Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 11.099
Filtrar
1.
Cancer Epidemiol Biomarkers Prev ; 31(7): 1466-1472, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35511739

RESUMO

BACKGROUND: A previous genome-wide association study identified several loci with genetic variants associated with prostate cancer survival time in two cohorts from Sweden. Whether these variants have an effect in other populations or if their effect is homogenous across the course of disease is unknown. METHODS: These variants were genotyped in a cohort of 1,298 patients. Samples were linked with age, PSA level, Gleason score, cancer stage at surgery, and times from surgery to biochemical recurrence to death from prostate cancer. SNPs rs2702185 and rs73055188 were tested for association with prostate cancer-specific survival time using a multivariate Cox proportional hazard model. SNP rs2702185 was further tested for association with time to biochemical recurrence and time from biochemical recurrence to death with a multi-state model. RESULTS: SNP rs2702185 at SMG7 was associated with prostate cancer-specific survival time, specifically the time from biochemical recurrence to prostate cancer death (HR, 2.5; 95% confidence interval, 1.4-4.5; P = 0.0014). Nine variants were in linkage disequilibrium (LD) with rs2702185; one, rs10737246, was found to be most likely to be functional based on LD patterns and overlap with open chromatin. Patterns of open chromatin and correlation with gene expression suggest that this SNP may affect expression of SMG7 in T cells. CONCLUSIONS: The SNP rs2702185 at the SMG7 locus is associated with time from biochemical recurrence to prostate cancer death, and its LD partner rs10737246 is predicted to be functional. IMPACT: These results suggest that future association studies of prostate cancer survival should consider various intervals over the course of disease.


Assuntos
Proteínas de Transporte , Neoplasias da Próstata , Proteínas de Transporte/genética , Cromatina , Estudo de Associação Genômica Ampla , Humanos , Masculino , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/mortalidade , Polimorfismo de Nucleotídeo Único , Antígeno Prostático Específico , Prostatectomia , Neoplasias da Próstata/genética , Neoplasias da Próstata/mortalidade
2.
BMC Cancer ; 22(1): 270, 2022 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-35287627

RESUMO

PURPOSE: To evaluate the efficacy and safety of transarterial chemoembolization (TACE) combined with camrelizumab (hereafter, TACE-camrelizumab) in the treatment of patients with recurrent hepatocellular carcinoma (R-HCC) after curative resection. PATIENTS AND METHODS: R-HCC patients who underwent TACE plus camrelizumab or TACE-alone from January 2016 to August 2021 were retrospectively evaluated. Patients were assessed for tumor response, progression-free survival, survival rates and adverse events. RESULTS: Seventy-one patients were included in this study, including 20 patients in the TACE- camrelizumab group and 51 patients in the TACE-alone group. The objective response rate was 56.9% in the TACE-alone group and 40% in the TACE-camrelizumab group at 3 months (P = 0.201). The disease control rates were 84.3% in TACE-alone group and 80% in TACE-camrelizumab group at 3 months (P = 0.663). The progression-free survival (PFS) of the TACE-alone group was slightly longer than those of the TACE- camrelizumab group (9 months vs. 6 months). However, there were no statistically significant differences in the median PFS (P = 0.586). Similarly, there were no significant differences in the half-year and one-year survival rates (P = 0.304, P = 0.430). Multivariate analysis revealed that Neutrophil-to-lymphocyte ratio (NLR) was associated with PFS significantly. 75% patients developed at least one type of AEs related to camrelizumab in TACE-camrelizumab group, and no patients developed severe AEs. CONCLUSION: Comparing with TACE-Alone, the efficacy of TACE-camrelizumab for patients with R-HCC was similar. Meanwhile, the results of this study also indicated that TACE is still a better choice for patients with R-HCC.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Hepatectomia , Neoplasias Hepáticas/terapia , Carcinoma Hepatocelular/mortalidade , Terapia Combinada , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/terapia , Período Pós-Operatório , Taxa de Sobrevida , Resultado do Tratamento
3.
Clin Cancer Res ; 28(18): 4105-4111, 2022 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-35294527

RESUMO

PURPOSE: This prospective nationwide cohort study aimed to investigate desmoid-type fibromatosis (DF) outcomes, focusing on the prognostic value of CTNNB1 mutations. EXPERIMENTAL DESIGN: ALTITUDES (NCT02867033) was a nationwide prospective cohort study of DF diagnosed between January 2016 and December 2020. At diagnosis, CTNNB1 molecular alterations were identified using next-generation sequencing or Sanger sequencing. The primary endpoint was event-free survival (EFS; progression, relapse, or death). We enrolled 628 patients managed by active surveillance, surgical resection, or systemic treatment as first-line therapy. RESULTS: Overall, 516 (82.2%) patients [368 females (71.3%), median age 40.3 years (range, 1-89)] were eligible for analysis. In 435 (84.3%) cases, there was one CTNNB1 molecular alteration: p.T41A, p.S45F, or p.S45P. The first-line management was active surveillance in 352 (68.2%), surgical resection in 120 (23.3%), and systemic treatments in 44 (8.5%) patients. CTNNB1 mutation distribution was similar across the three therapeutic groups. The median follow-up period was 24.7 (range, 0.4-59.7) months. The estimated 3-year EFS rate was 66.2% [95% confidence interval (CI), 60.5%-71.2%]. DF harboring p.S45F was significantly associated with male sex (P = 0.03), non-abdominal wall sites (P = 0.05), pain (P = 0.007), and large tumor size (P = 0.025). CTNNB1 p.S45F mutation was not significantly associated with EFS, either in univariate (HR, 1.06; 95% CI, 0.65-1.73; P = 0.81) or in multivariate analysis (HR, 0.91; 95% CI, 0.55-1.49; P = 0.71). CONCLUSIONS: We found that CTNNB1 mutation profile was associated with unfavorable prognostic factors but was not a prognostic factor for EFS. See related commentary by Greene and Van Tine, p. 3911.


