Different trends of gastric cancer in China, Japan, Republic of Korea and United States of America.

Gastric cancer exerts a significant healthcare burden worldwide and is highly geographically heterogeneous. This study investigates the burden of gastric cancer in China from 1990 to 2019 and compares it with Japan, South Korea, and the United States. The results indicated a declining trend in ASIR and ASDR in four countries. However, the incidence and death rates in China remain disproportionately high. Significant gender disparities exist in the incidence and death rates, with males experiencing significantly higher rates than females. Incidence and death rates were found to increase with age in all studied countries. In China, a transient upward trend was observed in the period effect, whereas the cohort effect has been declining. In contrast, the remaining countries showed decreasing patterns in both period and cohort effects. The burden of disease remains high in China, therefore, broaden the scope of gastroscopy screening and concentrate on high-risk groups is vital.

Partial response to trastuzumab deruxtecan (DS8201) following progression in HER2-amplified breast cancer with pulmonary metastases managed with disitamab vedotin (RC48): a comprehensive case report and literature review.

Breast cancer remains one of the predominant malignancies worldwide. In the context of inoperable advanced or metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer, systemic management primarily relies on HER2-targeting monoclonal antibodies. With the successful development of anti-HER2 antibody-drug conjugates (ADCs), these agents have been increasingly integrated into therapeutic regimens for metastatic breast cancer. Here, we present the case of a 42-year-old female patient with HER2-positive pulmonary metastatic breast cancer who underwent an extensive treatment protocol. This protocol included chemotherapy, radiation therapy, hormonal therapy, surgical intervention on the breast, and anti-HER2 therapies. The anti-HER2 therapies involved both singular and dual targeting strategies using trastuzumab and the ADC disitamab vedotin (RC48) over an 8-year period. After experiencing disease progression following HER2-targeted therapy with RC48, the patient achieved noticeable partial remission through a therapeutic regimen that combined trastuzumab deruxtecan (DS8201) and tislelizumab. The data suggest a promising role for DS8201 in managing advanced stages of HER2-amplified metastatic breast cancer, especially in cases that demonstrate progression after initial HER2-directed therapies using ADCs. Furthermore, its combination with anti-PD-1 agents enhances therapeutic efficacy by augmenting the anti-tumoral immune response.

Developing an optimal stratification model for colorectal cancer screening and reducing racial disparities in multi-center population-based studies.

BACKGROUND: Early detection of colorectal neoplasms can reduce the colorectal cancer (CRC) burden by timely intervention for high-risk individuals. However, effective risk prediction models are lacking for personalized CRC early screening in East Asian (EAS) population. We aimed to develop, validate, and optimize a comprehensive risk prediction model across all stages of the dynamic adenoma-carcinoma sequence in EAS population. METHODS: To develop precision risk-stratification and intervention strategies, we developed three trans-ancestry PRSs targeting colorectal neoplasms: (1) using 148 previously identified CRC risk loci (PRS148); (2) SNPs selection from large-scale meta-analysis data by clumping and thresholding (PRS183); (3) PRS-CSx, a Bayesian approach for genome-wide risk prediction (PRSGenomewide). Then, the performance of each PRS was assessed and validated in two independent cross-sectional screening sets, including 4600 patients with advanced colorectal neoplasm, 4495 patients with non-advanced adenoma, and 21,199 normal individuals from the ZJCRC (Zhejiang colorectal cancer set; EAS) and PLCO (the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial; European, EUR) studies. The optimal PRS was further incorporated with lifestyle factors to stratify individual risk and ultimately tested in the PLCO and UK Biobank prospective cohorts, totaling 350,013 participants. RESULTS: Three trans-ancestry PRSs achieved moderately improved predictive performance in EAS compared to EUR populations. Remarkably, the PRSs effectively facilitated a thorough risk assessment across all stages of the dynamic adenoma-carcinoma sequence. Among these models, PRS183 demonstrated the optimal discriminatory ability in both EAS and EUR validation datasets, particularly for individuals at risk of colorectal neoplasms. Using two large-scale and independent prospective cohorts, we further confirmed a significant dose-response effect of PRS183 on incident colorectal neoplasms. Incorporating PRS183 with lifestyle factors into a comprehensive strategy improves risk stratification and discriminatory accuracy compared to using PRS or lifestyle factors separately. This comprehensive risk-stratified model shows potential in addressing missed diagnoses in screening tests (best NPV = 0.93), while moderately reducing unnecessary screening (best PPV = 0.32). CONCLUSIONS: Our comprehensive risk-stratified model in population-based CRC screening trials represents a promising advancement in personalized risk assessment, facilitating tailored CRC screening in the EAS population. This approach enhances the transferability of PRSs across ancestries and thereby helps address health disparity.

