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1.
J Thorac Oncol ; 19(2): 285-296, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-37797733

RESUMO

INTRODUCTION: Preclinical evaluation of bintrafusp alfa (BA) combined with radiotherapy revealed greater antitumor effects than BA or radiotherapy alone. In a phase 1 study, BA exhibited encouraging clinical activity in patients with stage IIIB or IV NSCLC who had received previous treatment. METHODS: This multicenter, double-blind, controlled phase 2 study (NCT03840902) evaluated the safety and efficacy of BA with concurrent chemoradiotherapy (cCRT) followed by BA (BA group) versus placebo with cCRT followed by durvalumab (durvalumab group) in patients with unresectable stage III NSCLC. The primary end point was progression-free survival according to Response Evaluation Criteria in Solid Tumors version 1.1 as assessed by the investigator. On the basis of the recommendation of an independent data monitoring committee, the study was discontinued before the maturity of overall survival data (secondary end point). RESULTS: A total of 153 patients were randomized to either BA (n = 75) or durvalumab groups (n = 78). The median progression-free survival was 12.8 months versus 14.6 months (stratified hazard ratio = 1.48 [95% confidence interval: 0.69-3.17]), in the BA and durvalumab groups, respectively. Trends for overall response rate (29.3% versus 32.1%) and disease control rate (66.7% versus 70.5%) were similar between the two groups. Any-grade treatment-emergent adverse events occurred in 94.6% versus 96.1% of patients in the BA versus durvalumab groups, respectively. Bleeding events in the BA group were mostly grade 1 (21.6%) or 2 (9.5%). CONCLUSIONS: BA with cCRT followed by BA exhibited no efficacy benefit over placebo with cCRT followed by durvalumab in patients with stage III unresectable NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Anticorpos Monoclonais/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Quimiorradioterapia , Fatores Imunológicos/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Estadiamento de Neoplasias
2.
J Thorac Oncol ; 18(12): 1731-1742, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37597750

RESUMO

INTRODUCTION: Bintrafusp alfa, a first-in-class bifunctional fusion protein composed of the extracellular domain of TGF-ßRII (a TGF-ß "trap") fused to a human immunoglobulin G1 monoclonal antibody blocking programmed death-ligand 1 (PD-L1), has exhibited clinical activity in a phase 1 expansion cohort of patients with PD-L1-high advanced NSCLC. METHODS: This adaptive phase 3 trial (NCT03631706) compared the efficacy and safety of bintrafusp alfa versus pembrolizumab as first-line treatment in patients with PD-L1-high advanced NSCLC. Primary end points were progression-free survival according to Response Evaluation Criteria in Solid Tumors version 1.1 per independent review committee and overall survival. RESULTS: Patients (N = 304) were randomized one-to-one to receive either bintrafusp alfa or pembrolizumab (n = 152 each). The median follow-up was 14.3 months (95% confidence interval [CI]: 13.1-16.0 mo) for bintrafusp alfa and 14.5 months (95% CI: 13.1-15.9 mo) for pembrolizumab. Progression-free survival by independent review committee was not significantly different between bintrafusp alfa and pembrolizumab arms (median = 7.0 mo [95% CI: 4.2 mo-not reached (NR)] versus 11.1 mo [95% CI: 8.1 mo-NR]; hazard ratio = 1.232 [95% CI: 0.885-1.714]). The median overall survival was 21.1 months (95% CI: 21.1 mo-NR) for bintrafusp alfa and 22.1 months (95% CI: 20.4 mo-NR) for pembrolizumab (hazard ratio = 1.201 [95% CI: 0.796-1.811]). Treatment-related adverse events were higher with bintrafusp alfa versus pembrolizumab; grade 3-4 treatment-related adverse events occurred in 42.4% versus 13.2% of patients, respectively. The study was discontinued at an interim analysis as it was unlikely to meet the primary end point. CONCLUSIONS: First-line treatment with bintrafusp alfa did not exhibit superior efficacy compared with pembrolizumab in patients with PD-L1-high, advanced NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Antígeno B7-H1/metabolismo , Fatores Imunológicos/uso terapêutico
3.
JHEP Rep ; 5(4): 100689, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36937990

