Radiation-associated Dysphagia Research Articles

Radiation Therapy Dose-Volume Correlates Predict Videofluoroscopy-Detected Dysphagia Per DIGEST after IMRT for Oropharyngeal Carcinoma: Results of a Prospective Registry

Our primary aim was to prospectively validate retrospectively studied dosimetric parameters predictive of radiation-associated dysphagia (RAD) after intensity modulated radiation therapy (IMRT) for oropharyngeal cancer (OPC). The secondary aim was to validate grade ≥2 dichotomization of a published videofluoroscopic dysphagia grade (Dynamic Imaging Grade for Swallowing Toxicity, DIGEST) as a radiation dose-sensitive cutoff for RAD. Ninety-seven patients with stage I-IV OPC underwent videofluoroscopy pre- and 3-6 months after IMRT per an IRB-approved prospective registry protocol. Dysphagia severity was graded per DIGEST criteria (dichotomized grade≥2 as moderate/severe RAD). Multivariate regression analysis identified clinical and dosimetric predictors of RAD. Dose-volume histogram (DVH) of superior/ middle/inferior pharyngeal constrictors (S/M/IPC), intrinsic tongue muscle (ITM), geniohyoid muscle (GHM), genioglossus muscle (GGM), mylohyoid muscle (MHM), anterior digastric muscle (ADM), and glottic, supraglottic areas were calculated. Recursive partitioning analysis (RPA) and Bayesian Information Criteria (BIC) were used to identify dose-volume effects associated with moderate/severe RAD. The median age was 61 (range: 35–86) years and 47% were current/former smokers. The majority of tumors (47%) originated from the base of the tongue; 27% and 48% of the patients presented with advanced T (i.e., T3-4) and N2 disease, respectively. HPV/p16 status was positive in 95% of tumors. Concurrent chemotherapy (CRT) was delivered in 23%. Median RT dose was 69.96 (range: 50-70) Gy. At 3-6 months after IMRT, 70% had MBS-evident RAD (DIGEST grade ≥1) and 31% had moderate/severe dysphagia (i.e. DIGEST grade ≥2). Intensified treatment modalities (induction+CRT), advanced T stage, in addition to higher RT mean dose of GHM and GGM (p=0.004 and 0.0089, respectively) were significantly associated with moderate/severe RAD in multivariate analysis. RPA identified GHM V61 ≥ 18.57% (LogWorth 7.3, p<0.0001), SPC V55 ≥ 97.46% (LogWorth 3.8, p=0.0001) and supraglottic V23 ≥92.54% (LogWorth 2.8, p=0.001) as dose-volume thresholds for moderate/severe RAD (AUC 0.9 and 0.7 across training and validation sets, respectively). V61 ≥ 18.57% of GHM had the optimal model performance for prediction of DIGEST grade ≥2 in the subsequent multivariate analysis. The findings from this prospective longitudinal study validate prior observations that dose to submental musculature predicts increased burden of dysphagia after oropharyngeal IMRT. Findings also support dichotomization of DIGEST grade ≥2 as a dose-dependent split for use in endpoint reporting or predictive dose-response analysis of videofluoroscopy results.

A prospective longitudinal assessment of MRI signal intensity kinetics of non-target muscles in patients with advanced stage oropharyngeal cancer in relationship to radiotherapy dose and post-treatment radiation-associated dysphagia: Preliminary findings from a randomized trial

PurposeTo assess quantitative signal intensity (SI) kinetics obtained from serial MRI of swallowing muscles as a potential imaging biomarker of radiation-induced dysphagia in oropharyngeal cancer (OPC) patients receiving radiotherapy (RT). MethodsPatients were enrolled under an IRB approved Phase II/III randomized trial. Patients underwent serial MRIs at pre-, mid-, and post-RT. Normalized T1, T1+ contrast (T1 + C), and T2 SI for swallowing muscle volumes-of-interest (VOIs) were collected and delta SI changes (Δ) were calculated. Mid- and post-RT SI relative to baseline were assessed and correlations between radiation dose and percent change in SI were calculated. Independent samples’ t-tests were used to compare the percent change of SI between patients divided into two groups based on dysphagia status post-RT. ResultsForty-six patients with stage III/IV HPV+ OPC were included in this study. Relative to baseline, mean T2 and T1 + C SIs for middle pharyngeal constrictor were both significantly higher at mid- and post-RT (p < 0.004 for all). Superior pharyngeal constrictor also showed a significant increase in T1 + C SI at mid-RT (p = 0.0004). Additional muscle VOIs showed significant changes post-RT, but not earlier at mid-RT. Both mid- and post-RT doses were significantly correlated with the percent change of normalized T2 and T1 + C SI for examined muscle VOIs (p < 0.002). Mean percent changes of normalized T2 SI at mid-RT relative to baseline for all muscle VOIs were significantly higher in patients who developed grade ≥2 dysphagia relative to patients with no/mild dysphasia (mean Δ%: 8.2% vs 1.9%; respectively, p = 0.002). However, at post-RT, these changes were only significant in T1 SI (11.2% vs −1.3%; p < 0.0001). ConclusionSignal intensity kinetics of radiation injury can be broadly correlated with the functional muscular defect. Serial MRI during the course of RT may provide an opportunity to quantitatively track muscular pathology for subclinical detection of patients at high risk to develop dysphagia.

