Addition of Metastasis-Directed Therapy to Intermittent Hormone Therapy for Oligometastatic Prostate Cancer: The EXTEND Phase 2 Randomized Clinical Trial.

Importance: Despite evidence demonstrating an overall survival benefit with up-front hormone therapy in addition to established synergy between hormone therapy and radiation, the addition of metastasis-directed therapy (MDT) to hormone therapy for oligometastatic prostate cancer, to date, has not been evaluated in a randomized clinical trial. Objective: To determine in men with oligometastatic prostate cancer whether the addition of MDT to intermittent hormone therapy improves oncologic outcomes and preserves time with eugonadal testosterone compared with intermittent hormone therapy alone. Design, Setting, Participants: The External Beam Radiation to Eliminate Nominal Metastatic Disease (EXTEND) trial is a phase 2, basket randomized clinical trial for multiple solid tumors testing the addition of MDT to standard-of-care systemic therapy. Men aged 18 years or older with oligometastatic prostate cancer who had 5 or fewer metastases and were treated with hormone therapy for 2 or more months were enrolled to the prostate intermittent hormone therapy basket at multicenter tertiary cancer centers from September 2018 to November 2020. The cutoff date for the primary analysis was January 7, 2022. Interventions: Patients were randomized 1:1 to MDT, consisting of definitive radiation therapy to all sites of disease and intermittent hormone therapy (combined therapy arm; n = 43) or to hormone therapy only (n = 44). A planned break in hormone therapy occurred 6 months after enrollment, after which hormone therapy was withheld until progression. Main Outcomes and Measures: The primary end point was disease progression, defined as death or radiographic, clinical, or biochemical progression. A key predefined secondary end point was eugonadal progression-free survival (PFS), defined as the time from achieving a eugonadal testosterone level (≥150 ng/dL; to convert to nanomoles per liter, multiply by 0.0347) until progression. Exploratory measures included quality of life and systemic immune evaluation using flow cytometry and T-cell receptor sequencing. Results: The study included 87 men (median age, 67 years [IQR, 63-72 years]). Median follow-up was 22.0 months (range, 11.6-39.2 months). Progression-free survival was improved in the combined therapy arm (median not reached) compared with the hormone therapy only arm (median, 15.8 months; 95% CI, 13.6-21.2 months) (hazard ratio, 0.25; 95% CI, 0.12-0.55; P < .001). Eugonadal PFS was also improved with MDT (median not reached) compared with the hormone therapy only (6.1 months; 95% CI, 3.7 months to not estimable) (hazard ratio, 0.32; 95% CI, 0.11-0.91; P = .03). Flow cytometry and T-cell receptor sequencing demonstrated increased markers of T-cell activation, proliferation, and clonal expansion limited to the combined therapy arm. Conclusions and Relevance: In this randomized clinical trial, PFS and eugonadal PFS were significantly improved with combination treatment compared with hormone treatment only in men with oligometastatic prostate cancer. Combination of MDT with intermittent hormone therapy may allow for excellent disease control while facilitating prolonged eugonadal testosterone intervals. Trial Registration: ClinicalTrials.gov Identifier: NCT03599765.

Discrete Element Modelling of Cold Crushing Tests Considering Various Interface Property Distributions in Ordinary Refractory Ceramics.

The microstructures and local properties of ordinary refractory ceramic materials are heterogeneous and play a role in the fracture behavior of ordinary refractory ceramic materials. It is important to consider them in numerical modeling. Herein, the discrete element (DE) method was applied to determine the influences of heterogeneity of ordinary refractory ceramic materials by applying statistically distributed interface properties (uniform, Weibull), as opposed to constant interface properties, among the elements. Uniaxial cold crushing tests were performed as a case study. A reasonable loading strain rate for receiving quasi-static loading conditions and computation efficiency was evaluated. The loading wall displacement was recorded to present the stress-strain curves of cold crushing tests. Furthermore, the effects of the interface property distributions on the load/displacement curve, fracture energy, cold crushing strength, and fracture events were investigated. The results reveal that the DE method is a promising method for visualizing and quantifying the post-peak fracture process and crack events in ordinary refractory ceramics. Different interface property distributions contribute to significant variances in the load/displacement curve shape and fracture pattern. The heterogeneity of ordinary refractory ceramics can be further determined by comparing the experimental curves and fracture propagation along with an inverse identification approach.

Adding customized electron energy beams to TrueBeam linear accelerators.

