Treatment Outcome in Patients with Metastatic Non-Small Cell Lung Cancer at Presentation (Retrospective Study)

INTRODUCTION

Worldwide, lung cancer occurred in approximately 1.8 million patients in 2012 representing 13% of all new cancer cases) and caused an estimated 1.6 million deaths, lung cancer has the highest mortality rate worldwide .⁶ In the United States, there will be approximately 234,000 new cases of lung cancer and over 154,000 deaths annually.¹⁸

In Egypt ,The lung cancer incidence is about 4.6% of all cancers in both sexes, representing about 6.9% of male cancers (5017 cases) and 2.5% of female cancers (3634 cases) and mortality rate 6.8% in males and 3.8% in females (Globocan fact sheet, Egypt 2012).Lung cancer deaths in Egypt reached 4,429 per 100,000 of population in 2002 .³

Platinum-based chemotherapy remains the standard-of-care for most patients affected by advanced non small cell lung cancer (NSCLC) , Recent evidence emphasized that the optimal number of first-line platinum cycles should be four for any NSCLC histology.³

After the era of advances in the molecular biology, many mutations had been discovered in lung cancers

cells, these mutations are currently drive the choice of first line treatment targeted therapy in such patients after the statistical significant survival and clinical benefits with high acceptable toxicity profile that had observed with the use of this class of therapy when compared with chemotherapy as first line treatment¹⁷

Recently, the use of immune therapy in the first line treatment either alone or in combination with chemotherapy in selected patients with PDL-1 expression showed a significant superior progression-free survival (PFS) and OS when compared with standard chemotherapy alone. Therefore, the Key-note 024 trial was prematurely stopped in order to allow patients receiving chemotherapy to cross over to the immunotherapy arm.¹³

The primary objective of this study is to assess the outcome of treatment in patients who presented with metastatic non-small cell lung cancer in term of response to treatment, treatment related toxicity, progression free survival and overall survival.

PATIENT AND METHODS

This Retrospective study included 56 patients with metastatic non-small cell lung cancer who received systemic treatment at our department during the period between June 1st 2012 and June 1st 2017, and meet the following inclusion criteria; histopathology confirming non-small cell lung cancer either histologically or cytological, age younger than 80 years old, Performance status 0-3 (WHO) and radiological confirmed distant metastases at presentation.

Charts of included patients have been retrieved from the archive to collect the following data: Age, sex, special habits (eg. smoking), comorbidity, performance status, histopathology, chemotherapy related details, radiotherapy if received, and finally response to treatment according to RECIST criteria.

Overall survival interval was considered as the period between the date of histological diagnosis and the date of the last follow-up (for censored observations) or the date of death (for uncensored observations), while progression free interval was considered  as the period between date of the first treatment and the date of the last follow-up (for censored observations), or date of death or disease progression whichever happen first (for uncensored observations).

Statistical methods:

Data were coded and entered using the statistical package SPSS version 23. Data was summarized using mean, standard deviation, median, minimum and maximum for quantitative variables and frequencies (number of cases) and relative frequencies (percentages) for categorical variables. One-sided log-rank of Kaplan—Meier survival estimates was used for statistical analysis of overall survival and progression free survival, while the unpaired T test and one-way ANOVA test were used in the univariate analysis of the variables. Results of P-values less than 0.05 were considered as statistically significant.

Ethical approval:

The current investigation was had been executed based on the recommendations approved by the ethical committee, Faculty of Medicine, Al-Azhar University, Cairo, Egypt, before the start of this study.

RESULTS

In the study group, the mean age of the 56 included patients was 57.9 (±10.3),  male patients were 44 (78.6 %) , and females were 12   (21.4 %),  with male to female ratio 3.5 : 1  respectively; 40 patients (71.4 %)  were smokers and 16 patients  (28.6 %) weren’t  smokers; performance status (PS) at presentation  was reported 0 for 23 patients (41.1 %), PS I for 18 patients (32.1 %),   PS II for 12 patients (21.4 %) and   PS III for three patients (5.4 %) 

     All patients had NSCLC with different subtypes: 35 patients (62.5%) had  adenocarcinoma, nine patients (16.07 %) had squamous cell carcinoma, seven patients (12.5 %) had undifferentiated carcinoma, four patients (7.14%) hadlarge cell carcinoma and one patient only (1.78 %) had spindle cell (sarcomatoid); as regard  pathological  grading,  30 Patients  (54.5 %) had grade II  and  26  patients (45.5 %) had grade 3 tumors;  the most common site of metastasis was bone  in 21 patients  (37.5 %) followed by contralateral  lung or pleural metastasis in 18  patients (32.1 %),  suprarenal metastasis in 14 patients (25.0 %), brain metastasis in 13 patients (23.2 %)  and liver metastasis 6 patients (10.7  %). Table (1)

Active treatment was delivered for 43 patients (76.8%)  while 13 patients (23.2%) didn’t receive active treatment; 29 patients (51.7 %) received  chemotherapy with a median number of four cycles (range 1-9); 21 patients (37.5 %) received Gemcitabine + cisplatin,  five patients (8.9 %) received   carboplatin + etoposide, tow patients (3.6 %) received paclitaxel + cisplatin and one patient (1.7  %) received  carboplatin + paclitaxel; while 37 patients  (65.9 %) received palliative radiotherapy of them 14 patients (25 %) missed after end of treatment. On the other hand six patients (10.7 %) missed after first visit, seven patients (12.5 %) managed with best supportive care.

Only 7 patients (12.5 %) was able to receive second line  chemotherapy: six of them (10.7 %) received  taxenes based regimen (paclitaxel  or  docetaxel) and only one patient (1.7 %) received  (cisplatin + navelbine).

The most common toxicities  showed with chemotherapy :grade 2 – 3 Anemia in  15 patients  (51 %)  who treated with (cisplatin \gemcitabine)  or (carboplatin \ gemcitabine)  regimens , G2-3  Nausea and vomiting developed in 14 patients (48.2 %) who received  platinum  based  chemotherapy , however some patients developed another toxicity profiles either related to chemotherapy or radiotherapy  but it was insignificant as showed in table ( 2 )

According to RECIST criteria v1.1 response to 1st line chemotherapy was reported in patients charts as following; 11  patients  (19.6 %) had partial response,  four patients (7.1 %) had stationary disease and 11 patients ( 19.6 % ) developed  disease progression, while no assessment was reported in the charts of  three patients (5.35%). table (3): 

Table 1:  Patients and disease criteria

Table 2:  Treatment received and toxicity profile

Table 3:  Response to treatment

The median progression free survival was 8.9 months for all patients included in this study, however it was 9.3 and 7.5 months for patients who received chemotherapy and didn’t receive any treatment respectively, with no statistical difference between the two group (P= 0.3). Figure (1)

Fig. 1: Median Progression free survival (PFS) curve

Median overall survival (MOS) was 10.8 months, at subgroup analysis  systemic treatment showed significant improving in overall survival as following : in patients who didn’t receive treatment MOS 10.8 but in patients who received chemotherapy MOS was 13.6 (9.3-17.9) ( P= 0.019). Figure (2)

Fig. 2: median  overall survival (MOS) curve

On the other hand PFS and OS did not significantly affected by any of the following factors; age, sex, PS, special habits, histopathological subtype, pathological  grade , site of metastasis, type of chemotherapy or number of cycles.……………………………………………………………………