Radiotherapy dose–volume parameters predict videofluoroscopy-detected dysphagia per DIGEST after IMRT for oropharyngeal cancer: Results of a prospective registry

PurposeOur primary aim was to prospectively validate retrospective dose–response models of chronic radiation-associated dysphagia (RAD) after intensity modulated radiotherapy (IMRT) for oropharyngeal cancer (OPC). The secondary aim was to validate a grade ≥2 cut-point of the published videofluoroscopic dysphagia severity (Dynamic Imaging Grade for Swallowing Toxicity, DIGEST) as radiation dose-dependent. Material and methodsNinety-seven patients enrolled on an IRB-approved prospective registry protocol with stage I–IV OPC underwent pre- and 3–6 month post-RT videofluoroscopy. Dose–volume histograms (DVH) for swallowing regions of interest (ROI) were calculated. Dysphagia severity was graded per DIGEST criteria (dichotomized with grade ≥2 as moderate/severe RAD). Recursive partitioning analysis (RPA) and Bayesian Information Criteria (BIC) were used to identify dose–volume effects associated with moderate/severe RAD. Results31% developed moderate/severe RAD (i.e. DIGEST grade ≥2) at 3–6 months after RT. RPA found DVH-derived dosimetric parameters of geniohyoid/mylohyoid (GHM), superior pharyngeal constrictor (SPC), and supraglottic region were associated with DIGEST grade ≥2 RAD. V61 ≥ 18.57% of GHM demonstrated optimal model performance for prediction of DIGEST grade ≥2. ConclusionThe findings from this prospective longitudinal registry validate prior observations that dose to submental musculature predicts for increased burden of dysphagia after oropharyngeal IMRT. Findings also support dichotomization of DIGEST grade ≥2 as a dose-dependent split for use as an endpoint in trials or predictive dose–response analysis of videofluoroscopy results.

(OA32) Chronic Radiation-Associated Dysphagia in Oropharyngeal Cancer Survivors: Towards Age-Adjusted Dose Constraints for Deglutitive Muscles

Chronic radiation-associated dysphagia (RAD) is a dreaded complication following head and neck radiotherapy. Different factors likely contribute to the development of late RAD. We hypothesize that age may be a significant factor predisposing patients to develop long term swallow dysfunction. We sought to model chronic RAD in patients treated with IMRT for oropharyngeal cancer as a function of age at time of treatment and dose to non-target swallowing muscle regions of interest (ROIs). We examined a group of 300 patients with T1-T4N0-3M0 oropharyngeal cancer patients who received definitive IMRT and concurrent chemotherapy at the University of Texas MD Anderson Cancer Center between 2002 - 2013. Chronic RAD was defined as any of the following ≥ 12 months post-IMRT: videoflouroscopy/endoscopy detected aspiration or stricture, gastrostomy tube, and/or aspiration pneumonia. DICOM-RT plan data were autosegmented using a validated region-of-interest (ROI) library and included inferior, middle and superior constrictors (IPC, MPC, and SPC), anterior and posterior digastrics (ADM, PDM), mylo/geniohyoid complex (MGM), intrinsic tongue muscles (ITM), and gengioglossus (GGM). Age was binned by decade of life, <50, 50-59, 60-69, and >=70 years of age. The probability of chronic RAD as a function of mean dose (to the above ROIs), stratified by age, was estimated by using logistic probability models and subsequent unsupervised nonlinear curve. Of 300 patients, 34 patients developed chronic RAD (11%). Age as a continuous and discrete variable was a significant correlate of chronic RAD, both independently and in concert with continuous dose for all muscle groups examined. Substantively distinct muscle-specific dose-response profiles were observed as a function of age (e.g. a patient in their 50s who received 60 Gy to the SPC had an observed 5% chronic-RAD rate, while a 70-year-old cohort (at the same dose level) exhibited a 20% rate.) Serial muscle-specific dose-response analysis demonstrated the effect to be stable across all observed muscle ROIs, with a FDR-corrected p<0.05 for all dose/muscle/age models, suggesting that an inclusion of dose as a covariate improves modeling of chronic RAD. Age at time of treatment appears to moderate dose-response probability of chronic RAD after chemo-IMRT for OPSCC. Our data demonstrate aging muscles show lower dose thresholds toward the development of potentially meaningful clinically apparent late RAD. Further investigation into age-specific dose constraints and age-adjusted dysphagia prophylaxis models appears warranted; however, our data suggest that uniform monolithic dose constraints may fail to accurately prognosticate or preclude clinical toxicity in aged populations.

