A Japanese multi-institutional phase II study of moderate hypofractionated intensity-modulated radiotherapy with image-guided technique for prostate cancer.

BACKGROUND: The aim of this multi-institutional phase II study was to confirm the safety and the potential efficacy of moderately hypofractionated intensity-modulated radiotherapy (IMRT) with prostate-based image-guidance for Japanese patients. METHODS: Patients with low- or intermediate-risk localized prostate cancer were eligible. Patients with a part of high risk (having only one of the following factors, cT3a, 20 < PSA ≤ 30, or GS = 8 or 9) were also included. Hypofractionated IMRT using daily image-guided technique with prostate matching was performed with a total dose of 70 Gy in 28 fractions. Neoadjuvant hormonal therapy for 4-8 months was mandatory for patients with intermediate or high-risk prostate cancer. RESULTS: From 20 institutions, 134 patients enrolled. The median follow-up was 5.16 years (range, 1.43-6.47 years). The number of patients with low, intermediate, and high-risk prostate cancer was 20, 80, and 34, respectively. The 5-year overall, biochemical failure-free, and clinical failure-free survival was 94.5%, 96.0%, and 99.2%, respectively. The 5-year biochemical failure-free survival for patients with low-, intermediate-, and high-risk disease was 94.1%, 97.4%, and 93.9%, respectively. The incidences of grade 2 gastrointestinal (GI) and genitourinary (GU) late toxicities at 5 years were 5.3% and 5.3%, respectively. There are no acute or late toxicities ≥ grade 3. Of 124 patients who were followed for up to 5 years, the grade 2 late GU or GI toxicities were 10.5% (90% confidence intervals, 6.3-16.2%, p = 0.0958). CONCLUSION: The safety and efficacy of moderately hypofractionated IMRT with prostate-based image-guidance was confirmed among Japanese patients with prostate cancer.

Interim Report of a Japanese Phase II Trial for Cardiac Stereotactic Body Radiotherapy in Refractory Ventricular Tachycardia　- Focus on Target Determination.

Background: Cardiac radiotherapy using stereotactic body radiation therapy (SBRT) has attracted attention as a minimally invasive treatment for refractory ventricular tachycardia. However, a standardized protocol and software program for determining the irradiation target have not been established. Here, we report the first preclinical stereotactic radioregulation antiarrhythmic therapy trial in Japan, focused on the target-setting process. Methods and Results: From 2019 onwards, 3 patients (age range 60-91 years) presenting with ischemic or non-ischemic cardiomyopathy were enrolled. Two patients were extremely serious and urgent, and were followed up for 6 and 30 months. To determine the irradiation targets, we aggregated electrophysiological, structural, and functional data and reflected them in an American Heart Association 17-segment model, as per the current recommendations. However, in all 3 patients, invasive electrophysiological study, phase-contrast computed tomography, and magnetic resonance imaging could not be performed; therefore, electrophysiological and structural information was limited. As alternatives, high-resolution ambulatory electrocardiography and nuclear medicine studies were useful in assessing arrhythmic substrates; however, concerns regarding test weighting and multiple scoring remain. Risks to surrounding organs were fully taken into account. Conclusions: In patients requiring cardiac SBRT, the information needed for target planning is sometimes limited to minimally invasive tests. Although there are issues to be resolved, this is a promising option for the life-saving treatment of patients in critical situations.

Effect on Heart and Lung Doses Reduction of Abdominal and Thoracic Deep Inspiratory Breath-hold Assuming Involved-field Radiation Therapy in Patients with Simulated Esophageal Cancer.

