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1.
Lancet Child Adolesc Health ; 5(8): 546-558, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34214481

RESUMO

BACKGROUND: A standardised approach to treatment of paediatric non-rhabdomyosarcoma soft tissue sarcomas (NRSTS), which account for about 4% of childhood cancers, is still lacking. We report the results of the NRSTS 2005 protocol developed specifically by the European Pediatric Soft Tissue Sarcoma Study Group (EpSSG) to determine a risk-adapted multimodal standard of care for this group of tumours. METHODS: The EpSSG NRSTS 2005 study included two prospective, non-randomised, historically controlled trials (one on localised adult-type NRSTS and the other on localised synovial sarcoma) done at 100 academic centres and hospitals in 14 countries. Patients younger than 21 years with a pathologically proven diagnosis of synovial sarcoma or an adult-type NRSTS, no evidence of metastatic disease, no previous treatment other than primary surgery, and diagnostic specimens available for pathological review were included. Patients were stratified by surgical stage, tumour size, nodal involvement, tumour grade (for adult-type NRSTS), and tumour site (for synovial sarcoma). Patients were then divided into four treatment groups: surgery alone, adjuvant radiotherapy, adjuvant chemotherapy (with or without radiotherapy), or neoadjuvant chemotherapy (with or without radiotherapy). The main chemotherapy regimen was ifosfamide (3·0 g/m2 intravenously per day for 3 days) plus doxorubicin (37·5 mg/m2 intravenously per day for 2 days); only ifosfamide (3·0 g/m2 intravenously per day for 2 days) was given concomitantly with radiotherapy (delivered with three-dimensional conformal external beam technique, using conventional fractionation [1·8 daily fractions, 5 days per week] at a dose of 50·4 Gy or 54·0 Gy, to a maximum of 59·4 Gy). The number of chemotherapy cycles ranged from three to seven depending on the stage of the disease. The primary outcomes were event-free survival and overall survival. This study has been completed, and is registered under EudraCT, 2005-001139-31. FINDINGS: Between May 31, 2005, and Dec 31, 2016, 1321 patients were enrolled, of whom 569 (206 with synovial sarcoma and 363 with adult-type NRSTS), with a median age of 12·6 years (IQR 8·2-14·9), were included in this analysis. With a median follow-up of 80·0 months (IQR 54·3-111·3) for the 467 patients alive, 5-year event-free survival was 73·7% (95% CI 69·7-77·2) and 5-year overall survival was 83·8% (95% CI 80·3-86·7). 5-year event-free survival was 91·4% (95% CI 87·0-94·4) and 5-year overall survival was 98·1% (95% CI 95·0-99·3) in the surgery alone group (n=250); 75·5% (46·9-90·1) and 88·2% (60·6-96·9) in the adjuvant radiotherapy group (n=17); 65·6% (54·8-74·5) and 75·8% (65·3-83·5) in the adjuvant chemotherapy group (n=93); and 56·4% (49·3-63·0) and 70·4% (63·3-76·4) in the neoadjuvant chemotherapy group (n=209). Reported severe adverse events included one case of generalised seizures (probably related to ifosfamide) and six cases of secondary tumours. INTERPRETATION: Findings from the EpSSG NRSTS 2005 study help to define the risk-adapted standard of care for this patient population. Adjuvant treatment can be safely omitted in the low-risk population (classified here as the surgery alone group). Improving the outcome for patients with high-risk, initially resected adult-type NRSTS and those with initially unresectable disease remains a major clinical challenge. FUNDING: Fondazione Città della Speranza.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doxorrubicina/administração & dosagem , Ifosfamida/administração & dosagem , Sarcoma , Neoplasias de Tecidos Moles , Adolescente , Quimiorradioterapia Adjuvante , Criança , Intervalo Livre de Doença , Europa (Continente) , Feminino , Humanos , Masculino , Estadiamento de Neoplasias , Guias de Prática Clínica como Assunto/normas , Estudos Prospectivos , Sarcoma/tratamento farmacológico , Sarcoma/radioterapia , Sarcoma/cirurgia , Sarcoma Sinovial/tratamento farmacológico , Sarcoma Sinovial/radioterapia , Sarcoma Sinovial/cirurgia , Neoplasias de Tecidos Moles/tratamento farmacológico , Neoplasias de Tecidos Moles/radioterapia , Neoplasias de Tecidos Moles/cirurgia
2.
Br J Radiol ; 94(1124): 20201088, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34260297

