Publications by authors named "Salvador Villa"

56 Publications

Results of the IROCA international clinical audit in prostate cancer radiotherapy at six comprehensive cancer centres.

Sci Rep 2021 Jun 10;11(1):12323. Epub 2021 Jun 10.

Department of Electroradiology, Poznan University of Medical Sciences, Poznan, Poland.

To assess adherence to standard clinical practice for the diagnosis and treatment of patients undergoing prostate cancer (PCa) radiotherapy in four European countries using clinical audits as part of the international IROCA project. Multi-institutional, retrospective cohort study of 240 randomly-selected patients treated for PCa (n = 40/centre) in the year 2015 at six European hospitals. Clinical indicators applicable to general and PCa-specific radiotherapy processes were evaluated. All data were obtained directly from medical records. The audits were performed in the year 2017. Adherence to clinical protocols and practices was satisfactory, but with substantial inter-centre variability in numerous variables, as follows: staging MRI (range 27.5-87.5% of cases); presentation to multidisciplinary tumour board (2.5-100%); time elapsed between initial visit to the radiation oncology department and treatment initiation (42-102.5 days); number of treatment interruptions ≥ 1 day (7.5-97.5%). The most common deviation from standard clinical practice was inconsistent data registration, mainly failure to report data related to diagnosis, treatment, and/or adverse events. This clinical audit detected substantial inter-centre variability in adherence to standard clinical practice, most notably inconsistent record keeping. These findings confirm the value of performing clinical audits to detect deviations from standard clinical practices and procedures.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-91723-0DOI Listing
June 2021

Prospective pilot study to explore the melatonin level in brain tumor patients undergoing radiotherapy.

Sleep Breath 2021 Apr 6. Epub 2021 Apr 6.

Radiation Oncology Department, Catalan Institute of Oncology (ICO), Badalona (Barcelona), Catalonia, Spain.

Purpose: Our aim was to assess if the radiotherapy dose decreased the melatonin levels as well as the quality of life and sleep in brain tumor patients.

Methods: We performed a follow-up study on melatonin levels in saliva and its urinary metabolite sulfatoxi-melatonine (STM) samples in patients with brain tumors treated with radiotherapy close to the pineal gland's area. We analyzed the cortisol, cortisone, and excrection of STM normalized by urinary creatinine. In some cases, a polysomnography (PSG) was performed. Quality of life questionnaires, distress scale, and sleepiness inventories were also administered.

Results: We included twelve patients (experimental arm) and eight healthy controls (control group). No differences were observed between experimental arm and control group at baseline. No differences were detected in the experimental arm before and after delivering the radiotherapy. No clinically significant differences were found according to the radiotherapy dose delivered.

Conclusion: Melatonin levels and PSG outcomes do not change after receiving radiotherapy. The findings of this study do not show a statistically significant association between the treatment and the quality of life and sleep.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11325-021-02365-5DOI Listing
April 2021

RNA sequencing and Immunohistochemistry Reveal as a Stronger Marker of Survival than Molecular Subtypes in G-CIMP-negative Glioblastoma.

Clin Cancer Res 2021 Jan 26;27(2):645-655. Epub 2020 Oct 26.

Glioma and Neural Stem Cell Group, Translational Genomics and Targeted Therapeutics in Solid Tumors Team, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain.

Purpose: Glioblastoma is the most aggressive brain tumor in adults and has few therapeutic options. The study of molecular subtype classifications may lead to improved prognostic classification and identification of new therapeutic targets. The Cancer Genome Atlas (TCGA) subtype classification has mainly been applied in U.S. clinical trials, while the intrinsic glioma subtype (IGS) has mainly been applied in European trials.

Experimental Design: From paraffin-embedded tumor samples of 432 patients with uniformly treated, newly diagnosed glioblastoma, we built tissue microarrays for IHC analysis and applied RNA sequencing to the best samples to classify them according to TCGA and IGS subtypes.

Results: We obtained transcriptomic results from 124 patients. There was a lack of agreement among the three TCGA classificatory algorithms employed, which was not solely attributable to intratumoral heterogeneity. There was overlapping of TCGA mesenchymal subtype with IGS cluster 23 and of TCGA classical subtype with IGS cluster 18. Molecular subtypes were not associated with prognosis, but levels of expression of 13 novel genes were identified as independent prognostic markers in glioma-CpG island methylator phenotype-negative patients, independently of clinical factors and methylation. These findings were validated in at least one external database. Three of the 13 genes were selected for IHC validation. In particular, high RNA expression and low ZNF7 protein expression were strongly associated with longer survival, independently of molecular subtypes.

Conclusions: TCGA and IGS molecular classifications of glioblastoma have no higher prognostic value than individual genes and should be refined before being applied to clinical trials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1078-0432.CCR-20-2141DOI Listing
January 2021

A phase II randomized, multicenter, open-label trial of continuing adjuvant temozolomide beyond 6 cycles in patients with glioblastoma (GEINO 14-01).

Neuro Oncol 2020 12;22(12):1851-1861

Pathology Service, Hospital Universitari Germans Trias i Pujol, Badalona, Spain.

Background: Standard treatment for glioblastoma is radiation with concomitant and adjuvant temozolomide for 6 cycles, although the optimal number of cycles of adjuvant temozolomide has long been a subject of debate. We performed a phase II randomized trial investigating whether extending adjuvant temozolomide for more than 6 cycles improved outcome.

Methods: Glioblastoma patients treated at 20 Spanish hospitals who had not progressed after 6 cycles of adjuvant temozolomide were centrally randomized to stop (control arm) or continue (experimental arm) temozolomide up to a total of 12 cycles at the same doses they were receiving in cycle 6. Patients were stratified by MGMT methylation and measurable disease. The primary endpoint was differences in 6-month progression-free survival (PFS). Secondary endpoints were PFS, overall survival (OS), and safety (Clinicaltrials.gov NCT02209948).

Results: From August 2014 to November 2018, 166 patients were screened, 7 of whom were ineligible. Seventy-nine patients were included in the stop arm and 80 in the experimental arm. All patients were included in the analyses of outcomes and of safety. There were no differences in 6-month PFS (control 55.7%; experimental 61.3%), PFS, or OS between arms. MGMT methylation and absence of measurable disease were independent factors of better outcome. Patients in the experimental arm had more lymphopenia (P < 0.001), thrombocytopenia (P < 0.001), and nausea and vomiting (P = 0.001).

Conclusions: Continuing temozolomide after 6 adjuvant cycles is associated with greater toxicity but confers no additional benefit in 6-month PFS.

Key Points: 1. Extending adjuvant temozolomide to 12 cycles did not improve 6-month PFS.2. Extending adjuvant temozolomide did not improve PFS or OS in any patient subset.3. Extending adjuvant temozolomide was linked to increased toxicities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/neuonc/noaa107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746946PMC
December 2020

Breast Cancer Patient with Li-Fraumeni Syndrome: A Case Report Highlighting the Importance of Multidisciplinary Management.

