Prognostic significance of the systemic immune-inflammation index in patients with extranodal natural killer/T-cell lymphoma.

Background: The systemic immune-inflammation index (SII) is based on the neutrophil, platelet, and lymphocyte counts, and has been identified as a prognostic marker in multiple types of cancer. However, the potential value of the SII for predicting survival outcomes in patients with extranodal natural killer/T-cell lymphoma (ENKTCL) has not been investigated thus far. Method: This study included 382 patients with ENKTCL treated with asparaginase-base regimens from 2021 to 2017 in West China Hospital (Chengdu, China). Clinical and demographic variables, as well as the prognostic value of the SII, were analyzed using Cox proportional hazards regression analysis. Results: The complete and objective response rates were 55.8% and 74.9%, respectively. Patients with high SII were associated with a lower rate of complete response, higher rate of B symptoms, and serum lactate dehydrogenase levels above or equal to the upper limits of normal (p < 0.01). Patients with low SII were linked to better overall survival and progression-free survival than those with high SII (p < 0.01). Patients with early-stage disease or prognostic model for natural killer lymphoma with Epstein-Barr virus, defined as the low-risk group, could be further stratified according to the SII (p < 0.01). Negative prognostic factors were determined using the Cox proportional hazards regression analysis, which identified four variables: Eastern Cooperative Oncology Group performance status score ≥2, Stage III/IV disease, positivity for Epstein-Barr virus DNA in plasma, and high SII. Predictive nomograms for the prediction of 3- and 5-year overall survival, as well as progression-free survival, were constructed based on those four variables. The nomograms demonstrated favorable discriminating power. Conclusion: The SII is a novel prognostic marker for ENKTCL, which may be used for the prediction of poorer survival in low-risk patients.

Effect of genetic liability to migraine and its subtypes on breast cancer: a mendelian randomization study.

BACKGROUND: The relationship between migraine and breast cancer risk has generated conflicting findings. We attempted to assess the association between migraine and breast cancer risk using Mendelian randomization (MR) analysis. METHODS: We selected genetic instruments associated with migraine from a recently published genome-wide association studies (GWAS). Inverse variant weighted (IVW) analysis was adopted as the main method, and we also performed the weighted-median method and the MR‒Egger, MR pleiotropy residual sum and outlier (MR-PRESSO), and MR Robust Adjusted Profile Score (MR-RAPS) methods as supplements. RESULTS: Our MR suggested that any migraine (AM) was a risk factor for overall breast cancer (IVW: odds ratio (OR) = 1.072, 95% confidence intervals (CI) = 1.035-1.110, P = 8.78 × 10- 5, false discovery rate (FDR) = 7.36 × 10- 4) and estrogen receptor-positive (ER+) breast cancer (IVW: OR = 1.066, 95% CI = 1.023-1.111, P = 0.0024; FDR = 0.0108) but not estrogen receptor-negative (ER-) breast cancer. In its subtype analysis, women with a history of migraine without aura (MO) had an increased risk of ER- breast cancer (IVW: OR = 1.089, 95% CI = 1.019-1.163, P = 0.0118, FDR = 0.0354), and MO was suggestively associated with the risk of overall breast cancer (FDR > 0.05 and IVW P < 0.05). No significant heterogeneity or horizontal pleiotropy was found in the sensitivity analysis. CONCLUSION: This study suggested that women with AM have an increased risk of overall breast cancer and ER + breast cancer. MO was suggestively associated with the risk of overall breast cancer and ER- breast cancer.

The effect of cyberbullying victimization and traditional bullying victimization on suicidal ideation among Chinese female college students: The role of rumination and insomnia.

