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1.
Nat Commun ; 11(1): 4907, 2020 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-32999289

RESUMO

Global alterations in the metabolic network provide substances and energy to support tumor progression. To fuel these metabolic processes, extracellular matrix (ECM) plays a dominant role in supporting the mass transport and providing essential nutrients. Here, we report a fibrinogen and thrombin based coagulation system to construct an artificial ECM (aECM) for selectively cutting-off the tumor metabolic flux. Once a micro-wound is induced, a cascaded gelation of aECM can be triggered to besiege the tumor. Studies on cell behaviors and metabolomics reveal that aECM cuts off the mass transport and leads to a tumor specific starvation to inhibit tumor growth. In orthotopic and spontaneous murine tumor models, this physical barrier also hinders cancer cells from distant metastasis. The in vivo gelation provides an efficient approach to selectively alter the tumor mass transport. This strategy results in a 77% suppression of tumor growth. Most importantly, the gelation of aECM can be induced by clinical operations such as ultrasonic treatment, surgery or radiotherapy, implying this strategy is potential to be translated into a clinical combination regimen.


Assuntos
Materiais Biomiméticos/administração & dosagem , Matriz Extracelular/química , Neoplasias/terapia , Animais , Transporte Biológico/efeitos dos fármacos , Transporte Biológico/efeitos da radiação , Materiais Biomiméticos/química , Materiais Biomiméticos/efeitos da radiação , Linhagem Celular Tumoral/transplante , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Quimiorradioterapia/métodos , Modelos Animais de Doenças , Matriz Extracelular/metabolismo , Matriz Extracelular/efeitos da radiação , Feminino , Fibrinogênio/administração & dosagem , Fibrinogênio/química , Fibrinogênio/efeitos da radiação , Géis , Humanos , Injeções Intravenosas , Metabolômica , Camundongos , Neoplasias/metabolismo , Trombina/administração & dosagem , Trombina/química , Trombina/efeitos da radiação , Terapia por Ultrassom/métodos , Ondas Ultrassônicas
2.
ESMO Open ; 5(5)2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32958531

RESUMO

BACKGROUND: Immunosuppression induced by anticancer therapy in a COVID-19-positive asymptomatic patient with cancer may have a devastating effect and, eventually, be lethal. To identify asymptomatic cases among patients receiving active cancer treatment, the Federico II University Hospital in Naples performs rapid serological tests in addition to hospital standard clinical triage for COVID-19 infection. METHODS: From 6 to 17 April 2020, all candidates for chemotherapy, radiotherapy or target/immunotherapy, if negative at the standard clinical triage on the day scheduled for anticancer treatment, received a rapid serological test on peripheral blood for COVID-19 IgM and IgG detection. In case of COVID-19 IgM and/or IgG positivity, patients underwent a real-time PCR (RT-PCR) SARS-CoV-2 test to confirm infection, and active cancer treatment was delayed. RESULTS: Overall 466 patients, negative for COVID-19 symptoms, underwent serological testing in addition to standard clinical triage. The average age was 61 years (range 25-88 years). Most patients (190, 40.8%) had breast cancer, and chemotherapy with or without immunotherapy was administered in 323 (69.3%) patients. Overall 433 (92.9%) patients were IgG-negative and IgM-negative, and 33 (7.1%) were IgM-positive and/or IgG-positive. Among the latter patients, 18 (3.9%), 11 (2.4%) and 4 (0.9%) were IgM-negative/IgG-positive, IgM-positive/IgG-negative and IgM-positive/IgG-positive, respectively. All 33 patients with a positive serological test, tested negative for RT-PCR SARS-CoV-2 test. No patient in our cohort developed symptoms suggestive of active COVID-19 infection. CONCLUSION: Rapid serological testing at hospital admission failed to detect active asymptomatic COVID-19 infection. Moreover, it entailed additional economic and human resources, delayed therapy administrationand increased hospital accesses.


Assuntos
Infecções Assintomáticas , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/diagnóstico , Imunossupressão/efeitos adversos , Neoplasias/terapia , Pneumonia Viral/diagnóstico , Triagem/normas , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Antineoplásicos Imunológicos/efeitos adversos , Betacoronavirus/genética , Betacoronavirus/imunologia , Betacoronavirus/isolamento & purificação , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Técnicas de Laboratório Clínico/economia , Técnicas de Laboratório Clínico/estatística & dados numéricos , Infecções por Coronavirus/sangue , Infecções por Coronavirus/economia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Testes Diagnósticos de Rotina/economia , Testes Diagnósticos de Rotina/estatística & dados numéricos , Estudos de Viabilidade , Feminino , Humanos , Imunossupressão/métodos , Masculino , Pessoa de Meia-Idade , Neoplasias/imunologia , Pandemias , Admissão do Paciente/economia , Admissão do Paciente/estatística & dados numéricos , Pneumonia Viral/sangue , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Guias de Prática Clínica como Assunto , RNA Viral/isolamento & purificação , Reação em Cadeia da Polimerase Via Transcriptase Reversa/economia , Reação em Cadeia da Polimerase Via Transcriptase Reversa/estatística & dados numéricos , Sensibilidade e Especificidade
3.
Zhonghua Zhong Liu Za Zhi ; 42(8): 676-681, 2020 Aug 23.
Artigo em Chinês | MEDLINE | ID: mdl-32867461

