Talk:Neuroblastoma

N-myc
Just included some info on n-myc amplification. I believe this can occur in up to 80% of cases so it should be included.Hoganpc (talk) 14:20, 16 April 2012 (UTC)

Review
- recent Lancet review JFW | T@lk  12:22, 24 June 2007 (UTC)

3F8
I'm wondering what people think about creating a new page for discussion of the 3F8 antibody. Space could also be dedicated to discussion of Dr. Cheung's hu3F8. I suppose that a section could be added to this page, instead. Thoughts? MeredithParmer (talk) 07:12, 19 February 2008 (UTC)
 * I think it is a great idea! By the way, I did mention the humanized 3F8 effort, and spent a fair amount of time looking for a good reference. Since I could not find any, I took it back out. Can you supply a reference? Thanks for the excellent work! DMLudwinski (talk) 15:52, 19 February 2008 (UTC) I just looked at the Monoclonal antibody therapy article and perhaps you may be able to add a section to it for 3F8? A thought. DMLudwinski (talk) 17:39, 19 February 2008 (UTC)
 * I've created a stub for 3F8. --Arcadian (talk) 00:16, 20 February 2008 (UTC)

Etiology (Aetiology)
Changed "prevention" section to "etiology" and provided some up to date links to peer reviewed journals. Previous link was to a tabloid article that reported a beneficial effect of taking multivitamins, when the study was funded by a (you guessed it!) multivitamin company. Nor did it appear in peer reviewed journal. Apologies for number of separate page edits, but this was my first go. Ironick 10:37, 5 September 2007 (UTC)

Diagnosis
"The diagnosis is usually confirmed by a surgical pathologist, taking into account the clinical presentation, microscopic findings, and other laboratory tests. On microscopy, the tumor cells are typically described as small, round and blue, and rosette patterns (Homer-Wright pseudo-rosettes) may be seen. A variety of immunohistochemical stains are used by pathologists to distinguish neuroblastomas from histological mimics, such as rhabdomyosarcoma, Ewing's sarcoma, lymphoma and Wilms' tumor. The N-myc amplification is characteristic, and sometimes electron microscopy is also required." This contribution of mine was removed without discussion. I am a pathologist but have written it with the intelligent layman in mind. The present reference to neuron-specific enolase is wrong, and the whole paragraph was deleted without discussion. I would find it helpful if people explained their need to remove great slabs of info. Would fellow users care to comment? Hovea 22:55, 10 September 2007 (UTC)

Agreed, no idea why that should be excluded. I like the pathological description. I think this section needs work, perhaps even splitting "symptoms" from the diagnosis section, where less technical language can be used. Then this pathological info can be put back into the diagnosis/identification section. I really don't like the "great masquerader" line (unless it can be cited). Let me know your thoughts. Also the article needs some prevalence and survival data, as an Epidemiologist I will have a look and update this, I think Little 1999 (ISBN 92-832-2149-4) is likely to be the best source. Ironick 10:47, 11 September 2007 (UTC)

Thanks Ironick. I'm with you on this one & I've made a start. Hovea 23:07, 11 September 2007 (UTC)

I just noticed the above quoted material in in the article twice. Where do you think it fits best? DMLudwinski (talk) 16:12, 15 December 2007 (UTC)
 * I have removed the second instance of the duplicated text. --Arcadian (talk) 19:06, 15 December 2007 (UTC)

Changes to risk assignment and staging
I think this section should be changed to reflect the new INRG plan (ref Lancet June 2007 Maris et al). The stages will be called L1, L2, M and MS, and 12-18 month olds without N-myc amplification will be no longer considered high-risk (moved to intermediate risk).

This change in classification with 12-18 month olds (N-myc non-amp) started in the COG May 2004.

