RESUMEN
OBJECTIVE: Updated report about the randomized comparison of the effect of radiotherapy on painful osteoarthritis (OA) applying a standard dose vs. a very low dose regime after a follow-up of 1 year. PATIENTS AND METHODS: Patients presenting with OA of the hand/finger and knee joints were included. After randomization (every joint region was randomized separately) the following protocols were applied: (a) standard arm: total dose 3.0â¯Gy, single fractions of 0.5â¯Gy twice a week; (b) experimental arm: total dose 0.3â¯Gy, single fractions of 0.05â¯Gy twice a week. The dosage was blinded for the patients. For evaluation the scores after 1year visual analog scale (VAS), Knee Injury and Osteoarthritis Outcome Score-Short Form (KOOS-PS), Short Form Score for the Assessment and Quantification of Chronic Rheumatic Affections of the Hands (SF-SACRAH) and 12-item Short-Form Health Survey (SF-12) were used (for further details: see [1]). RESULTS: The standard dose was applied to 77 hands and 33 knees, the experimental dose was given to 81 hands and 30 knees. After 12 months, the data of 128 hands and 45 knees were available for evaluation. Even after this long time, we observed a favorable response of pain to radiotherapy in both trial arms; however, there were no reasonable statistically significant differences between both arms concerning pain, functional, and quality of life scores. Side effects did not occur. The only prognostic factor was the pain level before radiotherapy. CONCLUSIONS: We found a favorable pain relief and a limited response in the functional and quality of life scores in both treatment arms. The possible effect of low doses such as 0.3â¯Gy on pain is widely unknown.
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Osteoartritis de la Rodilla , Osteoartritis , Humanos , Estudios de Seguimiento , Calidad de Vida , Osteoartritis/radioterapia , Dolor/radioterapia , Manejo del Dolor , Osteoartritis de la Rodilla/radioterapia , Resultado del TratamientoRESUMEN
PURPOSE: Randomized comparison of the effect of radiotherapy on painful osteoarthritis (OA) applying a standard-dose vs. a very-low-dose regime PATIENTS AND METHODS: Patients with OA of the hand and knee joints were included. Further inclusion criteria: symptoms for more than 3 months, favorable general health status, age above 40 years. Patients with prior local radiotherapy, trauma, rheumatoid arthritis, or vascular diseases were excluded. After randomization (every joint was randomized separately), the following protocols were applied: standard arm: total dose 3.0â¯Gy, single fractions of 0.5â¯Gy twice weekly; experimental arm: total dose 0.3â¯Gy, single fractions of 0.05â¯Gy twice weekly. The dosage was not known to the patients. The patients were examined 3 and 12 months after radiotherapy. Scores like VAS (visual analogue scale), KOOS-SF (the knee injugy and osteoarthritis outcome score), SF-SACRAH (short form score for the assessment and quantification of chronic rheumatic affections of the hands), and SF-12 (short form 12) were used. RESULTS: A total of 64 knees and 172 hands were randomized. 3.0â¯Gy was applied to 87 hands and 34 knees, 0.3â¯Gy was given to 85 hands and 30 knees. After 3 months, we observed good pain relief after 3â¯Gy and after 0.3â¯Gy, there was no statistically significant difference. Side effects were not recorded. The trial was closed prematurely due to slow recruitment. CONCLUSION: We found favorable pain relief and a limited response in the functional and quality of life scores in both arms. The effect of low doses such as 0.3â¯Gy on pain is widely unknown. Further trials are necessary to compare a conventional dose to placebo and to further explore the effect of low doses on inflammatory disorders.
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Osteoartritis de la Rodilla , Osteoartritis , Adulto , Estudios de Seguimiento , Humanos , Osteoartritis/radioterapia , Osteoartritis de la Rodilla/radioterapia , Dolor/radioterapia , Estudios Prospectivos , Calidad de Vida , Resultado del TratamientoRESUMEN
PURPOSE: Treatment of patients with laryngeal squamous cell carcinoma with radiotherapy or chemoradiation is an established alternative to laryngeal surgery in many cases, but particularly for advanced tumors without cartilage invasion. Imaging modalities face the challenge of distinguishing between posttherapeutic changes and residual disease in the complex anatomic subsite of the larynx. Guidelines concerning restaging of head and neck squamous cell carcinomas (HNSCC) are presented by the National Comprehensive Cancer Network (NCCN) and other national guidelines, but clearly defined recommendations for routine restaging particularly for laryngeal cancer are lacking. METHODS: A systematic search was carried out in PubMed to identify studies evaluating routine restaging methods after primary non-surgical treatment of laryngeal squamous cell carcinoma from 2009 to 2020. RESULTS: Only three studies were deemed eligible, as they included at least ≥50% patients with laryngeal squamous cell carcinoma and evaluated imaging modalities to detect residual cancer. The small number of studies in our review suggest restaging with fluoro-deoxy-glucose positron-emission tomography/computed tomography (FDG PET/CT) 3 months after initial treatment, followed by direct laryngoscopy with biopsy of the lesions identified by FDG PET/CT. CONCLUSION: Studies evaluating restaging methods after organ-preserving non-surgical treatment of laryngeal carcinoma are limited. As radiotherapy (RT), chemoradiotherapy (CRT), systemic therapy followed by RT and radioimmunotherapy are established alternatives to surgical treatment, particularly in advanced laryngeal cancers, further studies are needed to assess and compare different imaging modalities (e.g. PET/CT, MRI, CT, ultrasound) and clinical diagnostic tools (e.g., video laryngoscopy, direct laryngoscopy) to offer patients safe and efficient restaging strategies. PET or PET/CT 3 months after initial treatment followed by direct laryngoscopy with biopsy of the identified lesions has the potential to reduce the number of unnecessary laryngoscopies.
