Head and Neck Cancer

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MO_23_2464 - Medulla Dose is Positively Associated with Sensation of Thirst & Midbrain Dose is Inversely Associated with Pain: Prospectively-Collected Patient-Reported Toxicities and Brainstem Dose in Head and Neck Cancer Radiation Therapy

Monday, October 22
10:45 AM - 12:15 PM
Location: Innovation Hub, Exhibit Hall 3

Medulla Dose is Positively Associated with Sensation of Thirst & Midbrain Dose is Inversely Associated with Pain: Prospectively-Collected Patient-Reported Toxicities and Brainstem Dose in Head and Neck Cancer Radiation Therapy
M. J. Ferris1, J. Switchenko2, C. Xiao3, M. W. McDonald4, B. R. Eaton1, K. A. Higgins1, R. H. Press1, S. Tian5, C. Steuer6, H. M. Baddour7, A. H. Miller8, D. W. Bruner3, and J. J. Beitler1; 1Department of Radiation Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, 2Department of Biostatistics & Bioinformatics, Rollins School of Public Health, and Winship Cancer Institute at Emory University, Atlanta, GA, 3Nell Hodgson Woodruff School of Nursing, and Winship Cancer Institute at Emory University, Atlanta, GA, 4Department of Radiation Oncology and Winship Cancer Institute, Emory University, Atlanta, GA, 5Department of Radiation Oncology, and Winship Cancer Institute at Emory University, Atlanta, GA, 6Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, 7Department of Otolaryngology―Head and Neck Surgery, and Winship Cancer Institute at Emory University, Atlanta, GA, 8Department of Psychiatry and Behavioral Sciences, and Winship Cancer Institute at Emory University, Atlanta, GA

Purpose/Objective(s): Toxicity control—best assessed via patient reported outcome (PRO) metrics—is essential in the treatment of head and neck cancer (HNC) with radiation therapy (RT). The brain can modulate most physiologic systems, and dose to key areas during HNC RT may alter patient physiology or perceptions.

Materials/Methods: Patients enrolled in a prospective institutional protocol answered NCI PRO-CTCAETM questionnaires at pre-RT, 6th week of RT and 1-month post-RT time points. Brain substructures—medulla, pons, midbrain, pituitary, cerebellum, and posterior fossa—were retrospectively contoured for all patients. Substructure dosimetry variables (Dmean, Dmax, and D2%—maximum dose received to 2% of volume) were extracted and analyzed for associations with twelve PRO toxicities. Pre-RT values were controlled for in all cases. Multivariable (MV) analyses were performed, and included the additional covariates: T-stage, N-stage, post-operative RT vs. RT for intact disease, contralateral parotid mean dose, and oral cavity mean dose.

Results: From March 2013 to January 2017, 124 patients (96 males, 28 females) were available. Median age 59 (38 – 89); 70.2% received RT for intact disease, 29.8% received post-operative RT; 86.3% received concurrent chemotherapy; primary sites: oropharynx (54.8%), larynx (14.5%), oral cavity (12.9%), hypopharynx (8.1%), other (9.7%). Table 1 displays the statistically significant results from the separate MV models performed (dose grouped by quartiles)—it shows a positive association between medulla dosimetry and Grade ≥3 sensation of thirst, and an inverse association between midbrain dosimetry and Grade ≥2 pain. Besides medulla Dmax/D2%, no additional covariates were associated with Grade ≥3 sensation of thirst. Besides midbrain D2%, no other covariates were associated with Grade ≥2 pain except for oral cavity mean dose (OR 1.05; 95% CI 1.01 – 1.08; P = 0.012). No other relationships between substructure dosimetry and PROs were significant.

Conclusion: Brainstem dose may have consequences that were previously unappreciated. The medulla houses the solitary nucleus—a critical component of taste perception—offering a mechanism explaining the association found between dose and sensation of thirst. The midbrain houses the periaqueductal gray—a primary control center for descending pain modulation and the target of stimulating implants for chronic pain patients—offering a mechanism behind this analgesic effect of midbrain dose. Table 1.
Variable Quartile Range (Gy) Odds Ratio (95% CI) P-value
Grade ≥3 sensation of thirst
Medulla Dmax >37.5 – ≤62.7 5.67 (1.37 – 23.45) 0.017
>33.2 – ≤37.5 6.52 (1.58 – 26.84) 0.009
>27.6 – ≤33.2 4.64 (1.09 – 19.67) 0.037
>0.2 – ≤27.6
Medulla D2% >35.1 – ≤55.9 3.51 (0.95 – 12.99) 0.060
>29.6 – ≤35.1 6.12 (1.68 – 22.22) 0.006
>24.0 – ≤29.6 2.36 (0.60 – 9.18) 0.217
>0.3 – ≤24.0
Grade ≥2 pain
Midbrain D2% >3.2 – ≤42.8 0.14 (0.03-0.54) 0.005
>2.6 – ≤3.2 0.48 (0.13-1.78) 0.272
>1.9 – ≤2.6 0.47 (0.12-1.81) 0.273
>0.7 – ≤1.9

Author Disclosure: M.J. Ferris: None. J. Switchenko: None. C. Xiao: None. M.W. McDonald: medical director; Emory Proton Therapy Center. B.R. Eaton: None. K.A. Higgins: Consultant; Astra Zeneca. C. Steuer: None. H.M. Baddour: None.

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MO_23_2464 - Medulla Dose is Positively Associated with Sensation of Thirst & Midbrain Dose is Inversely Associated with Pain: Prospectively-Collected Patient-Reported Toxicities and Brainstem Dose in Head and Neck Cancer Radiation Therapy



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