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Most Cited Radiotherapy & Oncology Articles
The most cited articles published since 2011, extracted from Scopus.
Clinical outcome of protocol based image (MRI) guided adaptive brachytherapy combined with 3D conformal radiotherapy with or without chemotherapy in patients with locally advanced cervical cancerRichard Pötter | Petra Georg | Johannes C A Dimopoulos | Magdalena Grimm | Daniel Berger | Nicole Nesvacil | Dietmar Georg | Maximilian P. Schmid | Alexander Reinthaller | Alina Sturdza | Christian Kirisits
Volume 100, Issue 1, July 2011, Pages 116-123
Background: To analyse the overall clinical outcome and benefits by applying protocol based image guided adaptive brachytherapy combined with 3D conformal external beam radiotherapy (EBRT) ± chemotherapy (ChT). Methods: Treatment schedule was EBRT with 45-50.4 Gy ± concomitant cisplatin chemotherapy plus 4 × 7 Gy High Dose Rate (HDR) brachytherapy. Patients were treated in the "protocol period" (2001-2008) with the prospective application of the High Risk CTV concept (D90) and dose volume constraints for organs at risk including biological modelling. Dose volume adaptation was performed with the aim of dose escalation in large tumours (prescribed D90 > 85 Gy), often with inserting additional interstitial needles. Dose volume constraints (D 2cc) were 70-75 Gy for rectum and sigmoid and 90 Gy for bladder. Late morbidity was prospectively scored, using LENT/SOMA Score. Disease outcome and treatment related late morbidity were evaluated and compared using actuarial analysis. Findings: One hundred and fifty-six consecutive patients (median age 58 years) with cervix cancer FIGO stages IB-IVA were treated with definitive radiotherapy in curative intent. Histology was squamous cell cancer in 134 patients (86%), tumour size was >5 cm in 103 patients (66%), lymph node involvement in 75 patients (48%). Median follow-up was 42 months for all patients. Interstitial techniques were used in addition to intracavitary brachytherapy in 69/156 (44%) patients. Total prescribed mean dose (D90) was 93 ± 13 Gy, D 2cc 86 ± 17 Gy for bladder, 65 ± 9 Gy for rectum and 64 ± 9 Gy for sigmoid. Complete remission was achieved in 151/156 patients (97%). Overall local control at 3 years was 95%; 98% for tumours 2-5 cm, and 92% for tumours >5 cm (p = 0.04), 100% for IB, 96% for IIB, 86% for IIIB. Cancer specific survival at 3 years was overall 74%, 83% for tumours 2-5 cm, 70% for tumours >5 cm, 83% for IB, 84% for IIB, 52% for IIIB. Overall survival at 3 years was in total 68%, 72% for tumours 2-5 cm, 65% for tumours >5 cm, 74% for IB, 78% for IIB, 45% for IIIB. In regard to late morbidity in total 188 grade 1 + 2 and 11 grade 3 + 4 late events were observed in 143 patients. G1 + 2/G3 + 4 events for bladder were n = 32/3, for rectum n = 14/5, for bowel (including sigmoid) n = 3/0, for vagina n = 128/2, respectively. Interpretation: 3D conformal radiotherapy ± chemotherapy plus image (MRI) guided adaptive intracavitary brachytherapy including needle insertion in advanced disease results in local control rates of 95-100% at 3 years in limited/favourable (IB/IIB) and 85-90% in large/poor response (IIB/III/IV) cervix cancer patients associated with a moderate rate of treatment related morbidity. Compared to the historical Vienna series there is relative reduction in pelvic recurrence by 65-70% and reduction in major morbidity. The local control improvement seems to have impact on CSS and OS. Prospective clinical multi-centre studies are mandatory to evaluate these challenging mono-institutional findings. © 2011 Elsevier Ltd. All rights reserved.
Hypoxic modification of radiotherapy in squamous cell carcinoma of the head and neck - A systematic review and meta-analysisJens Overgaard
Volume 100, Issue 1, July 2011, Pages 22-32
Background: The importance of tumour hypoxia for the outcome of radiotherapy has been under investigation for decades. Numerous clinical trials modifying the hypoxic radioresistance in squamous cell carcinoma of the head and neck (HNSCC) have been conducted, but most have been inconclusive, partly due to a small number of patients in the individual trial. The present meta-analysis was, therefore, performed utilising the results from all clinical trials addressing the specific question of hypoxic modification in HNSCC undergoing curative intended primary radiotherapy alone. Methods: A systematic review of published and unpublished data identified 4805 patients with HNSCC treated in 32 randomized clinical trials, applying, normobaric oxygen or carbogen breathing (5 trials); hyperbaric oxygen (HBO) (9 trials); hypoxic radiosensitizers (17 trials) and HBO and radiosensitizer (1 trial). The trials were analysed with regard to the following endpoints: loco-regional control (32 trials), disease specific survival (30 trials), overall survival (29 trials), distant metastases (12 trials) and complications to radiotherapy (23 trials). Results: Overall hypoxic modification of radiotherapy in head and neck cancer did result in a significant improved therapeutic benefit. This was most dominantly observed when using the direct endpoint of loco-regional control with an odds ratio (OR) of 0.71, 95% cf.l. 0.63-0.80; p < 0.001), but this was almost mirrored in the disease specific survival (OR: 0.73, 95% cf.l. 0.64-0.82; p < 0.001), and to a lesser extent in the overall survival (OR: 0.87, 95% cf.l. 0.77-0.98; p = 0.03). The risk of distant metastases was not significantly influenced although it appears to be less in the tumours treated with hypoxic modification (OR: 0.87, 95% cf.l. 0.69-1.09; p = 0.22), whereas the radiation related late complications were not influenced by the overall use of hypoxic modifications (OR: 1.00, 95% cf.l. 0.82-1.23; p = 0.96). The improvement in loco-regional control was found to be independent of the type of hypoxic modification. The trials have used different fractionation schedules, including large doses per fraction, which may result in relatively more hypoxia and greater benefit. However, analysis of HNSCC trials using conventional fractionation only, showed that the significant effect of hypoxic modification was maintained. Conclusion: The meta-analysis thus demonstrates that there is level 1a evidence in favour of adding hypoxic modification to radiotherapy of squamous cell carcinomas of the head and neck. © 2011 Elsevier Ltd. All rights reserved.
Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): A comprehensive analysis by tumour sitePierre Blanchard | Bertrand Baujat | Victoria Holostenco | Abderrahmane Bourredjem | Charlotte Baey | Jean Bourhis | Jean Pierre Pignon
Volume 100, Issue 1, July 2011, Pages 33-40
Introduction: The recently updated meta-analysis of chemotherapy in head and neck cancer (MACH-NC) demonstrated the benefit of the addition of chemotherapy in terms of overall survival in head and neck squamous cell carcinoma (HNSCC). The magnitude of the benefit according to tumour site is unknown as well as their potential interactions with patient or trial characteristics. Methods: Eighty seven randomized trials performed between 1965 and 2000 were included in the present analysis. Patients were divided into four categories according to tumour location: oral cavity, oropharynx, hypopharynx and larynx. Patients with other tumour location were excluded (999, 5.7%). For each tumour location and chemotherapy timing, the logrank-test, stratified by trial, was used to compare treatments. The hazard ratios of death or relapse were calculated. Interactions between patient or trial characteristics and chemotherapy effect were studied. Results: Individual patient data of 16,192 patients were analysed, with a median follow-up of 5.6 years. The benefit of the addition is consistent in all tumour locations, with hazard ratios between 0.87 and 0.88 (p-value of interaction = 0.99). Chemotherapy benefit was higher for concomitant administration for all tumour locations, but the interaction test between chemotherapy timing and treatment effect was only significant for oropharyngeal (p < 0.0001) and laryngeal tumours (p = 0.05), and not for oral cavity (p = 0.15) and hypopharyngeal tumours (p = 0.30). The 5-year absolute benefits associated with the concomitant chemotherapy are 8.9%, 8.1%, 5.4% and 4% for oral cavity, oropharynx, larynx and hypopharynx tumours, respectively. Conclusion: The benefit of the addition of chemotherapy to locoregional treatment is consistent in all tumour locations of HNSCC. The higher benefit of concomitant schedule was demonstrated only for oropharyngeal and laryngeal tumours but this may be only a consequence of a lack of power. © 2011 Elsevier Ltd. All rights reserved.
A prospective, randomized study comparing outcomes and toxicities of intensity-modulated radiotherapy vs. conventional two-dimensional radiotherapy for the treatment of nasopharyngeal carcinomaGang Peng | Tao Wang | Kun Yu Yang | Sheng Zhang | Tao Zhang | Qin Li | Jun Han | Gang Wu
Volume 104, Issue 3, September 2012, Pages 286-293
Background and Purpose: To compare clinical outcomes and toxicities of two-dimensional conventional radiation therapy (2D-CRT) and intensity modulated radiation therapy (IMRT) for the treatment of nasopharyngeal carcinoma (NPC). Materials and methods: Between July 2003 and October 2008, 616 patients with non-metastatic stage I to IVb NPC were prospectively randomized to receive 2D-CRT (n = 310; mean age, 44.8 ± 13.6 years) or IMRT (n = 306; mean age, 46.7 ± 12.5 years). Clinical outcomes and acute and late toxicities were determined and compared. Results: The 2 groups were comparable with respect to all parameters of demographics and disease characteristics (all, p > 0.05). Median follow-up was 42 months (range, 1-83 months). The 5-year actuarial local control rate was 90.5% in the IMRT group and 84.7% in the 2D-CRT group. The local control rates were 91% for stage T3 and 81.5% for stage T4 disease in the IMRT group and 80% and 62.2% in the 2D-CRT group, respectively. The 5-year actuarial nodal relapse-free survival (NRFS) rate was 92.4% in the IMRT and 92.9% in the 2D-CRT group (p > 0.05). The NRFS was 93.9% for N2 disease in the IMRT group and 91.4% in the 2D-CRT group (p = 0.02). The 5-year overall survival (OS) rate was 79.6% for the IMRT group and 67.1% for the 2D-CRT group (p = 0.001). When stratified for stage, a significant difference was only noted for stage III disease. In terms of radiation-induced toxicities, patients in IMRT group had significantly lower radiation-induced toxicities than those in 2D-CRT group. Conclusion: IMRT provides improved local-recurrence free survival, especially in late-stage NPC patients and is associated with a lower incidence of toxicities. © 2012 Elsevier Ireland Ltd. All rights reserved.
