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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
eN
one
Oth
ers
CSO
M,
epip
hora
CSO
MSi
nusi
tisT
rism
usN
one
Non
eC
SOM
NA
,not
avai
labl
e;V
AC
/IE
,vin
cris
tine,
doxo
rubi
cin,
orac
tinom
ycin
-D,c
yclo
phos
pham
ide
alte
rnat
ing
with
ifos
fam
ide
and
etop
osid
e;PR
,par
tialr
espo
nse;
CR
,com
plet
ere
spon
se;I
CE
,ifo
sfam
ide,
carb
opla
tin,a
ndet
opos
ide;
LFU
,los
tto
follo
w-u
p;C
SOM
,Chr
onic
Supp
urat
ive
Otit
isM
edia
.
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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