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Radiotherapy Targets Resistant Pockets in Metastatic Lung Cancer

By MedImaging International staff writers
Posted on 09 Jan 2013
New research revealed that when pockets of resistant cancer develop, it is frequently possible to target these resistant areas with focused, targeted radiation while continuing administering the cancer agents to retain control of the majority of the disease that continues to depend on the primary mutation.

The key ability of cancer is remarkable in its ability to mutate; once it has initiated the process it learns to mutate continuously. This means that different tumors within a single patient or even different areas within the same cancerous deposit may develop different genetic traits. This heterogeneity helps cancer escape control by new, targeted cancer therapy drugs. Two of these targeted cancer drugs, crizotinib and erlotinib, are extremely advantageous for patients whose cancers depend on the basic mutations that the drugs exploit. That is, until pockets of the cancer mutate again, turning their dependence away from the original, targeted mutation. Due to continuing mutation, the unfortunate truth is that while crizotinib and erlotinib extend patients’ lives, the drugs eventually, inevitably, inexorably stop working.

The researchers, from the University of Colorado (UC) Cancer Center (Denver, USA) published their study’s findings in the December 2012 issue of the International Association for the Study of Lung Cancer’s (IASLC) Journal of Thoracic Oncology. “We liken this to weeding the garden,” said Andrew Weickhardt, MD, senior clinical fellow at the CU Cancer Center. “In nearly half of patients, when these drugs stop working, they stop working only in a limited number of sites. Given how well these people tolerate the medication, it made sense to us to treat these isolated spots with radiation [or in one case, surgery], and continue the same drug, which was obviously working elsewhere.”

This study of 65 patients showed that continuing either crizotinib or erlotinib after the treatment of resistant pockets was associated with more than half a year of additional cancer control. The benefit was especially robust when the metastatic lung cancer progressed in the brain. The brain is unfortunately a common site of progression because the molecules of crizotinib and erlotinib have difficulty in passing from the bloodstream into the brain, across the so-called blood-brain barrier. Cancer cells position themselves elusively in the brain, hidden away from the drugs.

“We expect using radiation to zap these pockets of cancer in the brain, and then continuing the targeted therapy to become the standard of care,” said CU Cancer Center investigator, Ross Camidge, MD, PhD, director of the thoracic oncology clinical program at University of Colorado Hospital.

There was also a smaller but still significant progression-free survival advantage for using this application in patients whose cancers progressed originally outside the brain. If and when pockets of crizotinib- or erlotinib-resistant lung cancer are detected, “Clinicians should consider using radiation in the body and especially in the brain to weed the garden while continuing the drug, when there is good ongoing control of the cancer in other sites in the body,” Dr. Weickhardt said.

