Clinical Programs Update

The Neuroimmune Axis Disorders Program is a national destination precision diagnostics and personalized medicine program led by Laura A. Pace MD, PhD that focuses on complex chronic illnesses that impact the nervous, immune, endocrine, and gastrointestinal systems. Neuroimmune axis disorders disproportionately and more severely impact females and often have an onset after an immune activating event such as an infection, major hormone change, surgery, concussion, or physical trauma.

Neuroimmune axis disorders share many common overlapping core phenotypes, which make it difficult to obtain accurate diagnoses. These conditions often involve:

• Immune dysregulation
• Neurogastrointestinal dysregulation
  
• Autonomic nervous system dysregulation
• Extracellular matrix | connective tissue dysregulation
• Endocrine dysregulation
• Chronic pain
• Cognitive impairment
• Fatigue
  
  

The Neuroimmune Axis Disorders Program focuses on understanding the underlying biology of disease, allowing for targeted personalized treatments. The complex, multisystem nature of these conditions requires the integration of information across multiple domains to properly diagnose and identify personalized disease modifying therapeutic interventions.

The Precision Diagnostics Program offers state of the art testing to provide accurate diagnosis of neuroimmune axis disorders.

• Current tools
  • Genetics/Genomics: Whole genome sequencing is used to identify potential genetic causes and risk factors of various neuroimmune axis disorders. 
  • Immune System Profiling:  We combine deep immune profiling of innate and adaptive cells and immune system mediators to understand to role of immune system dysregulation in disease.
  • Autoantibody detection:  New therapies allow for effective treatment ofautoantibody associated diseases.
    
    
• Future tools
• • Spatial Multiomics: Identification of neuroimmune axis biomarkers using spatial multiomics (transcriptomics, proteomics, and metabolomics) to provide insight into disease mechanism.

The Personalized Medicine Program provides access to individualized treatment and therapies based on the results from the Precision Diagnostics Program

• Current therapies
  

Drug Repurposing: There has been a recent renaissance in medications that modulate the immune and nervous systems that can be repurposed to treat neuroimmune axis disorders.

• Future therapies
  • Bioelectronic Medicine: There have been recent breakthroughs in using electromagnetic stimulation in treating various diseases. The Personalized Medicine Program will offer transcranial magnetic stimulation (TMS), vagal nerve stimulation (VNS), and translumbosacral neuromodulation therapy (TNT) as treatment options.
  • Clinical Trials: In many cases results from the Precision Diagnostics Program provide insights into potential treatment pathways for neuroimmune axis disorders. We are working with various biopharma and biotech companies to provide patients access to medications and treatments through clinical trials.

1. Initial Visit
   • The initial patient visit should be virtual. The team can then formulate a comprehensive testing strategy in advance of an in person visit to Stanford University.
   • Virtual visits can occur for patients located in the following states: AZ, CA, CO, FL, GA, ID, IN, MD, MN, MO, MT, NJ, NV, TN, TX, UT, WA, WY, with others in process.
      
2. Precision Diagnostics Program
   • Testing ordered through the Precision Diagnostics Program are coordinated and performed at Stanford University.
     
     
3. Personalized Medicine Program
   • After undergoing the precision diagnostics program the care team will work with patients to identify the best treatment plan for their case. This might require administration and observation at Stanford University. 
     
     
4. Patient Follow-up Care
   • Patients are usually able to schedule virtual follow-up visits with the care team.

The Neuroimmune Axis Disorders Program is always looking to partner with physicians and scientists from various disciplines to provide patients with worldclass care.

What is Transplant Oncology: Transplant oncology is a new and unique concept that combines multiple disciplines of liver transplant medicine, and oncology, essentially using liver transplantation as a curative option for treatment of liver cancers.

The primary objective of transplant oncology is to carefully select patients who are most likely to benefit from a liver transplant. The selection process aims to identify individuals with localized liver tumors who are less likely to experience cancer recurrence following transplantation. By doing this, transplant oncology seeks to enhance overall patient outcomes and survival rates, providing a potentially life-saving option for those facing the dual challenges of liver disease and cancer.

