Robust and optimal dose distribution for brain metastases with robotic radiosurgery system: recipe for an inflection point.

Purpose.This study aims to establish a robust dose prescription methodology in stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT) for brain metastases, considering geometrical uncertainty and minimising dose exposure to the surrounding normal brain tissue.Methods and Materials.Treatment plans employing 40%-90% isodose lines (IDL) at 10% IDL intervals were created for variously sized brain metastases. The plans were constructed to deliver 21 Gy in SRS. Robustness of each plan was analysed using parameters such as the near minimum dose to the tumour, the near maximum dose to the normal brain, and the volume of normal brain irradiated above 14 Gy.Results.Plans prescribed at 60% IDL demonstrated the least variation in the near minimum dose to the tumour and the near maximum dose to the normal brain under conditions of minimal geometrical uncertainty relative to tumour radius. When the IDL-percentage prescription was below 60%, geometrical uncertainties led to increases in these doses. Conversely, they decreased with IDL-percentage prescriptions above 60%. The volume of normal brain irradiated above 14 Gy was lowest at 60% IDL, regardless of geometrical uncertainty.Conclusions.To enhance robustness against geometrical uncertainty and to better spare healthy brain tissue, a 60% IDL prescription is recommended in SRS and SRT for brain metastases using a robotic radiosurgery system.

Single isocenter dynamic conformal arcs-based radiosurgery for brain metastases: Dosimetric comparison with Cyberknife and clinical investigation.

Purpose: To compare the dosimetric quality of automatic multiple brain metastases planning (MBM) with that of Cyberknife (CK) based on the clinical tumor condition, such as the tumor number, size, and location. Methods: 76 treatment plans for 46 patients treated with CK were recalculated with the MBM treatment planning system. Conformity index (CI), homogeneity index (HI), gradient index (GI), lesion underdosage volume factor (LUF), healthy tissue overdose volume factor (HTOF), geometric conformity index (g) and mean dose to normal organs were compared between CK and MBM for tumor number, size, shape and distance from the brainstem or chiasm. Results: The results showed that the mean brain dose was significantly smaller in MBM than CK. CI did not differ between MBM and CK; however, HI was significantly more ideal in CK (p = 0.000), and GI was significantly smaller in MBM (P = 0.000). LUF was larger in CK (p = 0.000) and HTOF and g was larger in MBM (p = 0.003, and 0.012). For single metastases, CK had significantly better HTOF (p = 0.000) and g (p = 0.002), but there were no differences for multiple tumors. Brain dose in MBM was significantly lower and CI was higher for tumors < 30 mm (p = 0.000 and 0.000), whereas HTOF and g for tumors < 10 mm were significantly smaller in CK (p = 0.041 and p = 0.016). Among oval tumors, brain dose, GI and LUF were smaller in MBM, but HTOF and g were smaller in CK. There were no particular trends for tumors close to the brainstem, but HTOF tended to be smaller in CK (0.03 vs. 0.29, p = 0.068) for tumors inside the brainstem. Conclusions: MBM can reduce the brain dose while achieving a dose distribution quality equivalent to that with CK.

A novel, end-to-end framework for avoiding collisions between the patient's body and gantry in proton therapy.

BACKGROUND: Administration of external radiation therapy via proton therapy systems carries a risk of occasional collisions between the patient's body and gantry, which is increased by the snout placed near the patient for better dose distribution. Although treatment planning software (TPS) can simulate controlled collisions, the computed tomography (CT) data used for treatment planning are insufficient given that collisions can occur outside the CT imaging region. Thus, imaging the three-dimensional (3D) surface outside the CT range and combining the data with those obtained by CT are essential for avoiding collisions. PURPOSE: To construct a prototype for 3D surface imaging and an end-to-end framework for preventing collisions between the patient's body and the gantry. METHODS: We obtained 3D surface data using a light sectioning method (LSM). By installing only cameras in front of the CT, we achieved LSM using the CT couch motion and preinstalled patient-positioning lasers. The camera image contained both sagittal and coronal lines, which are unnecessary for LSM and were removed by deep learning. We combined LSM 3D surface data and original CT data to create synthetic Digital Imaging and Communications in Medicine (DICOM) data. Subsequently, we compared the TPS snout auto-optimization using the original CT data with the synthetic DICOM data. RESULTS: The mean positional error for LSM of the arms and head was 0.7 ± 0.8  and 0.8 ± 0.8 mm for axial and sagittal imaging, respectively. The TPS snout auto-optimization indicated that the original CT data would cause collisions; however, the synthetic DICOM data prevented these collisions. CONCLUSIONS: The prototype system's acquisition accuracy for 3D surface data was approximately 1 mm, which was sufficient for the collision simulation. The use of a TPS with collision avoidance can help optimize the snout position using synthetic DICOM data. Our proposed method requires no external software for collision simulation and can be integrated into the clinical workflow to improve treatment planning efficiency.

