Page 35 - GP Fall Final 2017

chemotherapy solution) may be employed mune response against malignant cells on cancer and metastatic bone disease. The risk
for melanomas on the arm or leg. Target- the skin. of MRONJ is influenced by the potency of
ed therapy, immunotherapy, chemotherapy, the bisphosphonate and its duration of use.
or biochemotherapy (immunotherapy and Targeted Therapy It is higher in parenteral administration than
chemotherapy) may also be utilized. The Melanoma cells may have components that oral and with longer duration of treatment,
treatment for Stage IV is more challenging can serve as targets for targeted therapy especially if it exceeds four years. There is
as melanomas have metastasized to distant and offer a treatment with less severe side a higher incidence of MRONJ when the an-
lymph nodes or other areas. Surgery or ra- effects. At least 50% of melanomas display tiresorptive therapy is indicated for cancer
diation therapy can be employed for skin mutations in the BRAF gene. The altered rather than osteoporosis or Paget’s disease.
tumors or enlarged symptomatic nodes. BRAF permits the melanoma cells to grow. There appears to be a higher incidence of
Metastases that are symptomatic and cannot If a tested biopsy sample reveals a BRAF MRONJ observed among patients who are
be resected will require treatment with radi- mutation, targeted therapies against BRAF taking an antiresorptive medication along
ation, immunotherapy, targeted therapy, or or MEK can be implemented. Dabrafenib with an antiangiogenic medication. Inva-
chemotherapy. (Tafinlar) and Vemurafenib (Zelberaf) are sive dental procedures, specifically dentoal-
BRAF inhibitors that reduce the size or im- veolar surgery, or concomitant oral disease
In cases of recurrent melanoma, treatment pede the growth of tumors. Trametinib (Me- increase the risk of MRONJ. However,
will depend on the stage of the initial mela- kinist) and cobimetinib (Cotellic) are MEK MRONJ may occur spontaneously in the
noma, previous treatments, and the location inhibitors. The MEK gene works in coordi- absence of any precipitating event.
of the new melanoma, along with other fac- nation with the BRAF gene; therefore, they
tors. Melanoma can recur in distant areas can be used in the treatment of melanomas Prior to beginning treatment with an antire-
of the body, affecting any organ but most with BRAF gene mutations. The combina- sorptive agent and perhaps an antiangiogen-
often the site will be the lungs, bones, liver, tion of BRAF and MEK inhibitors appear to ic agent, patients should be advised of the
or brain. reduce tumor size for longer time intervals potential occurrence of MRONJ and be en-
than the use of either inhibitor administered couraged to undergo a comprehensive den-
Melanoma: Treatment Options on its own. Imatinib (Gleevec) and nilotinib tal examination, eliminate non-restorable
The treatment options 19,11 available for mel- (Tasigna) are administered to target muta- and questionable teeth, optimize periodon-
anoma are surgery, immunotherapy, target tions in the C-KIT gene which are observed tal health, and implement preventive dental
therapy, chemotherapy, and radiation thera- in a minority of melanoma cases. care. If antiresorptive therapy has not been
py. As previously mentioned, treatment will initiated, consider a delay to allow the site
be determined by the stage of melanoma Chemotherapy to mucosalize (10-14 days) or to permit ade-
and other factors. For early stage melano- Chemotherapy may be used in the treatment quate osseous healing. Oral hygiene should
ma, surgery is the main treatment option. In of advanced melanomas and include dacar- be monitored closely. Minor dental proce-
cases where lymph node dissection is indi- bazine (DTIC), temozolomide, nab-pacli- dures which preserve the root, such as a cor-
cated, one of the long term side effects is taxel, paclitaxel, cisplatin, carboplatin, and onectomy, are preferred over extractions.
lymphedema. The lymph nodes (inguinal vinblastine. It is estimated that the risk of developing
and axillary) normally drain fluid from the MRONJ subsequent to dentoalveolar surgi-
limbs. There is an increased risk of infection Radiation Therapy cal procedures is 1.5 to 3.0%. Patients with
in the limb along with the swelling. Elastic Generally, radiation therapy is not used in partial or complete oral appliances should
stockings or compression sleeves may be the treatment of melanoma on the skin, but be carefully examined for areas of trauma
used to treat the lymphedema. it may be used if surgical resection is not to the mucosa. The primary objectives of
practical. It may be used following surgery treatment for patients who are at risk or are
Immunotherapy in an area where lymph nodes have been re- confronted with MRONJ are to support the
Immunotherapy is used to stimulate the moved, especially where there was signifi- ongoing treatment for the malignancy and
immune system to recognize and to attack cant nodal involvement. It can also be used to maintain the patient’s quality of life, to
cancer cells with greater effectiveness. to treat recurrent melanoma on the skin or control pain and infection, and to prevent
Pembrolizumab (Keytruda) and nivolumab in the lymph nodes following surgical re- extension and/or establishment of new areas
(Opdivo), which target and block PD-1 on section or it can treat metastasis. Radiation of MRONJ.
T cells, help enhance the immune response therapy can provide palliative treatment to
against melanoma cells. They are admin- relieve symptoms as a result of metastasis A diagnosis of MRONJ is considered if the
istered intravenously every two to three to the brain or bones. Stereotactic radiosur- patient is currently undergoing or has under-
weeks. Ipilimunab (Yervoy) targets and gery (SRS) is a form of radiation therapy gone antiresorptive or antiangiogenic ther-
blocks CTLA-4 on T cells to enhance the that can be utilized for tumors that have me- apy, has exposed bone or bone that can be
immune response. It is administered intra- tastasized to the brain. Two versions of SRS probed through a fistula in the maxillofacial
venously every 3 weeks for 4 treatments. are Gamma Knife and linear accelerator. area which has been present for longer than
®
Interferon alpha and Interleukin-2 are cyto- In Gamma Knife treatment approximately two months, and where there has not been
®
kines that can enhance the immune response 200 beams of radiation are focused on the any radiation therapy or indication of me-
and are administered intravenously. tumor from different angles over a period of tastasis to the jawbone.
time as indicated.
Talimogene Iaherparepvec (Imlygic), which It appears that MRONJ is the result of many
is also referred to as T-VEC, is an oncolytic Medication Related Osteonecrosis of the factors among which are impaired bone re-
virus which is used in the treatment of mel- Jaw (MRONJ) pair and suppressed activity of osteoclasts,
anomas in the skin or lymph nodes that are Osteonecrosis of the Jaw (ONJ) was first impairment of vascular repair and angio-
not amenable to surgery. It is injected di- described in 2003 and it is now known as genesis, and local factors which include
12
rectly into the tumor every two weeks kill- Medication Related Osteonecrosis of the poor oral care, poorly fitting prostheses,
ing the cells directly as well as enhancing Jaw or MRONJ. While it is relatively un- and surgical manipulation or advanced peri-
the immune response. As Bacille-Calmette common, it is a potentially serious side ef- odontitis. The areas of exposed and necrotic
Guerin (BCG) can activate the immune sys- fect of treatment with antiresorptive agents, bone can be asymptomatic from weeks to
tem, its vaccine can be used in the treatment such as intravenous bisphosphonates and years but are the hallmark presentation of
of Stage III melanoma by direct injection denosumab, which are intended to mini- MRONJ, although inflammation of the ad-
into the tumor. Imiquinod (Zyclara) is a mize the risk of skeletal related events or jacent soft tissues may lead to symptoms.
topical cream that can stimulate a local im- SREs in patients who are being treated for Consistent jaw pain, tooth mobility, enlarge-

www.nysagd.org l Fall 2017 l GP 30