Prognostic Factor For OS Research Articles

Clinical Outcomes and Prognostic Factors in Patients With Penile Carcinoma: A Sub-Analysis From Meet-URO 23 (I-RARE) Registry Study

IntroductionPenile squamous cell carcinoma (PSCC) is a rare tumor with an aggressive behavior. The Meet-URO 23/I-RARE registry includes rare genitourinary malignancies. We extracted patients with PSCC to conduct a retrospective study aimed at assessing clinical outcomes and prognostic factors. Patients and MethodsPrimary endpoints were overall survival and progression-free survival. Prognostic factors for OS and PFS were analyzed using univariate and multivariate analysis.From the Meet-URO 23/I-RARE database, we extracted 128 patients with diagnosis of PSCC. About 48% of patients underwent first-line of therapy. ResultsIn the overall population, median OS from diagnosis was 34.6 months. Significant differences in median OS were observed according to ECOG PS at diagnosis (57.3 months vs. 8.3 months; P < .001), and median age (≤77y 88.8 months vs. >77y 26 months; P = .013). At multivariate analysis, ECOG PS 2-4 at diagnosis (HR 3.04) and lymph node metastases (HR 2.49) were independently associated with a higher risk of death.Among patients undergoing first-line therapy (n = 61), median OS was 12.3 months, and a statistically significant difference was found according to type of response to first-line (DCR 24.4 months vs. PD 7.1 months; P < .001). Multivariate analysis showed that only age >77 years was associated with a worse OS (HR 2.16). A statistically significant difference in PFS was found according to platinum plus 5-fluorouracil versus platinum plus taxane (4.9 vs. 3.4 months; P = .036) and regimens with 2 versus 3 drugs (3.4 vs. 8.6 months; P = .019). At the multivariate analysis only regimens with platinum plus taxane were associated with worse PFS (HR 2.83). ConclusionIn our registry study, PSCC is confirmed to be an aggressive disease. Poor ECOG PS, presence of lymph node metastases, and higher age at diagnosis appear to be associated with worse survival outcomes.

10210-STMO-13 CLINICAL AND GENETIC ANALYSIS OF ADULT THALAMIC GLIOMAS - SIGNIFICANCE OF H3K27M AND TERT MUTATIONS

Abstract Adult thalamic glioma (ATG) is a rare but deep lesion that is difficult to remove and often refractory to treatment. The diffuse midline glioma (DMG), H3K27M-mutant, newly introduced in the WHO 2016 classification, constitutes part of ATG, but the significance of H3K27M mutations in adult ATG and the prognosis of thalamic DMG are variable and inconsistent among reports. We retrospectively analyzed clinical, pathological, and molecular characteristics of 45 consecutive ATG cases operated on at our institution from 2007 to 2022, and examined outcomes and prognostic factors. The median age was 45 years (range, 18-74), median preoperative KPS was 70% (range, 40-100), median maximum tumor diameter on MRI was 37 mm (range, 22.6-62.6), Gd contrast was present in 31, and bilateral disease was present in 8 patients. 31 patients underwent resection and 14 underwent biopsy. Differences in the surgical approach did not affect OS. WHO G2: 2, G3: 7, and G4: 36, and all IDH wild-type. The mPFS for all patients was 9.5 months and mOS was 26.0 months; G4 consisted of 19 DMG and 17 GBM with mOS of 30.4 months DMG vs. 12.4 months GBM (P=0.012). Analysis of all cases showed a trend toward better prognosis for H3K27M mutation cases (P=0.118), while TERT was significantly worse for the mutation type with 29.2 months for wild type vs. 9.3 months for the mutation type (P=0.026). In univariate analysis, age and TERT mutation status were prognostic factors for OS, and in multivariate analysis, WHO grade was a prognostic factor for OS in addition to these factors. In the past literature of pediatric cases, H3K27M mutation was often reported as a prognostic factor, but in the present study, TERT mutation was the prognostic factor, suggesting that the significance of H3 mutation in thalamic gliomas in adults and children is different.

Lenvatinib Plus PD-1 Inhibitors versus Regorafenib in Patients with Advanced Hepatocellular Carcinoma After the Failure of Sorafenib: A Retrospective Study.

To evaluate the clinical outcomes of lenvatinib plus PD-1 inhibitors (LP) and regorafenib (R) in patients with advanced hepatocellular carcinoma (HCC) after sorafenib failure. From June 2018 to September 2021, 68 patients from a single center who received lenvatinib combined with PD-1 inhibitors or regorafenib after sorafenib treatment failure were analyzed. The tumor response and survival outcomes were compared between the LP group and R group. Prognostic factors for OS and PFS were determined using Cox proportional hazard regression models. The ORR increased in the LP group (19.5% vs 7.4%, p =0.294), and the DCR was better in the R group (73.2% vs 44.4%, p =0.017). Additionally, median PFS and OS were not significantly different between the LP group and R two groups in survival analysis (PFS: 5.3 months vs 3.0 months, p =0.633; OS: 11.8 months vs 8.0 months, p =0.699). The common adverse events (≥grade 3) were hand-foot skin reactions (13.1%). In multivariate analyses, AFP≥400 ng/mL and ECOG PS 2 were independent risk factors for poor prognosis. The LP group appeared to have a trend of greater tumor response and a higher disease control rate than the R group among patients with sorafenib-resistant HCC, although PFS and OS did not differ significantly between the two groups.

