Feasibility and value of salivary cortisol sampling to reflect distress in head and neck cancer patients undergoing chemoradiation: A proof-of-concept study.

Background: Head and neck cancer (HNC) patients undergoing chemo/radiation commonly experience severe and persistent distress associated with treatment related fear and physical side effects such as xerostomia, dysphagia, and dryness of mouth. Cortisol, a stress sensitive hormone, can be easily measured in saliva to reflect biobehavioral responses to such stressors. Unfortunately, it has not been used in this population due to concerns associated with chemoradiation (C/RT) related xerostomia. Methods: In a proof-of-concept study, we explored the feasibility of collecting salivary cortisol as a marker of fear and distress in HNC patients. Ten HNC subjects undergoing C/RT provided saliva samples for 3 consecutive days across three timepoints (pre-treatment, 3-weeks and 1-month post-treatment) and completed concurrent depression, anxiety and swallowing related fear measures. Results: Salivary cortisol collection adherence was between 80-60%. It was not impacted by xerostomia. Diurnal cortisol pattern demonstrated dysregulation at pretreatment in 62%, and flattened aberrant slopes continued at 3-weeks and beyond in 50% of subjects. Conclusions: Our study supports the feasibility and utility of salivary cortisol measurement in HNC patients across the treatment trajectory. Diurnal cortisol measures may be a valuable tool to detect and monitor treatment distress during C/RT in this population.

Emotional disclosure and cognitive processing in couples coping with head and neck cancer.

Head and neck cancer (HNC) patients and their spouses experience communication problems and high rates of emotional distress. Couple-based interventions that encourage emotional disclosure hold promise for improving cognitive processing and distress in this population, but more research needs to examine when and for whom emotional disclosure is an effective coping strategy. In this observational study, 125 HNC patients (83% male) and their spouses were videotaped discussing a cancer-related concern in the laboratory. Discussions were coded with the specific affect coding system. Actor-partner interdependence models showed that patient expression of negative emotions (i.e., disdain, contentiousness, distress) was not related to his/her own or the spouse's cognitive processing (assessed as reaction times to cancer and noncancer words on a computerized cognitive task administered immediately following the discussion). When spouses expressed support (e.g., interest, validation), they had better cancer- (effect size r = - 0.21) and noncancer-related cognitive processing (r = - 0.17), but patients did not. However, when spouses expressed disdain (e.g., contempt) and contentiousness (e.g., criticism, domineering), patients had poorer cancer- (r = 0.20-0.22) and noncancer-related cognitive processing (r = 0.19-0.26). Findings suggest consideration of the valence of affective expression and which partner is disclosing/listening before unilaterally encouraging HNC couples to openly express emotions as a means of alleviating distress.

Dyadic Coping in Patients Undergoing Radiotherapy for Head and Neck Cancer and Their Spouses.

Background: Head and neck cancer (HNC) adversely affects the psychological (i.e., depression, anxiety) and marital adjustment of patients and their spouses. Dyadic coping refers to how couples cope with stress. It includes positive actions like sharing practical or emotional concerns (i.e., problem- and emotion-focused stress communication; PFSC, EFSC), and engaging in problem- or emotion-focused actions to support each other (problem- and emotion-focused dyadic coping; PFDC, EFDC). It also includes negative actions like avoidance (negative dyadic coping; NEGDC). In this secondary analysis of a randomized pilot trial of a couple-based intervention called SHARE (Spouses coping with the Head And neck Radiation Experience), we first examined associations between patients' and spouses' dyadic coping (and satisfaction with dyadic coping; SATDC) and their own/each other's psychological and marital adjustment. Next, we examined the effects of SHARE relative to usual medical care (UMC) on patients' and spouses' dyadic coping. Finally, we examined whether changes in dyadic coping were associated with changes in patients' and spouses' psychological and marital adjustment. Methods and Measures: Thirty HNC patients (80% men) and their spouses (N = 60) completed baseline surveys prior to initiating radiotherapy (RT) and were randomized to SHARE or UMC. One month after RT, they completed follow-up surveys. Results: Baseline multilevel Actor-Partner Interdependence Models revealed significant actor effects of PFSC (effect size r = -0.32) and PFDC (r = -0.29) on depression. For marital adjustment, significant actor effects were found for PFSC, PFDC, EFDC, and SATDC (p < 0.05, r = 0.23 to 0.38). Actor (r = -0.35) and partner effects (r = -0.27) for NEGDC were also significant. Moderate to large effect sizes were found in favor of SHARE on PFSC (Cohen's d = 1.14), PFDC (d = 0.64), NEGDC (d = -0.68), and SATDC (d = 1.03). Improvements in PFDC were associated with reductions in depression and anxiety (p < 0.05); and, improvements in SATDC were associated with improvements in anxiety and marital adjustment (p < 0.05). Conclusion: The SHARE intervention improved positive and decreased negative dyadic coping for patients and spouses. Increases in positive dyadic coping were also associated with improvements in psychological and marital adjustment. Although findings are preliminary, more research on ways to integrate dyadic coping into oncology supportive care interventions appears warranted.

