Publications by authors named "Yong-Heng Li"

19 Publications

  • Page 1 of 1

Patterns of failure and implications for clinical target volume definition of locally advanced T4b rectal cancer identified with magnetic resonance imaging and treated using neoadjuvant chemoradiotherapy and surgery.

Radiother Oncol 2021 Aug 12;161:132-139. Epub 2021 Jun 12.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, PR China. Electronic address:

Background And Purpose: Elective irradiation of the external iliac lymph nodes (EIN) has always been advocated for T4b rectal cancer with anterior organ invasion without convincing evidence. This study aimed to explore the patterns of treatment failure for locally advanced T4b rectal cancer treated using neoadjuvant chemoradiotherapy (NCRT) and surgery. This information may help to clarify whether the current definition of the clinical target volume (CTV) is still appropriate.

Materials And Methods: We retrospectively analyzed data from 126 patients with locally advanced T4b rectal cancer who received NCRT, without elective EIN irradiation, followed by surgery between January 2010 and October 2018. Pretreatment magnetic resonance imaging was used to identify the T4b disease in all cases. The locoregional recurrence (LRR) rate and EIN failure rate were evaluated, and the LRR locations were identified using a three-dimensional model.

Results: After a median follow-up of 53.9 months, LRR occurred in 11.1% of patients (14/126). All LRRs were located in the previously irradiated fields and below the S2-S3 junction. The EIN failure rate was 0.8% (1/126) among all patients and 1.8% (1/56) in the group with anterior genitourinary organ invasion. The estimated 4-year distant relapse-free survival, disease-free survival and overall survival were 79.3%, 73.2% and 86.9%, respectively.

Conclusions: It may be feasible to exclude the external iliac region from the CTV during NCRT for locally advanced T4b rectal cancer. However, further studies are needed to clarify whether the cranial border of the CTV can be lowered.
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http://dx.doi.org/10.1016/j.radonc.2021.06.017DOI Listing
August 2021

Preliminary results of simultaneous integrated boost intensity-modulated radiation therapy based neoadjuvant chemoradiotherapy on locally advanced rectal cancer with clinically suspected positive lateral pelvic lymph nodes.

Ann Transl Med 2021 Feb;9(3):217

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital and Institute, Beijing, China.

Background: Lateral pelvic lymph node (LPLN) is approximately 11-14% and always associated with poorer prognosis. This study investigated the efficacy and safety of simultaneous integrated boost intensity-modulated radiation therapy (SIB-IMRT) based on neoadjuvant chemoradiotherapy (NCRT) on locally advanced rectal cancer (LARC) patients with clinically suspected positive LPLNs.

Methods: We retrospectively screened distal LARC patients with NCRT in our center from May 2016 and June 2019. The diagnostic criteria of positive LPLN were nodes of over 7 mm in short axis and irregular border or mixed-signal intensity. All patients with clinically suspected positive LPLN received 56-60 Gy SIB-IMRT in the LPLN area. Concurrent chemotherapy regimens were capecitabine as monotherapy treatment or in combination with oxaliplatin. The toxicities, local-regional recurrence (LRR), and disease-free survival (DFS) were investigated.

Results: Fifty-two eligible patients with clinically suspected positive LPLN were screened and analyzed. The median distance from the distal tumor to the anal verge was 4 cm (range, 0-8 cm), while magnetic resonance imaging (MRI) analysis revealed the median short diameter of the pelvic LPLN to be 8 mm (range, 7-20 mm). There were 28 (53.8%) mesorectal fascia (MRF) positive and 22 (42.3%) extramural venous invasion (EMVI) positive patients. A radiotherapy dose of 41.8 Gy was administered to the pelvic area, while the LPLN received a median SIB dose of 60.0 Gy (range, 56-60 Gy) across 22 fractions. Synchronous capecitabine with or without oxaliplatin was administered during radiotherapy. In summary, 15 (28.8%) patients displayed grade 2-3 radiation-related toxicity, 8 (15.4%) patients underwent additional LPLN dissection, and positive nodes (26 nodes in total) were not observed. One patient suffered a LLR in the presacral region. The median follow-up duration was 21.2 months (range, 4.7-45.0 months), while the duration of 1- and 2-year DFS were 89.9% and 74.6%, respectively. Patients did not display LPLN recurrence.