Case Rep Oncol 2020 Jan-Apr;13(1):130-138. Epub 2020 Feb 13.

Medical Oncology Department, Badalona Applied Research Group in Oncology (B-ARGO Group), Catalan Institute of Oncology, Badalona, Spain.

Germline mutations in TP53, a tumor suppressor gene, are involved in the development of Li-Fraumeni syndrome, a rare disorder that predisposes carriers to multiple tumors. TP53 mutations have been associated with resistance to treatment and poor prognosis. A young female with the pathogenic germline TP53 mutation c.844C > T (p.R282W) was diagnosed with two metachronous breast tumors, one HER2-negative and the other HER2-positive. She was later diagnosed with synchronous glioblastoma, epidermal growth factor receptor-mutated lung adenocarcinoma, and HER2-negative breast cancer metastases. The patient was treated with local therapies, including brain surgery and radiotherapy, lung surgery, and a bilateral mastectomy, as well as with targeted systemic treatment. She proved to be highly sensitive to systemic therapy, and 13 years after the initial diagnosis of breast cancer and 6 years after the diagnosis of the two new primary tumors and recurrence of a prior cancer, she is alive with an excellent performance status. This surprising positive evolution may well be partly due to the pronged multidisciplinary approach to managing her disease and her extraordinary response to treatment: the lung adenocarcinoma showed excellent response to erlotinib; the breast cancer responded extremely well to eribulin and pegylated liposomal doxorubicin; and the glioblastoma has remained in response to surgery and radiotherapy. Despite harboring a TP53 mutation and having multiple tumors, this patient has shown an unexpectedly favorable evolution. The coordinated participation of a multidisciplinary team and the patient's own extraordinarily high sensitivity to systemic treatment played a major role in this evolution.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000505684DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7098344PMC
February 2020

A Case about the Upgrade of Manufacturing Equipment for Insertion into an Industry 4.0 Environment.

Sensors (Basel) 2019 Jul 27;19(15). Epub 2019 Jul 27.

Tecnologico de Monterrey, Escuela de Ingeniería y Ciencias, Ave. Eugenio Garza Sada 2501, Monterrey 64849, Mexico.

Industry 4.0 is a synonym for the confluence of technologies that allows the integration of information technology, data science, and automated equipment, to produce smart industrial systems. The process of inserting new technologies into current conventional environments involves a wide range of disciplines and approaches. This article presents the process that was followed to identify and upgrade one station in an industrial workshop to make it compatible with the more extensive system as it evolves into the Industry 4.0 environment. An information processing kit was developed to upgrade the equipment from an automated machine to an Industry 4.0 station. The kit includes a structure to support the sensor and the data processing unit; this unit consisted of a minicomputer that records the data, graded the performance of the components, and sent the data to the cloud for storage, reporting, and further analysis. The information processing kit allowed the monitoring of the inspection system and improved the quality and speed of the inspection process.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/s19153304DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6696624PMC
July 2019

Primary extranodal lymphoma of the glands. Literature review and options for best practice in 2019.

Crit Rev Oncol Hematol 2019 Mar 18;135:8-19. Epub 2019 Jan 18.

APHP, Henri Mondor University Hospital, Department of Radiation Oncology and Henri Mondor Breast Center, University of Paris - Est Créteil (UPEC), INSERM, U955 Eq07, Créteil, France.

Primary extranodal non-Hodgkin's lymphomas (EN-NHL) are a heterogeneous group of malignancies that involve numerous entities with significant difference in terms of tumor site locations, prognostic factors, biology expression, and therapeutic options. In the literature, many EN-NHL types were reported from limited series which only allowed narrow views for elucidating prognostic factors and defining the role of loco-regional therapies in the era of new systemic and biologically targeted therapies. The Rare Cancer Network (RCN), an international multidisciplinary consortium, has published a number of reports on several EN-NHL sites which included many gland locations. In this review, we will focus on the recent literature for a selected number of EN-NHL types in both exocrine and endocrine gland locations. We aim to provide renewed and clear messages for the best practice in 2019 for diagnosis, histopathology, treatments, and also their prognostic implications. We believe that better understanding of molecular and genetic characteristics of these particular diseases is crucial for an appropriate management in the era of personalized treatment developments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.critrevonc.2019.01.005DOI Listing
March 2019

Paraganglioma of the head and neck region, treated with radiation therapy, a Rare Cancer Network study.

Head Neck 2019 06 11;41(6):1770-1776. Epub 2019 Jan 11.

Radiation Oncology Department, Centre Francois Baclesse, Caen, France.

Background: Paraganglioma of the head and neck (HNPGL) are rare often benign tumors. Surgery and radiation therapy (RT) are the main treatment choices. We present an analysis of outcome and toxicity after RT from 13 institutions of the Rare Cancer Network.

Methods: Data were collected using a questionnaire concerning patients' characteristics, treatment, and outcome. A total of 81 patients with 82 HNPGL were analyzed.

Results: The median follow-up was 48 months (1-456). Sixty-two lesions were treated with conventional RT and 20 lesions with stereotactic RT. Local control (LC) was achieved in 69 out of 77 lesions. Late toxicity occurred in 17 patients. Patients treated with stereotactic RT experienced neither disease progression nor late toxicity. Four patients with a follow-up longer than 20 years experienced disease progression.

Conclusion: RT for HNPGL offered good local control with acceptable toxicity. Stereotactic RT might offer better results. Long-term follow-up is required.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hed.25611DOI Listing
June 2019

Association between EBRT dose volume histograms and quality of life in prostate cancer patients.

Rep Pract Oncol Radiother 2018 Sep-Oct;23(5):360-368. Epub 2018 Aug 13.

Institut Català d'Oncologia (ICO), L'Hospitalet, Barcelona, Spain.

Aim: To evaluate the association between dose-volume histogram (DVH) values in organs at risk (OAR) and patient-reported HRQoL outcomes.

Background: Data on the association between DVHs and health-related quality of life (HRQoL) in prostate cancer (PCa) patients are limited.

Materials And Methods: Five-year follow-up study of 154 patients with organ-confined (stage T1/T2) PCa treated with EBRT between January 2003 and November 2005. HRQoL was evaluated with the Expanded Prostate Cancer Index (EPIC). DVH for OARs (penile bulb, rectum and bladder) were created for all patients for whom data were available (119/154; 77%). The functional data analysis (FDA) statistical method was used. HRQoL data was collected prospectively and data analysis was performed retrospectively.

Results: Worsening of urinary incontinence and obstructive symptoms correlated with higher DVH dose distributions at 24 months. Increased rectal bleeding at months 24 and 60 correlated with higher DVH dose distributions in the 40-70 Gy range. Patients with deterioration in rectal incontinence presented a higher DVH distribution range than patients without rectal incontinence. Penile bulb DVH values and erectile dysfunction were not significantly associated.