AHSG, a Gene Promoting Tumour Proliferation, Migration and Invasion, is an Independent Prognostic Factor for Poor Overall Survival in Lung Adenocarcinoma.

Recent studies have shown that the metabolic process-related gene AHSG is involved in multiple pathological processes of tumours. This study will explore the relationship between AHSG and lung adenocarcinoma. Expression analysis, survival analysis and co-expression analysis of AHSG were performed using a public database, and cytological and molecular biology assays were performed to explore the role of AHSG in lung adenocarcinoma. Compared with normal tissues, AHSG expression was significantly higher in cancer tissues in the TCGA-LUAD database, and pan-cancer analysis revealed abnormal AHSG expression in different kinds of tumours. Survival analysis revealed that compared with the low expression group, the patients in the high expression group had a significantly worse overall survival duration in the TCGA-LUAD database, and a subsequent study confirmed that AHSG expression could be an independent prognostic factor of overall survival in lung adenocarcinoma. AHSG-related genes are involved in multiple physiological and pathophysiological pathways. In subsequent cytological and molecular biology experiments, inhibition of AHSG expression suppressed proliferation, migration and invasion in lung adenocarcinoma cell lines, and the EMT process was blocked after knockdown of AHSG. AHSG could be used as a prognostic factor for OS in patients with lung adenocarcinoma. It can promote the biological behaviour of lung adenocarcinoma and may become a potential target for treatment, which is worthy of further study.

The prognostic role of lymphocyte to monocyte ratio (LMR) in patients with Myelodysplastic Neoplasms

ABSTRACTBackground:Previous studies validated the prognostic significance of lymphocyte to monocyte ratio (LMR) in patients with solid tumors and some hematologic malignancies. However, the correlation between LMR and Myelodysplastic Neoplasms (MDS) was unclear. The study intends to investigate the prognostic impact of LMR on MDS patients.Methods:91 newly diagnosed MDS patients were included in this retrospective study. The cut-off of LMR was 3.2 by X-Tile. All patients were divided into the low LMR group (<3.2) and the high LMR group (≥3.2). Clinical characteristics were compared between the two groups.Results:Patients in the high LMR group (n = 67) had better OS (P = 0.007) from the Kaplan-Meier survival curves. The results of the univariate analysis demonstrated that LMR was a prognostic factor for OS [hazard ratio (HR) = 2.070, 95%CI 1.201-3.571, P = 0.009]. After multivariate cox analysis, low LMR was confirmed to be an independent predictor of poor OS in MDS patients (HR = 1.872, 95%CI 1.084-3.230, P = 0.024).Conclusions:LMR, a representative marker of systematic inflammation and immune response, has potential prognostic significance in MDS patients.

Differential Expression and Clinical Relevance of C-X-C Motif Chemokine Receptor 4 (CXCR4) in Renal Cell Carcinomas, Benign Renal Tumors, and Metastases

C-X-C Motif Chemokine Receptor 4 (CXCR4) is part of the human chemokine system and involved in progression and metastasis in renal cell carcinoma (RCC). However, the role of CXCR4 protein expression in RCC remains controversial. In particular, data regarding the subcellular distribution of CXCR4 in RCC and RCC metastasis as well as CXCR4 expression in renal tumors of variant histology are limited. The aim of the present study was the evaluation of the differential CXCR4 expression in RCC primary tumor and metastatic tissue as well as in variant renal histologies. In addition, the prognostic capacity of CXCR4 expression in organ-confined clear cell RCC (ccRCC) was evaluated. Three independent renal tumor cohorts (primary ccRCC cohort n1 = 64; cohort of various histological entities n2 = 146; metastatic RCC tissue cohort n3 = 92) were evaluated using tissue microarrays (TMA). After immunohistochemical staining for CXCR4, nuclear and cytoplasmic expression patterns were evaluated. CXCR4 expression was correlated with validated pathologic prognosticators, clinical data, and overall and cancer-specific survival. Positive cytoplasmic staining was observed in 98% of the benign and 38.9% of the malignant samples. Nuclear staining was positive for 94.1% of the benign samples and 83% of the malignant samples. The median cytoplasmic expression score was found to be higher in benign tissue than in ccRCC (130.00 vs. 0.00); median nuclear expression score analysis indicated the opposite (56.0 vs. 71.0). Within malignant subtypes, the highest expression score was seen in papillary renal cell carcinomas (cytoplasmic: 117.50, nuclear: 41.50). Within benign renal tumors, high cytoplasmic and nuclear CXCR4 expression scores were seen for oncocytomas (cytoplasmic: 100.00, nuclear: 31.00). Expression scores in RCC metastasis ranked between benign renal tissue and ccRCC in cytoplasmic and nuclear expression. Cytoplasmic CXCR4 expression was identified as a prognostic factor for OS and CSS (p = 0.042; p = 0.019). Multivariate analysis including clinicopathological parameters did not reveal an independent prognostic character of CXCR4 expression. CXCR4 expression differs significantly within benign lesions and renal neoplasms. Cytoplasmic and nuclear expression of CXCR4 could be detected across all RCC subtypes. The prognostic value of CXCR4 in ccRCC was confirmed in univariate analysis.

