Prognosis Analysis of Early-stage Non-small Cell Lung Cancer Patients Treated with Stereotactic Body Radiotherapy / 中国肺癌杂志

BACKGROUND@#With the aging of the population and the increased importance of lung cancer screening, the number of early-stage lung cancer patients has been on the rise in recent years, which can be classified into operable early-stage lung cancer and inoperable early-stage lung cancer. The most common pathological type is non-small cell lung cancer (NSCLC). Stereotactic body radiation therapy (SBRT) is the optimal treatment for inoperable early-stage NSCLC. The aim of this study was to investigate the prognosis of early-stage NSCLC patients treated with SBRT and its influencing factors in order to reduce the side effects of radiotherapy and improve the survival and quality of life.@*METHODS@#Clinical data and follow-up outcomes of early-stage NSCLC patients treated with SBRT in our hospital from August 2010 to August 2020 were collected. Kaplan-Meier method was used to assess the prognosis, and the Cox proportional risk model was used for multivariate prognostic analysis.@*RESULTS@#A total of 165 patients were included with a median follow-up time of 43.2 (range: 4.8-132.1) mon. The local control (LC) rates at 1-yr, 2-yr and 5-yr were 98.1%, 94.8% and 86.5% respectively. Karnofsky performance status (KPS) score greater than 80 was an independent prognostic factor for LC (P=0.02). The overall survival (OS) rates at 1-yr, 2-yr and 5-yr were 97.6%, 93.0% and 68.9% respectively. A biological equivalent dose when α/β=10 (BED10) greater than 132 Gy was an independent prognostic factor for OS (P=0.04). Progression-free survival (PFS) rates at 1-yr, 2-yr and 5-yr were 93.3%, 79.5% and 55.3% respectively. The distance metastasis free survival (DMFS) rates at 1-yr, 2-yr and 5-yr were 94.5%, 83.2% and 58.4% respectively. BED10 greater than 150 Gy was an independent prognostic factor for DMFS (P=0.02). The regional control (RC) rates at 1-yr, 2-yr and 5-yr were 98.8%, 95.4% and 87.9% respectively.@*CONCLUSIONS@#SBRT is effective in treating early-stage NSCLC. KPS greater than 80 is an independent prognostic factor for LC; BED10 greater than 132 Gy is an independent prognostic factor for OS; BED10 greater than 150 Gy is an independent prognostic factor for DMFS.

Manejo multidisciplinario de las metástasis cerebrales: una revisión actualizada y un cambio de paradigma / Multidisciplinary management of brain metastases: An updated review and paradigm shift

Introducción: Las metástasis cerebrales (MC) representan una problemática importante de la salud pública, en promedio el 30% de los pacientes oncológicos desarrollarán MC siendo importante causa de morbilidad, ansiedad y mortalidad. El tratamiento con radioterapia, cirugía y sistémico son los pilares para el tratamiento y han tenido una evolución importante en la última década. Propósito de la revisión: Se proporciona información actualizada en relación a epidemiología, diagnóstico, pronóstico y tratamiento de metástasis cerebrales desde un enfoque multidisciplinariopara lograr individualizar su abordaje con el objetivo de proporcionar control oncológico y calidad de vida. También se discuten el acceso a nuevas terapias sistémicas, técnicas quirúrgicas y disponibilidad de tecnología para ofrecer técnicas avanzadas de radioterapia.Men saje principal: Conocer mutaciones específicas y receptores diana de los tumores permite elegir quimio-inmunoterapia o terapias dirigidas actuales que ofrecen mejor potencial de control tanto a nivel sistémico como intracraneal. La secuenciación de los tratamientos sistémicos y locales (cirugía, radio-cirugía, radioterapia holocraneal) deben ser discutidos desde un enfoque multidisciplinario Conclusión: Es importante poder estimar el pronóstico de los pacientes con MC, esto determinarla conducta terapéutica que puede variar desde cuidados sintomáticos hasta tratamientos más agresivos como resección neuroquirúrgica o radiocirugía.

In troduction:Brain metastases (BMs) represent a significant public health problem. An average of 30% of cancer patients develop BM, which is a significant cause of morbidity, anxiety, and mortality. Radio-therapy, surgery, and systemic treatment are the mainstays of treatment and have evolved significantly in the last decade.Pu rpose of the review: Updated information on the epidemiology, diagnosis, prognosis, and treatment of brain metastases from a multidisciplinary approach is provided to enable an individualized approach aimed at cancer control and quality of life. Access to new systemic therapies, surgical techniques, and availability of technology for advanced radiotherapy techniques are also discussed.Mai n message: Knowledge of specific mutations and targets of tumor receptors allows the selection of chemoimmunotherapy or current targeted therapies that offer better control potential at the systemic and intracranial levels. The sequence of systemic and local treatments (surgery, radiosurgery, whole brain radiation therapy) should be discussed as part of a multidisciplinary approach.C o nclusion: It is essential to estimate the prognosis of patients with BM, given that this will determine the therapeuticbehavior that can range from symptomatic care to more aggressive treatments such as neurosurgical resection or radiosurgery

Stereotactic body radiation therapy for patients with lung and liver oligometastases from colorectal cancer: a phase Ⅱ trial / 中华肿瘤杂志

Objective: To explore the safety and effectiveness of stereotactic body radiation therapy (SBRT) for oligometastases from colorectal cancer (CRC). Methods: This is a prospective, single-arm phase Ⅱ trial. Patients who had histologically proven CRC, 1 to 5 detectable liver or lung metastatic lesions with maximum diameter of any metastases ≤5 cm were eligible. SBRT was delivered to all lesions. The primary endpoint was 3-year local control (LC). The secondary endpoints were treatment-related acute toxicities of grade 3 and above, 1-year and 3-year overall survival (OS) and progression free survival (PFS). Survival analysis was performed using the Kaplan-Meier method and Log rank test. Results: Petients from 2016 to 2019 who were treated in Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. Forty-eight patients with 60 lesions were enrolled, including 37 liver lesions and 23 lung lesions. Forty-six patients had 1 or 2 lesions, with median diameter of 1.3 cm, the median biologically effective dose (BED(10)) was 100.0 Gy. The median follow-up was 19.5 months for all lesions. Twenty-five lesions developed local failure, the median local progression free survival was 15 months. The 1-year LC, OS and PFS was 70.2% (95% CI, 63.7%~76.7%), 89.0% (95% CI, 84.3%~93.7%) and 40.4% (95%CI, 33.0%~47.8%). The univariate analysis revealed that planning target volume (PTV) and total dose were independent prognostic factors of LC (P<0.05). For liver and lung lesions, the 1-year LC, OS and PFS was 58.7% and 89.4% (P=0.015), 89.3% and 86.5% (P=0.732), 30.5% and 65.6% (P=0.024), respectively. No patients developed acute toxicity of grade 3 and above. Conclusion: SBRT is safe and effective treatment method for oligometastases from CRC under precise respiratory motion management and robust quality assurance.

