Efficacy and safety of PLDR-IMRT for the re-irradiation of recurrent NPC: A prospective, single-arm, multicenter trial.

Salvage treatment of locoregionally recurrent nasopharyngeal carcinoma (NPC) requires weighing the benefits of re-irradiation against increased risks of toxicity. Here, we evaluated the outcomes of patients treated with intensity-modulated-based pulsed low-dose-rate radiotherapy (PLDR-IMRT) to enhance the curative effect of salvage treatment and reduce RT-related SAEs. A prospective clinical trial was conducted from March 2018 to March 2020 at multiple institutions. NPC patients who experienced relapse after radical therapy were re-irradiated with a median dose of 60 Gy (50.4-70 Gy)/30 f (28-35 f) using PLDR-IMRT. Thirty-six NPC patients who underwent PLDR-IMRT for locoregional recurrence were identified. With a median follow-up of 26.2 months, the objective response rate (ORR) of the entire cohort was 91.6%. The estimated mPFS duration was 28 months (95% CI: 24.9-31.1), and the estimated mLRFS duration was 30.4 months (95% CI: 25.2-35.5). The overall survival (OS) rate for all patients was 80.6%, the progression-free survival (PFS) rate was 75% and the cancer-specific survival (CSS) rate was 88.9% at 1 year. The LRFS and DMFS rates were 88.9% and 91.7%, respectively, at 1 year. A combination of systematic therapies could provide survival benefits to patients who experience NPC relapse (p < 0.05), and a Karnofsky performance status (KPS) score of ≥90 was a favorable factor for local control (p < 0.05). The incidence of acute SAEs (grade 3+) from PLDR was 22.2%, and the incidence of chronic SAEs was 19.4% among all patients. PLDR-IMRT combined with systematic therapy can effectively treat patients with locoregionally recurrent nasopharyngeal carcinoma and causes fewer adverse events than the rates expected with IMRT.

Optimization of a protocol for contrast-enhanced four-dimensional computed tomography imaging of thoracic tumors using minimal contrast agent.

PURPOSE: The accuracy of target delineation for node-positive thoracic tumors is dependent on both four-dimensional computed tomography (4D-CT) and contrast-enhanced three-dimensional (3D)-CT images; these scans enable the motion visualization of tumors and delineate the nodal areas. Combining the two techniques would be more effective; however, currently, there is no standard protocol for the contrast media injection parameters for contrast-enhanced 4D-CT (CE-4D-CT) scans because of its long scan durations and complexity. Thus, we aimed to perform quantitative and qualitative assessments of the image quality of single contrast-enhanced 4D-CT scans to simplify this process and improve the accuracy of target delineation in order to replace the standard clinical modality involved in administering radiotherapy for thoracic tumors. METHODS: Ninety consecutive patients with thoracic tumors were randomly and parallelly assigned to one of nine subgroups subjected to CE-4D-CT scans with the administration of contrast agent volume equal to the patient's weight but different flow rate and scan delay time (protocol A1: flow rate of 2.0 ml/s, delay time of 15 s; A2: 2.0 ml/s, 20 s; A3: 2.0 ml/s, 25 s; B1: 2.5 ml/s, 15 s; B2: 2.5 ml/s, 20 s; B3: 2.5 ml/s, 25 s; C1: 3.0 ml/s, 15 s; C2: 3.0 ml/s, 20 s; C3: 3.0 ml/s, 25 s). The Hounsfield unit (HU) values of the thoracic aorta, pulmonary artery stem, pulmonary veins, carotid artery, and jugular vein were acquired for each protocol. Both quantitative and qualitative image analysis and delineation acceptability were assessed. RESULTS: The results revealed significant differences among the nine protocols. Enhancement of the vascular structures in mediastinal and perihilar regions was more effective with protocol A1 or A2; however, when interested in the region of superior mediastinum and supraclavicular fossa, protocol C2 or C3 is recommended. CONCLUSION: Qualitatively acceptable enhancement on contrast-enhanced 4D-CT images of thoracic tumors can be obtained by varying the flow rate and delay time when minimal contrast agent is used.

Evaluating the positional uncertainty of intrafraction, adjacent fields, and daily setup with the BrainLAB ExacTrac system in patients who are receiving craniospinal irradiation.

PURPOSE: To investigate the daily setup, interfraction motion, variability in the junction areas, and dosimetric effect in craniospinal irradiation (CSI) patients. METHODS: Fifteen CSI patients who had undergone split-field IMRT were followed in the study. Previous, middle, and posttreatment, each target volume position was evaluated using the ExacTrac system. Interfraction and intrafraction motions, the margin of the junction in adjacent targets volumes, and the dosimetric effect of the longitudinal residual error were analyzed. RESULTS: The lowest attainment rate within the tolerance of the initial setup error was 66.79% in six directions. The values of the initial error were within 15 mm (SD 4.5 mm) in the translation direction and 5° (SD 1.3°) in the rotation direction after the transposition of the treatment isocenter. With the guidance of the ExacTrac system, the interfraction and intrafraction residual errors were almost within the tolerance after correction, the margin of CTV-to-PCTV was in the range of target expansion criteria. The residual longitudinal errors resulted in only slight changes in the mean doses of PGTV and PCTV, while the maximum dose of the spinal cord increased by 16.1%. The patients did not exhibit any side-effects by the overall treatment during the follow-up period. CONCLUSIONS: Position correction is necessary after setup and the transposition of the treatment isocenter. Intra-fraction motion in the lateral direction should be monitored throughout treatment. The position errors in junction areas are almost within the tolerance after correction. The patients did not exhibit any side-effects by the overall treatment.

