Survey on utilization of flattening filter-free photon beams in Japan

To understand the current state of flattening filter-free (FFF) beam implementation in C-arm linear accelerators (LINAC) in Japan, the quality assurance (QA)/quality control (QC) 2018–2019 Committee of the Japan Society of Medical Physics (JSMP) conducted a 37-question survey, designed to investigate facility information and specifications regarding FFF beam adoption and usage. The survey comprised six sections: facility information, devices, clinical usage, standard calibration protocols, modeling for treatment planning (TPS) systems and commissioning and QA/QC. A web-based questionnaire was developed. Responses were collected between 18 June and 18 September 2019. Of the 846 institutions implementing external radiotherapy, 323 replied. Of these institutions, 92 had adopted FFF beams and 66 had treated patients using them. FFF beams were used in stereotactic radiation therapy (SRT) for almost all disease sites, especially for the lungs using 6 MV and liver using 10 MV in 51 and 32 institutions, respectively. The number of institutions using FFF beams for treatment increased yearly, from eight before 2015 to 60 in 2018. Farmer-type ionization chambers were used as the standard calibration protocol in 66 (72%) institutions. In 73 (80%) institutions, the beam-quality conversion factor for FFF beams was calculated from TPR_20,10, via the same protocol used for beams with flattening filter (WFF). Commissioning, periodic QA and patient-specific QA for FFF beams also followed the procedures used for WFF beams. FFF beams were primarily used in high-volume centers for SRT. In most institutions, measurement and QA was conducted via the procedures used for WFF beams.     

Computerized estimation of patient setup errors in portal images based on localized pelvic templates for prostate cancer radiotherapy

We have developed a computerized method for estimating patient setup errors in portal images based on localized pelvic templates for prostate cancer radiotherapy. The patient setup errors were estimated based on a template-matching technique that compared the portal image and a localized pelvic template image with a clinical target volume produced from a digitally reconstructed radiography (DRR) image of each patient. We evaluated the proposed method by calculating the residual error between the patient setup error obtained by the proposed method and the gold standard setup error determined by consensus between two radiation oncologists. Eleven training cases with prostate cancer were used for development of the proposed method, and then we applied the method to 10 test cases as a validation test. As a result, the residual errors in the anterior–posterior, superior–inferior and left–right directions were smaller than 2 mm for the validation test. The mean residual error was 2.65 ± 1.21 mm in the Euclidean distance for training cases, and 3.10 ± 1.49 mm for the validation test. There was no statistically significant difference in the residual error between the test for training cases and the validation test (P = 0.438). The proposed method appears to be robust for detecting patient setup error in the treatment of prostate cancer radiotherapy.     

Fully automated rigid image registration versus human registration in postoperative spine stereotactic body radiation therapy: a multicenter non-inferiority study

To confirm the fully automated rigid image registration (A-RIR) accuracy in postoperative spine stereotactic body radiation therapy (SBRT), we conducted a multicenter non-inferiority study compared to the human rigid image registration (H-RIR). Twenty-eight metastatic cancer patients who underwent postoperative spine SBRT are enrolled—image registration (IR) of planning computed tomography (CT) and CT-myelogram for delineating the spinal cord. The adopted A-RIR workflow is a contour-focused algorithm performing a rigid registration by maximizing normalized mutual information (NMI) restricted to the data contained within the automatically extracted contour. Three radiation oncologists (ROs) from multicenters were prompted to review two blinded registrations and choose one for clinical use. Indistinguishable cases were allowed to vote equivalent, counted A-RIR side. A-RIR is considered non-inferior to H-RIR if the lower limit of the 95% confidence interval (CI) of A-RIR preferable/equivalent is greater than 0.45. We also evaluated the NMI improvement from the baseline and the translational/rotational errors between A-RIR and H-RIR. The A-RIR preferable/equivalent was selected in 21 patients (0.75, 95% CI: 0.55–0.89), demonstrating non-inferiority to H-RIR. The A-RIR’s NMI improvement was greater than H-RIR in 24 patients: the mean value ± SD was 0.225 ± 0.115 in A-RIR and 0.196 ± 0.114 in H-RIR (P < 0.001). The absolute translational error was 0.38 ± 0.31 mm. The rotational error was −0.03 ± 0.20, 0.05 ± 0.19, −0.04 ± 0.20 degrees in axial, coronal, and sagittal planes (range: −0.66–0.52). In conclusion, A-RIR shows non-inferior to H-RIR in CT and CT-myelogram registration for postoperative spine SBRT planning.     

