What are the other Names for this Condition? (Also known as/Synonyms)

• Diffuse Large B-Cell Lymphoma, Not Otherwise Specified
• DLBCL, NOS
• Non-Hodgkin's Lymphoma, Diffuse Large B-Cell type

What is Diffuse Large B-Cell Lymphoma, NOS? (Definition/Background Information)

• Diffuse Large B-Cell Lymphoma, NOS (or DLBCL, NOS) is a type of non-Hodgkin lymphoma, a cancer originating in the lymphatic system. DLBCL is one of the most common types of lymphoma in adults, accounting for about 30% to 40% of all cases
• It primarily affects B-cells, a white blood cell type responsible for producing antibodies to fight infections. The term "NOS" stands for "Not Otherwise Specified," indicating that DLBCL, NOS is a subtype of DLBCL that does not fit into more specific categories based on genetic or molecular characteristics. This subtype is diagnosed based on the appearance of the cancer cells under a microscope and other clinical factors
• Certain risk factors, including genetic predispositions, compromised immune function, previous exposure to certain viruses (such as Epstein-Barr virus and HIV), and environmental factors, may increase the likelihood of developing this lymphoma subtype. However, the exact cause of Diffuse Large B-Cell Lymphoma, NOS remains unclear, and it can develop in individuals without identifiable risk factors
• Diffuse Large B-Cell Lymphoma, NOS, is characterized by rapidly growing tumors that can occur in lymph nodes, organs, or other lymphatic tissues throughout the body. Depending on the location and extent of the disease, it can present with various symptoms, such as enlarged lymph nodes, fever, night sweats, weight loss, fatigue, and potential organ dysfunction
• The treatment for Diffuse Large B-Cell Lymphoma, NOS, typically involves chemotherapy, sometimes combined with immunotherapy or targeted therapy, depending on the individual's specific circumstances and the stage of the disease. The prognosis can vary widely depending on factors such as the patient's age, overall health, tumor size, and response to treatment

Who gets Diffuse Large B-Cell Lymphoma, NOS? (Age and Sex Distribution)

Diffuse Large B-Cell Lymphoma, NOS (DLBCL, NOS) can affect individuals of various ages and both sexes. However, certain age groups and demographics have a higher incidence of this type of lymphoma.

• It is most commonly diagnosed in adults, with the median age at diagnosis being around 60. DLBCL is more prevalent in older adults, and the incidence tends to increase with advancing age
• However, it can occur in individuals of any age, including children and young adults
• DLBCL, NOS affects both males and females, and there is no significant predilection for any one sex. Both genders have a relatively equal likelihood of developing this lymphoma type
• Worldwide, individuals of all racial groups and ethnicities are prone to developing this malignancy

What are the Risk Factors for Diffuse Large B-Cell Lymphoma, NOS (DLBCL, NOS)? (Predisposing Factors)

Diffuse Large B-Cell Lymphoma, NOS (DLBCL, NOS) is a complex disease with various potential risk factors that may contribute to its development. While the exact cause of DLBCL, NOS remains unclear in many cases, several predisposing factors have been identified, including:

• Age: Advancing age is a significant risk factor for DLBCL, NOS, with the median age at diagnosis typically around 60 years old. The incidence of DLBCL increases with age, and older adults are more likely to develop this lymphoma subtype
• Immune system compromise: Individuals with weakened immune systems due to conditions such as HIV/AIDS, autoimmune disorders, organ transplantation (and subsequent immunosuppressive therapy), or congenital immunodeficiencies are at an increased risk of developing DLBCL. A compromised immune system may fail to recognize and eliminate abnormal cells, allowing lymphoma cells to proliferate
• Previous lymphoma or cancer treatment: Individuals who have undergone certain types of chemotherapy or radiation therapy for previous cancers may have an increased risk of developing DLBCL as a secondary cancer. However, it is important to note that not all cancer treatments necessarily lead to DLBCL, and the risk varies depending on the specific treatments received
• Viral infections: Some viral infections have been linked to an increased risk of DLBCL. For example, Epstein-Barr virus (EBV) infection, especially in the setting of immunosuppression, is associated with a higher risk of developing DLBCL. Additionally, other viruses, such as hepatitis C virus (HCV) and human herpesvirus 8 (HHV-8), have been implicated in certain cases of DLBCL
• Genetic factors: While most cases of DLBCL, NOS are sporadic (occurring without a clear genetic predisposition), some genetic factors and gene mutations may play a role in increasing the risk of developing this lymphoma subtype. Research is ongoing to understand better the genetic basis of DLBCL and its potential implications for risk assessment and targeted therapies

It is important to remember that individuals without identifiable risk factors can still develop this lymphoma type, highlighting the multifactorial nature of its pathogenesis.

