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Gratitude</a></li> <li class="page_item page-item-4631"><a href="https://www.acco.org/goldenangels/">Golden Angels – Puerto Rico (PR)</a></li> <li class="page_item page-item-12853"><a href="https://www.acco.org/golden-warriors-of-maine-me/">Golden Warriors of Maine – ME</a></li> <li class="page_item page-item-14066"><a href="https://www.acco.org/graces-survivor-story/">Grace’s Survivor Story</a></li> <li class="page_item page-item-6538"><a href="https://www.acco.org/green-family/">Green Family</a></li> <li class="page_item page-item-23"><a href="https://www.acco.org/groups/">Groups</a></li> <li class="page_item page-item-14098"><a href="https://www.acco.org/hannahs-survivor-story/">Hannah’s Survivor Story</a></li> <li class="page_item page-item-1831"><a href="https://www.acco.org/health-related-outcomes-for-hodgkin-disease-survivors/">Health-Related Outcomes for Hodgkin Disease Survivors</a></li> <li class="page_item page-item-31010"><a href="https://www.acco.org/hepatoblastoma-cancer-de-higado/">Hepatoblastoma (Cáncer de Hígado)</a></li> <li class="page_item page-item-1339"><a href="https://www.acco.org/hepatoblastoma/">Hepatoblastoma (Liver Cancer)</a></li> <li class="page_item page-item-170"><a href="https://www.acco.org/hero-beads/">Hero Beads®</a></li> <li class="page_item page-item-37"><a href="https://www.acco.org/history/">History of ACCO</a></li> <li class="page_item page-item-551"><a href="https://www.acco.org/history-timeline/">History Timeline</a></li> <li class="page_item page-item-2"><a href="https://www.acco.org/">Home</a></li> <li class="page_item page-item-1407"><a href="https://www.acco.org/home-2/">Home</a></li> <li class="page_item page-item-3235"><a href="https://www.acco.org/hope4heroes/">Hope 4 Heroes – CO</a></li> <li class="page_item page-item-34438"><a href="https://www.acco.org/hope-amidst-sorrow/">Hope Amidst Sorrow: A Seminar for Bereaved Parents</a></li> <li class="page_item page-item-5188"><a href="https://www.acco.org/hope4ccf/">Hope4CCF – LA</a></li> <li class="page_item page-item-34720"><a href="https://www.acco.org/hospital-organization-resources/">Hospital & Organization Resources</a></li> <li class="page_item page-item-11769"><a href="https://www.acco.org/hospitalnetwork/">Hospital Network Program</a></li> <li class="page_item page-item-1760"><a href="https://www.acco.org/hydrocephalus-shunts-and-gamma-knife/">Hydrocephalus, Shunts, and Gamma Knife</a></li> <li class="page_item page-item-13521"><a href="https://www.acco.org/i-feel-afraid/">I feel afraid.</a></li> <li class="page_item page-item-13503"><a href="https://www.acco.org/i-feel-angry/">I feel angry.</a></li> <li class="page_item page-item-13509"><a href="https://www.acco.org/i-feel-bored/">I feel bored.</a></li> <li class="page_item page-item-13525"><a href="https://www.acco.org/i-feel-disgusted/">I feel disgusted.</a></li> <li class="page_item page-item-13490"><a href="https://www.acco.org/i-feel-happy/">I feel happy.</a></li> <li class="page_item page-item-13494"><a href="https://www.acco.org/i-feel-proud/">I feel proud.</a></li> <li class="page_item page-item-13472"><a href="https://www.acco.org/i-feel-sad/">I feel sad.</a></li> <li class="page_item page-item-13498"><a href="https://www.acco.org/i-feel-surprised/">I feel surprised.</a></li> <li class="page_item page-item-13519"><a href="https://www.acco.org/i-feel-tired/">I feel tired.</a></li> <li class="page_item page-item-1986"><a href="https://www.acco.org/improving-informed-consent-in-childhood-cancer-trials/">Improving Informed Consent in Childhood Cancer Trials</a></li> <li class="page_item page-item-10881"><a href="https://www.acco.org/international/">International Advocacy</a></li> <li class="page_item page-item-33565"><a href="https://www.acco.org/iccd-2024/">International Childhood Cancer Day – 2024</a></li> <li class="page_item page-item-4711"><a href="https://www.acco.org/international-statistics/">International Statistics</a></li> <li class="page_item page-item-14265"><a href="https://www.acco.org/irenes-survivor-story/">Irene’s Survivor Story</a></li> <li class="page_item page-item-1977"><a href="https://www.acco.org/its-only-a-phase-clinical-trials-part-ii/">It’s only a Phase! Clinical Trials Part II</a></li> <li class="page_item page-item-10615"><a href="https://www.acco.org/jake/">Jake’s Dragon Foundation – PA</a></li> <li class="page_item page-item-14329"><a href="https://www.acco.org/jeffs-survivor-story/">Jeff’s Survivor Story</a></li> <li class="page_item page-item-241"><a href="https://www.acco.org/jelsert/">Jel Sert</a></li> <li class="page_item page-item-14399"><a href="https://www.acco.org/jennifers-survivor-story/">Jennifer’s Survivor Story</a></li> <li class="page_item page-item-14176"><a href="https://www.acco.org/jensens-survivor-story/">Jensen’s Survivor Story</a></li> <li class="page_item page-item-14283"><a href="https://www.acco.org/jillians-survivor-story/">Jillian’s Survivor Story</a></li> <li class="page_item page-item-14286"><a href="https://www.acco.org/juanitas-survivor-story/">Juanita’s Survivor Story</a></li> <li class="page_item page-item-2370"><a href="https://www.acco.org/karis-cause/">Karis’ Cause – OH</a></li> <li class="page_item