Lung immune prognostic index is associated with clinical outcomes in recurrent or metastatic (R/M) nasopharyngeal carcinoma receiving immunotherapy: Results from the multicenter, single-arm, phase 2 study.

BACKGROUND: Immune-related biomarkers are linked to the outcomes of cancer immunotherapy. This study evaluates the baseline and longitudinal association between the lung immune prognostic index (LIPI) and immune checkpoint inhibitor outcomes in previously treated recurrent or metastatic (R/M) nasopharyngeal carcinoma (NPC) patients. METHODS: Data from 153 R/M NPC patients (median age = 49.00 years old) enrolled in a multicenter, single-arm, phase 2 study (NCT03848286) were analyzed. Pretreatment LIPI was classified into good and intermediate/poor (inter/poor) groups. Longitudinal LIPI variations were categorized into "Stable good", "Trend to increase", "Trend to decrease", and "Stable inter/poor". Primary and secondary outcomes were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). RESULTS: Pretreatment LIPI was significantly associated with OS (inter/poor vs. good: HR = 2.54, 95 % CI: 1.60-4.04, P < 0.001), PFS [inter/poor vs. good: hazard ratio (HR) = 2.18, 95 % CI: 1.47-3.23, P < 0.001], and DCR [inter/poor vs. good: odd ratio (OR) = 0.26, 95 % CI: 0.12-0.58, P < 0.001)]. Patients with persistently inter/poor LIPI status showed worse OS (HR = 3.25, 95 % CI: 1.84-5.74, P < 0.001), PFS (HR = 2.96, 95 % CI: 1.85-4.74, P < 0.001), and ORR (OR = 0.21, 95 % CI: 0.08-0.56, P < 0.001) compared to the persistently good subgroup. CONCLUSION: Pretreatment LIPI and its longitudinal variations may serve as potential biomarkers for predicting immune checkpoint inhibitor outcomes in R/M NPC patients.

Prognostic effect of triglyceride glucose-related parameters on all-cause and cardiovascular mortality in the United States adults with metabolic dysfunction-associated steatotic liver disease.

BACKGROUNDS: Insulin resistance (IR) plays a vital role in the pathogenesis of the metabolic dysfunction-associated steatotic liver disease (MASLD). However, it remains unclear whether triglyceride-glucose (TyG) related parameters, which serve as useful biomarkers to assess IR, have prognostic effects on mortality outcomes of MASLD. METHODS: Participants in the National Health and Nutrition Examination Survey (NHANES) database from 1999 to 2018 years were included. TyG and its related parameters [TyG-waist circumference (TyG-WC) and TyG-waist to height ratio (TyG-WHtR)] were calculated. Kaplan-Meier curves, Cox regression analysis, and restricted cubic splines (RCS) were conducted to evaluate the association between TyG-related indices with the all-cause and cardiovascular mortality of adults with MASLD. The concordance index (C-index) was used to evaluate the prediction accuracy of TyG-related indices. RESULTS: A total of 8208 adults (4209 men and 3999 women, median age 49.00 years) with MASLD were included in this study. Multivariate-adjusted Cox regression analysis revealed that high quartile levels of TyG-related indices were significantly associated with the all-cause mortality of participants with MASLD [TyGadjusted hazard ratio (aHR) = 1.25, 95% confidence interval (CI) 1.05-1.50, P = 0.014; TyG-WCaHR for all-cause mortality = 1.28, 95% CI 1.07-1.52, P = 0.006; TyG-WHtRaHR for all-cause mortality = 1.50, 95% CI 1.25-1.80, P < 0.001; TyG-WCaHR for cardiovascular mortality = 1.81, 95% CI 1.28-2.55, P = 0.001; TyG-WHtRaHR for cardiovascular mortality = 2.22, 95% CI 1.55-3.17, P < 0.001]. The C-index of TyG-related indices for predicting all-cause mortality was 0.563 for the TyG index, 0.579 for the TyG-WC index, and 0.585 for the TyG-WHtR index, respectively. Regarding cardiovascular mortality, the C-index was 0.561 for the TyG index, 0.607 for the TyG-WC index, and 0.615 for the TyG-WHtR index, respectively. Nonlinear trends were observed between TyG and TyG-WC indices with all-cause mortality of MASLD (P < 0.001 and = 0.012, respectively). A non-linear relationship was observed between the TyG index and cardiovascular mortality of MASLD (P = 0.025). Subgroup analysis suggested that adults aged < 65 years old and those without comorbidities were more sensitive to the mortality prediction of TyG-related indices. CONCLUSION: Findings of this study highlight the predictive value of TyG-related indices, especially the TyG-WHtR index, in the mortality outcomes of adults with MASLD. TyG-related indices would be surrogate biomarkers for the clinical management of MASLD.

