Pediatr Blood Cancer 2011;56:477–481

BRIEF REPORTTherapy and Outcome of Primitive Neuroectodermal Tumor of the Jaw

Sameer Bakhshi, MD,1,* Subha Pathania, MD,1 B.K. Mohanti, MD,2 Sanjay Thulkar, MD,3 and Alok Thakar, MD4

Data pertaining to outcomes in jaw primitive neuroectodermaltumor (PNET) are lacking. Eleven cases of jaw PNET (five maxil-lary and six mandibular) were treated at our cancer center with thesame chemotherapeutic agents from June 2003 to January 2009. Fourpatients underwent surgery after neoadjuvant chemotherapy andall received local radiotherapy. At median follow-up of 56 months

(range: 19–77 months), 7/11 patients are in sustained remission.There was no difference in outcome with respect to site of tumor,and whether surgery was performed or not. These results support theuse of chemoradiation as initial modality of treatment rather thangoing for extensive and mutilating surgery. Pediatr Blood Cancer2011;56:477–481. © 2010 Wiley-Liss, Inc.

Key words: Ewing sarcoma; mandible; maxilla; primitive neuroectodermal tumor; therapy

INTRODUCTION

Primitive neuroectodermal tumor (PNET) or Ewing sarcoma isthe second most frequent primary malignant bone cancer. The mostfrequently affected sites are the long bones of the lower extremitiesand pelvis. Head and neck region accounts for 1–4% of all casesof PNET [1]. The most commonly affected bones in head and neckregion are jaw and skull bones [2]. However, data pertaining to thesesites with regard to outcomes using a uniform treatment modalityare lacking.

METHODS

This is a retrospective study of primary jaw PNET treated at ourcenter from June 2003 to January 2009. The patients’ demographicprofile, clinical data, metastatic workup, treatment, and survivalwere studied. Complete remission (CR), partial response (PR), andstable disease (SD) were defined as per RECIST criteria [3].

CLINICAL PROFILE

During the study period, there were 11 cases of primary jawPNET (six maxillary and five mandibular) with a median age of 16years (range 4–19 years) and male/female ratio of 9:2 (Table I). Allpatients presented with jaw swelling; one patient also had fever as apresenting manifestation (case #10). Diagnostic work-up includingbone marrow biopsy, bone scan, and computed tomography (CT)scan of chest did not reveal metastatic disease in any patient. CTscan of face showed variably enhancing mass lesion with hetero-geneous attenuation in all cases. There was bone destruction in allcases with tumor extension beyond the jaw in 8/11 cases. Periostealcalcification was noticed in one case only. All patients underwentbiopsy (two trucut and nine incisional) and histopathology revealeda small round malignant tumor which were positive for MIC-2 anti-gen. However, we did not have the means to study the reciprocalchromosomal translocation for this disease.

THERAPY AND OUTCOME

Chemotherapy was given using vincristine, doxorubicin, acti-nomycin D, cyclophosphamide, ifosfamide, and etoposide; threepatients (cases 1, 5, and 9) received these drugs as per the institu-tional protocol of St. Jude Children’s Research Hospital [4] while

the other patients received alternating cycles of the above drugs[5]. Repeat evaluation after 5–6 cycles of neoadjuvant chemother-apy revealed partial remission in all cases. All patients except case11 had residual soft tissue component on imaging after neoadju-vant chemotherapy. In only one of the patients (case 9), a biopsyof the soft tissue component was performed which showed fibro-collagenous tissue and so no surgery was performed on him. In5/9 remaining cases, the soft tissue component extended into sur-rounding structures such as inferior orbital wall and infratemporalfossa which would have resulted in mutilating surgery if a completeresection was attempted. Thus, a definitive surgery was performedin only four patients. One patient underwent partial maxillectomy;one total maxillectomy; one marginal mandiblectomy; and one totalmandiblectomy. Out of these four patients, histopathological exam-ination showed evidence of active tumor in all and in one of thesepatients (case 6), the tumor was involving the posterior margin aswell.

Radiotherapy was given in all patients irrespective of surgeryat a dose of 45–55 Gy (median 50 Gy) in 20–30 fractions (median25 fractions) 5 days a week, over 5–6 weeks. Following radiother-apy and/or surgery, further chemotherapy was given in all casesas per protocol for 48 weeks. One of the patients (case 8) devel-oped a chronic discharging sinus at the surgical site due to radiationnecrosis of the mandible and required excision of the affected bonefragment. Seven of 11 cases are in CR at a median follow-upof 56 months (range: 19–77) since diagnosis. The 3-year event-free survival (EFS) is 59 ± 15% at a median follow-up of 24.6months (Fig. 1). The 3-year EFS of patients with mandibular PNET

1Department of Medical Oncology, All India Institute of Medical Sci-ences, New Delhi, India; 2Department of Radiotherapy, Dr B.R.A.Institute Rotary Cancer Hospital, All India Institute of Medical Sci-ences, New Delhi, India; 3Department of Radiology, Dr B.R.A. InstituteRotary Cancer Hospital, All India Institute of Medical Sciences, NewDelhi, India; 4Department of Otorhinolaryngiology, Dr B.R.A. InstituteRotary Cancer Hospital, All India Institute of Medical Sciences, NewDelhi, India

Conflict of interest: Nothing to declare.

