JP4-039, a Mitochondria-Targeted Nitroxide, Mitigates the Effect of Apoptosis and Inflammatory Cell Migration in the Irradiated Mouse Retina.

We hypothesize that the injection of JP4-039, a mitochondria-targeted nitroxide, prior to irradiation of the mouse retina may decrease apoptosis and reduce neutrophil and macrophage migration into the retina. In our study, we aimed to examine the effects of JP4-039 in the mouse retina using fluorescent microscopy, a terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, and flow cytometry. Forty-five mice and one eye per mouse were used. In Group 1, fluorescent microscopy was used to determine retinal uptake of 10 µL (0.004 mg/µL) of intravitreally injected BODIPY-labeled JP4-039 at 0, 15, and 60 min after injection. In Group 2, the TUNEL assay was performed to investigate the rate of apoptosis after irradiation in addition to JP4-039 injection, compared to controls. In Group 3, flow cytometry was used to determine the extent of inflammatory cell migration into the retina after irradiation in addition to JP4-039 injection, compared to controls. Maximal retinal uptake of JP4-039 was 15 min after intravitreal injection (p < 0.0001). JP4-039-treated eyes had lower levels of retinal apoptosis (35.8 ± 2.5%) than irradiated controls (49.0 ± 2.7%; p = 0.0066) and demonstrated reduced migration of N1 cells (30.7 ± 11.7% vs. 77.7 ± 5.3% controls; p = 0.004) and M1 cells (76.6 ± 4.2 vs. 88.1 ± 3.7% controls, p = 0.04). Pretreatment with intravitreally injected JP4-039 reduced apoptosis and inflammatory cell migration in the irradiated mouse retina, marking the first confirmed effect of this molecule in retinal tissue. Further studies may allow for safety profiling and potential use for patients with radiation retinopathy.

Minimizing normal tissue low dose bath for left breast Volumetric Modulated Arc Therapy (VMAT) using jaw offset.

PURPOSE: With proper beam setup and optimization constraints in the treatment planning system, volumetric modulated arc therapy (VMAT) can improve target dose coverage and conformity while reducing doses to adjacent structures for whole breast radiation therapy. However, the low-dose bath effect on critical structures, especially the heart and the ipsilateral lung, remains a concern. In this study, we present a VMAT technique with the jaw offset VMAT (JO-VMAT) to reduce the leakage and scatter doses to critical structures for whole breast radiation therapy. MATERIALS AND METHODS: The data of 10 left breast cancer patients were retrospectively used for this study. CT images were acquired on a CT scanner (GE, Discovery) with the deep-inspiration breath hold (DIBH) technique. The planning target volumes (PTVs) and the normal structures (the lungs, the heart, and the contralateral breast) were contoured on the DIBH scan. A 3D field-in-field plan (3D-FiF), a tangential VMAT (tVMAT) plan, and a JO-VMAT plan were created with the Eclipse treatment planning system. An arc treatment field with the x-jaw closed across the central axis creates a donut-shaped high-dose distribution and a cylinder-shaped low-dose volume along the central axis of gantry rotation. Applying this setup with proper multi-leaf collimator (MLC) modulation, the optimized plan potentially can provide sufficient target coverage and reduce unnecessary irradiation to critical structures. The JO-VMAT plans involve 5-6 tangential arcs (3 clockwise arcs and 2-3 counterclockwise arcs) with jaw offsets. The plans were optimized with objective functions specified to achieve PTV dose coverage and homogeneity; For organs at risk (OARs), objective functions were specified individually for each patient to accomplish the best achievable treatment plan. For tVMAT plans, optimization constraints were kept the same except that the jaw offset was removed from the initial beam setup. The dose volume histogram (DVH) parameters were generated for dosimetric evaluation of PTV and OARs. RESULTS: The D95% to the PTV was greater than the prescription dose of 42.56 Gy for all the plans. With both VMAT techniques, the PTV conformity index (CI) was statistically improved from 0.62 (3D-FiF) to 0.83 for tVMAT and 0.84 for JO-VMAT plans. The difference in the homogeneity index (HI) was not significant. The Dmax to the heart was reduced from 12.15 Gy for 3D-FiF to 8.26 Gy for tVMAT and 7.20 Gy for JO-VMAT plans. However, a low-dose bath effect was observed with tVMAT plans to all the critical structures including the lungs, the heart, and the contralateral breast. With JO-VMAT, the V5Gy and V2Gy of the heart were reduced by 32.7% and 15.4% compared to 3D-FiF plans. Significantly, the ipsilateral lung showed a reduction in mean dose (4.65-3.44 Gy) and low dose parameters (23.4% reduction for V5Gy and 10.7% reduction for V2Gy) for JO-VMAT plans compared to the 3D-FiF plans. The V2Gy dose to the contralateral lung and breast was minimal with JO-VMAT techniques. CONCLUSION: A JO-VMAT technique was evaluated in this study and compared with 3D-FiF and tVMAT techniques. Our results showed that the JO-VMAT technique can achieve clinically comparable coverage and homogeneity and significantly improve dose conformity within PTV. Additionally, JO-VMAT eliminated the low-dose bath effect at all OARs evaluation metrics including the ipsilateral/contralateral lung, the heart, and the contralateral breast compared to 3D-FiF and tVMAT. This technique is feasible for the whole breast radiation therapy of left breast cancers.

