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1.
Front Oncol ; 9: 1080, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31681609

RESUMO

Purpose: To analyze the prognostic factors and optimal response interval for stereotactic body radiotherapy (SBRT) in patients with lung oligometastases (OM) or oligoprogression (OP) from colorectal cancer (CRC). Method: Patients with lung OM or OP from CRC treated by SBRT at our hospital were included in this retrospective review. The local control (LC), response to SBRT in different evaluation interval and regional metastases (RM) was analyzed. The risk factor for LC and RM was calculated using the Kaplan-Meier method and compared using the Log-rank test. Multivariate analysis with a Cox proportional hazards model was used to test independent significance. Results: A total of 53 patients with 105 lung metastases lesions treated from 2012 to 2018 were involved in this retrospective study. The median biologically effective dose (BED) for these patients was 100 Gy (range: 75-131.2 Gy). Complete response (CR) increased from 27 (25.7%) to 46 (43.8%) lesions at 1.8 and 5.3 months following SBRT, and at the last follow-up, 52 (49.5%) lesions achieved CR. The median follow-up duration for all patients was 14 months (range: 5-63 months), and 1-year LC was 90.4%. During the follow-up, 10 lesions suffered local relapse after SBRT (9 of them occurred within 8 months after SBRT). The univariate analysis shows BED ≥ 100 Gy (P = 0.003) and gross tumor volume (GTV) < 1.6 cm3 (P = 0.011) were better predictors for 1-year LC. The patients with lung oligoprogression had higher 1-year RM when compared with patients with lung oligometastases (hazard ratio 2.78; 95% confidence interval [CI] 1.04-7.48, P = 0.042). Until the last follow up, 4 (7.5%) patients suffered grade 2 radiation pneumonitis, and no grade 3-4 toxicity was observed. Conclusions: SBRT provides favorable LC in CRC patients with lung OM or OP, and the GTV and BED can affect the LC. Radiology examinations nearly 5-6 months following SBRT appear to represent the final local effect of SBRT, and the patients with oligoprogression has higher RM.

2.
J Vis Exp ; (150)2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31498313

RESUMO

The presence of cancer stem cells (CSCs) has been associated with relapse or poor outcomes after radiotherapy. Studying radioresistant CSCs may provide clues to overcoming radioresistance. Voltage-gated calcium channel α2δ1 subunit isoform 5 has been reported as a marker for radioresistant CSCs in non-small cell lung cancer (NSCLC) cell lines. Using calcium channel α2δ1 subunit as an example of a CSC marker, methods to study the radiosensitivity of CSCs in NSCLC cell lines are presented. CSCs are sorted with putative markers by flow cytometry, and the self-renewal capacity of sorted cells is evaluated by sphere formation assay. Colony formation assay, which determines how many cells lose the ability to generate descendants forming the colony after a certain dose of radiation, is then performed to assess the radiosensitivity of sorted cells. This manuscript provides initial steps for studying the radiosensitivity of CSCs, which establishes the basis for further understanding of the underlying mechanisms.

3.
Radiat Oncol ; 14(1): 138, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31382984

RESUMO

BACKGROUND: The aim of this study was to explore the impact of including or excluding the ischiorectal fossa (IRF) within the clinical target volume during neoadjuvant chemoradiotherapy (NCRT) using intensity modulated radiotherapy, in locally advanced lower rectal cancer (LALRC). METHODS: We retrospectively analysed the data of 220 LALRC patients who received NCRT followed by abdominoperineal resection between January 2009 and January 2015. Six patients were excluded because of loss to follow-up, 90 patients received IRF irradiation (IRF group) while 124 patients did not (NIRF group). Survival, patterns of recurrence, and treatment toxicities were compared between the two groups. RESULTS: Overall, patient/treatment variables were well balanced except for surgical technique. Perineal wound complications in the IRF and NIRF groups, were 40.0 and 24.2%, respectively (p = 0.010); corresponding 3-year perineal recurrence rates, local recurrence free survival, overall survival, and distant relapse free survival were 4.4% vs. 2.4% (p = 0.670), 88.1% vs. 95.0% (p = 0.079), 82.6% vs. 88.4% (p = 0.087), and 61.9% vs. 81.0% (p = 0.026), respectively. Multivariate analyses demonstrated the following factors to be significantly related to perineal wound complications: irradiation of the IRF (odds ratio [OR] 2.892, p = 0.002), anaemia (OR 3.776, p = 0.010), operation duration > 180 min (OR 2.486, p = 0.007), and interval between radiotherapy and surgery > 8 weeks (OR 2.400, p = 0.010). CONCLUSIONS: Exclusion of the IRF from the clinical target volume during NCRT using intensity-modulated radiotherapy in LALRC could lower the incidence of perineal wound complications after abdominoperineal resection, without compromising oncological outcomes.

