Efficacy and safety of FDG-PET for determining target volume during intensity-modulated radiotherapy for head and neck cancer involving the oral level.

PURPOSE: To determine the efficacy and safety of target volume determination by 18F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) for intensity-modulated radiation therapy (IMRT) for locally advanced head and neck squamous cell carcinoma (HNSCC) extending into the oral cavity or oropharynx. METHODS: We prospectively treated 10 consecutive consenting patients with HNSCC using IMRT, with target volumes determined by PET-CT. Gross tumor volume (GTV) and clinical target volume (CTV) at the oral level were determined by two radiation oncologists for CT, magnetic resonance imaging (MRI), and PET-CT. Differences in target volume (GTVPET, GTVCT, GTVMRI, CTVPET, CTVCT, and CTVMRI) for each modality and the interobserver variability of the target volume were evaluated using the Dice similarity coefficient and Hausdorff distance. Clinical outcomes, including acute adverse events (AEs) and local control were evaluated. RESULTS: The mean GTV was smallest for GTVPET, followed by GTVCT and GTVMRI. There was a significant difference between GTVPET and GTVMRI, but not between the other two groups. The interobserver variability of target volume with PET-CT was significantly less than that with CT or MRI for GTV and tended to be less for CTV, but there was no significant difference in CTV between the modalities. Grade ≤ 3 acute dermatitis, mucositis, and dysphagia occurred in 55%, 88%, and 22% of patients, respectively, but no grade 4 AEs were observed. There was no local recurrence at the oral level after a median follow-up period of 37 months (range, 15-55 months). CONCLUSIONS: The results suggest that the target volume determined by PET-CT could safely reduce GTV size and interobserver variability in patients with locally advanced HNSCC extending into the oral cavity or oropharynx undergoing IMRT. Trial registration UMIN, UMIN000033007. Registered 16 jun 2018, https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000037631.

Dosimetric comparison of four-dimensional computed tomography based internal target volume against variations in respiratory motion during treatment between volumetric modulated arc therapy and three-dimensional conformal radiotherapy in lung stereotactic body radiotherapy.

This study focused on the dosimetric impact of variations in respiratory motion during lung stereotactic body radiotherapy (SBRT). Dosimetric comparisons between volumetric modulated arc therapy (VMAT) and three-dimensional conformal radiotherapy (3DCRT) were performed using four-dimensional computed tomography (4DCT)-based internal target volumes (ITV). We created retrospective plans for ten patients with lung cancer who underwent SBRT using 3DCRT and VMAT techniques. A Delta4 Phantom + (ScandiDos, Uppsala, Sweden) was used to evaluate the dosimetric robustness of 4DCT-based ITV against variations in respiratory motion during treatment. We analyzed respiratory motion during treatment. Dose-volume histogram parameters were evaluated for the 95% dose (D95%) to the planning target volume (PTV) contoured on CT images obtained under free breathing. The correlations between patient respiratory parameters and dosimetric errors were also evaluated. In the phantom study, the average PTV D95% dose differences for all fractions were - 2.9 ± 4.4% (- 16.0 - 1.2%) and - 2.0 ± 2.8% (- 11.2 - 0.7%) for 3DCRT and VMAT, respectively. The average dose difference was < 3% for both 3DCRT and VMAT; however, in 5 out of 42 fractions in 3DCRT, the difference in PTV D95% was > 10%. Dosimetric errors were correlated with respiratory amplitude and velocity, and differences in respiratory amplitude between 4DCT and treatment days were the main factors causing dosimetric errors. The overall average dose error of the PTV D95% was small; however, both 3DCRT and VMAT cases exceeding 10% error were observed. Larger errors occurred with amplitude variation or baseline drift, indicating limited robustness of 4DCT-based ITV.

Effective clinical applications of Monte Carlo-based independent secondary dose verification software for helical tomotherapy.

