{"id":23,"date":"2018-10-17T16:17:53","date_gmt":"2018-10-17T16:17:53","guid":{"rendered":"https:\/\/lab.research.sickkids.ca\/ramaswamy\/?page_id=23"},"modified":"2018-11-09T14:52:17","modified_gmt":"2018-11-09T14:52:17","slug":"timeline","status":"publish","type":"page","link":"https:\/\/lab.research.sickkids.ca\/ramaswamy\/timeline\/","title":{"rendered":"timeline"},"content":{"rendered":"

[vc_row type=”1″ animation=”fadeIn” margin_top=”-50px”][vc_column][vc_empty_space height=”150px”][\/vc_column][\/vc_row][vc_row type=”1″ animation=”fadeIn” bg_repeat=”repeat” bg_cover=”true” bg_attachment=”true”][vc_column width=”1\/6″][\/vc_column][vc_column width=”2\/3″ animation=”fadeIn”][vc_column_text css_animation=”fadeIn”]<\/p>\n

History of Medulloblastoma Research<\/h3>\n

(Adapted from Brain Tumour Magazine with permission. Contents researched by SickKids physicians Dr. Vijay Ramaswamy and Dr. Eric Bouffet.<\/em>)<\/p>\n

 <\/p>\n

EACH year medulloblastoma affects five\u00a0children in every one million,\u00a0one of\u00a0the most common malignant brain tumours\u00a0in children.<\/p>\n

This timeline illustrates the most important\u00a0breakthroughs and advances in the knowledge\u00a0and management of medulloblastoma and highlights the remarkable progress clinicians and researchers have made over the years.<\/p>\n

With recent advances in molecular and\u00a0genomic technologies, the landscape of\u00a0medulloblastoma is changing.\u00a0We can expect the treatment\u00a0of this disease to see further\u00a0important changes in the\u00a0next decades.[\/vc_column_text][vc_empty_space]

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2017<\/strong><\/h4>\n

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Using integrated genomics, multiple global studies show that medulloblastoma is actually comprised of 12 distinct molecular subtypes, including two key clinically relevant infant medulloblastoma groups.<\/p>\n

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2016<\/strong><\/h4>\n

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International team of researchers discovers previously ascribed clinical risk factors associated with surgery are far less important than previously throught once accounting for molecular subgroup.<\/p>\n

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2015<\/strong><\/h4>\n

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Global consensus statement redefines risk stratification of medulloblastoma (Ramaswamy et al, Acta Neuropathological, 2016<\/a>).<\/p>\n

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2014<\/strong><\/h4>\n

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Several multi-centre studies in North America and Europe initiated evaluating de-escalation therapies for WNT Medulloblastoma due to the excellent prognosis in this sub-group offering the possibility that this subset of patients could be cured with less neurocognitive and neuroendocrine sequelae.<\/p>\n

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2013<\/strong><\/h4>\n

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A study of recurrent medulloblastoma reveals that subgroup\u00a0affiliation is stable at recurrence, and that Group 3 and 4\u00a0medulloblastoma frequently recur in the metastatic compartment. This\u00a0suggests that progress in improving outcomes for these two subgroups\u00a0must focus on treatment of the metastatic compartment.<\/p>\n

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2012<\/strong><\/h4>\n

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  1. Results of the SIOP-PNET4 randomized study that\u00a0assessed the role of hyperfractionated craniospinal\u00a0radiation (HFRT). In this trial, HFRT was not superior to\u00a0standard radiation, which therefore remains standard\u00a0of care in medulloblastoma.<\/li>\n
  2. A cross-species genomic study reveals that in\u00a0disseminated medulloblastoma, the metastatic\u00a0compartment is distinct from the primary tumour in both\u00a0human and mouse medulloblastoma.<\/li>\n<\/ol>\n

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    2011<\/strong><\/h4>\n

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    Multiple genomic and next-generation sequencing studies\u00a0reveal that medulloblastoma is a heterogeneous tumour comprising of at least four distinct molecular variants (WNT, SHH, Group 3,\u00a0Group 4).<\/p>\n<\/q><\/p>\n

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    2009<\/strong><\/h4>\n

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    Single case report of an adult treated with the smoothened\u00a0inhibitor GDC-0449 reveals a dramatic but transient response, leading\u00a0to several clinical trials of smoothened inhibition.<\/p>\n

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    2006<\/strong><\/h4>\n

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    Genomic analysis of\u00a0medulloblastoma reveals multiple molecular subgroups of\u00a0medulloblastoma. This is the first study\u00a0to suggest the existence of distinct molecular variants\u00a0of medulloblastoma.<\/p>\n<\/q><\/p>\n

    Multicentre studies initiated by the Children\u2019s Cancer\u00a0Group (CCG9961) and St. Jude\u2019s (SJMB96) of reduced dose\u00a0craniospinal irradiation followed by cisplatin-based adjuvant\u00a0chemotherapy for average risk medulloblastoma patients\u00a0showed five-year survivals of over 80%.<\/div><\/div> <\/div><\/div>

