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INTRODUCTION: Surgery is still the main line of treatment for papillary thyroid cancer (PTC) with a current trend for de-intensified treatment based on an excellent prognosis. The role of a routine prophylactic central neck dissection (PCND) is still debated as its impact on oncologic outcomes has never been cleared by a randomized clinical trial. In this study, we aimed to report our long-standing experience in PCND and its potential contemporary role in the treatment of PTC. METHODS: A retrospective institutional review was performed on all patients who underwent operation for PTC including PCND between 1998 and 2021. The primary outcomes were the rate of central lymph node metastases (CLNMs), cancer recurrence and incidence of complications. Survivals were analyzed using the Kaplan-Meier estimator and Cox proportional hazard models. RESULTS: A total of 657 patients were included in this study with a median follow-up of 78 months (48-114 months). Two hundred and one patients presented occult CLNMs (30.6%). The presence of a pathological node represented the unique reason for a completion thyroidectomy and I131 therapy in 12.5% of the population. Age lower than 55 years, microscopic or macroscopic extra-thyroid extension (ETE) and multifocality were independent factors predicting CLNMs. The rate of recurrence in the whole population was 2.7% (18 patients). Five-year and ten-year disease-free survival (DFS) was 96.5% (94.7-97.7) and 93.3% (90.3-95.5), respectively. Two patients relapsed in the central neck compartment (0.3%). Age (>55 years), pathological staging (pT) and extranodal extension (ENE) were independent factors associated with a worse DFS. The rate of temporary and permanent vocal fold palsy was 12.8% and 1.8%, respectively, and did not depend on the type of surgical procedure performed. Hypoparathyroidism was temporary in 42.2% and permanent in 11.9% of the patients. A sub-analysis upon cT1b-T2 patients treated primarily with thyroid lobectomy and ipsilateral PCND demonstrated a 2.6% rate of permanent hypoparathyroidism. CONCLUSIONS: PCND allows for a high disease-free survival and a proper selection of patients needing adjuvant treatment, in particular, those treated with a unilateral procedure. On the other hand, bilateral approach is burdened by a not-neglectable rate of permanent hypoparathyroidism.
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This article describes how the transcriptional alterations of the innate immune system divide dysplasias into aggressive forms that, despite the treatment, relapse quickly and more easily, and others where the progression is slow and more treatable. It elaborates on how the immune system can change the extracellular matrix, favoring neoplastic progression, and how infections can enhance disease progression by increasing epithelial damage due to the loss of surface immunoglobulin and amplifying the inflammatory response. We investigated whether these dysregulated genes were linked to disease progression, delay, or recovery. These transcriptional alterations were observed using the RNA-based next-generation sequencing (NGS) panel Oncomine Immune Response Research Assay (OIRRA) to measure the expression of genes associated with lymphocyte regulation, cytokine signaling, lymphocyte markers, and checkpoint pathways. During the analysis, it became apparent that certain alterations divide dysplasia into two categories: progressive or not. In the future, these biological alterations are the first step to provide new treatment modalities with different classes of drugs currently in use in a systemic or local approach, including classical chemotherapy drugs such as cisplatin and fluorouracile, older drugs like fenretinide, and new checkpoint inhibitor drugs such as nivolumab and pembrolizumab, as well as newer options like T cell therapy (CAR-T). Following these observed alterations, it is possible to differentiate which dysplasias progress or not or relapse quickly. This information could, in the future, be the basis for determining a close follow-up, minimizing surgical interventions, planning a correct and personalized treatment protocol for each patient and, after specific clinical trials, tailoring new drug treatments.
