Synthetic Low-Energy Monochromatic Image Generation in Single-Energy Computed Tomography System Using a Transformer-Based Deep Learning Model.

While dual-energy computed tomography (DECT) technology introduces energy-specific information in clinical practice, single-energy CT (SECT) is predominantly used, limiting the number of people who can benefit from DECT. This study proposed a novel method to generate synthetic low-energy virtual monochromatic images at 50 keV (sVMI50keV) from SECT images using a transformer-based deep learning model, SwinUNETR. Data were obtained from 85 patients who underwent head and neck radiotherapy. Among these, the model was built using data from 70 patients for whom only DECT images were available. The remaining 15 patients, for whom both DECT and SECT images were available, were used to predict from the actual SECT images. We used the SwinUNETR model to generate sVMI50keV. The image quality was evaluated, and the results were compared with those of the convolutional neural network-based model, Unet. The mean absolute errors from the true VMI50keV were 36.5 ± 4.9 and 33.0 ± 4.4 Hounsfield units for Unet and SwinUNETR, respectively. SwinUNETR yielded smaller errors in tissue attenuation values compared with those of Unet. The contrast changes in sVMI50keV generated by SwinUNETR from SECT were closer to those of DECT-derived VMI50keV than the contrast changes in Unet-generated sVMI50keV. This study demonstrated the potential of transformer-based models for generating synthetic low-energy VMIs from SECT images, thereby improving the image quality of head and neck cancer imaging. It provides a practical and feasible solution to obtain low-energy VMIs from SECT data that can benefit a large number of facilities and patients without access to DECT technology.

Feasibility of a portable respiratory training system with a gyroscope sensor.

OBJECTIVES: A portable respiratory training system with a gyroscope sensor (GRTS) was developed and the feasibility of respiratory training was evaluated. METHODS: Simulated respiratory waveforms from a respiratory motion phantom and actual respirator waveforms from volunteers were acquired using the GRTS and Respiratory Gating for Scanners system (RGSC). Respiratory training was evaluated by comparing the stability and reproducibility of respiratory waveforms from patients undergoing liver stereotactic body radiation therapy, with and without the GRTS. The stability and reproducibility of respiratory waveforms were assessed by root mean square error and gold marker placement-based success rate of expiratory breath-hold, respectively. RESULTS: The absolute mean difference for sinusoidal waveforms between the GRTS and RGSC was 2.1%. Among volunteers, the mean percentages of errors within ±15% of the respiratory waveforms acquired by the GRTS and RGSC were 95.5% for free breathing and 80.7% for expiratory breath-hold. The mean root mean square error and success rate of expiratory breath-hold (standard deviation) with and without the GRTS were 0.65 (0.24) and 0.88 (0.89) cm, and 91.0% (6.9) and 89.1% (11.6), respectively. CONCLUSIONS: Respiratory waveforms acquired by the GRTS exhibit good agreement with waveforms acquired by the RGSC. Respiratory training with the GRTS reduces inter-patient variability in respiratory waveforms, thereby improving the success of expiratory breath-hold liver stereotactic body radiation therapy. ADVANCES IN KNOWLEDGE: A respiratory training system with a gyroscope sensor is inexpensive and portabl, making it ideal for respiratory training. This is the first report concerning clinical implementation of a respiratory training system.

Risk of thoracic soft tissue sarcoma after breast cancer radiotherapy: a population-based cohort study in Osaka, Japan.

Postoperative radiotherapy for breast cancer reportedly increases the risk of thoracic soft tissue sarcomas, particularly angiosarcomas; however, the risk in the Japanese population remains unknown. Therefore, this study aimed to investigate the incidence of thoracic soft tissue sarcoma among patients with breast cancer in Japan and determine its association with radiotherapy. This retrospective cohort study used data from the population-based cancer registry of the Osaka Prefecture. The inclusion criteria were female sex, age 20-84 years, diagnosis of breast cancer between 1990 and 2010, no supraclavicular lymph node or distant metastasis, underwent surgery and survived for at least 1 year. The primary outcome was the occurrence of thoracic soft tissue sarcomas 1 year or later after breast cancer diagnosis. Among the 13 762 patients who received radiotherapy, 15 developed thoracic soft tissue sarcomas (nine angiosarcomas and six other sarcomas), with a median time of 7.7 years (interquartile range, 4.0-8.6 years) after breast cancer diagnosis. Among the 27 658 patients who did not receive radiotherapy, four developed thoracic soft tissue sarcomas (three angiosarcomas and one other sarcoma), with a median time of 11.6 years after diagnosis. The 10-year cumulative incidence was higher in the radiotherapy cohort than in the non-radiotherapy cohort (0.087 vs. 0.0036%, P < 0.001). Poisson regression analysis revealed that radiotherapy increased the risk of thoracic soft tissue sarcoma (relative risk, 6.8; 95% confidence interval, 2.4-24.4). Thus, although rare, breast cancer radiotherapy is associated with an increased risk of thoracic soft tissue sarcoma in the Japanese population.