Dosimetric effect of patient arm position on Cyberknife radiosurgery for spinal tumors / 北京大学学报(医学版)

OBJECTIVE@#To assess the potential dosimetric effects of arms movement in patients with Cyberknife spine tumors.@*METHODS@#In the study, 12 patients with thoracic and lumbar tumors were retrospectively selected respectively. The contour of the patient's arms was sketched and the CT density was modified to be equivalent to air in order to simulate the extreme case when the arm was completely removed from the radiation fields. The dose of simulated plan was re-calculated with the original beam parameters and compared with the original plan. The changes of V100, D95, and D90, conformity index (CI) and heterogeneity index (HI) in planning target volume (PTV), as well as Dmax, D1cc and D2cc in the spinal cord, stomach, esophagus, and intestines were analyzed by comparing with the original plans.@*RESULTS@#Compared with the original treatment plan, V100, D95, D90 and CI of PTV for the simulated plan was increased by 0.86%, 2.02%, 1.97% and 0.80% respectively, the difference was statistically significant (P < 0.05). Dmax, D1cc and D2cc of spinal cord was increased by 2.35%, 0.59% and 1.49% on average, compared with the original plan, the difference was statistically significant (P < 0.05). The difference was statistically significant only in average D2cc of stomach, which was increased by 1.70%, compared with the original plan (P < 0.05). There was no significant difference in dose change of eso-phagus and intestine between the original and simulated plans.@*CONCLUSION@#This study analyzed the most extreme arm position in spinal tumor of radiation therapy based on Cyberknife. It was found that the change of arm position had little effect on dosimetry. In addition, with the change of arm position, the dose in PTV and organ at risk (OAR) increased, but the increase was relatively small. Therefore, in some special cases where the patient really can't keep the arm position consistent during treatment, reasonable adjustment can be accepted. However, in order to ensure accurate radiotherapy, patient position should be as stable and consistent as possible.

Comprehensive quality assurance for intracranial radiosurgery treatments using a postal system / Garantía de calidad para tratamientos de radiocirugía intracranial usando un sistema postal

Radiosurgery is a high-precision technique for delivering, in most cases, a single highly conformal dose to a stereotactically localized target. It can be indicated for small intracranial injury treatment, using either multiple sources of 60Co (γ rays) or high energy photon beams produced by linear accelerators. In order to minimize the impact of inaccurate localization of the target or dose delivery, a rigorous Quality Assurance (QA) program must be enforced, which should include an independent auditing system. This work proposes a simple and reliable postal QA phantom to be used as an independent evaluation. In it two important parameters were verified such as, the dosimetric precision of the planning system, by comparing the absorbed doses measured in the target volume using different dosimeters (ionization chamber, films, thermoluminescent dosimeters and L-alanine dosimeters) all calibrated against a small volume ion chamber. The exact positioning of the target volume was localized using air spaces and small steel spheres to find the appropriate target coordinates. The head phantom and the instruction sheets were extensively tested and sent by mail to selected institutions. The overall results were very encouraging and suggest that the proposed phantom may be used as a postal system as part of an independent QA tool in radiosurgery.

La radiocirugía es una técnica de alta precisión para administrar, en la mayoría de los casos, una sola dosis altamente conformada en un objetivo localizado estereotípicamente. Puede estar indicado para el tratamiento de pequeñas lesiones intracraneales, utilizando múltiples fuentes de 60Co (rayos γ) o haces de fotones de alta energía producidos por aceleradores lineales. Con el fin de minimizar el impacto de la ubicación inexacta de la administración de la meta o de la dosis, se debe aplicar un riguroso programa de control de calidad (QA), que debe incluir un sistema de auditoría independiente. Este documento propone un fantoma postal de control de calidad simple y fiable que se utilizará como evaluación independiente. Se verificó dos parámetros importantes, como la precisión dosimétrica del sistema de planificación, comparando las dosis absorbidas medidas en el volumen objetivo mediante diferentes dosis (cámara de ionización, películas, dosímetros Termoluminiscentes y dosímetros de L-alanina) todos calibrados con una pequeña cámara de iones de volumen. El posicionamiento exacto del volumen objetivo se localizó utilizando espacios aéreos y pequeñas esferas de acero para encontrar las coordenadas de destino adecuadas. El fantoma principal y las hojas de instrucciones fueron ampliamente probados y enviados por correo a instituciones seleccionadas. Los resultados generales fueron muy alentadores y sugieren que el fantoma propuesto puede utilizarse como sistema postal como parte de una herramienta independiente de control de calidad en radiocirugía.

Multiple cerebral aneurysms originating from previously resected cardiac myxoma

Primary cardiac tumors are very rare, accounting for 0,001 ­0,03% in autopsy series, cardiac myxoma (CM) account for approximately 50% of them. Association between CM and cerebral aneurysm is well documented in this condition but the occurrence of cerebral aneurysm after resection of CM is very rare, with only 40 reports in medical literature. We present a case of a 45 years old female patient with multiple cerebral aneurysms 2 years after a successful resection of cardiac myxoma, submitted to radiosurgery for 2 bigger aneurysms with good results. This report ads to literature new clinical findings and a hypothesis of radiosurgery as an effective option of treatment for cerebral aneurysms with origin in CM. Keywords: Cardiac Myxoma; Cerebral aneurysm; Radiosurgery; Neurosurgery.

