Biomedical subjects

Ching-Yeh Hsiung

Publications and source records attributed to Ching-Yeh Hsiung.

13 recordsLinked to original sources

PubMed2007

Intensity-modulated or conformal radiotherapy improves the quality of life of patients with nasopharyngeal carcinoma: comparisons of four radiotherapy techniques.

BACKGROUND: It was reported previously that the dosimetric superiority of conformal radiotherapy (RT), either 3-dimensional conformal RT (3D-CRT) or intensity-modulated RT (IMRT), over conventional 2D-RT translated into clinical benefits for patients with nasopharyngeal carcinoma (NPC). In this study, the authors compared quality-of-life (QOL) outcomes of NPC survivors who received treatment with 1 of 4 different RT techniques at a single institute during different periods. METHODS: The authors analyzed QOL data of from 237 patients with NPC who were cancer free for 2 or 3 years when their QOL was assessed. The study population included 152 patients who received conventional RT (2D-RT, 61 patients; 2D-RT plus 3D-CRT boost, 91 patients) and 85 patients who received conformal RT (3D-CRT, 33 patients; IMRT, 52 patients). The European Organization for the Research and Treatment of Cancer (EORTC) Core QOL questionnaire and the EORTC Head and Neck QOL questionnaire were completed. RESULTS: Compared with patients who received with conventional RT, patients who received conformal RT had both statistically (P < .05) and clinically (a difference in mean scores >or=10 points) significant improvements in the scales of global QOL, pain, appetite loss, senses, speech, social eating, teeth, opening mouth, xerostomia, sticky saliva, and feeling ill. No significant difference was observed in any of the scales that compared 2D-RT with 2D-RT plus 3D-CRT boost or that compared 3D-CRT with IMRT. Survivors who received conformal RT had a 2.01-fold higher probability (odds ratio [OR], 2.01; 95% confidence interval [95% CI], 1.19-3.68) of reporting good global QOL and a 2.70-fold lower probability (OR, 0.37; 95% CI, 0.20-0.66) of reporting a high level of xerostomia than survivors who received conventional RT. CONCLUSIONS: Conformal RT substantially improved head and neck-related symptoms and broad aspects of QOL for survivors of NPC.

Adult↗

PubMed2006

Immunohistochemical expression of p16INK4A, Ki-67, and Mcm2 proteins in gastrointestinal stromal tumors: prognostic implications and correlations with risk stratification of NIH consensus criteria.

BACKGROUND: Inactivation of p16(INK4A) promotes G1/S progression of cell cycle. Minichromosome maintenance protein-2 (Mcm2), a novel cell proliferation marker, is known to better correlate with clinical outcomes than Ki-67 in many carcinomas. Since gastrointestinal stromal tumors (GISTs) sometimes remains challenging in prognostication, we analyzed the utility of these three markers in GISTs. METHODS: Immunohistochemistry was performed in tissue microarrays of 277 primary GISTs and correlated with NIH consensus criteria and clinical outcomes. RESULTS: The increment of NIH risk levels significantly correlated with increasing labeling indices (LI) of both Ki-67 (P <.001) and Mcm2 (P <.001) and loss of p16(INK4A) expression (P <.035). However, the latter aberration did occur in 23% of very low/low-risk GISTs. The relationship between Mcm2 and Ki-67 LIs could be modeled as linear (P <.001, r = 0.697), while Mcm2 LI was considerably higher (P <.001) with a stepwise escalation related to risk levels. Ki-67 LI >5% (P <.0001) and Mcm2 LI >10% (P <.0001) were strongly predictive of inferior disease-specific survival (DSS), while aberrant loss of p16(INK4A) only reached a trend (P = .0954). In multivariate analyses, independent adverse factors of DSS were high-risk category (RR = 16.93, P <.0001), metastatic disease (RR = 4.12, P = .0015), Ki-67 LI >5% (RR = 3.55, P = .001), and presence of epithelioid histology (RR = 2.17, P = .0308). CONCLUSIONS: Prognostic efficacy of NIH consensus criteria is substantiated. P16(INK4A) deregulation can occur early in GIST tumorigenesis and marginally correlates with patient survival. Despite Ki-67 LI being an independent prognosticator, simultaneous detection of Mcm2 is recommended as a prognostic adjunct of GISTs, given its better sensitivity and stepwise escalation with increasing risk levels.