KRAS WT pancreatic adenocarcinomas: Another disease?

750 Background: KRAS mutation is the most common molecular alteration (MA) in pancreatic adenocarcinoma (PDAC), and only 8-10% of patients (pts) harbor KRAS wild-type tumors (WT). This study describes clinical and molecular features of KRAS WT PDAC and compares it to mutant KRAS (m KRAS) PDAC. Methods: A retrospective chart review of clinical/molecular data was performed on all pts with PDAC who had contributive molecular profile at Gustave Roussy. KRAS status was determined on tumor molecular profiling as part of routine care using an in-house panel or Foundation Medicine NGS either on tissue (63%) or liquid biopsy (37%). Results: Overall, 41 pts with KRAS WT PDAC were compared to 197 pts with mKRAS PDAC. Median OS (mOS) from initial diagnosis was significantly higher in the KRAS WT group compared to mKRAS group (32.8 months (mts), CI95% [25.9-NR] vs 21.5 mts, CI95% [18.8-24.9] respectively), as mOS from metastatic diagnosis, 26 mts, CI95% [15.7-NR] for KRAS WT pts vs 17.7 mts CI95% [15.5-19.3] for mKRAS (all p&lt;0.05)). After adjustment on gender, age, metastasis status at diagnosis, hazard ratio (HR) of OS from metastatic stage diagnosis associated with KRAS status was 1.9 [1.1;3.4], p=0.02 (similar for 1st line PFS and OS from initial diagnosis). MA were found in 31 KRAS WT pts (76%). KRAS WT and m KRAS pts harbored different molecular profiles with less alterations of TP53, SMAD4 and CDKN2A/B (p&lt;0.05) in KRAS WT tumors, but more of BRAF (p&lt;0.05), PALB2, RET and BRIP1 (p=NS) alterations. Interestingly, 3 MSI tumors were found in the KRAS WT group (one received immunotherapy), vs none in m KRAS group). Tumor mutational burden was similar (2.00 Mut/Mb in KRAS WT pts vs 2.7 Mut/Mb in m KRAS pts). Based on ESCAT classification, a putative therapeutic target (ESCAT I-IV, other than KRAS) was identified in 15 (36%) KRAS WT pts and 65 (33%) m KRAS pts, thus enriching the therapeutic panel for these patients. Indeed, for example 9 (22%) KRAS WT pts received an oriented therapy after palliative treatments (such as anti-RET or anti-PARPs) and showed higher survival rates compared to KRAS WT pts who did not (mOS from diagnosis in months NR (14.2; NR) and 28.3 (26; NR) respectively). Conclusions: In our cohort of 238 PDAC, we confirm that KRAS is a prognostic factor of OS. KRAS WT PDAC have a significantly longer OS compared to m KRAS. Moreover, 36% of KRAS WT PDAC pts had a potentially actionable MA, and 9 pts displayed higher survival rates after receiving oriented therapies. This study suggests that KRAS WT PDAC should be eligible for a large molecular screening.[Table: see text]

Relationship between inflammatory indexes and Khorana score (KS) with prognosis and survival in pancreatic ductal adenocarcinoma (PDAC).

740 Background: Several inflammatory scores such as the Systemic Inflammation Response Index (SIRI), the Inflammation Index Score (IIS), and the Neutrophil Lymphocyte Ratio (NLR) have been reported to have prognostic value in PDAC with different results. We hypothesize that the KS, designed to predict the risk of cancer-associated thrombosis, may also be a surrogate marker for inflammation to be included as a relevant prognostic index for PDAC. Methods: Baseline characteristics and individual SIRI, IIS, NLR and KS indexes from 197 PDAC patients diagnosed in our center between 2019 and 2021 have been retrospectively recorded. PFS and OS (Log-rank test) have been used to compare the different scores of each index in the whole population as well as in the metastatic setting. Kruskal-Wallis test and Mann-Whitney test were also done to determine if the SIRI varies significantly between KRS values. Results: Of the 197 patients analyzed, 41 were resectable (20.8%), 54 locally advanced (27.4%) and 102 metastatic (51.8%). Patients with intermediate risk according to KS (2 points, n = 131, 66.5%) had a significantly higher median PFS (8.4 vs. 4.8 months, p = 0.03) and significantly higher OS (12.9 vs. 7.7 months, p = 0.002) than those with high-risk (&gt; 3 points, n = 66, 33.5%). The median OS for patients with low (&lt; 3,000) and high (&gt; 3,000) SIRI was 13.1 and 9.3 months respectively (p = 0.05). No significant differences were observed in PFS. In the metastatic setting, a low SIRI was significantly associated with higher OS (10.6 vs. 5.8, p = 0.016). No significant differences were observed in patients with low vs. high IIS and NLR. The Kruskal-Wallis test indicates that SIRI values vary between at least two KS values (p &lt; 0.001). The Mann-Whitney test found significant differences between the SIRI values from S 2 and 3 (p = 0.002) as well as 2 and 4 (p = 0.04). SIRI values were higher in patients with KRS &gt; 3 vs. 2. Conclusions: This retrospective analysis showed that patients with lower KS live longer and progress later than those with higher KS. Lower SIRI is associated with better survival in metastatic patients, being on the verge of statistical significance in the whole cohort. There is a strong correlation between SIRI and KS. In this cohort of unselected PDAC patients, KS is a prognostic factor for OS and PFS that correlates with subclinical inflammation and demonstrates to be a better predictor than other inflammatory indexes that deserves further analysis.

