RESUMEN
OBJECTIVE: The aim of this study was to evaluate the early histopathological changes of gastroesophageal reflux and irradiation on laryngeal mucosa in rats. STUDY DESIGN: Animal study. SETTING: Experimental animal laboratory, tertiary referral center. SUBJECT AND METHOD: Twenty-four adult female Wistar Albino rats were grouped as: control (n = 6), reflux and irradiation (n = 10), and irradiation (n = 8). Rats were operated to create a reflux model 30 days before irradiation. Ionizing radiation was administered in a single fraction of a 20 Gy to the larynx. Laryngeal tissue samples were taken at the 4th day of irradiation and all specimens underwent histopathological examination. RESULTS: Edema and vascular dilation in lamina propria were higher in the reflux and irradiation, and irradiation groups than control group. Inflammation was higher in the reflux and irradiation group than the control group. Inflammation in squamous epithelium was higher in the reflux and irradiation and irradiation groups compared to the control group. Inflammation in the squamous epithelium of the irradiation group was higher than the reflux and irradiation group. In the respiratory tract epithelium, inflammation was higher in the reflux and irradiation group; additionally, a significant loss of cilia was present in the reflux and irradiation and irradiation groups while pseudostratification was higher in the reflux and irradiation group. CONCLUSION: Ionizing radiation-induced inflammation may increase on previously inflammated area due to gastroesophageal reflux. Therefore, it may be helpful to investigate and treat the reflux in laryngeal cancer patients that will receive ionizing radiation.
Asunto(s)
Reflujo Gastroesofágico/radioterapia , Mucosa Laríngea/efectos de la radiación , Adulto , Animales , Modelos Animales de Enfermedad , Femenino , Reflujo Gastroesofágico/patología , Humanos , Mucosa Laríngea/patología , Membrana Mucosa/patología , Membrana Mucosa/efectos de la radiación , Ratas , Ratas WistarRESUMEN
OBJECTIVES: The larynx is susceptible to irradiation, which causes significant vocal fold (VF) edema and dehydration shortly after radiotherapy for head and neck cancers. However little is known about radiation-induced damage to VF liquid homeostasis. To evaluate the effects of irradiation on VF hydration and lubrication, we investigated changes in water transporters (aquaporins [AQPs]) and mucin production in vivo and ex vivo, as well as morphometric changes in the laryngeal mucosa and glands of irradiated rat larynges. STUDY DESIGN: Animal study. MATERIALS AND METHODS: Local irradiation at 18 Gy was delivered to rat larynges. Histologic changes in laryngeal mucosa and glands were observed by light microscopy, and the distributions of AQPs and mucin were investigated by immunofluorescence staining 3 months after irradiation. Early effects on gene regulation of AQPs and mucin were evaluated by quantitative real-time polymerase chain reaction of the extirpated VFs and subglottic laryngeal mucosa at 12, 24, and 72 hours after irradiation. RESULTS: Laryngeal glands exhibited severe atrophic changes and showed decreased density throughout the irradiated larynx. The expression of AQP1, 4, 5, and mucin in VFs, as well as AQP5 and mucin in submucosal laryngeal glands, decreased significantly 3 months after irradiation. An ex vivo study revealed that the gene expression of AQP5 in VF tissues was significantly downregulated at 12 hours postirradiation. CONCLUSION: Laryngeal irradiation induces damage in laryngeal mucosal barriers and alters laryngeal liquid homeostasis, which may be one reason for vocal dysfunction following irradiation. LEVEL OF EVIDENCE: N/A.
