Synthesis, antibiofilm activity and molecular docking of N-acylhomoserine lactones containing cinammic moieties.

We prepared a series of cinnamoyl-containing furanones by an affordable and short synthesis. The nineteen compounds hold a variety of substituents including electron-donating, electron-withdrawing, bulky and meta-substituted phenyls, as well as heterocyclic rings. Compounds showed antibiofilm activity in S. aureus, K. pneumoniae and, more pronounced, against P. aeruginosa. The disruption of quorum sensing (QS) was tested using the violacein test and molecular docking predicted the antagonism of LasR as a plausible mechanism of action. The trimethoxylated and diene derivatives showed the best antibiofilm and anti-QS properties, thus becoming candidates for further modifications.

Technical note: An automated document verification tool in radiation oncology EMR: Application for LDR prostate brachytherapy.

PURPOSE: This study aims to illustrate how a script-based automated tool can efficiently verify documentation for LDR prostate brachytherapy. METHODS AND MATERIALS: An in-house Python-scripts-based tool was developed to automatically verify the specific checklists, aligned with our institutional practice guidelines for prostate seed implants (PSI). The scripts, compatible with our radiation oncology information system, could be executed with an optional web-based middleware to access and evaluate Aria documents. Optimized based on data from the previous 400 patients, the automated tool was applied to a random cohort of 50 LDR patients. It evaluated the adequacy of specific EMR documents by performing checks for data completeness, consistency, and allowable value range. We analyzed the efficiency of using this tool against conventional manual checks in two LDR processes: seed ordering and monthly audits for our PSI programs. RESULTS: The automated tool effectively performed chart checks on the involved PSI documents. Human errors, such as typos and inconsistent information, were identified in 7 out of 50 patients during the seed ordering process and in 2 out of 50 patients during the monthly audit. Meanwhile, this automation reduced the majority of manual chart-checking time by an average of 5 and 10 min per patient for these processes, respectively. The anticipated efficiency gains will continue to accrue as more check items are digitalized and assessable to the scripts. CONCLUSIONS: The implementation of an automated tool tailored for LDR prostate brachytherapy has demonstrated its efficiency benefits. Such an approach can help other clinics substantially enhance routine chart checks, periodic audits, and other applications in similar clinical settings.

Correlation of treatment time to target volume for GammaPod treatments: A simple second calculation.

PURPOSE: The GammaPod is a novel device for stereotactic breast treatments that employs 25 rotating Co-60 sources while the patient is continuously translated in three axes to deliver a highly conformal dose to the target. There is no commercial software available for independent second calculations. The purpose of this study is to determine an efficient way to estimate GammaPod treatment times based on target volume and use it as a second calculation for patient-specific quality assurance. METHODS: Fifty-nine GammaPod (Xcision Medical Systems, LLC.) breast cancer patient treatments were used as the fitting dataset for this study. Similar to the Curie-seconds concept in brachytherapy, we considered dose-rate × time/(prescribed dose) as a function of target volumes. Using a MATLAB (Mathworks, Natick, MA, USA) script, we generated linear (with 95% confidence interval (CI)) and quadratic fits and tested the resulting equations on an additional set of 30 patients. RESULTS: We found a strong correlation between the dose-rate × time/(prescribed dose) and patients' target volumes for both the linear and quadratic models. The linear fit was selected for use and using the polyval function in MATLAB, a 95% CI graph was created to depict the accuracy of the prediction for treatment times. Testing the model on 30 additional patients with target volumes ranging from 20 to 188 cc yielded treatment times from 10 to 25 min that in all cases were within the predicted CI. The average absolute difference between the predicted and actual treatment times was 1.0 min (range 0-3.3 min). The average percent difference was 5.8% (range 0%-18.4%). CONCLUSION: This work has resulted in a viable independent calculation for GammaPod treatment times. This method has been implemented as a spreadsheet that is ready for clinical use to predict and verify the accuracy of breast cancer treatment times.

Toward automation of initial chart check for photon/electron EBRT: the clinical implementation of new AAPM task group reports and automation techniques.

