or DB mode. When the phantom shift was within the same PTV margin as the NB mode, changes in doses to the targets, lungs, heart, and spinal cord in the DB mode were small as those in the NB mode. In conclusion, the virtual contour shape used in this study would provide safe delivery even with patient movement within the same PTV margin as for the NB mode., (© 2019 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

Objective: The aim of this study was to compare the outcomes and toxicities of radical hysterectomy (RH) and definitive chemoradiation (CRT) for International Federation of Gynecology and Obstetrics (FIGO) stage IIB cervical cancer., Materials and Methods: A retrospective analysis was performed on FIGO stage IIB patients who underwent RH with adjuvant radiotherapy (surgery group) or intended to receive CRT (CRT group). The distributions of disease-free survival (DFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Propensity score matching (PSM) was performed for the 2 groups based on age, tumor diameter, histological type, and pelvic node metastasis in pretreatment imaging tests., Results: Median follow-up times were 58 months in the surgery group (n = 75) and 55 months in the CRT group (n = 65). Propensity score matching identified 37 patients with similar characteristics from each group. Significant differences were observed in the ratio of the chemotherapy combination between the surgery and CRT groups before (47% vs 98%) and after PSM (51% vs 100%). Five-year DFS rates were slightly higher in the surgery group than in the CRT group before PSM (69% vs 58%, P = 0.30) but were similar after PSM (76% vs 82%, P = 0.36). Five-year OS rates were similar between the surgery and CRT groups before (70% vs 75%, P = 0.59) and after PSM (78% vs 77%, P = 0.97). The results of multivariate analyses also showed that neither DFS nor OS was associated with the treatment modalities regardless of PSM. The incidence of late toxicities grade 2 or greater was similar between the surgery and CRT groups before (17% vs 23%, P = 0.31) and after PSM (19% vs 24%, P = 0.78)., Conclusions: The results of this study suggest that RH with adjuvant radiotherapy and definitive CRT are equivalent treatment options for patients with FIGO stage IIB cancer. However, prospective larger studies are needed to confirm this.

Introduction: Pterygium surgery is marked by the possibility of recurrences; one of the techniques which results in the least recurrences is conjunctival autograft. Fixation of the conjunctiva had traditionally been accomplished with sutures. In recent years, conjunctival grafting has also been performed with fibrin glue. Even more recently, with a view towards improving the quality of postoperative results, some surgeons recommend the use of autologous blood. This study aims to evaluate the stability of this latest method of graft fixation, while assessing its postoperative results., Methodology: After diagnosis of pterygium, the patients underwent pterygium surgery with a conjunctival graft fixated with autologous blood. They were then monitored for one year, at 24h postoperatively, then seven days, 15 days, one month 3months, and every 3months thereafter., Results: In totl, 84.21 % of the patients demonstrated stable postoperative fixation; 5.26 % of patients experienced significant displacement of the graft. After one year of follow-up, 15.79 % of patients experienced recurrent pterygium. Recurrences were more frequent in younger patients and in patients with previous recurrence., Conclusion: Pterygium surgery by conjunctival graft fixated with autologous blood is a safe surgery, with results similar to other pterygium surgery techniques with conjunctival autograft. However, this technique has the advantage less irritation, no risk of transmitting infection and lower cost., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Background: Intensity-modulated radiotherapy is useful for cervical oesophageal carcinoma (CEC); however, increasing low-dose exposure to the lung may lead to radiation pneumonitis. Nevertheless, an irradiation technique that avoids the lungs has never been examined due to the high difficulty of dose optimization. In this study, we examined the efficacy of helical tomotherapy that can restrict beamlets passing virtual blocks during dose optimization computing (block plan) in reducing the lung dose., Methods: Fifteen patients with CEC were analysed. The primary/nodal lesion and prophylactic nodal region with adequate margins were defined as the planning target volume (PTV)-60 Gy and PTV-48 Gy, respectively. Nineteen plans per patient were made and compared (total: 285 plans), including non-block and block plans with several shapes and sizes., Results: The most appropriate block model was semi-circular, 8 cm outside of the tracheal bifurcation, with a significantly lower lung dose compared to that of non-block plans; the mean lung volumes receiving 5 Gy, 10 Gy, 20 Gy, and the mean lung dose were 31.3% vs. 48.0% (p <  0.001), 22.4% vs. 39.4% (p <  0.001), 13.2% vs. 16.0% (p = 0.028), and 7.1 Gy vs. 9.6 Gy (p <  0.001), respectively. Both the block and non-block plans were comparable in terms of the homogeneity and conformity indexes of PTV-60 Gy: 0.05 vs. 0.04 (p = 0.100) and 0.82 vs. 0.85 (p = 0.616), respectively. The maximum dose of the spinal cord planning risk volume increased slightly (49.4 Gy vs. 47.9 Gy, p = 0.002). There was no significant difference in the mean doses to the heart and the thyroid gland. Prolongation of the delivery time was less than 1 min (5.6 min vs. 4.9 min, p = 0.010)., Conclusions: The block plan for CEC could significantly reduce the lung dose, with acceptable increment in the spinal dose and a slightly prolonged delivery time.