Targeting O-GlcNAcylation in cancer therapeutic resistance: The sugar Saga continues.

O-linked-N-acetylglucosaminylation (O-GlcNAcylation), a dynamic post-translational modification (PTM), holds profound implications in controlling various cellular processes such as cell signaling, metabolism, and epigenetic regulation that influence cancer progression and therapeutic resistance. From the therapeutic perspective, O-GlcNAc modulates drug efflux, targeting and metabolism. By integrating signals from glucose, lipid, amino acid, and nucleotide metabolic pathways, O-GlcNAc acts as a nutrient sensor and transmits signals to exerts its function on genome stability, epithelial-mesenchymal transition (EMT), cell stemness, cell apoptosis, autophagy, cell cycle. O-GlcNAc also attends to tumor microenvironment (TME) and the immune response. At present, several strategies aiming at targeting O-GlcNAcylation are under mostly preclinical evaluation, where the newly developed O-GlcNAcylation inhibitors markedly enhance therapeutic efficacy. Here we systematically outline the mechanisms through which O-GlcNAcylation influences therapy resistance and deliberate on the prospects and challenges associated with targeting O-GlcNAcylation in future cancer treatments.

Prioritization of risk genes in colorectal cancer by integrative analysis of multi-omics data and gene networks.

Genome-wide association studies (GWASs) have identified over 140 colorectal cancer (CRC)-associated loci; however, target genes at the majority of loci and underlying molecular mechanisms are poorly understood. Here, we utilized a Bayesian approach, integrative risk gene selector (iRIGS), to prioritize risk genes at CRC GWAS loci by integrating multi-omics data. As a result, a total of 105 high-confidence risk genes (HRGs) were identified, which exhibited strong gene dependencies for CRC and enrichment in the biological processes implicated in CRC. Among the 105 HRGs, CEBPB, located at the 20q13.13 locus, acted as a transcription factor playing critical roles in cancer. Our subsequent assays indicated the tumor promoter function of CEBPB that facilitated CRC cell proliferation by regulating multiple oncogenic pathways such as MAPK, PI3K-Akt, and Ras signaling. Next, by integrating a fine-mapping analysis and three independent case-control studies in Chinese populations consisting of 8,039 cases and 12,775 controls, we elucidated that rs1810503, a putative functional variant regulating CEBPB, was associated with CRC risk (OR=0.90, 95%CI=0.86-0.93, P=1.07×10-7). The association between rs1810503 and CRC risk was further validated in three additional multi-ancestry populations consisting of 24,254 cases and 58,741 controls. Mechanistically, the rs1810503 A to T allele change weakened the enhancer activity in an allele-specific manner to decrease CEBPB expression via long-range promoter-enhancer interactions, mediated by the transcription factor, REST, and thus decreased CRC risk. In summary, our study provides a genetic resource and a generalizable strategy for CRC etiology investigation, and highlights the biological implications of CEBPB in CRC tumorigenesis, shedding new light on the etiology of CRC.

Deep-learning-driven dose prediction and verification for stereotactic radiosurgical treatment of isolated brain metastases.

