Cone-Beam-CT Guided Adaptive Radiotherapy for Locally Advanced Non-small Cell Lung Cancer Enables Quality Assurance and Superior Sparing of Healthy Lung

Abstract

PurposeTo evaluate the potential of cone-beam-CT (CB-CT) guided adaptive radiotherapy (ART) for locally advanced non-small cell lung cancer (NSCLC) for sparing of surrounding organs-at-risk (OAR).Materials and MethodsIn 10 patients with locally advanced NSCLC, daily CB-CT imaging was acquired during radio- (n = 4) or radiochemotherapy (n = 6) for simulation of ART. Patients were treated with conventionally fractionated intensity-modulated radiotherapy (IMRT) with total doses of 60–66 Gy (pPlan) (311 fraction CB-CTs). OAR were segmented on every daily CB-CT and the tumor volumes were modified weekly depending on tumor changes. Doses actually delivered were recalculated on daily images (dPlan), and voxel-wise dose accumulation was performed using a deformable registration algorithm. For simulation of ART, treatment plans were adapted using the new contours and re-optimized weekly (aPlan).ResultsCB-CT showed continuous tumor regression of 1.1 ± 0.4% per day, leading to a residual gross tumor volume (GTV) of 65.3 ± 13.4% after 6 weeks of radiotherapy (p = 0.005). Corresponding PTVs decreased to 83.7 ± 7.8% (p = 0.005). In the actually delivered plans (dPlan), both conformity (p = 0.005) and homogeneity (p = 0.059) indices were impaired compared to the initial plans (pPlan). This resulted in higher actual lung doses than planned: V20Gy was 34.6 ± 6.8% instead of 32.8 ± 4.9% (p = 0.066), mean lung dose was 19.0 ± 3.1 Gy instead of 17.9 ± 2.5 Gy (p = 0.013). The generalized equivalent uniform dose (gEUD) of the lung was 18.9 ± 3.1 Gy instead of 17.8 ± 2.5 Gy (p = 0.013), leading to an increased lung normal tissue complication probability (NTCP) of 15.2 ± 13.9% instead of 9.6 ± 7.3% (p = 0.017). Weekly plan adaptation enabled decreased lung V20Gy of 31.6 ± 6.2% (−3.0%, p = 0.007), decreased mean lung dose of 17.7 ± 2.9 Gy (−1.3 Gy, p = 0.005), and decreased lung gEUD of 17.6 ± 2.9 Gy (−1.3 Gy, p = 0.005). Thus, resulting lung NTCP was reduced to 10.0 ± 9.5% (−5.2%, p = 0.005). Target volume coverage represented by conformity and homogeneity indices could be improved by weekly plan adaptation (CI: p = 0.007, HI: p = 0.114) and reached levels of the initial plan (CI: p = 0.721, HI: p = 0.333).ConclusionIGRT with CB-CT detects continuous GTV and PTV changes. CB-CT-guided ART for locally advanced NSCLC is feasible and enables superior sparing of healthy lung at high levels of plan conformity.

Deep learning methods for enhancing cone‐beam CT image quality toward adaptive radiation therapy: A systematic review

“…The primary motivation for improving CBCT image quality is to provide accurate pretreatment anatomical information to facilitate online ART. By minimizing inter‐fractional anatomic uncertainty, clinical benefits accrue from the reduction of dose to OAR and escalation of dose to target volumes 3,4,84–87 . The following discussion aims to summarize best practices that may be of interest to DL practitioners and inform clinicians on the current state of CBCT‐based ART.…”

PET/CT-based adaptive radiotherapy of locally advanced non-small cell lung cancer in multicenter yDEGRO ARO 2017-01 cohort study

“…Consistent with our data, no significant impact on OS could be shown. However, a safe RT-volume reduction with improved sparing of healthy lung is likely to results in lower toxicity [ 21 – 23 ].…”

“…At the time of enrollment to our study, sequential durvalumab maintenance implemented by the PACIFIC trial was not the standard of care for patients with inoperable stage III NSCLC, but needs to be taken into account today [ 23 ]. Importantly, PET/CT staging and treatment planning was not mandatory in the PACIFIC trial but should be considered standard of care based on our findings consistent with recent literature [ 11 , 28 ].…”

Magnetic resonance linear accelerator technology and adaptive radiation therapy: An overview for clinicians

“…This is primarily because the effort associated with the process is exceedingly time‐consuming with the current technology. Before sufficient support of that time and effort can be provided or more robust technologies become available, there should be commensurate compensation for the considerable additional time and effort associated with this work 42‐51 . Table 1 summarizes select prospective trials that have recently examined different adaptive strategies 35,37,38,41 …”