4.
Sci Total Environ ; 663: 662-672, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30731412

RESUMO

Since the completion of Three Gorges Dam in 2008, a large water-level fluctuation zone with anti-seasonal submergence has formed between the elevations of 145 m and 175 m in the Three Gorges Reservoir in China. In addition to hydrological regime, revegetation has also occurred in this water-level fluctuation zone. However, how the hydrological regime and revegetation regulate soil prokaryotic community remains unclear. Here, we investigated soil prokaryotic community structure, diversity and environmental parameters in different flooding zones from two soil layers (0-10 cm and 10-30 cm) at 6 locations along the water-level fluctuation zone from upstream to downstream. The soil prokaryotic diversity tended to decrease from upstream to downstream, and the alpha diversity was higher in the topsoil than in the deep soil at all sites. Flooding significantly enhanced the prokaryotic diversity compared to the control (i.e., permanent dry zone). The soil prokaryotic composition underwent deterministic processes in the upstream sites and stochastic processes in the downstream sites, with stronger stochastic processes in the topsoil than in the deep soil across all sites and elevations. As expected, the soil pH, moisture, NH4+-N, organic carbon and nitrogen were proven to be determinants of the prokaryotic community composition. Changes in plant traits (plant biomass, richness, and carbon content) after revegetation induced by submergence also played an important role in structuring the prokaryotic community. The prokaryotic community exhibited a shorter average path distance (GD) in the flooding zones compared to the control, with the shortest average degree (avgK) and the lowest levels of stability in the longer periodic inundation zones. Overall, our results suggest that soil properties and plant functional traits are critical controls of the prokaryotic community's ability to develop at regional scales and water submergence can likewise be an important factor for variations in the prokaryotic community composition in riparian zones.


Assuntos
Bactérias , Inundações , Microbiota , Microbiologia do Solo , Bactérias/classificação , China , Recursos Hídricos
5.
J Hematol Oncol ; 12(1): 16, 2019 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-30764882

RESUMO

The lungs are the second most common site of metastasis for colorectal cancer (CRC) after the liver. Rectal cancer is associated with a higher incidence of lung metastases compared to colon cancer. In China, the proportion of rectal cancer cases is around 50%, much higher than that in Western countries (nearly 30%). However, there is no available consensus or guideline focusing on CRC with lung metastases. We conducted an extensive discussion and reached a consensus of management for lung metastases in CRC based on current research reports and the experts' clinical experiences and knowledge. This consensus provided detailed approaches of diagnosis and differential diagnosis and provided general guidelines for multidisciplinary therapy (MDT) of lung metastases. We also focused on recommendations of MDT management of synchronous lung metastases and initial metachronous lung metastases. This consensus might improve clinical practice of CRC with lung metastases in China and will encourage oncologists to conduct more clinical trials to obtain high-level evidences about managing lung metastases.

6.
Zhonghua Wei Chang Wai Ke Za Zhi ; 21(11): 1240-1248, 2018 Nov 25.
Artigo em Chinês | MEDLINE | ID: mdl-30506534

RESUMO

OBJECTIVE: To investigate the long-term outcome of organ preservation with local excision or "watch and wait" strategy for mid-low rectal cancer patients evaluated as clinical complete remission (cCR) or near-cCR following neoadjuvant chemoradiotherapy (NCRT). METHODS: Clinical data of 62 mid-low rectal cancer patients evaluated as cCR/near-cCR after NCRT undergoing organ preservation surgery with local excision or receiving "watch and wait" strategy at Department of Gastrointestinal Surgery, Peking University Cancer Hospital and Institute from March 2011 to August 2017 were retrospectively analyzed. According to the approximate 1:2 pairing, 123 patients who underwent radical resection with complete pathological remission(ypCR) after neoadjuvant chemotherapy during the same period were selected for prognosis comparison. The primary endpoint of the study was 3-year non-regrowth disease-free survival (NR-DFS) and tumor specific survival (CSS). Survival analysis was performed using the Kaplan-Meier curve (Log-rank method). The secondary endpoint of the study was 3-year organ preservation and sphincter preservation. RESULTS: The retrospective study included 38 male and 24 female patients. The median age was 60 (31-79) years and the median distance from tumor to anal verge was 4(1-8) cm. The ratio of cCR and near-cCR was 79.0%(49/62) and 21.0%(13/62) respectively. Local regrowth rate was 24.2%(15/62). Of 15 with tumor regrowth, 9 patients received salvage radical rectal resection and no local recurrence was found during follow-up; 4 patients received salvage local excision among whom one patient had a local recurrence occurred patient; 2 patients refused further surgery. The overall metastasis rate was 8.1%(5/62), including resectable metastasis(4.8%,3/62) and unresectable metastasis (3.2%,2/62). The valid 3-year organ preservation rate and sphincter preservation rate were 85.5%(53/62) and 95.2%(59/62) respectively. The median follow-up was 36.2(8.6-89.0) months. The 3-year NR-DFS of patients with cCR and near-cCR was 88.6% and 83.1% respectively, which was not significantly different to that of patients with ypCR (94.7%, P=0.217). The 3-year CSS of patients with cCR and near-cCR was both 100%, which was not significantly different to that of patients with ypCR(93.4%, P=0.186). CONCLUSIONS: Mid-low rectal cancer patients with cCR or near-cCR after NCRT undergoing organ preservation with local excision or receiving "watch and wait" strategy have good long-term prognosis with low rates of local tumor regrowth and distant metastasis, which is similar to those with ypCR after radical surgery. This treatment mode may be used as an option for organ preservation in mid-low rectal cancer patients with good tumor remission after NCRT.


