Cancer Surveillance in Li-Fraumeni Syndrome: Challenges and Strategies

Introduction

Cancer surveillance or screening involves regularly monitoring individuals at a high risk of developing cancer or those with high-risk factors for its development. This cancer surveillance can aid in detecting cancers early, which is more treatable and can lead to better outcomes. Individuals with Li-Fraumeni syndrome have a 30 percent risk of developing cancer by the age of 30 years and a 90 percent risk by the age of 60 years. Advances in genetic testing can assist in identifying this condition. However, recent studies have shown that whole-body scans can also play a role in detecting LFS, facilitating early management, and increasing the survival rate.

What Is Li-Fraumeni Syndrome?

It is a rare genetic disorder that increases the risk of developing cancer at an early age. Individuals affected by this condition have a 90 percent probability of developing cancer. This condition occurs due to a mutation in the TP53 gene (tumor protein 53), a type of tumor suppressor gene that regulates cell division and prevents the growth of abnormal cells. Changes in genetic composition can cause this condition. Individuals can develop various cancers, such as leukemia, lung, colon, breast, brain, or sarcomas (connective tissue cancer). This condition can be inherited since it is a genetic disorder, but some individuals may also have new mutations. Genetic testing can be a diagnostic method for identification. Management includes regular cancer screening and monitoring at an early stage.

What Are the Challenges and Strategies Associated with Cancer Surveillance in Li-Fraumeni Syndrome?

In the past, Li-Fraumeni syndrome was identified primarily based on clinical features. However, with the advent of genetic testing for the TP53 gene, identification has become more precise. Additionally, predicting risk is of paramount importance in making surveillance decisions. This prediction is aided by analyzing the gene type, as comprehensive risk assessment tools are not widely available. Since not all individuals can undergo testing for the TP53 gene, relying solely on family history is insufficient for predicting cancer risk. This is because other genetic changes or new mutations can also contribute. It is important to note that current risk assessment methods cannot fully consider gene interactions.

Challenges associated with cancer surveillance of Li-Fraumeni syndrome include:

• Diverse Cancer Spectrum: Individuals with Li-Fraumeni syndrome are at risk of developing multiple cancers, such as brain, blood, bone, breast, colon, or gastrointestinal cancers. This diversity makes it challenging to create a comprehensive surveillance strategy.

• Early Onset: Cancers associated with this syndrome tend to develop at a younger age, leading to distress for children, parents, and their families when considering early-age surveillance.

• Frequent Surveillance: Individuals with Li-Fraumeni syndrome require frequent and intensive screening methods, including MRI (magnetic resonance imaging), ultrasound, colonoscopy, and other tests. These screenings can be physically and emotionally taxing for the patient, potentially affecting their quality of life.

• False Negatives: Occasionally, non-cancerous growths might be mistakenly identified as cancer. However, additional tests can rectify these cases, ensuring accurate diagnosis. Such instances highlight that screening can yield unexpected findings, causing financial and emotional stress for families. Circulating tumor DNA (ctDNA) can help in reducing false positives.

• Extra Tests: As patients undergo whole-body MRI scans, unexpected findings can lead to extra tests, resulting in anxiety while awaiting the results.

• Emotional Impact: Screening can negatively affect the emotional well-being of both patients and their families. The period between a positive screening and a confirmatory test is often stressful. Even genetic results can induce stress.

• Exposure To Radiation: Surveillance methods like CT scans carry the risk of radiation-induced cancers.

Strategies associated with cancer surveillance in Li-Fraumeni Syndrome include:

• Early Initiation and Frequent Screening: Surveillance should commence early, aiding in the early-stage management of cancer and yielding positive outcomes. This approach should incorporate regular and frequent screening, encompassing imaging tests and physical exams.

• Multidisciplinary Care: Screening should involve a team of healthcare professionals, including genetic counselors, radiologists, oncologists, and psychologists.

• Long-Term and Regular Follow-Up: Surveillance should span the patient's entire life, consistently assessing results. Based on these assessments, lifestyle management should also be integrated, encompassing diet and exercise, contributing to the patient's overall well-being.

• Sick Kids Protocol: This protocol is applied to children with TP53 gene mutations. Its purpose is to assess the cancer risk in children. This involves yearly examinations encompassing growth monitoring, blood pressure checks, observation for changes in appearance due to increased cortisol (Cushingoid appearance), assessments of the nervous system, and identifying abnormal features such as virilization. Furthermore, regular medical examinations and imaging tests are performed.

Current recommendations consist of:

• Adrenocortical Carcinoma: Screening is conducted until the age of 18. This involves pelvic and abdominal ultrasounds, complete urine analysis, and blood tests for b-HCG (beta-human chorionic gonadotropin), AFP (alpha-fetoprotein), testosterone, and 17-OH-progesterone every three to four months.

• Brain Tumor: An annual MRI with contrast is recommended initially. If the initial MRI is normal, subsequent screenings can be performed using non-contrast MRI.

• Soft Tissue and Bone Sarcoma: A comprehensive body MRI should be performed annually.

• Leukemia or Lymphoma: Blood tests, including complete blood count, lactate dehydrogenase, and erythrocyte sedimentation rate, should be conducted every three to four months.

• Breast Cancer: For patients above 18 years old, this includes a clinical breast exam twice a year and a yearly breast MRI.

• Colon Cancer and Gastrointestinal Tract Malignancies: Endoscopy and colonoscopy should be performed every two to five years, starting from age 25 or earlier. If there is a history of colon cancer in the family, screening should be started ten years before the youngest case in the family.

• Melanoma: From age 8, yearly skin exams should be conducted.

Conclusion

Cancer surveillance plays a pivotal role in cancer prevention and early management. Detecting cancer in its early stages enhances treatment effectiveness, reduces aggressiveness, and improves outcomes and survival rates. Despite the challenges, early and regular screening and a multidisciplinary approach offer hope by identifying cancers at their nascent stages.