RESUMO

Background & Aims: Transcatheter arterial chemoembolisation (TACE) is recommended for patients with hepatocellular carcinoma devoid of macrovascular invasion or extrahepatic spread but not eligible for curative therapies. We compared the efficacy and safety of the combination of a single TACE and external conformal radiotherapy (CRT) vs. classical TACE. Methods: TACERTE was an open-labelled, randomised controlled trial with a 1:1 allocation rate to two or three TACE (arm A) or one TACE + CRT (arm B). Participants had a mean age of 70 years, and 86% were male. The aetiology was alcohol in 85%. The primary endpoint was liver progression-free survival (PFS) in the intention-to-treat population. The typical CRT schedule was 54 Gy in 18 sessions of 3 Gy. Results: Of the 120 participants randomised, 64 were in arm A and 56 in arm B; 100 participants underwent the planned schedule and defined the 'per-protocol' group. In intention-to-treat participants, the liver PFS at 12 and 18 months were 59% and 19% in arm A and 61% and 36% in arm B (hazard ratio [HR] 0.69; 95% CI 0.40-1.18; p = 0.17), respectively. In the per-protocol population, treated liver PFS tended to be better in arm B (HR 0.61; 95% CI 0.34-1.06; p = 0.081) than in arm A. Liver-related grade III-IV adverse events were more frequent in arm B than in arm A. Median overall survival reached 30 months (95% CI 23-35) in arm A and 22 months (95% CI 15.7-26.2) in arm B. Conclusions: Although TACE + CRT tended to improve local control, this first Western randomised controlled trial showed that the combined strategy failed to increase PFS or overall survival and led more frequently to liver-related adverse effects. Impact and implications: Hepatocellular carcinoma is frequently treated by arterial embolisation of the tumour and more recently by external radiotherapy. We tried to determine whether combination of the two treatments (irradiation after embolisation) might produce interesting results. Our results in this prospective randomised study were not able to demonstrate a beneficial effect of combining embolisation and irradiation in these patients. On the contrary, we observed more adverse effects with the combined treatment. Clinical Trials Registration: NCT01300143.

4.
Radiother Oncol ; 183: 109542, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36813175

RESUMO

INTRODUCTION: International guidelines regarding the treatment of squamous cell carcinoma of the anus (SCCA) recommend intensity-modulated radiotherapy (IMRT) combined with mitomycin-based chemotherapy (CT). The French FFCD-ANABASE cohort aimed at evaluating clinical practices, treatment, and outcomes of SCCA patients. METHODS: This prospective multicentric observational cohort included all non-metastatic SCCA patients treated in 60 French centers from January 2015 to April 2020. Patients and treatment characteristics, colostomy-free survival (CFS), disease-free survival (DFS), overall survival (OS), and prognostic factors were analyzed. RESULTS: Among 1015 patients (male: 24.4 %; female: 75.6 %; median age: 65 years), 43.3 %presented with early-stage(T1-2, N0) and 56.7 % with locally advanced stage (T3-4 or N + ) tumors. IMRT was used for 815 patients (80.3 %) and a concurrent CT was administered in 781 patients, consisting of mitomycin-based CT for 80 %. The median follow-up was 35.5 months. DFS, CFS, and OS at 3 years were 84.3 %, 85.6 %, and 91.7 % respectively in the early-stage group compared to 64.4 %, 66.9 %, and 78.2 % in the locally-advanced group (p < 0.001). In multivariate analyses, male gender, locally-advanced stage, and ECOG PS ≥ 1 were associated with poorer DFS, CFS, and OS. IMRT was significantly associated with a better CFS in the whole cohort and almost reached significance in the locally-advanced group. CONCLUSION: Treatment of SCCA patients showed good respect for current guidelines. Significant differences in outcomes advocate for personalized strategies by either de-escalation for early-stage tumors or treatment intensification for locally-advanced tumors.


