Myelodysplastic syndromes (MDS) are clonal hematologic malignancies characterized by ineffective hematopoiesis and dysplasia of the myeloid cell lineage and are characterized by peripheral blood cytopenia and an increased risk of transformation to acute myeloid leukemia (AML). Approximately half of the patients with MDS have somatic mutations in the spliceosome gene. Splicing Factor 3B Subunit 1A (SF3B1), the most frequently occurring splicing factor mutation in MDS is significantly associated with the MDS-RS subtype. SF3B1 mutations are intimately involved in the MDS regulation of various pathophysiological processes, including impaired erythropoiesis, dysregulated iron metabolism homeostasis, hyperinflammatory features, and R-loop accumulation. In the fifth edition of the World Health Organization (WHO) classification criteria for MDS, MDS with SF3B1 mutations has been classified as an independent subtype, which plays a crucial role in identifying the disease phenotype, promoting tumor development, determining clinical features, and influencing tumor prognosis. Given that SF3B1 has demonstrated therapeutic vulnerability both in early MDS drivers and downstream events, therapy based on spliceosome-associated mutations is considered a novel strategy worth exploring in the future.

Introduction: Circulating tumor-derived biomarkers can potentially impact cancer management throughout the continuum of care. This small exploratory study aimed to assess the relative levels of such biomarkers in the tumor-draining vascular beds in patients with solid tumors compared to levels in their peripheral veins.Methods: Using an endovascular image-guided approach, we obtained blood samples from peripheral veins and other vascular compartments–including the most proximal venous drainage from solid tumors–from a set of nine oncology patients with various primary and metastatic malignancies. We then interrogated these samples for a panel of oncological biomarkers, including circulating tumor cells (CTCs), exosome-derived microRNAs (miRNAs), circulating tumor DNA (ctDNA) mutations, and certain cancer-related proteins/biochemical markers.Results: We found substantially higher levels of CTCs, certain miRNAs, and specific ctDNA mutations in samples from vascular beds closer to the tumor compared with those from peripheral veins and also noted that some of these signals were altered by treatment procedures.Discussion: Our results indicate that tumor-proximal venous samples are highly enriched for some oncological biomarkers and may allow for more robust molecular analysis than peripheral vein samples.

Purpose: We prospectively investigated the acute toxicities focusing on skin and hematologic function in breast cancer patients who received hypofractionated whole breast irradiation with simultaneous integrated boost (HF-WBI-SIB) with helical tomotherapy (HT), with or without regional nodal irradiation (RNI).Methods: The dose of WBI and RNI was 42.4 Gy in 16 fractions. Tumor bed was prescribed to 49.6 Gy in 16 fractions simultaneously. The association between the worst grade of acute toxicities during treatment and receiving RNI was analyzed. The integral dose to the whole body between the two groups was also compared.Results: Between May 2021 and May 2022, 85 patients were enrolled; 61 patients received HF-WBI-SIB only (71.8%) and 24 patients (28.2%) received HF-WBI-SIB with RNI. Grade 2 acute skin toxicity was found in 1.2%. The most frequent grade 2 or more hematologic toxicity was leukopenia, which occurred in 4.8% and 11% in the 2nd and 3rd week, respectively. Mean whole body integral dose was significantly higher in patients treated with RNI compared to patients treated without RNI: 162.8 ± 32.8 vs. 120.3 ± 34.7 Gy-L (p-value < 0.001). There was no statistically significant difference in acute grade 2 or more skin and hematologic toxicities between the two groups.Conclusions: HF-WBI-SIB with or without RNI is feasible with acceptable acute skin and hematologic toxicities. RNI and whole body integral dose were not associated with these acute toxicities.

Biomolecular modifications play an important role in the development of life, and previous studies have investigated the role of DNA and proteins. In the last decade, with the development of sequencing technology, the veil of epitranscriptomics has been gradually lifted. Transcriptomics focuses on RNA modifications that affect gene expression at the transcriptional level. With further research, scientists have found that changes in RNA modification proteins are closely linked to cancer tumorigenesis, progression, metastasis, and drug resistance. Cancer stem cells (CSCs) are considered powerful drivers of tumorigenesis and key factors for therapeutic resistance. In this article, we focus on describing RNA modifications associated with CSCs and summarize the associated research progress. The aim of this review is to identify new directions for cancer diagnosis and targeted therapy.

Background: Lymph node status is an important factor in determining the prognosis of patients with early gastric cancer (EGC) and preoperative diagnosis of lymph node metastasis (LNM) has some limitations. This study explored the risk factors and independent prognostic factors of LNM in EGC patients and constructed a clinical prediction model to predict LNM.Methods: Clinicopathological data of EGC patients was collected from the public Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate logistic regression was used to identify risk factors for LNM in EGC patients. The performance of the LNM model was evaluated by C-index, calibration curve, receiver operating characteristic (ROC) curve, decision curve analysis (DCA) curve, and clinical impact curve (CIC) based on the results of multivariate regression to develop a nomogram. An independent data set was obtained from China for external validation. The Kaplan-Meier method and Cox regression model were used to identify potential prognostic factors for overall survival (OS) in EGC patients.Results: A total of 3993 EGC patients were randomly allocated to a training cohort (n=2797) and a validation cohort (n=1196). An external cohort of 106 patients from the Second Hospital of Lanzhou University was used for external validation. Univariate and multivariate logistic regression showed that age, tumor size, differentiation, and examined lymph nodes count (ELNC) were independent risk factors for LNM. Nomogram for predicting LNM in EGC patients was developed and validated. The predictive model had a good discriminatory performance with a concordance index (C-index) of 0.702 (95% CI: 0.679-0.725). The calibration plots showed that the predicted LNM probabilities were the same as the actual observations in both the internal validation cohort and external validation cohort. The AUC values for the training cohort, internal validation cohort and external validation cohort were 0.702 (95% CI: 0.679-0.725), 0.709 (95% CI: 0.674-0.744) and 0.750(95% CI: 0.607-0.892), respectively, and the DCA curves and CIC showed good clinical applicability. The Cox regression model identified age, sex, race, primary site, size, pathological type, LNM, distant metastasis, and ELNC were prognostic factors for OS in EGC patients, while a year at diagnosis, grade, marital status, radiotherapy, and chemotherapy were not independent prognostic factors.Conclusion: In this study, we identified risk factors and independent prognostic factors for the development of LNM in EGC patients, and developed a relatively accurate model to predict the development of LNM in EGC patients.

CD9 is a crucial regulator of cell adhesion in the immune system and plays important physiological roles in hematopoiesis, blood coagulation or viral and bacterial infections. It is involved in the transendothelial migration of leukocytes which might also be hijacked by cancer cells during their invasion and metastasis. CD9 is found at the cell surface and the membrane of exosomes affecting cancer progression and therapy resistance. High expression of CD9 is mostly associated with good patients outcome, with a few exceptions. Discordant findings have been reported for breast, ovarian, melanoma, pancreatic and esophageal cancer, which might be related to using different antibodies or inherent cancer heterogeneity. According to in vitro and in vivo studies, tetraspanin CD9 is not clearly associated with either tumor suppression or promotion. Further mechanistic experiments will elucidate the role of CD9 in particular cancer types and specific conditions.

Introduction: Dysbiosis characterises breast cancer through direct or indirect interference in a variety of biological pathways; therefore, specific microbial patterns and diversity may be a biomarker for the diagnosis and prognosis of breast cancer. However, there is still much to determine about the complex interplay of the gut microbiome and breast cancer.Objective: This study aims to evaluate microbial alteration in breast cancer patients compared with control subjects, to explore intestine microbial modification from a range of different breast cancer treatments, and to identify the impact of microbiome patterns on the same treatment-receiving breast cancer patients.Methods: A literature search was conducted using electronic databases such as PubMed, Embase, and the CENTRAL databases up to April 2021. The search was limited to adult women with breast cancer and the English language. The results were synthesised qualitatively and quantitatively using random-effects meta-analysis.Results: A total of 33 articles from 32 studies were included in the review, representing 19 case-control, eight cohorts, and five nonrandomised intervention researches. The gut and breast bacterial species were elevated in the cases of breast tumours, a significant increase in Methylobacterium radiotolerans (p = 0.015), in compared with healthy breast tissue. Meta-analysis of different α-diversity indexes such as Shannon index (p = 0.0005), observed species (p = 0.006), and faint’s phylogenetic diversity (p < 0.00001) revealed the low intestinal microbial diversity in patients with breast cancer. The microbiota abundance pattern was identified in different sample types, detection methods, menopausal status, nationality, obesity, sleep quality, and several interventions using qualitative analysis.Conclusions: This systematic review elucidates the complex network of the microbiome, breast cancer, and therapeutic options, with the objective of providing a link for stronger research studies and towards personalised medicine to improve their quality of life.

