High dose rate brachytherapy in the management of anal cancer: A review.

PURPOSE: To conduct a systematic review evaluating the impact of high dose rate (HDR) brachytherapy (BT) on the clinical outcomes and toxicities of patients with anal cancer. METHODS AND MATERIALS: A search of Medline, Embase, and Cochrane Library databases was performed using search terms: "anal", "anal canal", "squamous", "adenocarcinoma", "cancer", "neoplasm", in combination with "brachytherapy", "high dose rate brachytherapy" or "HDR brachytherapy". Additional studies were identified after scanning references. Studies published in English with ≥10 patients were included. RESULTS: Ten studies (n = 448) were included in this review. 321 patients were treated with curative intent external beam radiotherapy (EBRT), chemotherapy (CT) and HDRBT; of those, 312 and 9 received interstitial and intraluminal BT, respectively. Mean follow up was 39.9 months (range (R): 24-61 months). Complete response was noted between 80%-93% and local control ranged between 81%-88%. Mean rate of local failure was 12.3% (SD 3.6%, R: 8%-18%). Distant failure rate was reported between 2%-3% and metastasis free survival ranged between 82%-88%. Mean disease free survival and overall survival were 77.3% (SD 6.6%, R: 66%-100%) and 82.5% (SD 13.7%, R: 70%-87.7%). Acute toxicity was mostly grade 1/2 dermatitis, proctitis or cystitis; G3 or higher toxicity was reported only in 4 patients in 2 studies (dermatitis n = 3 and sphincter necrosis n = 1). Most common long term toxicities were incontinence (2.5%-9%) and proctitis (2.5%-19%); G3/4 toxicity ranged between 2.2%-7.1%. Mean sphincter preservation rate and colostomy free survival was 88.0% and 80.4%, respectively. CONCLUSION: Pooled analysis in this review suggests excellent response, local control and survival with HDRBT in combination with EBRT and CT, with limited toxicity. Prospective well conducted trials are needed to further establish role of HDRBT management of anal cancer with future focus on development of international consensus on patient selection, dosimetric parameters, treatment sequencing as well as defining uniform outcome and toxicity assessment.

Cancer treatment-related financial toxicity experienced by patients in low- and middle-income countries: a scoping review.

PURPOSE: In the past decade, literature has called attention to financial toxicities experienced by cancer patients. Though studies have addressed research questions in high-income countries, there remains a paucity of in-depth reviews regarding low- and middle-income countries (LMICs). Our scoping review provides an overview of treatment-related financial toxicities experienced by cancer patients in LMICs. METHODS: A systematic search was conducted in MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials. English peer-reviewed articles that (a) explored patients' experience with financial toxicity due to cancer treatment (b) were specific to LMICs as defined by the World Bank and (c) focused on qualitative data were included. Details regarding participants and main findings were extracted and synthesized. RESULTS: The search yielded 6290 citations, and 42 studies across 3 low-income, 9 lower-middle-income and 8 upper-middle-income countries. Main themes identified included cancer patients encountered various material hardships, managed costs with different coping behaviours and experienced negative psychological responses to their financial burden. Higher levels of financial toxicities were associated with patient characteristics such as lower socio-economic status and lack of insurance, as well as patient outcomes such as lower quality of life. CONCLUSION: Cancer patients in LMIC experience deleterious financial toxicities as a result of treatment. This comprehensive characterization of financial toxicities will better allow health systems to adopt evidence-based mitigation strategies to reduce the financial burden on patients.

Chronic early-life social isolation affects NMDA and TrkB receptor expression in a sex-specific manner.

Exposing mammals to adverse social environments early in life can affect brain development in ways that alter adult behaviour. For example, chronic, early-life social isolation (CELSI) has been found to cause novelty-induced hyperactivity, impaired pre-pulse inhibition, and enhanced anxiety-related behaviour. Although the molecular mechanism(s) underlying the embedding of CELSI have not been fully elucidated, evidence suggests changes in the level of excitatory neurotransmission and neurotrophic factor signalling may be quite important. Since much of the work in this area has focused upon mRNA-level analyses, and has shown variable responses across both brain region and animal sex, our study aimed to explore the impact of CELSI on the expression of two important plasticity-related proteins (Tropomyosin receptor kinase B and the GluN2B subunit of the NMDA receptor) in the pre-frontal cortex and hippocampus of both male and female rats. We observed that the expression of both proteins was clearly changed by CELSI, but that the effect occurred in a sex (but not region) specific manner. Our results support the growing view that early-life adversity can cause structural changes reasonably associated with adult behaviour, and emphasise that the study of such changes benefits from a sex-based analysis.