Promising clinical outcomes of sequential and “Sandwich” chemotherapy and extended involved‐field intensity‐modulated radiotherapy in patients with stage I_E/II_E extranodal natural killer/T‐cell lymphoma

Abstract

BackgroundThe optimal treatment for the rare subtype of non‐Hodgkin lymphoma, extranodal natural killer/T‐cell lymphoma (ENKTL), nasal‐type, has not been clearly defined. The purpose of the study was to investigate the efficacy of sequential and “Sandwich” chemotherapy and extended involved‐field intensity‐modulated radiotherapy (IMRT) in patients with stage IE/IIE extranodal ENKTL, nasal‐type.MethodsOne hundred and fifty‐five patients with stage IE/IIE nasal‐type ENKTL were enrolled in the study, including 99 patients treated with sequential chemotherapy and extended involved‐field IMRT (SCRT) and 56 patients with “Sandwich” chemotherapy and extended involved‐field IMRT and chemotherapy (SCRCT). All patients were treated with extended involved‐field IMRT with median dose of 54.6 Gy to the primary tumor and positive lymph nodes. Ninety‐four patients had Ann Arbor stage IE disease, and 61 patients had stage IIE disease.ResultsThe 5‐year rates of loco‐regional recurrence (LRR), progression‐free survival (PFS), and overall survival (OS) were 17.0%, 78.5%, and 84.7%, respectively. Univariate analysis revealed that EBV DNA copy after treatment (normal vs elevated level) was significant prognostic factor for LRR, PFS, and OS (P < 0.001); therapeutic method (SCRT vs SCRCT) was significant prognostic factor for PFS (71.0% vs 91.8%, P = 0.011), but there was no significant effect on 5‐year LRR and OS (22.2% vs 8.2%, P = 0.051 for LRR; 80.9% vs 91.8%, P = 0.199 for OS).ConclusionsCompared with SCRT, SCRCT was significantly associated with higher PFS rates and showed a trend toward improved loco‐regional control. EBV DNA copy after treatment is a good index for recurrence and prognosis for stage IE/IIE ENKTL patients.

A phase II study of sintilimab, anlotinib, and pegaspargase sandwiched with radiotherapy as first‐line therapy in patients with newly diagnosed, stage I–II extranodal natural‐killer/T‐cell lymphoma

“…CTV2 included the corresponding neck lymphatic drainage area; the upper cervical lymph node was included when nasopharynx or retropharyngeal lymph node was involved and the whole cervical lymph node was included when an upper cervical lymph node was involved. 34 Additional three cycles of systemic therapy with the same regimen were given after radiotherapy. Patients discontinued the study in case of disease progression, death, intolerable toxicity, or withdrew consent.…”

“…CTV1 included GTV and adjacent structures in risk, such as nasal mucosa, nasopharyngeal mucosa, retropharyngeal lymph nodes, the Waldeyer's ring, and ethmoid sinus. CTV2 included the corresponding neck lymphatic drainage area; the upper cervical lymph node was included when nasopharynx or retropharyngeal lymph node was involved and the whole cervical lymph node was included when an upper cervical lymph node was involved 34 . Additional three cycles of systemic therapy with the same regimen were given after radiotherapy.…”

Etoposide, dexamethasone, and pegaspargase with sandwiched radiotherapy in early-stage natural killer/T-cell lymphoma: A randomized phase III study

“… 19 Sandwiched radiotherapy showed significantly higher PFS rates and a trend toward improved loco-regional control when compared with sequential chemotherapy and radiotherapy. 21 Therefore, to maximize disease control while minimizing toxic effects, further exploration of optimal low-intensity regimens with sandwiched radiotherapy in early-stage NKTCL based on randomized, phase III clinical trials remains of great interest.…”

Efficacy of a short sandwich protocol, methotrexate, gemcitabine, L‐asparaginase and dexamethasone chemotherapy combined with radiotherapy, in localised newly diagnosed NK/T‐cell lymphoma: A French retrospective study

“…[7][8][9][10] In addition, both sequential chemotherapy and radiotherapy and concurrent chemoradiotherapy (CCRT) have shown efficacy in patients with localised disease. [11][12][13][14][15][16][17][18] Moreover, new chemotherapeutic protocols including gemcitabine, a Pgp insensitive drug, have given promising results, with improved overall response rate (ORR) and survival with tolerable toxicity. 10,[19][20][21][22] Based on these results, current treatment for localised ENKTL usually includes radiotherapy and chemotherapy with L-asparaginase but the optimal treatment modality has not yet been defined.…”

“…Recently, L‐asparaginase (L‐aspa)‐based regimens, including SMILE and AspaMetDex protocols, improved the prognosis of ENKTL patients, particularly in patients with disseminated disease, resulting in 3‐year overall survival (OS) from 56%–67% and 3‐year progression‐free survival (PFS) from 36%–39% 7–10 . In addition, both sequential chemotherapy and radiotherapy and concurrent chemoradiotherapy (CCRT) have shown efficacy in patients with localised disease 11–18 . Moreover, new chemotherapeutic protocols including gemcitabine, a Pgp insensitive drug, have given promising results, with improved overall response rate (ORR) and survival with tolerable toxicity 10,19–22 …”