Qing-Feng Liu

Clinical features and treatment outcome of nasal-type NK/T-cell lymphoma of Waldeyer ring

The clinical characteristics and prognosis remain unclear for nasal-type NK/T-cell lymphoma of Waldeyer ring (WR-NKTL). The aim of this study is to determine the clinical features and outcome. Ninety-one patients with WR-NKTL were reviewed. According to the Ann Arbor system, 15, 56, 12, and 8 patients had stage I, II, III, and IV. Of patients with stage I and II, 54 received combined chemotherapy and radiotherapy (CMT), 13 received radiotherapy alone, and 4 patients received chemotherapy alone. All 20 patients with stage III/IV received primary chemotherapy. The disease is characterized by predominance in young males, good performance, a propensity for nodal involvement, frequent stage II through IV diseases, low frequency of elevated LDH, low-risk international prognostic index (IPI), high sensitivity to radiotherapy, and intermediate sensitivity to chemotherapy. The 5-year overall survival and progression-free survival for all patients were 65% and 51%, respectively. The age, B symptoms, stage, and IPI were important prognostic factors. CMT tended to improve the survival compared with radiotherapy alone for patients with stage I and II diseases. Both nodal involvement and distant extranodal dissemination were the primary failure patterns. WR-NKTL appears to have distinct clinical characteristics and favorable outcomes.

Radiotherapy alone with curative intent in patients with stage I extranodal nasal-type NK/T-cell lymphoma.

PURPOSE This study aims to evaluate the outcome and pattern of failure in a large cohort of patients with Stage I NK/T-cell lymphoma of the upper aerodigestive tract treated with radiotherapy alone. METHODS AND MATERIALS The pathological diagnosis was confirmed using standard criteria. All patients were treated with high-dose extended-field radiotherapy alone. The median dose was 50 Gy. The primary tumor was located in the nasal cavity (n = 80), Waldeyer ring (n = 5), or oral cavity (n = 2). RESULTS The overall response to radiotherapy was achieved in 85 of 87 (97.7%) patients, with a complete response rate of 95.4% and a partial response rate of 2.3%. The 5-year overall survival, progression-free survival, and local control rates for all patients were 80%, 69%, and 93%, respectively. Twenty patients (23%) had disease progression or relapse. Of these, 15 patients (17%) developed systemic extranodal disseminations, whereas only 4 (5%) patients had local relapse and 4 (5%) patients had lymph node relapse. CONCLUSIONS Our study suggests that high-dose extended-field radiotherapy alone is a curative therapy and shows favorable clinical outcome in patients with Stage I disease. With the high possibility of local control and primary failure of systemic dissemination, the integration of optimal radiotherapy with more effective systematic therapy is warranted to bring additional improvement to the outcome for these patients.

Variable Clinical Presentations of Nasal and Waldeyer Ring Natural Killer/T-Cell Lymphoma

Purpose: To determine the clinical characteristics, prognosis, and treatment outcome for patients with nasal natural killer (NK)/T-cell lymphoma (N-NKTL) and Waldeyer ring NK/T-cell lymphoma (WR-NKTL). Experimental Design: A total of 145 patients with N-NKTL and 95 patients with WR-NKTL were compared. Results: Compared with N-NKTL, WR-NKTL exhibited distinct differences in clinical features with a propensity for nodal involvement, more advanced stages, low elevated lactate dehydrogenase, intermediate chemosensitivity, and a favorable prognosis. Compared with patients with WR-NKTL, patients with N-NKTL were associated with a lower overall response (54% versus 89%) and higher persistent or progressive disease after initial chemotherapy (46% versus 11%; P = 0.000). The 5-year overall survival and progression-free survival rates were 67% and 56% for N-NKTL and 65% and 47% for WR-NKTL, respectively. Patients with stage II WR-NKTL showed favorable prognosis compared with those with stage II N-NKTL. Compared with radiotherapy alone, patients with early-stage WR-NKTL that received radiotherapy and chemotherapy showed a superior progression-free survival and improved overall survival. In contrast, the addition of chemotherapy to radiotherapy did not provide any survival benefit for patients with early-stage N-NKTL. Conclusions: N-NKTL and WR-NKTL represent heterogeneous groups with variable clinical features, responses, prognosis, and treatment options.

