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Purpose The interplay effect between dynamic pencil proton beams and motion of the lung tumor presents a challenge in treating lung cancer patients in pencil beam scanning (PBS) proton therapy. The main purpose of the current study was to investigate the interplay effect on the volumetric repainting lung plans with beam delivery in alternating order (“down” and “up” directions), and explore the number of volumetric repaintings needed to achieve acceptable lung cancer PBS proton plan. Method The current retrospective study included ten lung cancer patients. The total dose prescription to the clinical target volume (CTV) was 70 Gy(RBE) with a fractional dose of 2 Gy(RBE). All treatment plans were robustly optimized on all ten phases in the 4DCT data set. The Monte Carlo algorithm was used for the 4D robust optimization, as well as for the final dose calculation. The interplay effect was evaluated for both the nominal (i.e., without repainting) as well as volumetric repainting plans. The interplay evaluation was carried out for each of the ten different phases as the starting phases. Several dosimetric metrics were included to evaluate the worst‐case scenario (WCS) and bandwidth based on the results obtained from treatment delivery starting in ten different breathing phases. Results The number of repaintings needed to meet the criteria 1 (CR1) of target coverage (D95% ≥ 98% and D99% ≥ 97%) ranged from 2 to 10. The number of repaintings needed to meet the CR1 of maximum dose (ΔD1% < 1.5%) ranged from 2 to 7. Similarly, the number of repaintings needed to meet CR1 of homogeneity index (ΔHI < 0.03) ranged from 3 to 10. For the target coverage region, the number of repaintings needed to meet CR1 of bandwidth (<100 cGy) ranged from 3 to 10, whereas for the high‐dose region, the number of repaintings needed to meet CR1 of bandwidth (<100 cGy) ranged from 1 to 7. Based on the overall plan evaluation criteria proposed in the current study, acceptable plans were achieved for nine patients, whereas one patient had acceptable plan with a minor deviation. Conclusion The number of repaintings required to mitigate the interplay effect in PBS lung cancer (tumor motion < 15 mm) was found to be highly patient dependent. For the volumetric repainting with an alternating order, a patient‐specific interplay evaluation strategy must be adopted. Determining the optimal number of repaintings based on the bandwidth and WCS approach could mitigate the interplay effect in PBS lung cancer treatment.

An understanding of regulating factors and early warning of Ulva prolifera biomass increase may reduce harm or prevent bloom disasters in the Yellow Sea. We investigated the minimum nutrient concentration and light-limiting depth (Z lim) for the growth of floating U. prolifera thalli. Bioavailable dissolved nitrogen (BDN) concentrations in most parts of the study area were almost always higher than the minimum N concentrations required for the growth of floating thalli, indicating no N limitation for the growth of floating thalli. However, the minimum N concentration required for the development of germlings into thalli was higher than BDN in the majority of the area north of 35° N. This indicated that germlings floating out of Subei Shoal were unable to grow into thalli because of N limitation. The minimum P concentration required for germling development was higher than the total dissolved P north of 35° N. This suggested that P limitation occurred for germlings floating out of Subei Shoal. The Z lim for the floating thalli was <0.1 m in most parts of Subei Shoal, which explained why the rapid growth of floating thalli only occurred when they floated out from the Subei Shoal. A grid pattern with the phased multiple increase in biomass per day was designed to predict the possible accumulated multiple increase in biomass (AcMp) when U. prolifera drifted northward following different trajectories. The predicted AcMp values in 2017, 2010, and 2009 were close to the ratio of the coverage area from remote sensing data. Such a grid pattern facilitates quick decisions in disaster prevention and reduction.