PURPOSE: To better meet clinical needs and facilitate optimal treatment planning, we added two new electron energy beams (7 and 11 MeV) to two Varian TrueBeam linacs. METHODS: We worked with the vendor to create two additional customized electron energies without hardware modifications. For each beam, we set the bending magnet current and then optimized other beam-specific parameters to achieve depths of 50% ionization (I50 ) of 2.9 cm for 7 MeV and 4.2 cm for the 11 MeV beam with the 15 × 15 cm2 cone at 100 cm source-to-surface distance (SSD) by using an ionization chamber profiler (ICP) with a double-wedge (DW) phantom. Beams were steered and balanced to optimize symmetry with the ICP. After all parameters were set, full commissioning was done including measuring beam profiles, percent depth doses (PDDs), output factors (OFs) at standard, and extended SSDs. Measured data were compared between the two linacs and against the values calculated by our RayStation treatment planning system (TPS) following Medical Physics Practice Guideline 5.a (MPPG 5.a) guidelines. RESULTS: The I50 values initially determined with the ICP/DW agreed with those from a PDD-scanned in-water phantom within 0.2 mm for the 7 and 11 MeV on both linacs. Comparison of the beam characteristics from the two linacs indicated that flatness and symmetry agreed within 0.4%, and point-by-point differences in PDD were within 0.01% ± 0.3% for the 7 MeV and 0.01% ± 0.3% for the 11 MeV. The OF ratios between the two linacs were 1.000 ± 0.007 for the 7 MeV and 1.004 ± 0.007 for the 11 MeV. Agreement between TPS-calculated outputs and measurements were -0.1% ± 1.0% for the 7 MeV and 0.2% ± 0.8% for the 11 MeV. All other parameters met the MPPG 5.a's 3%/3-mm criteria. CONCLUSION: We were able to add two new beam energies with no hardware modifications. Tuning of the new beams was facilitated by the ICP/DW system allowing us to have the procedures done in a few hours and achieve highly consistent results across two linacs. PACS numbers: 87.55.Qr, 87.56.Fc.

Comparison of the Efficacy of Two Elastic Bandages for Forearm Hematoma After Transradial Coronary Intervention.

Background: This study compares the efficacy of two elastic bandages in treating forearm hematoma after transradial coronary intervention. Methods: A total of 60 patients with moderate or severe forearm hematoma following transradial coronary intervention were enrolled in this study. They were randomly divided into two groups, as follows: an Idealast-haft elastic bandage group (the observation group) and a control group. The patients in the Idealast-haft elastic bandage group received compression bandaging with Idealast-haft elastic bandages and the patients in the control group received compression bandaging with Nylexorgrip elastic bandages. Observation indexes related to, for example, forearm pain, arterial pulsation, blistering, skin color, and hemostasis time were compared between the two groups. Results: The results revealed that the times taken for pain disappearance, arterial pulse recovery, blister disappearance, skin color recovery, and compression hemostasis were significantly shorter in the Idealast-haft elastic bandage group than in the control group, and the differences were statistically significant (P < 0.05). The hematoma range and the arm circumference at the severest part of the hematoma decreased faster in the observation group than in the control group, and the differences were statistically significant (P < 0.05). Conclusion: The Idealast-haft elastic bandage is more effective than the Nylexorgrip elastic bandage in patients with forearm hematoma following transradial coronary intervention and should therefore be used in such cases.

Overexpression of G3BP1 facilitates the progression of colon cancer by activating ß­catenin signaling.

Ras­GTPase­activating protein SH3 domain­binding protein 1 (G3BP1) has been reported to be of importance in the occurrence and development of colon cancer. However, the underlying mechanisms remain largely unknown. Therefore, the aim of the present study was to investigate the role of Wnt/ß­catenin signaling in G3BP1­mediated colon cancer progression. The expression of G3BP1 in colon tissues and cells was detected via reverse transcription­quantitative PCR, western blotting and immunohistochemistry. Gain­of­function assays were performed in colon cancer RKO cells, which have a relatively low expression of G3BP1, while loss­of­function assays were performed in SW620 colon cancer cells, which have a relatively high expression of G3BP1. Cell proliferation, apoptosis and tumorigenesis were assessed using Cell Counting Kit­8, flow cytometry and tumor­bearing mice assays, respectively. The results demonstrated that G3BP1 expression was significantly upregulated in colon cancer tissues and cells compared with healthy colon tissues and cells. It was found that high expression of G3BP1 was closely associated with the poor prognosis and advanced clinical process in patients with colon cancer. Overexpression of G3BP1 in RKO cells enhanced their proliferative ability and decreased their apoptosis tendency, while knockdown of G3BP1 inhibited SW620 cell proliferation and induced apoptosis. In addition, G3BP1 interacted with ß­catenin and upregulated its expression and nuclear accumulation. It was identified that ß­catenin knockdown abolished the effects of G3BP1 on the enhancement of cell proliferation in vitro and tumor formation in vivo, as well as the inhibition of cell apoptosis. In conclusion, the present study demonstrated that G3BP1 promoted the progression of colon cancer by activating ß­catenin signaling, which provided novel evidence for the role of G3BP1 in colon cancer.

Scutellarein inhibits the development of colon cancer via CDC4­mediated RAGE ubiquitination.

