Independent Prognostic Factor For Survival Research Articles

Bronchial artery chemoembolization with drug-eluting beads versus bronchial artery infusion followed by polyvinyl alcohol particles embolization for advanced squamous cell lung cancer: A retrospective study

PurposeTo analyze the efficacy and safety of bronchial arterial embolization (BACE) with drug-eluting beads (DEB) versus bronchial artery infusion (BAI) followed by polyvinyl alcohol (PVA) particle embolization for the treatment of advanced squamous cell lung cancer after the failure of systemic therapy. MethodThirty-six patients with advanced squamous cell lung cancer who underwent bronchial arterial interventional therapy were included in this retrospective study. The DEB group (n = 20) was treated with nedaplatin and DEB loaded with gemcitabine, and the PVA group (n = 16) BAI with nedaplatin and gemcitabine followed by embolization with PVA particles. The treatment efficacy and complications were analyzed. ResultsThe technical success rate was 100 %. The two groups were followed up for a median period of 8.9 months. The mean overall survival (OS) in the DEB group was 12.6 months (95 % CI:9.99–15.21), which was significantly longer than 8.14 months (95 % CI:6.07–10.2) in the PVA group (p = 0.007). The median progression-free survival (PFS) in the DEB group was 4.3 months (95 % CI:2.33–6.27), significantly longer than 3.2 months (95 % CI:2.55–3.85) in the PVA group (p = 0.030). The objective response rate (ORR) six months after the procedure was 50 % in the DEB group and 12.5 % in the PVA group. In the univariate and multivariate analyses, DEB-BACE was an independent prognostic factor for survival. Only grade 1 adverse events like fever, chest pain, and cough were seen. ConclusionsDEB-BACE may be a good choice for patients with advanced lung squamous cell carcinoma, as it could prolong OS and PFS without increasing adverse events.

The Characteristics of Breast Cancer Patients and Survival Analysis in the Southeast of Iran: A Retrospective Cohort Study

Background: Breast cancer is the most common cancer in women, with different survival rates depending on the patients’ characteristics. Objectives: This study aimed to evaluate breast cancer patients’ characteristics and survival rates in the southeast of Iran. Methods: The recorded data of breast cancer patients treated were collected from 2004 to 2020 in the Radiation Oncology Department of Kerman University of Medical Sciences, Iran. Overall survival (OS) was estimated using the Kaplan-Meier method. The log-rank test was used to compare OS based on various factors. Three modeling strategies were considered to examine the patients’ survival using multiple Cox regression models. Results: The study included 309 patients who met the inclusion criteria; 153 (49.5%) were under 51 years of age. Luminal A intrinsic subtype accounted for 18.8% of cancer patients. Five- and 10-year OS rates were 86% and 63%, respectively. Five- and 10-year disease-free survival (DFS) rates for nonmetastatic patients were 82% and 60%, respectively. Multiple Cox regression showed that the percentage of the involved dissected lymph nodes, group stage, T-stage, M-stage, locoregional recurrence, and luminal subtype were independent prognostic factors for survival. Conclusions: Based on the results, the percentage of breast cancer patients under 50 years old is higher in the southeast of Iran compared to Western countries. In addition, the prevalence of the luminal A subtype is lower than in other regions. The survival results were consistent with other studies.

Safety and efficacy of stereotactic ablative brachytherapy as a salvage therapy for recurrent chest wall cancer: A retrospective, multicenter study.

To evaluate the safety and efficacy of stereotactic ablative brachytherapy (SABT) as a salvage therapy for patients with recurrent chest wall cancer (rCWC) who have previously received external beam radiotherapy (EBRT) or surgery. Between November 2013 and October 2020, a total of 130 patients (including 75 men with a median age of 63 years) with rCWC treated with SABT were enrolled in this multicenter retrospective study. There were 97 cases of non-small-cell lung carcinoma, 24 cases of breast cancer, and 9 cases of thymic cancer. Of the patients included, 102 patients previously received surgery and 58 patients received EBRT, with systemic treatment progressing after recurrence. None of them were suitable or refused to undergo salvage EBRT or surgery again. During the 22 (4-70)-month median patient follow-up, 59 patients died. The local control (LC) rates at 6, 12, 24, and 36 months were 88.3%, 74.3%, 50.4%, and 36.7%, respectively. The 1-, 2- and 3-year survival rates were 85%, 56%, and 42%, respectively. The median overall survival was 26 months (95% CI, 18.9-33.1 months). The pain relief rate was 81%, and the median to remission time was 10 days. Univariate and multivariate analyses showed that independent prognostic factors for LC included tumor size and postoperative D90. On the other hand, independent prognostic factors for survival include the Karnofsky performance status (KPS) score, tumor size, and D90 19 patients (14.6%) developed grade I/II skin reaction complications. No grade III or severer complications occurred. SABT is safe and effective as a salvage therapy for rCWC following EBRT/surgery. For patients with a KPS score greater than 80, prescribed dose greater than 130 Gy, and tumor size less than 4 cm may bring better results.

