Progesterone and Luteinizing hormone secretion patterns in early pregnant gilts

Abstract We studied luteinizing hormone (LH) pulsatility and episodic progesterone release of the corpus luteum (CL) on Day 11 and Day 21 in inseminated gilts and aimed to establish a relationship between these two hormones. Blood was collected at 15-minute intervals for 12 hours on Days 11, 16, and 21 from a vena cava caudalis catheter. At euthanasia eight gilts were pregnant and six gilts were not pregnant. Progesterone parameters (basal, mean, pulse frequency, and pulse amplitude) did not differ between pregnant and non-pregnant gilts on Day 11, LH pulse frequency and amplitude tended to differ (p = 0.07 and p = 0.079). In pregnant gilts basal and mean progesterone, progesterone pulse amplitude and frequency declined significantly from Day 11 to Day 21 (p <0.05). A significant decline was also seen in the LH pulse amplitude from Day 11 to Day 21 (p <0.05). None of the LH pulses was followed by a progesterone pulse within 1 hour on Day 21. On Day 11 and Day 21 appeared a synchronicity in the LH pulse pattern, as there were two or three LH pulses in 12 hours and these LH pulses appeared in the same time window. We conclude that on Day 11 and Day 21 of pregnancy in gilts progesterone pulses do not follow an LH pulse within one hour. Further we demonstrated that the successful or not successful formation of a CL of pregnancy is independent of progesterone release on Day 11 after insemination. We confirmed the decline of progesterone from Day 11 to Day 21 in the vena cava caudalis and could demonstrate that this decline is partly due to lower progesterone pulse amplitude and frequency and that the decline occurs simultaneously with a decline in LH pulse amplitude.Peer reviewe

PTCOG Head and Neck Subcommittee Consensus Guidelines on Particle Therapy for the Management of Head and Neck Tumors

Purpose: Radiation therapy is a standard modality in the treatment for cancers of the head and neck, but is associated with significant short- and long-term side effects. Proton therapy, with its unique physical characteristics, can deliver less dose to normal tissues, resulting in fewer side effects. Proton therapy is currently being used for the treatment of head and neck cancer, with increasing clinical evidence supporting its use. However, barriers to wider adoption include access, cost, and the need for higher-level evidence.Methods: The clinical evidence for the use of proton therapy in the treatment of head and neck cancer are reviewed here, including indications, advantages, and challenges.Results: The Particle Therapy Cooperative Group Head and Neck Subcommittee task group provides consensus guidelines for the use of proton therapy for head and neck cancer.Conclusion: This report can be used as a guide for clinical use, to understand clinical trials, and to inform future research efforts.</p

Supraventricular cardiac conduction system exposure in breast cancer patients treated with radiotherapy and association with heart and cardiac chambers doses

Purpose: To assess sinoatrial node (SAN) and atrioventricular node (AVN) doses for breast cancer (BC) patients treated with 3D-CRT and evaluate whether “large” cardiac structures (whole heart and four cardiac chambers) would be relevant surrogates. Material and methods: This single center study was based on 116 BCE patients (56 left-sided, 60 right-sided) treated with 3D-CRT without respiratory gating strategies and few IMN irradiations from 2009 to 2013. The heart, the left and right ventricles (LV, RV), the left and right atria (LA, RA) were contoured using multi-atlases for auto-segmentation. The SAN and the AVN were manually delineated using a specific atlas. Based on regression analysis, the coefficients of determination (R2) were estimated to evaluate whether “large” cardiac structures were relevant surrogates (R2 > 0.70) of SAN and AVN doses. Results: For left-sided BC, mean doses were: 3.60 ± 2.28 Gy for heart, 0.47 ± 0.24 Gy for SAN and 0.74 ± 0.29 Gy for AVN. For right-sided BC, mean heart dose was 0.60 ± 0.25 Gy, mean SAN dose was 1.57 ± 0.63 Gy (>85 % of patients with SAN doses > 1 Gy) and mean AVN dose was 0.51 ± 0.14 Gy. Among all “large” cardiac structures, RA appeared as the best surrogate for SAN doses (R2 > 0.80). Regarding AVN doses, the RA may also be an interesting surrogate for left-sided BC (R2 = 0.78), but none of “large” cardiac structures appeared as relevant surrogates among right-sided BC (all R2 < 0.70), except the LA for patients with IMN (R2 = 0.83). Conclusions: In BC patients treated 10 years ago with 3D-CRT, SAN and AVN exposure was moderate but could exceed 1 Gy to the SAN in many right-sided patients with no IMN-inclusion. The RA appeared as an interesting surrogate for SAN exposure. Specific conduction nodes delineation remains necessary by using modern radiotherapy techniques

