Feasibility of IMRT to Cover Pelvic Nodes While Escalating the Dose to the Prostate Gland: Dosimetric Data on 35 Consecutive Patients

Utilizing available dosimetric and acute toxicity data, we confirm the feasibility of intensity modulated radiotherapy (IMRT) to include treatment of the pelvic nodes (PN) while escalating the dose to the prostate. Data were obtained from 35 consecutive patients with prostate cancer with ≥15% risk of PN involvement. Patients received an initial boost to the prostate, delivering 16 Gy over 8 fractions using a 6-field conformal technique, followed by an 8-field coplanar inverse planning IMRT technique delivering an additional 60 Gy over 30 fractions to the prostate (76 Gy total) and 54 Gy over 30 fractions to the seminal vesicles (SV) and PN. Dose-volume histogram analysis was performed for planning target volumes and organs at risk. Acute toxicity (RTOG/EORTC scale) was prospectively and independently scored weekly for each patient. The maximum, mean, minimum dose, and D95 to each planning target volume is provided: prostate (82.2, 78.2, 72.6, 75.2 Gy), SV (79.0, 72.5, 56.9, 61.1 Gy), and PN (80.4, 59.7, 46.5, 53.3 Gy), respectively. The percent volume receiving a dose at or above “x” Gy (Vx) was recorded for V75, V70, V65, V60, and V50 as: bladder (14%, 24%, 32%, 39%, and 54%) and rectum (3%, 18%, 26%, 34%, and 51%), respectively. Acute toxicity was as follows: 54% grade 2+ GI (n = 19), 25% grade 2+ GU (n = 9). IMRT enables treatment of pelvic nodes while escalating dose to the prostate and is clinically feasible with acute toxicity within expected ranges.     

IMRT to Escalate the Dose to the Prostate while Treating the Pelvic Nodes

Background and Purpose:  

To assess and quantify the benefit of introducing intensity–modulated radiotherapy (IMRT) over conventional approaches to cover the pelvic nodes while escalating the dose to the prostate gland.     

Surveillance of patients with Barrett's esophagus for dysplasia and cancer with balloon cytology

BACKGROUND & AIMS: A less costly cancer surveillance method for Barrett's esophagus is desirable. The aim of this study was to compare nonendoscopic balloon cytology with biopsy and brush cytology for detecting dysplasia and carcinoma in patients with Barrett's esophagus. METHODS: Patients in a surveillance program underwent balloon cytology before endoscopy with biopsy and brush cytology. Results of cytology were compared with those of histology. RESULTS: Adequate columnar epithelium was obtained in 52 of 63 (83%) patients with balloon cytology and 59 of 61 (97%) with brush cytology. Balloon cytology obtained abnormal cells in 6 of 8 patients with adenocarcinoma, 2 of 2 patients with high-grade dysplasia, and 2 of 8 patients with low-grade dysplasia. Sensitivity of balloon cytology for high-grade dysplasia or carcinoma was 80% but only 25% for low-grade dysplasia. No patients without dysplasia or carcinoma had abnormal cells. Brush cytology was abnormal in all 11 patients with high-grade dysplasia or carcinoma but only 2 of 9 patients with low-grade dysplasia (sensitivity, 22%). Two of 39 patients without dysplasia had abnormal cells (specificity, 95%). Balloon cytology cost was sixfold less than endoscopy with biopsy. CONCLUSIONS: Balloon cytology detected 80% of patients with high-grade dysplasia or carcinoma when sampling was adequate. Brush cytology data suggest that a more abrasive balloon may improve balloon cytology sensitivity. The potential cost savings of balloon cytology compared with endoscopic cancer surveillance in Barrett's esophagus support further studies of this technique. (Gastroenterology 1997 Jun;112(6):1787-97)     

Failure of collateral blood flow is associated with infarct growth in ischemic stroke