Conclusions: DVH parameters and post-radiotherapy HRQoL appear to be closely correlated, underscoring the importance of assessing DVH values prior to initiating EBRT to determine the risk of developing HRQoL related adverse effects. Advanced treatment modalities may be appropriate in high risk cases to minimize treatment-related toxicity and to improve treatment outcomes and HRQoL. Future studies are needed to better elucidate the association between pre-treatment DVH parameters in organs at risk and subsequent HRQoL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.rpor.2018.07.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6097465PMC
August 2018

Adjuvant postoperative high-dose radiotherapy for atypical and malignant meningioma: A phase-II parallel non-randomized and observation study (EORTC 22042-26042).

Radiother Oncol 2018 08 28;128(2):260-265. Epub 2018 Jun 28.

EORTC Headquarters, Brussels, Belgium.

Purpose: The therapeutic strategy for non-benign meningiomas is controversial. The objective of this study was to prospectively investigate the impact of high dose radiation therapy (RT) on the progression-free survival (PFS) rate at 3 years in WHO grade II and III meningioma patients.

Materials And Methods: In this multi-cohorts non-randomized phase II and observational study, non-benign meningioma patients were treated according to their WHO grade and Simpson's grade. Patients with atypical meningioma (WHO grade II) and Simpson's grade 1-3 [Arm 1] entered the non-randomized phase II study designed to show a 3-year PFS > 70% (primary endpoint). All other patients entered the 3 observational cohorts: WHO grade II Simpson grade 4-5 [Arm 2] and Grade III Simpson grade 1-3 or 4-5 [Arm 3&4] in which few patients were expected.

Results: Between 02/2008 and 06/2013, 78 patients were enrolled into the study. This report focuses on the 56 (median age, 54 years) eligible patients with WHO grade II Simpson's grade 1-3 meningioma who received RT (60 Gy). At a median follow up of 5.1 years, the estimated 3-year PFS is 88.7%, hence significantly greater than 70%. Eight (14.3%) treatment failures were observed. The 3-year overall survival was 98.2%. The rate of late signs and symptoms grade 3 or more was 14.3%.

Conclusions: These data show that 3-year PFS for WHO grade II meningioma patients undergoing a complete resection (Simpson I-III) is superior to 70% when treated with high-dose (60 Gy) RT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.radonc.2018.06.018DOI Listing
August 2018

Treatment outcome and prognostic factors for adult patients with medulloblastoma: The Rare Cancer Network (RCN) experience.

Radiother Oncol 2018 Apr 17;127(1):96-102. Epub 2018 Jan 17.

Department of Radiation Oncology, Mayo Clinic Hospital, Phoenix, AZ, United States.

Background And Purpose: The optimal treatment for adults with newly diagnosed medulloblastoma (MB) has not been defined. We report a large series of cases from the Rare Cancer Network.

Material And Methods: Thirteen institutions enrolled 206 MB patients who underwent postoperative radiotherapy (RT) between 1976 and 2014. Log-rank univariate and Cox-modeled multivariate analyses were used to analyze data collected.

Results: Median patient age was 29 years; follow-up was 31 months. All patients had the tumor resected; surgery was complete in 140 (68%) patients. Postoperative RT was given in 202 (98%) patients, and 94% received craniospinal irradiation (CSI) and, usually, a posterior fossa boost. Ninety-eight (48%) patients had chemotherapy, mostly cisplatin and vincristine-based. The 10-year local control, overall survival, and disease-free survival rates were 46%, 51%, and 38%, respectively. In multivariate analyses, Karnofsky Performance Status (KPS) ≥80 and CSI were significant for disease-free and overall survival (P ≤ .04 for all); receiving chemotherapy and KPS ≥80 correlated with better local-control rates.

Conclusions: Patients with high KPS who received CSI had better rates of disease-free and overall survival. Chemotherapy was associated with better local control. These results may serve as a benchmark for future studies designed to improve outcomes for adults with medulloblastoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.radonc.2017.12.028DOI Listing
April 2018

GESIDA/PETHEMA recommendations on the diagnosis and treatment of lymphomas in patients infected by the human immunodeficiency virus.

Med Clin (Barc) 2018 07 19;151(1):39.e1-39.e17. Epub 2018 Jan 19.

Institut Català d'Oncologia, Hospital Universitari Germans Trias i Pujol, Institut de Recerca Josep Carreras, Universitat Autónoma de Barcelona, Badalona, Barcelona, España.

The incidence of non-Hodgkin's lymphoma and Hodgkin's lymphoma is higher in patients with HIV infection than in the general population. Following the introduction of combination antiretroviral therapy (cART), the prognostic significance of HIV-related variables has decreased, and lymphoma-related factors have become more pronounced. Currently, treatments for lymphomas in HIV-infected patients do not differ from those used in the general population. However, differentiating characteristics of seropositive patients, such as the need for cART and specific prophylaxis and treatment of certain opportunistic infections, should be considered. This document updates recommendations on the diagnosis and treatment of lymphomas in HIV infected patients published by GESIDA/PETHEMA in 2008.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.medcli.2017.11.037DOI Listing
July 2018

Outcome and prognostic factors in 110 consecutive patients with primary uterine leiomyosarcoma: A Rare Cancer Network study.

Chin J Cancer Res 2017 Dec;29(6):521-532

Centre Hospitalier Universitaire Vaudois (CHUV), 1011 Lausanne, Switzerland.

Objective: Primary uterine leiomyosarcomas (ULMS) are rare, and the optimal treatment is controversial. We aimed to assess the outcome and prognostic factors in a multicenter population of women treated for primary ULMS.

Methods: We retrospectively collected data of 110 women treated in 19 institutions of the Rare Cancer Network (RCN). Inclusion criteria consisted of a pathology report confirming the diagnosis of ULMS, aged 18-80 years, complete International Federation of Gynecology and Obstetrics (FIGO) stage information, complete information on treatment, and a minimum follow-up of 6 months. Local control (LC) and locoregional control (LRC), overall survival (OS) and disease-free survival (DFS) rates were computed using the Kaplan-Meier method. Univariate analysis was implemented using the log rank test, and multivariate analysis using the Cox model.

Results: All patients underwent surgery. Seventy-five patients (68%) received adjuvant radiotherapy (RT), including brachytherapy in 18 (16%). Seventeen patients (15%) received adjuvant chemotherapy. Median follow-up was 58 (range, 6-240) months. Five-year OS and DFS rates were 50% and 34%, and LC and LRC rates were 88% and 72%, respectively. On multivariate analysis, independent favorable prognostic factors were younger age, FIGO stage I, small tumor size, previous uterine disease, and no vascular invasion for OS and DFS. FIGO stage was the only favorable factor influencing LRC. Adjuvant local or systemic treatments did not improve the outcomes. Eight patients treated with RT presented a grade 3 acute toxicity, and only one patient with grade 3 late toxicity.