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Transcriptoma , Humanos , Perfilação da Expressão Gênica/métodos , Neoplasias Laríngeas/genética , Neoplasias Laríngeas/patologia , Sequenciamento de Nucleotídeos em Larga EscalaRESUMO
PURPOSE: Radiomics is an emerging field that utilizes quantitative features extracted from medical images to predict clinically meaningful outcomes. Validating findings is crucial to assess radiomics applicability. We aimed to validate previously published magnetic resonance imaging (MRI) radiomics models to predict oncological outcomes in oral tongue squamous cell carcinoma (OTSCC). MATERIALS AND METHODS: Retrospective multicentric study on OTSCC surgically treated from 2010 to 2019. All patients performed preoperative MRI, including contrast-enhanced T1-weighted (CE-T1), diffusion-weighted sequences and apparent diffusion coefficient map. We evaluated overall survival (OS), locoregional recurrence-free survival (LRRFS), cause-specific mortality (CSM). We elaborated different models based on clinical and radiomic data. C-indexes assessed the prediction accuracy of the models. RESULTS: We collected 112 consecutive independent patients from three Italian Institutions to validate the previously published MRI radiomic models based on 79 different patients. The C-indexes for the hybrid clinical-radiomic models in the validation cohort were lower than those in the training cohort but remained > 0.5 in most cases. CE-T1 sequence provided the best fit to the models: the C-indexes obtained were 0.61, 0.59, 0.64 (pretreatment model) and 0.65, 0.69, 0.70 (posttreatment model) for OS, LRRFS and CSM, respectively. CONCLUSION: Our clinical-radiomic models retain a potential to predict OS, LRRFS and CSM in heterogeneous cohorts across different centers. These findings encourage further research, aimed at overcoming current limitations, due to the variability of imaging acquisition, processing and tumor volume delineation.
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Imageamento por Ressonância Magnética , Neoplasias da Língua , Humanos , Neoplasias da Língua/diagnóstico por imagem , Neoplasias da Língua/patologia , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Imageamento por Ressonância Magnética/métodos , Idoso , Prognóstico , Adulto , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/mortalidade , RadiômicaRESUMO
Objective: To perform a dosimetric comparison between intensity modulated radiotherapy (IMRT) and 3D conformal radiotherapy in patients with locally advanced (stage III and IV) tumours of the supraglottic region treated with conservative surgery and post-operative radiotherapy. Methods: An in-silico plan using a 3D conformal shrinking field technique was retrospectively produced for 20 patients and compared with actually delivered IMRT plans. Eighteen structures (arytenoids, constrictor muscles, base of tongue, floor of mouth, pharyngeal axis, oral cavity, submandibular glands and muscles of the swallowing functional units [SFU]) were considered. Results: IMRT allowed a reduction of maximum and mean doses to 9 and 14 structures, respectively (p < .05). Conclusions: IMRT achieved a reduction of unnecessary dose to the remnant larynx and the majority of surrounding SFUs. Further prospective analyses and correlations with functional clinical outcomes are required to confirm these dosimetric findings.
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Neoplasias Laríngeas , Radioterapia Conformacional , Radioterapia de Intensidade Modulada , Humanos , Neoplasias Laríngeas/radioterapia , Neoplasias Laríngeas/cirurgia , Radioterapia Conformacional/métodos , Masculino , Radioterapia de Intensidade Modulada/métodos , Estudos Retrospectivos , Feminino , Pessoa de Meia-Idade , Idoso , Dosagem Radioterapêutica , Adulto , Cuidados Pós-Operatórios/métodosRESUMO
PURPOSE: Salvage surgery is still the best therapeutic option for resectable recurrent oropharyngeal squamous cell carcinoma (rOPSCC). Transoral robotic surgery may potentially reduce the morbidity of standard open approaches. The aim of the study is to present oncological and functional outcomes of a monocentric experience in salvage transoral robotic surgery. METHODS: We performed a single-center retrospective analysis of patients submitted to transoral robotic salvage surgery with or without neck dissection for cT1-3 rOPSCC. We investigated complication rate, survival outcomes (Overall Survival, Disease Specific Survival, Loco-Regional Recurrence Free Survival) and functional outcomes (tracheal tube and/or gastrostomy dependence). RESULTS: Sixty-one patients were included in the analysis. No major complications or perioperative deaths were recorded. The estimated 2-year OS was 76.7%, DSS 81.8% and LRRFS 50.5%. In multivariable analysis rpT, PNI (perineural infiltration) and HPV-positivity were significantly associated with LRRFS (Hazard Ratios: T3 vs T1 6.43, PNI yes vs no 4.19, HPV+ yes vs no 2.63). At last follow up, 97% of patients were tracheal tube-free, while 93% were gastrostomy-free. CONCLUSION: Transoral robotic salvage surgery is a successful treatment in selected patients affected by rOPSCC because it grants good oncologic and functional outcomes.
