Effects of electron density force to 1.0 and fill to 1.0 on VMAT treatment plans for lung SBRT.

PURPOSE: The aim of this study is to determine the effect of forcing and filling the electron density (ED) to 1.0 of the planning target volume (PTV) overdose distribution in lung SBRT treatment leading to shortening patient treatment time and increasing patient comfort by reducing MU/fraction due to ED manipulation effect. METHODS: In this study, 36 lung SBRT plans of 12 suitable patients who prescribed a total dose of 50 Gy in five fractions were generated with Monaco v.5.10 TPS using the Monte Carlo (MC) algorithm and volumetric modulated arc therapy (VMAT) technique by PTV ED values forcing as well as filling to 1.0 and comparatively assessed. The first group of plans was created by using the patient's original ED, second and third groups of plans were reoptimized by forcing and filling the ED of PTV to 1.0, respectively, therefore acquiring a new dose distribution which lead to comparatively assessment the effects of changes in ED on PTV and OAR doses. RESULTS: Assessment of treatment plans revealed that mean MU/fx numbers were decreased by 76% and 75.25% between Groups 1 and 2, Groups 1 and 3, respectively. The number of segments was also reduced in Group 1 by up to 15% compared with Groups 2 and 3. Maximum HI and CI differences for PTV between Groups 1 and 2 were less than 1% and Groups 1 and 3 were 1.5% which indicates all 3 group plans were comparable in terms of dose distribution within PTV. CONCLUSIONS: Forcing and filling the ED of PTV to 1.0 strategy has provided reduced a number of segments and MU/fx without a significant change in PTV mean and maximum doses, thereby decreasing treatment time and patient discomfort during treatment. This process should be considered in line of a potential number of patients as well as prescribed dose and MU/fx numbers.

In Silico Comparison of Three Different Beam Arrangements for Intensity-Modulated Proton Therapy for Postoperative Whole Pelvic Irradiation of Prostate Cancer.

Background and purpose: Proton therapy has been shown to provide dosimetric benefits in comparison with IMRT when treating prostate cancer with whole pelvis radiation; however, the optimal proton beam arrangement has yet to be established. The aim of this study was to evaluate three different intensity-modulated proton therapy (IMPT) beam arrangements when treating the prostate bed and pelvis in the postoperative setting. Materials and Methods: Twenty-three post-prostatectomy patients were planned using three different beam arrangements: two-field (IMPT2B) (opposed laterals), three-field (IMPT3B) (opposed laterals inferiorly matched to a posterior-anterior beam superiorly), and four-field (IMPT4B) (opposed laterals inferiorly matched to two posterior oblique beams superiorly) arrangements. The prescription was 50 Gy radiobiological equivalent (GyE) to the pelvis and 70 GyE to the prostate bed. Comparisons were made using paired two-sided Wilcoxon signed-rank tests. Results: CTV coverages were met for all IMPT plans, with 99% of CTVs receiving ≥ 100% of prescription doses. All organ at risk (OAR) objectives were met with IMPT3B and IMPT4B plans, while several rectum objectives were exceeded by IMPT2B plans. IMPT4B provided the lowest doses to OARs for the majority of analyzed outcomes, with significantly lower doses than IMPT2B +/- IMPT3B for bladder V30-V50 and mean dose; bowel V15-V45 and mean dose; sigmoid maximum dose; rectum V40-V72.1, maximum dose, and mean dose; femoral head V37-40 and maximum dose; bone V40 and mean dose; penile bulb mean dose; and skin maximum dose. Conclusion: This study is the first to compare proton beam arrangements when treating the prostate bed and pelvis. four-field plans provided better sparing of the bladder, bowel, and rectum than 2- and three-field plans. The data presented herein may help inform the future delivery of whole pelvis IMPT for prostate cancer.

A photoelectrochemical sensor based on In2S3/AgInS2 in situ Z-type heterojunction with "photo-modulated interface charge" for sensitive detection of Programmed Death-Ligand 1.

