Mitochondrial outer membrane protein MTUS1/ATIP1 exerts antitumor effects through ROS-induced mitochondrial pyroptosis in head and neck squamous cell carcinoma.

We showed that microtubule-associated tumor suppressor gene (MTUS1/ATIP) downregulation correlated with poor survival in head and neck squamous cell carcinoma (HNSCC) patients and that MTUS1/ATIP1 was the most abundant isoform in HNSCC tissue. However, the location and function of MTUS1/ATIP1 have remain unclear. In this study, we confirmed that MTUS1/ATIP1 inhibited proliferation, growth and metastasis in HNSCC in cell- and patient-derived xenograft models in vitro and in vivo. MTUS1/ATIP1 localized in the outer mitochondrial membrane, influence the morphology, movement and metabolism of mitochondria and stimulated oxidative stress in HNSCC cells by directly interacting with MFN2. MTUS1/ATIP1 activated ROS, recruiting Bax to mitochondria, facilitating cytochrome c release to the cytosol to activate caspase-3, and inducing GSDME-dependent pyroptotic death in HNSCC cells. Our findings showed that MTUS1/ATIP1 localized in the outer mitochondrial membrane in HNSCC cells and mediated anticancer effects through ROS-induced pyroptosis, which may provide a novel therapeutic strategy for HNSCC treatment.

m1A inhibition fuels oncolytic virus-elicited antitumor immunity via downregulating MYC/PD-L1 signaling.

N1-methyladenosine (m1A) RNA methylation is critical for regulating mRNA translation; however, its role in the development, progression, and immunotherapy response of head and neck squamous cell carcinoma (HNSCC) remains largely unknown. Using Tgfbr1 and Pten conditional knockout (2cKO) mice, we found the neoplastic transformation of oral mucosa was accompanied by increased m1A modification levels. Analysis of m1A-associated genes identified TRMT61A as a key m1A writer linked to cancer progression and poor prognosis. Mechanistically, TRMT61A-mediated tRNA-m1A modification promotes MYC protein synthesis, upregulating programmed death-ligand 1 (PD-L1) expression. Moreover, m1A modification levels were also elevated in tumors treated with oncolytic herpes simplex virus (oHSV), contributing to reactive PD-L1 upregulation. Therapeutic m1A inhibition sustained oHSV-induced antitumor immunity and reduced tumor growth, representing a promising strategy to alleviate resistance. These findings indicate that m1A inhibition can prevent immune escape after oHSV therapy by reducing PD-L1 expression, providing a mutually reinforcing combination immunotherapy approach.

CHMP2A regulates broad immune cell-mediated antitumor activity in an immunocompetent in vivo head and neck squamous cell carcinoma model.

BACKGROUND: Natural killer (NK) cells are key effector cells of antitumor immunity. However, tumors can acquire resistance programs to escape NK cell-mediated immunosurveillance. Identifying mechanisms that mediate this resistance enables us to define approaches to improve immune-mediate antitumor activity. In previous studies from our group, a genome-wide CRISPR-Cas9 screen identified Charged Multivesicular Body Protein 2A (CHMP2A) as a novel mechanism that mediates tumor intrinsic resistance to NK cell activity. METHODS: Here, we use an immunocompetent mouse model to demonstrate that CHMP2A serves as a targetable regulator of not only NK cell-mediated immunity but also other immune cell populations. Using the recently characterized murine 4MOSC model system, a syngeneic, tobacco-signature murine head and neck squamous cell carcinoma model, we deleted mCHMP2A using CRISPR/Cas9-mediated knock-out (KO), following orthotopic transplantation into immunocompetent hosts. RESULTS: We found that mCHMP2A KO in 4MOSC1 cells leads to more potent NK-mediated tumor cell killing in vitro in these tumor cells. Moreover, following orthotopic transplantation, KO of mCHMP2A in 4MOSC1 cells, but not the more immune-resistant 4MOSC2 cells enables both T cells and NK cells to better mediate antitumor activity compared with wild type (WT) tumors. However, there was no difference in tumor development between WT and mCHMP2A KO 4MOSC1 or 4MOSC2 tumors when implanted in immunodeficient mice. Mechanistically, we find that mCHMP2A KO 4MOSC1 tumors transplanted into the immunocompetent mice had significantly increased CD4+T cells, CD8+T cells. NK cell, as well as fewer myeloid-derived suppressor cells (MDSC). CONCLUSIONS: Together, these studies demonstrate that CHMP2A is a targetable inhibitor of cellular antitumor immunity.

