Publications by authors named "Shang-Wen Chen"

76 Publications

Prediction of Neoadjuvant Chemoradiotherapy Response in Rectal Cancer with Metric Learning Using Pretreatment 18F-Fluorodeoxyglucose Positron Emission Tomography.

Cancers (Basel) 2021 Dec 17;13(24). Epub 2021 Dec 17.

Center of Augmented Intelligence in Healthcare, China Medical University Hospital, Taichung 404, Taiwan.

Objectives: Neoadjuvant chemoradiotherapy (NCRT) followed by surgery is the mainstay of treatment for patients with locally advanced rectal cancer. Based on baseline 18F-fluorodeoxyglucose ([18F]-FDG)-positron emission tomography (PET)/computed tomography (CT), a new artificial intelligence model using metric learning (ML) was introduced to predict responses to NCRT.

Patients And Methods: This study used the data of 236 patients with newly diagnosed rectal cancer; the data of 202 and 34 patients were for training and validation, respectively. All patients received pretreatment [18F]FDG-PET/CT, NCRT, and surgery. The treatment response was scored by Dworak tumor regression grade (TRG); TRG3 and TRG4 indicated favorable responses. The model employed ML combined with the Uniform Manifold Approximation and Projection for dimensionality reduction. A receiver operating characteristic (ROC) curve analysis was performed to assess the model's predictive performance.

Results: In the training cohort, 115 patients (57%) achieved TRG3 or TRG4 responses. The area under the ROC curve was 0.96 for the prediction of a favorable response. The sensitivity, specificity, and accuracy were 98.3%, 96.5%, and 97.5%, respectively. The sensitivity, specificity, and accuracy for the validation cohort were 95.0%, 100%, and 98.8%, respectively.

Conclusions: The new ML model presented herein was used to determined that baseline 18F[FDG]-PET/CT images could predict a favorable response to NCRT in patients with rectal cancer. External validation is required to verify the model's predictive value.
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http://dx.doi.org/10.3390/cancers13246350DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8699508PMC
December 2021

Primary cutaneous gamma/delta T-cell lymphoma in Taiwan: A series of six cases with frequent solitary presentation and relatively indolent behavior.

J Cutan Pathol 2021 Nov 14. Epub 2021 Nov 14.

Department of Pathology, Chi-Mei Medical Center, Tainan, Taiwan.

Background: Primary cutaneous gamma/delta T-cell lymphoma (PCDG-TCL) is aggressive, frequently presenting as multiple plaques, tumors, and/or subcutaneous nodules.

Methods: In this study, we conducted a retrospective study in a tertiary center in Taiwan to characterize this rare tumor.

Results: We identified six patients. Five presented with a solitary lesion, including two with clinical impression of epidermal inclusion cyst or lipoma. Two of four evaluable cases exhibited epidermotropism, with one mimicking Pautrier microabscess. The neoplastic cells were pleomorphic and mostly medium- to large-sized. In all cases, the neoplastic cells expressed T-cell receptor (TCR)-γ and/or TCR-δ, with four co-expressing βF1. Two of these βF1+ cases co-expressed TCR-γ but not TCR-δ (two different clones). All were negative for Epstein-Barr virus (EBV), low stage, and treated with radiotherapy alone or combined chemotherapy and radiotherapy. In two patients, lymphoma relapsed in 3 and 7 months, respectively, and one patient died of the disease in 7 months. Four other patients were free of disease for 6 to 126 months.

Conclusion: PCGD-TCL cases in Taiwan are more commonly solitary, frequently with indolent courses. The two currently available TCR-δ clones alone might be insufficient to detect all tumors.
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http://dx.doi.org/10.1111/cup.14169DOI Listing
November 2021

Analysis of the pan-Asian subgroup of patients in the NALA Trial: a randomized phase III NALA Trial comparing neratinib+capecitabine (N+C) vs lapatinib+capecitabine (L+C) in patients with HER2+metastatic breast cancer (mBC) previously treated with two or more HER2-directed regimens.

Breast Cancer Res Treat 2021 Oct 23;189(3):665-676. Epub 2021 Sep 23.

Division of Breast Oncology and Surgery, Kaohsiung Medical University Chung-Ho Memorial Hospital, No.100, Tzyou 1st Road, Kaohsiung, 807, Taiwan.

Purpose: Neratinib, an irreversible pan-HER tyrosine kinase inhibitor, has demonstrated systemic efficacy and intracranial activity in various stages of HER2+breast cancer. NALA was a phase III randomized trial that assessed the efficacy and safety of neratinib+capecitabine (N+C) against lapatinib+capecitabine (L+C) in HER2+ metastatic breast cancer (mBC) patients who had received ≥ 2 HER2-directed regimens. Descriptive analysis results of the Asian subgroup in the NALA study are reported herein.

Methods: 621 centrally assessed HER2+ mBC patients were enrolled, 202 of whom were Asian. Those with stable, asymptomatic brain metastases (BM) were eligible for study entry. Patients were randomized 1:1 to N (240 mg qd) + C (750 mg/m bid, day 1-14) with loperamide prophylaxis or to L (1250 mg qd) + C (1000 mg/m bid, day 1-14) in 21-day cycles. Co-primary endpoints were centrally assessed progression-free survival (PFS) and overall survival (OS). Secondary endpoints included time to intervention for central nervous system (CNS) disease, objective response rate, duration of response (DoR), clinical benefit rate, and safety.

Results: 104 and 98 Asian patients were randomly assigned to receive N+C or L+C, respectively. Median PFS of N+C and L+C was 7.0 and 5.4 months (P = 0.0011), respectively. Overall cumulative incidence of intervention for CNS disease was lower with N+C (27.9 versus 33.8%; P = 0.039). Both median OS (23.8 versus 18.7 months; P = 0.185) and DoR (11.1 versus 4.2 months; P < 0.0001) were extended with N+C, compared to L+C. The incidences of grade 3/4 treatment emergent adverse events (TEAEs) and TEAEs leading to treatment discontinuation were mostly comparable between the two arms. Diarrhea and palmar-plantar erythrodysesthesia were the most frequent TEAEs in both arms, similar to the overall population in incidence and severity.

Conclusion: Consistent with the efficacy profile observed in the overall study population, Asian patients with HER2+ mBC, who had received ≥ 2 HER2-directed regimens, may also benefit from N+C. No new safety signals were noted.

Clinical Trial Registration: NCT01808573.
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http://dx.doi.org/10.1007/s10549-021-06313-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8505315PMC
October 2021

Age as a modifier of the effects of chemoradiotherapy with infusional 5-fluorouracil after D2 dissection in gastric cancer.

Aging (Albany NY) 2021 07 5;13(13):17337-17348. Epub 2021 Jul 5.

Department of Environmental and Occupational Health, National Cheng Kung University, Tainan, Taiwan.