PURPOSE: The purpose of this study was to evaluate the lung and heart doses in volumetric-modulated arc therapy (VMAT) using involved-field irradiation in patients with middle-to-lower thoracic esophageal cancer during free breathing (FB), abdominal deep inspiratory breath-hold (A-DIBH), and thoracic DIBH (T-DIBH) images. METHODS: Computed tomography images of A-DIBH, T-DIBH, and FB from 25 patients with breast cancer were used to simulate patients with esophageal cancer. The irradiation field was set at an involved-field, and target and risk organs were outlined according to uniform criteria. VMAT optimization was performed, and lung and heart doses were evaluated. RESULTS: A-DIBH had a lower lung V20 Gy than FB and a lower lung V40 Gy, V30 Gy, V20 Gy than T-DIBH. The heart all dose indices were lower in T-DIBH than FB, and the heart V10 Gy was lower in A-DIBH than FB. However, the heart Dmean was comparable with A-DIBH and T-DIBH. CONCLUSIONS: A-DIBH had significant dose advantages for lungs compared to FB and T-DIBH, and the heart Dmean was comparable to T-DIBH. Therefore, when performing DIBH, A-DIBH is suggested for radiotherapy in patients with middle-to-lower thoracic esophageal cancer, excluding irradiation of the prophylactic area.

Dose and organ displacement comparisons with breast conservative radiotherapy using abdominal and thoracic deep-inspiration breath-holds: A comparative dosimetric study.

Deep-inspiration breath-hold (DIBH) reduces the radiation dose to the heart and lungs during breast radiotherapy in cancer. However, there is not enough discussion about suitable breathing methods for DIBH. Therefore, we investigated the radiation doses and organ and body surface displacement in abdominal DIBH (A-DIBH) and thoracic DIBH (T-DIBH). Free-breathing, A-DIBH, and T-DIBH computed tomography images of 100 patients were used. After contouring the targets, heart, and lungs, radiotherapy plans were created. We investigated the heart and lung doses, the associations between the heart and left lung displacements, and the thorax and abdominal surface displacements. No significant differences were observed in the target dose indices. However, the heart and lung doses were significantly lower in A-DIBH than in T-DIBH for all the indices; the mean heart and lung doses were 1.69 and 3.48 Gy, and 1.91 and 3.55 Gy in A-DIBH and T-DIBH, respectively. The inferior displacement of the heart and the left lung was more significant in A-DIBH. Therefore, inferior expansion of the heart and lungs may be responsible for the respective dose reductions. The abdominal surface displaced more than the thoracic surface in both A-DIBH and T-DIBH, and thoracic surface displacement was greater in T-DIBH than in A-DIBH. Moreover, A-DIBH can be identified because abdominal surface displacement was greater in A-DIBH than in T-DIBH. In conclusion, A-DIBH and T-DIBH could be distinguished by comparing the abdominal and thoracic surfaces of A-DIBH and T-DIBH, thereby ensuring the implementation of A-DIBH and reducing the heart and lung doses.

Heavy Ion Irradiation Reduces Vulnerability to Atrial Tachyarrhythmias　- Gap Junction and Sympathetic Neural Remodeling.

BACKGROUND: Low-invasive stereotactic body radiation therapy is a novel anti-arrhythmic strategy. The mechanisms underlying its effects against ventricular tachycardia/fibrillation (VT/VF) are gradually becoming clear, whereas those underlying atrial tachycardia/fibrillation (AT/AF) remain unknown. This study investigated the effects of carbon ion beam on gap junction expression and sympathetic innervation.Methods and Results: Atrial and ventricular tachyarrhythmia models was established in 26 hypercholesterolemic (HC) 3-year-old New Zealand white rabbits; 12 rabbits were irradiated with a single 15-Gy carbon ion beam (targeted heavy ion irradiation [THIR]) and 14 were not (HC group). Eight 3-month-old rabbits (Young) were used as a reference group. In vivo induction frequencies in the Young, HC, and HC+THIR groups were 0%, 9.9%, and 1.2%, respectively, for AT/AF and 0%, 7.8%, and 1.2%, respectively, for VT/VF (P<0.01). The conduction velocity of the atria and ventricles on optical mapping was significantly reduced in the HC group; this was reversed in the HC+THIR group. Connexin-40 immunolabelling in the atria was 66.1-78.7% lower in the HC than Young group; this downregulation was less pronounced in the HC+THIR group (by 23.1-44.4%; P<0.01). Similar results were obtained for ventricular connexin-43. Sympathetic nerve densities in the atria and ventricles increased by 41.9-65.3% in the HC vs. Young group; this increase was reversed in the HC+THIR group. CONCLUSIONS: Heavy ion radiation reduced vulnerability to AT/AF and VT/VF in HC elderly rabbits and improved cardiac conductivity. The results suggest involvement of connexin-40/43 upregulation and suppression of sympathetic nerve sprouting.