Incidence of heart disease in 35,000 women treated with radiotherapy for breast cancer in Denmark and SwedenPaul McGale | Sarah C. Darby | Per Hall | Jan Adolfsson | Nils Olof Bengtsson | Anna M. Bennet | Tommy Fornander | Bruna Gigante | Maj Britt Jensen | Richard Peto | Kazem Rahimi | Carolyn W. Taylor | Marianne Ewertz
Volume 100, Issue 2, August 2011, Pages 167-175
Purpose: To study incidence of radiation-related heart disease in a large population of breast cancer patients followed for up to 30 years. Material and methods: 72,134 women diagnosed with breast cancer in Denmark or Sweden during 1976-2006 and followed prospectively. Radiation-related risk was studied by comparing women with left-sided and right-sided tumours. Results: 34,825 women (48%) received radiotherapy. Among unirradiated women tumour laterality had little relevance to heart disease. Among irradiated women mean dose to the whole heart was 6.3 Gy for left-sided tumours and 2.7 Gy for right-sided tumours. Mortality was similar in irradiated women with left-sided and right-sided tumours, but incidence ratios, left-sided versus right-sided, were raised: acute myocardial infarction 1.22 (95% CI 1.06-1.42), angina 1.25 (1.05-1.49), pericarditis 1.61 (1.06-2.43), valvular heart disease 1.54 (1.11-2.13). Incidence ratios for all heart disease were as high for women irradiated since 1990 (1.09 [1.00-1.19]) as for women irradiated during 1976-1989 (1.08 [0.99-1.17]), and were higher for women diagnosed with ischaemic heart disease prior to breast cancer than for other women (1.58 [1.19-2.10] versus 1.08 [1.01-1.15], p for difference = 0.01). Conclusions: Breast cancer radiotherapy has, at least until recently, increased the risk of developing ischaemic heart disease, pericarditis and valvular disease. Women with ischaemic heart disease before breast cancer diagnosis may have incurred higher risks than others. © 2011 Elsevier Ireland Ltd. All rights reserved.
FAZA PET/CT hypoxia imaging in patients with squamous cell carcinoma of the head and neck treated with radiotherapy: Results from the DAHANCA 24 trialLise Sakso Mortensen | Jørgen Johansen | Jesper Kallehauge | Hanne Primdahl | Morten Busk | Pernille Lassen | Jan Alsner | Brita S. Sørensen | Kasper Toustrup | Steen Jakobsen | Jørgen Petersen | Henrik Petersen | Jørn Theil | Marianne Nordsmark | Jens Overgaard
Volume 105, Issue 1, October 2012, Pages 14-20
Purpose: Hypoxia is a cause of resistance to radiotherapy, especially in patients with head and neck squamous cell carcinoma (HNSCC). The purpose of this study was to evaluate 18F-fluoroazomycin arabinoside (FAZA) positron emission tomography (PET)/computed tomography (CT) hypoxia imaging as a prognostic factor in HNSCC patients receiving radiotherapy. Material and methods: Forty patients with HNSCC treated with radiotherapy (66-76 Gy) were included. Static FAZA PET/CT imaging 2 h post injection was conducted prior to irradiation. The hypoxic volume (HV) was delineated using a tumor-to-muscle value ≥1.4. In 13 patients, a repetitive FAZA PET/CT scan was conducted during the radiotherapy treatment. Results: A hypoxic volume could be identified in 25 (63%) of the 40 tumors. FAZA PET HV varied considerably with a range from 0.0 to 30.9 (median: 0.3) cm3. The Tmax/Mmed ranged from 1.1 to 2.9 (median: 1.5). The distribution of hypoxia among the Human Papillomavirus (HPV) positive (12/16) and negative (13/24) tumors was not significant different. In the FAZA PET/CT scans performed during radiotherapy, hypoxia could be detected in six of the 13 patients. For these six patients the location of HV remained stable in location during radiotherapy treatment, though the size of the HV decreased. In 30 patients a positive correlation was detected between maximum FAZA uptake in the primary tumor and the lymph node. During a median follow up of 19 months a significant difference in disease free survival rate with 93% for patients with non hypoxic tumors and 60% for patients with hypoxic tumors could be detected. Conclusion: This study emphasizes the role of FAZA PET/CT imaging as a suitable assay with prognostic potential for detection of hypoxia in HNSCC. © 2011 Elsevier Ireland Ltd. All rights reserved.
Randomised trial of external beam radiotherapy alone or combined with high-dose-rate brachytherapy boost for localised prostate cancerPeter J. Hoskin | Ana M. Rojas | Peter J. Bownes | Gerry J. Lowe | Peter J. Ostler | Linda Bryant
Volume 103, Issue 2, May 2012, Pages 217-222
Background: A randomised phase-III trial compared external beam radiotherapy (EBRT) alone with EBRT combined with high-dose-rate brachytherapy boost (HDR-BTb) in localised prostate adenocarcinoma. Methods: From December 1997 to August 2005, 218 patients were assigned to EBRT alone (n = 108) or EBRT followed by a temporary high-dose-rate implant (n = 110). Patients were stratified according to tumour stage, PSA, Gleason score and androgen deprivation therapy (ADT). Biochemical/clinical relapse-free survival (RFS) was the primary endpoint. Secondary endpoints were overall survival (OS), urinary and bowel toxicity. Results: RFS was significantly higher in patients treated with EBRT + HDR-BTb (log rank p = 0.04). In multivariate analysis treatment arm, risk category and ADT were significant covariates for risk of relapse. Differences in OS were not significant. Incidence of severe late urinary and bowel morbidity was similar. Conclusions: EBRT + HDR-BTb resulted in a significant improvement in RFS compared to EBRT alone with a 31% reduction in the risk of recurrence (p = 0.01) and similar incidence of severe late urinary and rectal morbidity. © 2011 Elsevier Ireland Ltd. All rights reserved.
Stereotactic body radiotherapy for localized prostate cancer: Pooled analysis from a multi-institutional consortium of prospective phase II trialsChristopher R. King | Debra Freeman | Irving Kaplan | Donald Fuller | Giampaolo Bolzicco | Sean Collins | Robert Meier | Jason Wang | Patrick Kupelian | Michael Steinberg | Alan Katz
Volume 109, Issue 2, November 2013, Pages 217-221
Purpose The effectiveness of stereotactic body radiotherapy (SBRT) for localized prostate cancer is tested. Methods and materials A total of 1100 patients with clinically localized prostate cancer were enrolled in separate prospective phase 2 clinical trials of SBRT from 8 institutions during 2003-11 and pooled for analysis. SBRT using the CyberKnife delivered a median dose of 36.25 Gy in 4-5 fractions. Patients were low-risk (58%), intermediate-risk (30%) and high-risk (11%). A short-course of androgen deprivation therapy (ADT) was given to 14%. PSA relapse defined as a rise >2 ng/ml above nadir was analyzed with the Kaplan Meier method. Results With a median follow-up of 36 months there were 49 patients with PSA failure (4.5%), 9 of whom were subsequently determined to be benign PSA bounces. The 5-year biochemical relapse free survival (bRFS) rate was 93% for all patients; 95%, 83% and 78% for GS ≤6, 7 and ≥8, respectively (p = 0.001), and 95%, 84% and 81% for low-, intermediate- and high-risk patients, respectively (p < 0.001). No differences were observed with ADT (p = 0.71) or as a function of total dose (p = 0.17). A PSA bounce of >0.2 ng/ml was noted among 16% of patients. For 135 patients possessing a minimum of 5 years follow-up, the 5-year bRFS rate for low- and intermediate-risk patients was 99% and 93%, respectively. Conclusion PSA relapse-free survival rates after SBRT compare favorably with other definitive treatments for low and intermediate risk patients. The current evidence supports consideration of SBRT among the therapeutic options for these patients. © 2013 Elsevier Ireland Ltd. All rights reserved.
Recommendations from Gynaecological (GYN) GEC-ESTRO Working Group (IV): Basic principles and parameters for MR imaging within the frame of image based adaptive cervix cancer brachytherapyJohannes C A Dimopoulos | Peter Petrow | Kari Tanderup | Primoz Petric | Daniel Berger | Christian Kirisits | Erik M. Pedersen | Erik Van Limbergen | Christine Haie-Meder | Richard Pötter
Volume 103, Issue 1, April 2012, Pages 113-122
The GYN GEC-ESTRO working group issued three parts of recommendations and highlighted the pivotal role of MRI for the successful implementation of 3D image-based cervical cancer brachytherapy (BT). The main advantage of MRI as an imaging modality is its superior soft tissue depiction quality. To exploit the full potential of MRI for the better ability of the radiation oncologist to make the appropriate choice for the BT application technique and to accurately define the target volumes and the organs at risk, certain MR imaging criteria have to be fulfilled. Technical requirements, patient preparation, as well as image acquisition protocols have to be tailored to the needs of 3D image-based BT. The present recommendation is focused on the general principles of MR imaging for 3D image-based BT. Methods and parameters have been developed and progressively validated from clinical experience from different institutions (IGR, Universities of Vienna, Leuven, Aarhus and Ljubljana) and successfully applied during expert meetings, contouring workshops, as well as within clinical and interobserver studies. It is useful to perform pelvic MRI scanning prior to radiotherapy ("Pre-RT-MRI examination") and at the time of BT ("BT MRI examination") with one MR imager. Both low and high-field imagers, as well as both open and close magnet configurations conform to the requirements of 3D image-based cervical cancer BT. Multiplanar (transversal, sagittal, coronal and oblique image orientation) T2-weighted images obtained with pelvic surface coils are considered as the golden standard for visualisation of the tumour and the critical organs. The use of complementary MRI sequences (e.g. contrast-enhanced T1-weighted or 3D isotropic MRI sequences) is optional. Patient preparation has to be adapted to the needs of BT intervention and MR imaging. It is recommended to visualise and interpret the MR images on dedicated DICOM-viewer workstations, which should also assist the contouring procedure. Choice of imaging parameters and BT equipment is made after taking into account aspects of interaction between imaging and applicator reconstruction, as well as those between imaging, geometry and dose calculation. In a prospective clinical context, to implement 3D image-based cervical cancer brachytherapy and to take advantage of its full potential, it is essential to successfully meet the MR imaging criteria described in the present recommendations of the GYN GEC-ESTRO working group. © 2012 Elsevier Ireland Ltd. All rights reserved.