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one's chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes Diffuse Large B-Cell Lymphoma, NOS? (Etiology)

The exact causes of Diffuse Large B-Cell Lymphoma, NOS (DLBCL, NOS) are not fully understood, as the disease often develops due to a complex interplay of genetic, environmental, and immunological factors. However, several potential etiological factors have been identified that may contribute to the development of DLBCL, such as:

• Genetic abnormalities: DLBCL can arise from genetic mutations or abnormalities that affect the B-cells, leading to uncontrolled growth and proliferation. These genetic alterations can occur spontaneously or may be inherited, although inherited genetic factors are less common in DLBCL than in other types of lymphomas
• Immune system dysfunction: Dysfunction in the immune system can predispose individuals to DLBCL. Conditions that weaken the immune system, such as immunodeficiency disorders, autoimmune diseases, and long-term immunosuppressive therapies (e.g., after organ transplantation), can increase the risk of developing lymphomas like DLBCL
• Viral infections: Certain viral infections have been linked to an increased risk of DLBCL. For example, Epstein-Barr virus (EBV), known to infect B cells, is associated with a subset of DLBCL cases, particularly in immunocompromised individuals. Other viruses, such as hepatitis C virus (HCV) and human herpesvirus 8 (HHV-8), have also been implicated in DLBCL development in some cases
• Environmental exposures: Exposure to certain environmental factors or toxins may play a role in DLBCL development, although specific causative agents have not been definitively identified. Possible environmental factors include pesticides, industrial chemicals, and radiation exposure, but more research is needed to establish clear associations
• Chronic inflammation: Prolonged inflammation within the body, often associated with chronic infections or autoimmune conditions, can contribute to cellular changes and DNA damage that may increase the risk of DLBCL and other lymphomas
• Age: Advanced age is a significant risk factor for DLBCL, with the disease being more common in older adults

It is important to note that DLBCL, NOS is a heterogeneous disease, and not all cases have identifiable causes or risk factors. Research into the etiology of DLBCL is ongoing, focusing on understanding the molecular mechanisms underlying its development and identifying potential therapeutic targets.

What are the Signs and Symptoms of Diffuse Large B-Cell Lymphoma, NOS?

Diffuse Large B-Cell Lymphoma, NOS (DLBCL, NOS) can manifest with a range of signs and symptoms, depending on the location and extent of the lymphoma and individual factors such as overall health and immune function. 

The common signs and symptoms of DLBCL, NOS include:

• Enlarged lymph nodes: One of the primary manifestations of DLBCL is the enlargement of lymph nodes, which is often painless and can be felt in areas such as the neck, armpits, or groin. These swollen lymph nodes may be the first noticeable sign of the disease
• B symptoms:  B symptoms are systemic symptoms that may indicate more aggressive lymphoma activity. These include:
  • Fever: Persistent, unexplained fevers that may come and go or be continuous
  • Night sweats: Profuse sweating, especially at night, that may soak through clothing and bedding
  • Unintentional weight loss: Significant weight loss that occurs without dieting or exercise
• Fatigue: Persistent and unexplained fatigue or weakness that does not improve with rest or adequate sleep
• Abdominal pain or swelling: DLBCL can affect abdominal organs, leading to discomfort, pain, or swelling
• Chest pain or breathing difficulties: If DLBCL affects the chest or mediastinum (area between the lungs), it may cause chest pain, pressure, or difficulty breathing
• Neurological symptoms: In rare cases, DLBCL can involve the central nervous system (CNS), leading to symptoms such as headaches, seizures, changes in mental status, or neurological deficits
• Skin lesions: DLBCL can sometimes present with skin involvement, causing nodules, ulcers, or rash-like lesions

Additional signs and symptoms may include frequent infections, night-time itching (pruritus), bone pain, and general malaise.

