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Background: This work evaluated the proportion of patients who continue therapy until their last month of life or initiate a new therapy in the last 3 months of life (end of life [EOL]). Methods: Data for 486 patients were retrospectively collected. Results: In EOL, 205 (42.3%) received systemic therapy. Better performance status (last month overall response [OR]: 0.39; 95% CI: 0.25-0.60; p < 0.001; last 3 months OR: 0.47; 95% CI: 0.34-0.65; p < 0.001) and lack of activation of palliative care (last month OR: 0.26; 95% CI: 0.13-0.54; p < 0.001; last 3 months OR: 0.18; 95% CI: 0.10-0.32; p < 0.001) were associated with higher probability of EOL therapy. Conclusion: A non-negligible proportion of patients in real-life settings continue to receive systemic treatment in EOL.
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Neoplasias , Assistência Terminal , Humanos , Estudos Retrospectivos , Cuidados Paliativos , Oncologia , Morte , Neoplasias/terapiaRESUMO
INTRODUCTION: Treatment of human papillomavirus (HPV)-related head and neck squamous cell carcinoma (HNSCC) is rapidly evolving. Despite either surgery or radiotherapy (RT), with or without chemotherapy (CT), being acceptable in intermediate and locally advanced diseases, there is uncertainty regarding the best treatment option for these patients. Therefore, we performed a network meta-analysis (NMA) to compare the relative efficacy of different treatments for HPV+ oropharyngeal carcinoma. MATERIAL AND METHODS: Randomized clinical trials that enrolled adults with non-metastatic HPV+ oropharynx cancer and provided data about overall survival (OS) and/or progression-free survival (PFS) and/or locoregional control and distant metastases (LRC and DM) were included. Fixed- or random-effects models were fit using a Bayesian approach to NMA. Between-group comparisons were estimated using hazard ratios (HRs) with 95% credible intervals (CrIs). The primary outcome was OS. RESULTS: A total of 844 citations were screened; 11 randomized clinical trials were included (HPV+ stage III-IV cancer, mainly oropharynx carcinomas). Nine treatment arms were compared. Radiotherapy (altered or standard fractionation) + triweekly cisplatin (HR 3.8; 95% CrIs 0.29-65 and 0.3; 95% CrIs 0.03-2.51) was superior to RT in term of OS (P score = 0.42 and 0.16). Radiotherapy with low and high cisplatin doses appeared similar (HR 1.57; 95% CrIs 0.19-12.72). Altered fractionation or standard RT + 3-weekly cisplatin are the 2 highest-ranked options in terms of PFS (P score = 0.35 and 0.34). CONCLUSIONS: This meta-analysis confirms the role of cisplatin added to RT as the best option for HPV+ oropharyngeal carcinoma. RT+ 3-weekly cisplatin is likely to be the best radical treatment in terms of OS and PFS.
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Neoplasias Orofaríngeas , Infecções por Papillomavirus , Carcinoma de Células Escamosas de Cabeça e Pescoço , Adulto , Humanos , Teorema de Bayes , Quimiorradioterapia , Cisplatino/uso terapêutico , Metanálise em Rede , Neoplasias Orofaríngeas/patologia , Neoplasias Orofaríngeas/terapia , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/terapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
PURPOSE: As the practice of nutritional support in patients with head and neck cancer (HNC) during curative radio(chemo)therapy is quite heterogeneous, we carried out a survey among European specialists. METHODS: A 19-item questionnaire was drawn up and disseminated via the web by European scientific societies involved in HNC and nutrition. RESULTS: Among 220 responses, the first choice was always for the enteral route; naso-enteral tube feeding was preferred to gastrostomy in the short term, while the opposite for period longer than 1 month. Indications were not solely related to the patient's nutritional status, but also to the potential burden of the therapy. CONCLUSION: European HNC specialists contextualize the use of the nutritional support in a comprehensive plan of therapy. There is still uncertainty relating to the role of naso-enteral feeding versus gastrostomy feeding in patients requiring < 1 month nutritional support, an issue that should be further investigated.
