Poor Prognostic Factor In Patients Research Articles

Recurrence-free survival curve for pulmonary metastasectomy in colorectal cancer plateaus at 3years.

Pulmonary metastasectomy in colorectal cancer (CRC) has encouraging results; however, specific criteria for lung resection and the timing of resection remain undetermined. Therefore, in this study, we aimed to examine the long-term prognosis and 10-year survival rates and analyze poor prognostic factors in patients who underwent resection of pulmonary metastases from CRC. This retrospective, single-institution study included 156 patients with controlled primary CRC and metastases confined to the lungs or liver who underwent pulmonary metastasectomy between 2005 and 2022. Statistical analyses were conducted using the X2 and two-tailed Student's t test to compare variables. The receiver operating characteristic (ROC) curve was used to determine the appropriate cut-off point for tumor size as a predictive factor of survival. Recurrence-free survival (RFS) and overall survival (OS) were estimated using the Kaplan-Meier method, and non-parametric group comparisons were performed using log-rank tests. The 5- and 10-year OS rates were 67% and 59%, respectively. Further, there was no recurrence 38months post-surgery, and the RFS curve plateaued. Moreover, by 88months post-surgery, no deaths occurred, and the OS curve plateaued. Multivariate analysis revealed that a pulmonary metastatic tumor >14mm and disease-free interval <2years indicated poor prognosis. The RFS curve for pulmonary metastasectomy may plateau approximately 3years after surgery. Pulmonary metastasectomy can achieve long-term survival in selected patients with CRC. Furthermore, surgical resection of recurrence after pulmonary metastasectomy may lead to better results. Thus, tumor size and disease-free interval may be independent prognostic factors.

Association between anti-Topoisomerase I antibody and organ damage in systemic sclerosis at the National Hospital of Dermatology and Venereology

Objectives: To evaluate the association between anti-Topoisomerase (Topo) I antibody and damage of some organs in systemic sclerosis (SSc). Materials and methods: Cross-sectional descriptive study of 100 patients diagnosed with SSc and were tested for anti-Topo I antibodies by ELISA technique at the National Hospital of Dermatology and Venereology. Results: The average score of general effects, thickened skin lesions, peripheral vascular damages, and lung damages according to the Medsger scale of the group of SSc patients with positive anti-Topo I was higher than SSc patients with negative anti-Topo I (0.93±1.07 vs 0.24±0.44; 1.6±0.7 vs 1.16±0.37; 1.88±0.61 vs 1.36±0.49, and 1.23±0.67 vs 0.84±0.94, respectively). The proportion of patients with joint contractures in the positive anti-Topo I group was higher than in the anti-Topo I negative group (32 vs 12%). The proportion of patients with severe and very severe organ damage in the anti-Topo I positive group was higher than in the anti-Topo negative group. There was no association between the presence of anti-Topo I and heart or digestive damage. Conclusions: Anti-Topo I antibodies were associated with the level of general effects, peripheral vascular damage, skin thickening, and pulmonary fibrosis. The presence of anti-Topo I antibodies would be a poor prognostic factor for patients with SSc.

Global research trends in immunotherapy for non-small cell lung cancer patients with KRAS mutations: a bibliometric analysis

BackgroundImmunotherapy, frequently combined with conventional chemotherapy, is crucial for treating NSCLC. Kirsten rat sarcoma virus (KRAS) is a poor prognostic factor in patients with NSCLC, particularly lung adenocarcinoma, where binding of conventional inhibitors to mutated KRAS proteins is challenging. Field profiles, research hotspots, and prospects for immunotherapy for patients with NSCLC-carrying KRAS mutations were uncovered in this study.MethodsMicrosoft Excel 2019, Bibliometrix, VOSviewer software, and Citespace were utilized to conduct a comprehensive scientometric analysis and understand a specific research field's knowledge base and frontiers aided by bibliometrics.ResultsBetween 2014 and 2023, 398 eligible documents in the English language were acquired using the WoSCC database, of which 113 and 285 were reviews and articles, respectively. The growth rate per year was 34.25 %. The most cited articles were from the United States, and China published the highest number of articles. Cancers was the journal, with increased publications in recent years. The keywords with the strongest citation bursts were analyzed using Citespace. "Immune checkpoint inhibitors," "co-occurring genomic alterations," and "KRAS" are among the research hotspots in this field.ConclusionUsing bibliometric and visual analyses, we examined immunotherapy for patients with KRAS-mutant NSCLC over the previous decade. The whole analysis showed a steady, quick increase in yearly publications in this area. Our findings will provide a roadmap for future research on the mechanisms of immunotherapy and immune checkpoint inhibitor action in treating KRAS-mutant NSCLC.

