W.T. Leung

Quantitative evaluation of thallium-201 uptake in predicting chemotherapeutic response of osteosarcoma.

Thallium-201 has been shown to be useful in predicting tumour viability in patients undergoing neoadjuvant chemotherapy for osteogenic sarcoma. Early studies relied upon qualitative assessment of analog images to obtain predictive results. Recently, the lesion to normal tissue uptake ratio of201Tl has been used in evaluating bone and soft tissue sarcomas. This study attempts to quantitate changes in tumour to normal tissue ratio following chemotherapy. Eight consecutive patients with classical osteosarcoma received standard preoperative chemotherapy with a combination of cisplatin, adriamycin and high-dose methotrexate.201Tl gamma scintigraphic images were obtained both before and after chemotherapy. The average counts taken over the tumour divided by that from the contralateral normal tissue area yielded a tumour-to-normal tissue (T/N) ratio. The percentage change in the T/N ratio before and after preoperative chemotherapy was correlated with the percentage of tumour necrosis from pathological section. The median post-chemotherapy T/N ratio was 1.85 (range 0.5–7.7). The median percentage change in T/N ratio after chemotherapy was -58% (range +26% to -83%). The median percentage of necrosis from pathological section was 80% (range 0%–95%). There was a good correlation between the percentage of tumour necrosis and the percentage change in TIN ratio (rank correlation coefficientr=0.84,P=0.0085). Quantitative assessment of changes in 201+1 uptake by osteosarcoma correlates well with tumour necrosis after preoperative chemotherapy. This method may be used to predict response to chemotherapy at an earlier stage, enabling the clinician to consider alternative chemotherapeutic regimens or salvage surgery.

Early tumour response and treatment toxicity after hyperfractionated radiotherapy in nasopharyngeal carcinoma

The aim of the present study was to undertake a planned interim analysis of a prospective randomized trial comparing the tumour response and the acute and subacute complications of hyperfractionated radiotherapy and conventional radiotherapy in non-metastatic nasopharyngeal carcinoma (NPC). 100 patients with newly diagnosed non-metastatic NPC were randomized to receive either conventional radiotherapy (Arm I) or hyperfractionated radiotherapy (Arm II). Stratification was done according to the T-Stage (modified Hos T-Stage classification). The biological effective dose (10 Gy) to the primary and the upper cervical lymphatics were 75.0 and 73.1 for Arm I and 84.4 and 77.2 for Arm II, respectively. Hyperfractionated radiotherapy was associated with significant mucositis which is of higher grade than conventional radiotherapy (p = 0.0001), but the duration of mucositis was similar between the two Arms and all study patients completed radiotherapy on schedule without interruption of radiotherapy. Early survival and tumour recurrence rates were comparable between the Arms. The preliminary results indicate that the hyperfractionated radiotherapy has excellent patient compliance in Chinese patients, with acceptable acute and subacute toxicities and the local and regional complete tumour response rates being comparable with conventional radiotherapy. The significance of the time required after start of radiotherapy to achieve a complete tumour response is discussed.

Phase II studies with DaunoXome in patients with nonresectable hepatocellular carcinoma: clinical and pharmacokinetic outcomes.

Abstract A total of 14 Chinese patients with inoperable hepatocellular carcinoma received a liposomal formulation of daunorubicin (DaunoXome) at a dose equivalent to 100 mg/m2 of the free drug every 3 weeks. Altogether, 12 patients were assessable for response; 2 patients had stable disease for 8 weeks, but all eventually developed progressive disease and there was no responder. The drug was well tolerated, with no evidence of cardiac toxicity being observed. Deterioration of liver-function tests was attributed to progressive tumors in the terminal stage of the disease. Pharmacokinetics studies revealed a biexponential decay for daunorubicin in association with mean initial and terminal half-lives of 1.8 and 7.4 h, respectively, and a mean total clearance of 15.0 ± 5.5 ml/min. The AUC ratio between the metabolite daunorubicinol and daunorubicin was 0.07. These data differ markedly from the pharmacokinetics of the free drug.

