Research Article: Late-Course Adaptive Adjustment Based on Metabolic Tumor Volume Changes during Radiotherapy May Reduce Radiation Toxicity in Patients with Non-Small Cell Lung Cancer

Date Published: January 26, 2017

Publisher: Public Library of Science

Author(s): Linlin Xiao, Ning Liu, Guifang Zhang, Hui Zhang, Song Gao, Zheng Fu, Suzhen Wang, Qingxi Yu, Jinming Yu, Shuanghu Yuan, Gabriele Multhoff.

http://doi.org/10.1371/journal.pone.0170901

Abstract

To reduce the high risk of radiation toxicity and enhance the quality of life of patients with non-small cell lung cancer (NSCLC), we quantified the metabolic tumor volumes (MTVs) from baseline to the late-course of radiotherapy (RT) by fluorodeoxyglucose positron emission tomography computerized tomography (FDG PET-CT) and discussed the potential benefit of late-course adaptive plans rather than original plans by dose volume histogram (DVH) comparisons. Seventeen patients with stage II-III NSCLC who were treated with definitive conventionally fractionated RT were eligible for this prospective study. FDG PET-CT scans were acquired within 1 week before RT (pre-RT) and at approximately two-thirds of the total dose during-RT (approximately 40 Gy). MTVs were taken as gross tumor volumes (GTVs) that included the primary tumor and any involved hilar or mediastinal lymph nodes. An original plan based on the baseline MTVs and adaptive plans based on observations during-RT MTVs were generated for each patient. The DVHs for lung, heart, esophagus and spinal cord were compared between the original plans and composite plans at 66 Gy. At the time of approximately 40 Gy during-RT, MTVs were significantly reduced in patients with NSCLC (pre-RT 136.2±82.3 ml vs. during-RT 64.7±68.0 ml, p = 0.001). The composite plan of the original plan at 40 Gy plus the adaptive plan at 26 Gy resulted in better DVHs for all the organs at risk that were evaluated compared to the original plan at 66 Gy (p<0.05), including V5, V10, V15, V20, V25, V30 and the mean dose of total lung, V10, V20, V30, V40, V50, V60 and the mean dose of heart, V35, V40, V50, V55, V60, the maximum dose and mean dose of the esophagus, and the maximum dose of the spinal-cord. PET-MTVs were reduced significantly at the time of approximately 40 Gy during-RT. Late course adaptive radiotherapy may be an effective way to reduce the dose volume to the organs at risk, thus reducing radiation toxicity in patients with NSCLC.

Partial Text

Lung cancer is the leading cause of cancer death[1]. Approximately 80% to 85% of lung cancer cases are non-small cell lung cancer (NSCLC). Of these cases, over 60% of patients require radiation therapy (RT) during the course of the disease[2]. In recent years, despite modern radiotherapy technologies, such as three-dimensional conformal radiation therapy (3D-CRT) and/or intensity modulation radiation therapy (IMRT), one treatment of 2 Gy is given daily 5 days per week for a total of 60+ Gy over 6+ weeks. The 5-year survival rate of NSCLC is approximately 15–20%[3]. Recent studies have shown that the incidence of severe radiation-induced lung toxicity (RILT) (Grade ≥ 3) is approximately 2.2–18%, and the incidence of radioactive esophagitis (Grade ≥ 3) is approximately 12.5%-34%[4,5,6]. This may be due to unknown changes in the tumor and normal tissues biological characteristics and function during therapy. Recent studies have demonstrated that, compared with prior to radiotherapy, the tumor size, shape, position, biological activity and normal tissue function may change and even cause tumor target and important organ damage in the middle of RT. Therefore, it is necessary to make comprehensive assessments during RT.

Radiotherapy is the main local treatment for patients with inoperable stage II-III NSCLC, and an adequate dose is essential for treatment success as increased radiation doses have been associated with reduction in the risk of death[7]. However, most patients with stage III NSCLC cannot receive an adequate dose for tumor control without exceeding the “safe” dose limits of the adjacent critical structures, such as the lung, esophagus, heart and spinal cord. An accurate definition of a target is crucial for the delivery of high-precision radiotherapy in NSCLC. We used FDG-PET to assess the tumor and normal tissues biological characteristics and function during RT. Meanwhile, FDG-PET could play an important role in lymph node staging by accurately showing positive nodes. However, PET helped to differentiate tumors and collapsed lungs, allowing a more accurate radiation volume of the lung. To redirect the remaining treatment, FDG PET-CT scans were repeated at approximately two-thirds of the total dose during-RT (approximately 40 Gy).

This study indicated that PET-MTVs may be reduced significantly at the time of approximately 40 Gy during RT, and late course adaptive radiotherapy may be an effective way to reduce the dose volume to the organs at risk. This could reduce radiation-induced injury in patients with NSCLC. More prospective studies on FDG PET-CT scans are ongoing in our institution.

 

Source:

http://doi.org/10.1371/journal.pone.0170901