Why International Patients Choose India for Primary CNS Lymphoma Care

Primary CNS lymphoma

The primary CNS lymphoma (PCNSL) is a relatively rare, aggressive non-Hodgkin lymphoma, occurring in the brain, spinal cord, leptomeninges, or eyes, without evidence of 1 systemic disease at the time of detection. It makes up approximately 3-4 percent of all brain tumors, and most frequently a DLBCL.

Primary CNS lymphoma treatment

General Principles:

• Surgery does not cure (can only be biopsied).
• CNSL is very sensitive to chemotherapy, and to radiotherapy.
• Treatment is age-, performance status- and immune status-dependent.

First-Line Treatment

High-Dose Methotrexate (HD-MTX) based Chemotherapy:

• Backbone of therapy -administered IV in high doses (>3.5 g/m 2 ), can cross blood-brain barrier.

When used together with:

• Cytarabine
• Rituximab (anti-CD20 monoclonal antibody)
• In some regimens, temozolomide / thiotepa.

Regimens:

• MTR (MTX, Cytarabine, Thiotepa, Rituximab) - young fit patients.
• HD-MTX – with Cytarabine.

Corticosteroids (e.g. dexamethasone)

• Reduce reduction of edema and symptoms.
• Supportive therapy, but should not be used before biopsy where possible (can make tumor smaller and difficult to assess).

Consolidation Therapy

• Is in an effort to reduce relapse after induction chemo.

Options include:

• Auto stem cell transplant (ASCT)
• Suitable in younger fit patients.
• Stem cell rescue by high dose chemotherapy.

Whole brain Radiotherapy (WBRT)

• Effective with adverse effect of associating to neurocognitive loss especially among patients over the age of 60 years.
• Administered sparingly (e.g. relapse or where a transplant is impossible).
• In selected cases, non myeloablative chemotherapy (e.g. low dose cytarabine, etoposide).

Recurrent / Refractory PCNSL

• Rechallenge with HD-MTX in case of good response already.
• WBRT (unless utilized in the first place).
• Novel/targeted therapies in development
• Ibrutinib (BTK inhibitor)
• Lenalidomide / Pomalidomide
• CAR-T cell therapy (trial).

Supportive Care

• Anticonvulsants (should seizures exist).
• Therapy of increased pressure in the genesis (mannitol, steroids).
• Rehabilitation (rehabilitating speech/physical therapy).
• Check-up ophthalmology (ocular lymphoma).

Primary CNS lymphoma diagnosis

Clinical Suspicion

The patients commonly present with:

• Focal neurological symptoms (weaknesses, speech/vision impairments).
• Cognitive or behavioral change
• And headache, and nausea, and vomiting (increased intracranial pressure).
• Seizures (rarely).
• Ocular manifestations (blurred vision, floaters) in symptoms of ocular involvement.

Imaging

• MRI Brain with contrast
• First-line imaging.

Typical findings:

• Solitary or multiple lesions that are homogenously enhancing
• Frequently extensive: periventricular white matter, basal ganglia, corpus callosum and thalamus.
• On DWI, restricted diffusion.
• Less necrosis/ hemorrhage when compared to glioblastoma or metastasis.

Other Imaging

• Spinal MRI - when the patient presents with symptoms of a spinal involvement
• PET-CT/CT chest, abdomen, and pelvis to exclude the presence of systemic lymphoma (need to confirm that it is primary CNS).

Tissue Diagnosis

• Stereotactic brain biopsy
• Gold standard to diagnose.
• Confirms lymphoma histology (majority of them are Diffuse Large B-cell Lymphoma, DLBCL).
• The only notable exception is that corticosteroids should not be administered prior to biopsy, which can result in shrinkage of the tumor that makes diagnosis difficult.

CSF Studies

• Lumbar puncture (with the exclusion of raised ICP).

Tests:

• Cytology (so as to detect malignant lymphocytes).
• Flow cytometry (sensitive).
• Molecular (immunoglobulin gene rearrangements).

Ophthalmologic Evaluation

• Lit-lamp biomicroscopy + biopsy of vitreous when ocular is seen.
• Approximately 20-25 percent of PCNSL patients get affected by the eye.

Laboratory Work-up

• PCNSL occurs more frequently in immunocompromised individuals and this could be due to infection with HIV.
• There is relevance in the use of EBV testing in patients with immune deficiency.
• Basic laboratory work (CBC, kidney, liver) will be performed before a chemotherapy plan is put into session.

Diagnostic Criteria (Summarised)

• When an individual experiences loss of neurons, the diagnosis of PCNSL is made.
• Lymphoma in CNS /ocular tissue typically DLBCL is confirmed by histopathology.
• No systemic lymphoma detected in staging tests (PET-CT/CT scans, bone marrow in case of indication).