Retrospective Analysis of the Areas Responsible for Light Flash and Odor During Proton Beam Therapy and Photon Therapy.

Background Abnormal sensations were frequently experienced by patients who received irradiation of the brain or head and neck region. We have previously suggested correlations with irradiation of the nasal cavity and retina. Purpose We performed a retrospective dose-volume histogram analysis focused on the brain and head and neck tumor to examine the relationship between these abnormal sensations and the details of irradiation. Methods Multivariate logistic regression models were applied for the presence or absence of light flash and odor. Gender, age, radiotherapy method (proton beam therapy vs. photon radiotherapy), dose of retina, optic nerve, chiasmatic gland, pituitary, nasal cavity, oral cavity, frontal lobe, parietal lobe, occipital lobe, temporal lobe, amygdala, and hippocampus were set as candidates of explanatory variables. Results Light flash and odor during radiotherapy have been suggested to be associated with younger age and retina and nasal cavity irradiation. Multivariate analyses including dose-volume histograms indicated that light flash was related to age, chiasmatic gland irradiation, and pituitary dose, and odor was related to age and nasal cavity irradiation. Conclusion Our results indicate that light flash during radiotherapy is caused by irradiation of the visual pathway and that odor is caused by irradiation of the nasal cavity or olfactory bulb.

Fully automated volumetric modulated arc therapy planning for locally advanced rectal cancer: feasibility and efficiency.

BACKGROUND: Volumetric modulated arc therapy (VMAT) for locally advanced rectal cancer (LARC) has emerged as a promising technique, but the planning process can be time-consuming and dependent on planner expertise. We aimed to develop a fully automated VMAT planning program for LARC and evaluate its feasibility and efficiency. METHODS: A total of 26 LARC patients who received VMAT treatment and the computed tomography (CT) scans were included in this study. Clinical target volumes and organs at risk were contoured by radiation oncologists. The automatic planning program, developed within the Raystation treatment planning system, used scripting capabilities and a Python environment to automate the entire planning process. The automated VMAT plan (auto-VMAT) was created by our automated planning program with the 26 CT scans used in the manual VMAT plan (manual-VMAT) and their regions of interests. Dosimetric parameters and time efficiency were compared between the auto-VMAT and the manual-VMAT created by experienced planners. All results were analyzed using the Wilcoxon signed-rank sum test. RESULTS: The auto-VMAT achieved comparable coverage of the target volume while demonstrating improved dose conformity and uniformity compared with the manual-VMAT. V30 and V40 in the small bowel were significantly lower in the auto-VMAT compared with those in the manual-VMAT (p < 0.001 and < 0.001, respectively); the mean dose of the bladder was also significantly reduced in the auto-VMAT (p < 0.001). Furthermore, auto-VMAT plans were consistently generated with less variability in quality. In terms of efficiency, the auto-VMAT markedly reduced the time required for planning and expedited plan approval, with 93% of cases approved within one day. CONCLUSION: We developed a fully automatic feasible VMAT plan creation program for LARC. The auto-VMAT maintained target coverage while providing organs at risk dose reduction. The developed program dramatically reduced the time to approval.

Synchronization of light flash with the irradiation pulse in proton beam therapy: A case report.

