Early-onset and later-onset cancer: trends, risk factors, and prevention in Northern China.

The characteristics of early-onset (onset age <50 years) and later-onset (onset age ≽ 50 years) cancers differ significantly. Identifying novel risk factors for both types of cancer is crucial for increasing awareness of cancer prevention and for reducing its burden. This study aimed to analyze the trends in incidence and risk factors for early-onset and late-onset cancers. We conducted a prospective study by drawing data from the Kailuan Study. This study included 6,741 participants with cancer (624 with early-onset cancer and 6,117 with later-onset cancer) and 6,780 matched controls among the 186,249 participants who underwent Kailuan health examinations from 2006 to 2019. The primary outcomes were cancer incidence rates, and associated risk factors for early- and later-onset cancer. Weighted Cox regression was used to calculate hazard ratios and 95% confidence intervals of each exposure factor for early- and later-onset cancer by cancer type. Population-attributable risk proportions were used to estimate the number of cases that could be prevented by eliminating a risk factor from the population. Except for liver cancer, incidence rates for nearly all types of cancer increased during the study period. Smoking, alcohol consumption, lipid metabolism disorders, hypertension, diabetes mellitus, fatty liver, and inflammation were associated with a significantly increased risk of cancer at multiple sites, but risk factors for cancer incidence differed by site. Smoking, alcohol consumption, inflammation, and hypertension were the major contributors to preventable cancer. The incidence of several different types of cancer, including early-onset cancer, is increasing in northeastern China. Differences in risk factors between early-onset and later-onset malignancies may contribute to the divergence in the observed changes in incidence trends between these two specific types of cancer.

Causal relationship of interleukin-6 and its receptor on sarcopenia traits using mendelian randomization.

BACKGROUND: Previous research has extensively examined the role of interleukin 6 (IL-6) in sarcopenia. However, the presence of a causal relationship between IL-6, its receptor (IL-6R), and sarcopenia remains unclear. METHOD: In this study, we utilized summary-level data from genome-wide association studies (GWAS) focused on appendicular lean mass (ALM), hand grip strength, and walking pace. Single nucleotide polymorphisms (SNPs) were employed as genetic instruments for IL-6 and IL-6R to estimate the causal effect of sarcopenia traits. We adopted the Mendelian randomization (MR) approach to investigate these associations using the inverse variance weighted (IVW) method as the primary analytical approach. Additionally, we performed sensitivity analyses to validate the reliability of the MR results. RESULT: This study revealed a significant negative association between main IL-6R and eQTL IL-6R on the left grip strength were - 0.013 (SE = 0.004, p < 0.001) and -0.029 (SE = 0.007, p < 0.001), respectively. While for the right grip strength, the estimates were - 0.011 (SE = 0.001, p < 0.001) and - 0.021 (SE = 0.008, p = 0.005). However, no evidence of an association for IL-6R with ALM and walking pace. In addition, IL-6 did not affect sarcopenia traits. CONCLUSION: Our study findings suggest a negative association between IL-6R and hand grip strength. Additionally, targeting IL-6R may hold potential value as a therapeutic approach for the treatment of hand grip-related issues.

Locoregional treatment improves overall survival for liver cancer during second-line regorafenib or immune checkpoint inhibitor.

For advanced hepatocellular carcinoma (HCC), the best second-line treatment after first-line treatment with sorafenib is unclear. This study aimed to compared the efficacy of second-line regorafenib (a tyrosine kinase inhibitor) and immune checkpoint inhibitors (ICIs) in patients with advanced HCC after sorafenib therapy. This retrospective study included 89 patients with HCC treated with sorafenib, and then regorafenib (n = 58) or an ICI (n = 31). Treatment response, overall survival (OS) and progression-free survival (PFS) of the 2 groups were compared, and factors associated with post-treatment mortality or disease progression were evaluated. During follow-up period, compared to regorafenib, treatment with an ICI results in a slight increase in a 20% decrease of AFP (35.7% vs. 31.8%), complete response rate (6.5% vs. 0%), objective response rate (16.1% vs. 6.9%), median overall survival (13.3 vs. 5 months), and median PFS (3.0 vs. 2.6 months). Combined locoregional treatment (LRT) (hazard ratio [HR] = 0.40, 95% confidence interval [CI]: 0.15-0.99) during second-line treatment was associated with a decreased risk of post-treatment mortality. After propensity scoring matching, combined LRT during second-line treatment had longer post-treatment OS than patients without combined LRT. A 20% decrease of AFP (HR = 0.54, 95% CI: 0.31-0.94) was associated with a decreased risk of post-treatment disease progression. In conclusions, second-line treatment with regorafenib or ICI prolongs OS in patients with advanced HCC treated with sorafenib. Combined LRT during second-line treatment is associated with decreased post-treatment mortality. A 20% decrease of AFP level may be predictive of a lower rate of disease progression.

