Risk Factors For Progression-free Survival Research Articles

TBI/Cy followed by auto-HSCT is a good choice next to allo-HSCT for patients with T-LBL/ALL

The aim of this retrospective study was to evaluate the efficiency and safety of total body irradiation plus cyclophosphamide (TBI/Cy) followed by autogenetic hematopoietic stem cell transplantation (auto-HSCT) in T-LBL/ALL patients that cannot receive allogeneic hematopoietic stem cell transplant (allo-HSCT). Between 2013 and 2023, 24 patients received auto-HSCT following by TBI/Cy, 26 patients underwent allo-HSCT, all patients achieved completed hematopoietic reconstitution after HSCT. The progression free survival (PFS) and overall survival (OS) had no statistically significant differences between the two groups (P = 0.791, HR 1.127, 95%CI 0.456–2.785; P = 0.456, HR 0.685, 95%CI 0.256–1.828). Although the cumulative incidence of relapse was lower for patients who received allo-HSCT than auto-HSCT (P = 0.033, HR 3.707, 95%CI 1.188–11.570, 2-year relapse 11.5% vs. 33.3%), the incidence of non-relapse mortality (NRM) was higher than that in the auto-HSCT group (P = 0.014, HR 0.000, 95%CI -1.000 - -1.000, 2-year NRM, 23.1% vs. 0%). Trough Landmark analysis, the two groups showed a statistically significant difference in 3-year PFS and 4-year OS curves (Figure S2A&B, P = 0.039, HR 0.426, 95%CI 0.163–1.117; P = 0.014, HR 0.317, 95%CI 0.113–0.887). By COX analysis, poor baseline performance status (ECOG-PS ≥ 2) and CNS involvement were risk factors for PFS and OS. In conclusion, TBI/Cy followed by auto-HSCT is a good choice next to allo-HSCT for patients with T-LBL/ALL.

Vasculogenic mimicry triggers early recidivation and resistance to adjuvant therapy in esophageal cancer

ObjectiveTo investigate the impact of vasculogenic mimicry (VM) and postoperative adjuvant therapy on the prognosis and survival of patients with esophageal squamous cell carcinoma (ESCC), as well as to assess whether VM affects the clinical benefit of postoperative adjuvant therapy.MethodsThis single-center retrospective analysis included patients who underwent radical surgery for ESCC, which was documented in the medical record system. The presence or absence of VM in surgical specimens was determined using double staining with PAS/CD31. Stratification was applied based on adjuvant therapy and VM status. Survival curves and COX modeling were used to analyze the impact of the presence or absence of VM on the benefit of adjuvant therapy and the survival prognosis of patients.ResultsVM-positive patients were more prone to postoperative recurrence and metastasis. VM was identified as an independent risk factor for progression-free survival (PFS) (p < 0.001, 95% CI:1.809–3.852) and overall survival (OS) (p < 0.001, 95% CI:1.603–2.786) in postoperative ESCC. Postoperative adjuvant therapy significantly prolonged PFS (p = 0.008) and OS time (p < 0.001) in patients with stage II and III ESCC, with concurrent chemoradiotherapy being the most effective. However, the presence of VM significantly reduced the benefits of postoperative adjuvant therapy (p < 0.001).ConclusionVM negatively impacts the prognosis of postoperative ESCC patients and reduces the efficacy of postoperative adjuvant therapy.

Analysis of the efficacy and safety of dual immunotherapy in patients with driver gene and programmed death ligand-1 double negative advanced non-small cell lung cancer

Objective: To discuss the efficacy and safety of the dual immunotherapy of nivolumab plus ipilimumab in patients with advanced non-small cell lung cancer (NSCLC) who are double negative for driver gene and programmed death-ligand 1 (PD-L1) expression. Methods: We conducted a retrospective collection of clinical data for 61 patients with advanced NSCLC who were negative for both driver genes and PD-L1 and received dual immunotherapy with nivolumab plus ipilimumab at the First Affiliated Hospital of Guangzhou Medical University from January 2019 to June 2023. Based on treatment conditions, patients were divided into first-line and non-first-line dual immunotherapy groups. Patients were followed up monthly, with the follow-up period ending on October 1, 2023. The efficacy was evaluated using Solid Tumor Response Evaluation Criteria, and adverse reactions were assessed according to the Common Terminology Criteria for Adverse Events developed by the National Cancer Institute in the United States. Survival curves were plotted using the Kaplan-Meier method, and the log-rank test was used to compare the differences in progression-free survival (PFS) and overall survival (OS) between first-line and non-first-line dual immunotherapy patients. The influence factors of PFS were analyzed using a multivariate Cox proportional hazards regression model. Results: Among the 61 NSCLC patients, 49 were male (80.3%), with an age range of 23-88 years [(65.3±7.4) years]. There were 14 cases (23.0%) classified as stage ⅢC and 47 cases (77.0%) classified as stage Ⅳ according to TNM staging. Forty cases (65.6%) received non-first-line treatment. The objective response rate (ORR) was 24.6% (15/61), and the disease control rate (DCR) was 52.5% (32/61). All 61 patients were followed up, with a median follow-up time of 17.8 months. The median PFS was 6.0 months (95%CI: 5.5-6.4 months), and the median OS was 17.0 months (95%CI: 14.8-19.2 months). For patients receiving first-line dual immunotherapy, the median PFS was longer than for those receiving non-first-line dual immunotherapy [7.0 months (95%CI: 6.0-7.9 months) vs 4.0 months (95%CI: 3.3-4.6 months), P<0.001]; similarly, the median OS for patients receiving first-line dual immunotherapy was longer than for those receiving non-first-line dual immunotherapy [19.0 months (95%CI: 18.1-19.9 months) vs 13.0 months (95%CI: 10.8-15.1 months), P<0.001]. Multivariate Cox risk regression model analysis showed that distant tumor metastasis (HR=1.414, 95%CI: 1.253-1.725), non-first-line dual immunotherapy (HR=1.412, 95%CI: 1.184-1.652), and tumor mutation burden<10 mut/Mb (HR=1.328, 95%CI: 1.151-1.546) were risk factors for PFS, while non-squamous carcinoma (HR=0.917, 95%CI: 0.823-0.984) was a protective factor for PFS. Immune-related adverse reactions occurred in 41 cases (67.2%), including 21 cases (32.8%) of grade 3-4 adverse reactions. Eight cases (13.1%) discontinued treatment, and there were no deaths. Conclusions: Dual immunotherapy with nivolumab plus ipilimumab can be a treatment option for driver gene and PD-L1 double-negative advanced NSCLC. Distant tumor metastasis, non-first-line dual immunotherapy, and tumor mutation burden<10 mut/Mb are risk factors affecting patients' PFS, while non-squamous cell carcinoma is a protective factor affecting patients' PFS.