Evaluation of the clinical characteristics and prognostic factors of gastrointestinal non-Hodgkin lymphoma based on anatomical sites and histological subtype

Background This study aimed to analyze the clinical characteristics and prognostic factors of patients with non-Hodgkin lymphoma (NHL) in the gastrointestinal tract. Methods This study investigated patients (n = 456) with gastrointestinal tract NHL who had been initially treated in our hospital between January 2018 and December 2021. We compared clinical characteristics and prognostic factors according to the anatomic site of involvement and histologic subtypes. Results Gastrointestinal tract involvement was more common in B-cell than T-cell lymphomas (91.7% versus 8.3%). The intestine (n = 237) involvement was more common than the stomach (n = 219). Patients with T-cell lymphoma were more likely to present with advanced disease and B symptoms than B-cell lymphoma. Subgroup survival analysis was conducted for 358 patients whose follow‐up time was more than 2 years, we found that T-cell immunophenotype and elevated serum lactate dehydrogenase (LDH) were independent prognostic factors for survival. Patients with advanced disease were identified as risk factors for relapsed or refractory gastrointestinal tract NHL. Conclusions In our subgroup survival analysis, we found that the survival outcomes demonstrated no significant differences between the stomach and intestinal tract NHL. Serum LDH levels and histologic subtypes were independent prognostic factors for the survival of gastrointestinal tract NHL. Advanced diseases were considered risk factors for relapsed or refractory gastrointestinal tract NHL.

Low p16 Cytoplasmic Staining Predicts Poor Treatment Outcome in Patients with p16-Negative Locally Advanced Head and Neck Squamous Cell Carcinoma Receiving TPF Induction Chemotherapy.

Human papillomavirus (HPV) has been proven to be associated with head and neck squamous cell carcinoma (HNSCC), and diffuse p16 unclear staining is usually considered as HPV-positive. The aim of the current study was to investigate the role of p16 cytoplasmic staining in HNSCC prognosis. A total of 195 HNSCC patients who received docetaxel, cisplatin, and 5-fluouracil (TPF) induction chemotherapy followed by chemoradiotherapy were enrolled. The status of p16 cytoplasmic staining was determined using immunohistochemistry. The median follow-up was 26.0 months for the whole study population and 90.3 months for 51 living survivors. p16 cytoplasmic staining was low in 108 patients and high in 87 patients. Low expression of p16 cytoplasmic staining and primary tumor location in the oral cavity were both independent factors indicating a worse response rate to TPF induction chemotherapy in the univariate and multivariate analyses. The logistic regression model also showed that low expression of p16 cytoplasmic staining and clinical N2-3 status were independent prognostic factors for worse progression-free survival and overall survival. Our study showed that p16 cytoplasmic staining could predict the treatment response to TPF induction chemotherapy and is an independent prognostic factor of survival in HNSCC.

Pretreatment neutrophil to lymphocyte ratio as prognostic factor in metastatic breast cancer treated with cyclin dependent kinase 4/6 inhibitors.

Cyclin dependent kinase inhibitors (CdK4/6i) changed the course of hormone receptor positive (HR+) HER2 negative (HER2-) metastatic breast cancer (mBC). To date, no factors have been shown to predict response to CdK4/6i. Neutrophil-to-lymphocyte ratio (NLR), an indicator of the host systemic inflammatory response, is an independent prognostic factor for survival in cancers. We conducted this study to evaluate the impact of NLR on survival in mBC patients treated with first line CdK4/6i. All mBC patients treated with first line CdK4/6i between November 2015 and December 2019 were retrospectively included. The biomarker threshold was defined using ROC curves. We analyzed progression free survival (PFS), overall survival (OS), 12-month PFS and response rate according to NLR in univariable and multivariable analysis. A total of 126 patients treated with palbociclib (n=101), ribociclib (n=18) or abemaciclib (n=7) were included, with a median follow-up of 33 months [range: 2.9-57]. Median age was 65 years [29-86], 40% patients had good performance status (ECOG-PS 0). Most patients (71%) were included at the metastatic relapse stage and 29% had only bone metastases. Median PFS and median OS were 27 and 51 months, respectively. High NLR (≥ 2.53) was significantly associated with worse PFS (Hazard Ratio (HR)=0.50, CI95% = [0.32-0.79]) and worse OS (HR=0.45, [CI95%: 0.23-0.87]). In multivariable analysis, NLR and ECOG PS were independently factors associated with PFS (p=0.016 and p=0.001, respectively). High NLR was associated with worse PFS and OS in HR+ HER2- mBC patients treated with first line CdK4/6i. NLR is a reliable and inexpensive prognostic marker, easily accessible in routine clinical practice, which could help optimize the therapeutic strategy. These results need to be confirmed in larger prospective studies.

