Evaluation of plastic materials for range shifting, range compensation, and solid-phantom dosimetry in carbon-ion radiotherapy

Purpose: Beam range control is the essence of radiotherapy with heavy charged particles. In con- ventional broad-beam delivery, fine range adjustment is achieved by insertion of range shifting and compensating materials. In dosimetry, solid phantoms are often used for convenience. These ma- terials should ideally be equivalent to water. In this study, the authors evaluated dosimetric water equivalence of four common plastics, high-density polyethylene (HDPE), polymethyl methacrylate (PMMA), polyethylene terephthalate (PET), and polyoxymethylene (POM).Methods: Using the Bethe formula for energy loss, the Gottschalk formula for multiple scattering, and the Sihver formula for nuclear interactions, the authors calculated the effective densities of the plastics for these interactions. The authors experimentally measured variation of the Bragg peak of carbon-ion beams by insertion of HDPE, PMMA, and POM, which were compared with analytical model calculations.Results: The theoretical calculation resulted in slightly reduced multiple scattering and severely in- creased nuclear interactions for HDPE, compared to water and the other plastics. The increase in attenuation of carbon ions for 20-cm range shift was experimentally measured to be 8.9% for HDPE, 2.5% for PMMA, and 0.0% for POM while PET was theoretically estimated to be in between PMMA and POM. The agreement between the measurements and the calculations was about 1% or better.Conclusions: For carbon-ion beams, POM was dosimetrically indistinguishable from water and the best of the plastics examined in this study. The poorest was HDPE, which would reduce the Bragg peak by 0.45% per cm range shift, although with marginal superiority for reduced multiple scattering. Between the two clear plastics, PET would be superior to PMMA in dosimetric water equivalence

Substance Made Manifest: Metaphysical and Semantic Implications of the Doctrine of Transubstantiation

Argues that traditional Catholic understanding of transubstantiation is obscured by modern metaphysics' neglect of the category of substance, and by modern semantic assumptions about how words signify

Relationship between electron density and effective densities of body tissues for stopping, scattering, and nuclear interactions of proton and ion beams

Purpose: In treatment planning of charged-particle radiotherapy, patient heterogeneity is conventionally modeled as variable-density water converted from CT images to best reproduce the stopping power, which may lead to inaccuracies in the handling of multiple scattering and nuclear interactions. Although similar conversions can be defined for these individual interactions, they would be valid only for specific CT systems and would require additional tasks for clinical application. This study aims to improve the practicality of the interaction-specific heterogeneity correction.Methods: The authors calculated the electron densities and effective densities for stopping power, multiple scattering, and nuclear interactions of protons and ions, using the standard elemental-composition data for body tissues to construct the invariant conversion functions. The authors also simulated a proton beam in a lung-like geometry and a carbon-ion beam in a prostate-like geometry to demonstrate the procedure and the effects of the interaction-specific heterogeneity correction.Results: Strong correlations were observed between the electron density and the respective effective densities, with which the authors formulated polyline conversion functions. Their effects amounted to 10% differences in multiple-scattering angle and nuclear interaction mean free path for bones compared to those in the conventional heterogeneity correction. Although their realistic effect on patient dose distributions would be generally small, it could be at the level of a few percent when a carbon-ion beam traverses a large bone.Conclusions: The present conversion functions are invariant and may be incorporated in treatment planning systems with a common function relating CT number to electron density. This will enable improved beam dose calculation while minimizing initial setup and quality management of the user\u27s specific system

Influence of nuclear interactions in polyethylene range compensators for carbon-ion radiotherapy

Purpose: A recent study revealed that polyethylene (PE) would cause extra carbon-ion attenua- tion per range shift by 0.45%/cm due to compositional differences in nuclear interactions. The present study aims to assess the influence of PE range compensators on tumor dose in carbon-ion radiotherapy.Methods: Carbon-ion radiation was modeled to be composed of primary carbon ions and secondary particles, for each of which the dose and the relative biological effectiveness (RBE) were estimated at a tumor depth in the middle of spread-out Bragg peak. Assuming exponential behavior for attenuation and yield of these components with depth, the PE effect on dose was calculated for clinical carbon- ion beams and was partly tested by experiment. The two-component model was integrated into a treatment-planning system and the PE effect was estimated in two clinical cases.Results: The attenuation per range shift by PE was 0.1%–0.3%/cm in dose and 0.2%–0.4%/cm in RBE-weighted dose, depending on energy and range-modulation width. This translates into reduction of RBE-weighted dose by up to 3% in extreme cases. In the treatment-planning study, however, the effect on RBE-weighted dose to tumor was typically within 1% reduction.Conclusions: The extra attenuation of primary carbon ions in PE was partly compensated by in- creased secondary particles for tumor dose. In practical situations, the PE range compensators would normally cause only marginal errors as compared to intrinsic uncertainties in treatment planning,patient setup, beam delivery, and clinical response

Giant High-Flow Type Pulmonary Arteriovenous Malformation: Coil Embolization with Flow Control by Balloon Occlusion and an Anchored Detachable Coil

