"Moderate" adjuvant chemotherapy-induced leukopenia is beneficial for survival of patients with early breast cancer: a retrospective study.

BACKGROUND: The association between chemotherapy-induced leukopenia (CIL) and survival for patients with early breast cancer (EBC) is not known. We investigated the relationship between different grades of CIL and survival in patients with EBC receiving adjuvant chemotherapy. METHODS: A total of 442 patients with EBC receiving a regimen containing an anthracycline (A) and taxane (T) were included into our analysis. Survival analyses were undertaken using Kaplan-Meier curves. The P-value was calculated using the log rank test. Subgroup analysis was conducted to investigate the correlation of CIL grade and survival based on the clinicopathological characteristics of patients. Afterwards, univariate and multivariate analyses screened out independent prognostic factors to construct a prognostic model, the robustness of which was verified. RESULTS: Patients with EBC who experienced grade 2-4 ("moderate" and "severe") CIL were associated with longer overall survival (OS) than those with grade 0-1 (mild) CIL (P = 0.021). Compared with patients with mild CIL, OS was longer in patients with severe CIL (P = 0.029). Patients who suffered from moderate CIL tended to have longer OS than those with mild CIL (P = 0.082). Nevertheless, there was no distinguishable difference in OS between moderate- or severe-CIL groups. Subgroup analysis revealed that patients with moderate CIL had longer OS than those with mild CIL among patients who were premenstrual, or with human epidermal growth factor receptor 2-positive (HER2+), > 3 lymph nodes with metastases, a tumor diameter > 5 cm. A prognostic model based on menstrual status, N stage, and CIL grade showed satisfactory robustness. CONCLUSION: The grade of CIL was strongly associated with the prognosis among patients with EBC who received a regimen containing both anthracyclines and taxanes. Patients with a "moderate" CIL grade tended to have better survival outcomes.

Effect of Capecitabine Maintenance Therapy Using Lower Dosage and Higher Frequency vs Observation on Disease-Free Survival Among Patients With Early-Stage Triple-Negative Breast Cancer Who Had Received Standard Treatment: The SYSUCC-001 Randomized Clinical Trial.

Importance: Among all subtypes of breast cancer, triple-negative breast cancer has a relatively high relapse rate and poor outcome after standard treatment. Effective strategies to reduce the risk of relapse and death are needed. Objective: To evaluate the efficacy and adverse effects of low-dose capecitabine maintenance after standard adjuvant chemotherapy in early-stage triple-negative breast cancer. Design, Setting, and Participants: Randomized clinical trial conducted at 13 academic centers and clinical sites in China from April 2010 to December 2016 and final date of follow-up was April 30, 2020. Patients (n = 443) had early-stage triple-negative breast cancer and had completed standard adjuvant chemotherapy. Interventions: Eligible patients were randomized 1:1 to receive capecitabine (n = 222) at a dose of 650 mg/m2 twice a day by mouth for 1 year without interruption or to observation (n = 221) after completion of standard adjuvant chemotherapy. Main Outcomes and Measures: The primary end point was disease-free survival. Secondary end points included distant disease-free survival, overall survival, locoregional recurrence-free survival, and adverse events. Results: Among 443 women who were randomized, 434 were included in the full analysis set (mean [SD] age, 46 [9.9] years; T1/T2 stage, 93.1%; node-negative, 61.8%) (98.0% completed the trial). After a median follow-up of 61 months (interquartile range, 44-82), 94 events were observed, including 38 events (37 recurrences and 32 deaths) in the capecitabine group and 56 events (56 recurrences and 40 deaths) in the observation group. The estimated 5-year disease-free survival was 82.8% in the capecitabine group and 73.0% in the observation group (hazard ratio [HR] for risk of recurrence or death, 0.64 [95% CI, 0.42-0.95]; P = .03). In the capecitabine group vs the observation group, the estimated 5-year distant disease-free survival was 85.8% vs 75.8% (HR for risk of distant metastasis or death, 0.60 [95% CI, 0.38-0.92]; P = .02), the estimated 5-year overall survival was 85.5% vs 81.3% (HR for risk of death, 0.75 [95% CI, 0.47-1.19]; P = .22), and the estimated 5-year locoregional recurrence-free survival was 85.0% vs 80.8% (HR for risk of locoregional recurrence or death, 0.72 [95% CI, 0.46-1.13]; P = .15). The most common capecitabine-related adverse event was hand-foot syndrome (45.2%), with 7.7% of patients experiencing a grade 3 event. Conclusions and Relevance: Among women with early-stage triple-negative breast cancer who received standard adjuvant treatment, low-dose capecitabine maintenance therapy for 1 year, compared with observation, resulted in significantly improved 5-year disease-free survival. Trial Registration: ClinicalTrials.gov Identifier: NCT01112826.

