Background: Cisplatin, a widely used chemotherapeutic agent, is associated with significant ototoxicity, leading to progressive and irreversible sensorineural hearing loss in up to 93% of patients. Cisplatin generates reactive oxygen species (ROS) in the cochlea, activating apoptotic and necroptotic pathways that result in hair cell death. Inflammatory processes and nitrative stress also contribute to cochlear damage. Methods: This literature review was conducted to explore the mechanisms underlying cisplatin-induced ototoxicity and evaluate protective strategies, including both current and emerging approaches. A structured search was performed in multiple scientific databases, including PubMed and ScienceDirect, for articles published up to November 2024. Results: Current otoprotective strategies include systemic interventions such as antioxidants, anti-inflammatory agents, and apoptosis inhibitors, as well as localized delivery methods like intratympanic injection and nanoparticle-based systems. However, these approaches have limitations, including potential interference with cisplatin’s antitumor efficacy and systemic side effects. Emerging strategies focus on genetic and biomarker-based risk stratification, novel otoprotective agents targeting alternative pathways, and combination therapies. Repurposed drugs like pravastatin also show promise in reducing cisplatin-induced ototoxicity. Conclusions: Despite these advancements, significant research gaps remain in translating preclinical findings to clinical applications and developing selective otoprotective agents that do not compromise cisplatin’s efficacy. This review examines the mechanisms of cisplatin-induced ototoxicity, current otoprotective strategies, and emerging approaches to mitigate this adverse effect.

Otorhinolaryngological (ORL) cancers, including malignancies of the oral cavity, pharynx, and larynx, show significant challenges in oncology. Cisplatin, a platinum-based chemotherapy drug, remains a cornerstone of treatment but is often limited by systemic toxicity and resistance. A comprehensive literature review was conducted using recent studies and clinical trials focused on nanotechnology-based cisplatin delivery systems. The analysis covered various types of nanocarriers, their mechanisms, and advantages. Additionally, the limitations of nanotechnology-based cisplatin delivery systems were discussed. Findings indicate that lipid-based nanoparticles, polymeric nanoparticles, inorganic nanoparticles, and extracellular vesicles have demonstrated improved drug targeting, bioavailability, and reduced systemic toxicity in preclinical and clinical studies. Nanocarriers also offer potential for overcoming drug resistance and enabling combination therapy. However, challenges related to biocompatibility, scalability, and regulatory approval remain significant barriers to widespread clinical adoption. Nanotechnology offers a novel and promising approach to optimizing cisplatin delivery for ORL cancers. While preclinical studies demonstrate significant potential, further research and clinical validation are essential to translate these advancements into routine clinical practice. Addressing manufacturing and regulatory challenges will be critical for future research.

Background/Objectives: Hearing impairment is a frequent but under-recognized sequela of (chemo)radiotherapy for head and neck cancer (HNC). We assessed the frequency of early post-treatment hearing changes and their association with cochlear radiation exposure and concurrent platinum-based chemotherapy. Methods: We conducted a single-center retrospective cohort study of 70 consecutive patients with HNC treated with radiotherapy between November 2024 and September 2025. Patients receiving concurrent chemoradiotherapy (CRT, n = 48) were compared with patients receiving radiotherapy alone (RT, n = 22). The primary outcome was clinically documented post-treatment hearing change. Cochlear maximum point doses (Dmax) were extracted from treatment plans. Analyses included Fisher exact and Mann–Whitney U tests, Spearman correlations, Firth penalized logistic regression, a Cochran–Armitage trend test, and restricted cubic splines. Results: Post-treatment hearing changes were documented in 38/70 patients (54.3%): 58.3% after CRT versus 45.5% after RT alone (odds ratio (OR) 1.68, 95% confidence interval (CI) 0.61–4.49, p = 0.439). Mean cochlear Dmax was higher in patients with hearing change (median 5.5 vs. 2.5 Gy, p = 0.045) and correlated with the outcome (ρ = 0.244, p = 0.043), with hearing-change rates of 34.8%, 65.2%, and 65.2% across cochlear-dose tertiles (trend p = 0.038). In Firth regression adjusted for age, pre-treatment hearing loss, and concurrent CRT, the association was attenuated and not statistically significant (adjusted OR 1.31 per 10 Gy, 95% CI 0.82–2.08, p = 0.253), and it was attenuated further after accounting for tumor site (OR 1.09 per 10 Gy, 95% CI 0.66–1.80, p = 0.735), with oropharyngeal primary the strongest correlate of hearing change (OR 4.02, 95% CI 1.28–12.6). Paired audiograms were available in only 10 patients, seven of whom showed audiometric deterioration; a conductive component could not be excluded in 14/38 events. No patient exceeded the QUANTEC mean cochlear-dose constraint of 45 Gy. Conclusions: Early, clinically apparent hearing changes affected more than half of this contemporary cohort. The univariable association with cochlear dose did not persist after adjustment, particularly for tumor site, and the available audiometric data do not allow hearing changes to be attributed specifically to cochlear injury. These findings underscore the need for systematic baseline and follow-up audiometry rather than demonstrating that further cochlear-dose reduction would improve hearing outcomes.