Association between BMI trajectories in late-middle age and subsequent dementia risk in older age: a 26-year population-based cohort study.

BACKGROUND: The association between body mass index (BMI) and dementia risk differs depending on follow-up time and age at BMI measurement. The relationship between BMI trajectories in late-middle age (50-65 years old) and the risk of dementia in older age (> 65 years old) has not been revealed. METHODS: In the present study, participants from the Health and Retirement Study were included. BMI trajectories were constructed by combining BMI trend and variation information. The association between BMI trajectories at the age of 50-65 years and dementia risk after the age of 65 years was investigated. Participants with European ancestry and information on polygenic scores for cognitive performance were pooled to examine whether genetic predisposition could modify the association. RESULTS: A total of 10,847 participants were included in the main analyses. A declining BMI trend and high variation in late-middle age were associated with the highest subsequent dementia risk in older age compared with an ascending BMI trend and low variation (RR = 1.76, 95% CI = 1.45-2.13). Specifically, in stratified analyses on BMI trajectories and dementia risk based on each individual's mean BMI, the strongest association between a declining BMI trend with high variation and elevated dementia risk was observed in normal BMI group (RR = 2.66, 95% CI = 1.72-4.1). Similar associations were found when participants were stratified by their genetic performance for cognition function without interaction. CONCLUSIONS: A declining BMI trend and high variation in late-middle age were associated with a higher risk of dementia. Early monitoring of these individuals is needed to prevent dementia in older individuals.

Glycolysis-cholesterol metabolic axis in immuno-oncology microenvironment: emerging role in immune cells and immunosuppressive signaling.

Cell proliferation and function require nutrients, energy, and biosynthesis activity to duplicate repertoires for each daughter. It is therefore not surprising that tumor microenvironment (TME) metabolic reprogramming primarily orchestrates the interaction between tumor and immune cells. Tumor metabolic reprogramming affords bioenergetic, signaling intermediates, and biosynthesis requirements for both malignant and immune cells. Different immune cell subsets are recruited into the TME, and these manifestations have distinct effects on tumor progression and therapeutic outcomes, especially the mutual contribution of glycolysis and cholesterol metabolism. In particularly, glycolysis-cholesterol metabolic axis interconnection plays a critical role in the TME modulation, and their changes in tumor metabolism appear to be a double-edged sword in regulating various immune cell responses and immunotherapy efficacy. Hence, we discussed the signature manifestation of the glycolysis-cholesterol metabolic axis and its pivotal role in tumor immune regulation. We also highlight how hypothetical combinations of immunotherapy and glycolysis/cholesterol-related metabolic interventions unleash the potential of anti-tumor immunotherapies, as well as developing more effective personalized treatment strategies.

Association between inflammatory bowel disease and pancreatic cancer: results from the two-sample Mendelian randomization study.

Background: The nuanced relationship between inflammatory bowel disease (IBD) and pancreatic cancer is noticed in recent years. However, the underlying causal effects of these two diseases are still unclear. Methods: The two-sample mendelian randomization (MR) was conducted to explore the causal effect of IBD condition on pancreatic cancer. Methods of Wald ratio, inverse variance weighted (IVW), MR-Egger, weighted median, and weighted mode were used to investigate the causal relationship between IBD and pancreatic cancer. Besides, Cochrane's Q test, MR-Egger, and leave-one-out method were further conducted to detect heterogeneity, stability, and pleiotropy of MR results. Results: In the MR analysis, we found Crohn's disease had a significant causal effect on pancreatic cancer. Specifically, Crohn's disease would increase 11.1% the risk of pancreatic cancer by the IVW method (p= 0.022), 33.8% by MR Egger (p= 0.015), by 35.3% by the Weighted model (p= 0.005). Regarding ulcerative colitis, there was no statistically significant causal effect observed on pancreatic cancer (p>0.05). Additionally, the pleiotropic test and Leave-one-out analysis both proved the validity and reliability of the present two-sample MR analyses. Conclusion: This study indicates that IBD, particularly Crohn's disease, is causality associated with increased risk of pancreatic cancer. Our results may help public health managers to make better follow-up surveillance of IBD patients.

