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Purpose: The combination of surface-guided radiation therapy (SGRT) and image-guided radiation therapy (IGRT) can provide complementary information of patient positioning throughout treatments. The ExacTrac Dynamic (EXTD) system is a combined SGRT and IGRT system that can provide real-time motion detection via optical surface and thermal tracking during treatment delivery, with stereoscopic x-ray for positional verification. The purpose of this study was to examine the performance of EXTD for intrafractional motion monitoring using real clinical cases. Methods and Materials: Treatment log files exported from EXTD for 40 patients with 335 fractions were retrospectively analyzed. Frequency of beam-hold triggered during treatments were recorded, with the comparison of shifts detected by optical surface tracking (EXTD_Thml) and x-ray verification (EXTD_Xray). Results: Among the 335 fractions, automatic beam-holds were triggered 41 times, followed by x-ray positional verification with internal anatomy. The difference of shifts detected by EXTD_Thml and EXTD_Xray were less than 1 mm and 1° in translational and rotational directions, respectively. After x-ray verification, none of them required the application of positional correction. Conclusions: The availability of x-ray imaging with optical surface tracking in EXTD is essential to verify whether geometric shifts are required to correct patient position. Considering the ability of continuous monitoring of patient positions with optical surface tracking and internal imaging, EXTD is an effective tool for intrafractional motion monitoring during radiation therapy.
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BACKGROUND: Although contrast-enhanced magnetic resonance imaging (MRI) detects early-stage nasopharyngeal carcinoma (NPC) not detected by endoscopic-guided biopsy (EGB), a short contrast-free screening MRI would be desirable for NPC screening programs. This study evaluated a screening MRI in a plasma Epstein-Barr virus (EBV)-DNA NPC screening program. METHODS: EBV-DNA-screen-positive patients underwent endoscopy, and endoscopy-positive patients underwent EGB. EGB was negative if the biopsy was negative or was not performed. Patients also underwent a screening MRI. Diagnostic performance was based on histologic confirmation of NPC in the initial study or during a follow-up period of at least 2 years. RESULTS: The study prospectively recruited 354 patients for MRI and endoscopy; 40/354 (11.3%) endoscopy-positive patients underwent EGB. Eighteen had NPC (5.1%), and 336 without NPC (94.9%) were followed up for a median of 44.8 months. MRI detected additional NPCs in 3/18 (16.7%) endoscopy-negative and 2/18 (11.1%) EGB-negative patients (stage I/II, n = 4; stage III, n = 1). None of the 24 EGB-negative patients who were MRI-negative had NPC. MRI missed NPC in 2/18 (11.1%), one of which was also endoscopy-negative. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of MRI, endoscopy, and EGB were 88.9%, 91.1%, 34.8%, 99.4%, and 91.0%; 77.8%, 92.3%, 35.0%, 98.7%, and 91.5%; and 66.7%, 92.3%, 31.6%, 98.1%, and 91.0%, respectively. CONCLUSION: A quick contrast-free screening MRI complements endoscopy in NPC screening programs. In EBV-screen-positive patients, MRI enables early detection of NPC that is endoscopically occult or negative on EGB and increases confidence that NPC has not been missed.
