Grading of tumor regression in non-small cell lung cancer - Morphology andprognosis

Objective: Different types of multimodality therapy, including chemoradioth erapy and surgery, increasingly are being used for the treatment of patient s with locally advanced non-small cell lung cancer (NSCLC; stages IIIA and IIIB). In this context, the applicability of a morphologic regression gradi ng and its prognostic value were investigated. Patients and methods: In a multicenter phase II trial, 54 patients with loc ally advanced NSCLC received neoadjuvant bimodality treatment (ie, two cycl es of ifosfamide, carboplatin, and etoposide, followed by twice-daily radia tion up to 45 Gy with simultaneous administration of carboplatin and vindes ine). Forty patients underwent resections. Using the corresponding resectio n specimens of the primary and regional lymph nodes, the following regressi on grading was established: grade I, no regression or only spontaneous tumo r regression; grade II, morphologic evidence of therapy-induced tumor regre ssion with at least 10% (grade IIa) or < 10% (grade IIb) vital tumor tissue ; and grade III, complete tumor regression with no evidence of vital tumor tissue. Regression grading then was correlated with the survival time. Results: Three tumors were classified as regression grade I, 10 were classi fied as regression grade IIa, 20 were classified as regression grade IIb, a nd 7 were classified as regression grade III. Patients with tumors of regre ssion grades IIb or III showed significantly longer survival times than tho se with tumors of regression grades I or IIa (median survival time, 36 vs 1 4 months, respectively; 3-year survival rate, 52% vs 9%, respectively; p=0. 02). These survival times were also compared for patients who had undergone complete resection (median survival time, not reached vs 23 months, respec tively; 3-year survival rate, 56% vs 11%, respectively; p=0.03). The presur gical clinical response after patients had received neoadjuvant multimodali ty therapy had no predictive value in assessing the extent of therapy-induc ed tumor regression in the resection specimen. Conclusions: After neoadjuvant therapy of patients with NSCLC, the proposed tumor regression grading was of predictive value for long-term survival. B eyond the achievement of complete tumor resection (R0), a therapy-induced t umor regression of < 10% of vital tumor tissue is pivotal for superior long -term outcomes.