BACKGROUND: The issue of college student suicide has emerged as a significant global public health concern. To date, there has been a lack of extensive research on the effects of distinct forms of bullying victimization (traditional bullying victimization and cyberbullying victimization) on suicidal ideation, as well as the differences between them. The present study aimed to investigate the relationship between two forms of bullying victimization and suicidal ideation among female college students, while also considering the potential mediating effects of rumination and insomnia. METHODS: A total of 2106 female college students from Southern China participated in this study. The participants had a mean age of 19.83 years (SD = 1.04 years). Participants completed the MINI-C questionnaire, School Bullying Behavior Questionnaire, Cyberbullying Inventory (CBI), Ruminative Responses Scale (RRS), and Insomnia Severity Index (ISI). The mediation models were conducted using Model 4 and Model 6 of the Process macro program in SPSS. RESULTS: The results showed that (1) the mediating effect of rumination in the relationship between different forms of bullying victimization and suicidal ideation was significant; (2) The mediating effect of insomnia in the relationship between traditional bullying victimization and suicidal ideation was not significant; the mediating effect between cyberbullying victimization and suicidal ideation was significant. (3) The chain mediating effect of rumination and insomnia in the relationship between different forms of bullying victimization and suicidal ideation were both significant. CONCLUSION: This study endeavor represents the first attempt to investigate the relationship between two forms of bullying victimization and suicidal ideation.

Olfactory response is a potential sign of consciousness: electroencephalogram findings.

Objective: This study aimed to explore whether olfactory response can be a sign of consciousness and represent higher cognitive processing in patients with disorders of consciousness (DoC) using clinical and electroencephalogram data. Methods: Twenty-eight patients with DoC [13 vegetative states (VS)/unresponsive wakefulness syndrome (UWS) and 15 minimally conscious states (MCS)] were divided into two groups: the presence of olfactory response (ORES) group and the absence of olfactory response (N-ORES) group according to behavioral signs from different odors, i.e., vanillin, decanoic acid, and blank stimuli. We recorded an olfactory task-related electroencephalogram (EEG) and analyzed the relative power and functional connectivity at the whole-brain level in patients with DoC and healthy controls (HCs). After three months, the outcomes of DoC patients were followed up using the coma recovery scale-revised (CRS-R). Results: A significant relationship was found between olfactory responses and the level of consciousness (χ2(1) = 6.892, p = 0.020). For olfactory EEG, N-ORES patients showed higher theta functional connectivity than ORES patients after stimulation with vanillin (p = 0.029; p = 0.027). Patients with N-ORES showed lower alpha and beta relative powers than HCs at the group level (p = 0.019; p = 0.033). After three months, 62.5% (10/16) of the ORES patients recovered consciousness compared to 16.7% (2/12) in the N-ORES group. The presence of olfactory response was significantly associated with an improvement in consciousness (χ2(1) = 5.882, p = 0.023). Conclusion: Olfactory responses should be considered signs of consciousness. The differences in olfactory processing between DoC patients with and without olfactory responses may be a way to explore the neural correlates of olfactory consciousness in these patients. The olfactory response may help in the assessment of consciousness and may contribute to therapeutic orientation.

Multiple sclerosis and breast cancer risk: a meta-analysis of observational and Mendelian randomization studies.

Background: Several observational studies have explored the relationships between multiple sclerosis (MS) and breast cancer; however, whether an association exists remains unknown. Methods: We conducted a meta-analysis of observational studies and Mendelian randomization (MR) based on genetic variants to identify the relationship between MS and breast cancer. The observational studies were searched from PubMed, Embase, Web of Science, and Scopus to assess the relationship between MS and breast cancer from inception to 07 Nov 2022. Moreover, we explored the association between genetically pre-disposed MS and breast cancer risk based on an MR study. The summary analysis for MS from two separate databases [International Multiple Sclerosis Genetics Consortium (IMSGC), FinnGen] and the summary analysis for breast cancer from Breast Cancer Association Consortium. Results: Fifteen cohort studies involving 173,565 female MS patients were included in this meta-analysis. The correlation between MS and breast cancer was not statistically significant [relative ratio (RR) = 1.08, 95% confidence interval (CI) = 0.99-1.17]. In the MR analysis, we did not observe causal associations of genetically determined MS with breast cancer and its subtypes from both the IMSGC and FinnGen datasets. Conclusion: The meta-analysis of observational and MR based on genetic variants does not support the correlation between MS and breast cancer.

