Prediction Factors of Radiation Esophagitis in Breast Cancer Patients Undergoing Supraclavicular Radiotherapy.

Purpose: The aim of this study was to investigate demographic and dosimetric parameters which may link with esophagitis in patients with breast cancer receiving three-dimensional conformal radiotherapy to the supraclavicular fossa. Materials and Methods: We examined 27 breast cancer patients with supraclavicular metastases. All patients were treated with radiotherapy (RT) with a prescribed dose of 40.5 Gy in 15 fractions for 3 weeks. Esophagitis was recorded weekly and esophagus toxicity was evaluated and graded according to the tadiation therapy oncology group. The following factors were examined regarding their correlation with grade 1 or worse esophagitis by univariate and multivariate analyses: age, chemotherapy, smoking history, maximum dose (Dmax), mean dose (Dmean), esophagus volume receiving 10 Gy (V10), esophagus volume receiving 20 Gy (V20), and length of esophagus in the treatment field. Results: Of 27, 11 (40.7%) patients developed no esophageal irritation throughout therapy. Approximately half of the patients 13/27 (48.1%) had maximum grade 1 esophagitis. 2/27 (7.4%) patients had grade 2 esophagitis. The incidence of grade 3 esophagitis was (3.7%). Dmean, Dmax, V10, and V20 were 10.48 ± 5.10 Gy, 38.18 ± 5.12Gy, 29.83 ± 15.16, and 19.32 ± 10.01, respectively. Our results showed that Dmean, V10, and V20 were the significant factors for the development of esophagitis, whereas esophagitis was not significantly associated with the chemotherapy regimen, age, and smoking status. Conclusions: We found that Dmean, V10, and V20 correlated significantly with acute esophagitis. However, the chemotherapy regimen, age, and smoking status did not affect esophagitis development.

Development of a liquid chromatography-tandem mass spectrometry method for the analysis of docetaxel-loaded Poly(lactic-co-glycolic acid) nanoparticles.

Docetaxel is among the most effective chemotherapeutic agents used for the treatment of solid tumors, such as breast cancer. Targeting docetaxel to the tumor site would increase the safety and efficacy of the treatment. The focus of this work was to develop an efficient liquid chromatography tandem mass spectrometry (LC-MS/MS) method to quantify docetaxel entrapped in optimized poly lactic-co-glycolic acid (PLGA) nanoparticles. Several nanoparticle formulations were prepared to optimize the nanoparticles based on their size and yield percentage using a modified solvent evaporation technique. The MS/MS fingerprints of docetaxel and paclitaxel (as internal standard) were used to identify diagnostic product ion for developing a multiple reaction monitoring (MRM) LC-MS/MS method for the quantification of docetaxel in the PLGA nanoparticles. A triple quadrupole linear ion trap instrument (AB Sciex 4000 QTRAP) equipped with electrospray ionization was used. The optimized nanoparticles had a zeta potential of -23.2 ± 1.4 mV and mean particle sizes of 202.2 ± 4.7 nm and 251.7 ± 8.2 nm before and after freeze-drying, respectively. Polydispersity index values of the nanoparticles confirmed their uniform size distribution. The developed LC-MS/MS method could quantify docetaxel in the PLGA matrix with accuracy and precision covering a broad linear range of 15.6-4000 ng/mL. Method validation was conducted using the regulatory guidelines of the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) and showed acceptable values for all the tested criteria. The developed LC-MS/MS method with the novelty of using a phenyl column will be beneficial for future analysis of docetaxel loaded polymeric nano-delivery systems.

Comparison of esophagus dose in breast cancer patients undergoing supraclavicular irradiation with and without esophagus countering.

CONTEXT: Esophagus toxicity and the risk of esophageal cancer are linked to radiation dose to the esophagus in breast cancer patients undergoing supraclavicular irradiation. AIMS: The aim of this study was to evaluate the impact of esophagus contouring on the dose received in the esophagus in breast cancer patients undergoing supraclavicular irradiation. SETTING AND DESIGN: This study included 30 treatment plans for breast cancer patients who received 50 Gy/25 fractions (2 Gy/fraction/day) using 3D-conformal radiation therapy (3D-CRT) to the whole breast or chest wall and supraclavicular. METHODS AND MATERIALS: Our study included two groups: the non-sparing group was the treatment plan in which the esophagus was not delineated and the esophagus sparing group was generated, in which the plans were modified to spare the esophagus. The maximum dose, mean dose, and percentage of esophagus volume received, 5, 10, 15, and 20 Gy, respectively (V5, V10, V15, and V20), were used to evaluate both groups. STATISTICAL ANALYSIS: One-way analysis of variance was used. A P value <0.05 was considered statistically significant. RESULTS: The esophagus sparing group plans show a reduction in the esophageal mean dose Dmean (5.72 ± 5.15) Gy when compared to the non-sparing group (7.83 ± 3.31) Gy. Likewise, the maximum dose, V5, V10, V15, and V20 were reduced in the esophagus sparing group. All dosimetric parameters were significantly higher (P < 0.05) in patients with left breast cancer for both groups. CONCLUSION: Our results suggest that it is possible to reduce the dose to the esophagus by considering the esophagus during treatment planning while maintaining plan quality. This reduction could lead to the greatest predicted decrease in acute esophagitis and esophageal cancer.