PURPOSE: To investigate the scope of the effective clinical application of Monte Carlo (MC)-based independent dose verification software for helical tomotherapy. METHODS: DoseCHECK was selected as the MC-based dose calculation software. First, the dose calculation accuracy of DoseCHECK was evaluated with film and chamber measurements in a water-equivalent phantom. Second, the dose calculation accuracy was examined in several heterogeneous materials. Finally, dosimetric comparisons between DoseCHECK and the treatment planning system (TPS) were performed for clinical patient plans. Prostate IMRT, head and neck IMRT (HN), total body irradiation (TBI), and brain stereotactic radiotherapy (SRT) were evaluated. RESULT: The DoseCHECK calculations agreed with the chamber and film measurements in the homogenous phantom. For heterogeneous phantom cases, the dose differences between DoseCHECK and TPS were within 3 %, except in air, in which large dose differences of 20 % were observed. In clinical patient plans, the median dose differences between the lung Dmean in TBI cases and the normal brain Dmean in brain SRT cases were significantly >3 %. For HN and brain SRT cases, the median target dose differences were >3 %. CONCLUSION: Our results show that independent dose verification with the MC algorithm can detect systematic errors caused by the lack of heterogeneity correction in the TPS. In particular, MC-based independent dose verification is required for HN, TBI, and brain SRT cases in helical tomotherapy.

Intracranial stereotactic radiotherapy in off-isocenter target with SyncTraX FX4.

PURPOSE: We investigated the localization accuracy of the off-isocenter targets using SyncTraX FX4, a new image registration device. METHODS: In a phantom study, we used a MultiMet-WL Cube with metal targets at different distances from the isocenter. Image registrations were performed with SyncTraX and cone-beam computed tomography (CBCT). Nineteen fields with different gantry, collimator, and couch angles were delivered to each target. Localization errors of the off-isocenter targets were then evaluated. In a clinical study, localization accuracy was evaluated for 32 patients. First, image registration was performed using SyncTraX, and the accuracy of patient positioning was evaluated using CBCT. Next, positioning corrections were performed for intracranial setup errors exceeding the threshold (0.5 mm/0.5°) in each field. Finally, total setup uncertainty was evaluated using CBCT. Differences in dosimetric errors from planned doses between no patient positioning corrections during treatment and positioning corrections with SyncTraX were also evaluated. RESULTS: In the phantom study, the positioning accuracy on targets up to 7 cm from the isocenter was within 1 mm. In the clinical practice, the localization accuracies of SyncTraX were 0.35 ± 0.39 mm, 0.30 ± 0.24 mm, and 0.03 ± 0.27 mm in the lateral, vertical, and longitudinal directions, respectively. Post-treatment setup errors were reduced by correcting intrafractional setup errors with SyncTraX during treatment. Positioning corrections with SyncTraX reduced the maximum dosimetric error from 1.6% to 1.0%. CONCLUSIONS: SyncTraX provides satisfactory localization accuracy for the off-isocenter targets within 7 cm. SyncTraX reduce dosimetric errors caused by intrafractional setup errors during treatment.

The effects of rotational setup errors in total body irradiation using helical tomotherapy.

PURPOSE: Helical tomotherapy (HT) is a form of intensity-modulated radiation therapy that is employed in total body irradiation (TBI). Because TBI targets the whole body, accurate setup positioning at the edge of the treatment volume is made difficult by the whole-body rotational posture. The purpose of this study is to clarify the tolerance for rotational setup error (SE) in the vertical direction. In addition, we perform a retrospective analysis of actually irradiated dose distributions using previous patients' irradiation data. METHODS: To clarify the effects of rotational SE on the dose distribution, the planned CT images of 10 patients were rotated by 1-5° in the vertical (pitch) direction to create a pseudo-rotational SE image. Then, the effect of the magnitude of the rotational SE on the dose distribution was simulated. In addition, the irradiated dose to the patients was analyzed by obtaining recalculated dose distributions using megavoltage CT images acquired before treatment. RESULTS: The simulation results showed that the average value of the lung volume receiving at least 10 Gy did not exceed the allowable value when the SE value was ≤2°. When the rotational SE was ≤3°, it was possible to maintain the clinical target volume dose heterogeneity within ±10% of the prescribed dose, which is acceptable according to the guidelines. A retrospective analysis of previous patients' irradiation data showed their daily irradiation dose distribution. The dose to the clinical target volume was reduced by up to 3.4% as a result of the residual rotational SE. Although whole-course retrospective analyses showed a statistically significant increase in high-dose areas, the increase was only approximately 1.0%. CONCLUSIONS: Dose errors induced by rotational SEs of ≤2° were acceptable in this study.

A prospective feasibility study of a 1-mm bolus for postmastectomy radiotherapy.

