Hasil untuk "Neoplasms. Tumors. Oncology. Including cancer and carcinogens"

Camille Jimenez Cortes, Philippe Lalanda, German Vega

Predicting drug response in patients from preclinical data remains a major challenge in precision oncology due to the substantial biological gap between in vitro cell lines and patient tumors. Rather than aiming to improve absolute in vitro prediction accuracy, this work examines whether explicitly separating representation learning from task supervision enables more sample-efficient adaptation of drug-response models to patient data under strong biological domain shift. We propose a staged transfer-learning framework in which cellular and drug representations are first learned independently from large collections of unlabeled pharmacogenomic data using autoencoder-based representation learning. These representations are then aligned with drug-response labels on cell-line data and subsequently adapted to patient tumors using few-shot supervision. Through a systematic evaluation spanning in-domain, cross-dataset, and patient-level settings, we show that unsupervised pretraining provides limited benefit when source and target domains overlap substantially, but yields clear gains when adapting to patient tumors with very limited labeled data. In particular, the proposed framework achieves faster performance improvements during few-shot patient-level adaptation while maintaining comparable accuracy to single-phase baselines on standard cell-line benchmarks. Overall, these results demonstrate that learning structured and transferable representations from unlabeled molecular profiles can substantially reduce the amount of clinical supervision required for effective drug-response prediction, offering a practical pathway toward data-efficient preclinical-to-clinical translation.

Shanliang Ye, Yong Peng, Wenhang Zhuang et al.

BackgroundAfferent loop obstruction (ALO) is an uncommon but potentially life-threatening complication following Billroth II gastrectomy, with an estimated incidence of around 1%. It often presents with nonspecific symptoms such as postprandial vomiting and jaundice, making timely diagnosis and effective treatment crucial. Minimally invasive endoscopic techniques have emerged as promising alternatives to surgery.Case presentationWe report the case of a 63-year-old woman with a history of Billroth II gastrectomy for gastric cancer who presented with progressive jaundice, nausea, and vomiting. Imaging revealed significant duodenal wall thickening consistent with ALO. Conventional endoscopic attempts to traverse the obstructed segment failed due to severe luminal narrowing and tortuosity. Under combined endoscopic and interventional radiologic guidance, a duodenal self-expanding metal stent was successfully deployed across the stricture, resulting in immediate symptom relief and biochemical improvement.ConclusionInterventional-guided endoscopic stent placement is a safe, effective, and minimally invasive approach for managing malignant or benign ALO in post-gastrectomy patients. This hybrid technique may be particularly valuable in anatomically complex or surgically high-risk cases.

Batorov Egor V., Ostanin Alexander, Chernykh Elena

The effectiveness of anti-PD-1/PD-L1 targeted therapies focused on the antitumor immune response restoration in the treatment of melanoma and several other tumors has renewed trust in immunotherapy potential. Despite inspiring enthusiasm that led both to the expansion of indications for anti-PD-1/PD-L1 monoclonal antibodies and to an explosive growth in trials of new immune checkpoint inhibitors, a number of unresolved problems remain: relatively low response rates to existing drugs, development of acquired resistance, tumor progression and immune-mediated adverse events. Both the response to anti-checkpoint therapy and possible adverse reactions are based on quantitative and functional changes in malignant cell clones, tumor microenvironment and immune cells. An indispensable role in these interactions is played by regulatory T cells (Tregs), a heterogeneous population of CD4+ T lymphocytes capable of suppressing the immune response. It is known that, like conventional T cells, Tregs up-regulate several checkpoint receptors, including PD-1, TIM-3, LAG-3. However, the biological relevance of such expression and the consequences of Treg checkpoint blockade are vague, as data from in vitro and clinical observations are contradictory. Here, we reviewed the current understanding of inhibitory checkpoint receptor expression by Treg populations and their relationship with the effects of treatment with checkpoint inhibitors.

Yijiao Ning, Junhao Mu, Zhao Zhang et al.

