Lorem Sit Amet Dolor
123 abc lane, Townsville, ZZ 00000, USA
Funding Progress: $§ / $§§§§§
Diffuse Intrinsic Pontine Glioma.
ClinicalDIPG, Childhood (Brain Cancer)
Lay Summary
In tumors like DIPG, the diagnosis itself spells a death sentence for the child affected. For several decades, none of the altered fractionation radiotherapy or additional chemotherapy or targeted agents have shown a significant benefit over conventional radiotherapy. We propose amalgamation of several known and tested hypothesis in DIPG or other similar difficult disease conditions with almost nill possible harm to these patients but hope to improve their outcomes.
We propose to do an MRI perfusion in addition to usual MRI at diagnosis and stratify them into hyperperfused or hypoperfused based on the criteria from our previously published experience in DIPG. The hyperperfused patients will receive additional low dose BVZ weekly with conventional standard radiotherapy. It is hypothesized that low dose BVZ will decrease hypoxia and improve the efficacy of conventional radiotherapy and in turn improve outcomes. Conventional BVZ doses with radiotherapy have been extensively tested in DIPG and are well tolerated.
The hypo-perfused patients will receive ultra-low dose radiotherapy fractionation equivalent to conventional RT biological dose. As it is assumed that hypoperfused tumors are radioresistant, we hypothesis that the ultra-low dose radiotherapy may overcome that radioresistance as seen in adult GBM patients and may improve outcomes. It may be of little inconvenience to the patients as they will need to stay in hospital campus for longer times but if this approach improves outcomes, we believe this inconvenience would be acceptable. The logistic burden in hospital system should not be significant as we plan to accrue only 20 patients over 1-2 years, which would mean probably one patient a month would be on treatment at any time.
Reviewing previously published literature, it does not suggest that this protocol would put the patients at any additional significant risk of harm as compared to their imminent fate otherwise.
Executive Summary
Scientific Merit & Feasibility
In tumors like DIPG, the diagnosis itself spells a death sentence for the child affected. For several decades, none of the altered fractionation radiotherapy or additional chemotherapy or targeted agents have shown a significant benefit over conventional radiotherapy. We propose amalgamation of several known and tested hypothesis in DIPG or other similar difficult disease conditions with almost nill possible harm to these patients but hope to improve their outcomes.
We propose to do an MRI perfusion in addition to usual MRI at diagnosis and stratify them into hyperperfused or hypoperfused based on the criteria from our previously published experience in DIPG. The hyperperfused patients will receive additional low dose BVZ weekly with conventional standard radiotherapy. It is hypothesized that low dose BVZ will decrease hypoxia and improve the efficacy of conventional radiotherapy and in turn improve outcomes. Conventional BVZ doses with radiotherapy have been extensively tested in DIPG and are well tolerated.
The hypo-perfused patients will receive ultra-low dose radiotherapy fractionation equivalent to conventional RT biological dose. As it is assumed that hypoperfused tumors are radioresistant, we hypothesis that the ultra-low dose radiotherapy may overcome that radioresistance as seen in adult GBM patients and may improve outcomes. It may be of little inconvenience to the patients as they will need to stay in hospital campus for longer times but if this approach improves outcomes, we believe this inconvenience would be acceptable. The logistic burden in hospital system should not be significant as we plan to accrue only 20 patients over 1-2 years, which would mean probably one patient a month would be on treatment at any time.
Reviewing previously published literature, it does not suggest that this protocol would put the patients at any additional significant risk of harm as compared to their imminent fate otherwise.
Expertise
We are the largest center multidisciplinary comprehensive cancer care center in South Asia. We see about 30-50 DIPG patients each year with a fully developed neuro-oncology disease management group, which internationally recognized for its academic and research contributions. Previously we have published one clinical phase II study of radiotherapy with temozolomide in DIPG which is widely quoted in literature. Other than this we have conducted and published several other studies in other brain tumors.
Description of Research Proposal
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Class aptent taciti sociosqu ad litora torquent per conubia nostra, per inceptos himenaeos. Donec faucibus, turpis sit amet maximus dapibus, sapien nisl bibendum turpis, pharetra commodo tellus libero vel nulla. Sed nec velit viverra, congue sapien et, gravida libero. Proin eget ante eget turpis egestas accumsan. Aliquam arcu nibh, aliquam rhoncus vulputate in, pellentesque at sem. Maecenas cursus tempus nibh id tempus. Mauris dolor sapien, lacinia sit amet condimentum at, dapibus eget lectus. Phasellus vel pellentesque ex. Nunc aliquam in ligula at tristique. In mollis suscipit felis eu finibus. Nullam non dignissim nibh, nec suscipit ex. Suspendisse tincidunt et mauris id finibus. Aliquam vehicula a sem quis venenatis.