Image-guided adaptive brachytherapy for advanced cervical cancer spreading to the bladder and/or rectum: Clinical outcome and prognostic factors

IntroductionRefinements of brachytherapy techniques have led to better local control of locally advanced cervical cancer (LACC), especially with the development of image-guided adaptive brachytherapy (IGABT). Data on the efficacy of brachytherapy in cervical cancer spreading to adjacent organs are scarce. We report the experience of our institution in the treatment of these advanced tumors with IGABT. Materials and methodsMedical records of patients treated for a LACC spreading to the bladder and/or rectum between 2006 and 2020 at Gustave Roussy Institute were analyzed. Dosimetric parameters were collected and converted into 2 Gy per fraction equivalent doses, including the minimal dose received by 90% of the high-risk target volume (D90 CTVHR) and intermediate-risk target volume (D90 CTVIR), as well as the dose received by the most exposed 2 cm3 of the organs at risk. A Cox regression model was used to study the potential associations between clinical and dosimetric factors with survival endpoints and fistula formation. Results and statistical analysisA total of 81 patients were identified. All patients received pelvic+/− para-aortic radiotherapy, 45 Gy in 25 fractions +/− boost to gross lymph nodes. Concomitant platinum-based chemotherapy was administered in 93.8% of cases. The median D90 CTVHR dose was 75.5 GyEQD2 (SD: 10.39 GyEQD2) and median CTVHR volume was 47.6 cm3 (SD: 27.9 cm3). Median bladder and rectal D2cm3 dose were 75.04 GyEQD2 (SD: 8.72 GyEQD2) and 64.07 GyEQD2 (SD: 6.68 GyEQD2). After a median follow-up of 27.62 ± 25.10 months, recurrence was found in 34/81 patients (42%). Metastatic failure was the most common pattern of relapse (n = 25). Use of a combined interstitial/intracavitary technique and D90 CTVHR ≥ 75.1 GyEQD2 were prognostic factors for OS in univariate analysis (HR = 0.24, 95%IC: 0.057–1, p = 0.023; HR = 0.2, 95%IC: 0.059–0.68, p = 0.0025, respectively). In multivariate analysis, a D90 CTVHR ≥ 75.1 GyEQD2 was significant for OS (HR = 0.23; 95%IC: 0.07, 0.78, p = 0.018). The occurrence of vesicovaginal fistula (VVF) was the most frequent pattern of local recurrence (HR = 4.6, 95%CI: 1.5–14, p = 0.01). ConclusionAdvances in brachytherapy modalities improved local control and survival while reducing toxicities. Enhancing local control through dose escalation and combined intracavitary/interstitial brachytherapy techniques is a major factor in patients cure probability, together with systemic intensification to better control distant events.

Short- and long-term outcomes from the upfront high-dose chemotherapy, followed by autologous hematopoietic stem cell transplantation in diffuse large B-cell lymphoma

Introduction. Diffuse large B-cell lymphoma (DLBCL) is the most common (30-35%) type of B-cell lymphomas. Only about 60% of all newly diagnosed advanced-stage DLBCL can be completely treated by x6 CHOP-R only. High dose chemotherapy (HDCT) followed by autologous hematopoietic stem cell transplantation in the first remission (upfront auto-HSCT) can serve an option to improve prognosis in these patients (pts).Aim. To improve prognosis in DLBCL IV stage, IPI ≥2 pts by upfront auto-HSCT.Materials and methods. Included 105 pts: DLBCL NOS, age 18-65, stage IV, IPI ≥2, CR/PR after x6 CHOP/EPOCH + R from 2010 to 2019 at NMRC of Oncology named after N.N. Petrov of MoH of Russia were retrospectively analyzed. HSCT group includes pts with upfront HDCT followed by auto-HSCT (n = 35). The control group includes pts with non-invasive follow-up after induction only (n = 70). Primary endpoints were overall (OS) and progression-free survival (PFS). Secondary endpoints were response rate, relapse rate and treatment toxicity.Results and discussion. The 3-yr OS (p = 0.01) and 3-yr PFS (p = 0.018) were significantly higher in HSCT group. The complete response rate was significantly increased after upfront auto-HSCT (p &lt; 0.001). Early relapse served as an independent negative prognostic factor in OS (p &lt; 0.001) and experienced statistically less in HDCT group (p = 0.027). Early (ER) and late relapse (LR) rate were higher in pts with DEL (ER - p &lt; 0.001, LR - p &lt; 0.001 in control group and ER - p &lt; 0.001, LR -p = 0.013 in all pts). The overall relapse rate was higher if pts had &gt;1 extranodal site with lung involvement (p &lt; 0.004 in the control group and p = 0.021 in all pts). Prognostic models suggested DEL and presence of &gt;1 extranodal site with lung involvement as an independent negative prognostic factors for increasing the relapse probability in two years after treatment.Conclusion. Upfront HSCT can serve as a clinical option to consolidate the first remission in IV stage DLBCL pts with DEL and/or &gt;1 extranodal sites with lung involvement.