Effects of 10 Hz individualized repetitive transcranial magnetic stimulation on patients with disorders of consciousness: a study protocol for an exploratory double-blind crossover randomized sham-controlled trial.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS), as a non-invasive brain stimulation technique, has shown potentials for consciousness recovery of patients with disorders of consciousness (DoC), as, to a certain extent, it is effective in regulating the excitability of central nervous system. However, it is difficult to achieve satisfactory effect with "one size fits all" rTMS treatment due to different clinical conditions of patients. There is an urgent need to develop individualized strategy to improve the effectiveness of rTMS on patients with DoC. METHODS: Our protocol is a randomized double-blind sham-controlled crossover trial that includes 30 DoC patients. Each patient will received 20 sessions, in which 10 sessions will be rTMS-active stimulus, and the other 10 sessions will be sham stimulus, separated by no less than 10 days' washout period. The rTMS-active will include 10 Hz rTMS over the individualized-targeted selection area for each patient according to the different insult regions of the brain. Coma Recovery Scale-Revised (CRS-R) will be used as primary outcome at baseline, after the first stage of stimulation, at the end of the washout period, and after the second stage of stimulation. Secondary outcomes will be measured at the same time, including efficiency, relative spectral power, and functional connectivity of high-density electroencephalograph (EEG). Adverse events will be recorded during the study. DISCUSSION: rTMS has obtained grade A evidence in treating patients with several central nervous system diseases, and there has been some evidence showing partial improvement on level of consciousness in DoC patients. However, the effectiveness of rTMS in DoC is only 30~36%, mostly due to the non-specific target selection. In this protocol, we present a double-blind crossover randomized sham-controlled trial based on the individualized-targeted selection strategy that aims to study the effectiveness of rTMS therapy for DoC, and the result may provide new insights to non-invasive brain stimulation. TRIAL REGISTRATION: ClinicalTrials.gov : NCT05187000. Registered on January 10, 2022.

A neutrophil/lymphocyte Ratio as a Significant Predictor for Patients with low-risk and early-stage Extranodal NK-T-cell Lymphoma.

Purpose: The neutrophil/lymphocyte ratio (NLR) is a novel prognostic marker in several malignancies, whereas its function in patients with early-stage extranodal NK-T-cell lymphoma (ENKTL) hasn't been explored. Therefore, we expolored the predictive value of NLR for early-stage ENKTL in this study. Methods: We evaluated the prognostic value of NLR in 132 patients with early-stage ENKTL based on L-asparaginase-containing regimens. Their characteristics, treatment responses, survival outcomes, prognostic factors, and the prognostic value of NLR were analyzed. Results: All patients were followed up for median 54 months. The optimal NLR cutoff value was 3.77 by receiver operating curve(ROC). For all patients, the complete response (CR) and the overall response rate (ORR) were 74.2% and 85.6%. Patients with NLR < 3.77 had higher CR and ORR than patients with NLR ≥ 3.77(CR, 81% vs. 53.1%; ORR, 90% vs. 71.9%). For all patients, the 3-year overall survival (OS) and progression-free survival (PFS) based on L-asparaginase-containing chemotherapy were 80.4% and 76%. Patients with NLR < 3.77 had better survival outcomes than patients with NLR ≥ 3.77(3-year OS, 86.9% vs. 60.3%, p = 0.002; 3-year PFS, 81.8% vs. 54.5%, p = 0.001). By univariate and multivariate analyses, NLR ≥ 3.77 was an independent poor prognostic factor for both OS and PFS. Additionally, NLR ≥ 3.77 was associated with poor survival outcomes in patients with low-risk International Prognostic Index (IPI) and Prognostic Index of Natural Killer lymphoma with Epstein-Barr virus (PINK-E). Conclusion: A high NLR is a poor prognostic marker of survival in patients with early-stage ENKTL, and could be applied to risk-stratify for low-risk patients.

Repetitive transcranial magnetic stimulation over the posterior parietal cortex improves functional recovery in nonresponsive patients: A crossover, randomized, double-blind, sham-controlled study.