*Correspondence to: Sameer Bakhshi, Associate Professor of PediatricOncology, Department of Medical Oncology, Dr B.R.A. Institute RotaryCancer Hospital, All India Institute of Medical Sciences, New Delhi,India. E-mail: sambakh@hotmail.com

Received 15 February 2010; Accepted 5 April 2010

© 2010 Wiley-Liss, Inc.DOI 10.1002/pbc.22615Published online 11 November 2010 in Wiley Online Library(wileyonlinelibrary.com).

478 Bakhshi et al.

TABLE

I.Detai

lsof

Pre

sent

atio

n,The

rapy

,and

Out

com

eof

Pat

ient

sW

ith

Jaw

PNET

Cas

e#1

Cas

e#2

Cas

e#3

Cas

e#4

Cas

e#5

Cas

e#6

Cas

e#7

Cas

e#8

Cas

e#9

Cas

e#1

0C

ase

#11

Age

/sex

4ye

ars/

F13

year

s/F

7ye

ars/

M7

year

s/M

7ye

ars/

M16 ye

ars/

M13 ye

ars/

M19 ye

ars/

M19 ye

ars/

M12 ye

ars/

M11 ye

ars/

MC

hief

com

-pl

aint

s

Swel

ling

and

pain

Swel

ling

Swel

ling

and

pain

Swel

ling

and

pain

Swel

ling

and

pain

Swel

ling

and

pain

Swel

ling,

pain

,and

epis

taxi

s

Swel

ling

and

pain

Swel

ling

and

pain

Swel

ling,

pain

,and

feve

r

Pain

Dur

atio

nof sy

mpt

oms

2.5

mon

ths

3m

onth

s3

mon

ths

2m

onth

s4.

5m

onth

s3

mon

ths

3.5

mon

ths

1.5

mon

ths

2.5

mon

ths

6m

onth

s3

mon

ths

Site

Max

illa

Max

illa

Max

illa

Max

illa

Max

illa

Man

dibl

eM

andi

ble

Man

dibl

eM

andi

ble

Man

dibl

eM

andi

ble

Imag

ing

(CT

scan

)T

umor

size

9cm

5cm

9cm

6cm

9cm

NA

8cm

NA

9cm

8cm

8cm

Bon

ede

stru

c-tio

n

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Cal

cifi-

catio

nN

oN

oN

oN

oN

oN

oN

oN

oN

oY

esN

o

Surg

ery

Part

ial

max

illec

-to

my

Not

done

Not

done

Not

done

Tota

lm

axill

ec-

tom

y

Mar

gina

lm

andi

blec

-to

my

Not

done

Rig

htm

andi

blec

-to

my

Not

done

Not

done

Not

done

Rad

ioth

erap

y45

Gy/

25Fr

55G

y/30

Fr50

Gy/

25Fr

55G

y/30

Fr55

Gy/

30Fr

50.6

Gy/

27Fr

55G

y/30

Fr50

Gy/

20Fr

55G

y/25

Fr55

Gy/

28Fr

55G

y/30

Fr

Mid

eval

uatio

nPR

PRPR

PRPR

PRPR

PRPR

PRPR

End

eval

uatio

nC

RC

RPr

ogre

ssio

non

ther

apy

CR

CR

Prog

ress

ion

onth

erap

ySt

illon

ther

apy

CR

CR

Die

dof

chem

o-to

xici

tyat

wee

k39

ofch

emot

her-

apy

CR

Pediatr Blood Cancer DOI 10.1002/pbc

Primitive Neuroectodermal Tumor of Jaw 479

TABLE

I.(C

ontinu

ed)