Dosimetric verification of stereotactic body radiotherapy treatment plan via ArcCHECK-3DVH system / 中南大学学报(医学版)

OBJECTIVES@#To study the feasibility of ArcCHECK-3DVH system in dosimetric verification for stereotactic body radiaotherapy (SBRT) with flattening filter free (FFF) model.@*METHODS@#SBRT treatment plans for 57 patients were introduced into ArcCHECK phantom and recalculated. The calculated dose distribution of treatment planning system and the measured dose distribution of ArcCHECK phantom were compared by γ analysis. Then the 3 dimensional dose distribution of target and organs at risk was reconstructed by 3DVH software. The reconstructed dose and calculated dose with treatment planning system (TPS) were compared, and the dose volume γ pass rate and deviation of dose volume parameters to the target and organs at risk were quantitatively valuated.@*RESULTS@#Based on the threshold criteria (3%, 3 mm, 10%), namely the deviation of measuring points between the planned value and the measured value was less than 3%, and the proportion of points with similar values in the plane or sphere with the center of the point and the radius of 3 mm was 10%, the relative and absolute dose pass rates of SBRT treatment plans in ArcCHECK system via γ analysis were greater than 95%. Based on the stricter threshold criteria (2%, 2 mm, 10%), the relative and absolute dose pass rates of SBRT treatment plan in ArcCHECK system via γ analysis were about 93%. In 3DVH dose verification, the γ pass rate of target and organs at risk was exceed 97%, and the deviations in 3DVH of the target and organs at risk were less than ±5%.@*CONCLUSIONS@#The ArcCHECK-3DVH system in dose verification can provide more comprehensive dose distribution information to reasonably evaluate the SBRT plan, with more significance for guiding clinical treatment.

Tratamiento con CyberKnife®: descripción de la respuesta y los efectos adversos en las metástasis cerebrales / Description of brain metastasis response and adverse effects to CyberKnife® treatment

RESUMEN Introducción: la primera causa de muerte por cáncer son las metástasis. La supervivencia media, para pacientes no tratados, es máximo de tres meses, que pueden extenderse de seis a doce con radioterapia y quimioterapia, dependiendo del tumor. La radiocirugía estereotáctica dirige la radiación ionizante a una metástasis guiada por tomografía computarizada o resonancia magnética, reduciendo así la radiación en el tejido normal y los efectos adversos. Su principal objetivo es lograr el control tumoral en los pacientes con oligometástasis. Métodos: estudio observacional, retrospectivo, con fuente mixta; se describen los resultados del tratamiento con CyberKnife® en metástasis cerebrales. Resultados: se evaluaron 31 pacientes con 62 metástasis, la edad media fue de 54 años y 74,2 % fueron mujeres. El cáncer de pulmón fue el origen más frecuente (54,8 %), La mitad de los casos tenía más de dos metástasis. La ubicación más común fue en los lóbulos frontales (33,9 %), siendo necróticas el 48,4 % de las lesiones. Hubo tratamiento previo en el 69,4 % de los tumores. Hubo radionecrosis en el 19,4 % de las lesiones, edema vasogénico en 77,4 % de ellas y recaída en 59,7 %. Se redujo el tamaño del tumor en el 80,7 % de las lesiones y se alcanzó el control tumoral en el 83,9 % de estas. Conclusión: el tratamiento con CyberKnife® logró el control en, por lo menos, cuatro quintas partes de las lesiones, con influencia de la ubicación de las metástasis en el sistema nervioso central y una aceptable prevalencia de la radionecrosis como complicación.

SUMMARY Background: Cancer ́s first cause of death are metastases. Mean survival for untreated patients is 3 months, which can extend to six or twelve months with conventional radiotherapy or chemotherapy, depending on the tumor. Stereotactic radiosurgery is a method which aims an ionizing radiation dose towards an intracranial target, guided by computarized tomography or magnetic resonance, reducing radiation on healthy brain tissue, as well as adverse effects. Its main indication is to achieve tumor control in patients with oligometastases. Methods: Retrospective, observational study, with primary and secondary sources for data, for describing results of CyberKnife® treatment. Results: Data were available for 31 patients and 62 metastases. Mean age was 54 years, 74,19% were women. Lung cancer was the most frequent primary tumor (54,8%); half of the cases had more than two metastases; most common location was frontal lobes (33,9%), being 48,4% of the tumors morphologically necrotic. There was a previous treatment in 69,4% of the tumors. There was radionecrosis in 19,4% of the metastases, vasogenic edema in 77,4% of them and relapses in 59,7% of the tumors. Tumor size was reduced in 80,7% of the metastases and tumor control was achieved in 83,9% of them. Conclusions: CyberKnife® was able to achieve control in at least four fifths of the treated metastases, with a relevant influence of metastases ́ location in central nervous and an acceptable prevalence of radionecrosis as a complication.

Comparación dosimétrica en radiocirugía intracraneal entre Cyberknife y un bisturí de rayos gamma y su puesta en marcha Centroamérica / Dosimetric comparison in intracranial radiosurgery between Cyberknife and a gamma knife and its implementation Central America

Introducción: La dupla Cyberknife y bisturí de rayos gamma (Infini) que se describe es la primera en Latinoamérica. Ambas máquinas han mostrado ser los mejores equipos para radiocirugía intracraneal. Se describe la experiencia inicial de Cyberknife en Centroamérica y su incorporación a un programa existente de bisturí de rayos gamma por vía de análisis comparativos dosimétricos. Material y método: En el año 2019 se realizaron planes comparativos y se trataron 180 pacientes con radiocirugía intracraneal con ambos sistemas tanto en patología tumoral, como vascular y funcional. Resultados: En el análisis dosimétrico comparativo en el gradiente de dosis de Infini mostró ser superior a Cyberknife en todos los casos. Para una esfera utilizando el colimador de 4 mm en Infini y de 5 mm en Cyberknife utilizando un plan isocéntrico con el -Trigeminal Path- el gradiente de dosis para Infini fue de 1.5 y para Cyberknife de 1.66. Para los casos de patología el gradiente de dosis media para Infini fue de 3 mm y para Cyberknife de 3.8 mm. Dando un puntaje de gradiente de dosis (Gradient Score Index) si Infini fuese de 100, Cyberknife obtuvo 87.3. Cyberknife mostró mejor conformalidad y cobertura (97% versus 96%) para todos los targets. Entre enero 2019 y enero 2020 se realizaron 180 radiocirugías, 60 con Cyberknife y 120 con Infini, 60 pacientes recibieron 146 sesiones con Cyberknife, radiocirugía fraccionada 39 (65%) y 21 (35%) en sesión única. Las dosis medias en tumores en dosis única fue 15 Gy (12.5 a 25 Gy) y en radiocirugía fraccionada 21 Gy (18 y 35). Ningún paciente ha experimentado toxicidad mayor a grado dos. Conclusiones: El bisturí de rayos gamma rotatorio reveló superioridad en gradiente de dosis con relación al Cyberknife. En su primer año Cyberknife ha mostrado ser una herramienta segura en el tratamiento de patología intracraneal. Más seguimiento clínico y radiológico es necesario para verificar su efectividad comparativa