PURPOSE: The recently published AAPM TG-275 and the public review version of TG-315 list new recommendations for comprehensive and minimum physics initial chart checks, respectively. This article addresses the potential development and benefit of initial chart check automation when these recommendations are implemented for clinical photon/electron EBRT. METHODS: Eight board-certified physicists with 2-20 years of clinical experience performed initial chart checks using checklists from TG-275 and TG-315. Manual check times were estimated for three types of plans (IMRT/VMAT, 3D, and 2D) and for prostate, whole pelvis, lung, breast, head and neck, and brain cancers. An expert development team of three physicists re-evaluated the automation feasibility of TG-275 checklist based on their experience of developing and implementing the in-house and the commercial automation tools in our institution. Three levels of initial chart check automation were simulated: (1) Auto_UMMS_tool (which consists of in-house program and commercially available software); (2) Auto_TG275 (with full and partial automation as indicated in TG-275); and (3) Auto_UMMS_exp (with full and partial automation as determined by our experts' re-evaluation). RESULTS: With no automation of initial chart checks, the ranges of manual check times were 29-56 min (full TG-315 list) and 102-163 min (full TG-275 list), which varied significantly with physicists but varied little at different tumor sites. The 69 of 71 checks which were considered as "not fully automated" in TG-275 were re-evaluated with more automation feasibility. Compared to no automation, the higher levels of automation yielded a great reduction in both manual check times (by 44%-98%) and potentially residual detectable errors (by 15-85%). CONCLUSION: The initial chart check automation greatly improves the practicality and efficiency of implementing the new TG recommendations. Revisiting the TG reports with new technology/practice updates may help develop and utilize more automation clinically.

Dosimetric effects of the kV based image-guided radiation therapy of prone breast external beam radiation: Towards the optimized imaging frequency.

PURPOSE: For prone breast treatment, daily image-guided radiation therapy (IGRT) allows couch shifting to correct breast position relative to the treatment field. This work investigates the dosimetric effect of reducing kV imaging frequencies and the feasibility of optimizing the frequency using patient anatomy or their first 3-day shifts. METHOD: Thirty-seven prone breast patients who had been treated with skin marker alignment followed by daily kV were retrospectively analyzed. Three IGRT schemes (daily-kV, weekly-kV, no-kV) were simulated, assuming that fractions with kV imaging deliver a dose distribution equivalent to that in computed tomography (CT) planning, whereas other fractions yield a dose distribution as recreated by shifting the CT plan isocenter back to its position before the couch shift was applied. Treatment dose to targets (breast and lumpectomy cavity [LPC]) and organs at risks (OAR)s (heart, ipsilateral lung) in different schemes were calculated. Patient anatomy information on CT plans and first 3-day couch shift data were analyzed to investigate whether these factors could guide imaging scheme optimization. RESULTS: When kV imaging frequency was reduced, the percentage dose changes (δD) for breast and LPC objectives (average <1%) were smaller than those for heart and lung (average 28%-31% for Dmean ). In general, the δD of no-kV imaging was approximately that of weekly kV imaging × a factor of 1.2-1.4. Although most dose objectives were not affected, the potential higher heart dose may be of concern. No strong correlation was found between δD for different kV frequencies and patient anatomy size/distance or the first 3-day couch shift data. CONCLUSIONS: Despite resulting in lower imaging dose, time, cost, and similar target coverage, a reduction in kV imaging frequency may introduce higher heart complication risk. Daily kVs are needed more in left-sided breast patients. A less frequent imaging schedule, if considered, cannot be individually optimized using CT anatomic features or early shift data.

In response to bacteria, neutrophils release extracellular vesicles capable of initiating thrombin generation through DNA-dependent and independent pathways.

Neutrophils release extracellular vesicles (EVs) and some subsets of neutrophil-derived EVs are procoagulant. In response to S. aureus, neutrophils produce EVs that associate electrostatically with neutrophil extracellular traps (NETs). DNA in NETs is procoagulant, but whether neutrophil EVs produced during bacterial challenge have similar activity is unknown. Given that EV activity is agonist- and cell-type dependent and coagulation contributes to sepsis, we hypothesized that sepsis-causing bacteria increase production of neutrophil-derived EVs, as well as EV-associated DNA, and intact EVs and DNA cause coagulation. We recovered EVs from neutrophils challenged with S. aureus (SA), S. epidermidis (SE), E. coli (EC), and P. aeruginosa (PA), and measured associated DNA and procoagulant activity. EVs from SA-challenged neutrophils (SA-EVs), which were previously characterized, displayed dose-dependent procoagulant activity as measured by thrombin generation (TG) in platelet-poor plasma. EV lysis and DNase treatment reduced TG by 90% and 37%, respectively. SE, EC, and PA also increased EV production and EV-associated extracellular DNA, and these EVs were also procoagulant. Compared to spontaneously released EVs, which demonstrated some ability to amplify Factor XII-dependent coagulation in the presence of an activator, only EVs produced in response to bacteria could initiate the pathway. SA-EVs and SE-EVs had more surface-associated DNA than EC-EVs and PA-EVs, and SA-EVs and SE-EVs contributed to initiation and amplification of TG in a DNA-dependent manner. However, DNA on EC- or PA-EVs played no role, suggesting that neutrophils release procoagulant EVs which can activate the coagulation cascade through both DNA-dependent and independent mechanisms.

