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1.
Phys Rev Lett ; 127(17): 171801, 2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34739288

RESUMO

Using a dataset of 6.32 fb^{-1} of e^{+}e^{-} annihilation data collected with the BESIII detector at center-of-mass energies between 4178 and 4226 MeV, we have measured the absolute branching fraction of the leptonic decay D_{s}^{+}→τ^{+}ν_{τ} via τ^{+}→e^{+}ν_{e}ν[over ¯]_{τ}, and find B_{D_{s}^{+}→τ^{+}ν_{τ}}=(5.27±0.10±0.12)×10^{-2}, where the first uncertainty is statistical and the second is systematic. The precision is improved by a factor of 2 compared to the previous best measurement. Combining with f_{D_{s}^{+}} from lattice quantum chromodynamics calculations or the |V_{cs}| from the CKMfitter group, we extract |V_{cs}|=0.978±0.009±0.012 and f_{D_{s}^{+}}=(251.1±2.4±3.0) MeV, respectively. Combining our result with the world averages of B_{D_{s}^{+}→τ^{+}ν_{τ}} and B_{D_{s}^{+}→µ^{+}ν_{µ}}, we obtain the ratio of the branching fractions B_{D_{s}^{+}→τ^{+}ν_{τ}}/B_{D_{s}^{+}→µ^{+}ν_{µ}}=9.72±0.37, which is consistent with the standard model prediction of lepton flavor universality.

2.
Oper Dent ; 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34757375

RESUMO

The aim of this study was to evaluate interfacial gap formation of CAD/CAM lithium disilicate inlay margins before and after thermomechanical loading. METHODS AND MATERIALS: Mesio-occlusal-distal cavities were prepared on 12 extracted mandibular molars. The gingival margin of one proximal box was elevated with resin modified glass ionomer (RMGI) by a height of 2 mm (Group E [elevation]), and the margin of the other side served as a control (Group NE [no elevation]). Lithium disilicate computer-aided design and computer-aided manufacturing (CAD/CAM) inlays were fabricated and bonded with a self-adhesive resin cement. An aging process was simulated on the specimens under thermomechanical cycling by using a chewing simulator. Marginal integration was evaluated under scanning electron miscroscopy (SEM) using epoxy resin replicas before and after cycling. Marginal areas were stained with silver nitrate solution, and the volumetric gap was measured at the bonded interfaces using microcomputed tomography (CT) before and after cycling. Statistical analyses were performed using paired t-tests, the Wilcoxon signed rank test, and the Mann-Whitney test (a<0.05). RESULTS: SEM showed marginal discontinuities in Group NE that increased after thermomechanical cycling. Micro-computed tomography exhibited three-dimensional dye-penetrating patterns at the interfaces before and after cycling. Interfacial disintegration was larger in Group NE before cycling (p<0.05). Thermomechanical cycling increased the gaps in both Groups NE and E (p<0.05). The gap increment from thermomechanical cycling was larger in Group NE (p<0.05). CONCLUSIONS: Thermomechanical cycling induced interfacial disintegration at the lithium disilicate CAD/CAM inlays, with deep proximal margins. Margin elevation with RMGI placement reduced the extent of the interfacial gap formation before and after the aging simulation.

3.
Phys Rev Lett ; 127(13): 131801, 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34623854

RESUMO

Using 2.93 fb^{-1} of e^{+}e^{-} collision data taken with the BESIII detector at a center-of-mass energy of 3.773 GeV, the observation of the D^{0}→K_{1}(1270)^{-}e^{+}ν_{e} semileptonic decay is presented. The statistical significance of the decay D^{0}→K_{1}(1270)^{-}e^{+}ν_{e} is greater than 10σ. The branching fraction of D^{0}→K_{1}(1270)^{-}e^{+}ν_{e} is measured to be (1.09±0.13_{-0.16}^{+0.09}±0.12)×10^{-3}. Here, the first uncertainty is statistical, the second is systematic, and the third originates from the assumed branching fraction of K_{1}(1270)^{-}→K^{-}π^{+}π^{-}. The fraction of longitudinal polarization in D^{0}→K_{1}(1270)^{-}e^{+}ν_{e} is determined for the first time to be 0.50±0.19_{stat}±0.08_{syst}.

4.
Phys Rev Lett ; 127(12): 121802, 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34597097

RESUMO

The absolute branching fraction of Λ→pµ^{-}ν[over ¯]_{µ} is reported for the first time based on an e^{+}e^{-} annihilation sample of 10×10^{9} J/ψ events collected with the BESIII detector at sqrt[s]=3.097 GeV. The branching fraction is determined to be B(Λ→pµ^{-}ν[over ¯]_{µ})=[1.48±0.21(stat)±0.08(syst)]×10^{-4}, which is improved by about 30% in precision over the previous indirect measurements. Combining this result with the world average of B(Λ→pe^{-}ν[over ¯]_{e}), we obtain the ratio {[Γ(Λ→pµ^{-}ν[over ¯]_{µ})]/[Γ(Λ→pe^{-}ν[over ¯]_{e})]} to be 0.178±0.028, which agrees with the standard model prediction assuming lepton flavor universality. The asymmetry of the branching fractions of Λ→pµ^{-}ν[over ¯]_{µ} and Λ[over ¯]→p[over ¯]µ^{+}ν_{µ} is also determined, and no evidence for CP violation is found.