Autophagy contributes to resistance of tumor cells to ionizing radiationHassan Chaachouay | Petra Ohneseit | Mahmoud Toulany | Rainer Kehlbach | Gabriele Multhoff | H. Peter Rodemann
Volume 99, Issue 3, June 2011, Pages 287-292
Background and purpose: Autophagy signaling is a novel important target to improve anticancer therapy. To study the role of autophagy on resistance of tumor cells to ionizing radiation (IR), breast cancer cell lines differing in their intrinsic radiosensitivity were used. Materials and methods: Breast cancer cell lines MDA-MB-231 and HBL-100 were examined with respect to clonogenic cell survival and induction of autophagy after radiation exposure and pharmacological interference of the autophagic process. As marker for autophagy the appearance of LC3-I and LC3-II proteins was analyzed by SDS-PAGE and Western blotting. Formation of autophagic vacuoles was monitored by immunofluorescence staining of LC3. Results: LC3-I and LC3-II formation differs markedly in radioresistant MDA-MB-231 versus radiosensitive HBL-100 cells. Western blot analyses of LC3-II/LC3-I ratio indicated marked induction of autophagy by IR in radioresistant MDA-MB-231 cells, but not in radiosensitive HBL-100 cells. Indirect immunofluorescence analysis of LC3-II positive vacuoles confirmed this differential effect. Pre-treatment with 3-methyladenine (3-MA) antagonized IR-induced autophagy. Likewise, pretreatment of radioresistant MDA-231 cells with autophagy inhibitors 3-MA or chloroquine (CQ) significantly reduced clonogenic survival of irradiated cells. Conclusion: Our data clearly indicate that radioresistant breast tumor cells show a strong post-irradiation induction of autophagy, which thus serves as a protective and pro-survival mechanism in radioresistance. © 2011 Elsevier Ireland Ltd. All rights reserved.
Exploratory prospective trial of hypoxia-specific PET imaging during radiochemotherapy in patients with locally advanced head-and-neck cancerDaniel Zips | Klaus Zöphel | Nasreddin Abolmaali | Rosalind Perrin | Andrij Abramyuk | Robert Haase | Steffen Appold | Jörg Steinbach | Jörg Kotzerke | Michael Baumann
Volume 105, Issue 1, October 2012, Pages 21-28
Purpose: To explore in a prospective trial the prognostic value of hypoxia imaging before and during radiochemotherapy in patients with locally advanced head and neck cancer. Patients and methods: Twenty-five patients with stage III/IV head and neck cancer were investigated with [18F]- fluoromisonidazole (FMISO) PET/CT at four time points during radiochemotherapy (baseline, 8-10 Gy, 18-20 Gy,50-60 Gy). FMISO PET/CT image parameters were extracted including maximum-tumour-to-background (TBRmax) and thresholded volume at different TBR ratios. CT volume and baseline FDG-PET/CT image parameters were also included. Parameters at all time points were investigated for their prognostic value with the local-progression-free-survival endpoint (LPFS). Significance was evaluated with multivariate Cox (including clinical parameters) and Log-rank tests. Results: FMISO-image parameters were found to have a strong association with the LPFS endpoint, and were strongest at the week 1 and 2 time points (p = 0.023-0.048 and 0.042-0.061 respectively on multivariate Cox). Parameters measured at baseline were only significant on univariate analysis. None of the clinical parameters, and also FDG- or CT-delineated volumes, were significantly associated with LPFS. Conclusion: This prospective, exploratory study demonstrated that FMISO-PET/CT imaging during the initial phase of treatment carries strong prognostic value. FMISO-PET/CT imaging at 1 or 2 weeks during treatment could be promising way to select patients that would benefit from hypoxia modification or dose-escalated treatment. A validation study is on-going. © 2011 Elsevier Ireland Ltd. All rights reserved.
Reduced dose radiotherapy for local control in non-Hodgkin lymphoma: A randomised phase III trialLisa Lowry | Paul Smith | Wendi Qian | Stephen Falk | Kim Benstead | Tim Illidge | David Linch | Martin Robinson | Andrew Jack | Peter Hoskin
Volume 100, Issue 1, July 2011, Pages 86-92
Purpose: This multicentre, prospective, randomised-controlled trial compared efficacy and toxicity of differing radiotherapy doses in non-Hodgkin lymphoma (NHL). Patients and methods: Patients with any histological subtype of NHL, requiring radiotherapy for local disease control, whether radical, consolidative or palliative, were included. Three hundred and sixty one sites of indolent NHL (predominantly follicular NHL and marginal zone lymphoma) were randomised to receive 40-45 Gy in 20-23 fractions or 24 Gy in 12 fractions. Six hundred and forty sites of aggressive NHL (predominantly diffuse large B cell lymphoma as part of combined-modality therapy) were randomised to receive 40-45 Gy in 20-23 fractions or 30 Gy in 15 fractions. Patients with all stages of disease, having first-line and subsequent therapies were included; first presentations of early-stage disease predominated. Results: There was no difference in overall response rate (ORR) between standard and lower-dose arms. In the indolent group, ORR was 93% and 92%, respectively, (p = 0.72); in the aggressive group, ORR was 91% in both arms (p = 0.87). With a median follow-up of 5.6 years, there was no significant difference detected in the rate of within-radiation field progression (HR = 1.09, 95%CI = 0.76-1.56, p = 0.64 in the indolent group; HR = 0.98, 95%CI = 0.68-1.4, p = 0.89 in the aggressive group). There was also no significant difference detected in the progression free or overall survival. There was a trend for reduced toxicities in the low-dose arms; only the reduction in reported erythema reached significance. Conclusion: In a large, randomised trial, there was no loss of efficacy associated with radiotherapy doses of 24 Gy in indolent NHL and 30 Gy in aggressive NHL, compared with previous standard doses of 40-45 Gy. © 2011 Elsevier Ltd. All rights reserved.
An evidence based review of proton beam therapy: The report of ASTRO's emerging technology committeeAaron M. Allen | Todd Pawlicki | Lei Dong | Eugene Fourkal | Mark Buyyounouski | Keith Cengel | John Plastaras | Mary K. Bucci | Torunn I. Yock | Luisa Bonilla | Robert Price | Eleanor E. Harris | Andre A. Konski
Volume 103, Issue 1, April 2012, Pages 8-11
Proton beam therapy (PBT) is a novel method for treating malignant disease with radiotherapy. The purpose of this work was to evaluate the state of the science of PBT and arrive at a recommendation for the use of PBT. The emerging technology committee of the American Society of Radiation Oncology (ASTRO) routinely evaluates new modalities in radiotherapy and assesses the published evidence to determine recommendations for the society as a whole. In 2007, a Proton Task Force was assembled to evaluate the state of the art of PBT. This report reflects evidence collected up to November 2009. Data was reviewed for PBT in central nervous system tumors, gastrointestinal malignancies, lung, head and neck, prostate, and pediatric tumors. Current data do not provide sufficient evidence to recommend PBT in lung cancer, head and neck cancer, GI malignancies, and pediatric non-CNS malignancies. In hepatocellular carcinoma and prostate cancer and there is evidence for the efficacy of PBT but no suggestion that it is superior to photon based approaches. In pediatric CNS malignancies PBT appears superior to photon approaches but more data is needed. In large ocular melanomas and chordomas, we believe that there is evidence for a benefit of PBT over photon approaches. PBT is an important new technology in radiotherapy. Current evidence provides a limited indication for PBT. More robust prospective clinical trials are needed to determine the appropriate clinical setting for PBT. © 2012 Elsevier Ireland Ltd. All rights reserved.
Outcomes of stereotactic ablative radiotherapy for central lung tumours: A systematic reviewSashendra Senthi | Cornelis J A Haasbeek | Ben J. Slotman | Suresh Senan
Volume 106, Issue 3, March 2013, Pages 276-282
Background and purpose: Stereotactic ablative radiotherapy (SABR) has improved the survival for medically inoperable patients with peripheral early-stage non-small cell lung cancer (NSCLC). We performed a systematic review of outcomes for central lung tumours. Material and methods: The systematic review was performed following PRISMA guidelines. Survival outcomes were evaluated for central early-stage NSCLC. Local control and toxicity outcomes were evaluated for any centrally-located lung tumour. Results: Twenty publications met the inclusion criteria, reporting outcomes for 563 central lung tumours, including 315 patients with early-stage NSCLC. There was heterogeneity in the planning, prescribing and delivery of SABR and the common toxicity criteria used to define toxicities (versions 2.0-4.0). Tumour location (central versus peripheral) did not impact overall survival. Local control rates were ≥85% when the prescribed biologically equivalent tumour dose was ≥100 Gy. Treatment-related mortality was 2.7% overall, and 1.0% when the biologically equivalent normal tissue dose was ≤210 Gy. Grade 3 or 4 toxicities may be more common following SABR for central tumours, but occurred in less than 9% of patients. Conclusions: Post-SABR survival for early-stage NSCLC is not affected by tumour location. SABR achieves high local control with limited toxicity when appropriate fractionation schedules are used for central tumours. © 2013 Elsevier Ireland Ltd. All rights reserved.
The role of homologous recombination in radiation-induced double-strand break repairPenny A. Jeggo | Verena Geuting | Markus Löbrich
Volume 101, Issue 1, October 2011, Pages 7-12
DNA double-strand breaks (DSBs) represent the most biologically significant lesions induced by ionizing radiation (IR). HR is the predominant pathway for repairing one-ended DSBs arising in S-phase when the replication fork encounters single-stranded breaks or base damages. Here, we discuss recent findings that two-ended DSBs directly induced by X- or γ-rays in late S- or G2-phase are repaired predominantly by NHEJ, with HR only repairing a sub-fraction of such DSBs. This sub-fraction represents DSBs which localize to heterochromatic DNA regions and, which in control cells, are repaired with slow kinetics over many hours post irradiation. The observation that defined DSB populations are repaired by either NHEJ or HR suggests an assignment of specific tasks for each of the two processes. Furthermore, heavy ion induced complex DSBs, which are in general more slowly repaired than X- or γ-ray induced breaks, are nearly always repaired by HR independent of chromatin localization suggesting that the speed of repair is an important factor determining the DSB repair pathway usage. Finally, NHEJ and HR can, under certain conditions, also compensate for each other such that DSBs normally repaired by one pathway can undergo repair by the other if genetic failures necessitate the pathway switch. © 2011 Elsevier Ireland Ltd. All rights reserved.