The Importance of Radiation Dose to the Atherosclerotic Plaque in the Left Anterior Descending Coronary Artery for Radiation-Induced Cardiac Toxicity of Breast Cancer Patients?

IMPORTANCE: Radiation-induced acute coronary events (ACEs) may occur as treatment-related late side effect of breast cancer (BC) radiation. However, the underlying mechanisms behind this radiation-induced cardiac disease remains to be determined. OBJECTIVE: The objective of this study was to test the hypothesis that radiation dose to calcified atherosclerotic plaques in the left anterior descending coronary artery (LAD) is a better predictor for ACEs than radiation dose to the whole heart or left ventricle in BC patients treated with radiotherapy (RT). DESIGN, SETTING, PARTICIPANTS, AND MAIN OUTCOMES AND MEASURES: The study cohort consisted of 910 BC patients treated with postoperative RT after breast conserving surgery. In total, 163 patients had an atherosclerotic plaque in the LAD. The endpoint was the occurrence of an ACE after treatment. For each individual patient, the mean heart dose (MHD), volume of the left ventricle receiving ≥ 5 Gy (LV-V5), mean LAD dose and mean dose to calcified atherosclerotic plaques in the LAD, if present, were acquired based on planning CT-scans. Cox-regression analysis was used to analyse the effects on the cumulative incidence of ACEs. RESULTS: The median follow-up time was 9.2 years (range: 0.1-14.3 years). In total, 38 patients (4.2%) developed an ACE during follow-up. For patients with an atherosclerotic plaque (n=163) the mean dose to the atherosclerotic plaque was the strongest predictor for ACE, even after correction for cardiovascular risk factors (HR: 1.269 (95% CI: 1.090-1.477), P=0.002). The LV-V5 was associated with ACEs in patients without atherosclerotic plaques in the LAD (n=680) (hazard ratio (HR): 1.021 (95% CI: 1.003-1.039; P=0.023). CONCLUSION AND RELEVANCE: The results of this study suggest that radiation dose to pre-existing calcified atherosclerotic plaques in the LAD is strongly associated with the development of ACEs in BC patients

Validation of separate multi-atlases for auto segmentation of cardiac substructures in CT-scans acquired in deep inspiration breath hold and free breathing

Background and purpose: Developing NTCP-models for cardiac complications after breast cancer (BC) radiotherapy requires cardiac dose-volume parameters for many patients. These can be obtained by using multi-atlas based automatic segmentation (MABAS) of cardiac structures in planning CT scans. We investigated the relevance of separate multi-atlases for deep inspiration breath hold (DIBH) and free breathing (FB) CT scans. Materials and methods: BC patients scanned in DIBH (n = 10) and in FB (n = 20) were selected to create separate multi-atlases consisting of expert panel delineations of the whole heart, atria and ventricles. The accuracy of atlas-generated contours was validated with expert delineations in independent datasets (n = 10 for DIBH and FB) and reported as Dice coefficients, contour distances and dose-volume differences in relation to interobserver variability of manual contours. Dependency of MABAS contouring accuracy on breathing technique was assessed by validation of a FB atlas in DIBH patients and vice versa (cross validation). Results: For all structures the FB and DIBH atlases resulted in Dice coefficients with their respective reference contours > 0.8 and average contour distances < 2 mm smaller than slice thickness of (CTs). No significant differences were found for dose-volume parameters in volumes receiving relevant dose levels (WH, LV and RV). Accuracy of the DIBH atlas was at least similar to, and for the ventricles better than, the interobserver variation in manual delineation. Cross-validation between breathing techniques showed a reduced MABAS performance. Conclusion: Multi-atlas accuracy was at least similar to interobserver delineation variation. Separate atlases for scans made in DIBH and FB could benefit atlas performance because accuracy depends on breathing technique