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Carcinoma de Células Escamosas , Recidiva Local de Neoplasia , Neoplasias Orofaríngeas , Procedimentos Cirúrgicos Robóticos , Terapia de Salvação , Humanos , Procedimentos Cirúrgicos Robóticos/métodos , Estudos Retrospectivos , Masculino , Terapia de Salvação/métodos , Neoplasias Orofaríngeas/cirurgia , Neoplasias Orofaríngeas/patologia , Neoplasias Orofaríngeas/mortalidade , Feminino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia , Idoso , Carcinoma de Células Escamosas/cirurgia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/mortalidade , Esvaziamento Cervical/métodos , Adulto , Resultado do Tratamento , Cirurgia Endoscópica por Orifício Natural/métodos , Idoso de 80 Anos ou maisRESUMO
PURPOSE: The tracheoesophageal puncture for the voice prosthesis (VP) placement is the recognized gold standard in post-laryngectomy voice rehabilitation. Despite the development of specific intraoperative techniques, a subset of patients will suffer from poor functional outcomes due to pharyngoesophageal spasms (PES). This paper evaluates the functional outcomes after transcutaneous botulinum toxin type A (BTX-A) infiltration for PES with a videofluoroscopy-guided technique. METHODS: Since 2022, eight consecutive patients with VP and affected by PES were treated with BTX-A injection by a standard videofluoroscopic guided technique at the European Institute of Oncology, IRCCS (IEO) in Milan. A lidocaine test was performed pre-operatively to evaluate the potential effect of chemical neurectomy. All patients with positive lidocaine tests were injected with 50 IU of BTX-A (Allergan, Irvine, CA) according to the sites marked during the videofluoroscopy. Reported symptoms (VHI, SECEL), perceptual (INFVo), aerodynamic (MPT) and manometric parameters were collected before and after treatment. RESULTS: In all cases, BTX-A was performed as an outpatient procedure without complications. For seven patients, only one BTX-A injection was needed, while one patient required a re-injection. Subjective and perceptive improvement after BTX-A was significant for VHI, SECEL and INFVo. MPT showed significant improvement after a chemical neurectomy. After a mean follow-up of 6 months, all patients maintained a good TES quality. CONCLUSION: The videofluoroscopic guided BTX-A injection of the pharyngoesophageal tract showed to be a feasible and reproducible technique in all cases. The pharyngoesophageal videofluoroscopy allows defining of patients' anatomical landmarks that help the surgeon to perform a homogeneous injection, empowered by post-injection massage.
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Toxinas Botulínicas Tipo A , Humanos , Fala , Laringectomia/efeitos adversos , Voz Esofágica , Espasmo/etiologia , Lidocaína , Resultado do TratamentoRESUMO
PURPOSE: To evaluate efficacy and toxicity of carbon ion radiotherapy (CIRT) in locally advanced head and neck mucosal melanoma (HNMM) patients treated at our Institute. MATERIALS AND METHODS: Between June 2013 and June 2020, 40 HNMM patients were treated with CIRT. Prescription dose was 65.6-68.8 Gy relative biological effectiveness [RBE] in 16 fractions. Twelve (30%) patients received only biopsy, 28 (70%) surgical resection before CIRT. Immunotherapy was administered before and/or after CIRT in 45% of patients, mainly for distant progression (89%). RESULTS: Median follow-up was 18 months. 2-year Local Relapse Free Survival (LRFS), Overall Survival (OS), Progression Free Survival (PFS) and Distant Metastasis Free Survival (DMFS) were 84.5%, 58.6%, 33.2% and 37.3%, respectively. At univariate analysis, LRFS was significantly better for non-recurrent status, < 2 surgeries before CIRT and treatment started < 9 months from the initial diagnosis, with no significant differences for operated versus unresected patients. After relapse, immunotherapy provided longer median OS (17 months vs 3.6, p-value<0.001). Late toxicity ≥ G3 (graded with CTCAE 5.0 scale) was reported in 10% of patients. CONCLUSION: CIRT in advanced HNMM patients is safe and locally effective. Prospective trials are warranted to assess the role of targeted/immune- systemic therapy to improve OS.
