Differential Impact of Relative Dose-Intensity Reductions in Diffuse Large B-Cell Lymphoma Treated with R-CHOP21 or R-CHOP14

DLBCL is an aggressive lymphoma treated with R-CHOP. Recently, attempts have been made to improve the outcome by increasing both dose-density and intensity but there have been no benefits in terms of survival. When treating malignancies RDI is important to consider but there is little published information on DLBCL. The purpose of this study was to analyze the differential prognostic impact of RDI in two cohorts of DLBCL patients treated with R-CHOP21 or R-CHOP14. From January 2001 to August 2013 we included DLBCL patients homogenously treated with R-CHOP21 or R-CHOP14, with or without radiotherapy, at University Hospital Son Espases, Hospital Son Llatzer of Palma and Hospital del Mar of Barcelona (N = 157). In order to avoid selection bias the patients were retrospectively identified from the Pathology Department and Pharmacy registries. Median follow-up was 68 months. There was no difference in the response or survival between the two cohorts. In the R-CHOP21 group, both a reduction higher than 15% in RDI (RR 7.41) and R-IPI (RR 2.99) were independently associated with OS. However, a reduction higher than 15% in RDI (RR 4.41) was only noted for PFS. In the R-CHOP14 group, NCCN-IPI (RR 7.09) and B-symptoms (RR 5.37) for OS; AA stage III-IV (RR 6.26) and bulky disease (RR 4.05) for PFS. There was a trend towards a higher rate of RDI reduction observed in the R-CHOP14 group but it only made an impact in the R-CHOP21 group. We conclude that R-CHOP21 and R-CHOP14 are equivalent regimens in terms of response and survival, but only if RDI reductions are avoided. For patients receiving R-CHOP21 we recommend using clinical and support measures in order to avoid RDI reductions.     

Clinical Analysis of the HBV Infection Status of 135 Patients with Diffuse Large B Cell Lymphoma Treated with R-CHOP or CHOP/CHOP-Like Chemotherapy

Objectives

This study aimed to determine the HBV infection status of 135 patients with DLBCL (diffuse large B cell lymphoma), to analyze the overall survival (OS) and progression-free survival (PFS) of the different HBV infection status groups, and to discuss the relationship between HBV serological test results and the prognosis of DLBCL patients.

Methods

A retrospective analysis was performed of the clinical data, HBV serological test results, and PFS/OS of 135 DLBCL patients who were initially diagnosed and treated with more than 3 cycles of an R-CHOP/CHOP/CHOP-like regimen at our center from January 1, 2008 to December 31, 2012.

Results

The patients in the HBV infection group were older at disease onset (≥60 years old) and were more likely to present with stage 3-4 disease compared with the HBV-free group (P = 0.030 and P = 0.025, respectively). Approximately 50% of the patients with an active HBV infection required a reduction in the chemotherapy dose, and 66.7% of the patients in this group received more than 1 line of therapy; these rates were significantly higher than those in the no infection group (P = 0.003 and P = 0.011, respectively). Although HBV infection had no obvious influence on the outcome of first-line therapy, patients with an inactive infection had a higher relapse/progression rate within 3 months after a CR/PR than patients with an active infection (14/20 vs. 1/12, P = 0.001). The PFS at 1 year, 3 years and OS rates at 1 year, 3 years were significantly lower in the active HBV infection group than in the HBV-free group (P = 0.008, P = 0.002, P = 0.004, and P = 0.002, respectively). The PFS rates at 1 year and 3 year in HBV-free group were higher than those in the HBV infection group (80.5% and 52.9% P = 0.001, 78.1% and 44.4% P = 0.002). The lymphoma-related mortality rates were 2.7% in the no infection group, 19.2% in the HBV infection group (P = 0.004), and 28.6% in the active HBV infection group (P = 0.001). Among the patients treated with MabThera, the PFS in the HBV infection group was 11 months in the HBV infection group and 67 months in the infection-free group (P = 0.000). A Cox regression model of PFS revealed that age ≥60 years and HBV infection were independent prognostic factors (age: P = 0.019, HR = 2.002, 95% CI 1.123-3.567; HBV infection: P = 0.026, HR = 0.494, 95% CI 0.265-0.919).

