A Study to Assess the Preservation of Hearing Function in Cochlear Sparing Radiation Therapy in Patients of Head and Neck Carcinoma Treated with Definitive Concomitant Chemo-Radiation

e-ISSN: 0976-822X, p-ISSN:2961-6042 Available online on http://www.ijcpr.com/ International Journal of Current Pharmaceutical Review and Research 2025; 17(9); 665-670 Banerjee et al. International Journal of Current Pharmaceutical Review and Research 665 Original Research Article A Study to Assess the Preservation of Hearing Function in Cochlear Sparing Radiation Therapy in Patients of Head and Neck Carcinoma Treated with Definitive Concomitant Chemo-Radiation Diya Banerjee1, Shampa Maity2, Apurba Bikash Pramanik3, Subrata Chatterjee4, Prasanta Kumar Gure5, Saptarshi Banerjee6 1Senior Resident, MD (Radiation Oncology), Department of Radiation Oncology, Acharya Harihar Post Graduate Institute of Cancer, Cuttack, Odisha 753007 2Assistant Professor, MD (Radiation Oncology), Department of Radiation Oncology, Murshidabad Medical College and Hospital, Berhampore, West Bengal 742101 3Associate Professor, MD (General Medicine), DM (Cardiology), Department of General Medicine, Deben Mahata Government Medical College & Hospital, Purulia, West Bengal 700064 4Professor, MD (Radiation Oncology), Department of Radiation Oncology, Medical College & Hospital, Kolkata, West Bengal 700073 5Associate Professor, MS (ENT), Department of ENT, Medical College & Hospital, Kolkata, West Bengal 700073 6Assistant Professor, MD (Radiation Oncology), Department of Radiation Oncology, Medical College & Hospital, Kolkata, West Bengal 700073 Received: 01-07-2025 / Revised: 16-08-2025 / Accepted: 26-08-2025 Corresponding Author: Dr. Apurba Bikash Pramanik Conflict of interest: Nil Abstract Introduction: Head and neck carcinoma (HNC) is commonly treated with definitive concomitant chemoradiation (CCRT), which, while effective, can result in significant treatment-related toxicities, including sensorineural hearing loss due to radiation exposure of the cochlea. Aims: Cochlear-sparing radiation therapy (CSRT) aims to reduce radiation dose to the cochlea while maintaining tumor control, potentially preserving hearing function. Methods: This study is a single-institutional prospective observational study conducted at the Department of Radiotherapy, Medical College and Hospital, Kolkata, from October 2022 to February 2024. The study population included patients attending the radiotherapy outpatient department with biopsy-proven locally advanced carcinoma of the head and neck, who had good performance status and satisfactory cardiological status, and were planned to receive concurrent chemoradiotherapy as definitive treatment. Results: Bone-masked pure tone audiometry showed that cochlear-sparing chemoradiation therapy led to frequencyand time-dependent increases in hearing thresholds. At 250 Hz, thresholds increased slightly immediately post-treatment and rose progressively at 3 and 6 months, reaching highly significant levels (up to 5.86 dB, p < 0.001). At 500 Hz, immediate changes were minimal, but significant threshold shifts were observed at 3 and 6 months (up to 4.11 dB, p < 0.001). At 1000 Hz, immediate post-treatment changes were negligible, while significant increases occurred at 3 and 6 months (up to 3.61 dB, p < 0.001). Linear regression revealed a dose-dependent relationship between cochlear maximum radiation doses (Dmax) and hearing thresholds over time, with stronger correlations at 3 and 6 months across all frequencies, indicating that higher cochlear doses are associated with greater long-term hearing loss. Conclusion: Cochlear-sparing radiation therapy during definitive CCRT for head and neck carcinoma is feasible and effectively preserves hearing function, particularly in lowto mid-frequency ranges, without compromising oncologic outcomes. Implementation of cochlear dose constraints in radiotherapy planning should be considered to minimize ototoxicity in HNC patients. Keywords: Head and neck carcinoma, cochlear-sparing radiotherapy, hearing preservation, chemo-radiation, sensorineural hearing loss, intensity-modulated radiation therapy (IMRT). This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided original work is properly credited. Introduction Head and neck carcinomas (HNCs), encompassing malignancies of the oral cavity, pharynx, larynx, and nasopharynx, represent a significant clinical challenge. The standard treatment for locally International Journal of Current Pharmaceutical