Age-Based Treatment of Aggressive Fibromatosis in the Head and Neck Region

PATHOLOGY

Fou

Ch

Un

Mil

Fou

Fou

Mil

Ma

Sto

Age-Based Treatment of AggressiveFibromatosis in the Head and Neck Region

*Senior

rth Mi

ina.

yResideiversity

zSenioritary M

xAssocirthMil

jjSeniorrthMil

{Profesitary M

#Profes

xillofac

matolog

Weiqi Wang, MD,* Ujjwal Koirala, MDS,y Shufang Ma, MD,z Guicai Liu, PhD, MD,xMingchao Ding, MD,jj Xiaoguang Hu, PhD, MD,{ and Delin Lei, PhD, MD#

Purpose: To review our experience regarding the difference in management and treatment outcomes of

aggressive fibromatosis of the head and neck region in children and adults, emphasizing, in particular, the

role of conservative surgery in comprehensive treatment strategies.

Patients andMethods: A retrospective analysis of patients with aggressive fibromatosis was performed

during a 5-year period (2008 to 2012). Nine patients were enrolled in the present study, including 5

children (age, <18 years) and 4 adults (age, >18 years). All patients underwent surgical intervention and

were treated by surgical resection with different surgical margins. Adjuvant low-dose chemotherapy

and radiotherapy were given to pediatric and adult patients, respectively, with macroscopically or micro-

scopically positive surgical margins.

Results: All 5 pediatric patients (3 females and 2 males) received low-dose chemotherapy after

conservative surgical resection (in 4 patients, microscopically incomplete resection; and in 1 patient, mac-

roscopic residual tumor). Of the 4 adults (3 females and 1 male), 2 underwent complete surgical resectionand 2 underwent surgery and postoperative radiotherapy (1 patient had microscopically suspected resid-

ual tumor and 1 had macroscopic residual tumor). The patients were followed up for a period of 7 to 51

months. Two pediatric patients and one adult patient had disease progression after resection and became

stable after continued adjuvant therapy. None of the patients had functional or cosmetic defects. All

patients had good long-term outcomes, with no disease progression.

Conclusions: For the treatment of aggressive fibromatosis, conservative resection with preservation of

form and function should be given greater priority in all age groups. Also, postoperative adjuvant therapy is

vital for patients with gross or microscopic residual tumor to obtain progression-free survival.

� 2014Published by Elsevier Inc onbehalfof theAmericanAssociationofOral andMaxillofacial Surgeons

J Oral Maxillofac Surg 72:311-321, 2014

Aggressive fibromatosis (AF), also known as desmoid

tumor or musculoaponeurotic fibromatosis, is rare.It is a histologically benign, deep-seated monoclonal

Resident, Department of Oral and Maxillofacial Surgery,

litary Medical University School of Stomatology, Xi’an,

nt, Department of Oral and Maxillofacial Surgery, Jiamusi

School of Stomatology, Jiamusi, China.

Resident, Department of Pediatric Dentistry, Fourth

edical University School of Stomatology, Xi-an, China.

ate Professor, Department of Oral and Maxillofacial Surgery,

itaryMedical University School of Stomatology, Xi’an, China.

Resident, Department of Oral and Maxillofacial Surgery,

itaryMedical University School of Stomatology, Xi’an, China.

sor, Department of Oral and Maxillofacial Surgery, Fourth

edical University School of Stomatology, Xi’an, China.

sor, Head of Department, Department of Oral and

ial Surgery, Fourth Military Medical University School of

y, Xi’an, China.

311

myofibroblastic neoplasm that originates from muscu-

loaponeurotic stromal structures and displays locallyaggressive growth. The incidence of AF is 2 to 4 per

Drs Wang, Koirala, and Ma contributed equally to the present

study.

Conflict of Interest Disclosures: None of the authors reported any

disclosures.

