Diagnostic performance and prognostic value of circulating tumor DNA methylation marker in extranodal natural killer/T cell lymphoma.

Circulating tumor DNA (ctDNA) carries tumor-specific genetic and epigenetic variations. To identify extranodal natural killer/T cell lymphoma (ENKTL)-specific methylation markers and establish a diagnostic and prognosis prediction model for ENKTL, we describe the ENKTL-specific ctDNA methylation patterns by analyzing the methylation profiles of ENKTL plasma samples. We construct a diagnostic prediction model based on ctDNA methylation markers with both high specificity and sensitivity and close relevance to tumor staging and therapeutic response. Subsequently, we built a prognostic prediction model showing excellent performance, and its predictive accuracy is significantly better than the Ann Arbor staging and prognostic index of natural killer lymphoma (PINK) risk system. Notably, we further establish a PINK-C risk grading system to select individualized treatment for patients with different prognostic risks. In conclusion, these results suggest that ctDNA methylation markers are of great value in diagnosis, monitoring, and prognosis, which might have implications for clinical decision-making of patients with ENKTL.

Effect of autologous hematopoietic stem cell transplantation for patients with peripheral T-cell lymphoma in China: A propensity score-matched analysis.

Background: The role of consolidation therapy with autologous stem cell transplantation (ASCT) in patients with peripheral T-cell lymphoma (PTCL) in first complete remission (CR1) or partial remission (PR1) remains controversial. The existing data from China are limited. Therefore, we aimed to investigate the effect of ASCT on the survival of Chinese patients with PTCL showing response to induction chemotherapy at our hospital. Methods: We retrospectively reviewed the data of patients with PTCL (excluding Natural killer/T cell lymphoma) in CR1 or PR1 treated at Peking University Hospital &Institute from 1996 to 2020. Propensity score matching (PSM) was used to balance clinical characteristics between the ASCT and non-ASCT groups. The primary endpoints were event-free survival (EFS) and overall survival (OS). Results: Of the 414 selected patients, 73 received ASCT consolidation and 341 did not. Over a median follow-up of 5.7 years, survival was significantly better in the ASCT group than in the non-ASCT group (median EFS, 8.1 years vs. 2.8 years, P = 0.002; median OS, 14.9 years vs. 10.2 years, P = 0.007). The 5-year EFS and OS rates were 68.4% and 77.0% in ASCT group, and 43.2% and 57.6% in non-ASCT group, respectively. The survival benefit was confirmed in the propensity score matched cohort (46 patients who received ASCT and 84 patients who did not receive ASCT): P = 0.007 for median EFS and P = 0.022 for the median OS. Cox regression analysis showed that ASCT was independently associated with better survival: hazard ratio (HR) for EFS, 0.46 (95% CI: 0.28-0.76); HR for OS, 0.50 (95% CI: 0.31-0.84). Subgroup analysis showed that ASCT was more likely to benefit higher-risk patients and those with advanced disease. Among the subtypes of PTCL, the benefit was significant in angioimmunoblastic T-cell lymphoma (HR = 0.26 [95% CI: 0.10-0.66] for EFS and 0.29 [95% CI: 0.12-0.74] for OS), but not in the other subtypes. Conclusion: ASCT may improve the long-term survival of patients with PTCL in first CR or PR, especially for patients with angioimmunoblastic T-cell lymphoma. The specific groups most likely to benefit from upfront ASCT need to be clearly identified.

A Prospective Phase II Study of Pegaspargase-COEP Plus Radiotherapy in Patients With Newly Diagnosed Extra-Nodal NK/T-Cell Lymphoma.