Conclusions: The safety and efficacy of SIB-IMRT on clinically suspected positive LPLN of LARC patients were deemed acceptable. Patients did not exhibit in-field LPLN recurrence after NCRT combined with single total mesorectal excision (TME).
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http://dx.doi.org/10.21037/atm-20-4040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940951PMC
February 2021

The watch-and-wait strategy versus surgical resection for rectal cancer patients with a clinical complete response after neoadjuvant chemoradiotherapy.

Radiat Oncol 2021 Jan 19;16(1):16. Epub 2021 Jan 19.

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

Background: The watch-and-wait strategy offers a non-invasive therapeutic alternative for rectal cancer patients who have achieved a clinical complete response (cCR) after chemoradiotherapy. This study aimed to investigate the long-term clinical outcomes of this strategy in comparation to surgical resection.

Methods: Stage II/III rectal adenocarcinoma patients who received neoadjuvant chemoradiotherapy and achieved a cCR were selected from the databases of three centers. cCR was evaluated by findings from digital rectal examination, colonoscopy, and radiographic images. Patients in whom the watch-and-wait strategy was adopted were matched with patients who underwent radical resection through 1:1 propensity score matching analyses. Survival was calculated and compared in the two groups using the Kaplan-Meier method with the log rank test.

Results: A total of 117 patients in whom the watch-and-wait strategy was adopted were matched with 354 patients who underwent radical resection. After matching, there were 94 patients in each group, and no significant differences in term of age, sex, T stage, N stage or tumor location were observed between the two groups. The median follow-up time was 38.2 months. Patients in whom the watch-and-wait strategy was adopted exhibited a higher rate of local recurrences (14.9% vs. 1.1%), but most (85.7%) were salvageable. Three-year non-regrowth local recurrence-free survival was comparable between the two groups (98% vs. 98%, P = 0.506), but the watch-and-wait group presented an obvious advantage in terms of sphincter preservation, especially in patients with a tumor located within 3 cm of the anal verge (89.7% vs. 41.2%, P < 0.001). Three-year distant metastasis-free survival (88% in the watch-and-wait group vs. 89% in the surgical group, P = 0.874), 3-year disease-specific survival (99% vs. 96%, P = 0.643) and overall survival (99% vs. 96%, P = 0.905) were also comparable between the two groups, although a higher rate (35.7%) of distant metastases was observed in patients who exhibited local regrowth in the watch-and-wait group.

Conclusion: The watch-and-wait strategy was safe, with similar survival outcomes but a superior sphincter preservation rate as compared to surgery in rectal cancer patients achieving a cCR after neoadjuvant chemoradiotherapy, and could be offered as a promising conservative alternative to invasive radical surgery.
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http://dx.doi.org/10.1186/s13014-021-01746-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816381PMC
January 2021

Radiosensitivity of Cancer Stem Cells in Lung Cancer Cell Lines.

J Vis Exp 2019 08 21(150). Epub 2019 Aug 21.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital and Institute;

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.
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http://dx.doi.org/10.3791/60046DOI Listing
August 2019

Calcium channel α2δ1 subunit (CACNA2D1) enhances radioresistance in cancer stem-like cells in non-small cell lung cancer cell lines.

Cancer Manag Res 2018 26;10:5009-5018. Epub 2018 Oct 26.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital and Institute, Beijing, China,

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 ) 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. -knockdown and -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. knockdown in A549 cells enhanced radiosensitivity, whereas 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.
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http://dx.doi.org/10.2147/CMAR.S176084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6208517PMC
October 2018

Pattern and Management of Recurrence of Mid-Low Rectal Cancer After Neoadjuvant Intensity-Modulated Radiotherapy: Single-Center Results of 687 Cases.

Clin Colorectal Cancer 2018 06 7;17(2):e307-e313. Epub 2018 Mar 7.

Department of Gastrointestinal Surgery, Peking University Cancer Hospital, Beijing, PR China.

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.
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http://dx.doi.org/10.1016/j.clcc.2018.01.006DOI Listing
June 2018

Recombinant Adenovirus-p53 Gene Therapy for Advanced Unresectable Soft-Tissue Sarcomas.

Hum Gene Ther 2018 06 2;29(6):699-707. Epub 2018 Mar 2.