Assuntos
Neoplasias do Ânus , Carcinoma de Células Escamosas , Radioterapia de Intensidade Modulada , Idoso , Feminino , Humanos , Masculino , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Ânus/tratamento farmacológico , Carcinoma de Células Escamosas/tratamento farmacológico , Quimiorradioterapia/métodos , Estudos de Coortes , Fluoruracila , Mitomicina , Prognóstico , Estudos Prospectivos , Radioterapia de Intensidade Modulada/métodos , Resultado do Tratamento
5.
Strahlenther Onkol ; 199(3): 293-303, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36441171

RESUMO

BACKGROUND AND OBJECTIVE: Transarterial chemoembolization (TACE) is the gold standard treatment in intermediate hepatocellular carcinoma (HCC), but long-term disease control rates remain low. Herein, we compared results of TACE followed by hypofractionated radiotherapy (TACE-hRT) to surgical resection (SR) in early single or paucinodular intrahepatic HCC. METHODS: Between June 2004 and November 2016, data on 160 consecutive patients with Barcelona Clinic Liver Cancer (BCLC) stage A Child-Pugh A HCC treated with SR or TACE-hRT in our expert center were retrospectively reviewed. Time to progression (TTP), progression-free survival (PFS), and overall survival (OS) were evaluated. Clinical outcomes were compared using the stabilized-weights inverse probability of treatment weighting propensity score. RESULTS: Ninety-eight patients underwent SR and 62 were treated by TACE-hRT. Median total dose of RT was 54 Gy (interquartile range [IQR] 54-54) in 3­Gy fractions. Median OS follow-up was 93 months. TTP did not significantly differ between patients following SR and TACE-hRT, with 1­year rates of 68.2% and 82.6% (p = 0.17), respectively. In contrast, PFS and OS were lower in the TACE-hRT group (p = 0.015 and p = 0.006), with a median OS of 37 vs. 63 months for patients with surgery and TACE-hRT, respectively. In multivariate analysis, a significant negative impact on PFS and OS was seen for age at diagnosis, on TTP for alcohol-related liver disease, and on OS for total number of HCC nodules. Symptomatic grade ≥ 3 adverse events were presented by 42 (42.9%) SR and 19 (30.6%) TACE-hRT patients (p = 0.17). CONCLUSION: In patients presenting Child-Pugh A BCLC­A HCC with high risk for surgical complications, TACE-hRT can be an effective and safe treatment. However, surgical management remains the standard of care whenever possible.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Humanos , Estudos Retrospectivos , Quimioembolização Terapêutica/métodos , Estadiamento de Neoplasias , Resultado do Tratamento
6.
J Thorac Oncol ; 18(2): 181-193, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36307040

RESUMO

INTRODUCTION: The phase 3 PACIFIC trial established consolidation therapy with durvalumab as standard of care for patients with unresectable, stage III NSCLC and no disease progression after definitive chemoradiotherapy (CRT). The observational PACIFIC-R study assesses the real-world effectiveness of durvalumab in patients from an early access program. Here, we report treatment characteristics and a preplanned analysis of real-world progression-free survival (rwPFS). METHODS: PACIFIC-R (NCT03798535) is an ongoing, international, retrospective study of patients who started durvalumab (intravenously; 10 mg/kg every 2 wk) within an early access program between September 2017 and December 2018. The primary end points are investigator-assessed rwPFS and overall survival (analyzed by Kaplan-Meier method). RESULTS: As of November 30, 2020, the full analysis set comprised 1399 patients from 11 countries (median follow-up duration, 23.5 mo). Patients received durvalumab for a median of 11.0 months. Median rwPFS was 21.7 months (95% confidence interval: 19.1-24.5). RwPFS was numerically longer among patients who received concurrent versus sequential CRT (median, 23.7 versus 19.3 mo) and among patients with programmed cell death-ligand 1 expression greater than or equal to 1% versus less than 1% (22.4 versus 15.6 mo). Overall, 16.5% of the patients had adverse events leading to treatment discontinuation; 9.5% of all patients discontinued because of pneumonitis or interstitial lung disease. CONCLUSIONS: Consolidation durvalumab after definitive CRT was well tolerated and effective in this large, real-world cohort study of patients with unresectable, stage III NSCLC. As expected, rwPFS was longer among patients who received concurrent versus sequential CRT and patients with higher programmed cell death-ligand 1 expression. Nevertheless, favorable rwPFS outcomes were observed regardless of these factors.


