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1.
Eur J Cancer ; 208: 114204, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39029295

RESUMO

BACKGROUND: Sotorasib 960 mg once daily is approved to treat KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC). Sotorasib exhibits non-dose proportional pharmacokinetics and clinical responses at lower doses; therefore, we evaluated the efficacy and safety of sotorasib 960 mg and 240 mg. METHODS: In this phase 2, randomized, open-label study, adults with KRAS G12C-mutated advanced NSCLC received sotorasib 960 mg or 240 mg once daily. Primary endpoints were objective response rate (ORR) and safety. Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and pharmacokinetics. The study was not powered for formal statistical hypothesis testing. RESULTS: In the 960 mg group (n = 104), ORR was 32.7 % and DCR was 86.5 %. In the 240 mg group (n = 105), ORR was 24.8 % and DCR was 81.9 %. Median PFS was 5.4 months (960 mg) and 5.6 months (240 mg). At a median follow-up of 17.5 months, median OS was 13.0 months (960 mg) and 11.7 months (240 mg). AUC0-24 h and Cmax were 1.3-fold numerically higher with the 960 mg dose. Treatment-emergent adverse events (TEAEs, ≥10 %) for 960 mg and 240 mg doses, respectively, were diarrhea (39.4 %; 31.7 %), nausea (23.1 %; 19.2 %), increased alanine aminotransaminase (14.4 %; 17.3 %), and increased aspartate aminotransferase (13.5 %; 13.5 %). CONCLUSIONS: Patients treated with sotorasib 960 mg once daily had numerically higher ORR and DCR, and longer DOR and OS, than patients treated with 240 mg in this descriptive analysis. TEAEs were manageable with label-directed dose modifications. CLINICAL TRIAL REGISTRATION: NCT03600883.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Mutação , Proteínas Proto-Oncogênicas p21(ras) , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Masculino , Feminino , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Pessoa de Meia-Idade , Idoso , Proteínas Proto-Oncogênicas p21(ras)/genética , Adulto , Idoso de 80 Anos ou mais , Esquema de Medicação , Piridinas/efeitos adversos , Piridinas/administração & dosagem , Piridinas/farmacocinética , Piridinas/uso terapêutico , Intervalo Livre de Progressão , Piperazinas , Pirimidinas
2.
Eur J Clin Invest ; : e14288, 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39058257

RESUMO

BACKGROUND: Low physical performance is associated with higher mortality rate in multiple pathological conditions. Here, we aimed to determine whether body composition and physical performance could be prognostic factors in non-small cell lung cancer (NSCLC) patients. Moreover, we performed an exploratory approach to determine whether plasma samples from NSCLC patients could directly affect metabolic and structural phenotypes in primary muscle cells. METHODS: This prospective cohort study included 55 metastatic NSCLC patients and seven age-matched control subjects. Assessments included physical performance, body composition, quality of life and overall survival rate. Plasma samples from a sub cohort of 18 patients were collected for exploratory studies in cell culture and metabolomic analysis. RESULTS: We observed a higher survival rate in NSCLC patients with high performance in the timed up-and-go (+320%; p = .007), sit-to-stand (+256%; p = .01) and six-minute walking (+323%; p = .002) tests when compared to NSCLC patients with low physical performance. There was no significant association for similar analysis with body composition measurements (p > .05). Primary human myotubes incubated with plasma from NSCLC patients with low physical performance had impaired oxygen consumption rate (-54.2%; p < .0001) and cell proliferation (-44.9%; p = .007). An unbiased metabolomic analysis revealed a list of specific metabolites differentially expressed in the plasma of NSCLC patients with low physical performance. CONCLUSION: These novel findings indicate that physical performance is a prognostic factor for overall survival in NSCLC patients and provide novel insights into circulating factors that could impair skeletal muscle metabolism.