RESUMO

OBJECTIVE: The aim of this study was to compare the clinical efficacy of neoadjuvant chemoradiotherapy (NACRT) combined with postoperative adjuvant XELOX (Oxaliplatin +Capecitabine) chemotherapy and postoperative adjuvant chemotherapy (ACT) with XELOX for local advanced gastric cancer (LAGC). METHODS: In this prospectively randomized trial, we investigated the effect of NACRT combined with postoperative ACT for LAGC. 60 patients were randomly divided into NACRT group and ACT group, with 30 patients in each group. Patients in NACRT group were given three-dimensional conformal radiotherapy (45 Gy/1.8 Gy/f) accompanied by synchronous XELOX of two cycles, followed by surgery, and then postoperative adjuvant XELOX chemotherapy of four cycles was performed. Patients in ACT group received surgery in advance, and then XELOX chemotherapy of six cycles was given. RESULTS: The objective response rate of NACRT was 76.7%. The overall incidence of postoperative complications in NACRT group was not significantly different from that in ACT group (23.1% vs 30.0%, p = 0.560). The 1 year, 2 years, and 3 years progression-free survival (PFS)and overall survival (OS) in NACRT and ACT groups were 80.0% vs 56.7%, 73.3% vs 46.7%, 60.0% vs 33.3%, and 86.7% vs 80.0%, 76.7% vs 66.7%, 63.3% vs 50.0%, respectively. Patients in NACRT group showed a significantly higher R0 resection rate (84.6% vs 56.7%, p = 0.029),lower loco-regional recurrence rate (36.7% vs 11.5%, p = 0.039), longer PFS (p = 0.019) and freedom from locoregional progression(FFLP) (p = 0.004) than patients in ACT group, while there was no difference in OS (p = 0.215) and in toxicity incidence (p > 0.05). CONCLUSIONS: NACRT combined with postoperative adjuvant XELOX chemotherapy can improve R0 resection rate, reduce loco-regional recurrence, prolong PFS and FFLP without increasing the incidence of postoperative complications in patients with LAGC. ADVANCES IN KNOWLEDGE: Compared with postoperative adjuvant chemotherapy, locally advanced gastric cancer patients may benefit from neoadjuvant chemoradiotherapy, and toxicity associated with chemoradiotherapy was tolerant and manageable.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Capecitabina/uso terapêutico , Oxaloacetatos/uso terapêutico , Radioterapia Conformacional , Neoplasias Gástricas/terapia , Quimiorradioterapia Adjuvante , Quimioterapia Adjuvante , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Invasividade Neoplásica , Período Pós-Operatório , Estudos Prospectivos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Resultado do Tratamento
3.
Aging (Albany NY) ; 13(13): 17337-17348, 2021 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-34226296

RESUMO

Adjuvant concurrent chemoradiotherapy (CCRT) is the standard care for patients with resected advanced gastric cancer, but its survival benefits remain undetermined in patients undergoing D2 lymph node dissection (D2 dissection). We evaluated safety and efficacy of adjuvant CCRT with 5-fluorouracil (5-FU) versus chemotherapy alone in 110 gastric cancer patients with D2 dissection treated in Taiwan between January 2009 and January 2013. All the 71 patients receiving adjuvant CCRT were treated with daily infusional 5-FU and radiotherapy. Adjuvant CCRT was associated with higher risks of major hematologic (56.3% vs. 23.8%, p = 0.002) and gastrointestinal (46.9% vs. 14.3%, p = 0.027) toxicities and death (12.5% vs. 0.0%, p = 0.041) in patients above 70 years old, but this was not the case in those ≤70 years of age. Univariate Cox proportional regressions identified adjuvant CCRT as a factor for better overall survival (OS) (hazard ratio [HR]=0.52; 95% confidence interval [CI]: 0.27-0.99) and disease-free survival (DFS) (HR=0.46, 95% CI: 0.24-0.88), but it was not a significant factor for OS or DFS after adjusting for other factors in the multivariate analysis. However, in stratified analyses by age, we found adjuvant CCRT was an independent prognostic factor for better OS (HR=0.07; 95% CI: 0.01-0.38) in patients ≤70 years old, but not in those above 70 years of age. Therefore, it was concluded that age may to be a modifier of the effects of adjuvant CCRT.


Assuntos
Envelhecimento , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/uso terapêutico , Quimiorradioterapia Adjuvante/métodos , Fluoruracila/administração & dosagem , Fluoruracila/uso terapêutico , Neoplasias Gástricas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/efeitos adversos , Quimiorradioterapia Adjuvante/efeitos adversos , Intervalo Livre de Doença , Feminino , Fluoruracila/efeitos adversos , Humanos , Infusões Intravenosas , Excisão de Linfonodo/métodos , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Análise de Sobrevida , Taiwan , Resultado do Tratamento
4.
J Clin Neurosci ; 90: 39-47, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34275579

RESUMO

The optimal timing of adjuvant radiochemotherapy (RCT) in glioblastoma (GBM) patients remains unknown and the paradigm of 'the sooner, the better' has been challenged by many recent publications. In this study, we present unique data on the outcomes of patients with significant treatment delays. The study group consisted of 346 GBM patients (median age 56.8 years) who received surgical treatment (total or subtotal resection) and then underwent adjuvant concurrent RCT at one institution. The main endpoint was overall survival (OS). The Univariate and multivariate Cox Proportional-Hazard Model, log-rank test, and Kaplan-Meier method were used for the analysis. The median OS was 18.7 months and the 5-year overall survival was 8.5%. The median time interval from surgery to RCT was 9.8 weeks. The Cox regression showed that the time interval had no statistically significant impact on OS both in uni- and multivariate analysis. The explorative analysis suggested a positive trend for improved survival for patients in the 1st quartile of the time interval, especially for patients with residual disease or local recurrence prior to RCT, However, considering the 6.9 weeks median interval in the 1st quartile, this subgroup should still be regarded as 'moderate delay' compared with other literature data. The results indicate that the time interval is not a clear prognostic factor in the treatment of GBM. Prospective trials are highly warranted, as data suggest that moderate delays in the initiation of adjuvant treatment might be associated with survival benefit.