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    2005<\/strong><\/h4>\n

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    1. Nuclear beta-catenin identified\u00a0as a marker of excellent prognosis\u00a0in medulloblastoma, and is later shown\u00a0to be a defining feature of the Wingless\u00a0(WNT) subgroup of medulloblastoma.<\/li>\n
    2. A German study reveals\u00a0that a high proportion of infants with\u00a0desmoplastic histology can be successfully\u00a0treated with chemotherapy only.<\/li>\n<\/ol>\n

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      2002<\/strong><\/h4>\n

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      First whole genomic analysis of embryonal\u00a0tumours published by Pomeroy et al in Nature\u00a0showing that medulloblastoma is distinct from other\u00a0embryonal tumours of the central nervous system,\u00a0in particular atypical\/teratoid rhabdoid tumours and\u00a0CNS-PNET. This study also showed that classic\u00a0histology medulloblastoma has distinct profiles from\u00a0desmoplastic histology.<\/p>\n

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      1999<\/strong><\/h4>\n

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      Results of CCG9892, a pilot study that shows\u00a0an excellent five-year survival rate in children with\u00a0average risk medulloblastoma treated with reduced\u00a0dose radiation and chemotherapy combining\u00a0cisplatin\/CCNU\/vincristine.<\/p>\n

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      1997<\/strong><\/h4>\n

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      First evidence that deletion of the Patched1\u00a0gene is responsible for medulloblastoma formation\u00a0in mice. This represents the first transgenic model\u00a0of medulloblastoma.<\/p>\n<\/q><\/div><\/div> <\/div><\/div>

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      1993<\/strong><\/h4>\n

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      A Pediatric Oncology Group (POG) study\u00a0evaluating chemotherapy only approaches for\u00a0infants (Baby-POG) is published suggesting that a\u00a0small proportion of infants could be cured without\u00a0radiation therapy.<\/p>\n

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      1990<\/strong><\/h4>\n

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      Introduction of the MRI scan of the spine in\u00a0the staging of medulloblastoma (up to that time,\u00a0spinal staging was performed with myelogram).\u00a0This dramatically improved the ability to detect\u00a0metastases and allowed more robust identification\u00a0of high risk patients with metastatic dissemination.<\/p>\n

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      1980's<\/strong><\/h4>\n

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      Several studies show significant\u00a0neurocognitive impairment in children treated with\u00a0standard doses of craniospinal irradiation,\u00a0specifically young children. Approaches to reduce\u00a0craniospinal irradiation using adjuvant\u00a0chemotherapy are initiated. However, the SIOP 2\u00a0trial concluded that dose reduction was not safe.<\/p>\n

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      1970's<\/strong><\/h4>\n

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      First International Society of Paediatric\u00a0Oncology (SIOP) and Children\u2019s Cancer Study Group\u00a0(CCG) randomised trials with similar design (radiation\u00a0+\/- chemotherapy) that suggest a benefit for\u00a0chemotherapy in a subset of patients.<\/p>\n

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      1969<\/strong><\/h4>\n

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      Staging system proposed by C.H. Chang.\u00a0This staging system was developed in the pre-CT\u00a0scan era and is based on size and invasiveness of\u00a0the tumour at surgery (T stage) and evidence of\u00a0spread outside the posterior fossa (M stage).<\/p>\n

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      1950's<\/strong><\/h4>\n

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      First comprehensive study of\u00a0craniospinal irradiation for medulloblastoma\u00a0leading to three-year survival of over 50%. This\u00a0showed for the first time that a combination of\u00a0surgery and craniospinal irradiation could lead to\u00a0cure and that medulloblastoma was not\u00a0necessarily a fatal disease.<\/p>\n

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      1920's<\/strong><\/h4>\n

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      1. First attempt at x-ray therapy (roentgen\u00a0therapy) by Percival Bailey and Harvey Cushing.\u00a0They found that a subset of patients at autopsy\u00a0in fact had no evidence of medulloblastoma,\u00a0rather radiation necrosis. Led other groups to\u00a0explore radiation therapy as a treatment\u00a0after surgery.<\/li>\n
      2. Harvey Cushing described\u00a0medulloblastoma and performed the initial\u00a0surgeries. It was realized very quickly that\u00a0after surgery, the tumour returns in all cases.<\/li>\n<\/ol>\n

        <\/div><\/div> <\/div><\/div><\/div><\/div>[\/vc_column][vc_column width=”1\/6″][\/vc_column][\/vc_row]<\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"

