Radiation dose measurements for personnel performing 90Y-ibritumomab tiuxetan administration: a comparison between two injection methods for dose reduction.

The purpose of this study was to directly measure, using thermoluminescent dosimeters, the radiation doses received by radiation team members performing (90)Y-ibritumomab tiuxetan administration. The occupational doses associated with two injection methods for patient administration - an automatic syringe driver and an injection box - were compared. The associated risks, namely cancer induction and hereditary effect, were also estimated from the results and compared with risk factors recommended by the International Commission on Radiological Protection publication 103. The results showed that the doses received by the index and thumb of the right hand and the index finger of the left hand of the radiation oncologist were significantly reduced by using the injection box method. The difference in the dose received by the medical physicist using the two methods was not statistically significant. It was observed that three pairs of latex gloves could further reduce the dose to the hands. The radiological risks of cancer induction and hereditary effect were negligible: of the order of 10(-6) and 10(-7) per (90)Y-ibritumomab tiuxetan administration, respectively, for both methods. However, the results of our study also showed that it would be possible in a busy centre for pregnant women to receive a dose of (90)Y-ibritumomab tiuxetan that exceeds the recommended annual dose limit for the surface of the abdomen.

Functional polymorphisms in the BRCA1 promoter influence transcription and are associated with decreased risk for breast cancer in Chinese women.

BACKGROUND: The BRCA1 gene is an important breast-cancer susceptibility gene. Promoter polymorphisms can alter the binding affinity of transcription factors, changing transcriptional activity and may affect susceptibility to disease. METHODS AND RESULTS: Using direct sequencing of the BRCA1 promoter region, we identified four polymorphisms c.-2804T-->C (rs799908:T-->C), c.-2265C-->T (rs11655505:C-->T), c.-2004A-->G (rs799906:A-->G) and c.-1896(ACA)(1)-->(ACA)(2) (rs8176071:(ACA)(1)-->(ACA)(2)) present in Hong Kong Chinese. Each polymorphism was studied independently and in combination by functional assays. Although all four variants significantly altered promoter activity, the c.-2265T allele had stronger binding than the C allele, and the most common mutant haplotype, which contains the c.-2265T allele, increased promoter activity by 70%. Risk association first tested in Hong Kong Chinese women with breast cancer and age-matched controls and replicated in a large population-based study of Shanghai Chinese, together totalling >3000 participants, showed that carriers of the c.-2265T allele had a reduced risk for breast cancer (combined odd ratio (OR) = 0.80, 95% CI 0.69 to 0.93; p = 0.003) which was more evident among women aged >or=45 years at first diagnosis of breast cancer and without a family history of breast cancer (combined OR = 0.75, 95% CI 0.61 to 0.91; p = 0.004). The most common haplotype containing the c.-2265T allele also showed significant risk association for women aged >or=45 years without a family history of breast cancer (OR = 0.64, 95% CI 0.46 to 0.89; p = 0.008). CONCLUSION: This comprehensive study of BRCA1 promoter polymorphisms found four variants that altered promoter activity and with the most significant contribution from c.-2265C-->T, which could affect susceptibility to breast cancer in the Chinese population. Its significance in other populations remains to be investigated.

Efficacy of combination chemotherapy with irinotecan (CPT-11) plus capecitabine in patients with metastatic or advanced colorectal carcinoma--a dual-centre phase II study: the MAC-6.

AIMS: A phase II trial was initiated to evaluate the efficacy and toxicity of combination chemotherapy with irinotecan (CPT-11) plus capecitabine in patients with metastatic colorectal cancer. PATIENTS AND METHODS: Patients received a combination of CPT-11 plus capecitabine. CPT-11 was infused intravenously on day 1 every 2 weeks and oral capecitabine was taken twice daily for 5 days every 7 days. Efficacy and toxicities were assessed. RESULTS: Between 2004 and 2005, 43 patients were enrolled. The overall response rate was 51.35%. With a median follow-up of 13 months, the median time to progression was 10 months (95% confidence interval 7.6-12.3 months); the median survival was 15 months (95% confidence interval 13.9-16.9 months). The most common grade 3 haematological and non-haematological toxicities were neutropenia (5.4%), diarrhoea (8.1%) and hand-foot syndrome (2.7%). CONCLUSIONS: CPT-11 plus capecitabine with a 14 day cycle showed a comparable response with international phase II data with a 3 weekly regimen and was well tolerated as a first-line palliative chemotherapy in patients with metastatic colorectal cancer. The data should be interpreted with caution due to the limited sample size and should be further confirmed by a phase III randomised trial.

