Clinical Characteristics and Outcomes of Tympanomastoid Paragangliomas: A Report from Slovenia.

(1) Background: Head and neck paragangliomas are neuroendocrine tumors that typically originate from the parasympathetic nervous system and are predominantly non-secretory. Their clinical manifestations result from their mass effect on the surrounding tissues. The approach to treating these tumors depends on factors such as their location, size, impact on adjacent structures, and the patient's overall health and preferences. (2) Methods: A retrospective analysis of the management of temporal bone paraganglioma classes A and B (according to the modified Fisch classification) was performed at the University Medical Centre, Ljubljana, between 2011 and 2023. (3) Results: We analyzed 23 cases, 19 of which underwent surgery; complete tumor removal was achieved in 18 of them. Four patients were irradiated due to tumor progression to class C. Three of these four patients initially refused surgery and were treated with radiotherapy (RT) 7, 13, and 18 years after diagnosis. In the fourth patient, complete surgical resection was not achieved and she was treated with RT four years after surgery, due to the growth of the tumor to class C. The average follow-up time from diagnosis was 8.9 years (median 6 years; range 1-26 years). (4) Conclusions: The surgical treatment of patients with class A and B paragangliomas is effective and safe. In cases where surgery is refused but the tumor continues to grow to class C, RT is an alternative and efficient method of controlling tumor growth.

Intravenous lipomas of head and neck: an exceptional entity and its clinical implications.

Intravenous lipomas (IVLs) of the head and neck are uncommon benign tumors that develop within the venous walls, often detected incidentally during imaging for unrelated issues. While usually asymptomatic, these IVLs can cause congestive venous symptoms like swelling, paresthesia or pain in the head and neck and upper limbs, or even venous thromboembolism. The precise diagnosis of IVLs is predominantly achieved through computed tomography (CT) and magnetic resonance imaging (MRI), with CT being the most frequently used method. Symptomatic patients generally undergo open surgery with excision of the IVL followed by venous reconstruction, which has shown safe and effective outcomes. However, the management of asymptomatic IVLs remains controversial due to the limited number of reported cases. Despite this, there is a notable trend toward recommending surgical removal of IVLs to prevent complications and rule out malignancy, driven by the challenges of differentiating IVLs from malignant tumors using imaging alone. This review highlights the key differential imaging characteristics of IVLs and the main surgical techniques to remove the tumor and repair the vascular defect. Further research is necessary to establish a robust, evidence-based approach for treating asymptomatic IVLs, balancing the risks of surgery against the potential for future complications.

Predictive potential of dynamic contrast-enhanced MRI and plasma-derived angiogenic factors for response to concurrent chemoradiotherapy in human papillomavirus-negative oropharyngeal cancer.

BACKGROUND: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can assess tumour vascularity, which depends on the process of angiogenesis and affects tumour response to treatment. Our study explored the associations between DCE-MRI parameters and the expression of plasma angiogenic factors in human papilloma virus (HPV)-negative oropharyngeal cancer, as well as their predictive value for response to concurrent chemoradiotherapy (cCRT). PATIENTS AND METHODS: Twenty-five patients with locally advanced HPV-negative oropharyngeal carcinoma were prospectively enrolled in the study. DCE-MRI and blood plasma sampling were conducted before cCRT, after receiving a radiation dose of 20 Gy, and after the completion of cCRT. Perfusion parameters ktrans, kep, Ve, initial area under the curve (iAUC) and plasma expression levels of angiogenic factors (vascular endothelial growth factor [VEGF], connective tissue growth factor [CTGF], platelet-derived growth factor [PDGF]-AB, angiogenin [ANG], endostatin [END] and thrombospondin-1 [THBS1]) were measured at each time-point. Patients were stratified into responders and non-responders based on clinical evaluation. Differences and correlations between measures were used to generate prognostic models for response prediction. RESULTS: Higher perfusion parameter ktrans and higher plasma VEGF levels successfully discriminated responders from non-responders across all measured time-points, whereas higher iAUC and higher plasma PDGF-AB levels were also discriminative at selected time points. Using early intra-treatment measurements of ktrans and VEGF, a predictive model was created with cut-off values of 0.259 min-1 for ktrans and 62.5 pg/mL for plasma VEGF. CONCLUSIONS: Early intra-treatment DCE-MRI parameter ktrans and plasma VEGF levels may be valuable early predictors of response to cCRT in HPV-negative oropharyngeal cancer.