Objective: We aimed to examine the effects of a dose escalation for prostate cancer patients receiving long-term androgen deprivation therapy (ADT)., Methods: A retrospective analysis of 605 patients treated with radiotherapy (RT) and long-term ADT (National Comprehensive Cancer Network criteria-defined intermediate-risk, minimum 10 months; high-risk and very-high-risk, minimum 20 months) was performed. The median ADT time was 31 months. Cox's proportional hazards models were used to compare biochemical disease-free survival (bDFS), clinical relapse-free survival (cRFS) and overall survival (OS) between the ≥70, <78 Gy group and 78 Gy group in a univariate analysis and to assess the effects of the dose escalation on bDFS in a multivariate analysis., Results: After a median follow-up of 70 months, 5-year bDFS was significantly better in the 78 Gy group than in the ≥70, <78 Gy group [96 vs 83%; hazard ratio 3.6 (95% confidence interval 2.2-6.1); p < 0.001]. 5-year cRFS and OS were similar between the two groups. The multivariate analysis showed that RT dose was still an independent prognostic factor of bDFS (p = 0.005)., Conclusion: The results of the present study suggest that dose escalations result in significant improvements in bDFS, even when used in combination with long-term ADT. A longer follow-up is needed to clarify the effects of dose escalations on cRFS and OS. Advances in knowledge: It remains unclear whether high-dose RT is necessary for improving the outcomes of patients receiving long-term ADT. The results suggest that dose escalations result in significant improvements in biochemical control.

Purpose: We previously reported unfavorable locoregional control with limited field postoperative radiotherapy for head and neck squamous cell carcinoma patients and thus revised the strategy to cover the whole neck. Head and neck squamous cell carcinoma Patients' outcomes were retrospectively analyzed to compare the efficacy of two treatments., Material and Methods: Before 2010, the clinical target volume covered the tumor bed and/or involved the neck region. Since 2011, whole-neck irradiation was planned. Univariate analysis, multivariate analysis, and propensity score matching were performed. The study included 275 patients: 186 received limited field postoperative radiotherapy and 89 received whole-neck postoperative radiotherapy. The median follow-up time for the entire cohort was 40.8 months., Results: In univariate analysis, the radiation strategy had no significant effect on overall survival and progression-free survival. In multivariate analysis, whole-neck postoperative radiotherapy was a favorable factor for overall survival, progression-free survival, and locoregional control. Propensity score matching resulted in a cohort comprising 118 well-matched patients evenly divided between the limited field postoperative radiotherapy and whole-neck postoperative radiotherapy groups. Whole-neck postoperative radiotherapy group achieved a significantly better 2-year overall survival (56.4% vs. 78.1%; P = 0.003), 2-year progression-free survival (34.7% vs. 59.8%; P = 0.009), and 2-year locoregional control (54.4% vs. 83.2%; P < 0.001). The limited field postoperative radiotherapy group developed significantly more locoregional recurrences both in-field (35.2% vs. 15.1%, P = 0.003) and out-of-field (25.0% vs. 0%, P < 0.001) in the matched-pair cohort., Conclusion: Whole-neck postoperative radiotherapy is a more appropriate choice than limited field postoperative radiotherapy to improve overall survival, progression-free survival and locoregional control., (© The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com)