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Neoplasias de Cabeça e Pescoço , Radioterapia com Íons Pesados , Melanoma , Humanos , Melanoma/radioterapia , Melanoma/patologia , Estudos Prospectivos , Recidiva Local de Neoplasia/patologia , Neoplasias de Cabeça e Pescoço/radioterapia , Neoplasias de Cabeça e Pescoço/etiologia , Radioterapia com Íons Pesados/efeitos adversosRESUMO
PURPOSE: The neck management in early-stage cN0 supraglottic cancer represents an argument of debate. The aim of our study is to evaluate the oncological and functional outcomes in patients with early-stage cN0 supraglottic carcinoma treated with a wait-and-see policy for the neck. MATERIALS AND METHODS: Retrospective monocentric cohort study in a referral cancer care center. We collected a consecutive sample of patients from 2000 to 2020 with Squamous Cell Carcinoma of the supraglottis without clinical evidence of nodal metastases (cN0), surgically treated with Transoral Surgery (Laser or Robotic) without neck dissection. From 316 supraglottic cancer we finally selected 66 eligible participants that met all inclusion criteria. RESULTS: Sixty-six patients (M 75.8 % vs F 24.2 %), median age 65.8 years (IQR 60.9, 70.5). The most common subsite was the epiglottis (62.1 %). Tumor stage distribution was as follows: 35 % cT1, 53 % cT2, 15.2 % cT3. Neither deaths nor major treatment-related complications were reported after surgery. The median follow-up was 62 months. For oncological outcomes, we evaluated 56 patients (10 excluded for adjuvant radiotherapy): 5-year overall survival rate 87 % (CI 95 %: 73.1-94), disease- specific survival rate 95.3 % (CI 95 %: 82-98.8) and neck recurrence-free survival rate 87 % (CI 95 %: 73.1-94). Six patients developed neck recurrence, with a median time of 13 months. CONCLUSIONS: Supraglottic carcinoma has been historically associated to a considerable risk of occult metastasis. However, in early-stage cases data are still inconclusive. Our results suggest that in such patients a wait-and-see policy does not impact negatively on survival outcomes, while granting the reduced morbidity associated to a minimally invasive surgical approach.
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Carcinoma de Células Escamosas , Neoplasias Laríngeas , Humanos , Idoso , Neoplasias Laríngeas/patologia , Esvaziamento Cervical/métodos , Estudos Retrospectivos , Estudos de Coortes , Estadiamento de Neoplasias , Carcinoma de Células Escamosas/patologiaRESUMO
Autophagy is important for the removal, degradation and recycling of damaged organelles, proteins, and lipids through the degradative action of lysosomes. In addition to its catabolic function, autophagy is important in cancer and viral-mediated tumorigenesis, including Human Papillomavirus (HPV) positive cancers. HPV infection is a major risk factor in a subset of head and neck cancer (HNC), for which no targeted therapies are currently available. Herein, we assessed autophagy function in HPV-positive HNC. We showed that HPV-positive HNC cells presented a transcriptional and functional impairment of the autophagic process compared to HPV-negative cells, which were reactivated by knocking down HPV E6/E7 oncoproteins, the drivers of cellular transformation. We found that the oncoprotein c-MYC was stabilized and triggered in HPV-positive cell lines. This resulted in the reduced binding of the MiT/TFE transcription factors to their autophagy targets due to c-MYC competition. Thus, the knock-down of c-MYC induced the upregulation of autophagic and lysosomal genes in HPV-positive HNC cells, as well as the increase of autophagic markers at the protein level. Moreover, HPV oncoprotein E7 upregulated the expression of the phosphatase inhibitor CIP2A, accounting for c-MYC upregulation and stability in HPV+ HNC cells. CIP2A mRNA expression negatively correlated with autophagy gene expression in tumor tissues from HNC patients, showing, for the first time, its implication in a transcriptional autophagic context. Both CIP2A and c-MYC knock-down, as well as pharmacological downregulation of c-MYC, resulted in increased resistance to cisplatin treatment. Our results not only show a novel way by which HPV oncoproteins manipulate the host machinery but also provide more insights into the role of autophagy in chemoresistance, with possible implications for targeted HPV-positive HNC therapy.
