Lymphoma – A Basic Understanding
This interview was published originally in www.oncofocus.com on 12th September 2019
Cancer awareness is a continuous exercise that requires a multi-dimensional approach and the proactive involvement of every stakeholder. Oncofocus, is a management consulting and research firm, will be publishing every month a short interview with leading Oncologists across the APAC region on a particular Cancer type. The main objective of these interviews is to learn the "What, Why, How" of the present state of cancer management directly from the treaters.
September being the Lymphoma Awareness Month, we decided to focus on lymphoma, in the second post of our cancer interview series. Our analyst Ms. Shilna Kunnath connected with Dr. Anil Kumar MR, consultant radiation oncologist and CEO of Bangalore Cancer Centre, and discussed about lymphoma in general.
Dr . Anil Kumar M R.
MBBS, MD, DNB.
Consultant Radiation Oncologist
Fortis hospital, BG Road, Bengaluru
CEO, Bangalore Cancer Centre, Bengaluru
We understand that most cancers are manageable if they are identified at an early stage. So, for someone to get an early diagnosis, are there any early signs and symptoms to look for lymphoma?
Dr. Anil Kumar M R: Lymphoma patients usually present to the OPD with the most common signs such as lymph node swelling, lumps in the neck, armpit, or in the groin. Additionally, patients will also present with the issue of B symptoms - fever, night sweats, loss of weight, and loss of appetite.
If the lymph node swelling is quite massive, depending on the location of the lymph nodes, there will be pain and other associated symptoms. For example, if the lymph node is present in the chest cavity and is pressing the respiratory airway, then patients come with stridor. Similarly, if the lymph nodes are in the mediastinum, then the patient presents with respiratory obstruction, and if the lymph nodes are in the abdomen, then they come with pain in the abdomen or cramp.
So, the most common early symptoms of lymphoma would be lymph node swelling, lumps in the neck/armpit/groin, fever, night sweats, itching, weight loss.
What are your suggestions to increase the early diagnosis of lymphoma?
Dr. Anil Kumar M R: Suppose any patient comes with any lymph node swelling, which is the most common presentation, ideally in the Indian scenario, we expect it to be tuberculosis. So we ask the patient to get lymph node excisional biopsy, and if any unnatural weight loss (more than 10% weight loss within 3 – 6 months) or any history of fever without any foci of infection or if the patient is profoundly sweating and drenching, especially night sweats, then will ask them to get evaluated with blood tests like complete blood count.
So, suppose there is a lymphoma there will be altered blood counts. And if such a patient comes to a clinician and gets neck/armpit/groin examination, wherever lymph nodes are positive, the clinician will order a lymph node excisional biopsy. Excisional biopsy is precise, so it is always advised to go for it rather than a general biopsy. An excisional biopsy will help to identify the type of lymphoma i.e., Hodgkin’s lymphoma or Non-Hodgkin’s lymphoma. There are many varieties of lymphomas. Ideally, we recommend Immunophenotype IHC, CD marker, to find out the specific lymphoma type. So, the first step would be lymph node excisional biopsy and over that, if we find it to be lymphoma, then we will go for Immunophenotype and CD marker.
Are these enlarged lymph nodes painful?
Dr. Anil Kumar M R: No, according to the textbook, it should be a painless swelling that feels like a rubbery movable mass. But if lymph nodes are enormous and are obstructing the surrounding structures like pressing the nerves/blood vessel/airways/food pipe, then pain and other symptoms will appear. Ideally, it should be a painless, lymph node swelling with a rubbery consistency, but if a small lymph node is painful, then it is an infection.
So, doctor, will there be multiple enlarged lymph nodes?
Dr. Anil Kumar M R: It can be one single lymph node or multiple enlarged lymph nodes. For example, if there is lymphoma in the cervical lymph node and is in an advanced stage (II or III) then enlarged lymph nodes appear in the angular, armpit, and groin.
Based on the number of lymph nodes, we classify the stage of lymphoma and while naming cancer - the position of the node - above or below the diaphragm; the presence or absence of B symptoms; involvement of spleen, and any involvement of any extra lymph nodal organs(or extra-nodal organs) – are considered.
Who are at risk of developing lymphoma? Is there any specific population having more risk of contracting lymphoma?
Dr. Anil Kumar M R: There are modifiable and non-modifiable factors. Lifestyle factors like alcohol consumption, smoking, etc. are modifiable factors. The presence of Epstein-Barr virus, HIV infections, and auto-immune disorders are risk factors. Patients with immune suppression due to any underlying disease are at high risk of developing lymphoma.
