Breast cancer survival in India across 11 geographic areas under the National Cancer Registry Programme.

BACKGROUND: Population-based cancer survival is a key indicator for assessing the effectiveness of cancer control by a health care system in a specific geographic area. Breast cancer is the most common cancer among women in India, accounting for over one quarter of all female cancers. The objective of this study was to estimate the 5-year survival of female patients who were diagnosed with breast cancer between 2012 and 2015 from the existing Population-Based Cancer Registries (PBCRs) in India. METHODS: In total, 17,331 patients who had breast cancer diagnosed between 2012 and 2015 from 11 PBCRs were followed until June 30, 2021. Active methods were used to track the vital status of registered breast cancer cases. The study conducted survival analysis by calculating the difference between the date of first diagnosis and the date of death or censoring to estimate observed survival and relative survival using the actuarial survival approach and the Ederer-II approach, respectively. RESULTS: The 5-year age-standardized relative survival (95% confidence interval [CI]) of patients with breast cancer was 66.4% (95% CI, 65.5%-67.3%). Mizoram (74.9%; 95% CI, 68.1%-80.8%), Ahmedabad urban (72.7%; 95% CI, 70.3%-74.9%), Kollam (71.5%; 95% CI, 69.2%-73.6%), and Thiruvananthapuram (69.1%; 95% CI, 67.0%-71.2%) had higher survival rates than the national average. Conversely, Pasighat had the lowest survival rate (41.9%; 95% CI, 14.7%-68.6%). The 5-year observed survival rates for localized, regional, and distant metastasis in the pooled PBCRs were 81.0%, 65.5%, and 18.3%, respectively. CONCLUSIONS: The overall disparity in survival rates was observed across 11 PBCRs, with lower survival rates reported in Manipur, Tripura, and Pasighat. Therefore, it is imperative to implement comprehensive cancer control strategies widely throughout the country.

Value of Adherence to Posttreatment Follow-Up Guidelines for Head and Neck Squamous Cell Carcinoma.

OBJECTIVES: The utility of intensive posttreatment surveillance of head and neck squamous cell carcinoma (HNSCC) has been debated. The objective is to investigate adherence to the National Comprehensive Cancer Network (NCCN) posttreatment follow-up guidelines and assess the association with recurrence and survival. METHODS: A total of 452 patients diagnosed with HNSCC at an academic medical center in a socioeconomically disadvantaged, urban setting were categorized by adherence to NCCN follow-up guidelines. Survival analyses were conducted to study the association between adherence and the 5-year overall survival and disease-specific survival in the entire cohort and subset of patients with documented recurrence. RESULTS: We found that 23.5% of patients were adherent to NCCN follow-up guidelines in the first year after treatment, and 15.9% were adherent over 5 years. Adherence in the first year was significantly associated with 5-year overall survival (HR 0.634; 95% CI 0.443-0.906; p = 0.0124) and disease-specific survival (HR 0.556; 95% CI 0.312-0.992; p = 0.0470), but consistent adherence over 5 years did not show a significant association. Among the 21.7% of the cohort with recurrence, adherence was not associated with early-stage recurrence (AJCC stage I/II). In this subset, first year adherence was associated with improved disease-specific but not overall survival, and adherence over 5 years was not associated with survival. CONCLUSION: Adherence to NCCN follow-up guidelines in the first year after treatment was associated with a better chance of 5-year overall and disease-specific survival, but this significant association was not observed among those who demonstrated consistent adherence over 5 years. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:708-716, 2024.

Tumor Marker Trajectories and Survival Analysis in Patients With Normal Carcinoembryonic Antigen Ranges After Colorectal Cancer Resection.