Conclusions: In this large population of primary ULMS patients, we found good results in terms of LC and LRC. Nevertheless, OS remains poor, mainly due to the occurrence of distant metastases. An early diagnosis seemed to improve the prognosis of the patients. Adjuvant local or systemic treatments, or more aggressive surgical procedures such as the Wertheim procedure, did not seem to impact the outcome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21147/j.issn.1000-9604.2017.06.06DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5775016PMC
December 2017

Pseudoprogression as an adverse event of glioblastoma therapy.

Cancer Med 2017 Dec 3;6(12):2858-2866. Epub 2017 Nov 3.

Pathology, Hospital del Mar, Barcelona, Spain.

We explored predictive factors of pseudoprogression (PsP) and its impact on prognosis in a retrospective series of uniformly treated glioblastoma patients. Patients were classified as having PsP, early progression (eP) or neither (nP). We examined potential associations with clinical, molecular, and basal imaging characteristics and compared overall survival (OS), progression-free survival (PFS), post-progression survival (PPS) as well as the relationship between PFS and PPS in the three groups. Of the 256 patients studied, 56 (21.9%) were classified as PsP, 70 (27.3%) as eP, and 130 (50.8%) as nP. Only MGMT methylation status was associated to PsP. MGMT methylated patients had a 3.5-fold greater possibility of having PsP than eP (OR: 3.48; 95% CI: 1.606-7.564; P = 0.002). OS was longer for PsP than eP patients (18.9 vs. 12.3 months; P = 0.0001) but was similar for PsP and nP patients (P = 0.91). OS was shorter-though not significantly so-for PsP than nP patients (OS: 19.5 vs. 27.9 months; P = 0.63) in methylated patients. PPS was similar for patients having PsP, eP or nP (PPS: 7.2 vs. 5.4 vs. 6.7; P = 0.43). Neurological deterioration occurred in 64.3% of cases at the time they were classified as PsP and in 72.8% of cases of eP (P = 0.14). PsP confounds the evaluation of disease and does not confer a survival advantage in glioblastoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cam4.1242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5727237PMC
December 2017

IDH mutation status trumps the Pignatti risk score as a prognostic marker in low-grade gliomas.

J Neurooncol 2017 Nov 7;135(2):273-284. Epub 2017 Sep 7.

Medical Oncology Service, Catalan Institute of Oncology (ICO), Hospital Germans Trias i Pujol, Ctra Canyet s/n, 08916, Badalona, Barcelona, Spain.

Management of low-grade gliomas (LGG) is based on clinical and radiologic features, including the Pignatti prognostic scoring system, which classifies patients as low- or high-risk. To determine whether molecular data can offer advantages over these features, we have examined the prognostic impact of several molecular alterations in LGG. In a cohort of 58 patients with LGG, we have retrospectively analyzed clinical and molecular characteristics, including the Pignatti criteria, IDH mutations, TP53 mutations, the 1p/19q deletion, and MGMT methylation, and correlated our findings with progression-free survival (PFS) and overall survival (OS). Mean age of patients was 45 years; 71% were classified as low-risk by the Pignatti system. IDH mutations were detected in 62%, p53 mutations in 17%, the 1p/19q codeletion in 46%, and MGMT methylation in 40% of patients. Survival analyses were performed in the 49 patients without contrast enhancement. In the univariate analysis, IDH mutations, the 1p/19q codeletion, and the combination of IDH mutations with the 1p/19q codeletion were associated with both longer PFS (P = 0.006, P = 0.037, and P = 0.003, respectively) and longer OS (P < 0.001, P = 0.02, and P < 0.001, respectively). The multivariate analysis identified absence of IDH mutations as a factor for greater risk of progression [hazard ratio (HR) = 3.1; P = 0.007]and death (HR = 6.4; P < 0.001). We suggest that IDH mutations may be more effective than the Pignatti score in discriminating low- and high-risk patients with LGG.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11060-017-2570-1DOI Listing
November 2017

Second re-irradiation for DIPG progression, re-considering "old strategies" with new approaches.

Childs Nerv Syst 2017 May 1;33(5):849-852. Epub 2017 Mar 1.

Neuro-Oncology Department, Division of Pediatric Hematology/Oncology, The Hospital for Sick Children, Toronto, Canada.

Diffuse intrinsic pontine glioma (DIPG) is an aggressive infiltrative glioma for which no curative therapy is available. Radiation therapy (RT) is the only potentially effective intervention in delaying tumor progression, but only transiently. At progression, re-irradiation is gaining popularity as an effective palliative therapy. However, at second progression, exclusive symptomatic treatment is usually offered. Here we report two patients with DIPG at second progression who were treated with a second re-irradiation course with good response. Importantly, treatment was well tolerated with no irradiation associated acute toxicity identified.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00381-017-3352-yDOI Listing
May 2017

Localized prostate cancer treated with external beam radiation therapy: Long-term outcomes at a European comprehensive cancer centre.

Rep Pract Oncol Radiother 2016 May-Jun;21(3):181-7. Epub 2016 Feb 20.

Department of Radiation Oncology, Catalan Institute of Oncology, Universidad de Barcelona, l'Hospitalet de Llobregat, Barcelona, Spain.

Aims And Background: To present survival and toxicity outcomes in patients with clinically localized, non-metastatic prostate cancer (PCa) treated with external beam radiotherapy (EBRT) combined with androgen deprivation therapy (ADT).

Materials And Methods: Retrospective study of 849 PCa patients (pts) treated from 1996 to 2005. Until August 2000, all patients (281) were treated with conventional dose EBRT (<76 Gy); subsequent pts received ≥76 Gy (565 pts). Median age was 70 years (range, 39-82). Most pts were intermediate (353; 42.8%) or high-risk (344; 41.7%). Mean PSA was 10.1 ng/ml. Median dose to the prostate was 75 Gy. Complete ADT was administered to 525 pts (61.8%).

Results: Median follow-up was 109.6 months (range, 68.3-193.4). Overall survival (OS) was 92.5% and 81.1% at 5 and 10 years; by risk group (low, intermediate, high), 5- and 10-year OS rates were 94.3% and 85.9%, 92.3% and 79.2%, and 91.9% and 80.2% (p = 0.728). Five- and 10-year BRFS was 94.1% and 80.6% (low risk), 86.4% and 70.9% (intermediate), and 85.2% and 71.4% (high) (p = 0.0666). Toxicity included rectitis: grade 1 (G1) (277 pts; 32.6%), G2 (108; 12.7%), and G3 (20; 2.6%) and urethritis: G1 (294; 34.6%); G2 (223; 26.2%), and G3 (11; 1.3%). By dose rate (<76 Gy vs. ≥76 Gy), 5 and 10-year BRFS rates were 83.1% and 68.3% vs. 88.4% and 74.8% (p = 0.038).