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Detección Precoz del Cáncer , Infecciones por Virus de Epstein-Barr , Herpesvirus Humano 4 , Imagen por Resonancia Magnética , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Neoplasias Nasofaríngeas/virología , Neoplasias Nasofaríngeas/diagnóstico por imagen , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/patología , Masculino , Persona de Mediana Edad , Femenino , Imagen por Resonancia Magnética/métodos , Detección Precoz del Cáncer/métodos , Adulto , Herpesvirus Humano 4/aislamiento & purificación , Carcinoma Nasofaríngeo/virología , Carcinoma Nasofaríngeo/diagnóstico por imagen , Carcinoma Nasofaríngeo/diagnóstico , Carcinoma Nasofaríngeo/patología , Estudios Prospectivos , Anciano , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/diagnóstico , ADN Viral/sangre , Carcinoma/diagnóstico por imagen , Carcinoma/virología , Carcinoma/diagnóstico , Carcinoma/patología , Sensibilidad y Especificidad , Endoscopía/métodos , Estadificación de Neoplasias , Tamizaje Masivo/métodos , Medios de Contraste/administración & dosificaciónRESUMEN
Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) is endemic to parts of Asia and overexpression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1α are common in NPC. Anti-vascular agents have known clinical activity in patients with recurrent/ metastatic NPC and in this study, we investigated the anti-tumor effect of BI 836880, a humanized bispecific nanobody against VEGF and angiopoietin-2 (Ang2), in preclinical models of EBV-positive and EBV-negative NPC. The efficacy of BI 836880 was also compared with bevacizumab, a recombinant humanized monoclonal antibody against VEGF. We found that BI 836880 could exert growth-inhibitory effect on endothelial cells (HUVEC-C) and the EBV-negative NPC cell line (HK1), but to a lesser extent in the EBV-positive NPC cell lines, C17C and C666-1. In patients-derived xenograft (PDX) models of NPC - Xeno-2117 and Xeno-666, BI 836880 could suppress tumor growth and Ki67, as well as induce tumor necrosis and reduce microvessel density. Moreover, treatment with BI 836880 increased the level of macrophage infiltration in both PDX tumor models of NPC, suggesting that BI 836880 may exert immunomodulatory effect on the NPC immune microenvironment. When compared with bevacizumab, BI 836880 appeared to show at least comparable activity as bevacizumab in terms of its anti-proliferative and anti-angiogenic effects. This study showed that BI 836880 has anti-proliferative, anti-angiogenic and possibly immunomodulatory effect in clinical models of NPC, therefore the dual targeting of VEGF and Ang2 signaling in NPC should be further investigated.
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BACKGROUND: The meta-analysis of chemotherapy for nasopharynx carcinoma (MAC-NPC) collaborative group previously showed that the addition of adjuvant chemotherapy to concomitant chemoradiotherapy had the highest survival benefit of the studied treatment regimens in nasopharyngeal carcinoma. Due to the publication of new trials on induction chemotherapy, we updated the network meta-analysis. METHODS: For this individual patient data network meta-analysis, trials of radiotherapy with or without chemotherapy in patients with non-metastatic nasopharyngeal carcinoma that completed accrual before Dec 31, 2016, were identified and updated individual patient data were obtained. Both general databases (eg, PubMed and Web of Science) and Chinese medical literature databases were searched. Overall survival was the primary endpoint. A frequentist network meta-analysis approach with a two-step random effect stratified by trial based on hazard ratio Peto estimator was used. Global Cochran Q statistic was used to assess homogeneity and consistency, and p score to rank treatments, with higher scores indicating higher benefit therapies. Treatments were grouped into the following categories: radiotherapy alone, induction chemotherapy followed by radiotherapy, induction chemotherapy without taxanes followed by chemoradiotherapy, induction chemotherapy with taxanes followed by chemoradiotherapy, chemoradiotherapy, chemoradiotherapy followed by adjuvant chemotherapy, and radiotherapy followed by adjuvant chemotherapy. This study is registered with PROSPERO, CRD42016042524. FINDINGS: The network comprised 28 trials and included 8214 patients (6133 [74·7%] were men, 2073 [25·2%] were women, and eight [0·1%] had missing data) enrolled between Jan 1, 1988, and Dec 31, 2016. Median follow-up was 7·6 years (IQR 6·2-13·3). There was no evidence of heterogeneity (p=0·18), and inconsistency was borderline (p=0·10). The three treatments with the highest benefit for overall survival were induction chemotherapy with taxanes followed by chemoradiotherapy (hazard ratio 0·75; 95% CI 0·59-0·96; p score 92%), induction chemotherapy without taxanes followed by chemoradiotherapy (0·81; 0·69-0·95; p score 87%), and chemoradiotherapy followed by adjuvant chemotherapy (0·88; 0·75-1·04; p score 72%), compared with concomitant chemoradiotherapy (p score 46%). INTERPRETATION: The inclusion of new trials modified the conclusion of the previous network meta-analysis. In this updated network meta-analysis, the addition of either induction chemotherapy or adjuvant chemotherapy to chemoradiotherapy improved overall survival over chemoradiotherapy alone in nasopharyngeal carcinoma. FUNDING: Institut National du Cancer and Ligue Nationale Contre le Cancer.