This material was also presented at the 2007 ASCO meeting, and virtual presentations are viewable online at ASCO Pediatric Cancers (Neuroblastoma Pediatric Cancer I and Neuroblastoma---Recent Advances in Biology and Therapy Education session) see Dr S Cohn abstract 9503

Thanks for the excellent work on this page! I would personally like to see a LOT more on pathology! DMLudwinski (talk) 23:12, 11 December 2007 (UTC)

(talk) 18:53, 11 December 2007 (UTC)
 * I have added a brief reference to this, but since you are familiar with the subject, I encourage you to expand it. (If possible, it would be more sustainable to cite the journal articles, rather than citing the videos.) --Arcadian (talk) 16:29, 13 December 2007 (UTC)

Pathology image
Arcadian, the image is great (as are other improvements to the article)! I noticed the image added is ganglioneuroblastoma, and checking the NCI link, there is a image of neuroblastoma also, showing the distinctive rosettes. Would that be a better image to include? Or both--since ganglioneuroblastoma is treated similarly to neuroblastoma (depending on the age and stage and risk assignment)? Thanks! I do not know how to add images (I am very slowly getting up to speed for editing, but plan to help here!)

DMLudwinski (talk) 15:48, 16 December 2007 (UTC)
 * First of all, let me commend you for your edits. You're learning quickly. Per the images: I'm not sure which image you're proposing to upload -- can you provide a URL? The image I added was from the German wiki page, so it was already in Wikimedia, and didn't need to be uploaded, just copied over to the English version. In most cases, works of the US government are public domain, but there are some exceptions (see Copyright status of work by the U.S. government, and Uploading images). You may also want to ask at Media copyright questions -- the users there specialize in these issues. --Arcadian (talk) 04:29, 19 December 2007 (UTC)

Thanks! I clicked on the image you added, and below the image the description states the source. I went to the cancer.gov source and did a search on neuroblastoma and found a photo of NB: neuroblastoma I think it public domain, but do not know how to add it to the NB article. Thanks for your help! DMLudwinski (talk) 19:35, 19 December 2007 (UTC)
 * I got it--I uploaded the neuroblastoma rosettes image from NCI and replaced the image of ganglioneuroblastoma which is wrongly labeled as "neuroblastoma.jpg" on the German wiki page. DMLudwinski (talk) 20:19, 20 December 2007 (UTC)
 * Nicely done. --Arcadian (talk) 22:30, 20 December 2007 (UTC)

GA review
I'll probably read through in detail tomorrow, but a first speed read suggests careful copyediting and checking for readability would be helpful. Just a quick read suggests MoS issues - eg ref numbers should follow punctuation with no space, and there are some places where glosses would help. The very last sentence, which looks odd, starting with a lower-case letter, would be much improved as "The protein p53...". There are places where a gloss for meaning might be helpful, esp if the phrase is a red-link. Jimfbleak (talk) 09:11, 30 December 2007 (UTC)

I'll do the formal review by Friday, please let me know if more time needed. Jimfbleak (talk) 08:11, 1 January 2008 (UTC) Much work to be done here! Thanks so much.208.123.11.69 (talk) 18:15, 1 January 2008 (UTC)
 * 1) ref numbers should follow punctuation with no space -I fixed several, not all. Ref 10 would be better at end of sentence
 * 2) Diagnosis- no refs for key first three paras
 * 3) Careful copyediting and checking for readability would be helpful. "Doesn't" is too informal, so is "this is how it works" "1980's" is wrong, should be "1980s". There may be others
 * 4) spell out y.o. for clarity
 * 5) gloss for multimodal therapy needed since the link is red and the meaning is not obvious
 * 6) The very last sentence, which looks odd, starting with a lower-case letter, would be much improved as "The protein p53...".
 * Thanks Jimfbleak for the great observations for the much needed editing improvements, and all the corrections made. Your attention is so appreciated! I have not tackled any copy-related improvements because there are so many significant high-risk treatment-related issues that could be added and referenced (although as a newbie I find doing references confusing!)
 * including the new COG phase III trial that opened 12/2007 to randomize single vs tandem transplant (will accrue 495),
 * and the studies leading up to this trial,
 * recently released preliminary results of phase III study (to purge or not to purge stem cells, closed spring 2006)
 * and the still-open phase III trial randomizing anti-GD2 antibody ch14.18 with cytokines with 13-cis-retinoic acid vs just 13cisRA,
 * the single-institution anti-GD2 antibody 3F8 used for the past 20 years at Memorial Sloan Kettering in New York
 * I would like to see the recent European trials included, especially the open German NB2004 and the open SIOPEN trial using a rapid COJEC chemotherapy regimen.