Purpose: While deep learning has shown promise for automated radiotherapy planning, its application to the specific scenario of stereotactic radiosurgery (SRS) for brain metastases using fixed-field intensity modulated radiation therapy (IMRT) on a linear accelerator remains limited. This work aimed to develop and verify a deep learning-guided automated planning protocol tailored for this scenario. Methods: We collected 70 SRS plans for solitary brain metastases, of which 36 cases were for training and 34 for testing. Test cases were derived from two distinct clinical institutions. The envisioned automated planning process comprised (1): clinical dose prediction facilitated by deep-learning algorithms (2); transformation of the forecasted dose into executable plans via voxel-centric dose emulation (3); validation of the envisaged plan employing a precise dosimeter in conjunction with a linear accelerator. Dose prediction paradigms were established by engineering and refining two three-dimensional UNet architectures (UNet and AttUNet). Input parameters encompassed computed tomography scans from clinical plans and demarcations of the focal point alongside organs at potential risk (OARs); the ensuing output manifested as a 3D dose matrix tailored for each case under scrutiny. Results: Dose estimations rendered by both models mirrored the manual plans and adhered to clinical stipulations. As projected by the dual models, the apex and average doses for OARs did not deviate appreciably from those delineated in the manual plan (P-value≥0.05). AttUNet showed promising results compared to the foundational UNet. Predicted doses showcased a pronounced dose gradient, with peak concentrations localized within the target vicinity. The executable plans conformed to clinical dosimetric benchmarks and aligned with their associated verification assessments (100% gamma approval rate at 3 mm/3%). Conclusion: This study demonstrates an automated planning technique for fixed-field IMRT-based SRS for brain metastases. The envisaged plans met clinical requirements, were reproducible across centers, and achievable in deliveries. This represents progress toward automated paradigms for this specific scenario.

Single-cell and bulk RNA sequencing analysis of B cell marker genes in TNBC TME landscape and immunotherapy.

Objective: This study amied to investigate the prognostic characteristics of triple negative breast cancer (TNBC) patients by analyzing B cell marker genes based on single-cell and bulk RNA sequencing. Methods: Utilizing single-cell sequencing data from TNBC patients, we examined tumor-associated B cell marker genes. Transcriptomic data from The Cancer Genome Atlas (TCGA) database were used as the foundation for predictive modeling. Independent validation set was conducted using the GSE58812 dataset. Immune cell infiltration into the tumor was assessed through various, including XCELL, TIMER, QUANTISEQ, CIBERSORT, CIBERSORT-ABS, and ssGSEA. The TIDE score was utilized to predict immunotherapy outcomes. Additional investigations were conducted on the immune checkpoint blockade gene, tumor mutational load, and the GSEA enrichment analysis. Results: Our analysis encompassed 22,106 cells and 20,556 genes in cancerous tissue samples from four TNBC patients, resulting in the identification of 116 B cell marker genes. A B cell marker gene score (BCMG score) involving nine B cell marker genes (ZBP1, SEL1L3, CCND2, TNFRSF13C, HSPA6, PLPP5, CXCR4, GZMB, and CCDC50) was developed using TCGA transcriptomic data, revealing statistically significant differences in survival analysis (P<0.05). Functional analysis demonstrated that marker genes were predominantly associated with immune-related pathways. Notably, substantial differences between the higher and lower- BCMG score groups were observed in terms of immune cell infiltration, immune cell activity, tumor mutational burden, TIDE score, and the expression of immune checkpoint blockade genes. Conclusion: This study has established a robust model based on B-cell marker genes in TNBC, which holds significant potential for predicting prognosis and response to immunotherapy in TNBC patients.

New treatment insights into pancreatic acinar cell carcinoma: case report and literature review.

Pancreatic acinar cell carcinoma (PACC) is a rare pancreatic malignancy with unique clinical, molecular, and morphologic features. The long-term survival of patients with PACC is substantially better than that of patients with ductal adenocarcinoma of the pancreas. Surgical resection is considered the first choice for treatment; however, there is no standard treatment option for patients with inoperable disease. The patient with metastatic PACC reported herein survived for more than 5 years with various treatments including chemotherapy, radiotherapy, antiangiogenic therapy and combined immunotherapy.

Dosimetric impact of hollow intraoral stents for head and neck cancer radiotherapy: A phantom study.

