Feasibility study of deep learning-based markerless real-time lung tumor tracking with orthogonal X-ray projection images.

PURPOSE: The feasibility of a deep learning-based markerless real-time tumor tracking (RTTT) method was retrospectively studied with orthogonal kV X-ray images and clinical tracking records acquired during lung cancer treatment. METHODS: Ten patients with lung cancer treated with marker-implanted RTTT were included. The prescription dose was 50 Gy in four fractions, using seven- to nine-port non-coplanar static beams. This corresponds to 14-18 X-ray tube angles for an orthogonal X-ray imaging system rotating with the gantry. All patients underwent 10 respiratory phases four-dimensional computed tomography. After a data augmentation approach, for each X-ray tube angle of a patient, 2250 digitally reconstructed radiograph (DRR) images with gross tumor volume (GTV) contour labeled were obtained. These images were adopted to train the patient and X-ray tube angle-specific GTV contour prediction model. During the testing, the model trained with DRR images predicted GTV contour on X-ray projection images acquired during treatment. The predicted three-dimensional (3D) positions of the GTV were calculated based on the centroids of the contours in the orthogonal images. The 3D positions of GTV determined by the marker-implanted RTTT during the treatment were considered as the ground truth. The 3D deviations between the prediction and the ground truth were calculated to evaluate the performance of the model. RESULTS: The median GTV volume and motion range were 7.42 (range, 1.18-25.74) cm3 and 22 (range, 11-28) mm, respectively. In total, 8993 3D position comparisons were included. The mean calculation time was 85 ms per image. The overall median value of the 3D deviation was 2.27 (interquartile range: 1.66-2.95) mm. The probability of the 3D deviation smaller than 5 mm was 93.6%. CONCLUSIONS: The evaluation results and calculation efficiency show the proposed deep learning-based markerless RTTT method may be feasible for patients with lung cancer.

Development of a prediction model for target positioning by using diaphragm waveforms extracted from CBCT projection images.

PURPOSE: To develop a prediction model (PM) for target positioning using diaphragm waveforms extracted from CBCT projection images. METHODS: Nineteen patients with lung cancer underwent orthogonal rotational kV x-ray imaging lasting 70 s. IR markers placed on their abdominal surfaces and an implanted gold marker located nearest to the tumor were considered as external surrogates and the target, respectively. Four different types of regression-based PM were trained using surrogate motions and target positions for the first 60 s, as follows: Scenario A: Based on the clinical scenario, 3D target positions extracted from projection images were used as they were (PMCL ). Scenario B: The short-arc 4D-CBCT waveform exhibiting eight target positions was obtained by averaging the target positions in Scenario A. The waveform was repeated for 60 s (W4D-CBCT ) by adapting to the respiratory phase of the external surrogate. W4D-CBCT was used as the target positions (PM4D-CBCT ). Scenario C: The Amsterdam Shroud (AS) signal, which depicted the diaphragm motion in the superior-inferior direction was extracted from the orthogonal projection images. The amplitude and phase of W4D-CBCT were corrected based on the AS signal. The AS-corrected W4D-CBCT was used as the target positions (PMAS-4D-CBCT ). Scenario D: The AS signal was extracted from single projection images. Other processes were the same as in Scenario C. The prediction errors were calculated for the remaining 10 s. RESULTS: The 3D prediction error within 3 mm was 77.3% for PM4D-CBCT , which was 12.8% lower than that for PMCL . Using the diaphragm waveforms, the percentage of errors within 3 mm improved by approximately 7% to 84.0%-85.3% for PMAS-4D-CBCT in Scenarios C and D, respectively. Statistically significant differences were observed between the prediction errors of PM4D-CBCT and PMAS-4D-CBCT . CONCLUSION: PMAS-4D-CBCT outperformed PM4D-CBCT , proving the efficacy of the AS signal-based correction. PMAS-4D-CBCT would make it possible to predict target positions from 4D-CBCT images without gold markers.

Efficacy of local salvage therapy for recurrent uterine cervical cancer after definitive radiotherapy.