Prognostic Value of Controlling Nutritional Status Score in Advanced Hypopharyngeal Cancer.

The purpose of this study was to investigate the prognostic significance of the preoperative controlling nutritional status (CONUT) score in patients with resectable advanced hypopharyngeal cancer. This retrospective study included 113 advanced hypopharyngeal cancer patients who underwent curative resection in our hospital from 2013 to 2017. The association between the CONUT score and clinicopathological variables was evaluated. The association between CONUT score and survival was analyzed using Kaplan-Meier survival curves and Cox regression. The efficacy of the CONUT score and other immune-nutritional markers to predict prognosis was compared using a time-dependent receiver operating characteristic (ROC). Patients were divided into the high-CONUT score group (≥3) and the low-CONUT score group (≤2) according to ROC analysis. The CONUT score was associated with body mass index (p=0.047), monocyte (p=0.021), pharyngocutaneous fistula (p=0.045), flap repairment (p=0.034), tumor (T) classification (p=0.034), node (N) classification (p=0.036), subsite of tumor (p=0.035), and negative pathologic factors (p < 0.001). Tumor, node, metastasis (TNM) stage, negative pathologic factors, adjuvant radiotherapy, postoperative chemoradiotherapy, and CONUT score were independent prognostic factors for survival. Patients with a higher CONUT score had worse overall survival (OS) (hazard ratio: 2.76, 95% confidence interval [CI]: 1.44-5.29, p=0.002) and disease-free survival (hazard ratio: 2.51, 95% CI: 1.28-4.91, p=0.007). The area under the curve of the CONUT score (0.799) to predict 5-year OS wasgreater than those of Preoperative Nutritional Index (0.769), platelet-to-lymphocyte ratio (0.643), neutrophil-to-lymphocyte ratio (0.565), and lymphocyte-to-monocyte ratio (0.577). The CONUT score is a prognostic marker for patients with resectable advanced hypopharyngeal cancer. 3 Laryngoscope, 133:2613-2620, 2023.

Microwave ablation and synchronous transarterial chemoembolization combined with PD-1 inhibitor in patients with hepatocellular carcinoma following tyrosine kinase inhibitor intolerance.

To determine the safety and efficacy of microwave ablation (MWA) and synchronous transarterial chemoembolization (TACE) combined with or without PD-1 inhibitor in patients with hepatocellular carcinoma (HCC) following tyrosine kinase inhibitor (TKI) intolerance. This study retrospectively enrolled TKI-intolerant HCC patients who underwent MWA-TACE combined with PD-1 inhibitor (MTP) or MWA-TACE (MT) from January 2019 to June 2021. MWA and TACE were performed simultaneously, and PD-1 inhibitor was administered intravenously at a dose of 200 mg once every three weeks after MWA-TACE. Adverse events (AEs) related to treatment were recorded during the follow-up. Progression-free survival (PFS) and overall survival (OS) were compared between the two groups. A total of 87 patients were included and classified into the MTP group (n =42) and MT group (n=45). Complications related to MWA-TACE in the MTP group were similar to that in the MT group (21.4% vs. 24.4%, P = 0.738). Moreover, 35 (83.3%) patients had eighty-four AEs related to PD-1 inhibitor in the MTP group, and 8 (19.0%) patients developed grade 3. Patients who underwent MWA-TACE combined with PD-1 inhibitor had better PFS (median, 10.0 vs. 4.7 months, P < 0.001) and OS (median, 17.0 vs. 8.5 months, P < 0.001) than those who underwent MWA-TACE alone. Treatment method and Child-Pugh class were independent prognostic factors for survival in the univariate and multivariate analysis. MWA and synchronous TACE combined with PD-1 inhibitor might be a favorable treatment option in TKI-intolerant HCC patients.