Safety and Feasibility of Combining On-Demand Selective Locoregional Treatment with First-Line Atezolizumab Plus Bevacizumab for Patients with Unresectable Hepatocellular Carcinoma.

Various locoregional treatments for localized hepatocellular carcinoma (HCC) have been developed. This retrospective study investigated the safety and feasibility of combining on-demand selective locoregional treatment for residual lesions after tumor shrinkage (complete response [CR] oriented) or for solitary or few drug-resistant lesions (progressive disease (PD) salvage) with first-line atezolizumab plus bevacizumab (atezo/bev) for unresectable HCC. Twenty-nine patients with unresectable HCC were included. Fourteen locoregional treatments were performed (CR oriented, 7; PD salvage, 7) in ten patients in the combination-therapy group. All patients in the combination-therapy group successfully achieved a CR or PD salvage status after the planned locoregional treatment. The objective response rate of the combination-therapy group (80.0%) was higher than that of the atezo/bev alone group (21.1%; p = 0.005). Progression-free survival (PFS) and overall survival (OS) were longer in the combination group (medians for PFS and OS not reached) than in the atezo/bev alone group (median PFS, 7.4 months; median OS, 19.8 months) (PFS, p = 0.004; OS, p < 0.001). The albumin-bilirubin score did not change, and no severe complications occurred after locoregional treatment. When performed in a minimally invasive manner, on-demand selective locoregional treatment combined with first-line atezo/bev could be safe and feasible for unresectable HCC.

The effects of distance between the imaging isocenter and brain center on the image quality of cone-beam computed tomography for brain stereotactic irradiation.

In linear accelerator-based stereotactic irradiation (STI) for brain metastasis, cone-beam computed tomography (CBCT) image quality is essential for ensuring precise patient setup and tumor localization. However, CBCT images may be degraded by the deviation of the CBCT isocenter from the brain center. This study aims to investigate the effects of the distance from the brain center to the CBCT isocenter (DBI) on the image quality in STI. An anthropomorphic phantom was scanned with varying DBI in right, anterior, superior, and inferior directions. Thirty patients undergoing STI were prospectively recruited. Objective metrics, utilizing regions of interest included contrast-to-noise ratio (CNR) at the centrum semiovale, lateral ventricle, and basal ganglia levels, gray and white matter noise at the basal ganglia level, artifact index (AI), and nonuniformity (NU). Two radiation oncologists assessed subjective metrics. In this phantom study, objective measures indicated a degradation in image quality for non-zero DBI. In this patient study, there were significant correlations between the CNR at the centrum semiovale and lateral ventricle levels (rs = - 0.79 and - 0.77, respectively), gray matter noise (rs = 0.52), AI (rs = 0.72), and NU (rs = 0.91) and DBI. However, no significant correlations were observed between the CNR at the basal ganglia level, white matter noise, and subjective metrics and DBI (rs < ± 0.3). Our results demonstrate the effects of DBI on contrast, noise, artifacts in the posterior fossa, and uniformity of CBCT images in STI. Aligning the CBCT isocenter with the brain center can aid in improving image quality.

Re-irradiation for isolated neck recurrence in head and neck tumor: impact of rN category.