BACKGROUND: The prognosis of patients with recurrence of uterine cervical cancer after definitive radiotherapy and the efficacy of local salvage therapy for recurrence were evaluated. METHODS: We retrospectively reviewed 110 patients who were treated with definitive radiotherapy/chemoradiotherapy for uterine cervical cancer between 2008 and 2017 at our institution. Local salvage therapy was defined as any surgery or radiotherapy described in the medical record as intended for local control or cure. RESULTS: We identified 25 patients who developed recurrence after definitive radiotherapy/chemoradiotherapy. The median follow-up time post-recurrence was 18.9 months. Thirteen patients (52%) reported recurrence in the isolated extra-pelvic lymph node (EPLN). The 2-year overall survival after first recurrence (OSr) for patients with isolated EPLN recurrence was 83.1%, compared to that of 31.2% for patients with other patterns of recurrence (p < 0.001). The 2-year OSr for patients who underwent local salvage therapy was 75.2%, whereas that for patients who did not undergo therapy was 41.6% (p = 0.04). Among patients who had recurrence in the isolated EPLN and received local salvage therapy, 20% of the patients reported recurrence in visceral and/or bone metastases after local salvage therapy, and 50% of the patients experienced another EPLN recurrence, which was salvaged with repeating local therapy. CONCLUSIONS: Patients with uterine cervical cancer with isolated EPLN recurrence had favorable prognoses. The indications of local salvage therapy should be considered, especially for patients with isolated EPLN recurrence.

Impact of histology on patterns of failure and clinical outcomes in patients treated with definitive chemoradiotherapy for locally advanced non-small cell lung cancer.

BACKGROUND: Chemoradiotherapy is the standard treatment for locally advanced non-small cell lung cancer. Unlike metastatic disease, histological differences are usually not considered while planning chemoradiotherapy. This study aimed to compare clinical outcomes and relapse patterns between squamous cell carcinomas and adenocarcinomas, and investigated possible histology-specific approaches for chemoradiotherapy in locally advanced non-small cell lung cancer. METHODS: We retrospectively analyzed the outcomes and relapse patterns in patients who received definitive chemoradiotherapy for locally advanced non-small cell lung cancer in Katsura hospital between 2003 and 2012. RESULTS: A total of 68 and 33 patients with squamous cell carcinomas and adenocarcinomas, respectively, were enrolled. Patients with adenocarcinoma had less advanced T stages, and a larger proportion of female patients. Other factors were not different between the two groups. The median follow-up duration in all patients and survivors was 21.3 months and 91.4 months, respectively. Median survival and relapse-free survival were not significantly different between the two groups. In contrast, the failure patterns and incidences of distant failure were significantly different. Patients with squamous cell carcinomas had predominantly locoregional disease features and a shorter duration from relapse to death compared to patients with adenocarcinoma. CONCLUSION: Failure pattern was significantly different between the two histologies. Among relapsed patients, the prognosis was poorer in those with squamous cell carcinomas than those with adenocarcinomas. Further studies, to evaluate histology-specific approaches in chemoradiotherapy, are warranted.

Validation of the clinical applicability of knowledge-based planning models in single-isocenter volumetric-modulated arc therapy for multiple brain metastases.

PURPOSE: To validate the clinical applicability of knowledge-based (KB) planning in single-isocenter volumetric-modulated arc therapy (VMAT) for multiple brain metastases using the k-fold cross-validation (CV) method. METHODS: This study comprised 60 consecutive patients with multiple brain metastases treated with single-isocenter VMAT (28 Gy in five fractions). The patients were divided randomly into five groups (Groups 1-5). The data of Groups 1-4 were used as the training and validation dataset and those of Group 5 were used as the testing dataset. Four KB models were created from three of the training and validation datasets and then applied to the remaining Groups as the fourfold CV phase. As the testing phase, the final KB model was applied to Group 5 and the dose distributions were calculated with a single optimization process. The dose-volume indices (DVIs), modified Ian Paddick Conformity Index (mIPCI), modulation complexity scores for VMAT plans (MCSv), and the total number of monitor units (MUs) of the final KB plan were compared to those of the clinical plan (CL) using a paired Wilcoxon signed-rank test. RESULTS: In the fourfold CV phase, no significant differences were observed in the DVIs among the four KB plans (KBPs). In the testing phase, the final KB plan was statistically equivalent to the CL, except for planning target volumes (PTVs) D2% and D50% . The differences between the CL and KBP in terms of the PTV D99.5% , normal brain, and Dmax to all organs at risk (OARs) were not significant. The KBP achieved a lower total number of MUs and higher MCSv than the CL with no significant difference. CONCLUSIONS: We demonstrated that a KB model in a single-isocenter VMAT for multiple brain metastases was equivalent in dose distribution, MCSv, and total number of MUs to a CL with a single optimization.