Comparative analysis of the tumor microbiome, molecular profiles, and immune cell abundances by HPV status in mucosal head and neck cancers and their impact on survival.

Head and Neck Squamous Cell Carcinoma (HNSCC) comprises a diverse group of tumors with variable treatment response and prognosis. The tumor microenvironment (TME), which includes microbiome and immune cells, can impact outcomes. Here, we sought to relate the presence of specific microbes, gene expression, and tumor immune infiltration using tumor transcriptomics from The Cancer Genome Atlas (TCGA) and associate these with overall survival (OS). RNA sequencing (RNAseq) from HNSCC tumors in TCGA was processed through the exogenous sequences in tumors and immune cells (exotic) pipeline to identify and quantify low-abundance microbes. The detection of the Papillomaviridae family of viruses assessed HPV status. All statistical analyses were performed using R. A total of 499 RNAseq samples from TCGA were analyzed. HPV was detected in 111 samples (22%), most commonly Alphapapillomavirus 9 (90.1%). The presence of Alphapapillomavirus 9 was associated with improved OS [HR = 0.60 (95%CI: 0.40-0.89, p = .01)]. Among other microbes, Yersinia pseudotuberculosis was associated with the worst survival (HR = 3.88; p = .008), while Pseudomonas viridiflava had the best survival (HR = 0.05; p = .036). Microbial species found more abundant in HPV- tumors included several gram-negative anaerobes. HPV- tumors had a significantly higher abundance of M0 (p < .001) and M2 macrophages (p = .035), while HPV+ tumors had more T regulatory cells (p < .001) and CD8+ T-cells (p < .001). We identified microbes in HNSCC tumor samples significantly associated with survival. A greater abundance of certain anaerobic microbes was seen in HPV tumors and pro-tumorigenic macrophages. These findings suggest that TME can be used to predict patient outcomes and may help identify mechanisms of resistance to systemic therapies.

Electrochemotherapy as palliative care in patients with local or metastatic recurrence of head and neck cancer: review of state of the art.

Head and neck cancers are mostly represented by squamous cell carcinoma. Despite effective treatment of primary tumours, local recurrences and metastases are frequent, with up to a 60% risk of local and 30% of distant failure. Moreover, second primary tumours sometimes occur in these patients (2-3% per year). Treatment of recurrences, metastases, and second primary tumours can be extremely challenging for Otorhinolaryngologists, especially in patients who have already been treated with radiotherapy, previous surgery, or both. Electrochemotherapy represents an effective and valid option in these cases.

Interventional radiotherapy (brachytherapy) for re-irradiation of recurrent head and neck malignancies: oncologic outcomes and morbidity.

Objective: Management of recurrent head and neck cancer (HNC) is challenging. One option in previously irradiated patients is re-irradiation using interventional radiotherapy (IRT), the modern form of brachytherapy. Re-irradiation using IRT can be delivered as an exclusive strategy for salvage or through a postoperative or perioperative approach after salvage surgery. The aim of the present study is to analyse a bicentric Italian series focusing on the use of IRT as a re-irradiation modality and assess the resulting evidence concerning oncologic outcomes and morbidity. Methods: This is a retrospective study performed in two referral centres in Italy: Policlinico Universitario Agostino Gemelli in Rome and Azienda Ospedaliera Universitaria in Sassari. All patients who had previously received a full course of external beam RT and have been re-irradiated using high-dose-rate IRT between December 2010 and June 2023 were included. Patients were retreated either by a combination of surgery and perioperative (either endocavitary or interstitial) IRT or by exclusive interstitial IRT. Results: Thirty-four patients were included in the present series, 2 of whom underwent more than one IRT re-irradiation. Notably, no patient reported specific IRT-related toxicities. Median follow-up, excluding patients who died of HNC, was 24.5 months. Two-year local relapse-free survival was 26%, disease-specific survival 39.1%, and overall survival 36.6%. Conclusions: The present series is the largest reported experience of re-irradiation by IRT for HNC in Italy. The very low rate of toxicity confirms IRT as the safest re-irradiation modality. It is noteworthy to underline that IRT is a multidisciplinary strategy based on the close cooperation between surgeons and radiation oncologists during every phase, from the recommendation of treatment and implantation in the operating theatre, to its prescription and dose painting.

