THE ROLE OF SURGERY IN SMALL CELL LUNG CANCER

Bashir Ahmad Bhat 1 , Mushtaq Ahmad 1 , GhNabi Lone 2 and ShiekhAejaz Aziz 3 . 1. Department of surgery, Sher-I-kashmir Institute of of Medical Science (SKIMS),Srinagar, Jammu and Kashmir, India-190011. 2. Department of CVTS, Sher-I-kashmir Institute of of Medical Science (SKIMS),Srinagar, Jammu and Kashmir, India-190011. 3. Department of Medical Oncology, Sher-I-kashmir Institute of of Medical Science (SKIMS),Srinagar, Jammu and Kashmir, India-190011. ...................................................................................................................... Manuscript Info Abstract ......................... ........................................................................ Manuscript History


ISSN: 2320-5407
Int. J. Adv. Res. 5 (11), 426-431 427 continue to rise because aggressive tobacco industry marketing is leading to a growing prevalence of cigarette smoking. This is also one of the major causes of cancer deaths in our valley. Lung cancer has been found to be the second commonest cancer according to a hospital-based data from Kashmir. The crude incidence rate, age standardized (world), and truncated age adjusted (40-69 years, world) incidence rates for lung cancer per 100 000 population are 4.01, 6.48 and 15.28 respectively (Males 6.55, 10.09 and 23.94 respectively and females 1.19, 2.14 and 4.65) 1 .
Small cell lung cancer (SCLC) accounts for approximately 15% of new cases of lung cancer diagnosed annually and for up to 25% of lung cancer deaths each year 2 . However, the overall incidence and mortality rates of SCLC in the United States have decreased during the past few decades 2,3 . Possible causes for this trend include the decrease in smoking prevalence especially in white men and a change to low-tar filters 3 . Recent evidence suggests that women of all ages are more likely to present with SCLC than men, and that younger women are more likely to present with SCLC than older women. Women who begin smoking at an early age are more susceptible to SCLC 4-6 .

Material and Methods:-
The study was conducted in the departments of CVTS and Medical oncology SKIMS Soura from May-2008 to Sep-2010. The study was prospective /retrospective in design. All the patients who underwent pulmonary resection for LD-SCLC from Jan-2000 to Sep-2010 were included in the study. In all patients diagnosis was established by histologic examination of resected specimen. Some patients did not have a confirmed diagnosis of SCLC before resection and were taken to surgery for peripheral solitary pulmonary nodules suspected of being cancerous. All the patients whose pre operative diagnosis was known underwent a complete staging procedure. This included, a detailed history and physical examination, the evaluation of the performance status according to Karnofsky, a complete blood count and biochemical profile, cardiac and pulmonary function tests, chest X-ray, bronchoscopy, computed tomography of chest, the upper abdomen and brain, abdominal ultrasonography, and bone scan. Patients were classified using the TNM staging system according to the criteria established by the American Joint Committee for Cancer Staging. Operative mortality was defined as death within 30 days of operation or during same hospitalisation. The time of surgery was used as the starting date. Survival was defined as the interval between date of surgery and date of death or last follow-up. Patients who died in the perioperative period were not considered in the survival analysis. Survival for all patients was recorded upto Sep-30, 2010.

Observations:-
The study group consisted of 30 patients (27 men and 3 women). The median age was 56 (range, 35-80 years). There were 27 males and 3female, male to female ratio was 9:1. Twenty eight patients were active smokers or had a history of smoking at the time of diagnosis; the remaining two patients were non-smokers. All the patients included in our study were symptomatic. Cough was the most common presenting symptom (30%), followed by dyspnea (20%), chest pain (20%) and weight loss (10%). All patients were classified using the TNM staging system according to the criteria established by the American Joint Committee for Cancer Staging. Most of the patients had stage I disease ; 18 patients(60%), IA(n=9), IB(n=9), stage II; 6 patients(20%), IIA(n=3), IIB(n=3), stage III; 6 patients(20%), IIIA(n=6). Lobectomy was carried out in 21 patients (70%), patients. Bilobectomy in 3 patients (10%), and pneumonectomy in 6 patients (20%). The pathologic subtype was pure small cell lung carcinoma in 21(70%) of patients, small and large cell neuroendocrine carcinoma (LCNEC) in 3 (10%) of patients and small cell in combination with other tumor type in the remaining 6(20%) cases. Post surgical pathological staging was done using the TNM staging system according to the criteria established by the American Joint Committee for Cancer Staging. Most of the patients were in stage I (40%), stage II (40%), and in stage III (20%) patients. A total of 6 patients (20%) had complications, which included supraventricular arrhythmia in 3 patients, pneumonia, prolonged air leak and wound infection in 1 each. There was only one postoperative death that of a patient with a pulmonary embolism at post operative day 13, giving a 30-day surgical mortality of 3.3%. Postoperative therapy included chemotherapy in 8 patients, radiotherapy in 6, chemo-radiotherapy in 10, PCI in 7 patients and 6 patients received no adjuvant therapy including one patient who died in immediate post-op period. The follow up ranged from 6 weeks to 68 weeks, mean follow up was 36.52 months (SD 25.69). One year survival was better for female patients, it was 59.3% and 100% for males and females respectively (p= .165).Five year survival for females was better than that of males. For females it was 66.7% and 33.3% for males. Patients who underwent lobectomy had a 5 year survival of 42.9%, bilobectomy patients had a 5 year survival of 33.3% and in pneumonectomy patients 5 year survival was 16 7%. Patients who underwent lobectomy had a 5 year survival of 42.9%, bilobectomy patients had a 5 year survival of 33.3% and in pneumonectomy patients 5 year survival was 16 7%. Patients who received chemoradiotherapy after surgery had a 5 year survival of 40%, patients receiving chemotherapy had a survival of 62.5%, 428 and in patients receiving no adjuvant therapy, none of the patient survived for more than 2 years. 5 year survival for post surgical stage I was 58.3%, stage II was 25.0% and for stage III 16.7%. A total of 6 patients had relapse, 3 patients had local relapse and 3 patients had a relapse at distant site.

