Dysphagia/aspiration Related Structures Research Articles

Acute radiation morbidities and dosimetric evaluation of DARS structures: Results from the phase III randomized SWOAR trial.

TPS149 Background: The SWOAR is a phase III trial (ClinicalTrials.gov ID NCT05187091) evaluating sparing of dysphagia/aspiration related structures (DARS) & submandibular gland by IMRT. Methods: Patients with T1-4, N0-3, M0 of oropharynx, larynx and hypopharynx treated with radical RT were randomized to arm A (standard IMRT) or arm B (DARS IMRT) in 1:1 manner. Treatment allocation was done based on T stage, concurrent chemotherapy use (weekly 40mg/m2) & subsite. A10-point improvement in MD Anderson Dysphagia Inventory (MDADI) composite score (primary end point of study) at 6 months post RT with SD of 17, power as 90% and two-sided alpha of 5% estimated sample size. SIB IMRT delivered dose of 66Gy (gross disease+0.5cm), 54Gy (gross disease+1cms+regional lymphatics) in 30 fractions. Acute radiation morbidities were scored by RTOG scoring criteria. Aspiration prevention assessment was done by PAS measured by FEES. Results: A total of 166 patients till date have been enrolled, 81 in Arm A & 85 in Arm B. Median age was 58 years, 73.4% had oropharyngeal primary, 89% had stage III-IV & received concurrent chemotherapy. Median composite MDADI scores pre-RT in Arm A was 70.5 (IQR 56.8-75.8) & 69.5 (56.8-75.8) in arm B. Post-RT median score dropped to 54.2 (48.8-60) in arm A & 54.8 (51.6-65.3) in arm B. Reduction in MDADI score pre & post RT in arm A was median 11.1 (0-21) & arm B was 7.9 (0-20) (p=0.28). Pre RT-PAS score was similar in both arms 1 (IOR 1-2), post-RT PAS in arm A was 1 (1-2) & arm B was 1 (1-1). Median of mean dose to SCM was 56.2Gy (46.8Gy-61.2Gy) vs 48.9Gy (36Gy-57.6Gy) p<0.003, MCM 58.5Gy (52.7Gy-63.1Gy) vs 56.2Gy (47.8-63.6) p=0.11, ICM 48.5Gy (46.8Gy-57.7Gy) vs 37.8Gy (26.5-62.4) p<0.001, base of tongue 60.5Gy (53.9Gy-64.3Gy) vs 53.9Gy (40.2Gy-62.4Gy) p=0.001,supraglottic larynx 57.7Gy (49.2Gy-64.4Gy) vs 60.5Gy (46.7-64.6) p=0.63, larynx 46.0Gy(42.4Gy-53.7Gy) vs 28.3Gy (21.5Gy-49Gy) p<0.001, cricopharyngeus 46.0Gy(43.6Gy-49.9Gy) vs 32.6Gy (27.3Gy-47Gy) p<0.001, esophageal inlet 44.6Gy (41.3Gy-47.9Gy) vs 27.2Gy (22.8Gy-39.1Gy) p<0.001, contralateral submandibular gland 52.8Gy (48.5Gy-57.2Gy) vs 40.4Gy (37.3-49.6) p<0.001, all arm A vs arm B respectively. Acute grade 3 occurred in 68.4% in arm A & 54.4% arm B, p=0.07. Acute grade 3 mucositis developed in 34.2% in arm A vs 16.7% arm B, p=0.009. Conclusions: Swallowing-sparing IMRT significantly reduced dose to contralateral submandibular gland & all the DARS structures (except middle constrictor muscle & supra glottic larynx). Dosimetric advantage gained by delivery of Swallowing-sparing IMRT resulted in significant reduction in development of acute grade III mucositis & showed a trend towards reduction in all acute grade III toxicities. Clinical trial information: NCT05187091 .

Impact of Radiation on Dysphagia-Related Structures: A Dosimetric and Clinical Comparative Analysis of Three-Dimensional Conformal Radiotherapy (3D-CRT) and Intensity-Modulated Radiation Therapy (IMRT) Techniques in Patients With Head and Neck Cancer.