Examination of the dose distribution of volumetric modulated arc radiotherapy using a high-definition multi-leaf collimator for breast cancer patients with irradiated regional lymph nodes.

Background: A high-definition multi-leaf collimator (HD-MLC) with 5- and 10-mm fine MLCs is useful for radiotherapy. However, it is difficult to irradiate the mammary gland and supraclavicular region using a HD-MLC because of the narrow field of volumetric modulated arc radiotherapy (VMAT). Therefore, we aimed to evaluate the dose distribution of the VMAT dose using a HD-MLC in 15 patients with left breast cancer undergoing postoperative irradiation of breast and regional lymph nodes, including the internal mammary node. Materials and methods: The following four plans were generated: three-arc VMAT using HD-MLC (HD-VMAT), two tangential arcs and one-arc VMAT using HD-MLC (tHD-VMAT), three-dimensional conformal radiotherapy (3DCRT) using HD-MLC, and two-arc VMAT using the Millennium 120-leaf MLC (M-VMAT). We assessed the doses to the target volume and organs at risk. Results: The target dose distributions were higher for HD-VMAT than 3DCRT. There were no significant differences in the heart mean dose (Dmean) or lung volume receiving 20 Gy (V20 Gy) between HD-VMAT and 3DCRT. The heart Dmean and lung V20 Gy of tHD-VMAT were higher than those of HD-VMAT, and the heart Dmean of M-VMAT was higher than that of HD-VMAT. However, the target doses of tHD-VMAT, M-VMAT, and HD-VMAT were equivalent. Conclusions: In cases of the mammary gland and regional lymph node irradiation, including the internal mammary node in patients with left breast cancer, HD-VMAT was not inferior to M-VMAT and provided a better dose distribution to the target volume and organs at risk compared with 3DCRT and tHD-VMAT.

Comparing the toxicity and disease control rate of radiotherapy for prostate cancer between salvage settings after high-intensity focused ultrasound therapy and initial settings.

The purpose of this retrospective study was to compare the toxicity and disease control rate of radiotherapy for prostate cancer in salvage settings after high-intensity focused ultrasound (HIFU) therapy (HIFU cohort) with those in radical settings (non-HIFU cohort). From 2012 to 2020, 215 patients were identified for this study and 17 were treated in the salvage settings after HIFU. The median follow-up time was 34.5 months (range: 7-102 months, inter-quartile range [IQR]: 16-64 months). Genitourinary (GU) and gastrointestinal (GI) adverse events were evaluated in acute and late periods with Common Terminology Criteria for Adverse Events version 5, and the rates of biochemical-clinical failure free survival (BCFS) and overall survival (OS) were estimated. The cumulative incidence of late GU Grade 2 or greater toxicity after five years was significantly different between the non-HIFU and HIFU cohorts with rates of 7.3% and 26.2%, respectively (P = 0.03). Regarding GI Grade 2 or greater toxicity, there was no significant difference between the two cohorts. The 5y-BCFS was 84.2% in the non-HIFU cohort and 69.5% in the HIFU cohort with no significant difference (P = 0.10) and the 5y-OS was 95.9% and 92.3%, respectively (P = 0.47). We concluded that the possibility of increased late GU Grade 2 or greater should be considered when applying salvage radiotherapy for local recurrence after HIFU.

Applying Artificial Neural Networks to Develop a Decision Support Tool for Tis-4N0M0 Non-Small-Cell Lung Cancer Treated With Stereotactic Body Radiotherapy.