6.
Int J Radiat Oncol Biol Phys ; 111(3S): e201, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34700901

RESUMO

PURPOSE/OBJECTIVE(S): The use of external beam accelerated partial breast irradiation (APBI) using a twice-per-day regimen has raised concerns about increase rates of late toxicities. We compared toxicity outcomes of external beam APBI using a once-per-day regimen and accelerated hypofractionated whole breast irradiation (AWBI) in patients with early-stage breast cancer. MATERIALS/METHODS: This was a single-institution, retrospective cohort study. Patients aged ≥50 years with pTisN0 or pT1N0 breast cancer who underwent breast-conserving surgery and adjuvant radiotherapy were included. APBI was delivered at 38.5 Gy in 10 fractions once daily using magnetic resonance imaging (MRI)-guided radiotherapy only to patients who were strictly "suitable", according to the ASTRO-APBI guidelines. AWBI was delivered at 40.5-43.2 Gy in 15 or 16 fractions with or without a boost. RESULTS: Between October 2015 and December 2018, 173 and 300 patients underwent APBI and AWBI, respectively. At a median follow-up of 34.9 months (range 7.1 to 55.4 months), the 3-year recurrence-free survival rates of the APBI and AWBI groups were both 99.2% (P = 0.63). Acute toxicities were less frequent in the APBI than AWBI group (grade 1: 95 [54.9%] vs. 233 [77.7%] patients; grade 2: 7 [4.0%] vs. 44 [14.7%] patients; no grade ≥3 toxicities were observed in either group, P < 0.001). Late toxicities were less common in the APBI than AWBI group (grade 1: 112 [64.7%] vs. 197 [65.7%] patients; grade 2: 9 [5.2%] vs. 64 [21.3%] patients; grade 3: 0 vs. 5 [1.7%] patients, P < 0.001). Multivariate analysis showed that APBI was significantly associated with fewer late toxicities of grade ≥2 compared with AWBI (odds ratio 4.17, P = 0.006). CONCLUSION: Once-per-day APBI using MRI-guided radiotherapy afforded excellent locoregional control and fewer toxicities compared with AWBI. This scheme could be an attractive alternative to AWBI in patients who meet the ASTRO-APBI guidelines.

7.
Int J Radiat Oncol Biol Phys ; 111(3S): e218, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34700938

RESUMO

PURPOSE/OBJECTIVE(S): CPAP is a novel method to avoid heart radiation exposure during radiation therapy, recently proposed as an alternative to the current standard-of-care deep inspiration breath-hold technique. In this study, the heart dose, inter- and intrafraction motions in CPAP-based treatment were investigated. MATERIALS/METHODS: A retrospective study on heart dose level and CPAP compliance included 237 left-sided breast cancer patients treated with CPAP-based VMAT in hypofractionation (with (n = 116) and without (n = 105) internal mammary node irradiation (IMNI)) between June 2020 and January 2021. During simulation, CT was obtained with free breathing (FB) and CPAP. For each treatment fraction, CBCT was acquired to confirm geometric accuracy within 3 mm tolerance. Two different datasets were used for reproducibility evaluations. Dataset 1: interfraction reproducibility was evaluated by measuring heart-to-PTV distance (MinHD), defined as the minimum distance between the line posteriorly tangential to the PTV and the heart, on 300 CBCT and 20 planning CT data of 20 women. Using dataset 1, heart-sparing effect was further explored by comparing dosimetric metrics of the whole heart and its substructures (e.g., atrium, ventricles, and vessels) between CPAP- and FB-based VMAT plans. Dataset 2: intrafraction reproducibility was evaluated in 20 women who were treated for different malignancies and underwent 4D CT with CPAP. RESULTS: Among 237 patients recruited, the CPAP compliance was 93% with a mean heart dose of 1.6 ± 0.7 Gy (no IMNI, 1.1 Gy; IMNI 2.0 Gy). The use of CPAP during treatment did not require additional time resource. The analysis of dataset 1 (i.e., total of 300 CBCT and 20 planning CT images) showed small variations of MinHD (0.6 ± 0.2 cm), demonstrating a reasonable agreement of the heart-to-PTV distance between the planning CT and CBCTs (MinHD difference < 0.2 cm, on average, for all patients). Compared with FB, the use of CPAP significantly reduced the mean heart dose (2.1 to 1.7 Gy), the mean dose to the left ventricle, the maximum dose to the left anterior descending artery, and the mean lung dose by 21%, 23%, 36%, and 23%, respectively. In dataset 2, the breast surface motion amplitude was 0.5 ± 0.5, 2.5 ± 2.0, and 1.8 ± 1.4 mm across the patients in the mediolateral, craniocaudal, and anteroposterior directions, respectively, and exceeded 5 mm for only two patients. CONCLUSION: To the best of our knowledge, this is the first and largest study to evaluate the heart-sparing capability and reproducibility of CPAP-based VMAT for left-sided breast cancer treatment. A large population study confirmed a reasonably low irradiation to the heart with CPAP. This heart-sparing effect can be consistent across treatment fractions as demonstrated in sub-centimeter reproducibility of the heart position. For most of the women, the intrafraction breast motion with CPAP was minimal.