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Autofagia , Neoplasias de Cabeça e Pescoço , Infecções por Papillomavirus , Proteínas Proto-Oncogênicas c-myc , Humanos , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/virologia , Proteínas E7 de Papillomavirus/genética , Proteínas E7 de Papillomavirus/metabolismo , Infecções por Papillomavirus/tratamento farmacológico , Infecções por Papillomavirus/genética , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismoRESUMO
We analyzed the inclusion of sex and/or gender (S/G) in Head and Neck Cancer (HNC) clinical studies, through inspecting ClinicalTrials.gov (AACT) and the mention of Human Papilloma Virus (HPV) on a specific subgroup, namely oral cavity, larynx and oropharynx. Only 5% of HNC studies mention S/G as a planned analytical variable. Proportionally more observational studies treated S/G as an analytical variable than interventional studies (10% vs 5%, P-value ≤ 0.001), 8% of studies that mentioned S/G involved more than 100 subjects while 4% less than 100 (P-value ≤ 0.001). In randomized protocols, S/G was mentioned more in studies with a planned sample of more than 100 patients and including HPV status (P-value < 0.05). Small controlled studies have lower mention of S/G as an analytical variable than uncontrolled studies (4% and 10%, respectively among studies with less than 100 subjects). Significantly greater mention of S/G as an analytical variable is observed in controlled and randomized studies with a sample size greater than 100 subjects. HPV was mentioned in only 18% of oral cavity-larynx-oropharynx studies. Interventional studies do not regularly account for S/G during HNC study design. Thus, although fundamental, in studies concerning HNC the S/G variable is often not considered. In trials published in scientific journals (P-value = 0.01) and in more recent clinical trials (P-value = 0.002), S/G is taken more into account suggesting an increasing awareness on its importance. However, the need to systematically include S/G in study design clearly emerges, to better highlight sex-related differences in disease incidence and prognosis and best imbue science and medicine with the proper biological and cultural differences.
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BACKGROUND: A multicentric study was conducted on technical reproducibility of compartmental tongue surgery (CTS) in advanced tongue cancers (OTSCC) and comparison to standard wide margin surgery (SWMS). METHODS: We studied 551 patients with OTSCC treated by CTS and 50 by SWMS. Oncological outcomes were analyzed. A propensity score was performed to compare survival endpoints for the two cohorts. RESULTS: In the CTS group, survival and prognosis were significantly associated with positive lymph-nodes, extranodal extension, depth of invasion and involvement of the soft tissue connecting the tongue primary tumor to neck lymph nodes (T-N tract), independently from the center performing the surgery. SWMS versus CTS showed a HR Cause-Specific Survival (CSS) of 3.24 (95% CI: 1.71-6.11; p < 0.001); HR Loco-Regional Recurrence Free Survival (LRRFS) of 2.54 (95% CI: 1.47-4.40; p < 0.001); HR Overall Survival (OS) of 0.11 (95% CI: 0.01-0.77; p = 0.03). CONCLUSION: Performing the CTS could provide better CSS and LRRFS than SWMS regardless of the center performing the surgery, in advanced OTSSC.
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Carcinoma de Células Escamosas , Neoplasias da Língua , Humanos , Reprodutibilidade dos Testes , Estadiamento de Neoplasias , Língua/cirurgia , Carcinoma de Células Escamosas/patologia , Neoplasias da Língua/patologia , Prognóstico , Estudos Retrospectivos , Recidiva Local de Neoplasia/patologiaRESUMO
AIMS: To assess whether CT-based radiomics and blood-derived biomarkers could improve the prediction of overall survival (OS) and locoregional progression-free survival (LRPFS) in patients with oropharyngeal cancer (OPC) treated with curative-intent RT. METHODS: Consecutive OPC patients with primary tumors treated between 2005 and 2021 were included. Analyzed clinical variables included gender, age, smoking history, staging, subsite, HPV status, and blood parameters (baseline hemoglobin levels, neutrophils, monocytes, and platelets, and derived measurements). Radiomic features were extracted from the gross tumor volumes (GTVs) of the primary tumor using pyradiomics. Outcomes of interest were LRPFS and OS. Following feature selection, a radiomic score (RS) was calculated for each patient. Significant variables, along with age and gender, were included in multivariable analysis, and models were retained if statistically significant. The models' performance was compared by the C-index. RESULTS: One hundred and five patients, predominately male (71%), were included in the analysis. The median age was 59 (IQR: 52-66) years, and stage IVA was the most represented (70%). HPV status was positive in 63 patients, negative in 7, and missing in 35 patients. The median OS follow-up was 6.3 (IQR: 5.5-7.9) years. A statistically significant association between low Hb levels and poorer LRPFS in the HPV-positive subgroup (p = 0.038) was identified. The calculation of the RS successfully stratified patients according to both OS (log-rank p < 0.0001) and LRPFS (log-rank p = 0.0002). The C-index of the clinical and radiomic model resulted in 0.82 [CI: 0.80-0.84] for OS and 0.77 [CI: 0.75-0.79] for LRPFS. CONCLUSIONS: Our results show that radiomics could provide clinically significant informative content in this scenario. The best performances were obtained by combining clinical and quantitative imaging variables, thus suggesting the potential of integrative modeling for outcome predictions in this setting of patients.