Conclusions: Our results are comparable to other published series in terms of disease control and toxicity. These findings confirm the need for dose escalation to achieve better biochemical control and the benefits of ADT in high-risk PCa patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.rpor.2015.12.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5002031PMC
September 2016

Phase II Study of Radiotherapy and Temsirolimus versus Radiochemotherapy with Temozolomide in Patients with Newly Diagnosed Glioblastoma without MGMT Promoter Hypermethylation (EORTC 26082).

Clin Cancer Res 2016 Oct 3;22(19):4797-4806. Epub 2016 May 3.

Neuroscience Research Center, University Hospital Lausanne (CHUV), Lausanne, Switzerland. Department of Neurosurgery, CHUV, Lausanne, Switzerland.

Purpose: EORTC 26082 assessed the activity of temsirolimus in patients with newly diagnosed glioblastoma harboring an unmethylated O6 methylguanine-DNA-methyltransferase (MGMT) promoter.

Experimental Design: Patients (n = 257) fulfilling eligibility criteria underwent central MGMT testing. Patients with MGMT unmethylated glioblastoma (n = 111) were randomized 1:1 between standard chemo-radiotherapy with temozolomide or radiotherapy plus weekly temsirolimus (25 mg). Primary endpoint was overall survival at 12 months (OS12). A positive signal was considered >38 patients alive at 12 months in the per protocol population. A noncomparative reference arm of 54 patients evaluated the assumptions on OS12 in a standard-treated cohort of patients. Prespecified post hoc analyses of markers reflecting target activation were performed.

Results: Both therapies were administered per protocol with a median of 13 cycles of maintenance temsirolimus. Median age was 55 and 58 years in the temsirolimus and standard arms, the WHO performance status 0 or 1 for most patients (95.5%). In the per protocol population, 38 of 54 patients treated with temsirolimus reached OS12. The actuarial 1-year survival was 72.2% [95% confidence interval (CI), 58.2-82.2] in the temozolomide arm and 69.6% (95% CI, 55.8-79.9) in the temsirolimus arm [hazard ratio (HR) 1.16; 95% CI, 0.77-1.76; P = 0.47]. In multivariable prognostic analyses of clinical and molecular factors, phosphorylation of mTORSer2448 in tumor tissue (HR 0.13; 95% CI, 0.04-0.47; P = 0.002), detected in 37.6%, was associated with benefit from temsirolimus.

Conclusions: Temsirolimus was not superior to temozolomide in patients with an unmethylated MGMT promoter. Phosphorylation of mTORSer2448 in the pretreatment tumor tissue may define a subgroup benefitting from mTOR inhibition. Clin Cancer Res; 22(19); 4797-806. ©2016 AACR.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1078-0432.CCR-15-3153DOI Listing
October 2016

Short Androgen Suppression and Radiation Dose Escalation for Intermediate- and High-Risk Localized Prostate Cancer: Results of EORTC Trial 22991.

J Clin Oncol 2016 05 14;34(15):1748-56. Epub 2016 Mar 14.

Michel Bolla, Centre Hospitalier Universitaire de Grenoble, Grenoble; Philippe Maingon, Georges-Francois-Leclerc Centre, Dijon; Christian Carrie, Leon Bérard Center, Lyon; Jean-François Bosset, University Hospital of Besancon-Jean Minjoz Hospital, Besancon, France; Salvador Villa, University Hospital Germans Trias I Pujol, Barcelona, Spain; Petros Kitsios, Bank of Cyprus Oncology Centre, Nicosia, Cyprus; Philip M.P. Poortmans, Radboud University Medical Center Nijmegen, Nijmegen; Elzbieta M. van der Steen-Banasik, Arnhem Radiotherapy Institute, Arnhem; Bradley Pieters, University of Amsterdam, Amsterdam; Annerie Slot, Radiotherapeutisch Instituut Friesland, Leeuwarden; Alphonsus C.M. van den Bergh, University of Groningen, Groningen, the Netherlands; Santhanam Sundar, Nottingham University Hospitals National Health Service Trust-City Hospital, Nottingham; Amit Bahl, University Hospitals Bristol National Health Service Foundation Trust-Bristol Haematology and Oncology Centre, Bristol Avon; Christopher Scrase, Ipswich Hospital National Health Service Trust, Ipswich, United Kingdom; John Armstrong, St Luke's Hospital, Dublin, Ireland; Fernanda G. Herrera, University Hospital of Lausanne, Lausanne, Switzerland; Rahamim Ben-Yosef, Rambam Health Care Campus, Haïfa, Israel; Dirk Boehmer, Charite-Universitaetsmedizin Berlin-Campus Mitte, Berlin, Germany; Laurette Renard, Cliniques Universitaires Saint Luc; Emad Shash, Corneel Coens, and Laurence Collette, European Organisation for Research and Treatment of Cancer, Brussels, Belgium; and Emad Shash, Cairo University, Cairo, Egypt.

Purpose: Up to 30% of patients who undergo radiation for intermediate- or high-risk localized prostate cancer relapse biochemically within 5 years. We assessed if biochemical disease-free survival (DFS) is improved by adding 6 months of androgen suppression (AS; two injections of every-3-months depot of luteinizing hormone-releasing hormone agonist) to primary radiotherapy (RT) for intermediate- or high-risk localized prostate cancer.

Patients And Methods: A total of 819 patients staged: (1) cT1b-c, with prostate-specific antigen (PSA) ≥ 10 ng/mL or Gleason ≥ 7, or (2) cT2a (International Union Against Cancer TNM 1997), with no involvement of pelvic lymph nodes and no clinical evidence of metastatic spread, with PSA ≤ 50 ng/mL, were centrally randomized 1:1 to either RT or RT plus AS started on day 1 of RT. Centers opted for one dose (70, 74, or 78 Gy). Biochemical DFS, the primary end point, was defined from entry until PSA relapse (Phoenix criteria) and clinical relapse by imaging or death of any cause. The trial had 80% power to detect hazard ratio (HR), 0.714 by intent-to-treat analysis stratified by dose of RT at the two-sided α = 5%.

Results: The median patient age was 70 years. Among patients, 74.8% were intermediate risk and 24.8% were high risk. In the RT arm, 407 of 409 patients received RT; in the RT plus AS arm, 403 patients received RT plus AS and three patients received RT only. At 7.2 years median follow-up, RT plus AS significantly improved biochemical DFS (HR, 0.52; 95% CI, 0.41 to 0.66; P < .001, with 319 events), as well as clinical progression-free survival (205 events, HR, 0.63; 95% CI, 0.48 to 0.84; P = .001). In exploratory analysis, no statistically significant interaction between treatment effect and dose of RT could be evidenced (heterogeneity P = .79 and P = .66, for biochemical DFS and progression-free survival, respectively). Overall survival data are not mature yet.

Conclusion: Six months of concomitant and adjuvant AS improves biochemical and clinical DFS of intermediate- and high-risk cT1b-c to cT2a (with no involvement of pelvic lymph nodes and no clinical evidence of metastatic spread) prostatic carcinoma, treated by radiation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1200/JCO.2015.64.8055DOI Listing
May 2016

Bevacizumab and temozolomide versus temozolomide alone as neoadjuvant treatment in unresected glioblastoma: the GENOM 009 randomized phase II trial.

