Recomendaciones para el seguimiento de niños con asimetría en la longitud de los miembros inferiores: consenso de expertos / Recommendations for the follow-up of children with leg length discrepancy: expert consensus

La asimetría de la longitud de los miembros inferiores es una afección en la cual la longitud de una pierna difiere de la contralateral, motivo de consulta frecuente en el consultorio del pediatra y del ortopedista infantil. El objetivo de nuestro trabajo fue desarrollar recomendaciones de seguimiento, planificación prequirúrgica y tratamiento de niños con asimetría de la longitud de los miembros inferiores mediante el consenso de expertos. Material y métodos. Se utilizó el método Delphi. Un grupo coordinador seleccionó el panel de expertos, diseñó y analizó cada una de las rondas de consulta. Los cuestionarios semiestructurados fueron enviados por correo electrónico en forma personalizada. Se estableció como criterio de consenso un acuerdo entre los expertos > 80 %. En cada una de las rondas, se reformularon los aspectos no consensuados y se agregaron nuevos sugeridos en la ronda anterior. Se consideró como medida de estabilidad para concluir la consulta cuando más del 70 % de los expertos no modificó su opinión en rondas sucesivas. Resultados. Participaron del consenso 8 expertos en ortopedia y 6 en diagnóstico por imágenes. Luego de 3 rondas de consulta, se logró el consenso en 39 recomendaciones referentes a seguimiento, planificación prequirúrgica y tratamiento. Fueron reagrupadas en 32 recomendaciones finales. Conclusiones. Estas son las primeras recomendaciones para el seguimiento de niños con asimetría de la longitud de los miembros inferiores mediante el consenso de expertos.

Leg length discrepancy is when the length of one leg is different from the other, and is a common reason for consultation at the pediatrician's and pediatric orthopedist's office. The objective of this study was to develop recommendations for the follow-up, pre-surgical planning, and treatment of children with leg length discrepancy based on expert consensus. Material and methods. The Delphi method was used. A coordinating group selected a panel of experts, designed and analyzed each of the rounds of consultations. Semistructured questionnaires were sent by personalized e-mail. Agreement among experts ≥ 80 % was established as the criterion for consensus. At each round of consultation, non-consensual aspects were reformulated and new aspects suggested in the previous round were included. A measure of stability to conclude the consultation was determined when more than 70 % of experts sustained their opinion in successive rounds. Results. Eight experts in orthopedics and six experts in imaging studies participated. After three rounds of consultations, consensus was reached in terms of 39 recommendations for follow-up, pre-surgical planning, and treatment. These were reorganized into 32 final recommendations. Conclusions. These are the first recommendations for the follow-up of children with leg length discrepancy agreed by expert consensus.

Recommendations for the follow-up of children with leg length discrepancy: expert consensus. / Recomendaciones para el seguimiento de niños con asimetría en la longitud de los miembros inferiores: consenso de expertos.

INTRODUCTION: Leg length discrepancy is when the length of one leg is different from the other, and is a common reason for consultation at the pediatrician's and pediatric orthopedist's office. The objective of this study was to develop recommendations for the follow-up, pre-surgical planning, and treatment of children with leg length discrepancy based on expert consensus. MATERIAL AND METHODS: The Delphi method was used. A coordinating group selected a panel of experts, designed and analyzed each of the rounds of consultations. Semistructured questionnaires were sent by personalized e-mail. Agreement among experts > 80 % was established as the criterion for consensus. At each round of consultation, non-consensual aspects were reformulated and new aspects suggested in the previous round were included. A measure of stability to conclude the consultation was determined when more than 70 % of experts sustained their opinion in successive rounds. RESULTS: Eight experts in orthopedics and six experts in imaging studies participated. After three rounds of consultations, consensus was reached in terms of 39 recommendations for follow-up, pre-surgical planning, and treatment. These were reorganized into 32 final recommendations. CONCLUSIONS: These are the first recommendations for the follow-up of children with leg length discrepancy agreed by expert consensus.

La asimetría de la longitud de los miembros inferiores es una afección en la cual la longitud de una pierna difiere de la contralateral, motivo de consulta frecuente en el consultorio del pediatra y del ortopedista infantil. El objetivo de nuestro trabajo fue desarrollar recomendaciones de seguimiento, planificación prequirúrgica y tratamiento de niños con asimetría de la longitud de los miembros inferiores mediante el consenso de expertos. Material y métodos. Se utilizó el método Delphi. Un grupo coordinador seleccionó el panel de expertos, diseñó y analizó cada una de las rondas de consulta. Los cuestionarios semiestructurados fueron enviados por correo electrónico en forma personalizada. Se estableció como criterio de consenso un acuerdo entre los expertos > 80 %. En cada una de las rondas, se reformularon los aspectos no consensuados y se agregaron nuevos sugeridos en la ronda anterior. Se consideró como medida de estabilidad para concluir la consulta cuando más del 70 % de los expertos no modificó su opinión en rondas sucesivas. Resultados. Participaron del consenso 8 expertos en ortopedia y 6 en diagnóstico por imágenes. Luego de 3 rondas de consulta, se logró el consenso en 39 recomendaciones referentes a seguimiento, planificación prequirúrgica y tratamiento. Fueron reagrupadas en 32 recomendaciones finales. Conclusiones. Estas son las primeras recomendaciones para el seguimiento de niños con asimetría de la longitud de los miembros inferiores mediante el consenso de expertos.

Van der Woude and Popliteal Pterygium Syndromes.