Evaluating intra-fractional tumor motion in lung stereotactic radiotherapy with deep inspiration breath-hold.

PURPOSE: To evaluate the intra-fractional tumor motion in lung stereotactic body radiotherapy (SBRT) with deep inspiration breath-hold (DIBH), and to investigate the adequacy of the current planning target volume (PTV) margins. METHODS: Twenty-eight lung SBRT patients with DIBH were selected in this study. Among the lesions, twenty-three were at right or left lower lobe, two at right middle lobe, and three at right or left upper lobe. Post-treatment gated cone-beam computed tomography (CBCT) was acquired to quantify the intra-fractional tumor shift at each treatment. These obtained shifts were then used to calculate the required PTV margin, which was compared with the current applied margin of 5 mm margin in anterior-posterior (AP) and right-left (RL) directions and 8 mm in superior-inferior (SI) direction. The beam delivery time was prolonged with DIBH. The actual beam delivery time with DIBH (Tbeam_DIBH) was compared with the beam delivery time without DIBH (Tbeam_wo_DIBH) for the corresponding SBRT plan. RESULTS: A total of 113 treatments were analyzed. At six treatments (5.3%), the shifts exceeded the tolerance defined by the current PTV margin. The average shifts were 0.0 ± 1.9 mm, 0.1±1.5 mm, and -0.5 ± 3.7 mm in AP, RL, and SI directions, respectively. The required PTV margins were determined to be 4.5, 3.9, and 7.4 mm in AP, RL, and SI directions, respectively. The average Tbeam_wo_DIBH and Tbeam_DIBH were 2.4 ± 0.4 min and 3.6 ± 1.5 min, respectively. The average treatment slot for lung SBRT with DIBH was 25.3 ± 7.9 min. CONCLUSION: Intra-fractional tumor motion is the predominant source of treatment uncertainties in CBCT-guided lung SBRT with DIBH. The required PTV margin should be determined based on data specific to each institute, considering different techniques and populations. Our data indicate that our current applied PTV margin is adequate, and it is possible to reduce further in the RL direction. The time increase of Tbeam_DIBH, relative to the treatment slot, is not clinically significant.

Genetically Engineered Probiotic Limosilactobacillus reuteri Releasing IL-22 (LR-IL-22) Modifies the Tumor Microenvironment, Enabling Irradiation in Ovarian Cancer.

Despite recent advances in cancer therapy, ovarian cancer remains the most lethal gynecological cancer worldwide, making it crucial and of the utmost importance to establish novel therapeutic strategies. Adjuvant radiotherapy has been assessed historically, but its use was limited by intestinal toxicity. We recently established the role of Limosilactobacillus reuteri in releasing IL-22 (LR-IL-22) as an effective radiation mitigator, and we have now assessed its effect in an ovarian cancer mouse model. We hypothesized that an LR-IL-22 gavage would enable intestinal radioprotection by modifying the tumor microenvironment and, subsequently, improving overall survival in female C57BL/6MUC-1 mice with widespread abdominal syngeneic 2F8cis ovarian cancer. Herein, we report that the LR-IL-22 gavage not only improved overall survival in mice when combined with a PD-L1 inhibitor by inducing differential gene expression in irradiated stem cells but also induced PD-L1 protein expression in ovarian cancer cells and mobilized CD8+ T cells in whole abdomen irradiated mice. The addition of LR-IL-22 to a combined treatment modality with fractionated whole abdomen radiation (WAI) and systemic chemotherapy and immunotherapy regimens can facilitate a safe and effective protocol to reduce tumor burden, increase survival, and improve the quality of life of a locally advanced ovarian cancer patient.