Efficacy of FDG-PET for defining gross tumor volume of head and neck cancer

We analyzed the data for 53 patients with histologically proven primary squamous cell carcinoma of the head and neck treated with radiotherapy between February 2006 and August 2009. All patients underwent contrast-enhanced (CE)-CT and ¹⁸F-fluorodeoxyglucose (FDG)-PET before radiation therapy planning (RTP) to define the gross tumor volume (GTV). The PET-based GTV (PET-GTV) for RTP was defined using both CE-CT images and FDG-PET images. The CE-CT tumor volume corresponding to a FDG-PET image was regarded as the PET-GTV. The CE-CT-based GTV (CT-GTV) for RTP was defined using CE-CT images alone. Additionally, CT-GTV delineation and PET-GTV delineation were performed by four radiation oncologists independently in 19 cases. All four oncologists did both methods. Of these, PET-GTV delineation was successfully performed in all 19 cases, but CT-GTV delineation was not performed in 4 cases. In the other 15 cases, the mean CT-GTV was larger than the PET-GTV in 10 cases, and the standard deviation of the CT-GTV was larger than that of the PET-GTV in 10 cases. Sensitivity of PET-GTV for identifying the primary tumor was 96%, but that of CT-GTV was 81% (P < 0.01). In patients with oropharyngeal cancer and tongue cancer, the sensitivity of CT-GTV was 63% and 71%, respectively. When both the primary lesions and the lymph nodes were evaluated for RTP, PET-GTV differed from CT-GTV in 19 cases (36%). These results suggested that FDG-PET is effective for defining GTV in RTP for squamous cell carcinoma of the head and neck, and PET-GTV evaluated by both CE-CT and FDG-PET images is preferable to CT-GTV by CE-CT alone.     

Invasive Meningococcal Disease, 2011–2020, and Impact of the COVID-19 Pandemic,England

Invasive meningococcal disease incidence in England declined from 1.93/100,000 persons (1,016 cases) in 2010–11 to 0.95/100,000 (530 cases) in 2018–19 and 0.74/100,000 in 2019–20 (419 cases). During national lockdown for the coronavirus disease pandemic (April–August 2020), incidence was 75% lower than during April–August 2019.     

Effect of different treatment plans on irradiated small-bowel volume in gynecologic patients undergoing whole-pelvic irradiation

To evaluate the effect of different treatment plans for whole-pelvic irradiation on small-bowel volumes (SBVs) in patients with gynecologic malignancies, 40 patients were enrolled in this study. Computed tomography (CT) simulations were performed, and the small bowel of each patient was outlined manually. Treatment plans with equal-weighted (EW) and non-equal-weighted (NEW) (70% in bilateral directions) techniques of four-field and intensity-modulated radiation therapy (IMRT) were performed. The V10–V100 represented the volume (cm³) at different levels of the prescribed doses (10–100%). The V10–V100 was compared among the different treatment planning techniques, and patients who were suitable for IMRT or NEW were identified. IMRT and NEW significantly reduced the V50–V100 and V40–V60 levels compared with EW, respectively. NEW caused a significant reduction in the V30–V60 levels in patients with a BMI ≥26 kg/m². Patients with IMRT demonstrated lower V70–V100 levels compared with those with NEW. In patients with a BMI ≥26 kg/m² or an age ≥55 years, lower V20–V50 levels were noted using NEW compared with IMRT. Treatment planning with larger weighting in the bilateral directions in four-field radiotherapy reduces the low-dose SBV in patients with gynecologic malignancies, especially in those with a high BMI or the elderly. IMRT effectively reduces high-dose SBV, especially in patients with a low BMI.     