The construction of heterostructure photoelectrodes can enhance the performance of photoelectrochemical (PEC) sensors. However, it is still a critical challenge to achieve efficient transfer of interface carriers. In this paper, we propose a strategy of "photo-modulated interface charge" to design a PEC sensor based on a hollow hexagonal tubular In2S3/AgInS2 in situ Z-type heterojunction for the susceptible detection of Programmed Death-ligand 1 (PD-L1). The hollow structured In2S3/AgInS2 is ingeniously synthesized employing indium-sourced MIL-68 as a sacrificial template and in situ cation exchange technique. This composite material has close contact interfaces due to in situ growth, which facilitates the spontaneous establishment of a robust and stable built-in electric field between the interfaces. Moreover, the inner cavity structure promotes multiple light refractions and scatterings, significantly enhancing light trapping capability. Under the influence of both light irradiation and electric field force, the migration direction of the interfacial charge is reversed, forming a Z-transfer path, which effectively delays the compounding of the electron-hole pairs (e-/h+) and further improves the sensitivity of the sensor. The minimum detection threshold of the PEC sensor is 26.58 fg/mL, and the feasibility of real samples is investigated, providing new insights for early diagnosis and prognostic treatment of diseases.

Setup errors analysis in iterative kV CBCT: A clinical study of cervical cancer treated with Volumetric Modulated Arc Therapy.

OBJECTIVE: This study aims to analyze setup errors in pelvic Volumetric Modulated Arc Therapy (VMAT) for patients with non-surgical primary cervical cancer, utilizing the onboard iterative kV cone beam CT (iCBCT) imaging system on the Varian Halcyon 2.0 ring gantry structure accelerator to enhance radiotherapy precision. METHOD: We selected 132 cervical cancer patients who underwent VMAT with daily iCBCT imaging guidance. Before each treatment session, a registration method based on the bony structure was employed to acquire iCBCT images with the corresponding planning CT images. Following verification and adjustment of image registration results along the three axes (but not rotational), setup errors in the lateral (X-axis), longitudinal (Y-axis), and vertical (Z-axis) directions were recorded for each patient. Subsequently, we analyzed 3642 iCBCT image setup errors. RESULTS: The mean setup errors for the X, Y, and Z axes were 4.50 ± 3.79 mm, 6.08 ± 6.30 mm, and 1.48 ± 2.23 mm, respectively. Before correction with iCBCT, setup margins based on the Van Herk formula for the X, Y, and Z axes were 6.28, 12.52, and 3.26 mm, respectively. In individuals aged 60 years and older, setup errors in the X and Y axes were significantly larger than those in the younger group (p < 0.05). Additionally, there is no significant linear correlation between setup errors and treatment fraction numbers. CONCLUSION: Data analysis underscores the importance of precise Y-axis setup for cervical cancer patients undergoing VMAT. Radiotherapy centers without daily iCBCT should appropriately extend the planning target volume (PTV) along the Y-axis for cervical cancer patients receiving pelvic VMAT. Elderly patients exhibit significantly larger setup errors compared to younger counterparts. In conclusion, iCBCT-guided radiotherapy is recommended for cervical cancer patients undergoing VMAT to improve setup precision.

Dosimetric Study and Robustness Analysis of Base Note Intensive Locked Field Radiotherapy for Left Breast Cancer.

Background: The locked vision plan can make the left breast cancer heart and lung organs dose. Objective: The aim of the present study was to compare the dosimetric differences between field-locked and field-split plans in intensity-modulated radiotherapy for left-sided breast cancer, to explore the effect of field-locking on the low-dose region, and to evaluate its robustness to the radiotherapy target, in order to provide a reference for the selection of clinical radiotherapy protocols. Methods: A total of 30 patients were selected after radical left breast cancer surgery, and 7-field locked-field and split-field plans were developed to compare the dose difference (∆D) between the target area and each organ at risk, and to introduce offsets of 3, 5 and 7 mm in six directions and recalculate the perturbed dose distributions, and to compare the ∆D between the original and the perturbed plans according to the robustness of the plans. Results: The results revealed that the D98%, D95% and Dmean values of the planning target volume (PTV) of the two plans differed little and were not statistically different. The locked field plan provided better protection for the left lung, right lung, heart, right breast and left anterior descending coronary artery. For PTV∆D98%, PTV∆D95%, PTV∆Dmean, the ∆D was higher for the Locked Fields plan, and for LungL∆5, LungL∆20 and Heart∆mean, the ∆D was higher for the original plan. Discussion: It was concluded that the field-locking plan could reduce the low-dose area of the affected lung and provide improved protection to the remaining critical organs, and the field-locking plan was more robust in protecting critical organs. Meanwhile, the field-locking plan showed higher sensitivity to positional deviation for target PTV.

