Clinical outcomes and toxicity predictors of thoracic re-irradiation for locoregionally recurrent lung cancer

Abstract

Background and purpose: Thoracic re-irradiation may be an alternative treatment for lung cancer patients who develop intrathoracic locoregional recurrence without systemic progression. This study aimed to retrospectively assess locoregional control, clinical outcomes, and toxicities in lung cancer patients who received thoracic re-irradiation. Materials and methods: We retrospectively reviewed 50 lung cancer patients who received thoracic reirradiation using conventional photon radiotherapy (RT) and stereotactic body radiotherapy (SBRT) between 2009 and 2017. The correlations of clinicopathologic factors, treatment factors, and dosimetric factors of RT with time to local progression (TTLP), progression-free survival (PFS), and overall survival (OS) after starting thoracic re-irradiation were calculated using log-rank tests and Cox regression models. Results: The median re-irradiation dose in equivalent dose in 2-Gy fractions was 51.1 Gy, and the mean re-irradiation planning target volume was 201.58 ml. The median mean lung dose (MLD) was 4.18 Gy, and the total lung volumes receiving a dose of 5 Gy (lung V5) and of 20 Gy (V20) were 19.8% and 5.85%, respectively. The TTLP, PFS, and OS were 18.0, 5.9, and 25.1 months, respectively. Lung V5 (p < 0.001), V20 (p = 0.011), and MLD (p = 0.002) were significantly associated with grade 2 lung toxicity. Seven (14%) patients developed lethal lung events. Subsequent chemotherapy following thoracic reirradiation was significantly correlated with lethal lung events (p = 0.009). Conclusion: Promising local control can be achieved with thoracic re-irradiation in lung cancer patients with locoregional recurrence. However, unexpected lethal lung events may occur, especially in patients receiving systemic therapy following thoracic re-irradiation.

High Dose Thoracic Re-Irradiation and Chemo-Immunotherapy for Centrally Recurrent NSCLC

“…As for histology, the minimum proportion of NSCLC patients was 72% [25]. Although in 9 studies at least 66% of the patients had a performance score of 0-1, this was not specified in one study [26] and another summarized all patients with ECOG 0-2 [3]. All included studies listed the disease stages in detail-either at RT or at Re-RT.…”

“…The mPFS was 9 months (range: 4.5 [29]-16 [25]) and the mLRC was 12.1 months (range: 6.5 [27]-20 [30]). The median proportion of long-term survivors after re-irradiation was 39% (range: 15% [27]-50% [26]). Outcome data are summarised in Table 3.…”

“…Severe (grade 3-4), acute, and late toxicities were observed in 0% [30]-39% [3] and 0% [25,29] to 12 % [3], respectively. Seven studies reported therapy-related mortality between 2% [24,27] and 14% [26].…”

“…Prognostic and predictive variables for both clinical outcome (OS, PFS, LRC) and main toxicities, i.e., esophageal and pulmonary, are summarized in Table 5. If only the five studies that included multivariate analysis are considered [23,24,26,28,31], infield relapse combined with central tumor location [28] seemed to influence toxicity (p-value 0.03 HR 6.4). The following predictors and prognosticators for OS could be identified: PTV (p-value 0.000 HR 1.007) [24], histology (p-value 0.004 HR 0.4; p-value 0.04 HR 3.5) [11,23], cCRT (p-value 0.0045 HR 2.6 [11], re-irradiation dose (p-value 0.021 HR 0.2) [11], recurrent tumor size (p-value 0.001 HR 17.3) [23] and ECOG (p-value 0.028 HR 2.5) [11].…”

“…The following predictors and prognosticators for OS could be identified: PTV (p-value 0.000 HR 1.007) [24], histology (p-value 0.004 HR 0.4; p-value 0.04 HR 3.5) [11,23], cCRT (p-value 0.0045 HR 2.6 [11], re-irradiation dose (p-value 0.021 HR 0.2) [11], recurrent tumor size (p-value 0.001 HR 17.3) [23] and ECOG (p-value 0.028 HR 2.5) [11]. T4-stage (p-value 0.013 HR 3.5), cCRT (p-value 0.027 HR 0.5) [11] and extrathoracic disease (p-value 0.02 HR 2.9) [26] were found to predict PFS. Furthermore, LRC was influenced by cCRT (p-value 0.004 HR 6.5) [11], interval (p-value 0.012 HR 0.4) [11], histology (p-value 0.03, HR 3.7) [23], and recurrent tumor size (p-value 0.04 HR 0.2) [28].…”