Background: The optimal first-line treatment for extra-nodal NK/T-cell lymphoma (ENKTL) has not been well-defined. This study aimed to evaluate the efficacy and safety of pegaspargase, cyclophosphamide, vincristine, etoposide and prednisone (COEPL) regimen combined with radiotherapy for patients with newly diagnosed ENKTL. Methods: Our study is a prospective, open-label clinical trial. Patients with newly diagnosed ENKTL and an ECOG performance status of 0 to 2 were eligible for enrollment. For patients with stage I/II nasal ENKTL, treatment included 2 cycles of induction COEPL regimen followed by concurrent chemoradiotherapy, then by 2 cycles of COEPL regimen as consolidation. For patients with stage III/IV or primary extra-nasal ENKTL, treatment included 6-8 cycles of COEPL regimen with or without radiotherapy to local sites, and autologous stem cell transplantation was given in selected patients. Results: A total of 80 patients were enrolled. The median age was 41 years (range, 15-76 years). Sixteen patients (20%) had stage III/IV disease, and 10 (12.5%) had a PINK score≥2. Complete response and overall response rates were 75.9% and 87.3%, respectively. With a median follow-up of 41.4 months (range 2.7-76.2 months), the 3-year progression-free survival (PFS) and overall survival (OS) rates were 71.3% (95%CI 61.1-81.5%) and 73.3% (95%CI 63.1-83.5%), respectively. For patients with stage I/II nasal ENKTL (n=62), the 3-year PFS and OS were 78.1% and 81.2%, respectively. For patients with stage III/IV or primary extra-nasal ENKTL (n=18), 3-year PFS and OS were 48.1% and 45.7%, respectively. Major grade 3-4 adverse events were anemia (21.3%), leucopenia (22.5%), neutropenia (18.8%), and thrombocytopenia (7.6%). No treatment-related death was observed. Conclusions: Pegaspargase-COEP chemotherapy in combination with radiotherapy is highly effective and safe for patients with newly diagnosed ENKTL.

Clinical Significance of Plasma Epstein-Barr Virus DNA in Peripheral T-Cell Lymphomas.

INTRODUCTION: The clinical implications of plasma Epstein-Barr virus (EBV) DNA in patients with peripheral T-cell lymphoma (PTCL) remain unclear. OBJECTIVE: This study aimed to explore the clinical correlations of pre- and post-treatment plasma EBV-DNA concentrations with treatment outcomes and prognosis in patients with PTCL. METHODS: We retrospectively reviewed 128 patients diagnosed with PTCL with available data on pre-treatment plasma EBV-DNA, including 63 patients for whom post-treatment plasma EBV-DNA data were also available. Patients with extra-nodal NK/T-cell lymphoma were excluded from this study. RESULTS: Pre-treatment plasma EBV-DNA was elevated (e.g., ≥500 copies/mL) in 35.2% of PTCL patients, with significant differences in positive rates between different subtypes of PTCL (p < 0.001). High pre-treatment EBV-DNA concentrations were associated with advanced age (>60 years), elevated lactate dehydrogenase levels, high International Prognostic Index (IPI), and positive EBV-encoded RNAs-ISH in tumor specimens. In multivariate analyses, pre-treatment EBV-DNA ≥500 copies/mL was an independent prognostic factor after adjusting for IPI and pathological subtypes (hazard ratio = 2.14, p = 0.032). For patients with elevated pre-treatment EBV-DNA, normalization of EBV-DNA concentrations after first-line chemotherapy was significantly associated with better overall response rate (81.3% vs. 22.2%, p = 0.014), progression-free survival (12.0 months vs. 3.7 months, p = 0.011), and overall survival (37.9 months vs. 7.8 months, p = 0.012). For patients achieving remission to first-line therapy, rebound of EBV-DNA levels during follow-up was associated with disease relapse or progression. CONCLUSIONS: These results suggest that pre-treatment plasma EBV-DNA concentration is a strong prognostic factor for PTCL. For patients with elevated pre-treatment EBV-DNA, dynamic monitoring of EBV-DNA changes after initiation of therapy is useful for predicting treatment outcome and disease relapse.

A Novel Mechanism of Action of Histone Deacetylase Inhibitor Chidamide: Enhancing the Chemotaxis Function of Circulating PD-1(+) Cells From Patients With PTCL.