Changes in collateral blood flow, which sustains brain viability distal to arterial occlusion, may impact infarct evolution but have not previously been demonstrated in humans. We correlated leptomeningeal collateral flow, assessed using novel perfusion magnetic resonance imaging (MRI) processing at baseline and 3 to 5 days, with simultaneous assessment of perfusion parameters. Perfusion raw data were averaged across three consecutive slices to increase leptomeningeal collateral vessel continuity after subtraction of baseline signal analogous to digital subtraction angiography. Changes in collateral quality, Tmax hypoperfusion severity, and infarct growth were assessed between baseline and days 3 to 5 perfusion–diffusion MRI. Acute MRI was analysed for 88 patients imaged 3 to 6 hours after ischemic stroke onset. Better collateral flow at baseline was associated with larger perfusion–diffusion mismatch (Spearman''s Rho 0.51, P<0.001) and smaller baseline diffusion lesion volume (Rho −0.70, P<0.001). In 30 patients without reperfusion at day 3 to 5, deterioration in collateral quality between baseline and subacute imaging was strongly associated with absolute (P=0.02) and relative (P<0.001) infarct growth. The deterioration in collateral grade correlated with increased mean Tmax hypoperfusion severity (Rho −0.68, P<0.001). Deterioration in Tmax hypoperfusion severity was also significantly associated with absolute (P=0.003) and relative (P=0.002) infarct growth. Collateral flow is dynamic and failure is associated with infarct growth.     

Photochemical inactivation of pathogenic bacteria in human platelet concentrates

Platelet concentrates (PC) may be infrequently contaminated with low levels of bacteria that can cause septicemia and death in patients receiving transfusion therapy. We evaluated the efficacy of a photochemical decontamination (PCD) technique using 8-methoxypsoralen (8-MOP) and long wavelength UV light (UVA) to inactivate bacteria in standard therapeutic PC. Twelve phylogenetically distinct pathogenic bacteria, 5 gram-positive and 7 gram-negative organisms, were seeded into PC to a final challenge dose ranging from 10(5) to 10(7) colony- forming units (CFU)/mL. Contaminated PC were treated with 8-MOP (5 micrograms/mL) and 5 J/cm2 of UVA, a PCD treatment regimen found to adequately preserve in vitro platelet function. Greater than 10(5) CFU/mL of all 5 gram-positive (Staphylococcus aureus, Streptococcus epidermidis, Streptococcus pyogenes, Listeria monocytogenes, and Corynebacterium minutissimum) and 2 of the gram-negative (Escherichia coli and Yersinia enterocolitica) organisms were inactivated. The remaining 5 gram-negative organisms were more resistant, with less than 10(1) to 10(3.7) CFU/mL inactivated under these conditions. The inactivation efficiency for this resistant group of gram-negative organisms was improved when PC were resuspended in a synthetic storage medium with reduced plasma protein concentration (15%) and an increased 8-MOP concentration (23.4 micrograms/mL). Illumination with 3 J/cm2 of UVA in this system inactivated greater than 10(5) CFU/mL of 4 resistant gram-negative organisms (Salmonella choleraesuis, Enterobacter cloacae, Serratia marcescens, and Klebsiella pneumoniae) and 10(4.1) CFU/mL of the most resistant gram-negative organism (Pseudomonas aeruginosa). This level of PCD treatment did not adversely affect in vitro platelet function. These results demonstrate that PCD using 8-MOP (5 to 23.4 micrograms/mL) effectively inactivated high levels of pathogenic bacteria in PC with adequate preservation of in vitro platelet properties.     

Antimicrobial activity of different tissues of snakehead fish Channa striatus (Bloch)

ObjectiveThe aim of this study was to identify the presence of antimicrobial activity in different organs/tissues (gills, blood, skin, liver, intestine, kidney, tissue and ovary) extract of snakehead fish Channa striatus.MethodsA total of 48 fractions from the organs and tissue extracts were obtained by solid-phase extraction and the fractions were assayed for antimicrobial activity. The screening of antimicrobial activity for all the fractions were tested against 8 human pathogens including Gram positive (Methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus aureus, Bacillus cereus) and Gram negative bacteria (Salmonella enteritidis, Shigella flexneri, Acinetobacter baumanni, Escherichia coli, Klebsiella pneumoniae) using the British Society for Antimicrobial Chemotherapy (BSAC) standardized disc susceptibility test method. The activity was measured in terms of zone of inhibition in mm.ResultsThe results indicated that, among the 8 organs/tissues tested only blood and gills extract fractions (40 and 60 % ACN fraction) showed inhibition against Escherichia coli and 60 % ACN fraction of gill extract showed inhibition against Salmonella enteritidis. Protein profile analysis by SDS-PAGE showed that antimicrobial activity of the partially purified blood and gill tissue extracts might be due to low molecular weight peptides.ConclusionsThe present study showed that, gill and blood extracts of Channa striatus can be a potential source of an antimicrobial protein for specific human pathogens.     

