Individual benefit in heart sparing during DIBH-supported left breast radiotherapy.

Introduction: Deep-inspirational breath hold (DIBH) is an option for heart protection in breast radiotherapy; we intended to study its individual benefit. Materials and Methods: 3DCRT treatment planning was performed in a cohort of 103 patients receiving radiotherapy of the whole breast (WBI)/chest wall (CWI) ± nodal regions (NI) both under DIBH and free breathing (FB) in the supine position, and in the WBI only cases prone (n = 45) position, too. A series of patient-related and heart dosimetry parameters were analyzed. Results: The DIBH technique provided dramatic reduction of all heart dosimetry parameters the individual benefit, however, varied. In the whole population the best predictor of benefit was the ratio of ipsilateral lung volume (ILV)FB and ILVDIBH. In the WBI cohort 9-11 patients and 5-8 patients received less dose to selected heart structures with the DIBH and prone positioning, respectively; based on meeting various dose constraints DIBH was the only solution in 6-13 cases, and prone positioning in 5-6 cases. In addition to other excellent predictors, a small ILVFB or ILVDIBH with outstanding predicting performance (AUC ≥ 0.90) suggested prone positioning. Detailed analysis consistently indicated the outstanding performance of ILVFB and ILVDIBH in predicting the benefit of one over the other technique in lowering the mean heart dose (MHD), left anterior descending coronary artery (LAD) mean dose and left ventricle(LV)-V5Gy. The preference of prone positioning was further confirmed by anatomical parameters measured on a single CT scan at the middle of the heart. Performing spirometry in a cohort of 12 patients, vital capacity showed the strongest correlation with ILVFB and ILVDIBH hence this test could be evaluated as a clinical tool for patient selection. Discussion: Individual lung volume measures estimated by spirometry and anatomical data examined prior to acquiring planning CT may support the preference of DIBH or prone radiotherapy for optimal heart protection.

Deep-inspirational breath-hold (DIBH) technique in left-sided breast cancer: various aspects of clinical utility.

BACKGROUND: Studying the clinical utility of deep-inspirational breath-hold (DIBH) in left breast cancer radiotherapy (RT) was aimed at focusing on dosimetry and feasibility aspects. METHODS: In this prospective trial all enrolled patients went through planning CT in supine position under both DIBH and free breathing (FB); in whole breast irradiation (WBI) cases prone CT was also taken. In 3-dimensional conformal radiotherapy (3DCRT) plans heart, left anterior descending coronary artery (LAD), ipsilateral lung and contralateral breast doses were analyzed. The acceptance of DIBH technique as reported by the patients and the staff was analyzed; post-RT side-effects including radiation lung changes (visual scores and lung density measurements) were collected. RESULTS: Among 130 enrolled patients 26 were not suitable for the technique while in 16, heart or LAD dose constraints were not met in the DIBH plans. Among 54 and 34 patients receiving WBI and postmastectomy/nodal RT, respectively with DIBH, mean heart dose (MHD) was reduced to < 50%, the heart V25 Gy to < 20%, the LAD mean dose to < 40% and the LAD maximum dose to about 50% as compared to that under FB; the magnitude of benefit was related to the relative increase of the ipsilateral lung volume at DIBH. Nevertheless, heart and LAD dose differences (DIBH vs. FB) individually varied. Among the WBI cases at least one heart/LAD dose parameter was more favorable in the prone or in the supine FB plan in 15 and 4 cases, respectively; differences were numerically small. All DIBH patients completed the RT, inter-fraction repositioning accuracy and radiation side-effects were similar to that of other breast RT techniques. Both the patients and radiographers were satisfied with the technique. CONCLUSIONS: DIBH is an excellent heart sparing technique in breast RT, but about one-third of the patients do not benefit from that otherwise laborious procedure or benefit less than from an alternative method. TRIAL REGISTRATION: retrospectively registered under ISRCTN14360721 (February 12, 2021).

Breakfast Consumption in the UK: Patterns, Nutrient Intake and Diet Quality. A Study from the International Breakfast Research Initiative Group.

Breakfast consumption is associated with higher overall dietary adequacy; however, there is a lack of quantitative guidelines for optimal nutrient intakes at breakfast in the UK. This study aimed to investigate nutrient and food group intakes at breakfast and examine their relationship to overall Diet Quality (DQ). Data from the most recent National Diet and Nutrition Survey (NDNS, 2008⁻2014) were accessed to provide a representative sample (n = 8174) of the UK population, aged 5⁻96 years, mean age of 33 years. Food intake was measured by a 4-day estimated food diary and DQ was assessed by the Nutrient Rich Food Index 9.3 method. Energy- and socio-economic-adjusted nutrient and food group intakes were compared across age groups and DQ tertiles by ANCOVA. Breakfast contributed 20⁻22% to total energy intake. Breakfast intakes of carbohydrate and non-milk extrinsic sugars (NMES) were higher, and intakes of protein, total fat and saturated fatty acid (SFA) were lower, than relative daily intakes. Breakfast was particularly rich in B vitamins, vitamin D, calcium, iron, iodine and magnesium. From the lowest to the highest DQ tertile decreasing intakes of NMES, SFA and total fat and increasing intakes of carbohydrate, protein, fibre and most micronutrients were found. These findings could help to inform the development of nutrient-based recommendations for a balanced breakfast for the first time in the UK.