3.
Nat Commun ; 15(1): 5088, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38898035

RESUMO

Patients with cancer were excluded from pivotal randomized clinical trials of COVID-19 vaccine products, and available observational evidence on vaccine effectiveness (VE) focused mostly on mild, and not severe COVID-19, which is the ultimate goal of vaccination for high-risk groups. Here, using primary care electronic health records from Catalonia, Spain (SIDIAP), we built two large cohorts of vaccinated and matched control cancer patients with a primary vaccination scheme (n = 184,744) and a booster (n = 108,534). Most patients received a mRNA-based product in primary (76.2%) and booster vaccination (99.9%). Patients had 51.8% (95% CI 40.3%-61.1%) and 58.4% (95% CI 29.3%-75.5%) protection against COVID-19 hospitalization and COVID-19 death respectively after full vaccination (two-doses) and 77.9% (95% CI 69.2%-84.2%) and 80.2% (95% CI 63.0%-89.4%) after booster. Compared to primary vaccination, the booster dose provided higher peak protection during follow-up. Calibration of VE estimates with negative outcomes, and sensitivity analyses with slight different population and COVID-19 outcomes definitions provided similar results. Our results confirm the role of primary and booster COVID-19 vaccination in preventing COVID-19 severe events in patients with cancer and highlight the need for the additional dose in this population.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Neoplasias , SARS-CoV-2 , Humanos , COVID-19/prevenção & controle , COVID-19/imunologia , COVID-19/epidemiologia , Espanha/epidemiologia , Neoplasias/imunologia , Masculino , Feminino , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Idoso , Pessoa de Meia-Idade , SARS-CoV-2/imunologia , Adulto , Eficácia de Vacinas , Vacinação , Imunização Secundária , Hospitalização/estatística & dados numéricos , Idoso de 80 Anos ou mais
4.
JCO Glob Oncol ; 10: e2300343, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38603656

RESUMO

Head and neck squamous cell carcinoma (HNSCC) is well known as a serious health problem worldwide, especially in low-income countries or those with limited resources, such as most countries in Latin America. International guidelines cannot always be applied to a population from a large region with specific conditions. This study established a Latin American guideline for care of patients with head and neck cancer and presented evidence of HNSCC management considering availability and oncologic benefit. A panel composed of 41 head and neck cancer experts systematically worked according to a modified Delphi process on (1) document compilation of evidence-based answers to different questions contextualized by resource availability and oncologic benefit regarding Latin America (region of limited resources and/or without access to all necessary health care system infrastructure), (2) revision of the answers and the classification of levels of evidence and degrees of recommendations of all recommendations, (3) validation of the consensus through two rounds of online surveys, and (4) manuscript composition. The consensus consists of 12 sections: Head and neck cancer staging, Histopathologic evaluation of head and neck cancer, Head and neck surgery-oral cavity, Clinical oncology-oral cavity, Head and neck surgery-oropharynx, Clinical oncology-oropharynx, Head and neck surgery-larynx, Head and neck surgery-larynx/hypopharynx, Clinical oncology-larynx/hypopharynx, Clinical oncology-recurrent and metastatic head and neck cancer, Head and neck surgery-reconstruction and rehabilitation, and Radiation therapy. The present consensus established 48 recommendations on HNSCC patient care considering the availability of resources and focusing on oncologic benefit. These recommendations could also be used to formulate strategies in other regions like Latin America countries.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , América Latina/epidemiologia , Consenso , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Neoplasias de Cabeça e Pescoço/terapia
5.
Med. oral patol. oral cir. bucal (Internet) ; 29(2): e280-e287, Mar. 2024. mapas, tab
Artigo em Inglês | IBECS | ID: ibc-231232