On dosimetric characteristics of detectors for relative dosimetry in small fields: a multicenter experimental study.

Objective. In this multicentric collaborative study, we aimed to verify whether the selected radiation detectors satisfy the requirements of TRS-483 Code of Practice for relative small field dosimetry in megavoltage photon beams used in radiotherapy, by investigating four dosimetric characteristics. Furthermore, we intended to analyze and complement the recommendations given in TRS-483.Approach. Short-term stability, dose linearity, dose-rate dependence, and leakage were determined for 17 models of detectors considered suitable for small field dosimetry. Altogether, 47 detectors were used in this study across ten institutions. Photon beams with 6 and 10 MV, with and without flattening filters, generated by Elekta Versa HDTMor Varian TrueBeamTMlinear accelerators, were used.Main results. The tolerance level of 0.1% for stability was fulfilled by 70% of the data points. For the determination of dose linearity, two methods were considered. Results from the use of a stricter method show that the guideline of 0.1% for dose linearity is not attainable for most of the detectors used in the study. Following the second approach (squared Pearson's correlation coefficientr2), it was found that 100% of the data fulfill the criteriar2> 0.999 (0.1% guideline for tolerance). Less than 50% of all data points satisfied the published tolerance of 0.1% for dose-rate dependence. Almost all data points (98.2%) satisfied the 0.1% criterion for leakage.Significance. For short-term stability (repeatability), it was found that the 0.1% guideline could not be met. Therefore, a less rigorous criterion of 0.25% is proposed. For dose linearity, our recommendation is to adopt a simple and clear methodology and to define an achievable tolerance based on the experimental data. For dose-rate dependence, a realistic criterion of 1% is proposed instead of the present 0.1%. Agreement was found with published guidelines for background signal (leakage).

Inverse shielding and mutual exclusion for PET-MR hybrid imaging concerning induced positronium hyperfine splits radiations.

Prevalent PET imaging reconstructs 2γ-photon pairs emitted after an annihilation from para-positronium (p-Ps) and rejects 3γ events from ortho-positronium (o-Ps) as noises. The 3γ/2γ decay ratio is ~ 3/7 in human body theoretically but in fact significantly lower due to pick-off process, hence PET imaging quality is well controlled. In a PET-MR hybrid unit, the MR magnetic field alters positronium decay patterns through magnetic quenching: all o-Ps and excited p-Ps states are split into finer quantum states under strong magnetic field, thus transitions between some triplet and singlet finer states (mz = 0) were no longer forbidden, thus some o-Ps converts to p-Ps spontaneously by emitting hyperfine split (HFS) photons, which also drops 3γ/2γ ratio hence helps PET imaging quality. However, inverse magnetic quenching might also occur if any external source of HFS frequencies is nearby, thus many p-Ps convert to o-Ps by absorbing those HFS photons (induced HFS transitions). This will dramatically increase 3γ/2γ ratio and hence degrade PET imaging quality instantaneously. The HFS spectrum lies in a broad range of microwaves, from 0.02 to 200 GHz. To prevent inverse magnetic quenching, it is necessary to block external microwave sources outside the hybrid vault, by adding a thin metal layer at all directions of the vault. This could be achieved by adopting the metallic Faraday Cage, which was originally for MR shielding, with possible amendment if necessary. The frequencies of excitation pulses in MR imaging overlap with HFS spectrum, however, the chance for mutual interference during hybrid imaging is small, hence there seems no need to veto each other during hybrid scans.

Chemical Carcinogen (Dimethyl-benzanthracene) Induced Transplantable Cancer in Fanconi Anemia (Fanca-/-) Mice.

