Independent Factor For Progression-free Survival Research Articles

Survival Impact of Inflammation-based Prognostic Scores in Metastatic or Unresectable Esophageal Cancer Treated With Pembrolizumab Plus Chemotherapy.

Pembrolizumab plus chemotherapy has been indicated as the first-line treatment for metastatic or unresectable locally advanced esophageal cancer. However, pretreatment biomarkers for predicting clinical outcomes remain unclear. We investigated the predictive value of inflammation-based prognostic scores in patients treated with pembrolizumab and chemotherapy. The Prognostic Nutritional Index (PNI), C-reactive protein/albumin ratio (CAR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) were calculated before initial treatment in 65 eligible patients with metastatic or unresectable locally advanced esophageal cancer receiving pembrolizumab plus CF therapy, and the relationship between these biomarkers and clinical outcomes was analyzed. The objective response rate (ORR) and progression disease (PD) were observed in 51% and 21% of all patients. Patients with PNI<39 have significantly worse treatment responses than those with PNI≥39 (ORR; 28% vs. 60%, PD; 44% vs. 13%, P=0.020). Progression-free survival (PFS) is significantly associated with the PNI and CAR (P<0.001 and P=0.004, respectively). Overall survival (OS) is associated with PNI, CAR, and PLR (P<0.001, P=0.008, and P=0.018, respectively). The PNI cutoff value of 39 is identified as an independent factor for PFS (odds ratio=0.27, 95% CI: 0.18-0.81, P=0.012) and OS (odds ratio=0.22, 95% CI: 0.08-0.59, P=0.003). Patients with PNI<39 have significantly worse 6-month PFS and 1-year OS than those with PNI≥39 (27.8% vs. 66.7%, 27.2% vs. 81.1%, respectively). In conclusion, inflammation-based prognostic scores are associated with survival in patients treated with pembrolizumab plus CF therapy. Pretreatment PNI is a promising candidate for predicting treatment response and survival.

Aprospective study of detection and clinical significance of bone marrow tumor cells in small cell lung cancer

Objective: To investigate the detection of bone marrow tumor cells in small cell lung cancer (SCLC) patients and their relationship with clinical features, treatment response and prognosis. Methods: A total of 113patients with newly diagnosed SCLC from January 2018 to October 2022 at Beijing Chest Hospital were prospectively enrolled. Before treatment, bone marrow was aspirated and separately submitted for tumor cells detection by liquid-based cytology and disseminated tumor cells (DTCs) detection by the substrction enrichment and immunostaining fluorescence in situ hybridization (SE-iFISH) platform. The correlation between the detection results of the two methods with patients' clinical features and treatment response was evaluated by Chi-square. Kaplan-Meier method was applied to create survival curves and the Cox regression model was used for multivariate analysis. Results: The positive rate of bone marrow liquid-based cytology in SCLC was 15.93% (18/113). The liver and bone metastases rates were significantly higher (55.56% vs 11.58% for liver metastasis, P＜0.001; 77.78% vs 16.84% for bone metastasis, P＜0.001) and thrombocytopenia was more common (16.67% vs 2.11%, P=0.033) in patients with tumor cells detected in liquid-based cytology than those without detected tumor cells. As for SE-iFISH, DTCs were detected in 92.92% of patients (105/113), the liver and bone metastasis rates were significantly higher (37.93% vs 11.90% for liver metastasis, P=0.002; 44.83% vs 20.23 % for bone metastasis, P=0.010), and the incidence of thrombocytopenia was significantly increased (13.79% vs 1.19%, P=0.020) in patients with DTCs≥111 per 3 ml than those with DTCs＜111 per 3 ml. The positive rates of bone marrow liquid-based cytology in the disease control group and the disease progression group were 12.00% (12/100) and 46.15% (6/13), respectively, and the difference was statistically significant (P=0.002). However, the result of SE-iFISH revealed the DTCs quantities of the above two groups were 29 (8,110) and 64 (15,257) per 3 ml, and there was no statistical difference between the two groups (P=0.329). Univariate analysis depicted that the median progression-free survival (PFS) and median overall survival (OS) of liquid-based cytology positive patients were significantly shorter than those of tumor cell negative patients (6.33 months vs 9.27 months for PFS, P=0.019; 8.03 months vs 19.50 months for OS, P=0.019, P=0.033). The median PFS and median OS in patients with DTCs≥111 per 3 ml decreased significantly than those with DTCs＜111 per 3 ml (6.83 months vs 9.50 months for PFS, P=0.004; 11.2 months vs 20.60 months for OS, P=0.019). Multivariate analysis showed that disease stage (HR=2.806, 95%CI:1.499-5.251, P=0.001) and DTCs quantity detected by SE-iFISH (HR=1.841, 95%CI:1.095-3.095, P=0.021) were independent factors of PFS, while disease stage was the independent factor of OS (HR=2.538, 95%CI:1.169-5.512, P=0.019). Conclusions: Both bone marrow liquid-based cytology and SE-iFISH are clinically feasible. The positive detection of liquid-based cytology or DTCs≥111 per 3 ml was correlated with distant metastasis, and DTCs≥111 per 3 ml was an independent prognostic factor of decreased PFS in SCLC.

