bims-netuvo Biomed News
on Nerves in tumours of visceral organs
Issue of 2024–12–01
eleven papers selected by
Maksym V. Kopanitsa, Charles River Laboratories
  1. Targeting CNS Metastases in Non-Small Cell Lung Cancer With Evolving Approaches Using Molecular Markers: A Review.
  2. Perineural invasion for risk stratification in cutaneous squamous cell carcinoma: a scoping review.
  3. Survival and Treatment Outcomes in Gastric Cancer Patients with Brain Metastases: A Systematic Review and Meta-Analysis.
  4. NK1 receptor blockade disrupts microtumor growth and aggregation in a three-dimensional murine breast cancer model.
  5. Development of a nomogram for predicting cancer pain in lung cancer patients: An observational study.
  6. Neurostimulation for the Treatment of Cancer-Induced Pain: A Scoping Review.
  7. β-blockers and statins: exploring the potential off-label applications in breast, colorectal, prostate, and lung cancers.
  8. Perioperative Observations and Outcome in Surgical Treatment of Malignant Peripheral Nerve Sheath Tumors.
  9. Obturator nerve schwannoma: a case report and review of the robotic literature.
  10. Six year natural progression of a clinically monitored retroperitoneal schwannoma: A case report.
  11. Fatal abdominal hemorrhage following surgery to remove a retroperitoneal MPNST associated with NF1: A case report.
  1. JAMA Oncol. 2024 Nov 27.
    Targeting CNS Metastases in Non-Small Cell Lung Cancer With Evolving Approaches Using Molecular Markers: A Review.
    Jyoti Malhotra, Isa Mambetsariev, Gregory Gilmore, Jeremy Fricke, Arin Nam, Natalie Gallego, Bihong T Chen, Mike Chen, Arya Amini, Rimas V Lukas, Ravi Salgia.
       Importance: Central nervous system (CNS) metastases presenting as either brain parenchymal metastases or leptomeningeal metastases are diagnosed in up to 50% of patients with advanced non-small cell lung cancer during their disease course. While historically associated with a poor prognosis due to limited treatment options, the availability of an increasing number of targeted therapies with good CNS penetration has significantly improved clinical outcomes for these patients. This has occurred in parallel with a more nuanced understanding of prognostic factors.
    Observations: Multiple clinical trials have reported that disease control can be observed with targeted therapies with adequate CNS penetration, particularly for patients with molecular alterations in EGFR, ALK, ROS1, and RET. For these tumors, systemic targeted therapy may be used first for the management of CNS metastases, prior to considering radiation therapy (RT). At the time of isolated progression in the CNS, RT may be considered for the progressing lesions with continuation of the same systemic therapy. For other molecular alterations as well as for patients treated with checkpoint inhibitors, data are not yet clear if systemic therapy is sufficient for untreated CNS metastases, and early RT may need to be integrated into the treatment planning. An increasing number of studies investigate the role that emerging techniques, such as the sequencing of tumor DNA from resected brain metastases tissue or cerebrospinal fluid or radiomics-based analysis of CNS imaging, can play in guiding treatment approaches.
    Conclusions and Relevance: With multiple generations of targeted therapies now available, the treatment for CNS metastases should be tailored to the patients with consideration given to molecular testing results, CNS penetrance of systemic therapy, patient characteristics, and multidisciplinary review. More research is needed in understanding the clonal evolution of CNS metastases, and the development of novel therapeutics with CNS efficacy.
    DOI:  https://doi.org/10.1001/jamaoncol.2024.5218
  2. Dermatology. 2024 Nov 27. 1-11
    Perineural invasion for risk stratification in cutaneous squamous cell carcinoma: a scoping review.
    Emmy C Crüts, Myrthe M G Moermans, Myrurgia Abdul Hamid, Patty J Nelemans, Klara Mosterd.