Frailty trajectory predicts subsequent cognitive decline: A 26-year population-based longitudinal cohort study.

Frailty refers to a decline in the physiological functioning of one or more organ systems. It remained unclear whether variations in the trajectory of frailty over time were associated with subsequent cognitive change. The aim of the current study was to investigate the association between frailty trajectories and subsequent cognitive decline based on the Health and Retirement Study (HRS). A total of 15,454 participants were included. The frailty trajectory was assessed using the Paulson-Lichtenberg Frailty Index, while the cognitive function was evaluated using the Langa-Weir Classification. Results showed that severe frailty was significantly associated with the subsequent decline in cognitive function (ß [95% CI] = -0.21 [-0.40, -0.03], p = 0.03). In the five identified frailty trajectories, participants with mild frailty (inverted U-shaped, ß [95% CI] = -0.22 [-0.43, -0.02], p = 0.04), mild frailty (U-shaped, ß [95% CI] = -0.22 [-0.39, -0.06], p = 0.01), and frailty (ß [95% CI] = -0.34 [-0.62, -0.07], p = 0.01) were all significantly associated with the subsequent cognition decline in the elderly. The current study suggested that monitoring and addressing frailty trajectories in older adults may be a critical approach in preventing or mitigating cognitive decline, which had significant implications for healthcare.

Assessing the role of lipid-lowering therapy on multi-cancer prevention: A mendelian randomization study.

Background: Statin use for cancer prevention has raised wide attention but the conclusions are still controversial. Whether statins use have exact causal effects on cancer prevention remains unclear. Methods: Based on the Genome-Wide Association Studies (GWAS) datasets from the large prospective UK Biobank and other consortium databases, two-sample mendelian randomization (MR) analysis was conducted to explore the causal effects of statins use on varied site-specific cancer risks. Five MR methods were applied to investigate the causality. The stability, heterogeneity, and pleiotropy of MR results were also evaluated. Results: The atorvastatin use could increase the risk of colorectal cancer (odd ratio (OR) = 1.041, p = 0.035 by fixed-effects inverse variance weighted (IVW) method (IVWFE), OR = 1.086, p = 0.005 by weighted median; OR = 1.101, p = 0.048 by weighted mode, respectively). According to the weighted median and weighted mode, atorvastatin could modestly decrease the risk of liver cell cancer (OR = 0.989, p = 0.049, and OR = 0.984, p = 0.004, respectively) and head and neck cancer (OR = 0.972, p = 0.020). Besides, rosuvastatin use could reduce the bile duct cancer risk by 5.2% via IVWEF method (OR = 0.948, p = 0.031). No significant causality was determined in simvastatin use and pan-cancers via the IVWFE or multiplicative random-effects IVW (IVWMRE) method if applicable (p > 0.05). There was no horizontal pleiotropy observed in the MR analysis and the leave-one-out analysis proved the stability of the results. Conclusion: The causalities between statin use and cancer risk were only observed in colorectal cancer and bile duct cancer in the European ancestry population. Future works are warranted to provide more robust evidence for supporting statin repurposing for cancer prevention.

Automated treatment planning for liver cancer stereotactic body radiotherapy.