Assuntos
Neoplasias Encefálicas/terapia , Quimiorradioterapia Adjuvante/métodos , Glioblastoma/terapia , Procedimentos Neurocirúrgicos/métodos , Tempo para o Tratamento , Adulto , Idoso , Neoplasias Encefálicas/mortalidade , Terapia Combinada/métodos , Feminino , Glioblastoma/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia/tratamento farmacológico , Prognóstico , Modelos de Riscos Proporcionais
5.
Medicine (Baltimore) ; 100(25): e26214, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34160385

RESUMO

ABSTRACT: To investigate the relationship between the changes in circulating CD45RO+T lymphocyte subsets following neoadjuvant therapy for rectal cancer in patients with locally advanced rectal cancer.The clinicopathological data of 185 patients with rectal cancer who received neoadjuvant therapy in the General Surgery Department of Beijing Chaoyang Hospital affiliated to Capital Medical University from June 2015 to June 2017 were analyzed. Venous blood samples were collected 1 week before neoadjuvant therapy and 1 week before surgery, and the expression of CD45RO+T was detected by flow cytometry. The receiver operating characteristic curve analysis was used to determine the optimal cut-off point of CD45RO+ratio. Log-rank test and multivariate Cox regression were used to analyze the overall survival rate (OS) and disease-free survival rate (DFS) associated with CD45RO+ratio.Circulating CD45RO+ratio of 1.07 was determined as the optimal cut-off point and CD45RO+ratio-high was associated with lower tumor regression grade grading (P = .031), T stage (P = .001), and tumor node metastasis (TNM) stage (P = .012). The 3-year DFS and OS rate in the CD45RO+ratio-high group was significantly higher than that in the CD45RO+ratio-low group (89.2% vs 60.1%, P<.001; 94.4% vs 73.2%, P<.001). The multivariate Cox analysis revealed that elevated CD45RO+ratio was an independent factor for better DFS (OR, 0.339; 95% CI, 0.153-0.752; P = .008) and OS (OR, 0.244; 95% CI,0.082-0.726; P = .011).Circulating CD45RO+ratio could predict the tumor regression grade of neoadjuvant therapy for rectal cancer, as well as long-term prognosis. These findings could be used to stratify patients and develop alternative strategies for adjuvant therapy.


Assuntos
Quimiorradioterapia Adjuvante/métodos , Terapia Neoadjuvante/métodos , Recidiva Local de Neoplasia/epidemiologia , Neoplasias Retais/terapia , Subpopulações de Linfócitos T/imunologia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Separação Celular , Colonoscopia , Ciclofosfamida/uso terapêutico , Intervalo Livre de Doença , Doxorrubicina/uso terapêutico , Citometria de Fluxo , Seguimentos , Humanos , Antígenos Comuns de Leucócito/metabolismo , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/imunologia , Estadiamento de Neoplasias , Oxaliplatina/uso terapêutico , Prednisona/uso terapêutico , Período Pré-Operatório , Protectomia , Prognóstico , Radioterapia de Intensidade Modulada , Neoplasias Retais/sangue , Neoplasias Retais/imunologia , Neoplasias Retais/mortalidade , Reto/diagnóstico por imagem , Reto/patologia , Reto/cirurgia , Estudos Retrospectivos , Taxa de Sobrevida , Subpopulações de Linfócitos T/metabolismo , Vindesina/uso terapêutico
6.
Medicine (Baltimore) ; 100(25): e26384, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34160415

RESUMO

RATIONALE: A hormone-active metastatic Hürthle cell thyroid carcinoma (HCTC) and Graves disease (GD) present a therapeutic challenge and is rarely reported. PATIENT CONCERNS: We present a 64-year-old male patient, who had dyspnea and left hip pain lasting 4 months. He had clinical signs of hyperthyroidism and a tumor measuring 9 cm in diameter of the left thyroid lobe, metastatic neck lymph node and metastases in the lungs, mediastinum, and bones. DIAGNOSIS: Laboratory findings confirmed hyperthyroidism and GD. Fine-needle aspiration biopsy and cytological investigation revealed metastases of HCTC in the skull and in the 8th right rib. A CT examination showed a thyroid tumor, metastatic neck lymph node, metastases in the lungs, mediastinum and in the 8th right rib measuring 20 × 5.6 × 4.5 cm, in the left acetabulum measuring 9 × 9 × 3 cm and parietooccipitally in the skull measuring 5 × 4 × 2 cm. Histology after total thyroidectomy and resection of the 8th right rib confirmed metastatic HCTC. INTERVENTIONS: The region of the left hip had been irradiated with concomitant doxorubicin 20 mg once weekly. When hyperthyroidism was controlled with thiamazole, a total thyroidectomy was performed. Persistent T3 hyperthyroidism, most likely caused by TSH-R-stimulated T3 production in large metastasis in the 8th right rib, was eliminated by rib resection. Thereafter, the patient was treated with 3 radioactive iodine-131 (RAI) therapies (cumulative dose of 515 mCi). Unfortunately, the tumor rapidly progressed after treatment with RAI and progressed 10 months after therapy with sorafenib. OUTCOMES: Despite treatment, the disease rapidly progressed and patient died due to distant metastases. He survived for 28 months from diagnosis. LESSONS: Simultaneous hormone-active HCTC and GD is extremely rare and prognosis is dismal. Concomitant external beam radiotherapy and doxorubicin chemotherapy, followed by RAI therapy, prevented the growth of a large metastasis in the left hip in our patient. However, a large metastasis in the 8th right rib presented an unresolved problem. Treatment with rib resection and RAI did not prevent tumor recurrence. External beam radiotherapy and sorafenib treatment failed to prevent tumor growth.


