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Biomedical subjects

A T Chan

Publications and source records attributed to A T Chan.

At least 55 records · Page 3Linked to original sources

Application of the international prognostic index in a study of Chinese patients with non-Hodgkin's lymphoma and a high incidence of primary extranodal lymphoma.

BACKGROUND: Chemotherapy containing anthracycline is the standard initial treatment for aggressive non-Hodgkin's lymphoma (NHL), and the International Prognostic Index (IPI) is widely accepted as the standard tool for determining the prognosis of patients with this disease. However, the data on which the IPI was based primarily came from studies conducted in Western countries. It may not be directly applicable to Asian populations, in which the incidence of primary extranodal lymphoma (PENL) is known to be high. METHODS: The authors conducted a retrospective study of 218 patients with aggressive NHL who were treated with chemotherapy. They analyzed the distribution of stage and pathology, prognostic factors, toxicity, and treatment outcome. The IPI was then applied and its ability to identify distinct prognostic groups tested. RESULTS: Eighty-six patients (39.4%) had lymph node lymphoma (LNL) and 132 (60.6%) had primary extranodal lymphoma (defined as non-Hodgkin's lymphoma with primary presentation, bulk of disease, and histologic confirmation at an extranodal site). The most common primary extranodal sites were the stomach (22%) and Waldeyer's tonsillar ring (18.9%). The complete response rate of PENL patients to chemotherapy containing anthracycline was 52%, as compared with 64% of the LNL group. The 5-year survival rates for patients with LNL and PENL were 57.4% and 52.1%, respectively. The toxicity in the two patient groups was similar. Four of the prognostic factors in the IPI-age, serum LDH, performance status, and disease stage-predicted significantly different survival for PENL and LNL patients. However, the number of extranodal sites involved was not a significant predictive variable in PENL. CONCLUSIONS: The IPI was applicable to this Chinese population in which the incidence of PENL was high, although the number of extranodal sites did not achieve statistical significance as a risk factor. A proposal for modification was made. Chemotherapy containing anthracycline was an effective treatment for both PENL and LNL patients.

Adolescent↗

The role of chemotherapy in the management of nasopharyngeal carcinoma.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a radiosensitive tumor for which there is a high local control rate after radical radiotherapy (RT). However, for patients with locoregionally advanced disease, the rate of distant metastasis is high and the 5-year overall survival rate is poor. METHODS: A review of retrospective and prospective clinical studies was performed to assess the role of chemotherapy in three settings: metastatic disease; neoadjuvant and/or adjuvant; and concurrent chemotherapy with radiotherapy. RESULTS: Cisplatin-based combination chemotherapy results in a high response rate in patients with metastatic NPC, and a subgroup may achieve long term disease free survival. The use of neoadjuvant and adjuvant chemotherapy to treat locoregionally advanced disease has resulted in consistently high response rates, but no randomized trial to date has demonstrated an improvement in overall survival. A recent Head and Neck Intergroup study randomized patients in the United States to receive concurrent chemotherapy (cisplatin) and radiotherapy or radiotherapy only. Although this approach demonstrated significant benefit in overall survival favoring the use of concurrent chemotherapy and radiotherapy, its applicability in geographic areas of high NPC incidence remains to be proven. CONCLUSIONS: NPC is a chemosensitive tumor, and patients with metastatic disease have a high response rate. Further prospective studies will define the standard approach to treating locoregionally advanced NPC, which is likely to incorporate into the primary treatment some form of systemic chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗

How successful is high-dose (> or = 60 Gy) reirradiation using mainly external beams in salvaging local failures of nasopharyngeal carcinoma?