Prognostic analysis of related factors of adverse reactions to immunotherapy in advanced gastric cancer and establishment of a nomogram model.

Immunotherapy for advanced gastric cancer has attracted widespread attention in recent years. However, the adverse reactions of immunotherapy and its relationship with patient prognosis still need further study. In order to determine the association between adverse reaction factors and prognosis, the aim of this study was to conduct a systematic prognostic analysis. By comprehensively evaluating the clinical data of patients with advanced gastric cancer treated by immunotherapy, a nomogram model will be established to predict the survival status of patients more accurately. To explore the characteristics and predictors of immune-related adverse reactions (irAEs) in advanced gastric cancer patients receiving immunotherapy with programmed death protein-1 (PD-1) inhibitors and to analyze the correlation between irAEs and patient prognosis. A total of 140 patients with advanced gastric cancer who were treated with PD-1 inhibitors in our hospital from June 2021 to October 2023 were selected. Patients were divided into the irAEs group and the non-irAEs group according to whether or not irAEs occurred. Clinical features, manifestations, and prognosis of irAEs in the two groups were collected and analyzed. A multivariate logistic regression model was used to analyze the related factors affecting the occurrence of irAEs, and the prediction model of irAEs was established. The receiver operating characteristic (ROC) curve was used to evaluate the ability of different indicators to predict irAEs. A Kaplan-Meier survival curve was used to analyze the correlation between irAEs and prognosis. The Cox proportional risk model was used to analyze the related factors affecting the prognosis of patients. A total of 132 patients were followed up, of whom 63 (47.7%) developed irAEs. We looked at the two groups' clinical features and found that the two groups were statistically different in age ≥ 65 years, Ki-67 index, white blood cell count, neutrophil count, and regulatory T cell (Treg) count (all P < 0.05). Multivariate logistic regression analysis showed that Treg count was a protective factor affecting irAEs occurrence (P = 0.030). The ROC curve indicated that Treg + Ki-67 + age (≥ 65 years) combined could predict irAEs well (area under the curve = 0.753, 95% confidence interval: 0.623-0.848, P = 0.001). Results of the Kaplan-Meier survival curve showed that progression-free survival (PFS) was longer in the irAEs group than in the non-irAEs group (P = 0.001). Cox proportional hazard regression analysis suggested that the occurrence of irAEs was an independent factor for PFS (P = 0.006). The number of Treg cells is a separate factor that affects irAEs in advanced gastric cancer patients receiving PD-1 inhibitor immunotherapy. irAEs can affect the patients' PFS and result in longer PFS. Treg + Ki-67 + age (≥ 65 years old) combined can better predict the occurrence of adverse reactions.

Effect of galectin-1 on prognosis and responsiveness of immune checkpoint plus tyrosine kinase inhibition in renal cell carcinoma.

In renal cell carcinoma (RCC), no clinically available biomarker has been utilized for checkpoint inhibitor immunotherapy (IO) + tyrosine kinase inhibitor (TKI) combinations. Galectin-1 overexpression is found in tumors, with potential immune-regulating roles. RNA-sequencing was performed in two cohorts of RCC treated with IO/TKI combination therapy (ZS-MRCC, JAVELIN-101). Immunohistochemistry and flow cytometry were performed to investigate immune cell infiltration and function in the tumor microenvironment of RCC. The RECIST criteria were used to define response and progression-free survival (PFS). Galectin-1 expression was elevated in RCC with higher stage (p < 0.001) and grade (p < 0.001). Galectin-1 expression was also elevated in non-responders of IO/TKI therapy (p = 0.047). High galectin-1 was related with shorter PFS in both ZS-MRCC cohort (p = 0.036) and JAVELIN-101 cohort (p = 0.005). Multivariate Cox analysis defined galectin-1 as an independent factor for PFS (HR 2.505; 95% CI 1.116-5.622; p = 0.026). In the tumor microenvironment, high galectin-1 was related with decreased GZMB+CD8+ T cells (Speraman's ρ = -0.31, p = 0.05), and increased PD1 + CD8+ T cells (Speraman's ρ = 0.40, p = 0.01). Besides, elevated number of regulatory T cells (p = 0.039) and fibroblasts (p = 0.011) was also found in high galectin-1 tumors. Finally, a random-forest score (RFscore) was built for predicting IO/TKI benefit. IO/TKI therapy showed benefit only in low-RFscore patients (HR 0.489, 95% CI 0.358-0.669, p < 0.001), rather than high-RFscore patients (HR 0.875, 95% CI 0.658-1.163, p = 0.357). High galectin-1 indicated therapeutic resistance and shorter PFS of IO/TKI therapy. High galectin-1 also indicated CD8+ T cell dysfunction. High galectin-1 could be applied for patient selection of IO/TKI therapy in RCC.

Nomograms combining computed tomography-based body composition changes with clinical prognostic factors to predict survival in locally advanced cervical cancer patients.