Factors Associated With Radiation Treatment Compliance for Women With Cervical Cancer in a Safety Net Health System.

OBJECTIVE: The aim of the study was to determine whether patient characteristics are associated with radiation treatment noncompliance. METHODS/MATERIALS: We retrospectively studied 244 patients with cervical cancer treated with chemoradiation between May 2006 and August 2015 at a safety net health center. Compliance with treatment was defined as missing less than 2 days of scheduled radiation. RESULTS: Treatment records revealed a compliance rate of 50.8% in this population. Factors associated with noncompliance were younger age (hazard ratio [HR], 1.037; P = 0.004), presence of psychiatric diagnosis (HR, 0.581; P = 0.044), and having insurance (HR, 0.484; P = 0.022). Noncompliance was associated with a decrease in disease-free survival (HR, 0.555; P = 0.042) but was not associated with overall survival. International Federation of Gynecology and Obstetrics stage was associated with detriment in overall survival on multivariate analysis (HR, 2.034; P = 0.001). CONCLUSIONS: Younger patients, those with psychiatric illness, and those with insurance define a group that is more likely to be noncompliant with treatment and hence may require up-front intervention to improve outcomes.

Parotid gland dose in intensity-modulated radiotherapy for head and neck cancer: is what you plan what you get?

PURPOSE: To quantify the differences between planned and delivered parotid gland and target doses, and to assess the benefits of daily bone alignment for head and neck cancer patients treated with intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS: Eleven head and neck cancer patients received two CT scans per week with an in-room CT scanner over the course of their radiotherapy. The clinical IMRT plans, designed with 3-mm to 4-mm planning margins, were recalculated on the repeat CT images. The plans were aligned using the actual treatment isocenter marked with radiopaque markers (BB) and bone alignment to the cervical vertebrae to simulate image-guided setup. In-house deformable image registration software was used to map daily dose distributions to the original treatment plan and to calculate a cumulative delivered dose distribution for each patient. RESULTS: Using conventional BB alignment led to increases in the parotid gland mean dose above the planned dose by 5 to 7 Gy in 45% of the patients (median, 3.0 Gy ipsilateral, p = 0.026; median, 1.0 Gy contralateral, p = 0.016). Use of bone alignment led to reductions relative to BB alignment in 91% of patients (median, 2 Gy; range, 0.3-8.3 Gy; 15 of 22 parotids improved). However, the parotid dose from bone alignment was still greater than planned (median, 1.0 Gy, p = 0.007). Neither approach affected tumor dose coverage. CONCLUSIONS: With conventional BB alignment, the parotid gland mean dose was significantly increased above the planned mean dose. Using daily bone alignment reduced the parotid dose compared with BB alignment in almost all patients. A 3- to 4-mm planning margin was adequate for tumor dose coverage.

Reduce in variation and improve efficiency of target volume delineation by a computer-assisted system using a deformable image registration approach.