Dosimetric effect of collimator rotation on intensity modulated radiotherapy and volumetric modulated arc therapy for rectal cancer radiotherapy.

INTRODUCTION: Intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) are the main radiotherapy techniques for treating and managing rectal cancer. Collimator rotation is one of the crucial parameters in radiotherapy planning, and its alteration can cause dosimetric variations. This study assessed the effect of collimator rotation on the dosimetric results of various IMRT and VMAT plans for rectal cancer. MATERIALS AND METHODS: Computed tomography (CT) images of 20 male patients with rectal cancer were utilized for IMRT and VMAT treatment planning with various collimator angles. Nine different IMRT techniques (5, 7, and 9 coplanar fields with collimator angles of 0°, 45°, and 90°) and six different VMAT techniques (1 and 2 full coplanar arcs with collimator angles of 0°, 45°, and 90°) were planned for each patient. The dosimetric results of various treatment techniques for target tissue (conformity index [CI] and homogeneity index [HI]) and organs at risk (OARs) sparing (parameters obtained from OARs dose-volume histograms [DVH]) as well as radiobiological findings were analyzed and compared. RESULTS: The 7-fields IMRT technique demonstrated lower bladder doses (V40Gy, V45Gy), unaffected by collimator rotation. The 9-fields IMRT and 2-arcs VMAT (excluding the 90-degree collimator) had the lowest V35Gy and V45Gy. A 90-degree collimator rotation in 2-arcs VMAT significantly increased small bowel and bladder V45Gy, femoral head doses, and HI values. Radiobiologically, the 90-degree rotation had adverse effects on small bowel NTCP (normal tissue complication probability). No superiority was found for a 45-degree collimator rotation over 0 or 30 degrees in VMAT techniques. CONCLUSION: Collimator rotation had minimal impact on dosimetric parameters in IMRT planning but is significant in VMAT techniques. A 90-degree rotation in VMAT, particularly in a 2-full arc technique, adversely affects PTV homogeneity index, bladder dose, and small bowel NTCP. Other evaluated collimator angles did not significantly affect VMAT dosimetrical or radiobiological outcomes.

Proton Therapy Reduces the Effective Dose to Immune Cells in Mediastinal Hodgkin Lymphoma Patients.

Purpose: Effective dose to circulating immune cells (EDIC) is associated with survival in lung and esophageal cancer patients. This study aimed to evaluate the benefit of intensity-modulated proton therapy (IMPT) for EDIC reduction compared with volumetric modulated arc therapy (VMAT) in mediastinal Hodgkin lymphoma (mHL) patients. Materials and Methods: Ten consecutive mHL patients treated with involved-site IMPT after frontline chemotherapy were included. The mean dose to the heart, lung, and liver and the integral dose to the body were obtained, and we calculated EDIC based on these variables. The effective dose to circulating immune cells was compared between IMPT and VMAT schedules. Results: The median EDIC was reduced from 1.93 Gy (range: 1.31-3.87) with VMAT to 1.08 Gy (0.53-2.09) with IMPT (P < .01). Integral dose reduction was the main driver of EDIC reduction with IMPT, followed by lung sparing. Conclusion: Intensity-modulated proton therapy significantly reduced EDIC in mHL patients undergoing consolidation involved-site radiation therapy. Integral dose reduction combined with improved lung sparing was the main driver of EDIC reduction with IMPT.

A retrospective study on the effectiveness of intensity modulated radiation therapy for thyroid associated ophthalmopathy at a single institute.