Assuntos
Fibromatose Agressiva , Adulto , Estudos de Coortes , Feminino , Fibromatose Agressiva/diagnóstico , Fibromatose Agressiva/genética , Fibromatose Agressiva/patologia , Humanos , Masculino , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/mortalidade , Prognóstico , Estudos Prospectivos , beta Catenina/genética
4.
PLoS One ; 17(2): e0263247, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35130287

RESUMO

A recent study suggested that proton pump inhibitor (PPI) use in patients with advanced non-small-cell lung cancer (NSCLC) receiving immune checkpoint inhibitors (ICIs) was associated with poor clinical outcomes. However, the clinical impact of PPI use on the outcome of patients receiving ICIs for postoperative recurrent NSCLC is unknown. The outcomes of 95 patients with postoperative recurrence of NSCLC receiving ICIs at 3 medical centers in Japan were analyzed. We conducted adjusted Kaplan-Meier survival analyses with the log-rank test, a Cox proportional hazards regression analysis, and a logistic regression analysis using inverse probability of treatment weighting (IPTW) to minimize the bias arising from the patients' backgrounds. The IPTW-adjusted Kaplan-Meier curves revealed that the progression-free survival (PFS), but not the overall survival (OS), was significantly longer in patients who did not receive PPIs than in those who did receive them. The IPTW-adjusted Cox regression analysis revealed that PPI use was an independent poor prognostic factor for the PFS and OS. Furthermore, in the IPTW-adjusted logistic regression analysis, PPI non-use was an independent predictor of disease control. In this multicenter and retrospective study, PPI use was associated with poor clinical outcomes in patients with postoperative recurrence of NSCLC who were receiving ICIs. PPIs should not be prescribed indiscriminately to patients with postoperative recurrence of NSCLC who intend to receive ICIs. These findings should be validated in a future prospective study.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Inibidores de Checkpoint Imunológico/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Inibidores da Bomba de Prótons/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Quimioterapia Adjuvante , Estudos Transversais , Quimioterapia Combinada , Feminino , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Japão/epidemiologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Complicações Pós-Operatórias/tratamento farmacológico , Período Pós-Operatório , Inibidores da Bomba de Prótons/efeitos adversos , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
5.
Clin Cancer Res ; 28(3): 498-506, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-35105718

RESUMO

PURPOSE: Previously, clinical trials of experimental virotherapy for recurrent glioblastoma multiforme (GBM) demonstrated that inoculation with a conditionally replication-competent Δγ134.5 oncolytic herpes simplex virus (oHSV), G207, was safe. Following the initial safety study, a phase Ib trial enrolled 6 adult patients diagnosed with GBM recurrence from which tumor tissue was banked for future studies. PATIENTS AND METHODS: Here, we analyzed tumor RNA sequencing (RNA-seq) data obtained from pre- and posttreatment (collected 2 or 5 days after G207 injection) biopsies from the phase Ib study patients. RESULTS: Using a Spearman rank-order correlation analysis, we identified approximately 500 genes whose expression pattern correlated with survival duration. Many of these genes were enriched for the intrinsic IFN-mediated antiviral and adaptive immune functional responses, including immune cell chemotaxis and antigen presentation to T-cells. Furthermore, we show that the expression of several T-cell-related genes was highest in the patient with the longest survival after G207 inoculation. CONCLUSIONS: Our data support that the oHSV-induced type I IFN production and the subsequent recruitment of an adaptive immune response differed between enrolled patients and showed association with survival duration in patients with recurrent malignant glioma after treatment with an early generation oHSV.


Assuntos
Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Ensaios Clínicos Fase I como Assunto , Perfilação da Expressão Gênica/métodos , Glioblastoma/genética , Glioblastoma/terapia , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/terapia , Terapia Viral Oncolítica/métodos , Vírus Oncolíticos , RNA Neoplásico/genética , Simplexvirus , Adulto , Idoso , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/mortalidade , Feminino , Glioblastoma/imunologia , Glioblastoma/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Taxa de Sobrevida
6.
Breast Cancer Res Treat ; 192(3): 629-637, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35113257