Assuntos
Quimiorradioterapia , Terapia Neoadjuvante , Neoplasias Retais , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Prognóstico , Neoplasias Retais/diagnóstico , Neoplasias Retais/terapia , Estudos Retrospectivos , Resultado do Tratamento , Conduta Expectante
7.
Cancer Manag Res ; 10: 5009-5018, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30464601

RESUMO

Purpose: Radiotherapy is a major treatment method for patients with non-small cell lung cancer (NSCLC). However, the presence of radioresistant cancer stem cells (CSCs) may be associated with disease relapse or a poor outcome after radiotherapy. Voltage-gated calcium channel α2δ1 subunit (encoded by the gene CACNA2D1) isoform 5 is a marker of CSCs in hepatocellular carcinoma. This study aimed to investigate the radiosensitivity of α2δ1-high cells in NSCLC cell lines. Materials and methods: NSCLC cell lines A549, H1975, H1299, and PC9 were used. CACNA2D1-knockdown and CACNA2D1-overexpressing cell lines were established by lentiviral infection. Colony formation assay was performed to determine radiosensitivity. Sphere formation assay in serum-free medium was performed to evaluate self-renewal capacity. Proteins associated with DNA damage repair were analyzed by immunofluorescence or Western blot. The monoclonal antibody of α2δ1 was applied alone or in combination with radiation either in vitro or in vivo to determine the anti-tumor effect of the antibody. Results: α2δ1-high cells showed greater sphere-forming efficiency than α2δ1-low cells and were relatively resistant to radiation. CACNA2D1 knockdown in A549 cells enhanced radiosensitivity, whereas CACNA2D1 overexpression in PC9 and H1975 cells reduced radiosensitivity, suggesting that α2δ1 imparted radioresistance to NSCLC cells. Analysis of proteins involved in DNA damage repair suggested that α2δ1 enhanced the efficiency of DNA damage repair. The monoclonal antibody of α2δ1 had a synergistic effect with that of radiation to block the self-renewal of α2δ1-high cells and enhanced the radiosensitivity of α2δ1-positive cells in colony formation assays. The combination of the α2δ1 antibody with radiation repressed A549 xenograft growth in vivo. Conclusion: α2δ1 enhances radioresistance in cancer stem-like cells in NSCLC. The α2δ1 monoclonal antibody sensitizes α2δ1-high cells to radiation, suggesting that the antibody may be used to improve the treatment outcome when combined with radiation in NSCLC.

8.
Clin Colorectal Cancer ; 17(2): e307-e313, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29525524

RESUMO

BACKGROUND: The purpose of this study was to retrospectively analyze the pattern and the management of recurrence of rectal cancer treated with 22-fraction intensity-modulated radiation therapy (IMRT). PATIENTS AND METHODS: This study included patients who underwent IMRT with gross tumor volume of 50.6 Gy in 22 fractions with concurrent capecitabine treatment over a period of 30 days, after which the patients underwent total mesorectal excision at Peking University Cancer Hospital (2007-2015). Study end points were local recurrence-free survival (LRFS), local disease-free survival (LDFS), disease-free survival (DFS), and cancer-specific survival (CSS). RESULTS: A total of 687 patients were included in our analysis. The median age was 57 years (range, 21-87 years), and 66.4% of the patients were male. The estimated 5-year LRFS and 5-year LDFS rates were 94.4% (95% confidence interval [CI], 92.1%-96.7%) and 96.1% (95% CI, 94.1%-98.1%), respectively. The estimated 3-year DFS and 5-year CSS rates were 77.5% (95% CI, 74.1%-80.9%) and 84.7% (95% CI, 80.9%-88.4%), respectively. Overall, 33.3% of patients (9 of 27) who developed local recurrence, 35.8% of patients (19 of 53) who developed lung metastasis, and 60% of patients (15 of 25) who developed liver metastasis received curative treatment after recurrence. The estimated 3-year survival after recurrence rates of patients who received curative versus palliative treatment were significantly different (87.8% vs. 15.3%, P = .000). CONCLUSION: Rectal cancer treated with the 22-fraction IMRT regimen provides good local control. More than one-fourth of patients who develop recurrence have the chance to receive curative treatment with the incorporation of a multidisciplinary team and achieves excellent survival after recurrence.