It is important to note that not everyone with DLBCL will experience all of these symptoms, and some individuals may have few or no symptoms initially. Additionally, these symptoms can overlap with those of other medical conditions, making diagnosis based solely on symptoms challenging.

How is Diffuse Large B-Cell Lymphoma, NOS Diagnosed?

The diagnosis of Diffuse Large B-Cell Lymphoma, NOS (DLBCL, NOS) typically involves a comprehensive approach that combines various diagnostic tests and procedures. The process aims to confirm the presence of lymphoma, determine the subtype, assess the extent of the disease (staging), and gather information to guide treatment decisions.

The key steps in the diagnosis of DLBCL, NOS can include:

• Medical history and physical examination: The healthcare provider begins by taking a detailed medical history, including symptoms, previous medical conditions, family history, and potential risk factors. A thorough physical examination is also conducted to assess for signs such as enlarged lymph nodes, organ enlargement, or other abnormalities
• Blood tests: Blood tests, including a complete blood count (CBC) test and comprehensive metabolic panel (CMP), may be performed to evaluate overall health, assess blood cell counts, and check organ function
• Imaging studies: Imaging tests such as computed tomography (CT) scans, positron emission tomography (PET) scans, magnetic resonance imaging (MRI) scans, and/or ultrasound scans may be used to visualize internal organs, lymph nodes, and other structures. These imaging studies help determine the extent of lymphoma involvement and aid in staging the disease
• Biopsy: A tissue biopsy is the gold standard for diagnosing DLBCL. During a biopsy, a sample of abnormal tissue (such as an enlarged lymph node, organ tissue, or skin lesion) is removed and examined under a microscope by a pathologist. The biopsy helps confirm the presence of lymphoma, identify the specific type or subtype, and assess characteristics such as cell size, shape, and molecular markers
• Immunophenotyping: Immunophenotyping is a laboratory technique that uses special markers (antibodies) to identify and characterize specific types of cells, including lymphoma cells. This test helps classify the lymphoma subtype based on the expression of certain proteins on the cell surface
• Molecular testing: Molecular tests, such as fluorescence in situ hybridization (FISH), polymerase chain reaction (PCR), and next-generation sequencing (NGS), may be performed to detect specific genetic abnormalities or mutations in lymphoma cells. These tests provide valuable information about disease prognosis, potential treatment options, and minimal residual disease monitoring
• Bone marrow biopsy: In some cases, a bone marrow biopsy may be recommended to assess for lymphoma involvement in the bone marrow. This procedure involves taking a small sample of bone marrow tissue from the hipbone or sternum and examining it for abnormal cells
• Staging: Once the diagnosis of DLBCL, NOS is confirmed, staging tests are conducted to determine the extent of the disease and its spread to other parts of the body. Staging helps classify the lymphoma into stages (I to IV) and guides treatment planning.

The combination of these diagnostic tests and procedures allows healthcare providers to diagnose DLBCL, NOS accurately, determine the stage of the disease, and develop an individualized treatment plan tailored to the patient's specific condition and needs.

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible complications of Diffuse Large B-Cell Lymphoma, NOS?

Diffuse Large B-Cell Lymphoma, NOS (DLBCL, NOS) can lead to several potential complications, some of which may arise due to the characteristics of the lymphoma itself or as a result of its treatment. These complications can vary in severity and may require additional medical management. Some possible complications of DLBCL, NOS include:

• Tumor-related complications: DLBCL tumors can grow rapidly and infiltrate surrounding tissues or organs, leading to various complications depending on their location. For example, tumors near vital organs such as the brain, spinal cord, heart, or lungs can cause neurological symptoms, cardiac abnormalities, or respiratory issues
• Obstruction and compression: Large DLBCL tumors can obstruct blood vessels, lymphatic vessels, or other structures, causing venous or lymphatic obstruction, compression of nearby organs, or impaired circulation
• Systemic symptoms: B symptoms such as fever, night sweats, and weight loss can significantly impact a person's quality of life and may require symptomatic management and supportive care
• Immune dysfunction: DLBCL can affect immune function, particularly in individuals with advanced disease or those undergoing aggressive treatments like chemotherapy. This can increase the risk of infections, delayed wound healing, and other immune-related complications
• Hematologic complications: DLBCL can lead to abnormalities in blood cell counts, including low red blood cells (anemia), low white blood cells (neutropenia), and low platelets (thrombocytopenia). These hematologic complications can increase the risk of bleeding, infections, and fatigue
• Treatment-related complications: The treatments used for DLBCL, such as chemotherapy, immunotherapy, and radiation therapy, can cause various side effects and complications. These may include nausea and vomiting, hair loss, fatigue, immunosuppression, increased risk of infections, neuropathy, cardiac toxicity, secondary cancers, and fertility issues
• Psychosocial impact: Dealing with a cancer diagnosis and undergoing treatment for DLBCL can have significant psychosocial effects, including anxiety, depression, stress, and changes in mood or body image. Patients need to receive emotional support and access to resources for coping with these challenges
• Recurrence: Despite successful initial treatment, DLBCL can sometimes recur (return). Recurrence may require additional treatments and ongoing monitoring to manage the disease effectively

It is important for individuals with DLBCL, NOS to work closely with their healthcare team to monitor for potential complications, receive appropriate treatments and supportive care, and address any concerns or symptoms promptly. Early detection and management of complications can help improve outcomes and quality of life for patients with DLBCL.

How is Diffuse Large B-Cell Lymphoma, NOS Treated?

Diffuse Large B-Cell Lymphoma, NOS (DLBCL, NOS) is treated using a combination of therapies to control the disease, eliminate cancerous cells, and improve overall outcomes. The specific treatment approach for DLBCL, NOS may vary depending on factors such as the patient's age, overall health, disease stage, genetic characteristics of the lymphoma, and other individual considerations. 

The treatments options include:

• Chemotherapy: Chemotherapy is the primary treatment for DLBCL, NOS and involves using powerful anti-cancer drugs to kill cancer cells or inhibit their growth. The most commonly used chemotherapy regimen for DLBCL is called R-CHOP, which combines several drugs
  • R (Rituximab): A monoclonal antibody that targets and destroys B cells, including lymphoma cells
  • C (Cyclophosphamide): A chemotherapy drug that interferes with cell DNA replication, leading to cancer cell death
  • H (Doxorubicin, also known as Hydroxydaunorubicin): A chemotherapy drug that disrupts cancer cell division and growth
  • O (Vincristine, also known as Oncovin): A chemotherapy drug that inhibits cell division by disrupting microtubule formation
  • P (Prednisone): A corticosteroid that helps reduce inflammation and suppresses the immune response
• Immunotherapy: In addition to chemotherapy, immunotherapy with monoclonal antibodies such as Rituximab may be used as part of the treatment regimen. Rituximab specifically targets CD20 proteins found in the B cells, including lymphoma cells, and helps the immune system recognize and eliminate these cells
• Targeted therapy: Targeted therapy drugs may be used in certain cases, particularly for DLBCL subtypes with specific genetic mutations or alterations. These drugs target specific molecules or pathways involved in cancer cell growth and survival, such as Bruton's tyrosine kinase (BTK) inhibitors, PI3K inhibitors, and BCL-2 inhibitors
• Radiation therapy: Radiation therapy may be used in localized cases of DLBCL to target and shrink tumors in specific areas. It involves using high-energy beams to kill cancer cells and is often combined with chemotherapy for optimal results
• Stem cell transplantation: In some cases, particularly for younger patients with high-risk or relapsed/refractory DLBCL, autologous stem cell transplantation (ASCT) may be considered. ASCT involves harvesting the patient's healthy stem cells, administering high-dose chemotherapy to eliminate cancerous cells, and then reinfusing the stem cells to rebuild the bone marrow and immune system
• Clinical trials: Patients may also have the option to participate in clinical trials investigating novel treatments, new drug combinations, immunotherapies, or targeted therapies. Clinical trials offer access to cutting-edge treatments and may benefit treatment response and outcomes
• Supportive care and survivorship: Supportive care plays a crucial role in DLBCL management, addressing the physical, emotional, and psychosocial needs of patients throughout their treatment journey. This includes symptom management, nutritional support, pain management, psychosocial counseling, fertility preservation, and survivorship care planning to promote optimal well-being and quality of life

Treatment decisions for DLBCL, NOS are made collaboratively between the patient and their healthcare team, considering disease characteristics, treatment goals, potential side effects, and the patient's preferences and overall well-being. Regular monitoring, follow-up evaluations, and supportive care are essential components of DLBCL management to optimize treatment outcomes and quality of life.

