RESUMO
Background: Understanding of changes in salivary and lacrimal gland functions after radioactive iodine therapy (131I-therapy) remains limited, and, to date, no studies have evaluated dose-response relationships between absorbed dose from 131I-therapy and dysfunctions of these glands. This study investigates salivary/lacrimal dysfunctions in differentiated thyroid cancer (DTC) patients six months after 131I-therapy, identifies 131I-therapy-related risk factors for salivary/lacrimal dysfunctions, and assesses the relationships between 131I-therapy radiation dose and these dysfunctions. Methods: A cohort study was conducted involving 136 DTC patients treated by 131I-therapy of whom 44 and 92 patients received 1.1 and 3.7 GBq, respectively. Absorbed dose to the salivary glands was estimated using a dosimetric reconstruction method based on thermoluminescent dosimeter measurements. Salivary and lacrimal functions were assessed at baseline (T0, i.e., immediately before 131I-therapy) and six months later (T6) using validated questionnaires and salivary samplings, with and without stimulation of the salivary glands. Statistical analyses included descriptive analyses and random-effects multivariate logistic and linear regressions. Results: There was no difference between T0 and T6 in the level of parotid gland pain, nor was there difference in the number of patients with hyposalivation, but there were significantly more patients with dry mouth sensation and dry eyes after therapy compared with baseline. Age, menopause, depression and anxiety symptoms, history of systemic disease, and not taking painkillers in the past three months were found to be significantly associated with salivary or lacrimal disorders. Significant associations were found between 131I-exposure and salivary disorders adjusted on the previous variables: for example, per 1-Gy increase in mean dose to the salivary glands, odds ratio = 1.43 [CI 1.02 to 2.04] for dry mouth sensation, ß = -0.08 [CI -0.12 to -0.02] mL/min for stimulated saliva flow, and ß = 1.07 [CI 0.42 to 1.71] mmol/L for salivary potassium concentration. Conclusions: This study brings new knowledge on the relationship between the absorbed dose to the salivary glands from 131I-therapy and salivary/lacrimal dysfunctions in DTC patients six months after 131I-therapy. Despite the findings of some dysfunctions, the results do not show any obvious clinical disorders after the 131I-therapy. Nevertheless, this study raises awareness of the risk factors for salivary disorders, and calls for longer follow-up. Clinical Trials Registration: Number NCT04876287 on the public website (ClinicalTrials.gov).
Assuntos
Aparelho Lacrimal , Doenças das Glândulas Salivares , Neoplasias da Glândula Tireoide , Xerostomia , Feminino , Humanos , Estudos de Coortes , Seguimentos , Radioisótopos do Iodo/efeitos adversos , Aparelho Lacrimal/efeitos da radiação , Neoplasias da Glândula Tireoide/tratamento farmacológico , Xerostomia/induzido quimicamente , Xerostomia/diagnósticoRESUMO
BACKGROUND: Whole brain radiation (WBRT) may lead to acute xerostomia and dry eye from incidental parotid and lacrimal exposure, respectively. We performed a prospective observational study to assess the incidence/severity of this toxicity. We herein perform a secondary analysis relating parotid and lacrimal dosimetric parameters to normal tissue complication probability (NTCP) rates and associated models. METHODS: Patients received WBRT to 25-40 Gy in 10-20 fractions using 3D-conformal radiation therapy without prospective delineation of the parotids or lacrimals. Patients completed questionnaires at baseline and 1 month post-WBRT. Xerostomia was assessed using the University of Michigan xerostomia score (scored 0-100, toxicity defined as ≥ 20 pt increase) and xerostomia bother score (scored from 0 to 3, toxicity defined as ≥ 2 pt increase). Dry eye was assessed using the Subjective Evaluation of Symptom of Dryness (SESoD, scored from 0 to 4, toxicity defined as ≥ 2 pt increase). The clinical data were fitted by the Lyman-Kutcher-Burman (LKB) and Relative Seriality (RS) NTCP models. RESULTS: Of 55 evaluable patients, 19 (35%) had ≥ 20 point increase in xerostomia score, 11 (20%) had ≥ 2 point increase in xerostomia bother score, and 13 (24%) had ≥ 2 point increase in SESoD score. For xerostomia, parotid V10Gy-V20Gy correlated best with toxicity, with AUC 0.68 for xerostomia score and 0.69-0.71 for bother score. The values for the D50, m and n parameters of the LKB model were 22.3 Gy, 0.84 and 1.0 for xerostomia score and 28.4 Gy, 0.55 and 1.0 for bother score, respectively. The corresponding values for the D50, γ and s parameters of the RS model were 23.5 Gy, 0.28 and 0.0001 for xerostomia score and 32.0 Gy, 0.45 and 0.0001 for bother score, respectively. For dry eye, lacrimal V10Gy-V15Gy were found to correlate best with toxicity, with AUC values from 0.67 to 0.68. The parameter values of the LKB model were 53.5 Gy, 0.74 and 1.0, whereas of the RS model were 54.0 Gy, 0.37 and 0.0001, respectively. CONCLUSIONS: Xerostomia was most associated with parotid V10Gy-V20Gy, and dry eye with lacrimal V10Gy-V15Gy. NTCP models were successfully created for both toxicities and may help clinicians refine dosimetric goals and assess levels of risk in patients receiving palliative WBRT.
