Blood Test and Cancer Spread in Children

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Abstract

Child cancer has become a very common disease, its death toll becoming increasingly high despite the treatment options that have been designed so far. Even though some of the current treatment options are rather efficient, the fast and uncontrollable process of cancer spreading prevents from carrying out the required procedures efficiently. Therefore, tests that allow determining the speed and aggressiveness of CC are required.

The use of a blood test as the most successful tool for defining the speed and severity of cancer metastasis should be viewed as the most promising option seeing that it isolates the biomarkers that create prerequisites for determining the severity and degree of the cancer spreading. The test in question, designed by the researchers at the Weill Cornell Medicine and Memorial Sloan Kettering Cancer Center (MSK), will ostensibly help isolate the proteins in the exosomes of the patient, therefore, leading to a more accurate prognosis and the identification of appropriate treatment response.

Introduction

Determining the stage at which the development of cancer in a child patient currently is can be deemed as crucial for the success of the further treatment (Brasme, Chalumeau, Oberlin, Valteau-Couanet, & Gaspar, 2014). The identified process is especially important in treating children since their immune system may fail to resist the detrimental effects of the cancer metastasis (Brasmeet al., 2014). Therefore, a test that will allow for more accurate identification of the current metastasis stage and, thus, defining the appropriate ways of managing the problem is crucial to the improvement of patient outcomes.

As a rule, biopsy has been used as the most common type of determining the stage at which a certain cancerous disease currently exists in a child patient, as well as defining the possible tools for addressing cancer appropriately (e.g., surgery, chemotherapy, etc.). However, a biopsy has proven to have a range of limitations that often affect the success of the chosen intervention and may even jeopardize the patient’s life. For instance, the accessibility of the tumor often defines the accuracy of the biopsy results and, thus, restricts the choice of appropriate therapy for the patient (Kowalik, Kowalewska, & Gozdze, 2017).

Furthermore, as an interventional procedure, a biopsy is likely to be very uncomfortable for children. Finally, the fact that biopsy can only be carried out using a comparatively small amount of the patient’s tissue may trigger errors in the analysis and, therefore, lead to deplorable effects: “Even when tissue can be collected, preservation methods such as formalin fixation can display high levels of C > T/G > A transitions in the 1–25% allele frequency range, potentially leading to false-positive results for molecular assays” (Ilie & Hofman, 2016, p. 420).

Biopsy also provides a set of rather restricted options for the measurement of the biological marker (biomarker) of cancer in children. Typically defined as the indicator of the stage of cancer development in patients, a biomarker needs to be studied extensively, which means that a significant amount of tissue is required for the analysis (Kowalik et al., 2017).

Consequently, there has been a need to introduce a more efficient and painless tool for carrying out the analysis of the cancer metastasis development in child patients. The introduction of an innovative approach to managing the problem is required so that the quality of care could be improved. Particularly, accurate identification of the stage of metastasis in the child patient should be viewed as the primary goal of the current endeavors. Considering a blood test as the possible foundation for building a comprehensive and much more efficient approach can be viewed is a possibility due to the increased opportunities for retrieving a greater volume of the analysis material and the reduction in the chances of an error (Ilie & Hofman, 2016).

Pediatric Cancer: Statistics and Reasons for Concern

Even though the strategies for preventing and addressing cancer in children have been evolving and improving, CC remains a major issue in contemporary healthcare. In the United States, two types of CC have proven to be the most common; these are leukemia and Brain and central nervous system cancer (BaNSC) (Centers for Disease Control and Prevention, 2017). The highest incidence rate is currently 8.4 per 100,000 children, whereas the highest death toll is 0.8 (Centers for Disease Control and Prevention, 2017).

Types of Pediatric Cancer

Unfortunately, child cancers (CCs) are extremely numerous, and new types thereof appear on a regular basis (Centers for Disease Control and Prevention, 2017). However, the existing CCs can be categorized based on their location and properties. Thus, four essential types of CCs can be identified.