: Van der Woude syndrome is the most generic form of syndromic orofacial cleft, present in approximately 2% of all cleft patients. The lower lip pits with or without cleft lip and/or palate is typical of this syndrome. Popliteal pterygium syndrome (PPS), also known as popliteal web syndrome or fasciogenito-popliteal syndrome, was first described by Trelat in 1869, the incidence is approximately 1 in 300,000 live births. The term PPS was coined by Gorlin et al in 1968 based on the most unusual anomaly, the popliteal pterygium. Popliteal pterygium syndrome shares features with van der Woude syndrome but, in addition, is characterized by genital anomalies, syndactyly of fingers and toes, and toenail dysplasia. In some patients, oral or eyelid synechiae are present. Van der Woude syndrome and PPS are autosomal dominantly inherited disorders caused by heterozygous mutations in IRF6. OBJECTIVE:: To report the familial nature of the disease in the mother and son, and to summarize the clinical characteristics, treatment, and outcomes in both patients.

Treatment outcomes with hypofractionated high-dose radiation therapy for prostate cancer.

AIM: To report the treatment results of a retrospective cohort of prostate cancer patients treated with Hypo-RT with a high equivalent biological effective dose (BED). BACKGROUND: Hypofractionated radiotherapy (Hypo-RT) has gained popularity and interest in the treatment of prostate cancer. However, there are few experiences with adequate follow-up reporting treatment results using high equivalent dose with Hypo-RT. MATERIALS AND METHODS: We assigned 149 men with low-, intermediate- and high-risk prostate cancer to receive Hypo-RT with a total dose of 69 Gy/23 fractions. Late gastrointestinal (GI) and genitourinary (GU) toxicity were prospectively evaluated according to modified RTOG criteria. Biochemical no evidence of disease (bNED) was defined as the nadir prostate-specific antigen level plus 2 ng/mL. RESULTS: The median follow-up was 53 months. For the entire cohort, the 5-year bNED rate was 94.6%, and for low-, intermediate- and high-risk patients the 5-year bNED was 100%, 96.4%, and 86% (p = 0.007), respectively. The 5-year overall survival rate was 92%. Only 1 patient died from the disease at 48 months after treatment, giving a 5-year cancer-specific survival of 98%. The worst grade ≥2 rate GI and GU toxicity was 13.4% and 14%, respectively. No grade >3 toxicity was observed. The presence of grade ≥2 GI and GU toxicity at the last follow-up was only 1.3% and 3%, respectively. CONCLUSIONS: Hypo-RT (69 Gy/23 fractions) with a high equivalent BED produces excellent rates of biochemical control for low, intermediate and high-risk prostate cancer. The long term GU and GI toxicity rates were considered low and acceptable.

Intensity-modulated radiotherapy reduces toxicity with similar biochemical control compared with 3-dimensional conformal radiotherapy for prostate cancer: A randomized clinical trial.

BACKGROUND: The objective of this article was to report the results from a randomized clinical trial comparing intensity-modulated radiotherapy (IMRT) with 3-dimensonal conformal radiotherapy (3DCRT) for the treatment of prostate cancer on a hypofractionated schedule. METHODS: The authors randomly assigned 215 men who had localized prostate cancer to receive hypofractionated radiotherapy to a total dose of 70 grays (Gy) in 25 fractions (at 2.8 Gy per fraction) using either IMRT or 3DCRT. Acute and late gastrointestinal (GI) and genitourinary (GU) toxicity were prospectively evaluated according to modified Radiation Therapy Oncology Group criteria. Biochemical control was defined according to the Phoenix criteria (prostate-specific antigen nadir + 2 ng/mL). RESULTS: In total, 215 patients were enrolled in the IMRT group (n = 109) or the 3DCRT group (n = 106). The 3DCRT arm had a 27% rate of grade ≥ 2 acute GU toxicity compared with a 9% rate in the IMRT arm (P = .001) and a 24% rate of grade ≥ 2 acute GI toxicity compared with a 7% rate in the IMRT arm (P = .001). The maximal rate of grade ≥2 late GU toxicity during the entire period of follow-up was 3.7% in the IMRT group versus 12.3% in the 3DCRT group (P = .02). The maximal rate of grade ≥2 late GI toxicity during the entire follow-up was 6.4% in the IMRT group versus 21.7% in the 3DCRT group (P = .001). The 5-year rate of freedom from biochemical failure was 95.4% in the IMRT arm and 94.3% in the 3DCRT arm (P = .678). CONCLUSIONS: IMRT reduced the delivery of significant radiation doses to the bladder and rectum using a similar target volume. This dosimetric advantage resulted in a lower rate of acute/late grade ≥ 2 GI and GU toxicity for IMRT compared with 3DCRT. Cancer 2016;122:2004-11. © 2016 American Cancer Society.

Remodelación y deterioro en epifisiolisis de cadera después de la fijación in situ. Resultados preliminares / Slipped capital femoral epiphysis remodeling and deterioration after in situ fixation. Preliminary results

Introducción: Una vez detenida la progresion del deslizamiento, las caderas experimentan un fenomeno complejo de remodelacion. Mientras tanto, el choque femoro-acetabular provoca daño irreversible del cartilago articular. El proposito del trabajo es determinar si la remodelacion es suficiente para impedir el deterioro articular en el corto plazo. Materiales y Métodos: Se diseñó un estudio de cohorte retrospectivo de pacientes con deslizamientos moderados y graves, que recibieron como tratamiento la fijacion in situ. Se evaluó la capacidad de remodelación con el ángulo de Southwick y el ángulo alfa. El deterioro funcional se evaluó con el puntaje de Harris y el radiologico, con la escala de Tonnis. Seguimiento minimo: 4 años. Resultados: Diecisiete pacientes, mediana de seguimiento: 63 meses (Ri 55-81). El angulo de Southwick prequirurgico 57o (Ri 50-72) versus el posquirurgico 48o (Ri 45-74) disminuyó significativamente (p 0,023). lo mismo ocurrio con el angulo alfa complementario. El deterioro radiologico evaluado con la escala de Tonnis fue estadisticamente significativo (p 0,012). los resultados funcionales, cuantificados con el puntaje de Harris no mostraron diferencias estadisticamente significativas (p 0,49). Conclusiones: En esta serie, las epifisiolisis moderadas y graves fijadas in situ presentaron deterioro radiologico en 63 meses de seguimiento promedio. Sin embargo, la funcionalidad no se deterioro con la misma rapidez. Nivel de Evidencia: IV.

