Lack of Toxicity in a Patient with Germline Tp53 Mutation Treated with Radiotherapy

Abstract

patient population are scarce because of concerns that normal cells with mutated TP53 are more sensitive to rt than are cells without TP53 mutations and that rt will induce new primary cancers in these (often young) patients. CASE DESCRIPTIONA 61-year-old woman who had been diagnosed with stage ib uterine leiomyosarcoma in 2000 and with stage T2N0 papillary thyroid cancer in 2001 was referred for consideration of palliative rt to a right upper quadrant abdominal metastasis from her leiomyosarcoma that caused occasional pain and intermittent small-bowel obstruction. The leiomyosarcoma had initially been treated with total abdominal hysterectomy and bilateral salpingo-oophorectomy followed by adjuvant pelvic rt using a 4-field box technique (45 Gy in 25 fractions). The thyroid cancer was managed with thyroidectomy and adjuvant radioactive iodine [0.75 mCi (27.75 MBq)].The patient had no evidence of recurrence until 2007, when she developed biopsy-proven metastatic leiomyosarcoma to the lungs, heart, bone, and upper abdomen (Figure 1). She was initiated on doxorubicin and ifosfamide, which was followed by gemcitabine in the subsequent 2 years. Follow-up computed tomography imaging 3 months after the 18th cycle of gemcitabine revealed a lytic lesion of her right proximal humerus, which was subsequently treated with palliative rt for pain (35.25 Gy in 15 fractions) in 2010.The patient underwent further chemotherapy on trial (phase iii, eribulin vs. dacarbazine; search for NCT01327885 at http://clinicaltrials.gov/) and received dacarbazine until her current admission. Since 2010, she has also undergone 3 bile stent procedures secondary to the enlarging right-sided upper abdominal mass, which, at the time of the current consultation, measured 18.0×18.0×9.4 cm (Figure 2).During the course of the patient's palliative rt to the humerus, her infant granddaughter was ABSTRACT Li-Fraumeni syndrome is an autosomal dominant disorder characterized by germline TP53 mutation and increased susceptibility to cancer. Despite certain in vitro findings and a theoretical rationale for patients with TP53 mutation to be more radiosensitive and more prone to developing radiotherapy (rt)-induced secondary malignancies, corresponding clinical data remain elusive. Here, we report the case of a woman with TP53 mutation who was treated with adjuvant pelvic rt for stage ib uterine leiomyosarcoma in 2000, with radioactive iodine for papillary thyroid cancer in 2001, and with palliative rt to the humerus in 2010 for metastatic uterine leiomyosarcoma. She has not developed any acute or late rt-related toxicity, nor any secondary malignancies, since her first rt treatment. The literature review describes the potential risks and benefits of using irradiation in patients with TP53 mutation.

p53 Modulates Radiosensitivity in Head and Neck Cancers—From Classic to Future Horizons

“…However, Wong et al report the lack of late side effects and a second radio-induced cancer for a heavily treated patient with three radiotherapy sequences for various cancers. The authors note the possible protective effect of the p53 mutation for irradiation-related toxicities [ 43 ].…”