RESUMO

PURPOSE: Breast cancer is increasing around the globe, including Asia. We aimed to examine the survival and risk of contralateral breast cancer (CBC) in Asian breast cancer patients with BRCA mutations. METHODS: A total of 128 breast cancer patients with germline BRCA mutations and 4,754 control breast cancer patients were enrolled. Data on clinical-pathologic characteristics, survival, and CBC were collected from the medical record. The rates of survival and CBC were estimated by Kaplan-Meier method. RESULTS: The mean age of onset in BRCA mutation carriers was significantly younger than control patients (BRCA vs. Non-BRCA: 43.9 vs. 53.2 years old). BRCA mutation carriers had a higher proportion of triple-negative breast cancer (TNBC) (52%) than control patients (12%, p < 0.001). The risk of CBC was significantly higher in BRCA mutation patients than in control cases (hazard ratio (HR) = 3.95, 95% CI 2.71-5.75); when stratified by genotype, the HRs (95%CI) were 4.84 (3.00-7.82) for BRCA1 and 3.13 (1.78-5.49) for BRCA2 carriers, respectively. Moreover, BRCA1 mutation patients with triple-negative breast cancer (TNBC) as their first breast cancer had the highest risk of CBC (HR = 5.55, 95% CI 3.29-9.34). However, we did not observe any differences in relapse-free survival and overall survival between mutation carriers and control patients. CONCLUSION: Our study suggest that BRCA patients had a significantly higher risk of developing CBC, particularly for BRCA1 mutation carriers with TNBC as the first breast cancer.


Assuntos
Proteína BRCA1 , Proteína BRCA2 , Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Adulto , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/genética , Feminino , Mutação em Linhagem Germinativa , Heterozigoto , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/mortalidade , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/mortalidade
7.
Sci Rep ; 12(1): 1845, 2022 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-35115612

RESUMO

Carbon ion radiotherapy (CIRT) has garnered interest for the treatment of locoregional rectal cancer recurrence. No study has compared CIRT and X-ray radiotherapy (XRT) for reirradiation (reRT) in such cases. We analyzed and compared the clinical outcomes such as local control, overall survival, and late toxicity rate between CIRT and XRT, for treating locoregional rectal cancer recurrence. Patients with rectal cancer who received reRT to the pelvis by CIRT or XRT from March 2005 to July 2019 were included. The CIRT treatment schedule was 70.4 Gy (relative biological effectiveness) in 16 fractions. For the XRT group, the median reRT dose was 50 Gy (range 25-62.5 Gy) with a median of 25 fractions (range 3-33). Thirty-five and 31 patients received CIRT and XRT, respectively. Tumour and treatment characteristics such as recurrence location and chemotherapy treatment differed between the two groups. CIRT showed better control of local recurrence (adjusted hazard ratio [HR] 0.17; p = 0.002), better overall survival (HR 0.30; p = 0.004), and lower severe late toxicity rate (HR 0.15; p = 0.015) than XRT. CIRT was effective for treating locoregional rectal cancer recurrence, with high rates of local control and survival, and a low late severe toxicity rate.


Assuntos
Radioterapia com Íons Pesados , Recidiva Local de Neoplasia/radioterapia , Reirradiação , Neoplasias Retais/radioterapia , Terapia por Raios X , Adulto , Idoso , Idoso de 80 Anos ou mais , Fracionamento da Dose de Radiação , Feminino , Radioterapia com Íons Pesados/efeitos adversos , Radioterapia com Íons Pesados/mortalidade , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Reirradiação/efeitos adversos , Reirradiação/mortalidade , Neoplasias Retais/mortalidade , Neoplasias Retais/patologia , Estudos Retrospectivos , Seul , Fatores de Tempo , Resultado do Tratamento , Terapia por Raios X/efeitos adversos , Terapia por Raios X/mortalidade
8.
N Engl J Med ; 386(6): 544-555, 2022 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-35139273

RESUMO

BACKGROUND: Patients with recurrent cervical cancer have a poor prognosis. Cemiplimab, the fully human programmed cell death 1 (PD-1)-blocking antibody approved to treat lung and skin cancers, has been shown to have preliminary clinical activity in this population. METHODS: In this phase 3 trial, we enrolled patients who had disease progression after first-line platinum-containing chemotherapy, regardless of their programmed cell death ligand 1 (PD-L1) status. Women were randomly assigned (1:1) to receive cemiplimab (350 mg every 3 weeks) or the investigator's choice of single-agent chemotherapy. The primary end point was overall survival. Progression-free survival and safety were also assessed. RESULTS: A total of 608 women were enrolled (304 in each group). In the overall trial population, median overall survival was longer in the cemiplimab group than in the chemotherapy group (12.0 months vs. 8.5 months; hazard ratio for death, 0.69; 95% confidence interval [CI], 0.56 to 0.84; two-sided P<0.001). The overall survival benefit was consistent in both histologic subgroups (squamous-cell carcinoma and adenocarcinoma [including adenosquamous carcinoma]). Progression-free survival was also longer in the cemiplimab group than in the chemotherapy group in the overall population (hazard ratio for disease progression or death, 0.75; 95% CI, 0.63 to 0.89; two-sided P<0.001). In the overall population, an objective response occurred in 16.4% (95% CI, 12.5 to 21.1) of the patients in the cemiplimab group, as compared with 6.3% (95% CI, 3.8 to 9.6) in the chemotherapy group. An objective response occurred in 18% (95% CI, 11 to 28) of the cemiplimab-treated patients with PD-L1 expression greater than or equal to 1% and in 11% (95% CI, 4 to 25) of those with PD-L1 expression of less than 1%. Overall, grade 3 or higher adverse events occurred in 45.0% of the patients who received cemiplimab and in 53.4% of those who received chemotherapy. CONCLUSIONS: Survival was significantly longer with cemiplimab than with single-agent chemotherapy among patients with recurrent cervical cancer after first-line platinum-containing chemotherapy. (Funded by Regeneron Pharmaceuticals and Sanofi; EMPOWER-Cervical 1/GOG-3016/ENGOT-cx9 ClinicalTrials.gov number, NCT03257267.).