Adult↗

PubMed2006

Multivariate analyses of locoregional recurrences and skin complications after postmastectomy radiotherapy using electrons or photons.

PURPOSE: We retrospectively analyzed factors of locoregional (LR) recurrence and skin complications in patients after postmastectomy radiotherapy (PMRT). METHODS AND MATERIALS: From January 1988 to December 1999, a total of 246 women with Stage II and III breast cancer received PMRT. Doses of 46 to 52.2 Gy/23 to 29 fractions were delivered to the chest wall (CW) and peripheral lymphatic drainage with 12 to 15 MeV single-portal electrons or 6MV photons. Of the patients, 84 patients received an additional 6 to 20 Gy boost to the surgical scar using 9 MeV electrons. We used the Cox regression model for multivariate analyses of CW, supraclavicular nodes (SCN), and LR recurrence. RESULTS: N3 stage (positive nodes >9) (p = 0.003) and diabetes (p = 0.004) were independent factors of CW recurrence. Analysis of ipsilateral SCN recurrence showed that N3 stage (p < 0.001) and electrons (p = 0.006) were independent factors. For LR recurrence, N3 (p < 0.001), T3 to T4 (p = 0.033) and electrons (p = 0.003) were significant factors. Analysis of skin telangiectasia revealed that electrons (p < 0.001) and surgical scar boost (p = 0.003) were independent factors. CONCLUSIONS: Photons are superior to single-portal electrons in patients receiving postmastectomy radiotherapy because of better locoregional control and less skin telangiectasia. In patients in whom the number of positive axillary nodes is >9, more aggressive treatment may be considered for better locoregional control.

Breast Neoplasms↗

PubMed2006

Parotid-sparing intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma: preserved parotid function after IMRT on quantitative salivary scintigraphy, and comparison with historical data after conventional radiotherapy.

PURPOSE: To evaluate the parotid function after parotid-sparing intensity-modulated radiotherapy (IMRT) in patients with nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: From March 2003 to May 2004, 16 patients with nonmetastatic NPC underwent parotid-sparing IMRT. Eight of these patients had Stage III or IV NPC based on the 1997 American Joint Committee on Cancer staging system. The post-IMRT parotid function was evaluated by quantitative salivary scintigraphy and represented by the maximal excretion ratio (MER) of the parotid gland after sialogogue stimulation. The parotid function of 16 NPC patients who were previously treated with conventional radiotherapy was reviewed as the historical control. RESULTS: In the parotid-sparing IMRT group, all 16 patients were alive and without cancer at the end of follow-up period (median, 24.2 months). The mean parotid MER was 53.5% before radiotherapy, 10.7% at 1 month post-IMRT, and 23.3% at 9 months post-IMRT. In the conventional radiotherapy group, the mean parotid MER was 0.6% at 6 to 12 months postradiotherapy. The difference was statistically significant (23.3% vs. 0.6%, p<0.001, Mann-Whitney test). In the IMRT group, the mean parotid doses ranged from 33.2 Gy to 58.8 Gy (average, 43.9 Gy). The correlation between the mean parotid dose and the percentage decrease of parotid MER at 9 months post-IMRT (dMER) was statically significant (p=0.008, Pearson correlation). CONCLUSIONS: Although the mean parotid doses are relatively high, the significant preservation of parotid function is achieved with IMRT for NPC patients. The significant correlation between mean parotid dose and parotid dMER demonstrates the dose-function relationship of the parotid gland.