BACKGROUND: The optimal chest wall bolus regimen for postmastectomy radiotherapy (PMRT) remains unknown. We aimed to prospectively evaluate the use of a 1-mm-thick daily tissue-equivalent bolus in patients who received PMRT using thermoluminescent dosimeters (TLDs) and skin toxicity assessment. METHODS: Patients with a 1-mm-thick daily bolus during PMRT were prospectively enrolled at The Juntendo University Hospital. The surface dose was measured in vivo under the 1-mm-thick bolus on the chest wall. We assessed the acute skin toxicity weekly during PMRT, and 1, 2, 4, and 12 weeks after the completion of PMRT. RESULTS: A total of 19 patients aged 32-79 years old received PMRT from July 2019 to January 2020. All patients completed the protocol treatment without interruptions, and the median follow-up was 32 weeks. In vivo dosimetry analysis revealed surface doses between 77 and 113% of the prescribed dose, with a mean of 92% of the prescribed radiation dose, and a standard deviation of 7% being delivered. Grade 2 dermatitis was found in 10 patients (53%), and Grade 3 dermatitis was found in one patient (5%). All cases of Grade 2 and 3 dermatitis were improved 4 weeks after PMRT. There were no cases of Grade 4 dermatitis and no chest wall recurrences during the treatment or follow-up period. CONCLUSIONS: Results confirmed the feasibility of using a 1-mm-thick daily bolus for PMRT, exhibiting an appropriate dose buildup and acceptable skin toxicity without treatment interruptions. TRIAL REGISTRATION: The University Hospital Medical Information Network Clinical Trials Registry, UMIN000035773 . Registered 1 July 2019.

Dosimetric assessment of bolus for postmastectomy radiotherapy.

There remains wide variation in the use of chest wall boluses for postmastectomy radiotherapy, which may result from the need for 2 treatment plans with the commonly used half-time tissue-equivalent 5-mm-thick bolus to achieve a full surface dose. To establish a bolus method requiring one treatment plan, we assessed the surface dose of a thinner daily bolus for all treatment fractions and compared it against the half-time 5-mm-thick bolus. In this basic study, we specifically investigated dosage achieved when using the following: (1) the existing bolus protocol, a half-time 5-mm-thick tissue-equivalent Clearfit bolus (Fujidenolo Inc., Aichi, JP); (2) no bolus; and (3) daily 1-, 2-, and 3-mm-thick Clearfit boluses at 4 and 6 MV photons. Dosimetric measurements were then taken in an anthropomorphic phantom to study the effect of each regimen on the surface doses, and the mean surface doses of the daily thinner boluses were compared with the existing bolus protocol by the Welch 2-sample t test. The mean surface doses for the existing bolus protocol, no bolus, and daily 1-, 2-, and 3-mm-thick boluses were 68% (range, 59% to 77%), 53% (41% to 66%), 73% (60% to 83%), 77% (66% to 87%), and 82% (75% to 91%) of the prescription dose at 4 MV, respectively; the corresponding values at 6 MV were 71% (63% to 79%), 50% (39% to 60%), 72% (56% to 83%), 81% (68% to 90%), and 89% (80 to 97%) of the prescription dose. The mean surface doses were comparable between the existing bolus protocol and the 1-mm-thick daily bolus at 4 and 6 MV. In conclusion, the mean surface dose of a 1-mm-thick bolus approximate that of a half-time 5-mm-thick bolus at 4 and 6 MV. As such, we have started a prospective clinical study on the safety and efficacy of a 1-mm-thick bolus for postmastectomy radiotherapy.

Development of a rotational set-up correction device for stereotactic head radiation therapy: A performance evaluation.

We developed a new head supporting device to provide accurate correction of rotational setup during image-guided radiation therapy (IGRT), evaluating its correction performance and the efficacy of dose distribution in stereotactic radiotherapy (SRT) using a helical tomotherapy (HT) system. The accuracy of rotational motion was measured using an electronic inclinometer; we compared device angles and measurement values from 0.0° to 3.0°. The correction accuracy was investigated based on the distance between rotational centers in the device and on megavoltage computed tomography (MVCT); the correction values were compared using distances in the range of 0.0-9.0 cm using a head phantom with a rotational error of 1.5°. For an SRT with a simultaneous integrated boost plan and a rotational error of 3.0° in yaw angle using a head phantom, and for a single-isocenter SRT for multiple brain metastases in the data of three patients, dosimetric efficacy of the HT unit was evaluated for calculated dose distributions with MVCT after rotational correction. This device can correct pitch and yaw angles within 0.3° and can be corrected to within 0.5° for each rotational angle according to the result of MVCT correction regardless of the rotational center position. In the head phantom study, the device had a beneficial impact on rotational correction; D99% for the target improved by approximately 10% with rotational correction. Using patient data with the device, the mean difference based on the treatment planning data was 0.3% for D99% and -0.1% for coverage index to the target. Our rotational setup correction device has high efficacy, and can be used for IGRT.