Assuntos
Adenocarcinoma/tratamento farmacológico , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Carcinoma Adenoescamoso/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias do Colo do Útero/tratamento farmacológico , Adenocarcinoma/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Biomarcadores Tumorais/metabolismo , Carcinoma Adenoescamoso/mortalidade , Progressão da Doença , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Receptor de Morte Celular Programada 1/metabolismo , Qualidade de Vida , Análise de Sobrevida , Neoplasias do Colo do Útero/mortalidade
9.
Clin Cancer Res ; 28(11): 2278-2285, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35131903

RESUMO

PURPOSE: In patients with platinum-sensitive relapsed (PSR) ovarian cancer, olaparib maintenance monotherapy significantly improves progression-free survival (PFS) versus placebo. However, evidence in the Asian population is lacking. This is the first study to evaluate olaparib efficacy and tolerability exclusively in Asian patients with PSR ovarian cancer. PATIENTS AND METHODS: Considering the limited placebo effect and significant clinical benefit of olaparib in previous trials, and the rapid approval of olaparib in China, this phase III study was designed as an open-label, single-arm trial. Patients with high-grade epithelial PSR ovarian cancer were enrolled from country-wide clinical centers across China and Malaysia. Patients received oral olaparib (300 mg) twice daily until disease progression or unacceptable toxicity. Primary endpoint was median PFS (mPFS). Primary analysis of PFS using the Kaplan-Meier method was performed when data reached 60% maturity (clinicaltrials.gov NCT03534453). RESULTS: Between 2018 and 2020, 225 patients were enrolled, and 224 received olaparib; 35.7% had received ≥3 lines of chemotherapy, 35.3% had achieved complete response to their last line of platinum-based chemotherapy, and 41.1% had a platinum-free interval ≤12 months. At primary data cut-off (December 25, 2020), overall mPFS was 16.1 months; mPFS was 21.2 and 11.0 months in BRCA-mutated and wild-type BRCA subgroups, respectively. Adverse events (AE) occurred in 99.1% of patients (grade ≥3, 48.7%); 9.4% discontinued therapy due to treatment-related AEs. CONCLUSIONS: Olaparib maintenance therapy was highly effective and well tolerated in Asian patients with PSR ovarian cancer, regardless of BRCA status. This study highlights the promising efficacy of olaparib in this Asian population. See related commentary by Nicum and Blagden, p. 2201.


Assuntos
Neoplasias Ovarianas , Carcinoma Epitelial do Ovário/tratamento farmacológico , Feminino , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/mortalidade , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Ftalazinas/administração & dosagem , Ftalazinas/efeitos adversos , Piperazinas/administração & dosagem , Piperazinas/efeitos adversos
10.
PLoS One ; 17(2): e0263250, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35108323

RESUMO

BACKGROUND: The current study aimed to determine the association between timing and completion of adjuvant chemotherapy and outcomes in real-world patients with early-stage pancreatic cancer. METHODS: In this multi-center cohort study patients with early-stage pancreatic cancer who were diagnosed from 2007-2017 and underwent complete resection in the province of Saskatchewan were examined. Cox proportional multivariate analyses were performed for correlation with recurrence and survival. RESULTS: Of 168 patients, 71 eligible patients with median age of 69 years and M:F of 37:34 were identified. Median time to the start of adjuvant therapy from surgery was 73 days. Of all patients, 49 (69%) patients completed adjuvant chemotherapy and 22 (31%) required early treatment discontinuation. Median recurrence-free survival of patients who completed treatment was 22 months (95%CI:15.8-28.2) vs. 9 months (3.3-14.7) if treatment was discontinued early (P<0.001). Median overall survival of those who completed treatment was 33 (17.5-48.5) vs. 16 months (17.5-48.5) with early treatment discontinuation (P<0.001). In the multivariate analysis, treatment discontinuation was significantly correlated with recurrent disease, hazard ratio (HR), 2.57 (1.41-4.68), P = 0.002 and inferior survival, HR, 2.55 (1.39-4.68), P = 0.003. No correlation between treatment timing and survival was noted. CONCLUSIONS: Early discontinuation but not the timing of adjuvant chemotherapy correlates with inferior outcomes.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante/mortalidade , Recidiva Local de Neoplasia/mortalidade , Neoplasias Pancreáticas/mortalidade , Suspensão de Tratamento/estatística & dados numéricos , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
11.
BMC Cancer ; 22(1): 103, 2022 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-35078439