Bone reconstruction using CAD/CAM technology in head and neck surgical oncology. A narrative review of state of the art and aesthetic-functional outcomes.

Bone defects following resections for head and neck tumours can cause significant functional and aesthetic defects. The choice of the optimal reconstructive method depends on several factors such as the size of the defect, location of the tumour, patient's health and surgeon's experience. The reconstructive gold standard is today represented by revascularised osteo-myocutaneous or osteomuscular flaps with osteosynthesis using titanium plates. Commonly used donor sites are the fibula, iliac crest, and lateral scapula/scapular angle. In recent years, computer-aided design (CAD)/computer assisted manufacturing (CAM) systems have revolutionised the reconstructive field, with the introduction of stereolithographic models, followed by virtual planning software and 3D printing of plates and prostheses. This technology has demonstrated excellent reliability in terms of accuracy, precision and predictability, leading to better operative outcomes, reduced surgical times and decreased complication rates. Among the disadvantages are high costs, implementation times and poor planning adaptability. These problems are finding a partial solution in the development of "in house" laboratories for planning and 3D printing. Strong indications for the use of CAD/CAM technologies today are the reconstruction of total or subtotal mandibular or maxillary defects and secondary bone reconstructions.

Transcriptomic analysis-guided assessment of precision-cut tumor slices (PCTS) as an ex-vivo tool in cancer research.

With cancer immunotherapy and precision medicine dynamically evolving, there is greater need for pre-clinical models that can better replicate the intact tumor and its complex tumor microenvironment (TME). Precision-cut tumor slices (PCTS) have recently emerged as an ex vivo human tumor model, offering the opportunity to study individual patient responses to targeted therapies, including immunotherapies. However, little is known about the physiologic status of PCTS and how culture conditions alter gene expression. In this study, we generated PCTS from head and neck cancers (HNC) and mesothelioma tumors (Meso) and undertook transcriptomic analyses to understand the changes that occur in the timeframe between PCTS generation and up to 72 h (hrs) in culture. Our findings showed major changes occurring during the first 24 h culture period of PCTS, involving genes related to wound healing, extracellular matrix, hypoxia, and IFNγ-dependent pathways in both tumor types, as well as tumor-specific changes. Collectively, our data provides an insight into PCTS physiology, which should be taken into consideration when designing PCTS studies, especially in the context of immunology and immunotherapy.

Investigating oral somatosensory perception and oral symptoms of head and neck cancer patients: insights on eating behaviour.