How can Diffuse Large B-Cell Lymphoma, NOS be Prevented?

Preventing Diffuse Large B-Cell Lymphoma, NOS (DLBCL, NOS) is challenging because the exact causes are not fully understood. However, general strategies and lifestyle choices may help reduce the overall risk of developing lymphomas and other cancers, including:

• Maintain a healthy lifestyle: Adopting a healthy lifestyle can help support overall well-being and reduce the risk of cancer, which includes:
  • Eating a balanced diet rich in fruits, vegetables, whole grains, and lean proteins while limiting processed foods, red meat, and sugary beverages
  • Maintaining a healthy weight through regular exercise and physical activity
  • Avoiding tobacco products and excessive alcohol consumption
  • Protecting against infections by practicing good hygiene, getting recommended vaccinations (e.g., against hepatitis B and HPV), and taking precautions to prevent exposure to viruses associated with lymphomas, such as Epstein-Barr virus (EBV)
• Regular medical check-ups: Regular medical check-ups and screenings can help detect early signs of cancer or other health conditions. It is important to follow the healthcare provider's recommendations for age-appropriate cancer screenings, such as mammograms, colonoscopies, and Pap smears
• Manage chronic conditions: Proper management of chronic health conditions, such as autoimmune disorders or immunodeficiency conditions, can help reduce the risk of lymphomas like DLBCL. It is important to follow the healthcare provider's treatment plan and recommendations for managing these conditions effectively
• Avoid environmental toxins: Minimize exposure to environmental toxins and carcinogens whenever possible. This may include reducing pesticide exposure, industrial chemicals, pollutants, and radiation
• Sun protection: To reduce the risk of skin cancers, including cutaneous T-cell lymphomas, protect one’s skin from excessive sun exposure. Use sunscreen with a high SPF, wear protective clothing, and seek shade during peak sunlight hours
• Genetic counseling: Individuals with a family history of lymphomas or other cancers may benefit from genetic counseling and testing. Understanding genetic risk factors can help guide preventive strategies and early detection efforts
• Stay informed: Stay informed about cancer prevention, risk factors, and early warning signs. Educating oneself about lymphomas and other types of cancer can help one make informed decisions about one’s health and well-being

While these preventive measures can contribute to overall health and reduce cancer risk, it is essential to remember that not all cases of DLBCL, NOS can be prevented. Some risk factors, such as genetic predispositions or certain environmental exposures, may be beyond individual control. Therefore, maintaining a proactive approach to health, regular screenings, and early detection remain crucial components of cancer prevention and management.

What is the Prognosis of   Diffuse Large B-Cell Lymphoma, NOS? (Outcomes/Resolutions)

The prognosis of Diffuse Large B-Cell Lymphoma, NOS (DLBCL, NOS) can vary widely depending on several factors, including the patient's age, overall health, disease stage, specific characteristics of the lymphoma cells, response to treatment, and other individual considerations. DLBCL is considered an aggressive type of non-Hodgkin lymphoma, and prompt diagnosis and timely initiation of appropriate treatment are crucial for achieving favorable outcomes.

Some key factors regarding the prognosis and potential outcomes of DLBCL, NOS include:

