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MR, Vessel Architectural Imaging May Predict Tumor Response to Antiangiogenic Drugs

By MedImaging International staff writers
Posted on 18 Nov 2013

A combination of sophisticated imaging techniques may be able to differentiate which patients’ tumors will respond to treatment with antiangiogenic drugs and which will not.

Researchers examined patients newly diagnosed with the dangerous brain tumor glioblastoma and treated with the antiangiogenic agent cediranib. They reported that those patients for whom cediranib rapidly “normalized” abnormal blood vessels surrounding their tumors and increased blood flow within tumors survived substantially longer than did patients in whom cediranib did not increase blood flow.

The findings were published ahead of print November 4, 2013, in early edition of the journal Proceedings of the National Academy of Sciences of the United States of America (PNAS). “Two recent phase III trials of another antiangiogenic drug, bevacizumab, showed no improvement in overall survival for glioblastoma patients, but our study suggests that only a subset of such patients will really benefit from these drugs,” explained Tracy Batchelor, MD, director of the Pappas Center for Neuro-Oncology at the Massachusetts General Hospital (MGH; Boston, MA, USA; www.massgeneral.org) Cancer Center, and co-lead and corresponding author of the current study. “Our results also verify that normalization of tumor vasculature appears to be the way that antiangiogenic drugs enhance the activity of chemotherapy and radiation treatment.”

Antiangiogenic drugs, which suppress the action of factors that stimulate the growth of blood vessels, were first used for cancer treatment under the premise that they would act by “starving” tumors of their blood supply. However, since then, new evidence has suggested that the drugs’ benefits come through their capability to “normalize” the abnormal, leaky vessels that typically surround and penetrate tumors, optimizing delivery of both chemotherapy agents and the oxygen that is required for effective radiation therapy. This hypothesis was first suggested and then developed by Rakesh K. Jain, PhD, senior author of the current study and director of the Steele Laboratory for Tumor Biology in the MGH department of radiation oncology.

A 2007 clinical study led by Dr. Batchelor found evidence suggesting that cediranib, which has not yet received US Food and Drug Administration (FDA) approval, could temporarily normalize tumor vasculature in recurrent glioblastoma, but it was not clear what role normalization might have in patients’ survival. In the past few years, several research groups, with leadership from Drs. Batchelor, Jain, and other coauthors of the current study, reported evidence that cediranib alone improved blood perfusion within recurrent glioblastoma tumors in a subset of patients and improved their survival. A Nature Medicine study published earlier in 2013 used a technique called vessel architectural imaging (VAI), developed at the Martinos Center for Biomedical Imaging at MGH, to reveal that cediranib on its own improved the delivery of oxygen within tumors of some patients with recurrent glioblastoma.

VAI utilizes a temporal shift in the magnetic resonance imaging (MRI) signal, forming the basis for vessel caliber estimation, which can reveal new data on vessel type and function not evaluated by any other noninvasive imaging technique. This technology can provide new biologic clues into the treatment of patients with cancer.

Patients in the current study were participants in a clinical trial of cediranib plus radiation and chemotherapy for postsurgical treatment of newly diagnosed glioblastoma. Among the study participants in that trial, 40 also had innovative brain imaging with VAI and other MRI) techniques. Whereas all but one of the subjects in the overall trial demonstrated some evidence of vascular normalization and reduced edema (tissue swelling that can be harmful within the brain), only 20 of 40 patients were found to have persistent improvement in vessel perfusion. VAI also revealed improved oxygen delivery only in the patients with improved perfusion. Those patients survived on average nine months longer—26 months, compared with 17 months—than did those whose perfusion levels remained stable or worsened. A comparison group of glioblastoma patients treated with radiation and chemotherapy only survived an average of 14 months.

“It’s quite likely that the results we’ve found with cediranib will apply to other antiangiogenics,” Dr. Batchelor remarked. “In fact a presentation at a recent meeting showed that patients with improved perfusion from bevacizumab were also the ones in that study who lived longer. More research is needed, but these findings suggest that MR imaging techniques should play an essential role in future studies of antiangiogenic drugs in glioblastoma and possibly other types of solid tumors. We’ve received National Cancer Institute funding to study this approach with bevacizumab treatment, and we will also be investigating tumor delivery of chemotherapy and oxygen status using combined MR/PET [positron emission tomography] techniques at the Martinos Center’s MR/PET facility.”

