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PURPOSE: To identify response predictors in patients with head and neck squamous cell carcinoma (N + HNSCC) and persistent lymph nodes after curative chemoradiotherapy treatment (CCRT). MATERIALS AND METHODS: Consecutive patients with N + HNSCC treated with CCRT and persistent lymph nodes at first follow-up between 2015 and 2021 were identified and analyzed. Complete response was defined as the absence of lymph node metastatic involvement in patients with salvage lymphadenectomy or the absence of progression after 1 year of successive follow-ups. Tumour type and location, staging, and human papillomavirus (HPV) status were considered for analysis. The number and size of lymph nodes, type, shape, enhancement and margins on diagnostic and follow-up CT were also analyzed. RESULTS: The cohort included 46 patients with 134 pathological lymph nodes. Logistic regression models showed the following variables to be significant: performance of salvage lymphadenectomy (OR 0.094, [CI 95% 0.004-0.61], p = 0.037); the type of lymphadenopathy on diagnostic CE-CT (solid vs. cystic) (N1: OR = 4.11, [CI 95% 1.11-17.93], p = 0.042 and N3: OR 6.42, [CI 95% 1.2-42.56], p = 0.036); the change of shape (round to oval) on the follow-up CE-CT (OR 9.76, [CI 95% 1.79-8.57], p = 0.016) and the time in days between CCRT and the first follow-up CE-CT (OR 1.06, [CI 95% 1.004-1.13], p = 0.048). CONCLUSIONS: In our experience, the presence of solid lymph nodes on pre-treatment CT and the change in shape from round to oval on post-treatment CT are predictors of response to treatment in patients with N + HNSCC persistent lymph nodes after CCRT. Increasing the temporal interval between treatment and follow-up CT should be considered to avoid unnecessary nodal dissections.
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Neoplasias de Cabeça e Pescoço , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico por imagem , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/terapia , Neoplasias de Cabeça e Pescoço/patologia , Linfonodos/patologia , Indução de Remissão , QuimiorradioterapiaRESUMO
PURPOSE OF REVIEW: We review the new systemic treatment strategies for differentiated thyroid carcinoma, as well as the acquaintance of its molecular biology. RECENT FINDINGS: Multiple kinase inhibitor drugs have become the standard therapy for thyroid cancer, albeit several adverse effects. In the last few years, new molecules have raised with an overall safety profile. Most of them, are considered targeted therapies directed toward driven-molecules alterations, such as neurotrophic tyrosine kinase receptor (NTRK) inhibitors for NTRK-fusion thyroid cancer and rearranged during transfection (RET) inhibitors for RET-fusion thyroid cancer. Recently, promising outcomes and safety data have been presented. Furthermore, other novel strategies for advanced thyroid carcinoma are currently investigated in clinical trials.The ability to provide precision medicine to patients in routine clinical settings depends on the availability of molecular profiling test at their cancer centers. The impossibility to perform molecular characterization could turn out to be a diagnostic and treatment limitation for some patients. SUMMARY: The treatment of advanced differentiated thyroid carcinoma has undergone rapid evolution in the last decade. An emerging treatment era is coming. From now to then, we will need to face the different types of diagnostic tools for molecular characterization, their interpretation and, finally the access to targeted therapies.
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Inibidores de Proteínas Quinases/uso terapêutico , Neoplasias da Glândula Tireoide/tratamento farmacológico , Diferenciação Celular/fisiologia , Ensaios Clínicos Fase I como Assunto , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Humanos , Terapia de Alvo Molecular , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologiaRESUMO
Although cetuximab plus radiotherapy is a standard treatment for patients with inoperable head and neck squamous cell carcinoma (HNSCC), its efficacy varies greatly among individuals. To identify predictive markers of efficacy, we examined the effects of single nucleotide polymorphisms (SNPs) in hypoxia-related and DNA repair genes on the clinical outcome and occurrence of skin toxicity. We analyzed 61 consecutive patients with HNSCC for the presence of specific SNPs (HIF-1α, HIF-2α, HIF-1ß, VHL, FIH-1, XRCC1, and XRCC5). The results were then correlated with time to progression (TTP), overall survival (OS), and toxicity (epithelitis, mucositis, and folliculitis). The median TTP and OS were better in patients with severe vs mild mucositis (17 vs 7 months, p = 0.03; and 26 vs 12 months, p = 0.016, respectively) and folliculitis (10 vs 7 months, p = 0.01, and 26 vs 10 months, p < 0.001, respectively). Patients with the HIF-1α CT/TT genotype had better OS than those with the wild-type HIF-1α CC genotype (28 vs 13 months, p = 0.035). Patients with the XRCC5 GG/AA genotype had longer TTP than patients with the XRCC5 AG genotype (11 vs 7 months, p = 0.035). Severe skin toxicity and SNPs of HIF-1α and XRCC5 were associated with different outcomes among patients treated with radiotherapy plus cetuximab.