Abstract Objective To understand the baseline characteristics and changing trends of pancreatic cancer mortality and disease burden, we statistically analyze the mortality data among Chinese residents from 2008 to 2021. Methods Pancreatic cancer mortality data were selected from China Cause of Death Surveillance Dataset. We calculated Crude Mortality Rate (CMR), age-standardized mortality rate (ASMR), potential years of life lost (PYLL), and PYLL rate (PYLLR) stratified by sex, age, urban/rural residence, and region (eastern/central/western China). The average annual percentage change (AAPC) was used to quantify trends in ASMR and PYLLR. Chi-square tests (R4.4.3) assessed mortality differences across subgroups, while an age-period-cohort (APC) model analyzed the effects of age, period, and birth cohort on mortality trends. Results The ASMR of pancreatic cancer in China increased from 3.67/100,000 in 2008 to 4.45/100,000 in 2021 (AAPC = 1.09%), while PYLLR rose from 0.23% to 0.35% (AAPC = 3.13%). Subgroup disparities: Both ASMR and PYLLR were higher in males than females, urban than rural areas, and eastern > central > western regions. Burden acceleration: The fastest increases occurred in males (vs. females), rural (vs. urban), and western > central > eastern regions. Conclusion Pancreatic cancer mortality and disease burden in China show a sustained upward trend, disproportionately affecting older adults, males, urban residents, and eastern populations. Rapid escalation in males, rural areas, and western regions underscores the need for targeted interventions.

Shannon R. Stock, Joshua A. Parrish, Michael T. Burns et al.

ABSTRACT Purpose Accurate classification of prostate cancer (PC) disease states defined by the presence or absence of metastasis and castration resistance (CRPC) is critical but challenging in population‐based research. As chart review is not feasible on a large scale, accurate automated methods are needed. Methods We conducted a retrospective study using data from the Veterans Affairs Health Care System to evaluate algorithms for identifying CRPC and metastatic PC, with manual chart review as the gold standard. Our analysis included 8336 patients for CRPC classification and 721 for metastatic disease classification. For CRPC classification, we assessed one novel algorithm using criteria including rising prostate‐specific antigen levels or progression to metastatic disease while receiving androgen deprivation therapy or initiating CRPC‐specific treatments. For metastatic disease detection, we assessed four algorithms based on: ICD codes alone, natural language processing (NLP) alone, a novel algorithm combining ICD codes and treatment patterns, and an enhanced version of the novel algorithm integrating NLP, evaluating the sensitivity and specificity of each. Positive and negative predictive values were reported across a range of assumed disease prevalence. Results Out of 8336 patients with PC, 1190 (14.3%) were identified as having CRPC through chart review, with the CRPC algorithm achieving 85.1% sensitivity and 96.1% specificity. Among 721 patients evaluated for metastatic disease, 179 (24.8%) were identified as having metastatic disease through chart review. The algorithm combining ICD codes, treatment patterns, and NLP demonstrated the highest sensitivity (94.4%) and high specificity (93.0%), while other methods had lower sensitivity with varied specificity. Conclusions Our findings suggest that our CRPC algorithm and the combined ICD codes, treatment patterns, and NLP algorithm for metastasis are effective automated approaches for identifying advanced states of PC. In particular, integrating NLP boosted sensitivity for metastatic classification with minimal specificity trade‐off, highlighting the value of a multifaceted approach to large‐scale PC research.

Agnar Martin Bjørnstad, Elias Stenhede, Arian Ranjbar

Accurate tumor size measurement is a cornerstone of evaluating cancer treatment response. The most widely adopted standard for this purpose is the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, which relies on measuring the longest tumor diameter in a single plane. However, volumetric measurements have been shown to provide a more reliable assessment of treatment effect. Their clinical adoption has been limited, though, due to the labor-intensive nature of manual volumetric annotation. In this paper, we present Lite ENSAM, a lightweight adaptation of the ENSAM architecture designed for efficient volumetric tumor segmentation from CT scans annotated with RECIST annotations. Lite ENSAM was submitted to the MICCAI FLARE 2025 Task 1: Pan-cancer Segmentation in CT Scans, Subtask 2, where it achieved a Dice Similarity Coefficient (DSC) of 60.7% and a Normalized Surface Dice (NSD) of 63.6% on the hidden test set, and an average total RAM time of 50.6 GBs and an average inference time of 14.4 s on CPU on the public validation dataset.