Background: After stopping the slip progression, hips undergo a remodeling complex phenomenon. Meanwhile femoro-acetabular shock causes irreversible joint cartilage damage. The purpose of the study is to determine if remodeling is sufficient to prevent joint deterioration in the short-term. Methods: a retrospective cohort study of patients with moderate and severe landslides, treated with in situ fixation was designed. Remodeling capacity was evaluated with Southwick angle and alpha angle. Functional and radiological impairment was evaluated with the Hip Harris Score and Tonnis scale, respectively. Minimum follow-up: 4 years. Results: Seventeen patients, median follow-up 63 months (iR 55-81). The pre-surgical Southwick angle 57o (iR 50-72) versus the postoperative one 48o (iR 45-74) significantly decreased (p 0.023). The same happened with the complementary angle alpha. The radiological deterioration was statistically significant (p 0.012). Functional results showed no statistically significant differences (p 0.49). Conclusions: in this series, moderate and severe slipped capital femoral epiphysis fixed in situ showed radiological deterioration during a 63-month follow-up. However, the functionality is not deteriorating as quickly. Level of Evidence: IV.

Deslizamientos epifisarios femorales proximales >30º. Procedimiento de Dunn modificado: evaluación anatómica y funcional en una cohorte retrospectiva / Sliped capital femoral epiphysis >30º. Modified Dunn procedure: anatomical and functional evaluation in a retrospective cohort

Introducción: La deformidad residual resultante de un deslizamiento epifisario femoral proximal moderado o grave conduce a osteoartritis prematura debida al choque femoroacetabular. Los objetivos del trabajo fueron evaluar la mejoría de la anatomía del fémur proximal y evaluar la función de la cadera en pacientes con deslizamiento epifisario femoral proximal >30 grados tratados con el procedimiento de Dunn modificado, a corto plazo. Materiales y Métodos: Cohorte retrospectiva de pacientes con deslizamiento epifisario femoral proximal >30 grados, tratados con luxación controlada de cadera y el procedimiento de Dunn modificado. Se evaluaron mediciones clínicas y radiológicas preoperatorias y posoperatorias, hallazgos intraoperatorios y funcionalidad con los puntajes de Harris y de D'Aubigne-Postel. Resultados: Trece casos, mediana de edad 12 años y mediana de seguimiento 14 meses. El ángulo de deslizamiento de Southwick preoperatorio (75 grados, RI 67-85) y posoperatorio (10 grados, RI 5-17) mostró una disminución estadísticamente significativa (p <0,001). El offset radio cabeza-cuello preoperatorio (-0,13) versus el posoperatorio (0,12) obtuvo una mejoría significativa (p 0,002). El 69,2 por ciento de los pacientes presentó daño de alguna estructura intraarticular. Los puntajes promedio de funcionalidad fueron 14,6 (muy buena mejoría) y 83,4 (bueno). Complicaciones: necrosis avascular 15,3 por ciento y condrólisis 15,3 por ciento. Conclusiones: Esta técnica restaura la anatomía del fémur proximal y la funcionalidad de la cadera a corto plazo. Aunque no disponemos de resultados a largo plazo, al menos en teoría, serían buenos. Sin embargo, la luxación controlada con Dunn modificado no está exenta de complicaciones y el riesgo de necrosis avascular y condrólisis persiste. Nivel de evidencia: Estudios terapéuticos - III.

Background: The residual deformity resulting from a moderate and/or severe proximal femoral epiphysis slipping (SCFE) leads to premature osteoarthritis due to impingement. The objectives were to assess improvement in the anatomy of the proximal femur and to evaluate hip function in patients with SCFE >30° treated with the modified Dunn procedure. Methods: A retrospective cohort of patients with SCFE >30° treated with hip dislocation control and modified Dunn procedure. Preoperative and postoperative clinical and radiographic measurements, intra-operative findings and functionality using Harris and D'Aubigne & Postel scores were evaluated. Results: Thirteen cases, median age 12 years, median follow-up 14 months. Southwick slip angle showed a statistically significant decrease (preoperative: 75, IR 67-85; postoperative: 10, IR 5-17) (p <0.001). The head-neck offset radius obtained a significant improvement (preoperative -0.13; postoperative: 0.12) (p 0.002). The 69.2% of patients presented intraarticular damage. The average scores for functionality were 14.6 (excellent improvement) and 83.4 (good). Complications: avascular necrosis 15.3% and chondrolysis 15.3%. Conclusions: This technique restores the anatomy of the proximal femur and hip functionality in the short term. Although we do not have long-term results, at least in theory they would be good. However, the dislocation controlled with modified Dunn procedure is not free of complications and the risk of avascular necrosis and chondrolysis persists. Level of evidence: Therapeutic studies - III.