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Alelos , Antineoplásicos/uso terapêutico , Carcinoma de Células Escamosas , Cetuximab/uso terapêutico , Quimiorradioterapia/métodos , Reparo do DNA , Neoplasias de Cabeça e Pescoço , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Análise de Variância , Antineoplásicos/efeitos adversos , Translocador Nuclear Receptor Aril Hidrocarboneto/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Cetuximab/efeitos adversos , Quimiorradioterapia/efeitos adversos , Proteínas de Ligação a DNA/genética , Feminino , Foliculite/genética , Genótipo , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Hipóxia , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Autoantígeno Ku/genética , Masculino , Pessoa de Meia-Idade , Oxigenases de Função Mista/genética , Mucosite/genética , Proteínas Repressoras/genética , Resultado do Tratamento , Proteína Supressora de Tumor Von Hippel-Lindau/genética , Proteína 1 Complementadora Cruzada de Reparo de Raio-XRESUMO
BACKGROUND: Patients with recurrent or metastatic squamous-cell carcinoma of the head and neck (HNSCC) progressing after first-line platinum regimens have a poor prognosis and few treatment options. Afatinib, an irreversible ERBB family blocker, has shown efficacy in a phase 2 study in this setting. We aimed to assess the efficacy and safety of afatinib compared with methotrexate as second-line treatment in patients with recurrent or metastatic HNSCC progressing on or after platinum-based therapy. METHODS: In this open-label, phase 3, randomised controlled trial conducted in 101 centres in 19 countries, we enrolled patients aged 18 years or older with histologically or cytologically confirmed HNSCC that was recurrent, metastatic, or both who had progressed on or after first-line platinum-based therapy, were not amenable for salvage surgery or radiotherapy, and who had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Previous treatment with more than one systemic regimen in this setting was not allowed; previous treatment with EGFR-targeted antibody therapy (but not EGFR-targeted tyrosine-kinase inhibitors) was allowed. We randomly assigned eligible patients in a 2:1 ratio to receive oral afatinib (40 mg/day) or intravenous methotrexate (40 mg/m(2) per week), stratified by ECOG performance status and previous EGFR-targeted antibody therapy for recurrent or metastatic disease. Randomisation was done centrally with an interactive voice or web-based response system. Clinicians and patients were not masked to treatment allocation; independent review of tumour response was done in a blinded manner. The primary endpoint was progression-free survival as assessed by an independent, central imaging review committee. Efficacy analyses were done in the intention-to-treat population and safety analyses were done in patients who received at least one dose of study drug. This ongoing study is registered with ClinicalTrials.gov, number NCT01345682. FINDINGS: Between Jan 10, 2012, and Dec 12, 2013, we enrolled 483 patients and randomly assigned 322 to afatinib and 161 to methotrexate. After a median follow-up of 6·7 months (IQR 3·1-9·0), progression-free survival was longer in the afatinib group than in the methotrexate group (median 2·6 months [95% CI 2·0-2·7] for the afatinib group vs 1·7 months [1·5-2·4] for the methotrexate group; hazard ratio [HR] 0·80 [95% CI 0·65-0·98], p=0·030). The most frequent grade 3 or 4 drug-related adverse events were rash or acne (31 [10%] of 320 patients in the afatinib group vs none of 160 patients in the methotrexate group), diarrhoea (30 [9%] vs three [2%]), stomatitis (20 [6%] vs 13 [8%]), fatigue (18 [6%] vs five [3%]), and neutropenia (1 [<1%] vs 11 [7%]); serious adverse events occurred in 44 (14%) of afatinib-treated patients and 18 (11%) of methotrexate-treated patients. INTERPRETATION: Afatinib was associated with significant improvements in progression-free survival and had a manageable safety profile. These findings provide important new insights into the treatment of this patient population and support further investigations with irreversible ERBB family blockers in HNSCC. FUNDING: Boehringer Ingelheim.
