Corsini Erin M, Weissferdt Annikka, Pataer Apar, Zhou Nicolas, Antonoff Mara B, Hofstetter Wayne L, Mehran Reza J, Rajaram Ravi, Rice David C, Roth Jack A, Vaporciyan Ara A, Walsh Garrett L, Cascone Tina, Heymach John V, Swisher Stephen G, Sepesi Boris
Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Eur J Cardiothorac Surg. 2021 Jan 4;59(1):100-108. doi: 10.1093/ejcts/ezaa290.
Major pathological response (MPR) is prognostic of outcomes for patients with non-small-cell lung cancer following neoadjuvant chemotherapy and is used as the primary end point in neoadjuvant immunotherapy trials. We studied the influence of pathological nodal disease on patterns and timing of recurrence among patients with MPR.
Patients treated with neoadjuvant chemotherapy for stages I-III non-small-cell lung cancer were identified. Surgical specimens were histopathologically examined for tumour viability, categorized as ≤10% viability (MPR) or >10% (NoMPR). Overall survival and disease-free survival were evaluated with emphasis upon MPR and pathological nodal disease.
Among 307 patients, 58 (19%) had MPR within primary tumour and 42 (14%) had MPRypN0. In the MPR group, the frequency of cN0 and cN+ disease was 18 (31%) and 40 (69%); similarly, the frequency of ypN0, ypN1 and ypN2 was 72% (42/58), 16% (9/58) and 12% (7/58), respectively. When evaluating only those with MPR, recurrence rates among those with MPRypN0, MPRypN1 and MPRypN2 were 33% (14/42), 44% (4/9) and 71% (5/7) (P = 0.16). The median time-to-recurrence in MPRypN0, MPRypN1 and MPRypN2 was 40, 10 and 14 months (P = 0.006). Distant recurrences were less common among those with MPRypN0 [MPRypN0, 26% (11/42); MPRypN1, 44% (4/9); MPRypN2, 71% (5/7); P = 0.047]. Though the median disease-free survival was prolonged among those with MPR vs NoMPR (120 vs 25 months, P < 0.0001), only those with MPRypN0 had prolonged disease-free survival in comparison to other groups upon pairwise comparisons, while MPRypN+ experienced no benefit.
MPRypN0 represents the most favourable surrogate end point following neoadjuvant chemotherapy. Patients with ypN1-2 are at the risk of early recurrence regardless of primary tumour MPR, warranting intensive surveillance and consideration for additional adjuvant therapy. We highlight that MPRypN0 is the most rigorous end point and should be considered as a surrogate end point in future neoadjuvant trials.
主要病理缓解（MPR）可预测非小细胞肺癌患者新辅助化疗后的预后，并且是新辅助免疫治疗试验的主要终点。我们研究了病理淋巴结疾病对MPR患者复发模式和时间的影响。
确定接受I-III期非小细胞肺癌新辅助化疗的患者。对手术标本进行组织病理学检查以评估肿瘤活性，分为活性≤10%（MPR）或>10%（无MPR）。评估总生存期和无病生存期，重点关注MPR和病理淋巴结疾病。
在307例患者中，58例（19%）原发肿瘤内有MPR，42例（14%）为MPRypN0。在MPR组中，cN0和cN+疾病的发生率分别为18例（31%）和40例（69%）；同样，ypN0、ypN1和ypN2的发生率分别为72%（42/58）、16%（9/58）和12%（7/58）。仅评估MPR患者时，MPRypN0、MPRypN1和MPRypN2患者的复发率分别为33%（14/42）、44%（4/9）和71%（5/7）（P = 0.16）。MPRypN0、MPRypN1和MPRypN2患者的复发中位时间分别为40、10和14个月（P = 0.006）。MPRypN0患者的远处复发较少见[MPRypN0为26%（11/42）；MPRypN1为44%（4/9）；MPRypN2为71%（5/7）；P = 0.047]。虽然MPR患者的无病生存期较无MPR患者延长（120个月对25个月，P < 0.0001），但两两比较时，只有MPRypN0患者与其他组相比无病生存期延长，而MPRypN+患者未获益。
MPRypN0是新辅助化疗后最有利的替代终点。ypN1-2患者无论原发肿瘤是否有MPR均有早期复发风险，需要加强监测并考虑进行额外的辅助治疗。我们强调MPRypN0是最严格的终点，应在未来的新辅助试验中作为替代终点考虑。