BACKGROUND/AIM: Patients with radiation sensitive Fanconi anemia (FA) are presenting with cancers of the oral cavity, oropharynx, and other anatomic locations. MATERIALS AND METHODS: Animal models for cancer in FA mice used orthotopic tumors from wild type mice. We derived a cancer cell line from Fanca-/- mice by topical application of the chemical carcinogen dimethyl benzanthracene (DMBA). RESULTS: A Fanca-/- mouse rhabdomyosarcoma was derived from a Fanca-/- (129/Sv) mouse. The in vitro clonogenic survival of the Fanca-/- clone 6 cancer cell line was consistent with the FA genotype. Transplanted tumors demonstrated hypoxic centers surrounded by senescent cells. CONCLUSION: This Fanca-/- mouse syngeneic cancer should provide a valuable resource for discovery and development of new normal tissue radioprotectors for patients with FA and cancer.

Study on Blood Pressure, e-GFR, Serum Albumin, C-reactive Protein in Normal Subjects and Patients with CKD.

In general, Kidney diseases are silent with no apparent early symptoms and chronic kidney disease (CKD) is marked by gradual loss of kidney function over time. High rate of inflammation is common in CKD and it causes high CRP level. High CRP levels are associated with low e-GFR and low serum albumin level. This study was conducted to determine the changes of blood pressure, estimated glomerular filtration rate, serum albumin and C-reactive protein in chronic kidney diseased patients and compared with healthy subjects. This analytical type of cross sectional study was carried out in the Department of Physiology, Mymensingh Medical College, Bangladesh from July 2021 to June 2022. A total number of 140 subjects, age range between 25-70 years were included in this study. Among them, 70 healthy subjects were taken as control group (Group I) with 35 male (IA) and 35 female (IB) and 70 chronic kidney diseased patients were taken as study group (Group II) with 35 male (IIA) and 35 female (IIB). Calculation of estimated glomerular filtration rate (eGFR) was done by chronic kidney disease epidemiology collaboration (CKD-EPI) equation. Data were expressed as mean±SD and statistical significance difference among the group were calculated by unpaired t-test. In this study, we found that eGFR (in IIA 29.83±0.73 ml/min and in IIB 30.80±0.73ml/min) and serum albumin (in IIA 2.96±0.04g/dl in IIB 2.07±0.02g/dl) were significantly decreased in study group in comparison to control group. Blood pressure (SBP in IIA 150.57±1.70 mm of Hg, in IIB 143.71±1.32 mm of Hg and DBP in IIA 94.40±0.70 and in IIB 91.20±0.70 mm of Hg) and C-reactive protein (CRP) (in IIA 12.14±0.90mg/l and in IIB 21.80±2.58mg/l) were significantly increased in study group in comparison to control group. CKD is associated with increased risks of several co-morbidities including cardiovascular complications and chronic renal failure. Detection of CKD at an early stage helps to reduce the progression of renal disease and burden of end stage renal disease.

Status of Serum Iron and Fasting Serum Glucose in Reproductive Aged Women Taking Combined Oral Contraceptive Pill.

The oral contraceptive pill, 'the pill', was introduced in the beginning of the 1960s. Presently, worldwide about 100 million women are current users of combined oral hormonal contraceptives (COC) most frequently used in the western world. Oral contraceptive use has been associated with decreased menstrual blood losses; thus, can independently reduce the risk of anemia and iron deficiency in women. Manufacturers have recently started to include supplemental iron in the non-hormonal placebo tablets of some contraceptives. This study was done to evaluate the status of serum iron and fasting serum glucose in combined oral contraceptive pill users in comparison to non-users. This cross sectional study was carried out in the Department of Physiology, Mymensingh Medical College, Bangladesh from July 2021 to June 2022. A total number of 120 reproductive aged women, age ranged from 15-55 years was included in this study. Among them, sixty (60) combined oral contraceptive pill users subjects were taken as study group (Group II) and sixty (60) age matched oral pill non users subjects were taken as control group (Group I). Data were expressed as mean±SD and statistical significance of difference among the group was calculated by unpaired students' 't' test. The mean±SD of serum iron of control group (Group I) and study group (Group II) were 93.22±17.19µg/dl and 181.57±22.06µg/dl respectively. The mean±SD of fasting serum glucose of control group (Group I) and study group (Group II) were 4.67±0.61mmol/L and 6.61±0.61mmol/L respectively. Serum iron and fasting serum glucose increased in study group in comparison to control group. Result is statistically highly significant (p<0.001). So there from this study it can be concluded that there is significant association of serum iron and fasting serum glucose with oral contraceptives.

Inhibition of tyrosine kinase Fgr prevents radiation-induced pulmonary fibrosis (RIPF).