Background: The efficacy of intensity-modulated radiotherapy (IMRT) for cervical esophageal cancer has not been determined., Methods: Eighty patients with cervical esophageal cancer treated with definitive chemoradiotherapy from 2002 to 2014 were analyzed. Overall survival (OS), failure patterns, and toxicity incidence were compared between the IMRT (N = 32) and 3D conformal radiotherapy (RT; N = 48) groups., Results: The median follow-up was 35.9 months. The 3-year OS of the IMRT, 3D conformal RT, and total groups was 81.6%, 57.2%, and 66.6%, respectively. Pulmonary toxicity was not observed with IMRT. Six of 62 cases (9.6%) with nodal involvement developed upper cervical node recurrence outside the prophylactic region. Ten patients in the IMRT group were salvaged, and 60% survived without recurrence; 20% of the 3D conformal RT group was salvaged., Conclusion: The IMRT group was comparable with 3D conformal RT group, with a better salvage rate. We recommend extended cervical irradiation for nodal involvement., (© 2017 Wiley Periodicals, Inc.)

A low modulation factor (MF) maintaining a good dose distribution contributes to the shortening of the delivery time and efficiency of the treatment plan in helical tomotherapy. The purpose of this study was to reduce the delivery time using initial values and the upper limit values of MF. First, patients with head and neck cancer (293 cases) or prostate cancer (181 cases) treated between June 2011 and July 2015 were included in the analysis of MF values. The initial MF value (MF initial ) was defined as the average MF actual value, and the upper limit of the MF value (MF UL ) was defined according the following equation: MF UL = 2 × standard deviation of MF actual value + the average MF actual Next, a treatment plan was designed for patients with head and neck cancer (62 cases) and prostate cancer (13 cases) treated between December 2015 and June 2016. The average MF actual value for the nasopharynx, oropharynx, hypopharynx, and prostate cases decreased from 2.1 to 1.9 (p = 0.0006), 1.9 to 1.6 (p < 0.0001), 2.0 to 1.7 (p < 0.0001), and 1.8 to 1.6 (p = 0.0004) by adapting the MF initial and the MF UL values, respectively. The average delivery time for the nasopharynx, oropharynx, hypopharynx, and prostate cases also decreased from 19.9 s cm -1 to 16.7 s cm -1 (p < 0.0001), 15.0 s cm -1 to 13.9 s cm -1 (p = 0.025), 15.1 s cm -1 to 13.8 s cm -1 (p = 0.015), and 23.6 s cm -1 to 16.9 s cm -1 (p = 0.008) respectively. The delivery time was shortened by the adaptation of MF initial and MF UL values with a reduction in the average MF actual for head and neck cancer and prostate cancer cases., (© 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

Objective: To analyze the clinical outcome of concurrent chemoradiotherapy in superficial esophageal cancer patients., Methods: We retrospectively analyzed data for 123 patients with superficial esophageal cancer who received external beam radiotherapy without intracavitary brachytherapy plus systemic chemotherapy during 1998-2015. Elective nodal irradiation was not performed. The dosage to planning treatment volume was 60 Gy in 30 fractions. The main outcome measure was overall survival., Results: Patient characteristics were as follows: median age, 66 (41-83) years; male/female ratio, 106/17; squamous cell carcinoma/other, 122/1; cT1a/cT1b, 27/96; cervical esophagus/upper thoracic esophagus/middle thoracic esophagus/lower thoracic esophagus, 7/9/66/41 and concurrent chemoradiotherapy/radiotherapy alone, 100/23. Cisplatin and 5-fluorouracil were the most commonly used agents (85%). At the last follow-up (median 60.5 months), 91 (74%) patients were alive. Complete response was achieved in 116 (94.4%) patients. The 5-year overall survival, progression-free survival and local control rates were 77.0, 46.9 and 62.7%, respectively, similar to that in the elderly patients (P = 0.878, 0.754 and 0.648, respectively). There were 55 failures: 42 local, 10 regional and 3 distant failures. Nine local and seven regional failures developed out-of-field. Thirty-eight local failures (90%) were successfully salvaged, of which 30 (71%) were salvaged via endoscopic removal; only 2 regional failures (20%) were salvaged. Fifteen G3 acute toxicities occurred. One pneumonitis (G3), one pneumothorax (G3) and two pericardial effusion (G2) were the late toxicities observed. There were no G4 toxicities or treatment-related deaths., Conclusions: Concurrent chemoradiotherapy without intracavitary brachytherapy was effective and safe for superficial esophageal cancer, even in elderly patients., (© The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com)

