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Exclusive High-Dose Rate Brachytherapy (HDR-BT) for Limited Non-small Cell Lung Carcinoma: Results of a French Study in 199 Patients

Reviewer: Charles Wood, MD
Abramson Cancer Center of the University of Pennsylvania
Ultima Vez Modificado: 19 de octubre del 2005

Presenter: M.A. Mahe
Presenter's Affiliation: Radiotherapy, Centre Oscar Lambret, Lille, France
Type of Session: Scientific

Background

The standard of care for treatment of early stage lung cancer is surgery with or without chemotherapy. HDR-BT is an alternative option for patients with contraindications to surgery. This study was undertaken to evaluate the efficacy and toxicity of HDR-BT in non-operable endobronchial carcinoma patients.

Materials and Methods

• Eligible patients included those with non-obstructing endobronchial non-small cell lung cancer amenable to fiberoptic bronchoscopy and not able to be treated by surgical resection or external beam radiotherapy
• Radiotherapy generally consisted of 30 Gy delivered in 6 weekly fractions of 5 Gy each, prescribed to a 1 cm radius from the bronchial catheter
• The Kaplan-Meier method was used to calculate survival curves and was compared with the Logrank test
• Cox models were employed to perform uni- and multivariate analyses on the following prognostic factors: tumor location (lobar or segmental versus main stem bronchus), previous treatment with surgery and/or external beam radiation versus none, in situ versus invasive histology, total dose 30 Gy versus less, fraction size 5 Gy versus more, number of catheters (1 versus 2)

Results

• 199 patients (196 male, 3 female) with a mean age of 64.9 years (range 40-84) were treated in 8 radiation centers between 4/91 and 5/04
• The majority of tumors were squamous cell carcinoma (97%) and in a lobar or segmental location (89%); clinical staging was as follows:
  • 53 patients with Tis
  • 133 patients with T1
  • 9 patients with T2
  • 4 patients with TX
• 42 patients (25%) had received prior external radiation for lung cancer, and 70 (42%) had received prior surgery for lung cancer
• The majority of patients received 30 Gy (68%) in 5 Gy fractions (64%) via 1 catheter (44%)
• Mean follow-up from treatment was 30.5 months (range 9-116)
• Histologic evaluation performed in 108 patients 3 months post-treatment revealed a complete response in 94% of patients
• 91 patients (46%) are alive with no evidence of disease
• Of the 108 patients (54%) who have died, 38 died secondary to intercurrent disease, 27 secondary to local failure, 9 secondary to distant failure, 10 secondary to local and distant failure, 12 secondary to treatment-related complications, and 12 from an unrelated cause
• 2 and 5 year overall survival (OS) are 58% and 31%, respectively, with a median survival of 28.6 months
• 2 and 5 year disease-specific survival (DSS) are 85% and 68%, respectively
• 2 and 5 year local relapse-free survival (LRFS) are 74% and 63%, respectively
• Acute toxicity included pneumothorax (1.5%) and mucosal inflammation (10%)
• Late toxicity included hemoptysis (7% with 5% fatal), bronchitis (21%), and necrosis (3.5%)
• Univariate analysis revealed:
  • Improved OS, DSS, and LRFS for lobar/segmental location (p=0.0005)
  • Improved OS for 5 Gy fractions (p=0.02)
  • Improved OS for no prior external radiation (p=0.04)
  • Improved LRFS for use of 2 catheters (p=0.01)
• Multivariate analysis revealed:
  • Improved OS (p=0.001), DSS (p=0.04), and LRFS (p=0.01) for lobar/segmental location
  • Improved LRFS for use of 2 catheters (p=0.02)
• No prognostic factor was found to influence frequency of complications

Author's Conclusions

• HDR-BT was demonstrated to have reasonable efficacy and safety
• Main stem bronchus lesions might be better treated with external beam radiation
• Future work will center on the use of multiple catheters for improved dosimetry and CT imaging for improved targeting

Clinical/Scientific Implications

This large, multicenter, retrospective study detailed the use of high-dose rate brachytherapy as a single modality in patients with non-obstructing endobronchial lung cancers who were not amenable to either surgery or radiation. This study involves a very narrow therapeutic window, as is reflected in the relatively long time period required to treat nearly 200 patients. A majority of the patients had received prior radiation or surgery secondary to lung cancer, and it is unclear what classified the patients in the study group to be considered unfit for additional surgery or conformal radiation. More data is required to determine what patient factors might predict for treatment-related complications. Further study is certainly warranted with this modality, and it would be particularly interesting to determine how high-dose rate brachytherapy compares to other local modalities that would theoretically be offered as options to this patient population, such as photodynamic therapy and repeated laser excision.