Background: Recent studies have shown that patients with disorders of consciousness (DoC) can benefit from repetitive transcranial magnetic stimulation (rTMS) therapy. The posterior parietal cortex (PPC) is becoming increasingly important in neuroscience research and clinical treatment for DoC as it plays a crucial role in the formation of human consciousness. However, the effect of rTMS on the PPC in improving consciousness recovery remains to be studied. Method: We conducted a crossover, randomized, double-blind, sham-controlled clinical study to assess the efficacy and safety of 10 Hz rTMS over the left PPC in unresponsive patients. Twenty patients with unresponsive wakefulness syndrome were recruited. The participants were randomly divided into two groups: one group received active rTMS treatment for 10 consecutive days (n = 10) and the other group received sham treatment for the same period (n = 10). After a 10-day washout period, the groups crossed over and received the opposite treatment. The rTMS protocol involved the delivery of 2000 pulses/day at a frequency of 10 Hz, targeting the left PPC (P3 electrode sites) at 90% of the resting motor threshold. The primary outcome measure was the JFK Coma Recovery Scele-Revised (CRS-R), and evaluations were conducted blindly. EEG power spectrum assessments were also conducted simultaneously before and after each stage of the intervention. Result: rTMS-active treatment resulted in a significant improvement in the CRS-R total score (F = 8.443, p = 0.009) and the relative alpha power (F = 11.166, p = 0.004) compared to sham treatment. Furthermore, 8 out of 20 patients classified as rTMS responders showed improvement and evolved to a minimally conscious state (MCS) as a result of active rTMS. The relative alpha power also significantly improved in responders (F = 26.372, p = 0.002) but not in non-responders (F = 0.704, p = 0.421). No adverse effects related to rTMS were reported in the study. Conclusions: This study suggests that 10 Hz rTMS over the left PPC can significantly improve functional recovery in unresponsive patients with DoC, with no reported side effects. Clinical trial registration: www.ClinicalTrials.gov, identifier: NCT05187000.

Radiomics-guided checkpoint inhibitor immunotherapy for precision medicine in cancer: A review for clinicians.

Immunotherapy using immune checkpoint inhibitors (ICIs) is a breakthrough in oncology development and has been applied to multiple solid tumors. However, unlike traditional cancer treatment approaches, immune checkpoint inhibitors (ICIs) initiate indirect cytotoxicity by generating inflammation, which causes enlargement of the lesion in some cases. Therefore, rather than declaring progressive disease (PD) immediately, confirmation upon follow-up radiological evaluation after four-eight weeks is suggested according to immune-related Response Evaluation Criteria in Solid Tumors (ir-RECIST). Given the difficulty for clinicians to immediately distinguish pseudoprogression from true disease progression, we need novel tools to assist in this field. Radiomics, an innovative data analysis technique that quantifies tumor characteristics through high-throughput extraction of quantitative features from images, can enable the detection of additional information from early imaging. This review will summarize the recent advances in radiomics concerning immunotherapy. Notably, we will discuss the potential of applying radiomics to differentiate pseudoprogression from PD to avoid condition exacerbation during confirmatory periods. We also review the applications of radiomics in hyperprogression, immune-related biomarkers, efficacy, and immune-related adverse events (irAEs). We found that radiomics has shown promising results in precision cancer immunotherapy with early detection in noninvasive ways.

Comparison of the clinical efficacies of two L-asparaginase-based chemotherapy regimens for newly diagnosed nasal-type extranodal NK/T-cell lymphoma.