BACKGROUND: Evidence regarding postoperative CEA for predicting long-term outcomes of colorectal cancer remains controversial, especially in patients with normal postoperative CEA. OBJECTIVE: To investigate the risk difference among different postoperative CEA trajectories in patients with normal postoperative CEA after curative colorectal cancer resection. DESIGN: This cohort study was conducted at a comprehensive cancer center and included data retrieved from a prospectively collected database between January 2006 and December 2018. SETTINGS: Retrospective cohort study. PATIENTS: Patients with colorectal cancer who underwent surgery for primary stage I to III colorectal adenocarcinoma were included and those with postoperative CEA >5 ng/mL were excluded. INTERVENTIONS: Standard curative radical resection was performed. MAIN OUTCOME MEASURES: Ten-year overall survival and disease-free survival were analyzed. RESULTS: The study population (n = 8156) was categorized into 6 trajectories: persistent-ultralow (n = 2351), persistent-low (n = 2474), gradually decrease (n = 401), persistent-medium (n = 1727), slightly increase (n = 909), and around-upper-limit (n = 394). The median follow-up time was 7.8 years, and the median time frame in which CEA was measured to determine trajectory was 2.6 years. The persistent-ultralow group had the highest 10-year overall survival (85.1%) and disease-free survival (82.7%). The around-upper-limit group had the lowest 10-year overall survival (55.5%) and disease-free survival (53.4%). The adjusted HR trend was comparable to the crude HR of the persistent-ultralow group. Consequently, the higher initial serum CEA groups had higher HRs of overall survival and disease-free survival. The adjusted HR of overall survival was 2.96 (95% CI, 2.39-3.66) and of disease-free survival was 2.66 (95% CI, 2.18-3.69) for the around-upper-limit groups. LIMITATIONS: Retrospective design. CONCLUSIONS: The postoperative serum CEA trajectory is an independent factor associated with long-term outcomes. Although CEA levels were all within normal range, higher levels of postoperative serum CEA trajectory correlated with worse long-term oncological outcomes. See Video Abstract. TRAYECTORIAS DE MARCADORES TUMORALES Y ANLISIS DE SUPERVIVENCIA EN PACIENTES CON RANGOS NORMALES DE ANTGENO CARCINOEMBRIONARIO POSTERIOR A RESECCIN DE CNCER COLORRECTAL: ANTECEDENTES:La evidencia sobre el CEA post operatorio para la predicción de los resultados a largo plazo del cáncer colorrectal sigue siendo controversial, especialmente en pacientes con CEA post quirúrgico normal.OBJETIVO:Investigar la diferencia de riesgo entre diferentes trayectorias postoperatorias del CEA en pacientes con CEA post quirúrgico normal tras la resección curativa del cáncer colorrectal.DISEÑO:Este estudio de cohorte se realizó en un centro oncológico integral e incluyó datos recuperados de una base de datos recopilada prospectivamente entre enero de 2006 y diciembre de 2018.AJUSTES:Estudio de cohorte retrospectivo.PACIENTES:Se incluyeron pacientes con el diagnostico de CCR que fueron sometidos a cirugía por adenocarcinoma colorrectal primario en estadio I-III. Se excluyeron pacientes con CEA postoperatorio >5 ng/mL.INTERVENCIONES:Se realizó una resección radical curativa estandarizada.PRINCIPALES MEDIDAS DE RESULTADO:Se analizaron la supervivencia general a diez años y la supervivencia libre de enfermedad.RESULTADOS:La población de estudio (n = 8156) fue clasificada en seis trayectorias, que incluyeron ultrabajo persistente (n = 2351), bajo persistente (n = 2474), disminución gradual (n = 401), medio persistente (n = 1727), aumento leve (n = 909) y alrededor del límite superior (n = 394). La mediana del tiempo de seguimiento fue de 7,8 años y la mediana del período de tiempo en el que el CEA fue medido para determinar la trayectoria fue de 2,6 años. El grupo ultrabajo persistente tuvo la mayor supervivencia general a 10 años (85,1 %) y supervivencia libre de enfermedad (82,7 %). El grupo alrededor del límite superior tuvo la supervivencia general a 10 años más baja (55,5 %) y la supervivencia libre de enfermedad (53,4 %). La tendencia del índice de riesgo ajustado fue comparable al índice de riesgo bruto del grupo ultrabajo persistente. En consecuencia, los grupos con CEA sérico iniciales más altos tenían índices de riesgos más altos de supervivencia general y supervivencia libre de enfermedad. Los índices de riesgos ajustados de supervivencia general/supervivencia libre de enfermedad fueron 2,96/2,66 (intervalo de confianza del 95 %: 2,39-3,66/2,18-3,69) para los grupos cercanos al límite superior.LIMITACIONES:El estudio estuvo limitado por su diseño retrospectivo.CONCLUSIONES:La trayectoria del CEA sérico postoperatorio es un factor independiente asociado con resultados a largo plazo. Aunque los niveles de CEA se encontraban todos dentro del rango normal, los niveles más altos de trayectoria del CEA en suero posoperatorio se correlacionaron con peores resultados oncológicos a largo plazo. (Traducción-Dr Osvaldo Gauto ).

Survival with chronic myeloid leukaemia after failing milestones.