page-item-13446"><a href="https://www.acco.org/kartersisolation/">Karter’s Isolation Story</a></li> <li class="page_item page-item-14109"><a href="https://www.acco.org/karters-survivor-story/">Karter’s Survivor Story</a></li> <li class="page_item page-item-14178"><a href="https://www.acco.org/kaydences-survivor-story/">Kaydence’s Survivor Story</a></li> <li class="page_item page-item-554"><a href="https://www.acco.org/kemper/">Kemper Foods International</a></li> <li class="page_item page-item-36077"><a href="https://www.acco.org/ks-acco/">Kendra Scott Supports Kids with Cancer</a></li> <li class="page_item page-item-6560"><a href="https://www.acco.org/kovach-family/">Kovach Family</a></li> <li class="page_item page-item-11687"><a href="https://www.acco.org/laborinlovebuildinginhope/">Labor in Love: Building in Hope – OR</a></li> <li class="page_item page-item-99"><a href="https://www.acco.org/late-effects/">Late Effects</a></li> <li class="page_item page-item-30421"><a href="https://www.acco.org/leucemias-infantiles/">Leucemias Infantiles</a></li> <li class="page_item page-item-14427"><a href="https://www.acco.org/lilys-survivor-story/">Lily’s Survivor Story</a></li> <li class="page_item page-item-31268"><a href="https://www.acco.org/linfomas-infantiles/">Linfomas Infantiles</a></li> <li class="page_item page-item-4490"><a href="https://www.acco.org/live-newsfeed/">Live Newsfeed</a></li> <li class="page_item page-item-36912"><a href="https://www.acco.org/lived-experience-of-cancer-a-who-study/">Lived Experience of Cancer: A WHO Study</a></li> <li class="page_item page-item-290"><a href="https://www.acco.org/local-groups/">Local Groups</a></li> <li class="page_item page-item-14401"><a href="https://www.acco.org/logans-survivor-story/">Logan’s Survivor Story</a></li> <li class="page_item page-item-2408"><a href="https://www.acco.org/love-for-zac/">Love for Zac – CA</a></li> <li class="page_item page-item-36370"><a href="https://www.acco.org/make-it-cute/">Make It Cute</a></li> <li class="page_item page-item-13433"><a href="https://www.acco.org/masonsisolation/">Mason’s Isolation Story</a></li> <li class="page_item page-item-24088"><a href="https://www.acco.org/matilda-jane/">Matilda Jane</a></li> <li class="page_item page-item-518"><a href="https://www.acco.org/medical-play-kit/">Medical Play Kit</a></li> <li class="page_item page-item-14243"><a href="https://www.acco.org/mias-isolation-story/">Mia’s Isolation Story</a></li> <li class="page_item page-item-7021"><a href="https://www.acco.org/microsoft/">Microsoft</a></li> <li class="page_item page-item-7085"><a href="https://www.acco.org/mission-of-hope/">Mission of Hope – Sean Swarner Cancer Climber</a></li> <li class="page_item page-item-32"><a href="https://www.acco.org/mission-statement-2/">Mission Statement</a></li> <li class="page_item page-item-14383"><a href="https://www.acco.org/mollys-survivor-story/">Molly’s Survivor Story</a></li> <li class="page_item page-item-36393"><a href="https://www.acco.org/name-shirts-are-back-in-2024/">Name Shirts are Back in 2024!</a></li> <li class="page_item page-item-13167"><a href="https://www.acco.org/national-pajama-day/">National Pajama Day</a></li> <li class="page_item page-item-1349"><a href="https://www.acco.org/neuroblastoma/">Neuroblastoma</a></li> <li class="page_item page-item-32359"><a href="https://www.acco.org/neuroblastoma-2/">Neuroblastoma</a></li> <li class="page_item page-item-1988"><a href="https://www.acco.org/neuropsychological-testing-an-excerpt-from-educating-the-child/">Neuropsychological Testing: An Excerpt from Educating the Child</a></li> <li class="page_item page-item-1990"><a href="https://www.acco.org/new-approaches-for-resistant-brain-tumors/">New Approaches for Resistant Brain Tumors</a></li> <li class="page_item page-item-40"><a href="https://www.acco.org/news-and-press/">News and Press</a></li> <li class="page_item page-item-4365"><a href="https://www.acco.org/newsfeed-test/">Newsfeed Test</a></li> <li class="page_item page-item-11391"><a href="https://www.acco.org/nickys-heart-of-gold-pa/">Nicky’s Heart of Gold – PA</a></li> <li class="page_item page-item-13438"><a href="https://www.acco.org/noahsisolation/">Noah’s Isolation Story</a></li> <li class="page_item page-item-11076"><a href="https://www.acco.org/orangeribbon/">Orange Ribbon Foundation</a></li> <li class="page_item page-item-1746"><a href="https://www.acco.org/osteonecrosis-a-source-of-bone-pain-and-loss-of-function/">Osteonecrosis: A Source of Bone Pain and Loss of Function</a></li> <li class="page_item page-item-7340"><a href="https://www.acco.org/goodwillchill/">Otter Pop Vibes Tour #GoodWillChill</a></li> <li class="page_item page-item-186"><a href="https://www.acco.org/outside-resources/">Outside Resources</a></li> <li class="page_item page-item-1992"><a href="https://www.acco.org/palliative-or-hospice-care-does-my-child-need-this-service/">Palliative or Hospice Care: Does my child need this service?