bims-netuvo 2024-11-10 papers

bims-netuvo

Biomed News

on Nerves in tumours of visceral organs

Issue of 2024–11–10
eight papers selected by
Maksym V. Kopanitsa, Charles River Laboratories

Neuroscience in peripheral cancers: tumors hijacking nerves and neuroimmune crosstalk.
Endosomal Trafficking Bypassed by the RAB5B-CD109 Interplay Promotes Axonogenesis in KRAS-Mutant Pancreatic Cancer.
Analysis of Baseline Molecular Factors Associated With the Risk of Central Nervous System Progression Among Alectinib-Treated Patients With ALK-Positive NSCLC.
The benefit and risk of addition of chemotherapy to EGFR tyrosine kinase inhibitors for EGFR-positive non-small cell lung cancer patients with brain metastases: a meta-analysis based on randomized controlled trials.
Adding immune checkpoint inhibitors to chemotherapy confers modest survival benefit in patients with small cell lung cancer and brain metastases: a retrospective analysis.
CT-based radiomics model for predicting perineural invasion status in gastric cancer.
Consensus recommendations for an integrated diagnostic approach to peripheral nerve sheath tumors arising in the setting of Neurofibromatosis type 1 (NF1).
Six at Sixty. Malignant peripheral nerve sheath tumours in NF1: 20-year review of a highly cited paper.

MedComm (2020). 2024 Nov;5(11): e784

Neuroscience in peripheral cancers: tumors hijacking nerves and neuroimmune crosstalk.

Hua-Yang Fan, Xin-Hua Liang, Ya-Ling Tang.

  Cancer neuroscience is an emerging field that investigates the intricate relationship between the nervous system and cancer, gaining increasing recognition for its importance. The central nervous system governs the development of the nervous system and directly affects brain tumors, and the peripheral nervous system (PNS) shapes the tumor microenvironment (TME) of peripheral tumors. Both systems are crucial in cancer initiation and progression, with recent studies revealing a more intricate role of the PNS within the TME. Tumors not only invade nerves but also persuade them through remodeling to further promote malignancy, creating a bidirectional interaction between nerves and cancers. Notably, immune cells also contribute to this communication, forming a triangular relationship that influences protumor inflammation and the effectiveness of immunotherapy. This review delves into the intricate mechanisms connecting the PNS and tumors, focusing on how various immune cell types influence nerve‒tumor interactions, emphasizing the clinical relevance of nerve‒tumor and nerve‒immune dynamics. By deepening our understanding of the interplay between nerves, cancer, and immune cells, this review has the potential to reshape tumor biology insights, inspire innovative therapies, and improve clinical outcomes for cancer patients.

Keywords:  cancer neuroscience; cancer therapy; neuroimmune crosstalk; peripheral nervous system; tumor microenvironment; tumor‒nerve interactions

DOI:  https://doi.org/10.1002/mco2.784
Adv Sci (Weinh). 2024 Nov 03. e2405092

Endosomal Trafficking Bypassed by the RAB5B-CD109 Interplay Promotes Axonogenesis in KRAS-Mutant Pancreatic Cancer.

Dingwen Zhang, Yuming Luo, Yan Lin, Zhou Fang, Hanhao Zheng, Mingjie An, Qingyu Xie, Zhuo Wu, Chao Yu, Jiabin Yang, Min Yu, Changhao Chen, Rufu Chen.