Assuntos
Antineoplásicos Imunológicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Antineoplásicos Imunológicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Quimiorradioterapia , Estudos de Coortes , Ligantes , Neoplasias Pulmonares/tratamento farmacológico , Intervalo Livre de Progressão , Estudos Retrospectivos
7.
Lung Cancer ; 157: 156-162, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34053783

RESUMO

OBJECTIVES: Lymph node dissection (LND) and nodal metastases in thymomas remain controversial and understudied. The aim of our study was to evaluate the incidence of nodal metastasis and the short term outcomes of systematic LND in thymomas. MATERIAL AND METHODS: From December 2017 to September 2020, we performed 54 LND conducted according to the International Thymic Malignancy Interest Group (ITMIG) lymph node map. This group was compared to a historical control group of 55 patients who underwent surgery in our center from January 2015 to November 2017. RESULTS: LND was performed in 72 % and in 5 % of the cases in the study cohort group and historical control group, respectively. The number of lymph nodes retrieved was significantly higher in the study cohort group (3.89 per patient vs. 1.62, p = 0.0021). In the whole population studied, nodal metastases were found in 3 patients (2.8 % of all patients) with 5.6 % in the cohort study group vs. 0 % in the control group (p = 0.12). Patients with nodal metastasis had larger tumors (> 7 cm), and a higher histology grade (B2 and B3). There was a trend towards higher risk of laryngeal nerve palsy in the cohort study group (9.3 % vs. 1.8 %, p = 0.11). CONCLUSION: Systematic LND increases the number of lymph node harvested and detects more lymph node metastases, which remains infrequent in thymomas. The impact of LND and the true prognostic significance of lymph node metastases remains controversial. Given the potential complications, LND or sampling should not be perfomed in small, encapsulated and low grade thymomas.


Assuntos
Neoplasias Pulmonares , Timoma , Neoplasias do Timo , Estudos de Coortes , Humanos , Excisão de Linfonodo , Linfonodos/patologia , Estadiamento de Neoplasias , Estudos Retrospectivos , Timoma/epidemiologia , Timoma/cirurgia , Neoplasias do Timo/epidemiologia , Neoplasias do Timo/patologia , Neoplasias do Timo/cirurgia
8.
Semin Radiat Oncol ; 31(2): 97-104, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33610276

RESUMO

Radiation treatment of early stage nonsmall cell lung cancer has evolved over the past 2 decades to progressively more hypofractionated treatment courses. Results comparable to surgical resection are seen with stereotactic body radiotherapy, which is now the standard of care for medically inoperable patients, and a treatment option for operable patients as well. Understanding of the optimal radiation dose and fractionation are evolving, especially for central tumors which have higher treatment toxicity than peripheral tumors.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Radiocirurgia , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/radioterapia , Estadiamento de Neoplasias , Hipofracionamento da Dose de Radiação , Radiocirurgia/métodos
10.
Clin Colorectal Cancer ; 18(3): 200-208.e1, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31311761

RESUMO

BACKGROUND: Recurrence and distant metastases remain a significant issue in locally advanced rectal cancer (LARC). Several multimodal strategies are assessed in clinical trials. PATIENTS AND METHODS: Patients with mid/low magnetic resonance imaging-defined high-risk LARC were randomized to arm A (12-week bevacizumab + FOLFOX-4 then bevacizumab-5-fluorouracil [5-FU]-radiotherapy [RT] before total mesorectal excision [TME]) or arm B (bevacizumab-5-FU-RT then TME). Long-term efficacy and safety up to 5 years' follow-up are reported. No comparison between arms was planned. RESULTS: Overall, 91 patients (46 in arm A and 45 in arm B) were included. Main results have been presented previously. During the late follow-up period (> 4 weeks after surgery), 4 patients (8.7%) in arm A and 4 (8.9%) in arm B experienced grade 3/4 adverse events related to bevacizumab; the most frequent were 2 anastomotic fistulas (both in arm A) and abscesses (1 in arm A and 2 in arm B). At 5 years' follow-up, 9 (19.6%) and 11 (24.4%) patients in arms A and B developed a fistula in the year after surgery, and 2 (4.3%) in arm A at > 1 year after surgery. Most resolved before study end. Five-year disease-free survival was 70% and 64.3% in arms A and B, respectively. Five-year overall survival was 90.5% (95% confidence interval, 76.7, 96.3) in arm A and 72.7% (95% confidence interval, 56.0, 83.9) in arm B. CONCLUSION: Neoadjuvant bevacizumab + FOLFOX-4 may have the potential to increase survival outcomes when followed by bevacizumab-5-FU-RT and TME in LARC. Bevacizumab-5-FU-RT then TME was associated with a higher-than-projected rate of anastomotic fistulas. Further research of neoadjuvant strategies in LARC is encouraged.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Retais/tratamento farmacológico , Adenocarcinoma/patologia , Adenocarcinoma/radioterapia , Adenocarcinoma/cirurgia , Adolescente , Adulto , Idoso , Bevacizumab/administração & dosagem , Capecitabina/administração & dosagem , Quimiorradioterapia Adjuvante , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Humanos , Leucovorina/administração & dosagem , Metástase Linfática , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Recidiva Local de Neoplasia/patologia , Oxaliplatina/administração & dosagem , Neoplasias Retais/patologia , Neoplasias Retais/radioterapia , Neoplasias Retais/cirurgia , Taxa de Sobrevida , Adulto Jovem
11.
Future Oncol ; 15(21): 2517-2530, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31179766

