What is the best term in Spanish to express the concept of cancer-related fatigue?

Introduction: Fatigue is one of the most frequent symptoms in patients with cancer. No adequate term in Spanish has been defined to describe the English concept of fatigue. Aim: To identify the most suitable Spanish words that define the concept of fatigue and to check psychometric characteristics. Method: Consensus with professional experts on Spanish words that best suit the English concept of fatigue. A prospective study on oncologic patients was also undertaken, which included an evaluation of the intensity of fatigue through visual numeric scales (VNS) where the words had been previously selected. The fatigue subscale of the Functional Assessment of Cancer Therapy-Fatigue (FACT-F) questionnaire was taken as a reference. Results: The experts highlighted the words cansancio, agotamiento, and debilidad (tiredness, exhaustion, and weakness) as the terms that best defined the concept of fatigue. In the psychometric assessment study, 100 patients were included, of which 61 (61%) presented diagnostic values for cancer-related fatigue in the FACT-F fatigue subscale (score 34/52 or lower). The VNS for the chosen terms obtained a high correlation with the FACT-F fatigue subscale results: cansancio (tiredness) r = −0.71, agotamiento (exhaustion) r = −0.74, debilidad (weakness) r = −0.74, with no statistical differences between them. For the detection of fatigue by means of the VNS, tiredness (cutoff point ≥4/10) gave sensitivity (S) 0.90 and specificity (E) 0.72; exhaustion (cutoff point ≥3/10) S 0.95 and E 0.90 and weakness (cutoff point ≥4/10) S 0.92 and E 0.72. The ROC curve was 0.88 for tiredness, 0.94 for exhaustion, and 0.92 for weakness, with no significant difference between the areas mentioned. The terms cansancio, agotamiento, and debilidad (tiredness, exhaustion, and weakness) are suitable for defining the English concept of fatigue in Spanish, and should be the preferred option for inclusion in evaluation tools

Dose volume histogram constraints in patients with soft tissue sarcomas of the extremities and the superficial trunk treated with surgery and perioperative HDR brachytherapy

Background: Wound healing complications (WHC), osteoradionecrosis (ORN), and nerve damage (ND) are common adverse effects in adult patients with soft tissue sarcomas of the extremities and the superficial trunk treated with surgery and perioperative high dose rate brachytherapy (PHDRB) alone or combined with external beam radiotherapy (EBRT). Rationale: Analysis of the treatment factors contributing to these complications can potentially minimize their occurrence and severity. Patients: A total of 169 patients enrolled in two parallel prospective studies were included in this analysis. Previously Unirradiated cases (Group 1; n = 139) were treated with surgical resection, 16–24 Gy of PHDRB and 45 Gy of EBRT. Adjuvant chemotherapy was given to selected patients with high-grade tumors. Previously irradiated cases (Group 2; n = 30) were treated with surgical resection and 32– 40 Gy of PHDRB without further EBRT. Methods: Patient factors, tumor factors, surgical factors, PHDRB factors and EBRT factors were analyzed using Cox univariate and multivariate analysis. Results: In Previously Unirradiated cases, WHC, ORN and ND occurred in 38.8%, 5.0% and 19.4%. Multivariate analysis indicated that WHC increased with CTV size (p = 0.02) and CTV2cm3 Physical dose (p = 0.02). ORN increased with Bone2cm3 EQD2 67 Gy (p = 0.01) and ND was more frequent in patients with TV100 DVH-based dose (tissue volume encompassed by the 100% isodose) 84 Gy (p < 0.01). In Previously Irradiated cases, WHC, ORN and ND occurred in 63.3%, 3.3% and 23.3%. Multivariate analysis showed that WHC was more frequent in patients with Skin2cm3 Lifetime EQD2 84 Gy (p = 0.01) and ND was more frequent after CTVD90 Physical Doses 40 Gy (p < 0.01). Conclusions: WHC in Previously Unirradiated patients can be minimized by using a more conservative CTV definition together with a meticulous implant technique and planning aimed to minimize hyperdose CTV2cm3 areas. In Previously Irradiated patients WHC may be mimimized considering Lifetime EQD2 Skin2cm3 doses. ORN can be reduced by using the Bone2cm3 EQD2 constraint. ND occurs more frequently in patients with large tumors receiving high treated volume doses, but no specific constraints can be recommended due to the lack of peripheral nerve definition during brachytherapy planning