Assuntos
Irradiação Craniana/efeitos adversos , Síndromes do Olho Seco/etiologia , Lesões por Radiação/etiologia , Xerostomia/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundário , Fracionamento da Dose de Radiação , Relação Dose-Resposta à Radiação , Síndromes do Olho Seco/diagnóstico , Humanos , Aparelho Lacrimal/efeitos da radiação , Pessoa de Meia-Idade , Órgãos em Risco/efeitos da radiação , Glândula Parótida/efeitos da radiação , Probabilidade , Estudos Prospectivos , Lesões por Radiação/diagnóstico , Radioterapia Conformacional/efeitos adversos , Medição de Risco , Xerostomia/diagnóstico , Adulto JovemRESUMO
PURPOSE: We have evaluated the potential radioprotective, antioxidant and anti-apoptotic effects of resveratrol (RSV) against high-dose radioactive iodine (RAI) therapy associated damage of the lacrimal glands by biochemical, histopathological and immunohistochemical methods. MATERIALS AND METHODS: Thirty Wistar-albino rats were randomly divided into three groups; the control group received no treatment or medication, the RAI group received RAI but no medication and the RSV group received oral RAI and intraperitoneal RSV. RSV was started at day one, before RAI administration, and continued for 8 days. Bilateral intraorbital (IG), extraorbital (EG), and Harderian (HG) lacrimal glands were evaluated in all rats for histopathological, immunohistochemical, tissue cytokine and oxidant and antioxidant level assessment. RESULTS: RSV group restored inflammation, fibrosis, vacuolization, change in nucleus characteristics, lipofuscin-like accumulation and cellular morphologic patterns were statistically significant in all lacrimal gland types, compared to the RAI group (p < .05 for all variables). Similarly, elevated Caspase-3 and TUNEL levels in the RAI group were significantly alleviated in the RSV group in all lacrimal gland types (p < .05 for all variables). RAI administration significantly elevated TNF-α, IL-6, NF-кb levels, and decreased IL-10 levels (p < .05 for all parameters) whereas TOS levels significantly increased and TAS levels were significantly decreased. However, RSV significantly diminished TNF-α, IL-6, IL-4, and NF-кb levels. Furthermore, RSV significantly decreased TOS and increased TAS levels (p < .05 for all variables). CONCLUSIONS: We conclude that with its anti-cancer effect as well as its antioxidant effect RSV has protected the histopathological pattern of the lacrimal glands from the damage, decreased inflammation in histopathologic assessments, and decreased tissue cytokine levels, apoptosis and DNA fragmentation on the lacrimal glands after RAI.
Assuntos
Radioisótopos do Iodo/efeitos adversos , Doenças do Aparelho Lacrimal/tratamento farmacológico , Aparelho Lacrimal/patologia , Lesões Experimentais por Radiação/tratamento farmacológico , Resveratrol/farmacologia , Animais , Antioxidantes/farmacologia , Modelos Animais de Doenças , Feminino , Radioisótopos do Iodo/uso terapêutico , Aparelho Lacrimal/metabolismo , Aparelho Lacrimal/efeitos da radiação , Doenças do Aparelho Lacrimal/diagnóstico , Doenças do Aparelho Lacrimal/etiologia , Estresse Oxidativo , Lesões Experimentais por Radiação/complicações , Lesões Experimentais por Radiação/diagnóstico , Ratos , Ratos WistarRESUMO
Aim: The objective of this study was to estimate the absorbed doses to the normal organs and tumor lesions in metastatic castration-resistant prostate cancer (mCRPC) patients treated with indigenously developed 177Lu-PSMA-617 that could establish optimal treatment protocol with minimum risk to the dose-limiting organs. Furthermore, attempt was also made to compare radiation absorbed doses for normal organs and tumor lesions in subsequent cycles of 177Lu-PSMA-617 peptide receptor radioligand therapy (PRLT) in the same group of patients during the course of treatment. Methods: A total of 30 patients of proven mCRPC were enrolled for this prospective study. These patients received up to 5 cycles of treatment with 177Lu-PSMA-617 PRLT (1 cycle for 13 patients, 2 cycles for 9 patients, 3 cycles for 3 patients, and 5 cycles for 5 patients), at 11-12-week intervals between the two successive therapies. The patients underwent postadministration whole-body scintigraphy at five time points: 0.5 (prevoid), 2, 12, 24, and 72/96 h (postvoid). From time-activity curves generated by drawing regions of interests on the images, number of disintegrations was determined. Tumor masses were estimated from pretherapeutic 68Ga-PSMA-11 positron emission tomography-computed tomography images. Absorbed doses for organs and tumors were calculated using OLINDA 2.0 software. Results: The average activity of 177Lu-PSMA-617 (mean ± SD) administered per patient per cycle was 4.94 ± 0.45 GBq. The mean absorbed organ doses (mean ± SD) from first therapy cycle in Gy/GBq were as follows: kidneys 0.52 ± 0.16, spleen 0.17 ± 0.07, liver 0.08 ± 0.05, salivary glands 0.53 ± 0.30, lacrimal glands 1.45 ± 0.85, nasal mucosa membrane 0.46 ± 0.19, urinary bladder 0.23 ± 0.02, and bone marrow 0.04 ± 0.03. The mean effective dose for whole body from first therapy cycle was 0.05 ± 0.03 Sv/GBq. Among all the normal organs, lacrimal glands received the highest absorbed dose. The median dose for all lesions, bone lesions, lymph nodes, primary site, liver lesion, lung lesion, and soft tissue deposit from first therapy cycle was determined to be 4.17, 4.23, 3.96, 4.36, 10.27, 0.78, and 4.68 Gy/GBq respectively. Absorbed doses received by the normal organs in five consecutive cycles follow three different trends, (a) for kidneys, salivary glands, and nasal mucous membrane, absorbed doses increased from first therapy cycle to second therapy cycle and then slowly decreased in subsequently therapy cycles; (b) for spleen, liver, and lacrimal glands, absorbed doses decreased with the successive therapy cycles; and (c) in case of bone marrow, bladder, and whole body, mean absorbed dose almost remained constant in each therapy cycle. Absorbed doses to the lesions gradually decreased with increase of the number of therapy cycles. Conclusions: The organ and tumor absorbed doses of 177Lu-PSMA-617 in mCRPC patients were found to be comparable to the data reported in the literature. The highest absorbed organ dose was observed in lacrimal glands and being a dose limiting organ, a cumulative activity up to 32.5 GBq (878 mCi) of 177Lu-PSMA-617 in 4-5 therapy cycles appears safe and feasible to achieve full therapeutic window.