Therapy after failing response milestones in CML is controversial. Risks associated with comorbidities, drug toxicities or transplantation may preclude switching to another tyrosine kinase inhibitor (TKI) or other treatments. No information on long-term survival of failing patients is available. To systematically analyse survival after reaching, or not reaching, response milestones, 1342 patients from CML-study IV with newly diagnosed CML in chronic phase and regular molecular tests were studied. Landmark survival analyses were done by <0.1%, 0.1-1%, >1-10% and >10% BCR::ABL1IS at 3, 6, 12 and 24 months up to 14 years. 10- to 12-year survival of patients who failed the failure milestones (>10% BCR::ABL1IS at 6 months, >1% BCR::ABL1IS at 12 months) ranged around 80%, 10% less than in responding patients. These results suggest revision of milestones. Age (more or less than 60 years) had no major impact on survival differences, but on hazard ratios and CML-specific survival. Switching to alternative therapies, which was observed in 26.9% of the patients, did not change the main results. The data show that TKI-treated patients not reaching failure milestones still may derive benefit from continuing TKI-treatment and provide a basis for individualised decisions, if failing patients are confronted with risks of alternative treatments.

Cancer-specific survival in non-mucinous appendiceal adenocarcinomas after local resection versus right hemicolectomy: A Surveillance, Epidemiology, and End Results database study.

BACKGROUND: Adenocarcinomas of the appendix are rare cancers for which no National Comprehensive Cancer Network guidelines exist, and for patients who undergo resection with curative intent, there is a paucity of data on prognostic factors affecting long-term cancer-specific survival. We aimed to compare the cancer-specific survival outcomes in adult patients with appendiceal non-mucinous adenocarcinoma undergoing either local resection versus right hemicolectomy. METHODS: This was a retrospective study from the National Cancer Institute Surveillance, Epidemiology, and End Results of patients who underwent curative resection over a 15-year period (2004-2019) for primary appendiceal adenocarcinoma. Out of 16,699 patients, 14,945 were excluded (exclusion criteria were non-adenocarcinoma histological types and patients with regional or distant metastasis as per National Cancer Institute Surveillance, Epidemiology, and End Results stage). Effects of factors (age, race, tumor biology [mucinous versus non-mucinous tumors], the extent of resection of the primary lesion, and lymph nodes) on cancer-specific long-term survival were studied. Survival analysis was performed using the Kaplan-Meier method. Survival outcomes were reported as mean survival (months). RESULTS: Of 1,754 patients, 827 (47.1%) were women, and 927 (52.1%) were men. The mean age in years (± standard deviation) was 62.43 ± 14.3. The racial distribution was as follows: Black 237 (13.5%), White 1,398 (79.7%), and Other 119 (6.8%). A total of 771 (44.6%) underwent local resection (appendectomy or segmental resection of colon without lymph node resection), and 983 (55.4%) underwent hemicolectomy with lymph node resection. Favorable survival prognosticators were age <50 years, White race, and well-differentiated histology. Patients with mucinous tumors experienced better survival. Patients who underwent right hemicolectomy with lymph node resection experienced better survival compared with those who had an appendectomy or segmental colonic resection for non-mucinous tumors rather than mucinous tumors. CONCLUSION: We report novel demographic, tumor-related, and operative prognostic factors impacting long-term cancer-specific survival in patients who undergo resection for appendiceal adenocarcinoma. The extent of resection of the primary lesion with draining lymph nodes determines long-term cancer-specific survival in non-mucinous appendiceal adenocarcinomas.

Perioperative Nivolumab and Chemotherapy in Stage III Non-Small-Cell Lung Cancer.

BACKGROUND: Approximately 20% of patients with non-small-cell lung cancer (NSCLC) receive a diagnosis of stage III disease. There is no current consensus regarding the most appropriate treatment for these patients. METHODS: In this open-label, phase 2 trial, we randomly assigned patients with resectable stage IIIA or IIIB NSCLC to receive neoadjuvant nivolumab plus platinum-based chemotherapy (experimental group) or chemotherapy alone (control group), followed by surgery. Patients in the experimental group who had R0 resections received adjuvant treatment with nivolumab for 6 months. The primary end point was a pathological complete response (0% viable tumor in resected lung and lymph nodes). Secondary end points included progression-free survival and overall survival at 24 months and safety. RESULTS: A total of 86 patients underwent randomization; 57 were assigned to the experimental group and 29 were assigned to the control group. A pathological complete response occurred in 37% of the patients in the experimental group and in 7% in the control group (relative risk, 5.34; 95% confidence interval [CI], 1.34 to 21.23; P = 0.02). Surgery was performed in 93% of the patients in the experimental group and in 69% in the control group (relative risk, 1.35; 95% CI, 1.05 to 1.74). Kaplan-Meier estimates of progression-free survival at 24 months were 67.2% in the experimental group and 40.9% in the control group (hazard ratio for disease progression, disease recurrence, or death, 0.47; 95% CI, 0.25 to 0.88). Kaplan-Meier estimates of overall survival at 24 months were 85.0% in the experimental group and 63.6% in the control group (hazard ratio for death, 0.43; 95% CI, 0.19 to 0.98). Grade 3 or 4 adverse events occurred in 11 patients in the experimental group (19%; some patients had events of both grades) and 3 patients in the control group (10%). CONCLUSIONS: In patients with resectable stage IIIA or IIIB NSCLC, perioperative treatment with nivolumab plus chemotherapy resulted in a higher percentage of patients with a pathological complete response and longer survival than chemotherapy alone. (Funded by Bristol Myers Squibb and others; NADIM II ClinicalTrials.gov number, NCT03838159; EudraCT number, 2018-004515-45.).