The Role of Emphysema on Postoperative Prognosis in Early-Stage Nonsmall Cell Lung Cancer.

Emphysema is generally considered a poor prognostic factor for patients with nonsmall cell lung cancer; however, whether the poor prognosis is due to highly malignant tumors or emphysema itself remains unclear. This study was designed to determine the prognostic value of emphysema in patients with early-stage nonsmall cell lung cancer. A total of 721 patients with clinical stage IA nonsmall cell lung cancer who underwent complete resection between April 2007 and December 2018 were retrospectively analyzed regarding clinicopathological findings and prognosis related to emphysema. The emphysematous and normal lung groups comprised 197 and 524 patients, respectively. Compared with the normal lung group, lymphatic invasion (23.9% vs. 14.1%, P = 0.003), vascular invasion (37.6% vs. 17.2%, P < 0.001), and pleural invasion (18.8% vs. 10.9%, P = 0.006) were observed more frequently in the emphysema group. Additionally, the 5-year overall survival rate was lower (77.1% vs. 91.4%, P < 0.001), and the cumulative incidence of other causes of death was higher in the emphysema group (14.0% vs. 3.50%, P < 0.001). Multivariable Cox regression analysis of overall survival revealed that emphysema (vs. normal lung, hazard ratio 2.02, P = 0.0052), age >70 years (vs. <70 years, hazard ratio 4.03, P < 0.001), and SUVmax >1.8 (vs. ≤1.8, hazard ratio 2.20, P = 0.0043) were independent prognostic factors. Early-stage nonsmall cell lung cancer with emphysema has a tendency for the development of highly malignant tumors. Additionally, emphysema itself may have an impact on poor prognosis.

Number of positive lymph nodes and lymph node ratio predict recurrence and survival in hypopharyngeal cancer based on SEER database and validation of real-world data.

This study investigated the impacts of the number of positive lymph nodes (NPLN) and lymph node ratio (LN ratio) for patients with hypopharyngeal squamous cell carcinoma (HPSCC) based on SEER database, which were validated in the real-world data of China. A total of 520 patients from SEER database were analyzed. Then 195 patients with pathologically stage III or IV HPSCC in our center were retrospectively studied. In the SEER database, NPLN ≥ 3 was found in 36.9% of patients. Multivariate analysis revealed that LN ratio ≥ 0.138 was significant with poorer overall survival (OS) (hazard ratio [HR] = 1.525, p = 0.001) and cancer-specific survival (CSS) (HR = 1.697, p < 0.001), so was the NPLN ≥ 3 (HR = 1.388, p = 0.013; HR = 1.479, p = 0.008). Patients with NPLN ≥ 3 were found in 103 (52.8%) in our center. Multivariate analysis confirmed a significant association regarding OS (p = 0.005) or CSS (p = 0.003) between patients with LN ratio ≥ 0.138 or not. In addition, disease recurrence rate differed significantly between the patients with NPLN ≥ 3 (27.2%) and NPLN < 3 (14.1%, p = 0.026). Moreover, postoperative chemoradiotherapy (CCRT) was significantly associated with better prognosis in patients with NPLN ≥ 3. In the SEER database, NPLN ≥ 3 and LN ratio ≥ 0.138 were independent poor prognostic factors for patients with HPSCC. Whereas identifying worldwide cut-off values for LN ratio is difficult and surgeon-dependent. In our cohort, adjuvant CCRT was beneficial for OS in patients with NPLN ≥ 3.

Abstract PO1-03-02: Impact of Body Mass Index (BMI) on the efficacy of different adjuvant chemotherapy schedules in patients with breast cancer: analysis from the randomized phase III GIM2 trial