Introduction Head and neck squamous cell carcinoma (HNSCC)is a significant health concern in India, with around one million new cases annually. The prevalence of HNSCC is notably high in Asia, especially in India, due to habitslike tobacco chewing, betel nut usage, and alcohol consumption. Treatment typically involves a combination of surgery, radiation, chemotherapy, and biological therapy, aiming for tumor control while preserving function and quality of life. However, survivors often face long-term side effectslike difficulty swallowing, leading to complicationssuch as aspiration pneumonia. Intensity-modulated radiotherapy (IMRT) has shown promise in improving outcomes by sparing critical swallowing structures. Efforts to minimize radiation-related dysphagia are crucial for enhancing patients' quality of life post-treatment. Our study focuses on examining dosimetric parameters associated with dysphagia aspiration, alongside evaluating dysphagia grades in both treatment groups using the RTOGscale. Material and methods Patients with histologically confirmed non-metastatic head and neck carcinomas were included in our study in November 2018-April 2020. A total of 56 patients were taken into our study with 28 in each arm. They underwent radical radiotherapy (RT) with a total dose of 66-70 Gy, with or without concurrent chemotherapy, meeting specific inclusion criteria and excluding those receiving reirradiation or with distant metastasis. Patients were divided into two groups: Group I received three-dimensional conformal radiotherapy (3D-CRT), and Group II received IMRT. Treatment planning involved immobilization, CT imaging, delineation of target volumes and organs at risk, and contouring of swallowing structures. Dose-volume histogram parameters (mean dose, maximum dose, V30, V70, V80, D50, and D80) were used to assess mean dose to swallowing structures outside the planning target volume (PTV), with a mean dose constraint of 50 Gy. Dysphagia was evaluated using the RTOGcriteria at baseline, during treatment, and six months post-treatment. Statistical analysis was performed using SPSS, with significance set at p < 0.05. Results In our study, the mean age at presentation differed slightly between the IMRT and 3D-CRT arms: 58 years versus 55 years, respectively. A higher proportion of patients in both arms experienced symptoms for three to six months, with 53.6% in 3D-CRT and 42.9% in IMRT. Stage distribution varied, with IV being most common in 3D-CRT and stage II in IMRT. Approximately 56% of patients in both groups had a history of smoking. Significant differences were observed in spinal cord dose between 3DCRT and IMRT techniques (p < 0.001). Similarly, a significant difference was found in the mean dose received by dysphagia aspiration-related structures (DARSs) between the 3D-CRT and IMRT arms (p = 0.04). Patients in the IMRT arm exhibited superior dysphagia grades compared to those in the 3D-CRT arm, with statistical significance observed in the third month (p = 0.008) and sixth month (p = 0.048). Conclusion Our study found a notable decrease in the mean DARS dose and reduced dysphagia severity at three and six months in the IMRT group compared to the 3D-CRT group. However, due to the diverse study population, establishing a definitive correlation between the DARS dose and dysphagia severity was challenging. Future large-scale studies are needed to validate these findings for improved preservation of DARS structures.

Feasibility of Achieving Dose Constraints for Dysphagia Aspiration-Related Structures and Its Clinical Significance in Intensity-Modulated Radiotherapy Planning of Head and Neck Cancer.

Introduction Dysphagia is commonly seen in patients with head and neck cancers after undergoing chemoradiotherapy and is often under-reported and also not given clinical importance. The quality of life of the patients can be significantly improved if the required dose constraints to the dysphagia aspiration-related structures (DARS) are achieved. The present study was conducted in order to determine the feasibility of achieving the dose constraints to DARS between the standard intensity-modulated radiotherapy(st-IMRT) arm and the dysphagia-optimized IMRT (do-IMRT) arm. Material and methods Sixty patients with head and neck cancer were recruited and randomized into two groups: In one group called the st-IMRT, constraints were not given to DARS, and in the other group called the do-IMRT, constraints were given to DARS. Treatment was given in the form of chemoradiation with a dose of 70 Gy in 35 fractions by IMRTtechnique, over seven weeks, 2 Gy per fraction along with weekly concurrent Cisplatin (35 mg/m2) in both the groups. Step and shoot IMRT setup was used for planning, and the system used forplanning was Eclipse 13.6 (Varian Medical System, Inc., Palo Alto, CA, US); progressive resolution optimizeralgorithm was used for optimization, and Anisotropic Analytical Algorithmalgorithm was used for dose calculation. Truebeam was used for treatment delivery. DARS dosimetric parameters assessed were Dmean, V30, V50, V60, V70, D50, and D80. Radiation-induced toxicities to the skin, mucosa, larynx, salivary gland, and dysphagiaand hematological toxicities were assessed in between both the groups during and after radiotherapy up to six months based on Common Terminology Criteria for Adverse Effects v5.0. p-values were calculatedusing the unpaired T-test. Results In the cohort of 60 patients with head and neck cancers, 95% were males. Dosimetric parameters of the planning target volume (PTV) were compared but were not found to be significant. In the dosimetry of the organs at risk, a p-value of some structures was found to be significant although the doses received were well within the tolerable limits in both arms. DARS dosimetry V60 and V70 of the inferior constrictor muscle was found to be statistically significant (p=0.01 and 0.008, respectively). V60 and V70 of larynx were also statistically significant (p=0.009 and 0.000, respectively). V70 and D50 of cricopharyngeus were found to be statistically significant (p=0.01 and 0.03, respectively), V30 and V60 for combined pharyngeal constrictor muscles were found to be statistically significant (p=0.02 and 0.01), and lastly, V60 for combined DARS was also significant (p=0.004). Post-treatment 33.3% of patients in the st-IMRT arm required Ryle's tube placement. No grade 4 toxicities were seen in either arm regarding hematological toxicities, acute or chronic radiation-induced toxicities. In site-wise comparison of doses, the p-value was not found to be significant in patients with oropharyngeal and oral cavity carcinomas but was found to be statistically significant in the larynx and hypopharynx subsites. Conclusion The feasibility of achieving dose constraints to the DARS was seen in cases of laryngeal and hypopharyngeal cancers where the constrictor muscles were at a distance from the PTV. Further, the feasibility of achieving dose constraints may be seen in lower-dose prescriptions either in postoperative cases or in low-risk clinical target volumenodal volumes.