1 Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital, Beijing Cancer Hospital and Institute , Beijing, P.R. China.

Patients with unresectable advanced soft-tissue sarcomas (STS) receiving radiotherapy or/and chemotherapy still have a poor prognosis. This study aimed to evaluate retrospectively the efficacy and safety of recombinant adenovirus-p53 (rAd-p53) gene therapy combined with radiotherapy and hyperthermia for advanced STS. A total of 71 patients with advanced unresectable STS treated at the authors' center from April 2007 to November 2014 were included. Of these 71 patients, 36 cases received rAd-p53 therapy combined with radiotherapy and hyperthermia (p53 group), while 35 cases received radiotherapy and hyperthermia alone (control group). Short-term therapeutic efficacies, long-term survival outcomes, and adverse events were evaluated and compared between groups. Compared to the control group, the p53 group had a significantly higher disease control rate (83.33% vs. 54.29%; p = 0.008) and a lower progressive disease rate (16.67% vs. 45.71%; p = 0.018). In addition, rAd-p53 treatment significantly improved the progression-free survival and overall survival of STS patients. Cox regression indicated that rAd-p53 treatment significantly reduced the risks for disease progression or death event for STS patients. Furthermore, there was no significant difference in all adverse events, except for transient fever, which occurred in 89% of patients with rAd-p53 therapy. rAd-p53 combined with radiotherapy and hyperthermia can effectively improve the therapeutic efficacy and survival outcomes in patients with advanced unresectable STS, providing a new therapeutic strategy.
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http://dx.doi.org/10.1089/hum.2017.103DOI Listing
June 2018

Associations of tumor regression grade with outcomes in patients with locally advanced rectal cancer treated with preoperative two-week course of radiotherapy.

Oncotarget 2017 Nov 26;8(59):100165-100175. Epub 2017 Oct 26.

Department of Radiation Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education /Beijing), Peking University Cancer Hospital & Institute, Beijing, China.

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.
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http://dx.doi.org/10.18632/oncotarget.22118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5725010PMC
November 2017

Intensity-modulated radiation therapy for pelvic oligo-recurrence from rectal cancer: long-term results from a single institution.

Am J Transl Res 2016 15;8(2):1265-72. Epub 2016 Feb 15.

Department of Radiation Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute Beijing, 100142, P.R. China.

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.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4846970PMC
May 2016

Intermediate Neoadjuvant Radiotherapy Combined With Total Mesorectal Excision for Locally Advanced Rectal Cancer: Outcomes After a Median Follow-Up of 5 Years.

Clin Colorectal Cancer 2016 Jun 22;15(2):152-7. Epub 2015 Oct 22.

Department of Gastrointestinal Surgery, Peking University Cancer Hospital and Institute, Beijing, People's Republic of China. Electronic address:

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.
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http://dx.doi.org/10.1016/j.clcc.2015.10.001DOI Listing
June 2016

Efficacy and safety of neoadjuvant intensity-modulated radiotherapy with concurrent capecitabine for locally advanced rectal cancer.

Dis Colon Rectum 2015 Feb;58(2):186-92

1Department of Colorectal Surgery, Peking University Cancer Hospital, Beijing, People's Republic of China 2Department of Gastrointestinal Surgery, Peking University Cancer Hospital, Beijing, People's Republic of China 3Department of Pathology, Peking University Cancer Hospital, Beijing, People's Republic of China 4Department of Radiation Oncology, Peking University Cancer Hospital, Beijing, People's Republic of China 5Department of Radiology, Peking University Cancer Hospital, Beijing, People's Republic of China.

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.
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http://dx.doi.org/10.1097/DCR.0000000000000294DOI Listing
February 2015

Two-week Course of Preoperative Radiotherapy for Locally Advanced Rectal Adenocarcinoma: 8 Years' Experience in a Single Institute.

Am J Clin Oncol 2017 Jun;40(3):266-273

Departments of *Radiation Oncology ‡Colorectal Surgery, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University School of Oncology, Peking University Cancer Hospital, Beijing Cancer Hospital and Institute, Beijing †Department of Radiation Oncology, Teaching Hospital of Fujian Medical University, Fujian Provincial Cancer Hospital, Fuzhou, China §Department of Radiation Oncology, University of Nebraska Medical Center, Omaha, NE.

