VCOM Carolinas Research Day 2023

Clinical Case-Based Reports

INTRALESIONAL 5- FLUOROURACIL IN THE TREATMENT OF SQUAMOUS CELL CARCINOMA IN AN ELDERLY PATIENT Stephanie M. McDonald, B.S., OMS-II, Dr. Peter Neidenbach, MD, FAAD Edward Via College of Osteopathic Medicine-Carolinas, Spartanburg, South Carolina. Abstract Results Conclusion

Abstract # CBR-23

Figure 2: Pathology report: Squamous cell carcinoma, well-differentiated. The tumor is composed of nodular masses of neoplastic squamous cells with atypical nuclei, keratin pearl formation, and scattered mitotic figures, surrounding fibrosis and inflammation present.

Conclusion The gold standard of care in the treatment of squamous cell carcinoma is surgical removal. 2 This poses a problem in patients who are unable to tolerate surgery and/or the associated complications with surgery. Complications of surgery in an elderly patient or a patient with comorbidities include improper wound healing, the risk of infection, bleeding, and pain. The elderly population can benefit from intervention and treatment of SCC with IL5-FU. In this case, the woman was frail with thin skin and comorbidities. Patient was wheelchair bound and oxygen dependent, and thus, not considered a good surgical candidate. Due to the above presentation and comorbidities, the patient was also not considered a candidate for radiation. IL5-FU is an alternative treatment that can be used in patients who may not be good candidates for surgery. This could have posed improper healing of the wound created by surgical excision of the tumor especially on extremities where circulation may be reduced in comparison to the trunk of the body. With surgery comes risks including infection, bleeding, and pain. These stated risks were reduced via the minimally invasive injections of 5-FU in comparison to a more invasive surgery. There is low morbidity associated with this form of treatment as well as a low mortality rate. Surgery poses a problem in patients who are unable to tolerate the associated complications. Regarding cost, 5-FU is more inexpensive in comparison to surgery. Furthermore, IL5-FU can be used in areas where access to healthcare is limited such as rural areas. In this instance, the patient did not have to drive far for her care indicating a lower barrier to healthcare. This means that other physicians can potentially treat their patients using this form of treatment, especially in rural areas where access to a surgeon or surgical equipment is limited. Discussion Cutaneous squamous cell carcinoma tends to arise after UV exposure due to the DNA damage induced. 1 To prevent SCC, limiting sun exposure and wearing sunscreen of minimum of SPF 30 are essential to reduce one’s risk. SCC develops from malignant proliferation of the squamous cells in skin (keratinocytes). The precancerous lesion of SCC is actinic keratosis. Mutations in the tumor suppressor gene TP53 have been elucidated as an early event that occurs after sun exposure. 1 5-Flurouracil is a chemotherapy agent that works as an antimetabolite-pyrimidine analog that blocks thymidylate synthetase, this in turn blocks DNA synthesis. 3 This drug specifically is converted to fluorodeoxyuridine monophosphate (FdUMP) and this binds with thymidylate synthase to block the production of deoxythymidine monophosphate (dTMP) or thymidylate. dTMP is needed for DNA repair; 5- FU causes significant damage to dTMP’s ability to repair DNA. 3, 4 This agent is currently FDA approved for various cancers, but it has been particularly beneficial in the topical treatment of other dermatologic neoplasia like basal cell carcinoma and keratoacanthoma. 2, 5 In a case report by Thomas Vazquez, a 96-year-old man presented with a SCC on the leg and was treated with a similar method to our patient using a topical anesthesia with multiple injections of 5-FU 50mg/mL solution for 1.5mL in total. 6 Both patients saw complete regression of their tumors with the use of IL5-FU. However, it is to be noted, trichloroacetic acid (TCA) was also used in the 96-year-old patient. The use of TCA may pose as a confounding variable in studying the effect of IL5-FU. 6 A limitation of intralesional 5-FU is that it needs to be studied further in the treatment of SCC on the extremities in the elderly. Furthermore, it should not be used in those with metastasis of cancer. Guidelines currently do not mention or support the use of IL5-FU in the treatment of cutaneous SCC. 7 The guidelines mention use of topical, not intralesional, 5-FU in 2 different case series but this treatment is not yet supported based on lack of data. 7 A retrospective cohort study was conducted by identifying 148 patients with SCCs and the use of IL-5FU. 8 The volume varied from 0.2mL to 2mL for each lesion, indicating that this treatment option has not yet been standardized. 8 A randomized controlled trial should be conducted to compare surgery versus IL injection on many patients to determine if the IL injection is effective in all patients, or in what percentage.

Context: Squamous cell carcinoma is the second leading form of skin cancer 1 . In the elderly population, surgery may carry more risk and significant morbidity in comparison to less invasive forms of treatment. Report of Case: A 98-year-old woman presented in early May 2017, with a 3.5 cm rapidly growing crusted nodule on her left proximal-lateral arm. She had a history of chronic obstructive pulmonary disease, atrial fibrillation, and heart failure. Patient also had a frail body habitus and weighed 80 pounds. Physical examination revealed a large, ulcerated, crateriform mass on the left proximal lateral arm. A shave biopsy was performed which revealed a well-differentiated squamous cell carcinoma (SCC), composed of nodular masses of neoplastic squamous cells with atypical nuclei, keratin pearl formation, and scattered mitotic figures with surrounding fibrosis and inflammation. Patient was wheelchair bound and oxygen dependent, and thus, not considered a good surgical or radiation candidate. Diagnosis : Squamous cell carcinoma, well-differentiated. Methods : PubMed and the Journal of the American Academy of Dermatology were referenced for this report. The following keywords were searched: “intralesional 5 - flurouracil”, “5 - flurouracil in squamous cell carcinoma”, “5 -FU in squamous cell carcinoma”, “nonmelanoma skin cancer”, “nonmelanoma skin cancer treatment”, “Intralesional 5 -fu in the treatment of squamous cell carcinoma”, “skin cancer”, and “SCC”. Treatment: For treatment, the patient was prepped with 1 cc Triamcinolone (Kenalog) 40 mg/ml diluted to 3 cc with bupivacaine (Marcaine) 0.5% which was injected circumferentially. Following this injection, 1.5 cc of 5-fluorouracil (5-FU) 50mg/ml solution was injected peripherally into the buttress of the tumor. Subsequently, Aquaphor, Telfa and Coban wrap were applied and left on overnight. At follow up, the patient had a good response to therapy and there was no visible or palpable evidence of the tumor at 4 weeks. At 3 months there was no sign of recurrence. The patient later died due to unrelated causes in September 2017. Methods

Figure 3 . Follow up at 4 weeks status post intralesional 5-FU injection on left proximal, lateral arm.

References

Figure 4 . Result at 3 months. No lesion present status post intralesional 5-FU injection on left proximal, lateral arm.

Figure 1. Large ulcerated, crateriform mass on left proximal, lateral arm

Acknowledgements

None.

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