Adjuvant concurrent chemoradiotherapy (CCRT) is the standard care for patients with resected advanced gastric cancer, but its survival benefits remain undetermined in patients undergoing D2 lymph node dissection (D2 dissection). We evaluated safety and efficacy of adjuvant CCRT with 5-fluorouracil (5-FU) versus chemotherapy alone in 110 gastric cancer patients with D2 dissection treated in Taiwan between January 2009 and January 2013. All the 71 patients receiving adjuvant CCRT were treated with daily infusional 5-FU and radiotherapy. Adjuvant CCRT was associated with higher risks of major hematologic (56.3% vs. 23.8%, = 0.002) and gastrointestinal (46.9% vs. 14.3%, = 0.027) toxicities and death (12.5% vs. 0.0%, = 0.041) in patients above 70 years old, but this was not the case in those ≤70 years of age. Univariate Cox proportional regressions identified adjuvant CCRT as a factor for better overall survival (OS) (hazard ratio [HR]=0.52; 95% confidence interval [CI]: 0.27-0.99) and disease-free survival (DFS) (HR=0.46, 95% CI: 0.24-0.88), but it was not a significant factor for OS or DFS after adjusting for other factors in the multivariate analysis. However, in stratified analyses by age, we found adjuvant CCRT was an independent prognostic factor for better OS (HR=0.07; 95% CI: 0.01-0.38) in patients ≤70 years old, but not in those above 70 years of age. Therefore, it was concluded that age may to be a modifier of the effects of adjuvant CCRT.
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http://dx.doi.org/10.18632/aging.203223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8312439PMC
July 2021

Etanercept Ameliorates Cardiac Fibrosis in Rats with Diet-Induced Obesity.

Pharmaceuticals (Basel) 2021 Apr 1;14(4). Epub 2021 Apr 1.

Division of Cardiology, Chi-Mei Medical Center Liouying, Tainan City 736, Taiwan.

Diet-induced obesity (DIO) is considered the main risk factor for cardiovascular diseases. Increases in the plasma levels of tumor necrosis factor alpha (TNF-α) is associated with DIO. Etanercept, a TNF-α inhibitor, has been shown to alleviate cardiac hypertrophy. To investigate the effect of etanercept on cardiac fibrosis in DIO model, rats on high fat diet (HFD) were subdivided into two groups: the etanercept group and vehicle group. Cardiac injury was identified by classic methods, while fibrosis was characterized by histological analysis of the hearts. Etanercept treatment at 0.8 mg/kg/week twice weekly by subcutaneous injection effectively alleviates the cardiac fibrosis in HFD-fed rats. STAT3 activation seems to be induced in parallel with fibrosis-related gene expression in the hearts of HFD-fed rats. Decreased STAT3 activation plays a role in the etanercept-treated animals. Moreover, fibrosis-related genes are activated by palmitate in parallel with STAT3 activation in H9c2 cells. Etanercept may inhibit the effects of palmitate, but it is less effective than a direct inhibitor of STAT3. Direct inhibition of STAT3 activation by etanercept seems unlikely. Etanercept has the ability to ameliorate cardiac fibrosis through reduction of STAT3 activation after the inhibition of TNF-α and/or its receptor.
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http://dx.doi.org/10.3390/ph14040320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067047PMC
April 2021

Stereotactic body radiotherapy for pelvic boost in gynecological cancer patients with local recurrence or unsuitable for intracavitary brachytherapy.

Taiwan J Obstet Gynecol 2021 Jan;60(1):111-118

Department of Radiation Oncology, China Medical University Hospital, Taichung, Taiwan; Graduate Institute of Clinical Medical Science, School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan; Department of Radiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. Electronic address:

Objective: To evaluate efficacy of stereotactic body radiotherapy (SBRT) for pelvic boost irradiation in gynecological cancer patients with pelvic recurrence or with intact uterus unsuitable for brachytherapy.

Materials And Methods: We retrospectively reviewed the medical records of 25 gynecological cancer patients who received SBRT boost for pelvic recurrence (salvage group, n = 14), or for local dose escalation instead of intracavitary brachytherapy due to unfavorable medical condition (definitive group, n = 11). The pelvis was irradiated with a median dose of 54 Gy in six weeks, and then SBRT was prescribed with a range of 10-25Gy in two to five fractions. The cumulative radiobiological equivalent dose in 2-Gy fractions (EQD2) to the tumors ranged from 62.5 to 89.5 Gy (median, 80.7). Overall survival (OS) and in-field relapse-free survival (IFRFS) were calculated using the Kaplan-Meier method.

Results: At the initial assessment, eighteen (72%) patients achieved complete or partial remission, and seven (28%) had stable or progressive disease. With a median follow duration of 12 months, the 1-year IFRFS for salvage and definitive group were 64.5% and 90.0%, whereas the 1-year OS for the two groups were 80.8% and 49.1%, respectively. One patient developed entero-vaginal fistula and one had sigmoid perforation. No patient experienced ≧ grade 3 genitourinary complications.

Conclusion: In gynecological cancer patients with recurrent pelvic tumors or intact uterus unsuitable for brachytherapy, local dose escalation with SBRT resulted in an initial response rate of 72% with acceptable early toxicities. A long-term follow-up is required to assess the impact on local control or survival.
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http://dx.doi.org/10.1016/j.tjog.2020.11.017DOI Listing
January 2021

Radiotherapy combined with chemotherapy increases the risk of herpes zoster in patients with gynecological cancers: a nationwide cohort study.

J Gynecol Oncol 2021 03 2;32(2):e13. Epub 2020 Dec 2.

Preventive Medicine Center, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung, Taiwan.

Objective: This study aimed to determine the effect of radiotherapy (RT) on the risk of herpes zoster (HZ) in patients with gynecological cancers via a nationwide population-based study.

Methods: Based on patient data obtained from the National Health Insurance Research Database, 1928 gynecological cancer patients were identified with 1:1 matching for RT and non-RT cohorts by age, index date, and cancer type. Another cohort consisting of 964 non-cancer individuals matched was used as normal control. The incidence of HZ was compared between cancer patients with and without RT. Age, comorbidities, cancer-related surgery and chemotherapy (CT), and cancer type were adjusted as confounders.

Results: The risk of HZ in cancer patients was higher than that of non-cancer individuals (14.23 versus 8.34 per 1,000 person-years [PY], the adjusted hazard ratio [aHR]=1.38, p=0.044). In the cancer population, the incidence of HZ for the RT and non-RT cohorts was 20.55 versus 10.23 per 1,000 PY, respectively (aHR=1.68, p=0.009). Age >50 years was an independent factor for developing HZ. The 5-year actuarial incidence for patients receiving neither RT nor CT, RT alone, CT alone, and combined modalities was 5.4%, 6.9%, 3.7%, and 9.9%, respectively (p<0.001). In the RT cohort, the risk rose rapidly in the first year, becoming steady thereafter.

Conclusion: This population-based study showed that gynecological cancer patients receiving RT combined with CT had the highest cumulative risk of HZ. Health care professionals should be aware of the potential toxicities.
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http://dx.doi.org/10.3802/jgo.2021.32.e13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930445PMC
March 2021

Pretreatment Neutrophil-to-Lymphocyte Ratio Predicts Survival and Liver Toxicity in Patients With Hepatocellular Carcinoma Treated With Stereotactic Ablative Radiation Therapy.

Int J Radiat Oncol Biol Phys 2021 02 6;109(2):474-484. Epub 2020 Sep 6.

Department of Radiation Oncology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan. Electronic address:

Purpose: The objective of this study was to determine whether pretreatment neutrophil-to-lymphocyte ratio (NLR) could predict survival outcomes and liver toxicity in hepatocellular carcinoma (HCC) patients treated with stereotactic ablative radiation therapy (SABR).

Methods And Materials: In this retrospective study we collected pretreatment NLR of HCC patients treated with SABR between December 2007 and August 2018 and determined its association with overall survival (OS), progression-free survival, and radiation-related liver toxicity defined as an increase in the Child-Turcotte-Pugh score by ≥2 within 3 months after SABR in the absence of disease progression.

