Clinical Investigation
Rapid Disease Progression With Delay in Treatment of Non–Small-Cell Lung Cancer

Presented at the 48th Annual Scientific Meeting of the American Society for Therapeutic Radiology and Oncology in Philadelphia, Pennsylvania, October 2006.
https://doi.org/10.1016/j.ijrobp.2009.11.029Get rights and content

Purpose

To assess rate of disease progression from diagnosis to initiation of treatment for Stage I-IIIB non–small-cell lung cancer (NSCLC).

Methods and Materials

Forty patients with NSCLC underwent at least two sets of computed tomography (CT) and 18-fluorodeoxyglucose positron emission tomography (PET) scans at various time intervals before treatment. Progression was defined as development of any new lymph node involvement, site of disease, or stage change.

Results

Median time interval between first and second CT scans was 13.4 weeks, and between first and second PET scans was 9.0 weeks. Median initial primary maximum tumor dimension (MTD) was 3.5 cm (0.6–8.5 cm) with a median standardized uptake value (SUV) of 13.0 (1.7–38.5). The median MTD increased by a median of 1.0 cm (mean, 1.6 cm) between scans for a median relative MTD increase of 35% (mean, 59%). Nineteen patients (48%) progressed between scans. Rate of any progression was 13%, 31%, and 46% at 4, 8, and 16 weeks, respectively. Upstaging occurred in 3%, 13%, and 21% at these intervals. Distant metastasis became evident in 3%, 13%, and 13% after 4, 8, and 16 weeks, respectively. T and N stage were associated with progression, whereas histology, grade, sex, age, and maximum SUV were not. At 3 years, overall survival for Stage III patients with vs. without progression was 18% vs. 67%, p = 0.05.

Conclusions

With NSCLC, treatment delay can lead to disease progression. Diagnosis, staging, and treatment initiation should be expedited. After 4–8 weeks of delay, complete restaging should be strongly considered.

Introduction

The natural history of untreated non–small-cell lung cancer (NSCLC) is poorly understood. The vast majority of patients with Stage I–III disease will receive some form of therapy, unless their general medical condition or shorter life expectancy precludes administration of treatment. Because of the aggressiveness of the disease with most patients receiving treatment, there are minimal data reported regarding observation alone (even for short time periods) without treatment. For medically inoperable Stage III NSCLC patients, one study reported a short median survival time of 14 months without treatment vs. 46 months and 21 months with surgery or conventional radiation therapy (RT), respectively (1). However, these data apply to medically inoperable patients with multiple medical comorbidities that may be unrelated to malignancy. In general, the consequences of declining treatment or inherent logistical delays in diagnosis or initiation of treatment remain unclear.

Cancer patients often inquire regarding the clinical impact of brief delays in treatment initiation. Depending on the histology, grade, stage, and other features of a malignancy, there can be vastly different natural progression patterns that may or may not have an impact on clinical outcome over a short period. However, if left untreated for a lengthy period, nearly all cancers progress locally or distantly, often leading to mortality. Therefore, expediting the process of diagnosis and subsequent prompt initiation of appropriate therapy should theoretically improve outcome. But what about patient-generated delays or the routine logistical delays of a health care system that are inherent to the process of diagnosis, staging workup, and initiation of treatment for NSCLC?

The purpose of this study was to analyze a cohort of NSCLC patients who underwent initial staging that included computed tomography (CT) and positron emission tomography (PET) scans and then subsequently received a second set of CT and PET scans after unintentional delay in treatment. We analyze the rate of clinical progression, upstaging, and distant metastasis over the time period between the two sets of scans in an attempt to quantify the risk of these events over time without intervening treatment.

Section snippets

Methods and Materials

Between 1999 and 2005, 40 patients with clinical Stage I–III NSCLC underwent at least two sets of staging CT and PET scans before any therapeutic intervention for their malignancy at William Beaumont Hospital, Royal Oak, MI. The first imaging studies were performed as part of a routine staging workup. Repeat staging studies were not planned. Instead, they were performed because of delay in the therapeutic intervention for various reasons or as part of the treatment planning process for RT.

Results

Patient characteristics are listed in Table 1. The distribution of tumor histology was roughly equivalent to the general population with adenocarcinoma and squamous cell carcinoma comprising 43% and 33% of tumors, respectively. As expected, most patients were diagnosed over the age of 60 years (80%). At the time of diagnosis, half of tumors were located in the right upper lobe. Thirty-eight percent of patients were considered to have clinical Stage I disease at the time of initial diagnosis.

Discussion

In this study, we analyzed 40 NSCLC patients who underwent initial staging including CT and PET scans and then also underwent subsequent restaging CT and PET scans before RT planning at varying time intervals from the initial staging studies. We found that clinical progression of disease occurred in 13% of patients at only 4 weeks. Clinical progression rates at 8 and 16 weeks were 31% and 46%, respectively. The likelihood of advancement in overall stage was 13% at 8 weeks and 21% at 16 weeks.

Conclusion

For patients with NSCLC, delays in initiation of definitive therapy can lead to significant disease progression. Diagnosis, staging, and initiation of treatment should be expedited for these patients. We recommend timely treatment but after 4–8 weeks of treatment delay, complete restaging should be strongly considered.

References (22)

  • Sazon DA, Santiago SM, Soo Hoo GW, et al. Fluorodeoxyglucose-positron emission tomography in the detection and staging...
  • Cited by (66)

    View all citing articles on Scopus

    Conflict of interest: none.

    View full text