PURPOSE: Clear evidence indicating whether surgery or stereotactic body radiation therapy (SBRT) is best for non-small-cell lung cancer (NSCLC) is lacking. SBRT has many advantages. We used artificial neural networks (NNs) to predict treatment outcomes for patients with NSCLC receiving SBRT, aiming to aid in decision making. PATIENTS AND METHODS: Among consecutive patients receiving SBRT between 2005 and 2019 in our institution, we retrospectively identified those with Tis-T4N0M0 NSCLC. We constructed two NNs for prediction of overall survival (OS) and cancer progression in the first 5 years after SBRT, which were tested using an internal and an external test data set. We performed risk group stratification, wherein 5-year OS and cancer progression were stratified into three groups. RESULTS: In total, 692 patients in our institution and 100 patients randomly chosen in the external institution were enrolled. The NNs resulted in concordance indexes for OS of 0.76 (95% CI, 0.73 to 0.79), 0.68 (95% CI, 0.60 to 0.75), and 0.69 (95% CI, 0.61 to 0.76) and area under the curve for cancer progression of 0.80 (95% CI, 0.75 to 0.84), 0.72 (95% CI, 0.60 to 0.83), and 0.70 (95% CI, 0.57 to 0.81) in the training, internal test, and external test data sets, respectively. The survival and cumulative incidence curves were significantly stratified. NNs selected low-risk cancer progression groups of 5.6%, 6.9%, and 7.0% in the training, internal test, and external test data sets, respectively, suggesting that 48% of patients with peripheral Tis-4N0M0 NSCLC can be at low-risk for cancer progression. CONCLUSION: Predictions of SBRT outcomes using NNs were useful for Tis-4N0M0 NSCLC. Our results are anticipated to open new avenues for NN predictions and provide decision-making guidance for patients and physicians.

Effects of sample size and data augmentation on U-Net-based automatic segmentation of various organs.

Deep learning has demonstrated high efficacy for automatic segmentation in contour delineation, which is crucial in radiation therapy planning. However, the collection, labeling, and management of medical imaging data can be challenging. This study aims to elucidate the effects of sample size and data augmentation on the automatic segmentation of computed tomography images using U-Net, a deep learning method. For the chest and pelvic regions, 232 and 556 cases are evaluated, respectively. We investigate multiple conditions by changing the sum of the training and validation datasets across a broad range of values: 10-200 and 10-500 cases for the chest and pelvic regions, respectively. A U-Net is constructed, and horizontal-flip data augmentation, which produces left and right inverse images resulting in twice the number of images, is compared with no augmentation for each training session. All lung cases and more than 100 prostate, bladder, and rectum cases indicate that adding horizontal-flip data augmentation is almost as effective as doubling the number of cases. The slope of the Dice similarity coefficient (DSC) in all organs decreases rapidly until approximately 100 cases, stabilizes after 200 cases, and shows minimal changes as the number of cases is increased further. The DSCs stabilize at a smaller sample size with the incorporation of data augmentation in all organs except the heart. This finding is applicable to the automation of radiation therapy for rare cancers, where large datasets may be difficult to obtain.

Verification of the junctional dose for irradiation of the chest wall and supraclavicular regions under the circumstances of advanced technologies.

A single-isocenter half-beam technique is commonly used when irradiating the chest wall and supraclavicular regions in patients with high-risk breast cancer. However, several studies have reported that underdosage can occur at the junction of the chest wall and supraclavicular regions due to a "tongue-and-groove" effect. This study verified the efficacy of an open leaf technique (OL-tech) that involves placing a multileaf collimator 5 mm outside from the beam central axis to remove the effect of the multileaf collimator in a single-isocenter half-beam technique. We compared the junction doses of the OL-tech with those of a conventional technique (C-tech) in square and clinical plans, using 4 and 10 MV x-rays in the Clinac iX and 6 and 10 MV x-rays in the Trilogy accelerators (Varian Medical Systems, Palo Alto, CA). EBT3 radiochromic films were used for measurements. Measurements were performed at a depth of 3 cm when verifying field matching. The EBT3 films in the square plan indicated junction doses for the C-tech of 78.3% with the Clinac iX accelerator and 73.6% with the Trilogy accelerator. By contrast, the corresponding doses for the OL-tech were 107.2% and 99.8%, respectively. In the clinical plan, the junction doses for the C-tech were 76.5% with the Clinac iX accelerator and 72.6% with the Trilogy accelerator; the corresponding doses for the OL-tech were 108.3% and 101.7%, respectively. As with the square plan, variations in the junction dose were much smaller using the OL-tech than using the C-tech. Our results suggest that the OL-tech can be useful for improving dose homogeneity at the junction of the chest wall and supraclavicular regions.

