An in-vivo study of the combined therapeutic effects of pulsed non-thermal focused ultrasound and radiation for prostate cancer.

PURPOSE: The purpose of this study was to investigate the in vivo combined effects of pulsed focused ultrasound (pFUS) and radiation (RT) for prostate cancer treatment. MATERIALS AND METHODS: An animal prostate tumor model was developed by implanting human LNCaP tumor cells in the prostates of nude mice. Tumor-bearing mice were treated with pFUS, RT or both (pFUS + RT) and compared with a control group. Non-thermal pFUS treatment was delivered by keeping the body temperature below 42 °C as measured real-time by MR thermometry and using a pFUS protocol (1 MHz, 25 W focused ultrasound; 1 Hz pulse rate with a 10% duty cycle for 60 sec for each sonication). Each tumor was covered entirely using 4-8 sonication spots. RT treatment with a dose of 2 Gy was delivered using an external beam (6 MV photon energy with dose rate 300MU/min). Following the treatment, mice were scanned weekly with MRI for tumor volume measurement. RESULTS: The results showed that the tumor volume in the control group increased exponentially to 142 ± 6%, 205 ± 12%, 286 ± 22% and 410 ± 33% at 1, 2, 3 and 4 weeks after treatment, respectively. In contrast, the pFUS group was 29% (p < 0.05), 24% (p < 0.05), 8% and 9% smaller, the RT group was 7%, 10%, 12% and 18% smaller, and the pFUS + RT group was 32%, 39%, 41% and 44% (all with p < 0.05) smaller than the control group at 1, 2, 3, and 4 weeks post treatment, respectively. Tumors treated by pFUS showed an early response (i.e. the first 2 weeks), while the RT group showed a late response. The combined pFUS + RT treatment showed consistent response throughout the post-treatment weeks. CONCLUSIONS: These results suggest that RT combined with non-thermal pFUS can significantly delay the tumor growth. The mechanism of tumor cell killing between pFUS and RT may be different. Pulsed FUS shows early tumor growth delay, while RT contributes to the late effect on tumor growth delay. The addition of pFUS to RT significantly enhanced the therapeutic effect for prostate cancer treatment.

2D IMRT QA passing rate dependency on coronal plane.

Intensity modulated radiation therapy (IMRT) delivery involves a complex series of beam angles and multileaf collimator (MLC) arrangements, requiring quality assurance to be performed to validate delivery before treatment. The purpose of this work is to investigate the effect of dose gradient on quality assurance (QA) passing rate. Many (n = 40) IMRT plans were delivered and measured using a 2D planar array of ion chambers; additionally, eleven plans were measured at several coronal planes. For each measurement, dose gradient was assessed using a number of metrics and passing rate assessed at both 3%/3 mm and 3%/2 mm criteria. The passing rates of the various IMRT plans were shown to be generally correlated to gradient, with an average distance correlation of 0.54 ± 0.04 for the lateral dose gradient. The passing rate for an individual plan was shown to vary with coronal slice, though the correlation to dose gradient was not predictable. Even though the passing rate was strongly related to dose gradient for many of the plans, the signs of the correlations were not always negative, as hypothesized. The coronal plane at which QA is performed affects passing rate, though dose gradient may not easily be used to predict slices at which passing rate is higher.

A new target localization method for image-guided radiation therapy of prostate cancer.