Editorial on the Research Topic Improving our understanding of the management and pathogenesis of rare and neglected tumors of the central and peripheral nervous system The Frontiers Research Topic titled “Improving our Understanding of the Management and Pathogenesis of Rare and Neglected Tumors of the Central and Peripheral Nervous System” includes 22 articles published from May 2022 to February 2023. This collection comprises 13 original research articles, 7 case reports, and 2 reviews, with the common aim to collect information about clinical and surgical management, new diagnostic techniques (pre-, post-, and intraoperative), innovative therapeutic therapies, as well as preclinical studies based on genetic, cellular, molecular, or omic approaches, dedicated to rare tumors of the central and peripheral nervous system in both pediatric and adult populations. Although uncommon compared to other tumors, primary Central Nervous System (CNS) and Peripheral Nervous System (PNS) cancers can cause severe morbidity and mortality across all populations. Despite the efforts and care improvement dedicated to the most prevalent brain and spine tumors (such as glioblastomas, metastases, or meningiomas), some of these diseases still lack defined management plans or specific preclinical assessment of their cellular/molecular features, thus affecting patients’ management. While CNS tumors can now be much more precisely characterized than a few years ago, the translation of this increased knowledge into more effective treatments is still seriously lagging behind, in particular considering specific populations such as children or the elderly. This is particularly true for pediatric CNS tumors. In a large series of 80 children, Zhang et al. confirmed that Diffuse Intrisic Pontine Glioma (DIPG, included in Diffuse Midline Gliomas, H3K27 altered) display a broad spectrum of clinical and imaging features; whereas surgery could play a role in addition to adjuvant therapies, H3K27 alteration was the independent prognostic influencing factor. Falco et al. analyzed the role of intraoperative fluorescent dyes in the surgical management of pleomorphic xanthoastrocytoma (PXA), a rare brain tumor most commonly affecting children and young adults. Surgical resection is the mainstay of treatment, and the extent of resection is associated with improved survival. Among the twelve patients included, comprising three pediatric patients, sodium fluorescein helped distinguish tumors from viable tissue in all cases. Their data suggest a role in improving the extent of resection during surgery of PXA. Merchant et al. presented a case of Oligodendroglioma IDH-mutant and 1p/19q-codeleted associated with a germline mutation in PMS2 like Lynch Syndrome, to evaluate the role of germline PMS2 mutations in gliomas, and highlighted the importance of genetic testing in neuro-oncology. Frederico et al. elegantly analyzed the heterogenicity among adult patients harboring MN1-altered CNS tumors. These uncommon lesions were recently added to the 2021 WHO classification under the name Astroblastoma, MN1-altered. Thought to occur most commonly in children and predominantly in females, MN1-altered CNS tumors are associated with typical (whereas not pathognomonic) histological patterns, with a distinct DNA methylation profile and recurrent fusions implicating the MN1 (meningioma 1) gene. The authors emphasize the diagnostic challenges, considering that most cases with morphological features of astroblastoma (but not all) show these molecular features, whereas not all tumors with MN1 fusions show astroblastoma morphology. From a clinical point of view, there is significant variability in reported outcomes: multiple recurrences are frequent, despite multimodality treatments. Additionally, the authors propose a standardized model for patient-reported outcomes. Pavlova et al. evaluated, in the preclinical setting, the effect of radiation therapy on patient-derived glioblastoma cells to evaluate the contribution of homologous recombination and nonhomologous end in DNA break repair after exposure to different radiation doses. Solitary fibrous tumor (SFT), previously known as hemangiopericytoma or SFT/hemangiopericytoma, is a rare intracranial malignancy thought to originate from pericyte cells lining the capillary walls. These tumors represent less than 1% of intracranial tumors and are frequently mistaken for meningiomas on imaging. Unlike most meningiomas, however, SFT has a propensity for local recurrence and extracranial metastasis after resection. Surgery usually represents the pivotal therapeutic point, but the role of adjuvant treatment is often unclear. Three papers analyzed the impact of radiation therapy in the management of SFT. Liu et al. evaluated 38 patients with SFT, confirming that patients with high WHO-grade SFT have an impaired PFS and reduced OS, which appears even more negatively affected by a subtotal resection. Postoperative radiotherapy increases the local control rate in patients with WHO grade 3 tumors. Gou et al. focused on the role of postoperative stereotactic radiosurgery or intensity-modulated radiotherapy; this second option seems to increase disease-free survival compared to radiosurgery. Finally, Allen et al. proposed for the first time the use of a mixed-modality, multi-fraction radiosurgery technique to treat recurrent SFT, to maximize radiation dose to the targets while minimizing complication risk after resection. Three papers analyzed different aspects of intracranial lymphomas, considering that intracranial lymphomas can mimic different brain tumors. Yang et al. evaluated the impact of risk factors such as age, Ann Arbor stage, and treatment in the prognosis of primary intracranial malignant lymphomas. Cheng et al. evaluated a series of primary ventricular lymphomas, an extremely rare and frequently misdiagnosed disease, with high mortality (median survival time of 15...

Objective: To explore the clinical safety and efficacy of single and multiple applications of lobaplatin-based hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with T4 gastric cancer and to evaluate the impact of HIPEC on peritoneal metastasis.Materials and methods: We retrospectively reviewed prospectively collected data from T4 gastric cancer patients who underwent radical gastric resection plus HIPEC between March 2018 and August 2020 from the National Cancer Center and Huangxing Cancer Hospital. Patients who underwent radical surgery and HIPEC were divided into two groups: the single-HIPEC group (radical resection + a single application of intraoperative HIPEC with lobaplatin 50 mg/m2 at 43.0 ± 0.5°C for 60 min), and a multi-HIPEC group (two more HIPEC applications were performed after radical surgery).Results: A total of 78 patients were enrolled in this two-center study; among them, 40 patients were in the single-HIPEC group, and 38 patients were in the multi-HIPEC group. The baseline characteristics were well balanced between the two groups. There was no significant difference in the postoperative complication rates between the two groups (P > 0.05). Mild renal dysfunction, mild liver dysfunction, low platelet levels and low white blood cell levels were recorded in both groups, without significant differences between the two groups (P > 0.05). After a mean follow-up of 36.8 months, 3 (7.5%) patients in the single-HIPEC group and 2 (5.2%) patients in the multi-HIPEC group experienced peritoneal recurrence (P > 0.05). Both groups had comparable 3-year overall survival (OS) (51.3% vs. 54.5%, P = 0.558) and 3-year disease-free survival (DFS) rates (44.1% vs. 45.7%, P = 0.975). Multivariate analysis showed that an age > 60 years and low preoperative albumin levels were independent risk factors for postoperative complications.Conclusion: Single and multiple applications of HIPEC in patients with T4 gastric cancer were safe and feasible. Both groups had similar postoperative complication rates, 3-year OS rates and 3-year DFS rates. Special attention should be given to HIPEC for patients aged > 60 years and patients with low preoperative albumin levels.

Background: Cholangiocarcinoma (CCA) is a highly heterogeneous malignant tumor, and more than 60% of patients have recurrence and metastasis after surgery. The efficacy of postoperative adjuvant therapy for CCA remains unclear. This study aimed to explore whether adjuvant therapy benefits patients with CCA and examine the independent prognostic factors for overall survival (OS) and progression-free survival (PFS).Methods: Patients with CCA undergoing surgery were retrospectively enrolled in this study from June 2016 to June 2022. The chi-square test or Fisher exact test was used to analyze the correlation between clinicopathologic characteristics. Survival curves were plotted using the Kaplan-Meier method, and the Cox regression model was used for univariate and multivariate analysis to search for independent prognostic factors.Results: Of the 215 eligible patients, 119 patients received adjuvant therapy, and the other 96 patients did not. The median follow-up was 37.5 months. The median OS of CCA patients with and without adjuvant therapy was 45 and 18 months (P < 0.001), respectively. The median PFS of CCA patients with and without adjuvant therapy was 34 and 8 months (P < 0.001), respectively. The Cox univariate and multivariate regression analysis showed that preoperative aspartate transaminase and carbohydrate antigen 19-9, microvascular invasion, lymph node metastasis, differentiation degree, and adjuvant therapy were independent prognostic factors for OS (all P values < 0.05). Preoperative carbohydrate antigen 125, microvascular invasion, lymph node metastasis, differentiation degree, and adjuvant therapy were independent prognostic factors for PFS (all P values < 0.05). The stratified analysis by TMN stage detected significant differences in the early stages (median OS [mOS]: P = 0.0128; median PFS [mPFS]: P = 0.0209) and advanced stages (mOS and mPFS: both P values < 0.001). Adjuvant therapy was also identified as a significantly favorable prognostic factor for OS and PFS in the early stages and advanced stages.Conclusion: Postoperative adjuvant therapy can improve the prognosis of patients with CCA, even in the early stages and advanced stages. All data suggest that adjuvant therapy should be incorporated into the treatment of CCA in all cases, where appropriate.

Background: About 15% of Triple-Negative-Breast-Cancer (TNBC) present silencing of the BRCA1 promoter methylation and are assumed to be Homologous Recombination Deficient (HRD). BRCA1-methylated (BRCA1-Me) TNBC could, thus, be eligible to treatment based on PARP-inhibitors or Platinum salts. However, their actual HRD status is discussed, as these tumors are suspected to develop resistance after chemotherapy exposure.Methods: We interrogated the sensitivity to olaparib vs. carboplatin of 8 TNBC Patient-Derived Xenografts (PDX) models. Four PDX corresponded to BRCA1-Me, of which 3 were previously exposed to NeoAdjuvant-Chemotherapy (NACT). The remaining PDX models corresponded to two BRCA1-mutated (BRCA1-Mut) and two BRCA1-wild type PDX that were respectively included as positive and negative controls. The HRD status of our PDX models was assessed using both genomic signatures and the functional BRCA1 and RAD51 nuclear foci formation assay. To assess HR restoration associated with olaparib resistance, we studied pairs of BRCA1 deficient cell lines and their resistant subclones.Results: The 3 BRCA1-Me PDX that had been exposed to NACT responded poorly to olaparib, likewise BRCA1-WT PDX. Contrastingly, 3 treatment-naïve BRCA1-deficient PDX (1 BRCA1-Me and 2 BRCA1-mutated) responded to olaparib. Noticeably, the three olaparib-responsive PDX scored negative for BRCA1- and RAD51-foci, whereas all non-responsive PDX models, including the 3 NACT-exposed BRCA1-Me PDX, scored positive for RAD51-foci. This suggested HRD in olaparib responsive PDX, while non-responsive models were HR proficient. These results were consistent with observations in cell lines showing a significant increase of RAD51-foci in olaparib-resistant subclones compared with sensitive parental cells, suggesting HR restoration in these models.Conclusion: Our results thus support the notion that the actual HRD status of BRCA1-Me TNBC, especially if previously exposed to chemotherapy, may be questioned and should be verified using the BRCA1- and RAD51-foci assay.

In the United States, an individual’s access to resources, insurance status, and wealth are critical social determinants that affect both the risk and outcomes of many diseases. One disease for which the correlation with socioeconomic status (SES) is less well-characterized is glioblastoma (GBM), a devastating brain malignancy. The aim of this study was to review the current literature characterizing the relationship between area-level SES and both GBM incidence and prognosis in the United States. A query of multiple databases was performed to identify the existing data on SES and GBM incidence or prognosis. Papers were filtered by relevant terms and topics. A narrative review was then constructed to summarize the current body of knowledge on this topic. We obtained a total of three papers that analyze SES and GBM incidence, which all report a positive correlation between area-level SES and GBM incidence. In addition, we found 14 papers that focus on SES and GBM prognosis, either overall survival or GBM-specific survival. Those studies that analyze data from greater than 1,530 patients report a positive correlation between area-level SES and individual prognosis, while those with smaller study populations report no significant relationship. Our report underlines the strong association between SES and GBM incidence and highlights the need for large study populations to assess SES and GBM prognosis to ideally guide interventions that improve outcomes. Further studies are needed to determine underlying socio-economic stresses on GBM risk and outcomes to identify opportunities for intervention.