Scutellarein has been identified to serve an anti­tumor function in human colon cancer, but the underlying mechanisms remain largely unclear. The present study further investigated the effect and mechanism of scutellarein, extracted from wild chrysanthemum, in the progression of colon cancer. MTT, clone formation, flow cytometry and tumor­bearing mice assays were used to detect cell viability, clone formation, apoptosis and tumorigenesis, respectively. Western blot and quantitative PCR assays were performed for protein and mRNA expression detection. The results revealed that, compared with the control group, scutellarein treatment significantly inhibited the viability and induced the apoptosis of colon cancer cells (P<0.05), with significant decreases in receptor for advanced glycosylation end products (RAGE) protein expression and stability and an increase in RAGE ubiquitination (P<0.05). However, the effects of scutellarein exerted in cell apoptosis and viability were rescued by RAGE overexpression, and accelerated by RAGE knockdown. Additionally, it was observed that scutellarein treatment induced a significant increase in the expression of cell division control protein 4 (CDC4) compared with the control group (P<0.05), which was then verified to interact with RAGE protein and mediate its ubiquitination. Overexpression of CDC4 inhibited colon cancer cell viability and promoted the apoptosis of SW480 and T84 cells, whereas this function was weakened when RAGE was overexpressed. Furthermore, CDC4 downregulation significantly neutralized scutellarein functions in promoting cell apoptosis and inhibiting cell viability and tumorigenesis in colon cancer cells compared with the scutellarein group (P<0.05). In conclusion, the present study revealed that scutellarein inhibited the development of colon cancer through upregulating CDC4­mediated RAGE ubiquitination.

[Effect of electroacupuncture preconditioning combined with induced urination on urinary retention after milligan-morgan hemorrhoidectomy].

OBJECTIVE: To investigate the effect of electroacupuncture preconditioning combined with induced urination on urinary retention after milligan-morgan hemorrhoidectomy. METHODS: Eighty patients with mixed hemorrhoids were randomly divided into an electroacupuncture group and a routine group, 40 cases in each group. Anesthesia at Yaoshu (GV 2) was given in the two groups. In the electroacupuncture group, electroacupuncture at Zhongji (CV 3)，Guanyuan (CV 4)，Pangguangshu (BL 28) and Sanyinjiao (SP 6) was applied with tolerant intensity for 30 min before operation, 2 Hz/100 Hz in frequency. After operation, induced urination was given, namely hot compress of bladder area and sound of hearing water. In the routine group，induced urination was given after operation. The score of the first urination waiting time, the distension of lower abdomen on the evening of the postoperative, the first time urinary volume and incidence of urinary retention were compared between the two groups. RESULTS: The scores of the first urination waiting time after operation and distension of lower abdomen in the evening of the postoperative in the electroacupuncture group were lower than those in the routine group, the first time urinary volume was more than that in the routine group, and the incidence of urinary retention was lower than that in the routine group (5.0% (2/40) vs 22.5% (9/40), all P<0.05). CONCLUSION: Electroacupuncture preconditioning combined with induced urination can effectively prevent the incidence of urinary retention after milligan-morgan hemorrhoidectomy.

[Effect of electroacupuncture preconditioning with different frequencies on anal pain after milligan-morgan hemorrhoidectomy].

OBJECTIVE: To compare the effect of electroacupuncture preconditioning with different frequencies on anal pain after milligan-morgan hemorrhoidectomy. METHODS: A total of 120 patients with mixed hemorrhoids were randomly divided into an electroacupuncture group A (dilatational wave, 2 Hz/100 Hz in frequency), an electroacupuncture group B (continuous wave, 2 Hz in frequency) and an electroacupuncture group C (continuous wave, 100 Hz in frequency), 40 cases in each group. Electroacupuncture at Xialiao (BL 34) and Chengshan (BL 57) was applied with tolerant intensity for 30 min before operation in all groups. The number of additional anesthetic drugs in the 3 groups, the visual anal pain score (VAS) and limb activity score at 4, 12, and 24 h after operation, the maximum VAS score within 24 h after surgery and oral dose of aminophenol dihydrocodeine were compared. RESULTS: The number of additional anesthetic drugs in the electroacupuncture group A, the electroacupuncture group B and the electroacupuncture group C were 4, 5, 4 respectively, and there was not statistically significant (P>0.05). There was no significant difference in the anal pain VAS score and limb activity score at 4 h after operation among the 3 groups (P>0.05), at the 12 h after operation, the VAS scores and limb activity scores in the electroacupunctures group A and B were lower than those in the electroacupuncture group C (P<0.05), at 24 h after operation, the VAS score and limb activity score in the electroacupuncture group A were lower than those in the electroacupuncture group B and C (P<0.05), the maximum VAS score within 24 h and oral dose of aminophenol dihydrocodeine within 24 h after operation in the electroacupuncture group A were lower than those in the electroacupuncture group B and C (P<0.05). CONCLUSION: Different frequency electroacupuncture preconditioning has the effect of alleviating anal pain after milligan-morgan hemorrhoidectomy. The analgesic effect of electroacupuncture with different frequencies is different. The electroacupuncture analgesic effect of 2 Hz /100 Hz dilatational wave is better than 2 Hz and 100 Hz continuous waves.