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Metotrexato/administração & dosagem , Recidiva Local de Neoplasia/tratamento farmacológico , Quinazolinas/administração & dosagem , Adulto , Afatinib , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia/patologia , Platina/administração & dosagem , Carcinoma de Células Escamosas de Cabeça e Pescoço , Resultado do TratamentoRESUMO
BACKGROUND: To evaluate the importance of larynx compartments in the prognosis of T3-T4a laryngeal cancer treated with transoral laser microsurgery. METHODS: Two hundred and two consecutive pT3-T4a larynx carcinomas. Pre-epiglottic space involvement, anterior and posterior paraglottic space (PGS) involvement, vocal cord, and arytenoid mobility were determined. Local control with laser (LC), overall survival (OS), disease-specific survival (DSS), and laryngectomy-free survival (LFS) were evaluated. RESULTS: The lowest LC was found in tumors with fixed arytenoid. In the multivariate analysis, positive margins (hazard ratio [HR] = 0.289 [0.085-0.979]) and anterior (HR = 0.278 [0.128-0.605]) and posterior (HR = 0.269 [0.115-0.630]) PGS invasion were independent factors of a reduced LC. Anterior (HR = 3.613 [1.537-8.495]) and posterior (HR = 5.195 [2.167-12.455]) PGS involvement were independent factors of total laryngectomy. Five-year OS, DSS, and LFS rates were 63.9%, 77.5%, and 77.5%, respectively. Patients with posterior PGS presented a reduced 5-year LFS. CONCLUSIONS: Tumor classification according to laryngeal compartmentalization depicts strong correlation with LC and LFS.
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Neoplasias Laríngeas , Terapia a Laser , Intervalo Livre de Doença , Glote/patologia , Humanos , Neoplasias Laríngeas/patologia , Neoplasias Laríngeas/cirurgia , Laringectomia , Microcirurgia , Estadiamento de Neoplasias , Prognóstico , Estudos RetrospectivosRESUMO
Recurrent respiratory papillomatosis (RRP) is a chronic disease caused by human papillomavirus (HPV). RRP is a clinical challenge because of the high recurrence rate, poor surgery response, extension to tracheobronchial tree and because of the risk of malignancy in some cases. There is no consensus on which adjuvant therapy is better for those patients with highly recurrent course. Because papilloma cells overexpress the epidermal growth factor receptor (EGFR), together with an increased expression of COX-2 and prostaglandin E2, the combination of erlotinib and celecoxib seems plausible, and could be proposed for patients with poor response to previous lines of treatment.
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Antineoplásicos/uso terapêutico , Celecoxib/uso terapêutico , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Cloridrato de Erlotinib/uso terapêutico , Infecções por Papillomavirus/tratamento farmacológico , Infecções Respiratórias/tratamento farmacológico , Adolescente , Criança , Pré-Escolar , Terapia Combinada , Feminino , Humanos , Infecções por Papillomavirus/cirurgia , Infecções Respiratórias/cirurgia , Retratamento , Adulto JovemRESUMO
BACKGROUND: Indications of transoral laser microsurgery (TLM) are conditioned by the risk of local relapse. OBJECTIVE: To evaluate prognostic factors of local relapse and local control with TLM (LC-TLM). METHODS: Local relapse and LC-TLM were evaluated in 1119 patients. Logistic regression and CHAID decision tree analysis were performed. RESULTS: Local relapse correlated to previous radiotherapy failure (8.45, CI 95%: 2.64-27.03; P < .001), paraglottic involvement (2.42, CI: 1.41-4.15; P = .001), anterior commissure involvement (2.12, CI: 1.43-3.14; P < .001), grade of differentiation (1.74, CI: 1.18-2.57; P = .005), and alcohol consumption (1.4, CI: 0.99-1.98; P = .057). Local relapse tended to inversely correlate with experience (0.73, CI: 0.51-1.03; P = .078). The most important factors for local relapse were previous radiotherapy failure and anterior commissure involvement. LC-TLM inversely correlated with previous radiotherapy failure (0.09, CI: 0.03-0.28; P < .001), paraglottic involvement (0.25, CI: 0.14-0.43; P < .001), anterior commissure involvement (0.49, CI: 0.32-0.77; P = .007), margins (0.56, CI: 0.30-1.04; P = .068), and differentiation (0.68, CI: 0.44-1.05; P = .087). LC-TLM correlated with experience (1.71, CI: 1.13-2.55; P = .010). The most important factors for LC-TLM were previous radiotherapy failure and paraglottic involvement. CONCLUSION: Previous radiotherapy failure is the most important factor for local relapse and LC-TLM. In primary treatments, anterior commissure involvement and paraglottic involvement are the most important factors for local relapse and LC-TLM, respectively.
