Kristine Guran

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: 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.

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.

Exosome-derived microRNAs (miRNAs) have been proposed as minimally invasive biomarkers for laryngeal squamous- cell carcinoma (LSCC). Because oral and maxillofacial surgeons are integral to head-and-neck oncologic and reconstructive pathways, such liquid-biopsy signals could support perioperative decision-making (selection for organ-preserving surgery), margin surveillance, and reconstructive planning. We conducted a preregistered, protocol-driven search of PubMed/MEDLINE, Web of Science, and Scopus from inception to 1 June 2025. Given the very small number of clinically comparable diagnostic studies, discordant index tests/thresholds, and high heterogeneity, we did not perform quantitative pooling or publication-bias testing. Instead, we undertook a narrative synthesis and constructed an evidence map; risk of bias tools (QUADAS-2; ROBINS-I) were applied descriptively to inform qualitative confidence. Nine studies were formally analysed based on eligibility to the study topic. Two serum-based case–control investigations (111 LSCC, 80 controls) reported areas under the ROC curve of 0.876 (miR-21 + HOTAIR) and 0.797 (miR-941), with corresponding sensitivities of 94% and 82%. Seven mechanistic papers showed that vesicular cargos—including miR-1246, circPVT1, and LINC02191—drive STAT3-dependent M2 polarisation, NOTCH1-mediated stemness, Rap1b-VEGFR2 angiogenesis, and glycolytic re-programming, producing 1.6–2.6-fold increases in invasion, tube formation, or xenograft growth. Only three studies fulfilled MISEV-2018 characterisation criteria, and none incorporated external validation. This narrative review and evidence map identifies promising but preliminary diagnostic signals and biologically plausible mechanisms for exosomal miRNAs in LSCC; however, the evidence is sparse, single-region, methodologically inconsistent, and at high risk of bias. Findings do not support clinical implementation at this stage. Priorities include harmonised EV workflows, prespecified thresholds, and prospective, multi-centre validation.

Background and Objectives: Laryngeal cancer imposes a disproportionate burden on speech, airway protection and long-term quality of life. Contemporary population-based data for Central and Eastern Europe remain scarce, and the post-pandemic trajectory is uncertain. Materials and Methods: We performed a nationwide, retrospective ecological time-series study using Romanian mortality registers and hospital-discharge files for 2017–2023. Crude and age-standardised mortality rates (ASMRs) were calculated, county-level indirect standardisation and spatial autocorrelation assessed and joinpoint regression quantified temporal trends. Forecasts to 2040 combined Holt–Winters/ARIMA models with Elliott-wave heuristics anchored to Fibonacci retracements. Results: In 2023, 798 laryngeal cancer deaths yielded a crude mortality of 3.65/100,000 (95% CI 3.41–3.91). Male mortality (7.07/100,000) exceeded female mortality 18-fold. Rural residents experienced a higher rate than urban counterparts (4.26 vs. 3.04/100,000), a difference unchanged after indirect age standardisation. National ASMR fell by 3.7% annually (p < 0.01), yet five counties formed a high-risk corridor (standardised mortality ratios 1.59–1.82); Moran’s I = 0.27 (p < 0.01) indicated significant spatial clustering. Pandemic-era surgical throughput collapsed by 48%, generating a backlog projected to persist beyond 2030. Ensemble forecasting anticipates a doubling of discharges and mortality between 2034 and 2037 unless smoking prevalence falls by ≥30% and radon exposure is curtailed. Conclusions: Although overall laryngeal cancer mortality in Romania is declining, the pace lags behind Western Europe and is threatened by geographic inequities and pandemic-related care delays. Aggressive tobacco control, radon-remediation policies and expansion of surgical and radiotherapeutic capacity are required to avert a forecasted surge in the next decade.

Background and Objectives: Vitamin D deficiency and psychological distress have been linked to cancer biology, but their relevance to tumor differentiation in head-and-neck squamous cell carcinoma (HNSCC) is uncertain. Materials and Methods: In this cross-sectional study at the Department of Otolaryngology, County Hospital of Timișoara, Romania, we enrolled newly diagnosed HNC patients from October 2023 to December 2024, analyzing 199 SCC patients after exclusions. Vitamin D status was assessed using serum 25-OH-vitamin D levels, and distress was measured with the validated Romanian version of the Hospital Anxiety and Depression Scale (HADS). Tumor aggressiveness was defined by histological grade (G3 vs. G1–G2). Univariate, multivariate, and subgroup analyses were conducted, adjusting for confounders like smoking. Results: Vitamin D deficiency (p = 0.055) and between clinically significant anxiety (HADS-A ≥ 8) and G3 tumors (OR = 1.71, p = 0.059). A weak negative correlation was observed between 25-OH-vitamin D levels and HADS-A scores (rho = −0.17, p = 0.052). In multivariate analysis adjusted for age, smoking, and tumor location, these associations weakened (vitamin D deficiency: OR = 1.55, p = 0.082; HADS-A ≥8: OR = 1.56, p = 0.113). Subgroup analysis suggested a trend toward higher odds of G3 tumors in patients with both vitamin D deficiency and high anxiety (OR = 1.72, p = 0.075). Conclusions: Univariate analyses indicated potential links between vitamin D deficiency, psychological distress, and tumor aggressiveness in HNSCC, but these did not reach statistical significance after adjustment for confounders. The observed trends, particularly in subgroups with combined deficiency and distress, suggest a possible interplay worth exploring further. To conclude, neither vitamin-D deficiency nor clinically significant distress independently predicted poor histological differentiation after adjustment; observed trends, including a possible distress–vitamin-D interaction, are hypothesis-generating and warrant testing in larger, longitudinal cohorts.