PURPOSE: To investigate the dosimetric impact of the calculation boundaries and dose calculation algorithms of radiotherapy in head and neck cancer patients with an opened oral cavity connected to the exterior by a hollow intraoral positioning stent. METHODS AND MATERIALS: A homemade silicone phantom with an opened oral cavity was placed in a CIRS head phantom to model head and neck cancer patients with a hollow intraoral positioning stent. 3D-CRT plans were designed on CT images of the phantom in Monaco and Pinnacle3 treatment planning systems (TPSs) with the same beam parameters. The default boundary and manually extrapolated boundary were both adopted in these two TPSs to explore the dosimetric impact on treatment plans. The nanoDot™ optically stimulated luminescence dosimeters (OSLDs) were chosen to measure the planned dose surrounding the oral cavity of the head phantom after calibration. RESULT: The doses in the air cavity and two measuring points at the joint area were dramatically changed from 0.0, 92.4 and 148.8 cGy to 177.8, 244.2 and 244.1 cGy in Monaco after adopting the extrapolated boundary. While the calculated doses at the same place were changed from 61.2, 143.7 and 198.3 cGy to 175.4, 234.7 and 233.2 cGy in Pinnacle3 with a similar calculation boundary. For the Monaco TPS, the relative errors compared to the OSLD measured doses were 2.94 ± 1.93%, 0.53 ± 8.64%, 2.65 ± 1.87% and 3.93 ± 1.69% at 4 measuring positions. In contrast, the relative errors 4.03 ± 1.93%, 4.85 ± 8.64%, 7.61 ± 1.87% and 5.61 ± 1.69% were observed in Pinnacle3 . CONCLUSION: The boundary setting of an opened oral cavity in TPSs has a significant dosimetric impact on head and neck cancer radiotherapy. An extrapolated boundary should be manually set up to include the whole oral cavity in the dose calculation domain to avoid major dose deviations.

Bre1/RNF20 promotes Rad51-mediated strand exchange and antagonizes the Srs2/FBH1 helicases.

Central to homologous recombination (HR) is the assembly of Rad51 recombinase on single-strand DNA (ssDNA), forming the Rad51-ssDNA filament. How the Rad51 filament is efficiently established and sustained remains partially understood. Here, we find that the yeast ubiquitin ligase Bre1 and its human homolog RNF20, a tumor suppressor, function as recombination mediators, promoting Rad51 filament formation and subsequent reactions via multiple mechanisms independent of their ligase activities. We show that Bre1/RNF20 interacts with Rad51, directs Rad51 to ssDNA, and facilitates Rad51-ssDNA filament assembly and strand exchange in vitro. In parallel, Bre1/RNF20 interacts with the Srs2 or FBH1 helicase to counteract their disrupting effect on the Rad51 filament. We demonstrate that the above functions of Bre1/RNF20 contribute to HR repair in cells in a manner additive to the mediator protein Rad52 in yeast or BRCA2 in human. Thus, Bre1/RNF20 provides an additional layer of mechanism to directly control Rad51 filament dynamics.

Effect of radiotherapy interruption on nasopharyngeal cancer.

Nasopharyngeal carcinoma (NPC) is a malignant tumor originating from the epithelial cells of the nasopharynx with a unique geographic distribution, and is particularly prevalent in East and Southeast Asia. Due to its anatomical location, the surgery is difficult to access and the high sensitivity of nasopharyngeal cancer to radiotherapy (RT) makes it the main treatment modality. Radical radiotherapy is the first-line treatment for early-stage nasopharyngeal carcinoma and the cornerstone of multidisciplinary treatment for patients with locally advanced nasopharyngeal carcinoma. Nevertheless, radiotherapy interruption is inevitable as a consequence of unavoidable factors such as public holidays, machine malfunction, patient compliance, and adverse response to treatment, which in turn leads to a reduction in bioactivity and causes sublethal loss of tumor cells to repair. Unirradiated tumor cells are more likely to repopulate at or near their original fastest growth rate during this interval. If no measures are taken after the radiotherapy interruption, such as increasing the dose of radiotherapy and systemic therapy, the tumor is most likely to go uncontrolled and then progress. This review describes the effects of radiotherapy interruption on nasopharyngeal carcinoma, the mechanism of the effect, and explores the measures that can be taken in response to such interruption.

Biophysical cues to improve the immunomodulatory capacity of mesenchymal stem cells: The progress and mechanisms.

Mesenchymal stem cells (MSCs) can maintain immune homeostasis and many preclinical trials with MSCs have been carried out around the world. In vitro culture of MSCs has been found to result in the decline of immunomodulatory capacity, migration and proliferation. To address these problems, simulating the extracellular environment for preconditioning of MSCs is a promising and inexpensive method. Biophysical cues in the external environment that MSCs are exposed to have been shown to affect MSC migration, residency, differentiation, secretion, etc. We review the main ways in which MSCs exert their immunomodulatory ability, and summarize recent advances in mechanical preconditioning of MSCs to enhance immunomodulatory capacity and related mechanical signal sensing and transduction mechanisms.