Racial Analysis of Clinical and Biochemical Outcomes in Patients With Prostate Cancer Treated With Low-Dose-Rate Brachytherapy.

PURPOSE: Black men in the United States experience significantly higher incidence of and mortality from prostate cancer (PCa) than non-Black men. The cause of this disparity is multifactorial, though inequitable access to curative radiation modalities, including low-dose-rate (LDR) brachytherapy, may contribute. Despite this, there are few analyses evaluating the potential of different radiation therapies to mitigate outcome disparities. Therefore, we examined the clinical outcomes of Black and non-Black patients treated with definitive LDR brachytherapy for PCa. METHODS: Data were collected for all patients treated with definitive LDR brachytherapy between 2005 and 2018 on a retrospective institutional review board approved protocol. Pearson χ2 analysis was used to assess demographic and cancer differences between Black and non-Black cohorts. Freedom from biochemical failure (FFBF) was calculated using Kaplan-Meier analysis. Univariate and multivariate analyses were used to identify factors predictive of biochemical failure. RESULTS: One hundred and sixty-seven patients were included in the analysis (Black: n = 81; 48.5%) with a median follow-up of 88.4 months. Black patients were from lower income communities (P < .01), had greater social vulnerability (P < .01), and had a longer interval between diagnosis and treatment (P = .011). Overall cumulative FFBF was 92.3% (95% confidence interval [CI], 87.8%-96.8%) at 5 years and 87.7% (95% CI, 82.0%-93.4%) at 7 years. There was no significant difference in FFBF in Black and non-Black patients (P = .114) and Black race was not independently predictive of failure (hazard ratio, 1.51; 95% CI, 0.56-4.01; P = .42). Overall survival was comparable between racial groups (P = .972). Only nadir prostate-specific antigen was significantly associated with biochemical failure on multivariate (hazard ratio, 3.57; 95% CI, 02.44-5.22; P < .001). CONCLUSIONS: Black men treated with LDR brachytherapy achieved similar FFBF to their non-Black counterparts despite poorer socioeconomic status. This suggests that PCa treatment with brachytherapy may eliminate some disparities in clinical outcomes.

Proton Arc Therapy vs Interstitial HDR Brachytherapy in Gynecologic Cancer with Parametrial/pelvic Side Wall Extension.

Purpose: To investigate whether volumetric-modulated proton arc therapy (VPAT) plans generate comparable doses to organs at risk (OARs) compared with interstitial high-dose-rate (iHDR) brachytherapy for patients with gynecologic cancer with disease extension to parametrial/pelvic side wall, who are not eligible for the aggressive procedure. Materials and Methods: VPAT delivers proton arc beams by modulated energies at the beam nozzle while maintaining the same incident energy to the gantry during the arc rotation. Plans of 10 patients previously treated with iHDR brachytherapy for high-risk clinical treatment volumes (HRCTV; 31.8-110.6 cm3; lateral dimensions, 4.2-5.6 cm) were selected and compared with VPAT plans. VPAT plans for each patient were designed using a 152- to 245-MeV range of energy-modulated proton beams. Results: HRCTV coverage of the VPAT plans was comparable to that of the iHDR plans, with V150% showing no statistical differences. On average, the V100% and V90% of VPAT plans were higher than those of the iHDR plans, 95.0% vs 91.9% (P = .02) and 98.6% vs 97.5% (P = .02), respectively. D100 was also 17% higher for the VPAT plans (P = .03). On average, the D2cm3 of bladder, rectum, and small bowels in the VPAT plans were considerably lower than those in iHDR plans (by 17.4%, 35.2%, and 65.6%, respectively; P < .05 for all OARs). Conclusion: VPAT-generated plans were dosimetrically superior to those with HDR brachytherapy with interstitial needles for locally advanced gynecologic cancer with parametrial/pelvic side wall disease extension. Dosimetrically, VPAT provides a noninvasive alternative to iHDR brachytherapy with a superior dosimetric profile.