Maria Vittoria Chiaruttini, Lukas Pin, Sofia S. Villar

The majority of response-adaptive randomisation (RAR) designs in the literature rely on efficacy data to guide dynamic patient allocation. However, their applicability becomes limited in settings where efficacy outcomes, such as survival, are observed with a random delay. To address this limitation, we introduce SAFER, a novel RAR design that leverages early-emerging safety data to inform treatment allocation decisions, particularly in oncology trials. The design is broadly applicable to contexts where prioritizing the arm with a superior safety is desirable. This is especially relevant in non-inferiority trials, to demonstrate that an experimental treatment is not inferior to the standard of care, while potentially offering improved tolerability. In such trials, an unavoidable trade-off arises: maintaining statistical efficiency for the efficacy hypothesis while integrating safety-driven adaptations through RAR. The SAFER design addresses this trade-off by dynamically adjusting the allocation proportion based on the observed association between safety and efficacy endpoints. We illustrate the performance of SAFER through a simulation study inspired by the CAPP-IT Phase III oncology trial. Results show that SAFER preserves statistical power, reduces the adverse event rate, and offers flexible adaptation speed depending on the temporal alignment of the endpoints.

Jonas Weidner, Ivan Ezhov, Michal Balcerak et al.

Butterfly tumors are a distinct class of gliomas that span the corpus callosum, producing a characteristic butterfly-shaped appearance on MRI. The distinctive growth pattern of these tumors highlights how white matter fibers and structural connectivity influence brain tumor cell migration. To investigate this relation, we applied biophysical tumor growth models to a large patient cohort, systematically comparing models that incorporate fiber tract information with those that do not. Our results demonstrate that including fiber orientation data significantly improves model accuracy, particularly for a subset of butterfly tumors. These findings highlight the critical role of white matter architecture in tumor spread and suggest that integrating fiber tract information can enhance the precision of radiotherapy target volume delineation.

Xueying Chen, Jianfeng Ke, Lauren Flynn et al.

Purpose: Hereditary cancer risk is key to guiding screening and prevention strategies. Cancer risks can vary by individual due to the presence or absence of high- and moderate-risk pathogenic variants (PV) in cancer-associated genes, in addition to sex, age, and other risk factors. We previously developed Fam3PRO, a flexible multi-gene, multi-cancer Mendelian risk prediction model that estimates a patient's risk of carrying a PV in hereditary cancer genes and their future risk of developing several types of cancer. The Fam3PRO R package includes 22 genes with 18 associated cancers, allowing users to build customized sub-models from any gene-cancer set. However, the current R package lacks a user interface (UI), limiting its practical use in clinical settings. Therefore, we aim to develop a web-based UI for broader use of the Fam3PRO functionalities. Methods: The Fam3PRO UI (F3PI), built with R Shiny, collects and formats inputs including family health history, genetic test results, and other risk factors. Pedigree data are interactively visualized and modified via pedigreejs, while the backend Fam3PRO model takes all the inputs to generate carrier probabilities and future cancer risks, presented through an interactive UI. Results: F3PI streamlines the collection of patient and family history data, which is analyzed by the Fam3PRO models to provide personalized cancer risks for each proband across 18 cancers, as well as probabilities that a proband has a PV in up to 22 hereditary cancer genes. These results are returned to the user, within one minute on average and are available in both interactive and downloadable formats. Conclusion: We have developed F3PI, an easy-to-use, interactive web application that makes cancer and genetic risk information more accessible to providers and their patients.

Danai Dima, Nerea Lopetegui‐Lia, Olisaemeka Ogbue et al.