Purpose: We decided to evaluate the decrease in intraocular pressure six months after cataract surgery., Materials and Methods: We evaluated patients' IOP using an applanation tonometer. The patients then underwent cataract surgery. Six months after cataract surgery, we reevaluated the IOP by the same method, and we determined the post-operative change., Results: Among the 147 operated eyes, 123 eyes or 83.67% exhibited a decrease in IOP. The mean preoperative IOP for the operative eye was 15.61±4.5mmHg; the mean post-operative IOP was 12.57±3.5mmHg; the mean IOP decrease after surgery was 3.16±4mmHg, for a mean decrease of 20%. This decrease is statistically significant, P<001. The decrease in IOP varies proportionally to the initial IOP. In glaucomatous patients, the mean preoperative IOP was 23.16±5.68mmHg and mean post-operative IOP was 14.5±2.7mmHg, a decrease of 37.39%., Conclusion: The decrease in IOP after cataract surgery was generally moderate. However, this IOP decreased proportionally to the initial IOP, thus giving significant decreases for higher IOPs. This decrease in IOP, well known after phacoemulsification, was also obtained after Manual Small Incision Cataract Surgery, a surgical technique which is increasingly employed in developing countries., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Purpose: We aimed to examine outcomes of high-dose radiotherapy with helical tomotherapy (HT) and long-term androgen deprivation therapy (ADT) for T1-4N0M0 prostate cancer., Methods: A total of 391 patients treated with HT between June 2006 and December 2013 were included in this retrospective study. All patients received neoadjuvant ADT for a median duration of 10 months followed by HT at a median dose of 78 Gy [interquartile range (IQR) 78-78]. The times of median adjuvant and total ADT were 19 and 27 months (IQR 20-31), respectively. The risk stratification followed the 2015 National Comprehensive Cancer Network criteria. Biochemical disease-free survival (bDFS) followed the Phoenix definition. Toxicity was scored according to the Radiation Therapy Oncology Group morbidity grading scale., Results: Median follow-up from HT start was 60 months (IQR 42-81). Five-year bDFS rates for low-, intermediate-, high-, and very-high-risk groups were 100, 98.2, 97.7, and 87.9 %, respectively. We observed clinical relapse in nine very-high-risk patients and one high-risk patient, resulting in a 5-year clinical relapse-free survival of 100, 100, 99.4, and 91.7 %, respectively, for each risk group. Three patients died of prostate cancer, resulting in a 5-year prostate cancer-specific survival of 99.6 %. The late grade 2 or higher gastrointestinal and genitourinary toxicities were 9.7 and 10.7 %. No cardiovascular fatal events were observed., Conclusions: This report confirmed the excellent outcomes with acceptable late toxicities with the combination of HT and long-term ADT. Longer follow-up is crucial to further determine the treatment effect and toxicity.

