bims-netuvo Biomed News
on Nerves in tumours of visceral organs
Issue of 2025–11–16
sixteen papers selected by
Maksym V. Kopanitsa, Charles River Laboratories
  1. Small cell lung cancer induces synaptic scaling to alter neuronal excitability.
  2. Neuron-tumor crosstalk fuels small cell lung cancer.
  3. LRP1 regulates GDNF secretion and perineural invasion in pancreatic cancer via PI3K/AKT signaling.
  4. Slc26a9 promotes the perineural invasion of pancreatic cancer in mice.
  5. Clinical significance of quantification of perineural cancer invasion on MRI-targeted prostate biopsy.
  6. Malignant peripheral nerve sheath tumors in schwannomatosis: a case series.
  7. Perineural and Lymphovascular Invasion in Resected Pancreatic Ductal Adenocarcinoma: A High-Risk Subgroup That Could Benefit from Adjuvant Radiotherapy.
  8. Malignant peripheral nerve sheath tumors in schwannomatosis: systematic review and meta-analysis.
  9. CLCF1 is associated with perineurial invasion and prognosis in colorectal cancer.
  10. Perineural invasion as both a prognostic factor for stage II rectal cancer and an indicator for adjuvant chemotherapy.
  11. ASO Visual Abstract: Perineural Invasion Worsens Long-Term Outcome of Pancreatic Neuroendocrine Tumors following Surgical Resection.
  12. Development and validation of a novel nerve-related prognostic model for gastric cancer based on bulk and single-cell RNA sequencing data.
  13. Imaging Insights into Perineural Tumor Spread.
  14. Improving detection of cancer-related cognitive impairment (CRCI) in non-CNS cancer: current trends and future directions.
  15. Is the risk of brain metastasis and prognosis different in HER2-low breast cancer?
  16. Association of neuronal autoantibodies with overall survival in gastric cancer patients.
  1. Commun Biol. 2025 Nov 13. 8(1): 1559
    Small cell lung cancer induces synaptic scaling to alter neuronal excitability.
    Aiden J Houcek, Burak Uzay, Geena V Ildefonso, Tolu Omokehinde, Lisa M Monteggia, Vito Quaranta, Amanda Linkous, Ege T Kavalali.
      Tumor cell plasticity in novel microenvironments is central to the integration and subsequent growth of metastatic cells. However, the functional consequences of tumor cell integration with central neurons remains understudied. Here, we address this question using small cell lung cancer (SCLC), which has an extraordinary propensity to metastasize to the brain in humans. Transcriptomic and electrophysiological analysis of SCLC cells in neuronal microenvironments reveal a heterogeneous population of synapse-forming SCLC cells with neurons. While a proportion of neuron-SCLC synapses are blocked by AMPA receptor antagonists, we also find a sensitivity of these synapses to GABAA receptor inhibition. The functional integration of SCLC with central neurons induced multiplicative synaptic upscaling between neurons and dysregulated neuronal excitability. Aberrant excitation in human neurons with SCLC was sustained by synaptic NMDA receptor activation and can be reduced by the FDA approved NMDA receptor blocker memantine. These findings reveal strategies to normalize tumor-induced exacerbation of aberrant neuronal activity.
    DOI:  https://doi.org/10.1038/s42003-025-09006-7
  2. Trends Pharmacol Sci. 2025 Nov;pii: S0165-6147(25)00231-7. [Epub ahead of print]46(11): 1041-1043
    Neuron-tumor crosstalk fuels small cell lung cancer.
    Canhui Cao.
      Small cell lung cancer (SCLC) progression relies on neuronal activity, yet the mechanisms remain unclear. Two recent studies by Savchuk et al. and Sakthivelu et al. reveal that SCLC co-opts vagal and sympathetic inputs and forms glutamatergic or GABAergic synapse-like connections with neurons, uncovering direct neuron-tumor crosstalk as a key driver of malignancy and a potential therapeutic vulnerability.
    Keywords:  nervous system; neuron–cancer crosstalk; receptors; small cell lung cancer; vagus nerve
    DOI:  https://doi.org/10.1016/j.tips.2025.10.007
  3. Cell Signal. 2025 Nov 09. pii: S0898-6568(25)00640-0. [Epub ahead of print] 112225
    LRP1 regulates GDNF secretion and perineural invasion in pancreatic cancer via PI3K/AKT signaling.