8.
Int J Radiat Oncol Biol Phys ; 111(3S): e221, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34700945

RESUMO

PURPOSE/OBJECTIVE(S): Although radiation-induced cardiac toxicity is an important issue in breast radiation therapy (RT), the dose relationship between cardiac structures and its toxicity has not been fully elucidated, partially because many centers do not routinely administer intravenous (IV) contrast for breast RT, which preclude substructure delineation and detection of potential correlations. In this study, we attempted to generate the synthetic contrast-enhanced CT (CECTsyn) from the non-contrast CT (NCTreal) using deep convolutional neural network (DCNN) and to investigate whether CECTsyn can take a supportive role in case the studies for the cardiac toxicity induced by radiation is needed for the patient whose CECTreal cannot be obtained. MATERIALS/METHODS: For this study, 22 NCTreal-CECTreal cardiac scan-pairs have been prepared of which the volume size was ∼512 × 512 × 400 and the resolution was ∼0.75 × 0.75 × 1 mm3 on average. Of the 22 datasets, 13/2/7 were used for training, validation, and testing, respectively. After matching the structure of paired scans using the deformable image registration (DIR), the area near the heart was cropped and used for training the deep learning model. We adopted the modified 2D fully convolution DenseNet (FC-DenseNet) as our backbone and trained it in the conditional generative adversarial network (cGAN) framework. The similarity between CECTsyn and CECTreal was evaluated first, and all NCTreal,CECTsyn, and CECTreal were applied to pre-trained cardiac auto-segmentation models to obtain the substructures of the heart, which is used for dose assessments in each of them. Finally, dose evaluations were conducted on CECTsyn and CECTreal with the dose distributions which are from clinical treatment plans and the manually modified contours of cardiac substructures. RESULTS: Firstly, the peak signal-to-noise ratio (PSNR) and the structural similarity index measure (SSIM) between CECTsyn and CECTreal were 23.96 and 0.772, whereas those of NCTreal and CECTreal were 22.25and 0.748, respectively. Secondly, the results of applying the pre-trained cardiac auto-segmentation model were obtained, and the dice similarity coefficient (DSC) of CECTsyn was 0.762 on average which is superior to 0.267 of NCTreal and comparable to 0.843 of CECTreal. We could distinguish the L/R ventricles, L/R atriums, left anterior descending artery (LAD), and right coronary artery (RCA) clearly on CECTsyn. Finally, the dose differences between CECTsyn and CECTreal were on average 0.4/2.0 Gy in Dmean and Dmax, and 2.1/1.3/0.6/0.4/0.3/0.1/0.0% in V5 Gy, V10 Gy, V20 Gy, V30 Gy, V40 Gy, V50 Gy, and V60 Gy, respectively. CONCLUSION: DCNN model proposed here showed the feasibility of CECTsyn generation from NCTreal and potential for cardiac substructure delineation such as ventricles, atriums, LAD, and RCA on NCTreal for breast RT. Furthermore, it is shown that CECTsyn can play a supportive role when the studies for the radiation-induced cardiac toxicity is needed.

9.
Int J Radiat Oncol Biol Phys ; 111(3S): e224-e225, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34700954

RESUMO

PURPOSE/OBJECTIVE(S): Radiation-induced cardiac toxicity is an importantissue of breast RT. Although a relationship between mean heart dose and acute coronary event (ACE) risk was reported in previous study, the specific relationships between doses to cardiac structures or their sub-regions and subsequent toxicity have not been well defined. In this study, we studied the effect of radiation on specific heart segments on subsequent cardiac toxicity. MATERIALS/METHODS: From the 1294 patients with breast cancer where previously demonstrated a relationship between mean heart dose and ACE, 21 patients who developed HF following breast RT and 39 with ACE were identified after an independent review by cardiologists. The study included 21 and 39 controls for respective toxicity who were matched according to age, comorbidities, and physical activity. For each patient who received radiotherapy, substructures were manually drawn, and then dose-distribution parameters of heart and substructures (Mean, Maximum (Max) dose, Relative volume at least given dose from 5-50 Gy in 5 Gy increments) were collected from CT planning data. To specify most critical regions for developing ACE, analysis using High-dimensional Cox regression model (SNet) was performed to reveal the effect of radiation on specific heart segments on subsequent cardiac toxicity. RESULTS: In HF (n = 42) and ACE (n = 78) cohorts, characteristics between case and control were well matched. Mean time to develop heart failure, acute coronary events were 40.0 months and 42.2 months, respectively. In HF cohort, there was no significant difference not only in the mean heart dose (3.7 Gy vs 3.1 Gy, P = 0.652), but also in the mean left ventricle (LV) (5.0 Gy vs 4.1 Gy, P = 0.587), mean right ventricle (RV) (4.8 Gy vs 3.6 Gy, P = 0.473). On the other hand, in ACE cohort, there was significant difference in mean dose of heart (2.9 Gy vs 1.3 Gy, P = 0.015), left atrium (LA) (1.0 Gy vs 0.5 Gy, P = 0.008), LV (3.7 Gy vs 1.5 Gy, P = 0.028), left anterior descending artery (LAD) (6.6 Gy vs 2.4 Gy, P = 0.028) and right atrium (RA) (1.5 Gy vs 0.9 Gy, P = 0.025). In univariate analysis, mean dose of heart, LA, LV, LAD and RA was significant factors for acute coronary event free survival. ((Heart; P = 0.006, Hazard ratio (HR) 1.139, 95% Confidence Interval (CI) 1.035-1.253) (LA; P = 0.002, HR 1.735, 95% CI 1.209-2.490), (LV; P = 0.018, HR 1.079, 95% CI 1.012-1.150), (LAD; P = 0.031, HR 1.032, 95% CI 1.002-1.064), (RA; P = 0.008, HR = 1.307, 95% CI 1.068-1.598)). For predicting ACE risk for breast cancer patients, SNet model suggested nomogram based on mean and max LA dose, LAD V10, 15, 20, mean heart dose, mean RA dose and RV V35 in the order of higher predicted point variation. Based on this risk stratification model, event free survival significantly showed difference (P = 0.013). CONCLUSION: There was significant difference between cardiac substructure dose parameters in ACE cohort, but not in HF cohort. Further analysis using convolution neural network will be performed to specify most critical region to be spared.