Objective: High Charlson comorbidity index values have been reported to be associated with shorter overall survival in various types of cancer. We investigated whether Charlson comorbidity index values were correlated with overall survival in patients with resectable sinonasal tract squamous cell carcinoma., Methods: Seventy-nine patients with resectable sinonasal tract squamous cell carcinoma were treated with curative intent. The Charlson comorbidity index values were calculated by the summation of the weight scores of 19 medical conditions (other than sinonasal tract squamous cell carcinoma) before treatment. The survival rate was analyzed according to the Kaplan-Meier method. Univariate and multivariate survival analyses were performed using the Wilcoxon test and the Cox proportional hazards model, respectively., Results: According to a univariate analysis, a Charlson comorbidity index value ≥6 was found to be significantly correlated with shorter overall survival (P < 0.02). In the multivariate survival analysis with adjustment for the clinical T and N classification, age, sex, anatomical location, treatment group (radiotherapy/surgery) and chemotherapy (presence/absence), a Charlson comorbidity index value ≥6 was found to be associated with the significantly shorter overall survival., Conclusions: These results suggest that the Charlson comorbidity index functions as a prognostic factor in cases of resectable sinonasal tract squamous cell carcinoma., (© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: A retrospective analysis was performed to evaluate the clinical efficacy of definitive chemoradiotherapy including intensity-modulated radiotherapy for patients with hypopharyngeal cancer., Methods: Previously untreated 204 patients with hypopharyngeal cancer were treated with definitive chemoradiotherapy. Of note, 66-70 Gy was delivered to the primary and involved nodes and 36-54 Gy was delivered to the prophylactic lymph node using standard fractionated radiotherapy. One hundred and forty-six patients received induction chemotherapy as a larynx preservation strategy, followed by definitive radiotherapy with or without concurrent chemotherapy. Intensity-modulated radiotherapy was also performed after 2006., Results: The median follow-up time of this cohort was 43.4 months (range; 6.9-151.0). The 3-year overall survival, progression-free survival and larynx preservation survival rates were 78.8% (95% confidence interval; 73.0-85.0), 58.4% (95% confidence interval; 51.8-65.9) and 67.5% (95% confidence interval; 61.0-74.7), respectively. Multivariate analyses identified the following significant prognostic factors: an advanced age, the T category and N category for overall survival, the T category and N category for progression-free survival and the T category for larynx preservation survival. Acute toxicities of Grade 3 or higher were observed in 47 patients (23.0%). Two patients (1.0%) had Grade 4 pharyngeal edema. Suspicious treatment-related death due to lethal pharyngeal hemorrhage occurred in 1 (0.4%) patient. The rates of Grade 2 xerostomia in patients treated with intensity-modulated radiotherapy were 28.1, 17.4 and 9.5% at 6 months, 1 and 2 years after the completion of radiotherapy, respectively., Conclusions: The efficacy and safety of definitive chemoradiotherapy are considered feasible with sufficient laryngeal preservation., (© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Purpose: Proton beam therapy (PBT), compared with conventional radiotherapy, can deliver high-dose radiation to a tumor, while minimizing doses delivered to surrounding normal tissues. The better dose distribution of PBT may contribute to the improvement in local control rate and reduction in late adverse events. We evaluated therapeutic results and toxicities of PBT combined with selective intra-arterial infusion chemotherapy (PBT-IACT) in patients with stage III-IVB squamous cell carcinoma of the tongue., Materials and Methods: After 2 systemic chemotherapy courses and whole-neck irradiation (36 Gy in 20 fractions), we administered concurrent chemoradiotherapy comprising PBT for the primary tumor [28.6-33 Gy(RBE) in 13-15 fractions] and for the metastatic neck lymph node [33-39.6 Gy(RBE) in 15-18 fractions] with weekly retrograde intra-arterial chemotherapy by continuous infusion of cisplatin with sodium thiosulfate., Results: Between February 2009 and September 2012, 33 patients were enrolled. The median follow-up duration was 43 months. The 3-year overall survival, progression-free survival, local control rate, and regional control rate for the neck were 87.0, 74.1, 86.6, and 83.9 %, respectively. Major acute toxicities >grade 3 included mucositis in 26 cases (79 %), neutropenia in 17 cases (51 %), and dermatitis in 11 cases (33 %). Late grade 2 osteoradionecrosis was observed in 1 case (3 %)., Conclusions: PBT-IACT for stage III-IVB tongue cancer has an acceptable toxicity profile and showed good treatment results. This protocol should be considered as a treatment option for locally advanced tongue cancer.

