Lung Cancer in Young Adults* WJliam Bourke, M.B.; David Milstein, M.D.; Raffaele Giura, M.D.; Marco Donghi, M.D.; Maurizio Luisetti, M.D., F.C.C.P.; Ami-Hai E. Rubin, M.D., F.C.C.P.; and Lewis J Smith, M.D., F.C.C.P.

Objective: To de6ne tbe basis for tbe conflicting reports on the prognosis of lung cancer in young adults. De.ign: Retrospective review of lung cancer patients between 1977 and 1988. Setting: Medical centers in Chicago (Northwestern Memorial Hospital), northern Israel (Rambam Medical Center), and northern Italy (S. Anna and U. of Pavia Hospitals). Fbtienta: Patients were :S45 years of age with a diagnosis of primary lung cancer identi6ed from tumor registry records, pathology reports, and hospital charts, plus a sample of patients >45 years of age. Meaaurementa and Main Baulta: In Chicago, younger patients had a higher incidence of chest pain, fever, and neurologic symptoms at presentation than tbe older patients, and fewer were asymptomatic. They also had more lower lobe lesions on chest roentgenogram, a higher incidence of adenocarcinoma, more advanced disease, an increased likelihood of receiving chemotherapy, and reduced survival (p80 percent). However, there were differences in symptoms (generally more frequent in the Israeli patients), cell type (increased incidence of adenocarcinomas and decreased incidence of squamous cell carcinomas in Chicago and Israeli but not Italian patients), treatment (no therapy given to a greater proportion of the Italian patients), and most importantly survival (best in the Israeli patients, worst in the Italian patients). These findings support earlier studiesl. 4 •6 •12 that suggested that younger and older patients with lung cancer have different clinical features, pathologic findings, and prognosis. However, in two distinct and widely separate regions (Chicago and northern Israel), the prognosis in the younger patients was quite different. Those from Chicago had a rather poor prognosis, while in those from Israel the prognosis was significantly better. What factors may be responsible for the difference in survival between younger and older patients with lung cancer in the same region and between young patients with lung cancer from different regions? Cell type and stage of disease at presentation are two CHEST I 102 I 6 I DECEMBER, 1992

1727

characteristics of lung cancer that may explain the observed differences in survival. Younger patients in both Chicago and Israel had an increased incidence of adenocarcinomas and decreased incidence of squamous cell carcinomas compared with the older patients. Several studies have suggested that patients with adenocarcinoma of the lung have a worse prognosis than those with squamous cell tumors. 22 •23 Yet, the younger patients from Chicago did worse, while those from Israel did better than the respective older patients. Further, younger patients from Italy had a much lower proportion of adenocarcinomas, while their survival was as bad or worse than that seen in Chicago. Thus, cell type alone does not explain the differences in survival between the younger and older patients in this study. In Chicago, the difference in survival between younger and older patients was due, at least in part, to the more advanced stage of disease in the younger patients. Cox regression analysis revealed that stage of disease was the single most important determinant of prognosis. Age, when analyzed alone, was also a good prognostic indicator, but it added little to that provided by stage of disease. Because the number of patients available for analysis, especially with stage I or II disease, was small, it is possible that age would be an independent determinant if more patients were studied. The Israeli data are also consistent with disease stage being more important than age since survival was excellent in the younger patients with stage I or II disease. Several factors may contribute to the advanced stage oflung cancer in younger patients from Chicago, including a long duration of symptoms before presentation and a high incidence of lower lobe lesions. The long duration of symptoms may reBect the reluctance of both patients and physicians to consider the diagnosis oflung cancer in younger individuals. Since lung cancer occurs most frequently in the upper lobes, 24 a diagnosis oflung cancer in younger patients with lower lobe lesions may not be made as quickly as in those with upper lobe lesions. Another possible explanation for the survival differences is the treatment given. There were differences in treatment at the same center between age groups and between centers for the same age group. Approximately one half of the younger Chicago patients received chemotherapy, in contrast to only 15 percent of the older patients. In Israel and Italy, nearly one half of the patients received chemotherapy regardless of their age. Radiation was used extensively in both age groups in Chicago, somewhat less frequently in Israel, and only rarely in the Italian patients. There were also differences in the proportion of patients receiving only supportive care. About 20 percent of the older patients in Israel and the younger patients 1728