Effect of rituximab on adult Burkitt's lymphoma: a systematic review and meta-analysis.

The treatment of Burkitt's lymphoma with rituximab is controversial, and studies that compared the efficacy of chemotherapy alone with chemotherapy plus rituximab have not been powered to test differences in overall survival (OS). We conducted this systematic review and meta-analysis to identify the value of rituximab for the treatment of BL to guide treatment decisions. Based on the PubMed, Web of Science, and Cochrane library online electronic databases, all retrospective and randomized clinical trial studies that compared the aforementioned two regimens were included. The pooled hazard ratio and odds ratio were analyzed using Review Manager 5.3. The primary outcome was the 2-year OS. A total of 581 publications were identified using a predetermined search strategy. One randomized controlled trial (RCT) and five retrospective studies, which included 646 cases (351 cases for the chemotherapy with rituximab group and 295 cases for the chemotherapy alone group), fulfilled the selection criteria and were included in the meta-analysis. The chemotherapy with rituximab group was associated with a higher 2-year OS (hazard ratio 0.62, 95 % CI 0.45-0.85, P = 0.003), 2-year progression-free survival (hazard ratio 0.46, 95 % CI 0.43-0.50, P < 0. 001), and complete remission rate (odds ratios 3.26, 95 % CI 1.22-8.66, P = 0.02). In addition, the treatment-related mortality did not significantly differ between the two treatment regimens (odds ratio 1.16, 95 % CI 0.55-2.45, P = 0.69). The meta-analysis indicates that the addition of rituximab to the treatment regimen for Burkitt's lymphoma may be associated with a significant survival benefit and did not increase the mortality compared with chemotherapy alone.

Radiotherapy and PGEMOX/GELOX regimen improved prognosis in elderly patients with early-stage extranodal NK/T-cell lymphoma.

The optimal treatment strategy for elderly patients with natural killer/T-cell lymphoma (NKTCL) remains to be established. A total of 63 elderly patients with newly diagnosed NKTCL were retrospectively reviewed. Among the patients with stage I-II disease, 58.3 % received radiotherapy (RT) ± chemotherapy, and 41.7 % received chemotherapy alone. Compared with chemotherapy alone, RT ± chemotherapy elicited a significantly higher overall response rate (ORR) (100 vs. 57.1 %, P < 0.001) and substantially prolonged 5-year overall survival (OS) (55.3 vs. 18.0 %, P < 0.001) in patients with stage I-II disease. Compared with other chemotherapeutic regimens, pegaspargase plus gemcitabine and oxaliplatin (PGEMOX)/L-asparaginase plus gemcitabine and oxaliplatin (GELOX) was associated with a significantly higher ORR (92.9 vs. 51.6 %, P = 0.009) and a significantly improved 5-year OS (78.6 vs. 23.9 %, P = 0.010) in patients with stage I-II disease. Nine patients with stage I-II disease who were treated with PGEMOX/GELOX followed by RT had an encouraging outcome (5-year OS 100 %, 5-year progression-free survival (PFS) 85.7 %), which was superior to that of patients receiving other regimens followed by RT. In conclusion, RT played an important role for elderly patients with early-stage NKTCL, and the PGEMOX/GELOX regimen was superior to other regimens. The combination of them may be a promising treatment option.

The extent of local tumor invasion predicts prognosis in stage IE nasal natural killer/T-cell lymphoma: a novel T staging system for risk stratification.