PURPOSE: To determine whether a computer-assisted target volume delineation (CAT) system using a deformable image registration approach can reduce the variation of target delineation among physicians with different head and neck (HN) IMRT experiences and reduce the time spent on the contouring process. MATERIALS AND METHODS: We developed a deformable image registration method for mapping contours from a template case to a patient case with a similar tumor manifestation but different body configuration. Eight radiation oncologists with varying levels of clinical experience in HN IMRT performed target delineation on two HN cases, one with base-of-tongue (BOT) cancer and another with nasopharyngeal cancer (NPC), by first contouring from scratch and then by modifying the contours deformed by the CAT system. The gross target volumes were provided. Regions of interest for comparison included the clinical target volumes (CTVs) and normal organs. The volumetric and geometric variation of these regions of interest and the time spent on contouring were analyzed. RESULTS: We found that the variation in delineating CTVs from scratch among the physicians was significant, and that using the CAT system reduced volumetric variation and improved geometric consistency in both BOT and NPC cases. The average timesaving when using the CAT system was 26% to 29% for more experienced physicians and 38% to 47% for the less experienced ones. CONCLUSIONS: A computer-assisted target volume delineation approach, using a deformable image-registration method with template contours, was able to reduce the variation among physicians with different experiences in HN IMRT while saving contouring time.

The effect of dental artifacts, contrast media, and experience on interobserver contouring variations in head and neck anatomy.

OBJECTIVES: To investigate interobserver variability in the delineation of head-and-neck (H&N) anatomic structures on CT images, including the effects of image artifacts and observer experience. METHODS: Nine observers (7 radiation oncologists, 1 surgeon, and 1 physician assistant) with varying levels of H&N delineation experience independently contoured H&N gross tumor volumes and critical structures on radiation therapy treatment planning CT images alongside reference diagnostic CT images for 4 patients with oropharynx cancer. Image artifacts from dental fillings partially obstructed 3 images. Differences in the structure volumes, center-of-volume positions, and boundary positions (1 SD) were measured. In-house software created three-dimensional overlap distributions, including all observers. The effects of dental artifacts and observer experience on contouring precision were investigated, and the need for contrast media was assessed. RESULTS: In the absence of artifacts, all 9 participants achieved reasonable precision (1 SD < or =3 mm all boundaries). The structures obscured by dental image artifacts had larger variations when measured by the 3 metrics (1 SD = 8 mm cranial/caudal boundary). Experience improved the interobserver consistency of contouring for structures obscured by artifacts (1 SD = 2 mm cranial/caudal boundary). CONCLUSIONS: Interobserver contouring variability for anatomic H&N structures, specifically oropharyngeal gross tumor volumes and parotid glands, was acceptable in the absence of artifacts. Dental artifacts increased the contouring variability, but experienced participants achieved reasonable precision even with artifacts present. With a staging contrast CT image as a reference, delineation on a noncontrast treatment planning CT image can achieve acceptable precision.

Measuring head and neck cancer symptom burden: the development and validation of the M. D. Anderson symptom inventory, head and neck module.

BACKGROUND: The aim of this study was to develop and validate a symptom inventory for patients with head and neck cancer and to assess the occurrence and severity of symptoms, the overall symptom burden, and the interference the symptoms cause in daily life. METHODS: Items were generated from a comprehensive literature review, our prior work, and focus groups with head and neck cancer patients, symptom researchers, and a multidisciplinary group of head and neck cancer health care workers. We selected 11 provisional head and neck cancer-specific items for addition to the core M. D. Anderson Symptom Inventory (MDASI), and conducted a cross-sectional validation study among patients with head and neck cancer. RESULTS: Construct validity was established using principal axis factoring with direct oblimin rotation, and tests of concurrent and known-groups validity were conducted. Two items were dropped because of low severity scores and low frequency of complaint, leaving 9 final head and neck cancer-specific items. The coefficient alpha reliabilities were 0.88, 0.83, and 0.92 for the 13 core MDASI items, the 9 head and neck cancer-specific items, and the 6 interference items, respectively. The most prevalent severe symptoms were problems with mucus, mouth/throat sores, tasting food, difficulty with chewing or swallowing, dry mouth, pain, and fatigue. CONCLUSIONS: The M. D. Anderson Symptom Inventory-Head and Neck (MDASI-HN) is a reliable and valid instrument to measure head and neck cancer symptom burden, and the interference symptoms cause in the major aspects of a patient's daily life. A subset of specifically distressing symptoms was identified, many of which are not included in commonly used head and neck cancer quality of life instruments.

