Optimizing treatment scheme for stereotatic treatment with cyberknife in lung cancer patients by analyzing radiobiological parameters determined by tumour locations

Abstract

Objectives: Lung cancer is the leading cause of cancer mortality in the world. Stereotactic Body Radiation Therapy (SBRT) is a novel technique in treatment of inoperable Non-Small Cell Lung Cancer (NSCLC) in which a high dose delivery of 8-30Gy radiation to the lung tumour with one to five fractions precisely, simultaneously, avoiding as much normal tissue as possible.

In the present pilot study, lungs were evenly divided into three parts in cranio–caudal direction, namely Upper Lung, Middle Lung and Lower Lung. As different risk organs are adjacent to different parts of lung, the different radiobiological responses in those risk organs have to be considered in treatment. This study is aimed to determine which dose-fractionation scheme is optimal for each spatial group of 6 patients with radiobiological approach in CyberKnife SBRT treatments. The result can act as a preliminary information for large scale study for establishing a NSCLC treatment protocol to benefit patients with better tumour control but less side effect, hence better quality of life after treatment.

Material and Methods: 18 NSCLC patients were retrospectively studied and re-planned with CyberKnife treatment planning system. Each spatial group included six patients. Radiobiological factors including Tumour Control Probability (TCP) and Normal Tissue Complication Probability (NTCP) with Biologically Effective Dose (BED) correction in Universal Survival Curve model (USC) were considered in each plan for heart, spinal cord, esophagus and lungs. Seven commonly clinically used dose-fraction schemes were ranked in each spatial group with Uncomplicated Tumour Control Probability scoring approach. Dosimetric parameters according to Task Group 101 of the American Association of Physicists in Medicine: Volume limits in maximum dose and threshold dose for esophagus, rib, heart, lung, spinal cord, ascending and descending aortas, trachea, and bronchus of each plan were also calculated as supporting information.

Results: In radiobiological approach, significant NTCPs (6.2% - 98.2%; mean 55.9%) were found in the ipsilateral lung among all schemes. At the upper lung group, a patient was with 7.0% and 5.7% spinal cord NTCPs and another patient was with 70.9% and 78.4% esophageal NTCPs in the schemes of 3x22Gy and 5x15Gy respectively. The NTCPs of contralateral lung and heart in all spatial groups were negligible. The mean TCP values varied between schemes of lowest BED (5x10Gy) and highest BED (3x22Gy) from 94.1% to 100.0% respectively. In dosimetric approach, if high BED scheme (>106Gy) was applied, few patients may develop Grade3+ complications on bronchus in Upper and Middle lung groups; on spinal cord in Upper and Lower lung groups; and on great vessels in Upper lung group. The low BED schemes such as 3x16Gy and 5x10Gy were relatively safe in all groups. Dose-fractionation scheme of 5x10Gy is the best compromise of TCP and NTCP in all Upper Lung Group, Middle Lung Group and Lower Lung Group (p<0.05). These radiobiological results were in good agreement with dosimetric results.

Conclusions: By analyzing the NTCPs and TCPs, 5x10Gy is optimal for all lung group patients. The result can be considered as a reference for large sample scale study in future.