The association of metabolic syndrome score trajectory patterns with risk of all cancer types.

BACKGROUND: Metabolic syndrome (MetS) elevates cancer risk. However, a single MetS assessment does not fully reveal the long-term association with cancer. Inflammation, alongside MetS, could synergistically expedite both the onset and advancement of cancer. This study aims to investigate MetS score trajectories and cancer risk in a large, prospective cohort study. METHODS: The authors prospectively examined the relationship between MetS score trajectory patterns and new-onset cancer in 44,115 participants. Latent mixture modeling was used to identify the MetS score trajectories. Cox proportional hazards regression models were used to evaluate the association between MetS score trajectory patterns and the risk of overall and site-specific cancers. RESULTS: Four MetS score trajectory patterns were identified: low-stable (n = 4657), moderate-low (n = 18,018), moderate-high (n = 18,288), and elevated-increasing (n = 3152). Compared to participants with a low-stable trajectory pattern, the elevated-increasing trajectory pattern was associated with an elevated risk of overall (hazard ratio [HR], 1.27; 95% confidence interval [CI], 1.04-1.55), breast (HR, 2.11; 95% CI, 1.04-4.34), endometrial (HR, 3.33; 95% CI, 1.16-6.77), kidney (HR, 4.52; 95% CI, 1.17-10.48), colorectal (HR, 2.54; 95% CI, 1.27-5.09), and liver (HR, 1.61; 95% CI, 1.09-4.57) cancers. Among participants with chronic inflammation (C-reactive protein levels ≥3 mg/L), the elevated-increasing trajectory pattern was significantly associated with subsequent breast, endometrial, colorectal, and liver cancers. CONCLUSIONS: Trajectories of MetS scores are associated with the occurrence of cancers, especially breast, endometrial, kidney, colorectal, and liver cancers, emphasizing the importance of long-term monitoring and evaluation of MetS. PLAIN LANGUAGE SUMMARY: The association between long-term elevated metabolic syndrome (MetS) scores and a heightened risk of various cancers is a pivotal finding of our study. Our research further indicates that individuals with MetS, particularly when coupled with chronic inflammation, are at an increased risk of cancer. We propose that sustained monitoring and management of MetS could be beneficial in reducing cancer risk.

Concurrent Atezolizumab Plus Bevacizumab and High-Dose External Beam Radiotherapy for Highly Advanced Hepatocellular Carcinoma.

BACKGROUND: Atezolizumab plus bevacizumab (atezo-bev) has been recommended for advanced hepatocellular carcinoma (HCC). High-dose external beam radiotherapy (RT) is recognized for its excellent local tumor control. The efficacy and safety of concurrent atezo-bev with RT for highly advanced HCC has been minimally explored. METHODS: In this preliminary retrospective study, we assessed patients with highly advanced HCC, characterized by Vp4 portal vein thrombosis or tumors exceeding 50% of liver volume, who received concurrent atezo-bev and RT (group A). Group A included 13 patients who received proton radiation at a dose of 72.6 GyE in 22 fractions, and one patient who received photon radiation at a dose of 54 Gy in 18 fractions. This group was compared with 34 similar patients treated atezo-bev alone as a control (group B). The primary objectives were to evaluate the objective response rate (ORR), overall survival (OS), and safety. RESULTS: Baseline characteristics were similar between groups, except for a higher incidence of Vp4 portal vein thrombosis in group A (78.6% vs. 21.4%, P = .05). Group A achieved a higher ORR (50.0% vs. 11.8%, P < .01) and a longer OS (not reached vs. 5.5 months, P = .01) after a median follow-up of 5.2 months. Multivariate analysis indicated that concurrent RT independently favored longer OS (hazard ratio: 0.18; 95% CI, 0.05-0.63, P < .01). Group A did not increase any grade adverse events (78.6% vs. 58.8%, P = .19) or severe adverse events of grade ≥ 3 (14.3% vs. 14.7%, P = .97) compared to group B. CONCLUSIONS: The concurrent high-dose external beam radiotherapy appears to safely enhance the effectiveness of atezolizumab plus bevacizumab for highly advanced patients with HCC. Further studies are warranted to confirm these findings.