Abstract Background: The long-term results of the Italian randomized phase III GIM2 study showed that, in women with node-positive breast cancer (BC), dose-dense (DD) chemotherapy significantly improved both disease-free survival (DFS) and overall survival (OS) compared with standard-interval (SI) chemotherapy. Obesity has been identified as an independent poor prognostic factor in patients with BC, with a potential negative impact on the efficacy and toxicity of systemic therapies. Nevertheless, the specific influence of body mass index (BMI) on the efficacy of different adjuvant chemotherapy schedules (DD or SI) remains a subject of debate. This analysis aimed to investigate this hypothesis in patients enrolled in the GIM2 trial. Methods: GIM2 was a randomized multicentric phase III trial that compared different chemotherapy schedule (DD vs SI) and regimen (FEC-P vs EC-P) in 2091 node-positive early breast cancer patients. BMI (kg/m2) was categorized as follows: &amp;lt; 18.5 (underweight), 18.5 to &amp;lt; 25 (lean), 25 to &amp;lt; 30 (overweight), and ≥ 30 (obese). The primary endpoint was to assess association between BMI and DFS and OS. Survival estimates were compared using the Kaplan-Meier method and log-rank test. Univariate and multivariable Cox proportional hazard models, adjusted for relevant prognostic factors, were used. Results: A total of 1925 patients were included in the present analysis, of whom 31.6% (n=632) were overweight and 19.3% (n=386) obese. Median age was 52 years. Overweight-obesity condition was significantly associated with postmenopausal status, greater representation of T2-T4 tumors with N &amp;gt; 2 in both patients in the DD and SI arm. After a median follow-up of 15.0 years (IQR 8.4-16.3), compared to patients with normal BMI, those who were overweight or obese at diagnosis had a higher risk of experiencing a DFS event (Hazard Ratio [HR] 1.11 95% CI 0.94-1.31 and HR 1.37 95%CI 1.14-1.65, respectively, p=0.003) and OS event (HR 1.11 95% CI 0.89-1.38 and HR 1.59 95%CI 1.26-2.01, respectively, p=0.0003). No significant interaction was found between BMI and treatment schedule in terms of DFS (p for interaction=0.56) nor OS (p for interaction=0.19). At the multivariate analysis, in the DD arm, adjusted HR (aHR) for DFS and for OS were 1.01 (95% CI 0.75- 1.35) and 1.04 (95% CI 0.72-1.52) for obese vs. normal BMI groups, and 0.88 (95% CI 0.68- 1.15) and 0.77 (95%CI 0.54-1.10) for overweight vs. normal BMI groups, respectively. In the SI arm, aHRs for DFS and OS were 1.24 (95% CI 0.94- 1.63) and 1.35 (95%CI 0.96- 1.90) for obese vs. normal BMI groups, and 1.04 (95%CI 0.82- 1.33) and 1.01 (95% CI 0.74-1.40) for overweight vs. normal BMI groups, respectively. Similar results were observed when considering hormone receptor-positive and negative BC separately. Conclusion: In the GIM2 trial, BMI was prognostic but not predictive of different benefit to adjuvant chemotherapy. In high-risk patients, DD schedule should be considered the preferred schedule irrespective of BMI. Citation Format: Francesca Poggio, Eva Blondeaux, Marco Tagliamento, Marta Perachino, Simone Nardin, Benedetta Conte, Sabino De Placido, Mario Giuliano, Valeria Forestieri, Michelino De Laurentiis, Adriano Gravina, Giancarlo Bisagni, Anita Rimanti, Anna Turletti, Cecilia Nisticò, Angela Vaccaro, Francesco Cognetti, Alessandra Fabi, Simona Gasparro, Ornella Garrone, Ylenia Urracci, Maria Grazia Alicicco, Mauro Mansutti, Paola Poletti, Pierpaolo Correale, Claudia Bighin, Fabio Puglisi, Filippo Montemurro, Giuseppe Colantuoni, Luca Boni, Matteo Lambertini, Lucia Del Mastro. Impact of Body Mass Index (BMI) on the efficacy of different adjuvant chemotherapy schedules in patients with breast cancer: analysis from the randomized phase III GIM2 trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-03-02.

Prognostic factors in patients with heart failure and sarcopenia: an observational retrospective study

BackgroundHeart failure (HF) prevalence increases with age, and sarcopenia is a poor prognostic factor in patients with HF. We aimed to evaluate the characteristics and prognostic factors in patients with HF and sarcopenia.ResultsWe retrospectively reviewed 256 consecutive patients admitted to our hospital for HF between May 2018 and May 2021, underwent dual-energy X-ray absorptiometry, and were diagnosed with sarcopenia. The primary endpoint was all-cause mortality. The prognoses and characteristics were evaluated and compared between patients with left ventricular ejection fraction (LVEF) < 50% (reduced LVEF, HF with reduced ejection fraction [HFrEF]) and those with LVEF ≥ 50% (preserved LVEF, HF with preserved ejection fraction [HFpEF]). 83 (32%) and 173 (68%) patients had HFrEF and HFpEF, respectively. The HFrEF group had fewer women, lower hypertension rates, higher ischemic heart disease rates, and brain natriuretic peptide (BNP) levels than did the HFpEF group. Kaplan–Meier analysis for all-cause death showed that the HFrEF group had a significantly worse prognosis than the HFpEF group [log-rank p = 0.002].ConclusionsIn patients with HF and sarcopenia, older age, higher New York Heart Association (NYHA) class, BNP levels, and reduced LVEF were independent predictors of death after evaluation. During the treatment of patients with HF and sarcopenia, it is necessary to manage treatment with close attention to BNP and LVEF.