Conclusion

Compared with the patients in HBV-free group, those in the HBV infection group were older at disease onset, and the active infection patients presented with more advanced disease and had a lower PFS at 1, 3 years as well as a lower OS at 3 years. The patients in the inactive infection group had a higher progression/relapse rate within 3 months after a CR/PR than those in the active infection group. HBV infection was an unfavorable factor for PFS in the MabThera group. An age ≥60 years and HBV infection were independent unfavorable prognostic factors for PFS.     

Homozygous A polymorphism of the complement C1qA 276 correlates with prolonged overall survival in patients with diffuse large B cell lymphoma treated with R-CHOP

ABSTRACT: BACKGROUND: The precise mechanism of action for rituximab (R) is not fully elucidated. Besides antibodydependent cellular cytotoxicity (ADCC), complements may also play an important role in the clinical response to rituximab-based therapy in diffuse large B cell lymphoma (DLBCL). The purpose of this study was to explore the relationship between C1qA[276] polymorphism and the clinical response to standard frontline treatment with R-CHOP in DLBCL patients. METHODS: Genotyping for C1qA[276A/G] was done in 164 patients with DLBCL. 129 patients treated with R-CHOP as frontline therapy (R [greater than or equal to] 4 cycles) were assessable for the efficacy. RESULTS: Patients with homozygous A were found to have a higher overall response rate than those with heterozygous or homozygous G alleles (97.3% vs. 83.7%,P = 0.068). The complete response rate in patients with homozygous A was statistically higher than that in AG and GG allele carriers (89.2% vs. 51.1%,P = 0.0001). The overall survival of patients with homozygous A was longer than that of the G allele carriers (676 days vs. 497 days, P = 0.023). Multivariate Cox regression analysis showed that C1qA A/A allele was an independent favorable prognostic factor for DLBCL patients treated with R-CHOP as firstline therapy. CONCLUSION: These results suggest that C1qA polymorphism may be a biomarker to predict response to RCHOP as frontline therapy for DLBCL patients.     

The Expression of CD30 Based on Immunohistochemistry Predicts Inferior Outcome in Patients with Diffuse Large B-Cell Lymphoma

The prognostic value of CD30 expression indiffuse large B-cell lymphoma (DLBCL)remains controversial. Herein, we performed this retrospective study to investigate the clinical and prognostic significance of CD30 expression in patients with DLBCL.Among all the 146 patients, the expression of CD30 was observed in 23 cases (15.7%).The DLBCL patients with CD30 expression showed more likely to present B symptoms, bone marrow involvement, non-germinal centre B-cell-like (Non-GCB) DLBCL, BCL-2 and Ki-67overexpression(p<0.05). Patients with CD30 expression showed significantly poor overall and event-free survivalcompared with CD30 negative patients(p = 0.031 and 0.041, respectively), especially those with the high intermediate/high-risk international prognostic index (IPI)(p = 0.001 and 0.007, respectively). The prognostic value of CD30expression retained in DLBCL patients treated with eitherCHOP (cyclophosphamide, doxorubicin, vincristine,prednisone) or R-CHOP(rituximab+CHOP). The multivariate analysisrevealed that the expression of CD30 remained an unfavorable factor for both overall and event-free survival (p = 0.001 and 0.002, respectively).In conclusion, these data suggest that CD30 is expressed predominantly in Non-GCBDLBCL. The expression of CD30 implied poor outcomein DLBCL patientstreated with either CHOP or R-CHOP, especially those with the high intermediate/high-risk IPI, possibly indicating that anti-CD30 monoclonal antibody could be of clinical interest.     

A New Prognostic Score for Elderly Patients with Diffuse Large B-Cell Lymphoma Treated with R-CHOP: The Prognostic Role of Blood Monocyte and Lymphocyte Counts Is Absent

Background

Absolute lymphocyte count (ALC) and absolute monocyte count (AMC) have been documented as independent predictors of survival in patients with newly diagnosed Diffuse Large B-cell Lymphoma (DLBCL). Analysis of the prognostic impact of ALC and AMC in the context of International Prognostic Index (IPI) and other significant variables in elderly population treated in the R-CHOP regime has not been carried out yet.

