الفهرس 
Introduction & review of literatureOnly 14 pages are availabe for public view
 |  | from | 137 |  |  |
| | | from | 137 | | |
Abstract
Lung cancer is the most common cancer worldwide with estimated 1.8 million new cases diagnosed annually that accounted for 12.9% of newly diagnosed cancer. It is also the leading cause of cancer death worldwide with estimated 1.59 million death annually from lung cancer that account for 19.4% of total cancer death. Although major advances in diagnostic procedures more than half (57%) of patients diagnosed with lung cancer presented in advanced disease and nearly one half of patients with early stage lung cancer progress to metastatic disease within five years.
The present study aimed to construct a composite prognostic model integrating the anatomic extent of the tumor with clinical, functional, biochemical, histological and molecular factors in patients with advanced-stage non-small cell lung cancer treated with chemotherapy and targeted therapy and link it to overall survival rate.
This study was conducted in a retrospective design in collaboration with Division of Hematology and Oncology University of Alabama at Birmingham, USA on all patients with stage IV NSCLC who received chemotherapy or targeted therapy at Hematology/ Oncology Division University of Alabama at Birmingham from January 2002 to December 2012.
We collected the following data from medical records: patients data (age, gender and race); hagiological data (include histological subtypes, degree of differentiation and EGFR status); site of metastases, PET- CT data (site of max SUV and its value); smoking history (smoking status, smoking index and years of quit smoking); anthropometric measures (height, weight, calculated body mass index and body surface area), preexisting comorbidities and pretreatment laboratory data (pretreatment hemoglobin, total leucocyte count, platelets count, liver function test, kidney function test and electrolytes).
In our study patient’s age ranged from 25.3-88.9 with mean age of 61.97+ 11.1 and median age of 62.9. 232 patients <65 years (56.7% of total sample size) and 177 patients > 65 years old (43.3% of total sample size). There was no statistically significant difference in OS between patients whose age < 65 years compared to patients with age > 65 years (p=0.679) while there was statistically significant difference in PFS between the two age group for first line chemotherapy (p= 0.044).
Regarding patients gender, 230 patients were males (accounted for 56.2% of total sample) and 179 were females (account for 43.8% of total sample). There was statistically significant difference in OS between males and females in favor of female gender (p=0.02).
In our study, most of the patients were white accounting for 78.2% of study population followed by both African American and Asian who accounted for 19.3%. Regarding patients’ race there was no statistically significant difference in OS or PFS between white and African American (p=0.87, p=0.388 respectively).
Regarding histological characteristics of tumors most of patients in our study had adenocarcinoma (50.9%) followed by Non-small cell lung cancer not otherwise specified (28.6%) followed by squamous cell carcinoma (17.1%). There was no statistically significant difference in OS or PFS between different histological subtypes (p=0.42, 0.472 for OS and PFS respectively). Regarding degree of differentiation 55.3% of our patients had unknown tumor differentiation and reaming of our patients had poorly differentiated tumor which accounted for 26.4% of total studied population followed by moderately differentiated and well differentiated tumor. There was no statistically significant difference in OS or PFS between different degrees of histological differentiation (p=0.128, 0.472 for OS and PFS respectively).
Regarding pretreatment laboratory data, in our study there was statistically significant lower overall survival in the patients who had high total leucocytic count(p=0.006), high neutrophils count (p=0.033), high platelet count (p=0.002), low albumin level (p=0.001), high SGOT level (p=0.003), high SGPT level (p=0.001), high alkaline phosphatase (p=0.04), low sodium level (p<0.001), low chloride level (p=0.005), low magnesium level (p<0.001).
We tested factors that were statistically significant in univariate analysis using cox regression model. In our model factors that were significant using cox regression were presence of liver metastases (p=0.05), abdominal LN metastases (p=.031), (smoking status p=036), low albumin (p=.029), low sodium (p=017) and high SGPT (p=.009). As regard to PFS to first line treatment the factors that associated with lower PFS were age, poor performance status, present of liver and adrenal metastases and elevated liver enzyme.
For patients diagnosed on 2009 and later EGFR mutation was tested for every patient and we founded that 15.2 % were EGFR mutation positive while remaining patients were EGFR mutation negative or unknown (for patients treated before 2009)
In the present study as the first line treatment with tyrosine kinase inhibitors (TKI) for EGFR driven mutations were associated with best overall survival, with median survival of 19.11 months. This was followed by paclitaxel/Carboplatin/bevacizumab with median survival of 18.3, followed by pemetrexed containing regimens. This difference in overall survival was statistically significant (p = 0.012) in favor of tyrosine kinase inhibitors.
The addition of third line treatment was also associated with a statistically significant improvement in overall survival, with a median survival for patients receiving third line treatment of 26.1 vs 11.3 months (p<0.001) for patients not receiving third line treatment. The most common therapeutic regimens for third line treatment were single agent docetaxel, single agent pemetrexed, single agent gemcitabine, single agent vinorelbine, tyrosine kinase inhibitors or combined chemotherapy doublet, and there was no significant difference between all these regimens regarding overall survival. The addition of fourth and fifth line treatment also resulted in statistically significant improvements in overall survival with median survival compared to patients not receiving this treatment of 32.7 vs 13 months (p<0.001) and 40.3 vs 13.4 months (p=0.003) for patients received fourth and fifth line respectively.