Objective: Exposing tumor antigens to the immune system is the key to ensuring the efficacy of immunotherapy. SBRT is the main way to reveal the specifical antigens of tumors which can enhance the immune response. We aimed to explore the clinical efficacy and safety of Toripalimab combined with Anlotinib for uHCC after SBRT.Methods: This is a prospective, single-arm, explorative clinical study. uHCC patients with an ECOG PS score of 0–1, Child–Pugh class A or B, and BCLC stage B or C were included and treated with SBRT(8Gy*3) followed by 6-cycle combinational therapy with Toripalimab and Anlotinib. The primary endpoint was progression-free survival (PFS) and the secondary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival (OS), and incidence of treatment-related adverse events (TRAEs). Continuous variables were presented as medians and ranges. Survivals were studied with the Kaplan-Meier method. Categorical data were expressed as n (percentage).Results: Between June 2020 and October 2022, a total of 20 patients with intermediate-advanced uHCC were enrolled. All cases had multiple intrahepatic metastases, or macrovascular invasion, or both, among whom 5 cases with lymph node or distant metastases. Until September 2022, the median follow-up time was 7.2 months (range, 1.1-27.7 months). Median survival time could not be assessed at the moment, based on iRecist, median PFS was 7.4 months (range, 1.1-27.7 months), ORR 15.0%, and DCR 50.0%. 14 patients experienced treatment-related adverse events with an incidence of 70%. The overall survival rates at 18 months and 24 months were 61.1% and 50.9%, respectively. And the progression-free survival rates were 39.3% and 19.7%.Conclusion: Exposure of specific antigens of HCC via SBRT may improve the efficacy of combinational therapy with Toripalimab and Anlotinib for uHCC with manageable adverse effects, which deserves further exploration.Clinical trial registration: www.clinicaltrials.gov, identifier ChiCTR2000032533.

Ovarian, endometrial, and cervical cancer are common gynecologic malignancies, and their incidence is increasing year after year, with a younger patient population at risk. An exosome is a tiny “teacup-like” blister that can be secreted by most cells, is highly concentrated and easily enriched in body fluids, and contains a large number of lncRNAs carrying some biological and genetic information that can be stable for a long time and is not affected by ribonuclease catalytic activity. As a cell communication tool, exosome lncRNA has the advantages of high efficiency and high targeting. Changes in serum exosome lncRNA expression in cancer patients can accurately reflect the malignant biological behavior of cancer cells. Exosome lncRNA has been shown in studies to have broad application prospects in cancer diagnosis, monitoring cancer recurrence or progression, cancer treatment, and prognosis. The purpose of this paper is to provide a reference for clinical research on the pathogenesis, diagnosis, and treatment of gynecologic malignant tumors by reviewing the role of exosome lncRNA in gynecologic cancers and related molecular mechanisms.

Osteosarcoma (OS) is a primary malignant tumor of bone characterized by the formation of bone tissue or immature bone by tumor cells. Because of its multi-drug resistance, even with the improvement of chemotherapy and the use of targeted drugs, the survival rate of osteosarcoma (OS) is still less than 60%, and it is easy to metastasize, which is a difficulty for many clinicians and researchers. In recent years, with the continuous research on exosomes, it has been found that exosomes play a role in the diagnosis, treatment and chemotherapy resistance of osteosarcoma due to their unique properties. Exosomes can reduce the intracellular accumulation of chemotherapeutic drugs by mediating drug efflux, thus inducing chemotherapeutic resistance in OS cells. Exosomal goods (including miRNA and functional proteins) carried by exosomes also show great potential in affecting the drug resistance of OS. In addition, miRNA carried by exosomes and exosomes exist widely in tumor cells and can reflect the characteristics of parent cells, so it can also be used as a biomarker of OS. At the same time, the development of nanomedicine has given a new hope for the treatment of OS. Exosomes are regarded as good natural nano-carriers by researchers because of their excellent targeted transport capacity and low toxicity, which will play an important role in the field of OS therapy in the future. This paper reviews the internal relationship between exosomes and OS chemotherapy resistance, discusses the broad prospects of exosomes in the field of diagnosis and treatment of OS, and puts forward some suggestions for the study of the mechanism of OS chemotherapy resistance.

Introduction: The leukemic cells of patients with chronic lymphocytic leukemia (CLL) are often unique, expressing remarkably similar IGHV-IGHD-IGHJ gene rearrangements, “stereotyped BCRs”. The B-cell receptors (BCRs) on CLL cells are also distinctive in often deriving from autoreactive B lymphocytes, leading to the assumption of a defect in immune tolerance.Results: Using bulk and single-cell immunoglobulin heavy and light chain variable domain sequencing, we enumerated CLL stereotype-like IGHV-IGHD-IGHJ sequences (CLL-SLS) in B cells from cord blood (CB) and adult peripheral blood (PBMC) and bone marrow (BM of healthy donors. CLL-SLS were found at similar frequencies among CB, BM, and PBMC, suggesting that age does not influence CLL-SLS levels. Moreover, the frequencies of CLL-SLS did not differ among B lymphocytes in the BM at early stages of development, and only re-circulating marginal zone B cells contained significantly higher CLL-SLS frequencies than other mature B-cell subpopulations. Although we identified CLL-SLS corresponding to most of the CLL major stereotyped subsets, CLL-SLS frequencies did not correlate with those found in patients. Interestingly, in CB samples, half of the CLL-SLS identified were attributed to two IGHV-mutated subsets. We also found satellite CLL-SLS among the same normal samples, and they were also enriched in naïve B cells but unexpectedly, these were ~10-fold higher than standard CLL-SLS. In general, IGHV-mutated CLL-SLS subsets were enriched among antigen-experienced B-cell subpopulations, and IGHV-unmutated CLL-SLS were found mostly in antigen-inexperienced B cells. Nevertheless, CLL-SLS with an IGHV-mutation status matching that of CLL clones varied among the normal B-cell subpopulations, suggesting that specific CLL-SLS could originate from distinct subpopulations of normal B cells. Lastly, using single-cell DNA sequencing, we identified paired IGH and IGL rearrangements in normal B lymphocytes resembling those of stereotyped BCRs in CLL, although some differed from those in patients based on IG isotype or somatic mutation.Discussion: CLL-SLS are present in normal B-lymphocyte populations at all stages of development. Thus, despite their autoreactive profile they are not deleted by central tolerance mechanisms, possibly because the level of autoreactivity is not registered as dangerous by deletion mechanisms or because editing of L-chain variable genes occurred which our experimental approach could not identify.

Introduction: Anaplastic lymphoma kinase (ALK) fusion mutation is more common in younger and never-smoking lung cancer patients. The association of smoking and ALK-tyrosine kinase inhibitors (TKIs) on overall survival (OS) of treatment-naïve ALK-positive advanced lung adenocarcinoma remains unclear in real-world.Methods: This retrospective study evaluated all 33170 lung adenocarcinoma patients registered in the National Taiwan Cancer Registry from 2017 to 2019, of whom 9575 advanced stage patients had ALK mutation data.Results: Among the 9575 patients, 650 (6.8%) patients had ALK mutation with the median follow-up survival time 30.97 months (median age, 62 years; 125 [19.2%] were aged ≥75 years; 357 (54.9%) females; 179 (27.5) smokers, 461 (70.9%) never-smokers, 10 (1.5%) with unknown smoking status; and 544 (83.7%) with first-line ALK-TKI treatment). Overall, of 535 patients with known smoking status who received first-line ALK-TKI treatment, never-smokers and smokers had a median OS of 40.7 months (95% confidence interval (CI), 33.1-47.2 months) and 23.5 months (95% CI, 11.5-35.5 months) (P=0.015), respectively. Among never-smokers, those who received first-line ALK-TKI treatment had a median OS of 40.7 months (95% CI, 22.7-57.8 months), while those ALK-TKI not as first-line treatment had a median OS of 31.7 months (95% CI, 15.2-42.8 months) (P=0.23). In smokers, the median OS for these patients was 23.5 months (95% CI, 11.5-35.5 months) and 15.6 months (95% CI, 10.2-21.1 months) (P=0.026), respectively.Conclusions and relevance: For patients with treatment-naïve advanced lung adenocarcinoma, the ALK test should be performed irrespective of smoking status and age. Smokers had shorter median OS than never-smokers among treatment-naïve-ALK-positive patients with first-line ALK-TKI treatment. Furthermore, smokers not receiving first-line ALK-TKI treatment had inferior OS. Further investigations for the first-line treatment of ALK-positive smoking advanced lung adenocarcinoma patients are needed.

Ferroptosis is a new form of regulatory cell death that is closely related to the balance of redox reactions and the occurrence and development of cancer. There is increasing evidence that inducing ferroptosis in cells has great potential in the treatment of cancer. Especially when combined with traditional therapy, it can improve the sensitivity of cancer cells to traditional therapy and overcome the drug resistance of cancer cells. This paper reviews the signaling pathways regulating ferroptosis and the great potential of ferroptosis and radiotherapy (RT) in cancer treatment and emphasizes the unique therapeutic effects of ferroptosis combined with RT on cancer cells, such as synergy, sensitization and reversal of drug resistance, providing a new direction for cancer treatment. Finally, the challenges and research directions for this joint strategy are discussed.

Papillary renal neoplasm with reverse polarity (PRNRP) is a rare renal tumour and was newly named in 2019. This study reported a case of a 30-year-old female patient with a left renal tumour without any clinical symptoms and whose CT scan of her left kidney showed a mass of 2.6 cm×2.3 cm, which was considered to be renal clear cell carcinoma. Laparoscopic partial nephrectomy was performed, and histopathology and immunohistochemistry confirmed papillary renal neoplasm with reverse polarity, which had unique clinicopathological features, immunophenotype, KRAS gene mutation and relatively indolent biological behaviour. As newly diagnosed cases, rigorous and regular follow-up is necessary. In addition, a literature review was performed from 1978 to 2022, and 97 cases of papillary renal neoplasms with reverse polarity were identified and analysed.

Introduction: Preoperative diagnosis of benign and malignant thyroid nodules is crucial for appropriate clinical treatment and individual patient management. In this study, a double-layer spectral detector computed tomography (DLCT)-based nomogram for the preoperative classification of benign and malignant thyroid nodules was developed and tested. Methods: A total of 405 patients with pathological findings of thyroid nodules who underwent DLCT preoperatively were retrospectively recruited. They were randomized into a training cohort (n=283) and a test cohort (n=122). Information on clinical features, qualitative imaging features and quantitative DLCT parameters was collected. Univariate and multifactorial logistic regression analyses were used to screen independent predictors of benign and malignant nodules. A nomogram model based on the independent predictors was developed to make individualized predictions of benign and malignant thyroid nodules. Model performance was evaluated by calculating the area under the receiver operating characteristic curve (AUC), calibration curve and decision curve analysis(DCA). Results: Standardized iodine concentration in the arterial phase, the slope of the spectral hounsfield unit(HU) curves in the arterial phase, and cystic degeneration were identified as independent predictors of benign and malignant thyroid nodules. After combining these three metrics, the proposed nomogram was diagnostically effective, with AUC values of 0.880 for the training cohort and 0.884 for the test cohort. The nomogram showed a better fit (all p > 0.05 by Hosmer−Lemeshow test) and provided a greater net benefit than the simple standard strategy within a large range of threshold probabilities in both cohorts. Discussion: The DLCT-based nomogram has great potential for the preoperative prediction of benign and malignant thyroid nodules. This nomogram can be used as a simple, noninvasive, and effective tool for the individualized risk assessment of benign and malignant thyroid nodules, helping clinicians make appropriate treatment decisions.