Dr. Jain added, “We originally introduced the normalization hypothesis for antiangiogenic treatment in 2001, but it’s taken more than a decade to confirm that vascular normalization actually increases tumor perfusion and that increased perfusion, rather than tumor starvation, is what improves survival. This study provides compelling evidence that normalization-induced increased vessel perfusion is the mechanism of benefit in glioblastoma patients.”

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56 (362.87307739258): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets_archive as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.cat=10 AND dp.id=294749217 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

57 (!!!!! 1147.0317840576): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294749217 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294749217 AND published='1' LIMIT 1

58 (82.969665527344): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294749217 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294749217 AND published='1' LIMIT 1

59 (98.943710327148): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294749217 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294749217 AND published='1' LIMIT 1

60 (49.114227294922): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294749217 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294749217 AND published='1' LIMIT 1

61 (135.89859008789): select cover from jos_number where journalid in (5) and cover is not null order by left(issue,2)+right(issue,2)*12 desc limit 1

62 (501.87110900879): SELECT fid FROM jos_deeppockets WHERE id=294749217 AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE id=294749217 AND published='1' LIMIT 1

63 (288.00964355469): SELECT id,name,sponsor_text FROM jos_deeppockets dp left outer join jos_channel_sponsor cs on dp.id=cs.fid WHERE cat=10 AND TYPE='file_folder' AND published=1 AND id=212 ORDER BY `ordering`

64 (59.127807617188): select jos_twitters.link from jos_twitters where cat=10

65 (40.054321289062): select jos_facebook.link from jos_facebook where cat=10

66 (40.054321289062): select jos_google_plus.link from jos_google_plus where cat=10

67 (42.915344238281): select jos_linkedin.link from jos_linkedin where cat=10

68 (49.114227294922): SELECT fid FROM jos_deeppockets WHERE id=294749217 AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE id=294749217 AND published='1' LIMIT 1

69 (40.054321289062): SELECT id,name,sponsor_text FROM jos_deeppockets dp left outer join jos_channel_sponsor cs on dp.id=cs.fid WHERE cat=10 AND TYPE='file_folder' AND published=1 AND id=212 ORDER BY `ordering`

70 (275.1350402832): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294749217 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

71 (205.99365234375): SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294749217 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

72 (37.908554077148): SELECT id,name,title FROM jos_deeppockets WHERE cat=10 AND TYPE='file_folder' AND published=1 AND id != 294743300 AND id != 294743301 AND id != 294743302 AND id != 294743303 AND id != 294743304 AND id != 294743305 AND id != 294743306 AND id != 294743307 AND id != 294743308 AND id != 294743309 AND id != 294743310 AND metakey != 'aacc' ORDER BY `ordering`

73 (56.982040405273): SELECT show_live FROM jos_com_show_setting LIMIT 1

74 (32.901763916016): SELECT show_live FROM jos_com_show_setting LIMIT 1

75 (30.040740966797): SELECT show_live FROM jos_com_show_setting LIMIT 1

76 (31.948089599609): SELECT show_live FROM jos_com_show_setting LIMIT 1

77 (30.040740966797): SELECT show_live FROM jos_com_show_setting LIMIT 1

78 (30.994415283203): SELECT show_live FROM jos_com_show_setting LIMIT 1

79 (28.848648071289): SELECT show_live FROM jos_com_show_setting LIMIT 1

80 (30.040740966797): SELECT show_live FROM jos_com_show_setting LIMIT 1

81 (32.901763916016): SELECT show_live FROM jos_com_show_setting LIMIT 1

82 (40.054321289062): SELECT show_live FROM jos_com_show_setting LIMIT 1

83 (31.948089599609): SELECT show_live FROM jos_com_show_setting LIMIT 1

84 (36.001205444336): SELECT show_live FROM jos_com_show_setting LIMIT 1

85 (36.954879760742): SELECT show_live FROM jos_com_show_setting LIMIT 1

86 (30.994415283203): SELECT show_live FROM jos_com_show_setting LIMIT 1

87 (52.928924560547): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294749217 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