  Perineural invasion (PNI) represents a unique biological feature associated with poor prognosis in pancreatic ductal adenocarcinoma (PDAC), especially in the presence of KRAS mutations. Extracellular vesicle (EV)-packaged circular RNAs (circRNAs) function as essential mediators of tumor microenvironment communication, triggering PDAC cell invasion and distant metastasis. However, the regulatory mechanisms of EV-packaged circRNAs in the PNI of KRAS-mutant PDAC have not yet been elucidated. Herein, a KRASG12D mutation-responsive EV-packaged circRNA, circPNIT, which positively correlated with PNI in PDAC patients is identified. Functionally, KRASG12D PDAC-derived EV-packaged circPNIT promoted axonogenesis and PNI both in vitro and in vivo. Mechanistically, the circPNIT-mediated Rab5B-CD109 interplay bypassed traditional endosomal trafficking to anchor Rab5B to the lipid rafts of multivesicular bodies and packaged circPNIT into CD109+ EVs. Subsequently, CD109+ EVs delivered circPNIT to neurons by binding to TRPV1 and facilitating DSCAML1 transcription-induced axonogenesis, which in turn enhanced the PNI by activating the GFRα1/RET pathway. Importantly, circPNIT-loaded CD109+ EVs are established to dramatically promote PNI in a KRASG12D/+ Trp53R172H/+ Pdx-1-Cre mouse model. Collectively, the findings highlight the mechanism underlying how EV-packaged circRNAs mediate the PNI of KRAS-mutant PDAC cells through the Rab5B endosomal bypass, identifying circPNIT as an effective target for the treatment of neuro-metastatic PDAC.

Keywords:  KRAS mutation; circular RNA; engineered extracellular vesicle; pancreatic cancer; perineural invasion

DOI:  https://doi.org/10.1002/advs.202405092
JTO Clin Res Rep. 2024 Dec;5(12): 100729

Analysis of Baseline Molecular Factors Associated With the Risk of Central Nervous System Progression Among Alectinib-Treated Patients With ALK-Positive NSCLC.

Lianxi Song, Huan Yan, Qinqin Xu, Chunhua Zhou, Juan Liang, Shaoding Lin, Ruiguang Zhang, Juan Yu, Yang Xia, Nong Yang, Liang Zeng, Yongchang Zhang.

   Introduction: Despite receiving alectinib therapy, patients with ALK-positive NSCLC remain at risk of central nervous system (CNS) progression. Our retrospective study aimed to identify baseline clinical and molecular factors associated with the risk of CNS progression in this patient subset.
Methods: We analyzed the clinical, molecular, and imaging data of 318 patients with ALK-positive advanced NSCLC who received alectinib as first-line (1L-alectinib) or second-line (2L-alectinib) therapy at baseline (1L, n = 183; 2L, n = 135) and at disease progression (1L, n = 80; 2L, n = 76).
Results: The incidence rates of CNS progression were 23.7% after 1L-alectinib treatment and 31.6% after 2L-alectinib treatment. Compared with patients who received 1L-alectinib, CNS progression was similar in patients who received 2L-alectinib (p > 0.05). Oligoprogression was detected in 55.0% (44 of 80) of patients who progressed after first-line alectinib, with the remaining 45.0% (36 of 80) having nonoligoprogression. Univariate and multivariate analyses and stepwise regression analyses consistently identified a higher likelihood of CNS progression among (1) patients who received 2L-alectinib than 1L-alectinib, (2) patients with non-3a/b variant ALK fusion than those with echinoderm microtubule-associated protein-like 4-ALK variant 3a/b, and (3) patients with programmed death ligand 1 (PD-L1) tumor proportion score (TPS) of 50% or higher than PD-L1 TPS of less than 50%.
Conclusions: Our study provided real-world evidence that patients who harbored PD-L1 TPS of 50% or higher were more likely to experience CNS progression during alectinib therapy. The association between CNS progression and breakpoint variants warrants further investigation. Our findings suggest that close monitoring and prompt intervention are crucial in prolonging the quality of life of this patient subset.

Keywords:  ALK; Alectinib; Biomarker; CNS progression; Non–small cell lung cancer

DOI:  https://doi.org/10.1016/j.jtocrr.2024.100729
Front Oncol. 2024 ;14 1448336

The benefit and risk of addition of chemotherapy to EGFR tyrosine kinase inhibitors for EGFR-positive non-small cell lung cancer patients with brain metastases: a meta-analysis based on randomized controlled trials.

Zhigang Chen, Xiang Fu, Lingping Zhu, Xiurong Wen, Shihao Zhang.

