Predictors Of Better Overall Survival Research Articles

Volumetric parameters of the primary tumor and whole-body tumor burden derived from baseline 18F-FDG PET/CT can predict overall survival in non-small cell lung cancer patients: initial results from a single institution

BackgroundMetabolic tumor volume (MTV) and total lesion glycolysis (TLG) are volumetric parameters derived from 18F-FDG PET/CT, suggested to have a prognostic value in cancer patients. Our study aimed to test whether these volumetric parameters of the primary tumor and whole-body tumor burden (WBTB) can predict overall survival (OS) in non-small cell lung cancer (NSCLC) patients.Materials and methodsThirty biopsy-proven NSCLC patients who had not begun anti-tumor therapy were included in this prospective study. A baseline 18F-FDG PET/CT study was acquired. Scans were interpreted visually and semi-quantitatively by drawing a 3D volume of interest (VOI) over the primary tumor and all positive lesions to calculate metabolic, volumetric parameters, and WBTB. The PET parameters were used to stratify patients into high- and low-risk categories. The overall survival was estimated from the date of scanning until the date of death or last follow-up.ResultsAt a median follow-up of 22.73 months, the mean OS was shorter among patients with higher tu MTV and tu TLG and high WBTB. High WB TLG was independently associated with the risk of death (p < 0.025). Other parameters, e.g., SUVmax, SUVpeak, and SUVmean, were not predictive of outcomes in these patients. Conclusion: In patients with NSCLC, tu MTV, tu TLG, and WBTB determined on initial staging 18F-FDG PET/CT seems to be a strong, independent imaging biomarker to predict OS, superior to the clinical assessment of the primary tumor. The WB TLG was found to be the best predictor of OS.

Prognostic factors for overall survival and intracranial progression in patients with renal cancer metastasis into the brain after neurosurgical treatment

Introduction. Treatment of patients with brain metastases is an important problem that should be considered in the framework of combination approach. Introduction of new techniques of drug therapy as well as radiotherapy and neurosurgical treatment allows to significantly increase patient survival. Effective drug therapy and local control of brain metastases are of utmost importance in prediction of overall survival and patient quality of life.Aim. To investigate the prognostic factors for overall survival and intracranial progression (local recurrences, distant metastases) in patients with brain metastases of renal cancer after neurosurgical resection.Materials and methods. Retrospective analysis of the treatment results of 114 patients with metastatic brain lesions due to renal cancer who underwent neurosurgical resection (NSR) at the N. N. Blokhin National medical Research Center of Oncology was performed. Clinical data of 102 (89.5 %) of 114 patients for whom data on survival was available were evaluated. Among them, 80 (78.4 %) of patients died, 22 (21.5 %) are under observation. Extracranial disease status at the time of NSR was known in 82 (71.9 %) patients: 45 (54.8 %) patients had extracranial metastases, and 37 (45.1 %) did not. Total resection of brain metastases with perifocal and perivascular zones was performed in 92 (90.1 %) patients; in other cases, fragmental lesion resection was performed.Results. median overall survival after NSR was 13.8 months (95 % confidence interval 10.3–18.6). per study data, factors affecting overall survival of patients with brain metastases of renal cancer after neurosurgical resection were presence / absence of extracranial metastases and patient’s functional status. Local recurrences in the postoperative cavity after NSR were observed in 24 (21 %) of 114 patients. median time of local recurrence was not achieved. Statistically significant factor of high risk of recurrence in the postoperative cavity was presence of lesions with maximal diameter ≥2 cm. Development of new (distant) metastases was observed in 31 (27.2 %) of 114 patients. median survival without distant metastases in patients with brain metastases after NSR was not achieved. frequencies of distant metastases at 6, 12 and 24 months were 15.5; 24.1 and 35.8 % respectively. per multifactor analysis, factors affecting development of distant metastases in the brain after NSR are multiple metastatic brain lesions and presence of extracranial metastases.Conclusion. Neurosurgical resection in patients with cerebral metastases of renal cancer in the total group leads to median overall survival of 13.8 months. predictors of better overall survival are absence of extracranial metastases and high functional status.

The derived neutrophil to lymphocyte ratio can be the predictor of prognosis for COVID-19 Omicron BA.2 infected patients.

