Precision Neuroendocrine Cancer
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Early, Late-Stage, and Metastatic Neuroendocrine Cancer Treatment Options

A neuroendocrine cancer diagnosis does not mean your options are limited because you have a rare disease. At Envita Medical Centers, a world-class integrative center for Precision Oncology, we overcome the standard treatment challenges of this uncommon type of cancer, which is in the United States.

In our clinical practice of over 20 years, we have been able to help complicated, late-stage, and refractory to care cancer patients with our proprietary precision-targeted treatment options, aimed at tackling the core of their unique neuroendocrine cancer. Envita’s suite of innovative new treatments, including CIPI™ (Chemo Immuno Precision Injections) and GTFC™ (Genetically Targeted Fractionated Chemotherapy), go beyond standard treatments like chemotherapy, radiation, embolization, and Peptide Receptor Radionuclide Therapy (PRRT), to help even those with unresectable and advanced neuroendocrine tumors.

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Susan Booth came in a wheelchair to Envita, but walked out of our doors, cancer-free!

Susan’s cancer started in the pelvic region, but Neuroendocrine neoplasms (NENs)- including Neuroendocrine Tumors (NETs) and Neuroendocrine Carcinomas (NECs), may manifest in any part of the body. Depending on the cancerous cells’ degree of differentiation from the healthy cells, they are either known as NETs, which are well-differentiated, or NECs, which are poorly differentiated. NENs’ incidence is common in the lungs, gastrointestinal tract, or the pancreas, and the symptoms of cancer vary depending on the site, size, stage, type, and grade of tumor.

This article deals with all aspects of Neuroendocrine Cancer, including:

How Envita Overcomes Challenges of Standard Treatment Options

Diagnosis and treatment of patients with this relatively rare form of cancer can be challenging due to its wide variety of symptoms, and in several cases, this lack of timely intervention causes disease progression. Medical studies on the prognosis of neuroendocrine carcinomas of the colon, rectum, and anal canal show poor results [2] when following conventional care, but with our personalized precision oncology treatment options, patients may have a better chance of progression-free survival and a holistic recovery.

Envita’s precision oncology program not only takes into account extensive genomics, but it also includes an advanced immune system evaluation to custom-build protocols for each patient, which is especially crucial in treating rare cancers, like neuroendocrine carcinomas.

Our powerful combinations of leading-edge conventional treatments along with research-based natural therapies may be beneficial, even when resection is not an option for patients.

Envita’s expert team has been able to help improve outcomes, by precision-targeting each patient’s specific cancer expressions, instead of using the one-size-fits-all standard NCCN (National Comprehensive Cancer Network) guidelines, followed in major hospitals and cancer centers across the country.

The NCCN guidelines dictate care regimens based on certain criteria, such as, primary site, tumor functionality, somatostatin receptor status, and mitotic count for grade and degree of differentiation, which determines whether the tumors are poorly differentiated neuroendocrine carcinomas or well-differentiated neuroendocrine tumors. However, in our clinical opinion, these criteria may not be enough to strike out the disease and the unique set of causes responsible for its growth and spread in each individual patient. To overcome this challenge, Envita, being a truly integrative clinic, breaks away from the one-size-fits-all NCCN guidelines and offers personalized precision oncology treatments to all its patients.

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Standard NCCN guidelines allow precision oncology treatments only as a follow-up to failed first-line treatments, but this delay may lead to devastating consequences in a life-threatening disease like cancer. However, Envita’s team is not limited by these restrictions which is why we utilize personalized precision oncology treatments to target cancerous cells from all possible angles.

At Envita, every patient gets access to Personalized Precision Oncology, right at the gate!

Even the handful of patients who receive standard precision oncology care do not get the benefits of Envita’s detailed and personalized precision oncology neuroendocrine cancer program. At Envita, we analyze many more parameters than those in standard precision oncology, to customize a treatment protocol aimed at each patient’s holistic recovery.

