Salivary Gland Hypofunction and/or Xerostomia Induced by Non-Surgical Cancer Therapies: ISOO/MASCC/ASCO Guideline

An interview with Dr. Valeria Mercadante from University College London, Dr. Siri Beier Jensen from Aarhus University, and Dr. Douglas Peterson from UConn Health, authors on "Salivary Gland Hypofunction and/or Xerostomia Induced by Non-Surgical Cancer Therapies: ISOO/MASCC/ASCO Guideline." This guideline provides evidence-based recommendations for interventions to prevent, minimize, and manage salivary gland hypofunction and xerostomia in patients receiving nonsurgical cancer therapy. Read the full guideline at www.asco.org/supportive-care-guidelines. Suggest a topic for guideline development at www.surveymonkey.com/r/ascoguidelinesurvey.

TRANSCRIPT

[MUSIC PLAYING]

SPEAKER: 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.

[MUSIC PLAYING]

BRITTANY HARVEY: Hello, and welcome to the ASCO Guidelines Podcast Series brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all the shows, including this one, at podcasts.asco.org.

My name is Brittany Harvey, and today I'm interviewing Dr. Valeria Mercadante from University College London and University College London Hospitals Trust in London, United Kingdom, Dr. Siri Beier Jensen from Aarhus University in Aarhus, Denmark, and Dr. Douglas Peterson from the School of Dental Medicine and Neag Comprehensive Cancer Center UConn Health in Farmington, Connecticut, authors on "Salivary Gland Hypofunction and/or Xerostomia Induced by Non-Surgical Cancer Therapies: International Society of Oral Oncology, Multinational Association of Supportive Care in Cancer, and American Society of Clinical Oncology Guideline."

Thank you for being here, Dr. Mercadante, Dr. Beier Jensen, and Dr. Petersen.

DR. VALERIA MERCADANTE: Thank you. It's a pleasure to be here.

DR. DOUGLAS PETERSON: Thank you.

DR. SIRI BEIER JENSEN: Thank you.

BRITTANY HARVEY: First, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The full conflict of interest information for this guideline panel is available online with the publication of the guideline in the Journal of Clinical Oncology. Dr. Mercadante, do you have any relevant disclosures that are directly related to this guideline topic?

DR. VALERIA MERCADANTE: No, I do not have any relevant disclosure.

BRITTANY HARVEY: Thank you. And Dr. Beier Jensen, do you have any relevant disclosures that are directly related to this guideline?

DR. SIRI BEIER JENSEN: No, I have no conflicts to declare related to this guideline topic.

BRITTANY HARVEY: Thank you. And finally, Dr. Peterson, do you have any relevant disclosures that are related to this guideline topic?

DR. DOUGLAS PETERSON: No. No related conflicts to declare.

BRITTANY HARVEY: Thank you. Then let's delve into some of the content of the guideline. First, Dr. Mercadante, can you give us an overview of this guideline's scope and purpose?

DR. VALERIA MERCADANTE: Of course. These clinical practice guidelines focus on the prevention and management of salivary gland hypofunction and xerostomia due to non-surgical cancer therapies. This is something we are deeply passionate about because nonsurgical cancer therapies, including all type of radiation regimens, chemotherapy, and biological cancer therapy, can damage the glands in our mouth that produce saliva, resulting in xerostomia, which we define as patient-reported subjective sensation of dryness and salivary gland hypofunction, which we define as reduced salivary flow rate as measured objectively.

And this condition may last for several months or may become permanent. And because saliva serves so many important function, xerostomia may lead to a range of other symptoms that can impact patient quality of life. And therefore, ASCO, MASCC, and ISOO decided to update the findings of their two previous systematic reviews published in 2010 and provide a practical, evidence-based approach in a multidisciplinary setting to address this important topic.

BRITTANY HARVEY: Great. Thank you for that background. So then I'd like to review the key recommendations of this guideline. This guideline covers two clinical questions, one on prevention and one on management. So Dr. Peterson, starting with prevention, what are the key recommendations regarding pharmacologic and non-pharmacologic interventions for the prevention of salivary gland hypofunction and/or xerostomia induced by non-surgical cancer therapies?

DR. DOUGLAS PETERSON: Thank you, Brittany. As you've noted, the guideline is framed in the context of two clinical questions, prevention, and then followed by the management once the condition has occurred. Relative to prevention, there were eight recommendations, all of which were directed to reducing the risk of salivary gland hypofunction and/or xerostomia in patients with head and neck cancer. And as with other ASCO guidelines, each of these recommendations was in turn supported by text directed to literature review and analysis and clinical interpretation.

