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Papers by Chyong-huey Lai

Journal of the Formosan Medical Association, Apr 1, 2020

Background/purpose: Ovarian clear cell carcinoma (OCCC) with recurrence/progression after treatme... more Background/purpose: Ovarian clear cell carcinoma (OCCC) with recurrence/progression after treatment has dismal prognosis. We aimed to investigate the management and outcomes of such patients. Methods: OCCC patients who were treated between 2000 and 2013 with cancer recurrence or

Journal of Clinical Oncology, Apr 8, 2000

To compare the efficacy of neoadjuvant chemotherapy (NAC) followed by radical hysterectomy with t... more To compare the efficacy of neoadjuvant chemotherapy (NAC) followed by radical hysterectomy with that of radiotherapy (R/T) for bulky early-stage cervical cancer. Women with previously untreated bulky (primary tumor >/= 4 cm) stage IB or IIA non-small-cell carcinoma of the uterine cervix were randomly assigned to receive either cisplatin 50 mg/m(2) and vincristine 1 mg/m(2) for 1 day and bleomycin 25 mg/m(2) for 3 days for three cycles followed by radical hysterectomy (NAC arm) or receive primary pelvic radiotherapy only (R/T arm). The ratio of patient allocation was 6:4 for the NAC and R/T arms. Women with enlarged para-aortic lymph nodes on image study were ineligible unless results of cytologic or histologic studies were negative. Of the 124 eligible patients, 68 in the NAC arm and 52 in the R/T arm could be evaluated. The median duration of follow-up was 39 months. Thirty-one percent of patients in the NAC arm and 27% in the R/T arm had relapse or persistent diseases after treatment, and 21% in each group died of disease. Estimated cumulative survival rates at 2 years were 81% for the NAC arm and 84% for the R/T arm; the 5-year rates were 70% and 61%, respectively. There were no significant differences in disease-free survival and overall survival. NAC followed by radical hysterectomy and primary R/T showed similar efficacy for bulky stage IB or IIA cervical cancer. Further study to identify patient subgroups better suited for either treatment modality and to evaluate the concurrent use of cisplatin and radiation without routine hysterectomy is necessary.

Journal of Clinical Oncology, Jun 1, 2023

e17611 Background: Based on the TCGA endometrial cancer study results, a clinically applicable cl... more e17611 Background: Based on the TCGA endometrial cancer study results, a clinically applicable classification that identifies distinct subgroups with prognostic signature, the Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE), has been built and validated. It shows that those with abnormal expression of p53 (p53abn) are the group with the worst prognosis. We attempted to explore the association of p53abn and progesterone receptor (PR) in endometrioid endometrial cancer. Methods: We included 397 consecutive endometrial cancer cases of endometrioid histology with adequate tumor tissue in the formalin-fixed, paraffin-embedded (FFPE) block and available follow-up information. This study was granted by Chang Gung Medical Foundation IRB 201702242B0D001. Sanger sequencing to assess the POLE exonuclease domain hotspot mutations of exon 9-14 and immunohistochemical staining on FFPE tumor tissue sections for p53, ER, PR, and mismatch repair proteins were performed. Immunohistochemical p53 expression of cancer cell nucleus was recorded as completely negative (0%), weakly positive (1-59%), and diffusely strong positive (>60%). Tumors with weak positive p53 staining were defined as p53 wild type (p53wt), while the other two were defined as p53 abnormal (p53abn). PR scores were calculated by multiplying the average staining intensity by the tumor cell nucleus stained percentage. We arbitrarily defined a progesterone receptor score of 100 or higher as positive (PR+). Progression-free and endometrial cancer-specific overall survivals starting at the date of diagnosis were evaluated using Kaplan-Meier method and compared by log-rank test between groups. Results: PR was positive in 82% of all studied cases. Of the 48 cases with p53abn tumor, 35(73%) were PR (+). With a median follow-up of 74 months, the progression-free survival and cancer-specific survival of patients with PR+ tumors (N = 310) were 93% and 96.8%, respectively, compared with 75% and 85.7% of those with PR- tumors (N = 70) (both p < 0.001, log-rank test). Among those with P53abn, PR expression was associated with a favorable progression-free survival ( p = 0.081) and better cancer-specific survival ( p = 0.044). POLEmut, POLE mutated; dMMR, deficient mismatch repair PR+, progesterone receptor score ≥100, ER+, estrogen receptor score ≥100; p53abn, abnormal p53 expression. MMR was undetermined in 32 cases, PR in 17 cases, ER in 17 cases, and p53 was undetermined in 10 cases. POLE status was detected in all cases. Cases with POLE wild type, proficient mismatch repair, progesterone score < 100, estrogen score < 100 and wild type p53 were not listed in this table. Conclusions: Our study showed that incorporating PR into prognostic molecular markers for endometrioid endometrial cancer might provide further risk stratification. [Table: see text]

Gynecologic Oncology, Oct 1, 2016

The majority of SEOCs with endometrioid histology were single primary tumors with metastatic dise... more The majority of SEOCs with endometrioid histology were single primary tumors with metastatic disease. • Clinicopathological criteria used to determine SEOCs must be adjusted. • Testing of copy number alterations on SEOCs may help determining the need of adjuvant therapy.

Journal of Personalized Medicine, Feb 18, 2022

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

European Radiology, Dec 6, 2014

To prospectively evaluate the value of CT or MRI (CT/MRI) and PET in the management of vulvar mal... more To prospectively evaluate the value of CT or MRI (CT/MRI) and PET in the management of vulvar malignancies. Abdominal and pelvic CT/MRI and whole-body (18) F-FDG (fluorodeoxyglucose) PET or PET/CT (collectively designated PET hereafter) were performed. Lesion status was determined by the pathological findings or clinical follow-up. The diagnostic efficacy was evaluated by receiver operating characteristic (ROC) curve analysis. The clinical impact of PET was determined on a per scan basis. Twenty-three patients were enrolled, and 38 PET examinations were performed. CT/MRI and PET studies were used for primary staging (n = 17), monitoring the response (n = 7) and restaging after recurrence (n = 14). In primary staging, there was no significant difference between CT/MRI and PET in detecting metastatic inguinal lymph nodes (ILN). CT/MRI was significantly more efficacious than PET in detecting pelvic lymph node (PLN) or distant metastasis (p = 0.007 by ROC per patient basis). PET findings resulted in two positive impacts and one negative impact for both primary staging and restaging. False-positive PLN or distant metastasis PET findings are not uncommon, and hence should be interpreted with caution. PET can be supportive when metastatic ILN/PLN or distant metastasis is suspected on CT/MRI. • False-positive metastatic PLN or distant metastasis PET findings are not uncommon. • CT/MRI has value in the management of vulvar malignancies. • PET can be supportive when metastasis is suspected by CT/MRI.