 * The items listed by Jimfbleak for the good article review have now (I believe) been addressed. --Arcadian (talk) 18:48, 1 January 2008 (UTC)
 * Per the items listed by 208.123.11.69 -- if you can bring PMIDs or URLs to this talk page, I would be happy to help in the reference formatting. --Arcadian (talk) 18:52, 1 January 2008 (UTC)
 * THANKS, will do! Having trouble with my login as well, now fixed I think. DMLudwinski (talk) 19:31, 1 January 2008 (UTC)

Current clinical trials (frontline therapy) for high-risk neuroblastoma
Thanks for the offer of help with references Arcadian. Below is an accumulation of information on clinical trials with external links. It may be too much and I have no problem with it being greatly simplified or ignored altogether. There is a little more to be said about efforts with anti-GD2 antibodies which I can add later. DMLudwinski (talk) 16:33, 2 January 2008 (UTC)

Currently there is no “standard” frontline treatment for high-risk neuroblastoma because the relapse rate is still unacceptably high. In an effort to improve survival rates for high-risk neuroblastoma, various therapies (clinical trials) are planned and carried out by cooperative groups as well as individual and small groups of institutions. Many patients are needed for phase III (randomized) trials to discern the effectiveness of new therapies. Worldwide incidence of high-risk NB is estimated to be 6,000 to 7,000 annually--compared to only 300-350 in the US-- so cooperative groups are often international.

A short history of phase III studies for high-risk neuroblastoma


 * 1991-1996: The first randomized (phase III) trial for 379 high-risk NB patients was carried out by the Children's Cancer Group (CCG-3891) http://www.ncbi.nlm.nih.gov/pubmed/10519894 which demonstrated improved survival with myeloablative therapy (with TBI) and 13-cis-retinoic acid (Accutane).
 * 1996-2003: The German (GPOH) study NB97 compared outcomes of 295 high-risk NB patients randomized for stem cell transplant or consolidation chemotherapy. Results showed increased survival with transplant. http://www.ncbi.nlm.nih.gov/pubmed/16129365?dopt=Abstract
 * 2000-2006: The recent study (COG-A3973) http://www.cancer.gov/templates/view_clinicaltrials.aspx?version=healthprofessional&cdrid=67429 questioned the need for purged stem cells for CEM-LI (carboplatin, etoposide, melphalan, with local irradiation) http://mmserver.cjp.com/gems/blood/ABMT.10.Villablanca.pdf transplant, began in 2000, and met the accrual goal of 486 in spring 2006. Purging stem cells was not found to improve survival (ref ASCO 2007 http://www.asco.org/ASCO/Abstracts+%26+Virtual+Meeting/Abstracts?&vmview=abst_detail_view&confID=47&abstractID=31659 ).
 * 2000-2012: An additional study (ANBL0032) http://www.cancer.gov/search/ViewClinicalTrials.aspx?cdrid=69018&version=HealthProfessional&protocolsearchid=2119048 will determine if the antibody ch14.18 with IL2 and GMSCF (studied retrospectively in German GPOH NB90 and NB 97 at a lower dose and without cytokines http://jco.ascopubs.org/cgi/content/full/22/17/3549 ) improves survival, and will accrue a total of 423 patients until 2012.
 * 2002-2008: SIOP (International Society of Paediatric Oncology) formed the European SIOP Neuroblastoma Group (ESIOP NB) in 1994 http://www.cure4kids.org/private/courses_documents/m_148/SIOP-2005-Education-Book.pdf (p 65) and activated a phase III high-risk NB protocol in 2002 (SIOP-EUROPE-HR-NBL-1) http://www.cancer.gov/search/ViewClinicalTrials.aspx?cdrid=69191&version=HealthProfessional&protocolsearchid=4015135 using “rapid” COJEC (8 cycles given at 10-day intervals) followed by transplant randomization to CEM (carboplatin, etoposide, melphalan) or BuMel (busulfan, melphalan) and then randomization to with or without ch14.18 antibody treatment. This study will evaluate the use of growth factors as well as compare transplant regimens, with or without ch14.18 antibody, and all patients receive retinoic acid. This trial will accrue 1000 patients (175 per year). There are eight arms to this study.
 * 2005-2010: The current German NB2004 http://www.kinderkrebsinfo.de/e1664/e1676/e1758/e7720/index_ger.html randomization will include MIBG therapy and randomize topotecan use in up-front therapy and will accrue a total of 642 for all risk groups (roughly half will be high-risk).
 * 2007-?: The COG phase III ANBL0532 http://www.cancer.gov/clinicaltrials/COG-ANBL0532 trial opened 12/2007 for accrual of 495 and will compare single vs tandem http://www.ncbi.nlm.nih.gov/pubmed/16782928 transplants, and induction begins with two cycles of topotecan.