Dose-Response Relationship, Radiation↗

PubMed2006

Prognostic factors of myxofibrosarcomas: implications of margin status, tumor necrosis, and mitotic rate on survival.

BACKGROUND: Myxofibrosarcomas (MFS) are characterized by tumor progression with increased metastases after local recurrences (LR). Few series had appropriately addressed what parameters independently affect prognosis. METHODS: Seventy primary localized MFS were analyzed for local recurrence-free survival (LRFS), metastasis-free survival (MeFS), and disease-specific survival (DSS). Follow-up was obtained in 61 cases. RESULTS: Thirty-eight males and 32 females had primary tumors ranging from 1.5 to 24 cm. Thirty and 40 tumors were superficial and deep, respectively, with 26 cases (38%) having positive margins. The 5-year LRFS-, MeFS-, and DSS-rates were 30%, 60%, and 73%. Positive margins (P = 0.0003) were the only inferior LRFS predictor. High grade (FNCLCC 2 and 3) was a negative factor of both MeFS (P = 0.0078) and DSS (P = 0.0174), and high stage (AJCC stage 3) was predictive of MeFS (P = 0.0470). However, both grading and staging were not prognostically independent. In multivariate analyses, mitoses >or=20/10 HPF (P = 0.0009, RR = 9.71) and positive margins (P = 0.0203, RR = 4.27) were independent adverse DSS predictor. However, tumor necrosis >or=10% (P = 0.0092, RR = 3.91) independently correlated with worse MeFS, together with mitoses >or=20/10 HPF (P = 0.0176, RR = 3.80) and positive margins (P = 0.0121, RR = 3.41). CONCLUSIONS: Margin status and histologic property both affect the prognosis of MFS. The former correlates with improved LRFS and translates into final survival benefits.

Adolescent↗

PubMed2006

Skp2 overexpression is highly representative of intrinsic biological aggressiveness and independently associated with poor prognosis in primary localized myxofibrosarcomas.

PURPOSE: Two SCF(Skp2) ubiquitin ligase-related proteins, Skp2 and cyclin-dependent kinase subunit 1 (Cks1), are involved in posttranscriptional degradation of p27(Kip1) tumor suppressor. We analyzed the prognostic utility of p27(Kip1) and its interacting cell cycle regulators in myxofibrosarcomas. EXPERIMENTAL DESIGN: Clinicopathologic features and tissue microarray-based immunohistochemical expression of p27(Kip1), Skp2, Cks1, cyclin E, cyclin A, Ki-67, and minichromosome maintenance protein 2 (Mcm2) were assessed in 70 primary myxofibrosarcomas and correlated with clinical outcomes. Skp2 mRNA expression and the relationship between Skp2 and p27(Kip1) proteins were examined in six cases by semiquantitative reverse transcription-PCR and Western blotting, respectively. RESULTS: High indices of Skp2 (> or =10%), cyclin A (> or =10%), and Mcm2 (> or =50%) were adverse prognosticators at the univariate level. Furthermore, co-overexpression of Skp2 and cyclin A identified highly lethal cases in the entire cohort [P < 0.0001 for disease-specific survival (DSS), P = 0.0004 for overall survival (OS)] and the lower-grade subset (Fédération Nationale des Centres de Lutte Contre le Cancer grade 1 and 2; P = 0.0006 for DSS, P = 0.0093 for OS). In multivariate analyses, Skp2 overexpression overshadowed most intrinsic clinicopathologic factors and independently correlated with worse metastasis-free survival (P = 0.0012), DSS (P = 0.0234), and OS (P = 0.0056). Notably, positive margins independently predicted inferior local recurrence-free survival (P = 0.0012) and also negatively affected metastasis-free survival (P = 0.0471), DSS (P = 0.0152), and OS (P = 0.0173). Reverse transcription-PCR showed up-regulation of Skp2 mRNA in four cases and Western blotting displayed a matched expression pattern of Skp2. CONCLUSIONS: Margin status and intrinsic property of myxofibrosarcomas both affect patient survival. Skp2 overexpression is highly representative of the biological aggressiveness of myxofibrosarcomas and plays an important prognostic role.