Orychophragine D:A new 2-piperazinone fused 5-azacytosine type alkaloid with radioprotective activity from the seeds of Orychophragmus violaceus.

A new alkaloid, Orychophragine D (1), together with three known alkaloids, were isolated from the seeds of Orychophragmus violaceus. Orychophragine D represented the first example of 2-piperazinone fused 5-azacytosine skeleton. Their structures and absolute configurations were determined by spectroscopic analyses and X-ray crystallography. Compared to Ex-RAD, compound 1 exhibited a significant radioprotective activity on cell survival of irradiated HUVEC. In vivo experiments showed that 1 not only remarkably enhanced the survival of irradiated mice in 30 days, but also significantly promoted the recovery of the blood system of irradiated mice. These results suggested that 1 was valuable for further research as promising radioprotectors.

Racial and socioeconomic disparities in glioblastoma outcomes: A single-center, retrospective cohort study.

BACKGROUND: Glioblastoma (GBM) is the most common malignant primary brain tumor. Emerging reports have suggested that racial and socioeconomic disparities influence the outcomes of patients with GBM. No studies to date have investigated these disparities controlling for isocitrate dehydrogenase (IDH) mutation and O-6-methylguanine-DNA methyltransferase (MGMT) status. METHODS: Adult patients with GBM were retrospectively reviewed at a single institution from 2008 to 2019. Univariable and multivariable complete survival analyses were performed. A Cox proportional hazards model was used to assess the effect of race and socioeconomic status controlling for a priori selected variables with known relevance to survival. RESULTS: In total, 995 patients met inclusion criteria. Of these, 117 patients (11.7%) were African American (AA). The median overall survival for the entire cohort was 14.23 months. In the multivariable model, AA patients had better survival compared with White patients (hazard ratio [HR], 0.37; 95% confidence interval [CI], 0.2-0.69). The observed survival difference was significant in both a complete case analysis model and a multiple imputations model accounting for missing molecular data and controlling for treatment and socioeconomic status. AA patients with low income (HR, 2.17; 95% CI, 1.04-4.50), public insurance (HR, 2.25; 95% CI, 1.04-4.87), or no insurance (HR, 15.63; 95% CI, 2.72-89.67) had worse survival compared with White patients with low income, public insurance, or no insurance, respectively. CONCLUSIONS: Significant racial and socioeconomic disparities were identified after controlling for treatment, GBM genetic profile, and other variables associated with survival. Overall, AA patients demonstrated better survival. These findings may suggest the possibility of a protective genetic advantage in AA patients. PLAIN LANGUAGE SUMMARY: To best personalize treatment for and understand the causes of glioblastoma, racial and socioeconomic influences must be examined. The authors report their experience at the O'Neal Comprehensive Cancer Center in the deep south. In this report, contemporary molecular diagnostic data are included. The authors conclude that there are significant racial and socioeconomic disparities that influence glioblastoma outcome and that African American patients do better.

Pharmacological ascorbate induces sustained mitochondrial dysfunction.