Thyroid-associated ophthalmopathy (TAO) is a hallmark autoimmune condition, and the treatment of TAO requires a multidisciplinary approach. Radiation therapy (RT) is a viable treatment option for active TAO, IMRT is a more precise technology in radiation oncology. This study aims to evaluate the efficacy, feasibility, and safety of orbital intensity-modulated radiation therapy (IMRT) in the treatment of TAO. A single-center retrospective analysis was conducted, including patients diagnosed with moderate to severe active TAO at the Department of Radiation Oncology, Peking University Third Hospital, from October 2020 to October 2023, who had poor responses to corticosteroid treatment. These patients subsequently received IMRT treatment, followed by a period of follow-up and retrospective analysis. The study focused on the outcomes of treatment efficacy, safety, and acute toxic reactions induced by radiation therapy. Improvements in clinical activity score (CAS) at 4 and 12 months were considered as primary and secondary study endpoints, respectively, along with the incidence rate of adverse events. The median follow-up period was 12 months. The median follow-up time after radiation therapy was 12 months. There was no statistically significant difference in CAS between before and 4 months after radiation therapy (CAS: 5.53 ± 2.07 vs.4.68 ± 2.62; R squared: 0.21; 95% CI: - 1.01-0.02; P = 0.054). However, there was a significant reduction in CAS 12 months post-treatment compared to pre-treatment (CAS: 5.53 ± 2.07 vs. 3.06 ± 2.38; R squared: 0.66; 95% CI: 3.42 - 1.52; P < 0.001). The CAS showed a progressively decreasing trend at both 4 months and 12 months post-treatment. In the combined radiotherapy with glucocorticoid treatment group, a statistically significant difference was found between the CAS before treatment and 12 months after radiotherapy (CAS: 6.38 ± 2.00 vs. 3.88 ± 2.85; R squared: 0.66; 95% CI - 4.11 to 0.89; P = 0.008). In the radiotherapy alone group, a statistically significant difference was found between the CAS before treatment and 12 months after radiotherapy (CAS: 4.78 ± 1.92 vs. 2.33 ± 1.73; R squared: 0.66; 95% CI - 3.89 to 1.00; P = 0.005). A few patients experienced Grade I periorbital edema, conjunctival congestion, and dry eye syndrome, but no adverse events such as cataracts, radiation retinopathy, or radiation-induced optic neuropathy were observed by the end of the follow-up period. Orbital IMRT is an effective treatment modality for moderate to severe active TAO, demonstrating significant efficacy even in patients who had not achieved success with previous treatments such as corticosteroids. This retrospective study was approved by the Ethics Committee of Peking University Third Hospital. The permit number was M2024220 and data of registration was April I, 2024.

Failure patterns and individualized treatment plans of reirradiation for inoperable locally recurrent nasopharyngeal carcinoma.

Re-irradiation with intensity-modulated radiotherapy (IMRT) remains the primary treatment modality for inoperable locally recurrent nasopharyngeal carcinoma (NPC). However, the rate of radiation-related late adverse effects is often substantially high. Therefore, we aimed to explore failure patterns and individualized treatment plans of re-irradiation for inoperable locally recurrent NPC. Ninety-seven patients who underwent IMRT were retrospectively analyzed. Sixty-two patients had clinical target volume of recurrence (rCTV) delineated, and thirty-five patients had only gross tumor volume of recurrence (rGTV) delineated. Twenty-nine patients developed second local failures after re-irradiation with IMRT (28 cases available). Among those patients, 64.3% (18/28) of patients and 35.7% (10/28) developed in-field or out-field, respectively. No statistical correlation was observed between target volume (rGTV or rCTV) and the local recurrence rate, local failure patterns, grade ≥ 3 toxicity, and survival. Multivariate analysis showed that recurrent T (rT) stage (HR 2.62, P = 0.019) and rGTV volume (HR 1.73, P = 0.037) were independent prognostic factors for overall survival (OS). Risk stratification based on rT stage and rGTV volume revealed that low risk group had a longer 3-year OS rate (66.7% vs. 23.4%), lower total grade ≥ 3 toxicity (P = 0.004), and lower re-radiation associated mortality rates (HR 0.45, P = 0.03) than high risk group. This study demonstrates that the delineation of rCTV may not be beneficial for re-irradiation using IMRT in locally recurrent NPC. Patients with low risk were most suitable for re-irradiation, with maximizing local salvage and minimizing radiation-related toxicities. More precise and individualized plans of re-irradiation are warranted.

Treatment of Stages I-III Squamous Cell Anal Cancer: A Comparative Effectiveness Systematic Review.

