Clinical evaluation of stereotactic radiation therapy for recurrent or second primary mediastinal lymph node metastases originating from non-small cell lung cancer

Abstract

Aims: To evaluate the safety and efficacy of stereotactic radiotherapy (SRT, both stereotactic body RT [SBRT] and fractionated stereotactic RT [FSRT]) in the treatment of patients with recurrent or second primary mediastinal lymph node metastases (R/SP-MLNMs) originating from non-small cell lung cancer (NSCLC).

Methods: Between 10/2006 and 7/2013, patients with R/SP-MLNMs originating from NSCLC were enrolled and treated with SRT at our hospital; their data was stored in prospectively-collected database. The enrolled patients were divided into Group A (without prior RT) and Group B (with prior RT). The primary end-point was overall survival (OS). The secondary end-points were the MLNM local control (LC), the time to symptom alleviation, and toxicity using the Common Terminology Criteria for Adverse Events (CTCAE v4.0).

Results: Thirty-three patients were treated (16 in Group A with 19 R/SP-MLNMs and 17 in Group B with 17 R/SP-MLNMs). For the entire cohort, the median OS was 25.5 months with a median follow-up of 20.9 months (range, 3.2-82). The 1-year and 3-year actuarial LC rates were 100% and 86%, respectively. Symptom alleviation was observed in 52% of patients, after a median of 6 days (range, 3-18). CTCAE v4.0 ≥ Grade 3 toxicities occurred in 5 patients (15%; all in Group B); among them, Grade 5 in 2 patients.

Conclusions: We recommend exercising extreme caution in using SRT for R/SP-MLNMs in patients who received prior RT (particularly to LN station 7). For patients without previous RT, SRT appears to be safe and efficacious treatment modality; prospective studies are warranted.

Keywords: fractionated stereotactic radiation therapy; local control; mediastinum; non-small cell lung cancer; stereotactic body radiation therapy.

Conflict of interest statement

CONFLICT OF INTEREST STATEMENT

No benefits in any form have been or will be received from a commercial party directly or indirectly related to the subject of this article.

Figures

Figure 1. A comparison of treatment machines and fractionation options in external beam radiation therapy (EBRT) for non-small cell lung cancer (NSCLC)

Legend: typically, in the primary treatment of NSCLC, EBRT is delivered as conventionally fractionated RT (CFRT), which is 1.8 – 2.0 Gy per day, one fraction per day, for a total of ~30 fractions, to a total dose of ~60 Gy; CFRT is delivered with intensity modulated RT (IMRT). Stereotactic radiation therapy (SRT) is a type of EBRT that delivers RT accurately and precisely to the tumor, more so than CFRT with IMRT. SRT may be used for small (i.e. T1-2) or recurrent / second primary mediastinal lymph node metastases (R/SP-MLNMs, as in the current work). SRT is divided into stereotactic body RT (SBRT, the delivery of 3.5-15 Gy per fraction, in 5 fractions or less) and fractionated stereotactic RT (FSRT, in more than 5 fractions). SRT may be delivered with a gantry-based LINAC or with a robotic arm LINAC (i.e. a CyberKnife).

Figure 2. Representative planning CT and isodose distributions with SRT of patients with R/SP-MLNMs originating from NSCLC

The purple and yellow lines indicate GTV and PTV, respectively. (A-I) The LN stations of MLNMs. CT: computer tomography; SRT: stereotactic radiotherapy; R/SP-MLNM: recurrent / second primary mediastinal lymph node metastases; GTV: gross tumor volume; PTV: planning target volume.

Figure 3. Analysis of SRT, IMRT, and the composite images for a representative patient

In this case, a 64-year-old woman squamous cell lung cancer located in left lower lobe with station 7 MLN, received SRT 6.8 months after completion of IMRT;. Unfortunately, the patient died of tracheoesophageal fistula six weeks after completion of SRT. (A) IMRT was delivered in in 28 fractions to a dose of 61.6 Gray for NSCLC of LN station 7; (B) At 6.8 months after completion of IMRT, there was a R-MLNM at station 7; SRT was initiated, in 8 fractions to 48 Gy, prescribed to the 75% isodose line; (C) Composite plans were created of SRT and IMRT using MIM Software. SRT: stereotactic radiotherapy; IMRT: intensity modulated radiation therapy.

Figure 4. The detailed summary of the prescribed dose, dose per fraction, and BED10 from each MLNM stations

BED10: biologically effective dose at an α/β of 10; R/SP-MLNMs: recurrent or second primary mediastinal lymph node metastases; Gy: Gray; f: fraction.

Figure 5. Actuarial OS of patients

(A) OS after receiving SRT; (B) OS after receiving SRT depending on treatment group (Group A is without prior RT; Group B is with prior RT); (C) OS after receiving SRT, depending on the time between surgery and SRT; (D) OS after receiving SRT, depending on R- vs. SP-MLNMs. OS: Overall survival; R/SP-MLNM: recurrent /second primary mediastinal lymph node metastases; SRT: stereotactic radiation therapy; S: surgery; IT: interval time.