Quality-of-life (QOL) concerns were front and center in the research reported at the Multidisciplinary Head and Neck Cancer Symposium. That common theme, noted Mitchell Machtay, MD, Chairman of the Department of Radiation Oncology at University Hospitals Case Medical Center, the moderator of a news conference during the meeting, “shows the increased importance that we as physicians and the cancer care team are placing on quality of life, patient-reported outcomes, and [what is sometimes a] disconnect between how physicians and patients themselves assess side effects.”
Daily Humidification Reduces Mucositis
One of the meeting's plenary studies reported that patients who underwent daily humidification of the mouth and throat region spent nearly 50 percent fewer days in the hospital to manage side effects (Abstract 2).
The randomized, prospective study included 210 patients with head and neck cancers who received institutional standard of care or underwent humidification for at least four hours daily (from the start of treatment for 12 weeks) using at-home devices (provided to the patients), which could be worn during sleep or other sedentary activities throughout the day (see photo below).
The high-flow rate devices deliver humidified air through the nose via a plastic nasal interface, providing more vaporized moisturization than would be possible without the device, the study's lead author, Andrew Macann, MBcHB, a radiation oncologist at Auckland City Hospital in New Zealand, explained at the news briefing.
Patients who underwent daily humidification (for at least four hours a day) on average spent 2.3 days in the hospital to manage side effects compared with 4.1 days for patients who received standard cares.
Patients using the humidifiers had clinical mucositis scores that were similar to those for patients in the control group (8.25 versus 8.38, respectively), according to the Common Terminology Criteria Adverse Events (CTCAE) version 3.0 measure (in the intention-to-treat analysis)—but patients using humidifiers (for at least four hours a day, those compliant with the protocol) did have reduced functional mucositis scores (6.7 versus 8.6 for patients in the control group receiving standard care).
Macann noted that despite the score being a primary endpoint of the study, inter-observer variation in reporting those scores (which are based on the clinician's observation of the degree of ulceration in the mouth and throat) makes it less reliable to detect accurate signals of mucositis compared with functional mucositis scores (a clinician-reported outcome based on the patient's symptom burden)—and in fact, that clinical mucositis score is no longer an endpoint in the more recent version of the CTCAE.
Other findings (seen across clinician-reported, patient-reported, and independent outcomes) were that, compared with patients receiving standard care, patients using the humidifiers also:
* Returned to normal eating patterns sooner (at 20 weeks, clinician-reported Nutritional Mode scores were 5.23 on average for patients in the humidification arm vs. 4.8 for the control arm);
* Were less likely to require a feeding tube (85 percent of patients in the humidification arm never required a feeding tube vs. 73 percent in the control arm); and
* Tended to report less symptom severity on the Head and Neck Radiotherapy Questionnaire (although most times those points did not reach significance).
The report also found, however, that of the patients assigned to use the humidifiers daily at the start of the trial, only 42 percent met the defined benchmark of compliance (using the device for at least four hours daily)—only those patients who did meet that benchmark were included in the results reported for that arm of study. (On average, compliant patients used the humidifier for 7.2 hours per day, whereas non-compliant patients used the humidifiers for only one hour per day.)
The compliance issues were similar to compliance issues seen with other supportive therapies—and the next step of this work, Macann noted, is determining how to increase the number of patients who use the devices effectively.
Sparing Techniques in Chemoradiation
Other QOL studies reported at the meeting focused on using sparing techniques during treatment. For patients with head and neck cancer undergoing radiation therapy, reducing the amount of radiation treatment volume to the submandibular (level IB) lymph nodes resulted in better patient-reported salivary function, and yielded good local regional disease control, one study found (Abstract 139).
“Sparing these structures was safe and did not compromise outcomes,” the study's lead author, Moses Tam, an MD candidate in his final year at New York University School of Medicine, said during a news briefing. “These patients have dry mouth throughout the day and need to use water bottles to keep the mouth moist. In more severe cases patients have difficulty swallowing food.”
