Early-Stage Small-Cell Lung Cancer Research Articles

CT findings of early-stage small cell lung cancer in a low-dose CT screening programme

The survival of patients with small cell lung cancer (SCLC) is related to T, N, M components, and early diagnosis and treatment of limited stage SCLC may improve survival. The objective of this study was to review the initial and annual repeat screening computed tomography (CT) images of all five patients with SCLC, encountered in our 1996-1998 population-based screening for lung cancer, to clarify any subtle, characteristic CT findings of early-stage small cell lung cancer. The medical records of the patients were reviewed to examine demographic and clinical features. We identified characteristic CT features of SCLC in the lung periphery, which were related to gross pathologic findings with longitudinal spread along the bronchial wall: a small spindle-shaped or pyramidal lesion was found as a subtle CT finding of SCLC, and irregularly shaped nodular lesions (vermiform, pine-cone-like or tandem-like nodular lesions) appeared at a more advanced stage. Tumour volume doubling time of the cases ranged from 38 days to 217 days. All five patients were male smokers: four patients underwent surgery and adjuvant chemotherapy; three of them remain alive, while the remaining patient, an interval case, died of lung cancer. One patient refused treatment and died of a cause other than lung cancer. Annual repeat CT screening was useful for detecting SCLC cases mostly at a curable stage, and information about CT features, presented here, should help physicians identify SCLC at an earlier-stage and lead to a more successful treatment of the disease.

Surgery for Small Cell Lung Cancer.

Retrospective analyses have shown that, following surgical resection, patients with early-stage small cell lung cancer have a survival rate comparable to that seen with non-small cell lung cancer, especially if combined modality therapy is used. Surgery has been employed in three specific instances: primary surgery followed by postoperative chemotherapy and, when indicated, mediastinal irradiation for tumors presenting as peripheral nodules; multimodality therapy including induction chemotherapy followed by surgery; and radiotherapy in "resectable," very limited disease and "salvage surgery" for patients with limited disease previously treated, recurring at the primary site. The results of such surgery in very selected patients yields the best reported results in the treatment of small cell lung cancer. These approaches are worthy of further study.

The Role of Pulmonary Resection in Small Cell Lung Cancer

To analyze the outcome of surgical resection for patients with small cell lung cancer (SCLC). We identified all patients who underwent thoracotomy for SCLC at our institution from January 1985 to July 2002. All patients were staged using the American Joint Committee on Cancer TNM system. The median age of the 77 patients (44 men and 33 women) was 65 years (range, 35-85 years). Operations performed included thoracotomy with biopsy of hilar mass in 10 patients, wedge excision in 30 (6 with talc pleurodesis), segmentectomy in 4, lobectomy in 28, bilobectomy in 3, and pneumonectomy in 2. Mediastinal lymphadenectomy was performed in 50 patients and lymph node sampling in 19. Postoperative therapy Included chemotherapy alone in 20 patients, radiation therapy in 3, and combined chemotherapy and radiation therapy in 40. Median tumor diameter was 4 cm (range, 1.0-10.0 cm). Postsurgical tumor stage was IA in 7 patients, IB in 11, IIA in 8, IIB in 7, IIIA in 30, IIIB in 10, and IV in 4. A total of 19 patients (25%) had complications: atrial arrhythmia in 7 patients, pneumonia in 6, prolonged air leak in 3, and myocardial infarction, postoperative bleeding, and cerebrovascular accident in 1 each. Operative mortality was 3% (2/77). Follow-up ranged from 4 days to 170 months (median, 19 months). At last follow-up, 20 patients were alive. The estimated overall 5-year survival was 27% when excluding the 10 patients who underwent a biopsy without additional surgery. Five-year survival for stage I and II combined (n=33) was 38% compared with only 16% for stage III and IV combined (n=34) (P=.02). Overall median survival was 24 months; median survival for patients who underwent curative surgery was 25 months compared with 16 months for those who had a palliative procedure (P=.34). Pulmonary resection in patients with stage I or stage II SCLC is safe with low mortality and morbidity. Curative resection is associated with long-term survival in early stage SCLC in some patients and should be considered in selected patients.