Address correspondence and reprint requests to Dr Hu:

Department of Oral and Maxillofacial Surgery, Fourth Military Medi-

cal University School of Stomatology, 145 Chang Le Xi Road, Xi’an

710032, China; e-mail: [email protected]

Received June 27 2013

Accepted July 23 2013

� 2014 Published by Elsevier Inc on behalf of the American Association of Oral

and Maxillofacial Surgeons

0278-2391/13/00928-2$36.00/0

http://dx.doi.org/10.1016/j.joms.2013.07.021

Delta:1_given name

Delta:1_surname

Delta:1_given name

Delta:1_surname

Delta:1_given name

Delta:1_surname

Delta:1_given name

mailto:[email protected]

http://dx.doi.org/10.1016/j.joms.2013.07.021

312 AGE-BASED TREATMENT OF AF

1 million population annually, with a female/male

ratio of 3:1. The incidence of AF in children peaks

at about 8 years of age (range, birth to 19 years).1 In

adults, AF peaks in the third and fourth decades.2-4

The age distribution profile has demonstrated 4

distinct peak periods: the juvenile period, fertile

period, middle-age period, and old-age period.5 Head

and neck lesions appear to infiltrate more aggressivelyand to grow more rapidly than lesions arising in other

locations.4,6

The pathogenesis of AF is most likely multifactorial.

A genetic predisposition,7 endocrine factors,2 and

trauma,8 including surgical trauma,9 play some role

in the etiology of these lesions. The incidence is

greater in families with familial AF, familial adenoma-

tous polyposis, and Gardner syndrome.10 Recently,AF was reported to derive from the mesenchymal pro-

genitor cells, and wound healing is believed to play

a crucial role in its etiopathogenesis.11,12

Surgical resectionwithnegativemargins has been con-

sidered the reference standard of treatment. Complete

surgical excision can produce deleterious alterations of

the facial framework, resulting in esthetic and functional

deficits. These alterations will be apparent and shouldnot be ignored. Thus, conservative resection with addi-

tional systemic therapy is indicated for patients with an

unresectable tumor.13-16 Nonsurgical treatment, such as

radiotherapy,17-19 chemotherapy, imatinib therapy,20,21

hormonal therapy, and nonsteroidal anti-inflammatory

drugs,21 have also been used as primary therapy or adju-

vant treatment to surgery, with variable results.

In the present study, we have described a series of9 cases of AF and discussed the clinical behavior, radio-

graphic features, treatment modalities at different

ages, and response to treatment, focused particularly

on the role of conservative surgery.

Table 1. SUMMARY OF PRESENTATION AND DIAGNOSIS

Pt. No. Age (yr) Gender

Duration of

Tumor Mass (mo) Tumor Size (c

1 17 Female 1 5.8 � 3.2 � 3

2 34 Male 36 0.8 � 1.3 � 1

3 3 Female 1 3.3 � 3.4 � 4

4 49 Female 5 2.0 � 1.2 � 1

5 20 Female 17 7.5 � 6.5 � 3

6 17 Male 48 2.1 � 1.3 � 1

7 1 Male 3 3.5 � 4.0 � 2

8 13 Female 1 4.0 � 3.5 � 2

9 39 Female 1 9.0 � 3.0 � 3

Abbreviation: Pt. No., patient number.

Wang et al. Age-Based Treatment of AF. J Oral Maxillofac Surg 2014.

Patients and Methods

A retrospective chart reviewwas performed to iden-

tify all patients with a diagnosis of AF of the head and

neck region treated at the Department of Oral and

Maxillofacial Surgery, Fourth Military Medical Univer-

sity School of Stomatology from January 1, 2008 to

December 31, 2012. The patients were identified

from the institutional pathology database. A senior pa-thologist reviewed the original histopathologic reports

and tumor specimens to confirm the diagnosis of AF.

The clinical data of all the patientswere retrospectively

reviewed, including patient characteristics, signs and

symptoms at the presentation, diagnostic methods,

treatment modalities, and treatment outcome. Our in-

stitutional review board approved the present study,

and all patients or their guardians provided written in-formed consent for enrollment in the present study.

The lesions were located in the submandibular re-

gion in 2 patients, the neck in 2 patients, the right para-

pharyngeal area up to the skull base in 1 patient, the

maxilla in 1 patient, the zygoma in 1 patient, the in-

fraorbital region in 1 patient, and parotid gland in 1 pa-

tient (Table 1). All the patients underwent surgical

resection. After surgical resection, the lesions werecategorized as either a clear negative margin or a posi-

tive margin with the help of frozen section analysis.

