Boron neutron capture therapy for cutaneous angiosarcoma and malignant melanoma: First in-human phase I clinical trial.

BACKGROUND AND PURPOSE: Definitive radiotherapy for patients with scalp angiosarcoma has a poor prognosis, often resulting in severe skin adverse events. Additionally, malignant melanoma is known for its radioresistant nature. Boron neutron capture therapy (BNCT) may address these challenges due to the high uptake capacity of boron drugs in these cancer types. We aimed to determine the treatment dose for BNCT and evaluate the incidence of acute adverse events AEs following BNCT in patients with primary or recurrent angiosarcoma/malignant melanoma of the skin. MATERIALS AND METHODS: This was a single-center, non-randomized clinical trial with a three-step dose escalation plan, involving maximum skin doses of 12, 15, and 18 Gy-Eq following a 3 + 3 design. The patients underwent BNCT between November 2019 and April 2022. The primary endpoint was to evaluate the incidence of acute adverse events. RESULTS: Ten patients (scalp angiosarcomanine, forefinger malignant melanoma: one) were included. The median target lesion size was 46.5 (range: 20-145) mm. A transient asymptomatic increase in serum amylase level was the only grade 3 adverse event. The best overall response rate within 180 days was 70 % (median tumor shrinkage rate: 77.5 % [4.9-100 %]). CONCLUSIONS: BNCT with a dose of 18 Gy-Eq is a feasible treatment option, demonstrating a favorable safety profile and a high response rate in patients with primary or recurrent angiosarcoma or malignant melanoma of the skin.

A method for delivering the required neutron fluence in an accelerator-based boron neutron capture therapy system employing a lithium target.

Accelerator-based boron neutron capture therapy (BNCT) systems employing a solid-state lithium target indicated the reduction of neutron flux over the lifetime of a target, and its reduction could represent the neutron flux model. This study proposes a novel compensatory approach for delivering the required neutron fluence and validates its clinical applicability. The proposed approach relies on the neutron flux model and the cumulative sum of real-time measurements of proton charges. The accuracy of delivering the required neutron fluence for BNCT using the proposed approach was examined in five Li targets. With the proposed approach, the required neutron fluence could be delivered within 3.0%, and within 1.0% in most cases. However, those without using the proposed approach exceeded 3.0% in some cases. The proposed approach can consider the neutron flux reduction adequately and decrease the effect of uncertainty in neutron measurements. Therefore, the proposed approach can improve the accuracy of delivering the required fluence for BNCT even if a neutron flux reduction is expected during treatment and over the lifetime of the Li target. Additionally, by adequately revising the approach, it may apply to other type of BNCT systems employing a Li target, furthering research in this direction.

Feasibility of accelerated partial breast irradiation with strut-adjusted volume implant brachytherapy in Japan focusing on dosimetry and acute toxicity: a Japanese multi-institutional prospective study.

BACKGROUND: A Japanese multi-institutional prospective study was initiated to investigate the effectiveness and safety of accelerated partial breast irradiation (APBI) using strut-adjusted volume implant (SAVI) brachytherapy, with subjects registered between 2016 and 2021. Herein, we report the preliminary results on the feasibility of this treatment modality in Japan, focusing on the registration process, dosimetry, and acute toxicities. PATIENTS AND METHODS: Primary registration was conducted before breast-conserving surgery (BCS) and the eligibility criteria included the following: age ≥ 40 years, tumor unifocal and unicentric, ≤ 3 cm in diameter, cN0M0, proven ductal, mucinous, tubular, medullary, or lobular carcinoma by needle biopsy. Secondary registration was conducted after BCS had been performed leaving a cavity for device implantation and pathological evaluations, and the eligibility criteria were as follows: negative surgical margin, tumor ≤ 3 cm in diameter on gross pathological examination, histologically confirmed ductal, mucinous, tubular medullary, colloid, or lobular carcinoma, pN0, L0V0, no extensive ductal component, no initiation of chemotherapy within 2 weeks of the brachytherapy APBI planning with SAVI was performed for the patients successfully entered in the study by the secondary registration process, and the treatment was administered at the dose of 34 Gy in 10 fractions administered twice daily. RESULTS: Between 2016 and 2021, 64 women were enrolled in the study through primary registration, of which 19 were excluded from the secondary registration process, and in one, it was deemed impossible to comply with the dose constraints established during treatment planning. After the exclusion of these latter 20 patients, we treated the remaining 44 patients by APBI with SAVI. The dose constraints could be adhered to in all the patients, but re-planning was necessitated in 3 patients because of applicator movement during the treatment period. Grade 2 acute toxicities were observed in 18% of all patients, but more severe acute toxicities than Grade 2 were not observed in any of the patients. CONCLUSION: APBI with SAVI brachytherapy is feasible in Japan from the aspects of compliance with dose constraints and frequency of acute toxicities.