Deslizamientos epifisarios femorales proximales >30º: Procedimiento de Dunn modificado Evaluación anatómica y funcional en una cohorte retrospectiva

Introducción: La deformidad residual resultante de un deslizamiento epifisario femoral proximal moderado o grave conduce a osteoartritis prematura debida al choque femoroacetabular. Los objetivos del trabajo fueron evaluar la mejoría de la anatomía del fémur proximal y evaluar la función de la cadera en pacientes con deslizamiento epifisario femoral proximal >30 grados tratados con el procedimiento de Dunn modificado, a corto plazo. Materiales y Métodos: Cohorte retrospectiva de pacientes con deslizamiento epifisario femoral proximal >30 grados, tratados con luxación controlada de cadera y el procedimiento de Dunn modificado. Se evaluaron mediciones clínicas y radiológicas preoperatorias y posoperatorias, hallazgos intraoperatorios y funcionalidad con los puntajes de Harris y de DAubigne-Postel. Resultados: Trece casos, mediana de edad 12 años y mediana de seguimiento 14 meses. El ángulo de deslizamiento de Southwick preoperatorio (75 grados, RI 67-85) y posoperatorio (10 grados, RI 5-17) mostró una disminución estadísticamente significativa (p <0,001). El offset radio cabeza-cuello preoperatorio (-0,13) versus el posoperatorio (0,12) obtuvo una mejoría significativa (p 0,002). El 69,2% de los pacientes presentó daño de alguna estructura intraarticular. Los puntajes promedio de funcionalidad fueron 14,6 (muy buena mejoría) y 83,4 (bueno). Complicaciones: necrosis avascular 15,3% y condrólisis 15,3%. Conclusiones: Esta técnica restaura la anatomía del fémur proximal y la funcionalidad de la cadera a corto plazo. Aunque no disponemos de resultados a largo plazo, al menos en teoría, serían buenos. Sin embargo, la luxación controlada con Dunn modificado no está exenta de complicaciones y el riesgo de necrosis avascular y condrólisis persiste.(AU)

Background: The residual deformity resulting from a moderate and/or severe proximal femoral epiphysis slipping (SCFE) leads to premature osteoarthritis due to impingement. The objectives were to assess improvement in the anatomy of the proximal femur and to evaluate hip function in patients with SCFE >30° treated with the modified Dunn procedure. Methods: A retrospective cohort of patients with SCFE >30° treated with hip dislocation control and modified Dunn procedure. Preoperative and postoperative clinical and radiographic measurements, intra-operative findings and functionality using Harris and DAubigne & Postel scores were evaluated. Results: Thirteen cases, median age 12 years, median follow-up 14 months. Southwick slip angle showed a statistically significant decrease (preoperative: 75, IR 67-85; postoperative: 10, IR 5-17) (p <0.001). The head-neck offset radius obtained a significant improvement (preoperative -0.13; postoperative: 0.12) (p 0.002). The 69.2% of patients presented intraarticular damage. The average scores for functionality were 14.6 (excellent improvement) and 83.4 (good). Complications: avascular necrosis 15.3% and chondrolysis 15.3%. Conclusions: This technique restores the anatomy of the proximal femur and hip functionality in the short term. Although we do not have long-term results, at least in theory they would be good. However, the dislocation controlled with modified Dunn procedure is not free of complications and the risk of avascular necrosis and chondrolysis persists.(AU)

Acute toxicity profile in prostate cancer with conventional and hypofractionated treatment.

PURPOSE: To compare the acute toxicities in radical treatment of prostate cancer between conventional schedule (C-ARM) with 78 Gy/39 fractions and hypofractionation conformal treatment (H-ARM) with 69 Gy/23 fractions. METHODS AND MATERIAL: This prospective double arm study consisted of 217 patients with prostate cancer, 112 in H-ARM and 105 in C-ARM arm. C-ARM received conventional six- field conformal radiotherapy with 78 Gy in 39 fractions while H-ARM received hypofractionation with 69 Gy in 23 fractions. Weekly assessment of acute reactions was done during treatment and with one, and 3 months using RTOG scale. Univariated analysis was performed to evaluate differences between the incidences of acute reaction in the treatment arms. Variables with p value less than 0.1 were included in the multivariated logistic regression. RESULTS: There was no difference between H-ARM versus C-ARM for severity and incidence in genitourinary (GU) and gastrointestinal (GI) acute toxicity. During the treatment comparing H-ARM with C-ARM no differences was observed for GI toxicity (grade 0-3; H-ARM=45.5%, 34%, 18.7% and 1.8% versus C-ARM=47.6%, 35.2%, 17.2% and 0). For acute GU toxicity no difference was detected between H-ARM (grade 0-3; 22.3%, 54.5%, 18.7% and 4.5%) and C-ARM (grade 0-3; 25.8%, 53.3%, 17.1% and 3.8%).At the 3- months follow-up, persistent Grade> =2 acute GU and GI toxicity were 2.5% and 1.8% in H-ARM versus 5.7% and 3% in C-ARM (p>0.05). In univariated and multivariated analyses, there was not any dosimetric predictor for GI and GU toxicity. CONCLUSIONS: Our data demonstrate that hypofractionated radiotherapy achieving high biological effective dose using conformal radiotherapy is feasible for prostate cancer, being well tolerated with minimal severe acute toxicity.

