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JAMA Dermatology Dec 2023Perineural invasion (PNI) is an adverse risk feature in cutaneous squamous cell carcinoma (CSCC) that affects patient prognosis and disease management. However, research...
IMPORTANCE
Perineural invasion (PNI) is an adverse risk feature in cutaneous squamous cell carcinoma (CSCC) that affects patient prognosis and disease management. However, research comparing different PNI patterns on patient outcomes is limited.
OBJECTIVE
To compare 4 assessments of PNI in CSCC, their associations with poor outcomes, and implications for their inclusion in the Brigham and Women's Hospital (BWH) staging system.
DESIGN, SETTING, AND PARTICIPANTS
This retrospective cohort study was performed at a single tertiary care institution and compared 4 PNI assessments: nerve caliber, number of involved nerves per section, PNI maximal depth, and PNI location with respect to tumor. Patients with primary, localized, invasive CSCC with PNI diagnosed between January 1, 2000, and December 31, 2017, were identified via an electronic in-house database. Available pathology slides were secondarily reviewed by study authors. Relevant patient and tumor characteristics and outcomes were abstracted from the medical record. Data analysis was performed between September 6 and October 20, 2022.
MAIN OUTCOMES AND MEASURES
Risks of recurrence, disease-specific death, and a composite end point (any poor outcome) were calculated via multivariable stepwise Fine and Gray competing-risks regression. Considered revisions to the BWH staging system were assessed via receiver operating characteristic curves and test characteristics.
RESULTS
This study included 140 patients with CSCC, with a mean (SD) age of 75.1 (11.2) years. More than half of the patients were men (93 [66.4%]), and most identified as White (132 [94.3%]). Of the 4 PNI assessments studied, only involvement of multiple nerves was associated with poor outcomes. Perineural invasion of 5 or more distinct nerves (extensive PNI [ePNI]) was independently associated with local recurrence (subhazard ratio [SHR], 13.83 [95% CI, 3.50-54.62]; P < .001), disease-specific death (SHR, 6.20 [95% CI, 1.59-24.21]; P = .009), and any poor outcome (SHR, 10.21 [95% CI, 2.88-36.15]; P < .001). A revised BWH staging system with substitution of ePNI for large-caliber PNI resulted in improved area under the curve and test characteristics compared with current BWH staging criteria that use nerve caliber as the measure of PNI.
CONCLUSIONS AND RELEVANCE
The findings of this cohort study suggest that ePNI is the best prognostic measure of PNI. Because ePNI obviated the need for a micrometer and had superior prognostic capacity to nerve caliber in this cohort, ePNI should be considered for inclusion in CSCC tumor staging. Inclusion of ePNI as a high-risk factor in CSCC staging systems may optimize patient selection for primary treatment and adjuvant interventions.
Topics: Male; Humans; Female; Aged; Carcinoma, Squamous Cell; Cohort Studies; Retrospective Studies; Skin Neoplasms; Prognosis; Neoplasm Staging; Neoplasm Invasiveness
PubMed: 37851425
DOI: 10.1001/jamadermatol.2023.3703 -
Head & Neck Sep 2023Perineural invasion (PNI) in head and neck squamous cell carcinoma (HNSCC) portends poor prognosis. Extent of treatment of nerve pathways with varying degrees of PNI and...
BACKGROUND
Perineural invasion (PNI) in head and neck squamous cell carcinoma (HNSCC) portends poor prognosis. Extent of treatment of nerve pathways with varying degrees of PNI and patterns of failure following elective neural radiotherapy (RT) remain unclear.
METHODS
Retrospective review of HNSCC patients with high-risk (clinical/gross, large-nerve, extensive) or low-risk (microscopic/focal) PNI who underwent curative-intent treatment from 2010 to 2021.
RESULTS
Forty-four patients (mean follow-up 22 months; 59% high-risk, 41% low-risk PNI) were included. Recurrence following definitive treatment occurred in 31% high-risk and 17% low-risk PNI patients. Among high-risk patients, 69% underwent surgery with post-operative RT and 46% underwent elective neural RT. Local control (83% low-risk vs. 75% high-risk), disease-free, and overall survival did not differ between groups.