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Quimioradioterapia , Neoplasias Nasofaríngeas , Masculino , Humanos , Femenino , Carcinoma Nasofaríngeo/tratamiento farmacológico , Metaanálisis en Red , Quimioterapia Adyuvante , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioterapia de Inducción , Neoplasias Nasofaríngeas/tratamiento farmacológico , Neoplasias Nasofaríngeas/radioterapia , Taxoides/uso terapéutico , NasofaringeRESUMEN
Importance: The long-term outcomes associated with adding bevacizumab, a vascular endothelial growth factor inhibitor, to standard chemoradiation have continued to be favorable for a group of patients with locoregionally advanced nasopharyngeal carcinoma (NPC). Objective: To assess long-term toxic effects and clinical outcomes associated with chemotherapy, radiation therapy (RT), and bevacizumab for NPC. Design, Setting, and Participants: This single-arm phase II nonrandomized controlled trial was conducted by the National Cancer Trials Network group and NRG Oncology (formerly Radiation Therapy Oncology Group), with accrual from December 13, 2006, to February 5, 2009, and data analysis from June 26 to July 1, 2019. The study was conducted at 19 cancer centers with a median (IQR) follow-up of 9.0 (7.7-9.3) years. Included patients were adults (aged ≥18 years) with NPC that was World Health Organization (WHO) histologic grade I to IIb or III, American Joint Committee on Cancer stage IIB or greater, and with or without lymph node involvement. Interventions: Patients received 3 cycles of bevacizumab (15 mg/kg) concurrently with standard cisplatin (100 mg/m2) and RT (69.96 Gy) followed by 3 cycles of adjuvant bevacizumab (15 mg/kg) given concurrently with cisplatin (80 mg/m2) and fluorouracil (1000 mg/m2/d). Main Outcomes and Measures: The primary end point was grade 4 hemorrhage or grade 5 adverse events in the first year. Secondary end points were locoregional progression-free (LRPF) interval, distant metastasis-free (DMF) interval, progression-free survival (PFS), overall survival (OS), and other adverse events. Long-term toxic effects and clinical outcomes were reported due to the limited follow-up in the initial report for this trial and the importance of long-term outcomes when combining bevacizumab with chemoradiation. Results: Among 46 patients with NPC who were enrolled, 44 patients were analyzed (29 males [65.9%]; 23 Asian [52.3%], 2 Black [4.5%], and 16 White [36.4%]; 38 not Hispanic [86.4%]; median [IQR] age, 48.5 [39.0-56.0] years). There were 33 patients with a Zubrod performance status of 0, indicating that they were fully functional and asymptomatic (75.0%); 32 patients with a WHO histologic grade of IIb or III (72.7%); and 39 patients with stage III or IVB disease (88.6%). Among analyzed patients, 42 individuals received radiation therapy of 69.96 Gy or greater (95.5%; dose range, 65.72-70.00 Gy); 30 patients received 3 cycles of cisplatin (68.2%) with RT, and 31 patients received 3 cycles of bevacizumab with RT (70.5%); this was followed by 3 cycles of adjuvant cisplatin in 21 patients (47.7%), fluorouracil in 24 patients (54.5%), and bevacizumab in 23 patients (52.3%). No grade 4 hemorrhage or grade 5 AEs were reported in the first year or thereafter. Late grade 3 AEs occurred in 16 patients (36.4%), including 7 patients with dysphagia (15.9%), 6 patients with hearing impairment (13.6%), and 2 patients with dry mouth (4.5%). The 1- and 5-year rates of feeding tube use were 5 of 41 patients (12.2%) and 0 of 27 patients, respectively. There were 19 patients (43.2%) who progressed or died without disease progression (6 patients with locoregional progression [13.6%], 8 patients with distant progression [18.2%], and 5 patients who died without progression [11.4%]). The 5- and 7-year rates were 79.5% (95% CI, 67.6%-91.5%) and 69.7% (95% CI, 55.9%-83.5%) for OS, 61.2% (95% CI, 46.8%-75.6%) and 56.3% (95% CI, 41.5%-71.1%) for PFS, 74.9% (95% CI, 61.4%-86.6%) and 72.3% (95% CI, 58.4%-84.7%) for LRPF interval, and 79.5% (95% CI,66.4%-90.0%) for both times for DMF interval. Among 13 patients who died, death was due to disease in 8 patients (61.5%). Conclusions and Relevance: In this nonrandomized controlled trial, no grade 4 hemorrhage or grade 5 AEs were reported in the first year or thereafter among patients with NPC receiving bevacizumab combined with chemoradiation. The rate of distant metastasis was low although 89% of patients had stage III to IVB disease, suggesting that further investigation may be warranted. Trial Registration: ClinicalTrials.gov Identifier: NCT00408694.