In imaged-guided radiation therapy (IGRT), target localization is usually done with rigid-body registration based on anatomy matching. Problems arise when the target volume can only be matched partially due to inter-fractional organ motion and deformation, resulting in deteriorated target coverage and critical structure sparing. A new target localization method is investigated in which the treatment target volume is aligned with the prescription isodose surface. Our study included 15 prostate patients previously treated with intensity-modulated radiation therapy (IMRT). Patient setup and target localization were performed using a CT-on-rails system before and after the IMRT treatment. IMRT plans were generated on the original simulation CTs (15) and the same MUs and leaf sequences were used to compute the dose distributions on post-treatment CTs (98) with the isocenter adjustments based on either anatomical structure matching or prescription isodose surface alignment. When patients were aligned with the traditional anatomy matching method, the dose to 95% of the CTV, D95, received 74.0 - 77.6 Gy and the minimum CTV dose, Dmin, was 61.9 - 71.6 Gy, respectively, in the cumulative dose distributions. The rectal dose-volume constraints were violated in 35.7% of the treatment fractions. When patients were aligned using the new localization method, the dose to 95% of the CTV, D95, received 74.0 - 78.2 Gy and the minimum CTV dose, Dmin, was 68.4 - 71.6 Gy, respectively, in the cumulative dose distributions. The rectal dose-volume constraints were violated in 17.3% of the treatment fractions. Traditional IGRT target localization based on anatomy matching is effective for population-based PTV margins but not ideal for those patients with large inter-fractional prostate rotation/deformation due to large rectal and bladder volume variation. The new method using the prescription isodose surface to align the target volume could improve the target coverage and rectal sparing for these patients, which can be implemented clinically to improve target dose delivery accuracy.

Therapeutic effects of in-vivo radiodynamic therapy (RDT) for lung cancer treatment: a combination of 15MV photons and 5-aminolevulinic acid (5-ALA).

Objective.Radiodynamic therapy (RDT) uses high-energy photon beams instead of visible/near-infrared light to treat deep-seated tumors that photodynamic therapy cannot achieve due to the low penetration depth of laser beams. The purpose of this study is to investigate the therapeutic effect of RDT with 15 MV photon beams combined with 5-aminolevulinic acid (5-ALA) using a mouse model.Approach.A subcutaneous C57BL/6 mouse model of KP1 small-cell lung cancer cell line was used. The tumors (N = 120) were randomized into four groups to observe individual and synergistic effects of 5-ALA and radiation treatment: control (untreated, N = 42), radiation treatment (RT) only (N = 20), 5-ALA only (N = 20), and RDT (N = 38). For the RT only and RDT groups, 4 Gy in a single fraction was delivered to the tumors using 15 MV photons. For the 5-ALA only and RDT groups, 5-ALA was injected at a dose of 100 mg kg-1by tail-vein 4 h prior to RT. The tumor response was assessed by monitoring tumor growth using 1.5 T MR, maximum standardized uptake value (SUVmax) and total lesion glycolysis (TLG) using [18F]FDG PET/CT, and animal survival.Main results.RDT achieved a statistically significant delay in tumor growth by 52.1%, 48.1%, and 57.9% 7 days post-treatment compared to 5-ALA only, RT only, and control group (P < 0.001), respectively. There were no significant differences in tumor growth between 5-ALA only and RT only groups. An additional 38.5%-40.9% decrease in tumor growth was observed, showing a synergistic effect with RDT. Furthermore, RDT significantly decreased [18F]FDG uptakes in SUVmaxand TLG 7 days post-treatment by 47.4% and 66.5% (P < 0.001), respectively. RDT mice survived the longest of all treatment groups.Significance.RDT with 15 MV photons and 5-ALA resulted in greater tumor control compared to the control and other treatment groups. A significant synergistic effect was also observed with RDT. These preliminary results demonstrate an effective cancer treatment modality.

Evaluating suggested stricter gamma criteria for linac-based patient-specific delivery QA in the conventional and SBRT environments.

PURPOSE: To evaluate AAPM TG-218 recommended tolerances for IMRT QA for conventional and SBRT delivery. METHODS: QA analysis was repeated for 150 IMRT/VMAT patients with varying gamma criteria. True composite delivery was utilized, corrected for detector and output variation. Universal tolerance (TLuniv) and action limits (ALuniv) were compared with statistical process control (SPC) TLSPC and ALSPC values. Analysis was repeated as a function of plan complexity for 250 non-stereotactic body radiotherapy (SBRT) VMAT patients at 3%/2mm and a threshold of 10% and for 75 SBRT VMAT patients at 2%/2 mm and a threshold of 50% with results plotted as a function of PTV volume. Regions of failure were dose-scaled on the planning CT data sets based on delivery results. RESULTS: The IMRT/VMAT TLSPC and ALSPC for gamma criteria of 3%/3 mm were 96.5% and 95.6% and for 3%/2 mm were 91.2% and 89.2%, respectively. Correlation with plan complexity for conventional fractionation VMAT was "low" for all sites with pelvis having the highest r value at -0.35. The equivalent SBRT PTV diameter ranged from 2.0 cm to 5.6 cm. Negative low correlation was found for 38 of 75 VMAT cases below ALuniv. CONCLUSIONS: The ALuniv and ALSPC are similar for 3%/2 mm. However, our 5% failure rate for ALuniv, may result in treatment start delays approximately 2 times/month, given 40 new cases/month. VMAT QA failure at stricter criteria did not correlate strongly with plan complexity. Site-specific action limits vary less than 3% from the average. SBRT QA results do not strongly correlate with target size over the range studied.