PURPOSE: To assess the effectiveness and harms of initial treatment strategies for stages I-III anal squamous cell cancer (SCC). METHODS: We searched Medline®, Embase®, and CENTRAL®, between January 1, 2000- March 2024, for randomized controlled trials and nonrandomized studies of interventions comparing initial treatment strategies. Individual study risk of bias (RoB) and overall strength of evidence (SOE) were evaluated for a prespecified outcome list using standardized methods. RESULTS: We identified 33 eligible studies and extracted data. Six were deemed low/moderate RoB. Compared with radiotherapy (RT) alone, chemoradiotherapy (CRT) with 5-fluorouracil (FU) and mitomycin C (MMC) probably shows a benefit in locoregional failure (LRF), disease-specific (DSS), and colostomy-free survival (CFS) (moderate SOE) yet may result in greater overall and acute hematologic toxicity, with no difference in late harms (low SOE). CRT with 5FU+MMC may show a benefit in LRF, DSS, and CFS rates compared with 5FU alone (low SOE). CRT with 5FU+cisplatin vs 5FU+MMC probably results in no differences in several effectiveness outcomes or overall acute or late harms, and probably increases hematologic toxicity with MMC (moderate SOE). Compared with CRT using capecitabine+MMC, CRT with capecitabine+MMC+paclitaxel may improve OS, DSS, and CFS, yet cause more acute harms (low SOE). Evidence was insufficient for remaining comparisons. CONCLUSIONS: CRT with 5FU+MMC or 5FU+cisplatin is likely more effective yet incurs greater acute hematologic toxicity than RT alone or single-agent CRT. Adding paclitaxel to capecitabine+MMC may increase treatment efficacy and toxicity. Evidence is insufficient comparing post-treatment surveillance strategies and patient-reported outcomes, highlighting research opportunities.

Sidelobes and sideband minimization in time-modulated array antenna based on chaotic exchange nonlinear dandelion optimization algorithm.

Time-modulated array antenna (TMAA) is a new type of array antenna based on time modulation technology. By introducing "time" as the fourth dimensional design freedom into the design of conventional array antennas in three-dimensional space, the array antenna has time modulation characteristics, which better controls the radiation characteristics of the array antenna and achieves the best far-field radiation pattern synthesis. This paper designs a Time-modulated linear array (TMLA) with low sidelobe level (SLL) and low sideband level (SBL) based on the chaotic exchange nonlinear dandelion optimization (CENDO) algorithm. Three optimization methods are studied: firstly, determining the optimal on-time (τnn) for each array element; The second is to determine the optimal on-time (τnn) and optimal uniform array element spacing (d) for each array element; The third is to determine the optimal opening time (ton), closing time (toff), and optimal uniform array element spacing (d) for each array element. To achieve simultaneous reduction of sidelobe level and suppression of harmonic interference. The same array model contains different harmonic frequency radiation. In this article, we only considered two harmonic frequencies, namely the first sideband frequency and the second sideband frequency. Because the harmonic of other sideband frequencies has a very small impact on the radiation of the fundamental wave, it can be ignored. To demonstrate the stronger ability of the CENDO algorithm in optimizing Time-modulated array antennas, and in line with the principle of fairness and impartiality, this paper also simulates different Time-modulated array models and compares the results of the CENDO algorithm with other published literature. It is concluded that this study shows lower SLL and lower SBL in different models. This provides a more scientific and accurate explanation of the superiority of the CENDO algorithm compared to other algorithms in the field of antenna optimization in electromagnetics. At the same time, this also provides great research value and fundamental support for designing high-performance Time-modulated array antennas in subsequent engineering applications.

Can titanium surface technology reduce cost for biologics in anterior lumbar interbody fusion?