Introduction: The Like-Smith (LSM) family plays a critical role in the progression of several cancers. However, the function of LSMs in chemoresistance of gastric cancer (GC) is still elusive.Methods: The Cancer Genome Atlas (TCGA) database, Gene Expression Omnibus (GEO) database and Tumor Immune Estimation Resource Analysis (TIMER) were utilized to analyze the expression, prognostic value and immune infiltration of LSMs in GC patients. Moreover, qPCR and immunohistochemistry (IHC) experiment were conducted with clinical samples.Results: The expression of LSMs was upregulated in GC tissues and most of LSMs were negatively correlated with overall survival of GC patients with 5-fluorouracil (5-FU) treatment. We further revealed that LSM5, 7 and 8 were hub genes of GEO (GSE14210). Besides, the qPCR results demonstrated that a higher level of LSM5 and LSM8 was associated with 5-FU chemoresistance in GC. Moreover, both TIMER and IHC revealed that a lower expression of LSM5 and LSM8 was correlated with high infiltration of T cells, regulatory T cells, B cells, macrophages, and neutrophils.Discussion: Our study systematically investigated the expression pattern and biological features of LSM family members in GC, and identified LSM5 and LSM8 as potential biomarkers in GC with 5-FU chemotherapy.

Aim: This study aims to assess the clinical influence of enlarged cardiophrenic lymph nodes (CPLN) on staging computed tomography (CT) among patients with advanced ovarian cancer.Methods: This retrospective cohort study included 320 patients with advanced epithelial ovarian cancer who underwent staging CT from May 2008 to January 2019. The CPLN diameter was the average of two radiologists’ measurements. Enlarged CPLN was defined as a short-axis diameter of ≥5 mm. Clinical and imaging findings, management decisions, and progression-free survival(PFS) were compared between patients with and without enlarged CPLN.Results: Enlarged CPLN was found in 129 (40.3%) patients, which was significantly associated with more pelvic peritoneal carcinomatosis (odds ratio [OR]: 6.61 with 95% confidence interval [CI]: 1.51–28.99), and involved the greater omentum (OR: 6.41, 95% CI: 3.05–13.46), spleen capsule nodules (OR: 2.83, 95% CI: 1.58–5.06), and liver capsule nodules (OR: 2.55, 95% CI: 1.57–4.17). The optimal cytoreduction rates did not differ between patients with and without enlarged CPLN (p = 0.656). The presence of enlarged CPLN had a significant negative influence on PFS (median PFS, 23.5 vs. 80.6 months, respectively, CPLN ≥5 mm versus <5 mm; p = 0.023) in patients with no RD after primary debulking surgery, but no adverse effect on PFS among patients with RD (median PFS, 28.0 vs. 24.4 months, respectively, CPLN ≥5 mm versus <5 mm; p = 0.359). However, enlarged CPLN on staging CT did not affect PFS in patients treated with neoadjuvant chemotherapy, with (median PFS, 22.4 vs. 23.6 months, respectively, CPLN ≥5 mm versus <5 mm; p = 0.360) or without RD (median PFS, 17.7 vs. 23.3 months, respectively, CPLN ≥5 mm versus <5 mm; p = 0.400). The enlarged CPLN showed a decreased trend in 81.6% (n = 80) of the patients with enlarged CPLN. No significant difference was found in PFS (p = 0.562) between patients with decreased and increased in the size of CPLN.Conclusions: Enlarged CPLN on staging CT is associated with more abdominal disease but is not reliable in predicting complete resection. Enlarged CPLN awareness is necessary for patients with a primary chance of complete resection of abdominal disease.

Background: Machine learning is now well-developed in non-small cell lung cancer (NSCLC) radiotherapy. But the research trend and hotspots are still unclear. To investigate the progress in machine learning in radiotherapy NSCLC, we performed a bibliometric analysis of associated research and discuss the current research hotspots and potential hot areas in the future.Methods: The involved researches were obtained from the Web of Science Core Collection database (WoSCC). We used R-studio software, the Bibliometrix package and VOSviewer (Version 1.6.18) software to perform bibliometric analysis.Results: We found 197 publications about machine learning in radiotherapy for NSCLC in the WoSCC, and the journal Medical Physics contributed the most articles. The University of Texas MD Anderson Cancer Center was the most frequent publishing institution, and the United States contributed most of the publications. In our bibliometric analysis, “radiomics” was the most frequent keyword, and we found that machine learning is mainly applied to analyze medical images in the radiotherapy of NSCLC.Results: The research we identified about machine learning in NSCLC radiotherapy was mainly related to the radiotherapy planning of NSCLC and the prediction of treatment effects and adverse events in NSCLC patients who were under radiotherapy. Our research has added new insights into machine learning in NSCLC radiotherapy and could help researchers better identify hot research areas in the future.

Objectives: To investigate the characteristics, diagnosis, survival and prognosis of second primary breast carcinoma (SPBC).Materials and methods: Records of 123 patients with SPBC in Tianjin Medical University Cancer Institute & Hospital between December 2002 and December 2020 were retrospectively reviewed. Clinical characteristics, imaging features and survival were analyzed and comparisons between SPBC and breast metastases (BM) were made.Results: Of 67156 newly diagnosed breast cancer patients, 123 patients (0.18%) suffered previous extramammary primary malignancies. Of the 123 patients with SPBC, approximately 98.37%(121/123)were female. The median age was 55 years old (27-87). The average diameter of breast mass was 2.7 cm (0.5-10.7). Approximately 77.24% (95/123) of the patients presented with symptoms. The most common types of extramammary primary malignancies were thyroid, gynecological cancers, lung, and colorectal. Patients with the first primary malignant tumor of lung cancer were more likely to develop synchronous SPBC, and those with the first primary malignant tumor of ovarian cancer were more likely to develop metachronous SPBC. When comparing with BM, patients with SPBC were more often older (≥45 years old), at earlier stages (I/II), more microcalcification and less multiple breast masses in imaging. More than half (55.88%) of patients in the metachronous group developed primary breast cancer within 5 years after diagnosis of extramammary primary cancer. The median overall survival time was 71 months. Within 90 months, the prognosis of patients with synchronous SPBC was worse than that of patients with metachronous SPBC (p=0.014). Patients with BM had the worst outcome compared with patients with synchronous SPBC and metachronous SPBC (p<0.001).ER/PR-negative status, an interval of less than 6 months between the onset of two tumors, a late stage of first primary malignancy, and an age of diagnosis of first primary malignancy greater than 60 years predicted a worse prognosis for patients with SPBC.Conclusion: The possibility of SPBC should be considered during the follow-up of patients with primary extramammary malignancy, especially within 5 years of the onset of the first tumor. The stage of first primary malignancy and the age at diagnosis of first primary malignancy have an impact on the prognosis of patients with SPBC.

The adverse effects of lactic acidosis in the cancer microenvironment have been increasingly recognized. Dichloroacetate (DCA) is an orally bioavailable, blood brain barrier penetrable drug that has been extensively studied in the treatment of mitochondrial neurologic conditions to reduce lactate production. Due to its effect reversing aerobic glycolysis (i.e., Warburg-effect) and thus lactic acidosis, DCA became a drug of interest in cancer as well. Magnetic resonance spectroscopy (MRS) is a well-established, non-invasive technique that allows detection of prominent metabolic changes, such as shifts in lactate or glutamate levels. Thus, MRS is a potential radiographic biomarker to allow spatial and temporal mapping of DCA treatment. In this systematic literature review, we gathered the available evidence on the use of various MRS techniques to track metabolic changes after DCA administration in neurologic and oncologic disorders. We included in vitro, animal, and human studies. Evidence confirms that DCA has substantial effects on lactate and glutamate levels in neurologic and oncologic disease, which are detectable by both experimental and routine clinical MRS approaches. Data from mitochondrial diseases show slower lactate changes in the central nervous system (CNS) that correlate better with clinical function compared to blood. This difference is most striking in focal impairments of lactate metabolism suggesting that MRS might provide data not captured by solely monitoring blood. In summary, our findings corroborate the feasibility of MRS as a pharmacokinetic/pharmacodynamic biomarker of DCA delivery in the CNS, that is ready to be integrated into currently ongoing and future human clinical trials using DCA.

Objective: Gastric cancer has a poor prognosis and high mortality. Cuproptosis, a novel programmed cell death, is rarely studied in gastric cancer. Studying the mechanism of cuproptosis in gastric cancer is conducive to the development of new drugs, improving the prognosis of patients and reducing the burden of disease.Methods: The TCGA database was used to obtain transcriptome data from gastric cancer tissues and adjacent tissues. GSE66229 was used for external verification. Overlapping genes were obtained by crossing the genes obtained by differential analysis with those related to copper death. Eight characteristic genes were obtained by three dimensionality reduction methods: lasso, SVM, and random forest. ROC and nomogram were used to estimate the diagnostic efficacy of characteristic genes. The CIBERSORT method was used to assess immune infiltration. ConsensusClusterPlus was used for subtype classification. Discovery Studio software conducts molecular docking between drugs and target proteins.Results: We have established the early diagnosis model of eight characteristic genes (ENTPD3, PDZD4, CNN1, GTPBP4, FPGS, UTP25, CENPW, and FAM111A) for gastric cancer. The results are validated by internal and external data, and the predictive power is good. The subtype classification and immune type analysis of gastric cancer samples were performed based on the consensus clustering method. We identified C2 as an immune subtype and C1 as a non-immune subtype. Small molecule drug targeting based on genes associated with cuproptosis predicts potential therapeutics for gastric cancer. Molecular docking revealed multiple forces between Dasatinib and CNN1.Conclusion: The candidate drug Dasatinib may be effective in treating gastric cancer by affecting the expression of the cuproptosis signature gene.