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Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/terapia , Neoplasias Laríngeas/patología , Neoplasias Laríngeas/terapia , Laringe/patología , Biopsia/métodos , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/radioterapia , Quimioradioterapia , Fluorodesoxiglucosa F18/análisis , Humanos , Neoplasias Laríngeas/tratamiento farmacológico , Neoplasias Laríngeas/radioterapia , Laringoscopía/métodos , Laringe/efectos de los fármacos , Laringe/efectos de la radiación , Estadificación de Neoplasias/métodos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodosRESUMEN
PURPOSE: Osteoarthritis of the ankle and tarsal joints is less common than osteoarthritis of the knee or hip, but the associated disability is at least as severe as that of the other major joints of the lower limb. The results for total arthroplasty are still not satisfactory. For this reason, arthrodesis is still the gold standard of non-joint-conserving surgery. For the reason of functionality, joint-conserving therapies play a major role in treatment of ankle and tarsal osteoarthritis. Low-dose radiotherapy has a long history of treatment of osteoarthritis. The aim of this survey was to examine the results of low-dose radiotherapy for osteoarthritis of the ankle and tarsal joints. MATERIALS AND METHODS: The analysis was performed on patients of three German radiotherapy institutions and included 66 irradiated joints. Pain was documented with the numeric rating scale (NRS). Evaluation of the NRS was done before and directly after each radiation therapy course as well as for the follow-up of 24 months. The median age of the patients was 68 years, with 24.5% male and 75.5% female patients. The upper ankle was treated in 37.9%, the lower ankle in 27.3% and the tarsal joints in 34.8%. RESULTS: We could find a significant response to radiotherapy. For the whole sample, the median pain was 7 on the NRS before radiotherapy, 5 after 6 and 12 weeks, and 4 after 12 months. The percentage of patients with 0 or 1 on the NRS was 19.6% 12 months after radiotherapy. An improvement of joint mobility could be detected in 56.7% of the cases. All investigated subgroups had a significant reduction in pain. CONCLUSION: Radiotherapy of ankle and tarsal osteoarthritis is an effective treatment without showing side effects. All analysed subgroups show a good response to radiotherapy for at least 24 months.
Asunto(s)
Articulación del Tobillo/efectos de la radiación , Osteoartritis/radioterapia , Articulaciones Tarsianas/efectos de la radiación , Anciano , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Recuperación de la Función , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Humeral epicondylitis is a common elbow disease. The prevalence is about 1.7%. One of the most effective treatment options is radiotherapy. Some authors mention that they apply a second or third course of radiation for recurrent pain or partial or no response to the initial course. As the results of a re-irradiation have not been systematically analyzed, the aim of this study was to document the results of repeated radiation treatment and to identify those patients who will benefit. MATERIAL AND METHODS: The analysis was performed on patients from three German radiotherapy institutions and included 99 re-irradiated elbows. Pain was documented with the numeric rating scale (NRS). Evaluation of the NRS was done before and directly after each radiation therapy as well as for the follow-up of 24 months. The median age of the patients was 51 years with 48.8% male and 51.2% female patients. Repeated radiation was indicated because the initial radiotherapy resulted in 39.7% of no response, in 41.0% of partial response and in 19.3% of recurrent pain. RESULTS: A significant response to re-irradiation was found. For the whole sample the median pain score was 6 before re-irradiation, 3 after 6 weeks, 2 after 12 months and 1 after 24 months. The percentage of patients being free of pain or with very little pain was 50.9% 24 months after re-irradiation. All subgroups, notably those with no response, partial response and recurrent pain had a significant reduction of pain. CONCLUSION: Re-irradiation of humeral epicondylitis is an effective and safe treatment. All subgroups showed a good response to re-irradiation for at least 24 months.