Several systemic inflammatory biomarkers have been associated with poor overall survival (OS) and disease severity in patients with coronavirus disease 2019 (COVID-19). However, it remains unclear which markers are better for predicting prognosis, especially for COVID-19 Omicron BA.2 infected patients. The present study aimed to identify reliable predictors of prognosis of COVID-19 Omicron BA.2 from inflammatory indicators. A cohort of 2645 COVID-19 Omicron BA.2 infected patients were retrospectively analyzed during the Omicron BA.2 surge in Shanghai between April 12, 2022, and June 17, 2022. The patients were admitted to the Shanghai Fourth People's Hospital, School of Medicine, Tongji University. Six systemic inflammatory indicators were included, and their cut-off points were calculated using maximally selected rank statistics. The analysis involved Kaplan-Meier curves, univariate and multivariate Cox proportional hazard models, and time-dependent receiver operating characteristic curves (time-ROC) for OS-associated inflammatory indicators. A total of 2347 COVID-19 Omicron BA.2 infected patients were included. All selected indicators proved to be independent predictors of OS in the multivariate analysis (all P < 0.01). A high derived neutrophil to lymphocyte ratio (dNLR) was associated with a higher mortality risk of COVID-19 [hazard ratio, 4.272; 95% confidence interval (CI), 2.417-7.552]. The analyses of time-AUC and C-index showed that the dNLR (C-index: 0.844, 0.824, and 0.718 for the 5th, 10th, and 15th day, respectively) had the best predictive power for OS in COVID-19 Omicron BA.2 infected patients. Among different sub-groups, the dNLR was the best predictor for OS regardless of age (0.811 for patients aged ≥70 years), gender (C-index, 0.880 for men and 0.793 for women) and disease severity (C-index, 0.932 for non-severe patients and 0.658 for severe patients). However, the platelet to lymphocyte ratio was superior to the other indicators in patients aged <70 years. The prognostic ability of the dNLR was higher than the other evaluated inflammatory indicators for all COVID-19 Omicron BA.2 infected patients.

52. Novel recurrent cytogenetic abnormalities predict overall survival in tetraploid/near-tetraploid MDS/AML

<h3>Introduction</h3> Tetraploidy (4n=92 chromosomes) and near-tetraploidy (81-103 chromosomes) (T/NT) are uncommon cytogenetic events in MDS/AML (∼1%). Most patients are older adults with a male predominance and poor prognosis. Recurrent abnormalities associated with T/NT MDS/AML include -5/del(5q), -7/del(7q), -17/add(17p)/i(17q), -18, +8, and +21. However, other clinically-relevant abnormalities likely remain 'hidden' in long strings of cytogenetic nomenclature that are difficult to discern by visual inspection. To date, no studies have had the statistical power and computational methodology to identify novel recurrent abnormalities associated with T/NT karyotypes that predict overall survival (OS). <h3>Methods</h3> We used Cytogenetic Pattern Sleuth (CytoGPS), a publicly-available bioinformatic tool (http://cytogps.org) that we developed, to convert ISCN karyotypes from a combined cohort of 75 T/NT MDS/AML cases from two institutions (OSU and MDACC) into a binary Loss-Gain-Fusion model, which is analyzable using computational methods. <h3>Results</h3> We performed univariate analyses on the clinical and karyotypic data. Age (continuous variable, p=0.032), prior treatment (p=0.011), and cohort (p=0.025) were associated with OS; age ?60 years (p=0.316), gender (p=0.916), karyotypic complexity (p=0.175), time from diagnosis to identification of the T/NT karyotype (p=0.419), and T/NT clone size (p=0.316) had no effect. Univariate analyses of the CytoGPS results demonstrated that -5, -16, -18, del(11)(p15.1p15.4), del(13)(q12.11q22.3), and +8 were associated with poorer OS (unadjusted p<0.05). Next we used the results of univariate analyses to build multivariate models of OS. <h3>Conclusion</h3> The best predictor of OS in T/NT MDS/AML patients is the presence of any one of six cytogenetic abnormalities: -5, -16, -18, del(11)(p15.1p15.4), del(13)(q12.11q22.3), +8.

Value of the Preoperative D-Dimer to Albumin Ratio for Survival and Recurrence Patterns in Gastric Cancer.