Cas

e#1

Cas

e#2

Cas

e#3

Cas

e#4

Cas

e#5

Cas

e#6

Cas

e#7

Cas

e#8

Cas

e#9

Cas

e#1

0C

ase

#11

Follo

w-u

pC

Rat

75m

onth

sL

ocal

prog

ress

ion

18m

onth

saf

ter

diag

nosi

s.Sh

ew

astr

eate

dw

ithsa

lvag

eIC

Ech

emot

hera

pybu

tdie

dat

25m

onth

sfr

omdi

agno

sis

Prog

ress

ion

11m

onth

saf

ter

diag

nosi

s.N

osa

lvag

ech

emot

her-

apy

take

nan

dw

asth

enL

FU

CR

at19

mon

ths

CR

at77

mon

ths

Prog

ress

ion

8m

onth

saf

ter

diag

nosi

s.N

osa

lvag

ech

emot

her-

apy

take

nan

dw

asth

enL

FU

CR

at12

mon

ths

CR

at40

mon

ths

CR

at72

mon

ths

Dea

th17

mon

ths

afte

rdi

agno

sis

CR

at37

mon

ths

Lat

eef

fect

sFa

cial

disfi

gure

men

tN

one

Not

appl

icab

leN

otap

plic

able

No

Pres

ent

Not

appl

icab

leN

one

Pres

ent

Non

eN

otap

plic

able

Non

e

Den

titio

nIr

regu

lar

erup

tion

Irre

gula

rer

uptio

nIr

regu

lar

erup

tion

Non

eL

oss

ofte

eth;

now

havi

ngar

tifici

alde

ntur

e

Non

eN

one

Dif

ficul

tyin

swal

low

ingN

one

Pres

ent

(for

solid

s)

No

Non

ePr

esen

t(f

orso

lids)

Non

eN

one

Spee

chN

one

Non

eD

ysar

thri

aw

ithna

sal

twan

g

Non

eN

one

Non

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one

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ers

CSO

M,

epip

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CSO

MSi

nusi

tisT

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usN

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NA

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avai

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AC

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rubi

cin,

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alte

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with

ifos

fam

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and

etop

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,par

tialr

espo

nse;

CR

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plet

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spon

se;I

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,ifo

sfam

ide,

carb

opla

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.

Pediatr Blood Cancer DOI 10.1002/pbc

480 Bakhshi et al.

Fig. 1. Overall EFS of the patients with jaw PNET at 3 years is 59 ± 15% (A); EFS of maxillary PNET is 53.3 ± 24% versus 62.5 ± 21% formandibular PNET (B); and EFS of jaw PNET with surgery is 75 ± 21% and 45.7 ± 22% without surgical resection (C).

is 62.5 ± 21% as compared to 53.3 ± 24% for maxillary PNET(P = 0.96) (Fig. 1B). Further, 3-year EFS of patients who under-went surgery was 75 ± 21% as compared to 45.7 ± 22% for thosewho did not undergo surgery (P = 0.58) (Fig. 1C). Two of the fourpatients who underwent surgery have significant facial disfigure-ment and are planned for facial reconstructive surgery; further, theyalso have significant problems in dentition and speech (Table I).

DISCUSSION

Jaw PNET is a rare tumor with most previous reports beingsingle cases or small series [6–8]. Imaging findings in PNET suggestpresence of large, infiltrative, poorly circumscribed masses withheterogeneous attenuation and variable contrast enhancement [9].Calcification is unusual with no calcification being observed in anyof the reported cases of jaw PNET while in our series small calcificdensities was observed in one case. On follow-up, imaging revealedsclerosis and cortex formation in five cases.

The reported rate of metastasis in PNET is approximately 20–25% [5]. At our institute, almost half of our cases of PNET aremetastatic at presentation, possibly because of a referral bias anddelayed presentation. However, none of our cases of primary jawPNET had systemic metastasis despite extension beyond the jawin 8/11 cases. It appears that the rate of metastasis is lesser in jawPNET as compared to PNET at other sites. A similar observationwas also made in orbital PNET wherein despite large tumors, noneof the cases had distant metastases [10].

Most of the case reports have focused on pathological diagnosis,radiological presentations, and surgical aspects [11–15]. The caseseries have included all sarcomas of head and neck region with jawPNET being a small fraction of the sarcomas [16,17]; there is noseparate analysis for jaw PNET. Further, these series have includedpatients over 2–4 decades, during which time varying chemotherapyregimens have been used [18]; thus, it becomes difficult to make anassessment of outcomes in PNET in this rare site. In all our casesover last 6 years, local therapy in the form of radiotherapy with orwithout surgery was given after neoadjuvant chemotherapy and thenfollowed by adjuvant chemotherapy. With this therapeutic protocol,7 out of 11 cases achieved sustained remission. We were not able toshow if surgery is always mandatory or not because of small patient

numbers. In regions where patients may present in advanced stages,we feel that chemoradiation may be used as the initial modalityof treatment as in orbital rhabdomyosarcoma rather than going forextensive and mutilating surgery straightaway. In smaller tumorssurgery may be done upfront.

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