Lymphocyte to monocyte ratio in metastatic pancreatic ductal adenocarcinoma as a prognostic factor and its potential role in identifying a subset of patients with a favorable response to therapy.

4153 Background: Despite the most recent therapeutic achievements, pancreatic ductal adenocarcinoma (PDAC) is characterized by poor prognosis and response to treatments. Among the most investigated prognostic biomarkers, the lymphocyte to monocyte ratio (LMr) is gaining increasing interest in literature, mostly in hematological malignancies, breast cancer, bladder cancer, non-small cell lung cancer, colorectal cancer, and resected pancreatic adenocarcinoma. In these settings, a higher LMr allows identifying a subset of patients with a better prognosis. Our study aimed to evaluate the role of the LMr as a prognostic factor in patients affected by metastatic PDAC and to find a cut-off value able to identify a subset of patients with better prognosis and possibly susceptible to other therapeutic options. Methods: Data from 228 patients were collected retrospectively from 2014 to 2021. 175 from the Department of Medical Oncology of the University Hospital of Cagliari and 53 from the Oncology Clinic - University Hospital of Ospedali Riuniti of Ancona. All patients had metastatic PDAC and blood samples were collected before starting first-line chemotherapy. The cut-off value for LMr was calculated according to the ROC curves at 6, 12, and 18 months. Kaplan-Meier curves were then obtained for the evaluation of survivals. Finally, multivariate analysis was performed, taking into consideration the following prognostic factors: sex, ECOG-PS, NL ratio, metastatic sites, Ca19.9 and LDH. Results: The median age was 68 y.o. (range 39-84 y.o.), 123 (54%) were males. Cut off value obtained for LMR, was 4. 156 (68,4%) patients had an LMr &lt; 4 and 72 (31,6%) patients had an LMR ≥ 4. Patients with a ratio ≥ 4 showed a statistically significant difference in terms of median overall survival compared to patients with a ratio &lt; 4 (23 months versus 11 months, p &lt; 0.0001). First-line median progression-free survival was also different in patients with a value greater than or equal to 4 (11 months versus 6 months, p = 0.005), suggesting a better treatment response in the first group of patients. Finally, multivariate analysis showed that LMR ≥ 4 is an independent prognostic factor for OS ( p = 0.0005). Conclusions: The results of our study show that the lymphocyte to monocyte ratio could be an important prognostic factor in patients with metastatic pancreatic ductal adenocarcinoma, although the limitations of a retrospective study should be considered. Furthermore, these findings suggest the active role of the immune response in limiting disease progression, indicating a group of patients who could benefit most from a target or combined immunotherapy treatment.

Prognostic value of lipid metabolism-related genes and serum ApoA1 in patients with NSCLC.