The correlation between sensory light flash and proton beam delivery was evaluated by measuring the timing of pulse beam delivery and light flash sensing using an event recorder in an 83-year-old patient receiving proton beam therapy (PBT) for nasopharyngeal adenoid cystic carcinoma. The treatment dose was 65 Gy (RBE) in 26 fractions with 2 ports, and both beams included the visual pathway (retina, optic nerve, chiasma). Measurements were obtained in 13 of the 26 fractions. The patient sensed a light flash in all 13 fractions and pressed the recorder button for 426 of the 430 pulsed beam deliveries, giving a sensing rate of 99.1%. The median duration of button-pressing of 0.3 s was almost the same as that of the beam pulse of 0.2 s, with a reaction time lag of 0.35 s. These results suggest a consistency between light flash during PBT and the timing of irradiation.

Formulation of Time-Dependent Cell Survival with Saturable Repairability of Radiation Damage.

This study aims to provide a model that compounds historically proposed ideas regarding cell survival irradiated with X rays or particles. The parameters used in this model have simple meanings and are closely related to cell death-related phenomena. The model is adaptable to a wide range of doses and dose rates and thus can consistently explain previously published cell survival data. The formulas of the model were derived by using five basic ideas: 1. "Poisson's law"; 2. "DNA affected damage"; 3. "repair"; 4. "clustered affected damage"; and 5. "saturation of reparability". The concept of affected damage is close to but not the same as the effect caused by the double-strand break (DSB). The parameters used in the formula are related to seven phenomena: 1. "linear coefficient of radiation dose"; 2. "probability of making affected damage"; 3. "cell-specific repairability", 4. "irreparable damage by adjacent affected damage"; 5. "recovery of temporally changed repairability"; 6. "recovery of simple damage which will make the affected damage"; 7. "cell division". By using the second parameter, this model includes cases where a single hit results in repairable-lethal and double-hit results in repairable-lethal. The fitting performance of the model for the experimental data was evaluated based on the Akaike information criterion, and practical results were obtained for the published experiments irradiated with a wide range of doses (up to several 10 Gy) and dose rates (0.17 Gy/h to 55.8 Gy/h). The direct association of parameters with cell death-related phenomena has made it possible to systematically fit survival data of different cell types and different radiation types by using crossover parameters.

Impact of Anatomical Position Errors on Dose Distribution in Head and Neck Radiotherapy and Robust Image Registration Against Anatomical Changes.

BACKGROUND/AIM: This study pursued two goals: Firstly, to search for anatomical structures strongly correlating with dose deterioration, and secondly to investigate the effectiveness of image registration focusing on critical anatomy by comparing it with a conventional method. The aim was to achieve robust image registration to correct for anatomical changes during treatment. PATIENTS AND METHODS: Twenty patients with head and neck cancer were enrolled, and 68 simulation computed tomography (CT) and rescan CT image sets were retrospectively analyzed. Forty volumetric-modulated arc therapy and intensity-modulated proton therapy plans were generated and recalculated according to the rescan CT to evaluate the dose effects of anatomical changes. Correlation coefficients were calculated for the relationships between the six-axis motion of the anatomy and the dose indices for the clinical target volume (CTV) and organs at risk. In the image registration, we compared a conventional method and target-based registration that limited the registration range to the CTV and vertebrae. RESULTS: The CTV coverage and spinal cord dose were correlated with the position error associated with the pitch and vertical position of the vertebrae, and the parotid gland and oral cavity dose were strongly correlated with the position error associated with the roll of the clivus and mandible. The target registration improved CTV coverage and suppressed the increase in dose to organs at risk compared with conventional methods. CONCLUSION: Monitoring vertebral alignment, the assessment and correction of positioning errors associated with the clivus and mandible position errors are important to ensure the quality of daily treatment. Target-based registration may allow for more robust image registration.

Novel Approach for Glycemic Management Incorporating Vibration Stimulation of Skeletal Muscle in Obesity.