    Songmei Lou, Shenhao Liu, Mengying Zhu, Jia Xu, Jin Chen, Mengli Wu, Xiaoming Wu, Bin Xu, Jian Xu.
      Pancreatic cancer induces intense abdominal pain through the infiltration of cancer cells into surrounding nerve tissues, leading to sensory neuron damage. The research aims to identify pivotal molecules involved in PNI, contributing to clinical strategies that alleviate pain and enhance the quality of life for patients. This study used shRNA interference lentivirus to downregulate LRP1 expression in pancreatic cancer and neural cells, comparing perineural invasion (PNI) and neurotrophic factor level changes. An in vitro co-culture model of pancreatic cancer cells with dorsal root ganglia (DRG) assessed the impact of reduced LRP1 on DRG synaptic growth. Additionally, an animal model of neural invasion studied the effects of LRP1 downregulation on neural function. The mutual attraction between Panc-1 and SK-N-SH cells was suppressed upon the downregulation of LRP1 levels in both cell lines. Subsequent investigations revealed a reduction in the autocrine and paracrine secretion of neurotrophic factors and their receptors between Panc-1 and SK-N-SH with the decrease in LRP1 levels. At the tissue level, a significant inhibition of DRG growth was observed. The reduction of LRP1 expression effectively inhibits pancreatic cancer PNI. Concurrently, levels of neurotrophic factors and their receptors in the tumor-neural microenvironment decrease. Mechanistically, LRP1 knockdown suppressed PI3K/AKT and ERK signaling pathways, leading to reduced GDNF secretion and impaired perineural invasion. LRP1 may act as an important molecule in modulating communication between pancreatic cancer cells and neural tissues. Our study offers new potential targets for the treatment of pancreatic cancer neural invasion.
    Keywords:  LRP1; PNI; Pancreatic cancer; Tumor-neural microenvironment
    DOI:  https://doi.org/10.1016/j.cellsig.2025.112225
  4. Biochem Biophys Res Commun. 2025 Nov 08. pii: S0006-291X(25)01668-7. [Epub ahead of print]791 152952
    Slc26a9 promotes the perineural invasion of pancreatic cancer in mice.
    Bohan Hua, Xiaogeng Huang, Liping Chen, Yuhua Li, Dashan Lu, Dongjie Wang, Yujing Chen, Huadong Ni, Ming Yao, Chaobo Ni.
      Perineural invasion (PNI) is a pivotal prognostic factor in pancreatic ductal adenocarcinoma (PDAC), associated with aggressive tumor behavior and poor patient outcomes. This study investigated the role of Slc26a9 in regulating peripheral nerve invasion in pancreatic cancer. Bioinformatic analysis of GEO datasets showed markedly higher Slc26a9 expression in PNI-positive patients than in those without PNI. A PDAC model was established by implanting Panc02-luc cells into C57BL/6 mice. Abdominal mechanical hyperalgesia, hunching behavior, and anxiety-like behaviors were assessed using von Frey, hunch-score, and open field tests. PNI in pancreatic tissue was evaluated by immunohistochemistry. On postoperative days 7, 14, and 21, PDAC mice exhibited significantly increased tumor volume and weight, and decreased spleen weight (days 14 and 21) compared to the sham group. By day 21, body weight was also significantly reduced. On day 7, there were no significant differences in mechanical sensitivity, hunch scores, or anxiety-like behaviors, and no PNI was observed. By day 14, PDAC mice showed marked increases in pain, hunch scores, and anxiety-like behaviors, accompanied by evidence of PNI. To further explore the mechanism, we engineered a Slc26a9-overexpressing Panc02 cell line. Transwell and scratch assays demonstrated that Slc26a9 overexpression promotes Panc02 cell migration in vitro. In vivo, mice implanted with Slc26a9-overexpressing cells exhibited pronounced abdominal mechanical hyperalgesia, elevated hunch scores, and anxiety-like behaviors as early as day 7, along with confirmed PNI in the pancreas. These results suggest that Slc26a9 facilitates PNI in pancreatic cancer and may serve as a promising therapeutic target.
