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Anne W M Lee,
Stewart Y Tung, Roger K C Ngan,
Rick Chappell,
Daniel T T Chua,
T X Lu,
Lillian Siu,
Terence Tan,
L K Chan,
W T Ng,
T W Leung,
Y T Fu,
Gordon K H Au,
C Zhao,
Brian O'Sullivan,
E H Tan,
W H Lau
[show abstract]
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ABSTRACT: The current standard treatment for locoregionally advanced nasopharyngeal carcinoma (NPC) was conventional-fractionation radiotherapy plus concurrent-adjuvant chemotherapy as recommended by the Intergroup-0099 Study. This combined analysis of the NPC-9901 and the NPC-9902 Trials aims to provide more comprehensive data to evaluate the efficacy of the Intergroup-0099 regimen and the contributing factors.
Eligible patients with stage III-IVB non-keratinizing NPC were randomly assigned to radiotherapy-alone (RT(i) group: 218 patients) or chemoradiotherapy (CRT(i) group: 223 patients) using cisplatin (100mg/m(2)) for three cycles in concurrence with radiotherapy, followed by cisplatin (80 mg/m(2)) plus fluorouracil (1000 mg/m(2)/day for 4 days) for three cycles. The median follow-up was 6.1 years.
Comparison by intention-to-treat showed that the CRT(i) group achieved significant improvement in overall failure-free rate (FFR), locoregional-FFR and cancer-specific survival (p ≤ 0.019); but the improvements for distant-FFR and overall survival (OS) were statistically insignificant (p ≥ 0.14). Further exploratory studies based on actual treatment showed that an additional improvement achieved was a significant gain in OS (CRT(a) versus RT(a) group: 72% versus 63% at 5-year, p=0.037). Multivariate analyses showed that the dose of cisplatin during the concurrent phase had significant impact on locoregional-FFR and OS, while that of fluorouracil during the adjuvant phase was significant for distant-FFR. The 5-year locoregional-FFR for patients who received 0-1, 2 and 3 concurrent cycles were 79%, 88% and 88%, respectively; the corresponding distant-FFR by adjuvant cycles were 68%, 78% and 77%, respectively.
Our results support the current practice of adding concurrent cisplatin plus adjuvant cisplatin-fluorouracil to radiotherapy for treating patients with locoregionally advanced NPC. The concurrent phase is important for locoregional control and survival, cisplatin 200mg/m(2) in two concurrent cycles might be adequate. Additional chemotherapy using fluorouracil-containing combination contributed to improving distant control.
European journal of cancer (Oxford, England: 1990) 11/2010; 47(5):656-66. · 4.12 Impact Factor
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Anne W M Lee,
Stewart Y Tung,
Daniel T T Chua, Roger K C Ngan,
Rick Chappell,
Raymond Tung,
Lillian Siu,
W T Ng,
W K Sze,
Gordon K H Au,
Stephen C K Law,
Brian O'Sullivan,
T K Yau,
T W Leung,
Joseph S K Au,
W M Sze,
C W Choi,
K K Fung,
Joseph T Lau,
W H Lau
[show abstract]
[hide abstract]
ABSTRACT: Current practice of adding concurrent-adjuvant chemotherapy to radiotherapy (CRT) for treating advanced nasopharyngeal carcinoma is based on the Intergroup-0099 Study published in 1998. However, the outcome for the radiotherapy-alone (RT) group in that trial was substantially poorer than those in other trials, and there were no data on late toxicities. Verification of the long-term therapeutic index of this regimen is needed.
Patients with nonkeratinizing nasopharyngeal carcinoma staged T1-4N2-3M0 were randomly assigned to RT (176 patients) or to CRT (172 patients) using cisplatin (100 mg/m(2)) every 3 weeks for three cycles in concurrence with radiotherapy, followed by cisplatin (80 mg/m(2)) plus fluorouracil (1000 mg per m(2) per day for 4 days) every 4 weeks for three cycles. Primary endpoints included overall failure-free rate (FFR) (the time to first failure at any site) and progression-free survival. Secondary endpoints included overall survival, locoregional FFR, distant FFR, and acute and late toxicity rates. All statistical tests were two-sided.