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Codo/efectos de la radiación , Codo de Tenista/radioterapia , Femenino , Estudios de Seguimiento , Humanos , Húmero/efectos de la radiación , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Reirradiación , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
PURPOSE: Osteoarthritis is a common disease, with a prevalence of symptomatic disease of 8.9%. One treatment option is radiotherapy. Most published samples were treated with an orthovoltage technique or with a telecobalt device. A lot of radiotherapy institutions are nowadays using linear accelerators for treatment of osteoarthritis. There is a discussion on whether the treatment results achieved with a linear accelerator are comparable to those with the orthovoltage technique. The aim of this study is to analyze the results of radiotherapy for osteoarthritis with a linear accelerator and compare the results with reference to different joints. MATERIALS AND METHODS: The analysis was performed in patients of two German radiotherapy institutions and included 295 irradiated joints. Pain was documented with the numeric rating scale (NRS). Evaluation of the NRS was done before and directly after each radiation therapy course as well as for the follow-up of 24 months. The median age of the patients was 65 years, with 39.0% male and 61.0% female patients. Most frequently, osteoarthritis of the knee (34.6%) or the finger (15.9%) was treated. RESULTS: We could find a significant response to radiotherapy. Median pain for the whole sample was 7 on the NRS before radiotherapy, 4 after 6 weeks, and 3 after 12 and 24 months. The percentage of patients with 0 or 1 on the NRS was 33.8% 12 months after radiotherapy. All investigated subgroups had a significant reduction of pain. CONCLUSION: Radiotherapy of osteoarthritis with a linear accelerator is an effective treatment which is very well tolerated. All analyzed subgroups show a good response to radiotherapy for at least 24 months. Orthovoltage therapy seems to be superior to treatment with a linear accelerator in a case-related analysis of the published samples. Further investigations should be performed for a definitive answer to this question.
Asunto(s)
Osteoartritis/radioterapia , Aceleradores de Partículas , Anciano , Anciano de 80 o más Años , Fraccionamiento de la Dosis de Radiación , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Especificidad de Órganos , Osteoartritis de la Rodilla/radioterapia , Dimensión del Dolor , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Head and neck squamous cell cancer (HNSCC) frequently causes severe symptoms that may be reduced, when the tumor is successfully treated. The SOCCER trial studied the association of treatment response with patient reported tumor symptom burden in first line treatment of recurrent and/or metastatic HNSCC. METHODS: In this prospective, multi-center, non-interventional trial patients were treated either with platinum-based chemotherapy and cetuximab or radiotherapy and cetuximab. Tumor symptom burden was assessed every four weeks with a questionnaire containing ten visual analogue scales (VAS, range 0-100), which were summarized to the overall VAS score. RESULTS: Fourhundred seventy patients were registered in 97 German centers. A total of 315 patients with at least the baseline and one subsequent questionnaire were available for analysis. Changes in the VAS score were rated as absolute differences from baseline. Negative values indicate improvement of symptoms. The overall VAS score improved significantly at the first post-baseline assessment in responders (- 2.13 vs. non-responders + 1.15, p = 0.048), and even more for the best post-baseline assessment (- 7.82 vs. non-responders - 1.97, p = 0.0005). The VAS for pain (- 16.37 vs. non-responders - 8.89, p = 0.001) and swallowing of solid food (- 16.67 vs. non-responders - 5.06, p = 0.002) improved significantly more in responders (best post-baseline assessment). In the multivariable Cox regression analysis, worse overall VAS scores were associated with worse overall survival (hazard ratio for death 1.12 per 10 points increment on the overall VAS scale, 95% CI 1.05-1.20, p = 0.0009). CONCLUSION: In unselected patients beyond randomized controlled trials, treatment response lowers tumor symptom burden in recurrent and/or metastatic HNSCC. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00122460 . Registered 22 Juli 2005.
