A novel evaluation model of image registration for cone-beam computed tomography guided lung cancer radiotherapy.

BACKGROUND: The aim of the study was to establish a weighted comprehensive evaluation model (WCEM) of image registration for cone-beam computed tomography (CBCT) guided lung cancer radiotherapy that considers the geometric accuracy of gross target volume (GTV) and organs at risk (OARs), and assess the registration accuracy of different image registration methods to provide clinical references. METHODS: The planning CT and CBCT images of 20 lung cancer patients were registered using diverse algorithms (bony and grayscale) and regions of interest (target, ipsilateral, and body). We compared the coverage ratio (CR) of the planning target volume (PTVCT) to GTVCBCT, as well as the dice similarity coefficient (DSC) of the GTV and OARs, considering the treatment position across various registration methods. Furthermore, we developed a mathematical model to assess registration results comprehensively. This model was evaluated and validated using CRFs across four automatic registration methods. RESULTS: The grayscale registration method, coupled with the registration of the ipsilateral structure, exhibited the highest level of automatic registration accuracy, the DSC were 0.87 ± 0.09 (GTV), 0.71 ± 0.09 (esophagus), 0.74 ± 0.09 (spinal cord), and 0.91 ± 0.05 (heart), respectively. Our proposed WCEM proved to be both practical and effective. The results clearly indicated that the grayscale registration method, when applied to the ipsilateral structure, achieved the highest CRF score. The average CRF scores, excellent rates, good rate and qualification rates were 58 ± 26, 40%, 75%, and 85%, respectively. CONCLUSIONS: This study successfully developed a clinically relevant weighted evaluation model for CBCT-guided lung cancer radiotherapy. Validation confirmed the grayscale method's optimal performance in ipsilateral structure registration.

Commissioning and clinical evaluation of a novel high-resolution quality assurance digital detector array for SRS and SBRT.

PURPOSE: We aimed to perform the commissioning and clinical evaluation of myQA SRS detector array for patient-specific quality assurance (PSQA) of stereotactic radiosurgery (SRS)/ stereotactic body radiotherapy (SBRT) plans. METHODS: To perform the commissioning of myQA SRS, its dose linearity, dose-rate dependence, angular dependence, and field-size dependence were investigated. Ten SBRT plans were selected for clinical evaluation: 1) Common clinical deviations based on the original SBRT plan (Plan0), including multileaf collimator (MLC) positioning deviation and treatment positioning deviation were introduced. 2) Compared the performance of the myQA SRS and a high-resolution EPID dosimetry system in PSQA measurement for the SBRT plans. Evaluation parameters include gamma passing rate (GPR) and distance-to-agreement (DTA) pass rate (DPR). RESULTS: The dose linearity, angle dependence, and field-size dependence of myQA SRS system exhibit excellent performance. The myQA SRS is highly sensitive in the detection of MLC deviations. The GPR of (3%/1 mm) decreases from 90.4% of the original plan to 72.7%/62.9% with an MLC outward/inward deviation of 3 mm. Additionally, when the setup error deviates by 1 mm in the X, Y, and Z directions with the GPR of (3%/1 mm) decreasing by an average of -20.9%, -25.7%, and -24.7%, respectively, and DPR (1 mm) decreasing by an average of -33.7%, -32.9%, and -29.8%. Additionally, the myQA SRS has a slightly higher GPR than EPID for PSQA, However, the difference is not statistically significant with the GPR of (3%/1 mm) of (average 90.4%% vs. 90.1%, p = 0.414). CONCLUSION: Dosimetry characteristics of the myQA SRS device meets the accuracy and sensitivity requirement of PSQA for SRS/SBRT treatment. The dose rate dependence should be adequately calibrated before its application and a more stringent GPR (3%/1 mm) evaluation criterion is suggested when it is used for SRS/SBRT QA.

Concurrent Chemoradiation Therapy With or Without Nimotuzumab in Locally Advanced Squamous Cell Lung Cancer: A Phase 2 Randomized Trial.