Psychological Factors Related to Treatment Outcomes in Head and Neck Cancer.

BACKGROUND: Patients with head and neck cancer (HNC) often demonstrate stress, distress, anxiety, depression, and are at risk for suicide. These affect their quality of life (QoL) but less attention has been given to psychological variables that may impact response to treatment. OBJECTIVES: This study aims to systematically review publications during 2013-2023 to collate evidence on the effects of psychological variables on HNC treatment outcomes. METHODS: We searched Ovid Medline, PubMed, Scopus, and Web of Science for articles that examined psychological factors related to treatment outcomes in patients with HNC. RESULTS: There were 29 studies (5 before treatment, 2 during, 17 after, and 5 covering the whole management trajectory) including 362,766 patients. The psychological factors were either behavioral (adjustment and coping strategy, unrealistic ideas, self-blame), cognitive (elevated risk of psychiatric co-comorbidity), or emotional (distress, depression, anxiety, nervousness, and fear of disfigurement and complications). It was found that there was a relationship between depression and decreased survival in patients with HNC. Pretreatment pain was an independent predictor of decreased survival in a large sample of patients. The distress level was approximately  54%, emotional problems ranged between 10 and 44%, while financial difficulties were identified in 54% of the patients. Sixty-nine percent of patients were reported to have used at least one cost-coping strategy within 6 months after treatment initiation. During post-treatment period, depression increased from 15% at the baseline to 29%, while the fear of recurrence was found among at least 35% of patients. DISCUSSION AND CONCLUSION: Several psychological factors predict QoL and survival among HNC survivors. Distress encompasses depression and anxiety, and physical burden from HNC diagnosis and treatment. Routine screening and early interventions that target distress could improve HNC survivors' QoL. A systematic and standardized measurement approach for QoL is warranted to homogenize these findings and to understand the underlying relationships.

Basophil Activation Test Predicts Cetuximab Anaphylaxis Severity in Alpha-Gal IgE-Positive Patients.

Upon first exposure to cetuximab, hypersensitivity reactions can occur. We aimed to assess the utility of the basophil activation test (BAT) to alpha-gal and cetuximab for predicting severe reactions. We prospectively recruited 38 patients and evaluated sIgE to alpha-gal in all patients before the first application of cetuximab. In all alpha-gal-sensitized patients, we evaluated skin tests to meat extracts, gelatine, and cetuximab and performed BAT with alpha-gal and cetuximab. In 24% (9/38) of patients, sIgE to alpha-gal was >0.10 kUA/L, and 8/9 reacted to the cetuximab. Basophil activation tests with alpha-gal were positive in all sensitized patients and were higher in those with severe reactions (18.3% in grade 4 [n = 4] vs. 1.8% in grade 2 [n = 3] or no reaction [n = 1] at 3.3 ng/mL of alpha-gal; p = 0.03). All patients with severe grade 4 reactions had a positive CD63 BAT response to cetuximab compared to patients with moderate or no reaction, who all had negative BAT (57.7% vs. 0.9% at 500 µg/mL, 63.2% vs. 4.1% at 100 µg/mL, 58.2% vs. 2.7% at 10 µg/mL, and 32.1% vs. 3.3% at 1 µg/mL of cetuximab, respectively; p ≤ 0.001). In summary, before initiating cetuximab treatment, sIgE to alpha-gal should be assessed in all patients. To predict the severity of the reaction and to assess the risk of cetuximab-induced anaphylaxis, we should perform BATs with alpha-gal or more discriminative BATs with cetuximab.

HaN-Seg: The head and neck organ-at-risk CT and MR segmentation challenge.