The effect of proton beam therapy (PBT) on various cancers is controversial. We aimed to evaluate the efficacy and safety of PBT with alternating chemoradiotherapy (ACRT) for patients with stage I-III esophageal cancer. Two cycles of systemic chemotherapy with a continuous infusion of 5-fluorouracil (5-FU) on days 1-5 and a 5h infusion of nedaplatin (NDP) on day 6 were accompanied by thoracic irradiation using X-ray therapy and PBT. During the first half of the treatment, X-rays were delivered to the prophylactic area. During the second half of the treatment, proton beams were used to irradiate the involved field. To reduce the dose of cardiac irradiation, proton beams were delivered with posterior and posterior oblique angles. Between January 2009 and December 2012, 47 patients were enrolled in this study. The median follow-up duration was 29 months for all patients and 40 months for survivors. The 3 year overall survival rate, progression-free survival rate, and local control rate were 59.2%, 56.3%, and 69.8%, respectively. With respect to grade 3-4 late toxicities, there were no pleural or pericardial effusions, but two patients (4.3%) had esophageal stenosis, one patient (2.1%) had fistula, and two patients (4.3%) developed radiation pneumonitis. PBT with ACRT might have the potential to reduce the risk of cardiac damage and might become one of the primary methods of esophageal cancer treatment., (© 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Objective: To evaluate the clinical outcomes of intensity-modulated radiotherapy for patients with oropharyngeal carcinoma., Methods: Ninety-three oropharyngeal carcinoma patients histopathologically diagnosed with squamous cell carcinoma and treated with definitive intensity-modulated radiotherapy using helical tomotherapy between January 2006 and December 2013 were analyzed. Planning target volume primary and involved nodes was delivered 66-70 Gy at 2 Gy per fraction, while planning target volume prophylactic was delivered 54 Gy using the simultaneous integrated boost technique., Results: The median follow-up period among the surviving patients was 40 months (range, 13-96). There were 76 males and 17 females with a median age of 60 years (range, 34-80). The disease was Stage II in 13%, Stage III in 10% and Stage IV in 77% of patients. Ninety-two patients received chemotherapy (99%); 68 patients received induction chemotherapy (73%), while 21 received concurrent chemotherapy (23%). The 3-year overall survival, progression-free survival and locoregional control rates were 80, 68 and 79%, respectively. Multivariate analysis identified an advanced T-category (T3-4), having double cancer, and smoking habit as significantly unfavorable factors for overall survival, progression-free survival and both progression-free survival and locoregional control, respectively. Only two patients who achieved disease control required percutaneous endoscopic gastrostomy tubes in the last follow-up. The rate of Grade 2 xerostomia at 2 years was 23%., Conclusions: Intensity-modulated radiotherapy using helical tomotherapy for patients with oropharyngeal carcinoma provided not only sufficient efficacy, but also preserved parotid function., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

The purposes of this study on prostate cancer are to demonstrate the time course of International Prostate Symptom Score (IPSS) after intensity-modulated radiation therapy (IMRT) combined with androgen deprivation therapy (ADT) and to examine the factor associated with the IPSS change. This study included 216 patients treated with IMRT between 2006 and 2010. Patients were evaluated in three groups according to baseline IPSS as defined by the American Urological Association classification, where IPSSs of 0 to 7, 8 to 19, and 20 to 35 represent mild (n = 124), moderate (n = 70), and severe (n = 22) symptom groups, respectively. The average IPSSs ± standard deviation at baseline vs. those at 24 months after IMRT were 3.5 ± 2.1 vs. 5.1 ± 3.6 in the mild group (P < 0.001), 12.6 ± 3.4 vs. 10.0 ± 6.0 in the moderate group (P = 0.0015), and 23.8 ± 2.9 vs. 14.4 ± 9.1 in the severe group (P < 0.001). Among factors of patient and treatment characteristics, age, IPSS classification, pretreatment GU medications, and positive biopsy rates were associated with the IPSS difference between baseline and 24 months (P = 0.023, < 0.001, 0.044, and 0.028, respectively). In conclusion, patients with moderate to severe urinary symptoms can exhibit improvement in urinary function after IMRT, whereas patients with mild symptoms may have slightly worsened functions. Age, baseline IPSS, GU medications, and tumor burden in the prostate can have an effect on the IPSS changes.

In stereotactic body radiotherapy (SBRT) for centrally located non-small cell lung carcinoma (NSCLC), severe hemoptysis has been reported in several studies. We report here a rare case of hemoptysis after SBRT even though the lung tumor was peripherally located. A lung nodule of a 79-year-old man was accidentally found at the periphery of the left upper lobe. A computed tomography-guided biopsy of this nodule provided confirmation of the diagnosis of poorly differentiated adenocarcinoma. The clinical diagnosis was T1bN0M0, stage I primary lung cancer. The patient was treated with SBRT using helical tomotherapy at a dose of 60 Gy in 6 fractions (i.e., BED10 = 120). He obtained a complete response and did not experience recurrence. However, the patient suffered massive hemoptysis 4.5 years after SBRT. As hypervascularity of a left bronchial artery was observed at the left lung in accordance with SBRT field on bronchial arteriography, a bronchial artery embolization (BAE) procedure was performed. The patient has had no episodes of hemoptysis after BAE. Although SBRT for early stage NSCLC is usually safe and efficient, it is necessary to be careful for late-onset bronchial hemorrhage in SBRT, even for a peripheral tumor.