Prognostic value of lactate dehydrogenase to absolute lymphocyte count ratio and albumin to fibrinogen ratio in diffuse large B-cell lymphoma.

With the continuous improvement of treatment strategy, the prognostic value of international prognostic index (IPI) alone is limited for diffuse large B-cell lymphoma (DLBCL). Our study aims to explore the effect of lactate dehydrogenase (LDH)to absolute lymphocyte count (ALC) ratio (LAR) and albumin to fibrinogen ratio (AFR) on the prognosis of patients with DLBCL. The venous blood LDH, ALC, albumin and fibrinogen within 1 week before the first chemotherapy in 74 DLBCL patients were collected to calculate the LAR and AFR values. The impact of LAR and AFR on the progression-free survival (PFS) of patients with DLBCL was studied by the survival analysis. The area under the receiver operating characteristic curve (AUC) and concordance index (C-index) were used to analyze the predictive efficiency of each model for the PFS of DLBCL patients. Cox univariate analysis suggested that elevated LAR (P < .001) and decreased AFR (P < .001) were risk factors for PFS in DLBCL patients. Multivariate analysis revealed that LAR (P < .001) and AFR (P = .004) were 2 independent prognostic parameters. The AUC values of IPI, AFR + IPI, LAR + IPI and AFR + LAR + IPI to predict the PFS of DLBCL patients were 0.806 (95%CI 0.707-0.905, P < .001), 0.839 (95%CI 0.747-0.932, P < .001), 0.851 (95%CI 0.764-0.938, P < .001), and 0.869 (95%CI 0.787-0.952, P < .001), respectively. The C-index values of above 4 models were 0.802 (95%CI 0.629-0.975, P < .001), 0.842 (95% CI 0.735-0.949, P < .001), 0.846 (95%CI 0.716-0.976, P < .001), and 0.864 (95%CI 0.781-0.941, P < .001), respectively. The results suggest that both LAR and AFR are independent prognostic factors for PFS in DLBCL patients. Furthermore, their combination with IPI has better predictive efficiency for the prognosis of DLBCL patients.

Prognostic Value of Ki67 in Epithelial Ovarian Cancer: Post-Neoadjuvant Chemotherapy Ki67 Combined with CA125 Predicting Recurrence.

To evaluate Ki67 expression and prognostic value during neoadjuvant chemotherapy (NACT) in advanced epithelial ovarian cancer (EOC). 95 patients with advanced EOC receiving NACT followed by interval debulking surgery (IDS) were available for tissue samples from matched pre- and post-therapy specimens. The expression of Ki-67 was evaluated by immunohistochemistry and classified by percentage of stained cells. The optimal cutoff values of the Ki67 were assessed by receiver operating characteristic analysis. Kaplan-Meier analysis, the Log rank test, and Cox regression analysis were carried out to analyze survival. Post-NACT Ki67 was an independent prognostic factor for recurrence by univariate (HR: 1.8, 95% CI: 1.1-3.0, P-value: 0.023) and multivariate (HR: 1.88, 95% CI: 1.08-3.26, P-value: 0.025) analysis. Residual disease >1cm (HR: 2.69, 95% CI: 1.31-5.54, P-value: 0.0070) and pre-treatment CA125 ≥ 1432 U/mL (HR: 2.00, 95% CI: 1.13-3.55, P-value: 0.017) were also independent risk factors for progression-free survival (PFS) in multivariate analysis. Post-NACT Ki67 ≥ 20% was an independent risk factor for PFS, however, baseline Ki67 and Ki67 change did not suggest prognostic significance. In patients with high CA125, the median PFS for patients with high postKi67 (median PFS: 15.0 months, 95% CI: 13.4-16.6 months) was significantly (P-value: 0.013) poorer compared to patients with low postKi67 (median PFS: 30.0 months, 95% CI: 13.5-46.5 months). Post-NACT Ki67 ≥ 20% was an independent factor associated with poorer PFS in patients with advanced-stage EOC undergoing NACT followed by IDS. The combination of post-NACT Ki67 and pretreatment CA125 could better identify patients with poorer PFS in NACT-administered patients.

Analysis of clinical and pathological characteristics of retroperitoneal paraganglioma and associated prognostic factors.