Purpose Precise dose delivery to the target is constrained by respiratory motion in intensity modulated proton therapy (IMPT) for lung cancer. This study aims to investigate the impact of treatment planning parameters on the lung cancer IMPT. Materials and methods 30 lung cancer patients treated at Shandong Cancer Hospital and institute were recruited in the study. A 4DCT dataset with 10 respiratory phases was reconstructed for each patient. The RayStation11B treatment planning system was used to create two-oblique-field IMPT plans. A prescription dose of 60 Gy (RBE) for 30 fractions was administered to 95% volume of the CTV. Five proton planning strategies were developed for each patient: (1) Range shifter (RS) plan: four plans were generated by varying range shifter thickness (0, 2, 3, and 5 cm) to change spot sizes; (2) Layer Spacing (LS) plan: four plans with different layer spacing (0.5, 1, 1.5 and 2 cm); (3) Spot Spacing (SS) plan: four plans with spot spacing variations (0.5, 1, 1.5 and 2 cm); (4) Repainting (RE) plan: layer repainting techniques with different numbers of repainting 1, 4 or 8 was adopted to the plan; (5) Ring plan: Dose fall-off was optimized using a ring structure around the target. 4D dynamic dose distributions (4DDDs) were calculated for plans created with various treatment planning parameters. Plan quality and dose-volume histogram (DVH) parameters for the target and organs at risk (OARs) were then analyzed. Results For the RS plan, the D 95% of CTV, V 20 and V 5 of ipsilateral lung increased as the spot size became larger. The D 2% in RS5 plan was slightly higher than in the other three groups. The D 95% and D 2% in the target decreased as the layer spacing increased. The average value for the ELS2 group was about 3.8 Gy (RBE) higher than that of the ELS0.5 group (69.7 vs. 65.9 Gy (RBE)). The values for V 20 and V 5 of lung were similar across groups. Variations in spot spacing had slightly impact on D 95% for the target and V 20 , V 5 for the ipsilateral lung. The effect on D 2% was more pronounced. The median D 95% values for the three groups gradually increased with the number of repainting. For the ipsilateral lung, the number of repainting had little impact on the doses of V 20 and V 5 . For the ring plan, the nominal group had slightly higher D 95% , V 20 , and V 5 values compared to the ring group. The D 2% in the nominal group was lower than that in the ring group, with average values of 65.8 and 67.6 Gy (RBE), respectively. Conclusion A systematic analysis was conducted in this study on the impact of spot size, LS, SS, layer repainting, and ring structure on the 4D robustness of IMPT plans for lung cancer patients. These five strategies demonstrated that beam spot size and layer spacing affected plan robustness, while spot spacing had relatively minor influence on robustness. The repainting technology can mitigate the interplay effect caused by respiratory motion. The application of ring structures affected the dose distribution of the moving target.

Propose Proton therapy of esophageal cancer is beneficial to spare normal tissue in clinical practice. However, intra-fractional and inter-fractional variance of tumor motion during treatment may compromise target coverage. The purpose of this study was to investigate the interplay effect due to intra-fractional motion and the effect of the robust optimization parameters for inter-fractional motion in the intensity modulation proton therapy (IMPT). Materials and methods This study retrospectively analyzed 42 patients with esophageal cancer treated at Shandong Cancer Hospital. The patients were divided into two groups. Twenty-one patients had a 4DCT image with 10 respiratory phases reconstructed (G intra ). In addition, twenty-one patients underwent a second 3D CT scan following the initial one (G inter ). The RayStation11B treatment planning system was used to create the IMPT plans for these two groups of patients. All patients were planned with a prescribed dose of 50.4 Gy (RBE) in 28 fractions for clinical target volume (CTV). 4D dynamic dose (4DDD) was then calculated to assess the interplay effect by considering respiratory motion and dynamic beam delivery for G intra . Seven IMPT plans with different robust optimization parameters were designed for the 21 G inter patient. The setup uncertainties were set to ± 0–6 mm for G inter . Plan quality and dose-volume histogram (DVH) parameters for the target and organs at risk (OARs) were then analyzed. Results For G intra , 4DDD was slightly perturbated compared to the nominal plan dose. The mean value of CTV D 98% of nominal dose and 4DDD were 49.9 and 49.1 Gy (RBE), respectively, and the CTV D 95% were 50.4 and 49.9 Gy (RBE), respectively. For G inter , the DVH parameters of the target area and the OARs showed a linear relationship with the corresponding robust optimization parameters in IMPT. When the robust optimization parameters were set with a larger value, the dose coverage of the target was improved. However, the dose of OARs increased at the same time. The D 98% of the target for the seven plans (setup6, setup5, setup4, setup3, setup2, setup1, setup0 plan) were 49.42 ± 0.75, 48.95 ± 1.21, 48.54 ± 1.48, 47.55 ± 2.31, 47.07 ± 2.71, 44.58 ± 4.20 and 44.02 ± 4.44 Gy(RBE), respectively. The D mean of heart were 12.18 ± 3.05, 11.28 ± 2.86, 10.90 ± 2.77, 9.76 ± 2.39, 9.73 ± 2.39, 8.33 ± 2.22 and 8.22 ± 2.20 Gy (RBE), respectively. Conclusion In this study, the differences in dose distributions between the 4DDD and nominal plans for G intra can be attributed to the interplay effects. While target coverage remained stable, variations in OAR doses should be evaluated for G intra . For G inter , smaller setup uncertainty parameters may not fully mitigate inter-fractional tumor motion, leading to greater variation in target dose and potential inadequate coverage. The linear relationship between setup uncertainty and D 98% suggested that improved setup uncertainties can enhance target coverage, while higher setup uncertainties tend to increase OARs doses, particularly to the heart and lungs.