Impact of sarcopenia on survival and late toxicity in head and neck cancer patients treated with radiotherapy

Background and purpose: Sarcopenia is emerging as an adverse prognostic factor for survival and complication risk in cancer patients. This study aims to determine the impact of sarcopenia on survival and late toxicity in a large cohort of head and neck squamous cell carcinoma (HNSCC) patients treated with definitive (chemo)radiotherapy ((C)RT). Materials and methods: HNSCC patients treated with definitive (C)RT from January 2007 to June 2016 were included. Sarcopenia was assessed from radiation planning computed tomography (CT) scans using skeletal muscles at level C3. The impact of sarcopenia on overall survival (OS) and disease-free survival (DFS) was evaluated using the Kaplan–Meier method. Multivariable association models were developed to assess the impact of sarcopenia on late toxicity. Results: The study population was composed of 750 HNSCC patients. Cut-off values for sarcopenia were set at SMI < 42.4 cm2/m2 (men) and <30.6 cm2/m2 (women) corresponding lowest gender specific quartile. Sarcopenic patients had significantly poorer survival rates, especially those with lower performance status and locally advanced disease. In oropharyngeal cancer patients, survival was more determined by p16 status than by sarcopenia. In multivariable analysis, sarcopenia was associated with worse OS (HR 0.72, p = 0.012) and DFS (HR 0.67, p = 0.001). In multivariable association models, sarcopenia was associated with physician-rated xerostomia six months after treatment (OR 1.65, p = 0.027) and physician-rated dysphagia six and twelve months after treatment (OR 2.02, p = 0.012 and 2.51, p = 0.003, respectively). Conclusion: Sarcopenia in HNSCC patients receiving definitive (C)RT is an independent prognostic factor for worse survival outcomes and is associated with physician-rated toxicity

Network meta-analysis on the log-hazard scale, combining count and hazard ratio statistics accounting for multi-arm trials: a tutorial.

BACKGROUND: Data on survival endpoints are usually summarised using either hazard ratio, cumulative number of events, or median survival statistics. Network meta-analysis, an extension of traditional pairwise meta-analysis, is typically based on a single statistic. In this case, studies which do not report the chosen statistic are excluded from the analysis which may introduce bias. METHODS: In this paper we present a tutorial illustrating how network meta-analyses of survival endpoints can combine count and hazard ratio statistics in a single analysis on the hazard ratio scale. We also describe methods for accounting for the correlations in relative treatment effects (such as hazard ratios) that arise in trials with more than two arms. Combination of count and hazard ratio data in a single analysis is achieved by estimating the cumulative hazard for each trial arm reporting count data. Correlation in relative treatment effects in multi-arm trials is preserved by converting the relative treatment effect estimates (the hazard ratios) to arm-specific outcomes (hazards). RESULTS: A worked example of an analysis of mortality data in chronic obstructive pulmonary disease (COPD) is used to illustrate the methods. The data set and WinBUGS code for fixed and random effects models are provided. CONCLUSIONS: By incorporating all data presentations in a single analysis, we avoid the potential selection bias associated with conducting an analysis for a single statistic and the potential difficulties of interpretation, misleading results and loss of available treatment comparisons associated with conducting separate analyses for different summary statistics