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Cisplatino , Neoplasias Nasofaríngeas , Adulto , Masculino , Humanos , Adolescente , Persona de Mediana Edad , Carcinoma Nasofaríngeo/tratamiento farmacológico , Bevacizumab/efectos adversos , Cisplatino/efectos adversos , Neoplasias Nasofaríngeas/tratamiento farmacológico , Neoplasias Nasofaríngeas/patología , Factor A de Crecimiento Endotelial Vascular , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Fluorouracilo/uso terapéuticoRESUMEN
Cell-free DNA (cfDNA) fragmentation is nonrandom, at least partially mediated by various DNA nucleases, forming characteristic cfDNA end motifs. However, there is a paucity of tools for deciphering the relative contributions of cfDNA cleavage patterns related to underlying fragmentation factors. In this study, through non-negative matrix factorization algorithm, we used 256 5' 4-mer end motifs to identify distinct types of cfDNA cleavage patterns, referred to as "founder" end-motif profiles (F-profiles). F-profiles were associated with different DNA nucleases based on whether such patterns were disrupted in nuclease-knockout mouse models. Contributions of individual F-profiles in a cfDNA sample could be determined by deconvolutional analysis. We analyzed 93 murine cfDNA samples of different nuclease-deficient mice and identified six types of F-profiles. F-profiles I, II, and III were linked to deoxyribonuclease 1 like 3 (DNASE1L3), deoxyribonuclease 1 (DNASE1), and DNA fragmentation factor subunit beta (DFFB), respectively. We revealed that 42.9% of plasma cfDNA molecules were attributed to DNASE1L3-mediated fragmentation, whereas 43.4% of urinary cfDNA molecules involved DNASE1-mediated fragmentation. We further demonstrated that the relative contributions of F-profiles were useful to inform pathological states, such as autoimmune disorders and cancer. Among the six F-profiles, the use of F-profile I could inform the human patients with systemic lupus erythematosus. F-profile VI could be used to detect individuals with hepatocellular carcinoma, with an area under the receiver operating characteristic curve of 0.97. F-profile VI was more prominent in patients with nasopharyngeal carcinoma undergoing chemoradiotherapy. We proposed that this profile might be related to oxidative stress.
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Ácidos Nucleicos Libres de Células , Humanos , Ratones , Animales , Ácidos Nucleicos Libres de Células/genética , Desoxirribonucleasas/genética , Ratones Noqueados , Endonucleasas/genética , Fragmentación del ADN , Endodesoxirribonucleasas/genéticaRESUMEN
Radiotherapy (RT) is the standard-of-care for Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC), where the post-RT clearance of plasma EBV DNA is prognostic. Currently, it is not known whether the post-RT clearance of plasma EBV DNA is related to the presence of circulating T-cell subsets. Blood samples from NPC patients were used to assess the frequency of T-cell subsets relating to differentiation, co-signaling and chemotaxis. Patients with undetectable versus detectable plasma EBV DNA levels post-RT were categorized as clearers vs. non-clearers. Clearers had a lower frequency of PD1+CD8+ T cells as well as CXCR3+CD8+ T cells during RT compared to non-clearers. Clearers exclusively showed a temporal increase in chemo-attractant receptors CCR1, 4 and/or 5, expressing CD8+ T cells upon RT. The increase in CCR-expressing CD8+ T cells was accompanied by a drop in naïve CD8+ T cells and an increase in OX40+CD8+ T cells. Upon stratifying these patients based on clinical outcome, the dynamics of CCR-expressing CD8+ T cells were in concordance with the non-recurrence of NPC. In a second cohort, non-recurrence associated with higher quantities of circulating CCL14 and CCL15. Collectively, our findings relate plasma EBV DNA clearance post-RT to T-cell chemotaxis, which requires validation in larger cohorts.