Adolescent↗

PubMed2006

Primary lymphoepithelioma-like carcinoma of minor salivary gland: a case report with immunohistochemical and in situ hybridization studies.

BACKGROUND: Lymphoepithelioma-like carcinomas (LEC) of salivary glands represent rare epithelial malignancies, with most cases affecting the parotid gland. To our knowledge, there was only one LEC arising from the minor salivary gland described in the English-language literature. METHODS: We report the second LEC of the minor salivary gland in the buccal area of a 50-year-old Taiwanese woman, who underwent surgical resection and adjuvant radiotherapy and remained alive and well after 120 months of follow-up. Histologically, irregular tumor nests of undifferentiated epithelial cells with syncytial cell boundaries were found embedded within rich lymphoplasmacytic stroma. The tumor cells also showed strong c-KIT expression and evidence of Epstein-Barr virus (EBV) infection. CONCLUSIONS: Our case suggests potential pathogenic implications of both c-KIT and EBV in LEC of the minor salivary gland that can be cured by the combination of surgery and radiotherapy and has a very favorable long-term prognosis.

Biomarkers, Tumor↗

PubMed2005

Changing quality of life in patients with advanced head and neck cancer after primary radiotherapy or chemoradiation.

OBJECTIVE: The purpose of this study was to investigate the longitudinal changes in quality of life (QoL) for patients with advanced stage (stage III or IV) head and neck squamous cell carcinoma (HNSCC) following primary radiotherapy (RT) or concomitant chemoradiotherapy. METHODS: From January 2001 to January 2003, 149 patients with advanced HNSCC were enrolled. The data pertaining to their QoL were collected using the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) and the EORTC Head and Neck Module (QLQ-H&N35) before and 1 year after RT. RESULTS: Sixty-eight (46%) patients dropped out during the study period. Thirty-nine (57%) of them died of cancer. Those who were older, stage IV, treated by RT alone, or had worse pretreatment EORTC QoL scales were significantly more likely to drop out. For those completing the study, only the problems of swallowing, dry mouth, and sticky saliva were found to become more serious with both statistical (p < 0.05) and clinical (difference >10 points) significance 1 year after RT. Those subjects with cancer at the hypopharynx/larynx had a 3.3-fold higher probability to report an improvement in global QoL (95% confidence interval, CI: 1.11-6.82) than those with cancer at the oral cavity/oropharynx. Those alive without cancer 1 year after RT had a 3.6-fold higher probability to report an improvement in global QoL (95% CI: 1.32-7.13) than those alive with cancer. CONCLUSION: The study showed a high dropout rate in this longitudinal QoL study for patients with advanced HNSCC. Pretreatment cancer sites and living with cancer or not after treatment significantly affected the change in global QoL 1 year after RT.

Adult↗

PubMed2005

Intensity-modulated radiotherapy as the boost or salvage treatment of nasopharyngeal carcinoma: the appropriate parameters in the inverse planning and the effect of patient's anatomic factors on the planning results.

The current study demonstrates that the large increase in normal tissue penalty often degrades target dose uniformity without a concomitant large improvement in normal tissue dose, especially in anatomically unfavorable patients. The excessively large normal tissue penalties do not improve treatment plans for patients having unfavorable geometry.

Carcinoma↗

PubMed2005

The degree and time-course assessment of radiation-induced trismus occurring after radiotherapy for nasopharyngeal cancer.