When the invasive tumor front was 5 mm or more

from the resected margin, it was considered a clear

margin. When carcinoma in situ or invasive carcinoma

was present at the margin of resection, it was consid-

ered a positive margin. The positive margins were con-

sidered macroscopic positive margins if the remainingtumor front could be palpated or seen grossly or mi-

croscopic positive margins if the tumor cells could

be detected only by frozen section analysis.

m) Presentation Pain

.7 Swelling on right side of neck No

.4 Swelling on right malar region No

.5 Dysphagia with lesion on right parapharyngeal

area

No

.1 Swelling on right infraorbital region No

.9 Torticollis, pain and neck mass Yes

.9 Swelling on right side of face accompanied by

ipsilateral facial nerve weakness

No

.2 Swelling on left submandibular region No

.5 Malocclusion No

.3 Swelling on left submandibular region with

slowly increasing trismus

No

FIGURE 1. A, Preoperative, B, intraoperative, and C, macro-scopic appearance of aggressive fibromatosis in submandibularregion of patient 3. Note, the lingual cortex has been resected,preserving the continuity of the mandible. Macroscopically, whitecollagenized bands and irregular spiculated margins can beseen.

Wang et al. Age-Based Treatment of AF. J Oral Maxillofac Surg

2014.

WANG ET AL 313

The tumors were classified as resectable or nonre-

sectable on the basis of the functional and cosmetic

effect. If a clear margin could be obtained only by

aggressive resection of vital structures such as major

blood vessels, nerves, and muscles of the neck or by

segmental resection of jaws, leading to impaired

growth, function, and esthetics, these tumors were

considered unresectable, and a conservative surgicalapproach was used. When the mandible, maxilla,

and infraorbital rim were involved, depending on the

tumor extent, the periosteum only, or a part of the cor-

tex plus the periosteum, was resected, preserving the

bones’ integrity, which is vital for facial development,

function, and esthetics (Fig 1). For lesions involving

the muscles of the neck, only the infiltrated muscle

was resected, either partly or completely, preservingthe nearby vital structures such as the spinal accessory

nerve and carotid arteries (Fig 2). All pediatric patients

who had microscopically or macroscopically residual

tumor underwent low-dose chemotherapy with intra-

venous methotrexate (MTX; 30 mg/m2) plus vinblas-

tine (VBL; 5 mg/m2) every week for 26 weeks. The

regimen was then administered on alternate weeks

for the next 26 weeks. The chemotherapy was started6 weeks postoperatively. For the adults with micro-

scopic or macroscopic residual disease, adjuvant ra-

diotherapy at a rate of 1.8 Gy/day for 5 days/wk to

a total dose of 55 Gy, was given to control disease pro-

gression and prevent recurrence.

Adjuvant low-dose chemotherapy (MTX and VBL)

was selected for pediatric patients, because, first, AF

in head and neck region in the pediatric age group ismore aggressive and has a greater tendency to reoccur.

Second, radiation doses greater than the 50 Gy re-

quired for tumor control can lead to growth problems

and a long-term risk of secondary malignancy.1,22

Third, radiotherapy has appeared to be less effective

treatment of AF in children18 and has resulted in poor

locoregional control.23 Fourth, VBL and MTX in low

doses have been shown to control progression of pedi-atric AF24,25 and to play amajor role in inducing growth

arrest and tumor stabilization in slowly evolving

pediatric AF.26 Finally, this combination is safe27 and

has promise for long-term disease control.28

The follow-up examinations were done clinically

and using ultrasonography, magnetic resonance im-

aging (MRI), or computed tomography (CT) every

3 months for the first year, every 6 months for thenext 2 years, and every 12 months thereafter. The

response to therapy was defined as complete remis-

sion if the disease had disappeared completely;

partial remission when the tumor reduction greater

than 50% of the greatest tumor dimension was

achieved; a minor response when the maximal

tumor reduction was greater than 25% but less

than 50%; stable disease when the maximal tumor

FIGURE 2. A, Preoperative clinical appearance of the mass on the left side of the neck in patient 5, and, B, intraoperative view after resectionof internal jugular vein and sternocleidomastoid muscle, along with the tumor-preserving spinal accessory nerve. C,Macroscopic appearanceof tumor demonstrating a white, fibrotic mass. D, View at 2 years postoperatively.



reduction was less than 25% or when no tumorshrinkage occurred after chemotherapy; and disease

progression if the tumor had increased in size

greater than 25% or new biopsy-proven lesions

were detected. In children, in particular, ultrasonog-

raphy or magnetic resonance imaging was preferred

to CT for the follow-up studies to prevent unneces-

sary radiation unless bone was involved.

The patients were evaluated from their histologicdiagnosis to their latest uneventful follow-up examina-

tion or disease progression, recurrence, or death. The

follow-up period ranged from 7 to 51 months

(mean, 24.4).