A heterogeneous treatment response and prognosis exists among patients with Ann Arbor stage IE natural killer/T-cell lymphoma (NKTCL), and further risk stratification is required to identify high-risk patients. Here, we assessed the extent of local tumor invasion (LTI) in 185 patients with Ann Arbor stage IE primary nasal NKTCL and proposed a novel four-level T staging system. We found that a more advanced T stage was associated with a significantly lower rate of complete remission (CR) after chemotherapy and a marginally lower rate of CR after radiotherapy. While patients with no LTI (T1) or mild LTI (T2) presented with similar 5-year overall survival (OS; 83.6 % vs. 86.0 %, P = 0.990), those with moderately or highly advanced local disease (T3 or T4) had significantly worse survival (5-year OS was 63.3 % and 35.1 %, respectively). A more advanced T stage (T3 or T4) was an independent prognostic factor for both OS and progression-free survival (PFS) in the Cox regression model. In addition, patients with T3 or T4 disease experienced locoregional failure more frequently than those with T1 or T2 disease, and patients with T4 disease had a significantly higher risk of distant failure. Our data demonstrated that the T staging system, based on the extent of LTI, could serve as an effective clinical parameter for further risk stratification among patients with primary nasal Ann Arbor stage IE NKTCL.

Treatment outcome of patients with advanced stage natural killer/T-cell lymphoma: elucidating the effects of asparaginase and postchemotherapeutic radiotherapy.

The prognosis of advanced stage natural killer/T-cell lymphoma (NKTCL) remains relatively disappointing, and the optimal treatment strategy for this disease has yet to be discovered. Seventy-three patients with Ann Arbor stage III or IV NKTCL were retrospectively reviewed. The treatment efficacies of asparaginase-containing and asparaginase-absent chemotherapy regimens were compared, and the effects of postchemotherapeutic radiotherapy were explored. The overall response rate (ORR) of the asparaginase-containing regimens was marginally higher than that of the asparaginase-absent regimens (56.5 vs 32.6 %, P = 0.057). However, no significant difference was observed in 2-year overall survival (OS) (38.3 vs 22.7 %, P = 0.418) or 2-year progression-free survival (PFS) (25.4 vs 14.9 %, P = 0.134) between the asparaginase-containing and asparaginase-absent groups. Postchemotherapeutic radiotherapy was associated with a significantly prolonged survival (2-year OS 57.5 vs 14.5 %, P < 0.001; 2-year PFS 46.3 vs 8.4 %, P < 0.001) and was an independent predictor of both OS and PFS. Radiotherapy significantly improved the prognosis among the patients who exhibited complete or partial remission after initial chemotherapy (2-year OS 81.5 vs 40.2 %, P = 0.002; 2-year PFS 65.6 vs 23.4 %, P = 0.008) but failed to provide a significant survival advantage among those who experienced stable or progressive disease after initial chemotherapy. In conclusion, the use of asparaginase did not significantly improve survival for the treatment of patients with stage III/IV NKTCL. Postchemotherapeutic radiotherapy provided additional prognostic benefits to patients who responded well to the initial chemotherapy, which requires further validation in future prospective studies using larger sample sizes.

Does the Dose of Standard Adjuvant Chemotherapy Affect the Triple-negative Breast Cancer Benefit from Extended Capecitabine Metronomic Therapy? An Exploratory Analysis of the SYSUCC-001 Trial.