CONCLUSIONS
High local control rates were achieved in high-risk PNI patients treated with adjuvant or primary RT, including treatment of both involved and uninvolved, communicating cranial nerves, with few failures in electively treated regions.
Topics: Humans; Squamous Cell Carcinoma of Head and Neck; Carcinoma, Squamous Cell; Skin Neoplasms; Cranial Nerves; Retrospective Studies; Head and Neck Neoplasms; Neoplasm Invasiveness; Prognosis
PubMed: 37448346
DOI: 10.1002/hed.27458 -
Cancer Letters Apr 2024Pancreatic ductal adenocarcinoma (PDAC), characterized by heightened neural density, presents a challenging prognosis primarily due to perineural invasion. Recognized... (Review)
Review
Pancreatic ductal adenocarcinoma (PDAC), characterized by heightened neural density, presents a challenging prognosis primarily due to perineural invasion. Recognized for their crucial roles in neural support and myelination, Schwann cells (SCs) significantly influence the process of tumorigenesis. This review succinctly outlines the interplay between PDAC and neural systems, positioning SCs as a nexus in the tumor-neural interface. Subsequently, it delves into the cellular origin and influencers of SCs within the pancreatic tumor microenvironment, emphasizing their multifaceted roles in tumor initiation, progression, and modulation of the neural and immune microenvironment. The discussion encompasses potential therapeutic interventions targeting SCs. Lastly, the review underscores pressing issues, advocating for sustained exploration into the diverse contributions of SCs within the intricate landscape of PDAC, with the aim of enhancing our understanding of their involvement in this complex malignancy.
Topics: Humans; Pancreatic Neoplasms; Carcinoma, Pancreatic Ductal; Pancreas; Schwann Cells; Carcinogenesis; Cell Transformation, Neoplastic; Tumor Microenvironment
PubMed: 38367898
DOI: 10.1016/j.canlet.2024.216689 -
Current Cancer Drug Targets 2024Tropomyosin receptor kinase (TRK) A, TRKA, is a specific binding receptor of nerve growth factor (NGF), which plays an essential role in the occurrence and progression... (Review)
Review
Tropomyosin receptor kinase (TRK) A, TRKA, is a specific binding receptor of nerve growth factor (NGF), which plays an essential role in the occurrence and progression of human cancers. TRKA overexpression has been proven to be a powerful carcinogenic driver and has been verified in many tumors. The TRKA receptor kinase domain is over-activated in an NGF-dependent manner, accompanied by activation of downstream signal pathways, such as RAS-MAPK, PI3K-AKT, JAK2-STAT3 pathway, PLC γ pathway, and Hippo pathway, which participate in tumor cell proliferation, invasion, epithelial-mesenchymal transition (EMT), perineural invasion (PNI), drug resistance, and cancer pain. In addition, chimeric oncogenes produced by the fusion of NTRK1 and other genes are also the direct cause of tumorigenesis and cancer development. The newly developed TRK inhibitors can improve symptoms and tumor regression in cancer patients with overexpression of TRKA or NTRK1 fusion gene. With the emergence of drug resistance, next generation of TRK inhibitors can still maintain strong clinical efficacy in the case of TRK kinase domain mutations, and these inhibitors are in clinical trials. This review summarizes the characteristics and research progress of TRKA, focusing on the regulatory role of the TRKA signal pathway in different tumors. In addition, we have summarized the clinical significance of TRKA and the TRK inhibitors. This review may provide a new reference for the study of the mechanism of TRKA in different tumors, and also provide a new perspective for the in-depth understanding of the role of TRKA as a biomarker and therapeutic target in human cancer.
Topics: Humans; Nerve Growth Factor; Phosphatidylinositol 3-Kinases; Signal Transduction; Receptor, trkA; Neoplasms; Carcinogenesis
PubMed: 37670705
DOI: 10.2174/1568009623666230904150957 -
Research Square Jul 2023While the nervous system has reciprocal interactions with both cancer and the immune system, little is known about the potential role of tumor associated nerves (TANs)...
