Medication-Related Osteonecrosis of the Jaw Guideline

An interview with Dr. Noam Yarom, Dr. Charles Shapiro, Dr. Deborah Saunders and Dr. Doug Peterson on "Medication-Related Osteonecrosis of the Jaw: MASCC/ISOO/ASCO Clinical Practice Guideline." This guideline addresses the prevention and management of MRONJ in patients with cancer. This guideline is intended for oncologists and other physicians, dentists, dental specialists, oncology nurses, clinical researchers, oncology pharmacists, advanced practitioners, and patients with cancer. Read the full guideline at www.asco.org/supportive-care-guidelines

Find all of the ASCO podcasts at podcast.asco.org

TRANSCRIPT

Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

Hello, and welcome to the ASCO Guidelines podcast series. My name is Shannon McKernin. And today, I'm interviewing a panel of authors from "Medication-Related Osteonecrosis of the Jaw: MASCC/ISOO/ASCO Clinical Practice Guideline." So could I have you each introduce yourselves for the listeners today?

Thank you, Shannon. I'm Dr. Deborah Saunders. I'm the president of the International Society of Oral Oncology and was the section head for the Systematic Review on "Medication-Related Osteonecrosis of the Jaw," with MASCC and ISOO. I was a proud part of the steering committee and one of the authors.

Thank you, Debbie. My name is Dr. Douglas Peterson. I am professor of oral medicine in the School of Dental Medicine at the University of Connecticut Health Center in Farmington, Connecticut. I am also a faculty member in the Head and Neck Cancer Oral Oncology Program at the university's Neag Comprehensive Cancer Center. I'm a member of the steering committee for this clinical practice guideline and one of the co-authors as well. In addition, and as of June 2019, I have been serving as chair elect during this next year for ASCO's Clinical Practice Guidelines committee.

Thank you, Doug. My name is Noam Yarom. I'm an all medicine specialist from the Sheba Medical Center in Tel Aviv University in Israel. I'm serving as a culture of this guideline, and it is a pleasure to be with you today.

Thanks, Noam. I am Dr. Charles Shapiro, professor of medicine at the Mt. Sinai Hospital in New York. And I'm co-chair of the guideline "Medical-Related Osteonecrosis of the Jaw." And I'm happy to be here.

Thank you all for being here today to discuss this guideline on the podcast. So first, can you give us a general overview of what this guideline covers.

Sure. So you know, ASCO and MASCC, as well as ISOO decided that it would be great to provide a practical evidence-based approach in a multidisciplinary type setting to address this important topic that impacts all of our professions, that being medication-related osteonecrosis of the jaw. It's terminology and its definition and the path that's varied and even part of this publication identifies the need for us to move forward with a concise definition and similar terminology, that being medication-related osteonecrosis of the jaw. Medication-related osteonecrosis of the jaw is defined as the presence of an exposed or bone that is probable by a probe in a patient that has a history or is undergoing present use of a bone-modifying agent. This being in the absence of any patients having received any radiation to the head and neck and the absence of metastatic lesions to the jaw. The importance of us identifying this definition and agreeing on the terminology allows us to move forward in future publication to better compare outcome and provide better prevention and treatment for our patients moving forward.

And what are the key recommendations of this guideline?

