Background
Lymphomas are ranked as the fifth most common cancer in Lebanon as suggested by several epidemiological studies done at the time [
1,
2]. Non Hodgkin Lymphoma (NHL) patients constitute a group of interest to many epidemiologists [
1]. In contrast to the adequate information available on the epidemiology of NHL from developed nations, such data from developing countries is scattered [
3]. To date, there is concern about the need of information regarding the prevalence of lymphoid neoplasm subtypes in the Lebanese population [
1]. Worldwide, the incidence of NHL is rising, mostly in older population. This is also the case in Lebanon [
2,
4].
NHLs consist of a diverse group of hematologic malignancies deriving from mature or immature lymphocytes (B, T or NK). B-cell lymphomas (BCLs) account for 80 to 85% of the cases especially in the Western world and United States (US), and T-cell lymphomas (TCLs) accounts for the rest (15 to 20%) [
5]. In Lebanon, most NHL cases are of B-cell origin [
1]; however, histologic subtypes can vary in different parts of the world [
6]. The subclassification of the disease underwent significant changes due to improvements in the molecular biology and cellular genetics field especially with the introduction of anti-CD 20 antibody that has supplemented the diagnosis and treatment options available for BCL [
7]. Obviously, advances in treatment modalities contributed to improvement in survival for several NHL subtypes. Besides patients characteristics, socioeconomic factors influence survival because it is documented that in countries with higher income, the 5 year overall survival (OS) is almost 80% and much lower in middle or low income setting, with respect of the difference in age and histology [
8].
NHL is the most prevalent hematopoietic neoplasm ranking seventh in frequency among all cancers [
9]. Diffuse large B cell lymphoma (DLBCL) type constitutes 40% of lymphomas, and is more diagnosed among middle-aged men, while follicular lymphoma (FL) accounts for about 20%. These subtypes are most frequent in North America and Europe [
8]. The NHL subtypes variation in each country appears to be related to population characteristics and environmental factors. For example, the incidence in the US is greater than other countries with a predominant nodal disease. Although NHL incidence is relatively low in Asian countries, Asians generally present with a higher proportion of TCLs [
8]. In Africa, there is insufficient data available but the most documented type is Burkitt’s lymphoma [
10]. As for the Arab countries, NHL is common in Egypt, Kuwait, Oman, and Saudi Arabia, accounting for about 10% of all cancers [
10]. It is the fourth major cause of cancer incidence in Egypt, Oman, Qatar and Bahrain [
11].
The purpose of this study was to evaluate and recognize the most prevalent subtypes of NHL in Lebanon. Because there is scarce multi centric data demonstrating the epidemiological patterns of NHL occurrence in Lebanon and knowing that there is unpublished data and only a small percentage of all newly Lebanese cancer cases are diagnosed in tertiary hospitals, there is constant need of studies and timely documentations of the disease prevalence. This may serve as an added value to the current literature and a basis for future studies. Hence, we decided to conduct such study at our centers and evaluate the clinical features of NHL hypothesized to parallel those seen in Western countries.
Discussion
NHL encompasses various lymphoid neoplasms with different clinical and biological profiles. As evidenced in our study, NHL is commonly observed among middle-aged males with B-cell type representing more than two third of the cases. DLBCL and FL were the predominant subtypes. Patients in this study mainly presented at an advanced stage thus suggesting the probable effect of poor access to medical care.
NHL disease among Lebanese patients appear to be more prevalent in adult males, a tendency also seen in the western countries [
12]. According to the literature, males are more affected of NHL than females with approximately 30% higher incidence [
15]. In fact, several researchers investigated how sex hormones modulate lymphoid neoplasms. The reduced rate of NHL among females is best explained by the effect of estrogen on modulating tumoral cell proliferation [
16]. In their study, Yakimchuk et al. investigated the anti-proliferative effect of estrogen through estrogen receptor β (ERβ) signaling [
17]. Furthermore, in a study done in 2016 by Perry and colleagues evaluating the frequencies of NHL subtypes in five developing regions of the world, there was a significant difference in the sex distribution with a notably higher number of males in contrast to the developed world [
18]. This could suggest the presence of sex inequality when seeking medical care in these countries and consequently women being underdiagnosed with lymphomas [
19]. Our results were in accordance with previous studies stating the predominance of NHL in males. Further studies stratifying patients according to their socioeconomic status are warranted to assess whether this factor impact access to healthcare in our country.
In this study, the mean age of the patients is 53.52 years, which is moderately higher than that of patients from Arab countries: Saudi Arabia (46 years) (Koriech and Al-Kuhaymi, 1994) [
20], Jordan (44 years) from 1996 till 1999 (Almasri et al., 2003) [
21] and Egypt (51.6 years) from 1995 to 2004 (Abdel-Fattah et al., 2007) [
22]. In northern India the mean age was 47 years (Sandhu et al., 2018) [
4] from 1997 to 2000. In the US, between 2012 and 2016, the mean age at diagnosis of NHL was 67 years [
8]. In South East Asia, from 2007 to 2014 the mean age was 56 years (Intragumtornchai et al., 2018) [
23].