Asunto(s)
Cetuximab/administración & dosificación , Recurrencia Local de Neoplasia/tratamiento farmacológico , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Carcinoma de Células Escamosas de Cabeza y Cuello/radioterapia , Adulto , Anciano , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Cetuximab/efectos adversos , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Terapia Combinada , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/radioterapia , Platino (Metal)/administración & dosificación , Platino (Metal)/efectos adversos , Supervivencia sin Progresión , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Carcinoma de Células Escamosas de Cabeza y Cuello/patologíaRESUMEN
Tumor immune microenvironment and tumor metabolism are major determinants of chemoradiotherapy response. The interdependency and prognostic significance of specific immune and metabolic phenotypes in head and neck squamous cell carcinoma (HNSCC) were assessed and changes in reactive oxygen species were evaluated as a mechanism of treatment response in tumor spheroid/immunocyte co-cultures. Pretreatment tumor biopsies were immunohistochemically characterized in 73 HNSCC patients treated by definitive chemoradiotherapy and correlated with survival. The prognostic significance of CD8A, GLUT1, and COX5B gene expression was analyzed within The Cancer Genome Atlas database. HNSCC spheroids were co-cultured in vitro with peripheral blood mononuclear cells (PBMCs) in the presence of the glycolysis inhibitor 2-deoxyglucose and radiation treatment followed by PBMC chemotaxis determination via fluorescence microscopy. In the chemoradiotherapy-treated HNSCC cohort, mitochondrial-rich (COX5B) metabolism correlated with increased and glucose-dependent (GLUT1) metabolism with decreased intratumoral CD8/CD4 ratios. High CD8/CD4, together with mitochondrial-rich or glucose-independent metabolism, was associated with improved short-term survival. The Cancer Genome Atlas analysis confirmed that patients with a favorable immune and metabolic gene signature (high CD8A, high COX5B, low GLUT1) had improved short- and long-term survival. In vitro, 2-deoxyglucose and radiation synergistically up-regulated reactive oxygen species-dependent PBMC chemotaxis to HNSCC spheroids. These results suggest that glucose-independent tumor metabolism is associated with CD8-dominant antitumor immune infiltrate, and together, these contribute to improved chemoradiotherapy response in HNSCC.
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Antineoplásicos/uso terapéutico , Carcinoma de Células Escamosas/terapia , Quimioradioterapia , Neoplasias de Cabeza y Cuello/terapia , Anciano , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Antígenos CD8/genética , Antígenos CD8/metabolismo , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/mortalidad , Línea Celular Tumoral , Grupo Citocromo c/genética , Grupo Citocromo c/metabolismo , Bases de Datos Genéticas , Complejo IV de Transporte de Electrones , Femenino , Transportador de Glucosa de Tipo 1/genética , Transportador de Glucosa de Tipo 1/metabolismo , Neoplasias de Cabeza y Cuello/metabolismo , Neoplasias de Cabeza y Cuello/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Especies Reactivas de Oxígeno/metabolismo , Tasa de SupervivenciaRESUMEN
PURPOSE: Ionizing radiation is able to cause severe damage to cardiac implantable electronic devices (CIED). In Germany, the DEGRO/DGK guideline recommends close monitoring of patients with CIEDs undergoing radiotherapy (RT). Nevertheless, especially in the era of intensity-modulated techniques and predominant use of 6â¯MV photons, errors of CIEDs are rare events. Therefore, we performed daily CIED controls and hypothesized that no relevant device interaction would occur in our cohort. METHODS: From 2014 to 2018, we collected data of 51 patients (62 courses) with daily interrogation (nâ¯= 1046) of CIED. The dose to the skin above the CIED was measured by semiconductor or ion chamber dosimetry at least once per RT course. In many cases the dose was also calculated. RESULTS: The prescribed dose to the planning target volume (PTV) ranged from 7.5 to 78.0â¯Gy (IQR 27.8-61.0â¯Gy). The median measured cumulative dose to the skin above the CIED was 0.17â¯Gy, whereas the median calculated dose was 1.03â¯Gy. No error occurred in the group with maximum beam energy >10â¯MeV. Three events without clinical relevance could be recognized in the group with an intensity-modulated technique at 6â¯MV. None of the three concerned devices were located directly within the PTV. CONCLUSION: Errors of CIEDs during RT are rare events. The approach according to the DEGRO/DGK guideline is safe, but also consumes resources. In our cohort it was not compulsory to relocate any CIED. Clinically relevant events are uncommon, so it remains debatable which procedure is necessary. Daily controls could be avoided in some selected cases without compromising patient safety.
