Publications by authors named "Yuanhong Gao"

41 Publications

Oral Metronomic Maintenance Therapy Can Improve Survival in High-Risk Neuroblastoma Patients Not Treated with ASCT or Anti-GD2 Antibodies.

Cancers (Basel) 2021 Jul 13;13(14). Epub 2021 Jul 13.

State Key Laboratory of Oncology in South China, Guanghzou 510060, China.

Despite aggressive treatment, the prognosis of high-risk NB patients is still poor. This retrospective study investigated the benefits of metronomic maintenance treatment (MT) in high-risk NB patients without ASCT or GD2 antibody therapy. Patients aged ≤ 21 years with newly diagnosed high-risk NB were included. Patients with complete/very good partial remission (CR/VGPR/PR) to conventional treatment received, or not, oral metronomic MT for 1 year. Two hundred and seventeen high-risk NB patients were enrolled. One hundred and eighty-five (85%) had a CR/VGPR/PR to conventional treatment, of the patients with stage 4, 106 receiving and 61 not receiving oral metronomic MT, and the 3-year event-free survival (EFS) rate was 42.5 ± 5.1% and 29.6 ± 6%, respectively ( = 0.017), and overall survival (OS) rate was 71.1 ± 4.7% and 59.4 ± 6.4%, respectively ( = 0.022). A total of 117 high-risk patients with oral metronomic MT had EFS rate of 42.7 ± 4.8%. The toxicity of MT was mild. For high-risk NB patients without ASCT or anti-GD2 antibody therapy, stage 4, MYCN amplication and patients with stage 4 not receiving oral metronomic MT after CR/VGPR/PR were independent adverse prognostic factors. Oral metronomic MT can improve survival in high-risk NB patients in CR/VGPR/PR without ASCT or anti-GD2 antibodies therapy.
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http://dx.doi.org/10.3390/cancers13143494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8303783PMC
July 2021

ASO Visual Abstract: A Nomogram Based on a Collagen Feature Support Vector Machine for Predicting the Treatment Response to Neoadjuvant Chemoradiotherapy in Rectal Cancer Patients.

Ann Surg Oncol 2021 Jul 18. Epub 2021 Jul 18.

Department of General Surgery, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, The First School of Clinical Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.

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http://dx.doi.org/10.1245/s10434-021-10238-0DOI Listing
July 2021

Ultrathin and Ultrasensitive Direct X-ray Detector Based on Heterojunction Phototransistors.

Adv Mater 2021 Jul 5:e2101717. Epub 2021 Jul 5.

Materials Interfaces Center, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, P. R. China.

Most contemporary X-ray detectors adopt device structures with non/low-gain energy conversion, such that a fairly thick X-ray photoconductor or scintillator is required to generate sufficient X-ray-induced charges, and thus numerous merits for thin devices, such as mechanical flexibility and high spatial resolution, have to be compromised. This dilemma is overcome by adopting a new high-gain device concept of a heterojunction X-ray phototransistor. In contrast to conventional detectors, X-ray phototransistors allow both electrical gating and photodoping for effective carrier-density modulation, leading to high photoconductive gain and low noise. As a result, ultrahigh sensitivities of over 10  μC Gy  cm with low detection limit are achieved by just using an ≈50 nm thin photoconductor. The employment of ultrathin photoconductors also endows the detectors with superior flexibility and high imaging resolution. This concept offers great promise in realizing well-balanced detection performance, mechanical flexibility, integration, and cost for next-generation X-ray detectors.
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http://dx.doi.org/10.1002/adma.202101717DOI Listing
July 2021

Single-cell analyses reveal suppressive tumor microenvironment of human colorectal cancer.

Clin Transl Med 2021 Jun;11(6):e422

Affiliated Cancer Hospital and Institute of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, Guangzhou, China.

Profiling heterologous cell types within tumors is essential to decipher tumor microenvironment that shapes tumor progress and determines the outcome of therapeutic response. Here, we comprehensively characterized transcriptomes of 34,037 single cells obtained from 12 treatment-naïve patients with colorectal cancer. Our comprehensive evaluation revealed attenuated B-cell antigen presentation, distinct regulatory T-cell clusters with different origin and novel polyfunctional tumor associated macrophages associated with CRC. Moreover, we identified expanded XCL1 T-cell clusters associated with tumor mutational burden high status. We further explored the underlying molecular mechanisms by profiling epigenetic landscape and inferring transcription factor motifs using single-cell ATAC-seq. Our dataset and analysis approaches herein provide a rich resource for further study of the impact of immune cells and translational research for human colorectal cancer.
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http://dx.doi.org/10.1002/ctm2.422DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8181206PMC
June 2021

Nomogram to Predict Distant Metastasis Probability for Pathological Complete Response Rectal Cancer Patients After Neoadjuvant Chemoradiotherapy.

Cancer Manag Res 2021 15;13:4751-4761. Epub 2021 Jun 15.

Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China.

Purpose: This study aimed to predict the risks of distant metastasis (DM) of locally advanced rectal cancer (LARC) patients with pathological complete response (pCR) after neoadjuvant chemoradiotherapy (NACRT) and total mesorectal excision (TME), and to find the association between adjuvant chemotherapy (ACT) and their survival outcomes.

Methods And Materials: A total of 242 patients with LARC achieving pCR after NACRT were enrolled in this retrospective study. We developed a nomogram model using logistic regression analyses for predicting risk of DM. The model performance was evaluated by the concordance index and calibration curve. Survival was determined using Kaplan-Meier survival curve.

Results: Age, pre-operative CEA, pre-treatment CEA and distance of tumor to anal verge were identified as significantly associated variables that could be enrolled in the model to predict the risk of DM for pCR patients. The nomogram we created had a bootstrapped-concordance index of 0.731 (95% CI = 0.627 to 0.834) and was well calibrated. The high risk group was more likely to develop DM than low risk group (total score) (95% CI = 1.439 to 6.493, = 0.0036). The 1-year, 3-year, and 5-year distant metastasis-free survival (DMFS) for the low and high risk groups (total score ≤ 90 vs > 90) was 97.8%, 94.2%, 94.2% and 91.3%, 83.4%, 81.8%, respectively ( = 0.0036). DM occurred within 1 and 2 years after TME surgery was 33.3% and 55.6% for the low risk group, and 47.3% and 84.2% for the high risk group. The value of ACT was assessed among the whole cohort, patients with cT, with cN or with either DM risk group, but no significant difference was observed concerning DMFS whether ACT was given or not (all > 0.05). Active treatment after DM was more beneficial than palliative treatment ( < 0.001).

