Lan-Yan Yang

Comparison of the diagnostic accuracy of contrast-enhanced MRI and diffusion-weighted MRI in the differentiation between uterine leiomyosarcoma / smooth muscle tumor with uncertain malignant potential and benign leiomyoma.

To compare the diagnostic accuracy of contrast‐enhanced (CE) magnetic resonance imaging (MRI) and diffusion‐weighted MRI (DWI) in the differentiation between uterine leiomyosarcoma (LMS) / smooth muscle tumor with uncertain malignant potential (STUMP) and benign leiomyoma.

A randomized trial comparing concurrent chemoradiotherapy with single-agent cisplatin versus cisplatin plus gemcitabine in patients with advanced cervical cancer: An Asian Gynecologic Oncology Group study

OBJECTIVE 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. METHODS 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 40mg/m(2)) and 37 patients were randomized to arm CG (weekly cisplatin 40mg/m(2) and gemcitabine 125mg/m(2)), for six cycles. Six eligible patients were excluded before the beginning of treatment. RESULTS An interim analysis showed superimposable progression-free (PFS) and overall survival (OS), a decision of closing accrual was made. A 3-year PFS was similar in both arms (arm C 65.1% vs. arm CG 71.0%, p=0.71), and a 3-year OS was 74.1% in arm C vs. 85.9% in arm CG (p=0.89), but crossed over at 5years. Grade 2-4 hematological toxicities, including neutropenia (p=0.028) and thrombocytopenia (p=0.001), were more frequent in arm CG than arm C. CONCLUSIONS Despite limitation in power, it suggests that only adding gemcitabine at the CCRT phase does not provide substantially superior results, but treatment toxicities could increase. Further studies are required to determine the role of post-CCRT adjuvant chemotherapy in advanced cervical cancer.

Primary surgery versus primary radiation therapy for FIGO stages I–II small cell carcinoma of the uterine cervix: A retrospective Taiwanese Gynecologic Oncology Group study

OBJECTIVE To evaluate the role of surgery, radiation therapy and chemotherapy in the management of small cell carcinoma of the uterine cervix (SCCC) through a retrospective study of Taiwanese Gynecologic Oncology Group. METHODS We reviewed the medical records and histological files of 144 patients with FIGO stages IA-IIB SCCC treated in 11 main hospitals in Taiwan from 1987 to 2009. RESULTS There were 110 patients receiving primary surgery and 34 primary radiation therapy. Most patients in each group also received chemotherapy as part of primary treatment. A lower loco-regional failure rate was observed in patients who received primary radiation therapy than in those who had primary surgery (6% vs. 27%; P=0.009). The 5-year overall survival (OS) was 89% for 13 surgically treated patients with cervical tumor ≤2cm and no lymphovascular space involvement (LVSI) in whom recurrence was noted in 2 of 4 patients without receiving adjuvant chemotherapy and none in the 9 patients who had chemotherapy. Excluding these 13 patients, primary radiation therapy with at least 5cycles of platinum-based chemotherapy (n=14, including 12 stages IB2-IIB) resulted in a 5-year OS of 78%, better than that of 46% by primary surgery (n=97, including 40 stages IB2-IIB) (P=0.046). CONCLUSIONS None of the 9 patients with cervical tumor ≤2cm and no LVSI showed disease recurrence after primary surgery and adjuvant chemotherapy. For most patients with stages I-II, primary radiation therapy with aggressive chemotherapy was associated with better survival than surgery.

Computed tomography, magnetic resonance imaging and FDG positron emission tomography in the management of vulvar malignancies.

ObjectivesTo prospectively evaluate the value of CT or MRI (CT/MRI) and PET in the management of vulvar malignancies.MethodsAbdominal 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.ResultsTwenty-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.ConclusionsFalse-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.Key Points• 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.

Fertility-preserving treatment in young women with endometrial adenocarcinoma: a long-term cohort study.