Hypersensitivity reactions to oxaliplatin: experience in a single institute.

BACKGROUND: A rising incidence of hypersensitivity reactions to oxaliplatin has been observed as a result of increasing clinical use. Epidemiological and clinical features of these reactions are reviewed. PATIENTS AND METHODS: Records of patients treated with a modified FOLFOX regimen from March 1999 to March 2004 were reviewed. RESULTS: One hundred and eighty patients were identified. Twenty-seven patients (15%) have been labelled as allergic to oxaliplatin, the proportion being higher among those receiving oxaliplatin in palliative second-line or above settings (19.6%) than in adjuvant or palliative first-line settings (10.2%). Some 2.2% of them developed grade 3-4 reactions. The reactions occurred after a mean (+/-SD) of 8.5 (+/-4.2) cycles (range 1-18). Among the 14 patients re-exposed to oxaliplatin, four (28.6%) developed hypersensitivity reaction, in two of whom (14.3%) reactions were grade 3-4 in severity. CONCLUSIONS: The risk of developing hypersensitivity reactions in patients receiving oxaliplatin should not be underestimated. The risk of developing potentially life-threatening hypersensitivity reactions should be explained to patients in the context of the potential benefits of such therapy. Patients receiving oxaliplatin infusion should be closely monitored. Once a patient develops hypersensitivity reaction to oxaliplatin, re-exposure should only be considered if the reaction is mild and there has been documented clinical benefit from previous doses of this agent.

The predictive value of the 1997 American Joint Committee on Cancer stage classification in determining failure patterns in nasopharyngeal carcinoma.

BACKGROUND: A retrospective analysis of treatment outcomes in patients with nasopharyngeal carcinoma (NPC) was performed in which the newly revised 1997 American Joint Committee on Cancer (AJCC) stage classification was applied and compared with the 1988 AJCC and Ho stage classifications, with emphasis on the predictive value of different staging systems in determining failure patterns in NPC. METHODS: Three hundred and twenty-four patients with newly diagnosed NPC treated between September 1989 and August 1991 and originally staged according to Ho stage classification were re-staged according to the 1988 and 1997 AJCC stage classifications. In addition to stage grouping, patients were also classified into the following prognostic categories to study the failure patterns: early disease group (T1-2N0-1), advanced local disease group (T3-4N0-1), advanced nodal disease group (T1-2N2-3), and advanced locoregional disease group (T3-4N2-3). The overall survival (OAS), relapse-free survival (RFS), local relapse-free survival, nodal relapse-free survival, and distant metastases-free survival were compared among different stage groups and prognostic categories in the three staging systems. RESULTS: In the new AJCC system, the percentages of patients with Stage I, II, III, and IV disease were 15.1%, 31.5%, 28.1%, and 25.3%, respectively, whereas most patients were classified as having Stage IV disease (65.7%) in the old AJCC system and Stage II or III disease (74.1%) in the Ho system. The 5 year OAS rates in the 1997 AJCC Stage I, II, III, and IV disease were 97.7%, 78.7%, 79.5%, and 61.4%, respectively. The corresponding 5 year RFS rates were 95.7%, 64.7%, 54.5%, and 41.1%. Using the 1997 AJCC system to define the four prognostic categories, the early disease group had the lowest incidence of relapse (27.6%) and death (18.4%), whereas the advanced locoregional disease group had the highest incidence of relapse (61.4%) and death (43.2%). Both the advanced local disease group and the advanced nodal disease group had similar rates of relapse (46.7% vs. 47.2%), but local relapse was the major cause of failure in the former group (61.8%), whereas distant metastases was the major cause in the latter group (44%). CONCLUSIONS: Using the 1997 AJCC staging system, the authors observed a better distribution of patient numbers as well as segregation of survival curves among different stage groups. Moreover, prognostic categories with distinct prognosis and failure patterns were definable by the new system, which has important implications in selecting appropriate patient treatment strategies.