Appropriate treatment planning method for field joint dose in total body irradiation using helical tomotherapy.

Total body irradiation (TBI) using helical tomotherapy (HT) has advantages over the standard linear accelerator-based approach to the conditioning regimen for hematopoietic cell transplantation. However, the radiation field has to be divided into two independent irradiation plans to deliver a homogeneous dose to the whole body. A clinical target volume near the skin increases the skin surface dose; therefore, high- or low-dose regions arise depending on the set-up position accuracy because the two radiation fields are somewhat overlapped or separated. We aimed to determine an adequate treatment planning method robust to the set-up accuracy for the field joint dose distribution using HT-TBI. We calculated treatment plans reducing target volumes at the interface between the upper and lower body irradiations and evaluated these joint dose distributions via simulation and experimental studies. Target volumes used for the optimization calculation were reduced by 0, 0.5, 1.0, 2.0, 2.5, and 3.0 cm from the boundary surface on the upper and lower sides. Combined dose distributions with set-up error simulated by modifying coordinate positions were investigated to find the optimal planning method. In the ideal set-up position, the target volume without a gap area caused field junctional doses of up to approximately 200%; therefore, target volumes reduced by 2.0-3.0 cm could suppress the maximum dose to within 150%. However, with set-up error, high-dose areas exceeding 150% and low-dose areas below 100% were found with 2.0 and 3.0 cm target volume reduction. Using the dynamic jaw (DJ) system, dose deviations caused by set-up error reached approximately 20%, which is not suitable for HT-TBI. Moreover, these dose distributions can be easily adjusted when combined with the intensity modulation technique for field boundary regions. The results of a simulation and experimental study using a film dosimetry were almost identical, which indicated that reducing the target volume at the field boundary surface by 2.5 cm produces the most appropriate target definition.

[Impact of the Infrared Monitor Signal Pattern on Accuracy of Target Imaging in 4-dimensional Cone-beam Computed Tomography].

To realize the high precision radiotherapy, localized radiation field of the moving target is very important, and visualization of a temporal location of the target can help to improve the accuracy of the target localization. However, conditions of the breathing and the patient's own motion differ from the situation of the treatment planning. Therefore, positions of the tumor are affected by these changes. In this study, we implemented a method to reconstruct target motions obtained with the 4D CBCT using the sorted projection data according to the phase and displacement of the extracorporeal infrared monitor signal, and evaluated the proposed method with a moving phantom. In this method, motion cycles and positions of the marker were sorted to reconstruct the image, and evaluated the image quality affected by changes in the cycle, phase, and positions of the marker. As a result, we realized the visualization of the moving target using the sorted projection data according to the infrared monitor signal. This method was based on the projection binning, in which the signal of the infrared monitor was surrogate of the tumor motion. Thus, further major efforts are needed to ensure the accuracy of the infrared monitor signal.

In vitro metabolic engineering for the salvage synthesis of NAD(.).

Excellent thermal and operational stabilities of thermophilic enzymes can greatly increase the applicability of biocatalysis in various industrial fields. However, thermophilic enzymes are generally incompatible with thermo-labile substrates, products, and cofactors, since they show the maximal activities at high temperatures. Despite their pivotal roles in a wide range of enzymatic redox reactions, NAD(P)(+) and NAD(P)H exhibit relatively low stabilities at high temperatures, tending to be a major obstacle in the long-term operation of biocatalytic chemical manufacturing with thermophilic enzymes. In this study, we constructed an in vitro artificial metabolic pathway for the salvage synthesis of NAD(+) from its degradation products by the combination of eight thermophilic enzymes. The enzymes were heterologously produced in recombinant Escherichia coli and the heat-treated crude extracts of the recombinant cells were directly used as enzyme solutions. When incubated with experimentally optimized concentrations of the enzymes at 60°C, the NAD(+) concentration could be kept almost constant for 15h.