Lymphoma develops in pediatrics, middle age, and geriatric populations. Lymphoma is classified into different types like T-cell, B-cell, and some of these sub-types are more common at a young age, and some are common in elderly age. Otherwise, lymphoma usually does not have any correlation with race.
Could you elaborate more about the classification?
Dr. Anil Kumar M R: Normally, we classify lymphomas as Hodgkin’s lymphoma and Non-Hodgkin’s lymphoma. This is a broader classification.
Hodgkin’s is a good one as it can be better controlled. In Hodgkin’s lymphoma, again we have Classical type and Non-classical. Similarly, Non-Hodgkin’s also has multiple sub-types, and according to the WHO classification, currently, there are more than 100 varieties like T-cell and B-cell lymphomas. Within B - cell, we again have Chronic lymphocytic leukemia (CLL), Small lymphocytic leukemia (SLL), Mantle cell lymphoma (MCL), etc.
What is the prognosis? What are the common treatment options?
Dr. Anil Kumar M R: Treatment option depends on the stage and type of lymphoma. As discussed earlier, in Hodgkin lymphoma, the prognosis is good; if the patient receives the standard ADVD regimen and radiation therapy, they will have survival of up to 15 -20 years.
But inNon-Hodgkin’s lymphoma, the prognosis depends on sub-type. A B-cell lymphoma has a good prognosis compared to a T-cell variant. Again, in B-cell lymphomas, we have varieties based on the type of CD marker expressed. If the lymphoma is CD20 positive, then ideally, we use something called immunotherapy or targeted therapy. We use rituximab, an anti CD20 monoclonal antibody. It does not have broad-spectrum side effects like chemotherapy. Sometimes, rituximab is given along with the STOP chemotherapy regimen, called R-STOP, which will be followed by radiotherapy. If the lymph node is very bulky, we give something called Involved field Radiotherapy (IFRT). There is no scope of surgery in lymphoma, but the treatment is usually multi-modal – chemotherapy + immunotherapy/targeted therapy +/- radiotherapy. The only exception is in the case of a massively enlarged spleen, where splenectomy is performed. The surgeon's help is required only with splenectomy and lymph node excision biopsy.
What would be the survival rate for patients who have lymphoma
Dr. Anil Kumar M R: It is difficult to quote a survival rate across the spectrum from lymphomas. The survival rates vary based on the lymphoma subtype, stage of the disease, patient age, etc. Generally, the earlier the stage of detection, the better the prognosis.
If you consider100 patients who received multi-modal therapy, then 80 - 90 Stage I patients, 70 - 80 Stage II patients, and 50 - 60 Stage III patients will have 5-year disease-free survival. As the stage increases the 5-year disease-free survival and overall survival will come down.
Do you foresee any interesting trends in terms of lymphoma space?
Dr. Anil Kumar M R: If we talk about new developments in terms of upcoming therapies, then we should speak of immunotherapies. The advent of rituximab itself changed the prognosis of Non-Hodgkin’s lymphoma. Being a very specific, chimeric monoclonal antibody, it targets only the cells expressing CD20 marker. It will not have any side effects on any other cells when compared to chemotherapy. This is the reason they are called targeted therapies.
In simple terms, the use of rituximab and other molecular agents is like firing a gun to kill a terrorist among the crowd, whereas, chemotherapy is dropping a bomb on the entire crowd. So, with a gun (targeted agents), civilians (healthy cells) are spared, and only terrorists (cancer cells) are killed.
Like rituximab, there are several other newer targeted therapies currently being evaluated in the clinical trials.
Coming to radiotherapy, initially, we used to have cobalt-based radiotherapy which produced heavy radiation. Patients who survive for 10 – 15 years after radiotherapy, used to come back with radiation-induced secondary malignancies after 15 – 20 years. However, now, with the evolution of radiation machines such as linear accelerators, we can accurately hit the enlarged lymph nodes without damaging the surrounding tissue. Surely, it is a good development, and the use of linear accelerators is the current trend in terms of radiotherapy.
In terms of epidemiology, I don’t see any changes. The risk factors also remain the same – viral infections, immuno-suppressed patients, and lifestyle factors. The only difference is in terms of better treatment options and improved radiation machinery.
Thank you for the inputs doctor.
Dr. Anil Kumar M R: Welcome! Thank you for inviting me to this discussion.