PATIENT CHARACTERISTICS AND SYMPTOMS ATPRESENTATION

Of the 9 patients, 6 were female and 3 were male,

ranging in age from 1 to 49 years (mean, 21.6). Five pa-

tients were children, and four were adults. None had

Gardner syndrome. The duration of symptoms ranged

from 1 week to 4 years, with painless swelling themost common symptom.

All patients presented with local swelling; 2 patients

had slowly developed trismus and malocclusion

(patients 8 and 9) before obvious external swelling.

One patient presented with dysphagia as a secondary

symptom to the swelling (patient 3). The tumor was

found to involve the skull base and parapharyngeal

area. Only 1 patient presented with pain (patient 5)that involved the sternomastoid muscle and internal

jugular vein. Patient 6 presented with facial swelling

and a 3-month history of facial nerve weakness. The

presentation and diagnosis of the individual cases

have been summarized in Table 2.

IMAGING CHARACTERISTICS

MRI remains the modality of choice for the assess-

ment of the nature and size of the soft tissue lesion

and involvement of surrounding structures. MRI

will show a characteristic nonspecific homogenous

Table 2. SUMMARY OF MANAGEMENT AND TREATMENT OUTCOME

Pt.

No.

Age

(yr) Gender Region

Primary

Treatment

Residual

Disease

Adjuvant

Therapy

Progression

After

Primary

Treatment Recurrence

Outcome

(Follow-Up)

1 17 Female Right side of neck MIR PM ChT Yes Yes Recurrence at

2mo treated

with low-

dose ChT,

SD (36 mo)

2 34 Male Right malar

region

CR NM No No No SD (51 mo)

3 3 Female Right

parapharyngeal

region up to

skull base

MIR PM ChT No No CR (27 mo)

4 49 Female Right infraorbital

region

CR NM No No No CR (33 mo)

5 20 Female Left side of neck CR PM RT No No CR (25 mo)

6 17 Male Left parotid gland

region


7 1 Male Left suprahyoid

muscles

PR Macroscopic ChT Yes No SD (18 mo)

8 13 Female Left maxillary

region


9 39 Female Left suprahyoid,

masseter, and

medial

ptyerygoid

muscles

PR Macroscopic RT Yes No Morbidity

from

adjunct

treatment;

very poor

mouth

opening;

MR (7 mo)

Abbreviations: ChT, chemotherapy; CR, complete remission; MIR, microscopically incomplete resection; MR, minor response;NM, negative margin; PM, positive margin; PR, partial resection; Pt. No., patient number; RT, radiotherapy; SD, stable disease for>3 months.


WANG ET AL 315

isointensity or mild hypointensity signal, representing

highly collagenized tissue on T1-weighted imaging. Fi-

bromatoses with less collagen and more cellularity will

show a heterogeneous, nonspecific, high-signal inten-sityonT2-weighted imaging(Fig3A).CTwill showanon-

specific soft tissue mass, with a similar attenuation to

that of the surrounding muscles and pressure erosion

of the adjacent bone (Fig 3B). Doppler ultrasonography

will reveal a heterogeneous hypoechogenicity and in-

creased surrounding vascularity (Fig 3C).

PATHOLOGY RESULTS

Microscopic examination of the tumor disclosed his-

tologic features of AF. The tumor was composed of

bland-like spindle cells and inconspicuous nucleoli

(Fig 4) andwas characterized by abundant collagen be-

tween the tumor cells. No atypical mitosis or anaplas-

tic elements were seen.

Results

Of the 5 children, 4 had a microscopically incom-plete resection and 1 (patient 7), with a deeply infiltra-

tive tumor in the suprahyoid groups of muscles, had

macroscopic residual tumor. All 5 patients received

low-dose chemotherapy after conservative tumor re-

section. Three patients (patients 1, 3, and 7) experi-

enced mild nausea and vomiting. Patient 1 had

moderate neutropenia (grade III), 750 cells/mL after

10 doses. The level had increased to normal aftermissing 2 doses andwas not associated with infection;

however, the patient did not want to continue chemo-

therapy, and it was terminated. Two months later, the

same patient (patient 1) developed local recurrence.

FIGURE 3. A, T2-weighted magnetic resonance imaging scan of aggressive fibromatosis on the neck showing heterogeneous high-signal in-tensity with infiltrative margins in patient 5. B, Computed tomography scan of patient 3 showing nonspecific, soft tissue mass infiltrating intosurrounding muscles and fascial plane and extending up to the base of the skull and causing erosion of the mandibular ramus. (Fig 3 contin-ued on next page.)