Independent calculation-based verification of volumetric-modulated arc therapy-stereotactic body radiotherapy plans for lung cancer.

This study aimed to investigate the feasibility of independent calculation-based verification of volumetric-modulated arc therapy (VMAT)-stereotactic body radiotherapy (SBRT) for patients with lung cancer using a secondary treatment planning system (sTPS). In all, 50 patients with lung cancer who underwent VMAT-SBRT between April 2018 and May 2019 were included in this study. VMAT-SBRT plans were devised using the Collapsed-Cone Convolution in RayStation (primary TPS: pTPS). DICOM files were transferred to Eclipse software (sTPS), which utilized the Eclipse software, and the dose distribution was then recalculated using Acuros XB. For the verification of dose distribution in homogeneous phantoms, the differences among pTPS, sTPS, and measurements were evaluated using passing rates of a dose difference of 5% (DD5%) and gamma index of 3%/2 mm (γ3%/2 mm). The ArcCHECK cylindrical diode array was used for measurements. For independent verification of dose-volume parameters per the patient's geometry, dose-volume indices for the planning target volume (PTV) including D95% and the isocenter dose were evaluated. The mean differences (± standard deviations) between the pTPS and sTPS were then calculated. The gamma passing rates of DD5% and γ3%/2 mm criteria were 99.2 ± 2.4% and 98.6 ± 3.2% for pTPS vs. sTPS, 92.9 ± 4.0% and 94.1 ± 3.3% for pTPS vs. measurement, and 93.0 ± 4.4% and 94.3 ± 4.1% for sTPS vs. measurement, respectively. The differences between pTPS and sTPS for the PTVs of D95% and the isocenter dose were -3.1 ± 2.0% and -2.3 ± 1.8%, respectively. Our investigation of VMAT-SBRT plans for lung cancer revealed that independent calculation-based verification is a time-efficient method for patient-specific quality assurance.

Final report of survival and late toxicities in the Phase I study of stereotactic body radiation therapy for peripheral T2N0M0 non-small cell lung cancer (JCOG0702).

PURPOSE: A dose escalation study to determine the recommended dose with stereotactic body radiation therapy (SBRT) for peripheral T2N0M0 non-small cell carcinomas (JCOG0702) was conducted. The purpose of this paper is to report the survival and the late toxicities of JCOG0702. MATERIALS AND METHODS: The continual reassessment method was used to determine the dose level that patients should be assigned to and to estimate the maximum tolerated dose. The starting dose was 40 Gy in four fractions at D95 of PTV. RESULTS: Twenty-eight patients were enrolled. Ten patients were treated with 40 Gy at D95 of PTV, four patients with 45 Gy, eight patients with 50 Gy, one patient with 55 Gy and five patients with 60 Gy. Ten patients were alive at the last follow-up. Overall survival (OS) for all patients was 67.9% (95% CI 47.3-81.8%) at 3 years and 40.8% (95% CI 22.4-58.5%) at 5 years. No Grade 3 or higher toxicity was observed after 181 days from the beginning of the SBRT. Compared to the toxicities up to 180 days, chest wall related toxicities were more frequent after 181 days. CONCLUSIONS: The 5-year OS of 40.8% indicates the possibility that SBRT for peripheral T2N0M0 non-small cell lung cancer is superior to conventional radiotherapy. The effect of the SBRT dose escalation on OS is unclear and further studies are warranted.

Long-term outcomes of intensity-modulated radiotherapy following extra-pleural pneumonectomy for malignant pleural mesothelioma.