Asunto(s)
Edema/etiología , Mucosa Laríngea/metabolismo , Neoplasias Laríngeas/radioterapia , Neoplasias Experimentales , Traumatismos Experimentales por Radiación/patología , Pliegues Vocales/efectos de la radiación , Animales , Relación Dosis-Respuesta en la Radiación , Edema/metabolismo , Edema/patología , Estudios de Seguimiento , Homeostasis/efectos de la radiación , Mucosa Laríngea/patología , Mucosa Laríngea/efectos de la radiación , Neoplasias Laríngeas/metabolismo , Neoplasias Laríngeas/patología , Traumatismos Experimentales por Radiación/metabolismo , Ratas , Ratas Sprague-Dawley , Pliegues Vocales/patologíaRESUMEN
PURPOSE: To investigate the individual pattern of acute mucosal radiation reactions (AMRR) in patients with head and neck cancer who were treated with radiotherapy alone. Reactions were evaluated daily on an individual basis according to the Dische scoring system. MATERIALS AND METHODS: Treatment of 87 head and neck cancer patients comprised either conventional fractionation- (CF; n = 33), accelerated fractionation (AF; n = 33), hyperfractionated- (HPEFX; n = 12) or hypofractionated (HPOFX; n = 9) radiotherapy with radical intent. Daily evaluation of AMRR progression was performed prospectively using a modified, morphologically functional Dische scoring system. The daily sums of the score parameters were subsequently used to construct an individual AMRR course curve for each patient. RESULTS: A latency period ranging from 3 to 14 days between the start of radiotherapy and the occurrence of the first AMRR symptom was observed in all patients. Based on the three different shapes of AMRR course curve observed during radiotherapy, three types of AMRR course can be described: (1) a continual increase in AMRR intensity until the completion of radiotherapy; (2) the incidence of a plateau phase following the increase in AMRR (increase-plateau course) and (3) decreasing AMRR intensity with a healing phase. A continual increase in AMRR intensity was observed in about 25 % of CF and AF patients and in more than 50 % of HPOFX treatments. This type of reaction was not observed in the HPEFX group. The increase-plateau course was noted in the majority of AF and CF patients; in almost half of those treated with HPOFX and in all HPEFX patients. A decreasing AMRR intensity course was observed in 23 % of all patients, although not observed at all in the HPEFX and HPOFX fractionation groups. CONCLUSION: The course of AMRR during radiotherapy can differ between individual patients. After the initial increase in AMRR intensity, a stabilization of the reaction--visible as a plateau phase on the course curve--is observed in the majority of patients. A proportion of the irradiated patients experience a continual increase in AMRR intensity up until the end of radiotherapy. A further group of patients exists in whom signs of AMRR healing are observed during the final stages of radiotherapy.
Asunto(s)
Fraccionamiento de la Dosis de Radiación , Mucositis/diagnóstico , Neoplasias de Oído, Nariz y Garganta/radioterapia , Traumatismos por Radiación/diagnóstico , Adulto , Anciano , Progresión de la Enfermedad , Relación Dosis-Respuesta en la Radiación , Femenino , Humanos , Mucosa Laríngea/efectos de la radiación , Masculino , Persona de Mediana Edad , Mucosa Bucal/efectos de la radiación , Estadificación de Neoplasias , Neoplasias de Oído, Nariz y Garganta/patología , Faringe/efectos de la radiación , Estudios ProspectivosRESUMEN
Head-and-neck tumors are often situated at an air-tissue interface what may result in an underdosage of part of the tumor in radiotherapy treatments using megavoltage photons, especially for small fields. In addition to effects of transient electronic disequilibrium, for these small fields, an increased lateral electron range in air will result in an important extra reduction of the central axis dose beyond the cavity. Therefore dose calculation algorithms need to model electron transport accurately. We simulated the trachea by a 2 cm diameter cylindrical air cavity with the rim situated 2 cm beneath the phantom surface. A 6 MV photon beam from an Elekta SLiplus linear accelerator, equipped with the standard multileaf collimator (MLC), was assessed. A 10 x 2 cm2 and a 10 x 1 cm2 field, both widthwise collimated by the MLC, were applied with their long side parallel to the cylinder axis. Central axis dose rebuild-up was studied. Radiochromic film measurements were performed in an in-house manufactured polystyrene phantom with the films oriented either along or perpendicular to the beam axis. Monte Carlo simulations were performed with BEAM and EGSnrc. Calculations were also performed using the pencil beam (PB) algorithm and the collapsed cone convolution (CCC) algorithm of Helax-TMS (MDS Nordion, Kanata, Cahada) version 6.0.2 and using the CCC algorithm of Pinnacle (ADAC Laboratories, Milpitas, CA, USA) version 4.2. A very good agreement between the film measurements and the Monte Carlo simulations was found. The CCC algorithms were not able to predict the interface dose accurately when lateral electronic disequilibrium occurs, but were shown to be a considerable improvement compared to the PB algorithm. The CCC algorithms overestimate the dose in the rebuild-up region. The interface dose was overestimated by a maximum of 31% or 54%, depending on the implementation of the CCC algorithm. At a depth of 1 mm, the maximum dose overestimation was 14% or 24%.