Conclusion: The nomogram model, including age, pre-operative CEA, pre-treatment CEA and distance to anal verge, predicted the probability of DM among LARC patients achieving pCR after NACRT. The effects of ACT were not seen in different subgroups, while closer clinical follow-up may have greater contribution to pCR patients in the first 2 years, especially for patients with relatively higher risk to develop DM. It is suggested that timely active treatment can bring survival benefit for pCR patients developing DM after NACRT.
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http://dx.doi.org/10.2147/CMAR.S313113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8214524PMC
June 2021

A Nomogram Based on a Collagen Feature Support Vector Machine for Predicting the Treatment Response to Neoadjuvant Chemoradiotherapy in Rectal Cancer Patients.

Ann Surg Oncol 2021 Jun 19. Epub 2021 Jun 19.

Department of General Surgery, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, People's Republic of China.

Background: The relationship between collagen features (CFs) in the tumor microenvironment and the treatment response to neoadjuvant chemoradiotherapy (nCRT) is still unknown. This study aimed to develop and validate a perdition model based on the CFs and clinicopathological characteristics to predict the treatment response to nCRT among locally advanced rectal cancer (LARC) patients.

Methods: In this multicenter, retrospective analysis, 428 patients were included and randomly divided into a training cohort (299 patients) and validation cohort (129 patients) [7:3 ratio]. A total of 11 CFs were extracted from a multiphoton image of pretreatment biopsy, and a support vector machine (SVM) was then used to construct a CFs-SVM classifier. A prediction model was developed and presented with a nomogram using multivariable analysis. Further validation of the nomogram was performed in the validation cohort.

Results: The CFs-SVM classifier, which integrated collagen area, straightness, and crosslink density, was significantly associated with treatment response. Predictors contained in the nomogram included the CFs-SVM classifier and clinicopathological characteristics by multivariable analysis. The CFs nomogram demonstrated good discrimination, with area under the receiver operating characteristic curves (AUROCs) of 0.834 in the training cohort and 0.854 in the validation cohort. Decision curve analysis indicated that the CFs nomogram was clinically useful. Moreover, compared with the traditional clinicopathological model, the CFs nomogram showed more powerful discrimination in determining the response to nCRT.

Conclusions: The CFs-SVM classifier based on CFs in the tumor microenvironment is associated with treatment response, and the CFs nomogram integrating the CFs-SVM classifier and clinicopathological characteristics is useful for individualized prediction of the treatment response to nCRT among LARC patients.
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http://dx.doi.org/10.1245/s10434-021-10218-4DOI Listing
June 2021

Associations between clinical characteristics and tumor response to neoadjuvant chemoradiotherapy in rectal cancer.

Cancer Med 2021 Jul 15;10(14):4832-4843. Epub 2021 Jun 15.

Department of Radiation Oncology, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.

Following standard neoadjuvant chemoradiotherapy and total mesorectal excision, some patients with locally advanced rectal cancer achieve good response (pathological T0-2N0), while others show nonresponse (pathological T3-4N0 or node-positive). To date, the clinicopathological predictors of good response and the necessity of adjuvant chemotherapy treatment (ACT) in good responders remain unclear. In this retrospective study, clinicopathological characteristics were surveyed to investigate the correlation with good response; furthermore, a propensity score matching (PSM) model was designed to balance the confounding factors between good responders treated with ACT or observation. A total of 2255 patients were enrolled, including 1069 good responders and 1186 nonresponders. The results of the survival analysis showed a good response predicted a better 3-year prognosis (p < 0.001). The logistic regression analysis showed less advanced T and N stages (T3 vs. T4; N0 vs. N1-2), more neoadjuvant chemotherapy (nCT) cycles (≥4 vs. 1-3), and delayed surgery (≥8 weeks vs. <8 weeks) were independent predictors of a good response (p < 0.05). Especially, patients treated with both more nCT cycles and a delay in surgery included the greatest number of good responders (p < 0.001). For good responders, after PSM (1:3), 235 observation cases were matched to 705 ACT cases. As compared with observation, ACT had no greater impact on prognosis analysis (p > 0.05). In conclusion, more cycles of nCT and a delay in surgery predicted a better response, and the delivery of ACT might be omitted in good responders.
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http://dx.doi.org/10.1002/cam4.4051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290248PMC
July 2021

ASO Author Reflections: Prediction of Treatment Response to Neoadjuvant Chemoradiotherapy Based on a Collagen Features Model in Rectal Cancer Patients.

Ann Surg Oncol 2021 May 28. Epub 2021 May 28.

Department of General Surgery, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, Guangdong, China.

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http://dx.doi.org/10.1245/s10434-021-10229-1DOI Listing
May 2021

Total Neoadjuvant Therapy (TNT) versus Standard Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer: A Systematic Review and Meta-Analysis.

Oncologist 2021 May 13. Epub 2021 May 13.

Departments of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.

Background: Total neoadjuvant therapy (TNT) is a novel approach for locally advanced rectal cancer (LARC), which attempts to deliver both systemic chemotherapy and neoadjuvant chemoradiotherapy prior to surgery. However, its efficacy and safety remain controversial in randomized controlled trials (RCTs). We conducted this meta-analysis to assess such concerns.

Materials And Methods: Head-to-head phase II/III RCTs were searched in Embase, PubMed, Web of Science, and the Cochrane Library, as well as other sources. The primary endpoint was pathologic complete response (pCR). Secondary endpoints were disease-free survival (DFS), overall survival (OS), local recurrence-free survival, distant metastasis-free survival, and the R0 resection rate.

Results: Eight phase II/III RCTs involving 2,196 patients with LARC were assessed. The primary analysis demonstrated a statistically significant improvement in the pCR rate for TNT treatment (odds ratio, 1.77; 95% confidence interval [CI], 1.28-2.45; p = .0005). TNT treatment also showed improvements in DFS and OS outcomes compared with standard chemoradiotherapy (hazard ratio [HR], 0.83; 95% CI, 0.72-0.96; p = .03 and HR, 0.88; 95% CI, 0.74-1.05; p = .15). In addition, TNT treatment showed significant efficacy in reducing the risk of distant metastasis (HR, 0.81; 95% CI, 0.68-0.95; p = .012).

Conclusion: The overall pCR rate may be improved with TNT compared with standard treatment. The TNT strategy may also improve DFS and OS and reduce the risk of distant metastasis.

Implications For Practice: Locally advanced rectal cancer (LARC) is a relatively common disease, with a poor prognosis because of its high metastatic potential. The role of total neoadjuvant therapy (TNT) has always been controversial. This meta-analysis found that TNT in LARC is associated with a significant improvement in overall pathologic complete response rate, disease-free survival, overall survival, and distant metastasis-free survival compared with standard treatment. TNT is a promising strategy for LARC, especially for patients who have little desire for surgery.
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http://dx.doi.org/10.1002/onco.13824DOI Listing
May 2021

DGKA Mediates Resistance to PD-1 Blockade.