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Neoplasias de Cabeça e Pescoço , Intubação Gastrointestinal , Nutrição Enteral , Gastrostomia , Neoplasias de Cabeça e Pescoço/etiologia , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Oral Potentially Malignant Disorders (OPMD) have a non-negligible malignant transformation rate of up to 8%. Loss of heterozygosity (LOH) in critical chromosomal loci has proven to be the most effective marker in defining the risk of transformation and it is found in about 28% of OPMD and may therefore identify patients carrying higher risk. To date, clinical management of OPMD is limited to surgical excision and clinical surveillance, which however do not fully prevent oral cancer development. Immune system has been shown to play a key role in transformation surveillance mechanism and an immunosuppressive imbalance may be responsible for progression to cancer. Given all these considerations, we designed a clinical trial with the aim to prevent OPMD neoplastic transformation and revert the LOH status. METHODS: This is a phase II, open label, single arm, multicentric trial involving Italian referral centres and expected to enrol 80 patients out of a total of 175 screened. Patients who meet all inclusion criteria and test positive for LOH after an incisional biopsy of the OPMD will undergo a short course of immunotherapy with 4 administration of avelumab. After 6 months since treatment start, resection of the entire OPMD will be performed and LOH assessment will be repeated. The follow-up for malignant transformation and safety assessment will last 30 months from the end of treatment, for a total planned study duration of approximately 5.5 years. DISCUSSION: Restoring the activity of immune system through checkpoint inhibitor may play a crucial role against malignant transformation of OPMD by reverting the balance in favour of immune control and preventing cancer occurrence. TRIAL REGISTRATION: This trial was prospectively registered in ClinicalTrials.gov as NCT04504552 on 7th August 2020.
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Anticorpos Monoclonais Humanizados/administração & dosagem , Inibidores de Checkpoint Imunológico/administração & dosagem , Neoplasias Bucais/epidemiologia , Lesões Pré-Cancerosas/tratamento farmacológico , Evasão Tumoral/efeitos dos fármacos , Adulto , Anticorpos Monoclonais Humanizados/efeitos adversos , Antígeno B7-H1/antagonistas & inibidores , Ensaios Clínicos Fase II como Assunto , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Itália/epidemiologia , Perda de Heterozigosidade , Masculino , Neoplasias Bucais/genética , Neoplasias Bucais/imunologia , Neoplasias Bucais/prevenção & controle , Estudos Multicêntricos como Assunto , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/imunologia , Lesões Pré-Cancerosas/mortalidade , Recidiva , Evasão Tumoral/genética , Evasão Tumoral/imunologia , Adulto JovemAssuntos
Antineoplásicos Imunológicos , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Imunoterapia/métodos , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/terapia , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/terapia , Antineoplásicos Imunológicos/uso terapêutico , Tempo para o TratamentoRESUMO
PURPOSE OF REVIEW: Nonmelanoma skin cancers (NMSC) represent a heterogeneous group of diseases that encompasses among the principal histologies basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC), and Merkel cell carcinoma (MCC). Given the fact that high tumor mutational burden due to ultraviolet mutagenesis represents a common hallmark of NMSCs, immunotherapy has proved to be a promising therapeutic approach in recent years. The aim of this review is to shed light on immunotherapy applications in NMSCs in the curative setting. RECENT FINDINGS: Immune checkpoint inhibitors represent the first-line treatment of choice for advanced cSCC and MCC, while in second line for BCC. Given this success, more and more trials are evaluating the use of immune checkpoint blockade in neoadjuvant setting for NMSCs. Clinical trials are still ongoing, with the most mature data being found in cSCC. Also, translational studies have identified promising biomarkers of response. SUMMARY: Locoregional treatments of NMSCs can have non negligible functional and cosmetic impacts on patients, affecting their quality of life. As immunogenic diseases, neoadjuvant immunotherapy represents a promising treatment that could change the therapeutic path of these patients. Upcoming results from clinical trials will address these crucial issues.