RESUMO

Background: There is no consensus about effective systemic therapy for salivary gland carcinomas (sgcs). Our aim was summarized the clinical trials assessing the systemic therapies (ST) on sgcs.Material and Methods: Electronic searches were carried out through MEDLINE/pubmed, EMBASE, Scopus, Web of Science, and the Cochrane Library databases, and gray literature. Results: Seventeen different drugs were evaluated, and the most frequent histological subtype was adenoid cysticcarcinoma (n=195, 45.5%). Stable disease, observed in 11 ST, achieved the highest rate in adenoid cystic carcinoma treated with sunitinib. The highest complete (11.1%) and partial response (30.5%) rates were seen in androgen receptor-positive tumors treated with leuprorelin acetate. Conclusions: Despite all the advances in this field, there is yet no effective evidence-based regimen of ST, with all the clinical trials identified showing low rates of complete and partial responses. Further, translational studies are urgently required to characterize molecular targets and effective ST. (AU)


Assuntos
Humanos , Preparações Farmacêuticas , Carcinoma Adenoide Cístico , Sunitinibe , Androgênios , Neoplasias , Leuprolida , Carcinoma
6.
Head Neck ; 45(9): 2377-2393, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37401537

RESUMO

BACKGROUND: We investigated whether the socioeconomic status (SES) influenced survival rates in oropharynx cancers (OPC), oral cavity cancers (OCC), and larynx cancers (LC) in Brazilian patients. METHODS: This hospital-based cohort study assessed the age-standardized 5-year relative survival (RS) using the Pohar Perme estimator. RESULTS: Overall, we identified 37 191 cases, and 5-year RS were 24.4%, 34.1%, and 44.9% in OPC, OCC, and LC, respectively. In multiple Cox regression, the highest risk of death occurred in the most vulnerable social strata for all subsites-that is, illiterates or patients relying on publicly funded healthcare services. Disparities increased over time by 34.9% in OPC due to the rising of survival rates in the highest SES, whereas they reduced by 10.2% and 29.6% in OCC and LC. CONCLUSIONS: The potential inequities were more significant for OPC than for OCC and LC. It is urgent to tackle social disparities to improve prognoses in highly unequal countries.


Assuntos
Neoplasias de Cabeça e Pescoço , Neoplasias Laríngeas , Neoplasias Bucais , Neoplasias Orofaríngeas , Humanos , Estudos de Coortes , Neoplasias de Cabeça e Pescoço/terapia , Classe Social , Neoplasias Laríngeas/terapia
7.
J Endocr Soc ; 7(7): bvad067, 2023 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-37334212

RESUMO

Background: Parathyroid carcinoma (PC) is a rare and challenging disease without clearly understood prognostic factors. Adequate management can improve outcomes. Characteristics of patients treated for PC over time and factors affecting prognosis were analyzed. Methods: Retrospective cohort study including surgically treated patients for PC between 2000 and 2021. If malignancy was suspected, free-margin resection was performed. Demographic, clinical, laboratory, surgical, pathological, and follow-up characteristics were assessed. Results: Seventeen patients were included. Mean tumor size was 32.5 mm, with 64.7% staged as pT1/pT2. None had lymph node involvement at admission, and 2 had distant metastases. Parathyroidectomy with ipsilateral thyroidectomy was performed in 82.2%. Mean postoperative calcium levels were different between patients who developed recurrence vs those who did not (P = .03). Six patients (40%) had no recurrence during follow-up, 2 (13.3%) only regional, 3 (20%) only distant, and 4 (26.6%) both regional and distant. At 5 and 10 years, 79% and 56% of patients were alive, respectively. Median disease-free survival was 70 months. Neither Tumor, Nodule, Metastasis system nor largest tumor dimension (P = .29 and P = .74, respectively) were predictive of death. En bloc resection was not superior to other surgical modalities (P = .97). Time between initial treatment and development of recurrence negatively impacted overall survival rate at 36 months (P = .01). Conclusion: Patients with PC can survive for decades and have indolent disease course. Free margins seem to be the most important factor in initial surgery. Recurrence was common (60%), but patients with disease recurrence within 36 months of initial surgery had a lower survival rate.

