Source: The Lancet Oncology

Radiation-related xerostomia has been the most significant and disabling side-effect of radiotherapy for head and neck cancer for more than 50 years. With the PARSPORT trial, reported in The Lancet Oncology, the largest and best designed of several randomised trials focusing on xerostomia, radiation oncologists and their partners in physics and dosimetry should take pride that significant progress has been made. Before the introduction of intensity-modulated radiotherapy (IMRT), more than 80% of survivors experienced substantial dry mouth syndrome and associated effects on dental health, swallowing, taste, and quality of life. By contrast, Nutting and colleagues report about 25% of 2-year survivors had significant clinician-rated xerostomia. Taken together with two randomised trials of IMRT for nasopharyngeal cancer, there is now compelling evidence of the power of advanced technology in reducing toxicity from head and neck radiotherapy.

Can even better use of technology help us to further reduce xerostomia? The parotid glands provide watery saliva during eating, which is largely replaceable by consuming more water or lubricants. The submandibular, sublingual, and minor salivary glands provide mucinous saliva, associated with the resting sense of moisture and dry mouth symptoms. Future work should systematically explore the prioritisation of different components of the salivary gland system. A clinical benefit from sparing the submandibular glands may be seen, beyond that seen by sparing the parotid glands. The mean dose delivered to the minor salivary glands within the oral cavity has also been reported to be a significant factor in patient-reported xerostomia. Further possibilities include gland repair or regenerative strategies with stem cells, acupuncture, or acupuncture-like stimulation. The promise of intensity-modulated protons provides even more optimism for reducing xerostomia and other acute and late effects.

Another important aspect of PARSPORT is the evolution of quantitative methods to assess xerostomia—eg, pre and post stimulation salivary flow, quality of life, clinical grading, and diet tolerance scales. While there is no agreement on which is the gold standard, we should use multiple measures which reflect different aspects and perspectives (patient clinician) on the issue. One must recognise an inherent weakness in technology-based xerostomia trials: neither patients nor clinicians are blinded. However, for those practicing radiotherapy for head and neck cancer, and for our patients, the improved outcomes are empirically obvious every day. Xerostomia is now an uncommon first complaint among survivors more than 3 months from treatment. This concern has been replaced by the next most bothersome issues: swallowing, taste, and fatigue. Reduction in the burden of treatment-related side-effects is especially important given the increasing number of patients presenting with oropharyngeal cancer (85% of patients in PARSPORT had disease at this site), related to the surge in cases of HPV infection. Considering the excellent prognosis of patients with oropharyngeal cancer with no or minimal smoking history (>80% 3-year survival), the potential for striking reductions in duration and magnitude of symptom burden is clear. Several ongoing studies are examining strategies to reduce treatment intensity for these patients, including radiation dose reduction, and substitution of cytotoxic drugs with targeted agents (eg, the recently approved RTOG-1016 for HPV-positive cancers).

Lastly, a recent report suggests that surgical relocation of a submandibular gland might be an effective way to reduce the sense of dry mouth at rest. This intervention can be applied anywhere surgeons are trained for this procedure, in collaboration with two-dimensional radiotherapy, and demands further investigation. Some of us may under-appreciate that IMRT technology is available to less than 10% of the global population. Salivary gland transfer thus may have a more immediate and long-term effect on the global burden of radiation-related xerostomia than all the beam modulation done for many decades.