The aim of this study is to explore the long-term prognostic risk factors associated with patients diagnosed with retroperitoneal paraganglioma (RPGL) and examine their clinical and pathological characteristics. Expressions of biomarkers were identified using immunohistochemistry (IHC) and case databases were retrospectively searched. Survival analysis was performed using Kaplan-Meier and Cox risk regression to identify the factors that influence the postoperative progression-free survival of patients with RPGL. A total of 105 patients, most of whom had tumors situated in the paraaortic region, and whose average tumor size was 8.6 cm, were enrolled in this study. The average follow-up duration was 51 months, with a mortality rate of 19% and a recurrence and metastasis rate of 41.9%. Tumors were assessed using the modified Grading system for Adrenal Pheochromocytoma and Paraganglioma (GAPP), and SDHB, S-100, and Ki-67 were stained using IHC in all cases. Out of the total cases examined, negative in SDHB expression were observed in 18.1% of cases, S-100 expression was negative in 36.2% of cases, and endovascular tumor enboluswas present in approximately 25.7% of cases. The results of the univariate analysis indicated that several factors significantly influenced the progression-free survival of patients with PGL as follow: maximum tumor diameter (>5.5 cm), tumor morphological features, tumor grading (modified GAPP score > 6), SDHB negative, S-100 negative, and expression of proliferation index Ki-67 (>3%) (X2 = 4.217-27.420, p < 0.05). The results of the multivariate analysis indicated that negative of S-100 (p = 0.021) and SDHB (p = 0.038), as well as intravascular tumor thrombus (p = 0.047) expression were independent risk factors for progression-free survival in patients. RPGL is characterized by diverse biological features and an elevated susceptibility to both recurrence and metastasis. Both SDHB and S-100 can be employed as traditional IHC indicators to predict the metastatic risk of PGL, whereas the tumor histomorphology-endovascular tumor enbolus assists in determining the metastasis risk of RPGL.

Clinicopathological features, prognostic factor analysis, and survival nomogram of patients with double primary cancers involving lung cancer.

Although the incidence of double primary cancers (DPCs) involving lung cancer is rising, they have not been studied sufficiently. This study retrospectively analyzed the clinicopathological and prognostic characteristics of DPC patients with lung cancer and developed a survival nomogram to predict the individual OS rates. We included 103 DPC patients with lung cancer from Shengjing Hospital between 2016 and 2021. Based on the 6-month cancer occurrence interval, the cases were categorized as synchronous DPCs (sDPCs) or metachronous DPCs (mDPCs). Furthermore, the mDPCs were subdivided based on whether the lung cancer occurred first (LCF cohort) or the other cancer occurred first (OCF cohort). Among the patients, 35 (33.98%) and 68 (66.02%) had sDPCs and mDPCs, respectively. In the mDPCs cohort, 18 (26.47%) belonged to the LCF cohort and 50 (73.53%) to the OCF cohort. The most frequent primary cancer sites were the breast (27.18%), colorectum (22.33%), and urinary system (18.45%). Independent risk factors for progression-free survival were Stage IV lung cancer (p = 0.008) and failure to undergo radical lung cancer surgery (p = 0.028). The risk factors for OS included squamous carcinoma (p = 0.048), Stage IV lung cancer (p = 0.001), single cancer resection plus drug therapy (p < 0.001), drug therapy alone (p = 0.002), failure to undergo radical lung cancer surgery (p = 0.014), and chemotherapy (p = 0.042). The median OS was 37 months, with 3- and 5-year rates of 50.9% and 35.9%, respectively. DPCs involving lung cancer account for 1.11% of cases. The breast, colorectum, and urinary system were the most common extra-pulmonary sites, and mDPCs were more frequent than sDPCs. Radical lung cancer surgery significantly affects prognosis, and drug therapy alone may be preferable when only one tumor is operable. The developed nomogram can accurately predict individual 3-year and 5-year OS rates.

Potential Value of HSP90α in Prognosis of Triple-Negative Breast Cancer.

BACKGROUND Triple-negative breast cancer (TNBC) is a distinct subtype of breast cancer, accounting for 12-18% of all breast cancer cases. It exhibits high heterogeneity and aggressiveness, resulting in a poorer prognosis with a high risk of early recurrence and metastasis. Due to the lack of expression of estrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptor 2 (HER2), as well as insensitivity to endocrine therapy, determining a standard treatment for TNBC is challenging. The identification of potential prognostic biomarkers is crucial for developing personalized treatment strategies for patients. MATERIAL AND METHODS Our study investigated the potential value of HSP90a in TNBC prognosis. A retrospective analysis was conducted on 127 TNBC patients and 127 Healthy controls from March 1, 2019 to July 31, 2022. Venous blood was collected and tested for HSP90alpha, CEA, CA199, and CA125, and we recorded the clinical characteristics of the patients, including age, BMI, alcohol consumption status, surgical history, CEA level, CA199 level, CA125 level, HSP90alpha level, tumor size, distant metastases, lymph node metastasis, and TNM stage. Univariate and multivariate methods were used to screen independent risk factors for progression-free survival (PFS) and overall survival (OS). RESULTS HSP90alpha is not only upregulated in TNBC but is also highly correlated with lymph node metastasis and TNM stage. The results of multivariate analysis showed that distant metastasis, TNM stage and HSP90a level were independent factors associated with PFS. BMI, tumor size, TNM stage, surgical history, and HSP90a level were independent factors influencing OS. CONCLUSIONS Our research findings demonstrate a significant association between high HSP90alpha expression and adverse clinical features, suggesting a poorer prognosis for TNBC patients.