10.
Int J Radiat Oncol Biol Phys ; 111(3S): e241-e242, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34700995

RESUMO

PURPOSE/OBJECTIVE(S): Radiation-induced sarcoma (RIS) is a rare secondary malignancy resulting from ionizing radiation-related treatment after a long latency period. Despite the unfavorable clinical outcomes, the genomic footprints of ionizing radiation in RIS development remain largely unknown. Hence, this study aimed to characterize RIS genomes and the genomic alterations in them. MATERIALS/METHODS: We performed whole-genome sequencing (WGS) of 11 cases of RIS matched with normal genomes to identify somatic alterations potentially associated with RIS development. RESULTS: The mutation abundance of RIS genomes including one hypermutated genome was variable. Cancer-related genes might show different types of genomic alterations. For instance, NF1, NF2, NOTCH1, NOTCH2, PIK3CA, RB1, and TP53 showed singleton somatic mutations; MYC, CDKN2A, RB1, and NF1 showed recurrent copy number alterations; and NF2, ARID1B, and RAD51B showed recurrent structural variations (SVs). The effects of non-homologous end joining on short insertions-deletions and SVs were substantial in RIS genomes, compared with in spontaneous osteosarcoma genomes, representing the genomic hallmark of RIS genomes. In addition, frequent chromothripsis and predisposing germline variants in DNA damage-repair pathways were identified. CONCLUSION: Taken together, WGS-scale characterization of RIS genomes may pave the way for advanced diagnostic and therapeutic strategies for RIS.

11.
Int J Radiat Oncol Biol Phys ; 111(3S): e266, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34701049

RESUMO

PURPOSE/OBJECTIVE(S): We present an interim analysis of toxicity and quality-of-life (QOL) from a randomized phase III trial of extreme hypofractionated versus standard hypofractionated proton therapy for low-risk prostate cancer. MATERIALS/METHODS: From 2011-2020, low-risk prostate cancer patients were randomized in a 1:2 fashion to standard fractionation (79.2 Gy [RBE] in 44 fractions, Arm A) versus extreme hypofractionation (38 Gy [RBE] in 5 fractions, Arm B) proton therapy. Patients were excluded if they had an American Urological Association Symptom Index (AUASI) > 17. Toxicity was defined according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 and adjusted for pre-treatment toxicities. Patients completed Expanded Prostate Cancer Index Composite + (EPIC), Short Form 12 (SF) and AUASI surveys at baseline and 3, 6, 12, 18, 24 and 36 months. RESULTS: Forty-six patients were included in Arm A and 84 patients in Arm B. Median follow-up was 50 months. The majority of patients were clinical T1c (89% Arm A, 84.5% Arm B, P = 0.86) and a PSA > 4-10 (80.4% Arm A, 78.6% Arm B, P = 1.00). For both groups, median AUASI was 5 (range 0-14). Four patients (1 Arm A, 3 Arm B) had died at the time of last follow-up, none related to their prostate cancer or treatment. Between the two arms, no significant differences were noted in acute treatment-related genitourinary (GU) or gastrointestinal (GI) toxicities: acute GU grade ≥ 2 (0% Arm A, 5% Arm B), GU grade ≥ 3 (0% each arm), GI grade ≥ 2 (0% Arm A, 2% Arm B), grade ≥ 3 (0% each arm). Similarly, no significant differences were noted in late treatment-related GU or GI toxicities: late GU grade ≥ 2 (26% Arm A, 33% Arm B), GU grade ≥ 3 (2% Arm A, 1% Arm B), GI grade ≥ 2 (13% Arm A, 19% Arm B), GI grade ≥ 3 (0% each arm). When analyzing QOL by arm and timepoints, only EPIC Overall scores at 36 months were clinically significantly different (> MID) between the two arms with Arm B having improved scores (+29.62 points, P = 0.02). Other QOL domains (EPIC Urinary, EPIC Bowel, AUASI) were not clinically significantly different between the two arms across timepoints. CONCLUSION: In a phase III randomized controlled trial comparing extreme hypofractionation to standard fractionation for the treatment of prostate cancer, no significant differences for treatment-related acute or late, grade ≥ 2 or ≥ 3, toxicity were found for GU or GI toxicities. Additionally, improved EPIC Overall scores at 36 months were found in patients treated with extreme hypofractionation. This trial was registered with Western IRB 20101536, and NCT01230866.

