Nuestros investigadores

Luis Isaac Ramos García

Publicaciones científicas más recientes (desde 2010)

Autores: García, Marc; et al.
Revista: NATURE COMMUNICATIONS
ISSN 2041-1723  Vol. 10  Nº 1  2019  págs. 2235
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).
Autores: Diez Valle, Ricardo; Gállego, Jaime; et al.
Revista: PLOS ONE
ISSN 1932-6203  Vol. 14  Nº 6  2019  págs. e0217881
Background Hypofractionated radiation therapy is a feasible and safe treatment option in elderly and frail patients with glioblastoma. The aim of this study was to evaluate the effectiveness of hypofractionated radiation therapy with concurrent temozolomide in terms of feasibility and disease control in primary glioblastoma patients with poor prognostic factors other than advanced age, such as post-surgical neurological complications, high tumor burden, unresectable or multifocal lesions, and potential low treatment compliance due to social factors or rapidly progressive disease. Material and methods GTV included the surgical cavity plus disease visible in T1WI-MRI, FLAIR-MRI and in the MET-uptake. The CTV was defined as the GTV plus 1.5-2 cm margin; the PTV was the CTV+0.3 cm margin. Forty, fourty-five, and fifty grays in 15 fractions were prescribed to 95% of PTV, CTV, and GTV, respectively. Treatment was delivered using IMRT or the VMAT technique. Simultaneously, 75 mg/m(2)/day of temozolomide were administered. Results Between January 2010 and November 2017, we treated a total of 17 patients. The median age at diagnosis was 68-years; median KPS was 50-70%. MGMT-methylation status was negative in 5 patients, and 8 patients were IDH-wildtype. Eight of 18 patients were younger than 65-years. Median tumor volume was 26.95cc; median PTV volume was 322cc. Four lesions were unresectable; 6 patients underwent complete surgical resection. Median residual volume was 1.14cc. Progression-free survival was 60% at 6 months, 33% at 1-year and 13% at 2-years (median OS = 7 months). No acute grade 3-5 toxicities were documented. Symptomatic grade 3 radiation necrosis was observed in one patient. Conclusions Patients with poor clinical factors other than advanced age can be selected for hypofractionated radiotherapy. The OS and PFS rates obtained in our series are similar to those in patients treated with standard fractionation, assuring good treatment adherence, low rates of toxicity and probable improved cost-effectiveness.
Autores: Marigil, M. ; Aristu, José Javier; et al.
Revista: CANCER RESEARCH
ISSN 0008-5472  Vol. 78  Nº 13 Supl.  2018 
Autores: Arbea, Leire; et al.
Revista: NEURO-ONCOLOGY
ISSN 1522-8517  Vol. 20  Nº Supl. 3  2018  págs. 251 - 252
Autores: Garcia-Consuegra, A.; et al.
Revista: NEURO-ONCOLOGY
ISSN 1522-8517  Vol. 20  Nº Supl. 3  2018  págs. 253 - 253
Autores: Azorin, J.F.P.; Aguilar Redondo, P. B.; et al.
Revista: PHYSICS IN MEDICINE AND BIOLOGY
ISSN 0031-9155  Vol. 62  Nº 18  2017  págs. N417 - N427
In this study, we present a new procedure for the comparison of two dose matrices by means of a statistical test. A statistical distance is proposed to decide whether the difference between the two matrices is statistically significant. This statistical test is based on the square difference between the experimental and expected gamma matrix results. The expected gamma matrix is calculated by simulating the measurement process. For comparison purposes, the significance level of the test was chosen to give the same statistical significance as 90% of gamma-pass rate. The performance of the statistical distance is checked against 53 VMAT. The power of the presented test was compared using simulations with the 90% gamma-pass rate criteria for two cases in which intentional errors are introduced. In both cases, the test is uniformly more powerful. According to the test, two of the measured plans have a significant difference with calculated matrices, although the gamma pass rate measured was always greater than 90%.
Autores: Morán, Verónica; Prieto, Elena; Zubiria, A.; et al.
Revista: EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
ISSN 1619-7070  Vol. 43  Nº Supl 1  2016  págs. S410
Autores: Martínez-Monge, Rafael; Santisteban, Marta; et al.