Importance of patient examination to clinical quality assurance in head and neck radiation oncology.

BACKGROUND: When quality assurance programs in clinical radiation oncology focus mainly on the technical aspects of treatment, they tend to underplay questions of therapeutic process and outcome. We determined the value of clinical peer review in radiation therapy for head and neck cancer that involved head and neck examination. METHODS: Data were collected prospectively on 134 consecutive patients with preliminary radiation therapy (RT) plans. Peer review was performed that included head and neck examination and imaging review to confirm target localization. RESULTS: Peer review led to changes in treatment plans for 66% of patients. Most changes were minor, but 11% of changes were major and thought to be of a magnitude that could potentially affect therapeutic outcome or normal tissue toxicity. Most changes involved target delineation based on physical findings CONCLUSIONS: Peer review of radiation target localization in RT plans led to changes that could potentially affect rates of cancer control or complication in about 10% of patients. We suggest that the accuracy of head and neck radiation oncology treatment plans might be increased by co-examination by another head and neck cancer specialist, typically a radiation oncologist or head and neck surgeon, to confirm RT target volumes.

Impact of changes to the American Joint Committee on Cancer T classification on outcome prediction in patients with oropharyngeal cancer.

BACKGROUND: The efficacy of the current 6th edition of the American Joint Committee on Cancer (AJCC) tumor staging criteria in improving outcome prediction for patients with oropharyngeal cancer was analyzed. METHODS: From the database of the Department of Radiation Oncology at the University of Texas M. D. Anderson Cancer Center the authors identified 875 patients irradiated at the study institution for oropharyngeal cancer between January 1975 and December 1998. The tumors were restaged based on the 6th edition of AJCC tumor staging criteria to reassess the original outcome predictions, specifically overall survival (OS) and local control (LC). RESULTS: Applying the new 6th edition staging system resulted in the following T classification distributions: T2, 301 tumors (34%); T3, 248 tumors (28%); T4a, 224 tumors (26%), and T4b, 102 tumors (12%). The 5-year and 10-year OS rates based on the new system were: T2, 65% and 45%; T3, 44% and 28%; T4a, 30% and 23%; and T4b, 26% and 12%, respectively. The 5-year and 10-year actuarial local LC rates based on the new system were: T2, 85% and 83%; T3, 73% and 71%; T4a, 61% and 58%; and T4b, 42% and 42%, respectively. Differences in OS and LC rates stratified by stage were found to be statistically significant both for the overall distribution of survival and pairwise comparisons of the 4 tumor stage groups. CONCLUSIONS: The modifications established in the 6th edition of the AJCC tumor staging system for oropharyngeal tumors appear to be useful to distinguish prognostic groups for both LC and OS based on tumor stage.

Determining optimal clinical target volume margins in head-and-neck cancer based on microscopic extracapsular extension of metastatic neck nodes.

PURPOSE: To determine the optimal clinical target volume margins around the gross nodal tumor volume in head-and-neck cancer by assessing microscopic tumor extension beyond cervical lymph node capsules. METHODS AND MATERIALS: Histologic sections of 96 dissected cervical lymph nodes with extracapsular extension (ECE) from 48 patients with head-and-neck squamous cell carcinoma were examined. The maximum linear distance from the external capsule border to the farthest extent of the tumor or tumoral reaction was measured. The trends of ECE as a function of the distance from the capsule and lymph node size were analyzed. RESULTS: The median diameter of all lymph nodes was 11.0 mm (range: 3.0-30.0 mm). The mean and median ECE extent was 2.2 mm and 1.6 mm, respectively (range: 0.4-9.0 mm). The ECE was <5 mm from the capsule in 96% of the nodes. As the distance from the capsule increased, the probability of tumor extension declined. No significant difference between the extent of ECE and lymph node size was observed. CONCLUSION: For N1 nodes that are at high risk for ECE but not grossly infiltrating musculature, 1 cm clinical target volume margins around the nodal gross tumor volume are recommended to cover microscopic nodal extension in head-and-neck cancer.