Monte Carlo Dose Calculation - A QA Method for SRT and SBRT Plans in Treating Multiple and Small Metastatic Lesions.

To provide accurate and fast 3-D dose verification for hypofractionated stereotactic radiotherapy (SRT/SBRT) of small and multi targets calculated with a Varian Eclipse treatment planning system (TPS) delivered on a Varian accelerator. Ten brain and lung hypofractionated SRT/SBRT linac-based and CyberKnife plans were generated by the Eclipse system for delivery on the accelerator with the Millenium-120 leaf multileaf collimator (MLC) and Multiplan for the CyberKnife machine. These clinical SRT/SBRT plans required accurate quality assurance measurements to obtain absolute point dose and 3-D dose distributions due to the low number of fractions and high fraction doses. For small-field and multi-target plans, the EGS4/MCSIM code was used to calculate the dose distribution. A 0.125 cc ion chamber, a 0.016 cc pin-point chamber and Kodak EDR2 film were used for the measurements and the results were compared with Monte Carlo (MC) calculations. The dosimetry for small-field and multi-target treatment plans is challenging due to the comparable range of secondary electrons and the field sizes defined by SRT/SBRT MLC segments. Our MC simulations can accurately reproduce the linac dose distributions (within 1%/1 mm) three dimensionally. For the clinical SRT/SBRT plans investigated in this work, the MC doses agreed within 3% with ion chamber measurements and within 2%/2 mm with film measurements. The doses calculated by the Eclipse AAA algorithm and Multiplan differed by no more than 5% from MC calculations for small (4-40 cc) Planning Target Volumes (PTVs). MC dose calculation provides accurate and fast 3-D dose verification for hypofractionated SRT for small and multi-target treatment plans generated by a Varian Eclipse TPS on a Varian accelerator and Multiplan treatment planning on the CyberKnife System.

A narrative review of pyrolysis and its role in ulcerative colitis.

Cell death is one of the inevitable life activities of cells during the growth and development of the body. Regulated cell death (RCD) is a type of cell death mode that can be regulated and depends on specific molecular mechanisms which play an essential role in various pathophysiological environments. Pyrolysis is a newly discovered method of programmed cell death mediated by members of the Gasdermin protein family which is characterized by the activation of inflammatory factors and the formation of cell membrane pores. The specific manifestations are the swelling of cells, the appearance of plasma membrane bullae and the release of cell contents after cell rupture. A cascade of inflammation occurs after cell death. Activation of inflammasomes activates the classic pyrolysis pathway depending on caspase-1 or the non-classical pyrolysis pathway depending on Caspase-4/5 /11 and the subsequent inflammation reaction, excessive immune response caused by microbial infection and danger signals can lead to a variety of inflammatory diseases. In the inflammatory response, large numbers of inflammasomes activate the substrate protein GSDMD. GSDMD mediates pyrolysis by forming pores in the plasma membrane and mitochondria. Many studies have shown that pyrolysis plays an essential role in inflammatory bowel disease and other inflammatory diseases. This article aims to elaborate on the molecular mechanisms of pyroptosis in ulcerative colitis (UC) pathogenesis and provide new therapeutic ideas for UC.

Pulsed low dose-rate radiotherapy: radiobiology and dosimetry.