Envita Precision Algorithm vs.
Standard Oncology Precision Testing

Personalized Precision Oncology to Improve Overall Survival

Personalizing precision oncology treatments is crucial to improve overall survival, as cancer is a disease of genetic mutations and not of tissues or organs, and genetics vary from person to person. With varied genetics, cell mutations may lead to different cancer expressions, which explains why people with the same cancer type, stage, grade, and site may not respond similarly to the same treatment.

For instance, not everyone with the same site, stage, grade, and type of neuroendocrine cancer has the exact same cancer biomarkers, pointing to the need for personalizing precision oncology. Biomarkers refer to the proteins, genes, and other molecules which affect your unique endocrine cancer’s growth and spread to surrounding lymph nodes, liver, or other distant regions of the body. Patients with neuroendocrine carcinomas are prone to experiencing liver metastases or metastatic disease in other organs of the digestive system, as NETs commonly develop in and around the gastrointestinal tract.

A medical review on “Unmet Needs in High-Grade Gastroenteropancreatic Neuroendocrine Neoplasms (WHO G3) highlights how biomarkers for prognosis and treatment have to be developed and analyzing genetic molecular markers will be important [3]. However, at Envita, we have already developed proprietary tests for identifying many more biomarkers than standard tests, and we also utilize innovative technology for advanced analysis of genetic molecular markers. Incorporating such novel aspects into our program has led to the development of a suite of unique new treatments for all stages and types of neuroendocrine cancer patients.

Envita’s New Treatments for all Stages and Types of Neuroendocrine Cancers

Envita’s new treatments are designed on the N of 1 model, which enables our team of integrative physicians to customize treatment based on patient-specific biomarkers, with the goal of aggressively attacking their cancer, while reducing chances of side effects.

We personalize care at every level of our four-step precision oncology treatment approach to customize a unique medical blueprint for every patient. Building a patient-specific treatment plan enables us to target all the unique cancer expressions of each patient’s specific neuroendocrine cancer, which aims to improve quality of life, increase longevity, and reduce toxicity.

Knowing the origin of your cancer is essential to treat it at its core, and a detailed genomic identification helps to probe each patient’s specific mutations causing their cancer. NETs represent a spectrum of tumors with a diverse range of molecular abnormalities that share a common origin, which are neuroendocrine cells.

In certain patients, the disease could be the result of inherited genetic mutations, as a family history of cancer is considered a significant risk factor for all NETs [5]. In other instances, a long-term history of diabetes could be triggering mutations causing certain cases of GI NET as well as prolonged exposure to sunlight may initiate mutations leading to Merkel Cell Carcinoma.

At Envita, irrespective of your stage, type, or site of neuroendocrine cancer, we trace patient-specific irregularities down to the cellular and molecular level for establishing better treatment mechanisms. Medical studies show how genome-wide screening of different types of NETs is likely to generate new insights into the tumor biology [6], which is what we are doing here at Envita to precision-target the core of every patient’s specific cancer.

While attacking each patient’s specific neuroendocrine cancer biomarkers, it is critical to strengthen their immune system because it plays a crucial role in limiting cancer progression. A robust immune system can kill thousands of cancerous and precancerous cells in a day, but this ability gets impacted when you have a weak immune system. At Envita, we understand that cancer compromises the immune system of patients, which is why we identify immuno targets and include personalized immunotherapy for treating all stages, types, and grades of neuroendocrine cancers. Scientific studies prove how combining immunotherapy with chemotherapy can be beneficial for treating certain types of neuroendocrine cancers [7].

Ultra Analytes Liquid Biopsy

Ultra Analytes Liquid Biopsy is deployed to identify targeted immunotherapy options to help get your immune system working properly again. Learn more about Immunotherapy

Our Ultra Analytes Liquid Biopsy analyses the Circulating Tumor Cells (CTCs) in a patient’s blood sample to establish immuno and chemo targets, allowing us to proactively treat early signs of metastasis. CTCs break away from a growing tumor and enter the patient’s blood stream, spreading the cancer to different parts of the body.

A detailed examination of these CTCs enables us to track and treat the cancer in its micro-metastatic form, even before they manifest symptoms of spread. A liquid biopsy fulfills the criteria for real-time disease management and avoids the negative invasive implications and single time-point limitations of tissue biopsy [8].