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Carcinoma/cirurgia , Neoplasias Laríngeas/cirurgia , Terapia a Laser , Microcirurgia , Recidiva Local de Neoplasia/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma/patologia , Carcinoma/radioterapia , Árvores de Decisões , Feminino , Humanos , Neoplasias Laríngeas/patologia , Neoplasias Laríngeas/radioterapia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Preservação de Órgãos , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Adulto JovemRESUMO
Administration of external beam radiotherapy (EBRT) for a bulky recurrence or primary bulky tumor of differentiated thyroid carcinoma (DTC) is rare. No previous experience is available on the feasibility of administering EBRT simultaneously with systemic treatment with doxorubicin or sorafenib, or both. The present case study reported the results from two different institutions on 5 consecutive patients. Side effects and tolerance to radiotherapy plus systemic treatment with doxorubicin (20 mg/m2 intravenously weekly for 6/8 consecutive weeks) or sorafenib (400 mg/12 h orally for 8 weeks) or both, were analyzed in patients with DTC. The local response to radiotherapy and patient outcome was also analyzed. A total of 4 males and 1 female, aged 37-62 years with cervical bulky mass DTC were included. The pathological tumor types were papillary (2 patients), follicular (2 patients) and medullar thyroid carcinoma (1 patient). The radiated cervical mass was local recurrence in 3 cases and primary tumor in the other two. The total dose of radiotherapy ranged between 50 and 64.8 Gy. Three patients received sorafenib, 1 patient received doxorubicin and 1 patient received both treatments. The total planned dose of radiotherapy was administered to all patients. Grade 2 anemia and erythrodysesthesia was the most frequent toxicity. Only the patient who received doxorubicin plus sorafenib had grade 3 toxicity consisting of lymphopenia, folliculitis and mucositis. All but 1 patient had a good local response to radiotherapy. The administration of EBRT concurrently with sorafenib and doxorubicin to patients with DTC with a bulky cervical mass is feasible.
RESUMO
OBJECTIVES: In the EXTREME trial, a combination of cisplatin or carboplatin plus 5-fluorouracil (5-FU) and cetuximab was superior to cisplatin/carboplatin plus 5-FU for first-line treatment of recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). With the aim of improving fluoropyrimidine-related tolerance without decreasing its efficacy, the safety and efficacy of carboplatin plus the oral fluoropyrimidine tegafur and cetuximab were investigated. METHODS: A retrospective analysis of 104 patients with recurrent or metastatic HNSCC was conducted. Patients were treated with carboplatin (area under the curve: 5 mg/mL/min) on day 1, oral tegafur (250 mg/m2 twice daily) for 21 consecutive days, and cetuximab (400 mg/m2 as an initial 2-hour intravenous infusion, then 250 mg/m2 as a 1-hour weekly infusion for 3 weeks) for ≤6 cycles. Patients who responded to the therapy then received weekly cetuximab maintenance therapy. RESULTS: Treatment was well tolerated with a high level of compliance (relative dose intensity: 96%, 88%, and 81% for carboplatin, tegafur, and cetuximab, respectively). Grade 3-4 adverse events (AEs) were observed in 38% of patients (skin reactions in 17% of patients, anemia 4%, and neutropenia 3%). Grade 1-2 AEs included skin reactions (52% of patients), hypomagnesemia (20%), asthenia (19%), and anemia (13%). No venous thrombosis related to chemotherapy perfusion was observed. Over a median follow-up of 21 months, the median overall and progression-free survival were 11 and 6 months, respectively, and the overall response rate was 35%. CONCLUSIONS: Carboplatin plus oral tegafur and cetuximab is a safe, well-tolerated first-line therapy for recurrent or metastatic HNSCC.