There are six clinical questions associated with this clinical practice guideline as well as a series of recommendations built within each of the clinical questions. Clinical question one is directed to the preferred terminology and definition for osteonecrosis of the jaw, both of the maxilla and the mandible, as associated with pharmacologic therapies in oncology patients. The panel recommends that the term medication-related osteonecrosis of the jaw, MROJ, be used when referring to bone necrosis associated with pharmacologic therapies. As Dr. Saunders has described, the definition contains three key elements-- current or previous treatment with a bone-modifying agent or angiogenic inhibitor, exposed bone, or bone that can be probed through an intra or extra-oral fistula in the maxillofacial region and that has persisted for longer than eight weeks. And third, no history of radiation therapy to the jaws and no history of metastatic disease to the jaws. Clinical question two is directed to specific steps that should be taken to reduce the risk of MRONJ. The recommendation begins with emphasizing the absolute importance of interprofessional communication of the oncology team with the dental team in advance of initiating the bone-modifying agent. For patients with cancer who are scheduled to receive a bone-modifying agent in a non-urgent setting, a comprehensive oral care assessment, including dental examination and periodontal examination and an oral radiographic exam when feasible to do so should be undertaken prior to initiating the BMA therapy. Once the dental care plan has been developed, it should be discussed with the dental team, the patient, and the rest of the oncology team and then implemented based on medically necessary dental procedures. These procedures should be performed prior to the initiation of the bone-modifying agent. Once the bone-modifying agent is implemented, there should be ongoing followup by the dentist on a routine schedule, for example, every six months following initiation of the BMA therapy. It's also important to realize that there are a series of modifiable risk factors which should be emphasized with the patient. For example, poor oral health, invasive dental procedures, ill-fitting dentures, uncontrolled diabetes mellitus, and tobacco use are all factors that have been associated with development of a MRONJ. All of these modifiable risk factors should be addressed, where appropriate, with the patient in advance of the bone-modifying agent. As far as elective dental alveolar surgery, these procedures, if they are not medically necessary, for example, extractions or alveoloplasties or implants, they should not be performed during active therapy with a bone-modifying agent being given at an oncologic dose. Now, exceptions to this may be considered when a dental specialist with expertise in prevention and treatment of MROJ has reviewed the benefits and risks of the proposed invasive procedures with the patient and the oncology team. In general, however, elective dental alveolar surgical procedures should be deferred while the patient is undergoing active therapy with a bone-modifying agent. If the dental alveolar surgery is performed, the patient should be evaluated by a dental specialist on a systematic and frequently scheduled basis, for example, every six to eight weeks until there is full mucosal coverage of the surgical site. And once again, communication between the dental team and the rest of the oncology team is absolutely paramount in assuring ongoing comprehensive care of the patient. Interestingly, there are still questions in the literature relative to whether or not there should be temporary discontinuation of bone-modifying agents prior to dental alveolar surgery. Unfortunately, there remains insufficient evidence to support or refute the need for discontinuation of the bone-modifying agent prior to dental alveolar surgery. And so the administration of the bone-modifying agent may be deferred at the discretion of the treating physician, in conjunction with discussion with the patient and the oral health provider. So it really becomes an individual judgment call by the treating physician relative to whether or not to temporarily discontinue the bone-modifying agent prior to dental alveolar surgery. Clinical question three involves the staging of MROJ. There are a number of well-established staging systems in the literature addressing severity and extent of MROJ. For example, the 2014 American Academy of Oral and Maxillofacial Surgeons Staging System is one example. Another example is the National Cancer Institute's Common Terminology Criteria For Adverse Events. And there is a 2017 International Task Force on O and J Staging System for MROJ that is available as well. So there are at least three well-established, widely utilized staging systems for MROJ. Having said this, it's important in the view of the panel that the same staging system should be used throughout an individual patient's MROJ course of care. And optimally, the staging should be performed by a clinician experienced with the management of MROJ. Clinical question four involves management of MROJ directly. Here, the recommendations talk in terms of initial treatment of MROJ, which is centered in conservative measures. Now, these conservative measures may include antimicrobial mouth rinses, antibiotics if clinically indicated, effective oral hygiene, and conservative surgical intervention such as a removal of a superficial bone spicule. In cases, however, of refractory MROJ, more advanced MROJ, aggressive surgical interventions, for example, mucosal flap elevations, bloc resections of necrotic bone may be used if MROJ is persisting and severely affects function despite conservative initial treatment. Clinical question five involves bone-modifying agents and whether they should be temporarily discontinued after a diagnosis of MROJ has been established. And once again, there is insufficient evidence to support or refute the discontinuation of the bone-modifying agents after a diagnosis of MROJ has been established. The bone-modifying agent may be deferred at the discretion of the treating physician, again in discussion with the patient and the oral health care provider. And finally, clinical question six involves what outcome measures that should be utilized in clinical practice to describe the response of MROJ lesion to treatment. During the course of MROJ treatment, the dentist, dental specialist, should communicate with a medical oncologist in an ongoing way, both the objective and subjective status of the lesion. The guideline presents a scale that can be utilized to describe the trajectory of the MROJ-- resolved, improving, stable, or progressive. The clinical course of MROJ may impact both local and systemic treatment decisions relative to the cessation or the recommencement of bone-modifying agents. So once again, it becomes very, very important that the ongoing interprofessional communication relative to the clinical course of MROJ-- resolved, improving, stable, or progressive-- be discussed with the oncology team.

