To investigate the impact of the effective radiation dose to immune cells (EDIC) and gross tumor volume (GTV) on lymphopenia and survival in patients with locally advanced esophageal squamous cell carcinoma (LAESCC). Between January 2013 and December 2020, 272 LAESCC patients were treated with definitive radiotherapy in two institutions. Based on radiation doses to the lungs, heart, and body region scanned, EDIC was calculated as an equal uniform dose to the total blood considering blood flow and fraction effect. The radiotherapy plan was used to calculate the GTVs. Lymphopenia was graded based on the lowest lymphocyte count during RT. The overall survival (OS), progress-free survival (PFS), and local recurrence-free survival (LRFS) were analyzed statistically. The lowest lymphocyte count was significantly correlated with EDIC (r= -0.389, p < .001) and GTV (r= -0.211, p < .001). Lymphopenia, EDIC, and GTV are risk factors for patients with ESCC. In a Kaplan-Meier analysis with EDIC and GTV as stratification factors, lymphopenia was not associated with OS in the EDIC>12.9 Gy group (p = .294)and EDIC ≤ 12.9 Gy group, and it was also not associated with OS in GTV>68.8 cm3 group (p = .242) and GTV ≤ 68.8 cm3 group(p = .165). GTV and EDIC had an impact on the relationship between lymphopenia and OS in patients with LAESCC undergoing definitive RT. Poorer OS, PFS, and LRFS are correlated with lymphopenia, higher EDIC, and larger GTV.

BACKGROUND: To explore the correlation between effective dose to immune cells (EDIC) and vertebral bone marrow dose and hematologic toxicity (HT) for esophageal squamous cell carcinoma (ESCC) during neoadjuvant chemoradiotherapy (nCRT).
METHODS: The study included 106 ESCC patients treated with nCRT. We collected dosimetric parameters, including vertebral body volumes receiving 10-40 Gy (V10, V20, V30, V40) and EDIC and complete blood counts. Associations of the cell nadir and dosimetric parameters were examined by linear and logistic regression analysis. The receiver operating characteristic (ROC) curves were used to determine the cutoff values for the dosimetric parameters.
RESULTS: During nCRT, the incidence of grade 3-4 lymphopenia, leukopenia, and neutropenia was 76.4%, 37.3%, and 37.3%, respectively. Patients with EDIC ≤ 4.63 Gy plus V10 ≤ 140.3 ml were strongly associated with lower risk of grade 3-4 lymphopenia (OR, 0.050; P < 0.001), and patients with EDIC ≤ 4.53 Gy plus V10 ≤ 100.9 ml were strongly associated with lower risk of grade 3-4 leukopenia (OR, 0.177; P = 0.011), and patients with EDIC ≤ 5.79 Gy were strongly associated with lower risk of grade 3-4 neutropenia (OR, 0.401; P = 0.031). Kaplan-Meier analysis showed that there was a significant difference among all groups for grade 3-4 lymphopenia, leukopenia, and neutropenia (P < 0.05).
CONCLUSIONS: The dose of vertebral bone marrow irradiation and EDIC were significantly correlated with grade 3-4 leukopenia and lymphopenia, and EDIC was significantly correlated with grade 3-4 neutropenia. Reducing vertebral bone marrow irradiation and EDIC effectively reduce the incidence of HT.

This study employed a commercial software velocity to perform deformable registration and dose calculation on deformed CT images, aiming to assess the accuracy of dose delivery during the radiotherapy for lung cancers. A total of 20 patients with lung cancer were enrolled in this study. Adaptive CT (ACT) was generated by deformed the planning CT (pCT) to the CBCT of initial radiotherapy fraction, followed by contour propagation and dose recalculation. There was not significant difference between volumes of GTV and CTV calculated from the ACT and pCT. However, significant differences in dice similarity coefficient (DSC) and coverage ratio (CR) between GTV and CTV were observed, with lower values for GTV volumes below 15 cc. The mean differences in dose corresponding to 95% of the GTV, GTV-P, CTV, and CTV-P between ACT and pCT were - 0.32%, 4.52%, 2.17%, and 4.71%, respectively. For the dose corresponding to 99%, the discrepancies were - 0.18%, 8.35%, 1.92%, and 24.96%, respectively. These differences in dose primarily appeared at the edges of the target areas. Notably, a significant enhancement of dose corresponding to 1 cc for spinal cord was observed in ACT, compared with pCT. There was no statistical difference in the mean dose of lungs and heart. In general, for lung cancer patients, anatomical motion may result in both CTV and GTV moving outside the original irradiation region. The dose difference within the original target area was small, but the difference in the planning target area was considerable.