Introduction: The match between Cyberknife and Infini here described in this article is the first in Latinamerica. Both machines have proven to be the best for intracranial radiosurgery, we describe our initial experience with Cyberknife in Central America and how it was incorporated in an existing gamma ray program by ways of dosimetry comparisons. Methods: During 2019 comparative plans were made and a total of 180 patients received intracranial radiosurgery with both technologies, patients were treated for tumors, vascular anomalies, and functional pathology. Results: Basic dosimetry analysis regarding dose gradient the Infini proved superior to Cyberknife in all plans. For a sphere using the 4 mm collimator in Infini and the 5 mm in Cyberknife along with an isocentric plan using the -Trigeminal Path- dose gradient was 1.5 for Infini and 1.66 for Cyberknife. For the pathology cases Infini was 3 mm and for Cyberknife 3.8 mm on mean. Giving a Gradient Score Index (GSI) if Infini would be 100, Cyberknife would be 87.3. Cyberknife showed better conformality and coverage for all pathology targets (97% versus 96%). From January 2019 to January 2020, 180 intracranial radiosurgeries were done, 60 with Cyberknife and 120 with Infini, 60 patients received 146 sessions with Cyberknife, fractionated scheme 39 (65%) and 21 (35%) single dose. The median dose for tumors was 15 Gy (12.5 a 25 Gy) for single session and 21 Gy (18 y 35) for fractionated scheme. No patient experienced a higher toxicity tan grade two. Conclusions: In its first year Cyberknife has shown to be safe in treating intracranial pathology. Infini had a better dose gradient than Cyberknife. Longer clinical and radiological follow-up is needed to verify its comparative effectiveness.

Metástasis sintomáticas en cerebro superiores a 8. 5 cm3 manejados con radiocirugía / Symptomatic brain metastases greater than 8.5 cm3 managed with radiosurgery

Introducción: Las recomendaciones en el manejo de metástasis superiores a 2 cm especialmente las sintomáticas sugieren cirugía como primera opción. En el presente artículo se discute el papel de radiocirugía como primer manejo de estos pacientes. Material y método: Se evaluaron 37 pacientes sintomáticos con lesiones metastásicas superiores a 8.5 cc tratados con radiocirugía entre el 2011 y el 2018. Resultados: La media de volumen fue de 12.5 cc (8.5-78.4), 9 (24%) pacientes fueron tratados utilizando LINAC, el volumen medio fue de 20 cc (9.2-70 cc). Los tratamientos con Gamma-Ray fueron administrados a 28 (76%) pacientes, 9 (32%) de ellos en protocolo de radiocirugía adaptativa, la dosis para todo el grupo fue de 13.8 Gy (7.5-18 Gy), con dosis media de 17.9 Gy, el volumen medio fue de 16.3 cc (8.5-78.4 cc) para gamma. El Karnofsky al inicio era de 60 (50-70) y de 80 (60-100) a los 30 días (P=0.0001). A los 30 días, 95% de las lesiones habían reducido su tamaño en un 74% (11-95%). La sobrevida media de la serie fue de 19 meses (4-34), el riesgo acumulado de muerte del SNC fue de 5.4%. Conclusiones: Radiocirugía en nuestra experiencia ha mostrado ser eficaz en el control de metástasis a cerebro de gran tamaño, reduciendo la necesidad de cirugí

Introduction: Current recommendations with regards to metastases larger than 2 cm specially in symptomatic patients suggest surgery as a first choice. We analyze the role of upfront radiosurgery as first line of treatment in such patients. Methods: 37 symptomatic patients that harbored tumors greater than 8.5 cc in volume were treated from 2011 to January 2018. Results: The median tumor volume was 12.5 cc (8.5-78.4), 9 (24%) patients were treated with LINAC with a volume of 20 cc (9.2-70 cc). The treatments with GammaRay were administrated to 28 (76%) patients, 9 (32%) of them with adaptive radiosurgery protocol, the prescription dose for the gamma group was 13.8 Gy (7.5-18Gy) mean dose of 17.9 Gy (13.2-23.3 Gy) with a mean volume of 16.3 cc (8.5-78.4 cc). Karnofsky score was 60 (50-70) the day of treatment and 80 (60-100) at 30 days (P=0.0001). At 30 days, 95% of the tumors had reduced in size in a 74% (11-95%) for those evaluated. Median survival was 19 months (4-34), with an accumulative risk of death from central nervous progression of 5.4%. Conclusions: Radiosurgery in our experience has shown to be effective in controlling large metastases, reducing the need for open surgery.