       INTRODUCTION: Microscopic perineural invasion (mPNI) is a histopathological characteristic that can be found in cutaneous squamous cell carcinoma (cSCC). In the eight edition of the American Joint Committee on Cancer (AJCC), mPNI defined as the involvement of nerves ≥0.1mm and nerves deeper than the dermis is included in risk stratification of cSCC. The question remains whether other mPNI features are important for optimal cSCC staging. We aim to summarize the evidence from published studies on the independent association between various mPNI features and the risk of recurrence, metastasis and disease-specific death in patients with cSCC.
    METHODS: Embase, PubMed, and Web of Science were searched from January 2023 to February 2024 to identify studies that reported the prognostic impact of mPNI features in patients ≥18 years with histopathologically verified cSCC. Data on study and tumour characteristics were extracted.
    RESULTS: Nineteen studies met the inclusion criteria and evaluated one or more mPNI features in cSCC including nerve diameter, the extent of mPNI, the number of affected nerves, and depth of mPNI. Two studies provided evidence that 'mPNI ≥0.1mm' and 'mPNI deeper than the dermis' are significantly and independently associated with poor prognosis after correction for other mPNI features and high-risk factors. One of these studies additionally identified 'involvement of ≥3 nerves' as an independent and significant predictor of higher risk of local recurrence (HR, 2.17; 95% CI, 1.03-4.56; p=0.04).
    CONCLUSION: Besides 'nerve diameter of ≥0.1mm' and 'depth of mPNI involvement', 'involvement of multiple nerves' was found to be an independent risk factor for poor prognosis and should also be considered for appropriate risk stratification.
    DOI:  https://doi.org/10.1159/000542772
  3. Cancers (Basel). 2024 Nov 12. pii: 3796. [Epub ahead of print]16(22):
    Survival and Treatment Outcomes in Gastric Cancer Patients with Brain Metastases: A Systematic Review and Meta-Analysis.
    Daniel Sur, Adina Turcu-Stiolică, Emil Moraru, Cristian Virgil Lungulescu, Cristina Lungulescu, Vlad Iovanescu, Petrica Popa.
       BACKGROUND: Brain metastases (BM) from gastric cancer (GC) are rare but associated with poor prognosis, significantly impacting patient survival and quality of life. The objective of this systematic review and meta-analysis is to consolidate existing research on BM from GC, evaluate the incidence and clinical outcomes, and explore the effectiveness of treatment options.
    METHODS: A systematic search was conducted across the Medline, Web of Science, and Scopus databases, following PRISMA guidelines. Eighteen high-quality studies, as per the Newcastle-Ottawa Quality Assessment Scale, were included, encompassing 70,237 GC patients, of whom 621 developed BM. Data on progression-free survival (PFS), overall survival (OS), neurological symptoms, and HER2 status were analyzed using a random-effects model.
    RESULTS: The incidence of BM in GC patients was found to be 2.29% (95% CI: 1.06-3.53%), with the range extending from 0.47% to 7.79% across studies. HER2-positive status was significantly associated with a higher likelihood of developing BM, with an odds ratio of 43.24 (95% CI: 2.05-913.39; p = 0.02), although this finding was based on limited data. The surgical resection of BM was linked to significantly improved survival outcomes, with a mean difference in OS of 12.39 months (95% CI: 2.03-22.75; p = 0.02) compared to non-surgical approaches.
    CONCLUSIONS: The surgical resection of brain metastases in GC patients significantly enhances overall survival, while HER2-positive patients may show a higher risk for developing BM. These findings underscore the importance of tailored therapeutic approaches for GC patients with BM.
    Keywords:  HER2; brain metastases; gastric cancer; incidence; overall survival; radiotherapy; surgery
    DOI:  https://doi.org/10.3390/cancers16223796
  4. Neuropeptides. 2024 Oct 16. pii: S0143-4179(24)00078-7. [Epub ahead of print]109 102479
    NK1 receptor blockade disrupts microtumor growth and aggregation in a three-dimensional murine breast cancer model.
    Silvia Gutierrez, M Danilo Boada.