Multidisciplinary collaboration: This field requires close collaboration between hepatobiliary medical and surgical oncologists, transplant surgeons, transplant hepatologists, interventional radiologists and other specialists including radiation oncologists, pathologists, social workers, and nurse navigators to assess patient eligibility, manage treatment, and monitor for complications during pre- and post-transplant period. 

Main Applications: Historically, the most common application of transplant oncology has been liver transplantation for patients with early and intermediate-stage hepatocellular carcinoma (HCC). However, in the very recent years, the field has expanded the applications and following cancers could potentially be candidates for liver transplant:

• Advanced Hepatocellular carcinoma (HCC) under the All-Comers’ protocol (tumor burdens outside UNOS downstaging criteria)
• Unresectable perihilar cholangiocarcinoma
• Unresectable colorectal cancer liver metastasis
• Unresectable neuroendocrine tumor liver metastasis (NELM)
• Unresectable intrahepatic cholangiocarcinoma
• Unresectable Gastrointestinal Stromal tumor liver metastasis
• Unresectable hepatic adenomatosis
• Hepatic epithelioid hemangioendothelioma (HEHE)
  
  

Strict selection criteria: Patients must meet specific criteria regarding tumor size, stage, biology, lack of extrahepatic disease, and overall candidate’s health to be considered for a transplant via a close collaboration with GI and hepatobiliary oncologists and surgeons.

At Stanford, presence of two dedicated liver tumor boards plays a crucial role in the multidisciplinary approach to managing liver cancer patients. These boards focus of distinct stages of cancer:

1. Early/intermediate cases Tumor Board: Cases discussed here typically involve tumors that are smaller size HCC.
   
   
2.  Advanced HPB Tumor Board: Patients discussed may have either larger HCC tumors or non-HCC tumors such as cholangiocarcinoma, and all other indications listed above. These patients require neo-adjuvant liver-directed or systemic therapies prior to qualifying for LT. The team collaboratively consider a personalized treatment plan for individuals.  

Clinical Guidance: At Stanford liver transplant program, we have developed standardized protocols for patient evaluation, transplant selection criteria, conditioning regimens, and post-transplant management based on evidence-based practice. 

Initial Patient Referral Process

• Patients with liver masses or suspected liver cancer are initially referred to Stanford’s Liver Mass Clinic and Hepatobiliary Oncology Clinic. This can be initiated by primary care providers or specialists such as gastroenterologists, hepatologists, or oncologists.
• At these clinics, patients undergo a thorough assessment that may include diagnostic multiphasic CT or MRI, clinical evaluation, and lab work.
• Only a minority of patients would require a targeted liver biopsy for diagnosis confirmation.
• Depending on the tumor type, patients would require either cross-sectional imaging and/ or PET-CT for staging to exclude presence of extrahepatic disease.
• Cases are discussed at the tumor boards for treatment planning.
• Patients who meet the criteria for lT will go through Pre-LT work up and be approved for listing. There are different UNOS policies for granting MELD exception points depend on the tumor type.
•  

Monitoring of waitlisted patients: To prevent waitlist dropout due to cancer progression, waitlisted patients require ongoing treatment with either systemic therapies (i.e. chemotherapy for colorectal cancer patients or immunotherapy/chemo for patients with HCC or Cholangiocarcinoma) or liver-directed therapies (via interventional radiology or radiation oncology modalities). Patients receive surveillance imaging every 2-3 months and are reviewed at the tumor boards.

Research and clinical trials: The transplant oncology team actively engage in research aimed at exploring new treatment strategies, identifying biomarkers to predict transplant outcomes, and improving patient outcome.

We have ongoing multicenter collaboration with major transplant centers to study patient’s outcome while pushing the boundaries of transplant indications.

We have close collaboration within our Stanford cancer research labs in exploring new biomarkers and molecular targets in diagnosing and treatment of liver cancers.

Active participation with our Stanford hepatobiliary oncology team allows integration of clinical research into patient care. By enrolling patients in multiple active clinical trials, the team can enhance access to innovative treatments.