The retrospective study analyzed 125 patients with node-positive oropharyngeal cancer who received chemoradiation, categorized as either having received sparing radiation (which reduced the treatment volume to the region with bilateral level IB nodes) (40 patients), or non-sparing treatment (85 patients).
All patients had lymph node involvement (16% were N1, 8% were N2A, 48% were N2B, and 28% were N2C). And, 74 percent of patients had T1–2 disease and 26 percent had T3–4 disease.
The patients who received treatment with sparing reported significantly improved xerostomia summary scores, compared with patients who received treatment without sparing; and observer-rated xerostomia scores for those patients were also improved.
The two-year local regional control rate for the group who received treatment with sparing was 97.5 percent versus 93.8 percent for the group who received treatment without sparing, which the researchers noted indicates a low rate of cancer recurrence for all patients at the original tumor site.
Also, dosimetric analyses of the patients' salivary glands showed that the mean radiation dose to the mouth and neck regions (including the ipsilateral submandibular gland, the contralateral submandibular gland, and the oral cavity) of the patients who had received sparing treatment was lower than the scores of patients in the group who had not received sparing treatment, as was expected, indicating that sparing therapy did decrease the dose of radiation to the areas that were intended to be spared.
Avoiding Contralateral Submandibular Gland in Advanced Disease
Another study found that for patients with advanced node-positive head and neck cancers, including base of tongue 9 lesions, avoiding the contralateral submandibular gland during radiation therapy is feasible and safe—which significantly reduced dry mouth (Abstract 12).
Sparing the submandibular gland during radiation is a technique that has been shown to be safe and effective for patients with earlier-stage cancers, Tyler Robin, PhD, an MD candidate in his final year at the University of Colorado School of Medicine, said during a news briefing.
“The point of the study was to look at these locally advanced cancers where there is more concern that there might be spread to those lymph nodes—and even in these locally advanced cancers, it was still safe to do this practice.”
The researchers retrospectively analyzed 71 patients who received radiation for head and neck cancers to the bilateral neck that spared the contralateral submandibular gland: 40 patients having been treated for primary tonsil cancers and 31 for tumors involving the base of the tongue. Approximately 80 percent of patients had cancer that had spread to at least two lymph nodes (N2b) or greater disease, and 90 percent had overall stage IV disease. The median age of the patients was 55, and approximately 50 percent were current or former smokers.
They found that no patients experienced recurrence in the contralateral level IB lymph nodes, the area of the spared submandibular gland, at a median follow-up of 27.3 months. The mean radiation dose to the contralateral submandibular gland was 33.04 Gy (Robin noted that the gland can be spared with doses less than 39 Gy).
He said the study provides solid preliminary evidence that clinicians should consider the sparing technique in appropriate patients, but that a large, prospective randomized trial, of course, is still needed.
Limiting RT to Glottis Larynx Improves Voice & Speech
Also reported at the meeting, limiting the radiation dose to the glottis larynx for patients with oropharyngeal cancer was found to decrease post-treatment voice and speech quality problems (Abstract 121).
Relatively little attention has been directed to treatment-related changes in voice and speech quality, compared with other treatment side effects like dry mouth and swallowing, the study's lead author, Jeffrey Vainshtein, MD, Chief Resident in the Department of Radiation Oncology at the University of Michigan, explained in an email after the meeting.
These data show a clear relationship between the radiation dose to the voice box and the likelihood of patients reporting worsening voice quality, as well as between the time to treatment and the likelihood of patients reporting worsening of voice quality, he said. “By asking our patients not just, ‘how are you feeling? but also specifically, ‘how is your voice?’—in this more structured patient-reported outcomes format—we are going to flesh out some of these more nuanced details.”