Review and Research e-ISSN: 0976-822X, p-ISSN: 2961-6042 Banerjee et al. International Journal of Current Pharmaceutical Review and Research 666 advanced HNC often involves definitive concurrent chemoradiotherapy (CCRT), combining radiation therapy (RT) with chemotherapy, typically using cisplatin as a radiosensitizer [1]. While this approach has markedly improved survival rates, it is associated with a spectrum of acute and longterm toxicities, notably sensorineural hearing loss (SNHL). The cochlea, being a radiosensitive organ, is particularly vulnerable to radiation-induced damage, leading to irreversible hearing impairment in many patients [2]. The cochlea's anatomical location within the temporal bone and its intricate structure make it challenging to spare during radiation treatment [3]. Traditional radiotherapy techniques often result in significant exposure of the cochlea to therapeutic doses. However, advancements in radiation delivery, particularly intensity-modulated radiation therapy (IMRT), have enabled more precise targeting of tumor volumes while minimizing the dose to surrounding healthy tissues, including the cochlea [4]. Studies have demonstrated that IMRT can effectively reduce the cochlear dose, thereby preserving hearing function without compromising oncologic outcomes [5]. Despite these advancements, the risk of SNHL remains a concern, especially when combined with the ototoxic effects of cisplatin. Research indicates that cisplatin-induced hearing loss (CIHL) is dosedependent and may be exacerbated by concurrent RT [6]. Notably, a study comparing RT and CCRT patients found a significantly higher incidence of SNHL in the CCRT group, with cochlear doses exceeding 50 Gy correlating with increased hearing loss [7]. The cumulative ototoxic effects of RT and chemotherapy necessitate a reevaluation of treatment planning strategies. Implementing cochlear-sparing techniques in RT planning is imperative to mitigate the risk of SNHL. Emerging data suggest that optimizing radiation plans to minimize cochlear dose is feasible and can be achieved without compromising tumor control [8]. For instance, studies have shown that cochleasparing optimized radiotherapy for nasopharyngeal carcinoma can significantly reduce cochlear dose beyond current QUANTEC constraints, leading to improved hearing preservation [9]. Furthermore, advancements in imaging and treatment planning technologies, such as synthetic MRI-aided autodelineation for cone-beam CT-guided adaptive radiotherapy, have enhanced the precision of cochlear sparing. These technologies facilitate accurate delineation of the cochlea and other organs-at-risk, enabling more effective sparing and potentially reducing the incidence of SNHL [10]. In light of these considerations, this study aims to assess the preservation of hearing function in patients with HNC undergoing definitive CCRT utilizing cochlear-sparing radiation therapy techniques. By evaluating audiological outcomes and correlating them with dosimetric data, the study seeks to establish evidence-based guidelines for cochlear dose constraints and inform clinical practice to enhance the quality of life for HNC patients post-treatment. Materials and Methods Study Design: A single institutional prospective observational study. Place of study: Department of Radiotherapy, Medical College and Hospital, Kolkata. Period of study: The period of the study will be from October 2022 to February 2024. Study Population: Patients attending the radiotherapy OPD of Medical College and Hospital with biopsy proven Locally Advanced carcinoma of Head and Neck with good performance status and good cardiological status who will receive Concurrent Chemoradiotherapy as definitive treatment. Study Variables • Dependant variable • pre-treatment • Paired T tests Inclusion Criteria • Patients with histologically proven carcinoma of nasopharynx, oropharynx, laryngopharynx, larynx, oral cavity, salivary glands, paranasal sinuses, in their locally advanced stage (IIIIVA) who will be treated by conformal Radiotherapy along with concurrent cisplatin. • Male and female patients between the age of 18 to 65 years. • Adequate performance status (Karnofsky performance score 70 or more). • Haematological, renal, hepatic function within normal limit. • Baseline audiogram and speech discrimination score demonstrating good cochlear reserve. • Provision of informed consent. • Patients willing to attend OPD for long term follow up Exclusion Criteria • Prior chemotherapy