D-dimer (DDI) and albumin are prognostic markers for numerous cancers; however, the predictive value of the preoperative DDI-to-albumin ratio (DAR) on the survival and recurrence patterns of gastric cancer (GC) remains unclear. The aim of this study was to explore the prognostic value of the DAR in GC. Our study included 1766 patients with GC, divided into training and testing cohorts at a ratio of 7:3. Patients were classified into either a high-DAR group (> 0.0145) or low-DAR group (≤ 0.0145) according to the cut-off value of receiver operating characteristic (ROC) curve analysis. The relationship between the DAR and recurrence pattern was analyzed in stage II/III patients. Eight preoperative hematological factors were included and 17 composite inflammatory markers were constructed. ROC and random forest analyses indicated that among 17 markers, DAR was the best predictor for overall survival (OS) in GC (p<0.01). High DAR was significantly associated with poor OS (hazard ratio [HR] 1.89, p<0.001) and recurrence-free survival (RFS; HR 1.85, p<0.001). Subgroup analysis showed no differences in OS and RFS between the high- and low-DAR groups in stage I or pT1/2 or pN0/1 patients; however, in stage II/III or pT3/4 or pN2/3 patients, the high-DAR group had shorter OS and RFS rates than the low-DAR group (p<0.001). Similar results were found in the testing cohort. According to the multivariate analysis based on the training cohort, five indices, including DAR, cT stage, cN stage, age and body mass index (BMI), were incorporated to establish a nomogram model to predict the long-term prognosis of GC. The model showed comparable forecast performance in predicting OS (C-index: 0.773 vs. 0.786) and RFS (C-index: 0.788 vs. 0.795) compared with pTNM. Recurrence pattern analysis in stage II/III patients showed that the high-DAR group had a higher incidence of peritoneal implantation and early recurrence (ER) than the low-DAR group, and the post-recurrence survival in the high-DAR group was significantly shorter than that in the low-DAR group (p=0.016). The preoperative DAR is a new biomarker for the long-term survival prediction of GC. In advanced GC, a preoperative DAR > 0.0145 aids the timely detection of ER and peritoneal recurrence after surgery, thus guiding individual follow-up strategies.

A gene expression signature in HER2+ breast cancer patients related to neoadjuvant chemotherapy resistance, overall survival, and disease-free survival.

To identify prognostic markers for treatment and survival in HER2+ patients. Patients treated with neoadjuvant chemotherapy were assigned to sensitive and resistant groups based on their treatment response. Differentially expressed genes (DEGs) were identified using RNA-seq analysis. KEGG pathway, gene ontology, and interactome analyses were performed for all DEGs. An enrichment analysis Gene set enrichment analysis was performed. All DEGs were analyzed for overall (OS) and disease-free survival (DFS). A total of 94 DEGs were related to treatment resistance. Survival analysis showed that 12 genes (ATF6B, DHRS13, DIRAS1, ERAL1, GRIN2B, L1CAM, IRX3, PRTFDC1, PBX2, S100B, SLC9A3R2, and TNXB) were good predictors of disease-free survival, and eight genes (GNG4, IL22RA2, MICA, S100B, SERPINF2, HLA-A, DIRAS1, and TNXB) were good predictors of overall survival (OS). We highlighted a molecular expression signature that can differentiate the treatment response, overall survival, and DFS of patients with HER2+ breast cancer.

Sex as a prognostic factor in adult-type diffuse gliomas: an integrated clinical and molecular analysis according to the 2021 WHO classification.

To investigate whether type-specific sex differences in survival exist independently of clinical and molecular factors in adult-type diffuse gliomas according to the 2021 World Health Organization (WHO) classification. A retrospective chart and imaging review of 1325 patients (mean age, 54 ± 15years; 569 females) with adult-type diffuse gliomas (oligodendroglioma, IDH-mutant, and 1p/19q-codeleted, n = 183; astrocytoma, IDH-mutant, n = 211; glioblastoma, IDH-wildtype, n = 800; IDH-wildtype diffuse glioma, NOS, n = 131) was performed. The demographic information, extent of resection, imaging data, and molecular data including O6-methylguanine-methyltransferase promoter methylation (MGMT) promotor methylation were collected. Sex differences in survival were analyzed using Cox analysis. In patients with glioblastoma, IDH-wildtype, female sex remained as an independent predictor of better overall survival (hazard ratio = 0.91, P = 0.031), along with age, histological grade 4, MGMT promoter methylation status, and gross total resection. Female sex showed a higher prevalence of MGMT promoter methylation (40.2% vs 32.0%, P = 0.017) but there was no interaction effect between female sex and MGMT promoter methylation status (P-interaction = 0.194), indicating independent role of female sex. The median OS for females were 19.2months (12.3-35.0) and 16.2months (10.5-30.6) for males. No sex difference in survival was seen in other types of adult-type diffuse gliomas. There was a female survival advantage in glioblastoma, IDH-wildtype, independently of clinical data or MGMT promoter methylation status. There was no sex difference in survival in other types of adult-type diffuse gliomas, suggesting type-specific sex effects solely in glioblastoma, IDH-wildtype.

Impact of Marital Status on Prognosis of Patients With Invasive Breast Cancer: A Population-Based Study Using SEER Database.