Radiation recall with oxaliplatin: report of a case and a review of the literature.

Oxaliplatin is a new platinum derivative that has significant activity in patients with metastatic colorectal carcinoma. Some of these patients may have been previously treated with radiotherapy. The interaction of radiotherapy with oxaliplatin needs to be further studied. We report a patient with advanced colonic carcinoma who was treated with concomitant chemoirradiation with oxaliplatin and developed a peculiar dermnatitis in the irradiated field after being exposed to subsequent chemotherapy with oxaliplatin.

Patterns of failure after induction chemotherapy and radiotherapy for locoregionally advanced nasopharyngeal carcinoma: the Queen Mary Hospital experience.

PURPOSE: Our center contributed 183 patients to the Asian-Oceanian Clinical Oncology Association (AOCOA) multicenter randomized trial comparing induction chemotherapy (CT) followed by radiotherapy (RT) vs. RT alone in patients with locoregionally advanced undifferentiated nasopharyngeal carcinoma (NPC). In a preliminary report no difference in terms of overall survival or relapse-free survival was found between the 2 treatment arms. To study the long-term outcome and patterns of failure after CT for NPC, we analyzed our own center data for which a uniform radiation treatment protocol was adopted and a longer follow-up time was available. METHODS AND MATERIALS: Between September 1989 and August 1993, a total of 183 patients were recruited into the AOCOA randomized study from our center. Patients with newly diagnosed NPC of Ho's T3 disease, N2-N3 disease, or with neck node size of at least 3 cm were eligible. Stratification was made according to the nodal size (< or = 3 cm, >3- 6 cm, > 6 cm). Patients were randomized to receive 2-3 cycles of CT with cisplatin 60 mg/m(2) and epirubicin 110 mg/m(2) D1 followed by RT or RT alone. Four patients were excluded from the current analysis (2 died before treatment, 2 received treatment elsewhere). The remaining 179 patients were randomized to the two treatment arms, with 92 to the CT arm and 87 to the RT arm. Two patients in the CT arm had RT only, and all patients completed radiation treatment. Overall survival (OAS), relapse-free survival (RFS), local relapse-free survival (LRFS), nodal relapse-free survival (NRFS), and distant metastases-free survival (DMFS) were analyzed using Kaplan--Meier method and significance of survival curve differences calculated using log--rank test. Analysis was performed based on the intent-to-treat. RESULTS: The median follow-up was 70 months. At the time of analysis, 50% of patients in the CT arm and 61% in the RT arm had relapse, while 32% in the CT arm and 36% in the RT arm had died of the disease. The median RFS was 83 months in the CT arm and 37 months in the RT arm. The median OAS has not yet been reached for both arms. No significant differences were found for the various endpoints, although there was a trend suggesting better nodal control in the CT arm. The 5-year rates for the various endpoints in the CT arm vs. the RT arm were: 53% vs. 42% for RFS (p = 0.13), 70% vs. 67% for OAS (p = 0.68), 80% vs. 77% for LRFS (p = 0.73), 89% vs. 80% for NRFS (p = 0.079), and 70% vs. 68% for DMFS (p = 0.59). There was also no significant difference in the patterns of failure between both arms: in the CT arm, 28% of failures were local only, 13% regional only, 4% locoregional, 44% distant, and 11% mixed locoregional and distant. In the RT arm, 23% of failures were local only, 13% regional only, 11% locoregional, 43% distant, and 9% mixed locoregional and distant. CONCLUSION: Induction chemotherapy with the regimen used in the current study did not improve the treatment outcome or alter the failure patterns in patients with locoregionally advanced NPC, although there was a trend suggesting better nodal control in the combined modality arm. Alternative strategies of combining chemotherapy and radiotherapy should be tested and employed instead.

A phase II study of ifosfamide, 5-fluorouracil and leucovorin in patients with recurrent nasopharyngeal carcinoma previously treated with platinum chemotherapy.