Cancer Immunol Res 2021 04 19;9(4):371-385. Epub 2021 Feb 19.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.

Immunologic checkpoint blockade has been proven effective in a variety of malignancies. However, high rates of resistance have substantially hindered its clinical use. Understanding the underlying mechanisms may lead to new strategies for improving therapeutic efficacy. Although a number of signaling pathways have been shown to be associated with tumor cell-mediated resistance to immunotherapy, T cell-intrinsic resistant mechanisms remain elusive. Here, we demonstrated that diacylglycerol kinase alpha (Dgka) mediated T-cell dysfunction during anti-PD-1 therapy by exacerbating the exhaustion of reinvigorated tumor-specific T cells. Pharmacologic ablation of Dgka postponed T-cell exhaustion and delayed development of resistance to PD-1 blockade. Dgka inhibition also enhanced the efficacy of anti-PD-1 therapy. We further found that the expression of DGKA in cancer cells promoted tumor growth via the AKT signaling pathway, suggesting that DGKA might be a target in tumor cells as well. Together, these findings unveiled a molecular pathway mediating resistance to PD-1 blockade and provide a potential therapeutic strategy with combination immunotherapy.
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http://dx.doi.org/10.1158/2326-6066.CIR-20-0216DOI Listing
April 2021

Colorectal cancer under 20 years old: a retrospective analysis from three tertiary hospitals.

J Cancer Res Clin Oncol 2021 Apr 23;147(4):1145-1155. Epub 2020 Sep 23.

Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, China.

Purpose: Colorectal cancer (CRC) rarely occurs in children and adolescents. This study aimed to perform a retrospective analysis and disclose more detailed information about CRC in patients under 20 years old.

Methods: Medical records of CRCs in patients under 20 years old referred to three tertiary hospitals in China from September 2000 to July 2019 were retrospectively reviewed. Clinicopathological characteristics, treatment processes and laboratory findings were summarized and treatment outcomes and prognostic factors were analyzed.

Results: A total of 33,394 CRC medical records were analyzed, and we identified seventy (0.21%) CRCs in patients under 20. The most common primary tumor location was the left hemicolon (35.7%). The prominent pathological types were mucinous adenocarcinoma (22.9%) and signet ring cell carcinoma (22.9%). Nearly half (47.1%) of the patients presented with distant metastasis at diagnosis. The fractions of patients with deficient mismatch repair (dMMR) protein expression and microsatellite instability-high (MSI-H) were 23.8% (5/21) and 71.4% (5/7), respectively. Forty-four patients underwent radical surgery. Fifty-five patients received chemotherapy and six patients received radiotherapy. One dMMR/MSI-H rectal cancer patient received immunotherapy and achieved a clinically complete response. The median overall survival (OS) time was 80 months. The 3-year and 5-year OS rates were 61.8% and 57.2%, respectively. An absence of distant metastasis was a favorable factor for OS. For stage II/III CRCs, classic adenocarcinoma and radical surgery were favorable factors for OS. For stage IV CRCs, primary location at the colon was a favorable factor for OS.

Conclusion: Child and adolescent CRC patients are likely to have distant metastasis, undifferentiated, left hemicolon location, and a dMMR/MSI-H phenotype at diagnosis. Additional efforts are needed to improve their survival outcomes.
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http://dx.doi.org/10.1007/s00432-020-03397-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7954766PMC
April 2021

The prognosis of prechemotherapy blastemal predominant histology subtype in Wilms tumor: A retrospective study in China.

Pediatr Blood Cancer 2020 11 19;67(11):e28567. Epub 2020 Aug 19.

Department of Pediatric Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, P. R. China.

Purpose: This study aimed to retrospectively analyze survival outcomes for Chinese patients with prechemotherapy blastemal predominant histology type Wilms tumors (WTs).

Methods: We collected and analyzed clinical data concerning patients aged <15 years with favorable histology (FH) WTs treated at the Sun Yat-Sen University Cancer Center from December 2005 to May 2016, based on the Children's Oncology Group protocol. Pathological specimens were collected through biopsy or surgical resection before initiation of chemotherapy. We analyzed survival outcomes involving different prechemotherapy histology subtypes.

Results: We enrolled 97 patients with FH WTs (median follow-up, 71.5 months; range, 22.2-170.7). The total recurrence rate was 17.5%, and the subtype recurrence rates were as follows: blastemal predominant (45.5%), mixed (7.5%), epithelial (14.3%), and mesenchymal (9.5%) (P = .010). Five-year event-free survival (EFS) and overall survival (OS) rates were 84.9% and 81.4%, respectively. Respective 5-year EFS and OS rates for subtypes were as follows: blastemal predominant (54.5% and 68.2%), mixed (90.0% and 88.9%), epithelial (85.7% and 85.1%), and mesenchymal (90.5% and 94.7%). Multivariate survival analyses showed that the blastemal predominant subtype was an independent prognostic factor of EFS (P = .001) and OS (P = .017).

Conclusions: Our findings showed that prechemotherapy blastemal predominant WTs had higher recurrence and lower EFS and OS rates. Our findings suggested that, albeit with some deficiencies, blastemal predominant histology WT-diagnosed prechemotherapy may have prognostic relevance. Further research into other potential confounding variables are required to determine whether such patients warrant altered risk-stratified therapy.
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http://dx.doi.org/10.1002/pbc.28567DOI Listing
November 2020

Clinical characteristics and prognosis of anal squamous cell carcinoma: a retrospective audit of 144 patients from 11 cancer hospitals in southern China.

BMC Cancer 2020 Jul 21;20(1):679. Epub 2020 Jul 21.

School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen, 518107, China.

Background: The incidence of anal squamous cell carcinoma (SCC) has been steadily growing globally in the past decade. Clinical data on anal SCC from China are rare. We conducted this study to describe the clinical and epidemiological characteristics of anal SCC in China and explore prognostic factors of outcomes among patients with anal SCC.

Methods: We audited demographic characteristics, relevant symptoms, risk factors, treatment modalities and outcomes for patients diagnosed with anal SCC at 11 medical institutions in China between January 2007 and July 2018.

