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Characteristics and outcomes of patients with unresected early-stage non-small cell lung cancer.

ABSTRACT

Background. This study describes the characteristics, management, and outcomes of patients with unresected early-stage non-small cell lung cancer (NSCLC).

Methods. A retrospective review was conducted to identify all patients with unresected stage I or stage II NSCLC diagnosed between 1990 and 1998.

Results. Ninety-seven patients were identified who met our criteria. The median age at diagnosis was 68 years; 78% of patients were white, 81% were male, 81% had stage I disease, and 67% had squamous cell carcinoma. Cancer-specific treatment, including chemotherapy, radiation therapy, and combined chemotherapy and radiation therapy, was administered to only 27 patients. The median survival time was 22 months for the treated group and 11 months for the untreated group.

Conclusion. The majority of patients with unresected early-stage NSCLC do not receive cancer therapy. They should be thoroughly considered for treatment, however, especially in light of recent advances in surgery and radiation therapy, and the development of more active, less toxic chemotherapeutic agents.

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APPROXIMATELY 169,500 AMERICANS were predicted to be diagnosed with lung cancer in 2001, with 157,400 persons dying of that disease. (1) A 5-year survival rate of less than 15%, combined with the high incidence, makes lung cancer the leading cause of cancer deaths in the United States. Different therapeutic modalities are used in the management of lung cancer, depending upon tumor stage and the patient's clinical status.

Surgical resection remains the primary treatment for early stages of non-small cell lung cancer (NSCLC), especially stages I and II. (2-5) Many patients with early stages of NSCLC are not candidates for surgery. Additional patients and physicians decide against surgery because of complicated socioeconomic factors. (6,7) The characteristics and outcomes of patients who do not undergo surgery have not been thoroughly studied, and the management of these patients is not well defined.

This study analyzes the characteristics and outcomes of early-stage lung cancer patients who did not undergo surgical resection, and the impact of other cancer-specific therapy on their outcomes. The possible impact of recent therapeutic developments on the management of these patients is also discussed.

MATERIALS AND METHODS

Patient Selection

This study included all patients with stages I and II NSCLC diagnosed between 1991 and 1998 who did not undergo surgical resection of their cancer. These patients were seen at the University of Arkansas for Medical Sciences and Little Rock Veterans Affairs Hospital.

Study Design

Data were obtained by review of medical records, tumor registry information, pathology reports and slides, and radiology reports. The data collected included patient characteristics, such as age, race, sex, date of diagnosis, tumor site, type of treatment, type of relapse or recurrence, and cause of death. Other cancer data collected included histologic subtype, tumor size, and primary tumor/regional lymph node/ metastasis (TNM) stage. Comorbid conditions and the forced expiratory volume in 1 second ([FEV.sub.1]) were also included.

Statistical Analysis

Patient demographics and medical characteristics were summarized using descriptive statistics. Overall survival-time estimates for each group were obtained using Kaplan-Meier (product-limit) methodology, and distributions of survival time were compared using log-rank tests. P [greater than or equal to] .05 was considered statistically significant. Analyses were done using SAS/ STAT software, Version 7 (SAS Institute Inc, Cary, NC).

RESULTS

A total of 97 patients were included in this study. Median age of these patients was 68 years (range, 40 to 84 years); 81% were male, and 78% were white (Table). The majority of the patients had stage I disease (81%) and squamous cell carcinoma histology (67%). Tissue diagnosis was obtained by bronchoscopy in 74% of the patients, fine needle aspiration in 21%, and sputum cytology in 5%. Median follow-up was 11 months (range, 1 to 110 months). The reasons patients did not have surgery were poor pulmonary function (n = 71), patient refusal (n = 11), and chronic debilitating illness (n = 15). Seventy patients (72%) had no treatment for their cancer. The remaining 27 patients had various cancer-specific treatments, including chemotherapy (n = 12), radiation therapy (n = 2), and combined chemotherapy and radiation therapy (n = 13). The chemotherapy regimens included cisplatin and etoposide (n = 12), carboplatin and etoposide (n = 2), carboplatin and paclitaxel (n = 5),and others (n = 6).