Impact of 3D image-based PDR brachytherapy on outcome of patients treated for cervix carcinoma in France: Results of the French STIC prospective studyClaire Charra-Brunaud | Valentin Harter | Martine Delannes | Christine Haie-Meder | Philippe Quetin | Christine Kerr | Bernard Castelain | Laurence Thomas | Didier Peiffert
Volume 103, Issue 3, June 2012, Pages 305-313
Purpose: In 2005 a French multicentric non randomized prospective study was initiated to compare two groups of patients treated for cervix carcinoma according to brachytherapy (BT) method: 2D vs 3D dosimetry. The BT dosimetric planning method was chosen for each patient in each center according to the availability of the technique. This study describes the results for 705 out of 801 patients available for analysis. Patients and methods: For the 2D arm, dosimetry was planned on orthogonal X-Rays using low dose rate (LDR) or pulsed dose rate (PDR) BT. For the 3D arm, dosimetry was planned on 3D imaging (mainly CT) and performed with PDR BT. Each center could follow the dosimetric method they were used to, according to the chosen radioelement and applicator. Manual or graphical optimization was allowed. Three treatment regimens were defined: Group 1: BT followed by surgery; 165 patients (2D arm: 76; 3D arm: 89); Group 2: EBRT (+chemotherapy), BT, then surgery; 305 patients (2D arm: 142; 3D arm: 163); Group 3: EBRT (+chemotherapy), then BT; 235 patients, (2D arm: 118; 3D arm: 117). The DVH parameters for CTVs (High Risk CTV and Intermediate Risk CTV) and organs at risk (OARs) were computed as recommended by GYN GEC ESTRO guidelines. Total doses were converted to equivalent doses in 2 Gy fractions (EQD2). Side effects were prospectively assessed using the CTCAEv3.0. Results: The 2D and 3D arms were well balanced with regard to age, FIGO stage, histology, EBRT dose and chemotherapy. For each treatment regimen, BT doses and volumes were comparable between the 2D and 3D arms in terms of dose to point A, isodose 60 Gy volume, dose to ICRU rectal points, and TRAK. Dosimetric data in the 3D arm showed that the dose delivered to 90% of the High Risk CTV (HR CTV D90) was respectively, 81.2 Gy α/β10, 63.2 Gy α/β10 and 73.1 Gy α/β10 for groups 1, 2 and 3. The Intermediate Risk (IR) CTV D90 was respectively, 58.5 Gy α/β10, 57.3 Gy α/β10 and 61.7 Gy α/β10 for groups 1, 2 and 3. For the OARs, doses delivered to D2 cc ranged 60-70 Gy α/β3 for the bladder, 33-61 Gy α/β3 for the rectum, and 44-58 Gy α/β3 for the sigmoid according to the regimen. At 24 months, local relapse-free survival was 91.9% and 100% in group 1, 84.7% and 93% in group 2, 73.9% and 78.5% in group 3; grade 3-4 toxicity rate was 14.6% and 8.9% in group 1, 12.5% and 8.8% in group 2, and 22.7% and 2.6% in group 3 for 2D and 3D arm. Conclusion: This multicentric study has shown that 3D BT is feasible and safe in routine practice. It has improved local control with half the toxicity observed with 2D dosimetry. The combined treatment with radiotherapy and surgery was more toxic than definitive radiotherapy. For patients with advanced tumors, it is necessary to improve coverage of target volumes without raising toxicity. © 2012 Elsevier Ireland Ltd. All rights reserved.
Geometric accuracy of a novel gimbals based radiation therapy tumor tracking systemTom Depuydt | Dirk Verellen | Olivier Haas | Thierry Gevaert | Nadine Linthout | Michael Duchateau | Koen Tournel | Truus Reynders | Katrien Leysen | Mischa Hoogeman | Guy Storme | Mark De Ridder
Volume 98, Issue 3, March 2011, Pages 365-372
Purpose: VERO is a novel platform for image guided stereotactic body radiotherapy. Orthogonal gimbals hold the linac-MLC assembly allowing real-time moving tumor tracking. This study determines the geometric accuracy of the tracking. Materials and methods: To determine the tracking error, an 1D moving phantom produced sinusoidal motion with frequencies up to 30 breaths per minute (bpm). Tumor trajectories of patients were reproduced using a 2D robot and pursued with the gimbals tracking system prototype. Using the moving beam light field and a digital-camera-based detection unit tracking errors, system lag and equivalence of pan/tilt performance were measured. Results: The system lag was 47.7 ms for panning and 47.6 ms for tilting. Applying system lag compensation, sinusoidal motion tracking was accurate, with a tracking error 90% percentile E90% < 0.82 mm and similar performance for pan/tilt. Systematic tracking errors were below 0.14 mm. The 2D tumor trajectories were tracked with an average E90% of 0.54 mm, and tracking error standard deviations of 0.20 mm for pan and 0.22 mm for tilt. Conclusions: In terms of dynamic behavior, the gimbaled linac of the VERO system showed to be an excellent approach for providing accurate real-time tumor tracking in radiation therapy. © 2011 Elsevier Ireland Ltd. All rights reserved.
Breast-conserving therapy with partial or whole breast irradiation: Ten-year results of the Budapest randomized trialCsaba Polgár | János Fodor | Tibor Major | Zoltán Sulyok | Miklós Kásler
Volume 108, Issue 2, August 2013, Pages 197-202
Background and purpose To report the long-term results of a single-institution randomized study comparing the results of breast-conserving treatment with partial breast irradiation (PBI) or conventional whole breast irradiation (WBI). Patients and methods Between 1998 and 2004, 258 selected women with pT1 pN0-1mi M0, grade 1-2, non-lobular breast cancer without the presence of extensive intraductal component and resected with negative margins were randomized after BCS to receive 50 Gy WBI (n = 130) or PBI (n = 128). The latter consisted of either 7 × 5.2 Gy high-dose-rate (HDR) multi-catheter brachytherapy (BT; n = 88) or 50 Gy electron beam (EB) irradiation (n = 40). Primary endpoint was local recurrence (LR) as a first event. Secondary endpoints were overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS), and cosmetic results. Results After a median follow up of 10.2 years, the ten-year actuarial rate of LR was 5.9% and 5.1% in PBI and WBI arms, respectively (p = 0.77). There was no significant difference in the ten-year probability of OS (80% vs 82%), CSS (94% vs 92%), and DFS (85% vs 84%), either. The rate of excellent-good cosmetic result was 81% in the PBI, and 63% in the control group (p < 0.01). Conclusions Partial breast irradiation delivered by interstitial HDR BT or EB for a selected group of early-stage breast cancer patients produces similar ten-year results to those achieved with conventional WBI. Significantly better cosmetic outcome can be achieved with HDR BT implants compared with the outcome after WBI. © 2013 Elsevier Ireland Ltd. All rights reserved.
Gradient-based delineation of the primary GTV on FDG-PET in non-small cell lung cancer: A comparison with threshold-based approaches, CT and surgical specimensMarie Wanet | John Aldo Lee | Birgit Weynand | Marc De Bast | Alain Poncelet | Valérie Lacroix | Emmanuel Coche | Vincent Grégoire | Xavier Geets
Volume 98, Issue 1, January 2011, Pages 117-125
Purpose: The aim of this study was to validate a gradient-based segmentation method for GTV delineation on FDG-PET in NSCLC through surgical specimen, in comparison with threshold-based approaches and CT. Materials and methods: Ten patients with stage I-II NSCLC were prospectively enrolled. Before lobectomy, all patients underwent contrast enhanced CT and gated FDG-PET. Next, the surgical specimen was removed, inflated with gelatin, frozen and sliced. The digitized slices were used to reconstruct the 3D macroscopic specimen. GTVs were manually delineated on the macroscopic specimen and on CT images. GTVs were automatically segmented on PET images using a gradient-based method, a source to background ratio method and fixed threshold values at 40% and 50% of SUV max. All images were finally registered. Analyses of raw volumes and logarithmic differences between GTVs and GTV macro were performed on all patients and on a subgroup excluding the poorly defined tumors. A matching analysis between the different GTVs was also conducted using Dice's similarity index. Results: Considering all patients, both lung and mediastinal windowed CT overestimated the macroscopy, while FDG-PET provided closer values. Among various PET segmentation methods, the gradient-based technique best estimated the true tumor volume. When analysis was restricted to well defined tumors without lung fibrosis or atelectasis, the mediastinal windowed CT accurately assessed the macroscopic specimen. Finally, the matching analysis did not reveal significant difference between the different imaging modalities. Conclusions: FDG-PET improved the GTV definition in NSCLC including when the primary tumor was surrounded by modifications of the lung parenchyma. In this context, the gradient-based method outperformed the threshold-based ones in terms of accuracy and robustness. In other cases, the conventional mediastinal windowed CT remained appropriate. © 2010 Elsevier Ireland Ltd. All rights reserved.
The influence of HPV-associated p16-expression on accelerated fractionated radiotherapy in head and neck cancer: Evaluation of the randomised DAHANCA 6&7 trialPernille Lassen | Jesper G. Eriksen | Annelise Krogdahl | Marianne Hamilton Therkildsen | Benedicte P. Ulhøi | Marie Overgaard | Lena Specht | Elo Andersen | Jørgen Johansen | Lisbeth J. Andersen | Cai Grau | Jens Overgaard
Volume 100, Issue 1, July 2011, Pages 49-55
Background and purpose: Tumour HPV-positivity is a favourable prognostic factor in the radiotherapy of HNSCC, but the optimal radiotherapy regimen for HPV-positive HNSCC is not yet defined. Reducing overall treatment time is known to improve outcome in the radiotherapy of HNSCC as was also demonstrated in the randomised DAHANCA 6&7 trial. We aimed to assess the influence of tumour HPV-status, expressed by p16, on the response to accelerated fractionated radiotherapy in HNSCC through evaluation of the DAHANCA 6&7 trial. Materials and methods: Immunohistochemical detection of HPV-associated p16-expression was performed on FFPE-pre-treatment tumour-tissues from 794 patients enrolled in the DAHANCA 6&7 trial. The influence of tumour p16-status on loco-regional tumour control and survival as a function of fractionation schedule (5 Fx/week vs 6 Fx/week) was evaluated 5 years after the completion of radiotherapy. Results: The significant and independent prognostic value of tumour p16-positivity in HNSCC radiotherapy was confirmed, with adjusted hazard ratios (HR) of 0.58 [0.43-0.78], 0.47 [0.33-0.67] and 0.54 [0.42-0.68] for loco-regional control, disease-specific and overall survival, respectively. Accelerated radiotherapy significantly improved loco-regional tumour control compared to conventional radiotherapy, adjusted HR: 0.73 [0.59-0.92] and the benefit of the 6 Fx/week regimen was observed both in p16-positive (HR: 0.56 [0.33-0.96]) as well as in p16-negative tumours (HR: 0.77 [0.60-0.99]). Disease-specific survival was also significantly improved with accelerated radiotherapy in the group of p16-positive tumours (adjusted HR: 0.43 [0.22-0.82]). Conclusion: Accelerated radiotherapy significantly improves outcome in HNSCC compared to conventional fractionation. The observed benefit is independent of tumour p16-status and the use of a moderately accelerated radiotherapy regimen seems advantageous also for HPV/p16-positive HNSCC. © 2011 Elsevier Ltd. All rights reserved.