Automatic detection of graticule isocenter and scale from kV and MV images.

PURPOSE: To automate the detection of isocenter and scale of the mechanical graticule on kilo-voltage (kV) or mega-voltage (MV) films or electronic portal imaging device (EPID) images. METHODS: We developed a robust image processing approach to automatically detect isocenter and scale of mechanical graticule from digitized kV or MV films and EPID images. After a series of preprocessing steps applied to the digital images, a combination of Hough transform and Radon transform was performed to detect the graticule axes and isocenter. The magnification of the graticule was automatically detected by solving an optimization problem using golden section search and parabolic interpolation algorithm. Tick marks of the graticule were then determined by extending from isocenter along the graticule axes with multiples of the magnification value. This approach was validated using 23 kV films, 26 MV films, and 91 EPID images in different anatomical sites (head-and-neck, thorax, and pelvis). Accuracy was measured by comparing computer detected results with manually selected results. RESULTS: The proposed approach was robust for kV and MV films of varying image quality. The isocenter was detected within 1 mm for 98% of the images. The exceptions were three kV films where the graticule was not actually visible. Of all images with correct isocenter detection, 99% had a magnification detection error less than 1% and tick mark detection error less than 1 mm, with the exception of 1 kV film (magnification error: 3.17%; tick mark error: 1.29 mm) and 1 MV film (magnification error: 0.45%; tick mark error: 1.11 mm). CONCLUSION: We developed an approach to robustly and automatically detect graticule isocenter and scale from two-dimensionla (2D) kV and MV films. This is a first step toward automated treatment planning based on 2D x-ray images.

Randomized Trial of Hypofractionated, Dose-Escalated, Intensity-Modulated Radiation Therapy (IMRT) Versus Conventionally Fractionated IMRT for Localized Prostate Cancer.

PURPOSE: Hypofractionated radiotherapy delivers larger daily doses of radiation and may increase the biologically effective dose delivered to the prostate. We conducted a randomized trial testing the hypothesis that dose-escalated, moderately hypofractionated intensity-modulated radiation therapy (HIMRT) improves prostate cancer control compared with conventionally fractionated IMRT (CIMRT) for men with localized prostate cancer. PATIENTS AND METHODS: Men were randomly assigned to 75.6 Gy in 1.8-Gy fractions delivered over 8.4 weeks (CIMRT) or 72 Gy in 2.4 Gy fractions delivered over 6 weeks (HIMRT, biologically equivalent to 85 Gy in 1.8-Gy fractions assuming prostate cancer α-to-ß ratio of 1.5). Failure was defined as prostate-specific antigen (PSA) failure (nadir plus 2 ng/mL) or initiation of salvage therapy. Modified Radiation Therapy Oncology Group criteria were used to grade late (≥ 90 days after completion of radiotherapy) GI and genitourinary toxicity. RESULTS: Most of the 206 men (72%) had cT1, Gleason score 6 or 7 (99%), and PSA level ≤ 10 ng/mL (90%) disease. Androgen deprivation therapy was received by 24%. With a median follow-up of 8.5 years, men treated with HIMRT experienced fewer treatment failures (n = 10) than men treated with CIMRT (n = 21; P = .036). The 8-year failure rate was 10.7% (95% CI, 5.8% to 19.1%) with HIMRT and 15.4% (95% CI, 9.1% to 25.4%) with CIMRT. There was no difference in overall survival ( P = .39). There was a nonsignificant increase in late grade 2 or 3 GI toxicity with HIMRT (8-year 5.0% v 12.6%; P = .08). However, GI toxicity was only 8.6% when rectal volume receiving 65 Gy of HIMRT was ≤ 15%. Late genitourinary toxicity was similar ( P = .84). There was no grade 4 toxicity. CONCLUSION: The results of this randomized trial demonstrate superior cancer control for men with localized prostate cancer who receive dose-escalated moderately hypofractionation radiotherapy while shortening treatment duration.

[Clinical observation of electroacupuncture combined with auricular point sticking therapy for anal pain of mixed hemorrhoid after external excision and internal ligation].