The Association between the Level of Ankle-Brachial Index and the Risk of Poor Physical Function in Patients with Cardiovascular Disease.

The progression of atherosclerosis and decline in physical function are poor prognostic factors in patients with cardiovascular disease (CVD). The ankle-brachial index (ABI) is a widely used indicator of the degree of progression of atherosclerosis, which may be used to identify patients with CVD who are at risk of poor physical function. This study examined the association between ABI and poor physical function in patients with CVD. We reviewed the data of patients with CVD who completed the ABI assessment and physical function tests (6-min walking distance, gait speed, quadriceps isometric strength, and short physical performance battery). Patients were divided into five categories according to the level of ABI, and the association between ABI and poor physical function was examined using multiple logistic regression analysis. Additionally, restricted cubic splines were used to examine the nonlinear association between ABI and physical function. A total of 2982 patients (median [interquartile range] age: 71[62-78] years, 65.8% males) were included in this study. Using an ABI range of 1.11-1.20 as a reference, logistic regression analysis showed that ABI ≤ 1.10 was associated with poor physical function. The restricted cubic spline analysis showed that all physical functions increased with an increase in ABI level. The increase in physical function plateaued at an ABI level of approximately 1.1. ABI may be used to identify patients with poor physical function. ABI levels below 1.1 are potentially associated with poor physical function in patients with CVD.

CACNA2D1 regulates the progression and influences the microenvironment of colon cancer.

Calcium voltage-gated channel auxiliary subunit alpha 2/delta 1 (CACNA2D1), a gene encoding a voltage-gated calcium channel, has been reported as an oncogene in several cancers. However, its role in colon cancer (CC) remains unclear. This study aimed to investigate the function of CACNA2D1 and its effect on the microenvironment in CC. Immunohistochemistry (IHC) analysis was performed on samples collected from 200 patients with CC who underwent curative colectomy. Knockdown experiments were performed using CACNA2D1 siRNA in the human CC cell lines HCT116 and RKO, and cell proliferation, cycle, apoptosis, and migration were then analyzed. The fibroblast cell line CCD-18Co was co-cultured with CC cell lines to determine the effect of CACNA2D1 on fibroblasts and the relationship between CACNA2D1 and the cancer microenvironment. Gene expression profiles of cells were analyzed using microarray analysis. IHC revealed that high CACNA2D1 expression was an independent poor prognostic factor in patients with CC and that CACNA2D1 expression and the stroma are correlated. CACNA2D1 depletion decreased cell proliferation and migration; CACNA2D1 knockdown increased the number of cells in the sub-G1 phase and induced apoptosis. CCD-18Co and HCT116 or RKO cell co-culture revealed that CACNA2D1 affects the cancer microenvironment via fibroblast regulation. Furthermore, microarray analysis showed that the p53 signaling pathway and epithelial-mesenchymal transition-associated pathways were enhanced in CACNA2D1-depleted HCT116 cells. CACNA2D1 plays an important role in the progression and the microenvironment of CC by regulating fibroblasts and may act as a biomarker for disease progression and a therapeutic target for CC.

Abstract 7363: Clinical, genomic, transcriptomic and immunologic profile of BRAF mutant colorectal tumors