8.
Am J Cancer Res ; 13(12): 6038-6050, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38187064

RESUMO

Despite many progresses in the development of new systemic therapies for oral squamous cell carcinoma (OSCC), the five-year survival rate of OSCC is low. The traditional chemotherapies approach (cisplatin - CDDP) shows some limitations like drug toxicity, limited efficacy, and drug resistance. Promising studies suggested OSCC cancer stem cells (CSC) presented resistance to CDDP. We have previously studied many targets, and we extensively showed the efficacy of the NFκB signaling and the role of histones acetylation, on different malignant tumors, including adenoid cystic carcinoma and mucoepidermoid carcinoma, but until then the effects of the NFkB inhibitor and histone deacetylase (HDAC) inhibitor on the biology of OSCC were not evaluated. Here we assessed the pharmacological inhibitor of NFκB emetine and HDAC inhibitor SAHA on the behavior of CSC derived from OSCC. Our data suggested that CDDP administration resulted in reduced viability of bulk OSCC cells and increased CSC. A single and isolated shot of emetine and SAHA were able to disrupt CSC by inhibiting the NFκB pathway and increasing the histone acetylation levels, respectively. Further, the combined administration of emetine and SAHA presented the same CSC disruption as seen in emetine alone.

9.
Ther Adv Med Oncol ; 14: 17588359221138386, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36506107

RESUMO

Background: A significant proportion of patients with non-small-cell lung cancer (NSCLC) do not respond to immune checkpoint inhibitors (ICIs). Since metabolic reprogramming with increased glycolysis is a hallmark of cancer and is involved in immune evasion, we used 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) to evaluate the baseline glycolytic parameters of patients with advanced NSCLC submitted to ICIs, and assessed their predictive value. Methods: 18F-FDG PET/CT results in the 3 months before ICIs treatment were included. Maximum standardized uptake values, whole metabolic tumor volume (wMTV), and whole-body total lesion glycolysis (wTLG) were evaluated. Cutoff values for high or low glycolytic categories were determined using receiver-operating characteristic curves. Progression-free survival (PFS) and overall survival (OS) were evaluated. Patients with a complete response and a matching group with resistance to ICIs underwent immunohistochemistry analysis. An unsupervised k-means clustering model integrating programmed cell death ligand 1 (PD-L1) expression, glycolytic parameters, and ICIs therapy was performed. Results: In all, 98 patients were included. Lower baseline 18F-FDG PET/CT parameters were associated with responses to ICIs. Patients with low wMTV or wTLG had improved PFS and OS. High wTLG, strong tumor expression of glucose transporter-1, and lack of responses were significantly associated. Patients with low glycolytic parameters benefited from ICIs, regardless of chemotherapy. Conversely, those with high parameters benefited from the addition of chemotherapy. Patients with higher wTLG and lower PD-L1 were associated with progression and worse survival to ICIs monotherapy. Conclusions: Glycolytic metabolic profiles established through baseline 18F-FDG PET/CT are useful biomarkers for evaluating ICI therapy in advanced NSCLC.