</a></li> <li class="page_item page-item-246"><a href="https://www.acco.org/palmco/">Palmco</a></li> <li class="page_item page-item-10142"><a href="https://www.acco.org/pwap/">Paranormal With a Purpose – FL</a></li> <li class="page_item page-item-2438"><a href="https://www.acco.org/paulandthedragon/">Paul and the Dragon</a></li> <li class="page_item page-item-166"><a href="https://www.acco.org/paul-and-the-dragon-dvd/">Paul and the Dragon Video</a></li> <li class="page_item page-item-13424"><a href="https://www.acco.org/paxtonsisolation/">Paxton’s Isolation Story</a></li> <li class="page_item page-item-34857"><a href="https://www.acco.org/pediatric-cancer-teaching-resources-for-professionals-educators/">Pediatric Cancer Teaching Resources For Professionals & Educators</a></li> <li class="page_item page-item-396"><a href="https://www.acco.org/pjammin/">PJammin® For Kids with Cancer</a></li> <li class="page_item page-item-7315"><a href="https://www.acco.org/pjamminfaq/">PJammin® Frequently Asked Questions</a></li> <li class="page_item page-item-1764"><a href="https://www.acco.org/ports-and-central-lines/">Ports and Central Lines</a></li> <li class="page_item page-item-1994"><a href="https://www.acco.org/practical-genetics-in-cancer-the-human-genetic-code/">Practical Genetics in Cancer: The Human Genetic Code</a></li> <li class="page_item page-item-35046"><a href="https://www.acco.org/preventing-hearing-loss-from-chemo/">Preventing Hearing Loss from Chemo</a></li> <li class="page_item page-item-13222"><a href="https://www.acco.org/print-at-home-coloring-pages/">Print-at-Home Coloring Pages</a></li> <li class="page_item page-item-10883"><a href="https://www.acco.org/proclamations/">Proclamation Language</a></li> <li class="page_item page-item-14447"><a href="https://www.acco.org/quick-links/">Quick Links</a></li> <li class="page_item page-item-404"><a href="https://www.acco.org/raise-awareness-2/">Raise Awareness</a></li> <li class="page_item page-item-1141"><a href="https://www.acco.org/raise-awareness/">Raise Awareness</a></li> <li class="page_item page-item-530"><a href="https://www.acco.org/read-about-it-acco-publications/">Read About It: ACCO Publications</a></li> <li class="page_item page-item-13870"><a href="https://www.acco.org/read-alongs-with-acco/">Read Alongs with ACCO</a></li> <li class="page_item page-item-1996"><a href="https://www.acco.org/relapsed-all-chemotherapy-vs-transplant/">Relapsed ALL: Chemotherapy vs Transplant</a></li> <li class="page_item page-item-1998"><a href="https://www.acco.org/relapsed-all-questions-for-parents-to-ask/">Relapsed ALL: Questions for Parents to Ask</a></li> <li class="page_item page-item-10"><a href="https://www.acco.org/research/">Research</a></li> <li class="page_item page-item-208"><a href="https://www.acco.org/research-articles/">Research Articles</a></li> <li class="page_item page-item-1766"><a href="https://www.acco.org/researching-the-medical-literature/">Researching the Medical Literature</a></li> <li class="page_item page-item-1352"><a href="https://www.acco.org/retinoblastoma/">Retinoblastoma</a></li> <li class="page_item page-item-1355"><a href="https://www.acco.org/rhabdoid-tumors/">Rhabdoid Tumors</a></li> <li class="page_item page-item-5985"><a href="https://www.acco.org/ribbons-of-gold/">Ribbons of Gold – WI</a></li> <li class="page_item page-item-6423"><a href="https://www.acco.org/rock-bottom/">Rock Bottom</a></li> <li class="page_item page-item-6566"><a href="https://www.acco.org/rbfamilies2016/">Rock Bottom Holiday Families</a></li> <li class="page_item page-item-1406"><a href="https://www.acco.org/sample-page-2/">Sample Page</a></li> <li class="page_item page-item-14530"><a href="https://www.acco.org/sarcoma-awareness-month/">Sarcoma Awareness Month</a></li> <li class="page_item page-item-1358"><a href="https://www.acco.org/sarcomas/">Sarcomas</a></li> <li class="page_item page-item-32674"><a href="https://www.acco.org/sarcomas-2/">Sarcomas</a></li> <li class="page_item page-item-6585"><a href="https://www.acco.org/scherff-family/">Scherff Family</a></li> <li class="page_item page-item-13384"><a href="https://www.acco.org/sew-to-save-lives/">Sew to Save Lives</a></li> <li class="page_item page-item-14250"><a href="https://www.acco.org/sing-along-with-acco/">Sing Along with ACCO</a></li> <li class="page_item page-item-391"><a href="https://www.acco.org/sitemap/">Sitemap</a></li> <li class="page_item page-item-13309"><a href="https://www.acco.org/social-isolation-stories/">Social Isolation Stories</a></li> <li class="page_item page-item-13045"><a href="https://www.acco.org/stamp/">Stamp Out Childhood Cancer</a></li> <li class="page_item page-item-123"><a href="https://www.acco.org/start-a-division/">Start a Division or Group</a></li> <li class="page_item page-item-7261"><a href="https://www.acco.org/state/">State</a></li> <li class="page_item page-item-12073"><a href="https://www.acco.org/state-comprehensive-cancer-control-plan/">State Comprehensive Cancer Control Plan</a></li> <li class="page_item page-item-13667"><a href="https://www.acco.org/stevens-isolation-story/">Steven’s Isolation Story</a></li> <li class="page_item page-item-1730"><a href="https://www.acco.org/stories-from-adult-and-child-survivors/">Stories from Adult and Child Survivors</a></li> <li class="page_item page-item-7210"><a href="https://www.acco.org/kobie/">Strength to Survive Childhood Cancer Foundation – HI</a></li> <li class="page_item page-item-1725"><a href="https://www.acco.org/suicidal-thoughts-and-attempts-in-adult-survivors/">Suicidal