Citations

Purpose Despite increasing awareness of accrual challenges, it is unknown if accrual of older patients to breast cancer treatment trials is improving. Methods We examined accrual of older patients to Alliance for Clinical Trials in Oncology systemic therapy breast cancer trials during 1985-2012 and compared disease characteristics and reasons for therapy cessation for older (age ≥ 65 years and ≥ 70 years) versus younger (age < 65 years and < 70 years) participants. To examine accrual trends, we modeled age as a function of time, using logistic regression. Results Overall, 17% of study participants were ≥ 65 years of age. Approximately 15%, 24%, and 24% of participants in adjuvant, neoadjuvant, and metastatic trials were age ≥ 65 years, and 7%, 15%, and 13% were age ≥ 70 years, respectively. The odds of a patient age ≥ 65 years enrolling significantly increased over time for adjuvant trials (odds ratio [OR] per year, 1.04; 95% CI, 1.04 to 1.05) but decreased significantly for neoadjuvant and metastatic trials (OR, 0.62; 95% CI, 0.58 to 0.67 and OR, 0.98, 95% CI, 0.97 to 1.00). Similar trends were seen for those age ≥ 70 years but these were statistically significant for adjuvant and neoadjuvant trials only (OR, 1.05, 95% CI, 1.04 to 1.07; and OR, 0.57, 95% CI, 0.52 to 0.62). In general, those age ≥ 65 years ( v those < 65 years) in adjuvant studies had a higher mean number of lymph nodes involved and more hormone receptor-negative tumors, although tumor sizes were similar. Early protocol treatment cessation was also more frequent in those age ≥ 65 years (50%) versus < 65 years (35.9%) across trials. Conclusion Older patients with breast cancer remain largely underrepresented in cooperative group therapeutic trials. We observed some improvement in accrual to adjuvant trials but worsening of accrual for neoadjuvant/metastatic trials. Novel strategies to increase accrual of older patients are critical to meaningfully change the evidence base for this growing patient population.

75 Background: Combined radiotherapy (RT) and long-term hormonal therapy (HT) is a standard treatment option for high-risk prostate cancer. Dose escalated RT alone has been shown to improve disease free survival. Increased sensitivity of prostate cancer to high doses per fraction has led to hypofractionation as a method to radiobiologically escalate dose.We report on the quality of life of patients treated with combined hypofractionated RT and HT. Methods: A prospective phase I/II study enrolling patients with any of: clinical T3, PSA ≥20, or Gleason 8-10. Forty-five Gy (1.8 Gy/fraction) was delivered to the pelvic nodes with a concomitant 22.5 Gy intensity-modulated RT boost to the prostate, for a total of 67.5 Gy (2.7 Gy/fraction) in 25 fractions over 5 weeks. Hormonal therapy was administered for 2-3 years. Patient reported outcomes were measured at baseline and every 6 months using the validated Expanded Prostate Cancer Index Composite (EPIC) questionnaire, which measures urinary, bowel, sexual, and hormonal domains. Results: Sixty patients with a minimum 24 months of patient-reported outcomes were analyzed. Mean scores comparing baseline to 24 month values are reported. There were no statistically significant changes in the urinary summary scores (86.3 vs. 86.0, p=0.45) or any of the urinary subscales (function, bother, incontinence, irritative/obstructive). Domain summary score decreases were observed in: bowel by 4.4% (94.7 vs. 90.3, p<0.01), sexual by 27% (44.5 vs. 17.5, p<0.01), and hormonal by 11.9% (93.1 vs. 81.2, p<0.01). Examining time trends in outcomes, most changes occurred within the first 6 months with smaller changes thereafter. Conclusions: Hypofractionated RT combined with long-term HT is associated with good patient-reported urinary and bowel outcomes at 24 months. Sexual and hormonal summary scores are affected, largely due to continued androgen deprivation therapy. Further follow-up is needed to document patient reported outcomes after testosterone recovery. No significant financial relationships to disclose.