The two treatment groups were well balanced in all patient characteristics, tumor factors, and radiotherapy parameters. Adding chemotherapy statistically significantly improved the 5-year FFR (CRT vs RT: 67% vs 55%; P = .014) and 5-year progression-free survival (CRT vs RT: 62% vs 53%; P = .035). Cumulative incidence of acute toxicity increased with chemotherapy by 30% (CRT vs RT: 83% vs 53%; P < .001), but the 5-year late toxicity rate did not increase statistically significantly (CRT vs RT: 30% vs 24%; P = .30). Deaths because of disease progression were reduced statistically significantly by 14% (CRT vs RT: 38% vs 24%; P = .008), but 5-year overall survival was similar (CRT vs RT: 68% vs 64%; P = .22; hazard ratio of CRT = 0.81, 95% confidence interval = 0.58 to 1.13) because deaths due to toxicity or incidental causes increased by 7% (CRT vs RT: 1.7% vs 0, and 8.1% vs 3.4%, respectively; P = .015).
Adding concurrent-adjuvant chemotherapy statistically significantly reduced failure and cancer-specific deaths when compared with radiotherapy alone. Although there was no statistically significant increase in major late toxicity, increase in noncancer deaths narrowed the resultant gain in overall survival.
CancerSpectrum Knowledge Environment 08/2010; 102(15):1188-98. · 14.07 Impact Factor
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American Journal of Hematology 01/2010; 85(5):362 - 363. · 4.67 Impact Factor
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Artificial Intelligence in Medicine. 01/2010; 48:119-127.
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American Journal of Hematology 01/2010; 85(5):362-3. · 4.67 Impact Factor
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[show abstract]
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ABSTRACT: To develop regulatory network to explore and model the regulatory relationships of protein biomarkers and classify different disease groups.
Regulatory network is constructed to be a hopfield-like network with nodes representing biomarkers and directional connections to be regulations in between. The input to the network is the measured expression levels of biomarkers, and the output is the summation of regulatory strengths from other biomarkers. The network is optimized towards minimizing the energy function that is defined as the measure of the disagreement between the input and output of the network. To simulate more complicated regulations, a sigmoid kernel function is imposed on each node to construct a non-linear regulatory network.
Two datasets have been used as test beds, one dataset includes patients of nasopharyngeal carcinoma with different responses to chemotherapy drug, and the other consists of patients of severe acute respiratory syndrome, influenza, and control normals. The regulatory networks among protein biomarkers were reconstructed for different disease conditions in each dataset. We demonstrated our methods have better classification capability when comparing with conventional methods including Fisher linear discriminant (FLD), K-nearest neighborhood (KNN), linear support vector machines (linSVM) and radial basis function based support vector machines (rbfSVM).
The derived networks can effectively capture the unique regulatory patterns of protein markers associated with different patient groups and hence can be used for disease classification. The discovered regulation relationships can potentially provide insights to revealing the molecular signaling pathways. In this paper, a novel technique of regulatory network is proposed on purpose of modeling biomarker regulations and classifying different disease groups. The network is composed of a certain number of nodes that are directionally connected in between in which nodes denote predictors and connections to be the regulation relationship. The network is optimized towards minimizing its energy function with biomarker expression data acquired from a specific patient group, thus the optimized network can model the regulatory relationship of biomarkers under the same circumstance. To simulate more complicated regulations, a sigmoid kernel function is imposed on each node to construct a non-linear regulatory network. The regulatory network can extract unique features of each disease condition, thus one immediate application of regulatory network is to classifying different diseases. We demonstrated that regulatory network is capable of performing disease classification through comparing with conventional methods including FLD, KNN, linSVM and rbfSVM on two protein datasets. We believe our method is promising in mining knowledge of protein regulations and be powerful for disease classification.
Artificial intelligence in medicine 12/2009; 48(2-3):119-27. · 1.65 Impact Factor
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Proceedings of the 2008 International Conference on BioMedical Engineering and Informatics, BMEI 2008, May 28-30, 2008, Sanya, Hainan, China - Volume 1; 01/2008
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William C S Cho,
Timothy T C Yip, Roger K C Ngan,
Tai-Tung Yip,
Vladimir N Podust,
Christine Yip,
Harry H Y Yiu,
Victor Yip,
Wai-Wai Cheng,
Victor W S Ma,
Stephen C K Law
[show abstract]
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ABSTRACT: We previously used ProteinChip array profiling analysis to discover a serum biomarker associated with nasopharyngeal carcinoma (NPC). In this study, we used the same method to examine other biomarkers associated with NPC and response to chemotherapy (CT) in NPC patients.
