Research from this year's Multidisciplinary Head and Neck Cancer Symposium focused on improving quality of life from the point of diagnosis through survivorship.
“We're curing many of these patients, which is great. But we're also realizing that with these cures, there's a lot of long-term dysfunction and morbidity that we have to deal with,” said, Ezra Cohen, MD, Co-Director of the Head and Neck Cancer Program at the University of Chicago Comprehensive Cancer Center, speaking in a telephone interview after the meeting. His poster study showed that early changes in the temperature of the mucosa may be able to predict which cancer patients will develop more severe mucositis than others (Abstract #122).
Although preliminary, the findings strongly suggest that the technology used—a highly sensitive camera that can detect minuscule temperature changes to about 0.10 C—will be an effective tool to detect the severity of this common side effect, Cohen said. “The changes would not be perceptible to the patient or physician, and we couldn't detect them with a regular thermometer or instrument.”
Slight increases in mucosa temperature early in treatment were seen in patients who went on to develop the more severe cases of mucositis. The researchers analyzed 35 locally advanced head and neck (oral cavity or oropharynx) cancer patients treated with a fluorouracil- and hydroxyurea-based chemoradiotherapy regimen and took temperature measurements before treatment began, and after 15, 30, 45, and 60 Gy of radiotherapy. Higher temperatures of the mucosa early on—before and immediately following the first treatment—were associated with more severe mucositis later on.
The heat detection camera used, which was developed at Argonne National Laboratory, works by detecting infrared light and generating an electrical signal that is then amplified and converted into digital data.
Nearly all patients with head and neck cancer treated with radiation or chemoradiation will develop some degree of mucositis, and about 60 percent develop grade 3 or 4, Cohen noted, adding that the rates of severe mucositis are increasing now that the standard treatment for this cancer type has become chemoradiation. “We accept the increased rate of toxicity because we're curing patients.”
Patients with grade 3 or 4 mucositis typically need nutritional support, and sometimes gastromy tubes (if swallowing becomes too difficult) and narcotic analgesic drugs, and may need to postpone cancer treatment until symptoms lessen.
But, predicting the severity of this side effect before cancer treatment starts could make it possible for steps to be taken to start treatment earlier to better support the patient. “There are chemotherapy agents that [produce a lesser] degree of mucositis. I may actually change the drug that I use concurrently with radiation to tailor the therapy to the individual patient.” Cohen explained.
Next steps, he said, would be larger and prospective studies.
IMRT Radiation Technique Improves Quality of Life
Allen Chen, MD, Assistant Professor and Residency Program Director at UC Davis Cancer Center, presented findings in a poster study that intensity-modulated radiation therapy (IMRT) improved quality of life among long-term survivors of head and neck cancer based on patients' self-reports in a poster presentation. The findings (Abstract #148) were also published in the International Journal of Radiation Oncology (doi:10.1016/j.ijrobp.2011.11.026).
“Until recently there was not a lot of clinical evidence suggesting that IMRT may be beneficial, despite the fact that the quality of the radiation plans on paper were so much superior,” said Chen, the study's lead author.”But, data such as ours, showing that IMRT significantly improves quality of life and a patient's functioning, supports its widespread use.”
After reviewing quality-of-life scores for 155 patients previously treated with radiation therapy for locally advanced head-and-neck cancer—all of whom were disease-free and had had at least two years of follow-up—Chen and his team found scores were higher in the patients treated with IMRT (84 patients) compared with those receiving traditional conformal radiotherapy (CRT) (71 patients) and actually improved over time.
One year after treatment, the proportion of IMRT-treated patients who rated global quality of life as “very good” or “outstanding” was 51% versus 41% in CRT-treated patients. And, two years after treatment those percentages increased to 73% for IMRT-treated patients and 49% for CRT-treated patients.
IMRT allows physicians to use computerized algorithms to designate how much radiation and to define limits for the radiation delivered to a tumor. “The computer uses this trade-off model to optimize delivery of radiation so that the tumor gets the maximum amount of radiation, and the surrounding critical structures, such as the brain, salivary tissues, the eyes, and the ears, all use the minimal amount,” Chen explained. “There's not a lot of conclusive evidence that the IMRT results in better curing, but these findings are demonstrating dramatic improvements in quality of life, which really support widespread use of IMRT.”
