Clinical Investigation
Progression of Non–Small-Cell Lung Cancer During the Interval Before Stereotactic Body Radiotherapy

Presented at the 51st annual meeting of the American Society for Therapeutic Radiology and Oncology, November 1–5, 2009, Chicago, IL, USA, and awarded the clinical first place poster prize.
https://doi.org/10.1016/j.ijrobp.2010.10.001Get rights and content

Purpose

To investigate the relationship between waiting time (WT) and disease progression in patients undergoing stereotactic body radiotherapy (SBRT) for lung adenocarcinoma (AD) or squamous cell carcinoma (SQ).

Methods and Materials

201 patients with Stage I AD or SQ undergoing SBRT between January 2004 and June 2010 were analyzed. The WT was defined as the interval between diagnostic computed tomography before referral and computed tomography for treatment planning or positioning before SBRT. Tumor size was measured on the slice of the longest tumor diameter, and tumor volume was calculated from the longest diameter and the diameter perpendicular to it. Changes in tumor volume and TNM stage progression were evaluated, and volume doubling time (VDT) was estimated.

Results

The median WT was 42 days (range, 5–323 days). There was a correlation between WT and rate of increase in volume in both AD and SQ. The median VDTs of AD and SQ were 170 and 93 days, respectively. Thirty-six tumors (23%) did not show volume increase during WTs >25 days. In 41 patients waiting for ≤4 weeks, no patient showed T stage progression, whereas in 25 of 120 (21%) patients waiting for >4 weeks, T stage progressed from T1 to T2 (p = 0.001). In 10 of 110 (9.1%) T1 ADs and 15 of 51 (29%) T1 SQs, T stage progressed (p = 0.002). N stage and M stage progressions were not observed.

Conclusion

Generally, a WT of ≤4 weeks seems to be acceptable. The WT seems to be more important in SQ than in AD.

Introduction

With the development and establishment of stereotactic body radiotherapy (SBRT), increasing numbers of patients with Stage I non–small-cell lung cancer (NSCLC) who are medically inoperable or refuse surgery are now treated with SBRT 1, 2, 3, 4, 5. In Japan in particular, the number of patients who are medically operable but choose SBRT seems to be rapidly increasing. Considering this increase in the number of patients, the capacity of facilities that provide SBRT is increasingly insufficient. Accordingly, the waiting time (WT) before initiation of SBRT seems to be increasing, especially in Japan.

In head-and-neck cancer, long WTs are known to adversely affect treatment outcome 6, 7; in a meta-analysis by Chen et al. (6), the relative risk of local recurrence was estimated to increase by 1.15 times if patients were required to wait for a month or longer before the initiation of definitive radiotherapy. By contrast, the influence of WT on the treatment of NSCLC on survival remains poorly understood, although many studies focusing on this issue have been performed. The British Thoracic Society recommended a WT of no longer than 4 weeks between acceptance onto a surgeon’s waiting list and thoracotomy in operable NCSLC patients (8). However, this recommendation was derived only from the analysis of expert committee reports and the clinical experience of respected authorities. Therefore, the length of time that is acceptable for Stage I NSCLC has not yet been clarified.

The objective of this study was to investigate the relationship between WT and tumor growth and TNM stage progression in patients with lung adenocarcinoma (AD) or squamous cell carcinoma (SQ) undergoing SBRT and to identify any possible differences between AD and SQ.

Section snippets

Patients

The data used in this study were obtained from patients enrolled in multi-institutional protocol-based SBRT studies. Preliminary results of the SBRT study have recently been reported (9). Between April 2004 and June 2010, 319 patients entered the SBRT study at three institutions in Nagoya, Japan. All these patients had Stage I (according to the 6th edition of TNM staging) NSCLC measuring 5 cm or less in maximum diameter at diagnosis. Staging procedures included chest and upper abdominal

Results

The patient and tumor characteristics are shown in the Table. T1 tumors constituted 81% of all ADs and 77% of SQs, with no significant difference (p = 0.57). Figure 1 shows the distribution of WT in all the patients. The median WT was 42 days (range, 5–323 days). The proportions of patients with a WT of less than 4, 4–8, and 8–12 weeks were 28%, 39%. and 18%, respectively. The patient who waited for 323 days had long been observed without any treatment before referral to our department.

Figure 2

Discussion

The clinical significance of WT in SBRT for Stage I NSCLC should be discussed with respect to primary tumor and metastatic disease. In Japan, SBRT is indicated only for Stage I NSCLC measuring ≤5 cm in maximum diameter in terms of health insurance coverage, so if the tumor grows to >5 cm during WT, such patients lose the opportunity to receive new treatment. Even in patients with smaller tumors, the tumor control probability decreases with increased tumor size. Therefore, we have used higher

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Supported in part by Grants-in-Aid for Scientific Research from the Japanese Ministry of Education, Culture, Sports, Science and Technology.

Conflict of interest: none.

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