Can dysphagia aspiration related structures (DARS) be spared in patients with oropharyngeal cancers? Dosimetric evaluation in a prospective study of DARS optimized intensity modulated radiation therapy

ABSTRACT Purpose: To evaluate the feasibility of sparing the dysphagia-aspiration-related structures (DARS) in various head and neck cancer sites treated with definitive DARS-optimized intensity modulated radiation therapy (IMRT) and concurrent chemotherapy. Materials and Methods: Target volumes, organs at risk, and in addition, individual DARS were delineated, including the superior, middle, and inferior pharyngeal constrictor muscles, supraglottic and glottic larynx, the base of the tongue, esophageal inlet muscles and cervical esophagus in 35 patients with head and neck squamous cell carcinoma. Volume-based dose constraints were applied to the DARS outside the planning target volume (PTV). An IMRT plan was then generated to limit doses to DARS without compromising PTV dose coverage. Results: Twelve (34.3%) patients had an oropharyngeal primary (OPX), 18 (51.4%) had a laryngeal, and 5 (14.3%) patients had hypopharyngeal primary. The mean dose to the DARS was 47.93 Gy for the entire group, while it was 54.6 Gy in oropharyngeal primaries and 44.4 Gy in laryngopharyngeal primaries. DARS mean dose of ≤45 Gy could be achieved in a significantly lesser number of patients with oropharyngeal primaries (P &lt; 0.02). Similarly, DARS mean dose was 42.25 Gy in patients with N0 disease, 49.6 Gy with ipsilateral involved nodes, and 55 Gy with bilateral disease. Sparing of DARS was feasible when the volume of PTV was ≤150 cc (P &lt; 0.025). Conclusion: Sparing of DARS structures appears to be challenging in patients with oropharyngeal cancers without compromising the dose to the PTVs while it is feasible in laryngopharyngeal cancers. DARS sparing is feasible when the PTV volume is &lt; 150 cc and in patients with negative or unilateral nodal disease.

Toxicities and clinical outcome of adjuvant dysphagia optimized versus standard intensity-modulated radiotherapy for post-operative oral cavity cancers: A prospective comparative study.

We prospectively assessed acute and late toxicity in post-operative oral cavity squamous cell carcinoma (PO-OCSCC) treated with adjuvant dysphagia optimized intensity-modulated radiotherapy (Do-IMRT) versus standard IMRT (S-IMRT). Fifty-six patients of PO-SCC without indications of concurrent chemotherapy were alternatively allocated to adjuvant Do-IMRT (n = 28) versus S-IMRT (n = 28) arms. High- and low-risk planning target volume received 60 and 54 Gy, respectively, in 30 fractions over 6 weeks. Dysphagia aspiration-related structures (DARS) were contoured in both arms. While dosimetric constraints were given in Do-IMRT arm, doses to DARS were only observed without dose constraints in S-IMRT arm. Acute and late toxicity were assessed by common terminology criteria for adverse events (CTCAE) v5.0 and RTOG criteria, respectively. The primary site of disease was buccal mucosa (64% vs. 53%) and oral tongue (21% vs. 32%), in Do-IMRT and S-IMRT, respectively. The mean doses to DARS was significantly less with Do-IMRT (all p < 0.001) as compared to S-IMRT. Median follow-up was 24.2 months. Grade ≥2 oral pain was less in the Do-IMRT arm (50% vs. 78.6%, p = 0.05). Grade ≥2 late dysphagia at 2 years were significantly less in Do-IMRT arm (0% vs. 17.9%, p = 0.016). Two-year locoregional control was 89.2% in Do-IMRT and 78.5% in S-IMRT (p = 0.261). DARS can be spared in PO-OCSCC patients treated with Do-IMRT without compromising coverage of the target volumes. Limiting doses to DARS leads to lesser acute and late toxicity without compromising locoregional control.

Simultaneous Modulated Accelerated Radiotherapy (SMART) with Dysphagia Aspiration-Related Structures (DARS) Sparing: Do We Have a Role for Dose Condensation in Locally Advanced Head and Neck Cancer

Introduction Concurrent chemotherapy integrated with intensity-modulated radiotherapy (IMRT) is the standard of care for locally advanced head and neck cancer. Simultaneous integrated boost technique has allowed differential doses to primary and normal structures permitting significant toxicity reduction. The current study explores the feasibility of the simultaneous modulated accelerated radiotherapy (SMART) technique to enhance cytoreduction and explore the possibility of dose intensification with radiobiologically targeted treatment condensation. Methods Thirty patients were randomized in an open-labeled study to receive concurrent chemoradiation of 60 Gy in 25 fractions with “SMART” technique or 70 Gy in 35 fractions using conventional intensity-modulated radiotherapy simultaneous integrated boost “IMRT SIB.” The primary endpoints included comparative volumetric cytoreduction between the study and control arm assessed during the course of treatment and final response evaluation. Secondary endpoints involved the assessment of acute toxicity parameters for xerostomia, mucositis, dysphagia, and fatigue. Results The “SMART” study arm showed comparable volumetric cytoreduction to the conventional “IMRT SIB” arm at midtreatment (p-value = 0.225) as well as toward completion (p-value = 0.476). The study arm did observe 94.4% cytoreduction of tumor volume compared with 88.05% in the conventional arm at the time of response evaluation. In spite of treatment condensation, there was no significant increase in toxicity with “SMART.” There was no difference in the frequency or duration of grade 3 mucositis in the “SMART” arm in spite of intensification (p-value = 0.728). In the “SMART” arm, there was a favorable reduction in the duration of grade ⅔ dysphagia; 2.8 weeks versus 4.6 weeks (p-value = 0.002). Even though the xerostomia was comparable in frequency and intensity, the total duration of xerostomia was 50% less (p-value = 0.001). Conclusions The “SMART” technique provides a radiobiologically sound, effective, and safe protocol that has the potential to improve the treatment of locally advanced head and neck cancer. The good tolerability and toxicity profile in the study arm is encouraging and facilitates further research.