Cellular senescence is involved in the development of pulmonary fibrosis as well as in lung tissue repair and regeneration. Therefore, a strategy of removal of senescent cells by senolytic drugs may not produce the desired therapeutic result. Previously we reported that tyrosine kinase Fgr is upregulated in ionizing irradiation-induced senescent cells. Inhibition of Fgr reduces the production of profibrotic proteins by radiation-induced senescent cells in vitro; however, a mechanistic relationship between senescent cells and radiation-induced pulmonary fibrosis (RIPF) has not been established. We now report that senescent cells from the lungs of mice with RIPF, release profibrotic proteins for target cells and secrete chemotactic proteins for marrow cells. The Fgr inhibitor TL02-59, reduces this release of profibrotic chemokines from the lungs of RIPF mice, without reducing numbers of senescent cells. In vitro studies demonstrated that TL02-59 abrogates the upregulation of profibrotic genes in target cells in transwell cultures. Also, protein arrays using lung fibroblasts demonstrated that TL02-59 inhibits the production of chemokines involved in the migration of macrophages to the lung. In thoracic-irradiated mice, TL02-59 prevents RIPF, significantly reduces levels of expression of fibrotic gene products, and significantly reduces the recruitment of CD11b+ macrophages to the lungs. Bronchoalveolar lavage (BAL) cells from RIPF mice show increased Fgr and other senescent cell markers including p16. In human idiopathic pulmonary fibrosis (IPF) and in RIPF, Fgr, and other senescent cell biomarkers are increased. In both mouse and human RIPF, there is an accumulation of Fgr-positive proinflammatory CD11b+ macrophages in the lungs. Thus, elevated levels of Fgr in lung senescent cells upregulate profibrotic gene products, and chemokines that might be responsible for macrophage infiltration into lungs. The detection of Fgr in senescent cells that are obtained from BAL during the development of RIPF may help predict the onset and facilitate the delivery of medical countermeasures.

Release of Interferon-ß (IFN-ß) from Probiotic Limosilactobacillus reuteri-IFN-ß (LR-IFN-ß) Mitigates Gastrointestinal Acute Radiation Syndrome (GI-ARS) following Whole Abdominal Irradiation.

Irradiation can be an effective treatment for ovarian cancer, but its use is limited by intestinal toxicity. Thus, strategies to mitigate toxicity are important and can revitalize the current standard of care. We previously established that LR-IL-22 protects the intestine from WAI. We now hypothesize that LR-IFN-ß is an effective radiation protector and mitigator and is rapidly cleared from the digestive tract, making it an option for intestinal radioprotection. We report that the gavage of LR-IFN-ß during WAI provides improved intestinal barrier integrity and significantly preserves the numbers of Lgr5+GFP+ intestinal stem cells, improving survival. The rapid clearance of the genetically engineered probiotic from the digestive tract renders it a safe and feasible radiation mitigator. Therefore, the above genetically engineered probiotic is both a feasible and effective radiation mitigator that could potentially revolutionize the management of OC patients. Furthermore, the subsequent addition of platinum/taxane-based chemotherapy to the combination of WAI and LR-IFN-ß should reduce tumor volume while protecting the intestine and should improve the overall survival in OC patients.

A novel approach to infectious disease control and radiotherapy risk management.