Unresectable, isolated lymph node recurrence after radiotherapy is rare but a candidate for re-irradiation. However, severe toxicity is anticipated. Therefore, this study aimed to explore the efficacy and toxicity of re-irradiation in isolated lymph node recurrence of head and neck lesions. We analyzed 46 patients who received re-irradiation for lymph node recurrence without local progression. The primary tumor sites included the oral cavity in 17 patients, the hypopharynx in 12, the oropharynx in seven, the larynx in three, the nasopharynx in two, and other sites. During a median follow-up time of 10 months, the median survival time was 10.6 months, and the 1-year overall survival rate was 45.5%. The 1-year local control and progression-free survival rates were 49.8% and 39.3%, respectively. According to univariate analysis, age (≥ 65 years), the interval between treatment (≥ 12 months), rN category (rN1), and gross tumor volume (GTV < 25 cm3) were predisposing factors for better survival. In the multivariate analysis, the rN category and interval were identified as statistically significant predictors. Late toxicity grade ≥ 3 occurred in four patients (8.6%). These were all Grade 5 carotid blowout syndrome, which associated with tumor invasion of the carotid artery and/ or high doses administration for the carotid artery. Small-volume rN1 tumor that recur after a longer interval is a feasible candidate for re-irradiation. However, strict patient selection and meticulous care for the carotid are required.

Artificial intelligence-based image-domain material decomposition in single-energy computed tomography for head and neck cancer.

PURPOSE: While dual-energy computed tomography (DECT) images provide clinically useful information than single-energy CT (SECT), SECT remains the most widely used CT system globally, and only a few institutions can use DECT. This study aimed to establish an artificial intelligence (AI)-based image-domain material decomposition technique using multiple keV-output learning of virtual monochromatic images (VMIs) to create DECT-equivalent images from SECT images. METHODS: This study involved 82 patients with head and neck cancer. Of these, the AI model was built with data from the 67 patients with only DECT scans, while 15 patients with both SECT and DECT scans were used for SECT testing. Our AI model generated VMI50keV and VMI100keV from VMI70keV equivalent to 120-kVp SECT images. We introduced a loss function for material density images (MDIs) in addition to the loss for VMIs. For comparison, we trained the same model with the loss for VMIs only. DECT-equivalent images were generated from SECT images and compared with the true DECT images. RESULTS: The prediction time was 5.4 s per patient. The proposed method with the MDI loss function quantitatively provided more accurate DECT-equivalent images than the model trained with the loss for VMIs only. Using real 120-kVp SECT images, the trained model produced precise DECT images of excellent quality. CONCLUSION: In this study, we developed an AI-based material decomposition approach for head and neck cancer patients by introducing the loss function for MDIs via multiple keV-output learning. Our results suggest the feasibility of AI-based image-domain material decomposition in a conventional SECT system without a DECT scanner.

Impact of magnetic resonance imaging-related geometric distortion of dose distribution in fractionated stereotactic radiotherapy in patients with brain metastases.

PURPOSE: The geometric distortion related to magnetic resonance (MR) imaging in a diagnostic radiology (MRDR) and radiotherapy (MRRT) setup is evaluated, and the dosimetric impact of MR distortion on fractionated stereotactic radiotherapy (FSRT) in patients with brain metastases is simulated. MATERIALS AND METHODS: An anthropomorphic skull phantom was scanned using a 1.5­T MR scanner, and the magnitude of MR distortion was calculated with (MRDR-DC and MRRT-DC) and without (MRDR-nDC and MRRT-nDC) distortion-correction algorithms. Automated noncoplanar volumetric modulated arc therapy (HyperArc, HA; Varian Medical Systems, Palo Alto, CA, USA) plans were generated for 53 patients with 186 brain metastases. The MR distortion at each gross tumor volume (GTV) was calculated using the distance between the center of the GTV and the MR image isocenter (MIC) and the quadratic regression curve derived from the phantom study (MRRT-DC and MRRT-nDC). Subsequently, the radiation isocenter of the HA plans was shifted according to the MR distortion at each GTV (HADC and HAnDC). RESULTS: The median MR distortions were approximately 0.1 mm when the distance from the MIC was < 30 mm, whereas the median distortion varied widely when the distance was > 60 mm (0.23, 0.47, 0.37, and 0.57 mm in MRDR-DC, MRDR-nDC, MRRT-DC, and MRRT-nDC, respectively). The dose to the 98% of the GTV volume (D98%) decreased as the distance from the MIC increased. In the HADC plans, the relative dose difference of D98% was less than 5% when the GTV was located within 70 mm from the MIC, whereas the underdose of GTV exceeded 5% when it was 48 mm (-26.5% at maximum) away from the MIC in the HAnDC plans. CONCLUSION: Use of a distortion-correction algorithm in the studied MR diagnoses is essential, and the dosimetric impact of MR distortion is not negligible, particularly for tumors located far away from the MIC.