Pharmacological ascorbate (P-AscH-; high dose given intravenously) generates H2O2 that is selectively cytotoxic to cancer compared to normal cells. The RAS-RAF-ERK1/2 is a major signaling pathway in cancers carrying RAS mutations and is known to be activated by H2O2. Activated ERK1/2 also phosphorylates the GTPase dynamin-related protein (Drp1), which then stimulates mitochondrial fission. Although early generation of H2O2 leads to cytotoxicity of cancer cells, we hypothesized that sustained increases in H2O2 activate ERK-Drp1 signaling, leading to an adaptive response; inhibition of this pathway would enhance the toxicity of P-AscH-. Increases in phosphorylated ERK and Drp1 induced by P-AscH- were reversed with genetic and pharmacological inhibitors of ERK and Drp1, as well as in cells lacking functional mitochondria. P-AscH- increased Drp1 colocalization to mitochondria, decreased mitochondrial volume, increased disconnected components, and decreased mitochondrial length, suggesting an increase in mitochondrial fission 48 h after treatment with P-AscH-. P-AscH- decreased clonogenic survival; this was enhanced by genetic and pharmacological inhibition of both ERK and Drp1. In murine tumor xenografts, the combination of P-AscH- and pharmacological inhibition of Drp1 increased overall survival. These results suggest that P-AscH- induces sustained changes in mitochondria, through activation of the ERK/Drp1 signaling pathway, an adaptive response. Inhibition of this pathway enhanced the toxicity P-AscH- to cancer cells.

Survival Disparities in US Black Compared to White Women with Hormone Receptor Positive-HER2 Negative Breast Cancer.

Black women in the US have significantly higher breast cancer mortality than White women. Within biomarker-defined tumor subtypes, disparate outcomes seem to be limited to women with hormone receptor positive and HER2 negative (HR+/HER2-) breast cancer, a subtype usually associated with favorable prognosis. In this review, we present data from an array of studies that demonstrate significantly higher mortality in Black compared to White women with HR+/HER2-breast cancer and contrast these data to studies from integrated healthcare systems that failed to find survival differences. Then, we describe factors, both biological and non-biological, that may contribute to disparate survival in Black women.

Association between Tai Chi Yuttari Exercise and Longevity and Prevention of Long-Term Care Need: Survival Analysis in Kitakata City, Japan.

This study examined whether participation in Tai Chi Yuttari exercise is associated with a delay in the death and new certification for long-term care need of older adults. Individuals who participated in Tai Chi Yuttari exercise classes in 2011-2015 (participation group) were compared with individuals from the Basic Resident Register of Kitakata City (non-participation group). Death and new certification for long-term care need were selected to evaluate the effectiveness of participation in Tai Chi Yuttari exercise classes. The periods from the start date of the observation to each person's date of occurrence of events were calculated. The Kaplan-Meier method and log-rank test were used to compare survival curves between the groups. A total of 105 and 202 individuals in the participation and non-participation groups, respectively, were observed. Survival duration (χ2 = 8.782, p = 0.003) and the period before receiving certification for long-term care (χ2 = 5.354, p = 0.021) were longer in the participation group than in the non-participation group. In the stratified analysis by sex, survival duration was longer in the participation group in men only (χ2 = 7.875, p = 0.005). Participation in Tai Chi Yuttari exercise might be effective in delaying death, especially in men, and new certification for long-term care.

Outcomes in patients with pancreatic ductal adenocarcinoma (PDAC) undergoing robotic (RPD) or open pancreaticoduodenectomies (OPD): a propensity score-weighted survival analysis.

The purpose of this study was to compare the survival, recurrence, and complication rates in patients with pancreatic ductal adenocarcinoma (PDAC) who underwent robotic pancreaticoduodenectomy (RPD) or open pancreaticoduodenectomy (OPD) and who received adjuvant therapy. The study was a single-center retrospective analysis of consecutive PDAC patients who underwent RPD/OPD. Patient characteristics, tumor findings, neoadjuvant therapy, adjuvant therapies, overall survival (OS) and recurrence-free survival (RFS) were compared between the OPD and RPD cohorts. Cox proportional hazard regression with and without propensity score matching was used to establish the association between predictors and outcomes. One hundred PDAC patients underwent OPD (n = 36) or RPD (n = 64) from 2013 to 2019. Cox proportional hazard models showed that baseline bilirubin (HR 1.6, p = 0.0006) and operative characteristics such as the number of positive lymph nodes (HR 1.1, p = 0.002), lymph node ratio (HR 1.6, p = 0.001), tumor grade (HR 1.7, p = 0.02), and TNM classification (HR 2.3, p = 0.01) were associated with OS. The independent predictors post-intervention associated with mortality were adjuvant therapy (HR 0.4, p = 0.0003), ISGPS complications (HR 2.8, p = 0.02), and 90-day readmission (HR 2, p = 0.004). After adjustment for these predictors, adjuvant therapy, baseline bilirubin, lymph node ratio, and tumor grade remained the main predictors of mortality. Baseline bilirubin, adjuvant therapy, lymph node ratio, and tumor grade were the main determinants of mortality after OPD or RPD. There was no significant difference in OS and RFS after RPD or OPD in PC patients who received adjuvant therapy.

