Dosimetric advantages of generalised equivalent uniform dose-based optimisation on dose–volume objectives in intensity-modulated radiotherapy planning for bilateral breast cancer

Objective

We compared and evaluated the differences between two models for treating bilateral breast cancer (BBC): (i) dose–volume-based intensity-modulated radiation treatment (DV plan), and (ii) dose–volume-based intensity-modulated radiotherapy with generalised equivalent uniform dose-based optimisation (DV-gEUD plan).

Methods

The quality and performance of the DV plan and DV-gEUD plan using the Pinnacle³® system (Philips, Fitchburg, WI) were evaluated and compared in 10 patients with stage T2–T4 BBC. The plans were delivered on a Varian 21EX linear accelerator (Varian Medical Systems, Milpitas, CA) equipped with a Millennium 120 leaf multileaf collimator (Varian Medical Systems). The parameters analysed included the conformity index, homogeneity index, tumour control probability of the planning target volume (PTV), the volumes V_{20 Gy} and V_{30 Gy} of the organs at risk (OAR, including the heart and lungs), mean dose and the normal tissue complication probability.

Results

Both plans met the requirements for the coverage of PTV with similar conformity and homogeneity indices. However, the DV-gEUD plan had the advantage of dose sparing for OAR: the mean doses of the heart and lungs, lung V_{20 Gy}, and heart V_{30 Gy} in the DV-gEUD plan were lower than those in the DV plan (p<0.05).

Conclusions

A better result can be obtained by starting with a DV-generated plan and then improving it by adding gEUD-based improvements to reduce the number of iterations and to improve the optimum dose distribution.

Advances to knowledge

The DV-gEUD plan provided superior dosimetric results for treating BBC in terms of PTV coverage and OAR sparing than the DV plan, without sacrificing the homogeneity of dose distribution in the PTV.Breast cancer is the most common cancer and the leading cause of cancer deaths in females worldwide, with about 500 000 fatalities each year. In the USA and Europe, breast cancer constitutes, on average, one in four cancer cases among females [1,2]. Breast cancer among females in Asian countries mostly occurs between the ages of 40 and 50 years; however, in females in Western countries, it mostly occurs between the ages of 50 and 60 years [2,3].Bilateral breast cancer (BBC) is very rare, accounting for only 1–3% of all breast cancer cases [4-6]. Generally, no treatment guidelines exist for BBC. The treatment of BBC relies on surgery, chemotherapy and radiation therapy; additionally, BBC has previously demonstrated a poor prognosis. Current evidence indicates that the survival rate of patients with BBC is similar to that of patients with unilateral breast cancer [7,8]. The difficulty in treatment planning for BBC varies greatly, case by case, and is thus a great challenge for radiotherapy. Important issues have been raised concerning how to reduce the dose of radiation to normal tissues, how to maintain a certain tumour control probability (TCP) and how to improve the quality of life for patients with BBC.Most intensity-modulated radiotherapy (IMRT) planning systems apply dose–volume (DV)-based objective functions for dose optimisation, and an acceptable plan can be generated in most cases. For more complex plans, more iterations are required because many parameters need to be finely tuned. A successful improvement tool—the generalised equivalent uniform dose (gEUD)—was developed with fewer parameter settings [9-13] to improve the quality of plans. However, gEUD-based optimisation cannot demonstrate such advantages on the first run; more iterations are required to sculpt the dose distribution [14].To overcome the disadvantages mentioned above, we started with a DV-generated plan, and then improved it by adding gEUD-based improvements. The goal was to reduce the number of iterations and to improve the optimum dose distribution. This method first determined the approximate solutions for most of the treatment targets by DV-based optimisation, and then adjusted the DV histogram (DVH) by gEUD-based optimisation to obtain a superior solution. This study also compared and evaluated the differences between two different methods for the treatment of BBC—(i) a DV plan with DV-based optimisation (DV plan), and (ii) a DV-gEUD plan with mainly DV-based optimisation assisted by gEUD-based optimisation (DV-gEUD plan)—thus providing a quantitative indicator model for reference.     