Effects of Pre-Transplant CONUT and Post-Transplant MRD on Prognosis of Patients with Multiple Myeloma after Auto-HSCT

To explore the effects of pre-transplant controlling nutritional status (CONUT) and post-transplant minimal residual disease (MRD) on prognosis of patients with multiple myeloma (MM) after autologous hematopoietic stem cell transplantation (auto-HSCT). The clinical data of 79 patients who received auto-HSCT from 2011 to 2020 in The First Affiliated Hospital of Chongqing Medical University were retrospectively analyzed. The patients were divided into Low-CONUT group (n=62) and High-CONUT group (n=17) according to whether the CONUT score was less than 5. The differences in clinical features, hematopoietic reconstruction, adverse reactions, efficacy and survival between the two groups were compared. In addition, the prognostic risk factors were analyzed and verified by time-dependent ROC curve. The proportions of male patients and bone marrow plasma cells>30% at initial diagnosis in High-CONUT group were both higher than those in Low-CONUT group (both P <0.05). While, there were no significant differences in hematopoietic reconstruction and adverse reactions (>grade 2) between the two groups. The complete response (CR) rate and CR+very good partial response (VGPR) rate before transplantation in Low-CONUT group were both significantly higher than those in High-CONUT group (both P <0.05). After 3 months of transplantation, the CR+VGPR rate still remained an advantage in Low-CONUT group compared with High-CONUT group (P <0.01), but CR rate did not(P >0.05). The overall survival (OS) and progression-free survival (PFS) in Low-CONUT group were both superior to those in High-CONUT group (both P <0.05). Low CONUT score (0-4) before transplantation and negative MRD at 6 months after transplantation were favorable factors affecting OS and PFS (both P <0.05), while the International Myeloma Working Group (IMWG) high-risk at initial diagnosis and lactate dehydrogenase (LDH) level>250 U/L before transplantation were only risk factors for PFS (both P <0.05). Time-dependent ROC curve analysis showed that pre-transplant CONUT score and MRD status at 6 months after transplantation could independently or jointly predict 1- and 2-year OS and PFS, and the combined prediction was more effective. The combination of pre-transplant CONUT and post-transplant MRD can better predict the prognosis of MM patients.

Effectiveness and safety of vascular intervention plus lenvatinib versus vascular intervention alone for hepatocellular carcinoma patients with portal vein tumor thrombus: a retrospective comparative study.

This study aimed to assess the effectiveness and safety of vascular intervention combined with lenvatinib versus vascular intervention alone in the treatment of advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT), and to identify prognostic factors associated with the treatment outcomes. We conducted a retrospective analysis of data from 92 patients with advanced HCC and PVTT who were treated between February 2016 and February 2023. Among them, 56 patients underwent vascular intervention alone (transarterial chemoembolization, TACE), while 36 patients received vascular intervention (TACE or hepatic arterial infusion chemotherapy [HAIC]) combined with lenvatinib. The primary outcomes included progression-free survival (PFS), overall survival (OS), and objective response rate (ORR). Survival rates were estimated by the Kaplan-Meier method, and confounders were adjusted using inverse probability of treatment weighting (IPTW). Prognostic factors were determined through the Cox regression model. The median follow-up duration was 20.07 months (interquartile range: 6.41-25.36). The combination therapy group had a significantly longer median PFS (11.00 vs. 5.00 months, P<0.05) and OS (12.91 vs. 6.83 months, P<0.05) in comparison to the monotherapy group, and these findings remained consistent after IPTW matching. Moreover, the combination therapy group showed a higher ORR (55.56% vs. 26.79%, P<0.05) based on mRECIST criteria. Cox multivariate analysis identified extrahepatic metastasis and maximum tumor diameter as risk factors for PFS, while age, tumor number, and maximum tumor diameter influenced OS. Combined treatment emerged as a protective factor for OS. In the combination therapy group, hypertension was the most frequent adverse event, with grade 3 or 4 adverse events occurring rarely. The combination of vascular intervention with lenvatinib has demonstrated improved PFS and OS in advanced HCC patients with PVTT, and its safety profile appears to be acceptable. Adoption of this combined treatment strategy at an earlier stage may enhance patient outcomes.

Clinical Features and Prognosis Analysis of 168 Cases of MYC/BCL2 Double Expression Diffuse Large B Lymphoma