J Neurooncol 2016 May 3;127(3):569-79. Epub 2016 Feb 3.

Radiation Oncology Service, Institut Català d'Oncologia, Hospital Universitari Germans Trias i Pujol, Badalona, Spain.

We sought to determine the impact of bevacizumab on reduction of tumor size prior to chemoradiotherapy in unresected glioblastoma patients. Patients were randomized 1:1 to receive temozolomide (TMZ arm) or temozolomide plus bevacizumab (TMZ + BEV arm). In both arms, neoadjuvant treatment was temozolomide (85 mg/m(2), days 1-21, two 28-day cycles), concurrent radiation plus temozolomide, and six cycles of adjuvant temozolomide. In the TMZ + BEV arm, bevacizumab (10 mg/kg) was added on days 1 and 15 of each neoadjuvant cycle and on days 1, 15 and 30 of concurrent treatment. The primary endpoint was investigator-assessed response to neoadjuvant treatment. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and the impact on outcome of MGMT methylation in tumor and serum. One hundred and two patients were included; 43 in the TMZ arm and 44 in the TMZ + BEV arm were evaluable for response. Results favored the TMZ + BEV arm in terms of objective response (3 [6.7 %] vs. 11 [22.9 %]; odds ratio 4.2; P = 0.04). PFS and OS were longer in the TMZ + BEV arm, though the difference did not reach statistical significance. MGMT methylation in tumor, but not in serum, was associated with outcome. More patients experienced toxicities in the TMZ + BEV than in the TMZ arm (P = 0.06). The combination of bevacizumab plus temozolomide is more active than temozolomide alone and may well confer benefit in terms of tumor shrinkage in unresected patients albeit at the expense of greater toxicity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11060-016-2065-5DOI Listing
May 2016

Small Cell Carcinoma of the Urinary Bladder: A Retrospective, Multicenter Rare Cancer Network Study of 107 Patients.

Int J Radiat Oncol Biol Phys 2015 Jul 25;92(4):904-10. Epub 2015 Mar 25.

Department of Radiation Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.

Purpose: Small cell carcinomas of the bladder (SCCB) account for fewer than 1% of all urinary bladder tumors. There is no consensus regarding the optimal treatment for SCCB.

Methods And Materials: Fifteen academic Rare Cancer Network medical centers contributed SCCB cases. The eligibility criteria were as follows: pure or mixed SCC; local, locoregional, and metastatic stages; and age ≥18 years. The overall survival (OS) and disease-free survival (DFS) were calculated from the date of diagnosis according to the Kaplan-Meier method. The log-rank and Wilcoxon tests were used to analyze survival as functions of clinical and therapeutic factors.

Results: The study included 107 patients (mean [±standard deviation, SD] age, 69.6 [±10.6] years; mean follow-up time, 4.4 years) with primary bladder SCC, with 66% of these patients having pure SCC. Seventy-two percent and 12% of the patients presented with T2-4N0M0 and T2-4N1-3M0 stages, respectively, and 16% presented with synchronous metastases. The most frequent curative treatments were radical surgery and chemotherapy, sequential chemotherapy and radiation therapy, and radical surgery alone. The median (interquartile range, IQR) OS and DFS times were 12.9 months (IQR, 7-32 months) and 9 months (IQR, 5-23 months), respectively. The metastatic, T2-4N0M0, and T2-4N1-3M0 groups differed significantly (P=.001) in terms of median OS and DFS. In a multivariate analysis, impaired creatinine clearance (OS and DFS), clinical stage (OS and DFS), a Karnofsky performance status <80 (OS), and pure SCC histology (OS) were independent and significant adverse prognostic factors. In the patients with nonmetastatic disease, the type of treatment (ie radical surgery with or without adjuvant chemotherapy vs conservative treatment) did not significantly influence OS or DFS (P=.7).

Conclusions: The prognosis for SCCB remains poor. The finding that radical cystectomy did not influence DFS or OS in the patients with nonmetastatic disease suggests that conservative treatment is appropriate in this situation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijrobp.2015.03.019DOI Listing
July 2015

High-dose radiotherapy with short-term or long-term androgen deprivation in localised prostate cancer (DART01/05 GICOR): a randomised, controlled, phase 3 trial.

Lancet Oncol 2015 Mar 19;16(3):320-7. Epub 2015 Feb 19.

Hospital General Universitario Gregorio Marañón, Madrid, Spain.

Background: The optimum duration of androgen deprivation combined with high-dose radiotherapy in prostate cancer remains undefined. We aimed to determine whether long-term androgen deprivation was superior to short-term androgen deprivation when combined with high-dose radiotherapy.

Methods: In this open-label, multicentre, phase 3 randomised controlled trial, patients were recruited from ten university hospitals throughout Spain. Eligible patients had clinical stage T1c-T3b N0M0 prostate adenocarcinoma with intermediate-risk and high-risk factors according to 2005 National Comprehensive Cancer Network criteria. Patients were randomly assigned (1:1) using a computer-generated randomisation schedule to receive either 4 months of androgen deprivation combined with three-dimensional conformal radiotherapy at a minimum dose of 76 Gy (range 76-82 Gy; short-term androgen deprivation group) or the same treatment followed by 24 months of adjuvant androgen deprivation (long-term androgen deprivation group), stratified by prostate cancer risk group (intermediate risk vs high risk) and participating centre. Patients assigned to the short-term androgen deprivation group received 4 months of neoadjuvant and concomitant androgen deprivation with subcutaneous goserelin (2 months before and 2 months combined with high-dose radiotherapy). Anti-androgen therapy (flutamide 750 mg per day or bicalutamide 50 mg per day) was added during the first 2 months of treatment. Patients assigned to long-term suppression continued with the same luteinising hormone-releasing hormone analogue every 3 months for another 24 months. The primary endpoint was biochemical disease-free survival. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT02175212.

Findings: Between Nov 7, 2005, and Dec 20, 2010, 178 patients were randomly assigned to receive short-term androgen deprivation and 177 to receive long-term androgen deprivation. After a median follow-up of 63 months (IQR 50-82), 5-year biochemical disease-free survival was significantly better among patients receiving long-term androgen deprivation than among those receiving short-term treatment (90% [95% CI 87-92] vs 81% [78-85]; hazard ratio [HR] 1·88 [95% CI 1·12-3·15]; p=0·01). 5-year overall survival (95% [95% CI 93-97] vs 86% [83-89]; HR 2·48 [95% CI 1·31-4·68]; p=0·009) and 5-year metastasis-free survival (94% [95% CI 92-96] vs 83% [80-86]; HR 2·31 [95% CI 1·23-3·85]; p=0·01) were also significantly better in the long-term androgen deprivation group than in the short-term androgen deprivation group. The effect of long-term androgen deprivation on biochemical disease-free survival, metastasis-free survival, and overall survival was more evident in patients with high-risk disease than in those with low-risk disease. Grade 3 late rectal toxicity was noted in three (2%) of 177 patients in the long-term androgen deprivation group and two (1%) of 178 in the short-term androgen deprivation group; grade 3-4 late urinary toxicity was noted in five (3%) patients in each group. No deaths related to treatment were reported.