Results: A total of 144 patients (109 females) were diagnosed with SCC during this period. Median age at initial diagnosis was 52.0 (interquartile range: 46.0-61.8) years. The most common symptoms were bleeding (n = 93, 64.6%), noticing a lump (n = 49, 34.0%), and pain (n = 47, 32.6%). The proportion of patients at the American Joint Committee on Cancer (AJCC) stages I-IV were 10 (6.9%), 22 (15.3%), 61 (42.4%) and 8 (5.6%), respectively, and AJCC stages in 43 (29.9%) patients were unknown. Thirty-six patients (25.0%) underwent abdominoperineal resection initially. Univariable analysis showed that T stage predicted recurrence-free survival (RFS) (Hazard ratio [HR] = 3.03, 95% Confidence interval [CI]: 1.10-8.37, p = 0.032), and age group (HR = 2.90, 95% CI: 1.12-7.49, p = 0.028), AJCC stage (HR = 4.56, 95% CI: 1.02-20.35, p = 0.046), and N stage (HR = 3.05, 95% CI: 1.07-8.74, p = 0.038) predicted overall survival (OS).

Conclusions: T stage was identified as prognostic factor of RFS, and age, AJCC stage, and N stage were identified as prognostic factors of OS. Improving symptom awareness and earlier presentation among patients potentially at risk for anal SCC should be encouraged. Familiarity with the standard treatment among health care providers in China should be further improved.
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http://dx.doi.org/10.1186/s12885-020-07170-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7372759PMC
July 2020

Targeting SGK1 enhances the efficacy of radiotherapy in locally advanced rectal cancer.

Biomed Pharmacother 2020 May 7;125:109954. Epub 2020 Feb 7.

Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China; Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China. Electronic address:

Radiotherapy (RT) is a key component of neoadjuvant chemoradiotherapy to treat locally advanced rectal cancer (LARC). However, the therapeutic effect is limited due to radioresistance. Investigating the biomarkers of radioresistance might assist in the development of more effective therapeutic strategies for LARC.In this study, we investigated the different gene expressions in tumor samples from 110 patients using transcriptome analysis and immunohistochemistry (IHC), and identified serum- and glucocorticoid-regulated kinase 1 (SGK1) as a modulator of LARC radioresistance. We evaluated the impact of genetic and pharmacologic inhibition of the gene associated with radioresistance in vitro and in vivo. We found that the expression of SGK1 was upregulated in non-pathological complete response (non-pCR) patients. A high SGK1 expression was associated with radioresistance, whereas the genetic or pharmacologic inhibition of SGK1 expression reduced the radioresistance. We found that activate transcription factor 3 (ATF3) is a regulator of SGK1 in radioresistance.In conclusion, our findings indicate that SGK1 is a key player in LARC radioresistance, and drives radioresistance in an ATF3 dependent manner, which provides insights for future radio-sensitizer design.
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http://dx.doi.org/10.1016/j.biopha.2020.109954DOI Listing
May 2020

Colorectal cancer, radiotherapy and gut microbiota.

Chin J Cancer Res 2019 Feb;31(1):212-222

Department of Radiation Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.

Colorectal cancer is closely related to inflammation and immune response. Radiotherapy, as a major treatment for colorectal cancer, plays a central role in cancer control. Inflammation caused by ionizing radiation can exert either anti- or pro-tumorigenic effects. Additionally, radiotherapy can elicit an anti-tumor response not only in radiation of target lesions but also in radiation of remote lesions. However, the immune mechanism underlying this effect has not been thoroughly elucidated yet. The combination therapeutic regimen of radiotherapy with other therapeutic methods, including chemotherapy and immunotherapy, has been applied in clinical practice. Meanwhile, radiation toxicity and radiosensitivity have long been problems that affect a patient's quality of life and morbidity. Researchers have found that the abovementioned problems are closely associated with gut microbiota. Here we discuss the impact of immune response induced by radiotherapy on tumor regression and the impact of intestinal flora on the consequent clinical efficacy.
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http://dx.doi.org/10.21147/j.issn.1000-9604.2019.01.16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6433578PMC
February 2019

A Novel Hybrid-Layered Organic Phototransistor Enables Efficient Intermolecular Charge Transfer and Carrier Transport for Ultrasensitive Photodetection.

Adv Mater 2019 Apr 4;31(16):e1900763. Epub 2019 Mar 4.

Materials Interfaces Center, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, P. R. China.

The interfacial charge effect is crucial for high-sensitivity organic phototransistors (OPTs), but conventional layered and hybrid OPTs have a trade-off in balancing the separation, transport, and recombination of photogenerated charges, consequently impacting the device performance. Herein, a novel hybrid-layered phototransistor (HL-OPT) is reported with significantly improved photodetection performance, which takes advantages of both the charge-trapping effect (CTE) and efficient carrier transport. The HL-OPT consisting of 2,7-dioctyl[1]benzothieno[3,2-b][1]benzothiophene (C8-BTBT) as conduction channel, C8-BTBT:[6,6]-phenyl-C -butyric acid methyl ester (PC BM) bulk heterojunction as photoactive layer, and sandwiched MoO interlayer as a charge-transport interlayer exhibits outstanding photodetection characteristics such as a photosensitivity (I /I ) of 2.9 × 10 , photoresponsivity (R) of 8.6 × 10 A W , detectivity (D*) of 3.4 × 10 Jones, and external quantum efficiency of 3 × 10 % under weak light illumination of 32 µW cm . The mechanism and strategy described here provide new insights into the design and optimization of high-performance OPTs spanning the ultraviolet and near infrared (NIR) range as well as fundamental issues pertaining to the electronic and photonic properties of the devices.
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http://dx.doi.org/10.1002/adma.201900763DOI Listing
April 2019

Total mesorectal excision with or without preoperative chemoradiotherapy for resectable mid/low rectal cancer: a long-term analysis of a prospective, single-center, randomized trial.

Cancer Commun (Lond) 2018 12 20;38(1):73. Epub 2018 Dec 20.

Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, P. R. China.

Background: The preliminary results of our phase II randomized trial reported comparable functional sphincter preservation rates and short-term survival outcomes between patients undergoing total mesorectal excision (TME) with or without preoperative concurrent chemoradiotherapy (CCRT). We now report the long-term results after a median follow-up of 71 months.

Methods: Between March 23, 2008 and August 2, 2012, 192 patients with T3-T4 or node-positive, resectable, mid/low rectal adenocarcinoma were randomly assigned to receive TME with or without preoperative CCRT. The following endpoints were assessed: cumulative rates of local recurrence and distant metastasis, disease-free survival (DFS), and overall survival (OS).

Results: The data of 184 eligible patients were analyzed: 94 patients in the TME group and 90 patients in the CCRT + TME group. In the whole cohort, the 5-year DFS and OS rates were 84.8% and 85.1%, respectively. The 5-year DFS rates were 85.2% in the CCRT + TME group and 84.3% in the TME group (P = 0.969), and the 5-year OS rates were 83.5% in the CCRT + TME group and 86.5% in the TME group (P = 0.719). The 5-year cumulative rates of local recurrence were 6.3% and 5.0% (P = 0.681), and the 5-year cumulative rates of distant metastasis were 15.0% and 15.7% (P = 0.881) in the CCRT + TME and TME groups, respectively. No significant improvements in 5-year DFS and OS were observed with CCRT by subgroup analyses.