To explore the value of body composition changes (BCC) measured by quantitative computed tomography (QCT) for evaluating the survival of patients with locally advanced cervical cancer (LACC) underwent concurrent chemoradiotherapy (CCRT), nomograms combined BCC with clinical prognostic factors (CPF) were constructed to predict overall survival (OS) and progression-free survival (PFS). Eighty-eight patients with LACC were retrospectively selected. All patients underwent QCT scans before and after CCRT, bone mineral density (BMD), subcutaneous fat area (SFA), visceral fat area (VFA), total fat area (TFA), paravertebral muscle area (PMA) were measured from two sets of computed tomography (CT) images, and change rates of these were calculated. Multivariate Cox regression analysis showed ΔBMD, ΔSFA, SCC-Ag, LNM were independent factors for OS (HR = 3.560, 5.870, 2.702, 2.499, respectively, all P < 0.05); ΔPMA, SCC-Ag, LNM were independent factors for PFS (HR = 2.915, 4.291, 2.902, respectively, all P < 0.05). Prognostic models of BCC combined with CPF had the highest predictive performance, and the area under the curve (AUC) for OS and PFS were 0.837, 0.846, respectively. The concordance index (C-index) of nomograms for OS and PFS were 0.834, 0.799, respectively. Calibration curves showed good agreement between the nomograms' predictive and actual OS and PFS, decision curve analysis (DCA) showed good clinical benefit of nomograms. CT-based body composition changes and CPF (SCC-Ag, LNM) were associated with survival in patients with LACC. The prognostic nomograms combined BCC with CPF were able to predict the OS and PFS in patients with LACC reliably.

Pre-treatment 18f-FDG PET/CT for Assessing and Predicting Bone Marrow Involvement in Patients with Newly Diagnosed Peripheral T-Cell Lymphoma

Objective: To explore the value of 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) in assessing and predicting bone marrow involvement (BMI) in patients with newly diagnosed peripheral T-cell lymphoma (PTCL) prior to treatment. Methods: This retrospective study included 201 eligible patients of PTCL who received bone marrow biopsy (BMB) and PET/CT between January 2017 and December 2022. Extra subgroup analysis was designed considering the variation of avidity of FDG in different distinct entities. The status of bone marrow (BM) by PET was assessed using a visual examination and a quantitative index (the highest SUV of BM divided by the mean SUV of the liver [M/L]). Prognostic value of BM findings was also evaluated regarding progression free survival (PFS) and overall survival (OS). Results: The sensitivity and specificity of PET/CT for patients with confirmed PTCL by BMB were 43.2% and 90.2%, respectively. As for subgroup analysis, the kappa value reflecting the agreement between BMB and visual analysis in angioimmunoblastic T-cell lymphoma (AITL), peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), anaplastic large cell lymphoma (ALCL) as well as nodal T-follicular helper (TFH) cell lymphoma (PTCL-TFH) was 0.315, 0.307, 0.426 and 0.581, respectively. (Give the number of cases in each lymphoma group) PET score was an independent factor for PFS (P =0.011) but not for OS (P =0.840). In addition, 25 patients with stage I to II disease had no evidence of BMI by either PET/CT or BMB. Image-guided biopsy was also recommended when PET/CT showed a focal FDG uptake outside the iliac crest. Quantitative analysis revealed the differences in the two-level of M/L; however, they were not statistically significant for both PFS and OS (P =0.246 and P =0.227). Conclusion: PET/CT has a complementary role in assessing BMI and prognosis in PTCL patients.

Immune checkpoint inhibitors combined with or without radio(chemo)therapy for locally advanced or recurrent/metastatic esophageal squamous cell carcinoma

ObjectiveThis study was designed to investigate the efficacy and prognostic factors for immune checkpoint inhibitors (ICIs) combined with or without radio(chemo)therapy and to evaluate their toxicity in patients with locally advanced or recurrent/metastatic esophageal squamous cell carcinoma (LA/RM ESCC).MethodsIn this study, 198 patients with locally advanced or recurrent/metastatic (LA/RM) ESCC who received ICIs combined with or without radiotherapy/chemotherapy in the Department of Radiotherapy of the Fourth Hospital of Hebei Medical University were retrospectively analyzed. Univariate and multivariate analyses were performed to determine the prognostic factors for overall survival (OS) and progression free survival (PFS). The factors affecting treatment response and the occurrences of treatment-related adverse events (trAEs) were analyzed.ResultsThe median OS and PFS were 30.4 months (95% confidence interval [CI] 15.1–45.7 months) and 15.3 months (95% CI 12.8–17.8 months), respectively. Univariate and multivariate analysis showed that the number of ICI cycles, the intervention of radiotherapy and dysphagia were independent factors affecting OS (Hazard ratio [HR] = 0.39, 2.043 and 0.365, respectively; P = 0.018, 0.001 and 0.032, respectively). The intervention of radiotherapy was an independent factor for PFS (hazard ratio [HR] = 18.149, P = 0.013). The median OS and PFS for patients who had complete response and partial response (Objective response, ORR) were 50.8 months (95% CI 25.8–75.7 months) and 20.5 months (95% CI 14.1–27.0), respectively, which were significantly higher than those in the non-ORR group (OSnon-ORR:17.5 months, 95% CI 14.0–21.0; χ2 = 13.881, P < 0.001; PFSnon-ORR: 12.1 months, 95% CI 10.1–14.1, χ2 = 10.676, P = 0.001). The intervention of radiotherapy could improve treatment response (χ2 = 47.725, P = 0.000). In entire study population, 83 patients (41.9%) had ≥ grade 2 trAEs.ConclusionsICIs combined with radiotherapy/chemotherapy are safe and effective in LA/RM ESCC patients. Intervention of radiotherapy, the number of immunotherapy cycles and occurrence of dysphagia affecting the overall survival of LR/RM ESCC patients. Intervention of radiotherapy was an independent prognosis factor for OS and PFS and associated with better treatment response.