BACKGROUND: Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of neoplasms characterized by a poor prognosis. Histone deacetylase (HDAC) inhibitors have emerged as novel therapeutic agents for PTCLs. In this study, we aimed to explore the immunomodulatory effect of the HDAC inhibitor chidamide on circulating PD-1(+) cells from patients with PTCL, as well as its correlation with treatment response. METHODS: We enrolled newly diagnosed patients with PTCLs treated with a combination of chidamide and chemotherapy. Gene expression profile analysis was performed on peripheral blood PD-1(+) cells, both at baseline and at the end of treatment. A list of differentially expressed genes (DEGs) was identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to annotate the biological implications of the DEGs. A gene concept network was constructed to identify the key DEGs for further PCR verification. RESULTS: A total of 302 DEGs were identified in the complete remission (CR) group, including 162 upregulated and 140 downregulated genes. In contrast, only 12 DEGs were identified in the non-CR group. GO analysis revealed that these upregulated DEGs were mainly involved in chemokine activity, cell chemotaxis, and cellular response to interleukin-1 and interferon-γ. Furthermore, KEGG pathway analysis showed that these DEGs were enriched in cytokine-cytokine receptor interaction and chemokine signaling pathways. The innate immune signaling pathways, including the Toll-like and NOD-like receptor signaling pathways, were also influenced. The gene concept network revealed that the key upregulated genes belonged to the C-C chemokine family. CONCLUSION: Our results showed that chidamide treatment notably enhanced the expression of genes associated with chemokine activity and chemotaxis function of circulating PD-1(+) cells. By recruiting immune cells and improving the innate immune function of PD-1(+) cells, chidamide may reshape the tumor microenvironment to an anti-tumor phenotype and synergize with checkpoint inhibitors.

Prognostic Nomogram for Childhood Acute Lymphoblastic Leukemia: A Comprehensive Analysis of 673 Patients.

OBJECTIVE: Despite that the survival rate in childhood acute lymphoblastic leukemia (cALL) is excellent, subsets of high-risk patients with cALL still have high relapse rates, and the cure rate is well below that for which we should aim. The present study aims to construct a prognostic nomogram to better inform clinical practitioners and improve risk stratification for clinical trials. METHODS: The developed nomogram was based on the therapeutically applicable research to generate effective treatment (TARGET) database. With this database, we obtained 673 cALL patients with complete clinical information. We identified and integrated significant prognostic factors to build the nomogram model by univariate and multivariate Cox analysis. The predictive accuracy and discriminative ability of the nomogram were determined by the concordance index (C-index), calibration curve, and area under the receiver operating characteristic (ROC) curve (AUC) of ROC analysis. Internal validations were assessed by the bootstrapping validation. RESULTS: In the multivariate analysis of the primary cohort, the independent factors for survival were ETV6 RUNX1 fusion status, karyotype, minimal residual disease (MRD) at day 29, and DNA index, which were all integrated into the nomogram. The calibration curve for the probability of survival showed good agreement between the prediction by the nomogram and the actual observation. The C-index of the nomogram for predicting survival was 0.754 (95% CI, 0.715-0.793), and the AUCs for 3-, 5-, and 7-year survival were 0.775, 0.776, and 0.772, respectively. CONCLUSION: We comprehensively evaluated the risk of clinical factors associated with prognosis and carried out risk stratification. The nomogram proposed in this study objectively and accurately predicted the prognosis of children with ALL.

Successful treatment with lenalidomide plus chidamide combination therapy in 3 heavily treated patients with non-Hodgkin lymphoma: Three cases report.

RATIONALE: The prognosis of patients with aggressive relapsed or refractory (R/R) non-Hodgkin lymphoma (NHL) remains poor. Both immunomodulatory drugs and histone deacetylase inhibitors have demonstrated activity against R/R NHL; yet, the combination of these 2 targeted therapies has rarely been explored. PATIENT CONCERNS: Here, we report 3 cases. Case 1 was a 68-year-old woman who presented to our hospital with dyspnea. Case 2 was a 75-year-old man with massive upper gastrointestinal bleeding. Case 3 was a 62-year-old woman with cough, dyspnea, and lymphadenopathy. DIAGNOSIS: The biopsy results revealed diffuse large B cell lymphoma (DLBCL), DLBCL, and angioimmunoblastic T-cell lymphoma, for Case 1, 2, and 3 respectively. INTERVENTION: All 3 patients experienced relapse after first-line therapy and multiple lines of salvage therapy. Finally, they all received lenalidomide combined with chidamide. OUTCOMES: All 3 patients achieved complete and durable remission. Case 1 relapsed again after 3 months, while the other 2 cases remained in complete remission. LESSONS: To our knowledge, this is the first report of lenalidomide combined with chidamide for the treatment of R/R NHL. Our findings warrant further evaluation of this novel chemo-free therapy in future prospective clinical trials.