PURPOSE: The study aimed to evaluate the efficacy and safety of concurrent chemoradiation therapy (CCRT) combined with nimotuzumab in patients with unresectable stage III squamous cell lung cancer (SqCLC). METHODS AND MATERIALS: A prospective, single-center, open-label, randomized phase 2 trial was performed in patients with unresectable stage III SqCLC. Patients were randomized to receive 65 Gy thoracic radiation over 5 weeks concurrent with docetaxel and cisplatin or the same CCRT regimen combined with 200 mg of nimotuzumab (NIMO-CCRT), administered weekly by intravenous infusion. The primary endpoint was overall survival. The secondary endpoints were progression-free survival, objective response rate, failure patterns, and treatment-related toxicity. RESULTS: From August 2015 to June 2020, 126 patients with SqCLC were randomized. Four patients withdrew consent before the start of treatment, and 122 patients were included for analysis, including 57 in the NIMO-CCRT group and 65 in the CCRT group. The median OS was 24.9 months in the NIMO-CCRT group and 23.5 months in the CCRT group (P = .655). The median PFS was 12.1 months in the NIMO-CCRT group and 13.7 months in the CCRT group (P = .968). The NIMO-CCRT group had a significantly lower risk of brain metastasis, with adjusted subdistribution hazard ratio of 0.099 (95% confidence interval, 0.012-0.81; P = .031). The incidence of grade ≥3 pneumonitis (P = .894) and esophagitis (P = .974) was similar between the 2 arms. There was no grade 2 or higher skin toxicity in NIMO-CCRT group. CONCLUSIONS: The coincident application of nimotuzumab with CCRT was well tolerated for locally advanced SCCL. The NIMO-CCRT group had an OS and PFS similar to that in the CCRT group, but a lower risk of brain metastasis. Further investigations are warranted.

Hypo-fractionated radiotherapy with concurrent chemotherapy for locoregional recurrence of non-small cell lung cancer after complete resection: A prospective, single-arm, phase II study (GASTO-1017).

OBJECTIVES: To explore the efficacy and toxicities of split-course hypo-fractionated radiotherapy with concurrent chemotherapy (HFRT-CHT) with intensity modulated radiotherapy (IMRT) technique in non-small cell lung cancer (NSCLC) patients with postoperative locoregional recurrence (LRR). MATERIALS AND METHODS: NSCLC patients were eligible if confirmed as LRR disease without distant metastasis after complete resection. HFRT-CHT using IMRT technique was administered with 51 Gy in 17 fractions or 40 Gy in 10 fractions as the first course followed by a break. Patients with no disease progression and no persistent Grade ≥2 toxicities had the second course of 15 Gy in 5 fractions or 28 Gy in 7 fractions as a boost. The primary endpoint was progression-free survival (PFS). RESULTS: Fifty-eight patients were enrolled and analyzed. With a median follow-up of 23.9 months for all, the 2-year and 3-year PFS rate was 59.7 % and 46.4 %, the 2-year and 3-year OS rate was 72.5 % and 52.2 %, respectively, and a favorable objective response rate of 95.9 % was obtained after the whole courses protocol. Grade 3 acute pneumonitis and esophagitis occurred in 2 (3.4 %) and 7 (12.1 %) patients, and fatal pneumonitis was reported in one case (1.7 %). Exploratory subgroup analysis showed that performance status (PS) (PS 0 vs. 1: 2-year PFS, 88.1 % vs. 46.9 %,P = 0.001; 2-year OS, 100 % vs. 59.4 %, P < 0.001), recurrence site (single vs. multiple: 2-year PFS, 93.8 % vs. 47.4 %, P = 0.008; 2-year OS, 100 % vs. 63.0 %, P = 0.001), and gross tumor volume (GTV) (<50cm3 vs. ≥ 50cm3: 2-year PFS, 70.6 % vs. 46.2 %, P = 0.024; 2-year OS, 85.6 % vs. 57.4 %, P = 0.034) were significantly associated with PFS and OS. CONCLUSION: Split-course HFRT-CHT with IMRT technique achieved promising disease control and satisfactory survival with moderate toxicities in postoperative LRR of NSCLC. Good PS, a single recurrence site and GTV<50cm3 tended to have prolonged PFS and OS. Early detection of LRR may improve the efficacy of HFRT-CHT.