Outcomes in patients with high- and very high-risk localized prostate cancer treated with definitive IMRT and long-term hormone therapy.

BACKGROUND: The aim of this study was to evaluate the effectiveness of intensity-modulated radiation therapy in combination with long-term androgen deprivation therapy for high-risk and very high-risk localized prostate cancer while also investigating factors associated with the therapeutic effect. METHODS: Men who fulfilled criteria for the National Comprehensive Cancer Network high-risk or very high-risk localized prostate cancer and were treated with definitive intensity-modulated radiation therapy (74-78 Gy) of the prostate and the seminal vesicle combined with androgen deprivation therapy in our institution from 2007 to 2016 were identified (n = 197). In principle, patients received androgen deprivation therapy for 3-6 months before radiation, concurrently, and for 2 years after completion of intensity-modulated radiation therapy. RESULTS: The median follow-up period was 96 months. The 5-year and 10-year overall survival rates in the overall population were 96.9% and 89.3%, respectively. The 5-year and 10-year cumulative incidence rates of biochemical failure were 2.5% and 16.3% in the high-risk group, and 8.6% and 32.0% in the very high-risk group, respectively, indicating a significant difference between the two groups (P = 0.023). Grade Group 5 and younger age (cutoff: 70 years old) were independent predictors of recurrence (P = 0.016 and 0.017, respectively). Patients exhibiting biochemical failure within <18 months after completion of androgen deprivation therapy displayed an increased risk of cancer-specific mortality (P = 0.039) when contrasted with those who had a longer interval to biochemical failure. CONCLUSIONS: Patients with the National Comprehensive Cancer Network very high-risk prostate cancer, particularly those with Grade Group 5 and younger age, showed worse outcomes following intensity-modulated radiation therapy and long-term androgen deprivation therapy.

Dual-energy computed tomography-based iodine concentration as a predictor of histopathological response to preoperative chemoradiotherapy for pancreatic cancer.

To explore predictors of the histopathological response to preoperative chemoradiotherapy (CRT) in patients with pancreatic cancer (PC) using dual-energy computed tomography-reconstructed images. This retrospective study divided 40 patients who had undergone preoperative CRT (50-60 Gy in 25 fractions) followed by surgical resection into two groups: the response group (Grades II, III and IV, evaluated from surgical specimens) and the nonresponse group (Grades Ia and Ib). The computed tomography number [in Hounsfield units (HUs)] and iodine concentration (IC) were measured at the locations of the aorta, PC and pancreatic parenchyma (PP) in the contrast-enhanced 4D dual-energy computed tomography images. Logistic regression analysis was performed to identify predictors of histopathological response. Univariate analysis did not reveal a significant relation between any parameter and patient characteristics or dosimetric parameters of the treatment plan. The HU and IC values in PP and the differences in HU and IC between the PP and PC (ΔHU and ΔIC, respectively) were significant predictors for distinguishing the response (n = 24) and nonresponse (n = 16) groups (P < 0.05). The IC in PP and ΔIC had a higher area under curve values [0.797 (95% confidence interval, 0.659-0.935) and 0.789 (0.650-0.928), respectively] than HU in PP and ΔHU [0.734 (0.580-0.889) and 0.721 (0.562-0.881), respectively]. The IC value could potentially be used for predicting the histopathological response in patients who have undergone preoperative CRT.

Long-Term Follow-up of a Randomized Controlled Trial on Accelerated Radiation Therapy Versus Standard Fractionated Radiation Therapy for Early Glottic Cancer (JCOG0701A3).