11.
J Thorac Oncol ; 17(9): 1122-1129, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35764236

RESUMO

INTRODUCTION: In the phase 1/3 IMpower133 study, atezolizumab plus carboplatin and etoposide (CP/ET) followed by maintenance atezolizumab for first-line treatment of extensive-stage SCLC (ES-SCLC) led to improvement in both overall survival (OS) and progression-free survival (PFS) versus placebo plus CP/ET followed by maintenance placebo. We explored the benefit of atezolizumab versus placebo in the subset of patients who reached the IMpower133 maintenance phase and the safety profile of maintenance therapy. METHODS: Patients with untreated ES-SCLC were randomized 1:1 to four 21-day cycles of CP/ET with atezolizumab or placebo, followed by maintenance atezolizumab or placebo. The primary end points were OS and investigator-assessed PFS. A multivariate Cox model from the start of maintenance treatment was used to evaluate the treatment effect and account for lead-time bias; a generalized linear model was used to identify prognostic or predictive characteristics for reaching the maintenance phase. RESULTS: A similar proportion of patients in each arm received at least the first dose of maintenance therapy (atezolizumab: 77%, n = 154 of 201; placebo: 81%, n = 164 of 202) and were included in the maintenance analysis population. An Eastern Cooperative Oncology Group performance status of 0 and absence of liver metastases at baseline were identified as prognostic factors for reaching the maintenance phase. The positive treatment effect with atezolizumab remained after adjusting for baseline characteristics. Median OS and PFS from the start of maintenance therapy in the atezolizumab versus placebo arm were 12.5 versus 8.4 months (hazard ratio = 0.59, 95% confidence interval: 0.43-0.80) and 2.6 versus 1.8 months (hazard ratio = 0.63 [95% confidence interval: 0.49-0.80]), respectively. Treatment-related adverse events from the start of maintenance therapy occurred in 41% (n = 64 of 155) and 25% (n = 41 of 163) of safety-evaluable patients in the atezolizumab and placebo arms, respectively, and were grade 3 or 4 in 28% (n = 43 of 155) and 23% (n = 37 of 163) of the respective populations; no patient in the atezolizumab arm and one patient in the placebo arm had a grade 5 treatment-related adverse event. CONCLUSIONS: These data in the context of other immunotherapy trials in ES-SCLC suggest that induction with atezolizumab plus CP/ET and maintenance treatment with atezolizumab are important components that contributed to the OS benefit observed in IMpower133. Safety results from randomization and from the start of maintenance therapy were similar between the treatment arms despite the continuation of atezolizumab in the maintenance phase.


Assuntos
Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Carboplatina , Etoposídeo , Humanos
12.
Arch. endocrinol. metab. (Online) ; 66(1): 92-96, Jan.-Feb. 2022. graf
Artigo em Inglês | LILACS | ID: biblio-1364301

RESUMO

SUMMARY We report a rare case of Cushing's syndrome in a 37-year-old female who initially presented with localized acinic cell carcinoma of the parotid gland. In January 2014, she underwent a right parotidectomy with facial nerve preservation and adjuvant radiotherapy. In August 2018, she presented a histologically-proven local regional relapse. The patient was considered for salvage surgery with facial nerve sacrifice and remained with no evidence of disease. One year later the patient developed pulmonary dissemination and started to gain weight and developed facial plethora and acne on the face and upper trunk. In a physical examination, the patient presented moon face, buffalo hump, acne and stage 2 hypertension. Biochemical evaluation confirmed ACTH-dependent Cushing's syndrome. IHC for ACTH in the lung biopsy revealed strong positive staining for ACTH confirming a diagnosis of ectopic ACTH secretion by a metastatic parotid acinic cell carcinoma. Ketoconazole (600 mg/d) was started to treat the CS. In addition, as chemotherapy was initiated to treat the metastatic disease. After the fifth cycle of chemotherapy, ketoconazole was suspended and the patient remained in remission of CS for four months, when CS recurred. A unique feature of this case is related to the clinical CS relapse associated with disease progression, which needed prompt treatment with ketoconazole, resulting in a significant improvement in the patient's condition. Although rare, should be attentive for possible CS features in patients with high-grade salivary gland carcinomas, since the diagnosis of ectopic secretion of ACTH may significantly impact their management and outcomes.


Assuntos
Humanos , Feminino , Adulto , Síndrome de ACTH Ectópico/complicações , Síndrome de ACTH Ectópico/diagnóstico , Neoplasias Parotídeas/complicações , Carcinoma/complicações , Síndrome de Cushing/diagnóstico , Síndrome de Cushing/etiologia , Hormônio Adrenocorticotrópico , Recidiva Local de Neoplasia
13.
J Oral Pathol Med ; 51(6): 553-562, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34661317

