Lung ART: Nodal Burden Best Guide For Predicting PORT Benefit

Author: By Lynda Williams, Senior medwireNews Reporter 

medwireNews: Postoperative conformal radiotherapy (PORT) protects patients with resected stage IIIAN2 non-small-cell lung cancer (NSCLC) against mediastinal relapse (MR), and nodal burden is the best predictor of this benefit, the latest Lung ART trial findings suggest. 

Cécile Le Pechoux, from Institut Gustave Roussy in Villejuif, France, reported the update for the phase III trial at the ESMO Congress 2021. 

Overall, 252 patients with completely resected NSCLC and proven N2 involvement were randomly assigned to receive conformal PORT at a dose of 54 Gy over 5.5 weeks, while 249 patients were not given the radiotherapy regimen. Chemotherapy before or after surgery, or no chemotherapy at all, was permitted.  

The investigator noted that around 90% of patients had undergone lobectomy or bilobectomy and 10% pneumonectomy, and most had received preoperative chemotherapy. In addition, 96% of the patients assigned to receive PORT completed treatment. 

Cécile Le Pechoux reminded delegates that, after a median 4.8 years of follow-up, the primary endpoint of disease-free survival (DFS) was previously reported to be a median 30.5 months with PORT and 22.8 months without, giving a nonsignificant hazard ratio (HR) of 0.86. The corresponding 3-year DFS and overall survival rates were comparable between the arms at 47.1% versus 43.8%, and 66.5% versus 68.5%, respectively. 

For the current presentation, the investigator reported that MR occurred in significantly fewer PORT-treated patients than controls (25 vs 46%, HR=0.45), but a comparable proportion of patients in the two groups experienced distant metastases (60 vs 49%) and brain metastases (24 vs 18%). And patients in the PORT group were significantly more likely to die than controls (15 vs 5%, HR=2.63). 

On further examination, patients were most likely to experience first MR in their initially involved nodes, and this occurred in 66% of cases in the PORT group and 47% of cases among controls.  

The presenter said that for right-sided tumours, MR occurred most commonly in the 4R (48%) and 2R (44%) stations versus the 7 (47%) and 4L (42%) stations for left-sided stations but noted that the MR “eventually […] recur[s] in the contralateral nodes.” 

DFS events were significantly predicted by the presence of N2 involvement that included N1 involvement (HR=1.50 vs no N1 involvement), by having two or more mediastinal lymph node stations involved (HR=1.46 vs 0 stations), and by failure to achieve a R0 resection (HR=1.29–1.95 for R-uncertain to R2 surgery). 

By contrast, female sex and squamous cell carcinoma histology were protective factors against DFS events, said Cécile Le Pechoux. 

Overall, there was no significant difference between the PORT and no PORT treatment groups with regard to the 3-year distant metastasis-free survival rates (68.47 vs 72.31%) but 3-year MR-free survival was significantly better with PORT (86.06 vs 72.26%, HR=0.45). 

While patients with the heaviest burden of lymph node disease, defined as lymph node ratio greater than 25% and at least two nodes involved, had no significant DFS survival benefit from PORT, patients with a lower burden derived a significant 3-year mediastinal relapse-free benefit from PORT (HR=0.45), as did patients without extracapsular extension (HR=0.46). 

Cécile Le Pechoux summarised that DFS prognostic factors were “mainly based on nodal involvement”, adding that “there is no robust evidence of predictive factors for PORT on DFS components.” 

She therefore concluded that “personalised prescription of PORT should be based on prognostic factors of relapse and a joint assessment of toxicity and efficacy.” 

Reference 

1170O - Le Pechoux C, Barlesi F, Pourel N, et al. An international randomized trial, comparing post-operative conformal radiotherapy (PORT) to no PORT, in patients with completely resected non-small cell lung cancer (NSCLC) and mediastinal N2 involvement: Characterisation of PORT efficacy in lung ART (IFCT-0503, UK NCRI, SAKK). Annals of Oncology 2021:32(suppl_5):S939-S948. doi: 10.1016/annonc/annonc728