    Keywords:  Pain; Pancreatic cancer; Perineural invasion; Slc26a9; panc02
    DOI:  https://doi.org/10.1016/j.bbrc.2025.152952
  5. Diagn Pathol. 2025 Nov 10. 20(1): 126
    Clinical significance of quantification of perineural cancer invasion on MRI-targeted prostate biopsy.
    Madhurya Ramineni, Ying Wang, Hiroshi Miyamoto.
       BACKGROUND: MRI-targeted biopsy (T-Bx) has considerably improved the detection of clinically significant prostate cancer, while the clinical impact of perineural invasion (PNI) seen on T-Bx remains unclear. We aimed to determine the prognostic significance of PNI quantification on T-Bx.
    METHODS: We assessed 169 consecutive patients undergoing T-Bx, along with systematic biopsy, and subsequent radical prostatectomy by quantifying actual PNI foci on T-Bx and comparing their postoperative oncologic outcomes.
    RESULTS: No PNI was detected on T-Bx in 136 (80.5%) cases, whereas 1 (n = 18; 10.7%), 2 (n = 7; 4.1%), 3 (n = 5; 3.0%), and 4 (n = 3; 1.8%) foci of PNI were present on T-Bx of the remaining cases. Compared to cases with no PNI, those exhibiting single PNI had significantly higher pT stage and significantly higher incidence of lymph node metastasis. However, there were no significant differences in any of the clinicopathologic features examined, including tumor grade, stage, and volume, between cases with single vs. multifocal PNI. Univariate survival analysis revealed a significantly higher risk of biochemical recurrence following prostatectomy in patients with PNI (vs. no PNI; P < 0.001) or multifocal PNI (vs. single PNI; P = 0.043) on T-Bx. Differences in recurrence-free survival between 0 vs. 1 PNI (P = 0.176), 1 vs. 2 PNI (P = 0.187), and 2 vs. 3-4 PNI (P = 0.939) were not statistically significant. In multivariable analyses, multifocal PNI (vs. single PNI) on T-Bx showed significance for the risk of postoperative recurrence (hazard ratio 4.922 or 6.173, P < 0.05).
    CONCLUSIONS: Multifocal PNI on T-Bx was found to be associated with significantly poorer oncologic outcomes, as an independent predictor, in men with prostate cancer undergoing radical prostatectomy. PNI quantification on T-Bx may thus provide useful information for the more accurate risk stratification of prostate cancer.
    Keywords:  Perineural invasion; Prognosis; Prostate cancer; Radical prostatectomy; Targeted biopsy
    DOI:  https://doi.org/10.1186/s13000-025-01728-w
  6. J Neurosurg. 2025 Nov 14. 1-9
    Malignant peripheral nerve sheath tumors in schwannomatosis: a case series.
    Ken Porche, Kirsten M Hayford, Chloe Gui, Suganth Suppiah, Robert J Spinner.
       OBJECTIVE: Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive sarcomas predominantly associated with neurofibromatosis type 1 (NF1). However, their occurrence within NF type 2 (NF2)-related and SMARCB1-related schwannomatosis remains rare and poorly characterized. Accurate and timely diagnosis is challenging due to clinical and radiological similarities with benign schwannomas, potentially delaying appropriate management and impacting outcomes. This study presents an institutional case series aiming to better characterize the clinical presentations specifically for MPNSTs arising in patients with NF2- and SMARCB1-related schwannomatosis.
    METHODS: This retrospective case series included patients diagnosed with schwannomatosis who subsequently developed histopathologically confirmed MPNSTs. Conducted at Mayo Clinic (Rochester, Minnesota) and University Health Network (Toronto, Canada), the study spanned January 1, 2003, to November 1, 2024. Patients were selected based on clinical or genetic diagnoses of schwannomatosis using International Consensus Group on Neurofibromatosis Diagnostic Criteria. Comprehensive clinical, radiological, and pathological data, including demographics, presenting symptoms, tumor features (size, location, immunohistochemistry, genetics), treatments (resection, chemotherapy, radiotherapy), and follow-up outcomes were extracted from electronic medical records.
