EP826 - Rectal Cancer with Li-fraumeni syndrome: A clinical conundrum

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Purpose/Background: Li-Fraumeni syndrome (LFS) is a hereditary disorder characterized by a markedly increased risk of various neoplasms, including soft tissue and bone sarcomas, breast cancer, brain tumors, and adrenocortical carcinoma. The underlying genetic defect in LFS is a germline mutation in the p53 tumor-suppressor gene. While colorectal adenocarcinoma is relatively uncommon among LFS-associated tumors, individuals with LFS have nearly three times the risk of developing colorectal cancer compared to the general population. Despite this increased risk, the clinicopathological features of colorectal cancer in LFS are not well characterized, and management poses unique challenges. Standard treatments, such as radiation therapy and alkylating agents, are contraindicated due to the increased risk of inducing secondary malignancies in LFS patients. This case highlights the clinical dilemma of managing rectal cancer in a patient with Li-Fraumeni syndrome.

Methods/Interventions: We present the case of a 53-year-old female with Li-Fraumeni syndrome and a personal history of breast cancer, now diagnosed with synchronous T4 upper rectal and T3 N+ mid-rectal cancer. Standard total neoadjuvant chemoradiotherapy was not an option due to the increased risk of secondary cancers associated with radiation in LFS patients. Furthermore, the use of alkylating agents, such as platinum-based chemotherapies, was relatively contraindicated. Given the advanced nature of her disease, the treatment options were limited. The patient ultimately received six cycles of FOLFOX chemotherapy without radiation, followed by a low anterior resection with splenic flexure mobilization.

Results/Outcomes: The patient’s post-operative course was uneventful, and pathological examination revealed a pT3pN2aM0 rectal cancer with clear circumferential resection margins, though the tumor showed poor response to chemotherapy. Interestingly, the pathological features of the tumors differed—one was an adenocarcinoma with mucinous and signet ring cell features, while the other exhibited conventional adenocarcinoma morphology. At present, there are no plans for adjuvant therapy, and the patient is under close follow-up.

Conclusion/Discussion: This case underscores the complex and atypical approach required for managing rectal cancer in patients with Li-Fraumeni syndrome. It highlights the need for personalized treatment strategies that balance oncologic control with minimizing the risk of secondary malignancies, an essential consideration in this high-risk population.