Radioterapia estereotáctica

La radioterapia con técnica estereotáctica es una modalidad de radioterapia externa que utiliza un sistema de coordenadas tridimensionales independientes del paciente para la localización precisa de la lesión. También se caracteriza porque los haces de irradiación son altamente conformados, precisos y convergentes sobre la lesión que hacen posible la administración de dosis muy altas de radioterapia sin incrementar la irradiación de los órganos o estructuras sanas adyacentes. Cuando el procedimiento se realiza en una sesión de tratamiento se denomina radiocirugía y si se administra en varias sesiones se denomina radioterapia estereotáctica. Se precisa de sistemas de fijación e inmovilización del paciente especiales (guías o marcos estereotácticos) y dispositivos de radioterapia capaces de generar haces muy conformados (acelerador lineal, gammaknife, cyberknife, tomoterapia, ciclotrones). La radioterapia estereotáctica moderna utiliza marcas radioopacas intratumorales o sistemas de imágenes de TAC incluidos en el dispositivo de irradiación, que permiten una precisa localización de las lesiones móviles en cada sesión de tratamiento. Además, los avances tecnológicos hacen posible coordinar los movimientos de la lesión en la respiración con la unidad de radioterapia (gaiting y tracking) de forma que pueden estrecharse al máximo los márgenes y por lo tanto excluir un mayor volumen de tejido sano La radiocirugía está indicada principalmente en lesiones cerebrales benignas o malignas menores de 3-4 centímetros (malformaciones arteriovenosas, neurinomas, meningiomas, metástasis cerebrales) y la radioterapia estereotáctica se administra fundamentalmente en tumores de localización extracraneal que requieran una alta conformación y precisión como cáncer precoz de pulmón inoperable y metástasis hepáticas.Stereotactic radiotherapy is an external radiation modality that uses a system of three dimensional references independent of the patient to achive a precise location of the lesion. Stereotactic radiotherapy generate highly conformal, precisely focused radiation beams to administer very high doses of radiation without increasing the radiation to healthy surrounding organs or structures. When the procedure is carried out in one treatment session the procedure is termed radiosurgery, and when the treatment is administered in several fractions, the radiation modality is termed stereotactic radiotherapy. Special systems of patient immobilization (guides or stereotactic frames) are required together with radiotherapy devices capable of generating conformal beams (lineal accelerator, gammaknife, cyberknife, tomotherapy, cyclotrons). Modern stereotactic radiotherapy techniques employ intratumoural radio-opaque fiducials or CT image systems included in the irradiation device, which make possible a precise location of mobile lesions in each treatment session. Besides, technological advances permit breathing synchronized radiation (gating and tracking) for maximum tightening of margins and excluding a greater volume of healthy tissue. Radiosurgery is mainly indicated in benign or malign cerebral lesions less than 3-4 centimetres (arteriovenous malformations, neurinomas, meningiomas, cerebral metastases) and stereotactic radiotherapy is basically administered in tumours of extracraneal location that require high conformation and precision, such as inoperable early lung cancer and liver metastasis

Delta-24-RGD combined with radiotherapy exerts a potent antitumor effect in diffuse intrinsic pontine glioma and pediatric high grade glioma models

Pediatric high grade gliomas (pHGG), including diffuse intrinsic pontine gliomas (DIPGs), are aggressive tumors with a dismal outcome. Radiotherapy (RT) is part of the standard of care of these tumors; however, radiotherapy only leads to a transient clinical improvement. Delta-24-RGD is a genetically engineered tumor-selective adenovirus that has shown safety and clinical efficacy in adults with recurrent gliomas. In this work, we evaluated the feasibility, safety and therapeutic efficacy of Delta-24-RGD in combination with radiotherapy in pHGGs and DIPGs models. Our results showed that the combination of Delta-24-RGD with radiotherapy was feasible and resulted in a synergistic anti-glioma effect in vitro and in vivo in pHGG and DIPG models. Interestingly, Delta-24-RGD treatment led to the downregulation of relevant DNA damage repair proteins, further sensitizing tumors cells to the effect of radiotherapy. Additionally, Delta-24-RGD/radiotherapy treatment significantly increased the trafficking of immune cells (CD3, CD4+ and CD8+) to the tumor niche compared with single treatments. In summary, administration of the Delta-24-RGD/radiotherapy combination to pHGG and DIPG models is safe and significantly increases the overall survival of mice bearing these tumors. Our data offer a rationale for the combination Delta-24-RGD/radiotherapy as a therapeutic option for children with these tumors. SIGNIFICANCE: Delta-24-RGD/radiotherapy administration is safe and significantly increases the survival of treated mice. These positive data underscore the urge to translate this approach to the clinical treatment of children with pHGG and DIPGs

The oncolytic virus Delta-24-RGD elicits an antitumor effect in pediatric glioma and DIPG mouse models