e21040 Background: Altered lipid metabolism exhibited by cancer cells, this study was conducted to explore the prognostic values of lipid metabolism-related genes and serum lipids for survival in non-small-cell lung cancer (NSCLC) patients. Methods: Differential expression of the lipid metabolism-related genes CD36, LDLR, ACLY, ACSS2, FASN, SCD, HMGCR, and SQLE in cancer tissues were conducted by tumor immune estimation resource (TIMER) analysis. The gene expression profiling interactive analysis (GEPIA) tool was used to confirm the differential gene expression levels of lipid metabolism-related genes in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). Using a Kaplan-Meier plotter (K-M plotter), the prognostic value of lipid metabolism-related genes was assessed for LUAD and LUSC, including the hazard ratio (HR), 95% confidence interval (CI), and log-rank P-value. In addition, a retrospective study was conducted on patients with stage IV NSCLC diagnosed in Hubei Cancer Hospital. The optimal cutoff values for serum lipids were determined by X-Tile software. The chi-squared and Fisher’s exact probability tests were used to analyze count data. Survival curves were analyzed using the Kaplan-Meier, and the survival differences were assessed for statistical significance using the log-rank test. The Cox regression model was used to analyze the prognosis value of serum lipids. Data were analyzed using the SPSS 25.0 software, and P &lt; 0.05 was considered statistically significant. Results: TIMER dataset showed that expressions of CD36, LDLR, ACSS2, FASN and SCD were relatively low in both LUAD and LUSC, whereas ACLY exhibited significantly elevated expression. The GEPIA tool identified CD36 and ACSS2 as having downregulated expression in both LUAD and LUSC. The results also indicated that LDLR expression was relatively low in LUAD. Interestingly, we observed that high expression of CD36 had positive impacted on OS in LUAD (P = 0.01, HR = 0.66 (0.49 – 0.91)), while a negative impact in LUSC was exhibited (P = 0.01, HR = 1.43 (1.09 – 1.87)). The results also confirmed the prognostic values of LDLR (LUAD: P = 0.05, HR = 1.34 (0.99 – 1.8); LUSC: P = 0.03, HR = 1.35 (1.03 – 1.77) and ASCC2 (LUAD: P = 0.04, HR = 0.73 (0.53 – 0.99); LUSC: P = 0.05, HR = 0.76 (0.58 – 0.99). According to the results of chi-square test and Fisher’s exact test, ApoA1 was significantly related to gender (P &lt; 0.01), smoking status (P = 0.02), drinking status (P = 0.04), CHOL (P &lt; 0.001), TG (P &lt; 0.01), HDL-C (P &lt; 0.001) and LP(a) (P &lt; 0.001). High ApoA1 was associated with poor OS (ApoA1: 25.2 vs 31.2 months, P = 0.02) in univariate analysis. Multivariate Cox Regression model confirmed that ApoA1 was an independent prognostic factors for OS (P = 0.03, HR = 1.74, 95% CI: 1.07–2.83). Conclusions: These findings suggest that lipid metabolism-related genes and serum lipids can be used as prognostic biomarkers for determining prognosis in NSCLC.

Mutational landscape of chronic myelomonocytic leukemia in Chinese patients

BackgroundChronic myelomonocytic leukemia (CMML) is a rare and heterogeneous hematological malignancy. It has been shown that the molecular abnormalities such as ASXL1, TET2, SETBP1, and SRSF2 mutations are common in Caucasian population.MethodsWe retrospectively analyzed 178 Chinese CMML patients. The targeted next generation sequencing (NGS) was used to evaluate 114 gene variations, and the prognostic factors for OS were determined by COX regression analysis.ResultsThe CMML patients showed a unique mutational spectrum, including TET2 (36.5%), NRAS (31.5%), ASXL1 (28.7%), SRSF2 (24.7%), and RUNX1 (21.9%). Of the 102 patients with clonal analysis, the ancestral events preferentially occurred in TET2 (18.5%), splicing factors (16.5%), RAS (14.0%), and ASXL1 (7.8%), and the subclonal genes were mainly ASXL1, TET2, and RAS. In addition, the secondary acute myeloid leukemia (sAML) transformed from CMML often had mutations in DNMT3A, ETV6, FLT3, and NPM1, while the primary AML (pAML) demonstrated more mutations in CEBPA, DNMT3A, FLT3, IDH1/2, NPM1, and WT1. It was of note that a series of clones were emerged during the progression from CMML to AML, including DNMT3A, FLT3, and NPM1. By univariate analysis, ASXL1 mutation, intermediate- and high-risk cytogenetic abnormality, CMML-specific prognostic scoring system (CPSS) stratifications (intermediate-2 and high group), and treatment options (best supportive care) predicted for worse OS. Multivariate analysis revealed a similar outcome.ConclusionsThe common mutations in Chinese CMML patients included epigenetic modifiers (TET2 and ASXL1), signaling transduction pathway components (NRAS), and splicing factor (SRSF2). The CMML patients with DNMT3A, ETV6, FLT3, and NPM1 mutations tended to progress to sAML. ASXL1 mutation and therapeutic modalities were independent prognostic factors for CMML.

Ringed fluorodeoxyglucose uptake predicted poor prognosis after resection of pulmonary pleomorphic carcinoma

BackgroundPulmonary pleomorphic carcinoma (PPC) is a relatively rare and poorly differentiated non-small cell carcinoma. This study aimed to investigate the clinicopathological features including programmed cell death ligand 1 (PD-L1) expression status in patients with PPC who underwent curative resection.MethodsWe retrospectively studied 29 consecutive patients who had undergone anatomical lung resections for PPC. Perioperative and pathological variables, including radiological findings, were investigated to define prognostic factors.ResultsOverall survival (OS) rates were 71.8% at 1 year and 60.0% at 5 years. Disease-free survival (DFS) rates were 54.8% at 1 year and 43.6% at 5 years. Univariate analysis revealed that ringed fluorodeoxyglucose (FDG) uptake on positron emission tomography/computed tomography (PET/CT) (p = 0.003), a cavity in the tumor on CT (p = 0.004), and tumor size (> 40 mm) (p = 0.014) were poor prognostic factors for OS. Regarding DFS, ringed FDG uptake (p = 0.002), a cavity on CT (p < 0.001), tumor size (p = 0.007), and pleural invasion (p = 0.014) were poor prognostic factors. PD-L1 expression was not a prognostic factor.ConclusionThis study showed for the first time that ringed FDG uptake on PET/CT is a poor prognostic factor of PPC. PD-L1 expression status was not related to the prognosis.Trial registration The study was approved by the Kobe City Medical Center General Hospital’s ethics board (No. 20112) on August 20, 2020.