Children's Oncology Group (COG) http://www.curesearch.org/resources/cog.aspx is the result of a merger http://jnci.oxfordjournals.org/cgi/content/full/92/23/1876 in 1999 with Children's Cancer Group (CCG) and Pediatric Oncology Group (POG), and currently has over 230 member institutions in the US, Canada, Australia, New Zealand, Netherlands, and Switzerland. COG is the largest pediatric cancer group, and 40,000 http://www.curesearch.org/our_research/index_sub.aspx?id=1523 children and young adults are currently treated on approximately 150 COG protocols. Requirements http://www.childrensoncologygroup.org/MiscellaneousPdf/3.1.1InstMmbrshp.pdf for membership as a COG institution and principal investigator include treating a minimum annual average of twelve newly diagnosed pediatric cancer cases. COG investigators must also enroll a minimum annual average of six children on COG therapeutic trials and a minimum of two children on non-therapeutic trials. Specific support http://www.childrensoncologygroup.org/MiscellaneousPdf/3.1.2ReqInstMmbrshp.pdf specialists and facilities must also be provided in COG institutions. Every pediatric oncology patient treated at COG hospitals must be registered in the COG database, even if they are not treated on a COG protocol.

A group of investigators specializing in neuroblastoma at 13 institutions comprise the New Approaches to Neuroblastoma Therapy http://www.nant.org (NANT) consortium. This group plans and offers phase I and phase II trials for refractory and relapsed neuroblastoma only (no frontline therapies).

The various study groups (COG, GPOH, E-SIOP, etc) each have protocols used to treat each risk group of neuroblastoma. Some COG institutions enroll patients on their own "in-house" trials. These are often called pilot studies, and occasionally include more than one institution. Memorial Sloan Kettering (MSK) http://www.mskcc.org/mskcc/html/62094.cfm, Children's Hospital of Philadelphia (CHOP) http://www.chop.edu/consumer/jsp/division/generic.jsp?id=77780 , Dana-Farber Cancer Institute (DFCI)/Boston Children's http://www.childrenshospital.org/az/Site1084/mainpageS1084P0.html , Chicago's Children's Memorial Hospital (CMH) http://www.childrensmemorial.org/depts/cancer/neuroblastoma1.aspx and St Jude’s http://www.stjude.org/stjude/v/index.jsp?vgnextoid=72df722d99f70110VgnVCM1000001e0215acRCRD&vgnextchannel=85e0bfe82e118010VgnVCM1000000e2015acRCRD are all notable examples of this. The institutional studies are possible because of the relatively large number of neuroblastoma cases they treat.