RESUMO

AIM: To evaluate the potential use of Cephaeline as a therapeutic strategy to manage mucoepidermoid carcinomas (MEC) of the salivary glands. MATERIAL AND METHODS: UM-HMC-1, UM-HMC-2, and UM-HMC-3A MEC cell lines were used to establish the effects of Cephaeline over tumor viability determined by MTT assay. In vitro wound healing scratch assays were performed to address cellular migration while immunofluorescence staining for histone H3 lysine 9 (H3k9ac) was used to identify the acetylation status of tumor cells upon Cephaeline administration. The presence of cancer stem cells was evaluated by the identification of ALDH enzymatic activity by flow cytometry and through functional assays using in vitro tumorsphere formation. RESULTS: A single administration of Cephaeline resulted in reduced viability of MEC cells along with the halt on tumor growth and cellular migration potential. Administration of Cephaeline resulted in chromatin histone acetylation as judged by the increased levels of H3K9ac and disruption of tumorspheres formation. Interestingly, ALDH levels were increased in UM-HMC-1 and UM-HMC-3A cell lines, while UM-HMC-2 showed a reduced enzymatic activity. CONCLUSION: Cephaeline has shown anti-cancer properties in all MEC cell lines tested by regulating tumor cells' viability, migration, proliferation, and disrupting the ability of cancer cells to generate tumorspheres.


Assuntos
Carcinoma Mucoepidermoide , Acetilação/efeitos dos fármacos , Carcinoma Mucoepidermoide/metabolismo , Linhagem Celular Tumoral , Emetina/análogos & derivados , Emetina/farmacologia , Histonas/metabolismo , Humanos , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/patologia
14.
Curr Oncol Rep ; 23(11): 129, 2021 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-34453267

RESUMO

PURPOSE OF REVIEW: Head and neck cancer is a heterogeneous disease, comprising multiple subsites with diverse etiologic factors, pathology and molecular features, response to treatment, and prognosis. Systemic treatment is usually incorporated in the management of locally advanced head and neck squamous cell carcinoma, and the use of induction chemotherapy has theoretical benefits on reducing the risk of distant metastasis, provide an in vivo testing of response and tumor biology and the potential to allow a more personalized and less toxic local treatment after downstaging. The aim of this review is to access the role of induction chemotherapy in patients with locally advanced oral cavity cancer. RECENT FINDINGS: Clinical trials analyzing this treatment strategy in patients with resectable disease, followed by surgery, and in unresectable disease, followed by (chemo)radiotherapy or surgery are discussed, pointing out strengths and limitations of this data and highlighting the standard treatment in each clinical scenario. Future perspectives, including the incorporation of checkpoint inhibitors and biomarkers for patient selection are discussed. Surgery followed by (chemo)radiation is the standard of care for resectable oral cavity cancer patients, and chemoradiation is the standard for those considered as unresectable. Future trials with the incorporation of immunotherapy and better patient selection based on clinical and molecular biomarkers can bring new hopes for better therapeutic results in these patients.


Assuntos
Quimioterapia de Indução , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/cirurgia , Terapia Combinada , Humanos , Neoplasias Bucais/patologia , Neoplasias Bucais/radioterapia , Cuidados Pré-Operatórios
15.
J Immunother Cancer ; 9(7)2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34315822

RESUMO

A commentary on the original research article: 'Radiomics analysis for predicting pembrolizumab response in patients with advanced rare cancers'. Of note, the predictor selection process, the cross-validation method, along with the lack of final testing of the developed model with a separated data set may mask overfitting, overestimating performance metrics.


Assuntos
Anticorpos Monoclonais Humanizados , Neoplasias , Anticorpos Monoclonais Humanizados/uso terapêutico , Humanos , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico
16.
J Thorac Oncol ; 16(12): 2040-2050, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34311110

