• PDF / 171,661 Bytes
• 1 Pages / 595.245 x 841.846 pts (A4) Page_size
• 27 Downloads / 164 Views

DOWNLOAD

REPORT

---

1 S

Hypermutation and grade 1 pruritis: case report A 37-year-old woman exhibited drug resistance due to hypermutation during treatment with temozolomide for cervical neuroendocrine neoplasm (NEN) and developed grade 1 pruritis during treatment with pembrolizumab [dosages, routes, times to reaction onsets and outcomes not stated]. The woman, who presented with atypical vaginal bleeding in 2013, was subsequently diagnosed with a 3.2-cm poorly differentiated high-grade cervical NEN (WHO grade 3). She underwent an R0 radical hysterectomy. She then underwent adjuvant cisplatin and etoposide with concurrent radiation lasting a combined 12 weeks. After a 7-month disease free interval, she developed an isolated hepatic recurrence. She underwent hepatic resection, which revealed a similar 1.3cm poorly differentiated high-grade neuroendocrine carcinoma (WHO grade 3). She then participated in a clinical trial of trametinib. She remained in the trial for 8 months before developing disease progression in the liver. Then, she underwent resection of a dominant liver lesion and laparoscopic microwave ablation of an additional segment 4A lesion. After surgery, she received carboplatin, paclitaxel and bevacizumab. She experienced disease progression in the liver after 11 months. She opted to participate in a clinical trial of a GITR immune checkpoint agonist antibody. However, she developed disease progression with new liver metastases after 3 months receiving therapy. Thus, she was taken off trial and transitioned to single-agent temozolomide [TMZ] on days 1-5 of a 28-day cycle. Two months after initiating temozolomide, imaging showed radiographic response. However, 7 months after initiating temozolomide, MRI and positron emission tomography (PET)-CT scanning showed an increase in known hepatic disease and a new left pelvic sidewall/ovarian mass. Capecitabine was added to temozolomide. However, she continued to experience disease progression and underwent palliative debulking of the left ovarian mass (ovarian resection) and hepatic wedge resection (focal hepatic microwave ablation). Histologic examination (liver and ovarian masses) showed similar poorly differentiated high-grade NEN with Ki67 80%-90%, with some areas of increased lymphocytic infiltrate. After operation, based on purported synergy observed in other tumour types, she opted for expanded access pembrolizumab in combination with bevacizumab. She achieved radiographic response in the known liver disease, followed by radiographic disease stability lasting >24 months. During treatment with pembrolizumab, she experienced grade 1 pruritis, likely related to pembrolizumab. After 26 months of pembrolizumab treatment, she developed disease progression with new pleural based lung lesions and an increase in hepatic disease. She then underwent commercial genomic profiling, which revealed the following: the initial tumour harbored pathogenic KRAS G12V and MAP3K1 alterations were preserved across all tumour samples, all pre-temozolomide samples were characterized by a low/ interme