We performed ProteinChip array analysis in 209 serum samples from 66 relapsed patients before and after salvage CT with gemcitabine and cisplatin or etoposide and cisplatin combinations, 11 patients in remission, and 35 healthy individuals. Intensities of the biomarker peaks were correlated with CT response of the patients and other clinical parameters.
We discovered 13 candidate biomarkers associated with different clinical parameters. Two biomarkers (2803 and 3953 Da) were significantly increased in patients compared with controls at all stages of disease. Analysis of pre- and post-CT paired serum samples revealed 7 biomarkers correlated with impact of CT. Of these 7 biomarkers, 2 (2509 and 2756 Da) were significantly increased and 5 (7588, 7659, 7765, 7843, and 8372 Da) were significantly decreased post-CT in either 1 or both CT cohorts. Four biomarkers from pre-CT sera were correlated with CT response, with 3 (2950, 13 510, and 14 855 Da) being significantly decreased and 1 (6701 Da) significantly increased in patients who did not respond to CT. Tandem mass spectrometric sequencing and/or immunoaffinity capture assay identified the 3953 Da biomarker as a fragment of interalpha-trypsin inhibitor precursor and 7765 Da biomarker as platelet factor-4.
Treatment-associated serum biomarkers found might serve to triage NPC patients for appropriate CT treatment.
Clinical Chemistry 03/2007; 53(2):241-50. · 7.91 Impact Factor
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[show abstract]
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ABSTRACT: A new strain of coronavirus has caused an outbreak of severe acute respiratory syndrome (SARS) from 2002 to 2003 resulting in 774 deaths worldwide. By protein chip array profiling technology, a number of serum biomarkers that might be useful in monitoring the clinical course of SARS patients were identified. This book chapter describes how the protein chip array profiling was carried out for this study. Briefly, SARS patients' serum samples were first fractionated in Q Ceramic HyperD ion exchange sorbent beads by buffers at different pH. Serum protein fractions thus obtained were then bound onto a copper (II) immobilized metal affinity capture (IMAC30 Cu [II]) ProteinChip Array or a weak cation-exchange (CM10) ProteinChip Array. After washing and addition of sinapinic acid, the chips were read in a Protein Biological System (PBS) IIc mass spectrometer. Ions were generated by laser shots and flied in a time of flight mode to the ion detector according to their mass over charge (m/z) ratio. The serum profiling spectra in SARS patients were acquired, baseline subtracted and analyzed in parallel with those from the control subjects by Ciphergen ProteinChip Software 3.0.2 with their peak intensities compared by a nonparametric two sample Mann-Whitney-U test. More than twelve peaks were differentially expressed in SARS patients with one at m/z of 11,695 (later identified to be serum amyloid A protein), which had increase in peak intensity correlating with the extent of SARS-coronavirus induced pneumonia as defined by a serial chest X-ray opacity score. The remaining biomarkers could also be useful in the study of other clinical parameters in SARS patients.
Methods in molecular biology (Clifton, N.J.) 02/2007; 382:313-31.
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Anne W M Lee,
W H Lau,
Stewart Y Tung,
Daniel T T Chua,
Rick Chappell,
L Xu,
Lillian Siu,
W M Sze,
T W Leung,
Jonathan S T Sham, Roger K C Ngan,
Stephen C K Law,
T K Yau,
Joseph S K Au,
Brian O'Sullivan,
Ellie S Y Pang,
S K O,
Gordon K H Au,
Joseph T Lau
[show abstract]
[hide abstract]
ABSTRACT: This randomized study compared the results achieved by concurrent chemoradiotherapy (CRT) versus radiotherapy (RT) alone for nasopharyngeal carcinoma (NPC) with advanced nodal disease.
Patients with nonkeratinizing/undifferentiated NPC staged T1-4N2-3M0 were randomized to CRT or RT. Both arms were treated with the same RT technique and dose fractionation. The CRT patients were given cisplatin 100 mg/m2 on days 1, 22, and 43, followed by cisplatin 80 mg/m2 and fluorouracil 1,000 mg/m2/d for 96 hours starting on days 71, 99, and 127.