Preoperative Muscle-Adipose Index: A New Prognostic Factor for Gastric Cancer.

Studies have shown that traditional nutrition indicators and body composition indicators are closely related to prognosis after radical gastric cancer (GC) surgery. However, the effect of the combined muscle and adipose composite on the prognosis of GC has not been reported. The clinicopathological data of 514 patients with GC were retrospectively analyzed. The skeletal muscle adipose tissue were measured by preoperative CT images to obtain the muscle index and adipose index. X-tile software was used to determine the diagnostic threshold of muscle-adipose imbalance. The 5-year OS and RFS of the muscle-adipose imbalanced group were significantly worse than those of the balanced group. Multivariate analysis showed that muscle-adipose imbalance and the CONUT score were independent prognostic factors of OS and RFS (p < 0.05). The nuclear density curve showed that the recurrence risk of the muscle-adipose imbalanced group was higher than that of the balanced group, whereas the nuclear density curve of the CONUT score was confounded. Incorporating the muscle-adipose index into cTNM has the same prognostic performance as the pTNM staging system. Chemotherapy-benefit analysis showed that stage II/III patients in the muscle-adipose balanced group could benefit from adjuvant chemotherapy. The preoperative muscle-adipose index discovered for the first time is a new independent prognostic factor that affects the prognosis with GC. In addition, the preoperative muscle-adipose index is better than traditional nutrition and body composition indicators in terms of the prognostic evaluation of GC patients and the predictive value of recurrence risk.

Identification of a Novel Glycosyltransferase Prognostic Signature in Hepatocellular Carcinoma Based on LASSO Algorithm.

Although many prognostic models have been developed to help determine personalized prognoses and treatments, the predictive efficiency of these prognostic models in hepatocellular carcinoma (HCC), which is a highly heterogeneous malignancy, is less than ideal. Recently, aberrant glycosylation has been demonstrated to universally participate in tumour initiation and progression, suggesting that dysregulation of glycosyltransferases can serve as novel cancer biomarkers. In this study, a total of 568 RNA-sequencing datasets of HCC from the TCGA database and ICGC database were analysed and integrated via bioinformatic methods. LASSO regression analysis was applied to construct a prognostic signature. Kaplan–Meier survival, ROC curve, nomogram, and univariate and multivariate Cox regression analyses were performed to assess the predictive efficiency of the prognostic signature. GSEA and the “CIBERSORT” R package were utilized to further discover the potential biological mechanism of the prognostic signature. Meanwhile, the differential expression of the prognostic signature was verified by western blot, qRT–PCR and immunohistochemical staining derived from the HPA. Ultimately, we constructed a prognostic signature in HCC based on a combination of six glycosyltransferases, whose prognostic value was evaluated and validated successfully in the testing cohort and the validation cohort. The prognostic signature was identified as an independent unfavourable prognostic factor for OS, and a nomogram including the risk score was established and showed the good performance in predicting OS. Further analysis of the underlying mechanism revealed that the prognostic signature may be potentially associated with metabolic disorders and tumour-infiltrating immune cells.

A classification based on tumor-stroma ratio and tumor budding for patients with muscle-invasive bladder cancer

Background Tumor-stroma ratio (TSR) and tumor budding (TB) play important roles in muscle-invasive bladder cancer (MIBC). We developed a rating system (TSR-TB type) based on the morphological evaluation of TSR and TB for predicting patient outcome and using individualized care. Research design and methods TSR and TB were assessed in publicly accessible MIBC tumor slides from the TCGA database. MIBC patients were classified as low stromal type or high stromal type based on TSR, and high stromal type was further classified as compartmentalized stromal type or mixed stromal type based on TB. Results TSR-TB type was an independent adverse prognostic factor for OS in MIBC (P<0.001). Low stromal type had a greater prognosis than the other subtypes (P<0.001) and were enriched for FGFR3 mutations (P=0.001), which could be susceptible to targeted therapy. The mixed stromal type was distinguished by increased M2 macrophage penetration (P<0.001), anti-tumor immune activity, DNA repair pathway mutations, and poor survival. GSEA showed that certain cancer-related pathways, such as mitotic spindle, PI3K-AKT-MTOR signaling, and the G2M checkpoint, were hyperactivated in high stromal type (all FDR<0.05). Furthermore, mixed stromal type demonstrated enhanced activation of epithelial mesenchymal transformation (EMT), inflammatory response, KRAS signaling, and angiogenesis (all FDR<0.05). Conclusion TSR and TB-based MIBC classification coincides with patient survival and molecular alterations. The identified subtypes may have important implications for individualized MIBC therapy.