RESUMO

BACKGROUND: The study aimed to assess the impact of size differences of multiple liver metastases on liver recurrence-free survival (RFS) in patients undergoing hepatic resection for colorectal liver metastases (CRLMs). METHODS: Overall, 147 patients with CRLMs who underwent hepatic resection between January 2010 and December 2016 were retrospectively analysed. Tumour size ratio (TSR) was defined as the maximum diameter of the largest liver lesion over the maximum diameter of the smallest liver lesion. The univariate and multivariate analyses were performed to determine independent prognostic risk factors. The prognostic value of the TSR was further explored in each Tumour Burden Score (TBS) zone. Log-rank survival analyses were used to compare liver RFS in the new clinical score and the Fong clinical score. RESULTS: Based on the TSR, patients were classified into three groups: TSR < 2, 2 ≤ TSR < 4, and TSR ≥ 4. According to the multivariate analysis, TSR of 2-4 (hazard ratio [HR], 2.580; 95% confidence interval [CI] 1.543-4.312; P < 0.001) and TSR < 2 (HR, 4.435; 95% CI 2.499-7.872; P < 0.001) were associated with worse liver RFS. As TSR decreased, liver RFS worsened. TSR could further stratify patients in zones 1 and 2 into different risk groups according to the TBS criteria (zone 1: median liver RFS, 3.2 and 8.9 months for groups 1 and 2, respectively, P = 0.003; zone 2: median liver RFS, 3.5, 5.0, and 10.9 months for groups 1, 2, and 3, respectively, P < 0.05). The predictive ability of the new clinical score, which includes TSR, was superior to that of the Fong clinical score. CONCLUSIONS: TSR, as a prognostic tool, could accurately assess the effect of size differences across multiple liver metastases on liver RFS in patients undergoing hepatectomy for CRLMs. TRIAL REGISTRATION: Retrospectively registered.


Assuntos
Neoplasias Colorretais/patologia , Hepatectomia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/cirurgia , Carga Tumoral , Intervalo Livre de Doença , Feminino , Humanos , Fígado/patologia , Fígado/cirurgia , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Resultado do Tratamento
12.
BMC Cancer ; 22(1): 114, 2022 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-35086512

RESUMO

PURPOSE: The aim of this study was to investigate the epidemiological characteristics and associated risk factors of recurrent lower-grade glioma [LGG] (WHO grades II and III) according to the 2016 updated WHO classification paradigm and finally develop a model for predicting early mortality (succumb within a year after reoperation) in recurrent LGG patients. METHODS: Data were obtained from consecutive patients who underwent surgery for primary LGG and reoperation for tumor recurrence. The end point "early mortality" was defined as death within 1 year after the reoperation. Predictive factors, including basic clinical characteristics and laboratory data, were retrospectively collected. RESULTS: A final nomogram was generated for surgically treated recurrent LGG. Factors that increased the probability of early mortality included older age (P = 0.042), D-dimer> 0.187 (P = 0.007), RDW > 13.4 (P = 0.048), PLR > 100.749 (P = 0.014), NLR > 1.815 (P = 0.047), 1p19q intact (P = 0.019), IDH1-R132H Mutant (P = 0.048), Fib≤2.80 (P = 0.018), lack of Stupp concurrent chemoradiotherapy (P = 0.041), and an initial symptom of epilepsy (P = 0.047). The calibration curve between the prediction from this model and the actual observations showed good agreement. CONCLUSION: A nomogram that predicts individualized probabilities of early mortality for surgically treated recurrent LGG patients could be a practical clinical tool for counseling patients regarding treatment decisions and optimizing therapeutic approaches. Free online software implementing this nomogram is provided at https://warrenwrl.shinyapps.io/RecurrenceGliomaEarlyM/.


Assuntos
Neoplasias Encefálicas/mortalidade , Glioma/mortalidade , Recidiva Local de Neoplasia/mortalidade , Sistemas On-Line , Medição de Risco/métodos , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade Prematura , Nomogramas , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
13.
BMC Cancer ; 22(1): 11, 2022 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-34979982

RESUMO

BACKGROUND: The mixed-lineage leukemia (MLL) gene is located on chromosome 11q23. The MLL gene can be rearranged to generate partial tandem duplications (MLL-PTD), which occurs in about 5-10% of acute myeloid leukemia (AML) with a normal karyotype and in 5-6% of myelodysplastic syndrome (MDS) patients. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is currently one of the curative therapies available for AML and MDS with excess blasts (MDS-EB). However, how the prognosis of patients with high levels of MLL-PTD after allo-HSCT, and whether MLL-PTD could be used as a reliable indicator for minimal residual disease (MRD) monitoring in transplant patients remains unknown. Our study purposed to analyze the dynamic changes of MLL-PTD peri-transplantation and the best threshold for predicting relapse after transplantation. METHODS: We retrospectively collected the clinical data of 48 patients with MLL-PTD AML or MDS-EB who underwent allo-HSCT in Peking University People's Hospital. The MLL-PTD was examined by real-time quantitative polymerase chain reaction (RQ-PCR) at the diagnosis, before transplantation and the fixed time points after transplantation. Detectable MLL-PTD/ABL > 0.08% was defined as MLL-PTD positive in this study. RESULTS: The 48 patients included 33 AML patients and 15 MDS-EB patients. The median follow-up time was 26(0.7-56) months after HSCT. In AML patients, 7 patients (21.2%) died of treatment-related mortality (TRM), 6 patients (18.2%) underwent hematological relapse and died ultimately. Of the 15 patients with MDS-EB, 2 patients (13.3%) died of infection. The 3-year cumulative incidence of relapse (CIR), overall survival (OS), disease-free survival (DFS) and TRM were 13.7 ± 5.2, 67.8 ± 6.9, 68.1 ± 6.8 and 20.3% ± 6.1%, respectively. ROC curve showed that post-transplant MLL-PTD ≥ 1.0% was the optimal cut-off value for predicting hematological relapse after allo-HSCT. There was statistical difference between post-transplant MLL-PTD ≥ 1.0% and MLL-PTD < 1.0% groups (3-year CIR: 75% ± 15.3% vs. 0%, P < 0.001; 3-year OS: 25.0 ± 15.3% vs. 80.7% ± 6.6%, P < 0.001; 3-year DFS: 25.0 ± 15.3% vs. 80.7 ± 6.6%, P < 0.001; 3-year TRM: 0 vs. 19.3 ± 6.6%, P = 0.277). However, whether MLL-PTD ≥ 1% or MLL-PTD < 1% before transplantation has no significant difference on the prognosis. CONCLUSIONS: Our study indicated that MLL-PTD had a certain stability and could effectively reflect the change of tumor burden. The expression level of MLL-PTD after transplantation can serve as an effective indicator for predicting relapse.