The aim of this study was to evaluate the efficacy and toxicity of ifosfamide, 5-fluorouracil (5-FU) and leucovorin (IFL) as a second-line chemotherapy regimen in patients with recurrent undifferentiated nasopharyngeal carcinoma (NPC) previously treated with platinum/5-FU. Between June 1997 and February 1999, 18 patients were entered into the study. 3 patients had loco-regional recurrence, 12 had distant metastases and 3 had both loco-regional recurrence and distant metastases. All patients had previously received platinum/5-FU as adjuvant or palliative treatments. The IFL regimen consisting of ifosfamide 1.2 g/m(2) (with mesna), 5-FU 375 mg/m(2) and leucovorin 20 mg/m(2) for 5 days and was repeated every 21 days. The dose of ifosfamide was escalated to 1.4 and 1.6 g/m(2) in subsequent cycles according to the bone marrow toxicity, and the dose of 5-FU to 450 and 525 mg/m(2) according to the severity of mucositis. Patients received a median of 3 cycles of IFL (range: 2-6), with a median total ifosfamide dose of 21 g/m(2) (range: 13-46) and a median total 5-FU dose of 6.75 g/m(2) (range: 4.1-14.7). The median follow-up was 10 months (range: 4-25). 9 patients (50%) achieved a partial response and 1 patient (6%) achieved a complete response, with an overall response rate of 56% (95% confidence interval (CI): 32-80%). For those patients who responded to IFL, 8 had subsequent disease progression on follow-up, with a median response duration of 7.1 months (95% CI: 5.3-8.9). The median time to progression for all patients was 6.5 months (95% CI: 4.2-8.7). 12 patients are still alive with an estimated 1-year survival probability rate of 51%. Treatments were well tolerated, only 1 patient had grade 3 emesis. None of the patients had grade 3/4 anaemia, leucopenia or thrombocytopenia, although IFL was discontinued in 1 patient because of persisting thrombocytopenia. IFL is an effective second-line regimen in patients with recurrent NPC and is well tolerated with mild toxicity. Combining platinum and IFL in chemonaïve patients may further improve the overall response rate and duration and is worth investigating in future trials.

Evaluation of the benefits and risks of hormone replacement therapy.

OBJECTIVE: To review recent data on outcome of hormone replacement therapy in postmenopausal women. DATA SOURCES: Medline search of the literature and local data. STUDY SELECTION: Data on efficacy of hormone replacement and its unwanted side effects were examined. DATA EXTRACTION: Statistical data were extracted from published studies and meta-analyses. DATA SYNTHESIS: Statistical data came mainly from observational studies and not from randomised trials, and were therefore subject to bias. Overall, it would appear reasonable to say that risks for breast and endometrial cancers, as well as thromboembolism, were increased, while the risks for cardiovascular death and osteoporotic fractures were reduced by hormone replacement therapy. Locally, for every 100,000 women treated for 3 to 5 years, there may be 22 fewer cardiac deaths, 10 to 20 more cases of breast cancer, seven more cases of endometrial cancer, 10 more cases of thromboembolic disease, and slightly fewer cases of osteoporotic fracture. CONCLUSION: Reported data and risk estimates have been derived predominantly from data on white Caucasian women. Their baseline risk may be different from those of Chinese women. A low baseline risk in the local population may influence treatment results, and large-scale randomised trials are needed to give a definitive answer.

Somatic mutations in the BRCA1 gene in Chinese sporadic breast and ovarian cancer.

Inherited mutations in the BRCA1 gene confer increased susceptibility to breast and ovarian cancer. Its role in sporadic carcinogenesis is not well defined. Somatic mutations in breast cancers have not been reported and to date there are only three reports of somatic mutations in sporadic ovarian cancers. To investigate the contribution of BRCA1 mutations to sporadic breast and ovarian cancer in the Chinese population, we analysed 62 samples from Chinese women using the protein truncation test. There were 40 cases of breast cancer under age 50 and 22 cases of ovarian cancer, all unselected for family history. There was no age selection for the ovarian cancers. We found two somatic BRCA1 mutations in exon 11, one in a breast cancer and the other in an ovarian cancer, both of which result in truncated proteins. Our results indicate that somatic BRCA1 mutations, like somatic mutations in the BRCA2 gene, though very rare, can be found in both breast and ovarian cancers and support a tumor suppressor function for BRCA1 in sporadic tumors.