Purpose To compare the dosimetric performances of intensity‐modulated proton therapy (IMPT) plans generated with two different beam angle configurations (the Right–Left oblique posterior beams and the Superior–Inferior oblique posterior beams) for the treatment of distal esophageal carcinoma in the presence of uncertainties and interplay effect. Methods and Materials Twenty patients’ IMPT plans were retrospectively selected, with 10 patients treated with the R‐L oblique posterior beams (Group R‐L) and the other 10 patients treated with the S‐I oblique posterior beams (Group S‐I). Patients in both groups were matched by their clinical target volumes (CTVs—high and low dose levels) and respiratory motion amplitudes. Dose‐volume‐histogram (DVH) indices were used to assess plan quality. DVH bandwidth was calculated to evaluate plan robustness. Interplay effect was quantified using four‐dimensional (4D) dynamic dose calculation with random respiratory starting phase of each fraction. Normal tissue complication probability (NTCP) for heart, liver, and lung was calculated, respectively, to estimate the clinical outcomes. Wilcoxon signed‐rank test was used for statistical comparison between the two groups. Results Compared with plans in Group R‐L, plans in Group S‐I resulted in significantly lower liver Dmean and lung V30Gy[RBE] with slightly higher but clinically acceptable spinal cord Dmax. Similar plan robustness was observed between the two groups. When interplay effect was considered, plans in Group S‐I performed statistically better for heart Dmean and V30Gy[RBE], lung Dmean and V5Gy[RBE], and liver Dmean, with slightly increased but clinically acceptable spinal cord Dmax. NTCP for liver was significantly better in Group S‐I. Conclusions IMPT plans in Group S‐I have better sparing of liver, heart, and lungs at the slight cost of spinal cord maximum dose protection, and are more interplay‐effect resilient compared to IMPT plans in Group R‐L. Our study supports the routine use of the S‐I oblique posterior beams for the treatments of distal esophageal carcinoma.

Background Rescanning is a common technique used in proton pencil beam scanning to mitigate the interplay effect. Advances in machine operating parameters across different generations of particle therapy systems have led to improvements in beam delivery time (BDT). However, the potential impact of these improvements on the effectiveness of rescanning remains an underexplored area in the existing research. Methods We systematically investigated the impact of proton machine operating parameters on the effectiveness of layer rescanning in mitigating interplay effect during lung SBRT treatment, using the CIRS phantom. Focused on the Hitachi synchrotron particle therapy system, we explored machine operating parameters from our institution's current (2015) and upcoming systems (2025A and 2025B). Accumulated dynamic 4D dose were reconstructed to assess the interplay effect and layer rescanning effectiveness. Results Achieving target coverage and dose homogeneity within 2% deviation required 6, 6, and 20 times layer rescanning for the 2015, 2025A, and 2025B machine parameters, respectively. Beyond this point, further increasing the number of layer rescanning did not further improve the dose distribution. BDTs without rescanning were 50.4, 24.4, and 11.4 s for 2015, 2025A, and 2025B, respectively. However, after incorporating proper number of layer rescanning (six for 2015 and 2025A, 20 for 2025B), BDTs increased to 67.0, 39.6, and 42.3 s for 2015, 2025A, and 2025B machine parameters. Our data also demonstrated the potential problem of false negative and false positive if the randomness of the respiratory phase at which the beam is initiated is not considered in the evaluation of interplay effect. Conclusion The effectiveness of layer rescanning for mitigating interplay effect is affected by machine operating parameters. Therefore, past clinical experiences may not be applicable to modern machines.