BACKGROUND: The purpose was to evaluate safety and efficacy of intensity-modulated radiotherapy (IMRT) following extra-pleural pneumonectomy (EPP) for malignant pleural mesothelioma (MPM). MATERIAL AND METHODS: Patients with MPM of clinical stage I-III, which were macroscopic completely resected with EPP were eligible for this prospective study. The ipsilateral hemithorax was irradiated with a prescribed dose of 50.4 Gy. When the high-risk surgical margins or FDG-avid regions were identified, simultaneous integrated boost (SIB) with 56.0 Gy or 61.6 Gy was applied. RESULTS: Twenty-one patients were enrolled. SIB was applied to five patients. The planned IMRT fractions were completed in all, but four patients who suffered from severe fatigue or radiation pneumonitis. With a potential median follow-up of 6.3 years, overall survival was 37.5% at 3 years since the IMRT. The median survival time was 17.5 and 27.0 months since the IMRT and the initial treatment, respectively. Three patients have survived for more than 5 years. Distant metastasis was observed in 15 patients. Local recurrence was also observed in 2 of the 15 patients. Acute toxicities of Grade 3 or worse were observed in 15 patients, including 9 with hematological, 3 with pneumonitis and 6 with fatigue, nausea or vomiting. Five patients developed Grade 3 or worse late toxicities associated with IMRT, consisting of one with persistent Grade 4 thrombocytopenia, one with brain infarction and congestive liver dysfunction, and three with elevation of serum transaminase or biliary enzyme. No Grade 5 toxicity was observed. Patients with N2 showed significantly worse survival than those with N0-1 (18.2% vs. 60.0% at 3 years, p = .014). CONCLUSION: IMRT following EPP achieved excellent local control for MPM, that might lead to the long-term survival in selected patients. However, treatment burden including acute and late toxicities should be considered in this treatment approach.

Phase I study of stereotactic body radiation therapy for centrally located stage IA non-small cell lung cancer (JROSG10-1).

BACKGROUND: To investigate the maximum tolerated dose (MTD) and recommended dose (RD) of stereotactic body radiation therapy (SBRT) for centrally located stage IA non-small cell lung cancer (NSCLC). METHODS: Five dose levels, ranging from of 52 to 68 Gy in eight fractions, were determined; the treatment protocol began at 60 Gy (level 3). Each dose level included 10 patients. Levels 1-2 were indicated if more than four patients exhibited dose-limiting toxicity (DLT), which was defined as an occurrence of a grade 3 (or worse) adverse effect within 12 months after SBRT initiation. MTD was defined as the lowest dose level at which more than four patients exhibited DLT. RESULTS: Ten patients were enrolled in the level 3 study. One patient was considered unsuitable because of severe emphysema. Therefore, nine patients were evaluated and no patient exhibited DLT. The level 3 results indicated that we should proceed to level 4 (64 Gy). However, due to the difficulty involved in meeting the dose constraints, further dose escalation was not feasible and the MTD was found to be 60 Gy. CONCLUSIONS: The RD of SBRT for centrally located stage IA NSCLC was 60 Gy in eight fractions.

Dosimetric evaluation of the Acuros XB algorithm for a 4 MV photon beam in head and neck intensity-modulated radiation therapy.

In this study, we assessed the differences in the dose distribution of a 4 MV photon beam among different calculation algorithms: the Acuros XB (AXB) algorithm, the analytic anisotropic algorithm (AAA), and the pencil beam convolution (PBC) algorithm (ver. 11.0.31), in phantoms and in clinical intensity-modulated radiation therapy (IMRT) plans. Homogeneous and heterogeneous, including middle-, low-, and high-density, phantoms were combined to assess the percentage depth dose and lateral dose profiles among AXB, AAA, and PBC. For the phantom containing the low-density area, AXB was in agreement with measurement within 0.5%, while the greatest differences between the AAA and PBC calculations and measurement were 2.7% and 3.6%, respectively. AXB showed agreement with measurement within 2.5% at the high-density area, while AAA and PBC overestimated the dose by more than 4.5% and 4.0%, respectively. Furthermore, 15 IMRT plans, calculated using AXB, for oropharyngeal, hypopharyngeal, and laryngeal carcinomas were analyzed. The dose prescription was 70 Gy to 50% of the planning target volume (PTV70). Subsequently, each plan was recalculated using AAA and PBC while maintaining the AXB-calculated monitor units, leaf motion, and beam arrangement. Additionally, nine hypopharyngeal and laryngeal cancer patients were analyzed in terms of PTV70 for cartilaginous structures (PTV(70_cartilage)). The doses covering 50% to PTV70 calculated by AAA and PBC were 2.1% ± 1.0% and 3.7% ± 0.8% significantly higher than those using AXB, respectively (p < 0.01). The increases in doses to PTV(70_cartilage) calculated by AAA and PBC relative to AXB were 3.9% and 5.3% on average, respectively, and were relatively greater than those in the entire PTV70. AXB was found to be in better agreement with measurement in phantoms in heterogeneous areas for the 4 MV photon beam. Considering AXB as the standard, AAA and PBC overestimated the IMRT dose for head and neck cancer. The dosimetric differences should not be ignored, particularly with cartilaginous structures in PTV.