Serum levels of CYFRA 21-1 in nasopharyngeal carcinoma and its possible role in monitoring of therapy

CYFRA 21-1 is a fragment of cytokeratin expressed by simple epithelia and their malignant counter-parts. Serum CYFRA 21-1 levels were studied in 240 new cases of nasopharyngeal carcinoma and 19 patients who developed distant metastases. A reference range of < 2 U/ml for our local Chinese population was established in 55 sex- and age-matched healthy volunteers. The nasopharyngeal carcinoma patients had significantly higher marker levels than the healthy controls and the mean level increased with advancing stage. However, the low percentage of elevation in early stages means that the marker is not useful for screening. The overall percentage (52.5) of elevation in 240 newly diagnosed squamous cell carcinoma of the nasopharynx is comparable to that of squamous cell carcinoma of the lungs, suggesting that the expression of CYFRA 21-1 is related to the cell type rather than the tissue type of the carcinoma, 46 (95.8%) of 48 patients with metastatic nasopharyngeal carcinoma showed an elevated value of CYFRA 21-1. This extremely high percentage implies that it is very unlikely for a patient with a normal value to have distant metastasis. This may permit major economies in radiological screening for distant metastasis. Preliminary results from serial measurement of the marker indicated its potential for monitoring response to treatment and for early detection of distant metastasis.

Treatment of inoperable hepatocellular carcinoma by intra-arterial Lipiodol and 4'-epidoxorubicin

SummaryA total of 30 patients presenting with inoperable hepatocellular carcinoma (HCC) were treated with intrahepatic arterial Lipiodol (5 ml) and 4′-epidoxorubicin (90 mg/m2) once every 4 weeks. The treatment results included no complete response, 2 partial responses, 6 cases of static disease and 19 cases of progressive disease. The median survival was 18.9 weeks. All patients had died by the time of this writing, with survival duration ranging from 4.1 to 87.3 weeks. Toxicities were minimal and included anaemia and alopecia. As compared with a historic control group that had received the same dose of intravenous 4′-epidoxorubicin, the treatment group showed similar response rates but developed fewer toxicities. There was no significant survival benefit over the control group. We concluded that although this form of treatment had comparable activity and produced fewer side effects, it provided no survival benefit over intravenous treatment. The slight prolongation of survival achieved in the treatment group as compared with the control arm might have been due to case selection.

Phase II study of high-dose ifosfamide in hepatocellular carcinoma

SummaryA phase II study of high-dose ifosfamide in hepatocellular carcinoma was conducted among 17 Chinese patients. The dose of ifosfamide used was 2.5 g/m2 daily given as a continuous infusion for 5 days. In all, 15 patients were evaluable for tumour response. There was no complete or partial responder. The treatment was well tolerated. The most frequent toxicity was alopecia, which occurred in 11 patients, and 5 patients developed mild haematological toxicity. There was no evidence of liver or bladder toxicity. Overall, 14 patients were evaluable for survival. The median survival was 92 days (range, 30–568 days). We conclude that high-dose ifosfamide is well tolerated but ineffective in hepatocellular carcinoma in Chinese patients.

Strong association between hyperferritinaemia and metastatic disease in nasopharyngeal carcinoma.

We have investigated the role of serum ferritin, in relation to disease stages, in patients with nasopharyngeal carcinoma. Patients with localised disease (Hos stage I-IV) had levels which were not significantly different from age, sex matched normal subjects and there was no relationship between mean serum ferritin levels and stage. However, in patients with metastatic disease levels were grossly elevated with mean levels increased more than 6-fold compared to normal subjects and patients with localised disease. Furthermore, among the small group of patients with localised disease but hyperferritinaemia, the subsequent development of metastatic disease within 1 year was significantly much higher (32.4%) than in those with levels falling within the reference range (10.3%). Hyperferritinaemia is strongly associated with, and may predict, metastatic disease in patients with nasopharyngeal carcinoma.

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 Hos 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.

A rare site and appearance for lymphomatous recurrence

A patient with a recurrence of large cell lymphoma is reported. There was psoas muscle involvement, which showed ring enhancement post-intravenous contrast on CT scan. Ring enhancement in skeletal muscle infiltration by lymphoma has not been described previously.