Decreased serum apolipoprotein A1 level predicts poor prognosis of patients with de novo myelodysplastic syndromes

BackgroundMyelodysplastic syndromes (MDS) is a group of heterogeneous myeloid clonal diseases originating from hematopoietic stem cells. It has been demonstrated that apolipoproteins A1(ApoA1) are associated with disease risk in many cancer types. However, there still lacks evidence regarding the link between ApoA1 and MDS. This study was designed to investigate the prognostic value of pretreatment ApoA1 levels in MDS patients.MethodsWe retrospectively analyzed a cohort of 228 MDS patients to explore the prognostic value of the serum ApoA1 levels at diagnosis. Patients were divided into the high ApoA1 group and the low ApoA1 group. The prognostic significance was determined by univariate and multivariate Cox hazard models.ResultsMDS patients with low ApoA1 levels had significantly shorter overall survival (OS, P < 0.0001) along with a higher frequency of TP53 mutation (P = 0.002). Based on univariate analysis, age (≥ 60 years), gender (male), lower levels of hemoglobin (< 10 g/dl), HDL (≤0.91 mmol/L), higher bone marrow blast percentage (> 5%), higher IPSS-R scores and poorer karyotype were significantly associated with decreased OS. However, low ApoA1 level did not influence leukemia-free survival (LFS, P = 0.367). Multivariate Cox proportional hazards regression analysis indicated that low ApoA1 level (≤ 1.02 g/L) was also an independent adverse prognostic factor for OS in MDS (P = 0.034).ConclusionsDecreased ApoA1 level predicts a poor prognosis of MDS patients and thus provides a novel evaluation factor for them that is independent of the IPSS-R system.

Predictive value of preoperative platelet-to-albumin ratio and apolipoprotein B-to-apolipoprotein A1 ratio for osteosarcoma in children and adolescents: a retrospective study of 118 cases

BackgroundThis retrospective study investigated biomarkers that can reflect coagulation, inflammation, and lipid abnormalities: platelet-to-albumin ratio (PAR), platelet-to lymphocyte ratio (PLR), low-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (LDL-C/HDL-C), apolipoprotein B-to-apolipoprotein ratio (ApoB/ApoA1) whether may be viable prognostic predictors in children and adolescents with osteosarcoma.MethodsThe retrospective review has enrolled a total of 118 children and adolescent patients diagnosed with osteosarcoma. Analyses with a receiver operating characteristic (ROC) curve were performed to evaluate the optimal cut-off values and to compare the area under curves (AUC). Kaplan–Meier curves were used to visualize survival outcome and a Cox proportional hazards model were used to confirm independent prognostic factors.ResultsOsteosarcoma patients in high PAR group (> 4.41) and high ApoB/ApoA1 group (> 0.82) experienced significantly shorter overall survival compared with those in low PAR group (≤ 4.41) and low ApoB/ApoA1 group (≤ 0.82). In univariate and multivariable analyses, preoperative PAR and ApoB/ApoA1 were identified as independent prognostic factors for OS in children and adolescents with osteosarcoma.ConclusionPreoperative PAR and ApoB/ApoA1 can be used as promising predictors in children and adolescents with osteosarcoma to help clinicians recognize patients with an increased risk of poor prognosis.

Impact of hydronephrosis and kidney function on survival in newly diagnosed advanced cervical cancer

ObjectivesTo assess the impact of hydronephrosis and kidney function in newly diagnosed advanced cervical cancer patients. MethodsA retrospective cohort study of newly diagnosed cervical cancer stage IIIB to IVB was conducted in a tertiary hospital in Brazil. Data from clinical records between 2014 and 2018 were reviewed. ResultsA total of 285 women with advanced cervical cancer and no previous cancer treatment were included. 108 (37.9%) patients were diagnosed with hydronephrosis (HN) before or during the first treatment, 49 (17.2%) patients underwent ureteral obstruction relief, and emergency hemodialysis was performed in 17 patients due to uremia. The median overall survival (mOS) was 46.9 months for non-HN, 19.2 months for unilateral-HN, and 10.0 months for bilateral-HN (non-HN vs HN-groups, p = 0.0001). Patients with eGFR >= 60 mL/min/1.73 m2, before or during the first cancer treatment, had mOS of 46.9 months, 23.5 months, and 11.1 months for non-HN, unilateral-HN and bilateral-HN, respectively (non-HN vs bilateral-HN, p = 0.002). Patients with eGFR < 60 mL/min/1.73 m2 had mOS 23.4 months, 19.2 months, and 10.0 months for non-HN, unilateral-HN and bilateral-HN, respectively (non-HN vs bilateral-HN, p = 0.003). In the HN group, mOS was 11.2 months among those who underwent urinary diversion and 15.6 months among those who did not; p = 0.2. On multivariate analysis, cancer treatment, FIGO stage, and HN were prognostic factors for OS; however eGFR < 60 mL/min/1.73 m2 does not appear to be associated with worse survival by itself (p = 0.7). ConclusionHN seems to have a negative effect on survival of patients with cervical cancer even after adjustment for FIGO stage and cancer treatment. The mOS does not appear to be worse in patients with HN who required urinary diversion compared to those who did not.