Conclusions: Both treatment strategies yielded similar long-term outcomes. A selective policy towards preoperative CCRT is thus recommended for rectal cancer patients if high-quality TME surgery and enhanced chemotherapy can be performed. Trial registration ChiCTR-TRC-08000122. Registered 16 July 2008.
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http://dx.doi.org/10.1186/s40880-018-0342-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6302296PMC
December 2018

ypTNM category combined with AJCC tumor regression grade for screening patients with the worst prognosis after neoadjuvant chemoradiation therapy for locally advanced rectal cancer.

Cancer Manag Res 2018 31;10:5219-5225. Epub 2018 Oct 31.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People's Republic of China,

Background: The purpose of this study was to investigate the value of the postsurgical pathological T and N (ypTN) category combined with the American Joint Committee on Cancer-tumor regression grade (AJCC-TRG) in evaluating the prognosis of neoadjuvant chemoradiation therapy (NeoCRT) for locally advanced rectal cancer (LARC) to screen for a subgroup of patients with the worst prognosis.

Patients And Methods: In total, 265 patients with LARC were enrolled in the trial. All patients received NeoCRT. Total mesorectal excision was performed 6-8 weeks after the completion of radiotherapy. The surgical specimens were re-evaluated based on the AJCC-TRG (seventh edition) and the AJCC-tumor-node-metastasis (TNM; seventh edition) systems. We followed up these patients and calculated their overall survival (OS), disease-free survival (DFS), local recurrence-free survival (RFS), and distant metastasis (DM)-free survival (MFS) rates through the Kaplan-Meier analysis. The logrank test was further applied to evaluate the predictive value of the ypTN stage combined with AJCC-TRG for several survival indexes.

Results: The median follow-up period was 65.1 months. The 5-year OS, DFS, RFS, and MFS rates were 79.4%, 68.8%, 94.4%, and 76.5%, respectively. There were significant differences in OS, DFS, and MFS rates among different ypT+AJCC-TRG and ypN+AJCC-TRG subgroups. The 5-year OS, DFS, and MFS rates for ypT3-4+TRG 1 and ypT3-4+TRG2-3 subgroups were 73.9% vs 65.3%, 61.2% vs 52.9%, and 65.0% vs 61.5%, respectively. The 5-year OS, DFS, and MFS rates for ypN1-2+TRG 0-1 and ypN1-2+TRG2-3 subgroups were 64.8% vs 54.1%, 44.9% vs 41.7%, and 61.4% vs 46.3%, respectively.

Conclusion: The ypTNM category combined with the AJCC-TRG can more accurately evaluate the prognosis of patients with LARC and identify the subgroup of patients with the worst prognosis and high risk of developing DM, thereby demonstrating clinical significance in guiding individualized postoperative adjuvant therapy and follow-up for LARC.
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http://dx.doi.org/10.2147/CMAR.S179151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6217173PMC
October 2018

Late Sequelae of Childhood and Adolescent Nasopharyngeal Carcinoma Survivors After Radiation Therapy.

Int J Radiat Oncol Biol Phys 2019 01 20;103(1):45-51. Epub 2018 Sep 20.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China; Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China. Electronic address:

Purpose: The objective of this study was to reveal the long-term sequelae in survivors of childhood and adolescent nasopharyngeal carcinoma after radiation therapy.

Methods And Materials: We reviewed the medical records of patients aged <18 years with nasopharyngeal carcinoma who were treated at Sun Yat-sen University Cancer Center from February 1991 to October 2010. Data concerning clinical characteristics, treatment, outcomes, and late morbidities were extracted. We used χ tests and binary regression analysis to compare the cumulative incidence (CI) of treatment comorbidities among different groups of survivors.

Results: A total of 94 patients survived. They had a median follow-up time of 10 years (5-27 years). Compared with the CI of survivors treated with conventional radiation therapy treatment, the CI of xerostomia, dysphagia, and chronic otitis media was significantly decreased in the survivors treated with intensity modulated radiation therapy treatment. The CI of blurred vision in patients younger than 10 years and in patients 10 to 18 years old were 33.3% and 2.3%, respectively (P = .006). Survivors who received a nasopharynx dose >72 Gy, compared with a nasopharynx dose of 60 to 72 Gy, had a significantly higher CI of hearing loss (P = .008), lalopathy (P = .013), and cranial nerve injury (P = .029). We also had records of height, weight, education level, annual income, marital and fertility status, and menstruation state for 59 of the survivors. Twenty-two percent of the survivors had a body mass index lower than 18.5. Among the female survivors, 11 of 16 (62.5%) had menstrual or fertility problems.

Conclusions: Compared with convention radiation therapy treatment, intensity modulated radiation therapy treatment can potentially ameliorate xerostomia, dysphagia, and chronic otitis media. In addition, patients younger than 10 years had a higher CI of blurred vision. Moreover, a dose of more than 72 Gy to primary tumor increased the CI of hearing loss, lalopathy, and cranial nerve injury.
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http://dx.doi.org/10.1016/j.ijrobp.2018.09.015DOI Listing
January 2019

Analysis of Clinical characteristics to predict pathologic complete response for patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy.

J Cancer 2018 23;9(15):2687-2692. Epub 2018 Jun 23.

Department of Radiation Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China.

To explore clinical characteristics which could be applied to predict pathologic complete response (pCR) for patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy (neo-CRT) and total mesorectal excision (TME). 297 patients with locally advanced rectal cancer (cT3-4 or cN+) who were treated with neo-CRT followed by TME were retrospectively reviewed. Clinical characteristics including age, gender, tumor distance from anus, serum CEA, hemoglobin levels before treatment and clinical TN stage were used to investigate the association with pCR after neo-CRT. Seventy-nine (26.6%) patients achieved pCR after neo-CRT. pCR were achieved in 42 (34.4%) patients in cT1-3 stage and 37 (21.1%) in cT4 stage. pCR rate was 36.4% and 16.4% for patients with pre-treatment serum CEA ≤5.33ng/ml and >5.33ng/ml, respectively. Uni- and multi-variate analyses revealed that pre-treatment serum CEA level ≤5.33ng/ml and clinical T stage, (i.e., cT1-3 versus cT4) were highly correlated with pCR (p < 0.05). Clinical T stage and pre-treatment serum CEA level were strongly associated with pCR for patients with locally advanced rectal cancer treated with neo-CRT followed by TME which could be applied as clinical predictors for pCR.
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http://dx.doi.org/10.7150/jca.25493DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6072814PMC
June 2018

Long-Term Outcome of Oxaliplatin and Capecitabine (XELOX) Concomitant with Neoadjuvant Radiotherapy and Extended to the Resting Period in High Risk Locally Advanced Rectal Cancer.