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INTRODUCTION: Care for head and neck cancers is complex in particular for the rare ones. Knowledge is limited and histological heterogeneity adds complexity to the rarity. There is a wide consensus that to support clinical research on rare cancer, clinical registries should be developed within networks specializing in rare cancers. In the EU, a unique opportunity is provided by the European Reference Networks (ERN). The ERN EURACAN is dedicated to rare adults solid cancers, here we present the protocol of the EURACAN registry on rare head and neck cancers (ClinicalTrials.gov Identifier: NCT05483374). STUDY DESIGN: Registry-based cohort study including only people with rare head and neck cancers. OBJECTIVES: to help describe the natural history of rare head and neck cancers;to evaluate factors that influence prognosis;to assess treatment effectiveness;to measure indicators of quality of care. METHODS: Settings and participants It is an hospital based registry established in hospitals with expertise in head and neck cancers. Only adult patients with epithelial tumours of nasopharynx; nasal cavity and paranasal sinuses; salivary gland cancer in large and small salivary glands; and middle ear will be included in the registry. This registry won't select a sample of patients. Each patient in the facility who meets the above mentioned inclusion criteria will be followed prospectively and longitudinally with follow-up at cancer progression and / or cancer relapse or patient death. It is a secondary use of data which will be collected from the clinical records. The data collected for the registry will not entail further examinations or admissions to the facility and/or additional appointments to those normally provided for the patient follow-up. Variables Data will be collected on patient characteristics (eg. patient demographics, lifestyle, medical history, health status); exposure data (eg. disease, procedures, treatments of interest) and outcomes (e.g. survival, progression, progression-free survival, etc.). In addition, data on potential confounders (e.g. comorbidity; functional status etc.) will be also collected. Statistical methods The data analyses will include descriptive statistics showing patterns of patients' and cancers' variables and indicators describing the quality of care. Multivariable Cox's proportional hazards model and Hazard ratios (HR) for all-cause or cause specific mortality will be used to determine independent predictors of overall survival, recurrence etc. Variables to include in the multivariable regression model will be selected based on the results of univariable analysis. The role of confounding or effect modifiers will be evaluated using stratified analysis or sensitivity analysis. To assess treatment effectiveness, multivariable models with propensity score adjustment and progression-free survival will be performed. Adequate statistical (eg. marginal structural model) methods will be used if time-varying treatments/confounders and confounding by indication (selective prescribing) will be present. RESULTS: The registry initiated recruiting in May 2022. The estimated completion date is December 2030 upon agreement on the achievement of all the registry objectives. As of October 2022, the registry is recruiting. There will be a risk of limited representativeness due to the hospital-based nature of the registry and to the fact that hospital contributing to the registry are expert centres for these rare cancers. Clinical Follow-up could also be an issue but active search of the life status of the patients will be guaranteed.
