The serum tenascin C level is a marker of metabolic disorder-related inflammation affecting pancreatic cancer prognosis.

Obesity is a risk factor for pancreatic cancer development, partly due to the tissue environment of metabolic disorder-related inflammation. We aimed to detect a tissue environment marker triggered by obesity-related metabolic disorders related to pancreatic cancer progression. In murine experiments, Bl6/j mice fed a normal diet (ND) or a high-fat diet (HFD) were orthotopically injected with mPKC1, a murine-derived pancreatic cancer cell line. We used stocked sera from 140 pancreatic cancer patients for analysis and 14 colon polyp patients as a disease control. Compared with ND-fed mice, HFD-fed mice exhibited obesity, larger tumors, and worse prognoses. RNA sequencing of tumors identified tenascin C (TNC) as a candidate obesity-related serum tissue environment marker with elevated expression in tumors of HFD-fed mice. Serum TNC levels were greater in HFD-fed mice than in ND-fed mice. In pancreatic cancer patients, serum TNC levels were greater than those in controls. The TNC-high group had more metabolic disorders and greater CA19-9 levels than did the TNC-low group. There was no relationship between serum TNC levels and disease stage. Among 77 metastatic patients treated with chemotherapy, a high serum TNC concentration was an independent poor prognostic factor. Pancreatic cancer patients with high serum TNC levels experienced progression more rapidly.

Psychological stress associated with skin marking during radiotherapy on breast cancer patients.

INTRODUCTION: This study aimed to further understand the psychological distress associated with skin marking during radiotherapy among patients with breast cancer. The potential benefits of skin mark-free radiotherapy were also explored. MATERIALS AND METHODS: The study population included female breast cancer patients scheduled for radiation therapy and skin marking. A 12-item survey was administered, encompassing demographics (age, treatment site and mode, and duration of hospital visits), awareness of skin marking, stress induced by skin marking in various life contexts, and perceived advantages of a skin mark-free alternative. Responses were recorded on a 5-point Likert scale. RESULTS: The survey was completed by 107 patients, of whom 90 (84%) underwent whole breast irradiation, 15 (14%) received breast/chest wall and supraclavicular lymph node irradiation, and 2 (2%) were unspecified. The common sources of stress were from the presence of skin markings (33%), bathing (41%), clothing selection (25%), and skincare (30%), whereas 17 patients (16%) were not stressed by any of those factors. Meanwhile, 73% of patients reported taking precautions to prevent the skin marks from fading. Most patients (63%, n = 76) expressed preference for a skin mark-free radiotherapy option, with many willing to spend extra finances and time for this. CONCLUSIONS: A significant proportion of female breast cancer patients experience stress from skin markings in various aspects of their daily lives. A preference for skin mark-free radiotherapy was noted among many patients, that next-generation technologies, such as surface-guided radiotherapy, could alleviate patient stress. IMPLICATIONS FOR PRACTICE: The need for permanent or temporary skin markings in the era of state-of-the-art imaging technology should be reconsidered.

Clinical evaluation of deep learning and atlas-based auto-segmentation for organs at risk delineation.

Manual delineation of organs at risk and clinical target volumes is essential in radiotherapy planning. Atlas-based auto-segmentation (ABAS) algorithms have become available and been shown to provide accurate contouring for various anatomical sites. Recently, deep learning auto-segmentation (DL-AS) algorithms have emerged as the state-of-the-art in medical image segmentation. This study aimed to evaluate the effect of auto-segmentation on the clinical workflow for contouring different anatomical sites of cancer, such as head and neck (H&N), breast, abdominal region, and prostate. Patients with H&N, breast, abdominal, and prostate cancer (n = 30 each) were enrolled in the study. Twenty-seven different organs at four sites were evaluated. RayStation was used to apply the ABAS. Siemens AI-Rad Companion Organs RT was used to apply the DL-AS. Evaluations were performed with similarity indices using geometric methods, time-evaluation, and qualitative scoring visual evaluations by radiation oncologists. The DL-AS algorithm was more accurate than ABAS algorithm on geometric indices for half of the structures. The qualitative scoring results of the two algorithms were significantly different, and DL-AS was more accurate on many contours. DL-AS had 41%, 29%, 86%, and 15% shorter edit times in the HnN, breast, abdomen, and prostate groups, respectively, than ABAS. There were no correlations between the geometric indices and visual assessments. The time required to edit the contours was considerably shorter for DL-AS than for ABAS. Auto-segmentation with deep learning could be the first step for clinical workflow optimization in radiotherapy.