ObjectiveThis study aimed to investigate the prognostic roles of marital status in patients with invasive breast cancer. Method: We extracted the data of patients with invasive breast cancer who were diagnosed during 2010–2015 and had complete staging and molecular typing from the Surveillance, Epidemiology, and End Results (SEER)-18 database. Kaplan–Meier curve method and Cox regression analysis were performed to investigate the differences in breast cancer–specific survival (BCSS) and overall survival (OS) in the total population and various subgroups with different marital statuses.ResultsAmong the 324,062 patients with breast cancer in this study, 55.0%, 40.0%, and 5.0% were married, unmarried, and unknown, respectively; 51.8%, 32.2%, 10.5%, and 5.5% were patients with Stages I, II, III, and IV breast cancer, respectively. The 5-year BCSS and OS of married patients were 92.6% and 88.1%, respectively, higher than those of unmarried patients (88.3% and 78.1%, P < 0.001). After adjustment for sex, age, T and N stages, histological grade, insurance status, race, year of diagnosis, and molecular subtypes, married status was an independent predictor of better BCSS [hazard ratio (HR) = 0.775, 95% confidence interval (CI) = 0.753–0.797, P < 0.001) and OS (HR = 0.667, 95% CI = 0.653–0.681, P < 0.001). After multivariate analysis of various subgroups of sex, age, stage, histological grade, insurance status, race, and molecular subtype, married status was an independent predictor of better BCSS in all subgroups except for Grade IV, age < 35 years, and uninsured subgroups. Marital status was an independent predictor of better OS in all subgroups except the subgroup with age <35 years.ConclusionsIn conclusion, marital status was an independent prognostic factor for breast cancer. The unmarried patients with breast cancer had a worse prognosis, except for the subgroup with age <35 years. Hence, unmarried patients with breast cancer and age ≥35 years may need additional psychosocial and emotional support to achieve more prolonged survival, besides active treatment of primary disease.

A Study on Early Death Prognosis Model in Adult Patients with Secondary Hemophagocytic Lymphohistiocytosis.

Background The mortality risks for secondary hemophagocytic lymphohistiocytosis in the induction stage and investigated prognostic factors need to be further discussed. Objective The aim of this study is to establish a clinical model for predicting early death in adult patients with secondary hemophagocytic lymphohistiocytosis. Design, Participants, and Main Measures. The baseline characteristics, laboratory examination results, and 8-week survival rate of 139 adult sHLH patients diagnosed from January 2018 to December 2018 were analyzed retrospectively, and a prognostic model was constructed with low-risk (score 0–2), medium-risk (score 3), and high-risk (score ≥ 4) as parameters. Key Results. Univariate analysis confirmed that early death was not related to the type of HLH but significantly related to the patient's response to first-line treatment. The peripheral blood cell count was significantly decreased, C-reactive protein was higher, glutamyl transpeptidase and total bilirubin were higher, albumin was significantly lower, urea nitrogen was higher, hypocalcemia and hyponatremia, deep organ hemorrhage and D-dimer increased, cardiac function damage and HLH central involvement, sCD25 increased, and EB virus infection were predictive factors of early death. In the multivariate model, patients' response to first-line treatment was a good predictor of overall survival, and hypocalcemia and deep organ bleeding were associated with poor survival. The risk factors were scored and graded according to the risk ratio. The 8-week overall survival rates of the low-risk group (82 cases), medium-risk group (36 cases), and high-risk group (21 cases) were 85.4%, 52.8%, and 23.8%, respectively (P < 0.001). Conclusions The early death of sHLH patients is closely related to some laboratory examination results. Attention should be paid to identify high-risk patients, choose effective first-line induction therapy, achieve deep remission as soon as possible, prevent deep organ bleeding, correct electrolyte disorders, and improve the early survival rate of sHLH patients.

Retrospective study of EGFR-mutant lung adenocarcinoma with bone metastatic clinical features.