Related Links:
University of Colorado Cancer Center


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92 (28.133392333984): SELECT show_live FROM jos_com_show_setting LIMIT 1
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94 (35.04753112793): SELECT show_live FROM jos_com_show_setting LIMIT 1
95 (33.140182495117): SELECT show_live FROM jos_com_show_setting LIMIT 1
96 (30.994415283203): SELECT show_live FROM jos_com_show_setting LIMIT 1
97 (73.909759521484): SELECT show_live FROM jos_com_show_setting LIMIT 1
98 (41.007995605469): SELECT show_live FROM jos_com_show_setting LIMIT 1
99 (30.994415283203): SELECT show_live FROM jos_com_show_setting LIMIT 1
100 (27.894973754883): SELECT show_live FROM jos_com_show_setting LIMIT 1
101 (28.133392333984): SELECT show_live FROM jos_com_show_setting LIMIT 1
102 (28.133392333984): SELECT show_live FROM jos_com_show_setting LIMIT 1
103 (28.133392333984): SELECT show_live FROM jos_com_show_setting LIMIT 1
104 (68.902969360352): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294744156 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294744156 AND published='1' LIMIT 1
105 (43.869018554688): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294744156 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294744156 AND published='1' LIMIT 1
106 (50.067901611328): 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=294744156 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
107 (464.20097351074): 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=294744156 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
108 (!!!!! 3531.2175750732): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294744156 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294744156 AND published='1' LIMIT 1
109 (!!!!! 3979.9213409424): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294744156 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294744156 AND published='1' LIMIT 1
110 (56.982040405273): 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=294744156 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
111 (665.90309143066): 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=294744156 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
112 (689.98336791992): 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 (421.04721069336): 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 (83.92333984375): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294744156 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294744156 AND published='1' LIMIT 1
115 (58.889389038086): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294744156 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294744156 AND published='1' LIMIT 1
116 (51.021575927734): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294744156 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294744156 AND published='1' LIMIT 1
117 (38.862228393555): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294744156 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294744156 AND published='1' LIMIT 1
118 (163.07830810547): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294744156 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294744156 AND published='1' LIMIT 1
119 (49.114227294922): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294744156 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294744156 AND published='1' LIMIT 1
120 (48.160552978516): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294744156 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294744156 AND published='1' LIMIT 1
121 (39.815902709961): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294744156 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294744156 AND published='1' LIMIT 1
122 (345.94535827637): SELECT * FROM trending_articles WHERE `journal_id` = 10 AND `timestamp` <= NOW() + INTERVAL 7 DAY ORDER BY `order`
123 (!!!!! 47358.989715576): 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 (645.16067504883): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294744156 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294744156 AND type='deeppockets_item' AND published='1' LIMIT 1
125 (!!!!! 21960.973739624): ( 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 (99.897384643555): ( 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 (475.16822814941): 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 (230.78918457031): 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 (786.78131103516): 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 (473.0224609375): 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 (404.83474731445): 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 (!!!!! 1844.1677093506): 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 (420.09353637695): 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 (52.928924560547): 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 (763.89312744141): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294744156 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
136 (355.00526428223): SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294744156 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
137 (180.95970153809): SELECT name FROM jos_deeppockets WHERE id=211
138 (33.855438232422): SELECT name FROM jos_deeppockets WHERE id=211
139 (636.81602478027): 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 '((;)|(^))211((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3
140 (586.98654174805): SELECT *, DATE_FORMAT(publish_up,'%d %b %Y') AS date_publish_up, DATE_FORMAT(publish_down,'%d %b %Y') AS date_publish_down FROM jos_events WHERE state=1 AND publish_up > NOW() and extra_info REGEXP '((;)|(^))211((;)|($))' AND catid IN (0,110) ORDER BY publish_up ASC LIMIT 3
141 (410.07995605469): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294744156 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294744156 AND published='1' LIMIT 1
142 (!!!!! 6181.001663208): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294744156 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294744156 AND published='1' LIMIT 1
143 (!!!!! 16374.826431274): TRUNCATE TABLE jos_trademed_module
144 (!!!!! 5468.8453674316): 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=294744156 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
145 (705.95741271973): 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=294744156 AND (dp.type='deeppockets_item' OR dp.type='deeppockets_item_link') AND dp.published='1' LIMIT 1
146 (722.88513183594): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294744156 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
147 (!!!!! 2872.9438781738): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294744156 AND (type='deeppockets_item' OR type='deeppockets_item_link') AND published='1' LIMIT 1
148 (148.05793762207): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294744156 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294744156 AND published='1' LIMIT 1
149 (52.928924560547): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294744156 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294744156 AND published='1' LIMIT 1
150 (!!!!! 1281.0230255127): 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 (69.856643676758): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294744156 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294744156 AND published='1' LIMIT 1
152 (60.081481933594): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294744156 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294744156 AND published='1' LIMIT 1
153 (577.92663574219): SELECT fid FROM jos_deeppockets WHERE cat=10 AND id=294744156 AND type='deeppockets_item' AND published='1' union SELECT fid FROM jos_deeppockets_archive WHERE cat=10 AND id=294744156 AND type='deeppockets_item' AND published='1' LIMIT 1
154 (97.990036010742): 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=211 or channel_id is null)
155 (50.067901611328): 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=211 or channel_id is null)
156 (35.04753112793): SELECT livesite FROM jos_dp_categories WHERE id=10 AND published='1' LIMIT 1
157 (788.92707824707): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294744156 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294744156 AND published='1' LIMIT 1
158 (75.817108154297): SELECT * FROM jos_deeppockets WHERE 1=1 AND id=294744156 AND published='1' union SELECT * FROM jos_deeppockets_archive WHERE 1=1 AND id=294744156 AND published='1' LIMIT 1
159 (!!!!! 1031.8756103516): select jos_twitters.link from jos_twitters where cat=10
160 (331.87866210938): select jos_facebook.link from jos_facebook where cat=10
161 (39.100646972656): select jos_google_plus.link from jos_google_plus where cat=10
162 (30.994415283203): select jos_linkedin.link from jos_linkedin where cat=10