Assuntos
Dipeptídeos/administração & dosagem , Compostos Heterocíclicos com 1 Anel/administração & dosagem , Lutécio/administração & dosagem , Antígeno Prostático Específico/administração & dosagem , Neoplasias de Próstata Resistentes à Castração/terapia , Lesões por Radiação/prevenção & controle , Radioisótopos/administração & dosagem , Compostos Radiofarmacêuticos/administração & dosagem , Idoso , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Dipeptídeos/efeitos adversos , Relação Dose-Resposta à Radiação , Estudos de Viabilidade , Isótopos de Gálio/administração & dosagem , Radioisótopos de Gálio/administração & dosagem , Compostos Heterocíclicos com 1 Anel/efeitos adversos , Humanos , Aparelho Lacrimal/efeitos da radiação , Masculino , Pessoa de Meia-Idade , Órgãos em Risco/efeitos da radiação , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Estudos Prospectivos , Próstata/diagnóstico por imagem , Próstata/patologia , Antígeno Prostático Específico/efeitos adversos , Lesões por Radiação/etiologia , Radiometria/estatística & dados numéricos , Cintilografia , Compostos Radiofarmacêuticos/efeitos adversosRESUMO
Dry eye syndrome related to radiation therapy is relatively common and can severely impair a patient's daily life. The nuclear factor of activated T cells 5(NFAT5) is well known for its osmoprotective effect under hyperosmolar conditions, and it also has immune-modulating functions. We investigated the role of NFAT5 and the protective effect of α-lipoic acid(ALA) on radiation-induced lacrimal gland (LG) injuries. Rats were assigned to control, ALA only, radiation only, and ALA administered prior to irradiation groups. The head and neck area, including the LG, was evenly irradiated with 2 Gy/minute using a photon 6-MV linear accelerator. NFAT5 expression was enhanced and localized in the LG tissue after irradiation and was related to cellular apoptosis. ALA had a protective effect on radiation-induced LG injury through the inhibition of NFAT5 expression and NFAT5-dependent signaling pathways. Functional radiation-induced damage of the LG and cornea was also restored with ALA treatment. NFAT5 expression and its dependent signaling pathways were deeply related to radiation-induced dry eye, and the condition was improved by ALA treatment. Our results suggest a potential role of NFAT5 and NF-κB in the proinflammatory effect in LGs and cornea, which offers a target for new therapies to treat dry eye syndrome.
Assuntos
Aparelho Lacrimal/efeitos dos fármacos , Lesões por Radiação/tratamento farmacológico , Protetores contra Radiação/uso terapêutico , Ácido Tióctico/uso terapêutico , Fatores de Transcrição/metabolismo , Animais , Aparelho Lacrimal/metabolismo , Aparelho Lacrimal/patologia , Aparelho Lacrimal/efeitos da radiação , Masculino , Lesões por Radiação/metabolismo , Lesões por Radiação/patologia , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/efeitos da radiaçãoRESUMO
PURPOSE: Dry eye is not typically considered a toxicity of whole brain radiation therapy (WBRT). We analyzed dry eye syndrome as part of a prospective study of patient-reported outcomes after WBRT. METHODS AND MATERIALS: Patients receiving WBRT to 25 to 40 Gy were enrolled on a study with dry mouth as the primary endpoint and dry eye syndrome as a secondary endpoint. Patients received 3-dimensional WBRT using opposed lateral fields. Per standard practice, lacrimal glands were not prospectively delineated. Patients completed the Subjective Evaluation of Symptom of Dryness (SESoD, scored 0-4, with higher scores representing worse dry eye symptoms) at baseline, immediately after WBRT (EndRT), and at 1 month (1M), 3 months, and 6 months. Patients with baseline SESoD ≥3 (moderate dry eye) were excluded. The endpoints analyzed were ≥1-point and ≥2-point increase in SESoD score at 1M. Lacrimal glands were retrospectively delineated with fused magnetic resonance imaging scans. RESULTS: One hundred patients were enrolled, 70 were eligible for analysis, and 54 were evaluable at 1M. Median bilateral lacrimal V20Gy was 79%. At 1M, 17 patients (32%) had a ≥1-point increase in SESoD score, and 13 (24%) a ≥2-point increase. Lacrimal doses appeared to be associated with an increase in SESoD score of both ≥1 point (V10Gy: P = .042, odds ratio [OR] 1.09/%; V20Gy: P = .071, OR 1.03/%) and ≥2 points (V10Gy: P = .038, OR 1.15/%; V20Gy: P = .063, OR 1.04/%). The proportion with increase in dry eye symptoms at 1M for lacrimal V20Gy ≥79% versus <79% was 46% versus 15%, respectively, for ≥1 point SESoD increase (P = .02) and 36% versus 12%, respectively, for ≥2 point SESoD increase (P = .056). CONCLUSIONS: Dry eye appears to be a relatively common, dose/volume-dependent acute toxicity of WBRT. Minimization of lacrimal gland dose may reduce this toxicity, and patients should be counseled regarding the existence of this potential side effect and treatments for dry eye.