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Contraindicaciones de los Procedimientos , Desfibriladores Implantables , Adhesión a Directriz , Marcapaso Artificial , Radioterapia/efectos adversos , Medición de Riesgo , Estudios de Cohortes , Correlación de Datos , Relación Dosis-Respuesta en la Radiación , Análisis de Falla de Equipo/estadística & datos numéricos , Neoplasias de Cabeza y Cuello/radioterapia , Humanos , Incidencia , Neoplasias Pulmonares/radioterapia , Análisis de Activación de Neutrones , Radioterapia/estadística & datos numéricos , Estudios Retrospectivos , Medición de Riesgo/estadística & datos numéricos , Estadística como AsuntoRESUMEN
PURPOSE: Osteoarthritis is a common disease with a prevalence of approximately 8.9% among the average population. One treatment option is low-dose radiotherapy. Some authors mention that they apply a second or third course of radiation for recurrent pain or partial or no response to the initial course. As the results of re-irradiation have not been analysed systematically, the aim of this study was to document the results of repeated radiation treatment and to identify those patients who will benefit. METHODS AND MATERIALS: The analysis was performed on patients of three German radiotherapy institutions and included 217 re-irradiated joints. Pain was documented with the numeric rating scale (NRS). Evaluation of the NRS was done before and directly after each radiation therapy as well as at the follow-up of 24 months. The median age of the patients was 67 years, with 40% male and 60% female patients. Re-irradiation was indicated because the initial radiotherapy resulted in no response in 21.2%, in partial response in 41.5%, and in recurrent pain in 37.3%. RESULTS: We found a significant response to re-irradiation. For the whole sample, the median pain was 6 before re-irradiation, 4 after 6 weeks, and 3 after 12 weeks, 6 months, 12 months, and 24 months. The percentage of patients being free of pain or with very little pain was approximately 25% 12 months after re-irradiation. All subgroups, notably those with no response to the first course versus partial response to the first course versus recurrent pain, had significant reduction of pain. CONCLUSION: Re-irradiation of osteoarthritis is an effective and safe treatment. All subgroups showed a good response to re-irradiation for at least 24 months.
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Osteoartritis/radioterapia , Reirradiación/métodos , Anciano , Terapia Combinada , Femenino , Estudios de Seguimiento , Alemania , Humanos , Articulaciones/efectos de la radiación , Articulaciones/cirugía , Masculino , Persona de Mediana Edad , Osteoartritis/cirugía , Dimensión del Dolor , Dosificación Radioterapéutica , Radioterapia Adyuvante/métodos , Estudios RetrospectivosRESUMEN
BACKGROUND: Epicondylitis humeri is a common disease with a prevalence of 1.7%. One of the treatment options is radiotherapy. Most published cases were treated with the orthovoltage technique or with a telecobalt device. Many radiotherapy institutions are nowadays using linear accelerators for treatment of epicondylitis humeri. There is a discussion whether the treatment results with linear accelerators are comparable to the orthovoltage technique. The aim of this study was to analyze the results of radiotherapy with a linear accelerator for epicondylitis humeri. MATERIAL AND METHODS: The analysis was performed on patients of 2 German radiotherapy institutions and included 138 irradiated elbows. Pain was documented with the numeric rating scale (NRS). Evaluation of the NRS was done before and directly after each radiation therapy course as well as for the follow-up of 24 months. The median age of the patients was 49 years with 48.4% male and 51.6% female. In all, 81.0% were suffering from from epicondylitis humeri radialis while 16.7% were treated because of epicondylitis humeri ulnaris. In 65.4% the dominant arm was treated. RESULTS: A significant response to radiotherapy could be found. For the whole sample the median pain was 7 on the NRS before radiotherapy, 4 after 6 weeks and 0 after 12 and 24 months. The percentage of patients with 0 or 1 on the NRS was 64.6% 12 months after radiotherapy. All subgroups, notably those with epicondylitis humeri radialis and epicondylitis humeri ulnaris had a significant reduction of pain. CONCLUSION: Radiotherapy of epicondylitis humeri with a linear accelerator is an effective treatment without showing side effects. All analyzed subgroups showed a good response to radiotherapy for at least 24 months.
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Aceleradores de Partículas , Codo de Tenista/radioterapia , Adulto , Anciano , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
PURPOSE: Osteoarthritis of the knee is a common disease, often associated with a Baker's cyst. Besides osteoarthritis, also other joint pathologies of the knee can be causative for a Baker's cyst. Radiotherapy is known to be an effective treatment for osteoarthritis, with an anti-inflammatory effect. As the excessive production of synovia usually is associated with intraarticular inflammation, our hypothesis was that radiotherapy might positively influence the synovial production and reduce the volume of a Baker's cyst. MATERIALS AND METHODS: We performed a prospective trial, including 20 knees receiving radiotherapy for knee arthritis. Besides documentation of NRS (numeric rating scale), WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) score and Knee Society Score, the volume of the Baker's cyst was calculated for a short- (6 to 12 weeks) and long-term (9 to 12 months) follow-up. Ultrasonic volumetry was performed using an ultrasound device with a high-resolution multifrequency linear probe (6-9â¯MHz). RESULTS: Low-dose radiotherapy improved NRS, WOMAC score and Knee Society Score significantly. The mean volume of Baker's cyst decreased from 22.3â¯ml to 10.7 respectively 3.1â¯ml during follow-up. A decrease in volume of more than 25% compared to the baseline could be achieved for 75% of the patients in the short-term and 79% of the patients in the long-term follow up. CONCLUSION: Radiotherapy of knee osteoarthritis is an effective treatment that decreases the volume of a Baker's cyst. Most patients respond to the treatment. Whether radiotherapy is an effective treatment for Baker's cyst without associated osteoarthritis has to be further examined.