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 and Objectives: Despite notable advances in diagnosing and managing laryngeal cancer, the disease continues to present challenges, particularly in the advanced stages. Circulating microRNAs (miRNAs) are increasingly recognized as accessible biomarkers for cancer detection and follow-up. This exploratory study centers on identifying and evaluating miRNAs that are specifically downregulated in laryngeal carcinoma patients, aiming to clarify their clinical relevance in distinguishing pre- and post-therapeutic states. Methods: A total of 30 patients with laryngeal cancer provided paired blood samples before and after undergoing surgical or non-surgical treatment. To reduce variability and resource demand, each set of 10 samples was pooled into three pre-treatment groups (P1, P2, and P3) and three corresponding post-treatment groups (C1, C2, and C3). Total RNA, including miRNAs, was isolated from both plasma and exosomes, followed by qPCR-based profiling (Qiagen platform). Downregulated miRNAs were singled out through statistical comparisons using Mann–Whitney U tests; receiver operating characteristic (ROC) analyses and logistic regression were further applied to assess diagnostic utility. Results: Seven miRNAs demonstrated significant downregulation in the pre-treatment samples (fold changes ranging from 0.20 to 0.64, p < 0.05). Notably, hsa-miR-107 and hsa-let-7a-5p both showed marked reductions of approximately fivefold (p < 0.01), suggesting a strong association with active tumor presence. In ROC analysis, hsa-miR-107 achieved an area under the curve (AUC) of 0.78 (95% CI: 0.62–0.90) with 72% sensitivity and 74% specificity in differentiating pre- from post-treatment states. A logistic regression model incorporating downregulated candidates produced odds ratios between 0.52 and 0.64 (p < 0.05), pointing to their potential additive value in clinical decision-making. Conclusions: These preliminary findings indicate that certain miRNAs, when suppressed in circulation, may be linked to the oncogenic milieu of laryngeal cancer. Confirming these observations in larger, multicenter investigations is critical, but this pilot work underscores the promise of downregulated miRNAs as biomarkers of disease activity and potential guides to therapy response.

Background and Objectives: Laryngeal cancer poses a significant clinical challenge, with late-stage diagnosis contributing to high morbidity and mortality. Circulating microRNAs (miRNAs) represent promising, minimally invasive biomarkers for earlier detection and improved therapeutic monitoring. This pilot study focused exclusively on miRNAs found to be upregulated in laryngeal carcinoma patients, aiming to elucidate their diagnostic and prognostic relevance. Methods: A total of 50 participants meeting standardized inclusion criteria were recruited from the ENT Clinic in Timișoara. Of these, 30 patients provided paired blood samples before and after treatment (surgical or non-surgical). Samples were pooled into three preoperative groups (P1, P2, P3) and three corresponding postoperative groups (C1, C2, C3). miRNAs were extracted from plasma and exosomes, and relative expression was measured by qPCR (Qiagen platform). Statistical analyses included Mann–Whitney U tests, receiver operating characteristic (ROC) curves, and logistic regression. Results: Seven miRNAs consistently exhibited significant upregulation preoperatively. Notably, hsa-miR-424-5p displayed a mean fold change of 4.59 (p = 0.0091) relative to postoperative samples, while hsa-miR-186-5p increased by 2.19-fold (p = 0.0030). hsa-miR-15b-5p also showed a substantial preoperative upregulation of 1.77-fold (p = 0.0057). In ROC analyses, hsa-miR-424-5p yielded an area under the curve (AUC) of 0.82 (95% CI 0.70–0.94), with 78% sensitivity and 80% specificity in distinguishing preoperative from postoperative status. Logistic regression indicated that elevated levels of hsa-miR-424-5p (OR = 1.56, 95% CI 1.10–2.20) and hsa-miR-186-5p (OR = 1.32, 95% CI 1.02–1.68) significantly predicted the preoperative disease state. Conclusions: These data underscore the potential of upregulated circulating miRNAs to serve as biomarkers for active laryngeal cancer and to monitor treatment response. Although preliminary, the findings encourage further research with larger cohorts and additional endpoints. With thorough validation, upregulated miRNAs could be integrated into clinical workflows, enhancing diagnostic precision, risk stratification, and postoperative surveillance in laryngeal cancer.

Melissa officinalis is a medicinal herb with an extensive pharmacological profile that has been proven to have beneficial effects in oral and gastrointestinal disorders. However, the effects of this plant in oral, pharyngeal, and colorectal malignancies, types of cancer with an increased incidence in recent years, are less investigated. The present study aims to evaluate the pharmacological profile of a Melissa officinalis total extract for potential benefits in oral, pharynx and colorectal carcinoma. The LC-MS profile of MO total extract (MOte) indicated a rich content in polyphenols, data that support the potent antioxidant capacity exhibited and the antimicrobial activity against both Gram-negative and Gram-positive bacteria. In addition, MOte triggered a dose-dependent and selective decrease in the viability of tumor cells (tongue and pharynx squamous cell carcinomas, and colorectal adenocarcinoma), with the most significant effect being recorded at 100 μg/mL. At the same concentration, MOte exhibited an antiangiogenic effect by inhibiting the process of angiogenesis in ovo. Overall, our findings support the potential benefits of Melissa officinalis leaf total extract as a valuable candidate for the prophylaxis of oral, pharyngeal and colorectal neoplasms.