    RESULTS: The authors identified 8 patients with a mean age of 36 years, half of whom had NF2-related schwannomatosis. The most common presenting symptom was pain (71%). The mean tumor size was 8.2 ± 7.0 cm, with gross-total resection being the most common surgical treatment (67%), typically supplemented with radiation therapy (78%). More than half of the patients (56%) exhibited metastatic disease, and all tumors with reported grading were Fédération Nationale des Centres de Lutte Contre le Cancer grade 3. No tumors were associated with LZTR1 mutations. One notable case involved a 39-year-old male with SMARCB1-related schwannomatosis who had a femoral MPNST resected 13 years prior and subsequently developed a sciatic nerve MPNST that was managed successfully with neoadjuvant chemotherapy, radiation therapy, and negative margin resection. Of note, the second lesion arose from a hybrid neurofibroma/schwannoma. Another case, a 33-year-old male with SMARCB1-related schwannomatosis, had an incidental finding of epithelioid MPNST in a minimally symptomatic small palmar lesion.
    CONCLUSIONS: This case series highlights that MPNSTs, although uncommon, can arise in NF2- and SMARCB1-related schwannomatosis without prior radiation exposure, presenting significant diagnostic challenges due to their similarity to benign schwannomas. The findings underscore the importance of maintaining clinical vigilance and employing individualized management strategies, balancing thorough resection with the preservation of function and patient quality of life.
    Keywords:  SMARCB1; case series; malignant peripheral nerve sheath tumor; neurofibromatosis type 2; oncology; schwannomatosis; vestibular schwannoma
    DOI:  https://doi.org/10.3171/2025.6.JNS25872
  7. J Clin Med. 2025 Nov 01. pii: 7763. [Epub ahead of print]14(21):
    Perineural and Lymphovascular Invasion in Resected Pancreatic Ductal Adenocarcinoma: A High-Risk Subgroup That Could Benefit from Adjuvant Radiotherapy.
    Tufan Gümüş, Aykut Özkılıç, Recep Temel, Deniz Nart, Funda Yılmaz, Bülent Karabulut, Alper Uğuz.
      Background: Perineural invasion (PNI) and lymphovascular invasion (LVI) are adverse prognostic factors in pancreatic ductal adenocarcinoma (PDAC). Their concurrence may warrant intensified adjuvant therapy. This study investigated the prognostic impact of concurrent PNI and LVI and the potential benefit of adjuvant radiotherapy. Methods: A retrospective analysis was conducted in patients who underwent pancreaticoduodenectomy for PDAC (2015-2023). Patients were grouped as PNI only, concurrent PNI and LVI, or neither. Clinicopathological features and survival outcomes were compared. In the concurrent PNI and LVI subgroup, the effect of adjuvant radiotherapy was analyzed according to margin status (R0 vs. R1). Disease-free survival (DFS) and overall survival (OS) were assessed using Kaplan-Meier and Cox models. Results: Eighty-eight patients were included. Recurrence occurred in 83.0%, with locoregional recurrence in 30.1%. Median DFS was 10.5 months and OS was 19.0 months; four patients (4.5%) survived ≥5 years. Concurrent PNI and LVI was observed in 55.7% and independently predicted reduced DFS (HR 3.23; p = 0.002) and OS (HR 2.34; p = 0.02), whereas adjuvant radiotherapy was associated with prolonged DFS (HR 0.48; p = 0.008). Among R0-resected patients with concurrent PNI and LVI, radiotherapy reduced locoregional recurrence (6.3% vs. 46.7%; p = 0.01) and improved median DFS (10.0 vs. 7.0 months; p = 0.04). Conclusions: Patients with concurrent PNI and LVI are a high-risk subgroup of PDAC. Adjuvant radiotherapy after R0 resection may improve DFS and reduce recurrence in these patients.
    Keywords:  adjuvant radiotherapy; lymphovascular invasion; pancreatic ductal adenocarcinoma; perineural invasion; recurrence; survival
    DOI:  https://doi.org/10.3390/jcm14217763
  8. J Neurosurg. 2025 Nov 14. 1-11
    Malignant peripheral nerve sheath tumors in schwannomatosis: systematic review and meta-analysis.
    Ken Porche, Kirsten M Hayford, Chloe Gui, Suganth Suppiah, Robert J Spinner.
