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.

Clinical Characteristics and Long-Term Outcomes following Surgery Combined with Adjuvant Radiotherapy for Patients with Frontal Sinus Malignancies.

Objectives Primary frontal sinus malignancies (FSMs) are the rarest sinonasal cancers. This study aimed to determine clinicopathologic characteristics of primary FSMs and provide long-term survival outcomes. Design This study is a retrospective review. Setting The study was conducted at a tertiary medical center. Participants Patients who participated in this study were diagnosed with primary FSMs. Main Outcome Measures Median survival time is the primary outcome measure of this study. Results In this series, the median age was 48 years (30-53 years) and all patients were male. There were five cases with squamous cell carcinoma and one with osteosarcoma. All cases presented with locally advanced disease without regional lymphatic metastasis, including five cases of stage III and one case of stage II. The two most common pathways of tumor invasion were as follows: local tumor broke posteriorly through bone wall and invaded dura mater, followed by frontal lobe; local tumor infiltrated downward through the floor of frontal sinus into ethmoid sinus, thereafter invaded laterally orbit and orbital contents. All patients received surgery followed by postoperative radiotherapy at the total doses of 50 to 75.95 Gy. Among them, only one patient underwent R0 resection, the rest of patients underwent R1/R2 resection. With a median survival time of 56 months (32-76 months), two patients receiving R1/R2 resection developed treatment failure and died within 5 years, including one case with local recurrence and one with local recurrence, thereafter distant metastasis. Conclusion The majority of FSMs presented with peripherally invasive progression lesions which led to a high ratio of R1/R2 resection. Surgery combined with postoperative radiotherapy might result in satisfactory efficacy.

Cerebral functional abnormalities in patients with nasopharyngeal carcinoma after radiotherapy: an observational magnetic resonance resting-state study.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is sensitive to radiotherapy (RT). However, neurocognitive complications such as memory loss and learning and attention deficits emerge in the survivors of NPC who received RT. It remains unclear how radiation affects patient brain function. This pilot study aimed at finding cerebral functional alterations in NPC patients who have received RT. METHODS: From September 2014 to December 2016, 42 individuals, including 22 NPC patients and 20 normal volunteer controls in National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College, were recruited in this study. All patients received resting-state functional magnetic resonance imaging scans and neurocognitive tests 1 day before the initiation of RT (baseline) and 1 day after the completion of RT; the 20 normal controls were also subjected to the same scans and tests. The amplitude of the low-frequency fluctuations (ALFF) in blood oxygen level-dependent signals and functional connectivity (FC) were used to characterize cerebral functional changes. Independent t test, paired t test, and analysis of variances were used to obtain statistical significance across groups. RESULTS: After RT, NPC patients showed significantly decreased ALFF values in the calcarine sulcus, lingual gyrus, cuneus, and superior occipital gyrus and showed significantly reduced FC mainly in the default mode network (P < 0.05, corrected by AlphaSim). Relative to the controls, ALFF was decreased in the lingual gyrus, calcarine sulcus, cingulate cortex, medial prefrontal gyrus (P < 0.05, corrected by AlphaSim), and FC reduction was found in multiple cerebellar-cerebral regions, including the cerebellum, parahippocampus, hippocampus, fusiform gyrus, inferior frontal gyrus, inferior occipital gyrus, precuneus, and cingulate cortex (P < 0.001, corrected by AlphaSim). CONCLUSIONS: Cerebral functional alterations occur immediately after RT. This study may provide an explanation for the cognitive deficits in the morphologically normal-appearing brains of NPC patients after RT and may contribute to the understanding of the complex mechanism of RT.

Patterns of Primary Tumor Invasion and Regional Lymph Node Spread Based on Magnetic Resonance Imaging in Early-Stage Nasal NK/T-cell Lymphoma: Implications for Clinical Target Volume Definition and Prognostic Significance.

PURPOSE: This study aimed to determine the pathways of primary tumor invasion (PTI) and regional lymph node (LN) spread based on magnetic resonance imaging (MRI) in early-stage nasal NK/T-cell lymphoma (NKTCL), to improve clinical target volume (CTV) delineation and evaluate the prognostic value of locoregional extension patterns. METHODS AND MATERIALS: A total of 105 patients with newly diagnosed early-stage nasal NKTCL who underwent pretreatment MRI were retrospectively reviewed. All patients received radiation therapy with or without chemotherapy. RESULTS: The incidences of PTI and regional LN involvement were 64.7% and 25.7%, respectively. Based on the incidence of PTI, involved sites surrounding the nasal cavity were classified into 3 risk subgroups: high-risk (>20%), intermediate-risk (5%-20%), and low-risk (<5%). The most frequently involved site was the nasopharynx (35.2%), followed by the maxillary (21.9%) and ethmoid (21.9%) sinuses. Local disease and regional LN spread followed an orderly pattern without LN skipping. The retropharyngeal nodes (RPNs) were most frequently involved (19.0%), followed by level II (11.4%). The 5-year overall survival (OS), progression-free survival (PFS), and locoregional control (LRC) rates for all patients were 72.8%, 65.2%, and 90.0%, respectively. The presence of PTI and regional LN involvement based on MRI significantly and negatively affected PFS and OS. CONCLUSIONS: Early-stage nasal NKTCL presents with a high incidence of PTI but a relatively low incidence of regional LN spread. Locoregional spread followed an orderly pattern, and PTI and regional LN spread are powerful prognostic factors for poorer survival outcomes. CTV reduction may be feasible for selected patients.