Avaliação prospectiva da correlação entre células tumorais circulantes e controle da doença encefálica após radioterapia focal de metástases encefálicas de câncer da mama / Prospective assessment of the correlation between circulating tumor cells and control of brain disease after focal radiotherapy of breast cancer brain metastases

Introdução: Predizer o risco de progressão encefálica distante (PED) precoce é um recurso útil e premente para a decisão terapêutica em pacientes candidatas ao tratamento local de metástases encefálicas. Este estudo tem como objetivo analisar a correlação entre células tumorais circulantes (CTCs) e controle da doença encefálica após radioterapia estereotática/radiocirurgia (RTE) de metástases encefálicas de câncer da mama (ME). Métodos: Avaliação prospectiva de CTC antes (CTC1) e 4­5 semanas após (CTC2) a RTE de ME e suas relações com o número de lesões sugestivas de ME (NL). As CTCs foram isoladas e quantificadas pelo método ISET (Rarecells, França) e analisadas por imunocitoquímica para avaliar a expressão das proteínas COX2, EGFR, ST6GALNAC5, NOTCH1 e HER2. Sobrevida livre de progressão encefálica distante (SLPED), o objetivo primário, sobrevida livre de progressão encefálica com envolvimento difuso (SLPED-ED), definida como progressão com mais de 4 novas ME ou carcinomatose meníngea, e sobrevida global (SG) foram estimadas pelo estimador de Kaplan-Meier. Testes de log-rank foram aplicados a fim de comparar as curvas de sobrevida. Para análise multivariada dos fatores prognósticos que afetaram a SPED e SG, foi ajustado o modelo proporcional de Cox. Análise de risco competitivo para SLPED na presença do óbito foi realizada. Resultados: Foram incluídas 39 pacientes entre novembro de 2016 e fevereiro de 2018. A idade mediana no momento da RTE foi 54 (34-70) anos e a avaliação prognóstica graduada doença-específica (DS-GPA) foi 1,5­2 em 17,5% e 2,5­4 em 82,5% das pacientes. CTCs foram detectadas em todas as 39 pacientes antes da RTE e a CTC1 mediana foi 2 CTC/mL. Após a RTE, CTCs foram detectadas em 34 das 35 pacientes (4 mortes entre CTC1 e CTC2) e a CTC2 mediana foi 2,33 CTC/mL. Após seguimento mediano de 16,6 (IC95%: 14,8­18,4) meses, 15 pacientes evoluíram com PED, sendo 6 com progressão encefálica distante com envolvimento difuso (PED-ED), e 16 pacientes faleceram. A SLPED, SLPED-ED e SG mediana foram 15,3, 14,1 e 19,5 meses, respectivamente. A incidência cumulativa, com a morte como risco competitivo, de PED em 6 meses foi 40% nas pacientes com CTC1 ≤ 0,5 e 8,82% nas pacientes com CTC1 > 0,5 CTC/mL (p = 0,007) e a de PED-ED em 6 meses foi 40% nas pacientes com CTC1 ≤ 0.5 e 0 nas pacientes com CTC1 > 0,5 CTC/mL (p = 0,005) e 25% nas pacientes com NL/CTC1 > 6,8 e 2,65% com NL/CTC1 ≤ 6,8 (p = 0,063). Na análise mutivariada, a SLPED foi inferior nas pacientes com CTC1 ≤ 0,5 CTC/mL (HR 8,27, IC95%:2,12­32,3; p = 0,002) e superior nas pacientes com imunofenótipo HER2-positivo (HR 0,128, IC95%:0,025­0,534; p = 0,013), a SLPED-ED foi inferior nas pacientes com CTC1 ≤ 0,5 CTC/mL (HR 10,22, IC95%:1,99­52,41; p = 0,005) e a SG foi superior nas pacientes com imunofenótipo HER2-positivo (HR 0,073, IC95%:0,018-0,288; p < 0,0001) e luminal B (HR 0,224, IC95%:0,062­0,816; p = 0,023) e nas pacientes com NL/CTC1 ≤ 2,2 (HR 0,159, 95% CI 0,05­0,505; p = 0,002). Não houve associação entre a expressão das proteínas nas CTCs e PED e SG. Conclusões: CTC1 foi um fator prognóstico independente de SLPED e SLPED-ED e NL/CTC1 foi um fator prognóstico independente de SG e um potencial fator prognóstico de PED-ED em 6 meses. Estes dados sugerem que CTC1 e NL/CTC1 podem ter um papel como biomarcador da PED-ED precoce, auxiliando a definir o momento e o tipo da radioterapia de resgate a fim de otimizar o controle das ME

Introduction: Predicting the risk of early distant brain failure (DBF) is a useful and demanding resource for management decisions in patients who are candidates to local treatment of brain metastasis. This study aims to analyze the correlation between circulating tumor cells (CTCs) and brain disease control after stereotactic radiotherapy/radiosurgery (SRT) for breast cancer brain metastasis (BM). Methods: Prospective assessment of CTCs before (CTC1) and 4­5 weeks after (CTC2) SRT for BM and its relations with the number of suggestive lesions of BM (NL). CTCs were isolated and quantified by the ISET method (Rarecells, France) and analyzed by immunocytochemistry to evaluate the expression of the proteins COX2, EGFR, ST6GALNAC5, NOTCH1 e HER2. Distant brain failure-free survival (DBFFS), the primary endpoint, diffuse distant brain failure-free survival (D-DBFFS), defined as progression with more than 4 new BM or meningeal carcinomatosis, and overall survival (OS) were estimated by Kaplan-Meier estimator. Log-rank tests were applied in order to compare the survival curves. For multivariate analysis of prognostic factors that affected DBFFS and OS, the Cox proportional model was adjusted. Competing risk analysis for DBFFS in the presence of death was performed. Results: 39 patients were included between November 2016 and February 2018. The median age at SRT was 54 (34-70) years and the diagnosis-specific graded prognostic assessment (DS-GPA) was 1.5­2 in 17.5% and 2.5­4 in 82.5% of them. CTCs were detected in all 39 patients before SRT and the median CTC1 was 2 CTC/mL. After SRT, CTCs were detected in 34 of 35 patients (4 deaths between CTC1 and CTC2) and the median CTC2 was 2.33 CTC/mL. After a median follow-up of 16.6 (95% CI: 14.8­18.4) months, there were 15 patients with DBF, being 6 with diffuse distant brain failure (D-DBF), and 16 deaths. The median DBFFS, D-DBFFS and OS were 15.3, 14.1 and 19.5 months, respectively. The cumulative incidence, with death as competing risk factor, of DBF at 6 months was 40% in patients with CTC1 ≤ 0.5 and 8.82% in patients with CTC1 > 0.5 CTC/mL (p = 0.007) and of D-DBF at 6 months was 40% in patients with CTC1 ≤ 0.5 and 0 in patients with CTC1 > 0.5 CTC/mL (p = 0.005) and 25% in patients with NL/CTC1 > 6.8 and 2.65% with NL/CTC1 ≤ 6.8 (p = 0.063). On multivariate analysis, DBFFS was inferior in patients with CTC1 ≤ 0.5 CTC/mL (HR 8.27, 95% CI 2.12­32.3; p = 0.002) and superior in patients with immunophenotype HER2-positive (HR 0.128, 95% CI 0.025­0.534; p = 0.013), D-DBFFS was inferior in patients with CTC1 ≤ 0.5 CTC/mL (HR 10.22, 95% CI 1.99­52.41; p = 0.005) and OS was superior in patients with immunophenotype HER2-positive (HR 0.073, 95% CI 0.018-0.288; p < 0.0001) and luminal B (HR 0.224, 95% CI 0.062­0.816; p = 0.023) and in patients with NL/CTC1 ≤ 2.2 (HR 0.159, 95% CI 0.05­0.505; p = 0.002). There was no association between protein expression in CTCs and DBF and OS. Conclusions: CTC1 was an independent prognostic factor of DBFFS and D-DBFFS and NL/CTC1 was an independent prognostic factor of OS and a potential prognostic factor of D-DBF at 6 months. These data suggest that CTC1 and NL/CTC1 may have a role as a biomarker of early D-DBF, helping define the timing and type of salvage radiotherapy in order to optimize the control of BM