Moderately Hypofractionated Once-Daily Compared With Twice-Daily Thoracic Radiation Therapy Concurrently With Etoposide and Cisplatin in Limited-Stage Small Cell Lung Cancer: A Multicenter, Phase II, Randomized Trial.

PURPOSE: Chemotherapy and concurrent thoracic radiation therapy (CCTRT) followed by prophylactic cranial irradiation (PCI) is the standard of care for limited-stage small cell lung cancer (LS-SCLC). We aimed to compare the efficacy and toxicity of moderately hypofractionated once-daily CCTRT with that of a standard twice-daily regimen. METHODS AND MATERIALS: This multicenter, phase 2, randomized study enrolled patients aged 18 to 75 years old who had pathologically confirmed LS-SCLC and an Eastern Cooperative Oncology Group performance status of 0 to 1. Eligible patients received 4 to 6 cycles of etoposide-cisplatin chemotherapy and were randomized to receive twice-daily CCTRT at 45 Gray (Gy) in 30 fractions or once-daily CCTRT at 65 Gy in 26 fractions, commencing with cycles 1 to 3 of chemotherapy. PCI was given to good responders. The primary endpoint was progression-free survival (PFS). RESULTS: The analyses included 182 patients, with 94 in the twice-daily group and 88 in the once-daily group. CCTRT started with cycle 3 of chemotherapy for most patients (80.2%). At a median follow-up of 24.3 months, the median PFS was 13.4 months (95% confidence interval [CI], 10.8-16.0) in the twice-daily group versus 17.2 months (95% CI, 11.8-22.6) in the once-daily group (P = .031), with 2-year PFS rates of 28.4% (95% CI, 18.2-38.6) and 42.3% (95% CI, 31.1-53.5), respectively. The estimated overall survival was 33.6 months in the twice-daily group versus 39.3 months in the once-daily group (P = .137). The median locoregional PFS was 23.9 months in the twice-daily group and was not reached in the once-daily group (P = .017). The incidences of most toxicities were similar in both groups, except for a higher incidence of ≥grade 3 acute lymphopenia in the once-daily group (71.7% vs 40.2% in the twice-daily group; P < .001). There was no difference in the incidences of ≥grade 3 esophagitis (17.4% vs 15.3%, respectively), pneumonitis (3.3% vs 2.4%, respectively) or treatment-related death (2.2% vs 1.2%, respectively) between the once-daily and twice-daily groups. CONCLUSIONS: Moderately hypofractionated, once-daily CCTRT showed improved PFS and similar toxicities compared with twice-daily CCTRT in LS-SCLC. This regimen should be evaluated for comparison in a phase 3 randomized trial.

Comparison of set up accuracy among three common immobilisation systems for intensity modulated radiotherapy of nasopharyngeal carcinoma patients.

INTRODUCTION: In intensity modulated radiotherapy (IMRT) of nasopharyngeal carcinoma (NPC) patients, an effective immobilisation system is important to minimise set up deviation. This study evaluated the effectiveness of three immobilisation systems by assessing their set up deviations. METHODS: Patients were randomly assigned to one of the three immobilisation systems: (1) supine on head rest and base plate (HB); (2) supine with alpha cradle supporting the head and shoulder (AC); (3) supine with vacuum bag supporting the head and shoulder (VB). CBCT was conducted weekly for each patient on the linear accelerator. Image registration was conducted at the nasopharynx (NP) and cervical regions. The translational displacements (latero-medial, antero-posterior and cranio-caudal), rotational displacements (pitch, yaw and roll) and 3D vectors obtained at the NP and cervical regions were recorded and compared among the three systems. RESULTS: The mean translational and rotational deviations were within 3 mm and 2°, respectively, and the range of 3D vector was 1.53-3.47 mm. At the NP region, the AC system demonstrated the smallest translational and rotational deviations and 3D vector. The differences were significant except for the latero-medial, yaw and roll directions. Similarly, at the cervical region, the AC system showed smaller translational and rotational deviations and 3D vector, with only the cranio-caudal and yaw deviations that did not reach statistical significance. CONCLUSIONS: Set up deviation was greater in the neck than the NP region. The set up accuracy of the AC system was better than the other two systems, and it is recommended for IMRT of NPC patients in our institution.