Asunto(s)
Mucosa Laríngea/efectos de la radiación , Método de Montecarlo , Radioterapia Conformacional/métodos , Película para Rayos X , Aire , Algoritmos , Electrones , Neoplasias de Cabeza y Cuello/radioterapia , Humanos , Modelos Teóricos , Fantasmas de Imagen , Poliestirenos , Radiometría , Planificación de la Radioterapia Asistida por ComputadorRESUMEN
Although radiotherapy is often used to treat laryngeal carcinoma, there is little information on the effects of this treatment on laryngeal structures. Rats were irradiated to the head and neck region and the larynges were studied by light- and electron-microscopy and immunohistochemistry. Ten days after irradiation, a change in the ultrastructural appearance of the granules of the subglottic glands was observed. Substance P-, bombesin- and enkephalin-like immunoreactivity was increased in local ganglionic cells and glandular nerve fibres. The mast cells were reduced in number. At examination 4 6 months after irradiation, there were no obvious differences compared with controls concerning mast-cell numbers and neuropeptide expression. The ultrastructural changes seen in the subglottic glands remained to some extent. The results show that structural changes in the subglottic glands occur concomitantly with an increased expression of certain neuropeptides in the innervation of these glands, which implies a relationship between these two parameters. The mast cells respond drastically to irradiation, but in the long run, regeneration of these cells occurs.
Asunto(s)
Mucosa Laríngea/efectos de la radiación , Animales , Bombesina/análisis , Péptido Relacionado con Gen de Calcitonina/análisis , Recuento de Células , Encefalinas/análisis , Femenino , Inmunohistoquímica , Mucosa Laríngea/química , Mucosa Laríngea/patología , Mucosa Laríngea/ultraestructura , Mastocitos/patología , Mastocitos/efectos de la radiación , Radioterapia de Alta Energía , Ratas , Ratas Sprague-Dawley , Serotonina/análisis , Sustancia P/análisisRESUMEN
The course and severity of acute mucosal reactions in 22 patients with previously untreated T1-2N0 glottic cancers were compared between two treatment schedules with different dose intensities: accelerated hyperfractionated radiation therapy (AHF) and standard conventional fractionation radiation therapy (CF). AHF consisted of a twice-daily fractionation of 1.5 Gy 10 times weekly to a total dose of 66 Gy given in 30-40 (median, 33) days. For CF, the fractionation was 2 Gy five times weekly for a total dose of 66 Gy in 45-51 (median, 49) days. Both treatment schedules were well tolerated and no treatment interruptions were necessary. The mucosal reaction reached a peak score clearly earlier with AHF than CF and already demonstrated improvement in the final treatment week. In contrast, the reaction persisted with CF. It is suggested that damaged mucosal tissues with AHF can be effectively compensated by enhanced regeneration response due to an adequately high dose intensity, suggesting a possible tolerability advantage for AHF.
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Glotis/efectos de la radiación , Hipofaringe/patología , Mucosa Laríngea/patología , Neoplasias Laríngeas/radioterapia , Traumatismos por Radiación/patología , Radioterapia/efectos adversos , Enfermedad Aguda , Anciano , Fraccionamiento de la Dosis de Radiación , Glotis/patología , Humanos , Hipofaringe/efectos de la radiación , Mucosa Laríngea/efectos de la radiación , Neoplasias Laríngeas/patología , Laringitis/etiología , Laringitis/patología , Masculino , Persona de Mediana Edad , Faringitis/etiología , Faringitis/patología , Traumatismos por Radiación/etiología , Estudios RetrospectivosRESUMEN
We studied laryngeal video stroboscopy (LVS) system for evaluation of patients with glottic carcinoma (T1N0M0) before and after radiotherapy. There were 10 patients with T1 glottic squamous cell carcinoma (9 men and 1 woman) who received radiotherapy at the Hitachi General Hospital. We performed LVS before and after radiotherapy. The presence or absence of mucosal waves (MW) was particularly noted. No MW were present before radiotherapy but at 1-6 months after, MW gradually appeared. One year after radiotherapy all patients showed MW on LVS. In patients with glottic carcinoma MW recovered after radiation therapy. LVS may be useful for the clinical follow-up of post-radiation patients for early detection of recurrence of glottic carcinoma.