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A meeting of experts was held in November 2021 to review and discuss available data on performance of Epstein-Barr virus (EBV)-based approaches to screen for early stage nasopharyngeal carcinoma (NPC) and methods for the investigation and management of screen-positive individuals. Serum EBV antibody and plasma EBV DNA testing methods were considered. Both approaches were found to have favorable performance characteristics and to be cost-effective in high-risk populations. In addition to endoscopy, use of magnetic resonance imaging (MRI) to investigate screen-positive individuals was found to increase the sensitivity of NPC detection with minimal impact on cost-effectiveness of the screening program.
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Carcinoma , Infecciones por Virus de Epstein-Barr , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/diagnóstico , Neoplasias Nasofaríngeas/diagnóstico , Herpesvirus Humano 4/genética , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/diagnóstico , Detección Precoz del Cáncer/métodos , ADN Viral/genéticaRESUMEN
Peptides/small proteins, encoded by noncanonical open reading frames (ORF) of previously claimed non-coding RNAs, have recently been recognized possessing important biological functions, but largely uncharacterized. 1p36 is an important tumor suppressor gene (TSG) locus frequently deleted in multiple cancers, with critical TSGs like TP73, PRDM16, and CHD5 already validated. Our CpG methylome analysis identified a silenced 1p36.3 gene KIAA0495, previously thought coding long non-coding RNA. We found that the open reading frame 2 of KIAA0495 is actually protein-coding and translating, encoding a small protein SP0495. KIAA0495 transcript is broadly expressed in multiple normal tissues, but frequently silenced by promoter CpG methylation in multiple tumor cell lines and primary tumors including colorectal, esophageal and breast cancers. Its downregulation/methylation is associated with poor survival of cancer patients. SP0495 induces tumor cell apoptosis, cell cycle arrest, senescence and autophagy, and inhibits tumor cell growth in vitro and in vivo. Mechanistically, SP0495 binds to phosphoinositides (PtdIns(3)P, PtdIns(3,5)P2) as a lipid-binding protein, inhibits AKT phosphorylation and its downstream signaling, and further represses oncogenic AKT/mTOR, NF-κB, and Wnt/ß-catenin signaling. SP0495 also regulates the stability of autophagy regulators BECN1 and SQSTM1/p62 through modulating phosphoinositides turnover and autophagic/proteasomal degradation. Thus, we discovered and validated a 1p36.3 small protein SP0495, functioning as a novel tumor suppressor regulating AKT signaling activation and autophagy as a phosphoinositide-binding protein, being frequently inactivated by promoter methylation in multiple tumors as a potential biomarker.