88 (31.948089599609): SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294749217 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

89 (36.954879760742): SELECT id,name,title FROM jos_deeppockets WHERE cat=10 AND TYPE='file_folder' AND published=1 AND id != 294743300 AND id != 294743301 AND id != 294743302 AND id != 294743303 AND id != 294743304 AND id != 294743305 AND id != 294743306 AND id != 294743307 AND id != 294743308 AND id != 294743309 AND id != 294743310 AND metakey != 'aacc' ORDER BY `ordering`

90 (75.817108154297): SELECT show_live FROM jos_com_show_setting LIMIT 1

91 (41.007995605469): SELECT show_live FROM jos_com_show_setting LIMIT 1

92 (46.968460083008): SELECT show_live FROM jos_com_show_setting LIMIT 1

93 (39.100646972656): SELECT show_live FROM jos_com_show_setting LIMIT 1

94 (36.001205444336): SELECT show_live FROM jos_com_show_setting LIMIT 1

95 (29.087066650391): SELECT show_live FROM jos_com_show_setting LIMIT 1

96 (26.941299438477): SELECT show_live FROM jos_com_show_setting LIMIT 1

97 (27.894973754883): SELECT show_live FROM jos_com_show_setting LIMIT 1

98 (26.941299438477): SELECT show_live FROM jos_com_show_setting LIMIT 1

99 (28.133392333984): SELECT show_live FROM jos_com_show_setting LIMIT 1

100 (29.087066650391): SELECT show_live FROM jos_com_show_setting LIMIT 1

101 (27.894973754883): SELECT show_live FROM jos_com_show_setting LIMIT 1

102 (33.855438232422): SELECT show_live FROM jos_com_show_setting LIMIT 1

103 (35.04753112793): SELECT show_live FROM jos_com_show_setting LIMIT 1

104 (116.10984802246): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294749217 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294749217 AND published='1' LIMIT 1

105 (58.889389038086): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294749217 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294749217 AND published='1' LIMIT 1

106 (56.028366088867): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.cat=10 AND dp.id=294749217 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

107 (49.829483032227): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets_archive as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.cat=10 AND dp.id=294749217 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

108 (70.095062255859): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294749217 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294749217 AND published='1' LIMIT 1

109 (43.869018554688): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294749217 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294749217 AND published='1' LIMIT 1

110 (63.896179199219): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.id=294749217 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

111 (477.07557678223): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets_archive as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.id=294749217 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

112 (614.88151550293): SELECT dp.name, dp.id, dp2.name as channel, ex.name as author_name, ex.specialization, ex.images FROM jos_deeppockets as dp LEFT JOIN jos_experts as ex ON ex.id = dp.author LEFT JOIN jos_deeppockets as dp2 ON dp2.id = dp.fid WHERE dp.author != 0 AND dp.cat = 10 AND dp.published = 1 AND ( (dp.fid = 294743300) OR (dp.fid = 294743301) OR (dp.fid = 294743302) OR (dp.fid = 294743303) OR (dp.fid = 294743304) OR (dp.fid = 294743305) OR (dp.fid = 294743306) OR (dp.fid = 294743307) OR (dp.fid = 294743308) OR (dp.fid = 294743309) OR (dp.fid = 294743310) ) ORDER BY RAND() LIMIT 1

113 (375.03242492676): SELECT dp.name, dp.id, dp2.name as channel, ex.name as author_name, ex.specialization, ex.images FROM jos_deeppockets as dp LEFT JOIN jos_experts as ex ON ex.id = dp.author LEFT JOIN jos_deeppockets as dp2 ON dp2.id = dp.fid WHERE dp.author != 0 AND dp.cat = 10 AND dp.published = 1 AND ( (dp.fid = 294743300) OR (dp.fid = 294743301) OR (dp.fid = 294743302) OR (dp.fid = 294743303) OR (dp.fid = 294743304) OR (dp.fid = 294743305) OR (dp.fid = 294743306) OR (dp.fid = 294743307) OR (dp.fid = 294743308) OR (dp.fid = 294743309) OR (dp.fid = 294743310) ) ORDER BY RAND() LIMIT 1