OBJECTIVES/HYPOTHESIS: The objectives were to measure the degree of trismus induced after radiation therapy for nasopharyngeal cancer and assess its progress over time. STUDY DESIGN: A prospective, single-armed measurement study with long-term follow-up. METHODS: Seventeen patients with nasopharyngeal cancer treated between 1997 and 1999 were studied. Patients were given radiation therapy with bilateral parallel-opposing ports of 45 Gy, 25 fractions, then with a reduced volume to 68.4 to 70.2 Gy. The end point was the degree of trismus, which was measured by serial changes of the maximal interincisal distance (MID) at various specified time points before, during, and after radiation therapy. RESULTS: During the 9 weeks of radiation therapy there was no significant change of MID (normalized MID ranged from 99.8% to 97%). The rate of decrease during this period was 1.3% per month. After radiation therapy there was a rapid decrease of MID between 1 and 9 months (normalized MID values at 1 and 9 mo were 95.5% +/- 3.1% and 74.2% +/- 5.7%, respectively). The rate of decrease during this period was dramatic (2.4%/mo). One year after radiation therapy, the rate of decrease became slower but was still measurable (0.2%/mo for the period from 12 to 24 mo). For the period from 24 to 48 months. the rate dropped to 0.1% per month. By the end of 48 months, normalized MID was 67.8% +/- 7.6%. CONCLUSION: By means of measurement over a period of time, it was found that patients with nasopharyngeal cancer had a mean decrease in initial interincisal distance of 32% at 4 years after radiotherapy. The trismus process evolved at different rates. It was rapid at 1 to 9 months after radiation therapy, then became slower and protracted over later years.

Adult↗

PubMed2004

Quality of life as a survival predictor for esophageal squamous cell carcinoma treated with radiotherapy.

PURPOSE: Accumulating reports suggest that quality of life (QOL) may predict survival in cancer patients. In this study, we longitudinally investigated whether the QOL data assessed before, during, and after treatment are prognostic for the survival of patients with esophageal squamous cell carcinoma treated with primary radiotherapy (RT). METHODS AND MATERIALS: A total of 110 consecutive new esophageal squamous cell carcinoma patients treated with primary RT were studied. The European Organization for the Research and Treatment of Cancer questionnaire QLQ-C30 (in the Taiwan Chinese version) plus the scales concerning dysphagia and odynophagia were completed before, during, and 2 months after RT. Cox proportional hazards models were used to analyze the impact of clinical and QOL variables on survival. RESULTS: A clinical model that included clinical and sociodemographic variables to predict survival using multivariate analysis revealed weight loss, American Joint Committee on Cancer stage, and radiation dose to be statistically significant survival predictors. For QOL scores before RT, physical functioning was the most significant survival predictor. The 2-year survival rate was 30% for patients with a physical functioning score of > or =80.0 compared with a survival rate of 20% for those with a score of <80.0. The QOL scores during RT did not significantly correlate with survival. Of the QOL scores 2 months after RT, the dysphagia symptom scale was the most significant survival predictor. Improvement in dysphagia was observed in 43.0% of patients during RT and in 48.4% of patients 2 months after RT. A dysphagia-free status was found in 35.5% of patients 2 months after RT. The 2-year survival rate was 54.5% for patients without dysphagia 2 months after RT compared with 14.3% for those with dysphagia (p <0.001). CONCLUSION: The data provide evidence to support the correlation of patient-reported QOL scores with survival. Pretreatment physical functioning might be a surrogate marker of an unrecognized biologic prognostic factor. The poor survival outcome for patients with persistent dysphagia after treatment implies that local control remains the main issue to overcome in treating esophageal cancer with RT.

Aged↗

PubMed2002

Evaluation of concave dose distributions created using an inverse planning system.