J Cancer 2018 6;9(8):1365-1370. Epub 2018 Apr 6.

Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, P R. China.

This study aimed at investigating the long-term outcomes of oxaliplatin and capecitabine (XELOX) administered concurrently with preoperative radiation and extended to the resting period in patients with high-risk locally advanced rectal cancer (LARC). From January 2010 to December 2013, 45 patients were recruited. Study treatment consisted two cycles of XELOX regimen concomitant with preoperative radiation and then followed by an additional cycle of XELOX regimen between completion of neoadjuvant radiotherapy and surgery. Disease-free survival (DFS) time and overall survival (OS) time were analyzed. The median follow-up was 51 months. Twelve (26.7%) patients developed local recurrence or distant metastasis, including 10 (22.2%) patients developing distant metastasis only, 1 (2.2%) patient local recurrence only, and 1 (2.2%) patient both local recurrence and distant metastasis. The estimated 3-year DFS and OS was 75.5% (95% CI, 63.0%-88.0%) and 88.6% (95% CI, 98.0%-79.2%), respectively. Receiving adjuvant chemotherapy was a significant predictor for DFS, with hazard ratio 0.24 (95% CI: 0.08-0.74). This intensified strategy with oxaliplatin and capecitabine (XELOX) administered concomitantly with neoadjuvant radiotherapy and then extended to the resting period in high-risk LARC patients is efficient. The long-term outcome is promising. Further study of this strategy is warranted.
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http://dx.doi.org/10.7150/jca.23874DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5929080PMC
April 2018

Cycle number of neoadjuvant chemotherapy might influence survival of patients with T1-4N2-3M0 nasopharyngeal carcinoma.

Chin J Cancer Res 2018 Feb;30(1):51-60

Department of Radiation Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center of Cancer Medicine, Guangzhou 510060, China.

Objective: Stage N2-3 nasopharyngeal carcinoma (NPC) shows a high risk of distant metastasis, which will finally cause death. This study aimed to evaluate the impact of neoadjuvant chemotherapy (NACT) of various cycles before radical radiotherapy on distant metastasis and survival of patients with stage N2-3 diseases.

Methods: In this study, a total of 1,164 consecutive patients with non-metastatic N2-3 NPC were recruited and prospectively observed. Then 231 patients who received NACT of 4 cycles (NACT=4 group) were matched 1:2:1 to 462 patients treated with NACT of 2 cycles (NACT=2 group) and 231 patients treated without NACT (NACT=0 group), according to age, histological subtype, N stage and NACT regimen. Five candidate variables (sex, T stage, concurrent chemotherapy, intensity-modulated radiation therapy and cycle number of NACT) were analyzed for their association with patients' survival.

Results: After matching, the overall survival (OS), disease-free survival (DFS), local-recurrence-free survival (RFS) and distant-metastasis-free survival (MFS) of the NACT=4 group (89.2%, 81.0%, 83.3% and 84.8%, respectively) were better than those of the NACT=2 group (83.3%, 72.5%, 81.2% and 77.9%, respectively) and the NACT=0 group (74.0%, 63.2%, 74.0% and 68.8%, respectively). In multivariate analysis, the cycle number of NACT maintained statistical significance on the OS, DFS, RFS and MFS (all P<0.05).

Conclusions: For N2-3 NPC, cycle number of NACT appeared to be an independent factor associated with an improvement of survival.
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http://dx.doi.org/10.21147/j.issn.1000-9604.2018.01.06DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5842233PMC
February 2018

Early recurrence in patients undergoing curative resection of colorectal liver oligometastases: identification of its clinical characteristics, risk factors, and prognosis.

J Cancer Res Clin Oncol 2018 Feb 11;144(2):359-369. Epub 2017 Nov 11.

State Key Laboratory of Oncology in South China, Department of Colorectal Surgery, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, People's Republic of China.

Purpose: Oligometastatic disease can potentially be cured when an optimal approach is performed. Early recurrence after liver resection is an intractable problem, and the clinical implications remain unknown in colorectal liver oligometastases (CLOM) patients. This study aimed to investigate the clinical characteristics, risk factors, and prognosis related to early recurrence in these patients.

Methods: A total of 307 consecutive patients with CLOM undergoing curative liver resection were retrospectively reviewed between September 1999 and June 2016. Early recurrence was defined as any recurrence or death from CLOM that occurred within 6 months of liver resection.

Results: With a median follow-up time of 31.7 months, the 3-year overall survival (OS) and recurrence-free survival rates were 68.7 and 42.5%, respectively. Forty-nine (16.0%) patients developed early recurrence and showed a poorer 3-year OS than those with non-early recurrence (22.3 vs. 75.8%, P < 0.001) or later recurrence (22.3 vs. 52.8 vs. 63.2%, P < 0.001). Moreover, early recurrence was identified as an independent predictor of 3-year OS [hazard ratio (HR) 6.282; 95% confidence interval (CI) 3.980-9.915, P < 0.001]. In multivariate analysis, a node-positive primary tumor [odds ratio (OR) 2.316; 95% CI 1.097-4.892, P = 0.028) and metastatic diameter > 3 cm (OR 2.560; 95% CI 1.290-5.078; P = 0.007) were shown to be risk factors for early recurrence. The salvage liver resection rate for patients with early recurrence was significantly lower than that for patients with later recurrence (4.1 vs. 19.7%, P = 0.010).

Conclusions: Early recurrence should be investigated in routine clinical practice, even in patients with CLOM after curative liver resection. Detailed preoperative comprehensive measurements might help stratify high-risk patients, and a non-surgical treatment for early recurrence might represent an effective alternative.
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http://dx.doi.org/10.1007/s00432-017-2538-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5794819PMC
February 2018

Interface Energy Alignment of Atomic-Layer-Deposited VO on Pentacene: an in Situ Photoelectron Spectroscopy Investigation.

ACS Appl Mater Interfaces 2017 Jan 5;9(2):1885-1890. Epub 2017 Jan 5.

School of Advanced Materials, Shenzhen Graduate School, Peking University , Shenzhen 518055, China.