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Osteoartritis de la Rodilla/radioterapia , Quiste Poplíteo/radioterapia , Dosificación Radioterapéutica , Anciano , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Osteoartritis de la Rodilla/diagnóstico por imagen , Quiste Poplíteo/diagnóstico por imagen , Estudios Prospectivos , Resultado del Tratamiento , Ultrasonografía/métodosRESUMEN
OBJECTIVES: The aim of this study is to investigate the influence of prognostic biomarkers on radiosensitivity and survival of advanced head and neck squamous cell carcinomas treated by primary (chemo)radiation. MATERIAL AND METHODS: The clinicopathological data and immunohistochemical staining of p16, c-Met, survivin, PD-1, and PD-L1 of 82 primarily (chemo)irradiated patients with head and neck squamous cell carcinoma were analyzed. Associations with local and locoregional radiation response, overall survival (OS), disease-free (DFS), and disease-specific survival (DSS) were assessed. RESULTS: Complete tumor response was associated with increased patient age (p = 0.007), N0-status (p = 0.022), M0-status (p = 0.007), and p16-positivity (p = 0.022). High PD-L1 was associated with M0-status (p = 0.026) and indicated tumor response to irradiation (p = 0.057); survivin expression showed higher rates of response failure (p = 0.073). Low PD-1 was associated with increased T-stage (p = 0.029) and local recurrence (p = 0.014). High PD-1 was strongly correlated with PD-L1-positive tumor infiltrating lymphocytes (p < 0.001). Low PD-L1 showed a significant correlation with high c-Met expression (p = 0.01). Significant predictors for unfavorable univariate survival were incomplete tumor response (DSS, p < 0.001), single radiotherapy (DSS, p = 0.002), M1-status (DSS, p < 0.001), decreased radiation dose (DSS, p = 0.014), high survivin (DSS, p = 0.045), and high c-Met (OS, p < 0.05). Survivin and c-Met also showed prognostic significance in multivariate survival analysis. CONCLUSIONS: P16 and PD-L1 indicate radiosensitivity, whereas survivin and c-Met implicate radioresistance in primarily (chemo)irradiated head and neck squamous cell carcinomas. The role of the PD-1/PD-L1 immune checkpoints in radiation response and survival merits further investigation. CLINICAL RELEVANCE: The findings may improve patient-specific therapy according to individual tumor characteristics.
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Biomarcadores de Tumor/análisis , Carcinoma de Células Escamosas/radioterapia , Neoplasias de Cabeza y Cuello/radioterapia , Tolerancia a Radiación/fisiología , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/patología , Femenino , Neoplasias de Cabeza y Cuello/patología , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Pronóstico , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: Cetuximab (CET) is a potent inhibitor of the epidermal growth factor receptor and has been shown to have activity in squamous cell carcinoma of the head and neck (SCCHN). We conducted a single-arm phase II trial of a combination therapy comprising cisplatin (CIS), CET and hyperfractionated accelerated radiotherapy (HART). PATIENTS AND METHODS: Patients with UICC stage III or IVA/B, M0 SCCHN were enrolled and treated with an initial dose of CET (400 mg/m2) and then with a weekly dosage of 250 mg/m2 during HART. HART was started with a prescribed dosage of 2.0 Gy per day for 3 weeks, followed by 1.4 Gy twice daily to a total dose of 70.6 Gy to the gross tumour volume. CIS (40 mg/m2) was administered weekly (days 1, 8, 15, 22, 29 and 36). The primary objective of the phase II study was to determine the 2year progression-free survival (PFS). RESULTS: Between November 2007 and November 2010, a total of 74 patients were enrolled in the study, of whom 65 were evaluable (83% were men). Median age was 56 years (range 37-69 years). An Oropharyngeal primary tumour was diagnosed in 49%, T4a,b in 65% and N2/3 in 96% of the patients. Of these patients, 85% were smokers or ex-smokers. Complete remission (CR) was observed in 23 patients (35%). The most common toxicity grade was ≥3, including mucositis (58%) and dysphagia (52%). The 2 and 5year overall survival rates were 64 and 41%, the 2 and 5year PFS rates were 45 and 32%, and the 2 and 5year locoregional control rates were 47 and 33%, respectively. CONCLUSION: The combination of weekly CIS with HART plus CET is a feasible regimen for these unfavourable smoking-induced cancers. However, the parallel US study (RTOG 0522) showed no advantage of the enhanced triple therapy compared to chemoradiotherapy alone.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/terapia , Cetuximab/administración & dosificación , Cisplatino/administración & dosificación , Fraccionamiento de la Dosis de Radiación , Neoplasias Orofaríngeas/patología , Neoplasias Orofaríngeas/terapia , Neoplasias de Oído, Nariz y Garganta/patología , Neoplasias de Oído, Nariz y Garganta/terapia , Adulto , Anciano , Carcinoma de Células Escamosas/mortalidad , Terapia Combinada , Supervivencia sin Enfermedad , Esquema de Medicación , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Orofaríngeas/mortalidad , Neoplasias de Oído, Nariz y Garganta/mortalidad , Dosificación Radioterapéutica , Fumar/efectos adversosRESUMEN