Methodological extensions of meta-analysis with excess relative risk estimates: application to risk of second malignant neoplasms among childhood cancer survivors treated with radiotherapy

Although radiotherapy is recognized as an established risk factor for second malignant neoplasms (SMNs), the dose response of SMNs following radiotherapy has not been well characterized. In our previous meta-analysis of the risks of SMNs occurring among children who have received radiotherapy, the small number of eligible studies precluded a detailed evaluation. Therefore, to increase the number of eligible studies, we developed a method of calculating excess relative risk (ERR) per Gy estimates from studies for which the relative risk estimates for several dose categories were available. Comparing the calculated ERR with that described in several original papers validated the proposed method. This enabled us to increase the number of studies, which we used to conduct a meta-analysis. The overall ERR per Gy estimate of radiotherapy over 26 relevant studies was 0.60 (95%CI: 0.30–1.20), which is smaller than the corresponding estimate for atomic bomb survivors exposed to radiation as young children (1.7; 95% CI: 1.1–2.5). A significant decrease in ERR per Gy with increase in age at exposure (0.85 times per annual increase) was observed in the meta-regression. Heterogeneity was suggested by Cochran''s Q statistic (P < 0.001), which may be partly accounted for by age at exposure.     

内蒙古医用电子直线加速器放疗资源现状

目的 调查内蒙古地区放疗资源现状,为优化资源配置和放疗技术科学发展提供参考依据。方法 采用多种方式对设备、人员分配的不同情况进行调查和分析。结果 截止2014年12月,内蒙古地区共在役30台医用电子直线加速器和1台⁶⁰Co远距离治疗机。开展医用电子直线加速器放疗工作的单位有26家和⁶⁰Co远距离放疗的1家;相关放疗医务人员(不包括部队系统医院放疗医务人员)共176人。结论 放疗资源配置不尽均衡。普遍缺乏放疗医师、物理师和技师等相关技术人员,人才培养亟待加强。     

Results and DVH analysis of late rectal bleeding in patients treated with 3D-CRT or IMRT for localized prostate cancer

In patients undergoing radiotherapy for localized prostate cancer, dose–volume histograms and clinical variables were examined to search for correlations between radiation treatment planning parameters and late rectal bleeding. We analyzed 129 patients with localized prostate cancer who were managed from 2002 to 2010 at our institution. They were treated with 3D conformal radiation therapy (3D-CRT, 70 Gy/35 fractions, 55 patients) or intensity-modulated radiation therapy (IMRT, 76 Gy/38 fractions, 74 patients). All radiation treatment plans were retrospectively reconstructed, dose–volume histograms of the rectum were generated, and the doses delivered to the rectum were calculated. Time to rectal bleeding ranged from 9–53 months, with a median of 18.7 months. Of the 129 patients, 33 patients had Grade 1 bleeding and were treated with steroid suppositories, while 25 patients with Grade 2 bleeding received argon plasma laser coagulation therapy (APC). Three patients with Grade 3 bleeding required both APC and blood transfusion. The 5-year incidence rate of Grade 2 or 3 rectal bleeding was 21.8% for the 3D-CRT group and 21.6% for the IMRT group. Univariate analysis showed significant differences in the average values from V65 to V10 between Grades 0–1 and Grades 2–3. Multivariate analysis demonstrated that patients with V65 ≥ 17% had a significantly increased risk (P = 0.032) of Grade 2 or 3 rectal bleeding. Of the 28 patients of Grade 2 or 3 rectal bleeding, 17 patients (60.7%) were cured by a single session of APC, while the other 11 patients required two sessions. Thus, none of the patients had any further rectal bleeding after the second APC session.     

Sensitivity of Food-Based Recommendations Developed Using Linear Programming to Model Input Data in Young Kenyan Children

Food-based recommendations (FBR) developed using linear programming generally use dietary intake and energy and nutrient requirement data. It is still unknown to what extent the availability and selection of these data affect the developed FBR and identified problem nutrients. We used 24 h dietary recalls of 62 Kenyan children (4–6 years of age) to analyse the sensitivity of the FBR and problem nutrients to (1) dietary intake data, (2) selection criteria applied to these data and (3) energy and nutrient requirement data, using linear programming (Optifood©), by comparing a reference scenario with eight alternative scenarios. Replacing reported by estimated consumption frequencies increased the recommended frequencies in the FBR for most food groups while folate was no longer identified as a problem nutrient. Using the 10–90th instead of the 5–95th percentile of distribution to define minimum and maximum frequencies/week decreased the recommended frequencies in the FBR and doubled the number of problem nutrients. Other alternative scenarios negligibly affected the FBR and identified problem nutrients. Our study shows the importance of consumption frequencies for developing FBR and identifying problem nutrients by linear programming. We recommend that reported consumption frequencies and the 5–95th percentiles of distribution of reported frequencies be used to define the minimum and maximum frequencies.     