Objective: A retrospective study of the clinical features and prognosis of MYC/BCL2 double-expressor diffuse large B-cell lymphoma (DEL). Methods: A retrospective analysis was conducted on patients diagnosed with MYC/BCL2 double-expressor diffuse large B-cell lymphoma (DEL) for the first time by pathological and fluorescence in situ hybridization (FISH) techniques at Fujian Medical University Affiliated Union Hospital from January 2017 to December 2021. Clinical features, immunohistochemistry, laboratory tests, treatment plans, and follow-up information of all patients were collected. Kaplan-Meier analysis was used for univariate analysis, and Cox proportional hazards model was used for multivariate analysis. Results: Clinical characteristics:Among the 168 patients with diffuse large B-cell lymphoma (DLBCL), 13 cases (7.7%) involved the primary central nervous system. Of the patients, 95 (56.55%) were male and 73 (43.45%) were female, resulting in a male-to-female ratio of 1.3:1. The age of onset was at least 60 years for 93 cases (55.36%), with the youngest being 22 years old and the oldest being 88 years old. The median age was 62 years old. A total of 113 cases (72.90%) were classified as stage III-IV by the Ann Arbor staging system, 40 cases (23.81%) had B symptoms, 82 cases (52.90%) had an International Prognostic Index (IPI) score of 3-4, 84 cases (54.19%) had involvement of two or more extranodal sites, 87 cases (51.79%) had a β2-microglobulin (β2-MG) level of ≥2.53mg/L, 122 cases (72.62%) had a serum albumin (SA) level of &amp;lt;35g/L, and 103 cases (61.31%) had elevated levels of lactate dehydrogenase (LDH).Survival status: Complete follow-up data were available for 162 DEL patients, with a median follow-up time of 20.38 (1-73) months. The median overall survival (OS) was not reached, while the median progression-free survival (PFS) was 37.1 months. Among them, and 58 (34.5%) died. Survival analysis was performed on 168 DEL patients, with 1-year, 3-year, and 5-year OS rates of 82.1%, 61.1%, and 58.9%, respectively. The 1-year, 3-year, and 5-year PFS rates were 69.5%, 51.4%, and 45.6%, respectively. Among the 93 elderly (≥60 years old) DEL patients, the 1-year, 3-year, and 5-year OS rates were 77.2%, 52.7%, and 48.6%, respectively, and the 1-year, 3-year, and 5-year PFS rates were 67.4%, 47.4%, and 43.7%, respectively. The 1-year and 3-year OS rates of the 13 patients with primary central nervous system DLBCL were 25.50%, and the 1-year and 3-year PFS rates were 16.70%.Clinical efficacy analysis: Among 168 patients with DEL, the complete remission (CR) rate was 62.5% (105/168), the partial remission (PR) rate was 3.5% (6/168), the overall effective rate (ORR) was 66.1%, and the relapse/progression rate was 25.6% (43/168). Comparing the efficacy of 88 patients treated with the R-CHOP regimen with 32 patients treated with sildalafil combined with the R-CHOP regimen, the results showed a higher CR rate (81.25% vs. 67.05%) and a lower relapse rate (3.13% vs. 12.5%) in patients treated with sildalafil combined with the R-CHOP regimen.4. Univariate analysis: Age over 60 years ( P=0.031), B symptoms ( P=0.031), advanced Ann Arbor stage (P=0.003), high IPI score ( P&amp;lt;0.001), elevated LDH ( P=0.031), and elevated β2-MG( P&amp;lt;0.001) were significantly correlated with poor prognosis in DEL patients, and were identified as adverse prognostic factors. Non-GCB subtype ( P=0.029), B symptoms ( P&amp;lt;0.001), advanced Ann Arbor stage ( P&amp;lt;0.001), high IPI score ( P&amp;lt;0.001), decreased serum albumin ( P&amp;lt;0.001), elevated LDH (P=0.085), and elevated β2-MG(P&amp;lt;0.001) were significantly associated with poorer progression-free survival (PFS) among DEL patients.5.Multivariate analysis revealed that elevated β2-MG levels and high IPI scores were independent risk factors for poor overall survival (OS) in DEL patients, with HR values of 2.363 and 7.090, respectively. B symptoms, elevated β2-MG levels, and reduced serum albumin (SA) levels were independent risk factors for poor progression-free survival (PFS) in DEL patients, with HR values of 1.819, 2.879, and 1.987, respectively. Conclusion: Elevated β2-microglobulin and high IPI scores in DEL patients are risk factors for OS, while B symptoms, elevated β2-microglobulin, and decreased serum albumin are risk factors for PFS. Keywords: Lymphoma, diffuse large B-cell, clinical features, prognosis, double- expression lymphoma

The Prognostic Impact of Relative Dose Intensity of Vincristine in R-CHOP for Untreated Patients with Diffuse Large B-Cell Lymphoma: A Supplementary Analysis of JCOG0601