Locally recurrent nasopharyngeal carcinoma: treatment results for patients with computed tomography assessment.

PURPOSE: To study the treatment outcome in patients with locally recurrent nasopharyngeal carcinoma as restaged by computed tomography (CT). PATIENTS AND METHODS: One hundred forty patients with CT restaged locally recurrent nasopharyngeal carcinoma were reviewed. Patients were restaged at recurrence according to the AJCC stage classification with the following distribution: T1-T2:30%, T3:19%, T4:51%. Ninety-seven patients received reirradiation; among these 62 had external irradiation, 34 had brachytherapy, and 1 had both. Twelve patients received surgery. Thirty-one patients were treated with palliative intent and received either chemotherapy or supportive treatment only. Overall survival (OAS) and performance-adjusted survival (PAS, defined as surviving with a Karnofsky performance score [KPS] > 50) were calculated by Kaplan-Meier method. Multivariate analysis was performed using the Cox model. RESULTS: The median survival for all patients was 23.8 months. After reirradiation, the 3-yr and 5-yr OAS rates were 46% and 36%, respectively. The corresponding PAS rates were 40% and 28%. The 3-yr OAS rates for recurrent T1-2, T3, and T4 disease after reirradiation were 71%, 42%, and 30%; the corresponding 5-yr OAS rates were 57%, 42%, 17%. The 3-yr and 5-yr OAS rates in patients receiving palliative treatments only were 19% and 0%, respectively. The 3-yr OAS rate after surgery was 42%. In the multivariate analysis, older age, recurrent T3-4 disease, and palliative treatment were unfavorable factors in predicting overall survival, whereas recurrent T3-4 disease, baseline KPS < 70, and palliative treatment were unfavorable factors in predicting PAS. A high complication rate was observed after reirradiation, with 34% of patients developing neurological sequel. CONCLUSION: Aggressive treatment for locally recurrent nasopharyngeal carcinoma is warranted especially for those with disease confined to the nasopharynx. Survival after retreatment for more extensive disease remains poor but was still superior to supportive treatment only. Early diagnosis of local recurrence allows prompt administration of treatment and is associated with better outcome. Future studies should aim at improving the therapeutic ratio in the retreatment of recurrent disease especially in patients with more extensive local recurrence.

The effect of interruptions and prolonged treatment time in radiotherapy for nasopharyngeal carcinoma.

PURPOSE: The effect of interruptions and prolonged overall treatment time in radiotherapy for nasopharyngeal carcinoma and the significance of timing of interruption was investigated. METHODS AND MATERIALS: Treatment records of 229 patients treated with continuous course (CC) and 567 patients treated with split course (SC) radiotherapy for nonmetastatic NPC were reviewed. Overall treatment time without inclusion of time for boost was calculated. Treatment that extended 1 week beyond scheduled time was considered prolonged. Outcome in patients who completed treatment "per schedule" were compared with those who had "prolonged" treatment. Because of known patient selection bias between CC and SC, patients on the two schedules were analyzed separately. Multivariate analysis was performed for patients on SC. Total number of days of interruption, age, sex, T and N stage, and the use of boost were tested for the whole SC group. Analysis on the effect of timing of interruption was performed in a subgroup of 223 patients on SC who had a single unplanned interruption. Timing of interruption, either before or after the fourth week for the unplanned interruption, was tested in addition to the other variables in multivariate analysis for this subgroup of SC. RESULTS: Twenty-seven (11.8%) patients on CC and 96 (16.9%) patients on SC had prolonged treatment. Patients on SC who had prolonged treatment had significantly poorer loco-regional control rate and disease free survival when compared with those who completed radiotherapy per schedule (p = 0.0063 and 0.001, respectively, with adjustment for stage). For CC, the effect of prolonged treatment on outcome was not significant. The small number of events for patients on CC probably account for the insignificant finding. The number of days of interruption was confirmed as prognostic factor, independent of T and N stages, for loco-regional control and disease-free survival in multivariate analysis for SC. The hazard rate for loco-regional failure increased by 3.3% for each day of interruption. The timing of interruption, at the beginning or towards end of treatment, did not significantly alter outcome. CONCLUSION: Interruptions and prolonged treatment adversely affect outcome in radiotherapy for NPC and the effect of repopulation was confirmed. Every effort should be made to keep treatment on schedule and interruptions for whatever reasons should be minimized.