Dosimetric Comparison of 3D Conformal Radiotherapy (3D-CRT), Intensity-Modulated Radiotherapy (IMRT), and Volumetric-Modulated Arc Therapy (VMAT) in Cardiac-Sparing Whole Lung Irradiation.

Introduction Whole lung irradiation (WLI) is used for the treatment of lung metastasis in Wilms tumor and Ewing sarcoma; however, cardiac complications are one of the concerns. We report the dosimetric advantages of WLI using volumetric-modulated arc therapy (VMAT) and present a dosimetric comparison of VMAT with anteroposterior-posteroanterior (AP-PA) and static-field intensity-modulated radiation therapy (IMRT). Additionally, we evaluated the dosimetric impact of respiratory motion and intra-fractional motion during VMAT treatment. Methods Seven patients were recruited in this study. AP-PA, IMRT, one-isocenter (1-IC) VMAT, and 2-IC VMAT were planned on the maximum inspiration and expiration CT, respectively. The prescribed dose was 15 Gy in 10 fractions. To determine the effects of respiratory motion, the CT series was replaced and the dose was evaluated while maintaining the beam information. To determine the effect of patient motion, perturbed dose calculations were performed using a two-IC VMAT. The perturbation doses were calculated by shifting only the IC of the one side beam by 3 mm or 5 mm in the right-to-left (RL) direction. Results The mean heart dose was 1467.0 cGy, 790.0 cGy, 764.2 cGy, and 738.4 cGy for AP-PA, IMRT, 1-IC VMAT, and 2-IC VMAT, respectively. When the expiration CT plan was recalculated with inspiration CT, Dmax increased approximately by 8%. In the 2-IC VMAT plan, the D50%, D98%, and D2% dose differences were within ±2%, even with a 5 mm IC shift. Conclusion We confirmed a significant dosimetric advantage of VMAT over other techniques. 2-IC VMAT should be considered an effective treatment option during irradiation for large target volumes.

Residual image registration error by fiducial markers in accelerated partial breast irradiation using C-arm linac: a phantom study.

External beam accelerated partial breast irradiation (APBI) is an alternative treatment for patients with early-stage breast cancer. The efficacy of image-guided radiotherapy (IGRT) using fiducial markers, such as gold markers or surgical clips, has been demonstrated. However, the effects of respiratory motion during a single fraction have not been reported. This study aimed to evaluate the residual image registration error of fiducial marker-based IGRT by respiratory motion and propose a suitable treatment strategy. We developed an acrylic phantom embedded with surgical clips to verify the registration error under moving conditions. The frequency of the phase difference in the respiratory cycle due to sequential acquisition was verified in a preliminary study. Fiducial marker-based IGRT was then performed in ten scenarios. The residual registration error (RRE) was calculated on the basis of the differences in the coordinates of clips between the true position if not moved and the last position. The frequencies of the phase differences in 0.0-0.99, 1.0-1.99, 2.0-2.99, 3.0-3.99, and 4.0-5.0 mm were 23%, 24%, 22%, 20%, and 11%, respectively. When assuming a clinical case, the mean RREs for all directions were within 1.0 mm, even if respiratory motion of 5 mm existed in two axes. For APBI with fiducial marker-based IGRT, the introduction of an image registration strategy that employs stepwise couch correction using at least three orthogonal images should be considered.

Assessment of visual feedback system for reproducibility of voluntary deep inspiration breath hold in left-sided breast radiotherapy.

