RESUMO
BACKGROUND: Ubiquitin-conjugating enzyme E2W (UBE2W) is a protein-coding gene that has an important role in ubiquitination and may be vital in the repair of DNA damage. However, studies on the prognostic value of UBE2W and its correlation with tumor-infiltrating immune cells in multiple cancers have not been addressed. METHODS: We investigated UBE2W expression in the Oncomine database, the Tumor Immune Estimation Resource (TIMER), TNMplot database. Then, the clinical prognostic value of UBE2W was analyzed via online public databases. Meanwhile, we explored the correlation between UBE2W and DNA repair associate genes expression and DNA methyltransferase expression by TIMER and Gene Expression Profiling Interactive Analysis (GEPIA). By using the same method, the correlation between UBE2W and tumor-infiltrating immune cells was explored. Genomic Profiles of UBE2W in breast cancer (BRCA) were accessed in cBioPortal (v3.5.0). Functional proteins associated network was analyzed by STRING database (v11.0). RESULTS: UBE2W was abnormally expressed and significantly correlated with mismatch repair (MMR) gene mutation levels, DNA methyltransferase, and BRCA1/2 expression in breast cancer. High expression of UBE2W may promote the tumor immunosuppression and metastasis, induce endocrine therapy resistance and deteriorate outcomes of patients with breast cancer. These findings suggest that UBE2W could be a potential biomarker of prognosis and tumor-infiltrating immune cells. Besides, RBX1 may be a new E3 that was regulated by UBE2W. CONCLUSIONS: Ubiquitin E2 UBE2W is a potential prognostic biomarker and is correlated with immune infiltration in BRCA.
Assuntos
Neoplasias da Mama/imunologia , Neoplasias da Mama/metabolismo , Reparo de Erro de Pareamento de DNA/genética , Linfócitos do Interstício Tumoral , Enzimas de Conjugação de Ubiquitina/metabolismo , Neoplasias da Mama/mortalidade , Bases de Dados Factuais , Feminino , Expressão Gênica , Perfilação da Expressão Gênica , Genes BRCA1 , Genes BRCA2 , Humanos , Metiltransferases/metabolismo , Mutação , Neoplasias/metabolismo , Prognóstico , Microambiente Tumoral/imunologia , Enzimas de Conjugação de Ubiquitina/genética , UbiquitinaçãoRESUMO
BACKGROUND: The management of unresectable locally advanced colon cancer (LACC) remains controversial, as resection is not feasible. The goal of this study was to evaluate the treatment outcomes and toxicity of neoadjuvant chemoradiotherapy (NACRT) followed with surgery and adjuvant chemotherapy in patients with unresectable radically LACC. METHODS: We included patients who were diagnosed at our institution, 2010-2018. The neoadjuvant regimen consisted of radiotherapy and capecitabine/ 5-fluorouracil-based chemotherapy. RESULTS: One hundred patients were identified. The median follow-up time was 32 months. The R0 resection rate, adjusted nonmultivisceral resection rate and bladder preservation rate were 83.0, 43.0 and 83.3%, respectively. The pCR and clinical-downstaging rates were 18, and 81.0%%, respectively. The 3-year PFS and OS rates for all patients were 68.6 and 82.1%, respectively. Seventeen patients developed grade 3-4 myelosuppression, which was the most common adverse event observed after NACRT. Tumor perforation occurred in 3 patients during NACRT. The incidence of grade 3-4 surgery-related complications was 7.0%. Postoperative anastomotic leakage was observed in 3 patients. CONCLUSIONS: NACRT followed by surgery was feasible and safe for selected patients with LACC, and can be used as a conversion treatment to achieve satisfactory downstaging, long-term survival and quality of life, with acceptable toxicities.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Colo/terapia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Capecitabina/administração & dosagem , Capecitabina/efeitos adversos , Quimioterapia Adjuvante , Neoplasias do Colo/mortalidade , Neoplasias do Colo/patologia , Terapia Combinada , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Qualidade de Vida , Taxa de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: Anal squamous cell carcinoma (ASCC) is a rare malignant tumor with increasing incidence. The goal of our study was to analyze the treatment outcome and prognostic factors of ASCC in South China in the past half-century. METHODS: This study retrospectively included 59 patients with ASCC admitted from 1975 to 2018 in Sun Yat-sen University cancer center. The clinical records and follow-up information of all patients were collected. Survival analysis and univariate and multivariate regression analyses were performed using the "survival" and "survminer" packages of R software. RESULTS: In 59 patients, 5 patients had distant metastasis at diagnosis. Among 54 M0 stage patients, 33 patients received chemoradiotherapy (CRT), 19 patients received local surgery, and 2 patients refused curative treatment and received the best supportive treatment (BST). The most common grade 3-4 acute toxicities during treatment were myelosuppression and radiation dermatitis. The median follow-up time was 32 months. For the whole group, the 3-year and 5-year overall survival (OS) rates and disease-free survival (DFS) were 71.1% and 63.6%, and 73.4% and 69.0%, respectively. Multivariate regression analysis showed that the T3-4 stage was an independent prognostic risk factor for OS, progression-free survival (PFS), and DFS. And M1 was an independent prognostic risk factor for PFS and DFS. Patients in stage M0 mainly treated with CRT had better local control than those mainly treated with surgery (p = 0.027). For M0 patients, induction chemotherapy combined with CRT tends to prolong OS compared with CRT alone (p = 0.26). The 3-year colostomy-free survival for the whole group was 81.1%. CONCLUSIONS: CRT is recommended as the first choice for the treatment of M0 stage ASCC. Induction chemotherapy may bring better survival benefits for some patients. Patients with ASCC in China seem to have a better local control rate, which suggested different treatment strategies may be needed in China.