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.
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http://dx.doi.org/10.1097/COC.0000000000000142DOI Listing
June 2017

[Comparison of two different chemotherapy regimens for concurrent chemoradiotherapy in stage Ib2 to IVa squamous cell carcinoma of the uterine cervix].

Zhonghua Fu Chan Ke Za Zhi 2013 Oct;48(10):763-7

Email:

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.
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October 2013

[Clinical observation of accelerated partial-breast intensity-modulated radiotherapy in patients with early-stage breast cancer after breast-conserving surgery].

Zhonghua Yi Xue Za Zhi 2013 Mar;93(12):924-6

Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing, China.

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.
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March 2013

Volumetric-modulated arc therapy vs. c-IMRT in esophageal cancer: a treatment planning comparison.

World J Gastroenterol 2012 Oct;18(37):5266-75

Department of Radiotherapy, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing 100142, China.

Aim: To compare the volumetric-modulated arc therapy (VMAT) plans with conventional sliding window intensity-modulated radiotherapy (c-IMRT) plans in esophageal cancer (EC).

Methods: Twenty patients with EC were selected, including 5 cases located in the cervical, the upper, the middle and the lower thorax, respectively. Five plans were generated with the eclipse planning system: three using c-IMRT with 5 fields (5F), 7 fields (7F) and 9 fields (9F), and two using VMAT with a single arc (1A) and double arcs (2A). The treatment plans were designed to deliver a dose of 60 Gy to the planning target volume (PTV) with the same constrains in a 2.0 Gy daily fraction, 5 d a week. Plans were normalized to 95% of the PTV that received 100% of the prescribed dose. We examined the dose-volume histogram parameters of PTV and the organs at risk (OAR) such as lungs, spinal cord and heart. Monitor units (MU) and normal tissue complication probability (NTCP) of OAR were also reported.

Results: Both c-IMRT and VMAT plans resulted in abundant dose coverage of PTV for EC of different locations. The dose conformity to PTV was improved as the number of field in c-IMRT or rotating arc in VMAT was increased. The doses to PTV and OAR in VMAT plans were not statistically different in comparison with c-IMRT plans, with the following exceptions: in cervical and upper thoracic EC, the conformity index (CI) was higher in VMAT (1A 0.78 and 2A 0.8) than in c-IMRT (5F 0.62, 7F 0.66 and 9F 0.73) and homogeneity was slightly better in c-IMRT (7F 1.09 and 9F 1.07) than in VMAT (1A 1.1 and 2A 1.09). Lung V30 was lower in VMAT (1A 12.52 and 2A 12.29) than in c-IMRT (7F 14.35 and 9F 14.81). The humeral head doses were significantly increased in VMAT as against c-IMRT. In the middle and lower thoracic EC, CI in VMAT (1A 0.76 and 2A 0.74) was higher than in c-IMRT (5F 0.63 Gy and 7F 0.67 Gy), and homogeneity was almost similar between VMAT and c-IMRT. V20 (2A 21.49 Gy vs. 7F 24.59 Gy and 9F 24.16 Gy) and V30 (2A 9.73 Gy vs. 5F 12.61 Gy, 7F 11.5 Gy and 9F 11.37 Gy) of lungs in VMAT were lower than in c-IMRT, but low doses to lungs (V5 and V10) were increased. V30 (1A 48.12 Gy vs. 5F 59.2 Gy, 7F 58.59 Gy and 9F 57.2 Gy), V40 and V50 of heart in VMAT was lower than in c-IMRT. MUs in VMAT plans were significantly reduced in comparison with c-IMRT, maximum doses to the spinal cord and mean doses of lungs were similar between the two techniques. NTCP of spinal cord was 0 for all cases. NTCP of lungs and heart in VMAT were lower than in c-IMRT. The advantage of VMAT plan was enhanced by doubling the arc.

Conclusion: Compared with c-IMRT, VMAT, especially the 2A, slightly improves the OAR dose sparing, such as lungs and heart, and reduces NTCP and MU with a better PTV coverage.
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http://dx.doi.org/10.3748/wjg.v18.i37.5266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3468860PMC
October 2012

[Incidence and risk factors of amputation among inpatients with diabetic foot].

Zhonghua Yi Xue Za Zhi 2012 Jun;92(24):1686-9

Division of Endocrinology & Metabolism, Diabetic Foot Care Center, West China Hospital, Sichuan University, Chengdu 610041, China.