Dosimetric comparison of conventional and forward-planned intensity-modulated techniques for comprehensive locoregional irradiation of post-mastectomy left breast cancers.

Three recently published randomized trials have shown a survival benefit to postoperative radiation therapy when the internal mammary chain (IMC), supraclavicular (SCV), and axillary lymphatics are treated. When treating the IMC, techniques that minimize dose to the heart and lungs may be utilized to prevent excess morbidity and mortality and achieve the survival benefit reported. The purpose of this study was to dosimetrically compare forward-planned intensity-modulated radiation therapy (fIMRT) with conventional techniques for comprehensive irradiation of the chest wall and regional lymphatics. For irradiation of the chest wall and IMC, 3 treatment plans, (1) fIMRT, (2) partially-wide tangent (PWT) fields, and (3) a photon-electron (PE) technique, were compared for 12 patients previously treated at our institution with fIMRT to the left chest wall and regional lymphatics. Additionally, the SCV and infraclavicular lymphatics were irradiated and 4 methods were compared: 2 with anterior fields only (dose prescribed to 3 and 5 cm [SC3cm, SC5cm]) and 2 with anterior and posterior fields (fIMRT, 3DCRT). Each patient was planned to receive 50 Gy in 25 fractions. Regions of interest (ROIs) created for each patient included chest wall (CW) planning target volume (PTV), IMC PTV, and SCV PTV. Additionally, the following organs at risk (OAR) volumes were created: contralateral breast, heart, and lungs. For each plan and ROI, target volume coverage (V(95-107)) and dose homogeneity (D(95-5)) were evaluated. Additionally, the mean OAR dose and normal tissue complication probability (NTCP) were computed. For irradiation of the CW, target volume coverage and dose homogeneity were improved for the fIMRT technique as compared to PE (p < 0.001, p = 0.023, respectively). Similar improvements were seen with respect to IMC PTV (p = 0.012, p = 0.064). These dosimetric parameters were also improved as compared to PWT, but not to the same extent (p = 0.011, p = 0.095 for CW PTV, and p = 0.164, p > 0.2 for IMC PTV). The PE technique resulted in the lowest heart V30, although this difference was not significant (p > 0.2). The NTCP values for excess cardiac mortality for fIMRT and PE were equivalent (1.9%) and lower than with PWT (2.8%, p > 0.2). The fIMRT technique was able to reduce heart dose and NTCP for each patient as compared to PWT. When comparing the anterior field techniques of treating SCV PTV, prescribing dose to 5 cm resulted in a improved V50 (p = 0.089). However, when compared to fIMRT, the SC3cm and SC5cm had inferior target volume coverage (p = 0.055, p = 0.014) and significantly greater dose heterogeneity (p = 0.031, p = 0.043). The addition of a posterior field increased the volume of lung receiving 40 and 50 Gy, but not significantly (p > 0.2). For complex breast treatments that irradiate the chest wall, IMC, and SCV, fIMRT resulted in improved dose homogeneity and target volume coverage as compared to conventional techniques. Furthermore, the dosimetric gains in target volume coverage with fIMRT came at no significant increase in dose to OAR. The fIMRT technique demonstrated the ability to maintain the advantage of each of the other 2 techniques: reducing the dose to OARs, as with PE, and providing superior target volume coverage, as with PWT.     

Image-based biomarkers in clinical practice

The growth of functional and metabolically informative imaging is eclipsing anatomic imaging alone in clinical practice. The recognition that magnetic resonance (MR) and positron emission tomography (PET)-based treatment planning and response assessment are essential components of clinical practice and furthermore offer the potential of quantitative analysis being important. Extracting the greatest benefit from these imaging techniques will require refining the best combinations of multimodality imaging through well-designed clinical trials that use robust image-analysis tools and require substantial computer based infrastructure. Through these changes and enhancements, image-based biomarkers will enhance clinical decision making and accelerate the progress that is made through clinical trial research.