Association between perineural infiltrations and delayed gastric emptying after Whipple procedure for periampullary tumours, and the relationship with other clinicopathological factors and overall survival.

Pancreaticoduodenectomy is a major procedure. Delayed gastric emptying (DGE) is a frequent postoperative complication that is attributed to several factors. To investigate the probable association between perineural infiltrations and DGE, and the effects on overall survival. A total of 123 patients who underwent pancreaticoduodenectomy were enrolled in the study. Factors like the presence of perineural infiltrations and post-operative DGE along with age, gender, presence of postoperative fistula, and grade of fistula and postoperative haemorrhage were analysed, and survival analyses were conducted. The presence of perineural infiltrations is statistically associated with DGE occurrence (p = 0.01). Moreover, the occurrence of DGE is statistically associated with male gender (p = 0.001), worse grade of postoperative fistula (p < 0.01), and the presence of postoperative haemorrhage (p = 0.03). There was no statistical association between the presence of perineural infiltrations and the other factors. Cox regression and Kaplan-Meier survival analyses showed that increased overall survival is associated with low age (p = 0.018 and p = 0.028, respectively), absence of perineural infiltrations (p = 0.005 and p = 0.003, respectively), better grade of postoperative fistula (p < 0.001), and absence of postoperative haemorrhage (p < 0.001). Multivariate analysis showed that independent prognostic factors for survival prognosis are perineural infiltrations, age, the presence of postoperative pancreatic fistula, and the presence of postoperative haemorrhage. This is the first study that proves a statistically significant association between the presence of perineural infiltrations and the occurrence of DGE. Moreover, perineural infiltrations are an important independent prognostic factor for overall survival, along with other clinical factors.

Patients with Lower Positive Lymph Nodes Ratio May Benefit from Preoperative Radiotherapy in Stage III Non-Small Cell Lung Cancer.

Although preoperative radiotherapy (PORT) is a promising therapeutic option for stage III non-small cell lung cancer (NSCLC), the efficacy of this treatment remains controversial. The positive lymph node ratio (PLNR) is recognized as an independent prognostic factor for survival. However, no previous studies have focused on the association between PLNR and PORT in stage III NSCLC. Data were collected from the Surveillance, Epidemiology and End Results (SEER) database, and all patients enrolled in this analysis were diagnosed during 2010-2015. The primary endpoint was overall survival (OS). Univariate and multivariate Cox regression analysis was used to identify factors associated with survival before and after case-control matching. PLNR was defined as the ratio of the number of positive lymph nodes to the total number of retrieved or examined lymph nodes. A cutoff value for PLNR was calculated using an X-tile model. Overall, 391 patients with PORT and 2814 patients without PORT were enrolled in this study. The cohort after 1:1 case-control matching included 322 patients who received PORT and 322 patients without PORT. PORT was not associated with a significant effect on OS (HR = 1.14; 95% CI: 0.91-1.43; P = 0.825). Multivariate Cox regression analysis showed that PLNR (P < 0.001) was independently associated with OS in patients with stage III NSCLC. An X-tile model was used to identify a cutoff value for PLNR: the risk of death was significantly lower in patients with PLNR ≤0.41 who received PORT than in those with PLNR >0.41 who received PORT (HR = 0.59; 95% CI: 0.38-0.91; P = 0.015). PLNR may be a prognostic factor for survival in patients with stage III NSCLC who undergo PORT. Lower PLNR is a predictor of better OS and thus warrants further study.

OPLAH Protein Expression Stratifies the Prognosis of Patients With Squamous Cell Carcinoma of the Esophagus.