Assuntos
Neoplasias Encefálicas/radioterapia , Irradiação Craniana/efeitos adversos , Síndromes do Olho Seco/etiologia , Aparelho Lacrimal/efeitos da radiação , Medidas de Resultados Relatados pelo Paciente , Adulto , Idoso , Idoso de 80 Anos ou mais , Irradiação Craniana/métodos , Síndromes do Olho Seco/prevenção & controle , Feminino , Humanos , Aparelho Lacrimal/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Dosagem Radioterapêutica , Xerostomia/etiologia , Adulto JovemRESUMO
Injury to lacrimal glands represents a major health problem after radiation therapy of the head and neck malignancies. Accordingly, this study aimed to investigate significant ultrastructural changes of lacrimal glands and some of their underlying mechanisms following the exposure to different fractionated doses of irradiation. In this study, 28 Sprague Dawley (SD) rats were assigned to four groups (seven rats each): Group I acted as control and received no irradiation. Groups II-IV received fractionated irradiation of 5 Gy (100 cGy/fraction daily for 5 days), 9 Gy (300 cGy/fraction daily for 3 days), and 20 Gy (one fraction), respectively. One month after the experiment, examination of lacrimal glands with transmission electron microscopy (TEM) demonstrated dose-dependent ultrastructural changes in the lacrimal acinar and intralobular ductal epithelial cells. In the acinar cells, there were swollen rough endoplasmic reticulum, irregularly shaped nuclei with chromatin condensation, mitochondrial damage, and retention of secretory granules. Intaralobular ductal epithelial cells showed loss of surface microvilli and damage to mitochondria. In addition to the potential direct effects of irradiation on lacrimal acinar and intralobular ductal epithelial cells, damage to blood vessels and nerve endings seemed to mediate some of the underlying mechanisms of these irradiation-induced ultrastructural changes. In conclusion, using TEM reveals that lacrimal gland is highly sensitive to even small doses of irradiation therapy; in addition, swelling of rough endoplasmic reticulum and aberrant nuclei are the most encountered structural changes. Damage to blood vessels and nerve endings might mediate some of the underlying mechanisms of irradiation-induced secondary injury in lacrimal glands.
Assuntos
Retículo Endoplasmático Rugoso/ultraestrutura , Aparelho Lacrimal/efeitos da radiação , Aparelho Lacrimal/ultraestrutura , Mitocôndrias/ultraestrutura , Lesões por Radiação , Animais , Núcleo Celular/ultraestrutura , Microscopia Eletrônica de Transmissão , Ratos Sprague-DawleyAssuntos
Carcinoma de Apêndice Cutâneo/diagnóstico , Luz Solar/efeitos adversos , Neoplasias das Glândulas Sudoríparas/diagnóstico , Carcinoma de Apêndice Cutâneo/etiologia , Carcinoma de Apêndice Cutâneo/patologia , Carcinoma de Apêndice Cutâneo/cirurgia , Glândulas Écrinas/patologia , Glândulas Écrinas/efeitos da radiação , Glândulas Écrinas/cirurgia , Feminino , Humanos , Aparelho Lacrimal/patologia , Aparelho Lacrimal/efeitos da radiação , Aparelho Lacrimal/cirurgia , Pessoa de Meia-Idade , Neoplasias das Glândulas Sudoríparas/etiologia , Neoplasias das Glândulas Sudoríparas/patologia , Neoplasias das Glândulas Sudoríparas/cirurgia , Resultado do TratamentoRESUMO
BACKGROUND: Some complications of radioiodine therapy have been reported, but the involvement of the eyes and adnexa is rarely discussed. The purpose of this study was to determine the correlation among ocular surface changes, xerostomia, and changes in the nasal mucosa associated with radioiodine therapy. METHODS: Patients subjected to radioiodine therapy (group 1) or not subjected (group 2) were prospectively evaluated by examinations of the ocular surface and tear film, saliva production, and nasal endoscopy. Ocular and nasal symptoms and xerostomia were evaluated using questionnaires. RESULTS: Evaluation of the ocular surface did not indicate significant differences between the groups. Nasal endoscopy revealed higher mucosal pallor in group 1 and worsening of the endoscopic appearance. Worsening of ocular symptoms and nasal symptoms, xerostomia, and a significant decrease in salivary production was also observed in group 1. CONCLUSION: Subjective worsening of xerostomia, xerophthalmia, nasal symptoms, and changes in the nasal mucosa in group 1 was observed.
Assuntos
Adenocarcinoma Folicular/radioterapia , Radioisótopos do Iodo/efeitos adversos , Órgãos em Risco/efeitos da radiação , Neoplasias da Glândula Tireoide/radioterapia , Xerostomia/etiologia , Adenocarcinoma Folicular/patologia , Adulto , Idoso , Estudos de Coortes , Feminino , Seguimentos , Humanos , Radioisótopos do Iodo/uso terapêutico , Aparelho Lacrimal/efeitos da radiação , Masculino , Pessoa de Meia-Idade , Mucosa Nasal/efeitos da radiação , Estudos Prospectivos , Lesões por Radiação/diagnóstico , Lesões por Radiação/epidemiologia , Medição de Risco , Glândulas Salivares/efeitos da radiação , Neoplasias da Glândula Tireoide/patologia , Xeroftalmia/etiologia , Xeroftalmia/fisiopatologia , Xerostomia/fisiopatologiaRESUMO
With improvements in systemic therapy, patients with cancer treated with whole-brain radiotherapy (WBRT) are living long enough to develop late toxicities, including dry eye syndrome. In general practice, dose to the lacrimal gland (LG) is not constrained (maximum constraint <40 Gy) in WBRT. The purpose of this study was to measure dose to the LG in WBRT and determine methods for reducing radiation exposure. We conducted a retrospective review of 70 3-dimensional (3D) conformal plans; thirty-six plans with a radiation prescription of 30 Gy in 10 fractions and 34 plans with a prescription of 37.5 Gy in 15 fractions. LGs were contoured in accordance with Freedman and Sidani (2015). Biological effective dose (BED)3 maximum constraints were calculated from 40 Gy and 20 Gy to be 32.17 Gy (30 Gy) and 36.70 Gy (37.5 Gy). Both regimens demonstrated supraorbital blocking by 3 methods: T1, bordering the supraorbital ridge; T2, no contact with supraorbital ridge; and T3, coverage of the supraorbital ridge. Mean dose for the plans with a 30-Gy prescription and the plans with a 37.5-Gy prescription was 27.5 Gy and 35.2 Gy, respectively (p ≤ 0.0001). BED3 maximum constraint (Dmax) was violated 16 of 26 (61.5%) in T1 (average Dmax: 32.2 Gy), 13 of 28 (46.4%) in T2 (average Dmax: 32.1 Gy), and 5 of 18 (27.8%) in T3 (average Dmax: 31.8 Gy) for the 30-Gy prescription. Dmax was violated in 32 of 32 (100%) in T1 (average Dmax: 40.1 Gy), 22 of 22 (100%) in T2 (average Dmax: 40.3 Gy), and 14 of 14 (100%) in T3 (average Dmax: 39.4) for the 37.5 Gy prescription. Average Dmax for the 37.5-Gy prescription was highly significant in favor of T3 (p = 0.0098). Patients who receive WBRT may develop dry eye syndrome as a late toxicity. Constraints are commonly violated with a prescription of 37.5 Gy. Methods to reduce dose include T3 supraorbital blocking, an easily implementable change that may dramatically improve patient quality of life.