Abstract Background: Colorectal cancer (CRC) is the second leading cause of cancer-related death worldwide. BRAF, a protein kinase of the Mitogen-Activated Protein Kinase (MAPK) pathway, is mutated in 12% of colorectal cancers and is a poor prognostic factor for patients. BRAF mutations at the V600 codon are most studied but non-V600 BRAF mutations also exist and behave differently. BRAF V600 CRC treated with BRAF+MEK inhibitors show 12% response rates while we observe 65% response rates in BRAF V600 Melanoma. Additionally, no approved targeted therapies exist for non-V600 BRAF mutant cancers and retrospective studies show poorer PFS with BRAF+MEK inhibitors vs BRAF V600 cancers. We interrogated publicly available data of BRAF mutant CRC to uncover differences in the tumor microenvironment and signalling pathways of BRAF V600 and non-V600 tumors in hopes of uncovering better treatments. Methods: We analyzed the clinical and genomic profile of BRAF mutant CRC tumors from the GENIE v12 data. Gene Set Enrichment Analysis was performed on RNAseq from the TCGA data (discovery cohort) and the combined data from CPTAC and Sidra-LUMC data (validation cohort). We investigated the composition of tumor infiltrating immune cells using CIBERSORTx (deconvolution algorithm for bulk RNAseq). Results: Non-V600 mutations (n=219/1061) were most represented in patients of Asian or Black race compared to White patients (p&amp;lt;0.0001) and importantly, were found in younger patients (p&amp;lt;0.0001). We identified n=67 and n=74 BRAF mutant RNAseq samples in the discovery and validation cohorts, respectively. In the discovery cohort: BRAF V600 CRC were enriched for Interferon Gamma Signaling, Complement pathway, and IL6 JAK STAT3 Signaling (p&amp;lt;0.05) while the non-V600 BRAF mutant CRC showed an enrichment for Wnt-beta Catenin, Notch, and Hedgehog Signaling pathways (p&amp;lt;0.05). In the validation cohorts these same pathways were enriched in V600 and non-V600 BRAF mutant tumors. Interestingly, enrichment of genes co-mutated (GENIE data) in non-V600 BRAF mutant CRC also revealed the Wnt pathway. Non-V600 CRC tumors have a higher proportion of M0 macrophages (p=0.0035) and CD4 memory resting T cells (p&amp;lt;0.0001) while patients with V600 CRC have higher proportions of CD8 T cells (p=0.006) and activated mast cells (p=0.0341). Conclusion: No optimal therapeutic strategies have been defined for these potentially actionable non-V600 BRAF mutant CRCs. By exploring the multi-omic landscape of these tumors we have identified unique characteristics of non-V600 BRAF mutant CRC that could be therapeutically exploited. Citation Format: Emmanuelle Rousselle, Suzanne Kazandjian, April Rose. Clinical, genomic, transcriptomic and immunologic profile of BRAF mutant colorectal tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7363.

Abstract 3730: Impact of proton pump inhibitor on ICI with or without chemotherapy for NSCLC with high PD-L1 TPS

Abstract Background and Aim: Immune checkpoint inhibitors (ICIs) have been widely used for the initial treatment of non-small cell lung cancer (NSCLC). Although both ICI monotherapy and the combination of ICI plus chemotherapy (chemo-ICI) are promising therapeutic options for patients with a programmed cell death ligand-1 tumor proportion score of 50% or higher (high PD-L1), the patient's clinical background and biomarkers differentiating the two options are still not well-defined. In our prior research, we found that a history of proton pump inhibitor (PPI) use independently have negative impact with significantly shorter overall survival (OS) and progression-free survival (PFS) in NSCLC patients harboring high PD-L1 with pembrolizumab monotherapy, but not with chemo-ICI. However, this OS data remain immature. Therefore, in our current study, we extended the follow-up period and conduct additional analysis including OS data to confirm this trend. Method: Advanced NSCLC patients with high PD-L1 who had received pembrolizumab or chemo-ICI as the first-line treatment between March 2017 and December 2020 at 13 hospitals in Japan were analyzed. Survival outcomes were estimated using the Kaplan- Meier method and were compared using the log-rank test. Results: A total of 425 patients with NSCLC were included in the study, with 271 patients (median [range] age, 72 [43-90] years; 215 [79%] men) receiving pembrolizumab monotherapy as their first-line treatment and 154 patients (median [range] age, 69 [36-86] years; 121 [79%] men) receiving chemo-ICI as their first-line treatment. The median follow-up duration was 22.8 months. Among patients with a history of PPI use, both median PFS (19.3 months vs. 6.8 months; HR, 0.53; 95% CI, 0.35-0.78; P = .003) and the median OS(not reached vs. 20.4 months; HR, 0.53; 95% CI, 0.34-0.85; P = .04) were significantly longer in the chemo-ICI group compared to the pembrolizumab monotherapy group. For patients without a history of PPI use, both median PFS (11.4 months vs. 10.8 months; HR, 0.99; 95% CI, 0.76-1.3; P = .36) and the median overall survival (42.2 months vs. 29.9 months, HR, 0.84; 95% CI, 0.62-1.16; P = .33) showed no significant differences between the groups. Discussion and Conclusion: This retrospective study showed that a concomitant treatment with PPI is poor prognostic factor in patients harboring high PD-L1 and treated with ICI monotherapy compared with chemo-ICI in Japanese cohort and this tendency is durable in long-term follow-up. These results indicate that when deciding on an ICI treatment, with or without chemotherapy, it is essential to take into account a concomitant treatment with PPI. Citation Format: Ryo Sawada, Hayato Kawachi, Tadaaki Yamada, Motohiro Tamiya, Yoshiki Negi, Yasuhiro Goto, Akira Nakao, Shinsuke Shiotsu, Takayuki Takeda, Asuka Okada, Taishi Harada, Koji Date, Yusuke Chihara, Isao Hasegawa, Takashi Kijima, Koichi Takayama. Impact of proton pump inhibitor on ICI with or without chemotherapy for NSCLC with high PD-L1 TPS [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3730.