Clinical disparity and favorable prognoses for patients with Waldeyer ring extranodal nasal-type NK/T-cell lymphoma and diffuse large B-cell lymphoma.

OBJECTIVES: This study aimed to compare the clinical characteristics and prognosis of Waldeyer ring extranodal nasal-type natural killer (NK)/T-cell lymphoma (WR-NKTCL) and Waldeyer ring diffuse large B-cell lymphoma (WR-DLBCL). METHODS: Consecutive diagnoses of 122 WR-DLBCL and 44 WR-NKTCL patients, receiving mainly primary radiotherapy in early-stage WR-NKTCL and primary chemotherapy in early-stage WR-DLBCL, were reviewed. RESULTS: WR-NKTCL occurred predominately in young males, as nasopharyngeal stage I disease with B-symptoms, extranodal dissemination, and involving adjacent structures. WR-DLBCL was mainly stage II tonsillar disease with regional lymph node involvement. The 5-year overall survival (OS) and progression-free survival (PFS) rates were 74% and 67% in WR-DLBCL, respectively, and 68% (P=0.468) and 59% (P=0.303) in WR-NKTCL. In stages I and II disease, WR-DLBCL 5-year OS and PFS were 79% and 76% compared with 72% (P=0.273) and 62% (P=0.117) in WR-NKTCL. In stage I disease, WR-DLBCL 5-year OS and PFS were 81% and 81%, compared with 76% (P=0.394) and 63% (P=0.236) in WR-NKTCL. In addition, the prognostic factors and failure patterns in WR-DLBCL and WR-NKTCL differed substantially. CONCLUSIONS: These results indicate that remarkable clinical disparities exist between WR-DLBCL and WR-NKTCL; however, different treatment strategies for each can result in similarly favorable prognoses.

Dosimetric and clinical outcomes of involved-field intensity-modulated radiotherapy after chemotherapy for early-stage Hodgkin's lymphoma with mediastinal involvement.

PURPOSE: To evaluate the dosimetric and clinical outcomes of involved-field intensity-modulated radiotherapy (IF-IMRT) for patients with early-stage Hodgkin's lymphoma (HL) with mediastinal involvement. METHODS AND MATERIALS: Fifty-two patients with early-stage HL that involved the mediastinum were reviewed. Eight patients had Stage I disease, and 44 patients had Stage II disease. Twenty-three patients (44%) presented with a bulky mediastinum, whereas 42 patients (81%) had involvement of both the mediastinum and either cervical or axillary nodes. All patients received combination chemotherapy followed by IF-IMRT. The prescribed radiation dose was 30-40 Gy. The dose-volume histograms of the target volume and critical normal structures were evaluated. RESULTS: The median mean dose to the primary involved regions (planning target volume, PTV1) and boost area (PTV2) was 37.5 Gy and 42.1 Gy, respectively. Only 0.4% and 1.3% of the PTV1 and 0.1% and 0.5% of the PTV2 received less than 90% and 95% of the prescribed dose, indicating excellent PTV coverage. The median mean lung dose and V20 to the lungs were 13.8 Gy and 25.9%, respectively. The 3-year overall survival, local control, and progression-free survival rates were 100%, 97.9%, and 96%, respectively. No Grade 4 or 5 acute or late toxicities were reported. CONCLUSIONS: Despite the large target volume, IF-IMRT gave excellent dose coverage and a favorable prognosis, with mild toxicity in patients with early-stage mediastinal HL.

The extent of cutaneous lesions predicts outcome in extranodal nasal-type natural killer/T-cell lymphoma of the upper aerodigestive tract with secondary cutaneous involvement.

This study determined the clinical characteristics and prognosis for patients with extranodal nasal-type natural killer/T-cell lymphoma (NKTCL) with secondary cutaneous involvement. Twenty-eight patients with NKTCL of the upper aerodigestive tract with secondary cutaneous involvement were reviewed. The median overall survival (OS) was 21.5 months from the first diagnosis, and 12.3 months from the presentation of a cutaneous lesion. The 5-year OS rate was 43.1% (median, 28 months) for patients with localized cutaneous disease compared with 0% (median, 3.6 months) for generalized cutaneous disease (p = 0.017). The 2-year OS rates were 67.5% for patients who achieved a complete response (CR) compared with 19.4% (median, 5.2 months) for patients who did not (p = 0.003). Patients with NKTCL with secondary cutaneous dissemination overall have a poor prognosis, but a relatively favorable prognosis was identified for the small subgroup of patients who had localized cutaneous lesions and achieved a CR.