OBJECTIVE: Advances in surface architecture and technology have made interbody fusion devices more bioactive, with the hope of facilitating the fusion process more successfully. The advent of these increasingly bioactive implants may reduce reliance on more expensive biologics that have previously been used to achieve high fusion rates. METHODS: A retrospective review of prospectively collected data (August 2018-December 2019) was conducted of consecutively performed anterior lumbar interbody fusions in which an acid-etched, nanosurface-modulated, titanium interbody device packed only with corticocancellous allograft chips and local blood was used. Minimum follow-up was 1 year, and inclusion required available imaging and outcome metrics preoperatively and at 1 year. Fusion and subsidence were assessed via CT scans and/or dynamic radiographs. Health-related quality-of-life measures (Oswestry Disability Index [ODI], visual analog scale [VAS] back/leg) were collected pre- and postoperatively. RESULTS: In total, 55 patients met inclusion criteria (1 year of follow-up, available imaging, and outcome metrics). A total of 69 lumbar levels were treated in these 55 patients. The mean age was 67 ± 12.1 years, with 47% female patients. Roughly one-third (35%) had previous spine surgery, and approximately one-tenth (9.1%) had prior spinal fusion. A total of 20.6% were treated at multiple levels (mean levels per patient 1.2, minimum 1, maximum 3). The mean preoperative patient-reported outcomes were as follows: ODI 39.71 ± 18.15, VAS back 6.49 ± 2.19, and VAS leg 5.41 ± 2.71. One year after surgery, the mean improvements in patient-reported outcomes (vs preoperative scores) were as follows: ODI -22.9 ± 13.08 (p < 0.001), VAS back -3.75 ± 2.03 (p < 0.001), VAS leg -3.73 ± 2.32 (p < 0.001). All levels achieved fusion at 1 year postoperatively based on CT scans (65/69 levels) or dynamic radiographs (4/69 levels, change in score < 5% on flexion-extension radiographs). Four of the 65 levels were assigned to the grade 3 category according to a CT-based grading system, meaning cranial and caudal endplate bone apposition to the implant on both surfaces with no clear intervertebral bone connection through or around the implant. Sixty-one of 65 were found to have contiguous intervertebral bone bridging and thus were assigned to grade 1 (n = 54) or grade 2 (n = 7). Low-grade graft subsidence (Marchi grade 0 or I) occurred in 9 levels (13.0%) and high-grade subsidence (Marchi grade II or III) in 4 levels (5.8%). No patients required reoperation at the level of anterior lumbar interbody fusion and no radiographic or clinical evidence of pedicle screw loosening or failure was observed. CONCLUSIONS: The combination of advances in materials science and surface technology as demonstrated with a nanotechnology titanium cage resulted in the ability to obtain lumbar interbody fusion with allograft chips and local blood alone. Achieving high fusion rates with low-cost biologics/allograft provides for an attractive pathway toward reducing the cost of reconstructive spine care, and a potential incremental benefit for healthcare economics.

Superficial Dosimetry Study of the Frequency of Bolus Using in Volumetric Modulated Arc Therapy after Modified Radical Mastectomy.

OBJECTIVE: To investigate the effect of various frequencies of bolus use on the superficial dose of volumetric modulated arc therapy after modified radical mastectomy for breast cancer. METHODS: Based on the computed tomography images of a female anthropomorphic breast phantom, a 0.5 cm silicone-based 3D-printed bolus was created. Nine points evenly distributed on the breast skin were selected for assessing the skin dose, and a volume of subcutaneous lymphatic drainage of the breast (noted as ROI2-3) was delineated for assessing the chest wall dose. The treatment plans with and without bolus (plan_wb and plan_nb) were separately designed using the prescription of 50 Gy in 25 fractions following the standard dose constraints of the adjacent organ at risk. To characterize the accuracy of treatment planning system (TPS) dose calculations, the doses of the nine points were measured five times by thermoluminescence dosimeters (TLDs) and then were compared with the TPS calculated dose. RESULTS: Compared with Plan_nb (144.46 ± 10.32 cGy), the breast skin dose for plan_wb (208.75 ± 4.55 cGy) was significantly increased (t = -18.56, P < 0.001). The deviation of skin dose was smaller for Plan_wb, and the uniformity was significantly improved. The calculated value of TPS was in good agreement with the measured value of TLD, and the maximum deviation was within 5%. Skin and ROI2-3 doses were significantly increased with increasing frequencies of bolus applications. The mean dose of the breast skin and ROI2-3 for 15 and 23 times bolus applications were 45.33 Gy, 50.88 Gy and 50.36 Gy, 52.39 Gy, respectively. CONCLUSION: 3D printing bolus can improve the radiation dose and the accuracy of the planned dose. Setting Plan_wb to 15 times for T1-3N+ breast cancer patients and 23 times for T4N+ breast cancer patients can meet the clinical need. Quantitative analysis of the bolus application frequency for different tumor stages can provide a reference for clinical practice.

Applying mixed-integer linear programming to the non-coplanar beam angle optimization of intensity-modulated radiotherapy for liver cancer.