Squamous cell carcinoma is one of the major subtypes of esophageal carcinoma, and the 5-year overall survival rate of esophageal squamous cell carcinoma patients who underwent curative treatment remains below 40%. We aimed to detect and validate the prognosticators of esophageal squamous cell carcinoma in patients who underwent radical esophagectomy. Comprehensive analysis of transcriptome and clinical data from The Cancer Genome Atlas revealed OPLAH as one of the differentially expressed genes between esophageal squamous cell carcinoma tissues and normal esophageal mucosa. OPLAH expression changes were significantly associated with a patient prognosis. OPLAH protein levels were further evaluated by immunohisto-chemistry in esophageal squamous cell carcinoma tissues (n=177) as well as in serum samples (n=54) using ELISA. OPLAH mRNA was significantly overexpressed in esophageal squamous cell carcinoma tissues compared to normal esophageal mucosa, and patients with high OPLAH mRNA expression have a significantly poorer prognosis, according to The Cancer Genome Atlas data. The high staining intensity of OPLAH protein in esophageal squamous cell carcinoma tissue clearly stratified patient prognosis. According to multivariable analysis, high OPLAH protein expression was an independent prognostic factor for survival after surgery. Pre-neoadjuvant chemotherapy serum OPLAH protein concentrations were significantly associated with clinical tumor depth and node positivity and, consequently, with advanced clinical stage. The serum OPLAH protein concentration was significantly decreased by neoadjuvant chemotherapy. OPLAH protein expression in cancerous tissue and serum may have clinical utility towards stratifying prognosis of patients with esophageal squamous cell carcinoma.

Identification of FKBP10 prognostic value in lung adenocarcinoma patients with surgical resection of brain metastases: A retrospective single-institution cohort study

ObjectiveTo explore the expression levels and clinical value of FKBP10 in lung adenocarcinoma brain metastases. DesignA retrospective single-institution cohort study. PatientsThe perioperative records of 71 patients with lung adenocarcinoma brain metastases who underwent surgical resection at the authors’ institution between November 2012 and June 2019 were retrospectively analyzed. MethodsThe authors evaluated FKBP10 expression levels using immunohistochemistry in tissue arrays of these patients. Kaplan-Meier survival curves were constructed, and a Cox proportional hazards regression model was used to identify independent prognostic biomarkers. A public database was used to detect FKBP10 expression and its clinical value in primary lung adenocarcinoma. ResultsThe authors found that the FKBP10 protein was selectively expressed in lung adenocarcinoma brain metastases. Survival analysis showed that FKBP10 expression (p = 0.02, HR = 2.472, 95% CI [1.156, 5.289]), target therapy (p < 0.01, HR = 0.186, 95% CI [0.073, 0.477]), and radiotherapy (p = 0.006, HR = 0.330, 95% CI [0.149, 0.731]) were independent prognostic factors for survival in lung adenocarcinoma patients with brain metastases. The authors also detected FKBP10 expression in primary lung adenocarcinoma using a public database, found that FKBP10 is also selectively expressed in primary lung adenocarcinoma, and affects the overall survival and disease-free survival of patients. LimitationsThe number of enrolled patients was relatively small and patients’ treatment options varied. ConclusionsA combination of surgical resection, adjuvant radiotherapy, and precise target therapy may benefit the survival of selected patients with lung adenocarcinoma brain metastases. FKBP10 is a novel biomarker for lung adenocarcinoma brain metastases, which is closely associated with survival time and may serve as a potential therapeutic target.

Increased NOTCH1 expression is associated with low survival in moderate/ poor differentiated human oral squamous cell carcinoma patients.

Notch deregulation has been reported in various types of cancers, including Oral squamous cell carcinomas (OSCCs). The role of Notch1 signaling in oral squamous cell carcinoma (OSCC) remains poorly understood. In this study, NOTCH1 was aberrantly expressed in human oral cancer tissues compared with that in normal marginal tissues and was associated with poor prognosis. The positive Notch 1 expression was significantly associated with poor tumor differentiation status. Kaplan-Meier survival curves revealed that elevated cytoplasmic NOTCH1 expression levels in OSCC patients were associated with poor overall survival. Moreover, multivariate COX proportional hazard models revealed that T N status, AJCC stage histological grade were independent prognostic factors for survival. Our result clearly demonstrates the oncogenic role of Notch1 in oral cancer and Notch1 may be a useful biomarker to target oral cancer patients.

The ALDH2, IGSF9, and PRDM16 Proteins as Predictive Biomarkers for Prognosis in Breast Cancer