Investigating the Sensitivity of New Formulation MAGAT and NIPAM Polymer Gels in the Radiation Therapy Dosimetry.

Background: Normoxic polymer gels have been used as a three dimensional (3D) dosimeter in radiation therapy, recently. The sensitivity of these gels is important in dosimetry and their improvement can be also useful. Objective: In this study, different modalities of gel reading were used and the structure of gel changed due to the best improvement of sensitivity. The sensitivities of the new formulation of Methacrylic acid gel (MAGAT) and N-isopropyl acrylamide (NIPAM) polymer gel dosimeters were studied using two different reading methods of magnetic resonance imaging (MRI) and X-ray computed tomography (X-ray CT). Material and Methods: In this experimental study, in addition to making the NIPAM polymer gel dosimeter, a new formulation of normoxic polymer gel dosimeter, which named MAGAT gel, was investigated. The gels were irradiated with 6 MV in low doses, including1, 1.5, 1.75, 2 and 2.5 Gy. MRI and X-ray CT did the reading of gel dosimeters a day after irradiation using an elevated protocol. Results: The dose sensitivities of 0.92 HGy-1 and 0.47 HGy-1 were obtained for new MAGAT and NIPAM polymer gel dosimeters, respectively, based on the X-ray CT reading modality. The use of MRI reading modality and the dose sensitivities were 0.74 S-1Gy-1 and 0.27 S-1Gy-1 for new MAGAT and NIPAM polymer gel dosimeters, respectively. Conclusion: The new formulation of MAGAT polymer gel with a suitable protocol of gel reading has a better response.

Evaluation of lung heterogeneity effects on dosimetric parameters in small photon fields using MAGIC polymer gel, Gafchromic film, and Monte Carlo simulation.

In this work, the performance of MAGIC polymer gel in measuring dosimetric parameters beyond lung heterogeneity in small fields was investigated. All data were obtained using MAGIC, EBT2, and MC in four small field sizes. The maximum local differences between MAGIC and MC were less than 5.1, 3.9, 3.1, and 2.6% for PDD values behind lung heterogeneity at 5, 10, 20, and 30 mm field sizes, respectively. The findings showed that MAGIC is a suitable tool for dosimetry behind low-density heterogeneity.

Improvement of sensitivity of X-ray CT reading method for polymer gel in radiation therapy.

BACKGROUND: Three dimensional (3D) dosimetry methods are useful for advanced radiotherapy techniques such as stereotactic radiosurgery (SRS) and high dose rate (HDR) brachytherapy. Polymer gel is one of the more reliable 3D dosimetry techniques. More studies are needed to improve the efficiency of polymer gels for their application in dosimetry. AIM: In the current study, the best protocol for reading of N-isopropyl acrylamide (NIPAM) polymer gel by X-ray computed tomography (CT) was implemented for application in radiotherapy. MATERIAL AND METHODS: The NIPAM gel was made and irradiated by 6 MV. Its reading was done by the X-ray CT after 24 h and the information examined by using the MATLAB software. In the present work, the different effects of slice thicknesses and voltages were investigated for its lower toxicity of NIPAM polymer gel. The results of a recipe of different filtering on the response curve of polymer gel was investigated. RESULTS: The measured dose sensitivity was Δ N C T H  = 0.29 ± 0.01 H G y - 1 for the NIPAM dosimeter. The best sensitivity was achieved for 120 kVp and the slice thickness of 10 mm. The greater slice thickness gained more desirable sensitivity. This process was repeated by using different filtering with different thicknesses to obtain the best sensitivity. CONCLUSIONS: The sensitivity of X-ray CT reading technique of NIPAM Polymer gel depended on the slice thickness and kVp. The wiener2 filtering was useful to improving sensitivity.

Potentiating Antigen Specific Immune Response by Targeted Delivery of the PLGA-Based Model Cancer Vaccine.