Introduction:Stereotactic ablative radiotherapy (SABR) is susceptible to challenges for tumours affected by intrafraction organ motion. This study aims to investigate the effect of breathing characteristics and plan complexity on the interplay effect.Methods:A patient-specific interplay effect evaluation was performed using in-house software with an alpha version of the treatment planning verification software Verisoft (PTW-Freiburg, Germany) on VMAT plans. The OCTAVIUS 4D phantom was used to acquire the static dose distribution, and the simulation approach was utilised to generate the moving dose distribution. The influence of plan complexity, PTV size, number of breaths, and motion amplitudes on the interplay effect were examined. The dose distribution of two extreme phases—end-inhale and end-exhale—was considered using the gamma criteria of 2%/2 mm for the interplay effect evaluation.Results:A strong correlation was found between the motion amplitude (p < 0.001) and the NBs (p < 0.001) with the gamma-passing rate. No correlation was found between the gamma-passing rate and the PTV size or plan complexity.Conclusion:The simulation tool allowed the analysis of a large number of breathing traces, demonstrating how free-breathing patients, suspected of high interplay, could be selected for other motion management solutions. The simulated cases showed strong interplay effects for long breathing periods with extended motion amplitudes in a small group of patients.

Background and purpose Proton stereotactic body radiotherapy (SBRT) offers superior dose conformity. However, its clinical application remains limited due to uncertainties from setup errors and respiratory motion. This study quantified the dosimetric robustness of proton SBRT for early‐stage non‐small cell lung cancer under combined setup and interplay uncertainties and investigated the association between dosimetric robustness and case‐specific characteristics. Methods Robust proton SBRT plans were generated considering setup and range uncertainties. Dosimetric robustness was evaluated by comparing the clinical target volume (CTV) coverage indices (V95%, V98%, and V100%) between the nominal condition and conditions incorporating combined setup and interplay uncertainties. The influence of respiratory amplitude, tumor volume, and mean tumor CT value on dosimetric robustness was assessed. Results CTV coverage remained stable under nominal conditions. However, dose degradation occurred under combined setup and interplay uncertainties, with the median CTV V100% decreased below 70%. Larger respiratory amplitudes and lower mean tumor CT values were associated with reduced dosimetric robustness. Conclusions Combined uncertainties significantly affected the dosimetric robustness of proton SBRT depending on case‐specific characteristics. Our exploratory analysis indicates the potential need for individualized robustness strategies in proton SBRT planning.

The Pencil Beam Scanning (PBS) technique in modern particle therapy offers a highly conformal dose distribution but poses challenges due to the interplay effect, an interaction between respiration-induced organ movement and PBS. This study evaluates the effectiveness of different volumetric rescanning strategies in mitigating this effect in liver cancer proton therapy. We used a Geant4-based Monte Carlo simulation toolkit, ‘TOPAS,’ and an image registration toolbox, ‘Elastix,’ to calculate 4D dose distributions from 5 patients’ four-dimensional computed tomography (4DCT). We analyzed the homogeneity index (HI) value of the Clinical Tumor Volume (CTV) at different rescan numbers and treatment times. Our results indicate that dose homogeneity stabilizes at a low point after a week of treatment, implying that both rescanning and fractionation treatments help mitigate the interplay effect. Notably, an increase in the number of rescans doesn’t significantly reduce the mean dose to normal tissue but effectively prevents high localized doses to tissue adjacent to the CTV. Rescanning techniques, based on statistical averaging, require no extra equipment or patient cooperation, making them widely accessible. However, the number of rescans, tumor location, diaphragm movement, and treatment fractionation significantly influence their effectiveness. Therefore, deciding the number of rescans should involve considering the number of beams, treatment fraction size, and total delivery time to avoid unnecessary treatment extension without significant clinical benefits. The results showed that 2–3 rescans are more clinically suitable for liver cancer patients undergoing proton therapy.

The interplay effect is a challenge when using proton scanning beams for the treatment of thoracic and abdominal cancers. The aim of this study was to evaluate the facility-specific interplay effect in terms of dose distortion and irradiation time for different beam delivery modalities, including free breathing (FB) irradiation, rescanning, deep inspiration breath-hold (DIBH), and respiratory gating. This study was carried out at a synchrotron-based facility with spot-scanning beam delivery. A motion phantom with a radiochromic film was used to measure dose distributions. Regular and irregular motion patterns were studied. Dose homogeneity and the gamma index were calculated to quantify the interplay effect. The interplay effect significantly decreased the homogeneity and gamma passing rate by 12% and 46%, respectively, when FB irradiation without motion mitigation was used for 20 mm peak-to-peak motion. Rescanning and DIBH partially mitigated the distortions but doubled the irradiation time, while gating provided the superior dose distribution with only a 25% increase in time compared to FB irradiation without mitigation. The interplay effect was a function of motion amplitude and varied with the beam delivery modality. Gating may be a more preferable technique for the synchrotron-based facility in terms of minimizing dose distortion and treatment time.