PURPOSE: Sensory alterations and oral manifestations are prevalent among head and neck cancer (HNC) patients. While taste and smell alterations have been thoroughly investigated, studies on their oral somatosensory perception remain limited. Building upon our previous publication that primarily focused on objective somatosensory measurements, the present work examined self-reported sensory perception, including somatosensation and oral symptoms, in HNC patients and evaluated their link with eating behaviour. METHODS: A cross-sectional study was conducted using self-reported questionnaires on sensory perception, oral symptoms, sensory-related food preference, and eating behaviour among HNC patients (n = 30). Hierarchical clustering analysis was performed to categorise patients based on their sensory perception. Correlations between oral symptoms score, sensory perception, sensory-related food preference, and eating behaviour were explored. RESULTS: Two distinct sensory profiles of patients were identified: no alteration (n = 14) and alteration (n = 16) group. The alteration group showed decreased preference towards several sensory modalities, especially the somatosensory. Concerning eating behaviour, more patients in the alteration group agreed to negatively connotated statements (e.g. having food aversion and eating smaller portions), demonstrating greater eating difficulties. In addition, several oral symptoms related to salivary dysfunction were reported. These oral symptoms were correlated with sensory perception, sensory-related food preference, and eating behaviour. CONCLUSION: This study presented evidence demonstrating that sensory alterations in HNC patients are not limited to taste and smell but cover somatosensory perception and are linked to various aspects of eating. Moreover, patients reported experiencing several oral symptoms. Those with sensory alterations and oral symptoms experienced more eating difficulties.

Developing and validating multi-omics prediction models for late patient-reported dysphagia in head and neck radiotherapy.

Background and purpose. To investigate models developed using radiomic and dosiomic (multi-omics) features from planning and treatment imaging for late patient-reported dysphagia in head and neck radiotherapy.Materials and methods. Training (n = 64) and testing (n = 23) cohorts of head and neck cancer patients treated with curative intent chemo-radiotherapy with a follow-up time greater than 12 months were retrospectively examined. Patients completed the MD Anderson Dysphagia Inventory and a composite score ≤60 was interpreted as patient-reported dysphagia. A chart review collected baseline dysphagia and clinical factors. Multi-omic features were extracted from planning and last synthetic CT images using the pharyngeal constrictor muscle contours as a region of interest. Late patient-reported dysphagia models were developed using a random forest backbone, with feature selection and up-sampling methods to account for the imbalanced data. Models were developed and validated for multi-omic feature combinations for both timepoints.Results. A clinical and radiomic feature model developed using the planning CT achieved good performance (validation: sensitivity = 80 ± 27% / balanced accuracy = 71 ± 23%, testing: sensitivity = 80 ± 10% / balanced accuracy = 73 ± 11%). The synthetic CT models did not show improvement over the plan CT multi-omics models, with poor reliability of the radiomic features on these images. Dosiomic features extracted from the synthetic CT showed promise in predicting late patient-reported dysphagia.Conclusion. Multi-omics models can predict late patient-reported dysphagia in head and neck radiotherapy patients. Synthetic CT dosiomic features show promise in developing successful models to account for changes in delivered dose distribution. Multi-center or prospective studies are required prior to clinical implementation of these models.

Acupuncture for Chronic Radiation-Induced Xerostomia in Head and Neck Cancer: A Multicenter Randomized Clinical Trial.