Assuntos
Histona-Lisina N-Metiltransferase/genética , Leucemia Mieloide Aguda/genética , Síndromes Mielodisplásicas/genética , Proteína de Leucina Linfoide-Mieloide/genética , Recidiva Local de Neoplasia/genética , Proteínas de Fusão Oncogênica/genética , Intervalo Livre de Doença , Feminino , Seguimentos , Rearranjo Gênico/genética , Transplante de Células-Tronco Hematopoéticas , Humanos , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/cirurgia , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/mortalidade , Síndromes Mielodisplásicas/cirurgia , Recidiva Local de Neoplasia/mortalidade , Neoplasia Residual , Período Pós-Operatório , Valor Preditivo dos Testes , Prognóstico , Intervalo Livre de Progressão , Recidiva , Estudos Retrospectivos , Transplante Homólogo , Carga Tumoral/genética
14.
Future Oncol ; 18(8): 903-913, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35073733

RESUMO

Bempegaldesleukin (BEMPEG: NKTR-214) is an immunostimulatory IL-2 cytokine prodrug engineered to deliver a controlled, sustained and preferential IL-2 pathway signal. Nivolumab (NIVO), a PD-1 inhibitor, has been shown to prolong survival in patients with advanced melanoma and recurrence-free survival in the adjuvant setting. PIVOT-02 showed that BEMPEG plus NIVO was well-tolerated and demonstrated clinical activity as first-line therapy in metastatic melanoma. PIVOT-12 is a randomized, phase III, global, multicenter, open-label study comparing adjuvant therapy with BEMPEG plus NIVO versus NIVO alone in adult and adolescent patients with completely resected cutaneous stage III/IV melanoma at high risk of recurrence. The primary objective is to compare the efficacy, as measured by recurrence-free survival, of BEMPEG plus NIVO versus NIVO.


Following surgery, patients with advanced melanoma may require further treatment to reduce the likelihood of disease recurrence. Nivolumab (NIVO), a checkpoint inhibitor, reduces the risk of melanoma recurrence by enhancing the ability of the immune system to fight disease. Despite the availability of NIVO and other therapies, many patients with melanoma still experience disease recurrence after surgery. This article presents information on a clinical trial named PIVOT-12, which aims to assess the effectiveness of a new investigational drug called bempegaldesleukin that modifies the immune system and is given with NIVO to patients with stage III/IV melanoma following surgery. The main end point being measured is recurrence-free survival, which measures the time between a patient starting the study and the date of disease recurrence. Clinical Trial Registration: NCT04410445 (ClinicalTrials.gov).


Assuntos
Adjuvantes Imunológicos/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Interleucina-2/análogos & derivados , Interleucina-2/agonistas , Melanoma/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Nivolumabe/uso terapêutico , Polietilenoglicóis/uso terapêutico , Neoplasias Cutâneas/tratamento farmacológico , Adjuvantes Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/administração & dosagem , Intervalo Livre de Doença , Humanos , Infusões Intravenosas , Interleucina-2/administração & dosagem , Interleucina-2/uso terapêutico , Melanoma/mortalidade , Melanoma/secundário , Metástase Neoplásica , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Nivolumabe/administração & dosagem , Polietilenoglicóis/administração & dosagem , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Resultado do Tratamento
15.
Future Oncol ; 18(8): 1003-1022, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35094535

RESUMO

The present goal of therapy for early HR+/HER2- breast cancer (BC) is to optimize disease-free survival (DFS) and overall survival (OS) rates with the currently available therapies while avoiding any relevant long-term sequalae. Local therapies have evolved toward less aggressive techniques (i.e. breast-preserving surgery, sentinel lymph node biopsy and intraoperative radiotherapy), which significantly reduce the long-term sequalae observed with more radical treatments. Endocrine therapy (ET) is still the cornerstone of adjuvant treatment because it significantly reduces BC relapse and mortality. Adjuvant chemotherapy is today recommended only for a particular subset of patients with a high risk of recurrence with ET alone, identified through genomic assays, age and/or disease stage. Bisphosphonates reduce the risk of bone metastasis and produce a slight although statistically significant improvement in survival in postmenopausal women. The CDK 4/6 inhibitor abemaciclib has been recently approved by the US FDA for patients at high risk of relapse.