Purpose: Results from studies of extended capecitabine after the standard adjuvant chemotherapy in early stage triple-negative breast cancer (TNBC) were inconsistent, and only low-dose capecitabine from the SYSUCC-001 trial improved disease-free survival (DFS). Adjustment of the conventional adjuvant chemotherapy doses affect the prognosis and may affect the efficacy of subsequent treatments. This study investigated whether the survival benefit of the SYSUCC-001 trial was affected by dose adjustment of the standard adjuvant chemotherapy or not. Patients and Methods: We reviewed the adjuvant chemotherapy regimens before the extended capecitabine in the SYSUCC-001 trial. Patients were classified into "consistent" (standard acceptable dose) and "inconsistent" (doses lower than acceptable dose) dose based on the minimum acceptable dose range in the landmark clinical trials. Cox proportional hazards model was used to investigate the impact of dose on the survival outcomes. Results: All 434 patients in SYSUCC-001 trial were enrolled in this study. Most of patients administered the anthracycline-taxane regimen accounted for 88.94%. Among patients in the "inconsistent" dose, 60.8% and 47% received lower doses of anthracycline and taxane separately. In the observation group, the "inconsistent" dose of anthracycline and taxane did not affect DFS compared with the "consistent" dose. Moreover, in the capecitabine group, the "inconsistent" anthracycline dose did not affect DFS compared with the "consistent" dose. However, patients with "consistent" taxane doses benefited significantly from extended capecitabine (P=0.014). The sufficient dose of adjuvant taxane had a positive effect of extended capecitabine (hazard ratio [HR] 2.04; 95% confidence interval [CI] 1.02 to 4.06). Conclusion: This study found the dose reduction of adjuvant taxane might negatively impact the efficacy of capecitabine. Therefore, the reduction of anthracycline dose over paclitaxel should be given priority during conventional adjuvant chemotherapy, if patients need dose reduction and plan for extended capecitabine.

Survival advantage of locoregional and systemic therapy in oligometastatic breast cancer: an international retrospective cohort study (OLIGO-BC1).

BACKGROUND: An international retrospective cohort study was conducted to clarify the survival advantage of combination therapy with locoregional and systemic therapy (ST) in oligometastatic breast cancer (BC). METHODS: Patients with oligometastatic BC diagnosed from 2007 to 2012 were enrolled in center hospitals in China, Korea and Japan. It was defined as a low-volume metastatic disease at up to five sites and not necessarily in the same organ. Cases with brain, pleural, peritoneal and pericardial metastases were excluded. The primary endpoint was overall survival (OS) from the initial diagnosis of oligometastases. OS was summarized using the Kaplan-Meier method. A multivariable Cox regression model was used to estimate the hazard ratio (HR) for clinicopathological factors. RESULTS: Among 1,295 cases registered from February 2018 to May 2019, 932 remained for analysis after the exclusion of unavailable cases and locoregional recurrence. One metastatic site was found in 400 cases, 2 in 243, 3 in 130, 4 in 86 and 5 in 73. At the median follow-up of 4.5 years, 5-year OS was 54.7% and 39.7% for 321 cases in the combination therapy group and 611 cases in the ST group, respectively. An adjusted HR was 0.66 (95% confidence interval: 0.55, 0.79). Some types of ST without chemotherapy alone, younger age, ECOG performance status 0, early-stage BC, non-triple negative subtype, fewer metastatic sites and longer duration of surgery to relapse were significantly favorable prognostic factors. CONCLUSION: Combination therapy may be considered for longer survival under some conditions in oligometastatic BC.

Novel Signatures Based on the Lymphocyte-to-C-Reactive Protein Ratio Predict the Prognosis of Patients with Early Breast Cancer: A Retrospective Study.

Background: The value of the lymphocyte-to-C-reactive protein (CRP) ratio (LCR) in early breast cancer (BC) is unclear. We explored the correlation between the LCR and survival of patients with early BC and established effective LCR-based prognostic signatures for predicting prognosis. Methods: In this retrospective study, we randomized 623 patients with early-stage BC diagnosed in December 2010 to October 2012 at the Sun Yat-sen University Cancer Center to training and verification datasets. The median follow-up of all patients was 109 months. The survival differences were calculated by Kaplan-Meier method using the Log rank test. For overall survival (OS) and disease-free survival (DFS), the independent factors in the training dataset were identified using univariate and multivariate Cox analyses, in which two-tailed P-values < 0.05 were considered statistically significant. Based on this, we respectively constructed novel signatures for survival prediction and validated the efficiency of signatures through the concordance index (C-index), calibration and receiver operating characteristic (ROC) curves in both datasets. Results: The LCR, lymphatic vessel invasion (LVI), progesterone receptor (PR) status, and Ki67 index were independent prognostic factors of OS. And the LCR and LVI are associated to DFS too. High LCR was associated with better OS and DFS. We constructed the prediction signatures based on those independent prognostic factors and calculated the risk scores. Patients in the training dataset with higher risk scores had significantly worse prognosis (P < 0.001). The signature had excellent discrimination capacity, with an OS C-index of 0.785 [95% confidence interval (CI): 0.713-0.857] and 0.750 (95% CI: 0.669-0.832) in the training and verification datasets, respectively. The time-ROC curves also suggest accurate prediction by the signature. Conclusion: The LCR was a significant prognostic predictor of OS and DFS in early BC. The LCR-based prognostic signatures could be a useful tool for individualized therapeutic guidance.