Importance: Patients with head and neck cancer who undergo radiotherapy can develop chronic radiation-induced xerostomia. Prior acupuncture studies were single center and rated as having high risk of bias, making it difficult to know the benefits of acupuncture for treating radiation-induced xerostomia. Objective: To compare true acupuncture (TA), sham acupuncture (SA), and standard oral hygiene (SOH) for treating radiation-induced xerostomia. Design, Setting, and Participants: A randomized, blinded, 3-arm, placebo-controlled trial was conducted between July 29, 2013, and June 9, 2021. Data analysis was performed from March 9, 2022, through May 17, 2023. Patients reporting grade 2 or 3 radiation-induced xerostomia 12 months or more postradiotherapy for head and neck cancer were recruited from community-based cancer centers across the US that were part of the Wake Forest National Cancer Institute Community Oncology Research Program Research Base. Participants had received bilateral radiotherapy with no history of xerostomia. Interventions: Participants received SOH and were randomized to TA, SA, or SOH only. Participants in the TA and SA cohorts were treated 2 times per week for 4 weeks. Those experiencing a minor response received another 4 weeks of treatment. Main Outcomes and Measures: Patient-reported outcomes for xerostomia (Xerostomia Questionnaire, primary outcome) and quality of life (Functional Assessment of Cancer Therapy-General) were collected at baseline, 4 (primary time point), 8, 12, and 26 weeks. All analyses were intention to treat. Results: A total of 258 patients (201 men [77.9%]; mean [SD] age, 65.0 [9.16] years), participated from 33 sites across 13 states. Overall, 86 patients were assigned to each study arm. Mean (SD) years from diagnosis was 4.21 (3.74) years, 67.1% (n = 173) had stage IV disease. At week 4, Xerostomia Questionnaire scores revealed significant between-group differences, with lower Xerostomia Questionnaire scores with TA vs SOH (TA: 50.6; SOH: 57.3; difference, -6.67; 95% CI, -11.08 to -2.27; P = .003), and differences between TA and SA (TA: 50.6; SA: 55.0; difference, -4.41; 95% CI, -8.62 to -0.19; P = .04) yet did not reach statistical significance after adjustment for multiple comparisons. There was no significant difference between SA and SOH. Group differences in Functional Assessment of Cancer Therapy-General scores revealed statistically significant group differences at week 4, with higher scores with TA vs SOH (TA: 101.6; SOH: 97.7; difference, 3.91; 95% CI, 1.43-6.38; P = .002) and at week 12, with higher scores with TA vs SA (TA: 102.1; SA: 98.4; difference, 3.64; 95% CI, 1.10-6.18; P = .005) and TA vs SOH (TA: 102.1; SOH: 97.4; difference, 4.61; 95% CI, 1.99-7.23; P = .001). Conclusions and Relevance: The findings of this trial suggest that TA was more effective in treating chronic radiation-induced xerostomia 1 or more years after the end of radiotherapy than SA or SOH. Trial Registration: ClinicalTrials.gov Identifier: NCT02589938.

Breaking Ground in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: Novel Therapies Beyond PD-L1 Immunotherapy.

The treatment for recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) with immune checkpoint inhibitors (anti-PD1) with or without chemotherapy has led to an improvement in survival. Yet, despite this therapeutic advancement, only 15%-19% of patients remain alive at four years, highlighting the poor survival and unmet need for improved therapies for this patient population. Some of the key evolving novel therapeutics beyond anti-PD1 in R/M HNSCC have included therapeutic vaccine therapies, bispecific antibodies/fusion proteins and multitargeted kinase inhibitors, and antibody-drug conjugates (ADCs). Multiple concurrent investigations of novel therapeutics for patients with R/M HNSCC beyond anti-PD(L)1 inhibition are currently underway with some promising early results. Beyond immune checkpoint inhibition, novel immunotherapeutic strategies including therapeutic vaccines ranging from targeting human papillomavirus-specific epitopes to personalized neoantigen vaccines are ongoing with some early efficacy signals and large, randomized trials. Other novel weapons including bispecific antibodies, fusion proteins, and multitargeted kinase inhibitors leverage multiple concurrent targets and modulation of the tumor microenvironment to harness antitumor immunity and inhibition of protumorigenic signaling pathways with emerging promising results. Finally, as with other solid tumors, ADCs remain a promising therapeutic intervention either alone or in combination with immunotherapy for patients with R/M HNSCC. With early enthusiasm across novel therapies in R/M HNSCC, results of larger randomized trials in R/M HNSCC are eagerly awaited.

Quality of life, craniomandibular function, and psychosocial factors related to pain and movement in patients with head and neck cancer.