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Carcinoma Basocelular , Carcinoma de Células Escamosas , Neoplasias Cutâneas , Humanos , Neoplasias Cutâneas/terapia , Neoplasias Cutâneas/patologia , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/patologia , Qualidade de Vida , Carcinoma Basocelular/terapia , Carcinoma Basocelular/patologia , Imunoterapia/métodosRESUMO
This systematic review and meta-analysis investigates the predictive and prognostic role of PD-L1 expression in treating head and neck squamous cell carcinoma (HNSCC). Recognizing the importance of PD-L1 in patient response to treatment, the main objective was to assess its impact on overall survival and progression-free survival in HNSCC patients. A thorough search of databases such as PubMed, Scopus, and Web of Science from 2010 to 2022, along with relevant articles and references, yielded 120 studies. Of these, 7 met the criteria focusing on HNSCC patients, PD-L1 expression evaluation, and treatment with PD-1 or PD-L1 inhibitors. Data extraction followed PRISMA guidelines and involved independent review and consensus for discrepancies. The primary outcomes analyzed were overall survival and progression-free survival in relation to PD-L1 expression levels in patients undergoing immunotherapy.Theseven randomized controlled trials selected had a total of 4,477 participants. Results showed that patients with positive PD-L1 expression experienced improved overall survival when treated with PD-1 or PD-L1 inhibitors, particularly those with high PD-L1 expression. However, PD-L1 expression did not significantly affect progression-free survival. These findings suggest that PD-L1 expression can be a predictive marker for better overall survival in HNSCC patients treated with immunotherapy. However, its influence on progression-free survival remains unclear, indicating the need for further research.
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Antígeno B7-H1 , Neoplasias de Cabeça e Pescoço , Humanos , Antígeno B7-H1/metabolismo , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Prognóstico , Biomarcadores Tumorais/metabolismo , Inibidores de Checkpoint Imunológico/uso terapêuticoRESUMO
Head and neck squamous cell carcinoma (HNSCC) is the seventh most commonly diagnosed cancer globally. HNSCC develops from the mucosa of the oral cavity, pharynx and larynx. Methylation levels of septin 9 (SEPT9) and short stature homeobox 2 (SHOX2) genes in circulating cellfree DNA (ccfDNA) are considered epigenetic biomarkers and have shown predictive value in preliminary reports in HNSCC. Liquid biopsy is a noninvasive procedure that collects tumorderived molecules, including ccfDNA. In the present study, a droplet digital PCR (ddPCR)based assay was developed to detect DNA methylation levels of circulating SEPT9 and SHOX2 in the plasma of patients with HNSCC. The assay was first set up using commercial methylated and unmethylated DNA. The dynamic changes in the methylation levels of SEPT9 and SHOX2 were then quantified in 20 patients with HNSCC during followup. The results highlighted: i) The ability of the ddPCRbased assay to detect very low copies of methylated molecules; ii) the significant decrease in SEPT9 and SHOX2 methylation levels in the plasma of patients with HNSCC at the first time points of followup with respect to T0; iii) a different trend of longitudinally DNA methylation variations in small groups of stratified patients. The absolute and precise quantification of SEPT9 and SHOX2 methylation levels in HNSCC may be useful for studies with translational potential.
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Carcinoma de Células Escamosas , Ácidos Nucleicos Livres , Neoplasias de Cabeça e Pescoço , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Metilação de DNA , Genes Homeobox , Carcinoma de Células Escamosas/patologia , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Reação em Cadeia da Polimerase , Proteínas do Citoesqueleto/genética , Ácidos Nucleicos Livres/genética , Neoplasias de Cabeça e Pescoço/genética , Biomarcadores Tumorais/metabolismoRESUMO
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.
