And Yet It Moves: Clinical Outcomes and Motion Management in Stereotactic Body Radiation Therapy (SBRT) of Centrally Located Non-Small Cell Lung Cancer (NSCLC): Shedding Light on the Internal Organ at Risk Volume (IRV) Concept

Abstract

The internal organ at risk volume (IRV) concept might improve toxicity profiles in stereotactic body radiation therapy (SBRT) for non-small cell lung cancer (NSCLC). We studied (1) clinical aspects in central vs. peripheral tumors, (2) the IRV concept in central tumors, (3) organ motion, and (4) associated normal tissue complication probabilities (NTCPs). We analyzed patients who received SBRT for NSCLC (clinical aspects, n = 78; motion management, n = 35). We found lower biologically effective doses, larger planning target volume sizes, higher lung doses, and worse locoregional control for central vs. peripheral tumors. Organ motion was greater in males and tall patients (bronchial tree), whereas volume changes were lower in patients with a high body mass index (BMI) (esophagus). Applying the IRV concept (retrospectively, without new optimization), we found an absolute increase of >10% in NTCPs for the bronchial tree in three patients. This study emphasizes the need to optimize methods to balance dose escalation with toxicities in central tumors. There is evidence that organ motion/volume changes could be more pronounced in males and tall patients, and less pronounced in patients with higher BMI. Since recent studies have made efforts to further subclassify central tumors to refine treatment, the IRV concept should be considered for optimal risk assessment.

Keywords: IRV; NSCLC; PRV; SBRT; central tumors; clinical characteristics; clinical outcomes; internal organ at risk volume; motion management; planning organ at risk volume.

Figure 1

The flow chart illustrates the patient selection for the comparison of clinical characteristics in centrally vs. peripherally located tumors (left side, blue background) and the studies on motion management for OARs (right side, orange background). SBRT: stereotactic body radiation therapy. OARs: organs at risk. IRV: internal organ at risk volume.

Figure 2

Comparison of locoregional control (LRC) in patients with centrally vs. peripherally located tumors (distance to organs at risk: central airways, spinal canal, esophagus, ≤2 cm vs. >2 cm). The 2-year LRC was 94.4% vs. 64.8%.

Figure 3

Comparison of locoregional progression-free survival (LPFS) in patients with tumors at a distance ≤2 cm vs. >2 cm from the central airways. The 2-year LPFS was 62.4% vs. 33.8%.

Figure 4

(a) Influence of gender on the maximum vector of movement for the bronchial tree (length, mm). Male patients had greater movement (median 5.7 mm vs. 3.9 mm, p < 0.05, 21 male patients vs. 14 female patients). (b) Influence of body height on the maximum vector of movement for the bronchial tree (length, mm). Tall patients had greater movement (median 5.7 mm vs. 3.6 mm, p < 0.05; cut-off median of body height [1.68 m], 16 patients with smaller height vs. 19 patients with height ≥ median). * Values that are more than 3x interquartile range below first quartile or above third quartile. (c) Influence of the body mass index (BMI) on the volume changes of the esophagus. Here, we compared organs at risk and corresponding internal organs at risk volumes. Patients with high BMI had lower volume changes (median 56.7% vs. 40.5%, p < 0.05, cut-off 25 kg/m², 13 patients with BMI ≤ 25 kg/m² vs. 22 patients with higher BMI).

Figure 4

(a) Influence of gender on the maximum vector of movement for the bronchial tree (length, mm). Male patients had greater movement (median 5.7 mm vs. 3.9 mm, p < 0.05, 21 male patients vs. 14 female patients). (b) Influence of body height on the maximum vector of movement for the bronchial tree (length, mm). Tall patients had greater movement (median 5.7 mm vs. 3.6 mm, p < 0.05; cut-off median of body height [1.68 m], 16 patients with smaller height vs. 19 patients with height ≥ median). * Values that are more than 3x interquartile range below first quartile or above third quartile. (c) Influence of the body mass index (BMI) on the volume changes of the esophagus. Here, we compared organs at risk and corresponding internal organs at risk volumes. Patients with high BMI had lower volume changes (median 56.7% vs. 40.5%, p < 0.05, cut-off 25 kg/m², 13 patients with BMI ≤ 25 kg/m² vs. 22 patients with higher BMI).

Figure 5

Illustration of the respiration-dependent movement of the bronchial tree. Patient with a stage IIA adenocarcinoma of the right upper lobe. SBRT was applied up to 60 Gy in 8 fractions prescribed on the 80% isodose using VMAT. The images depict the corresponding slices of the 4D-CT scan with maximum inhalation (A) and maximum exhalation (B). In (C) (average intensity projection CT scan), the dose is shown from 60 Gy (blue) to 75 Gy (red) with the contours of the bronchial tree in turquoise (* maximum inhalation, ** maximum exhalation). In the image (D) and magnification of image (C), the gain in volume between internal organ at risk volume (IRV) and organ at risk (OAR) is marked (***). The distance between the GTV and the bronchial tree was 3 mm. Please note the relevant volume difference between OAR and IRV in proximity to the target volume. The absolute difference in volume between the bronchial tree (59.0 cm³) and its corresponding IRV (94.4 cm³) was 35.5 cm³ (relative increase in volume, 60%). The maximum difference in geometric centers between OAR and IRV was 10.1 mm. The absolute difference in maximum dose was 8.4 Gy (OAR, 62.9 Gy vs. IRV, 71.2 Gy). The absolute increase in normal tissue complication probability, when comparing OAR vs. IRV, was 11.5% (relative increase, 44.2%).