BACKGROUND: Nasal-type extranodal natural killer (NK)/T cell lymphoma (ENKTL) is a rare and aggressive type of lymphoma. The optimal chemotherapy regimen for ENKTL has not yet been established. In this study, we compared the LVDP (L-asparaginase, etoposide, dexamethasone, and cisplatin) and GLIDE (gemcitabine, L-asparaginase, ifosfamide, dexamethasone, and etoposide) chemotherapy regimens for the treatment of ENKTL. METHODS: A total of 267 patients with newly diagnosed ENKTL were included in this retrospective study. Propensity score matching (PSM) was used to adjust for confounders between the LVDP and GLIDE groups. Treatment responses, survival outcomes, and toxicities between the two groups were compared before and after PSM. RESULTS: At the end of therapy, the objective response rate (ORR) and complete response (CR) were 83.5% and 62.2%, respectively, for all patients. The ORR and CR were 85.5% and 62.2% for the LVDP group compared with 79.3% and 62.2% for the GLIDE group, respectively, and no differences between the two groups were found (ORR, p = 0.212; CR, p = 0.996). With a median 71 months follow-up, the 5-year progression-free survival (PFS) and overall survival (OS) rates were 64.3% and 68.5%, respectively. The 5-year PFS and OS were 65.6% and 70.1% for the LVDP group compared with 61.6% and 64.6% for the GLIDE group, respectively (PFS, p = 0.478; OS, p = 0162). After PSM, no significant differences in short-term efficacy (ORR, p = 0.696; CR, p = 0.264) or long-term efficacy (PFS, p = 0.794; OS, p = 0.867) between the two groups were identified. However, treatment-related toxicities were milder in the LVDP group compared to the GLIDE group, even after adjusting for confounders via PSM. CONCLUSION: In conclusion, both LVDP and GLIDE regimens are effective for the treatment of ENKTL. However, the LVDP regimen is safer than the GLIDE regimen, with milder treatment-related toxicities. Therefore, the LVDP regimen could be a preferable option for patients with ENKTL.

Cybervictimization and non-suicidal self-injury among Chinese adolescents: The effect of depression and school connectedness.

Cybervictimization has been shown in many studies to be a risk factor for adolescent non-suicidal self-injurious behavior (NSSI). In this study we tested the roles of depression and school connectedness in this association. The Integrative Model of NSSI, Emotion Regulation and Interpersonal Relationship Model of NSSI, and Integrative Model of Social Media and Suicide provided the conceptual framework for the study. A sample of 1106 adolescents (M age = 13.17; SD = 0.69; 51.78% girls) completed anonymous questionnaires in their classrooms. The results of structural equation modeling showed that the positive association between cybervictimization and adolescent NSSI was mediated by depression. Moreover, this indirect link was stronger for adolescents with low vs. high school connectedness. The results have implications for intervention programs aimed at reducing NSSI among adolescents.

A controlling nutritional status score is an independent predictor for patients with newly diagnosed nasal-type extranodal NK/T-cell lymphoma based on asparaginase-containing regimens.

BACKGROUND: The controlling nutritional status (CONUT) score is a nutritional index that combines serum albumin, total cholesterol, and lymphocyte counts. The potential value of CONUT score for predicting clinical outcomes in patients with nasal-type extranodal NK/T-cell lymphoma (ENKTL) has not been explored. METHODS: This study included 374 ENKTL patients treated with asparaginase-containing regimens from September 2012 to September 2017. Clinical characteristics, treatment efficacy, prognostic factors, and the predictive value of CONUT score were analyzed. RESULTS: The complete response (CR) and overall response rate (ORR) were 54.8% and 74.6%, respectively. Patients with CONUT scores <2 had higher CR and ORR compared to patients with scores ≥2 (69.1% vs. 48.9% for CR, p = 0.001; 90.0% vs. 74.6% for ORR, p < 0.001). The 5-year overall survival (OS) and progression-free survival (PFS) rates were 61.9% and 57.3%, respectively. Patients with CONUT scores <2 had better survival outcomes than those with scores ≥2 (5-year OS, 76.1% vs. 56.0%, p < 0.001; 5-year PFS, 74.4% vs. 50.1%, p < 0.001). CONUT score ≥2 was identified as an independent poor prognostic factor for both OS and PFS. A CONUT score ≥2 was also associated with poorer survival outcomes in low-risk ENKTL patients. CONCLUSION: A CONUT score ≥2 is a prognostic marker for poor survival in patients with ENKTL and could be used to stratify risk in low-risk patients.

Central nervous system involvement at initial diagnosis of extranodal NK/T-cell lymphoma: a retrospective study of a consecutive 12-year case series.