Ultrathin atomic-layer-deposited (ALD) vanadium oxide (VO) interlayer has recently been demonstrated for remarkably reducing the contact resistance in organic electronic devices (Adv. Funct. Mater. 2016, 26, 4456). Herein, we present an in situ photoelectron spectroscopy investigation (including X-ray and ultraviolet photoelectron spectroscopies) of ALD VO grown on pentacene to understand the role of the ALD VO interlayer for the improved contact resistance. The in situ photoelectron spectroscopy characterizations allow us to monitor the ALD growth process of VO and trace the evolutions of the work function, pentacene HOMO level, and VO defect states during the growth. The initial VO growth is found to be partially delayed on pentacene in the first ∼20 ALD cycles. The underneath pentacene layer is largely intact after ALD. The ALD VO is found to contain a high density of defect states starting from 0.67 eV below the Fermi level, and the energy level of these defect states is in excellent alignment with the HOMO level of pentacene, which therefore allows these VO defect states to provide an efficient hole-injection pathway at the contact interface.
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http://dx.doi.org/10.1021/acsami.6b12832DOI Listing
January 2017

Severe weight loss during preoperative chemoradiotherapy compromises survival outcome for patients with locally advanced rectal cancer.

J Cancer Res Clin Oncol 2016 Dec 9;142(12):2551-2560. Epub 2016 Sep 9.

Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, People's Republic of China.

Purpose: In addition to tumor factors, poor nutritional status before and during anti-tumor treatment might compromise prognosis in several types of cancer. This study was done to determine the impact of weight loss during preoperative chemoradiotherapy (CRT) on the survival outcome of patients with locally advanced rectal cancer (LARC).

Methods: The retrospective study examined consecutive patients with LARC who underwent preoperative CRT followed by radical resection in a single institute, between 2003 and 2013. Correlation of proportional body mass index (BMI) change after preoperative CRT and patient's demographics, tumor characteristics, treatment parameters, CRT-related toxicity, disease-free survival (DFS) and overall survival (OS) were investigated.

Results: A total of 364 patients were enrolled, and BMI loss was found in 243 patients (66.2 %) after preoperative CRT. Severe weight loss (SWL) was defined as BMI loss ≥7 %. Thirty-nine (10.7 %) cases were enrolled in SWL cohort and found to have higher incidence of diarrhea (P = 0.033), renal disorder (P = 0.033) and grade 3-4 radiation proctitis (P = 0.041). Although no significant difference was found in 3-year DFS, patients in SWL cohort showed significantly worse 3-year OS rate (71.8 vs 88.0 %, P = 0.030) than the others. In univariate analysis, BMI loss ≥7 %, completed dose of preoperative chemotherapy, pathologic T and N stages were correlated with OS (all P < 0.05). In multivariable analysis, BMI loss ≥7 % (HR 1.984; 95 % CI 1.061-3.709; P = 0.032) remained the independent prognostic factor for OS.

Conclusions: Our results demonstrate that SWL during preoperative CRT indeed compromises survival outcome in patients with LARC. Routine nutritional monitoring and nutritional support during preoperative CRT are suggested as the integral part of the multidisciplinary approach for these patients.
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http://dx.doi.org/10.1007/s00432-016-2225-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5095158PMC
December 2016

Pathological Assessment of Rectal Cancer after Neoadjuvant Chemoradiotherapy: Distribution of Residual Cancer Cells and Accuracy of Biopsy.

Sci Rep 2016 10 10;6:34923. Epub 2016 Oct 10.

Department of Radiation Oncology, Sun Yat-sen University Cancer Center, China.

We investigated the distribution of residual cancer cells (RCCs) within different layers of the bowel wall in surgical specimens and the value of biopsies of primary rectal lesion after preoperative volumetric modulated arc therapy (VMAT) with concurrent chemotherapy in patients with rectal cancer. Between April 2011 and April 2013, 178 patients with rectal cancer who received preoperative VMAT, concurrent chemotherapy, and surgery were evaluated; 79 of the patients received a biopsy of the primary lesion after chemoradiotherapy and prior to surgery. The distribution of RCCs in the surgical specimens and the sensitivity and specificity of the biopsy of primary rectal lesions for pathological response were evaluated. Fifty-two patients had a complete pathological response in the bowel wall. Of the 120 patients with ypT2-4, the rate of detection of RCCs in the mucosa, submucosa, and muscularis propria was 20%, 36.7%, 69.2%, respectively. The sensitivity and specificity of biopsies of primary rectal lesions was 12.9% and 94.1%, respectively. After chemoradiotherapy, the RCCs were primarily located in the deeper layers of the bowel wall, and the biopsy results for primary rectal lesions were unreliable due to poor sensitivity.
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http://dx.doi.org/10.1038/srep34923DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5056357PMC
October 2016

Clinical factors of post-chemoradiotherapy as valuable indicators for pathological complete response in locally advanced rectal cancer.

Clinics (Sao Paulo) 2016 Aug;71(8):449-54

Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Department of Colorectal Surgery.

Objectives: Pathological complete response has shown a better prognosis for patients with locally advanced rectal cancer after preoperative chemoradiotherapy. However, correlations between post-chemoradiotherapy clinical factors and pathologic complete response are not well confirmed. The aim of the current study was to identify post-chemoradiotherapy clinical factors that could serve as indicators of pathologic complete response in locally advanced rectal cancer.

Methods: This study retrospectively analyzed 544 consecutive patients with locally advanced rectal cancer treated at Sun Yat-sen University Cancer Center from December 2003 to June 2014. All patients received preoperative chemoradiotherapy followed by surgery. Univariate and multivariate regression analyses were performed to identify post-chemoradiotherapy clinical factors that are significant indicators of pathologic complete response.

Results: In this study, 126 of 544 patients (23.2%) achieved pathological complete response. In multivariate analyses, increased pathological complete response rate was significantly associated with the following factors: post-chemoradiotherapy clinical T stage 0-2 (odds ratio=2.098, 95% confidence interval=1.023-4.304, p=0.043), post-chemoradiotherapy clinical N stage 0 (odds ratio=2.011, 95% confidence interval=1.264-3.201, p=0.003), interval from completion of preoperative chemoradiotherapy to surgery of >7 weeks (odds ratio=1.795, 95% confidence interval=1.151-2.801, p=0.010) and post-chemoradiotherapy carcinoembryonic antigen ≤2 ng/ml (odds ratio=1.579, 95% confidence interval=1.026-2.432, p=0.038).

Conclusions: Post-chemoradiotherapy clinical T stage 0-2, post-chemoradiotherapy clinical N stage 0, interval from completion of chemoradiotherapy to surgery of >7 weeks and post-chemoradiotherapy carcinoembryonic antigen ≤2 ng/ml were independent clinical indicators for pathological complete response. These findings demonstrate that post-chemoradiotherapy clinical factors could be valuable for post-operative assessment of pathological complete response.
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http://dx.doi.org/10.6061/clinics/2016(08)07DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4975783PMC
August 2016

[Short-term efficacy comparison between preoperative three dimensional conformal radiotherapy and volumetric modulated arc therapy concurrently combined with chemotherapy in the treatment of locally advanced rectal carcinoma].

