|Year : 2015 | Volume
| Issue : 4 | Page : 541-544
Retrospective audit of clinico-pathologic features and treatment outcomes in a cohort of elderly non-Hodgkin's lymphoma patients in a tertiary cancer center
CK Nair1, VM Patil1, V Raghavan1, S Babu2, S Nayanar3
1 Department of Clinical Hematology and Medical Oncology, Malabar Cancer Centre, Thalassery, Kannur, Kerala, India
2 Department of Imageology, Malabar Cancer Centre, Thalassery, Kannur, Kerala, India
3 Department of Oncopathology, Malabar Cancer Centre, Thalassery, Kannur, Kerala, India
|Date of Web Publication||10-Mar-2016|
C K Nair
Department of Clinical Hematology and Medical Oncology, Malabar Cancer Centre, Thalassery, Kannur, Kerala
Source of Support: None, Conflict of Interest: None
INTRODUCTION: There is limited data from India regarding elderly non-Hodgkin's lymphomas (NHL) patients. Hence, this audit was planned to study the clinic-pathological features and treatment outcomes in elderly NHL patients. METHODS: Retrospective analysis of all NHL patients above age of 59 years treated at the author's institute, between December 2010 and December 2013 was done. Case records were reviewed for baseline details, staging details, prognostic factors, treatment delivered, response, toxicity and efficacy. SPSS version 16 (IBM, Newyork) was used for analysis. Descriptive statistics was performed. Kaplan–Meir survival analysis was done for estimation of progression-free survival (PFS) and overall survival (OS). Univariate analysis was done for identifying factors affecting PFS and OS. RESULTS: Out of 141 NHL patients, 67 patients were identified subjected to the inclusion criteria. The median age was 68 years (60–92). Majority were B-cell NHL (86.6%). The commonest subtype in B-cell was diffuse large B-cell lymphoma (55.2%). Fifty-four patients took treatment. The treatment intent was curative in 41 patients (61.2%). Among the patients receiving curative treatment, 16 patients couldn't receive treatment in accordance with NCCN guidelines due to financial issues. Two years PFS was 55%. Two years PFS for B-cell NHL and T-cell NHL were 55% and 50% respectively (P = 0.982). Two years PFS for standard Rx and nonstandard Rx were 62% and 50% respectively, but it didn't reach statistical significance (P = 0.537). Two years OS for the entire cohort was 84%. CONCLUSION: Standard treatment in accordance with guidelines can be delivered in elderly patients irrespective of age. There is a need for creating financial assistance for patients, so that potentially curative treatments are not denied.
Keywords: Elderly, non-Hodgkin's lymphomas, standard treatment
|How to cite this article:|
Nair C K, Patil V M, Raghavan V, Babu S, Nayanar S. Retrospective audit of clinico-pathologic features and treatment outcomes in a cohort of elderly non-Hodgkin's lymphoma patients in a tertiary cancer center. Indian J Cancer 2015;52:541-4
|How to cite this URL:|
Nair C K, Patil V M, Raghavan V, Babu S, Nayanar S. Retrospective audit of clinico-pathologic features and treatment outcomes in a cohort of elderly non-Hodgkin's lymphoma patients in a tertiary cancer center. Indian J Cancer [serial online] 2015 [cited 2020 Aug 3];52:541-4. Available from: http://www.indianjcancer.com/text.asp?2015/52/4/541/178434
| » Introduction|| |
There are data to suggest an increased incidence of non-Hodgkin's lymphomas (NHL) in all parts of the world. The presently used WHO classification is based on morphology, clinical characteristics, and biologic characters. From the various epidemiologic studies all over the world, it has been clear that the major types of NHL are of B-cell origin, and remaining types are of T-cell or natural killer cell origin.,, Median age of patients diagnosed with NHL in western literature is consistently above 60 years; however this is not true for Indian series reporting on NHL.,, There is a general tendency to treat elderly patients with less aggressive treatment approaches which may affect their outcomes., There is evidence in NHL, head and neck cancers, ovarian cancer and breast cancer that suboptimal regimens with lower dose intensity may decrease overall survival (OS).,,,,,, None of the Indian series reporting on NHL have tackled specifically the elderly population.
Since the introduction of Rituximab, the prognosis in B-cell NHL had dramatically improved, but there is not much survival improvement in T-cell NHL over last many years. In developed countries, Rituximab is a routine part in B-cell NHL treatment, whereas in countries like India, due to lack of uniform health insurance facilities, chemotherapy alone, like CHOP regimen, still forms the major treatment. However to what extent these costly therapies are given in elderly patients is questionable?