BACKGROUND: Innovations in cancer treatment have contributed to the improved survival rate of cancer patients. The cancer survival rates have been growing and nearly two third of those survivors have been exposed to clinical radiation during their treatment. The study of long-term radiation effects, especially secondary cancer induction, has become increasingly important. An accurate assessment of out-of-field/peripheral dose (PDs) is necessary to estimate the risk of second cancer after radiotherapy and the damage to the organs at risk surrounding the planning target volume. This study was designed to measure the PDs as a function of dose, distances, and depths from Telecobalt-60 (Co-60) beam in water phantom using thermoluminescent dosimeter-100 (TLD-100).
METHODS: The PDs were measured for Co-60 beam at specified depths of 0 cm (surface), 5 cm, 10 cm, and 15 cm outside the radiation beam at distances of 5, 10, and 13 cm away from the radiation field edge using TLD-100 (G1 cards) as detectors. These calibrated cards were placed on the acrylic disc in circular tracks. The radiation dose of 2000 mGy of Co-60 beam was applied inside 10 × 10 cm2 field size at constant source to surface distance (SSD) of 80 cm.
RESULTS: The results showed maximum and minimum PDs at surface and 5 cm depth respectively at all distances from the radiation field edge. Dose distributions out of the field edge with respect to distance were isotropic. The decrease in PDs at 5 cm depth was due to dominant forward scattering of Co-60 gamma rays. The increase in PDs beyond 5 cm depth was due to increase in the irradiated volume, increase in penumbra, increase in source to axis distance (SAD), and increase in field size due to inverse square factor.
CONCLUSIONS: It is concluded that the PDs depends upon depth and distance from the radiation field edge. All the measurements show PDs in the homogenous medium (water); therefore, it estimates absorbed dose to the organ at risk (OAR) adjacent to cancer tissues/planning target volume (PTV). It is suggested that PDs can be minimized by using the SAD technique, as this technique controls sources of scattered radiation like inverse square factor and effect of penumbra up-to some extent.

BACKGROUND: Volumetric modulated arc therapy (VMAT) is a novel form of IMRT, which can deliver more accurate dose distribution and shorten treatment time. Compared to MRI-guided adaptive brachytherapy, which is recommended as gold standard imaging for cervical cancer contours, CT-guided adaptive brachytherapy (CTGAB) is more available, more widespread, and more affordable in many centers. This study aims to retrospectively analyze the efficacy and the safety of VMAT combined with CTGAB for patients with locally advanced cervical cancer.
METHODS: This study retrospectively analyzed 102 patients with locally advanced cervical cancer who underwent VMAT and CTGAB. Clinical outcomes including local control (LC), overall survival (OS) and progression-free survival (PFS), tumor response to treatment evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.1), and toxicities including gastrointestinal toxicity, urinary toxicity and hematologic toxicity evaluated by the Common Terminology Criteria for Adverse Events (CTCAE) (version 5.0) were analyzed. The Kaplan-Meier method was used to calculate LC, OS, and PFS.
RESULTS: Median follow-up time was 19 months. Complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) occurred in 68 (66.7%), 24 (23.5%), 4 (3.92%), and 6 (5.88%), respectively. The 2-year and 3-year OS were 89.6% and 83%, respectively. The 2-year and 3-year PFS were 84.2% and 74.3%, respectively. The 2-year and 3-year LC were 90.1% and 79.3%, respectively. The average cumulative D2cm3 in the rectum, the bladder, the colon, and the small intestine were 78.07 (SD: 0.46) Gy, 93.20 (SD: 0.63) Gy, 63.55 (SD: 1.03) Gy and 61.07 (SD: 0.75) Gy, respectively. The average cumulative D90% of the high-risk clinical target volume (HR-CTV) was 92.26 (SD: 0.35) Gy. Grade ≥ 3 gastrointestinal and urinary toxicities occurred in 4.9% and 0.98%, respectively. 1.96% of patients were observed grade ≥ 4 gastrointestinal toxicities and none of the patients observed grade ≥ 4 urinary toxicities.
CONCLUSIONS: VMAT combined with CTGAB for locally advanced cervical cancer was an effective and safe treatment method, which showed satisfactory LC, OS, PFS, and acceptable toxicities.