BACKGROUND AND PURPOSE: To promote the development of auto-segmentation methods for head and neck (HaN) radiation treatment (RT) planning that exploit the information of computed tomography (CT) and magnetic resonance (MR) imaging modalities, we organized HaN-Seg: The Head and Neck Organ-at-Risk CT and MR Segmentation Challenge. MATERIALS AND METHODS: The challenge task was to automatically segment 30 organs-at-risk (OARs) of the HaN region in 14 withheld test cases given the availability of 42 publicly available training cases. Each case consisted of one contrast-enhanced CT and one T1-weighted MR image of the HaN region of the same patient, with up to 30 corresponding reference OAR delineation masks. The performance was evaluated in terms of the Dice similarity coefficient (DSC) and 95-percentile Hausdorff distance (HD95), and statistical ranking was applied for each metric by pairwise comparison of the submitted methods using the Wilcoxon signed-rank test. RESULTS: While 23 teams registered for the challenge, only seven submitted their methods for the final phase. The top-performing team achieved a DSC of 76.9 % and a HD95 of 3.5 mm. All participating teams utilized architectures based on U-Net, with the winning team leveraging rigid MR to CT registration combined with network entry-level concatenation of both modalities. CONCLUSION: This challenge simulated a real-world clinical scenario by providing non-registered MR and CT images with varying fields-of-view and voxel sizes. Remarkably, the top-performing teams achieved segmentation performance surpassing the inter-observer agreement on the same dataset. These results set a benchmark for future research on this publicly available dataset and on paired multi-modal image segmentation in general.

Stereotactic Body Radiotherapy in Recurrent and Oligometastatic Head and Neck Tumours.

The treatment of head and neck cancers (HNCs) encompasses a complex paradigm involving a combination of surgery, radiotherapy, and systemic treatment. Locoregional recurrence is a common cause of treatment failure, and few patients are suitable for salvage surgery. Reirradiation with conventional radiation techniques is challenging due to normal tissue tolerance limits and the risk of significant toxicities. Stereotactic body radiotherapy (SBRT) has emerged as a highly conformal modality that offers the potential for cure while limiting the dose to surrounding tissue. There is also growing research that shows that those with oligometastatic disease can benefit from curative intent local ablative therapies such as SBRT. This review will look at published evidence regarding the use of SBRT in locoregional recurrent and oligometastatic HNCs.

Stereotactic Body Radiotherapy as a Curative Treatment for De Novo Mucosal Carcinoma of the Head and Neck: A Feasible Alternative Option for Fragile Patients with Small Lesion: A Systematic Review.

Stereotactic body radiotherapy (SBRT) is characterized by a high dose per fraction, well-defined small targets, superior dose conformity, and a steep off-target dose gradient. A literature search was conducted to examine the experience with SBRT as a curative treatment for newly diagnosed mucosal carcinoma of the head and neck (MCHN). Four retrospective case series and one prospective phase I clinical trial published between 2012 and 2020 described 124 patients. SBRT was mainly performed in older patients with different tumor sites. The median size of the planning target volumes ranged from 5.3 to 41 cm3. Different approaches were used to create margins. In two studies, limited elective nodal irradiation was performed. The equivalent doses used were 60-83.33 Gy delivered in five fractions. Considerable heterogeneity was observed in the radiation dose specification. The incidence of grade ≥3 late toxicity was 0-8.3%, with local and regional control ranging from 73% to 100%. Improved or stable quality of life after SBRT was reported in two studies. Curative-intent SBRT for de novo MCHN appears to be an effective and relatively safe treatment for small tumor targets, preferably without concomitant elective tissue irradiation. Standardization of SBRT practice and well-designed prospective clinical trials are needed to better define the role of SBRT in this setting.

Adaptive radiotherapy for head and neck cancer: Pitfalls and possibilities from the radiation oncologist's point of view.