Because obesity is associated with impaired glucose tolerance and type 2 diabetes (T2D), it is important to manage the blood glucose level at an early stage. Nevertheless, people with obesity have significantly lower resistance to muscle fatigue after exercise and exercise adherence. Therefore, we developed a novel "Relaxing-Vibration Training (RVT)" consisting of 25 postures using vibration stimulation of skeletal muscle and determined the feasibility of RVT for glycemic management. Thirty-one participants with obesity were enrolled in a controlled trial (CT) and experimental trial (ET) based on a 75 g oral glucose tolerance test (OGTT). During the CT, participants were required to rest in a quiet room. During the ET, the RVT program (50 Hz, 4 mm), consisting of 25 postures of relaxation and stretching on the vibratory platform, was performed for 40 min. Subsequently, the participants rested as in the CT. Subjective fatigue and muscle stiffness measurements and blood collection were conducted before and after RVT. In both the CT and ET, interstitial fluid (ISF) glucose concentrations were measured every 15 min for 2 h. The incremental area under the curve value of real-time ISF glucose during an OGTT was significantly lower in the ET than in the CT (ET: 7476.5 ± 2974.9, CT: 8078.5 ± 3077.7, effect size r = 0.4). Additionally, the levels of metabolic glucose regulators associated with myokines, muscle stiffness, and subjective fatigue significantly improved after RVT. This novel RVT suggests that it is effective in glycemic management with great potential to improve impaired glucose tolerance and T2D with obesity in the future.

Evaluation of basic characteristics of 3-mm dose equivalent measuring instrument for evaluating lens exposure dose in radiotherapy.

INTRODUCTION: Despite the development of DOSIRIS™, an eye lens dosimeter, the characteristics of DOSIRIS™ in the area of radiotherapy have not been investigated. The purpose of this study was to evaluate the basic characteristics of the 3-mm dose equivalent measuring instrument DOSIRIS™ in radiotherapy. METHODS: Dose linearity and energy dependence were evaluated for the irradiation system based on the calibration method of the monitor dosimeter. The angle dependence was measured by irradiating from a total of 18 directions. Interdevice variation was repeated three times by simultaneously irradiating five dosimeters. The measurement accuracy was based on the absorbed dose measured by the monitor dosimeter of the radiotherapy equipment. Absorbed doses were converted to 3-mm dose equivalents and compared with DOSIRIS™ measurements. RESULTS: Dose linearity was evaluated using the determination coefficient (R2 ) R2  = 0.9998 and 0.9996 at 6 and 10 MV, respectively. For energy dependence, although the therapeutic photons evaluated in this study had higher energies than in the previous studies and had a continuous spectrum, the response was equivalent to 0.2-1.25 MeV, well below the IEC 62387 limits. The maximum error at all angles was 15% (angle of 140°) and the coefficient of variation at all angles was 4.70%, which satisfies the standard of the thermoluminescent dosimeter measuring instrument. Accuracy of measurement was determined in terms of the measurement errors for DOSIRIS™ (3.2% and 4.3% at 6 and 10 MV, respectively,) using the 3-mm dose equivalent obtained from the theoretical value as a reference. The DOSIRIS™ measurements met the IEC standard which defines the measurement error of ±30% of the irradiance value in IEC 62387. CONCLUSIONS: We found that the characteristics of the 3-mm dose equivalent dosimeter in a high-energy radiation satisfy the IEC standards and have the same measurement accuracy as diagnostic areas such as Interventional Radiology.

Evaluation of the four-dimensional motion of lung tumors during end-exhalation breath-hold conditions using volumetric cine computed tomography images.

BACKGROUND AND PURPOSE: This study was performed to evaluate the four-dimensional motion of lung tumors during end-exhalation (EE) breath-holding (BH) using cine computed tomography (CT) and investigate the correlation between tumor and surrogate marker motions. MATERIALS AND METHODS: This study included 28 patients who underwent stereotactic body radiation therapy at our institution and were capable of 15-20 s of EE BH within a ±1.5-mm gating window with external markers. During EE BH with cine CT, 21 s of continuous data were acquired using 320-row multislice CT. Displacements in the tumor position during EE BH were assessed in the left-right (LR), anterior-posterior (AP), and superior-inferior (SI) directions. Pearson's correlation coefficient (r) between tumor motions during EE BH and diaphragm/external marker motions was also determined. RESULTS: The mean absolute maximum displacements of the tumor position during EE BH were 1.3 (range: 0.2-4.0), 1.9 (range: 0.3-12.0), and 1.3 (range: 0.1-7.2) mm in the LR, AP, and SI directions, respectively. The displacement of the tumor position in the AP direction was weakly correlated (|r| < 0.4) with the external marker and diaphragm displacements in many cases (proportions of 50% and 46%, respectively). CONCLUSION: We found some cases showing substantial displacement in lung tumor positions during EE BH, especially in the AP direction. Because these tumor position displacements did not correlate with surrogate markers and were difficult to detect, we recommend pretreatment evaluation of the four-dimensional motions of tumors during BH using cine CT.

