Jeffrey E. Terrell

QUALITY OF LIFE AFTER PAROTID-SPARING IMRT FOR HEAD-AND- NECK CANCER: A PROSPECTIVE LONGITUDINAL STUDY

PURPOSE Parotid-sparing intensity-modulated radiotherapy (IMRT) for head-and-neck cancer reduces xerostomia compared with standard RT. To assess potential improvements in broader aspects of quality of life (QOL), we initiated a study of patient-reported QOL and its predictors after IMRT. MATERIALS AND METHODS This was a prospective longitudinal study of head-and-neck cancer patients receiving multisegmental static IMRT. Patients were given a validated xerostomia questionnaire (XQ), and a validated head-and-neck cancer-related QOL questionnaire consisting of four multi-item domains: Eating, Communication, Pain, and Emotion. The Eating domain contains one question (total of six) asking directly about xerostomia. In both questionnaires, higher scores denote worse symptoms or QOL. The questionnaires and measurements of salivary output from the major glands were completed before RT started (pre-RT) and at 3, 6, and 12 months after RT. The association between the QOL scores and patient-, tumor-, and therapy-related factors was assessed using the random effects model. RESULTS Thirty-six patients participating in the study completed the questionnaires through 12 months. The XQ scores worsened significantly at 3 months compared with the pre-RT scores, but later they improved gradually through 12 months (p = 0.003), in parallel with an increase in the salivary output from the spared salivary glands. The QOL summary scores were stable between the baseline (pre-RT) and 3 months after RT scores. Patients receiving postoperative RT (whose pre-RT questionnaires were taken a few weeks after surgery) tended to have improved scores after RT, reflecting the subsidence of acute postoperative sequelae, compared with a tendency toward worsened scores in patients receiving definitive RT. After 3 months, statistically significant improvement was noted in the summary QOL scores for all patients, through 12 months after RT (p = 0.01). The salivary flow rates, tumor doses, mean oral cavity dose, age, gender, sites or stages of tumor, surgery, and use of chemotherapy were not associated with the QOL scores at any point. The mean dose to the parotid glands correlated with the QOL scores at 3 months (p = 0.05) but not at other post-RT periods. The XQ and QOL summary scores did not correlate before RT but were significantly correlated at each post-RT point (p < 0.01), with a linear correlation coefficient (r) of 0.59, 0.72, and 0.67 at 3, 6, and 12 months, respectively. At these points, the XQ scores also correlated significantly with the scores of each of the individual QOL domains (p < or = 0.01), including the domains Pain and Emotion, which did not contain any xerostomia-related question. CONCLUSION After parotid-sparing IMRT, a statistically significant correlation was noted between patient-reported xerostomia and each of the domains of QOL: Eating, Communication, Pain, and Emotion. Both xerostomia and QOL scores improved significantly over time during the first year after therapy. These results suggest that the efforts to improve xerostomia using IMRT may yield improvements in broad aspects of QOL.

Parotid gland sparing in patients undergoing bilateral head and neck irradiation: Techniques and early results.

PURPOSE To minimize xerostomia in patients receiving bilateral head and neck irradiation (RT) by using conformal RT planning to spare a significant volume of one parotid gland from radiation. METHODS AND MATERIALS The study involved 15 patients with head and neck tumors in whom bilateral neck radiation was indicated. The major salivary glands and the targets (tumor, surgical bed, metastases to lymph nodes, and the locations of lymph nodes at risk for metastases) were outlined on axial computed tomography images. Beams-eye view (BEV) displays were used to construct conformal beams that delivered the prescribed doses to the targets while sparing from direct radiation most of one parotid gland. The gland that was planned to be spared resided in the neck side that was judged in each patient to be at a lesser risk of metastatic disease. Major salivary gland flow rates and the responses to a subjective xerostomia questionnaire were assessed before, during, and after radiation. RESULTS Radiation planning for patients with central oropharyngeal tumors required the generation of multiple axial nonopposed beams. The resulting isodoses encompassed the targets, including the retropharyngeal nodes and the jugular nodes up to the base of skull bilaterally, while limiting the dose to the oral cavity, spinal cord, and one parotid gland. For patients with lateralized tumors, the ipsilateral neck side was treated up to the base of the skull; in the contralateral neck side, the treatment included the subdigastric nodes but excluded the jugular nodes at the base of the skull and most of the parotid gland. This was accomplished by a moderate gantry angle that was chosen using the BEV displays. Three months following the completion of radiation, the spared parotid glands retained on average 50% of their unstimulated and stimulated flows. In contrast, no saliva flow was measured from the unspared glands in any of the patients. Subjective xerostomia was absent, mild, or not different from that reported before radiation in 10 of 15 patients (67%). CONCLUSION Partial parotid gland sparing is feasible by using three-dimensional planning in patients undergoing bilateral head and neck radiation. Approximately 50% of the saliva flow from the spared glands may be retained, and most patients thus treated have no or mild xerostomia in the early period after the completion of radiation. Whether tumor control and late complications are comparable to standard radiation will be assessed as more experience is gained.