RESUMO

Objective: To evaluate the survival and prognostic factors of radiotherapy in patient with Ⅳ stage esophageal squamous carcinoma treated with radiation or chemoradiation. Methods: The medical records of 608 patients with stage Ⅳ esophageal squamous cell carcinoma who met the inclusion criteria in 10 medical centers in China from 2002 to 2016 were retrospectively analyzed. The overall survival and prognostic factors of all patients at 1, 3 and 5 years were analyzed. Results: The 1-, 3-, 5- year overall survival (OS) rates was 66.7%, 29.5% and 24.3% in stage ⅣA patients, and 58.8%, 29.0% and 23.5% in stage ⅣB patients. There was no statistical difference between the two groups (P=0.255). Univariate analysis demonstrated that the length of lesion, treatment plan, planned tumor target volume (PGTV) dose, subsequent chemotherapy, and degrees of anemia, radiation esophagitis, radiation pneumonia were related to the prognoses of patients with Ⅳ stage esophageal carcinomas after radiotherapy and chemotherapy (P<0.05). Multivariate analysis demonstrated that PGTV dose (OR=0.693, P=0.004), radiation esophagitis (OR=0.867, P=0.038), and radiation pneumonia (OR=1.181, P=0.004) were independent prognostic factors for OS. Conclusions: For patients with stage Ⅳ esophageal squamous cell carcinoma, chemoradiotherapy followed by sequential chemotherapy is recommended, which can extend the total survival and improve the prognosis of the patients. PGTV dose more than 60 Gy has better efficacy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia/métodos , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/radioterapia , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/radioterapia , China/epidemiologia , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/mortalidade , Carcinoma de Células Escamosas do Esôfago/patologia , Humanos , Estadiamento de Neoplasias , Radioterapia de Intensidade Modulada/métodos , Estudos Retrospectivos , Resultado do Tratamento
4.
Medicine (Baltimore) ; 99(33): e21705, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32872045

RESUMO

The optimal treatment strategy of newly diagnosed stage I/II, extranodal nasal-type natural killer/T cell lymphoma (NKTCL) remains unclear. This prospective phase II trial was conducted to explore the short-term and the long-term efficacy and safety of upfront concurrent chemoradiotherapy (CCRT) followed by pegaspargase, gemcitabine, dexamethasone, cisplatin (P-GDP) regimen in patients newly diagnosed with early stage NKTCL.Thirty patients newly diagnosed with stage I/II NKTCL were enrolled from January 2013 to December 2016, and treated as the following strategy: upfront CCRT with cisplatin weekly (25 mg/m) for 5 weeks, followed by 3 cycles of P-GDP regimen chemotherapy (pegaspargase 2500IU/m capped at 3750IU, intramuscular on day 4, gemcitabine 850 mg/m intravenous on days 1 and 8; dexamethasone 40 mg/day intravenous on days 1 to 4; and cisplatin 20 mg/m intravenous on days 1-3) 3 weeks after the completion of CCRT. The objective response rate (ORR) and the complete response (CR) rate were the primary endpoints, and the secondary endpoints were the overall survival (OS), progression-free survival (PFS), and the adverse event (AE).The median follow-up period was 51.5 months (range, 5-78months). The ORR was 93.3% (28/30) and all these 28 patients attained CR at the end of the treatment. Two patients suffered from lymphoma associated hemophagocytic syndrome (LAHS) during the period of consolidation chemotherapy and died within 2 months. The 5-year OS was 93.3%, and the 5-year PFS was 89.4%Mucositis was the most common grades 3/4 nonhematologic AEs (10%, 3/30) of CCRT. During the P-GDP chemotherapy, vomiting (6.7%, 2/30), neutropenia (43.3%, 13/30) and thrombocytopenia (23.3%, 7/30) were the major grades 3/4 toxicities during chemotherapy. No treatment-related deaths occurred.The upfront CCRT followed by P-GDP regimen chemotherapy is an effective and well-tolerated first-line treatment strategy for patients diagnosed with early stage NKTCL. Further investigation of larger sample size is warranted.


Assuntos
Antineoplásicos/uso terapêutico , Quimiorradioterapia/métodos , Quimioterapia de Consolidação/métodos , Linfoma Extranodal de Células T-NK/terapia , Neoplasias Nasais/terapia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Radioterapia de Intensidade Modulada/métodos
5.
Medicine (Baltimore) ; 99(33): e21600, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32872014

RESUMO

INTRODUCTION: Apatinib is a novel anti-angiogenic agent that targets vascular endothelial growth factor receptor-2, and is effective in patients with advanced lung cancer who are refractory to first-line chemotherapy. However, there are limited reports on concurrent apatinib therapy with iodine-125 radioactive seeds brachytherapy in elderly patients with advanced lung cancer. PATIENT CONCERNS: We describe the first reported case of a 70-year-old woman with advanced lung cancer (T3N3M1, stage IV) who received concurrent apatinib and iodine-125 radioactive seeds brachytherapy after the failure of platinum-based doublet chemotherapy DIAGNOSIS:: The patient was diagnosed with left lower lung cancer with mediastinal lymph node metastasis by chest computed tomography. INTERVENTIONS: Initially, apatinib alone was used as second-line cancer therapy. Subsequently, the patient received concurrent apatinib and iodine-125 radioactive seeds brachytherapy. OUTCOMES: The patient achieved partial response shortly after undergoing treatment with only apatinib. During the treatment, the tumor continued to respond to apatinib therapy, and the lung metastases were diminished eventually. However, a chest computed tomography scan showed a large cavity in the lung tumor. Thereafter, the patient received concurrent apatinib and iodine-125 radioactive seeds brachytherapy. Unfortunately, she died due to pulmonary infection. CONCLUSION: Apatinib alone may be a good second-line therapy for advanced lung cancer patients who are refractory to platinum-based doublet chemotherapy. However, its potential benefits, especially as combination therapy, need further investigation by future prospective clinical studies. Elderly patients with advanced lung cancer may benefit from concurrent apatinib with iodine-125 radioactive seeds brachytherapy when chemotherapy is not tolerated or effective. Further studies are needed to investigate the clinical outcomes and toxicities associated with concurrent apatinib and radiation therapy in patients with advanced lung cancer.


