Our study demonstrated the clinical presentations, and EGFR mutation status, in young patients with advanced NSCLC, a relative rare patient population with many differences from the older patient population. We also found that low BMI, stage IV disease, anemia at diagnosis, and male gender were the negative prognostic factors, which seldom investigated in previous literatures. These findings may improve comprehension of this special patient population.
Younger patients had higher rate of adenocarcinoma (57.5-77.9%)[4
]. Our study showed that adenocarcinoma was the predominant histologic type in young patients; of both genders. The reason for the extremely high percentage of adenocarcinoma in young patients has been seldom studied and requires more attention. As compared with older patients, a higher female percentage in young patients was presented in several studies (36.1-48.7%)[4
]; however most studies have shown that males were the predominant gender, except for studies in Taiwan (51.8-52.5%) [6
], as well as in our study (51.4%). This might be related to the ethnicities of patients and environmental effects [20
The outcomes of young and old patients with lung cancer had been previously studied, but the results were inconsistent [5
]. Most studies compared only the outcomes of younger and older patients, but not the outcomes of different age groups. Our study showed that the median OS of patients aged ≤45
years was significantly shorter than that of patients aged between 46 and 55
years and was longer than that of patients aged ≥76
years. No significant difference was found when we compared the median OS of young patients with the patients aged between 55 to 65 and 66 to 75
years. A similar result was obtained in a recent Chinese study.[4
]. The explanation for the survival difference remains unclear.
The influence of BMI has been studied in several types of cancers. In gynecological malignancies, a high BMI is associated with a higher incidence of cancer but better disease-specific survival [21
]. Similar results have also been found for gastric cancer and renal cell carcinoma [23
]. However, high BMI is a poor prognostic factor in breast cancer [25
]. Obese patients may have better nutritional resources to withstand the stress of cancer metastasis and cachexia [28
Little is known about the association between prognosis and BMI in lung cancer. In epidemiology studies, obese patients had lower lung cancer mortality; however, the mechanism is unknown [29
]. A recent study by Yang et al
. showed that patients who were obese at the time of lung cancer diagnosis had a longer median survival for all cancer stages and histologic subtypes [32
]. The obesity paradox is that being overweight increases the incidence of heart failure, but in patients with chronic heart failure, obesity is associated with better survival. This phenomenon appears to also apply to diseases with high catabolic states, such as chronic kidney disease, rheumatoid arthritis and lung cancer [32
Hematologic abnormalities, including anemia, have been reported as prognostic factors in many solid tumors [35
]. In our study, anemia was shown to be an independent negative prognostic factor. The incidence of anemia in lung cancer patients varies from 6.5% to 34% [38
]. Lung cancer patients presenting with anemia have an increased 19% risk of death [40
]. However, erythropoietin treatment of anemic cancer patients has failed to demonstrate survival benefits and may even harmful [41
]. It should be noted that anemia could merely reflect the disease severity, rather than the direct cause of mortality [40
The frequency of EGFR
mutation in adenocarcinoma showed wide variation among different reports (3%-59.7%); this was related to ethnicity, gender, and smoking status [19
]. Several studies, in which East Asia was the focus, have shown that the EGFR
mutation rate in NSCLC was about 26% to 38.6%, and the mutation rate increased 32% to 55% in adenocarcinoma [19
]. However, there is a paucity of data regarding the EGFR
mutation status in young patients. Our study showed that the EGFR
mutation rate was 50.0% in advanced cases of NSCLC and 51.8% in cases of adenocarcinoma. The mutation rate was relatively high; these results could be attributed to the high percentage of female patients and fewer numbers of smokers among young patients.
Of the patients with positive EGFR
mutations, patients who received EGFR-TKI had a longer PFS as compared to patients who received chemotherapy. This result is compatible with the Iressa Pan-Asia study and a phase 3 clinical trial conducted by the North-East Japan Study Group [46
]. However, the median PFS and survival time in the EGFR-TKI group of our study were only 6.0 and 19.9
months, respectively. This was clearly shorter than the corresponding values obtained in a phase 3 trial in Japan (PFS, 10.8
months; survival time, 30.5
]. Similar results with a shorter PFS were also observed for the chemotherapy group (this study vs. phase 3 trial in Japan, 4.0 vs. 5.4
]. This suggests that the young patients with advanced lung adenocarcinoma have a poorer treatment response compared to the general population, especially with regard to EGFR-TKI.
There are several limitations to this study. First, the study was retrospective in design and included a relatively small case number. Second, because only a relatively small number of patients received EGFR mutation analysis, the results of EGFR mutation and EGFR-TKI treatment in the young lung cancer patients should be interpreted carefully.