Analysis of Baseline Serum Lipid Profile for Predicting Clinical Outcomes of Patients with Extensive-Stage Small Cell Lung Cancer.

Serum lipids were reported to be the prognostic factors of various cancers, but their prognostic value in small cell lung cancer (SCLC) patients remains unclear. This study investigated the relationship between lipid profiles and clinical outcomes in extensive-stage (ES) SCLC by establishing a predictive risk classification model. We retrospectively analyzed the prognostic values of pretreatment serum lipids and their derivatives in patients with a confirmed diagnosis ES-SCLC. Independent factors of progression-free survival (PFS) were determined by univariate and multivariate cox analysis. Then, prognostic nomograms were established, of which predictive performance was evaluated by concordance index (C-index), calibration curves, receiver operating characteristic (ROC) curves, and decision curve analyses (DCA). A total of 158 patients was included in this study. Four optimal PFS-related factors, total cholesterol (TC) ≥ 5.30, high-density lipoprotein cholesterol (HDL-C) > 1.30, triglycerides (TG)/HDL-C > 2.18, and ki67 expression > 70%, were included to construct the predictive nomogram. The C-indexes in training and validation sets were 0.758 and 0.792, respectively. ROC curves, calibration plots, and DCA all suggested favorable discrimination and predictive ability. Besides, the nomogram also performed better predictive ability than ki67 expression. Nomogram-related risk score divided the patients into two groups with significant progression disparities. The promising prognostic nomogram based on lipid parameters could help clinicians to conveniently and accurately evaluate the prognosis of ES-SCLC patients and identify high-risk groups, so as to formulate individualized therapeutic regimens and follow-up strategies in time.

MINIMAL RESIDUAL DISEASE STATUS IMPROVED THE RESPONSE EVALUATION IN PATIENTS WITH WALDENSTRöM’S MACROGLOBULINEMIA

Minimal residual disease (MRD) has been recognized as an important prognostic factor for survival in hematological malignancies. However, the prognostic value of MRD in Waldenström’s macroglobulinemia (WM) remains largely unexplored. We analyzed 108 newly diagnosed WM patients receiving systematic therapy and assessed MRD by multiparameter flow cytometry (MFC) in the bone marrow. At best response, 34 patients (31.5%) achieved undetectable MRD (uMRD). Hemoglobin > 115 g/L (p = 0.03), serum albumin >35 g/L (p = 0.01), β2-MG ≤ 3 mg/L (p = 0.03), and low-risk International Prognostic Scoring System for WM (IPSSWM) stage (p < 0.01) were associated with a higher rate of uMRD. Improvements in IgM (p < 0.01) and hemoglobin (p = 0.03) were more evident in uMRD patients compared with MRD-positive patients. The 3-year progression-free survival (PFS) was better for uMRD patients compared with those MRD-positive patients (96.2% vs. 52.8%; p = 0.0012). Landmark analysis also showed that uMRD patients had a better PFS than MRD-positive patients after 6 and 12 months. Patients who achieved partial response (PR) and uMRD had a 3-year PFS of 100%, which was significantly higher than that patients with MRD-positive PR (62.6%, p = 0.029). Multivariate analysis showed that MRD positivity was an independent factor for PFS (HR 2.55, p = 0.03). Moreover, the combination of the 6th International Workshop on WM assessment (IWWM-6 Criteria) and MRD had a higher 3-year AUC compared with the IWWM-6 criteria only (0.71 vs. 0.67). MRD based on MFC was an independent prognostic factor for survival in WM, which could improve the precision of response evaluation, especially for patients who had obtained PR. Keywords: diagnostic and prognostic biomarkers, indolent non-Hodgkin lymphoma No conflicts of interests pertinent to the abstract.