Deslizamientos epifisarios femorales proximales >30º. Procedimiento de Dunn modificado: evaluación anatómica y funcional en una cohorte retrospectiva / Sliped capital femoral epiphysis >30º. Modified Dunn procedure: anatomical and functional evaluation in a retrospective cohort

Introducción: La deformidad residual resultante de un deslizamiento epifisario femoral proximal moderado o grave conduce a osteoartritis prematura debida al choque femoroacetabular. Los objetivos del trabajo fueron evaluar la mejoría de la anatomía del fémur proximal y evaluar la función de la cadera en pacientes con deslizamiento epifisario femoral proximal >30 grados tratados con el procedimiento de Dunn modificado, a corto plazo. Materiales y Métodos: Cohorte retrospectiva de pacientes con deslizamiento epifisario femoral proximal >30 grados, tratados con luxación controlada de cadera y el procedimiento de Dunn modificado. Se evaluaron mediciones clínicas y radiológicas preoperatorias y posoperatorias, hallazgos intraoperatorios y funcionalidad con los puntajes de Harris y de DAubigne-Postel. Resultados: Trece casos, mediana de edad 12 años y mediana de seguimiento 14 meses. El ángulo de deslizamiento de Southwick preoperatorio (75 grados, RI 67-85) y posoperatorio (10 grados, RI 5-17) mostró una disminución estadísticamente significativa (p <0,001). El offset radio cabeza-cuello preoperatorio (-0,13) versus el posoperatorio (0,12) obtuvo una mejoría significativa (p 0,002). El 69,2 por ciento de los pacientes presentó daño de alguna estructura intraarticular. Los puntajes promedio de funcionalidad fueron 14,6 (muy buena mejoría) y 83,4 (bueno). Complicaciones: necrosis avascular 15,3 por ciento y condrólisis 15,3 por ciento. Conclusiones: Esta técnica restaura la anatomía del fémur proximal y la funcionalidad de la cadera a corto plazo. Aunque no disponemos de resultados a largo plazo, al menos en teoría, serían buenos. Sin embargo, la luxación controlada con Dunn modificado no está exenta de complicaciones y el riesgo de necrosis avascular y condrólisis persiste. Nivel de evidencia: Estudios terapéuticos - III.(AU)

Background: The residual deformity resulting from a moderate and/or severe proximal femoral epiphysis slipping (SCFE) leads to premature osteoarthritis due to impingement. The objectives were to assess improvement in the anatomy of the proximal femur and to evaluate hip function in patients with SCFE >30° treated with the modified Dunn procedure. Methods: A retrospective cohort of patients with SCFE >30° treated with hip dislocation control and modified Dunn procedure. Preoperative and postoperative clinical and radiographic measurements, intra-operative findings and functionality using Harris and DAubigne & Postel scores were evaluated. Results: Thirteen cases, median age 12 years, median follow-up 14 months. Southwick slip angle showed a statistically significant decrease (preoperative: 75, IR 67-85; postoperative: 10, IR 5-17) (p <0.001). The head-neck offset radius obtained a significant improvement (preoperative -0.13; postoperative: 0.12) (p 0.002). The 69.2% of patients presented intraarticular damage. The average scores for functionality were 14.6 (excellent improvement) and 83.4 (good). Complications: avascular necrosis 15.3% and chondrolysis 15.3%. Conclusions: This technique restores the anatomy of the proximal femur and hip functionality in the short term. Although we do not have long-term results, at least in theory they would be good. However, the dislocation controlled with modified Dunn procedure is not free of complications and the risk of avascular necrosis and chondrolysis persists. Level of evidence: Therapeutic studies - III.(AU)

Radiation therapy for Graves' ophthalmopathy: a systematic review and meta-analysis of randomized controlled trials / Radioterapia para oftalmopatia de Graves: uma revisão sistemática e meta-análise de ensaios clínicos randomizados e controlados

PURPOSE: To evaluate the efficacy of radiotherapy (RT) with total dose of 20 Gy (RT 20 Gy) in the treatment of Graves' ophthalmopathy. METHODS: A systematic review and meta-analysis of randomized controlled trials was performed comparing RT 20 Gy with or without glucocorticoid to clinical treatments for Graves' ophthalmopathy. The MEDLINE, EMBASE, Cochrane Library databases and recent relevant journals were searched. Relevant reports were reviewed by two reviewers. Response to radiotherapy was defined as clinical success according to each trial. We also evaluated the quality of life and whether RT to produce fewer side effects than other treatments. RESULTS: A total of 8 randomized controlled trials (439 patients) were identified. In the subgroup analysis, the overall response to treatment rates was better for: RT 20 Gy plus glucocorticoid vs glucocorticoids alone, OR=17.5 (CI95% 1.85-250, p=0.04), RT 20 Gy vs sham RT, OR= 3.15 (CI95%1.59-6.23, p=0.003) and RT 20Gy plus intravenous glucocorticoid vs RT 20Gy plus oral glucocorticoid, OR=4.15(CI95% 1.34-12.87, p=0.01). There were no differences between RT 20 Gy versus other fractionations and RT 20 Gy versus glucocorticoid alone. RT 20 Gy with or without glucocorticoids showed an improvement in diplopia grade, visual acuity, optic neuropathy, lid width, proptosis and ocular motility. No difference was seen for costs, intraocular pressure and quality of life. CONCLUSION: Our data have shown that RT 20 Gy should be offered as a valid therapeutic option to patients with moderate to severe ophthalmopathy. The effectiveness of orbital radiotherapy can be increased by the synergistic interaction with glucocorticoids. Moreover, RT 20 Gy is useful to improve a lot of ocular symptoms, excluding intraocular pressure, without any difference in quality of life and costs.