12.
Int J Radiat Oncol Biol Phys ; 111(3S): e295, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34701115

RESUMO

PURPOSE/OBJECTIVE(S): To report the analysis on the quality of life (QOL) and toxicity in intermediate-risk prostate cancer patients treated with or without androgen deprivation therapy (ADT) on PCG GU 003. MATERIALS/METHODS: Between 2012 and 2019, intermediate-risk prostate cancer patients were enrolled. Patients were randomized to receive moderately hypofractionated proton beam therapy (PBT) to 70 Gy relative biologic effectiveness (RBE) in 28 fractions to the prostate with or without 6 months of ADT. ADT was started 2 months prior to radiation and consisted of luteinizing hormone-releasing hormone (LHRH) agonists. Expanded Prostate Cancer Index Composite (EPIC), Short-Form 12, and the American Urological Association Symptom Index (AUASI) instruments were given at baseline, 3, 6, 12, 18, and 24 months after PBT. Toxicities were assessed according to Common Terminology Criteria for Adverse Events (Version 4). Clinically significant differences for EPIC domains were 6-9 points for urinary incontinence, 5-7 points for urinary irritative, 4-6 points for bowel, 10-12 points for sexual, and 4-6 points for hormonal. RESULTS: One hundred ten patients were randomized to PBT either with 6 months of ADT (n = 55) or without ADT (n = 55). Median follow-up was 32.4 months (range, 5.5-84.6). Patient and tumor characteristics were similar between arms with most patients being T1c (59.1%), Gleason 3+4 (62.7%) and PSA < 10 (79.1%). Baseline median AUASI was also similar (6 ADT vs 5 no ADT, P = 0.359). Acute and late grade 2+ genitourinary (GU) toxicity was similar between arms (acute 7.3% ADT vs 1.8% no ADT, P = 0.363; late 30.9% ADT vs 16.4% no ADT, P = 0.115). Acute and late grade 2+ gastrointestinal (GI) toxicity was similar between arms (acute 1.8% ADT vs 0% no ADT, P = 1; late 10.9% ADT vs 10.9% no ADT, P = 1). The only grade 3+ toxicities were in the ADT arm and consisted of 1 patient (1.8%) with an acute grade 3 GI and 1 patient (1.8%) with a late grade 3 GU toxicity. The ADT arm experienced worse overall QOL in the sexual (-16.1, P < 0.001) and hormonal (-6.3, P < 0.001) domains, with the largest time-specific hormonal differences at 3 (-13.8, P < 0.001) and 6 (-11.2, P < 0.001) months. However, there were no clinically significant differences 6 months after PBT. There were no clinically significant differences in AUASI, urinary incontinence, urinary irritative, or bowel domains. CONCLUSION: Low acute and late toxicity rates were seen in both arms of the trial. Omitting ADT resulted in clinically significant improvement in hormonal and sexual QOL, typically resolving within 12 months after PBT.

13.
Int J Radiat Oncol Biol Phys ; 111(3S): e300, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34701128

RESUMO

PURPOSE/OBJECTIVE(S): We aimed to evaluate the association between autoimmune disease (AID) and lymphoma incidence in the Korean population. We also aimed to compare the overall survival (OS) in patients with AID-associated lymphoma (AAL) with that in patients with lymphoma without AID. MATERIALS/METHODS: We used National Sample Cohort 2002-2015 provided by National Health Insurance Service. Among 1,011,638 patients, 994,496 were recruited for the final cohort: 130,987 patients (13.2%) in the AID group and 863,509 (86.8%) in control. Lymphoma was diagnosed in 1,162 patients and 322 patients with accompanying AID, irrespective of the time point of diagnosis, were defined as AAL. Of those, patients who experienced lymphoma development at least one year after AID diagnosis were defined as post-AID lymphoma (N = 155). RESULTS: The median follow-up duration was 13.7 years. AAL accounted for 0.03% of total and 27.7% of lymphoma cases. AID patients experienced more Epstein-Barr virus (0.02 vs. 0.01%, P = 0.027) or Helicobacter pylori infection (63.9 vs. 41.4%, P < 0.001) than the control group did. AID was associated with a 1.45-fold increased risk of lymphoma. The median time interval from AID to AAL was 10.9 months. The risk of lymphoma increased in the order of: psoriasis (adjusted odds ratio [AOR] 1.61), systemic lupus erythematosus (AOR 3.99), multiple sclerosis (AOR 4.52), and sarcoidosis (AOR 26.37). Sjogren syndrome was not related to lymphoma in this cohort. The 5-year OS in AAL was not different from that in lymphoma patients without AID (60.9 vs. 61.5%, P = 0.970). CONCLUSION: The association patterns in AAL in Korean population were different from those of Western countries. Further studies on lymphomatogenesis from distinct baseline characteristics (e.g., chronic infection status) would elucidate the difference based on race and ethnicity.