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We not only manage your disease in real time, but we also harness your immune system’s innate ability to find and kill the cancer, via immunotherapy. According to a 2020 study on "Novel immunotherapy strategies for treatment of neuroendocrine neoplasms," immunotherapy has been unexplored in NENs until recently [9].

However, Envita’s expert team of researchers have been pushing the boundaries of science to innovate and discover advanced immunotherapies which are allowing patients to respond to care where they had not before. We go beyond the typical immunotherapy drugs, such as, PD-1 inhibitors, mTOR inhibitors, and interferons, to build next level immuno reactivation treatment plans, customized for each of our neuroendocrine cancer patients.

Step 3

Personalized Drug Design to Potentiate Treatment Regimens

At Envita, we use a powerful combination of FDA (Food and Drug Administration) approved drugs, repurposed drugs, and custom-compounded adjuvants to not only kill the cancerous cells, but also boost the immune system. Several studies, like the NETTER 1 trial show how combination of two types of drugs can be more effective than high doses of a single anti-cancer agent [10], which is why we have been utilizing our advanced technology to design various combination therapies suitable for each individual neuroendocrine cancer patient.

Learn more about Personalized Drug Design

FDA Approved Drugs

Optimized for your cancer mutations.

Repurposed Drugs

Off-label use of approved medications

Custom Compounded Adjuvants

Genetically typed for each patient.

Our personalized drug design helps to potentiate treatment regimens as the anti-cancer drugs available on the market may not always be effective against all the treatment targets identified through our extensive tests. To overcome this limitation, we custom-compound adjuvants at our in-house pharmacy. These custom-compounded adjuvants fill up the gap in treatment by impacting the biomarkers, for which there are no compatible medicines on the market.

We use advanced phytotherapeutics, comprising plant extracts and herbs to custom-design adjuvants with enhanced cytotoxicity for killing cancerous cells and debulking tumors, while helping to accelerate the healing process, for each individual patient. To potentially improve outcomes, we also adjust dosage of FDA approved and repurposed drugs, which helps in enhancing benefits of the anti-cancer medications and reducing their side effects.

Medical reviews indicate how managing certain types of neuroendocrine tumors is often complex and may include a combination of surgery, systemic treatments, and locoregional approaches [11]. To counter these treatment complexities, we have developed several new minimally invasive treatments to not only avoid highly invasive surgeries but to also widen options for patients with advanced and unresectable neuroendocrine cancers.

Depending on the site, size, grade, and type of tumor, our expert medical team determines a suitable precision deployment mode to administer anticancer medications with the intent of targeting only the cancerous cells and reducing impact to the surrounding healthy cells. At Envita, targeted therapies are not just one of the many treatment options, as all our patient-specific treatments are targeted to affect their unique neuroendocrine cancer.

Here are some of the innovative new treatments, which may be utilized by itself or in combination with other therapies to effectively treat each neuroendocrine cancer patient:

CIPI™ (Chemo Immuno Precision Injection)

CIPI™ (Chemo Immuno Precision Injections) is a revolutionary interventional radiology procedure for precision tumor chemoembolization. It is designed for deploying anti-cancer medications directly to difficult to reach tumors, such as hepatic, pulmonary, appendiceal, gastrointestinal, or pancreatic neuroendocrine tumors, which are common in neuroendocrine carcinoma patients.

Through this proprietary technology we deliver personalized chemotherapy and immunotherapy adjunctive agents to kill the cancerous cells, seal the tumor’s blood supply, and deactivate it. The neo antigens released by the deactivated tumor, triggers an immune system response to find and kill cancerous cells elsewhere in the body, reducing chances of a potential metastases. CIPI™ has proved exceptionally beneficial for many of our neuroendocrine carcinoma patients and helped them to progress in their journey towards a long-term remission.