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Neoplasias de Cabeça e Pescoço , Nivolumabe , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Nivolumabe/uso terapêutico , Platina , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/genética , BiomarcadoresRESUMO
Objectives: Benzydamine is a compound indicated in the treatment of symptoms of irritation/inflammation of the oropharyngeal cavity, including those associated with pain. Objectives of this expert opinion narrative review is to summarize current indicated benzydamine applications and elicit further ones to be explored. Materials and methods: In this expert opinion paper, evidences underlying the mechanism of action and clinical application of benzydamine are reviewed. Insights are also provided on possible new clinical applications of the drug and new formulations. Results: Current recognized indications of benzydamine include: relief of symptoms associated with inflammatory conditions of the mouth and oropharynx, symptomatic treatment of gingivitis and stomatitis, oral mucositis induced by chemotherapy and/or radiotherapy and post operative sore throat. In addition, among new applications that need to be explored experts embed: oral lichen planus, burning mouth syndrome, post intubation sore throat, antifungal action and new anticancer target agents induced mucositis. Conclusions: Benzydamine is a very versatile compound able to play an auxiliary and adjuvant role in the prevention and treatment of oral cavity/oropharynx disorders. According to experts' opinion there is the need to design clinical trials to highlight novel possible applications of benzydamine and implemented translational analyses to fine-tune patients' selection and open future research scenarios.
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The treatment of locally advanced (LA) Head and Neck Squamous Cell Carcinoma (HNSCC) is based on surgery followed by (chemo)radiation or on curative (chemo)radiation, depending on site and stage. Despite optimal locoregional treatment, about 50% of patients recur, with a huge impact on prognosis and substantial morbidity. The advent of immunotherapy (IT) with immune checkpoint inhibitors (ICIs) changed the paradigm of systemic treatment for recurrent/metastatic (RM) disease, showing activity, efficacy, and safety in both platinum-resistant and platinum-naïve patients. Such data led clinicians to design clinical trials to investigate early administration of IT even in the neoadjuvant or window of opportunity setting. In this review, we examine the published and ongoing trials investigating IT in the neoadjuvant setting for LA HNSCC. We address the current challenges of this treatment modality: optimal patient selection for neoadjuvant IT; choosing the appropriate systemic approach to enhance response without compromising tolerability; determining the ideal study endpoint, with a focus on major pathological response as a potential surrogate for overall survival; evaluating treatment response through imaging, considering the discordance between radiological and pathological assessments; and the influence of neoadjuvant IT response on locoregional treatment de-escalation strategies.
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Neoplasias de Cabeça e Pescoço , Terapia Neoadjuvante , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Quimioterapia de Indução , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Imunoterapia/métodosRESUMO
Adenoid cystic carcinoma (ACC) of salivary gland is a slowly growing tumor showing a propensity for delayed recurrence, with decreased survival rates. The identification of poor prognosis patients may help in defining molecular-based targeted strategies in this rare disease orphan of new treatments. Through a gene expression microarray-based approach followed by GSE functional analysis the expression profile of 46 primary untreated ACC samples and of ACC (h-TERT) tumor cells was analyzed. Patients who experienced early relapse showed enrichment in proliferation-related gene sets, including the G2-M checkpoint, E2F and myc targets, and in gene sets related to IFN signaling and aberrant proteostasis (FDR < 0.1), indicating increased mitotic and transcriptional activity in aggressive ACC. Similar functions were enriched in ACC samples classified by immunohistochemical staining as p63-negative, which exhibited increased protein burden and activation of pro-survival stress response pathways compared to p63-positive tumors. Compared to ACC tissues, ACC (h-TERT) cells share transcriptional features of aggressive p63-negative tumors. These data suggest association of specific pathway alterations with histopathological features of ACC, as recapitulated by p63 testing in patient prognostic stratification, anticipating new avenues for therapeutic intervention.