in Italy did not receive surgery, radiation, or chemotherapy. The most effective form of therapy for lung cancer is surgery. Surgery was performed on nearly the same proportion of younger patients at all three locations (23 to 35 percent). At least 80 percent of patients with stage I or II disease had surgical resection of the tumor. Therefore, the treatment received does not appear to explain the difference in survival between the younger patients, especially those with early stage disease, from the three locations. However, it may have contributed to the difference in survival between the younger and older patients in the same location since in both Chicago and Israel surgery was performed more frequently in the group with the better outcome. Factors other than extent of disease (stage) and therapy may have an inOuence on the survival of lung cancer patients. Initial performance status and weight loss are considered to be important prognostic factors. Previous studies at our institution in Israel have shown that the most important prognostic factors are brain metastases, age older than 60 years, performance status, weight loss, and stage of disease. 25 As one of these factors, performance status, was not evaluated in the present study, it is possible that its distribution at the various centers could explain some of the differences in the results. We found a high incidence of adenocarcinoma in the younger patients from both Chicago and Israel and in the older patients from Chicago, nearly all of whom were smokers. The incidence of adenocarcinoma of the lung has been increasing for the last 40 years. 17•18 Although originally thought not to be related to cigarette smoking, it is now well accepted that smoking is a risk factor for its development. 26 •27 The increasing incidence of adenocarcinoma of the lung in the general population can be partly explained by its greater frequency in women 16 who comprise a growing proportion of the lung cancer population. 5 •17•19•00•28 A relationship between cell type and sex may explain the low incidence of adenocarcinoma in the Italian patients, as only 10 percent of the patients were female. However, it is not a satisfactory explanation for the results from the other two centers. In Chicago, there were fewer women in the younger age group, yet the younger group had a higher incidence of adenocarcinoma. In Israel, the percentage of women was the same in both age groups, but the incidence of adenocarcinoma was again higher in the younger patients. Further, there are data indicating that the incidence of adenocarcinoma of the lung is increasing in men as well as in women. 17 At the present time we are unable to explain the high incidence of adenocarcinoma in younger patients from both Chicago and Israel. The data from northern Italy differ from those of the Lung Cancer in Young AduHs (Bourlce eta/)

other two centers in several respects: a higher proportion of male subjects, squamous cell tumors, and stage I or II disease. Although a comparable group of patients >45 years of age was not available for study, comparisons can be made with data reported by Roviaro et al 11 from Milan, which encompasses the same region of northern Italy. They also found that more than 90 percent of their patients were male, squamous cell carcinoma was the predominant cell type, and a large proportion of patients had early-stage disease at presentation. They did not find differences in these and other parameters, including survival, between the younger patients and a group of older patients. However, their younger patients had a better 5year survival (21 percent) than the Italian patients in our study. The basis for this difference is unclear. Finally, we must consider that male-female differences in the different age groups and regions may be responsible for some of our findings. McDuffie et al 16 reported data from Saskatchewan, Canada that showed that male and female patients develop different types of lung cancer (female patients have more adenocarcinomas and large-cell anaplastic tumors) and that female subjects appear to develop lung cancer at an earlier age with less smoking exposure. As already noted, our data indicate that the higher incidence of adenocarcinoma in younger patients is not due to the presence of more women in the younger age group. In neither Chicago nor Israel was there a higher proportion of women in that group. Since we do not have detailed smoking data for the patients from all areas, we cannot comment on the increased susceptibility of women to cigarettes. Nonetheless, male-female differences do not appear to explain the differences we found between age groups. In conclusion, we have reviewed the characteristics of patients with lung cancer who were younger than or equal to 45 years of age at the time of diagnosis. This study is unique in that these patients came from three geographically distinct areas. There were similarities and differences between age groups from the same region and within the same age group in different regions. The most striking finding was the variable prognosis of younger patients, which appeared to be due, at least in Chicago and northern Israel, to the stage of the disease at the time the diagnosis was made. Identification of the basis for the differences in clinical characteristics and survival within and between populations may provide clues to the genetic and environmental factors responsible for the development oflung cancer, its different presentations, and its prognosis. ACKNOWLEDGMENTS: We wish to thank Michele Parker for her invaluable help in analyzing the data from Chicago via the Cox regression model.