Methodology/Principal Findings

In this retrospective study, a cohort of 443 newly diagnosed DLBCL patients with age ≥60 was analyzed. All patients were treated with the R-CHOP therapy. An extensive statistical analysis was performed to identify risk factors of 3-year overall survival (OS). In multivariate analysis, only three predictors proved significant: Eastern Cooperative Oncology Group performance status (ECOG), age and bulky disease presence. These predictors were dichotomized (ECOG ≥1, age ≥70, bulk ≥7.5) to create a novel four-level score. This score predicted 3-year OS of 94.0%, 77.4%, 62.7% and 35.4% in the low-, low-intermediate, high-intermediate and high-risk groups, respectively (P<0.001). Further, a three-level score was tested which stratifies the population better (3-year OS: 91.9%, 67.2%, 36.2% in the low, intermediate and high-risk groups, respectively) but is more difficult to interpret. Both the 3- and 4-level scores were compared to standard scoring systems and, in our population, were shown to be superior in terms of patients risk stratification with respect to 3-year OS prediction. The results were successfully validated on an independent cohort of 162 patients of similar group characteristics.

Conclusions

The prognostic role of baseline ALC, AMC or their ratio (LMR) was not confirmed in the multivariate context in elderly population with DLBCL treated with R-CHOP. The newly proposed age-specific index stratifies the elderly population into risk groups more precisely than the conventional IPI and its existing variants.     

MYC Expression in Concert with BCL2 and BCL6 Expression Predicts Outcome in Chinese Patients with Diffuse Large B-Cell Lymphoma,Not Otherwise Specified

Recent studies provide convincing evidence that a combined immunohistochemical or fluorescence in situ hybridization (FISH) score of MYC, BCL2, BCL6 proteins and MYC translocations predicted outcome in diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). However, by far, all these researches are based on Western populations. Therefore, we investigate the prognostic relevance of MYC-, BCL2- and BCL6-rearrangements and protein expression by immunohistochemistry and FISH from 336 de novo DLBCL, NOS treated with CHOP or R-CHOP. Breaks in MYC and BCL6, and fusion in IGH/BCL2 were detected in 9.7%, 20.0%, and 11.1% of the cases, respectively, and were not significantly associated with clinical outcomes. Protein overexpression of MYC (≥40%), BCL2 (≥70%) and BCL6 (≥50%) was encountered in 51%, 51% and 36% of the tumors, respectively. On the basis of MYC, BCL2 and BCL6 expression, double-hit scores (DHSs) and triple-hit score (THS) were assigned to all patients with DLBCL. Patients with high MYC/BCL2 DHS, high MYC/BCL6 DHS and high THS had multiple adverse prognostic factors including high LDH level, poor performance status, advanced clinical stage, high International Prognostic Index (IPI) score, and non-germinal center B-cell. In univariate analysis, high MYC/BCL2 DHS, high MYC/BCL6 DHS and high THS were associated with inferior OS and PFS in both CHOP and R-CHOP cohorts (P<0.05). The highly significant correlations with OS and PFS were maintained in multivariate models that controlled for IPI (P<0.05). DLBCLs with high DHSs and high THS share the clinical features and poor prognosis of double-hit lymphoma (P>0.05). These data together suggest that the immunohistochemical DHSs and THS defined a large subset of DLBCLs with double-hit biology and was strongly associated with poor outcome in patients treated with R-CHOP or CHOP.     

Expression of DBC1 and Androgen Receptor Predict Poor Prognosis in Diffuse Large B Cell Lymphoma

BACKGROUND: Recently, deleted in breast cancer 1 (DBC1) has been suggested as a poor prognostic indicator of various human cancers and may possibly have a role as a coactivator of androgen receptor (AR). However, their roles in lymphoma are still unknown. MATERIALS AND METHODS: We investigated the effect of the expression of DBC1 and AR in diffuse large B cell lymphoma (DLBCL). Immunohistochemical expression of DBC1 and AR were evaluated in 101 DLBCL samples by tissue microarray. RESULTS: Positive expression of DBC1 and AR was seen in 73% and 70% of DLBCL, respectively. In total DLBCL patients, DBC1 and AR expression were significantly associated with high clinical stage, elevated serum lactate dehydrogenase levels, and high international prognostic index scores, and they predicted shorter overall survival (OS) and relapse-free survival (RFS) by univariate analysis. DBC1 expression was also an independent prognostic indicator by multivariate analysis (OS, P = .017; RFS, P = .004). Especially, both DBC1 and AR expression significantly correlated with shorter OS and RFS in non-germinal center B cell (non-GCB)-type DLBCL by univariate analysis. In multivariate analysis, DBC1 expression was an independent prognostic predictor for OS (P = .035) and AR expression significantly correlated with RFS (P = .005). CONCLUSION: We demonstrate that the expression of DBC1 and AR are significant prognostic indicators for DLBCL patients, especially for unfavorable non-GCB-type DLBCL.     