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Carcinoma de Células Escamosas/tratamento farmacológico , Fluoruracila/administração & dosagem , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Idoso , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/mortalidade , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Imunossupressores/administração & dosagem , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Espanha/epidemiologia , Carcinoma de Células Escamosas de Cabeça e Pescoço , Taxa de Sobrevida/tendências , Resultado do TratamentoRESUMO
OBJECTIVE: To evaluate serum vascular endothelial growth factor (VEGF) as a prognostic factor in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck treated with metronomic (weekly) paclitaxel. DESIGN: Before-and-after trial. PATIENTS: A total of 33 consecutive patients were enrolled. Patients with recurrent and/or metastatic cancer of the head and neck refractory to platinum-based chemotherapy met inclusion criteria. SETTING: Tertiary referral center. INTERVENTION: Patients were treated weekly with 80 mg/m(2) of paclitaxel for 6 weeks. MAIN OUTCOME MEASURES: Blood samples were collected after each dose and analyzed for serum VEGF using enzyme-linked immunosorbent assay kits. Nonparametric tests were used to analyze serum VEGF levels. RESULTS: In 33 patients, complete response was achieved in 1 (3%) and partial response in 20 (61%). No differences were found between responders and nonresponders with different levels of serum VEGF at any of the measurement times (baseline, after the first dose, and after the sixth dose). In responders, the median level of serum VEGF decreased after the first dose compared with baseline, but by the sixth dose, the median serum VEGF level had returned to baseline levels in all groups. The intensity of the serum VEGF level decrease (simple decrease, a decrease of at least 30%, or a decrease of at least 70%) was not related to response. The progression-to-disease time increased in the patients with a serum VEGF level reduction of at least 30% (P = .01) after 6 doses and decreased in patients with initially high levels, which remained high after the sixth dose (P = .03). CONCLUSIONS: Serum VEGF levels after the first dose of paclitaxel may predict response to weekly paclitaxel in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck. Initially high serum VEGF levels that persist after the sixth dose predict a shorter period until tumor progression.
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Antineoplásicos Fitogênicos/administração & dosagem , Neoplasias de Cabeça e Pescoço/sangue , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Paclitaxel/administração & dosagem , Fator A de Crescimento do Endotélio Vascular/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Relação Dose-Resposta a Droga , Esquema de Medicação , Estudos de Viabilidade , Feminino , Seguimentos , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Resultado do TratamentoRESUMO
Sinonasal tumors are rare neoplasms with distinctive clinical, aetiological and pathological features. The diagnosis and treatment of these tumours is challenging because of their low incidence, histological diversity and production of non-specific symptoms in the early stages. They have a variable prognosis depending on their histology, origin and staging. Their location, close to neurocritical structures, which are of special relevance to surgery and postoperative treatment, makes their treatment difficult and complex, leading to high morbidity and mortality. Surgery followed by radiotherapy is the mainstay of treatment. To provide the best possible care, patients with sinonasal cancer should be treated in clinical referral centres specializing in skull-base pathologies. Such centres should include a multidisciplinary team led by otolaryngologist surgeons. This article outlines a consensus protocol for the management of these tumours devised by the Spanish Society of Otolaryngology in collaboration with the Spanish Society of Medical Oncology and the Spanish Society for Radiation Oncology.
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Neoplasias dos Seios Paranasais/diagnóstico , Neoplasias dos Seios Paranasais/terapia , Árvores de Decisões , HumanosRESUMO
BACKGROUND: Axitinib, an antiangiogenic multikinase inhibitor (MKI), was evaluated in the compassionate use programme (CUP) in Spain (October 2012-November 2014). SUBJECTS AND METHODS: 47 patients with advanced radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC, n = 34) or medullary thyroid cancer (MTC, n = 13) with documented disease progression were treated with axitinib 5 mg b.i.d. The primary efficacy endpoint was objective response rate (ORR) by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. Progression-free survival (PFS) and adverse events (AEs) were secondary objectives. Regulatory authorities validated the CUP, and all patients signed informed consent form. RESULTS: Axitinib was administered as first-line therapy in 17 patients (36.2%), as second-line in 18 patients (38.3%) and as third/fourth-line in 12 patients (25.5%). With a median follow-up of 11.5 months (0-24.3), ORR was 27.7% (DTC: 29.4% and MTC: 23.1%) and median PFS was 8.1 months (95% CI: 4.1-12.2) (DTC: 7.4 months (95% CI: 3.1-11.8) and MTC: 9.4 months (95% CI: 4.8-13.9)). Better outcomes were reported with first-line axitinib, with an ORR of 53% and a median PFS of 13.6 months compared with 16.7% and 10.6 months as second-line treatment. Twelve (25.5%) patients required dose reduction to 3 mg b.i.d. All-grade AEs included asthenia (53.2%), diarrhoea (36.2%), hypertension (31.9%) and mucositis (29.8%); grade 3/4 AEs included anorexia (6.4%), diarrhoea (4.3%) and cardiac toxicity (4.3%). CONCLUSION: Axitinib had a tolerable safety profile and clinically meaningful activity in refractory and progressive thyroid cancer regardless of histology as first-line therapy. To our knowledge, this is the first time that cross-resistance between MKIs is suggested in thyroid cancer, highlighting the importance of prospective sequential clinical studies.