Comparison of Dosimetric Parameters in Dysphagia Aspiration-Related Structures and Clinical Correlation in Head and Neck Cancer Patients Treated With Radiotherapy.

IntroductionChemoradiotherapy plays a major role in the treatment of head and neck cancer (HNC). Persistent dysphagia following primary chemoradiotherapy for head and neck cancers can have a devastating effect on a patient’s quality of life. Many studies have shown that the dosimetric sparing of critical structures which were included in swallowing such as the pharyngeal constrictor muscle and larynx can provide improved functional outcomes and better quality of life. However, there are no current randomized studies confirming the benefits of such swallowing-sparing strategies. The aim is to evaluate late dysphagia after chemoradiotherapy for head and neck cancer and to examine its correlation with clinical and dosimetric parameters.Materials and methodsThe period of this prospective study was from November 2018 to March 2020. Patients were divided randomly in 1:1 ratio into two groups, group 1 and group 2, each with 25 patients. Group 1 was planned by three-dimensional conformal radiotherapy (3D-CRT) technique and group 2 was planned by intensity-modulated radiotherapy technique (IMRT) technique. Treatment was delivered after approval of radiotherapy plan. To evaluate the dose to dysphagia aspiration-related structures (DARS), these structures were contoured and dose-volume histograms were generated. Various dosimetric parameters of DARS were evaluated. Swallowing status was clinically evaluated based on the Radiation Therapy Oncology Group and the Common Terminology Criteria for Adverse Events, version 5.ResultsA significant advantage was seen with intensity-modulated radiotherapy technique (IMRT) in comparison to three-dimensional conformal radiotherapy (3D-CRT) in terms of mean dose delivered to the pharyngeal constrictor muscles (66.03 Gy vs 68.77 Gy, p=0.003). The mean dose delivered to the combined dysphagia/aspiration-related structures (DARS) was statistically significantly lower in IMRT compared to 3D-CRT (66.15 Gy vs. 70.09 Gy, p<0.001). Other dose-volumes were also reduced in IMRT group (V30: {98.64% vs. 99.88%, p=0.05}; V50: {90.49% vs. 99.02%, p=0.0002}; V60: {83.92% vs. 95.04, p=0.0002}; D50: {70 Gy vs. 71.16 Gy, p=0.001); and D80: {61.18 Gy vs. 67.39 Gy, p=0.01}. Futhermore, the clinical worsening of dysphagia was less common in IMRT group (48% vs. 80%, p=0.039).ConclusionIMRT can reduce the high-dose volumes received by the DARS receiving high doses by sparing these structures through optimization. This may provide a significant additional benefit that could improve dysphagia and hence the quality of life of patients with head and neck cancer.

Quality of life and two-year results of a randomized phase III study of dysphagia-optimized intensity modulated radiotherapy (DO-IMRT) versus standard IMRT (S-IMRT) in head and neck cancer.

6065 Background: Most newly diagnosed oro- &amp; hypopharngeal cancers (OPC, HPC) are treated with (chemo)RT with curative intent but at the consequence of adverse effects on quality of life. We investigated if using DO-IMRT to reduce RT dose to the dysphagia/aspiration related structures (DARS) improved swallowing function compared to S-IMRT. Methods: Patients with T1-4, N0-3, M0 OPC/HPC were randomised 1:1 to S-IMRT (65 Gray (Gy)/30 fractions (f) to primary &amp; nodal tumour; 54Gy/30f to remaining pharyngeal subsite &amp; nodal areas at risk of microscopic disease) or DO-IMRT. The volume of the superior &amp; middle pharyngeal constrictor muscle (PCM) (OPC) or inferior PCM (HPC) lying outside the high-dose target volume was set a mandatory mean dose constraint in DO-IMRT. Treatment allocation was by minimisation balanced by centre, use of induction/concomitant chemotherapy, tumour site &amp; AJCC stage. Primary endpoint was mean MD Anderson Dysphagia Inventory (MDADI) composite score 12 months after RT. Secondary endpoints included University of Washington (UW)-Qol, Performance Status Scale Head &amp; Neck (PSS-HN) domain scores (range: 0-100), swallow volume, swallow capacity and local control. Results: 112 patients (56 S-IMRT, 56 DO-IMRT) were randomised from 22 UK &amp; Ireland centres from 06/2016 - 04/2018. 111/112 had RT doses as prescribed (1 patient died before RT). Outcome measures at 12 and 24 months are summarised below. DO-IMRT had higher MDADI scores at 12 (p = 0.04) and 24 (p = 0.07) months. Clinically important improvements in swallowing function were seen in patients receiving DO-IMRT using PSS-HN domains and the UW-QoL tool. Conclusions: DO-IMRT improved patient reported swallowing function compared with S-IMRT. Improvements were seen in overall MDADI as well as functional scores in both PSS-HN and UW-QoL. Clinical trial information: 25458988. [Table: see text]

Clinical Outcomes and Toxicity Profile With IMRT or Brachytherapy Boost in Oropharyngeal Malignancies: A Randomized, Open Label Study