外周血NETs、TP53、STAT3表达与弥漫性大B细胞淋巴瘤临床病理及预后的关系分析

摘要 目的：探究外周血中性粒细胞胞外诱捕网（NETs）、TP53、信号转导与转录因子3（STAT3）表达与弥漫性大B细胞淋巴瘤（DLBCL）临床病理及预后的关系。方法：选取2020年3月-2021年12月收治的71例DLBCL患者作为研究对象,抽取患者外周静脉血,采用R-CHOP方案进行治疗,记录患者外周血NETs、TP53、STAT3表达情况并分析DLBCL患者外周血NETs、TP53、STAT3表达与其临床病理及预后的关系。结果：髓细胞组织增生蛋白（MYC）阳性在TP53阳性中的占比显著高于TP53阴性,差异有统计学意义（x²=28.844,P＜0.001）;Hans分型生发中心B细胞（GCB）在STAT3阳性中的占比显著高于STAT3阴性（x²=4.331,P=0.037）,其余差异无统计学意义（P>0.05）;随访截止至2022年6月,随访时长8~28个月,71例患者中共53例缓解DLBCL患者,其余18例为R/R DLBCL患者;NETs阳性、TP53阳性、STAT3阳性患者无进展生存期（PFS）显著低于NETs阴性、TP53阴性、STAT3阴性患者,差异有统计学意义（P<0.05）且NETs阳性、TP53阳性、STAT3阳性患者存活率均低于NETs阴性、TP53阴性、STAT3阴性患者（P<0.05）;单因素分析结果显示Ann Arbor分期、NETs、TP53、STAT3为DLBCL患者的影响因素（P<0.05）;以患者预后情况（R/R DLBCL=1,缓解DLBCL=0）为因变量,将Ann Arbor分期、NETs、TP53、STAT3单因素分析有统计学意义的因素纳入COX回归模型中,结果显示：NETs、TP53、STAT3为DLBCL患者预后的危险因素（P<0.05）。结论：TP53、STAT3表达与DLBCL临床病理存在一定相关性,临床应对DLBCL患者TP53、STAT3表达情况引起重视;NETs、TP53、STAT3表达为DLBCL预后的危险因素,可作为DLBCL患者不良预后的预测指标。     

Clinical significance of cytogenetic aberrations in bone marrow of patients with diffuse large B-cell lymphoma: prognostic significance and relevance to histologic involvement

Background

Although knowledge of the genetics of diffuse large B-cell lymphoma (DLBCL) has been increasing, little is known about the characteristics and prognostic significance of cytogenetic abnormalities and the clinical utility of cytogenetic studies performed on bone marrow (BM) specimens. To investigate the significance of isolated cytogenetic aberrations in the absence of histologic BM involvement, we assessed the implication of cytogenetic staging and prognostic stratification by a retrospective multicenter analysis of newly diagnosed DLBCL patients.

Methods

We analyzed cytogenetic and clinical data from 1585 DLBCL patients whose BM aspirates had been subjected to conventional karyotyping for staging. If available, interphase fluorescence in situ hybridization (FISH) data were also collected from patients.

Results

Histologic BM involvement were found in 259/1585 (16.3%) patients and chromosomal abnormalities were detected in 192 (12.1%) patients (54 patients with single abnormalities and 138 patients with 2 or more abnormalities). Isolated cytogenetic aberrations (2 or more abnormalities) without histologic involvement were found in 21 patients (1.3%). Two or more cytogenetic abnormalities were associated with inferior overall survival (OS) compared with a normal karyotype or single abnormality in both patients with histologic BM involvement (5-year OS, 22.0% vs. 52.7%; P < 0.001) and those without BM involvement (31.8% vs. 66.5%; P < 0.001). This result demonstrated that BM cytogenetic results have a significant prognostic impact that is independent of BM histology. The following abnormalities were most frequently observed: rearrangements involving 14q32, 19q13, 19p13, 1p, 3q27, and 8q24; del(6q); dup(1q); and trisomy 18. In univariate analysis, several specific abnormalities including abnormalities at 16q22-q24, 6p21-p25, 12q22-q24, and -17 were associated with poor prognosis. Multivariate analyses performed for patients who had either chromosomal abnormalities or histologic BM involvement, revealed IPI high risk, ≥ 2 cytogenetic abnormalities, and several specific chromosomal abnormalities, including abnormalities at 19p13, 12q22-q24, 8q24, and 19q13 were significantly associated with a worse prognosis.