Assuntos
Adenoma Oxífilo/diagnóstico , Doença de Graves/diagnóstico , Neoplasias da Glândula Tireoide/diagnóstico , Adenoma Oxífilo/complicações , Adenoma Oxífilo/secundário , Adenoma Oxífilo/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biópsia por Agulha Fina , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/secundário , Neoplasias Ósseas/terapia , Quimiorradioterapia Adjuvante/métodos , Evolução Fatal , Doença de Graves/complicações , Doença de Graves/terapia , Humanos , Radioisótopos do Iodo/uso terapêutico , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/terapia , Metástase Linfática/diagnóstico , Metástase Linfática/terapia , Masculino , Neoplasias do Mediastino/diagnóstico , Neoplasias do Mediastino/secundário , Neoplasias do Mediastino/terapia , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Glândula Tireoide/diagnóstico por imagem , Glândula Tireoide/patologia , Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/complicações , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/secundário , Neoplasias da Glândula Tireoide/terapia , Tireoidectomia
7.
J Surg Oncol ; 124(5): 810-817, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34159619

RESUMO

BACKGROUND: Despite guideline recommendations, some patients still receive care inappropriate for their clinical stage of disease. Identification of factors that contribute to variation in guideline base care may help eradicate disparities in the treatment of early and locally advanced rectal cancer. METHODS: The American College of Surgeons National Cancer Database from 2010 to 2015 was analyzed with propensity score weighting to identify factors associated with delivery and omission of neoadjuvant guideline-based chemoradiation (GBC) for those with early and locally advanced rectal cancer. RESULTS: Only 74% of patients with rectal cancer received stage-appropriate neoadjuvant chemoradiation; 4544 (88%) of those with early stage disease and 8675 (68%) in locally advanced disease. Chemotherapy and radiotherapy were not planned in 27% and 34% respectively, of those who did not receive GBC. Factors associated with receipt of non-guideline-based neoadjuvant chemoradiation were age >65 years, Medicare insurance, treatment at a community facility, West-South-Central geography, having locally advanced disease, and Charlson-Deyo score >3. Receipt of ideal guideline-based neoadjuvant chemoradiation conferred a survival benefit at 5 years. CONCLUSION: Patient and non-patient factors contribute to disparities in guideline-based delivery of neoadjuvant chemoradiation in the treatment of rectal cancer. Identification of these risk factors are important to help standardize care and improve survival outcomes.


Assuntos
Quimiorradioterapia Adjuvante/mortalidade , Atenção à Saúde/normas , Disparidades em Assistência à Saúde , Terapia Neoadjuvante/mortalidade , Neoplasias Retais/terapia , Idoso , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Prognóstico , Pontuação de Propensão , Neoplasias Retais/etnologia , Neoplasias Retais/patologia , Taxa de Sobrevida
8.
Medicina (Kaunas) ; 57(6)2021 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-34072478

RESUMO

Background and Objectives: In October 2018, the International Federation of Gynecology and Obstetrics (FIGO) revised its classification of advanced stages of cervical cancer. The main points of the classification are as follows: stage IIIC is newly established; pelvic lymph node metastasis is stage IIIC1; and para-aortic lymph node metastasis is stage IIIC2. Currently, in Japan, radical hysterectomy is performed in advanced stages IA2 to IIB of FIGO2014, and concurrent chemoradiotherapy (CCRT) is recommended for patients with positive lymph nodes. However, the efficacy of CCRT is not always satisfactory. The aim of this study was to compare postoperative adjuvant chemotherapy (CT) and postoperative CCRT in stage IIIC1 patients. Materials and Methods: Of the 40 patients who had undergone a radical hysterectomy at Iwate Medical University between January 2011 and December 2016 and were pathologically diagnosed as having positive pelvic lymph nodes, 21 patients in the adjuvant CT group and 19 patients in the postoperative CCRT group were compared. Results: The 5 year survival rates were 77.9% in the CT group and 74.7% in the CCRT group, with no significant difference. There was no significant difference in overall survival or progression-free survival between the two groups. There was no significant difference between CT and CCRT in postoperative adjuvant therapy in the new classification IIIC1 stage. Conclusions: The results of the prospective Japanese Gynecologic Oncology Group (JGOG) 1082 study are pending, but the present results suggest that CT may be a treatment option in rural areas where radiotherapy facilities are limited.


Assuntos
Neoplasias do Colo do Útero , Quimiorradioterapia , Quimiorradioterapia Adjuvante , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Humanos , Japão , Estadiamento de Neoplasias , Estudos Prospectivos , Estudos Retrospectivos , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/terapia
9.
Medicine (Baltimore) ; 100(19): e25778, 2021 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-34106610

RESUMO

RATIONALE: Intracranial yolk sac tumors (YSTs) are rare malignancies with limited treatment options and a dismal prognosis. They are usually managed with surgical resection and chemoradiotherapy. PATIENT CONCERNS: Here, we report a patient with primary YST in the pineal region who achieved long term survival. Despite undergoing treatment, he experienced several recurrences over a 15-year period. DIAGNOSIS: Brain magnetic resonance imaging (MRI) demonstrated the presence of space-occupying lesions in the pineal region and the medial tail of the left lateral ventricle. The tumors were excised, and the histological diagnosis suggested an intracranial YST. INTERVENTIONS: The patient achieved long term survival after combined modality therapy including surgery, stereotactic radiosurgery (SRS)/intensity modulated radiation therapy (IMRT), chemotherapy, and targeted therapy. OUTCOMES: The disease remained stable. However, the patient gave up treatment and passed away in October 2020, with a total survival of about 15 years. LESSONS: To the best of our knowledge, this patient with intracranial YST had received a longer survival compared with other published reports. We summarize previously published reports of intracranial YST and discuss the importance of multidisciplinary treatment. SRS may have a role, as a focal boost to residual tumor after resection or in case of recurrence after conventional radiotherapy, in the multimodality management of intracranial YSTs.