Blast traumatic brain injury (bTBI) may happen due to sudden blast and high-frequency loads. Due to the moral issues and the burden of experimental approaches, using computational methods such as finite element analysis (FEA) can be effective. Several finite element studies have focused on the effects of TBI to anticipate and understand the brain dynamic response. One of the most important factors in every FEA study of bTBI is the accurate modeling of brain tissue material properties. The main goal of this study is a comparison of different brain tissue constitutive models to understand the dynamic response of brain under an identical blast load. The multi-material FE modeling of the human head has several limitations such as its complexity and consequently high computational costs. Therefore, a spherical head model is modeled which suggests more straightforward observation/understanding of the FE modeling of skull (solid), CSF (fluid), and the brain tissue. Three different material models are considered for the brain tissue, namely hyperelastic, viscoelastic, and hyperviscoelastic. Brain dynamic responses are studied in terms of the head kinematics (linear acceleration), intracranial pressure (ICP), shear stress, and maximum mechanical strain. Our results showed that the hyperelastic model predicts larger ICP and shear than other constitutive brain tissue models. However, all material models predicted similar shear strain and head accelerations.

Skull deformation and vibration has been hypothesized to be an injury mechanism when the human head undergoes an impact scenario. The extent that skull deformation may increase the risk of traumatic brain injury, however, is not well understood. This computational study explains whether skull deformation has any impact on the variation of intracranial pressure (ICP). To this end, a finite element head model including major anatomical components of the human head was employed. The head model has been validated against ICP variations on the brain. The impact simulations were carried out using a rigid cylindrical impactor. The scenarios were frontal impacts with the impactor hitting the forehead of the head model at two impact severity levels. In order to examine the effect of skull elasticity on the stress wave propagation inside the cranium under an external applied force, the skull was also taken as a rigid body with the same density as the elastic one, and the result were compared with those obtained with the deformable skull. For the two cases, the variation of ICPs at the coup and countercoup sites were recorded and compared. The results of the study showed that, for the case studies presented here, the deformation of skull didn’t increase the level of ICP inside the brain. It was concluded that the skull rapid body motion might be responsible for brain injuries.

Blast-induced traumatic brain injury (bTBI), is defined as a type of acquired brain injury that occurs upon the interaction of the human head with blast-generated high-pressure shockwaves. Lack of experimental studies due to moral issues, have motivated the researchers to employ computational methods to study the bTBI mechanisms. Accordingly, a nonlinear finite element (FE) analysis was employed to study the interaction of both unprotected and protected head models with explosion pressure waves. The head was exposed to the incoming shockwaves from front, back, and side directions. The main goal was to examine the effects of head protection tools and the direction of blast waves on the tissue and kinematical responses of the brain. Generation, propagation, and interactions of blast waves with the head were modeled using an arbitrary Lagrangian-Eulerian (ALE) method and a fluid-structure interaction (FSI) coupling algorithm. The FE simulations were performed using Ls-Dyna, a transient, nonlinear FE code. Side blast predicted the highest mechanical responses for the brain. Moreover, the protection assemblies showed to significantly alter the blast flow mechanics. Use of faceshield was also observed to be highly effective in the front blast due to hindering of shockwaves.

Objectives This study evaluated our experience after implementing a pelvic floor rehabilitation program including behavioral modification, biofeedback, and vaginal electrogalvanic stimulation (EGS). Methods This prospective cohort study evaluated outcomes of patients with pelvic floor dysfunction (urinary or defecatory dysfunction, pelvic pain/dyspareunia) who underwent pelvic floor rehabilitation. Patients received 4 to 7 sessions (1 every 2 weeks) including biofeedback and concluded with 30 minutes of vaginal EGS. Surveys assessed subjective changes in symptoms; success was evaluated using a 10-point visual analog scale (VAS) at the final session (10 = most successful). Paired comparisons of responses at baseline and final treatment were evaluated. Results Ninety-four patients were followed up through therapy completion. Treatment indications included urinary (89.4%), defecatory (33.0%), and pelvic pain or dyspareunia (30.9%); 44.7% of patients had a combination of indications. Among women with urinary symptoms, the percentage reporting leakage decreased from 92.9% to 79.3% (P = 0.001), leakage at least daily decreased from 69.0% to 39.5% (P < 0.001), daily urgency with leakage decreased from 42.7% to 19.5% (P = 0.001), daily urgency without leakage decreased from 41.5% to 18.3% (P < 0.001), and median VAS rating (0 = not at all, 10 = a great deal) of daily life interference decreased from 5 to 1.5 (P < 0.001). The median success ratings were 8, 8, and 7 for treatment of urinary symptoms, pelvic pain/dyspareunia, and bowel symptoms, respectively. Conclusions An aggressive pelvic rehabilitation program including biofeedback with vaginal EGS had a high rate of self-reported subjective success and satisfaction and should be considered a nonsurgical treatment option in patients with pelvic floor dysfunction.

