Documente Academic
Documente Profesional
Documente Cultură
DOI 10.1007/s00405-016-3899-3
Abstract The purpose of this study is to report our Keywords Head and neck Outcomes Radiation
institutional experience using radiotherapy in the treatment therapy
of ameloblastoma and ameloblastic carcinoma. Three
patients with ameloblastoma and 3 patients with
ameloblastic carcinoma were treated with radiotherapy Introduction
alone (2 patients) or surgery and postoperative radiother-
apy (4 patients) at the University of Florida between 1973 Ameloblastomas are rare benign tumors that comprise
and 2007. Follow-up ranged from 4.0 to 13.1 years with a approximately 19 % of all odontogenic neoplasms. Behind
median of 7.8 years. Radiotherapy complications were odontomas, they are the second most common tumor in the
scored using the Common Terminology Criteria for odontogenic family of tumors. They are slow-growing,
Adverse Events, version 4.0. Local control was achieved in locally invasive tumors that arise primarily from the molar-
4 of the 6 patients. One patient treated with RT alone for an ramus region of the mandible (80 %), with almost all
unresectable ameloblastoma developed a local recurrence remaining cases occurring in the maxilla [1]. There have
and metastases in both the cervical lymph nodes and lungs, been rare reports of tumors arising from soft tissues as well,
but had excellent response to dual BRAF/MEK inhibition representing 2 % of cases, designated peripheral
with dabrafenib and trametinib. Another patient treated ameloblastomas [2].
with surgery and postoperative radiotherapy for an These tumors typically manifest as a painless swelling
ameloblastic carcinoma recurred locally without metasta- mass of the mandible or maxilla. Less common pre-
sis, but was not salvaged. No significant treatment-related senting symptoms include paresthesias and tooth dis-
complications were observed. For patients with local placement. A history of a painful lesion exhibiting rapid
recurrence or inadequate margins after surgery, adjuvant growth is more suggestive of ameloblastic carcinomas.
radiotherapy provides the potential for disease control. In As these tumors arise from the bone itself, ameloblas-
the setting of metastatic disease, targeted therapies may tomas may present incidentally via routine dental
provide an additional opportunity for salvage. X-rays, up to one-third of the time in one series [3].
These tumors typically arise in middle adulthood, with a
median age of 35 years with no apparent sex predilec-
& William M. Mendenhall tion, although these tumors most likely begin growing
mendwm@shands.ufl.edu many years prior as there have been reports of diagnosis
1
Department of Radiation Oncology, University of Florida
in children as young as 12 years [4]. The risk of
College of Medicine, 2000 SW Archer Rd., developing these tumors is fivefold greater among
PO Box 100385, Gainesville, FL 32610-0385, USA African Americans than among whites [5].
2
Department of Otolaryngology, University of Florida College While several theories have been presented suggesting
of Medicine, Gainesville, FL, USA the origin of these tumors, ameloblastomas likely arise
3
Department of Medicine, University of Florida College of from enamel epithelium and the ectomesenchymal cells
Medicine, Gainesville, FL, USA that play an important role in odontogenesis. They are
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Results Discussion
Local control after RT was observed in four of six patients Surgery is well established as the primary initial treatment
(67 %). Of these four, two are alive with no evidence of modality, preferably with wide local excision taking ade-
disease and two died of intercurrent disease. Two patients quate margins. Literature reporting experiences with less-
developed both a local recurrence as well as metastases. Of extensive operations, such as enucleation, electrocautery,
these, the first patient recurred locally and simultaneously and marsupialization, have resulted in very high rates of
developed neck and superior chest dermal metastases at local recurrence, ranging from 65 % to over 90 % in a
3.7 years after surgery and postoperative RT for an series of 92 patients with ameloblastoma treated with
ameloblastic carcinoma, at which point the patient opted for curettage alone [16]. More extensive wide local excisions
best supportive care. The patient passed away several months with up to 1- to 2-cm margins for ameloblastoma and up to
later with evidence of disease. The second patient was treated 3 cm for ameloblastic carcinoma with bone reconstruction
with RT alone for a locally recurrent incompletely provide much more acceptable rates of local control and
resectable ameloblastoma after multiple surgical procedures are considered the cornerstone of primary ameloblastoma
at outside institutions. He subsequently developed tumor management. Olaitain et al. have published the largest
recurrence in the region of his mandibular reconstruction as surgical ameloblastoma series to date. They reported 229
well as the bilateral neck including the left level V, and right cases treated with wide local excision with a recurrence
level IB at 5.7 years after RT. At 6.3 years after RT, CT rate of 10 % at 2–18 years after surgery (median follow-up
imaging revealed an obstructing right middle lobe endo- was not reported) [17]. All six of our patients underwent at
bronchial lesion as well as multiple subcentimeter intrapul- least one surgical excision either at our institution or an
monary and left hilar nodules, confirmed as metastatic outside institution before RT.
disease via biopsy. He was then treated with dabrafenib and As these tumors are rare and surgery is the primary
trametinib, resulting in a complete resolution of all pul- modality of treatment, data reporting outcomes after RT
monary metastatic disease and a partial response in the jaw remain scarce. The initial Memorial Sloan-Kettering Can-
and neck disease as confirmed by positron emission cer Center (New York, NY) experience reporting patients
tomography–computed tomography scan 8 weeks after treated with RT between 1921 and 1951 is one of the
treatment [15]. This patient is currently alive with sustained earliest and largest series published [16]. They reported
complete response of pulmonary metastases and continued eventual recurrences in all 11 patients treated, although
partial response in the jaw and neck. dose and fractionation details were not described [16]. In
No patient suffered a severe treatment-related another older series published in 1937, Robinson found a
complication. recurrence rate of 72 % in 18 patients treated with RT [18].
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Unsurprisingly, ameloblastomas and ameloblastic carci- recurrent disease when combined with surgery. While
nomas were long considered radioresistant tumors, as older platinum-based chemotherapeutic regimens have resulted
methods failed to provide appreciable benefit to patients. in either no response or partial response, agents such as
However, more recent reports suggest RT may benefit dabrafenib/trametinib and arsenic trioxide targeting
postoperative patients who have locally recurred or those molecular aberrations in the SHH and MAPK pathways,
with residual disease after resection. This may be in part respectively, may serve as important modalities in either
owing to improvements in treatment techniques, as older locally recurrent or distant disease.
series often used orthovoltage irradiation and radium needles
Compliance with ethical standards
instead of megavoltage irradiation. Princess Margaret Can-
cer Center (Toronto, Ontario) reported their series of 10 Conflict of interest None.
patients treated with RT from 1958 to 1982, with a recur-
rence rate of 20 % [19]. Miyamoto et al. reported local
control in a patient treated with RT and provided treatment
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