Baseline correction of a correlation model for improving the prediction accuracy of infrared marker-based dynamic tumor tracking.

We previously found that the baseline drift of external and internal respiratory motion reduced the prediction accuracy of infrared (IR) marker-based dynamic tumor tracking irradiation (IR Tracking) using the Vero4DRT system. Here, we proposed a baseline correction method, applied immediately before beam delivery, to improve the prediction accuracy of IR Tracking. To perform IR Tracking, a four-dimensional (4D) model was constructed at the beginning of treatment to correlate the internal and external respiratory signals, and the model was expressed using a quadratic function involving the IR marker position (x) and its velocity (v), namely function F(x,v). First, the first 4D model, F1st(x,v), was adjusted by the baseline drift of IR markers (BDIR) along the x-axis, as function F'(x,v). Next, BDdetect, that defined as the difference between the target positions indicated by the implanted fiducial markers (Pdetect) and the predicted target positions with F'(x,v) (Ppredict) was determined using orthogonal kV X-ray images at the peaks of the Pdetect of the end-inhale and end-exhale phases for 10 s just before irradiation. F'(x,v) was corrected with BDdetect to compensate for the residual error. The final corrected 4D model was expressed as Fcor(x,v) = F1st{(x-BDIR),v}-BDdetect. We retrospectively applied this function to 53 paired log files of the 4D model for 12 lung cancer patients who underwent IR Tracking. The 95th percentile of the absolute differences between Pdetect and Ppredict (|Ep|) was compared between F1st(x,v) and Fcor(x,v). The median 95th percentile of |Ep| (units: mm) was 1.0, 1.7, and 3.5 for F1st(x,v), and 0.6, 1.1, and 2.1 for Fcor(x,v) in the left-right, anterior-posterior, and superior-inferior directions, respectively. Over all treatment sessions, the 95th percentile of |Ep| peaked at 3.2 mm using Fcor(x,v) compared with 8.4 mm using F1st(x,v). Our proposed method improved the prediction accuracy of IR Tracking by correcting the baseline drift immediately before irradiation.

Radiotherapy for patients with isolated local recurrence of primary resected pancreatic cancer. Prolonged disease-free interval associated with favorable prognosis.

BACKGROUND AND PURPOSE: To evaluate the treatment outcomes of radiotherapy and prognostic factors for recurrent pancreatic cancer. PATIENTS AND METHODS: The study comprised 30 patients who developed a locoregional recurrence of primarily resected pancreatic cancer and received radiotherapy between 2000 and 2013 with a median dose of 54 Gy (range, 39-60 Gy). Concurrent chemotherapy included gemcitabine for 18 patients and S-1 for seven patients. The treatment outcomes and prognostic factors were retrospectively analyzed. RESULTS: The median follow-up after radiotherapy was 14.6 months. The 1-year overall survival, local control, and progression-free survival rates were 69%, 67%, and 32%, respectively. The median overall survival and progression-free survival rates were 15.9 and 6.9 months, respectively. Tumor marker reduction and ≥ 50% reduction were observed in 18 and two patients, respectively. Of the seven patients who exhibited pain symptoms, four and two patients were partly and completely relieved, respectively. Late grade 3 ileus and gastroduodenal bleeding were observed in one patient each. Among the clinicopathological factors evaluated, only a disease-free interval of greater than 18.9 months exhibited a significant association with improved overall survival (p = 0.017). CONCLUSIONS: Radiotherapy for isolated locally recurrent pancreatic cancer resulted in encouraging local control, overall survival, and palliative effects with mild toxicity, particularly in patients with a prolonged disease-free interval. This treatment strategy should be prospectively evaluated.

Safety and effectiveness of stereotactic body radiotherapy for a clinically diagnosed primary stage I lung cancer without pathological confirmation.