Automatic contour segmentation of cervical cancer using artificial intelligence

In cervical cancer treatment, radiation therapy is selected based on the degree of tumor progression, and radiation oncologists are required to delineate tumor contours. To reduce the burden on radiation oncologists, an automatic segmentation of the tumor contours would prove useful. To the best of our knowledge, automatic tumor contour segmentation has rarely been applied to cervical cancer treatment. In this study, diffusion-weighted images (DWI) of 98 patients with cervical cancer were acquired. We trained an automatic tumor contour segmentation model using 2D U-Net and 3D U-Net to investigate the possibility of applying such a model to clinical practice. A total of 98 cases were employed for the training, and they were then predicted by swapping the training and test images. To predict tumor contours, six prediction images were obtained after six training sessions for one case. The six images were then summed and binarized to output a final image through automatic contour segmentation. For the evaluation, the Dice similarity coefficient (DSC) and Hausdorff distance (HD) was applied to analyze the difference between tumor contour delineation by radiation oncologists and the output image. The DSC ranged from 0.13 to 0.93 (median 0.83, mean 0.77). The cases with DSC <0.65 included tumors with a maximum diameter < 40 mm and heterogeneous intracavitary concentration due to necrosis. The HD ranged from 2.7 to 9.6 mm (median 4.7 mm). Thus, the study confirmed that the tumor contours of cervical cancer can be automatically segmented with high accuracy.     

Five-fraction CyberKnife radiotherapy for large brain metastases in critical areas: impact on the surrounding brain volumes circumscribed with a single dose equivalent of 14 Gy (V14) to avoid radiation necrosis

The efficacy and toxicity of five-fraction CyberKnife radiotherapy were evaluated in patients with large brain metastases in critical areas. A total of 85 metastases in 78 patients, including tumors >30 cm³ (4 cm in diameter) were treated with five-fraction CyberKnife radiotherapy with a median marginal dose of 31 Gy at a median prescribed isodose of 58%. Changes in the neurological manifestations, local tumor control, and adverse effects were investigated after treatment. The surrounding brain volumes circumscribed with 28.8 Gy (single dose equivalent to 14 Gy: V14) were measured to evaluate the risk of radiation necrosis. Neurological manifestations, such as motor weakness, visual disturbances and aphasia improved in 28 of 55 patients (50.9%). Local tumor control was obtained in 79 of 85 metastases (92.9%) during a median follow-up of eight months. Symptomatic edema occurred in 10 patients, and two of them (2.6%) required surgical resection because of radiation necrosis. The V14 of these patients was 3.0–19.7 cm³. There were 16 lesions with a V14 of ≥7.0 cm³, and two of these lesions developed extensive brain edema due to radiation necrosis. None of the patients with a V14 of <7.0 cm³ exhibited edema requiring surgical intervention. We therefore conclude that a high rate of local tumor control and low rates of complications can be obtained after five-fraction CyberKnife radiotherapy for large metastases in critical areas. The V14 of the surrounding brain is therefore a useful indicator for the risk of radiation necrosis in patients with large metastases.     

Validity of reduced radiation dose for localized diffuse large B-cell lymphoma showing a good response to chemotherapy

To evaluate the validity of a decrease in the radiation dose for patients who were good responders to chemotherapy for localized diffuse large B-cell lymphoma (DLBCL), 91 patients with localized DLBCL who underwent radiotherapy after multi-agent chemotherapy from 1988–2008 were reviewed. Exclusion criteria were as follows: central nervous system or nasal cavity primary site, or Stage II with bulky tumor (≥10 cm). Of these patients, 62 were identified as good responders to chemotherapy. They were divided into two groups receiving either a higher or a lower radiation dose (32–50.4 Gy or 15–30.6 Gy, respectively). There were no statistically significant differences between the lower and higher dose groups in progression-free survival, locoregional progression-free survival or overall survival. Adaptation of decreased radiation dose may be valid for localized DLBCL patients who show a good response to chemotherapy.     