or radiotherapy for the present disease. • Evidence of uncontrolled co-morbid condition(s) (Uncompensated respiratory, cardiac, hepatic and renal disease). • Poor cochlear reserve. • Patients unwilling for follow-up. Statistical Analysis: All collected and properly tabulated data are to be analyzed using standard International Journal of Current Pharmaceutical Review and Research e-ISSN: 0976-822X, p-ISSN: 2961-6042 Banerjee et al. International Journal of Current Pharmaceutical Review and Research 667 statistical software SPSS. Descriptive statistical parameters will be recorded and analyzed. Result Table 1: Paired T tests of hearing thresholds as measured by bone masked pure tone audiometries before and after treatments at specific intervals are: For left ear: Paired Differences Sig. (2Tailed) Mean Std. Deviati on Std. Error Mean Lower Upper t d f pre-treatment 250Hz and immediate post treatment -0.417 1.22766 0.20461 -0.832 -0.00129 -2.036 3 5 0.049 pre-treatment 250Hz and post -1.417 2.40684 0.40114 -2.231 -0.60231 -3.532 3 5 0.001 pre-treatment 250Hz and post -5.861 4.1207 0.68678 -7.255 -4.46687 -8.534 3 5 0 pre-treatment 500Hz and immediate post -0.417 1.40153 0.23359 -0.891 0.05754 -1.784 3 5 0.083 pre-treatment 500Hz and post 3 months 500Hz -1.417 2.40684 0.40114 -2.231 -0.60231 -3.532 3 5 0.001 pre-treatment 500Hz and post 6 months 500Hz -4.111 3.89709 0.64951 -5.43 -2.79253 -6.33 3 5 0 pre-treatment 1000Hz and immediate post -0.056 0.41019 0.06836 -0.194 0.08323 -0.813 3 5 0.422 pre-treatment 1000Hz and post 3 months -3.611 2.58874 0.43146 -4.487 -2.73521 -8.37 3 5 0 Table 2: Statistically significant hearing loss has been noticed for all measured frequencies (viz 250Hz, 500Hz, 1000Hz, 2000Hz, 4000Hz and 8000Hz) at 3rd and 6th months post-treatment Paired Differences Sig. (2Tailed) Mean Std. Deviatio n Std. Error Mean Interval of the Difference t df Lower Upper pre-treatment 250Hz and immediate post treatment 250Hz -0.556 1.59364 0.26561 -1.095 -0.01635 -2.092 35 0.044 pre-treatment 250Hz and post 3 months 250Hz -2.5 3.04725 0.50787 -3.531 -1.46896 -4.922 35 0 pre-treatment 250Hz and post 6 months 250Hz -5.861 4.04371 0.67395 -7.229 -4.49292 -8.697 35 0 pre-treatment 500Hz and immediate post treatment 500Hz 0 1.85164 0.30861 -0.627 0.6265 0 35 1 International Journal of Current Pharmaceutical Review and Research e-ISSN: 0976-822X, p-ISSN: 2961-6042 Banerjee et al. International Journal of Current Pharmaceutical Review and Research 668 Table 3: Linear regression to show correlation between Dmax (considered as independent variable in each case) and PTA score (the dependant variable) for different frequencies for the left ear are tabulated as under Dependant variable R2 Adjusted R P value Equation Square Immediate Post treatment 250Hz 0.003 -0.026 0.745 post3mo250Hz 0.213 0.19 0.005 Considering y=(m)x+c: PTA score = (0.001) × dmax+ 13.373 post6mo250Hz 0.506 0.491 0 Considering y=(m)x+c: PTA score = (0.003) × dmax+15.950 Immediate Post treatment 250Hz 0.041 0.013 0.237 post3mo500Hz 0.213 0.19 0.005 Considering y=(m)x+c: PTA score = (0.001) × dmax+ 13.373 post6mo500Hz 0.531 0.517 0 Considering y=(m)x+c: PTA score = (0.003) × dmax+14.059 immediate post treatment 1000Hz 0.014 -0.015 0.49 post3mo1000Hz 0.266 0.244 0.001 Considering y=(m)x+c: PTA score = (0.002) × dmax+18.983 post6m1000Hz 0.57 0.558 0 Considering y=(m)x+c: PTA Hearing thresholds measured by bone-masked pure tone audiometry showed a statistically significant increase at lower frequencies following cochlearsparing chemoradiation therapy. At 250 Hz, the immediate post-treatment mean threshold increased slightly by 0.42 dB, which was borderline significant (t = –2.036, p = 0.049). At 3 months post-treatment, the mean threshold increased by 1.42 dB (t = –3.532, p = 0.001), and at 6 months, a more pronounced increase of 5.86 dB was observed, which was highly significant (t = –8.534, p < 0.001). Similarly, at 500 Hz, immediate posttreatment changes were not statistically significant (–0.42 dB, t = –1.784, p = 0.083), whereas thresholds at 3 months and 6 months increased by 1.42 dB (t = –3.532, p = 0.001) and 4.11 dB (t = – 6.33, p < 0.001), respectively. At 1000 Hz, immediate post-treatment changes were minimal and not significant (–0.056 dB, t = –0.813, p = 0.422), but at 3 months post-treatment, the mean threshold increased by 3.61 dB, showing a highly significant change (t = –8.37, p < 0.001). Bone-masked pure tone audiometry demonstrated frequencyand time-dependent changes in