Atypical diffusion-restricted lesion in 5-Fluorouracil encephalopathy

Central nervous system toxicity of 5-FU could show various manifestations, such as decreased alertness, disorientation, and agitation. It is generally accepted that lesions of 5-FU encephalopathy are mainly in the deep cerebral white matter and corpus callosum on MR imaging. Here we describe a case of 5-FU encephalopathy in gastric cancer with an atypical reversible diffusion-restricted lesion on MR imaging, showing bilateral basal ganglia, thalami, and parasagittal frontal cortex involvement on diffusion and T2-weighted imaging.     

Recommendations for personal respiratory protection in tuberculosis

These recommendations of the German Central Committee against Tuberculosis give an overview of the current scientific knowledge on the tuberculosis risk of health service employees and on the risk of infection in individual areas of work. The efficacy of face masks and their benefit in tuberculosis control is discussed. There are no reliable data on the efficacy of face masks in preventing infection with M. tuberculosis, nor can such data be expected in the near future, due to the complex interaction of infection-preventing measures. As rapid case finding, isolation, and immediate, effective treatment of infected patients already greatly diminish the risk of transmission, we consider face masks to be of limited use in reducing this risk. However, they may be beneficial in certain areas of work and in certain situations, particularly in the presence of elevated aerosol concentrations. The benefit of face masks depends largely on their correct application. The choice of a particular type of mask requires knowledge of the current epidemiological situation, and a competent assessment of the risk in the area of work for which it is chosen, taking into account the closeness of contact with potentially infectious tuberculosis patients.     

Chronic insomnia is associated with a shift of interleukin-6 and tumor necrosis factor secretion from nighttime to daytime

Chronic insomnia, by far the most commonly encountered sleep disorder in medical practice, is characterized by difficulty falling or staying asleep at night and increased fatigue during the day. Interleukin-6 (IL-6) and tumor necrosis factor (TNF) are fatigue-inducing cytokines, and the daytime secretion of IL-6 is negatively influenced by the quantity and quality of the previous night's sleep. We hypothesize that the poor quality of insomniacs' sleep is associated with a hypersecretion of these 2 cytokines during the daytime, which, in turn, correlates with the fatigue experienced by these patients. Eleven young insomniacs (6 men and 5 women) and 11 (8 men and 3 women) age- and body mass index (BMI)-matched healthy controls participated in the study. Subjects were recorded in the sleep laboratory for 4 consecutive nights and serial 24-hour plasma measures of IL-6 and TNF were obtained during the 4th day. Insomniacs compared to controls slept poorly (sleep latency and wake were increased, whereas percentage sleep time was decreased during baseline nights, all P <.05). The mean 24-hour IL-6 and TNF secretions were not different between insomniacs and controls. However, the difference in the change (increase) of IL-6 plasma levels from midafternoon (2 PM) to evening (9 PM) between insomniacs and controls was significant (P <.01). Furthermore, cosinor analysis showed a significant shift of the major peak of IL-6 secretion from nighttime (4 AM) to evening (7 PM) in insomniacs compared to controls (P <.05). Also, while TNF secretion in controls showed a distinct circadian rhythm with a peak close and prior to the offset of sleep (P <.05), such a rhythm was not present in insomniacs. Finally, daytime secretion of TNF in insomniacs was characterized by a regular rhythm of 4 hours (P <.05); such a distinct periodicity was not present in controls. We conclude that chronic insomnia is associated with a shift of IL-6 and TNF secretion from nighttime to daytime, which may explain the daytime fatigue and performance decrements associated with this disorder. The daytime shift of IL-6 and TNF secretion, combined with a 24-hour hypersecretion of cortisol, an arousal hormone, may explain the insomniacs' daytime fatigue and difficulty falling asleep.     