Gamma Knife Radiosurgery on the Trigeminal Root Entry Zone for Idiopathic Trigeminal Neuralgia: Results and a Review of the Literature

Radiocirugía cerebral estereotáctica en el tratamiento de tumores de base de cráneo / Stereotactic brain radiosurgery in the treatment of skull base tumors

La radiocirugía estereotáctica ha demostrado efectividad en el tratamiento multimodal de los tumores de base de cráneo, de todas maneras se sugiere que en áreas radiobioló;gicamente sensibles (ej. nervios ó;pticos y tronco cerebral) la dosis radiante debería reducirse por los efectos radiotó;xicos. Para evitar la ineficacia terapó;©utica, una alternativa recientemente implementada es la radiocirugía multisesió;n (RCH). Se analizó; en forma retrospectiva una serie de tumores de base de cráneo, con el fin de evaluar el tratamiento con RCH a travó;©s del control tumoral en las imágenes post-tratamiento. Se evaluó; tambín edad, sexo, histología tumoral, volumen tumoral, protocolo radiante, Karnofsky performance status (KPS) pre-tratamiento y neurocirugía y tratamiento radiante previos. Fueron tratados 84 pacientes entre enero 2009 y enero 2017. La mediana de edad fue 51.5 aó;±os; sexo femenino: 53.6%. Hubo un 92.7% de no-progresió;n luego del tratamiento, con una mediana de tiempo de seguimiento de 36 meses. Los tumores tratados fueron principalmente adenomas hipofisarios, neurinomas del acó;ºstico, y meningiomas de base de cráneo. La mayoría de los pacientes recibió; un esquema de tratamiento fraccionado de 5 días, con una dosis total de 25 Gy. No se observó; radiotoxicidad tardía clínicamente manifiesta. En el análisis multivariado, un KPS alto pre-tratamiento fue significativamente asociado a la no-progresió;n tumoral. En esta serie, la alta incidencia de no-progresió;n tumoral indicaría que el tratamiento con RCH podría ser una opció;n terapó;©utica en algunos casos de tumores de base de cráneo, principalmente recurrencias o remanencias tumorales de adenomas hipofisarios, neurinomas y meningiomas.

Stereotactic radiosurgery has shown effectiveness in the multimodal treatment of skull base tumors, however it is suggested that in radiobiologically sensitive areas (eg. optic nerves and brainstem) the radiation dose should be reduced due to radiotoxic effects. To avoid the consequent therapeutic ineffectiveness, a recently implemented alternative is multisession radiosurgery (RCH). We retrospectively analyzed a series of patients with skull base tumors, in order to evaluate the treatment with RCH through tumor control in the post-treatment images. Age, sex, tumor histology, tumor volume, radiation protocol, pre-treatment Karnofsky performance status (KPS) previous neurosurgery and radiant treatment were also evaluated. Eighty-four patients were treated between January 2009 and January 2017. The median age was 51.5 years; females: 53.6%. There was a 92.7% non-progression after treatment, with a median follow-up time of 36 months. Treated tumors were mainly pituitary adenomas, acoustic schwannomas, and skull base meningiomas. Most of the patients received a 5-day fractionated treatment scheme, with a total dose of 25 Gy. No clinically manifest late radiotoxicity was observed. In the multivariate analysis, a high pre-treatment KPS was significantly associated with tumor non-progression. In our series, the high incidence of tumor non-progression would indicate that treatment with RCH could be a therapeutic option in some cases of skull-base tumors, mainly recurrences or tumor residuals of pituitary adenomas, neurinomas and meningiomas.

Resultados de la conización por radiocirugía en pacientesatendidas en consulta de patología de cuello uterino / Results of Conization by Radiosurgery in patients treated in a Cervical Pathology Clinic

Introducción: La radiocirugía tiene como objetivo proporcionar una herramienta de diagnóstico y tratamiento. Objetivos: Describir los resultados de la conización por radiocirugía en pacientes atendidas en la consulta de patología de cuello uterino de la institución. Métodos: Se realizó una investigación descriptiva de corte transversal en el Hospital General Docente Mártires del 9 de Abril de Sagua la Grande, Villa Clara, Cuba. La población de estudio estuvo conformada por la totalidad de 256 pacientes atendidas en la consulta de patología de cuello uterino que fueron sometidas a conización por radiocirugía, entre enero 2013 y diciembre 2015. Para la recogida de la información se empleó la revisión de documentos y se confeccionó un modelo de recogida de datos. Resultados: El diagnóstico preoperatorio que aportó mayor cantidad de casos fue el NIC III (displasia severa) (78 casos; 30,5 por ciento). Conclusiones: Las lesiones premalignas en el presente estudio comenzaron a aparecer con marcada incidencia a partir de los 20 años y hasta los 49, sobresaliendo el grupo de 30 - 39 años. El aumento en el número de parejas sexuales, así como el comienzo temprano de las relaciones sexuales incrementan el riesgo de padecer lesiones intraepiteliales en el cuello del útero. A partir de los cinco años de iniciada las relaciones sexuales comienzan a aparecer las lesiones intraepiteliales cervicales, el diagnóstico preoperatorio que aportó mayor cantidad de casos fue el NIC III (displasia severa). En los diagnósticos histológicos por sacabocado y cono existió correspondencia en todos los casos(AU)