No significant difference in age was noted between the 2 groups, with a median age of 67 years (range, 40 to 79 years) for the treated patients and 69 years (range, 43 to 84 years) for untreated patients. There was no significant difference in the [FEV.sub.1] levels between the 2 groups. Median [FEV.sub.1] for the treated group was 1.13 L (range, 0.52 to 2.03 L), compared with 1.25 L (range, 0.45 to 2.73 L) for the untreated cohort.

The patients who received treatment had a median overall survival time of 22 months (range, 3 to 110 months), with 7 patients (26%) alive at the time of analysis. None of the patients in the untreated group were alive at the time of analysis, and their median survival time was 11 months (range, 1 to 43 months) (P = .008) (Figure). The cause of death was cancer related in 86% of the patients, unrelated to cancer in 3%, and unknown in 11%.

DISCUSSION

The lung cancer cure rate is stage dependent, with earlier stages having higher cure rates. This is mainly attributed to the efficacy of surgery in attaining cure in many patients with early-stage disease; however, up to one third of patients with early-stage lung cancer do not have surgery. (6-8) Our study population represents 17% of all patients with stages I and II NSCLC seen at our institutions. Apparently, smoking not only contributes to cancer occurrence, but also leads to other illnesses, including pulmonary dysfunction, that make treating the cancer difficult. The commonly quoted survival rates of early-stage lung cancer are usually exaggerated, due to reporting single-institution experiences on selected patient populations. If all patients with early stage NSCLC were included, the survival rate of patients with early lung cancer would not be as high. (6,9)

The management of patients with unresected stages I and II NSCLC is not well defined. Radiation therapy is the most common modality studied in this setting, with 5-year survival rates ranging from 6% to 40% (10-14) These studies generally include both inoperable and unresectable locally advanced lung cancer, which makes the study group heterogeneous. Furthermore, the denominators are usually missing from these studies; in other words, the percentage of patients who did not receive treatment, for whatever reason, is unknown. Our study shows that 1 of 6 patients with stage I or II NSCLC did not have surgery, and almost three fourths of those patients did not receive any therapy at all. While this study does not absolutely prove that all patients with unresected lung cancer will benefit from other cancer-specific treatment, it should at least encourage physicians to thoroughly consider treating these patients. Revisiting the management approach of these patients is warranted for many reasons. First, new surgical techniques, such as video-assisted thoracic surgery, are less traumatic than thoracotomy. (15-18) Second, the role of volume-reduction surgery in patients with severe emphysema warrants evaluating some lung cancer patients for this type of surgery, which could improve their underlying pulmonary disease and cure their cancer. (19,20) Third, improvement in imaging techniques, such as positron emission tomography and 3-dimensional treatment planning, enables physicians to administer higher doses of radiation with more precision, thereby minimizing toxicity to the normal tissues. (21-23) Finally, the development of more effective, less toxic chemotherapeutic agents may make concurrent therapy in these patients more feasible.
TABLE

Patient Characteristics (N = 97)

 Characteristic No. (%)

Age [greater than or equal to]65 70 (72)
Male sex 79 (81)
White race 76 (78)
Stage I 79 (81)
Histology
 Squamous cell carcinoma 65 (67)
 Adenocarcinoma 13 (14)
 Large cell carcinoma 5 (5)
 Poorly differentiated carcinoma 13 (14)
 Mixed histology 1 (1)
Forced expiratory volume in
 1 second ([FEV.sub.1])
 <1 liter 40 (41)
 1-2 liters 47 (49)
 >2 liters 10 (10)


References

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(2.) Flehinger BJ, Kimmel M, Melamed MR: The effect of surgical treatment on survival from early lung cancer: implication for screening. Chest 1992; 101:1013-1018

(3.) Read RG, Shaefer RC, North N, et al: Diameter, cell type, and survival in stage I primary non-small cell lung cancer. Arch Surg 1988; 123:446-449

(4.) Martini N, Burt ME, Bains MS, et al: Survival after resection of stage II non-small cell lung cancer. Ann Thorac Surg 1992; 54:460-465

(5.) Pairolero PC, William DE, Bergstralh EJ, et al: Postsurgical stage I bronchogenic carcinoma: morbid implications of recurrent disease. Ann Thorac Surg 1984; 34:331-338

(6.) Bach PB, Cramer LD, Warren JL, et al: Racial differences in the treatment of early- stage lung cancer. N Engl J Med 1999; 341:1198-1205