Twelve-year clinical outcomes and patterns of failure with accelerated partial breast irradiation versus whole-breast irradiation: Results of a matched-pair analysisChirag Shah | John Vito Antonucci | John Ben Wilkinson | Michelle Wallace | Mihai Ghilezan | Peter Chen | Kenneth Lewis | Christina Mitchell | Frank Vicini
Volume 100, Issue 2, August 2011, Pages 210-214
Background and Purpose: To compare 12-year outcomes of accelerated partial breast irradiation (APBI) versus whole-breast irradiation (WBI) in patients treated with breast conservation. Materials and Methods: A matched-pair analysis was performed using 199 patients receiving WBI and 199 patients receiving interstitial APBI. Match criteria included tumor size, age, nodal status, ER status, and the use of adjuvant hormonal therapy. Patterns of failure and efficacy of salvage treatments were examined. Results: No differences were seen in the 12-year rates of local recurrence (3.8% vs. 5.0%, p = 0.40), regional recurrence (0% vs. 1.1%, p = 0.15), disease free survival (DFS) (87% vs. 91%, p = 0.30), cause-specific survival (CSS) (93% vs. 95%, p = 0.28), or overall survival (OS) (78% vs. 71%, p = 0.06) between the WBI and APBI groups, respectively. The rate of distant metastases was lower in the APBI group (10.1% vs. 4.5%, p =.05). Following LR, no difference in outcome was seen between the two groups with 5 year post-LR rates of DFS (80% vs. 86%, p = 0.55), CSS (88% vs. 75%, p = 0.77), and OS (88% vs. 75%, p = 0.77), respectively. Conclusions: With 12-year follow-up, APBI produced outcomes equivalent to WBI. Following LR, patients treated with APBI also had similar failure patterns to those managed with WBI. © 2011 Elsevier Ireland Ltd. All rights reserved.
Gene expression classifier predicts for hypoxic modification of radiotherapy with nimorazole in squamous cell carcinomas of the head and neckKasper Toustrup | Brita Singers Sørensen | Pernille Lassen | Carsten Wiuf | Jan Alsner | Jens Overgaard
Volume 102, Issue 1, January 2012, Pages 122-129
Purpose: To validate the predictive impact of a hypoxia gene expression classifier in identifying patients with head and neck squamous cell carcinoma (HNSCC) having benefit from hypoxic modification of radiotherapy. Patients and methods: Gene expressions were quantified from formalin-fixed, paraffin-embedded tumour biopsies of 323 HNSCC patients randomized for placebo or nimorazole in conjunction with radiotherapy in the DAHANCA 5 study. Tumours were classified as either "more" or "less" hypoxic with a classifier constituting of 15 hypoxia responsive genes. The predictive impact was evaluated by analysing the response to nimorazole vs. placebo in terms of loco-regional tumour control (LRC) and disease-specific survival (DSS) in the two classified groups. Results: Hundred and fourteen patients (35%) were classified as having "more" hypoxic tumours. These patients had a significant benefit of hypoxic modification with nimorazole compared with placebo in terms of LRC (5-year actuarial values 49% vs. 18%; p = 0.001) and DSS (48% vs. 30%; p = 0.04). "Less" hypoxic tumours had no significant effect of hypoxic modification (LRC: 50% vs. 44%; p = 0.39, DSS: 57% vs. 51%; p = 0.49) and generally an outcome, which was similar to "more" hypoxic tumours treated with nimorazole. In contrast to HPV-negative tumours, HPV-positive tumours had a substantially better outcome in response to radiotherapy, which was irrespective of hypoxic modification. Conclusions: A predictive 15-gene hypoxia classifier could identify patients associated with improved outcome after combining radiotherapy with hypoxic modification and underlines the relevance of such therapy. The impact of the classifier was limited to HPV-negative tumours. © 2011 Elsevier Ireland Ltd. All rights reserved.
Radiographic changes after lung stereotactic ablative radiotherapy (SABR) - Can we distinguish recurrence from fibrosis? A systematic review of the literatureKitty Huang | Max Dahele | Suresh Senan | Matthias Guckenberger | George B. Rodrigues | Aaron Ward | R. Gabriel Boldt | David A. Palma
Volume 102, Issue 3, March 2012, Pages 335-342
Background: Changes in lung density on computed tomography (CT) are common after stereotactic ablative radiotherapy (SABR) and can confound the early detection of recurrence. We performed a systematic review to describe post-SABR findings on computed tomography (CT) and positron-emission tomography (PET), identify imaging characteristics that predict recurrence and propose a follow-up imaging algorithm. Methods: A systematic review was conducted of studies providing detailed radiologic descriptions of anatomic and metabolic lung changes after SABR. Our search returned 824 studies; 26 met our inclusion criteria. Data are presented according to PRISMA guidelines. Results: Acute changes post-SABR predominantly appear as consolidation or ground glass opacities. Late changes often demonstrate a modified conventional pattern of fibrosis, evolving beyond 2 years after treatment. Several CT features, including an enlarging opacity, correlate with recurrence. Although PET SUVmax may rise immediately post-SABR, an SUVmax ≥ 5 carries a high predictive value of recurrence. Conclusions: CT density changes are common post-SABR. The available evidence suggests that recurrent disease should be suspected if high-risk CT changes are seen with SUVmax ≥ 5 on PET. Further studies are needed to validate the predictive values of such metrics, and for advanced analysis of CT changes to allow early detection of potentially curable local recurrence. © 2011 Elsevier Ireland Ltd. All rights reserved.
Hypoxia imaging with [F-18] FMISO-PET in head and neck cancer: Potential for guiding intensity modulated radiation therapy in overcoming hypoxia-induced treatment resistanceKristi Hendrickson | Mark Phillips | Wade Smith | Lanell Peterson | Kenneth Krohn | Joseph Rajendran
Volume 101, Issue 3, December 2011, Pages 369-375
Background and purpose: Positron emission tomography (PET) imaging with [F-18] fluoromisonidazole (FMISO) has been validated as a hypoxic tracer [1,2]. Head and neck cancer exhibits hypoxia, inducing aggressive biologic traits that impart resistance to treatment. Delivery of modestly higher radiation doses to tumors with stable areas of chronic hypoxia can improve tumor control [3]. Advanced radiation treatment planning (RTP) and delivery techniques such as intensity modulated radiation therapy (IMRT) can deliver higher doses to a small volume without increasing morbidity. We investigated the utility of co-registered FMISO-PET and CT images to develop clinically feasible RTPs with higher tumor control probabilities (TCP). Materials and methods: FMISO-PET images were used to determine hypoxic sub-volumes for boost planning. Example plans were generated for 10 of the patients in the study who exhibited significant hypoxia. We created an IMRT plan for each patient with a simultaneous integrated boost (SIB) to the hypoxic sub-volumes. We also varied the boost for two patients. Result: A significant (mean 17%, median 15%) improvement in TCP is predicted when the modest additional boost dose to the hypoxic sub-volume is included. Conclusion: Combined FMISO-PET imaging and IMRT planning permit delivery of higher doses to hypoxic regions, increasing the predicted TCP (mean 17%) without increasing expected complications. © 2010 Elsevier Ireland Ltd. All rights reserved.
Specific inhibition of carbonic anhydrase IX activity enhances the in vivo therapeutic effect of tumor irradiationLudwig Dubois | Sarah Peeters | Natasja G. Lieuwes | Nele Geusens | Anne Thiry | Simon Wigfield | Fabrizio Carta | Alan McIntyre | Andrea Scozzafava | Jean Michel Dogné | Claudiu T. Supuran | Adrian L. Harris | Bernard Masereel | Philippe Lambin
Volume 99, Issue 3, June 2011, Pages 424-431
Background and purpose: Carbonic anhydrase (CA) IX expression is increased upon hypoxia and has been proposed as a therapeutic target since it has been associated with poor prognosis, tumor progression and pH regulation. The aim of this study was to evaluate the antitumor activity of a high CAIX-affinity indanesulfonamide (11c) combined with irradiation, compared with the general CA inhibitor acetazolamide (AZA). Material and methods: HT-29 carcinoma cells with or without (genetic knockdown, KD) CAIX expression were incubated with 11c/AZA under different oxygen levels and proliferation, apoptosis and radiosensitivity were evaluated. 11c/AZA was administered intravenously (1×/day; 5 days) to tumor-bearing mice and tumor irradiation (10 Gy) was performed at day 3 of the injection period. Tumor growth and potential treatment toxicity were monitored (3×/week). Results: Treatment with 11c/AZA alone resulted in tumor regression, which was further increased in CAIX expressing cells by combining 11c with irradiation. AZA demonstrated also an additional effect in the KD tumors when combined with irradiation. CAIX inhibition in vitro significantly reduced proliferation and increased apoptosis upon hypoxia exposure without affecting intrinsic radiosensitivity. Conclusions: Specific inhibition of CAIX activity enhanced the effect of tumor irradiation and might, therefore, be an attractive strategy to improve overall cancer treatment. © 2011 Elsevier Ireland Ltd. All rights reserved.


text: Dragon Apartments - Hostel is in the heart of Krakow, walking distance from Art Agenda Nova and Stary Kleparz. This hostel is close to Main Market Square and Wawel Castle. Make yourself at home in one of the 14 guestrooms, featuring kitchens. Complimentary wireless Internet access keeps you connected, and 52-inch LCD televisions are provided for your entertainment. Conveniences include coffee/tea makers, housekeeping is provided weekly, and microwaves can be requested. Make use of convenient amenities such as complimentary wireless Internet access, concierge services, and a television in the lobby. Continental breakfasts are available daily for a fee. Featured amenities include express check-in, express check-out, and dry cleaning/laundry services. For a surcharge, guests may use a roundtrip airport shuttle (available on request) and a train station pick-up service.