OBJETIVO: Avaliar a eficácia da radioterapia (RT) com dose total de 20 Gy (RT 20 Gy) no tratamento da oftalmopatia de Graves. MÉTODOS: Uma revisão sistemática e meta-análise de ensaios clínicos randomizados foram realizadas comparando RT 20 Gy, com ou sem glicocorticoides a tratamentos clinicos para a oftalmopatia de Graves. O MEDLINE, EMBASE, bases de dados da Biblioteca Cochrane e recentes de revistas relevantes foram pesquisados. Relatórios relevantes foram revisados por dois revisores. A resposta à radioterapia foi definida através do sucesso clinico de acordo a cada ensaio clínico. Nós também avaliamos a qualidade de vida e se a radioterapia produzia menos efeitos colaterais comparados a outras intervenções. RESULTADOS: Um total de 8 ensaios clínicos randomizados (439 pacientes) foram identificados. Na análise de subgrupo, a resposta global para as taxas de tratamento foi melhor para: RT 20 Gy além de glicocorticoides vs glicocorticoides sozinhos, OR=17,5 (IC95% 1,85-250, p=0,04), RT 20 Gy vs sham RT, OR=3,15 (IC95% 1,59-6,23, p=0,003) e RT 20 Gy além de glicocorticoides por via intravenosa RT 20 Gy além de glicocorticoides orais, OR=4,15 (IC95% 1,34-12,87, p=0,01). Não houve diferenças entre RT 20 Gy contra outros fracionamentos e 20 Gy RT contra glicocorticoides sozinhos. RT 20 Gy, com ou sem glicocorticoides mostraram uma melhoria no grau de diplopia, acuidade visual, neuropatia óptica, abertura palpebral, proptose e da motilidade ocular. Não foi observada diferença para os custos, a pressão intraocular e a qualidade de vida. CONCLUSÃO: Nossos dados mostraram que 20 Gy RT deve ser oferecida como uma opção terapêutica válida para pacientes com moderada a severa oftalmopatia de Graves. A eficácia da radioterapia orbital pode ser aumentada pela interação sinérgica com os glicocorticoides. Além disso, RT 20 Gy é útil para melhorar vários sintomas oculares, excluindo a pressão intraocular, sem qualquer diferença de qualidade de vida.

High-dose conformal radiotherapy reduces prostate cancer-specific mortality: results of a meta-analysis.

PURPOSE: To determine in a meta-analysis whether prostate cancer-specific mortality (PCSM), biochemical or clinical failure (BCF), and overall mortality (OM) in men with localized prostate cancer treated with conformal high-dose radiotherapy (HDRT) are better than those in men treated with conventional-dose radiotherapy (CDRT). METHODS AND MATERIALS: The MEDLINE, Embase, CANCERLIT, and Cochrane Library databases, as well as the proceedings of annual meetings, were systematically searched to identify randomized, controlled studies comparing conformal HDRT with CDRT for localized prostate cancer. RESULTS: Five randomized, controlled trials (2508 patients) that met the study criteria were identified. Pooled results from these randomized, controlled trials showed a significant reduction in the incidence of PCSM and BCF rates at 5 years in patients treated with HDRT (p = 0.04 and p < 0.0001, respectively), with an absolute risk reduction (ARR) of PCSM and BCF at 5 years of 1.7% and 12.6%, respectively. Two trials evaluated PCSM with 10 years of follow up. The pooled results from these trials showed a statistical benefit for HDRT in terms of PCSM (p = 0.03). In the subgroup analysis, trials that used androgen deprivation therapy (ADT) showed an ARR for BCF of 12.9% (number needed to treat = 7.7, p < 0.00001), whereas trials without ADT had an ARR of 13.6% (number needed to treat = 7, p < 0.00001). There was no difference in the OM rate at 5 and 10 years (p = 0.99 and p = 0.11, respectively) between the groups receiving HDRT and CDRT. CONCLUSIONS: This meta-analysis is the first study to show that HDRT is superior to CDRT in preventing disease progression and prostate cancer-specific death in trials that used conformational technique to increase the total dose. Despite the limitations of our study in evaluating the role of ADT and HDRT, our data show no benefit for HDRT arms in terms of BCF in trials with or without ADT.

Prevention of gynecomastia and breast pain caused by androgen deprivation therapy in prostate cancer: tamoxifen or radiotherapy?

PURPOSE: To determine, in a meta-analysis, whether gynecomastia and breast pain rates in men with prostate cancer treated with androgen deprivation therapy (ADT) are reduced if treated with prophylactic radiotherapy (RT) or tamoxifen (TMX). METHODS AND MATERIALS: The MEDLINE, EMBASE, CANCERLIT, and Cochrane Library databases, as well as proceedings of annual meetings, were systematically searched to identify randomized, controlled studies comparing RT or TMX with observation for men with prostate cancer using ADT. RESULTS: Six RCTs (three RT trials and three TMX trials, N = 777 patients total) were identified that met the study criteria. Pooled results from these RCTs comparing RT vs. observation showed a significant reduction in the incidence of gynecomastia and breast pain rates in patients treated with RT (odds ratio [OR] = 0.21, 95% confidence interval [CI] = 0.12-0.37, p < 0.0001, and OR = 0.34, 95% CI 0.20-0.57, p < 0.0001, respectively). Use of RT resulted in an absolute risk reduction (ARR) of 29.4% and 19.9%, with a number needed to treat (NNT) of 3.4 and 5 to avoid one case of gynecomastia and breast pain, respectively. Pooled results from trials comparing TMX vs. observation showed a statistical benefit for breast pain and gynecomastia in favor of TMX arms (OR = 0.04, 95% CI = 0.02-0.08, p < 0.0001 and OR = 0.07, 95% CI = 0.0-0.14, p < 0.00001). TMX resulted in an ARR = 64.1% and 47.6%, with an NNT of 1.56 and 2.1 to avoid one case of gynecomastia and breast pain, respectively. Considering adverse effects, TMX was 6 times more adverse effects than RT. CONCLUSIONS: Our data have shown that both TMX and RT prevented gynecomastia and breast pain in patients with prostate cancer receiving ADT for prostate cancer. Although TMX was two times more effective in preventing gynecomastia, RT should represent an effective and safe treatment option, to take into account mainly in patients with cardiovascular risk factors or thrombotic diathesis.

Prognostic indexes for brain metastases: which is the most powerful?