Pleomorphic carcinoma of the lung revealed by uncommon colonic metastasis: An exceptional case report with literature review.

Lung pleomorphic carcinoma is a rare and aggressive cancer that uncommonly metastasizes to the colon and only a few case reports have been published thus far. We present an exceptional case of colon metastasis from lung pleomorphic carcinoma in a 68-year-old man which was revealed by large bowel perforation, and we review the previous three published cases. Metastasis to the bowel from primary lung malignancy often lacks specific symptoms which result in delayed diagnosis. Bowel metastasis is a poor prognostic factor in patients with lung pleomorphic carcinoma, regardless of management strategy.

High HER2 Intratumoral Heterogeneity Is a Predictive Factor for Poor Prognosis in Early-Stage and Locally Advanced HER2-Positive Breast Cancer.

Breast cancer tumors frequently have intratumoral heterogeneity (ITH). Tumors with high ITH cause therapeutic resistance and have human epidermal growth factor receptor 2 (HER2) heterogeneity in response to HER2-targeted therapies. This study aimed to investigate whether high HER2 heterogeneity levels were clinically related to a poor prognosis for HER2-targeted adjuvant therapy resistance in primary breast cancers. This study included patients with primary breast cancer (n = 251) treated with adjuvant HER2-targeted therapies. HER2 heterogeneity was manifested by the shape of HER2 fluorescence in situ hybridization amplification (FISH) distributed histograms with the HER2 gene copy number within a tumor sample. Each tumor was classified into a biphasic grade graph (high heterogeneity [HH]) group or a monophasic grade graph (low heterogeneity [LH]) group based on heterogeneity. Both groups were evaluated for disease-free survival (DFS) and overall survival (OS) for a median of ten years of annual follow-up. Of 251 patients with HER2-positive breast cancer, 46 (18.3%) and 205 (81.7%) were classified into the HH and LH groups, respectively. The HH group had more distant metastases and a poorer prognosis than the LH group (DFS: p < 0.001 (HH:63% vs. LH:91% at 10 years) and for the OS: p = 0.012 (HH:78% vs. LH:95% at 10 years). High HER2 heterogeneity is a poor prognostic factor in patients with HER2-positive breast cancer. A novel approach to heterogeneity, which is manifested by the shape of HER2 FISH distributions, might be clinically useful in the prognosis prediction of patients after HER2 adjuvant therapy.

Overall survival and short-term efficacy analysis of cervical squamous cell carcinoma with skeletal muscle and 18F-FDG PET/CT parameters

2-[18F]fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) can provide tumor biological metabolism and skeletal muscle composition information. The aim of this study was to evaluate overall survival (OS) and short-term efficacy of cervical squamous cell carcinoma combining tumor biological metabolism and skeletal muscle composition parameters. Eighty two patients with cervical squamous cell carcinoma were included in the study, who received 18F-FDG PET/CT scans before treatment. Clinical characteristics, tumor biological metabolism parameters [standardized uptake value, metabolic tumor volume (MTV), total lesion glycolysis, heterogeneity of tumors, etc.] and body composition parameters were recorded. The survival analysis of cervical squamous cell carcinoma patients was performed by univariate and multivariate analysis. A combined model included clinical indicators, tumor metabolism parameters and sarcopenia was constructed to evaluate OS of patients. According to the Response Evaluation Criteria in Solid Tumours version 1.1, the relationship between sarcopenia with tumor metabolism parameters and short-term efficacy was investigated in subgroup. The results indicate that sarcopenia and high value of the sum of MTV of lesions and metastases (MTVtotal) were poor prognostic factors in patients with cervical squamous cell carcinoma. The combination of sarcopenia, MTVtotal and clinical factors provided an improved prediction of OS especially in the long term after treatment. Nutritional status of the patients and tumor metabolism may not affect the short-term efficacy of chemoradiotherapy in cervical squamous cell carcinoma patients.