Primary lymphoma of female genital tract is rare and only 0.3%-1.5% of extra-nodal non Hodgkin' l... more Primary lymphoma of female genital tract is rare and only 0.3%-1.5% of extra-nodal non Hodgkin' lymphomas. The cervix is the second common site in literatures review. The diagnosis is difficult due to submucosal stromal lesion and nonspecific manifestation without constitutional 'B-cell' symptoms. Combined chemotherapy (CHOP) is mainstay for treatment. Methods: Review of a case and literatures. Results: A 39 years-old woman presented to the gynecological clinic with repeated vaginal discharge, pelvic discomfort for 4 months. Her annual Pap test was low-grade squamous intraepithelial lesion. During pelvic examination, a large 6×6 cm. Infiltrative bulky cervical mass was visualized. Rectovaginal examination found cervical tumor extended to parametrial tissue both sides, fixating to the left pelvic sidewall. The colposcopic biopsy result was cervicitis. The deep excisional procedure was performed and result was atypical lymphoid proliferation. Immunohistochemistry (IHC) were positive for CD20, BCL6 (90%), Ki 67 (50%-60%). IHC were negative forAE1/AE3. The diagnosis was diffuse large B-cell lymphoma (WHO Classification 2008). The magnetic resonance imaging show large cervical mass 4.7×4.9×5.3 cm at posterior cervix with invasion to stroma, left parametrium and protrusion into upper vagina. No upper abdominal metastasis and lymphadenopathy were observed. Bone marrow biopsy result was hypocellular and compatible with Ann Arbor stage I. The patient was sent to hematologist and received R-CHOP Cyclophosphamide, Doxorubicin, Vincristine, Prednisone, and Rituximab) for 8 cycles and achieved CR. The patient is remaining remission after 55 months follow up. Conclusion: Primary lymphoma of cervix is extremely rare and deep excisional procedure was useful for diagnosis. CHOP is primary treatment and improved survival outcome.

Modern Pathology, 2020

The molecular underpinnings of seromucinous borderline tumor (SMBT)an uncommon ovarian epithelial... more The molecular underpinnings of seromucinous borderline tumor (SMBT)an uncommon ovarian epithelial neoplasm characterized by association with endometriosis, frequent bilateral ovarian involvement, and occasional progression to invasive carcinomaremain poorly understood. Here, we sought to comprehensively characterize the mutational landscape of SMBT and elucidate the clonal relationship between bilateral ovarian SMBTs. We also compared the mutational profiles between SMBTs and concurrent invasive carcinomas. Formalin-fixed, paraffin-embedded tissue specimens were retrieved from 28 patients diagnosed with SMBT. Massively parallel sequencing of 409 cancer-related genes was conducted to identify somatic mutations in 33 SMBT samples and four concurrent invasive carcinoma specimens. TERT promoter mutations were assessed by Sanger sequencing, whereas immunohistochemistry was used as a surrogate tool for detecting deletions or epigenetic silencing of relevant tumor suppressor genes. Twenty-six (92.9%) of the 28 patients were diagnosed with stage I SMBTs. Seven (25%) cases showed bilateral ovarian involvement and 13 (46%) had concomitant endometriosis. Concurrent ovarian carcinomas were identified in three patients, whereas one case had a synchronous endometrial carcinoma. Somatic mutations in the KRAS, PIK3CA, and ARID1A genes were identified in 100, 60.7, and 14.3% of SMBT samples, respectively. In contrast, TERT promoter mutations and DNA mismatch repair deficiencies were absent. Sequencing of paired specimens from patients with bilateral SMBT revealed the presence of at least two shared somatic mutations, suggestive of a clonal relationship. Similarly, we identified shared somatic mutations between SMBT samples and concurrent ovarian carcinoma specimens. Taken together, these findings demonstrated a distinct mutational landscape of SMBT in which (1) KRAS is invariably mutated, (2) PIK3CA is frequently mutated, and (3) TERT promoter mutations and DNA mismatch repair deficiencies are absent. Our findings represent the first extensive characterization of this rare ovarian neoplasm, with potential implications for disease classification and molecular diagnostics.

Journal of Gynecologic Oncology, 2019

Objectives: An Asian Gynecologic Oncology Group phase III randomized trial was conducted to deter... more Objectives: An Asian Gynecologic Oncology Group phase III randomized trial was conducted to determine whether maintenance chemotherapy could improve progression-free survival (PFS) in stages III/IV ovarian cancer. Methods: Between 2007 and 2014, 45 newly-diagnosed ovarian cancer patients were enrolled after complete remission and randomized (1:1) to arm A (4-weekly carboplatin area under the curve 4 and pegylated liposomal doxorubicin [PLD] 30 mg/m 2 , n=24) for 6 cycles or arm B (observation, n=21). The primary end-point was PFS. A post hoc translational study was conducted to deep sequence BRCA/homologous recombination deficiency (HRD) genes, because BRCA/HRD mutations (BRCA/HRDm) are known to be associated with better prognosis. Results: Enrollment was slow, accrual was closed when 7+ years had passed. With a median

Journal of the Formosan Medical Association = Taiwan yi zhi, Jan 23, 2015

Under-utilization of Papanicolaou (Pap) smear causes a gap in the prevention of cervical neoplasm... more Under-utilization of Papanicolaou (Pap) smear causes a gap in the prevention of cervical neoplasms. A prospective population-based study was conducted investigating whether a self-sampling human papillomavirus (HPV) test was feasible for under-users of Pap smear and factors associated with under-screening in Taiwan. Women not having Pap smear screening for > 5 years were invited to participate in this study. Invitation letters and educational brochures were mailed to 4% of randomly selected eligible women from Taoyuan City, Taiwan, and responders received an HPV self-sampling kit. Those with HPV-positive results were recalled for a Pap smear and colposcopy. Between March 2010 and June 2012, 10,693 women were invited, 354 responded (3.3%), and 282 (2.6%) gave valid informed consent, answered the questionnaire, and submitted HPV samples. The median age of enrolled women was 48.1 years. Forty-seven women (16.7%) had a positive HPV test, and 14 women accepted further survey to find t...