PURPOSE: To evaluate the efficacy of high-dose (> or = 60 Gy) reirradiation using mainly external beams in salvaging local failures of nasopharyngeal carcinoma (NPC) after modern primary radical radiotherapy that delivered radical dose-to-target volumes defined by CT scan. METHODS AND MATERIALS: Nine hundred and three patients with nondisseminated NPC whose primary radical radiotherapy was administered between 1984 and 1989 inclusive were studied. One hundred and seventy-six had local failures comprising 9 persistences and 167 recurrences. In 10 patients the local failures were preceded or accompanied by (within 2 months) distant metastases, and these were given supportive treatment or palliative radiotherapy in low dose (< 60 Gy) if symptomatic. Most of the rest (123 of 166) were treated with either reirradiation to high dose (> or = 60 Gy) using mainly external photon beams (n = 103) or nasopharyngectomy with/without radical neck dissection with/without postoperative radiotherapy (n = 20). The remainder (n = 43) received only palliative treatments because of poor general condition and/or patients' refusal of radical treatments. The primary radiotherapy was planned on the basis of target volumes defined by CT scan and given to a standard nasopharyngeal dose of 62.5 Gy/29 fractions/6 weeks. In the presence of parapharyngeal involvement, an additional boost of 20 Gy/10 fractions/2 weeks was given via a posterior oblique photon beam. If local residual tumors were diagnosed at 4-6 weeks after the completion of external radiotherapy, an additional boost of 24 Gy/3 fractions/15 days was given by intracavitary intubation. For the local failures given high-dose reirradiation, the target volume was defined by CT scan and treated by a two-field or a three-field photon arrangement with or without additional dose supplement by intracavitary intubation. Nasopharyngectomy was performed via the transcervico-mandibulo-palatal approach or the maxillary swing approach. Radical neck dissection was only performed for the clinically evident nodal failures. RESULTS: With a median follow-up of 20 months (range 2.5-81 months) since the diagnosis of local failure, the actuarial 5-year overall survival, further relapse-free survival and free-from-local-tumor rates were 9.4, 11.5, and 18.7%, respectively, for the 123 patients treated by either high-dose reirradiation (n = 103) or nasopharyngectomy (n = 20). Palliatively treated patients (n = 43) had a survival comparable to patients whose local failures were preceded or accompanied by distant metastasis (n = 10). Reirradiation to high dose (> or = 60 Gy) mainly by external photon beams achieved a 5-year overall survival of 7.6% and 5-year local control of 15.2% with significant complications. Radiation-induced temporal lobe encephalopathy was radiologically evident in 21 patients (20.4%), and 13 of these 21 patients were symptomatic. It could have been the cause of death in three patients who also suffered from uncontrolled local tumor. Significant morbidity was also associated with the other frequent radiation complications, including xerostomia, trismus, and deafness. Uni- and multivariate analyses indicated that brief initial disease-free interval between completion of primary radiotherapy and diagnosis of local failures and advanced recurrent T-stage and recurrent N-stage were significant prognosticators predicting poor survival and/or further local failure after reirradiation. These patients were unlikely to benefit from the treatment. Nasopharyngectomy (+/- neck dissection +/- postoperative radiotherapy) was associated with earlier recurrent T-stages (mostly rT1 and rT2) and better survival and local control than reirradiation. However, restricting the comparison to rT1 and rT2 still demonstrated the superior results in favor of nasopharyngectomy, which could not be explained by the selection of less advanced lesions or patients with better performance status for surgery. (ABSTRACT TRUNCATED)

Adult↗

Phase II study of Temodal in the treatment of patients with advanced nasopharyngeal carcinoma.

PURPOSE: A single-institution phase II trial of Temodal (temozolomide, SCH52365) in Chinese patients with advance nasopharyngeal carcinoma was undertaken to determine the efficacy and safety of the drug in this population. METHODS: A total of 14 patients with metastatic or locoregionally recurrent nasopharyngeal carcinoma were entered into the study. One patient was unevaluable. Temodal was given at doses of 150 or 200 mg/m2 daily on days 1-5 every 28 days. RESULTS: In all, 30 cycles of Temodal were given with no significant toxicity. All 13 (100%) evaluable patients had progressive disease after 2 (84.6%) or 4 (15.4%) courses. CONCLUSION: Temodal given on this schedule has no activity in advanced nasopharyngeal carcinoma.

Adult↗

Ulnar artery as a coronary bypass graft.