Simple low-cost approaches to semantic segmentation in radiation therapy planning for prostate cancer using deep learning with non-contrast planning CT images.

PURPOSE: Deep learning has shown great efficacy for semantic segmentation. However, there are difficulties in the collection, labeling and management of medical imaging data, because of ethical complications and the limited number of imaging studies available at a single facility. This study aimed to find a simple and low-cost method to increase the accuracy of deep learning semantic segmentation for radiation therapy of prostate cancer. METHODS: In total, 556 cases with non-contrast CT images for prostate cancer radiation therapy were examined using a two-dimensional U-Net. Initially, all slices were used for the input data. Then, we removed slices of the cranial portions, which were beyond the margins of the bladder and rectum. Finally, the ground truth labels for the bladder and rectum were added as channels to the input for the prostate training dataset. RESULTS: The highest mean dice similarity coefficients (DSCs) for each organ in the test dataset of 56 cases were 0.85 ± 0.05, 0.94 ± 0.04 and 0.85 ± 0.07 for the prostate, bladder and rectum, respectively. Removal of the cranial slices from the original images significantly increased the DSC of the rectum from 0.83 ± 0.09 to 0.85 ± 0.07 (p < 0.05). Adding bladder and rectum information to prostate training without removing the slices significantly increased the DSC of the prostate from 0.79 ± 0.05 to 0.85 ± 0.05 (p < 0.05). CONCLUSIONS: These cost-free approaches may be useful for new applications, which may include updated models and datasets. They may be applicable to other organs at risk (OARs) and clinical targets such as elective nodal irradiation.

Dosimetric study of whole-brain irradiation with high-energy photon beams for dose reduction to the scalp.

OBJECTIVE: To evaluate the efficiency of high-energy photons for mitigating alopecia due to whole-brain irradiation (WBRT). METHODS: Planning CT data from 10 patients who received WBRT were collected. We prepared 4 WBRT plans that used 6 or 15 MV photon beams, with or without use of a field-in-field (FiF) technique, and compared outcomes using a treatment planning system. The primary outcome was dose parameters to the scalp, including the mean dose, maximum dose, and dose received to 50% scalp(D50%). Secondary outcomes were minimum dose to the brain surface. RESULTS: Using FiF, the mean doses were 24.4-26.0 and 22.4-24.1 Gy, and the maximum doses were 30.5-32.1 and 28.5-30.8 Gy for 6 and 15 MV photon beams, respectively. Without FiF, the mean doses were 24.6-26.9 and 22.6-24.5 Gy, and the maximum doses were 30.8-34.6 and 28.6-32.4 Gy for 6 and 15 MV photon beams. The 15 MV plan resulted in a lower scalp dose for each dose parameter (p < 0.001). Using FiF, the minimum doses to the brain surface for the 6 and 15 MV plans were 28.9 ± 0.440 and 29.0 ± 0.557 Gy, respectively (p = 0.70). Without FiF, the minimum doses to the brain surface for the 6 and 15 MV plans were 28.9 ± 0.456 and 29.0 ± 0.529, respectively (p = 0.66). CONCLUSION: Compared with the 6 MV plan, the 15 MV plan achieved a lower scalp dose without impairing the brain surface dose. ADVANCES IN KNOWLEDGE: High-energy photon WBRT may mitigate alopecia of patients who receiving WBRT.

Efficacy evaluation of 2D, 3D U-Net semantic segmentation and atlas-based segmentation of normal lungs excluding the trachea and main bronchi.