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ARN Largo no Codificante , Humanos , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosforilación , Metilación de ADN/genética , Proteínas Portadoras/metabolismo , Genes Supresores de Tumor , Proliferación Celular/genética , Línea Celular Tumoral , Vía de Señalización Wnt , Autofagia/genética , Regulación Neoplásica de la Expresión Génica , ADN Helicasas/metabolismo , Proteínas del Tejido Nervioso/metabolismoRESUMEN
INTRODUCTION: The long-term clinical outcomes in biopsy proven IgAN patients treated with aliskiren on top of a maximally tolerated dose of ACEi/ARB remain unknown. METHODS: Patients with IgAN treated with a direct renin inhibitor and ACEi/ARB for at least 6 months were compared with a 1:1 propensityscore-matched cohort (including MEST-C score and the 12-months pre-exposure slope of eGFR matching) who received ACEi/ARB without aliskiren exposure to compute the hazard ratio of reaching the primary endpoint of a composite of 40% reduction in eGFR, initiation of KRT and all-cause mortality. Secondary outcome measures included changes in mean UPCR, blood pressure, eGFR, incidence of hyperkalemia and other adverse events during follow-up. RESULTS: After a median follow-up of 2.5 years, 8/36 (22.2%) aliskiren-treated patients and 6/36 (16.7%) control patients reached the primary composite outcome (HR = 1.60; 95% CI 0.52-4.88; P = 0.412). Aliskiren treatment increased the risk of ≥ 40% eGFR decline (HR = 1.60; 95% CI 0.52-4.88; P = 0.412), and hyperkalemia (HR = 8.60; 95% CI 0.99-73.64; P = 0.050). At 10.8 years, renal composite outcome was reached in 69.4% vs 58.3% (HR = 2.16; 95% CI 1.18-3.98; P = 0.013) of patients in the aliskiren and control groups, respectively. The mean UPCR reduction between treatment and control was not statistically different (52.7% vs 42.5%; 95% CI 0.63-2.35; P = 0.556). The mean intergroup difference in eGFR decline over 60 months was 7.75 ± 3.95 ml/min/1.73 m2 greater in the aliskiren group (12.83 vs 5.08; 95% CI - 0.17 to 15.66; P = 0.055). CONCLUSION: Among patients with IgAN, add-on aliskiren was associated with less favorable long-term kidney outcomes despite an initial anti-proteinuric effect.
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Glomerulonefritis por IGA , Hiperpotasemia , Humanos , Renina , Estudios de Cohortes , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Antagonistas de Receptores de Angiotensina/uso terapéutico , Glomerulonefritis por IGA/complicaciones , Glomerulonefritis por IGA/tratamiento farmacológico , Hiperpotasemia/tratamiento farmacológico , Puntaje de Propensión , Amidas/efectos adversos , Fumaratos/efectos adversosRESUMEN
BACKGROUND: We previously conducted a prospective study to show that nasopharyngeal cancer (NPC) screening with circulating EpsteinBarr virus (EBV) DNA analysis can improve survival. However, the long-term significance of positive results in individuals without cancer was unclear. METHODS: We conducted a second-round screening at a median of 43 months after the initial screening. Participants with detectable plasma EBV DNA were retested in 4 weeks, and those with persistently positive results were investigated with nasal endoscopy and magnetic resonance imaging. RESULTS: Of the 20,174 volunteers who participated in the first-round screening, 17,838 (88.6%) were rescreened. Among them, 423 (2.37%) had persistently detectable plasma EBV DNA. Twenty-four patients were identified as having NPC. A significantly higher proportion of patients had stage I/II cancer than in a historical cohort (67% vs. 20%; chi-square test, P<0.001), and they had superior 3-year progression-free survival (100% vs. 78.8%). Compared with participants with undetectable plasma EBV DNA in the first round of screening, participants with transiently and persistently positive results in the first round were more likely to have a cancer identified in the second round, with relative risks of 4.4 (95% confidence interval, 1.3 to 15.0) and 16.8 (95% confidence interval, 5.7 to 49.6), respectively. CONCLUSIONS: Individuals with detectable plasma EBV DNA but without an immediately identifiable NPC were more likely to have the cancer identified in another round of screening performed 3 to 5 years later. (Funded by Kadoorie Charitable Foundation and others; ClinicalTrials.gov number, NCT02063399.)
