DIAGNOSTICS AND MONITORING

Brain tumors include primary brain tumors and brain metastases.

Common primary brain tumors include gliomas, meningiomas, pituitary tumors, ependymomas, embryonal tumors, etc. Common brain metastases include lung cancer brain metastases, and breast cancer brain metastases, melanoma brain metastases, etc.

Genetic testing can provide brain tumor patients with molecular diagnostics & prognostic evaluation, screening for targeted immunotherapy drug solutions, assessments for chemotherapy sensitivity, optimizing targeted treatment plans for diagnosis while also providing a hereditary genetic risk profile.

Malignant liver tumors are divided into two main classifications: primary and secondary. Primary hepatic cancer has high incidence and mortality, due to the large population of hepatitis B patients in China. Liver cancer is mostly generated from post-hepatitic cirrhosis in hepatitis B and hepatitis C patients. Primary hepatic cancer has insidious onset, inconspicuous early symptoms, rapid progression, and high malignancy. Most of these diseases have already advanced when diagnosed, and the best window of time for treatment has passed, so the five-year survival rate is extremely low. At present, surgical resection is the main radical treatment for primary hepatic cancer, with a five-year survival rate of only about 50% and a five-year recurrence rate of 60%–70%. The clinical treatments for advanced primary liver cancer consist of mostly systemic drug therapy, including systemic chemotherapy, molecular targeted therapy, and immunotherapy. Pathological types of primary liver cancer include hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), and mixed type of HCC-CC. HCC is the most common (85%-90%), followed by ICC (10-15%), and the mixed type of HCC-CC is the least common. “Liver cancer” often refers to "hepatocellular carcinoma".

Hematological cancer are malignant tumors that occur in the blood system (bone marrow, hematopoietic and lymphatic tissues). The most common hematological tumors are various types of leukemia, multiple myeloma and malignant lymphoma.
Leukemia is the most common hematological tumor, caused by malignant transformation of white blood cells, and is classified as acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic myeloid leukemia/chronic myeloid leukemia (CML), chronic lymphocytic leukemia (CLL) and rare types of leukemia.
Multiple myeloma (MM) is a malignant plasma cell hematological tumor that occurs mainly in middle-aged and elderly people, MM incidence accounts for approximately 10% of hematological tumors ^[1], and is the second most common hematological malignancy after malignant lymphoma in many countries.
Treatment of hematological tumors generally include drug therapy, surgery, chemotherapy, immunotherapy and hematopoietic stem cell transplantation. After remission of hematological tumors, a small number of tumor cells remain in the body, which is the root cause of recurrence of the disease. Minimal Residual Disease (MRD) testing can provide early prediction of recurrence, stratify the patient's risk level, guide post-remission treatment, and determine the optimal time for bone marrow and stem cell transplantation. MRD testing includes four methods: Flow cytometry, quantitative RT-PCR of fusion genes, quantitative PCR of IgH/TCR rearrangements, and NGS sequencing. For hematological tumors such as multiple myeloma (MM), acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL), NCCN guidelines recommend the use of flow cytometry and NGS for MRD detection. ^{[2] [3] [4] [5]}

Gastrointestinal tumor are common malignant tumors in the digestive system, including gastric cancer, colon and rectal cancer. About 30% of gastric cancer patients in China have advanced gastric cancer with distant metastases, and their 5-year survival rate is less than 10%, while the survival rate of locally progressive gastric cancer is 13%-34% ^[1]. Gastric cancer can be divided into various types, among which adenocarcinoma is the most common, accounting for more than 90% ^[2]. The liver is the most observed target organ for hematogenous metastases ^[3].
At present, treatment of advanced gastric carcinoma includes systemic chemotherapy, surgical resection, radiation therapy, targeted therapy, and immunotherapy. Although the treatment methods are constantly optimized, the median survival times of patients is still less than a year. In addition, HER2 overexpression is detected in only about 16% of gastric adenocarcinoma patients^[4], and the use of first-line therapeutic targeted agents is low.
Colorectal cancer (colon cancer), is also a common malignant tumor in the digestive system, including colon and rectal cancer. The most common type of colorectal cancer is adenocarcinoma, which can metastasize through blood and lymphatic systems. The five-year survival rate of patients with early-stage colorectal cancer reaches 80%–90%^[5], but 50%–60% of the patients tend to already be in advanced stages when diagnosed^[6], with livers and lungs as common metastatic sites. Major treatments for colorectal cancer include targeted therapy, immunotherapy, and chemotherapy. Genetic testing provides guidance for medication selection and also provides genetic risk information. The testing of the following genes is recommended for colorectal cancer patients, under NCCN guidelines: KRAS/NRAS/BRAF/NTRK/HER2/MSI/MMR^[7].