       OBJECTIVE: Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive sarcomas commonly associated with neurofibromatosis type 1 (NF1), whose occurrence in schwannomatosis remains poorly understood. This study aimed to characterize MPNSTs in NF type 2 (NF2)- and SMARCB1-related schwannomatosis through a systematic review and meta-analysis of survival outcomes.
    METHODS: A comprehensive search of the PubMed, Embase, Scopus, SEER (Surveillance, Epidemiology, and End Results), and Web of Science databases was conducted from database inception through January 2024. Clinical, radiological, histopathological, and treatment data were extracted. Primary endpoints included overall survival (OS) and progression-free survival (PFS). Predictors of outcomes were analyzed using Kaplan-Meier survival curves and Cox proportional hazards models.
    RESULTS: A total of 39 cases were identified. NF2-related disease accounted for 67% of cases, while 28% were SMARCB1 related. The mean age at MPNST diagnosis was 33 years (range 9-79 years). Pain (41%) and weakness (26%) were the most common presenting symptoms. The mortality rate was 72.9%. No tumors were associated with LZTR1 mutations. Tumor locations varied widely, with involvement of the pelvis, thigh, skull base, forearm/hand, and cranial nerves. Trends suggested improved survival in the absence of S100 loss, gross-total resection, and a known schwannoma precursor. Conversely, having an intracranial or intraspinal lesion or having NF2 in the setting of prior radiation therapy were found to be associated with decreased survival and increased progression. A risk stratification tool predicted OS (HR 28.0, p < 0.0001) and PFS (HR 12.1, p < 0.0001).
    CONCLUSIONS: MPNSTs, although rare in schwannomatosis, can arise even in the absence of prior radiation exposure and may mimic benign schwannomas. A preliminary risk stratification tool may aid in identifying high-risk patients and optimizing treatment approaches, although validation is needed. Given the aggressive nature of MPNSTs and their potential for delayed diagnosis due to their rarity, vigilant monitoring and individualized treatment strategies are crucial. Future research should focus on refining risk prediction models and exploring targeted therapies for schwannomatosis-associated MPNSTs to improve patient outcomes.
    Keywords:  NF2; SMARCB1; malignant peripheral nerve sheath tumor; neurofibromatosis type 2; oncology; schwannomatosis; vestibular schwannoma
    DOI:  https://doi.org/10.3171/2025.6.JNS251508
  9. Sci Rep. 2025 Nov 13. 15(1): 39747
    CLCF1 is associated with perineurial invasion and prognosis in colorectal cancer.
    Wanfang Zhang, Yu Gao, Ni Zhang, Jing Su, Shaojie Li, You Wang, Fuxiang Zhou.
      Perineural invasion (PNI) is implicated in tumor invasion, metastasis, cancer-related pain, and adverse clinical outcomes across various malignancies. Nonetheless, the core genes and molecular mechanisms underlying PNI in colorectal cancer (CRC) remain inadequately understood. The objective of our study was to identify key genes associated with PNI in CRC through bioinformatic analysis. Transcriptomic and clinical data for CRC were obtained from the Cancer Genome Atlas (TCGA) dataset. Using the limma package, we identified 2,446 differentially expressed genes (DEGs) between CRC samples with and without PNI. Additionally, 1,793 immune-related genes (IRGs) were obtained from the ImmPort database. The intersection of differentially expressed immune-related genes (DEIRGs) was subsequently employed for functional enrichment analysis and the development of risk models. A novel prognostic model related to PNI was successfully developed and validated, demonstrating its independent prognostic value in CRC. Cardiotrophin-like cytokine factor 1 (CLCF1) was identified as a key prognostic marker associated with PNI in CRC, with elevated expression observed in tumor samples. CLCF1 was shown to enhance the proliferation, invasion, and migration capabilities of CRC cells, suggesting its potential as a therapeutic target for CRC.
    Keywords:  CLCF1; Colorectal cancer; Perineural invasion; Risk model
    DOI:  https://doi.org/10.1038/s41598-025-15358-1
  10. Medicine (Baltimore). 2025 Nov 14. 104(46): e45539
    Perineural invasion as both a prognostic factor for stage II rectal cancer and an indicator for adjuvant chemotherapy.
    Xiaobo Li, Mingang Yan, Honxi Yu, Houqiong Ju, Taiyuan Li.