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Infecciones por Virus de Epstein-Barr , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/diagnóstico , Herpesvirus Humano 4/genética , Pronóstico , ADN ViralRESUMEN
Objective.To study the effects of magnetic field gradients on the dose deposition in an inhomogeneous medium and to present the benefits offered by magnetic-field-modulated radiotherapy (MagMRT) under multiple radiation beams.Approach.Monte Carlo simulations were performed using the Geant4 simulation toolkit with a 7 MV photon beam from an Elekta Unity system. A water cuboid embedded with material slabs of water, bone, lung or air was used to study the effects of MagMRT within inhomogeneous medium. Two cylindrical water phantoms, with and without a toroidal lung insert embedded, were used to study the effects of MagMRT under single, opposing or four cardinal radiation beams. Optimized magnetic field variations in the form of a wavelet were used to induce dose modulation within the material slabs or at the iso-center of the phantoms.Main results.The magnitudes of the dose enhancement and reduction induced by the magnetic field gradients become more prominent in a medium of lower density. A maximum dose increase of 6.5% and a decrease of 4.8% were found inside bone, while an increase of 20.4% and a decrease of 13.9% were found in lung tissue. Under multiple radiation beams, the dose enhancement can be induced at the iso-center while the dose reduction occurs in regions around the tumor. For the case with four cardinal beams irradiating a homogeneous water cylinder, an 8.4% of dose enhancement and a 2.4% of dose reduction were found. When a toroidal lung insert was embedded, a maximum dose enhancement of 9.5% and a reduction of 17.0% were produced for anterior-posterior opposing fields.Significance.With an optimized magnetic field gradient, MagMRT can induce a dose boost to the target while producing a better sparing to the surrounding normal tissue, resulting in a sharper dose fall-off in all directions outside the target volume.
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Pulmón , Campos Magnéticos , Pulmón/efectos de la radiación , Método de Montecarlo , Fantasmas de Imagen , AguaRESUMEN
Patients with kidney failure who require kidney replacement therapy (KRT) have been increasing globally. Home-based therapies, such as peritoneal dialysis (PD), allow patients to undergo KRT in the home environment, alleviating treatment costs, patient transport, and hospital admission. Peritoneal dialysis-related peritonitis is still the most frequent complication of PD and is often related to technique failure, which can result in PD failure, transfer to hemodialysis, or mortality. The cause of technique failure is multifactorial, and a portion of technique failure is due to underlying physical or cognitive disabilities. There are several connection devices that have been developed to reduce CAPD-related peritonitis. These connection devices are reviewed in this article.
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Progress in the treatment of diabetic kidney disease (DKD) has been modest since the early trials on renin-angiotensin-aldosterone system inhibitors (RAASis). Although sodium-glucose co-transporter 2 inhibitors (SGLT2is) have revolutionized the management of DKD by lowering proteinuria and protecting organs, other novel treatment approaches with good evidence and efficacy that can be used in conjunction with a RAASi or SGLT2i in managing DKD have emerged in the past few years. This review discusses the evidence for glucagon-like peptide-1 receptor agonist, selective mineralocorticoid receptor antagonist, and selective endothelin A receptor antagonist, emerging treatment options for DKD beyond SGLT2 inhibition.
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PURPOSE: To evaluate the effect of material assignment in nasal cavity on dose calculation for the volumetric modulated arc therapy (VMAT) of nasopharyngeal carcinoma (NPC) using Acuros XB (AXB) algorithm. METHODS: The VMAT plans of 30 patients with NPC were calculated using AXB with material auto-assignment of nasal cavity to lung and reassignment to air respectively. The doses to the planning target volumes (PTVs) overlapping with nasal cavity with material auto-assignment of lung (AXB_Lung) were compared to the values obtained when nasal cavity was reassigned to air (AXB_Air) under the dose-to-medium (Dm ) reporting mode of AXB. RESULTS: For dose calculated under AXB_Lung, the D98% , D2% , and Dmean of the PTV69.96 _Air Cavity (PTV of prescription dose 69.96 Gy overlapping with nasal cavity) were on average 16.1%, 1.6%, and 8.6% larger than that calculated under AXB_Air, respectively. Up to 19.5% difference in D98% , 3% difference in D2% , and 11.2% difference in Dmean were observed in the worst cases for PTV69.96 . Similar trend was observed for the PTV5940 _Air Cavity, in which the D98% , D2% , and Dmean calculated under AXB_Lung were on average 14.7%, 2.5%, and 10.2% larger than that calculated under AXB_Air, respectively. In the worst cases, the difference observed in D98% , D2% , and Dmean could be up to 17.7%, 4.5%, and 12.7%, respectively. CONCLUSIONS: Significant dose difference calculated by AXB between the material assignment of lung and air in nasal cavity for NPC cases might imply the possibility of underdosage to the PTVs that overlap with inhomogeneity. Therefore, attention should be put to ensure that accurate material assignment for dose calculation under AXB such that optimal dosage was given for tumor control.
