Is Molecular Remission as Detected by 18F-FDG PET/CT and Regression Grade After Neoadjuvant Treatment in the Primary Tumor and the Involved Mediastinal Lymph Nodes a Prognostic Factor in Patients With NSCLC Stage III?

Purpose/Objective(s)To evaluate the role of molecular remission as detected by 18F-FDG PET/CT and regression grade after neoadjuvant treatment followed by surgical resection of pts with NSCLC stage III.Materials/MethodsFor 76 pts with NSCLC stage IIIA (44%) / IIIB (56%) neoadjuvant treatment consisted of two to three cycles of chemotherapy (225 mg/m2 paclitaxel and carboplatin AUC 6 d1q21) and concomitant chemoradiation (50 mg/m2 paclitaxel and carboplatin AUC 2 d1, d8, d15; 1.5Gy b.i.d. up to 45 Gy). 15/28 pts with NSCLC stage IIIA (81%) / IIIB (19%) received three cycles of cisplatin 100 mg/m2 and docetaxel 85 mg/m2 d1q21 followed by radiation therapy (2 Gy up to 44 Gy), 13/28 pts only 3 cycles of chemotherapy as a sole neoadjuvant treatment. Documentation of involved lymph node stations as detected by 18F-FDG PET/CT and lymph node sampling during surgery according to the IASLC lymph node mapping (2009). Evaluation of histological regression grade (RG) according to Junker et al (2001) and correlation with 18F-FDG PET/CT for primary tumor and each lymph node station. Calculation of disease free survival using Kaplan-Meier estimates, log rank and chi square tests.ResultsActuarial tumor specific survival for the 76 pts with concomitant chemoradiation plus chemotherapy: complete vs incomplete metabolic remission prior to surgery after 60 months: 40% vs 24% (p = .018), RG III/IIb (no/less than 10% of vital tumor cells) vs RG IIa/I (more than 10% vital tumor cells) after 60 months: 46% vs 15% (p < .006). 42/76 (55%) pts had RG III/IIb, 20/76 (26%) pts had regression grade III. In 32/76 pts 18F-FDG PET/CT was correlated with the regression grade: 1/8 pts with RG III were in the 18F-FDG PET/CT false positive, 10 pts with RG IIb (i.e. all pts with RG IIb) were in the 18F-FDG PET/CT false negative, 1 pt with RG IIa was in the 18F-FDG PET/CT false negative: Hence, the cut-off level in detecting vital tumor cells by 18F-FDG PET/CT after neoadjuvant chemoradiation for NSCLC is about 10%. Actuarial tumor specific survival for the 28 pts with sequential chemoradiation or chemotherapy as a sole neoadjuvant treatment: RG III vs RG IIb/IIa/I after 60 months: 50% vs 16%. 05/28 (18%) pts had RG III. Assuming a pts number of 540, the treatment regimen consisting of concomitant chemoradiation plus chemotherapy might be superior to the other neoadjuvant treatment regimens.ConclusionsMolecular remission in mediastinal lymph nodes as detected by 18F-FDG PET correlates well with regression grade and both may predict (long-term) therapeutic outcome in pts with stage III NSCLC. The cut-off level in detecting vital tumor cells by 18F-FDG PET after neoadjuvant chemoradiation for NSCLC is about 10%. Our preliminary data of 104 pts suggest that intensification of neoadjuvant treatment may lead to a higher amount of complete remission resulting in an increased survival. However this hypothesis has to be tested in prospective trials. Purpose/Objective(s)To evaluate the role of molecular remission as detected by 18F-FDG PET/CT and regression grade after neoadjuvant treatment followed by surgical resection of pts with NSCLC stage III. To evaluate the role of molecular remission as detected by 18F-FDG PET/CT and regression grade after neoadjuvant treatment followed by surgical resection of pts with NSCLC stage III. Materials/MethodsFor 76 pts with NSCLC stage IIIA (44%) / IIIB (56%) neoadjuvant treatment consisted of two to three cycles of chemotherapy (225 mg/m2 paclitaxel and carboplatin AUC 6 d1q21) and concomitant chemoradiation (50 mg/m2 paclitaxel and carboplatin AUC 2 d1, d8, d15; 1.5Gy b.i.d. up to 45 Gy). 15/28 pts with NSCLC stage IIIA (81%) / IIIB (19%) received three cycles of cisplatin 100 mg/m2 and docetaxel 85 mg/m2 d1q21 followed by radiation therapy (2 Gy up to 44 Gy), 13/28 pts only 3 cycles of chemotherapy as a sole neoadjuvant treatment. Documentation of involved lymph node stations as detected by 18F-FDG PET/CT and lymph node sampling during surgery according to the IASLC lymph node mapping (2009). Evaluation of histological regression grade (RG) according to Junker et al (2001) and correlation with 18F-FDG PET/CT for primary tumor and each lymph node station. Calculation of disease free survival using Kaplan-Meier estimates, log rank and chi square tests. For 76 pts with NSCLC stage IIIA (44%) / IIIB (56%) neoadjuvant treatment consisted of two to three cycles of chemotherapy (225 mg/m2 paclitaxel and carboplatin AUC 6 d1q21) and concomitant chemoradiation (50 mg/m2 paclitaxel and carboplatin AUC 2 d1, d8, d15; 1.5Gy b.i.d. up to 45 Gy). 