BACKGROUND: The ulnar artery has been used as a coronary bypass graft in 8 patients when it was deemed unsafe to harvest the radial artery after evaluation of the arterial circulation in the forearm and hand. METHODS: The ulnar artery was removed from the lower three quarters of the forearm, along with its satellite veins. Dissection was commenced distally near the wrist and extended proximally to where the ulnar artery passed between the two heads of origin of the flexor digitorum superficialis. The artery was divided distally above the wrist joint and proximally at a point immediately below the origin of the common interosseus artery. RESULTS: Ten ulnar arteries were removed for use as coronary artery bypass grafts; two were rejected, one because of severe calcification and the other because of atherosclerotic occlusion. The remaining eight ulnar arteries were grafted successfully to coronary arteries other than the left anterior descending. No early hand or cardiac complications were observed. CONCLUSIONS: The ulnar artery is an alternative coronary artery bypass graft that may be used when the radial artery is dominant and cannot be removed without risk. The ulnar artery is in close proximity to the ulnar nerve and harvesting has the potential to injure the nerve. Therefore, until the use of the ulnar artery has been more fully evaluated it should be used only when other options have been exhausted.

Aged↗

The significance of keratinizing squamous cell histology in Chinese patients with nasopharyngeal carcinoma.

Six hundred and ninety-three Chinese patients with non-metastatic nasopharyngeal carcinoma (NPC) were treated at one institution under a uniform protocol between 1984 and 1989. The tumour histology of these patients was subjected to a standardized review and classified into two distinct groups of World Health Organization (WHO) type I (keratinizing squamous cell carcinoma) (n = 13) or WHO types II and III (non-keratinizing carcinoma and undifferentiated carcinoma) (n = 662). The differentiation between the two groups was uncertain in 18 patients. The patient characteristics and clinical outcome after a uniform treatment policy of the two groups were not statistically significantly different. The low incidence of WHO type I NPC may account for the lack of prognostic significance of this histological subtype in Chinese populations.

Actuarial Analysis↗

A phase II study of combination paclitaxel and carboplatin in advanced nasopharyngeal carcinoma.

The aim of this study was to determine the efficacy and toxicity of combination paclitaxel and carboplatin chemotherapy in patients with metastatic and/or locoregionally advanced nasopharyngeal carcinoma (NPC). Patients with metastatic and/or locoregionally advanced NPC were treated with carboplatin calculated according to an AUC of 6 mg ml/min (based on Calvert formula) given as an intravenous (i.v.) bolus, followed by paclitaxel 135 mg/ml2 given as an i.v. infusion over 3 h with standard premedication. Cycles were given 3 weekly to a maximum of six. From January 1996 to November 1997, 27 patients were entered and assessable for response and toxicity. A total of 122 cycles were given and the median number of cycles given was five. The overall response rate was 59% (16/27). There were 3 (11%) complete responses, 13 (48%) partial responses, 5 (19%) static disease and 6 (22%) progressive disease. Toxicity was mainly haematological including: grade 3/4 neutropenia (39 cycles, 32%), grade 3/4 anaemia (nine cycles, 7%), grade 3/4 thrombocytopenia (eight cycles, 7%). There were three episodes of neutropenic fever (3%). Non-haematological toxicities were mild and infrequent. Paclitaxel and carboplatin combination chemotherapy is active in NPC and has tolerable toxicity. Further study with dose escalation is required to assess its optimal efficacy.

Adult↗

Controversies in the management of locoregionally advanced nasopharyngeal carcinoma.

In patients with locoregionally advanced nasopharyngeal carcinoma the results of treatment with conventional radiotherapy are unsatisfactory, with significant rates of both distant metastases and local recurrences. The use of neoadjuvant and adjuvant chemotherapy has resulted in consistently high response rates, but no randomized trial has yet demonstrated an improvement in overall survival. Altered-fractionation radiation techniques have not been proven to improve survival in locoregionally advanced nasopharyngeal carcinoma, and extreme caution is required to minimize unpredicted neurological toxicities. An interim analysis of a Head and Neck Intergroup study randomly assigning patients to receive concurrent chemotherapy and radiotherapy and adjuvant chemotherapy or radiotherapy alone has demonstrated significant benefit in overall survival favoring the use of concurrent chemotherapy and radiotherapy. Whether this regimen is applicable to all ethnic and histological groups, however, remains to be proven.