Results: A total of 153 patients with a median follow-up of 13.3 months were included. Receiver operating characteristic curve analysis found that an NLR ≥2.4 was optimum (area under the curve, 0.762; 95% confidence interval [CI], 0.682-0.841, P < .001) for predicting poor 1-year OS (38.2% vs 83.6%, P < .001). Multivariable analysis demonstrated that NLR was significantly associated with OS, both as a continuous (P = .006) and a binary variable (NLR set at 2.4; P = .003). Multiple tumors (P = .003), macrovascular invasion (P = .024), extrahepatic spread (P = .002), and albumin-bilirubin score (P = .020) were also significant predictors of OS. Elevated NLR independently prognosticated poor progression-free survival (P = .016). Liver toxicity was seen in 22 evaluable patients (15.4%). Receiver operating characteristic curve analysis found NLR ≥4.0 was optimum at predicting liver toxicity (31.4% vs 10.2%, P = .005). A higher NLR (P = .049) and albumin-bilirubin score (P = .002) were independent risk factors for liver toxicity.

Conclusions: NLR is an objective and ubiquitous inflammatory marker that can predict OS and liver toxicity in HCC patients undergoing SABR. NLR could be a useful biomarker for patient risk stratification and therapeutic decision-making.
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http://dx.doi.org/10.1016/j.ijrobp.2020.09.001DOI Listing
February 2021

Aberrant TTF-1 Expression in Peripheral T-Cell Lymphomas: A Diagnostic Pitfall.

Int J Surg Pathol 2021 Apr 10;29(2):165-168. Epub 2020 Aug 10.

38018Chi-Mei Medical Center, Tainan.

Background: Thyroid transcription factor-1 (TTF-1) is a useful marker for identifying thyroid and lung cancers in diagnostic pathology, particularly for the investigation of unknown primary cancers. However, some other tumors such as colorectal cancer might aberrantly express TTF-1, particularly with the less specific clone SPT24. Occasional diffuse large B-cell lymphoma (DLBCL) cases have been reported to be TTF-1-positive, yet there is no information on TTF-1 expression in peripheral T-cell lymphoma (PTCL).

Methods: We investigated a series of PTCL and DLBCL by immunohistochemistry for TTF-1 expression using 2 commercially available clones.

Results: We found that 33% (5/15) adult T-cell leukemia/lymphomas (ATLLs) and 25% (2/8) angioimmunoblastic T-cell lymphomas (AITLs) were positive by clone SPT24 and only 2ATLL cases were positive by clone 8G7G3/1. Overall TTF-1 expression rates of PTCL by SPT24 and 8G7G3/1 were 16% (7/43) and 5% (2/43), respectively. All DLBCLs were negative.

Conclusion: Although TTF-1 is a relatively specific marker for thyroid and lung cancers, it might be expressed in some lymphomas, particularly PTCL when using clone SPT24. Pathologist should be aware of this possible diagnostic pitfall when using TTF-1 in investigating tumors of unknown origin.
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http://dx.doi.org/10.1177/1066896920946835DOI Listing
April 2021

Neratinib Plus Capecitabine Versus Lapatinib Plus Capecitabine in HER2-Positive Metastatic Breast Cancer Previously Treated With ≥ 2 HER2-Directed Regimens: Phase III NALA Trial.

J Clin Oncol 2020 09 17;38(27):3138-3149. Epub 2020 Jul 17.

Graduate School of Medicine, Gunma University, Gunma, Japan.

Purpose: NALA (ClinicalTrials.gov identifier: NCT01808573) is a randomized, active-controlled, phase III trial comparing neratinib, an irreversible pan-HER tyrosine kinase inhibitor (TKI), plus capecitabine (N+C) against lapatinib, a reversible dual TKI, plus capecitabine (L+C) in patients with centrally confirmed HER2-positive, metastatic breast cancer (MBC) with ≥ 2 previous HER2-directed MBC regimens.

Methods: Patients, including those with stable, asymptomatic CNS disease, were randomly assigned 1:1 to neratinib (240 mg once every day) plus capecitabine (750 mg/m twice a day 14 d/21 d) with loperamide prophylaxis, or to lapatinib (1,250 mg once every day) plus capecitabine (1,000 mg/m twice a day 14 d/21 d). Coprimary end points were centrally confirmed progression-free survival (PFS) and overall survival (OS). NALA was considered positive if either primary end point was met (α split between end points). Secondary end points were time to CNS disease intervention, investigator-assessed PFS, objective response rate (ORR), duration of response (DoR), clinical benefit rate, safety, and health-related quality of life (HRQoL).

Results: A total of 621 patients from 28 countries were randomly assigned (N+C, n = 307; L+C, n = 314). Centrally reviewed PFS was improved with N+C (hazard ratio [HR], 0.76; 95% CI, 0.63 to 0.93; stratified log-rank 0059). The OS HR was 0.88 (95% CI, 0.72 to 1.07; 2098). Fewer interventions for CNS disease occurred with N+C versus L+C (cumulative incidence, 22.8% 29.2%; 043). ORRs were N+C 32.8% (95% CI, 27.1 to 38.9) and L+C 26.7% (95% CI, 21.5 to 32.4; 1201); median DoR was 8.5 versus 5.6 months, respectively (HR, 0.50; 95% CI, 0.33 to 0.74; .0004). The most common all-grade adverse events were diarrhea (N+C 83% L+C 66%) and nausea (53% 42%). Discontinuation rates and HRQoL were similar between groups.

Conclusion: N+C significantly improved PFS and time to intervention for CNS disease versus L+C. No new N+C safety signals were observed.
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http://dx.doi.org/10.1200/JCO.20.00147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7499616PMC
September 2020

Genomic Biomarkers of Survival in Patients with Adenocarcinoma of the Uterine Cervix Receiving Chemoradiotherapy.

Int J Mol Sci 2020 Jun 9;21(11). Epub 2020 Jun 9.

Center for Precision Medicine, China Medical University Hospital, Taichung 404, Taiwan.

This study investigated the prognostic effects of genomic biomarkers for predicting chemoradiotherapy (CRT)-based treatment outcomes in patients with adenocarcinoma (AC) of the uterine cervix. In all, 21 patients receiving definitive CRT were included. In accordance with the International Federation of Gynecology and Obstetrics (FIGO) staging system, 5, 8, and 8 patients were classified as having stage IB3, II, and III disease, respectively. Pretreatment biomarkers were analyzed using tissue microarrays from biopsy specimens. Genomic alterations were examined by next-generation sequencing (NGS). The outcome endpoints were disease-free survival (DFS), distant metastasis-free survival (DMFS), and local relapse-free survival (LRFS). A Cox regression model was used to examine the prognostic effects of the biomarkers and clinical parameters. The presence of myeloid cell leukemia-1 () gene amplification and a lower immunohistochemical (IHC) marker of tumor necrotic factor alpha (TNF-α) H-score were two prognostic factors for inferior DFS. The four-year DFS was 28% and 68% for patients with or without MCL1 copy number gain, respectively ( = 0.028). In addition, MCL1 amplification predicted poor DMFS. A lower tumor mutation number (TMN) calculated from nonsynonymous mutations was associated with lower LRFS. For patients with adenocarcinoma of the uterine cervix receiving definitive CRT, prognostic information can be supplemented by amplification, the TMN, and the TNF-α H score.
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http://dx.doi.org/10.3390/ijms21114117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7312424PMC
June 2020

Predicting pathological complete response in rectal cancer after chemoradiotherapy with a random forest using F-fluorodeoxyglucose positron emission tomography and computed tomography radiomics.