BACKGROUND: Infectious disease outbreaks have always presented challenges to the operation of healthcare systems. In particular, the treatment of cancer patients within Radiation Oncology often cannot be delayed or compromised due to infection control measures. Therefore, there is a need for a strategic approach to simultaneously managing infection control and radiotherapy risks. PURPOSE: To develop a systematic risk management method that uses mathematical models to design mitigation efforts for control of an infectious disease outbreak, while ensuring safe delivery of radiotherapy. METHODS: A two-stage failure mode and effect analysis (FMEA) approach is proposed to modify radiotherapy workflow during an infectious disease outbreak. In stage 1, an Infection Control FMEA (IC-FMEA) is conducted, where risks are evaluated based on environmental parameters, clinical interactions, and modeling of infection risk. occupancy risk index (ORI) is defined as a metric for infection transmission risk level in each room, based on the degree of occupancy. ORI, in combination with ventilation rate per person (Rp ), is used to provide a broad infection risk assessment of workspaces. For detailed IC-FMEA of clinical processes, infection control failure mode (ICFM) is defined to be any instance of disease transmission within the clinic. Infection risk priority number (IRPN) has been formulated as a function of time, distance, and degree of protective measures. Infection control measures are then systematically integrated into the workflow. Since the workflow is perturbed by infection control measures, there is a possibility of introducing new radiotherapy failure modes or increased likelihood of existing failure modes. Therefore, in stage 2, a conventional radiotherapy FMEA (RT-FMEA) should be performed on the adjusted workflow. RESULTS: The COVID-19 pandemic was used to illustrate stage 1 IC-FMEA. ORI and Rp values were calculated for various workspaces within a clinic. A deep inspiration breath hold (DIBH) CT simulation was used as an example to demonstrate detailed IC-FMEA with ICFM identification and IRPN evaluation. A total of 90 ICFMs were identified in the DIBH simulation process. The calculated IRPN values were found to be progressively decreasing for workflows with minimal, moderate, and enhanced levels of protective measures. CONCLUSION: The framework developed in this work provides tools for radiotherapy clinics to systematically assess risk and adjust workflows during the evolving circumstances of any infectious disease outbreak.

Evaluate the Changes of Body Mass Index and Blood Pressure in Combined Oral Contraceptive Pill Users.

The oral contraceptive pill, 'the pill', was introduced in the starting of the 1960s. Presently, worldwide about 100 million women are current users of combined hormonal contraceptives (COC) most frequently used in the western world. The most frequently used agents are a combination of drugs containing both the estrogen and progesterone. This combination is considered to be highly efficacious, generally considered 99.9% and a use effectiveness of 97.0% to 98.0%. This study was done to evaluate the changes of Body Mass Index (BMI) and Blood pressure ( BP) in combined oral contraceptive pill users in comparison to non- users. This cross sectional study was carried out in the Department of Physiology, Mymensingh Medical College, Mymensingh, Bangladesh from July 2021 to June 2022. Total number of 120 reproductive aged women, age ranged from 15-55 years was included in this study. Among them, sixty (60) combined oral contraceptive pill users subjects were taken as study group (Group II) and sixty (60) age matched oral pill non users subjects were taken as control group (Group I). Data were expressed as mean±SD and statistical significance of difference among the group was calculated by unpaired students' 't' test and Pearson's correlation coefficient test. The mean±SD of BMI of control group (Group I) and study group (Group II) were 22.50±1.50 kg/m² and 27.64±1.28 kg/m² respectively. In study group (Group II) BMI was increased. Result is statistically highly significant (p<0.001). The mean±SD of systolic blood pressure of control group (Group I) and study group (Group II) were 111.17±8.51 mm of Hg and 127.50±6.14 mm of Hg respectively. In this study the mean±SD of diastolic blood pressure of control group (Group I and study group (Group II) were 75.58±5.05mm of Hg and 87.00±4.89 mm of Hg respectively. In study group (Group II) diastolic blood pressure was increased. Result is statistically highly significant (p<0.001). So the assessment of this parameter is important for early detection and prevention of complication related to combined oral contraceptive pill use for leading a healthy life.

A Comparative Study of Body Mass Index and Blood Pressure between Sedentary and Non-Sedentary Workers.

Sedentary lifestyle are spreading worldwide because of lack of available spaces for exercise, increased occupational sedentary behaviors such as office work and the increased prevalence of television and video devices. Increased incidence of sedentary lifestyle and obesity in developed and developing countries is one of the major risk factors for the development of cardiovascular diseases. This study was undertaken to analyze the differences in anthropometric and cardiovascular parameters in sedentary and non-sedentary male subjects. This analytical type of cross sectional study was carried out in the Department of Physiology, Mymensingh Medical College, Mymensingh, Bangladesh from July 2021 to June 2022. This study consisted 50 male employees of 25-60 years who worked in an office were study group (Group II) and control group Group-I) consisted of 50 male age matched physical laborers. BMI was calculated as weight in kilogram divided by the height in meter square i.e. kg/m². Blood Pressure was measured by indirect auscultatory method with an aneroid sphygmomanometer. Statistical analysis was done by using Student's un-paired 't' test. Values expressed as mean ± standard deviation. P value was taken as significant at 5 percent confidence level. The mean±SD BMI in kg/m² of Group I and Group II were 21.90±2.22 and 29.32±3.13 respectively. The mean±SD systolic blood pressure of Group I and Group II were 112.20±6.79 and 145.10±8.11 and mean±SD diastolic blood pressure of Group I and Group II were 72.80±5.73 and 91.00±5.05 respectively. The BMI and blood pressure were increased in sedentary group compared to non-sedentary group. From the study, it appears that the risk for cardiovascular disease is increased in sedentary workers.