Assuntos
Braquiterapia/métodos , Carcinoma Pulmonar de Células não Pequenas/terapia , Quimiorradioterapia/métodos , Neoplasias Pulmonares/terapia , Piridinas/uso terapêutico , Idoso , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Radioisótopos do Iodo/administração & dosagem , Neoplasias Pulmonares/patologia , Metástase Linfática , Estadiamento de Neoplasias , Piridinas/administração & dosagem
6.
Medicine (Baltimore) ; 99(39): e22283, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32991429

RESUMO

For patients with locoregionally advanced nasopharyngeal carcinoma (NPC), induction chemotherapy (IC) regimens based on TPF (docetaxel, cisplatin, and 5-fluorouracil), TP (docetaxel and cisplatin), and GP (gemcitabine and cisplatin) have shown excellent survival outcomes as the first-line therapy; however, no trials comparing the efficacy and safety of TPF, TP, and GP have been reported. We report 2 phase II trials comparing the treatment outcomes and side effects of 3 different IC regimens followed by concurrent chemoradiotherapy in locoregionally advanced patients with NPC.A total of 206 locoregionally advanced patients with NPC treated with a combination treatment from January 2012 to January 2014 were enrolled in the 2 studies. The patients received TPF-, TP-, and GP-based IC regimens every 3 weeks, followed by intensity-modulated radiotherapy and concurrent therapy with cisplatin every 3 weeks.After a median follow-up duration of 47 months (10-60 months), the 3-year local recurrence-free survival, regional recurrence-free survival, distant metastases-free survival, progression-free survival, and overall survival rates were 96.4%, 100%, 87.7%, 86%, and 94.7% in the TPF arm; 91.7%, 95.9%, 91.9%, 85.2%, and 92% in the TP arm; 98.6%, 100%, 89.0%, 87.6%, and 89.2% in the GP arm. The survival differences among the 3 arms were not statistically significant (P > .05). The multivariate analysis demonstrated that the IC regimen was not an independent prognostic factor for any survival outcomes. The patients in the TP arm experienced significantly lower grade 3/4 toxicities than the patients in the other 2 arms.TP-based IC regimen has similar efficacy compared with TPF- and GP-based IC regimens; however, TP-based IC regimen has a lower toxicity profile.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia/métodos , Neoplasias Nasofaríngeas/terapia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Intervalo Livre de Doença , Humanos , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/patologia , Estudos Prospectivos , Radioterapia de Intensidade Modulada , Adulto Jovem
7.
Clinics (Sao Paulo) ; 75: e1553, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32935821

RESUMO

OBJECTIVES: To assess the patterns of failure and prognostic factors in Brazilian patients with glioblastoma multiforme (GBM) treated with radiotherapy (RT) and concurrent and adjuvant temozolomide (TMZ). METHODS: Patients with diagnosed GBM post-resection received postoperative RT. TMZ was administered concurrently at 75 mg/m2/day for 28 consecutive days and adjuvant therapy at 150-200 mg/m2/day for 5 days every 28 days. Radiographic failure was defined as any new T1-enhancing lesion or biopsy-confirmed progressive enhancement inside of the radiation field. When possible, patients with recurrence were salvaged with metronomic TMZ, either in combination with a local treatment or alone (surgery or re-irradiation). Several prognostic factors were evaluated for overall survival (OS). Univariate and multivariate analyses were performed to identify significant factors. A p-value <0.05 was considered significant. RESULTS: This study included 50 patients. The median follow-up time was 21 months. The median RT dose was 60 Gy and all patients received concomitant TMZ. During follow-up, 41 (83.6%) failures were observed, including 34 (83%) in-field, 4 (9.7%) marginal, and 3 (7.3%) distant failures. Metronomic TMZ was used as salvage treatment in 22 (44%) cases and in combination with local treatment in 12 (24%) cases. The median OS and progression-free survival times for the entire cohort were 17 and 9 months, respectively. In univariate analysis, the following factors were significant for better OS: maximal surgical resection (p=0.03), Karnofsky Performance Score (KPS)>70 at diagnosis (p=0.01), metronomic TMZ treatment (p=0.038), recursive partitioning analysis class III (p=0.03), and time to failure >9 months (p=0.0001). In multivariate analysis, the following factors remained significant for better OS: metronomic TMZ (p=0.01) and time to failure >9 months (p=0.0001). CONCLUSION: The median OS of Brazilian patients with GBM treated with RT and TMZ was satisfactory. Although TMZ therapy has become the standard of care for patients with newly diagnosed GBM, the recurrence rate is extremely high. Metronomic TMZ as salvage treatment improved survival in these patients.


Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Encefálicas/terapia , Quimiorradioterapia/métodos , Glioblastoma/terapia , Recidiva Local de Neoplasia/epidemiologia , Temozolomida/uso terapêutico , Neoplasias Encefálicas/patologia , Brasil/epidemiologia , Quimioterapia Adjuvante , Feminino , Glioblastoma/mortalidade , Glioblastoma/patologia , Humanos , Masculino , Estudos Retrospectivos , Sobrevida , Resultado do Tratamento
8.
Medicine (Baltimore) ; 99(35): e21304, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32871861

RESUMO

To determine the efficacy of neoadjuvant chemoradiotherapy (NCRT) between young and old patients with locally advanced rectal cancer (LARC) in terms of tumor response and survival outcome.LARC patients undergoing NCRT and radical surgery from 2011 to 2015 were included and divided into: young (aged ≤50 years) and old group (aged >50 years). Multivariate analyses were performed to identify risk factors for local recurrence. Least absolute shrinkage and selection operator analysis was performed to identify risk factors for overall survival. Predicting nomograms and time-indepent receiver operating characteristic curve analysis were performed to compare the models containing with/withour age groups.A total of 572 LARC patients were analyzed. The young group was associated with higher pathological TNM stage, poorly differentiated tumors, and higher rate of positive distal resection margin (P = .010; P = .019; P = .023 respectively). Young patients were associated with poorer 5-year disease-free survival and local recurrence rates (P = .023, P = .003 respectively). Cox regression analysis demonstrated that age ≤50 years (Hazard ratio = 2.994, P = .038) and higher pathological TNM stage (Hazard ratio = 3.261, P = .005) were significantly associated with increased risk for local recurrence. Least absolute shrinkage and selection operator analysis and the time-indepent receiver operating characteristic curve analysis demonstrated that including the age group were superior than that without age group.Young patients were associated with poorer disease free survival (DFS) and a higher risk for local recurrence in LARC following NCRT. The predicting model basing based on the age group had a better predictive ability. More intense adjuvant treatment could be considered to improve DFS and local control for young patients with LARC following NCRT.


Assuntos
Terapia Neoadjuvante/métodos , Recidiva Local de Neoplasia/mortalidade , Neoplasias Retais/patologia , Neoplasias Retais/terapia , Adulto , Idoso , Quimiorradioterapia/métodos , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Estadiamento de Neoplasias/métodos , Nomogramas , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
9.
Medicine (Baltimore) ; 99(36): e21785, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32899005

RESUMO

BACKGROUND: Concurrent cisplatin with radiotherapy (CRT) or concurrent cetuximab with radiotherapy (BRT) improves outcomes in locally advanced head and neck squamous cell carcinoma (HNSCC) compared with radiotherapy alone. Nevertheless, a detailed comparison between CRT and BRT in locally advanced HNSCC is required due to inconclusive results. METHODS: A comprehensive literature search was conducted on PubMed, Web of Science, Cochrane databases, and EMBASE. Studies that evaluated CRT vs BRT in locally advanced HNSCC were included. The primary outcome that was overall survival (OS), whereas the secondary outcomes were progression-free survival (PFS), locoregional control (LRC), and distant metastasis-free survival (DMFS). Pooled hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) were used to evaluate prognosis. All the analyses were performed using Stata Statistical Software 12.0. RESULTS: Twenty-three studies, with a total of 8701 patients, were considered eligible and included in this meta-analysis. Our results revealed that patients treated with CRT had longer OS (HR = 0.51, 95%CI, 0.41-0.64, P < .001), PFS (HR = 0.37, 95%CI, 0.23-0.60, P < .001), LRC (HR = 0.46, 95%CI, 0.37-0.57, P < .001), and DMFS (HR = 0.56, 95%CI, 0.40-0.77, P < .001) than those treated with BRT. Furthermore, the results of the subgroup analyses were consistent with the primary analysis. CONCLUSIONS: CRT has a better OS, PFS, LRC, and DMFS than BRT in locally advanced HNSCC, and should be the preferred treatment for patients with the disease.


Assuntos
Cetuximab/uso terapêutico , Cisplatino/uso terapêutico , Neoplasias de Cabeça e Pescoço/terapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Idoso , Quimiorradioterapia/métodos , Intervalo Livre de Doença , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade
10.
Medicine (Baltimore) ; 99(30): e21325, 2020 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-32791728

RESUMO

The present study aimed to retrospectively analyze the survival outcomes and prognostic factors for patients with nasopharyngeal carcinoma (NPC) receiving intensity-modulated radiotherapy (IMRT).Clinical data was collected from 691 patients with NPC receiving IMRT from January 2009 to August 2015. A survival analysis was performed and prognostic factors were analyzed using the Kaplan-Meier method, the Cox proportional hazards regression model, and the log-rank test.The median follow-up time was 62.8 months. Sixty-three patients experienced relapse, 44 cases (70%) of which occurred within 3 years. Six cases (9.5%) remained in remission for over 5 years. Seventy-two patients developed metastasis, 63 cases (87.5%) of which occurred within 3 years and only 1 case occurred after 5 years (1.3%). Five-year disease special survival (DSS), progression free survival, locoregional recurrence free survival, and distant metastasis free survival were 86.5%, 82.5%, 90.7%, and 89.4%, respectively in patients with NPC. Patients with stage III NPC with and without induction chemotherapy had 5-year DSS rates of 95.8% and 89.3%, respectively (P = .00). Patients with stage IVa NPC with and without induction chemotherapy had 5-year DSS rates of 73.1% and 68.9%, respectively (P = .04). The 5-year DSS rates of patients with stage III with or without concurrent chemotherapy were 92.8% and 85.5%, respectively (P = .04). The 5-year DSS rates of patients with stage IV with or without concurrent chemotherapy were 72.7% and 53.0% (P = .02).IMRT improves the survival rate of patients with NPC. Recurrence and metastasis mainly occur within 2 to 3 years after radiotherapy. Induction and concurrent chemotherapy improve the 5-year DSS of patients with locally advanced NPC.