BACKGROUND: Patients with head and neck cancer (HNC) may experience substantial anatomical changes during the course of radiotherapy treatment. The implementation of adaptive radiotherapy (ART) proves effective in managing the consequent impact on the planned dose distribution. METHODS: This narrative literature review comprehensively discusses the diverse strategies of ART in HNC and the documented dosimetric and clinical advantages associated with these approaches, while also addressing the current challenges for integration of ART into clinical practice. RESULTS AND CONCLUSION: Although based on mainly non-randomized and retrospective trials, there is accumulating evidence that ART has the potential to reduce toxicity and improve quality of life and tumor control in HNC patients treated with RT. However, several questions remain regarding accurate patient selection, the ideal frequency and timing of replanning, and the appropriate way for image registration and dose calculation. Well-designed randomized prospective trials, with a predetermined protocol for both image registration and dose summation, are urgently needed to further investigate the dosimetric and clinical benefits of ART.

Primary Management of Operable Locally Advanced Oral Cavity Squamous Cell Carcinoma: Current Concepts and Strategies.

INTRODUCTION: Locally advanced oral cavity carcinoma (LAOCSCC) is primarily treated with surgery followed by radiotherapy with or without chemotherapy. METHODS: A review of literature using PubMED was performed for studies reporting the management of LAOCSCC. Based on the reviewed literature and opinions of experts in the field, recommendations were made. RESULTS: Studies have shown that outcomes following resection of T4a and infranotch (inferior to mandibular notch) T4b are comparable. We discuss the concept of compartmental resection of LAOCSCC and issues concerning the management of the neck. Further, patients who refuse or are unable to undergo surgery can be treated with chemoradiotherapy with uncertain outcomes. The role of neoadjuvant chemotherapy has shown promise for organ (mandibular) preservation in a select subset of patients. CONCLUSION: The management strategy for LAOCSCC should be determined in a multidisciplinary setting with emphasis on tumor control, functional preservation, and quality of life of the patient.

Neurological complications of modern radiotherapy for head and neck cancer.

Radiotherapy is one of the mainstay treatment modalities for the management of non-metastatic head and neck cancer (HNC). Notable improvements in treatment outcomes have been observed in the recent decades. Modern radiotherapy techniques, such as intensity-modulated radiotherapy and charged particle therapy, have significantly improved tumor target conformity and enabled better preservation of normal structures. However, because of the intricate anatomy of the head and neck region, multiple critical neurological structures such as the brain, brainstem, spinal cord, cranial nerves, nerve plexuses, autonomic pathways, brain vasculature, and neurosensory organs, are variably irradiated during treatment, particularly when tumor targets are in close proximity. Consequently, a diverse spectrum of late neurological sequelae may manifest in HNC survivors. These neurological complications commonly result in irreversible symptoms, impair patients' quality of life, and contribute to a substantial proportion of non-cancer deaths. Although the relationship between radiation dose and toxicity has not been fully elucidated for all complications, appropriate application of dosimetric constraints during radiotherapy planning may reduce their incidence. Vigilant surveillance during the course of survivorship also enables early detection and intervention. This article endeavors to provide a comprehensive review of the various neurological complications of modern radiotherapy for HNC, summarize the current incidence data, discuss methods to minimize their risks during radiotherapy planning, and highlight potential strategies for managing these debilitating toxicities.

Comparison of conventional and hippocampus-sparing radiotherapy in nasopharyngeal carcinoma: In silico study and systematic review.