Objective: To evaluate the incidence and risk factors of lower extremity amputation among inpatients with diabetic foot.

Methods: For this retrospective study, a total of 685 inpatients with diabetic foot (Wagner grade 1-5) admitted at a multi-disciplinary Diabetic Foot Care Center, West China Hospital, Sichuan University during January 1, 2005 and June 30, 2011. The data of each patient including clinical information, laboratory results and final outcome were collected and analyzed. They were divided into non-amputated and amputated groups. And the latter included minor and major amputation groups according to amputation site.

Results: The overall amputation rate was 11.4% in diabetic foot inpatients. The incidences of minor amputation and major amputation were 5.4% and 6.0% respectively. 17.9% of amputated patients experienced a second amputation. The amputated patients had a longer hospitalized stay, higher counts of white blood cells and neutrophils, greater HbA1c and lower serum levels of hemoglobin and albumin than the non-amputation patients (P < 0.05). The prevalence of diabetic peripheral neuropathy was significantly higher in the amputation group than that in the non-amputation group (P < 0.05). However, no difference existed between the minor and major amputation groups (P > 0.05). Ankle brachial index (ABI) in the amputation group was significantly lower than that in the non-amputation group (0.41 ± 0.25 vs 0.91 ± 0.36, P < 0.01). Minor and major amputation inpatients had similar ABI (0.43 ± 0.24 vs 0.39 ± 0.26, P = 0.087). Ordinal regression showed that HbA1c (P = 0.015), ABI (P = 0.016), history of amputation (P < 0.01) and Wagner grade of diabetic foot (P < 0.01) were the independent risk factors of amputation.

Conclusions: Diabetic foot inpatients have a higher rate of lower extremity amputation. The risk factors of amputation include HbA1c, ABI, history of amputation and Wagner grade of diabetic foot. And diabetic peripheral neuropathy, ischemia of lower limbs (especially peripheral arterial diseases below knees), infection and nutritional state are closely associated with amputation of diabetic foot inpatients.
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June 2012

Preoperative concomitant boost intensity-modulated radiotherapy with oral capecitabine in locally advanced mid-low rectal cancer: a phase II trial.

Radiother Oncol 2012 Jan 6;102(1):4-9. Epub 2011 Sep 6.

Department of Radiation Oncology, Beijing Cancer Hospital and Institute, People's Republic of China.

Purpose: We aimed to assess the safety and efficacy of preoperative intensity-modulated radiotherapy (IMRT) with oral capecitabine in patients with locally advanced mid-low rectal cancer using a concomitant boost technique.

Materials And Methods: Patients with resectable locally advanced mid-low rectal cancer (node-negative ≥T3 or any node-positive tumor) were eligible. The eligible patients received IMRT to 2 dose levels simultaneously (50.6 and 41.8 Gy in 22 fractions) with concurrent capecitabine 825 mg/m(2) twice daily 5 days/week. The primary end point included toxicity, postoperative complication, and pathological complete response rate (ypCR). The secondary endpoints included local recurrence rate, progression-free survival (PFS), and overall survival (OS).

Results: Sixty-three eligible patients were enrolled; five patients did not undergo surgery. Of the 58 patients evaluable for pathologic response, the ypCR rate was 31.0% (95% CI 19.1-42.9). Grade 3 toxicities included diarrhea (9.5%), radiation dermatitis (3.2%), and neutropenia (1.6%). There was no Grade 4 toxicity reported. Four (6.9%) patients developed postoperative complications. Two-year local recurrence rate, PFS, and OS were 5.7%, 90.5%, and 96.0%, respectively.

Conclusions: The design of preoperative concurrent boost IMRT with oral capecitabine could achieve high rate of ypCR with an acceptable toxicity profile.
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http://dx.doi.org/10.1016/j.radonc.2011.07.030DOI Listing
January 2012

Combination of Recombinant Adenovirus-p53 with Radiochemotherapy in Unresectable Pancreatic Carcinoma.

Chin J Cancer Res 2011 Sep;23(3):194-200

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Radiotherapy, Peking University School of Oncology, Beijing Cancer Hospital & Institute, Beijing 100142, China.