General rationale for current therapies--resources

Advances in the Diagnosis and Treatment of Neuroblastoma http://theoncologist.alphamedpress.org/cgi/content/full/8/3/278 Joanna L. Weinstein, Howard M. Katzenstein, Susan L. Cohn. The Oncologist, Vol. 8, No. 3, 278–292, June 2003

High-Risk Neuroblastoma: Beyond Intensification to Novel Therapy Approaches to Improve Outcome http://www.ipcr.us/dl/ASCO_ED_Neuroblastoma2005.pdf ASCO 2005 presentation by K. Matthay, CP Reynolds, R Versteeg

Risk-based Treatment for Children with Neuroblastoma http://www.cure4kids.org/private/courses_documents/m_148/DeBernardai_Bruno.pdf SIOP 2005 presentation by Bruno De Bernardi and Susan L. Cohn

Reduction From Seven to Five Cycles of Intensive Induction Chemotherapy in Children With High-Risk Neuroblastoma http://www.jco.org/cgi/content/full/22/24/4888 Brian H. Kushner, Kim Kramer, Michael P. LaQuaglia, Shakeel Modak, Karima Yataghene, Nai-Kong V. Cheung. Journal of Clinical Oncology, Vol 22, No 24 (December 15), 2004: pp. 4888-4892

ASCO 2007 presentations by S. Kreissman, J. Park, NK Cheung, J. Maris Pediatric Cancer I http://www.asco.org/portal/site/ASCO/menuitem.64cfbd0f85cb37b2eda2be0aee37a01d/?vgnextoid=09f8201eb61a7010VgnVCM100000ed730ad1RCRD&vmview=vm_session_presentations_view&index=y&confID=47&trackID=10&sessionID=394 and Education Session Recent Advances in Biology and Therapy http://www.asco.org/portal/site/ASCO/menuitem.64cfbd0f85cb37b2eda2be0aee37a01d/?vgnextoid=09f8201eb61a7010VgnVCM100000ed730ad1RCRD&vmview=vm_session_presentations_view&index=y&confID=47&trackID=10&sessionID=222

Neuroblastoma http://www.ncbi.nlm.nih.gov/pubmed/17586306?ordinalpos=4&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum John M Maris, Michael D Hogarty, Rochelle Bagatell, Susan L Cohn. Lancet, 369: 2106–20, June 23, 2007

Text reference:

Cheung NK and Cohn SL eds. Neuroblastoma. Springer: Berlin (2005)

DMLudwinski (talk) 16:33, 2 January 2008 (UTC)


 * I did notice the reference for #34 ^ "Painkiller Helps Against Child Cancer", medicalnewstoday.com, February 8, 2007, accessed March 8, 2007 (source apparently is a press release from the Karolinska Institutet in Sweden) didn't list the PMID http://www.ncbi.nlm.nih.gov/pubmed/17289900?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

DMLudwinski (talk) 18:19, 2 January 2008 (UTC)


 * One more thing! Opsoclonus myoclonus syndrome should be included under diagnosis or symptoms DMLudwinski (talk) 18:32, 2 January 2008 (UTC)

Good Article nomination

 * GA review (see here for criteria)


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 * a (prose): b (MoS):
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Chronology of relapse/refractory clinical trials
Pwallroth asked this question via email:


 * Would you have a problem with reorganizing the "Clinical trials for refractory and relapsed neuroblastoma" section so that the most recent treatments are first and the less recent are listed after?

Any thoughts? Since the other section (clinical trials for frontline therapy) is listed chronologically, I would think that section would also have to be rewritten in reverse chronological order.DMLudwinski (talk) 12:34, 17 June 2008 (UTC)

Help Find a Cure
The Childrens Neuroblastoma Cancer Foundation

There is hope.

http://www.nbhope.org/ —Preceding unsigned comment added by 70.235.188.214 (talk) 20:27, 14 August 2008 (UTC)

Also http://http://www.worldcommunitygrid.org/research/hfcc/overview.do - research that anyone with a PC can help with (and Mac, Linux, etc). Can this link be made part of the full article? There must be people reading the main article who'd love to know how they can help future generations? But I'll leave someone who knows more about Wikipedia than me to decide. —Preceding unsigned comment added by 80.175.12.57 (talk) 10:07, 22 January 2010 (UTC)

Refactory & Clinical Trials
The page doesn't explain what is meant by refactory neuroblastoma. I'm not a clinician, and haven't heard this use. If someone could clarify? I'm not sure whther sections 5.2 and 5.3 should be distinct? Perhaps they could be merged and cut down slightly? Perhaps restrict these sections to current trials rather than a history of neauroblastoma treatment. I think these parts are too long, and perhaps should be referenced for the very interested rather than included on a general page?