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Imidazóis/uso terapêutico , Indazóis/uso terapêutico , Radioisótopos do Iodo , Inibidores de Proteínas Quinases/uso terapêutico , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Axitinibe , Carcinoma Neuroendócrino/diagnóstico por imagem , Carcinoma Neuroendócrino/tratamento farmacológico , Carcinoma Neuroendócrino/epidemiologia , Feminino , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Estudos Retrospectivos , Espanha/epidemiologia , Neoplasias da Glândula Tireoide/epidemiologia , Resultado do TratamentoRESUMO
INTRODUCTION: Local progression of papillary thyroid carcinoma (PTC) after failure of standard therapies may cause pain, ulceration, and bleeding. As patients are fully aware of the tumor growth, they might suffer high grade anxiety. Electrochemotherapy (ECT) is a new local palliative treatment for skin metastases of malignant melanoma or other tumors, including squamous head e neck cancer patients. OBJECTIVE: To evaluate the impact of ECT in patients with local progression of PTC. METHODS: Four patients with local progression of PTC were treated with ECT based on Bleomycin, and evaluated according to tumor response, local pain and side effects. RESULTS: In all cases, some grade of tumor response was observed, lasting 6, 7, 12 and 8 months, respectively. Also, reduction of local pain and anxiety was registered in all patients. Tumor infiltrated skin necrosis was the only collateral effect of the treatment. ECT induced a tumor response in all PTC patients with improvement of symptoms. CONCLUSIONS: ECT may be an option for local palliative treatment in PTC patients with local tumor progression.
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Antibióticos Antineoplásicos/administração & dosagem , Bleomicina/administração & dosagem , Carcinoma/tratamento farmacológico , Eletroquimioterapia , Cuidados Paliativos , Neoplasias da Glândula Tireoide/tratamento farmacológico , Carcinoma Papilar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Câncer Papilífero da Tireoide , Resultado do TratamentoRESUMO
BACKGROUND: Controversy exists regarding treatment of advanced laryngeal cancer. The purpose of this study was to evaluate the oncologic and functional outcomes of T3 to T4a supraglottic squamous carcinomas treated with transoral laser microsurgery (TLM). METHODS: We conducted a retrospective analysis from an SPSS database. Primary outcomes were: locoregional control, overall survival (OS), disease-specific survival (DSS), laryngectomy-free survival, and function-preservation rates. Secondary objectives were: rate of tracheostomies and gastrostomies according to age. Risk factors for local control and larynx preservation were also evaluated. RESULTS: One hundred fifty-four consecutive patients were chosen for this study. Median follow-up was 40.7 + /- 32.8 months. Five and 10-year OS, DSS, and laryngectomy-free survival were 55.6% and 47%, 67.6% and 58.6%, and 75.2% and 59.5%, respectively. Paraglottic involvement was an independent factor for larynx preservation. Six patients (3.9%) needed a definitive tracheostomy, a gastrostomy, or both. The gastrostomy rate was higher in the group of patients above 65 years of age (p = .03). Five-year laryngectomy-free survival with preserved function was 74.5%. CONCLUSION: TLM constitutes a true alternative for organ preservation in locally advanced supraglottic carcinomas with good oncologic and functional outcomes. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1050-1057, 2016.