Gynecologic oncology, Jan 28, 2015

A recent randomized trial demonstrated that concurrent chemoradiotherapy (CCRT) with weekly cispl... more A recent randomized trial demonstrated that concurrent chemoradiotherapy (CCRT) with weekly cisplatin and gemcitabine, followed by two adjuvant cycles of cisplatin and gemcitabine improved survival for advanced cervical cancer patients. An Asian Gynecologic Oncology Group (AGOG) study was designed to determine whether only adding gemcitabine in the chemoradiation phase without adjuvant chemotherapy could improve survival. Between March 2009 and March 2013, 74 eligible patients with International Federation of Obstetrics and Gynecology stage III/IVA cervical cancer or stage I/II with positive pelvic/para-aortic nodal metastasis were enrolled. Thirty-seven patients were randomized to arm C (weekly cisplatin 40 mg/m(2)) and 37 patients were randomized to arm CG (weekly cisplatin 40 mg/m(2) and gemcitabine 125 mg/m(2)), for six cycles. Six eligible patients were excluded before the beginning of treatment. An interim analysis showed superimposable progression-free (PFS) and overall survi...

Journal of Molecular Medicine, 2014

Endometrial cancers have been recently molecularly characterized; amplifications of human epiderm... more Endometrial cancers have been recently molecularly characterized; amplifications of human epidermal growth factor receptor 2 (HER2) were seen in 25 % of the serous-like tumors, and mutations in the PI(3)K/AKT pathways were seen in 93 % of endometrioid tumors. These new findings about endometrial cancer suggest a potential for targeted therapy with lapatinib, a dual inhibitor of epidermal growth factor receptor and HER2 tyrosine kinases. However, the clinical efficacy of lapatinib in phase II clinical trials for the treatment of endometrial cancers was only minimal. In this study, we investigated the signaling changes induced by lapatinib in endometrial cancer, which may improve its therapeutic efficacy in molecularly selected patient groups. We identified one of the final molecular targets of lapatinib to be interstitial collagenase, matrix metallopeptidase 1 (MMP1). Lapatinib suppresses MMP1 through EGFR and HER2, and their downstream ERK and AKT signaling pathways. We also found that the activating protein-1 binding site of MMP1 promoter is required for its transcriptional activation, which may be unique for endometrial cancers. Our results also showed that forced expression of active ERK or active AKT mutants rescued MMP1 expression from lapatinib suppression, further suggesting the importance of molecular selection to find appropriate patients with endometrial cancer for future clinical trials with any targeted therapies. Chiao-Yun Lin, Angel Chao, and Tzu-Hao Wang contribute equally to this work.

International Journal of Gynecological Cancer, 2014

Objective: Our aim was to investigate the outcomes and prognostic factors after treatment failure... more Objective: Our aim was to investigate the outcomes and prognostic factors after treatment failure of endometrial cancer. Methods: A total of 923 endometrial cancer patients were treated between 2000 and 2010, of which 109 experienced treatment failure. Treatment failure was defined as relapse after complete removal of all cancerous lesions or persistent/progressive disease despite treatment. Variables including clinicopathological features at initial treatment, type of primary treatment, failure pattern, salvage treatment, and outcomes were analyzed. Kaplan-Meier survival curves were compared with log-rank test. Cox proportional hazards regression model was used to identify significant prognostic factors. Results: Eighteen cases with persistent/progressive disease died shortly from primary diagnosis (1Y23 months). The remaining 91 patients had recurrences in vagina only (8.8%), pelvis (3.3%), distant (63.7%), and combined pelvic-distant sites (24.2%). Median time to recurrence was 13.3 months (3.2Y97.2 months). The median follow-up after recurrence of survivors was 60.5 months (10.6Y121.7 months). The median survival after recurrence (SAR) was 20.3 months (1.9Y121.7 months) with 5-year SAR rate of 32.4%. By multivariate analysis, initial stage II to IV (hazards ratio [HR], 3.41; 1.53Y7.60; P = 0.003), type II histology (HR, 2.50; 1.28Y4.90; P = 0.008), positive peritoneal cytology (HR, 2.23; 1.07Y4.68; P = 0.033), and recurrence at multiple sites (HR, 2.51; 1.30Y4.84; P = 0.006) were significantly associated with poor SAR. The 5-year SAR rates in patients with solitary vaginal, nodal/ liver, or pulmonary/bony recurrence were 83.3%, 50.5%, and 24.2%, respectively. Ten cases with resectable or irradiatable recurrence at multiple sites or multiple relapses attained SAR greater than 5 years after multimodality salvage therapy. Conclusions: Initial stage II to IV, type 2 histology, positive cytology, and recurrence at multiple sites were significant poor prognostic factors. Curative intent salvage therapy remains a viable option for cases with resectable or irradiatable multiple recurrences and solitary distant metastasis.

Journal of Molecular Medicine, 2012

Unopposed estrogen exposure is an important factor in the tumorigenesis of endometrial cancer. Nu... more Unopposed estrogen exposure is an important factor in the tumorigenesis of endometrial cancer. Nucleophosmin/B23 (NPM/B23), a phosphoprotein that has pleiotropic functions in cells, plays an important role in various cancers. However, the regulatory role of NPM/B23 in estrogen signaling in endometrial cancer has not been explored. Here, we report that NPM/B23 was required for estrogen-induced endometrial proliferation, and the increase in NPM/B23 was estrogen receptor α-dependent. Furthermore, estrogen increased NPM/B23 protein levels by repressing its ubiquitination and subsequently stabilizing the protein. The overexpression of the alternate reading frame (ARF) suppressed the estrogen-induced increase in the NPM/B23 protein levels, indicating that ARF inhibited the observed estrogen-mediated NPM/B23 stabilization. Our results suggest that one of the effects of estrogen on endometrial proliferation is the suppression of the NPM/B23-ARF interaction and the subsequent increase in NPM/B23 protein levels. This novel characterization of NPM/B23 in estrogen-mediated cell proliferation may extend our understanding of the tumorigenesis of steroid hormone-related cancers.

Immunology Letters, 2007

DNA vaccination has emerged as a promising strategy for cancer immunotherapy. However, since DNA ... more DNA vaccination has emerged as a promising strategy for cancer immunotherapy. However, since DNA vaccines have low immunogenicity, various strategies have been developed to enhance the potency of DNA vaccines. In the current study, we aim to determine whether the potency of the DNA vaccine encoding human papillomavirus type 16 (HPV-16) E7 antigen can be enhanced by IL-2. We have generated a DNA vaccine encoding IL-2 linked to HPV-16 E7 antigen. Our results indicate that the DNA vaccine encoding a fusion of IL-2 and E7 proteins generated the highest frequency of E7specific CD8 + T cells. We also found that the DNA vaccine encoding a fusion of IL-2 and E7 proteins generated the strongest protective as well as therapeutic anti-tumor effect against E7-expressing tumors. In addition, it was observed that CD8 + T cells were mainly responsible for the antitumor effect generated by the DNA vaccine encoding a fusion of IL-2 and E7 proteins. Thus, we conclude that the linkage of IL-2 to HPV-16 E7 antigen significantly enhances the DNA vaccine potency against E7-expressing tumors. Our strategy may potentially be used in other antigenic systems to control infectious diseases and/or cancer.