Prognostic value of interim 18F-FDG PET/CT in T-cell lymphomas.

18F-FDG PET/CT is recommended for staging and response assessment in FDG-avid lymphomas, such as HL and DLBCL. But evidence of PET/CT regarding T-cell lymphomas (TCLs) was limited. In this retrospective study, we conducted survival analysis using interim PET/CT in 51 TCLs patients. PET/CT were reported using the Deauville 5-point score (DS) and the ΔSUVmax. In univariate analysis, I-PET/CT had a significant prognostic value of survival outcomes based on DS (p < .001 for progression-free survival (PFS), p = .010 for overall survival (OS)) and ΔSUVmax (p < .001 for PFS, p = .023 for OS). In multivariate analysis, DS remained a statistically independent predictor of PFS (p < .001) and OS (p = .017). ΔSUVmax remained a statistically independent predictor of PFS (p = .008), but not of OS (p = 0.311). Therefore, DS on I-PET/CT had a remarkable value of predicting survival outcomes in TCLs.

Circulating PD-1 (+) cells may participate in immune evasion in peripheral T-cell lymphoma and chidamide enhance antitumor activity of PD-1 (+) cells.

Peripheral T-cell lymphoma (PTCL) is a heterogeneous disease with poor outcomes. We intend to explore the role of circulating PD-1 (+) cells in tumor immune evasion in PTCL patients and the mechanism of chidamide as a regulator of immune-associated medicine on PD-1 (+) cells. Gene expression profiling (GEP) was performed on circulating PD-1 (+) cells from 22 PTCL patients and 13 healthy subjects, and circulating PD-1 (-) cells from 2 PTCL patients. PD-1 (+) cells were treated with chidamide, and the production IFN-γ and cytotoxicity were analyzed. GEP were performed on circulating PD-1 (+) cells from 2 PTCL patients treated with chidamide combined with chemotherapy and 1 patient treated with traditional chemotherapy. GEP showed that genes associated with innate immune response were abnormally expressed in PD-1 (+) cells of PTCL patients compared with healthy subjects, meanwhile the expression of CTLA-4 was significantly higher in PD-1 (+) cells than that of PD-1 (-) cells. In vitro study revealed decreased level of IFN-γ secretion and impaired cytotoxic activity of PD-1 (+) cells compared with PD-1 (-) cells, while chidamide could recover the deficiencies and upregulate adaptive immune-associated genes in PD-1 (+) cells of PTCL patients. Our research indicated that PD-1 (+) cells might have deficiencies in innate and adaptive immune response and chidamide may reverse the defects.

Autoimmune disease-associated non-Hodgkin's lymphoma-a large retrospective study from China.

The incidence and clinical implications of autoimmune diseases (ADs) in patients with non-Hodgkin's lymphoma(NHL) remain unclear. The aim of this study was to examine the prevalence of ADs in NHL and define the clinical characteristics and prognosis of AD-associated NHL patients. Patients diagnosed with NHL in our institute between 1995 and 2017 were retrospectively reviewed to assess the incidence of ADs. Of 4880 patients with NHL, 140 (2.9%) presented with autoimmunity, with a total of 24 ADs. The most common AD was Sjögren syndrome, followed by autoimmune cytopenia, psoriasis, rheumatoid arthritis, etc. Psoriasis and rheumatoid arthritis were significantly associated with pre-existing ADs, whereas autoimmune cytopenia was significantly associated with secondary AD. Sjögren syndrome was significantly associated with B-cell lymphoma, and systemic vasculitis was significantly associated with T-cell lymphoma. Patients with AD-associated NHL had a high frequency of extranodal involvement(87%), with significant associations between specific extranodal sites of lymphoma and subtypes of ADs. Among patients with available data on pre-treatment peripheral blood Epstein-Barr virus (EBV) DNA(n = 68), elevated EBV-DNA load was observed in a variety of NHL subtypes, including 20% of marginal zone lymphoma and 14.3% of follicular lymphoma patients. In a matched-pair analysis, survival did not differ significantly between NHL patients with and without ADs. However, for NHL patients with pre-existing ADs, a prior history of systemic corticosteroids therapy was significantly associated with worse survival (HR = 7.33, P = 0.006). Taken together, our data suggest that a broad spectrum of ADs is associated with NHL, and AD-associated NHL has distinct features with regard to clinical manifestations and prognosis.