BACKGROUND: In this randomized multicenter trial, we compared the effect of a lower single dose of 0.5 Gy vs. a standard single dose of 1 Gy concerning pain relief and quality of life, while maintaining a uniform total dose of 6 Gy. On the basis of laboratory observations, the lower single dose would be expected to be more effective. PATIENTS AND METHODS: A total of 127 patients suffering from painful heel spur were randomized: Patients in the standard group were treated with single fractions of 6 × 1 Gy twice a week, while the experimental group was treated with single fractions of 12 × 0.5 Gy three times a week. Patients who did not show satisfactory pain relief after 12 weeks were offered re-irradiation with the standard dose. The study's primary endpoints were pain relief and quality of life. Therapy results were evaluated and compared based on follow-up examinations after 12 and 48 weeks. RESULTS: The data of 117 patients could be evaluated. There was no significant difference between the groups concerning the results of a visual analogue scale (VAS), Calcaneodynia Score (CS), and the somatic scale of the 12-Item Short-Form Health Survey(SF-12). Patients undergoing re-irradiation showed a significant benefit concerning pain relief. Their total outcome was comparable to patients showing a good response from the beginning. No relevant acute or chronic side effects were recorded. CONCLUSION: Both patient groups showed good results concerning pain relief. A fractionation schedule of 12 × 0.5 Gy was not superior to the current standard dose of 6 × 1 Gy. Further trials are necessary to explore the best fractionation schedule.
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Fraccionamiento de la Dosis de Radiación , Espolón Calcáneo/radioterapia , Dolor/radioterapia , Adulto , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Dolor/psicología , Dimensión del Dolor/efectos de la radiación , Aceleradores de Partículas , Calidad de Vida/psicología , Dosificación RadioterapéuticaRESUMEN
Tumor-induced osteomalacia (TIO) is a paraneoplastic syndrome resulting in renal phosphate wasting and decreased bone mineralization. TIO is usually induced by small, slowly growing tumors of mesenchymal origin (phosphaturic mesenchymal tumor mixed connective tissue variant [PMTMCT]). Nonspecific symptoms including fatigue, bone pain, and musculoskeletal weakness make the diagnosis elusive and often lead to a delay in treatment. The prognosis of TIO is excellent following complete resection of the neoplasm, which leads to the rapid and complete reversal of all symptoms. If the tumor cannot be detected, treatment relies on supplementation with phosphate and active vitamin D compounds. Subsequent radiotherapy in case of incompletely resected tumors or definitive radiotherapy in unresectable tumors is an important treatment option to avoid recurrence or metastasis even though this occurs rarely. Due to the risk of recurrence or late metastases, long-term monitoring is required even in TIO patients diagnosed with a benign tumor.
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Neoplasias de Tejido Conjuntivo/etiología , Síndromes Paraneoplásicos/etiología , Diagnóstico Diferencial , Humanos , Mesenquimoma/complicaciones , Mesenquimoma/terapia , Neoplasias de Tejido Conjuntivo/complicaciones , Neoplasias de Tejido Conjuntivo/diagnóstico , Neoplasias de Tejido Conjuntivo/terapia , Osteomalacia , Síndromes Paraneoplásicos/diagnóstico , Síndromes Paraneoplásicos/terapia , PronósticoRESUMEN
BACKGROUND: Many cancer patients receive a central venous catheter or port system prior to therapy to assure correct drug administration. Even appropriate hygienic intervention maintenance carries the risk of contaminating the middle port (C-port) of a three-way cock (TWC), a risk that increases with the number of medical interventions. Because of the complexity of the cleaning procedure with disconnection and reconnection of the standard luer lock cap (referred as "intervention"), we compared luer lock caps with a "closed access system" consisting of a luer access split septum system with regard to process optimization (work simplification, process time), efficiency (costs) and hygiene (patient safety). METHODS: For determination of process optimization the workflow of an intervention according to the usual practice and risks was depicted in a process diagram. For determining the actual process costs, we analyzed use of material and time parameters per intervention and used the process parameters for programming the process into a simulation run (n = 1000) to determine the process costs as well as their differences (ACTUAL vs. NOMINAL) within the framework of a discrete event simulation.Additionally cultures were carried out at the TWC C-ports to evaluate possible contamination. RESULTS: With the closed access system, the mean working time of 5.5 minutes could be reduced to 2.97 minutes. The results for average process costs (labour and material costs per use) were 3.92 for luer lock caps and 2.55 for the closed access system. The hypothesis test (2-sample t-test, CI 0.95, p-value<0.05) confirmed the significance of the result.In 50 reviewed samples (TWC's), the contamination rate for the luer lock cap was 8% (4 out of 50 samples were positive), the contamination rate of the 50 samples with the closed access system was 0%.Possible hygienic risks (related to material, surroundings, staff handling) could be reduced by 65.38%. CONCLUSIONS: In the present research, the closed access system with a divided split septum was superior to conventional luer lock caps. The advantage of the closed access system lies in the simplified handling for staff, which results in a reduced risk of patient infection due to improved clinical hygiene.