RESUMO

INTRODUCTION: The Blood First Assay Screening Trial is an ongoing open-label, multicohort study, prospectively evaluating the relationship between blood-based next-generation sequencing (NGS) detection of actionable genetic alterations and activity of targeted therapies or immunotherapy in treatment-naive advanced or metastatic NSCLC. We present data from the ALK-positive cohort. METHODS: Patients aged more than or equal to 18 years with stage IIIB or IV NSCLC and ALK rearrangements detected by blood-based NGS using hybrid capture technology (FoundationACT) received alectinib 600 mg twice daily. Asymptomatic or treated central nervous system (CNS) metastases were permitted. Primary end point was investigator-assessed objective response rate (ORR; Response Evaluation Criteria in Solid Tumors version 1.1). Secondary end points were independent review facility-assessed ORR, duration of response, progression-free survival (PFS), overall survival, and safety. Exploratory end points were investigator-assessed ORR in patients with baseline CNS metastases and relationship between circulating biomarkers and response. RESULTS: In total, 2219 patients were screened and blood-based NGS yielded results in 98.6% of the cases. Of these, 119 patients (5.4%) had ALK-positive disease; 87 were enrolled and received alectinib. Median follow-up was 12.6 months (range: 2.6-18.7). Confirmed ORR was 87.4% (95% confidence interval [CI]: 78.5-93.5) by investigator and 92.0% (95% CI: 84.1-96.7) by independent review facility. Investigator-confirmed 12-month duration of response was 75.9% (95% CI: 63.6-88.2). In 35 patients (40%) with baseline CNS disease, investigator-assessed ORR was 91.4% (95% CI: 76.9-98.2). Median PFS was not reached; 12-month investigator-assessed PFS was 78.4% (95% CI: 69.1-87.7). Safety data were consistent with the known tolerability profile of alectinib. CONCLUSIONS: These results reveal the clinical application of blood-based NGS as a method to inform clinical decision-making in ALK-positive NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Quinase do Linfoma Anaplásico/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Estudos de Coortes , Crizotinibe , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Inibidores de Proteínas Quinases/uso terapêutico
17.
Cancer Causes Control ; 32(5): 459-471, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33704627

RESUMO

PURPOSE: The rapid spread of the SARS-CoV-2 pandemic around the world caused most healthcare services to turn substantial attention to treatment of these patients and also to alter the structure of healthcare systems to address an infectious disease. As a result, many cancer patients had their treatment deferred during the pandemic, increasing the time-to-treatment initiation, the number of untreated patients (which will alter the dynamics of healthcare delivery in the post-pandemic era) and increasing their risk of death. Hence, we analyzed the impact on global cancer mortality considering the decline in oncology care during the COVID-19 outbreak using head and neck cancer, a known time-dependent disease, as a model. METHODS: An online practical tool capable of predicting the risk of cancer patients dying due to the COVID-19 outbreak and also useful for mitigation strategies after the peak of the pandemic has been developed, based on a mathematical model. The scenarios were estimated by information of 15 oncological services worldwide, given a perspective from the five continents and also some simulations were conducted at world demographic data. RESULTS: The model demonstrates that the more that cancer care was maintained during the outbreak and also the more it is increased during the mitigation period, the shorter will be the recovery, lessening the additional risk of dying due to time-to-treatment initiation. CONCLUSIONS: This impact of COVID-19 pandemic on cancer patients is inevitable, but it is possible to minimize it with an effort measured by the proposed model.


Assuntos
COVID-19 , Carcinoma de Células Escamosas/epidemiologia , Atenção à Saúde , Neoplasias de Cabeça e Pescoço/epidemiologia , SARS-CoV-2 , Tempo para o Tratamento , Carcinoma de Células Escamosas/etiologia , Carcinoma de Células Escamosas/mortalidade , Saúde Global , Neoplasias de Cabeça e Pescoço/etiologia , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Modelos Teóricos , Fatores de Risco
18.
Ecancermedicalscience ; 14: 1100, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33082850