With more and more target medicine application in lung cancer, lots of patients take medicine at home, the treatment bone metastasis and screen of bone metastasis always has been neglected until skeletal-related events (SREs) such as bone pain, hypercalcemia of malignancy and pathologic fractures emerging which significantly impairs the patients' daily activity ability, seriously lower quality of life. To identify the clinical characteristics of patients which influence the overall survival (OS) of EGFR-TKIs effective in EGFR-mutant NSCLC with bone metastasis (BM) and the bone metastatic image features. We conducted a retrospective study in patients (treated with EGFR-TKIs ≥6 months) of lung adenocarcinoma with BM in our hospital from October 2014 to October 2017. The Kaplan-Meier survival curves were calculated using the log-rank univariate test. Multivariate regression analysis was conducted using Cox's regression model. Comparison between the different subgroups of bone metastasis was conducted using Pearson Chi-Square test. A total of 79 patients were diagnosed as EGFR-mutant lung adenocarcinoma with bone metastases. At univariate analysis, age < 65 years (p = .024), heavy smoking (p = .005), Osteolytic BM (p = .034), number of bone metastasis ≥3 (p = .032), EGFR-L858R mutated (p = .018) and bisphosphonate times <6 (p = .046), were significantly associated with worse overall survival (OS). At multivariate analysis, EGFR 19del was an independent predictor of better OS (p = .035). Osteolytic BM was more likely to occur in EGFR-mutant patients (osteolytic vs. sclerotic vs. mixed: 45.57% vs. 34.18% vs. 20.25%). Patients who had received bisphosphonate ≥6 times were less suffer from SRE compared to those treated with bisphosphonate <6 times (p = .019). In conclusions, this retrospective study suggests that for the patients, treated with EGFR-TKIs ≥6months, EGFR exon 19 del, osteogenic bone metastasis, bisphosphonate application times ≥6, smoking <400/day and the number of BM <3 were predictors of better OS (p < .05). Bisphosphonate times ≥9 should be considered to the patients with BM. SPECT-CT would be an effective correction of SPECT in the patient's bone metastasis examination. During the whole follow-up process, we found by chance that the change of bone mineral density in the follow-up process suggested that bisphosphonates need to be used for more than 1 year or more, and we can use local CT in the follow-up clinical practice to confirm the bone density changes to decide when we could stop or reduce bisphosphonate application.

Clinical Characteristics in the Prediction of Posttreatment Survival of Patients with Ovarian Cancer.

Objective To determine the efficacy of clinical characteristics in the prediction of prognosis in patients with ovarian cancer. Methods Clinical data were collected from 3 datasets from TCGA database, including 1680 cases of ovarian serous cystadenocarcinoma, and were analyzed. Patients with ovarian cancer admitted to our hospital in 2016 were retrieved and followed up for prognosis analysis. Results From the datasets, for patients > 75 years old at the time of diagnosis, histologic grade and mutation count were good predictors for disease-free survival, while for patients > 50 years old at the time of diagnosis, histologic grade, race, fraction genome altered, and mutation count were good predictors for overall survival. In the patients (n = 38) retrieved from our hospital, the longest dimension of lesion (cm) and body weight at admission were good predictors for overall survival. Conclusions Those clinical factors, together with the two predictive equations, could be used to comprehensively predict the long-term prognosis of patients with ovarian cancer.

The evolution of clinical outcomes in metastatic pancreatic adenocarcinoma: a 10-year experience at a tertiary referral center

ABSTRACT Background Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer mortality in the US. Recent studies have demonstrated survival benefits for FOLFIRINOX (5-FU, leucovorin, irinotecan, and oxaliplatin) and Gem/nab-P (gemcitabine/nab-paclitaxel) over gemcitabine. We aimed to evaluate the clinical outcomes of mPDAC before and after incorporating these newer regimens into the clinical practice. Methods A retrospective study of patients with mPDAC at our institution between 2009 and 2018, who were followed up until December 2019. Overall survival (OS) and progression-free survival (PFS) were calculated using Kaplan–Meier survival analysis. Univariate and multivariable Cox regression analyses were used to explore predictors of survival. Results A total of 394 patients with mPDAC were included: 122 (31%) were diagnosed 2009-2013 and 272 (69%) 2014-2018. In 2009–2013 cohort vs. 2014–2018 cohort, the median OS and PFS were similar (4 vs. 3.6 months, P = 0.5) and (2.3 vs. 2.5 months, P = 0.41), respectively. Age, ECOG-PS >1, serum albumin, neutrophil-to-lymphocyte ratio, and platelets-to-lymphocyte ratio were independent predictors of better OS. Conclusions In this study of real-world data, the median OS and PFS for all patients with mPDAC were equivalent before and after incorporating newer treatment regimens into the clinical practice.

Inducible Co-Stimulator ICOS Expression Correlates with Immune Cell Infiltration and Can Predict Prognosis in Lung Adenocarcinoma.

BackgroundInducible co-stimulator (ICOS) is a cell-enhanced co-stimulatory receptor that has shown great potential in the regulation of innate and adaptive immunity. However, the role of ICOS in lung adenocarcinoma (LUAD) remains unclear.MethodsWe used data from the Cancer Genome Atlas(TCGA) database to identify the expression and prognostic role of ICOS in LUAD. The results were validated using Gene Expression Omnibus(GEO) and Kaplan-Meier plotter databases. A model with predictive performance for overall survival of LUAD patients was constructed using fitted ICOS expression and other clinical parameters. We explored the biological function of ICOS. Subsequently, we further analysed and validated the effect of ICOS expression on tumour immune microenvironment (TIME) and survival. Finally, the CellMiner database was used to determine the relationship between ICOS expression and drug sensitivity.ResultsICOS expression is significantly associated with poor prognosis in multiple cancers, especially LUAD, and is a good predictor of overall survival in LUAD patients. The biological function is to promote autoimmunity and inhibit cell proliferation. ICOS-related survival prediction model developed to more accurately predict 1-, 3- and 5-year survival probabilities for LUAD patients. In addition, we can use the expression of ICOS to effectively assess patient malignancy, prognosis, TIME status and clinical combination of drugs.ConclusionOur results suggest that ICOS is correlated with prognosis and immune infiltrating levels in LUAD. Higher ICOS expression predicts better TIME. This study provides a novel strategy for the development of immunotherapeutic and prognostic markers in LUAD.