subset: commoncrawl


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Welsh Water Contact Number
0843 557 5246
If Welsh Water is your water provider and you are experiencing some kind of problem with your water supply, such as discoloured water or no water at all, you will want to speak to customer services. Number Contact can transfer you to the team at Welsh Water contact.
Why would I need to call Welsh Water contact?
- To get assistance if your water supply has stopped.
- To pay your bill over the telephone.
- To report a leakage or enquire about ongoing water works in your area.
Welsh Water services
Welsh Water is also known as Dwr Cymru, and is the main water supplier for most of Wales. If you wish to find out about your water supply or report a problem, call Number Contact to be put through to the team at Welsh Water contact. Welsh Water aims to provide residents of Wales with clean and safe drinking water as well as effectively managing wastewater throughout Wales. If you wish to find out about the quality of your drinking water or get information on how wastewater is treated, visit the website. From there, you can also report a leak, pay your bill and tell Welsh Water that you are moving house as well as get more information on how having a water meter can save you money.
About Welsh Water
Welsh Water originated in 1989 following the privatisation of water supply and waste water treatment. It had origins in the Welsh National Water Development Authority which was created itself by the 1973 restructuring of the water industry in England and Wales. It took over several public sector undertakings such as South West Wales River Authority, Usk River Authority and much more. Today, Welsh Water is owned by Glas Cymru. To find out more about Welsh Water, visit the website.


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JA Brisk
Divina Pharm
10 Hair Styling Methods For Anybody With A Hair
While explore hairstyles, women entwine, pin up, color as well as crinkle their hair. Like I discuss detailed in The Curly Hair Book, you must have your hair damp when you wish to style your hair generally; nevertheless, to make use of a hair straightener, you intend to have your hair fully dried. Ahead, locate seven types of designs you can achieve with a curling iron, plus the particular gadgets that function very well for each. Merely hold a thick part of the hair from the crown section and even iron your hair towards the ceiling (higher instructions) to obtain quantity. For crinkling, you simply curl at the top and also slower drag it down - sort of like curling ribbon on a gift or balloon. After using hair chalk, look at your strands with a level iron making the shade super dynamic! Find out the trade secrets directly from the hairdressing market specialists and also master the techniques to stunning hair with our hair guide video clips. So it needs to be tiny sufficient to where you can actually twist the hair right into a curl.
Divide your hair in to 6-8 equal parts as well as apply a hair lotion aftered by a hair spray as well as begin making use of the straightener on one side of the hair and even hair brush on the other side to get the bested bend appearance. Last, broken hair could do much more than healthy and balanced hair can, so get some blonde highlights put in by a professional! Initially, haze dry hair with a salt spray, like Tigi Catwalk Procedure Series Salt Spray, $13.52,, then freely braid a couple of one-inch sections of hair around your face. Beginning with a flat iron that is somewhat rounded around home plate-- I am making use of a chi in this demonstration.
While curling with a flat iron needs a little bit of technique as soon as you become it, it's very difficult to go wrong. To make sure straight strands, attempt using Chi Straight Guard Smoothing Styling Lotion ($15;) before you begin styling. Standard irons with flexible temperature allow you choose the right warmth for your hair type and also design. Wrap your hair in a towel for 15 to 20 mins before shampooing and also beginning your straightening procedure. Secure your hair straightener into the braids as well as slowly slide them along each one.
So as opposed to immediately putting straightened hair into a braid or clip, enable your hair to cool down after you iron it. Obtain even more compared to ever before from your Save your favorite write-ups for fast access to the specialist suggestions and tricks that talk to you - and also the items you need to become the appearances! When expanding your hairdo, having the appropriate kind of level iron can conserve you money and also time. These are merely 3 ideas from the tons of different ways to do fancy techniques with your flat iron.
Simply in case you wish to get back to the essentials, we believed we would certainly share a few quick tips on how to effectively standard iron your hair. When styling with a level iron (or any heat, truly), always use a heat protectant prior to you begin styling. To produce an amazing kink like Jennifer Hudson's, beginning with straight locks, get a
part of hair as well as place your standard iron at the origin. Before you start using your level iron, make sure it's heated up and also ready-to-go. Sandwich your hair between 2 sticky items as well as utilize a level iron to seal the bond, which includes instantaneous volume or size.
Where you begin on your hair (in the direction of your scalp or in the direction of the ends), exactly how gradually you relocate the standard iron, as well as just how much you turn the flat iron. Keeping the iron on that half-turn angle, slowly move it down the hair shaft to the end of the hair. Anyhow, for this design all you need to do is to grab one inch part of your hair as well as place your level iron at the root. Heat-protectant spray as well as other styling products you put on your hair could-- and even will certainly-- develop on your flat iron.
As we mentioned earlier, warmth protectants guard your hair against damage as well as makes your hair smoother, shinier as well as the results of your flat iron last longer. Our curling irons, on the other hand, stay tucked away under our sinks, just to be pulled out when we desire, well, curls. When making use of a crinkling iron to curl your hair, it is improve to start at the middle of your hair instead of the end. If your curl does not look this curly: glide the flat iron much more slowly down the hair strand, offering it longer time to get each component of the hair warm sufficient. Ensure that your hair is detangled sufficient to utilize your flat iron to streamlined it down.
This is particularly essential for anyone who uses a flat iron day-to-day or those of us that have to transform our standard iron to 450 levels. I have pin straight hair that's curl resistant as well as due to the fact that it's heavily layered, it's really difficult to crinkle with a crinkling iron. Smoke and even sizzle is not music to your ears - If you see smoke, that suggests the level iron is way as well very hot as well as it should be declined. Then utilize your flat iron as you typically would, except rather than going directly down, slowly turn the iron down and also under your ends.
Should you have any questions relating to exactly where in addition to how you can work with
, you possibly can e mail us from the internet site. Place hairspray on parts quickly prior to you crinkle them if your hair doesn't crinkle quickly or doesn't hold a curl. There is nothing even more sad compared to spending a hr crinkling your hair, only for all the swirls to befall thirty minutes later! Throughout the Appeal Buzz segment Jason Stanton, hairstylist for Solano, revealed us exactly how he produces structure. On the planet of hot devices, the level iron has actually constantly seemed like the workhorse of the bunch. My hair will not hold a crinkle for more than a couple of hours, yet I purchased some hair extensions (real hair) to attempt them out and even they hold curl for days. It will certainly assist your hair versus breakage, battle frizz and also keeps your hair healthy. Make use of a good ceramic BEVELED APARTMENT IRON to develop SUBTLE WAVES like the collar, the cuffs, or a hem.
10 Hair Styling Methods For Anybody With A Hair


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The best way to get something is to ask for it. In words. Whether it be a user interface such as Siri, a way for doctors to speed their work and reduce errors caused by their famously bad handwriting, or a way to translate text to the spoken word, voice technology is something that a lot of people are, well, talking about.
From giants such as Nuance to specialists such as Canonical, the integration of speech into enterprise IT and telecommunications is growing and becoming more sophisticated. While much of the action is on the mobile front, the art and science of providing voice capabilities to stationary devices is also growing.
Related Topics : Vulnerabilities and Patches, Resellers, Broadcom, Broadband Services, Supercomputing
Digital innovation is by far the biggest influencer, changing the way we do just about everything, from shopping to communication to running a business. ... More >>
The real value that the Internet of Things brings is at the intersection of gathering data and leveraging it. ... More >>
Enterprise social collaboration solutions are most successful when they contribute to business value and benefits that address company goals. ... More >>


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Written on: 29/02/2012 by Iain67 (2 reviews written)
We booked with Broadway Travel August 2011 a 2 week holiday at Sharm el Sheik (Egypt). Their telephone sales advisor could not have been more helpful or knowlegable. We flew Thomson Airlines from East Midlands. Most bizarrely the same holiday with Thomson Holidays using their plane was £700 more staying at the same hotel.
All the tickets and documantation arrived in plenty of time for our departure.
The hotel we were booked in was a decent offering listed 5* which it probably was not.
As rated by our community of reviewers
" Could not be better " Read More
" Easy to book online. " Read More
" Fuerteventura holiday 2016 " Read More
" Corfu Late Sun " Read More
Written by John7559
" Hilton Garden Inn, Venice/Mestre " Read More


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Who's New for May 2
May 12, 2014
Born at North Colorado Medical Center April 24 to:
Mario and Christine Granados, both of Milliken, a daughter, Lily Violet Granados. Grandparents are Lisa Cossio, Jose G. Granados and Maria C. Granados, all of Milliken
Born at North Colorado Medical Center April 26 to:
Angelica Ramirez and Desi Barrera Jr., both of Greeley, a daughter, Adalee Jean Barrera. Grandparents are Norma J. Garcia of Denver, Dean Ramirez of Minnesota, Velma Barrera of Alto Bonito, Texas and Desi Barrera of Rio Grande City, Texas
Whitney and Kendal Staley, both of Fort Morgan, a son, Cole Ray Staley. Grandparents are Don and Melinda Fearhot and Mike and Rhonda Staley, all of Fort Morgan


text:
Brennen Beyer
- CollegeMichigan Wolverines
- PositionDEFENSIVE END
- HometownCanton, MI
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Big Ten Wednesday mailblog
Coming at you on Hump Day. As a reminder, we're taking more of your Twitter questions for the mailblog, so keep sending them in! Find us on Twitter here.about 832 days ago | Adam Rittenberg | ESPN.com
Preseason position preview: DL
You want to win in the Big Ten? Then you'd better have a strong defensive line.Being stout up front and strong enough to stop the run has long been a staple of success in this league.about 832 days ago | Brian Bennett | ESPN.com
Michigan has high hopes for D-line
ANN ARBOR, Mich. -- For many months, there has been hand-wringing and consternation about the state of Michigan's offensive line. But what about the other side of the trenches?about 896 days ago | Brian Bennett | ESPN.com
Post-spring roundtable: East Division
Spring practice in the Big Ten has sadly come to an end, and we're both back home after some trips around the conference. Wednesday, we shared out thoughts on the Big Ten's West Division, and now it's time to turn our focus to the beast known as the East.about 908 days ago | Adam Rittenberg and Brian Bennett | ESPN.com
Michigan spring wrap
The spring workouts are in the books and the long offseason has arrived. But before diving into summer and the painful wait for football to return, we're taking a look back at the developments from March and April and sneaking a peek at what to expect in the fall for Michigan.about 911 days ago | Brian Bennett | ESPN.com
Spring game recap: Michigan
Spring (practice) has officially sprung for Michigan, which became the first Big Ten team to hold its spring game on Saturday at the Big House.An estimated crowd of 15,000 took in the festivities, which included a non-scoring scrimmage.about 932 days ago | Brian Bennett | ESPN.com
Big Ten Tuesday mailblog
Spring practice is in full swing around the Big Ten, and we've got you covered. Be sure to check us out on Twitter.Mail call ...Lance from Mooresville, N.about 945 days ago | Adam Rittenberg | ESPN.com
The good, the bad, the future: SAM LB
At this time last year, prospects for the SAM linebacker position were great. But by the end of spring football, there were more questions and fears than anything else because of Jake Ryans ACL tear.about 1014 days ago | Chantel Jennings | ESPN.com
The good, the bad, the future: D-line
The offensive and defensive lines underachieved this season for Michigan. For a program that wants its identity to be in the trenches, this wasnt exactly a poster year.about 1016 days ago | Chantel Jennings | ESPN.com
Coulda, shoulda, woulda: Brennen Beyer
Hindsight is 20/20, and its especially hard to draw conclusions about what couldve or shouldve happened when an injury is involved.about 1037 days ago | Chantel Jennings | ESPN.com
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With 166 years of experience we know the trends that are going to continue to make your kitchen the heart of the home, and we have awards to prove it!Read more
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Code: KCNSSPLAT
Can you tell me what the mesh material is used with this product. Who would supply an order of approximatly 60mtr² cut to a 210 x 60mm rectangular unit?