Interleukin‐6 predicts recurrence and survival among head and neck cancer patients

Increased pretreatment serum interleukin (IL)‐6 levels among patients with head and neck squamous cell carcinoma (HNSCC) have been shown to correlate with poor prognosis, but sample sizes in prior studies have been small and thus unable to control for other known prognostic variables.

Pain, Quality of Life, and Spinal Accessory Nerve Status After Neck Dissection

Objective To assess quality of life (QOL) in patients with head and neck cancer who underwent neck dissection and to compare QOL scores for patients in whom the spinal accessory nerve (CN XI) was resected or preserved.

Salivary Gland Sparing and Improved Target Irradiation by Conformal and Intensity Modulated Irradiation of Head and Neck Cancer

The goals of this study were to facilitate sparing of the major salivary glands while adequately treating tumor targets in patients requiring comprehensive bilateral neck irradiation (RT), and to assess the potential for improved xerostomia. Since 1994 techniques of target irradiation and locoregional tumor control with conformal and intensity modulated radiation therapy (IMRT) have been developed. In patients treated with these modalities, the salivary flow rates before and periodically after RT have been measured selectively from each major salivary gland and the residual flows correlated with glands’ dose volume histograms (DVHs). In addition, subjective xerostomia questionnaires have been developed and validated. The pattern of locoregional recurrence has been examined from computed tomography (CT) scans at the time of recurrence, transferring the recurrence volumes to the planning CT scans, and regenerating the dose distributions at the recurrence sites. Treatment plans for target coverage and dose homogeneity using static, multisegmental IMRT were found to be significantly better than standard RT plans. In addition, significant parotid gland sparing was achieved in the conformal plans. The relationships among dose, irradiated volume, and the residual saliva flow rates from the parotid glands were characterized by dose and volume thresholds. A mean radiation dose of 26 Gy was found to be the threshold for preserved stimulated saliva flow. Xerostomia questionnaire scores suggested that xerostomia was significantly reduced in patients irradiated with bilateral neck, parotid-sparing RT, compared to patients with similar tumors treated with standard RT. Examination of locoregional tumor recurrence patterns revealed that the large majority of recurrences occurred inside targets, in areas that had been judged to be at high risk and that had received RT doses according to the perceived risk. Tangible gains in salivary gland sparing and target coverage are being achieved, and an improvement in some measures of quality of life is suggested by our findings. Additional reduction of xerostomia may be achieved by further sparing of the salivary glands and the non-involved oral cavity. A mean parotid gland dose of ≤ 26 Gy should be a planning objective if significant parotid function preservation is desired. The pattern of recurrence suggests that careful escalation of the dose to areas judged to be at highest risk may improve tumor control.

Effect of smoking, alcohol, and depression on the quality of life of head and neck cancer patients

This pilot study examined the relationship between smoking, alcohol intake, depressive symptoms and quality of life (QoL) in head and neck cancer patients. A questionnaire on smoking, alcohol, depressive symptoms and QoL was distributed to head and neck cancer patients (N=81). Over one-third (35%) of the respondents had smoked within the last 6 months, 46% had drunk alcohol within the last 6 months and 44% screened positive for significant depressive symptoms. About one-third (32%) of smokers were interested in smoking cessation services and 37% of patients with depressive symptoms were interested in depression services. However, only 9% of those who drank alcohol expressed interest in alcohol services. Smoking was negatively associated with five scales of the SF-36V including Physical Functioning, General Health, Vitality, Social Functioning, and Role-Emotional Health. Depressive symptoms were negatively associated with all eight scales on the SF-36V and all four scales of the Head and Neck Quality of Life instrument. Surprisingly, alcohol was not found to be associated with any of the QoL scales. While smoking, alcohol intake and depression may be episodically treated, standardized protocols and aggressive intervention strategies for systematically addressing these highly prevalent disorders are needed in this population.