Endoscopic ultrasonography-related diagnostic accuracy and clinical significance on small rectal neuroendocrine neoplasms.

This research aimed to examine the diagnostic accuracy and clinical significance of endoscopic ultrasonography (EUS) in the context of small rectal neuroendocrine neoplasms (NENs). A total of 108 patients with rectal subepithelial lesions (SELs) with a diameter of < 20 mm were included in the analysis. The diagnosis and depth assessment of EUS was compared to the histology findings. The prevalence of NENs in rectal SELs was 78.7% (85/108). The sensitivity of EUS in detecting rectal NENs was 98.9% (84/85), while the specificity was 52.2% (12/23). Overall, the diagnostic accuracy of EUS in identifying rectal NENs was 88.9% (96/108). The overall accuracy rate for EUS in assessing the depth of invasion in rectal NENs was 92.9% (78/84). Therefore, EUS demonstrates reasonable diagnostic accuracy in detecting small rectal NENs, with good sensitivity but inferior specificity. EUS may also assist physicians in assessing the depth of invasion in small rectal NENs before endoscopic excision.

Subsequent locoregional therapy prolongs survival in progressive hepatocellular carcinoma patients under lenvatinib treatment.

BACKGROUND: Locoregional therapy and multi-kinase inhibitor agent have been the backbone of treatment for hepatocellular carcinoma (HCC) patients. However, the effect of combination or sequential use of locoregional therapy on HCC patients receiving multi-kinase inhibitor remain uncertain. Therefore, we aim to explore whether the subsequent locoregional therapy provides better survival in HCC patients under lenvatinib treatment. METHODS: From March 2018 to April 2020, a total of 78 unresectable HCC patients receiving lenvatinib were recruited. Image response was evaluated by dynamic image using the modified RECIST criteria. Among patients with tumor progression under lenvatinib treatment, whether receiving subsequent locoregional therapy or not were documented. Overall survival between two groups and the predictors for tumor progression were also analyzed. RESULTS: Among the 78 patients receiving lenvatinib, the median age was 67.8 years old, and 69.2 % were male. Forty-four patients (56.4 %) experienced tumor progression with time to progression 5.1 months (95 % confidence interval (CI): 4.7-6.8) months. In multivariable Cox regression analysis, albumin-bilirubin (ALBI) grade II (adjusted HR: 2.883, P = 0.0104), and treatment duration less than three months (adjusted HR: 3.801, P = 0.0014) were the independent predictive factors for tumor progression, while patients achieving objective response under lenvatinib treatment within 12 weeks was the independent protective factor for tumor progression (adjusted HR: 0.144, P = 0.0020). Among the 44 patients with tumor progression, twenty-six (59.1 %) patients received subsequent locoregional therapy after tumor progression. Comparing to those with tumor progression without locoregional treatment, patients who received subsequent locoregional therapy had significantly better survival (1st year cumulative survival rate 70 % vs 27 %, log-rank P = 0.003). CONCLUSION: ALBI grade, treatment duration of lenvatinib, and achieving objective image response within twelve weeks were the independent predictive factors for tumor progression. Furthermore, longer overall survival was observed in tumor progression patients with subsequent locoregional therapy and with better liver preserved function.

Geriatric Nutritional Risk Index Combined with Calf Circumference Can be a Good Predictor of Prognosis in Patients Undergoing Surgery for Gastric or Colorectal Cancer.