IntroductionALDH2, IGSF9, and PRDM16 play crucial roles in regulating diverse cellular pathophysiologic functions. The current study was to evaluate the effect of the 3 proteins on clinicopathologic features and prognosis of patients with breast cancer. Materials and MethodsThe formalin-fixed and paraffin-embedded tissue specimens were collected from breast cancer patients by immunohistochemistry (IHC) were analyzed. ResultsOf the 216 patients enrolled, ALDH2 high expression was significantly correlated with the age (p = .040), larger tumor size (p = .001), LVI (p < .001), LNM (p < .001), advanced TNM staging (p < .001), PR (p = .027), HER2 status (p = .002), and molecular subtype (p = .003). IGSF9 low expression was significantly correlated with the LV1 (p = .024), LNM (p = .024), advanced TNM staging (p = .001). The low expression of PRDM16 was significantly correlated with age (p = .023), and LNM (p = .014). The A+I−P− expression (13.4%) were markedly correlated with lymphatic vessel invasion (LVI) (p < .001), lymph node metastasis (LNM) (p < .001), advanced TNM staging (p < .001). Furthermore, patients with A+I−P− expression had significantly advanced-stage breast cancer [stage III (72.4%) vs. (23.0%)]. Univariate and multivariate analysis identified variables (ie, larger tumor size, lymph node involvement, and A+I−P− expression) as independent prognostic factors for survival. ConclusionOur results reveal ALDH2 high expression, IGSF9 and PRDM16 low expression, A+I−P− expression was associated with advanced clinicopathological characteristics, and shorter OS and DFS in breast cancer patients. The 3 proteins may be potential prognosis markers and therapeutic targets for breast cancer patients.

Computerized tomography-based first order tumor texture features in non-small cell lung carcinoma treated with concurrent chemoradiation: A simplistic and potential surrogate imaging marker for survival.

This study examines the role of tumor texture on computed tomography (CT) images as a complement to clinical prognostic factors in predicting survival in patients of non-small cell lung carcinoma (NSCLC) treated with radical chemo-radiation (CRT). A total of 93 patients with confirmed NSCLC treated with CRT accrued in a study approved by the institutional ethics committee were analyzed for CT-based radiomic features. Pretreatment CT images were used to contour the primary tumor and texture features were computed by the image filtration method to differentially highlight fine to coarse textures. Texture parameters included mean intensity, entropy, kurtosis, standard deviation, and mean positive pixel and skewness. Optimal threshold cut-off values of the above tumor texture features were analyzed. These features were explored as imaging biomarkers to predict survival using Kaplan-Meier and Cox proportional hazard model. Median follow-up of the entire cohort was 23.5 months [Interquartile range, IQR: 14-37] while for alive patients, median follow-up was 31 months (IQR: 23-49), 47 (50.6%) patients had died at the last follow-up. Univariate analysis revealed certain features like age, gender, response to therapy, and texture features like mean and kurtosis in CT images to be significant predictors of survival. In multivariate analysis, age (P = 0.006), gender (P = 0.004), treatment response (P< 0.0001), and two CT texture parameters: mean (P = 0.027) and kurtosis (P= 0.002) were independent prognostic factors of survival. CT-derived tumor heterogeneity (mean and kurtosis) complements clinical factors for predicting survival in NSCLC patients treated with CRT. Tumor radiomics warrants further validation as potential prognostic biomarkers for these patients.

Pre-Transplant Multiparameter Flow Cytometric Measurable Residual Disease in Acute Myeloid Leukemia As an Independent Prognostic Factor for Survival after Myeloablative Allogeneic Hematopoietic Cell Transplantation