Radiation Concurrent With Gemcitabine for Locally Advanced Head and Neck Cancer: A Phase I Trial and Intracellular Drug Incorporation Study

PURPOSE To examine the feasibility and dose-limiting toxicity (DLT) of once-weekly gemcitabine at doses predicted in preclinical studies to produce radiosensitization, concurrent with a standard course of radiation for locally advanced head and neck cancer. Tumor incorporation of gemcitabine triphosphate (dFdCTP) was measured to assess whether adequate concentrations were achieved at each dose level. PATIENTS AND METHODS Twenty-nine patients with unresectable head and neck cancer received a course of radiation (70 Gy over 7 weeks, 5 days weekly) concurrent with weekly infusions of low-dose gemcitabine. Tumor biopsies were performed after the first gemcitabine infusion (before radiation started), and the intracellular concentrations of dFdCTP were measured. RESULTS Severe acute and late mucosal and pharyngeal-related DLT required de-escalation of gemcitabine dose in successive patient cohorts receiving dose levels of 300 mg/m(2)/wk, 150 mg/m(2)/wk, and 50 mg/m(2)/wk. No DLT was observed at 10 mg/m(2)/wk. The rate of endoscopy- and biopsy-assessed complete tumor response was 66% to 87% in the various cohorts. Tumor dFdCTP levels were similar in patients receiving 50 to 300 mg/m(2) (on average, 1.55 pmol/mg, SD 1.15) but were barely or not detectable at 10 mg/m(2). CONCLUSION A high rate of acute and late mucosa-related DLT and a high rate of complete tumor response were observed in this regimen at the dose levels of 50 to 300 mg/m(2), which also resulted in similar, subcytotoxic intracellular dFdCTP concentrations. These results demonstrate significant tumor and normal tissue radiosensitization by low-dose gemcitabine. Different regimens of combined radiation and gemcitabine should be evaluated, based on newer preclinical data promising an improved therapeutic ratio.

A Tailored Smoking, Alcohol, and Depression Intervention for Head and Neck Cancer Patients

Background: Smoking, alcohol use, and depression are interrelated and highly prevalent in patients with head and neck cancer, adversely affecting quality of life and survival. Smoking, alcohol, and depression share common treatments, such as cognitive behavioral therapy and antidepressants. Consequently, we developed and tested a tailored smoking, alcohol, and depression intervention for patients with head and neck cancer. Methods: Patients with head and neck cancer with at least one of these disorders were recruited from the University of Michigan and three Veterans Affairs medical centers. Subjects were randomized to usual care or nurse-administered intervention consisting of cognitive behavioral therapy and medications. Data collected included smoking, alcohol use, and depressive symptoms at baseline and at 6 months. Results: The mean age was 57 years. Most participants were male (84%) and White (90%). About half (52%) were married, 46% had a high school education or less, and 52% were recruited from Veterans Affairs sites. The sample was fairly evenly distributed across three major head and neck cancer sites and over half (61%) had stage III/IV cancers. Significant differences in 6-month smoking cessation rates were noted with 47% quitting in the intervention compared with 31% in usual care (P < 0.05). Alcohol and depression rates improved in both groups, with no significant differences in 6-month depression and alcohol outcomes. Conclusion: Treating comorbid smoking, problem drinking, and depression may increase smoking cessation rates above that of usual care and may be more practical than treating these disorders separately. (Cancer Epidemiol Biomarkers Prev 2006;15(11):2203–8)

Quality of Life Scores Predict Survival Among Patients With Head and Neck Cancer

PURPOSE The purpose of this study was to examine whether quality of life (QOL) scores predict survival among patients with head and neck cancer, controlling for demographic, health behavior, and clinical variables. PATIENTS AND METHODS A self-administered questionnaire was given to 495 patients being treated for head and neck cancer while they were waiting to be seen for a clinic appointment. Data collected from the survey included demographics, health behaviors, and QOL as measured by Short Form-36 (SF-36) physical and mental component scores and the Head and Neck QOL scores. Clinical measures were collected by chart abstraction. Kaplan-Meier plots and univariate and multivariate Cox proportional hazards models were used to determine the association between QOL scores and survival time. RESULTS After controlling for age, time since diagnosis, marital status, education, tumor site and stage, comorbidities, and smoking, the SF-36 physical component score and three of the four Head and Neck QOL scales (pain, eating, and speech domains) were associated with survival. Controlling for the same variables, the SF-36 mental component score and the emotional domain of the Head and Neck QOL were not associated with survival. CONCLUSION QOL instruments may be valuable screening tools to identify patients who are at high risk for poor survival. Those with low QOL scores could be followed more closely, with the potential to identify recurrence earlier and perform salvage treatments, thereby possibly improving survival for this group of patients.

Functional assessment using Constant's Shoulder Scale after modified radical and selective neck dissection.

Constants Shoulder Scale is a validated and widely applied instrument for assessment of shoulder function. We used this instrument to assess which treatment and demographic variables contribute to shoulder dysfunction after neck dissection in head and neck cancer patients.