Trastuzumab Plus Endocrine Therapy or Chemotherapy as First-line Treatment for Patients with Hormone Receptor-Positive and HER2-Positive Metastatic Breast Cancer (SYSUCC-002).

PURPOSE: There is no research evidence demonstrate which is the better partner strategy, endocrine therapy or chemotherapy, to combine with anti-HER2 therapy as the first-line management of hormone receptor (HR)-positive (HR+) and HER2-positive (HER2+) metastatic breast cancer (MBC). We wished to ascertain if trastuzumab plus endocrine therapy is noninferior to trastuzumab plus chemotherapy. PATIENTS AND METHODS: We conducted an open-label, noninferiority, phase III, randomized, controlled trial (NCT01950182) at nine hospitals in China. Participants, stratified by previous adjuvant endocrine therapy and disease status (recurrent disease vs. de novo metastasis), were assigned randomly (1:1) to receive trastuzumab plus endocrine therapy (per investigator's choice of oestrogen-receptor modulators or aromatase inhibitor, with/without concurrent ovarian suppression) or chemotherapy (per investigator's choice of taxanes, capecitabine, or vinorelbine). The primary endpoint was progression-free survival (PFS) with a noninferiority upper margin of 1.35 for the HR. The intention-to-treat population was used in primary and safety analyses. RESULTS: A total of 392 patients were enrolled and assigned randomly to receive trastuzumab plus endocrine therapy (ET group, n = 196) or trastuzumab plus chemotherapy (CT group, n = 196). After a median follow-up of 30.2 months [interquartile range (IQR) 15.0-44.7], the median PFS was 19.2 months [95% confidence interval (CI), 16.7-21.7)] in the ET group and 14.8 months (12.8-16.8) in the CT group (hazard ratio, 0.88; 95% CI, 0.71-1.09; Pnoninferiority < 0.0001). A significantly higher prevalence of toxicity was observed in the CT group compared with the ET group. CONCLUSIONS: Trastuzumab plus endocrine therapy was noninferior to trastuzumab plus chemotherapy in patients with HR+HER2+ MBC.

Establishment and Validation of Nomogram Based on Combination of Pretreatment C-Reactive Protein/Albumin Ratio-EBV DNA Grade in Nasopharyngeal Carcinoma Patients Who Received Concurrent Chemoradiotherapy.

BACKGROUND: A higher ratio of pretreatment C-reactive protein/albumin ratio (CAR) is associated with poor prognosis in nasopharyngeal carcinoma (NPC), and Epstein-Barr virus (EBV) DNA level is known to not only participate in the occurrence of nasopharyngeal carcinoma but also affect the development and prognosis of the disease. Herein, we proposed that a combination of both these markers could improve the predictive prognostic ability. METHODS: In all, 842 NPC patients who received concurrent chemoradiotherapy (CCRT) were entered in this study. We collected all patients' blood samples and EBV DNA copy numbers within one week before any treatment. Receiver operating characteristic (ROC) curve was used to determine the optimal cut-off. We employed the Kaplan-Meier method for survival analyses and the univariate and multivariate analyses (Cox proportional hazards regression model) for statistical analysis. A nomogram was constructed based on multivariate analyses results of the validation set. The model was internally validated using 1000 bootstrap samples to avoid overfitting. Another validation of 10-fold cross-validation was also applied. Calibration curves and concordance index (C-index) were calculated to determine predictive and discriminatory capacity. RESULTS: In the whole cohort, we observed that higher CAR, EBV DNA level, and CAR-EBV DNA (C-E) grade were associated with shorter overall survival (OS) and distant metastasis-free survival (DMFS) (all P<0.05). In univariate and multivariate analyses, C-E grade was an independent prognostic factor (all P<0.05). In the training set, we gained the similar results with the whole set. According to multivariate analyses of the training set, we constructed a nomogram. The results of bootstrap samples and 10-fold cross-validation showed favorable predictive efficacy. And calibration curves of the model provided credibility to its predictive capability. CONCLUSION: C-E grade was confirmed as an independent prognostic predictor in patients with NPC who received CCRT. Higher level of pretreatment C-E grade could signify a higher risk of metastasis and shorter OS. The prognostic nomogram based on C-E grade was dependable in nasopharyngeal carcinoma patients.