OBJECTIVE: On the basis of western medication, to investigate the effect of electroacupuncture (EA) combined with auricular point sticking therapy for anal pain of mixed hemorrhoid after external excision and internal ligation，so as to explore the method of improving its effect. METHODS: Ninety patients of mixed hemorrhoids who received external excision and internal ligation were randomly assigned into an EA group, an auricular point sticking group and a combined group, 30 cases in each one. All the treatment was applied 30 min before surgery. Electroacupuncture was used at Xialiao (BL 34) and Changqiang (GV 1) in the EA group, once a day. The auricular points were bilateral shenmen (TF4), pizhixia (AT4), jiaogan (AH6a) and gangmen (HX5) in the auricular point sticking group, pressing 3-6 times every day, once 3-5 min. EA and auricular point sticking therapy were applied in the combined group. When the visual analogue scale (VAS) score was above 6, aminophenol dihydrocodeine was applied in the three groups. The scores of anal pain VAS and limb activity at the 4th, 12th, 24th, 48th, 72th hours after operation were compared among the three groups, as well as the maximum scores of VAS in 24 hours (T24max VAS) of 1-3 days after operation, the total dose of aminophenol dihydrocodeine 72 h after operation. RESULTS: The VAS and limb activity scores at all the time points after operation, the T24max VAS on the 1st, 2nd and 3rd days after operation and the dose of aminophenol dihydrocodeine in the combined group were better than those in the EA and auricular point sticking groups (all P<0.05). The VAS and limb activity scores at 4, 12, 24 h after operation and T24max VAS on the 1st day after operation in the EA group were lower than those in the auricularpoint sticking group (all P<0.05). The VAS and limb activity scores at 48, 72 h after operation, and the T24max VAS on the 2nd and 3rd days in the auricular point sticking group were lower than those in the EA group (all P<0.05). CONCLUSION: EA combined with auricular point sticking therapy are better than simple EA and auricular point sticking therapy for anal pain of mixed hemorrhoid after external excision and internal ligation. The analgesic effect of EA is rapider, and the effect of auricular point sticking therapy is longer. The combination of the two methods own coordination effect.

Independent evaluation of the effectiveness of IsoCal in improving image center accuracy on Varian TrueBeam and Clinac machines.

Modern medical linear accelerators (linacs) are often equipped with image guidance systems that are capable of megavolt (MV), kilovolt (kV), planar, or volumetric imaging. On Varian TrueBeam linacs, the isocenter accuracies of the imaging systems are calibrated with a procedure named IsoCal. On Clinac series linacs from Varian, installation of IsoCal is optional and the effects of IsoCal on the imaging systems can be turned on or off after the IsoCal procedure is performed. In this study, we report on the effectiveness of IsoCal in improving the coincidence of the image centers with the radiation isocenter, using an independent Winston-Lutz (WL) method to locate the radiation isocenter. A ball-bearing phantom was imaged with 2D MV, 2D kV, and cone beam computed radiography systems on two TrueBeam and two Clinac machines. Using the same phantom, digital WL tests with 16 combinations of gantry and collimator angles were performed to locate the radiation isocenter. The offsets between the IsoCal-calibrated image centers and the WL radiation isocenter were found to be within 0.4 mm on the four linacs in this study. When IsoCal was turned off, the maximal offsets of the image centers were greater than 1.0 mm on the two Clinac machines. The method developed in this study can be used as a vendor-independent quality assurance tool to assess the isocentricity of the image centers and radiation central axes.

[Acupuncture combined with acupoint catgut embedding sequential therapy for mild and moderate ulcerative colitis].

OBJECTIVE: To observe the efficacy of acupuncture combined with acupoint catgut embedding sequential therapy and medication for mild and moderate ulcerative colitis. METHODS: One hundred and twenty patients were randomized into an acupuncture and acupoint catgut embedding sequential therapy group (a combination group) and a mesalazine group, 60 cases in each one. Fifty-seven cases in the combination group and 55 cases in the mesalazine group were included into analysis. In the combination group, acupuncture was applied at Tianshu (ST 25), Shangjuxu (ST 37), Quchi (LI 11) during the activity period, and acupoint catgut embedding was applied at Pishu (BL 20), Zusanli (ST 36), Guanyuan (CV 4) during the alleviate period. The patients in the mesalazine group were treated with mesalazine orally. The treatment was given for 12 weeks. The scores of TCM symptoms, colonoscopy, mucosa healing rate were compared before and after treatment in the two groups. The effects, adverse reactions and the recurrent rates during 1-year follow-up were observed. RESULTS: After treatment, the scores of TCM symptoms decreased in the two groups (both P<0.05), and the result in the combination group was better than that in the mesalazine group (P<0.05). The total effective rate in the combination group was 87.7% (50/57), which was better than 70.9% (39/55) in the mesalazine group (P<0.05). The colonoscopy scores decreased after treatment in the two groups (both P<0.05). There was no significant difference between the two groups on colonoscopy score and mucosal healing rate [50.9% (29/57) vs 34.5% (19/55), both P>0.05]. The recurrent rate in the combination group was 8.5% (4/47)，which was lower than 32.4% (11/34) in the mesalazine group (P<0.05). No severe adverse reaction was found during the treatment in the two groups. CONCLUSION: Acupuncture combined with acupoint catgut embedding sequential therapy can improve mild and moderate ulcerative colitis and reduce the recurrent rate.

Patient-reported Urinary, Bowel, and Sexual Function After Hypofractionated Intensity-modulated Radiation Therapy for Prostate Cancer: Results From a Randomized Trial.

