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Lopez Guerra J.L.,Grupo IMO | Lopez Guerra J.L.,University of Seville | Marrone I.,Grupo IMO | Jaen J.,Grupo IMO | And 8 more authors.
Clinical and Translational Oncology | Year: 2014

Purpose: The objective of this study is to evaluate the tolerability and outcome of craniospinal irradiation (CSI) with helical tomotherapy (HT) in the treatment of medulloblastoma. Methods: We evaluated 19 consecutive patients with primary medulloblastoma who were treated with HT from 2007 through 2010. HT regimens to the neuroaxis included: 23.4 Gy at 1.8 Gy/fraction (N = 10), 36 Gy at 1.8 Gy/fraction (N = 7), and 39 Gy bid at 1.3 Gy/fraction (N = 2). The tumor bed received 54-60 Gy. Potential associations between patient, treatment, and toxicity factors and overall survival (OS) were assessed in univariate analyses using the Cox proportional hazards model. Spearman's rank correlation coefficient was used to correlate potential risk factors with the grade of acute toxicity. Results: The median age at diagnosis was 5 years (range 2-14) and the median follow-up for alive patients (N = 14) 40 months (range 10-62). Two- and three-year overall survival was 75 and 68 %, respectively. The most common acute toxicity was hematological (79 %), being grade 2 and grade 3 in 4 (21 %) and 11 (58 %) cases, respectively. No grade ≥2 late toxicities were observed. Higher grades of acute body toxicity were found in older children (P = 0.004). Longer time between diagnosis and radiation therapy was correlated with shorter OS (P = 0.03). In addition, higher grades of acute thrombocytopenia were associated with shorter OS (P = 0.03). Conclusions: CSI delivered with HT for medulloblastoma is well tolerated with low rates of severe acute toxicity. Further research is necessary to assess late toxicity with a longer follow-up. © 2013 Federación de Sociedades Españolas de Oncología (FESEO).

Pedrosa L.R.C.,Erasmus Medical Center | Van Hell A.,Netherlands Cancer Institute | Suss R.,Albert Ludwigs University of Freiburg | Van Blitterswijk W.J.,Netherlands Cancer Institute | And 7 more authors.
Pharmaceutical Research | Year: 2013

Purpose: To improve nanoliposomal-doxorubicin (DoxNL) delivery in tumor cells using liposome membrane-incorporated short-chain sphingolipids (SCS) with selective membrane-permeabilizing properties. DoxNL bilayers contained synthetic short-chain derivatives of known membrane microdomain-forming sphingolipids; C8-glucosylceramide (C8-GluCer), C8- galactosylceramide (C8-GalCer) or C8-lactosylceramide (C8-LacCer). Methods: DoxNL enriched with C8-GluCer or C8-GalCer were developed, optimized and characterized with regard to size, stability and drug retention. In vitro cytotoxic activity was studied in a panel of human tumor cell lines and normal cells. Intracellular Dox delivery was measured by flow cytometry and visualized by fluorescence microscopy. For a further understanding of the involved drug delivery mechanism confocal microscopy studies addressed the cellular fate of the nanoliposomes, the SCS and Dox in living cells. Results: C8-LacCer-DoxNL aggregated upon Dox loading. In tumor cell lines SCS-DoxNL with C8-GluCer or C 8-GalCer demonstrated strongly increased Dox delivery and cytotoxicity compared to standard DoxNL. Surprisingly, this effect was much less pronounced in normal cells. Nanoliposomes were not internalized, SCS however transfered from the nanoliposomal bilayer to the cell membrane and preceded cellular uptake and subsequent nuclear localization of Dox. Conclusion: C 8-GluCer or C8-GalCer incorporated in DoxNL selectively improved intracellular drug delivery upon transfer to tumor cell membranes by local enhancement of cell membrane permeability. © 2013 Springer Science+Business Media New York.

Lopez Guerra J.L.,Grupo IMO | Isa N.,Grupo IMO | Matute R.,Grupo IMO | Russo M.,Diego Portales University | And 9 more authors.
Clinical and Translational Oncology | Year: 2013

Background: The purpose of this study is to evaluate the tolerability of hypofractionated helical tomotherapy (HT) in the treatment of localized prostate cancer. Materials and methods: We evaluated 48 patients with primary adenocarcinoma of the prostate (cT1-T3N0M0) who were treated with hypofractionated HT from August 2008 through July 2011. Hypofractionated regimens included: 68.04 Gy at 2.52 Gy/fraction, 70 Gy at 2.5 Gy/fraction, and 70.2 Gy at 2.6 Gy/fraction. Genitourinary (GU) and gastrointestinal (GI) toxicity was scored using the Radiation Therapy Oncology Group scoring system. Results: Thirty-two patients were treated with 68.04 Gy, 5 patients with 70 Gy, and 11 with 70.2 Gy. The median age at diagnosis was 69 years (range 49-87) and the median follow-up 11 months (range 7-40). Grade 2 acute GI toxicity occurred in 9 patients (19 %). No grade 3 or higher acute GI toxicity was observed. Grade 2 and 3 acute GU toxicities occurred in 19 and 6 % of patients, respectively. The incidence of late grade 2 GI and GU toxicity was 4 and 2 %, respectively. No grade 3 or higher late toxicities were observed. Multivariate analysis showed that patients treated at 2.6 Gy/fraction or those who received a total radiation dose ≥70 Gy had higher rates of grade ≥2 acute GU toxicity (P = 0.004 and P = 0.048, respectively). Conclusion: Hypofractionated HT in the treatment of localized prostate cancer is well tolerated with no grade 3 or higher early or late GI and GU toxicities. Further research is needed to assess definitive late toxicity and tumor control. © 2012 Federación de Sociedades Españolas de Oncología (FESEO).

Sole C.V.,Grupo IMO | Lopez Guerra J.L.,Grupo IMO | Matute R.,Grupo IMO | Jaen J.,Grupo IMO | And 8 more authors.
Clinical and Translational Oncology | Year: 2013

Purpose: To investigate the outcomes and risk factors of patients treated with stereotactic ablative radiotherapy (SABR) delivered by image-guided helical tomotherapy (HT) for extracranial oligometastases. Methods: From August 2006 through July 2011, 42 consecutive patients (median age 69 years [range 16-87]) with oligometastases (≤3) received HT to all known cancer sites (lung, n = 28; liver, n = 12; adrenal, n = 2). Prognostic factors were assessed by Cox's proportional hazards regression analysis. Results: A total of 60 lesions were treated with hypofractionated HT (median dose 39 Gy [range 36-72.5]; median dose per fraction 12 Gy [range 5-20]). Complete or partial response was observed in 40 (54 %) patients. With a median follow-up period of 15 months, 1- and 2-year overall survival (OS) was 84 and 63 %, respectively; and 1- and 2-year local control (LC) was 92 and 86 %, respectively. Four patients had pneumonitis Grade ≥2 and two patients had lower gastrointestinal toxicity Grade ≥2. Only the lack of complete/partial response was associated with higher risk of mortality on univariate (HR = 3.8, P = 0.04) and multivariate (HR = 6.6, P = 0.01) analyses. Conclusions: SABR delivered by image-guided HT is well tolerated and offers adequate LC with low acute morbidity in patients with extracranial oligometastatic disease. We found that the response to HT was the only predictor for OS. © 2012 Federación de Sociedades Españolas de Oncología (FESEO).

Loading Institute Of Cancerologie Gustave Roussy Villejuif collaborators
Loading Institute Of Cancerologie Gustave Roussy Villejuif collaborators