Intra- and inter-fractional variations of tumors with fiducial markers measured using respiratory-correlated computed tomography images for respiratory gated lung stereotactic body radiation therapy.

PURPOSE: This study evaluated the intra- and inter-fractional variation of tumors with fiducial markers (FMs), relative to the tumor-FM distance, to establish how close an FM should be inserted for respiratory-gated stereotactic body radiation therapy (RG-SBRT). METHODS: Forty-five lung tumors treated with RG-SBRT were enrolled. End-expiratory computed tomography (CT) (CTplan) and four-dimensional-CT (4D-CT) scans were obtained for planning. End-expiratory CT (CTfr) scanning was performed before each fraction. The FMs were divided into two groups based on the median tumor-FM distance in the CTplan (Dp). For the intra-fractional variation, the correlations between the corresponding tumor and FM intra-fractional motions, defined as the centroid coordinates of those in each 0-90% phase, with the 50% phase of 4D-CT as the origin, were calculated in the left-right, anterior-posterior, and superior-inferior directions. Furthermore, the maximum difference in the tumor-FM distance in each phase of 4D-CT scan, based on those in the 50% phase of 4D-CT scan (Dmax), was obtained. Inter-fractional variation was defined as the maximum distance between the tumors in CTplan and CTfr, when the CT scans were fused based on each FM or vertebra. RESULTS: The median Dp was 26.1 mm. While FM intra-fractional motions were significantly and strongly correlated with the tumor intra-fractional motions in only anterior-posterior and superior-inferior directions for the Dp > 26 mm group, they were significantly and strongly correlated in all directions for the Dp ≤ 26 mm group. In all directions, Dmax values of the Dp ≤ 26 mm group were lower than those of the Dp > 26 mm group. The inter-fractional variations based on the Dp ≤ 26 mm were smaller than those on the Dp > 26 mm and on the vertebra in all directions. CONCLUSIONS: Regarding intra- and inter-fractional variation, FMs for Dp ≤ 26 mm can increase the accuracy for RG-SBRT.

Deep inspiration breath hold real-time tumor-tracking radiation therapy (DBRT) as a novel stereotactic body radiation therapy approach for lung tumors.

Radiotherapy with deep inspiration breath hold (DIBH) reduces doses to the lungs and organs at risk. The stability of breath holding and reproducibility of tumor location are higher during expiration than during inspiration; therefore, we developed an irradiation method combining DIBH and real-time tumor-tracking radiotherapy (RTRT) (DBRT). Nine patients were enrolled in this study. Fiducial markers were placed near tumors using bronchoscopy. Treatment planning computed tomography (CT) was performed thrice during DIBH, assisted by spirometer-based device. Each CT scan was fused using fiducial markers. Gross tumor volume (GTV) was contoured for each dataset and summed to create GTVsum; adding a 5-mm margin around GTVsum generated the planning target volume. The prescribed dose was mainly 42 Gy in four fractions. The treatment plan was created using DIBH CT (DBRT-plan), with a similar treatment plan created for expiratory CT for cases for which DBRT could not be performed (conv-plan). Vx defined as the volume of the lung received x Gy, and the mean lung dose, V20, V10, and V5 were evaluated. DBRT was completed in all patients. Mean dose, V20, and V10 were significantly lower in the DBRT-plan than in the conv-plan (all p = 0.003). Mean rates of decrease for mean dose, V20, and V10 were 14.0%, 27.6%, and 19.1%, respectively. No significant difference was observed in V5. We developed DBRT, a stereotactic body radiation therapy performed with the DIBH technique; it combines a spirometer-based breath-hold support system with an RTRT system. All patients who underwent DBRT completed the procedure without any technical or mechanical complications. This is a promising methodology that may significantly reduce lung doses.

Immune Checkpoint Inhibitors after Radiation Therapy Improve Overall Survival Rates in Patients with Stage IV Lung Cancer.

This exploratory and retrospective study aimed to evaluate whether there is a difference in the overall survival (OS) rates of patients with stage IV lung cancer who underwent radiation therapy (RT) depending on the presence or absence of immune checkpoint inhibitors (ICIs) and the timing of their use. Eighty patients with histologically confirmed stage IV lung cancer were enrolled, and ICIs were administered to thirty (37.5%). ICIs were administered before RT and after RT in 11 and 20 patients, respectively. The median follow-up period was 6 (range: 1-37) months. Patients treated with ICIs had significantly better OS rates than those not treated with ICIs (p < 0.001). The 6-month OS rates in patients treated with and without ICIs were 76.3% and 34.5%, respectively. The group that received ICI therapy after RT had a significantly better OS rate than the group that received ICI therapy prior to RT (6-month OS: 94.7% vs. 40.0%, p < 0.001). In the multivariate analysis, performance status (0-1 vs. 2-4) and ICI use after RT were significant factors for OS (p = 0.032 and p < 0.001, respectively). Our results suggest that ICI administration after RT may prolong the OS of patients with stage IV lung cancer.

Differences in Radiosensitivity According to EGFR Mutation Status in Non-Small Cell Lung Cancer: A Clinical and In Vitro Study.

Unlike drug selection, radiation parameters (field, dose) are not based on driver gene mutations in patients with metastatic non-small cell lung cancer (NSCLC). This study aimed to compare radiosensitivity in NSCLC with and without EGFR driver gene mutations using clinical and in vitro data. The clinical study included 42 patients who underwent whole-brain radiotherapy for brain metastases from NSCLC; of these, 13 patients had EGFR mutation-positive tumors. The Kaplan-Meier method was used to calculate the cranial control rate without intracranial recurrence. In the in vitro study, colony formation and double-strand DNA breaks were examined in two EGFR mutation-negative and three EGFR mutation-positive NSCLC-derived cell lines. Colony formation was assessed 14 days after irradiation with 0 (control), 2, 4, or 8 Gy. DNA double-strand breaks were evaluated 0.5 and 24 h after irradiation. EGFR mutation-positive patients had a significantly better cranial control rates than EGFR mutation-negative patients (p = 0.021). EGFR mutation-positive cells formed significantly fewer colonies after irradiation with 2 or 4 Gy than EGFR mutation-negative cells (p = 0.002, respectively) and had significantly more DNA double-strand breaks at 24 h after irradiation (p < 0.001). Both clinical and in vitro data suggest that EGFR mutation-positive NSCLC is radiosensitive.

Fatigue Life Assessment of Welded Joints by Combined Measurements Using DIC and XRD.

The existing methods of assessing the fatigue life of welded joints fail to consider local strain ranges and mean stress at the weld toe. The present work proposes a novel approach to assessing the fatigue life of welded joints by conducting measurements with digital image correlation (DIC) and X-ray diffraction (XRD) in combination. Local strain ranges at the weld toe of gusset welded joints were measured by DIC. Hammer peening was conducted on the welded joints to introduce different initial stresses. The influence of mean stress was investigated by considering initial residual stress measured by XRD and a perfect plastic material model. The fatigue experiment was carried out on specimens with and without hammer peening. The results showed that hammer peening could offset adverse welding deformation effectively, and introduce significant residual compressive stress. The fatigue failure life increased by more than 15 times due to hammer peening. The fatigue initiation life assessed by the proposed method was close to that based on nominal stress, indicating that the proposed method is reliable for predicting the fatigue initiation life of welded joints.