REFERENCES

2 Denelfe G, Laquet LM, Verbeken E, Vermant G. Surgical treatment of bronchogenic carcinoma: a retrospective study of 720 thoracotomies. Ann Thorac Surg 1988; 45:380-83 3 Weiss W. Operative mortality and five year survival rates in men with bronchogenic carcinoma. Chest 1974; 66:483-87 4 Antkowiak JG, Regal A, 'Thkita H. Bronchogenic carcinoma in patients under age 40. Ann Thorac Surg 1989; 47:391-93 5 McDuffie HH, Klaassen OJ, Dosman JA. Characteristics of patients with primary lung cancer diagnosed at age 50 or younger. Chest 1989; 96:1298-1301 6 DeCaro L, Benfield JR. Lung cancer in young persons. J Thorac Cardiovasc Surg 1982; 8:372-76 7 Kyriakos M, Webber B. Cancer of the lung in young men. J Thorac Cardiovasc Surg 1974; 67:634-37 8 Ganz PA, Vernon SE, Preston D, Coulson WF. Lung cancer in younger patients. West J Med 1980; 133:373-78 9 Seddon OJ, Partridge MR. Carcinoma of the bronchus in young adults. Br J Clin Pract 1990; 44:24-5 10 Tsugane S, Watanabe S, Sugimura H, Arimoto H, Shimosato Y, Suemasu K. Smoking, occupational, and family history in lung cancer patients under 50 years of age. Jpn J Clin Oncol 1987; 17:309-17 11 Roviaro GC, Varoli F, Zannini P, Fascianelli A, Pezzuoli G. Lung cancer in the young. Chest 1985; 87:456-59 12 Pemberton JH, Nagorney OM, Gilmore JC, Taylor WF, Bernatz PE. Bronchogenic carcinoma in patients younger than 40 years. Ann Thorac Surg 1983; 36:509-15 13 Mountain CF. A new international staging system for lung cancer. Chest 1986; 89:225S 14 Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. JAm Stat Assoc 1958; 53:457-81 15 Cox DR. Regression models and life tables (with discussion). J R Stat Soc, Series B 1972; 34:187-220 16 McDuffie HH, Klaassen OJ, Dosman JA. Female-male differences in patients with primary lung cancer. Cancer 1987; 59:1825-30 17 Vincent RG, Pickren Jw. Lane WW, et al. The changing histopathology oflung cancer. Cancer 1977; 39:1647-55 18 Wu AH, Henderson BE, Thomas DC, Mack TM. Secular trends in histologic types of lung cancer. J Nat! Cancer Inst 1986; 77:53-6 19 McDuffie HH, Klaassen OJ, Dosman JA. Determinants of cell type in patients with cancer of the lung. Chest 1990; 98:1187-93 20 Kabut GC, Wynder EL. Lung cancer in non-smokers. Cancer 1984; 53:1214-21 21 Kreyberg L. Lung cancer and tobacco smoking in Norway. Br J Cancer 1955; 9:495-509 22 McKneally MF. Lung cancer in young patients. Ann Thorac Surg 1983; 36:505-07 23 Read RC, Schaefer R, North N, Walls R. Diameter, cell type, and survival in stage I primary non-small cell lung cancer. Arch Surg 1988; 123:446-49 24 Byrd RB, Carr DT, Miller WE, et al. Radiographic abnormalities in carcinoma of the lung as related to histological cell type. Thorax 1969; 24:573-75 25 Milstein D, Sapir D, Cohen Y, Robinson E. Prognostic factors in patients with lung cancer. lsr J Med Sci 1988; 24:588-92 26 Brownson RC, ReifJG, Keefe TJ, Ferguson SW, Pritzl JA. Risk factors for adenocarcinoma of the lung. Am J Epidemiol 1987; 125:25-34 27 Suzuki T, Sobue T, Fujimoto I, Doi 0, Thteshi R. Association of adenocarcinoma of the lung with cigarette smoking by grade of differentiation and cell type. Cancer Res 1990; 50:444-47 28 Wynder EL, Covey LS, Mabuchi K. Lung cancer in women: present and future trends. J Natl Cancer lnst 1973; 51:391-401

1 Putnam JS. Lung carcinoma in young adults. JAMA 1977; 2.18:35-6 CHEST I 102 I 6 I DECEMBER, 1992

1729

Lung cancer in young adults.

To define the basis for the conflicting reports on the prognosis of lung cancer in young adults...
5MB Sizes 0 Downloads 0 Views