      Several data indicate that Substance P (SP) neurokinin type 1 receptor (NK1R) is at the center of the interaction between cancer cells and peripheral sensory neurons. Selecting the appropriate cancer cell line and its susceptibility to being modulated by NK1 antagonists are critical to studying this complex interaction. In the current study, we have focused on this selection by comparing several aspects of the triple-negative breast cancer (TNBC) cell line (MDA-MB-231LUC+) with a modified murine cell line (E0771LUC+), both expressing luciferase. This comparison was made using several methods, SP stimulation and 3D cell culture models, to better reproduce the heterogenous microenvironment of solid tumors observed in vivo. Furthermore, the susceptibility of the murine cell line (E0771LUC+) to NK1R antagonist (Aprepitant) was tested. Our results indicate that E0771LUC+ recapitulates several essential aspects of the human cell line, rendering this murine line ideal to be used on immune-competent animals during in vivo studies. We have also found that both cell lines are susceptible to SP stimulation, and their proliferation is disrupted by NK1R antagonists (Aprepitant). In vivo studies are required to verify and refine these findings.
    Keywords:  Aprepitant; Breast cancer; Microtumors; NK1R; Neuropeptides; Substance P
    DOI:  https://doi.org/10.1016/j.npep.2024.102479
  5. Medicine (Baltimore). 2024 Nov 29. 103(48): e40673
    Development of a nomogram for predicting cancer pain in lung cancer patients: An observational study.
    Yuewen Li, Zhiyong Wang, Chuxiong Gong, Yingsong Zhang, Ling Fu, Bencheng Wu, Weifang Wang, Yilin Chen, Kunzhong Zhou, Li Zhuang.
      During the progression of lung cancer, cancer pain is a common complication. Currently, there are no accurate tools or methods to predict the occurrence of cancer pain in lung cancer. Our study aims to construct a predictive model for lung cancer pain to assist in the early diagnosis of cancer pain and improve prognosis. We retrospectively collected clinical data from 300 lung cancer patients between March 2013 and March 2023. First, we compared the clinical data of the groups with and without cancer pain. Significant factors were further screened using random forest analysis (IncMSE% > 2) to identify those with significant differences. Finally, these factors were incorporated into a multifactorial logistic regression model to develop a predictive model for lung cancer pain. The predictive accuracy and performance of the model were assessed using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) analysis. Our study collected data from 300 lung cancer patients, including 100 in the pain-free group and 200 in the pain group. Subsequently, we conducted univariate analysis on 22 factors and selected statistically significant factors using random forest methods. Ultimately, lymphocytes(LYM) percentage, bone metastasis, tumor necrosis factor alpha (TNFα), and interleukin-6 (IL6) were identified as key factors. These 4 factors were included in a multivariate logistic regression analysis to construct a predictive model for lung cancer pain. The model demonstrated good predictive ability, with an area under the curve (AUC) of 0.852 (95% CI: 0.806-0.899). The calibration curve indicated that the model has good accuracy in predicting the risk of lung cancer pain. DCA further emphasized the model's high accuracy. The model was finally validated using 5-fold cross-validation. We developed a reliable predictive model for cancer pain in lung cancer. This can provide a theoretical basis for future large-sample, multi-center studies and may also assist in the early prevention and intervention of cancer pain in lung cancer.
    DOI:  https://doi.org/10.1097/MD.0000000000040673
  6. Neuromodulation. 2024 Nov 25. pii: S1094-7159(24)01196-6. [Epub ahead of print]
    Neurostimulation for the Treatment of Cancer-Induced Pain: A Scoping Review.
    Peter D Vu, Steven Mach, Saba Javed.
       OBJECTIVES: Cancer pain is among the most prevalent and challenging symptoms in cancer care, with up to 95% of patients with late-stage cancer experiencing moderate-to-severe pain. Conventional pharmacologic treatments, including opioids, carry risks, and patients' conditions may be refractory to medical management or have contraindications. Neurostimulation techniques, such as spinal cord stimulation (SCS), dorsal root ganglion stimulation (DRGS), and peripheral nerve stimulation (PNS), have shown promise in treating treatment-induced cancer pain. However, a comprehensive review focusing on these techniques for cancer-induced pain alone is necessary.