Assuntos
Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/cirurgia , Neoplasias Laríngeas/patologia , Neoplasias Laríngeas/cirurgia , Terapia a Laser/métodos , Microcirurgia/métodos , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/mortalidade , Distribuição de Qui-Quadrado , Bases de Dados Factuais , Intervalo Livre de Doença , Feminino , Glote/patologia , Glote/cirurgia , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Estimativa de Kaplan-Meier , Neoplasias Laríngeas/mortalidade , Laringectomia/métodos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Cirurgia Endoscópica por Orifício Natural/métodos , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Medição de Risco , Carcinoma de Células Escamosas de Cabeça e Pescoço , Análise de Sobrevida , Resultado do TratamentoRESUMO
A combination of cisplatin and 5-fluorouracil (PF) is considered the standard induction chemotherapy regimen for squamous cell carcinoma of the head and neck (SCCHN). The present study compares the efficacy and safety of a new combination of cisplatin/docetaxel versus the PF regimen. A total of 83 chemotherapy-naive patients with locally advanced SCCHN were randomised to receive every 21 d (i) docetaxel 85 mg/m2 i.v. on day 1 and cisplatin 40 mg/m2 i.v. on days 1 and 2 (arm A) or (ii) cisplatin 100 mg/m2 i.v. on day 1 followed by 5-fluorouracil 1000 mg/m2 in 24 h continuous infusion for 5 d (arm B). A total of 287 cycles (range 1-3 per patient) were administered. Among 76 patients evaluable for response, the overall response rate in arm A was 70% (complete response (CR) 26%, partial response (PR) 44%) and in arm B 69% (CR 16%, PR 54%), respectively. Median survival in arm A was 7.6 months (95% CI: 5.8-11.1) and 9.9 months (95% CI: 7.4-14.6) for arm B. The most frequent grade 3/4 toxicity in arm A was neutropaenia (34.1%) and diarrhoea (9.8%) versus mucositis (29.3%) and neutropaenia (19.5%) in arm B. Both schedules present a similar efficacy, with different but acceptable toxicity patterns.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Docetaxel , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Análise de Sobrevida , Taxoides/administração & dosagem , Taxoides/efeitos adversos , Resultado do TratamentoRESUMO
Although thyroid cancer usually has an excellent prognosis, few therapeutic options are available in the refractory setting. Based on the recent results of phase II studies with tyrosine kinase inhibitors, we designed a retrospective analysis of patients with metastatic thyroid cancer treated with sorafenib in seven Spanish referral centers. Consecutive patients with progressive metastatic thyroid cancer (papillary, follicular, medullary, and anaplastic) not suitable for curative surgery, radioactive-iodine therapy, or radiotherapy were treated with sorafenib 400 mg twice a day. The primary end point was objective response rate (RR). Secondary end points included toxicity, median progression-free survival (mPFS), median overall survival (mOS), and correlation between tumor marker levels (thyroglobulin, calcitonin, and carcinoembryonic antigen) and efficacy. Between June 2006 and January 2010, 34 patients were included in the study. Sixteen patients presented differentiated thyroid carcinomas (DTC) of which seven (21%) were papillary, nine (26%) follicular, 15 (44%) medullary (MTC), and three (9%) were anaplastic (ATC). Eleven (32%) patients achieved partial response and 14 (41%) had stable disease beyond 6 months. Regarding histological subtype, RRs were 47% (seven of 15) for MTC, 19% (three of 16) for DTC, and 33% (one of three) for ATC. With a median follow-up of 11.5 months, mPFS were 13.5, 10.5, and 4.4 months for DTC, MTC, and ATC respectively. Tumor markers were evaluated in 22 patients, and a statistically significant association was observed between RR and decrease in tumor marker levels >50% (P=0.033). In this retrospective trial, sorafenib showed antitumor efficacy in all histological subtypes of thyroid cancer, warranting further development in this setting.