The researchers used the University of Washington Quality of Life questionnaire, which measures both health-related quality of life and global quality of life. The health-related quality-of-life measures for symptoms related to the cancer, including pain, appearance, swallowing, chewing, saliva, anxiety, and speech, and the global quality-of-life measures for both physical and mental health factors included family, friends, spirituality, and leisure activities. Using both measures was key because they reveal an overall level of global functioning, Chen said.
“Current treatments for head and neck cancer are really at the brink of tolerance levels for patients.” A key takeaway message is that researchers are starting to realize that. “Even though an increasing number of patients are being cured with intensified regimens and surgery, radiation, and chemotherapy, a lot of future research will be focused on potentially identifying ways of de-intensifying treatment so that long-term function can be improved.”
The most attractive reason for using IMRT therapy is the ability to spare the salivary glands, improve swallowing functions, and diminish the effects of long-term dry mouth, he said. “The data has become very clear that IMRT should become the standard of care.”
Adding Chemotherapy Helps Control Some Tumor Spread
Another study (Abstract #1) found that adding a chemotherapy regimen to the standard of care can improve local-regional tumor control in some head and neck cancer patients—a finding that could provide a significant benefit to managing tumors in this subset of patients, said Jay Cooper, MD, Director of the Cancer Center for Maimonides Medical Center. He reported that patients whose tumors had spread from the lymph glands into the surrounding soft tissue benefited from the addition of chemotherapy at a median follow-up of more than nine years, compared with the same subgroup of patients who had received just the standard of care—i.e., surgery plus radiation therapy. But, for those patients without tumor spread into those surrounding tissues, the added chemotherapy showed no benefit.
“For two different subgroups of a population, if you treated both groups either way—either all of them got chemo or all of them didn't—that really would be ideal for the entire group,” Cooper said in an interview.
The initial purpose of the study, a long-term follow-up of the Radiation Therapy Oncology Group 9501/Intergroup Phase III trial, was to examine the long-term outcomes of adding chemotherapy to the standard of care. But, the researchers found that even though overall survival rates stayed relatively constant despite the added chemotherapy, certain patients (those with tumor spread in the surrounding soft tissue of the head and neck) did benefit from the addition. “This takes us a little bit further down the road of personalized therapy,” he said.
The study tracked local-regional control of cancer spread in 410 high-risk resected head and neck cancer patients 10 years after treatment, separating out those who had received radiation therapy following surgery (RT: 60 Gy in 6 weeks) from those who had an identical radiation therapy regimen plus cisplatin (100 mg/m2 i.v. on days 1, 22, and 43) following surgery. There was no statistical difference in overall survival between the two groups.
But in the subgroup of patients who had microscopically involved resection margins and/or extracapsular spread of disease, local regional failure was more prevalent (33%) in patients not treated with chemotherapy compared with those given cisplatin in addition to the standard surgery plus radiation (21%).
PET Scan Proves Valuable in Recurrence Detection
Also at the meeting, a poster study presented by Yasir Rudha, MD, of St. John Hospital/Van Elslander Cancer Center found that positron emission tomography/computed tomography (PET/CT) scans were reliable in detecting local tumor recurrence in head and neck cancer patients (Abstract #226).
PET scanning is a relatively new test for detecting tumor recurrence, Rudha, the study's principal investigator said in a phone interview. But, these findings suggest the scans are a reliable detection method in follow-up care for head and neck cancer patients.
He and his co-researchers, from St. John Hospital and Medical Center and St. John Macomb/Oakland Hospital, analyzed 234 head and neck cancer patients first treated with chemotherapy and radiation, and given follow-up PET/CT scans. Of the 15 positive scans, 46% were false positives and 53% were true positives. But, all of the patients with negative scans remained disease-free according to the pathological records the researchers cross-referenced to confirm their results.
Rudha said the evidence showed PET scans accurately detected negative results—if no spread was detected on the scan, no further testing is needed. But, scans that did suggest tumor spread still had the potential to be false positives, so additional tests should be recommended.
He said that positive PET results could mean non-malignant inflammatory or physiological changes, or they could mean malignancy—local regional or distant recurrence—so additional confirmation such as MRI is needed.
The meeting is cosponsored by the American Head and Neck Society, the American Society of Clinical Oncology, the American Society for Radiation Oncology, and the Society of Nuclear Medicine.