Redox-associated messenger RNAs identify novel prognostic values and influence the tumor immune microenvironment of lung adenocarcinoma.

Background: An imbalance of redox homeostasis participates in tumorigenesis, proliferation, and metastasis, which results from the production of reactive oxygen species (ROS). However, the biological mechanism and prognostic significance of redox-associated messenger RNAs (ramRNAs) in lung adenocarcinoma (LUAD) still remain unclear. Methods: Transcriptional profiles and clinicopathological information were retrieved from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) of LUAD patients. A total of 31 overlapped ramRNAs were determined, and patients were separated into three subtypes by unsupervised consensus clustering. Biological functions and tumor immune-infiltrating levels were analyzed, and then, differentially expressed genes (DEGs) were identified. The TCGA cohort was divided into a training set and an internal validation set at a ratio of 6:4. Least absolute shrinkage and selection operator regression were used to compute the risk score and determine the risk cutoff in the training set. Both TCGA and GEO cohort were distinguished into a high-risk or low-risk group at the median cutoff, and then, relationships of mutation characteristics, tumor stemness, immune differences, and drug sensitivity were investigated. Results: Five optimal signatures (ANLN, HLA-DQA1, RHOV, TLR2, and TYMS) were selected. Patients in the high-risk group had poorer prognosis, higher tumor mutational burden, overexpression of PD-L1, and lower immune dysfunction and exclusion score compared with the low-risk group. Cisplatin, docetaxel, and gemcitabine had significantly lower IC50 in the high-risk group. Conclusion: This study constructed a novel predictive signature of LUAD based on redox-associated genes. Risk score based on ramRNAs served as a promising biomarker for prognosis, TME, and anti-cancer therapies of LUAD.

Inguinal nodal clinical target volume delineation based on analysis of anatomical locations of normal and metastatic lymph nodes in pelvic malignant tumors.

PURPOSE: To optimize inguinal nodal clinical target volume (CTV) delineation based on analysis of the anatomical locations and embryonic development of normal and metastatic inguinal lymph nodes (ILNs) in patients with pelvic malignant tumors, including cervical, vaginal, vulvar, and anal tumors. MATERIALS AND METHODS: One hundred and eighty-one patients with pelvic malignancies and 415 involved ILNs treated with intensity-modulated radiation therapy were selected. First, the inguinal nodal CTV was divided into three fields as follows: I, horizontal superficial inguinal field; II, vertical superficial inguinal field; and III, deep inguinal field. Initial CTV delineation of each field was based on analysis of the anatomical locations and embryonic development of normal ILNs. Subsequently, the positions of metastatic ILNs relative to the proper anatomical landmarks or vessels were determined to optimally delineate the final ILN CTV contours. Eighty percent of the data acquired (n = 145) were used as test data for optimization and analysis, the remaining 20% (n = 36) were used for delineation validation. RESULTS: In total, 252 positive ILNs in 103 cervical cancer patients, 94 positive ILNs in 41 vulvar cancer patients, 8 positive ILNs in 3 vaginal cancer patients, and 61 positive ILNs in 34 anal cancer patients were enrolled. Detailed target volume contouring guidelines for the three divisions were determined on images. All positive ILNs from the remaining 20% patients were located in the CTV boundaries delineated based on analysis of 80% of the data acquired. Importantly, the final inguinal nodal CTV field determined using our method was substantially smaller than defined by existing atlases, and the femoral vessels were excluded in the delineation. CONCLUSIONS: This study provided anatomical, embryonic, surgical, and statistical evidence to facilitate ILN CTV delineation in radiotherapy planning for patients with pelvic malignancies.

Radiotherapy Improves Survival of Patients With Lymphovascular Invasion in pT1b Esophageal Squamous Cell Cancer After Endoscopic Submucosal Dissection.

