• Users Online: 102
  • Home
  • Print this page
  • Email this page
Home About us Editorial board Ahead of print Current issue Search Archives Submit article Instructions Subscribe Contacts Login 


 
 Table of Contents  
ORIGINAL ARTICLE
Year : 2019  |  Volume : 10  |  Issue : 2  |  Page : 104-107

Primary Central Nervous System Lymphoma: An Experience of a Regional Cancer Center from India


1 Department of Radiotherapy and Oncology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
2 Department of Radiotherapy and Oncology, Maharishi Markandeshwar Institute of Medical Sciences and Research, Mullana, Ambala, Haryana, India

Date of Web Publication9-Sep-2019

Correspondence Address:
Dr. Rohit Mahajan
Department of Radiotherapy and Oncology, Maharishi Markandeshwar Institute of Medical Sciences and Research, Mullana, Ambala, Haryana
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jrcr.jrcr_15_19

Rights and Permissions
  Abstract 


Background: Primary central nervous system lymphoma (PCNSL) is a rare malignant non-Hodgkin's lymphoma and it accounts for 1% of all intracranial tumors. Only a few PCNSL studies have been reported from India, and hence, we conducted the retrospective study in our institute to analyze the main clinical features at diagnosis and the treatment results in PCNSL. Materials and Methods: We retrospectively reviewed the medical records of 32 patients with PCNSL who were treated from 2003 to 2014. A complete history was recorded, and the physical examination included neurological assessment. Baseline investigations such as complete blood count, blood biochemistry, chest X-ray, HIV serology, and two-dimensional echocardiography were also done. Contrast-enhanced computed tomography (CT) of the brain or magnetic resonance imaging, positron-emission tomography (if affordable), cerebrospinal fluid (CSF) analysis for cytology, histopathological diagnosis (following stereotactic or open biopsy), CT of the thorax and abdomen, and bone marrow biopsy were done. All patients received whole-brain radiotherapy (WBRT) (36–50 Gy) followed by cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) regimen for six cycles. Clinical features and the treatment results were analyzed. Results: A total of 32 patients with PCNSL were studied. The median age was 50 years (range: 32–70 years). Male: female ratio was 2.5:1. All the 32 patients were histologically diffuse large B-cell lymphoma. The most common presenting symptom was headache in 20 (62.5%) patients. The area of involvement was mainly cerebral hemispheres in 22 (68.8%) patients. Multifocal involvement was seen in 22 (68.8%) patients. CSF cytology was negative in all patients. All patients received WBRT (36–50 Gy) followed by CHOP regimen for six cycles. All patients were compliant to radiation as well as chemotherapy. On a median follow-up of 18 months, the median overall survival was 14 months (range: 1–80). Conclusions: Breaking the blood–brain barrier with radiotherapy followed by CHOP chemotherapy results in reasonable outcome in patients of PCNSL, especially in the Indian setting where general built and tolerance is low- to high-dose methotrexate regimens. Newer chemotherapy regimens or targeted therapies need to be evaluated to further improve the survival.

Keywords: Cyclophosphamide, doxorubicin, vincristine, and prednisone, India, primary central nervous system lymphoma


How to cite this article:
Yadav BS, Mahajan R, Sharma SC, Gupta A, Kumar S. Primary Central Nervous System Lymphoma: An Experience of a Regional Cancer Center from India. J Radiat Cancer Res 2019;10:104-7

How to cite this URL:
Yadav BS, Mahajan R, Sharma SC, Gupta A, Kumar S. Primary Central Nervous System Lymphoma: An Experience of a Regional Cancer Center from India. J Radiat Cancer Res [serial online] 2019 [cited 2019 Sep 15];10:104-7. Available from: http://www.journalrcr.org/text.asp?2019/10/2/104/266118




  Introduction Top


Primary central nervous system lymphoma (PCNSL) is a rare form of extranodal non-Hodgkin's lymphoma (NHL) which is confined to the brain, leptomeninges, eye, or spinal cord, without any evidence of lymphoma elsewhere in the body.[1],[2] PCNSL was a rare malignancy, constituting <1% of all intracranial tumors in the early 1970s. However, the incidence of PCNSL has steadily risen by more than ten-fold, from 2.5 cases/10 million population in 1973 to 30 cases/10 million in 1992 in the past 20 years.[3] By 1990, PCNSL formed nearly 4%–7% of all primary brain tumors.[4] The acquired immunodeficiency syndrome (AIDS) epidemic was the main factor responsible for the rising shift that began in the 1980s. However, the increase in the incidence of PCNSL was also seen in immunocompetent patients without AIDS over roughly the same period. This rising trend among immunocompetent individuals remains unexplained.[1],[5] Some later reports showed stabilization or in fact a slight decline in the incidence of PCNSL.[6] Few Indian studies also suggested that there has been no rise in the incidence of PCNSL.[2],[7],[8],[9] We conducted the retrospective study in our institute to analyze the main clinical features at diagnosis and the treatment results in PCNSL over a period of 11 years at our institute which is a referral cancer hospital.