Acral cutaneous malignant melanoma treated with linear accelerator-based boron neutron capture therapy system: a case report of first patient.

This study reports the first patient treatment for cutaneous malignant melanoma using a linear accelerator-based boron neutron capture therapy (BNCT) system. A single-center open-label phase I clinical trial had been conducted using the system since November 2019. A patient with a localized node-negative acral malignant melanoma and the largest diameter of the tumor ≤ 15 cm who refused primary surgery and chemotherapy was enrolled. After administering boronophenylalanine (BPA), a single treatment of BNCT with the maximum dose of 18 Gy-Eq delivered to the skin was performed. The safety and efficacy of the accelerator-based BNCT system for treating localized cutaneous malignant melanoma were evaluated. The first patient with cutaneous malignant melanoma in situ on the second finger of the left hand did not develop dose-limiting toxicity in the clinical trial. After BNCT, the treatment efficacy was gradually observed, and the patient achieved PR within 6 months and CR within 12 months. Moreover, during the follow-up period of 12 months after BNCT, the patient did not exhibit a recurrence without any treatment-related grade 2 or higher adverse events. Although grade 1 adverse events of dermatitis, dry skin, skin hyperpigmentation, edema, nausea, and aching pain were noted in the patient, those adverse events were relieved without any treatment. This case report shows that the accelerator-based BNCT may become a promising treatment modality for cutaneous malignant melanoma. We expect further clinical trials to reveal the efficacy and safety of the accelerator-based BNCT for cutaneous malignant melanoma.

Correlation between L-amino acid transporter 1 expression and 4-borono-2-18 F-fluoro-phenylalanine accumulation in humans.

BACKGROUND: The correlation between L-type amino acid transporter 1 (LAT1) expression and 4-borono-2-18 F-fluoro-phenylalanine (18 F-FBPA) accumulation in humans remains unclear. This study aimed to investigate the correlation between LAT1 expression in tumor tissues and 18 F-FBPA accumulation in patients with head and neck cancer who participated in a clinical trial of 18 F-FBPA positron emission tomography (PET). METHODS: Altogether, 28 patients with head and neck cancer who participated in a clinical trial of 18 F-FBPA PET at our institution between March 2012 and January 2018 were included. Correlations between standardized uptake values (SUVs); the maximum SUV (SUVmax ), the mean SUV within a 1 cm3 sphere centered at a single point, that is, the SUVmax (SUVpeak ), the minimum SUV (SUVmin ), and the intensity of LAT1 expression (maximum and minimum LAT1 expressions) were investigated. RESULTS: Weak correlations were identified between SUVmax and LAT1 maximum score, SUVmin and LAT1 maximum score, and SUVmin and LAT1 minimum score (ρ = 0.427, 0.362, and 0.330, respectively). SUVmax and LAT1 minimum score, SUVpeak and LAT1 maximum score, and SUVpeak and LAT1 minimum score demonstrated moderate correlations (ρ = 0.535, 0.556, and 0.661, respectively). Boron neutron capture therapy (BNCT) was performed in 2 of the 4 patients with discrepancies between 18 F-FBPA accumulation and intensity of LAT1 expression, and the intensity of LAT1 expression was a better predictor of treatment response. CONCLUSION: 18 F-FBPA accumulation and the intensity of LAT1 expression demonstrated a moderate correlation; however, LAT1 expression may be a better predictor of treatment response of BNCT in patients with discrepancies.