The short-term and oncologic outcomes of younger VS older colorectal cancer patients undergoing primary surgery: a propensity score matching analysis

PurposeThe purpose of the current study is to analyze the difference of short-term and oncologic outcomes between younger and older colorectal cancer (CRC) patients who underwent primary CRC surgery using a propensity score matching (PSM) analysis.MethodsWe retrospectively collected CRC patients who underwent primary surgery in a single clinical database from Jan 2011 to Jan 2020. The short-term and oncologic outcomes were compared between younger aged group and older aged group.ResultsA total of 4599 patients were included in this study, and there were 4196 patients in older aged group and 403 patients in younger aged group. After 1:1 ratio PSM, there were 401 patients in each group. No significant difference was found in terms of baseline information after PSM (p>0.05). Younger aged group had larger retrieved lymph nodes before (p<0.001) and after PSM (p=0.001) than older aged group. In multivariate analysis, younger age was an independent predictor of better overall survival (OS) (p<0.001, HR=2.303, 95% CI=1.658-3.199) and disease-free survival (DFS) (p=0.008, HR=1.425, 95% CI=1.098-1.850). In terms of different tumor stage after PSM, younger aged group had better OS than older group in stage II (p<0.001) and stage IV (p=0.028) CRC, and younger aged group had better DFS than older group in stage II (p=0.016) CRC.ConclusionYounger CRC patients had larger retrieved lymph nodes and better prognosis than older CRC patients after primary CRC surgery.

Metastasectomy in colorectal cancer patients with concurrent lung and liver metastasis: Trends in utilization and impact on survival.

53 Background: Colorectal cancer (CRC) frequently presents with concurrent metastasis to the lung and liver. Metastasectomy may offer extended disease control in a select group of patients but its utilization is unknown. We aimed to investigate the trends in utilization of metastasectomy in CRC patients with concurrent lung and liver metastasis and explore its impact on survival. Methods: We queried the National Cancer Database and identified stage 4 CRC patients with concurrent lung and liver metastasis between 2010 – 2016 and categorized them into those that underwent metastasectomy vs. those that did not. Categorical variables were compared using the chi-square test, and statistically significant factors were included in multivariable logistic regression analysis. In addition, 1:2 propensity score matching was performed, and a multivariable Cox regression model was used to define survival predictors among matched cohorts. The Kaplan-Meier method was used to estimate the median survival. Results: Out of total 77,719 stage 4 CRC patients, 10,106 (13.0%) patients had concurrent lung and liver metastasis. Six percent (n = 630) of these patients underwent metastasectomy of both sites. Patients that underwent metastasectomy were more likely to be younger (&lt; 50 years; p = 0.009), female ( p &lt; 0.001), and White ( p = 0.01). These patients were also more likely to have right-sided CRC ( p = 0.001) and had resection of the primary site (p &lt; 0.001). Additionally, they were more likely to have private health insurance ( p &lt; 0.001) and receive treatment at an academic center ( p = 0.03). On adjusted multivariable analysis, female gender, care at an academic center, primary tumor resection and receiving chemotherapy were associated with the metastasectomy group. We did not find a statistically significant difference between comorbidity score, KRAS status and microsatellite status between the 2 groups. In the matched analysis, overall survival (OS) was significantly improved for patients who underwent metastasectomy (23.2 months) vs. those who did not (11.6 months, p &lt; 0.001). On multivariable analysis, this difference remained, and metastasectomy was an independent predictor of better OS (HR 0.74 [0.65-0.85], p &lt; 0.001). Conclusions: The utilization of metastasectomy in concurrent lung and liver metastasis is low. It is more frequently used in younger, female and White patients, as well as in patients treated at an academic center. Metastasectomy is independently associated with improved overall survival in patients eligible for such an approach.