hearing thresholds following cochlear-sparing chemoradiation therapy. At 250 Hz, the immediate post-treatment mean threshold increased by 0.56 dB, which was statistically significant (t = –2.092, p = 0.044). At 3 months post-treatment, the mean threshold increased by 2.50 dB (t = –4.922, p < 0.001), and at 6 months, a more pronounced increase of 5.86 dB was observed (t = –8.697, p < 0.001). At 500 Hz, immediate post-treatment changes were negligible, with a mean difference of 0 dB, showing no statistical significance (t = 0, p = 1). Bone-masked pure tone audiometry demonstrated frequencyand time-dependent changes in hearing thresholds following cochlear-sparing chemoradiation therapy. At 250 Hz, immediate post-treatment thresholds increased slightly by 0.56 dB, which was statistically significant (t = –2.092, p = 0.044), and more pronounced increases were observed at 3 months (2.50 dB, t = –4.922, p < 0.001) and 6 months (5.86 dB, t = –8.697, p < 0.001). At 500 Hz, immediate post-treatment changes were negligible (0 dB, t = 0, p = 1), while increases at 3 months (1.42 dB, t = –3.532, p = 0.001) and 6 months (4.11 dB, t = –6.33, p < 0.001) were significant. At 1000 Hz, immediate posttreatment changes were minimal (–0.056 dB, t = – 0.813, p = 0.422), but significant increases were noted at 3 months (3.61 dB, t = –8.37, p < 0.001). Linear regression analysis showed that hearing thresholds progressively correlated with cochlear maximum radiation dose (Dmax) over time. Immediate post-treatment thresholds at all frequencies were not significantly associated with Dmax; however, at 3 and 6 months, significant dose-dependent relationships emerged. For 250 Hz, PTA scores increased as PTA = 0.001 × Dmax + 13.373 at 3 months and PTA = 0.003 × Dmax + 15.950 at 6 months (R² = 0.213 and 0.506, p = 0.005 and <0.001, respectively). At 500 Hz, significant correlations appeared at 3 months (PTA = 0.001 × Dmax + 13.373, R² = 0.213, p = 0.005) and 6 months (PTA = 0.003 × Dmax + 14.059, R² = 0.531, p < 0.001). For 1000 Hz, thresholds correlated with Dmax at 3 months (PTA = 0.002 × International Journal of Current Pharmaceutical Review and Research e-ISSN: 0976-822X, p-ISSN: 2961-6042 Banerjee et al. International Journal of Current Pharmaceutical Review and Research 669 Dmax + 18.983, R² = 0.266, p = 0.001) and 6 months (R² = 0.57, p < 0.001). Discussion Our study assessed cochlear-sparing radiation therapy in head and neck carcinoma patients undergoing definitive chemoradiation. We observed significant increases in hearing thresholds over time, particularly at lower frequencies, which aligns with findings from previous research [1,2]. Linear regression analysis revealed a dosedependent relationship between cochlear radiation dose (Dmax) and hearing thresholds, consistent with studies that identified significant factors influencing hearing threshold shifts in patients receiving chemoradiotherapy [3,4]. Kitoh et al. reported greater threshold increments at higher frequencies, which is relevant when considering timing and frequency-specific monitoring [5]. Cochlea-sparing techniques have been shown to reduce hearing loss without compromising tumor control, as demonstrated in optimized IMRT planning studies [6,7]. In contrast, other studies reported adverse cochlear effects when conventional radiation techniques were used, emphasizing the importance of precise treatment planning [8,9]. Collectively, our findings corroborate existing literature on the detrimental effects of chemoradiation on hearing function. The observed dose-dependent relationship underscores the necessity for meticulous cochlear-sparing strategies to mitigate ototoxicity. Future research should focus on refining these techniques and exploring interventions to preserve hearing in this patient population [10]. Conclusion Cochlear-sparing radiation therapy in patients with head and neck carcinoma undergoing definitive chemoradiation effectively preserves hearing function, particularly at higher frequencies, while still allowing optimal tumor dose delivery. Our study demonstrated that hearing thresholds gradually increase over time, with the most significant changes observed at lower frequencies and at 3 to 6 months post-treatment. Importantly, hearing loss was found to be dose-dependent, correlating with the maximum cochlear radiation dose (Dmax), and highlighting the critical role of meticulous treatment planning. References 1. Theunissen E, et al. 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