   Background: Combining epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) with chemotherapy (ETC) offers more advantages for patients with EGFR-positive non-small cell lung cancer (NSCLC) than using EGFR TKIs alone (ET). However, whether this conclusion applies to patients with brain metastases (BM) remains controversial. This meta-analysis was performed to evaluate the benefits and risks of the two groups.
Methods: Six databases were systematically searched for relevant literatures comparing ETC versus ET in treating EGFR-positive NSCLC patients with BM. The primary outcome assessed was overall survival (OS), while secondary outcomes included progression-free survival (PFS), and central nervous system (CNS)-PFS, responses, progression status and safety.
Results: Seven studies based on five randomized clinical trials with 550 patients were included. The ETC group exhibited better OS (hazard ratio [HR]: 0.64 [0.48, 0.87]), PFS (HR: 0.42 [0.34, 0.52]), and CNS-PFS (HR: 0.42 [0.31, 0.57]). The benefits in survival for OS, PFS, and CNS-PFS were validated in nearly all subgroups. Meanwhile, the overall objective response rate (ORR) (risk ratio [RR]: 1.25 [1.02, 1.52]) and CNS-ORR (RR: 1.19 [0.93, 1.51]) also tended to favor the ETC group. However, the addition of chemotherapy also brought about more grade 3-5/serious adverse events (AEs). The top five grade 3-5 AEs in the ETC group were alanine aminotransferase increase (11.25%), neutropenia (7.5%), nausea (7.5%), anorexia (5%), and diarrhea (5%).
Conclusions: ETC appears to be better than ET in treating EGFR-positive NSCLC patients with BM, with better OS, PFS, CNS-PFS, and responses. However, its poorer safety profile also needs to be taken into consideration.
Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024551073.

Keywords:  EGFR; brain metastases; chemotherapy; meta-analysis; non-small cell lung cancer; tyrosine kinase inhibitors

DOI:  https://doi.org/10.3389/fonc.2024.1448336
Transl Lung Cancer Res. 2024 Oct 31. 13(10): 2479-2490

Adding immune checkpoint inhibitors to chemotherapy confers modest survival benefit in patients with small cell lung cancer and brain metastases: a retrospective analysis.

Baishen Zhang, Jing Chen, Hui Yu, Meichen Li, Likun Chen.

   Background: Brain metastases (BM) are highly prevalent and associated with a poor prognosis in patients with small cell lung cancer (SCLC). However, the evidence regarding the efficacy of immune checkpoint inhibitors (ICIs) in combination with chemotherapy for patients with SCLC and BM remains limited. Therefore, the objective of this study is to evaluate whether the addition of ICIs confers survival benefits for patients with SCLC and BM.
Methods: This retrospective study enrolled patients with SCLC and BM at the Sun Yat-sen University Cancer Center between January 2018 and December 2022. Clinical characteristics were extracted from medical records. Depending on whether ICIs were added to the first-line treatment, the patients were categorized into the chemotherapy group and the chemoimmunotherapy group. The efficacy of these two treatment approaches was analyzed and compared.
Results: A total of 165 patients were enrolled, with 85 in the chemotherapy group and 80 in the chemoimmunotherapy group. The chemoimmunotherapy group showed a tendency towards prolonged intracranial [6.6 vs. 5.9 months, hazard ratio (HR) =0.77; P=0.14] and extracranial (6.9 vs. 6.5 months, HR =0.73; P=0.12) progression-free survival (PFS) and overall survival (OS) (15.6 vs. 14.5 months, HR =0.98; P=0.93) compared to the chemotherapy group. Cox regression analysis identified liver metastases and local treatment for BM as independent prognostic factors for OS in patients. Furthermore, the chemotherapy group and the chemoimmunotherapy group demonstrated similar patterns of initial disease progression.
Conclusions: Adding ICIs to chemotherapy confers modest survival benefits in patients with SCLC and BM.

Keywords:  Small cell lung cancer (SCLC); brain metastasis; immune checkpoint inhibitors (ICIs); intracranial and extracranial efficacy

DOI:  https://doi.org/10.21037/tlcr-24-335
Abdom Radiol (NY). 2024 Nov 06.

CT-based radiomics model for predicting perineural invasion status in gastric cancer.

Sheng Jiang, Wentao Xie, Wenjun Pan, Zinian Jiang, Fangjie Xin, Xiaoming Zhou, Zhenying Xu, Maoshen Zhang, Yun Lu, Dongsheng Wang.

