Factor XIII (FXIII) is a thrombin-activated protransglutaminase that plays a key role in blood clot formation. Congenital FXIII A-subunit deficiency represents a rare bleeding disorder that affects one in 2-3 million individuals worldwide and is treated with recombinant FXIII (rFXIII). However, due to the rarity of the disease, clinicians are often left to weigh individual variation in FXIII activity and/or symptoms to optimally guide dosing. Cases often become further complicated when patients experience refractory bleeding, which can be difficult to treat. This report describes an approach to rFXIII dosing in two patients who required deviation from standard protocols to maintain therapeutic FXIII troughs. We highlight limitations in our understanding of FXIII deficiency management, while also providing an example of the application of pharmacokinetic data to individualise therapy for improved outcomes. Finally, the case reminds us of the importance of patient-centered, cost-conscious care and multidisplinary teamwork in complex cases.
Abstract PURPOSE: Utilization of stereotactic radiosurgery (SRS) for brainstem metastases (BSM) is increasing. Multi-fraction SRS (MF-SRS) is a potential means of obtaining therapeutic gain while limiting toxicity. However, most available data assesses only single-fraction SRS (SF-SRS). This study aims to evaluate the efficacy and safety of SF-SRS and MF-SRS for BSM. METHODS: Data was retrospectively collected for patients with BSM treated with SRS between 2003–2018 at a single institution. Kaplan-Meier method was used to evaluate overall survival (OS) and local control (LC). Independent t-test was used for correlations between groups. RESULTS: 29 patients (31 lesions) were identified; 13 patients (15 lesions) underwent SF-SRS and 16 patients (16 lesions) underwent MF-SRS. Median follow-up was 6.8 months (1–80.8 months). Post-SRS MRI was available for 78% of patients. Median dose was 16Gy (12–18 Gy) for SF-SRS and 24 Gy (18–30 Gy) for MF-SRS. MF-SRS was delivered in a median of 3 fractions (3–5). There was a trend toward larger mean tumor volume with MF-SRS (1.297 vs 0.302mL, p=0.055). OS was 64.8% at 6 months and 49.3% at 12 months. LC was 90.9% at 6 months and 69.9% at 12 months. LC was similar between SF-SRS and MF-SRS at 6 months (100% vs 79.5%, p=0.143) and 12 months (50.0% vs 79.5%, p=0.812). Among the 4 patients who experienced local recurrence, 3 received salvage whole brain radiation and median OS was 8.1 months after LF. Distant CNS failures occurred in 40.3% of patients at 6 months and 72.4% at 12 months. Tumor volume >0.5 mL was associated with worse LC at 6 months (64.3% vs 100%, p=0.022). One patient developed symptomatic radiation necrosis (1/29 lesions, 3.4%) after MF-SRS. CONCLUSION: SRS is a safe and effective treatment for small BSM. Outcomes were not different between SF-SRS and MF-SRS but analysis is limited by small sample size.
Mixed gestational trophoblastic neoplasias (GTNs) are rare placental tumours that arise from abnormal fertilisation events. To date, only 34 patients with mixed GTNs have been reported in the literature. As such, the management of such cases remains challenging. This report presents a case of a mixed GTN that was further complicated by a synchronous primary lung adenocarcinoma. Our patient was initially treated with hysterectomy, with surveillance labwork showing persistence of her malignancy. She then began combination chemotherapy, at the end of which she appeared to be in remission clinically. Unfortunately, subsequent imaging showed the persistence of pulmonary nodules that were ultimately resected, demonstrating a new primary lung adenocarcinoma. At present, she remains free of both cancers 2 years after her initial diagnosis. The complexity of this case underscores the importance of patient-centred treatment for rare tumours and the role of a multidisciplinary team in the effort to provide holistic care.