OBJECTIVES: To explore the effect of combined hematological and physical measurement indicators on the prognosis of patients undergoing surgery for gastric or colorectal cancer and to screen for the best prognostic indicators. INTRODUCTION: Gastric and colorectal cancer is a widespread health concern worldwide and one of the major contributors to cancer-related death. The hematological and physical measurement indicators have been shown to associate with the prognosis of patients undergoing surgery for gastric or colorectal cancer, respectively, but it is still unclear whether the combination of the two can reflect the prognosis more effectively. METHODS: Thirteen hematological indicators and 5 physical measurement indicators were selected in this study, and the most promising ones were screened using LASSO regression. Then, the best prognostic indicators were selected by time-ROC curves. Survival curves were constructed using the Kaplan-Meier method, and the effects of hematological and physical measurement indicators on the prognosis of patients undergoing surgery for gastric or colorectal cancers were evaluated by Cox proportional risk regression analysis. In addition, the relationship between hematological and physical measurement indicators on secondary outcomes, including length of stay, hospitalization costs, intensive care unit (ICU) admission, and patients' subjective global assessment scores (PGSGA), was explored. RESULTS: After initial screening, among the hematological indicators, the geriatric nutritional risk index (GNRI) showed the highest mean area under the curve (AUC) values. Among body measures, calf circumference (CC) showed the highest mean AUC value. Further analyses showed that the combination of combined nutritional prognostic index (GNRI) and calf circumference (CC) (GNRI-CC) had the best performance in predicting the prognosis of patients undergoing surgery for gastric or colorectal cancers. Low GNRI, low CC, and low GNRI-low CC increased the risk of death by 44%, 48%, and 104%, respectively. Sensitivity analyses showed the same trend. In addition, low GNRI-low CC increased the risk of malnutrition by 17%. CONCLUSION: This study emphasizes that a combination of blood measures and body measures is essential to accurately assess the prognosis of patients undergoing surgery for gastric or colorectal cancers. The GNRI-CC is a good prognostic indicator and can also assess the risk of possible malnutrition.

Molecular features of the ligand-free GLP-1R, GCGR and GIPR in complex with Gs proteins.

Class B1 G protein-coupled receptors (GPCRs) are important regulators of many physiological functions such as glucose homeostasis, which is mainly mediated by three peptide hormones, i.e., glucagon-like peptide-1 (GLP-1), glucagon (GCG), and glucose-dependent insulinotropic polypeptide (GIP). They trigger a cascade of signaling events leading to the formation of an active agonist-receptor-G protein complex. However, intracellular signal transducers can also activate the receptor independent of extracellular stimuli, suggesting an intrinsic role of G proteins in this process. Here, we report cryo-electron microscopy structures of the human GLP-1 receptor (GLP-1R), GCG receptor (GCGR), and GIP receptor (GIPR) in complex with Gs proteins without the presence of cognate ligands. These ligand-free complexes share a similar intracellular architecture to those bound by endogenous peptides, in which, the Gs protein alone directly opens the intracellular binding cavity and rewires the extracellular orthosteric pocket to stabilize the receptor in a state unseen before. While the peptide-binding site is partially occupied by the inward folded transmembrane helix 6 (TM6)-extracellular loop 3 (ECL3) juncture of GIPR or a segment of GCGR ECL2, the extracellular portion of GLP-1R adopts a conformation close to the active state. Our findings offer valuable insights into the distinct activation mechanisms of these three important receptors. It is possible that in the absence of a ligand, the intracellular half of transmembrane domain is mobilized with the help of Gs protein, which in turn rearranges the extracellular half to form a transitional conformation, facilitating the entry of the peptide N-terminus.

Tricuspid mechanical valve replacement for severe tricuspid stenosis in a child who underwent surgical correction of complete atrioventricular septal defect, a rare long-term complications.

BACKGROUND: Complete atrioventricular septal defect is a complicated congenital heart malformations, and surgical correction is the best treatment, the severe tricuspid stenosis is a rare long-term complication after the surgery. CASE PRESENTATION: We report a case with the complication of severe tricuspid stenosis 7 years after the surgical correction of complete atrioventricular septal defect in a child. Then the patient underwent tricuspid mechanical valve replacement, Glenn, atrial septostomy, and circumconstriction of the right pulmonary artery. CONCLUSIONS: The patient recovered successfully with good short-term.

Investigating the relationship between muscle mass and nasal Methicillin-Resistant Staphylococcus aureus (MRSA) colonization: Analysis of the National Health and Nutrition Examination Survey (NHANES).