Primary radiotherapy showed favorable outcome in treating extranodal nasal-type NK/T-cell lymphoma in children and adolescents

Extranodal nasal-type natural killer (NK)/T-cell lymphoma is rarely observed in children and adolescents. We aim to investigate the clinical features, prognosis, and treatment outcomes in these patients. Thirty-seven patients were reviewed. There were 19, 14, 2, and 2 patients with stage I, stage II, stage III, and stage IV diseases, respectively. Among the patients with stage I and II disease, 19 patients received initial radiotherapy with or without chemotherapy, and 14 patients received chemotherapy followed by radiotherapy. The 4 patients with stage III and IV disease received primary chemotherapy and radiation of the primary tumor. Children and adolescents with extranodal nasal-type NK/T-cell lymphoma usually presented with early-stage disease, high frequency of B symptoms, good performance, low-risk age-adjusted international prognostic index, and chemoresistance. The complete response rate after initial radiotherapy was 73.7%, which was significantly higher than the response rate after initial chemotherapy (16.7%; P = .002). The 5-year overall survival (OS) and progression-free survival (PFS) rates for all the patients were 77.0% and 68.5%, respectively. The corresponding OS and PFS rates for patients with stage I and II disease were 77.6% and 72.3%, respectively. Children and adolescents with early-stage extranodal nasal-type NK/T-cell lymphoma treated with primary radiotherapy had a favorable prognosis.

Clinical implications of plasma Epstein-Barr virus DNA in early-stage extranodal nasal-type NK/T-cell lymphoma patients receiving primary radiotherapy

The clinical value of plasma Epstein-Barr virus (EBV) DNA has not been evaluated in patients with early-stage extranodal nasal-type NK/T-cell lymphoma (NKTCL) receiving primary radiotherapy. Fifty-eight patients with stage I disease and 11 with stage II disease were recruited. High pretreatment EBV-DNA concentrations were associated with B-symptoms, elevated lactate dehydrogenase levels, and a high International Prognostic Index score. EBV-DNA levels significantly decreased after treatment. The 3-year overall survival (OS) rate was 82.6% for all patients. Stage I or II patients with a pretreatment EBV-DNA level of ≤ 500 copies/mL had 3-year OS and progression-free survival (PFS) rates of 97.1% and 79.0%, respectively, compared with 66.3% (P = .002) and 52.2% (P = .045) in patients with EBV-DNA levels of > 500 copies/mL. The 3-year OS and PFS rates for patients with undetectable EBV-DNA after treatment was significantly higher than patients with detectable EBV-DNA (OS, 92.0% vs 69.8%, P = .031; PFS, 77.5% vs 50.7%, P = .028). Similar results were observed in stage I patients. EBV-DNA levels correlate with tumor load and a poorer prognosis in early-stage NKTCL. The circulating EBV-DNA level could serve both as a valuable biomarker of tumor load for the accurate classification of early-stage NKTCL and as a prognostic factor.

Mild Toxicity and Favorable Prognosis of High–Dose and Extended Involved-Field Intensity-Modulated Radiotherapy for Patients With Early-Stage Nasal NK/T-Cell Lymphoma

PURPOSE The value of intensity-modulated radiotherapy (IMRT) for early-stage nasal NK/T-cell lymphoma has not been previously reported. The aim of the present study was to assess the dosimetric parameters, toxicity, and treatment outcomes of patients with nasal NK/T-cell lymphoma. METHODS AND MATERIALS Between 2003 and 2008, 42 patients with early-stage nasal NK/T-cell lymphoma underwent definitive high-dose and extended involved-field IMRT with or without combination chemotherapy. The median radiation dose to the primary tumor was 50 Gy. The dose-volume histograms of the target volume and critical normal structures were evaluated in all patients. The locoregional control, overall survival, and progression-free survival were calculated using the Kaplan-Meier method. RESULTS The average mean dose delivered to the planning target volume was 55.5 Gy. Only 1.3% and 2.5% of the planning target volume received <90% and 95% of the prescribed dose, respectively, indicating excellent planning target volume coverage. The mean dose and average dose to the parotid glands was 15 Gy and 14 Gy, respectively. With a median follow-up time of 27 months, the 2-year locoregional control, overall survival, and progression-free survivalrate was 93%, 78%, and 74%, respectively. No Grade 4 or 5 acute or late toxicity was reported. CONCLUSIONS High-dose and extended involved-field IMRT for patients with early-stage nasal NK/T-cell lymphoma showed favorable locoregional control, overall survival, and progression-free survival, with mild toxicity. The dose constraints of IMRT for the parotid glands can be limited to <20 Gy in these patients.

Failure patterns and clinical implications in early stage nasal natural killer/T-cell lymphoma treated with primary radiotherapy.