Patients with central nervous system (CNS) involvement at initial diagnosis of extranodal NK/T-cell lymphoma (ENKTL) are exceedingly rare, and the clinicopathologic features of CNS involvement have not been well characterized. In this study, we reviewed 662 patients with ENKTL from August 2008 to September 2019. Their clinical and pathological features, treatments, and survival outcomes were analyzed. The median follow-up time was 72 months. Nine of 662 (1.4%) patients were diagnosed with CNS involvement. Among them, the median age was 37 years, and seven patients were male. All patients had positive EBV-DNA, and three patients were asymptomatic at the time of diagnosis with CNS involvement. Common extranodal involved sites included bone, paranasal sinuses, breast, kidney, adrenal gland, and bone marrow. All patients were positive for cytoplasmic CD3ε, cytotoxic granule proteins, and EBER and negative for CD20. All patients received intrathecal chemotherapy and at least one cycle of systemic chemotherapy. Seven patients had died and two were still alive by the last follow-up. The median overall survival (OS) in patients with CNS involvement at initial diagnosis of ENKTL was 9 months, and the 1-year OS was 44.4%. Five patients achieved a complete response after asparaginase-based chemotherapy; two were still alive, one died of systemic progression, one died of ENKTL-associated hemophagocytic syndrome, and one died of treatment-related infections. In conclusion, CNS involvement at initial diagnosis of ENKTL is extremely rare with poor prognosis. There is no standard treatment, and asparaginase-based chemotherapy combined with intrathecal chemotherapy might yield good efficacy.

The relationship between major life events and non-suicidal self-injury among college students: the effect of rumination and body image.

Background: Non-suicidal self-injury (NSSI) poses a growing risk to public health worldwide. While numerous studies have identified major life events as key risk factors for NSSI, the mechanisms by which emotional and cognitive problems mediate or moderate this relationship remain unclear. To enhance the understanding of this field, we will draw upon the cascade theory of self-injury and the benefits and barriers model, to examine the relationship between major life events and NSSI, as well as the effect of rumination and body image. Methods: A sample of 2,717 college students (Mage = 19.81 years; SD = 1.09) participated in this study and anonymously completed the questionnaires. The moderated mediation model were conducted using Model 4 and Model 15 of the Process macro program in SPSS. Results: The results showed that rumination mediated the positive relationship between major life events and NSSI. Furthermore, body image was found to moderate both the relationship between major life events and NSSI, as well as the relationship between rumination and NSSI. Conclusion: The current findings suggest that rumination is an important mediator in the relationship between major life events and NSSI among college students. Teachers, parents, and researchers should recognize the important role of body image self-perceptions of college students and actively promote a healthy and accurate body image.

Nomograms to predict progression of disease within 24 months in patients with localized natural killer/T-cell lymphoma.

Aims: Progression of disease within 24 months (POD24) is associated with poor survival in some subtypes of lymphoma.The aim is to identify high-risk patients with localized extranodal natural killer/T-cell lymphoma (ENKTL) and to define clinical factors associated with the risk of early recurrence after antitumor treatment. Methods: The authors retrospectively analyzed 330 cases with localized ENKTL, of which 89 experienced POD24. Results: The 5-year overall survival of the POD24 group was extremely inferior to that of the non-POD24 group. Risk factors for POD24 were Eastern Cooperative Oncology Group performance status ≥2, response evaluation (non-complete remission) after first-line treatment and elevated lactate dehydrogenase concentrations. Also, higher Epstein-Barr virus DNA titer was related to POD24. Based on these data with or without the availability of Epstein-Barr virus DNA, the authors conducted two nomograms to predict POD24, which showed good accuracy with high C statistics. Conclusion: The results showed that POD24 could serve as a marker to identify patients whose medical needs were unmet in ENKTL.

Is frontoparietal electroencephalogram activity related to the level of functional disability in patients emerging from a minimally conscious state? A preliminary study.