Correction: Imamichi et al. Extracellular Release of HMGB1 as an Early Potential Biomarker for the Therapeutic Response in a Xenograft Model of Boron Neutron Capture Therapy. Biology 2022, 11, 420.

In the original publication [...].

Relative biological effectiveness for epithermal neutron beam contaminated with fast neutrons in the linear accelerator-based boron neutron capture therapy system coupled to a solid-state lithium target.

This study aimed to quantify the relative biological effectiveness (RBE) for epithermal neutron beam contaminated with fast neutrons in the accelerator-based boron neutron capture therapy (BNCT) system coupled to a solid-state lithium target. The experiments were performed in National Cancer Center Hospital (NCCH), Tokyo, Japan. Neutron irradiation with the system provided by Cancer Intelligence Care Systems (CICS), Inc. was performed. X-ray irradiation, which was assigned as the reference group, was also performed using a medical linear accelerator (LINAC) equipped in NCCH. The four cell lines (SAS, SCCVII, U87-MG and NB1RGB) were utilized to quantify RBE value for the neutron beam. Before both of those irradiations, all cells were collected and dispensed into vials. The doses of 10% cell surviving fraction (SF) (D10) were calculated by LQ model fitting. All cell experiments were conducted in triplicate at least. Because the system provides not only neutrons, but gamma-rays, the contribution from the gamma-rays to the survival fraction were subtracted in this study. D10 value of SAS, SCCVII, U87-MG and NB1RGB for the neutron beam was 4.26, 4.08, 5.81 and 2.72 Gy, respectively, while that acquired by the X-ray irradiation was 6.34, 7.21, 7.12 and 5.49 Gy, respectively. Comparison of both of the D10 values, RBE value of SAS, SCCVII, U87-MG and NB1RGB for the neutron beam was calculated as 1.7, 2.2, 1.3 and 2.5, respectively, and the average RBE value was 1.9. This study investigated RBE of the epithermal neutron beam contaminated with fast neutrons in the accelerator-based BNCT system coupled to a solid-state lithium target.

Treatment planning comparison of high-dose-rate brachytherapy vs. robotic and conventional stereotactic body radiotherapy for ultrahypofractionated treatment of prostate cancer.

Background and purpose: Ultrahypofractionated radiation therapy is increasingly used in the treatment of prostate cancer. High-dose-rate brachytherapy (HDR-BT) and stereotactic body radiotherapy (SBRT) are representative methods of ultrahypofractionation. This study was performed to compare clinically applied treatment plans for patients who had been treated using HDR-BT vs. conventional or robotic SBRT. Materials and methods: Calculated dose-volume indices between HDR-BT without a perirectal spacer (n = 20), robotic SBRT without a spacer (n = 40), and conventional (non-robotic) SBRT with a spacer (n = 40) were compared. Percentages against the prescription dose regarding the planning target volume (PTV), bladder, rectum, and urethra were statistically compared. Results: The D50% of the PTV with HDR-BT (140.5% ± 4.9%) was significantly higher than that with robotic or conventional SBRT (116.2% ± 1.6%, 101.0% ± 0.4%, p < 0.01). The D2cm3 of the bladder with HDR-BT (65.6% ± 6.4%) was significantly lower than those with SBRT (105.3% ± 2.9%, 98.0% ± 1.3%, p < 0.01). The D2cm3 of the rectum with HDR-BT (60.6% ± 6.2%) was also significantly lower than those with SBRT (85.1% ± 8.8%, 70.4% ± 9.6%, p < 0.01). By contrast, the D0.1cm3 of the urethra with HDR-BT (117.1% ± 3.6%) was significantly higher than those with SBRT (100.2% ± 0.7%, 104.5% ± 0.6%, p < 0.01). Conclusions: HDR-BT could administer a higher dose to the PTV and a lower dose to the bladder and rectum, at the cost of a slightly higher dose to the urethra compared with SBRT.