BACKGROUND: Pathological diagnosis fails in some pulmonary tumors, although they may be highly suspected to be primary lung cancer. We studied the outcome of stereotactic body radiotherapy for a clinically diagnosed primary stage I lung cancer without pathological confirmation. METHODS: The current study included 37 patients (39 lesions) treated with stereotactic body radiotherapy who were clinically diagnosed with primary stage I lung cancer between August 1998 and April 2009 at our hospital. Pulmonary tumors were highly suspected to be malignant from physical and imaging examinations. Biopsies were performed for 62 % of patients, although malignancy was not pathologically confirmed. In the other 38 % of patients, a biopsy was not feasible. Median age of the patients was 77 years. Median tumor diameter was 20 mm. A total median dose of 48 Gy was prescribed to the isocenter in four fractions. Median follow-up period was 39 months. RESULTS: The 3-year overall survival, local control, and regional-distant control were 74.2, 94.0, and 68.6 %, respectively. In patients with tumors ≤20 mm, overall survival and regional-distant control were significantly higher than in patients with tumors >20 mm (p ≤ 0.001), whereas no significant difference was observed regarding local control. No grade 3-5 adverse events possibly, probably, or definitely related to the treatment were observed. CONCLUSIONS: Stereotactic body radiotherapy is safe and effective for a clinically diagnosed primary stage I lung cancer when pathological diagnosis is difficult even with repeat biopsies, or a biopsy is not feasible for reasons of the patient's health condition or wishes.

Dosimetric impact of gold markers implanted closely to lung tumors: a Monte Carlo simulation.

We are developing an innovative dynamic tumor tracking irradiation technique using gold markers implanted around a tumor as a surrogate signal, a real-time marker detection system, and a gimbaled X-ray head in the Vero4DRT. The gold markers implanted in a normal organ will produce uncertainty in the dose calculation during treatment planning because the photon mass attenuation coefficient of a gold marker is much larger than that of normal tissue. The purpose of this study was to simulate the dose variation near the gold markers in a lung irradiated by a photon beam using the Monte Carlo method. First, the single-beam and the opposing-beam geometries were simulated using both water and lung phantoms. Subsequently, the relative dose profiles were calculated using a stereotactic body radiotherapy (SBRT) treatment plan for a lung cancer patient having gold markers along the anterior-posterior (AP) and right-left (RL) directions. For the single beam, the dose at the gold marker-phantom interface laterally along the perpendicular to the beam axis increased by a factor of 1.35 in the water phantom and 1.58 in the lung phantom, respectively. Furthermore, the entrance dose at the interface along the beam axis increased by a factor of 1.63 in the water phantom and 1.91 in the lung phantom, while the exit dose increased by a factor of 1.00 in the water phantom and 1.12 in the lung phantom, respectively. On the other hand, both dose escalations and dose de-escalations were canceled by each beam for opposing portal beams with the same beam weight. For SBRT patient data, the dose at the gold marker edge located in the tumor increased by a factor of 1.30 in both AP and RL directions. In clinical cases, dose escalations were observed at the small area where the distance between a gold marker and the lung tumor was ≤ 5 mm, and it would be clinically negligible in multibeam treatments, although further investigation may be required.

Dosimetric verification of four dose calculation algorithms for spine stereotactic body radiotherapy.

The applications of Type B [anisotropic analytical algorithm (AAA) and collapsed cone (CC)] and Type C [Acuros XB (AXB) and photon Monte Carlo (PMC)] dose calculation algorithms in spine stereotactic body radiotherapy (SBRT) were evaluated. Water- and bone-equivalent phantoms were combined to evaluate the percentage depth dose and dose profile. Subsequently, 48 consecutive patients with clinical spine SBRT plans were evaluated. All treatment plans were created using AXB in Eclipse. The prescription dose was 24 Gy in two fractions at a 10 MV FFF on TrueBeam. The doses were then recalculated with AAA, CC and PMC while maintaining the AXB-calculated monitor units and beam arrangement. The dose index values obtained using the four dose calculation algorithms were then compared. The AXB and PMC dose distributions agreed with the bone-equivalent phantom measurements (within ±2.0%); the AAA and CC values were higher than those in the bone-equivalent phantom region. For the spine SBRT plans, PMC, AAA and CC were overestimated compared with AXB in terms of the near minimum and maximum doses of the target and organ at risk, respectively; the mean dose difference was within 4.2%, which is equivalent with within 1 Gy. The phantom study showed that the results from AXB and PMC agreed with the measurements within ±2.0%. However, the mean dose difference ranged from 0.5 to 1 Gy in the spine SBRT planning study when the dose calculation algorithms changed. Users should incorporate a clinical introduction that includes an awareness of these differences.