Interpretation: Compared with short-term androgen deprivation, 2 years of adjuvant androgen deprivation combined with high-dose radiotherapy improved biochemical control and overall survival in patients with prostate cancer, particularly those with high-risk disease, with no increase in late radiation toxicity. Longer follow-up is needed to determine whether men with intermediate-risk disease benefit from more than 4 months of androgen deprivation.

Funding: Spanish National Health Investigation Fund, AstraZeneca.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S1470-2045(15)70045-8DOI Listing
March 2015

Long-term outcome of patients with spinal myxopapillary ependymoma: treatment results from the MD Anderson Cancer Center and institutions from the Rare Cancer Network.

Neuro Oncol 2015 Apr 9;17(4):588-95. Epub 2014 Oct 9.

Center of Proton Therapy, Paul Scherrer Institute, Villigen/Würenlingen, Switzerland (D.C.W.); Department of Radiation Oncology, MD Anderson Cancer Center, Houston, Texas (Y.W., J.L.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (R.M.); Department of Radiation Oncology, Catalan Institute of Oncology, Badalona, Spain (S.V.); Department of Oncology and Radiotherapy, Medical University of Gdansk, Gdansk, Poland (R.Z.); Department of Radiation Oncology, Inselspital, Bern, Switzerland (A.P.); Department of Radiation Oncology, Dr Bernard Verbeeten Instituut, Tilburg, the Netherlands (P.P.); Department of Radiation Oncology, Ege University Medical School, Izmir, Turkey (Y.A.); Department of Radiation Oncology, Faculty of Medicine, Hacettepe University, Ankara, Turkey (G.O.); Department of Robert-Janker-Klinik in Germany, Bonn, Germany (B.B.); Department of Clinical Epidemiology Unit, Department of Community Medicine, Geneva University Hospital, Geneva, Switzerland (G.H.); Department of Medicine I & Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria (M.P.).

Background: Spinal myxopapillary ependymomas (MPEs) are slowly growing ependymal gliomas with preferential manifestation in young adults. The aim of this study was to assess the outcome of patients with MPE treated with surgery, radiotherapy (RT), and/or chemotherapy.

Methods: The medical records of 183 MPE patients (male: 59%) treated at the MD Anderson Cancer Center and 11 institutions from the Rare Cancer Network were retrospectively reviewed. Mean patient' age at diagnosis was 35.5 ± 15.8 years. Ninety-seven (53.0%) patients underwent surgery without RT, and 86 (47.0%) were treated with surgery and/or RT. Median RT dose was 50.4 Gy. Median follow-up was 83.9 months.

Results: Fifteen (8.2%) patients died, 7 of unrelated cause. The estimated 10-year overall survival was 92.4% (95% CI: 87.7-97.1). Treatment failure was observed in 58 (31.7%) patients. Local failure, distant spinal relapse, and brain failure were observed in 49 (26.8%), 17 (9.3%), and 11 (6.0%) patients, respectively. The estimated 10-year progression-free survival was 61.2% (95% CI: 52.8-69.6). Age (<36 vs ≥36 y), treatment modality (surgery alone vs surgery and RT), and extent of surgery were prognostic factors for local control and progression-free survival on univariate and multivariate analysis.

Conclusions: In this series, treatment failure of MPE occurred in approximately one third of patients. The observed recurrence pattern of primary spinal MPE was mainly local, but a substantial number of patients failed nonlocally. Younger patients and those not treated initially with adjuvant RT or not undergoing gross total resection were significantly more likely to present with tumor recurrence/progression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/neuonc/nou293DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4483075PMC
April 2015

History of the rare cancer network and past research.

Rare Tumors 2014 Jul 6;6(3):5462. Epub 2014 Aug 6.

Department of Radiation Oncology, Mayo Clinic , Rochester, MN, USA.

Approximately, twenty years ago, the Rare Cancer Network (RCN) was formed in Lausanne, Switzerland, to support the study of rare malignancies. The RCN has grown over the years and now includes 130 investigators from twenty-four nations on six continents. The network held its first international symposium in Nice, France, on March 21-22, 2014. The proceedings of that meeting are presented in two companion papers. This manuscript reviews the history of the growth of the RCN and contains the abstracts of fourteen oral presentations made at the meeting of prior RCN studies. From 1993 to 2014, 74 RCN studies have been initiated, of which 54 were completed, 10 are in progress or under analysis, and 9 were stopped due to poor accrual. Forty-four peer reviewed publications have been written on behalf of the RCN.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4081/rt.2014.5462DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4178278PMC
July 2014

Neoadjuvant cisplatin plus temozolomide versus standard treatment in patients with unresectable glioblastoma or anaplastic astrocytoma: a differential effect of MGMT methylation.

J Neurooncol 2014 Mar 7;117(1):77-84. Epub 2014 Jan 7.

Medical Oncology, Catalan Institute of Oncology (ICO), University Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain.

Patients with unresectable glioblastoma or anaplastic astrocytoma have a dismal prognosis. The role of neoadjuvant chemotherapy prior to irradiation in these patients has been studied primarily in non-randomized studies. We have compared the effect of neoadjuvant chemotherapy plus radiotherapy versus concomitant radiotherapy plus temozolomide in a retrospective analysis of two consecutive series of patients in whom surgery consisted of biopsy only. From 2003 to 2005, 23 patients received two cycles of temozolomide plus cisplatin followed by radiotherapy (Cohort 1), and from 2006 to 2010, 23 additional patients received concomitant radiotherapy and temozolomide followed by adjuvant temozolomide (Cohort 2). In Cohort 1, 91.3 % of patients received all planned chemotherapy cycles. Progression-free and overall survival were 3.3 and 8.5 months, respectively. In Cohort 2, progression-free and overall survival were 5.1 and 11.2 months, respectively. No differences between the two groups were observed in rate of completion of radiotherapy, progression-free or overall survival. MGMT methylation was assessed in 91.3 % of patients. In Cohort 1, patients without MGMT methylation showed a trend towards shorter progression-free survival (P = 0.09), while in Cohort 2, patients without MGMT methylation had longer progression-free survival (P = 0.04). In the overall patient population, neoadjuvant temozolomide plus cisplatin had neither a positive nor negative influence on outcome. However, our findings indicate that patients with methylated MGMT may derive greater benefit from neoadjuvant temozolomide than those with unmethylated MGMT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11060-013-1352-7DOI Listing
March 2014

Radiation and concomitant chemotherapy for patients with glioblastoma multiforme.