Ann Transl Med 2020 Mar;8(5):207

Center of Augmented Intelligence in Healthcare, China Medical University Hospital, Taichung.

Background: Neoadjuvant chemoradiotherapy (NCRT) followed by surgery is the standard treatment for patients with locally advanced rectal cancer. This study developed a random forest (RF) model to predict pathological complete response (pCR) based on radiomics derived from baseline F-fluorodeoxyglucose ([F]FDG)-positron emission tomography (PET)/computed tomography (CT).

Methods: This study included 169 patients with newly diagnosed rectal cancer. All patients received F[FDG]-PET/CT, NCRT, and surgery. In total, 68 radiomic features were extracted from the metabolic tumor volume. The numbers of splits in a decision tree and trees in an RF were determined based on their effects on predictive performance. Receiver operating characteristic curve analysis was performed to evaluate predictive performance and ascertain the optimal threshold for maximizing prediction accuracy.

Results: After NCRT, 22 patients (13%) achieved pCR, and 42 features that could differentiate tumors with pCR were used to construct the RF model. Six decision trees and seven splits were suitable. Accordingly, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 81.8%, 97.3%, 81.8%, 97.3%, and 95.3%, respectively.

Conclusions: By using an RF, we determined that radiomics derived from baseline F[FDG]-PET/CT could accurately predict pCR in patients with rectal cancer. Highly accurate and predictive values can be achieved but should be externally validated.
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http://dx.doi.org/10.21037/atm.2020.01.107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7154452PMC
March 2020

Effectiveness of stereotactic ablative radiotherapy in patients with advanced hepatocellular carcinoma unsuitable for transarterial chemoembolization.

Ther Adv Med Oncol 2019 4;11:1758835919889002. Epub 2019 Dec 4.

Taipei Cancer Center, Taipei Medical University, No.250, Wu Hsing Street, Xinyi District, 110, Taipei City.

Background: Stereotactic ablative radiotherapy (SABR) can deliver tumoricidal doses and achieve long-term control in early hepatocellular carcinoma (HCC). However, limited studies have investigated the safety and effectiveness of SABR in patients with advanced diseases that is unsuitable for transarterial chemoembolization (TACE).

Methods: In this observational study, we reviewed the medical records of patients with Barcelona Clinic Liver Cancer (BCLC) stage C disease treated with linear accelerator-based SABR between 2008 and 2016. Their tumors were either refractory to TACE or TACE was contraindicated. Overall survival (OS), in-field progression-free survival (IFPFS), and out-field progression-free survival were calculated using Kaplan-Meier analysis. The Cox regression model was used to examine the effects of variables. Treatment-related toxicities were scored according to the Common Terminology Criteria for Adverse Events (version 4.03) and whether patients developed radiation-induced liver disease (RILD) after SABR.

Results: This study included 32 patients. The mean maximal tumor diameter and tumor volumes were 4.7 cm and 135.9 ml, respectively. Patients received linear accelerator-based SABR with a median prescribed dose of 48 Gy (30-60 Gy) in three to six fractions. Based on the assessment of treatment response by using the Response Evaluation Criteria in Solid Tumors (version 1.1), 19% of patients achieved a complete response and 53% achieved a partial response. After a median follow-up of 18.1 months (4.0-65.9 months), 10, 19, and 9 patients experienced in-field failure, out-field hepatic recurrence, and extrahepatic metastases, respectively. The estimated 2-year OS and IFPFS rates were 54.4% and 62.7%, respectively. In a multivariate analysis, a pretreatment Cancer of the Liver Italian Program (CLIP) score of ⩾2 ( = 0.01) was a prognostic factor for shorter OS, and a biologically effective dose (BED) of < 85 Gy ( = 0.011) and a Child-Pugh score of ⩾6 ( = 0.014) were prognostic factors for inferior IFPFS. In this study five and eight patients developed classic and nonclassic RILD, respectively.

Conclusions: SABR can serve as a salvage treatment for patients with HCC with BCLC stage C disease unsuitable for TACE, in particular, in those with a baseline CLIP score of ⩽1. A BED of ⩾85 Gy is an appropriate prescribed dose for tumor control. Because out-field relapse is the major cause of treatment failure, SABR in combination with novel systemic modalities should be investigated in future studies.
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http://dx.doi.org/10.1177/1758835919889002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6893933PMC
December 2019

Immunohistochemical Biomarkers of Survival in Patients With Adenocarcinoma of the Uterine Cervix Receiving Chemoradiotherapy.

Anticancer Res 2019 Jun;39(6):3231-3240

Department of Radiation Oncology, China Medical University Hospital, Taichung, Taiwan, R.O.C.

Background/aim: To determine the prognostic effects of immunohistochemical biomarkers for predicting chemoradiotherapy (CRT)-based treatment outcomes in patients with adenocarcinoma of the uterine cervix.

Materials And Methods: This study included 42 patients receiving definitive CRT. According to the International Federation of Gynecology and Obstetrics staging system, 13, 21, and 8 patients were classified as having stage IB2, II, and III disease, respectively. Baseline immunohistochemical biomarkers, including those for hypoxia, cell proliferation, cell adhesion, immunogenicity, and evasion of apoptosis, were analyzed using tissue microarrays from biopsy specimens.

Results: Myeloid cell leukemia-1 (MCL1) overexpression and the presence of pelvic lymph node metastasis were two prognostic factors for inferior cancer-specific survival. A higher H-score for c-MYC proto-oncogene, bHLH transcription factor (c-MYC) was associated with lower pelvic relapse-free survival.

Conclusion: For patients with adenocarcinoma of the uterine cervix requiring definitive CRT, treatment outcomes can be stratified by the immunohistochemical biomarkers MCL1 and c-MYC for cancer death and local failure, respectively.
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http://dx.doi.org/10.21873/anticanres.13464DOI Listing
June 2019

Effectiveness of Image-guided Brachytherapy in Patients With Locally Advanced Cervical Squamous Cell Carcinoma Receiving Concurrent Chemoradiotherapy.

Anticancer Res 2019 Jun;39(6):3015-3024

Department of Obstetrics and Gynecology, China Medical University Hospital, Taichung, Taiwan, R.O.C.

Aim: To compare the advantage of image-guided brachytherapy (IGBT) over conventional two-dimensional brachytherapy (2DBT) in patients with advanced cervical squamous cell carcinoma.

Patients And Methods: This study included 253 patients with stage IB2-IVA diseases treated with two schemes of brachytherapy. One hundred and thirty-six patients received 2DBT, whereas 117 patients received IGBT. Tumor stage, age, and tumor diameter were matched between the two groups. Local relapse-free survival, overall survival, and cumulative incidences of gastrointestinal and genitourinary complications were compared between the two groups.

Results: The overall and local relapse-free survival rates were similar between the two groups. The cumulative rate of grade 2 and higher gastrointestinal complication was 21.3% for the 2DBT group, and 8.5% for the IGBT group (p=0.007), whereas that of grade 2 and higher genitourinary injury was 11.8% for the 2DBT group, and 1.7% for the IGBT group (p=0.002).

Conclusion: In patients with advanced cervical squamous cell carcinoma, IGBT achieves a higher therapeutic ratio compared to 2DBT technique by minimizing the late toxicities.
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http://dx.doi.org/10.21873/anticanres.13434DOI Listing
June 2019

Prediction of local relapse and distant metastasis in patients with definitive chemoradiotherapy-treated cervical cancer by deep learning from [F]-fluorodeoxyglucose positron emission tomography/computed tomography.