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Neoplasias de Cabeça e Pescoço , Humanos , Adulto , Estudos de Coortes , Neoplasias de Cabeça e Pescoço/epidemiologia , Neoplasias de Cabeça e Pescoço/terapia , Resultado do Tratamento , Modelos de Riscos Proporcionais , Sistema de RegistrosRESUMO
(1) Background: The development of laryngeal cancer is a multistep process involving structural alterations of the epithelial mucosa, from dysplasia (LDy) to invasive carcinoma. In this study, we define new biomarkers, prognostic for malignant transformation, in patients affected by LDy. (2) Methods: We used targeted next-generation sequencing and immunohistochemical analysis to define the mutational and immunological landscape of 15 laryngeal dysplasia progressing to invasive cancer (progressing dysplasia), as well as 31 cases of laryngeal dysplasia that did not progress to carcinoma (non-progressing dysplasia). Two pathologists independently analyzed the presence of tumor-infiltrating lymphocytes in LDy pre-embedded paraffin-fixed specimens. The RNA-based next-generation sequencing panel OIRRA was used to evaluate the expression of 395 genes related to immune system activation. (3) Results: High TILs are significantly correlated with a higher risk of malignant transformation. The non-brisk pattern was significantly associated with an 86% reduced risk of malignant progression (OR = 0.16, 95% CI: 0.03-0.5, p = 0.008). TILs showed a highly positive correlation with CCR6, CD83, HLA-DPB1, MX1 and SNAI1, and they were inversely correlated with CD48, CIITA, CXCR4, FCER1G, IL1B, LST1 and TLR8. (4) Conclusions: TILs have a great potential to identify high-risk progression dysplasia and thus to define surveillance protocols and prevention programs.
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The current study aims to profile sarcopenic condition (both at baseline and developed during treatment) in oropharyngeal carcinoma (OPC) patients treated with curative radiotherapy (RT) +/- chemotherapy and to evaluate its impact on oncological outcomes and toxicity. A total of 116 patients were included in this retrospective single-center study. Sarcopenia assessment at baseline and at 50 Gy re-evaluation CT was obtained from two different methodologies: (i) the L3-skeletal muscle index (SMI) derived from the contouring of the cross-sectional area (CSA) of the masticatory muscles (CSA-MM); and (ii) the paravertebral and sternocleidomastoid muscles at the level of the third cervical vertebra (CSA-C3). Based on L3-SMI from CSA-MM, developing sarcopenic condition during RT (on-RT sarcopenia) was associated with worse progression-free survival (PFS) (p = 0.03) on multivariable analysis and a trend of correlation with overall survival (OS) was also evident (p = 0.05). According to L3-SMI derived from CSA-C3, on-RT sarcopenia was associated with worse PFS (p = 0.0096) and OS (p = 0.013) on univariate analysis; these associations were not confirmed on multivariable analysis. A significant association was reported between becoming on-RT sarcopenia and low baseline haemoglobin (p = 0.03) and the activation of nutritional counselling (p = 0.02). No significant associations were found between sarcopenia and worse RT toxicity. Our data suggest that the implementation of prompt nutritional support to prevent the onset of sarcopenia during RT could improve oncological outcomes in OPC setting.
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BACKGROUND: Radiomics represents an emerging field of precision-medicine. Its application in head and neck is still at the beginning. METHODS: Retrospective study about magnetic resonance imaging (MRI) based radiomics in oral tongue squamous cell carcinoma (OTSCC) surgically treated (2010-2019; 79 patients). All preoperative MRIs include different sequences (T1, T2, DWI, ADC). Tumor volume was manually segmented and exported to radiomic-software, to perform feature extraction. Statistically significant variables were included in multivariable analysis and related to survival endpoints. Predictive models were elaborated (clinical, radiomic, clinical-radiomic models) and compared using C-index. RESULTS: In almost all clinical-radiomic models radiomic-score maintained statistical significance. In all cases C-index was higher in clinical-radiomic models than in clinical ones. ADC provided the best fit to the models (C-index 0.98, 0.86, 0.84 in loco-regional recurrence, cause-specific mortality, overall survival, respectively). CONCLUSION: MRI-based radiomics in OTSCC represents a promising noninvasive method of precision medicine, improving prognosis prediction before surgery.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias da Língua , Humanos , Estudos Retrospectivos , Neoplasias da Língua/diagnóstico por imagem , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/terapia , Prognóstico , Imageamento por Ressonância Magnética/métodos , Carcinoma de Células Escamosas de Cabeça e PescoçoRESUMO
BACKGROUND: The treatment of tongue tumors includes different surgical procedures ranging from a simple mucosal resection to complex combined resection depending on the tumor stage and size. In 2019 we reported an international glossectomy classification with the purpose of standardizing all the different types of surgical procedures adopted for tongue cancer. METHODS: The present communication aims at providing further insight into the glossectomy classification. More specifically, it is intended to better specify the indications to glossectomy type IIIA and B in selected tongue cancers, with positive cervical lymph nodes at the diagnosis. RESULTS AND CONCLUSIONS: Type IIIA glossectomy permits a high function sparing surgery in selected cases, with better postoperative functional outcomes. From an oncological perspective, it permits a radical surgery, avoiding postoperative radiation in the absence of extracapsular spread, multiple nodal metastases or T-N tract involvement.