A simple clinical method for predicting the benefit of prone vs. supine positioning in reducing heart exposure during left breast radiotherapy.

BACKGROUND AND PURPOSE: The benefit of reduced radiation heart exposure in the prone vs. supine position individually differs. In this prospective cohort study, the goal was to develop a simple method for the operation of a validated model for the prediction of preferable treatment position during left breast radiotherapy. MATERIAL AND METHODS: In 100 cases, a single CT slice was utilized for the collection of the needed patient-specific data (in addition to body mass index, the distance of the LAD from the chest wall and the area of the heart included in the radiation fields at the middle of the heart in the supine position). Outcome was analyzed in relation to the full CT series acquired in both positions and dosimetric data. RESULTS: Great consistency was found between the tested and original method regarding sensitivity and specificity. The prioritization of LAD dose, and the use of heart dose and position-specific dose constraints as safety measures ensure sensitivity and specificity values of 82.8% and 87.3%, respectively. In an additional "routine clinical practice" series of 60 patients the new method seemed feasible in routine clinical practice. External testing on a 28-case series indicated similar accuracy. CONCLUSION: We consider this simple clinical tool appropriate for assisting individual positioning aiming at maximum heart protection during left breast irradiation.

Interaction between TCF7L2 polymorphism and dietary fat intake on high density lipoprotein cholesterol.

Recent evidence suggests that lifestyle factors influence the association between the Melanocortin 4 receptor (MC4R) and Transcription Factor 7-Like 2 (TCF7L2) gene variants and cardio-metabolic traits in several populations; however, the available research is limited among the Asian Indian population. Hence, the present study examined whether the association between the MC4R single nucleotide polymorphism (SNP) (rs17782313) and two SNPs of the TCF7L2 gene (rs12255372 and rs7903146) and cardio-metabolic traits is modified by dietary factors and physical activity. This cross sectional study included a random sample of normal glucose tolerant (NGT) (n = 821) and participants with type 2 diabetes (T2D) (n = 861) recruited from the urban part of the Chennai Urban Rural Epidemiology Study (CURES). A validated food frequency questionnaire (FFQ) was used for dietary assessment and self-reported physical activity measures were collected. The threshold for significance was set at P = 0.00023 based on Bonferroni correction for multiple testing [(0.05/210 (3 SNPs x 14 outcomes x 5 lifestyle factors)]. After Bonferroni correction, there was a significant interaction between the TCF7L2 rs12255372 SNP and fat intake (g/day) (Pinteraction = 0.0001) on high-density lipoprotein cholesterol (HDL-C), where the 'T' allele carriers in the lowest tertile of total fat intake had higher HDL-C (P = 0.008) and those in the highest tertile (P = 0.017) had lower HDL-C compared to the GG homozygotes. In a secondary analysis of SNPs with the subtypes of fat, there was also a significant interaction between the SNP rs12255372 and polyunsaturated fatty acids (PUFA, g/day) (Pinteraction<0.0001) on HDL-C, where the minor allele carriers had higher HDL-C in the lowest PUFA tertile (P = 0.024) and those in the highest PUFA tertile had lower HDL-C (P = 0.028) than GG homozygotes. In addition, a significant interaction was also seen between TCF7L2 SNP rs12255372 and fibre intake (g/day) on HDL-C (Pinteraction<0.0001). None of the other interactions between the SNPs and lifestyle factors were statistically significant after correction for multiple testing. Our findings indicate that the association between TCF7L2 SNP rs12255372 and HDL-C may be modified by dietary fat intake in this Asian Indian population.

[Role of 18FDG-PET/CT in the management and gross tumor volume definition for radiotherapy of head and neck cancer; single institution experiences based on long-term follow-up]. / 18FDG-PET/CT szerepe fej-nyak daganatok kezelésében és a sugárterápiás tumortérfogat meghatározásában - Az SZTE Onkoterápiás Klinika eredményeinek értékelése.