Validation of the Lung-Mol Graded Prognostic Assessment (GPA) System for the Prognosis of Patients Receiving Radiotherapy for Brain Metastasis From Non-small Cell Lung Cancer.

PURPOSE: The Lung-mol graded prognostic assessment (GPA) system predicts the prognosis of patients with brain metastases (BM) from non-small cell lung cancer (NSCLC) separately for adenocarcinoma and non-adenocarcinoma. This study aimed to validate the Lung-molGPA system using a cohort of patients in our institution who received radiotherapy for BM. MATERIALS AND METHODS: Three hundred and thirty-nine patients with NSCLC who received their first course of radiotherapy for BM were included in the analysis. Among them, 65 received their second course of radiotherapy for BM. Data on sex, age, Karnofsky performance status (KPS), extracranial metastases (ECM), number of BM, histological type, and gene mutations were collected according to the Lung-molGPA system. We examined the validity of the scores assigned to the factors included in the Lung-molGPA system, separately for adenocarcinoma and non-adenocarcinoma. In addition, we validated the Lung-molGPA system to predict survival during both the first and second courses of radiotherapy. RESULTS: The factors in the Lung-molGPA were significantly associated with survival, except for age in non-adenocarcinoma with marginal significance. Regarding discrimination ability, the C-indices were 0.65 and 0.69 for adenocarcinoma and non-adenocarcinoma, respectively, in the first course of radiotherapy for BM, while those in the second course were 0.62 and 0.74, respectively. Survival prediction by Lung-molGPA was almost consistent with actual survival in the first course of radiotherapy, except for the score of 0-1.0 in both histologies and 2.5-3.0 in non-adenocarcinoma. In the second course of radiotherapy, median survival could be predicted for some patients with adenocarcinoma. CONCLUSIONS: Our study confirms the validity of Lung-molGPA for the estimation of median survival based on patient characteristics at the time of initiation of radiotherapy for patients in the first course of radiotherapy and shows that it may be applicable to patients with adenocarcinoma in the second course of radiotherapy.

Unifying gamma passing rates in patient-specific QA for VMAT lung cancer treatment based on data assimilation.

This study aimed to identify systematic errors in measurement-, calculation-, and prediction-based patient-specific quality assurance (PSQA) methods for volumetric modulated arc therapy (VMAT) on lung cancer and to standardize the gamma passing rate (GPR) by considering systematic errors during data assimilation. This study included 150 patients with lung cancer who underwent VMAT. VMAT plans were generated using a collapsed-cone algorithm. For measurement-based PSQA, ArcCHECK was employed. For calculation-based PSQA, Acuros XB was used to recalculate the plans. In prediction-based PSQA, GPR was forecasted using a previously developed GPR prediction model. The representative GPR value was estimated using the least-squares method from the three PSQA methods for each original plan. The unified GPR was computed by adjusting the original GPR to account for systematic errors. The range of limits of agreement (LoA) were assessed for the original and unified GPRs based on the representative GPR using Bland-Altman plots. For GPR (3%/2 mm), original GPRs were 94.4 ± 3.5%, 98.6 ± 2.2% and 93.3 ± 3.4% for measurement-, calculation-, and prediction-based PSQA methods and the representative GPR was 95.5 ± 2.0%. Unified GPRs were 95.3 ± 2.8%, 95.4 ± 3.5% and 95.4 ± 3.1% for measurement-, calculation-, and prediction-based PSQA methods, respectively. The range of LoA decreased from 12.8% for the original GPR to 9.5% for the unified GPR across all three PSQA methods. The study evaluated unified GPRs that corrected for systematic errors. Proposing unified criteria for PSQA can enhance safety regardless of the methods used.

Cone-beam computed tomography-guided online adaptive radiotherapy for pharyngeal cancer with whole neck irradiation: dose-volume histogram analysis between adapted and scheduled plans.

