A multicentre study of the evidence for customized margins in photon breast boost radiotherapy.

Objective To determine if subsets of patients may benefit from smaller or larger margins when using laser setup and bony anatomy verification of breast tumour bed (TB) boost radiotherapy (RT).Methods Verification imaging data acquired using cone-beam CT, megavoltage CT or two-dimensional kilovoltage imaging on 218 patients were used (1574 images). TB setup errors for laser-only setup (dlaser) and for bony anatomy verification (dbone) were determined using clips implanted into the TB as a gold standard for the TB position. Cases were grouped by centre-, patient- and treatment-related factors, including breast volume, TB position, seroma visibility and surgical technique. Systematic (Σ) and random (σ) TB setup errors were compared between groups, and TB planning target volume margins (MTB) were calculated.Results For the study population, Σlaser was between 2.8 and 3.4 mm, and Σbone was between 2.2 and 2.6 mm, respectively. Females with larger breasts (p = 0.03), easily visible seroma (p ≤ 0.02) and open surgical technique (p ≤ 0.04) had larger Σlaser. Σbone was larger for females with larger breasts (p = 0.02) and lateral tumours (p = 0.04). Females with medial tumours (p < 0.01) had smaller Σbone.Conclusion If clips are not used, margins should be 8 and 10 mm for bony anatomy verification and laser setup, respectively. Individualization of TB margins may be considered based on breast volume, TB and seroma visibility.Advances in knowledge Setup accuracy using lasers and bony anatomy is influenced by patient and treatment factors. Some patients may benefit from clip-based image guidance more than others

Apolipoprotein C3 Polymorphisms, Cognitive Function and Diabetes in Caribbean Origin Hispanics

Apolipoprotein C3 (APOC3) modulates triglyceride metabolism through inhibition of lipoprotein lipase, but is itself regulated by insulin, so that APOC3 represents a potential mechanism by which glucose metabolism may affect lipid metabolism. Unfavorable lipoprotein profiles and impaired glucose metabolism are linked to cognitive decline, and all three conditions may decrease lifespan. Associations between apolipoprotein C3 (APOC3) gene polymorphisms and impaired lipid and glucose metabolism are well-established, but potential connections between APOC3 polymorphisms, cognitive decline and diabetes deserve further attention.We examined whether APOC3 single nucleotide polymorphisms (SNPs) m482 (rs2854117) and 3u386 (rs5128) were related to cognitive measures, whether the associations between cognitive differences and genotype were related to metabolic differences, and how diabetes status affected these associations. Study subjects were Hispanics of Caribbean origin (n = 991, aged 45-74) living in the Boston metropolitan area.Cognitive and metabolic measures differed substantially by type II diabetes status. In multivariate regression models, APOC3 m482 AA subjects with diabetes exhibited lower executive function (P = 0.009), Stroop color naming score (P = 0.014) and Stroop color-word score (P = 0.022) compared to AG/GG subjects. APOC3 m482 AA subjects with diabetes exhibited significantly higher glucose (P = 0.032) and total cholesterol (P = 0.028) compared to AG/GG subjects. APOC3 3u386 GC/GG subjects with diabetes exhibited significantly higher triglyceride (P = 0.004), total cholesterol (P = 0.003) and glucose (P = 0.016) compared to CC subjects.In summary, we identified significant associations between APOC3 polymorphisms, impaired cognition and metabolic dysregulation in Caribbean Hispanics with diabetes. Further research investigating these relationships in other populations is warranted

Normal tissue complication probability (NTCP) parameters for breast fibrosis: Pooled results from two randomised trials

Introduction The dose-volume effect of radiation therapy on breast tissue is poorly understood. We estimate NTCP parameters for breast fibrosis after external beam radiotherapy. Materials and methods We pooled individual patient data of 5856 patients from 2 trials including whole breast irradiation followed with or without a boost. A two-compartment dose volume histogram model was used with boost volume as the first compartment and the remaining breast volume as second compartment. Results from START-pilot trial (n = 1410) were used to test the predicted models. Results 26.8% patients in the Cambridge trial (5 years) and 20.7% patients in the EORTC trial (10 years) developed moderate-severe breast fibrosis. The best fit NTCP parameters were BEUD(50) = 136.4 Gy, γ50 = 0.9 and n = 0.011 for the Niemierko model and BEUD (50) = 132 Gy, m = 0.35 and n = 0.012 for the Lyman Kutcher Burman model. The observed rates of fibrosis in the START-pilot trial agreed well with the predicted rates. Conclusions This large multi-centre pooled study suggests that the effect of volume parameter is small and the maximum RT dose is the most important parameter to influence breast fibrosis. A small value of volume parameter 'n' does not fit with the hypothesis that breast tissue is a parallel organ. However, this may reflect limitations in our current scoring system of fibrosis. © 2013 Elsevier Ireland Ltd. All rights reserved

A multicentre study of the evidence for customized margins in photon breast boost radiotherapy.

OBJECTIVE: To determine if subsets of patients may benefit from smaller or larger margins when using laser setup and bony anatomy verification of breast tumour bed (TB) boost radiotherapy (RT). METHODS: Verification imaging data acquired using cone-beam CT, megavoltage CT or two-dimensional kilovoltage imaging on 218 patients were used (1574 images). TB setup errors for laser-only setup (dlaser) and for bony anatomy verification (dbone) were determined using clips implanted into the TB as a gold standard for the TB position. Cases were grouped by centre-, patient- and treatment-related factors, including breast volume, TB position, seroma visibility and surgical technique. Systematic (Σ) and random (σ) TB setup errors were compared between groups, and TB planning target volume margins (MTB) were calculated. RESULTS: For the study population, Σlaser was between 2.8 and 3.4 mm, and Σbone was between 2.2 and 2.6 mm, respectively. Females with larger breasts (p = 0.03), easily visible seroma (p ≤ 0.02) and open surgical technique (p ≤ 0.04) had larger Σlaser. Σbone was larger for females with larger breasts (p = 0.02) and lateral tumours (p = 0.04). Females with medial tumours (p < 0.01) had smaller Σbone. CONCLUSION: If clips are not used, margins should be 8 and 10 mm for bony anatomy verification and laser setup, respectively. Individualization of TB margins may be considered based on breast volume, TB and seroma visibility. Advances in knowledge: Setup accuracy using lasers and bony anatomy is influenced by patient and treatment factors. Some patients may benefit from clip-based image guidance more than others