RESUMO

Aim: To assess neoadjuvant conformal radiotherapy (CRT) before orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC) not suitable for standard locoregional treatments. Methods: Patients undergoing OLT for HCC with or without prior CRT were compared using 1:3 propensity score matching. Results: After propensity score matching, 23 patients with CRT were compared with 66 control subjects. Severe morbidity rate was 34.8 versus 24.2% in the CRT and non-CRT groups (p = 0.289). Complete pathological response was observed in 47.8% of CRT-targeted nodules. The 1-/3-/5-year disease-free survivals were 77.3, 77.3 and 68.7% in the CRT group versus 85.4, 68.0 and 61.7% in the non-CRT group (p = 0.829). Conclusion: Conformal radiotherapy represents a satisfactory neoadjuvant therapy for OLT candidates not suitable for standard HCC locoregional therapies.


Assuntos
Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/terapia , Cuidados Pré-Operatórios , Radioterapia Conformacional , Idoso , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/mortalidade , Terapia Combinada , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/mortalidade , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Morbidade , Terapia Neoadjuvante , Pontuação de Propensão , Radioterapia Conformacional/efeitos adversos , Radioterapia Conformacional/métodos , Estudos Retrospectivos , Resultado do Tratamento
12.
Radiother Oncol ; 135: 74-77, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31015173

RESUMO

BACKGROUND: The role of consolidative thoracic radiotherapy (TRT) in stage IV small cell lung cancer (SCLC) is not uniformly accepted. METHODS: We obtained a list of 13 European medical oncologists from the International Association for the Study of Lung Cancer (IASLC) and 13 European radiation oncologists from the European Society for Therapeutic Radiation Oncology (ESTRO). The strategies in decision making for TRT in stage IV SCLC were collected. Decision trees were created representing these strategies. Frequencies of recommending TRT were analysed for various parameter combinations based on the objective consensus methodology. RESULTS: The factors associated with the recommendation for TRT included fitness of the patient, limited extrathoracic tumour burden, initial bulky thoracic disease and response to chemotherapy. The highest consensus for TRT was in fit patients with limited extrathoracic tumour burden and initial bulky disease with either a complete extrathoracic response or partial thoracic response (92% recommend TRT). For these patients the recommendations were the same for medical and radiation oncologists. In the setting of partial response (intra- and extra-thoracically) without initial bulky thoracic disease radiation oncologists were more likely to recommend TRT than medical oncologists. For unfit patients or for patients with poor overall response to chemotherapy, the majority did not recommend TRT. CONCLUSION: European radiation and medical oncologists specializing in lung cancer recommend TRT in selected patients with stage IV SCLC and restrict its use primarily to fit patients who responded to chemotherapy with limited extrathoracic tumour burden.


Assuntos
Neoplasias Pulmonares/radioterapia , Seleção de Pacientes , Padrões de Prática Médica/estatística & dados numéricos , Radio-Oncologistas/estatística & dados numéricos , Carcinoma de Pequenas Células do Pulmão/radioterapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Estadiamento de Neoplasias , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/patologia , Inquéritos e Questionários , Tórax/patologia , Tórax/efeitos da radiação
13.
Radiother Oncol ; 133: 163-166, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30935574