(7.) Greenwald HP, Polissar NL, Borgatt EF, et al: Social factors, treatment, and survival in early-stage non-small cell lung cancer. Am J Public Health 1998; 88:1681-1684

(8.) Polednak AP: Racial differences in the treatment of early-stage lung cancer. N Engl J Med 2000; 342:517-518

(9.) Van Rens MT, della Riviere AB, Elbers HR, et al: Prognostic assessment of 2,361 patients who underwent pulmonary resection for non-small cell lung cancer, stage I, II, and IIIA. Chest 2000; 117:374-379

(10.) Kaskowitz L, Graham MV, Emami B, et al: Radajation therapy alone for stage I non-small cell lung cancer. Int J Radiat Oncol Biol Phys 1993; 27:517-523

(11.) Graham MV, Purdy JA, Emami B, et al: Preliminary results of a prospective trial using three-dimensional radiotherapy. Int J Radiat Oncol Biol Phys 1995; 33:993-1000

(12.) Silby GS, Jamieson TA, Marks LB, et al: Radiotherapy alone for medically inoperable stage I non-small cell lung cancer: the Duke experience. Int J Radiat Oncol Biol Phys 1998; 40:149-154

(13.) Bush DA, Slater JD, Bonnet R, et al: Proton-beam radiotherapy for early stage lung cancer. Chest 1999; 116:1313-1319

(14.) Hayakawa K, Mitsuhashi N, Saito Y, et al: Limited field radiation for medically inoperable patients with peripheral stage I non-small cell lung cancer. Lung Cancer 1999; 26:137-142

(15.) McKenna RJ, Wolf RK, Brenner M, et al: Is lobectomy by video-assisted thoracic surgery an adequate cancer operation? Ann Thorac Surg 1998; 66:1903-1908

(16.) Kaga K, Park J, Nishiumi N, et al: Usefulness of video-assisted thoracic surgery (two windows method) in the treatment of lung cancer for elderly patients. J Cardiovasc Surg 1999; 40:721-723

(17.) Jaklitsch MT, Bueno R, Swanson SJ, et al: New surgical options for elderly lung cancer patients. Chest 1999; 116(6 suppl):480S-485S

(18.) Sugi K, Kaneda Y, Esato K: Video-assisted thoracoscopic lobectomy achieves a satisfactory long-term prognosis in patients with clinical stage IA lung cancer. World J Surg 2000; 24:27-30

(19.) McKenna RJ, Fischel RJ, Brenner M, et al: Combined operations for lung volume reduction surgery and lung cancer. Chest 1996; 110:885-888

(20.) DeMeester SR, Patterson GA, Saundareson RS, et al: Lobectomy combined with volume reduction for patients with lung cancer and advanced emphysema. J Thorac Cardiovasc Surg 1998; 115:681-688

(21.) Martel MK, Strawderman M, Hazuka MB, et al: Volume and dose parameters for survival of non-small cell lung cancer. Radiother Oncol 1997; 44:23-29.

(22.) Vanuytsel LJ, Vansteenkiste JF, Stroobant SG, et at: The impact of (18) F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) lymph node staging on radiation treatment volumes in patients with non-small cell lung cancer. Radiother Oncol 2000; 55:317-324

(23.) Choi N, Baumann M, Flentji M, et al: Predictive factors in radiotherapy for non-small cell lung cancer: present status. Lung Cancer 2001; 31:43-56

RELATED ARTICLE: KEY POINTS

* Less than one third of the patients with unresected early lung cancer have cancer-specific treatment.

* Patients who receive treatment have better outcome.

* All patients should be evaluated thoroughly for cancer-specific treatment, especially with recent advances in treatment modalities.

From the Department of Medicine, University of Arkansas for Medical Sciences, Little Rock.

Reprint requests to Abdul Rahman Jazieh, MD, MPH, University of Cincinnati Medical Center, Barrett Center for Cancer, 234 Goodman Ave, ML 0501, Cincinnati, OH 45267-0501.
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No portion of this article can be reproduced without the express written permission from the copyright holder.
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Author:Jazieh, Abdul R.
Publication:Southern Medical Journal
Geographic Code:1USA
Date:Oct 1, 2002
Words:2020
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