Prognostic significance of the Controlling Nutritional Status (CONUT) score in surgically treated breast cancer patients.

BACKGROUND: Breast cancer is one of the most common malignancy in women with high mortality rate. Given the growing evidence shows that immune-inflammatory system influences the survival of patients with cancer, we assessed the prognostic significance of the preoperative Controlling Nutritional Status (CONUT) score in patients with breast cancer who underwent surgery. METHODS: We conducted a retrospective analysis of 1,367 breast cancer patients who underwent surgery between December 2010 and October 2012. All individual preoperative serum albumin concentration, total cholesterol concentration, and total peripheral lymphocyte count were counted to calculate CONUT. Higher CONUT score is in line with worse nutritional status. The optimal cut-off of CONUT score was set at 3 to categorize the investigated patients into two groups, namely a high- or low-CONUT score group. We adopted univariate and multivariate analyses (Cox proportional hazards regression model) statistical method. RESULTS: Patients in the high-CONUT score group had shorter overall survival (OS) and recurrence-free survival (RFS) in comparison with those in the low-CONUT score group, 66.43 vs. 69.30 months and 54.70 vs. 59.98 months respectively (all P value <0.05). Univariate and multivariate analyses revealed that the CONUT score was an independent predictor of OS (P=0.029 and 0.046, respectively) and RFS (P=0.001, P=0.013, respectively). CONCLUSIONS: The CONUT score was identified as an independent prognostic indicator in surgically treated breast cancer patients, indicating that, compared with the low CONUT score, a high CONUT score may lead to poorer prognosis.

The Prognostic Prediction Value of Systemic Inflammation Score and the Development of a Nomogram for Patients With Surgically Treated Breast Cancer.

Background: Systemic inflammation score (SIS) has been verified as a novel prognostic indicator in several cancer types. However, its prognostic value in breast cancer remains unknown. Furthermore, a nomogram based on SIS is yet to be constructed for breast cancer. We conducted this study to explore the association between SIS and prognosis of breast cancer, and to construct a good prognostic nomogram model. Methods: A total of 1,180 breast cancer patients who underwent curative surgery between December 2010 and January 2013 were recruited. They were randomly assigned to the training set (n = 944) or the validation set (n = 236). All patient blood samples were collected within 1 week prior to operation. According to previous reports, SIS was calculated for all patients, who were then classified into two groups: high-SIS and low-SIS. The Kaplan-Meier method was employed for survival analyses, and univariate and multivariate analyses (Cox proportional hazards regression model) were used for prognostic assessment. A nomogram was constructed based on the results of multivariate analysis. Calibration curves and concordance index (C-index) were compiled to determine predictive and discriminatory capacity. Results: In the training set, the median follow-up time was 6.07 years. Patients in the high-SIS group had an average OS time of 68.05 months, which is shorter than that of the low-SIS group (72.87 months; P = 0.033). Patients in the high-SIS group had average RFS and DMFS times of 56.04 and 54.46 months, respectively, which are shorter than those of the low-SIS group (60.85 and 59.47 months, respectively; P = 0.247 and P = 0.032). Univariate and multivariate analyses revealed SIS to be an independent prognostic factor for OS and DMFS time. The nomogram for the training set indicated OS and DMFS C-indexes of 0.794 (95% CI, 0.772-0.816) and 0.712 (95% CI, 0.684-0.740), respectively. In the validation set, the OS and DMFS C-indexes were 0.889 (95% CI, 0.845-0.933) and 0.696 (95%. CI, 0.611-0.781), respectively. Conclusions: SIS was confirmed as an independent prognostic predictor among patients with breast cancer who had undergone surgery with curative intent. Higher preoperative SIS may indicate higher risk of metastasis and shorter overall survival time. The prognostic nomogram based on SIS was dependable for breast cancer patients who underwent curative surgery.