There no reports from India regarding the approximate incidence, prevalence, epidemiologic characteristics and treatment patterns of NHL in elderly patients in particular, to our knowledge. Hence, we decided to do an audit of elderly NHL patients treated at our center.
| » Methods|| |
This was an institutional review board approved project. At our center treatment for each patient is as per standard NCCN guidelines. The treatment is started after getting approval in the multispecialty board discussion in the institute.
The case records of all newly diagnosed NHL patients presented at our center between the period of December 2010 and December 2013 were reviewed for data collection. There were a total of 141 NHL patients identified of which 67 patients were of the age of 60 or more, and were hence eligible for the study. Case records were reviewed for demographical details, presenting complaints details, B symptoms, staging details, international prognostic index (IPI), biochemical investigations, complete blood counts, peripheral smear, treatment details, response, toxicity details, and efficacy pattern. In addition, dates of progression, relapse or death if applicable was documented. Status of patients at last follow-up was documented.
For this project, the response was quantified according to standard guidelines., The toxicity at each visit was charted according to CTCAE version 4.02. Only the maximum grade of a particular toxicity per patient has been reported. The first-line chemotherapy treatment delivered for each patient was critically reviewed with respect to NCCN guidelines of that year. Patients who were offered treatment which was not in accordance with guidelines were reported as having nonstandard treatment. The reason for nonstandard treatment was noted. OS was calculated from the date of registration to the date of death due to disease or any other cause or date of last follow-up. Progression-free survival (PFS) was calculated from the date of registration to the time of relapse, disease progression, or date of last follow-up. Survival was analyzed by creating Kaplan–Meier curves. Univariate analyses were done for the same. Factors tested were age (below or above 75 years), Eastern cooperative oncology group (ECOG) performance status (PS) (below 2 or above it), cell of origin (B-cell or T-cell) and type of treatment. As multiple factors were tested, Bonferronis correction was applied. The P value considered significant was 0.0125.
| » Results|| |
The median age of the cohort was 68 years (range: 60–92). Details about baseline parameters are in [Table 1]. Thirty-five patients (52.2%) had B symptoms, and 22 (32.8%) had extra nodal involvement. Fifteen patients (22.4%) were diabetic, 13 (19.4%) were hypertensive, 4 patients had coronary artery disease (6%), and 2 (3%) were having hyperlipidemia.
The distribution of various histopathology diagnoses were as shown in [Table 2]. Among non-chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) patients (57 patients), 37 patients (64.9%) had stage III/IV disease. Bulky disease was there in 7 patients (12.3%). Forty-three patients (75.43%) patients had high lactate dehydrogenase levels. Among the 10 CLL/SLL cases, staging details were available for 9 patients. Among the 8 CLL patient, 2 patients had Rai stage 1; 1 patient had Rai stage 2; 3 patients had Rai stage 3; 1 patient had Rai stage 4 and details were missing for 1 patient. Among the two SLL cases, 1 was stage IIIB and the other one was IVBE as per Ann Arbor system. IPI scoring systems were available for 42 patients. Five patients had a low risk, 13 had low intermediate risk, 17 had high intermediate risk while 7 patients had high risk.
[Figure 1] gives the consort diagram of treatment delivered. Out of 67 patients, 13 did not receive any treatment. The reason had been logistics. Among the remaining 54, 41 patients (61.2%) received curative treatment. Out of 41 patients, 25 patients (60.9%) received chemotherapy in accordance with NCCN guidelines. The reason for delivery of nonstandard treatment in the remaining 16 patients was finances. What we mean by nonstandard treatment is that all these 16 patients received NCCN recommended chemotherapy, but rituximab couldn't be administered. None of these 41 patients had received suboptimal dosed chemotherapy. The distribution of various treatment regimens were as shown in [Table 3]. Among patients with T-cell NHL, all 9 patients received CHOP.
Among the total 54 patients who received treatment, 41 completed the planned treatment (75.9%). Reasons for noncompletion included toxicity in 1 patient (1.5%), default (not related toxicity) in 4 patients (23.8%), and progression in 8 patients (11.9%).
Among the 54 patients eligible for response assessment, complete remission was documented in 19 patients (35%), partial response in 7 (12%), stable disease in 1 (1.8%) and progression in 18 (33%), with an overall response rate of 48%.
Treatment was relatively well tolerated in the entire group. Neutropenia occurred in 19 patients (46.3%), with Grade III/IV neutropenia in 8 (19.5%) and febrile neutropenia in only 1 patient (2.4%). Grade I/II peripheral neuropathy was seen in 6 (14.63%). Other toxicities included Grade I/II mucositis in 3 (7.3%), herpes zoster in 3 (7.3%), hyperglycemia and proximal myopathy in 1 patient each.