The role of liver resection in metastatic nephroblastoma: a systematic review and Meta-regression analysis

BackgroundThe impact of hepatic resection for liver metastases (LM) on the survival of pediatric patients with Wilms’ tumor (WT) is unclear. So far, there is a lack of studies investigating the best suited treatment for patients with WTLM, and the role of liver resection has rarely been investigated. Thus, the development of evidence-based guidelines concerning indications of liver resection for WTLM remains difficult.AimTo investigate the role of surgery in the therapy of WTLM. All available data on liver resections and subgroup outcomes of patients with WTLM are analyzed. Main research question is whether liver resection improves survival rates of patients with WTLM compared to non-surgical treatment.MethodsA systematic literature search of MEDLINE, Web of Science, and Central provided the basis for this PRISMA-compliant systematic review. For the main analysis (I), all studies reporting on surgical treatment of pediatric WTLM were included. To provide a representative overview of the general outcome of WTLM patients, in analysis II all studies with cohorts of at least five WTLM patients, regardless of the kind of treatment, were reviewed and analyzed. A Multiple meta-regression model was applied to investigate the impact liver resection on overall survival.Results14 studies with reports of liver resection for WTLM were found (Analysis I). They included a total of 212 patients with WTLM, of which 93 underwent a liver resection. Most studies had a high risk of bias, and the quality was heterogenous. For the analysis II, eight studies with subgroups of at least five WTLM patients were found. The weighted mean overall survival (OS) of WTLM patients across the studies was 55% (SD 29). A higher rate of liver resection was a significant predictor of better OS in a multiple meta-regression model with 4 covariates (I2 29.43, coefficient 0.819, p = 0.038).ConclusionsThis is the first systematic review on WTLM. Given a lack of suited studies that specifically investigated WTLM, ecological bias was high in our analyses. Generating evidence is complicated in rare pediatric conditions and this study must be viewed in this context. Meta-regression analyses suggest that liver resection may improve survival of patients with WTLM compared to non-surgical treatment. Especially patients with persisting disease after neoadjuvant chemotherapy but also patients with metachronous LM seem to benefit from resection. Complete resection of LM is vital to achieve higher OS. Studies that prospectively investigate the impact of surgery on survival compared to non-surgical treatment for WTLM are highly needed to further close the current evidence gap.Study RegistrationPROSPERO 2021 CRD42021249763 https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=249763.

The obesity paradox and mortality after pathological hip fractures: a Swedish registry study.

Background and purposeObesity as measured by BMI has been associated with increased survival in various diseases, a phenomenon known as the “obesity paradox.” It is unknown whether obesity is associated with survival after pathological fractures. We investigated the association between BMI and survival after surgery for pathological hip fracture, to improve survival prognostication, and lay grounds for further interventional nutritional studies.Patients and methodsWe analyzed prospectively collected data from Swedish nationwide registry “RIKSHÖFT.” The study cohort included 1,000 patients operated for a pathological hip fracture between 2014 and 2019. BMI registered on admission was available in 449 patients. Overall patient survival was measured according to the Kaplan– Meier method. Multivariable regression was used to evaluate association with other potential factors that influence patient survival.ResultsOverweight and obesity were associated with an increased postoperative survival in male patients with surgically treated pathological hip fractures. Multivariable analysis considering potential confounders confirmed this finding. The association was not that strong in women and did not reach statistical significance.InterpretationBMI, a commonly available clinical parameter, is a good predictor of overall survival for patients operated on for pathological hip fracture. Incorporation of BMI in existent survival prognostication algorithms should be considered. Treatment of malnutrition in this frail group of patients is worth studying.

Intratumoral Heterogeneity and Immune Response Indicators to Predict Overall Survival in a Retrospective Study of HER2-Borderline (IHC 2+) Breast Cancer Patients.

Breast cancer (BC) categorized as human epidermal growth factor receptor 2 (HER2) borderline [2+ by immunohistochemistry (IHC 2+)] presents challenges for the testing, frequently obscured by intratumoral heterogeneity (ITH). This leads to difficulties in therapy decisions. We aimed to establish prognostic models of overall survival (OS) of these patients, which take into account spatial aspects of ITH and tumor microenvironment by using hexagonal tiling analytics of digital image analysis (DIA). In particular, we assessed the prognostic value of Immunogradient indicators at the tumor–stroma interface zone (IZ) as a feature of antitumor immune response. Surgical excision samples stained for estrogen receptor (ER), progesterone receptor (PR), Ki67, HER2, and CD8 from 275 patients with HER2 IHC 2+ invasive ductal BC were used in the study. DIA outputs were subsampled by HexT for ITH quantification and tumor microenvironment extraction for Immunogradient indicators. Multiple Cox regression revealed HER2 membrane completeness (HER2 MC) (HR: 0.18, p = 0.0007), its spatial entropy (HR: 0.37, p = 0.0341), and ER contrast (HR: 0.21, p = 0.0449) as independent predictors of better OS, with worse OS predicted by pT status (HR: 6.04, p = 0.0014) in the HER2 non-amplified patients. In the HER2-amplified patients, HER2 MC contrast (HR: 0.35, p = 0.0367) and CEP17 copy number (HR: 0.19, p = 0.0035) were independent predictors of better OS along with worse OS predicted by pN status (HR: 4.75, p = 0.0018). In the non-amplified tumors, three Immunogradient indicators provided the independent prognostic value: CD8 density in the tumor aspect of the IZ and CD8 center of mass were associated with better OS (HR: 0.23, p = 0.0079 and 0.14, p = 0.0014, respectively), and CD8 density variance along the tumor edge predicted worse OS (HR: 9.45, p = 0.0002). Combining these three computational indicators of the CD8 cell spatial distribution within the tumor microenvironment augmented prognostic stratification of the patients. In the HER2-amplified group, CD8 cell density in the tumor aspect of the IZ was the only independent immune response feature to predict better OS (HR: 0.22, p = 0.0047). In conclusion, we present novel prognostic models, based on computational ITH and Immunogradient indicators of the IHC biomarkers, in HER2 IHC 2+ BC patients.