Envita's CIPI™ vs.
Standard Surgery

GTFC™ (Genetically Targeted Fractionated Chemotherapy)

GTFC™ (Genetically Targeted Fractionated Chemotherapy) is our proprietary systemic therapy to deliver precision-targeted chemo medicines with the highest cytotoxicity for impacting each patient’s unique neuroendocrine carcinoma biomarkers. This intravenous procedure increases the mechanism of action against each patient’s unique cancer expressions by using a greater number of targeted chemotherapy agents than standard untargeted chemotherapy. Though GTFC™ uses more chemo agents, their dosage is lower than standard maximum therapeutic dosage chemotherapy, which is why many of our patients do not experience common side effects, such as weakness and nausea.

This intravenous precision deployment mechanism of genetically typed chemo and immuno agents increases its bioavailability, reducing the chances of impact on the healthy cells surrounding the cancerous cells. With the healthy cells remaining intact, there are fewer chances of depressed immunity and resultant side effects. A healthy and reactivated immune system is crucial to your holistic recovery because it is your first and last line of defense against neuroendocrine cancer relapse and metastasis.

Envita's GTFC™ vs.
Standard Chemotherapy

Hormone Therapy

Hormone therapy is used to check the release of excess hormones from neuroendocrine tumors often causing carcinoid syndromes, like diarrhea and flushed skin, but at Envita we go beyond standard somatostatin analogs and other medications to holistically treat our patients. Medical studies indicate how the use of certain agents may improve symptoms of carcinoid syndrome[12], but we focus on slowing down tumor growth and deactivating them as well, while checking excess secretions from tumors. We enhance the efficacy of these medicines by combining them with genetically typed immunotherapy agents and research-based phytotherapeutic medications.

Tumor Ablation

Ablation is another way of destroying tumors by utilizing either excess heat or cold. We use different types of tumor ablation techniques such as cryoablation, radiofrequency ablation, and microwave ablation to target each patient’s unique NET depending on its size, site, type, and grade.

A customized image-guided metal probe is injected into the tumor to freeze or heat and destroy the cancerous cells with either cooling agents, or microwaves or high-energy radio waves. At Envita, we optimize the benefits of these procedures by utilizing the antigens from the deactivated tumors to train your immune system in identifying and killing cancer cells elsewhere in the body, reducing chances of a potential metastasis.

Different Types of Neuroendocrine Cancers

Neuroendocrine cancers are divided into various types and sub-types based on their functionality and site of origin. They are as follows:

Functionality

• NENs begin in specialized neuroendocrine cells, with features of both hormone-producing endocrine cells and nerve cells
• Due to their origin in neuroendocrine cells, some neoplasms may be functional as the tumors produce excess hormones, while others are nonfunctional with no specific clinical symptoms in the early stages
• NENs can be functional or non-functional, irrespective of their site of origin

Sites of Origin

The following NETs are called Neuroendocrine Carcinomas (NECs), if the tumors comprise poorly differentiated cells:

• GI Tract NET used to be called carcinoid tumors: starts in the neuroendocrine cells of the GI tract
• Lung NET also used to be called carcinoid tumors: starts in the neuroendocrine cells of the lungs
• Gastroenteropancreatic Neuroendocrine Tumors (GEP NET) also known as carcinoid or islet cell tumors are further subdivided into:
  1. Foregut Tumors: starts in the neuroendocrine cells of esophagus, stomach, proximal duodenum, liver, and pancreas
  2. Midgut Tumors: distal duodenum ileum, jejunum, ascending colon, and proximal two thirds of transverse colon
  3. Hindgut Tumors: distal third of transverse colon, descending colon, sigmoid colon, and rectum
• Pancreatic NET (PNET), also known as islet cell tumors: starts in the neuroendocrine cells of the pancreas
• Markel Cell Carcinoma: starts in the Markel cells (type of skin neuroendocrine cells) of the top layer of skin
• Medullary Thyroid Cancer (MTC): starts in the thyroid gland
• Pheochromocytoma: starts in the adrenal gland
• Paraganglioma: starts outside of the adrenal glands

Symptoms of Neuroendocrine Cancer

Watch out for the following symptoms as any one or a combination of these symptoms could be manifestations of neuroendocrine cancers:

• Weight loss without trying
• Exhaustion
• Loss of appetite
• Nausea
• Lump or persistent pain in a specific part of the body
• Diarrhea
• Flushing
• Rashes
• Jaundice
• Excess or very low blood glucose levels
• Certain nutritional deficiencies
• Unusual bleeding

Our expert team comprising oncologists, interventional radiologists, researchers, and pharmacists, strives relentlessly to attack your unique neuroendocrine cancer from all possible angles. They undergo extensive training of over 1,500 hours in our personalized precision oncology approach to help you find the best possible treatment options for a holistic recovery. If you or your loved ones have any questions regarding neuroendocrine cancer, please contact us at: 866-830-4576. May God bless you on your journey to healing.

References

[1] Yao JC, Hassan M, Phan A, et al. One hundred years after "carcinoid": epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol. 2008;26(18):3063-3072. doi:10.1200/JCO.2007.15.4377

[2] Aytac E, Ozdemir Y, Ozuner G. Long term outcomes of neuroendocrine carcinomas (high-grade neuroendocrine tumors) of the colon, rectum, and anal canal. J Visc Surg. 2014;151(1):3-7. doi:10.1016/j.jviscsurg.2013.12.007

[3] Sorbye H, Baudin E, Borbath I, et al. Unmet Needs in High-Grade Gastroenteropancreatic Neuroendocrine Neoplasms (WHO G3). Neuroendocrinology. 2019;108(1):54-62. doi:10.1159/000493318

[4] Lillie EO, Patay B, Diamant J, Issell B, Topol EJ, Schork NJ. The n-of-1 clinical trial: the ultimate strategy for individualizing medicine?. Per Med. 2011;8(2):161-173. doi:10.2217/pme.11.7

[5] Hassan MM, Phan A, Li D, Dagohoy CG, Leary C, Yao JC. Risk factors associated with neuroendocrine tumors: A U.S.-based case-control study. Int J Cancer. 2008;123(4):867-873. doi:10.1002/ijc.23529

[6] Öberg K. The genetics of neuroendocrine tumors. Semin Oncol. 2013;40(1):37-44. doi:10.1053/j.seminoncol.2012.11.005

[7] Horn L, Mansfield AS, Szczęsna A, et al. First-Line [removed due to editorial restrictions] plus Chemotherapy in Extensive-Stage Small-Cell Lung Cancer. N Engl J Med. 2018;379(23):2220-2229. doi:10.1056/NEJMoa1809064

[8] Modlin IM, Kidd M, Malczewska A, et al. The NETest: The Clinical Utility of Multigene Blood Analysis in the Diagnosis and Management of Neuroendocrine Tumors. Endocrinol Metab Clin North Am. 2018;47(3):485-504. doi:10.1016/j.ecl.2018.05.002

[9] Al-Toubah T, Cives M, Strosberg J. Novel immunotherapy strategies for treatment of neuroendocrine neoplasms. Transl Gastroenterol Hepatol. 2020;5:54. Published 2020 Oct 5. doi:10.21037/tgh.2019.12.18

[10] Strosberg JR, Caplin ME, Kunz PL, et al. [removed due to editorial restrictions] plus long-acting [removed due to editorial restrictions] versus highdose long-acting [removed due to editorial restrictions] in patients with midgut neuroendocrine tumours (NETTER-1): final overall survival and long-term safety results from an open-label, randomised, controlled, phase 3 trial [published correction appears in Lancet Oncol. 2022 Feb;23(2):e59]. Lancet Oncol. 2021;22(12):1752-1763. doi:10.1016/S1470-2045(21)00572-6

[11] Laskaratos FM, Caplin M. Treatment challenges in and outside a network setting: Gastrointestinal neuroendocrine tumours. Eur J Surg Oncol. 2019;45(1):52-59. doi:10.1016/j.ejso.2018.03.012

[12] Pavel M, Hörsch D, Caplin M, et al. [removed due to editorial restrictions] for carcinoid syndrome: a single-arm, multicenter trial. J Clin Endocrinol Metab. 2015;100(4):1511-1519. doi:10.1210/jc.2014-2247

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