Safety and tolerability of radiotherapy in combination with systemic targeted therapies for treatment of hepatocellular carcinoma: a narrative review.

BACKGROUND AND OBJECTIVE: Palliative radiotherapy (RT) and systemic immuno- or targeted therapy both play significant roles in the treatment of advanced hepatocellular carcinoma (HCC). Concurrent application of these therapies is increasing, however, no guidelines exist regarding the combination of systemic therapy with RT. This narrative review summarises the existing literature reporting toxicity observed after concurrent treatment with RT and immuno- or targeted therapeutic agents commonly used in HCC. METHODS: The PubMed database was searched for studies published between 2011 and 2023 reporting toxicity data on patients treated concurrently with RT and targeted agents used in HCC. Due to the paucity of relevant literature in HCC, the inclusion criteria were expanded to include non-HCC cohorts treated with targeted therapies commonly used in advanced HCC. KEY CONTENT AND FINDINGS: Sixty-seven articles were included in this review. Twenty-two articles reported combined RT with sorafenib, one with regorafenib, 22 with bevacizumab, three with lenvatinib and 19 with immune checkpoint inhibitors. Significant findings include a high rate severe hepatotoxicity with combination RT and sorafenib, ranging from 0-19% with liver stereotactic body radiotherapy (SBRT) and 3-18% with conventionally fractionated liver RT. Severe gastrointestinal (GI) toxicities including perforation and ulceration were seen with combination bevacizumab and RT, ranging from 0-27% in the acute setting and 0-23% in the late setting. The safety profile of combination immune checkpoint blockade agents and RT was similar to that seen in monotherapy. CONCLUSIONS: Existing data suggests that combination RT and targeted therapy given the risk of severe adverse events including hepatotoxicity and GI toxicity. There is an urgent need for future studies specifically examining the impact of combination therapy in HCC patients to guide clinical decision-making in the evolving landscape of immune- and targeted therapies.

Efficacy and Safety of Anti-angiogenic Agents for Cancer Patients With Proteinuria or a History of Proteinuria: A Systematic Review.

BACKGROUND/AIM: The safety and efficacy of anti-angiogenic agents in patients with cancer with proteinuria and a history of proteinuria are not well established. This systematic review aimed to answer these questions. MATERIALS AND METHODS: We searched three electronic databases for articles published until June 18, 2021. The main outcomes used were "death", "renal impairment", and "proteinuria impairment". RESULTS: After screening 303 references in the PubMed, Cochrane Library, and ICHUSHI-web databases, this review included five studies on renal cell carcinoma (RCC). In patients with metastatic RCC, the hazard ratio of the presence of (or having) proteinuria (1+ or higher) at baseline was 0.82 (0.23-2.97); thus, proteinuria was not significantly associated with the outcome of death. No significant deterioration in kidney function was observed in patients with proteinuria. Although proteinuria at baseline was a significant risk factor for proteinuria progression during and after treatment, most patients maintained grade 1 or 2 proteinuria and continued treatment without dose reduction or discontinuation. CONCLUSION: While weak evidence suggests that proteinuria at the start of treatment with anti-angiogenic agents might be a risk factor for worsening proteinuria, it was not significantly associated with death or renal impairment.

Estrategias en el tratamiento de la retinopatía diabética / Treatment strategies for diabetic retinopathy

Con este trabajo nos proponemos revisar las evidencias científicas relacionadas con el tratamiento de la retinopatía diabética. Para la investigación documental se examinaron los artículos de la temática indexados en las bases de datos Pubmed, Pubmed Central y Scielo, que correspondieron a los descriptores DeCs-MeSH: retinopatía diabética y tratamiento actual. La evaluación de los datos se realizó mediante el análisis de contenido de tipo directo. El progreso de la retinopatía diabética va desde los estados más benignos hasta los más severos cuando no se aplica una intervención médica apropiada. Es importante reconocer cada estado de la retinopatía diabética para que el tratamiento sea más efectivo. Varias décadas de estudios clínicos han proporcionado excelentes datos sobre el curso natural de la enfermedad y la estrategia de tratamiento que son efectivas en alrededor de un 90 por ciento para prevenir la pérdida visual severa(AU)

The purpose of the study was to present scientific evidence associated with the treatment of diabetic retinopathy. Document analysis was conducted based on examination of papers about the topic indexed in the databases PubMed, PubMed Central and SciELO, using the DeCs-MeSH terms 'diabetic retinopathy' and 'current treatment'. Data were evaluated with the method of direct content analysis. Diabetic retinopathy evolves from its most benign stages to the severest when appropriate medical action is not taken. It is important to identify each stage of diabetic retinopathy and apply the most effective treatment. Several decades of clinical studies have provided excellent data about the natural course of the disease, as well as about treatment strategies which are effective in around 90 percent of the cases to prevent severe visual loss(AU)