B-cell type represented 86.3% of NHL cases in Lebanon, which is in accordance with the worldwide reported rates (80–90%), except for the Eastern countries where T-cell type rate is higher [
7]. The proportion of TCL is 13.7% of all cases in our study. This is comparable to the results in western countries where TCL proportion does not exceed 10% in England [
24], 12% in France (Troussard et al., 2009) [
25] and 15% in the US [
26]. However, this percentage of TCL is very low when compared to China (30% of all NHL) (Yang et al., 2011) [
27] and Japan (27%) (Aoki et al., 2008) [
28]. Regarding the higher frequency of TCLs in Asia than the rest of the world, this appears to be related to the HTLV-1 virus infection which is more prevalent in Japan and the Caribbean countries [
7]. In addition when stratifying according to gender, the observed proportion of TCLs among male cases was 65.1% (vs. 34.9% among females). This is in accordance with results from the Surveillance, Epidemiology, and End Results (SEER) where the reported incidence of TCLs showed a higher male/female ratio from 1992 to 2001 in contrast to other subtypes [
18].
In Lebanon, a one-year national study of 227 cases of lymphomas classified according to the 2001 WHO classification of malignant lymphomas has been published by Otrock et al. in 2013. The results were notable for 88% of BCLs and 9% of TCLs. These proportions are in part similar to the observed results in our study [
29].
High-grade tumor predominated in 80.1% of cases, with DLBCL and FL being the most common subtypes. DLBCL comprises 54% of all cases. Similar frequency was noted in Jordan (53%) [
23] and Algeria (52.8%) (Boudjerra et al., 2015) [
30]. FL represents 17.2% of the cases, in comparison to 15.9% in the UK (Smith et al., 2015) [
31] and 17% in the US (Chihara et al., 2014) [
32] while a rate of 7% was noted in Saudi Arabia (Akhtar et al., 2009) [
33]. SLL comprised less than 2% of NHL cases in contrast to 15% in the USA [
16]. MCL represents 3% of all BCL, which is close to the rate seen in Saudi Arabia (2%) (Akhtar et al., 2009) , USA (3%) (Wu et al., 2009) [
34] and France (4%) (Troussard et al., 2009) [
27].
Most of the patients in this study presented at an advanced stage, with stage 4 presentation being 33.1%. This is in part in accordance with the SEER reported results with 34% of patients presenting at stage 4 [
8]. Similar results were described in Saudi Arabia [
22]. Advanced stage (III/IV) occurring at 58.3%, is more frequent in our population than in the west, this may suggest late diagnosis related to poor socioeconomic status preventing access to healthcare.
Extranodal presentation was described in more than one-third of the patients (36.5%). Extranodal disease at diagnosis was documented in 20–30% of patients in the US (Ries et al., 2005) , and in more than 65% in patients from Saudi Arabia [
22]. This disease is documented mostly in patients from France and Kuwait with 42 and 52% incidence rate respectively [
22].
In this study, 18.3% (128) of patients received RT. When comparing the variables by age (≤64 vs ≥65 years), the results showed that a significantly lower percentage of patients who received RT was aged 65 years or more. In general, the indication of RT has been limited progressively to a complementary RT after chemotherapy especially in aggressive localized diseases, and this has been facilitated after the emergence of positron emission tomography (PET) scan imaging that helps selecting patients who are candidates for this approach [
35]. Current evidence shows that in indolent NHL, RT may be curative in early stage disease and palliative in more advanced diseases. In aggressive NHL, RT is used to cure stage I disease after short course chemotherapy and may be given to consolidate chemotherapy response in bulky or extranodal sites. It has a valuable palliative role for aggressive lymphoma causing local symptoms in patients intolerant to chemotherapy [
36]. In an attempt to review the literature where the importance of radiation therapy was assessed, several studies showed different results. In 1998, Miller et al. had investigated the superiority of three cycles of CHOP followed by involved-field radiotherapy (IFRT) to eight cycles of CHOP alone in the setting of NHL. They concluded that RT is efficacious in the setting of limited diseases and can provide curative outcomes, thus advocating its application among patients with localized lymphomas [
37]. Connors et al. have also suggested that consolidative RT is an advantageous treatment and leads to decreasing the chemotherapy dose, well needed in the case of elderly patients [
38]. Overall, the place of RT in the standard care of DLBCL appears debatable because some studies favors its use and others do not show definite advantage [
39]. In this study, information about the bulky tumor status (defined as any mass greater than 5 cm), standardized uptake values (SUVs) on PET CT and the choice of chemotherapy before radiation in these patients are lacking. Further studies are needed to determine the characteristics of patients that had benefit from RT.
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