Cardiorespiratory fitness and the progression of carotid atherosclerosis in middle-aged men

BACKGROUND: Good cardiorespiratory fitness has been associated with reduced risk for clinical events of atherosclerotic vascular diseases, but whether it is related to slower progression of early atherosclerosis is unclear. OBJECTIVE: To study the association between cardiorespiratory fitness and the progression of early carotid atherosclerosis. DESIGN: 4-year follow-up study. SETTING: Eastem Finland. PARTICIPANTS: Population-based sample of 854 men 42 to 60 years of age. MEASUREMENTS: Maximal oxygen uptake (VO2max [mL/kg per minute]) was measured directly by using respiratory gas exchange in a cycle ergometer exercise test. Carotid atherosclerosis was assessed by using B-mode ultrasonography. RESULTS: After adjustments for age, technical covariates, and cigarette smoking, VO2max had strong, inverse, and graded associations with 4-year increases in maximal intima-media thickness (IMT) (standardized regression coefficient beta = -0.120; P = 0.002), plaque height (beta = -0.140; P < 0.001), surface roughness (beta = -0.147; P < 0.001), and mean IMT (beta = -0.080; P = 0.035). These associations weakened but remained statistically significant after additional adjustment for systolic blood pressure, serum levels of apolipoprotein B, diabetes, and plasma fibrinogen levels. The increases in maximal IMT, surface roughness, and mean IMT (23%, 31%, and 100%, respectively) were larger among men in the lowest quartile of VO2max (<26.1 mL/kg per minute) than among those in the highest quartile (>36.2 mL/kg per minute). CONCLUSIONS: Good cardiorespiratory fitness is associated with slower progression of early atherosclerosis in middle-aged men. These findings are important because they emphasize that middle-aged men can be evaluated for cardiorespiratory fitness to estimate their future risk for atherosclerotic vascular diseases. Additional research is warranted to investigate a possible causal relationship between cardiorespiratory fitness and atherosclerosis.     

Impact of comorbidity on perioperative mortality after radical cystectomy

The TNM classification integrates the currently valid prognostic factors for tumour-specific survival after radical cystectomy due to bladder cancer. But it does not contain the most important criteria for general survival. We assessed the preoperative and operative aspects of our patients between 1992 and 2007 concerning the early mortality within the hospital stay or within 30 days after surgery. 3% of our 404 patients died within these periods, which is equivalent to the results of other contemporary publications. Except for the comorbidity of the patients, none of the included parameters (initial symptoms, histology, indication for cystectomy, AJCC stadium, year of surgery, durance of surgery, surgeon, concomitant interventions, type of urinary diversion, blood loss and number of transfusions) showed a significant correlation to cause or postoperative time of death. For the preoperative assessment of the health of the patient a multidisciplinary cooperation of urology, anaesthesia and general and/or internal medicine is necessary. In the era of evidence-based medicine the personal judgement of the evaluating physician is not sufficient. Instead a validated index should be used to help one to obtain an objective evaluation of the risks. The ACE-27 (Adult Comorbidity Evaluation-27) provides such a validated assistance in the assessment of the comorbidity of patients and therefore possible mortality after radical cystectomy.     

New England Medical Center Posterior Circulation Stroke Registry: I. Methods, Data Base, Distribution of Brain Lesions, Stroke Mechanisms, and Outcomes

Among 407 New England Medical Center Posterior Circulation Registry (NEMC-PCR) patients, 59% had strokes without transient ischemic attacks (TIAs), 24% had TIAs before strokes, and 16% had only posterior circulation TIAs. Embolism was the commonest stroke mechanism accounting for 40% of cases (24% cardiac origin, 14% arterial origin, 2% had potential cardiac and arterial sources). In 32%, large artery occlusive lesions caused hemodynamic brain infarction. Stroke mechanisms in the posterior and anterior circulation are very similar. Infarcts most often included the distal posterior circulation territory (rostral brainstem, superior cerebellum and occipital and temporal lobes), while the proximal (medulla and posterior inferior cerebellum) and middle (pons and anterior inferior cerebellum) territories were equally involved. Infarcts that included the distal territory were twice as common as those that included the proximal or middle territories. Most distal territory infarcts were attributable to embolism. Thirty day mortality was low (3.6%). Embolic stroke mechanism, distal territory location, and basilar artery occlusive disease conveyed the worst prognosis.     