Assuntos
Irradiação Craniana/efeitos adversos , Síndromes do Olho Seco/etiologia , Feminino , Humanos , Aparelho Lacrimal/efeitos da radiação , Masculino , Pessoa de Meia-Idade , Dosagem Radioterapêutica , Estudos Retrospectivos , RiscoRESUMO
PURPOSE: To investigate whether proton therapy (PT) performs safely in superotemporal melanomas, in terms of risk of dry-eye syndrome (DES). METHODS AND MATERIALS: Tumor location, DES grade, and dose to ocular structures were analyzed in patients undergoing PT (2005-2015) with 52 Gy (prescribed dose, not accounting for biologic effectiveness correction of 1.1). Prognostic factors of DES and severe DES (sDES, grades 2-3) were determined with Cox proportional hazard models. Visual acuity deterioration and enucleation rates were compared by sDES and tumor locations. RESULTS: Median follow-up was 44 months (interquartile range, 18-60 months). Of 853 patients (mean age, 64 years), 30.5% had temporal and 11.4% superotemporal tumors. Five-year incidence of DES and sDES was 23.0% (95% confidence interval [CI] 19.0%-27.7%) and 10.9% (95% CI 8.2%-14.4%), respectively. Multivariable analysis showed a higher risk for sDES in superotemporal (hazard ratio [HR] 5.82, 95% CI 2.72-12.45) and temporal tumors (HR 2.63, 95% CI 1.28-5.42), age ≥70 years (HR 1.90, 95% CI 1.09-3.32), distance to optic disk ≥5 mm (HR 2.71, 95% CI 1.52-4.84), ≥35% of retina receiving 12 Gy (HR 2.98, 95% CI 1.54-5.77), and eyelid rim irradiation (HR 2.68, 95% CI 1.49-4.80). The same risk factors were found for DES. Visual acuity deteriorated more in patients with sDES (0.86 ± 1.10 vs 0.64 ± 0.98 logMAR, P=.034) but not between superotemporal/temporal and other locations (P=.890). Enucleation rates were independent of sDES (P=.707) and tumor locations (P=.729). CONCLUSIONS: Severe DES was more frequent in superotemporal/temporal melanomas. Incidence of vision deterioration and enucleation was no higher in patients with superotemporal melanoma than in patients with tumors in other locations. Tumor location should not contraindicate PT.
Assuntos
Síndromes do Olho Seco/etiologia , Melanoma/patologia , Melanoma/radioterapia , Terapia com Prótons/efeitos adversos , Neoplasias Uveais/patologia , Neoplasias Uveais/radioterapia , Fatores Etários , Contraindicações , Síndromes do Olho Seco/epidemiologia , Enucleação Ocular/estatística & dados numéricos , Feminino , Seguimentos , Humanos , Incidência , Aparelho Lacrimal/efeitos da radiação , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Terapia com Prótons/métodos , Dosagem Radioterapêutica , Fatores de Tempo , Acuidade Visual/efeitos da radiaçãoRESUMO
PURPOSE:: To investigate the short-term (1 week) and long-term (8 weeks) protective effects of zinc administration on radioiodine (RAI)-induced lacrimal gland damage of rats. METHODS:: A total of 40 rats were divided into two groups: an RAI group (n=20), which was administrated a single dose of 3 mCi of 131I and 1 mL physiologic saline for 7 days by gastric gavage, and a zinc group (n=20), which received a single dose of 3 mCi of 131I and 1 mL of physiologic saline containing zinc sulfate at a concentration of 10 mg/kg concentration for 7 days by gastric gavage. All rats underwent tear function tests before and 1 week after RAI administration. About 1 week after irradiation, half of the animals in each group were sacrificed and the extraorbital lacrimal glands were removed for histopathological examination. The remaining animals of the groups underwent the same procedures at 8 weeks after irradiation. RESULTS:: In the RAI and zinc groups, the mean tear production was 3.75 ± 1.55 and 3.65 ± 1.53 mm at baseline, 2.10 ± 1.07 and 3.30 ± 1.34 mm at week 1 (p=0.004), and 3.22 ± 1.48 and 3.50 ± 1.78 mm at week 8, respectively; further, the mean corneal fluorescein staining scores were 4.65 ± 2.16 and 4.80 ± 2.21 points at baseline, 7.85 ± 1.90 and 5.45 ± 2.06 points at week 1 (p=0.001), and 5.44 ± 2.13 and 4.90 ± 2.08 at week 8, respectively. The histopathological changes in rat lacrimal glands at weeks 1 and 8 were consistent with the tear function test results. CONCLUSIONS:: Zinc treatment seems to be protective against RAI-induced lacrimal gland damage of rats, particularly in the acute period.