Assuntos
Quimiorradioterapia/efeitos adversos , Quimioterapia de Indução/efeitos adversos , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/patologia , Radioterapia de Intensidade Modulada/métodos , Quimiorradioterapia/métodos , Feminino , Seguimentos , Humanos , Quimioterapia de Indução/métodos , Masculino , Carcinoma Nasofaríngeo/mortalidade , Metástase Neoplásica/patologia , Estadiamento de Neoplasias/métodos , Intervalo Livre de Progressão , Recidiva , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
11.
PLoS One ; 15(8): e0237114, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32760099

RESUMO

BACKGROUND: This study aimed to investigate the correlation between primary tumor volume and cancer failure patterns in esophageal squamous cell carcinoma (ESCC) treated with definitive concurrent chemoradiotherapy (CCRT) and examine whether increasing radiation dose can improve the outcome. METHODS: We retrospectively reviewed 124 patients with stage III ESCC treated by definitive CCRT. The primary tumor volume calculated from the radiotherapy planning computed tomography scans was correlated to treatment response, time to disease progression, and overall survival. We further analyzed whether a higher radiation dose correlated with better disease control and patient survival. RESULTS: Patients with poor CCRT response had a larger primary tumor volume than those with good response (97.9 vs 64.3 cm3, P = 0.032). The optimal cutoff value to predict CCRT response was 55.3 cm3. Large primary tumor volume (≥ 55.3 cm3) correlated with shorter time to tumor progression in the esophagus (13.6 vs 48.6 months, P = 0.033) compared with small tumor volume (< 55.3 cm3). For the large esophageal tumors (≥ 55.3 cm3), radiation dose > 60 gray significantly prolonged the time to tumor progression in esophagus (20.3 vs 10.1 months, P = 0.036) and overall survival (12.2 vs 8.0 months, P = 0.030), compared with dose ≤ 60 gray. In contrast, higher radiation dose did not benefit local disease control or overall survival in the small esophageal tumors (< 55.3 cm3). CONCLUSION: Large primary tumor volume correlates with poor local control and overall survival in ESCC treated with definitive CCRT. Radiation dose > 60 gray can improve the outcomes in patients with large primary tumor. Further prospective dose escalation trials are warranted.


Assuntos
Carcinoma de Células Escamosas/terapia , Quimiorradioterapia/métodos , Neoplasias Esofágicas/terapia , Doses de Radiação , Idoso , Carcinoma de Células Escamosas/patologia , Neoplasias Esofágicas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dosagem Radioterapêutica , Carga Tumoral
12.
Cancer Radiother ; 24(6-7): 594-601, 2020 Oct.
Artigo em Francês | MEDLINE | ID: mdl-32773282

RESUMO

Therapeutic strategies combining irradiation and drugs including chemotherapy, hormonotherapy, but also more recently targeted therapy and immunotherapy are routinely used for cancer treatment. Nevertheless, combined treatments usually lead to a rise in toxicity. In order to increase the therapeutic ratio in favour of a multimodality treatment, adapting dose constraints to organs at risk may be the key to lower the risk of toxicity. A review of the literature was conducted, focusing on the toxicity in dose-limiting organs at risk when radiation therapy is associated with drugs. Four situations were differentiated, including : 1) some contraindicated combinations due to an inacceptable increased of toxicity, or recommendations of careful use with restricted indications, reduction in prescribed dose, or severe dose constraints to organs at risk, 2) combined treatments without increased toxicity with no arguments for adjusted dose constraints, 3) associations with higher risk of toxicity, for which dose constraints could be adapted, 4) combined therapies with limited tolerance data, prohibiting their use out of clinical trials.


Assuntos
Quimiorradioterapia , Neoplasias/terapia , Órgãos em Risco/efeitos da radiação , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Humanos , Neoplasias/tratamento farmacológico , Dosagem Radioterapêutica
13.
Cancer Radiother ; 24(6-7): 586-593, 2020 Oct.
Artigo em Francês | MEDLINE | ID: mdl-32861607

RESUMO

Concurrent chemoradiotherapy improves the outcome of locally advanced head and neck cancers and the current reference chemotherapy is cisplatin. These results are obtained at the cost of increased toxicities. To limit the risk of toxicity, organ at riskdose constraints have been established starting with 2D radiotherapy, then 3D radiotherapy and intensity-modulated radiotherapy. Regarding grade ≥3 acute toxicities, the scientific literature attests that concurrent chemoradiotherapy significantly increases risks of mucositis and dysphagia. Constraints applied to the oral mucosa volume excluding the planning target volume, the pharyngeal constrictor muscles and the larynx limit this adverse impact. Regarding late toxicity, concurrent chemoradiotherapy increases significantly the risk of postoperative neck fibrosis and hearing loss. However, for some organs at risk, concurrent chemotherapy appears to increase late radiation induced effect, even though the results are less marked (brachial plexus, mandible, pharyngeal constrictor muscles, parotid gland). This additional adverse impact of concomitant chemotherapy may be notable only when organs at risk receive less than their usual dose thresholds and this would be vanished when those thresholds are exceeded as seems to be the situation for the parotid glands. Until the availability of more robust data, it seems appropriate to apply the principle of delivering dose to organs at risk as low as reasonably achievable.