Introduction R-CHOP (rituximab, cyclophosphamide [CY], doxorubicin [DXR], vincristine [VCR], and prednisolone) is the standard of care for diffuse large B-cell lymphoma (DLBCL) and cures around 60% of patients. However, some DLBCL survivors suffer from long-lasting peripheral neuropathy (PN) caused by VCR, and the dose of VCR is usually decreased to prevent severe PN. Though, there is a lack of information regarding the effect of VCR dose reduction on DLBCL prognosis, especially based on data from prospective clinical trials. Recently, VCR dose reduction was not associated with poor prognosis in patients with aggressive B-cell lymphomas, based on the results of the RICOVER-60 trial (NCT00052936) (Bewarder et al., Haematologica 2023). In this trial, R-CHOP was administered in 14-day cycles. To evaluate the clinical impact of relative dose intensity (RDI) of VCR (RDI O) in patients with DLBCL treated with tri-weekly R-CHOP (R-CHOP21), we conducted a supplemental analysis of the JCOG0601: randomized phase II/III trial of the Japan Clinical Oncology Group (jRCTs031180139). In the JCOG0601 trial, RW-CHOP21 (CHOP21 with eight doses of weekly rituximab) and R-CHOP21 were compared for progression-free survival (PFS) (Ohmachi et al., Blood Adv. 2021). Methods Between 2007 and 2014, 422 patients were enrolled in the JCOG0601 trial. Among them, 401 patients who received at least six courses of R-CHOP21 (n=206) or RW-CHOP21 (n=195) were eligible for this supplemental analysis. Those who could not complete six courses of chemotherapy were excluded because their treatment outcomes might be impaired mainly due to their disease aggressiveness and not the dose intensity of chemotherapy. As PFS was not significantly different between the two treatment arms, these 401 patients were analyzed together (Figure A). The impact of decreased RDI O on PFS was assessed using the Cox proportional hazard model and two-sided log-rank p-values with several cutoff values of RDI O (95, 90, 85, 80, 70, 60, or 50%). The VCR dose was reduced according to the protocol. As a subgroup analysis, the impact of RDI O was evaluated in patients whose RDI of CY and DXR (RDI C+H) were retained, defined as RDI C+H were both ≥85% (high RDI C+H), or not retained, defined as either or both of RDI C+H were &amp;lt;85% (low RDI C+H). Clinical factors, including the cell of origin (COO), as defined by the Hans algorithm, were evaluated for their association with poor PFS. Result The baseline clinical characteristics of the 401 patients were as follows: median age, 62 years (range, 20-79), male sex (54.6%); performance status of 0 or 1 (97.5%); Ann Arbor stage Ⅰ or Ⅱ (53.4%); and International Prognostic Index (IPI) of low or low-intermediate (82.6%). The median RDI O of the 401 patients was 97% (interquartile range [IQR], 89-100). The median RDI of CY and DXR were as high (96% each). At the data cut-off date (Dec 2017), the median follow-up time was 59.4 months, and the 3-year PFS was 81.5% (95% confidence interval [CI], 77.3-85.0). Among the cutoff values investigated, 95% of RDI O (&amp;lt;95% [n=161], ≥95% [n=240]) showed the smallest p value (log-rank test, p = 0.0679), and the hazard ratio (HR) of low RDI O against high RDI O was 1.452 (95% CI, 0.971-2.171) (Figure B); RDI O &amp;lt;95% clinically means VCR dose was reduced in one or more times. A cutoff value of 95% was used for further analyses. Patients with RDI O &amp;lt;95% tended to have low RDI C+H. According to RDI O of &amp;lt;95% vs. ≥95%, there was a similar difference in the subgroup of patients with high RDI C+H as in the whole population (n=324, HR 1.508, 95% CI 0.934-2.434), but no remarkable difference in low RDI C+H (n=77, HR 0.932, 95% CI 0.432-2.009). Multivariable analysis revealed that the presence of B symptoms (HR 1.859, 95% CI 1.078-3.207) and high-intermediate or high IPI scores (HR 1.721, 95% CI 1.031-2.873) were risk factors for PFS. However, neither RDI O &amp;lt;95%, low RDI C+H, nor COO subtypes showed no remarkable impact on poor PFS in this patient population. Conclusion Our study demonstrated that among patients with DLBCL who completed six or more courses of R-CHOP21, VCR dose reduction was not associated with poor PFS as much as the presence of B symptoms and high IPI risk. VCR dose reduction driven by toxicity might not impair its efficacy if patients can complete R-CHOP21 therapy.

Epigenetic alterations in urothelial bladder cancer associated with disease outcomes.

Bladder cancer (BLCA) is a molecular heterogeneous disease with known genetic distinctive signatures. However, DNA methylation is highly prevalent across a wide range of tumors, suggesting its potential in oncogenesis. Here, we aimed to interrogate the role of nine epigenetic alterations as diagnostic and prognostic markers in BLCA. DNA methylation, gene expression, and clinicopathological information were retrieved from The Cancer Genome Atlas data portal. Methylation values and gene expression were assessed to determine their association with normal and malignant tissue. Additionally, we studied the association between methylation values and clinicopathological variables. For the prognostic model, Kaplan-Meier Survival curves were generated. Lastly, univariate and multivariate analysis were performed to evaluate the simultaneous impact of methylation and clinicopathological variables on the risk of tumor progression and survival. Nine CpG sites' methylation -values involved in our study demonstrated different methylation signatures between normal and malignant urothelium. Hypermethylated CpGs were overrepresented in tumor tissue (p < 0.0001). Opposingly, 4 CpG sites showed lower methylation values in tumor samples (p < 0.0001). Cg12743248high and cg17192862low are risk factors for progression-free survival, whereas cg12374721high (HR:3.003 (1.283-7.030)) also demonstrated to be the most valuable independent risk factor for disease progression and a risk factor for overall survival. We have identified that methylated cg12374721 shows promise as a diagnostic and independent prognostic marker in BLCA progression.

25-Hydroxy vitamin D deficiency is an inferior predictor of peripheral T-cell lymphomas.

The aim of the study was to explore the significance and prognostic value of 25-hydroxy vitamin D (25-(OH) D) deficiency in peripheral T-cell lymphomas (PTCLs). One hundred fifty-six patients of newly diagnosed PTCLs were enrolled in the study. Univariate and multivariate regression analyses were performed to determine independent risk factors for progression-free survival (PFS) and overall survival (OS). Receiver operating characteristic (ROC) curves were plotted, and corresponding areas under the curve (AUC) were calculated to estimate the accuracy of International Prognostic Index (IPI) plus 25-(OH) D deficiency and Prognostic Index for T-cell lymphoma (PIT) plus 25-(OH) D deficiency respectively in PTCL risk stratification. Our results showed that the 25-(OH) D deficiency was an independent inferior prognostic factor for both PFS (P = 0.0019) and OS (P = 0.005) for PTCLs, especially for AITL and PTCL-not otherwise specified (PTCL-NOS). Additionally, adding 25-(OH) D deficiency to PIT indeed has a superior prognostic significance than PIT alone for PFS (P = 0.043) and OS (P = 0.036). Multivariate COX regression analysis revealed that PIT 2‒4, albumin (ALB) ≤ 35g/L, and 25-(OH) D deficiency were regarded as independent risk factors of PFS and OS. Our results showed that 25-(OH) D deficiency was associated with inferior survival outcome of PTCLs, especially for AITL and PTCL-NOS. PIT plus 25-(OH) D deficiency could better indicate the prognosis for PFS and OS of PTCLs than PIT.