Portal dosimetry correction method for validation of single isocenter VMAT plans for multiple brain metastases.

Portal dosimetry is one option for verification of volumetric-modulated arc therapy (VMAT) planning for multiple brain metastases. However, due to the changing response of the portal imager with photon beam energy, the dose transmitted through closed multileaf collimator (MLC) leaves or narrow MLC gaps may be underestimated by the imager. We present a simple method for correcting for these effects that may be implemented within the Eclipse treatment planning system. We recalculated the predicted portal dose with and without this correction for 20 multiple brain met VMAT plans. Before the correction, 3/20 composite plan fields passed our standard quality assurance (QA) criteria (54/80 individual fields); the average gamma passing rate for the composite plans was 76.9 ± 16.6%, and the average gamma value across the composite plans was 0.67 ± 0.23. After correction, 20/20 composite plan fields passed the QA criteria (80/80 individual fields); the average gamma passing rate for composite plans was 99.2 ± 1.4%, the average gamma value across the composite plans was 0.33 ± 0.90. A measure of plan complexity, the average leaf pair opening could be correlated to the gamma analysis results for the uncorrected plans but not for the corrected plans.

A multi-institutional evaluation of small field output factor determination following the recommendations of IAEA/AAPM TRS-483.

PURPOSE: The aim of this work was to test the implementation of small field dosimetry following TRS-483 and to develop quality assurance procedures for the experimental determination of small field output factors (SFOFs). MATERIALS AND METHODS: Twelve different centers provided SFOFs determined with various detectors. Various linac models using the beam qualities 6 MV and 10 MV with flattening filter and without flattening filter were utilized to generate square fields down to a nominal field size of 0.5 cm × 0.5 cm. The detectors were positioned at 10 cm depth in water. Depending on the local situation, the source-to-surface distance was either set to 90 cm or 100 cm. The SFOFs were normalized to the output of the 10 cm × 10 cm field. The spread of SFOFs measured with different detectors was investigated for each individual linac beam quality and field size. Additionally, linac-type specific SFOF curves were determined for each beam quality and the SFOFs determined using individual detectors were compared to these curves. Example uncertainty budgets were established for a solid state detector and a micro ionization chamber. RESULTS: The spread of SFOFs for each linac and field was below 5% for all field sizes. With the exception of one linac-type, the SFOFs of all investigated detectors agreed within 10% with the respective linac-type SFOF curve, indicating a potential inter-detector and inter-linac variability. CONCLUSION: Quality assurance on the SFOF measurements can be done by investigation of the spread of SFOFs measured with multiple detectors and by comparison to linac-type specific SFOFs. A follow-up of a measurement session should be conducted if the spread of SFOFs is larger than 5%, 3%, and 2% for field sizes of 0.5 cm × 0.5 cm, 1 cm × 1 cm, and field sizes larger than 2 cm × 2 cm, respectively. Additionally, deviations of measured SFOFs to the linac-type-curves of more than 7%, 3%, and 2% for field sizes 0.5 cm × 0.5 cm, 1 cm × 1 cm, and field sizes larger than 1 cm × 1 cm, respectively, should be followed up.

Intestinal Radiation Protection and Mitigation by Second-Generation Probiotic Lactobacillus-reuteri Engineered to Deliver Interleukin-22.

(1) Background: The systemic administration of therapeutic agents to the intestine including cytokines, such as Interleukin-22 (IL-22), is compromised by damage to the microvasculature 24 hrs after total body irradiation (TBI). At that time, there is significant death of intestinal microvascular endothelial cells and destruction of the lamina propria, which limits drug delivery through the circulation, thus reducing the capacity of therapeutics to stabilize the numbers of Lgr5+ intestinal crypt stem cells and their progeny, and improve survival. By its direct action on intestinal stem cells and their villus regeneration capacity, IL-22 is both an ionizing irradiation protector and mitigator. (2) Methods: To improve delivery of IL-22 to the irradiated intestine, we gavaged Lactobacillus-reuteri as a platform for the second-generation probiotic Lactobacillus-reuteri-Interleukin-22 (LR-IL-22). (3) Results: There was effective radiation mitigation by gavage of LR-IL-22 at 24 h after intestinal irradiation. Multiple biomarkers of radiation damage to the intestine, immune system and bone marrow were improved by LR-IL-22 compared to the gavage of control LR or intraperitoneal injection of IL-22 protein. (4) Conclusions: Oral administration of LR-IL-22 is an effective protector and mitigator of intestinal irradiation damage.