Prognostic factors associated with the transition in treatment methods for brain metastases from colorectal cancer.

BACKGROUND: Treatment of brain metastases (BMs) from colorectal cancer (CRC) has transitioned with the expansion of indications for stereotactic radiotherapy. Our study aimed to assess changes in prognosis and prognostic factors associated with changes in treatment for BMs from CRC. METHODS: We retrospectively surveyed treatments for and outcomes of BMs from CRC in 208 patients treated during 1997-2018. Patients were divided into two groups according to time of BM diagnosis, i.e., 1997-2013 ("first period") and 2014-2018 ("second period"). We compared overall survival between the periods and assessed how the transition impacted prognostic factors affecting overall survival, including the following prognostic factors such as Karnofsky performance status (KPS), volume-related factors (BM number and diameter), and BM treatment modalities as covariates. RESULTS: Of the 208 patients, 147 were treated in the first period and 61 in the second period. Whole-brain radiotherapy use decreased from 67 to 39% in the second period, and stereotactic radiotherapy use increased from 30 to 62%. Median survival after BM diagnosis improved from 6.1 to 8.5 months (p = 0.0272). Multivariate analysis revealed KPS, control of primary tumor, stereotactic radiotherapy use, and chemotherapy history as independent prognostic factors during the entire observation period. Hazard ratios of KPS, primary tumor control, and stereotactic radiotherapy were higher in the second period, whereas prognostic impact of chemotherapy history before BM diagnosis was similar in both periods. CONCLUSION: Overall survival of patients with BMs from CRC improved since 2014, which can be attributed to advances in chemotherapy and the more widespread use of stereotactic radiotherapy.

Impact of interstitial lung abnormality on survival after adjuvant durvalumab with chemoradiotherapy for locally advanced non-small cell lung cancer.

INTRODUCTION: Concurrent chemoradiotherapy (CCRT) has been the standard of care for patients with locally advanced non-small cell lung cancer (LA-NSCLC). BACKGROUND AND PURPOSE: The results of the PACIFIC trial established the use of consolidative durvalumab after concurrent chemoradiotherapy (CCRT) as the standard of care for patients with locally advanced non-small cell lung cancer (LA-NSCLC). A subgroup analysis of the PACIFIC trial reported a better progression-free survival (PFS) in Asians. Although real-world data on LA-NSCLC patients who received CCRT plus durvalumab have been reported, there have been few large-scale reports on Asians. In this study, we investigated prognostic factors in the largest real-world data set in Asia of only Japanese LA-NSCLC patients treated with CCRT plus durvalumab. MATERIALS AND METHODS: One hundred and thirteen LA-NSCLC patients who received definitive CCRT and consolidative durvalumab at our institution between May 2018 and April 2021 were analyzed. Overall survival (OS), cause-specific survival (CSS), PFS, distant metastasis-free survival (DMFS), and in-field progression-free survival (IFPFS) were investigated as treatment outcomes using competing risk analyses. RESULTS: During a median follow-up of 24 months (range, 5-47) after the initiation of durvalumab therapy, 31 patients died, of whom 23 died of lung cancer. In the multivariate analysis, the pretreatment factors that correlated with OS were ILA scores, adenocarcinoma, and performance status at the initiation of durvalumab. Furthermore, ILA score and programmed cell death ligand 1 (PD-L1) tumor proportion score (TPS) ≥ 1 % were significantly correlated with CSS, and PD-L1 TPS ≥ 1 % was significantly correlated with PFS and IFPFS. CONCLUSION: Pretreatment ILA, adenocarcinoma, and performance status may have an impact on OS of LA-NSCLC patients receiving CCRT plus durvalumab.