PURPOSE: To evaluate the quality of fully automated stereotactic body radiation therapy (SBRT) planning based on volumetric modulated arc therapy, which can reduce the reliance on historical plans and the experience of dosimetrists. METHODS: Fully automated re-planning was performed on twenty liver cancer patients, automated plans based on automated SBRT planning (ASP) program and manual plans were conducted and compared. One patient was randomly selected and evaluate the repeatability of ASP, ten automated and ten manual SBRT plans were generated based on the same initial optimization objectives. Then, ten SBRT plans were generated for another selected randomly patient with different initial optimization objectives to assess the reproducibility. All plans were clinically evaluated in a double-blinded manner by five experienced radiation oncologists. RESULTS: Fully automated plans provided similar planning target volume dose coverage and statistically better organ at risk sparing compared to the manual plans. Notably, automated plans achieved significant dose reduction in spinal cord, stomach, kidney, duodenum, and colon, with a median dose of D2% reduction ranging from 0.64 to 2.85 Gy. R50% and Dmean of ten rings for automated plans were significantly lower than those of manual plans. The average planning time for automated and manual plans was 59.8 ± 7.9 min vs. 127.1 ± 16.8 min (- 67.3 min). CONCLUSION: Automated planning for SBRT, without relying on historical data, can generate comparable or even better plan quality for liver cancer compared with manual planning, along with better reproducibility, and less clinically planning time.

BMI trajectories in late middle age, genetic risk, and the incident diabetes in older adults: evidence from a 26-year longitudinal study.

This study investigated the association between BMI trajectories in late middle age and incident diabetes in later years. A total of 11,441 participants aged 50-60 years from the Health and Retirement Study with at least two self-reported BMI records were included. Individual BMI trajectories representing average BMI changes per year were generated using multilevel modeling. Adjusted risk ratios (ARRs) and 95% confidence intervals (95% CIs) were calculated. Associations between BMI trajectories and diabetes risk in participants with different genetic risks were estimated for 5720 participants of European ancestry. BMI trajectories were significantly associated with diabetes risk in older age (slowly increasing vs. stable: ARR 1.31, 95% CI 1.12-1.54; rapidly increasing vs. stable: ARR 1.5, 95% CI 1.25-1.79). This association was strongest for normal-initial-BMI participants (slowly increasing: ARR 1.34, 95% CI 0.96-1.88; rapidly increasing: ARR 2.06, 95% CI 1.37-3.11). Participants with a higher genetic liability to diabetes and a rapidly increasing BMI trajectory had the highest risk for diabetes (ARR 2.15, 95% CI 1.67-2.76). These findings confirmed that BMI is the leading risk factor for diabetes and that although the normal BMI group has the lowest incidence rate for diabetes, people with normal BMI are most sensitive to changes in BMI.

Hepatitis B virus infection: An insight into the clinical connection and molecular interaction between hepatitis B virus and host extrahepatic cancer risk.

The evidence for chronic hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC) occurrence is well established. The hepatocyte epithelium carcinogenesis caused by HBV has been investigated and reviewed in depth. Nevertheless, recent findings from preclinical and observational studies suggested that chronic HBV infection is equally important in extrahepatic cancer occurrence and survival, specifically gastrointestinal system-derived cancers. Immune microenvironment changes (immune-suppressive cytokine infiltration), epigenetic modification (N6-methyladenosine), molecular signaling pathways (PI3K-Akt and Wnt), and serum biomarkers such as hepatitis B virus X (HBx) protein are potential underlying mechanisms in chronic HBV infection-induced extrahepatic cancers. This narrative review aimed to comprehensively summarize the most recent advances in evaluating the association between chronic HBV infection and extrahepatic cancer risk and explore the potential underlying molecular mechanisms in the carcinogenesis induction of extrahepatic cancers in chronic HBV conditions.

Depression Trajectories, Genetic Risk, and Cognitive Performance in Older Adults: Multilevel Model with a 10-Year Longitudinal Cohort.