Assuntos
Adenocarcinoma/radioterapia , Metástase Neoplásica/patologia , Recidiva Local de Neoplasia/patologia , Neoplasias Retais/radioterapia , Adenocarcinoma/mortalidade , Adenocarcinoma/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Capecitabina/administração & dosagem , Quimiorradioterapia/métodos , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Metástase Neoplásica/terapia , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/terapia , Radioterapia de Intensidade Modulada/métodos , Neoplasias Retais/mortalidade , Neoplasias Retais/patologia , Estudos Retrospectivos , Adulto Jovem
9.
Redox Biol ; 14: 59-71, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-28869833

RESUMO

Despite the increasingly important role of Hippo-Yap in hepatocellular carcinoma (HCC) development and progression, little insight is available at the time regarding the specifics interaction of Yap and cancer cells migration. Here, we identified the mechanism by which tumor-intrinsic Yap deletion resulted in HCC migratory inhibition. Yap was greatly upregulated in HCC and its expression promoted the cells migration. Functional studies found that knockdown of Yap induced JNK phosphorylation which closely bound to the Bnip3 promoter and contributed to Bnip3 expression. Higher Bnip3 employed excessive mitophagy leading to mitochondrial dysfunction and ATP shortage. The insufficient ATP inactivated SERCA and consequently triggered intracellular calcium overload. As the consequence of calcium oscillation, Ca/calmodulin-dependent protein kinases II (CaMKII) was signaled and subsequently inhibited cofilin activity via phosphorylated modification. The phosphorylated cofilin failed to manipulate F-actin polymerization and lamellipodium formation, resulting into the impairment of lamellipodium-based migration. Collectively, our results identified Hippo-Yap as the tumor promoter in hepatocellular carcinoma that mediated via activation of cofilin/F-actin/lamellipodium axis by limiting JNK-Bnip3-SERCA-CaMKII pathways, with potential application to HCC therapy involving cancer metastasis.


Assuntos
Fatores de Despolimerização de Actina/metabolismo , Actinas/metabolismo , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Proteínas Nucleares/metabolismo , Transdução de Sinais , Fatores de Transcrição/metabolismo , Cálcio/metabolismo , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Carcinoma Hepatocelular/metabolismo , Proteínas de Ciclo Celular , Linhagem Celular Tumoral , Movimento Celular , Metabolismo Energético , Células Hep G2 , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Neoplasias Hepáticas/metabolismo , Proteínas de Membrana/metabolismo , Proteínas Nucleares/antagonistas & inibidores , Proteínas Nucleares/genética , Fosforilação , Proteínas Proto-Oncogênicas/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo , Fatores de Transcrição/antagonistas & inibidores , Fatores de Transcrição/genética , Regulação para Cima
10.
Oncotarget ; 8(59): 100165-100175, 2017 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-29245968

RESUMO

Purpose: Studies concerning tumor regression grade (TRG) after two-week course of radiotherapy (RT) are limited. We tried to assess associations of TRG and outcomes in patients with locally advanced rectal cancer (LARC) treated with preoperative two-week course of RT. Methods: 356 consecutive LARC patients were retrospectively assessed. Patients with complete/intermediate (TRG1-3) and poor (TRG4-5) regressions were compared for overall survival (OS), disease-free survival (DFS) and metastasis-free survival (MFS). Results: By univariate analysis, pretreatment and postoperative factors including TNM stages, ypT, ypN, surgical procedure, pathological grade, and TRG impacted survival outcomes. Complete/intermediate regressions (TRG1-3) had significantly improved survival outcomes compared with poor ones (TRG4-5) (5y-OS, 85.8% vs. 65.8%, P=0.001; 5y-DFS, 76.0% vs. 53.7%, P<0.001; 5y-MFS, 84.2% vs. 66.7%, P<0.001). Multivariate analysis showed that ypN (P<0.001) and pathological grade (P=0.018) were the most important independent prognostic factors for DFS. ypT (P=0.014) and ypN (P=0.001) were the independent prognostic factors for MFS. Meanwhile, ypT (P=0.009), ypN (P=0.001), surgical procedure (p=0.001), and TRG (p=0.019) were the independent prognostic factors for OS. Conclusions: Complete/intermediate TRG regressions had a more favorable prognosis than the poor group. When treated with preoperative two-week course of RT; ypT, ypN, surgical procedure, and TRG seem to affect OS.