Tumor enhancement ratio with unenhanced imaging is an independent prognostic factor for patients with hepatocellular carcinoma after transarterial chemoembolization.

ObjectiveTo investigative whether the odds tumor enhancement ratio (OTER) on cross-sectional imaging is a prognostic factor for hepatocellular carcinoma after transarterial chemoembolization (TACE).MethodsThis study involved 126 patients who underwent TACE from May 2015 to March 2019. The signal intensity/Hounsfield units (HU) was measured by placing regions of interest on the tumor and surrounding liver in unenhanced and arterial-phase contrast-enhanced cross-sectional images. The OTER was calculated as follows: OTER = (HUTUMORart − HUTUMORun)/ (HULIVERart − HULIVERun). Univariate analysis was performed to determine the factors associated with overall survival (OS). Variables with a P value of <0.10 were included in the multivariate Cox regression analysis.ResultsThe median OS was 757 days. Tumors with a peripheral location, small size, and low OTER had better OS than those with a central location, large size, and high OTER. OS did not differ according to the extent of tumor involvement or tumor enhancement pattern. The OTER, tumor location, and size were included in the multivariate Cox regression analysis. A low OTER was the predictor of better OS.ConclusionA high OTER is a risk factor for poor OS in patients undergoing TACE. This should be taken into consideration before the procedure.

Predictive value of red blood cell distribution width level on histological response and prognosis in colorectal liver metastases.

The red blood cell distribution width (RDW) level is a potential prognostic factor for solid tumours. We aimed to investigate the predictive value of pre-neoadjuvant chemotherapy (pre-NAC) RDW, preoperative RDW and the change in RDW on the pathological response and prognosis of patients with colorectal liver metastasis (CRLM), which was helpful for treatment decision-making, surveillance and prognostication. This retrospective study analyzed clinicopathologic data, treatments and outcomes of 150 CRLM patients treated with NAC followed by liver resection at our hospital. The primary outcomes were progression-free survival (PFS) and overall survival (OS). The secondary outcome was postoperative major complications. The RDW level was presented as the RDW-SD level and the RDW-CV level. The optimal cut-off of RDW level was determined by X-tile analysis. The change in RDW was scored as 0 (decreased pre-NAC RDW and decreased preoperative RDW), 2 (elevated pre-NAC RDW and elevated preoperative RDW), or 1 (all other combinations). Multivariable logistic regression analysis was performed to determine the relationships between the tumour characteristics and pathological response and the postoperative major complications. A multivariate Cox proportional hazards model was used to evaluate the prognostic factors associated with survival. The optimal cut-off values of the RDW-CV and RDW-SD levels for survival were 13.5% and 42.2 fl, respectively. The multivariate analysis showed that a preoperative RDW-CV ≥13.5% (OR =3.215, 95% CI: 1.299-7.958, P=0.012) significantly predicted a favorable pathological response. The multivariate analysis revealed that a pre-NAC RDW-CV ≥13.5% (OR =2.462, 95% CI: 1.080-5.615, P=0.032) significantly predicted postoperative major complications. In the multivariate analysis, an RDW-CV change =2 (HR =0.487, 95% CI: 0.309-0.768, P=0.002) was a significant predictor of better PFS. The multivariate analysis also revealed that an RDW-SD change =2 (HR =0.532, 95% CI: 0.332-0.854, P=0.009) were an independent predictor of better OS. This study revealed that pre-NAC RDW, preoperative RDW and RDW changes may be reliable markers that could predict a pathological response and prognosis in CRLM patients receiving NAC followed by liver resection.