Gynecologic Oncology, 2012

Our aim was to investigate the clinical features and outcomes following recurrence after primary ... more Our aim was to investigate the clinical features and outcomes following recurrence after primary radical hysterectomy for cervical cancer. Clinical data of 121 documented recurrent cervical cancer patients who received primary radical hysterectomy and bilateral pelvic lymphadenectomy between 1993 and 2000 at Chang Gung Memorial Hospital were retrospectively reviewed. Clinicopathological variables, primary treatment, failure pattern, salvage treatment and outcomes were analyzed. Outcomes of the current study were compared to those treated between 1982 and 1992 (1982-1992 cohort). Cancer recurrence was documented at a median time to recurrence (TTR) of 28.4 months (1.2-129.9 months). Assessable failure patterns (n=106) included loco-regional in 46.3%, distant in 47.2% and combined pelvic-distant in 6.6%. 5-year survival of the 121 patients was 22.3% after cancer recurrence. The median survival after recurrence (SAR) was 16.4 months (range 0-144.2 months). By multivariate analysis, extravaginal sites of recurrence (HR 2.56, 1.28-5.12; p=0.008) and HPV16-positive (HR 0.60, 0.38-0.96; p=0.033) were significant prognostic factors for SAR. Non-squamous histology or pelvic node metastasis at primary surgery were not significant (5-year SAR of 16.4% and 20.0%, respectively), though they were (0% and 0%) in the 1993-2000 cohort. Salvage surgery and concurrent chemoradiation were more frequently used in the 1993-2000 cohort (48.3% versus 12.4%). HPV16-negativity and extravaginal relapse were significant poor prognostic factors. Future randomized controlled trials for recurrent cervical cancer could be stratified for these two factors if further studies using external validation confirm these results.

Gynecologic Oncology, 2005

Background. There have been several reports about successful fertility-preserving treatment of en... more Background. There have been several reports about successful fertility-preserving treatment of endometrial carcinoma with subsequent pregnancy. However, conservative hormonal treatment for early-stage endometrial cancer still entails some risk. Case. We present a 36-year-old nulliparous woman, initially diagnosed as clinical stage IA, grade 1 endometrial adenocarcinoma, receiving 6-month conservative treatment with remission achieved at 4 months from diagnosis. Recurrence at the endometrium was documented at the end of treatment. She underwent a definitive surgery including total hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymph node dissection. The final pathology revealed well-differentiated endometrioid adenocarcinoma with inner one-third myometrial invasion and right ovarian metastasis. Conclusion. This case report signals a warning that negative preoperative imaging studies are not reassuring for a relapsing low-grade, early-stage endometrial carcinoma failing conservative treatment.

Gynecologic Oncology, 2005

This study was undertaken to investigate the outcome and prognostic factors in patients with ovar... more This study was undertaken to investigate the outcome and prognostic factors in patients with ovarian germ cell malignancies (OGCMs). A total of 93 patients with OGCMs were retrospectively reviewed, among whom 84 patients had primary treatment at Chang Gung Memorial Hospital (CGMH) between 1984 and 2003. The other nine patients were primarily treated outside and referred for follow-up (n = 1), adjuvant chemotherapy (n = 4), or salvage therapy after recurrence (n = 4). The clinicopathological and treatment-related characteristics were analyzed for association with the occurrence of tumor persistence/recurrence or death. Of the study patients, 32 had dysgerminoma (DSG), 29 immature teratoma (IMT), 23 endodermal sinus tumor, 7 mixed germ cell tumors, and 1 each had choriocarcinoma and embryonal carcinoma. The median follow-up of survivors was 66 months (range, 12-236 months). The median time to recurrence or progression was 8 months. There were 11 treatment failures with 6 died of cancer. The 5-year survival rate was 97.4% for those primarily treated at CGMH. Histology (DSG/IMT versus non-DSG/IMT) (P < 0.0001) and International Federation of Gynecology and Obstetrics stage (P = 0.001) were significantly associated with treatment failure, while histology (P = 0.0004), salvage high-dose chemotherapy (HD-CT) after primary chemotherapy failed (P = 0.0405), and residual tumor after salvage surgery (P = 0.0014) were significant prognostic factors for overall survival. Prognosis of OGCMs is excellent if managed with standard treatment initially. Aggressive HD-CT with salvage surgery needs to be applied for recurrent/persistent disease after primary chemotherapy.

European Journal of Nuclear Medicine and Molecular Imaging, 2005

Compared with computed tomography (CT) and magnetic resonance imaging (MRI), positron emission to... more Compared with computed tomography (CT) and magnetic resonance imaging (MRI), positron emission tomography (PET) may have additional value in the assessment of primary and recurrent cervical cancer. However, the degree of tumour uptake of (18)F-2-fluoro-2-deoxy-D: -glucose (FDG) uptake is sometimes influenced by diabetes mellitus (DM). Therefore, we conducted this prospective study to compare the diagnostic ability of FDG-PET in patients with cervical cancer complicated by DM and those without DM. Patients with untreated locally advanced primary or clinically curable recurrent cervical carcinoma were enrolled. Both FDG-PET and MRI/CT scans were performed within 2 weeks. Patients were categorised into the following groups: hyperglycaemic DM (fasting blood sugar >126 mg/dl), euglycaemic DM and non-DM. The lesions were confirmed histologically or by clinical follow-up. The receiver operating characteristic curve method, with calculation of the area under the curve (AUC), was used to evaluate the discriminative power. From February 2001 to January 2003, 219 patients (75 with primary and 144 with recurrent cervical cancer) were eligible for analysis. Sixteen had hyperglycaemic DM, 12 had euglycaemic DM and 191 were in the non-DM group. The diagnostic power of PET in the hyperglycaemic DM, euglycaemic DM and non-DM groups did not differ significantly with regard to the identification of either metastatic lesions (AUC, 0.967/0.947/0.925, P>0.05) or primary tumours/local recurrence (AUC, 0.950/0.938/0.979, P>0.05). Considering all DM patients, PET showed a significantly higher detection power than MRI/CT scans in respect of metastatic lesions (AUC=0.956 vs 0.824, P=0.012). In comparison with its accuracy in non-DM patients, the accuracy of PET in cervical cancer patients with mild to moderate DM was not significantly reduced.