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) nasal colonization is associated with an increased risk of infection disease. Low muscle mass has been linked to higher levels of inflammatory markers and weakened immune response, which may impact the susceptibility to nasal MRSA colonization. The relationship between muscle function and immune response to pathogens may be bidirectional. This study investigates the association between muscle mass and nasal MRSA colonization in adults. METHODS: The present cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES) conducted between 2001 and 2004. Appendicular skeletal muscle mass (ASM) adjusted by body mass index (BMI) (ASM/BMI) was used to evaluate muscle mass. Multivariate logistic regression, adjusted for demographic and infection factors, was used to analyze the association between muscle mass and nasal colonization by MRSA. A subgroup analysis based on age and gender was performed to assess the impact of muscle mass on nasal MRSA colonization. RESULTS: Nasal MRSA colonization was more prevalent in females, those with smaller household sizes, lower income, lower ASM/BMI, those who had stayed in healthcare facilities in the past 12 months, and individuals with diabetes and smoking habits. After adjusting for confounding factors, a dose-dependent association was found between decreasing quartiles of ASM/BMI and the risk of nasal MRSA colonization (p < 0.05). Additionally, per 1 unit increase in ASM/BMI was related to a 64% lower risk of nasal MRSA colonization. CONCLUSIONS: This study suggests a significant negative correlation between ASM/BMI and the risk of nasal MRSA colonization. However, more prospective studies are required to investigate the causal relationship between muscle mass and colonization.

Systemic inflammation and insulin resistance-related indicator predicts poor outcome in patients with cancer cachexia.

BACKGROUND: The C-reactive protein (CRP)-triglyceride-glucose (TyG) index (CTI), which is a measure representing the level of inflammation and insulin resistance (IR), is related to poor cancer prognosis; however, the CTI has not been validated in patients with cancer cachexia. Thus, this study aimed to explore the potential clinical value of the CTI in patients with cancer cachexia. METHODS: In this study, our prospective multicenter cohort included 1411 patients with cancer cachexia (mean age 59.45 ± 11.38, 63.3% male), which was a combined analysis of multiple cancer types. We randomly selected 30% of the patients for the internal test cohort (mean age 58.90 ± 11.22% 61.4% male). Additionally, we included 307 patients with cancer cachexia in the external validation cohort (mean age 61.16 ± 11, 58.5% male). Receiver operating characteristic (ROC) and calibration curves were performed to investigate the prognostic value of CTI. The prognostic value of the CTI was also investigated performing univariate and multivariate survival analyses. RESULTS: The survival curve indicated that the CTI showed a significant prognostic value in the total, internal, and external validation cohorts. Prognostic ROC curves and calibration curves revealed that the CTI showed good consistency in predicting the survival of patients with cancer cachexia. Multivariate survival analysis showed that an elevated CTI increased the risk of death by 22% (total cohort, 95% confidence interval [CI] = 1.13-1.33), 34% (internal test cohort, 95%CI = 1.11-1.62), and 35% (external validation cohort, 95%CI = 1.14-1.59) for each increase in the standard deviation of CTI. High CTI reliably predicted shorter survival (total cohort, hazard ratio [HR] = 1.45, 95%CI = 1.22-1.71; internal test cohort, HR = 1.62, 95%CI = 1.12-2.36; external validation cohort, HR = 1.61, 95%CI = 1.15-2.26). High CTI significantly predicted shorter survival in different tumor subgroups, such as esophageal [HR = 2.11, 95%CI = 1.05-4.21] and colorectal cancer [HR = 2.29, 95%CI = 1.42-3.71]. The mediating effects analysis found that the mediating proportions of PGSGA, ECOG PS, and EORTC QLQ-C30 on the direct effects of CTI were 21.72%, 19.63%, and 11.61%, respectively We found that there was a significant positive correlation between the CTI and 90-day [HR = 2.48, 95%CI = 1.52-4.14] and 180-day mortality [HR = 1.77,95%CI = 1.24-2.55] in patients with cancer cachexia. CONCLUSION: The CTI can predict the short- and long-term survival of patients with cancer cachexia and provide a useful prognostic tool for clinical practice.

Reexamining the effects of drug loading on the in vivo performance of PEGylated liposomal doxorubicin.

