Prospective assessment of sparing the parotid ducts via MRI sialography for reducing patient reported xerostomia.

PURPOSE: To assess the impact of prospectively sparing the parotid ducts via MRI sialography on patient reported xerostomia for those receiving definitive radiotherapy (RT) for oropharyngeal squamous cell carcinoma. METHODS AND MATERIALS: Thirty-eight patients with oropharynx cancer to be treated with definitive RT underwent pre-treatment MRI sialograms to localize their parotid ducts. The parotid ducts were maximally spared during treatment planning. Patients reported symptoms (PRO-CTCAE and QLQ-H&N35) were collected at 6 and 12 months post-RT and compared to a historical cohort who underwent conventional parotid gland mean dose sparing. Regression models were generated using parotid and submandibular gland doses with and without incorporating the dose to the parotid ducts to determine the impact of parotid duct dose on patient reported xerostomia. RESULTS: At 6 months post-RT, 12/26 (46%) patients reported ≥moderate xerostomia when undergoing parotid ductal sparing compared to 43/61 (70%) in the historical cohort (p = 0.03). At 12 months post-RT, 8/22 (36%) patients reported ≥moderate xerostomia when undergoing parotid ductal sparing compared to 34/68(50%) in the historical cohort (p = 0.08). Using nested logistic regression models, the mean parotid duct dose was found to significantly relate to patient reported xerostomia severity at 6 months post-RT (p = 0.04) and trended towards statistical significance at 12 months post-RT (p = 0.09). At both 6 and 12 months post-RT, the addition of mean parotid duct dose significantly improved model fit (p < 0.05). CONCLUSIONS: MRI sialography guided parotid duct sparing appears to reduce the rates of patient-reported xerostomia. Further, logistic regression analysis found parotid duct dose to be significantly associated with patient reported xerostomia. A significant improvement in model fit was observed when adding mean parotid duct dose compared to models that only contain mean parotid gland dose and mean contralateral submandibular gland dose.

Prospective Assessment of Patient-Reported Dry Eye Syndrome After Whole Brain Radiation.

PURPOSE: Dry eye is not typically considered a toxicity of whole brain radiation therapy (WBRT). We analyzed dry eye syndrome as part of a prospective study of patient-reported outcomes after WBRT. METHODS AND MATERIALS: Patients receiving WBRT to 25 to 40 Gy were enrolled on a study with dry mouth as the primary endpoint and dry eye syndrome as a secondary endpoint. Patients received 3-dimensional WBRT using opposed lateral fields. Per standard practice, lacrimal glands were not prospectively delineated. Patients completed the Subjective Evaluation of Symptom of Dryness (SESoD, scored 0-4, with higher scores representing worse dry eye symptoms) at baseline, immediately after WBRT (EndRT), and at 1 month (1M), 3 months, and 6 months. Patients with baseline SESoD ≥3 (moderate dry eye) were excluded. The endpoints analyzed were ≥1-point and ≥2-point increase in SESoD score at 1M. Lacrimal glands were retrospectively delineated with fused magnetic resonance imaging scans. RESULTS: One hundred patients were enrolled, 70 were eligible for analysis, and 54 were evaluable at 1M. Median bilateral lacrimal V20Gy was 79%. At 1M, 17 patients (32%) had a ≥1-point increase in SESoD score, and 13 (24%) a ≥2-point increase. Lacrimal doses appeared to be associated with an increase in SESoD score of both ≥1 point (V10Gy: P = .042, odds ratio [OR] 1.09/%; V20Gy: P = .071, OR 1.03/%) and ≥2 points (V10Gy: P = .038, OR 1.15/%; V20Gy: P = .063, OR 1.04/%). The proportion with increase in dry eye symptoms at 1M for lacrimal V20Gy ≥79% versus <79% was 46% versus 15%, respectively, for ≥1 point SESoD increase (P = .02) and 36% versus 12%, respectively, for ≥2 point SESoD increase (P = .056). CONCLUSIONS: Dry eye appears to be a relatively common, dose/volume-dependent acute toxicity of WBRT. Minimization of lacrimal gland dose may reduce this toxicity, and patients should be counseled regarding the existence of this potential side effect and treatments for dry eye.

Assessment of Risk of Xerostomia After Whole-Brain Radiation Therapy and Association With Parotid Dose.