Expression of PD-L1 on Monocytes Is a Novel Predictor of Prognosis in Natural Killer/T-Cell Lymphoma.

Background: Natural killer/T-cell lymphoma (NKTCL) is a highly aggressive lymphoma with a dismal prognosis, and novel therapeutic targets are urgently needed. Programmed death-ligand 1 (PD-L1) has become a promising therapeutic target for various cancers, but most of the studies have focused on expression of PD-L1 on tumor cells. Expression of PD-L1 on tumor-infiltrating non-malignant cells, especially monocytes, has not been studied in NKTCL, and its prognostic value remains unknown. Materials and Methods: Expression of PD-L1 on tumor-infiltrating stromal cells was measured in NKTert and HS5 cells when cultured alone or co-cultured with NKTCL cell lines. Clinical samples were collected from 42 patients with newly diagnosed NKTCL. Expression of PD-L1 on monocytes was analyzed in patients' peripheral blood and tumor tissues using flow cytometry and immunofluorescent staining, respectively. Survival data were retrospectively collected and the prognostic significance of PD-L1 expression on monocytes was analyzed. Results: PD-L1 expression on tumor-infiltrating stromal cells was remarkably elevated when co-cultured with NKTCL cells. The percentage of PD-L1+ monocytes among all monocytes in peripheral blood was significantly higher in NKTCL patients than that in healthy individuals. Among NKTCL patients, percentage of PD-L1+ monocytes in blood positively correlated with that in tumor tissues. Patients with a higher percentage (≥78.2%) of PD-L1+ monocytes in blood or with a higher percentage (≥24.2%) of PD-L1+ monocytes in tumor tissues exhibited a significantly inferior survival, compared with their counterparts. A higher percentage of PD-L1+ monocytes in blood or tumor tissues was an independent adverse prognostic factor. Conclusions: Expression of PD-L1 on monocytes is up-regulated and has significant prognostic value in patients with NKTCL.

Characteristics, Prognostic Factors, and Survival of Patients with NK/T-Cell Lymphoma of Non-upper Aerodigestive Tract: A 17-Year Single-Center Experience.

PURPOSE: The extranodal natural killer (NK)/T-cell lymphoma (NKTCL) of non-upper aerodigestive tract (NUAT) was found to have clinical heterogeneity compared with NKTCL of the upper aerodigestive tract (UAT) in small scale studies. We conducted this study in a much larger cohort to analyze the clinical characteristics, prognostic factors, treatment modality, and clinical outcomes of patients with NUAT-NKTCL. MATERIALS AND METHODS: From January 2001 to December 2017, a total of 757 NKTCL patients were identified and included in this study, including 92 NUAT-NKTCL patients (12.2%) and 665 UAT-NKTCL patients (87.8%). RESULTS: NUAT-NKTCL patients had relatively poorer performance status, more unfavorable prognostic factors, and more advanced stage, compared with UAT-NKTCL patients. The 5-year overall survival (OS) was 34.7% for NUAT-NKTCL, which was significantly worse than UAT-NKTCL (64.2%, p<0.001). The median OS duration was 30.9 months for NUAT-NKTCL. Multivariate analysis showed that presence with B symptoms and elevated serum lactate dehydrogenase independently predicted worse OS. International prognostic index score and prognostic index of natural killer lymphoma score still had prognostic values in NUAT-NKTCL, while the Ann Arbor system could not accurately predict the OS. CONCLUSION: NUAT-NKTCL is a distinctive subtype of NKTCL in many aspects. Patients with NUAT-NKTCL have relatively poorer performance status, more unfavorable prognostic factors, more advanced stage, and poorer prognosis.

Trends in survival of patients with stage I/II Burkitt lymphoma in the United States: A SEER database analysis.