Cytomegalovirus immunoglobulin serology prevalence in patients with newly diagnosed multiple myeloma treated within the GMMG-MM5 phase III trial

ABSTRACT Objectives The seroprevalence of antibodies against Cytomegalovirus (CMV) is an established poor prognostic factor for patients receiving an allogeneic stem cell transplantation. However, the impact of CMV serology on outcome after autologous stem cell transplantation remains unknown. Methods Here, we analyzed the CMV immunoglobulin (Ig) serology of 446 newly-diagnosed multiple myeloma (MM) patients of the GMMG-MM5 phase III trial with a median follow-up of 58 months. Results CMV IgG and IgM positivity was seen in 51% and 6% of the patients, respectively. In multivariate analysis CMV IgG and CMV IgM serology show an age-depending effect for PFS. We identified positive CMV IgG/positive CMV IgM serology as an age-depending beneficial factor on PFS. Discussion Younger patients with a positive CMV IgG/positive CMV IgM serology experienced a favorable effect on PFS, whereas a positive CMV IgG/positive CMV IgM serology at older age has a disadvantageous effect on PFS.

Correlative factors of poor prognosis and abnormal cellular immune function in patients with Alzheimer's disease.

Alzheimer's disease (AD) is a serious disease causing human dementia and social problems. The quality of life and prognosis of AD patients have attracted much attention. The role of chronic immune inflammation in the pathogenesis of AD is becoming more and more important. To study the relationship among cognitive dysfunction, abnormal cellular immune function, neuroimaging results and poor prognostic factors in patients. A retrospective analysis of 62 hospitalized patients clinical diagnosed with AD who were admitted to our hospital from November 2015 to November 2020. Collect cognitive dysfunction performance characteristics, laboratory test data and neuroimaging data from medical records within 24 h of admission, including Mini Mental State Examination Scale score, drawing clock test, blood T lymphocyte subsets, and neutrophils and lymphocyte ratio (NLR), disturbance of consciousness, extrapyramidal symptoms, electroencephalogram (EEG) and head nucleus magnetic spectroscopy (MRS) and other data. Multivariate logistic regression analysis was used to determine independent prognostic factors. the modified Rankin scale (mRS) was used to determine whether the prognosis was good. The correlation between drug treatment and prognostic mRS score was tested by the rank sum test. Univariate analysis showed that abnormal cellular immune function, extrapyramidal symptoms, obvious disturbance of consciousness, abnormal EEG, increased NLR, abnormal MRS, and complicated pneumonia were related to the poor prognosis of AD patients. Multivariate logistic regression analysis showed that the decrease in the proportion of T lymphocytes in the blood after abnormal cellular immune function (odd ratio: 2.078, 95% confidence interval: 1.156-3.986, P < 0.05) was an independent risk factor for predicting the poor prognosis of AD. The number of days of donepezil treatment to improve cognitive function was negatively correlated with mRS score (r = 0.578, P < 0.05). The decrease in the proportion of T lymphocytes may have predictive value for the poor prognosis of AD. It is recommended that the proportion of T lymphocytes < 55% is used as the cut-off threshold for predicting the poor prognosis of AD. The early and continuous drug treatment is associated with a good prognosis.

Should Advanced Age Preclude Surgical Treatment of Gastrointestinal Stromal Tumor?

Introduction: Surgical resection is a gold standard treatment for gastrointestinal stromal tumors (GISTs). It can be performed by minimally invasive surgery approach in most of the patients. It has been shown that advanced age is not a clear poor prognostic factor in patients who underwent surgery for GIST. We hypothesized that elderly patients undergo elective surgery less often compared to younger population. We aim to evaluate the safety, efficacy and oncological results of GIST treatment in the elderly population in our Medical Center. Materials and Methods: All patients who underwent surgery for GIST in Shamir Medical Center from January 1, 2016, to July 31, 2023, were included in the study. The patients were divided into 2 groups. Group 1 included patients younger than 75 years, while patients older than 75 years were included in Group 2. The groups were compared according to demographics, clinical and surgical parameters, complications, and pathology results. Results: Overall, 49 patients were included in the study. Group 1 included 28 patients and Group 2 included 21 patients. Group 2 patients more often underwent emergency surgery (52.4% versus 14.3%, P < .05) and had increased open surgery rate (19% versus 0%, P < .05). No difference between the groups was noted in surgical parameters, complications, and length of hospital stay. Tumor size, number of mitoses, level of ki67%, and involvement of surgical margins were not significantly different. However, in Group 2 patients, tumor size was larger and there was a trend toward higher rate of ki67 > 5%. Conclusion: Elderly patients with GIST are less frequently undergoing electively surgery and relatively often undergo open surgery. Frequency of complications is similar in elderly patients compares to younger patients group.