Introduction: Radiosurgery aims to provide a diagnostic and treatment tool. Objectives: To describe the results of conization by radiosurgery in patients treated in the cervical pathology clinic of the institution. Methods: A descriptive cross-sectional investigation was carried out at Mártires del 9 de abril General Teaching Hospital, in Sagua la Grande, Villa Clara, Cuba. The study population consisted of 256 patients attended in the cervical pathology clinic who underwent conization by radiosurgery, from January 2013 to December 2015. For the collection of the information, the document review was used and a data collection form was made. Results: The preoperative diagnosis that contributed the greatest number of cases was IAS III (severe dysplasia) (78 cases; 30.5 percent). Conclusions: The premalignant lesions in the present study began to appear with a marked incidence from the age of 20 and up to 49, with the group of 30-39 years standing out. The increase in the number of sexual partners, as well as the early sexual intercourse increase the risk of suffering intraepithelial lesions in the cervix. After five years of beginning sexual intercourse, cervical intraepithelial lesions begin to appear, the preoperative diagnosis that contributed the greatest number of cases was IAS III (severe dysplasia). In histological diagnoses by punch and cone correspondence existed in all cases(AU)

Experiencia inicial de radioterapia estereotáxica (SBRT) en metástasis óseas de columna vertebral / Stereotactic body radiation therapy (SBRT) for pain management in spine bone metastases

Background: Treatment of spine bone metastases with stereotactic radio-therapy (SBRT) may produce greater pain relief than palliative radiotherapy. Aim: To evaluate the analgesic response to SBRT. Material and Methods: A search was made in an electronic database of all patients treated by SBRT in our center. We found 20 patients that were treated with SBRT in the spine on 24 sites (lesions). Analgesic response was evaluated at 3 and 6 months after SBRT. Other factors such as age, sex, functional status, diagnosis, metastasis location, dosimetry and toxicity of the treatment were also described. Results: The median follow-up was 8.1 months. Complete pain relief occurred at three months in 74% of the treated sites. At three months, 78% of the patients presented a functional status 0 (ECOG). The median dose used was 24 Gy in 2 fractions. No cases of G3 or greater toxicity were recorded. Conclusions: The analgesic response to SBRT seems to be better than that reported for palliative radiotherapy.

Gamma knife radiosurgery for trigeminal neuralgia: first case series from Latin America / Radiocirurgia por gamma knife para tratamento da neuralgia do trigêmeo: primeira série de casos na América Latina

ABSTRACT Gamma Knife® radiosurgery (GKRS) for trigeminal neuralgia is an effective treatment with at least a 50% reduction of pain in 75-95% of patients. Objective: To present the first series of patients treated for trigeminal neuralgia using GKRS in Latin America. Methods: Retrospective analysis. Analysis consisted of time to improvement of symptoms, best Barrow Neurological Institute scale (BNI) score after procedure, time without pain, time to recurrence and post-procedural hypoesthesia. Results: Nineteen cases of classical trigeminal neuralgia were analyzed and three cases of symptomatic trigeminal neuralgia were described. Mean time from symptom onset to radiosurgery was 99.6 months, and 78.9% of patients had undergone invasive procedures before treatment. Patients were followed for a mean of 21.7 months. BNI I was achieved in 36.8%, IIIa in 21.1%, IIIb in 21.1%, IV in 5.3% and V in 15.7%. New hypoesthesia developed in 12.1% patients, which was associated with achieving BNI I after the procedure (p < 0.05). Time from diagnosis to GKRS was higher in patients who failed to achieve BNI I (143 vs. 76 months). The distance from the root entry zone in patients who achieved BNI I was greater than patients who did not (1.94 vs. 1.14 mm). Mean distance from the root entry zone in patients with new hypoesthesia was 2.85 mm vs. 1.06 mm (p = 0.06). Conclusion: Clinical response to GKRS is related to the time between diagnosis and procedure, thus its indication should be considered early in the management of these patients.

RESUMO A radiocirurgia por Gamma Knife (GKRS) para neuralgia do trigêmeo é um tratamento comprovado, com redução de pelo menos 50% da dor em 75-95% dos casos. Objetivo: Apresentar a primeira série de pacientes tratados por neuralgia do trigêmeo com GKRS na America Latina. Métodos: Análise retrospectiva. A análise consistiu no tempo até melhora do sintoma, melhor escala do Barrow Neurological Institute (BNI) depois do procedimento, tempo sem dor, tempo até recorrência e hipoestesia pós-procedimento. Resultados: Dezenove casos de neuralgia do trigêmeo clássica foram analisados e três casos de neuralgia do trigêmeo sintomática foram descritos. Tempo médio entre começo dos sintomas e GKRS foi de 99,6 meses e 78,9% dos pacientes já tinham sido submetidos a procedimento invasivo prévio. O tempo de acompanhamento médio foi de 21,7 meses. BNI I foi conseguido em 36,8%, IIIa em 21,1%, IIIb em 21,1%, IV em 5,3% e V em 15,7%. Nova hipoestesia apareceu em 12,1% dos casos, o que foi associado a conseguir BNI I pós-procedimento (p < 0,05). Tempo desde o diagnóstico até GKRS foi maior em pacientes que não conseguiram BNI I (143 vs. 76 meses). Distância da zona de entrada do nervo em pacientes que conseguiram BNI I foi maior (1,94 vs. 1,14mm). Distância do zona de entrada do nervo em pacientes com nova hipoestesia foi de 2,85mm vs. 1,06mm (p = 0,06) Conclusão: A resposta à GKRS está relacionada ao tempo entre diagnóstico e procedimento, pelo que a indicação de GKRS deve ser considerada cedo no tratamento desses pacientes.