Trypanosoma cruzi Antigenic Proteins Shared with Acute Lymphoblastic Leukemia and Neuroblastoma.

Background. Research studies indicate that immunization with protein extracts of Trypanosoma cruzi, the protozoan parasite that causes Chagas disease, prevents the appearance of tumors in 60% of mice injected with the murine lung carcinoma tumor line. The molecular basis of this process is unknown, although the presence of specific antigens in tumor cells and on the surface of T. cruzi suggests an antiparasitic immune response, with an effective cross-reaction against cancer cells, hence the importance to identify the antigens involved and determine their potential as target cells in anticancer therapy. Aim. This study aimed to determine the presence of antigenic proteins of T. cruzi shared with acute lymphoblastic leukemia and neuroblastoma cells. Material and methods. To achieve this, polyclonal antibodies against T. cruzi were developed in rabbits, and reactivity was determined with protein extracts of acute lymphoblastic leukemia cells and neuroblastoma. The immunodetection of five different strains of T. cruzi against anti-T. cruzi polyclonal antibodies was also performed. Conclusion. The study allows the knowledge of the immunological interactions between cancer and parasites to be expanded and, therefore, contributes to the design of more and better projects that improve the therapeutic strategies applied in oncology.

Deformable planning CT to cone-beam CT image registration in head-and-neck cancer.

PURPOSE: The purpose of this work was to implement and validate a deformable CT to cone-beam computed tomography (CBCT) image registration method in head-and-neck cancer to eventually facilitate automatic target delineation on CBCT. METHODS: Twelve head-and-neck cancer patients underwent a planning CT and weekly CBCT during the 5-7 week treatment period. The 12 planning CT images (moving images) of these patients were registered to their weekly CBCT images (fixed images) via the symmetric force Demons algorithm and using a multiresolution scheme. Histogram matching was used to compensate for the intensity difference between the two types of images. Using nine known anatomic points as registration targets, the accuracy of the registration was evaluated using the target registration error (TRE). In addition, region-of-interest (ROI) contours drawn on the planning CT were morphed to the CBCT images and the volume overlap index (VOI) between registered contours and manually delineated contours was evaluated. RESULTS: The mean TRE value of the nine target points was less than 3.0 mm, the slice thickness of the planning CT. Of the 369 target points evaluated for registration accuracy, the average TRE value was 2.6 +/- 0.6 mm. The mean TRE for bony tissue targets was 2.4 +/- 0.2 mm, while the mean TRE for soft tissue targets was 2.8 +/- 0.2 mm. The average VOI between the registered and manually delineated ROI contours was 76.2 +/- 4.6%, which is consistent with that reported in previous studies. CONCLUSIONS: The authors have implemented and validated a deformable image registration method to register planning CT images to weekly CBCT images in head-and-neck cancer cases. The accuracy of the TRE values suggests that they can be used as a promising tool for automatic target delineation on CBCT.

Aleatory Trypanosoma cruzi Vertical Transmission in Chiapas, Mexico: A Case Report.

Congenital Chagas disease is considered a form of dispersion of Trypanosoma cruzi related to human migration from endemic, often rural to previously non-endemic urban areas. This fact increases the Chagas disease establishment risk inside of family members by vertical transmission pathway. Congenital Chagas disease cases in newborns could not identified by the health professional even in endemic regions. Here we present the first family cluster of Chagas disease cases from Chiapas: one of the most important endemic areas in South of Mexico, where vertical T. cruzi transmission incidence rate is ranged between 2% to 22% revealing an important public health problem. Two cases inside a family from Chiapas, México with positive antibodies against T. cruzi detected by ELISA are presented; one of them got the infection through vertical pathway. We think that congenital Chagas disease should not be ignored in a newborn born from an asymptomatic Chagas disease mother, who may transmit the parasite infection randomly.

Mechanistic formulation of a lineal-quadratic-linear (LQL) model: split-dose experiments and exponentially decaying sources.