Pediatric high-grade glioma (pHGG) and diffuse intrinsic pontine gliomas (DIPGs) are aggressive pediatric brain tumors in desperate need of a curative treatment. Oncolytic virotherapy is emerging as a solid therapeutic approach. Delta-24-RGD is a replication competent adenovirus engineered to replicate in tumor cells with an aberrant RB pathway. This virus has proven to be safe and effective in adult gliomas. Here we report that the administration of Delta-24-RGD is safe in mice and results in a significant increase in survival in immunodeficient and immunocompetent models of pHGG and DIPGs. Our results show that the Delta-24-RGD antiglioma effect is mediated by the oncolytic effect and the immune response elicited against the tumor. Altogether, our data highlight the potential of this virus as treatment for patients with these tumors. Of clinical significance, these data have led to the start of a phase I/II clinical trial at our institution for newly diagnosed DIPG (NCT03178032)

Dosimetría y control de calidad con películas radiocrómicas en radioterapia externa

El objetivo de la radioterapia es administrar una dosis de radiación letal a los tejidos diana minimizando la que llega a los tejidos sanos (órganos de riesgo), siendo ésta última básicamente la responsable de los efectos secundarios del tratamiento radioterápico y la que impone los límites de dosis alcanzables en las lesiones. Por esta razón, la distribución de dosis en el paciente y su incertidumbre es un factor crítico a la hora de programar y evaluar un tratamiento. Hoy día, la implantación de la radiografía digital y la retirada de las reveladoras han hecho inviable el uso de estos dosímetros y ha potenciado el uso de las películas radiocrómicas que, al igual que las radiográficas, poseen una buena resolución espacial pero que no necesitan revelado. Unido a esto, las películas radiocrómicas poseen un número atómico efectivo parecido al del agua, lo que las hacen practicante equivalentes a tejido y además pueden usarse directamente en agua. El objetivo de la presente memoria será investigar el empleo de las películas radiocrómicas en el contexto de la verificación de tratamientos complejos de radioterapia, proponiendo un nuevo método de calibración y mejorando las técnicas y los procedimientos que se usan en dosimetría a través de un nuevo método dosimétrico multicanal. Al mismo tiempo, y de forma alternativa al método dosimétrico clásico, se propone un sencillo método dosimétrico basado en las propiedades ópticas de las películas radiocrómicas

Dosimetría y control de calidad con películas radiocrómicas en radioterapia externa

El objetivo de la radioterapia es administrar una dosis de radiación letal a los tejidos diana minimizando la que llega a los tejidos sanos (órganos de riesgo), siendo ésta última básicamente la responsable de los efectos secundarios del tratamiento radioterápico y la que impone los límites de dosis alcanzables en las lesiones. Por esta razón, la distribución de dosis en el paciente y su incertidumbre es un factor crítico a la hora de programar y evaluar un tratamiento. Hoy día, la implantación de la radiografía digital y la retirada de las reveladoras han hecho inviable el uso de estos dosímetros y ha potenciado el uso de las películas radiocrómicas que, al igual que las radiográficas, poseen una buena resolución espacial pero que no necesitan revelado. Unido a esto, las películas radiocrómicas poseen un número atómico efectivo parecido al del agua, lo que las hacen practicante equivalentes a tejido y además pueden usarse directamente en agua. El objetivo de la presente memoria será investigar el empleo de las películas radiocrómicas en el contexto de la verificación de tratamientos complejos de radioterapia, proponiendo un nuevo método de calibración y mejorando las técnicas y los procedimientos que se usan en dosimetría a través de un nuevo método dosimétrico multicanal. Al mismo tiempo, y de forma alternativa al método dosimétrico clásico, se propone un sencillo método dosimétrico basado en las propiedades ópticas de las películas radiocrómicas

Intensity-modulated radiation therapy (IMRT) vs. 3D conformal radiotherapy (3DCRT) in locally advanced rectal cancer (LARC): dosimetric comparison and clinical implications

Purpose: To compare target dose distribution, comformality, normal tissue avoidance, and irradiated body volume (IBV) in 3DCRT using classic anatomical landmarks (c3DCRT), 3DCRT fitting the PTV (f3DCRT), and intensitymodulated radiation therapy (IMRT) in patients with locally advanced rectal cancer (LARC). Materials and methods: Fifteen patients with LARC underwent c3DCRT, f3DCRT, and IMRT planning. Target definition followed the recommendations of the ICRU reports No. 50 and 62. OAR (SB and bladder) constraints were D5 ≤ 50 Gy and Dmax < 55 Gy. PTV dose prescription was defined as PTV95 ≥ 45 Gy and PTVmin ≥ 35 Gy. Target coverage was evaluated with the D95, Dmin, and Dmax. Target dose distribution and comformality was evaluated with the homogeneity indices (HI) and Conformity Index (CI). Normal tissue avoidance of OAR was evaluated with the D5 and V40. IBV at 5 Gy (V5), 10 Gy (V10), and 20 Gy (V20) were calculated. Results: The mean GTV95, CTV95, and PTV95 doses were significantly lower for IMRT plans. Target dose distribution was more inhomogeneous after IMRT planning and 3DCRTplans had significantly lower CI. The V40 and D5 values for OAR were significantly reduced in the IMRT plans .V5 was greater for IMRT than for f3DCRT planning (p < 0.05) and V20 was smaller for IMRT plans(p < 0.05). Conclusions: IMRT planning improves target conformity and decreases irradiation of the OAR at the expense of increased target heterogeneity. IMRT planning increases the IBV at 5 Gy or less but decreases the IBV at 20 Gy or more