So let me just briefly highlight the eight recommendations on prevention. Recommendation 1.1 was that intensity-modulated radiation therapy, IMRT, should be used to spare major and minor salivary glands from a higher dose of radiation. This was a very strong, well-evidenced recommendation. The evidence quality was high. The strength of the recommendation was strong.

Recommendation 1.2 is that other radiation modalities that limit cumulative dose to an irradiated volume of major and minor salivary glands as one or more effectively than IMRT may be offered. Recommendation 1.3 reads that acupuncture may be offered during radiation therapy for head and neck cancer to reduce the risk of developing the symptom of xerostomia.

Recommendation 1.4, systemic administration of the sialogogue bethanechol may be offered during radiation therapy for head and neck cancer. Recommendation 1.5-- and this is an important different type of recommendation-- vitamin E or other antioxidants should not be used to reduce the risk of radiation-induced salivary gland hypofunction and xerostomia. And this is because of the potential adverse impact of these antioxidants on cancer-related outcomes and the lack of evidence of benefit.

In addition to those five recommendations, there were three recommendations for which the evidence was insufficient. In the panel's view, it was important to delineate these three recommendations in the context of current clinical practice as well as opportunities for future research that we'll talk about in a little bit.

The three recommendations for which there was insufficient evidence are 1.6. -- The panel was unable to make a recommendation for or against the use of submandibular gland transfer administered before head and neck cancer treatment. This limitation is due to the current amount of evidence associated with this surgical intervention, submandibular gland transfer, in relation to ever-evolving contemporary radiation modalities.

Recommendation 1.7-- evidence remains insufficient for a recommendation for or against use of the following three interventions during radiotherapy for head and neck cancer. The three interventions are oral pilocarpine, amifostine in association with contemporary radiation modalities, and low-level laser therapy.

And then, finally, Recommendation 1.8-- the evidence remains insufficient for or against the use of several interventions, including selected radiation technology, for example, boost radiation or hyper or hypofractionated radiation therapy, Transcutaneous Electrical Nerve Stimulation or TENS, human epidermal growth factor, and selected complementary medicines. And again, the evidence is insufficient in the panel's view for a recommendation for or against these and several other interventions that are listed in the guideline.

So I'll now turn the microphone back to Brittany.

BRITTANY HARVEY: Great. Thank you for reviewing those prevention recommendations and explaining the evidence that supported those as well. That's very helpful. So following that, Dr. Beier Jensen, what are the key recommendations on pharmacologic and non-pharmacologic interventions for the management of salivary gland hypofunction and/or xerostomia induced by non-surgical cancer therapies?

DR. SIRI BEIER JENSEN: The key recommendations for the management of salivary gland hypofunction and xerostomia induced by cancer therapies are based on the principles of stimulation of the salivary reflex and lubrication of the oral tissues of, say, the mucosa and the teeth. The recommendations 2.2, 2.3, 2.4, and 2.5 address this stimulatory approach.

If there is residual secretory capacity of the salivary glands, stimulation of natural saliva secretion may be provided by chewing or taste stimuli. This can be regular use of sugar-free lozenges, sugar-free candies, or sugar-free non-acidic chewing gum. In patients who have their natural teeth, it's important to be aware that if acidic candies are used to stimulate saliva secretion, then it should be a special nonerosive preparation for dentate patients that will say that they do not dissolve the tooth substance.

Pharmacological stimulation is also an option by prescription medication such as oral pilocarpine and cevimeline in countries where this is available. This may result in systemic adverse effects that limit use in some patients. So the gustatory and masticatory salivary reflex stimulation, Recommendation 2.2, the evidence-based quality was intermediate, and the strength of the recommendation was moderate.

And for the pharmacological stimulation by pilocarpine and cevimeline, it was evidence-based, high-quality, and strong recommendation strength. For patients who have salivary gland hypofunction or xerostomia induced by radiation therapy for head and neck cancer, stimulation of saliva secretion may also be provided by acupuncture, transcutaneous electrical stimulation, or acupuncture-like transcutaneous electrical stimulation, although the evidence base here is less strong than for the other stimulatory management options mentioned. This is addressed in Recommendation 2.4 and 2.5.

If the residual secretory capacity of the salivary glands is low or maybe even nonexistent, then regular lubrication of the oral mucosa and teeth is of relevance. This is addressed in Recommendation 2.1. Such lubrication may be provided by topical application of mucosal lubricants and saliva substitutes, which are agents directed at ameliorating xerostomia and other salivary gland hypofunction-related symptoms.