INTRODUCTION: Deep inspiration breath-hold (DIBH) for left-sided breast cancer radiotherapy reduces the dose exposure of the heart and left anterior descending coronary artery. DIBH requires the patient to maintain an adequate breath-hold position during their daily radiotherapy fraction. This study aimed to assess the reproducibility of the breath-hold position by implementing DIBH with visual feedback (VF) system. METHODS: Forty-three patients who underwent left-sided radiotherapy with DIBH were reviewed. Data from 35 patients who underwent DIBH with VF (VF-DIBH) were compared with data from 8 patients who underwent DIBH with audio coaching (AC-DIBH). Reproducibility during radiotherapy was evaluated using the portal images obtained. Images were acquired daily during the tangential field treatment with DIBH. The distances between the field edge and chest wall at the central beam axis were manually measured on the portal image and digital reconstruction radiograph (DRR). The displacements of the chest wall during radiotherapy were assessed by subtracting the measurement made on the portal image from the DRR measurement. The overall average distances for the VF-DIBH and AC-DIBH cohorts were compared to assess reproducibility. The statistical analysis was performed using Mann-Whitney U tests (p < 0.05). RESULTS: The mean chest wall displacement (±2 SD) was 0.59 ± 3.64 mm for VF-DIBH and 2.09 ± 4.96 mm for AC-DIBH, respectively. This value differed significantly between the VF-DIBH and AC-DIBH cohorts (p < 0.001). CONCLUSION: In DIBH radiotherapy, the implementation of VF was confirmed to improve breath-hold position reproducibility, and the utility of VF for DIBH was demonstrated.

Direct energy spectrum measurement of X-ray from a clinical linac.

A realistic X-ray energy spectrum is essential for accurate dose calculation using the Monte Carlo (MC) algorithm. An energy spectrum for dose calculation in the radiation treatment planning system is modeled using the MC algorithm and adjusted to obtain acceptable agreement with the measured percent depth dose (PDD) and off-axis ratio. The simulated energy spectrum may not consistently reproduce a realistic energy spectrum. Therefore, direct measurement of the X-ray energy spectrum from a linac is necessary to obtain a realistic spectrum. Previous studies have measured low photon fluence directly, but the measurement was performed with a nonclinical linac with a thick target and a long target-to-detector distance. In this study, an X-ray energy spectrum from a clinical linac was directly measured using a NaI(Tl) scintillator at an ultralow dose rate achieved by adjusting the gun grid voltage. The measured energy spectrum was unfolded by the Gold algorithm and compared with a simulated spectrum using statistical tests. Furthermore, the PDD was calculated using an unfolded energy spectrum and a simulated energy spectrum was compared with the measured PDD to evaluate the validity of the unfolded energy spectrum. Consequently, there was no significant difference between the unfolded and simulated energy spectra by nonparametric, Wilcoxon's rank-sum, chi-square, and two-sample Kolmogorov-Smirnov tests with a significance level of 0.05. However, the PDD calculated from the unfolded energy spectrum better agreed with the measured compared to the calculated PDD results from the simulated energy spectrum. The adjustment of the incident electron parameters using MC simulation is sensitive and takes time. Therefore, it is desirable to obtain the energy spectrum by direct measurement. Thus, a method to obtain the realistic energy spectrum by direct measurement was proposed in this study.

The influence of respiratory motion on dose distribution in accelerated partial breast irradiation using volumetric modulated arc therapy.

PURPOSE: Accelerated partial breast irradiation (APBI) is alternative treatment option for patients with early stage breast cancer. The interplay effect on volumetric modulated arc therapy APBI (VMAT-APBI) has not been clarified. This study aimed to evaluate the feasibility of VMAT-APBI for patients with small breasts and investigate the amplitude of respiratory motion during VMAT-APBI delivery that significantly affects dose distribution. METHODS: The VMAT-APBI plans were generated with 28.5 Gy in five fractions. We performed patient-specific quality assurance using Delta4 phantom under static conditions. We also measured point dose and dose distribution using the ionization chamber and radiochromic film under static and moving conditions of 2, 3 and 5 mm. We compared the measured and calculated point doses and dose distributions by dose difference and gamma passing rates. RESULTS: A total of 20 plans were generated; the dose distributions were consistent with those of previous reports. For all measurements under static conditions, the measured and calculated point doses and dose distributions showed good agreement. The dose differences for chamber measurement were within 3%, regardless of moving conditions. The mean gamma passing rates with 3%/2 mm criteria in the film measurement under static conditions and with 2 mm, 3 mm, and 5 mm of amplitude were 95.0 ± 2.0%, 93.3 ± 3.3%, 92.1 ± 6.2% and 84.8 ± 7.8%, respectively. The difference between 5 mm amplitude and other conditions was statistically significant. CONCLUSIONS: Respiratory management should be considered for the risk of unintended dose distribution if the respiratory amplitude is >5 mm.