Antineoplastic Combined Chemotherapy Protocols↗

Nasal lymphoma: results of local radiotherapy with or without chemotherapy.

BACKGROUND: Primary nasal lymphoma is a rare disease. Although most patients are initially seen in early Ann Arbor stages, their prognosis is poor. The prognostic significance of local tumor bulk has not been well studied. METHODS: Twenty-one patients with nasal lymphoma treated between 1985 and 1992 were retrospectively studied. Sixteen patients (76%) below the age of 75 years received combined radiotherapy and chemotherapy. One young patient with early disease and 4 elderly patients had radiotherapy alone. Twelve cases (57%) were diagnosed as pleomorphic T-cell lymphoma based on typical histologic features alone. Immunophenotyping was performed in 10 cases; 8 were T cell and 2 were B cell. Seventeen patients (81%) had Ann Arbor clinical stage IE disease, and 4 had stage IIE disease. The local tumor extent was assessed by endoscopy in all patients and by computerized tomography (CT) in 14 patients. Eleven local tumors (52%) extended to the posterior ethmoids, sphenoid sinus, orbit, or beyond. Using a T-stage system, the prognostic significance of local tumor bulk was evaluated for stage IE patients. RESULTS: At a median follow-up time of 16.8 months, the lymphoma recurred in 13 patients; 10 patients had systemic relapse and 10 patients, local relapse. The 5-year actuarial overall survival rate was 24%. Complete response to chemotherapy was achieved in 5 of 16 patients (31%). Four of the 6 patients who remained alive and disease-free were chemotherapy complete responders. Among stage IE patients, those with early and those with advanced local disease did not have significantly different survival. CONCLUSIONS: In view of the high systemic and local relapse rates, more-effective chemotherapy is needed to improve the survival rates, and the role of combined chemotherapy and radiotherapy should be evaluated. Further studies are required to identify patients at high risk of relapse for clinical trials with investigational treatment.

Adult↗

Assessment of proliferating cell nuclear antigen in nasopharyngeal carcinoma tissue and its relation to clinical findings.

47 newly diagnosed patients with nasopharyngeal carcinoma (NPC) were studied using the proliferating cell nuclear antigen (PCNA) immunostaining technique. The results were reproducible as shown by assessment of three separate sections performed for each patient. No statistical correlation was found between PCNA labelling index (LI) and Ho's clinical staging or time required to achieve complete remission of the local disease. A higher PCNA LI was associated with a poorer disease-free survival. The literature on the use of PCNA in human tumours is reviewed.

Adolescent↗

Carbamazepine-induced lymphadenopathy mimicking Ki-1 (CD30+) T-cell lymphoma.

A 22 year old male receiving carbamazepine for a bipolar affective disorder presented with pyrexia, generalized rash, lymphadenopathy and hepatosplenomegaly. He was thrombocytopenic and liver function tests revealed a hepatitic picture. Lymph node histology suggested a T-cell lymphoma with many large cells possessing blastic features, and expressing CD3 and CD30 antigens. The abnormalities resolved completely within nine weeks of discontinuing carbamazepine, indicating that the presenting lymphadenopathy was secondary to lymphoid activation, ie; a pseudolymphoma rather than a malignant lymphoma. This is the first reported case of carbamazepine-induced lymphadenopathy with CD30+ cells. It illustrates the potential danger of relying too heavily on CD30 positivity as an indicator of malignancy.

Adult↗

Transdermal fentanyl for severe cancer-related pain.

A prospective phase II study was conducted to define the analgesic efficacy, acceptability and toxicity of the transdermal therapeutic system (TTS) of fentanyl in Chinese patients with severe cancer-related pain. A total of 14 patients was treated with TTS fentanyl at doses ranging from 25 to 100 micrograms h-1; initial doses were chosen according to their previous opioid requirement. Standard supportive therapy was given as required. A brief pain inventory (using a 10-point scale) was used to assess patients at days 0, 7 and 14. Pain control on day 14 with TTS fentanyl was successful in six patients, with a reduction in the common side-effects of other opioids and improvement in general well-being. Seven patients did not complete the 14-day trial: two developed dizziness and nausea within 3 h of application; and in five, TTS fentanyl was insufficiently flexible to control increasing pain during the first week. TTS fentanyl was effective and well tolerated in 43% of patients. Acute dizziness and nausea within the first few hours after application and the relative inflexibility of dose-adjustment both limited the use of TTS fentanyl.