Explainability and controllability of patient-specific deep learning with attention-based augmentation for markerless image-guided radiotherapy.

BACKGROUND: We reported the concept of patient-specific deep learning (DL) for real-time markerless tumor segmentation in image-guided radiotherapy (IGRT). The method was aimed to control the attention of convolutional neural networks (CNNs) by artificial differences in co-occurrence probability (CoOCP) in training datasets, that is, focusing CNN attention on soft tissues while ignoring bones. However, the effectiveness of this attention-based data augmentation has not been confirmed by explainable techniques. Furthermore, compared to reasonable ground truths, the feasibility of tumor segmentation in clinical kilovolt (kV) X-ray fluoroscopic (XF) images has not been confirmed. PURPOSE: The first aim of this paper was to present evidence that the proposed method provides an explanation and control of DL behavior. The second purpose was to validate the real-time lung tumor segmentation in clinical kV XF images for IGRT. METHODS: This retrospective study included 10 patients with lung cancer. Patient-specific and XF angle-specific image pairs comprising digitally reconstructed radiographs (DRRs) and projected-clinical-target-volume (pCTV) images were calculated from four-dimensional computer tomographic data and treatment planning information. The training datasets were primarily augmented by random overlay (RO) and noise injection (NI): RO aims to differentiate positional CoOCP in soft tissues and bones, and NI aims to make a difference in the frequency of occurrence of local and global image features. The CNNs for each patient-and-angle were automatically optimized in the DL training stage to transform the training DRRs into pCTV images. In the inference stage, the trained CNNs transformed the test XF images into pCTV images, thus identifying target positions and shapes. RESULTS: The visual analysis of DL attention heatmaps for a test image demonstrated that our method focused CNN attention on soft tissue and global image features rather than bones and local features. The processing time for each patient-and-angle-specific dataset in the training stage was ∼30 min, whereas that in the inference stage was 8 ms/frame. The estimated three-dimensional 95 percentile tracking error, Jaccard index, and Hausdorff distance for 10 patients were 1.3-3.9 mm, 0.85-0.94, and 0.6-4.9 mm, respectively. CONCLUSIONS: The proposed attention-based data augmentation with both RO and NI made the CNN behavior more explainable and more controllable. The results obtained demonstrated the feasibility of real-time markerless lung tumor segmentation in kV XF images for IGRT.

Light flash and odor during proton beam therapy for pediatric patients: a prospective observational study.

Light flash and odor during radiation therapy are well-known phenomena, but the details are poorly understood, particularly in pediatric patients. Therefore, we conducted a prospective observational study of these events in pediatric patients (age ≤20 years old) who received radiotherapy at our center from January 2019 to November 2021. Light flash and odor were evaluated using a patient-reported checklist including the presence, strength, and duration of the phenomenon, and color of light or type of odor. 53 patients who received proton therapy (n=47) and photon radiotherapy (n=6) were enrolled in this study. The median age of the patients was 10, ranged from 5 to 20. The patients who was able to see the light flash was 4, and all of them received retina irradiation. This was equivalent to 57% of the patients who received radiotherapy to retina (n=7). The light was bright and colored mainly blue and purple, which seemed to be consistent with Cherenkov light. Odor was sensed by 9 (17%) patients, and seven patients of the 9 received nasal cavity irradiation. This was equivalent to 41% of the patients who received nasal cavity irradiation (n=17). Other 2 patients received proton therapy to brain tumor. The odors were mainly described as plastic, burnt and disinfectant, which may be caused by ozone generated during irradiation. These data suggest that pediatric patients with retinal and nasal cavity irradiation frequently sense light flashes or odor. So adequate care is necessary so that these patients are not worried about this phenomenon.

Image preprocessing to improve the accuracy and robustness of mutual-information-based automatic image registration in proton therapy.