Thoughts and Attempts in Adult Survivors</a></li> <li class="page_item page-item-6552"><a href="https://www.acco.org/sullivan-family/">Sullivan Family</a></li> <li class="page_item page-item-13972"><a href="https://www.acco.org/survivor-stories/">Survivor Stories</a></li> <li class="page_item page-item-30176"><a href="https://www.acco.org/survivor-stories-alec/">Survivor Stories: Alec</a></li> <li class="page_item page-item-30156"><a href="https://www.acco.org/survivor-stories-alex/">Survivor Stories: Alex</a></li> <li class="page_item page-item-30124"><a href="https://www.acco.org/survivor-stories-ashley/">Survivor Stories: Ashley</a></li> <li class="page_item page-item-30164"><a href="https://www.acco.org/survivor-stories-cara/">Survivor Stories: Cara</a></li> <li class="page_item page-item-30168"><a href="https://www.acco.org/survivor-stories-jordan/">Survivor Stories: Jordan</a></li> <li class="page_item page-item-30239"><a href="https://www.acco.org/survivor-stories-meg/">Survivor Stories: Meg</a></li> <li class="page_item page-item-30679"><a href="https://www.acco.org/survivor-stories-payal/">Survivor Stories: Payal</a></li> <li class="page_item page-item-30161"><a href="https://www.acco.org/survivor-stories-ronald/">Survivor Stories: Ronald</a></li> <li class="page_item page-item-30174"><a href="https://www.acco.org/survivor-stories-taylor/">Survivor Stories: Taylor</a></li> <li class="page_item page-item-30127"><a href="https://www.acco.org/survivor-stories-tj/">Survivor Stories: TJ</a></li> <li class="page_item page-item-30171"><a href="https://www.acco.org/survivor-stories-victoria/">Survivor Stories: Victoria</a></li> <li class="page_item page-item-198"><a href="https://www.acco.org/targeted-therapeutics/">Targeted Therapeutics</a></li> <li class="page_item page-item-2000"><a href="https://www.acco.org/targeted-therapeutics-workshop-at-international-cancer-congress/">Targeted Therapeutics Workshop at International Cancer Congress</a></li> <li class="page_item page-item-2002"><a href="https://www.acco.org/targeting-cancer-in-the-21st-century/">Targeting Cancer In The 21st Century</a></li> <li class="page_item page-item-5405"><a href="https://www.acco.org/team-go-gold/">Team Go Gold</a></li> <li class="page_item page-item-526"><a href="https://www.acco.org/teen-journal/">Teen Journal</a></li> <li class="page_item page-item-6357"><a href="https://www.acco.org/thank-you/">Thank you</a></li> <li class="page_item page-item-1852"><a href="https://www.acco.org/thank-you-for-ordering/">Thank You For Ordering</a></li> <li class="page_item page-item-16373"><a href="https://www.acco.org/brain-tumor-charter-of-rights/">The Brain Tumour Patients’ Charter of Rights</a></li> <li class="page_item page-item-4129"><a href="https://www.acco.org/madison/">The Miracle of Madison – MD</a></li> <li class="page_item page-item-1732"><a href="https://www.acco.org/the-problem-of-pain-in-childhood-cancer-survivors/">The Problem of Pain in Childhood Cancer Survivors</a></li> <li class="page_item page-item-5922"><a href="https://www.acco.org/xen/">Through Xen – CT</a></li> <li class="page_item page-item-1582"><a href="https://www.acco.org/timeline/">Timeline</a></li> <li class="page_item page-item-27985"><a href="https://www.acco.org/tipos-de-cancer-infantil/">Tipos de Cáncer Infantil</a></li> <li class="page_item page-item-2004 current_page_item"><a href="https://www.acco.org/treating-high-risk-neuroblastoma-at-the-turn-of-the-century/" aria-current="page">Treating High-Risk Neuroblastoma at the Turn of the Century</a></li> <li class="page_item page-item-1770"><a href="https://www.acco.org/treatment-centers-for-childhood-cancers/">Treatment Centers for Childhood Cancers</a></li> <li class="page_item page-item-86"><a href="https://www.acco.org/treatment-2/">Treatment Options</a></li> <li class="page_item page-item-2745"><a href="https://www.acco.org/triderma/">TriDerma Supports ACCO!</a></li> <li class="page_item page-item-32712"><a href="https://www.acco.org/tumor-de-wilms-y-otros-tumores-renales-infantiles/">Tumor de Wilms y Otros Tumores Renales Infantiles</a></li> <li class="page_item page-item-32701"><a href="https://www.acco.org/tumores-de-la-medula-espinal/">Tumores de la Médula Espinal</a></li> <li class="page_item page-item-32667"><a href="https://www.acco.org/tumores-rabdoides/">Tumores Rabdoides</a></li> <li class="page_item page-item-73"><a href="https://www.acco.org/types-of-childhood-cancer/">Types of Childhood Cancer</a></li> <li class="page_item page-item-77"><a href="https://www.acco.org/us-childhood-cancer-statistics/">US Childhood Cancer Statistics</a></li> <li class="page_item page-item-14635"><a href="https://www.acco.org/virtual-advocacy/">Virtual Advocacy</a></li> <li class="page_item page-item-36325"><a href="https://www.acco.org/voyageur-outward-bound-school/">Voyageur Outward Bound School</a></li> <li class="page_item page-item-21662"><a href="https://www.acco.org/wacco/">WACCO</a></li> <li class="page_item page-item-6544"><a href="https://www.acco.org/walsh-family/">Walsh Family</a></li> <li class="page_item page-item-27552"><a href="https://www.acco.org/ways-to-give/">Ways To Give</a></li> <li class="page_item page-item-412"><a href="https://www.acco.org/we-can-help/">We Can Help</a></li> <li class="page_item page-item-285"><a href="https://www.acco.org/riley/">We Love Riley Fan Club – MA</a></li> <li class="page_item page-item-917"><a href="https://www.acco.org/websites-for-kids-with-cancer/">Websites for Kids with Cancer</a></li> <li class="page_item page-item-36534"><a href="https://www.acco.org/what-about-kids-symposium/">What About Kids Symposium</a></li> <li class="page_item page-item-33678"><a href="https://www.acco.org/what-about-kids/">What About Kids?