Background: Currently, intensity-modulated radiation therapy (IMRT) is commonly used in radiotherapy clinics. However, designing a treatment plan with multiple beam angles depends on the experience of human planners, and is mostly achieved using a trial-and-error approach. It is preferrable but challenging to solve this issue automatically and mathematically using an optimization approach. The goal of this study is to develop a mixed-integer linear programming (MILP) approach for the beam angle optimization (BAO) of non-coplanar IMRT for liver cancer. Methods: MILP models for the BAO of both coplanar and non-coplanar IMRT treatment plans were developed. The beam angles of the IMRT plans were first selected by the MILP model built using mathematical optimization software. Next, the IMRT plans with the selected beam angles was created in a commercial treatment planning system. Finally, the fluence map and dose distribution of the IMRT plans were generated under pre-defined dose-volume constraints. The IMRT plans of 10 liver cancer patients previously treated at our institute were used to assessed the proposed MILP models. For each patient, both coplanar and non-coplanar IMRT plans with beam angles optimized by the MILP models were compared with the IMRT plan clinically approved by physicians. Results: The MILP model-guided IMRT plans showed reduced doses for most of the organs at risk (OARs). Compared with the IMRT plans clinically approved by physicians, the doses for the spinal cord (28.5 vs. 36.1, P=0.001<0.05) and liver (27.6 vs. 29.1, P=0.005<0.05) decreased significantly in the IMRT plans with non-coplanar beams selected by the MILP models. Conclusions: The MILP model is an effective tool for the BAO in coplanar and non-coplanar IMRT treatment planning. It facilitates the automation of IMRT treatment planning for current high-precision radiotherapy.

Incidence and risk factors associated with the development of hypothyroidism after postoperative chemoradiotherapy for head and neck cancer patients with high-risk features: Supplementary analysis of JCOG1008.

BACKGROUND AND PURPOSE: Hypothyroidism is a recognized late adverse event following radiotherapy for head and neck cancer (HNC). In the JCOG1008 trial, we treated patients with high-risk HNC with postoperative chemoradiotherapy. We aimed to elucidate factors associated with hypothyroidism by analyzing the JCOG1008 data. MATERIALS AND METHODS: In 2012-2018, 261 patients from 28 institutions were enrolled in JCOG1008. Thyroid function tests were conducted to assess hypothyroidism, including free thyroxine (FT4) and thyroid-stimulating hormone assays. Hypothyroidism was defined as Grade 2 or higher in CTCAE v4.0. Various clinical and dosimetric parameters were analyzed. In radiotherapy, there were no dose constraints for the thyroid. Multivariable analysis was conducted on these variables to identify predictive factors for hypothyroidism. RESULTS: The analysis included 162 patients (57 with 3D-CRT and 105 with IMRT), with a median follow-up of 4.7 years (0.3-9.3 years). Among these, 27 (16.7 %) developed hypothyroidism within 2 years after radiotherapy. In a multivariable analysis, the weekly cisplatin [OR=7.700 (CI: 1.632-36.343, p = 0.010)] and baseline FT4 [OR=0.009 (CI: <0.001-0.313, p = 0.010)] were significantly associated with hypothyroidism in the IMRT group. Regarding dosimetric characteristics, V60Gy [OR=1.069 (CI: 0.999-1.143, p = 0.054)] was potentially associated with the development of hypothyroidism. CONCLUSION: The study revealed that the incidence of hypothyroidism within 2 years after postoperative chemoradiotherapy for high-risk HNC was 16.7 % based on analytical results from prospective clinical trials.

Compliant Lattice Modulations Enable Anomalous Elasticity in Ni-Mn-Ga Martensite.

High mobility of twin boundaries in modulated martensites of Ni-Mn-Ga-based ferromagnetic shape memory alloys holds a promise for unique magnetomechanical applications. This feature has not been fully understood so far, and in particular, it has yet not been unveiled what makes the lattice mechanics of modulated Ni-Mn-Ga specifically different from other martensitic alloys. Here, results of dedicated laser-ultrasonic measurements on hierarchically twinned five-layer modulated (10M) crystals fill this gap. Using a combination of transient grating spectroscopy and laser-based resonant ultrasound spectroscopy, it is confirmed that there is a shear elastic instability in the lattice, being significantly stronger than in any other martensitic material and also than what the first-principles calculations for Ni-Mn-Ga predict. The experimental results reveal that the instability is directly related to the lattice modulations. A lattice-scale mechanism of dynamic faulting of the modulation sequence that explains this behavior is proposed; this mechanism can explain the extraordinary mobility of twin boundaries in 10M.

Evaluation of the toxicity of prophylactic extended-field radiation therapy with volumetric modulated arc therapy in combination with concomitant chemoradiotherapy in patients with locally advanced stage IIIC1r cervical cancer according to the 2018 FIGO classification.