Eur Radiol 2019 Dec 27;29(12):6741-6749. Epub 2019 May 27.

Department of Nuclear Medicine and PET Center, China Medical University Hospital, Taichung, Taiwan.

Background: We designed a deep learning model for assessing F-FDG PET/CT for early prediction of local and distant failures for patients with locally advanced cervical cancer.

Methods: All 142 patients with cervical cancer underwent F-FDG PET/CT for pretreatment staging and received allocated treatment. To augment the amount of image data, each tumor was represented as 11 slice sets each of which contains 3 2D orthogonal slices to acquire a total of 1562 slice sets. In each round of k-fold cross-validation, a well-trained proposed model and a slice-based optimal threshold were derived from a training set and used to classify each slice set in the test set into the categories of with or without local or distant failure. The classification results of each tumor were aggregated to summarize a tumor-based prediction result.

Results: In total, 21 and 26 patients experienced local and distant failures, respectively. Regarding local recurrence, the tumor-based prediction result summarized from all test sets demonstrated that the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 71%, 93%, 63%, 95%, and 89%, respectively. The corresponding values for distant metastasis were 77%, 90%, 63%, 95%, and 87%, respectively.

Conclusion: This is the first study to use deep learning model for assessing F-FDG PET/CT images which is capable of predicting treatment outcomes in cervical cancer patients.

Key Points: • This is the first study to use deep learning model for assessing F-FDG PET/CT images which is capable of predicting treatment outcomes in cervical cancer patients. • All 142 patients with cervical cancer underwent F-FDG PET/CT for pretreatment staging and received allocated treatment. To augment the amount of image data, each tumor was represented as 11 slice sets each of which contains 3 2D orthogonal slices to acquire a total of 1562 slice sets. • For local recurrence, all test sets demonstrated that the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 71%, 93%, 63%, 95%, and 89%, respectively. The corresponding values for distant metastasis were 77%, 90%, 63%, 95%, and 87%, respectively.
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http://dx.doi.org/10.1007/s00330-019-06265-xDOI Listing
December 2019

Impact of body-mass factors on setup displacement during pelvic irradiation in patients with lower abdominal cancer.

Radiol Oncol 2019 04 5;53(2):256-264. Epub 2019 Apr 5.

Department of Radiation Oncology, China Medical University Hospital, Taichung, Taiwan.

Background The aim of the study was investigate the impact of body-mass factors (BMF) on setup displacement during pelvic radiotherapy in patients with lower abdominal cancers. Patients and methods The clinical data of a training cohort composed of 60 patients with gynecological, rectal, or prostate cancer were analyzed. The daily alignment data from image-guided radiotherapy (IGRT) were retrieved. Setup errors for were assessed by systematic error (SE) and random error (RE) through the superior-inferior (SI), anterior-posterior (AP), and medial-lateral (ML) directions. Several BMFs and patient-related parameters were analyzed with binary logistic regression and receiver-operating characteristic curves. A scoring system was proposed to identify those with greater setup displacement during daily treatment. The results were validated by another cohort. Results A large hip lateral diameter correlated with a greater SI-SE and AP-SE, whereas a large umbilical AP diameter correlated with a greater ML-SE and ML-RE. A higher SI-RE was associated with a large hip circumference. The positive predictors for setup uncertainty were chosen to dichotomize patients into groups at high risk and low risk for setup displacement. Based on the scoring system, the adequate treatment margins for the SI direction in the high-and low-risk groups were 5.4 mm and 3.8 mm, whereas those for the ML direction were 8.2 mm and 4.2 mm, respectively. The validated cohort showed a similar trend. Conclusions Large BMFs including hip lateral diameter, hip circumference, and umbilical AP diameter are associated with greater setup uncertainty. Based on the scores, IGRT or required treatment margins can be adapted for patients with high risk features.
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http://dx.doi.org/10.2478/raon-2019-0017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6572488PMC
April 2019

Textural features of cervical cancers on FDG-PET/CT associate with survival and local relapse in patients treated with definitive chemoradiotherapy.

Sci Rep 2018 08 8;8(1):11859. Epub 2018 Aug 8.

Department of Nuclear Medicine and PET Center, China Medical University Hospital, Taichung, Taiwan.

We retrospectively reviewed the records of 142 patients with stage IB-IIIB cervical cancer who underwent F-FDG-PET/CT before external beam radiotherapy plus intracavitary brachytherapy and concurrent chemotherapy. The patients were divided into training and validation cohorts to confirm the reliability of predictors for recurrence. Kaplan-Meier analysis was performed and a Cox regression model was used to examine the effects of variables on overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and pelvic relapse-free survival (PRFS). High gray-level run emphasis (HGRE) derived from gray-level run-length matrix most accurately and consistently predicted the presence of pelvic residual or recurrent tumors for both cohorts. In multivariate analysis, stages IIIA-IIIB (P = 0.001, hazard ratio [HR] = 4.07) and a low HGRE (P < 0.0001, HR = 4.34) were prognostic factors for low OS, whereas a low HGRE (P = 0.001, HR = 2.86) and nonsquamous cell histology (P = 0.003, HR = 2.76) were prognostic factors for inferior PFS. The nonsquamous cell histology (P < 0.0001, HR = 9.19) and a low HGRE (P = 0.001, HR = 4.69) were predictors for low PRFS. In cervical cancer patients receiving definitive chemoradiotherapy, pretreatment textural features on F-FDG-PET/CT can supplement the prognostic information.
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http://dx.doi.org/10.1038/s41598-018-30336-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6082904PMC
August 2018

Metabolic Imaging Phenotype Using Radiomics of [F]FDG PET/CT Associated with Genetic Alterations of Colorectal Cancer.

Mol Imaging Biol 2019 02;21(1):183-190

Graduate Institute of Clinical Medical Science, School of Medicine, College of Medicine, China Medical University, No. 2, Yuh-Der Road, Taichung, 404, Taiwan.

Purpose: To understand the association between genetic mutations and radiomics of 2-deoxy-2-[F]fluoro-D-glucose ([F]FDG) positron emission tomography (PET)/x-ray computed tomography (CT) in patients with colorectal cancer (CRC).

Procedures: This study included 74 CRC patients who had undergone preoperative [F]FDG PET/CT. A total of 65 PET/CT-related features including intensity, volume-based, histogram, and textural features were calculated. High-resolution melting methods were used for genetic mutation analysis.

Results: Genetic mutants were found in 21 KRAS tumors (28 %), 31 TP53 tumors (42 %), and 17 APC tumors (23 %). Tumors with a mutated KRAS had an increased value at the 25th percentile of maximal standardized uptake value (SUV) within their metabolic tumor volume (MTV) (P < .0001; odds ratio [OR] 1.99; 95 % confidence interval [CI] 1.37-2.90) and their contrast from the gray-level cooccurrence matrix (P = .005; OR 1.52; 95 % CI 1.14-2.04). A mutated TP53 was associated with an increased value of short-run low gray-level emphasis derived from the gray-level run length matrix (P = .001; OR 243006.0; 95 % CI 59.2-996,872,313). APC mutants exhibited lower low gray-level zone emphasis derived from the gray-level zone length matrix (P = .006; OR < .0001; 95 % CI 0.000-0.22).

Conclusion: PET/CT-derived radiomics can provide supplemental information to determine KRAS, TP53, and APC genetic alterations in CRC.
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http://dx.doi.org/10.1007/s11307-018-1225-8DOI Listing
February 2019

Effects of a Psychoeducational Intervention in Patients With Breast Cancer Undergoing Chemotherapy.