Background and purpose: Radiation-induced damage to the hippocampi can cause cognitive decline. International recommendations for nasopharyngeal cancer (NPC) radiotherapy (RT) lack specific guidelines for protecting the hippocampi. Our study evaluates if hippocampi-sparing (HS) RT in NPC ensures target coverage and meets recommended dose limits for other at-risk organs. Materials and methods: In a systematic literature review, we compared hippocampal D40% in conventional and HS RT plans. In an in silico dosimetric study, conventional and HS-VMAT plans were created for each patient, following international recommendations for OAR delineation, dose prioritization and acceptance criteria. We assessed the impact on neurocognitive function using a previously published normal tissue complication probability (NTCP) model. Results: In four previous studies (n = 79), researchers reduced D40% hippocampal radiation doses in HS plans compared to conventional RT on average from 24.9 Gy to 12.6 Gy.Among 12 NPC patients included in this in silico study, statistically significant differences between HS and conventional VMAT plans were observed in hippocampal EQD2 Dmax (23.8 vs. 46.4 Gy), Dmin (3.8 vs. 4.6 Gy), Dmean (8.1 vs. 15.1 Gy), and D40% (8.3 vs. 15.8 Gy). PTV coverage and OAR doses were similar, with less homogeneous PTV coverage in HS plans (p = 0.038). This translated to a lower probability of memory decline in HS plans (interquartile range 15.8-29.6 %) compared to conventional plans (33.8-81.1 %) based on the NTCP model (p = 0.002). Conclusion: Sparing the hippocampus in NPC RT is safe and feasible. Given the life expectancy of many NPC patients, their cognitive well-being must be paramount in radiotherapy planning.

vOARiability: Interobserver and intermodality variability analysis in OAR contouring from head and neck CT and MR images.

BACKGROUND: Accurate and consistent contouring of organs-at-risk (OARs) from medical images is a key step of radiotherapy (RT) cancer treatment planning. Most contouring approaches rely on computed tomography (CT) images, but the integration of complementary magnetic resonance (MR) modality is highly recommended, especially from the perspective of OAR contouring, synthetic CT and MR image generation for MR-only RT, and MR-guided RT. Although MR has been recognized as valuable for contouring OARs in the head and neck (HaN) region, the accuracy and consistency of the resulting contours have not been yet objectively evaluated. PURPOSE: To analyze the interobserver and intermodality variability in contouring OARs in the HaN region, performed by observers with different level of experience from CT and MR images of the same patients. METHODS: In the final cohort of 27 CT and MR images of the same patients, contours of up to 31 OARs were obtained by a radiation oncology resident (junior observer, JO) and a board-certified radiation oncologist (senior observer, SO). The resulting contours were then evaluated in terms of interobserver variability, characterized as the agreement among different observers (JO and SO) when contouring OARs in a selected modality (CT or MR), and intermodality variability, characterized as the agreement among different modalities (CT and MR) when OARs were contoured by a selected observer (JO or SO), both by the Dice coefficient (DC) and 95-percentile Hausdorff distance (HD 95 $_{95}$ ). RESULTS: The mean (±standard deviation) interobserver variability was 69.0 ± 20.2% and 5.1 ± 4.1 mm, while the mean intermodality variability was 61.6 ± 19.0% and 6.1 ± 4.3 mm in terms of DC and HD 95 $_{95}$ , respectively, across all OARs. Statistically significant differences were only found for specific OARs. The performed MR to CT image registration resulted in a mean target registration error of 1.7 ± 0.5 mm, which was considered as valid for the analysis of intermodality variability. CONCLUSIONS: The contouring variability was, in general, similar for both image modalities, and experience did not considerably affect the contouring performance. However, the results indicate that an OAR is difficult to contour regardless of whether it is contoured in the CT or MR image, and that observer experience may be an important factor for OARs that are deemed difficult to contour. Several of the differences in the resulting variability can be also attributed to adherence to guidelines, especially for OARs with poor visibility or without distinctive boundaries in either CT or MR images. Although considerable contouring differences were observed for specific OARs, it can be concluded that almost all OARs can be contoured with a similar degree of variability in either the CT or MR modality, which works in favor of MR images from the perspective of MR-only and MR-guided RT.

Association of a gene-expression subtype to outcome and treatment response in patients with recurrent/metastatic head and neck squamous cell carcinoma treated with nivolumab.