The chemotherapy was restarted and completed un-

eventfully, achieving disease stabilization. Patient 7

developed disease progression during chemotherapy

(after 3 months) and was treated with continued

low-dose chemotherapy and showed no additional

tumor growth on MRI 18 months later. The other

3 patients did not demonstrate tumor recurrence clin-

ically or radiographically during their follow-

up period.

Of the 4 adults, 2 patients (patients 2 and 4)

achieved complete excision with negative surgical

margins. Complete surgical resection was not possible

FIGURE 3 (cont’d). C, Color Doppler ultrasound scan of patient 3 demonstrating area of heterogeneous hypoechogenicity and increasedvascularity.


WANG ET AL 317

in patients 5 and 9 because of involvement of the

suprahyoid muscles and underwent adjunct

radiotherapy after conservative surgery. Patient 9 had

macroscopic residual tumor, and radiotherapy did

not cause significant tumor regression, although a ces-sation of progressive diseasewas found.Within this pa-

tient, the tumor had remained quiescent until the last

follow-up visit (7 months); however, the previously

present trismus had increased, further limiting the

mouth opening to 14 mm only. No recurrence was

seen in any of the 4 adult patients. The management

and treatment outcomes of the individual patients

are summarized in Table 2.

Discussion

Despite their nonmetastatic nature, desmoid tumors

have been classified by the World Health Organization

as intermediate grade tumors because of their propen-

sity for locally invasive growth and a tendency toward

local recurrence, leading to considerable morbidity

and, in rare circumstances, death.29 AF is a rare benign

tumor accounting for approximately 0.03% of all neo-plasms and 3% of all soft tissue tumors. Of the extra-

abdominal fibromatosis, only 12% develop in the

head and neck region.30

Substantial controversy exists about the manage-

ment of AF. The treatment options include surgery,

chemotherapy, hormonal therapy, and radiotherapy,

either individually or combined. The reference stan-

dard treatment with the least chance of recurrence isprimary surgical excision with a clear margin.8 How-

ever, that will not always be possible, because of the

invasive nature of the tumor with poorly defined mar-

gins. Because most AFs of the head and neck tend to

involve the internal carotid artery, base of skull,

FIGURE4. A,B, Photomicrographs showing proliferation of spindle cells with bland nuclei and abundant collagen fibers arranged in a uniformdirection (hematoxylin-eosin stain, original magnification �100).



supraclavicular fossa, brachial plexus, and other vital

structures,31 it becomes more challenging to perform

en bloc resection. Obtaining negative margins is even

more difficult in the pediatric age group because of the

more invasive nature of lesion in this age group. Whenthe tumor can be resected with negative margins with-

out functional and cosmetic impairment, it should be

resected with negative surgical margins and moni-

tored in all age group patients. In cases in which neg-

ative margins cannot be obtained, gross resection of

the tumor followed by adjuvant therapy is indicated.

When treating growing patients with AF involving

the bone, the surgeon should balance the need to ob-

tain negative margins and the need for the face to be

able to grow. This is because in skeletally immature pa-tients, if the continuity of bone is maintained, it is ca-

pable of remodeling to its initial shape by

subperiosteal ossification, just as occurred in our pa-

tient 3. In our study, the recurrence rate was low

when either negative margins were obtained or

FIGURE 5. Treatment algorithm of aggressive fibromatosis summarized in a flow chart.


WANG ET AL 319

adjunct therapy was given. The correlation betweennegative surgical margins and a lower rate of recur-

rence has been supported by various studies, includ-

ing Faulkner et al8 (75% vs 15%), Buitendijk et al1

(67% vs 16%), Bertani et al32 (46.4% vs 7.1%), and

Shido et al33 (57.89% vs 42.1% for positive surgical

margins vs negative surgical margins, respectively).

In contrast, Gronchi et al13 have reported that the

risk of recurrence was independent of margin statusand that the presence of positivemargins did not affect

long-term disease-free survival. This has been further

supported by Hoos et al34 and Merchant et al,35 who

reported that rate of local recurrence is independent

of the surgical margin status and the presence of resid-

ual disease does not adversely affect the 5-year disease-

free survival or overall survival rate; thus, attempts to

achieve negative resection margins could result in un-necessary morbidity, with sacrifice of major functional

and cosmetic elements.