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Sed at tortor et tortor tincidunt feugiat id in dui. Vivamus eget justo nisl. Aenean congue laoreet nisl a elementum. Nunc consectetur velit non ligula sollicitudin, quis eleifend urna sollicitudin. Sed tincidunt, nisl quis varius venenatis, dui massa condimentum tellus, sed sollicitudin diam magna mollis augue. Sed venenatis commodo purus id malesuada. Aenean volutpat elit vel gravida consectetur. Vestibulum diam quam, lacinia ac tortor eget, tincidunt dapibus dui. Pellentesque habitant morbi tristique senectus et netus et malesuada fames ac turpis egestas. Proin nisl leo, pretium sed arcu imperdiet, hendrerit sollicitudin sem. Duis non magna at nunc sagittis ullamcorper a id est. Maecenas cursus nisl in faucibus hendrerit.
Sed hendrerit vitae purus et tempor. Aenean vitae varius velit. Nullam aliquet ipsum elit. Mauris vestibulum purus et metus imperdiet, quis gravida eros pretium. Curabitur rutrum nunc vitae tincidunt condimentum. Aenean sit amet augue velit. Nunc tristique quis lorem id pharetra. Pellentesque sollicitudin, eros sed egestas rutrum, nulla nisl sodales elit, ut imperdiet nunc lectus sit amet nulla. Ut malesuada finibus libero. Curabitur mi dolor, sollicitudin quis bibendum quis, dictum sed enim.
Pellentesque nibh erat, egestas sit amet sagittis malesuada, rhoncus at neque. Mauris maximus commodo tortor, non egestas magna finibus vitae. Sed hendrerit nulla vel venenatis tempor. Suspendisse tristique tincidunt libero et placerat. Nam tincidunt condimentum lorem, vel pharetra est iaculis sed. Nullam ac tincidunt orci. Quisque pharetra ut sem sit amet aliquam. Phasellus risus libero, varius in condimentum vel, commodo id ipsum. Aliquam in metus cursus, mattis diam ut, aliquam magna. Suspendisse facilisis dui et orci varius, suscipit facilisis augue dapibus. In eget nibh ipsum. Suspendisse eget pharetra est, quis condimentum felis. Fusce scelerisque congue libero, sed aliquam mi elementum a. Etiam scelerisque ante non auctor porta. Nam eu nunc id ex finibus dictum. Praesent dui ex, dictum ac massa eget, rutrum gravida nisi.
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Budget
Lorem ipsum dolor sit amet, consectetur adipiscing elit. Integer gravida non felis non euismod. Fusce finibus aliquet consequat. Nam ac metus bibendum, iaculis purus sed, suscipit ligula. Proin et nisi libero. Mauris non urna urna. Nullam augue eros, fringilla sed mauris vitae, porta tincidunt risus. Aliquam sed tincidunt sem. Quisque lacinia quam tortor, imperdiet efficitur odio iaculis in. Sed ultricies condimentum volutpat. Vivamus dignissim faucibus porta.
Curabitur ut ipsum non odio malesuada vulputate. Morbi maximus, est eu lobortis molestie, tortor sapien hendrerit nisi, in cursus odio diam ut odio. Fusce pulvinar volutpat velit. Aliquam erat volutpat. Integer rhoncus mollis suscipit. Praesent non ipsum mollis, finibus nunc a, scelerisque nibh. In feugiat iaculis velit, eu semper lacus dignissim nec. Praesent vitae nisi leo. Cras venenatis dictum magna ut semper. Sed eget eros nibh. Sed vitae quam sed dolor faucibus elementum. Curabitur interdum porttitor finibus. Nullam tincidunt odio lectus, sit amet rhoncus libero dapibus sed. Sed mollis egestas enim, vel porta tortor volutpat eget.
Morbi orci urna, ornare non pretium eget, pulvinar eget magna. Ut consectetur efficitur varius. Fusce ac aliquet mauris, at mattis ligula. Quisque est libero, interdum id orci et, ornare luctus diam. Proin commodo lectus id accumsan blandit. Nulla eu turpis interdum, luctus ante ac, imperdiet tellus. In semper enim eu tristique aliquam.
Collaborations and Conflicts of Interest
Lorem ipsum dolor sit amet, consectetur adipiscing elit. Integer gravida non felis non euismod. Fusce finibus aliquet consequat. Nam ac metus bibendum, iaculis purus sed, suscipit ligula. Proin et nisi libero. Mauris non urna urna. Nullam augue eros, fringilla sed mauris vitae, porta tincidunt risus. Aliquam sed tincidunt sem. Quisque lacinia quam tortor, imperdiet efficitur odio iaculis in. Sed ultricies condimentum volutpat. Vivamus dignissim faucibus porta.
Curabitur ut ipsum non odio malesuada vulputate. Morbi maximus, est eu lobortis molestie, tortor sapien hendrerit nisi, in cursus odio diam ut odio. Fusce pulvinar volutpat velit. Aliquam erat volutpat. Integer rhoncus mollis suscipit. Praesent non ipsum mollis, finibus nunc a, scelerisque nibh. In feugiat iaculis velit, eu semper lacus dignissim nec. Praesent vitae nisi leo. Cras venenatis dictum magna ut semper. Sed eget eros nibh. Sed vitae quam sed dolor faucibus elementum. Curabitur interdum porttitor finibus. Nullam tincidunt odio lectus, sit amet rhoncus libero dapibus sed. Sed mollis egestas enim, vel porta tortor volutpat eget.