Journal of the Formosan Medical Association, Apr 1, 2020

Background/purpose: Ovarian clear cell carcinoma (OCCC) with recurrence/progression after treatme... more Background/purpose: Ovarian clear cell carcinoma (OCCC) with recurrence/progression after treatment has dismal prognosis. We aimed to investigate the management and outcomes of such patients. Methods: OCCC patients who were treated between 2000 and 2013 with cancer recurrence or

Journal of Clinical Oncology, Apr 8, 2000

To compare the efficacy of neoadjuvant chemotherapy (NAC) followed by radical hysterectomy with t... more To compare the efficacy of neoadjuvant chemotherapy (NAC) followed by radical hysterectomy with that of radiotherapy (R/T) for bulky early-stage cervical cancer. Women with previously untreated bulky (primary tumor >/= 4 cm) stage IB or IIA non-small-cell carcinoma of the uterine cervix were randomly assigned to receive either cisplatin 50 mg/m(2) and vincristine 1 mg/m(2) for 1 day and bleomycin 25 mg/m(2) for 3 days for three cycles followed by radical hysterectomy (NAC arm) or receive primary pelvic radiotherapy only (R/T arm). The ratio of patient allocation was 6:4 for the NAC and R/T arms. Women with enlarged para-aortic lymph nodes on image study were ineligible unless results of cytologic or histologic studies were negative. Of the 124 eligible patients, 68 in the NAC arm and 52 in the R/T arm could be evaluated. The median duration of follow-up was 39 months. Thirty-one percent of patients in the NAC arm and 27% in the R/T arm had relapse or persistent diseases after treatment, and 21% in each group died of disease. Estimated cumulative survival rates at 2 years were 81% for the NAC arm and 84% for the R/T arm; the 5-year rates were 70% and 61%, respectively. There were no significant differences in disease-free survival and overall survival. NAC followed by radical hysterectomy and primary R/T showed similar efficacy for bulky stage IB or IIA cervical cancer. Further study to identify patient subgroups better suited for either treatment modality and to evaluate the concurrent use of cisplatin and radiation without routine hysterectomy is necessary.

Journal of Clinical Oncology, Jun 1, 2023

e17611 Background: Based on the TCGA endometrial cancer study results, a clinically applicable cl... more e17611 Background: Based on the TCGA endometrial cancer study results, a clinically applicable classification that identifies distinct subgroups with prognostic signature, the Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE), has been built and validated. It shows that those with abnormal expression of p53 (p53abn) are the group with the worst prognosis. We attempted to explore the association of p53abn and progesterone receptor (PR) in endometrioid endometrial cancer. Methods: We included 397 consecutive endometrial cancer cases of endometrioid histology with adequate tumor tissue in the formalin-fixed, paraffin-embedded (FFPE) block and available follow-up information. This study was granted by Chang Gung Medical Foundation IRB 201702242B0D001. Sanger sequencing to assess the POLE exonuclease domain hotspot mutations of exon 9-14 and immunohistochemical staining on FFPE tumor tissue sections for p53, ER, PR, and mismatch repair proteins were performed. Immunohistochemical p53 expression of cancer cell nucleus was recorded as completely negative (0%), weakly positive (1-59%), and diffusely strong positive (>60%). Tumors with weak positive p53 staining were defined as p53 wild type (p53wt), while the other two were defined as p53 abnormal (p53abn). PR scores were calculated by multiplying the average staining intensity by the tumor cell nucleus stained percentage. We arbitrarily defined a progesterone receptor score of 100 or higher as positive (PR+). Progression-free and endometrial cancer-specific overall survivals starting at the date of diagnosis were evaluated using Kaplan-Meier method and compared by log-rank test between groups. Results: PR was positive in 82% of all studied cases. Of the 48 cases with p53abn tumor, 35(73%) were PR (+). With a median follow-up of 74 months, the progression-free survival and cancer-specific survival of patients with PR+ tumors (N = 310) were 93% and 96.8%, respectively, compared with 75% and 85.7% of those with PR- tumors (N = 70) (both p < 0.001, log-rank test). Among those with P53abn, PR expression was associated with a favorable progression-free survival ( p = 0.081) and better cancer-specific survival ( p = 0.044). POLEmut, POLE mutated; dMMR, deficient mismatch repair PR+, progesterone receptor score ≥100, ER+, estrogen receptor score ≥100; p53abn, abnormal p53 expression. MMR was undetermined in 32 cases, PR in 17 cases, ER in 17 cases, and p53 was undetermined in 10 cases. POLE status was detected in all cases. Cases with POLE wild type, proficient mismatch repair, progesterone score < 100, estrogen score < 100 and wild type p53 were not listed in this table. Conclusions: Our study showed that incorporating PR into prognostic molecular markers for endometrioid endometrial cancer might provide further risk stratification. [Table: see text]

Gynecologic Oncology, Oct 1, 2016

The majority of SEOCs with endometrioid histology were single primary tumors with metastatic dise... more The majority of SEOCs with endometrioid histology were single primary tumors with metastatic disease. • Clinicopathological criteria used to determine SEOCs must be adjusted. • Testing of copy number alterations on SEOCs may help determining the need of adjuvant therapy.

Journal of Personalized Medicine, Feb 18, 2022

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

European Radiology, Dec 6, 2014

To prospectively evaluate the value of CT or MRI (CT/MRI) and PET in the management of vulvar mal... more To prospectively evaluate the value of CT or MRI (CT/MRI) and PET in the management of vulvar malignancies. Abdominal and pelvic CT/MRI and whole-body (18) F-FDG (fluorodeoxyglucose) PET or PET/CT (collectively designated PET hereafter) were performed. Lesion status was determined by the pathological findings or clinical follow-up. The diagnostic efficacy was evaluated by receiver operating characteristic (ROC) curve analysis. The clinical impact of PET was determined on a per scan basis. Twenty-three patients were enrolled, and 38 PET examinations were performed. CT/MRI and PET studies were used for primary staging (n = 17), monitoring the response (n = 7) and restaging after recurrence (n = 14). In primary staging, there was no significant difference between CT/MRI and PET in detecting metastatic inguinal lymph nodes (ILN). CT/MRI was significantly more efficacious than PET in detecting pelvic lymph node (PLN) or distant metastasis (p = 0.007 by ROC per patient basis). PET findings resulted in two positive impacts and one negative impact for both primary staging and restaging. False-positive PLN or distant metastasis PET findings are not uncommon, and hence should be interpreted with caution. PET can be supportive when metastatic ILN/PLN or distant metastasis is suspected on CT/MRI. • False-positive metastatic PLN or distant metastasis PET findings are not uncommon. • CT/MRI has value in the management of vulvar malignancies. • PET can be supportive when metastasis is suspected by CT/MRI.