The goal of therapy for patients diagnosed with early HR+/HER2- breast cancer (BC) is to maximize survival rates while maintaining the quality of life and avoiding long-term sequalae. Local therapies have evolved toward less aggressive techniques, which significantly reduce the long-term sequalae observed with more radical approaches. Endocrine therapy (ET) remains as the cornerstone of adjuvant treatment because it significantly reduces BC relapse and mortality. Adjuvant chemotherapy is, however, recommended only for a particular subset of patients with a high-risk of recurrence with ET alone, identified through genomic assays together with clinical variables such as age and/or axillary involvement. Additionally, bisphosphonates reduce the risk of bone metastasis with a slight improvement in survival in postmenopausal women. The CDK 4/6 inhibitor abemaciclib has been recently approved by the US FDA for patients at high risk of relapse.


Assuntos
Neoplasias da Mama/terapia , Recidiva Local de Neoplasia/terapia , Receptor ErbB-2/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Árvores de Decisões , Intervalo Livre de Doença , Feminino , Humanos , Mastectomia , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia
16.
J Clin Oncol ; 40(7): 740-751, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-34995084

RESUMO

PURPOSE: Current tools in predicting survival outcomes for patients with colon cancer predominantly rely on clinical and pathologic characteristics, but increasing evidence suggests that diet and lifestyle habits are associated with patient outcomes and should be considered to enhance model accuracy. METHODS: Using an adjuvant chemotherapy trial for stage III colon cancer (CALGB 89803), we developed prediction models of disease-free survival (DFS) and overall survival by additionally incorporating self-reported nine diet and lifestyle factors. Both models were assessed by multivariable Cox proportional hazards regression and externally validated using another trial for stage III colon cancer (CALGB/SWOG 80702), and visual nomograms of prediction models were constructed accordingly. We also proposed three hypothetical scenarios for patients with (1) good-risk, (2) average-risk, and (3) poor-risk clinical and pathologic features, and estimated their predictive survival by considering clinical and pathologic features with or without adding self-reported diet and lifestyle factors. RESULTS: Among 1,024 patients (median age 60.0 years, 43.8% female), we observed 394 DFS events and 311 deaths after median follow-up of 7.3 years. Adding self-reported diet and lifestyle factors to clinical and pathologic characteristics meaningfully improved performance of prediction models (c-index from 0.64 [95% CI, 0.62 to 0.67] to 0.69 [95% CI, 0.67 to 0.72] for DFS, and from 0.67 [95% CI, 0.64 to 0.70] to 0.71 [95% CI, 0.69 to 0.75] for overall survival). External validation also indicated good performance of discrimination and calibration. Adding most self-reported favorable diet and lifestyle exposures to multivariate modeling improved 5-year DFS of all patients and by 6.3% for good-risk, 21.4% for average-risk, and 42.6% for poor-risk clinical and pathologic features. CONCLUSION: Diet and lifestyle factors further inform current recurrence and survival prediction models for patients with stage III colon cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante/mortalidade , Neoplasias do Colo/mortalidade , Dieta , Estilo de Vida , Modelos Estatísticos , Recidiva Local de Neoplasia/mortalidade , Nomogramas , Idoso , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Taxa de Sobrevida
17.
Urol Oncol ; 40(2): 57.e15-57.e23, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34325988

RESUMO

PURPOSE: To investigate the effect of time to prostate-specific antigen (PSA) nadir (TTN) after radiation therapy (RTx) for prostate cancer (PCa) on biochemical recurrence (BCR) and overall survival (OS) rates. PATIENTS AND METHODS: We analyzed 2,506 patients treated with RTx (external beam radiotherapy, brachytherapy or combinations) between years 2000 and 2021. Kaplan Meier and multivariable Cox regression models tested BCR-free survival and OS after stratification according to TTN (≤24 vs. 24.1-60 vs. >60 months). Similar analyses were performed after stratification according to absolute PSA values at nadir (<0.01 vs. 0.01-0.1 vs. 0.11-0.4 vs. >0.4 ng/ml). Finally, we repeated analyses after setting the time point of PSA nadir as the beginning of follow up in survival analyses. RESULTS: 10-year BCR-free survival rates were 55.5, 81.7 and 91.1% and OS rates were 71.5, 79.4 and 96.1% for TTN ≤24 months, 24.1 month-60 month and >60 months, respectively. Longer TTN was an independent predictor for BCR-free survival and OS (all P<0.001). However, after accounting for lead-time bias, in multivariable analyses, this association remained only significant for BCR-free survival (P≤0.03), but not for OS (P≥0.1). Finally, compared to a PSA nadir of <0.01 ng/ml, PSA nadir of 0.01-0.1 ng/ml, 0.11-0.4 ng/ml as well as >0.4 ng/ml were independent predictors for shorter BCR-free survival (P≤0.02), but not OS (P≥0.08). CONCLUSION: Shorter time to TTN and high PSA values at nadir are indicative of early treatment failure (BCR) and OS. However, after accounting for lead-time bias, this effect only remained valid for BCR.