Objective: When regaining consciousness, patients who emerge from a minimally conscious state (EMCS) present with different levels of functional disability, which pose great challenges for treatment. This study investigated the frontoparietal activity in EMCS patients and its effects on functional disability. Materials and methods: In this preliminary study, 12 EMCS patients and 12 healthy controls were recruited. We recorded a resting-state scalp electroencephalogram (EEG) for at least 5 min for each participant. Each patient was assessed using the disability rating scale (DRS) to determine the level of functional disability. We analyzed the EEG power spectral density and sensor-level functional connectivity in relation to the patient's functional disability. Results: In the frontoparietal region, EMCS patients demonstrated lower relative beta power (P < 0.01) and higher weighted phase lag index (wPLI) values in the theta (P < 0.01) and gamma (P < 0.01) bands than healthy controls. The frontoparietal theta wPLI values of EMCS patients were positively correlated with the DRS scores (r s = 0.629, P = 0.029). At the whole-brain level, EMCS patients only had higher wPLI values in the theta band (P < 0.01) than healthy controls. The whole-brain theta wPLI values of EMCS patients were also positively correlated with the DRS scores (r s = 0.650, P = 0.022). No significant difference in the power and connectivity between the frontoparietal region and the whole brain in EMCS patients was observed. Conclusion: EMCS patients still experience neural dysfunction, especially in the frontoparietal region. However, the theta connectivity in the frontoparietal region did not increase specifically. At the level of the whole brain, the same shift could also be seen. Theta functional connectivity in the whole brain may underlie different levels of functional disability.

18F-FDG PET/CT Plays a Limited Role in Replacing Bone Marrow Biopsy for Newly Diagnosed Advanced-Stage Patients With Extranodal Natural Killer/T-Cell Lymphoma.

Purpose: The role of 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) in evaluating bone marrow (BM) involvement (BMI) among patients with extranodal natural killer/T-cell lymphoma (ENKTL) is poorly understood. This study investigated whether PET/CT could replace bone marrow biopsy (BMB) in treatment-naive ENKTL patients. Methods: Newly diagnosed ENKTL patients (n = 356) who received BMB and PET/CT to evaluate BMI at the time of diagnosis were retrospectively reviewed at West China Hospital between August 2008 and January 2020. The BMI diagnosis was confirmed using BM histology. Clinical characteristics, survival outcomes, and prognostic indicators were summarized and analyzed. Results: The cohort included 356 cases, of whom 261 were diagnosed with early-stage and 95 with advanced-stage ENKTL by PET/CT before initial treatment. No early-stage patients were identified with BMI by either BMB or PET/CT. Among the advanced-stage patients, 26 were BMB positive, and 12 of 22 patients (54.5%) with positive PET/BM results were also BMB positive. The sensitivity and specificity of PET/CT to detect BMI were 46% and 97%, respectively. The progression-free survival (PFS) and overall survival (OS) of PET/BM-negative patients were markedly longer (p = 0.010 and p = 0.001 for PFS and OS, respectively), which was consistent with the results of the BMB (p = 0.000 for both PFS and OS). Conclusion: Although 18F-FDG PET/CT showed the potential to replace BMB in the initial staging of early-stage ENKTL patients, baseline PET/CT cannot provide an accurate BMI evaluation for advanced-stage patients. A prospective study is required to confirm the diagnostic performance of BMI identification by PET/CT, along with targeted BMB and MRI for advanced-stage patients.

Lymphoma-associated hemophagocytic syndrome: a retrospective study from a single center.

Lymphoma-associated hemophagocytic syndrome (LAHS) is a rare and life-threatening clinical syndrome with rapidly deteriorating health and high mortality. We retrospectively analyzed clinical features and prognostic factors from 117 patients diagnosed with LAHS. The cumulative incidence rate of LAHS was 4.0% (117/2906). Patients were classified into B-cell LAHS (B-LAHS, n = 22) and T/natural killer (NK)-cell LAHS (T/NK-LAHS, n = 95) groups. Patients with T/NK-LAHS were younger and had lower neutrophil counts and fibrinogen values, higher LDH and transaminase levels, and were more likely to develop hemophagocytic syndrome (HPS) during the clinical course than those with B-LAHS. The median survival time for the entire cohort was 57 days, and for the T/NK-LAHS and B-LAHS groups, it was 52 and 154 days, respectively, after the diagnosis of LAHS. Patients with B-LAHS had superior 1-year OS (p = 0.003, 36.4% versus 14.5%) compared with those with T/NK-LAHS. Prognostic factor analysis revealed that elevated LDH levels (LDH > 1000 IU/L) (p = 0.004), T/NK-cell lineage (p < 0.001) and HPS onset at relapse (p = 0.001) were strongly associated with early death. For patients diagnosed with T/NK-LAHS, in addition to LDH levels and HPS onset status, high EBV-DNA copies (≥4,450 copies/mL) (p = 0.016) were also related to poor prognosis of T/NK-LAHS.

