Belzutifan: a novel therapeutic for the management of von Hippel-Lindau disease and beyond.

The identification of the VHL gene and its role in regulating the hypoxia-inducible factor signaling pathway has helped to revolutionize the treatment of renal cell carcinoma (RCC). Belzutifan is a novel small-molecule inhibitor of hypoxia-inducible factor 2α which has demonstrated efficacy in treating von Hippel-Lindau (VHL) disease, earning regulatory approvals for this indication. There is also early evidence for efficacy in sporadic RCC. Belzutifan has a favorable safety profile. Several clinical trials are currently ongoing, which should help in identifying this promising drug's role in RCC and beyond. This review summarizes the history, pharmacology and clinical evidence for belzutifan use to date, and also explores unanswered questions as they relate to this novel therapeutic agent.

The novel drug belzutifan was developed after years of research in identifying the VHL gene and how genetic abnormalities in VHL may result in tumor growth. Belzutifan has been approved for use in patients with VHL disease ­ a rare familial disorder first described in the 19th century that presents with a variety of cancerous and noncancerous tumors, including kidney cancer. Growing evidence supports belzutifan's use in non-familial kidney cancer as well. This is important because most patients eventually develop resistance to the currently available cancer treatments, highlighting the need for drugs with a different mechanism of action. Belzutifan works by blocking a protein called HIF-2a, which causes tumor growth in patients with VHL disease. Belzutifan is well tolerated, with the most common side effects being low energy, hemoglobin and blood oxygen. This review summarizes the history, mechanism of action and research evidence to date supporting the use of belzutifan in VHL disease and cancer treatment. We also discuss future directions, including remaining clinical questions and areas of ongoing research.

Performance status, comorbidities, and cycles of methotrexate exert the greatest influence on outcomes of primary and secondary CNS lymphomas: the Lexington experience.

Primary central nervous system lymphoma (PCNSL) occurs primarily in older patients and has a worse prognosis than other extranodal lymphomas. Contemporary treatment is based on high-dose methotrexate (HD-MTX), which crosses the blood-brain barrier. Secondary CNS lymphoma (SCNSL) can occur concomitantly with systemic lymphoma or later at relapse and generally has a dismal outcome. We reviewed disease characteristics and outcomes of 103 patients (44 PCNSL and 59 SCNSL) treated at our center between 2015 and 2020. Median ages at diagnosis were 64 and 62 years, respectively. In both groups, diffuse large B cell lymphoma (DLBCL) was the major histologic type; in SCNSL, other types were also seen. SCNSL, in contrast with PCNSL, manifested with smaller tumors or cerebrospinal fluid positivity. For SCNSL the mean interval to brain involvement was 18 months (0-138). The overall survival had a trend to worse in SCNSL; median survival 11 months versus 61 months in PCNSL (p = 0.089). Progression-free survival was similar in both groups. A significant proportion of SCNSL patients with poor performance status could not obtain CNS-directed treatments. The strongest predictor of poor outcome was ECOG performance status 2 + at diagnosis for both groups. Charlson comorbidity index was predictive only for the PCNSL cohort. Tumor size was not prognostic for survival. The number of HD-MTX cycles correlated with survival, whereas the regimen itself and average cumulative dose of methotrexate did not play a role. Our study is in line with the recent literature and confirms ongoing challenges. We discuss how the outcomes of CNS lymphomas can be improved.

Key Considerations for the Treatment of Advanced Breast Cancer in Older Adults: An Expert Consensus of the Canadian Treatment Landscape.

The prevalence of breast cancer amongst older adults in Canada is increasing. This patient population faces unique challenges in the management of breast cancer, as older adults often have distinct biological, psychosocial, and treatment-related considerations. This paper presents an expert consensus of the Canadian treatment landscape, focusing on key considerations for optimizing selection of systemic therapy for advanced breast cancer in older adults. This paper aims to provide evidence-based recommendations and practical guidance for healthcare professionals involved in the care of older adults with breast cancer. By recognizing and addressing the specific needs of older adults, healthcare providers can optimize treatment outcomes and improve the overall quality of care for this population.

Spontaneous regression of metastatic hepatocellular carcinoma following 3 weeks of lenvatinib.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality and is associated with a poor prognosis. Rarely, there is spontaneous regression of the tumour. We present a case of a middle-aged male with presumed metastatic HCC who experienced enduring regression following 3 weeks of lenvatinib, which was discontinued due to side effects. While this could represent an unusually successful response to therapy, spontaneous tumour regression or an alternative diagnosis should be considered. We discuss possible mechanisms that might explain this unusual case and advocate for tissue confirmation in select cases, where there is diagnostic doubt or when the disease pattern does not clearly follow the recognised natural history. Therefore, if regression occurs-whether spontaneous or in response to treatment-it can be better understood and subsequent therapies recommended.

Observational Study of Qigong as a Complementary Self-Care Practice at a Tertiary-Care Pain Management Unit.