INTRODUCTION: Cognitive performance in older ages is strongly affected by individuals' genetic predispositions. We investigated whether depression trajectories were associated with subsequent cognitive performance independent of participants' genetic predispositions. METHODS: Participants from the Health and Retirement Study with European ancestry and aged over 50 were included in the analysis. Depressive symptoms were evaluated using the Center for Epidemiologic Studies Depression Scale, and the 6-year trajectories were fitted using latent class linear mixed models. Linear multilevel regression was applied to model the associations between depression trajectory and subsequent cognitive performance. Stratified analyses were performed to investigate these associations in participants with different genetic predispositions of cognitive performance and APOE ε4 allelic status. RESULTS: A total of 5,942 eligible participants were included in the study. Four depression trajectories were identified. Compared with the nondepression trajectory, all other depression trajectories were associated with worse cognitive performance (ß [95% CI]: mild-depression trajectory: -0.20 [-0.56, -0.06], p = 0.007; worsening-depression trajectory: -0.29 [-0.47, -0.12], p = 0.001; persistent-depression trajectory: -0.32 [-0.53, -0.13], p = 0.001). Although these associations were independent of participants' inherent genetic risk, the participants with a low polygenetic score for cognitive performance were more likely to have an enhanced association between depression trajectories and cognitive decline. Similar relationships were also found in APOE ε4 noncarriers. CONCLUSION: Among older participants with European ancestry, even a mild-depression trajectory was associated with worse cognitive performance. Early intervention in participants with any degree of depression might benefit regarding preventing cognitive performance decline.

Association between Statin Use and Survival in Cancer Patients with Brain Metastasis: Retrospective Analysis from the Chinese Population.

Brain metastasis predicts a worse clinical outcome in cancer patients. Emerging observational evidence suggests that statin use has a protective role in overall cancer prevention. Whether statin use could also be a supplementary treatment for advanced-stage cancers remains under researched and controversial. Data for cancer patients with brain metastasis were selected from the linked electronic medical care records of the West China Hospital between October 2010 and July 2019. Fisher's exact chi-square test was used to compare the differences between cohorts. Multivariate Cox analysis was conducted to adjust the potential confounders in evaluating the role of statin use in the overall survival (OS) of cancer patients with brain metastasis. There were 4510 brain metastatic patients included in this retrospective study. The overall statin use rate in our patients was 5.28% (219 cases/4510 cases). Compared with the non-statin use cohort, patients who received statin therapy showed a decreased Karnofsky performance score (KPS, p < 0.001) and lower high-density lipoprotein (HDL, p = 0.020) but higher body mass index (BMI, p = 0.002) and triglyceride (TG, p < 0.001) at admission. There was no association between statin use and the OS of the cancer patients with brain metastasis (Hazard ratio (HR) = 0.90, 95% confidence interval (CI): 0.73−1.07, p = 0.213) during the univariate analysis. However, after adjusting for baseline patient characteristics, metabolism indicators, and cancer-specific factors, statin use was shown to have a significant protective role, aiding the survival of the cancer patients with brain metastasis (adjustHR = 0.82, 95%CI: 0.69−0.99, p = 0.034). Our results highlight that statin use shows significant survival benefits in cancer patients with brain metastasis. However, future research is needed to validate our findings.

Survival outcomes following treatment delays among patients with early-stage female cancers: a nationwide study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) severely hindered the timely receipt of health care for patients with cancer, especially female patients. Depression and anxiety were more pronounced in female patients than their male counterparts with cancer during treatment wait-time intervals. Herein, investigating the impact of treatment delays on the survival outcomes of female patients with early-stage cancers can enhance the rational and precise clinical decisions of physicians. METHODS: We analyzed five types of cancers in women from the Surveillance, Epidemiology, and End Results (SEER) program between Jan 2010 and Dec 2015. Univariate and multivariate Cox regression analyses were used to determine the impacts of treatment delays on the overall survival (OS) and cancer-specific survival (CSS) of the patients. RESULTS: A total of 241,661 females with early-stage cancer were analyzed (12,617 cases of non-small cell lung cancer (NSCLC), 166,051 cases of infiltrating breast cancer, 31,096 cases of differentiated thyroid cancer, 23,550 cases of colorectal cancer, and 8347 cases of cervical cancer). Worse OS rates were observed in patients with treatment delays ≥ 3 months in stage I NSCLC (adjustedHazard ratio (HR) = 1.11, 95% Confidence Interval (CI): 1.01-1.23, p = 0.044) and stage I infiltrating breast cancer (adjustedHR = 1.23, 95% CI 1.11-1.37, p < 0.001). When the treatment delay intervals were analyzed as continuous variables, similar results were observed in patients with stage I NSCLC (adjustedHR = 1.04, 95% CI 1.01-1.06, p = 0.010) and in those with stage I breast cancer (adjustedHR = 1.03, 95% CI 1.00-1.06, p = 0.029). However, treatment delays did not reduce the OS of patients with differentiated thyroid cancer, cervical cancer, or colorectal cancer in the early-stage. Only intermediate treatment delays impaired the CSS of patients with cervical cancer in stage I (adjustedHR = 1.31, 95% CI 1.02-1.68, p = 0.032). CONCLUSION: After adjusting for confounders, the prolonged time from diagnosis to the initiation of treatment (< 6 months) showed limited negative effects on the survival of most of the patients with early-stage female cancers. Whether our findings serve as evidence supporting the treatment deferral decisions of clinicians for patients with different cancers in resource-limited situations needs further validation.