Neuroblastoma. Occurring in immature blood cells, neuroblastoma develops in adrenal glands, spine, abdomen, or chest. Neuroblastoma is typically found in children aged 5 or younger.
Osteosarcoma. Typically found in the child’s bones, osteosarcoma is typically a very aggressive form of CC.
Acute lymphocytic leukemia (ALL). ALL is a form of rapidly spreading blood cancer, i.e., cancerous cells develop in the bone marrow of the patient.
Brain and CNS cancers. BaCNS cancers occur in the brain tissue and may come in the form of either malignant (cancerous) or benign tumors (Imbach, ‎Kuhne, ‎& Arceci, 2014).

Treatment Options

At present, a range of approaches to cancer treatment exist. The choice of the intervention strategy largely depends on the severity of the problem, the type and location of cancer, and the unique characteristics of the patient. Among the approaches that have been developed so far, eight essential types can be isolated.

Surgery

Implying a basic process of removing the tumor from the patient’s body with the help of surgery, the identified framework demands that the patient should be provided with either local, regional, or general anesthesia. In the process, the tumor is removed along with the nearby tissue and, possibly, the lymph nodes that may have been affected by the disease. Minimally invasive surgery, in turn, implies that a series of small cuts should be made instead of a large one (Rosland & Engelsen, 2015).

Radiation therapy

The identified approach implies that radiation is used to kill cancerous cells.

Chemotherapy

In chemotherapy, drugs are used as the means of killing cancerous cells and stopping the metastasis.

Immunotherapy

Seeing that cancer affects the immune system of a patient extensively, the use of immunotherapy-based approaches to managing the problem can be viewed as reasonable. By focusing on the enhancement of the immune system functions, a healthcare practitioner is likely to increase the patient’s chances to fight cancer successfully (Rosland & Engelsen, 2015).

Targeted therapy

Focusing on the changes in the cancerous cells, the targeted therapy approach implies that the growth in these cells should be hampered (Rosland & Engelsen, 2015).

Hormone therapy

Hormones are used as a tool for slackening the process of cancer growth (Rosland & Engelsen, 2015).

Stem cell transplant

Blood-forming stem cells are restored during the stem cell transplantation. Whether being autologous (i.e., coming from the patient) or allogeneic (i.e., coming from a donor), stem cells substitute the ones that have been affected by cancer in the bone marrow (Rosland & Engelsen, 2015).

Precision medicine

Implying that an analysis of the patient’s genetic makeup should be carried out, the identified approach suggests that the treatment strategy should be selected based on the unique characteristics of the patient’s health (Rosland & Engelsen, 2015).

Possible Issues to Address

Avoiding overtreatment

It should be borne in mind that the process of cancer treatment is likely to trigger significant side effects in patients. Therefore, while preventing the instances of aggressive cancer development, the identified approaches also create prerequisites for overtreating the indolent cancers that do not require intense measures in the first place. Consequently, the basis for developing comorbid issues triggered by the overdose of medications or overly invasive surgeries is created.

Overtreatment can be avoided by raising awareness about the subject matter. Furthermore, the importance of accurate cancer metastasis measurement must be stressed to nurses and healthcare practitioners. Once the scale of the cancer-related problem is identified accurately, the threat of overtreatment will be reduced (Bhatt & Klotz, 2016).

Tools for Predicting the Spreading of Cancer

Biopsy

The concept of biopsy includes the removal of tissue for its further examination.

They are circulating DNA

In the Circulating DNA test, the chromosomal rearrangements that are characteristic of the early stages of cancer are viewed as the primary biomarkers. Therefore, the identified changes in the arrangement of the DNA circulation can be deemed as the key method of determining the presence and progress of cancer in child patients.