From 1999 to January 2004, 348 eligible patients were randomly assigned; the median follow-up was 2.3 years. The two arms were well-balanced in all prognostic factors and RT parameters. The CRT arm achieved significantly higher failure-free survival (72% v 62% at 3-year, P = .027), mostly as a result of an improvement in locoregional control (92% v 82%, P = .005). However, distant control did not improve significantly (76% v 73%, P = .47), and the overall survival rates were almost identical (78% v 78%, P = .97). In addition, the CRT arm had significantly more acute toxicities (84% v 53%, P < .001) and late toxicities (28% v 13% at 3-year, P = .024).
Preliminary results confirmed that CRT could significantly improve tumor control, particularly at locoregional sites. However, there was significant increase in the risk of toxicities and no early gain in overall survival. Longer follow-up is needed to confirm the ultimate therapeutic ratio.
Journal of Clinical Oncology 10/2005; 23(28):6966-75. · 18.37 Impact Factor
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Kwok Hung Yu,
Sing Fai Leung,
Stewart Yuk Tung,
Benny Zee,
Daniel T T Chua,
Wai Man Sze,
Stephen C K Law,
Michael K M Kam,
To Wai Leung,
Jonathan S T Sham,
Anne W M Lee,
Joseph S K Au,
Edwin P Hui,
Wing Kin Sze,
Ashley C K Cheng,
T K Yau, Roger K C Ngan,
Frank C S Wong,
Gordon K H Au,
Anthony T C Chan
[show abstract]
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ABSTRACT: The purpose of this article is to report the overall survival (OS) outcome of patients with nasopharyngeal carcinoma (NPC) with local failure who received salvage treatment and to identify prognostic factors for OS.
Between January 1996 and December 2000, 2915 patients received primary radiotherapy (RT) with or without chemotherapy for nonmetastatic NPC. At a median follow-up of 3.1 years, 319 patients had developed local failure as the first failure, with or without synchronous regional/distant failure. OS was calculated from the start of primary RT. Univariate and multivariate analyses were performed to identify prognostic factors for OS in patients with isolated local failure.
The T classification distribution of the local failure (rT classification) was as follows: 68 (21%) rT1 to T2a, 92 (29%) rT2b, 82 (26%) rT3, and 77 (24%) rT4. The rT classification was the same as the initial T classification in 82% of patients. Two hundred seventy-five patients (86%) had isolated local failure, and 232 (84%) of them did not have any distant metastasis or regional failure develop during follow-up. Salvage treatment was given to 200 patients (73%) with isolated local failure. One hundred fifty-nine patients (80%) received reirradiation (108 external beam RT [EBRT], 44 brachytherapy, and seven EBRT plus brachytherapy), 22 patients (11%) underwent nasopharyngectomy with or without postoperative RT, and 19 patients (9%) were treated with chemotherapy alone. Four patients died of RT complications, and one died of chemotherapy toxicity in the absence of active NPC. The 3-year actuarial OS for patients with isolated local failure was 74%. On multivariate analysis, advanced initial T classification (hazard ratio [HR], 1.44; p = .0006) and the use of salvage treatment (HR, 0.54; p = .0038) were independent prognostic factors. For the subgroups of patients who had the same recurrent and initial T classification, salvage treatment was associated with improved OS only in the subgroup with T1 to T2 local failure (n = 127; p = 0.0446), but not in the subgroups with T3 (n = 48) or T4 (n = 54) disease.
Most patients with first local failure have localized disease. Salvage treatment is feasible in most of the patients with clinically isolated local failure. Patients who had early initial T classification have a more favorable prognosis. Subgroup analysis suggests that salvage treatment only prolongs survival in patients with T1 to T2 recurrent disease.