Conclusions

We suggest that isolated cytogenetic aberrations can be regarded as BM involvement and cytogenetic evaluation of BM improves staging accuracy along with prognostic information for DLBCL patients.

     

Evaluation of different staging systems and prognostic analysis of nasal-type extranodal NK/T-cell lymphoma based on consistent LVDP chemotherapy regimen

Nasal-type extranodal NK-T-cell lymphoma (ENKTL) is a rare non-Hodgkin lymphoma. The optimal staging system for it remains undefined. In this study, we evaluated different staging systems in 205 patients with nasal-type ENKTL based on a consistent LVDP (L-asparaginase, etoposide, dexamethasone, cisplatin) regimen. All patients were staged by Ann Arbor staging system (AASS) and CA staging system (CASS). Their characteristics, treatment responses, survival outcomes, prognostic factors, and prognostic values of AASS and CASS were analyzed. The median follow-up time was 78 months. All patients received a median 4 cycles of the LVDP chemotherapy. Based on CASS, patients with stages I through IV were more evenly distributed than with AASS, and numbered at 56 (27.3%), 70 (33.2%), 45 (21.9%), and 34 (17.6%), respectively. At the end of therapy, the objective response rate (ORR) was 81.2% for all patients. For all patients, the 5-year progression-free survival (PFS) and overall survival (OS) were 61.6% and 67.8%. According to AASS, the 5-year OS of patients with stages Ⅰ through Ⅳ were 77.9%, 61.2%, 60.0%, and 38.7%, respectively (χ²=20.578, p<0.001). Based on CASS, the 5-year OS of patients with stages Ⅰ to Ⅳ were 89.1%, 65.5%, 58.6%, and 45.4%, respectively (χ²=22.973, p<0.001). In ROC analysis of OS, the area under the curve (AUC) for CASS was 0.70 and 0.64 for AASS. CASS was better in discriminating survival than AASS (p = 0.018). In conclusion, the LVDP regimen is effective for nasal-type ENKTL and the CASS has a better prognostic value in survival analysis than the AASS.     

Primary Adrenal Lymphoma: a Single-Center Experience

Objective: To describe the clinical presentation, biochemistry, imaging features, and treatment outcome of patients with primary adrenal lymphoma (PAL) presenting to a single tertiary care center.Methods: We performed a retrospective analysis of case records of 7 patients diagnosed with PAL between January 2011 and May 2014 at our institution in Mumbai, India.Results: Median age of presentation in our series was 48 years (range, 41 to 60 years), with a male to female ratio of 6:1. Bilateral adrenal involvement was seen in 4 of 7 patients (58%). Adrenal insufficiency (AI) was seen in 3 of the 4 patients with bilateral involvement (75%). Computed tomography showed slight to moderate contrast enhancement of adrenal masses in 4 of 5 patients (80%). Diffuse, large, B-cell lymphoma (DLBCL) was the most common immunophenotype (85%). One patient died due to rapid disease progression even before starting chemotherapy. Six patients were treated with chemotherapy and/or external beam radiotherapy. After 1 year, 2 more patients had died, whereas 4 patients were in remission.Conclusion: PAL should always be considered in differential diagnosis of bilateral adrenal mass with AI. DLBCL is the most common histologic subtype of PAL. Despite treatment, long-term prognosis of PAL remains poor.Abbreviations: AI = adrenal insufficiency B/L = bilateral CT = computed tomography DLBCL = diffuse, large, B-cell lymphoma EBRT = external beam radiotherapy ¹⁸F-FDG PET/CT= ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography PAL = primary adrenal lymphoma T/NK = T cell/natural killer cell     

Imatinib Mesylate for Patients with Recurrent or Metastatic Gastrointestinal Stromal Tumors Expressing KIT: A Decade Experience from Taiwan