This study aimed to evaluate the failure patterns and clinical implications in patients with early stage nasal natural killer (NK)/T‐cell lymphoma treated with primary radiotherapy.

Immunophenotypic characteristics and clinical relevance of CD56+ and CD56− extranodal nasal-type natural killer/T-cell lymphoma

This study aimed to determine whether the phenotypic characteristics of the two subtypes of CD56+ and CD56− lymphoma have relevance for their clinical behavior and prognosis. The immunophenotypes of all patients were confirmed using standard criteria for CD20, CD3ε, CD56, cytotoxic molecules (T-cell intracellular antigen-1 [TIA-1] and granzyme B), and Ki-67, and in situ hybridization for Epstein–Barr virus (EBV)-encoded RNA (EBER). CD56 was expressed in 90 of 118 (76.3%) patients. The majority (83.3%) of patients with nasal natural killer/T-cell lymphoma (NKTCL) presented with CD56+ lymphoma, whereas patients with NKTCL of the extranasal upper aerodigestive tract were more likely to have CD56− lymphoma (53.6%, p < 0.000). A lower percentage of expression of granzyme B and Ki-67 (>50%) was found in patients with CD56− lymphoma compared with those with CD56+ lymphoma (p < 0.05). The clinical characteristics and prognosis were comparable between patients with CD56+ and CD56− lymphomas. The corresponding overall survival and progression-free survival rates were 74.1% and 56.7%, respectively, for patients with CD56+ lymphoma compared with 81.6% and 60.5% for those with CD56− lymphoma (p > 0.05). There was no clinical or prognostic significance in determining the two subtypes of CD56+ and CD56− NKTCL based on their immunophenotypic profiles, which has clinical implications for pathological diagnosis and insight into disease behavior.

Immunophenotypic and clinical differences between the nasal and extranasal subtypes of upper aerodigestive tract natural killer/T-cell lymphoma.

PURPOSE To investigate, in a large cohort of patients, the immunophenotypic and clinical differences of nasal and extranasal extranodal nasal-type natural killer/T-cell lymphoma of the upper aerodigestive tract (UADT-NKTCL) and examine the relevance of the immunophenotype on the clinical behavior, prognosis, and treatment. METHODS AND MATERIALS A total of 231 patients with UADT-NKTCL were recruited. One hundred eighty-one patients had primary location in the nasal cavity (nasal UADT-NKTCL), and 50 patients had primary extranasal UADT-NKTCL. RESULTS Patients with extranasal UADT-NKTCL had more adverse clinical features, including advanced-stage disease, regional lymph node involvement, B symptoms, and poor performance status, than patients with nasal UADT-NKTCL. In addition, CD56 and granzyme B were less frequently expressed in extranasal UADT-NKTCL. The 5-year overall survival rate was 74.1% for the entire group and 76.0% for early-stage disease. The 5-year overall survival rate for extranasal UADT-NKTCL was similar or superior to that of nasal UADT-NKTCL for all disease stages (76.9% vs 73.4%, P=.465), stage I disease (75.9% vs 79.2%, P=.786), and stage II disease (83.3% vs 50.3%, P=.018). CD56 expression and a Ki-67 proliferation rate ≥ 50% predicted poorer survival for extranasal UADT-NKTCL but not for nasal UADT-NKTCL. CONCLUSIONS Patients with nasal and extranasal UADT-NKTCL have significantly different clinical features, immunophenotypes, and prognosis. Extranasal UADT-NKTCL should be considered as a distinct subgroup apart from the most commonly diagnosed prototype of nasal UADT-NKTCL.

Favorable outcome with doxorubicin-based chemotherapy and radiotherapy for adult patients with early stage primary systemic anaplastic large-cell lymphoma

The aim of this study was to analyze outcomes in adult patients with early stage systemic anaplastic large‐cell lymphoma (ALCL) treated with doxorubicin‐based chemotherapy and radiotherapy. Forty‐six adult patients with early stage systemic ALCL received chemotherapy followed by radiotherapy. All patients except two received chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or a CHOP‐like regimen. Twenty patients had stage I disease, and 26 patients had stage II disease. The 5‐yr overall survival (OS), progression‐free survival (PFS), and local control rates for all patients were 84.4%, 63.6%, and 90.8%, respectively. The 5‐yr OS and PFS rates were 95.0% and 77.4% for Ann Arbor stage I disease, and 75.1% and 51.7% for stage II disease, respectively. Lymph node involvement was the main pattern of disease progression or relapse for these patients. Adult patients with early stage systemic ALCL treated with doxorubicin‐based chemotherapy and radiotherapy had a favorable prognosis.