Background: Evidence has suggested that radiation therapy with a lower dose per fraction may be a reasonable option for the treatment of centrally located non-small cell lung cancer (NSCLC). The aim of this study was to evaluate the safety and efficacy of two proton beam therapy (PBT) protocols for stage I NSCLC and to determine prognostic factors., Material and Methods: This study included patients clinically diagnosed with stage I NSCLC. Based on the location of the tumor, one of the two PBT protocols was administered. Patients with peripherally located tumors were given 66 Gy relative biological dose effectiveness (RBE) over 10 fractions (Protocol A) while patients with centrally located tumors were given 80 Gy (RBE) over 25 fractions (Protocol B)., Results: Between January 2009 and May 2012, 56 eligible patients were enrolled (protocol A: 32 patients; protocol B: 24 patients). The three-year overall survival (OS), progression-free survival (PFS), and local control (LC) rates were 81.3% [95% confidence interval (CI) 75.9-86.7%], 73.4% (95% CI 67.2-79.6%), and 96.0% (95% CI 93.2-98.8%), respectively. There were no significant differences in outcomes between the two protocols. Late grade 2 and 3 pulmonary toxicities were observed in nine patients (13.4%) and one patient (1.5%), respectively; no grade 4 or 5 toxicities were observed. Sex, age, performance status, T-stage, operability, and tumor pathology were not associated with OS and PFS. Only maximum standardized uptake value (SUVmax; <5 vs. ≥5) was identified as a significant prognostic factor for OS and PFS., Conclusion: Both high-dose PBT protocols achieved high LC rates with tolerable toxicities in stage I NSCLC patients, and SUVmax was a significant prognostic factor.

Background: We examined the efficacy and toxicity of proton beam therapy (PBT) for treating advanced cholangiocarcinoma., Methods: The clinical data and outcomes of 28 cholangiocarcinoma patients treated with PBT between January 2009 and August 2011 were retrospectively examined. The Kaplan-Meier method was used to estimate overall survival (OS), progression-free survival (PFS), and local control (LC) rates, and the log-rank test to analyze the effects of different clinical and treatment variables on survival. Acute and late toxicities were assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0., Results: The median age of the 17 male and 11 female patients was 71 years (range, 41 to 84 years; intrahepatic/peripheral cholangiocarcinoma, n = 6; hilar cholangiocarcinoma/Klatskin tumor, n = 6; distal extrahepatic cholangiocarcinoma, n = 3; gallbladder cancer, n = 3; local or lymph node recurrence, n = 10; size, 20-175 mm; median 52 mm). The median radiation dose was 68.2 Gy (relative biological effectiveness [RBE]) (range, 50.6 to 80 Gy (RBE)), with delivery of fractions of 2.0 to 3.2 Gy (RBE) daily. The median follow-up duration was 12 months (range, 3 to 29 months). Fifteen patients underwent chemotherapy and 8 patients, palliative biliary stent placement prior to PBT. OS, PFS, and LC rates at 1 year were 49.0%, 29.5%, and 67.7%, respectively. LC was achieved in 6 patients, and was better in patients administered a biologically equivalent dose of 10 (BED10) > 70 Gy compared to those administered < 70 Gy (83.1% vs. 22.2%, respectively, at 1 year). The variables of tumor size and performance status were associated with survival. Late gastrointestinal toxicities grade 2 or greater were observed in 7 patients <12 months after PBT. Cholangitis was observed in 11 patients and 3 patients required stent replacement., Conclusions: Relatively high LC rates after PBT for advanced cholangiocarcinoma can be achieved by delivery of a BED10 > 70 Gy. Gastrointestinal toxicities, especially those of the duodenum, are dose-limiting toxicities associated with PBT, and early metastatic progression remains a treatment obstacle.

Background: We planned a phase I study of weekly arterial infusion of docetaxel and cisplatin via a superficial temporal artery for recurrent head and neck cancer to determine the optimal dose., Methods: The dose of cisplatin was fixed and the dose of docetaxel was escalated from 8 mg/m(2) , with an increase of 2 mg/m(2) per step, to identify the maximum tolerated dose (MTD). In total, 4 courses of weekly chemotherapy were administered., Results: Twelve patients were recruited to this trial. The MTD of docetaxel was 14 mg/m(2) . At this dose level, dose-limiting toxicity was observed in 2 of 3 patients. One patient experienced grade 3 leukopenia, while the other experienced grade 3 leukopenia. Myelosuppression was the dose-limiting toxicity for this regimen., Conclusion: The recommended dose for weekly arterial infusion of docetaxel was identified as 12 mg/m(2) combined with weekly cisplatin at 40 mg/m(2) , with 4 courses of each., (Copyright © 2011 Wiley Periodicals, Inc.)