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Cateterismo Venoso Central/efectos adversos , Catéteres de Permanencia/efectos adversos , Catéteres Venosos Centrales/efectos adversos , Infecciones/transmisión , Seguridad del Paciente , Adulto , Cateterismo Venoso Central/instrumentación , Catéteres de Permanencia/economía , Catéteres de Permanencia/microbiología , Catéteres Venosos Centrales/economía , Catéteres Venosos Centrales/microbiología , Costos y Análisis de Costo , Humanos , Higiene , Infecciones/etiología , Riesgo , Simplificación del TrabajoRESUMEN
PURPOSE: Individual prediction of treatment response is crucial for personalized treatment in multimodal approaches against head-and-neck squamous cell carcinoma (HNSCC). So far, no reliable predictive parameters for treatment schemes containing immunotherapy have been identified. This study aims to predict treatment response to induction chemo-immunotherapy based on the peripheral blood immune status in patients with locally advanced HNSCC. METHODS: The peripheral blood immune phenotype was assessed in whole blood samples in patients treated in the phase II CheckRad-CD8 trial as part of the pre-planned translational research program. Blood samples were analyzed by multicolor flow cytometry before (T1) and after (T2) induction chemo-immunotherapy with cisplatin/docetaxel/durvalumab/tremelimumab. Machine Learning techniques were used to predict pathological complete response (pCR) after induction therapy. RESULTS: The tested classifier methods (LDA, SVM, LR, RF, DT, and XGBoost) allowed a distinct prediction of pCR. Highest accuracy was achieved with a low number of features represented as principal components. Immune parameters obtained from the absolute difference (lT2-T1l) allowed the best prediction of pCR. In general, less than 30 parameters and at most 10 principal components were needed for highly accurate predictions. Across several datasets, cells of the innate immune system such as polymorphonuclear cells, monocytes, and plasmacytoid dendritic cells are most prominent. CONCLUSIONS: Our analyses imply that alterations of the innate immune cell distribution in the peripheral blood following induction chemo-immuno-therapy is highly predictive for pCR in HNSCC.
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Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/genética , Quimioterapia de Inducción/métodos , Inmunofenotipificación , Inmunoterapia , Linfocitos T CD8-positivos , Inmunidad InnataRESUMEN
Most of the patients with head and neck squamous cell carcinoma (HNSCC) are diagnosed with locally advanced disease. Standards of care for curative-intent treatment of this patient group are either surgery and adjuvant radio(chemo)therapy (aRCT) or definitive chemoradiation. Despite these treatments, especially pathologically intermediate and high-risk HNSCC often recur. The ADRISK trial investigates in locally advanced HNSCC and intermediate and high risk after up-front surgery if the addition of pembrolizumab to aRCT with cisplatin improves event-free sur-vival compared to aRCT alone. ADRISK is a prospective, randomized controlled investiga-tor-initiated (IIT)-phase II multicenter trial within the German Interdisciplinary Study Group of German Cancer Society (IAG-KHT). Patients with primary resectable stage III and IV HNSCC of the oral cavity, oropharynx, hypopharynx and larynx with pathologic high (R1, extracapsular nodal extension) or intermediate risk (R0 <5 mm; N≥2) after surgery will be eligible. Two hun-dred forty patients will be randomly assigned (1:1) to either standard aRCT with cisplatin (standard arm) or aRCT with cisplatin + pembrolizumab (200 mg iv, in 3-week cycle, max. 12 months) (interventional arm). Endpoints are event-free and overall survival. Recruitment started in August 2018 and is ongoing.