Current status of breast cancer in Hong Kong.

OBJECTIVE: To study the mode of presentation, the tumor, nodes, metastasis (TNM) staging and the efficacy of multimodal treatment of breast cancer among Chinese women treated in Queen Mary Hospital. METHODS: The available records of all breast cancer patients treated between January 1980 and December 1994 were reviewed. The mode of presentation, the TNM staging of the disease, estrogen receptor status and the mode of surgical and adjuvant treatment were studied. Statistical correlation was performed between the factors studied and the survival time. RESULTS: Seven hundred and one cases of breast cancer were identified. The mean age of the patients was 56.6 years (range, 20-98 years). The most common complaint was the presence of a mass which occurred in 635 (90.6%) patients and 454 (71.5%) of these patients were painless. The majority of patients had T2 tumours (51.8%) and stage II disease (59.6%), but only 86 (12.3%) patients underwent breast conservative therapy (BCT). Estrogen receptor was positive in 43% of patients. Two hundred and ninety (41.4%) patients were node positive and the mean number of involved nodes was 3.8 per patient. Adjuvant chemotherapy was given to 125 node positive patients, adjuvant tamoxifen to 188 patients and both to 63 patients. Univariate analyses of factors possibly affecting survival showed that advanced stage disease and nodal involvement were associated with a significantly lower survival time. Among the node positive patients, those with seven or more involved nodes had a shorter survival. The types of surgery and adjuvant treatment (for node positive patients) had no direct correlation with survival. CONCLUSION: Our results showed that the majority of our patients presented with a painless mass and the final outcome was determined by the tumour load at the time of presentation (TNM staging and nodal status).

Retropharyngeal lymphadenopathy in patients with nasopharyngeal carcinoma: a computed tomography-based study.

BACKGROUND: The purpose of this study was to investigate the incidence and prognostic value of retropharyngeal lymphadenopathy in nasopharyngeal carcinoma patients using contrast enhanced computed tomography (CT). METHODS: From January 1989 to December 1991, 364 patients with newly diagnosed nasopharyngeal carcinoma without distant metastasis had a baseline CT performed. All patients had radiotherapy as their primary treatment. Eighty-seven patients also received neoadjuvant chemotherapy for locally advanced disease. All patients with clinical N0 disease had prophylactic lymph node irradiation. The contrast enhanced CT given prior to all treatment was evaluated for the presence of retropharyngeal lymphadenopathy. Criteria for involved lymph nodes included a lymph node size of 10 mm or more, the presence of central necrosis within the lymph node, or the presence of a contrast enhancing rim. RESULTS: The incidence of retropharyngeal lymphadenopathy was 29.1%. A higher incidence of retropharyngeal lymph node involvement was observed in Ho's T2/T3 disease compared with T1 disease, and a higher incidence was also found in patients with cervical lymph node disease compared with those with clinical N0 disease. No significant differences in relapse free survival rates, local control rates, lymph node control rates, or distant failure rates were observed between patients with or without retropharyngeal lymphadenopathy after adjusting for T and N classifications. In 134 patients with clinical N0 disease, retropharyngeal lymphadenopathy was found in 21 patients, whereas 113 had no evidence of retropharyngeal lymphadenopathy. However, no significant difference in treatment outcome was observed between the two groups. CONCLUSIONS: Using CT imaging, the presence of retropharyngeal lymphadenopathy in patients with nasopharyngeal carcinoma does not appear to affect the prognosis. In patients with clinical N0 disease, the identification of retropharyngeal lymphadenopathy based only on CT imaging is not sufficient evidence for an N1 classification.

Breast conservation therapy for invasive breast cancer in Hong Kong: factors affecting recurrence and survival in Chinese women.