Primary breast diffuse large B-cell lymphoma in the rituximab era: Therapeutic strategies and patterns of failure.

Primary breast diffuse large B-cell lymphoma (PB-DLBCL) is a rare subtype of DLBCL with limited data on patterns of failure. This multicenter study aimed to define the optimum treatment strategy and patterns of failure for PB-DLBCL patients. We retrospectively reviewed data on 108 PB-DLBCL patients from 21 Chinese medical centers. Only patients with localized disease (involvement of breast and localized lymph nodes) were included. After a median follow-up of 3.2 years, 32% of patients developed progression or relapse. A continuous pattern of relapse was observed, characterized by frequent late relapses in the contralateral breast and central nervous system (CNS). Although rituximab significantly reduced the overall cumulative risk of progression or relapse (5-year cumulative risk 57% vs 24%, P = .029), it had limited effect on the reduction of breast relapse (P = .46). Consolidative radiotherapy significantly decreased the risk of breast relapse, even in the subgroup of patients treated with rituximab (5-year cumulative risk 21.2% vs 0%, P = .012). A continuous risk of CNS progression or relapse up to 8.2 years from diagnosis was observed (10-year cumulative risk 28.3%), with a median time to CNS relapse of 3.1 years. Neither rituximab nor prophylactic intrathecal chemotherapy significantly decreased the risk of CNS relapse. In summary, our study indicates that PB-DLBCL has a continuous pattern of relapse, especially with frequent late relapses in the CNS and contralateral breast. Rituximab and RT confer complementary benefit in the reduction of relapse. However, neither the addition of rituximab nor prophylactic intrathecal chemotherapy could effectively prevent CNS relapse for PB-DLBCL patients.

The optimal timing of radiotherapy in the combined modality therapy for limited-stage extranodal NK/T cell lymphoma (ENKTL): a systematic review and meta-analysis.

The optimal timing and sequencing of radiotherapy (RT) and chemotherapy (CT) in the treatment of limited-stage extranodal NK/T cell lymphoma (LS-ENKTL) has not been elucidated. The aim of this meta-analysis was to evaluate whether the timing of RT in relation to CT affects the survival of patients with LS-ENKTL. We searched Medline, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, Clinicaltrials.gov , and relevant meeting abstract databases from inception through April 2018 without age or language restrictions. Studies comparing upfront RT plus CT with induction CT followed by RT in patients with LS-ENTKL were eligible for inclusion. Seven studies with 1593 patients were included, and all were retrospective cohort studies. Compared with induction CT followed by RT, upfront RT significantly improved OS of patients with LS-ENTKL (HR = 0.70, 95%CI 0.55-0.88, P = 0.002), with no evidence of heterogeneity across studies (I2 = 0%). In subgroup analyses, the beneficial effect of upfront RT on survival did not differ significantly between subgroups of studies with different types of chemotherapy regimens (anthracycline-based or non-anthracycline-based), the administration of concurrent chemoradiotherapy or not, and different median doses of RT (≥ 45 or < 45 Gy). These results suggest that upfront RT plus CT confers survival advantage over induction CT followed by RT for the treatment of LS-ENTKL, and this survival advantage is not significantly affected by the types of CT regimens or timing of CT. Given the retrospective nature of included studies, these results should be interpreted with caution in clinical practice.

Comparison of gemcitabin, cisplatin, and dexamethasone (GDP), CHOP, and CHOPE in the first-line treatment of peripheral T-cell lymphomas.