To explore the relationships between gastrointestinal radiation injuries of pancreatic cancer patients treated with TOMO and dose-volume histogram parameters prospectively. Seventy patients with pancreatic cancer who underwent TOMO were enrolled in this prospective study from February 2015 to May 2020. The clinical and dose-volume histogram parameters of the patients were collected. The optimal dose parameters for gastrointestinal radiation ulcers were confirmed based on the receiver operating characteristic curve (ROC) and the area below the ROC curve. Acute gastrointestinal tract toxic and side effect and injury grading correlation analyzed by Kruskal-Wallis rank sum test. Gastrointestinal injury often occurs during radiotherapy for pancreatic cancer, as observed using gastroscopy. The main adverse reactions were radioactive gastrointestinal inflammation (58.5%), radioactive gastrointestinal ulcers (41.4%), active bleeding (10%), newly-developed gastric retention (8.6%), and gastric varices (5.7%). As for the stomach, Dmean and V10 were related to radiation ulcer injury. ROC curve indicated that for stomach a Dmean of 13.39 Gy (area under ROC curves = 0.74, P = .048) and a V10 of 72.21% (area = 0.74, P = .048) was the tolerated dose for the injury of stomach radiation ulcer. As for duodenum, aV20 and aV25 are related to radiation ulcer injury. ROC curve indicated that aV20 of 22.82 cm3 (area = 0.68, P = .025) and aV25 of 32.04 cm3 (area = 0.66, P < .047) was the tolerated dose for the injury of duodenum radiation ulcer. The acute gastrointestinal tract toxic and side effects have no significant correlation with injury grading under gastroscope. Dmean > 13.39 Gy and V10 > 72.21% were the key dosimetric indices for predicting radiation-induced gastric ulcer, and aV20 > 22.82 cm3 and aV25 > 32.04 cm3 were for duodenal. Gastrointestinal reactions cannot be used as an overall basis for the diagnosis of gastrointestinal injury, and gastroscopy is recommended as a review item after radiotherapy.

OBJECTIVE: We report a dosimetric study in whole breast irradiation (WBI) of plan robustness evaluation against position error with two radiation techniques: tangential intensity-modulated radiotherapy (T-IMRT) and multi-angle IMRT (M-IMRT).
METHODS: Ten left-sided patients underwent WBI were selected. The dosimetric characteristics, biological evaluation and plan robustness were evaluated. The plan robustness quantification was performed by calculating the dose differences (Δ) of the original plan and perturbed plans, which were recalculated by introducing a 3-, 5-, and 10-mm shift in 18 directions.
RESULTS: M-IMRT showed better sparing of high-dose volume of organs at risk (OARs), but performed a larger low-dose irradiation volume of normal tissue. The greater shift worsened plan robustness. For a 10-mm perturbation, greater dose differences were observed in T-IMRT plans in nearly all directions, with higher ΔD98%, ΔD95%, and ΔDmean of CTV Boost and CTV. A 10-mm shift in inferior (I) direction induced CTV Boost in T-IMRT plans a 1.1 (ΔD98%), 1.1 (ΔD95%), and 1.7 (ΔDmean) times dose differences greater than dose differences in M-IMRT plans. For CTV Boost, shifts in the right (R) and I directions generated greater dose differences in T-IMRT plans, while shifts in left (L) and superior (S) directions generated larger dose differences in M-IMRT plans. For CTV, T-IMRT plans showed higher sensitivity to a shift in the R direction. M-IMRT plans showed higher sensitivity to shifts in L, S, and I directions. For OARs, negligible dose differences were found in V20 of the lungs and heart. Greater ΔDmax of the left anterior descending artery (LAD) was seen in M-IMRT plans.
CONCLUSIONS: We proposed a plan robustness evaluation method to determine the beam angle against position uncertainty accompanied by optimal dose distribution and OAR sparing.