Revista: BRACHYTHERAPY
ISSN 1538-4721  Vol. 14  Nº 4  2015  págs. 565 - 570
To determine whether the time to loading (TTL) affects locoregional control. METHODS AND MATERIALS: Locoregional control status was determined in 301 patients enrolled in several perioperative high-dose-rate brachytherapy (PHDRB) prospective studies conducted at the University of Navarre. The impact of the time elapsed from catheter implantation to the first PHDRB treatment (TTL) was analyzed. Patients treated with PHDRB alone (n = 113), mainly because of prior irradiation, received 32 Gy in eight twice-a-day treatments or 40 Gy in 10 twice-a-day treatments for negative or close/positive margins, respectively. Patients treated with PHDRB + external beam radiation therapy (EBRT) (n = 188) received 16 Gy in four twice-a-day treatments or 24 Gy in six twice-a-day treatments for negative or close/positive margins followed by 45 Gy of EBRT in 25 treatments. RESULTS: After a median followup of 6.5 years (range, 2-13.6+), 113 patients have failed (37.5%), 65 in the PHDRB-alone group (57.5%) and 48 in the combined PHDRB + EBRT group (25.5%). Patients who started PHDRB before Postoperative Day 5 had a 10-year locoregional control rate of 66.7% and patients who started PHDRB on Postoperative Day 5 or longer had a 10-year locoregional control rate of 51.8% (p = 0.009). Subgroup analysis detected that this difference was only observed in the recurrent cases treated with PHDRB alone (Subset 2; n = 99; p = 0.004). No correlation could be detected between locoregional control rate and TTL in the other patient subsets although a trend toward a decreased locoregional control rate after a longer TTL was observed when they were grouped together (p = 0.089). CONCLUSIONS: Patients should start PHDRB as soon as possible to maximize locoregional control especially in those recurrent cases treated with PHDRB alone. The time effect in other disease scenarios is less clear.
Autores: Cambeiro, Felix Mauricio, (Autor de correspondencia); Aristu, José Javier; Moreno, Marta; et al.
Revista: BRACHYTHERAPY
ISSN 1873-1449  Vol. 14  Nº 1  2015  págs. 62 - 70
Purpose: To assess the toxicity and efficacy of salvage wide resection (SWR) with intraoperative electron beam radiation therapy (IOERT) or perioperative high-dose-rate brachytherapy (PHDRB) in previously unirradiated patients (PUP) vs. previously irradiated patients (PIP) with isolated local recurrence of soft tissue sarcomas (STS) of the extremities and the superficial trunk. Methods and Materials: PUP received SWR and IOERT/PHDRB with external beam radiation therapy. PIP received SWR and IOERT/PHDRB only. Results: Fifty patients were analyzed retrospectively. PUP (. n= 24; 48%) received IOERT (. n= 13) or PHDRB (. n= 11). PIP (. n= 26; 52%) received IOERT (. n= 10) or PHDRB (. n= 16). Reintervention because of complications was not required in PUP. Nine of 26 (34%) PIP required reintervention (. p= 0.01). After a median followup of 3.7years (range, 0.2-18.3), the 5-year rates of locoregional control, distant control, and overall survival were 54%, 66%, and 56%, respectively. Five-year locoregional control was higher in PUP than in PIP (81% vs. 26%, p= 0.01) and in the extremity locations compared with trunk locations (68% vs. 28%, p= 0.001). Five-year overall survival was superior in unifocal vs. multifocal presentations (70% vs. 36%, p= 0.03) and for tumor sizes <4 vs. ¿4cm (74% vs. 50%, p= 0.05). Conclusions: Prior irradiation is the main determinant of locoregional control in patients with isolated local recurrence of STS. The locoregional control rates in PUP were similar to those described in primary STS. In PIP, SWR+IOERT/PHDRB reirradiation yielded modest locoregional control rates and was associated with significant morbidity, especially in PHDRB cases.
Autores: Martínez-Monge, Rafael, (Autor de correspondencia); Cambeiro, Felix Mauricio; et al.
Revista: BRACHYTHERAPY
ISSN 1538-4721  Vol. 13  Nº 4  2014  págs. 400 - 404
PURPOSE: To develop a simple clinical model predictive of locoregional failure after complete surgical resection followed by perioperative high-dose-rate brachytherapy (PHDRB) and external beam irradiation (EBRT). PATIENT AND METHODS: Patients (n=166) enrolled in several PHDRB prospective studies conducted at the University of Navarre were analyzed. PHDRB was given to total doses of 16 Gy/4 b.i.d. or 24 Gy/6 b.i.d. treatments for negative or close/positive margins along with 45Gy of EBRT. RESULTS: After a median followup of 7.4 years (range, 3-12+), 50 patients have failed and 116 remain controlled at last followup. Tumor size, with a cutoff point set at 3cm (p=0.041) and margin status (positive and <1mm vs. negative ¿1mm, p=0.0001) were independent predictors of locoregional control. These two parameters were used to develop a four-tiered, hierarchical scoring system that stratified patients into low-risk (negative ¿1mm margins and size ¿3cm), intermediate-risk (negative ¿1mm margins, and size >3cm), high-risk (positive and <1mm margins and size ¿3cm), and very high-risk categories (positive and <1mm margins and size >3cm). This classification yields 5-year locoregional control rates of 92.3%, 78.0%, 65.5%, and 48.0% for low-, intermediate-, high-, and very high-risk categories, respectively. The predictive ability of the model is highly significant (p=0.0001) with an area under the curve of 0.72 (0.64-0.81). CONCLUSIONS: The risk of locoregional failure after combined surgical resection, PHDRB, and EBRT is mainly determined by the number of residual clonogens, which is inversely proportional to the status of the surgical margins and directly related to the size of the resected tumor. These two parameters generate a four-tiered predictive model that seems to be valid for a number of different common tumors and clinical settings.
