Assessing alimentary tract radiation in liver cancer treatment with proton beam therapy: a PET/CT imaging study.

BACKGROUND: Proton beams deposit energy along their path, abruptly stopping and generating various radioactive particles, including positrons, along their trajectory. In comparison with traditional proton beam therapy, scanning proton beam therapy is effective in delivering proton beams to irregularly shaped tumors, reducing excessive radiation exposure to the alimentary tract during the treatment of liver cancer. METHODS: In this study, we utilized positron emission tomography/computed tomography (PET/CT) imaging to assess the total amount of radiation to the alimentary tract during liver cancer treatment with proton beam therapy, involving the administration of complex irradiation in 13 patients. RESULTS: This approach resulted in the prevention of excess radiation. The planned radiation restraint doses for the colon exhibited a significant correlation with the PET values of the colon (correlation coefficient 0.8384, P = .0003). Likewise, the scheduled radiation restraint doses for the gastroduodenum were correlated with the PET values of the gastroduodenum (correlation coefficient 0.5397, P = .0569). CONCLUSIONS: PET/CT conducted after proton beam therapy is useful for evaluating excess radiation in the alimentary tract. Proton beam therapy in liver cancer, assessed via PET/CT, effectively reduced alimentary tract radiation, which is vital for optimizing treatments and preventing excess exposure.

Long-term stability of a PTW 34070 large-area parallel ionization chamber in clinical proton scanning beams.

PURPOSE: In the modeling of beam data for proton therapy planning systems, absolute dose measurements are performed utilizing a Bragg peak chamber (BPC), which is a parallel-plate ionization chamber. The long-term stability of the BPC is crucial for ensuring accurate absolute dose measurement. The study aims to assess the long-term stability of the BPC in clinical proton pencil beam scanning delivery. METHODS: The long-term stability evaluation focused on the BPC-Type 34070 (PTW Freiburg, Germany), utilizing clinical proton scanning beams from December 2022 to November 2023. Monthly investigations were conducted to evaluate the response and cross-calibration factor of the BPC and a reference chamber, employing the spread-out Bragg peak (SOBP) field. Additionally, assessments were made regarding the BPC's response to monoenergetic beams, along with an examination of the impact of polarity and ion recombination on the BPC. RESULTS: The response and cross-calibration factor of the BPC varied up to 1.9% and 1.8%, respectively, while the response of the reference chamber remained within a 0.5% range. The BPC's response to the mono-energetic beams varied up to 2.0% across all energies, demonstrating similar variation trends in both the SOBP field and mono-energetic beams. Furthermore, the variations in polarity and ion recombination effect remained stable within a 0.4% range throughout the year. Notably, the reproducibility of the BPC remained high for each measurement conducted, whether for the SOBP field or mono-energetic beams, with a maximum deviation observed at 0.1%. CONCLUSIONS: The response and cross-calibration factor of the BPC demonstrated significant variations, with maximum changes of 1.9% and 1.8%, respectively. However, the reproducibility of the BPC remained consistently high for each measurement. It is recommended that when conducting absolute dose measurements using a BPC, its response should be compared and corrected against the reference chamber for each measurement.

Effectiveness of robust optimization against geometric uncertainties in TomoHelical planning for prostate cancer.

BACKGROUND: Geometrical uncertainties in patients can severely affect the quality of radiotherapy. PURPOSE: We evaluated the dosimetric efficacy of robust optimization for helical intensity-modulated radiotherapy (IMRT) planning in the presence of patient setup uncertainty and anatomical changes. METHODS: Two helical IMRT plans for 10 patients with localized prostate cancer were created using either minimax robust optimization (robust plan) or a conventional planning target volume (PTV) margin approach (PTV plan). Plan robustness was evaluated by creating perturbed dose plans with setup uncertainty from isocenter shifts and anatomical changes due to organ variation. The magnitudes of the geometrical uncertainties were based on the patient setup uncertainty considered during robust optimization, which was identical to the PTV margin. The homogeneity index, and target coverage (TC, defined as the V100% of the clinical target volume), and organs at risk (OAR; rectum and bladder) doses were analyzed for all nominal and perturbed plans. A statistical t-test was performed to evaluate the differences between the robust and PTV plans. RESULTS: Comparison of the nominal plans showed that the robust plans had lower OAR doses and a worse homogeneity index and TC than the PTV plans. The evaluations of robustness that considered setup errors more than the PTV margin demonstrated that the worst-case perturbed scenarios for robust plans had significantly higher TC while maintaining lower OAR doses. However, when anatomical changes were considered, improvement in TC from robust optimization was not observed in the worst-case perturbed plans. CONCLUSIONS: For helical IMRT planning in localized prostate cancer, robust optimization provides benefits over PTV margin-based planning, including better OAR sparing, and increased robustness against systematic patient-setup errors.

A novel internal target volume definition based on velocity and time of respiratory target motion for external beam radiotherapy.

