Wei Li, Wenzhao Zhong, Xuening Yang, Riqiang Liao, Qiang Nie, 

Song Dong, Jin-ji Yang, Yilong Wu

Guangdong Lung Cancer Institute, Guangdong General Hospital

Objective:The progression of pulmonary ground glass nodules (GGNs) was slow, 5 years survival rate of lobe/sublobe resection was close to 100%. In clinical, we also found that the progression of some patients with advanced lung cancer was relatively slow and the prognosis was good. This part of the patients were often with intrathoracic disseminated lesions, and with the characteristics of late appearance of lymph nodes and distant metastasis. This study analysed the clinical, pathological and molecular characteristics of three different processes of intrathoracic disseminated lung cancer.

Method: Patients of postoperative recurrent M1a(r-M1a), intrathoracic accidental invisible M1a(s-M1a) and clinical diagnosis of M1a(c-M1a) and received TKI were retrospectively collected. Including general data, pathological subtype, stage, N status, comprehensive treatment and molecular profiles. Progression-free survival (PFS) and overall survival (OS) were evaluated by Kaplan–Meier and Cox regression models. 

Result: 1. r-M1a: From 2005.01 to 2009.12, postoperative recurrent M1a of Guangdong Lung Cancer Institute was 59 (2.4%), postoperative pathological stage of I/II/III was 30/8/21, respectively. The average progress to M1a was 25.0 months. From the progression of M1a, median OS(OS1) was 34.0 months (95%CI, 26.4-41.6). And the total OS was 71.0 months (95%CI, 58.8-83.2). OS1 was similar to stage IIB (31.0 months) of the 7th edition of the TNM classification of malignant tumors. Postoperative stage N0 and N1/2 were 33 and 26, respectively. The average progress to M1a of these two groups was 23.0 VS 27.0 months (P=0.205). From the progression of M1a, median OS of these two groups was 38.0 VS 27.0 months (P=0.059). And the total OS of these two groups was 76.0 VS 61.0 months (P=0.341). 2. s-M1a: From 2007.08 to 2013.06, consecutive lung cancer patients receiving thoracotomies at Guangdong Lung Cancer Institute were retrospectively analyzed. Fifty-eight patients (3.9%) receiving incomplete resections (R1/R2) were enrolled, including 38 patients with local residual cancer (stage IIIB, 2.6%) and 20 patients with disseminated pM1a (stage IV, 1.3%). Median PFS for the local residual and disseminated pT4-M1a groups was 9.0 and 18.0 months, respectively (95% CI, 5.285–16.715, P=0.099). Median OS was 15.0 and 45.0 months, respectively (95% CI, 18.972–39.028, P=0.001). Cox regression analysis revealed that group was the only independent prognostic factor (P=0.044) for OS. Compared to the local residual group, the disseminated pT4-M1a group contained more females (P=0.002), more patients younger than 60 years of age (P=0.028), more non-smokers (P=0.037), more adenocarcinomas (20/20 vs. 20/38, P<0.001), more adenocarcinomas with lepidic pattern (11/20 vs. 4/38, P<0.001), higher CEA levels (P=0.06), higher EGFR mutation rates (16/20 vs. 7/38, P<0.001), a higher R2/R1 resection ratio (P=0.013), a higher advanced stage IV/IIIB ratio (P<0.001), but fewer lymph node metastases (P=0.013). 3. c-M1a: From 2007.01 to 2012.12, 232 consecutive lung cancer patients receiving TKI at Guangdong Lung Cancer Institute were analyzed. Median PFS of receiving TKI was 9.0 months, and median PFS for Iressa group (120) and Erlotinib group (112) was both 9.0 months. Median PFS for 77 cases was longer than 1 year, including 27 cases of M1a (35.1%); Median PFS for 27 cases of M1a and other 50 cases was both 18.0 months, while median OS was 36.0 and 26.0 months, respectively (P=0.072). Median PFS for 16 cases was longer than 2 years, including 6 cases of M1a (37.5%). Three modes of TKI resistance were found as follows: 130 patients with dramatic progression, 42 with gradual progression, and 55 with local progression. Median PFS for the dramatic progression, gradual progression, and local progression groups was 9.3, 12.9 and 9.2 months, respectively (P=0.007). Median OS was 17.1, 39.4 and 23.1 months, respectively (P<0.001). However, M1a proportion of these three groups was 11/130, 13/42 and 3/55 (P<0.001), gradual progression group had the most of M1a. 

Conclusion: r-M1a, s-M1a and c-M1a were three different processes of intrathoracic disseminated lung cancer with similar clinical and pathological features. The progression of M1a was relatively slow in advanced lung cancer and it might be a distinct lung cancer subtype with a favorable prognosis. The characteristics of intrathoracic disseminated lung cancer in clinical and genetic aspects need further exploration.

Key Words: intrathoracic disseminated  slow growing