Assuntos
Antioxidantes/administração & dosagem , Radioisótopos do Iodo/efeitos adversos , Aparelho Lacrimal/efeitos dos fármacos , Aparelho Lacrimal/efeitos da radiação , Lesões Experimentais por Radiação/prevenção & controle , Protetores contra Radiação/administração & dosagem , Lágrimas/fisiologia , Sulfato de Zinco/administração & dosagem , Animais , Modelos Animais de Doenças , Feminino , Fluoresceína , Aparelho Lacrimal/patologia , Ratos , Ratos WistarRESUMO
ABSTRACT Purpose: To investigate the short-term (1 week) and long-term (8 weeks) protective effects of zinc administration on radioiodine (RAI)-induced lacrimal gland damage of rats. Methods: A total of 40 rats were divided into two groups: an RAI group (n=20), which was administrated a single dose of 3 mCi of 131I and 1 mL physiologic saline for 7 days by gastric gavage, and a zinc group (n=20), which received a single dose of 3 mCi of 131I and 1 mL of physiologic saline containing zinc sulfate at a concentration of 10 mg/kg concentration for 7 days by gastric gavage. All rats underwent tear function tests before and 1 week after RAI administration. About 1 week after irradiation, half of the animals in each group were sacrificed and the extraorbital lacrimal glands were removed for histopathological examination. The remaining animals of the groups underwent the same procedures at 8 weeks after irradiation. Results: In the RAI and zinc groups, the mean tear production was 3.75 ± 1.55 and 3.65 ± 1.53 mm at baseline, 2.10 ± 1.07 and 3.30 ± 1.34 mm at week 1 (p=0.004), and 3.22 ± 1.48 and 3.50 ± 1.78 mm at week 8, respectively; further, the mean corneal fluorescein staining scores were 4.65 ± 2.16 and 4.80 ± 2.21 points at baseline, 7.85 ± 1.90 and 5.45 ± 2.06 points at week 1 (p=0.001), and 5.44 ± 2.13 and 4.90 ± 2.08 at week 8, respectively. The histopathological changes in rat lacrimal glands at weeks 1 and 8 were consistent with the tear function test results. Conclusions: Zinc treatment seems to be protective against RAI-induced lacrimal gland damage of rats, particularly in the acute period.
RESUMO Objetivo: Investigar se o tratamento com zinco tem efeito protetor, no curto prazo (1 semana) e longo prazo (8 semanas), sobre os danos induzidos na glândula lacrimal por iodo radiotativo (RAI) em ratos. Métodos: Quarenta ratos foram divididos em dois grupos. No grupo RAI (n=20) foi administrada uma única dose de 3 mCi 131I e 1 cc de solução salina fisiológica durante 7 dias, por gavagem gástrica. O grupo zinco (n=20) recebeu uma dose única de 3 mCi 131I e 1 cc de solução salina fisiológica contendo sulfato de zinco na concentração de 10 mg/kg durante 7 dias por gavagem gástrica. Os testes de função lacrimal foram realizadas para todos os animais antes e após uma semana da administração da RAI. Em seguida, após 1 semana da administração, metade dos animais de cada grupo foi sacrificada e as glândulas lacrimais extraorbitais foram removidas para exame histopatológico. Os animais remanescentes dos grupos foram submetidos aos mesmos procedimentos após 8 semanas a radiação. Resultados: As médias de produção lacrimal foram de 3,75 ± 1,55 e 3,65 ± 1,53 mm na linha de base, 2,10 ± 1,07 e 3,30 ± 1,34 mm na 1a semana (p=0,004), e 3,22 ± 1,48 e 3,50 ± 1,78 mm na 8a semana, para os grupos RAI e zinco, respectivamente. As pontuações médias de coloração fluoresceína foram 4,65 ± 2,16 e 4,80 ± 2,21 no início do estudo, 7,85 ± 1,90 e 5,45 ± 2,06 na primeira semana (p=0,001), 5,44 ± 2,13 e 4,90 ± 2,08 pontos na 8a semana, para os grupos RAI e zinco, respectivamente. As alterações histopatológicas das glândulas lacrimais em 1 e 8 semanas foram consistentes com os testes de função lacrimal resultados. Conclusões: O tratamento de zinco parece ser protetor sobre os danos glândula lacrimal induzidos por RAI em ratos, especialmente no período agudo.
Assuntos
Animais , Feminino , Ratos , Lesões Experimentais por Radiação/prevenção & controle , Protetores contra Radiação/administração & dosagem , Radioisótopos do Iodo/efeitos adversos , Aparelho Lacrimal/efeitos dos fármacos , Aparelho Lacrimal/efeitos da radiação , Antioxidantes/administração & dosagem , Lágrimas/fisiologia , Ratos Wistar , Sulfato de Zinco/administração & dosagem , Fluoresceína , Modelos Animais de Doenças , Aparelho Lacrimal/patologiaRESUMO
OBJECTIVE: To establish a radiation-injured model of lacrimal gland in mice and explore its pathophysiology. METHOD: Experimental research. According to the random number table, 50 healthy mice were divided into five groups:one control group (n = 10) and four experimental groups (n = 40). The experimental mice (n = 40) were exposed to different dosages of irradiation 12, 15, 18 and 21 Gy, respectively. The sham-irradiated controls (n = 10) were anesthetized in parallel with the irradiated rats but not irradiated. The mice were placed laterally and covered with a bolus material, then the X-ray irradiation was performed under general anaesthesia from above towards the mice' orbital region. The schirmer tests, Single- photon emission computed tomography/Computed tomography (SPECT/CT), HE, immunohistological, and ultrastructural examinations were conducted prior and 3 days, 7 days as well as 30 days after irradiation.Using t test to compare the differentiation of each group at the same time point. RESULTS: In 12 Gy group, there is no statistically significant decline in tear secretion (3 days after radiation, t = 2.137, P = 0.061;7 days after radiation, t = 1.137, P = 0.243).In 15 Gy group, Schirmer I test showed significantly reduced lachrymal secretion and the difference was statistically significant(3 days after radiation:t = 3.228, P = 0.011;7 days after radiation:t = 4.781, P = 0.001;30 days after radiation:t = 3.162, P = 0.011). Immunohistochemical findings include a significant loss in the expression of α-SMA (3 days after radiation, t = 4.395, P = 0.013; 30 days after radiation, t = 3.049, P = 0.035) , aquaporin (AQP-5) (3 days after radiation, t = 3.587, P = 0.028;30 days after radiation, t = 5.598, P = 0.005) , and an excessive expression of Tenascin-C (3 days after radiation, t = 2.964, P = 0.046;30 days after radiation, t = 4.028, P = 0.017) and CK8 (3 days after radiation, t = 5.103, P = 0.008;30 days after radiation, t = 6.178, P = 0.004) , which were statistically significant. Ultrastructural changes include a retention of secretory granules and an increase of apoptotic acinar nuclei as well as macrophage phagocytosis. Disturbance in the tracer uptake as well as reduction of the lacrimal ejection fraction was assessed under SPET/CT test and the difference was statistically significant (3 days after radiation:t = 2.796, P = 0.029;30 days after radiation:t = 2.641, P = 0.038). This radiation dosage didn't cause obvious eye complications (cataract, radiation retinopathy, etc.). At the dosages of 18 and 21 Gy, the lacrimal gland inflammation and tissue apoptosis expand obviously. CONCLUSIONS: The model of radiation-injured lacrimal gland was successfully constructed. Pathophysiological manifestation include the impaired structures of lacrimal gland cells and infiltration of inflammatory cells, as well as damaged function of tear secretion. These changes may prerequisites for further study on radiological protection of lacrimal glands during radiotherapy of the periorbital region for orbital tumors.