Dosimetric benefit to organs at risk following margin reductions in nasopharyngeal carcinoma treated with intensity-modulated radiation therapy.

INTRODUCTION: It is important to decrease the radiation exposure of normal tissue in intensity-modulated radiation therapy (IMRT). Minimizing planning target volume (PTV) margins with more precise target localization techniques can achieve this goal. This study aimed to quantify the extent to which organs at risk (OARs) are spared when using reduced margins in the treatment of nasopharyngeal carcinoma (NPC). METHODS: Two IMRT plans were regenerated for 40 patients with NPC based on two PTV margins, which were reduced or unchanged following cone beam computed tomography online correction. The reduced-margin plan was optimized based on maximal dose reduction to OARs without compromising target coverage. Dosimetric comparisons were evaluated in terms of target coverage and OAR sparing. RESULTS: Improvements in target coverage occurred with margin reduction, and significant improvements in dosimetric parameters were observed for all OARs (P < 0.05) except for the right optic nerve, chiasm, and lens. Doses to OARs decreased at a rate of 1.5% to 7.7%. Sparing of the left parotid and right parotid, where the mean dose (Dmean) decreased at a rate of 7.1% and 7.7%, respectively, was greater than the sparing of other OARs. CONCLUSIONS: Significant improvements in OAR sparing were observed with margin reduction, in addition to improvement in target coverage. The parotids benefited most from the online imaging-guided approach.

Evaluation of inter-fraction and intra-fraction errors during volumetric modulated arc therapy in nasopharyngeal carcinoma patients.

BACKGROUND: This prospective study was conducted to evaluate inter- and intra-fraction errors in nasopharyngeal carcinoma (NPC) patients undergoing volumetric modulated arc therapy (VMAT) using cone-beam computed tomography (CBCT) and to thus obtain planning target volume (PTV) margins to effectively guide treatment in the future. METHODS: Fifteen NPC patients scheduled to undergo VMAT were prospectively enrolled in the study. For each patient, three CBCT scans were obtained; one after daily conventional positioning, one after online correction with 2 mm tolerance and one after 1 week of VMAT delivery. The scans were registered to the planning CT to determine the inter- and intra-fraction errors. Patient positioning errors were analyzed for time trends over the course of radiotherapy. PTV margins were calculated from the systematic (Σ) and random (σ) errors. RESULTS: The average absolute values of the pre-correction, post-correction and intra-fraction errors (in order) were 1.1, 0.6 and 0.4 mm in the medial-lateral (ML) direction, 1.2, 0.7 and 0.5 mm in the superior-inferior (SI) direction and 1.1, 0.7 and 0.5 mm in the anterior-posterior (AP) direction. The corresponding Σ were 1.0-1.4 mm, 0.4-0.5 mm and 0.2-0.4 mm, while the corresponding σ were 0.7-0.8 mm, 0.6-0.7 mm and 0.5-0.6 mm. With time, gradual increases in both the inter- and intra-fraction three-dimensional displacements were observed (P = 0.019 and P = 0.044, respectively). The total PTV margins accounting for pre-correction and intra-fraction errors were 3.4-4.1 mm and those accounting for post-correction and intra-fraction errors were 1.7-2.2 mm. CONCLUSIONS: CBCT is an effective modality to evaluate and improve the accuracy of VMAT in NPC patients. Inter- and intra-fraction three-dimensional displacements increased as a function of time during the course of radiotherapy. In our institution, we recommend a PTV margin of 5 mm for NPC patients undergoing VMAT without CBCT and 3 mm for those treated with rigorous daily CBCT scans.