Abstract Background Both immunotherapy (IO) and targeted therapy (TT) are used as adjuvant (adj) treatment for stage III melanoma, however, data describing real‐world outcomes are limited. In addition, a significant proportion of patients relapse, for whom best management is unclear. The aim of our study was to assess the efficacy, and safety of adj anti‐PD1 IO and TT in a real‐world cohort of patients with resected stage III melanoma, and further delineate patterns of recurrence and treatment strategies. Methods We retrospectively analyzed 130 patients who received adj therapy (100 anti‐PD1 IO and 30 TT). Results At a median follow‐up of 30 months, median relapse‐free survival (RFS) was 24.6 (95% CI, 17–not reached [NR]) versus 64 (95% CI, 29.5–NR) months for the TT and IO groups, respectively (p = 0.26). Median overall survival (OS) was NR for either subgroup. At data cutoff, 77% and 82% of patients in TT and IO arms were alive. A higher number of grade ≥3 treatment‐related adverse events (AEs) were noted in the IO group (11% vs. 3%), however, a higher proportion of patients permanently discontinued adj therapy in the TT group (43% vs. 11%) due to toxicity. Strategies at relapse and outcomes were variable based on location and timing of recurrence. A significant number of patients who relapsed after adj IO received a second round of IO. Among them, patients who were off adj IO at relapse had superior second median RFS (mRFS2), compared to those who relapsed while on adj IO; mRFS2 was NR versus 5.1 months (95% CI, 2.5–NR), respectively, p = 0.02. Conclusion In summary, both TT and IO yielded prolonged RFS in a real‐world setting, however, longer follow‐up is needed to determine any potential OS benefit. Adj therapy, particularly TT, may not be as well tolerated as suggested in clinical trials, with lower completion rates (59% vs. 74%) in a real‐life setting. Overall, patients who relapse during adj therapy have poor outcomes, while patients who relapse after discontinuation of adj IO therapy appear to benefit from IO re‐treatment.

Christian Idel, Jonas Fleckner, Kirstin Plötze-Martin et al.

Abstract Background Head and neck squamous cell carcinoma (HNSCC) represents a common and heterogeneous malignancy of the oral cavity, pharynx and larynx. Surgery and radio(chemo)therapy are the standard treatment options and also have great influence on the composition of the tumor microenvironment and immune cell functions. However, the impact of radio(chemo)therapy on the distribution and characteristics of circulating monocyte subsets in HNSCC are not fully understood. Methods Expression patterns of adhesion molecules and chemokine receptors CD11a (integrin-α L; LFA-1), CD11b (integrin-α M; Mac-1), CD11c (integrin-α X), CX3CR1 (CX3CL1 receptor) and checkpoint molecule PD-L1 (programmed cell death ligand-1) were investigated upon radio(chemo)therapeutic treatment using flow cytometry. Furthermore, comprehensive analysis of plasma cytokines was performed before and after treatment using ELISA measurements. Results Our data reveal a partial recovery of circulating monocytes in HNSCC patients upon radio(chemo)therapeutic treatment, with differential effects of the individual therapy regimen. PD-L1 expression on non-classical monocytes significantly correlates with the individual plasma levels of chemokine CXCL11 (C-X-C motif chemokine 11). Conclusions Further comprehensive investigations on larger patient cohorts are required to elucidate the meaningfulness of peripheral blood monocyte subsets and chemokine CXCL11 as potential bioliquid indicators in HNSCC with regard to therapy response and the individual immunological situation.

Joshua P. Schiff, Borna Maraghechi, Re-I. Chin et al.

We conducted a prospective pilot study evaluating the feasibility of same day MRI-only simulation and treatment with MRI-guided adaptive palliative radiotherapy (MAP-RT) for urgent palliative indications (NCT#03824366). All (16/16) patients were able to complete 99% of their first on-table attempted fractions, and no grades 3–5 toxicities occurred.

Jiaolin Zhou, Guole Lin

Yulin Peng, Yan Wang, Ning Tang et al.