Ironick (talk) 09:49, 16 October 2008 (UTC)


 * Great points Ironick. I did wonder if the "history" of frontline treatments would be a bit much for the scope of this article. I will admit this is the only place on the web this collection can be found! (It took a LONG time to track down this history of treatments--and I agree, it is only of interest to those who want to know the evolution of current treatment--and to perhaps understand the controversy and question that remains in the minds of some ped oncologists who do not think NB should be treated with stem cell transplants). Where could we move it to-- a place for the more interested?


 * You also brought a up a great point about the unclear distinction between those two sections (5.2 and 5.3). The 5.2 covers frontline treatments for newly diagnosed cases of high-risk disease, and the second (5.3) covers treatment for those who do not respond adequately (refractory--disease remains in spite of intense frontline treatment--thus must be removed from frontline clinical trial) or relapsed NB--those who have a period of remission and then the disease recurs.


 * Relapse is very common in high-risk NB. At least 50% relapse after "successful" frontline treatment, and depending on the study reported-- 20% to 50% of all high-risk kids have refractory disease. These trials (for relapse and refractory) are of interest because if something works, it can be eventually incorporated into frontline treatment. DMLud (talk) 17:45, 29 October 2008 (UTC)

New Points April 2009
I removed 2 lines at the end of the introduction. No objection to reinclusion, but they should be cited. Especially the spontaneous regression part. I definately think the clinical trials for new treatments should be moved to a new page something like "Treatment of Neuroblastoma" and linked to other treatments etc. I also remember there being a history of treatment as well, which could be included there. I think this page should be a detailed introduction, I feel this information is too specific. Thoughts? Ironick (talk) 10:15, 29 April 2009 (UTC)
 * I agree that would be a great improvement. The article is too long and cumbersome as is--a separate treatment article would solve the problem! Are you up for the reorganizing Ironick? I don't know how to "start" a new article, and not sure how to create clear linkage and referencing between the two... DMLud (talk) 15:52, 29 April 2009 (UTC)

Review

 * 1) Does not follow WP:LEAD
 * 2) some issues with prose eg. "Its solid tumors, which take the form of a lump or mass, commonly begin in one of the adrenal glands, though they can also develop in nerve tissues in the neck, chest, abdomen, or pelvis."
 * 3) how frequent and what are the typical presentations need to be discussed
 * 4) no section on the history of this condition

-- Doc James (talk · contribs · email) 20:44, 9 June 2009 (UTC)
 * Thanks for the review--all items have been addressed (including some other updates and clean up) with the exception of the history--I found a couple of good resources and will add that ASAP. Thanks again for keeping the bar high! DMLud (talk) 22:41, 12 June 2009 (UTC)

Another issue


 * Not all the references are properly formatted. Came across about 10 or so that were not.


 * The lead should follow the format of the article. Currently the lead starts with epidemiology rather than symptoms. Doc James  (talk · contribs · email) 03:33, 2 September 2009 (UTC)

Incidence rates
The incidence rates quoted in the first sentence lack context. The number of cases per year should be given in per capita rather than absolute terms, especially since the statement is made that it is the most common cancer in infancy. 121.45.223.193 (talk) 12:12, 6 December 2013 (UTC)

External links modified
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Inaccurate Word
The word "baby" in this sentence is obviously not correct: "Occasionally it may be found in a baby by ultrasound during pregnancy." I tried to correct it to "fetus" instead, but got reverted. Someone else may want to fix this. SilverCobweb (talk) 23:18, 10 December 2016 (UTC)
 * Yes "baby" in the common usage of the word is correct. Doc James  (talk · contribs · email) 18:32, 11 December 2016 (UTC)


 * The sentence says it's during a pregnancy, so it's a fetus. The sentence should be corrected. SilverCobweb (talk) 02:09, 16 December 2016 (UTC)
 * It is appropriate to use common English much of the time. Doc James  (talk · contribs · email) 06:42, 16 December 2016 (UTC)

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