PURPOSE: In recent years, several models were proposed that modify the standard linear-quadratic (LQ) model to make the predicted survival curve linear at high doses. Most of these models are purely phenomenological and can only be applied in the particular case of acute doses per fraction. The authors consider a mechanistic formulation of a linear-quadratic-linear (LQL) model in the case of split-dose experiments and exponentially decaying sources. This model provides a comprehensive description of radiation response for arbitrary dose rate and fractionation with only one additional parameter. METHODS: The authors use a compartmental formulation of the LQL model from the literature. They analytically solve the model's differential equations for the case of a split-dose experiment and for an exponentially decaying source. They compare the solutions of the survival fraction with the standard LQ equations and with the lethal-potentially lethal (LPL) model. RESULTS: In the case of the split-dose experiment, the LQL model predicts a recovery ratio as a function of dose per fraction that deviates from the square law of the standard LQ. The survival fraction as a function of time between fractions follows a similar exponential law as the LQ but adds a multiplicative factor to the LQ parameter beta. The LQL solution for the split-dose experiment is very close to the LPL prediction. For the decaying source, the differences between the LQL and the LQ solutions are negligible when the half-life of the source is much larger than the characteristic repair time, which is the clinically relevant case. CONCLUSIONS: The compartmental formulation of the LQL model can be used for arbitrary dose rates and provides a comprehensive description of dose response. When the survival fraction for acute doses is linear for high dose, a deviation of the square law formula of the recovery ratio for split doses is also predicted.

Multicriteria optimization: Site-specific class solutions for VMAT plans.

Multicriteria optimization (MCO), a novel commercially available optimization method for IMRT and VMAT has the potential to improve treatment planning techniques and workflows. MCO allows planners and physicians to assess in real time the impact and tradeoffs between all clinical goals and organ constraints. We investigate the feasibility of a universal set of objectives and constraints for VMAT plans in different anatomical sites and the impact of involving the Physician in the navigation of the generated Pareto plans. We randomly selected 20 prostate only, 14 whole pelvis, 10 advanced lung, 15 pancreas, and 7 head and neck plans planned with a VMAT technique. Using the clinically delivered isocenter and beam set-up, we retrospectively generated MCO plans with a universal set of constraints and objectives for each anatomical site. The MCO plan scores were compared with clinical plans or an independent plan generated with DMPO. For prostate only plans the TCP values for the clinical and MCO plans were similar and the rectum NTCP values and overall P+ were slightly better for the MCO plans. For whole pelvis, the resulting MCO plans were comparable in all the dosimetric measures to the clinical plans. For lung, the MCO dosimetric comparison also yielded comparable plans but when evaluating individual patients, there were 5 patients for which MCO plans had a clear advantage in reducing dose to lung and/or esophagus while improving/maintaining target coverage, 4 patients with comparable plans and 1 patient where MCO was worse. Allowing the physician to navigate independently produced a different selection of dosimetric trade-offs. Comparable MCO plans were also obtained for pancreas and head and neck. Based on our experience with many anatomical sites and a large number of patient plans, we have found that VMAT MCO plans are comparable to the clinical plans and can be produced with a universal set of objectives and constraints, even for a wide range of geometries and anatomies.

Co-infection of Dengue, Zika and Chikungunya in a group of pregnant women from Tuxtla Gutiérrez, Chiapas: Preliminary data. 2019.

INTRODUCTION: Dengue, Zika and Chikungunya are RNA Arboviruses present in some areas of Mexico, mainly in the endemic state of Chiapas that is characterized by presence of the vector that transmit them and an ecology that favors high transmission. According to the national epidemiological surveillance system, Dengue has intensified since 2018 and outbreaks continue in various states while for Zika and Chikungunya a decrease in cases has been reported in recent years. The main objective of this study was to determine the incidence of Dengue, Zika and Chikungunya infections during pregnancy in the state of Chiapas. PRINCIPAL FINDINGS: The presence of previous and current infections and coinfections diagnosed by molecular (RT-PCR) and immunological (ELISA for IgG determination) techniques indicates a wide circulation of viruses in asymptomatic people, specifically in pregnant women showing that silent infections in dry season contributes to the preservation of viruses. CONCLUSIONS: From 136 studied samples, 27.7% tested positive for DENV, 8% for ZIKV and 24.1% for CHIKV by RTPCR and the values of IgG in sera show that 83.9% were positive for IgG antibodies against DENV, 65% against ZIKV and 59.1% against CHIKV. Results demonstrated presence of ZIKV and CHIKV, not detected by the epidemiological surveillance system, so the importance of establishing proactive epidemiological systems more strict, especially because these infections in pregnant women can cause severe health problems for newborn children.