J Nurs Res 2018 Aug;26(4):266-279

MSN, RN, Senior Administrator, Cancer Center, Chi Mei Medical Center, Liouying.

Background: Compelling evidence has yet to be published regarding the positive effect of psychoeducational interventions (PEIs) on psychological distress in patients with breast cancer. The impact of PEIs on self-efficacy, resilience, and quality of life is also unclear.

Purpose: The aim of this study was to assess the effects of a PEI on anxiety, depression, disease-specific care knowledge, self-efficacy, resilience and quality of life in patients with breast cancer during and after chemotherapy. The intervention was administered before and during five rounds of chemotherapy treatment.

Methods: A randomized controlled trial was conducted. Patients with breast cancer (N = 40) were randomly assigned to either the experimental or control group. The experimental group participated in PEI, a brief and highly structured program consisting of two parts: (a) an educational manual that addressed depression, anxiety, disease-specific care knowledge, self-efficacy, and resilience and (b) a self-assessment of learning. The control group received only traditional pamphlet education. Data were collected at four time points: before the first chemotherapy session (T1), during the third chemotherapy session (T2), during the fifth chemotherapy session (T3), and at 2 weeks after the final chemotherapy session (T4).

Results: Anxiety, depression, resilience, and quality of life in the experimental group showed significant differences at T4. Significant differences became apparent at T2 for knowledge and at T3 for self-efficacy. The effects of knowledge, resilience, and quality of life remained significant when group and time interactions were included in the model, showing a positive relationship between PEI and the variables of knowledge, resilience, and quality of life.

Conclusions/implications For Practice: Face-to-face PEI for patients with breast cancer is potentially effective in improving knowledge, resilience, and quality of life during and after chemotherapy. In the current study, PEI significantly improved disease care techniques, reduced chemotherapy-related discomfort, and improved quality of life for participants in the experimental group.
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http://dx.doi.org/10.1097/jnr.0000000000000252DOI Listing
August 2018

Associations of Tumor PD-1 Ligands, Immunohistochemical Studies, and Textural Features in F-FDG PET in Squamous Cell Carcinoma of the Head and Neck.

Sci Rep 2018 01 8;8(1):105. Epub 2018 Jan 8.

Department of Nuclear Medicine and PET Center, China Medical University Hospital, Taichung, Taiwan.

To know tumor PD-L1 expression through IHC or the FDG-PET related radiomics, we investigated the association between programmed cell death protein 1 ligand (PD-L1) expression and immunohistochemical (IHC) biomarkers or textural features of 18F-fluoro-2-deoxdeoxyglucose positron emission tomography (F-FDG PET) in 53 oropharyngeal or hypopharyngeal cancer patients who were ready to undergo radiotherapy-based treatment. Differences in textural features or biomarkers between tumors with and without PD-L1 expression were tested using a Mann-Whitney U test. The predicted values for PD-L1 expression were examined using logistic regression analysis. The mean percentages of tumor PD-L1 expression were 6.2 ± 13.5. Eighteen tumors had PD-L1 expression ≥5%, whereas 30 tumors ≥1%. Using a 5% cutoff, the p16 staining percentage and the textural index of correlation were two factors associated with PD-L1 expression. The odds ratios (ORs) were 17.00 (p = 0.028) and 0.009 (p = 0.015), respectively. When dichotomizing PD-L1 at 1%, the p16 and Ki-67 staining percentages were two predictors for PD-L1 expression with ORs of 11.41 (p = 0.035) and 757.77 (p = 0.045). p16 and Ki-67 staining percentages and several PET/CT-derived textural features can provide supplemental information to determine tumor PD-L1 expression in HNCs.
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http://dx.doi.org/10.1038/s41598-017-18489-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5758832PMC
January 2018

Immunohistochemical biomarkers and volumetric parameters for predicting radiotherapy-based outcomes in patients with p16-negative pharyngeal cancer.

Oncotarget 2017 Sep 21;8(42):72342-72351. Epub 2017 Aug 21.

Graduate Institute of Clinical Medical Science, School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan.

Background: This study determined the prognostic effects of immunohistochemical biomarkers and volumetric parameters predicting radiotherapy-based treatment in patients with p16-negative squamous cell carcinoma of the oropharynx or hypopharynx.

Results: VEGF immunoreactivity > 2 and GLUT1 overexpression were prognostic factors for lower cause-specific survival. Moreover, both factors were associated with lower disease-free survival. The predictors of lower primary relapse-free survival were VEGF immunoreactivity > 2 and CT-based gross tumor volume > 16 mL.

Materials And Methods: Immunohistochemical biomarkers in pretreatment biopsy specimens from 60 patients with p16-negative cancer were analyzed using tissue microarrays. Computed tomography (CT)-based and biological tumor volumes were retrieved through fluorodeoxyglucose positron emission tomography-CT. Correlations of cause-specific, disease-free, and primary relapse-free survival with volumetric parameters and the immunohistochemical biomarker score were investigated.

Conclusions: For patients with p16-negative pharyngeal cancer receiving radiotherapy, treatment outcomes can be stratified by VEGF and GLUT1 expression and CT-based gross tumor volume.
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http://dx.doi.org/10.18632/oncotarget.20374DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5641134PMC
September 2017

[18]Fluorodeoxyglucose Positron Emission Tomography for the Textural Features of Cervical Cancer Associated with Lymph Node Metastasis and Histological Type.

Eur J Nucl Med Mol Imaging 2017 Sep 14;44(10):1721-1731. Epub 2017 Apr 14.

Graduate Institute of Clinical Medical Science, School of Medicine, College of Medicine, China Medical University, No. 2, Yuh-Der Road, Taichung, 40447, Taiwan, Republic of China.

Background: In this study, we investigated the correlation between the lymph node (LN) status or histological types and textural features of cervical cancers on F-fluorodeoxyglucose positron emission tomography/computed tomography.

Methods: We retrospectively reviewed the imaging records of 170 patients with International Federation of Gynecology and Obstetrics stage IB-IVA cervical cancer. Four groups of textural features were studied in addition to the maximum standardized uptake value (SUV), metabolic tumor volume, and total lesion glycolysis (TLG). Moreover, we studied the associations between the indices and clinical parameters, including the LN status, clinical stage, and histology. Receiver operating characteristic curves were constructed to evaluate the optimal predictive performance among the various textural indices. Quantitative differences were determined using the Mann-Whitney U test. Multivariate logistic regression analysis was performed to determine the independent factors, among all the variables, for predicting LN metastasis.

Results: Among all the significant indices related to pelvic LN metastasis, homogeneity derived from the gray-level co-occurrence matrix (GLCM) was the sole independent predictor. By combining SUV, the risk of pelvic LN metastasis can be scored accordingly. The TLG was the independent feature of positive para-aortic LNs. Quantitative differences between squamous and nonsquamous histology can be determined using short-zone emphasis (SZE) from the gray-level size zone matrix (GLSZM).

Conclusion: This study revealed that in patients with cervical cancer, pelvic or para-aortic LN metastases can be predicted by using textural feature of homogeneity from the GLCM and TLG respectively. SZE from the GLSZM is the sole feature associated with quantitative differences between squamous and nonsquamous histology.
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http://dx.doi.org/10.1007/s00259-017-3697-1DOI Listing
September 2017

A topology-based method to mitigate the dosimetric uncertainty caused by the positional variation of the boost volume in breast conservative radiotherapy.

