Review of clinical brachytherapy uncertainties: Analysis guidelines of GEC-ESTRO and the AAPM

Background and purpose

A substantial reduction of uncertainties in clinical brachytherapy should result in improved outcome in terms of increased local control and reduced side effects. Types of uncertainties have to be identified, grouped, and quantified.

Methods

A detailed literature review was performed to identify uncertainty components and their relative importance to the combined overall uncertainty.

Results

Very few components (e.g., source strength and afterloader timer) are independent of clinical disease site and location of administered dose. While the influence of medium on dose calculation can be substantial for low energy sources or non-deeply seated implants, the influence of medium is of minor importance for high-energy sources in the pelvic region. The level of uncertainties due to target, organ, applicator, and/or source movement in relation to the geometry assumed for treatment planning is highly dependent on fractionation and the level of image guided adaptive treatment. Most studies to date report the results in a manner that allows no direct reproduction and further comparison with other studies. Often, no distinction is made between variations, uncertainties, and errors or mistakes. The literature review facilitated the drafting of recommendations for uniform uncertainty reporting in clinical BT, which are also provided. The recommended comprehensive uncertainty investigations are key to obtain a general impression of uncertainties, and may help to identify elements of the brachytherapy treatment process that need improvement in terms of diminishing their dosimetric uncertainties. It is recommended to present data on the analyzed parameters (distance shifts, volume changes, source or applicator position, etc.), and also their influence on absorbed dose for clinically-relevant dose parameters (e.g., target parameters such as D₉₀ or OAR doses). Publications on brachytherapy should include a statement of total dose uncertainty for the entire treatment course, taking into account the fractionation schedule and level of image guidance for adaptation.

Conclusions

This report on brachytherapy clinical uncertainties represents a working project developed by the Brachytherapy Physics Quality Assurances System (BRAPHYQS) subcommittee to the Physics Committee within GEC-ESTRO. Further, this report has been reviewed and approved by the American Association of Physicists in Medicine.     

A meta-analytic approach to estimating nocebo effects in neuropathic pain trials

The development of non-specific adverse effects following the administration of an active or inert substance is referred to as nocebo phenomenon. We aimed to estimate the frequency and severity of nocebo responses in clinical trials of pharmacological treatments for neuropathic pain. A systematic Medline search for all randomized, placebo-controlled neuropathic pain trials published between 2000 and 2010 was carried out. Meta-analysis of the frequency of nocebo responses was performed by pooling the percentage of placebo-treated patients that exhibited drug-related adverse events. Nocebo severity was calculated from the percentage of placebo-treated patients that dropped out due to drug-related adverse events. The pooled frequency of nocebo responses in neuropathic pain trials was 52.0% (95% CI: 35.7–67.9) and the pooled nocebo severity was 6.0% (95% CI: 4.5–8.0). Meta-regression analysis revealed an association between the frequency of nocebo responses and the percentage of females in the placebo-treated group (p = 0.0028). Furthermore, nocebo severity displayed a significant association with the study population (p = 0.0386). Our data indicates a powerful nocebo effect in neuropathic pain trials that may be influenced by gender- and population-related factors. A strong nocebo effect may be adversely affecting adherence and efficacy of current treatments for neuropathic pain in clinical practice.     

Cover Picture: Eur. J. Immunol. 2/12

The cover is based on a spinal cord histology section taken from a TNFR2^?/? mouse adoptively transferred with TNFR2^?/? Treg cells prior to immunization with MOG_35–55 to induce EAE. The section is stained with Luxol Fast blue to detect demyelination; Luxol Fast Red, which detects inflammatory infiltration, is the counterstain. The image is taken from the article by Tsakiri et al. (pp. 403–412) in which it is shown that TNFR2 on non‐haematopoietic cells is necessary for Treg‐cell suppressive activity and repression of EAE development. The colour of the image has been digitally altered for the cover.     

Ex vivo and in vivo coronary ostial locations in humans

Purpose  

Knowledge of the normal in vivo distribution and variation of coronary ostial locations is essential in the planning of various interventional and surgical procedures. However, all studies to date have reported the distribution of coronary ostia locations only in cadaver hearts. In this study, we sought to assess the distribution of coronary ostial locations in patients using cardiac dual-source computed tomography (CT) and compare these values to those of human cadaveric specimens.     

Red blood cell distribution width in elderly hospitalized patients with cardiovascular disease

BACKGROUNDRed blood cell distribution width (RDW) is elevated in patients with cardiovascular disease (CVD).AIMTo determine RDW values and impact of CV and non-CV coexisting morbidities in elderly patients hospitalized with chronic CVD.METHODSThis prospective study included 204 consecutive elderly patients (age 77.5 [7.41] years, female 94 [46%], left ventricular ejection fraction 53.00% [37.50, 55.00]) hospitalized with chronic CVD at the Cardiology Department of Larissa University General Hospital (Larissa, Greece) from January 2019 to April 2019. Elderly patients were selected due to the high prevalence of coexisting morbidities in this patient population. Hospitalized patients with acute CVD (acute coronary syndromes, new-onset heart failure [HF], and acute pericarditis/myocarditis), primary isolated valvular heart disease, sepsis, and those with a history of blood transfusions or cancer were excluded. The evaluation of the patients within 24 h from admission included clinical examination, laboratory blood tests, and echocardiography.RESULTSThe most common cardiac morbidities were hypertension and coronary artery disease, with acutely decompensated chronic heart failure (ADCHF) and atrial fibrillation (AF) also frequently being present. The most common non-cardiac morbidities were anemia and chronic kidney disease followed by diabetes mellitus, chronic obstructive pulmonary disease, and sleep apnea. RDW was significantly elevated 15.48 (2.15); 121 (59.3%) of patients had RDW > 14.5% which represents the upper limit of normal in our institution. Factors associated with RDW in stepwise regression analysis were ADCHF (coefficient: 1.406; 95% confidence interval [CI]: 0.830-1.981; P < 0.001), AF (1.192; 0.673 to 1.711; P < 0.001), and anemia (0.806; 0.256 to 1.355; P = 0.004). ADCHF was the most significant factor associated with RDW. RDW was on average 1.41 higher for patients with than without ADCHF, 1.19 higher for patients with than without AF, and 0.81 higher for patients with than without anemia. When patients were grouped based on the presence or absence of anemia, ADCHF and AF, heart rate was not increased in those with anemia but was significantly increased in those with ADCHF or AF.CONCLUSIONRDW was elevated in elderly hospitalized patients with chronic CVD. Factors associated with RDW were anemia and CV factors associated with elevated heart rate (ADCHF, AF), suggesting sympathetic overactivity.