Background Growing evidence suggests that multiparameter flow cytometric (MFC) measurable residual disease (MRD) assessment in acute myeloid leukemia (AML) should be used for risk stratification prior to allogeneic hematopoietic stem cell transplantation (alloHCT). We investigated the significance of MFC-MRD status in AML patients treated with myeloablative conditioning (MAC) alloHCT at transplant centers within the Polish Adult Leukemia Group (PALG). Methods All consecutive patients who underwent MAC alloHCT from HLA identical siblings (SD), family haploidentical donor, matched (10/10) unrelated donor (MUD), or mismatched (9/10) unrelated donor (mMUD) between January 2014 and May 2022 and for whom pre-transplant MFC-MRD was assessed were included in the analysis. MFC-MRD assessment has been routinely performed on bone marrow aspirates obtained before alloHCT since 2014 or as part of the PALG-AML1/2016 study protocol (NCT03257241) since 2018. Flow cytometry laboratory protocols were modified and unified by the cooperating laboratories according to the European LeukemiaNet recommendations in 2018. Residual disease at a level ≥0.1% was considered MRD(+). Results We analyzed 302 adult patients (median age 44 years, range 18-68) with AML in first (88%) or subsequent CR (12%) after intensive chemotherapy, including 81 patients (27%) transplanted between 2014-2017 and 221 (73%) transplanted between 2018-2022. Positive MRD status before alloHCT was detected in 143/302 pts (47%). The European LeukemiaNet (ELN) cytogenetic/genetic risk (Dohner 2010) was available in 290 of the 302 patients and was intermediate-II (Int-II)/high in 22%. Patients received MAC based on i.v. busulfan (84%), treosulfan (1%) or total body irradiation (15%) and graft from either SD (29%), haploidentical donor (9%), MUD (55%), or mMUD (7%). GvHD prophylaxis consisted of calcineurin inhibitor (CNI) combined with MTX (with or without ATG) or was based on post-transplant cyclophosphamide in transplants from haploidentical donor or mMUD. After the median follow-up of 30 months (range, 1-97), the 3-year LFS and OS for MRD(-) vs MRD(+) patients was 69% vs 54% (log-rank p=0.007), and 77% vs 62% (log-rank p=0.013), respectively. In multivariate Cox model, the independent adverse prognostic factors for LFS were MRD positive status (HR 1.53, 95%CI 1.03-2.25; p=0.0332), Int-II/high ELN risk (HR 1.87, 95%CI 1.24-2.84; p=0.0031), and age ≥ 45 years (HR 1.65, 95%CI 1.12-2.45; p=0.011). The same factors independently influenced OS [HR 1.59, 95%CI 1.01-2.48; p=0.0411; HR 1.67, 95%CI 1.03-2.71; p=0.0363, and HR 1.79, 95%CI 1.42-2.79; p=0.0109, respectively]. When the patients were classified according to the number of identified independent risk factors, the 3-year LFS and OS for patients with 0, 1, 2 and 3 risk factors was 75%, 68%, 51%, and 27% (p<0.0001) (Figure 1), and 81%, 77%, 57%, and 44%, respectively (p=0.0006). Conclusions Our findings confirm that pre-transplant residual disease at a ≥0.1% level assessed by MFC is an independent poor prognostic factor for both LFS and OS in AML patients treated with MAC alloHCT. As predicted, outcomes after MAC alloHCT were also independently influenced by ELN cytogenetic/genetic risk and age. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

PN3b as an independent risk factor for poor prognosis and peritoneal recurrence in Borrmann type IV gastric cancer: A retrospective cohort study

The clinicopathological features and surgical treatment strategies of Borrmann type IV gastric cancer (GC) remain controversial. Peritoneal metastasis is the most common recurrence pattern in patients with Borrmann type IV GC. Among 2026 gastric cancer between January 2009 and August 2019, 159 cases of Borrmann type IV GC were included in this study (7.8%). We retrospectively analyzed the clinicopathological characteristics and prognosis of these patients. Univariate and multivariate Cox proportional hazards were applied to identify independent prognostic factors. Predictors related to peritoneal metastasis of type IV GC were analyzed by multivariate Cox regression analysis. Borrmann type IV gastric cancer was associated with more advanced clinicopathological features at diagnosis than the other Borrmann type GC. Of the 159 patients with Borrmann type IV GC, the median OS was 23 months. The number of patients with peritoneal metastasis was 43, accounted for 27.0% of all the patients and 87.8% of the patients with distant metastasis. Multivariate analyses revealed lymph node metastasis to be independent prognostic factor for survival in Borrmann type IV GC patients. pN3b and tumor size > 50 mm showed to be risk factors for peritoneal metastasis. Borrmann type IV GC is an important independent prognostic factor. pN3b is an independent prognostic factor and a predictor of peritoneal metastasis in patients with Borrmann type IV GC.

Construction and validation of an immune-related genes prognostic index (IRGPI) model in colon cancer.