Any ideas you have would be welcome.
Thank You.
Posted by Colin Pinnegar (13th March 2014)
Overall Rating: 5/5
Hi Colin,
thank you for your message. The material is a non-stick coated black steel wire mesh.
Unfortunalety we can't help you with the supplier of the flat material as we're sourcing this product as a whole.
Thanks again for your feedback and we hope we could help.
Reply from Kitchen Craft (13th March 2014)
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If I will say that Relocation can be a fun, than many of you will not agree with that. This is a general human behavior that we consider relocation as the most complex process and specially packing of the goods. By giving a eye all around our house we actually get confused as from where to start all this and this thinking tend us to belie that it is really going to be a tough job for us. But there are few easy tricks that can actually make the relocation havoc a simple business for all.
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Home > The Attacat Brain Attacats Twitter Weekly Updates for 2010-12-17 Thought from Attacat_Ben Dec 17, 2010 0 @MarkJWBoyd not sure about that but we have certainly added a few new recruits to the ranks recently! # 0 Add a comment Leave a Reply Cancel reply Your email address will not be published. Required fields are marked * Name * Email * Website Comment You may use these HTML tags and attributes:   <acronym title="">
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8" white cake with BC. My writing is a little slanted!!
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Movie Review: 'Forrest Gump' in ImaxAlthough you certainly don't need to see it on an Imax screen to enjoy or appreciate this celebrated movie, that's exactly where you'll find it as of this week.
Bill Wine's Oscar Predictions: Best Actress, Supporting ActressBill Wine gives us his picks for the best actress and best supporting actress categories in the 2013 Academy Awards.
Movie Review: 'Lincoln'"Lincoln" brings the iconic Abraham Lincoln down to earth, but without diminishing him in any way.
Movie Review: The Amazing Spider-Man'The Amazing Spider Man' is another acrobatic, angst-ridden, arachnoidy thriller, a quick relaunch of the superhero franchise.


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Application for 2016-2017 MHS Membership
Applications will be accepted through Wednesday, April 6, 2016, for the class of 2017 and 2018. Use the attached application form on this page. ALL APPLICANTS ARE REQUIRED TO COMPLETE 40 HOURS OF COMMUNITY SERVICE FROM APRIL 1, 2015 THROUGH APRIL 1, 2016. THIS IS THE FINAL OPPORTUNITY FOR THE CLASS OF 2017 TO APPLY!
Current MHS members DO NOT need to apply again.
The MHS induction ceremony will be held in May of 2016 for all current applicants.


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I think this is a great way to end this blog. I got married, My best friend is getting hitched, and I've moved on to the next chapter in my life and had a baby. Now that I have a little ladybug to take care of you will see me mostly on my baby blog.
It's been a great journey and I wish all the weddingbee'ers and readers much love and happiness.
Mrs Ladybug aka Susan
Mrs. Ladybug
- Location:
- New York/Philadelphia
- Occupation:
- Full-time blogger from 7 pm to 12 am
- Wedding Date:
- April 2006
- Venue:
- Ballroom at the Ben, Philadelphia
Related Posts
I'm a Sadie…The Horseshoes Got Hitched!@ 10:24 am
Ocean Size Love: The Gang's All Here!@ 10:11 am
We Blue Moons Got Hitched!@ 11:23 am
Our Wedding Vows@ 11:21 am


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Bostrychia bocagei
|Scope: Global
|Scientific Name:
|Bostrychia bocagei
|Species Authority:
|(Chapin, 1923)
Common Name(s):
|Taxonomic Source(s):
|del Hoyo, J., Collar, N.J., Christie, D.A., Elliott, A. and Fishpool, L.D.C. 2014. HBW and BirdLife International Illustrated Checklist of the Birds of the World. Lynx Edicions BirdLife International.
|Taxonomic Notes:
|Bostrychia olivacea (Sibley and Monroe 1990, 1993) has been split into B. olivacea and B. bocagei following Collar and Stuart (1985). Dwarf Olive Ibis Bostrychia bocagei of São Tomé differs from African Olive Ibis B. olivacea of West and Central Africa in size (wing of cupreipennis 309-355 mm, bill 83-94 mm, tarsus 58-70 mm, tail 125-133 mm [measurements of Príncipe race rothschildi similar]; wing of bocagei 248 mm [n=5] [i.e. 75%], bill 73 mm [82%], tarsus 52 mm [81%], tail 95 mm [74%]), bill colour (pale brown with pale red on culmen and tip vs all pale to brick red in rothschildi), and coloration of upperparts (lacking greenish and some bronze sheen of other races), plus an evident but still poorly documented difference in voice (rothschildi producing a typical "HAAN-ha HAAN-ha" at dawn and dusk, bocagei remaining mostly silent but occasionally delivering a more equally stressed "kàh-gàh kàh-gàh"). There is good precedent for allowing its specific status (i.e. Chapin 1923, Amadon 1953, de Naurois 1973).
|Identification information:
|60-65 cm. Small forest ibis. Adult has dull olive head and body with slightly bronzed mantle and wing-coverts. Dark area around eyes and base of bill. Voice Various coughed grunts when disturbed and harsh honking when going to roost.
|Red List Category & Criteria:
|Critically Endangered C2a(ii) ver 3.1
|Year Published:
|Date Assessed:
|BirdLife International
|Symes, A.
|Carvalho, M., Gascoigne, A., Melo, M., d'Assis Lima, S. & de Lima, R.
|Bird, J., Butchart, S., Ekstrom, J., Pilgrim, J., Symes, A., Taylor, J., Allinson, T & Ashpole, J
This species is classified as Critically Endangered owing to its extremely small population which is declining as a result of hunting pressure.
|Previously published Red List assessments:
|Range Description:
|This species is endemic to São Tomé, São Tomé and Príncipe, where it is confined to the catchments of the São Miguel, Xufexufe and possibly the Quija rivers in the south-west, and along the Io Grande, Ana Chaves and Lembá rivers in the centre of the island (Ward-Francis et al. 2015). It was known only from historical records and anecdotal evidence from hunters until a confirmed sighting in the valley of the rio Ana Chaves, in 1990 (Atkinson et al. 1991). More records followed: birds were seen in 1996; two pairs, an individual and two nests were seen near the basins of the Rios Ió Grande (200 m asl) and Martim Mendes (100 m asl) in May 1997 in an area where hunters reported killing 16 of the birds 6 months previously (S. d'Assis Lima in litt. 1998); and during survey work in Ribeira Peixe in 2007 (Olmos and Turshak 2007). More recent fieldwork resulted in 57 observations, including two nests with brooding females, in primary forest in the Monte Carmo area (Maia and Gascoigne in litt. 2010). A survey in July-September 2014 observed 48 individuals and one record of nest building (Ward-Francis et al. 2015). The most recent estimation suggests that the population is >50 individuals but remains extremely small (M. Melo in litt. 2006). It is apparently relatively widely, if thinly, distributed in the south. There is one historical record from the north of the island, but no suitable habitat remains there (Christy and Clarke 1998).
|Countries occurrence:
Native:Sao Tomé and Principe (Sâo Tomé)
|Additional data:
|Range Map:
|Click here to open the map viewer and explore range.
|The most recent population estimate indicates that it is extremely small, and is best placed in the band 50-249 mature individuals (M. Melo in litt. 2006). This equates to 75-374 individuals in total, rounded here to 70-400 individuals.
Trend Justification: Hunting pressure is suspected to be high with a recent report of 16 individuals being killed (S. d'Assis Lima in litt. 2006).
|Current Population Trend:
|Additional data:
|Habitat and Ecology:
|Behaviour: This species is presumed to be sedentary (del Hoyo et al. 1992). Birds usually occur singly or in pairs (Borrow and Demey 2001) but roost together at night and can be identified as they call when flying to and from the roost (M. Melo in litt. 2006).
Habitat: The species is confined to primary forest below 750 m (Ward-Francis et al. 2015), although suitable habitat could extend up to 800 m. However, it has been found most frequently in recent years at the border between primary and secondary forest, sometimes near palm plantations (M. Melo in litt. 2006). It appears to prefer flatter areas (Ward-Francis et al. 2015). Recent observations from Monte Carmo were from mature or old second-growth forest (Olmos and Turshak 2010). It forages on lowland forest floors on areas of bare ground or where there exists a sparse undergrowth of herbaceous plants, bracken and moss, a covering of rocks and large stones or around large trees with extensive buttresses (Christy and Clarke 1998, Olmos and Turshak 2010, Ward-Francis et al. 2015). It is especially found in areas where the ground has been disturbed by wild pigs or in swampy areas bordering watercourses or small oxbow lakes (Atkinson et al. 1991, Christy and Clarke 1998, Borrow and Demey 2001, Olmos and Turshak 2010).