  Materials and Methods Top


We retrospectively reviewed the medical records of 32 patients with PCNSL who were treated from 2003 to 2014. A complete history was recorded, and the physical examination included neurological assessment. Baseline investigations such as complete blood count, blood biochemistry, chest X-ray, and two-dimensional echocardiography were also done. HIV serology was done in all patients. Contrast-enhanced computed tomography (CT) of the brain or magnetic resonance imaging, positron-emission tomography (if affordable), cerebrospinal fluid (CSF) analysis for cytology, histopathological diagnosis (following stereotactic or open biopsy), CT of the thorax and abdomen, and bone marrow biopsy were done. All patients received whole–brain radiotherapy (WBRT) (36–50 Gy) followed by cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) regimen for six cycles. Clinical features and the treatment results were analyzed.


  Results Top


During the study period, there were 2423 intracranial neoplasms, of which 32 were PCNSLs, giving a percentage of 1.32%. A total of 32 patients with PCNSL were studied. The median age was 50 years (range: 32–70 years). Male: female ratio was 2.5:1 All patients were immunocompetent. The most common presenting symptom was headache in 20 (62.5%) patients. The area of involvement was mainly cerebral hemispheres in 22 (68.8%) patients. Multifocal involvement was seen in 22 (68.8%) patients. CSF cytology was negative in all patients [Table 1] and [Table 2].
Table 1: Clinical features

Click here to view
Table 2: Area of involvement

Click here to view


All the cases showed the features of NHL and were histologically classified as diffuse large B-cell lymphoma (DLBCL). All patients received WBRT (36–50 Gy) followed by CHOP regimen for six cycles. All patients were compliant to radiation as well as chemotherapy. Complete response (CR) was seen in 24 (75%) patients, partial response was observed in 4 (12.5%) patients, and 4 (12.5%) patients had progressive disease. Six patients relapsed out of 24 patients with CR. Disease recurred at the original site (n = 2), at a new site in the brain (n = 1), at the original and a new site (n = 1), and 2 patients had ocular relapse. Overall, 18 (56.25%) patients were disease free at a median follow-up of 18 months. On a median follow-up of 18 months, the median overall survival was 14 months (range: 1–80) [Table 3], [Table 4] and [Figure 1].
Table 3: Initial response

Click here to view
Table 4: Final disease status

Click here to view
Figure 1: Overall survival

Click here to view



  Discussion Top


The incidence of PCNSLs in India has been quite constant through the years, as suggested in previous as well as in the present study.[7],[8],[10] The median age of patients in our study was 50 years, which is almost the same as observed in other parts of India.[7],[8],[10] However, this a whole decade earlier than those reported in the West. This has been attributed to the demographic pattern of the Indian population.[8] In the present study, all patients were immunocompetent. A male preponderance was reported which is in line with other studies that have reported male preponderance among the immunocompetent population.[5],[7],[8],[11] All the patients were histologically diagnosed as DLBCL in our study. The treatment remains an important prognostic parameter in PCNSL of immunocompetent patients. Patients who received chemotherapy in combination with radiotherapy have a significantly better outcome when compared to cases who received radiotherapy or chemotherapy alone. The historical mainstay of therapy in PCNSL was previously WBRT alone.[12] Because of the limited long-term efficacy of WBRT alone, there has been considerable interest in combining chemotherapy with WBRT to improve response and survival. CHOP-based chemotherapies have been studied[13] but have not offered additional survival benefit to the radiation used alone, presumably because of the lack of penetration to the CNS. Subsequently, research has been on the role of systemic methotrexate at doses known to penetrate into the CNS preceding WBRT in PCNSL. The results with high-dose methotrexate have shown better overall survival when combined with radiotherapy but at the cost of higher toxicity.[14],[15] In developing countries like ours, a good number of patients cannot tolerate high-dose methotrexate because of poor general condition and financial constraints. High myelosuppression and severe neurological toxicity is present with high-dose methotrexate which needs intensive care in high dependency unit (HDU), availability of which is a question mark in our resource constraint country. Thus, WBRT, which takes care of the local disease and breaking blood–brain barrier (BBB) followed by systemic CHOP-based chemotherapy, seems to be a viable option where general condition and affordability of the patients are poor for HDU setting.