Parathyroid carcinoma: a 22-year experience.

PURPOSE: Because parathyroid carcinoma is rare, clear consensus is not available regarding the optimal management of patients with this condition. Treatment strategies generally derive from clinical and anecdotal experiences. We report our experience with this entity. METHODS: We included all patients with parathyroid carcinoma seen at The University of Texas M. D. Anderson Cancer Center since January 1, 1980. The medical records and pathology specimens were reviewed and verified in all cases. RESULTS: Since 1980, 27 patients (16 men and 11 women) registered at M. D. Anderson Cancer Center with parathyroid carcinoma and a minimum follow-up of 2 years. The age at initial diagnosis (mean +/- SD) was 46.7 +/- 15.3 years. All patients were seen with hypercalcemia (mean calcium, 13.4 +/- 1.5 mg/dL). Eighteen patients had locally invasive disease, eight had localized disease, and one had distant metastasis. Parathyroid cancer was treated with complete surgical excision with curative intent in 18 patients. In the other nine patients, who had clinical and/or radiographic evidence of soft tissue extension, the tumor was treated by comprehensive "en bloc" soft tissue resection. Of six patients who received adjuvant radiotherapy after initial surgery, only one had a local relapse. In contrast, of 20 patients who did not receive adjuvant radiotherapy, 10 had a local relapse, excluding the one patient who had distant metastases. The 5-year survival was 85%, and the 10-year survival was 77%. Five patients died of parathyroid carcinoma; all deaths were hypercalcemia related. CONCLUSIONS: Parathyroid carcinoma can be an indolent disease with morbidity and mortality related to hypercalcemia. Adjuvant radiotherapy may improve local control and limit the occurrence of local relapse. A comprehensive multidisciplinary approach with surgery, radiation therapy, and medical treatment for hypercalcemia is needed to optimize patient outcome.

Is concurrent chemoradiation the treatment of choice for all patients with Stage III or IV head and neck carcinoma?

BACKGROUND: Many patients with small primary tumors of the oropharynx have AJCC Stage III/IV disease on the basis of lymphadenopathy. In the current retrospective study, the authors hypothesized that these patients have high rates of locoregional control when treated with radiotherapy, either alone or combined with neck surgery, and may not require concurrent chemotherapy. METHODS: Two hundred ninety-nine patients met staging and inclusion criteria. Stage distribution was as follows: T1, 99 patients (33%); T2, 182 patients (61%); Tx, 18 patients (6%); N1, 74 patients (25%); N2, 170 patients (57%); N3, 39 patients (13%); and Nx, 16 patients (5%). Primary tumor resection or tonsillectomy had been performed in 36 patients (12%) and excisional lymph node biopsy or formal neck dissection in 192 patients (64%). Thirty-three additional patients (10%) received chemotherapy and were analyzed separately. RESULTS: The median follow-up was 82 months (range, 8-299 months). The actuarial 5-year rates of locoregional failure, distant metastases, and overall survival were 15%, 19%, and 64%, respectively. T status was associated with the 5-year rate of locoregional control: 95% for patients with T1-/Tx disease, compared with 79% for patients with T2 disease (P < 0.01). The 5-year rate of distant metastases for patients with N1/2a disease was 11%, compared with 28% for patients with N2b/N2c/N3 disease (P < 0.001). CONCLUSIONS: Patients with early-T status oropharyngeal carcinoma, which is considered advanced due to the presence of lymphadenopathy, have high rates of locoregional control when treated with radiotherapy without or with neck surgery. Local treatment intensification by the addition of concurrent chemotherapy to radiotherapy would not significantly benefit most of these patients.