Controversy continues with the role of radiotherapy

in different age groups. For adult patients with gross or

microscopic residual tumor, we recommend fraction-

ated radiotherapy using beam energies of colbalt-60,6- to 20-MV photons, and electrons, depending on the

region and site of tumor involvement, once daily, 5

days/week with a fraction size of 1.8 Gy and total

dose of 55 Gy or more. Goy et al,36 Micke et al,37 and

Kamath et al38 also reported that radiotherapy can pro-

vide a high local control rate in the postoperative set-

ting and for unresectable or partially resectable

tumors. Guadagnolo et al,39 in a case series of 115 pa-tients treated with radiotherapy alone or combined

with surgery, showed local control rates at 5 years

and 10 years of 75% and 74%, respectively. They also

concluded that doses greater than 56 Gy are not neces-

sary for gross disease control. However, this was chal-

lenged by Rutenberg et al,23 who reported a local

control rate for tumors receiving doses greater than

55 Gy and less than 55 Gy of 79% and 30%, respectively.Long-term cosmetic impairment, functional mor-

bidity, growth disturbance, contracture, the risk of

developing second malignancies, and poor recur-

rence control22 are of concern, making radiotherapy

an unsuitable treatment measure for skeletally


immature patients. Merchant et al,18 in a case series

of 13 pediatric patients undergoing radiotherapy for

desmoids tumor, showed that 10 of 13 patients had

developed local recurrence, 3 patients had died of

disease, 8 patients had severe radiation-associated

complication, and only 1 patient remained with

locally controlled disease. The recently published

study by Rutenberg et al23 also showed that thelocoregional control rate for patients younger than

18 years old who had undergone external beam

radiotherapy was only 20%; however, in those aged

18 to 30 years, it was 63%. In the same study, 40%

of patients experienced severe complications, includ-

ing pathologic fractures, pain, contracture, impaired

range of motion, and skin cancer.23

Chemotherapy plays a major role in inducinggrowth arrest and tumor stabilization in slowly evolv-

ing pediatric AF.26 Chemotherapy regimens using

either VBL and MTX or ifosfamide and etoposide,

with or without mitomycin, doxorubicin, and cisplatin

have met with some success. Nonrandomized, retro-

spective reports have described both objective disease

regression and symptomatic relief, with a few patients

experiencing long-term remission that persistedeven after treatment cessation.28,40 A phase II study

conducted within the Pediatric Oncology Group by

Skapek et al27 reported that VBL and MTX are well tol-

erated in children and that the administration of MTX

at a dose of 50 mg/m2 and VBL at a dose of 10 mg/m2

weekly or MTX combined can block tumor growth or

promote tumor regression in most children. Weiss and

Lackman28 also reported symptomatic relief in allpatients treated with weekly VBL, to a maximum

dose of 10 mg/week, and MTX, to a maximum dose

50 mg/week.

We prefer the combination of MTX and VBL to

other cytotoxic drugs, because it has a better risk/

benefit ratio and results in a lower local recurrence

rate in children. Although the study by Van der Hul

et al41 reported that MTX and VBL results in an unac-ceptable toxicity level and cannot be recommended

for children, our experience did not match theirs.

This might have been because of the lower dose of

VBL (10 mg/m2 compared with 5 mg/m2) and the

shorter therapy duration (1 year vs 6 months of

a weekly dose in our study). The side effects of MTX

plus VBL include nausea, polyneuropathy, fatigue, leu-

kopenia, impaired liver function, dyspnea, and MTX-induced pneumonitis. All our patients tolerated the

low-dose chemotherapy well, with mild nausea and

vomiting as the most common side effects.

Other chemotherapeutic agents such as tamoxi-

fen42 and imatinib21 have been tested in a phase II trial

and were found effective in controlling progression

and locoregional control; however, the trial did not in-

clude children. Thus, we should wait a few years until

such studies have been conducted with children. Our

treatment algorithm is summarized in Figure 5.

In conclusion, the age of the patient plays an impor-

tant role in the selection of a treatment plan for AF in

the head and neck region. Pediatric AF, although

aggressive, is still a benign lesion and lacks metastatic

potential. Conservative surgery with preservation of

the form and function should be targeted, ratherthan aggressive mutilating surgery to achieve negative

surgical margins in exchange for impaired growth,

esthetics, and function. Microscopic and macroscopic

residual tumor should be treated with adjuvant low-

dose chemotherapy in children and radiotherapy in

adults. A better understanding of the molecular and

genetic basis for AF could result in targeted therapy

with minimal toxicity profiles and could become thepreferred therapy in the near future.