Average duration of follow-up was 17 months. Two years PFS was 55%. Two years PFS for B-cell NHL and T-cell NHL were 55% and 50% respectively (P = 0.982). Two years PFS for standard Rx and nonstandard Rx were 62% and 50% respectively (P = 0.537) [Figure 2]. The PFS was not affected by age (P = 0.577), cell of origin (P = 0.982), ECOG PS (P = 0.023), and type of treatment (standard vs. nonstandard) (P = 0.537).
|Figure 2: Figure depicting progression-free survival of standard and nonstandard treatment|
Click here to view
Two years OS for entire cohort was 84%. OS for B-cell NHL was 91%, and for T-cell NHL was 57% (P = 0.111). The OS was not affected by age (P = 0.457) [Figure 3], cell of origin (P = 0.982), ECOG PS (0.762) and type of treatment (standard vs. nonstandard) (0.269).
| » Discussion|| |
In this retrospective evaluation, we tried to analyze the various aspects of NHL in a population age of 60 years and above. This age group is specifically considered because the data about this group from India is scarce. Moreover, in all the previously reported series from India, the median age was well below this.,, Furthermore, the median age for all NHL series from India is well below 60 years when compared to the various series form western world. The age of 60 years is taken here as elderly in accordance with the retirement age in India.
About the distribution of different types of NHL, B-cell NHL constituted 86.6% and T-cell NHL, the remaining 13.4%. This is slightly different from a previously reported series from India, as the numbers of B-cells were in the range of 79%, but is similar to another report from India (83.2%)., The overall lower incidence of T-cell NHL in India when compared to other Asian countries is applicable for our cohort also. This is substantiated by reports showing the difference in distribution of various histological subtypes by geographical locations.
The most common histological subtype in our study group was diffuse large B-cell lymphoma (DLBCL) (55.2%). This holds true even in this age group as the previous reports from India, had the majority of NHLs as DLBCL. The second most common type in our series was CLL/SLL (14.9%). This is in contrast to other previous reports from India, and from the western world, as in all reported series, follicular lymphoma was the second common, even though, the absolute numbers were much less than that reported from west. Naresh et al. had described a frequency of 5.6% cases of CLL/SLL. The reason for the higher percentage of CLL/SLL in our cohort is not exactly known, but whether it is simply related to the age factor is a question to be answered. On the other hand, reports from the west where the mean age for NHL patients is like that of our patient series, this was not the case. As expected, considering the age profile, there was not a single case of lymphoblastic lymphoma.
Surprisingly, the number of patients with significant comorbidities was very less in our cohort, even after selecting patients above the age of 59 years. More than three-quarter of our patients were having good PS (0–1). This is in sharp contrast to a previous report from India where only 46% patients had similar ECOG PS.
In our study 19.4% (13) of patients did not take treatment. This was in spite of extensive counseling and shows nihilistic attitude of elderly patients and their family members toward treatment. Among the 41 patients who had curative intent treatment, 16 patients (39% of curative patients) received nonstandard treatment. This nonstandard treatment was non rituximab based treatment this was mainly delivered before the year 2012. In 2012, the institute started giving financial support to needy patients through Karunya benevolent schemes. Such discrepancies in treatment due to unaffordability of costly targeted therapies have been reported in breast and head and neck cancers treatments from developing world., It was a heartening finding that none of the patients were given suboptimal nonstandard treatment on the basis of having elderly status. The proportion of elderly NHL getting suboptimal treatment reported from the Western world is around 76.5%. It's known that elderly patients treated with standard regimens have a favorable prognosis. In our study though, there was a difference of 12% in 2 years PFS between standard and nonstandard treatment recipients this didn't reach statistical significance due to the less number of patients in this analysis. Toxicity in elderly patients has been on the causes for offering suboptimal doses. In our study, none of the patients had received suboptimal doses of chemotherapy. This is important as results from the Dutch survey clearly show that 42.85% of patients receiving optimal chemotherapy receive suboptimal doses. In our study, as it was a retrospective analysis, toxicity noted in case records may have been suboptimal. However, rate of Grade III–IV neutropenia was seen in 19.5% which signifies the need for close monitoring.
This indeed is a very small study, that too retrospective, form a single tertiary care center, located in a rural part of India. However, it provides important insights into the treatment of elderly NHL patients in the country in rural settings.
| » References|| |
Chiu BC, Weisenburger DD. An update of the epidemiology of non-Hodgkin's lymphoma. Clin Lymphoma 2003;4:161-8.
Jaffe ES. The 2008 WHO classification of lymphomas: Implications for clinical practice and translational research. Hematology Am Soc Hematol Educ Program 2009;523-31.