Molecular Markers Help Characterize Neuroendocrine Lung Tumors

The terms large cell and mixed small-large cell neuroendocrine carcinoma (LCNC, MNC) have been proposed to describe distinct types of high-grade neuroendocrine lung tumors. However, cytologic appearance and neuroendocrine immunohistochemical stains cannot uniformly distinguish these from other neuroendocrine tumors, such as typical and atypical carcinoids or small cell carcinoma, or nonendocrine lung cancers such as large cell undifferentiated carcinoma. This study sought to determine the patterns of expression in LCNC and MNC of several molecular markers often abnormally expressed in lung cancers. Primary lung tumors with neuroendocrine features operated on between 1984 and 1994 were reviewed and classified as typical carcinoid (TC), atypical carcinoid (AC), LCNC, MNC, and small cell lung cancer (SCLC) based on mitotic rate, extent of necrosis, and cytoarchitectural features. Immunohistochemistry was performed using antibodies MIB-1 for Ki67, pAb1801 for p53, OP-66 for Rb, 31G7 for EGFR. Staining was scored as 0 to 4+ (0 = less than 5%, 1+ = 5% to 20%, 2+ = 20% to 50%, 3+ = 50% to 80%, 4+ = more than 80%) for p53, Ki67, and EGFR; and negative, focal, or positive for Rb. Overall survival was calculated by the Kaplan-Meier method and prognostic factors compared by log rank test. Ninety-two tumors were examined: 25 TC, 7 AC, 24 LCNC, 18 MNC, 18 SCLC. The LCNC and MNC presented more frequently as stage II or III tumors (n = 28, 66%) than TC and AC (n = 5, 15%). Median survival for LCNC and MNC was 18.7 months, for SCLC 14.3 months, and has not been reached for TC and AC tumors. TC and AC tumors were uniformly characterized by low proliferative rate, absent p53, and normal Rb staining. LCNC, MNC, and SCLC showed a high proliferative rate, abnormal p53, and absent Rb staining. Overexpression of EGFR was frequent in all five tumor types. (1) Ki67, p53, and Rb help distinguish LCNC and MNC from TC and AC. (2) Small numbers of patients preclude comparison of survival rates, but LCNC/MNC have a median survival similar to comparable early stage SCLC, and clearly worse than TC/AC. These results justify a sharp separation of high-grade neuroendocrine tumors from carcinoids, and suggest a close relationship between LCNC, MNC, and SCLC.

Surgery for small cell lung cancer

Retrospective analyses have shown that, following surgical resection, patients with early-stage small cell lung cancer have a survival rate comparable to that seen with non-small cell lung cancer, especially if combined modality therapy is used. Surgery has been employed in three specific instances: primary surgery followed by postoperative chemotherapy and, when indicated, mediastinal irradiation for tumors presenting as peripheral nodules; multimodality therapy including induction chemotherapy followed by surgery; and radiotherapy in “resectable”, very limited disease and “salvage surgery” for patients with limited disease previously treated, recurring at the primary site. The results of such surgery in very selected patients yields the best reported results in the treatment of small cell lung cancer. These approaches are worthy of further study.

Surgery and small cell lung cancer — an overview

The role of surgery in the management of small cell lung cancer (SCLC) is still controversial. Although approximately 30% of patients have limited disease at diagnosis, only l/3 of such patients will present with potentially totally resectable disease. Surgery like radiotherapy is a method of local control. In patients with limited disease treated by conventional methods of radiotherapy and chemotherapy, approximately 50% will ultimately recur in the loco-regional area, and 25% recur locally as the initial recurrence site. There is general agreement that neither surgery nor radiotherapy alone can effect 100% local control. Earlier reports of surgical treatment for small cell lung cancer were disappointing. Surgery alone rarely cured more than 10% of patients. With the advent of polychemotberapy and improved radiotherapy, surgery was abandoned as a treatment modality. However, more recently, it has been identified that there may be an improved loco-regional control rate utilizing surgery and chemotherapy with or without tboracic irradiation. Certainly, chemotherapy alone, even when complete responses are identified, cannot predictably sterilize the primary site. Added radiotherapy will control the primary site in only 50-75% of patients. In the past 10 years, there has been an explosion of retrospective analyses and phase II trials assessing surgery as a means of improved primary control and ultimate improved survival in early stage SCLC [l-19]. These reports can be subdivided into 2 broad categories. (1) primary surgery with post-operative chemoradiotherapy. (2) Neoadjuvant chemotherapy followed by surgery with or without thoracic irradiation. A third small group of patients have been treated by surgical resection as a salvage procedure once local recurrence as the only site has occurred. This review will focus on the experience of the Toronto Lung Oncology Group as well as attempting an analysis of other recently reported series.