Assuntos
Quimiorradioterapia , Neoplasias de Cabeça e Pescoço/terapia , Órgãos em Risco/efeitos da radiação , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Humanos , Dosagem Radioterapêutica
14.
Lancet Oncol ; 21(8): 1110-1122, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32702309

RESUMO

BACKGROUND: Outcomes for children and adults with advanced soft tissue sarcoma are poor with traditional therapy. We investigated whether the addition of pazopanib to preoperative chemoradiotherapy would improve pathological near complete response rate compared with chemoradiotherapy alone. METHODS: In this joint Children's Oncology Group and NRG Oncology multicentre, randomised, open-label, phase 2 trial, we enrolled eligible adults (aged ≥18 years) and children (aged between 2 and <18 years) from 57 hospitals in the USA and Canada with unresected, newly diagnosed trunk or extremity chemotherapy-sensitive soft tissue sarcoma, which were larger than 5 cm in diameter and of intermediate or high grade. Eligible patients had Lansky (if aged ≤16 years) or Karnofsky (if aged >16 years) performance status score of at least 70. Patients received ifosfamide (2·5 g/m2 per dose intravenously on days 1-3 with mesna) and doxorubicin (37·5 mg/m2 per dose intravenously on days 1-2) with 45 Gy preoperative radiotherapy, followed by surgical resection at week 13. Patients were randomly assigned (1:1) using a web-based system, in an unmasked manner, to receive oral pazopanib (if patients <18 years 350 mg/m2 once daily; if patients ≥18 years 600 mg once daily) or not (control group), with pazopanib not given immediately before or after surgery at week 13. The study projected 100 randomly assigned patients were needed to show an improvement in the number of participants with a 90% or higher pathological response at week 13 from 40% to 60%. Analysis was done per protocol. This study has completed accrual and is registered with ClinicalTrials.gov, NCT02180867. FINDINGS: Between July 7, 2014, and Oct 1, 2018, 81 eligible patients were enrolled and randomly assigned to the pazopanib group (n=42) or the control group (n=39). At the planned second interim analysis with 42 evaluable patients and a median follow-up of 0·8 years (IQR 0·3-1·6) in the pazopanib group and 1 year (0·3-1·6) in the control group, the number of patients with a 90% pathological response or higher was 14 (58%) of 24 patients in the pazopanib group and four (22%) of 18 patients in the control group, with a between-group difference in the number of 90% or higher pathological response of 36·1% (83·8% CI 16·5-55·8). On the basis of an interim analysis significance level of 0·081 (overall one-sided significance level of 0·20, power of 0·80, and O'Brien-Fleming-type cumulative error spending function), the 83·8% CI for response difference was between 16·5% and 55·8% and thus excluded 0. The improvement in pathological response rate with the addition of pazopanib crossed the predetermined boundary and enrolment was stopped. The most common grade 3-4 adverse events were leukopenia (16 [43%] of 37 patients), neutropenia (15 [41%]), and febrile neutropenia (15 [41%]) in the pazopanib group, and neutropenia (three [9%] of 35 patients) and febrile neutropenia (three [9%]) in the control group. 22 (59%) of 37 patients in the pazopanib group had a pazopanib-related serious adverse event. Paediatric and adult patients had a similar number of grade 3 and 4 toxicity. There were seven deaths (three in the pazopanib group and four in the control group), none of which were treatment related. INTERPRETATION: In this presumed first prospective trial of soft tissue sarcoma spanning nearly the entire age spectrum, adding pazopanib to neoadjuvant chemoradiotherapy improved the rate of pathological near complete response, suggesting that this is a highly active and feasible combination in children and adults with advanced soft tissue sarcoma. The comparison of survival outcomes requires longer follow-up. FUNDING: National Institutes of Health, St Baldrick's Foundation, Seattle Children's Foundation.


Assuntos
Antineoplásicos/administração & dosagem , Quimiorradioterapia/métodos , Terapia Neoadjuvante/métodos , Pirimidinas/administração & dosagem , Sarcoma/tratamento farmacológico , Neoplasias de Tecidos Moles/tratamento farmacológico , Sulfonamidas/administração & dosagem , Adolescente , Adulto , Antineoplásicos/efeitos adversos , Quimiorradioterapia/efeitos adversos , Quimioterapia Adjuvante/efeitos adversos , Quimioterapia Adjuvante/métodos , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Pirimidinas/efeitos adversos , Radioterapia Adjuvante , Sarcoma/radioterapia , Neoplasias de Tecidos Moles/radioterapia , Sulfonamidas/efeitos adversos , Adulto Jovem
15.
Anticancer Res ; 40(8): 4237-4244, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32727750

RESUMO

BACKGROUND/AIM: To study the changes of glioblastoma multiforme during chemoradiotherapy (CRT) and to evaluate the impact of changes on dosimetry and clinical outcomes. PATIENTS AND METHODS: Forty-three patients underwent volumetric imaging-based replanning. Prognostic factors and gross tumor volume changes in relation to overall survival and the effect of adaptive replanning were statistically analyzed. RESULTS: Patients with total tumor removal, with shorter time to CRT (<27 days), with methylated O-6 methylguanine DNA methyltransferase and good performance status (>60%) had better survival. Tumor shrinkage in 24 patients resulted in improved survival compared to 19 in whom tumor was unchanged or progressed (25.3 vs. 11.1 months, p=0.04). Adapted planning target volume allowed a reduction in irradiated volume, while increasing survival (12.06 vs. 28.98 months, p=0.026). CONCLUSION: Tumor response during CRT has significant impact on the outcome. Adaptation of the planning target volume to the tumor changes proved to be beneficial and warrants further investigation.