Primary lymphoma of female genital tract is rare and only 0.3%-1.5% of extra-nodal non Hodgkin' l... more Primary lymphoma of female genital tract is rare and only 0.3%-1.5% of extra-nodal non Hodgkin' lymphomas. The cervix is the second common site in literatures review. The diagnosis is difficult due to submucosal stromal lesion and nonspecific manifestation without constitutional 'B-cell' symptoms. Combined chemotherapy (CHOP) is mainstay for treatment. Methods: Review of a case and literatures. Results: A 39 years-old woman presented to the gynecological clinic with repeated vaginal discharge, pelvic discomfort for 4 months. Her annual Pap test was low-grade squamous intraepithelial lesion. During pelvic examination, a large 6×6 cm. Infiltrative bulky cervical mass was visualized. Rectovaginal examination found cervical tumor extended to parametrial tissue both sides, fixating to the left pelvic sidewall. The colposcopic biopsy result was cervicitis. The deep excisional procedure was performed and result was atypical lymphoid proliferation. Immunohistochemistry (IHC) were positive for CD20, BCL6 (90%), Ki 67 (50%-60%). IHC were negative forAE1/AE3. The diagnosis was diffuse large B-cell lymphoma (WHO Classification 2008). The magnetic resonance imaging show large cervical mass 4.7×4.9×5.3 cm at posterior cervix with invasion to stroma, left parametrium and protrusion into upper vagina. No upper abdominal metastasis and lymphadenopathy were observed. Bone marrow biopsy result was hypocellular and compatible with Ann Arbor stage I. The patient was sent to hematologist and received R-CHOP Cyclophosphamide, Doxorubicin, Vincristine, Prednisone, and Rituximab) for 8 cycles and achieved CR. The patient is remaining remission after 55 months follow up. Conclusion: Primary lymphoma of cervix is extremely rare and deep excisional procedure was useful for diagnosis. CHOP is primary treatment and improved survival outcome.

Modern Pathology, 2020

The molecular underpinnings of seromucinous borderline tumor (SMBT)an uncommon ovarian epithelial... more The molecular underpinnings of seromucinous borderline tumor (SMBT)an uncommon ovarian epithelial neoplasm characterized by association with endometriosis, frequent bilateral ovarian involvement, and occasional progression to invasive carcinomaremain poorly understood. Here, we sought to comprehensively characterize the mutational landscape of SMBT and elucidate the clonal relationship between bilateral ovarian SMBTs. We also compared the mutational profiles between SMBTs and concurrent invasive carcinomas. Formalin-fixed, paraffin-embedded tissue specimens were retrieved from 28 patients diagnosed with SMBT. Massively parallel sequencing of 409 cancer-related genes was conducted to identify somatic mutations in 33 SMBT samples and four concurrent invasive carcinoma specimens. TERT promoter mutations were assessed by Sanger sequencing, whereas immunohistochemistry was used as a surrogate tool for detecting deletions or epigenetic silencing of relevant tumor suppressor genes. Twenty-six (92.9%) of the 28 patients were diagnosed with stage I SMBTs. Seven (25%) cases showed bilateral ovarian involvement and 13 (46%) had concomitant endometriosis. Concurrent ovarian carcinomas were identified in three patients, whereas one case had a synchronous endometrial carcinoma. Somatic mutations in the KRAS, PIK3CA, and ARID1A genes were identified in 100, 60.7, and 14.3% of SMBT samples, respectively. In contrast, TERT promoter mutations and DNA mismatch repair deficiencies were absent. Sequencing of paired specimens from patients with bilateral SMBT revealed the presence of at least two shared somatic mutations, suggestive of a clonal relationship. Similarly, we identified shared somatic mutations between SMBT samples and concurrent ovarian carcinoma specimens. Taken together, these findings demonstrated a distinct mutational landscape of SMBT in which (1) KRAS is invariably mutated, (2) PIK3CA is frequently mutated, and (3) TERT promoter mutations and DNA mismatch repair deficiencies are absent. Our findings represent the first extensive characterization of this rare ovarian neoplasm, with potential implications for disease classification and molecular diagnostics.

Journal of Gynecologic Oncology, 2019

Objectives: An Asian Gynecologic Oncology Group phase III randomized trial was conducted to deter... more Objectives: An Asian Gynecologic Oncology Group phase III randomized trial was conducted to determine whether maintenance chemotherapy could improve progression-free survival (PFS) in stages III/IV ovarian cancer. Methods: Between 2007 and 2014, 45 newly-diagnosed ovarian cancer patients were enrolled after complete remission and randomized (1:1) to arm A (4-weekly carboplatin area under the curve 4 and pegylated liposomal doxorubicin [PLD] 30 mg/m 2 , n=24) for 6 cycles or arm B (observation, n=21). The primary end-point was PFS. A post hoc translational study was conducted to deep sequence BRCA/homologous recombination deficiency (HRD) genes, because BRCA/HRD mutations (BRCA/HRDm) are known to be associated with better prognosis. Results: Enrollment was slow, accrual was closed when 7+ years had passed. With a median

Journal of the Formosan Medical Association = Taiwan yi zhi, Jan 23, 2015

Under-utilization of Papanicolaou (Pap) smear causes a gap in the prevention of cervical neoplasm... more Under-utilization of Papanicolaou (Pap) smear causes a gap in the prevention of cervical neoplasms. A prospective population-based study was conducted investigating whether a self-sampling human papillomavirus (HPV) test was feasible for under-users of Pap smear and factors associated with under-screening in Taiwan. Women not having Pap smear screening for > 5 years were invited to participate in this study. Invitation letters and educational brochures were mailed to 4% of randomly selected eligible women from Taoyuan City, Taiwan, and responders received an HPV self-sampling kit. Those with HPV-positive results were recalled for a Pap smear and colposcopy. Between March 2010 and June 2012, 10,693 women were invited, 354 responded (3.3%), and 282 (2.6%) gave valid informed consent, answered the questionnaire, and submitted HPV samples. The median age of enrolled women was 48.1 years. Forty-seven women (16.7%) had a positive HPV test, and 14 women accepted further survey to find t...