Pulsed low dose-rate radiotherapy (PLDR) relies on two radiobiological findings, the hyper-radiosensitivity of tumor cells at small doses and the reduced normal tissue toxicity at low dose rates. This is achieved by delivering the daily radiation dose of 2 Gy in 10 sub-fractions (pulses) with a 3 min time interval, resulting in an effective low dose rate of 0.067 Gy min-1.In vitrocell studies andin vivoanimal experiments demonstrated the therapeutic potential of PLDR treatments and provided useful preclinical data. Various treatment optimization strategies and delivery techniques have been developed for PLDR on existing linear accelerators. Preliminary results from early clinical studies have shown favorable outcomes for various treatment sites especially for recurrent cancers. This paper reviews the experimental findings of PLDR and dosimetric requirements for PLDR treatment planning and delivery, and summarizes major clinical studies on PLDR cancer treatments.

Dosimetric evaluation of image-guided radiation therapy for prostate cancer.

The aim of this study was to investigate the dosimetric accuracy of imaged-guided radiation therapy for prostate patients using the in-room computed tomography (CT) target localization technique. A Siemens CT-on-rails system was used for patient setup and target localization for intensity-modulated radiation therapy (IMRT) of prostate cancer. Fifteen previously treated prostate patients were included in this retrospective study. CT-on-Rails scans were performed before and after the IMRT treatment under local IRB approval. A total of 15 original simulation CT scans and 98 post-treatment CT scans were contoured by the same oncologist to delineate the prostate target, bladder, and rectum. IMRT plans were generated on the original simulation CTs and the same MUs and leaf sequences were used to compute the dose distributions using post-treatment CTs. Varian Velocity deformable registration was used for the summation of the fractional doses and the cumulative doses were compared with the planned doses. For the 15 patients investigated, the mean isocenter shift was up to 4.0 mm in the left-right direction, 5.9 mm in the anterior-posterior direction and 5.6 mm in the superior-inferior direction due to interfractional organ motion. The mean rectal volume varied from 0.6 to 1.73 times and the mean bladder volume varied from 0.59 to 3.65 times between simulation and the end of treatment. The prescription dose to 95% of the PTV, Dp, was set to 76 Gy for all treatment plans. The dose to 95% of the clinical treatment volume (CTV), D95, was 74.0 to 77.6 Gy and the minimum CTV dose, Dmin, was 61.0 to 71.6 Gy, respectively, in the cumulative dose distributions. Detailed analyses showed that 7.1% of the treatment fractions had cold spots (< 85% of Dp) in the peripheral CTV, leading to Dmin < 64 Gy in the cumulative dose distributions for 4 patients. The rectal dose-volume constraints were violated in 35.7% of the treatment fractions while the bladder dose was much improved in 82.7% of the treatment fractions. The current IGRT procedure for patient setup and target localization using rigid-body registration based on contour/anatomy matching is effective for population-based PTV margins. For a small group of patients, specific PTV margins and/or real-time target monitoring/tracking will be necessary due to significant prostate deformation/rotation caused by inter- and intrafractional bladder and rectal volume variation.

[ABO gene subtypes and gene expression analysis in three cases of hematological malignancies patients].

Objective: To explore the application and discovery of genotyping, gene sequencing, and gene expression analysis in the determination of ABO blood group subtypes and antigen expression abnormalities in hematological malignancies patients. Methods: From June 2019 to May 2020, three clinical cases were found with forward and reverse ABO typing discrepancy or atypical serologic agglutination pattern in the laboratory and blood transfusion department of Hebei Yanda Ludaopei Hospital were selected. Sequence-specific primer PCR (PCR-SSP) and Sanger sequencing of ABO gene coding regions were performed to determine the ABO genotypes, and whole transcriptome sequencing was used to analyze ABO and FUT1 gene expression levels. Results: A 12-year-old female acute lymphoblastic leukemia patient was determined as O.01.02 and BA.04 sub-genotype, corresponding to the serological B(A) subtype, and her ABO gene expression was normal (354.80). A 41-year-old female acute myeloid leukemia patient was determined as A1.02 and B.01 genotype, corresponding to the serological A(1)B phenotype, and her ABO gene expression was significantly reduced (45.70). A 42-year-old male with myelodysplastic syndrome and myelofibrosis was determined as A1.02 and A2.05 sub-genotype, corresponding to the serological A(1) and A(2) phenotype, respectively, and his ABO expression was negative. FUT1 expression was in the normal range in all three cases. The clinical blood product infusion strategy was formulated according to the genotype and the corresponding immunological subtype, and no significant transfusion-related adverse reactions occurred. Conclusion: Blood group sub-genotypes or aberrant gene expression can lead to ambiguities in serological blood group determination in hematological malignancies patients. ABO genotyping and gene expression analysis can help in this scenario and escort blood product infusion safety.