PURPOSE: We previously reported the primary results of JCOG0701, a randomized, multicenter, phase 3, noninferiority trial comparing accelerated fractionation (Ax) to standard fractionation (SF) for early glottic cancer. In the primary results, although the similar efficacy of 3-year progression-free survival and toxicity of Ax compared with SF was observed, the noninferiority of Ax was not confirmed statistically. To evaluate the long-term follow-up results of JCOG0701, we conducted JCOG0701A3 as an ancillary study of JCOG0701. METHODS AND MATERIALS: In JCOG0701, 370 patients were randomly assigned to receive SF of 66 to 70 Gy (33-35 fractions; n = 184) or Ax of 60 to 64.8 Gy (25-27 fractions; n = 186). The data cutoff date for this analysis was in June 2020. Overall survival, progression-free survival, and late adverse events including central nervous system ischemia were analyzed. RESULTS: With a median follow-up period of 7.1 years (range, 0.1-12.4), progression-free survival of the SF and Ax arms were 76.2% and 78.2% at 5 years and 72.7% and 74.8% at 7 years (P = .44). OS of the SF and Ax arms were 92.7% and 89.6% at 5 years and 90.8% and 86.5% at 7 years (P = .92). Among 366 patients with a protocol treatment, the cumulative incidence of late adverse events of the SF and Ax arms were 11.9% and 7.4% at 8 years (hazard ratio, 0.53; 95% CI, 0.28-1.01; P = .06). Central nervous system ischemia of grade 2 or higher was observed in 4.1% for the SF arm and 1.1% for the Ax arm (P = .098). CONCLUSIONS: After long-term follow-up, Ax showed comparable efficacy to SF and a tendency for better safety. Ax may be suitable for early glottic cancer because of its convenience in minimizing treatment time, cost, and labor.

Effect of topical agents on skin surface dose in volumetric modulated arc therapy for head and neck cancer.

In volumetric modulated arc therapy (VMAT), the effect of an increase in skin surface dose due to topical agents might be negligible. We investigated the bolus effects of three types of topical agents in VMAT for head and neck cancer (HNC). Topical agents of different thicknesses (0.1, 0.5 and 2 mm) were prepared. When each topical agent was set, the surface doses were measured for the anterior static field and VMAT, with and without a thermoplastic mask. No significant differences were observed among the three topical agents. For topical agent thicknesses of 0.1, 0.5 and 2 mm, the increases in surface dose for the anterior static field without the thermoplastic mask were 7-9, 30-31 and 81-84%, respectively. With the thermoplastic mask, the corresponding increases were 5, 12-15 and 41-43%, respectively. The increases in surface dose for VMAT without the thermoplastic mask were 5-8, 16-19 and 36-39%, respectively, and those with the thermoplastic mask were 4, 7-10 and 15-19%, respectively. The rate of increase in surface dose with the thermoplastic mask was smaller than that without the thermoplastic mask. The increase in surface dose with topical agents of clinical standard thickness (0.02 mm) was estimated to be 2% with the thermoplastic mask. The increase in surface dose with topical agents in dosimetric simulation, compared with control situation, is not significant in clinical conditions for HNC patients.

Definitive S-1/mitomycin-C chemoradiotherapy for stage II/III anal canal squamous cell carcinoma: a phase I/II dose-finding and single-arm confirmatory study (JCOG0903).

BACKGROUND: Definitive chemoradiotherapy (CRT) with 5-fluorouracil plus mitomycin-C is a standard treatment for stage II/III squamous cell carcinoma of the anal canal (SCCA). We performed this dose-finding and single-arm confirmatory trial of CRT with S-1 plus mitomycin-C to determine the recommended dose (RD) of S-1 and evaluate its efficacy and safety for locally advanced SCCA. METHODS: Patients with clinical stage II/III SCCA (UICC 6th) received CRT comprising mitomycin-C (10 mg/m2 on days 1 and 29) and S-1 (60 mg/m2/day at level 0 and 80 mg/m2/day at level 1 on days 1-14 and 29-42) with concurrent radiotherapy (59.4 Gy). Dose-finding used a 3 + 3 cohort design. The primary endpoint of the confirmatory trial was 3-year event-free survival. The sample size was 65, with one-sided alpha of 5%, power of 80%, and expected and threshold values of 75% and 60%, respectively. RESULTS: Sixty-nine patients (dose-finding, n = 10; confirmatory, n = 59) were enrolled. The RD of S-1 was determined as 80 mg/m2/day. Three-year event-free survival in 63 eligible patients who received the RD was 65.0% (90% confidence interval 54.1-73.9). Three-year overall, progression-free, and colostomy-free survival rates were 87.3%, 85.7%, and 76.2%, respectively; the complete response rate was 81% on central review. Common grade 3/4 acute toxicities were leukopenia (63.1%), neutropenia (40.0%), diarrhea (20.0%), radiation dermatitis (15.4%), and febrile neutropenia (3.1%). No treatment-related deaths occurred. CONCLUSIONS: Although the primary endpoint was not met, S-1/mitomycin-C chemoradiotherapy had an acceptable toxicity profile and favorable 3-year survival and could be a treatment option for locally advanced SCCA. CLINICAL TRIAL INFORMATION: jRCTs031180002.