PURPOSE: Our preliminary report of imatinib mesylate (IM) in gastrointestinal stromal tumor (GIST) patients detailed a high response rate; however, the long-term result is still unknown. We conducted an analysis of Taiwan advanced inoperable/metastatic GIST patients treated on IM regarding survival, pattern of failure, potential prognostic factors, and mutational status. PATIENTS AND METHODS: From 2001 to 2010, patients with pathologically proven advanced inoperable/metastatic GIST receiving IM were enrolled onto this study. Data on KIT mutational status, measurable tumor size, and other potential prognostic factors were prospectively collected. Patients were followed up for a median of 33.6 months. RESULTS: There were 171 patients (106 men and 65 women) with response rate, and their clinical benefit for IM was 57.3% and 87.1%, respectively. Median progression-free survival (PFS) and overall survival (OS) for these 171 patients are 37.6 and 71.0 months, respectively. Of 171 patients, 120 (70.2%) remained on long-term IM use. Poor performance status, tumor larger than 11.5 cm, primary resistance, and the presence of an exon 9 mutation were independently associated with unfavorable PFS. Regarding OS, poor performance status, primary resistance, and tumor larger than 11.5 cm were three independently unfavorable predictors. CONCLUSIONS: The median PFS and OS of 171 GIST patients are 37.6 and 71.0 months, respectively. Poor performance status, tumor size larger than 11.5 cm, primary resistance, and an exon 9 mutation were independently associated with unfavorable PFS. Regarding OS, poor performance status, primary resistance, and tumor size larger than 11.5 cm were three independent unfavorable predictors.     

The binary presence or absence of lymph node metastasis or extrathyroidal extension is not associated with survival in papillary thyroid cancers: Implications for staging systems

BackgroundThe characteristics of diagnosed papillary thyroid cancer (PTC) have changed over time with the increasing trend of early diagnosis, and the survival impact of conventional prognostic factors such as lymph node metastasis (LNM) and extrathyroidal extension (ETE) is controversial. We investigated PTC prognostic factors for overall survival (OS) and disease specific survival (DSS), focusing on LNM, ETE, and their implications for PTC staging systems.MethodsWe assessed prognostic factors for OS and DSS in a nationwide sample of Korean PTC patients (N = 5192, median follow-up 121 months) using Cox regression. The binary presence or absence of LNM and ETE, as well as other measures of LNM and ETE, were examined for their survival impact. We also evaluated the relative performance of PTC staging systems before and after revising the staging criteria for LNM and ETE.ResultsThe binary presence of LNM or ETE was not a prognostic factor for OS or DSS, nor were other various measures of LNM. However, the extent of ETE as none, microscopic, or gross independently influenced survival (OS hazard ratio for gross vs. none: 3.28, 95% confidence interval (CI) 1.97–5.46; DSS hazard ratio for gross vs. none: 3.75, 95% CI 1.59–8.81). The performance of PTC staging systems improved when the extent of ETE and/or location of LNM were used as staging components.ConclusionThe extent of ETE and/or location of LNM may be better survival indicators than their binary presence or absence, and we propose staging criteria revisions to pertinent staging systems to better reflect the contemporary PTC population.     

Characteristics and outcomes of advanced melanoma patients with complete response and elective discontinuation of first-line anti-programmed death-1 monotherapy: A real-world multicentre observational cohort study

Anti-programmed death-1 (anti-PD1) treatment has significantly improved outcomes of advanced melanoma with a considerable percentage of patients achieving complete response (CR). This real-world study analyzed the feasibility of elective anti-PD1 discontinuation in advanced melanoma patients with CR and evaluated factors related to sustained response. Thirty-five patients with advanced cutaneous or primary unknown melanoma with CR to nivolumab or pembrolizumab from 11 centers were included. Mean age was 66.5 years, and 97.1% had ECOG PS 0–1. 28.6% had ≥3 metastatic sites with 58.8% having M1a-M1b disease; 8.6% had liver and 5.7% had brain metastases. At baseline, 80% had normal LDH, and 85.7% had a neutrophil-to-lymphocyte ratio ≤3. 74.3% of patients had CR confirmed in PET-CT. Median duration of anti-PD1 was 23.4 months (range 1.3–50.5). 24 months after therapy discontinuation, 91.9% of patients were progression-free. Estimated PFS and OS at 36, 48, and 60 months from the start of anti-PD1 were 94.2%, 89.9%, 84.3%, and 97.1%, 93.3%, 93.3%, respectively. Antibiotics use after anti-PD1 discontinuation increased the odds of progression (OR 16.53 [95% CI 1.7, 226.03]). The study confirms the feasibility of elective anti-PD1 discontinuation in advanced melanoma patients with CR and favorable prognostic factors at baseline.     