    MATERIALS AND METHODS: A comprehensive literature review was conducted using Medline, Embase, and Cochrane Library data bases, focusing on studies from 2000 onward. Inclusion criteria included interventional and observational studies reporting on SCS, DRGS, and PNS in cancer-induced pain. Studies addressing treatment-induced pain, systematic reviews, meta-analyses, and non-English studies were excluded. Data were extracted and evaluated using the Grades of Recommendation, Assessment, Development, and Evaluation system.
    RESULTS: The search yielded 831 references, with 24 studies meeting the inclusion criteria. Sixteen studies focused on SCS, seven on PNS, and two cases on DRGS. SCS showed significant pain reduction, with an average decrease in numeric rating scale (NRS) scores from 8.0 to 2.2 over an average 8.4-month follow-up period. PNS also indicated substantial pain relief, with NRS scores decreasing from 8.29 to 3.04 over an average 5.2-month follow-up period. DRGS, although less studied, showed a reduction in NRS scores from 6.0 to 1.0 over an average 6.0-month follow-up period. SCS was associated with a significant reduction in opioid use, with average reported morphine equivalent daily dose (MEDD) change from 1152.2 mg to 739.7 mg over an average 5.0-month period, whereas PNS and DRGS had limited impact on opioid consumption, with no reported MEDD change.
    CONCLUSIONS: Our scoping review synthesizes evidence on neurostimulation interventions for treating cancer-induced pain. Current evidence suggests that interventions such as SCS, DRGS, and PNS may provide clinically meaningful pain relief in patients with cancer-induced pain. Several studies also reported improvements in functionality and quality of life. However, the level of evidence is limited owing to the lack of prospective comparative studies, clinical and methodologic heterogeneity, and small sample sizes.
    Keywords:  Cancer-induced pain; dorsal root ganglion stimulation; neuromodulation; peripheral nerve stimulation; spinal cord stimulation
    DOI:  https://doi.org/10.1016/j.neurom.2024.10.006
  7. Front Pharmacol. 2024 ;15 1423502
    β-blockers and statins: exploring the potential off-label applications in breast, colorectal, prostate, and lung cancers.
    Pedro Gabriel Senger Braga, Janaína da Silva Vieira, Aline Rachel Bezerra Gurgel, Patricia Chakur Brum.
      Despite advances in cancer treatment, current cancer incidence and prevalence still demand multimodal treatments to enhance survival and clinical outcomes. Drugs used in cardiology, such as β-blockers and statins have gained attention for their potential roles in oncology. This review focused on their possible complementary use in solid tumors, including breast, colorectal, lung, and prostate cancers. The involvement of the autonomic nervous system in promoting tumor growth can be disrupted by β-blockers, potentially hindering cancer progression. Statins, known for their pleiotropic effects, may also inhibit cancer growth by reducing cholesterol availability, a key factor in cell proliferation. We will provide an update on the impact of these therapies on cancer treatment and surveillance, discuss the underlying mechanisms, and explore their effects on the heart, contributing to the growing field of cardio-oncology.
    Keywords:  drug repositioning; solid cancer; statin; survival; β-blockers
    DOI:  https://doi.org/10.3389/fphar.2024.1423502
  8. Cancers (Basel). 2024 Nov 07. pii: 3757. [Epub ahead of print]16(22):
    Perioperative Observations and Outcome in Surgical Treatment of Malignant Peripheral Nerve Sheath Tumors.
    Julian Zipfel, Jonas Tellermann, Kevin Paul Ferraris, Florian Grimm, Antje Bornemann, Benjamin Bender, Helmut Dittmann, Jürgen Schäfer, Konstantin Nikolaou, Ruth Ladurner, Volker Steger, Marcos Tatagiba, Martin U Schuhmann, Isabel Gugel.