Pelvic Reirradiation Utilizing Pulsed Low-dose Rate Radiation Therapy.

Pulsed low-dose rate radiation therapy has been shown to reduce normal tissue damage while decreasing DNA damage repair in tumor cells. In a cohort of patients treated with palliative or definitive pelvic reirradiation using pulsed low-dose rate radiation therapy, we observed substantial local control and low rates of toxicity.

Time and frequency to observe fiducial markers in MLC-modulated fields during prostate IMRT/VMAT beam delivery.

OBJECTIVE: This work investigates the time and frequency to observe fiducial markers in MLC-modulated fields during intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) beam delivery for real-time prostate localization. METHODS: Thirty seven prostate patients treated with IMRT or VMAT were included in this retrospective study. DRR images were generated for all MLC segments/control points using the TPS. The MLC leaf pattern of each control point was overlaid on the DRR, and the number of fiducials within the MLC opening was analyzed. EPID images of fiducials in a pelvic phantom were obtained to demonstrate the fiducial visibility during modulated beam delivery. RESULTS: Gold fiducials were visible on EPID images. The probability of seeing a number of fiducials within the MLC opening was analyzed. At least one fiducial was visible during 42 ± 2% and 52 ± 2% beam-on time for IMRT of the prostate with and without lymph nodes, and during 81 ± 4% and 80 ± 5% beam-on time for VMAT of the prostate with and without lymph nodes, respectively. The mean time interval to observe at least one fiducial was 8.4 ± 0.7 and 5.9 ± 0.5 s for IMRT of the prostate with and without the lymph nodes, respectively, and 1.6 ± 0.1 s for VMAT prostate patients. The estimated potential dosimetric uncertainty was 7% and 2% for IMRT and VMAT, respectively. CONCLUSIONS: Our results demonstrated that the time and frequency to observe fiducial markers in MLC-modulated fields during IMRT/VMAT beam delivery were adequate for real-time prostate localization. The beam's eye view fiducial positions could be used for intrafractional target monitoring and motion correction in prostate radiotherapy.

Radiodynamic therapy using 15-MV radiation combined with 5-aminolevulinic acid and carbamide peroxide for prostate cancer in vivo.

Photodynamic therapy has been clinically proven to be effective, but its effect is limited to relatively shallow tumors because of its use of visible light. Radiodynamic therapy (RDT) has therefore been investigated as a means to treat deep-seated tumors. In this study, the treatment effect of a novel form of RDT consisting of radiation combined with 5-aminolevulinic acid (5-ALA) and carbamide peroxide was investigated using a mouse model. Male nude mice were injected bilaterally and subcutaneously with human prostate cancer (PC-3) cells and randomized into 8 treatment groups, consisting of various combinations of 15-MV radiotherapy (RT), 5-ALA, and carbamide peroxide. The treatment effect of a single fraction of treatment was measured by calculating tumor growth delay, monitored using weekly MR scans. The ability of the drugs to be delivered to the tumors was qualitatively measured using 18 F-FDG PET/CT scans. RDT was shown to significantly delay the tumor growth for the mouse model and tumor cell line investigated in this work. Tumors treated with RDT showed a decrease in tumor growth of 24 ± 9% and 21 ± 8% at one and two weeks post-treatment, respectively. Peroxide and 5-ALA did not contribute significantly to tumor growth delay when administered alone or separately with RT. Blood perfusion was shown to be able to deliver agents to the tumors investigated in this work, although uptake of 18 F-FDG was shown to be non-uniform.