Higher drug loading employed in nanoscale delivery platforms is a goal that researchers have long sought after. But such viewpoint remains controversial because the impacts that nanocarriers bring about on bodies have been seriously overlooked. In the present study we investigated the effects of drug loading on the in vivo performance of PEGylated liposomal doxorubicin (PLD). We prepared PLDs with two different drug loading rates: high drug loading rate, H-Dox, 12.9% w/w Dox/HSPC; low drug loading rate, L-Dox, 2.4% w/w Dox/HSPC (L-Dox had about 5 folds drug carriers of H-Dox at the same Dox dose). The pharmaceutical properties and biological effects of H-Dox and L-Dox were compared in mice, rats or 4T1 subcutaneous tumor-bearing mice. We showed that the lowering of doxorubicin loading did not cause substantial shifts to the pharmaceutical properties of PLDs such as in vitro and in vivo stability (stable), anti-tumor effect (equivalent effective), as well as tissue and cellular distribution. Moreover, it was even more beneficial for mitigating the undesired biological effects caused by PLDs, through prolonging blood circulation and alleviating cutaneous accumulation in the presence of pre-existing anti-PEG Abs due to less opsonins (e.g. IgM and C3) deposition on per particle. Our results warn that the effects of drug loading would be much more convoluted than expected due to the complex intermediation between nanocarriers and bodies, urging independent investigation for each individual delivery platform to facilitate clinical translation and application.

The age-related obesity paradigm: results from two large prospective cohort studies.

BACKGROUND: The obesity paradigm has been a health concern globally for many years, its meaning is controversial. In this study, we assess the characteristics and causes of obesity paradigm and detail the mediation of obesity and inflammation on survival. METHODS: The original cohort included participants from the US National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018, a prospective cohort of a nationally representative sample of adult participants; the oncology validation cohort included patients from the Investigation on Nutrition Status and Clinical Outcome of Common Cancers (INSCOC) from 2013 to 2021, a prospective cohort of Chinese patients with cancer. Survival analysis was performed using weighted (NHANES) or unweighted (INSCOC) Cox survival analyses. The normal BMI group was used as a reference for all comparisons. Systemic inflammation was defined as neutrophil-to-lymphocyte ratio (NLR) > 3. Model-based causal mediation analysis was used to identify the mediators. RESULTS: A total of 52 270 (weighted population: 528506229) participants of the NHANES [mean follow-up times: 10.2 years; mean age (SD): 47 (19.16) years] were included in the original cohort; and a total of 17 418 patients with cancer of INSCOC [mean follow-up times: 2.9 years; mean age (SD): 57.37 (11.66) years] were included in the validation cohort. In the subgroups of all the participants, the obesity paradigm was more apparent in older participants and participants with disease [HR (95% CI): age ≥ 65 years, 0.84 (0.76, 0.93); with cancer, 0.84 (0.71, 0.99); with CVD, 0.74 (0.65, 0.85)]. As aged, the protective effect of a high BMI on survival gradually increased and a high BMI showed the effect of a protective factor on older participants [for obese II, HR (95% CI): young adults, 1.91 (1.40, 2.62); middle age, 1.56 (1.28, 1.91); old adults, 0.85 (0.76, 0.96]). The aged-related obesity paradigm in patients with cancer from the NHANES was verified in the INSCOC cohorts [for obese, HR (95%CI): 0.65 (0.52, 0.81)]. The NLR is an important mediator of the effect of BMI on survival (proportion of mediation = 15.4%). CONCLUSIONS: The obesity paradigm has a strong correlation with age. Relative to normal weight, obese in young people was association with higher all-cause mortality, and obese in elderly people was not association with higher mortality. The protection of obesity is association with systemic inflammation.

Delta Radiomics Based on Longitudinal Dual-modal Ultrasound Can Early Predict Response to Neoadjuvant Chemotherapy in Breast Cancer Patients.