The retrospective analysis included 91 patients with stage III or IV oropharyngeal cancer treated with combined chemotherapy and radiation that used intensity-modulated radiation therapy to minimize the radiation dose to the pharyngeal constrictors, salivary glands, oral cavity, glottic larynx, supraglottic larynx, and esophagus.
Patient-reported voice quality worsening was closely related to the radiation dose received by the glottic larynx, and patient-reported speech difficulty was related to the radiation dose received by both the glottic larynx and oral cavity.
Compared with the pre-treatment University of Michigan Head and Neck Quality of Life questionnaire (HNQOL-C) scores, at six months post-treatment: 25 percent of the patients who received a radiation dose of less than 20 Gy to the glottic larynx reported worse HNQOL-C scores; as did 33 percent of patients who received 20 to 30 Gy; 59 percent of patients who received 30 to 40 Gy; 50 percent of patients who received 40 to 50 Gy; and 64 percent of patients who received more than 50 Gy.
And at 12 months post-treatment (compared with pre-treatment HNQOL-C scores): 10 percent of patients who received less than 20 Gy to the glottic larynx reported worse HNQOL-C scores; as did 32 percent of patients receiving 20 to 30 Gy, 25 percent of patients receiving 30 to 40 Gy, 30 percent of patients receiving 40 to 50 Gy; and 63 percent of patients receiving more than 50 Gy.
Additionally, the findings showed:
* The highest percentage of patients reported a decrease in voice and speech quality at one month post-treatment (68% of patients reporting worsening using the HNQOL-C, and 41% reporting worsening using the University of Washington Quality of Life questionnaire [UWQOL-S]);
* At 12 months after treatment, fewer patients continued to report a decrease in voice and speech quality (33% using the HNQOL-C and 28% using the UWQOL-S); and
* Patients reported more adverse effects from treatment for voice and speech quality compared with independent physician assessment—physicians reported grade one or higher toxicity in five percent of patients at three months post-treatment and in none of the patients at one and two years post-treatment.
“Our findings highlight the critical role of patient-reported outcomes in identifying areas of improvement for current therapies, which may go under-recognized strictly by physician-reporting of common toxicities,” Vainshtein said.
Toxicities Underreported & Underemphasized
As these researchers and others have identified, physician-graded assessments of toxicities do not consistently match with patient-reported outcomes, Machtay said in an email after the meeting. “We must be mindful of this. Most clinicians would not consider these late side effects to be ‘trivial,’ but indeed they are underreported and underemphasized in the medical literature.”
Asked to comment for this article, Prabhakar Tripuraneni, MD, a radiation oncologist at Scripps Clinic, said head and neck cancer side effects need be addressed because they are so prevalent and so “life-taxing.”
“These are the day-to-day faculties—communication, eating, moisture in the mouth—that are essential to function.” And, one of the difficulties, he noted, is the lack of tools to measure symptoms like loss of quality of voice or loss of moisture in the mouth: “What the patient perceives seems to be a lot more than what we can accurately measure.”
Tripuraneni called the humidification study by Macann et al “remarkable.”
“The technique is not invasive, and does not alter the radiation therapy to the patient. We still have some work to do—40 percent of these patients had difficulty maintaining the amount of humidity. But, at the same time, I'm going to use this in my clinic tomorrow. It's cost-effective; I'm not compromising or cutting back on treatments; and the data show the patients are benefitting. And even if they're not going to benefit, you haven't really lost anything in trying.”
The other three studies (by Tam, Robin, and Vainshtein) are important because they address one of the biggest challenges facing head and neck cancer today, Tripuraneni continued. “We are reaching a plateau of where we can get [in terms of improving cure rates]. The challenge is what is the least we can do for head and neck cancer patients to still maintain that cure rate, but so that we can improve quality of life.”
The Multidisciplinary Head and Neck Cancer Symposium, which this year had 189 abstracts, was co-sponsored by the American Society for Radiation Oncology, the American Society of Clinical Oncology, and the American Head & Neck Society.