Towards an objective evaluation of tolerances for beam modeling in a treatment planning system

The performance of a convolution/superposition based treatment planning system depends on the ability of the dose calculation algorithm to accurately account for physical interactions taking place in the tissue, key components of the linac head and on the accuracy of the photon beam model. Generally the user has little or no control over the performance of the dose calculation algorithm but is responsible for the accuracy of the beam model within the constraints imposed by the system. This study explores the dosimetric impact of limitations in photon beam modeling accuracy on complex 3D clinical treatment plans. A total of 70 photon beam models was created in the Pinnacle treatment planning system. Two of the models served as references for 6 MV and 15 MV beams, while the rest were created by perturbing the reference models in order to produce specific deviations in specific regions of the calculated dose profiles (central axis and transverse). The beam models were then used to generate 3D plans on seven CT data sets each for four different treatment sites (breast and conformal prostate, lung and brain). The equivalent uniform doses (EUD) of the targets and the principal organs at risk (OARs) of all plans ( approximately 1000) were calculated and compared to the EUDs delivered by the reference beam models. In general, accurate dosimetry of the target is most greatly compromised by poor modeling of the central axis depth dose and the horns, while the EUDs of the OARs exhibited the greatest sensitivity to beam width accuracy. Based on the results of this analysis we suggest a set of tolerances to be met during commissioning of the beam models in a treatment planning system that are consistent in terms of clinical outcomes as predicted by the EUD.     

Patents related to the treatment and diagnosis of bruxism

Introduction: Bruxism is among the most chronic dental problems worldwide, and its perception may increase indicatively the condition of people’s health, avoiding future health problems. Technologic solutions have improved considerably owing to new diagnostic and treatment technologies and their automation. This review aims to assess therapeutic methods for bruxism through analysis of patent applications spanning recent decades.

Areas covered: Patent families of bruxism, and products available on the market. Data were obtained through Questel Orbit from the European Patent Office on a worldwide basis using Cooperative Patent Classification (CPC), analyzing 134 patent families. The products on the market were mapped and classified as used for diagnosis, treatment, or both.

Expert opinion: This technological prospect has shown that the technological field of bruxism is growing toward smaller, automated devices; there is still no predominant owner of the technologies. Products are expected to provide home use with a high degree of reliability and specificity, using the Internet of Things (telemedicine associated with industry 4.0) and enabling real-time diagnosis.     

Primary Gleason Grade 4 at the Positive Margin Is Associated with Metastasis and Death Among Patients with Gleason 7 Prostate Cancer Undergoing Radical Prostatectomy

Background

The presence of a positive surgical margin (PSM) at radical prostatectomy (RP) has been linked to an increased risk of biochemical recurrence and receipt of secondary therapy; however, its association with other oncologic end points remains controversial.

Objective

To evaluate the association of primary Gleason grade (GG) at the site of PSM with subsequent clinical progression and mortality among patients with Gleason score (GS) 7 prostate cancer (PCa).

Design, setting, and participants

We identified 1036 patients who underwent RP between 1996 and 2002. A single uropathologist re-reviewed all specimens noted to have a PSM to record GG at the margin.

Outcome measurements and statistical analysis

Survival was estimated using the Kaplan-Meier method. Cox models were used to analyze the association of margin primary GG with outcome.

Results and limitations

Overall, 338 men (33%) had a PSM; of those, 242 had PSM GG3 and 96 had PSM GG4. Median postoperative follow-up was 13 yr. Compared with men with PSM GG3 or a negative SM, we noted that men with PSM GG4 had significantly worse 15-yr systemic progression-free survival (74% vs 90% vs 93%, respectively; p < 0.001) and cancer-specific survival (86% vs 96% vs 97%, respectively; p = 0.002). On multivariable analysis, the presence of PSM GG4 was associated with increased risks of systemic progression (hazard ratio [HR]: 2.77; p = 0.003) and death from PCa (HR: 3.93; p = 0.02) among men with a PSM. Limitations include the relatively small rate of disease recurrence.

Conclusions

PSM primary GG4 was independently associated with adverse oncologic outcomes among men with GS7 PCa. Pending external validation, GG at the PSM may be considered for inclusion in pathologic reports and risk stratification following RP.

Patient summary

Among patients with Gleason grade 7 prostate cancer and a positive surgical margin at the time of prostatectomy, we found that higher Gleason grade at the margin was associated with worse oncologic outcomes.     

The presence of extracapsular extension is associated with an increased risk of death from prostate cancer after radical prostatectomy for patients with seminal vesicle invasion and negative lymph nodes

ObjectivesDetermining clinicopathologic features that stratify the risk of disease progression in patients with seminal vesicle invasion at radical prostatectomy remains critical for patient counseling, clinical trial enrollment, and the judicious application of secondary therapies. Then, we evaluated the prognostic significance of concomitant extracapsular extension (ECE) in patients with seminal vesicle invasion and negative lymph nodes at radical prostatectomy.MethodsWe identified 1,132 patients who underwent prostatectomy between 1987 and 2009 and were found to have pT3bN0 disease. Median postoperative follow-up was 10.6 years (interquartile range, 5.9–15.3). Survival was estimated using the Kaplan-Meier method and compared for patients with and without ECE with the log-rank test. The association of ECE with outcome was evaluated using Cox proportional hazards regression models.ResultsA total of 693 (61%) patients were noted to have ECE. Compared with pT3bN0 patients without ECE, patients with pT3bN0 tumors and ECE had a significantly worse 15-year biochemical recurrence-free survival (29% vs. 39%; P<0.001), systemic progression-free survival (71% vs. 81%; P<0.001), cancer-specific survival (80% vs. 89%; P<0.001), and overall survival (50% vs. 63%; P<0.001). On multivariate analysis, the presence of ECE was associated with significantly increased risks of systemic progression (hazard ratio [HR], 1.56; P=0.006), death from prostate cancer (HR, 1.71; P=0.01), and all-cause mortality (HR, 1.35; P=0.007). Meanwhile, adjuvant hormonal therapy, which was received by 334 patients (29.5%), was associated with significantly decreased risks of systemic progression (HR, 0.50; P=0.0004) and cancer death (HR, 0.57; P=0.03), but not all-cause mortality (HR, 0.81; P=0.09). Limitations included retrospective design and nonstandardized application of secondary treatments.ConclusionsThe presence of ECE in patients with pT3bN0 prostate cancer is associated with increased risks of systemic progression and cancer death. Pending validation, ECE may be incorporated into risk stratification or staging classification or both. Meanwhile, these patients continue to represent ideal candidates for adjuvant therapy trials.     