Aim: A prospective dose escalation trial was developed to evaluate the maximum tolerated dose of stereotactic body radiotherapy (SABRT) to primary breast cancer in stage IV disease. The aim of the present report was to describe safety and outcome of the first dose level cohort of patients.Material and methods: Patients with histologically confirmed diagnosis of invasive breast carcinoma (biological immuno-histochemical profile: luminal and/or HER2 positive) and distant metastatic disease not progressing after 6 months of systemic therapy with a tumor CT or 5FDG-PET detectable were deemed eligible. The starting dose was 40 Gy in 5 fractions (level 1) because this dose proved to be safe in previous dose-escalation trial on adjuvant stereotactic body radiotherapy. The maximum dose level was chosen as 45 Gy in 5 fractions. Dose limiting toxicity was any grade 3 or worse toxicity according to CTCAE v.4. Time-to-event Keyboard (TITE-Keyboard) design (Lin and Yuan, Biostatistics 2019) was used to find the maximum tolerated dose (MTD). MTD was the dose of radiotherapy associated with a ≤ 20% rate pre-specified treatment-related dose-limiting toxicity (DLT).Results: To date 10 patients have been treated at the starting dose level. Median age was 80 years (range 50-89). 7 patients had a luminal disease, while 3 patients had an HER2 positive disease. No patient suspended ongoing systemic treatment. No protocol defined DLTs were observed. Grade 2 skin toxicity occurred in 4 patients with diseases located close to or involving the skin. Median follow-up was 13 months and all 10 patients were evaluable for response: 5 achieved a complete response, 3 achieved a partial response and 2 showed a stable disease, all with a clinical benefit (resolution of skin retraction, bleeding and pain). The mean reduction in the sum of the largest diameters of target lesions was of 61.4% (DS=17.0%).Conclusions: SABR to primary breast cancer seems feasible and is associated with symptoms reduction. Continued accrual to this study is needed to confirm the safety and assess the MTD.Clinical trial registration: ClinicalTrials.gov, identifier NCT05229575.

Editorial on the Research Topic Women in radiation oncology: 2021 In this special edition of Frontiers in Oncology, we would like to start by thanking all the contributors and congratulating them for their fine efforts. This edition highlights the importance of research mentorship, especially for women in the subspecialty of radiation oncology. During the recent pandemic, there has been an increased emphasis on innovative ways to improve access to cancer care for women. In this edition, we will highlight papers that aim to shed light on novel advances, including the use of accelerated radiation, stereotactic body radiation therapy (SBRT), and artificial intelligence. Highly aggressive triple-negative breast cancer (TNBC) is typically treated with neoadjuvant chemotherapy and immunotherapy (1–3). The specific radiobiological characteristics of TNBC tumor cells and their response to different RT fractionation regimens had not been fully elucidated. To address this, Grosche et al. studied the effects of normo-fractionated RT (NormRT) of 50Gy in 2Gy per fraction compared to hypo-fractionated RT (HypoRT) of 40Gy in 2.67Gy per fraction in a normal epithelial breast cancer cell line (MCF10A) and compared these results to those of 2 TNBC BRCA mutant cell lines (HCC1395 and HCC1937). Altogether, these preclinical data support previous studies on the equal effectiveness at the cellular level of NormoRT and HypoRT as tested by this group in vitro. The additional use of preclinical models, including patient-derived xenografts, to assess the impact of metabolic and spatial heterogeneity (4) in short- and long-term responses to treatment should also be examined. The use of accelerated partial breast irradiation (APBI) for younger patients with high-risk features, including the TNBC subtype, continues to be an area of controversy. Goulding et al. reported on a retrospective analysis of 269 patients with high-risk characteristics, including TNBC, ER, tumor size < 3 cm, and age 40-50, who were receiving 38.5 Gy BID in 10 fx. High-risk features, including TNBC and ER histology, were significantly correlated with an increased risk of axillary recurrence. These data highlight the need for further investigation into the use of APBI for younger patients with high-risk features (5). The benefit of SBRT for breast cancer patients with oligometastatic disease remains an area of continued investigation (6, 7). Lemoine et al. performed a retrospective analysis of the use of SBRT in oligometastatic breast cancer treated with SBRT. In this study, 44 patients were included who had between two and five lesions. The patients had metastatic disease in the bone (44.4%), liver (40.7%), and lung (11.1%). Overall, the results showed high local control, low toxicities, and, in combination with systemic treatment, a progression-free survival (PFS) of greater than 80%. Vazquez et al. conducted a retrospective analysis of 708 patients who received palliative radiation therapy (RT) for metastatic disease from primary lung (31%), breast (14.8%), and gastrointestinal (14.8%) cancer. Predominantly, palliative RT was delivered to bone metastases (56%), and a single-fraction treatment was used on 34.4% (243) of the patients. The results identified that the 30-day mortality (30-DM) rate was 14.5% (124/708 patients). Importantly, the predictive factor for the 30-DM rate was performance status (ECOG) 2-3 (p= 0.0001). Increased use of single-fraction RT should be taken into consideration when offering palliative radiotherapy compared to the best supportive care. The main objective of treatment—symptom relief—should be discussed with and emphasized to our patients. Artificial intelligence (AI) is being incorporated into radiation oncology to predict outcomes, improve patient selection, optimize treatment planning, and generate auto-contouring or auto-segmentation tools. Artificial intelligence or machine learning may ultimately be a useful tool for physicians to improve patient selection and treatment. Volpe et al. performed a systematic review of electronic databases that used machine learning (ML) or radiomics specifically in head and neck radiotherapy. They identified 48 studies, including 21 on auto-segmentation, 12 on oncologic outcome prediction, 10 on toxicity prediction, and 4 on treatment planning. Quantitative image features were used in 9/48 studies (19%), and computed tomography was the most used imaging modality in 40% of cases. The clinical applications of AI in radiation oncology continue to increase. The use of CT/MR imaging, auto-segmentation and auto-contouring tools, and virtual reality tools are essential for improving outcomes in radiation oncology. We hope that our readers enjoy this special edition with its emphasis on women scientists in the field of radiation oncology and that they are inspired to work together and support the mentorship of young investigators in this field. Embracing novel advances and tools is essential for improving outcomes in radiation oncology. Training our future oncologists is a necessary factor in the continued value and importance of radiation oncology in improving cancer care outcomes for women. We have a strong group of talented investigators, and the future of our field remains bright. Writing and editing the editorial CM, CT, review editorial. All authors contributed to the article and approved the submitted version. Thank you to Dr. Stoyanova and Mihai for their contributions. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is...

An Erratum on Is liquid biopsy the future commutator of decision-making in liver transplantation for hepatocellular carcinoma? By Gonvers S, Tabrizian P, Melloul E, Dormond O, Schwartz M, Demartines N and Labgaa I (2022) Front. Oncol. 12:940473. doi: 10.3389/fonc.2022.940473 An omission to the funding section of the original article was made in error. The following sentence has been added: “Open access funding was provided by the University of Lausanne”. The original version of this article has been updated. Keywords: CTC (circulation tumor cells), ctDNA (circulating tumor DNA), liver cancer, transplant, biomarkers Citation: Frontiers Production Office (2023) Erratum: Is liquid biopsy the future commutator of decision-making in liver transplantation for hepatocellular carcinoma? Front. Oncol. 13:1180615. doi: 10.3389/fonc.2023.1180615 Received: 06 March 2023; Accepted: 06 March 2023; Published: 17 March 2023. Approved by: Copyright © 2023 Frontiers Production Office. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. *Correspondence: Frontiers Production Office, [email protected]

Editorial on the Research Topic Host-microbiota and cancer Cancer is the 2^nd leading cause of death in the United States, making up an average of 21% of deaths in both genders (1). The COVID-19 pandemic impacted the diagnosis and treatment of cancer, starting from its peak in mid-2020 and still recovering (2). With continued mortality and incidence due to this disease, research has migrated to other areas of interest for mechanisms to aid cancer management, such as exosomes, nucleic acids, and, more innovatively, the gut microbiota. The human microbiome is a complex community composed of various microorganisms, including bacteria, viruses, fungi, and protozoans. It contains approximately 100 trillion microorganisms and can be found at different body points, such as the skin and respiratory system. Still, the majority commonly reside in the gastrointestinal region (3). The connection between microbiome and health began to be established with the microbiome having evolving links in cardiovascular, inflammatory bowel disease, and cancer (4–6). Within the scope of cancer, it is now well known that a high involvement of microbiota can indirectly or directly affect the occurrence, treatment outcome, and drug resistance. For example, Helicobacter pylori are cancer-related pathogen that can increase the incidence of gastric cancer (7). This microorganism and others will generally be responsible for approximately 20% of cancer cases (8). Additionally, the microbiota in the body has been found to have interactions in the tumor microenvironment and has ways to promote or regulate carcinogenesis and cancer therapeutic response. This can occur through signaling pathways, inducing DNA damage, and immune system regulation (9). The ability of the human microbiota to play a functional role in carcinogenesis identifies it as a potential and worthy subject for further research to understand the regulatory mechanisms for pathogen-related cancers. Furthermore, research is essential and beneficial as it can aid in identifying novel therapeutics for cancer management. Studies have shown that the tumor microbiota has a different composition than normal, and the type of composition can affect different points of development and progression. The microbiome can help regulate cancer at various points and is commonly due to the significant difference in the microbiota composition. Therefore, understanding how the microbiome differs between healthy patients and those with cancer and how pathogenic infection can alter this microbiome is highly important to establish a baseline between the disease and begin identifying potential targets and mechanisms. In a study looking at glioma development, the authors were hoping to determine how glioma could alter the microbiome and, in turn, how the microbiome affected the outcome of glioma tumors (Fan et al.). Using mouse models to establish glioma models, the study was able to report a difference in the microbiome from before tumor development and the one after a tumor was established, showing that glioma tumors influence the composition of the microbiota. On the other hand, when a dysbiosis microbiome was induced through antibiotic treatment, it showed that these altered microbial environments had a worse prognosis in glioma growth, indicating that the microbiome component can interplay with tumor progression. Additionally, to further cover the study points, after identifying the differences between microorganism composition, they acknowledged specific targets for the microbiome, such as CD8 and Fox3, that can affect tumor growth. A dysbiosis microbiome has not only been found to regulate specific components in glioma tumors specifically but can also play a role in gastric cancer. This topic was discussed in a review covering the role of plasmacytoid dendritic cells (pDC) in gastric cancer (Yang et al.). In gastric cancer, there has been a noticeable alteration in the immune components, such as BDCA2+ pDCs and Foxp3+ Tregs, significantly increasing in tumor vs. normal. As the microbiome also changes in the presence of cancer, there was research to establish if this alteration could be responsible for the immune system changes seen. It was noted that the alterations in bacteria, such as Stenotrophomonas, Selenomonas, Comamonas, and Gaiella, could regulate the abundance of BDCA2+ pDCs and Foxp3+ Tregs. In addition to regulating pCD density, the microbiome was also found to modulate pCD cells themselves, specifically increasing IL-10 secretion to alter immunity. This shows that the microbiome can promote cancer progression through immune system regulation. However, the mechanism behind this alteration remains unclear, with certain studies showing possible routes through cytolytic CD8+T cells. Since the microbiome can regulate tumor growth, it is also essential to study the microbiome to understand its relationship with therapeutics and target the microbiome to help increase efficiency. The microbiome is a well-regarded environmental influencer meaning it can significantly affect chemical/immunotherapy efficiency and other aspects of treatments. Studying the microbiome in relation to therapies is especially important because it can identify essential bacteria or develop ideas to improve treatments, advance cancer management, and diminish treatment side effects. A current example is a study looking into ICI treatments, more specifically, the monoclonal antibody therapy targeting PDL1/PD1, and establishing a link between the gastrointestinal irAE caused by the treatment and the gut microbiota to better manage irAE. The authors of this study included patients who developed irAE from ICI therapies and patients diagnosed with UC. They were first able to show pathway similarities in ulcerative colitis and irAE, indicating a degree of resemblance in relation to function with the most vital genes that correlated between the two...

