Source: www.medscape.com
Author: Zosia Chustecka

In patients undergoing radiation treatment for head and neck cancer, reducing the radiation to organs not affected by cancer is key to improving quality of life post-treatment.

Several studies presented here at the 2014 Multidisciplinary Head and Neck Cancer Symposium described new approaches to sparing radiation delivered to the salivary glands and to the voice box, without any loss of cancer control, but with a reported reduction in adverse effects, such as xerostomia (dry mouth), and an anticipated reduction in loss of voice and speech quality.

Improvements in such outcomes are becoming increasingly important as the epidemiology of head and neck cancer is changing, and the increase in human papillomavirus-positive disease means that patients are being diagnosed their 50s and will, in many cases, go on to live for decades after their definitive cancer treatment, researchers commented at a press briefing.

Xerostomia can make it difficult to speak, as well as chew and swallow, and can lead to dental problems. “Dry mouth might seem trivial, but it actually has a significant effect on quality of life,” commented Tyler Robin, PhD, an MD candidate in his final year at the University of Colorado Medical School in Denver.

To reduce this adverse effect, intensity-modulated radiation techniques are already directing the beam away from the parotid gland, which is responsible for stimulated saliva production, for example during eating. But for the rest of the time, saliva is produced unstimulated from the submandibular gland. “This gland actually produces the majority of saliva for the majority of the day,” he said.

“Historically, however, there had been hesitation to spare the submandibular gland from radiation because there are lymph nodes near the gland that also end up not getting treated,” he said. “While this seems worrisome because head and neck cancer spreads through the lymph nodes, it is well established that the risk of cancer involvement in the lymph nodes near the submandibular gland is exceedingly low, yet the benefit of sparing the gland for a patient’s quality of life is high.”

Dr. Robin presented data from 71 patients with advanced head and neck cancer who were treated with radiation that spared the contralateral submandibular gland in a collaborative study conducted at the University of Colorado and the Memorial Sloan-Kettering Cancer Center in New York City. The mean radiation dose delivered to the contralateral gland was 33.04 Gy./p>

At a median follow-up of 27.3 months, none had had cancer recurrences in the spared area.

This is preliminary evidence that submandibular gland-sparing radiotherapy is feasible technically, and that it is safe even in advanced-stage node-positive cancers, the researchers conclude. They suggest that these outcomes data “offer significant promise for decreasing morbidity.”

More data on this submandibular gland-sparing approach were presented at the meeting by Moses Tam, BS, an MB candidate in his final year at New York University School of Medicine in New York City, who was also an author on the previous presentation.

He reported data from 125 patients (median age, 57 years) with oropharyngeal cancer (53% base of tongue, 41% tonsil, 6% other), all of whom had node involvement (16% N1, 8% N2A, 48% N2B, and 28% N2C).

All patients underwent chemoradiation, but some patients had sparing radiation, with a reduction of radiation treatment volume to the submandibular (level 1B) lymph nodes, while the remainder had radiation without sparing.

The sparing approach significantly reduced the dose of radiation to the submandibular salivary glands (from 70.5 Gy to 63.9 Gy in the ipsilateral gland, and from 56.2 Gy to 43.0 Gy in the contralateral gland), and also to the oral cavity (from 45.2 Gy to 36.1 Gy; all P < .001).

Both groups of patients had a similar 2-year local regional control rate — 97.5% with sparing radiation and 93.8% with nonsparing radiation — indicating a low rate of tumor recurrence at the original tumor site.

However, those who received the sparing radiation had significant improvement in both patient-reported xerostomia summary scores ( P = .021) and observer-rated xerostomia scores ( P = .006), compared with the other group.

“Our data show that it is safe to spare the lymph nodes in oropharyngeal cancer from radiation,” Tam commented. This approach reduces the radiation dose to several nearby salivary organs, and therefore causes less damage to a patient’s post-treatment salivary function.

Effects on Voice and Speech Under-recognized

In contrast to the attention that has been focused on chronic mouth dryness and swallowing difficulties as complications of radiotherapy, relatively little attention has been paid to treatment-related changes in voice and speech quality, commented Jeffrey Vainshtein, MD, chief resident in the Department of Radiation Oncology at the University of Michigan in Ann Arbor.

In fact, physicians tend to underestimate the detrimental effects of head and neck radiation on this aspect of patients’ quality of life, he commented, and presented data showing a wide discrepancy between the reports from patients as compared to physicians on a voice and speech quality assessment tool.

The finding comes from a study conducted in 91 patients with stage III or IV oropharyngeal cancer who had participated in trials at the University of Michigan and been treated with definitive concurrent chemotherapy (weekly carboplatin and paclitaxel) and organ-sparing intensity-modulated radiation therapy (IMRT).

Patient-reported results show a maximal decrease in voice and speech quality at 1 month, with 41% to 68% of patients (using 2 different questionnaires) reporting worse quality than pretreatment baseline levels. Voice and speech quality returned to baseline levels by 12 to 18 months, but not in all patients. At 12 months, 28% to 33% of patients continued to report lower voice and speech quality.

In contrast, physicians reported that larynx toxicity was rare, and reported grade 1 toxicity in 5% of patients at 6 months, and in none at 1 and 2 years.

“It’s interesting to see this physician and patient disconnect,” commented Mitchell Machtay, MD, chair of radiation oncology at Case Western Reserve University in Cleveland, who moderated the press conference.

Dr. Vainshtein said that the degree of disconnect was “quite surprising,” but added that this is not unique to this study or to oncology, and indeed is seen throughout medicine. He suggested that physicians may miss the subtleties of changes in quality of life, and also some patients may not mention symptoms when talking with their doctor, but once they are asked in detail in a structured questionnaire, the results can be quite informative. He also said that more emphasis should be, and in fact is already being, placed on patient-reported outcomes in clinical trials.

Further analysis showed that the mean radiation dose to the voice box (glottic larynx) was independently associated with poor voice quality, while patient-perceived speech difficulties were related to the radiation dose received by both the voice box and the oral cavity.

These findings, from the largest prospective study of this issue to date, support limiting the mean radiation dose to the glottic larynx to less than 20 Gy during whole-neck IMRT for head and neck cancer when the larynx is not a target, the researchers conclude.

Minimizing the radiation dose is likely to reduce voice and speech problems, and thus improve post-treatment quality of life, Dr. Vainshtein commented.

Notes: The authors have disclosed no relevant financial relationships.
Source: 2 2014 Multidisciplinary Head and Neck Cancer Symposium (MHNCS): Abstracts 12 (Robin), 121 (Vainshtein), 139 (Tam). Presented February 21, 2014.

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