14.
Int J Radiat Oncol Biol Phys ; 111(3S): e32, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34701172

RESUMO

PURPOSE/OBJECTIVE(S): Noninvasive cardiac radioablation has been reported to be effective and relatively safe for ventricular tachycardia (VT) in preclinical and clinical studies. However, previous studies implementing cardiac radioablation set a 6-12 weeks of "blanking period" and focused on long-term effects rather than reporting the early changes. In this prospective trial, we focused on the early antiarrhythmic effects within one month after cardiac radioablation. Especially, we tried to seek the differences in response according to the cause of VT. MATERIALS/METHODS: From September 2019 to December 2020, 6 patients (3 ischemic VTs and 3 non-ischemic VTs) were included in this trial and treated with stereotactic body radiotherapy (SBRT) with a single fraction of 25 Gy for intractable VT. A synthesis of imaging studies, 12-lead ECG, and electrophysiological mapping were used to localize the treatment target. The internal target volume was delineated on either maximal intensity projection of 4D-CT or deep inspiration breath hold CT. A 24-hour Holter monitoring was performed for all patients one month before and after SBRT and except for one patient, it was performed from 24 hours before SBRT to 48 hours after SBRT to measure the early response after SBRT. RESULTS: The number of total ventricular beats decreased by 58% and 60% within 24 hours and 48 hours after SBRT, respectively. It further decreased to 29% of pre-SBRT number of total ventricular beats at one month after SBRT. The decrease of total ventricular beats could be attributed to the decrease of VT burden rather than that of premature ventricular contractions (PVCs) because the burden of VT decreased earlier and more dramatically than that of PVC. After cardiac radioablation, the duration of the longest VT run was shortened. This indicated that cardiac radioablation decreases the VT burden by shortening the durations of VTs. Notably, the cardiac radioablation was more effective for ischemic VTs than non-ischemic VTs in that the VT burden decreased more markedly after SBRT. The electrophysiologic characteristics of VT/PVC were changed after treatment. During one month after SBRT, there was no severe acute toxicity. CONCLUSION: In six patients with intractable VT, the noninvasive cardiac radioablation with a dose of 25 Gy was effective even in 1-month follow-up. The decrease of VT burden through shortening of VTs already began within 24 hours after the procedure and continued to decrease until one month after the radioablation. The treatment effect was more remarkable in ischemic than non-ischemic VT patients.

15.
Int J Radiat Oncol Biol Phys ; 111(3S): e471-e472, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34701533

RESUMO

PURPOSE/OBJECTIVE(S): Retrospective and prospective studies in patients with oligometastatic non-small-cell lung cancer (NSCLC) suggested clinical benefit after complete metastatic ablation (CMA). So far, no studies have addressed the toxicity and efficacy of CMA to oligometastatic lesions in patients that progressed during immune checkpoint inhibitors (ICIs) therapy. Here, we report results of a single arm- radiotherapy (RT) to oligometastatic lesions from our ongoing phase II trial (NCT02710253). MATERIALS/METHODS: This study enrolled patients that progressed within 6 months of ICI therapy and developed oligo-metastases. Treatment intervention allowed for any dose and fractions of RT per the treating physician to all metastatic sites, with irradiation for up to 6 sites. Primary endpoints of this study are time to new lesion development, and disease control rate (DCR) by RECIST 1.1. Secondary endpoints are toxicity, progression-free survival (PFS), overall survival (OS) and absolute lymphocyte counts (ALC). RESULTS: Of the 30 patients initially enrolled in this study, 26 patients (N = 21 NSCLC; N = 5 melanoma) were included in the analysis as they had completed imaging follow-up. A total of 64 lesions were irradiated with a mean of 2.5 lesions per patient. Most frequent location of irradiated was lung (n = 45), followed by adrenal (n = 7), liver (n = 4), bone (n = 4) and others (n = 4); 50% of patients received SBRT. At a median follow-up time of 23.0 months (range, 5.0-44.7 months), 12 patients had no new lesions, while 14 patients developed new lesions in lung (50%), bone (25%), brain (21%). Median time to new lesion development was 14.6 months. DCR was 77% (complete response 19%, partial response 19%, stable disease 38%); median PFS was 10.1 months and median OS was not reached. No toxicities greater than grade 2 was observed. Pre-RT ALC is an independent risk factor for time to new lesion development (P = 0.006, HR = 0.1, 95% CI, 0.02-0.51). Patients without new lesion development had significantly higher baseline ALC (P = 0.011) and more ALC after RT at 1 month (P = 0.025), 3 months (P = 0.006), 6 months (P = 0.002) and 12 months (P = 0.045) compared to patients with new lesions. Other factors including age, gender, SBRT, baseline tumor size, performance status and tumor histology did not affect the time to new lesion development. CONCLUSION: In patients with oligometastatic lesions that progressed on ICI, CMA may be a valid treatment option that generates clinical benefits. By eradicating gross sites of disease by converting area sites into in-situ vaccines, T cells are able to access microscopic metastasis. Larger randomized trials are indicated to further define the role of CMA for ICIs resistance.