AAPM Task Group 329: Reference dose specification for dose calculations: Dose-to-water or dose-to-muscle?

Linac calibration is done in water, but patients are comprised primarily of soft tissue. Conceptually, and specified in NRG/RTOG trials, dose should be reported as dose-to-muscle to describe the dose to the patient. Historically, the dose-to-water of the linac calibration was often converted to dose-to-muscle for patient calculations through manual application of a 0.99 dose-to-water to dose-to-muscle correction factor, applied during the linac clinical reference calibration. However, many current treatment planning system (TPS) dose calculation algorithms approximately provide dose-to-muscle (tissue), making application of a manual scaling unnecessary. There is little guidance on when application of a scaling factor is appropriate, resulting in highly inconsistent application of this scaling by the community. In this report we provide guidance on the steps necessary to go from the linac absorbed dose-to-water calibration to dose-to-muscle in patient, for various commercial TPS algorithms. If the TPS does not account for the difference between dose-to-water and dose-to-muscle, then TPS reference dose scaling is warranted. We have tabulated the major vendors' TPS in terms of whether they approximate dose-to-muscle or calculate dose-to-water and recommend the correction factor required to report dose-to-muscle directly from the TPS algorithm. Physicists should use this report to determine the applicable correction required for specifying the reference dose in their TPS to achieve this goal and should remain attentive to possible changes to their dose calculation algorithm in the future.

Application of a directional palladium-103 brachytherapy device on a curved surface.

PURPOSE: The directional planar palladium-103 LDR device (CivaSheet TM ) may be used for intraoperative implantation at the interface between the tumor site and healthy tissue. Its dosimetric properties have been studied in the ideal case of application on a flat surface. The dosimetric impact of implanting this highly directional device on a curved surface that may be encountered in clinical treatments is analyzed. METHODS: CivaSheet is designed as an array of directional palladium-103 sources (CivaDots). From the postoperative computed tomography (CT) scans of three patients, the shape of each implanted CivaSheet was reconstructed. In order to obtain a realistic estimate of the distribution of curvatures, the mean radius of curvature at the location of each CivaDot was calculated. A Monte Carlo simulation (FLUKA) of a single CivaDot was designed, based upon published geometry and material specifications. Both the radial dose function analog and the two-dimensional anisotropy function analog for the CivaDot were validated in comparison with film measurements and benchmarked to published Monte Carlo data. A value for the dose-rate constant Λ = 0.587(19) cGy/h/U for a CivaDot source in water was calculated as well. Knowledge of the dose distribution in the vicinity of each source allowed the dose at any point around CivaSheets of different curvatures and orientations to be calculated. RESULTS: The local radius of curvature was found to be primarily between 2 and 8 cm in all three patient implants. On the unshielded side of an inward-facing curved CivaSheet implant of radius 2 cm, the calculated dose at 0.5 cm depth exceeded the prescribed dose by ∼20%, while on the shielded side the dose increased by a factor of two, thus compromising the shielding efficiency of the original design. On the unshielded side of an outward-facing curved implant, the dose at 0.5 cm depth decreased by ∼20%. CONCLUSIONS: When tumor bed curvature can be estimated from the preplanning CT scan, the results from this study provide quantitative guide for modifying the source strength to achieve the desired clinical results. In many intraoperative cases, however, accurate preplanning based on surface curvature may not be practical. In such situations, knowledge of the dosimetric impact of the surface curvature provides motivation for avoiding implantation geometries that can lead to either over/underdosing the target, or excess dose to healthy tissue.

Evaluation of the combined use of two different respiratory monitoring systems for 4D CT simulation and gated treatment.