Background: To evaluate the toxicity of prophylactic extended-field radiation therapy (EFRT) combined with volumetric modulated arc therapy (VMAT) in combination with cisplatin chemotherapy for locally advanced stage IIIC1r cervical cancer [2018 International Federation of Gynecology and Obstetrics (FIGO)]. Materials and methods: Thirty patients with stage IIIC1r cervical cancer were treated with EFRT combined with concurrent cisplatin. Acute toxicities were evaluated according to the common terminology criteria for adverse events (CTCAE v.5). Delayed toxicities were evaluated according to the classification criteria of radiation damage toxicity of the Radiation Therapy Oncology Group (RTOG). The efficacy of the regimens was evaluated using response evaluation criteria in solid tumors (RECIST v1.1). Spearman correlation was used to analyze the correlation between acute gastrointestinal toxicity (nausea) and the small bowel V45. Predictive value analysis was performed using a receiver operating characteristic (ROC) curve. Results: There were no grade ≥ 3 acute toxicities. The most common acute toxicity observed was nausea (grade 2 in 40%), which was positively correlated with the volume of the small intestine receiving 45 Gy. When the V45 of the small intestine was > 83.2 cc, the risk of grade 2 acute upper digestive tract toxicity (nausea) increased. The major late toxicities had the following distributions: Grade 1 diarrhea, 36.7%; Grade 1 abdominal pain, 13.3%; and Grade 1 radiation cystitis. No grade ≥ 2 late toxicities were observed. Conclusions: Treatment of locally advanced stage IIIC1r cervical cancer with EFRT combined with VMAT and concurrent cisplatin chemotherapy was well tolerated, and the acute toxicity profile was acceptable. Significant grade 3 acute/delayed toxicities were not observed.

Radiobiological analysis of VMAT treatment plan with flattened and flattening filter free photon beam: an EUD and TCP based comparative study.

Background: This study aimed to evaluate the dosimetric and radiobiological differences between 6MV flattened filter (FF) and flattening filter free (FFF) using volumetric modulated arc (VMAT) technique for head and neck (H&N) cancer patients. Materials and methods: Fifteen patients with H&N carcinoma were selected and treated with VMAT with FF (VMATFF) treatment plan. Retrospectively, additional VMAT treatment plans were developed using FFF beams (VMATFFF). Radiobiological parameters, such as equivalent uniform dose (EUD), tumor cure probability (TCP), and normal tissue complication probability (NTCP), were calculated using Niemierko's model for both VMATFF and VMATFFF. Correlation between dosimetric and radiobiological data were analyzed and compared. Results: The conformity index (CI) was 0.975 ± 0.014 (VMATFF) and 0.964 ± 0. 019 (VMATFFF) with p ≥ 0.05. Statistically, there was an insignificant difference in the planning target volume (PTV) results for TCP (%) values, with values of 81.20 ± 0.88% (VMATFF) and 81.01 ± 0.92 (%) (VMATFF). Similarly, there was an insignificant difference in the EUD (Gy) values, which were 71.53 ± 0.33 Gy (VMATFF) and 71.46 ± 0.34 Gy (VMATFFF). The NTCP values for the spinal cord, left parotid, and right parotid were 6.54 × 10-07%, 8.04%, and 7.69%, respectively, in the case of VMATFF. For VMATFFF, the corresponding NTCP values for the spinal cord, parotids left, and parotid right were 3.09 × 10-07%, 6.57%, and 6.73%, respectively. Conclusion: The EUD and Mean Dose to PTV were strongly correlated for VMATFFF. An increased mean dose to the PTV and greater TCP were reported for the VMATFF, which can enhance the delivery of the therapeutic dose to the target.

Current state, challenges, and future perspective of adaptive radiotherapy: A narrative review of nasopharyngeal carcinoma.

Patients with nasopharyngeal carcinoma often experience weight loss and tumor regression during the course of radiotherapy that lasts for up to 6-7 weeks. Adaptive radiotherapy is a systematic feedback control approach based on image-guided technology that adjusts these changes and optimizes the radiotherapy plans according to new imaging findings during treatment. There is growing evidence that adaptive radiotherapy can reduce side effects, improve the quality of life, and enhance disease control. However, the routine application of adaptive radiotherapy for nasopharyngeal remains relatively limited. This review discusses the necessity, clinical benefits, and limitations of adaptive radiotherapy, and presents the current state, challenges, and future perspective of adaptive radiotherapy strategies for nasopharyngeal carcinoma.