What is the best term in Spanish to express the concept of cancer-related fatigue?

Introduction: Fatigue is one of the most frequent symptoms in patients with cancer. No adequate term in Spanish has been defined to describe the English concept of fatigue. Aim: To identify the most suitable Spanish words that define the concept of fatigue and to check psychometric characteristics. Method: Consensus with professional experts on Spanish words that best suit the English concept of fatigue. A prospective study on oncologic patients was also undertaken, which included an evaluation of the intensity of fatigue through visual numeric scales (VNS) where the words had been previously selected. The fatigue subscale of the Functional Assessment of Cancer Therapy-Fatigue (FACT-F) questionnaire was taken as a reference. Results: The experts highlighted the words cansancio, agotamiento, and debilidad (tiredness, exhaustion, and weakness) as the terms that best defined the concept of fatigue. In the psychometric assessment study, 100 patients were included, of which 61 (61%) presented diagnostic values for cancer-related fatigue in the FACT-F fatigue subscale (score 34/52 or lower). The VNS for the chosen terms obtained a high correlation with the FACT-F fatigue subscale results: cansancio (tiredness) r = −0.71, agotamiento (exhaustion) r = −0.74, debilidad (weakness) r = −0.74, with no statistical differences between them. For the detection of fatigue by means of the VNS, tiredness (cutoff point ≥4/10) gave sensitivity (S) 0.90 and specificity (E) 0.72; exhaustion (cutoff point ≥3/10) S 0.95 and E 0.90 and weakness (cutoff point ≥4/10) S 0.92 and E 0.72. The ROC curve was 0.88 for tiredness, 0.94 for exhaustion, and 0.92 for weakness, with no significant difference between the areas mentioned. The terms cansancio, agotamiento, and debilidad (tiredness, exhaustion, and weakness) are suitable for defining the English concept of fatigue in Spanish, and should be the preferred option for inclusion in evaluation tools

Bone-marrow-derived cell differentiation into microglia: a study in a progressive mouse model of Parkinson's disease

The migration of peripheral bone-marrow-derived cells (BMDCs) to the brain was studied in a chronic mouse model of Parkinson's disease (PD). BMDCs expressing the enhanced green fluorescent protein (GFP) were aseptically obtained from C57 BL/6-EGFP-Tg mice and intravenously injected into C57 BL/6j mice which had received a total body irradiation of 8 Gy to induce bone marrow ablation. Implanted GFP-BMDCs replenished the bone marrow of irradiated mice, and progressively crossed the blood-brain barrier (BBB), penetrating different mesencephalic and telencephalic brain regions in the following months. The progressive degeneration of dopamine (DA) cells with a small daily dose (4 mg/kg/day for 20 days) of 1-methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine (MPTP) increased the penetration of GFP-BMDCs into the brain, particularly into those regions with marked DA innervation and which showed the clearest DA cell loss. BMDC penetration increased before the DA cell loss was evident and persisted for a long time after MPTP withdrawal. Under these conditions, most BMDCs differentiated into microglia (CD68 expression was observed in 50% of GFP cells 60 days after MPTP administration). BMDC-derived microglia showed morphological characteristics of cell activation, with the glial cell line-derived neurotrophic factor only being expressed in 3% of the cells. No differentiation into neurons (NeuN expression), astrocites (GFAP), cytotoxic lymphocytes (CD8) and T-helper lymphocytes (CD4) was observed. Taken together, the present data suggest that a significant portion of microglial cells is of a peripheral origin. Bearing in mind that microglial reaction is a significant part of the degenerative process in PD, the increase of BMDC penetration into DA-rich areas during DA cell degeneration and their differentiation into microglia suggest that cells coming across the BBB may participate in the neurodegeneration process. The precise role of such a cell inflow into the brain requires further study. Nevertheless, this may represent an opportunity to develop neuroprotective therapeutic strategies for PD