Circulating tumor cells (CTCs) and hTERT gene expression in CTCs for radiotherapy effect with lung cancer

BackgroundCirculating tumor cells (CTCs) are important biological indicators of the lung cancer prognosis, and CTC counting and typing may provide helpful biological information for the diagnosis and treatment of lung cancer.MethodsThe CTC count in blood before and after radiotherapy was detected by the CanPatrol™ CTC analysis system, and the CTC subtypes and the expression of hTERT before and after radiotherapy were detected by multiple in situ hybridization. The CTC count was calculated as the number of cells per 5 mL of blood.ResultsThe CTC positivity rate in patients with tumors before radiotherapy was 98.44%. Epithelial–mesenchymal CTCs (EMCTCs) were more common in patients with lung adenocarcinoma and squamous carcinoma than in patients with small cell lung cancer (P = 0.027). The total CTCs (TCTCs), EMCTCs, and mesenchymal CTCs (MCTCs) counts were significantly higher in patients with TNM stage III and IV tumors (P < 0.001, P = 0.005, and P < 0.001, respectively). The TCTCs and MCTCs counts were significantly higher in patients with an ECOG score of > 1 (P = 0.022 and P = 0.024, respectively). The TCTCs and EMCTCs counts before and after radiotherapy affected the overall response rate (ORR) (P < 0.05). TCTCs and ECTCs with positive hTERT expression were associated with the ORR of radiotherapy (P = 0.002 and P = 0.038, respectively), as were TCTCs with high hTERT expression (P = 0.012). ECOG score (P = 0.006) and post-radiation TCTCs count (P = 0.011) were independent factors for progression-free survival (PFS) and TNM stage (P = 0.054) and pre-radiation EMCTCs count (P = 0.009) were independent factors of overall survival (OS).ConclusionThis study showed a high rate of positive CTC detection in patients with lung cancer, and the number, subtype, and hTERT-positive expression of CTCs were closely related to patients’ ORR, PFS, and OS with radiotherapy. EMCTCs, hTERT-positive expression of CTCs are expected to be important biological indicators for predicting radiotherapy efficacy and the prognosis in patients with lung cancer. These results may be useful in improving disease stratification for future clinical trials and may help in clinical decision-making.

An elevated preoperative cholesterol-to-lymphocyte ratio predicts unfavourable outcomes in colorectal cancer liver metastasis patients receiving simultaneous resections: a retrospective study

BackgroundTo explore the clinical prognostic utility of the preoperative cholesterol-to-lymphocyte ratio (CLR) in outcomes for colorectal cancer liver metastasis (CRLM) patients receiving simultaneous resection of the primary lesion and liver metastases.MethodsA total of 444 CRLM patients receiving simultaneous resections were enrolled. The optimal cut-off value for CLR was determined using the highest Youden’s index. Patients were divided into the CLR < 3.06 group and the CLR≥3.06 group. Propensity score matching analysis (PSM) and the inverse probability of treatment weighting (IPTW) method were conducted to eliminate bias between the two groups. The outcomes included short-term outcomes and long-term outcomes. Kaplan–Meier curves and log-rank tests were used to analyse progression-free survival (PFS) and overall survival (OS).ResultsIn the short-term outcome analysis, after 1:1 PSM, 137 patients were distributed to the CLR < 3.06 group and CLR≥3.06 group. No significant difference was noted between the two groups (P > 0.1). Compared with patients with CLR < 3.06, patients with CLR≥3.06 had comparable operation times (320.0 [272.5–421.0] vs. 360.0 [292.5-434.5], P = 0.088), blood loss (200.0 [100.0-400.0] vs. 200.0 [150.0-450.0], P = 0.831), postoperative complication rates (50.4% vs. 46.7%, P = 0.546) and postoperative ICU rates (5.8% vs. 11.7%, P = 0.087). In the long-term outcome analysis, Kaplan–Meier analysis showed that compared with patients with CLR < 3.06, patients with CLR≥3.06 had worse PFS (P = 0.005, median: 10.2 months vs. 13.0 months) and OS (P = 0.002, median: 41.0 months vs. 70.9 months). IPTW-adjusted Kaplan–Meier analysis showed that the CLR≥3.06 group had worse PFS (P = 0.027) and OS (P = 0.010) than the CLR < 3.06 group. In the IPTW-adjusted Cox proportional hazards regression analysis, CLR≥3.06 was an independent factor for PFS (HR = 1.376, 95% CI 1.097–1.726, P = 0.006) and OS (HR = 1.723, 95% CI 1.218–2.439, P = 0.002). IPTW-adjusted Cox proportional hazards regression analysis including postoperative complications, operation time, intraoperative blood loss, intraoperative blood transfusion and postoperative chemotherapy revealed that CLR≥3.06 was an independent factor for PFS (HR = 1.617, 95% CI 1.252–2.090, P < 0.001) and OS (HR = 1.823, 95% CI 1.258–2.643, P = 0.002).ConclusionsThe preoperative CLR level predicts unfavourable outcomes in CRLM patients receiving simultaneous resection of the primary lesion and liver metastases and should be taken into consideration when developing treatment and monitoring strategies.

