Response to sirolimus in capillary lymphatic venous malformations and associated syndromes: Impact on symptomatology,quality of life,and radiographic response

Background

Capillary lymphatic venous malformations (CLVM) and associated syndromes, including Klippel–Trenaunay syndrome (KTS) and congenital lipomatous overgrowth, vascular malformation, epidermal nevi, skeletal, and spinal syndrome (CLOVES), are underrecognized disorders associated with high morbidity from chronic pain, recurrent infections, bleeding, and clotting complications. The rarity of these disorders and heterogeneity of clinical presentations make large-scale randomized clinical drug trials challenging. Identification of PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [gene]) mutations in CLVM has made targeted medications, such as sirolimus, attractive treatment options. The aim of this study was to investigate the safety and efficacy of sirolimus therapy in CLVM.

Procedure

A combined prospective and retrospective cohort of pediatric and young adult patients with CLVM treated with sirolimus was evaluated for disease response, including symptom improvement, quality of life (QOL), and radiologic response. Sirolimus dosing regimens and toxicities were also assessed.

Results

Twenty-nine patients with CLVM, including KTS and CLOVES, were included. Ninety-three percent of patients reported improved QOL, and 86% had improvement in at least one symptom. Most significantly, improvement was noted in 100% of patients with bleeding and 89% with thrombotic complications with corresponding decreases in mean D-dimer (p = .008) and increases in mean fibrinogen (p = .016). No patients had progressive disease on sirolimus. Most common side effects included neutropenia, lymphopenia, infection, and aphthous ulcers/stomatitis. No toxicities were life-threatening, and none required long-term discontinuation of sirolimus.

Conclusion

Sirolimus appears to be effective at reducing complications and improving QOL in patients with CLVM and associated syndromes. In this patient cohort, sirolimus was well tolerated and resulted in few treatment-related toxicities.     

Trajectories of Psychological Distress in Australians Living in Urban Poverty: The Impact of Interpersonal Trauma

Childhood maltreatment and interpersonal trauma experience is an important factor underpinning the apparent perpetuation of the cycle of social disadvantage experienced by homeless adults. This paper aimed to examine longitudinal patterns of psychological distress in a sample of 1,504 socially disadvantaged adult participants from the Journeys Home Study in Australia. The current paper utilized the “conservation of resources” theory and the concept of “risk factor caravans” to investigate the nature and implications of childhood trauma in the context of homelessness. Growth mixture modeling revealed four distinct trajectories of psychological distress as measured by the Kessler 6 across six time points (covering a period of 2.5 years): chronic, escalating, attenuating, and resistant. Our results also indicated that experiences of different types of trauma during childhood were associated with these psychological distress trajectories. In particular, adults experiencing chronic psychological distress were significantly more likely than those exhibiting distress resistance to have experienced multiple and varied childhood maltreatment, adjusted odds ratio (AOR) = 3.30, 95% CI [0.37, 6.05], p = .002. Furthermore, adult experiences of assault were found to be associated with psychological distress. These findings have important implications for mental health, as well as interventions aimed at breaking the cycle of urban poverty. Specific focus on interpersonal trauma vulnerabilities is important. Prioritizing socioecological stability, with mental health needs assessed on an individual level, may be most appropriate. This work also highlights the need to direct future attention to barriers to access and facilitation of social support services.     

Reducing the Human Burden of Breast Cancer: Advanced Radiation Therapy Yields Improved Treatment Outcomes

Radiation therapy is an important modality in the treatment of patients with breast cancer. While its efficacy in the treatment of breast cancer was known shortly after the discovery of x‐rays, significant advances in radiation delivery over the past 20 years have resulted in improved patient outcomes. With the development of improved systemic therapy, optimizing local control has become increasingly important and has been shown to improve survival. Better understanding of the magnitude of treatment benefit, as well as patient and biological factors that confer an increased recurrence risk, have allowed radiation oncologists to better tailor treatment decisions to individual patients. Furthermore, significant technological advances have occurred that have reduced the acute and long‐term toxicity of radiation treatment. These advances continue to reduce the human burden of breast cancer. It is important for radiation oncologists and nonradiation oncologists to understand these advances, so that patients are appropriately educated about the risks and benefits of this important treatment modality.