BACKGROUND: Immune checkpoint inhibitors have been approved and currently used in the clinical management of recurrent and metastatic head and neck squamous cell carcinoma (R/M HNSCC) patients. The reported benefit in clinical trials is variable and heterogeneous. Our study aims at exploring and comparing the predictive role of gene-expression signatures with classical biomarkers for immunotherapy-treated R/M HNSCC patients in a multicentric phase IIIb trial. METHODS: Clinical data were prospectively collected in Nivactor tiral (single-arm, open-label, multicenter, phase IIIb clinical trial in platinum-refractory HNSCC treated with nivolumab). Findings were validated in an external independent cohort of immune-treated HNSCC patients, divided in long-term and short-term survivors (overall survival >18 and <6 months since the start of immunotherapy, respectively). Pretreatment tumor tissue specimen from immunotherapy-treated R/M HNSCC patients was used for PD-L1 (Tumor Proportion Score; Combined Positive Score (CPS)) and Tumor Mutational Burden (Oncopanel TSO500) evaluation and gene expression profiling; classical biomarkers and immune signatures (retrieved from literature) were challenged in the NIVACTOR dataset. RESULTS: Cluster-6 (Cl6) stratification of NIVACTOR cases in high score (n=16, 20%) and low score (n=64, 80%) demonstrated a statistically significant and clinically meaningful improvement in overall survival in the high-score cases (p=0.00028; HR=4.34, 95% CI 1.84 to 10.22) and discriminative ability reached area under the curve (AUC)=0.785 (95% CI 0.603 to 0.967). The association of high-score Cl6 with better outcome was also confirmed in: (1) NIVACTOR progression-free survival (p=4.93E-05; HR=3.71, 95% CI 1.92 to 7.18) and objective-response-rate (AUC=0.785; 95% CI 0.603 to 0.967); (2) long survivors versus short survivors (p=0.00544). In multivariate Cox regression analysis, Cl6 was independent from Eastern Cooperative Oncology Group performance status, PDL1-CPS, and primary tumor site. CONCLUSIONS: These data highlight the presence of underlying biological differences able to predict survival and response following treatment with immunotherapy in platinum-refractory R/M HNSCC that could have translational implications improving treatment selection. TRIAL REGISTRATION NUMBER: EudraCT Number: 2017-000562-30.

Post-radiation xerostomia therapy with allogeneic mesenchymal stromal stem cells in patients with head and neck cancer: study protocol for phase I clinical trial.

BACKGROUND: Xerostomia is a common side effect of radiotherapy in patients with head and neck tumors that negatively affects quality of life. There is no known effective standard treatment for xerostomia. Here, we present the study protocol used to evaluate the safety and preliminary efficacy of allogeneic mesenchymal stromal stem cells (MSCs) derived from umbilical cord tissue. PATIENTS AND METHODS: Ten oropharyngeal cancer patients with post-radiation xerostomia and no evidence of disease recurrence 2 or more years after (chemo)irradiation (intervention group) and 10 healthy volunteers (control group) will be enrolled in this nonrandomized, open-label, phase I exploratory study. MSCs from umbilical cord tissue will be inserted under ultrasound guidance into both parotid glands and both submandibular glands of the patients. Toxicity of the procedure will be assessed according to CTCAE v5.0 criteria at days 0, 1, 5, 28, and 120. Efficacy will be assessed by measuring salivary flow and analyzing its composition, scintigraphic evaluation of MSC grafting, retention, and migration, and questionnaires measuring subjective xerostomia and quality of life. In addition, the radiological, functional, and morphological characteristics of the salivary tissue will be assessed before, at 4 weeks, and at 4 months after the procedure. In the control group subjects, only salivary flow rate and salivary composition will be determined. DISCUSSION: The use of allogeneic MSCs from umbilical cord tissue represents an innovative approach for the treatment of xerostomia after radiation. Due to the noninvasive collection procedure, flexibility of cryobanking, and biological advantages, xerostomia therapy using allogeneic MSCs from umbilical cord tissue may have an advantage over other similar therapies.

Review of Outcomes after Salvage Surgery for Recurrent Squamous Cell Carcinoma of the Head and Neck.