OBJECTIVES: Hypofractionated prostate radiotherapy may increase biologically effective dose delivered while shortening treatment duration, but information on patient-reported urinary, bowel, and sexual function after dose-escalated hypofractionated radiotherapy is limited. We report patient-reported outcomes (PROs) from a randomized trial comparing hypofractionated and conventional prostate radiotherapy. METHODS: Men with localized prostate cancer were enrolled in a trial that randomized men to either conventionally fractionated intensity-modulated radiation therapy (CIMRT, 75.6 Gy in 1.8 Gy fractions) or to dose-escalated hypofractionated IMRT (HIMRT, 72 Gy in 2.4 Gy fractions). Questionnaires assessing urinary, bowel, and sexual function were completed pretreatment and at 2, 3, 4, and 5 years after treatment. RESULTS: Of 203 eligible patients, 185 were evaluable for PROs. A total of 173 completed the pretreatment questionnaire (82 CIMRT, 91 HIMRT) and 102 completed the 2-year questionnaire (46 CIMRT, 56 HIMRT). Patients who completed PROs were similar to those who did not complete PROs (all P>0.05). Patient characteristics, clinical characteristics, and baseline symptoms were well balanced between the treatment arms (all P>0.05). There was no difference in patient-reported bowel (urgency, control, frequency, or blood per rectum), urinary (dysuria, hematuria, nocturia, leakage), or sexual symptoms (erections firm enough for intercourse) between treatment arms at 2, 3, 4, and 5 years after treatment (all P>0.01). Concordance between physician-assessed toxicity and PROs varied across urinary and bowel domains. DISCUSSION: We did not detect an increase in patient-reported urinary, bowel, and sexual symptom burden after dose-escalated intensity-modulated prostate radiation therapy using a moderate hypofractionation regimen (72 Gy in 2.4 Gy fractions) compared with conventionally fractionated radiation.

On the selection of gantry and collimator angles for isocenter localization using Winston-Lutz tests.

In Winston-Lutz (WL) tests, the isocenter of a linear accelerator (linac) is determined as the intersection of radiation central axes (CAX) from multiple gantry, collimator, and couch angles. It is well known that the CAX can wobble due to mechanical imperfections of the linac. Previous studies suggested that the wobble varies with gantry and collimator angles. Therefore, the isocenter determined in the WL tests has a profound dependence on the gantry and collimator angles at which CAX are sampled. In this study, we evaluated the systematic and random errors in the iso-centers determined with different CAX sampling schemes. Digital WL tests were performed on six linacs. For each WL test, 63 CAX were sampled at nine gantry angles and seven collimator angles. Subsets of these data were used to simulate the effects of various CAX sampling schemes. An isocenter was calculated from each subset of CAX and compared against the reference isocenter, which was calculated from 48 opposing CAX. The differences between the calculated isocenters and the reference isocenters ranged from 0 to 0.8 mm. The differences diminished to less than 0.2 mm when 24 or more CAX were sampled. Isocenters determined with collimator 0° were vertically lower than those determined with collimator 90° and 270°. Isocenter localization errors in the longitudinal direction (along the axis of gantry rotation) showed a strong dependence on the collimator angle selected. The errors in all directions were significantly reduced when opposing collimator angles and opposing gantry angles were employed. The isocenter localization errors were less than 0.2 mm with the common CAX sampling scheme, which used four cardinal gantry angles and two opposing collimator angles. Reproducibility stud-ies on one linac showed that the mean and maximum variations of CAX during the WL tests were 0.053 mm and 0.30 mm, respectively. The maximal variation in the resulting isocenters was 0.068 mm if 48 CAX were used, or 0.13 mm if four CAX were used. Quantitative results from this study are useful for understanding and minimizing the isocenter uncertainty in WL tests.

[Clinical observation on anal pendant expansion after PPH of mixed hemorrhoid treated with acupuncture at Xialiao (BL 34) and Changqiang (GV 1)].

OBJECTIVE: To compare the difference in the clinical efficacy on anal pendant expansion after PPH (procedure for prolapse and hemorrhoids) of mixed hemorrhoid between acupuncture at Xialiao (BL 34) and Chang-qiang (GV 1) and oral administration of diosmin. METHODS: Sixty cases of mixed hemorrhoids after PPH were randomized into an observation group and a control group, 30 cases in each one. In the observation group, since the 1st day, acupuncture had been applied to Xialiao (BL 34) and Changqiang (GV 1). The needles were retained for 30 min after qi arrival, and the treatment was given once a day, totally for 7 days. In the control group, diosmin tablets had been prescribed for oral administration since the 1st day, 0.9 g each time, twice a day, totally for 7 days. The degree, persistent time and the pain score of anal pendant expansion were compared on the 1st, 2nd, 3rd and 7th days after PPH between the two groups and the efficacy was evaluated. RESULTS: On the 1st day after PPH, the diffe-rences in the scores of the degree and persistent time of anal pendant expansion were not significant statistically between the two groups (all P>0.05), but the pain score in the observation group was lower than that in the control group (P<0.05) and lower than that before treatment (P<0.05). On the 2nd, 3rd and 7th days after PPH, the degree and persistent time of anal pendant expansion and pain score in the two groups were all lower than those before treatment (all P<0.05). The results in the observation group were better than those in the control group (all P<0.05). At the end of treatment (on the 7th day after PPH), the total effective rate in the observation group was higher than that in the control group[90.0% (27/30) vs 83.3% (25/30),P<0.05]. CONCLUSIONS: Acupuncture at Xialiao (BL 34) and Changqiang (GV 1) achieves the superior efficacy on anal pendant expansion after PPH of mixed hemorrhoids as compared with diosmin tablets.