Assuntos
Neoplasias do Ânus/terapia , Carcinoma de Células Escamosas/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Ânus/mortalidade , Neoplasias do Ânus/patologia , Neoplasias do Ânus/cirurgia , Doenças da Medula Óssea/etiologia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Quimiorradioterapia/efeitos adversos , China/epidemiologia , Feminino , Seguimentos , Humanos , Quimioterapia de Indução/efeitos adversos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Radiodermite/etiologia , Estudos Retrospectivos , Análise de Sobrevida , Centros de Atenção Terciária , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Patients with locally advanced sigmoid colon cancer (LASCC) have limited treatment options and a dismal prognosis with poor quality of life. This retrospective study aimed to further evaluate the feasibility and efficacy of neoadjuvant chemoradiotherapy (NACRT) followed by surgery as treatment for select patients with unresectable LASCC. METHODS: We studied patients with unresectable LASCC who received NACRT between November 2010 and April 2019. The NACRT regimen consisted of intensity modulated radiotherapy (IMRT) of 50 Gy to the gross tumor and positive lymphoma node and 45 Gy to the clinical target volume. Capecitabinebased chemotherapy was administered every 2 (mFOLFOX6) or 3 weeks (CAPEOX). Surgery was scheduled 6-8 weeks after radiotherapy. RESULTS: Seventytwo patients were enrolled in this study. Patients had a regular follow-up (median, 41.1 months; range, 8.3-116.5 months). Seventyone patients completed NACRT, and sixty-five completed surgery. Resection with microscopically negative margins (R0 resection) was achieved in 64 patients (88.9%). Pathologic complete response was observed in 15 patients (23.1%), and multivisceral resection was necessary in 38 patients (58.3%). The cumulative probability of 3-year overall survival (OS) and progression-free survival (PFS) were 75.8 and 70.7%, respectively. CONCLUSIONS: For patients with unresectable LASCC, neoadjuvant chemoradiotherapy is feasible, surgery can be performed safely and may result in increased survival and organ preservation rates.
Assuntos
Quimiorradioterapia , Terapia Neoadjuvante , Neoplasias do Colo Sigmoide/terapia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Capecitabina/uso terapêutico , Colectomia , Feminino , Humanos , Irradiação Linfática , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Tratamentos com Preservação do Órgão , Intervalo Livre de Progressão , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada , Estudos Retrospectivos , Neoplasias do Colo Sigmoide/mortalidade , Neoplasias do Colo Sigmoide/patologia , Neoplasias do Colo Sigmoide/cirurgia , Taxa de SobrevidaRESUMO
BACKGROUND: The watch-and-wait strategy offers a non-invasive therapeutic alternative for rectal cancer patients who have achieved a clinical complete response (cCR) after chemoradiotherapy. This study aimed to investigate the long-term clinical outcomes of this strategy in comparation to surgical resection. METHODS: Stage II/III rectal adenocarcinoma patients who received neoadjuvant chemoradiotherapy and achieved a cCR were selected from the databases of three centers. cCR was evaluated by findings from digital rectal examination, colonoscopy, and radiographic images. Patients in whom the watch-and-wait strategy was adopted were matched with patients who underwent radical resection through 1:1 propensity score matching analyses. Survival was calculated and compared in the two groups using the Kaplan-Meier method with the log rank test. RESULTS: A total of 117 patients in whom the watch-and-wait strategy was adopted were matched with 354 patients who underwent radical resection. After matching, there were 94 patients in each group, and no significant differences in term of age, sex, T stage, N stage or tumor location were observed between the two groups. The median follow-up time was 38.2 months. Patients in whom the watch-and-wait strategy was adopted exhibited a higher rate of local recurrences (14.9% vs. 1.1%), but most (85.7%) were salvageable. Three-year non-regrowth local recurrence-free survival was comparable between the two groups (98% vs. 98%, P = 0.506), but the watch-and-wait group presented an obvious advantage in terms of sphincter preservation, especially in patients with a tumor located within 3 cm of the anal verge (89.7% vs. 41.2%, P < 0.001). Three-year distant metastasis-free survival (88% in the watch-and-wait group vs. 89% in the surgical group, P = 0.874), 3-year disease-specific survival (99% vs. 96%, P = 0.643) and overall survival (99% vs. 96%, P = 0.905) were also comparable between the two groups, although a higher rate (35.7%) of distant metastases was observed in patients who exhibited local regrowth in the watch-and-wait group. CONCLUSION: The watch-and-wait strategy was safe, with similar survival outcomes but a superior sphincter preservation rate as compared to surgery in rectal cancer patients achieving a cCR after neoadjuvant chemoradiotherapy, and could be offered as a promising conservative alternative to invasive radical surgery.