11.
Zhonghua Wei Chang Wai Ke Za Zhi ; 20(4): 417-424, 2017 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-28440523

RESUMO

OBJECTIVE: To investigate the safety and efficacy of organ preservation surgery or "watch and wait" strategy for rectal cancer patients who are evaluated as clinical complete response(cCR) or near-cCR following neoadjuvant chemoradiotherapy (nCRT). METHOD: From March 2011 to June 2016, 35 patients with mid-low rectal cancers who were diagnosed as cCR or near-cCR following nCRT underwent organ preservation surgery with local excision or surveillance following "watch and wait" strategy in the Peking University Cancer Hospital. All the patients received re-evaluation and re-staging 6-12 weeks after the completion of nCRT, according to Habr-Gama and MSKCC criteria for the diagnosis of cCR or near-cCR. The near-cCR patients who received local excision and were pathologically diagnosed as T0Nx were also regarded as cCR. The end-points of this study included organ-preservation rate (OPR), sphincter-preservation rate (SPR), non-re-growth disease-free survival (NR-DFS), stoma-free survival, cancer-specific survival (CSS) and overall survival(OS). Kaplan-Meier curve was used to estimate the survival data at 3 years. RESULTS: A total of 35 cases were analyzed including 24 males (68.6%) and 11 females (31.4%). The median age was 60 (range 37-79) years and the median distance from tumor to anal edge was 4(2-8) cm. Thirty-three patients received 50.6 Gy/22f IMRT with capecitabine and two patients received 50 Gy/25f RT with capecitabine. The cCR and near-cCR rates were 74.3%(26/35) and 25.7%(9/35) respectively. Excision biopsy was performed in 4 near-cCR cases to confirm the diagnosis of cCR. The non-re-growth DFS rate was 14.3%(5/35) and the median time of tumor re-growth was 6.7 (4.7-37.4) months. In five patients with tumor re-growth, four were salvaged by radical rectal resections and one received local excision. The distant metastasis rate was 5.7%(2/35), one patient presented resectable liver metastasis and received radical resection, another patient presented multiple bone metastases and was still alive. The median follow-up time was 43.7(6.1-71.4) months. At three years, the organ-preservation rate was 88.6%(31/35), the sphincter-preservation rate was 97.1% (34/35). No local recurrence was observed in five patients who received salvage surgery. The non-re-growth DFS was 94.0%. Three patients died of non-rectal cancer related events. The cancer-specific survival was 100%, the overall survival was 92.7% and the stoma-free survival rate was 90.0%. CONCLUSIONS: Organ preservation surgery or "watch and wait" strategy for cCR or near-cCR patients is feasible and achieves good outcomes. This strategy can be an alternative to standard care, improve patient's quality of life and facilitate tailored treatment for mid-low rectal cancer following nCRT, however, it should be cautiously applied in near-cCR patients before local excision biopsy.


Assuntos
Canal Anal/cirurgia , Preservação de Órgãos , Neoplasias Retais/mortalidade , Neoplasias Retais/cirurgia , Resultado do Tratamento , Conduta Expectante/métodos , Adulto , Idoso , Biópsia , Quimiorradioterapia , Procedimentos Cirúrgicos do Sistema Digestório , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Recidiva Local de Neoplasia/prevenção & controle , Qualidade de Vida , Neoplasias Retais/terapia , Reoperação , Terapia de Salvação , Taxa de Sobrevida
12.
Am J Clin Oncol ; 40(3): 266-273, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25503430