This study aimed to examine the efficacy of semantic segmentation implemented by deep learning and to confirm whether this method is more effective than a commercially dominant auto-segmentation tool with regards to delineating normal lung excluding the trachea and main bronchi. A total of 232 non-small-cell lung cancer cases were examined. The computed tomography (CT) images of these cases were converted from Digital Imaging and Communications in Medicine (DICOM) Radiation Therapy (RT) formats to arrays of 32 × 128 × 128 voxels and input into both 2D and 3D U-Net, which are deep learning networks for semantic segmentation. The number of training, validation and test sets were 160, 40 and 32, respectively. Dice similarity coefficients (DSCs) of the test set were evaluated employing Smart SegmentationⓇ Knowledge Based Contouring (Smart segmentation is an atlas-based segmentation tool), as well as the 2D and 3D U-Net. The mean DSCs of the test set were 0.964 [95% confidence interval (CI), 0.960-0.968], 0.990 (95% CI, 0.989-0.992) and 0.990 (95% CI, 0.989-0.991) with Smart segmentation, 2D and 3D U-Net, respectively. Compared with Smart segmentation, both U-Nets presented significantly higher DSCs by the Wilcoxon signed-rank test (P < 0.01). There was no difference in mean DSC between the 2D and 3D U-Net systems. The newly-devised 2D and 3D U-Net approaches were found to be more effective than a commercial auto-segmentation tool. Even the relatively shallow 2D U-Net which does not require high-performance computational resources was effective enough for the lung segmentation. Semantic segmentation using deep learning was useful in radiation treatment planning for lung cancers.

Inter-fractional variations in the dosimetric parameters of accelerated partial breast irradiation using a strut-adjusted volume implant.

The aim of the study was to evaluate inter-fractional dosimetric variations for high-dose rate breast brachytherapy using a strut-adjusted volume implant (SAVI). For the nine patients included, dosimetric constraints for treatment were as follows: for the planning target volume for evaluation (PTV_Eval), the volume receiving 90, 150 and 200% of the prescribed dose (V90%,150%,200%) should be >90%, ≤50 cm3 and ≤20 cm3, respectively; the dose covering 1 cm3 (D1cc) of the organs at risk should be ≤110% of the prescribed dose; and the air volume should be ≤10% of PTV_Eval. Differences in V90%,150%,200%, D1cc and air volume ($\Delta V$ and $\Delta D$) as inter-fractional dosimetric variations and SAVI displacements were measured with pretreatment and planning computed tomography (CT) images. Inter-fractional dosimetric variations were analyzed for correlations with the SAVI displacements. The patients were divided into two groups based on the distance of the SAVI from the surface skin to assess the relationship between the insertion position of the SAVI and dosimetric parameters. The median ΔV90%,150%,200% for the PTV_Eval in all patients was -0.3%, 0.2 cm3 and 0.2 cm3, respectively. The median (range) ΔD1cc for the chest wall and surface skin was -0.8% (-18.9 to 9.4%) and 0.3% (-7.6 to 5.3%), respectively. SAVI displacement did not correlate with inter-fractional dosimetric variations. In conclusion, the dose constraints were satisfied in most cases. However, there were inter-fractional dosimetric changes due to SAVI displacement.

Analysis of key clinical features for achieving complete remission in stage III and IV non-small cell lung cancer patients.

BACKGROUND: Although development of immune checkpoint inhibitors and various molecular target agents has extended overall survival time (OS) in advanced non-small cell lung cancer (NSCLC), a complete cure remains rare. We aimed to identify features and treatment modalities of complete remission (CR) cases in stages III and IV NSCLC by analyzing long-term survivors whose OS exceeded 3 years. METHODS: From our hospital database, 1,699 patients, registered as lung cancer between 1st Mar 2004 and 30th Apr 2011, were retrospectively examined. Stage III or IV histologically or cytologically confirmed NSCLC patients with chemotherapy initiated during this period were enrolled. A Cox proportion hazards regression model was used. Data collection was closed on 13th Feb 2017. RESULTS: There were 164 stage III and 279 stage IV patients, including 37 (22.6%) and 51 (18.3%) long-term survivors and 12 (7.3%) and 5 (1.8%) CR patients, respectively. The long-term survivors were divided into three groups: 3 ≤ OS < 5 years, 5 years ≤ OS with tumor, and 5 years ≤ OS without tumor (CR). The median OS of these groups were 1,405, 2,238, and 2,876 days in stage III and 1,368, 2,503, and 2,643 days in stage IV, respectively. The mean chemotherapy cycle numbers were 16, 20, and 10 in stage III and 24, 25, and 5 in stage IV, respectively. In the stage III CR group, all patients received chemoradiation, all oligometastases were controlled by radiation, and none had brain metastases. Compared with non-CR patients, the stage IV CR patients had smaller primary tumors and fewer metastases, which were independent prognostic factors for OS among long-term survivors. The 80% stage IV CR patients received radiation or surgery for controlling primary tumors, and the surgery rate for oligometastases was high. Pathological findings in the stage IV CR patients revealed that numerous inflammatory cells existed around and inside resected lung and brain tumors, indicating strong immune response. CONCLUSIONS: Multiple line chemotherapies with primary and oligometastatic controls by surgery and/or radiation might achieve cure in certain advanced NSCLC. Cure strategies must be changed according to stage III or IV. This study was retrospectively registered on 16th Jun 2019 in UMIN Clinical Trials Registry (number UMIN000037078).