The fact that the elements of the DNA proved to be efficient in determining the presence of malignant cells in the patient’s blood is viewed as quite unexpected by researchers: “We thought that [circulating tumor] DNA should be a good biomarker for recurrence of breast cancer, but it had not really been shown before. When we saw that, it was very exciting” (The tumor trail left in blood, 2016, p. 271). Nevertheless, the biomarkers in question are likely to become the primary means of identifying cancer at the earliest stages of its development. As a result, a rather efficient treatment option can be designed successfully (Thakur et al., 2014).

That being said, the Circulating DNA test lacks precision. Particularly, study results show that it provides limited information about the disease progression (The tumor trail left in the blood, 2016). The lack of efficacy that the test demonstrates in the case of a low-burden metastatic disease indicates that the said approach should not be viewed as the foundation for carrying out a metastatic analysis in children (Paredes et al., 2014).

Tumor exosomes examination (TEE)

Also known as liquid biopsy, the TEE approach can be viewed as an innovative option that will reinvent the approach toward detecting and controlling the development of CCs. By definition, an exosome is a “conserved complex of protein” (Sesma & Haar, 2014, p. 169), which takes an active part in the synthesis of the DNA (Zavesky et al., 2015). To be more specific, the application of the TEE approach implies that blood tests should be taken.

When considering the benefits of the TEE approach, one must mention that it is comparatively quick and virtually painless, especially compared to the traditional biopsy procedures (Katsuda, Kosaka, & Ochiya, 2014). Therefore, the TEE framework should be viewed as the primary tool for analyzing the metastasis of tumors in children. Furthermore, the fact that the identified approach allows monitoring the response of tumors to the corresponding treatments should be deemed as a crucial argument in favor of using the said tool as the foundation for analyzing tumor metastasis in young patients (Brasme et al., 2014).

It should be noted, though, that, even with the advantages that the TEE framework has to offer, its effects on determining the metastasis in young patients, particularly, children will require further research. While the existing studies show so far that the TEE method is the superior one due to the high levels of accuracy and the additional opportunities that it provides, the benefits for the child patients have not been explored fully yet. Therefore, it is imperative to carry out extensive studies on the subject matter.

Difficulties Associated with Enhancing the Accuracy of the Tests

Unfortunately, the current tests that are used to determine the severity of the issue and the state of the disease development cannot be considered accurate. A closer look at the approach that is currently explored as the possible leeway for improving the process of managing the needs of child patients with cancer will show that there are several aspects that have to be explored in depth.

Problems with isolating tumor exosomes

It should be noted, though, that, even with the incredibly massive opportunities for improving the quality of care and detecting the stasis of tumors in child patients, the TEE approach could use certain adjustments. Being a comparatively new model, the TEE framework requires further improvements so that the results that it delivers could be more precise. Particularly, the difficulties associated with the isolation of the tumor isozymes and exosomes deserve to be mentioned as the primary area of concern:

However, the isolation of tumor-derived exosomes, which are variable in size, and their separation from normal exosomes, remains particularly challenging when compared with isolating free-floating DNA or tumor cells, so it will take some time before the technique is mature enough to detect other forms of cancer (The tumor trail left in blood, 2016, p. 271).

Therefore, the further enhancement of the framework’s efficacy is required. Thus, the current measurement techniques will have to be refined so that the outcomes of the measurement process could become more accurate. As a result, the foundation for an accurate identification of the patient’s metastasis will be built, which is especially important when managing the needs of child patients with tumors.

Use of biomarkers

There are significant issues with the choice of the elements that can be deemed as the markers of the disease development when it comes to cancer-related tests (Mincheva-Nilsson & Baranov, 2014).

Opportunities Offered by TEE

Unlike the rest of the tools for testing the patients for the presence of circulating tumor cells, TEE creates premises for a significant rise in the accuracy of the results. The release of tumor exosomes, which occurs once a tumor starts developing, can be spotted among regular exosomes with the help of the tests developed by the experts at Weill Cornell Medicine: “Exosomes can be harvested from a patient’s blood, and potentially from other bodily fluids such as urine, which are even more convenient and easy to access than blood” (The tumour trail left in blood, 2016, p. 271).