The value of prognostic nutritional index in nasal-type, extranodal natural killer/T-cell lymphoma.

Extranodal natural killer/T-cell lymphoma (ENKTL) is an aggressive disorder with heterogeneous clinical characteristics and poor prognosis. The combined value of baseline serum albumin level and absolute peripheral lymphocyte count showed prognostic information in a variety of malignancies, but its evidence is limited in ENKTL. The purpose of this study is to evaluate the impact of prognostic nutritional index (PNI) in ENKTL, and to provide some nutritionally and immunologically relevant information for better risk stratification. We conducted a retrospective study in 533 patients newly diagnosed with ENKTL. The PNI was calculated as albumin (g/L) + 5 × lymphocyte count (109/L). The optimal cutoff values for serum albumin and lymphocyte count were 40.6 g/L and 1.18 × 109/L, respectively, and 47.3 for PNI. After a median follow-up of 70 months, the 5-year overall survival (OS) and progression-free survival (PFS) were 56.2% and 49.5%, respectively. Patients in low PNI group had more unfavorable clinical features, and tended to have worse 5-year OS and PFS compared with those in high PNI group. According PNI-associated prognostic score, patients were classified into different risk groups. Significant difference has been found in 5-year OS and PFS in different risk groups. When PNI and PNI-associated prognostic score were superimposed on the International Prognostic Index (IPI), prognostic index of natural killer lymphoma (PINK), or nomogram-revised risk index (NRI) categories, the PNI and PNI-associated prognostic score provided additional prognostic information. Therefore, PNI and PNI-associated prognostic score could be independent prognostic factors for ENKTL and may be useful for risk stratification and clinical decision-making.

First-line LVDP (L-asparaginase, etoposide, dexamethasone, and cisplatin) regimen combined with radiotherapy is effective for early-stage extranodal natural killer/T-cell lymphoma, nasal type.

Chemotherapy combined with radiotherapy could reduce the risk of recurrence in early-stage extranodal NK/T lymphoma (ENKTL). However, the optimal combined chemotherapy regimen is still unknown. Our previous study reported that LVDP (L-asparaginase, etoposide, dexamethasone, and cisplatin) combined with radiotherapy was a potentially effective and safe treatment regimen for early-stage ENKTL. This study further validated the efficacy and safety of LVDP chemotherapy combined with radiation for early-stage ENKTL with more patients and longer follow-up. We retrospectively studied 112 patients with early-stage ENKTL from September 2010 to September 2019. All patients received the LVDP regimen, and 101 of them received radiotherapy. The patients' characteristics, treatment responses, survival outcomes, prognostic factors, and toxicities were analyzed. The median follow-up was 60 months (range, 4 to 117). All patients received median 4 cycles of the LVDP chemotherapy. At the end of therapy, the objective response rate and complete response rate were 88.3% and 77.6%, respectively. The 3- and 5-year OS were 79.6% and 73.2%, and the 3- and 5-year PFS were 75.4% and 71.6%, respectively. Among them, the LVDP regimen combined with radiotherapy yielded more favorable treatment outcomes (the 3-year OS and PFS were 83.1% and 80.8%). The most common severe hematologic toxicity was leukopenia (25% grade 3/4), and the most common severe non-hematologic toxicity was increased transaminase (4.5% grade 3/4). No pancreatitis or treatment-related death occurred. The LVDP regimen combined with radiotherapy had a good therapeutic response and long-term survival with tolerable toxicity for patients with early-stage ENKTL.