Pulmonary arteriovenous malformations (PAVMs) are often treated by pushable fibered or non-fibered microcoils, using an anchor or scaffold technique or with an Amplatzer plug through a guiding sheath. When performing percutaneous transcatheter microcoil embolization, there is a risk of coil migration, particularly with high-flow type PAVMs. The authors report on a unique treatment in a patient with a giant high-flow PAVM whose nidus had a maximum diameter of 6 cm. A detachable coil, not detached from a delivery wire (an anchored detachable coil), was first placed in the feeding artery under flow control by balloon occlusion, and then multiple microcoils were packed proximally to the anchored detachable coil. After confirming the stability of the microcoils during a gradual deflation of the balloon, we finally released the first detachable coil. The nidus was reduced in size to 15 mm at one year postoperatively

Analysis of DOC and Ram for NSCLC

Background: Current clinical trials demonstrated that combination regimens comprising chemotherapy and immunotherapy lead to better patient outcomes compared to chemotherapy alone as the first line of treatment for non-small cell lung cancer (NSCLC). In addition, the combination therapy of docetaxel (Doc) and ramucirumab (Ram) was considered one of the standard treatments for advanced or relapsed NSCLC patients. However, little is known about the therapeutic responders of this combination therapy among previously treated NSCLC patients. In the present study, we aimed to identify predictive factors for therapeutic response, including programmed death-ligand 1 (PD-L1) expression in tumors, for Doc treatment in combination with Ram. Methods: We retrospectively analyzed a total of 135 advanced or relapsed NSCLC patients who were refractory to platinum-based chemotherapy at eleven institutions in Japan between July 2016 and November 2018. Results: Our observations showed that PD-L1 expression in tumors is not associated with the efficacy of combined therapy of Doc and Ram in previously treated NSCLC patients. Analysis of the patient clinical profiles indicated that prior treatment with immune checkpoint inhibitors (ICIs) is a reliable predictor for the good progression-free survival (PFS) to this combination therapy (P=0.041). Conclusions: Our retrospective study indicated that combination regimens comprising chemotherapy and ICIs followed by Doc and Ram could be an optimal therapeutic option for NSCLC patients regardless of the PD-L1 status of tumors. Further investigations are required to strengthen clinical evidence demonstrating the effectiveness of the combination therapy of Doc plus Ram in previously treated NSCLC patients

Structures and mechanisms of actin ATP hydrolysis

The major cytoskeleton protein actin undergoes cyclic transitions between the monomeric G-form and the filamentous F-form, which drive organelle transport and cell motility. This mechanical work is driven by the ATPase activity at the catalytic site in the F-form. For deeper understanding of the actin cellular functions, the reaction mechanism must be elucidated. Here, we show that a single actin molecule is trapped in the F-form by fragmin domain-1 binding and present their crystal structures in the ATP analog-, ADP-Pi-, and ADP-bound forms, at 1.15-Å resolutions. The G-to-F conformational transition shifts the side chains of Gln137 and His161, which relocate four water molecules including W1 (attacking water) and W2 (helping water) to facilitate the hydrolysis. By applying quantum mechanics/molecular mechanics calculations to the structures, we have revealed a consistent and comprehensive reaction path of ATP hydrolysis by the F-form actin. The reaction path consists of four steps: 1) W1 and W2 rotations; 2) PG–O3B bond cleavage; 3) four concomitant events: W1–PO3− formation, OH− and proton cleavage, nucleophilic attack by the OH− against PG, and the abstracted proton transfer; and 4) proton relocation that stabilizes the ADP-Pi–bound F-form actin. The mechanism explains the slow rate of ATP hydrolysis by actin and the irreversibility of the hydrolysis reaction. While the catalytic strategy of actin ATP hydrolysis is essentially the same as those of motor proteins like myosin, the process after the hydrolysis is distinct and discussed in terms of Pi release, F-form destabilization, and global conformational changes

Diagnostic Performance of 11C-choline PET/CT and FDG PET/CT in Prostate Cancer

We compared 11C-choline and FDG PET/CT scan findings for the staging and restaging of prostate cancer. Twenty Japanese prostate cancer patients underwent 11C-choline and FDG PET/CT before (n=5) or after (n=15) treatment. Using a five-point scale, we compared these scanning modalities regarding patient- and lesion-based diagnostic performance for local recurrence, untreated primary tumor, and lymph node and bony metastases. Of the 20 patients, documented local lesions, and node and bony metastases were present in 11 (55.0%), 9 (45.0%), and 13 (65.0%), respectively. The patient-based sensitivity/specificity/accuracy/area under the receiver-operating-characteristic curve (AUC) values for 11C-choline-PET/CT for diagnosing local lesions were 90.9% /100%/ 95.0% / 1.0, whereas those for FDG-PET/CT were 45.5% /100%/ 75.0% / 0.773. Those for 11C-choline-PET/CT for node metastasis were 88.9% /100%/ 95.0% / 0.944, and those for FDG-PET/CT were 44.4%/100%/75.0%/0.722. Those for 11C-choline-PET/CT for bone metastasis were 84.6%/100%/90.0%/0.951, and those for FDG-PET/CT were 76.9% /100%/ 85.0% / 0.962. The AUCs for local lesion and node metastasis differed significantly (p=0.0039, p=0.011, respectively). The lesion-based detection rates of 11C-choline compared to FDG PET/CT for local lesion, and node and bone metastases were 91.7% vs. 41.7%, 92.0% vs. 32.0%, and 94.8% vs. 83.0% (p=0.041, p=0.0030, p<0.0001), respectively. 11C-choline-PET/CT is more useful for the staging and restaging of prostate cancer than FDG-PET/CT in Japanese men