Dosimetric Comparison of Helical Tomotherapy and HyperArc Treatment Plans for Angiosarcoma of the Scalp.

BACKGROUND/AIM: Angiosarcoma of the scalp (AS) is a rare tumor that has often been treated by total scalp irradiation (TSI). TSI has technical and dosimetric challenges. This study aimed to compare the dosimetric performance of helical tomotherapy (HT) plans with that of HyperArc (HA) plans for TSI in AS. PATIENTS AND METHODS: A planning study was conducted for 11 patients with AS (70 Gy/35 fr). HT and HA planning was performed using TomoHDA and TrueBeam Edge systems, respectively. The performance of three different plans were compared: HT, HA, and HA with half-field beams (HF-HA). The dose distribution and dosimetric parameters for each plan were evaluated. RESULTS: All constraint parameters for the target and organs at risk (OARs) met the goals within acceptable limits for the three techniques. The HA and HF-HA plans provided significantly lower mean brain dose (12.46±2.48 Gy and 8.02±1.48 Gy) than did the HT plan (17.59±3.47 Gy). The doses receiving 0.1 cc of the volume for brainstem and chiasm were significantly lower in the HA and HF-HA plans than those in the HT plan. The HA and HF-HA plans provided a shorter beam-on time (155±3 s and 181±14 s) than did the HT plan (962±221 s). CONCLUSION: The HA plan provided significantly better OARs sparing than the HT plan for TSI in AS and had an advantage to using half-field beams.

Linear accelerator-based stereotactic radiotherapy for brain metastases, including multiple and large lesions, carries a low incidence of acute toxicities: a retrospective analysis.

BACKGROUND: Data on acute toxicities after stereotactic radiotherapy (SRT) for brain metastases, including multiple and large lesions, are lacking. We aimed to evaluate the incidence and nature of toxicities immediately after SRT using a linear accelerator. METHODS: This retrospective study reviewed the medical records of 315 patients with brain metastases treated with SRT at our institution between May 2019 and February 2022. In total, 439 SRT sessions were performed for 2161 brain metastases. The outcome of interest was immediate side effects (ISEs), defined as new or worsening symptoms occurring during SRT or within 14 days after the end of SRT. RESULTS: Grade ≥ 2 and ≥ 3 ISEs occurred in 16 (3.6%) and 7 (1.6%) cases, respectively. Among 63 treatments for 10 or more lesions (range: 10-40), 1 (1.6%) ISE occurred. Among 22 treatments for lesions with a maximum tumor volume of > 10 cc, 2 (9.1%) ISEs occurred. Grade ≥ 3 ISEs included 1, 4, 1, and 1 cases of grade 3 nausea, grade 3 new-onset partial and generalized seizures, grade 3 obstructive hydrocephalus, and grade 5 intracranial hemorrhage, respectively. ISEs were more common in patients with a larger maximum tumor volume, primary sites other than lung and breast cancer, and pre-treatment neurological symptoms. CONCLUSION: SRT using a linear accelerator for brain metastases, including multiple and large lesions, is safe, with a low incidence of ISEs. Serious complications immediately after SRT are rare but possible; therefore, careful follow-up is necessary after treatment initiation.

Improvement of target coverage using automated non-coplanar volumetric modulated arc therapy planning in stereotactic radiotherapy for cervical metastatic spinal tumors.

