Sang-Hue Yen

Concurrent chemoradiotherapy treatment of locally advanced pancreatic cancer: Gemcitabine versus 5-fluorouracil, a randomized controlled study

PURPOSEnTo determine the efficacy and tolerability of gemcitabine (GEM)-concurrent chemoradiotherapy (CCRT) vs. 5-fluorouracil (5-FU) CCRT for locally advanced pancreatic cancer.nnnMETHODS AND MATERIALSnThirty-four patients with locally advanced pancreatic cancer were studied. Eighteen patients were randomized to receive GEM CCRT (600 mg/m(2)/wk for 6 weeks) and 16 patients to receive bolus 5-FU CCRT (500 mg/m(2)/d for 3 days repeated every 2 weeks for 6 weeks). All patients were to receive 3D-CRT 50.4-61.2 Gy at 1.8-Gy/d fractions and GEM (1000 mg/m(2) weekly for 3 weeks repeated every 4 weeks) after RT.nnnRESULTSnThe median survival and median time to progression were 14.5 months and 7.1 months for the GEM CCRT group and 6.7 months and 2.7 months for the 5-FU CCRT group (p = 0.027 and p = 0.019, respectively). The quality-adjusted life month survival time was 11.2 +/- 0.5 months for GEM CCRT and 6.0 +/- 0.3 months for 5-FU CCRT patients (p <0.001). The response rate was 50% (four complete responses and five partial responses) for GEM CCRT and 13% (two partial responses) for 5-FU CCRT (p = 0.005). Pain control was 39% for GEM CCRT and 6% for 5-FU CCRT (p = 0.043). Grade 3-4 neutropenia (34% vs. 19%), thrombocytopenia (0% vs. 7%), nausea (33% vs. 31%), vomiting (17% vs. 19%), hospitalization days per month of survival (7.4 +/- 1.7 days vs. 8.0 +/- 1.3 days), and full dose of RT received (78% vs. 75%) were not significantly different between the GEM CCRT and 5-FU CCRT patients.nnnCONCLUSIONnGEM CCRT appears more effective than 5-FU CCRT for locally advanced pancreatic cancer and has comparable tolerability.

Prognostic Significance of Vascular Endothelial Growth Factor, Basic Fibroblast Growth Factor, and Angiogenin in Patients With Resectable Hepatocellular Carcinoma After Surgery

Background: Hepatocellular carcinoma (HCC) is a hypervascular malignancy. Vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and angiogenin (ANG) are important angiogenic factors of neoangiogenesis. This study investigated the predictive value of serum VEGF, bFGF, and ANG in tumor recurrence, disease-free survival (DFS), and overall survival (OS) in HCC patients.Methods: Preoperative serum VEGF, bFGF, and ANG were measured in 98 patients with resectable HCC and in 15 healthy controls. The median follow-up time was 43 months.Results: Preoperative serum VEGF was increased in patients with resectable HCC compared with healthy controls (P < .05). Increased serum VEGF was correlated with tumor recurrence (P = .001). Univariate analysis showed that serum VEGF, tumor-node-metastasis stage, tumor size and number, macroscopic portal vein invasion, and microscopic vascular invasion were correlated with OS and DFS. Serum bFGF and ANG were not associated with survival. Multivariate analysis showed that serum VEGF was the most significant predictor of DFS (relative risk, 2.35; 95% confidence interval, 1.26–4.39; P = .007) and OS (relative risk, 3.44; 95% confidence interval, 1.81–6.57; P < .001) in HCC patients after surgical resection.Conclusions:Preoperative serum VEGF is a significant independent predictor of tumor recurrence, DFS, and OS in patients with resectable HCC.

Effect of granulocyte-macrophage colony-stimulating factor on oral mucositis in head and neck cancer patients after cisplatin, fluorouracil, and leucovorin chemotherapy.

PURPOSEnTo evaluate prospectively the efficacy of granulocyte-macrophage colony-stimulating factor (GM-CSF) in the reduction of chemotherapy-induced oral mucositis.nnnPATIENTS AND METHODSnTwenty patients with stage IV squamous cell carcinoma of head and neck were studied. Two-cycles (periods) of identical doses of cisplatin, fluorouracil (5-FU), and leucovorin (PFL) chemotherapy with cisplatin 20 mg/m2/d, 5-FU 800 mg/m2/d, leucovorin 90 mg/m2/d by 96-hour continuous intravenous infusion every 3 weeks were given to each patient. After PFL chemotherapy, GM-CSF 4 micrograms/kg subcutaneously from days 5 to 14 or no therapy was given by a randomized self-controlled crossover study design. Oral mucositis was graded with modified Radiation Therapy Oncology Group criteria.nnnRESULTSnIn the first cycle of PFL chemotherapy, GM-CSF significantly reduced the incidence, mean duration, and mean area under the curve (AUC) of severe oral gross mucositis (grade > or = 3) compared with no therapy. These beneficial effects continued into the second cycle of PFL chemotherapy after crossover to no GM-CSF. The incidence of severe mucositis was reduced when GM-CSF was given in the second cycle of PFL. Analysis of variance indicated significant direct GM-CSF treatment effects on the mean AUC of gross/functional scores and duration of moderate gross mucositis (grade > or = 2) over both periods. There was a significant period effect in favor of giving GM-CSF in the first cycle of chemotherapy.nnnCONCLUSIONnGM-CSF can significantly reduce the severity and duration of chemotherapy-induced oral mucositis after PFL chemotherapy.