RESUMO

BACKGROUND: Due to conflicting results between major trials the role of prophylactic cranial irradiation (PCI) in stage IV small cell lung cancer (SCLC) is controversial. METHODS: We obtained a list of 13 European experts from both the European Society for Therapeutic Radiation Oncology (ESTRO) and the International Association for the Study of Lung Cancer (IASLC). The strategies in decision making for PCI in stage IV SCLC were collected. Decision trees were created representing these strategies. Analysis of consensus was performed with the objective consensus methodology. RESULTS: The factors associated with the recommendation for the use of PCI included the fitness of the patient, young age and good response to chemotherapy. PCI was recommended by the majority of experts for non-elderly fit patients who had at least a partial response (PR) to chemotherapy (for complete remission (CR) 85% of radiation oncologists and 69% of medical oncologists, for PR: 85% of radiation oncologists and 54% of medical oncologists). For patients with stable disease after chemotherapy, PCI was recommended by 6 out of 13 (46%) radiation oncologists and only 3 out of 13 medical oncologists (23%). For elderly fit patients with CR, a majority recommended PCI (62%) and no consensus was reached for patients with PR. CONCLUSION: European radiation and medical oncologists specializing in lung cancer recommend PCI in selected patients and restrict its use primarily to fit, non-elderly patients who responded to chemotherapy.


Assuntos
Neoplasias Encefálicas/prevenção & controle , Neoplasias Encefálicas/secundário , Irradiação Craniana/métodos , Neoplasias Pulmonares/radioterapia , Carcinoma de Pequenas Células do Pulmão/radioterapia , Adulto , Idoso , Neoplasias Encefálicas/radioterapia , Tomada de Decisões , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Seleção de Pacientes , Intervalo Livre de Progressão , Radio-Oncologistas , Carcinoma de Pequenas Células do Pulmão/patologia
14.
Joint Bone Spine ; 86(2): 185-194, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-29631067

RESUMO

Bone is the third metastatic site after liver and lungs. Bone metastases occur in one out of three lung cancers and are usually of osteolytic aspect. Osteolytic bone metastases are responsible of long bone and vertebral fractures leading to restricted mobility, surgery and medullar compression that severely alter quality of life and that have a huge medico-economic impact. In the recent years, Bone Metastatic Multidisciplinary Tumour Board (BM2TB) have been developed to optimize bone metastases management for each patient in harmony with oncology program. In this review, we will go through all the different aspects of bone metastases management including diagnosis and evaluation (CT scan, Tc 99m-MDP bone scan, 18FDG-PET scan and biopsy for molecular diagnosis), systemic bone treatments (zoledronic acid and denosumab) and local treatments (interventional radiology and radiotherapy). Surgical strategies will be discussed elsewhere. Based on the last 2017-Lung Cancer South East French Guidelines, we present a practical decision tree to help the physicians for decision making in order to reach a personalized locomotor strategy for every patient.


Assuntos
Neoplasias Ósseas/secundário , Neoplasias Ósseas/terapia , Neoplasias Pulmonares/patologia , Biópsia por Agulha , Neoplasias Ósseas/mortalidade , Terapia Combinada , Gerenciamento Clínico , Feminino , Humanos , Imuno-Histoquímica , Relações Interprofissionais , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/terapia , Imageamento por Ressonância Magnética/métodos , Masculino , Oncologia/métodos , Invasividade Neoplásica , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Prognóstico , Reumatologia/métodos , Medição de Risco , Análise de Sobrevida
15.
Oncotarget ; 9(21): 15757-15765, 2018 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-29644007

RESUMO

BACKGROUND: To evaluate risk of severe breast fibrosis occurrence in patients treated by breast-conserving surgery, adjuvant radiotherapy and hormonotherapy (HT) according to individual radiosensitivity (RILA assay). RESULTS: HT- and RILAhigh were the two independent factors associated with improved breast-fibrosis free survival (BFFS). BFFS rate at 36 months was lower in patients with RILAlow and HT+ than in patients with RILAhigh and HT- (75.8% and 100%, respectively; p = 0.004, hazard ratio 5.84 [95% confidence interval (CI) 1.8-19.1]). Conversely, BFFS at 36 months was comparable in patients with RILAhigh and HT+ and in patients with RILAlow and HT- (89.8% and 93.5%, respectively; p = 0.39, hazard ratio 1.7 [95% CI 0.51-5.65]), showing that these two parameters influenced independently the occurrence of severe breast fibrosis. BFFS rate was not affected by the HT type (tamoxifen or aromatase inhibitor) and timing (concomitant or sequential with radiotherapy). CONCLUSIONS: HT and RILA score independently influenced BFFS rate at 36 months. Patients with RILAhigh and HT- presented an excellent BFFS at 36 months (100%). MATERIALS AND METHODS: Breast Fibrosis-Free Survival (BFFS) rate was assessed relative to RILA categories and to adjuvant HT use (HT+ and HT-, respectively) in a prospective multicentre study (NCT00893035) which enrolled 502 breast cancer patients (456 evaluable patients). Breast fibrosis was recorded according to CTCAE v3.0 grading scale; RILA score was defined according to two categories (<12%: RILAlow; ≥12%: RILAhigh).