Discussion:-
The most frequent localized relapse is at the site of the tumor. Even with the addition of thoracic radiation, relapse continues to occur at the primary site in up to one third of patients. 7 This suggests that if survival is to improve, more aggressive local tumor control is necessary. This has led to renewed interest in the role of surgical resection of the primary tumor and regional lymph nodes.
In our study the incidence of lung cancer (SCLC) increased with increasing age. Majority of the patients (80%) were seen in the age group 46-75 years with maximum 40% patients in age group 56-65 years. The median age was 56 years (range, 35-80 years). These observations were in accordance with the literature available. Federico Rea et al 8 reported the median age of 57 years (range, 30-75 years) in their series.
In our patients overwhelming majority (90%) were males as compared to only 10% females. The present study has revealed that mainly the males were affected with a male to female ratio of 9/1 which was higher than the previous studies in western countries, but was consistent with that of the developing countries, that either lack regulations or are far less strict in regulating nicotine and tar content of cigarettes and also in which the average tar yield is higher than western countries 3 . This observation was contrary to most of the western literature where the incidence of SCLC among females is also on the rise due to increase in smoking 4-6 . Similar observations were made by HasanTatlisozet al 9 the study group consisted of 141 male and 14 female patients, with a male to female ratio of 10:1.
In our study histopathologic profile of patients revealed 70% of patients with histopathology of pure small cell carcinoma, 10% small cell carcinoma and large cell neuroendocrine carcinoma (LCNEC), small cell and other combinations in 20%. These findings were consistent with other studies. Lim E et al 10 reported that pure small cell carcinoma was present in 73% of patients whilst combined small cell carcinoma was present in 27% patients.
All operations were elective. Most of patients underwent lobectomy (n=21, 70%), because that was the preferred operation if the lesion was completely resectable, the general medical condition of the patient was acceptable, and respiratory mechanics and gas exchange were satisfactory. In 3 patients (10%) a bilobectomy was performed and in 6 patients (20%) a pneumonectomy was necessary due to centrally located tumors or tumors crossing the interlobar fissure affecting more than one lobe. These observations were consistent with literature. Shepherd et al 11 reported 15 patients (19.4%) had a pneuomonectomy, 46 had a lobectomy (60%), and 2 had wedge resections. Post surgical stage was IA (n=6), IB (n=6), IIA (n=3), IIB (n=9), IIIA (n=6).
There was one postoperative death, that of a patient with a pulmonary embolus at 13 postoperative day, giving a 30day surgical mortality of 3.3%. These findings were in accordance with other studies. Vidhan Chandra et al 13 reported a operative mortality of 3% (2/77) in their study.
Postoperative complications occurred in 20% of the patients (6/30). There were 6 nonfatal complications, all involving the cardiorespiratory system, including 3 cases of supraventicular arrhythmia, 1 case of pneumonia, 1 case of prolonged air leakage and 1 case of wound site infection. These observations were consistent with other studies. A. Granetzny et al 12 reported a postoperative complication rate of 17% (16/95) which comprised of 6 cases of atrial fibrillation, 5 cases of atelectasis, 3 cases of pneumonia and 2 cases of wound infection. Adjuvant treatment was recorded as radiotherapy, chemotherapy, or both as appropriate. Although all patients were referred for consideration of adjuvant therapy 5 patients did not receive any additional postoperative treatment. Of the 5 patients who underwent surgery alone, 3 refused any adjuvant therapy and 2 died before completion of chemotherapy recommended by the medical oncologist. 8 patients received chemotherapy, 6 patients received radiotherapy, 10 patients received combined chemo-radiotherapy, and 7 patients received prophylactic cranial irradiation (PCI), including 2 patients with stage-I disease.  Another subgroup with good long-term survival was a group of 8 patients who received postoperative adjuvant chemotherapy, with overall 1-, and 5-year survivals of 82% and 62.2% respectively. Considering the subgroup of 5 patients who received no adjuvant therapy (surgery only), all died within two years of surgery. These results achieved statistical significance (p=0.001).