       BACKGROUND/OBJECTIVES: This retrospective observational study aimed to investigate the perioperative outcome in Malignant Peripheral Nerve Sheath Tumors (MPNSTs) with and without relation to Neurofibromatosis Type 1 (NF1) and to detect possible influencing factors.
    METHODS: Clinical reports, histopathological evaluations, imaging, and treatment characteristics were reviewed in 35 operated MPNSTs in 33 patients. Possible predictive valuables included disease type, preoperative tumor volume, SUV and MIB-1 proliferation index, resection margins, the presence of metastasis, and whether radio-/chemotherapy was received.
    RESULTS: Patients with NF1 were younger (mean age: 29 ± 13, 8-54 years) than sporadic cases (mean age: 45 ± 13, 24-67 years) and exhibited significantly larger preoperative tumor volumes (mean 299 vs. 18 cm3, p = 0.048). Most tumors were located in the facial/cervical/neck area (34%, n = 12), followed by the trunk (31%, n = 11), lower extremity (17%, n = 6), upper extremity (14%, n = 5), and intraspinal area (3%, n = 1). NF1-associated MPNSTs appeared predominantly on the trunk (39%) and sporadically in the facial/cervical/neck area (50%). Complete resection was possible in 66% and an improvement in or stability of function was achieved in most cases (motor 69%, sensory 74%), as well as a decrease in pain intensity (63%). NF1-associated MPNSTs exhibited more severe pain scores (median VRS scale 2, p = 0.002) compared to sporadic tumors (median VRS scale 0.5). Sporadic MPNSTs located at the head/facial/brachial plexus and upper extremities exhibited better preoperative functions compared to those on the lower extremities. In 12 cases with available [18F]FDG PET, the mean preoperative SUV (9.8 ± 7.2) positively correlated with the mean maximum MIB-1 index (34 ± 26%, p = 0.005) and the mean preoperative tumor volume (474.7 ± 68.6 cm3, p = 0.047). The overall survival (OS) was significantly longer in tumors with higher resection extents (R0, p = 0.01) and without accompanying metastasis (p = 0.046), and tended to be longer, but not significantly so, in sporadic MPNSTs. In six and seven tumors, with R1/R2 resection margins and present metastasis, respectively, solid or combined neo-/adjuvant radio-/chemotherapy led to a significantly shorter OS (p = 0.014).
    CONCLUSIONS: NF1-associated MPNSTs have larger tumor volumes, higher SUVs and MIB-1 proliferation indices, and a shorter overall survival period. Nevertheless, surgery can improve symptoms, particularly medication-resistant pain, and should also be considered in advanced disease for symptom control/improvement.
    Keywords:  FDG-PET; MIB-1; malignant peripheral nerve sheath tumor; neurofibroma; neurofibromatosis type 1; surgery
    DOI:  https://doi.org/10.3390/cancers16223757
  9. J Surg Case Rep. 2024 Nov;2024(11): rjae694
    Obturator nerve schwannoma: a case report and review of the robotic literature.
    Haley Bayne, Richard Q Vuong, Shubhneet Bal, Jeffrey West, Anya Laibangyang, David Doo.
      Obturator schwannomas are rare and often misdiagnosed as intraperitoneal pelvic masses. The optimal surgical approach for their resection is unclear. This study presents a case demonstrating the safe use of robotics for resecting a benign pelvic schwannoma and reviews the literature on robotic cases. Here, a 40-year-old woman with right lower quadrant pain underwent imaging, revealing a 4.6 × 3.3 × 3.6 cm pelvic mass. She had a robotic-assisted laparoscopic excision, with pathology confirming a benign schwannoma. Complete tumor resection is the gold standard. The use of minimally invasive robotic-assisted surgery is increasing due to improved visualization, efficient movement, and safety, making it a viable option for resecting obturator schwannomas.
    Keywords:  S100; obturator nerve; retroperitoneal schwannoma; robotic; schwannoma
    DOI:  https://doi.org/10.1093/jscr/rjae694
  10. Int J Surg Case Rep. 2024 Nov 16. pii: S2210-2612(24)01403-2. [Epub ahead of print]126 110622
    Six year natural progression of a clinically monitored retroperitoneal schwannoma: A case report.