Great. Thank you, Dr. Peterson. So on that last note, how can oncologists, dental specialists, and dentists all work together to manage medication-related osteonecrosis of the jaw?

Throughout these guidelines, we do emphasize the importance of collaboration among the cancer care team, dentist, and dental specialists in order to coordinate care and modify risk factors. It is very important that cancer care team and the dental care team speak the same language. Therefore, we spend time on clarifying the definitions, the diagnostic criteria, and staging of MROJ. As been said earlier, we have developed a new system to evaluate the response to treatment, which is based both on objective findings and symptoms. By using this scale, oncologists and dentists would be able to communicate more easily for the benefit of the patients. We emphasized the need for multidisciplinary discussion in a few critical points throughout the course of bone-modifying agent therapy. And it is most important in case of a planned oral surgery in a patient without MROJ or before aggressive surgical treatment of refractory MROJ.

And how will these guideline recommendations affect patients, and what should they talk to their doctors about?

There are a number of things that patients, providers, dental specialists, and medical oncologists can do to lessen the risk and prevent MROJ. Because the key to MROJ is prevention. Once MROJ is established, it's difficult to treat, impacting a patient's quality of life. So we want to prevent, reduce the risk of developing MROJ. Patients can do a number of things-- pursue good oral hygiene, stop smoking, or reduce smoking, and control their diabetes, for example. Those things lessen the risk of MROJ. Providers, dental providers, dental specialists, who are specialized in the area or providers, dentists otherwise in the community, when they encounter a patient that's contemplating bone-modifying agents, they can do what's called a complete dental screening exam, which involves a complete examination of the mouth, Panorex X-rays and X-rays as clinically indicated. We want to identify work in the mouth that needs to be repaired before initiating bone-modifying agents. That way, we don't have to deal with an emergent situation when it could be preventable prior to bone-modifying agents, because one of the single highest risk factors for MROJ is emergent dental work while you're on bisphosphonate or another anti-resorptive agent-- bone-modifying agents. So a dental screening exam is critical to prevent or reduce the risk of MROJ. And medical oncologists have a role too in communication with the dental specialists and really think hard about the indications for bone-modifying agents, whether it be for osteoporosis, whether it be for metastatic disease, and whether it be for anti-cancer effects.

And finally, where can both patients and clinicians go to get more information on this topic or to find a dentist or a dental specialist?

Now, as far as websites, ASCO, MASCC, and ISSO all have websites you can go to to find out more information about MROJ.

Yeah, I think that's great advice. Our links for additional information are listed in the Clinical Practice Guideline as well. This is a really first step at a framework in trying to manage a side effect that affects our patients but is very multidisciplinary. And like Dr. Shapiro was saying, really the best way to prevent this is with proper communication between the dentist and the oncologist and making the patient aware of what is needed prior to commencement of these treatments.

Well, it certainly sounds as though there are some important considerations for clinicians and patients. And I really hope that this guideline is widely read and makes a real impact on the management of osteonecrosis and the communication between oncologists, dental specialists, and dentists. So from me and all of our listeners, thank you all for coming on the podcast today to discuss "Medication-Related Osteonecrosis of the Jaw: MASCC/ISOO/ASCO Clinical Practice Guideline."

Thank you. Thank you for having us. Thank you very much for this opportunity to contribute to this important discussion. Thank you for allowing me to participate in this important podcast.

And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast series. To read the full guideline, go www.asco.org/supportive-care-guidelines. And if you've enjoyed what you've heard today, please rate and review the podcast and refer the show to a colleague.