114 (73.909759521484): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294749217 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294749217 AND published='1' LIMIT 1

115 (46.014785766602): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294749217 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294749217 AND published='1' LIMIT 1

116 (72.002410888672): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294749217 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294749217 AND published='1' LIMIT 1

117 (51.975250244141): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294749217 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294749217 AND published='1' LIMIT 1

118 (91.791152954102): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294749217 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294749217 AND published='1' LIMIT 1

119 (44.107437133789): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294749217 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294749217 AND published='1' LIMIT 1

120 (42.915344238281): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294749217 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294749217 AND published='1' LIMIT 1

121 (37.908554077148): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294749217 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294749217 AND published='1' LIMIT 1

122 (363.11149597168): SELECT * FROM trending_articles WHERE `journal_id` = 10 AND `timestamp` <= NOW() + INTERVAL 7 DAY ORDER BY `order`

123 (!!!!! 20002.126693726): SELECT * FROM jos_deeppockets WHERE jos_deeppockets.cat = 10 AND jos_deeppockets.type = 'deeppockets_item' AND jos_deeppockets.published = 1 AND jos_deeppockets.created + INTERVAL 14 DAY >= NOW() ORDER BY jos_deeppockets.hits DESC LIMIT 7

124 (485.89706420898): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294749217 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294749217 AND type='deeppockets_item' AND published='1' LIMIT 1

125 (!!!!! 7498.025894165): ( SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.video != '' AND dp.video_source != '' AND dp.cat = 10 AND dp.published = 1 AND dp.type != 'deeppockets_item_link' ORDER BY created DESC LIMIT 3 ) UNION ( SELECT dpa.id, dpa.name, dpa.title, dpa.video, dpa.video_source, dpa.created FROM jos_deeppockets_archive AS dpa WHERE dpa.video != '' AND dpa.video_source != '' AND dpa.cat = 10 AND dpa.published = 1 AND dpa.type != 'deeppockets_item_link' ORDER BY created DESC LIMIT 3 ) ORDER BY created DESC LIMIT 3

126 (72.956085205078): ( SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.video != '' AND dp.video_source != '' AND dp.cat = 10 AND dp.published = 1 AND dp.type != 'deeppockets_item_link' ORDER BY created DESC LIMIT 3 ) UNION ( SELECT dpa.id, dpa.name, dpa.title, dpa.video, dpa.video_source, dpa.created FROM jos_deeppockets_archive AS dpa WHERE dpa.video != '' AND dpa.video_source != '' AND dpa.cat = 10 AND dpa.published = 1 AND dpa.type != 'deeppockets_item_link' ORDER BY created DESC LIMIT 3 ) ORDER BY created DESC LIMIT 3

127 (338.79280090332): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294803337 LIMIT 1

128 (46.968460083008): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294803337 LIMIT 1

129 (211.95411682129): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294803276 LIMIT 1

130 (34.093856811523): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294803276 LIMIT 1

131 (180.95970153809): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets_archive AS dp WHERE dp.id = 294803276 LIMIT 1

132 (31.948089599609): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets_archive AS dp WHERE dp.id = 294803276 LIMIT 1

133 (178.09867858887): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294802958 LIMIT 1

134 (56.028366088867): SELECT dp.id, dp.name, dp.title, dp.video, dp.video_source, dp.created FROM jos_deeppockets AS dp WHERE dp.id = 294802958 LIMIT 1

135 (486.13548278809): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294749217 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

136 (349.99847412109): SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294749217 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

137 (311.13624572754): SELECT name FROM jos_deeppockets WHERE id=212

138 (50.067901611328): SELECT name FROM jos_deeppockets WHERE id=212

139 (656.1279296875): SELECT *, DATE_FORMAT(publish_up,'%d %b %Y') AS date_publish_up, DATE_FORMAT(publish_down,'%d %b %Y') AS date_publish_down FROM jos_events WHERE state=1 AND publish_up > NOW() and extra_info REGEXP '((;)|(^))212((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3