Correlation of radiation dose and activity with clinical outcomes in metastatic colorectal cancer after selective internal radiation therapy using yttrium-90 resin microspheres.

PURPOSE: Yttrium-90 (Y)-resin microspheres are prescribed using activity. We evaluated overall survival (OS) and radiographic tumor response after selective internal radiation therapy (SIRT) with resin microspheres in patients with liver metastases from colorectal cancer. PATIENTS AND METHODS: We retrospectively reviewed 60 metastatic colorectal cancer patients treated at our institution with SIRT using Y-resin microspheres. Each patient underwent pre-SIRT MRI or computed tomography imaging of the liver with intravenous contrast. Patients underwent post-treatment imaging at 2-3-month intervals with response assessed according to unidimensional Response Evaluation Criteria in Solid Tumors (RECIST) criteria as well as published three-dimensional volumetric criteria. We then related the prescribed activity established by the body surface area method and the corresponding prescribed dose to radiographic treatment response and OS. RESULTS: The median follow-up after the first SIRT treatment was 8.9 months. The mean prescribed activity and the prescribed dose were 26.6 mCi and 52.8 Gy, respectively. OS was not significantly associated with either prescribed activity or prescribed dose. Prescribed dose was also not related to response. However, a significant relationship was found between a higher prescribed activity and an improved radiographic response by RECIST (P=0.04) at the second follow-up. CONCLUSION: The prescribed activity of Y-resin microspheres may be correlated with radiographic response by RECIST criteria at 4-6 months post-treatment. For a more accurate prediction of response, a valid dose calculation model based on post-Y PET dosimetry is likely needed given the heterogeneous dose delivery seen in SIRT.

EAST Multicenter Trial on targeted temperature management for hanging-induced cardiac arrest.

BACKGROUND: We sought to determine the outcome of suicidal hanging and the impact of targeted temperature management (TTM) on hanging-induced cardiac arrest (CA) through an Eastern Association for the Surgery of Trauma (EAST) multicenter retrospective study. METHODS: We analyzed hanging patient data and TTM variables from January 1992 to December 2015. Cerebral performance category score of 1 or 2 was considered good neurologic outcome, while cerebral performance category score of 3 or 4 was considered poor outcome. Classification and Regression Trees recursive partitioning was used to develop multivariate predictive models for survival and neurologic outcome. RESULTS: A total of 692 hanging patients from 17 centers were analyzed for this study. Their overall survival rate was 77%, and the CA survival rate was 28.6%. The CA patients had significantly higher severity of illness and worse outcome than the non-CA patients. Of the 175 CA patients who survived to hospital admission, 81 patients (46.3%) received post-CA TTM. The unadjusted survival of TTM CA patients (24.7% vs 39.4%, p < 0.05) and good neurologic outcome (19.8% vs 37.2%, p < 0.05) were worse than non-TTM CA patients. However, when subgroup analyses were performed between those with an admission Glasgow Coma Scale score of 3 to 8, the differences between TTM and non-TTM CA survival (23.8% vs 30.0%, p = 0.37) and good neurologic outcome (18.8% vs 28.7%, p = 0.14) were not significant. Targeted temperature management implementation and post-CA management varied between the participating centers. Classification and Regression Trees models identified variables predictive of favorable and poor outcome for hanging and TTM patients with excellent accuracy. CONCLUSION: Cardiac arrest hanging patients had worse outcome than non-CA patients. Targeted temperature management CA patients had worse unadjusted survival and neurologic outcome than non-TTM patients. These findings may be explained by their higher severity of illness, variable TTM implementation, and differences in post-CA management. Future prospective studies are necessary to ascertain the effect of TTM on hanging outcome and to validate our Classification and Regression Trees models. LEVEL OF EVIDENCE: Therapeutic study, level IV; prognostic study, level III.

A radiobiological model of reoxygenation and fractionation effects.

