Clinical Investigation
Quantification of Tumor Volume Changes During Radiotherapy for Non–Small-Cell Lung Cancer

https://doi.org/10.1016/j.ijrobp.2008.07.063Get rights and content

Purpose

Dose escalation for lung cancer is limited by normal tissue toxicity. We evaluated sequential computed tomography (CT) scans to assess the possibility of adaptively reducing treatment volumes by quantifying the tumor volume reduction occurring during a course of radiotherapy (RT).

Methods and Materials

A total of 22 patients underwent RT for Stage I-III non–small-cell lung cancer with conventional fractionation; 15 received concurrent chemotherapy. Two repeat CT scans were performed at a nominal dose of 30 Gy and 50 Gy. Respiration-correlated four-dimensional CT scans were used for evaluation of respiratory effects in 17 patients. The gross tumor volume (GTV) was delineated on simulation and all individual phases of the repeat CT scans. Parenchymal tumor was evaluated unless the nodal volume was larger or was the primary. Subsequent image sets were spatially co-registered with the simulation data for evaluation.

Results

The median GTV reduction was 24.7% (range, −0.3% to 61.7%; p < 0.001, two-tailed t test) at the first repeat scan and 44.3% (range, 0.2–81.6%, p < 0.001) at the second repeat scan. The volume reduction was not significantly different between patients receiving chemoradiotherapy vs. RT alone, a GTV >100 cm3 vs. <100 cm3, and hilar and/or mediastinal involvement vs. purely parenchymal or pleural lesions. A tendency toward a greater volume reduction with increasing dose was seen, although this did not reach statistical significance.

Conclusion

The results of this study have demonstrated significant alterations in the GTV seen on repeat CT scans during RT. These observations raise the possibility of using an adaptive approach toward RT of non–small-cell lung cancer to minimize the dose to normal structures and more safely increase the dose directed at the target tissues.

Introduction

The current treatment paradigm for advanced non–small-cell lung cancer (NSCLC) is combination chemoradiotherapy, either alone or followed by surgical resection in selected patients 1, 2, 3, 4. The overall survival rates remain low for these patients, with local control a significant problem. The data suggest that dose escalation yields improved local control; however, it has been limited by normal tissue toxicity 5, 6, 7, 8. The advent of three-dimensional conformal radiotherapy (RT) has allowed for dose escalation to tumor volumes while limiting the dose to normal lung parenchyma. However, there is still room for improvement in this regard. Efforts have been underway to further improve the therapeutic ratio in RT (RT) for NSCLC, most specifically with respect to quantifying tumor motion and volume changes throughout the treatment course. With this information, the treatment margins could theoretically be decreased, or individually tailored, allowing for dose escalation and/or a reduction of treatment morbidity.

It has been well demonstrated from experience using induction therapy before surgery that tumors respond within a short time to either chemoradiotherapy or RT alone. The timing of this response has not been well elucidated. The increasing use of respiration-correlated four-dimensional (4D) computed tomography (CT) for quantitative analysis has allowed for more precise assessment of this phenomenon. If decreases in tumor size were to occur during the RT course, this might be one method of reducing the volume of normal tissue irradiated. In this study, we sought to quantify the degree of tumor volume change during the RT course, with the goal of assessing whether adaptive RT using such changes might be worthy of additional exploration in patients with NSCLC.

Section snippets

Methods and Materials

Between September 2005 and June 2007, 22 patients who treated for Stage I-III NSCLC were evaluated with repeat CT scans during the RT course. Most patients had locally advanced squamous cell carcinoma that was treated with concurrent chemotherapy (Table 1). All patients received definitive therapy, except for 1, who was treated preoperatively. Radiotherapy was delivered in 2-Gy daily fractions to a median dose of 62 Gy (range, 50–74). The patients were treated with photon energies of 6 and/or

Results

One-half (50%) of the tumors evaluated were parenchymal and the remainder were mediastinal (14%), hilar/perihilar (32%), or chest wall (5%) tumors (Table 1). The lymph node volumes were evaluated in addition to the primary lesion in 2 patients, for a total of 24 volumes analyzed. The median initial tumor volume was 81.72 cm3, and the mean was 149.36 cm3 (range, 7.37–916.35). Chemotherapy was given concurrently in 15 patients, most of whom received cisplatin/etoposide or carboplatin/paclitaxel (

Discussion

Using repeat kilovoltage spiral CT scans taken at two points in the RT course for NSCLC patients, we have recorded substantial reductions in the radiologic extent of disease occurring during treatment. On average, the GTV was reduced to 44% of its original volume after 50 Gy of RT. Of the 22 patients studied, more than one-half had locally advanced disease. All were treated with standard fractionation, and all but 1 with definitive intent. Both reassessments were made during period in which

Conclusion

The results of this study have demonstrated significant alterations in GTV seen on repeat CT scans during a RT course. Our data revealed a mean decrease in the initial GTV of 30% by a nominal dose of 30 Gy and 43% by a nominal dose of 50 Gy. These observations raise the possibility of using an adaptive approach toward RT of NSCLC to minimize the dose to normal structures, as well as to more safely increase the dose directed at the target tissues. The need for expeditious planning in response to

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