Radiat Oncol 2017 Mar 20;12(1):55. Epub 2017 Mar 20.

Department of Radiation Oncology, China Medical University Hospital, 2nd Yu-De Road, North District, Taichung City, Taiwan.

Background: To improve local control rate in patients with breast cancer receiving adjuvant radiotherapy after breast conservative surgery, additional boost dose to the tumor bed could be delivered simultaneously via the simultaneous integrated boost (SIB) modulated technique. However, the position of tumor bed kept changing during the treatment course as the treatment position was aligned to bony anatomy. This study aimed to analyze the positional uncertainties between bony anatomy and tumor bed, and a topology-based approach was derived to stratify patients with high variation in tumor bed localization.

Methods: Sixty patients with early-stage breast cancer or ductal carcinoma in situ were enrolled. All received adjuvant whole breast radiotherapy with or without local boost via SIB technique. The delineation of tumor bed was defined by incorporating the anatomy of seroma, adjacent surgical clips, and any architectural distortion on computed tomography simulation. A total of 1740 on-board images were retrospectively analyzed. Positional uncertainty of tumor bed was assessed by four components: namely systematic error (SE), and random error (RE), through anterior-posterior (AP), cranial-caudal (CC), left-right (LR) directions and couch rotation (CR). Age, tumor location, and body-mass factors including volume of breast, volume of tumor bed, breast thickness, and body mass index (BMI) were analyzed for their predictive role. The appropriate margin to accommodate the positional uncertainty of the boost volume was assessed, and the new plans with this margin for the tumor bed was designed as the high risk planning target volume (PTV-H) were created retrospectively to evaluate the impact on organs at risk.

Results: In univariate analysis, a larger breast thickness, larger breast volume, higher BMI, and different tumor locations correlated with a greater positional uncertainty of tumor bed. However, BMI was the only factor associated with displacements of surgical clips in the multivariate analysis and patients with higher BMI were stratified as high variation group. When image guidance was aligned to bony structures, the SE and RE of clip displacement were consistently larger in the high variation group. The corresponding PTV-H margins for the high- and low-variation groups were 7, 10, 10 mm and 4, 9, 6 mm in AP, CC, LR directions, respectively. The heart dose between the two plans was not significantly different, whereas the dosimetric parameters for the ipsilateral lung were generally higher in the new plans.

Conclusions: In patients with breast cancer receiving adjuvant radiotherapy, a higher BMI is associated with a greater positional uncertainty of the boost tumor volume. More generous margin should be considered and it can be safely applied through proper design of beam arrangement with advanced treatment techniques.
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http://dx.doi.org/10.1186/s13014-017-0801-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5359879PMC
March 2017

Lymphoma in Taiwan: Review of 1347 neoplasms from a single institution according to the 2016 Revision of the World Health Organization Classification.

J Formos Med Assoc 2017 Aug 18;116(8):620-625. Epub 2016 Dec 18.

Department of Radiology, Chi-Mei Medical Center, Tainan, Taiwan.

Background/purpose: Lymphoid neoplasms are heterogeneous and types of lymphoma vary in different geographic regions. In this study, we aimed at classifying the lymphoid neoplasms at our institution in Taiwan and to compare the relative frequency of various types of lymphoma in different countries.

Methods: We retrospectively searched the files of patients diagnosed with lymphoma at our institution from 2000 to 2015 based on the 2016 Revision of the World Health Organization classification.

Results: We identified 1339 patients with lymphoid neoplasms; among them, eight had two distinct types of lymphoid neoplasms. Of the 1347 neoplasms, 6.09% were Hodgkin lymphomas (HLs) and 93.31%, non-HL (NHLs). Among the 1257 NHLs, 82.66% were of B-cell lineage and 17.34% of T-cell lineage. The most common B-cell lymphoma types were diffuse large B-cell lymphoma, follicular lymphoma, and mucosa-associated lymphoid tissue lymphoma. Among T-cell neoplasms, 37% cases were of nodal origin and 63% cases arose in extranodal sites. The most common nodal and extranodal T-cell neoplasms were angioimmunoblastic T-cell lymphoma and extranodal natural killer/T-cell lymphoma, nasal type, respectively.

Conclusion: We analyzed the largest series of lymphomas to date from Taiwan and concluded that HL was rare and T-cell neoplasms comprised around 17% of all NHLs in Taiwan. The relative frequency of the major lymphoma types is similar in East Asian countries, with only a minor difference, but the overall pattern in the East is quite different from that in the West, with the latter showing a higher frequency of HL and a lower rate of T-cell neoplasms.
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http://dx.doi.org/10.1016/j.jfma.2016.11.006DOI Listing
August 2017

Correlation of pretreatment F-FDG PET tumor textural features with gene expression in pharyngeal cancer and implications for radiotherapy-based treatment outcomes.

Eur J Nucl Med Mol Imaging 2017 Apr 20;44(4):567-580. Epub 2016 Dec 20.

Graduate Institute of Clinical Medical Science, School of Medicine, College of Medicine, China Medical University, No. 2, Yuh-Der Road, Taichung, 40447, Taiwan.

Purpose: This study investigated the correlation of the matrix heterogeneity of tumors on F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) with gene-expression profiling in patients with pharyngeal cancer and determined the prognostic factors for radiotherapy-based treatment outcomes.

Methods: We retrospectively reviewed the records of 57 patients with stage III-IV oropharyngeal or hypopharyngeal cancer who had completed definitive therapy. Four groups of the textural features as well as 31 indices were studied in addition to maximum standard uptake value, metastatic tumor volume, and total lesion glycolysis. Immunohistochemical data from pretreatment biopsy specimens (Glut1, CAIX, VEGF, HIF-1α, EGFR, Ki-67, Bcl-2, CLAUDIN-4, YAP-1, c-Met, and p16) were analyzed. The relationships between the indices and genomic expression were studied, and the robustness of various textural features relative to cause-specific survival and primary relapse-free survival was analyzed.

Results: The overexpression of VEGF was positively associated with the increased values of the matrix heterogeneity obtained using gray-level nonuniformity for zone (GLNUz) and run-length nonuniformity (RLNU). Advanced T stage (p = 0.01, hazard ratio [HR] = 3.38), a VEGF immunoreactive score of >2 (p = 0.03, HR = 2.79), and a higher GLNUz value (p = 0.04, HR = 2.51) were prognostic factors for low cause-specific survival, whereas advanced T stage, a HIF-1α staining percentage of ≥80%, and a higher GLNUz value were prognostic factors for low primary-relapse free survival.

Conclusions: The overexpression of VEGF was associated with the increased matrix index of GLNUz and RLNU. For patients with pharyngeal cancer requiring radiotherapy, the treatment outcome can be stratified according to the textural features, T stage, and biomarkers.
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http://dx.doi.org/10.1007/s00259-016-3580-5DOI Listing
April 2017

Immunohistochemical overexpression of hypoxia-induced factor 1α associated with slow reduction in fluoro-2-deoxy-D-glucose uptake for chemoradiotherapy in patients with pharyngeal cancer.

Eur J Nucl Med Mol Imaging 2016 Dec 16;43(13):2343-2352. Epub 2016 Jun 16.

Department of Nuclear Medicine and PET Center, China Medical University Hospital, Taichung, Taiwan.

Background: This study examined genomic factors associated with a reduction in fluoro-2-deoxy-D-glucose (FDG) uptake during positron emission tomography-computed tomography (PET-CT) for definitive chemoradiotherapy (CRT) in patients with pharyngeal cancer.