Outcomes of patients diagnosed with carcinoma metastatic to the neck from an unknown primary source and treated with intensity-modulated radiation therapy.

There are few published studies to guide the treatment of carcinoma metastatic to the neck from an unknown primary (CUP). In this regard, the objective of the current study was to share the authors' current experience treating patients with CUP using intensity-modulated radiation therapy (IMRT), which principally targeted both sides of the neck, the nasopharynx, and the oropharynx. This was a retrospective study in which an institutional database search was conducted to identify patients with CUP who received IMRT. Data analysis included frequency tabulation, survival analysis, and multivariable analysis. Two-hundred sixty patients met inclusion criteria. The most common lymph node category was N2b (54%). IMRT volumes included the entire pharyngolaryngeal mucosa in 78 patients, the nasopharynx and oropharynx in 167 patients, and treatment limited to the involved neck in 11 patients. Eighty-four patients underwent neck dissections. The 5-year overall survival, regional control, and distant metastases-free survival rates were 84%, 91%, and 94%, respectively. Over 40% of patients had gastrostomy tubes during therapy, and 7% patients were diagnosed with chronic radiation-associated dysphagia. Higher lymph node burden was associated with worse disease-related outcomes, and in subgroup analysis, patients with human papillomavirus-associated disease had better outcomes. No therapeutic modality was statistically associated with either disease-related outcomes or toxicity. Comprehensive IMRT with treatment to both sides of the neck and to the oropharyngeal and nasopharyngeal mucosa results in high rates of disease control and survival. The investigators were unable to demonstrate that treatment intensification with chemotherapy or surgery added benefit or excessive toxicity. Cancer 2018;124:1415-27. © 2018 American Cancer Society.

EP-1037: Chronic radiation-associated dysphagia (RAD) after curative reirradiation in head and neck cancer

EP-1037: Chronic radiation-associated dysphagia (RAD) after curative reirradiation in head and neck cancer

PO-144: Chronic radiation-associated dysphagia after curative reirradiation. Does age affect?

PO-144: Chronic radiation-associated dysphagia after curative reirradiation. Does age affect?

Chronic radiation-associated dysphagia (RAD) after curative reirradiation or chemo-reirradiation in head and neck cancer

Chronic radiation-associated dysphagia (RAD) after curative reirradiation or chemo-reirradiation in head and neck cancer

Beyond mean pharyngeal constrictor dose for beam path toxicity in non-target swallowing muscles: Dose–volume correlates of chronic radiation-associated dysphagia (RAD) after oropharyngeal intensity modulated radiotherapy