Assuntos
Recidiva Local de Neoplasia/radioterapia , Antígeno Prostático Específico/metabolismo , Neoplasias da Próstata/radioterapia , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Neoplasias da Próstata/mortalidade , Taxa de Sobrevida
18.
Surg Today ; 52(2): 239-250, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34269851

RESUMO

PURPOSE: The significance of the duration of the recurrence-free survival after curative resection for colorectal cancer remains unclear. The purpose was to reveal the association between time to recurrence after surgery and the survival after recurrence. METHODS: Patients with stage II and III colorectal cancer who underwent curative resection between 2007 and 2015 were retrospectively reviewed (n = 645). Patients with recurrence after surgery (n = 133) were divided into 2 groups: early recurrence (within 13 months after surgery, n = 63) and late recurrence (more than 13 months after surgery, n = 70). The overall survival after recurrence and clinicopathological features were compared between early recurrence, late recurrence, and without recurrence groups. RESULTS: The overall survival after recurrence was significantly shorter in patients with early recurrence occurring at less than 13 months (hazard ratio: 1.70, p = 0.03). A high preoperative CA19-9 level (odds ratio [OR]: 2.38, p = 0.03), venous invasion (OR: 2.26, p = 0.03), and the absence of adjuvant chemotherapy (OR: 2.08, p = 0.04) were independently correlated with early recurrence. CONCLUSION: Early recurrence was associated with a poor prognosis after recurrence. Venous invasion correlated with early recurrence. Adjuvant chemotherapy may reduce the risk of early recurrence. These results indicate the importance of prudent surveillance and the aggressive application of adjuvant chemotherapy.


Assuntos
Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/cirurgia , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Recidiva Local de Neoplasia/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/prevenção & controle , Estadiamento de Neoplasias , Estudos Retrospectivos , Fatores de Tempo , Adulto Jovem
19.
Hematol Oncol ; 40(1): 82-91, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34664735

RESUMO

Prolonged isolated thrombocytopenia (PIT) is a common complication after umbilical cord blood transplantation (UCBT). However, data on PIT prediction and impacts on transplantation outcomes for UCBT patients are rare. We retrospectively analyzed 244 patients with hematological malignancies who received single-unit UCBT at the First Affiliated Hospital of USTC between August 2018 and December 2019. Among them, PIT occurred in 49 recipients, with a crude incidence of 20.1%. In the PIT patients, the 2-year cumulative incidence of transplant-related mortality (TRM) was significantly higher, and the probabilities of 2-year overall survival, leukemia-free survival and graft-versus-host disease (GVHD)-free relapse-free survival were significantly poorer (57.1% vs. 88.6%; 53.1% vs. 81.9%; 22.4% vs. 59.8%; p < 0.001), without remarkable increases in the cumulative incidence of relapse or chronic GVHD. Importantly, the multivariate analysis revealed that lower high-resolution HLA compatibility (≤6/10), lower infused CD34+ cell count (≤1.78 × 105 /kg), grade II-IV acute GVHD preplatelet engraftment, a lower pretransplantation platelet count (≤100 × 109 /L), and a longer neutrophil engraftment time (≥17 days) were independent risk factors for PIT after UCBT. These results demonstrate that PIT is common after UCBT, predicting inferior survival and the need for more monitoring during the early phase.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Doença Enxerto-Hospedeiro/mortalidade , Neoplasias Hematológicas/mortalidade , Recidiva Local de Neoplasia/mortalidade , Trombocitopenia/mortalidade , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Transplante de Células-Tronco de Sangue do Cordão Umbilical/mortalidade , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/patologia , Neoplasias Hematológicas/patologia , Neoplasias Hematológicas/terapia , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Trombocitopenia/etiologia , Trombocitopenia/patologia , Adulto Jovem
20.
Am Surg ; 88(3): 480-488, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34761683

RESUMO

BACKGROUND: Outcomes are thought to be worse in head and neck (H&N) melanoma patients. However, definitive evidence of inferior outcomes in H&N melanoma in the modern era is lacking. We sought to ascertain whether H&N melanomas carry a worse prognosis than melanomas of other sites. METHODS: All patients who underwent excision for primary melanoma by fellowship-trained surgical oncologists at a single institution from 2014 to 2020 were queried from the electronic medical record. Patients who had AJCC eighth edition stage I-III disease were included. RESULTS: Of 1127 patients, 28.7% had primary H&N melanoma. H&N patients were more likely to be male, older, and present with more advanced AJCC stage. Median follow-up was 20.0 months (IQR 26.4). On multivariable analyses controlling for other variables, H&N melanoma was associated with worse RFS. Notably, H&N melanoma was not associated with worse MSS, DMFS, or OS on univariate or multivariable analyses. Among patients who recurred, H&N patients were significantly more likely to recur locally compared to non-H&N patients. On subgroup analysis, scalp melanoma was also associated with worse RFS compared to patients with melanoma in locations other than the scalp. When patients with scalp melanoma were excluded from analysis, non-scalp H&N RFS was not significantly different from the non-H&N group on univariate or multivariable analyses. DISCUSSION: In this series from a high-volume tertiary referral center, the differences in rates and sites of recurrence between H&N and non-H&N melanoma do not impact melanoma-specific or overall survival, suggesting that H&N melanoma patients should be treated similarly with respect to regional and systemic therapies.


Assuntos
Neoplasias de Cabeça e Pescoço/mortalidade , Melanoma/mortalidade , Recidiva Local de Neoplasia/mortalidade , Neoplasias Cutâneas/mortalidade , Neoplasias Torácicas/mortalidade , Fatores Etários , Idoso , Análise de Variância , Feminino , Seguimentos , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Masculino , Melanoma/patologia , Melanoma/cirurgia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Couro Cabeludo , Fatores Sexuais , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgia , Análise de Sobrevida , Neoplasias Torácicas/patologia , Neoplasias Torácicas/cirurgia , Tronco , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...