Assuntos
Neoplasias Encefálicas/terapia , Tumor do Seio Endodérmico/terapia , Ventrículos Laterais , Equipe de Assistência ao Paciente , Glândula Pineal , Neoplasias Encefálicas/diagnóstico , Quimiorradioterapia Adjuvante , Tumor do Seio Endodérmico/diagnóstico , Evolução Fatal , Humanos , Masculino , Radiocirurgia , Adulto Jovem
10.
Medicine (Baltimore) ; 100(19): e25862, 2021 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-34106633

RESUMO

RATIONALE: Meningeal melanocytoma is a rare benign melanocytic tumor of the central nervous system. We report for the first time a case of meningeal melanocytoma treated with immunotherapy. PATIENT CONCERNS: A 70-year-old man with no medical history was admitted to the Emergency Room. He suffered from a motor and sensory deficit in his left lower limb and a bilateral upper arm neuralgia. DIAGNOSES: A contrast-enhanced magnetic resonance imaging (MRI) was performed. It showed a C7-T1 bleeding intramedullary tumor. Laminectomy was decided and performed. The results of the pathologic examination showed a melanocytic tumor harboring GNAQ mutation. Meningeal melanocytoma was the final diagnosis. INTERVENTIONS: The patient was treated with 10 radiotherapy sessions and 6 cycles of nivolumab. A year later, the patient experienced neuralgia again with severe pain and an increasing sensory motor deficit. He underwent a second surgery that was incomplete. As the tumor kept growing, he received temozolomide. But the 6th cycle had to be interrupted due to bedsore infection in the hip area. OUTCOMES: Disease progression finally led to the patient's death 3 years after diagnosis. LESSONS: This case report is the first about a patient with meningeal melanocytoma treated with immunotherapy. Treatment based on biomolecular mutations will probably change spinal melanocytoma therapeutic approach in the next few years.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Quimiorradioterapia Adjuvante/métodos , Melanoma/terapia , Neoplasias Meníngeas/terapia , Nivolumabe/uso terapêutico , Idoso , Antineoplásicos Imunológicos/administração & dosagem , Humanos , Laminectomia/métodos , Masculino , Melanócitos/patologia , Melanoma/tratamento farmacológico , Neoplasias Meníngeas/tratamento farmacológico , Nivolumabe/administração & dosagem
11.
Am J Clin Oncol ; 44(7): 301-307, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33979100

RESUMO

BACKGROUND: Trastuzumab prolonged the overall survival in patients with advanced gastric cancer with human epidermal growth factor receptor 2 (HER2) overexpression in combination with chemotherapy. In this phase II open-label prospective study, the tolerability and safety of trastuzumab with chemotherapy, and chemoradiotherapy for curatively resected patients with HER2-positive gastric carcinoma was investigated. METHODS: The patients with HER2-positive gastric, or gastroesophageal junction adenocarcinoma, after gastrectomy plus D2 dissection, were included. They received 3 cycles of oxaliplatin (100 mg/m2 intravenously day 1) plus capecitabine (850 mg/m2 orally days 1 to 14), trastuzumab (8 mg/kg intravenously day 1 in cycle 1, 6 mg/kg thereafter) every 21 days, followed by chemoradiotherapy. Trastuzumab was given for 1 year. RESULTS: Of the 212 patients screened, 35 were eligible, and 34 were treated. The median age was 56 years (minimum to maximum: 35 to 75 y), male patients constituted 73.5% (n=25), and 33 (97.1%) had gastric adenocarcinoma. R0 resection was performed in 30 (88.2%). The majority (26, 61.7%) were in stage III disease. Most of the adverse events were grade I/II, the most frequent grade III side effects were nausea (3, 8.8%), vomiting (3, 8.8%), diarrhea (2, 5.9%), and weight loss (n=2, 5.9%). Two patients died during the first 3 cycles of chemotherapy and chemoradiotherapy; 1 secondary to pulmonary thromboembolism, and the other due to cerebral ischemia. After excluding 2 with early progression and 1 consent withdrawal, of the remaining 31 patients, 28 (90.3%) were able to complete the chemotherapy and chemoradiotherapy part of the trial. After the 25 months follow-up period, 21 patients (61.8%) were alive. Overall survival at 12 and 24 months was 75.0% and 58.0%, while disease-free survival at 12 and 24 months was 65.7% and 55.0%, respectively. CONCLUSIONS: Trastuzumab in combination with capecitabine, oxaliplatin following chemoradiotherapy as the adjuvant therapy for gastric or gastroesophageal junction adenocarcinoma was considered as safe and tolerable. The frequency of HER2 overexpression in curatively resected patients is comparable to that in patients with metastatic disease (trial registration: clinicaltrials.gov the identifier: NCT01748773, December 13, 2012, https://clinicaltrials.gov/ct2/show/NCT01748773).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Gástricas/terapia , Adulto , Idoso , Capecitabina/administração & dosagem , Quimiorradioterapia Adjuvante , Intervalo Livre de Doença , Junção Esofagogástrica/patologia , Feminino , Gastrectomia , Humanos , Masculino , Pessoa de Meia-Idade , Oxaliplatina/administração & dosagem , Receptor ErbB-2/metabolismo , Neoplasias Gástricas/mortalidade , Trastuzumab/administração & dosagem , Resultado do Tratamento
12.
Cancer Sci ; 112(8): 3018-3028, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34009732