The present study aimed to evaluate whether an adapted plan with Ethos™ could be used for pharyngeal cancer. Ten patients with pharyngeal cancer who underwent chemoradiotherapy with available daily cone-beam computed tomography (CBCT) data were included. Simulated treatments were generated on the Ethos™ treatment emulator using CBCTs every four to five fractions for two plans: adapted and scheduled. The simulated treatments were divided into three groups: early (first-second week), middle (third-fourth week), and late (fifth-seventh week) periods. Dose-volume histogram parameters were compared for each period between the adapted and scheduled plans in terms of the planning target volume (PTV) (D98%, D95%, D50% and D2%), spinal cord (Dmax and D1cc), brainstem (Dmax) and ipsilateral and contralateral parotid glands (Dmedian and Dmean). The PTV D98%, D95% and D2% of the adapted plan were significantly higher than those of the scheduled plans in all periods, except for D98% in the late period. The adapted plan significantly reduced the spinal cord Dmax and D1cc compared with the scheduled plan in all periods. Ipsilateral and contralateral parotid glands Dmean of the adapted plan were lower than those of scheduled plan in the late period. In conclusion, the present study revealed that the adapted plans could maintain PTV coverage while reducing the doses to organs at risk in each period compared with scheduled plans.

Population-based asymmetric margins for moving targets in real-time tumor tracking.

BACKGROUND: Both geometric and dosimetric components are commonly considered when determining the margin for planning target volume (PTV). As dose distribution is shaped by controlling beam aperture in peripheral dose prescription and dose-escalated simultaneously integrated boost techniques, adjusting the margin by incorporating the variable dosimetric component into the PTV margin is inappropriate; therefore, geometric components should be accurately estimated for margin calculations. PURPOSE: We introduced an asymmetric margin-calculation theory using the guide to the expression of uncertainty in measurement (GUM) and intra-fractional motion. The margins in fiducial marker-based real-time tumor tracking (RTTT) for lung, liver, and pancreatic cancers were calculated and were then evaluated using Monte Carlo (MC) simulations. METHODS: A total of 74 705, 73 235, and 164 968 sets of intra- and inter-fractional positional data were analyzed for 48 lung, 48 liver, and 25 pancreatic cancer patients, respectively, in RTTT clinical trials. The 2.5th and 97.5th percentiles of the positional error were considered representative values of each fraction of the disease site. The population-based statistics of the probability distributions of these representative positional errors (PD-RPEs) were calculated in six directions. A margin covering 95% of the population was calculated using the proposed formula. The content rate in which the clinical target volume (CTV) was included in the PTV was calculated through MC simulations using the PD-RPEs. RESULTS: The margins required for RTTT were at most 6.2, 4.6, and 3.9 mm for lung, liver, and pancreatic cancer, respectively. MC simulations revealed that the median content rates using the proposed margins satisfied 95% for lung and liver cancers and 93% for pancreatic cancer, closer to the expected rates than the margins according to van Herk's formula. CONCLUSIONS: Our proposed formula based on the GUM and motion probability distributions (MPD) accurately calculated the practical margin size for fiducial marker-based RTTT. This was verified through MC simulations.

Clinical outcomes of scalp or face angiosarcoma treatment with intensity-modulated radiotherapy: a multicenter study.

Combined modality therapy, including radiotherapy (RT), is a common treatment for scalp or face angiosarcoma. Although intensity-modulated radiotherapy (IMRT) can deliver homogeneous doses to the scalp or face, clinical data are limited. This multicenter study aimed to evaluate scalp or face angiosarcoma treated with definitive or post-operative IMRT. We retrospectively analyzed data from patients who received IMRT for scalp or face angiosarcoma at three institutions between January 2015 and March 2020. Local control (LC) rate, overall survival (OS), progression-free survival (PFS), recurrence patterns and toxicity were evaluated. Fifteen patients underwent IMRT during the study period. Definitive RT was performed on 10 patients and post-operative RT was performed on 5 patients. The 1-year LC rate was 85.7% (95% confidence interval [CI], 53.9-96.2%). The 1-year OS and PFS rates were 66.7% (95% CI, 37.5-84.6%) and 53.3% (95% CI, 26.3%-74.4%), respectively. Univariate analysis revealed that a clinical target volume over 500 cm3 was associated with poor LC. Distant metastasis was the most common recurrence pattern. All patients experienced Grade 2 or 3 radiation dermatitis, and five patients experienced grade ≥ 3 skin ulceration. One patient who underwent maintenance therapy with pazopanib developed Grade 5 skin ulceration. Fisher's exact test showed that post-operative RT was significantly associated with an increased risk of skin ulceration of grade ≥ 3. These results demonstrate that IMRT is a feasible and effective treatment for scalp or face angiosarcoma, although skin ulceration of grade ≥ 3 is a common adverse event in patients who receive post-operative RT.