Therefore, the TEE framework allows distinguishing between the two types of vesicles, therefore, creating the foundation for a much more accurate analysis and, therefore, a faster identification of the stage at which the disease currently is. With the opportunities for analyzing the metastasis of cancer in a much more detailed and precise manner, the TEE approach provides the foundation for developing a more efficient response, i.e., the design of the treatment that will allow for an improved patient outcome.

A closer look at the way in which the TEE tool uses exosomes will show that the approach in question, while having an admittedly high potential, may require further improvements and tests to be used is the means of determining the metastasis in children. According to the recent studies, a significant number of children with cancer tend to develop bone metastasis, which makes the chances of the process of treatment, as well as the further recovery, extremely slim (The tumour trail left in blood, 2016).

Particularly, the areas of metastasis will have to be identified in a more precise manner. For instance, children with medulloblastoma tend to have metastasis in the spinal cord, whereas, for child patients with osteosarcoma, there is a significant threat of having lung metastasis (The tumour trail left in blood, 2016). Furthermore, some of the child patients may show no signs of metastasis development, therefore, implying that only surgery should be viewed as the tool for managing the disease, and that no further interventions, such as chemotherapy, will be obligatory in the identified scenario (The tumour trail left in blood, 2016).

Determining the degree to which a tumor has progressed in a particular child patient is an extremely complicated task, which the TEE may help resolve; however, for this purpose, the tool will have to be perfected so that more accurate results could be delivered in the process (The tumour trail left in blood, 2016).

Biomarkers identification

As stressed above, exosomes are viewed as the potential biomarkers in determining the presence and stage of cancer in child patients. The reasons for the choice of the said framework are quite basic. Seeing that exosomes take active part in the cell-to-cell communication process, it will be reasonable to assume that the said elements are bound to help in determining the presence of cancer in patients.

A closer look at the way in which the procedure works will show that the presence of DNA packages in exosomes is viewed as the means of differentiating between regular and cancerous exosomes. Seeing that the former typically have either very few DNA packages or none at all in them, whereas the latter have a substantial number of the said DNA packages, a close analysis of the exosomes present in the patient’s blood will help figure out whether cancer can be diagnosed in the identified scenario (The tumour trail left in blood, 2016).

Furthermore, the amount of proteins that are present in exosomes should also be considered the means of identifying the presence of cancer in young patients. Seeing that regular exosomes have very few proteins in them, whereas cancerous ones possess a significant amount thereof, a scrutiny thereof will also shed light on the current stage of cancer development in patients. Consequently, the use of the said biomarkers can be considered one of the most successful solutions to the problem of testing child patients for cancer. Particularly, the suggested framework implies that the MicroRNA (miRNA) expression should be scrutinized closely in the target cells so that cancer and the stage to which it has developed by the time that the test is taken could be identified.

The use of the identified elements as biomarkers makes the TEE tool extremely sensitive, therefore, allowing for a fast and efficient identification of the problem. Unlike other tests, which do not provide enough material to work with, the TEE framework allows for the identification of exosomes immediately and with a significant amount of precision. As a result, the prerequisites for a detailed introspect into the stages of cancer development can be created.

TEE and Child Cancer

As stressed above, the current framework does not allow for the levels of precision that will help identify the degree of metastasis in child patients. That being said, the TEE approach has the potential that needs to be explored further so that new opportunities could be discovered. The tool allows for a rather successful process of determining the differences between the DNA structures of exosomes; for instance, a recent study claimed that “conflicting observations suggest that exosomes and microvesicles may vary in DNA cargo composition” (Thakur et al., 2014).

In other words, the opportunities for identifying the composition of the DNA structures in exosomes have been created, and researchers are only a few steps away from determining the framework for a more careful and insightful analysis of the DNA composition. Thus, the basis for an accurate identification of the metastasis stage at which the patient currently is can be provided, with the further chances for diagnosing the problem precisely and designing the intervention that will meet the patients’ needs exactly. As a result, the instances in which invasive cancer therapy may not be required will be easier to identify; consequently, child patients will be exposed to a significantly smaller number of threats associated with the treatment process.