Ediotrial on the Research Topic Incorporation of reporting and data systems into cancer radiology The potential benefits of Reporting and Data Systems (RADS) are well known: improve the communication between the radiologists and physicians; reduce the omission of relevant information in reports; reduce the variability and errors in image interpretation; facilitate the monitoring of results and provide a tool to ensure quality and research. Furthermore, the slightest error in the interpretation of the legend describing the results of an imaging study can modify both the medical decision to start or not a treatment, and to do it with a more or less invasive technique. In this sense, for example, the American College of Radiology (ACR) started the development of the Breast Imaging Reporting and Data System (BI-RADS) in 1993. In recent years, several systems have been developed to diagnose other malignancies based on BI-RADS. However, its utility has yet to be demonstrated which is why scoring systems are continually being revised to apply them to daily clinical practice. The RADS systems developed so far are specially designed for breast, colorectal, gynecological, liver, lung, prostate and thyroid cancers. These aspects are clearly reflected in the research papers accepted in the “Incorporation of Reporting and Data Systems into Cancer Radiology” Research Topic. These manuscripts demonstrate how RADS benefit cancer patients, and how improvements to these systems can further benefit patients and optimize disease outcomes. For instance, in Wang et al., the authors investigated the value of contrast-enhanced ultrasound in the differential diagnosis and risk stratification of ACR TI-RADS category 4 and 5 thyroid nodules with non-hypovascular, establishing a risk score with ability to improve both aspects. In Sun et al., it was evaluated the value of multiparametric magnetic resonance imaging (MIR) including synthetic MRI, diffusion-weighted imaging, dynamic contrast enhanced MRI, and clinical features in breast imaging–reporting and data system (BI-RADS) 4 lesions, and develop an efficient method to help patients avoid unnecessary biopsy. In Zhou et al., the authors established a predictive model incorporating clinical features and contrast enhanced ultrasound liver imaging- reporting and data system (CEUS LI-RADS) to improve the prediction of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) patients. In Singh et al., to minimize inter-radiologist variability, the diagnostic performance of an in-house developed semi-automated model using machine learning methods for prostate imaging-reporting and data system version 2.1 (PI-RADS v2.1) scoring was evaluated in prostate cancer patients. The authors in Meng et al., assessed the value of using quantitative parameters from synthetic magnetic resonance imaging (SyMRI) and the Kaiser score (KS) to differentiate benign and malignant breast lesions in patients, identifying that the incorporation of T₁ values improves the sensitivity and specificity of the KS protocol alone. In Yang et al., a retrospective study was performed to create a predictive machine learning model based on liver imaging and reporting and data system (LI-RADS) features to identify microvascular invasion in hepatocellular carcinoma (HCC) patients, concluding that LI-RADS may help optimize the management of these patients. Finally, in Wu et al., the authors conducted a retrospective Chinese population-based study of patients screened for lung cancer by computed tomography to assess the correlation between the probability of lung cancer and the number of lung nodules, concluding that this probability does not change with the number but does change with the size of the nodules. All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. Keywords: reporting and data system, cancer imaging, magnetic resonance imaging, ultrasound, computed tomography Citation: López-Larrubia P and Santone A (2023) Editorial: Incorporation of reporting and data systems into cancer radiology. Front. Oncol. 13:1171171. doi: 10.3389/fonc.2023.1171171 Received: 21 February 2023; Accepted: 08 March 2023; Published: 17 March 2023. Edited and Reviewed by: Copyright © 2023 López-Larrubia and Santone. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. *Correspondence: Pilar López-Larrubia, [email protected]; Antonella Santone, [email protected] Incorporation of Reporting and Data Systems into Cancer Radiology

Background: Early tumor recurrence is one of the most significant poor prognostic factors for patients with HCC after R0 resection. The aim of this study is to identify risk factors of early recurrence, in addition, to develop a nomogram model predicting early recurrence of HCC patients.Methods: A total of 481 HCC patients after R0 resection were enrolled and divided into a training cohort (n = 337) and a validation cohort (n = 144). Risk factors for early recurrence were determined based on Cox regression analysis in the training cohort. A nomogram incorporating independent risk predictors was established and validated.Results: Early recurrence occurred in 37.8% of the 481 patients who underwent curative liver resection of HCC. AFP ≥ 400 ng/mL (HR: 1.662; P = 0.008), VEGF-A among 127.8 to 240.3 pg/mL (HR: 1.781, P = 0.012), VEGF-A > 240.3 pg/mL (HR: 2.552, P < 0.001), M1 subgroup of MVI (HR: 2.221, P = 0.002), M2 subgroup of MVI (HR: 3.120, P < 0.001), intratumor necrosis (HR: 1.666, P = 0.011), surgical margin among 5.0 to 10.0 mm (HR: 1.601, P = 0.043) and surgical margin < 5.0 mm (HR: 1.790, P = 0.012) were found to be independent risk factors for recurrence-free survival in the training cohort and were used for constructing the nomogram. The nomogram indicated good predictive performance with an AUC of 0.781 (95% CI: 0.729-0.832) and 0.808 (95% CI: 0.731-0.886) in the training and validation cohorts, respectively.Conclusions: Elevated serum concentrations of AFP and VEGF-A, microvascular invasion, intratumor necrosis, surgical margin were independent risk factors of early intrahepatic recurrence. A reliable nomogram model which incorporated blood biomarkers and pathological variables was established and validated. The nomogram achieved desirable effectiveness in predicting early recurrence in HCC patients.

Background: Cuproptosis is a newly discovered form of cell death induced by targeting lipoacylated proteins involved in the tricarboxylic acid cycle. However, the roles of cuproptosis-related genes (CRGs) in the clinical outcomes and immune landscape of colon cancer remain unknown.Methods: We performed bioinformatics analysis of the expression data of 13 CRGs identified from a previous study and clinical information of patients with colon cancer obtained from The Cancer Genome Atlas and Gene Expression Omnibus databases. Colon cancer cases were divided into two CRG clusters and prognosis-related differentially expressed genes. Patient data were separated into three corresponding distinct gene clusters, and the relationships between the risk score, patient prognosis, and immune landscape were analyzed. The identified molecular subtypes correlated with patient survival, immune cells, and immune functions. A prognostic signature based on five genes was identified, and the patients were divided into high- and low-risk groups based on the calculated risk score. A nomogram model for predicting patient survival was developed based on the risk score and other clinical features.Results: The high-risk group showed a worse prognosis, and the risk score was related to immune cell abundance, microsatellite instability, cancer stem cell index, checkpoint expression, immune escape, and response to chemotherapeutic drugs and immunotherapy. Findings related to the risk score were validated in the imvigor210 cohort of patients with metastatic urothelial cancer treated with anti-programmed cell death ligand 1.Conclusion: We demonstrated the potential of cuproptosis-based molecular subtypes and prognostic signatures for predicting patient survival and the tumor microenvironment in colon cancer. Our findings may improve the understanding of the role of cuproptosis in colon cancer and lead to the development of more effective treatment strategies.

Background: Laparoscopic natural orifice specimen extraction surgery (NOSES) has been widely used in colorectal neoplasms. However, only a few studies have focused on robotic NOSES. This study compared the short-term clinical outcomes and long-term survival outcomes between robotic NOSES and conventional robotic resection (CRR) groups.Methods: From March 2016 to October 2018, a consecutive of 143 patients who underwent robotic sigmoid and rectal resection at the Department of Gastrointestinal Surgery, The Second Xiangya Hospital, Central South University, were considered for inclusion in this study. Propensity-score matching (PSM) was conducted to account for differences in the baseline characteristics. After PSM, 39 patients were included in the robotic NOSES group, and 39 patients in the CRR group. The baseline characteristics between the two groups were all balanced and comparable.Results: Patients in the NOSES group experienced less intraoperative blood loss (p=0.001), lower requirements for additional analgesia (p=0.020), shorter time to first flatus (p=0.010), and a shorter time to first liquid diet (p=0.003) than the CRR group. The 3-year overall survival rates (NOSES: 92.3% vs. CRR: 89.7% p=1.000) and 3-year disease-free survival rates (NOSES: 82.1% vs. CRR: 84.6% p=0.761) between the two groups were comparable.Conclusion: Robotic natural orifice specimen extraction surgery is a safe and feasible surgery for patients with colorectal neoplasms. Robotic NOSES is associated with better short-term clinical outcomes and similar long-term survival outcomes to conventional robotic resection.

Background: Chimeric antigen receptor T cell infusion (CAR T) therapy has revolutionized the treatment of hematologic malignancies, but treatment-related toxicities are of concern. Understanding the timing and reasons for which patients present to the emergency department (ED) after CAR T therapy can assist with the early recognition and management of toxicities.Methods: A retrospective observational cohort study was conducted for patients who had undergone CAR T therapy in the past 6 months and visited the ED of The University of Texas MD Anderson Cancer Center between 04/01/2018 and 08/01/2022. The timing of presentation after CAR T product infusion, patient characteristics, and outcomes of the ED visit were examined. Survival analyses were conducted using Cox proportional hazards regression and Kaplan-Meier estimates.Results: During the period studied, there were 276 ED visits by 168 unique patients. Most patients had diffuse large B-cell lymphoma (103/168; 61.3%), multiple myeloma (21/168; 12.5%), or mantle cell lymphoma (16/168; 9.5%). Almost all 276 visits required urgent (60.5%) or emergent (37.7%) care, and 73.5% of visits led to admission to the hospital or observation unit. Fever was the most frequent presenting complaint, reported in 19.6% of the visits. The 30-day and 90-day mortality rates after the index ED visits were 17.0% and 32.2%, respectively. Patients who had their first ED visit >14 days after CAR T product infusion had significantly worse overall survival (multivariable hazard ratio 3.27; 95% confidence interval 1.29–8.27; P=0.012) than patients who first visited the ED within 14 days of CAR T product infusion.Conclusion: Cancer patients who receive CAR T therapy commonly visit the ED, and most are admitted and/or require urgent or emergent care. During early ED visits patients mainly present with constitutional symptoms such as fever and fatigue, and these early visits are associated with better overall survival.