</a></li> <li class="page_item page-item-35195"><a href="https://www.acco.org/whats-cookin/">What’s Cookin’?</a></li> <li class="page_item page-item-11176"><a href="https://www.acco.org/whynotkids/">Why Not Kids®</a></li> <li class="page_item page-item-201"><a href="https://www.acco.org/why-research-is-needed/">Why Research is Needed</a></li> <li class="page_item page-item-4267"><a href="https://www.acco.org/child4child/">Will you join us?</a></li> <li class="page_item page-item-1361"><a href="https://www.acco.org/wilms-tumor-and-other-childhood-kidney-tumors/">Wilms’ Tumor and Other Childhood Kidney Tumors</a></li> <li class="page_item page-item-12756"><a href="https://www.acco.org/wolfpack-childhood-cancer-foundation-va/">WolfPack Childhood Cancer Foundation – VA</a></li> <li class="page_item page-item-4746"><a href="https://www.acco.org/youcaring/">YouCaring</a></li> <li class="page_item page-item-2006"><a href="https://www.acco.org/your-child-and-the-individualized-education-program-iep/">Your Child and the Individualized Education Program (IEP)</a></li> <li class="page_item page-item-10582"><a href="https://www.acco.org/foundinghope/kinskids/">Kin’s Kids – CA</a></li> <li class="page_item page-item-25766"><a href="https://www.acco.org/foundinghope/megs-giveback-giving-back-a-little-childhood-va/">Meg’s Giveback – “Giving 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class="col col-6 links"> <div id="flex-item" class="w-100 d-block"> <a href="https://www.acco.org">Current Specials </a> <a href="https://www.acco.org">Get Directions </a> <a href="https://www.acco.org/photo-gallery/">Photo Gallery </a> </div> </div>  </div> </div>  <div class="container-fluid"> <div class="row"> <div class="bg-container" style="background-image: url(https://www.acco.org/wp-content/themes/acco-new/img/bg-slider.png)"><div class="bg-overlay"><div class="container"><h1 class="entry-title">Treating High-Risk Neuroblastoma at the Turn of the Century</h1></div></div></div> </div> </div> <div id="one-column"> <div class="container"> <div class="row"> <div id="primary" class="col-md-12"> <div class="content-wrapper"> <article id="post-2004" class="post-2004 page type-page status-publish hentry"> <div class="entry-content"> <h3><strong>TREATING HIGH-RISK NEUROBLASTOMA AT THE TURN OF THE CENTURY</strong></h3> <p><em>by C. Patrick Reynolds, MD PhD & Beth Hasenauer, RN MS</em> Source: Spring 2001 CCCF Newsletter</p> <p><img fetchpriority="high" decoding="async" class="size-full wp-image-12211 alignright" src="https://www.acco.org/wp-content/uploads/2015/03/Neuroblastoma-cancer.jpg" alt="Neuroblastoma cancer" width="321" height="427" srcset="https://www.acco.org/wp-content/uploads/2015/03/Neuroblastoma-cancer.jpg 321w, https://www.acco.org/wp-content/uploads/2015/03/Neuroblastoma-cancer-226x300.jpg 226w, https://www.acco.org/wp-content/uploads/2015/03/Neuroblastoma-cancer-300x399.jpg 300w" sizes="(max-width: 321px) 100vw, 321px" />Neuroblastoma is a solid tumor of childhood that arises in the nervous system, outside of the brain. The goal of this article is to provide a guide to the initial treatment options available for children with high-risk neuroblastoma. Also reviewed, will be the design and conduct of clinical trials. This information will be of interest to parents dealing with other childhood cancers.</p> <p>During the last part of the 20th century, clinical trials have shown that the basis for treating high-risk neuroblastoma should consist of induction chemotherapy, consolidation with high dose chemotherapy + stem cell transplant. The stem cell transplants use the patient’s own previously stored stem cells obtained from either the bone marrow or peripheral blood (PBSC) to replace the bone marrow, which is destroyed by the high-dose chemotherapy. Patients also receive local radiation to tumor sites, followed by posttransplant maintenance treatment with 13-cis-retinoic acid (Accutane). 13-cis-retinoic acid is aimed at eliminating any remaining tumor cells that are possibly left after the transplant. These established principles apply to “up-front” therapy of high-risk neuroblastoma.</p> <p>To date, a single large clinical study with long-term survival data (the Childrens Cancer Group CCG-3891 study) has employed all of these therapeutic principles uniformly in a large group of patients beginning at diagnosis. Based on the CCG data, a child diagnosed with high-risk neuroblastoma when treated with the above approaches, can expect an estimated 40% probability of disease- free survival four years from diagnosis. Potential improvements in all components of therapy (induction chemotherapy, intensive consolidation with stem cell transplant, and post-transplant therapy) have occurred since the CCG-3891 study. Thus, it is reasonable to expect the potential for a higher disease- free survival for high-risk neuroblastoma in ongoing and future clinical trials.