This study aimed to compare dosimetric parameters for targets and organs at risk (OARs) between volumetric modulated arc therapy (VMAT) and automated VMAT (HyperArc, HA) plans in stereotactic radiotherapy for patients with cervical metastatic spine tumors. VMAT plans were generated for 11 metastases using the simultaneous integrated boost technique to deliver 35 to 40 and 20 to 25 Gy for high dose and elective dose planning target volume (PTVHD and PTVED), respectively. The HA plans were retrospectively generated using 1 coplanar and 2 noncoplanar arcs. Subsequently, the doses to the targets and OARs were compared. The HA plans provided significantly higher (p < 0.05) Dmin (77.4 ± 13.1%), D99% (89.3 ± 8.9%), and D98% (92.5 ± 7.7%) for gross tumor volume (GTV) than those of the VMAT plans (73.4 ± 12.2%, 84.2 ± 9.6 and 87.3 ± 8.8% for Dmin, D99% and D98%, respectively). In addition, D99% and D98% for PTVHD were significantly higher in the HA plans, whereas dosimetric parameters were comparable between the HA and VMAT plans for PTVED. The Dmax values for the brachial plexus, esophagus, and spinal cord were comparable, and no significant difference was observed in the Dmean for the larynx, pharyngeal constrictor, thyroid, parotid grand (left and right), and Submandibular gland (left and right). The HA plans provided significantly higher target coverage of GTV and PTVHD, with a comparable dose for OARs with VMAT plans. The results of this study may contribute to the improvement of local control in clinical practice.

Comparison of dosimetric parameters and robustness for rotational errors in fractionated stereotactic irradiation using automated noncoplanar volumetric modulated arc therapy for patients with brain metastases: single- versus multi-isocentric technique.

To compare the dosimetric parameters of automated noncoplanar volumetric modulated arc therapy plans using single-isocentric (SIC) and multi-isocentric (MIC) techniques for patients with two brain metastases (BMs) in stereotactic irradiation and to evaluate the robustness of rotational errors. The SIC and MIC plans were retrospectively generated (35 Gy/five fractions) for 58 patients. Subsequently, a receiver operating characteristic curve analysis between the tumor surface distance (TSD) and V25Gy was performed to determine the thresholds for the brain tissue. The SIC and MIC plans were recalculated based on the rotational images to evaluate the dosimetric impact of rotational error. The MIC plans showed better brain tissue sparing for TSD > 6.6 cm. The SIC plans provided a significantly better conformity index for TSD ≤ 6.6 cm, while significantly lower gradient index was obtained (3.22 ± 0.56vs. 3.30 ± 0.57, p < 0.05) in the MIC plans with TSD > 6.6 cm. For organs at risk (OARs) (brainstem, chiasm, lens, optic nerves, and retinas), D0.1 cc was significantly lower (p < 0.05) in the MIC plans than in the SIC plans. The prescription dose could be delivered (D99%) to the gross tumor volume (GTV) for patients with TSD ≤ 6.6 cm when the rotational error was < 1°, whereas 31% of the D99% of GTV fell below the prescription dose with TSD > 6.6 cm. MIC plans can be an optimal approach for reducing doses to OARs and providing robustness against rotational errors in BMs with TSD > 6.6 cm.

Definitive radiotherapy consisting of external beam radiotherapy without central shielding and 3D image-guided brachytherapy for patients with cervical cancer: feasibility for Japanese patients and dose-response analyses for local control in the low-dose range.

OBJECTIVE: To assess the feasibility of external beam radiotherapy without central shielding in definitive radiotherapy for Japanese patients with cervical cancer. METHODS: We retrospectively analysed the data of cervical cancer patients treated with definitive radiotherapy consisting of external beam radiotherapy without central shielding and three-dimensional-image-guided brachytherapy. RESULTS: The study included 167 patients (T1 + 2 = 108, T3 + 4 = 59) from eight Japanese institutions. For three-dimensional-image-guided brachytherapy, intra-cavitary and interstitial brachytherapy was utilized in 33 patients (20%). The median follow-up was 26.6 months (interquartile range, 20-43.2). The maximum rectal D2 (75 Gy)/bladder D2 (90 Gy) constraints were deviated by 6%/10% and 10%/5% for T1 + 2 and T3 + 4, respectively. The 2-year incidence of ≥grade 3 proctitis/cystitis was 4%/1% for T1 + 2 and 10%/2% for T3 + 4. The 2-year local progression-free survival was 89% for T1 + 2 and 82% for T3 + 4. For T1 + 2, the 2-year local progression-free survival for the high-risk clinical target volume D90 ≥ 68 Gy (indicated by receiver operating characteristic analysis; area under the curve = 0.711) was 92% versus 67% for <68 Gy (log-rank; P = 0.019). Cox multivariate analysis indicated that the high-risk clinical target volume D90 was one of independent predictors of local failure (P = 0.0006). For T3 + 4, the 2-year local progression-free survival was 87% for the high-risk clinical target volume <82 cm3 (area under the curve = 0.67) and 43% for ≥82 cm3 (P = 0.0004). Only the high-risk clinical target volume was an independent predictor of local failure (P = 0.0024). CONCLUSIONS: Definitive radiotherapy consisting of external beam radiotherapy without central shielding and three-dimensional-image-guided brachytherapy was feasible for Japanese patients with cervical cancer. Dose de-escalation from the current global standards is suggested for patients with T1 + 2 disease.

