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

Article

作者: Manam, Surendra ; Azharuddin, S K ; Pb, Anand Rao ; Teja, Ravi

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 habits like 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 effects like difficulty swallowing, leading to complications such 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 RTOG scale. 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 RTOG criteria 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.

2023-12-01·Head & neck

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

Article

作者: Agarwal, Akash ; Mishra, Vachaspati Kumar ; Sharma, Vikas ; Gandhi, Ajeet Kumar ; Sapru, Shantanu ; Srivastava, Anoop Kumar ; Khurana, Rohini ; Mishra, Surendra Prasad ; Rastogi, Madhup ; Patni, Ayushi ; Hadi, Rahat

Abstract:

Background:

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).

Material and methods:

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.

Results:

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).

Conclusion:

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.

2022-02-01·Head & neck2区 · 医学

Functional swallowing outcomes related to radiation exposure to dysphagia and aspiration‐related structures in patients with head and neck cancer undergoing definitive and postoperative intensity‐modulated radiotherapy

2区 · 医学

Article

作者: Freeman‐Sanderson, Amy ; Sullivan, Tom ; Milross, Chris ; McCabe, Natalie ; Wu, Raymond ; Charters, Emma ; Ballard, Kirrie ; Britton, Rafe ; Clark, Jonathan ; Bogaardt, Hans ; Davis, Hannah

Abstract:

Background:

The relationship between swallowing outcomes and radiotherapy dose to dysphagia and aspiration‐related structures (DARS) may be different following definitive versus postoperative radiotherapy (PORT) for mucosal head and neck cancer (HNC) and has not been well‐studied.

Method:

Patient‐ and clinician‐reported swallowing measures were prospectively collected at six time points from baseline to 24 months postradiotherapy HNC. Radiotherapy plans were retrospectively analyzed to assess dose delivered to DARS. The association between swallowing outcomes and participant demographics, tumor characteristics, and radiotherapy dose in definitive and postoperative treatment cohorts was assessed.

Results:

Ninety‐three participants who received radiotherapy for HNC were included in the analysis (n = 49 definitive radiotherapy for laryngeal/pharyngeal primary tumors and n = 44 postoperative PORT for predominantly oral cavity/salivary gland tumors). Participants undergoing PORT had lower doses to DARS than those undergoing definitive RT. High dose to the pharyngeal constrictors and base of tongue for definitive RT and the esophageal inlet, supraglottic larynx and cervical esophagus for the PORT group were associated with worse swallowing function.

Conclusion:

Radiation dose to DARS is associated with post‐treatment swallowing outcomes. These dose/outcome relationships may vary between the definitive and postoperative settings.

项与 ATYR-0101 相关的新闻（医药）

2024-11-15

·GlobeNewswire-Health Care

aTyr Pharma to Present Posters on tRNA Synthetase Candidate ATYR0101 at Keystone Symposia on Fibrosis

SAN DIEGO, Nov. 15, 2024 (GLOBE NEWSWIRE) -- aTyr Pharma, Inc. (Nasdaq: ATYR) (“aTyr” or the “Company”), a clinical stage biotechnology company engaged in the discovery and development of first-in-class medicines from its proprietary tRNA synthetase platform, today announced that the Company will present two posters related to its tRNA synthetase candidate ATYR0101 at the Keystone Symposia on Fibrosis: Inflammation, Drivers, and Therapeutic Resolution, which is scheduled to take place December 8 – 11, 2024, in Whistler, British Columbia, Canada. Details of the presentations appear below. The posters will be available on the aTyr website once presented. Title: A Newly Evolved Domain of Asp-tRNA Synthetase Interacts with Latent Transforming Growth Factor Beta Binding Protein 1 (LTBP-1) to Induce Myofibroblast ApoptosisAuthors: Ying-Ting Wang, Kristina Hamel, Andrew Imfeld, Yeeting E. Chong, Kaitlyn Rauch, Wayne Liu, Ryan A. Adams, Leslie Nangle. aTyr Pharma, San Diego, CA.Poster Number: 1046Session: Poster Session #1Date and Time: Monday, December 9, 2024, at 7:30 p.m. PST Title: Anti-Fibrotic Activity Observed Across Preclinical Models of Pulmonary and Renal Fibrosis for a Potential Therapeutic Based on Asp-tRNA SynthetaseAuthors: Alison Barber, Clara Polizzi, Jasmine Stamps, Max Pastenes, Ryan A. Adams, Christoph Burkart, Leslie Nangle. aTyr Pharma, San Diego, CA.Poster Number: 1045Session: Poster Session #1Date and Time: Monday, December 9, 2024, at 7:30 p.m. PST About aTyr aTyr is a clinical stage biotechnology company leveraging evolutionary intelligence to translate tRNA synthetase biology into new therapies for fibrosis and inflammation. tRNA synthetases are ancient, essential proteins that have evolved novel domains that regulate diverse pathways extracellularly in humans. aTyr’s discovery platform is focused on unlocking hidden therapeutic intervention points by uncovering signaling pathways driven by its proprietary library of domains derived from all 20 tRNA synthetases. aTyr’s lead therapeutic candidate is efzofitimod, a first-in-class biologic immunomodulator in clinical development for the treatment of interstitial lung disease, a group of immune-mediated disorders that can cause inflammation and progressive fibrosis, or scarring, of the lungs. For more information, please visit www.atyrpharma.com. Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements are usually identified by the use of words such as “anticipate,” “believes,” “designed,” “can,” “expects,” “intends,” “may,” “plans,” “potential,” “will,” and variations of such words or similar expressions. We intend these forward-looking statements to be covered by such safe harbor provisions for forward-looking statements and are making this statement for purposes of complying with those safe harbor provisions. These forward-looking statements include, among others, statements regarding the research and development activities related to and the potential therapeutic benefits and applications of our current and future product candidates, including ATYR0101. These forward-looking statements also reflect our current views about our plans, intentions, expectations, strategies and prospects, which are based on the information currently available to us and on assumptions we have made. Although we believe that our plans, intentions, expectations, strategies and prospects, as reflected in or suggested by these forward-looking statements, are reasonable, we can give no assurance that the plans, intentions, expectations, strategies or prospects will be attained or achieved. All forward-looking statements are based on estimates and assumptions by our management that, although we believe to be reasonable, are inherently uncertain. Furthermore, actual results may differ materially from those described in these forward-looking statements and will be affected by a variety of risks and factors that are beyond our control including, without limitation, uncertainty regarding geopolitical and macroeconomic events, risks associated with the discovery, development and regulation of our product candidates, the risk that we or our partners may cease or delay preclinical or clinical development activities for any of our existing or future product candidates for a variety of reasons (including difficulties or delays in patient enrollment in planned clinical trials), the possibility that existing collaborations could be terminated early, and the risk that we may not be able to raise the additional funding required for our business and product development plans, as well as those risks set forth in our most recent Annual Report on Form 10-K, Quarterly Reports on Form 10-Q and in our other SEC filings. Except as required by law, we assume no obligation to update publicly any forward-looking statements, whether as a result of new information, future events or otherwise. Contact: Ashlee Dunston Director, Investor Relations and Public Affairs adunston@atyrpharma.com

100 项与 ATYR-0101 相关的药物交易

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