While the nervous system has reciprocal interactions with both cancer and the immune system, little is known about the potential role of tumor associated nerves (TANs) in modulating anti-tumoral immunity. Moreover, while peri-neural invasion is a well establish poor prognostic factor across cancer types, the mechanisms driving this clinical effect remain unknown. Here, we provide clinical and mechniastic association between TANs damage and resistance to anti-PD-1 therapy. Using electron microscopy, electrical conduction studies, and tumor samples of cutaneous squamous cell carcinoma (cSCC) patients, we showed that cancer cells can destroy myelin sheath and induce TANs degeneration. Multi-omics and spatial analyses of tumor samples from cSCC patients who underwent neoadjuvant anti-PD-1 therapy demonstrated that anti-PD-1 non-responders had higher rates of peri-neural invasion, TANs damage and degeneration compared to responders, both at baseline and following neoadjuvant treatment. Tumors from non-responders were also characterized by a sustained signaling of interferon type I (IFN-I) - known to both propagate nerve degeneration and to dampen anti-tumoral immunity. Peri-neural niches of non-responders were characterized by higher immune activity compared to responders, including immune-suppressive activity of M2 macrophages, and T regulatory cells. This tumor promoting inflammation expanded to the rest of the tumor microenvironment in non-responders. Anti-PD-1 efficacy was dampened by inducing nerve damage prior to treatment administration in a murine model. In contrast, anti-PD-1 efficacy was enhanced by denervation and by interleukin-6 blockade. These findings suggested a potential novel anti-PD-1 resistance drived by TANs damage and inflammation. This resistance mechanism is targetable and may have therapeutic implications in other neurotropic cancers with poor response to anti-PD-1 therapy such as pancreatic, prostate, and breast cancers.
PubMed: 37503252
DOI: 10.21203/rs.3.rs-3161761/v1 -
Annals of Surgery Oct 2023Defining the role of adjuvant therapy in duodenal adenocarcinoma (DAC) and intestinal subtype ampullary carcinoma (iAC).
OBJECTIVE
Defining the role of adjuvant therapy in duodenal adenocarcinoma (DAC) and intestinal subtype ampullary carcinoma (iAC).
SUMMARY BACKGROUND DATA
DAC and iAC share a similar histological differentiation but the benefit of adjuvant therapy remains unclear.
METHODS
Patients undergoing curative-intent surgical resection for DAC and iAC between 2010 and 2021 at five high-volume centers were included. Patient baseline, perioperative and long-term oncological outcomes were evaluated. Statistical testing was performed with SPSS 25 (IBM).
RESULTS
A total of 136 patients with DAC and 171 with iAC were identified. Patients with DAC had more advanced tumors than those with iAC. Median overall survival (OS) in DAC patients was 101 months versus 155 months for iAC patients (P=0.098). DAC had a higher rate of local (14.1% vs. 1.2%, P<0.001) and systemic recurrence (30.4% vs. 3.5%, P<0.001). Adjuvant therapy failed to improve overall survival in all patients with DAC and iAC. For DAC, patients with perineural invasion, but not other negative prognostic factors had improved OS rates with adjuvant therapy (72 m vs. 44 m, P=0.044). IAC patients with N+ (190 m vs. 57 m, P=0.003), T3-4 (177 m vs. 59 m, P=0.050) and perineural invasion (150 m vs. 59 m, P=0.019) had improved OS rates with adjuvant therapy.
CONCLUSION
While adjuvant therapy fails to improve OS in all patients with DAC and iAC in the current study, it improved overall survival in DAC patients with perineural invasion and in iAC patients with T3-4 tumors, positive lymph nodes, and perineural invasion.
PubMed: 37830246
DOI: 10.1097/SLA.0000000000006129 -
Cancer Medicine Oct 2023To investigate the clinicopathological characteristics and prognostic factors of early-stage breast cancer (EBC) with human epidermal growth factor receptor 2 (HER2)-low...
Analysis of clinicopathological characteristics and prognostic factors of early-stage human epidermal growth factor receptor 2 (HER2)-low breast cancer: Compared with HER2-0 breast cancer.
PURPOSE
To investigate the clinicopathological characteristics and prognostic factors of early-stage breast cancer (EBC) with human epidermal growth factor receptor 2 (HER2)-low expression.