</p> <p>For those patients in whom the tumor progressively grows during or after therapy, the chances of survival are reduced. Because there are no established effective treatments for such patients, therapies listed above and/or highly experimental therapies with unknown risks may be appropriate for such patients.</p> <h3><strong>WHAT IS HIGH-RISK NEUROBLASTOMA?</strong></h3> <p>The clinical behavior of neuroblastoma is highly variable, with some tumors being easily treatable, but the majority being very aggressive. This article will only address therapy of high-risk neuroblastoma. The treatment of low or intermediate risk tumors is very different from treating high-risk disease. All patients with stage 4 disease diagnosed after one year of age are classified in the high-risk category. In stage 4 disease, the neuroblastoma tumor cells have already spread (or metastasized) to other sites in the body, such as the bone or bone marrow. Essentially all patients who have tumors with many copies (or amplification) of the MYCN oncogene also have high-risk disease, even if they do not have evidence of the tumor having spread. Given the aggressiveness of the tumor type, it is accepted practice to treat high-risk neuroblastoma patients with intensive therapy, to increase the probability of cure. Most pediatric oncologists agree that even with optimal current intensive therapy, the aggressive nature of this disease warrants entering as many of these children as possible on clinical trials that may identify improved forms of treatment.</p> <h3><strong>CLINICAL TRIALS</strong></h3> <p>Clinical trials are research studies that test a new approach to therapy. Phase III clinical trials focus on a particular disease and ask specific scientific questions, with the long-term goal of defining the best approach to treatment by comparing one therapy to another. These large studies test a new treatment/ procedure in comparison to the current standard treatment by using randomized assignment to determine which of these approaches offer an improvement in terms of outcome and patient safety as compared to the current standard. Those patients who cannot participate in a clinical trial should receive therapy that has been proven in previous clinical trials to be safe and to deliver the best-proven probability of achieving long-term survival.</p> <p>An advantage to participating in a clinical trial is that the patient receives a therapeutic approach that has been mapped out and reviewed by a team of investigators who specialize in the disease being studied.</p> <p>Participation in clinical trials allows patients access to state-of-the-art treatment for that disease and also the chance of being among the first to benefit from a new treatment that may be more effective.</p> <p>All clinical trials are reviewed by the committee for protection of human subjects (also known as Institutional Review Board or IRB), at the institution where the patient is treated. This review ensures that the rights of the patient will be upheld and protected and that the patient will not be exposed to any unnecessary or extreme risk if he/she agrees to participate in the clinical trial.</p> <p>The larger the organization carrying out the trial, the greater the review of the plan of therapy. For example, a phase III cooperative group trial (in pediatric oncology, a nationwide trial) would be reviewed by many pediatric oncologists, surgeons, pathologists, radiation oncologists, nurses, statisticians, etc in the cooperative group, by the National Cancer Institute’s Cancer Treatment Evaluation Program (CTEP), and by the IRB’s of many dozens of institutions.</p> <p>There are currently several different clinical trials in the United States for newly diagnosed high-risk neuroblastoma. Most of the these trials utilize initial therapy (induction chemotherapy and perhaps surgery), followed by high-dose chemotherapy with stem cell transplant using the patient’s own stem cells. Most studies also employ local radiation, and after completion of all cytotoxic therapy (including stem cell transplant and radiation), Accutane is given for six months. Phase III trials conducted by the national cooperative group (The Childrens Oncology Group, or COG) occur without change over more then 3 years, so we will review those trials in detail. Table 1 summarizes most of the modalities of therapy currently being tested in clinical trials for high risk neuroblastoma, including phase I and phase II studies.</p> <h3><strong>CHILDRENS ONCOLOGY GROUP (COG) PHASE III STUDIES</strong></h3> <p>The Childrens Oncology Group is a national group of physicians, nurses, and other specialists devoted to the study of childhood cancer. Phase III trials run by cooperative groups such as the COG help to establish state of the art cancer therapy. There are currently 2 planned COG phase III trials for high-risk neuroblastoma. Both of these trials will enroll the same group of patients because the treatments being tested are sequential in nature. This means that a patient enrolled on the first study (known as A3973) may, but is not required to, enroll on the study that comes later in therapy, which is known as ANBL0032. However, patients who do not enroll on the A3973 study beginning at diagnosis are not eligible to participate in the ANBL0032 study. This requirement is to insure the statistical validity of the studies.