Phase I/II prospective clinical trial for the hybrid of intracavitary and interstitial brachytherapy for locally advanced uterine cervical cancer.

OBJECTIVE: The purposes of this trial were to demonstrate the feasibility and effectiveness of the hybrid of intracavitary and interstitial brachytherapy (HBT) for locally advanced cervical cancer patients in the phase I/II prospective clinical trial. METHODS: Patients with FIGO stage IB2-IVA uterine cervical cancer pretreatment width of which was ≥5 cm measured by magnetic resonance imaging were eligible for this clinical trial. The protocol therapy included 30-30.6 Gy in 15-17 fractions of whole pelvic radiotherapy concurrent with weekly CDDP, followed by 24 Gy in 4 fractions of HBT and pelvic radiotherapy with a central shield up to 50-50.4 Gy in 25-28 fractions. The primary endpoint of phase II part was 2-year pelvic progression-free survival (PPFS) rate higher than historical control of 64%. RESULTS: Between October 2015 and October 2019, 73 patients were enrolled in the initial registration and 52 patients proceeded to the secondary registration. With the median follow-up period of 37.3 months (range, 13.9-52.9 months), the 2- PPFS was 80.7% (90% confidence interval [CI]=69.7%-88%). Because the lower range of 90% CI of 2-year PPFS was 69.7%, which was higher than the historical control ICBT data of 64%, therefore, the primary endpoint of this study was met. CONCLUSION: The effectiveness of HBT were demonstrated by a prospective clinical study. Because the dose goal determined in the protocol was lower than 85 Gy, there is room in improvement for local control. A higher dose might have been needed for tumors with poor responses.

Analyzing spatial distribution between 18F-fluorodeoxyglucose and 18F-boronophenylalanine positron emission tomography to investigate selection indicators for boron neutron capture therapy.

BACKGROUND: 18F-FDG PET is often utilized to determine BNCT selection due to the limited availability of 18F-BPA PET, which is performed by synthesizing 18F into the boron drug used for BNCT, although the uptake mechanisms between those are different. Additionally, only a few non-spatial point parameters, such as maximum SUV (SUVmax), have reported a correlation between those in previous studies. This study aimed to investigate the spatial accumulation pattern between those PET images in tumors, which would be expected to either show higher uptake on 18F-BPA PET or be utilized in clinical, to verify whether 18F-FDG PET could be used as a selection indicator for BNCT. METHODS: A total of 27 patients with 30 lesions (11 squamous cell carcinoma, 9 melanoma, and 10 rhabdomyosarcoma) who received 18F-FDG and 18F-BPA PET within 2 weeks were enrolled in this study. The ratio of metabolic tumor volumes (MTVs) to GTV, histogram indices (skewness/kurtosis), and the correlation of total lesion activity (TLA) and non-spatial point parameters (SUVmax, SUVpeak, SUVmin, maximum tumor-to-normal tissue ratio (Tmax/N), and Tmin/N) were evaluated. After local rigid registration between those images, distances of locations at SUVmax and the center of mass with MTVs on each image and similarity indices were also assessed along its coordinate. RESULTS: In addition to SUVmax, SUVpeak, and Tmax/N, significant correlations were found in TLA. The mean distance in SUVmax was [Formula: see text] and significantly longer than that in the center of mass with MTVs. The ratio of MTVs to GTV, skewness, and kurtosis were not significantly different. However, the similarities of MTVs were considerably low. The similarity indices of Dice similarity coefficient, Jaccard coefficient, and mean distance to agreement for MTV40 were [Formula: see text], [Formula: see text], and [Formula: see text] cm, respectively. Furthermore, it was worse in MTV50. In addition, spatial accumulation patterns varied in cancer types. CONCLUSIONS: Spatial accumulation patterns in tumors showed low similarity between 18F-FDG and 18F-BPA PET, although the various non-spatial point parameters were correlated. In addition, the spatial accumulation patterns were considerably different in cancer types. Therefore, the selection for BNCT using 18F-FDG PET should be compared carefully with using 18F-FBPA PET.