METHODS
The clinicopathological data and follow-up information of EBC patients with HER2-low and HER2-0 expression treated at the Breast Disease Center of Peking University First Hospital from January 2014 to December 2017 were analyzed. The prognosis between HER2-low and HER2-0 expression groups and with different hormone receptor (HR) expression were compared by statistics. Meanwhile, the expression of Ki67, androgen receptor (AR), TOPIIa, P53, PTEN, and CK5/6 were also analyzed with the HER2-low expression and prognosis.
RESULTS
Retrospectively analyzed 1253 cases of EBC, including 583 (46.5%) cases of HER2-low breast cancer (BC) and 366 (29.2%) HER2-0 BC cases. Among the HER2-low BC patients, 487 (83.5%) were HR-positive, while 96 (16.5%) were HR-negative. Among the HER2-0 BC patients, 265 (72.4%) were HR-positive, while 101 (27.6%) were HR-negative. Median follow-up time was 53 months. The 5-year disease-free survival of HER2-low BC patients was 90.2% (95% confidence interval [CI]: 87.2-93.1), and the 5-year overall survival was 95.4% (95% CI: 93.3-97.6). Cox regression analysis showed that T stage, lymphovascular invasion, and/or perineural invasion were prognostic factors of HER2-low BC patients. However, the 5-year disease-free survival and overall survival of patients in the HER2-low and HER2-0 groups were not significantly different in all patients, but a tendency of better prognosis in HER2-low group was seen in HR-negative tumors.
CONCLUSION
HER2-low EBC patients accounted for 46.5% of the patient population. T stage, lymphovascular invasion, and/or perineural invasion were factors affecting the prognosis of BC patients with low HER2 expression. No significant difference in prognosis was noted between HER2-low and HER2-0 EBC patients. But in HR-negative tumors, a tendency of better prognosis was seen in HER2-low versus HER2-0.
Topics: Female; Humans; Biomarkers, Tumor; Breast Neoplasms; Prognosis; Receptor, ErbB-2; Retrospective Studies
PubMed: 37772432
DOI: 10.1002/cam4.6571 -
Indian Journal of Otolaryngology and... Sep 2023Ganglioneuromas (GNs) are slow-growing, benign tumors arising from Schwann cells, gangliocytes, and neuronal tissues. We report a rare intraparotid ganglioneuroma in a...
Ganglioneuromas (GNs) are slow-growing, benign tumors arising from Schwann cells, gangliocytes, and neuronal tissues. We report a rare intraparotid ganglioneuroma in a 42-year-old female presented with a parotid mass. The onset of the lesion dated back to 2021, but the growth was remarkable only in November 2022. The FNA suggested a plexiform neurofibroma. The post-surgical microscopic examination of the excised lesion revealed neoplastic large, rounded cells with abundant, finely granular eosinophilic cytoplasm and a large, eccentric nucleus with a prominent nucleolus as well as fasciculated, with an elongated cytoplasm with fine fibrillar extensions. No mitosis or tumor necrosis was observed. The periphery of the tumor showed perineural entrapment. The immunohistochemical staining for S100 protein, synaptophysin, and chromogranin A were positive. However, the neoplastic cells showed no immunoreactivity for cytokeratin (CK5/6, CK7, AE1/AE3), epithelial membrane antigen, HMB45, Melan A, CD30, CD117 and p40. The case was signed out as mature intraparotid ganglioneuroma. The treatment of choice was surgical resection without adjuvant radiotherapy. No recurrence or post-surgical complications were hitherto reported. To the best of our knowledge, this is the first reported case of intraparotid ganglioneuroma. Caution should be taken not to diagnose this benign neoplasm as a metastasis (e.g. metastatic neuroblastoma) or to request unnecessary overtreatment (e.g., postoperative chemotherapy and radiotherapy).
PubMed: 37636636
DOI: 10.1007/s12070-023-03800-7 -
Journal of Ultrasonography Oct 2023Ultrasound visualization affords proceduralists versatile and accurate guidance for a variety of percutaneous, minimally invasive procedures in the musculoskeletal...