Thyroid cancer is a malignant tumor that originates from the follicular or parafollicular epithelial cells of the thyroid glands, which is also the most common malignant tumor in the head and neck regions. In recent years, the incidence of thyroid cancer has increased rapidly worldwide. According to the National Center of Cancer Registry, the incidence of thyroid cancer ranks fourth in women in urban areas of China, among all malignant tumors in women. The number of thyroid cancer cases in China will continue to increase at a rate of 20% per year.
According to the tumor origin and differentiation, thyroid cancer is further classified into papillary thyroid carcinoma (PTC), follicular thyroid carcinoma (FTC), medullary thyroid carcinoma (MTC), and anaplastic thyroid cancer (ATC). PTC is the most common type of thyroid cancer, accounting for about 85%–90% of all thyroid cancers. PTC and FTC are collectively referred to as differentiated thyroid carcinoma (DTC). Different pathological types of thyroid cancer are characterized by significantly different pathogenesis, biological behaviors, histological morphology, clinical manifestations, treatment methods, and prognosis. DTC is mild in biological behaviors, with a better prognosis. ATC is of higher malignancy, with a median survival of only 7–10 months. The prognosis of MTC tends to be between those of the two types above.
For benign or malignant thyroid nodules that are not determined by fine needle aspiration biopsy (FNAB), a test can be performed on fine needle aspiration specimens for thyroid cancer molecular markers, such as BRAF mutations, Ras mutations, and RET/PTC rearrangements. This helps improve diagnosis accuracy. Detection of BRAF mutations in preoperative fine needle aspiration specimens is also conducive to the diagnosis and clinical prognosis prediction of PTC and the development of individualized diagnosis and treatments. The American Thyroid Association (ATA) recommends that all patients with MTC, even those with a significant tendency of sporadic MTC, should be tested for RET mutations.

Breast cancer is the most common type of malignant tumors in women, which seriously threatens women's health all over the world. In 2015, there were about 304,000 new cases of female breast cancer in China, with an incidence of 45.29/100,000 and about 70,000 deaths. Among new cases of breast cancer each year, about 3%–10% of women have distant metastases at the time of diagnosis. 30% of the early-stage cases can evolve into advanced breast cancer, and their five-year survival rate is only 20%. Advanced breast cancer is a special stage in breast cancer development and differs from other stages in both treatment and efficacy. Patients with advanced breast cancer face pressure from multiple aspects, including the disease itself, psychological factors, and related economic factors. About 20% of breast cancers are advanced locally, but free of distant metastases at first diagnosis. Before treatments, a needle biopsy should be performed to obtain the expression status of histological and biological markers, and gene mutations (e.g., PI3K and BRCA mutations) should be detected as soon as possible to assist with developing a treatment plan. The neoadjuvant therapy should be actively adopted for patients with locally advanced diseases that may transfer into a radical cure by surgery. For advanced breast cancers with HR-positive HER-2 negative, CDK4/6 inhibitors in combination with endocrine therapy can be selected preferentially for patients without visceral crisis. Chemotherapy may be considered for patients who are not suitable for endocrine therapy or have seen rapid disease progression after endocrine therapy. Endocrine therapy can be used as maintenance therapy after the disease is effectively controlled. Platinum chemotherapy is an important treatment option for patients with triple-negative breast cancer, patients with BRCA mutations have better efficacy. Therefore, BRCA gene tests are recommended, especially for younger patients. At present, only germline BRCA1/2 gene mutations in hereditary breast cancer are valuable for clinical application and treatment, so genetic tests should be performed as early as possible when targeted therapies are available. The NCCN guidelines recommend that the 21-gene test can be used for some hormone receptor-positive and HER2-negative patients.

Urothelial carcinoma refers to urothelial malignant tumors that occur in the renal pelvis, ureter, bladder, and urethra. Among these, bladder cancer accounts for about 90% of cases, with an incidence rate that ranks ninth worldwide, just following prostate cancer, amongst other urinary system tumors. It is also one of the most expensive tumors to treat^[1]. At present, there are still some concerns with the clinical treatment of bladder cancer in both early diagnosis and advanced treatment.
For early auxiliary diagnosis, the diagnoses and follow-up examinations of bladder cancer mainly rely on a combination of cystoscopies examination, imaging, and testing of urine exfoliated cells. However, cystoscopies are invasive and painful, risking infection and bleeding. Urine exfoliative cytology has good specificity but is extremely low in sensitivity, which can be easily disrupted by factors such as urinary tract infection. Also, for patients with painless hematuria in clinical practice, the presence of tumors cannot be determined by cystoscopies and imaging, and there is still no good supplementary means to assist physicians with judgment calls. Therefore, it has become the popular topic for research in recent years to seek noninvasive, highly sensitive, highly specific, simple and feasible tumor markers as the basis for diagnosis and follow-up examinations of urothelium carcinoma. At present, multiple gene mutations, combined with the gene methylation model can effectively identify benign and malignant bladder cancers at early stages^[2].
For advanced treatments, treatment of bladder cancer in China still consist of treatments based on systemic chemotherapy, surgical resection, radiation therapy, targeted therapy, and immunotherapy. In recent years, with the rise of immunotherapy, five types of PD1/PD-L1 inhibitors have been approved by the FDA as second-line therapies. Atezolizumab and pembrolizumab can be used as the first-line therapy for mUC(urothelium carcinoma), with no indicator for cis-platinum or with high PD-L1 expression^[3]; however, there has been no improvement in targeted therapies until April 2019, when Erdafitinib, the first targeting drug for bladder cancer, was finally approved and marketed in the United States. Since then, the treatments for bladder cancer has entered the era of precision therapy^[4].