Standard or extended STUPP? Optimal duration of temozolomide for patients with high-grade gliomas: a retrospective analysis.

PURPOSE: Brain radiotherapy combined with concomitant and six cycles of adjuvant temozolomide (TMZ) is the standard treatment for newly diagnosed high-grade gliomas (HGGs). However, the optimal number of cycles of TMZ is still controversial. We conducted this retrospective cohort study to evaluate whether prolonging adjuvant TMZ beyond six cycles resulted in better survival outcomes. METHODS: Patients with high-grade gliomas treated with standard brain radiotherapy combined with TMZ were retrospectively analysed. The duration of adjuvant TMZ ranged from 6 to 12 cycles. Those with 6 cycles of adjuvant TMZ were defined as the standard STUPP group, and those with 7-12 cycles were called the extended STUPP group. Median progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method. The Cox proportional hazards model was adopted to estimate the Hazard ratio (HR) associated with PFS and OS. RESULTS: From September 2011 to May 2021, 372 patients were eligible (143 in the standard group, 229 in the extended group). Patients who received extended STUPP had better PFS and OS compared with standard STUPP. The median PFS for the standard STUPP group was 12 months and for the extended STUPP group 22 months (log-rank P < 0.001). The median OS for the standard STUPP group and extended STUPP group were 12 months and 36 months, respectively (log-rank P < 0.001). In the subgroup analysis, the two treatments did not differ in IDH-mutated patients, while patients with IDH wild-type had a significantly better response to extended treatment than to standard treatment (PFS: log-rank P = 0.004; OS log-rank P = 0.001). Patients with MGMT promoter methylation treated with extended STUPP obtained longer PFS and OS than those treated with standard STUPP (PFS: log-rank P = 0.015; OS log-rank P = 0.010). Adverse events including leukopenia (P < 0.001), thrombocytopenia (P = 0.090), fatigue (P < 0.001) and nausea/vomiting (P = 0.004) were more frequent in the extended group. CONCLUSION: Extended TMZ treatment was superior to standard 6-cycle TMZ for both PFS and OS. The incidence of toxicities in extended group was higher but tolerable.

Comparison of Second-Line Treatments for Patients with Platinum-Resistant Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: A Systematic Review and Bayesian Network Meta-Analysis.

Several new drugs and combination strategies can be used to treat patients with recurrent or metastatic head and neck squamous cell carcinoma in the second-line treatment. Questions regarding the relative efficacy and safety of any two of the multiple second-line treatment strategies have emerged. This study aims to compare second-line treatments for patients with platinum-resistant recurrent or metastatic head and neck squamous cell carcinoma. Medline, Embase, and the Cochrane Central Register of Controlled Trials were searched to identify relevant articles. Direct and indirect evidence in terms of the objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and treatment-related adverse events grade ≥ 3 (grade ≥ 3 trAE) were analyzed in this Bayesian network meta-analysis. A total of twenty-three trials involving 5039 patients were included. These studies compared 20 different treatments, including the standard of care (SOC: docetaxel, methotrexate, or cetuximab), PD-1 inhibitors (nivolumab or pembrolizumab), durvalumab, tremelimumab, durvalumab + tremelimumab, palbociclib + SOC, tivantinib + SOC, sorafenib + SOC, EMD1201081 + SOC, vandetanib + SOC, PX-866 + SOC, 5-fluorouracil + SOC, cixutumumab + SOC, gefitinib + SOC, cabazitaxel, nolatrexed, duligotuzumab, zalutumumab, gefitinib, and afatinib. Among the currently available treatment options, compared to the standard of care (SOC: docetaxel, methotrexate, or cetuximab), the PD inhibitor significantly improved OS, ORR, and grade ≥ 3 trAE. Afatinib presented a better PFS and ORR than the SOC. Compared with afatinib, the PD-1 inhibitor had a better OS but a worse PFS. In conclusion, compared to the SOC, the PD-1 inhibitor significantly improved the OS, ORR, and grade ≥ 3 trAE. Afatinib presented a better PFS and ORR than the SOC. Compared with afatinib, the PD-1 inhibitor had a better OS but a worse PFS.