15/28 pts with NSCLC stage IIIA (81%) / IIIB (19%) received three cycles of cisplatin 100 mg/m2 and docetaxel 85 mg/m2 d1q21 followed by radiation therapy (2 Gy up to 44 Gy), 13/28 pts only 3 cycles of chemotherapy as a sole neoadjuvant treatment. Documentation of involved lymph node stations as detected by 18F-FDG PET/CT and lymph node sampling during surgery according to the IASLC lymph node mapping (2009). Evaluation of histological regression grade (RG) according to Junker et al (2001) and correlation with 18F-FDG PET/CT for primary tumor and each lymph node station. Calculation of disease free survival using Kaplan-Meier estimates, log rank and chi square tests. ResultsActuarial tumor specific survival for the 76 pts with concomitant chemoradiation plus chemotherapy: complete vs incomplete metabolic remission prior to surgery after 60 months: 40% vs 24% (p = .018), RG III/IIb (no/less than 10% of vital tumor cells) vs RG IIa/I (more than 10% vital tumor cells) after 60 months: 46% vs 15% (p < .006). 42/76 (55%) pts had RG III/IIb, 20/76 (26%) pts had regression grade III. In 32/76 pts 18F-FDG PET/CT was correlated with the regression grade: 1/8 pts with RG III were in the 18F-FDG PET/CT false positive, 10 pts with RG IIb (i.e. all pts with RG IIb) were in the 18F-FDG PET/CT false negative, 1 pt with RG IIa was in the 18F-FDG PET/CT false negative: Hence, the cut-off level in detecting vital tumor cells by 18F-FDG PET/CT after neoadjuvant chemoradiation for NSCLC is about 10%. Actuarial tumor specific survival for the 28 pts with sequential chemoradiation or chemotherapy as a sole neoadjuvant treatment: RG III vs RG IIb/IIa/I after 60 months: 50% vs 16%. 05/28 (18%) pts had RG III. Assuming a pts number of 540, the treatment regimen consisting of concomitant chemoradiation plus chemotherapy might be superior to the other neoadjuvant treatment regimens. Actuarial tumor specific survival for the 76 pts with concomitant chemoradiation plus chemotherapy: complete vs incomplete metabolic remission prior to surgery after 60 months: 40% vs 24% (p = .018), RG III/IIb (no/less than 10% of vital tumor cells) vs RG IIa/I (more than 10% vital tumor cells) after 60 months: 46% vs 15% (p < .006). 42/76 (55%) pts had RG III/IIb, 20/76 (26%) pts had regression grade III. In 32/76 pts 18F-FDG PET/CT was correlated with the regression grade: 1/8 pts with RG III were in the 18F-FDG PET/CT false positive, 10 pts with RG IIb (i.e. all pts with RG IIb) were in the 18F-FDG PET/CT false negative, 1 pt with RG IIa was in the 18F-FDG PET/CT false negative: Hence, the cut-off level in detecting vital tumor cells by 18F-FDG PET/CT after neoadjuvant chemoradiation for NSCLC is about 10%. Actuarial tumor specific survival for the 28 pts with sequential chemoradiation or chemotherapy as a sole neoadjuvant treatment: RG III vs RG IIb/IIa/I after 60 months: 50% vs 16%. 05/28 (18%) pts had RG III. Assuming a pts number of 540, the treatment regimen consisting of concomitant chemoradiation plus chemotherapy might be superior to the other neoadjuvant treatment regimens. ConclusionsMolecular remission in mediastinal lymph nodes as detected by 18F-FDG PET correlates well with regression grade and both may predict (long-term) therapeutic outcome in pts with stage III NSCLC. The cut-off level in detecting vital tumor cells by 18F-FDG PET after neoadjuvant chemoradiation for NSCLC is about 10%. Our preliminary data of 104 pts suggest that intensification of neoadjuvant treatment may lead to a higher amount of complete remission resulting in an increased survival. However this hypothesis has to be tested in prospective trials. Molecular remission in mediastinal lymph nodes as detected by 18F-FDG PET correlates well with regression grade and both may predict (long-term) therapeutic outcome in pts with stage III NSCLC. The cut-off level in detecting vital tumor cells by 18F-FDG PET after neoadjuvant chemoradiation for NSCLC is about 10%. Our preliminary data of 104 pts suggest that intensification of neoadjuvant treatment may lead to a higher amount of complete remission resulting in an increased survival. However this hypothesis has to be tested in prospective trials.