RATIONALE AND OBJECTIVES: To develop a monitoring model using radiomics analysis based on longitudinal B-mode ultrasound (BUS) and shear wave elastography (SWE) to early predict pathological response to neoadjuvant chemotherapy (NAC) in breast cancer patients. MATERIALS AND METHODS: In this prospective study, 112 breast cancer patients who received NAC between September 2016 and March 2022 were included. The BUS and SWE data of breast cancer were obtained prior to treatment as well as after two and four cycles of NAC. Radiomics features were extracted followed by measuring the changes in radiomics features compared to baseline after the second and fourth cycles of NAC (△R [C2], △R [C4]), respectively. The delta radiomics signatures were established using a support vector machine classifier. RESULTS: The area under receiver operating characteristic curve (AUC) values of △RBUS (C2) and △RBUS (C4) for predicting the response to NAC were 0.83 and 0.84, while those of △RSWE (C2) and △RSWE (C4) were 0.88 and 0.90, respectively. △RSWE exhibited significantly superior performance to △RBUS for predicting NAC response (Delong test, p < 0.01). No significant differences were observed in the performances between △R (C2) and △R (C4) based on BUS or SWE data. The longitudinal dual-modal ultrasound radiomics (LDUR) model had an excellent discrimination, good calibration and clinical usefulness, with the AUC, sensitivity and specificity of 0.97, 95.52% and 91.11%, respectively. CONCLUSION: The LDUR model achieved excellent performance in predicting the pathological response to chemotherapy during the early stages of NAC for breast cancer.

A combination of locoregional treatment with systemic therapy after atezolizumab plus bevacizumab failure for unresectable hepatocellular carcinoma provides survival benefit.

Atezolizumab plus bevacizumab (A+B) is used to treat unresectable hepatocellular carcinoma (HCC), but the optimal rescue therapy after A+B remains unclear. Combining locoregional therapy (LRT) with systemic treatment has been shown to improve tumor control, but the role in patients who fail A+B is unknown. We retrospectively enrolled patients who experienced radiological progression after A+B. Objective response rate (ORR), disease control rate (DCR), post progression survival (PPS), and secondary progression-free survival (PFS) were evaluated by modified RECIST. Inverse probability weighting (IPW) was used to balance baseline clinical features. A total of 61 patients were enrolled with a median age of 60.7 years, 83.6% male, 88.5% viral hepatitis-related, and 60.7% without prior systemic treatment before A+B. Patients receiving sequential therapies had significantly longer PPS than supportive care (10.5 vs. 2.3 months, P<0.0001). Among 37 patients received sequential systemic treatment, 18 received combined LRT. The median follow-up after post A+B failure was 6.6 months. The combined LRT group had higher ORR (27.8 vs. 0%, P=0.0197) and DCR (72.2 vs. 26.3%, P=0.0052) than systemic alone group. The median PPS and secondary PFS were significantly longer in combined LRT group (PPS: 12.2 vs. 5.8 months, P=0.0070; PFS: 5.0 vs. 2.6 months, P=0.0134) than systemic alone group. After IPW analysis, patients with combined LRT had superior PPS and secondary PFS. The incidence rates of AEs were higher in LRT combination compared to systemic alone (any grade AEs: 94.4 vs. 63.2%, P=0.0422; severe AEs: 33.3 vs. 5.3%, P=0.0422). No significant albumin-bilirubin index changed in the first 3 months in combined LRT group (0.966 [0.647-1.443], P=0.867) though a trend of deterioration in systemic alone group. In conclusion, sequential systemic therapy provides survival benefits after A+B failure. Furthermore, combining LRT with systemic treatment could provide better tumor responses and survival benefits with acceptable toxicity than systemic therapy alone.

Association of the age of onset of metabolic syndrome with the risk of all cancer types.

BACKGROUND: The association between the age at onset of metabolic syndrome and cancer risk remains unknown. This study explored the association between age at metabolic syndrome onset and the risk of overall and site-specific cancer incidence. METHODS: This study included 31,688 participants with new-onset metabolic syndrome and 31,688 participants matched according to sex, age (±1 y), and examination year among the 179,328 participants who underwent Kailuan health examinations from 2006 to 2017 in Tangshan, China. Weighted Cox regression was used to calculate the hazard ratios and 95% confidence intervals of new-onset metabolic syndrome for overall and site-specific cancer incidence across age groups. Population-attributable risk proportions were used to estimate the number of cases that could be prevented by eliminating the risk factors from the population. RESULTS: During an average follow-up period of 10.22 y, we identified 2,710 cases of cancer and 4,218 deaths that occurred before the diagnosis of cancer. With an increase in metabolic syndrome onset age, the hazards of overall cancer incidence were gradually attenuated. The average hazard ratios (95% confidence intervals) of overall cancer were 1.94 (1.25-2.99) for metabolic syndrome onset age <45 year old, 1.41 (1.15-1.71) for age 45-54 years old, 1.38 (1.11-1.73) for age 55-64 years old, and 1.07 (0.89-1.28) for age ≥65 years old, respectively (p for interaction = 0.005). Similar results were obtained for colorectal, liver, and breast cancers in the site-specific analysis. CONCLUSIONS: New-onset metabolic syndrome was associated with a higher risk of overall cancer and incidence of several types of cancer, and the associations were stronger with a younger age of onset. TRIAL REGISTRATION: Kailuan Study, ChiCTR2000029767 (Registered February 12, 2020, https://www.chictr.org.cn/showprojEN.html?proj=48316).