16.
Int J Radiat Oncol Biol Phys ; 111(3S): e518-e519, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34701644

RESUMO

PURPOSE/OBJECTIVE(S): Biology-guided Radiotherapy (BgRT) is a new external beam radiotherapy delivery modality combining positron emission tomography-computed tomography (PET-CT) with a linear accelerator. Our research group has previously introduced the BgRT specific prospective process map for developing an initial clinical workflow and has performed the risk analysis for the BgRT process that will bring in a new treatment paradigm. However, due to a lack of experience and historical data, assigning an accurate value of each risk factor in traditional FMEA leads to difficulties for evaluators. Also, there are certain sub-processes where the differences in weights of risk factors needs to be considered. Therefore, in this study, we introduced the fuzzy FMEA to perform a comprehensive analysis of failure modes (FMs) of BgRT and overcome weaknesses of conventional FMEA. MATERIALS/METHODS: Five sub-processes unique to BgRT out of a total of 15 sub-processes were selected and relevant 84 FMs were identified. The evaluators used the fuzzy linguistic variables (very low, low, medium, high, and very high) to evaluate the importance of risk factors for assigning weights as well as the evaluation of each risk factor (occurrence, severity, and detectability) of each failure mode. Then, the fuzzy measure was used to calculate the weights of risk factors and the fuzzy integral method was used to fuse every value of risk factor of FMs to obtain the final fuzzy risk priority number value. RESULTS: Top 3 FMs are the machine down/emergency during beam delivery, failure to meet activity before PET pre-scan, and failure/delay of tracer delivery from a local vendor. The mitigation plans are discussed by team members including complete guidelines for the emergencies on the treatment machine, maintenance program of PET tracers by dedicated staffs, and staff training program for the BgRT procedure. Strong cooperation with a local PET tracer vendor and timely patient scheduling to allow multiple PET images at the treatment machine were also included in mitigation plans. CONCLUSION: The proposed fuzzy FMEA presents a more reasonable and effective method for assessing potential failures allowing fuzzy linguistic variables terms that are easier to use than numerical assignments to evaluate the FMs, especially with the new prototype machine for BgRT. The results have been shared with team members, and mitigation plans will be implemented.

17.
Int J Radiat Oncol Biol Phys ; 111(3S): e519, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34701647

RESUMO

PURPOSE/OBJECTIVE(S): MR image based HDR brachytherapy is a complex, time-constrained and resource-intensive procedure requiring significant coordination and cooperation of multi-departmental efforts. Failure modes and effects analysis (FMEA) is an effective risk evaluation tool for identifying all possible failure modes (FMs) that could potentially impact negatively on the patient's treatment. Given the complexity of the MR image based HDR brachytherapy clinical workflow, FMEA can play a critical role in improving quality measures for each task. However, assigning a value between 1 to 10 to each of risk factor in traditional FMEA is a subjective and challenging task for the relevant multi-disciplinary team and potentially can cause considerable discrepancy and inconsistency. In this study, we introduced fuzzy inference based FMEA to provide better understanding of FMs to improve the quality assurance program for an efficient workflow and improved patient safety. MATERIALS/METHODS: A total of four major sub-processes and forty-five FMs were identified from "applicator insertion" to "treatment delivery". The fuzzy inference rule-based model uses three inputs of risk factors (severity, occurrence, and detectability) and single output of fuzzy risk priority number (RPN) consisting of five fuzzy linguistic terms (very low, low, medium, high, and very high) of triangular membership functions. This rule-based model is generated based on a set of fuzzy if-then rules by decision makers that relate input to output variables. Then, the defuzzification method was used to obtain a fuzzy RPN value. RESULTS: The team identified top three FMs of traditional FMEA. These were incorrect insertion of applicators by wrong identification ultrasound track, applicator moves, and incorrect channel length. Different rankings were produced depending on the rules of decision maker in fuzzy inference FMEA. Top 3 FMs of fuzzy FMEA were identified as missed/not detecting errors during physics second check, wrong applicator reconstruction, and poor quality of MR image set. The differences between the two RPN rankings are due to rules of decision making considering the probability of detecting errors in later process and severity. CONCLUSION: This is the first report for fuzzy inference based FMEA on MRI based HDR brachytherapy. The fuzzy FMEA model exhibits desirable properties that help overcome the drawbacks of the traditional FMEA and RPN, especially when dealing with multi-disciplinary team practice where their priorities on FMs are different. The results have been shared with team members, and mitigation plans are to be implemented for enhancing quality of care and improving patient safety.

18.
Int J Radiat Oncol Biol Phys ; 111(3S): e592, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34701826

RESUMO

PURPOSE/OBJECTIVE(S): Patients with glioblastoma (GBM) that involve the ventricle are at higher risk of ventricle opening during surgery and potential ventricular tumor spread. We evaluated the role of whole ventricular radiotherapy (WVRT) during postoperative temozolomide-based chemoradiotherapy. MATERIALS/METHODS: A retrospective review of 382 patients with GBM who received surgical resection followed by temozolomide-based chemoradiotherapy between 2005 to 2019 at a single institution was conducted. Propensity score matching was performed to compensate the difference in characteristics between patients that did (WVRT(+); n = 59) or did not (WVRT(-); n = 323) receive WVRT. Local, outfield, intraventricular, and leptomeningeal failure rates were compared. RESULTS: All WVRT(+) patients had tumor ventricle involvement and ventricle opening during surgery. In the propensity matched cohort, WVRT(+) group exhibited a significantly lower 2-year intraventricular failure rate compared to the WVRT(-) group (2.1% vs. 11.8%; P = 0.045), but no difference in other treatment outcomes. Recursive partitioning analysis stratified patients at higher risk of intraventricular failure (tumor ventricle involvement, MGMT unmethylation, and ventricle opening) with a 2-year rate of 14.2%. WVRT reduced intraventricular failure rates only in high-risk patients (0% vs. 14.2%; P = 0.054) or those with MGMT-unmethylated GBM in the matched cohort (0% vs. 17.3%; P = 0.036). WVRT did not cause a significant decline in performance status but caused a decrease in post-treatment absolute lymphocyte count, although it was recovered to a similar level with that of the WVRT(-) group. CONCLUSION: WVRT reduced intraventricular failure rates in patients with tumor ventricle involvement and ventricle opening during surgery. Our results merit further prospective evaluation of WVRT in GBM. AUTHOR DISCLOSURE: K. Kim: None. J. Yoo: None. S. Kang: None. J. Chang: None. H. Yoon: None. C. Suh: None.