Germinoma involving the basal ganglia in children

BackgroundGerminoma originating in the basal ganglia is rare, and the majority of reported papers have been from Japan. In a collection of the first 500 cases of primary brain tumors in children in Taipei Veterans General Hospital, six pure germinomas with tissue diagnosis situated in this location.Materials and methodsWe reviewed the clinical features, neuroimaging studies, tumor markers, management, and outcome of these six patients.ResultsAll of them were boys. The median age of onset of symptoms was 9.7xa0years. They uniformly presented with hemiparesis. The average duration of symptoms before surgical management was 1xa0year. One patient had bilateral basal ganglia tumors. Serum β-human chorionic gonadotropin levels was elevated (128xa0mIU/ml) in one patient. Longitudinal neuroimaging studies in four patients clearly showed that the tumor arose as a tiny lesion at the lenticular nucleus. Five patients had cysts within tumors. Five patients received partial, subtotal, to total resection. One patient had stereotactic biopsy of the tumors. Postoperative primary adjuvant therapies included radiotherapy, chemotherapy alone, and combined chemotherapy and radiotherapy. Five patients survived, and one patient died of radiation-induced sarcoma with median follow-up period of 13.7xa0years. Local recurrence was observed in all of three patients after solitary postoperative chemotherapy.ConclusionsThe lenticular nucleus is a significant locus for germinomas and can be bilateral. Although rarely reported in Western countries, it does exist in Taiwan as well. Treatment of germinomas in this specific location is similar to germinoma in other intracranial locations.

Extended focal radiotherapy of 30 Gy alone for intracranial synchronous bifocal germinoma: a single institute experience

ObjectsTo evaluate the disease characteristics and treatment outcomes for patients with intracranial synchronous bifocal germinomas treated with extended focal irradiation alone.MethodsBetween January 1996 and March 2007, seven patients (three males and four females) with intracranial synchronous bifocal germinomas treated at Taipei Veterans General Hospital were reviewed. The median age at diagnosis was 14xa0years (range, 11–28xa0years). Four patients had surgery before radiotherapy. All patients underwent extended focal irradiation encompassing the whole ventricle system with a total radiation dose of 30xa0Gy (2xa0Gy daily). No patient received scheduled systemic chemotherapy before or after radiotherapy. Disease characteristics, treatment outcomes, and the impact of lesion numbers (single vs. bifocal) on survivals were investigated.ResultsWith a median follow-up time of 49xa0months (range, 20–66xa0months), the 2- and 5-year survival rates were both 100%. After treatment, all patients had good performance without recurrence. No severe complication was observed. In comparison, the overall survival (OS, pu2009=u20090.475) and the disease-free survival (DFS, pu2009=u20090.537) rates were not significantly different between bifocal- and single-lesion groups. Lesion numbers did not affect both OS and DFS. In addition, the incidence of neuraxial seeding was not higher in patients with bifocal germinomas as compared to those with single lesion.ConclusionsIntracranial germinomas are extremely radiosensitive. Young patients with synchronous bifocal germinomas could be successfully treated with extended focal 30-Gy radiotherapy alone. The therapeutic advantage using this regimen needs to be further evaluated with larger sample size and longer follow-up time.

Use of a Rich Internet Application Solution to Present Medical Images

Browser with Rich Internet Application (RIA) Web pages could be a powerful user interface for handling sophisticated data and applications. Then the RIA solutions would be a potential method for viewing and manipulating the most data generated in clinical processes, which can accomplish the main functionalities as general picture archiving and communication system (PACS) viewing systems. The aim of this study is to apply the RIA technology to present medical images. Both Digital Imaging and Communications in Medicine (DICOM) and non-DICOM data can be handled by our RIA solutions. Some clinical data that are especially difficult to present using PACS viewing systems, such as ECG waveform, pathology virtual slide microscopic image, and radiotherapy plan, are as well demonstrated. Consequently, clinicians can use browser as a unique interface for acquiring all the clinical data located in different departments and information systems. And the data could be presented appropriately and processed freely by adopting the RIA technologies.