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Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/radioterapia , Glotis , Mucosa Laríngea/patología , Neoplasias Laríngeas/patología , Neoplasias Laríngeas/radioterapia , Femenino , Estudios de Seguimiento , Glotis/patología , Glotis/efectos de la radiación , Humanos , Mucosa Laríngea/efectos de la radiación , Laringoscopía , Masculino , Factores de Tiempo , Grabación en VideoRESUMEN
This paper discusses the various forms of altered fractionated radiation therapy programmes which were used in the past and at present. Treatment programmes employing large fraction sizes and prolonged treatment course result in severe late complication of the normal tissues and inferior local tumour control respectively, and are no longer advised. The current radiobiologic concepts of altered fractionationated treatment are briefly discussed. The experiences of using accelerated hyperfractionated radiation therapy programme for the treatment of oropharyngeal and laryngeal carcinomas at the Massachusetts General Hospital (MGH) from 1979 through 1994 are presented. The programme consists of 1.6 Gy/f twice-daily (BID) for approximately 67.2-70.4 Gy in 6 weeks with a short 'break' after the initial 38.4 Gy. The local control and disease specific survival rates after BID are reported related to the various stages of the lesions and compared with historical control of once-daily (QD) radiation therapy at the MGH. The data thus far indicated higher local control and disease specific survival after BID radiation therapy for advanced carcinomas (T2-3 lesions). The therapeutic gains, however, did not occur significantly for early lesions (T1 disease). The importance of the effects of the total doses and total treatment time, related to the treatment outcome, is discussed.
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Carcinoma/radioterapia , Neoplasias Laríngeas/radioterapia , Neoplasias Orofaríngeas/radioterapia , Dosificación Radioterapéutica , Análisis Actuarial , Boston , Carcinoma/patología , Supervivencia sin Enfermedad , Hospitales Generales , Humanos , Mucosa Laríngea/efectos de la radiación , Neoplasias Laríngeas/patología , Laringitis/etiología , Recurrencia Local de Neoplasia/prevención & control , Estadificación de Neoplasias , Neoplasias Orofaríngeas/patología , Faringitis/etiología , Radiobiología , Radioterapia de Alta Energía/efectos adversos , Resultado del TratamientoRESUMEN
The study investigated the toxicity and efficiency of the concomitant administration of radiotherapy and carboplatin to patients with head and neck carcinomas. Sixty-three patients with head and neck squamous cell carcinomas, other than nasopharyngeal cancer and Stage I (UICC) laryngeal cancers, were treated by external radiotherapy and four courses of carboplatin at a dose of 100 mg/m2 per week. In two patients, only three courses were possible due to renal toxicity. In the other 61 patients, toxicities were self-limiting and no patient required interruption of carboplatin administration. No patient required discontinuation of radiotherapy because of acute toxicity. Of 61 evaluable patients, a complete response (CR) was obtained in 11.5% and a partial response (PR) in 60.7% at 40 Gy. In 41 patients treated to 65 Gy (including two patients with maxillary sinus carcinoma, who were treated by debulking surgery), CR was obtained in 76.9% and CR+PR was 100% at the end of treatment. The actuarial survival rate of the 63 patients at 2 years was 69.2%, with a median follow-up period of 24.4 months. One of 12 patients who received salvage surgery after radical radiotherapy has died due to poor wound healing after the surgery. The schedule was safe, providing a weekly check of serum samples was possible. It is likely that the rate of local control and vocal cord preservation in laryngeal tumours might improve if concurrent carboplatin is used. Careful follow-up is required to determine the long-term effect of concomitant carboplatin administration.