Head & Neck 06/2005; 27(5):397-405. · 2.40 Impact Factor
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Anthony T C Chan,
S F Leung, Roger K C Ngan,
Peter M L Teo,
W H Lau,
W H Kwan,
Edwin P Hui,
H Y Yiu,
Winnie Yeo,
F Y Cheung, [......],
Stephen Yau,
K T Yuen,
Frankie K F Mo,
Maria M P Lai,
Brigette B Y Ma,
Michael K M Kam,
Thomas W T Leung,
Philip J Johnson,
Peter H K Choi,
Benny C Y Zee
[show abstract]
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ABSTRACT: This phase III randomized study compared concurrent cisplatin-radiotherapy (CRT) versus radiotherapy (RT) alone in patients with locoregionally advanced nasopharyngeal carcinoma. A total of 350 patients were randomly assigned to receive external RT alone or concurrently with cisplatin at a dosage of 40 mg/m(2) weekly. The primary endpoint was overall survival, and the median follow-up was 5.5 years. The 5-year overall survival was 58.6% (95% confidence interval [CI] = 50.9% to 66.2%) for the RT arm and 70.3% (95% CI = 63.4% to 77.3%) for the CRT arm. In Cox regression analysis adjusted for T stage, age, and overall stage, the difference in overall survival was statistically significantly in favor of concurrent CRT (P = .049, hazard ratio [HR] = 0.71 [95% CI = 0.5 to 1.0]). Subgroup analysis demonstrated that there was no difference between overall survival in the arms for T1/T2 stage (P = .74, HR = 0.93 [95% CI = 0.59 to 1.4]), whereas there was a difference between the arms for T3/T4 stage (P = .013, HR = 0.51 [95% CI = 0.3 to 0.88]), favoring the CRT arm. The regimen of weekly concurrent CRT is a promising standard treatment strategy for locoregionally advanced nasopharyngeal carcinoma patients.
CancerSpectrum Knowledge Environment 05/2005; 97(7):536-9. · 14.07 Impact Factor
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Timothy T C Yip,
Johnny W M Chan,
William C S Cho,
Tai-Tung Yip,
Zheng Wang,
Ting-Lok Kwan,
Stephen C K Law,
Dominic N C Tsang,
John K C Chan,
King-Chung Lee,
Wai-Wai Cheng,
Victor W S Ma,
Christine Yip,
Cadmon K P Lim, Roger K C Ngan,
Joseph S K Au,
Angel Chan,
Wilina W L Lim
[show abstract]
[hide abstract]
ABSTRACT: A new strain of coronavirus (CoV) has caused an outbreak of severe acute respiratory syndrome (SARS), with 8098 individuals being infected and 774 deaths worldwide. We carried out protein chip array profiling analysis in an attempt to identify biomarkers that might be useful in monitoring the clinical course of SARS patients.
We performed surface-enhanced laser desorption ionization time-of-flight mass spectrometry on 89 sera collected from 28 SARS patients, 72 sera from 51 control patients with various viral or bacterial infections, and 10 sera from apparently healthy individuals.
Nine significantly increased and three significantly decreased serum biomarkers were discovered in the SARS patients compared with the controls. Among these biomarkers, one (11,695 Da) was identified to be serum amyloid A (SAA) protein by peptide mapping and tandem mass spectrometric analysis. When we monitored the SAA concentrations longitudinally in 45 sera from four SARS patients, we found a good correlation of SAA concentration with the extent of pneumonia as assessed by a serial chest x-ray opacity score. Increased SAA occurred in three of four patients at the time of extensive pneumonia as indicated by high x-ray scores. Over the course of gradual recovery in two patients, as assessed clinically and radiologically, SAA concentrations gradually decreased. In the third patient, the concentrations were initially increased, but were further increased with superimposed multiple bacterial infections. SAA was not markedly increased in the fourth patient, who had low x-ray scores and whose clinical course was relatively mild.
Protein chip array profiling analysis could be potentially useful in monitoring the severity of disease in SARS patients.
Clinical Chemistry 02/2005; 51(1):47-55. · 7.91 Impact Factor
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[show abstract]
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ABSTRACT: Nineteen Chinese patients with lymphoepithelioma-like carcinoma (LELC) of the lung were tested for Epstein-Barr virus (EBV) DNA in their serum samples by a quantitative polymerase chain reaction (PCR) technique. There was prospective serial monitoring of the serum in seven patients with advanced inoperable or relapsing disease. Five other patients at first diagnosis and two patients at relapse had only a single serum sample available. Serum samples were also taken from three other patients who had prior curative surgery and two patients with prolonged disease remission. Measurable levels of EBV DNA were detected in 11 of 12 patients with a pre-therapy serum sample and a clinically evident tumor. A low level of EBV DNA was also detectable in one of the two other patients whose first serum samples were obtained after some chemotherapy. There was no detectable EBV DNA in the five patients without evidence of tumor. The longitudinal serum EBV DNA profile of seven patients showed consistent correlation with response to therapy and clinical outcome. Patients with a pre-therapy serum EBV DNA >10,000 copies/mL had significantly inferior overall survival. This study suggests that circulating serum EBV DNA can be used as a tumor marker in the clinical management of patients with LELC of the lung.