Prognostic Value of Absolute Lymphocyte Count in Patients with Advanced Renal Cell Carcinoma Treated with Nivolumab Plus Ipilimumab

Nivolumab and ipilimumab (NIVO + IPI) is standard therapy for patients with advanced renal cell carcinoma (RCC). Absolute lymphocyte count (ALC) is a valuable prognostic factor in patients with various cancers treated with immune checkpoint inhibitors. Herein, we determined the prognostic value of pretreatment ALC in advanced RCC patients treated with NIVO + IPI as first-line therapy. Data from 46 advanced RCC patients treated with NIVO + IPI between September 2018 and August 2022 were retrospectively reviewed and analyzed. Median progression-free survival (PFS) and overall survival (OS) were significantly shorter in patients with low than high ALC (PFS: p = 0.0095; OS: p = 0.0182). Multivariate analysis suggested that prior nephrectomy [hazard ratio (HR) = 3.854, 95% confidence interval (CI) = 1.433-10.359, p = 0.0075] and pretreatment ALC (HR = 2.513, 95% CI = 1.119-5.648, p = 0.0257) were independent factors for PFS. Our new prognostic ALNx model based on ALC and prior nephrectomy suggested that the poor-risk group was a predictor of significantly worse PFS (p < 0.0001) and OS (p = 0.0016). Collectively, the developed ALNx model may be a novel predictor of response in advanced RCC patients treated with NIVO + IPI.

Clinical relevance of high-risk cytogenetic abnormalities and the second revision of the International Staging System (R2-ISS) in patients with multiple myeloma in clinical practice.

High-risk cytogenetic abnormalities (HRCAs) are the most critical factor affecting prognosis in multiple myeloma (MM). However, the clinical significance of HRCAs in routine practice has not been fully elucidated. We retrospectively analyzed clinical features and outcome in 60 newly diagnosed MM patients with or without HRCAs including t(4;14), t(14;16), del(17p), and 1q gain/amplification. The median age was 71years (range, 35-90). Abnormalities with t(4;14), t(14;16), del(17p), and 1q gain/amplification were found in 10, 1, 6, and 21/14 patients, respectively, and 10 patients had ≥ 2 HRCAs. Patients with HRCAs exhibited progressive clinical features such as anemia, high β2-microglobulin, and high LDH. Symptomatic relapse was more common in patients with HRCAs. The median progression-free survival (PFS) by number of HRCAs (0, 1, and ≥ 2) was 51.7, 21.4, and 26.1months (p = 0.011), and the median overall survival (OS) was not reached, 60.7, and 46.8months (p = 0.045), respectively. Multivariate analysis revealed that HRCAs were an independent factor for PFS. Accordingly, the second revision of International Staging System (R2-ISS), which incorporates HRCA scores, was more useful for prognostic stratification (p = 0.0023). These results suggest that presence of multiple HRCAs including 1q gain/amplification is associated with advanced stage and poor prognosis in clinical practice as well.

Is t(11;14)(q13;q32) good or bad for newly diagnosed multiple myeloma?

Is t(11;14)(q13;q32) good or bad for newly diagnosed multiple myeloma?

Radiotherapy Enhance the Immune Checkpoint Inhibitors Efficacy in Advanced Liver Cancer

<h3>Purpose/Objective(s)</h3> Many patients with advanced liver cancer receiving immunotherapy show primary or acquired resistance. Radiotherapy (RT) is an integral component in the treatment of solid cancers, including HCC. Radiation mediates localized tumor killing and further leads to increased tumor antigen release, improving antigen presentation and T-cell infiltration, thereby potentiating the action of immune checkpoint inhibitors (ICIs). Here we aim to investigate the efficacy and safety of radiation therapy (RT) plus ICIs in advanced liver cancer. <h3>Materials/Methods</h3> Of the 180 patients enrolled from August 2018 to June 2021, 87 patients were treated with the combination of RT and ICIs (RT-ICIs cohort); 93 patients were given ICIs therapy (ICIs cohort). Radiotherapy was conducted within 60 days or concurrently of starting programmed death receptor or ligand-1 (PD-1 or PD-L1) inhibitor therapy. Propensity-score matched estimates were used to reduce bias when evaluating the clinical outcomes. <h3>Results</h3> In the matched cohorts (49 pairs), the median progression-free survival (PFS) and overall survival (OS) in the RT-ICIs cohort were significantly longer than those in the ICIs cohort (PFS, 8.1 vs. 3.0 months, <i>p</i> < 0.001; OS, 21.7 vs. 13.3 months, <i>p</i> = 0.023). The RT-ICIs cohort also achieved higher objective response rate (ORR) and disease control rate (DCR) than those in the ICIs cohort (ORR 49.0% vs. 22.4%, <i>p</i> = 0.006; DCR 71.4% vs. 32.7%, <i>p</i> < 0.001). At multivariate analysis, RT-ICIs treatment was an independent factor for PFS (hazard ratio [HR] 0.45; 95% CI 0.294-0.668; <i>p</i> < 0.001) and OS (HR 0.530; 95% CI 0.287-0.976; <i>p</i> = 0.042). No significant differences in toxic effects between cohorts were observed in the analysis. <h3>Conclusion</h3> Radiotherapy enhances the ICIs efficacy in patients with advanced liver cancer by improving control of the systemic disease without an increase in toxic effects. Since this is a small retrospective study, a prospective randomized trial is ongoing to validate this finding (ClinicalTrials.gov identifier: NCT03857815).

Analysis of Lenvatinib's Efficacy against Intermediate-Stage Unresectable Hepatocellular Carcinoma.