It is of importance to notice that available stimulatory and lubricating options all provide transitory increased salivary flow rates and transitory relief from xerostomia. If you would like to review the specific recommendations, they can be found in the manuscript.

BRITTANY HARVEY: Great. Thank you for reviewing those recommendations on the management of salivary gland hypofunction and/or xerostomia. So Dr. Peterson, you mentioned this earlier, but there are some cases in the guideline in which evidence was insufficient to make recommendations. And you went through a few of these areas. So what areas of future research did the panel discuss?

DR. DOUGLAS PETERSON: Thanks, Brittany. The panel worked very carefully to relate the quality of evidence to strength of each of the recommendations. In addition to providing important context regarding clinical prevention and treatment of xerostomia salivary hypofunction, novel directions for future research were therefore identified. And I'll just briefly delineate these future directions.

Studies directed to the continued, rapidly-evolving radiation technology such as proton therapy and volumetric modulated art therapy or VMAT, as well as the length of time after this treatment is completed, for example, one to five years after completion of treatment, these studies are needed to assess the relationship of this rapidly-evolving technology to the long-term adverse oral events such as salivary gland hypofunction and xerostomia as well as advanced dental disease and osteoradionecrosis as well.

Importantly, and the panel spent quite a bit of time deliberating this, ethical considerations must continue to be paramount in the study designs. And this is pertinent relative to this guideline. An important issue is that implementation of randomized clinical trials comparing current and novel radiation therapy modalities is typically precluded for ethical reasons. So this is a barrier to address, and the panel wanted to call attention to the scientific and clinical community.

In addition to the radiation technology itself, two additional future research directions also represent potential strategic advances in the field as well. First, radiosensitivity of parotid gland stem cells. For example, it has been recently shown that not all constituents of the parotid gland are equally radiosensitive because of an unequal distribution of the stem cells within the gland. This and related biologic concepts should be incorporated in future randomized controlled trials of head and neck cancer patients.

Secondly, novel regenerative medicine options may be used to spare, optimize, or restore salivary gland function after treatment. The guideline addresses these innovative treatment approaches in the context of both the current state of the science as well as opportunities for future research. I'll turn the microphone back to Brittany.

BRITTANY HARVEY: Great. Thank you, Dr. Peterson, for reviewing those areas where additional research would be helpful. So next, in your view, Dr. Mercadante, what is this guideline's importance and how will it affect clinicians?

DR. VALERIA MERCADANTE: Thank you for this question. We believe these guidelines offer an opportunity for any clinician involved in non-surgical cancer therapies-- oncologists, dentists, dental specialists, dental hygienists, oncology nurses, clinical researchers, advanced practitioners. We all have an essential role in supporting our patients for the entire journey by optimizing symptoms management and improve our patients quality of life.

These guidelines thus suggest a preventative and treatment course, but we've also delineated what we feel is common practice between experts and what areas would need further research to provide, as Dr. Peterson beautifully described, an ethical framework for future studies in this field.

BRITTANY HARVEY: Great. Thank you so much. So finally, Dr. Beier Jensen, how will these guideline recommendations impact patients?

DR. SIRI BEIER JENSEN: Well, for patients who live with these complications during cancer treatment or as [INAUDIBLE] of cancer therapies, these guideline recommendations on prevention and management of salivary gland hypofunction and xerostomia will enable them evidence-based and with the help of professional health care providers to support the natural functions of saliva and promote their oral comfort and health.

BRITTANY HARVEY: Great. Well, thank you all, Dr. Mercadante, Dr. Beier Jensen, and Dr. Peterson for taking the time to work on this guideline and produce evidence-based recommendations for clinicians and patients. And thank you for taking the time to speak with me today.

DR. BEIER JENSEN: Thank you.

DR. DOUGLAS PETERSON: Thank you.

BRITTANY HARVEY: And thank you to all of our listeners for tuning into the ASCO Guidelines podcast series. To read the full guideline, go to www.asco.org/supportive-care-guidelines. Additionally, our annual survey for guideline topics is open for submissions. Suggest a topic for guideline development at www.SurveyMonkey.com/r/ascoguidelinesurvey by August 1st. The link is also available in the episode notes of this podcast.

If you've enjoyed what you've heard today, please rate and review the podcast, and be sure to subscribe so you never miss an episode.

[MUSIC PLAYING]