      Perineural invasion (PNI) is widely recognized as a significant indicator of tumor aggressiveness and poor prognosis. In patients with stage II colorectal cancer, the presence of PNI may suggest a higher risk of disease recurrence. Therefore, evaluating the potential benefits of adjuvant chemotherapy in this high-risk subgroup is of considerable clinical relevance. Nonetheless, the therapeutic efficacy of such treatment remains a matter of ongoing debate. A retrospective study was conducted on data from patients with stage II rectal cancer (RC) obtained from the Surveillance, Epidemiology, and End Results database (2013-2014) of the National Cancer Institute. Kaplan-Meier survival analysis was performed to estimate survival rates, and group comparisons were conducted using the log-rank test. Univariate and multivariate Cox proportional hazards regression analyses were employed to assess the associations between clinicopathological factors and both overall survival (OS) and cancer-specific survival (CSS). Among the 1372 patients included in the analysis, 144 (10.5%) exhibited PNI. The presence of PNI was significantly associated with carcinoembryonic antigen levels, T stage, and receipt of chemotherapy. Cox proportional hazards regression analysis identified age, carcinoembryonic antigen levels, PNI, radiotherapy, chemotherapy, T stage, and the number of regional lymph nodes examined as independent prognostic factors for both OS and CSS. Additionally, postoperative chemotherapy was associated with improved OS and CSS in patients with stage II RC. PNI is a poor prognostic factor for stage II RC patients. Postoperative chemotherapy improved the prognosis of stage II RC patients with PNI(+).
    Keywords:  PNI; SEER; chemotherapy; rectal cancer
    DOI:  https://doi.org/10.1097/MD.0000000000045539
  11. Ann Surg Oncol. 2025 Nov 11.
    ASO Visual Abstract: Perineural Invasion Worsens Long-Term Outcome of Pancreatic Neuroendocrine Tumors following Surgical Resection.
    Hui Xu, Jing-Jing Hou, Jun-Xi Xiang, Alexandra G Lopez-Aguiar, George Poultsides, Flavio Rocha, Sharon Weber, Ryan Fields, Kamran Idrees, Cliff Cho, Shishir K Maithel, Yi Lv, Xu-Feng Zhang, Timothy M Pawlik.
      
    DOI:  https://doi.org/10.1245/s10434-025-18725-4
  12. BMC Cancer. 2025 Nov 10. 25(1): 1738
    Development and validation of a novel nerve-related prognostic model for gastric cancer based on bulk and single-cell RNA sequencing data.
    Lupeng Qiu, Sheng Yao, Zizhong Yang, Zishan Zhou, Yang Fei, Xinyong Zhu, Feide Liu, Yixin Gong, Shuang Li, Minglu Liu, Xiao Zhao, Shunchang Jiao.
       BACKGROUND: Gastric cancer (GC) is still imposing a severe threat to human health. An increasing number of studies have found that neural activity plays an important role in the tumor microenvironment. However, the clinical implications of nerve-related genes (NRGs) remain largely unexplored.
    METHODS: Matched GC and adjacent normal tissue from 8 patients were collected for single-cell RNA sequencing (scRNA-seq) analysis. Gene expression and patient information were downloaded from TCGA and GEO databases. A total of 441 NRGs were collected from the KEGG database, and LASSO regression analysis was used to construct the nerve-related risk score (NRRS). The survival, immune microenvironment, and mutation analyses were then carried out. Finally, scRNA-seq analysis was used to analyze the distribution of NRGs in GC patients.
    RESULTS: We enrolled 441 NRGs and analyzed the association between NRGs expression and overall survival (OS). Finally, 8 NRGs highly associated with OS were identified to construct the NRRS model. Patients with low NRRS had significantly longer OS compared with high NRRS patients. We then analyzed the distribution of gene mutation landscape, enrichment annotation and immune infiltration in different NRRS subtypes. It was found that high NRRS patients displayed a significantly higher infiltration abundance of immune cell subtypes and immune checkpoint molecules. In addition, scRNA-seq was used to analyze the distribution of NRGs in 8 GC patients. We obtained 55, 052 cells in the scRNA-seq data, and the NRRS signature was significantly higher in GC tissues. EPHB3 and LPAR2 were highly expressed in epithelial cells, while NRP1, GNAI1, and SEMA6A were highly expressed in endothelial cells.