PURPOSE: We propose a method that potentially improves the outcome of mutual-information-based automatic image registration by using the contrast enhancement filter (CEF). METHODS: Seventy-six pairs of two-dimensional X-ray images and digitally reconstructed radiographs for 20 head and neck and nine lung cancer patients were analyzed retrospectively. Automatic image registration was performed using the mutual-information-based algorithm in VeriSuite®. Images were preprocessed using the CEF in VeriSuite®. The correction vector for translation and rotation error was calculated and manual image registration was compared with automatic image registration, with and without CEF. In addition, the normalized mutual information (NMI) distribution between two-dimensional images was compared, with and without CEF. RESULTS: In the correction vector comparison between manual and automatic image registration, the average differences in translation error were < 1 mm in most cases in the head and neck region. The average differences in rotation error were 0.71 and 0.16 degrees without and with CEF, respectively, in the head and neck region; they were 2.67 and 1.64 degrees, respectively, in the chest region. When used with oblique projection, the average rotation error was 0.39 degrees with CEF. CEF improved the NMI by 17.9 % in head and neck images and 18.2 % in chest images. CONCLUSIONS: CEF preprocessing improved the NMI and registration accuracy of mutual-information-based automatic image registration on the medical images. The proposed method achieved accuracy equivalent to that achieved by experienced therapists and it will significantly contribute to the standardization of image registration quality.

Abnormal sensation during total body irradiation: a prospective observational study.

Light flash and odor during radiotherapy are well-known phenomena. Two prospective observational studies have indicated that 55% of patients observed a light flash during irradiation of the retina and 27% of patients sensed an odor during radiotherapy for the nasal cavity. A prospective observational study was performed in all patients at our hospital who received total body irradiation (TBI) between January 2019 to October 2021. Light flash and odor during TBI were examined using the same method as that used in previous studies. A total of 32 patients received TBI during the study period. The patients had a median age of 41 (18-60) years, and included 20 males and 12 females. A survey checklist showed that 14 patients (44%) sensed light and 14 patients (44%) sensed odor during TBI,. The color of the light during irradiation was yellow in six cases, white in four cases, and blue in four cases. The intensity of the light was 2-5 (median 3, 1 is very weak, 5 is very strong) and the time over which the light flash was felt was 4-60 s (median 10 s). Two patients each sensed smells of plastic, ozone and bleach, and others sensed one smell each. The intensity of the odor was 1-4 (median 3, 1 is very weak, 5 is very strong) and the time over which the odor was sensed was 1-25 s (median 3 s). We conclude that light flashes and odors are each sensed by 44% of patients during TBI. Various types of light flashes and odors were reported in this study.

Analysis of diaphragm movements to specify geometric uncertainties of respiratory gating near end-exhalation for irradiation fields involving the liver dome.

BACKGROUND AND PURPOSE: The technique of gating near end-exhalation is commonly adopted to reduce respiration-associated geometric uncertainties for particle beam therapy. However, for irradiation fields involving the liver dome, how diaphragm movements generating liver-lung interface change, alongside geometric uncertainties, remain unspecified. METHODS AND MATERIALS: Patients receiving respiratory-gated computed tomography (RGCT) with four-dimensional computed tomography (4DCT) scans during simulation were retrospectively reviewed. Differences (Δ) between RGCT and 4DCT images, including diaphragm displacements and liver-lung interface changes, were investigated to specify geometric uncertainties during early inhalation phases. Craniocaudal displacements (Δy, in sagittal/coronal planes) of diaphragm segments (dorsal/ventral/right lateral/medial), liver area changes (ΔA, in axial planes), and liver extent changes in specific directions of incidence (Δr, in axial planes) were analyzed. RESULTS: Altogether, 162 patients received simulating RGCT and 4DCT scans. In 22 of them, both images involved the liver dome. For most cases during early inhalation phases, the Δy values in the dorsal diaphragm were significantly greater than those in the ventral diaphragm (p < 0.05), the ΔA values were significantly enlarged with inhalation progressing (p < 0.05), and the Δr values in the dorsal direction were significantly larger than those in the ventral direction (p < 0.05). These results suggested that the dorsal diaphragm moves earlier and more in a caudal direction than the ventral diaphragm during early inhalation phases. CONCLUSIONS: For respiratory-gated radiotherapy near end-exhalation and irradiation fields involving the liver dome, components of geometric uncertainties are temporospatial, including diaphragm segment movements, inhalation phases of irradiation, and beam angles of incidence.