Questionnaire survey comparing surgery and stereotactic body radiotherapy for lung cancer: lessons from patients with experience of both modalities.

BACKGROUND: Currently, there is some controversy regarding indications for stereotactic body radiotherapy (SBRT) for lung cancer patients. We investigated the treatment preferences of patients with experience of both surgery and SBRT using a questionnaire survey. METHODS: Of lung cancer patients treated with SBRT between 2005 and 2017, we identified those who also previously underwent surgery for lung cancer. These patients were asked about their experiences of surgery and SBRT including perceived condition, distress, stress, convenience, adverse effects, and satisfaction during and after treatment. Participants were also asked about treatment decision-making for hypothetical scenarios. RESULTS: Of 653 lung cancer patients treated with SBRT, 149 also underwent surgery for lung cancer, 52 of whom participated in this questionnaire. The median age at the time of this survey was 76 years (range, 59-91 years). Significantly more participants had a favorable impression of SBRT during and after treatment (all question items; P<0.01). In terms of overall satisfaction, 27 patients preferred SBRT and three patients preferred surgery. In a hypothetical scenario (equivalent treatment outcomes) aged 70 years and faced with decision-making for first-time lung cancer treatment, significantly more patients selected SBRT (P<0.01): 38 patients selected SBRT. In a scenario with 20% better survivals for surgical resection, 14 patients selected SBRT, 12 selected surgery, and 26 were indecisive (P=0.47). In a scenario at age 80 years, significantly more patients selected SBRT (P<0.01). CONCLUSIONS: Most patients with experience of both surgery and SBRT for lung cancer prefer SBRT. This information would be helpful at treatment decision-making.

[Efficient Commissioning of the Radiotherapy Treatment Planning System with the Golden Beam Data].

Commissioning of a linear accelerator (Linac) and treatment planning systems (RTPs) for clinical use is complex and time-consuming, typically 3-4 months in total. However, based on clinical needs and economics, hospitals desire early clinical starts for patients, and various studies have been conducted for shortening the preparation period. One of the methods to shorten the period is using golden beam data (GBD). The purpose of this study was to shorten the commissioning period without reducing accuracy and to simplify commissioning works while improving safety. We conducted commissioning of the RTPs before installing the Linac using GBD, and carried out verification immediately after the acceptance test. We used TrueBeam STx (Varian Medical Systems) and Eclipse (ver. 13.7, Varian Medical Systems) for RTPs and anisotropic analysis algorithm (AAA) and AcurosXB (AXB) for calculation algorithms. The difference between GBD and the measured beam data was 0.0 ± 0.2% [percentage depth dose (PDDs) ] and -0.1 ± 0.2% (Profiles) with X-ray, and -1.2 ± 1.3% (PDDs) with electrons. The difference between the calculated dose and the measured dose was 0.1 ± 0.3% (AAA) and 0.0 ± 0.3% (AXB) under homogeneous conditions, and 0.7 ± 1.4% (AAA) and 0.6 ± 1.1% (AXB) under heterogeneous conditions. We took 43 days from the end of the acceptance test to the start of clinical use. We found that the preparation period for clinical use can be shortened without reducing the accuracy, by thinning out the number of measurement items using GBD.