The Extended Surgical Concepts for Hepatocellular Carcinoma in the Era of Immune Checkpoint Inhibitors.

Surgical resection remains one of the most effective curative therapies for HCC. However, the majority of patients have advanced unresectable diseases upon presentation. It is of paramount importance to raise the resectability of patients with HCC. The remarkable objective response rate reported by Phase III IMbrave150 trial has led to the concept of "Atezo/Bev followed by curative conversion (ABC conversion)" for initially unresectable HCC. With this revolutionary treatment strategy, the concept of surgical resection for HCC should be amended. The current opinion illustrated three extended surgical concepts, which could be integrated into clinical practice in the era of immune checkpoint inhibitors (ICI).

Prognostic value of systemic inflammation and for patients with colorectal cancer cachexia.

BACKGROUND: The development and progression of cancer cachexia are connected to systemic inflammation and physical performance. However, few relevant studies have reported the survival outcomes prediction of systemic inflammation and physical performance in patients with colorectal cancer (CRC) cachexia. This study investigated the prognostic prediction value of systemic inflammation and performance status in patients with CRC cachexia. METHODS: This multicentre cohort study prospectively collected 905 patients with CRC (58.3% males, 59.3 ± 11.5 years old). Cancer cachexia was diagnosed according to the 2011 Fearon Cachexia Diagnostic Consensus. The prognostic value of systematic inflammatory indicators was determined using the area under the curve, concordance index, and multivariate survival analysis. Performance status was evaluated with Eastern Coopertive Oncology Group performance score (ECOG-PS). Survival data were analysed using univariate and multivariate Cox regression analyses. RESULTS: The area under the curve, concordance index and survival analysis showed that C-reactive protein (CRP), lymphocyte to CRP ratio (LCR) and CRP to albumin ratio (CAR) were more stable and consistent with the survival of patients with CRC, both in non-cachexia and cachexia populations. Among patients with CRC cachexia, high inflammation [low LCR, hazard ratio (HR) 95% confidence interval (95% CI) = 3.33 (2.08-5.32); high CAR, HR (95% CI) = 2.92 (1.88-4.55); high CRP, HR (95% CI) = 3.12 (2.08-4.67)] indicated a worse prognosis, compared with non-cachexia patients [low LCR, HR (95% CI) = 2.28 (1.65-3.16); high CAR, HR (95% CI) = 2.36 (1.71-3.25); high CRP, HR (95% CI) = 2.58 (1.85-3.60)]. Similarly, among patients with CRC cachexia, high PS [ECOG-PS 2, HR (95% CI) = 1.61 (1.04-2.50); ECOG-PS 3/4, HR (95% CI) = 2.91 (1.69-5.00]) indicated a worse prognosis, compared with patients with CRC without cachexia [ECOG-PS 2, HR (95% CI) = 1.28 (0.90-1.81); ECOG-PS 3/4, HR (95% CI) = 2.41 (1.32-4.39]). Patients with CRC cachexia with an ECOG-PS score of 2 or 3-4 and a high inflammation had a shorter median survival time, compared with patients with an ECOG-PS score of 0/1 and a low inflammation. CONCLUSIONS: The systemic inflammatory markers LCR, CAR and CRP have stable prognostic values in patients with CRC. The ECOG-PS may be an independent risk factor for CRC. Combined evaluation of systemic inflammation and ECOG-PS in patients with CRC cachexia could provide a simple survival prediction.