Complete Pathologic Response to PARP Inhibitor Olaparib in a Patient with Stage IVB Recurrent Endometrioid Endometrial Adenocarcinoma.

Treatment for endometrial cancer is rapidly evolving with the increased use and integration of somatic tumor RNA sequencing in clinical practice. There is a paucity of data regarding PARP inhibition in endometrial cancer given that mutations in homologous recombination genes are rare, and currently no FDA approval exists. A 50-year-old gravida 1 para 1 woman with a diagnosis of stage IVB poorly differentiated endometrioid endometrial adenocarcinoma presented to our comprehensive cancer center. Following surgical staging, she was placed on adjuvant chemotherapy with carboplatin/paclitaxel which was held multiple times due to poor performance status and complications. CT scan of the abdomen and pelvis following cycles 3 of adjuvant chemotherapy showed recurrent progressive disease. She received one cycle of liposomal doxorubicin but discontinued it due to severe cutaneous toxicity. Based on the BRIP1 mutation identified, the patient was placed on compassionate use of Olaparib in January 2020. Imaging during this surveillance period showed a significant decrease in hepatic, peritoneal, and extraperitoneal metastases, and eventually the patient had a clinical complete response in a year. The most recent CT A/P in December 2022 showed no sites of active recurrent or metastatic disease in the abdomen or pelvis. We present a unique case of a patient with recurrent stage IVB poorly differentiated endometrioid endometrial adenocarcinoma with multiple somatic gene mutations including BRIP1, who had a pathologic complete response following compassionate use of Olaparib for 3 years. To our knowledge, this is the first reported case of high grade endometrioid endometrial cancer that has shown a pathologic complete response to a PARP inhibitor.

The impact of childhood cancer and its treatment on puberty and subsequent hypothalamic pituitary and gonadal function, in both boys and girls.

Childhood cancer survivors (CCS) are at an increased risk of endocrine disorders. Disorders of the hypothalamic-pituitary-gonadal (HPG) axis are a particular concern because of their impact on pubertal development and future fertility and may be of central (hypothalamic or pituitary damage) or primary (gonadal) origin. Hypogonadism may present as pubertal disorders during adolescence and subsequent infertility in adulthood but should be anticipated to ensure appropriate surveillance is in place to address these issues at an appropriate age. Those at risk of HPG axis dysfunction include those with tumours primarily affecting the hypothalamus, pituitary or gonads themselves or due to their treatment with surgery, radiotherapy and chemotherapy. CCS who have had cranial irradiation of more than 30 Gy are at risk of gonadotrophin deficiency. Those who have had gonadotoxic chemotherapy, especially alkylating agents or radiotherapy to the gonads are at risk of primary gonadal failure. HSCT survivors who have had chemotherapy and total body irradiation are at risk of primary gonadal failure but may also have gonadotrophin deficiency. Understanding those at risk is essential to appropriate counselling and long-term follow-up. This chapter gives an overview on the impact of childhood cancer and its treatment on puberty, gonadal function and fertility in childhood cancer survivors.