Functional peptide-mediated plastid transformation in tobacco, rice, and kenaf.

In plant engineering, plastid transformation is more advantageous than nuclear transformation because it results in high levels of protein expression from multiple genome copies per cell and is unaffected by gene silencing. The common plastid transformation methods are biolistic bombardment that requires special instruments and PEG-mediated transformation that is only applicable to protoplast cells. Here, we aimed to establish a new plastid transformation method in tobacco, rice, and kenaf using a biocompatible fusion peptide as a carrier to deliver DNA into plastids. We used a fusion peptide, KH-AtOEP34, comprising a polycationic DNA-binding peptide (KH) and a plastid-targeting peptide (AtOEP34) to successfully deliver and integrate construct DNA into plastid DNA (ptDNA) via homologous recombination. We obtained transformants in each species using selection with spectinomycin/streptomycin and the corresponding resistance gene aadA. The constructs remained in ptDNA for several months after introduction even under non-selective condition. The transformants normally flowered and are fertile in most cases. The offspring of the transformants (the T1 generation) retained the integrated construct DNA in their ptDNA, as indicated by PCR and DNA blotting, and expressed GFP in plastids from the integrated construct DNA. In summary, we successfully used the fusion peptide method for integration of foreign DNA in tobacco, rice, and kenaf ptDNA, and the integrated DNA was transmitted to the next generations. Whereas optimization is necessary to obtain homoplasmic plastid transformants that enable stable heterologous expression of genes, the plastid transformation method shown here is a novel nanomaterial-based approach distinct from the conventional methods, and we propose that this easy method could be used to target a wide variety of plants.

An Asian multi-national, multi-institutional, retrospective study on image-guided brachytherapy in cervical adenocarcinoma and adenosquamous carcinoma.

Purpose: There are limited reports on outcomes of three-dimensional image-guided brachytherapy (3D-IGBT) for cervical adenocarcinoma in Asia. In a multi-institutional retrospective study, we assessed the clinical outcomes of three-dimensional image-guided brachytherapy for cervical adenocarcinoma or adenosquamous carcinoma (CA/CAC) in Asian countries. Material and methods: Patients who had undergone definitive radiation therapy/concurrent chemoradiotherapy for untreated cervical cancer between 2000 and 2016 were registered. Those who had undergone 3D-IGBT for histologically proven CA/CAC were included. Data on patients' characteristics and treatment were collected, including tumor reduction rate (defined as a percentage of reduction in tumor size before brachytherapy compared with that at diagnosis) and high-risk clinical target volume D90. Overall survival (OS), local control (LC), and progression-free survival (PFS) rates were calculated using Kaplan-Meier method. Late toxicities were assessed using common terminology criteria for adverse events version 4.0. Results: Anonymized data of 498 patients were collected. Of the 498 patients, 36 patients met inclusion criteria. The median follow-up period was 39 months. The 3-year OS, LC, and PFS rates were 68.4%, 68.5%, and 44.4%, respectively. After treatment, five patients had tumor re-growth without complete disappearance of the tumor. Two patients developed grade 3 vaginal toxicity or grade 4 rectal toxicity; none developed other severe late toxicities. A tumor reduction rate of > 26.3% was the only significant factor in multivariate analyses, and was associated with significantly better OS (p = 0.018), LC (p = 0.022), and PFS (p = 0.013). There were no significant trends in local control or dose to high-risk clinical target volume D90. Conclusions: LC rate of CA/CAC was insufficient despite 3D-IGBT. Meanwhile, tumor reduction rate was associated with LC, OS, and PFS rates. Therefore, CA/CAC may require a different treatment strategy than that applied in cervical squamous cell carcinoma.