    CONCLUSIONS: Taken together, NRRS could serve as a stable and powerful model for survival prediction, and can help to identify GC patients who may benefit from chemotherapy and immunotherapy.
    Keywords:  Gastric cancer; Immunotherapy; Nerve; Prognosis; Tumor microenvironment
    DOI:  https://doi.org/10.1186/s12885-025-15202-9
  13. Radiol Clin North Am. 2026 Jan;pii: S0033-8389(25)00061-2. [Epub ahead of print]64(1): 107-122
    Imaging Insights into Perineural Tumor Spread.
    Reve Chahine, Hemant Parmar, Mohannad Ibrahim, Francisco Rivas Rodriguez.
      Perineural spread (PNS) is a clinically significant route of tumor extension in head and neck malignancies and is not uncommonly overlooked on imaging. Often clinically occult, PNS may first be suggested by radiologists, and its detection can have significant implications for prognosis and management. This article provides a comprehensive overview of PNS, including relevant cranial nerve anatomy, optimized imaging protocols, and characteristic radiologic features. Multiple illustrative cases are included to improve recognition and highlight the critical role of imaging in the early identification of this often occult disease process.
    Keywords:  Cranial nerves; Head and neck cancer; Imaging; Perineural invasion; Perineural spread; Radiology
    DOI:  https://doi.org/10.1016/j.rcl.2025.05.007
  14. J Clin Exp Neuropsychol. 2025 Nov 14. 1-18
    Improving detection of cancer-related cognitive impairment (CRCI) in non-CNS cancer: current trends and future directions.
    Joost A Agelink van Rentergem, Yuelin Li, Brent J Small.
      Cancer-Related Cognitive Impairment (CRCI) reflects changes in the cognitive performance of individuals diagnosed and treated for cancer. CRCI occurs in a significant percentage of cancer patients and cancer survivors, in both CNS and non-CNS cancer. However, research findings are mixed with regards to the prevalence, the domains affected, and the size of effects for the non-CNS cancer population. This may partly be due to cognitive effects being relatively subtle in this patient population. To improve the sensitivity of studies to detect CRCI, steps are being taken to establish larger samples, but these remain costly. In this narrative review, we describe methodological and statistical developments that may help to improve the sensitivity of our studies in detecting CRCI. We discuss several forms of supervised and unsupervised digital testing based on traditional tests commonly used in neuropsychological assessment, as well as newer paradigms such as Ecological Momentary Assessment and cognitive neuroscience-based tests. With digital tests, new types of behavioral data become available, which allows for more sophisticated data analyses. Additionally, we discuss several statistical approaches to the analysis of cognitive data that can be used to improve sensitivity, such as Item Response Theory, Bayesian mixed-effects models and Machine Learning (see Table 1). We close with several recommendations for the field, regarding the large number of digital test batteries that are becoming available, uncontrolled false positive rates, and inconsistent use of cognitive domains.[Table: see text].
    Keywords:  Neuropsychological tests; cancer-related cognitive impairment; cognitive testing; digital testing; ecological validity; item response theory; machine learning
    DOI:  https://doi.org/10.1080/13803395.2025.2573782
  15. Clin Transl Oncol. 2025 Nov 12.
    Is the risk of brain metastasis and prognosis different in HER2-low breast cancer?
    Yaşar Culha, Beyza Ünlü, Sena Ece Davarcı, Halil Göksel Güzel, Hacer Demir, Banu Öztürk, Meltem Baykara.
       PURPOSE: We aimed to evaluate whether brain metastases, which are one of the most critical factors that have a poor prognostic value and make treatment difficult in breast cancer cases, differ in HER2-low breast cancer and to evaluate the prognosis of HER2-low breast cancer.
    METHOD: This retrospective study included 1134 female patients diagnosed with breast cancer between June 2012 and June 2023 from two tertiary healthcare centers in Türkiye. Molecular groups were examined in six categories according to hormone receptor (HR) and human epidermal growth factor receptor (HER2) status (HR(+) HER2(-), HR(+) HER2-low, HR(+) HER2(+), HR(-) HER2(-), HR(-) HER2-low, and HR(-) HER2(+)).