Importance: Whole-brain radiation therapy (WBRT) delivers a substantial radiation dose to the parotid glands, but the parotid glands are not delineated for avoidance and xerostomia has never been reported as an adverse effect. Minimizing the toxic effects in patients receiving palliative treatments, such as WBRT, is crucial. Objective: To assess whether xerostomia is a toxic effect of WBRT. Design, Setting, and Participants: This observational cohort study enrolled patients from November 2, 2015, to March 20, 2018, at 1 academic center (University of North Carolina Hospitals) and 2 affiliated community hospitals (High Point Regional Hospital and University of North Carolina Rex Hospital). Adult patients (n = 100) receiving WBRT for the treatment or prophylaxis of brain metastases were enrolled. Patients who had substantial baseline xerostomia or did not complete WBRT or at least 1 postbaseline questionnaire were prospectively excluded from analysis and follow-up. Patients received 3-dimensional WBRT using opposed lateral fields covering the skull and the C1 or C2 vertebra. Per standard practice, the parotid glands were not prospectively delineated. Main Outcomes and Measures: Patients completed the University of Michigan Xerostomia Questionnaire and a 4-point bother score at baseline, immediately after WBRT, at 1 month, at 3 months, and at 6 months. The primary end point was the 1-month xerostomia score, with a hypothesized worsening score of 10 points from baseline. Results: Of the 100 patients enrolled, 73 (73%) were eligible for analysis and 55 (55%) were evaluable at 1 month. The 73 patients included 43 women (59%) and 30 men (41%) with a median (range) age of 61 (23-88) years. The median volume of parotid receiving at least 20 Gy (V20Gy) was 47%. The mean xerostomia score was 7 points at baseline and was statistically significantly higher at each assessment period, including 21 points immediately after WBRT (95% CI, 16-26; P < .001), 23 points (95% CI, 16-30; P < .001) at 1 month, 21 points (95% CI, 13-28; P < .001) at 3 months, and 14 points (95% CI, 7-21; P = .03) at 6 months. At 1 month, the xerostomia score increased by 20 points or more in 19 patients (35%). The xerostomia score at 1 month was associated with parotid dose as a continuous variable and was 35 points in patients with parotid V20Gy of 47% or greater, compared with only 9 points in patients with parotid V20Gy less than 47% (P < .001). The proportion of patients who self-reported to be bothered quite a bit or bothered very much by xerostomia at 1 month was 50% in those with parotid V20Gy of 47% or greater, compared with only 4% in those with parotid V20Gy less than 47% (P < .001). At 3 months, this difference was 50% vs 0% (P = .001). Xerostomia was not associated with medication use. Conclusions and Relevance: Clinically significant xerostomia occurred by the end of WBRT, appeared to be persistent, and appeared to be associated with parotid dose. The findings from this study suggest that the parotid glands should be delineated for avoidance to minimize these toxic effects in patients who undergo WBRT and often do not survive long enough for salivary recovery.

Assessment of PlanIQ Feasibility DVH for head and neck treatment planning.

INTRODUCTION: Designing a radiation plan that optimally delivers both target coverage and normal tissue sparing is challenging. There are limited tools to determine what is dosimetrically achievable and frequently the experience of the planner/physician is relied upon to make these determinations. PlanIQ software provides a tool that uses target and organ at risk (OAR) geometry to indicate the difficulty of achieving different points for organ dose-volume histograms (DVH). We hypothesized that PlanIQ Feasibility DVH may aid planners in reducing dose to OARs. METHODS AND MATERIALS: Clinically delivered head and neck treatments (clinical plan) were re-planned (re-plan) putting high emphasis on maximally sparing the contralateral parotid gland, contralateral submandibular gland, and larynx while maintaining routine clinical dosimetric objectives. The planner was blinded to the results of the clinically delivered plan as well as the Feasibility DVHs from PlanIQ. The re-plan treatments were designed using 3-arc VMAT in Raystation (RaySearch Laboratories, Sweden). The planner was then given the results from the PlanIQ Feasibility DVH analysis and developed an additional plan incorporating this information using 4-arc VMAT (IQ plan). The DVHs across the three treatment plans were compared with what was deemed "impossible" by PlanIQ's Feasibility DVH (Impossible DVH). The impossible DVH (red) is defined as the DVH generated using the minimal dose that any voxel outside the targets must receive given 100% target coverage. RESULTS: The re-plans performed blinded to PlanIQ Feasibilty DVH achieved superior sparing of aforementioned OARs compared to the clinically delivered plans and resulted in discrepancies from the impossible DVHs by an average of 200-700 cGy. Using the PlanIQ Feasibility DVH led to additionalOAR sparing compared to both the re-plans and clinical plans and reduced the discrepancies from the impossible DVHs to an average of approximately 100 cGy. The dose reduction from clinical to re-plan and re-plan to IQ plan were significantly different even when taking into account multiple hypothesis testing for both the contralateral parotid and the larynx (P < 0.004 for all comparisons). No significant differences were observed between the three plans for the contralateral parotid when considering multiple hypothesis testing. CONCLUSIONS: Clinical treatment plans and blinded re-plans were found to suboptimally spare OARs. PlanIQ could aid planners in generating treatment plans that push the limits of OAR sparing while maintaining routine clinical target coverage goals.

Reducing Unplanned Admissions: Focusing on Hospital Admissions and Emergency Department Visits for Patients With Head and Neck Cancer During Radiation Therapy
.