RESUMO

OBJECTIVES: To evaluate local control and survival in locally advanced rectal adenocarcinoma patients who underwent a preoperative 2-week course of radiotherapy (RT) and to identify prognostic factors influencing the survival rate. METHODS: We analyzed 377 consecutively treated patients with locally advanced (T3/T4 or node positive) rectal adenocarcinoma. All patients underwent a preoperative 2-week course of RT (30 Gy in 10 fractions) followed by curative surgery. Regression model was used to examine prognostic factors for the disease-free survival (DFS) and overall survival (OS) rates. The Statistical Analysis System software package, version 9.3, was used for analysis. RESULTS: The median follow-up for all living patients was 63.8 months (range, 5.1 to 131.7). The 5-year DFS and OS rates were 64.5% (95% CI, 59.0-69.4) and 75.6% (95% CI, 70.5-80.0), respectively. The 5-year cumulative incidences of local recurrence and distant metastases were 5.4% (95% CI, 2.9-7.9) and 29.0% (95% CI, 23.9-30.1), respectively. The pathologic complete response rate was achieved in 17 patients (4.5%). The Multivariate Cox Regression model showed that factors affecting DFS were the surgical technique, pre-RT pathologic grade, ypT, ypN, and comorbidity; and factors improving OS were low anterior resection, low pre-RT grade, low ypT, and low ypN. CONCLUSIONS: Patients treated with preoperative RT with 30 Gy in 10 fractions had similar local control, 5-year DFS and OS to reported long course RT regimen. The surgical technique, pre-RT pathologic grade, ypT, and ypN seemed to affect the OS. Further study on combining a 2-week course of preoperative RT with concurrent chemotherapy would be warranted.


Assuntos
Adenocarcinoma/radioterapia , Adenocarcinoma/cirurgia , Recidiva Local de Neoplasia/diagnóstico , Neoplasias Retais/radioterapia , Neoplasias Retais/cirurgia , Adenocarcinoma/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Intervalo Livre de Doença , Fracionamento da Dose de Radiação , Feminino , Seguimentos , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Gradação de Tumores , Estadiamento de Neoplasias , Radioterapia Adjuvante , Neoplasias Retais/patologia , Fatores de Risco , Taxa de Sobrevida , Adulto Jovem
13.
Am J Transl Res ; 8(2): 1265-72, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27158413

RESUMO

BACKGROUND: Pelvic oligo-recurrence is common in rectal cancer patients, and some could not achieve radical resection. OBJECTIVE: The study was to analyze long-term outcomes and prognostic factors associated with survival in patients treated with intensity-modulated radiation therapy (IMRT). METHODS: Study participants were identified from rectal patients with pelvic oligo-recurrence without distant metastases, who were not suitable for surgery (n=135). Patients were recommended to receive concurrent chemotherapy in the course of IMRT (median dose 64.5 Gy, range: 45-70 Gy). Additionally, 24.4% (33/135) of patients received radical surgery after preoperative radiotherapy. Median time to pelvic failure was 25.4 months (range: 1-144 months). With a median follow-up period of 45.5 months (range: 3-104 months), 5-year overall survival (OS) and disease-free survival (DFS) were 55.6% and 45.5%, respectively. RESULTS: In univariate survival analysis, OS stratified by subsites indicated that 5-year OS for anastomotic recurrence (80.5%) was better than for anterior recurrence (57.7%) and other pelvic oligo-recurrences (44.5%) (P=0.005). Five-year DFS in the three groups was 60.3%, 49% and 36.6%, respectively (P=0.037). In multivariate survival analysis, pelvic oligo-recurrence and symptomatic recurrence patterns were independently associated with OS in recurrent rectal cancer after pelvic radiotherapy (RT). CONCLUSIONS: These results indicate that RT for rectal cancer patients with pelvic oligo-recurrence had favorable prognosis, especially for patients with anastomotic recurrence.

15.
Clin Colorectal Cancer ; 15(2): 152-7, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26508595

RESUMO

BACKGROUND: We previously reported the oncologic results for intermediate neoadjuvant radiotherapy (nRT) plus total mesorectal excision (TME) for locally advanced rectal cancer in a retrospective study. The objective of the present study was to further investigate the efficacy and long-term outcomes after this nRT regimen. PATIENTS AND METHODS: From 2002 to 2011, 382 patients with resectable locally advanced rectal cancer were treated at the Peking University Cancer Hospital with 30 Gy of intermediate nRT in 10 fractions (biologic equivalent dose, 36 Gy) plus TME. Surgery, RT, and pathologic examination were standardized. The primary endpoints were local recurrence-free survival (LRFS), cancer-specific survival (CSS), and overall survival (OS). RESULTS: The median patient age at the initial treatment was 58 years (range, 22-85 years). The median patient follow-up time was 5.5 years. The estimated 5-year LRFS, CSS, and OS were 93.6%, 79.0%, and 73.6%, respectively. Of the 382 patients, 4 (1%), 4 (1%), 4 (1%), and 11 (2.9%) patients died of postoperative complications, secondary malignancies, cardiovascular and/or neurologic events, or other causes, respectively. Seven patients (1.8%) developed late-onset ileus and died after conservative treatment in peripheral hospitals. CONCLUSION: The 10-fraction intermediate nRT regimen reported in the present study is efficient and safe. The long-term outcome is acceptable. This treatment schedule is useful as an alternative that provides efficiency, patient convenience, and low medical costs.