Analysis of the efficacy,safety and survival factors of stereotactic body radiation therapy in patients with recurrence of pancreatic cancer

Objective: This study aims to evaluate the efficacy and safety of stereotactic body radiation therapy (SBRT) using Cyber Knife (CK) in the treatment of patients with recurrent pancreatic cancer after surgery, and analyze its survival-related factors. Methods: The primary endpoint was freedom from local progression (FFLP) and local control (LC) rate after CK. The secondary endpoints were overall survival (OS), progression-free survival (PFS), symptom relief and toxicities. Receiver operating characteristic (ROC) curves were used to determine the optimal cut-off values of inflammatory composite indicators NLR, PLR, SII and PNI. The prognostic factors that affected these patients were analyzed by univariate and multivariate analysis, respectively. Results: A total of 27 patients were enrolled. Median local recurrence disease free interval（DFI）was 11.3 (1.3-30.6) months, LC was 81.5% and 37.0% at 6 and 12 months, respectively. Median PFS was 7.1 (1.3-27.1) months. Median OS was 11.3 (1.3-30.6) months. Symptom alleviation was observed in 16 of 17 patients (94.1%) within 2 weeks after CK. Subsequent chemotherapy, CA199≥50% decrease after CK were independent prognostic factors for OS (all P <0.05). Conclusion: SBRT is a safe and effective treatment approach for recurrent pancreatic adenocarcinoma. Encouraging local control rate, low toxicity, and effective symptom relief suggests the vital role of CK in the treatment of these patients. This clinical application needs to be further studied in the combination of CK and multimodal therapy.     

Blood Lymphocyte-to-Monocyte Ratio Identifies High-Risk Patients in Diffuse Large B-Cell Lymphoma Treated with R-CHOP

Background

Recent research has shown a correlation between immune microenvironment and lymphoma biology. This study aims to investigate the prognostic significance of the immunologically relevant lymphocyte-to-monocyte ratio (LMR), in diffuse large B-cell lymphoma (DLBCL) in the rituximab era.

Methodology/Principal Findings

We analyzed retrospective data from 438 newly diagnosed DLBCL patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy. We randomly selected 200 patients (training set) to generate a cutoff value for LMR by receiver operating characteristic (ROC) curve analysis. LMR was then analyzed in a testing set (n = 238) and in all patients (n = 438) for validation. The LMR cutoff value for survival analysis determined by ROC curve in the training set was 2.6. Patients with low LMR tended to have more adverse clinical characteristics. Low LMR at diagnosis was associated with worse survival in DLBCL, and could also identify high-risk patients in the low-risk IPI category. Multivariate analysis identified LMR as an independent prognostic factor of survival in the testing set and in all patients.

Conclusions/Significance

Baseline LMR, a surrogate biomarker of the immune microenvironment, is an effective prognostic factor in DLBCL patients treated with R-CHOP therapy. Future prospective studies are required to confirm our findings.     

乳腺恶性血液病的病理类型、临床特点及生存分析

目的:探讨乳腺恶性血液病的病理分型、患者的临床特征及预后。方法:回顾性分析2014年1月至2019年1月空军军医大学西京医院收治的33例乳腺恶性血液病患者的病理分型、临床特征及预后。结果:33例患者中,32例为女性,1例为男性,平均年龄为45.5岁(12-78岁)。经病理确诊29例(29/33,87.9%)为非霍奇金淋巴瘤,其中弥漫大B细胞淋巴瘤(18/29,62.1%)最为常见,其次是NK/T细胞淋巴瘤(3/29,10.3%),B淋巴母细胞白血病/淋巴瘤(2/29,6.8%),而伯基特淋巴瘤、滤泡淋巴瘤、原发皮肤间变大细胞淋巴瘤各1例(1/29,3.4%),其余3例未进一步分型。此外,1例(1/33,3.0%)霍奇金淋巴瘤,3例(3/33,9.1%)急性白血病复发累及乳腺。原发性乳腺恶性血液病为19例(57.6%),继发性为14例(42.4%),病变主要累及右侧乳腺(18例,54.5%),其次为左侧(10例,30.3%),双侧均累及的为少数(5例,15.2%)。19例原发性乳腺恶性血液病均为淋巴瘤,与14例继发性乳腺恶性血液病相比,其血小板计数明显升高(P=0.004),β2-MG显著降低(P=0.049),B症状少(P=0.017),Ann Arbor分期主要为Ⅰ-Ⅱ期(P<0.01),骨髓受累少(P<0.01)等特点。生存分析提示原发性乳腺恶性血液病患者比继发性患者生存期更长(HR=9.846,P=0.002)。恶性血液病累及骨髓可导致生存期显著缩短(HR=6.434,P<0.01)。结论:乳腺恶性血液病患者以中年女性为主,原发性乳腺恶性血液病比继发性发病率高(分别为57.5%和42.5%),最常见的病理类型为弥漫大B细胞淋巴瘤,病变主要累及右侧乳腺。与继发性乳腺恶性血液病相比,原发性乳腺恶性血液病患者具有血小板计数相对更高,β2-MG水平更低,往往不伴B症状,Ann Arbor分期主要为Ⅰ-Ⅱ期,骨髓不受累,且生存期显著延长等特点。此外,恶性血液病累及骨髓提示预后不良。     