Min Huang, Guillermo N Dalton, Won-Ju Kim et al.

LIU Yixin, XU Tianzi, NING Biao et al.

Objective To investigate the effect of Sema6D knockdown on the proliferation, migration, invasion and angiogenesis-promoting ability of human osteosarcoma cell lines. Methods The expression of Sema6D in clinical tissues and cell lines of human osteosarcoma was detected. After the targeted siRNA transfection, the changes of proliferation, migration and invasion were measured by CCK-8, wound healing and Transwell experiments. HUVECs were co-cultured with tumor conditioned medium to detect their tube formation ability. And the expression of signal pathway proteins was detected by Western blot. Results Sema6D was highly expressed in human osteosarcoma tissues and cell lines(P < 0.05). After silencing Sema6D, the proliferation, migration and invasion of 143B and MG63 cells decreased significantly(P < 0.05), the angiogenesis ability of HUVECs decreased in vitro(P < 0.01), and the expression of PI3K/AKT/mTOR and ERK-related signal pathway proteins decreased(P < 0.05). Conclusion Sema6D is overexpressed in human osteosarcoma tissues and cell lines. Knockdown of Sema6D expression level could inhibit the proliferation, migration, invasion and angiogenesis-promoting ability of human osteosarcoma cells via reducing PI3K/AKT/mTOR and ERK signal pathway.

Zheng Chen, Lingwei Zhu, Ziwei Yang et al.

Cancer subtyping is crucial for understanding the nature of tumors and providing suitable therapy. However, existing labelling methods are medically controversial, and have driven the process of subtyping away from teaching signals. Moreover, cancer genetic expression profiles are high-dimensional, scarce, and have complicated dependence, thereby posing a serious challenge to existing subtyping models for outputting sensible clustering. In this study, we propose a novel clustering method for exploiting genetic expression profiles and distinguishing subtypes in an unsupervised manner. The proposed method adaptively learns categorical correspondence from latent representations of expression profiles to the subtypes output by the model. By maximizing the problem -- agnostic mutual information between input expression profiles and output subtypes, our method can automatically decide a suitable number of subtypes. Through experiments, we demonstrate that our proposed method can refine existing controversial labels, and, by further medical analysis, this refinement is proven to have a high correlation with cancer survival rates.

Hsiang-Wei Huang, Wen-Tsung Huang, Hsun-Heng Tsai

Ki-67 is a nuclear protein that can be produced during cell proliferation. The Ki67 index is a valuable prognostic variable in several kinds of cancer. In breast cancer, the index is even routinely checked in many patients. Currently, pathologists use the immunohistochemistry method to calculate the percentage of Ki-67 positive malignant cells as Ki-67 index. The higher score usually means more aggressive tumor behavior. In clinical practice, the measurement of Ki-67 index relies on visual identifying method and manual counting. However, visual and manual assessment method is timeconsuming and leads to poor reproducibility because of different scoring standards or limited tumor area under assessment. Here, we use digital image processing technics including image binarization and image morphological operations to create a digital image analysis method to interpretate Ki-67 index. Then, 10 breast cancer specimens are used as validation with high accuracy (correlation efficiency r = 0.95127). With the assistance of digital image analysis, pathologists can interpretate the Ki67 index more efficiently, precisely with excellent reproducibility.

Han-Hsing Tsou, Hong-Chieh Tsai, C. Chu et al.