PURPOSE: Two different respiratory monitoring systems (Varian's Real-Time Position Management (RPM) System and Siemens' ANZAI belt Respiratory Gating System) are compared in the context of respiratory signals and 4D CT images that are accordingly reconstructed. This study aims to evaluate the feasibility of combined use of RPM and ANZAI systems for 4DCT simulation and gated radiotherapy treatment, respectively. METHODS: The RPM infrared reflecting marker and the ANZAI belt pressure sensor were both placed on the patient's abdomen during 4DCT scans. The respiratory signal collected by the two systems was synchronized. Fifteen patients were enrolled for respiratory signal collection and analysis. The discrepancies between the RPM and ANZAI traces can be characterized by phase shift and shape distortion. To reveal the impact of the changes in respiratory signals on 4D images, two sets of 4D images based on the same patient's raw data were reconstructed using the RPM and ANZAI data for phase sorting, respectively. The volume of whole lung and the position of diaphragm apex were measured and compared for each respiratory phase. RESULTS: The mean phase shift was measured as 0.2 ± 0.1 s averaged over 15 patients. The shape of the breathing trace was found to be in disagreement. For all the patients, the ANZAI trace had a steeper falloff in exhalation than RPM. The inhalation curve, however, was matched for nine patients, steeper in ANZAI for five patients and steeper in RPM for one patient. For 4D image comparison, the difference in whole-lung volume was about -4% to +4% and the difference in diaphragm position was about -5 mm to +4 mm, compared in each individual phase and averaged over seven patients. CONCLUSIONS: Combined use of one system for 4D CT simulation and the other for gated treatment should be avoided as the resultant gating window would not fully match with each other due to the remarkable discrepancy in breathing traces acquired by the two different surrogate systems.

Local Control and Toxicity of External Beam Reirradiation With a Pulsed Low-dose-rate Technique.

PURPOSE: To evaluate the efficacy and toxicity of external beam reirradiation using a pulsed low-dose-rate (PLDR) technique. METHODS AND MATERIALS: We evaluated patients treated with PLDR reirradiation from 2009 to 2016 at a single institution. Toxicity was graded using the Common Terminology Criteria for Adverse Events, version 4.0, and local control was assessed using the Response Evaluation Criteria In Solid Tumors, version 1.1. On univariate analysis (UVA), the χ2 and Fisher exact tests were used to assess the toxicity outcomes. Competing risk analysis using cumulative incidence function estimates were used to assess local progression. RESULTS: A total of 39 patients were treated to 41 disease sites with PLDR reirradiation. These patients had a median follow-up time of 8.8 months (range 0.5-64.7). The targets were the thorax, abdomen, and pelvis, including 36 symptomatic sites. The median interval from the first radiation course and reirradiation was 26.2 months; the median dose of the first and second course of radiation was 50.4 Gy and 50 Gy, respectively. Five patients (13%) received concurrent systemic therapy. Of the 39 patients, 9 (23%) developed grade ≥2 acute toxicity, most commonly radiation dermatitis (5 of 9). None developed grade ≥4 acute or subacute toxicity. The only grade ≥2 late toxicity was late skin toxicity in 1 patient. On UVA, toxicity was not significantly associated with the dose of the first course of radiation or reirradiation, the interval to reirradiation, or the reirradiation site. Of the 41 disease sites treated with PLDR reirradiation, 32 had pre- and post-PLDR scans to evaluate for local control. The local progression rate was 16.5% at 6 months and 23.8% at 12 months and was not associated with the dose of reirradiation, the reirradiation site, or concurrent systemic therapy on UVA. Of the 36 symptomatic disease sites, 25 sites (69%) achieved a symptomatic response after PLDR, including 6 (17%) with complete symptomatic relief. CONCLUSION: Reirradiation with PLDR is effective and well-tolerated. The risk of late toxicity and the durability of local control were limited by the relatively short follow-up duration in the present cohort.

When and how to treat an IMRT patient on a second accelerator without replanning?