Diet: Its diet consists of invertebrates, snails and slugs (Christy and Clarke 1998).
Breeding: It breeds during the rainy season (Ward-Francis et al. 2015). A nest was found in 1997 in a tree overhanging water (S. d'Assis Lima in litt. 1998) and a nest found in 2009 was also in a tree (BirdLife International 2008).
|Continuing decline in area, extent and/or quality of habitat:
|Generation Length (years):
|Movement patterns:
|Not a Migrant
|Congregatory (and dispersive)
|Major Threat(s):
Historically, large areas of lowland forest were cleared for cocoa plantations. Today, land privatisation is leading to an increase in the number of small farms and the clearance of trees (M. Melo in litt. 2006). This does not currently affect primary forest, but may be a threat in the future (A. Gascoigne in litt. 2000). Agricultural encroachment in the more accessible areas of Obô Natural Park was evident in 2007 and 2008, and hunting and palm-wine harvesting were widespread (Olmos and Turshak 2007, 2010), with shelters constructed inside the park (Olmos and Turshak 2010). Hunting may be the most serious current threat; the species is apparently very desirable for its meat and reports include 16 birds being killed in 1996-1997 (S. d'Assis Lima in litt. 2006), and six birds killed on a single occasion by one hunter (del Hoyo et al. 1992). Hunting pressure is believed to be increasing in the Monte Carmo area of the Obô Natural Park, one of the main strongholds for the species, and a group of hunters were found with at least one ibis in April 2011 (R. Grimmett in litt. 2011, Anon. 2011). A recent survey revealed that the extent of hunting was much greater than previously thought. However generally the species was not the target of hunters (whose main quarry was introduced pigs) and was instead taken opportunistically but the survey identified at least one exception where local villagers actively hunt the species (Ward-Francis et al. 2015).
Plans to develop coffee plantations and restore and extend 630 ha of abandoned palm-oil plantations (to cover more than 2,000 ha; ready for harvest in 2013) in the vicinity of the core zone of Obô Natural Park and encroaching into its buffer zone (J. Tavares in litt. 2010) may result in the loss of suitable habitat and potentially have both positive and negative influences on levels of disturbance (Olmos and Turshak 2010). The palm-oil project, however, reportedly incorporates the protection of some primary and mature secondary forest (J. Tavares in litt 2010). New road networks linking oil palm concessions may increase habitat fragmentation and disturbance (Ward-Francis et al. 2015). Road developments along the east and west coasts are increasing access to previously remote areas (A. Gascoigne in litt. 2000). Illegal logging in the south of the island has been identified as a further threat (Ward-Francis et al. 2015). Introduced Black Rat Rattus rattus, Mona Monkey Cercopithecus mona, African Civet Civettictis civetta and Weasel Mustela nivalis are all potential predators. In particular, recent reports suggest Mona Monkeys may be having a serious impact on productivity. A proposal to construct a hydroelectric dam within Obô Natural Park posed a very serious threat to key habitat for the species, this project has now ceased however future power projects remain a threat (Ward-Francis et al. 2015).
|Conservation Actions:
Conservation Actions Underway
Primary forest is protected as a zona ecologica and in the 295-km2 Obô Natural Park, although there is no law enforcement within these areas. The park was established in 1992, but was not protected by law until 2006, and although a zoning and management plan was being developed in 2008, when the first directors were appointed, the park was still lacking sufficient personnel (Olmos and Turshak 2010). A law providing for the gazetting of protected areas and the protection of threatened species has been ratified (M. Melo in litt. 2006). In 2008, a training programme with NGOs Associação de Biólogos Saotomenses (ABS) and Monte Pico was initiated to involve locals in the study and conservation of São Tomean species, and this has since been achieved (Associação dos Biólogos Santomenses in litt. 2010). Research is currently being carried out into the effects of agroforestry and the exploitation of wildlife resources on the island (del Hoyo et al. 1992, Borrow and Demey 2001). In 2013, work carried out by SPEA and funded by RSPB, mapped areas affected by oil palm plantations and surveyed for critically endangered species including Dwarf Olive Ibis (Barros 2013).
As part of the BirdLife International Preventing Extinctions programme, the Species Guardian ABS has begun training local community members in the implementation of site-based conservation; implementing an awareness raising campaign and carrying out field research and monitoring into the ecology, population status and threats to the species (BirdLife International 2008). During an international workshop held in February 2008 to promote ecotourism in São Tomé e Príncipe, birdwatching was listed as an activity that should be encouraged and Ribeira Peixe was identified as a suitable site for a pilot project (Olmos and Turshak 2010). In July 2009, ABS promoted a short course for the training of local people as bird guides at Ribeira Peixe and efforts were on-going to promote the conservation of the area (Olmos and Turshak 2010). The Government are developing an open access database to collate all biodiversity data for the island which will be used to inform land-use decisions (Ward-Francis et al. 2015). A workshop was held in January 2015, which included participants from the Government, to discuss progress towards an International Species Action Plan for the species (Ward-Francis et al. 2015).
Conservation Actions Proposed
Advocacy and awareness raising for species and primary forest protection in São Tomé. Identification of key sites and training of staff to ensure their protection. Ensure that any proposed hydroelectric dam developments are not within Obô Natural Park (Ward-Francis et al. 2015). Field research to improve knowledge on ecology, status and threats and mapping of protection zone for the species. Implement a monitoring strategy for the species. Formulate species conservation measures based on research findings and seek wider involvement in their implementation. Incorporate species conservation measures within the Obô Natural Park management plan and develop capacity for park management (Ward-Francis et al. 2015). Ensure legal protection of all remaining lowland primary forest. List it as a protected species under national law and consider establishing a captive-breeding programme. Promote access to cheaper sources of protein to reduce hunting of the species (Anon. 2011). Raise awareness of the species among the hunting community, undertake activities to encourage hunters to avoid taking the species, including through effective enforcement (Ward-Francis et al. 2015).
|BirdLife International. 2015. Bostrychia bocagei. The IUCN Red List of Threatened Species 2015: e.T22697478A79118705. . Downloaded on 26 October 2016.
|To make use of this information, please check the <Terms of Use>.
|If you see any errors or have any questions or suggestions on what is shown on this page, please provide us with feedback so that we can correct or extend the information provided


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Sean May causes a turnover.
Raymond Felton and Jackie Manuel put pressure on the ball.
Marvin Williams pulls up for two of his 20 points on the day.
Jawad Williams scores in traffic amid lots of contact.
May beats the Oakland defense down the court and scores in transition.
Rashad McCants pulls up for a three-pointer as Oakland's coach Greg Kampe looks on.


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MP3s of MPE
Fans of multi-genre, musical hybrids, pay attention -- the MPE Band is headed this way. Never heard of ´em? Well, you just might want to write that name down because the music critics familiar with the MPE Band are likin what they hear. But even so, this Philadelphia-based trio is probably too busy to notice busy with a featured spot on A&Es Random 1, criss-crossing the U.S. and Europe (including a two-week, 216-mile walking tour from Philly to D.C.). And, most important, sticking to its genre-defying songwriting.
So how does the band hear itself? Chinese fire-drill instrumentation, lush harmonies, unshakable melodies, and seat-of-your-pants spontaneity, they say, referring to their frequent instrument-sharing and musical virtuosity. MPE Bands mix of folky, jazzy, sometimes rockin' sounds brings comparisons to anything from ABBA, Zappa, Fleetwood Mac, and (yes) the Pixies. But the bands diversity and individuality can be described in one simple yet expansive word -- Americana.
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Return to SwingLifeStyle.com The Swingers Home Page
There are a total of 9626 Crestline Hts swingers, within 100 miles.
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Disclaimer: This website contains adult material. You must be over 18 to enter or 21 were applicable by law.
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Community Profile
Top 10% contributor
Given a vector x, return a vector y of the unique values in x sorted by the number of occurrences in x.
Ties are resolved by a ...
Solve this!
4 years ago
Return a list of all values (sorted smallest to largest) that appear exactly three times in the input vector x. So if
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Given the matrix A, return B in which all the rows that have one or more <http://www.mathworks.com/help/techdoc/ref/nan.html NaN...
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Who's Rising? Contest
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In the middle of a Friday night a hero's busy world of recruiting, interviews, as well as dealing with the rigors of being a high school student there is the matter of playing his senior season. Sc...
Udofia suffers injury, changes visit plans
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Sorry, this job was closed 4 years ago. See all open Consumer Marketing Specialist Jobs in Vernon, British Columbia
About Darford International
At Darford we are about our products, our people and a cause without compromise. We are a proudly Canadian nutrition company devoted to using high quality, wholesome ingredients in our food because we love all pets, not just our own. Our Team consists of people who love what they do, making a quality recipe for the pets they love, while helping abandoned animals at the same time through our Plus One Movement: ilovealldogs.org. For more information about Darford please visit www.darford.com.
Posted 4 years ago in Business, Advertising and Marketing
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It's a funny world we live in
F/S 2010 DB 3 size 9 (worn 9/10)
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I was rooting for Algieri, but now I want Khan to win just so I don't feel bad for missing out on either of those odds .
Floyd would wash the Khan Man fast...
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According to our records, Quincy Jones is possibly single.
Quincy Jones was previously married to Peggy Lipton (1974 - 1990), Ulla Andersson (1967 - 1970) and Jeri Caldwell (1957 - 1966).
He has been in relationships with Naomi Campbell (2007 - 2011), Kimberley Conrad (2005), Lisette Derouax (1999), Mickella Tupta (1998), Nastassja Kinski (1991 - 1997), Carol Reynolds (1970 - 1972) and Maryam d'Abo.
Quincy Jones has had encounters with Heba Elawadi (2006).
He is rumoured to have hooked up with Devon Wilson (1965).
Quincy Jones is a 83 year old American Musician. Born Quincy Delight Jones, Jr. on 14th March, 1933 in Chicago, Illinois, United States and educated at James A. Garfield High School, Seattle, WA (1951), he is famous for Show business legend, produced `Thriller` album, ` in a career that spans 1951–present. His zodiac sign is Pisces.
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SPEC FC - squad
DAN COHENPosition:Centre backGoals this season:2
Favourite team: Spurs
Previously joint manager of Boca Barbarians and also a member of the original Montana team of 1996/7. At 6' 4" he will head balls out of the penalty area all day long. He also has a lovely left foot which he occasionally uses to spray raking balls all over the park.