Primary adult choroid plexus carcinomas: a single-center experience with a systematic review.

Primary adult choroid plexus carcinomas (PACPCs) are extremely rare brain tumors. The existing literature primarily comprises case reports, which limits our understanding of this uncommon disease. This study aims to describe the clinical characteristics and prognosis of PACPCs, as well as to identify optimal treatment strategies. We conducted a comprehensive analysis of clinical data from 7 patients with PACPCs who underwent surgical treatment at the Department of Neurosurgery, Beijing Tiantan Hospital, between March 2011 and March 2023. Additionally, a thorough search of the PubMed database was performed using the keywords "choroid plexus carcinoma" or "choroid plexus carcinomas" within the time frame of August 1975 to April 2023, which yielded a total of 28 identified cases. Subsequently, we evaluated risk factors for progression-free survival (PFS) and overall survival (OS) based on the pooled cases. The pooled cohort, consisting of 7 cases from our institution and 28 cases from the literature, included 20 males and 15 females with a mean age of 44.3 ± 14.7 years (range: 21-73 years). Gross-total resection (GTR) and non-GTR were achieved in 22 (62.9%) and 13 (37.1%) patients, respectively. Radiotherapy and chemotherapy were administered to 29 (90.6%) and 13 (40.6%) patients, respectively. After a mean follow-up of 21.0 ± 26.7 months (range: 2-132 months), 18 patients were alive, and 11 patients had died. The multivariate Cox regression model demonstrated that non-GTR (HR 5.262, 95% CI 1.350-20.516, p=0.017) was a negative prognostic factor for OS. However, we did not find any risk factors for PFS. Complete surgical resection should be considered as the primary treatment approach for this rare disease. Chemotherapy and radiotherapy appear to have limited effectiveness in treating this condition. Further research with large cohorts is needed to validate our conclusions.

The baseline metabolism parameters of 18F‑FDG PET/CT as promising prognostic biomarkers in pediatric Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) is a rare myeloid precursor cell inflammatory neoplasia, which agonizes, maims, and even kills patients. Although clinical outcomes have steadily improved over the past decades, the progression/relapse rate of LCH remains high. The purpose of this study was to evaluate the prognostic value of the pre-treatment metabolism parameters of baseline 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F‑FDG PET/CT) in children with LCH. This cross-sectional study retrospectively and consecutively included 37 children (24 males and 13 females; median age, 5.1 years; range, 2.4-7.8 years) with pre-treatment 18F-FDG PET/CT from September 2020 to September 2022 in Nuclear Medicine Department, Beijing friendship hospital, Capital Medical University, Beijing, China. These patients were then all admitted to the hospital and diagnosed with LCH by biopsy, in Hematology Center, Beijing Children's Hospital, Capital Medical University, Beijing, China. Five metabolism parameters of 18F-FDG PET/CT were analyzed, including maximum standardized uptake, tumor-to-normal liver standard uptake value ratio, tumor-to-normal bone marrow standard uptake value ratio, sum of metabolic tumor volume (sMTV), and sum of total lesion glycolysis (sTLG) of all lesions. Patients were followed up for at least 1 year or until disease progression/relapse. Univariate and multivariate analyses of progression-free survival was performed. During follow-up, 11 (29.7%) patients had disease progression/relapse. Univariate analysis revealed that the risk organ involvement, the treatment response at the 5th or 11th week, pre-treatment sMTV, and sTLG were significantly associated with progression-free survival (P=0.024, 0.018, 0.006, 0.006, and 0.042, respectively). Multivariate COX analysis revealed that non-response at the 11th week, pre-treatment sMTV >32.55 g/cm3, and sTLG >98.86 g (P=0.002, 0.020, 0.026, respectively) were risk factors for progression-free survival. The baseline metabolism parameters of 18F-FDG PET/CT could be promising imaging biomarkers for predicting prognosis in children with LCH.

Clinical significance of genetic profiling based on different anatomic sites in patients with mucosal melanoma who received or did not receive immune checkpoint inhibitors

BackgroundTo date, data on the efficacy of targeted therapies for mucosal melanoma (MM) are limited. In this study, we analyzed genetic alterations according to the primary site of origin, which could provide clues for targeted therapy for MM.MethodsWe conducted a retrospective cohort study of 112 patients with MM. Targeted sequencing was performed to analyze genetic aberrations. Kaplan–Meier analysis was conducted with the log-rank test to compare the significance among subgroups.ResultsIn total, 112 patients with MM were included according to the anatomic sites: 38 (33.9%) in the head and neck, 22 (19.6%) in the genitourinary tract, 21 (18.8%) in the anorectum, 19 (17.0%) in the esophagus, 10 (8.9%) in the uvea, and 2 (1.8%) in the small bowel. The most significantly mutated genes included BRAF (17%), KIT (15%), RAS (15%), TP53 (13%), NF1 (12%), SF3B1 (11%), GNA11 (7%), GNAQ (5%), and FBXW7 (4%). A large number of chromosomal structural variants was found. The anatomic sites of esophagus and small bowel were independent risk factors for progression-free survival (PFS, hazard ratio [HR] 4.78, 95% confidence interval [CI] 2.42–9.45, P < 0.0001) and overall survival (OS, HR 5.26, 95% CI 2.51–11.03, P < 0.0001). Casitas B-lineage lymphoma (CBL) mutants showed significantly poorer PFS and OS. In contrast, MM patients who received immune checkpoint inhibitors (ICIs) had a significantly more favorable OS (HR 0.39, 95% CI 0.20–0.75, P = 0.008).ConclusionsOur findings reveal the genetic features of patients with MM, mainly across six anatomic sites, offering a potential avenue for targeted therapies.