RESUMO

Signal regulatory protein alpha (SIRPα) is a type I transmembrane protein that inhibits macrophage phagocytosis of tumor cells upon interaction with CD47, and the CD47-SIRPα pathway acts as an immune checkpoint factor in cancers. This study aims to clarify the clinical significance of SIRPα expression in esophageal squamous cell carcinoma (ESCC). First, we assessed SIRPα expression using RNA sequencing data of 95 ESCC tissues from The Cancer Genome Atlas (TCGA) and immunohistochemical analytic data from our cohort of 131 patients with ESCC. Next, we investigated the correlation of SIRPα expression with clinicopathological factors, patient survival, infiltration of tumor immune cells, and expression of programmed cell death-ligand 1 (PD-L1). Overall survival was significantly poorer with high SIRPα expression than with low expression in both TCGA and our patient cohort (P < .001 and P = .027, respectively). High SIRPα expression was associated with greater depth of tumor invasion (P = .0017). Expression of SIRPα was also significantly correlated with the tumor infiltration of M1 macrophages, M2 macrophages, CD8+ T cells, and PD-L1 expression (P < .001, P < .001, P = .03, and P < .001, respectively). Moreover, patients with SIRPα/PD-L1 coexpression tended to have a worse prognosis than patients with expression of either protein alone or neither. Taken together, SIRPα indicates poor prognosis in ESCC, possibly through inhibiting macrophage phagocytosis of tumor cells and inducing suppression of antitumor immunity. Signal regulatory protein alpha should be considered as a potential therapeutic target in ESCC, especially if combined with PD-1-PD-L1 blockade.


Assuntos
Antígenos de Diferenciação/genética , Antígenos de Diferenciação/metabolismo , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas do Esôfago/terapia , Perfilação da Expressão Gênica/métodos , Receptores Imunológicos/genética , Receptores Imunológicos/metabolismo , Regulação para Cima , Idoso , Quimiorradioterapia Adjuvante , Quimioterapia Adjuvante , Estudos de Coortes , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/metabolismo , Esofagectomia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Prognóstico , Estudos Retrospectivos , Análise de Sequência de RNA , Análise de Sobrevida , Resultado do Tratamento
13.
Cancer Sci ; 112(7): 2895-2904, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33931909

RESUMO

Several therapeutic regimens, including neoadjuvant chemoradiation therapy (NACRT), have been reported to serve as anticancer immune effectors. However, there remain insufficient data regarding the immune response after NACRT in pancreatic ductal adenocarcinoma (PDAC) patients. Data from 40 PDAC patients that underwent surgical resection after NACRT (NACRT group) and 30 PDAC patients that underwent upfront surgery (US group) were analyzed to examine alterations in immune cell counts/distribution using a multiplexed fluorescent immunohistochemistry system. All immune cells were more abundant in the cancer stroma than in the cancer cell nest regardless of preoperative therapy. Although the stromal counts of CD4+ T cells, CD20+ B cells, and Foxp3+ T cells in the NACRT group were drastically decreased in comparison with those of the US group, counts of these cell types in the cancer cell nest were not significantly different between the two groups. In contrast, CD204+ macrophage counts in the cancer stroma were similar between the NACRT and US groups, while those in the cancer cell nests were significantly reduced in the NACRT group. Following multivariate analysis, only a high CD204+ macrophage count in the cancer cell nest remained an independent predictor of shorter relapse-free survival (odds ratio = 2.37; P = .033). NACRT for PDAC decreased overall immune cell counts, but these changes were heterogeneous within the cancer cell nests and cancer stroma. The CD204+ macrophage count in the cancer cell nest is an independent predictor of early disease recurrence in PDAC patients after NACRT.


Assuntos
Carcinoma Ductal Pancreático/terapia , Quimiorradioterapia Adjuvante , Imunidade Celular , Neoplasias Pancreáticas/terapia , Microambiente Tumoral/imunologia , Idoso , Antígenos CD20 , Linfócitos B/imunologia , Contagem de Linfócito CD4 , Carcinoma Ductal Pancreático/imunologia , Carcinoma Ductal Pancreático/cirurgia , Feminino , Fatores de Transcrição Forkhead/imunologia , Humanos , Imuno-Histoquímica/métodos , Contagem de Linfócitos , Macrófagos/imunologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Terapia Neoadjuvante/métodos , Recidiva Local de Neoplasia/imunologia , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/cirurgia , Cuidados Pré-Operatórios
14.
Cancer Med ; 10(10): 3231-3239, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33934525