Objective. To quantitatively investigate the impact of spot position error (PE) on the dose distribution in (Spot-scanning arc therapy) SPArc plans compared to Intensity-Modulated Proton Therapy (IMPT).Approach.Twelve representative cases, including brain, lung, liver, and prostate cancers, were retrospectively selected. Spot PEs were simulated during dynamic SPArc treatment delivery. Two types of errors were generated, including random error and systematic error. Two different probability distributions of random errors were used (1) Gaussian distribution (PEran-GS) (2) uniform distribution (PEran-UN). In PEran-UN, four sub-scenarios were considered: 25%, 50%, 75%, and 100% spots were randomly selected in various directions on the scale of 0-1 mm or 0-2 mm of PE. Additionally, systematic error was simulated by shifting all the spot uniformly by 1 or 2 mm in various directions (PEsys). Gamma-index Passing Rate (GPR) is applied to assess the dosimetric perturbation quantitatively.Main results.For PEran-GSin the 1 mm scenario, both SPArc and IMPT are comparable with a GPR exceeding 99%. However, for PEran-GSin 2 mm scenario, SPArc could provide better GPR. As PEsysof 2 mm, SPArc plans have a much better GPR compared to IMPT plans: SPArc\'s GPR is 99.59 ± 0.47%, 93.82 ± 4.07% and 64.58 ± 15.83% for 3 mm/3%, 2 mm/2% and 1 mm/1% criteria compared to IMPT with 97.49 ± 2.44%, 84.59 ± 4.99% and 42.02 ± 6.31%.Significance.Compared to IMPT, SPArc shows better dosimetric robustness in spot PEs. This study presents the first simulation results and the methodology that serves as a reference to guide future investigations into the accuracy and quality assurance of SPArc treatment delivery.

Objective.In proton pencil beam scanning (PBS) continuous delivery, the beam is continuously delivered without interruptions between spots. For synchrotron-based systems, the extracted beam current exhibits a spill structure, and recent publications on beam current measurements have demonstrated significant fluctuations around the nominal values. These fluctuations potentially lead to dose deviations from those calculated assuming a stable beam current. This study investigated the dosimetric implications of such beam current fluctuations during proton PBS continuous scanning.Approach.Using representative clinical proton PBS plans, we performed simulations to mimic a worst-case clinical delivery environment with beam current varies from 50% to 250% of the nominal values. The simulations used the beam delivery parameters optimized for the best beam delivery efficiency of the upcoming particle therapy system at Mayo Clinic Florida. We reconstructed the simulated delivered dose distributions and evaluated the dosimetric impact of beam current fluctuations.Main results.Despite significant beam current fluctuations resulting in deviations at each spot level, the overall dose distributions were nearly identical to those assuming a stable beam current. The 1 mm/1% Gamma passing rate was 100% for all plans. Less than 0.2% root mean square error was observed in the planning target volume dose-volume histogram. Minimal differences were observed in all dosimetric evaluation metrics.Significance.Our findings demonstrate that with our beam delivery system and clinical planning practice, while significant beam current fluctuations may result in large local move monitor unit deviations at each spot level, the overall impact on the dose distribution is minimal.

BACKGROUND: To integrate radiomics and dosiomics features from multiple regions in the radiation pneumonia (RP grade ≥ 2) prediction for esophageal cancer (EC) patients underwent radiotherapy (RT).
METHODS: Total of 143 EC patients in the authors\' hospital (training and internal validation: 70%:30%) and 32 EC patients from another hospital (external validation) underwent RT from 2015 to 2022 were retrospectively reviewed and analyzed. Patients were dichotomized as positive (RP+) or negative (RP-) according to CTCAE V5.0. Models with radiomics and dosiomics features extracted from single region of interest (ROI), multiple ROIs and combined models were constructed and evaluated. A nomogram integrating radiomics score (Rad_score), dosiomics score (Dos_score), clinical factors, dose-volume histogram (DVH) factors, and mean lung dose (MLD) was also constructed and validated.
RESULTS: Models with Rad_score_Lung&Overlap and Dos_score_Lung&Overlap achieved a better area under curve (AUC) of 0.818 and 0.844 in the external validation in comparison with radiomics and dosiomics models with features extracted from single ROI. Combining four radiomics and dosiomics models using support vector machine (SVM) improved the AUC to 0.854 in the external validation. Nomogram integrating Rad_score, and Dos_score with clinical factors, DVH factors, and MLD further improved the RP prediction AUC to 0.937 and 0.912 in the internal and external validation, respectively.
CONCLUSIONS: CT-based RP prediction model integrating radiomics and dosiomics features from multiple ROIs outperformed those with features from a single ROI with increased reliability for EC patients who underwent RT.