Purpose: Local failure rates after radiation therapy (RT) for locally advanced non–small-cell lung cancer (NSCLC) remain high. Consequently, RT dose intensification strategies continue to be explored, including hypofractionation, which allows for RT acceleration that could potentially improve outcomes. The maximum-tolerated dose (MTD) with dose-escalated hypofractionation has not been adequately defined. Patients and Methods: Seventy-nine patients with NSCLC were enrolled on a prospective single-institution phase I trial of dose-escalated hypofractionated RT without concurrent chemotherapy. Escalation of dose per fraction was performed according to patients' stratified risk for radiation pneumonitis with total RT doses ranging from 57 to 85.5 Gy in 25 daily fractions over 5 weeks using intensity-modulated radiotherapy. The MTD was defined as the maximum dose with ≤ 20% risk of severe toxicity. Results: No grade 3 pneumonitis was observed and an MTD for acute toxicity was not identified during patient accrual. However, with a longer follow-up period, grade 4 to 5 toxicity occurred in six patients and was correlated with total dose (P = .004). An MTD was identified at 63.25 Gy in 25 fractions. Late grade 4 to 5 toxicities were attributable to damage to central and perihilar structures and correlated with dose to the proximal bronchial tree. Conclusion: Although this dose-escalation model limited the rates of clinically significant pneumonitis, dose-limiting toxicity occurred and was dominated by late radiation toxicity involving central and perihilar structures. The identified dose-response for damage to the proximal bronchial tree warrants caution in future dose-intensification protocols, especially when using hypofractionation.

Cone-beam computed tomography (CBCT) has been clinically used to verify patient position and to localize the target of treatment in image-guided radiation therapy (IGRT). However, when the chest and the upper abdomen are scanned, respiratory-induced motion blurring limits the utility of CBCT. In order to mitigate this blurring, respiratory-gated CBCT, i.e. 4D CBCT, was introduced. In 4D CBCT, the cone-beam projection data sets acquired during a gantry rotation are sorted into several respiratory phases. In these gated reconstructions, the number of projections for each respiratory phase is significantly reduced. Consequently, undersampling streaking artifacts are present in the reconstructed images, and the image contrast resolution is also significantly compromised. In this paper, we present a new method to simultaneously achieve both high temporal resolution ( approximately 100 ms) and streaking artifact-free image volumes in 4D CBCT. The enabling technique is a newly proposed image reconstruction method, i.e. prior image constrained compressed sensing (PICCS), which enables accurate image reconstruction using vastly undersampled cone-beam projections and a fully sampled prior image. Using PICCS, a streak-free image can be reconstructed from 10-20 cone-beam projections while the signal-to-noise ratio is determined by a denoising feature of the selected objective function and by the prior image, which is reconstructed using all of the acquired cone-beam projections. This feature of PICCS breaks the connection between the temporal resolution and streaking artifacts' level in 4D CBCT. Numerical simulations and experimental phantom studies have been conducted to validate the method.

Use of helical TomoTherapy‐based MVCT imaging for adaptive planning is becoming increasingly popular. Treatment planning and dose calculations based on MVCT require an image value to electron density calibration to remain stable over the course of treatment time. In this work, we have studied the dosimetric impact on TomoTherapy treatment plans due to variation in image value to density table (IVDT) curve as a function of target degradation. We also have investigated the reproducibility and stability of the TomoTherapy MVCT image quality over time. Multiple scans of the TomoTherapy “Cheese” phantom were performed over a period of five months. Over this period, a difference of 4.7% in the HU values was observed in high‐density regions while there was no significant variation in the image values for the low densities of the IVDT curve. Changes in the IVDT curves before and after target replacement were measured. Two clinical treatment sites, pelvis and prostate, were selected to study the dosimetric impact of this variation. Dose was recalculated on the MVCTs with the planned fluence using IVDT curves acquired before and after target change. For the cases studied, target replacement resulted in an overall difference of less than 5%, which can be significant for hypo‐fractionated cases. Hence, it is recommended to measure the IVDT curves on a monthly basis and after any major repairs/replacements.PACS numbers: 87.55.Qr, 87.56.bd, 87.57.C, 87.57.Q

To compare stereotactic radiosurgery (SRS) plan quality metrics of manual forward planning (MFP) and Elekta Fast Inverse Planning™ (FIP)-based inversely optimized plans for patients treated with Gamma Knife®. Clinically treated, MFP SRS plans for 100 consecutive patients (115 lesions; 67 metastatic and 48 benign) were replanned with the FIP dose optimizer based on a convex linear programming formulation. Comparative plans were generated to match or exceed the following metrics in order of importance: Target Coverage (TC), Paddick Conformity Index (PCI), beam-on time (BOT), and Gradient Index (GI). Plan quality metrics and delivery parameters between MFP and FIP were compared for all lesions and stratified into subgroups for further analysis. Additionally, performance of FIP for multiple punctate (<4 mm) metastatic lesions on a subset of cases was investigated. A Wilcoxon signed-rank test for non-normal distributions was used to assess the statistical differences between the MFP and FIP treatment plans. Overall, 76% (87/115) of FIP plans showed a statistically significant improvement in plan quality compared to MFP plans. As compared to MFP, FIP plans demonstrated an increase in the median PCI by 1.1% (p<0.01), a decrease in GI by 3.7% (p< 0.01), and an increase in median number of shots by 74% (p< 0.01). TC and BOT were not statistically significantly different between MFP and FIP plans (p>0.05). FIP plans showed a statistically significant increase in use of 16 mm (p< 0.01) and blocked shots (p< 0.01), with a corresponding decrease in 4 mm shots (p< 0.01). Use of multiple shots per coordinate was significantly higher in FIP plans (p<0.01). The FIP optimizer failed to generate a clinically acceptable plan in 4/115 (3.5%) lesions despite optimization parameter changes. The mean optimization time for FIP plans was 5.0 min (Range: 1.0 - 10.0 min). In the setting of multiple punctate lesions, PCI for FIP was significantly improved (p<0.01) by changing the default low-dose/BOT penalty optimization setting from a default of 50/50 to 75-85/40. FIP offers a significant reduction in manual effort for SRS treatment planning while achieving comparable plan quality to an expert planner-substantially improving overall planning efficiency. FIP plans employ a non-intuitive increased use of blocked sectors and shot-in-shot technique to achieve high quality plans. Several FIP plans failed to achieve clinically acceptable treatments and warrant further investigation.