Evaluation of the MIM Symphony treatment planning system for low-dose-rate- prostate brachytherapy.

MIM Symphony is a recently introduced low-dose-rate prostate brachytherapy treatment planning system (TPS). We evaluated the dosimetric and planning accuracy of this new TPS compared to the universally used VariSeed TPS. For dosimetric evaluation of the MIM Symphony version 5.4 TPS, we compared dose calculations from the MIM Symphony TPS with the formalism recommended by the American Association of Physicists in Medicine Task Group 43 report (TG-43) and those generated by the VariSeed version 8.0 TPS for iodine-125 (I-125; Models 6711 and IAI-125A), palladium-103 (Pd-103; Model 200), and cesium-131 (Cs-131; Model Cs-1). Validation was performed for both line source and point source approximations. As part of the treatment planning validation, first a QA phantom (CIRS Brachytherapy QA Phantom Model 045 SN#D7210-3) containing three ellipsoid objects with certified volumes was scanned in order to check the volume accuracy of the contoured structures in MIM Symphony. Then the DICOM data containing 100 patient plans from the VariSeed TPS were imported into the MIM Symphony TPS. The 100 plans included 25 each of I-125 pre-implant plans, Pd-103 pre-implant plans, I-125 Day 30 plans (i.e., from 1 month after implantation), and Pd-103 Day 30 plans. The dosimetric parameters (including prostate volume, prostate D90 values, and rectum V100 values) of the 100 plans were calculated independently on the two TPSs. Other TPS tests that were done included verification of source input and geometrical accuracy, data transfer between different planning systems, text printout, 2D dose plots, DVH printout, and template grid accuracy. According to the line source formalism, the dosimetric results between the MIM Symphony TPS and TG-43 were within 0.5% (0.02 Gy) for r > 1 cm. In the line source approximation validation, MIM Symphony TPS values agreed with VariSeed TPS values to within 0.5% (0.09 Gy) for r > 1 cm. Similarly, in point source approximation validation, the MIM Symphony values agreed to within 1% of the TG-43 and VariSeed values for r > 1 cm. The volume calculations obtained from the MIM Symphony TPS for the CIRS Brachytherapy QA Phantom were within 1% of the actual volume of the phantom. For the clinical cases, the volume and dosimetric parameter calculations for the prostate and rectum did not differ substantially between the pre-implant and Day 30 plans. Overall, our investigations showed negligible differences in dosimetry calculations and planning parameters between the two TPSs. The tests done to check the performance of the MIM Symphony TPS, such as the library data, data transfer, isodose and DVH printout, were found to be satisfactory. On the basis of these results, we conclude that the MIM Symphony TPS can be used as an alternative to the VariSeed TPS for low-dose-rate prostate brachytherapy.

Evaluation of IsoCal geometric calibration system for Varian linacs equipped with on-board imager and electronic portal imaging device imaging systems.

The purpose of this study is to evaluate the accuracy and reproducibility of the IsoCal geometric calibration system for kilovoltage (kV) and megavoltage (MV) imagers on Varian C-series linear accelerators (linacs). IsoCal calibration starts by imaging a phantom and collimator plate using MV images with different collimator angles, as well as MV and kV images at different gantry angles. The software then identifies objects on the collimator plate and in the phantom to determine the location of the treatment isocenter and its relation to the MV and kV imager centers. It calculates offsets between the positions of the imaging panels and the treatment isocenter as a function of gantry angle and writes a correction file that can be applied to MV and kV systems to correct for those offsets in the position of the panels. We performed IsoCal calibration three times on each of five Varian C-series linacs, each time with an independent setup. We then compared the IsoCal calibrations with a simplified Winston-Lutz (WL)-based system and with a Varian cubic phantom (VC)-based system. The maximum IsoCal corrections ranged from 0.7 mm to 1.5 mm for MV and 0.9 mm to 1.8 mm for kV imagers across the five linacs. The variations in the three calibrations for each linac were less than 0.2 mm. Without IsoCal correction, the WL results showed discrepancies between the treatment isocenter and the imager center of 0.9 mm to 1.6 mm (for the MV imager) and 0.5 mm to 1.1 mm (for the kV imager); with IsoCal corrections applied, the differences were reduced to 0.2 mm to 0.6 mm (MV) and 0.3 mm to 0.6 mm (kV) across the five linacs. The VC system was not as precise as the WL system, but showed similar results, with discrepancies of less than 1.0 mm when the IsoCal corrections were applied. We conclude that IsoCal is an accurate and consistent method for calibration and periodic quality assurance of MV and kV imaging systems.