PURPOSE: The purpose of the present study was to compare the prognostic indexes (PIs) of patients with brain metastases (BMs) treated with whole brain radiotherapy (WBRT) using an artificial neural network. This analysis is important, because it evaluates the prognostic power of each PI to guide clinical decision-making and outcomes research. METHODS AND MATERIALS: A retrospective prognostic study was conducted of 412 patients with BMs who underwent WBRT between April 1998 and March 2010. The eligibility criteria for patients included having undergone WBRT or WBRT plus neurosurgery. The data were analyzed using the artificial neural network. The input neural data consisted of all prognostic factors included in the 5 PIs (recursive partitioning analysis, graded prognostic assessment [GPA], basic score for BMs, Rotterdam score, and Germany score). The data set was randomly divided into 300 training and 112 testing examples for survival prediction. All 5 PIs were compared using our database of 412 patients with BMs. The sensibility of the 5 indexes to predict survival according to their input variables was determined statistically using receiver operating characteristic curves. The importance of each variable from each PI was subsequently evaluated. RESULTS: The overall 1-, 2-, and 3-year survival rate was 22%, 10.2%, and 5.1%, respectively. All classes of PIs were significantly associated with survival (recursive partitioning analysis, P < .0001; GPA, P < .0001; basic score for BMs, P = .002; Rotterdam score, P = .001; and Germany score, P < .0001). Comparing the areas under the curves, the GPA was statistically most sensitive in predicting survival (GPA, 86%; recursive partitioning analysis, 81%; basic score for BMs, 79%; Rotterdam, 73%; and Germany score, 77%; P < .001). Among the variables included in each PI, the performance status and presence of extracranial metastases were the most important factors. CONCLUSION: A variety of prognostic models describe the survival of patients with BMs to a more or less satisfactory degree. Among the 5 PIs evaluated in the present study, GPA was the most powerful in predicting survival. Additional studies should include emerging biologic prognostic factors to improve the sensibility of these PIs.

Low or high fractionation dose ß-radiotherapy for pterygium? A randomized clinical trial.

PURPOSE: Postoperative adjuvant treatment using ß-radiotherapy (RT) is a proven technique for reducing the recurrence of pterygium. A randomized trial was conducted to determine whether a low fractionation dose of 2 Gy within 10 fractions would provide local control similar to that after a high fractionation dose of 5 Gy within 7 fractions for surgically resected pterygium. METHODS: A randomized trial was conducted in 200 patients (216 pterygia) between February 2006 and July 2007. Only patients with fresh pterygium resected using a bare sclera method and given RT within 3 days were included. Postoperative RT was delivered using a strontium-90 eye applicator. The pterygia were randomly treated using either 5 Gy within 7 fractions (Group 1) or 2 Gy within 10 fractions (Group 2). The local control rate was calculated from the date of surgery. RESULTS: Of the 216 pterygia included, 112 were allocated to Group 1 and 104 to Group 2. The 3-year local control rate for Groups 1 and 2 was 93.8% and 92.3%, respectively (p = .616). A statistically significant difference for cosmetic effect (p = .034), photophobia (p = .02), irritation (p = .001), and scleromalacia (p = .017) was noted in favor of Group 2. CONCLUSIONS: No better local control rate for postoperative pterygium was obtained using high-dose fractionation vs. low-dose fractionation. However, a low-dose fractionation schedule produced better cosmetic effects and resulted in fewer symptoms than high-dose fractionation. Moreover, pterygia can be safely treated in terms of local recurrence using RT schedules with a biologic effective dose of 24-52.5 Gy(10.).

Radiation therapy for Graves' ophthalmopathy: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: To evaluate the efficacy of radiotherapy (RT) with total dose of 20 Gy (RT 20 Gy) in the treatment of Graves' ophthalmopathy. METHODS: A systematic review and meta-analysis of randomized controlled trials was performed comparing RT 20 Gy with or without glucocorticoid to clinical treatments for Graves' ophthalmopathy. The MEDLINE, EMBASE, Cochrane Library databases and recent relevant journals were searched. Relevant reports were reviewed by two reviewers. Response to radiotherapy was defined as clinical success according to each trial. We also evaluated the quality of life and whether RT to produce fewer side effects than other treatments. RESULTS: A total of 8 randomized controlled trials (439 patients) were identified. In the subgroup analysis, the overall response to treatment rates was better for: RT 20 Gy plus glucocorticoid vs glucocorticoids alone, OR=17.5 (CI95% 1.85-250, p=0.04), RT 20 Gy vs sham RT, OR= 3.15 (CI95%1.59-6.23, p=0.003) and RT 20 Gy plus intravenous glucocorticoid vs RT 20Gy plus oral glucocorticoid, OR=4.15(CI95% 1.34-12.87, p=0.01). There were no differences between RT 20 Gy versus other fractionations and RT 20 Gy versus glucocorticoid alone. RT 20 Gy with or without glucocorticoids showed an improvement in diplopia grade, visual acuity, optic neuropathy, lid width, proptosis and ocular motility. No difference was seen for costs, intraocular pressure and quality of life. CONCLUSION: Our data have shown that RT 20 Gy should be offered as a valid therapeutic option to patients with moderate to severe ophthalmopathy. The effectiveness of orbital radiotherapy can be increased by the synergistic interaction with glucocorticoids. Moreover, RT 20 Gy is useful to improve a lot of ocular symptoms, excluding intraocular pressure, without any difference in quality of life and costs.

Surgical removal of metastases after successful treatment containing bevacizumab in metastatic colorectal cancer.

Metastatic colorectal cancer has a low cure rate. When resection of metastases is feasible, however, survival is increased. We present a case of a patient with metastases that responded well to bevacizumab-containing treatment. Consequently, surgical resection of metastases was possible resulting in increased survival.

Weekly gemcitabine and cisplatin in combination with radiotherapy in patients with locally advanced head-and-neck cancer: Phase I study.