Assuntos
Adenocarcinoma/cirurgia , Quimiorradioterapia/métodos , Neoplasias Retais/cirurgia , Conduta Expectante/métodos , Adenocarcinoma/mortalidade , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Neoplasias Retais/mortalidade , Estudos RetrospectivosRESUMO
PURPOSE: To evaluate the outcomes of 45â¯Gy/15â¯fractions/once-daily and 45â¯Gy/30â¯fractions/twice-daily radiation schemes utilizing intensity-modulated radiation therapy (IMRT) in extensive stage small cell lung cancer (SCLC), and to build up a new radiobiological model for tumor control probability (TCP) considering multiple biological effects. METHODS: Fifty-eight consecutive patients diagnosed with extensive stage SCLC, treated with chemotherapy and chest irradiation, were retrospectively reviewed. Thirty-seven received hyperfractionated IMRT (Hyper-IMRT, 45â¯Gy/30â¯fractions/twice-daily) and 21 received hypofractionated IMRT (Hypo-IMRT, 45â¯Gy/15â¯fractions/once-daily). Local progression-free survival (LPFS) and overall survival (OS) were calculated and compared. An extended linear-quadratic (LQ) model, LQRG, incorporating cell repair, redistribution, reoxygenation, regrowth and Gompertzian tumor growth was created based on the clinical data. The TCP model was reformulated to predict LPFS. The classical LQ and TCP models were compared with the new models. Akaike information criterion (AIC) was used to assess the quality of the models. RESULTS: The 2-year LPFS (34.1% vs 27.9%, pâ¯=â¯0.44) and OS (76.9% vs 76.9%, pâ¯=â¯0.26) were similar between Hyper- and Hypo-IMRT patients. According to the LQRG model, the α/ß calculated was 9.2 (95% confidence interval: 8.7-9.9) Gy after optimization. The average absolute and relative fitting errors for LPFS were 9.1% and 18.7% for Hyper-IMRT, and 8.8% and 16.2% for Hypo-IMRT of the new TCP model, compared with 29.1% and 62.3% for Hyper-IMRT, and 30.7% and 65.3% for Hypo-IMRT of the classical model. CONCLUSIONS: Hypo- and Hyper-IMRT resulted in comparable local control in the chest irradiation of extensive stage SCLC. The LQRG model has better performance in predicting the TCP (or LPFS) of the two schemes.
Assuntos
Fracionamento da Dose de Radiação , Neoplasias Pulmonares/radioterapia , Radioterapia de Intensidade Modulada/métodos , Carcinoma de Pequenas Células do Pulmão/radioterapia , Humanos , Modelos Lineares , Neoplasias Pulmonares/mortalidade , Probabilidade , Hipofracionamento da Dose de Radiação , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/mortalidadeRESUMO
This retrospective study used a population-based national registry to determine the impact of local treatment modalities on survival in patients with metastatic esophageal cancer (EC). The Surveillance Epidemiology and End Results (SEER) database was used to identify patients with metastatic EC from 1988 to 2012. A total of 9,125 patients were identified. There were 426 patients underwent primary surgery, 4,786 patients were administered radiotherapy (RT) alone, 847 patients underwent surgery plus RT, and 3,066 patients without any local treatment. Multivariate analysis results indicated that year of diagnosis, age, race, histologic subtype, grade, and local treatment modalities were independent prognostic factors for overall survival (OS). The 5-year OS were 8.4%, 4.5%, 17.5%, and 3.4% in primary surgery, RT only, surgery plus RT, and no local treatment, respectively (P < 0.001). Subgroup analyses showed that the impact of RT was mainly reflected by preoperative radiotherapy, as patients received preoperative radiotherapy had significantly better OS than patients who underwent primary surgery alone and postoperative RT, the 5-year OS rates were 24.7%, 6.5%, and 7.8%, respectively, respectively (P < 0.001). Surgery plus RT, especially preoperative RT, may improve long-term survival of patients with metastatic EC.