This study aimed to develop a novel internal target volume (ITV) definition for respiratory motion targets, considering target motion velocity and time. The proposed ITV was evaluated in respiratory-gated radiotherapy. An ITV modified with target motion velocity and time (ITVvt) was defined as an ITV that includes a target motion based on target motion velocity and time. The target motion velocity was calculated using four-dimensional computed tomography (4DCT) images. The ITVvts were created from phantom and clinical 4DCT images. The phantom 4DCT images were acquired using a solid phantom that moved with a sinusoidal waveform (peak-to-peak amplitudes of 10 and 20 mm and cycles of 2-6 s). The clinical 4DCT images were obtained from eight lung cancer cases. In respiratory-gated radiotherapy, the ITVvt was compared with conventional ITVs for beam times of 0.5-2 s within the gating window. The conventional ITV was created by adding a uniform margin as the maximum motion within the gating window. In the phantom images, the maximum volume difference between the ITVvt and conventional ITV was -81.9%. In the clinical images, the maximum volume difference was -53.6%. Shorter respiratory cycles and longer BTs resulted in smaller ITVvt compared with the conventional ITV. Therefore, the proposed ITVvt plan could be used to reduce treatment volumes and doses to normal tissues.

Comparing Efficacy Between Robust and PTV Margin-based Optimizations for Interfractional Anatomical Variations in Prostate Tomotherapy.

BACKGROUND/AIM: Interfractional anatomical variations cause considerable differences between planned and actual radiotherapy doses. This study aimed to investigate the efficacy of robust and planning target volume (PTV) margin-based optimizations for the anatomical variations in helical tomotherapy for prostate cancer. PATIENTS AND METHODS: Ten patients underwent treatment-planning kilovolt computed tomography (kVCT) and daily megavolt computed tomography (MVCT). Two types of nominal plans, with a prescription of 60 Gy/20 fractions, were created using robust and PTV margin-based optimizations on kVCT for each patient. Subsequently, the daily estimated doses were recalculated using nominal plans, and all available MVCTs modified the daily patient-setup errors. Due to the difference in dose calculation accuracy between kVCT and MVCT, three scenarios with dose corrections of 1, 2, and 3% were considered in the recalculation process. The dosimetric metrics, including target coverage with the prescription dose, Paddick's conformity index, homogeneity index, and mean dose to the rectum, were analyzed. RESULTS: A dosimetric comparison of the nominal plans demonstrated that the robust plans had better dose conformity, lower target coverage, and dose homogeneity than the PTV plans. In the daily estimated doses of any dose-corrected scenario, the target coverage and dose sparing to the rectum in the robust plans were significantly higher than those in the PTV plans, whereas dose conformity and homogeneity were identical to those of the nominal case. CONCLUSION: Robust optimization is recommended as it accounts for anatomical variations during treatment regarding target coverage in helical tomotherapy plans for prostate cancer.

Evaluating optimal quality assurance and quality control conditions of activation measurements at the accelerator-based boron neutron capture therapy system employing a lithium target.

Evaluating neutron output is important to ensure proper dose delivery for patients in boron neutron capture therapy (BNCT). It requires efficient quality assurance (QA) and quality control (QC) while maintaining measurement accuracy. This study investigated the optimal measurement conditions for QA/QC of activation measurements using a high-purity germanium (HP-Ge) detector in an accelerator-based boron neutron capture therapy (AB-BNCT) system employing a lithium target. The QA/QC uncertainty of the activation measurement was evaluated based on counts, reproducibility, and standard radiation source uncertainties. Measurements in a polymethyl methacrylate (PMMA) cylindrical phantom using aluminum-manganese (Al-Mn) foils and aluminum-gold (Al-Au) foils and measurements in a water phantom using gold wire with and without cadmium cover were performed to determine the optimal measurement conditions. The QA/QC uncertainties of the activation measurements were 4.5% for Au and 4.6% for Mn. The optimum irradiation proton charge and measurement time were determined to be 36 C and 900 s for measurements in a PMMA cylindrical phantom, 7.0 C and 900 s for gold wire measurements in a water phantom, and 54 C and 900 s at 0-2.2 cm depth and 3,600 s at deeper depths for gold wire measurements with cadmium cover. Our results serve as a reference for determining measurement conditions when performing QA/QC of activation measurements using HP-Ge detectors at an AB-BNCT employing a lithium target.

Impact of interplay effects on spot scanning proton therapy with motion mitigation techniques for lung cancer: SFUD versus robustly optimized IMPT plans utilizing a four-dimensional dynamic dose simulation tool.