16.
Clin Lung Cancer ; 19(6): 476-483, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29544717

RESUMO

INTRODUCTION: Guidelines have recommended prophylactic cranial irradiation (PCI) for patients with limited-stage small-cell lung cancer with at least a partial response after thoracic chemoradiation. However, the survival advantage has been small and was observed in an era before magnetic resonance imaging and surveillance. Neurotoxicity also remains a concern, especially in older adults. Thus, patients have a complex value-laden decision to make. We sought to better understand the role physicians play in patient decision making and introduce a patient decision aid (PDA) to potentially facilitate these discussions. MATERIALS AND METHODS: An e-mail survey was sent to International Association for the Study of Lung Cancer members querying their personal perspectives and professional recommendations regarding PCI for limited-stage small-cell lung cancer. RESULTS: We received 295 responses. Most were from the United States (35%) and Europe (35%) and were radiation (45%) or medical (43%) oncologists. Of those responding, 88% and 50% reported they would recommend PCI to a 50- and 70-year-old patient, respectively. Also, 79% reported that they would wish to receive PCI if faced with this decision. The physicians who would have chosen PCI if faced with the decision were 27.6 and 12.9 times more likely to recommend PCI to a 50- and 70-year-old patient, respectively, than were physicians who would not undergo PCI themselves. Most of the respondents had positive responses to the proposed PDA. CONCLUSION: Physician bias appears to play a role in PCI counseling, and most physicians reported that the provided PDA was better than their present method for discussing PCI and would help patients make such value-laden choices.


Assuntos
Tomada de Decisão Clínica , Irradiação Craniana , Neoplasias Pulmonares/radioterapia , Oncologistas , Papel do Médico , Relações Médico-Paciente , Carcinoma de Pequenas Células do Pulmão/radioterapia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Preferência do Paciente , Inquéritos e Questionários
17.
J Thorac Oncol ; 12(12): 1755-1765, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28962947

RESUMO

Although the effectiveness of screening for lung cancer remains controversial, it is a fact that most lung cancers are diagnosed at an advanced stage outside of lung cancer screening programs. In 2013, the U.S. Preventive Services Task Force revised its lung cancer screening recommendation, now supporting lung cancer screening by low-dose computed tomography in patients at high risk. This is also endorsed by many major medical societies and advocacy group stakeholders, albeit with different eligibility criteria. In Europe, population-based lung cancer screening has so far not been recommended or implemented, as some important issues remain unresolved. Among them is the open question of how enlarging pulmonary nodules detected in lung cancer screening should be managed. This article comprises two parts: a review of the current lung cancer screening approaches and the potential therapeutic options for enlarging pulmonary nodules, followed by a meeting report including consensus statements of an interdisciplinary expert panel that discussed the potential of the different therapeutic options.


Assuntos
Detecção Precoce de Câncer/métodos , Neoplasias Pulmonares/complicações , Programas de Rastreamento/métodos , Nódulos Pulmonares Múltiplos/diagnóstico , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Nódulos Pulmonares Múltiplos/diagnóstico por imagem
18.
J Nucl Med ; 58(7): 1045-1053, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28254869