Ultrasound visualization affords proceduralists versatile and accurate guidance for a variety of percutaneous, minimally invasive procedures in the musculoskeletal system including joint (intra-articular) injections or aspirations, intra-bursal injections, peritendinous, and perineural injections. A variety of percutaneous procedures are traditionally performed blindly, but may be more easily or more accurately performed with the real-time assistance of ultrasound guidance. Other procedures are only possible utilizing image-guidance, due to the required precision of the injection because of delicate local anatomy or depth of the injection; ultrasound is a safe, portable, and widespread modality that can be used to assist the proceduralist in localizing the needle tip in such cases, to ensure safe and accurate delivery of the medication, most frequently a solution of steroid and anesthetic. This review aims to provide a foundational approach to ultrasound-guided procedures in the musculoskeletal system, offering tips and tricks that can be employed in many different procedures including intra-articular, juxta-articular, and perineural injections for a multitude of clinical scenarios. Technical considerations regarding ultrasound transducer selection, sonographic technique, as well as common indications, contraindications, and complications of these procedures, are presented. Additionally, a variety of pharmacologic considerations for proceduralists contemplating ultrasound-guided injections are discussed.
PubMed: 38020507
DOI: 10.15557/jou.2023.0039 -
Journal of Oral and Maxillofacial... May 2024Head and neck osteosarcoma (HNOS) is the most common bone malignancy in the head and neck region, accounting for 10% of all osteosarcoma cases. Perineural invasion (PNI)...
BACKGROUND
Head and neck osteosarcoma (HNOS) is the most common bone malignancy in the head and neck region, accounting for 10% of all osteosarcoma cases. Perineural invasion (PNI) is a notable indication of aggressive tumor behavior, which includes the phenomenon of tumor cells invading any of the 3 layers of the nerve sheath or tumor cells gathering, encircling one-third of the nerve circumference, and infiltrating and metastasizing along the nerve. PNI has been reported in various malignant tumors and is considered to be linked to poor prognosis.
PURPOSE
The study's purpose is to measure the association between PNI and survival outcomes in patients with HNOS.
STUDY DESIGN, SETTING, SAMPLE
This retrospective cohort study focused on HNOS patients who underwent surgery at the Department of Oral and Maxillofacial Head and Neck Oncology, Shanghai Ninth People's Hospital School of Medicine, Shanghai Jiao Tong University, from January 1, 2019 to December 31, 2021. Patients who did not undergo complete surgical resection of the tumor, did not receive a conventional osteosarcoma diagnosis, and had positive surgical margins were eliminated.
PREDICTOR VARIABLE
The predictor variable is PNI status. The pathological section of the tumor was consistent with any of the PNI features, which was considered PNI-positive.
MAIN OUTCOME VARIABLE(S)
The primary outcome variables were 3-year disease-free survival (DFS) and 3-year overall survival. Secondary outcomes were 3-year tumor local recurrence and 3-year metastasis (MT).
COVARIATES
Covariates were categorized into the following categories: demographic variables (age, sex), clinical variables (tumor region, primary tumor), and treatment variables (chemotherapy, radiotherapy).
ANALYSES
Analytic statistical methods were used for the data analysis. Pearson χ or Fisher's exact test was used to describe the baseline data. Kaplan-Meier is used to calculate survival rates. The Cox regression model was adapted for univariate and multivariate analysis. A P value less than .05 indicated statistical significance.
RESULTS
The study sample comprised 70 patients; 33 (47.1%) were male, and the mean age was 42.2 (standard deviation: 16.7) years. There were 15 (21.4%) cases of PNI. The 3-year DSF rate and OS rate were 67.3% and 82.0%, respectively. PNI-positive resulted in higher risk for MT (P < .01, hazard ratio: 5.95, 95% confidence interval: 1.62-21.86) and negative impact on DFS (P < .01, hazard ratio: 6.35, 95% confidence interval: 2.11-19.17) for HNOS patients.
CONCLUSION AND RELEVANCE
Positive PNI status was associated with decreased DFS and increased risk of MT.
PubMed: 38797510
DOI: 10.1016/j.joms.2024.05.001