Clinical Investigation
Potentially Curative Radiotherapy for Non–Small-Cell Lung Cancer in Norway: A Population-Based Study of Survival

https://doi.org/10.1016/j.ijrobp.2010.01.050Get rights and content

Purpose

The efficacy of curative irradiation in the treatment of non–small-cell lung cancer patients is considered limited. The purpose of this study was to evaluate long-term survival in a population-based approach.

Methods and Materials

Cases of non–small-cell lung cancer diagnosed from 1993 to 2001 were identified in the Cancer Registry of Norway. Electronic linkage with national data from the hospitals' radiotherapy verification systems identified those who received potentially curative doses (≥50 Gy). Hospital records were reviewed for all patients.

Results

A total of 497 patients (336 men) were identified with a radiation dose of ≥50 Gy delivered to the lung region. Of these, 41% received 60 Gy or more. The majority (70%) of patients included had advanced stage disease: 24% Stage IIIA and 46% Stage IIIB. The overall 1-, 3-, and 5-year observed survival rates were 53%, 16%, and 9%, respectively. Multivariable analyses identified stage and chemotherapy, but not radiation dose, as significant independent prognostic variables for survival. However, 68% of patients treated with chemotherapy participated in prospective studies with inclusion criteria that excluded patients with less favorable prognostic factors, leading to a selection bias. The number of fractions and the radiation doses varied widely among different hospitals.

Conclusion

The long-term prognosis after radiation therapy is poor. More sophisticated, targeted, and uniform delivery of radiation therapy is needed. The apparent benefit of chemotherapy may in part be due to selection of patients with more favorable prognostic factors for this therapy.

Introduction

Non–small-cell lung cancer (NSCLC) is associated with a poor long-term prognosis and accounts for more cancer-related deaths than any other cancer in the Western world. Patients with NSCLC who have technically inoperable tumors or who are unfit for surgery might be candidates for curative radiotherapy. For Stage I disease, a 5-year overall survival rate of more than 20% has been achieved, but local recurrence is the most common treatment failure (1). For patients with locally advanced NSCLC treated with radiotherapy alone, the 5-year survival is less than 10% (2). Without active treatment, patients would unlikely survive as long as 5 years (3).

Treatment results with conventional radiotherapy are clearly inferior to those obtained with surgery. In the absence of randomized trials, comparisons are complicated because of significantly more comorbidities among patients undergoing radiotherapy rather than surgery (4). From an ethical perspective, such randomized trials can hardly be performed for Stages I and II. Randomized trials and case series, however, have demonstrated comparable results of radiotherapy vs. surgery in subgroups of Stage IIIA-N2 patients and in elderly patients (5, 6, 7, 8, 9). Radiation doses of 50 Gy or more might be curative, but more radical doses ≥60 Gy are believed to result in increased long-term survival (10).

Radiotherapy techniques have improved substantially over the past few decades. More accurate planning and delivery of radiotherapy have made it possible to administer higher doses with more accurate targeting of the tumor (11). In Norway, the movement from two- to three-dimensional planning and treatment has been the most important technical improvement during this period, increasing target doses, reducing radiated lung volumes, and minimizing normal lung tissue exposure and, thus, side effects. Despite similar improvements, the local failure rate was 73% in a United States series of patients treated with three-dimensional conformal radiation therapy, with a tumor dose of 63–103 Gy (12).

Growing evidence for a more favorable survival prognosis with a combination of radiotherapy and chemotherapy evolved during the 1990s, and consensus was established, but the debate is still ongoing about the time at which chemotherapy should be administered (13).

Previous reports on survival after radiation therapy have primarily been institutional, and few studies have been population based (14, 15, 16). Accordingly, we assessed national data on the outcome of potentially curative radiotherapy and identified factors that may influence survival.

Section snippets

Methods and Materials

Since 1953, all newly diagnosed cases of cancer have been required by Norwegian law to be reported to the Cancer Registry of Norway. Reports are received from three sources: clinical reports, pathology reports, and the Cause of Death Registry of Statistics Norway. A thorough description can be accessed from the electronic annual report “Cancer in Norway 2006” (17). Since 1998, electronic discharge summaries with diagnoses and procedures for all hospital stays in Norway have been used to

Results

A total of 497 patients were treated with radiotherapy doses ≥50 Gy and were thus included in the analysis. Patient characteristics are presented in Table 1. There was a predominance of men (68%). The mean age was 66 years for men and 63 years for women, and one third of the patients had participated in randomized studies.

Radical radiotherapy was given at four centers during the entire period; one center started in 1995 and another in 1999. The mean delivered dose was 56.4 Gy (range, 50–74 Gy).

Discussion

The current study shows the limited long-term survival for patients receiving potentially curative doses of radiotherapy, which is consistent with previous reports (14, 26). Although the 5-year relative survival rate was only 10.1%, the 10-year relative survival rate was 5.7%, clearly demonstrating the curative potential of radiotherapy.

Only 4% of all NSCLC patients treated during the study period received radiotherapy with ≥50 Gy, although the use of radiotherapy increased sharply toward the

Conclusions

The long-term prognosis after radical radiotherapy does not seem to have improved during the last few decades. The overall 5-year observed survival rate is below 10%. More sophisticated and targeted delivery of radiation therapy is advocated. Although chemotherapy as evaluated in multivariable analysis seems to give a modest survival advantage, this result should be regarded with caution because younger patients with better prognosis within each stage group may have been selected for

Acknowledgments

The authors thank Dr. Christian Von Plessen and Øystein Fløtten for aid in collecting clinical data and Olaug Talleraas for help in preparing the data regarding radiotherapy.

References (36)

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Conflict of interest: none.

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