BACKGROUND: The interaction between breathing motion and scanning beams causes interplay effects in spot-scanning proton therapy for lung cancer, resulting in compromised treatment quality. This study investigated the effects and clinical robustness of two types of spot-scanning proton therapy with motion-mitigation techniques for locally advanced non-small cell lung cancer (NSCLC) using a new simulation tool (4DCT-based dose reconstruction). METHODS: Three-field single-field uniform dose (SFUD) and robustly optimized intensity-modulated proton therapy (IMPT) plans combined with gating and re-scanning techniques were created using a VQA treatment planning system for 15 patients with locally advanced NSCLC (70 GyRBE/35 fractions). In addition, gating windows of three or five phases around the end-of-expiration phase and two internal gross tumor volumes (iGTVs) were created, and a re-scanning number of four was used. First, the static dose (SD) was calculated using the end-of-expiration computed tomography (CT) images. The four-dimensional dynamic dose (4DDD) was then calculated using the SD plans, 4D-CT images, and the deformable image registration technique on end-of-expiration CT. The target coverage (V98%, V100%), homogeneity index (HI), and conformation number (CN) for the iGTVs and organ-at-risk (OAR) doses were calculated for the SD and 4DDD groups and statistically compared between the SD, 4DDD, SFUD, and IMPT treatment plans using paired t-test. RESULTS: In the 3- and 5-phase SFUD, statistically significant differences between the SD and 4DDD groups were observed for V100%, HI, and CN. In addition, statistically significant differences were observed for V98%, V100%, and HI in phases 3 and 5 of IMPT. The mean V98% and V100% in both 3-phase plans were within clinical limits (> 95%) when interplay effects were considered; however, V100% decreased to 89.3% and 94.0% for the 5-phase SFUD and IMPT, respectively. Regarding the significant differences in the deterioration rates of the dose volume histogram (DVH) indices, the 3-phase SFUD plans had lower V98% and CN values and higher V100% values than the IMPT plans. In the 5-phase plans, SFUD had higher deterioration rates for V100% and HI than IMPT. CONCLUSIONS: Interplay effects minimally impacted target coverage and OAR doses in SFUD and robustly optimized IMPT with 3-phase gating and re-scanning for locally advanced NSCLC. However, target coverage significantly declined with an increased gating window. Robustly optimized IMPT showed superior resilience to interplay effects, ensuring better target coverage, prescription dose adherence, and homogeneity than SFUD. TRIAL REGISTRATION: None.

Relative Biological Effectiveness Values of Spot-scanning Proton Beam Therapy at Shonan Kamakura General Hospital.

BACKGROUND/AIM: This study aimed to confirm the relative biological effectiveness (RBE) values of the proton beam therapy (PBT) system installed in Shonan Kamakura General Hospital. MATERIALS AND METHODS: Clonogenic cell-survival assays were performed with a human salivary gland (HSG) cell line, a human tongue squamous-cell carcinoma cell line (SAS), and a human osteosarcoma cell line (MG-63). Cells were irradiated with proton beams and X-rays with different doses (1.8, 3.6, 5.5, and 7.3 Gy for proton beams, and 2, 4, 6, and 8 Gy for X-rays). Proton beam irradiation used spot-scanning methods and three different depths (at the proximal, center, and distal sides of the spread-out Bragg peak). RBE values were obtained from a comparison of the dose that resulted in a surviving fraction of 10% (D10). RESULTS: D10 of proton beams at the proximal, center, and distal sides and X-rays in HSG were 4.71, 4.71, 4.51, and 5.25 Gy, respectively; those in SAS were 5.08, 5.04, 5.01, and 5.59 Gy, respectively; and those in MG-63 were 5.36, 5.42, 5.12, and 6.06 Gy, respectively. The RBE10 values at the proximal, center, and distal sides in HSG were 1.11, 1.11, and 1.16 respectively; those in SAS were 1.10, 1.11, and 1.12, respectively; and those in MG-63 were 1.13, 1.12, and 1.18, respectively. CONCLUSION: RBE10 values of 1.10-1.18 were confirmed by in vitro experiments using the PBT system. These results are considered acceptable for clinical use in terms of therapeutic efficacy and safety.

Deficient maternal behavior in multiparous Pou3f2⊿ mice is associated with an impaired exploratory activity.

Mammalian adult females develop specialized body parts, namely mammary glands and uterus, and exhibit specialized maternal behavior, lactation/nursing and care for their offspring. As the brain plays an essential role in regulating related physiological functions in the body, the morphology or function of the mammalian brain has been modified to manage newly equipped structures and functions. However, this evolutionary process is largely unknown. Pou3f2/Brn2 is an evolutionarily remarkable gene as it contains mammal-specific base sequences encoding three stretches of homopolymeric amino acids (polyAAs): poly-glycine (polyG), poly-glutamine (polyQ), and poly-proline (polyP). Previously, we demonstrated that POU3F2 acquisition of mammal-specific polyAAs contributed to the establishment of behaviors characteristic of mammals. Here, we demonstrated that Pou3f2⊿ mice displayed basic features required for maternal care. However, Pou3f2⊿ mice exhibited deficits in the reproductive performance and maternal behavior, which were not fully improved by multiparas. Therefore, we extensively investigated pup retrieval behavior and discovered that the retrieval and the exploratory behaviors were impaired in Pou3f2⊿ female mice, but not in males. Altogether, our data suggest that POU3F2 acquisition of mammal-specific polyAAs contributes to the continuous awareness and curiosity needed for maternal interaction.