Overweight or obesity increases the risk of cardiovascular disease among older Australian adults, even in the absence of cardiometabolic risk factors: a Bayesian survival analysis from the Hunter Community Study.

OBJECTIVE: To estimate the risk of cardiovascular disease (CVD) in older adults with overweight or obesity without metabolic risk factors using a Bayesian survival analysis. DESIGN: Prospective cohort study with median follow-up of 9.7 years. SETTING: Newcastle, New South Wales, Australia. PARTICIPANTS: A total of 2313 community-dwelling older men and women. INTERVENTION/EXPOSURE: Participants without known CVD and with a body mass index (BMI) ≥ 18.5 kg m2 were stratified by BMI and metabolic risk to create six BMI-metabolic health categories. Metabolic risk was defined according to the International Diabetes Federation criteria for metabolic syndrome. 'Metabolically healthy' was defined as absence of metabolic risk factors. Bayesian survival analysis, incorporating prior information from a previously published meta-analysis was used to assess the effect of BMI-metabolic health categories on time from recruitment to CVD. MAIN OUTCOME: Incident physician-diagnosed CVD, defined as fatal or nonfatal myocardial infarction, fatal or nonfatal stroke, angina, or coronary revascularisation procedure, was determined by linkage to hospital admissions records and Medicare Australia data. Secondary outcomes were cardiovascular mortality and all-cause mortality. RESULTS: From 2313 adults with complete metabolic health data over a median follow-up of 9.7 years, 283 incident CVD events, 58 CVD related deaths and 277 deaths from any cause occurred. In an adjusted Bayesian survival model of complete cases with informative prior and metabolically healthy normal weight as the reference group, the risk of CVD was increased in metabolically healthy overweight (HR = 1.52, 95% credible interval 0.96-2.36), and in metabolically healthy obesity (HR = 1.86, 95% credible interval 1.14-3.08). Imputation of missing metabolic health and confounding data did not change the results. CONCLUSION: There was increased risk of CVD in older adults with overweight or obesity, even in the absence of any metabolic abnormality. This argues against the notion of 'metabolically healthy' overweight or obesity.

Effectiveness of herbal medicine on patients with amyotrophic lateral sclerosis: Analysis of the PRO-ACT data using propensity score matching.

BACKGROUND: Patients with amyotrophic lateral sclerosis (ALS) have restricted pharmacotherapy options and thus resort to herbal medicines (HMs), despite limited and conflicting evidence. Therefore, use of HMs needs to be assessed in patients with ALS. PURPOSE: This study aimed to evaluate the benefits of HMs in ALS and to describe the characteristics of HM users. STUDY DESIGN: The correlation between HMs and prognosis was determined based on data obtained from the largest ALS database with high-quality clinical trials. Propensity score (PS) matching was used to address confounding and selection bias. METHODS: In total, 321 and 231 HM users with at least a 4-week HM prescription were identified and PS-matched with non-HM users at a 1:1 ratio based on predefined confounders. Time-to-event models with censoring at 12 or 18 months were established for survival analyses. For evaluating activity limitation and respiratory function, 320 and 376 HM users were included, respectively, and analyzed using multivariate analysis of variance (MANOVA). RESULTS: The profiles of 321 HM users indicated a better condition compared with that of non-HM users before PS-matching, including higher weight (median [IQR], 77.90 [21.8] kg vs. 74.00 [21.2] kg, p < 0.01), higher body mass index (26.00 [5.4] vs. 25.20 [5.8], p < 0.01), more percentage of limb onset (261 [81.3%] vs. 2366 [67.2%], p < 0.01), and slower progression (0.47 [0.5] vs. 0.51 [0.5], p = 0.03). HM did not significantly affect survival at 12 months (adjusted hazard ratio [HR] 0.71, 95% confidence interval [CI] 0.49-1.03; log-rank p = 0.069), but it significantly prolonged survival at 18 months (adjusted HR 0.74, 95% CI 0.56-0.98; log-rank p = 0.038). After imputation of missing data, MANOVA revealed significant effectiveness of HMs in improving activity limitation (Pillai trace, 0.0195; p = 0.03). CONCLUSION: PS-based methods eliminated baseline differences between HM and non-HM users. Overall, the use of HM to treat patients with ALS is favored based on their association with prolonged overall survival within 18 months and improved activity limitation.

Survival analysis of localized prostate cancer with deep learning.