   PURPOSE: Perineural invasion (PNI) is an independent risk factor for poor prognosis in gastric cancer (GC) patients. This study aimed to develop and validate predictive models based on CT imaging and clinical features to predict PNI status in GC patients.
METHODS: This retrospective study included 291 GC patients (229 in the training cohort and 62 in the validation cohort) who underwent gastrectomy between January 2020 and August 2022. The clinical data and preoperative abdominal contrast-enhanced computed tomography (CECT) images were collected. Radiomics features were extracted from the venous phase of CECT images. The intraclass correlation coefficient (ICC), Pearson correlation coefficient, and t-test were applied for radiomics feature selection. The random forest algorithm was used to construct a radiomics signature and calculate the radiomics feature score (Rad-score). A hybrid model was built by aggregating the Rad-score and clinical predictors. The area under the receiver operating characteristic curve (ROC) and decision curve analysis (DCA) were used to evaluate the prediction performance of the radiomics, clinical, and hybrid models.
RESULTS: A total of 994 radiomics features were extracted from the venous phase images of each patient. Finally, 5 radiomics features were selected and used to construct a radiomics signature. The hybrid model demonstrated strong predictive ability for PNI, with AUCs of 0.833 (95% CI: 0.779-0.887) and 0.806 (95% CI: 0.628-0.983) in the training and validation cohorts, respectively. The DCA showed that the hybrid model had good clinical utility.
CONCLUSION: We established three models, and the hybrid model that combined the Rad-score and clinical predictors had a high potential for predicting PNI in GC patients.

Keywords:  CT; Computer assisted; Gastric cancer; Image processing; Perineural invasion; Random forest

DOI:  https://doi.org/10.1007/s00261-024-04673-2
Neuro Oncol. 2024 Nov 06. pii: noae235. [Epub ahead of print]

Consensus recommendations for an integrated diagnostic approach to peripheral nerve sheath tumors arising in the setting of Neurofibromatosis type 1 (NF1).

Symposium on Atypical Neurofibroma: State of the Science Members

  Consensus recommendation published in 2017 histologically defining atypical neurofibromatous neoplasm of uncertain biologic potential (ANNUBP) and malignant peripheral nerve sheath tumor (MPNST) were codified in the 2021 WHO Classification of Tumors of the Central Nervous System and the 2022 WHO Classification of Tumors of Soft Tissue and Bone. However, given the shift in diagnostic pathology toward the use of integrated histopathologic and genomic approaches, the incorporation of additional molecular strata in the classification of Neurofibromatosis Type 1 (NF1)-associated peripheral nerve sheath tumors should be formalized to aid in accurate diagnosis and early identification of malignant transformation to enable appropriate intervention for affected patients. To this end, we assembled a multi-institutional expert pathology working group as part of a "Symposium on Atypical Neurofibroma: State of the Science". Herein, we provide a suggested framework for adequate interventional radiology and surgical sampling, and recommend molecular profiling for clinically or radiologically worrisome non-cutaneous lesions in patients with NF1 to identify diagnostically-relevant molecular features, including CDKN2A/B inactivation for ANNUBP, as well as SUZ12, EED, or TP53 inactivating mutations, or significant aneuploidy for MPNST. We also propose renaming "low-grade MPNST" to "ANNUBP with increased proliferation" to avoid the use of the "malignant" term in this group of tumors with persistent unknown biologic potential. This refined integrated diagnostic approach for NF1-associated peripheral nerve sheath tumors should continue to evolve in concert with our understanding of these neoplasms.

Keywords:  consensus; guidelines; molecular neuropathology; nerve sheath tumor; neurofibromatosis type 1

DOI:  https://doi.org/10.1093/neuonc/noae235
J Med Genet. 2024 Nov 04. pii: jmg-2024-110396. [Epub ahead of print]

Six at Sixty. Malignant peripheral nerve sheath tumours in NF1: 20-year review of a highly cited paper.

D Gareth Evans, Emma Burkitt-Wright, John Ealing, Grace Vassello, Judith Eelloo, Alexander Lee.



Keywords:  Genomics

DOI:  https://doi.org/10.1136/jmg-2024-110396