BACKGROUND: Breast conservation therapy is an established procedure for treating invasive breast cancer. However, little has been reported in the literature about its applicability in the Chinese. This study was done to find out the local recurrence and mortality rates of such therapy among Hong Kong Chinese women. In addition, the prognostic factors were also examined. METHODS: A retrospective study reviewing clinical records of breast cancer patients treated between February 1986 and September 1994 was undertaken. RESULTS: Sixty-four female patients were identified. The follow-up period ranged from 8 to 90 months with a median of 46 months. The median age at diagnosis was 51 years and 50% of patients were postmenopausal. The median tumour size was 2.5 cm and 20 patients had involved axillary lymph nodes. Ten (16%) patients developed ipsilateral breast tumour recurrence and seven underwent salvage mastectomy. Lymphovascular permeation by tumour cells was the only factor significantly associated with recurrence. Five (8%) eventually died; the 5-year disease-free and overall survival rates were 42% and 83%, respectively. Ipsilateral breast tumour recurrence correlated with a higher mortality rate whereas adjuvant treatment with either chemotherapy or tamoxifen improved the outcome. CONCLUSIONS: Breast conservation therapy is an acceptable alternative in the treatment of breast cancer in Chinese patients.

Prognostic value of paranasopharyngeal extension of nasopharyngeal carcinoma. A significant factor in local control and distant metastasis.

BACKGROUND: This study was conducted to evaluate the prognostic value of paranasopharyngeal extension in local control and distant metastasis in patients with nasopharyngeal carcinoma. METHODS: Three hundred and sixty-four patients with newly diagnosed nasopharyngeal carcinoma without distant metastasis were reviewed. Patients were staged according to Ho's staging system. Using a semiquantitative method, tumor extension into the paranasopharyngeal space was graded as: 0: no extension; 1: extension to the retrostyloid space; 2: extension to the prestyloid space; and 3: extension to the anterior part of the masticator space. All patients received radiotherapy as primary treatment. Median follow-up time was 45 months (range, 4.7 to 76.5 months). Relapse free, local relapse free, and distant metastasis free survival were estimated using the Kaplan-Meier method. Cox regression was also performed to adjust for prognostic factors. RESULTS: The incidence of paranasopharyngeal extension was high (72.5%). Of these patients, 65.5% had Grade 2 or 3 extension. The 5-year relapse free survival rates for Grade 0, 1, 2, and 3 extension were 76%, 70%, 46%, and 43%, respectively. The main difference was between Grade 0/1 and Grade 2/3 extension, the latter having a lower 5-year local control rate (86% in Grade 0/1 vs. 72% in Grade 2/3; P < 0.0001) and distant metastasis free survival rate (87% in Grade 0/1 vs. 68% in Grade 2/3; P = 0.0002). Multivariate analysis showed that Grade 2/3 paranasopharyngeal extension was an independent factor in predicting overall relapse, local relapse, and distant metastasis. Advanced T classification (T3) was another independent factor in predicting overall and local relapse, whereas advanced N classification (N3) was another independent factor in predicting overall relapse and distant metastasis. CONCLUSIONS: Extensive paranasopharyngeal extension (Grade 2/3) was an independent prognostic factor associated with poorer treatment outcome, both in local control and distant metastasis. Ho's T2 disease should be further subclassified into T2a and T2b, which include Grade 0/1 and Grade 2/3 paranasopharyngeal disease, respectively.

The antiemetic efficacy of tropisetron plus dexamethasone as compared with conventional metoclopramide-dexamethasone combination in Orientals receiving cisplatin chemotherapy: a randomized crossover trial.