The purpose of our work is evaluation of the impact of 18FDG-PET/CT on the complex management of locoregionally advanced (T3-4N1-3) head and neck squamous cell cancer (LAHNSC), and on the target definition for 3D conformal (3DCRT) and intensity-modulated radiotherapy (IMRT). 18FDG-PET/CT were performed on 185 patients with LAHNSC prior to radiotherapy/chemoradiation in the treatment position between 2006 and 2011. Prior to it 91 patients received induction chemotherapy (in 20 cases of these, baseline PET/CT was also available). The independently delineated CT-based gross tumor volume (GTVct) and PET/CT based ones (GTVpet) were compared. Impact of PET/CT on the treatment strategy, on tumor response evaluation to ICT, on GTV definition furthermore on overall and disease-specific survival (OS, DSS) was analysed. PET/CT revealed 10 head and neck, 2 lung cancers for 15 patients with carcinoma of unknown primary (CUP) while 3 remained unknown. Second tumors were detected in 8 (4.4%), distant metastasis in 15 (8.2%) cases. The difference between GTVct and GTVpet was significant (p=0.001). In 16 patients (14%) the GTVpet were larger than GTVct due to multifocal manifestations in the laryngo-pharyngeal regions (4 cases) or lymph node metastases (12 cases). In the majority of the cases (82 pts, 72%) PET/CT-based conturing resulted in remarkable decrease in the volume (15-20%: 4 cases, 20-50%: 46 cases, >50%: 32 cases). On the basis of the initial and post-ICT PET/CT comparison in 15/20 patients more than 50% volume reduction and in 6/20 cases complete response were achieved. After an average of 6.4 years of follow-up the OS (median: 18.3±2.6 months) and DSS (median: 25.0±4.0 months) exhibited close correlation (p=0.0001) to the GTVpet. In cases with GTVpet <10 cm3 prior to RT, DSS did not reach the median, the mean is 82.1±6.1 months, while in cases with GTVpet 10-40 cm3 the median of the DSS was 28.8±4.9 months (HR = 3.57; 95% CI: 1.5-8.3), and in those with GTVpet >40 cm3 the median DSS was 8.4±0.96 months (HR= 11.48; 95% CI: 5.3-24.9). Our results suggest that 18FDG-PET/CT plays an important role for patient with LAHNSC, by modifying the treatment concept and improving the target definition for selective RT modalities. Volumetric PET/CT-based assessment of the tumor response after ICT gives valuable contribution to further therapy planning.

Casting-type calcifications on the mammogram suggest a higher probability of early relapse and death among high-risk breast cancer patients.

INTRODUCTION: A retrospective analysis of the relation between the presence of casting-type calcifications on the mammogram and the prognosis of breast cancer was performed. MATERIALS AND METHODS: The mammographic tumor features and other characteristics (invasive tumor size, histological tumor type, grade, nodal, hormone receptor and HER2 status, presence of lymphovascular invasion) of 55 high-risk breast cancers were studied. RESULTS: After a median follow-up time of 29.1 months, the median relapse-free survival and overall survival times among breast cancer patients with tumors associated with casting calcifications were 26.6 and 29.6 months, respectively. The corresponding parameters among patients with tumors not accompanied by casting calcifications were 54.4 and > 58.5 months, respectively. Significant associations were found between the presence of casting calcifications and the risks of relapse (HR = 3.048, 95% CI: 1.116-8.323, p = 0.030) or death (HR = 3.504, 95% CI: 1.074-11.427, p = 0.038). Positive associations were found between casting calcifications and ER/PR negativity (p = 0.015 and p = 0.003, respectively) and HER2 overexpression (p = 0.019). DISCUSSION: Our findings support the theory that breast tumors associated with casting-type calcifications at mammography comprise a disease entity which exhibits significantly more aggressive behavior and a poorer outcome than do cancers with other mammographic tumor features.

Investigation of penetratin peptides. Part 2. In vitro uptake of penetratin and two of its derivatives.

As endocytic uptake of the Antennapedia homeodomain-derived penetratin peptide (RQIKIWFQNRRMKWKK) is finally being revealed, some of the early views about penetratin need to be reconsidered. Endocytic uptake seems to contradict the indispensability of tryptophans and also the minimum length of 16 amino acid residues for efficient internalization. To revise the membrane translocation of penetratin, two penetratin analogs were designed and synthesized: a peptide in which tryptophans were replaced by phenylalanines (Phe(6,14)-penetratin, RQIKIFFQNRRMKFKK) and a shortened analog (dodeca-penetratin, RQIKIWF-R-KWKK) made up of only 12 residues. The peptides were fluorescently labeled and applied to live, unfixed cells from various lines. Cellular uptake was analysed by confocal microscopy and flow cytometry. Low temperature or ATP-depletion blocked the intracellular entry of all three penetratin peptides. A decrease in membrane fluidity or cholesterol depletion with methyl-beta-cyclodextrin greatly inhibited peptide uptake, showing the involvement of cholesterol-rich lipid rafts in internalization. Exogenous heparan sulfate also diminished the internalization of penetratin and its derivatives, reflecting the paramount importance of electrostatic interactions with polyanionic cell-surface proteoglycans. The beneficial presence of tryptophans is supported by observations on the decreased cellular uptake of Phe(6, 14)-penetratin. The maintained translocational efficiency of dodeca-penetratin demonstrates that a thorough understanding of penetratin internalization can yield new penetratin analogs with unaltered translocational abilities. This study provides evidence on the energy-dependent and lipid raft-mediated endocytic uptake of penetratin and highlights the necessity of revealing those pathways that cationic cell-penetrating peptides employ to enter live cells.