Zheng T, Mayne ST, Boyle P, Holford TR, Liu WL, Flannery J. Epidemiology of non-Hodgkin lymphoma in Connecticut 1935-1988. Cancer 1992;70:840-9.
Mitterlechner T, Fiegl M, Mühlböck H, Oberaigner W, Dirnhofer S, Tzankov A. Epidemiology of non-Hodgkin lymphomas in Tyrol/Austria from 1991 to 2000. J Clin Pathol 2006;59:48-55.
Anderson JR, Armitage JO, Weisenburger DD. Epidemiology of the non-Hodgkin's lymphomas: Distributions of the major subtypes differ by geographic locations. Non-Hodgkin's lymphoma classification project. Ann Oncol 1998;9:717-20.
Advani SH, Banavali SD, Agarwala S, Gopal R, Dinshaw KA, Borges A, et al
. The pattern of malignant lymphoma in India: A study of 1371 cases. Leuk Lymphoma 1990;2:307-16.
Sahni CS, Desai SB. Distribution and clinicopathologic characteristics of non-Hodgkin's lymphoma in India: A study of 935 cases using WHO classification of lymphoid neoplasms (2000). Leuk Lymphoma 2007;48:122-33.
Naresh KN, Srinivas V, Soman CS. Distribution of various subtypes of non-Hodgkin's lymphoma in India: A study of 2773 lymphomas using R.E.A.L. and WHO Classifications. Ann Oncol 2000;11 Suppl 1:63-7.
Peters FP, Lalisang RI, Fickers MM, Erdkamp FL, Wils JA, Houben SG, et al.
Treatment of elderly patients with intermediate-and high-grade non-Hodgkin's lymphoma: A retrospective population-based study. Ann Hematol 2001;80:155-9.
Sarkozy C, Coiffier B. Diffuse large B-cell lymphoma in the elderly: A review of potential difficulties. Clin Cancer Res 2013;19:1660-9.
Chan JK, Kapp DS, Shin JY, Osann K, Leiserowitz GS, Cress RD, et al.
Factors associated with the suboptimal treatment of women less than 55 years of age with early-stage ovarian cancer. Gynecol Oncol 2008;108:95-9.
Palaia I, Loprete E, Musella A, Marchetti C, Di Donato V, Bellati F, et al.
Chemotherapy in elderly patients with gynecological cancer. Oncology 2013;85:168-72.
Patil VM, Noronha V, Joshi A, Muddu VK, Dhumal S, Arya S, et al.
Weekly chemotherapy as Induction chemotherapy in locally advanced head and neck cancer for patients ineligible for 3 weekly maximum tolerable dose chemotherapy. Indian J Cancer 2014;51:20-4.
Versteeg KS, Konings IR, Lagaay AM, van de Loosdrecht AA, Verheul HM. Prediction of treatment-related toxicity and outcome with geriatric assessment in elderly patients with solid malignancies treated with chemotherapy: A systematic review. Ann Oncol 2014.
Mackey RV, Chandru Kowdley G. Treatment practices and outcomes of elderly women with breast cancer in a community hospital. Am Surg 2014;80:714-9.
Griffin MM, Morley N. Rituximab in the treatment of non-Hodgkin's lymphoma – A critical evaluation of randomized controlled trials. Expert Opin Biol Ther 2013;13:803-11.
Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ, et al.
Revised response criteria for malignant lymphoma. J Clin Oncol 2007;25:579-86.
Hallek M, Cheson BD, Catovsky D, Caligaris-Cappio F, Dighiero G, Döhner H, et al.
Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: A report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines. Blood 2008;111:5446-56.
Strassburger K, Bretz F. Compatible simultaneous lower confidence bounds for the Holm procedure and other Bonferroni-based closed tests. Stat Med 2008;27:4914-27.
Yeole BB, Kurkure AP, Koyande SS. Geriatric cancers in India: An epidemiological and demographic overview. Asian Pac J Cancer Prev 2008;9:271-4.
Khera R, Jain S, Kumar L, Thulkar S, Vijayraghwan M, Dawar R. Diffuse large B-cell lymphoma: Experience from a tertiary care center in North India. Med Oncol 2010;27:310-8.
Ignacio DN, Griffin JJ, Daniel MG, Serlemitsos-Day MT, Lombardo FA, Alleyne TA. An evaluation of treatment strategies for head and neck cancer in an African American population. West Indian Med J 2013;62:504-9.
Ghosh J, Gupta S, Desai S, Shet T, Radhakrishnan S, Suryavanshi P, et al.
Estrogen, progesterone and HER2 receptor expression in breast tumors of patients, and their usage of HER2-targeted therapy, in a tertiary care centre in India. Indian J Cancer 2011;48:391-6.
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3]