Primary CNS lymphoma symptoms

Neurological Symptoms:

• Focal deficits (depend on the site of the tumor):
• Weakness, or paralysis (motor weakness).
• Loss of sensation or burning (hypesthesia).
• Wage/ money problems (aphasia).
• Blinking problems (field cuts, double vision).

Cognitive / Behavioral Alteration:

• Memory loss.
• Confusion, disorientation.
• Behavioral changes or personality change
• Lack of attention and focus.

Increased ICP:

• Headaches (generally getting worse in the morning).
• Nausea, vomiting.
• Papilledema (swelling of disc of eye).
• Seizures
• Less common than other brain tumors (10-20 percent of patients).

Eye Symptoms (when parts of eyes are affected):

• Blurred vision.
• Floaters.
• Redness or pain of the eye (less frequent).
• In severe cases this may result in vision loss.

Involvement of the Spinal Cord (uncommon):

• Back pain.
• Weak legs.
• Dysfunction of the bowel/bladder

Systemic Symptoms

• Typically negative, as PCNSL by strict definition involves the confinement of the disease to the CNS/eyes.
• Presence of hemorrhage and coined eye 3 weeks earlier → this may indicate secondary CNS lymphoma as a possibility.

Primary CNS lymphoma chemotherapy

Place of Chemotherapy:

• The backbone of PCNSL treatment (surgery in biopsy only; radiotherapy restricted with cognitive adverse effects).
• Needs agents that penetrate the blood brain barrier.
• Administration is usually as induction (initial treatment) and in consolidation.

Induction or First-Line Chemotherapy

Methotrexate (HD-MTX)

• Stem of all regimens.
• It needs rehydration after which there should be alkalinization of urine with the use of leucovorin rescue to avoid toxicity.
• Response rate 50-70 percent.

Combination Regimens:

• MTX alone: in elderly patients, weak patients.
• HD-MTX with Cytarabine (Ara-C): increases response.

MATRix regimen (administered in younger and able bodied patients):

• Methotrexate,
• Cytarabine,
• Thiotepa,
• Rituximab.
• High response, more survival rate of modern regimens.

Other combinations:

• R-MPV (Rituximab, MTX, Procarbazine, Vincristine).
• MTX, Temozolomide + DHA.

Consolidation Therapy (Second Course)

In the case of remission in induction chemo:

• High dose therapy + Autologous Stem Cell Transplantation (ASCT) -recommended in young fit patients.
• Whole Brain Radiotherapy (WBRT) -great results but not used in the elderly because of the neurotoxicity.
• High -dose non-myeloablative chemotherapy (such as cytarabine/etoposide) in selected cases.

Recurrent / Refractory PCNSL

• Rechallenge (HD-MTX) (when prior response was good).
• Cytarabine, Temozolomide, Topotecan can be used as salvage agents.

Investigational targeted therapies:

• BTK inhibitor (brutinib, Ibrutinib).
• Pomalidomide / Lenalidomide (Immunomodulatory drugs).
• CAR-T cell therapy (trails).

Supportive Measures During Chemo

• MTX leucovorin rescue
• Hydration + alkalinization (to avert renal toxicity).
• Renal/ liver monitoring.
• Corticosteroids (to relieve edema/symptoms).
• Prevention of infection (particularly intensive regimens) prophylaxis.

Best hospitals for primary CNS lymphoma care

• Artemis Hospital, Gurgaon
• Medanta-The Medicity, Gurgaon
• Fortis Memorial Research Institute, Gurgaon
• Max Hospital, Saket

Factors Affecting Primary CNS lymphoma treatment cost in India

The key factors influencing the cost of treating Primary CNS Lymphoma (PCNSL) in India:

• Treatment Complexity & Modality
• Hospital Type & Location
• Diagnostic & Supportive Care Expenses
• Drug Sourcing & Generics
• Non-Medical Costs
• Stage of Disease & Treatment Duration

Top doctors for primary CNS lymphoma treatment

• Dr. Priya Tiwari
• Dr. Ashok Kumar Vaid
• Dr. Kunjahari Medhi
• Dr. Rahul Bhargava
• Dr. Vinod Raina
• Dr. Rayaz Ahmed

Primary CNS lymphoma treatment in India by GetWellGo

GetWellGo is regarded as a leading supplier of healthcare services. We help our foreign clients choose the best treatment locations that suit their needs both financially and medically.

We offer:

• Complete transparency
• Fair costs.
• 24 hour availability.
• Medical E-visas
• Online consultation from recognized Indian experts.
• Assistance in selecting India's top hospitals for Primary CNS Lymphoma treatment.
• Expert oncologists with a strong track record of success
• Assistance during and after the course of treatment.
• Language Support
• Travel and Accommodation Services
• Case manager assigned to every patient to provide seamless support in and out of the hospital like appointment booking
• Local SIM Cards
• Currency Exchange
• Arranging Patient’s local food