Assuntos
Neoplasias Encefálicas/radioterapia , Glioblastoma/radioterapia , Planejamento da Radioterapia Assistida por Computador/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/tratamento farmacológico , Quimiorradioterapia/métodos , Criança , Pré-Escolar , Feminino , Glioblastoma/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
16.
Medicine (Baltimore) ; 99(29): e20443, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32702809

RESUMO

BACKGROUND: Although common, the use of concurrent chemoradiotherapy with adjuvant chemotherapy for stage II nasopharyngeal carcinoma (NPC) is controversial due to its undefined clinical benefits. We, therefore, conducted a retrospective cohort study to investigate whether adjuvant chemotherapy confers survival gains to stage II NPC patients. METHODS: In this study, we examined whether combining adjuvant chemotherapy (AC) and/or concurrent chemotherapy with radiotherapy (CCRT) improved survival in patients with stage II NPC. Three hundred thirty-five stage II NPC patients were retrospectively analyzed between June 2003 and June 2016 and received CCRT; some patient groups also received AC every 3 weeks for 2 to 3 cycles. RESULTS: The median follow-up duration was 72 months for all patients (range, 26-151 months) and the estimated 5-year locoregional relapse-free survival (LRRFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) rates were 95.1%, 97.8%, 93.5%, and 94.3%. At the last follow-up, there were no statistically significant differences among the CCRT and CCRT+AC groups in 5-year LRRFS (95.2% vs 94.9%, P = .599), DMFS (98.5% vs 92.4%, P = .152), PFS (93.8% vs 90.2%, P = .599), or OS (95.5% vs 93.9%, P = .682) rates. CONCLUSION: The analyses revealed that a combined regimen was not an independent prognostic factor for any survival outcome. However, patients who received CCRT plus AC experienced more acute adverse events than those who received CCRT alone. Thus, the addition of AC to CCRT did not improve survival outcomes, but was associated with higher incidences of acute treatment-associated toxicities than CCRT alone in patients with stage II NPC.


Assuntos
Quimiorradioterapia/métodos , Quimioterapia Adjuvante/métodos , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/patologia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica , Quimiorradioterapia/efeitos adversos , Quimioterapia Adjuvante/efeitos adversos , Terapia Combinada/métodos , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/mortalidade , Estadiamento de Neoplasias , Prognóstico , Radioterapia de Intensidade Modulada/efeitos adversos , Radioterapia de Intensidade Modulada/métodos , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
17.
Am Surg ; 86(6): 703-714, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32683973

RESUMO

There is a controversy regarding the optimal time to assess anal squamous cell carcinoma (SCC) response to chemoradiation and when salvage abdominoperineal resection (APR) should be offered. A retrospective cohort study was performed on patients with stage I-III anal SCC treated with chemoradiation in the National Cancer Database (2004-2015). The time between radiation and APR was recorded. Logistic regression and Cox proportional hazard analysis were used to determine predictors of resection margin status and overall survival. The cohort included 23 050 patients, of whom 545 (2.4%) underwent salvage APR. The median (IQR) time between radiation and resection was 3.8 (2.4-5.5) months. The rate of positive margins was 19.0%. Positive margins were more common in male, non-white patients with larger tumors, pathologic upstaging of T stage, and ≥3 months between chemoradiation and resection (all P < .05). Observing for ≥3 months between chemoradiation and APR remained associated with positive margins, even after adjusting for pretreatment tumor size (odds ratio = 2.56, 95% CI 1.46-4.47). Our data, based on the largest published cohort of anal SCC patients treated with chemoradiation and subsequent APR, suggest that patients at high risk of local treatment failure, particularly non-white men with large tumors, may benefit from early interim restaging and earlier consideration of salvage surgery.


Assuntos
Neoplasias do Ânus , Carcinoma de Células Escamosas , Quimiorradioterapia/métodos , Terapia de Salvação/métodos , Adulto , Idoso , Neoplasias do Ânus/patologia , Neoplasias do Ânus/terapia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Terapia Combinada , Feminino , Humanos , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo
18.
Anticancer Res ; 40(7): 4095-4104, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32620658