Targeted delivery of vaccine has the potential to localize the therapeutic agent to a target tissue with minimum side-effects. This article presents the development of a model targeted immunotherapeutic approach that will harness effective T cell response. Here, we investigated the impact of a model nanoparticulate cancer vaccine on the immune system of in vivo mice models. The nanoparticles (NPs) were prepared by a double emulsification solvent evaporation technique. The anti-CD205 targeted formulations were obtained either through physical adsorption or a covalent conjugation method. The structural integrity of ovalbumin (OV) was confirmed by circular dichroism spectroscopy. Flow cytometry and enzyme-linked immunosorbent assay experiments were performed to evaluate T cell proliferation and cytokine secretion. Our results indicate that the antigen-adjuvant combined formulation induced more powerful responses compared to formulations with either of these alone. Wild-type balb/c mice immunized with the targeted poly (D,L-lactic- co-glycolic-acid) (PLGA) NPs encapsulated with OV and monophosphoryl lipid A (MP) induced profound secretion of antigen-specific IgG antibodies and cytokines and generation of memory T cells. OV specific T cell receptor transgenic OT1 mice showed the highest production of cytotoxic T cells and increased the secretion of cytokines upon immunization with the targeted OVMP formulations. The enhanced response might be attributed to the OV depot effect at the subcutaneous site of injection that triggered effective induction of dendritic cells activation and helper T cell differentiation in the lymph nodes. Therefore, the developed targeted PLGA-based delivery system could be utilized as a successful model vaccine in the future.

The peripheral dose outside the applicator in electron beams of an Elekta linear accelerator.

Peripheral doses out of field could have short and long terms biological effects on patients treated with electron beams. In this study, peripheral dose outside the applicator was measured using the 6, 10 and 18 MeV beams of an Elekta synergy linac. For these beams dose profiles were measured using EBT3 film at various depths within a solid water phantom. Measurements were performed using 6 × 6, 10 × 10, 14 × 14 and 20 × 20 cm2 applicators at gantryangles of 0°, 10° and 20° and depths of 0, 0.5, 1 cm and depth of Dmax (maximum dose) for each energy. The peripheral dose profiles were normalized to the distance of 2 cm from the edge of each field. The largest peak of the peripheral dose was observed for 18 MeV 3 cm from the outer edge of the applicator. Peak dose increased with increasing energy. Peak dose at 18 MeV electron beam was 1.6% at the surface of phantom and at the distance of 2 cm from the outer edge of the applicator when the applicator of 20 × 20 cm2 was used. Peak dose at 6 MeV electron beam was 1.15% at the same distance in the same applicator size. It was found that the peak dose decreased with increasing depth and increased with increase in field size. Also, the peak dose moved towards CAX with increase in gantry angle.In general dose to tissue out of field could be reduced using appropriate shielding for each applicator and beam energy.

Energy and field size dependence of a silicon diode designed for small-field dosimetry.

PURPOSE: To investigate the energy dependence/spectral sensitivity of silicon diodes designed for small-field dosimetry and obtain response factors (RFs) for arbitrary photon spectra using Monte Carlo (MC) simulations. METHODS: The EGSnrc user-code DOSRZnrc was used to calculate the dose deposition in water and in the active volume of a stereotactic diode field detector (SFD). Then, the RFs of the SFD were calculated for several circular field sizes and energies at 5 cm depth in water. Several low-energy photon spectra (mean energy 55 to 200 keV), as well as Co-60 radiation (mean energy 1.25 MeV) and a 6 MV Elekta Synergy beam (mean energy 2.9 MeV), in 10 × 10 cm2 field size were used to validate the MC calculations, using a simple beam model. The RFs of the SFD detector for a 6 MV Elekta Synergy linac photon beam in different field sizes were calculated. These were also measured with EBT3 Gafchromic film and the SFD detector. RESULTS: For the reference field size, differences between measured and calculated RFs were less than 5% at mean energies below 1 MeV and less than 1% at energies above 1 MeV. The calculated RFs for a 6 MV Elekta Synergy linac photon beam as a function of different field sizes showed a good agreement between the measurements and previously reported results. This agreement was within 2% for all considered field sizes. CONCLUSION: While at high photon energies, the change of response of the SFD is marginal, whereas it is extreme at low energies. Therefore, it is desirable to benchmark response calculations also in the low-energy domain. Our results, with a simple beam model and geometry, indicate that a validation of the simulations by experimental results is achievable. The present work provides a comprehensive table that can be used to calculate SFD detector response factors depending on both, field size and photon energy.

Improvement of the penumbra for small radiosurgical fields using flattening filter free low megavoltage beams.