It has long been known that aging, at both the cellular and organismal levels, contributes to the development and progression of the pathology of many chronic diseases. However, much less research has examined the inverse relationship—the contribution of chronic diseases and their treatments to the progression of aging‐related phenotypes. Here, we discuss the impact of three chronic diseases (cancer, HIV/AIDS, and diabetes) and their treatments on aging, putative mechanisms by which these effects are mediated, and the open questions and future research directions required to understand the relationships between these diseases and aging.

Hypertensive pregnancy (HTNP) is a risk factor for future cardiovascular disease. Exaggerated cardiovascular responses to physical stress are also considered an independent marker of cardiovascular disease risk. However, there are limited data regarding the blood pressure (BP) responses to acute stress in women, who have a history of HTNP. Hence, the aim of the study is to compare BP responses to a physical stress in postmenopausal women with a history of HTNP to age- and parity-matched women with a history of normotensive pregnancy (NP). Beat-to-beat BP and heart rate was recorded in 64 postmenopausal women with [age = 58.5 (55.2, 62.2) yr, where values are the median, 25th percentile, and 75th percentile] and without [age = 59.4 (55.9, 62.4) yr] a history of HTNP before and during isometric handgrip (IHG) exercise (30% of maximal voluntary contraction) to fatigue. Muscle metaboreflex was measured during postexercise ischemia following IHG exercise. BP variables increased similarly in response to IHG exercise [systolic: NP = 11.5 (8.9, 17.6) %, HTNP = 11.3 (9.5, 15.9) %; diastolic NP = 11.2 (7.9, 13.3) %, HTNP = 9.5 (7.1, 14.3) %; mean blood pressure: NP = 9.8 (5.0, 13.6) %, and HTNP = 7.2 (4.4, 10.4) %] and postexercise ischemia [systolic: NP = 14.1 (10.3, 23.0) %, HTNP = 15.8 (10.6, 21.4) %; diastolic NP = 12.2 (4.8, 17.0) %, HTNP = 10.4 (5.3, 17.1) %; and mean blood pressure: NP = 11.1 (6.1, 17.9) %, HTNP = 9.4 (2.9, 14.8) %] in both groups. Although having a history of HTNP is associated with future cardiovascular disease risk, results from this study suggest that the risk may not be manifested through altered cardiovascular metaboreflex response to physical stressors.

Central (aortic) blood pressure, arterial stiffness, and sympathetic nerve activity increase with age in women. However, it is unknown if the age-related increase in sympathetic activity influences aortic hemodynamics and carotid-femoral pulse wave velocity (cfPWV), an index of central aortic stiffness. The goal of this study was to determine if aortic hemodynamics and cfPWV are directly influenced by sympathetic nerve activity by measuring aortic hemodynamics, cfPWV, and muscle sympathetic nerve activity (MSNA) in women before and during autonomic ganglionic blockade with trimethaphan camsylate. We studied 12 young premenopausal (23 ± 4 yr) and 12 older postmenopausal (57 ± 3 yr) women. These women did not differ in body mass index or mean arterial pressure ( P > 0.05 for both). At baseline, postmenopausal women had higher aortic pulse pressure, augmented pressure, augmentation index adjusted for a heart rate of 75 beats/min, wasted left ventricular pressure energy, and cfPWV than young women ( P < 0.05). During ganglionic blockade, postmenopausal women had a greater decrease in these variables in comparison to young women ( P < 0.05). Additionally, baseline MSNA was negatively correlated with the reductions in aortic pulse pressure, augmented pressure, and wasted left ventricular pressure energy during ganglionic blockade in postmenopausal women ( P < 0.05) but not young women. Baseline MSNA was not correlated with the changes in augmentation index adjusted for a heart rate of 75 beats/min or cfPWV in either group ( P > 0.05 for all). Our results suggest that some aortic hemodynamic parameters are influenced by sympathetic activity to a greater extent in older postmenopausal women than in young premenopausal women.NEW & NOTEWORTHY Autonomic ganglionic blockade results in significant decreases in multiple aortic pulse wave characteristics (e.g., augmented pressure) and central pulse wave velocity in older postmenopausal women but not in young premenopausal women. Certain aortic pulse wave parameters are negatively influenced by sympathetic activity to a greater extent in older postmenopausal women.