Radical radiation therapy in oropharyngeal malignancies have a significant toxicity especially in relation to dose to dysphagia aspiration related structures (DARS), mucositis and aspiration which leads to prolonged overall treatment times, thereby, having an impact on survival outcomes. Interstitial Brachytherapy (ISBT) has significant role in reducing these toxicities, however, literature comparing Intensity modulated radiation therapy (IMRT) with Brachytherapy boost is lacking. Our study looks into the clinical outcomes and toxicity profile while comparing the two treatment modalities.A total of 70 patients diagnosed histopathologically as squamous carcinoma of oropharynx were randomized to receive radical radiation therapy with IMRT (n = 35) or IMRT with ISBT boost (n = 35). The total dose with IMRT was 70Gy and in ISBT, initial dose was 50Gy with IMRT followed by 24.5Gy dose (3.5Gy in 12 fractions). Patients were followed up as per institute protocol and assessed for a median follow-up of 36 months. Assessment of survival outcomes in terms of progression free survival (PFS) and overall survival (OS) were assessed. Toxicity profile was assessed as per CTCAE 4.0 criteria and quality of life was assessed as per EORTC-C30 and HN35 questionnaires. Dosimetric parameters for the target volumes were compared along with assessment of various important organs at risk (OAR).After a median follow up of 36 months, PFS was 86% vs 81% favoring ISBT arm (P = 0.032), however, there was no difference in overall survival. On assessment of toxicities, dysphagia and xerostomia were significantly reduced with ISBT boost with Grade II and III toxicities 12% and 18% vs 18% and 24% respectively. On QoL assessment, physical (P < 0.001) and social functioning (P = 0.012) favored ISBT boost. On symptom assessment, fatigue, dyspnea, appetite loss, speech problems, swallowing and pain was significantly reduced with ISBT boost. Dosimetric parameters showed significant dose reduction to DARS (P < 0.001) and parotid glands (P < 0.001) with ISBT boost.ISBT boost has shown to be effective in improving PFS, toxicity profile and quality of life outcomes in oropharyngeal malignancies in spite of technological advancements in form of IMRT. ISBT should be employed in treatment armamentarium to dose escalate and thereby improve survival especially in oropharyngeal malignancies.

Quality assurance of radiotherapy in the ongoing EORTC 1420 \u201cBest of\u201d trial for early stage oropharyngeal, supraglottic and hypopharyngeal carcinoma: results of the benchmark case procedure

IntroductionThe current phase III EORTC 1420 Best-of trial (NCT02984410) compares the swallowing function after transoral surgery versus intensity modulated radiotherapy (RT) in patients with early-stage carcinoma of the oropharynx, supraglottis and hypopharynx. We report the analysis of the Benchmark Case (BC) procedures before patient recruitment with special attention to dysphagia/aspiration related structures (DARS).Materials and methodsSubmitted RT volumes and plans from participating centers were analyzed and compared against the gold-standard expert delineations and dose distributions. Descriptive analysis of protocol deviations was conducted. Mean Sorensen-Dice similarity index (mDSI) and Hausdorff distance (mHD) were applied to evaluate the inter-observer variability (IOV).Results65% (23/35) of the institutions needed more than one submission to achieve Quality assurance (RTQA) clearance. OAR volume delineations were the cause for rejection in 53% (40/76) of cases. IOV could be improved in 5 out of 12 OARs by more than 10 mm after resubmission (mHD). Despite this, final IOV for critical OARs in delineation remained significant among DARS by choosing an aleatory threshold of 0.7 (mDSI) and 15 mm (mHD).ConclusionsThis is to our knowledge the largest BC analysis among Head and neck RTQA programs performed in the framework of a prospective trial. Benchmarking identified non-common OARs and target delineations errors as the main source of deviations and IOV could be reduced in a significant number of cases after this process. Due to the substantial resources involved with benchmarking, future benchmark analyses should assess fully the impact on patients’ clinical outcome.

PLEN04 Presentation Time: 2:00 PM: Clinical Outcomes and Toxicity Profile with IMRT or Brachytherapy Boost in Oropharyngeal Malignancies: A Randomized, Open Label Study

Purpose/Objective(s): Radical radiation therapy in oropharyngeal malignancies have a significant toxicity especially in relation to dose to dysphagia aspiration related structures (DARS), mucositis and aspiration which leads to prolonged overall treatment times, thereby, having an impact on survival outcomes. Interstitial Brachytherapy (ISBT) has significant role in reducing these toxicities, however, literature comparing Intensity modulated radiation therapy (IMRT) with Brachytherapy boost is lacking.

Clinico-Dosimetric Correlation Of Doses To Dysphagia Aspiration Related Structures (DARS) With Acute Toxicities In Post-Operative Patients Of Oral Cavity Carcinoma Treated With Dysphagia Optimized Versus Standard IMRT