PURPOSE: To describe the characteristics of and the associations between health-related quality of life, pain, craniomandibular function, and psychosocial factors related to pain and fear of movement in patients with head and neck cancer. METHODS: Seventy-eight patients diagnosed with HNC were recruited. Measurements of the maximum mouth opening range and pressure pain thresholds on the masseter muscle and the distal phalanx of the thumb were conducted, as well as a battery of self-report questionnaires were administrated, including the QoL Questionnaire (EORT QLQ-H&N35), Numeric Rating Scale (NRS), Pain Catastrophizing Scale (PCS), the Spanish translation of the Tampa Scale for Kinesiophobia for Temporomandibular Disorders (TSK-TMD), and the short version of the Craniofacial Pain and Disability Inventory (CF-PDI-11). RESULTS: The study sample (66.7% men, mean age 60.12 [11.95] years) experienced a moderate impact on their QoL levels (57.68 [18.25] EORT QLQ-H&N35) and high kinesiophobia values (20.49 [9.11] TSK-TMD). Pain was present in 41% of the patients, but only 3.8% reported severe pain. 26.4% had a restricted mouth opening range, and 34.62% showed significant catastrophism levels. There were strong positive correlations between EORT QLQ-H&N35 and CF-PDI-11 (r = 0.81), between NRS and CF-PDI-11 (r = 0.74), and between PCS and CF-PDI-11 (r = 0.66). CONCLUSION: Patients with HNC experience negative effects in their QoL, related to their impairment in craniomandibular function. Fear of movement, pain intensity, and catastrophism are associated with poorer functionality; relationships that should be considered when attempting to improve health care.

Phase I quality control framework for monitoring organ-at-risk dose.

Objective.The aim of this work was to develop a Phase I control chart framework for the recently proposed multivariate risk-adjusted Hotelling'sT2chart. Although this control chart alone can identify most patients receiving extreme organ-at-risk (OAR) dose, it is restricted by underlying distributional assumptions, making it sensitive to extreme observations in the sample, as is typically found in radiotherapy plan quality data such as dose-volume histogram (DVH) points. This can lead to slightly poor-quality plans that should have been identified as out-of-control (OC) to be signaled in-control (IC).Approach. We develop a robust iterative control chart framework to identify all OC patients with abnormally high OAR dose and improve them via re-optimization to achieve an IC sample prior to establishing the Phase I control chart, which can be used to monitor future treatment plans.Main Results. Eighty head-and-neck patients were used in this study. After the first iteration, P14, P67, and P68 were detected as OC for high brainstem dose, warranting re-optimization aimed to reduce brainstem dose without worsening other planning criteria. The DVH and control chart were updated after re-optimization. On the second iteration, P14, P67, and P68 were IC, but P40 was identified as OC. After re-optimizing P40's plan and updating the DVH and control chart, P40 was IC, but P14* (P14's re-optimized plan) and P62 were flagged as OC. P14* could not be re-optimized without worsening target coverage, so only P62 was re-optimized. Ultimately, a fully IC sample was achieved. Multiple iterations were needed to identify and improve all OC patients, and to establish a more robust control limit to monitor future treatment plans.Significance. The iterative procedure resulted in a fully IC sample of patients. With this sample, a more robust Phase I control chart that can monitor OAR doses of new plans was established.

Identification of immunogenic cell death-related damage-related molecular patterns (DAMPs) to predict outcomes in patients with head and neck squamous cell carcinoma.

PURPOSE: Head and neck cancer is the sixth most common type of cancer worldwide, wherein the immune responses are closely associated with disease occurrence, development, and prognosis. Investigation of the role of immunogenic cell death-related genes (ICDGs) in adaptive immune response activation may provide cues into the mechanism underlying the outcome of HNSCC immunotherapy. METHODS: ICDGs expression patterns in HNSCC were analyzed, after which consensus clustering in HNSCC cohort conducted. A 4-gene prognostic model was constructed through LASSO and Cox regression analyses to analyze the prognostic index using the TCGA dataset, followed by validation with two GEO datasets. The distribution of immune cells and the response to immunotherapy were compared between different risk subtypes through multiple algorithms. Moreover, immunohistochemical (IHC) analyses were conducted to validate the prognostic value of HSP90AA1 as a predictor of HNSCC patient prognosis. In vitro assays were performed to further detect the effect of HSP90AA1 in the development of HNSCC. RESULTS: A novel prognostic index based on four ICDGs was constructed and proved to be useful as an independent factor of HNSCC prognosis. The risk score derived from this model grouped patients into high- and low-risk subtypes, wherein the high-risk subtype had worse survival outcomes and poorer immunotherapy response. IHC analysis validated the applicability of HSP90AA1 as a predictor of prognosis of HNSCC patients. HSP90AA1 expression in tumor cells promotes the progression of HNSCC. CONCLUSIONS: Together, these results highlight a novel four-gene prognostic signature as a valuable tool to assess survival status and prognosis of HNSCC patients.