</p> <p>The A3973 study, which opened on February 10, 2001 employs very aggressive multi-drug induction chemotherapy, during which patient’s PBSC are harvested, ideally after 2 cycles of chemotherapy. The major research question being asked in this study is: Does selective removal (purging) of tumor cells from PBSC improve the tumor-free survival of patients given a stem cell transplant? To address this question, half of the patients are randomized to have their stem cells treated with antibodies attached to magnetic beads, which are then used to remove any residual tumor cells that might be remaining in the PBSC. The other half have their untreated stem cells stored for subsequent use. After successfully storing purged or un-purged PBSC, patients will complete 4 additional cycles of chemotherapy (for a total of 6 cycles), followed by intensive myeloablative chemotherapy and the PBSC reinfusion. The myeloablative therapy used in A3973 is known as CEM-LI (carobplatin, etoposide, melphalan, local irradiation). Patients receive the local radiation after the stem cell transplant to the primary tumor site and other sites of known metastases, followed by 6 months of Accutane. Patients on A3973 are eligible to enter the ANBL0032 study.</p> <p>The ANBL0032 study is testing a monoclonal antibody (ch14.18) that attaches to neuroblastoma cells which have a molecule called GD2 on their surface. Once the antibody attaches to the GD2 it helps the tumor cells to be destroyed. This antibody does not attach to most normal cells because they do not have GD2 on their surface. Laboratory experiments and small clinical trials suggest that ch14.18 can help the body’s own immune cells to destroy neuroblastoma cells. These immune cells include cells that are activated by GM-CSF (monocytes and neutrophils) and cells that are activated by IL-2 (lymphocytes). The antibody ch14.18 + GM-CSF or IL-2 will be given after completion of intensive therapy supported by PBSC infusion (A3973 therapy). In addition, 13-cis-retinoic acid (Accutane) will also be given in between cycles of therapy with ch14.18 + GM-CSF or IL-2. The purpose of giving antibody therapy and 13-cis-retinoic acid is to maximize the chances of eliminating any residual neuroblastoma tumor cells (known as minimal residual disease) that may be left after intensive therapy, such as that given in A3973.</p> <p><strong>Recurrent or Progressive Neuroblastoma:</strong> High-risk neuroblastoma patients who develop progressively growing tumors during therapy, or have tumor recurrence after chemotherapy, are encouraged to enter into phase I or II clinical trials that test new approaches to therapy. Some of these studies are carried out within the COG, some within a multi-institutional consortium funded by the National Cancer Institute known as the New Approaches to Neuroblastoma Therapy (NANT) Consortium, and some within individual institutions. Examples of such studies are included in Table 1 below. Because the toxicity (especially the long term toxicities) of these new therapies are not fully known, and because the ability of these therapies to improve outcome for patients is not proven, many of these new approaches are limited to testing in patients with recurrent disease.</p> <h3><strong>MODALITIES OF THERAPY CURRENTLY IN CLINICAL TRIALS FOR HIGH-RISK NEUROBLASTOMA</strong></h3> <p><strong>Induction chemotherapy.</strong> Chemotherapy that doesn’t require marrow or PBSC support. Examples of drugs used include cyclophosphamide, cisplatin, carboplatin, vincristine, doxorubicin, etoposide, ifosfamide, and topotecan.</p> <p><strong>Surgery:</strong> Partial or total surgical removal of the tumor.</p> <p><strong>Local Radiation:</strong> Radiation given to a localized area that includes the tumor.</p> <p><strong>Myeloablative Therapy:</strong> Very intensive chemotherapy or chemotherapy + total body irradiation that destroys the marrow cells, requiring the infusion of marrow or PBSC to restore marrow function. Myeloablative therapy approaches currently being tested include those with intensive chemotherapy, those with intensive chemotherapy + local irradiation, and multiple rounds of myeloablative therapy (tandem transplants).</p> <p><strong>Antibody Therapy:</strong> Administration of a monoclonal antibody that attaches to tumor cells, of ten together with factors called cytokines that stimulate white blood cells (attached to the tumor via the antibody) to kill the tumor cell. Examples of antibody therapy include the ch14.18 antibody, the 3F8 antibody, and a new designer molecule (called an immunocytokine) in which the hu14.18 antibody (an anti-GD2-antibody) is fused together with the IL-2 cytokine.