    RESULTS: The median follow-up period was 56.6 months (IQR 29.9-90.5). We detected HER2-low disease in 155 (13.7%) cases. Among the six molecular groups, the highest brain metastasis rate was observed in the HR(-) HER2-low group (22.2%) (p = 0.001). In the HR(+) HER2-low group, the brain metastasis rate was 3.8%, with no statistically significant difference (p = 0.13). In the multivariate binary logistic regression model, there was a 32.4-fold increase in the risk of brain metastasis for the HR(-) HER2-low group compared to the HR(+) HER2(-) group (OR: 12.4, 95% CI 6.70-156.2, p < 0.001). The analysis reveals no significant increase in risk for the HR(+) HER2-low group (OR: 1.68, CI: 0.42-6.67, p = 0.46). In the Cox's regression model, the highest risk for poor BMFS was found in the HR(-) HER2-low group compared to the HR(+) HER2(-) group, with a 32.8-fold increased risk (HR: 32.82, CI: 7.80-138.3, p < 0.001). In the Cox's regression model, the highest risk for poor DFS was detected in the HR(-) HER2-low group compared to the HR(+) HER2(-) group, with a fourfold increase in risk (HR: 4.05, CI 1.34-12.30, p = 0.013). Shorter BMSS times were observed in the triple-negative and HR(-) HER2-low groups (1.33 and 3.9 months, respectively; p = 0.001).
    CONCLUSION: Our study found that the risk of brain metastasis and disease recurrence increased significantly in the HR(-) HER2-low group, and contrary to some literature data, the risk of brain metastasis in the HR(+) HER2-low group did not differ from the HR(+) HER2(-) group. Both in our study and in many existing studies in the literature, it seems that the HR(+) HER2-low group has a similar prognosis with the HR(+) HER2(-) group, and the HR(-) HER2-low group is in an intermediate form between the HR(-) HER2(+) and HR(-) HER2(-) groups. Recurrence with brain metastasis and general disease recurrence were more common in the HR(-) HER2-low group. The study's retrospective design and the limited number of patients, especially in the HR(-) HER2-low group, along with potential underreporting in 1 + HER2 cases, are notable limitations.
    Keywords:  Brain metastasis; HER2-low breast cancer; Prognosis
    DOI:  https://doi.org/10.1007/s12094-025-04106-6
  16. Cancer Res Commun. 2025 Nov 13.
    Association of neuronal autoantibodies with overall survival in gastric cancer patients.
    Guanghui Liu, Xin Tan, Kaibiao Xu, Jingsi Liu, Qianhui Zheng, Xiaoyun Huang, Suyue Pan, Guoxin Li, Yafang Hu, Hao Liu.
      Neuronal autoantibodies have been identified in immune-mediated encephalitis, and most of which are related to paraneoplastic neurological syndromes (PNS). We detected neuronal autoantibodies in gastric cancer patients without PNS, and illustrated their correlation with clinical prognosis. All serum samples were tested by the mouse brain tissue-based assay (TBA) using immunofluorescence for screening neuronal autoantibodies. Known PNS related neuronal autoantibodies were detected by cell-based assay (CBA). A single-center cohort has been started in Nanfang hospital. T cells status of the tumor microenvironment was assessed. Singel cell sequencing was performed with limited tumor samples. Patients were grouped into TBA positive (n=144) and TBA negative (n=179) groups by the TBA status. Further screening of TBA+ specimens using the CBA method revealed known PNS-related autoantibodies in 13.2% (19/144) of cases. Additionally, TBA positive gastric cancer patients exhibited lower CD8+ T cell infiltration in the tumor tissue. The Survival analysis show that neuronal autoantibodies in patients (TBA positive) were associated with shorter OS (P=0.014). In the multivariate survival analysis, TBA positive was still associated with shortened OS after adjusting the major covariates (HR = 2.28, 95% CI: 1.31-3.97, P = 0.004). Meanwhile, Single-cell sequencing indicates that cell junction assembly and synapse organization may play important roles in biological process. In this cohort study, neuronal autoantibodies were highly prevalent among gastric cancer patients and were associated with shortened OS and features of immunosuppression within the tumor microenvironment, suggesting a candidate for exploring therapeutic relevance, with further mechanistic studies needed to validation.
    DOI:  https://doi.org/10.1158/2767-9764.CRC-25-0495
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