Pulsed reduced dose-rate radiotherapy as re-irradiation for brain metastasis in a patient with lung squamous-celled carcinoma.

The recurrence and progression of brain metastases after brain irradiation are a major cause of mortality and morbidity in patients with cancer. The risk of radiation-induced neurotoxicity and efficacy probably leads oncologists to not consider re-irradiation. We report the case of a 48-year-old Asian male diagnosed with squamous cell lung cancer and multiple brain metastases initially treated with 40 Gy whole-brain radiotherapy and 20 Gy partial brain boost. Fourteen gray stereotactic radiosurgery as salvage for brain metastases in the left occipital lobe was performed after initial irradiation. The recurrence of brain metastases in the left occipital lobe was demonstrated on magnetic resonance imaging at 9 months after initial radiotherapy. He received the second course of 28 Gy stereotactic radiosurgery for the recurrent brain metastases in the left occipital lobe. The third relapse of brain metastases was demonstrated by a magnetic resonance imaging scan at 7 months after the second radiotherapy. The third course of irradiation was performed because he refused to undergo surgical resection of the recurrent brain metastases. The third course of irradiation used a pulsed reduced dose-rate radiotherapy technique. It was delivered in a series of 0.2 Gy pulses separated by 3-min intervals. The recurrent brain metastases were treated with a dose of 60 Gy using 30 daily fractions of 2 Gy. Despite the brain metastases receiving 162 Gy irradiation, this patient had no apparent acute or late neurologic toxicities and showed clinical improvement. This is the first report of the pulsed reduced dose-rate radiotherapy technique being used as the third course of radiotherapy for recurrent brain metastases.

The clinical feasibility and performance of an orthogonal X-ray imaging system for image-guided radiotherapy in nasopharyngeal cancer patients: Comparison with cone-beam CT.

The demand for greater accuracy of intensity-modulated radiotherapy (IMRT) has driven the development of more advanced verification systems for image-guided radiotherapy (IGRT). The purpose of this study is to investigate setup discrepancies measured between an orthogonal X-ray guidance system (XGS-10) and cone-beam computed tomography (CBCT) of Varian in the IMRT of patients with nasopharyngeal cancer (NPC). The setup errors measured by XGS-10 and CBCT at the treatment unit with respect to the planning CTs were recorded for 30 patients with NPC. The differences in residual setup errors between XGS-10 system and CBCT were computed and quantitatively analyzed. The time of image acquisition and image registration was recorded. The radiation doses delivered by CBCT and XGS-10 were measured using PTW0.6CC ionization chambers and a water phantom. The differences between setup errors measured by the XGS-10 system and CBCT were generally <1.5 mm for translations, indicating a reasonably good agreement between the two systems for patients with NPC in the translation directions of A-P (P = 0.856), L-R (P = 0.856) and S-I (P = 0.765). Moreover, compared with CBCT, XGS-10 took much shorter image acquisition and registration time (P <0.001) and delivered only a small fraction of extra radiation dose to the patients (P <0.001). These results indicate that XGS-10 offers high localization accuracy similar to CBCT and additional benefits including prompt imaging process, low imaging radiation exposure, real time monitoring, which therefore represents a potential attractive alternative to CBCT for clinical use.

Use of cetuximab in combination with pulsed reduced dose-rate radiotherapy in a patient with recurrence of nasopharyngeal carcinoma in the neck.

Reirradiation is a major therapeutic modality for patients with locally recurrent head and neck carcinoma. Due to normal tissue tolerances, reirradiation using conventional techniques has a narrow therapeutic ratio in the regional recurrence of nasopharyngeal carcinoma (NPC). Pulsed reduced dose-rate radiotherapy (PRDR), which delivers a series of 0.2 Gy pulses separated by 3 min intervals, is a new reirradiation technique. Head and neck carcinoma cells have high levels of epidermal growth factor receptor expression and cetuximab shows a clear benefit to locally advanced head and neck carcinoma. We report a 56-year-old male with a recurrent lesion of NPC in the neck following initial radical radiochemotherapy. The patient was retreated with PRDR and concurrent cetuximab. The total dose of PRDR was 70 Gy, using 35 daily fractions of 2.0 Gy. The recurrent lesion of this patient had a complete response with no apparent radiation-induced normal tissue complications. This is the first study concerning PRDR combined with cetuximab for the treatment of recurrent head and neck carcinoma following radiotherapy. The outcome of this patient reveals that treatment with PRDR and concurrent cetuximab is a promising therapeutic option for patients with recurrent head and neck carcinoma following radiotherapy.