Limiting the radiation dose to dysphagia aspiration related structures (DARS) may reduce toxicities in patients of oral cavity squamous cell carcinoma (OCSCC) treated with adjuvant radiotherapy. We analyzed acute toxicity in patients of OCSCC treated with adjuvant intensity modulated radiation therapy (IMRT) reducing the dose of radiation received by DARS: dysphagia optimized IMRT (Do-IMRT) and compared it with standard IMRT (S-IMRT: without dose constraints to DARS). Fifty OCSCC patients between 18-70 years of age were randomized in this prospective study to receive either adjuvant Do-IMRT or S-IMRT. None received concurrent chemoradiotherapy. Target volume was divided into high, intermediate and low risk areas receiving doses in the range of 60-66 Gy, 54-58 Gy, 51-56 Gy in 30-33 fractions over 6-6.5 weeks, respectively. In addition to the conventional organs at risk, dose constraints were given to DARS in Do-IMRT arm. The primary end point was acute toxicity evaluated by common terminology criteria for adverse events (CTCAE) version 5.0. Each arm had 25 patients. Median age was 46.5 years (range 28-74 years). Patient characteristics were balanced between two groups. Buccal mucosa: Tongue: other primary were seen in 72% vs. 48%:12% vs. 36%: 16% vs. 16% respectively in Do-IMRT vs. S-IMRT. Similarly, T1:T2:T3:T4 were 8% vs. 4%: 60% vs. 40%: 24% vs. 32%: 8% vs. 24%; N0:N1:N2 were 68% vs. 48%: 16% vs. 36%: 16% vs. 16% in Do-IMRT vs. S-IMRT arm. respectively. Lymphovascular invasion and peri-neural invasion were observed in 20% vs. 36% and 20% vs. 12% respectively in Do-IMRT vs. S-IMRT. There was a statistically significant difference in the mean doses to DARS in Do-IMRT vs. S-IMRT arm without compromising PTV coverage (Table 1). Grade 3 dysphagia was significantly lower in the Do-IMRT vs. S-IMRT group (0% vs. 16%; p = 0.067). Do-IMRT significantly delivers lesser doses to DARS as compared to S-IMRT and trended to lesser acute grade ≥3 dysphagia and grade ≥2 oral pain compared to S-IMRT. Longer follow up and correlation of late toxicities would better define the role of Do-IMRT compared to S-IMRT in post-operative OCSCC patients.Abstract 3845; Rest is summarized in Table 1Dosimetric AnalysisDo-IMRT (Mean ± SD)S-IMRT (Mean ± SD)P valuePTV-HR V9597.86±1.1797.57±1.530.463PTV-IR V9599.03±1.3198.59±1.280.402PTV-LR V9598.82±1.6198.92±1.120.809Superior constrictor43.24±7.1652.33±6.66<0.001Middle Constrictor40.33±5.9352.86±5.59<0.001Inferior Constrictor29.05±9.9248.76±7.10<0.001Supraglottic Larynx40.06±5.4253.86±5.60<0.001Glottic Larynx31.76±9.3747.54±7.51<0.001Cricopharyngeus33.77±11.9446.48±7.54<0.001Cervical esophagus22.12±15.2532.18±12.780.015Acute toxicityDo-IMRTS-IMRTp-valueDysphagia Grade ≥287%100%0.102Oral mucositis Grade ≥330.4%44%0.252Pharyngeal mucositis Grade ≥30%12%0.133Oral pain Grade ≥252.2%76%0.077Oropharyngeal pain Grade ≥256.5%72%0.207 Open table in a new tab

MRI- and CT-determined changes of dysphagia / aspiration-related structures (DARS) during and after radiotherapy.

The concept of dysphagia/aspiration-related structures (DARS) was developed against the background of severe late side effects of radiotherapy (RT) for head and neck cancer (HNC). DARS can be delineated on CT scans, but with a better morphological discrimination on magnetic resonance imaging (MRI). Swallowing function was analyzed by use of patient charts and prospective investigations and questionnaires. Seventeen HNC patients treated with intensity-modulated radiotherapy (IMRT) ± chemotherapy between 5/2012 - 8/2015 were included. Planning CT (computed tomography) scans and MRIs (magnetic resonance imaging) prior, during 40 Gray (Gy) radiotherapy and posttreatment were available and co-registered to delineate DARS. The RT dose of each DARS was calculated. Five patients were investigated posttreatment for swallowing function and assessed by means of various questionnaires for quality of life (QoL), swallowing, and voice function. By retrospective comparison of DARS volume, a significant change in four of eight DARS was detected over time. Three increased and one diminished. The risk of posttreatment dysphagia rose by every 1Gy above the mean dose (D mean) of RT to DARS. 7.5 was the risk factor for dysphagia in the first 6 months, reducing to 4.7 for months 6-12 posttreatment. For all five patients of the prospective part of swallowing investigations, a function disturbance was detected. These results were in contrast to the self-assessment of patients by questionnaires. There was neither a dose dependency of D mean DARS volume changes over time nor of dysphonia and no correlation between volume changes, dysphagia or dysphonia. Delineation of DARS on MRI co-registered to planning CT gave the opportunity to differentiate morphology better than by CT alone. Due to the small number of patients with complete MRI scans over time, we failed to detect a dose dependency of DARS and swallowing and voice disorder posttreatment.

Results of a randomized phase III study of dysphagia-optimized intensity modulated radiotherapy (Do-IMRT) versus standard IMRT (S-IMRT) in head and neck cancer.