PURPOSE: To evaluate and develop optimum inverse treatment planning strategies for the treatment of concave targets adjacent to normal tissue structures. METHODS AND MATERIALS: Optimized dose distributions were designed using an idealized geometry consisting of a cylindrical phantom with a concave kidney-shaped target (PTV) and cylindrical normal tissues (NT) placed 5-13 mm from the target. Targets with radii of curvature from 1 to 2.75 cm were paired with normal tissues with radii between 0.5 and 2.25 cm. The target was constrained to a prescription dose of 100% and minimum and maximum doses of 95% and 105% with relative penalties of 25. Maximum dose constraint parameters for the NT varied from 10% to 70% with penalties from 10 to 1000. Plans were evaluated using the PTV uniformity index (PTV D(max)/PTV D(95)) and maximum normal tissue doses (NT D(max)/PTV D(95)). RESULTS: In nearly all situations, the achievable PTV uniformity index and the maximum NT dose exceeded the corresponding constraints. This was particularly true for small PTV-NT separations (5-8 mm) or strict NT dose constraints (10%-30%), where the achievable doses differed from the requested by 30% or more. The same constraint parameters applied to different PTV-NT separations yielded different dose distributions. For most geometries, a range of constraints could be identified that would lead to acceptable plans. The optimization results were fairly independent of beam energy and radius of curvature, but improved as the number of beams increased, particularly for small PTV-NT separations or strict dose constraints. CONCLUSION: Optimized dose distributions are strongly affected by both the constraint parameters and target-normal tissue geometry. Standard site-specific constraint templates can serve as a starting point for optimization, but the final constraints must be determined iteratively for individual patients. A strategy whereby NT constraints and penalties are modified until the highest acceptable PTV uniformity index is achieved is discussed. This strategy can be used, in simple patient geometries, to ensure the lowest possible normal tissue dose. Strategies for setting the optimum dose constraints and penalties may vary for different optimization algorithms and objective functions. Increasing the number of beams can significantly improve normal tissue dose and target uniformity in situations where the PTV-NT separation is small or the normal tissue dose limits are severe. Setting unrealistically severe constraints in such situations often results in dose distributions that are inferior to plans achieved with more lenient constraints.

Algorithms↗

PubMed2002

Intensity-modulated radiotherapy versus conventional three-dimensional conformal radiotherapy for boost or salvage treatment of nasopharyngeal carcinoma.

PURPOSE: To compare intensity-modulated radiotherapy (IMRT) and conventional three-dimensional conformal radiotherapy (3D-CRT) for the boost treatment of new-onset nasopharyngeal carcinoma (NPC) or the salvage treatment of locally recurrent NPC. METHODS AND MATERIALS: Between January 14 and February 23, 2000, 5-field 3D-CRT treatment plans were generated for 14 consecutive NPC patients using the ADAC Pinnacle planning system in Chang Gung Memorial Hospital, Kaohsiung, Taiwan. The planning data of these patients were later transferred to Memorial Sloan-Kettering Cancer Center, where new IMRT plans, also using 5-7 radiation fields were created for each patient using an inverse treatment planning system. The IMRT and 3D-CRT plans were compared for all 14 patients. The relationship between the anatomic shapes and locations of targets and the results of different plans were studied. RESULTS: Target doses were more homogeneous in IMRT plans. The average maximal brainstem dose (D(05), the dose received by 5% of the brainstem volume) decreased from 30.9% of the prescription dose with 3D-CRT to 15.3% and 14.7% with 5- and 7-field IMRT, respectively (p = 0.004 and 0.003, respectively, compared with 3D-CRT, paired Student's t test). Five anatomic factors were found that predicted greater benefits with IMRT. These factors were (1) vertical length of target >7 cm, (2) minimal distance between target and brainstem <0.1 cm, (3) maximal AP overlap of target and brainstem >0.6 cm, (4) maximal AP overlap of target and spinal cord >1 cm, and (5) vertical overlap of target and eyes >0 cm. For the 7 patients with at least 1 of these 5 anatomic factors, the benefits achieved by IMRT planning would have been greater than the benefits for the other 7 patients (p = 0.005, Fisher's exact test). CONCLUSION: For boost or salvage treatment of NPC, lower normal tissue doses and more homogeneous target doses were achieved with IMRT plans. For NPC patients with at least 1 of the 5 anatomic factors, IMRT is highly recommended.

Algorithms↗