Long-term Survival in Patients Treated with a Robotic Radiosurgical Device for Liver Metastases / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The treatment of liver metastases with local procedures is a fast progressing field. For the most, long-term survival data is missing raising questions with regard to the efficacy of such modalities when compared to surgical resection. Radiosurgery using the CyberKnife device enables the treatment of liver lesions with a single-session approach. Here we present long-term survival data to explore the curative potential of this strategy. MATERIALS AND METHODS: Patients with oligo-metastatic disease limited to the liver have been treated with single-session or hypo-fractioned radiosurgery in curative intent and prospectively followed until death. Follow-up (FU) was performed using magnetic resonance imaging (MRI) 2 months after radiation and at 3-month intervals for the first 2 years. After that annual computed tomography or MRI scans were performed until 5 years post-treatment. Local recurrence in the radiated volume and recurrence outside the treated volume were used to define local and distant progression. Survival times were censored at the time of the last FU. RESULTS: One hundred twenty-six patients treated between 2005 and 2015 with 194 lesions were included into this study. Median FU was 30.0 months. According to Response Evaluation Criteria in Solid Tumors, 55.2% had a complete remission and 11.3% a partial remission. Seventy-two point two percent recurred outside the radiated lesion and median overall survival was 35.2 months with a 3-year survival rate of 47.7%. CONCLUSION: This is currently the largest cohort of stereotactic body radiation therapy treated liver lesions with a median long-term follow of 30 months. Robotic radiosurgery using a single session approach has a high efficacy to control the radiated lesion with the potential to cure patients.

A Case of Squamous Cell Carcinoma of the Bilateral External Auditory Canals / 대한이비인후과학회지

A malignant tumor of the external auditory canal (EAC) is a rare tumor, with a prevalence of between 1 and 6 people per 1 million population. Common symptoms of the EAC cancer include otorrhea, hearing loss, otalgia, or tinnitus, which are similar to symptoms of otitis media or otitis externa. Therefore, diagnosis may be delayed due to lack of EAC cancer-specific symptoms and the prognosis is also relatively poor despite intensive treatment. The most malignant tumor of the EAC is squamous cell carcinoma (SCC), which usully invades the ear unilaterally. SCC of bilateral EAC is extremely rare. We report here a rare case of bilateral EAC SCC. In this case, unilateral EAC SCC was treated via stereotactic radiosurgery and contralateral EAC SCC developed subsequently. This case implicates that radiosurgery can be a treatment option for EAC SCC but it may have carcinogenic effect. This case also shows that the ear should be examined bilaterally even when unilateral EAC cancer is encountered.

Stereotactic Radiosurgery for Dural Arteriovenous Fistulas Involving the Transverse-Sigmoid Sinus: A Single Center Experience and Review of the Literatures

OBJECTIVE: We retrospectively assessed the efficacy of stereotactic radiosurgery (SRS) for dural arteriovenous fistulas (DAVFs) involving the transverse-sigmoid sinus and analyzed the angiographic and clinical results with our 8-year experience.METHODS: Nine patients with intracranial DAVFs involving the transverse-sigmoid sinus underwent SRS using a Gamma Knife® (Elekta Inc., Atlanta, GA, USA) between 2009 and 2016. Five patients underwent SRS for residual DAVFs after embolization and four patients were treated with SRS alone. The median target volume was 1.9 cm3 (range, 0.8–14.2) and the median radiation dose of the target was 17 Gy (range, 16–20). The median follow-up period was 37 months (range, 7–81).RESULTS: Pulsating tinnitus (33%) was the most common symptom. DAVFs were completely obliterated in four patients (44%) and subtotally obliterated in five (56%). Six patients (67%) showed complete recovery of symptoms or signs, and three (33%) showed incomplete recovery. One patient experienced a recurrent seizure. Adverse radiation effects after SRS occurred in one patient (11%). The total obliteration rates after SRS were 16.7%, 37.5%, and 68.7% at 1, 2, and 3 years, respectively. The median interval from SRS to total obliteration of the fistula was 31 months (range, 12–38). The rates at which the symptoms started to improve were 40% at 1 month and 80% at 2 months after SRS. Symptoms started to improve at a median of 5 weeks after SRS (range, 3–21).CONCLUSION: SRS with or without embolization is a safe and effective treatment to relieve symptoms and obliterate DAVFs on the transverse-sigmoid sinus.

Quantitative Feasibility Evaluation of ¹¹C-Methionine Positron Emission Tomography Images in Gamma Knife Radiosurgery : Phantom-Based Study and Clinical Application

OBJECTIVE: The functional information of ¹¹C-methionine positron emission tomography (MET-PET) images can be applied for Gamma knife radiosurgery (GKR) and its image quality may affect defining the tumor. This study conducted the phantom-based evaluation for geometric accuracy and functional characteristic of diagnostic MET-PET image co-registered with stereotactic image in Leksell GammaPlan® (LGP) and also investigated clinical application of these images in metastatic brain tumors.METHODS: Two types of cylindrical acrylic phantoms fabricated in-house were used for this study : the phantom with an array-shaped axial rod insert and the phantom with different sized tube indicators. The phantoms were mounted on the stereotactic frame and scanned using computed tomography (CT), magnetic resonance imaging (MRI), and PET system. Three-dimensional coordinate values on co-registered MET-PET images were compared with those on stereotactic CT image in LGP. MET uptake values of different sized indicators inside phantom were evaluated. We also evaluated the CT and MRI co-registered stereotactic MET-PET images with MR-enhancing volume and PET-metabolic tumor volume (MTV) in 14 metastatic brain tumors.RESULTS: Imaging distortion of MET-PET was maintained stable at less than approximately 3% on mean value. There was no statistical difference in the geometric accuracy according to co-registered reference stereotactic images. In functional characteristic study for MET-PET image, the indicator on the lateral side of the phantom exhibited higher uptake than that on the medial side. This effect decreased as the size of the object increased. In 14 metastatic tumors, the median matching percentage between MR-enhancing volume and PET-MTV was 36.8% on PET/MR fusion images and 39.9% on PET/CT fusion images.CONCLUSION: The geometric accuracy of the diagnostic MET-PET co-registered with stereotactic MR in LGP is acceptable on phantom-based study. However, the MET-PET images could the limitations in providing exact stereotactic information in clinical study.