Extranodal NK/T Cell Lympoma, Nasal Type – Mini Review

Author: Sujeet Kumar @sujeethemat

Some Salient points:-
[1] Approximately 70-75% cases are diagnosed in Limited stage (Stage I and II)
[2] Median Age at presentation = 50 years
[3] Delition 6q21 is MC cytogenetic aberation.
[4] Presence of EBV is almost universal (>90%)

Q1. Why concept of upfront RT or concurrent CT and RT has evolved in its treatment ?
Answer:- These lymphomas are intrinsically chemo resistant and its partly due to high expression of P glycoprotein in NK cell neoplasms.
So approach can be of
A = RT alone
B = Early RT + Chemotherapy
C = Chemotherapy + Late RT
Among these Early RT + Chemotherapy has been found to be best approach by Japnese and Korean groups !!

Note >>> Optimal RT dose for these lymphomas are >/= 50 Gy

[1] CCRT (50Gy) and DeVIC [CR=75%, 5 Year PFS=65%, OS=75 %]
[2] CCRT (50Gy + Cisplatin) followed by VIPD [CR=75%, 5 Year PFS=60%, OS=65%]
[3] SCRT = GELOX (2 Cycle) + RT (56Gy) + GELOX (2-4 Cycle) [CR=75%, 5 Year PFS =75%, OS=75%]
NOTE >> Although NCCN lists SMILE followed by RT as a SCRT option of limited stage disease but no prospective study has evaluated this approach and SMILE is highly toxic regimen.

CCRT = Concurrent chemotherapy and radiotherapy
SCRT = Sequential chemotherapy and radiotherapy
DeVIC = Dexa + Etoposide + Ifosphamide + Carboplatin
VIPD has same componetnts as DeVIC except carboplatin is replaced by cisplatin.
GELOX – Gemcitabine + L-Asparginase + Oxaliplatin

Q2. How is treatment of advanced stage (III and IV) disease different from limited stage disease as RT is not a option and these tumors are intrinsically chemo resistant ?
Answer: Introduction of L-Asparginase into chemotherapy regimes have shown to improve outcome in advanced stage disease.

SMILE Regimen (Steroid + Methotrexate + Ifosfamide + L-Asparginase + Etoposide) for newly diagnosed Stage III, IV and R/R disease !
Schedule: x 2 or More cycles every 28 days !
[5 Year OS of 40-50% has been reported with this regimen]
NOTE> This is highly toxic regimen and >90% experience neutropenia with 30% having life threatning infections so must be given only in advanced cancer centres!

Role of Consolidative Auto SCT or Allo SCT: Survival outcomes for upfront Auto SCT and Allo SCT after currently used treatment regimes is not superior to currently used CT or CT+RT approaches hence upfront Auto or Allo SCT is not recommended as standard therapy in ENKL.

Prognostic factors for ENKL = EBV DNA titer in blood at diagnosis defines outcome as one study has shown 3 year OS of 90% vs 45% in those with detectable EBV-DNA in blood vs those without detectable EVB-DNA in blood.

Prognostic factors for ENKL = PINK (Prognostic index for NK cell Lymphoma) – Age, Stage, Non nasal type, distant LN involvement).

Using PINK model:

  • Low risk (No risk factor) has 3 year OS = 80%
  • Intermediate risk (one risk factor) has 3 year OS 60%
  • High risk (two or more risk factor) has 3 year OS 25%

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