Assuntos
Modelos Animais de Doenças , Aparelho Lacrimal/efeitos da radiação , Lesões por Radiação/patologia , Actinas/metabolismo , Animais , Apoptose , Dacriocistite/patologia , Masculino , Camundongos , Doses de Radiação , Lesões por Radiação/metabolismo , Lesões por Radiação/fisiopatologia , Ratos , Lágrimas/metabolismo , Tenascina/metabolismo , Fatores de TempoRESUMO
Radiation therapy is the most widely used and effective treatment for orbital tumors, but it causes dry eye due to lacrimal gland damage. Induced pluripotent stem cell-derived conditioned medium (iPSC-CM) has been shown to rescue different types of tissue damage. The present study investigated the mechanism of the potential radioprotective effect of IPS cell-derived conditioned medium (iPSC-CM) on gamma-irradiation-induced lacrimal gland injury (RILI) in experimental mice. In this study, we found that iPSC-CM ameliorated RILI. iPSC-CM markedly decreased radiotherapy induced inflammatory processes, predominantly through suppressing p38/JNK signaling. Further signaling pathway analyses indicated that iPSC-CM could suppress Akt (Protein Kinase B, PKB) phosphorylation. High levels of midkine (MDK) were also found in iPSC-CM and could be involved in lacrimal gland regeneration by promoting cell migration and proliferation. Thus, our study indicates that inhibiting the p38/JNK pathway or increasing the MDK level might be a therapeutic target for radiation-induced lacrimal gland injury.
Assuntos
Meios de Cultivo Condicionados/farmacologia , Células-Tronco Pluripotentes Induzidas/metabolismo , Aparelho Lacrimal/efeitos dos fármacos , Aparelho Lacrimal/efeitos da radiação , Lesões Experimentais por Radiação/tratamento farmacológico , Protetores contra Radiação/farmacologia , Animais , Meios de Cultivo Condicionados/isolamento & purificação , Citocinas/isolamento & purificação , Citocinas/farmacologia , Feminino , Proteínas Quinases JNK Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Aparelho Lacrimal/metabolismo , Aparelho Lacrimal/patologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Midkina , Fatores de Crescimento Neural/isolamento & purificação , Fatores de Crescimento Neural/farmacologia , Lesões Experimentais por Radiação/metabolismo , Lesões Experimentais por Radiação/patologia , Protetores contra Radiação/isolamento & purificação , Radioterapia/efeitos adversos , Radioterapia/métodos , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
BACKGROUND: To compare dosimetric parameters of volumetric modulated arc therapy (VMAT) and non-coplanar intensity modulated radiotherapy (IMRT) for nasal cavity and paranasal sinus cancer with regard to the coverage of planning target volume (PTV) and the sparing of organs at risk (OAR). METHODS: Ten patients with nasal cavity or paranasal sinus cancer were re-planned by VMAT (two-arc) plan and non-coplanar IMRT (7-, 11-, and 15-beam) plans. Planning objectives were to deliver 60 Gy in 30 fractions to 95% of PTV, with maximum doses (D(max)) of <50 Gy to the optic nerves, optic chiasm, and brainstem, <40 Gy to the eyes and <10 Gy to the lenses. The target mean dose (D(mean)) to the parotid glands was <25 Gy, and no constraints were applied to the lacrimal glands. Planning was optimized to minimized doses to OAR without compromising coverage of the PTV. VMAT and three non-coplanar IMRT (7-, 11-, and 15-beam) plans were compared using the heterogeneity and conformity indices (HI and CI) of the PTV, D(max) and D(mean) of the OAR, treatment delivery time, and monitor units (MUs). RESULTS: The HI and CI of VMAT plan were superior to those of the 7-, 11-, and 15-beam non-coplanar IMRT. VMAT and non-coplanar IMRT (7-, 11-, and 15-beam) showed equivalent sparing effects for the optic nerves, optic chiasm, brainstem, and parotid glands. For the eyes and lenses, VMAT achieved equivalent or better sparing effects when compared with the non-coplanar IMRT plans. VMAT showed lower MUs and reduced treatment delivery time when compared with non-coplanar IMRT. CONCLUSIONS: In 10 patients with nasal cavity or paranasal sinus cancer, a VMAT plan provided better homogeneity and conformity for PTV than non-coplanar IMRT plans, with a shorter treatment delivery time, while achieving equal or better OAR-sparing effects and using fewer MUs.