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Carcinoma de Células Escamosas , Neoplasias da Língua , Humanos , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/cirurgia , Carcinoma de Células Escamosas/patologia , Neoplasias da Língua/diagnóstico , Neoplasias da Língua/cirurgia , Neoplasias da Língua/patologia , Linfonodos/cirurgia , Linfonodos/patologia , Esvaziamento Cervical , Estadiamento de Neoplasias , Língua/patologia , Estudos RetrospectivosRESUMO
OBJECTIVE: The space comprised between tumor and neck lymph nodes (T-N tract) is one of the main routes of tumor spread in oral cavity tumors. Aim of the study was to investigate the impact of T-N tract involvement on the postoperative radiotherapy (PORT) outcomes. MATERIALS AND METHODS: Patients (pts) treated between 2000 and 2016 with indication to PORT were retrospectively retrieved. Inclusion criteria were: (a) locally advanced tumors of the oral cavity, (b) who received with indication to PORT (c) with a minimum follow-up of six months. RESULTS: One hundred and fifty-seven pts met the inclusion criteria (136 pts treated with PORT and 21 pts not treated with PORT). In the PORT cohort, the T-N tract involvement had no impact on both OS (p = .09) and LRFS (p = .2). Among the non-PORT cohort, both OS (p = .007) and LRFS (p = .017) were worse for pts with positive T-N tract compared to those with negative T-N tract. PORT improved both OS (p = .008) and LRFS (p = .003) in pts with positive T-N tract but not in those with negative T-N tract (p = .36 and p = .37, respectively). CONCLUSIONS: Our results suggest that involvement of T-N tract should be considered as prognostic factors informing the indication to PORT.
Assuntos
Neoplasias Bucais , Humanos , Estadiamento de Neoplasias , Radioterapia Adjuvante , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias Bucais/radioterapiaRESUMO
Background: Women and men differ genetically, biologically (sex) and by social construct (gender), possibly impacting on prognostic factors in predicting cancer survival. Hemoglobin levels and immune system activation are players acting in this scenario which could play a role in partly determining prognosis between patients of different sex/gender (S/G). Here, we investigate these factors in patients affected by tongue squamous cell carcinoma. Methods: This is an observational retrospective cohort study. We collected tongue cancer patients' clinical data, including hemoglobin levels and neutrophil lymphocyte ratio (NLR). Overall survival (OS) and disease-free survival (DFS) were compared between women and men considering confounding and prognostic factors in multivariate Cox proportional hazard models. Stratified analyses were also conducted by sex and tumor stage. Result: 576 patients, 39.9% women and 60.1% men, were found eligible for the analysis. Men were more often smokers (p<0.001), alcohol consumers (p<0.001), overweight or obese (p<0.001) and undergoing radiotherapy (p=0.002). In multivariate models for stage I-II, men showed half risk of death and relapse compared to women (HR=0.44; 95%CI 0.24-0.81, p=0.009; HR=0.55; 95%CI 0.34-0.87, p=0.01, for OS and DFS respectively). Moreover, low hemoglobin levels appeared to be an independent prognostic factor for women but not for men in terms of both OS and DFS. Specifically, women with low hemoglobin levels showed a worse tumor outcome (HR=2.66; 95%CI 1.50-4.70; HR=2.09; 95%CI 1.24-3.53, for OS and DFS respectively). Low hemoglobin levels appeared to be a poor OS prognostic factor for women at stage I-II (p<0.004) but not for men (p=0.10). Women with advanced stage tumors, NLR>2.37, who did not performed Radiotherapy and with depth of invasion (DOI)> 10 were associated with a significant increase in relapse and death (all p<0.05). Conclusion: In our cohort of patients with oral tongue squamous cell carcinoma, men present better OS and DFS than women with early stages tumors. Low hemoglobin level was an independent prognostic factor for women, especially at early-stage tumors. For advanced stages (III-IV), sex is not a significant factor related to patients' prognosis.