BACKGROUND: In stereotactic radiosurgery, sharp beam edges have clear advantages to spare normal tissues. In general, the dose gradient is a limiting factor in minimizing dose to nearby critical structures for clinical cases. Therefore the penumbral width should be diminished. METHODS: A Varian Clinac 2100 linear accelerator equipped with in-house designed radiosurgical collimator was modeled using the EGSnrc/BEAMnrc Monte Carlo code and compared with the measurements. The 0.015 cm(3) PinPoint chamber was used to measure the 6 MV photon beam characteristics and to validate Monte Carlo calculations. Additional to the standard (STD) linac, a flattening filter free (FFF) linac was simulated. Percent depth doses, beam profiles and output factors were calculated for small field sizes with diameter of 5, 10, 20 and 30mm with DOSXYZnrc. The mean energy and photon fluence at the water surface were calculated with BEAMDP for both FFF linac and STD linacs. RESULTS: The penumbra width (80%-20%) was decreased by 0.5, 0.3, 0.2 and 0.2mm for field sizes of 5, 10, 20 and 30mm respectively when removing the FF. The fluence of photons at the surface increased up to 3.6 times and the mean energy decreased by a factor of 0.69 when removing the FF. The penumbra width (80%-20%) decreased by 17% when a 2 MeV monoenergetic electron pencil beam incident on the target is used instead of 6.2 MeV. CONCLUSIONS: It was found that the penumbra of small field sizes is decreased by removing the FF. Likewise using low megavoltage photons reduced the beam penumbra maintaining adequate penetration and skin sparing.

EBT GAFCHROMIC(TM) film dosimetry in compensator-based intensity modulated radiation therapy.

The electron benefit transfer (EBT) GAFCHROMIC films possess a number of features making them appropriate for high-quality dosimetry in intensity-modulated radiation therapy (IMRT). Compensators to deliver IMRT are known to change the beam-energy spectrum as well as to produce scattered photons and to contaminate electrons; therefore, the accuracy and validity of EBT-film dosimetry in compensator-based IMRT should be investigated. Percentage-depth doses and lateral-beam profiles were measured using EBT films in perpendicular orientation with respect to 6 and 18 MV photon beam energies for: (1) different thicknesses of cerrobend slab (open, 1.0, 2.0, 4.0, and 6.0 cm), field sizes (5×5, 10×10, and 20×20 cm(2)), and measurement depths (Dmax, 5.0 and 10.0 cm); and (2) step-wedged compensator in a solid phantom. To verify results, same measurements were implemented using a 0.125 cm(3) ionization chamber in a water phantom and also in Monte Carlo simulations using the Monte Carlo N-particle radiation transport computer code. The mean energy of photons was increased due to beam hardening in comparison with open fields at both 6 and 18 MV energies. For a 20×20 cm(2) field size of a 6 MV photon beam and a 6.0 cm thick block, the surface dose decreased by about 12% and percentage-depth doses increased up to 3% at 30.0 cm depth, due to the beam-hardening effect induced by the block. In contrast, at 18 MV, the surface dose increased by about 8% and depth dose reduced by 3% at 30.0 cm depth. The penumbral widths (80% to 20%) increase with block thickness, field size, and beam energy. The EBT film results were in good agreement with the ionization chamber dose profiles and Monte Carlo N-particle radiation transport computer code simulation behind the step-wedged compensator. Also, there was a good agreement between the EBT-film and the treatment-planning results on the anthropomorphic phantom. The EBT films can be accurately used as a 2D dosimeter for dose verification and quality assurance of compensator-based C-IMRT.

Development of novel strategies for the isolation of piglet testis cells with a high proportion of gonocytes.

Gonocytes have germline stem cell potential and are present in the neonatal testis, comprising 5-10% of freshly isolated testis cells. Maximising the number and proportion of gonocytes among freshly isolated testis cells will greatly facilitate their subsequent purification and in vitro study and manipulation. Seven experiments were conducted to evaluate the effects of multiple factors on the efficiency of testis cell isolation from neonatal pigs. We found that the use of a lysis buffer led to elimination of erythrocytes without adversely affecting testis cell isolation. Approximately ninefold as many live cells could be harvested by enzymatic digestion of testis tissues compared with mechanical methods. Digestion with collagenase-hyaluronidase-DNase followed by trypsin resulted in the highest recovery of live cells. However, the proportion of gonocytes ( approximately 7%) did not differ between the mechanical and enzymatic methods of testis cell isolation. Pretreatment of the tissue with cold enzymes increased the recovery of live testis cells. New strategies of combining a gentle enzymatic digestion with two rounds of vortexing resulted in the isolation of testis cells with very high gonocyte proportion. The efficiency of these novel methods could be further optimised to collect testis cells with a gonocyte proportion of approximately 40%. This novel three-step testis cell isolation strategy can be completed within 1 h and can harvest approximately 17 x 10(6) live gonocytes per g testis tissue. Therefore, in addition to elucidating the effects of several factors on testis cell isolation, we developed a novel strategy for the isolation of testis cells that yielded approximately 40% gonocytes in the freshly isolated cells (i.e. four- to eight-fold higher than the proportions obtained using current strategies). This strategy has instant applications in the purification of gonocytes.