Surgery with adjuvant chemoradiotherapy or chemoradiotherapy is the mainstay in treatment for advanced stage head and neck squamous cell carcinoma; however, locoregional recurrences are frequent. Salvage surgery could be proposed in selected patients to improve local control, disease-free, and overall survival. Factors for improved disease-free and overall survival in patients treated with salvage surgery include age, tumor location, the initial T stage, HPV status, resection margins, and the time elapsing from the initial treatment. Clinical trials with adjuvant therapies have shown promise after salvage surgery in terms of tolerance and response, but clinical guidelines for using these adjuvant treatments are currently lacking. The aim of this review is to present current knowledge concerning the incidence and management of recurrent head and neck squamous cell carcinoma and current data concerning survival and morbidity after salvage surgery.

Progress and emerging strategies to preserve function in the treatment of sinonasal cancer.

The sinonasal structures and their adjacent organs host several functions including vision, olfaction, nasal respiration and filtration, secretory immunity, facial expression, articulation, and oral deglutition. We reviewed the current evidence supporting functional preservation in sinonasal cancer treatment. Primary surgery with or without adjuvant modalities continues to be the standard of care for sinonasal cancer. Unfortunately, functional compromise remains a dominant negative feature of this approach. More recently, through advances in therapeutic techniques and improved understanding of the relevant tumor biology, treatments aimed at preserving function and cosmesis are emerging. The evidence for such progress involving minimal access surgery, surgical reconstruction for rehabilitation, new techniques in radiation therapy, inclusion of systemic and locally enhanced chemotherapy, and therapeutic agents based on molecular targets are highlighted. This multi-prong approach bodes well for future patients with sinonasal cancer to undergo successful treatment that includes maximal preservation of associated functions.

Survival Outcomes in T3 Laryngeal Cancers: Primary Total Laryngectomy vs. Concurrent Chemoradiation or Radiation Therapy-A Meta-Analysis.

BACKGROUND: The management of cT3 laryngeal cancers remains controversial, with studies recommending surgical or non-surgical approaches. Despite the many papers that have been published on the subject, there is a lack of studies showing which treatment has better results in terms of survival. OBJECTIVE: To determine the difference in survival outcomes following total laryngectomy (TL), concurrent chemoradiation (CRT) or radiation therapy (RT) alone in T3 laryngeal cancers. METHODS: Search of PubMed, Scopus, and Google Scholar databases from 1995 to 2023 employing specific keywords and Boolean operators to retrieve relevant articles. Statistical analysis was conducted using a random-effects model, and heterogeneity was evaluated using the Q-test and I2 statistic. Funnel plot asymmetry was assessed using rank correlation and regression tests. RESULTS: The qualitative data synthesis comprised 10,940 patients from 16 included studies. TL was performed in 2149 (19.4%), CRT in 6723 (61.5%), RT in 295 (2.7%), while non-surgical treatment was not specified in 1773 (16.2%) patients. The pooled 2-year overall survival (OS) rates were TL = 73%, CRT = 74.7%, RT = 57.9%, 3-year OS rates were TL = 64.3%, CRT = 62.9%, RT = 52.4%, and 5-year OS rates were TL = 54.2%, CRT = 52.7%, RT = 40.8%. There was a significant heterogeneity in the included studies. There was no statistically significant difference in 2-year OS (logOR= -0.88 (95% confidence interval (CI): -1.99 to 0.23), p = 0.12), 3-year OS (logOR = -0.6 (95% CI: -1.34 to 0.15), p = 0.11), and 5-year OS (logOR = -0.54 (95% CI: -1.29 to 0.21), p = 0.16) between TL and CRT. Instead, there was significant difference in 2-year OS (logOR= -1.2383 (95% CI: -2.1679 to -0.3087), p = 0.009), 3-year OS (-1.1262 (95% CI: -1.6166 to -0.6358), p < 0.001), and 5-year OS (-0.99 (95% CI: -1.44 to -0.53)), p < 0.001) between TL and RT alone. CONCLUSIONS AND SIGNIFICANCE: TL followed with adjuvant (chemo)radiation on indication and CRT with salvage surgery in reserve appear to have similar OS outcomes. Both resulted in better OS outcomes compared to RT alone in the treatment of T3 laryngeal cancers. If patients are unfit for chemotherapy, making CRT impossible, surgery may become the choice of treatment.