Assuntos
Antineoplásicos/uso terapêutico , Benzenossulfonatos/uso terapêutico , Piridinas/uso terapêutico , Neoplasias da Glândula Tireoide/tratamento farmacológico , Adulto , Calcitonina/sangue , Antígeno Carcinoembrionário/sangue , Intervalo Livre de Doença , Humanos , Estimativa de Kaplan-Meier , Estudos Longitudinais , Metástase Neoplásica , Niacinamida/análogos & derivados , Compostos de Fenilureia , Estudos Retrospectivos , Sorafenibe , Tireoglobulina/sangue , Neoplasias da Glândula Tireoide/sangue , Neoplasias da Glândula Tireoide/patologiaAssuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Nasofaríngeas/tratamento farmacológico , Adenocarcinoma/patologia , Adenocarcinoma/radioterapia , Administração Metronômica , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carboplatina/administração & dosagem , Terapia Combinada , Epistaxe/etiologia , Feminino , Humanos , Pessoa de Meia-Idade , Obstrução Nasal/etiologia , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/radioterapia , Invasividade Neoplásica , Tegafur/administração & dosagemRESUMO
ABSTRACT INTRODUCTION: Local progression of papillary thyroid carcinoma (PTC) after failure of standard therapies may cause pain, ulceration, and bleeding. As patients are fully aware of the tumor growth, they might suffer high grade anxiety. Electrochemotherapy (ECT) is a new local palliative treatment for skin metastases of malignant melanoma or other tumors, including squamous head e neck cancer patients. OBJECTIVE: To evaluate the impact of ECT in patients with local progression of PTC. METHODS: Four patients with local progression of PTC were treated with ECT based on Bleomycin, and evaluated according to tumor response, local pain and side effects. RESULTS: In all cases, some grade of tumor response was observed, lasting 6, 7, 12 and 8 months, respectively. Also, reduction of local pain and anxiety was registered in all patients. Tumor infiltrated skin necrosis was the only collateral effect of the treatment. ECT induced a tumor response in all PTC patients with improvement of symptoms. CONCLUSIONS: ECT may be an option for local palliative treatment in PTC patients with local tumor progression.
Resumo Introdução: A progressão local do carcinoma papilífero de tireoide (CPT) após a falha da terapia de rotina pode causar dor, ulceração e sangramento. Considerando que os pacientes estão perfeitamente cientes do crescimento tumoral, podem apresentar um alto grau de ansiedade. A eletroquimioterapia (EQT) é um novo tratamento paliativo para metástases de pele de melanoma maligno ou de outros tumores, inclusive em pacientes com carcinoma escamoso de cabeça e pescoço. Objetivo: Avaliar o impacto da EQT em pacientes com progressão local de CPT. Método: Quatro pacientes com progressão local de CPT foram tratados com EQT com base em bleomicina, e avaliados em relação ao grau de resposta tumoral, dor local, efeitos colaterais. Resultados: Em todos os casos, foi observado algum grau de resposta tumoral, que perdurou por 6, 7, 12 e 8 meses, respectivamente. Da mesma forma, foi registrada diminuição da dor local e da ansiedade em todos os pacientes. Necrose cutânea na infiltração tumoral foi o único efeito colateral do tratamento. EQT induziu resposta tumoral em todos os pacientes com CPT, com melhora dos sintomas. Conclusões: EQT pode ser uma opção para o tratamento paliativo tópico em pacientes com CPT com progressão tumoral local.
Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Cuidados Paliativos , Bleomicina/administração & dosagem , Neoplasias da Glândula Tireoide/tratamento farmacológico , Carcinoma/tratamento farmacológico , Eletroquimioterapia , Antibióticos Antineoplásicos/administração & dosagem , Carcinoma Papilar , Resultado do Tratamento , Câncer Papilífero da Tireoide , Recidiva Local de NeoplasiaRESUMO
CONCLUSIONS: Weekly paclitaxel may be an active and well tolerated chemotherapy regimen for patients with platin-resistant advanced head and neck cancer. OBJECTIVES: Weekly paclitaxel should be an active and well tolerated regimen for palliative treatment of platin-resistant patients with recurrent or metastatic carcinoma of the head and neck. We analyzed the antitumor activity and toxicity profile. PATIENTS AND METHODS: Sixty consecutive patients with advanced head and neck cancer were treated with 1 h infusion of paclitaxel, 80 mg/m(2) weekly, for 6 consecutive weeks. Patients who showed disease response or disease stabilization continued until progression of disease. RESULTS: A total of 719 doses of paclitaxel were administered to the 60 patients. No complete response was observed. Partial response and stable disease were observed in 26 (43.3%) and 9 (15%) patients, respectively. Median time to tumor progression for patients who responded to therapy was 6.2 months (SD=1.3; 95% CI, 3.7-8.6) and the overall median survival in this group of patients was 8.5 months (SD=1.4; 95% CI, 5.7-11.2). The main toxic effects were leukopenia (26.6%), anemia (43.3%), fatigue (37.4%), alopecia (18.7%), rash/desquamation (13.3%), and thrombophlebitis (6.8%).