Transarterial chemoembolization (TACE) has been the standard treatment for intermediate-stage, unresectable hepatocellular carcinoma (u-HCC). However, with recent advances in systemic therapy and the emergence of the concept of TACE-refractory or -unsuitable, the effectiveness of systemic therapy, as well as TACE, has been demonstrated for patients judged to be TACE-refractory or -unsuitable. In this study, the efficacy of lenvatinib and its combination with TACE after lenvatinib was investigated in 140 patients with intermediate-stage u-HCC treated with lenvatinib mainly because of being judged to be TACE-refractory or -unsuitable. Median overall survival (OS) and progression-free survival (PFS) were 24.4 and 9.0 months, respectively, indicating a good response rate. In multivariate analysis, modified albumin-bilirubin (mALBI) grade and up to seven criteria were identified as independent factors for OS, and mALBI grade and tumor morphology were identified as independent factors for PFS. While 95% of all patients were TACE-refractory or -unsuitable, the further prognosis was prolonged by the combination with TACE after lenvatinib initiation. These findings suggest that systemic therapy should be considered for intermediate-stage u-HCC, even in patients judged to be TACE-refractory or -unsuitable. The use of TACE after the start of systemic therapy may further improve prognosis.

Proton Beam Therapy for Treatment-Naïve Hepatocellular Carcinoma and Prognostic Significance of Albumin-Bilirubin (ALBI) Grade.

Simple SummaryProton beam therapy (PBT) has not been generally recommended as an initial treatment for hepatocellular carcinoma (HCC) due to the insufficiency of data on PBT for treatment-naïve HCC until now, and albumin-bilirubin (ALBI) grade has been shown to be an effective assessment of liver dysfunction and more discriminatory for survival than the Child–Pugh classification. This study evaluated the efficacy of PBT as first-line treatment in treatment-naïve HCC and assessed the prognostic significance of ALBI grade in these patients. Our findings showed that PBT could result in comparable local tumor control and survival outcomes in treatment-naïve HCC patients to those of other recommended first-line treatments, with a safe toxicity profile compared to our institutional cohort data and previous other studies, and ALBI grade and tumor stage were independent predicting factors for overall survival.To evaluate the efficacy of proton beam therapy (PBT) as an initial treatment in treatment-naïve hepatocellular carcinoma (HCC) patients and to assess the prognostic significance of albumin-bilirubin (ALBI) grade, 46 treatment-naïve HCC patients treated with PBT were analyzed. The ALBI grade distribution was grade 1 in 11 (23.9%) patients, grade 2 in 34 (73.9%) patients, and grade 3 in 1 (2.2%) patient. The median duration of follow-up was 56.5 months (95% confidence interval [CI], 48.2–64.7). Among the 46 patients, disease progression was observed in 23 (50%) patients: local progression in 3 (6.5%) patients; intrahepatic progression in 22 (47.8%); and extrahepatic progression in 5 (10.9%). The 5-year freedom from local progression (FFLP), progression-free survival (PFS), and overall survival (OS) rates were 92.7% (95% CI, 84.7–100.7), 43.3% (95% CI, 28.2–58.4), and 69.2% (95% CI, 54.9–83.5), respectively. In multivariate analysis, there were no independent factors for FFLP (p > 0.05 each), but tumor stage and ALBI grade were independent factors for PFS and OS (p < 0.05 each). PBT could result in comparable OS in treatment-naïve HCC patients to other recommended first-line treatments, and ALBI grade, in addition to tumor stage, could be useful for predicting OS.

Effectiveness and Safety of PD-1 Inhibitor Monotherapy for Elderly Patients with Advanced Non-Small Cell Lung Cancer: A Real-World Exploratory Study.

Background Immunotherapy represented by PD-1 blockades had become the standard of care for advanced non-small cell lung cancer (NSCLC) gradually. Unfortunately, several PD-1 inhibitor-related studies excluded elderly patients with NSCLC over 75 years of age, resulting in relatively limited evidence regarding the efficacy and safety of PD-1 in elderly patients with NSCLC clinically. Objective This study aimed to identify the effectiveness and safety of PD-1 blockade monotherapy among elderly patients with advanced NSCLC. Methods Elderly patients with advanced NSCLC (≥65 years) who received PD-1 blockade monotherapy from September 2018 to December 2021 were screened retrospectively, and a total of 68 elderly patients with NSCLC were eligible for inclusion ultimately. The PD-1 blockades in the study were the available PD-1 monoclonal antibodies that had been approved for marketing in China, including camrelizumab, sintilimab, pembrolizumab, and nivolumab. The effectiveness and safety of the patients was collected retrospectively. Additionally, the correlation between prognosis and baseline characteristic subgroups was analyzed to identify the potential risk factors for progression-free survival (PFS). Results The median age of the 68 elderly patients with advanced NSCLC was 73 years (range: 65–82 years). Best overall response during PD-1 blockade administration suggested that no patients were found with complete response, partial response was found in 14 patients, stable disease was noted in 29 patients, and 25 patients had progressive disease, yielding an objective response rate (ORR) of 20.6% (95%CI: 11.7%–32.1%) and a disease control rate (DCR) of 63.2% (95%CI: 50.7%–74.6%). Furthermore, prognostic analysis exhibited that the median progression-free survival (PFS) of the 68 patients with advanced NSCLC was 3.5 months (95%CI: 2.4–4.6) and the median overall survival (OS) was 10.5 months (95%CI: 6.3–14.7). Additionally, a total of 48 patients were observed with the treatment-related adverse reaction (70.6%) of the 68 elderly patients with NSCLC, and the incidence of grade 3 or above adverse reactions was 16.2%. Specifically, the most common adverse reactions were fatigue, diarrhea, rash, and abnormal liver function with the incidence of 25.0%, 22.1%, 16.2%, and 14.7%, respectively. Exploratory analysis between PFS and baseline characteristic subgroups suggested that ECOG performance status and number of metastatic lesions might be independent factors for PFS. Conclusion PD-1 blockade monotherapy exhibited potential effectiveness and acceptable toxicity for elderly patients with NSCLC. ECOG performance status and number of metastatic lesions might be potential risk factors to predict the PFS of elderly patients with advanced NSCLC.