6508 Background: Most newly diagnosed oro- &amp; hypopharngeal cancers (OPC, HPC) are treated with (chemo)RT with curative intent but at the consequence of adverse effects on quality of life. CRUK/14/014 investigated if using Do-IMRT to reduce RT dose to the dysphagia/aspiration related structures (DARS) improved swallowing function compared to S-IMRT. Methods: Patients with T1-4, N0-3, M0 OPC/HPC were randomised 1:1 to S-IMRT (65 Gray (Gy)/30 fractions (f) to primary &amp; nodal tumour; 54Gy/30f to remaining pharyngeal subsite &amp; nodal areas at risk of microscopic disease) or Do-IMRT. The volume of the superior &amp; middle pharyngeal constrictor muscle (PCM) (OPC) or inferior PCM (HPC) lying outside the high-dose target volume was set a mandatory mean dose constraint in Do-IMRT. Treatment allocation was by minimisation balanced by centre, use of induction/concomitant chemotherapy, tumour site &amp; AJCC stage. Primary endpoint was mean MD Anderson Dysphagia Inventory (MDADI) composite score 12 months after RT with 102 patients needed to detect a 10 point improvement (assuming S-IMRT score of 72, standard deviation (SD) 13.8; 90% power, 2-sided 5% alpha). Patients were blind to treatment allocation. Secondary endpoints included local control. Results: 112 patients (56 S-IMRT, 56 Do-IMRT) were randomised from 22 UK centres from 06/2016 to 04/2018. Mean age was 57 years; 80% were male; 97% had OPC; 90% had AJCC stage 3&amp;4 disease; 86% had concomitant chemotherapy only, 4% induction &amp; concomitant and 10% no chemotherapy. 111/112 had RT doses as prescribed (1 patient died before RT). Median of the mean inferior PCM dose was S-IMRT 49.8Gy (IQR 47.1-52.4) vs. Do-IMRT 28.4Gy (21.3–37.4), p &lt; 0.0001; superior &amp; middle PCM dose was S-IMRT 57.2Gy (56.3–58.3) vs. Do-IMRT 49.7Gy (49.4–49.9), p &lt; 0.0001. Do-IMRT had significantly higher MDADI scores: S-IMRT 70.3 (SD 17.3) vs. Do-IMRT 77.7 (16.1), p = 0.016. 3 local recurrences (1 S-IMRT, 2 Do-IMRT) have been reported. Conclusions: Do-IMRT reduced RT dose to the DARS and improved patient reported swallowing function compared with S-IMRT. This is the first randomised study to demonstrate functional benefit of swallow-sparing IMRT in OPC. Clinical trial information: 25458988 .

Perspectives on optimizing radiotherapy dose to the dysphagia/aspiration-related structures for patients with head and neck cancer.

The purpose of this study is to provide an overview on the methodologies, outcomes and clinical implications of studies that have investigated swallowing outcomes after head and neck cancer (HNC) treatment when reducing radiotherapy dose to specific dysphagia/aspiration-related structures (DARS). Overall, there is limited recent evidence, with a lack of high-quality studies, which examine the outcomes of DARS-optimized radiotherapy treatment. Large variations exist in the methodology of these studies in regards to which DARS are delineated and how swallowing outcomes are measured. Consequently, there is a wide range of dose limits recommended to a variety of DARS structures. Despite these limitations, there appears to be a general consensus that optimizing dose to the DARS will result in some reduction of dysphagia after radiotherapy without compromising on treatment to the tumour. More rigorous study must be completed to determine the true extent of clinical benefit from this practice. Institutions must take into consideration the limitations of the evidence as well as logistical costs of implementing this technique into practice. However, optimizing dose to the DARS appears to be a well-tolerated practice that may have substantial positive benefits for patients' swallowing function and quality of life after HNC treatment.

Sparing dysphagia/aspiration related structures using novel hybrid volumetric modulated arc therapy

PurposeStudies using split field IMRT to spare dysphagia/aspiration related structures (DARS) have raised concern regarding dose uncertainty at matchline. This study explores the utility of hybrid VMAT in sparing the DARS and assesses matchline dose uncertainty in postoperative oral cavity cancer patients and compares it with VMAT. Methods & materialsTen postoperative oral cavity cancer patients were planned with h-VMAT and VMAT using the same planning CT dataset. PTV and DARS were contoured using standard delineation guidelines. In h-VMAT 80% of the neck dose was planned using AP/PA technique and then VMAT optimization was done for the total PTV by keeping the corresponding AP/PA plan as the base dose. Planning goal for PTV was V95%≥95% and for DARS, adequate sparing. Plans and dose volume histograms were analyzed using dosimetric indices. Absolute point and portal dose measurements were done for h-VMAT plans to verify dose at the matchline. ResultsCoverage in both the techniques was comparable. Significant differences were observed in mean doses to DARS (Larynx: 24.36±2.51 versus 16.88±2.41Gy; p<0.0006, Pharyngeal constrictors: 25.16±2.41 versus 21.2±2.1Gy; p<0.005, Esophageal inlet: 18.71±2 versus 12.06±0.79Gy; p<0.0002) favoring h-VMAT. Total MU in both the techniques was comparable. Average percentage variations in point dose measurements in h-VMAT done at +3.5 and −3.5 positions were (1.47±1.48 and 2.28±1.35%) respectively. Average gamma agreement for portal dose measured was 97.07%. Conclusionh-VMAT achieves better sparing of DARS with no matchline dose uncertainty. Since these patients have swallowing dysfunction post-operatively, attempts should be made to spare these critical structures as much as possible.

Dysphagia-optimised Intensity-modulated Radiotherapy Techniques in Pharyngeal Cancers: Is Anyone Going to Swallow it?