    Elizabeth Kruse, Allye Gardner, Eduardo Vaca, Megan McNally.
       INTRODUCTION AND IMPORTANCE: Schwannomas arise from Schwann cells, which make up the neural sheath of peripheral nerves. These tumors are usually seen in the head, neck and flexor surfaces, but can arise in the retroperitoneal space on rare occasions. This case gives the unique opportunity to watch the long term progression and speed of growth of this rare tumor and the development of symptoms over time.
    CASE PRESENTATION: Here, we describe the interesting case of a retroperitoneal Schwannoma discovered incidentally that was then monitored over the course of six years. After the tumor grew from 2.4 × 2.2 cm to 5.4 × 5.2 cm over this time, symptoms such as abdominal pain, nausea, constipation, increased urinary frequency, and left leg paresthesia arose, prompting for removal of the tumor. On follow-up two weeks later, the patient reported resolution of symptoms.
    CLINICAL DISCUSSION: Treatment for this tumor is either immediate excision or the "watch and wait" method, as this tumor has a low rate of malignant transformation. The tumor discussed in this case had a higher rate of growth before removal when compared to other studies examining retroperitoneal Schwannoma development.
    CONCLUSION: The "watch and wait" method of treatment for this benign tumor is effective, but it is important to ensure the patient is aware that the tumor will likely continue to grow. Given this, the patient should be informed of possible mass effect symptoms to monitor for.
    Keywords:  Case report; Natural progression of disease; Open resection; Retroperitoneal schwannoma
    DOI:  https://doi.org/10.1016/j.ijscr.2024.110622
  11. Medicine (Baltimore). 2024 Nov 29. 103(48): e40745
    Fatal abdominal hemorrhage following surgery to remove a retroperitoneal MPNST associated with NF1: A case report.
    Yu-Yang Pei, Tian-Tong Yang, Hai-Dong Zhang, Tian-Shui Yu.
       RATIONALE: Individuals diagnosed with neurofibromatosis type I (NF1) commonly present with neurofibromas, and a subset may progress to develop malignant peripheral nerve sheath tumors (MPNST) during their lifetime. Diagnosing and treating MPNST, typically linked to NF1, poses challenges for clinicians due to its histopathological complexity.
    PATIENT CONCERNS: A 25-year-old male presented with postprandial discomfort and vomiting, subsequently developing left mid-abdominal pain.
    DIAGNOSES: The patient was admitted to the hospital, where a low-density retroperitoneal mass was detected via computed tomography (CT). Histopathological examination revealed spindle-shaped tumor cells characterized by abundant cytoplasm and highly pigmented nuclei, demonstrating pathological nuclear division. The tumor cells exhibited partial cytoplasmic positive for S-100 and focal cytoplasmic positive for cytokeratin (CK) and desmin, as determined by immunohistochemical staining. Genetic analysis of blood and extracted tissues identified an NF1 missense mutation. Prior research corroborated the pathological diagnosis of MPNST exhibiting both epithelial and myogenic differentiation.
    INTERVENTIONS: A retroperitoneal mass excision was conducted, revealing a mass located in the retroperitoneal omental sac.
    OUTCOMES: Approximately 5 hours after surgery, the patient's blood pressure exhibited a gradual decline. An emergency laparotomy was conducted. Approximately 3000 mL of blood was identified in the upper abdominal cavity. The patient's blood pressure consistently declined and ultimately resulted in death after 2 days.
    LESSONS: It is crucial to assess the potential for heterogeneous differentiation in MPNST during pathological diagnosis. In the treatment of MPNST with heterogeneous differentiation, particularly in cases with significant tumor bulk, surgeons must anticipate potential hemorrhagic complications and adopt a cautious approach to surgical intervention.
    DOI:  https://doi.org/10.1097/MD.0000000000040745
This page is being maintained by Thomas Krichel. It was last updated on 2024‒12‒10 at 1:07.