OBJECTIVES: Optimal chemotherapy regimen for peripheral T-cell lymphomas (PTCL) has not been fully defined. This study aimed to evaluate the optimal chemotherapy regimen in the first-line treatment for PTCL patients. METHODS: Between 2003 and 2014, 93 consecutive patients with PTCL were enrolled in this study. Of 93 patients, 42 patients received CHOPE, 40 patients with CHOP, and 11 patients with GDP regimen. RESULTS: Response could be evaluated in 88 of 93 patients at the end of primary treatment. The CR rate for patients received CHOP (n = 38), CHOPE (n = 39), and GDP (n = 11) were 28.9, 51.3, and 45.5%, respectively, (P = 0.132) with an ORR of 65.8, 76.9, and 90.9%, respectively, (P = 0.210). The median follow-up time was 17.1 (1.4-108.3) months. Median progression-free survival (PFS) in CHOP (n = 40), CHOPE (n = 42), and GDP (n = 11) groups were 6.0, 15.3, and 9.7 months (P = 0.094) with 1-year PFS of 35.0, 54.8, and 45.5%, respectively, (P = 0.078). One-year OS for patients received CHOP (n = 40), CHOPE (n = 42), and GDP (n = 11) were 65.0, 83.3, and 100%, respectively, (P = 0.013) (CHOP vs CHOPE, P = 0.030; CHOP vs GDP, P = 0.024; CHOPE vs GDP, P = 0.174). CONCLUSION: CHOPE has a trend to improve CR rate, 1-year PFS and OS compared with CHOP alone. GDP shows promising efficacy which worth further exploration in large cohort studies. Clinical experience presented in this study may serve as reference for future large cohort studies.

Predictive value of EGFR overexpression and gene amplification on icotinib efficacy in patients with advanced esophageal squamous cell carcinoma.

This study aimed to search for a molecular marker for targeted epithelial growth factor receptor (EGFR) inhibitor Icotinib by analyzing protein expression and amplification of EGFR proto-oncogene in esophageal squamous cell carcinoma (ESCC) patients.Immunohistochemistry and fluorescence in situ hybridization (FISH) was used to assess EGFR expression and gene amplification status in 193 patients with ESCC. We also examined the association between EGFR overexpression and the efficacy of a novel EGFR TKI, icotinib, in 62 ESCC patients.Of the 193 patients, 95 (49.2%) patients showed EGFR overexpression (3+), and 47(24.4%) patients harbored EGFR FISH positivity. EGFR overexpression was significantly correlated with clinical stage and lymph node metastasis (p<0.05). In addition, EGFR overexpression was significantly correlated with EGFR FISH positivity (p<0.001). Among the 62 patients who received icotinib, the response rate was 17.6% for patients with high EGFR-expressing tumors, which was markedly higher than the rate (0%) for patients with low to moderate EGFR-expressing tumors (p=0.341). Furthermore, all cases responded to icotinib showed EGFR overexpression.In conclusion, our study suggests that EGFR overexpression might potentially be used in predicting the efficacy in patients treated with Icotinib. These data have implications for both clinical trial design and therapeutic strategies.

[Efficacy and safety evaluation of gemcitabine combined with ifosfamide in patients with advanced nasopharyngeal carcinoma after failure of platinum-based chemotherapy].

OBJECTIVE: To evaluate the efficacy and safety of gemcitabine combined with ifosfamide (GI regimen)in patients with recurrent or metastatic nasopharyngeal carcinoma after failure of platinum-based chemotherapy. METHODS: The clinical data of 27 nasopharyngeal carcinoma patients, who received GI regimen between April 2005 and March 2014 after failure of prior platinum-based chemotherapy, were retrospectively reviewed,and relevant prognostic factors were explored. RESULTS: All patients were evaluable for efficacy and toxicity. No patient achieved complete response (CR). Partial response (PR) was achieved in ten patients, stable disease (SD) in thirteen patients, progressive disease (PD) in four patients, with a response rate of 37.0% and an overall disease control rate (PR+SD) of 85.2%. For ten PR patients, the median duration of response was 5.5 months. The median progression-free survival of the whole group was 6.7 months, and the Kaplan-Meier estimate of median overall survival was 17.4 months. The 1-year survival rate was 72.6%. Toxicity was mainly hematological: Grade III or IV anemia, neutropenia and thrombocytopenia were found in 3.7%, 37.0% and 18.5% of all patients, respectively. Univariate and multivariate analyses indicated that dose intensity of gemcitabine was a significant prognostic factor for PFS, whereas salvage treatment after failure of GI regimen was a significant prognostic factor for OS. CONCLUSIONS: Gemcitabine and ifosfamide combination is effective and well tolerated by patients with advanced nasopharyngeal carcinoma pretreated with platinum-based chemotherapy. Further clinical study is warranted.