</p> <p><strong>Retinoid Therapy: </strong>Administration of high doses of a drug that is derived from vitamin- ”A”, which has an anti-tumor effect. Retinoids usually have very little or no marrow cytotoxicity and so they are employed soon after myeloablative therapy. Accutane (13- cis-retinoic acid) is a retinoid that causes the neuroblastoma cells to stop growing and differentiate (mature) into more normal appearing cells. Fenretinide is a newer retinoid that, rather then inducing tumor cell differentiation, kills neuroblastoma cells.</p> <p><strong>MIBG:</strong> Administration of high doses of a radioactive chemical selectively taken up by neuroblastoma cells. The MIBG molecule is made with radioactive iodine (131I), which is why the thyroid has to be protected during such therapy. The concentration of the MIBG at the tumor results from the tumor pulling in the MIBG, concentrating the radiation into the tumor. This provides very high doses of radiation to the tumor cells.</p> <p><strong>Vaccine Therapy:</strong> Injection of substances into patients that are designed to stimulate the immunological system to attack the tumor. Examples of such vaccines include tumor cells that have been engineered to make cytokines (those molecules that stimulate the immune system) or antibodies that are designed to elicit an antibody response that will attack the tumor. Antibodies produced by the patient in response to the vaccine could be effective in attacking neuroblastoma cells. Such antibodies are known as “anti-idiotypic antibodies”. Another approach being tested involves genetically engineering neuroblastoma cells so that the tumor cells make a cytokine, irradiating those cells to prevent them from forming tumors, and injecting those cells into the patient to stimulate the immune system.</p> <h3><strong>RESOURCES FOR FURTHER INFORMATION</strong></h3> <p>The internet provides a medium for rapid exchange of information. The following are just some of the information resources available to parents of children with neuroblastoma on “the net”:</p> <p>The NBLASTOMA mailing list is an automated email mailing list where parents of children with neuroblastoma can communicate with one another. In addition to being able to join the list, one can find the archives of the list (which contains a lot of information and discussion in previous posts to the list). The list web site is: <a href="https://web.archive.org/web/20120322110731/http:/listserv.acor.org/archives/n-blastoma.html">listserv.acor.org/archives/n-blastoma.html</a> (http://listserv.acor.org/SCRIPTS/WA-ACOR.EXE?A0=N-BLASTOMA)</p> <p>National Cancer Institute (NCI) site devoted to cancer clinical trials: <a href="https://web.archive.org/web/20120322110731/http:/www.cancer.gov/clinicaltrials">www.cancer.gov/clinicaltrials</a></p> <p>The COG web site: <a href="https://web.archive.org/web/20120322110731/http:/www.curesearch.org/">www.curesearch.org</a></p> <p>The New Approaches to Neuroblastoma Therapy (NANT) web site: www.nant.org</p> <p>Acknowledgements. The authors thank Dr. Robert Seeger and Dr. Clarke Anderson of Childrens Hospital Los Angeles for helpful review of, and suggestions concerning, this article.</p> <p>ACCO would like to thank Dr. Patrick Reynolds, MD PhD and Beth Hasenauer, RN MS, of Children’s Hospital Los Angeles for their on-going commitment towards the improved care of children with neuroblastoma and the writing of this invaluable article.</p> <h3><strong>More about Childhood Neuroblastoma Cancers:</strong></h3> <ul> <li><a href="https://www.acco.org/blog/about-childhood-neuroblastoma-cancer-detection-and-diagnosis/">About Childhood Neuroblastoma Cancer – Detection and Diagnosis</a></li> <li><a href="https://www.acco.org/blog/childhood-neuroblastoma-cancer-causes-risk-factors-and-prevention/">Causes, Risk Factors, and Prevention of Childhood Neuroblastoma Cancer</a></li> <li><a href="https://www.acco.org/blog/neuroblastoma-childhood-cancer-signs-and-symptoms/">What are the signs and symptoms of Childhood Neuroblastoma Cancer?</a></li> <li><a href="https://www.acco.org/blog/childhood-neuroblastoma-treatment/">Childhood Neuroblastoma Cancer Treatment</a></li> <li><a href="https://www.acco.org/blog/childhood-neuroblastoma-cancer-stages-and-prognosis/">Childhood Neuroblastoma Cancer – Stages and Prognosis</a></li> <li><a href="https://www.acco.org/blog/what-is-the-expected-life-span-of-childhood-neuroblastoma-cancer/">What is the expected life span of Childhood Neuroblastoma Cancer?</a></li> <li><a href="https://www.acco.org/blog/after-treatment-living-as-a-childhood-neuroblastoma-cancer-survivor/">After Treatment – Living as a Childhood Neuroblastoma Cancer Survivor</a></li> </ul> </div> <footer class="entry-meta"> </footer> </article> <div id="comments"> </div> </div> </div> </div> </div> </div> </div> <footer id="footer"> <div id="footer-info"> <div class="bottom"> <div class="container wow fadeIn" data-wow-duration="1.75s" data-wow-offset="100"> <div class="row py-4"> <div id="footer-1" class="col-12 my-1 d-none d-md-block"> <div class="row"> <div class="col-md-2"> <img class="img-fluid d-block mx-auto" src="https://www.acco.org/wp-content/themes/acco-new/img/logo-footer.png" /> </div> <div class="col-md-10"> <p class="mt-4">The American Childhood Cancer Organization is a 501(c)(3) public charity, whose programs and services are funded entirely by private donations, foundation grants, and corporate contributions. 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