RESUMO

BACKGROUND/AIM: To evaluate treatment schedules involving concurrent chemoradiotherapy in stage III non-small cell lung cancer (NSCLC) using the tumor control probability (TCP) and normal tissue complication probability (NTCP) parameters. PATIENTS AND METHODS: The standard schedules were compared with two types of schedules, the dose escalation and the short-term schedules. Standard schedules were 60-74 Gy in 30-37 fractions. The dose escalation schedules with hypofractionation and hyperfractionation were 69 Gy in 30 fractions and 69.6 Gy in 58 fractions, respectively, twice per day (b.i.d). The short-term schedules were concomitant boost, 64 Gy in 40 fractions b.i.d. and the accelerated radiotherapy schedule, 57.6 Gy in 36 fractions, three fractions per day (t.i.d). RESULTS: The average TCP for the short-term schedules was more than 16% in two tumor models; however, the TCP for standard and dose escalation schedules was less than 5%. In each organ, the increase in NTCP for the short-term schedule compared with standard schedules was less than 15%. CONCLUSION: The short-term schedules had an advantage over standard schedules for NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/terapia , Quimiorradioterapia/métodos , Fracionamento da Dose de Radiação , Neoplasias Pulmonares/terapia , Algoritmos , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Neoplasias Pulmonares/patologia , Estadiamento de Neoplasias
19.
Anticancer Res ; 40(8): 4387-4394, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32727767

RESUMO

BACKGROUND/AIM: Intensive trimodal therapy is needed for locally advanced esophageal squamous cell carcinoma (ESCC). The prediction of recurrence is especially required for patients with pathological residual tumors in the resected primary sites and/or lymph nodes [non-pathological complete response (pCR)] who have a high possibility of recurrence after trimodal therapy. We aimed to determine the risk factors for cancer recurrence in ESCC patients diagnosed with non-pCR after trimodal therapy. PATIENTS AND METHODS: We evaluated the risk factors for recurrence-free survival (RFS) using the multivariate Cox proportional hazards analysis, based on data from 105 ESCC patients diagnosed with non-pCR after neoadjuvant chemoradiotherapy followed by esophagectomy. RESULTS: Univariate analysis revealed that RFS was significantly associated with postoperative complications, pathological T, N, M stage after therapy (ypT, ypN, ypM), tumor differentiation, lymphovascular invasion (LVI), and pathological response of the primary tumor. Subsequent multivariate analysis revealed postoperative complications ypN, tumor differentiation, and LVI as independent variables for RFS. The RFSs significantly differed between patients with and without these risk factors. CONCLUSION: Severe postoperative complications, ypN 2/3, poor tumor differentiation, and LVI were significantly associated with poor RFS. These factors may be used as prognostic factors in patients with non-pCR after trimodal therapy.


Assuntos
Quimiorradioterapia/métodos , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas do Esôfago/terapia , Esofagectomia/métodos , Recidiva Local de Neoplasia/diagnóstico , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Terapia Neoadjuvante , Estadiamento de Neoplasias , Fatores de Risco , Análise de Sobrevida , Resultado do Tratamento
20.
Ann Surg ; 272(2): 311-318, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32675544

RESUMO

OBJECTIVE: We aimed to determine whether tumor metabolism could be prognostic of cure in L-EAC patients who receive definitive chemoradiation. SUMMARY BACKGROUND DATA: Patients with inoperable localized esophageal adenocarcinoma (L-EAC) often receive definitive chemoradiation; however, biomarkers and/or imaging variables to prognosticate cure are missing. METHODS: Two hundred sixty-six patients with L-EAC who had chemoradiation but not surgery were analyzed from the prospectively maintained EAC databases in the Department of Gastrointestinal Medical Oncology at The University of Texas MD Anderson Cancer Center (Texas, USA) between March 2002 and April 2015. Maximum standardized uptake value (SUVmax) and total lesion glycolysis (TLG) from the positron emission tomography data were evaluated. RESULTS: Of 266 patients, 253 (95%) were men; the median age was 67 years (range 20-91 yrs) and 153 had poorly differentiated L-EAC. The median SUVmax was 10.3 (range 0-87) and the median TLG was 85.7 (range 0-3227). Both SUVmax and TLG were higher among those with: tumors >5 cm in length, high clinical stage, and high tumor and node categories by TNM staging (all P < 0.0001). Of 234 patients evaluable for cure, 60 (25.6%) achieved cure. In the multivariable logistic regression model, low TLG (but not low SUVmax) was associated with cure (continuous TLG value: odds ratio 0.70, 95% confidence interval (CI) 0.54-0.92). TLG was quantified into 4 quartile categorical variables; first quartile (Q1; <32), second quartile (Q2; 32.0-85.6), third quartile (Q3; 85.6-228.4), and fourth quartile (Q4; >228.4); the cure rate was only 10.3% in Q4 and 5.1% in Q3 but increased to 28.8% in Q2, and 58.6% in Q1. The cross-validation resulted in an average accuracy of prediction score of 0.81 (95% CI, 0.75-0.86). CONCLUSIONS: In this cross-validated model, 59% of patients in the 1st quartile were cured following definitive chemoradiation. Baseline TLG could be pursued as one of the tools for esophageal preservation.


Assuntos
Adenocarcinoma/patologia , Adenocarcinoma/terapia , Quimiorradioterapia/métodos , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/terapia , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Institutos de Câncer , Estudos de Coortes , Bases de Dados Factuais , Intervalo Livre de Doença , Neoplasias Esofágicas/diagnóstico por imagem , Neoplasias Esofágicas/mortalidade , Feminino , Seguimentos , Glicólise/efeitos dos fármacos , Glicólise/efeitos da radiação , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Estudos Retrospectivos , Medição de Risco , Estatísticas não Paramétricas , Análise de Sobrevida , Texas , Fatores de Tempo , Resultado do Tratamento , Carga Tumoral/efeitos dos fármacos , Carga Tumoral/efeitos da radiação
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