Assuntos
Adenocarcinoma/terapia , Procedimentos Cirúrgicos do Sistema Digestório , Terapia Neoadjuvante/métodos , Radioterapia Adjuvante/métodos , Neoplasias Retais/terapia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Neoplasias Retais/mortalidade , Neoplasias Retais/patologia , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Adulto Jovem
16.
Dis Colon Rectum ; 58(2): 186-92, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25585076

RESUMO

BACKGROUND: We previously conducted a prospective phase II clinical trial studying a unique 22-fraction neoadjuvant intensity-modulated radiotherapy with concurrent capecitabine treatment followed by total mesorectal excision for locally advanced rectal cancer. OBJECTIVE: The objective of this study was to retrospectively review the efficacy, toxicity, and surgical complications following intensity-modulated radiotherapy in patients who have rectal cancer. DESIGN: This was a retrospective study. SETTING: Data were gathered from a surgical database. PATIENTS: This study included patients who underwent intensity-modulated radiotherapy with gross tumor volume/clinical target volume of 50.6/41.8 Gy in 22 fractions with concurrent capecitabine treatment over a period of 30 days, after which the patients underwent surgery for rectal cancer in Peking University Cancer Hospital (2007-2013). MAIN OUTCOME MEASURES: The primary end points were acute toxicity, postoperative complications, and complete response rate. RESULTS: A total of 260 patients were included in our analysis. The median age was 55 years (range, 21-87 years), and 68.5% of the patients were male. The yield complete response rate was 18.5% (48/260). There were no grade 4 toxicity and perioperative mortality. The grade 3 toxicity rate was 5.8%, which included diarrhea (4.2%), neutropenia (1.2%), and radiation dermatitis (0.4%). The 30-day postoperative and severe complication (≥grade 3) rates were 23.1% and 2.7%. The anastomotic leakage rate was 3.3% (5/152). Perineal wound complications (29.2%, 28/96) represented the most common problem following abdominoperineal resection. The estimated 3-year local recurrence-free survival, cancer-specific survival, and disease-free survival rates were 94.2% (95% CI, 90.1%-98.3%), 92.2% (95% CI, 87.5%-97.0%), and 81.4% (95% CI, 75.4%-87.4%). LIMITATION: The retrospective nature and the single-arm design was the limitation of the study. CONCLUSION: The 22-fraction neoadjuvant intensity-modulated radiotherapy regimen used to treat rectal cancer in this study has a high efficacy rate and a low toxicity rate. Further studies are needed to better define the role of intensity-modulated radiotherapy for rectal cancer treatment in a neoadjuvant setting.


Assuntos
Adenocarcinoma/terapia , Antimetabólitos Antineoplásicos/uso terapêutico , Desoxicitidina/análogos & derivados , Fluoruracila/análogos & derivados , Terapia Neoadjuvante/métodos , Complicações Pós-Operatórias , Lesões por Radiação , Radioterapia de Intensidade Modulada/métodos , Neoplasias Retais/terapia , Reto/cirurgia , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Capecitabina , Quimiorradioterapia , Desoxicitidina/uso terapêutico , Intervalo Livre de Doença , Feminino , Fluoruracila/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Retais/patologia , Estudos Retrospectivos , Resultado do Tratamento , Carga Tumoral , Adulto Jovem
18.
Zhonghua Yi Xue Za Zhi ; 93(12): 924-6, 2013 Mar 26.
Artigo em Chinês | MEDLINE | ID: mdl-23863678

RESUMO

OBJECTIVE: To explore the clinical feasibility of accelerated partial breast irradiation (APBI) by intensity-modulated radiotherapy (IMRT). METHODS: Twenty-six patients with T1N0M0 breast cancer were enrolled into a prospective accelerated partial-breast IMRT protocol between January 2008 and January 2010. Inverse planning of IMRT was employed at a prescribed dose of 34 Gy/10 f/5 d. Acute radiation skin responses and clinical effects were observed. RESULTS: All of them completed radiation. During the radiation, Grade 1 of acute radiation skin reaction (mild hyperpigmentation) was seen in 8 patients and there was not > grade 2 of skin reaction. At Month 1 post-radiation, Grade 1 of acute radiation skin reaction (mild hyperpigmentation) was seen in all patients and there was not > grade 2 of skin reaction. At Month 3 post-radiation, all instances of acute radiation skin reactions recovered. The median follow-up period was 51 months (range: 35 - 59). The follow-up period of 23 patients were over 3 years. No local recurrences developed. The 3-year disease-free survival was 100%. Cosmesis was good or excellent in all cases at Year 2. CONCLUSION: External beam-partial breast irradiation delivered by IMRT is feasible for selected Chinese early-stage breast cancer patients after breast-conserving surgery. The cosmetic effect, local control rate and long-term survival rate are satisfactory. And acute radiation toxicity is quite low.