When a linear accelerator is unavailable for treatment, a clinical decision is imminent regarding whether a patient should be treated on a linear accelerator other than the machine the patient was scheduled on, or whether treatment should be postponed until the original Linac becomes available. This work investigates the feasibility of switching patients to different accelerators for intensity-modulated radiation therapy (IMRT). We have performed Monte Carlo simulations of photon beams from different Linac models and vendors. Prostate and head and neck (H&N) treatment plans for Siemens Primus, Primart, and Varian 21EX accelerators are studied in this work. Dose distributions for given plans are recalculated using different beam data with the same nominal energy from different Linacs. We have compared dose-volume histograms (DVHs) and the maximum, the minimum, and the mean doses to the target and critical structures because of switching accelerators. In the process of switching a treatment plan to a different accelerator, issues exist, including optimum penumbra compensation, dose distribution at the boundary of target and critical structures, and multileaf collimator (MLC) leaf-width effects, which need to be considered and verified with measurements. Our Monte Carlo simulation results confirm that, for the cases we tested, the dose received by 95% of the planning target volume differs by 0.2% to 1.5% between Siemens Primus and Varian 21EX Linacs. The discrepancy is within our clinical acceptance criteria of 3% for IMRT treatments. In making the final decision on whether to switch machines or not, the tumor control probabilities (TCPs) based on a linear-quadratic model are compared. Based on the analyses performed in this work, it is therapeutically more beneficial to switch a patient to a different machine than to postpone a treatment until the original machine is available, especially for fast-growing tumors such as H&N cancers.

Induction chemotherapy followed by concurrent chemoradiation and nimotuzumab for locoregionally advanced nasopharyngeal carcinoma: preliminary results from a phase II clinical trial.

Overexpression of epidermal growth factor receptor can be found in more than 80% of patients with locoregionally advanced nasopharyngeal carcinoma and is associated with shorter survival. In this work, we evaluated the feasibility of adding nimotuzumab to chemoradiation in locoregionally advanced nasopharyngeal carcinoma. Twenty-three patients with clinically staged T3-4 or any node-positive disease were enrolled. They were scheduled to receive one cycle of induction chemotherapy followed by intensity-modulated radiotherapy, weekly administration of nimotuzumab and concurrent chemotherapy. Results showed that all patients received a full course of radiotherapy, 19(82.6%)patients completed the scheduled neoadjuvant and concurrent chemotherapy, and 22(95.7%) patients received ≥6 weeks of nimotuzumab. During the period of concurrent chemoradiation and nimotuzumab, grade 3-4 toxicities occurred in 14(60.9%) patients: 8 (34.8%) had grade 3-4 oral mucositis, 6(26.1%) had grade 3 neutropenia, and 1(4.3%) had grade 3 dermatitis. No acne-like rash was observed. With a median follow-up of 24.1 months, the 2-year progression-free survival and overall survival were 83.5% and 95.0%, respectively. In conclusion, concurrent administration of chemoradiation and nimotuzumab was well-tolerated with good compliance. Preliminary clinical outcome data appear encouraging with favorable normal tissue toxicity results comparing with historical data of concurrent chemoradiation plus cetuximab.

Treatment of hepatic tumors by thermal versus mechanical effects of pulsed high intensity focused ultrasound in vivo.

The purpose of this study is to comparatively assess the thermal versus mechanical effects of pulsed high intensity focused ultrasound (HIFU) treatment on hepatic tumors in vivo. Forty-five rabbits with hepatic VX2 tumors were randomly separated into three groups (15 animals per group) before HIFU ablation. The total HIFU energy (in situ) of 1250 J was used for each tumor for three groups. In groups I and II, animals were treated with 1 MHz pulsed ultrasound at 1 Hz pulsed repetition frequency (PRF), 0.5 duty cycle (0.5 s on and 0.5 s off) and10 s duration for one spot sonication. For group II, in addition to HIFU treatment, microbubbles (SonoVue, Bracco, Milan, Italy) were injected via vein before sonication acting as a synergist. In group III, animals were treated with 1 MHz pulsed ultrasound at 10 Hz PRF, 0.1 duty cycle (0.1 s on and 0.9 s off) and 10 s duration for one sonication. The total treatment spots were calculated according to the tumor volume. Tumors were examined with contrast-enhanced computed tomography (CECT) immediately prior to and post HIFU treatment. Histopathologic assessment was performed 3 h after treatment. Our study showed that all animals tolerated the HIFU treatment well. Our data showed that mechanical HIFU could lead to controlled injury in rabbit hepatic tumors with different histological changes in comparison to thermal HIFU with or without microbubbles.