Technical report: a high-dose-rate interstitial brachytherapy boost for residual sinonasal undifferentiated carcinoma.

Sinonasal undifferentiated carcinoma (SNUC) is a highly aggressive and uncommon neoplasm that arises from the mucosa of the nasal cavity or paranasal sinuses. The multidisciplinary approach that includes surgery, radiation therapy (RT), and chemotherapy has been proven to improve survival rates. However, there is no established evidence for the efficacy of further (boost) irradiation following definitive RT in SNUC patients with residual primary tumor. We describe a successful case of a patient with SNUC who had an uncontrolled primary tumor following induction chemotherapy and radical concurrent chemoradiotherapy (CCRT) and underwent a high-dose-rate interstitial brachytherapy (HDR-ISBT) boost. A 75-year-old Japanese woman with unresectable locally advanced SNUC (LA-SNUC) received induction chemotherapy followed by radical CCRT. However, because the residual primary tumor was evident after planned external beam RT, she underwent an HDR-ISBT boost, and the tumor decreased significantly. A complete response (the Response Evaluation Criteria in Solid Tumors, ver. 1.1) was achieved 2 months after brachytherapy, and the patient has been disease-free for 2 years following treatment initiation. In conclusion, an HDR-ISBT boost can be a safe and effective treatment option in patients with residual and inoperable LA-SNUC in the maxillary sinus after initial RT.

SpaceOAR hydrogel spacer in interstitial brachytherapy for intrapelvic recurrent endometrial cancer.

Objective: We report the use of SpaceOAR hydrogel spacer in interstitial brachytherapy (ISBT) for a patient with intrapelvic recurrent endometrial cancer (EC). Methods and materials: A 59-year-old female patient was diagnosed with intrapelvic recurrence of EC after a definitive surgery. Despite administration of adjuvant chemotherapy, the recurrent tumour in the right para-rectal fossa increased in size. Salvage radiotherapy, including external beam radiotherapy followed by ISBT boost, was planned. We planned to inject SpaceOAR between the tumour and rectum to reduce the rectal dose in ISBT; transrectal ultrasound-guided SpaceOAR injection was performed using needle applicator insertion. This was followed by computed tomography-based image-guided brachytherapy. Results: The use of SpaceOAR allowed us to achieved both a higher dose for the clinical target volume and a lower dose for the rectum. Furthermore, no ISBT-related complications or acute toxicities were observed. Conclusions: The preliminary results suggest that SpaceOAR could be effective in increasing the efficacy of ISBT for intrapelvic recurrent EC, while reducing the associated complications.

Clinical impact of p16 positivity in nasopharyngeal carcinoma.

Purpose: The clinical characteristics and prognosis of HPV-related nasopharyngeal cancer (NPC) remain controversial. The relationship between p16 status and outcome was retrospectively investigated in the NPC patients. Materials and Methods: Between May 2009 and May 2019, 81 NPC patients who received definitive radiation therapy, in a hospital in Japan, were identified and the prognosis was investigated. p16, p53, and Epstein-Barr virus (EBV) status were assessed. Also, circumferential tumor extent in the nasopharyngeal cavity was assessed on a 5-point scale. Results: Nine and 72 patients were p16-positive and p16-negative, respectively. Fewer patients were EBV-encoded RNA in situ hybridization (EBER-ISH)-positive in the p16-positive group than in the p16-negative group (p < .01). Seventy-five patients were nonkeratinizing NPCs, and six patients were keratinizing NPCs. There were two p16-positive patients among the keratinizing NPCs.The mean circumferential tumor extent scores of 16-positive and p16-negative NPCs were 4.2 and 3.2, respectively with a statistically significant difference (p = .02). Two-year progression-free survival (PFS) of p16-positive and p16-negative patients undergoing chemoradiation therapy were 100% and 69%, respectively (p = .13). Conclusion: In this study conducted in Japan, p16-positive NPC patients are minor but not very low, and the proportion of keratinizing NPCs was small. p16-positive NPCs were seen both in keratinizing and nonkeratinizing NPCs. P16-positive NPC had a tendency of better PFS than p16-negative NPC. This better prognosis might be due to the higher radiosensitivity of the p16-positive cell. Additionally, p16-positive NPCs seemed to spread more extensively in circumference along the nasopharyngeal mucosa than p16-negative NPCs.