Real-world efficacy and safety of cabozantinib following immune checkpoint inhibitor failure in Japanese patients with advanced renal cell carcinoma.

Real-world data of cabozantinib after failure of immune checkpoint inhibitors for advanced renal cell carcinoma in Japanese population are limited. Additionally, prognostic factors of cabozantinib in this setting are still unknown. We retrospectively evaluated data of 56 patients treated with cabozantinib subsequent to failed immune checkpoint inhibitors at four institutions. Regarding the efficacy profile, progression-free survival, overall survival and objective response rate were assessed. In terms of the safety profile, rate of adverse events, dose reduction and treatment interruption were assessed. Furthermore, risk factors of progression-free survival were analyzed. Twenty-nine patients (52%) were treated with cabozantinib as second-line therapy. Most frequent prior immune checkpoint inhibitor treatment was nivolumab plus ipilimumab combination therapy as first-line therapy (n=30, 54%). Median progression-free survival and overall survival were 9.76 and 25.5months, respectively, and objective response rate was 34%. All patients experienced at least one adverse event, and grade≥3 adverse events were observed in 31 patients (55%). Forty-four (79%) and 31 (55%) patients needed dose reduction and treatment interruption, respectively. Multivariate analysis showed that reduced initial dose (i.e. <60mg) (hazard ratio: 2.50, P=0.0355) and presence of lymph node metastasis (hazard ratio: 2.50, P=0.0172) were independent factors of shorter progression-free survival. Cabozantinib in Japanese patients with advanced renal cell carcinoma who failed immune checkpoint inhibitors was efficacious and had a manageable safety profile. These results appear to be similar to those of previous clinical trials.

Noninvasive evaluation of neutrophil extracellular traps signature predicts clinical outcomes and immunotherapy response in hepatocellular carcinoma.

Neutrophil extracellular traps (NETs) have been shown to play a pivotal role in promoting metastasis and immune escape in hepatocellular carcinoma (HCC). Therefore, noninvasive tests to detect the formation of NETs in tumors can have significant implications for the treatment and prognoses of patients. Here, we sought to develop and validate a computed tomography (CT)-based radiomics model to predict the gene expression profiles that regulate the formation of NETs in HCC. This study included 1133 HCC patients from five retrospective cohorts. Based on the mRNA expression levels of 69 biomarkers correlated with NET formation, a 6-gene score (NETs score, NETS) was constructed in cohort 1 from TCIA database (n=52) and validated in cohort 2 (n=232) from ICGC database and cohort 3 (n=365) from TCGA database. And then based on the radiomics features of CT images, a radiomics signature (RNETS) was developed in cohort 1 to predict NETS status (high- or low-NETS). We further employed two cohorts from Nanfang Hospital (Guangzhou, China) to evaluate the predictive power of RNETS in predicting prognosis in cohort 4 (n=347) and the responses to PD-1 inhibitor of HCC patients in cohort 5 (n=137). For NETS, in cohort 1, the area under the curve (AUC) values predicting 1, 2, and 3-year overall survival (OS) were 0.836, 0.879, and 0.902, respectively. The low-NETS was associated with better survival and higher levels of immune cell infiltration. The RNETS yielded an AUC value of 0.853 in distinguishing between high-NETS or low-NETS and patients with low-RNETS were associated with significantly longer survival time in cohort 1 (P<0.001). Notably, the RNETS was competent in predicting disease-free survival (DFS) and OS in cohort 4 (P<0.001). In cohort 5, the RNETS was found to be an independent risk factor for progression-free survival (PFS) (P<0.001). In addition, the objective response rate of HCC patients treated with PD-1 inhibitor was significantly higher in the low-RNETS group (27.8%) than in the high-RNETS group (10.8%). This study revealed that RNETS as a radiomics biomarker could effectively predict prognosis and immunotherapy response in HCC patients.

Prognostic factors in patients with thymoma who underwent surgery

PurposeThymoma is the most common primary tumor in the anterior mediastinum. The prognostic factors of patients with thymoma still need to be clarified. In this study, we aimed to investigate the prognostic factors of patients with thymoma who received radical resection and establish the nomogram to predict the prognosis of these patients.Materials and methodsPatients who underwent radical resection for thymoma with complete follow-up data between 2005 and 2021 were enrolled. Their clinicopathological characteristics and treatment methods were retrospectively analyzed. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method and compared by the log-rank test. Univariate and multivariate Cox proportional hazards regression analyses were performed to identify the independent prognostic factors. According to the results of the univariate analysis in the Cox regression model, the predictive nomograms were created.ResultsA total of 137 patients with thymoma were enrolled. With a median follow-up of 52 months, the 5-year and 10-year PFS rates were 79.5% and 68.1%, respectively. The 5-year and 10-year OS rates were 88.4% and 73.1%, respectively. Smoking status (P = 0.022) and tumor size (P = 0.039) were identified as independent prognostic factors for PFS. Multivariate analysis showed that a high level of neutrophils (P = 0.040) was independently associated with OS. The nomogram showed that the World Health Organization (WHO) histological classification contributed more to the risk of recurrence than other factors. Neutrophil count was the most important predictor of OS in patients with thymoma.ConclusionSmoking status and tumor size are risk factors for PFS in patients with thymoma. A high level of neutrophils is an independent prognostic factor for OS. The nomograms developed in this study accurately predict PFS and OS rates at 5 and 10 years in patients with thymoma based on individual characteristics.