New England Medical Center Posterior Circulation Stroke Registry II. Vascular Lesions

Among 407 New England Medical Center Posterior Circulation Registry (NEMC-PCR) patients, the extracranial (ECVA) and intracranial vertebral arteries (ICVA) were the commonest sites of severe occlusive disease followed by the basilar artery (BA). Severe occlusive lesions were found in >1 large artery in 148 patients; 134 had unilateral or bilateral severe disease at one arterial location. Single arterial site occlusive disease occurred most often in the ECVA (52 patients, 15 bilateral) followed by the ICVA (40 patients, 12 bilateral) and the BA (46 patients). Involvement of the ICVAs and the BA was very common and some patients also had ECVA lesions. Hypertension, smoking, and coronary and peripheral vascular disease were most prevalent in patients with extracranial disease while diabetes and hyperlipidemia were more common when occlusive lesions were only intracranial. Intra-arterial embolism was the most common mechanism of brain infarction in patients with ECVA and ICVA occlusive disease. ICVA occlusive lesions infrequently caused infarction limited to the proximal territory (medulla and posterior inferior cerebellum). BA lesions most often caused infarcts limited to the middle posterior circulation territory (pons and anterior inferior cerebellum). Posterior cerebral artery occlusive lesions were predominantly embolic. Penetrating artery disease caused mostly pontine and thalamic infarcts. Prognosis was poorest in patients with BA disease. The best prognosis surprisingly was in patients who had multiple arterial occlusive lesions; they often had position-sensitive transient ischemic attacks during months or years.     

Comparison of clinical outcomes and spectral Doppler indices of uterine and ovarian stromal arteries in women undergoing myomectomy with or without hypogastric arterial ligation.

OBJECTIVE: To compare clinical outcomes and hemodynamic alterations of uterine and ovarian stromal arteries between patients with symptomatic myomas undergoing myomectomy preceded by arterial ligation and those undergoing myomectomy alone. METHODS: In this prospective, non-randomized comparative study, myomectomy was performed on 69 women with symptomatic myomas. Myomectomy alone was performed in 31 patients (Group I) and myomectomy with concomitant bilateral hypogastric arterial ligation was performed in 38 patients (Group II). In both groups, surgical results and clinical outcomes were evaluated by peripheral hemoglobin levels, a pictorial blood-loss assessment chart, and visual analog scales. Spectral Doppler indices of uterine and ovarian stromal arteries, including peak systolic velocity, end-diastolic velocity, pulsatility index and resistance index were performed preoperatively, and 1 day and 1 or more months postoperatively. RESULTS: Twenty-two patients in Group I and 31 patients in Group II received regular follow-up examinations for a mean follow-up period of 10.1 months. Menstrual flow, dysmenorrhea and hemoglobin levels improved significantly after surgery in both groups. Blood loss during surgery was less in Group II than it was in Group I (P=0.02). Doppler indices of uterine and ovarian stromal arteries from preoperation to mean follow-up point were not significantly different between the groups, except for a significantly lower uterine artery pulsatility index in Group II (P=0.01). CONCLUSIONS: Myomectomy with hypogastric arterial ligation for symptomatic myomas is as efficient as is myomectomy alone and reduces blood loss during surgery. Serial Doppler studies showed that hypogastric ligation does not block uterine and ovarian perfusion, and even reduces the impedance of the uterine arteries. The long-term recurrence rate after myomectomy with hypogastric arterial ligation remains to be determined.