Background and Objectives: Laryngeal cancer imposes substantial inpatient costs in middle-income health systems. We described recent trends in laryngeal cancer hospitalizations in Romania, estimated hospital expenditure, and modeled the impact of prevention scenarios to 2035. Methods: We conducted an ecological analysis of 20,056 discharges diagnosed as laryngeal cancer (ICD-10 C32.x) between 2019 and 2023. Each episode was assigned a mean unit cost of 1100 USD, with age- and residence-specific adjustments, and re-priced using EU (3900 USD) and US (30,000 USD) tariffs. We derived annual costs and projected 2035 expenditure under three prevention scenarios. Results: Annual discharges fell from 5408 in 2019 to 3151–3212 in 2020–2021, then rose to 4409 in 2023, while inpatient spending ranged from 3.47 to 5.95 million USD, reaching 4.85 million USD in 2023 (22,200 USD/100,000 population). Re-pricing 2023 activity at EU and US unit costs yielded counterfactual totals of 17.20 and 132.27 million USD. Older adults (≥65 years) generated 47.6% of discharges and 49.1% of spending in 2023, and urban residence increased the odds of age ≥65 by 48% (OR 1.48, 95% CI 1.40–1.57). Without new prevention, costs are projected to reach 12.60 million USD by 2035; a 30% smoking reduction and a combined package including radon mitigation and dysphonia screening would lower 2035 costs to 10.33 and 9.07 million USD. Conclusions: Demographic aging and sustained case volume will markedly increase hospital costs, while prevention scenarios are associated with lower projected inpatient expenditure.

Background/Objectives: Management of locally advanced cervical cancer (LACC) and other gynecological malignancies aims to achieve locoregional control while avoiding morbid surgical salvage. This exploratory, hypothesis-generating study described the treatment pathways of three protocol groups and examined whether clinical, sociodemographic, and treatment-deviation variables are associated with any oncological surgery. Methods: Sixty-nine adult patients with gynecological or urogenital cancers (89.9% cervical carcinoma) treated with platinum-based chemotherapy at a Romanian tertiary center between April 2024 and April 2025 were stratified into INTERLACE-type dose-dense induction chemotherapy followed by chemoradiotherapy (Group A, n = 27), classic three-weekly neoadjuvant chemotherapy followed by chemoradiotherapy (Group B, n = 7), and no induction chemotherapy (Group C, n = 35). Associations with any oncological surgery (upfront, completion, or salvage) were explored by multivariable logistic regression with bootstrap internal validation, Firth penalized regression, and restricted sensitivity analyses. Results: Twenty-five patients (36.2%) underwent surgery (14 upfront, 8 completion, 3 salvage), and none of them were from Group A, whose median follow-up was only 8.6 months and whose allocation was confounded by diagnosis and stage. The model showed an apparent area under the curve of 0.717 (optimism-corrected 0.672), accuracy of 73.9% against a no-information rate of 63.8% (p = 0.049), sensitivity of 0.480, and specificity of 0.886. Urban provenience (OR 0.343, 95% CI 0.113–1.039, p = 0.059), Delta Target Dose (OR 1.109 per Gy, p = 0.076), and number of chemotherapy cycles (OR 1.298 per cycle, p = 0.076) showed non-significant trends whose direction was unchanged in all sensitivity analyses. Conclusions: The absence of surgery after induction chemotherapy is hypothesis-generating rather than confirmatory, and the exploratory model is not a clinical prediction tool. Geographic provenience and planning-to-delivery treatment deviation are candidate variables for prospective evaluation in a homogeneous LACC population with standardized radiotherapy parameters and mature oncological endpoints.

Background and Objectives: Audiometric monitoring is recommended for patients receiving ototoxic (chemo)radiotherapy for head and neck cancer (HNC), yet real-world uptake is poorly characterized and potentially inequitable. We quantified the uptake and timing of audiometric testing and examined rural–urban residence and age as candidate determinants. Materials and Methods: We conducted a single-center retrospective cohort study of 70 consecutive patients with HNC treated with radiotherapy between November 2024 and September 2025, comparing rural (n = 32) and urban (n = 38) residents. Outcomes were audiometric testing at treatment initiation, repeat audiometry during follow-up, and post-treatment hearing change. Analyses included Fisher’s exact and Mann–Whitney U tests, Spearman correlations, Firth-penalized logistic regression, inverse probability of treatment weighting (IPTW), restricted cubic splines, and sensitivity analyses. Results: Audiometry at treatment initiation was performed in 31/70 patients (44.3%) and repeat audiometry in only 10/70 (14.3%); among tested patients with documented dates, just 19.4% underwent audiometry before the first radiotherapy fraction, so that a true pre-exposure baseline existed for only 6/70 patients (8.6%). Uptake at initiation was 53.7% with concurrent cisplatin, 14.3% with carboplatin, and 36.4% with radiotherapy alone (p = 0.114). Uptake did not differ by residence (rural 40.6% vs. urban 47.4%; odds ratio (OR) 0.76, 95% confidence interval (CI) 0.30–1.96, p = 0.634), with an IPTW-weighted risk difference of −9.9% (95% CI −30.9 to +11.8). Age was the dominant determinant: uptake fell from 90.5% below 65 years to 24.5% at ≥65 years (adjusted OR per decade 0.32, 95% CI 0.15–0.71, p = 0.005), with significant non-linearity (p = 0.015). Pre-existing hearing loss was associated with lower testing (OR 0.29, 95% CI 0.10–0.91, p = 0.032). Post-treatment hearing change occurred in 54.3% overall (rural 46.9% vs. urban 60.5%, p = 0.336), comprising a subjective hearing complaint in 51.4% and audiometric deterioration in six of the nine patients with paired audiograms. Conclusions: Audiometric monitoring was incomplete, rarely obtained before irradiation, and steeply age-patterned, whereas rural residence was not associated with lower uptake; structured, exposure-based referral pathways, triggered by planned cisplatin and clinically relevant cochlear dose and applied irrespective of age, are warranted.