Dysphagia after primary chemoradiotherapy or radiation alone in pharyngeal cancers can have a devastating impact on a patient’s physical, social and emotional state. Establishing and validating efficient dysphagia-optimised radiotherapy techniques is, therefore, of paramount importance in an era where health-related quality of life measures are increasingly influential determinants of curative management strategies, particularly as the incidence of good prognosis, human papillomavirus-driven pharyngeal cancer in younger patients continues to rise. The preferential sparing achievable with intensity-modulated radiotherapy (IMRT) of key swallowing structures implicated in post-radiation dysfunction, such as the pharyngeal constrictor muscles (PCM), has generated significant research into toxicity-mitigating strategies. The lack of randomised evidence, however, means that there remains uncertainty about the true clinical benefits of the dosimetric gains offered by technological advances in radiotherapy. As a result, we feel that IMRT techniques that spare PCM cannot be incorporated into routine practice. In this review, we discuss the swallowing structures responsible for functional impairment, analyse the studies that have explored the dose–response relationship between these critical structures and late dysphagia, and consider the merits of reported dysphagia-optimised IMRT (Do-IMRT) approaches, thus far. Finally, we discuss the dysphagia/aspiration-related structures (DARS) study (ISRCTN 25458988), which is the first phase III randomised controlled trial designed to investigate the impact of swallow-sparing strategies on improving long-term function. To maximise patient benefits, improvements in radiation delivery will need to integrate with novel treatment paradigms and comprehensive rehabilitation strategies to eventually provide a patient-centric, personalised treatment plan.

Radiation dose to dysphagia aspiration-related structures and its effect on swallowing: Comparison of three-dimensional conformal radiotherapy and intensity-modulated radiation therapy plans.

Radiotherapy techniques have improved over years but have also raised concerns over subsequent acute and late effects. One such complication, dysphagia, has led to much interest and optimization in treatment delivery. The aim of this study was to compare radiation dose to dysphagia aspiration related structures (DARS) in intensity modulated radiation therapy (IMRT) and three-dimensional conformal radiotherapy (3DCRT), and assess its relation to post-treatment swallowing status, in patients of carcinoma of the anterior two thirds of tongue. Treatment plans of patients treated with IMRT and 3DCRT, from November 2011 to December 2012, were retrieved. Swallowing structures were contoured. Dose volume histograms were generated. Constraint doses were considered based on the statistical derivations. Swallowing status was evaluated based on University of Washington Head- and Neck-related Quality-of-Life questions addressing swallowing. IBM SPSS Statistics 20 Windows (SPSS Inc., Chicago, IL, USA) was used. Mann-Whitney U-test, Spearman's rho correlation coefficient, and receiver operating curves were used. Definitive statistical and subjective correlations were found to exist between doses of swallowing structures, especially the constrictor muscles, the base of the tongue and larynx. Probable mean dose constraints derived statistically clinically corroborates with the swallowing status of patients. IMRT had statistically significant advantage over 3DCRT, in terms of V30 (P - 0.051), V50 (P - 0.002), V60 (P - 0.002), and D80 (P - 0.023) for swallowing structures taken together. Our study is probably one of the few studies predicting possible mean dose constraints for superior constrictor, the base of the tongue and larynx. Further prospective studies are required to confirm these and to improve the swallowing quality.

CT measurement of prevertebral soft tissue (PVST) and epiglottis as a predictor of swallowing dysfunction in head and neck cancer (HNC).

e17061 Background: Surgery & radiation cause soft tissue damage resulting in lymphedema and fibrosis (LEF). LEF of Dysphagia/Aspiration Related Structures (DARS) may result in late swallowing abnor...

Analysis of Dysphagia Patterns Using a Modified Barium Swallowing Test Following Treatment of Head and Neck Cancer.

PurposeThe purposes of this study were to evaluate specific dysphagia patterns and to identify the factors affecting dysphagia, especially aspiration, following treatment of head and neck cancer.Materials and MethodsA retrospective analysis of 57 patients was performed. Dysphagia was evaluated using a modified barium swallow (MBS) test. The MBS results were rated on the 8-point penetration-aspiration scale (PAS) and swallowing performance status (SPS) score.ResultsReduced base of the tongue (BOT) retraction (64.9%), reduced laryngeal elevation (57.9%), and cricopharyngeus (CP) dysfunction (47.4%) were found. Reduced BOT retraction was correlated with clinical stage (p=0.011) and treatment modality (p=0.001). Aspiration in 42.1% and penetration in 33.3% of patients were observed. Twenty-four patients had PAS values over 6, implying aspiration. Forty-one patients had a SPS score of more than 3, 25 patients had a score greater than 5, and 13 patients had a SPS score of more than 7. Aspiration was found more often in patients with penetration (p=0.002) and in older patients (p=0.026). In older patients, abnormal swallowing caused aspiration even in those with a SPS score of more than 3, irrespective of stage or treatment, contrary to younger patients. Tube feeders (n=20) exhibited older age (65.0%), dysphagia/aspiration related structures (DARS) primaries (75.0%), higher stage disease (66.7%), and a history of radiotherapy (68.8%).ConclusionReduced BOT retraction was the most common dysphagia pattern and was correlated with clinical stage and treatment regimens including radiotherapy. Aspiration was more frequent in patients who had penetration and in older patients. In contrast to younger patients, older patients showed greater risk of aspiration even with a single abnormal swallowing irrespective of stage or treatment.