Prognostic significance of inflammatory response markers for locally advanced squamous cell carcinoma of the external auditory canal and middle ear

We investigated the prognostic significance and treatment outcomes of pretreatment inflammatory response markers for locally advanced squamous cell carcinoma (SCC) of the external auditory canal (EAC) and middle ear (ME). Between July 2003 and July 2019, 21 patients with SCC of the EAC (n = 18) or ME (n = 3) who received radiotherapy with or without surgery or systemic therapy (radiotherapy alone [n = 2], radiotherapy + systemic therapy [n = 6], radiotherapy + surgery [n = 7], radiotherapy + surgery + systemic therapy [n = 6]) were retrospectively examined. The median radiation dose was 66.0 (range, 50.4–70.0) Gy, with daily fractions of 1.8–2.0 Gy. The median follow-up period was 25 months (range, 6–137). The two-year overall survival (OS), progression-free survival (PFS), and locoregional control (LC) rates were 61%, 48%, and 55%, respectively. OS, PFS, and LC did not differ significantly according to patient- (age, sex), tumor- (Pittsburgh stage, pretreatment neurological findings), and treatment-related (surgery or systemic therapy, radiation dose, prophylactic neck irradiation) factors. Conversely, there were significant differences in OS, PFS, and LC between patients with high and low pretreatment C-reactive protein-to-albumin ratios (p = 0.002, 0.003, and 0.004, respectively). OS also differed significantly between patients with high and low pretreatment neutrophil-to-lymphocyte ratios (NLR; p = 0.037). Other inflammatory response markers, including platelet-to-lymphocyte ratio (PLR) and albumin-to-globulin ratio (AGR), did not influence OS, PFS, or LC. Our findings suggest that pretreatment C-reactive protein-to-albumin ratio and NLRs have a significant impact on treatment outcomes in patients with locally advanced SCC of the EAC and ME.     

The emerging role of high-dose-rate (HDR) brachytherapy as monotherapy for prostate cancer

High-dose-rate (HDR) brachytherapy as monotherapy is a comparatively new brachytherapy procedure for prostate cancer. In addition to the intrinsic advantages of brachytherapy, including radiation dose concentration to the tumor and rapid dose fall-off at the surrounding normal tissue, HDR brachytherapy can yield a more homogeneous and conformal dose distribution through image-based decisions for source dwell positions and by optimization of individual source dwell times. Indication can be extended even to T3a/b or a part of T4 tumors because the applicators can be positioned at the extracapsular lesion, into the seminal vesicles, and/or into the bladder, without any risk of source migration or dropping out. Unlike external beam radiotherapy, with HDR brachytherapy inter-/intra-fraction organ motion is not problematic. However, HDR monotherapy requires patients to stay in bed for 1–4 days during hospitalization, even though the actual overall treatment time is short. Recent findings that the α/β value for prostate cancer is less than that for the surrounding late-responding normal tissue has made hypofractionation attractive, and HDR monotherapy can maximize this advantage of hypofractionation. Research on HDR monotherapy is accelerating, with a growing number of publications reporting excellent preliminary clinical results due to the high ‘biologically effective dose (BED)’ of >200 Gy. Moreover, the findings obtained for HDR monotherapy as an early model of extreme hypofractionation tend to be applied to other radiotherapy techniques such as stereotactic radiotherapy. All these developments point to the emerging role of HDR brachytherapy as monotherapy for prostate cancer.     