Zhonghua Wei Chang Wai Ke Za Zhi 2016 Jul;19(7):769-75

Department of radiotherapy, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center of Cancer Medicine, Guangzhou 510060, China.

Objective: To compare the short-term efficacy and treatment-related adverse reaction between preoperative three dimensional conformal radiotherapy (3D-CRT) and volumetric modulated arc therapy (VMAT) concurrently combined with chemotherapy in the treatment of locally advanced rectal carcinoma (LARC).

Methods: Clinical data of 334 patients with LARC undergoing preoperative 3D-CRT(172 cases) or VMAT(162 cases) with concurrent Xelox chemotherapy (main protocol: capecitabine plus oxaliplatin) and surgery in Sun Yat-sen University Cancer Center from May 2007 to April 2013 were retrospectively analyzed. The total radiation dose of VMAT group was: 50 Gy/2.0 Gy per fraction ×23 fractions for planning target volume 1(PTV1) and 46 Gy/1.84 Gy per fraction ×25 fractions for PTV2; the total radiation dose of 3D-CRT group was: 46 Gy/2.0 Gy per fraction ×23 fractions for PTV. The treatment-related adverse reaction of both groups during chemoradiotherapy was measured according to the criteria of Common Terminology Criteria for Adverse Events v3.0 (CTCAE 3.0). Rate of adverse reaction and short-term efficacy between 3D-CRT and VMAT group were compared, in terms of radiotherapy break, hematological and non-hematological toxicity, average duration of surgery and perioperative hospitalization, intraoperative blood loss, surgical procedures, R0 excision, sphincter preservation, postoperative complications, pathological complete response (pCR), and postoperative pathological staging.

Results: There were no significant differences in baseline clinical parameters between 3D-CRT and VMAT group (all P>0.05), except for the distance from lower tumor margin to anal verge (P=0.009). The median radiation dose for all the patients was 46 (45 to 70) Gy. There was no significant difference in the rate of radiotherapy cessation between 3D-CRT and VMAT group [1.7%(3/172) vs. 1.2%(2/162), P=1.000]. During concurrent chemotherapy, incidences of grade 2 to 3 hematological toxicities, grade 2 diarrhea, and grade 3 non-hematological toxicities were not significantly different(all P>0.05), while in grade 2 non-hematological toxicities, ratio of radiodermatitis and hand-foot syndrome was higher in VMAT group as compared to 3D-CRT group [25.9%(42/162) vs. 10.5%(18/172), P=0.000; 3.7%(6/162) vs. 0, P=0.012]. There was no grade 4 adverse event in both groups. Surgical procedure, average duration of surgery, R0 excision, anus preservation, postoperative complications, pCR, and postoperative pathological staging were not significantly different(all P>0.05). As compared to 3D-CRT group, VMAT group had less intraoperative blood loss [(114.6±100) ml vs. (169±143.9) ml, P<0.001] and shorter perioperative hospitalization [16(8 to 84) d vs. 20(10 to 47) d, P<0.001]. There was no death case in two groups within 30 days after operation.

Conclusions: Compared with 3D-CRT technique, preoperative VMAT technique can not significantly reduce the incidence of treatment-related adverse reaction and improve the short-term efficacy in the treatment of LARC.
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July 2016

Can an IL13 -1112 C/T (rs1800925) polymorphism predict responsiveness to neoadjuvant chemoradiotherapy and survival of Chinese Han patients with locally advanced rectal cancer?

Oncotarget 2016 Jun;7(23):34149-57

Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.

We sought to determine whether a polymorphism in the Interleukin 13 gene (IL13), 1112 C/T (rs1800925) predicts responsiveness to neoadjuvant chemoradiotherapy (neoCRT) and prognosis in Chinese Han patients with locally advanced rectal cancer (LARC). Pre-treatment biopsies of primary rectal lesion and surgical specimens were collected from 58 patients with LARC, who were treated with neoCRT and surgery. Tumor DNA was extracted from these biopsies and sequenced to analyze the rs1800925 polymorphism. The tumor response to neoCRT was categorized using a tumor regression grade (TRG, 0-2 were poor responders; 3-4 were good responders). Analyses of progression free survival (PFS) and overall survival (OS) were carried out using the Kaplan-Meier method. Of the forty-six patients for whom tumor DNA was successfully sequenced, 23 were good responders to neoCRT (11 patients with a pathological complete response, i.e. pCR) and the other 23 were poor responders. Good and poor responders were equally likely to have a C/C genotype at rs1800925 (73.9%) as a T/T or C/T genotype (26.1%). There were no differences between the C/C and T/T+C/T genotypes with respect to the ypT0-2 ratio (38.2% vs. 41.7%, P = 1.0) , ypN0 nodal status (67.6% vs. 50.0%, P= 0.314), 6-year PFS (67.6% vs. 50%, P=0.274), or 6-year OS (76.5% vs. 66.7%, P=0.441). Thus, the IL13-1112 C/T (rs1800925) polymorphism does not predict responsiveness to neoCRT or prognosis of Chinese Han patients with LARC.
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http://dx.doi.org/10.18632/oncotarget.9178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5085143PMC
June 2016

Predictive value of APAF-1 and COX-2 expression in pathologic complete response to neoadjuvant chemoradiotherapy for patients with locally advanced rectal adenocarcinoma.

Oncotarget 2016 Jun;7(23):35233-40

Department of Radiation Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China.

Purpose: To investigate predictive value of APAF-1 and COX-2 expression in pathologic complete response (pCR) for patients with rectal adenocarcinoma (RAC) who were treated with neoadjuvant chemoradiotherapy (neo-CRT) followed by total mesorectal excision (TME).  

Materials And Methods: Immunohistochemistry assay was used to detect expression of APAF-1 and COX-2 in paraffin-wax embedded tissues obtained before neo-CRT for patients with RAC. A 5-point tumor-regression grade (TRG) based on the ratio of residual tumor to fibrosis according to Dworak's scoring system was used to assess neo-CRT response. The relationship between expression of APAF-1 and COX-2 genes and pCR was explored.

Results: pCR (TRG4) was observed in 23 patients (28.0%). pCR were more likely to be achieved for those with APAF-1 over-expression or lower expression of COX-2. pCR rate in patients with combination of high APAF-1 and low COX-2 expression was 56.0%, significantly higher than those with other combination of APAF1 and COX-2 expression. Multivariate analysis showed that over-expression of APAF-1 and suppressed expression of COX-2 were independent predictive factors for pCR.

Conclusion: Immunohistochemical evaluation of APAF-1 and COX-2 expression on pretreatment specimen may be used to predict pCR to neo-CRT in patients with RAC. The potential of the markers in monitoring pCR patient merits further investigation.
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http://dx.doi.org/10.18632/oncotarget.9125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5085224PMC
June 2016
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