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Neoplasias Nasofaríngeas , Radioterapia de Intensidad Modulada , Algoritmos , Humanos , Cavidad Nasal , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Fantasmas de Imagen , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por ComputadorRESUMEN
PURPOSE: The current recommendation for patients with locoregionally advanced nasopharyngeal carcinoma (NPC) is cisplatin-based induction chemotherapy (IC) or adjuvant chemotherapy (AC) plus concurrent chemoradiotherapy (CRT). However, data on the optimal platinum doses for each phase of combined regimens are lacking. EXPERIMENTAL DESIGN: 742 patients with NPC in the NPC-0501 trial treated with CRT plus IC/AC and irradiated with intensity-modulated radiotherapy (IMRT) were analyzed. The optimal platinum dose to achieve the best overall survival (OS) in the concurrent and induction/adjuvant phases was studied. RESULTS: Evaluation of the whole series shows the optimal platinum dose was 160 mg/m2 in the concurrent and 260 mg/m2 in the induction/adjuvant phase. Repeating the analyses on 591 patients treated with cisplatin throughout (no replacement by carboplatin) confirmed the same results. The cohort with optimal platinum doses in both phases had better OS than the cohort suboptimal in both phases (stage III: 90% vs. 75%; stage IVA-B: 80% vs. 56%, at 5-year). Multivariable analyses confirmed optimal platinum doses in both phases versus suboptimal dose in each phase are significant independent factors for OS, with HR of 0.61 [95% confidence interval (CI), 0.41-0.91] and 0.67 (95% CI, 0.48-0.94), respectively. Treatment sequence was statistically insignificant after adjusting for platinum doses. CONCLUSIONS: Both concurrent and IC/AC are needed for locoregionally advanced NPC, even for patients irradiated by IMRT; the concurrent platinum dosage could be set at ≥160 mg/m2 when coupled with adequate induction/adjuvant dosage at ≥260 mg/m2 (or at least ≥240 mg/m2). To achieve these optimal dosages, IC-CRT at conventional fractionation is favored.
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Neoplasias Nasofaríngeas , Radioterapia de Intensidad Modulada , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Quimioradioterapia/métodos , Quimioterapia Adyuvante , Cisplatino , Fluorouracilo , Humanos , Quimioterapia de Inducción/métodos , Carcinoma Nasofaríngeo/tratamiento farmacológico , Carcinoma Nasofaríngeo/etiología , Neoplasias Nasofaríngeas/tratamiento farmacológico , Neoplasias Nasofaríngeas/radioterapia , Platino (Metal)/uso terapéuticoAsunto(s)
Glomeruloesclerosis Focal y Segmentaria , Insuficiencia Renal Crónica , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Compuestos de Bencidrilo , Glomeruloesclerosis Focal y Segmentaria/tratamiento farmacológico , Glucósidos , Humanos , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéuticoRESUMEN
Locally advanced and recurrent/ metastatic (R/M) head and neck cancers have poor prognosis generally. Radiotherapy (RT) is known to have multiple immunomodulatory effects, and various immune checkpoint inhibitors (ICIs) have been shown to be efficacious in the R/M setting in recent years. Hence, it is logical to combine RT and ICIs to improve the outlook for such patients, especially in view of the promising pre-clinical data on this novel combination. In this review, we highlighted the key mechanisms underlying the immunostimulatory and immunoinhibitory effects of RT, with a view to suggesting strategies to overcome radioresistance. We also discussed how the unique immune landscapes of virus-induced cancers, namely Epstein-Barr virus-induced nasopharyngeal carcinoma and human papillomavirus-mediated oropharyngeal cancer, could be exploited with ICIs. The landmark clinical trials in both the locally advanced and R/M settings were reviewed, and these trials showed that the combination of RT and ICIs is generally well tolerated. The potential reasons behind the largely negative results of these studies were also explored, focusing on various parameters including dose fractionation, sequencing, irradiated volume and the use of predictive biomarkers.