Living donor liver transplantation in children: Should the adult donor be operated on by an adult or pediatric surgeon? Experience of a single pediatric center

Background/Purpose

Living donor liver transplantation has become a cornerstone for the treatment of children with end-stage hepatic dysfunction, especially within populations or countries with low rates of organ utilization from deceased donors. The objective is to report our experience with 185 living donors operated on by a team pediatric surgeons in a tertiary center for pediatric liver transplantation.

Methods

Retrospective analysis of medical records of donors of hepatic grafts for transplant undergoing surgery between June 1998 and March 2013.

Results

Over the last 14 years, 185 liver transplants were performed in pediatric recipients of grafts from living donors. Among the donors, 166 left lateral segments (89.7%), 18 left lobes without the caudate lobe (9.7%) and 1 right lobe (0.5%) were harvested. The donor age ranged from 16 to 53 years, and the weight ranged from 47 to 106 kg. In 10 donors, an additional graft of the donor inferior mesenteric vein was harvested to substitute for a hypoplastic recipient portal vein. The transfusion of blood products was required in 15 donors (8.1%). The mean hospital stay was 5 days. No deaths occurred, but complications were identified in 23 patients (12.4%): 9 patients experienced abdominal pain and severe gastrointestinal symptoms and 3 patients required reoperations. Eight donors presented with minor bile leaks that were treated conservatively, and 3 patients developed extra-peritoneal infections (1 wound collection, 1 phlebitis and 1 pneumonia). Eight grafts (4.3%) showed primary dysfunction resulting in recipient death (3 cases of fulminant hepatitis, 1 patient with metabolic disease, 1 patient with Alagille syndrome and 3 cases of biliary atresia in infants under 1 year old). There was no relation between donor complications and primary graft dysfunction (P = 0.6).

Conclusions

Living donor transplantation is safe for the donor and presents a low morbidity. The donor surgery may be performed by a team of trained pediatric surgeons.     

Availability of ulipristal acetate: A secret shopper survey of pharmacies in a metropolitan area on emergency contraception

ObjectivesTo assess levonorgestrel (LNG) and ulipristal acetate (UPA) availability in pharmacies in a metropolitan area.MethodsA cross-sectional survey was conducted of all identified pharmacies within 25 miles of an urban medical center in Kansas City, KS. We categorized the pharmacies as dedicated commercial (national chains), store-associated (affiliated with a general merchandise or grocery store), or independent. We assessed LNG and UPA availability or time to availability if not currently stocked.ResultsWe contacted 165 pharmacies. Of the 165 pharmacies, few stocked UPA (12/165, 7%) whereas the majority stocked oral LNG (128/165, 78%). Dedicated commercial pharmacies were more likely to carry UPA than store-associated and independent pharmacies (11/84 [13%] vs. 1/61 [1%] vs. 0/20, respectively; P = 0.016). Most pharmacies that did not stock UPA reported that they could obtain it within 24 hours (94/153, 62%). Dedicated commercial pharmacies were most likely report the ability to obtain UPA in 24 hours (P = 0.016).ConclusionFew pharmacies stock UPA, the most effective form of oral emergency contraception. Enhanced communication between medical providers and pharmacists within current laws and regulations could enhance patient access to UPA.     

The Plasmodium falciparum eIK1 kinase (PfeIK1) is central for melatonin synchronization in the human malaria parasite. Melatotosil blocks melatonin action on parasite cell cycle

Melatonin and its indoles derivatives are central in the synchronization of malaria parasites. In this research, we discovered that melatonin is unable to increase the parasitemia in the human malaria Plasmodium falciparum that lacks the kinase PfeIK1. The PfeIK1 knockout strain is a valuable tool in the screening of indol-related compound that blocks the melatonin effect in wild-type (WT) parasite development. The assays were performed by using flow cytometry with simultaneous labeling for mitochondria viability with MitoTracker Deep Red and nucleus staining with SYBR Green. We found that Melatotosil leads to an increase in parasitemia in P. falciparum and blocks melatonin effect in the WT parasite. Using microscopy imaging system, we found that Melatotosil at 500 nM is able to induce cytosolic calcium rise in transgenic PfGCaMP3 parasites. On the contrary, the compound Triptiofen blocks P. falciparum cell cycle with IC₅₀ 9.76 µM ± 0.6, inhibits melatonin action, and does not lead to a cytosolic calcium rise in PfGCaMP3 parasites. We also found that the synthetic indol-related compounds arrested parasite cycle for PfeIK1 knockout and (WT) P. falciparum (3D7) in 72 hours culture assays with the IC₅₀ values slighting lower for the WT strain. We concluded that the kinase PfeIK1 is central for melatonin downstream signaling pathways involved in parasite cell cycle progression. More importantly, the indol-related compounds block its cycle as an upstream essential mechanism for parasite survival. Our data clearly show that this class of compounds emerge as an alternative for the problem of resistance with the classical antimalarials.