        [vc_row type=”1″ animation=”fadeIn” margin_top=”-50px”][vc_column][vc_empty_space height=”150px”][\/vc_column][\/vc_row][vc_row type=”1″ animation=”fadeIn” bg_repeat=”repeat” bg_cover=”true” bg_attachment=”true”][vc_column width=”1\/6″][\/vc_column][vc_column width=”2\/3″ animation=”fadeIn”][vc_column_text css_animation=”fadeIn”] History of Medulloblastoma Research (Adapted from Brain Tumour Magazine with permission. Contents researched by SickKids physicians Dr. Vijay Ramaswamy and Dr. Eric Bouffet.)   EACH year medulloblastoma affects five\u00a0children in every one million,\u00a0one of\u00a0the most common malignant brain tumours\u00a0in children. This…<\/p>\n","protected":false},"author":2,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":""},"class_list":["post-23","page","type-page","status-publish","hentry","description-off"],"yoast_head":"\ntimeline - Ramaswamy Lab<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/lab.research.sickkids.ca\/ramaswamy\/timeline\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"timeline\" \/>\n<meta property=\"og:description\" content=\"[vc_row type=”1″ animation=”fadeIn” margin_top=”-50px”][vc_column][vc_empty_space height=”150px”][\/vc_column][\/vc_row][vc_row type=”1″ animation=”fadeIn” bg_repeat=”repeat” bg_cover=”true” bg_attachment=”true”][vc_column width=”1\/6″][\/vc_column][vc_column width=”2\/3″ animation=”fadeIn”][vc_column_text css_animation=”fadeIn”] History of Medulloblastoma Research (Adapted from Brain Tumour Magazine with permission. Contents researched by SickKids physicians Dr. Vijay Ramaswamy and Dr. Eric Bouffet.)   EACH year medulloblastoma affects five\u00a0children in every one million,\u00a0one of\u00a0the most common malignant brain tumours\u00a0in children. This…\" \/>\n<meta property=\"og:url\" content=\"https:\/\/lab.research.sickkids.ca\/ramaswamy\/timeline\/\" \/>\n<meta property=\"og:site_name\" content=\"Ramaswamy Lab\" \/>\n<meta property=\"article:modified_time\" content=\"2018-11-09T14:52:17+00:00\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:label1\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data1\" content=\"6 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\/\/schema.org\",\"@graph\":[{\"@type\":\"WebPage\",\"@id\":\"https:\/\/lab.research.sickkids.ca\/ramaswamy\/timeline\/\",\"url\":\"https:\/\/lab.research.sickkids.ca\/ramaswamy\/timeline\/\",\"name\":\"timeline - Ramaswamy Lab\",\"isPartOf\":{\"@id\":\"https:\/\/lab.research.sickkids.ca\/ramaswamy\/#website\"},\"datePublished\":\"2018-10-17T16:17:53+00:00\",\"dateModified\":\"2018-11-09T14:52:17+00:00\",\"breadcrumb\":{\"@id\":\"https:\/\/lab.research.sickkids.ca\/ramaswamy\/timeline\/#breadcrumb\"},\"inLanguage\":\"en-US\",\"potentialAction\":[{\"@type\":\"ReadAction\",\"target\":[\"https:\/\/lab.research.sickkids.ca\/ramaswamy\/timeline\/\"]}]},{\"@type\":\"BreadcrumbList\",\"@id\":\"https:\/\/lab.research.sickkids.ca\/ramaswamy\/timeline\/#breadcrumb\",\"itemListElement\":[{\"@type\":\"ListItem\",\"position\":1,\"name\":\"Home\",\"item\":\"https:\/\/lab.research.sickkids.ca\/ramaswamy\/\"},{\"@type\":\"ListItem\",\"position\":2,\"name\":\"timeline\"}]},{\"@type\":\"WebSite\",\"@id\":\"https:\/\/lab.research.sickkids.ca\/ramaswamy\/#website\",\"url\":\"https:\/\/lab.research.sickkids.ca\/ramaswamy\/\",\"name\":\"Ramaswamy Lab\",\"description\":\"Translational and Molecular Neuro-Oncology Lab\",\"potentialAction\":[{\"@type\":\"SearchAction\",\"target\":{\"@type\":\"EntryPoint\",\"urlTemplate\":\"https:\/\/lab.research.sickkids.ca\/ramaswamy\/?s={search_term_string}\"},\"query-input\":{\"@type\":\"PropertyValueSpecification\",\"valueRequired\":true,\"valueName\":\"search_term_string\"}}],\"inLanguage\":\"en-US\"}]}<\/script>\n<!-- \/ Yoast SEO Premium plugin. -->","yoast_head_json":{"title":"timeline - Ramaswamy Lab","robots":{"index":"index","follow":"follow","max-snippet":"max-snippet:-1","max-image-preview":"max-image-preview:large","max-video-preview":"max-video-preview:-1"},"canonical":"https:\/\/lab.research.sickkids.ca\/ramaswamy\/timeline\/","og_locale":"en_US","og_type":"article","og_title":"timeline","og_description":"[vc_row type=”1″ animation=”fadeIn” margin_top=”-50px”][vc_column][vc_empty_space height=”150px”][\/vc_column][\/vc_row][vc_row type=”1″ animation=”fadeIn” bg_repeat=”repeat” bg_cover=”true” bg_attachment=”true”][vc_column width=”1\/6″][\/vc_column][vc_column width=”2\/3″ animation=”fadeIn”][vc_column_text css_animation=”fadeIn”] History of Medulloblastoma Research (Adapted from Brain Tumour Magazine with permission. Contents researched by SickKids physicians Dr. Vijay Ramaswamy and Dr. Eric Bouffet.)   EACH year medulloblastoma affects five\u00a0children in every one million,\u00a0one of\u00a0the most common malignant brain tumours\u00a0in children. 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