Risk of late toxicity in men receiving dose-escalated hypofractionated intensity modulated prostate radiation therapy: results from a randomized trial.

OBJECTIVE: To report late toxicity outcomes from a randomized trial comparing conventional and hypofractionated prostate radiation therapy and to identify dosimetric and clinical parameters associated with late toxicity after hypofractionated treatment. METHODS AND MATERIALS: Men with localized prostate cancer were enrolled in a trial that randomized men to either conventionally fractionated intensity modulated radiation therapy (CIMRT, 75.6 Gy in 1.8-Gy fractions) or to dose-escalated hypofractionated IMRT (HIMRT, 72 Gy in 2.4-Gy fractions). Late (≥90 days after completion of radiation therapy) genitourinary (GU) and gastrointestinal (GI) toxicity were prospectively evaluated and scored according to modified Radiation Therapy Oncology Group criteria. RESULTS: 101 men received CIMRT and 102 men received HIMRT. The median age was 68, and the median follow-up time was 6.0 years. Twenty-eight percent had low-risk, 71% had intermediate-risk, and 1% had high-risk disease. There was no difference in late GU toxicity in men treated with CIMRT and HIMRT. The actuarial 5-year grade ≥2 GU toxicity was 16.5% after CIMRT and 15.8% after HIMRT (P=.97). There was a nonsignificant numeric increase in late GI toxicity in men treated with HIMRT compared with men treated with CIMRT. The actuarial 5-year grade ≥2 GI toxicity was 5.1% after CIMRT and 10.0% after HIMRT (P=.11). In men receiving HIMRT, the proportion of rectum receiving 36.9 Gy, 46.2 Gy, 64.6 Gy, and 73.9 Gy was associated with the development of late GI toxicity (P<.05). The 5-year actuarial grade ≥2 GI toxicity was 27.3% in men with R64.6Gy ≥ 20% but only 6.0% in men with R64.6Gy < 20% (P=.016). CONCLUSIONS: Dose-escalated IMRT using a moderate hypofractionation regimen (72 Gy in 2.4-Gy fractions) can be delivered safely with limited grade 2 or 3 late toxicity. Minimizing the proportion of rectum that receives moderate and high dose decreases the risk of late rectal toxicity after this hypofractionation regimen.

Quantification of beam complexity in intensity-modulated radiation therapy treatment plans.

PURPOSE: Excessive complexity in intensity-modulated radiation therapy (IMRT) plans increases the dose uncertainty, prolongs the treatment time, and increases the susceptibility to changes in patient or target geometry. To date, the tools for quantitative assessment of IMRT beam complexity are still lacking. In this study, The authors have sought to develop metrics to characterize different aspects of beam complexity and investigate the beam complexity for IMRT plans of different disease sites. METHODS: The authors evaluated the beam complexity scores for 65 step-and-shoot IMRT plans from three sites (prostate, head and neck, and spine) and 26 volumetric-modulated arc therapy (VMAT) plans for the prostate. On the basis of the beam apertures and monitor unit weights of all segments, the authors calculated the mean aperture area, extent of aperture shape irregularity, and degree of beam modulation for each beam. Then the beam complexity values were averaged to obtain the complexity metrics of the IMRT plans. The authors studied the correlation between the beam complexity metrics and the quality assurance (QA) results. Finally, the effects of treatment planning parameters on beam complexity were studied. RESULTS: The beam complexity scores were not uniform among the prostate IMRT beams from different gantry angles. The lateral beams had larger monitor units and smaller shape irregularity, while the anterior-posterior beams had larger modulation values. On average, the prostate IMRT plans had the smallest aperture irregularity, beam modulation, and normalized monitor units; the head and neck IMRT plans had large beam irregularity and beam modulation; and the spine stereotactic radiation therapy plans often had small beam apertures, which may have been associated with the relatively large discrepancies between planned and QA measured doses. There were weak correlations between the beam complexity scores and the measured dose errors. The prostate VMAT beams showed greater complexity than the prostate step-and-shoot IMRT beams. In the treatment planning process, the beam complexity increased as the minimum segment area decreased and as the number of optimization iterations and the maximum number of segments increased. CONCLUSIONS: The proposed metrics were effective in characterizing the beam complexity of different disease sites and for different treatment modalities. Efforts should be made to reduce the unnecessary complexity of IMRT beams to minimize the radiation dose uncertainties.