Assuntos
Cavidade Nasal/efeitos da radiação , Neoplasias dos Seios Paranasais/radioterapia , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos , Olho/efeitos da radiação , Humanos , Aparelho Lacrimal/efeitos da radiação , Nervo Óptico/efeitos da radiação , Órgãos em Risco/efeitos da radiação , Neoplasias dos Seios Paranasais/patologia , Seios Paranasais/patologia , Seios Paranasais/efeitos da radiação , Glândula Parótida/efeitos da radiação , Radiometria , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/efeitos adversos , Carga TumoralRESUMO
PURPOSE OF THE STUDY: Radioiodine (RAI) has been used for the treatment of hyperthyroidism and well-differentiated thyroid carcinoma for more than 70 years. Lycopene is an anti-oxidant, which is plentiful in red fruits. The purpose of this study was to investigate the possible inhibitory effect of lycopene on the RAI-induced acute histopathological changes in rat lacrimal glands. METHODS: In this experimental animal study, 32 rats were randomly divided into three groups. The first group (control group, n = 8) was not given neither (131)I nor lycopene, the second group (RAI group, n = 12) was administrated a single dose of 3 mCi (131)I and 1 cc physiologic saline by gastric gavage. The third group (lycopene group, n = 12) was administrated 3 mCi (131)I and 1 cc lycopene by gastric gavage. After 24 h of the last dose, the animals were decapitated on the seventh day and their lacrimal glands were removed for histopathological examination. RESULTS: The cell shape and the cell size variation and poorly defined acidophilic cell outlines in all lacrimal glands were observed significantly less frequently in the lycopene group than in the RAI group. CONCLUSIONS: Our histopathological examinations have revealed that lycopene prevents rat lacrimal glands against RAI-related acute histopathological changes.
Assuntos
Carotenoides/administração & dosagem , Radioisótopos do Iodo/administração & dosagem , Doenças do Aparelho Lacrimal/prevenção & controle , Aparelho Lacrimal/patologia , Lesões Experimentais por Radiação/prevenção & controle , Animais , Antioxidantes/administração & dosagem , Antioxidantes/farmacocinética , Carotenoides/farmacocinética , Células Cultivadas , Relação Dose-Resposta a Droga , Relação Dose-Resposta à Radiação , Lavagem Gástrica/métodos , Radioisótopos do Iodo/farmacocinética , Aparelho Lacrimal/metabolismo , Aparelho Lacrimal/efeitos da radiação , Doenças do Aparelho Lacrimal/metabolismo , Doenças do Aparelho Lacrimal/patologia , Licopeno , Lesões Experimentais por Radiação/metabolismo , Lesões Experimentais por Radiação/patologia , Ratos , Ratos WistarRESUMO
BACKGROUND: Radioactive iodine (RAI) therapy is preferred in the treatment of hyperthyroidism because of its effectiveness, noninvasiveness, and low costs. I has been detected in extrathyroidal tissues, such as in gastric mucosa, salivary glands, and lacrimal glands. To the best of our knowledge, there is no publication concerning the effects of RAI therapy for hyperthyroidism on tear production. In the present study, we evaluated whether or not the lacrimal glands are affected after RAI therapy when compared with pretreatment period. METHODS: The Schirmer and tear break-up time (TBUT) tests were used to assess 32 eyes of 16 patients with conditions that were diagnosed as hyperthyroidism before and at 3 and 6 months after RAI treatment. In addition, pretreatment values of patients were compared with that of controls. It was evaluated whether or not a correlation exists between the results and the dose or iodine uptake values. RESULTS: There was no significant difference between pretreatment values of Schirmer and TBUT tests obtained in the patient group and those of the control group (P > 0.05). In the patient group, there was a significant difference between the posttreatment and pretreatment values (P < 0.05). There was a positive correlation between uptake values obtained at 24 hours and the values obtained by TBUT and Schirmer tests on both eyes at 3 and 6 months. At 6 months, the uptake value at 24 hours was 28.83 ± 60 for both eyes in patients with TBUT test values less than 10, whereas it was 39.25 ± 7.88 for the right eye and 39.00 ± 6.85 for the left eyes in patients with TBUT test values greater than 10. The difference was statistically significant (P < 0.05). CONCLUSIONS: In our study, we concluded that the decrease in mucin and aqueous production occurs due to affected lacrimal glands by RAI therapy; however, this effect is not dose dependent.
Assuntos
Hipertireoidismo/radioterapia , Aparelho Lacrimal/fisiologia , Aparelho Lacrimal/efeitos da radiação , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Radioisótopos do Iodo/efeitos adversos , Radioisótopos do Iodo/uso terapêutico , Masculino , Pessoa de Meia-IdadeRESUMO
UNLABELLED: Radioiodine (RAI) is a well-known radionuclide which is used in vivo both for diagnostic and therapeutic purposes, particularly for the treatment of hyperthyroidism and thyroid cancer. Vitamin E is a well-known antioxidant vitamin. The aim of this study was to evaluate whether there was a protective effect of short-term vitamin E on RAI-induced lacrimal gland early damage in experimental animal models. METHODS: Twentyfour rats were randomly divided into two groups. The first group (RAI group) was administreted 3 mCi (131)I by gastric gavage and 1 mL physiological saline intraperitoneally. The second group (RAI + Vitamin E) was administrated 3 mCi (131)I by gastric gavage and 1 mL vitamin E intraperitoneally. After 24 h of the last dose being administered on the 7th day, the animals were decapitated. The lacrimal glands [Intraorbital (IG), extraorbital (EG) and harderian glands (HG)] of the rats were removed for histopathological examination. RESULTS: Periductal and/or periacinar fibrosis in all lacrimal glands were observed to be statistically significantly less frequent in the RAI + Vitamin E group compared to the RAI group. The existence of the abnormal lobular pattern and peripheral basophilia and irregular nucleus shape in IG and in EG, the poorly defined acidophilic cell outline and periductal infiltration in IG and in HG were observed to be statistically significantly less frequent in the RAI + Vitamin E group than in the RAI group. CONCLUSION: According to study results, histopathological examinations revealed that vitamin E protects rat lacrimal glands against RAI-related early damage.