Objective: To assess the safety and efficacy of the combination of recombinant adenovirus-p53 (rAd-p53) with radiochemotherapy for treating unresectable pancreatic carcinoma.

Methods: The eligible patients received concurrent rAd-p53 intratumoral injection and radiochemotherapy. Intratumoral injection of rAd-p53 was guided by B ultrasound. Radiochemotherapy consisted of intensity-modulated radiotherapy (IMRT) at two dose levels and intravenous gemcitabine (Gem). For radiotherapy, gross target volume (GTV) and clinical target volume (CTV) were 55-60 Gy and 45-55 Gy in 25-30 fractions, respectively. Concurrent intravenous gemcitabine was administered at 350 mg/m(2), weekly, for 6 weeks. The primary end points included toxicity, clinical benefit response (CBR) and disease control rate (DCR). The secondary end points included progression-free survival (PFS) and overall survival (OS).

Results: Fifteen eligible patients were enrolled. Eight patients (53.3%) were evaluated as CBR and 12 (80%) achieved DCR. The median PFS and OS were 6.7 and 13.8 months, respectively. One-year PFS and OS were 40.0% and 51.1%, respectively. There were 8 (53.3%) patients reported grade 3 toxicities including neutropenia (6 patients, 40%), fever (1 patient, 6.7%) and fatigue (1 patient, 6.7%). There was no grade 4 toxicity reported.

Conclusion: Combination of rAd-p53 in unresectable pancreatic carcinoma showed encouraging efficacious benefit and was well tolerated. Long-term follow-up is needed to confirm the improvement of PFS and OS.
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http://dx.doi.org/10.1007/s11670-011-0194-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3587558PMC
September 2011

[Estimating intraday blood glucose variability through self-monitoring of blood glucose in people with impaired glucose tolerance and type 2 diabetes].

Sichuan Da Xue Xue Bao Yi Xue Ban 2011 Jan;42(1):95-100

Division of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu 610041, China.

Objective: To investigate the associations between the patterns of change of self-monitored blood glucose (SMBG) and the parameters of intraday blood glucose variability [mean absolute glucose excursions (MAGE), mean postprandial glucose excursion (MPPGE) and standard deviation of blood glucose (sBG)] measured by the continuous glucose monitoring system.

Methods: A 72-hour continuous glucose monitoring was performed in a sample 105 people with impaired glucose tolerance (IGR, n=51) and newly-diagnosed type 2 diabetes mellitus (T2DM, n=54) to calculate MAGE, MPPGE and sBG. Meanwhile, fingertip blood glucose self-monitoring was performed to determine fasting blood glucose (FBG), blood glucose after breakfast (BG(AB)), blood glucose before lunch (BG(BL)), blood glucose after lunch (BG(AL)), blood glucose before supper (BG(BS)), blood glucose after supper (BG(AS)), and blood glucose before sleeping (BG(BR)) at the same period of time. Multiple stepwise regression analysis was performed to generate equations for predicting MAGE, MPPGE and sBG with age and the self-monitoring blood glucose parameters in 80% of the subjects (41 IGR and 44 T2DM, randomly selected from the overall sample). These equations were then cross-validated in the remaining 20% subjects (10 IGR and 10 T2DM).

Results: BG(AA), BG(AB), BGAL and FBG entered into the regression equations predicting MAGE, sBG and MPPGE for the IGR subject, while age only entered into the regression equations predicting MPPGE and sBG. For the subjects with T2DM, BG(AS), BG(AL) and age entered into the equation predicting MAGE; BG(AS), BG(AL), BG(BL) and BG(BS) entered into the equation predicting MPPGE; BG(AS), BG(AL) and FBG entered into the equation predicting sBG. The cross-validation study showed that the differences between predicted and observed values of MAGE in the subjects with IGR and T2DM were 4.1% and 8.2%, respectively; the differences between predicted and observed values of MPPGE in the subjects with IGR and T2DM were 23.1% and 1.3%, respectively; and the differences between predicted and observed values of sBG in the subjects with IGR and T2DM were 1.2% and 6.8%, respectively. Except for MPPGE in the subjects with IGR, the goodness of fit between predicted and observed values were good.

Conclusion: The MAGE and sBG in people with IGR and the MAGE, MPPGE and sBG in patients with T2DM can be well predicted with age and self-monitored blood glucose.
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January 2011
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