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Carcinoma Adenoide Cístico , Humanos , Carcinoma Adenoide Cístico/genética , Prognóstico , Proteostase , Agressão , Pontos de Checagem da Fase G2 do Ciclo CelularRESUMO
Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) are the most frequent cancers in humans, with cumulative ultraviolet radiation exposure, aging, and immunodepression as the main risk factors. In most cases, these malignancies arise in the head and neck area, and they can be treated with locoregional therapies. A minority of cases require systemic therapy. Currently, Sonic Hedgehog inhibitors (i.e., vismodegib and sonidegib) have been approved for advanced BCC, while the PD-1 checkpoint inhibitor cemiplimab has been approved as a first-line treatment for cSCC and as a second-line treatment for BCC. Nevertheless, there is a clinical need for an effective and safe systemic therapies for advanced synchronous (syn) BCC/cSCC not amenable to local treatments. International guidelines do not provide specific recommendations for patients affected by this condition, and no case reports on the full-dose association of these medications have been previously reported. Here, we present the cases of two elderly patients affected by synBCC/cSCC of the head and neck, who received combined therapy with cemiplimab and sonidegib at full dose and standard schedule, achieving remarkable clinical benefit and long-term responses, without major adverse events. The instance of a feasible treatment for patients with advanced synBCC/cSCC will become increasingly frequent with the advancement of life expectancy in the global population, and the synergistic activity of targeted therapies and immunotherapy-administered either in association or sequentially-deserves to be further explored.
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BACKGROUND: Sarcopenia is frequent in head and neck squamous cell carcinoma (HNSCC), as a consequence of malnutrition related to risk factors or tumoral mass. Treatment is associated with toxicities that lead to reduced calories intake and muscle mass wasting. Sarcopenia has been negatively associated with tumor control and survival outcomes. PURPOSE: Our aim is to evaluate the prognostic impact of sarcopenia on overall survival (OS) and progression free survival (PFS) in HNSCC patients undergoing chemoradiation therapy within a prospective clinical trial of chemoradiation vs induction chemotherapy followed by radiation and cetuximab (INTERCEPTOR). MATERIALS AND METHODS: On baseline CT or MRI, we investigated the association between OS and PFS with radiological markers of sarcopenia, measured at the third cervical vertebra level. We studied paravertebral skeletal muscles area (cm2), muscle density (HU), muscle index (cm2/m2), and intermuscular adipose tissue (IMAT) area (cm2). RESULTS: Imaging of 128 patients was evaluable. We found out that higher body mass index (BMI) was associated with better OS (p = 0.02), and PFS (p = 0.04). Skeletal muscle area (p = 0.02), and IMAT (p = 0.02) were negatively associated with PFS. IMAT was positively correlated with muscle area (Correlation coefficient 0.6, CI95% 0.47-0.7), and negatively associated with muscle density (Correlation coefficient -0.37, CI95% -0.53 - -0.18). CONCLUSIONS: IMAT can be used as predictor of PFS in HNC patients undergoing chemoradiation therapy. The amount of intermuscular fat deposits induces alterations of muscle quality, without alterations of muscle quantity, influencing patients' prognosis.
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Neoplasias de Cabeça e Pescoço , Sarcopenia , Humanos , Neoplasias de Cabeça e Pescoço/patologia , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/patologia , Prognóstico , Estudos Prospectivos , Sarcopenia/complicações , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologiaRESUMO
Despite the progress of surgery, radiotherapy, and neoadjuvant chemotherapy, the prognosis for advanced sinonasal cancers (SNCs) remains poor. In the era of precision medicine, more research has been conducted on the molecular pathways and recurrent mutations of SNCs, with the aim of understanding carcinogenesis, helping with diagnosis, identifying prognostic factors, and finding potentially targetable mutations. In the treatment of SNC, immunotherapy is rarely used, and no targeted therapies have been approved, partly because these tumors are usually excluded from major clinical trials. Data on the efficacy of targeted agents and immune checkpoint inhibitors are scarce. Despite those issues, a tumor-agnostic treatment approach based on targeted drugs against a detected genetic mutation is growing in several settings and cancer subtypes, and could also be proposed for SNCs. Our work aims to provide an overview of the main molecular pathways altered in the different epithelial subtypes of sinonasal and skull base tumors, focusing on the possible actionable mutations for which potential target therapies are already approved in other cancer types.