• Response to treatment: DLBCL, NOS is generally responsive to treatment, particularly with standard chemotherapy regimens such as R-CHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone). Many patients experience a significant reduction in tumor size and may achieve complete remission (absence of detectable cancer cells) following initial treatment
• Prognostic factors: Various prognostic factors can influence the overall prognosis of DLBCL, NOS, including:
  • Age: Younger individuals have better outcomes than older adults
  • International Prognostic Index (IPI): The IPI score, based on factors such as age, disease stage, LDH levels, performance status, and the number of extranodal sites involved, helps stratify patients into risk categories (low, intermediate, high) and predict prognosis
  • Molecular and genetic characteristics: Specific genetic abnormalities or molecular markers in lymphoma cells can impact prognosis and guide treatment decisions. For example, MYC and BCL-2/BCL-6 rearrangements, TP53 mutations, and certain gene expression profiles may be associated with poorer outcomes
  • Response to initial treatment: Patients who achieve a complete or partial response to initial treatment generally have better long-term outcomes than those with refractory disease or relapse
• Survival rates: Overall, the prognosis for DLBCL, NOS has improved significantly with advances in treatment and supportive care. The 5-year survival rate for DLBCL ranges from approximately 60-70%, meaning many patients achieve long-term remission or cure. However, survival rates vary widely depending on individual factors and disease characteristics
• Relapse and refractory disease: Despite initial response to treatment, some patients may experience disease relapse (return of lymphoma) or have refractory disease (no response to treatment). In such cases, additional treatment options, including salvage chemotherapy, stem cell transplantation, targeted therapies, and participation in clinical trials, may be considered to manage the disease effectively
• Long-term follow-up: Patients with DLBCL, NOS require long-term monitoring and follow-up care even after achieving remission. Regular check-ups, imaging studies, and laboratory tests are essential for detecting any signs of disease recurrence or late effects of treatment, and addressing any ongoing health needs or concerns

Overall, the prognosis of Diffuse Large B-Cell Lymphoma, NOS has improved over the years due to advances in treatment strategies, including the incorporation of immunotherapy, targeted therapies, and personalized medicine approaches. Early diagnosis, appropriate risk stratification, multidisciplinary care, and ongoing research efforts are key components of optimizing outcomes and enhancing the quality of life for individuals with DLBCL, NOS.

Additional and Relevant Useful Information for Diffuse Large B-Cell Lymphoma, NOS:

While DLBCL, NOS is a common subtype of DLBCL, several other (distinct) subtypes of DLBCL have varying clinical and molecular characteristics. These include:

• Germinal center B-cell-like (GCB) DLBCL
• Activated B-cell-like (ABC) DLBCL
• Double-hit DLBCL (with MYC and BCL2/BCL6 rearrangements)
• Primary mediastinal large B-cell lymphoma (PMBCL)
• T-cell/histiocyte-rich large B-cell lymphoma
• EBV-positive DLBCL, NOS
• Primary cutaneous DLBCL, NOS

Molecular profiling: Advances in molecular profiling techniques, such as gene expression profiling (GEP) and next-generation sequencing (NGS), have enhanced understanding of DLBCL biology and led to the identification of specific genetic alterations and molecular subtypes. Molecular profiling helps guide treatment decisions, predict prognosis, and identify potential therapeutic targets for personalized medicine approaches.

• Role of immunotherapy: Immunotherapy, particularly using immune checkpoint inhibitors and chimeric antigen receptor (CAR) T-cell therapy, has emerged as a promising treatment approach for relapsed/refractory DLBCL and high-risk cases. Immune checkpoint inhibitors, such as pembrolizumab and nivolumab, target PD-1/PD-L1 interactions to enhance the immune system's ability to recognize and attack cancer cells. CAR T-cell therapy involves genetically modifying a patient's T cells to target and destroy lymphoma cells expressing specific antigens, such as CD19
• Central nervous system (CNS) prophylaxis: DLBCL patients with certain risk factors, such as high-grade disease, involvement of specific extranodal sites (e.g., testes or paranasal sinuses), or elevated LDH levels, may be at increased risk of CNS relapse. CNS prophylaxis, which involves administering intrathecal chemotherapy or systemic therapy with drugs that penetrate the blood-brain barrier, may be considered to reduce the risk of CNS involvement
• Patient advocacy and resources: Patient advocacy organizations, such as the Lymphoma Research Foundation, Leukemia & Lymphoma Society, and Lymphoma Coalition, offer valuable resources, support services, educational materials, and community networks for patients, caregivers, and healthcare professionals involved in DLBCL care. These organizations advocate for research funding, raise awareness, and provide advocacy platforms to empower individuals affected by lymphomas.

By staying informed, fostering collaboration among healthcare providers, utilizing advanced diagnostic and treatment modalities, and addressing holistic patient care needs, the management of DLBCL, NOS continues to evolve, leading to improved outcomes and better quality of life for patients.