Objective Growing evidence suggests that fertility-preserving treatment is feasible for young women with early-stage, low-grade endometrial carcinoma. However, published data on their long-term outcomes and prognostic factors remain scanty. We aimed to investigate the outcomes of young women receiving fertility-preserving treatment. Methods Between 1991 and 2010, the outcomes of young women with grade 1 endometrioid endometrial carcinoma at presumed stage IA (without myometrial invasion) who underwent fertility-preserving treatment of megestrol acetate 160 mg/d with or without other hormonal agents were retrospectively analyzed. Results We identified 37 eligible patients (median age, 32 years; range, 18–40 years). The median follow-up time was 78.6 months (range, 19.1–252.8 months). Complete response (CR) lasting more than 6 months was achieved in 30 (81.1%) women. Responders were significantly younger than nonresponders (P = 0.032). Of the 30 women who had a CR, 15 (50.0%) had disease recurrence. The 5-, 10-, and 15-year cumulative recurrence-free survival rates were 51.0%, 51.0%, and 34.0%, respectively. Notably, those recurred were significantly older (P = 0.003), and the time to CR was significantly longer (P = 0.043) than those without recurrence. One patient developed late recurrences at 156 months, and 2 patients developed ovarian metastasis (6 and 137 months from diagnosis). All the patients are currently alive. Conclusions This study demonstrates the feasibility of high-dose megestrol acetate–based therapy for fertility preservation. The substantial risk of late recurrences highlights the need for long-term follow-up studies of large sample sizes with in-depth tumor and host molecular signatures.

Human papillomavirus 16/18 E7 viral loads predict distant metastasis in oral cavity squamous cell carcinoma

BACKGROUND Human papillomaviruses (HPV) seem to be related to distant metastasis (DM) in advanced oral cavity squamous cell carcinoma (OSCC) patients. OBJECTIVES This study aimed to investigate whether high-risk HPV viral load may predict DM among OSCC patients and stratify patients for risk-adapted treatment. STUDY DESIGN Viral loads of E7 oncogenes for HPV 16/18 were measured by quantitative PCR tests in paraffin-embedded lesional specimens from 312 OSCC of which the HPV genotypes had been determined previously. Multivariable Cox regression analysis was used to identify the independent prognostic factors for 5-year DM and C statistics were further computed. RESULTS By multivariable analysis, high HPV 16 E7 viral load (≥15.0 copies/genome); high HPV 18 E7 viral load (≥15.0 copies/genome); pathological N2 status (pN2); tumor depth ≥11 mm; extracapsular spread (ECS); and level IV/V metastases were independent risk factors for DM. We further identified three prognostic groups. In the high-risk group (level IV/V metastases or high HPV 16/18 E7 viral load plus pN2, tumor depth ≥11 mm, or ECS), the 5-year distant metastasis rate was 74%. In the intermediate-risk group (high HPV 16/18 E7 viral load, pN2, tumor depth ≥11 mm, or ECS), the 5-year DM rate was 17%. Finally, the 5-year DM rate was 1% in the low-risk group (no risk factors). The value of the C statistics was 0.78. CONCLUSIONS Among OSCC patients, high HPV 16/18 E7 viral load identifies a small subgroup of patients at high-risk of 5-year DM and suggest the need for more intensive treatments and follow-up strategies.

Heterogeneity of 18F-FDG PET combined with expression of EGFR may improve the prognostic stratification of advanced oropharyngeal carcinoma

The Angs risk profile (based on p16, smoking and cancer stage) is a well‐known prognostic factor in oropharyngeal squamous cell carcinoma (OPSCC). Whether heterogeneity in 18F‐fluorodeoxyglucose (FDG) positron emission tomographic (PET) images and epidermal growth factor receptor (EGFR) expression could provide additional information on clinical outcomes in advanced‐stage OPSCC was investigated. Patients with stage III–IV OPSCC who completed primary therapy were eligible. Zone‐size nonuniformity (ZSNU) extracted from pretreatment FDG PET scans was used as an index of image heterogeneity. EGFR and p16 expression were examined by immunohistochemistry. Disease‐specific survival (DSS) and overall survival (OS) served as outcome measures. Kaplan–Meier estimates and Cox proportional hazards regression models were used for survival analysis. A bootstrap resampling technique was applied to investigate the stability of outcomes. Finally, a recursive partitioning analysis (RPA)‐based model was constructed. A total of 113 patients were included, of which 28 were p16‐positive. Multivariate analysis identified the Angs profile, EGFR and ZSNU as independent predictors of both DSS and OS. Using RPA, the three risk factors were used to devise a prognostic scoring system that successfully predicted DSS in both p16‐positive and ‐negative cases. The c‐statistic of the prognostic index for DSS was 0.81, a value which was significantly superior to both AJCC stage (0.60) and the Angs risk profile (0.68). In patients showing an Angs high‐risk profile (N = 77), the use of our scoring system clearly identified three distinct prognostic subgroups. It was concluded that a novel index may improve the prognostic stratification of patients with advanced‐stage OPSCC.