Clinical adoption patterns of 0.35 Tesla MR-guided radiation therapy in Europe and Asia.

BACKGROUND: Magnetic resonance-guided radiotherapy (MRgRT) utilization is rapidly expanding, driven by advanced capabilities including better soft tissue imaging, continuous intrafraction target visualization, automatic triggered beam delivery, and the availability of on-table adaptive replanning. Our objective was to describe patterns of 0.35 Tesla (T)-MRgRT utilization in Europe and Asia among early adopters of this novel technology. METHODS: Anonymized administrative data from all 0.35T-MRgRT treatment systems in Europe and Asia were extracted for patients who completed treatment from 2015 to 2020. Detailed treatment information was analyzed for all MR-linear accelerators (linac) and -cobalt systems. RESULTS: From 2015 through the end of 2020, there were 5796 completed treatment courses delivered in 46,389 individual fractions. 23.5% of fractions were adapted. Ultra-hypofractionated (UHfx) dose schedules (1-5 fractions) were delivered for 63.5% of courses, with 57.8% of UHfx fractions adapted on-table. The most commonly treated tumor types were prostate (23.5%), liver (14.5%), lung (12.3%), pancreas (11.2%), and breast (8.0%), with increasing compound annual growth rates (CAGRs) in numbers of courses from 2015 through 2020 (pancreas: 157.1%; prostate: 120.9%; lung: 136.0%; liver: 134.2%). CONCLUSIONS: This is the first comprehensive study reporting patterns of utilization among early adopters of a 0.35T-MRgRT system in Europe and Asia. Intrafraction MR image-guidance, advanced motion management, and increasing adoption of on-table adaptive RT have accelerated a transition to UHfx regimens. MRgRT has been predominantly used to treat tumors in the upper abdomen, pelvis and lungs, and increasingly with adaptive replanning, which is a radical departure from legacy radiotherapy practices.

Practical guidelines of online MR-guided adaptive radiotherapy.

The first magnetic resonance (MR)-guided radiotherapy system in Japan was installed in May 2017. Implementation of online MR-guided adaptive radiotherapy (MRgART) began in February 2018. Online MRgART offers greater treatment accuracy owing to the high soft-tissue contrast in MR-images (MRI), compared to that in X-ray imaging. The Japanese Society for Magnetic Resonance in Medicine (JSMRM), Japan Society of Medical Physics (JSMP), Japan Radiological Society (JRS), Japanese Society of Radiological Technology (JSRT), and Japanese Society for Radiation Oncology (JASTRO) jointly established the comprehensive practical guidelines for online MRgART. These guidelines propose the essential requirements for clinical implementation of online MRgART with respect to equipment, personnel, institutional environment, practice guidance, and quality assurance/quality control (QA/QC). The minimum requirements for related equipment and QA/QC tools, recommendations for safe operation of MRI system, and the implementation system are described. The accuracy of monitor chamber and detector in dose measurements should be confirmed because of the presence of magnetic field. The ionization chamber should be MR-compatible. Non-MR-compatible devices should be used in an area that is not affected by the static magnetic field (outside the five Gauss line), and their operation should be checked to ensure that they do not affect the MR image quality. Dose verification should be performed using an independent dose verification system that has been confirmed to be reliable through commissioning. This guideline proposes the checklists to ensure the safety of online MRgART. Successful clinical implementation of online MRgART requires close collaboration between physician, radiological technologist, nurse, and medical physicist.