Gynecologic oncology, Jan 28, 2015

A recent randomized trial demonstrated that concurrent chemoradiotherapy (CCRT) with weekly cispl... more A recent randomized trial demonstrated that concurrent chemoradiotherapy (CCRT) with weekly cisplatin and gemcitabine, followed by two adjuvant cycles of cisplatin and gemcitabine improved survival for advanced cervical cancer patients. An Asian Gynecologic Oncology Group (AGOG) study was designed to determine whether only adding gemcitabine in the chemoradiation phase without adjuvant chemotherapy could improve survival. Between March 2009 and March 2013, 74 eligible patients with International Federation of Obstetrics and Gynecology stage III/IVA cervical cancer or stage I/II with positive pelvic/para-aortic nodal metastasis were enrolled. Thirty-seven patients were randomized to arm C (weekly cisplatin 40 mg/m(2)) and 37 patients were randomized to arm CG (weekly cisplatin 40 mg/m(2) and gemcitabine 125 mg/m(2)), for six cycles. Six eligible patients were excluded before the beginning of treatment. An interim analysis showed superimposable progression-free (PFS) and overall survi...

Journal of Molecular Medicine, 2014

Endometrial cancers have been recently molecularly characterized; amplifications of human epiderm... more Endometrial cancers have been recently molecularly characterized; amplifications of human epidermal growth factor receptor 2 (HER2) were seen in 25 % of the serous-like tumors, and mutations in the PI(3)K/AKT pathways were seen in 93 % of endometrioid tumors. These new findings about endometrial cancer suggest a potential for targeted therapy with lapatinib, a dual inhibitor of epidermal growth factor receptor and HER2 tyrosine kinases. However, the clinical efficacy of lapatinib in phase II clinical trials for the treatment of endometrial cancers was only minimal. In this study, we investigated the signaling changes induced by lapatinib in endometrial cancer, which may improve its therapeutic efficacy in molecularly selected patient groups. We identified one of the final molecular targets of lapatinib to be interstitial collagenase, matrix metallopeptidase 1 (MMP1). Lapatinib suppresses MMP1 through EGFR and HER2, and their downstream ERK and AKT signaling pathways. We also found that the activating protein-1 binding site of MMP1 promoter is required for its transcriptional activation, which may be unique for endometrial cancers. Our results also showed that forced expression of active ERK or active AKT mutants rescued MMP1 expression from lapatinib suppression, further suggesting the importance of molecular selection to find appropriate patients with endometrial cancer for future clinical trials with any targeted therapies. Chiao-Yun Lin, Angel Chao, and Tzu-Hao Wang contribute equally to this work.

International Journal of Gynecological Cancer, 2014

Objective: Our aim was to investigate the outcomes and prognostic factors after treatment failure... more Objective: Our aim was to investigate the outcomes and prognostic factors after treatment failure of endometrial cancer. Methods: A total of 923 endometrial cancer patients were treated between 2000 and 2010, of which 109 experienced treatment failure. Treatment failure was defined as relapse after complete removal of all cancerous lesions or persistent/progressive disease despite treatment. Variables including clinicopathological features at initial treatment, type of primary treatment, failure pattern, salvage treatment, and outcomes were analyzed. Kaplan-Meier survival curves were compared with log-rank test. Cox proportional hazards regression model was used to identify significant prognostic factors. Results: Eighteen cases with persistent/progressive disease died shortly from primary diagnosis (1Y23 months). The remaining 91 patients had recurrences in vagina only (8.8%), pelvis (3.3%), distant (63.7%), and combined pelvic-distant sites (24.2%). Median time to recurrence was 13.3 months (3.2Y97.2 months). The median follow-up after recurrence of survivors was 60.5 months (10.6Y121.7 months). The median survival after recurrence (SAR) was 20.3 months (1.9Y121.7 months) with 5-year SAR rate of 32.4%. By multivariate analysis, initial stage II to IV (hazards ratio [HR], 3.41; 1.53Y7.60; P = 0.003), type II histology (HR, 2.50; 1.28Y4.90; P = 0.008), positive peritoneal cytology (HR, 2.23; 1.07Y4.68; P = 0.033), and recurrence at multiple sites (HR, 2.51; 1.30Y4.84; P = 0.006) were significantly associated with poor SAR. The 5-year SAR rates in patients with solitary vaginal, nodal/ liver, or pulmonary/bony recurrence were 83.3%, 50.5%, and 24.2%, respectively. Ten cases with resectable or irradiatable recurrence at multiple sites or multiple relapses attained SAR greater than 5 years after multimodality salvage therapy. Conclusions: Initial stage II to IV, type 2 histology, positive cytology, and recurrence at multiple sites were significant poor prognostic factors. Curative intent salvage therapy remains a viable option for cases with resectable or irradiatable multiple recurrences and solitary distant metastasis.

Journal of Molecular Medicine, 2012

Unopposed estrogen exposure is an important factor in the tumorigenesis of endometrial cancer. Nu... more Unopposed estrogen exposure is an important factor in the tumorigenesis of endometrial cancer. Nucleophosmin/B23 (NPM/B23), a phosphoprotein that has pleiotropic functions in cells, plays an important role in various cancers. However, the regulatory role of NPM/B23 in estrogen signaling in endometrial cancer has not been explored. Here, we report that NPM/B23 was required for estrogen-induced endometrial proliferation, and the increase in NPM/B23 was estrogen receptor α-dependent. Furthermore, estrogen increased NPM/B23 protein levels by repressing its ubiquitination and subsequently stabilizing the protein. The overexpression of the alternate reading frame (ARF) suppressed the estrogen-induced increase in the NPM/B23 protein levels, indicating that ARF inhibited the observed estrogen-mediated NPM/B23 stabilization. Our results suggest that one of the effects of estrogen on endometrial proliferation is the suppression of the NPM/B23-ARF interaction and the subsequent increase in NPM/B23 protein levels. This novel characterization of NPM/B23 in estrogen-mediated cell proliferation may extend our understanding of the tumorigenesis of steroid hormone-related cancers.

Immunology Letters, 2007

DNA vaccination has emerged as a promising strategy for cancer immunotherapy. However, since DNA ... more DNA vaccination has emerged as a promising strategy for cancer immunotherapy. However, since DNA vaccines have low immunogenicity, various strategies have been developed to enhance the potency of DNA vaccines. In the current study, we aim to determine whether the potency of the DNA vaccine encoding human papillomavirus type 16 (HPV-16) E7 antigen can be enhanced by IL-2. We have generated a DNA vaccine encoding IL-2 linked to HPV-16 E7 antigen. Our results indicate that the DNA vaccine encoding a fusion of IL-2 and E7 proteins generated the highest frequency of E7specific CD8 + T cells. We also found that the DNA vaccine encoding a fusion of IL-2 and E7 proteins generated the strongest protective as well as therapeutic anti-tumor effect against E7-expressing tumors. In addition, it was observed that CD8 + T cells were mainly responsible for the antitumor effect generated by the DNA vaccine encoding a fusion of IL-2 and E7 proteins. Thus, we conclude that the linkage of IL-2 to HPV-16 E7 antigen significantly enhances the DNA vaccine potency against E7-expressing tumors. Our strategy may potentially be used in other antigenic systems to control infectious diseases and/or cancer.