RESUMO

BACKGROUND: Only high-risk tumors with extranodal extension (ENE) and/or positive surgical margins (PSM) benefit from adjuvant therapy (AT) with concurrent chemoradiation (CRT) compared to radiation therapy (RT) in locally advanced head and neck squamous cell carcinoma (HNSCC). Optimal treatment for intermediate-risk tumors remains controversial. We categorized patients based on their surgical pathologic risk factors and described AT treatment patterns and associated survival outcomes. METHODS: Patients were identified from CHANCE, a population-based study, and risk was classified based on surgical pathology review. High-risk patients (n = 204) required ENE and/or PSM. Intermediate-risk (n = 186) patients had pathological T3/T4 disease, perineural invasion (PNI), lymphovascular invasion (LVI), or positive lymph nodes without ENE. Low-risk patients (n = 226) had none of these features. RESULTS: We identified 616 HPV-negative HNSCC patients who received primary surgical resection with neck dissection. High-risk patients receiving AT had favorable OS (HR 0.50, p = 0.013) which was significantly improved with the addition of chemotherapy compared to RT alone (HR 0.47, p = 0.021). When stratified by node status, the survival benefit of AT in high-risk patients persisted only among those who were node-positive (HR: 0.17, p < 0.0005). On the contrary, intermediate-risk patients did not benefit from AT (HR: 1.26, p = 0.380) and the addition of chemotherapy was associated with significantly worse OS compared to RT (HR: 1.76, p = 0.046). CONCLUSION: In high-risk patients, adjuvant chemoradiotherapy improved OS compared to RT alone. The greatest benefit was in node-positive cases. In intermediate-risk patients, the addition of chemotherapy to RT increased mortality risk and therefore should only be used cautiously in these patients.


Assuntos
Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Idoso , Quimiorradioterapia Adjuvante/métodos , Terapia Combinada/métodos , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Linfonodos/patologia , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Esvaziamento Cervical/métodos , Estadiamento de Neoplasias/métodos , Infecções por Papillomavirus/patologia , Radioterapia Adjuvante/métodos , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
15.
Lancet Oncol ; 22(7): e314-e326, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34048686

RESUMO

There is no universally accepted instrument to use as a validated surrogate endpoint for overall survival in phase 2 and phase 3 multimodal rectal cancer trials using chemoradiotherapy. Efforts are hampered by the inaccuracy of clinical TNM staging, the variability of indications for neoadjuvant treatment, and diverse definitions of tumour regression grade. Pathological complete response is commonly used, but fails to capture information from the majority of patients. The neoadjuvant rectal score categorises response and downstaging from the entire trial population to identify whether or not a novel treatment group in a chemoradiation trial is superior by predicting overall survival outcomes. Additionally, the neoadjuvant rectal score assesses the difference between initial clinical and pathological T stage and the presence or absence of nodal involvement after treatment. The neoadjuvant rectal score has been conceptually, but incompletely, statistically validated by two independent trial datasets. However, a fundamental weakness of the score is that no preoperative phase 3 trials in locally advanced rectal cancer in the past 20 years have provided a significant benefit in overall survival to statistically validate the neoadjuvant rectal score as a surrogate endpoint for overall survival. We review the robustness, practical value, applicability, generalisability, advantages, and disadvantages of the neoadjuvant rectal score as a surrogate endpoint for overall survival and recommend how this score could be improved and be acceptable as a standard endpoint in studies investigating neoadjuvant chemotherapy and chemoradiation in patients with rectal cancer.


Assuntos
Quimiorradioterapia Adjuvante , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Determinação de Ponto Final , Terapia Neoadjuvante , Neoplasias Retais/terapia , Projetos de Pesquisa , Quimiorradioterapia Adjuvante/efeitos adversos , Quimiorradioterapia Adjuvante/mortalidade , Progressão da Doença , Intervalo Livre de Doença , Humanos , Terapia Neoadjuvante/efeitos adversos , Terapia Neoadjuvante/mortalidade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Neoplasias Retais/mortalidade , Neoplasias Retais/patologia , Medição de Risco , Fatores de Risco , Fatores de Tempo
16.
Nat Commun ; 12(1): 3199, 2021 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-34045463

RESUMO

In patients with metastatic cancer, spatial heterogeneity of somatic alterations may lead to incomplete assessment of a cancer's mutational profile when analyzing a single tumor biopsy. In this study, we perform sequencing of cell-free DNA (cfDNA) and distinct metastatic tissue samples from ten rapid autopsy cases with pre-treated metastatic cancer. We show that levels of heterogeneity in genetic biomarkers vary between patients but that gene expression signatures representative of the tumor microenvironment are more consistent. Across nine patients with plasma samples available, we are able to detect 62/62 truncal and 47/121 non-truncal point mutations in cfDNA. We observe that mutation clonality in cfDNA is correlated with the number of metastatic lesions in which the mutation is detected and use this result to derive a clonality threshold to classify truncal and non-truncal driver alterations with reasonable specificity. In contrast, mutation truncality is more often incorrectly assigned when studying single tissue samples. Our results demonstrate the utility of a single cfDNA sample relative to that of single tissue samples when treating patients with metastatic cancer.


Assuntos
Autopsia/métodos , DNA Tumoral Circulante/genética , Análise Mutacional de DNA/métodos , Neoplasias/diagnóstico , Microambiente Tumoral/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/genética , Quimiorradioterapia Adjuvante , Estudos de Coortes , Variações do Número de Cópias de DNA , Feminino , Heterogeneidade Genética , Humanos , Masculino , Terapia Neoadjuvante , Neoplasias/sangue , Neoplasias/patologia , Neoplasias/terapia , Mutação Puntual , RNA-Seq , Valores de Referência , Sensibilidade e Especificidade , Análise Espacial , Fatores de Tempo , Sequenciamento Completo do Exoma
17.
Surg Clin North Am ; 101(3): 453-465, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34048765

RESUMO

Trimodality therapy, or the use of concurrent chemoradiation followed by surgery, is the cornerstone of contemporary management of esophageal cancer. This article discusses the landmark trials and most current data to understand the concepts, applications, and outcomes from trimodality therapy in locally advanced esophageal cancer.