Induction versus adjuvant chemotherapy combined with concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma: a retrospective cohort study.

BACKGROUND: Currently available evidence favors the combination of chemotherapy with concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma (LANPC). However, the optimal timing for additional chemotherapy is unclear. This study was conducted to compare the efficacy and toxicity of induction chemotherapy plus concurrent chemoradiotherapy (IC+CCRT) versus concurrent chemoradiotherapy plus adjuvant chemotherapy (CCRT+AC). METHODS: Two medical centers in China enrolled patients with LANPC (stage III-IVB) between January 2009 and May 2020. Through the use of propensity score matching (PSM), baseline characteristics were balanced. The primary endpoint was overall survival (OS), which was evaluated by the Kaplan-Meier method and log-rank test. Potential independent prognostic factors were identified using univariate and multivariate Cox proportional hazard analyses. Based on the chi-squared test, we compared the adverse events associated with treatment between the groups. RESULTS: After the implementation of PSM, 159 patients treated with IC+CCRT and 72 patients treated with CCRT+AC were eventually enrolled in this study. There was no significant difference between patients treated with IC+CCRT and CCRT+AC in terms of 3-year OS (94.7% versus 90.9%, p=0.816), progression-free survival (PFS) (91.2% versus 83.1%, p=0.588), locoregional recurrence-free survival (LRFS) (92.5% versus 81.8%, p=0.478), or distant metastasis-free survival (DMFS) (93.4% versus 88.2%, p=0.783). There was no prognostic significance of the treatment for OS, PFS, LRFS, or DMFS (all p > 0.05) in the univariate and multivariate analyses. Patients treated with CCRT+AC had a higher incidence of grade 3 to 4 leucopenia (p=0.001) and neutropenia (p=0.001) than those treated with IC+CCRT. CONCLUSIONS: IC plus CCRT achieved comparable survival outcomes to CCRT plus AC and had a lower incidence of toxicity.

CT-Only Radiotherapy: An Exploratory Study for Automatic Dose Prediction on Rectal Cancer Patients Via Deep Adversarial Network.

Purpose: Current deep learning methods for dose prediction require manual delineations of planning target volume (PTV) and organs at risk (OARs) besides the original CT images. Perceiving the time cost of manual contour delineation, we expect to explore the feasibility of accelerating the radiotherapy planning by leveraging only the CT images to produce high-quality dose distribution maps while generating the contour information automatically. Materials and Methods: We developed a generative adversarial network (GAN) with multi-task learning (MTL) strategy to produce accurate dose distribution maps without manually delineated contours. To balance the relative importance of each task (i.e., the primary dose prediction task and the auxiliary tumor segmentation task), a multi-task loss function was employed. Our model was trained, validated and evaluated on a cohort of 130 rectal cancer patients. Results: Experimental results manifest the feasibility and improvements of our contour-free method. Compared to other mainstream methods (i.e., U-net, DeepLabV3+, DoseNet, and GAN), the proposed method produces the leading performance with statistically significant improvements by achieving the highest HI of 1.023 (3.27E-5) and the lowest prediction error with ΔD95 of 0.125 (0.035) and ΔDmean of 0.023 (4.19E-4), respectively. The DVH differences between the predicted dose and the ideal dose are subtle and the errors in the difference maps are minimal. In addition, we conducted the ablation study to validate the effectiveness of each module. Furthermore, the results of attention maps also prove that our CT-only prediction model is capable of paying attention to both the target tumor (i.e., high dose distribution area) and the surrounding healthy tissues (i.e., low dose distribution areas). Conclusion: The proposed CT-only dose prediction framework is capable of producing acceptable dose maps and reducing the time and labor for manual delineation, thus having great clinical potential in providing accurate and accelerated radiotherapy. Code is available at https://github.com/joegit-code/DoseWithCT.