Olfactory Sensations During Proton and Photon Radiotherapy: A Multicenter Prospective Observational Study.

PURPOSE: Patients often report a sense of smell during radiation therapy (RT), but the details of these events are not well understood. The purpose of the study was to evaluate events of smell during photon RT and proton beam therapy (PBT). METHODS AND MATERIALS: The subjects were all adult patients (≥20 years old) treated with photon RT or PBT at two centers from January 2019 to August 2020, with the exclusion of those with communication difficulties or olfactory abnormality. The presence of smell, odor type, intensity (five levels), and time period was examined prospectively using a weekly checklist. RESULTS: A total of 649 courses were examined in 620 patients who received photon RT (n=415) or PBT (n=205). A smell during the procedure was sensed by 51 patients (8.2%). In multivariate logistic regression analysis, nasal cavity dose (p=0.002), age (p<0.001), and photon RT (p=0.018) were identified as significant factors associated with a sense of smell. Smell occurred in only 23/515 patients (4.5%) in whom the nasal cavity was not irradiated, but in 4/19 (21.1%) and 24/86 (27.9%) with nasal cavity maximum isodose lines of 10%-50% and 60%-100%, respectively. Patients who received photon RT sensed a smell (43/415; 10.4%) more frequently than those treated with PBT (8/205; 3.9%). Of the 51 patients who sensed a smell, 32 (63%) reported a burnt smell, eight (16%) a chemical smell, two (4%) a sour smell, and nine another smell (copier machine, sweet, garbage, etc.). CONCLUSIONS: The sense of a smell appears to be common during RT and this sensation is significantly associated with the nasal cavity dose, younger age, and photon RT.

Detection of anatomical changes using two-dimensional x-ray images for head and neck adaptive radiotherapy.

PURPOSE: To develop a system for detecting anatomical changes using two-dimensional (2D) x-ray images. METHODS: Ten patients with head and neck cancer were retrospectively analyzed using 2D x-ray and cone-beam computed tomography (CBCT) images. The 2D x-ray images were acquired daily, whereas the CBCT images were acquired weekly during the treatment period. The developed system imported the 2D x-ray images obtained on the initial treatment day and on another day, and thereafter converted them into the water equivalent thickness (WET) using the conversion table. The difference between the WET images for the first and other treatment days (ΔWET) was calculated as the quantitative value for anatomical changes and visualized to recognize the anatomical change location. We compared ΔWET and the difference in the lateral neck distance (ΔLND) on the corresponding CBCT images. ΔLND was used as the ground truth for anatomical changes. ΔWET and ΔLND were measured at the first cervical vertebra (C1) and the tumor center (TC). C1 and TC were selected to observe the volume changes in the parotid gland and tumor, respectively. Sensitivity and specificity were calculated to evaluate the performance of the 2D-WET system. The cut-off values of WET and LND were set to 2-10 mm. Furthermore, intensity-modulated proton therapy (IMPT) plans for six patients with rescan CT images were generated. The IMPT plans on the rescan CT images were compared to the original plans on simulation CT using the dosimetric parameters for the target and the organs at risk. RESULTS: The mean differences between ΔWET and ΔLND for C1 and TC were -0.62 ± 1.66 mm and -0.93 ± 1.28 mm (mean ± 1 SD), respectively. ΔWET in the proposed system was in good agreement with ΔLND using the CBCT images. In the sensitivity and specificity results for C1 and TC with cut-off values from 2 to 10 mm, the sensitivity was >85% for all cut-off values, while the specificity was >90% at 5-10 mm and <90% at less than 5 mm. The average ΔWET at the time of replanning was 12.8 mm which resulted in maximum dose increase in the spinal cord D1cc by 8.4 Gy, the parotid gland D50 by 26.6 Gy, and the oral cavity D50 by 23.2 Gy. CONCLUSIONS: We developed a new system for detecting anatomical changes using 2D x-ray images. The developed system with ΔWET showed an agreement with ΔLND at C1 and TC with an average difference of less than 1 mm. ΔWET detected anatomical changes with high sensitivity and specificity with a cut-off value of 5-10 mm. This system can monitor daily anatomical changes without causing high exposure to patients and requiring any inefficient work, and it can be applied to daily online adaptive proton beam therapy and triggered adaptive radiotherapy.