The treatment strategy for management of Burkitt lymphoma (BL) has evolved during the past decades and the clinical outcome for this disease as a whole has also improved. Due to limited information reported on survival trends of patients with stage I/II (limited-stage) BL, here we used the Surveillance, Epidemiology, and End Results (SEER) database to conduct our study. The time period was divided into two eras (1983-2001 and 2002-2014) as the recent era reflected more intensive chemotherapy regimens, the availability of rituximab, the widespread use of antiretroviral therapy (ART) and improvements in supportive care. Patients with limited-stage BL had a significantly better 5-year overall survival (OS) in the 2002-2014 era in both univariate analysis and multivariate analysis, compared with those in the 1983-2001 era (64.1% vs 57.4%). However, clinical outcomes of elderly patients (≥60 years) and children patients (0-19 years) did not significantly improve. Older age and race of black were correlated with poorer OS in multivariate analysis, whereas sex, primary sites, and application of radiotherapy did not significantly influence OS. In conclusion, the prognosis of patients with limited-stage BL has improved in the 2002-2014 era, but the outcome was still much poorer in elderly patients, which needs to be improved by identifying newly molecular-targeted drugs and developing novel personalized therapeutic approaches.

Mutation Profiling of Malignant Lymphoma by Next-Generation Sequencing of Circulating Cell-Free DNA.

Background: Malignant lymphomas are a group of distinct lymphoid neoplasms, exhibiting marked diversity in biological behaviors and clinical outcomes. Liquid biopsy, such as circulating cell-free DNA (cfDNA), has recently been attempted to be used for mutation profiling of lymphomas using next-generation sequencing (NGS). However, only limited data about cfDNA are restricted in Hodgkin's lymphoma and B cell lymphoma, and there is no report in the T cell lymphoma so far. Patient and Methods: Medical records of a total of 50 lymphoma patients were retrospectively reviewed, and cfDNA samples were analyzed by capture-based NGS targeting 390 lymphoma- and cancer- relevant genes. We sought to explore the clinical utility of cfDNA in establishing the mutation profiles of different lymphoma subtypes and analyze the correlation between cfDNA concentration and other clinical indices such as serum LDH and IPI. Results: Somatic alterations were identified in cfDNA samples with a median of 64 variants per sample. The concentration of cfDNA in the plasma was found to be significantly correlated with the clinical indices in diffuse large B cell lymphoma (DLBCL). The genetic heterogeneity of different lymphoma subtypes was clearly observed in cfDNAs from germinal center B-cell (GCB) DLBCL, non-GCB DLBCL and natural killer/T-cell lymphoma (NKTCL), confirming that distinct molecular mechanisms are involved in the pathogenesis of different lymphomas. Conclusion: Our findings demonstrate that NGS-based cfDNA mutation profiling reveals genetic heterogeneity across lymphoma subtypes, with potential implications for the discovery of therapeutic targets, the exploration of genome evolution and the development of risk-adapted treatment.

The Clinical Utility of Circulating Epstein-Barr Virus DNA Concentrations in NK/T-Cell Lymphoma: A Meta-Analysis.

BACKGROUND: Circulating Epstein-Barr virus (EBV) DNA concentrations were reported to have prognostic value for NK/T-cell lymphoma patients in limited small-scale studies. In this study, we aimed to evaluate the clinical utility of circulating EBV-DNA concentrations to a large sample of NK/T-cell lymphoma patients. METHODS: We conducted this meta-analysis, which included a total of 15 prospective and retrospective comparable studies to assess the association between pretreatment EBV-DNA (pre-DNA), posttreatment EBV-DNA (post-DNA), and clinical outcomes of NK/T-cell lymphoma patients. We chose overall survival (OS) as the primary endpoint and progression-free survival (PFS), complete response (CR), and overall response rate (ORR) as secondary endpoints. RESULTS: High pre-DNA and detectable post-DNA were both significantly correlated with poorer OS in NK/T-cell lymphoma patients (P < 0.05), with hazard radios (HRs) equal to 3.45 and 2.30, respectively. High pre-DNA and detectable post-DNA also predicted poorer PFS. Additionally, high pre-DNA was found to be significantly correlated with both worse CR and ORR, which indicated worse treatment response. CONCLUSION: Circulating EBV-DNA concentrations provides prognostic values of survival and treatment response in NK/T-cell lymphoma patients.