A20 Mutation Is Not a Prognostic Marker for Activated B-Cell-Like Diffuse Large B-Cell Lymphoma

Background

Constitutive activation of nuclear factor κB (NF-κB) is a hallmark of activated B-cell-like diffuse large B-cell lymphoma (ABC-DLBCL). Mutations in the A20 gene activate NF-κB, but the prognostic value of A20 mutations in ABC-DLBLC is unclear.

Purpose

To investigate the prognostic value of A20 mutation in ABC-DLBCL patients.

Methods

The somatic mutation of A20 was investigated in 68 de novo ABC-DLBCLs by PCR/sequencing. The Kaplan-Meier method was used to estimate median overall survival (OS) and progression-free survival (PFS).

Results

The A20 mutation rate in ABC-DLBCL patients was 29.4%. Complete remission rates were 35% and 45.8% in patients with and without A20 mutations, respectively (P = 0.410). In patients with and without A20 mutations, the median OS was 24.0 and 30.6 months, respectively (P = 0.58), and the median PFS was 15 and 17.4 months, respectively (P = 0.52). None of the differences between the patient groups were significant.

Conclusions

Our findings suggested that the A20 mutation is a frequent event in ABC-DLBCLs. However, there was no significant difference in PFS and OS in patients with or without A20 mutations. Further study is required to completely exclude A20 somatic mutation as a prognostic marker in the ABC subtype of DLBLC.     

Negative Impact of Skeletal Muscle Loss after Systemic Chemotherapy in Patients with Unresectable Colorectal Cancer

Background

Skeletal muscle depletion (sarcopenia) is closely associated with limited physical ability and high mortality. This study evaluated the prognostic significance of skeletal muscle status before and after chemotherapy in patients with unresectable colorectal cancer (CRC).

Methods

We conducted a retrospective analysis of 215 consecutive patients with unresectable CRC who underwent systemic chemotherapy. Skeletal muscle cross-sectional area was measured by computed tomography. We evaluated the prognostic value of skeletal muscle mass before chemotherapy and the rate of skeletal muscle change in cross-sectional area after chemotherapy.

Results

One-hundred-eighty-two patients met our inclusion criteria. There were no significant differences in progression-free survival (PFS) or overall survival (OS) associated with skeletal muscle mass before chemotherapy. However, 22 patients with skeletal muscle loss (>5%) after chemotherapy showed significantly shorter PFS and OS compared with those without skeletal muscle loss (PFS, log-rank p = 0.029; OS, log-rank p = 0.009). Multivariate Cox regression analysis revealed that skeletal muscle loss after chemotherapy (hazard ratio, 2.079; 95% confidence interval, 1.194–3.619; p = 0.010) was independently associated with OS.

Conclusions

Skeletal muscle loss after chemotherapy was an independent, negative prognostic factor in unresectable CRC.     

肝癌患者经系统治疗后甲胎蛋白变化对预后的影响

目的:探讨肝癌患者经系统治疗后甲胎蛋白(AFP)变化对患者预后的影响。方法:对53例肝癌患者于入院后和系统治疗后分别于不同时间点测定血清AFP值后,将入院时AFP值作为基线,以变化50%作为标准分组,并进行无疾病进展生存时间(PFS)和总生存时间(OS)分析。结果:9例患者血清AFP值下降超过50%(A组),28例患者AFP值升高超过50%(B组),而AFP值变化小于50%(C组)的为16例。和C组相比,A组患者PFS明显延长(P<0.05),B组PFS明显缩短(P<0.05)。B组OS短于C组(P<0.01),而A组和C组间OS无明显差别(P>0.05)。结论:肝癌系统治疗前后的AFP值变化可作为临床上预后判断的标志之一。