Purpose/objective(s)We sought to identify swallowing muscle dose–response thresholds associated with chronic radiation-associated dysphagia (RAD) after IMRT for oropharyngeal cancer. Materials/methodsT1–4 N0–3 M0 oropharyngeal cancer patients who received definitive IMRT and systemic therapy were examined. Chronic RAD was coded as any of the following ⩾12months post-IMRT: videofluoroscopy/endoscopy detected aspiration or stricture, gastrostomy tube and/or aspiration pneumonia. DICOM-RT plan data were autosegmented using a custom region-of-interest (ROI) library and included inferior, middle and superior constrictors (IPC, MPC, and SPC), medial and lateral pterygoids (MPM, LPM), anterior and posterior digastrics (ADM, PDM), intrinsic tongue muscles (ITM), mylo/geniohyoid complex (MHM), genioglossus (GGM), masseter (MM), buccinator (BM), palatoglossus (PGM), and cricopharyngeus (CPM), with ROI dose–volume histograms (DVHs) calculated. Recursive partitioning analysis (RPA) was used to identify dose–volume effects associated with chronic-RAD, for use in a multivariate (MV) model. ResultsOf 300 patients, 34 (11%) had chronic-RAD. RPA showed DVH-derived MHM V69 (i.e. the volume receiving⩾69Gy), GGM V35, ADM V60, MPC V49, and SPC V70 were associated with chronic-RAD. A model including age in addition to MHM V69 as continuous variables was optimal among tested MV models (AUC 0.835). ConclusionIn addition to SPCs, dose to MHM should be monitored and constrained, especially in older patients (>62-years), when feasible.

Impact of selective neck dissection on chronic dysphagia after chemo-intensity-modulated radiotherapy for oropharyngeal carcinoma.

Conflicting results are reported regarding the impact of neck dissection on radiation-associated dysphagia. The purpose of this study was to reexamine this question specific to oropharyngeal intensity-modulated radiotherapy (IMRT). Three hundred forty-nine patients with oropharyngeal cancer treated with bilateral IMRT with systemic therapy (induction and/or concurrent) were reviewed. Chronic dysphagia was defined by aspiration, stricture, pneumonia, and/or gastrostomy dependence ≥12 months post-IMRT. Selective neck dissection was performed after IMRT in 75 patients (21%). Overall, 41 patients (12%) developed chronic dysphagia. Neck dissection did not increase the rate of chronic dysphagia (9% neck dissection; 12% no neck dissection; p = .464) or gastrostomy duration (p = .482). On multivariate analysis, age (odds ratio [OR] per 5-year = 1.25; 95% confidence interval [CI] = 1.04-1.51), baseline abnormal diet (OR = 2.78; 95% CI = 1.31-5.88), and IMRT dose (OR per 5-Gy = 5.11; 95% CI = 1.77-14.81) significantly predicted dysphagia. In the setting of selective neck dissection for residual adenopathy after IMRT, neck dissection did not impact dysphagia. © 2015 Wiley Periodicals, Inc. Head Neck 38: 886-893, 2016.

Late radiation-associated dysphagia (late-RAD) with lower cranial neuropathy after oropharyngeal radiotherapy: A preliminary dosimetric comparison

Late radiation-associated dysphagia (late-RAD) is a rare delayed toxicity, in oropharyngeal cancer (OPC) survivors. Prevention of late-RAD is paramount because the functional impairment can be profound and refractory to standard therapies. The objective of this analysis is to identify candidate dosimetric predictors of late-RAD and associated lower cranial neuropathies after radiotherapy (RT) or chemo-RT (CRT) for OPC. An unmatched retrospective case-control analysis was conducted. Late-RAD cases were identified among OPC patients treated with definitive RT or CRT. Controls were selected with minimum of 6 years without symptoms of late-RAD. Dysphagia-aspiration related structures (DARS) and regions of interest containing cranial nerve paths (RCCNPs) were retrospectively contoured. Dose volume histograms were calculated. Non-parametric bivariate associations were analyzed with Bonferroni correction and multiple logistic regression models were fit. Thirty-eight patients were included (12 late-RAD cases, 26 controls). Median latency to late-RAD was 5.8 years (range: 4.5-11.3 years). Lower cranial neuropathies were present in 10 of 12 late-RAD cases. Mean superior pharyngeal constrictor (SPC) dose was higher in cases relative to controls (median: 70.5 vs. 61.6 Gy). Mean SPC dose significantly predicted late-RAD (p = 0.036) and related cranial neuropathies (p = 0.019). RCCNPs did not significantly predict late-RAD or cranial neuropathies. SPC dose may predict for late-RAD and related lower cranial neuropathies. These data, and those of previous studies that have associated SPC dose with classical dysphagia endpoints, suggest impetus to constrain dose to the SPCs when possible.

Late Radiation-Associated Dysphagia (RAD) in Head and Neck Cancer Survivors

Head and neck cancer (HNC) survivors are living longer due to epidemiologic changes in the disease and advances in treatment. As a consequence, speech pathologists encounter growing numbers of long...