Complex interactions between the physical environment and phenotype of a tumour, and genomics, transcriptomics, proteomics and epigenomics, are increasingly known to have a significant influence on cancer development, progression and evolution. For example, mechanical stress can alter both genome maintenance and histone modifications, which consequently affect transcription and the epigenome. Increased stiffness has been linked to genetic heterogeneity and is responsible for heterochromatin accumulations. Stiffness thereby leads to deregulation in gene expression, disrupts the proteome and can impact angiogenesis. Several studies have shown how the physics of cancer can influence diverse cancer hallmarks such as resistance to cell death, angiogenesis and evasion from immune destruction. In this review, we will explain the role that physics of cancer plays in cancer evolution and explore how multiomics are being used to elucidate the mechanisms underpinning them.

The structural maintenance of chromosome 4 (SMC4) is a member of the ATPase family of chromosomes. The most widely reported function of SMC4, as well as the remaining subunits of whole condensin complexes, is compression and dissociation of sister chromatids, DNA damage repair, DNA recombination, and pervasive transcription of the genome. Studies have also shown that SMC4 plays an exceedingly essential role in the division cycle of embryonic cells, such as RNA splicing, DNA metabolic process, cell adhesion, and extracellular matrix. On the other hand, SMC4 is also a positive regulator of the inflammatory innate immune response, while excessive innate immune responses not only disrupt immune homeostasis and may lead to autoimmune diseases, but even cancer. To further understand the expression and prognostic value of SMC4 in tumors, we provide an in-depth review of the literature and several bioinformatic databases, for example, The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), Clinical Proteomic Tumor Analysis Consortium (CPTAC), The Human Protein Atlas and Kaplan Meier plotter tools, illustrating that SMC4 plays a vital role in the occurrence and development of tumors, and high expression of SMC4 seems to consistently predict worse overall survival. In conclusion, we present this review which introduces the structure, biological function of SMC4, and its correlation with the tumor in detail; it might provide new insight into a novel tumor prognostic marker and potential tumor therapeutic target.

Anaplastic thyroid carcinoma (ATC) is a rare and aggressive form of thyroid carcinoma (TC). Currently, there are no effective treatments for this condition. In the past few years, targeted therapy and immunotherapy have made significant progress in ATC treatment. Several common genetic mutations have been found in ATC cells, involving different molecular pathways related to tumor progression, and new therapies that act on these molecular pathways have been studied to improve the quality of life of these patients. In 2018, the FDA approved dabrafenib combined with trametinib to treat BRAF-positive ATC, confirming its therapeutic potential. At the same time, the recent emergence of immunotherapy has also attracted wide attention from researchers. While immunotherapy for ATC is still in the experimental stage, numerous studies have shown that immunotherapy is a potential therapy for ATC. In addition, it has also been found that the combination of immunotherapy and targeted therapy may enhance the anti-tumor effect of targeted therapy. In recent years, there has been some progress in the study of targeted therapy or immunotherapy combined with radiotherapy or chemotherapy, showing the prospect of combined therapy in ATC. In this review, we analyze the response mechanism and potential effects of targeted therapy, immunotherapy, and combination therapy in ATC treatment and explore the future of treatment for ATC.

Introduction: In patients with limited peritoneal metastasis (PM) originating from colorectal cancer, cytoreductive surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC) is a potentially curative treatment option. This combined treatment modality using HIPEC with mitomycin C (MMC) for 90 minutes proved to be superior to systemic chemotherapy alone, but no benefit of adding HIPEC to CRS alone was shown using oxaliplatin-based HIPEC during 30 minutes. We investigated the impact of treatment temperature and duration as relevant HIPEC parameters for these two chemotherapeutic agents in representative preclinical models. The temperature- and duration- dependent efficacy for both oxaliplatin and MMC was evaluated in an in vitro setting and in a representative animal model.Methods: In 130 WAG/Rij rats, PM were established through i.p. injections of rat CC-531 colon carcinoma cells with a signature similar to the dominant treatment-resistant CMS4 type human colorectal PM. Tumor growth was monitored twice per week using ultrasound, and HIPEC was applied when most tumors were 4-6 mm. A semi-open four-inflow HIPEC setup was used to circulate oxaliplatin or MMC through the peritoneum for 30, 60 or 90 minutes with inflow temperatures of 38°C or 42°C to achieve temperatures in the peritoneum of 37°C or 41°C. Tumors, healthy tissue and blood were collected directly or 48 hours after treatment to assess the platinum uptake, level of apoptosis and proliferation and to determine the healthy tissue toxicity.Results: In vitro results show a temperature- and duration- dependent efficacy for both oxaliplatin and MMC in both CC-531 cells and organoids. Temperature distribution throughout the peritoneum of the rats was stable with normothermic and hyperthermic average temperatures in the peritoneum ranging from 36.95-37.63°C and 40.51-41.37°C, respectively. Treatments resulted in minimal body weight decrease (<10%) and only 7/130 rats did not reach the endpoint of 48 hours after treatment.Conclusions: Both elevated temperatures and longer treatment duration resulted in a higher platinum uptake, significantly increased apoptosis and lower proliferation in PM tumor lesions, without enhanced normal tissue toxicity. Our results demonstrated that oxaliplatin- and MMC-based HIPEC procedures are both temperature- and duration-dependent in an in vivo tumor model.

Introduction: Colon cancer is the 3^rd most prevalent cancer worldwide, with more than 900,000 deaths annually. Chemotherapy, targeted treatment, and immunotherapeutic treatment are the three cornerstones of colon cancer treatment; however, the occurrence of immune therapy resistance is the most pressing problem to solve. Copper is a mineral nutrient that is both beneficial and potentially toxic to cells and is increasingly implicated in cell proliferation and death pathways. Cuproplasia is characterized by copper-dependent cell growth and proliferation. This term encompasses both neoplasia and hyperplasia and describes the primary and secondary effects of copper. The connection between copper and cancer has been noted for decades. However, the relationship between cuproplasia and colon cancer prognosis remains unclear.Method: In this study, we applied bioinformatics approaches including WGCNA, GSEA and etc. to delineate cuproplasia characterization of colon cancer, set up a robust Cu_riskScore model based on cuproplasia-relevant genes and found its relevant biological processes use qRT-pCR to validate our results on our cohort.Result: The Cu_riskScore is found to be relevant to Stage and MSI-H subtype, and some biological processes including MYOGENESIS and MYC TARGETS. The Cu_riskScore high and low groups also showed different immune infiltration pattern and genomic traits. Finally, the result of our cohort showed the Cu_riskScore gene RNF113A has a marked effect in predicting immunotherapy response.Discussion: In conclusion, we identified a cuproplasia-related gene expression signature consisting of six genes and studied the landscape of the clinical and biological characterization of this model in Colon Cancer. Furthermore, the Cu_riskScore was demonstrated to be a robust prognostic indicator and predictive factor for the benefits of immunotherapy.

ALK rearrangements are identified as driver mutations in non-small-cell lung cancer (NSCLC). EML4 is the most common partner of ALK rearrangements. Here, we reported a patient with lung adenocarcinoma who was identified with EML4-ALK mutations when he progressed on an immune checkpoint inhibitor. The patient was treated with alectinib and obtained a progression-free survival (PFS) of 24 months. Then, next-generation sequencing on circulating tumor DNA identified multiple ALK mutations, including ALK G1202R, I1171N, ALK-ENC1, and EML4-ALK. Ensartinib was given, and the patient achieved a PFS of 5 months. After progression, lorlatinib was administered, and the patient achieved a partial response. Now, the benefit is still ongoing with a PFS over 10 months. Our case may provide evidence for the treatment choice of multiple ALK mutations, including ALK I1171N.

Introduction: Immune checkpoint inhibitor (ICI) is one of the standard treatment strategies in triple negative breast cancer (TNBC). However, the benefit of ICI with chemotherapy is limited in metastatic TNBC. In this study, we evaluated the effect of PD-L1 and LAG-3 expression on tissue microenvironment of mTNBC treated with ICI.Methods: We reviewed representative formalin-fixed paraffin embedded specimens from metastatic or archival tumor tissues of TNBCs who treated with PD-1/PD-L1 inhibitors in metastatic setting. We used the Opal multiplex Detection kit with six antibodies (anti-PD-L1, anti-LAG-3, anti-CD68, anti-panCK, anti-CD8, anti-CD107a/LAMP antibody).Results: We evaluated the association between LAG-3+cells and survival outcome regarding CK expression. Stromal LAG-3+/CK+ and LAG-3+/CK- cells were not associated with ICI-progression free survival(PFS) (P=0.16). However, LAG-3+ cell distributions in the tumor area impacted on ICI-PFS. A high density of LAG-3+CK+ cells was associated with shorter ICI-PFS compared with low densities of both LAG-3+CK+ and LAG-3+CK- cells (1.9 vs. 3.5 months). In addition, a high density of LAG-3+CK- cells had a relatively longer ICI-PFS compared with other groups (P=0.01). In terms of total area, the pattern of densities of LAG-3+CK+ cells and LAG-3+CK- cells were similar to those in the tumor area In addition, ICI-PFS of LAG-3+CK- and LAG-3+CK+ cell densities in the total area was equal to that in the tumor area.Discussion: In conclusion, our findings revealed tumor-intrinsic LAG-3 expression was the resistance mechanism toward PD-1/PD-L1 inhibitors in mTNBCs. Multivariate analysis also suggested that LAG-3 expression in tumor cells was an independent predictive biomarker.