PURPOSE: The purpose of this study was to develop a radiobiological model of reoxygenation that fulfills the following goals: (a) Quantify the reoxygenation effect for different fractionations (b) Model the hypoxic fraction in tumors as a function of the number of radiation treatments. (c) Develop a simple analytical expression for a reoxygenation term in biological effect calculations. METHOD: The model considers tumor cells in two compartments: an aerobic (or normoxic) population of cells and a hypoxic population including cells under a range of reduced oxygen concentrations. The surviving fraction is predicted using the linear-quadratic (LQ) model. A hypoxia reduction factor (HRF) is used to quantify reductions in radiosensitivity parameters αA and ßA as cellular oxygen concentration decreases. The HRF is defined as the ratio of the dose at a specific level of hypoxia to the dose under fully aerobic conditions to achieve equal cell killing. The model assumes that a fraction of the hypoxic cells (Δ) moves from the hypoxic to the aerobic compartment after each daily fraction. As an example, we compare the effect of reoxygenation on biological response for a standard dose fractionation for nonsmall cell lung cancer (NSCLC) (d = 2 Gy, n = 33) to typical fractionations for stereotactic body radiotherapy (SBRT) and other nonstandard fractionations. RESULTS: The reoxygenation effect is parameterized for biological effect calculations and an analytic expression for the surviving fraction after n daily treatments is derived. The hypoxic fraction either increases or decreases with n depending on the reoxygenation parameter Δ. For certain combinations of parameters, the biological effect of reoxygenation goes as -(n-1) · ln(1-Δ) providing a simple expression that can be introduced in biologically effective dose (BED) calculations. The model is used to compare fractionation schedules and quantitatively interpret results from molecular imaging studies of hypoxia. Based on the comparison of conventional fractionation and hypo- and hyper-fractionation for NSCLC, the value of Δ is estimated to be between 0.1 and 0.2 assuming plausible radiobiological parameters from the literature. This value is consistent with the preliminary analysis of the molecular imaging studies. CONCLUSIONS: A novel radiobiological model was developed that can be used to evaluate the effect of reoxygenation in fractionated radiotherapy.

Halftime for repair of sublethal damage in normal bladder and rectum: an analysis of clinical data from cervix brachytherapy.

The halftime for repair of sub-lethal damage is an important radiobiological parameter in analysing radiation responses and in designing new treatments involving different dose rates. This work is to resolve an inconsistency existing in the repair halftime for the bladder and rectum, two of the most dose limiting critical structures for pelvic irradiation. Both long (1.5-2 h) and short (0.3-1 h) repair halftimes have been reported previously. In this work, by reconciling clinical data from cervical brachytherapy of different dose rates and by introducing a sparing factor to consider the dose sparing occurring for critical structures, we have estimated that the most likely value of the repair halftime for bladder and rectum is short, 0.2-0.4 h if assuming alpha/beta = 2-4 Gy. The present analysis does not support the long repair halftimes reported previously for the bladder and rectum and for other normal structures.

Clinical implementation of an electron monitor unit dosimetry system based on task group 71 report and a commercial calculation program.

Many clinics still use monitor unit (MU) calculations for electron treatment planning and/or quality assurance (QA). This work (1) investigates the clinical implementation of a dosimetry system including a modified American Association of Physicists in Medicine-task group-71 (TG-71)-based electron MU calculation protocol (modified TG-71 electron [mTG-71E] and an independent commercial calculation program and (2) provides the practice recommendations for clinical usage. Following the recently published TG-71 guidance, an organized mTG-71E databook was developed to facilitate data access and subsequent MU computation according to our clinical need. A recently released commercial secondary calculation program - Mobius3D (version 1.5.1) Electron Quick Calc (EQC) (Mobius Medical System, LP, Houston, TX, USA), with inherent pencil beam algorithm and independent beam data, was used to corroborate the calculation results. For various setups, the calculation consistency and accuracy of mTG-71E and EQC were validated by their cross-comparison and the ion chamber measurements in a solid water phantom. Our results show good agreement between mTG-71E and EQC calculations, with average 2% difference. Both mTG-71E and EQC calculations match with measurements within 3%. In general, these differences increase with decreased cutout size, increased extended source to surface distance, and lower energy. It is feasible to use TG71 and Mobius3D clinically as primary and secondary electron MU calculations or vice versa. We recommend a practice that only requires patient-specific measurements in rare cases when mTG-71E and EQC calculations differ by 5% or more.