Chin J Cancer 2014 Jan 11;33(1):25-31. Epub 2013 Dec 11.

Radiation Oncology, Catalan Institute of Oncology, HU Germans Trias, Badalona 08916, Catalonia, Spain.

Postoperative external beam radiotherapy was considered the standard adjuvant treatment for patients with glioblastoma multiforme until the advent of using the drug temozolomide (TMZ) in addition to radiotherapy. High-dose volume should be focal, minimizing whole brain irradiation. Modern imaging, using several magnetic resonance sequences, has improved the planning target volume definition. The total dose delivered should be in the range of 60 Gy in fraction sizes of 1.8-2.0 Gy. Currently, TMZ concomitant and adjuvant to radiotherapy has become the standard of care for glioblastoma multiforme patients. Radiotherapy dose-intensification and radiosensitizer approaches have not improved the outcome. In spite of the lack of high quality evidence, stereotactic radiotherapy can be considered for a selected group of patients. For elderly patients, data suggest that the same survival benefit can be achieved with similar morbidity using a shorter course of radiotherapy (hypofractionation). Elderly patients with tumors that exhibit methylation of the O-6-methylguanine-DNA methyltransferase promoter can benefit from TMZ alone.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5732/cjc.013.10216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3905087PMC
January 2014

Quality assurance of radiotherapy in the ongoing EORTC 22042-26042 trial for atypical and malignant meningioma: results from the dummy runs and prospective individual case Reviews.

Radiat Oncol 2013 Jan 30;8:23. Epub 2013 Jan 30.

Department of Radiation Oncology, Ankara Oncology Hospital, Ankara, Turkey.

Background: The ongoing EORTC 22042-26042 trial evaluates the efficacy of high-dose radiotherapy (RT) in atypical/malignant meningioma. The results of the Dummy Run (DR) and prospective Individual Case Review (ICR) were analyzed in this Quality Assurance (QA) study.

Material/methods: Institutions were requested to submit a protocol compliant treatment plan for the DR and ICR, respectively. DR-plans (n=12) and ICR-plans (n=50) were uploaded to the Image-Guided Therapy QA Center of Advanced Technology Consortium server (http://atc.wustl.edu/) and were assessed prospectively.

Results: Major deviations were observed in 25% (n=3) of DR-plans while no minor deviations were observed. Major and minor deviations were observed in 22% (n=11) and 10% (n=5) of the ICR-plans, respectively. Eighteen% of ICRs could not be analyzed prospectively, as a result of corrupted or late data submission. CTV to PTV margins were respected in all cases. Deviations were negatively associated with the number of submitted cases per institution (p=0.0013), with a cutoff of 5 patients per institutions. No association (p=0.12) was observed between DR and ICR results, suggesting that DR's results did not predict for an improved QA process in accrued brain tumor patients.

Conclusions: A substantial number of protocol deviations were observed in this prospective QA study. The number of cases accrued per institution was a significant determinant for protocol deviation. These data suggest that successful DR is not a guarantee for protocol compliance for accrued patients. Prospective ICRs should be performed to prevent protocol deviations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1748-717X-8-23DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3564920PMC
January 2013

A European Organisation for Research and Treatment of Cancer phase III trial of adjuvant whole-brain radiotherapy versus observation in patients with one to three brain metastases from solid tumors after surgical resection or radiosurgery: quality-of-life results.

J Clin Oncol 2013 Jan 3;31(1):65-72. Epub 2012 Dec 3.

University of Torino and San Giovanni Battista Hospital, Turin, Italy.

Purpose: This phase III trial compared adjuvant whole-brain radiotherapy (WBRT) with observation after either surgery or radiosurgery of a limited number of brain metastases in patients with stable solid tumors. Here, we report the health-related quality-of-life (HRQOL) results.

Patients And Methods: HRQOL was a secondary end point in the trial. HRQOL was assessed at baseline, at 8 weeks, and then every 3 months for 3 years with the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 and Brain Cancer Module. The following six primary HRQOL scales were considered: global health status; physical, cognitive, role, and emotional functioning; and fatigue. Statistical significance required P ≤ .05, and clinical relevance required a ≥ 10-point difference.

Results: Compliance was 88.3% at baseline and dropped to 45.0% at 1 year; thus, only the first year was analyzed. Overall, patients in the observation only arm reported better HRQOL scores than did patients who received WBRT. The differences were statistically significant and clinically relevant mostly during the early follow-up period (for global health status at 9 months, physical functioning at 8 weeks, cognitive functioning at 12 months, and fatigue at 8 weeks). Exploratory analysis of all other HRQOL scales suggested worse scores for the WBRT group, but none was clinically relevant.

Conclusion: This study shows that adjuvant WBRT after surgery or radiosurgery of a limited number of brain metastases from solid tumors may negatively impact some aspects of HRQOL, even if these effects are transitory. Consequently, observation with close monitoring with magnetic resonance imaging (as done in the EORTC trial) is not detrimental for HRQOL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1200/JCO.2011.41.0639DOI Listing
January 2013

Primary pineal tumors: outcome and prognostic factors--a study from the Rare Cancer Network (RCN).

Clin Transl Oncol 2012 Nov 23;14(11):827-34. Epub 2012 Aug 23.

Radiation Oncology, Catalan Institute of Oncology, H. Universitari Germans Trías, Badalona, Barcelona, Catalonia, Spain.

Purpose: To better define outcome and prognostic factors in primary pineal tumors.

Materials And Methods: Thirty-five consecutive patients from seven academic centers of the Rare Cancer Network diagnosed between 1988 and 2006 were included. Median age was 36 years. Surgical resection consisted of biopsy in 12 cases and resection in 21 (2 cases with unknown resection). All patients underwent radiotherapy and 12 patients received also chemotherapy.

Results: Histological subtypes were pineoblastoma (PNB) in 21 patients, pineocytoma (PC) in 8 patients and pineocytoma with intermediate differentiation in 6 patients. Six patients with PNB had evidence of spinal seeding. Fifteen patients relapsed (14 PNB and 1 PC) with PNB cases at higher risk (p = 0.031). Median survival time was not reached. Median disease-free survival was 82 months (CI 50 % 28-275). In univariate analysis, age younger than 36 years was an unfavorable prognostic factor (p = 0.003). Patients with metastases at diagnosis had poorer survival (p = 0.048). Late side effects related to radiotherapy were dementia, leukoencephalopathy or memory loss in seven cases, occipital ischemia in one, and grade 3 seizures in two cases. Side effects related to chemotherapy were grade 3-4 leucopenia in five cases, grade 4 thrombocytopenia in three cases, grade 2 anemia in two cases, grade 4 pancytopenia in one case, grade 4 vomiting in one case and renal failure in one case.

Conclusions: Age and dissemination at diagnosis influenced survival in our series. The prevalence of chronic toxicity suggests that new adjuvant strategies are advisable.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12094-012-0869-0DOI Listing
November 2012