Annals of the New York Academy of Sciences 06/2004; 1022:263-70. · 3.15 Impact Factor
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[show abstract]
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ABSTRACT: Nineteen Chinese patients with lymphoepithelioma-like carcinoma (LELC) of the lung were tested for Epstein-Barr virus (EBV) DNA in their serum samples by a quantitative polymerase chain reaction (PCR) technique. There was prospective serial monitoring of the serum in seven patients with advanced inoperable or relapsing disease. Five other patients at first diagnosis and two patients at relapse had only a single serum sample available. Serum samples were also taken from three other patients who had prior curative surgery and two patients with prolonged disease remission. Measurable levels of EBV DNA were detected in 11 of 12 patients with a pre-therapy serum sample and a clinically evident tumor. A low level of EBV DNA was also detectable in one of the two other patients whose first serum samples were obtained after some chemotherapy. There was no detectable EBV DNA in the five patients without evidence of tumor. The longitudinal serum EBV DNA profile of seven patients showed consistent correlation with response to therapy and clinical outcome. Patients with a pre-therapy serum EBV DNA >10,000 copies/mL had significantly inferior overall survival. This study suggests that circulating serum EBV DNA can be used as a tumor marker in the clinical management of patients with LELC of the lung.
Annals of the New York Academy of Sciences 05/2004; 1022(1):263 - 270. · 3.15 Impact Factor
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William C S Cho,
Timothy T C Yip,
Christine Yip,
Victor Yip,
Vanitha Thulasiraman, Roger K C Ngan,
Tai-Tung Yip,
Wai-Hon Lau,
Joseph S K Au,
Stephen C K Law,
Wai-Wai Cheng,
Victor W S Ma,
Cadmon K P Lim
[show abstract]
[hide abstract]
ABSTRACT: Nasopharyngeal cancer (NPC) is a common cancer in Hong Kong, and relapse can occur frequently. Using protein chip profiling analysis, we aimed to identify serum biomarkers that were useful in the diagnosis of relapse in NPC. Experimental Design: Profiling analysis was performed on 704 sera collected from 42 NPC patients, 39 lung cancer patients, 30 patients with the benign metabolic disorder thyrotoxicosis (TX), and 35 normal individuals (NM). Protein profile in each NPC patient during clinical follow up was correlated with the relapse status.
Profiling analysis identified two biomarkers with molecular masses of 11.6 and 11.8 kDa, which were significantly elevated in 22 of 31 (71%) and 21 of 31 (68%) NPC patients, respectively, at the time of relapse (RP) as compared with 11 patients in complete remission (CR; RP versus CR, P = 0.009), 30 TX (RP versus TX, P < 0.001), or 35 NM (RP versus NM, P < 0.001). The markers were also elevated in 16 of 39 (41%) lung cancer patients at initial diagnosis. By tryptic digestion, followed by tandem mass spectrometry fragmentation, the markers were identified as two isoforms of serum amyloid A (SAA) protein. Monitoring the patients longitudinally for SAA level both by protein chip and immunoassay showed a dramatic SAA increase, which correlated with relapse and a drastic fall correlated with response to salvage chemotherapy. Serum SAA findings were compared with those of serum Epstein-Barr virus DNA in three relapsed patients showing a similar correlation with relapse and chemo-response.
SAA could be a useful biomarker to monitor relapse of NPC.
Clinical Cancer Research 01/2004; 10(1 Pt 1):43-52. · 7.74 Impact Factor
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[show abstract]
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ABSTRACT: To determine the clinical outcome, prognostic factors, and effect of adding combination chemotherapy to radiation therapy on disease control and survival in early stage nasal natural killer (NK)/T-cell lymphoma.
A retrospective "intent to treat" analysis was carried out on 79 patients treated consecutively with curative intent between 1977 and June 2001. They all had early stage (Ann Arbor Stage I(E): 63, II(E):16) nasal NK/T-cell lymphoma. Sixty-one were planned for combined modality treatment (CMT); radiotherapy alone (RT) was intended for 18. Three to 6 cycles of anthracycline-containing regimens were aimed at for patients intended for CMT. Patients selected for RT were generally older or treated during the earlier part of the study period.
