The impact of overall treatment time on outcomes in radiation therapy for non-small cell lung cancer

doi:10.1016/S0169-5002(99)00113-0

Lung Cancer

Volume 28, Issue 1, April 2000, Pages 11-19

https://doi.org/10.1016/S0169-5002(99)00113-0 Get rights and content

Abstract

Purpose: A retrospective study was carried out to evaluate the impact of overall treatment time (OTT) on the results of radiation therapy for non-small cell lung cancer (NSCLC). Materials and methods: From Jan. 1990 to Dec. 1996, 256 patients with stages I–IIIb NSCLC entered this analysis. All patients received definitive radiotherapy. Biologically effective dose (BED) was used to standardize the irradiation effects. The correlation between OTT and local progression-free survival was analyzed by linear-regression and Cox proportional hazard models. The prognostic variables for survival and distant metastasis were also briefly studied. Results: OTT had been shortened in 64 patients because of an accelerated hyperfractionated irradiation, while OTT was prolonged in 114 patients due to interruptions of irradiation courses. The main causes of interruption were machine breakdown or delayed preparations of cerrobend block for boost fields (55%), holidays (11%) and treatment toxicity and side-effects (34%). Patients treated with prolonged OTT (>45 days) had significant poorer local progression-free survival than whom with OTT of ≤45 days, 1, 3 and 5 year actuarial local progression-free survivals being 49, 17 and 15% for the former, and 74, 35 and 25% for the latter, respectively (P<0.001). BED-T that contained the factor of OTT correlated directly to local controls, which implied that BED-T represented radiobiological effects accurately, in other words, OTT had played a role in determining the radiobiological effects. Linear-regression on 103 cases treated with BED of 80–85 Gy₁₀ showed that 3 year local progression-free survival decreased by 9% per week with prolongation of OTT, or vice versa it increased by 9% per week with shortening OTT in an OTT range of 30–76 days. Cox multivariate analyses confirmed that OTT was an independent prognostic factor for local controls. Conclusion: OTT may have played an important role in determining local controls in radiotherapy for NSCLC. One should always keep in mind to make the OTT as short as possible, provided the patients can tolerate it, and to reduce irradiation interruptions for whatever reasons to a minimum.

Introduction

Lung cancer has been a major cause of cancer related deaths in Shanghai since 1990. Its incidence had increased to 74.7/100 000 in males and 32.2/100 000 in females by 1996, ranking first and second, respectively in the incidence of malignancies [1]. Unfortunately, more than two-thirds of non-small cell lung cancer (NSCLC), when diagnosed, have been in middle or late stages. Thus, combining irradiation and chemotherapy would be the treatment of choice for these cases. Radiotherapy plays an important role as a treatment for locally advanced NSCLC, but local failure still occurs in 70–80% of the patients. In the past decade, a number of studies have shown that prolonged overall treatment time (OTT) was one of the major causes of failure in radiation therapy for several epithelial carcinomas, especially for squamous cell carcinomas of the head and neck [2], [3]. Accelerated repopulation of clonogenic tumor cells during the course of radiotherapy was assumed to account largely for the failures. Recently, some data has shown that a prolonged OTT resulted in poor local control in radiotherapy for NSCLC [4], [5]. In order to obtain the same biological effect, it was recommended that an extra dose of 0.45 Gy be added to the total radiation dose for each day of prolongation to compensate for the accelerated proliferation of tumor cells during a prolonged irradiation course [5]. Inversely, one could then assume that a shortened irradiation course, but still keeping the total irradiation dose high, or even higher than that generally used, would improve local controls for NSCLC. Based on the experience of the Cancer Hospital of Shanghai Medical University, this study has made a retrospective analysis of the correlation of OTT to the outcome of irradiation for NSCLC, emphasizing the influence of a shortened course on local control.

Section snippets

Patient eligibility for this study

1.
NSCLC patients treated by definitive radiotherapy.
2.
Histologically or cytologically proved.
3.
Karnofsky Performance Status (KPS)≥60.
4.
Stage I–IIIb (AJCC 1992), excluding the patients with malignant pleural effusion.
5.
Weight loss in 3 months prior to treatments<10%.
6.
Diameter of tumor on CT scan<10 cm.
7.
No previous malignant diseases.

Patients

From Jan. 1990 to Dec. 1996, 256 patients were eligible for the study. Among them, 123 patients were from two prospective clinical trials for non-small cell lung cancer, which

Local control

For overall group, the 1, 3 and 5 year overall actuarial local progression-free survivals were 54, 24 and 19%, respectively. To observe the impact of OTT on local control, the entire group was arbitrarily divided into two subgroups with OTT of 45 days as a cut-off. Forty-five days was the time needed to complete conventionally fractionated radiotherapy. The clinical characteristics were similar in two subgroups (Table 1). For the patients treated with OTT≤45 days, 1, 3 and 5 year actuarial

Discussion

The outcome of NSCLC is dismal for locally advanced NSCLC after combined therapy by irradiation and chemotherapy with 5-year survivals of around 5%. Although the predominant cause of deaths for NSCLC is believed to be distant metastases, local recurrence is still a major cause of failure. Animal experiments and clinical data in lung and prostate cancers indicated that improvements in local control would decrease distant metastases, as a part of the distant metastases was derived from local

Acknowledgements

This study was supported by a grant #9612 awarded by Shanghai Medical University, Shanghai.

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Citation Excerpt :
A link between a prolonged radiation treatment (RT) time (RTT) and inferior OS has been documented for other malignancies, such as head and neck (6, 7) and cervical (8) cancer. Several previous studies have suggested that a prolonged RTT can also negatively affect OS for patients with NSCLC (4, 9, 10). However, these analyses were limited by older treatment paradigms, the techniques used, and modest sample sizes.
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¹: Present address: Department of Radiation Oncology, Cancer Hospital, Sun Yat-Sen University of Medical Science, 651 Dong Feng Road, Guangzhou 510060, P.R. China.

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The impact of overall treatment time on outcomes in radiation therapy for non-small cell lung cancer

Abstract

Introduction

Section snippets

Patient eligibility for this study

Patients

Local control

Discussion

Acknowledgements

Int. J. Radiat. Oncol. Biol. Phys.

Int. J. Radiat. Oncol. Biol. Phys.

Int. J. Radiat. Oncol. Biol. Phys.

Int. J. Radiat. Oncol. Biol. Phys.

Int. J. Radiat. Oncol. Biol. Phys.