19.
Int J Radiat Oncol Biol Phys ; 111(3S): e614, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34701881

RESUMO

PURPOSE/OBJECTIVE(S): We aimed to investigate the distinct transcriptional landscape in the poor responders to concurrent chemoradiotherapy (CCRT) and to gain mechanistic insights on treatment resistance in cervical cancer. MATERIALS/METHODS: RNA sequencing was performed using archived pre-treatment tissue biopsies of patients with locally advanced cervical cancer treated with concurrent platinum-based CCRT. Transcriptome data of patients with no durable benefit (NDB; progression-free period < 3 years) and durable clinical benefit (DCB; progression-free period > 5 years) after were compared. NDB score was estimated for each patient using the differentially expressed genes between NDB and DCB patients. Three independent cohorts, including The Cancer Genome Atlas cervical cancer (TCGA-CESC) cohort, were utilized for validation of NDB score. Potential response to PD-1 blockade was estimated with Tumor Immune Dysfunction and Exclusion (TIDE) score and T-cell-inflamed gene expression profile (GEP). RESULTS: Patients with NDB exhibited a distinct transcriptional profile compared to those with DCB such as higher signatures of extracellular matrix organization and epithelial-to-mesenchymal transition. The fraction of cancer-associated fibroblasts (CAFs) within the tumor was significantly higher in NDB than DCB patients. Higher NDB score was significantly associated with poor survival in the TCGA-CESC cohort (n = 274; P = 0.015), but only in patients that received curative aim radiotherapy (P = 0.002) and not in patients who received other treatments (P = 0.57). The transcriptomic characteristics of patients with NDB were recapitulated in patients with high NDB score in TCGA-CESC. Patients with high NDB score displayed significantly higher TIDE prediction score and lower T-cell-inflamed GEP score compared to patients with low NDB scores. CONCLUSION: Cervical cancer patients with poor treatment outcome following CCRT exhibited a distinct gene signature that was able to predict treatment outcomes. For poor responders, immune checkpoint inhibitors may be less effective and CAF-targeting treatments may be a promising approach. AUTHOR DISCLOSURE: K. Kim: None. J. Chang: None. Y. Kim: None.

20.
Int J Radiat Oncol Biol Phys ; 111(3S): e616-e617, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34701885

RESUMO

PURPOSE/OBJECTIVE(S): Cervical cancer is mainly treated by surgery, radiotherapy and chemotherapy. However, there are also some patients with treatment failure, such as residual tumors, recurrence or metastasis within a short period of time after the initial treatment. Apatinib is a targeted drug for a small molecule vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase inhibitor. We aimed to assess the efficacy and safety of apatinib combined with capecitabine in patients with recurrent/metastatic and persistent cervical cancer after radiochemotherapy. MATERIALS/METHODS: In this phase Ⅱ, single-arm, prospective study done in Guizhou province in China, eligible patients were aged 18-70 years, had an ECOG performance status of 0 or 1, progressed after at least one line of radiochemotherapy for metastatic, recurrent or persistent cervical cancer, and had measurable lesions. Patients received capecitabine 2000mg/m2 divided into morning and evening every day and apatinib 250mg once daily. Treatment continued until disease progression, unacceptable toxicity, and withdrawal of consent. The primary endpoint was the objective response rate (ORR) assessed by RECIST version 1.1 and Progression-free survival (PFS). Disease control rate (DCR), overall survival (OS),1-year survival rate and safety were the second endpoints. RESULTS: Between August 2018 and May 2020, 28 patients were enrolled and received study treatment. The median age was 52(range, 34-67) years. The median previous treatment lines were 2 (range, 2-5). As of Jan 1, 2021, median follow-up was 10.18 months (range, 3.4-29). 12 (42.9%; 95%: CI 23.5-62.3) of 28 patients who had at least one post-baseline tumor assessment (efficacy evaluation population) achieved an objective response, including 3 (10.7%) complete response (CR), and 9 (32.1%) partial response (PR). The median duration of response was 1.57months(range,0.9-2.17). The DCR was 82.1% (95% CI: 67.3% -97.2%). Median progression-free survival (PFS) was 4.7 months (95% CI: 1.2-18.6). The one-year survival rate was 54.8%, and the longest administration time was 18.2 months.10 (35.7%) patients had grade ≥ 3 treatment-related adverse events (TRAEs). Grade ≥ 3 TRAEs occurring in ≥ 5% of patients were hypertension (7.1%), emesis (7.1%), myelosuppression (7.1%). Notably, one patient discontinued maintenance therapy after 13 months because of coronary artery stenosis which is a rare toxic side effect of apatinib. CONCLUSION: Apatinib combined with capecitabine showed promising antitumor activity and tolerable toxicities in patients with recurrent/metastatic and persistent cervical cancer after chemotherapy.

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