The overall complete response (CR) rate was 68.4% (54/79), of whom 44.4% (24/54) relapsed after 54.9 months median follow-up of the survivors. The 5-year disease-free survival (DFS) and overall survival (OS) rates were 35.5% and 37.9%, respectively. On multivariate analysis, good performance status (Eastern Cooperative Oncology Group [ECOG] <2) was shown to be a significant favorable factor for DFS (p = 0.011), whereas good performance status (ECOG <2) and Ann Arbor Stage I(E) disease were shown to be significant favorable factors for OS (p = 0.001 and p = 0.013, respectively). The type of intended treatment was not a significant factor for DFS (5-year DFS CMT vs. RT = 35.8% vs. 30.5%, p = 0.795) or OS (5-year OS CMT vs. RT = 40.3% vs. 29.8%, p = 0.693) though only 2 of the 16 Stage II(E) patients were intended for RT alone. Resistance to treatment, especially to chemotherapy, was common. Of 61 patients intended to be given CMT, 31 showed disease progression while receiving chemotherapy, of whom 17 progressed locoregionally. Nine of the latter group were rendered CR by salvage radiotherapy.
The overall outcome in early stage nasal NK/T-cell lymphoma is poor. Performance status and Ann Arbor stage are significant factors influencing DFS and OS. The addition of anthracycline-containing chemotherapy to radiotherapy does not appear to confer any survival benefit in Stage I(E) patients. Therefore, radiation therapy remains the mainstay of treatment for this lymphoma type.
International Journal of Radiation OncologyBiologyPhysics 09/2002; 54(1):182-90. · 4.11 Impact Factor
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ABSTRACT: The purpose of this work was to study the sera of patients with lymphoepithelioma-like carcinoma (LELC) of the lung for circulating EBV DNA.
Prospectively collected serum samples from five female patients with advanced, inoperable LELC of the lung were measured for free circulating EBV DNA using a quantitative PCR technique. EBV-encoded small RNA (EBER)-1 was assayed in serial serum samples of three of the five patients, either from the start or during the initial phase of chemotherapy/radiotherapy until their terminal event or last follow-up. There was only a single-point sample for analysis in the fourth and fifth patients. Six other patients with LELC of the lung were also retrospectively identified, and their sera were tested for EBER-1 at either the first visit plus the last follow-up visit (n = 2), the first visit only (n = 2), or the last follow-up visit only (n = 2).
Prospectively collected serum samples from five patients and retrospectively collected serum samples from two patients who had clinical disease at initial serum measurement showed detectable levels of EBER-1. Retrospectively collected serum samples from four patients with no clinical disease had negative sera. There is consistent correlation between the clinical response to treatment and subsequent clinical course of LELC and serum EBER-1 levels in the three prospective patients with longitudinal serum monitoring.
This study shows for the first time that free EBV DNA can be detected in the serum of patients with LELC of the lung and further suggests the feasibility of its use for monitoring response to therapy in advanced cases.
Clinical Cancer Research 05/2002; 8(4):986-94. · 7.74 Impact Factor
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ABSTRACT: Central nervous system (CNS) metastasis from nasopharyngeal carcinoma (NPC) is an extremely rare occurrence, although direct intracranial invasion is not infrequent in patients with NPC at a locally advanced stage. Only five other patients have been reported in detail in the English literature.
The clinical records of two such patients with NPC who were diagnosed with metastasis to the spinal cord (intradural) and to the occipital lobe, respectively, were reviewed. The literature was searched for a review of similar incidents.
Both patients had locally advanced disease at the time of presentation and were treated with neoadjuvant chemotherapy and radical radiotherapy. The CNS metastases in both patients were accompanied by disease recurrences in multiple sites after a prolonged period of clinical remission. Spread through cerebral spinal fluid was postulated for the patient with spinal cord metastasis, and hematogenous spread was postulated for the patient with brain metastasis. Aggressive surgical resection with or without postoperative radiotherapy conferred reasonable survival and symptom control. The patient with brain metastasis died 6 months later of lung metastasis, whereas the other patient is still alive 40 months from the diagnosis of spinal metastasis.
Good symptom control and disease control can be achieved for patients with CNS metastasis after surgery with or without radiotherapy. After aggressive therapy, the ultimate survival depends on control of extracranial disease.
Cancer 02/2002; 94(2):398-405. · 4.77 Impact Factor