INTRODUCTION: Adjuvant radiotherapy is recommended for pT1b esophageal squamous cell cancer (ESCC) after endoscopic submucosal dissection (ESD). However, it is unclear whether additional radiotherapy can improve patient survival. This study aimed to evaluate the efficacy of adjuvant radiotherapy after ESD for pT1b ESCC. METHODS: This was a multicenter, cross-sectional study involving 11 hospitals in China. Between January 2010 and December 2019, patients with T1bN0M0 ESCC treated with or without adjuvant radiotherapy after ESD were included. Survival between groups was compared. RESULTS: Overall, 774 patients were screened, and 161 patients were included. Forty-seven patients (29.2%) received adjuvant radiotherapy after ESD (RT group) and 114 (70.8%) underwent ESD alone (non-RT group). There were no significant differences in overall survival (OS) and disease-free survival (DFS) between the RT and non-RT groups. Lymphovascular invasion (LVI) was the only prognostic factor. In the LVI+ group, adjuvant radiotherapy significantly improved survival (5-year OS: 91.7% vs 59.5%, P = 0.050; 5-year DFS: 92.9% vs 42.6%, P = 0.010). In the LVI- group, adjuvant radiotherapy did not improve survival (5-year OS: 83.5% vs 93.9%, P = 0.148; 5-year DFS: 84.2% vs 84.7%, P = 0.907). The standardized mortality ratios were 1.52 (95% confidence interval 0.04-8.45) in the LVI+ group with radiotherapy and 0.55 (95% confidence interval 0.15-1.42) in the LVI- group without radiotherapy. DISCUSSION: Adjuvant radiotherapy could improve survival in pT1b ESCC with LVI+ other than LVI- after ESD. Selective adjuvant radiotherapy based on LVI status achieved survival rates similar to those of the general population.

Design, synthesis and pharmacological evaluation of ß-carboline derivatives as potential antitumor agent via targeting autophagy.

A series of novel ß-carboline derivatives was designed, synthesized and evaluated as potential anticancer agents. Among them, compound 6g showed the most potent antiproliferative activity against the 786-0, HT-29 and 22RV1 cell lines with IC50 values of 2.71, 2.02, and 3.86 µM, respectively. The antitumor efficiency of compound 6gin vivo was also evaluated, and the results revealed that compound 6g significantly suppressed tumor development and reduced tumor weight in a mouse colorectal cancer homograft model. Further investigation on mechanisms of action demonstrated that compound 6g inhibited HCT116 cell growth by stimulating the ATG5/ATG7-dependent autophagic pathway. These molecules might be served as candidates for further development of colorectal cancer therapy agent.

Establishment and validation of a prognostic nomogram for extrahepatic cholangiocarcinoma.

Simple summary: Accurately estimate the prognosis of patients with ECCA is important. However, the TNM system has some limitations, such as low accuracy, exclusion of other factors (e.g., age and sex), and poor performance in predicting individual survival risk. In contrast, a nomogram-based clinical model related to a comprehensive analysis of all risk factors is intuitive and straightforward, facilitating the probabilistic analysis of tumor-related risk factors. Simultaneously, a nomogram can also effectively drive personalized medicine and facilitate clinicians for prognosis prediction. Therefore, we construct a novel practical nomogram and risk stratification system to predict CSS in patients with ECCA. Background: Accurately estimate the prognosis of patients with extrahepatic cholangiocarcinoma (ECCA) was important, but the existing staging system has limitations. The present study aimed to construct a novel practical nomogram and risk stratification system to predict cancer-specific survival (CSS) in ECCA patients. Methods: 3415 patients diagnosed with ECCA between 2010 and 2015 were selected from the SEER database and randomized into a training cohort and a validation cohort at 7:3. The nomogram was identified and calibrated using the C-index, receiver operating characteristic curve (ROC), and calibration plots. Decision curve analysis (DCA), net reclassification index (NRI), integrated discrimination improvement (IDI) and the risk stratification were used to compare the nomogram with the AJCC staging system. Results: Nine variables were selected to establish the nomogram. The C-index (training cohort:0.785; validation cohort:0.776) and time-dependent AUC (>0.7) showed satisfactory discrimination. The calibration plots also revealed that the nomogram was consistent with the actual observations. The NRI (training cohort: 1-, 2-, and 3-year CSS:0.27, 0.27,0.52; validation cohort:1-,2-,3-year CSS:0.48,0.13,0.34), IDI (training cohort: 1-, 2-, 3-year CSS:0.22,0.18,0.16; validation cohort: 1-,2-,3-year CSS:0.18,0.16,0.17), and DCA indicated that the established nomogram significantly outperformed the AJCC staging system (P<0.05) and had better recognition compared to the AJCC staging system. Conclusions: We developed a practical prognostic nomogram to help clinicians assess the prognosis of patients with ECCA.