PURPOSE: To define the maximum tolerated dose by describing the dose-limiting toxicity (DLT) of weekly gemcitabine and cisplatin in patients with locally advanced head-and-neck (LAHN) cancer concomitant to irradiation. METHODS AND MATERIALS: Patients with LAHN cancer were enrolled in a prospective, dose-escalation Phase I study. Toxicity was graded according to the Common Toxicity Criteria score. Maximum tolerated dose was defined when DLT developed in 2 of 6 patients. The starting dose of cisplatin was 20 mg/m(2) and that of gemcitabine was 10 mg/m(2) in 3 patients, with a subsequent dose escalation of 10 mg/m(2) of cisplatin only for 3 new patients. In the next levels, only a dose escalation of gemcitabine with 10 mg/m(2) for each new cohort was used (Level 1, 10 mg/m(2) of gemcitabine and 20 mg/m(2) of cisplatin; Level 2, 10 mg/m(2) of gemcitabine and 30 mg/m(2) of cisplatin; and Level 3, 20 mg/m(2) of gemcitabine and 30 mg/m(2) of cisplatin). Radiation therapy was administered by use of a conformal technique over a period of 6 to 7 weeks in 2.0-Gy daily fractions for 5 consecutive days per week to a total dose of 70 Gy. RESULTS: From 2008 to 2009, 12 patients completing 3 dose levels were included in the study. At Dose Level 3, 1 of 3 patients had DLT with Grade 3 mucositis. Of the next 3 required patients, 2 showed DLT with Grade 3 dermatitis. At a follow-up of 3 months, 10 of 12 evaluable patients (83.3%) obtained a complete response and 1 patient (8.3%) obtained a partial response. Among the complete responders, at a median follow-up of 10 months (range, 6-14 months), 9 patients are alive and disease free. CONCLUSION: Gemcitabine at low doses combined with cisplatin is a potent radiosensitizer effective in patients with LAHN cancer. The recommended Phase II dose is 10 mg/m(2) of gemcitabine and 30 mg/m(2) of cisplatin with an acceptable tolerability profile.

Evaluation of biologic effective dose and schedule of fractionation for preoperative radiotherapy for rectal cancer: meta-analyses and meta-regression.

PURPOSE: To evaluate whether the risk of local recurrence depends on the biologic effective dose (BED) or fractionation dose in patients with resectable rectal cancer undergoing preoperative radiotherapy (RT) compared with surgery alone. METHODS AND MATERIALS: A meta-analysis of randomized controlled trials (RCTs) was performed. The MEDLINE, Embase, CancerLit, and Cochrane Library databases were systematically searched for evidence. To evaluate the dose-response relationship, we conducted a meta-regression analysis. Four subgroups were created: Group 1, RCTs with a BED >30 Gy(10) and a short RT schedule; Group 2, RCTs with BED >30 Gy(10) and a long RT schedule; Group 3, RCTs with BED ≤ 30 Gy(10) and a short RT schedule; and Group 4, RCTs with BED ≤ 30 Gy(10) and a long RT schedule. RESULTS: Our review identified 21 RCTs, yielding 9,097 patients. The pooled results from these 21 randomized trials of preoperative RT showed a significant reduction in mortality for groups 1 (p = .004) and 2 (p = .03). For local recurrence, the results were also significant in groups 1 (p = .00001) and 2 (p = .00001).The only subgroup that showed a greater sphincter preservation (SP) rate than surgery was group 2 (p = .03). The dose-response curve was linear (p = .006), and RT decreased the risk of local recurrence by about 1.7% for each Gy(10) of BED. CONCLUSION: Our data have shown that RT with a BED of >30 Gy(10) is more efficient in reducing local recurrence and mortality rates than a BED of ≤ 30 Gy(10), independent of the schedule of fractionation used. A long RT schedule with a BED of >30 Gy(10) should be recommended for sphincter preservation.

Higher-than-conventional radiation doses in localized prostate cancer treatment: a meta-analysis of randomized, controlled trials.

PURPOSE: To determine in a meta-analysis whether the outcomes in men with localized prostate cancer treated with high-dose radiotherapy (HDRT) are better than those in men treated with conventional-dose radiotherapy (CDRT), by quantifying the effect of the total dose of radiotherapy on biochemical control (BC). METHODS AND MATERIALS: The MEDLINE, EMBASE, CANCERLIT, and Cochrane Library databases, as well as the proceedings of annual meetings, were systematically searched to identify randomized, controlled studies comparing HDRT with CDRT for localized prostate cancer. To evaluate the dose-response relationship, we conducted a meta-regression analysis of BC ratios by means of weighted linear regression. RESULTS: Seven RCTs with a total patient population of 2812 were identified that met the study criteria. Pooled results from these RCTs showed a significant reduction in the incidence of biochemical failure in those patients with prostate cancer treated with HDRT (p < 0.0001). However, there was no difference in the mortality rate (p = 0.38) and specific prostate cancer mortality rates (p = 0.45) between the groups receiving HDRT and CDRT. However, there were more cases of late Grade >2 gastrointestinal toxicity after HDRT than after CDRT. In the subgroup analysis, patients classified as being at low (p = 0.007), intermediate (p < 0.0001), and high risk (p < 0.0001) of biochemical failure all showed a benefit from HDRT. The meta-regression analysis also detected a linear correlation between the total dose of radiotherapy and biochemical failure (BC = -67.3 + [1.8 x radiotherapy total dose in Gy]; p = 0.04). CONCLUSIONS: Our meta-analysis showed that HDRT is superior to CDRT in preventing biochemical failure in low-, intermediate-, and high-risk prostate cancer patients, suggesting that this should be offered as a treatment for all patients, regardless of their risk status.