A detailed process map for clinical workflow of a new biology-guided radiotherapy (BgRT) machine.

PURPOSE: Biology-guided radiotherapy (BgRT) is a new external beam radiation therapy modality combining PET-CT with a linear accelerator that has the potential to track and treat one or more tumors in real-time. The use of PET and radiopharmaceutical tracers introduces new processes that are different from the existing treatment processes. In this study, we have developed a process map for the clinical implementation of a prototype BgRT machine. METHODS: A team of 13 members from various radiation therapy disciplines at our institution participated in developing a prospective process map for a prototype BgRT machine. The methodology provided by the AAPM TG 100 report was followed. In particular, the steps unique to the BgRT workflow, using hypofractionated stereotactic body radiation therapy with fluorodeoxyglucose radiolabeled with fluorine-18 (FDG) to guide beam delivery, were analyzed. RESULTS: The multi-disciplinary team in the department of radiation oncology at our institution developed a prospective process map for the clinical BgRT workflow. By focusing on the appropriate level of detail, 15 major subprocesses, 133 steps, and 248 substeps were identified and the process map was agreed upon as being useful, implementable, and manageable. Seventy-four steps from nine subprocesses, 55.6% of the whole process, were analyzed to be the BgRT unique steps. They originate mainly from: (1) acquiring multiple PET images at the BgRT machine with separate patient visits, (2) creating a unique biological treatment volume for BgRT plan (PTVBgRT ), and (3) BgRT plan optimization and treatment delivery using PET images. CONCLUSION: Using BgRT to irradiate multiple metastases in the same session will impact clinical workflow, thus a graphical process map depicting the new clinical workflow with an appropriate level of detail is critical for efficient, safe, and high-quality care. The prospective process map will guide the successful setup and use of the new BgRT system.

Lactobacillus reuteri Releasing IL-22 (LR-IL-22) Facilitates Intestinal Radioprotection for Whole-Abdomen Irradiation (WAI) of Ovarian Cancer.

Oral administration (gavage) of a second-generation probiotic, Lactobacillus reuteri (L. reuteri), that releases interleukin-22 (LR-IL-22) at 24 h after total-body irradiation (TBI) mitigates damage to the intestine. We determined that LR-IL-22 also mitigates partial-body irradiation (PBI) and whole-abdomen irradiation (WAI). Irradiation can be an effective treatment for ovarian cancer, but its use is limited by intestinal toxicity. Strategies to mitigate toxicity are important and can revitalize this modality to treat ovarian cancer. In the present studies, we evaluated whether LR-IL-22 facilitates fractionated WAI in female C57BL/6 mice with disseminated ovarian cancer given a single fraction of either 15.75 Gy or 19.75 Gy or 4 daily fractions of 6 Gy or 6.5 Gy. Mice receiving single or multiple administrations of LR-IL-22 during WAI showed improved intestinal barrier integrity (P = 0.0167), reduced levels of radiation-induced intestinal cytokines including KC/CXCL1 (P = 0.002) and IFN-γ (P = 0.0024), and reduced levels of plasma, Eotaxin/CCL11 (P = 0.0088). LR-IL-22 significantly preserved the numbers of Lgr5+GFP+ intestinal stem cells (P = 0.0010) and improved survival (P < 0.0343). Female C57BL/6MUC-1 mice with widespread abdominal syngeneic 2F8cis ovarian cancer that received LR-IL-22 during 6.5 Gy WAI in 4 fractions had reduced tumor burden, less intestinal toxicity, and improved 30-day survival. Furthermore, LR-IL-22 facilitated WAI when added to Paclitaxel and Carboplatin chemotherapy and further increased survival. Oral administration (gavage) of LR-IL-22 is a potentially valuable intestinal radioprotector, which can facilitate therapeutic WAI for widespread intra-abdominal ovarian cancer.