Estimation of the cable effect in megavoltage photon beam by measurement and Monte Carlo simulation.

PURPOSE: Ionization chambers are widely used for dosimetry with megavoltage photon beams. Several properties of ionization chambers, including the cable effect, polarity effect, and ion recombination loss, are described in standard dosimetry protocols. The cable effect is categorized as the leakage current and Compton current, and careful consideration of these factors has been described not only in reference dosimetry but also in large fields. However, the mechanism of Compton current in the cable has not been investigated thoroughly. The cable effect of ionization chambers in 6 MV X-ray beam was evaluated by measurement, and the mechanism of Compton current was investigated by Monte Carlo simulation. MATERIALS AND METHODS: Four PTW ionization chambers (TM30013, TM31010, TM31014, and TM31016) with the same type of mounted cable, but different ionization volumes, were used to measure output factor (OPF) and cable effect measurement. The OPF was measured to observe any variation resulting from the cable effect. The cable effect was evaluated separately for the leakage current and Compton current, and its charge per absorbed dose to water per cable length was estimated by a newly proposed method. The behavior of electrons and positrons in the core wire was analyzed and the Compton current for the photon beam was estimated by Monte Carlo simulation. RESULTS: In OPF measurement, the difference in the electrometer readings by polarity became obvious for the mini- or microchamber and its difference tended to be larger for a chamber with a smaller ionization volume. For the cable effect measurement, it was determined that the contribution of the leakage current to the cable effect was ignorable, while the Compton current was dominant. The charge due to the Compton current per absorbed dose to water per cable length was estimated to be 0.36 ± 0.03 pC Gy-1  cm-1 for PTW ionization chambers. As a result, the contribution of the Compton current to the electrometer readings was estimated to be 0.002% cm-1 for the Farmer-type, 0.011% cm-1 for the scanning, and 0.088% cm-1 for microchambers, respectively. By the simulation, it was determined that the Compton current for MV x-ray could be explained by not only recoil electrons due to Compton scattering but also positron due to pair production. The Compton current estimated by the difference in outflowing and inflowing charge was 0.45 pC Gy-1  cm-1 and was comparable with the measured value. CONCLUSION: The cable effect, which includes the leakage current and Compton current, was quantitatively estimated for several chambers from measurements, and the mechanism of Compton current was investigated by Monte Carlo simulation. It was determined that the Compton current is a dominant component of the cable effect and its charge is consistently positive and nearly the same, irrespective of the ionization chamber volume. The contribution of Compton current to the electrometer readings was estimated for chambers. The mechanism of Compton current was analyzed and it was confirmed that the Compton current can be estimated from the difference in outflowing and inflowing charge to and from the core wire.

Dosimetric evaluation of deep inspiration breath hold for left-sided breast cancer: analysis of patient-specific parameters related to heart dose reduction.