RESUMO

See an invited perspective on this article on page 1043.This multicenter phase II study investigated a selective radiotherapy dose increase to tumor areas with significant 18F-misonidazole (18F-FMISO) uptake in patients with non-small cell lung carcinoma (NSCLC). Methods: Eligible patients had locally advanced NSCLC and no contraindication to concomitant chemoradiotherapy. The 18F-FMISO uptake on PET/CT was assessed by trained experts. If there was no uptake, 66 Gy were delivered. In 18F-FMISO-positive patients, the contours of the hypoxic area were transferred to the radiation oncologist. It was necessary for the radiotherapy dose to be as high as possible while fulfilling dose-limiting constraints for the spinal cord and lungs. The primary endpoint was tumor response (complete response plus partial response) at 3 mo. The secondary endpoints were toxicity, disease-free survival (DFS), and overall survival at 1 y. The target sample size was set to demonstrate a response rate of 40% or more (bilateral α = 0.05, power 1-ß = 0.95). Results: Seventy-nine patients were preincluded, 54 were included, and 34 were 18F-FMISO-positive, 24 of whom received escalated doses of up to 86 Gy. The response rate at 3 mo was 31 of 54 (57%; 95% confidence interval [CI], 43%-71%) using RECIST 1.1 (17/34 responders in the 18F-FMISO-positive group). DFS and overall survival at 1 y were 0.86 (95% CI, 0.77-0.96) and 0.63 (95% CI, 0.49-0.74), respectively. DFS was longer in the 18F-FMISO-negative patients (P = 0.004). The radiotherapy dose was not associated with DFS when adjusting for the 18F-FMISO status. One toxic death (66 Gy) and 1 case of grade 4 pneumonitis (>66 Gy) were reported. Conclusion: Our approach results in a response rate of 40% or more, with acceptable toxicity. 18F-FMISO uptake in NSCLC patients is strongly associated with poor prognosis features that could not be reversed by radiotherapy doses up to 86 Gy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Fracionamento da Dose de Radiação , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/radioterapia , Misonidazol/análogos & derivados , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Feminino , França , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Misonidazol/farmacocinética , Variações Dependentes do Observador , Compostos Radiofarmacêuticos/farmacocinética , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Taxa de Sobrevida , Resultado do Tratamento , Hipóxia Tumoral/efeitos da radiação
19.
J Thorac Oncol ; 12(2): 194-207, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27729297

RESUMO

Over the past few years, there have been considerable advances in the treatments available to patients with metastatic or locally advanced NSCLC, particularly those who have progressed during first-line treatment. Some of the treatment options available to patients are discussed here, with a focus on checkpoint inhibitor immunotherapies (nivolumab and pembrolizumab) and antiangiogenic agents (bevacizumab, ramucirumab, and nintedanib). It is hypothesized that combining immunotherapy with antiangiogenic treatment may have a synergistic effect and enhance the efficacy of both treatments. In this review, we explore the theory and potential of this novel treatment option for patients with advanced NSCLC. We discuss the growing body of evidence that proangiogenic factors can modulate the immune response (both by reducing T-cell infiltration into the tumor microenvironment and through systemic effects on immune-regulatory cell function), and we examine the preclinical evidence for combining these treatments. Potential challenges are also considered, and we review the preliminary evidence of clinical efficacy and safety with this novel combination in a variety of solid tumor types.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Imunoterapia , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/irrigação sanguínea , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Neoplasias Pulmonares/irrigação sanguínea , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia
20.
Future Oncol ; 12(13): 1577-86, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27095680

RESUMO

AIM: To report a preliminary experience of conformal radiotherapy (CRT) as bridge to orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC). METHODS: Data of 12 patients undergoing CRT for HCC followed by OLT between 2012 and 2014 were reviewed. RESULTS: CRT was used in a neoadjuvant or downstaging setting in nine and three patients, respectively. No radiation-related systemic toxicity was observed. Median blood loss and operating time were 1450 ml (600-4000) and 420 min (240-510), respectively. Four patients had diaphragmatic injury. Complete histological response was observed in six patients, and partial response in five. Seven patients developed severe postoperative morbidity including five anastomosis-related complications and one death. CONCLUSION: CRT for HCC provides satisfactory histological response but may compromise OLT safety.


Assuntos
Carcinoma Hepatocelular/radioterapia , Neoplasias Hepáticas/radioterapia , Transplante de Fígado/métodos , Radioterapia Adjuvante/métodos , Radioterapia Conformacional/métodos , Idoso , Carcinoma Hepatocelular/cirurgia , Quimioembolização Terapêutica , Feminino , Humanos , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estudos Retrospectivos , Resultado do Tratamento
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