Introduce a rotational robust optimization framework for spot-scanning proton arc (SPArc) therapy.

Objective. Proton dosimetric uncertainties resulting from the patient's daily setup errors in rotational directions exist even with advanced image-guided radiotherapy techniques. Thus, we developed a new rotational robust optimization SPArc algorithm (SPArcrot) to mitigate the dosimetric impact of the rotational setup error in Raystation ver. 6.02 (RaySearch Laboratory AB, Stockholm, Sweden).Approach.The initial planning CT was rotated ±5° simulating the worst-case setup error in the roll direction. The SPArcrotuses a multi-CT robust optimization framework by taking into account of such rotational setup errors. Five cases representing different disease sites were evaluated. Both SPArcoriginaland SPArcrotplans were generated using the same translational robust optimized parameters. To quantitatively investigate the mitigation effect from the rotational setup errors, all plans were recalculated using a series of pseudo-CT with rotational setup error (±1°/±2°/±3°/±5°). Dosimetric metrics such as D98% of CTV, and 3D gamma analysis were used to assess the dose distribution changes in the target and OARs.Main results.The magnitudes of dosimetric changes in the targets due to rotational setup error were significantly reduced by the SPArcrotcompared to SPArc in all cases. The uncertainties of the max dose to the OARs, such as brainstem, spinal cord and esophagus were significantly reduced using SPArcrot. The uncertainties of the mean dose to the OARs such as liver and oral cavity, parotid were comparable between the two planning techniques. The gamma passing rate (3%/3 mm) was significantly improved for CTV of all tumor sites through SPArcrot.Significance.Rotational setup error is one of the major issues which could lead to significant dose perturbations. SPArcrotplanning approach can consider such rotational error from patient setup or gantry rotation error by effectively mitigating the dose uncertainties to the target and in the adjunct series OARs.

Conversion therapy from unresectable stage IIIC non-small-cell lung cancer to radical surgery via anti-PD-1 immunotherapy combined with chemotherapy and anti-angiogenesis: A case report and literature review.

The prognosis of patients with stage IIIC non-small-cell lung cancer (NSCLC) is poor due to the loss of surgical treatment opportunities. Improving the prognosis of these patients with IIIC NSCLC urgently needs to be addressed. Here, we report a stage IIIC (T4N3M0 IIIC (AJCC 8th)) NSCLC patient treated with 2 cycles of anti-PD-1 immunotherapy combined with chemotherapy and anti-angiogenesis therapy; after two cycles of treatment, the patient achieved a partial response and obtained the opportunity for surgical treatment. After the operation, the patient achieved a pathological complete response and successfully transformed from unresectable stage IIIC lung cancer to radical surgery (ypT0N0M0). Our study is expected to provide new ideas for treating patients with unresectable stage IIIC NSCLC in the future.

Design, synthesis and mechanism of action of novel 1,9-disubstituted ß-carboline derivatives as antitumor agents.

A range of novel 1,9-disubstituted ß-carboline derivatives was designed, synthesized and evaluated as potential anticancer agents. The preliminary study suggested that compounds 6a, 6b, 6c, 6d, 6e, 6f, 6g, and 6h tested in this study exerted potent antiproliferative effects on ten selected human tumor cell lines, with compound 6e being the most effective antiproliferative agent against the BGC-823, A375 and HT-29 cell lines, with IC50 values of 23.9, 9.3, and 3.6 µM, respectively. In addition, the antitumor capability of compound 6e was also evaluated in vivo, which demonstrated that compound 6e distinctly inhibited colorectal tumor growth in syngeneic BALB/c mice. Further research into the fundamental mechanism revealed that compound 6e inhibited colorectal cancer growth through the ATG5 (autophagy-related-5)/ATG7 (autophagy-related-7)-dependent autophagy pathway. This research can contribute to further clinical application of ß-carboline derivatives as new antitumor drugs.