Treatment plan comparison of volumetric-modulated arc therapy to intensity-modulated radiotherapy in lung stereotactic body radiotherapy using either 6- or 10-MV photon energies.

PURPOSE: The aim of this study was to dosimetrically compare volumetric-modulated arc therapy (VMAT) with intensity-modulated radiotherapy (IMRT) techniques using either 6- or 10-MV photon beam energies in lung stereotactic body radiation therapy (SBRT) plans. METHODS: Thirty patients with primary or metastatic lung tumors eligible for SBRT were randomly selected. VMAT and IMRT treatment plans using either 6- or 10-MV photon energies were generated through automatic SBRT planning software in the RayStation treatment planning system. RESULTS: For planning target volume, there was no difference in D95% for all plans, whereas D2% and D50% were significantly increased by 5.22%-5.98% and 2.47%-2.59%, respectively, using VMAT6/10-MV plans compared to IMRT6/10-MV plans. When comparing the Dmax of organs at risk (OARs), VMAT6/10-MV was 18.32%-47.95% lower than IMRT6/10-MV for almost all OARs. VMAT6/10-MV obviously decreased Dmean , V5Gy , V10Gy , and V20Gy of whole lung by 9.68%-20.92% than IMRT6/10-MV . Similar results were found when comparing VMAT6-MV with IMRT10-MV or VMAT10-MV with IMRT6-MV . The differences in the D2% , heterogeneity index, and conformity index between 6- and 10-MV plans are not statistically significant. Plans using 6-MV performed 4.68%-8.91% lower levels of Dmax of spinal cord, esophagus, great vessels, and trachea and proximal bronchial tree than those using 10-MV plans. Similarly, Dmean , V5Gy , V10Gy , and V20Gy of whole lung were also reduced by 2.79%-5.25% using 6-MV. For dose fall-off analysis, the D2cm and R50% of VMAT6/10-MV were lower than those of IMRT6/10-MV . Dose fall-off curve based on 10 rings was steeper for VMAT plans than IMRT plans regardless of the energy used. CONCLUSIONS: For lung SBRT plans, VMAT-based plans significantly reduced OARs dose and steepened dose fall-off curves compared to IMRT-based plans. A 6-MV energy level was a better choice than 10-MV for lung SBRT. In addition, the dose differences between different techniques were more obvious than those between different energy levels.

The Development and Validation of a Nomogram Incorporating Clinical, Pathological, and Therapeutic Features to Predict Overall Survival in Patients With Penile Cancer: A SEER-Based Study.

Objective: This study aimed to investigate the prognostic factors of penile cancer and establish a comprehensive predictive model for clinical application. Methods: A total of 581 patients from the Surveillance, Epidemiology, and End Results (SEER) program (2000-2018) were used to develop the prognostic model. The multivariate Cox proportional hazards regression was performed to identify independent prognostic factors to develop the nomogram. The performance of this model was validated internally by a cohort with 143 patients from the SEER database and validated externally by a cohort with 70 patients from the West China Hospital, Sichuan University (2010-2020). Results: Age, marital status, size of the primary lesion, primary tumor (T), regional lymph nodes status, distant metastasis (M), and the surgery of regional lymph node (LND) were the independent prognostic factors for overall survival (OS) and were incorporated in the prognostic model. The prognostic nomogram showed a good risk stratification ability for OS in the development cohort, internal validation cohort, and external validation cohort. Conclusion: This study incorporates the clinical, pathological, and therapeutic features comprehensively to develop a novel and clinically effective prognostic model for patients with penile cancer.