In recent years, data-driven, deep-learning-based models have shown great promise in medical risk prediction. By utilizing the large-scale Electronic Health Record data found in the U.S. Department of Veterans Affairs, the largest integrated healthcare system in the United States, we have developed an automated, personalized risk prediction model to support the clinical decision-making process for localized prostate cancer patients. This method combines the representative power of deep learning and the analytical interpretability of parametric regression models and can implement both time-dependent and static input data. To collect a comprehensive evaluation of model performances, we calculate time-dependent C-statistics [Formula: see text] over 2-, 5-, and 10-year time horizons using either a composite outcome or prostate cancer mortality as the target event. The composite outcome combines the Prostate-Specific Antigen (PSA) test, metastasis, and prostate cancer mortality. Our longitudinal model Recurrent Deep Survival Machine (RDSM) achieved [Formula: see text] 0.85 (0.83), 0.80 (0.83), and 0.76 (0.81), while the cross-sectional model Deep Survival Machine (DSM) attained [Formula: see text] 0.85 (0.82), 0.80 (0.82), and 0.76 (0.79) for the 2-, 5-, and 10-year composite (mortality) outcomes, respectively. In addition to estimating the survival probability, our method can quantify the uncertainty associated with the prediction. The uncertainty scores show a consistent correlation with the prediction accuracy. We find PSA and prostate cancer stage information are the most important indicators in risk prediction. Our work demonstrates the utility of the data-driven machine learning model in prostate cancer risk prediction, which can play a critical role in the clinical decision system.

Investigating the Role of Dahuang in Hepatoma Treatment Using Network Pharmacology, Molecular Docking, and Survival Analysis.

Hepatoma is one of the most common malignant tumors. The incidence rate is high in developing countries, and China has the most significant number of cases. Dahuang is a classic traditional antitumor drug commonly used in China and has also been applied to treat hepatoma. However, the potential mechanism of Dahuang in treating hepatoma is not clear. Therefore, this study is aimed at elucidating the possible molecular mechanism and key targets of Dahuang using methods of network pharmacology, molecular docking, and survival analysis. Firstly, the active ingredients and key targets of Dahuang were analyzed through public databases, and then the drug-ingredient-target-disease network diagram of Dahuang against hepatoma was constructed. Five main active components and five core targets were determined according to the enrichment degree. Enrichment analysis demonstrated that Dahuang treated hepatoma through the multiple pathways in cancer. Additionally, molecular docking predicted that aloe-emodin and PIK3CG depicted the best binding energy. Survival analysis indicated that a high/ESR1 gene expression had a relatively good prognosis for patients with hepatoma (p < 0.05). In conclusion, the current study results demonstrated that Dahuang could treat hepatoma through a variety of active ingredients, targets, and multiantitumor pathways. Moreover, it effectively improved the prognosis of hepatoma patients. ESR1 is the potential key gene that is beneficial for the survival of hepatoma patients. Also, aloe-emodin and beta-sitosterol are the two main active crucial ingredients for hepatoma treatment. The study also provided some functional bases and references for the development of new drugs, target mining, and experimental animal research of hepatoma in the future.

Utilizing Bioinformatics Technology to Explore the Potential Mechanism of Danggui Buxue Decoction against NSCLC.

While lung cancer poses a serious threat to human health, non-small-cell lung cancer (NSCLC) is the most common type of lung cancer. Danggui Buxue Decoction (DBD) is a classical traditional antitumor medicine commonly used in China. However, the potential mechanism of DBD against NSCLC has not yet been expounded. Therefore, this study clarified the potential molecular mechanism and key targets of DBD in NSCLC treatment through several technological advances, such as network pharmacology, molecular docking, and bioinformatics. Firstly, the relative active ingredients and key DBD targets were analyzed, and subsequently, a drug-ingredient-target-disease network diagram was constructed for NSCLC treatment with DBD, resulting in the identification of five main active ingredients and ten core targets according to the enrichment degree. The enrichment analysis revealed that DBD can achieve the purpose of treating NSCLC through the AGE-RAGE signaling pathway in diabetic complications. Secondly, the molecular docking approach predicted that quercetin and hederagenin have the best working mechanisms with PDE3A and PTGS1, while the survival analysis results depicted that high PDE3A gene expression has a relatively poor prognosis for NSCLC patients (p < 0.05). Additionally, PDE3A is mainly distributed in the LU65 cell line that originated from Asian population. In summary, our study results showed that DBD can treat NSCLC through the synergistic correlation between multiple ingredients, multiple targets, and multiple pathways, thus effectively improving NSCLC prognosis. This study not only reflected the medicinal value of DBD but also provided a solid structural basis for future new drug developments and targeted therapies.