References

1. Buitendijk S, van de Ven CP, Dumans TG, et al: Pediatric aggres-sive fibromatosis: A retrospective analysis of 13 patients andreview of literature. Cancer 104:1090, 2005

2. Janinis J, Patriki M, Vini L, et al: The pharmacological treatmentof aggressive fibromatosis: A systematic review. Ann Oncol 14:181, 2003

3. Seper L, Burger H, Vormoor J, et al: Aggressive fibromatosis in-volving the mandible—Case report and review of the literature.Oral Surg Oral Med Oral Pathol Oral Radiol Endod 99:30, 2005

4. Zhou Y, Zhang Z, Fu H, et al: Clinical management of pediatricaggressive fibromatosis involving the mandible. Pediatr BloodCancer 59:648, 2012

5. Reitamo JJ, Scheinin TM, Hayry P: The desmoid syndrome: Newaspects in the cause, pathogenesis and treatment of the desmoidtumor. Am J Surg 151:230, 1986

6. Wilkins SA Jr, Waldron CA, Mathews WH, Droulias CA: Aggres-sive fibromatosis of the head and neck. Am J Surg 130:412,1975

7. Tejpar S, Nollet F, Li C, et al: Predominance of beta-cateninmutations and beta-catenin dysregulation in sporadic aggres-sive fibromatosis (desmoid tumor). Oncogene 18:6615,1999

8. Faulkner LB, Hajdu SI, Kher U, et al: Pediatric desmoid tumor:retrospective analysis of 63 cases. J Clin Oncol 13:2813, 1995

9. Wanjeri JK, Opeya CJ: A massive abdominal wall desmoid tumoroccurring in a laparotomy scar: A case report. World J SurgOncol 9:35, 2011

10. Bertario L, Russo A, Sala P, et al, for the Hereditary ColorectalTumor Registry: Multiple approach to the exploration ofgenotype-phenotype correlations in familial adenomatous poly-posis. J Clin Oncol 21:1698, 2003

11. Carothers AM, Rizvi H, Hasson RM, et al: Mesenchymal stromalcell mutations and wound healing contribute to the etiology ofdesmoid tumors. Cancer Res 72:346, 2012

12. Wu C, Amini-Nik S, Nadesan P, et al: Aggressive fibromatosis(desmoid tumor) is derived frommesenchymal progenitor cells.Cancer Res 70:7690, 2010

13. Gronchi A, Casali PG, Mariani L, et al: Quality of surgery and out-come in extra-abdominal aggressive fibromatosis: A series ofpatients surgically treated at a single institution. J Clin Oncol21:1390, 2003

14. Dormans JP, SpiegelD,Meyer J, et al: Fibromatoses inchildhood:Thedesmoid/fibromatosis complex. Med Pediatr Oncol 37:126, 2001

15. Sorensen A, Keller J, Nielsen OS, Jensen OM: Treatment ofaggressive fibromatosis: a retrospective study of 72 patients fol-lowed for 1-27 years. Acta Orthop Scand 73:213, 2002

http://refhub.elsevier.com/S0278-2391(13)00928-2/sref1












































WANG ET AL 321

16. Ballo MT, Zagars GK, Pollack A, et al: Desmoid tumor: Prognosticfactors and outcome after surgery, radiation therapy, or com-bined surgery and radiation therapy. J Clin Oncol 17:158, 1999

17. Ballo MT, Zagars GK, Pollack A: Radiation therapy in themanage-ment of desmoid tumors. Int J Radiat Oncol Biol Phys 42:1007,1998

18. Merchant TE, Nguyen D,Walter AW, et al: Long-term results withradiation therapy for pediatric desmoid tumors. Int J RadiatOncol Biol Phys 47:1267, 2000

19. Plukker JT, van Oort I, Vermey A, et al: Aggressive fibromatosis(non-familial desmoid tumour): Therapeutic problems and therole of adjuvant radiotherapy. Br J Surg 82:510, 1995

20. Chugh R, Wathen JK, Patel SR, et al, for the Sarcoma Alliance forResearch through Collaboration: Efficacy of imatinib in aggressivefibromatosis:Results of aphase IImulticenter SarcomaAlliance forResearch through Collaboration (SARC) trial. Clin Cancer Res 16:4884, 2010

21. Penel N, Le Cesne A, Bui BN, et al: Imatinib for progressive and re-current aggressive fibromatosis (desmoid tumors): An FNCLCC/French Sarcoma Group phase II trial with a long-term follow-up.Ann Oncol 22:452, 2011