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Adenoid cystic carcinoma (ACC) is a rare malignancy characterized by high incidence of relapse. When relapsing, ACC has an indolent but relentless behaviour, thus leading to a poor long-term prognosis. The treatment of choice of relapsing ACC remains surgery followed by radiotherapy, whenever feasible. Therapeutic weapons are limited to systemic drugs. The most widely used chemotherapy regimen is the combination of cisplatin and doxorubicin, however with low response rate and not long lasting; there is also a lack of alternatives for second line therapies in case of disease progression. Therefore, a more comprehensive strategy aimed at identifying at preclinical level the most promising drugs or combination is clearly needed. In this study, the cytotoxic effects of two standard chemotherapy drugs, cisplatin and doxorubicin, and of five targeted therapy-drugs was tested in vitro, on an h-TERT immortalized ACC cell line, and in vivo, on zebrafish embryos with ACC tumoral cell xenograft. Then, combinations of one standard chemotherapy drug plus one targeted therapy drug were also evaluated, in order to find the best treatment strategy for ACC. Data obtained demonstrated that both vorinostat and olaparib significantly increased the standard chemotherapy cytotoxic effects, suggesting new interesting therapeutic options for ACC.
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Antineoplásicos , Carcinoma Adenoide Cístico , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Carcinoma Adenoide Cístico/tratamento farmacológico , Carcinoma Adenoide Cístico/patologia , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Peixe-ZebraRESUMO
OBJECTIVES: Adenoid cystic carcinoma (AdCC) is a rare disease, with indolent behavior and poor long-term survival. Many studies have evaluated the role of clinical and pathological factors at presentation on the risk of recurrence. In this study we investigated whether baseline demographic, clinical, and pathological characteristics at the time of primary curative treatment could influence the prognosis of patients once local and/or distant recurrence occurred. METHODS: All patients affected by primary salivary gland AdCC and treated with curative surgery from January 1997 to June 2016 were reviewed, evaluating those who later developed loco-regional recurrence and/or distant metastasis. Time from the first relapse to death (recurrent/metastatic overall survival, RMOS) was considered the outcome of interest. RESULTS: Out of 87 surgically treated AdCC patients, 36 relapsing lesions were included. Median ages at first presentation and recurrence were 55 and 60-year-old, respectively; 58% were females. Median disease-free-interval (DFI) was 22.0 months. Five-year RMOS was 47%. At univariate analysis, age ≥ 60-year-old (HR:2.67, p = 0.030), primary tumor lympho-vascular invasion (LVI) (HR:5.38, p = 0.003), adjuvant radiotherapy (RT) in the primary setting (HR:0.37, p = 0.043), and DFI < 30 months (HR:3.94, p = 0.008) significantly affected RMOS. Multivariable analysis confirmed the presence of LVI and shorter DFI as independent risk factors. CONCLUSIONS: Knowledge of baseline clinicopathological features is helpful in the prognostic stratification of patients with recurrent AdCC, with LVI as the most relevant baseline factor. Adjuvant RT demonstrated its protective role on survival even once recurrence occurred, further supporting its adoption in the primary setting.