Model-Based Radiation Dose Correction for Yttrium-90 Microsphere Treatment of Liver Tumors With Central Necrosis

PURPOSEnThe objectives of this study were to model and calculate the absorbed fraction ϕ of energy emitted from yttrium-90 ((90)Y) microsphere treatment of necrotic liver tumors.nnnMETHODS AND MATERIALSnThe tumor necrosis model was proposed for the calculation of ϕ over the spherical shell region. Two approaches, the semianalytic method and the probabilistic method, were adopted. In the former method, the range--energy relationship and the sampling of electron paths were applied to calculate the energy deposition within the target region, using the straight-ahead and continuous-slowing-down approximation (CSDA) method. In the latter method, the Monte Carlo PENELOPE code was used to verify results from the first method.nnnRESULTSnThe fraction of energy, ϕ, absorbed from (90)Y by 1-cm thickness of tumor shell from microsphere distribution by CSDA with complete beta spectrum was 0.832 ± 0.001 and 0.833 ± 0.001 for smaller (r(T) = 5 cm) and larger (r(T) = 10 cm) tumors (where r is the radii of the tumor [T] and necrosis [N]). The fraction absorbed depended mainly on the thickness of the tumor necrosis configuration, rather than on tumor necrosis size. The maximal absorbed fraction φ that occurred in tumors without central necrosis for each size of tumor was different: 0.950 ± 0.000, and 0.975 ± 0.000 for smaller (r(T) = 5 cm) and larger (r(T) = 10 cm) tumors, respectively (p < 0.0001).nnnCONCLUSIONSnThe tumor necrosis model was developed for dose calculation of (90)Y microsphere treatment of hepatic tumors with central necrosis. With this model, important information is provided regarding the absorbed fraction applicable to clinical (90)Y microsphere treatment.

Head and Neck Nodal Station Images: Guidance for Three-dimensional Radiation Therapy Treatment Planning

When we use radiation to treat cancer patients, the irradiated volume usually encloses the detectable tumor and any metastatic areas that are thought to be at risk. Usually, in three-dimensional (3D) radiation therapy, we need to define the clinical target volume (CTV), which identifies the areas suspected of containing microscopic metastasis. We can use a set of computed tomographic (CT) images to define these suspected areas, which we relate to nodal station distributions. The traditional method uses special anatomic landmarks for such definition. This lymph node image guidance method uses a set of CT images to show the relevant nodal stations and find the correlation between the suspected areas and the lymphatic pathways. First, we used CT images from head and neck cancer patients. Then, we designed a program to delineate the regional lymphatic areas in order to distinguish the position of all the major lymph nodes in the head and neck region. These lymph nodes were then used to assist the oncologist in developing treatment references. Finally, we established a database management system to determine the relationships between different lesions and lymph nodes, as well as correlations, with metastatic pathways. Defining these relationships on the CT images provided oncologists specific information that could be used to define the CTV more precisely for 3D radiation therapy.n

Comparison of Altered Fractionation and Conventional Radiotherapy for Primary Central Nervous System Lymphoma

Purpose: To assess the treatment outcomes of primary central nervous lymphoma (PCNSL) treated with different radiotherapy (RT) fractionation strategies (conventional fractionation vs. altered fractionated radiotherapy) with or without systemic chemotherapy. Materials and Methods: Between January 1990 and December 2004, 44 patients with PCNSL (pathological or clinical) treated with curative radiotherapy at Taipei Veterans General Hospital were reviewed. There were 29 males and 15 females, with a median age of 64 (range, 21-80). Patients were retrospectively classified into 4 groups: 1) conventional fractionated radiotherapy alone (n=15); 2) combined conventional fractionated radiotherapy with chemotherapy (n=5); 3) altered fractionated radiotherapy (1.2-1.5 Gy per fraction, twice daily) alone (n=17); and 4) altered fractionated radiotherapy with chemotherapy (n=7). All chemotherapy, mostly (n=10) methotrexate (MTX) based regimens, were given before radiotherapy. Overall survival (OS) and progression-free survival (PFS) were estimated using Kaplan-Meier method and subgroups were compared with log-rank test. Results: The median follow-up duration was 24.3 months (range, 2.7-83.1 months). Of the evaluable 39 patients, 32 patients (82%) obtained complete response and 5 patients (13%) had partial response. The median PFS was 18.9 months (95% confidence interval [CI], 10-27) with estimated 1-, 2- and 5-year PFS of 61%, 40% and 10%, respectively. The median OS was 25.8 months (95% CI, 16-36) with estimated 1-, 2- and 5-year survival rate of 75%, 54% and 15%, respectively. There was no significant difference in the OS and PFS between groups using conventional RT and altered fractionated RT regardless of chemotherapy (p=0.28 and 0.14, respectively). Age, Karnofsky performance status (KPS) and administration of chemotherapy were important prognostic factors in univariate analysis, but only age at diagnosis remained significant in multivariate model. Median survival was 35.9 months in patients younger than 64 and only 18.9 months in those aged 64 or older (p= 0.011). Patients with KPS ≥70 had a median survival of 32.2 months, which was longer than 13.1 months of patients with KPS ＜ 70 (p= 0.016). Conclusions: Altered fractionated radiotherapy is not beneficial in improving survivals of PCNSL. Age and performance status are most important prognostic predictors in PCNSL and should be taken into account in the selection of treatment modalities.