140 (556.94580078125): SELECT *, DATE_FORMAT(publish_up,'%d %b %Y') AS date_publish_up, DATE_FORMAT(publish_down,'%d %b %Y') AS date_publish_down FROM jos_events WHERE state=1 AND publish_up > NOW() and extra_info REGEXP '((;)|(^))212((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3

141 (75.101852416992): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294749217 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294749217 AND published='1' LIMIT 1

142 (52.928924560547): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294749217 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294749217 AND published='1' LIMIT 1

143 (!!!!! 8251.9054412842): TRUNCATE TABLE jos_trademed_module

144 (94.890594482422): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.cat=10 AND dp.id=294749217 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

145 (57.93571472168): SELECT dp.*, ch.title as channel, exp.name as author_name, exp.specialization as author_specialization, exp.images as author_photo FROM jos_deeppockets_archive as dp LEFT JOIN jos_experts as exp ON exp.id = dp.author LEFT JOIN jos_deeppockets as ch ON dp.fid = ch.id WHERE 1=1 AND dp.cat=10 AND dp.id=294749217 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1

146 (942.94548034668): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294749217 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

147 (57.220458984375): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294749217 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1

148 (102.99682617188): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294749217 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294749217 AND published='1' LIMIT 1

149 (75.101852416992): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294749217 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294749217 AND published='1' LIMIT 1

150 (!!!!! 1318.9315795898): SELECT jos_item.* FROM jos_item INNER JOIN jos_number ON jos_item.numberID=jos_number.id WHERE 1=1 AND (jos_item.imgMini<>'') AND jos_item.type='L' AND jos_item.numberID= ( SELECT jos_number.id FROM jos_number WHERE jos_number.journalID IN (10) and jos_number.id in (select distinct jos_number.id from jos_number join jos_item on jos_item.numberid=jos_number.id where jos_item.type='P') ORDER BY (CONVERT(SUBSTRING(issue,1,2),SIGNED) + (CONVERT(SUBSTRING(issue,3,2),SIGNED)*100)) DESC LIMIT 0,1 ) ORDER BY RAND() DESC LIMIT 6

151 (73.19450378418): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294749217 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294749217 AND published='1' LIMIT 1

152 (56.028366088867): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294749217 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294749217 AND published='1' LIMIT 1

153 (42.200088500977): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294749217 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294749217 AND type='deeppockets_item' AND published='1' LIMIT 1

154 (34.093856811523): select distinct links.* from jos_textlinks links join jos_textlinks_placement placement on links.id=placement.link_id where journal_id=(10) and (channel_id=212 or channel_id is null)

155 (51.021575927734): select distinct links.* from jos_textlinks links join jos_textlinks_placement placement on links.id=placement.link_id where journal_id=(10) and (channel_id=212 or channel_id is null)

156 (41.007995605469): SELECT livesite FROM jos_dp_categories WHERE id=10 AND published='1' LIMIT 1

157 (157.11784362793): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294749217 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294749217 AND published='1' LIMIT 1

158 (68.187713623047): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294749217 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294749217 AND published='1' LIMIT 1

159 (108.95729064941): select jos_twitters.link from jos_twitters where cat=10

160 (28.848648071289): select jos_facebook.link from jos_facebook where cat=10

161 (27.894973754883): select jos_google_plus.link from jos_google_plus where cat=10

162 (25.98762512207): select jos_linkedin.link from jos_linkedin where cat=10

163 (263.92936706543): update jos_bannersmanager_banner set impmade=impmade+1 where id in(14615,14202,14203)

164 (!!!!! 2060.1749420166): insert into jos_banners_delta values (14615,'2025-06-25 00:28:27','216.73.216.120','view'),(14202,'2025-06-25 00:28:27','216.73.216.120','view'),(14203,'2025-06-25 00:28:27','216.73.216.120','view')

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