Simple Summary Oral squamous cell carcinoma (OSCC) is one of the most common smoking-related cancer types in the world. Better understanding of the pathophysiology of OSCC would lead to the development of novel therapeutic options. The epidermal growth factor receptor (EGFR) pathway plays a crucial role in the development of OSCC, and aberrant EGFR expression levels have been associated with smoking. Cigarette smoke contains large amounts of aldehydes such as acrolein, which is a highly reactive environmental toxin. In this study, our results present that acrolein is important in oncogenic transformation through activating the EGFR signaling pathway, contributing to oral carcinogenesis. To the best of our knowledge, this is the first study to provide molecular evidence, showing that cigarette smoke containing acrolein contributes to EGFR amplification and activation of downstream signaling in OSCC. Thus, acrolein might be a novel target for early detection and prevention of oral cancer in the future. Abstract Oral squamous cell carcinoma (OSCC) accounts for 80–90% of all intraoral malignant neoplasms. The single greatest risk factor for oral cancer is tobacco use, including cigarettes, cigars, chewing tobacco, and snuff. Aberrations of the epidermal growth factor receptor (EGFR) pathway features prominently in oral tumorigenesis and progression. It was shown that cigarette smoking (CS) is associated with worse prognosis in OSCC patients and overexpression of EGFR in tumor tissue. However, the mechanism by which cigarette smoking induced EGFR pathway activation remains to be fully elucidated. Acrolein, an IARC group 2A carcinogen, is a highly reactive aldehyde found in CS. Here we report that acrolein is capable of inducing tumorigenic transformation in normal human oral keratinocytes (NOK). The acrolein-transformed NOK cells showed EGFR copy number amplification, increased EGFR expression, and activation of downstream ERK and AKT signaling pathway. No p53 mutations were observed in acrolein-transformed NOK cells. Inhibiting EGFR pathway using an anti-EGFR antibody, cetuximab, inhibits tumor growth. Furthermore, by examining tissue sample from patients, we found an increased EGFR copy number was positively associated with acrolein-induced DNA damages in OSCC patients. Taken together, our results indicate that acrolein is important in tumorigenic transformation through amplification of EGFR and activating the downstream signaling pathway, contributing to oral carcinogenesis. This is the first study to provide molecular evidence showing that CS containing acrolein contributes to EGFR amplification in OSCC.

Magda Zanelli, Francesca Sanguedolce, Maurizio Zizzo et al.

Abstract Background Primary effusion lymphoma is a rare, aggressive large B-cell lymphoma strictly linked to infection by Human Herpes virus 8/Kaposi sarcoma-associated herpes virus. In its classic form, it is characterized by body cavities neoplastic effusions without detectable tumor masses. It often occurs in immunocompromised patients, such as HIV-positive individuals. Primary effusion lymphoma may affect HIV-negative elderly patients from Human Herpes virus 8 endemic regions. So far, rare cases have been reported in transplanted patients. The purpose of our systematic review is to improve our understanding of this type of aggressive lymphoma in the setting of transplantation, focusing on epidemiology, clinical presentation, pathological features, differential diagnosis, treatment and outcome. The role of assessing the viral serological status in donors and recipients is also discussed. Methods We performed a systematic review adhering to the PRISMA guidelines. The literature search was conducted on PubMed/MEDLINE, Web of Science, Scopus, EMBASE and Cochrane Library, using the search terms “primary effusion lymphoma” and “post-transplant”. Results Our search identified 13 cases of post-transplant primary effusion lymphoma, predominantly in solid organ transplant recipients (6 kidney, 3 heart, 2 liver and 1 intestine), with only one case after allogenic bone marrow transplantation. Long-term immunosuppression is important in post-transplant primary effusion lymphoma commonly developing several years after transplantation. Kaposi Sarcoma occurred in association with lymphoma in 4 cases of solid organ recipients. The lymphoma showed the classical presentation with body cavity effusions in absence of tumor masses in 10 cases; 2 cases presented as solid masses, lacking effusions and one case as effusions associated with multiple organ involvement. Primary effusion lymphoma occurring in the setting of transplantation was more often Epstein Barr-virus negative. The prognosis was poor. In addition to chemotherapy, reduction of immunosuppressive treatment, was generally attempted. Conclusions Primary effusion lymphoma is a rare, but often fatal post-transplant complication. Its rarity and the difficulty in achieving the diagnosis may lead to miss this complication. Clinicians should suspect primary effusion lymphoma in transplanted patients, presenting generally with unexplained body cavity effusions, although rare cases with solid masses are described.