Neuroblastoma

Meg Browning

3/31/04

Epidemiology

6% of childhood malignanciesMost common cancer in children < 1 y.o.2/3 are in children < 5 y.o.70% of all patients have mets at dxOne of the small blue round cell tumors

[leukemia, lymphoma, Ewing/PNET, RMS, Wilms, desmoplastic]

Clinical findings

Originates in sympathetic NS: paraspinal ganglia or adrenal medulla

Most common: mass effect sxs, bone pain, proptosis/periorbital ecchymoses from retrobulbar mets

Can invade neural foramina, paralysisLess commonly: fever, anemia, HTNRarely: VIP secretion diarrhea, cerebellar

ataxia, opsoclonus/myoclonus

Prognostic factors

Stage (males present later, but o/w male is not worse)

Age (<1 y.o. better except maybe <6 wks with no skin nodules)

Primary tumor site ONLY for stage 3-4 (abd is worse)

+/- Primary tumor size (> 100 cm3 is worse)

Shimada criteria

Prognostic factors, cont.

Biology, esp. myc-n but also:Good: hyperdiploidy, TRK-A (high-affinity

nerve growth factor receptor, proto-oncogene), LNGFR, HA-ras p 21

Bad: 1p-, 17/17q-, B-myb oncogene, increased telomerase RNA (hTR), high ferritin, neuron-specific enolase, high LDH, low tumor CD44

NOT catecholamine levels

ShimadaFavorable Unfavorable

Age > 5yAge <1.5y

Stroma rich

Nodular pattern? yesno

Stroma poor

Age <1.5yyes no

MKI < 200? DifferentiatedAND MKI < 200?

yesno

yes no

Staging (INSS)

1: localized, GTR, attached +LN’s okay2A: as above but no GTR2B: ipsilateral +LN’s: must Bx contralat LN’s3: Unresectable tumor crossing midline (edge

of vertebral body) +/- regional nodes

OR bilateral extension/nodes (regional only)• 4: Disseminated tumor, not 4S• 4S: Stage 1, 2A, or 2B primary with mets ONLY

to skin, liver, and/or < 10% of marrow; MIBG (-) if done

Work-up is therefore:

MIBG or bone scanCT/MR to look for nodes and evaluate liverCXRCatecholamines Tumor biology, at least for myc-n and ploidyBMA and BxPath on any relevant nodes (if not already

stage 4)

Treatment and Prognosis1: > 90%, still good even with local

recurrence. Surgery only UNLESS: age > 2y, myc-n amplified, unfavorable histology, ? +LN

2: 75-90%. Bx/surg, chemo (4-6 mos of CTX/DOX), then definitive surg.

3, <1y: 80%. Surg +/- chemo3, >1y: 50-70%. Surg + chemo, +/-

XRT. May need SCT if myc-n amplified.

Rx and Px, cont.4, <1y: 50-80%, avg. 60%; biology

important (approaches 0 if myc-n; approaches 95% without)

4, >1y: 10-40%, avg. 15%*; SCT better than chemo alone

4S: 57-100%, better if no sxsRecurrent Dz: bad if disseminated;

usually disseminated. CNS involvement common, UNLIKE at primary Dx.

*this is pre- the new protocol, which we’ll take on next

COG A3973Purged v. Unpurged PBSCT for NBL

6 3-week cycles of chemo1, 2, 4, and 6 VCR/CTX/DOX (+MESNA & G)3 & 5 VP/CISPL (+ GCSF)

Harvest after cycle 2 (Goes to LA; rules are complex. HD-GCSF is used for that cycle, on a specific schedule. Purging is randomized and has a separate consent.

Assessment of remission is also done at that time; + marrow, progressive dz, HIV+, and pregnant pt’s do not go on to SCT; there is a chemo maintenance arm.

Surgery after cycle 5

COG A3973: more on SCTPt’s in CR, VGPR, and PR with an adequate

(5 x 106 CD34+ cells/kg) tumor-free harvest product go on to SCT.

Pt’s with minimal response may come off or stay on.

There is a biology study re tumor detection, and another biology research part (the latter requires initials!)

Conditioning (“consolidation”) for SCT is with CARBO/MEL/VP (+ G). Dosing is based on nuc med GFR, which must be done before MIBG!

Further RxQOL study requires separate initials+/- XRT 1 mo after SCT to primary site and any

mets “w/o significant response to chemo.”cis-Retinoic acid: new randomization; new

consent. 6 mos of r.a. +/- anti-GD2 & GM-CSF & IL-2. Starts 2 mo after SCT.

Pt’s ineligible for SCT get 3 cycles of CYCLO/TOPO, and may still go on to XRT and/or r.a.

Recommendations for supportive care during SCT are c/w what we do for an allo transplant.

Subject of debate:When to involve BMT?

We as a group (Onc/BMT) need to develop a plan that is satisfactory to all and helps our solid tumor/autoBMT patients transition successfully back and forth between the two teams.

For the foreseeable future, the BMT team is still going to handle the auto-transplants – it’s required for BMT program accreditation.

Suggestions?

Summary

Common as pediatric solid tumors goExcellent Px in infants without myc-n

amplificationCurrent Px on the new high-risk protocol is

generally being quoted around 30-40%Incredibly variable clinical course, largely

based on tumor biology, has made this an attractive tumor to study – look for a “vaccine” protocol to come down the pike in the next few years.