Administration, Cutaneous↗

Phase II study of the combination of carboplatin and 5-fluorouracil in metastatic nasopharyngeal carcinoma.

A carboplatin and 5-fluorouracil (CF) chemotherapy protocol was designed to evaluate tumor response and toxicity in patients with metastatic nasopharyngeal carcinoma (NPC). Patients with metastatic NPC were treated with a maximum of eight courses of CF. Carboplatin was given at 300 mg/m2 by intravenous bolus on day 1 and 5-fluorouracil at 1 g/m2 per day by continuous infusion on days 1-3; cycles were repeated once every 3 weeks. A total of 42 patients were evaluable for response and toxicity. They received a median of 6 courses (range 2-8) of chemotherapy. The overall response rate was 38% (16/42), comprising 7 complete responses (CR, 17%) and 9 partial responses (PR, 21%). The median survival was 12.1 months (range 6-54.2 months). The treatment was well tolerated. Toxicity was mainly bone marrow suppression. There were four episodes of neutropenic fever, but no renal toxicity or treatment-related death was documented. The combination of carboplatin given at a fixed dose of 300 mg/m2 for 1 day and 5-fluorouracil given at 1 g/m2 per day for 3 days produced an objective response rate of 38% and tolerable side effects.

Adult↗

In vitro uptake of bromodeoxyuridine by human nasopharyngeal carcinoma (NPC) and its relation to clinical findings.

A cell kinetic study of 27 newly diagnosed patients with nasopharyngeal carcinoma (NPC) using the in vitro bromodeoxyuridine (BrdU) technique was performed. The results were reproducible as demonstrated by three independent sections performed on each patient. No correlation between BrdU labelling index (LI) and Ho's clinical staging was found. A higher LI was associated with the development of distant metastases (P = 0.057). Statistically significant correlation was found between low LI and longer duration required to achieve complete remission in the primary site of disease (P = 0.026). This study suggests a potential role for in vitro BrdU labelling index as a prognosticator for NPC prior to treatment.

Adult↗

Radiotherapy for extreme hypertrophic pulmonary osteoarthropathy associated with malignancy.

A patient with florid hypertrophic pulmonary osteoarthropathy (HPOA) associated with metastatic nasopharyngeal carcinoma is presented. Despite the presence of metastatic disease in the thorax and in bone, the patient's main symptom was severe pain from the HPOA, which was temporarily relieved by chemotherapy. Her disease subsequently progressed during chemotherapy and the pain became resistant to conventional treatment, including high dose morphine, non-steriodal anti-inflammatory agents and steriods. It was only with local radiation to the involved joints that the pain could be controlled. Our patient demonstrates that local radiotherapy is an option for the palliation of extreme HPOA.

Adult↗

Primary mediastinal malignant germ cell tumour. Single institution experience in Chinese patients and correlation with specific alpha-fetoprotein bends.

Ten Chinese patients were reviewed, all with mediastinal germ cell tumours and treated in our centre during the past 8 years. Three patients with pure seminomas were given chemotherapy with or without radiotherapy. AB achieved complete remission with no relapse. Seven patients with non-seminomatous germ cell tumours (NSGCT) were given chemotherapy, with or without surgery. Two patients with rapid decay of alpha-fetoprotein (AFP) levels (half-life less than or equal to 7.2 days) during chemotherapy achieved complete remission with no relapse. Five patients with prolonged decay of AFP levels (half-life > 7.2 days) failed to achieve complete remission with initial chemotherapy and all but one patient died between 5 and 9 months later. One patient developed acute megakaryocytic leukaemia. Using isoelectric focusing, AFP bands specific to NSGCT were quantified, and comparison was made with the total AFP in five cases. In each case the change in NSGCT-specific AFP concentration in response to therapy closely paralleled that of total AFP. Estimation of NSGCT-specific AFP offers no apparent advantage in monitoring disease response or progression.

Adult↗