Though immunotherapy has become one of the standard therapies for colon cancer, the overall effective rate of immunotherapy is very low. Constructing an immune-related genes prognostic index (IRGPI) model may help to predict the response to immunotherapy and clinical outcomes. Differentially expressed immune-related genes (DEIRGs) between normal tissues and colon cancer tissues were identified and used to construct the co-expression network. Genes in the module with the most significant differences were further analyzed. Independent prognostic immune-related genes (IRGs) were identified by univariate and multivariate cox regression analysis. Independent prognostic IRGs were used to construct the IRGPI model using the multivariate cox proportional hazards regression model, and the IRGPI model was validated by independent dataset. ROC curves were plotted and AUCs were calculated to estimate the predictive power of the IRGPI model to prognosis. Gene set enrichment analysis (GSEA) was performed to screen the enriched KEGG pathways in the high-risk and low-risk phenotype. Correlations between IRGPI and clinical characteristic, immune checkpoint expression, TMB, immune cell infiltration, immune function, immune dysfunction, immune exclusion, immune subtype were analyzed. Totally 680 DEIRGs were identified. Three independent IRGs,NR5A2, PPARGC1A and LGALS4, were independently related to survival. NR5A2, PPARGC1A and LGALS4 were used to establish the IRGPI model. Survival analysis showed that patients with high-risk showed worse survival than patients in the low-risk group. The AUC of the IRGPI model for 1-year, 3-year and 5-year were 0.584, 0.608 and 0.697, respectively. Univariate analysis and multivariate cox regression analysis indicated that IRGPI were independent prognostic factors for survival. Stratified survival analysis showed that patients with IRGPI low-risk and low TMB had the best survival, which suggested that combination of TMB and IRGPI can better predict clinical outcome. Immune cell infiltration, immune function, immune checkpoint expression and immune exclusion were different between IRGPI high-risk and low-risk patients. An immune-related genes prognostic index (IRGPI) was constructed and validated in the current study and the IRGPI maybe a potential biomarker for evaluating response to immunotherapy and clinical outcome for colon cancer patients.

A pyroptosis-related gene model and its correlation with the microenvironment of lung adenocarcinoma: A bioinformatics analysis and experimental verification.

Background: Non-small cell lung cancer, comprising lung adenocarcinoma (LUAD) and lung squamous cell carcinoma, is one of the leading causes of cancer-related mortality. Pyroptosis is a new form of programmed cell death involved in cancer development. The relationship between LUAD and pyroptosis is unclear. This research aims to investigate this relationship and develop a stratified clinical model based on pyroptosis-related genes (PRGs). Methods: We analyzed the data of LUAD from The Cancer Genome Atlas (TCGA) and evaluated the expression of 48 PRGs to identify the differentially expressed genes. Then, constructing the risk model using the least absolute shrinkage and selection operator and the Cox regression method to find the gene signatures. The functional enrichment, immune cell infiltration, tumor mutational burden (TMB), and expression of immune checkpoints were compared to investigate the potential mechanism. The IC50 of common drugs was evaluated and compared. The inflammasome activation assay and lactate dehydrogenase (LDH) assay of NLR-family CARD-containing protein 4 (NLRC4) were also performed to confirm the role of pyroptosis in LUAD. Results: The pyroptosis-related model accurately predicted the prognosis of patients with LUAD, with the low-risk group exhibiting a higher survival probability. The risk score was an independent prognostic factor for survival. The stratified patients exhibited distinct tumor microenvironments, TMB, and drug sensitivity. The validation experiments of NLRC4 confirmed its role in inducing pyroptosis via promoting IL-1 maturation. Conclusion: PRGs regulated the tumor microenvironment and influenced the outcome of LUAD. NLRC4 may function as a hub gene in the process of LUAD.

Carotid space involvement is a prognostic factor and marker for induction chemotherapy in patients with nasopharyngeal carcinoma

ObjectivesThe carotid space is an integral part of the parapharyngeal space, with ambiguous prognostic value for patients with nasopharyngeal carcinoma (NPC). This study aimed to investigate the prognostic significance of carotid space involvement (CSI) and propose a treatment strategy. Materials and methodsThis retrospective study enrolled 792 patients with biopsy-confirmed, non-distant metastatic NPC staged by magnetic resonance imaging before treatment. We used multivariable Cox regression models and Kaplan–Meier methods to assess the association between the variables and survival outcomes. A matched-pair method (1:1) was used to compare the survival differences between the patients with CSI treated with induction chemotherapy (ICT)and that of those who were not. ResultsThe incidence rate of CSI was 21.7 % (172/792). Multivariate analysis revealed that CSI was not an independent prognostic factor for survival outcomes in the 792 patients with NPC; however, the Chi-square test showed a different distribution of treatment strategies with ICT for patients with and without CSI. After stratification by ICT, CSI was an independent prognostic factor for overall survival (OS) (p = 0.049) in patients without ICT, but not for distant metastasis-free, local recurrence-free, or progression-free survival (p˃0.05). Additionally, ICT improved OS in patients with CSI (hazard ratio, 0.42; p = 0.019). Matched pair analysis showed that patients with CSI gained prolonged OS from ICT compared with the non-ICT group (88.4 % vs 69.4 %, p = 0.028). ConclusionCSI was an independent negative prognostic factor for OS in patients with NPC without ICT and might be an imaging marker for identifying eligible candidates for ICT.