Implications of Pathologic Complete Response Beyond Mediastinal Nodal Clearance With High-Dose Neoadjuvant Chemoradiation Therapy in Locally Advanced, Non-Small Cell Lung Cancer

Optimal surgical timing and radiotherapy dose for trimodality therapy in locally advanced non‐small cell lung cancer

“…In terms of neoadjuvant RT dose, wide individual and institutional variability exists, 19 with some centers using 45 Gy, previously established in phase II and III cooperative group trials, [1][2][3]5 while others standardly employ dose escalation in the neoadjuvant setting. 4,20 As such, NCRT dose and TI to surgery are often determined by the physician and/or institutional preference, and they are not currently based on high-level evidence.…”

“…Notably, however, radiation dose did not independently predict of OS or postoperative mortality in this analysis. While radiation dose escalation in the neoadjuvant setting can improve the rate of neoadjuvant nodal clearance, 4,11 and while such higher radiation doses have led to notable survival times for trimodality patients at experienced centers, we recommend dose escalation above 50.4 Gy when treating on a clinical trial or at high volume thoracic centers with surgeons experienced with operating following higher neoadjuvant RT doses, as therapy at high volume centers correlates with superior OS for NSCLC patients treated with chemoradiation 28 and for patients with other thoracic malignancies treated with TMT. 29 Several limitations to our analysis exist.…”

“…Neoadjuvant therapy can help achieve negative-margin resections, downstage the type of surgery needed, and even increase the rates of pathological mediastinal downstaging, which correlates with improvements in overall survival (OS). 4 Although surgery after NCRT can improve progression-free survival (PFS) rates, this has not translated into an OS benefit to date. In phase III randomized prospective clinical trial, the benefit in PFS reported by Albain et al 5 was likely offset by a 26% postoperative mortality rate in pneumonectomy patients, leading to a lack of improved OS in the overall trimodality cohort.…”

“…Furthermore, 20.8% of patients with surgery >66 days received a radiation dose >60 Gy versus 8.6% in the surgery ≤66 days (p < 0.001). Having treatment with higher radiation dose 50 4. 60 Gy (HR 1.62 [1.22-2.15]; p < 0.001) and >60 Gy (HR 3.64 Note: Numbers might not sum to 100.0% due to rounding.…”

Mediastinal lymph node clearance and anti-PD-1 induction in resected NSCLC

“…Despite the impressive pathological remission rate of the primary tumor, comprehensive radiologic and pathologic analysis of the achieved mediastinal lymph node clearance (MC) was not described. A prognostic role of MC after induction therapy in resected node positive NSCLC is well established [2][3][4]. There is also evidence that residual nodal disease after multimodal induction has a negative impact on progression-free and overall survival.…”