22. Spiegel DA, Dormans JP, Meyer JS, et al: Aggressive fibromatosisfrom infancy to adolescence. J Pediatr Orthop 19:776, 1999

23. Rutenberg MS, Indelicato DJ, Knapik JA, et al: External-beamradiotherapy for pediatric and young adult desmoid tumors.Pediatr Blood Cancer 57:435, 2011

24. Reich S, Overberg-Schmidt US, Buhrer C, Henze G: Low-dosechemotherapy with vinblastine and methotrexate in childhooddesmoid tumors. J Clin Oncol 17:1086, 1999

25. Skapek SX, Hawk BJ, Hoffer FA, et al: Combination chemother-apy using vinblastine andmethotrexate for the treatment of pro-gressive desmoid tumor in children. J Clin Oncol 16:3021, 1998

26. Azzarelli A, Gronchi A, Bertulli R, et al: Low-dose chemotherapywith methotrexate and vinblastine for patients with advancedaggressive fibromatosis. Cancer 92:1259, 2001

27. Skapek SX, Ferguson WS, Granowetter L, et al, for the PediatricOncology Group: Vinblastine and methotrexate for desmoid fi-bromatosis in children: results of a Pediatric Oncology Groupphase II trial. J Clin Oncol 25:501, 2007

28. Weiss AJ, Lackman RD: Low-dose chemotherapy of desmoidtumors. Cancer 64:1192, 1989

29. Goldblum JR, Fletcher JA: Desmoid-type fibromatoses. In:Fletcher CDM, Unni KK, Mertens F, (eds). Pathology and Genet-

ics of Tumours of Soft Tissue and Bone: World Health Organiza-tion Classification of Tumours. Lyon, France: InternationalAgency for Research on Cancer (IARC) Press, 2002, pp 83–84

30. Kruse AL, Luebbers HT, Gratz KW, Obwegeser JA: Aggressivefibromatosis of the head and neck: A new classification basedon a literature review over 40 years (1968-2008). Oral MaxillofacSurg 14:227, 2010

31. Wang CP, Chang YL, Ko JY, et al: Desmoid tumor of the head andneck. Head Neck 28:1008, 2006

32. Bertani E, Testori A, Chiappa A, et al: Recurrence and prog-nostic factors in patients with aggressive fibromatosis. Therole of radical surgery and its limitations. World J Surg Oncol10:184, 2012

33. Shido Y, Nishida Y, Nakashima H, et al: Surgical treatment for lo-cal control of extremity and trunk desmoid tumors. ArchOrthopTrauma Surg 129:929, 2009

34. Hoos A, Lewis JJ, Urist MJ, et al: Desmoid tumors of the head andneck—A clinical study of a rare entity. Head Neck 22:814, 2000

35. Merchant NB, Lewis JJ, Woodruff JM, et al: Extremity and trunkdesmoid tumors: A multifactorial analysis of outcome. Cancer86:2045, 1999

36. Goy BW, Lee SP, Fu YS, et al: Treatment results of unresected orpartially resected desmoid tumors. Am J Clin Oncol 21:584,1998

37. Micke O, Seegenschmiedt MH, German Cooperative Group onRadiotherapy for Benign Disease: Radiation therapy foraggressive fibromatosis (desmoid tumors): Results of a national-Patterns of Care study. Int J Radiat Oncol Biol Phys 61:882, 2005

38. Kamath SS, Parsons JT, Marcus RB, et al: Radiotherapy for localcontrol of aggressive fibromatosis. Int J Radiat Oncol Biol Phys36:325, 1996

39. Guadagnolo BA, Zagars GK, Ballo MT: Long-term outcomes fordesmoid tumors treated with radiation therapy. Int J RadiatOncol Biol Phys 71:441, 2008

40. Okuno SH, Edmonson JH: Combination chemotherapy for des-moid tumors. Cancer 97:1134, 2003

41. van der Hul RL, Seynaeve C, van Geel BN, Verweij J: Low dosemethotrexate and vinblastine, givenweekly to patientswith des-moid tumours, is associated with major toxicity. Sarcoma 7:153,2003

42. Morris LG, Sikora AG, Kuriakose MA, DeLacure MD: Tamoxifentherapy for aggressive fibromatosis of the posterior triangle ofthe neck. Otolaryngol Head Neck Surg 136:674, 2007




















































































Documents

Age-Based Treatment of Aggressive Fibromatosis in the Head and Neck Region