  Conclusions Top


Our study shows that there has been no significant rise in the incidence of PCNSL over the past 13 years, which is in line with the findings of previous studies from India.[2],[7],[8],[10] PCNSL is most commonly seen in the middle-aged, and DLBCL is the most common histological pattern. Unlike the West, the association of PCNSL with HIV/AIDS in India is very low despite the high prevalence of HIV/AIDS cases. Breaking the BBB with radiotherapy followed by CHOP chemotherapy results in reasonable outcome in patients of PCNSL, especially in the Indian setting where general built and tolerance are low- to high-dose methotrexate regimens.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Rubenstein JL, Treseler P, O'Brien JM. Pathology and genetics of primary central nervous system and intraocular lymphoma. Hematol Oncol Clin North Am 2005;19:705-17, 7.  Back to cited text no. 1
    
2.
Paul T, Challa S, Tandon A, Panigrahi M, Purohit A. Primary central nervous system lymphomas: Indian experience, and review of literature. Indian J Cancer 2008;45:112-8.  Back to cited text no. 2
[PUBMED]  [Full text]  
3.
Corn BW, Marcus SM, Topham A, Hauck W, Curran WJ Jr. Will primary central nervous system lymphoma be the most frequent brain tumor diagnosed in the year 2000? Cancer 1997;79:2409-13.  Back to cited text no. 3
    
4.
Miller DC, Hochberg FH, Harris NL, Gruber ML, Louis DN, Cohen H, Pathology with clinical correlations of primary central nervous system non-Hodgkin's lymphoma. The Massachusetts general hospital experience 1958-1989. Cancer 1994;74:1383-97.  Back to cited text no. 4
    
5.
Fine HA, Mayer RJ. Primary central nervous system lymphoma. Ann Intern Med 1993;119:1093-104.  Back to cited text no. 5
    
6.
Kadan-Lottick NS, Skluzacek MC, Gurney JG. Decreasing incidence rates of primary central nervous system lymphoma. Cancer 2002;95:193-202.  Back to cited text no. 6
    
7.
Powari M, Radotra B, Das A, Banerjee AK. A study of primary central nervous system lymphoma in Northern India. Surg Neurol 2002;57:113-6.  Back to cited text no. 7
    
8.
Sarkar C, Sharma MC, Deb P, Singh R, Santosh V, Shankar SK. Primary central nervous system lymphoma – A hospital based study of incidence and clinicopathological features from India (1980-2003). J Neurooncol 2005;71:199-204.  Back to cited text no. 8
    
9.
Agarwal PA, Menon S, Smruti BK, Singhal BS. Primary central nervous system lymphoma: A profile of 26 cases from western India. Neurol India 2009;57:756-63.  Back to cited text no. 9
[PUBMED]  [Full text]  
10.
Pasricha S, Gupta A, Gawande J, Trivedi P, Patel D. Primary central nervous system lymphoma: A study of clinicopathological features and trend in western India. Indian J Cancer 2011;48:199-203.  Back to cited text no. 10
[PUBMED]  [Full text]  
11.
Basso U, Brandes AA. Diagnostic advances and new trends for the treatment of primary central nervous system lymphoma. Eur J Cancer 2002;38:1298-312.  Back to cited text no. 11
    
12.
Nelson DF, Martz KL, Bonner H, Nelson JS, Newall J, Kerman HD, et al. Non-Hodgkin's lymphoma of the brain: Can high dose, large volume radiation therapy improve survival? Report on a prospective trial by the radiation therapy oncology group (RTOG): RTOG 8315. Int J Radiat Oncol Biol Phys 1992;23:9-17.  Back to cited text no. 12
    
13.
Mead GM, Bleehen NM, Gregor A, Bullimore J, Shirley D, Rampling RP, et al. Amedical research council randomized trial in patients with primary cerebral non-Hodgkin lymphoma: Cerebral radiotherapy with and without cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy. Cancer 2000;89:1359-70.  Back to cited text no. 13
    
14.
DeAngelis LM, Seiferheld W, Schold SC, Fisher B, Schultz CJ; Radiation Therapy Oncology Group Study 93-10. Combination chemotherapy and radiotherapy for primary central nervous system lymphoma: Radiation therapy oncology group study 93-10. J Clin Oncol 2002;20:4643-8.  Back to cited text no. 14
    
15.
Rudresha AH, Chaudhuri T, Lakshmaiah KC, Babu G, Lokesh KN, Rajeev LK, Primary central nervous system lymphoma in immunocompetent patients: A regional cancer center experience. South Asian J Cancer 2017;6:165-8.  Back to cited text no. 15
    


    Figures

  [Figure 1]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
Abstract
Introduction
Materials and Me...
Results
Discussion
Conclusions
References
Article Figures
Article Tables

 Article Access Statistics
    Viewed54    
    Printed0    
    Emailed0    
    PDF Downloaded14    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]