Addition of rituximab is not associated with survival benefit compared with CHOP alone for patients with stage I diffuse large B-cell lymphoma.

BACKGROUND: The role of rituximab in combination with CHOP regimen in patients with stage I diffuse large B-cell lymphoma (DLBCL) remains to be defined. We aimed to compare CHOP plus rituximab (R-CHOP) with CHOP alone and determine the value of radiotherapy in these patients. METHODS: Between 2003 and 2009, 140 untreated patients with stage I DLBCL were retrospectively analyzed in this study. RESULTS: Seventy-eight patients were treated in R-CHOP group and 62 in CHOP group. Ninety-one patients received additional radiotherapy at the end of chemotherapy. The different treatment groups were well-balanced with respect to baseline characteristics. Complete response (CR) rate was 77% both in R-CHOP and CHOP groups (P=0.945). After a median follow-up period of 56 months, patients received R-CHOP regimen had similar 5-year progression-free survival (PFS) (76% vs. 85%; log-rank P=0.215) and 5-year overall survival (OS) (90% vs. 96%; log-rank P=0.175) compared with those with CHOP alone. Patients with radiotherapy had significantly increased 5-year PFS compared with those who had chemotherapy alone (86% vs. 71%; log-rank P=0.005). At multivariate analysis, patients who had CR (P=0.008) and received radiotherapy (P=0.003) were significantly associated with superior PFS. CONCLUSIONS: CHOP alone could be as effective as R-CHOP regimen and additional radiotherapy would be necessary for stage I or stage I non-bulky DLBCL patients.

Systemic chemotherapy followed by locoregional definitive intensity-modulated radiation therapy yields prolonged survival in nasopharyngeal carcinoma patients with distant metastasis at initial diagnosis.

Chemotherapy is the current mainstay of treatment for patients with newly diagnosed metastatic nasopharyngeal carcinoma (NPC), whereas the role of locoregional radiotherapy remains to be defined. In this study, we retrospectively evaluated the outcome of systemic chemotherapy followed by locoregional definitive intensity-modulated radiation therapy (IMRT) as first-line treatment for these patients. Forty-one patients with pathologically confirmed NPC with distant metastasis at initial diagnosis seen between March 2005 and February 2014 were included. All the patients were treated with platinum-based systemic chemotherapy followed by definitive IMRT to the primary head and neck region with or without concurrent chemotherapy. In addition, local treatment to metastatic lesions was given in 19 patients. With a median follow-up time of 25 months, 24 patients had died, and the estimated median overall survival time was 31.2 months. The 1-, 2-, 3- and 5-year estimated OS rates were 89.9, 67.4, 41.1 and 22.5%, respectively. Prognostic analyses showed that serum lactate dehydrogenase level (P = 0.021) and number of metastatic sites (single vs. multiple; P = 0.016) were significant prognostic factors. Five patients are still alive without evidence of disease after 52 to >101 months. All of them had a single metastatic lesion and received local treatment to metastatic sites. These results suggest that the use of definitive IMRT to treat the locoregional tumor in combination with systemic chemotherapy may prolong survival in patients with newly diagnosed metastatic NPC, making curability a possible consideration in selected patients with single metastasis. Further prospective clinical trials are warranted.

[Analysis of 54 mental disability reappraisal cases due to brain damage].

OBJECTIVE: To investigate the different kinds of controversial cases of mental disability after brain damage, to analysis the problems in the first appraisal, and to explore solutions of the problems. METHODS: The reappraisals of mental disorders after traumatic brain damage were collected from 2007-2011 in Shanghai forensic center, and the first appraisal and reappraisal cases were analyzed and compared. RESULTS: The changes of conclusion in reappraisal cases showed the following major reasons: inappropriate appraisal time, not comprehensive and object investigation of mental state of patients in first appraisal, misunderstanding the standards, etc. CONCLUSION: The quality improvement of appraisal should adopt the following measures: regulating the practice, improvement of the professional skills of experts, choosing appropriate appraisal time, improvement of appraisal standards, etc.