RESUMO

INTRODUCTION: Cancer patients may have a higher risk of severe events and unfavourable outcomes in the setting of COVID-19. This review addresses the question of whether to test asymptomatic cancer patients before initiating systemic cancer treatments. METHODS: This systematic review was conducted based on the PRISMA framework. Pubmed, Embase, Web of Science and Cochrane Central Register of Controlled Trials were systematically searched, as well as guidelines from international institutions involved in cancer care and COVID-19 research. Studies published in English, from 1 December 2019 to 27 May 2020 were considered eligible. We included studies which mentioned testing strategies for SARS-CoV-2 of asymptomatic cancer patients before starting immunosuppressive treatments. RESULTS: We identified 1,163 studies and 4 guidelines through the literature search. A total of 18 articles were considered eligible and were included in the final analysis. Two articles were cohort studies, and the remaining were expert consensuses and published guidelines. The most common recommendation among the studies in this systematic review was to test asymptomatic patients for SARS-CoV-2 prior to treatment. CONCLUSION: There is a lack of studies which directly address COVID-19 testing of asymptomatic patients before treatment. Our systematic review showed that most of the published data favours routine test for SARS-CoV-2 before initiating systemic treatment but failed to identify a good level of evidence to support these recommendations. Based upon this review, we proposed local recommendations at our centre. Each institution should consider the pros and cons of testing asymptomatic patients, evaluating accessibility to testing resources and local epidemiology.

19.
Int Arch Otorhinolaryngol ; 24(3): e258-e266, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32754234

RESUMO

Introduction Coronavirus disease 2019 (COVID-19) is an acute infection caused by the new coronavirus (SARS-CoV-2) and it is highly transmissible, especially through respiratory droplets. To prepare the health system for the care of these patients also led to a restriction in the activity of several medical specialties. Physicians who work with patients affected by diseases of the head and neck region constitute one of the populations most vulnerable to COVID-19 and also most affected by the interruption of their professional activities. Objective The aim of the present study was to assess the impact of the COVID-19 pandemic on the practice of head and neck surgeons and otorhinolaryngologists in Brazil. Methods An anonymous online survey of voluntary participation was applied, containing 30 questions regarding demographic aspects, availability of personal protective equipment (PPE), and impact on the routine of head and neck surgeons and otorhinolaryngologists, as well as clinical oncologists and radiation oncologists who work with head and neck diseases. Results Seven hundred and twenty-nine answers were received in a period of 4 days, ∼ 40 days after the 1 st confirmed case in Brazil. With professionals working in public and private services, there was a high level of concerns with the disease and its consequences, limited availability of PPE and a significant decrease in the volume of specialized medical care. Conclusion The study demonstrated a direct impact of the COVID-19 pandemic on the clinical practice of specialties related to the treatment of patients with diseases of the head and neck region already in the beginning of the illness management in Brazil.

20.
Clinics (Sao Paulo) ; 75: e1615, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32725072

RESUMO

OBJECTIVE: This study aimed to evaluate the effect of the delay to initiate postoperative radiation therapy (RT) on locoregional control to head and neck squamous cell carcinoma patients. METHODS: Retrospective cohort study that included patients submitted to surgery followed by adjuvant RT (with/without chemotherapy). The time interval between surgery and RT was dichotomized by the receiver operating characteristics curve method at 92 days. Other possible sources of heterogeneity with potential impact on locoregional control were explored by regressive analysis. RESULTS: A total of 168 patients were evaluated. The median time for locoregional recurrence (LRR) was 29.7 months. The relapse-free survival rates were 66.4% and 75.4% for patients who initiated RT more than and within 92 postoperative days (p=0.377), respectively. Doses lower than 60Gy were associated with worse rates of locoregional control (HR=6.523; 95%CI:2.266-18.777, p=0.001). Patients whose total treatment time (TTT) was longer than 150 days had LRR rate of 41.8%; no patient with TTT inferior to 150 days had relapses (p=0.001). CONCLUSIONS: The interval between surgery and RT did not show influence on locoregional control rates. However, doses <60Gy and the total treatment time >150 days were associated with lower locoregional control rates.


Assuntos
Neoplasias de Cabeça e Pescoço , Recidiva Local de Neoplasia , Neoplasias de Cabeça e Pescoço/radioterapia , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Período Pós-Operatório , Estudos Retrospectivos , Taxa de Sobrevida
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