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Carcinoma Adenoide Cístico , Neoplasias das Glândulas Salivares , Carcinoma Adenoide Cístico/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Prognóstico , Estudos Retrospectivos , Neoplasias das Glândulas Salivares/patologia , Glândulas Salivares/patologia , Taxa de SobrevidaRESUMO
Background: Oral potentially malignant disorders (OPMDs) represent a heterogeneous set of different histological lesions, characterized by the capacity to transform in oral squamous cell carcinoma (OSCC). Despite optimal surgical treatment, approximately 20%-30% of OPMDs may evolve into OSCC. No clear clinical/histological factors are able to identify OPMDs at higher risk of malignant transformation. Materials and Methods: We considered surgically treated patients with a diagnosis of OPMDs, enrolled from 1996 to 2019 at ASST Spedali Civili of Brescia without a diagnosis of OSCC within the previous 2 years. Clinical and histological characteristics were recorded. Outcomes of interest were recurrence-free survival (RFS), defined as the time from surgery for primary OPMD to any relapse of OPMD or malignant transformation, whichever occurred first, and carcinoma-free survival (CFS), defined as the time from surgery for OPMD to malignant transformation. Results: We retrospectively reviewed 106 OPMDs cases. Median age at first diagnosis was 64 years old (IQR = 18.75); female patients comprise 51.9% of the cases. During a median follow-up of 30.5 months (IQR = 44), in 23.5% of patients, malignant transformation occurred. RFS at 1, 5, and 10 years was 92.4%, 60.9%, and 43.2%, respectively. Female sex and history of previous OSCC were independent risk factors for RFS. CFS at 1, 5, and 10 years of follow-up was 97.1%, 75.9%, and 64.4%, respectively. Previous OSCC was an independent risk factor for CFS. Conclusions: In this large series of OPMDs, only previous diagnosis of OSCC was a prognostic factor for further OSCC occurrence. Given the lack of additional clinical/pathological prognostic factors, we advocate further studies into molecular characterization of OPMDs to better stratify the risk of malignant transformation.
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Myeloid growth factors, either granulocyte colony-stimulating factor (CSF) or granulocyte-macrophage CSF, are widely used to reduce the incidence and severity of chemotherapy-induced neutropenia by prophylactic or therapeutic administration. However, their activity in the novel therapeutic regimens, which often rely on the association between immunotherapy and chemotherapy, has not been thoroughly characterized yet. This paper presents some of the preclinical and clinical research regarding the putative interplay between myeloid growth factors and the immune system, advocating further studies to elucidate their potential positive or negative consequences on the outcomes when administered with immunotherapeutic agents.
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Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Fator Estimulador de Colônias de Granulócitos/farmacologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Imunoterapia/métodos , Neoplasias/terapia , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Humanos , Inibidores de Checkpoint Imunológico/administração & dosagem , Neoplasias/sangue , Neoplasias/tratamento farmacológico , Neutropenia/induzido quimicamente , Neutropenia/tratamento farmacológico , Neutropenia/prevenção & controleRESUMO
Intrathyroidal thymic carcinoma (ITC) is a rare thyroid tumor that resembles thymic carcinoma, for which there are no recommendations on diagnostic and therapeutic approaches. We performed a pooled analysis of published ITC cases to describe the natural history of this disease and identify prognostic factors. We performed a systematic review of histopathological-confirmed ITC cases published in the literature in English. The following keywords were used: 'intrathyroidal thymic carcinoma', 'carcinoma showing thymus-like differentiation', 'CASTLE tumor', 'thyroid carcinoma showing thymus like differentiation'. Fifty eligible publications were identified, providing data from 132 patients, plus a case diagnosed at our institution. Median disease-free survival (DFS) of this patient series was 144 months (range 91-197), while median overall survival (OS) was not reached. Upfront surgery was performed in 97% of patients and 24% of them experienced disease recurrence after a median of 19 months (range 13-25). Complaining of major symptoms, as a sign of more advanced local stage, was the only prognostic factor significantly associated with a higher risk of death at multivariate analysis (HR 4.903, 95% CI: 1.092-22.008, P = 0.038). Postoperative radiation therapy was not associated with prognosis, while not enough data were available to assess the efficacy of chemotherapy. ITC is a rather indolent disease and ITC patients have a relatively good prognosis. Surgery is the mainstay of therapy. Survival outcome of patients depends on tumor burden and complete surgical resection. Postoperative radiation effect seems to be negligible. Data on the efficacy of chemotherapy in advanced patients are lacking.