It should also be borne in mind that exosomally transferred miRNAs allow for the change in the behavior of stromal cells. Consequently, these miRNAs can be used to identify cancer cells. Nevertheless, the current lack of information about ex- miRNAs prevents researchers from determining the ways in which the tool can be useful in predicting cancer metastasis in children. The application of the TEE framework will require the use of tumor-related pathways, which play a huge role in the delivery and transfer of the signals that exosomes send to local and distant cells.

As soon as exosomes trigger the activation of fibroblasts, the microenvironment in which the said process occurs is altered slightly yet inevitably; as a result, the prerequisites for the rapid development of invasive cancer is created. The ability of the exosomes in question to inhibit the work of the immune system and, therefore, prevent the natural response to the production of the mutated cells, in turn, is an even more dangerous phenomenon that leads to the rapid growth of very aggressive cancer. Therefore, the identification of the pre-metastatic niche that exosomes create when the said process is launched is critical to the further successful management of the disease and the identification of the stage at which the patient currently is.

At this point, the technique known as the microfluidic technology deserves to be mentioned. Implying that the analysis should be carried out at the micro level, the said approach can be characterized by significantly higher precision levels. Consequently, the chances for detecting the presence of cancer and determining the stage to which its metastasis has evolved become increasingly easier. Recent research indicates that the specified approach has a huge potential as the tool for determining the cancer metastasis and creating forecasts for the patient:

This is a rapid (~100 min), readily scalable technique that employs much smaller samples than other approaches (~1/100 the amounts used in conventional methods). Its one-step isolation system eliminates multiple preparation steps, saving time and reagent costs. The potential for high specificity for exosome isolation will also enable the selection of subpopulations of exosomes by targeting both exosomal markers and tumour-associated markers (such as EpCAM, α-IGF-1R and CA125). (Thind & Wilson, 2016, p. 4)

The opportunity to develop a full-scale analysis based on a significantly smaller amount of exosomes can be deemed as a rather promising innovation, which is bound to have a significantly positive impact on children’s well-being in managing child cancer.

Conclusion

Child cancer remains a topical global issue for healthcare experts. Because of the lack of opportunities for predicting the emergence and development of cancer, death tolls remain dangerously high. However, an innovative approach toward testing patients for cancer metastasis may become the foundation for a significant improvement in the quality of care, as well as the rapid growth in the number of successful patient outcomes. Based on the analysis of the information transferred by exosomes and containing the elements of the miRNAs that are viewed as cancer biomarkers, the approach known as the tumor exosomes examination (TEE) creates prerequisites for carrying out a much more accurate analysis and, therefore, determining the stage of the cancer metastasis more precisely.

Creating the environment in which the tests for child cancer can be carried out in a much more efficient and accurate manner is a crucial step toward a significant improvement in patient outcomes and the overall quality of care. However, the current state of research regarding the application of the TEE framework is only in its first stages of development. Therefore, a further study of the subject matter is required so that the issue of child cancer could be addressed in a more efficient manner.

The significance of exploring the TEE-based strategy is truly ample. The framework offers the chances to increase the precision of the tests and, therefore, create the environment in which the metastasis can be prevented successfully, whereas cancer can be managed with the help of appropriate tools. However, apart from the identified opportunities, the innovative TEE approach allows for reducing the unpleasant experiences that patients have during the biopsy process.

The identified characteristic of the TEE tool is especially important for meeting the needs of children, who may develop anxiety, stress, and other comorbid mental health issues due to the harshness of the healthcare environment and the painful experiences such as biopsy. Thus, further promotion of the studies of the TEE-based approach to determining cancer metastasis in young patients (particularly, children) must be viewed as a necessity.

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