Gynecologic Oncology, 2012

Our aim was to investigate the clinical features and outcomes following recurrence after primary ... more Our aim was to investigate the clinical features and outcomes following recurrence after primary radical hysterectomy for cervical cancer. Clinical data of 121 documented recurrent cervical cancer patients who received primary radical hysterectomy and bilateral pelvic lymphadenectomy between 1993 and 2000 at Chang Gung Memorial Hospital were retrospectively reviewed. Clinicopathological variables, primary treatment, failure pattern, salvage treatment and outcomes were analyzed. Outcomes of the current study were compared to those treated between 1982 and 1992 (1982-1992 cohort). Cancer recurrence was documented at a median time to recurrence (TTR) of 28.4 months (1.2-129.9 months). Assessable failure patterns (n=106) included loco-regional in 46.3%, distant in 47.2% and combined pelvic-distant in 6.6%. 5-year survival of the 121 patients was 22.3% after cancer recurrence. The median survival after recurrence (SAR) was 16.4 months (range 0-144.2 months). By multivariate analysis, extravaginal sites of recurrence (HR 2.56, 1.28-5.12; p=0.008) and HPV16-positive (HR 0.60, 0.38-0.96; p=0.033) were significant prognostic factors for SAR. Non-squamous histology or pelvic node metastasis at primary surgery were not significant (5-year SAR of 16.4% and 20.0%, respectively), though they were (0% and 0%) in the 1993-2000 cohort. Salvage surgery and concurrent chemoradiation were more frequently used in the 1993-2000 cohort (48.3% versus 12.4%). HPV16-negativity and extravaginal relapse were significant poor prognostic factors. Future randomized controlled trials for recurrent cervical cancer could be stratified for these two factors if further studies using external validation confirm these results.

Gynecologic Oncology, 2005

Background. There have been several reports about successful fertility-preserving treatment of en... more Background. There have been several reports about successful fertility-preserving treatment of endometrial carcinoma with subsequent pregnancy. However, conservative hormonal treatment for early-stage endometrial cancer still entails some risk. Case. We present a 36-year-old nulliparous woman, initially diagnosed as clinical stage IA, grade 1 endometrial adenocarcinoma, receiving 6-month conservative treatment with remission achieved at 4 months from diagnosis. Recurrence at the endometrium was documented at the end of treatment. She underwent a definitive surgery including total hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymph node dissection. The final pathology revealed well-differentiated endometrioid adenocarcinoma with inner one-third myometrial invasion and right ovarian metastasis. Conclusion. This case report signals a warning that negative preoperative imaging studies are not reassuring for a relapsing low-grade, early-stage endometrial carcinoma failing conservative treatment.

Gynecologic Oncology, 2005

This study was undertaken to investigate the outcome and prognostic factors in patients with ovar... more This study was undertaken to investigate the outcome and prognostic factors in patients with ovarian germ cell malignancies (OGCMs). A total of 93 patients with OGCMs were retrospectively reviewed, among whom 84 patients had primary treatment at Chang Gung Memorial Hospital (CGMH) between 1984 and 2003. The other nine patients were primarily treated outside and referred for follow-up (n = 1), adjuvant chemotherapy (n = 4), or salvage therapy after recurrence (n = 4). The clinicopathological and treatment-related characteristics were analyzed for association with the occurrence of tumor persistence/recurrence or death. Of the study patients, 32 had dysgerminoma (DSG), 29 immature teratoma (IMT), 23 endodermal sinus tumor, 7 mixed germ cell tumors, and 1 each had choriocarcinoma and embryonal carcinoma. The median follow-up of survivors was 66 months (range, 12-236 months). The median time to recurrence or progression was 8 months. There were 11 treatment failures with 6 died of cancer. The 5-year survival rate was 97.4% for those primarily treated at CGMH. Histology (DSG/IMT versus non-DSG/IMT) (P < 0.0001) and International Federation of Gynecology and Obstetrics stage (P = 0.001) were significantly associated with treatment failure, while histology (P = 0.0004), salvage high-dose chemotherapy (HD-CT) after primary chemotherapy failed (P = 0.0405), and residual tumor after salvage surgery (P = 0.0014) were significant prognostic factors for overall survival. Prognosis of OGCMs is excellent if managed with standard treatment initially. Aggressive HD-CT with salvage surgery needs to be applied for recurrent/persistent disease after primary chemotherapy.

European Journal of Nuclear Medicine and Molecular Imaging, 2005

Compared with computed tomography (CT) and magnetic resonance imaging (MRI), positron emission to... more Compared with computed tomography (CT) and magnetic resonance imaging (MRI), positron emission tomography (PET) may have additional value in the assessment of primary and recurrent cervical cancer. However, the degree of tumour uptake of (18)F-2-fluoro-2-deoxy-D: -glucose (FDG) uptake is sometimes influenced by diabetes mellitus (DM). Therefore, we conducted this prospective study to compare the diagnostic ability of FDG-PET in patients with cervical cancer complicated by DM and those without DM. Patients with untreated locally advanced primary or clinically curable recurrent cervical carcinoma were enrolled. Both FDG-PET and MRI/CT scans were performed within 2 weeks. Patients were categorised into the following groups: hyperglycaemic DM (fasting blood sugar >126 mg/dl), euglycaemic DM and non-DM. The lesions were confirmed histologically or by clinical follow-up. The receiver operating characteristic curve method, with calculation of the area under the curve (AUC), was used to evaluate the discriminative power. From February 2001 to January 2003, 219 patients (75 with primary and 144 with recurrent cervical cancer) were eligible for analysis. Sixteen had hyperglycaemic DM, 12 had euglycaemic DM and 191 were in the non-DM group. The diagnostic power of PET in the hyperglycaemic DM, euglycaemic DM and non-DM groups did not differ significantly with regard to the identification of either metastatic lesions (AUC, 0.967/0.947/0.925, P>0.05) or primary tumours/local recurrence (AUC, 0.950/0.938/0.979, P>0.05). Considering all DM patients, PET showed a significantly higher detection power than MRI/CT scans in respect of metastatic lesions (AUC=0.956 vs 0.824, P=0.012). In comparison with its accuracy in non-DM patients, the accuracy of PET in cervical cancer patients with mild to moderate DM was not significantly reduced.