BACKGROUND: Head and neck cancer (HNC) treatments cause severe toxicities, leading to high rates of emergency department (ED) visits and unplanned hospital admissions (UHAs). 
. OBJECTIVES: The study aimed to evaluate a quality improvement project to reduce ED visits and UHAs.
. METHODS: A weekly nurse/nurse practitioner-led symptom management clinic was created for patients with HNC receiving radiation therapy deemed at high risk for an ED visit or UHA. Primary quality metrics were rate of visits or unplanned admissions. Time-to-event actuarial analysis and log-rank tests (two-tailed) were performed to compare observed to historic rates. 
. FINDINGS: Rates of ED visits and UHAs were 11% and 16%, respectively. Having more symptom management visits marginally correlated with reduction in UHA. The authors estimate six ED visits and four UHAs were prevented, which is a $176,848 cost reduction.

Costs of care in a matched pair comparison of intensity-modulated radiation therapy (IMRT) versus conventional radiation therapy (CRT) for the treatment of head and neck cancer.

OBJECTIVES: Intensity-modulated radiation therapy (IMRT) has been rapidly adopted for the treatment of head and neck cancer. Limited comparative effectiveness data suggest that IMRT reduces the incidence of xerostomia and improves quality of life. We assess the cost of IMRT versus the older conventional radiation therapy (CRT) relative to other potential drivers of cost in patients with head and neck cancer. METHODS: We compared patients treated with definitive radiation with or without chemotherapy for squamous cell carcinoma of the head and neck treated between 2000 and 2009. IMRT-treated patients were matched to CRT-treated patients by site, stage, and smoking status. Itemized billing charges were obtained for each patient and used to estimate cost using the Medicare fee schedule. Multivariate analysis was used to assess the influence of demographic, clinical, and treatment variables on total, pretreatment, during treatment, and follow-up costs. RESULTS: Models indicate that compared with CRT, IMRT was associated with, on average, a $5881 increase in total costs (P=0.043), a $1700 decrease in pretreatment costs (P=0.014), a $4768 increase in costs during treatment (P=0.004), and no significant difference in follow-up costs. Positron emission tomography scans, cancer recurrence, and comorbidity were also associated with higher total costs in this sample. CONCLUSIONS: Use of IMRT relative to CRT was strongly correlated with higher total costs, but disease control, patient comorbidity, and use of positron emission tomography also had significant effects on overall costs. Cost-effectiveness models should be developed to assess whether the potential benefits of IMRT are worth the associated investment.

Two-year and lifetime cost-effectiveness of intensity modulated radiation therapy versus 3-dimensional conformal radiation therapy for head-and-neck cancer.

PURPOSE: To assess the cost-effectiveness of intensity modulated radiation therapy (IMRT) versus 3-dimensional conformal radiation therapy (3D-CRT) in the treatment of head-and neck-cancer (HNC). METHODS AND MATERIALS: We used a Markov model to simulate radiation therapy-induced xerostomia and dysphagia in a hypothetical cohort of 65-year-old HNC patients. Model input parameters were derived from PARSPORT (CRUK/03/005) patient-level trial data and quality-of-life and Medicare cost data from published literature. We calculated average incremental cost-effectiveness ratios (ICERs) from the US health care perspective as cost per quality-adjusted life-year (QALY) gained and compared our ICERs with current cost-effectiveness standards whereby treatment comparators less than $50,000 per QALY gained are considered cost-effective. RESULTS: In the first 2 years after initial treatment, IMRT is not cost-effective compared with 3D-CRT, given an average ICER of $101,100 per QALY gained. However, over 15 years (remaining lifetime on the basis of average life expectancy of a 65-year-old), IMRT is more cost-effective at $34,523 per QALY gained. CONCLUSION: Although HNC patients receiving IMRT will likely experience reduced xerostomia and dysphagia symptoms, the small quality-of-life benefit associated with IMRT is not cost-effective in the short term but may be cost-effective over a patient's lifetime, assuming benefits persist over time and patients are healthy and likely to live for a sustained period. Additional data quantifying the long-term benefits of IMRT, however, are needed.

Patterns of care in older patients with squamous cell carcinoma of the head and neck: a surveillance, epidemiology, and end results-medicare analysis.

BACKGROUND: There is growing evidence in the literature that older patients may not benefit from more intensive therapy for head and neck squamous cell carcinoma (HNSCC). A growing number of patients with HNSCC are age 65 years or older; however, much of the evidence base informing treatment decisions is based on substantially younger and healthier clinical trial populations. The purpose of this study was to assess the patterns of care of older HNSCC patients to better understand how age is associated with treatment decisions. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database (1992­2007), we identified patients with non-metastatic HNSCC (n = 10,867) and categorized them by treatment: surgery vs. non-surgery and chemoradiotherapy (CRT) vs. radiotherapy (RT). Multivariate logistic regression models were used to identify variables associated with the receipt of surgery and CRT. RESULTS: Increasing age was associated with decreased odds of receiving CRT (OR = 0.94; 95% CI 0.93­0.94) but not surgery (OR 1.00; 95% CI 0.99­1.00). Co-morbidity and race were not associated with receipt of either surgery or CRT. Utilization of CRT increased while surgery decreased between 1992 and 2007. CONCLUSION: Age may influence the receipt of CRT for older HNSCC patients. There has been an increasing trend in the receipt of CRT and a decrease in primary surgery.