Development of prognostic predictive model with neutrophil-lymphocyte ratio (NLR) in patients with gastric signet ring carcinoma.

ABSTRACT: The risk factors have not been well-defined for prognosis in gastric signet ring cell carcinoma (GSRC) patients. This study is designed to prognosticate survival in GSRC patients by establishing and verifying a predictive model with neutrophil-lymphocyte ratio (NLR).A total of 147 GSRC patients from Department of Surgical Oncology, Neimenggu Baogang Hospital, Inner Mongolia Medical University were retrospectively reviewed. A predictive model was established using Cox proportional hazards. The performance of the model was evaluated by ROC curves.In present study, we found that overall survival (OS) (P < .001, Fig. 1A) and tumor recurrence rate (P = .036, Fig. 1B) in the NLR ≤ 2.8 group were significantly better than those in the NLR > 2.8 group. These results showed that NLR ≤ 2.8 was significant prognostic factor related with both OS and tumor recurrence in patients with GSRC. After adjusting for competing risk factors, NLR ≤ 2.8 (hazard ratio [HR]: 2.625, 95% confidence interval [CI]: 1.505-5.3166, P = .003), tumor size (HR: 3.024, 95% CI: 1.521-4.186, P = .005), and tumor metastasis (HR: 3.303, 95% CI: 1.25-4.525, P = .012) remained independent predictors of tumor recurrence rate and OS. Our results showed that comparing with the model without NLR (area under ROC curve: 0.798), the model with NLR (area under ROC curve: 0.826) had significant better predictive power than the model without NLR, which further confirmed the value of NLR in predicting prognosis of patients with GSRC.In conclusion, a high NLR value independently predicts poor survival in patients with GSRC after surgery. The NLR may help oncologists evaluate outcomes of patients received surgical resection and chemotherapy in order to choose alternative therapies for patients with high NLR value.

Pancreatic Neuroendocrine Tumor: Rationale for Centralization in an Integrated Health Care System.

OBJECTIVES: Given the complex surgical management and infrequency of pancreatic neuroendocrine tumor, we hypothesized that treatment at a center of excellence improves survival. METHODS: Retrospective review identified 354 patients with pancreatic neuroendocrine tumor treated between 2010 and 2018. Four hepatopancreatobiliary centers of excellence were created from 21 hospitals throughout Northern California. Univariate and multivariate analyses were performed. The χ2 test of clinicopathologic factors determined which were predictive for overall survival (OS). RESULTS: Localized disease was seen in 51% of patients, and metastatic disease was seen in 32% of patients with mean OS of 93 and 37 months, respectively (P < 0.001). On multivariate survival analysis, stage, tumor location, and surgical resection were significant for OS (P < 0.001). All stage OS for patients treated at designated centers was 80 and 60 months for noncenters (P < 0.001). Surgery was more common across stages at the centers of excellence versus noncenters at 70% and 40%, respectively (P < 0.001). CONCLUSIONS: Pancreatic neuroendocrine tumors are indolent but have malignant potential at any size with management often requiring complex surgeries. We showed survival was improved for patients treated at a center of excellence, where surgery was more frequently utilized.

Supervised Graph Clustering for Cancer Subtyping Based on Survival Analysis and Integration of Multi-Omic Tumor Data.

Identifying cancer subtypes by integration of multi-omic data is beneficial to improve the understanding of disease progression, and provides more precise treatment for patients. Cancer subtypes identification is usually accomplished by clustering patients with unsupervised learning approaches. Thus, most existing integrative cancer subtyping methods are performed in an entirely unsupervised way. An integrative cancer subtyping approach can be improved to discover clinically more relevant cancer subtypes when considering the clinical survival response variables. In this study, we propose a Survival Supervised Graph Clustering (S2GC)for cancer subtyping by taking into consideration survival information. Specifically, we use a graph to represent similarity of patients, and develop a multi-omic survival analysis embedding with patient-to-patient similarity graph learning for cancer subtype identification. The multi-view (omic)survival analysis model and graph of patients are jointly learned in a unified way. The learned optimal graph can be unitized to cluster cancer subtypes directly. In the proposed model, the survival analysis model and adaptive graph learning could positively reinforce each other. Consequently, the survival time can be considered as supervised information to improve the quality of the similarity graph and explore clinically more relevant subgroups of patients. Experiments on several representative multi-omic cancer datasets demonstrate that the proposed method achieves better results than a number of state-of-the-art methods. The results also suggest that our method is able to identify biologically meaningful subgroups for different cancer types. (Our Matlab source code is available online at github: https://github.com/CLiu272/S2GC).