To determine whether anticancer drugs delivered via arterial infusion can permeate entire tumors using a new MRI flow check method. We infused 20 ml of contrast medium (2 ml of Gd-GDPA plus 18 ml of normal saline) over a period of 10 min using a continuous injection pump, then immediately performed MRI using a 1.5 T unit. Images were obtained in 5-mm-thick continuous sections in two or three planes (axial, coronal, and sagittal) depending on the extent of the tumor, and enhanced fast gradient echo 3 D (EFGRE3D) images with a special inversion at lipids were photographed using a neurovascular array coil. The new MRI flow check method delineated an area of tongue cancer perfused with drugs more accurately than conventional methods.The MRI flow check method provides accurate information about areas of arterial infusion., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: Serum deoxyribonuclease I (DNase I) activity was reported to increase in the early phase after onset of acute myocardial infarction (AMI). Up to now, DNase I activity has been quantified by the single radial enzyme diffusion (SRED) method, which unfortunately requires a long incubation time. Therefore it is necessary to develop another assay suitable for measurement of serum DNase I concentrations in a clinical setting., Methods: A sandwich ELISA was established for measurement of DNase I protein using a polyclonal antibody directed against DNase I protein and a biotinylated monoclonal for subsequent detection. Concentrations of serum DNase I protein were measured in healthy individuals and patients with AMI., Results: This method was as precise as SRED, and took less time than SRED. A significant correlation was observed between DNase I concentration and enzyme activity (r=0.839; P<0.001). The average of serum DNase I in AMI patients within 0-12 h of chest pain was significantly higher than that in healthy individuals (P<0.001), and decreased with time., Conclusions: We have developed a sensitive ELISA capable of measuring DNase I protein concentrations. This method may be a useful alternative to SRED as an aid to diagnosis of AMI based on the serum DNase I level.

We have previously demonstrated that ischemia caused by acute myocardial infarction induces an abrupt increase of serum deoxyribonuclease I (DNase I) activity. In this study, we examined whether hypoxia can affect the levels of DNase I activity and/or its transcripts in vitro. We first exposed the human pancreatic cancer cell line QGP-1, which is the first documented DNase-I-producing cell line, to hypoxia (2% O2), and found that this induced a significant increase in both the activity and transcripts of DNase I. This response was mediated by increased transcription only from exon 1a of the two alternative transcription-initiating exons utilized simultaneously in the human DNase I gene (DNASE1); exposure of QGP-1 cells to hypoxia for 24 h resulted in a 15-fold increase of DNASE1 transcripts starting from exon 1a compared with the expression level under normoxic conditions. Promoter, electrophoretic mobility shift, and chromatin immunoprecipitation assays with QGP-1 cells exposed to hypoxia or normoxia showed that the region just upstream from exon 1a was involved in this response in a hypoxia-induced factor-1-independent, but at least in a Sp1 transcription factor-dependent manner possibly through enhanced binding of Sp1 protein to the promoter. These results indicate that DNASE1 expression is upregulated by hypoxia in the cells.

Levels of deoxyribonuclease I (DNase I) activity in vivo have been shown to be altered by physiological and/or pathological processes. However, no information is available on the regulation of DNase I gene (DNASE1) expression in vivo or in vitro. We first mapped the transcription start sites of DNASE1 in human pancreas and in the DNase I-producing human pancreatic cancer cell line QGP-1, and revealed a novel site approximately 12 kb upstream of exon 1, which was previously believed to be the single transcription-starting exon. This initiation site marks an alternative starting exon, designated 1a. Exons 1 and 1a were used simultaneously as transcription-starting exons in pancreas and QGP-1 cells. Promoter assay, EMSA and chromatin immunoprecipitation analysis with QGP-1 cells showed the promoter region of exon 1a in which the Sp1 transcription factor is specifically involved in promoter activity. This is the first to be identified as a transcription factor responsible for gene expression of vertebrate DNase I genes. Furthermore, RT-PCR analysis indicated alternative splicing of human DNASE1 pre-mRNA in pancreas and QGP-1 cells. Only two transcripts among eight alternative splicing products identified can be translated to produce intact DNase I protein. These results suggest that human DNASE1 expression is regulated through the use of alternative promoter and alternative splicing.