Association between multidisciplinary team care approach and survival rates in patients with oral cavity squamous cell carcinoma

The purpose of this study was to investigate whether multidisciplinary team care (MDTC) is associated with outcomes in oral cavity squamous cell carcinoma (SCC).

Randomized, controlled trial of TNF-α antagonist in CTL-mediated severe cutaneous adverse reactions

BACKGROUND. Cytotoxic T lymphocyte–mediated (CTL-mediated) severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), are rare but life-threatening adverse reactions commonly induced by drugs. Although high levels of CTL-associated cytokines, chemokines, or cytotoxic proteins, including TNF-&agr; and granulysin, were observed in SJS-TEN patients in recent studies, the optimal treatment for these diseases remains controversial. We aimed to evaluate the efficacy, safety, and therapeutic mechanism of a TNF-&agr; antagonist in CTL-mediated SCARs. METHODS. We enrolled 96 patients with SJS-TEN in a randomized trial to compare the effects of the TNF-&agr; antagonist etanercept versus traditional corticosteroids. RESULTS. Etanercept improved clinical outcomes in patients with SJS-TEN. Etanercept decreased the SCORTEN-based predicted mortality rate (predicted and observed rates, 17.7% and 8.3%, respectively). Compared with corticosteroids, etanercept further reduced the skin-healing time in moderate-to-severe SJS-TEN patients (median time for skin healing was 14 and 19 days for etanercept and corticosteroids, respectively; P = 0.010), with a lower incidence of gastrointestinal hemorrhage in all SJS-TEN patients (2.6% for etanercept and 18.2% for corticosteroids; P = 0.03). In the therapeutic mechanism study, etanercept decreased the TNF-&agr; and granulysin secretions in blister fluids and plasma (45.7%–62.5% decrease after treatment; all P < 0.05) and increased the Treg population (2-fold percentage increase after treatment; P = 0.002), which was related to mortality in severe SJS-TEN. CONCLUSIONS. The anti–TNF-&agr; biologic agent etanercept serves as an effective alternative for the treatment of CTL-mediated SCARs. TRIAL REGISTRATION. ClinicalTrials.gov NCT01276314. FUNDING. Ministry of Science and Technology of Taiwan.

Prevalence and clinical significance of BRCA1/2 germline and somatic mutations in Taiwanese patients with ovarian cancer

Germline and somatic BRCA1/2 mutations define a subset of patients with ovarian cancer who may benefit from treatment with poly (ADP-ribose) polymerase inhibitors. Unfortunately, data on the frequency of BRCA1/2 germline mutations in Taiwanese patients with ovarian cancer are scarce, with the prevalence of somatic mutations being unknown. We aim to investigate the occurrence of BRCA1/2 mutations in 99 Taiwanese patients with ovarian cancer which included serous (n = 46), endometrioid (n = 24), and clear cell (n = 29) carcinomas. BRCA1/2 mutations were identified using next-generation sequencing of formalin-fixed paraffin-embedded tumor samples. Pathogenic variants (BRCA1: n = 7; BRCA2: n = 6) were detected in 12.1% (12/99) of the study patients. Somatic and germline BRCA1/2 mutation rates in serous ovarian cancer are 4/46 (8.7%) and 8/46 (17%), respectively. All of the pathogenic BRCA1/2 mutations were identified in serous carcinoma samples (12/46; 26.1%). One-third (4/12) of the deleterious BRCA1/2 mutations occurred in tumor tissues only (somatic mutations). All of them coexisted with loss of heterozygosity, resulting in biallelic BRCA inactivation. Five novel pathogenic mutations were identified, including four somatic variants (BRCA1 p.S242fs, BRCA1 p.F989fs, BRCA1 p.G1738fs, and BRCA2 p.D1451fs) and a germline variant (BRCA2 p.E260fs). We also detected additional six novel mutations (three in BRCA1 and three in BRCA2) with pathogenic potentials. We conclude that BRCA1/2 mutations are common in Taiwanese patients with serous ovarian carcinoma and similar to mutation rates in other ethnic groups. The analysis of BRCA1/2 somatic mutations is crucial for guiding therapeutic decisions in ovarian cancer.