Asunto(s)
Antineoplásicos/uso terapéutico , Carboplatino/uso terapéutico , Carcinoma de Células Escamosas/terapia , Neoplasias de Cabeza y Cuello/terapia , Traumatismos por Radiación/etiología , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Carboplatino/administración & dosificación , Carboplatino/efectos adversos , Carcinoma de Células Escamosas/mortalidad , Terapia Combinada , Femenino , Neoplasias de Cabeza y Cuello/mortalidad , Humanos , Mucosa Laríngea/efectos de los fármacos , Mucosa Laríngea/patología , Mucosa Laríngea/efectos de la radiación , Masculino , Persona de Mediana Edad , Neoplasias de Oído, Nariz y Garganta/mortalidad , Neoplasias de Oído, Nariz y Garganta/terapia , Pronóstico , Radioterapia Adyuvante/efectos adversos , Terapia Recuperativa , Tasa de SupervivenciaRESUMEN
Between March 1978 and March 1989, 419 patients with 439 moderately advanced or advanced primary squamous cell carcinomas of the head and neck received treatment with curative intent with twice-a-day radiotherapy (120 cGy per fraction with a 4- to 6-hour interfraction interval). Seventy-nine percent of the patients had AJCC stage III or stage IV cancers. The primary site in most patients was the oropharynx, hypopharynx, or larynx. All patients received radiotherapy alone to the primary site, with or without planned neck dissection after radiotherapy. Surgery at the primary site was reserved for salvage of radiotherapy failures. No patient received chemotherapy as part of the initial treatment plan. Total doses were 7440 cGy to 7920 cGy in the majority of patients. In 54 patients with oropharyngeal lesions, an interstitial implant was used to add a 1,000- to 1,500-cGy boost after the basic dose. Local control results were compared on a site-by-site and stage-by-stage basis with the results of continuous-course, once-a-day radiotherapy at the University of Florida; the control results were the same as or better than after once-a-day radiotherapy for each site and stage (T2 to T4). Severe complications of radiotherapy occurred in 4% of patients and correlated with tumor dose, T stage, and disease site (oropharynx or larynx/hypopharynx). The addition of a neck dissection 4 to 6 weeks after radiotherapy of patients with advanced-stage neck disease was accomplished with an acceptable rate of morbidity and significantly improved the rate of control of neck metastases compared with radiotherapy alone.
Asunto(s)
Carcinoma de Células Escamosas/radioterapia , Neoplasias de Cabeza y Cuello/radioterapia , Dosificación Radioterapéutica , Análisis Actuarial , Carcinoma de Células Escamosas/cirugía , Terapia Combinada , Florida , Estudios de Seguimiento , Neoplasias de Cabeza y Cuello/cirugía , Humanos , Neoplasias Hipofaríngeas/radioterapia , Neoplasias Hipofaríngeas/cirugía , Mucosa Laríngea/efectos de la radiación , Neoplasias Laríngeas/radioterapia , Neoplasias Laríngeas/cirugía , Escisión del Ganglio Linfático , Mucosa Bucal/efectos de la radiación , Neoplasias de la Boca/radioterapia , Neoplasias de la Boca/cirugía , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Neoplasias Orofaríngeas/radioterapia , Neoplasias Orofaríngeas/cirugía , Orofaringe/efectos de la radiación , Complicaciones Posoperatorias , Terapia Recuperativa , Tasa de SupervivenciaRESUMEN
Forty-two patients with supraglottic squamous cell carcinoma were irradiated with Co60 using concomitant boost technique, a variant of accelerated fractionation. This technique is characterized by administering the boost as a second daily fraction during the basic wide-field irradiations. Daily dose in the first 4 weeks was 1.8 Gy and during the last 2 weeks it was 1.6 Gy twice daily with 4-6 hours separation. Total dose ranged from 60 to 76 Gy, median 66 Gy. The treatment time ranged from 36 to 56, median 42 days. Acute mucosal reactions were more severe than those of conventional irradiation but acceptable. The follow-up time ranged from 9 to 31 months, median 16 months. The actuarial 18 months survival for all patients was 75%. The actuarial 18 months control for primary site and lymph node was 75% for T1-2 stage, and 47% for T3-4 stage. Severe late complications were not observed so far.
Asunto(s)
Carcinoma de Células Escamosas/radioterapia , Neoplasias Laríngeas/radioterapia , Adulto , Anciano , Radioisótopos de Cobalto/uso terapéutico , Trastornos de Deglución/etiología , Femenino , Estudios de Seguimiento , Humanos , Mucosa Laríngea/efectos de la radiación , Masculino , Persona de Mediana Edad , Proyectos Piloto , Dosificación RadioterapéuticaRESUMEN
Reactions of the laryngeal and neck skin mucosa were studied in 93 laryngeal cancer patients on combined therapy including hyperthermia. Patients in the control groups received no local hyperthermia. Reactions on the laryngeal mucosa (hyperemia, insular and confluent epitheliitis) were observed in all the patients; in patients receiving chemotherapy they were more noticeable. In patients receiving local hyperthermia these reactions appeared somewhat later and were less noticeable and not repeated. Skin reactions correlated only with a radiation dose and did not depend on chemotherapy and hyperthermia. Local electromagnetic hyperthermia in laryngeal cancer patients neither influenced the appearance of radiation reactions nor enhanced them.