1. We report a single-blind randomized crossover trial comparing the efficacy of tropisetron plus dexamethasone (TROPDEX) vs conventional combination of metoclopramide, dexamethasone and diphenhydramine (METDEX) in prevention of acute and delayed vomiting in Chinese patients receiving high dose cisplatin. 2. Thirty-six consecutive patients with nasopharyngeal carcinoma were entered into the study, all received cisplatin at a dose range of 60-100 mg/m2. Patients were randomized in the sequence of antiemetic regimens used in two consecutive cycles. 3. The TROPDEX regimen consisting of tropisetron 5 mg i.v. and dexamethasone 20 mg i.v. given on day 1 of chemotherapy, followed by oral maintenance with tropisetron 5 mg daily and dexamethasone 4 mg twice daily from day 2 to 6. The METDEX regimen consisting of metoclopramide 1 mg kg-1 i.v., dexamethasone 20 mg i.v. and diphenhydramine 25 mg i.v. given before chemotherapy and then 2 hourly for two more doses on day 1, followed by oral metoclopramide 20 mg 6 hourly from day 2 to 6. 4. Complete control of acute vomiting was observed in 64% of patients with TROPDEX as compared with 14% with METDEX (P < 0.01). While complete plus major control of acute vomiting was observed in 84% with TROPDEX as compared with 58% with METDEX. The mean vomiting episodes on day 1 were 1.4 with TROPDEX as compared with 3.5 with METDEX (P < 0.01). There was, however, no significant difference between the two regimens in the control of delayed vomiting. 5. When patients randomized to TROPDEX in the second cycle were compared with those with TROPDEX in the first cycle, the antiemetic efficacy was reduced, with mean acute vomiting episodes of 2 in the former compared with 0.8 in the latter (P < 0.01). 6. The most common adverse effect observed was headache in TROPDEX (27%) and dizziness in METDEX (40%). 7. In conclusion, the antiemetic regimen TROPDEX is effective in Chinese patients receiving high dose cisplatin chemotherapy and is well tolerated. It is better than conventional METDEX regimen in the control of acute vomiting, but not in the control of delayed vomiting.

Radiotherapy for nasopharyngeal carcinoma: shielding the pituitary may improve therapeutic ratio.

PURPOSE: Nasopharyngeal carcinoma (NPC) is well known for its invasiveness and erosion of the base of the skull is not uncommon. Before the advent of computed tomography, the evaluation of the base of the skull was by plain radiography. Because of the low sensitivity of these investigations, traditional teaching has included the sphenoid sinus in the volume of irradiation. Increase in longevity of patients allows the manifestation and documentation of the long-term sequelae of irradiating the hypothalamic-pituitary axis and the temporal lobes. This study is an attempt to evaluate whether the hypothalamic-pituitary axis can be shielded from the target volume in a proportion of NPC patients. METHODS AND MATERIALS: One hundred fifty-two NPC patients with no evidence of erosion of the base of the skull and sphenoid, nor extension to the nasal fossa and ethmoid sinuses were randomized to receive standard radiotherapy covering the whole sphenoid sinus or radiotherapy using a modified technique that shields the pituitary and the anterior part of the hypothalamus. This modified technique also shields a large part of the lower temporal lobes that are otherwise covered by standard treatment portals. The characteristics and treatment of the two subgroups of patients were otherwise comparable. RESULTS: At a median follow-up of 31.5 months, the tumor control between the two subgroups of patients were comparable (p = 0.3928). However, 8 of the 71 patients in the unshielded group had developed symptomatic neuroendocrine complications, while none of the other group did (p = 0.0061). Two patients developed secondary hypothyroidism, one patient developed oligomenorrhoea associated with raised prolactin, and five patients developed temporal lobe necrosis. CONCLUSIONS: The protective effect on neuroendocrine complication of this shield was demonstrated at median follow-up of 31.5 months, and the local control was not jeopardized. Modification of treatment technique as presently described, which is applicable to one-third of NPC patients to improve the therapeutic ratio, is recommended for general use.

Magnetic resonance imaging in the clinical diagnosis of late temporal lobe necrosis following radiotherapy for nasopharyngeal carcinoma.

Magnetic resonance imaging (MRI) and computed tomography (CT) were performed on 13 patients with clinical features of late temporal lobe damage following radical radiotherapy for nasopharyngeal carcinoma, and their results compared. MRI was undoubtedly superior in sensitivity--revealing areas of prolonged T2 relaxation time in the inferior portions of the temporal lobes in all patients, while CT failed to show any gross abnormalities in seven. In patients with large lesions well-depicted on CT, the corresponding MRI changes were comparable in shape and extent. But MRI gave an additional sign for the presence of liquefactive necrosis, and revealed lesions in the contralateral lobes in two out of three patients with unilateral CT changes. Besides obvious improvement in detection rate, the contribution of MRI to the better selection of treatment protocols, and to the understanding of the pathological process are discussed.