Deep inspiration breath hold (DIBH) is a common method used worldwide for reducing the radiation dose to the heart. However, few studies have reported on the relationship between dose reduction and patient-specific parameters. The aim of this study was to compare the reductions of heart dose and volume using DIBH with the dose/volume of free breathing (FB) for patients with left-sided breast cancer and to analyse patient-specific dose reduction parameters. A total of 85 Asian patients who underwent whole-breast radiotherapy after breast-conserving surgery were recruited. Treatment plans for FB and DIBH were retrospectively generated by using an automated breast planning tool with a two-field tangential intensity-modulated radiation therapy technique. The prescribed dose was 50 Gy in 25 fractions. The dosimetric parameters (e.g., mean dose and maximum dose) in heart and lung were extracted from the dose-volume histogram. The relationships between dose-volume data and patient-specific parameters, such as age, body mass index (BMI), and inspiratory volume, were analyzed. The mean heart doses for the FB and DIBH plans were 1.56 Gy and 0.75 Gy, respectively, a relative reduction of 47%. There were significant differences in all heart dosimetric parameters (p < 0.001). For patients with a high heart dose in the FB plan, a relative reduction of the mean heart dose correlated with inspiratory volume (r = 0.646). There was correlation between the relative reduction of mean heart dose and BMI (r = -0.248). We recommend considering the possible feasibility of DIBH in low BMI patients because the degree of benefit from DIBH varied with BMI.

Evaluation of gantry angle during respiratory-gated VMAT using triggered kilovoltage x-ray image.

Respiratory-gated volumetric modulated arc therapy (gated VMAT) involves further complexities to the dose delivery process because the gantry rotation must repeatedly stop and restart according to the gating signals. In previous studies, the gantry rotation performances were evaluated by the difference between the plan and the machine log. However, several reports pointed out that log analysis does not sufficiently replicate the machine performance. In this report, a measurement-based quality assurance of the relation between the gantry angle and gate-on or gate-off using triggered kilovoltage imaging and a cylinder phantom with 16 ball bearings is proposed. For the analysis, an in-house program that estimates and corrects the phantom offset was developed. The gantry angle in static and gated arc delivery was compared between the machine log and the proposed method. The gantry was set every 5 deg through its full motion range in static delivery, and rotated at three speeds (2, 4 and 6 deg s-1 ) with different gating intervals (1.5 or 3.0 s) in gated arc delivery. The mean and standard deviation of the angular differences between the log and the proposed method was -0.05 deg ± 0.12 deg in static delivery. The mean of the angular difference was within ±0.10 deg and the largest difference was 0.41 deg in gated arc delivery. The log records the output of the encoder so that miscalibration and mechanical sagging will be disregarded. However, the proposed method will help the users to detect the mechanical issues due to the repeated gantry stops and restarts in gated VMAT.

Exercise-induced oxidative DNA damage and lymphocytopenia in sedentary young males.

UNLABELLED: Post high-intensity exercise lymphocytopenia is well documented, but its underlying mechanisms have not been fully elucidated. A possible mechanism is a reactive oxygen species-induced DNA damage after high-intensity exercise. Furthermore, lymphocyte apoptosis related to DNA damage might contribute to exercise-induced lymphocytopenia. PURPOSE: This study examined lymphocytopenia, lymphocyte oxidative DNA damage, and apoptosis in young healthy sedentary males after acute high-intensity exercise. METHOD: Fifteen subjects exercised on bicycle ergometers for 1 h at 75% of their VO2max. Venous blood samples were taken before exercise (PRE) and hourly after exercise until 4 h (P0-P4). Lymphocyte counts, oxidative DNA damage evaluated using the Comet assay with human 8-oxoguanine DNA glycosylase, and serum lipid peroxide (LPO) concentration were measured. Furthermore, lymphocyte superoxide, Fas receptor (CD95), and Annexin-V-positive lymphocyte apoptosis cells were measured in 10 subjects who exercised and gave blood samples as described above. RESULTS: Lymphocyte counts became significantly lower than the PRE value (P < 0.05): 20.4% at P1, 24.3% at P2, and 16.3% at P3. Moreover, LPO significantly increased by P2 (P < 0.05): 1.6-fold. The % DNA in tail, indicating oxidative DNA damage, was significantly higher at P3 (54.3 +/- 12.8%) than at PRE (42.6 +/- 11.1%, P < 0.05). The lymphocyte superoxide level was significantly higher (51.3%) than the PRE value (P < 0.05). Neither CD95 nor Annexin-V-positive cells were significantly different than the PRE value. CONCLUSION: Results of this study suggest that lymphocyte oxidative DNA damage can relate to lymphocytopenia, although DNA damage was not associated with apoptosis in healthy young sedentary males.