Stereotactic body radiotherapy for patients with non-small-cell lung cancer using RapidArc delivery and a steep dose gradient: prescription of 60% isodose line of maximum dose fitting to the planning target volume.

We retrospectively investigated outcomes, including pulmonary toxicities, of stereotactic body radiation therapy using RapidArc and a risk-adapted 60% isodose plan for early-stage non-small-cell lung cancer patients. We evaluated patients staged as cT1a-2bN0M0 between 2011 and 2017 and treated with a total dose of 40-60 Gy in five fractions to the 60% isodose line of the maximum dose encompassing the planning target volume with curative intent. Comorbidities and age were rated using an age-adjusted Charlson comorbidity index (AACCI). Factors associated with overall survival (OS) were investigated. A total of 237 patients with 250 lesions were eligible. The median follow-up was 28.0 months. The local recurrence rate at 3 years was 0.8%; none of the patients developed isolated local recurrence. OS, deaths from lung cancer, and deaths from intercurrent disease at 3 years were 72.7%, 8.2% and 19.1%, respectively. On multivariate analysis for correlating factors with OS, AACCI and maximal standardized uptake value on [18F]-fluorodeoxyglucose positron emission tomography/computed tomography remained significant. Grade ≥3 toxicities were limited to radiation pneumonitis in six (2.4%) patients (Grade 3 in four patients and Grade 5 in two patients). Among those, three patients had idiopathic interstitial pneumonia. The total dose was unrelated to the incidence of Grade ≥3 radiation pneumonitis (P = 0.69). Using the 60% isodose prescription and RapidArc, maximal local control was achieved with acceptable toxicities. Although the OS may depend on patient background, dose escalation aiming at higher local control can be beneficial for medically inoperable patients.

Clarithromycin mitigates radiation pneumonitis in patients with lung cancer treated with stereotactic body radiotherapy.

BACKGROUND: Radiation pneumonitis is a critical pulmonary toxicity after irradiation of the lung. Macrolides including clarithromycin (CAM) are antibiotics. They also have immunomodulatory properties and are used to treat respiratory inflammatory diseases. Radiation pneumonitis has similar pathology to them. Adverse reactions to macrolides are few and self-limited. We thus administered CAM to patients with high-risk factors for radiation pneumonitis, and retrospectively investigated whether CAM mitigated radiation pneumonitis following stereotactic body radiotherapy (SBRT). METHODS: Among consecutive patients treated with SBRT, we retrospectively examined lung cancer patients treated with a total dose of 40-60 Gy in 5-10 fractions and followed ≥6 months. Since January 2014, CAM has been administered in patients with pretreatment predictable radiation pneumonitis high-risk factors, including idiopathic interstitial pneumonias (IIPs), and elevated Krebs von den Lungen-6 (KL-6) and/or surfactant protein D (SP-D), and in patients developing early onset radiation pneumonitis. RESULTS: Five hundred and eighty eligible patients were identified and divided into 445 patients during the non-CAM-administration era (non-CAM-era) (before December 2013) and 136 patients during the CAM-administration era (CAM-era) (after January 2014). Median follow-up durations were 38.0 and 13.9 months, respectively. The rates of radiation pneumonitis ≥ grade 2 and ≥ grade 3 were significantly lower in CAM-era (grade ≥2, 16% vs. 9.6%, P=0.047; grade ≥3, 3.8% vs. 0.73%, P=0.037). For patients with the pretreatment predictable high-risk factors, the rate of radiation pneumonitis ≥ grade 3 was significantly lower, and that of grade ≥2 had a lower tendency (grade ≥3, 7.2% vs. 0%, P=0.011; grade ≥2, 21% vs. 9.6%, P=0.061). For patients developing early onset radiation pneumonitis, the rate of radiation pneumonitis ≥ grade 3 was also significantly lower (23% vs. 0%, P<0.05). Multivariate analysis revealed that dose-volumetric factor, the pretreatment predictable high-risk factors and non-CAM-administration era were significantly associated with or trended toward radiation pneumonitis ≥ grade 2 and ≥ grade 3. CONCLUSIONS: CAM mitigated radiation pneumonitis following SBRT. The efficacy of CAM should be confirmed in prospective studies.