Background: Cancer-associated fibroblasts (CAFs) reportedly enhance the progression of gastrointestinal surgery; however, the role of CAFs in ampullary carcinomas remains poorly examined. This study aimed to investigate the effect of CAFs on the survival of patients with ampullary carcinoma.Materials and methods: A retrospective analysis of 67 patients who underwent pancreatoduodenectomy between January 2000 and December 2021 was performed. CAFs were defined as spindle-shaped cells that expressed α-smooth muscle actin (α-SMA) and fibroblast activation protein (FAP). The impact of CAFs on survival, including recurrence-free (RFS) and disease-specific survival (DSS), as well as prognostic factors associated with survival, was analyzed.Results: The high-α-SMA group had significantly worse 5-year RFS (47.6% vs. 82.2%, p = 0.003) and 5-year DSS (67.5% vs. 93.3%, p = 0.01) than the low-α-SMA group. RFS (p = 0.04) and DSS (p = 0.02) in the high-FAP group were significantly worse than those in the low-FAP group. Multivariable analyses found that high α-SMA expression was an independent predictor of RFS [hazard ratio (HR): 3.68; 95% confidence intervals (CI): 1.21–12.4; p = 0.02] and DSS (HR: 8.54; 95% CI: 1.21–170; p = 0.03).Conclusions: CAFs, particularly α-SMA, can be useful predictors of survival in patients undergoing radical resection for ampullary carcinomas.

Introduction: Neoadjuvant stereotactic radiosurgery (NaSRS) of brain metastases has gained importance, but it is not routinely performed. While awaiting the results of prospective studies, we aimed to analyze the changes in the volume of brain metastases irradiated pre- and postoperatively and the resulting dosimetric effects on normal brain tissue (NBT).Methods: We identified patients treated with SRS at our institution to compare hypothetical preoperative gross tumor and planning target volumes (pre-GTV and pre-PTV) with original postoperative resection cavity volumes (post-GTV and post-PTV) as well as with a standardized-hypothetical PTV with 2.0 mm margin. We used Pearson correlation to assess the association between the GTV and PTV changes with the pre-GTV. A multiple linear regression analysis was established to predict the GTV change. Hypothetical planning for the selected cases was created to assess the volume effect on the NBT exposure. We performed a literature review on NaSRS and searched for ongoing prospective trials.Results: We included 30 patients in the analysis. The pre-/post-GTV and pre-/post-PTV did not differ significantly. We observed a negative correlation between pre-GTV and GTV-change, which was also a predictor of volume change in the regression analysis, in terms of a larger volume change for a smaller pre-GTV. In total, 62.5% of cases with an enlargement greater than 5.0 cm³ were smaller tumors (pre-GTV < 15.0 cm³), whereas larger tumors greater than 25.0 cm³ showed only a decrease in post-GTV. Hypothetical planning for the selected cases to evaluate the volume effect resulted in a median NBT exposure of only 67.6% (range: 33.2–84.5%) relative to the dose received by the NBT in the postoperative SRS setting. Nine published studies and twenty ongoing studies are listed as an overview.Conclusion: Patients with smaller brain metastases may have a higher risk of volume increase when irradiated postoperatively. Target volume delineation is of great importance because the PTV directly affects the exposure of NBT, but it is a challenge when contouring resection cavities. Further studies should identify patients at risk of relevant volume increase to be preferably treated with NaSRS in routine practice. Ongoing clinical trials will evaluate additional benefits of NaSRS.

Introduction: Chronic lymphocytic leukemia (CLL) is the most common adult leukemia, accounting for 30–40% of all adult leukemias. The dynamics of B-lymphocyte CLL clones with mutated immunoglobulin heavy chain variable region (IgHV) genes in their tumor (M-CLL) can be studied using mutational lineage trees.Methods: Here, we used lineage tree-based analyses of somatic hypermutation (SHM) and selection in M-CLL clones, comparing the dominant (presumably malignant) clones of 15 CLL patients to their non-dominant (presumably normal) B cell clones, and to those of healthy control repertoires. This type of analysis, which was never previously published in CLL, yielded the following novel insights. Results: CLL dominant clones undergo – or retain – more replacement mutations that alter amino acid properties such as charge or hydropathy. Although, as expected, CLL dominant clones undergo weaker selection for replacement mutations in the complementarity determining regions (CDRs) and against replacement mutations in the framework regions (FWRs) than non-dominant clones in the same patients or normal B cell clones in healthy controls, they surprisingly retain some of the latter selection in their FWRs. Finally, using machine learning, we show that even the non-dominant clones in CLL patients differ from healthy control clones in various features, most notably their expression of higher fractions of transition mutations. Discussion: Overall, CLL seems to be characterized by significant loosening – but not a complete loss – of the selection forces operating on B cell clones, and possibly also by changes in SHM mechanisms.

Tumor hypoxic environment is an inevitable obstacle for photodynamic therapy (PDT) of melanoma. Herein, a multifunctional oxygen-generating hydrogel loaded with hyaluronic acid-chlorin e6 modified nanoceria and calcium peroxide (Gel-HCeC-CaO₂) was developed for the phototherapy of melanoma. The thermo-sensitive hydrogel could act as a sustained drug delivery system to accumulate photosensitizers (chlorin e6, Ce6) around the tumor, followed by cellular uptake mediated by nanocarrier and hyaluronic acid (HA) targeting. The moderate sustained oxygen generation in the hydrogel was produced by the reaction of calcium peroxide (CaO₂) with infiltrated H₂O in the presence of catalase mimetic nanoceria. The developed Gel-HCeC-CaO₂ could efficiently alleviate the hypoxia microenvironment of tumors as indicated by the expression of hypoxia-inducible factor -1α (HIF-1α), meeting the “once injection, repeat irradiation” strategy and enhanced PDT efficacy. The prolonged oxygen-generating phototherapy hydrogel system provided a new strategy for tumor hypoxia alleviation and PDT.

There is increasing evidence that obesity is associated with the occurrence and development of malignant tumors. When studying the relationship between obesity and malignant tumors, it is very important to choose an appropriate animal model. However, BALB/c nude mice and other animals commonly used to study tumor xenograft (human-derived tumor cell lines) transplantation models are difficult to induce obesity, while C57BL/6 mice and other model animals commonly used for obesity research are not suitable for tumor xenograft transplantation. Therefore, it is difficult to replicate both obesity and malignancy in animal models at the same time. This review summarizes several experimental animal models and protocols that can simultaneously induce obesity and tumor xenografts.

Objective: It remains unclear what the best second-line treatment is for patients with small-cell lung cancer sensitive to previous platinum-based chemotherapy.Methods: We systematically screened randomized controlled trials from several online databases. The primary outcome was objective response rate (ORR), and the secondary outcomes were disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and hematological complications graded 3 to 5. The efficacy of included treatments was ranked by surface under the cumulative ranking curve (SUCRA) value.Results: We included eleven trials involving 1560 patients in quantitative analysis. Triple chemotherapy containing platinum (TP, combination of cisplatin, etoposide, and irinotecan) was associated with favorable ORR (intravenous topotecan vs TP; odds ratio: 0.13, 95% CI:0.03-0.63; SUCRA, 0.94) and PFS (vs intravenous topotecan; hazard ratio, 0.5; 95% CI: 0.25-0.99; SUCRA, 0.90). Belotecan ranked highest for OS (SUCRA, 0.90), while intravenous topotecan plus Ziv-aflibercept ranked highest for DCR (SUCRA, 0.75). TP was more likely to cause anemia and thrombocytopenia while intravenous topotecan plus Ziv-aflibercept resulted in most neutrocytopenia.Conclusion: TP is the first recommendation for the second-line treatment of sensitive relapsed SCLC. TP achieved priority in ORR and PFS with the most frequent adverse effects in anemia and thrombocytopenia. For patients who cannot tolerate the hematological adverse effects of triple chemotherapy, amrubicin is an optional option. Amrubicin had relatively good ORR and PFS, accompanied by fewer hematological complications. The rechallenge of the platinum doublet is inferior to amrubicin in ORR, DCR, and PFS. Oral topotecan has a similar effect compared with IV topotecan, but oral topotecan was associated with slightly higher safety and less stress in nursing. Belotecan contributed to the best PFS with slightly better safety but was not ideal in other outcomes.Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022358256.

Objective: Aggressive angiomyxoma (AAM) is a rare, locally aggressive soft tissue neoplasm with a marked tendency for local recurrence after surgery. Although hormone therapy, radiation therapy, and vascular embolization can be performed, we investigated the safety and efficacy of a new chemical ablation protocol for AAM.Methods: This study included two female AAM patients from 2012 to 2016. The patients’ clinical and imaging data were collected. The amount of anhydrous ethanol and glacial acetic acid used for chemical ablation was documented, and the management of any complications was detailed.Results: The maximum dimensions of the residual tumor were 12.6 cm and 14.0 cm. In one case, the lesion was in the pelvis and protruded into the vulva. Eighty milliliters of liquid with a mixture of glacial acetic acid, anhydrous ethanol, and iohexol (10:9:1) was used for chemical ablation therapy via multipoint injections with a single needle. However, a pelvic fistula developed 1 month later. In another case, the lesion was located in the abdominal wall. The ablation procedure was improved by performing chemical ablation therapy with multiple needles for multi-point injections of smaller than 30 ml injections for each procedure. To date, no recurrence or metastasis has been observed in the two cases.Conclusion: The preferred treatment for AAM is complete resection. Chemical ablation therapy is a novel adjuvant therapy for AMM. Nonetheless, more research is needed to confirm these findings.

Objectives: This study aimed to identify risk factors for recurrence in patients with cervical cancer (CC) through quantitative T1 mapping.Methods: A cohort of 107 patients histopathologically diagnosed with CC at our institution between May 2018 and April 2021 was categorized into surgical and non-surgical groups. Patients in each group were further divided into recurrence and non-recurrence subgroups depending on whether they showed recurrence or metastasis within 3 years of treatment. The longitudinal relaxation time (native T1) and apparent diffusion coefficient (ADC) value of the tumor were calculated. The differences between native T1 and ADC values of the recurrence and non-recurrence subgroups were analyzed, and receiver operating characteristic (ROC) curves were drawn for parameters with statistical differences. Logistic regression was performed for analysis of significant factors affecting CC recurrence. Recurrence-free survival rates were estimated by Kaplan–Meier analysis and compared using the log-rank test.Results: Thirteen and 10 patients in the surgical and non-surgical groups, respectively, showed recurrence after treatment. There were significant differences in native T1 values between the recurrence and non-recurrence subgroups in the surgical and non-surgical groups (P0.05). The areas under the ROC curve of native T1 values for discriminating recurrence of CC after surgical and non-surgical treatment were 0.742 and 0.780, respectively. Logistic regression analysis indicated that native T1 values were risk factors for tumor recurrence in the surgical and non-surgical groups (P=0.004 and 0.040, respectively). Compared with cut-offs, recurrence-free survival curves of patients with higher native T1 values of the two groups were significantly different from those with lower ones (P=0.000 and 0.016, respectively).Conclusion: Quantitative T1 mapping could help identify CC patients with a high risk of recurrence, supplementing information on tumor prognosis other than clinicopathological features and providing the basis for individualized treatment and follow-up schemes.