A comparison between full-length 16S rRNA Oxford nanopore sequencing and Illumina V3-V4 16S rRNA sequencing in head and neck cancer tissues.

Describing the microbial community within the tumour has been a key aspect in understanding the pathophysiology of the tumour microenvironment. In head and neck cancer (HNC), most studies on tissue samples have only performed 16S rRNA short-read sequencing (SRS) on V3-V5 region. SRS is mostly limited to genus level identification. In this study, we compared full-length 16S rRNA long-read sequencing (FL-ONT) from Oxford Nanopore Technology (ONT) to V3-V4 Illumina SRS (V3V4-Illumina) in 26 HNC tumour tissues. Further validation was also performed using culture-based methods in 16 bacterial isolates obtained from 4 patients using MALDI-TOF MS. We observed similar alpha diversity indexes between FL-ONT and V3V4-Illumina. However, beta-diversity was significantly different between techniques (PERMANOVA - R2 = 0.131, p < 0.0001). At higher taxonomic levels (Phylum to Family), all metrics were more similar among sequencing techniques, while lower taxonomy displayed more discrepancies. At higher taxonomic levels, correlation in relative abundance from FL-ONT and V3V4-Illumina were higher, while this correlation decreased at lower levels. Finally, FL-ONT was able to identify more isolates at the species level that were identified using MALDI-TOF MS (75% vs. 18.8%). FL-ONT was able to identify lower taxonomic levels at a better resolution as compared to V3V4-Illumina 16S rRNA sequencing.

[Concurrent simultaneous integrated boost radiotherapy and cetuximab in head and neck squamous cell cancer patients: is it feasible in daily clinical practice?] / Radioterapia a intensità modulata con boost simultaneo più cetuximab in pazienti con carcinoma a cellule squamose in stadio localmente avanzato del distretto testa collo: è fattibile nella pratica clinica quotidiana?

INTRODUCTION AND AIM: Locally advanced head and neck squamous cell carcinoma (LA-Hnscc) is a true therapeutical challenge in the modern era and the scientific community is trying to face this challenge with new therapeutical strategies, including combinations of monoclonal antibodies and radiation therapy. The aim of this study is to evaluate clinical outcomes in LA-Hnscc patients unfit to receive platinum-based chemotherapy, treated with concurrent simultaneous integrated boost-intensity modulated radiotherapy (Sib-Imrt) + cetuximab (Ctx) in daily clinical practice. METHODS: LA-Hnscc patients not included in other prospective studies treated in 4 Italian radiotherapy units (2 Messina, 1 Rome, and 1 Lecce) using Sib-Imrt and Ctx were included in this study. Acute and late toxicities and overall survival (OS) have been evaluated. RESULTS: Data regarding 27 patients with squamous tumour were collected and reviewed. The primary tumour sites were oropharynx in 14 patients (51.9%), oral cavity in 7 (25.9%), larynx in 3 (11%) and other sites in 3(11%). There were 20 (74%) patients had stage IV (16 IVa and 4 IVb). Complete remission was observed in 18 patients (66.7%), a partial remission in 4 (14.8%) whilst 4 had a progression disease (14.8%). After 3 year of follow-up 7/27 patients were deaths. The OS was 95.5%, 62.5% and 52.9% respectively at 1,2 and 3 years. Acute toxicities were observed in all treated patients (mucositis, dermatitis and dysphagia) while 66.7% of patients developed late toxicities. All observed toxicities were grade 1 to 3 and just 1 patient developed a G4 toxicity. CONCLUSION: The concurrent bio-radiotherapy of Sib-Imrt and cetuximab is feasible in real-life daily clinical practice for LA-Hnscc patients unfit for platinum-based chemoradiotherapy.