The Usefulness of Machine Learning-Based Evaluation of Clinical and Pretreatment [18F]-FDG-PET/CT Radiomic Features for Predicting Prognosis in Hypopharyngeal Cancer.

To examine whether the machine learning (ML) analyses using clinical and pretreatment 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography ([18F]-FDG-PET)-based radiomic features were useful for predicting prognosis in patients with hypopharyngeal cancer. This retrospective study included 100 patients with hypopharyngeal cancer who underwent [18F]-FDG-PET/X-ray computed tomography (CT) before treatment, and these patients were allocated to the training (n=80) and validation (n=20) cohorts. Eight clinical (age, sex, histology, T stage, N stage, M stage, UICC stage, and treatment) and 40 [18F]-FDG-PET-based radiomic features were used to predict disease progression. A feature reduction procedure based on the decrease of the Gini impurity was applied. Six ML algorithms (random forest, neural network, k-nearest neighbors, naïve Bayes, logistic regression, and support vector machine) were compared using the area under the receiver operating characteristic curve (AUC). Progression-free survival (PFS) was assessed using Cox regression analysis. The five most important features for predicting disease progression were UICC stage, N stage, gray level co-occurrence matrix entropy (GLCM_Entropy), gray level run length matrix run length non-uniformity (GLRLM_RLNU), and T stage. Patients who experienced disease progression displayed significantly higher UICC stage, N stage, GLCM_Entropy, GLRLM_RLNU, and T stage than those without progression (each, p<0.001). In both cohorts, the logistic regression model constructed by these 5 features was the best performing classifier (training: AUC=0.860, accuracy=0.800; validation: AUC=0.803, accuracy=0.700). In the logistic regression model, 5-year PFS was significantly higher in patients with predicted non-progression than those with predicted progression (75.8% vs. 8.3%, p<0.001), and this model was only the independent factor for PFS in multivariate analysis (hazard ratio = 3.22; 95% confidence interval = 1.03-10.11; p=0.045). The logistic regression model constructed by UICC, T and N stages and pretreatment [18F]-FDG-PET-based radiomic features, GLCM_Entropy, and GLRLM_RLNU may be the most important predictor of prognosis in patients with hypopharyngeal cancer.

The clinical features, treatment, and prognostic factors for peripheral T-cell lymphomas: A single-institution analysis of 240 Chinese patients.

This study aimed to analyze the clinical features, treatment, survival, and prognostic factors of Chinese patients with peripheral T-cell lymphoma (PTCL) excluding natural killer/T-cell lymphoma (NKTCL). Data on patients with newly diagnosed PTCLs between January 1, 2006 and December 31, 2017 at our hospital were retrospectively reviewed. Patients with NKTCL were excluded. A total of 240 patients were included. PTCL, not otherwise specified (PTCL-NOS), was the most frequent subtype (42.5%), followed by angioimmunoblastic T-cell lymphoma (AITL) (21.3%), anaplastic lymphoma kinase (ALK)-negative anaplastic large-cell lymphoma (ALK-ALCL) (16.7%), ALK-positive ALCL (ALK+ALCL) (10.8%) and others (8.8%). With a median follow-up of 81.1 months, the 5-year progression-free survival (PFS) and overall survival (OS) rates for all patients were 30.4% (95% CI 25.0%-37.0%) and 48.8% (95% CI 42.6%-55.7%), respectively. On multivariate analysis, no consolidative autologous stem cell transplantation (ASCT) and not achieving complete response after first-line chemotherapy retained independently prognostic value for inferior PFS and OS. Besides, bone marrow involvement and serum albumin level were independent factors for PFS, and Eastern Cooperative Oncology Group performance status ≥2 was significantly predictive of inferior OS. Compared with PTCL-NOS, significantly superior PFS and OS were observed for ALK+ALCL and ALK-ALCL. The survival outcomes with current treatment for most PTCL subtypes are still unsatisfactory. Prospective randomized studies are needed to establish the value of consolidative ASCT in PTCL, and novel therapeutic approaches should be explored.