Hematology/Oncology Clinical Practice Guidelines: 2018 Midyear Review

John Anello; Brian Feinberg; John Heinegg; Yonah Korngold; Richard Lindsey; Cristina Wojdylo; Olivia Wong, DO


July 09, 2018

In This Article

Extranodal NK/T-Cell Lymphomas

National Comprehensive Cancer Network

Participation in a clinical trial is the preferred option for all patients with extranodal natural killer/T-cell lymphomas (ENKL) with any stage disease. It is recommended that patients with ENKL be treated at centers with expertise in the management of this disease and, when possible, enrolled in clinical trials.

ENKLs can have an extranasal presentation, with skin, testis, and gastrointestinal tract being the most common sites of extranasal involvement or metastatic disease.

Biopsy specimens should include edges of the lesions to increase the odds of having viable tissue. It may also be useful to perform multiple nasopharyngeal biopsies for the evaluation of occult disease even in areas that are not clearly involved on endoscopic examination. Adequate immunophenotyping is essential to confirm the diagnosis.

Epstein-Barr virus (EBV) infection is always present in ENKL and should be determined using EBV-encoded RNA in situ hybridization (EBER-ISH).

Measurement of EBV-DNA load and calculation prognostic index (PINK or PINK-E) is recommended as part of initial workup.

Measurement of EBV DNA viral load using quantitative PCR is useful in the diagnosis and often in the monitoring of disease. EBV DNA viral load correlates well with clinical stage, response to therapy, and poor survival.

RT alone is recommended for patients with stage I or II nasal disease who are unfit to undergo chemotherapy. Patients with stage I or II nasal disease who are fit to receive chemotherapy can be treated with concurrent chemoradiation (RT, 50 Gy, and 3 courses of DeVIC [dexamethasone/etoposide/ifosfamide/carboplatin] or RT, 40–52.8 Gy, and cisplatin followed by 3 cycles of VIPD [etoposide/ifosfamide/cisplatin/dexamethasone]) or sequential chemoradiation (modified SMILE [dexamethasone/methotrexate/ifosfamide/L-asparaginase/etoposide] followed by RT, 45–50.4 Gy) or sandwich chemoradiation (2 cycles of P-GEMOX [pegaspargase/gemcitabine/oxaliplatin] followed by RT, 56 Gy, followed by 2–4 cycles of P-GEMOX).

ENKL cells are associated with a high expression of P-glycoprotein, leading to multidrug resistance that is likely responsible for the poor response to conventional anthracycline-based chemotherapy.

Retrospective comparative studies have shown that asparaginase- and pegaspargase-based regimens are associated with superior efficacy compared with conventional anthracycline-based regimens for the treatment of stage I–II disease, with pegaspargase-based regimens preferred.

ISRT (involved-site RT) is recommended as the appropriate field because it limits the volume of RT to the region of involvement only. An ISRT dose of 50 to 55 Gy is recommended when used alone as primary treatment, and 45 to 50.4 Gy is recommended when used in combination with chemotherapy.

When ISRT is used alone, the clinical target volume (CTV) should encompass the involved region as defined by MRI and CT, with expansions to include any of the sinuses that were partially involved initially, all adjacent paranasal sinuses, and a 0.5- to 1.0-cm expansion into soft tissue. In instances when chemotherapy was given before ISRT and has produced a CR, the CTV should include at least the prechemotherapy gross tumor volume with appropriate margins (0.5-1.0 cm).

Patients with stage IV nasal disease and those with extranasal disease (stage I–IV) can be treated with pegaspargase-based combination chemotherapy (AspaMetDex [L-asparaginase/methotrexate/dexamethasone], modified SMILE, or P-GEMOX regimen) with or without RT, or concurrent chemoradiation (RT, 50 Gy, and 3 courses of DeVIC, or concurrent RT, 40–52.8 Gy, and cisplatin followed by 3 cycles of VIPD). Pegaspargase-based combination chemotherapy alone may be appropriate for selected patients who are not eligible to receive RT. The P-GEMOX regimen is an option for patients who cannot tolerate intense chemotherapy.



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