Qigong, which can be characterized in many different ways, is offered as a complementary self-care practice at a tertiary-care pain management unit in Halifax, Nova Scotia. This report provides a quantitative and qualitative assessment of two groups engaged in qigong practice in this context as part of two Research in Medicine (RIM) projects (2014-15, 2016-17). It includes assessments of pain, mood, quality of life, sleep, and fatigue, considers outcomes in relation to the amount of practice, and considers whether health attitudes would help determine who might benefit from the practice. There were 43 participants (28 ongoing practitioners, 15 new to qigong). The ongoing practice group in RIM2 had significant benefits over time in pain, mood, quality of life, and fatigue in quantitative scores, but changes were not significant in RIM 1. There were no differences in any measures in those new to qigong. Qualitative comments in core and other domains reflected good or better outcomes in 16 subjects in the ongoing group who practiced consistently. In those who practiced less, results were more variable. In most of those new to qigong, the practice was limited and comments indicate minimal changes. Those engaged in qigong have a stronger internal health locus of control than control subjects. Diligent qigong practice provides multiple health benefits for those with chronic pain, and qualitative assessments are essential for documenting these effects. For those new to qigong, factors needed to effectively engage practice need to be explored further to optimize program delivery. The trial is registered with http://www.clinicaltrials.gov (NCT04279639).

Efficacy of a conversion from filgrastim to filgrastim-sndz in stem cell transplant patients undergoing mobilization.

During autologous stem cell transplant, granulocyte colony-stimulating factors (G-CSF) serve the integral role of mobilizing hematopoietic cells into the peripheral blood for subsequent collection by leukapheresis. Filgrastim (Neupogen®) is a G-CSF and affects hematopoietic cells by stimulating growth and differentiation of neutrophils. Filgrastim-sndz (Zarxio®), a biosimilar of filgrastim, received landmark approval as the first biosimilar product approved by the FDA in the United States. As a result of the recent FDA approval, our medical center made the conversion in August 2016 from using filgrastim to filgrastim-sndz to provide patients the same benefits of the filgrastim injection at a reduced cost. This retrospective, observational cohort study evaluated the comparative efficacy of the filgrastim-sndz biosimilar in 147 patients who underwent mobilization prior to stem cell transplant with filgrastim between 1 August 2015 and 31 July 2016 or filgrastim-sndz between 1 September 2016 and 30 November 2017. The mean number of CD34 cells collected during apheresis was 7.38 × 106 in the filgrastim group and 8.86 × 106 in the filgrastim-sndz group. Filgrastim-sndz was significantly non-inferior, as the difference between filgrastim and filgrastim-sndz was -1.48 × 106 with an upper 95% confidence bound equal to -0.24 × 106 that did not include the non-inferiority margin of 1 × 106 (p = 0.0006). The median number of days of apheresis was 2 in both groups (p= 0.3273). In conclusion, the biosimilar product was non-inferior for mobilization and the conversion from filgrastim to filgrastim-sndz afforded patients similar efficacy for mobilization in stem cell transplant at a reduced cost.

Understanding families' experiences following a diagnosis of non-syndromic craniosynostosis: a qualitative study.

OBJECTIVES: Craniosynostosis is typically diagnosed and surgically corrected within the first year of life. The diagnosis and surgical correction of the condition can be a very stressful experience for families. Despite this, there is little research exploring the impact that craniosynostosis has on families, especially in the period immediately following diagnosis and correction. In this study, the authors aimed to qualitatively examine the psychosocial experience of families with a child diagnosed with craniosynostosis. DESIGN: Qualitative study. SETTING: Tertiary care paediatric health centre. PARTICIPANTS: Mothers of children newly diagnosed with single-suture, non-syndromic craniosynostosis. INTERVENTION: Semistructured interviews regarding parental experience with the initial diagnosis, their decision on corrective surgery for their child, the operative experience, the impact of craniosynostosis on the family and the challenges they encountered throughout their journey. PRIMARY AND SECONDARY OUTCOME MEASURES: Thematic analysis, a type of qualitative analysis that provides an in-depth account of participant's experiences, was used to analyse the interview data. RESULTS: Over a 4-year period, 12 families meeting eligibility criteria completed the study. Three main themes (six subthemes) emerged from the preoperative interviews: frustration with diagnostic delays (parental intuition and advocacy, hope for improved awareness), understanding what to expect (healthcare supports, interest in connecting with other families) and justifying the need for corrective surgery (influence of the surgeon, struggle with cosmetic indications). Two main themes (four subthemes) were drawn from the postoperative interviews: overcoming fear (the role of healthcare professionals, transition home) and relief (reduction in parental anxiety, cosmetic improvements). CONCLUSIONS: Overall, the diagnosis of craniosynostosis has a profound impact on families, leading them to face many struggles throughout their journey. A better understanding of these experiences will help to inform future practice, with a hope to improve this experience for other families moving forward.

Atrichia with papular lesions: A case report.

We present a case of clinically suspected atrichia with papular lesions in an 8-year-old male presenting with alopecia universalis and keratotic papules. We review the literature available on this rare genodermatosis.