2016 - 2018年天津市职业外照射个人剂量监测结果分析

目的 分析天津市放射工作人员外照射个人剂量监测基本情况。方法　采用方便抽样方法,以2016 - 2018年582家单位进行个人剂量监测的放射工作人员为调查对象,分析连续3年的监测数据。结果　3年连续共监测放射工作人员11 790人次, 年集体有效剂量1 649.55人.mSv,人均年有效剂量为0.07 mSv/a。2016年和2018年均高于2017年年人均有效剂量,差异有统计学意义（Ｈ = 201.04,P＜0.01）。用人单位4个周期监测率,二级医院最高,非医疗机构最低,差异有统计学意义（χ2 = 949.68,P＜0.01）。两两比较显示,核医学和牙科放射人均年有效剂量最高,其次为诊断放射学和放射治疗学,差异均有统计学意义（P＜0.05）。结论　天津市放射工作人员年有效剂量基本符合职业接触人群个人剂量当量年限值的要求。加强三级医疗机构、非医疗机构监管和核医学、诊断放射学和放射治疗学人员的放射危害防护。     

Validation of dose distribution for liver tumors treated with real-time-image gated spot-scanning proton therapy by log data based dose reconstruction

In spot scanning proton therapy (SSPT), the spot position relative to the target may fluctuate through tumor motion even when gating the radiation by utilizing a fiducial marker. We have established a procedure that evaluates the delivered dose distribution by utilizing log data on tumor motion and spot information. The purpose of this study is to show the reliability of the dose distributions for liver tumors treated with real-time-image gated SSPT (RGPT). In the evaluation procedure, the delivered spot information and the marker position are synchronized on the basis of log data on the timing of the spot irradiation and fluoroscopic X-ray irradiation. Then a treatment planning system reconstructs the delivered dose distribution. Dose distributions accumulated for all fractions were reconstructed for eight liver cases. The log data were acquired in all 168 fractions for all eight cases. The evaluation was performed for the values of maximum dose, minimum dose, D99, and D5–D95 for the clinical target volumes (CTVs) and mean liver dose (MLD) scaled by the prescribed dose. These dosimetric parameters were statistically compared between the planned dose distribution and the reconstructed dose distribution. The mean difference of the maximum dose was 1.3% (95% confidence interval [CI]: 0.6%—2.1%). Regarding the minimum dose, the mean difference was 0.1% (95% CI: −0.5%—0.7%). The mean differences of D99, D5–D95 and MLD were below 1%. The reliability of dose distributions for liver tumors treated with RGPT-SSPT was shown by the evaluation of the accumulated dose distributions.     

Radiotherapy for gastric lymphoma: a planning study of 3D conformal radiotherapy,the half-beam method,and intensity-modulated radiotherapy

During radiotherapy for gastric lymphoma, it is difficult to protect the liver and kidneys in cases where there is considerable overlap between these organs and the target volume. This study was conducted to compare the three radiotherapy planning techniques of four-fields 3D conformal radiotherapy (3DCRT), half-field radiotherapy (the half-beam method) and intensity-modulated radiotherapy (IMRT) used to treat primary gastric lymphoma in which the planning target volume (PTV) had a large overlap with the left kidney. A total of 17 patients with gastric diffuse large B-cell lymphoma (DLBCL) were included. In DLBCL, immunochemotherapy (Rituximab + CHOP) was followed by radiotherapy of 40 Gy to the whole stomach and peri-gastric lymph nodes. 3DCRT, the half-field method, and IMRT were compared with respect to the dose–volume histogram (DVH) parameters and generalized equivalent uniform dose (gEUD) to the kidneys, liver and PTV. The mean dose and gEUD for 3DCRT was higher than for IMRT and the half-beam method in the left kidney and both kidneys. The mean dose and gEUD of the left kidney was 2117 cGy and 2224 cGy for 3DCRT, 1520 cGy and 1637 cGy for IMRT, and 1100 cGy and 1357 cGy for the half-beam method, respectively. The mean dose and gEUD of both kidneys was 1335 cGy and 1559 cGy for 3DCRT, 1184 cGy and 1311 cGy for IMRT, and 700 cGy and 937 cGy for the half-beam method, respectively. Dose–volume histograms (DVHs) of the liver revealed a larger volume was irradiated in the dose range <25 Gy with 3DCRT, while the half-beam method irradiated a larger volume of liver with the higher dose range (>25 Gy). IMRT and the half-beam method had the advantages of dose reduction for the kidneys and liver.