Assuntos
Neoplasias da Mama/radioterapia , Carcinoma Ductal de Mama/radioterapia , Radioterapia de Intensidade Modulada , Adulto , Idoso , Estudos de Viabilidade , Feminino , Humanos , Mastectomia Segmentar , Pessoa de Meia-Idade , Período Pós-Operatório , Estudos Prospectivos , Resultado do Tratamento
19.
Zhonghua Fu Chan Ke Za Zhi ; 48(10): 763-7, 2013 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-24406134

RESUMO

OBJECTIVE: To compare the clinical efficacy and safety of two chemotherapy regimens for concurrent chemoradiotherapy in patients with stage Ib2 to IVa squamous cell carcinoma of the uterine cervix. METHODS: Between November 2007 and November 2011, 146 patients with stage Ib2 to IVa squamous cell carcinoma of the uterine cervix who received concurrent chemoradiotherapy in Peking University Cancer Hospital were analyzed. All cases were divided into two groups according to the different chemotherapy regimens during radiation therapy, the group receiving radiotherapy concomitant with weekly cisplatin or nedaplatin alone (platinum alone group, n = 59), the group receiving radiotherapy concomitant with cisplatin plus fluorouracil or nedaplatin plus tegafur every 3 weeks (combined group, n = 87). There were no statistical difference in the clinical and pathological characteristics between the two groups. RESULTS: Patients were evaluated by pelvic examination and pelvic MRI after chemoradiotherapy for 3 months according to WHO criteria. The response rate were respectively 97% (57/59) and 93% (81/87) in platinum alone group and combined group, in which there was no significant difference (P = 0.249). The five-year overall survival and the five-year progression-free survival of platinum alone group and combined group were respectively 61.2% versus 69.5% (P > 0.05) and 43.3% versus 24.4% (P > 0.05). There were also no statistically significant differences between platinum alone group and combined group in the five-year local recurrence rate and five-year distant metastasis (11.8% versus 9.8%, 29.4% versus 38.7%; all P > 0.05). Acute gastrointestinal toxicities (nausea and vomiting) in combined group were exactly higher than that in the other group [78% (68/87) versus 51% (30/59), P < 0.01]. Moreover, anaemia was slightly more common in combined group [53% (46/87) versus 25% (15/59), P = 0.019]. However, the occurrence rate of the acute or late proctitis and cystitis did not reveal difference between two groups (P > 0.05). CONCLUSIONS: Both concurrent chemoradiotherapy regimens had similar efficacy on cervical cancer patients with stage Ib2 to IVa. But the toxicity was lower in patients with weekly platinum than those with platinum-based combined regimens during radiation therapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Cisplatino/administração & dosagem , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/radioterapia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma de Células Escamosas/patologia , Quimiorradioterapia , Cisplatino/efeitos adversos , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Neoplasias do Colo do Útero/patologia
20.
Chin J Cancer Res ; 25(6): 749-55, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24385704

RESUMO

OBJECTIVE: To assess the safety and clinical antiangiogenic effect of recombinant adenovirus-p53 (rAd-p53) combined with hyperthermia plus or not plus radiotherapy in advanced cancer. METHODS: Expression of Vascular epithelial growth factor (VEGF) after intratumoral injection of rAd-p53 was assayed by immunohistochemistry (IHC) imaging. Forty-four patients with advanced cancer were enrolled into this clinical study. The patients were intratumorally injected with rAd-p53 (Gendicine) at a dose of 1×10(12) vp once a week, with a total of 4-54 (mean 7.7) times. Total of 4-29 (mean 8.5) times of hyperthermia was given to the patients. Among the 44 patients, 30 patients were concurrently added with radiotherapy of a total dose 30-76 Gy/15-38 f/3-8 w (mean 58 Gy). RESULTS: Before and after intratumoral injection of rAd-p53, the VEGF IHC positive cell scores were 2.80 and 1.50, respectively (P=0.031). The treatment of rAd-p53 combined with hyperthermia plus or not plus radiotherapy in advanced cancer achieved CR rate of 13.60% (6/44), and PR rate of 29.6% (13/44), and thus the effective rate was 43.2%. In addition to 6 patients with CR, 19 patients (19/38, 50.0%) had low density area (LDA) of more than 50% area on CT image within tumor indicating tumor tissue necrosis. CONCLUSIONS: Our data indicate that rAd-p53 inhibits VEGF expression and angiogenesis, and promotes tumor necrosis and shrinkage induced by hyperthermia plus or not plus radiotherapy in advanced cancer.

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