A phase II randomized trial of metastasis-directed therapy with alpha emitter radium-223 in men with oligometastatic castration-resistant prostate cancer (MEDAL).

BACKGROUND: The significance of metastasis-directed therapy for oligometastatic prostate cancer has been widely discussed, and targeted therapy for progressive sites is a feasible option as a multidisciplinary treatment for castration-resistant prostate cancer (CRPC). When oligometastatic CRPC with only bone metastases progresses after targeted therapy, it tends to progress as multiple bone metastases. The progression of oligometastatic CRPC after targeted therapy may be due in part to the presence of micrometastatic lesions that, though undetected on imaging, were present prior to targeted therapy. Thus the systemic treatment of micrometastases in combination with targeted therapy for progressive sites is expected to enhance the therapeutic effect. Radium-223 dichloride (radium-223) is a radiopharmaceutical that selectively binds to sites of increased bone turnover and inhibits the growth of adjacent tumor cells by emitting alpha rays. Therefore, for oligometastatic CRPC with only bone metastases, radium-223 may enhance the therapeutic effect of radiotherapy for active metastases. METHODS: This phase II, randomized trial of Metastasis-Directed therapy with ALpha emitter radium-223 in men with oligometastatic CRPC (MEDAL) is designed to assess the utility of radium-223 in combination with metastasis-directed radiotherapy in patients with oligometastatic CRPC confined to bone. In this trial, patients with oligometastatic CRPC with three or fewer bone metastases on whole-body MRI with diffusion-weighted MRI (WB-DWI) will be randomized in a 1:1 ratio to receive radiotherapy for active metastases plus radium-223 or radiotherapy for active metastases alone. The prior use of androgen receptor axis-targeted therapy and prostate-specific antigen doubling time will be used as allocation factors. The primary endpoint will be radiological progression-free survival against progression of bone metastases on WB-DWI. DISCUSSION: This will be the first randomized trial to evaluate the effect of radium-223 in combination with targeted therapy in oligometastatic CRPC patients. The combination of targeted therapy for macroscopic metastases with radiopharmaceuticals targeting micrometastasis is expected to be a promising new therapeutic strategy for patients with oligometastatic CRPC confined to bone. Trial registration Japan Registry of Clinical Trials (jRCT) (jRCTs031200358); Registered on March 1, 2021, https://jrct.niph.go.jp/latest-detail/jRCTs031200358.

Reirradiation for local recurrence of oral, pharyngeal, and laryngeal cancers: a multi-institutional study.

This study aimed to examine the efficacy and toxicity of reirradiation in patients with locally recurrent oral, pharyngeal, and laryngeal cancers. We conducted a retrospective, multi-institutional analysis of 129 patients with previously irradiated cancer. The most frequent primary sites were the nasopharynx (43.4%), oral cavity (24.8%), and oropharynx (18.6%). With a median follow-up duration of 10.6 months, the median overall survival was 14.4 months and the 2-year overall survival rate was 40.6%. For each primary site, the 2-year overall survival rates were 32.1%, 34.6%, 30%, 60.8%, and 5.7% for the hypopharynx, oral cavity, larynx, nasopharynx, and oropharynx, respectively. Prognostic factors for overall survival were primary site (nasopharynx versus other sites) and gross tumor volume (GTV) (≤ 25 cm3 versus > 25 cm3). The 2-year local control rate was 41.2%. Twenty-four patients (18.6%) presented with grade ≥ 3 toxicities, including nine with hemorrhages that led to grade 5 toxicities in seven patients. All nine tumors that caused hemorrhage showed tumor encasement of the carotid ≥ 180 degrees and eight of nine tumors had larger GTV > 25 cm3. Reirradiation is a feasible treatment option for small local recurrence of oral, pharyngeal, and laryngeal cancers, with the requirement of a strict eligibility assessment for large tumors with carotid encasement.