Autores: Pérez Azorin,JF; Marti-Climent, JM;
Revista: MEDICAL PHYSICS
ISSN 0094-2405  Vol. 41  Nº 6  2014  págs. 062101
The improved multichannel dosimetric method is able to remove many of the common disturbances usually present in radiochromic films and improves the gamma analysis results compared with the other three methods.
Autores: Martínez-Monge, Rafael; Cambeiro, Felix Mauricio; et al.
Revista: BRACHYTHERAPY
ISSN 1538-4721  Vol. 13  Nº 6  2014  págs. 591 - 596
PURPOSE: To determine whether perioperative high-dose-rate brachytherapy (PHDRB) implants with larger high-dose regions produce increased locoregional control. METHODS AND MATERIALS: Patients (n=166) enrolled in several PHDRB prospective studies conducted at the University of Navarre were analyzed. The PHDRB was given to total doses of 16Gy/4 b.i.d. or 24Gy/6 b.i.d. treatments for negative or close/positive margins along with 45Gy/25 Rx of external beam radiation therapy. The histogram-based generalized equivalent uniform dose (EUD) formulism was used to quantify and standardize the dose-volume histogram into 2-Gy equivalents. The region of interest analyzed included: tissue volume encompassed by the prescription isodose of 4Gy (TV100). Routine dose reporting parameters such as physical dose and single-point 2-Gy equivalent dose were used for reference. RESULTS: After a median followup of 7.4 years (range, 3-12+), 50 patients have failed, and 116 remain controlled at last followup. Overall, EUD was not different in the patients who failed compared with controls (89.1Gy vs. 86.5Gy; p=not significant). When patients were stratified by risk using the University of Navarre Predictive Model, very high-risk patients (i.e., tumors ¿3cm resected with close <1mm/positive margins) had an improved locoregional control with higher EUD values (p=0.028). This effect was not observed in low-, intermediate-, and high-risk University of Navarre Predictive Model categories. CONCLUSIONS: In very high-risk patients, enlarged high-dose regions can produce a dose-response effect. Routine dose reporting methods such as physical dose and single-point 2-Gy equivalent dose may not show this effect, but it can be revealed by histogram-based EUD assessment.
Autores: De Santiago, Ana; et al.
Revista: SUPPORT CARE CANCER
ISSN 0941-4355  Vol. 20  Nº 9  2012  págs. 2199 - 2203
ICS A significant number of patients were evaluated, many of them with severe symptoms and/or at the end of life. Inpatients receiving care from the PCCT experienced an improvement in symptom control within just a few days..
Autores: Arbea, Leire; Martínez-Monge, Rafael; Diaz-Gonzalez, JA; et al.
Revista: INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
ISSN 0360-3016  Vol. 83  Nº 2  2012  págs. 587-593
PURPOSE: To validate tolerance and pathological complete response rate (pCR) of a 4-week preoperative course of intensity-modulated radiation therapy (IMRT) with concurrent capecitabine and oxaliplatin (CAPOX) in patients with locally advanced rectal cancer. METHODS AND MATERIALS: Patients with T3 to T4 and/or N+ rectal cancer received preoperative IMRT (47.5 Gy in 19 fractions) with concurrent capecitabine (825 mg/m(2) b.i.d., Monday to Friday) and oxaliplatin (60 mg/m(2) on Days 1, 8, and 15). Surgery was scheduled 4 to 6 weeks after the completion of chemoradiation. Primary end points were toxicity and pathological response rate. Local control (LC), disease-free survival (DFS), and overall survival (OS) were also analyzed. RESULTS: A total of 100 patients were evaluated. Grade 1 to 2 proctitis was observed in 73 patients (73%). Grade 3 diarrhea occurred in 9% of the patients. Grade 3 proctitis in 18% of the first 50 patients led to reduction of the dose per fraction to 47.5 Gy in 20 treatments. The rate of Grade 3 proctitis decreased to 4% thereafter (odds ratio, 0.27). A total of 99 patients underwent surgery. A pCR was observed in 13% of the patients, major response (96-100% of histological response) in 48%, and pN downstaging in 78%. An R0 resection was performed in 97% of the patients. After a median follow-up of 55 months, the LC, DFS, and OS rates were 100%, 84%, and 87%, respectively. CONCLUSIONS: Preoperative CAPOX-IMRT therapy (47.5 Gy in 20 fractions) is feasible