Assuntos
Adenocarcinoma/terapia , Carcinoma de Células Escamosas/terapia , Quimiorradioterapia Adjuvante , Neoplasias Esofágicas/terapia , Esofagectomia , Terapia Neoadjuvante , Humanos , Resultado do Tratamento
18.
Surg Clin North Am ; 101(3): 483-488, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34048767

RESUMO

Consolidation therapy describes dose intensification strategies or additional treatment performed following completion of the primary regimen. In the case of esophageal cancer, this applies to cases of potentially persistent disease after definitive multi-modality therapy, including surgery. Consolidation should also be considered for patients initially planned to undergo surgery after neoadjuvant therapy, but for any reason elected a nonoperative strategy during treatment. With the advent of targeted therapy and immunotherapy, additional options may be available for consolidation in the future.


Assuntos
Quimiorradioterapia Adjuvante , Quimioterapia de Consolidação/métodos , Neoplasias Esofágicas/terapia , Esofagectomia , Terapia Neoadjuvante , Humanos , Resultado do Tratamento
19.
Medicine (Baltimore) ; 100(21): e26081, 2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34032742

RESUMO

RATIONALE: Hepatocellular carcinoma (HCC) with inferior vena cava tumor thrombus (IVCTT) is traditionally considered an advanced-stage cancer with a poor prognosis. There is no standard treatment for patients diagnosed as HCC with IVCTT. PATIENT CONCERNS: A 52-year-old man was admitted to our hospital because of suspected hepatic mass during a health examination. DIAGNOSES: Computed tomography (CT) showed a hepatic mass approximately 4.3 cm × 6.3 cm in size located in segment VII of the liver, with thrombus in the inferior vena cava. The mass exhibited a pattern of early enhancement and washout on contrast-enhanced CT. Alpha-fetoprotein was 614.1 ng/mL (normal value, <8 ng/mL). The preoperative diagnosis was HCC with IVCTT. INTERVENTIONS: Two months after stereotactic body radiotherapy combined with sorafenib therapy, a planned open anatomical resection of the right posterior lobe of the liver was performed. OUTCOMES: The patient is alive without disease 12 months after surgery, and the level of alpha-fetoprotein is normal. LESSONS: The patient diagnosed as HCC with IVCTT was successfully treated by stereotactic body radiotherapy combined with molecularly targeted drugs followed by surgical treatment. If confirmed in future studies, this would suggest a promising strategy for the management of HCC with IVCTT.


Assuntos
Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/terapia , Trombose Venosa/terapia , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patologia , Quimiorradioterapia Adjuvante/métodos , Hepatectomia , Humanos , Fígado/irrigação sanguínea , Fígado/diagnóstico por imagem , Fígado/patologia , Fígado/cirurgia , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Invasividade Neoplásica , Radiocirurgia , Sorafenibe/uso terapêutico , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Veia Cava Inferior/diagnóstico por imagem , Veia Cava Inferior/patologia , Trombose Venosa/diagnóstico , Trombose Venosa/etiologia
20.
Medicine (Baltimore) ; 100(18): e24480, 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-33950913

RESUMO

ABSTRACT: To explore the risk factors of lung metastasis in patients after laparoscopic radical hysterectomy (LRH) of cervical cancer (CC).The clinical data of CC patients with clinical stage of IA1-IIA2 diagnosed in our hospital from April 2007 to October 2015 were collected. According to the situation of metastasis, the patients were divided into lung metastasis (n = 73) and non-lung metastasis group (n = 2076). The clinical data were compared between 2 groups, and logistic stepwise regression model was used to analyze the risk factors of lung metastasis in patients with CC after LRH.The incidence of lung metastasis after LRH of CC was 3.39%, and 67.13% of patients with lung metastases had no obvious clinical symptoms. 15.06% patients had lung metastasis in the first year, 38.35% in the second year, 43.83% in the third year and later. The postoperative lung metastasis of CC was related to tumor diameter (P < .001), pathological type (P < .001), interstitial invasion depth (P < .001), pelvic lymph node metastasis (PLNM, P < .001), vascular tumor thrombus (P = .011), tumor uterine invasion (P = .002), and abnormal preoperative tumor markers (P = .015). However, it was not related to age, clinical stage, tumor growth pattern, tumor differentiation, and para-aortic lymph node metastasis (P > .05). Logistic regression analysis revealed non-squamous cell carcinoma (P = .022), tumor diameter ≥4 cm (P = .008), interstitial invasion depth >2/3 (P = .003), PLNM (P = .007), and tumor uterine invasion (P = .037) is an independent risk factor for lung metastasis after LRH of CC.Non-squamous cell carcinoma, tumor diameter ≥4 cm, tumor interstitial invasion depth >2/3, PLNM, and tumor uterine invasion are independent risk factors for lung metastasis after LRH of CC.


Assuntos
Carcinoma/epidemiologia , Histerectomia/métodos , Laparoscopia , Neoplasias Pulmonares/epidemiologia , Neoplasias do Colo do Útero/terapia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma/prevenção & controle , Carcinoma/secundário , Colo do Útero/patologia , Colo do Útero/cirurgia , Quimiorradioterapia Adjuvante/métodos , Feminino , Seguimentos , Humanos , Incidência , Neoplasias Pulmonares/prevenção & controle , Neoplasias Pulmonares/secundário , Invasividade Neoplásica , Estadiamento de Neoplasias , Período Pós-Operatório , Radioterapia Conformacional , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Carga Tumoral , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/patologia
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