Inpatient outcomes for lung cancer patients presenting with superior vena cava thrombosis

Background A specific cause of superior vena cava (SVC) syndrome, SVC thrombosis, is a rare but known complication in cancer patients. Early identification and management of SVC thrombosis in lung cancer patients may lead to improved patient outcomes and a reduction in healthcare costs. Methods We studied the racial and socioeconomic differences, length of stay, total hospital charges, and all-cause mortality outcomes in patients with lung cancer with and without SVC thrombosis using data from the National Inpatient Sample. Statistical analysis was performed on STATA. Results A total of 480,750 patients were hospitalized for lung cancer; 720 (0.15%) of these patients had SVC thrombosis. The lung cancer with SVC thrombosis cohort had a statistically higher proportion of Black patients. Patients with lung cancer presenting with SVC thrombosis had an increased hospital length of stay (10 vs 6 days, P < 0.001) and cost ($117,320 vs $80,806, P < 0.005) compared to those without SVC thrombosis. All-cause mortality in patients with lung cancer was 7.7% and the presence of SVC thrombosis significantly increased the odds of inpatient mortality (18.0%). Nonwhite races were associated with higher odds of mortality in lung cancer admissions. Conclusion Race, insurance type, and comorbidities impacted the likelihood of developing SVC thrombosis in patients with lung cancer. SVC thrombosis is a poor prognostic factor for patients with lung cancer. Further studies to evaluate these disparities are warranted.

MTHFD1 regulates the NADPH redox homeostasis in MYCN-amplified neuroblastoma.

MYCN amplification is an independent poor prognostic factor in patients with high-risk neuroblastoma (NB). Further exploring the molecular regulatory mechanisms in MYCN-amplified NB will help to develop novel therapy targets. In this study, methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) was identified as the differentially expressed gene (DEG) highly expressed in MYCN-amplified NB, and it showed a positive correlation with MYCN and was associated with a poor prognosis of NB patients. Knockdown of MTHFD1 inhibited proliferation and migration, and induced apoptosis of NB cells in vitro. Mouse model experiments validated the tumorigenic effect of MTHFD1 in NB in vivo. In terms of the mechanism, ChIP-qPCR and dual-luciferase reporter assays demonstrated that MTHFD1 was directly activated by MYCN at the transcriptional level. As an important enzyme in the folic acid metabolism pathway, MTHFD1 maintained the NADPH redox homeostasis in MYCN-amplified NB. Knockdown of MTHFD1 reduced cellular NADPH/NADP+ and GSH/GSSG ratios, increased cellular reactive oxygen species (ROS) and triggered the apoptosis of NB cells. Moreover, genetic knockdown of MTHFD1 or application of the anti-folic acid metabolism drug methotrexate (MTX) potentiated the anti-tumor effect of JQ1 both in vitro and in vivo. Taken together, MTHFD1 as an oncogene is a potential therapeutic target for MYCN-amplified NB. The combination of MTX with JQ1 is of important clinical translational significance for the treatment of patients with MYCN-amplified NB.

Clinical efficacy of intratympanic steroid injection for treating idiopathic sudden sensorineural hearing loss.

Idiopathic sudden sensorineural hearing loss (ISSNHL) is an emergency that causes permanent hearing loss if timely treatment is not provided. However, the evidence supporting the effect of intratympanic steroid injection (ITSI) starting time on hearing outcome is limited. We retrospectively enrolled 582 patients with ISSNHL who were treated with ITSIs and reviewed their clinical and audiological variables. The relationship between ITSI starting time and hearing recovery was analyzed. The mean starting time of ITSI was 13.17 ± 16.53 days. The overall hearing recovery rate was 55.15% (recovery = mean hearing level gain of ≥10 dB). The recovery rates were 79.2%, 67.4%, 50%, 36.6%, and 17.8% for the ITSI starting times of 1 to 3, 4 to 7, 8 to 14, 15 to 28, and ≥29 days, respectively. A multivariate analysis revealed that ITST starting time (odds ratio [OR] = 0.94, 95% CI, 0.92-0.96, p < 0.001) and salvage therapy (OR = 0.55, 95% CI, 0.35-0.86, p = 0.009) were independent poor prognostic factors for patients with ISSNHL. Earlier ITSI treatment is associated with a higher hearing recovery rate. Comorbidities and post-ITSI complications were nonsignificant independent risk factors.