Methods: The pretreatment and interim PET-CT images of 25 patients with advanced pharyngeal cancers receiving definitive CRT were prospectively evaluated. The maximum standardized uptake value (SUV) of the interim PET-CT and the reduction ratio of the SUV (SRR) between the two images were measured. Genomic data from pretreatment incisional biopsy specimens (SLC2A1, CAIX, VEGF, HIF1A, BCL2, Claudin-4, YAP1, MET, MKI67, and EGFR) were analyzed using tissue microarrays. Differences in FDG uptake and SRRs between tumors with low and high gene expression were examined using the Mann-Whitney test. Cox regression analysis was performed to examine the effects of variables on local control.

Results: The SRR of the primary tumors (SRR-P) was 0.59 ± 0.31, whereas the SRR of metastatic lymph nodes (SRR-N) was 0.54 ± 0.32. Overexpression of HIF1A was associated with a high iSUV of the primary tumor (P < 0.001) and neck lymph node (P = 0.04) and a low SRR-P (P = 0.02). Multivariate analysis revealed that patients who had tumors with low SRR-P or high HIF1A expression levels showed inferior local control.

Conclusion: In patients with pharyngeal cancer requiring CRT, HIF1A overexpression was positively associated with high interim SUV or a slow reduction in FDG uptake. Prospective trials are needed to determine whether the local control rate can be stratified using the HIF1A level as a biomarker and SRR-P.
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http://dx.doi.org/10.1007/s00259-016-3436-zDOI Listing
December 2016

Immunophenotypic and genetic characteristics of diffuse large B-cell lymphoma in Taiwan.

J Formos Med Assoc 2016 Nov 20;115(11):961-967. Epub 2016 Oct 20.

Department of Pathology, Chi-Mei Medical Center, Tainan, Taiwan; Department of Pathology, Taipei Medical University, Taipei, Taiwan; Department of Pathology, National Taiwan University, Taipei, Taiwan. Electronic address:

Background/purpose: Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma type. The immunophenotypic and genetic features of DLBCL in Taiwan have not been characterized.

Methods: In this study, we performed immunohistochemical analysis and interphase fluorescence in situ hybridization (FISH) using tissue microarray sections to investigate a cohort of unselected DLBCL cases in a single institution in Taiwan from 1990 to 2010.

Results: Of the 153 cases investigated, CD10, bcl-6, and MUM1 were expressed in 16.3%, 71.2%, and 71.9% cases, respectively, with 27.5% (n = 42) of cases being classified as having a germinal center B-cell (GCB) origin by the Hans algorithm. By FISH analysis, 19.6%, 4.6%, 26.1%, and 3.9% cases showed rearrangement at IGH, BCL2, BCL6, and MYC loci, respectively, including three (2.0%) cases of double-hit lymphoma. As compared with the non-GCB tumors, GCB tumors more frequently expressed CD10 (p < 0.001) and bcl-6 (p = 0.001) with less frequent expression of MUM1 (p = 0.007). Moreover, GCB tumors more frequently exhibited rearrangement at the BCL2 (p = 0.024) and MYC (p = 0.038) loci than non-GCB tumors. However, there was no survival difference between these two groups.

Conclusion: In this first series of DLBCL evaluation from Taiwan, we found that the relative frequency of GCB tumors among DLBCL was low in most East Asian countries. There is a wide range of BCL2 rearrangement rates, higher in the West and lower in East Asia. A larger and/or national study is warranted to better understand the immunophenotypic and molecular features of DLBCL in Taiwan and their respective impact on patient survival.
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http://dx.doi.org/10.1016/j.jfma.2016.09.006DOI Listing
November 2016

Clinical parameters for predicting radiation-induced liver disease after intrahepatic reirradiation for hepatocellular carcinoma.

Radiat Oncol 2016 Jul 2;11(1):89. Epub 2016 Jul 2.

Department of Radiation Oncology, Taipei Medical University Hospital, 252, Wu Hsing St., Taipei, 110, Taiwan.

Background: Few data are available on the tolerance of reirradiation in patients with hepatocellular carcinoma (HCC). This study determined the clinical parameters contributing to the development of radiation-induced liver disease (RILD).

Methods: We included 36 patients with HCC who received 2 courses of radiotherapy (RT) to the liver. Using α/β = 15 for tumor and α/β =8 for normal liver tissue for biologically equivalent doses in 2 Gy fractions, mean cumulative to the hepatic tumor and normal liver were 87.7 Gy15 and 31.1 Gy8, respectively. Hepatic toxicities were classified according to the Common Terminology Criteria for Adverse Events, Version 4.0. Clinical data, including liver function test results, radiological study findings, and RT parameters before and after both courses of RT were retrieved for analysis. Using multivariate analysis, logistic regression was used to identify the predictors of RILD, and Cox regression was performed to explore the prognostic factors for overall survival (OS).

Results: Thirteen patients (36 %) developed RILD after reirradiation. Nine of them died because of progressive liver failure without evidence of tumor progression and were categorized to have lethal RILD. A pretreatment Child-Turcotte-Pugh (CTP) score ≥6 was the only predictor of RILD [odds ratio (OR): 15.83, p = 0.001] and lethal RILD [OR: 72.56, p = 0.005]. In addition, a CTP score ≥6 and the presence of portal vein tumor thrombosis before reirradiation were 2 prognostic factors for OS.

Conclusion: Despite a limited sample size, residual liver function using a preirradiation CTP score ≥6 is a clinical parameter associated with an increased risk of RILD in patients requiring hepatic reirradiation.
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http://dx.doi.org/10.1186/s13014-016-0663-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4930588PMC
July 2016

Early radiation-induced liver toxicities are associated with poor survival in patients with advanced hepatocellular carcinoma.

Asia Pac J Clin Oncol 2016 12 7;12(4):437-443. Epub 2016 Mar 7.

Department of Radiation Oncology, China Medical University Hospital, Taichung, Taiwan.

Aim: Little is known about the impact of radiotherapy associated early hepatic toxicities. This study is to investigate the risk factors and outcome of early radiation-induced liver disease (early-RILD) in patients with hepatocellular carcinoma.

Methods: One hundred patients with advanced hepatocellular carcinoma receiving hepatic radiotherapy were included in this retrospective analysis. All had no evidence of intrahepatic tumor progression within 3 months after initiating radiotherapy. The toxicities were graded according to the Common Terminology Criteria for adverse events version 4.0. Early-RILD was defined as any detectable events of RILD occurring during or within 2 weeks after the ending of radiotherapy. Patient- and radiotherapy-related data, and several staging/scoring parameters were retrieved for analysis. Logistic regression analysis was used to find risk factors for early-RILD. Cox regression model was performed to explore prognosticators for survival.

Results: Child-Turcotte-Pugh (CTP) score >5 was the predictor for early-RILD (odds ratio 5.38, P = 0.004). The incidence of early-RILD in patients with CTP scores 6/7 and 5 was 34% and 13.2%, respectively. Early-RILD and a Cancer of the Liver Italian Program (CLIP) score > 2 were the two prognostic factors associated with inferior overall survival (hazard ratio 2.79, P = 0.04; hazard ratio = 3.79, P = 0.04, respectively). The median overall survival for patients with early-RILD was 3.5 months compared with 12.7 months in those without this event.

Conclusion: The occurrence of early-RILD is associated with high mortality. A CTP score >5 is the most informative factor predicting early-RILD.
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http://dx.doi.org/10.1111/ajco.12467DOI Listing
December 2016
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