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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. [ABSTRACT FROM AUTHOR]

Background: We would like to investigate the if IMRT produced better target coverage and dose sparing to adjacent normal structures as compared with 3-dimensional conformal radiotherapy (3DCRT) and lateral opposing fields (LOF) for patients with Graves' ophthalmopathy treated with retro-orbital irradiation., Methods: Ten consecutive patients diagnosed with Graves' ophthalmopathy were prospectively recruited into this study. An individual IMRT, 3DCRT and LOF plan was created for each patient. Conformity index (CI), homogeneity index (HI) and other dosimetric parameters of the targets and organs-at-risk (OAR) generated by IMRT were compared with the other two techniques., Results: Mann-Whitney U test demonstrated that CI generated by IMRT was superior to that produced by 3DCRT and LOF (p=0.005 for both respectively). Similarly HI with IMRT was proven better than 3DCRT (p=0.007) and LOF (p=0.005). IMRT gave rise to better dose sparing to some OARs including globes, lenses and optic nerves as compared with 3DCRT but not with LOF., Conclusions: IMRT, as compared with 3DCRT and LOF, was found to have a better target coverage, conformity and homogeneity and dose sparing to some surrounding structures, despite a slight increase but clinically negligible dose to other structures. Dosimetrically it might be a preferred treatment technique and a longer follow up is warranted to establish its role in routine clinical use.

Purpose: We wanted to investigate dosimetric parameters that would predict radiation-induced acute nausea and vomiting in intensity-modulated radiation therapy (IMRT) for undifferentiated carcinoma of the nasopharynx (NPC)., Methods and Materials: Forty-nine consecutive patients with newly diagnosed NPC were treated with IMRT alone in this prospective study. Patients receiving any form of chemotherapy were excluded. The dorsal vagal complex (DVC) as well as the left and right vestibules (VB-L and VB-R, respectively) were contoured on planning computed tomography images. A structure combining both the VB-L and the VB-R, named VB-T, was also generated. All structures were labeled organs at risk (OAR). A 3-mm three-dimensional margin was added to these structures and labeled DVC+3 mm, VB-L+3 mm, VB-R+3 mm, and VB-T+3 mm to account for physiological body motion and setup error. No weightings were given to these structures during optimization in treatment planning. Dosimetric parameters were recorded from dose-volume histograms. Statistical analysis of parameters' association with nausea and vomiting was performed using univariate and multivariate logistic regression., Results: Six patients (12.2%) reported Grade 1 nausea, and 8 patients (16.3%) reported Grade 2 nausea. Also, 4 patients (8.2%) complained of Grade 1 vomiting, and 4 patients (8.2%) experienced Grade 2 vomiting. No patients developed protracted nausea and vomiting after completion of IMRT. For radiation-induced acute nausea, V40 (percentage volume receiving at least 40Gy) to the VB-T and V40>=80% to the VB-T were predictors, using univariate analysis. On multivariate analysis, V40>=80% to the VB-T was the only predictor. There were no predictors of radiation-induced acute vomiting, as the number of events was too small for analysis., Conclusions: This is the first study demonstrating that a V40 to the VB-T is predictive of radiation-induced acute nausea. The vestibules should be labeled as sensitive OARs, and weightings should be considered for dose sparing during optimization in the treatment planning of IMRT., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: 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., Methods: 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., Findings: 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., Interpretation: 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., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Background and Purpose: To evaluate the therapeutic benefits by adding chemotherapy (+C) and/or accelerated-fractionation (AF) for patients with T3-4N0-1M0 nasopharyngeal carcinoma., Materials and Methods: From 1999 to 2004, 189 eligible patients were randomized to one of four treatment groups (CF/CF+C/AF/AF+C). The number of fractions/week was 5 for the CF groups and 6 for the AF groups. Patients in the +C groups were given concurrent cisplatin plus adjuvant cisplatin and fluorouracil., Results: The AF+C group achieved significantly higher failure-free rate (88% at 5-year) than the CF group (63%; p=0.013), the AF group (56%; p=0.001) and the CF+C group (65%; p=0.027). As compared with CF alone, the increase in late toxicity was statistically insignificant (36% vs. 20%; p=0.25). Deaths due to cancer progression decreased (7% vs. 33%; p=0.011) but deaths due to incidental causes increased (9% vs. 2%; p=0.62). Improvement in overall survival reached borderline significance (85% vs. 66%; p=0.058)., Conclusions: Concurrent-adjuvant chemotherapy combined with AF significantly reduced failure and cancer-specific deaths. Although the increase in major late toxicity and incidental deaths were statistically insignificant, a subtle increase in non-cancer deaths narrowed the overall survival gain., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

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.

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.

Background: This single-center, phase II study assessed the safety/tolerability and initial efficacy of gefitinib in patients with nasopharyngeal carcinoma (NPC) pretreated with platinum-based chemotherapy., Methods: Patients with recurrent and metastatic NPC who had treatment failure with at least 2 lines of chemotherapy including platinum were given gefitinib at a fixed dose of 250 mg daily. Treatment was continued until the patient experienced unacceptable side effects or disease progression., Results: Nineteen patients were enrolled, having had treatment failure with a median of 2 chemotherapy regimens. Treatment was well tolerated, and only grades 1 to 2 adverse events were observed. None of the patients achieved partial or complete response. Median time-to-progression was 4 months, and median overall survival was 16 months., Conclusion: Gefitinib was well tolerated, but the response rate was poor in this heavily pretreated study population, and its use in NPC is not recommended outside the context of clinical trial.

Background: Capecitabine monotherapy had activity in recurrent/metastatic nasopharyngeal carcinoma (NPC) as demonstrated previously in a small pilot study. We conducted a retrospective review of patients who received capecitabine for recurrent and metastatic NPC to further evaluate its clinical benefits., Methods: Forty-nine patients with recurrent and metastatic NPC received capecitabine at a dose of 1-1.25 G/m(2) twice daily for 14 days in 3-week cycles. Disease sites were locoregional in 29%, distant in 45% and locoregional plus distant in 26%. All except one had prior platinum-based chemotherapy for relapse or as adjunctive treatment. Median follow-up was 10 months (range: 3-41)., Results: Treatment was generally well tolerated. Hand-foot syndrome was common and occurred in 86% (25% Grade 3). Grade 3 hematological toxicity occurred in 6%. Partial response rate was 31% (95% CI: 18%, 44%) and complete response rate was 6% (95% CI: 0%, 13%), for an overall response rate of 37% (95% CI: 23%, 50%). Median time-to-progression was 5 months and median survival was 14 months. One- and two-year survival rates were 54 and 26%, respectively. Significantly better survival was observed in patients treated for locoregional recurrence and those with severe hand-foot syndrome., Conclusions: Capecitabine has single agent activity in NPC and severe hand-foot syndrome predicts favorable outcome. Based on our experience, capecitabine monotherapy should be considered in patients with recurrent/metastatic NPC.

Context: MicroRNAs have potential as diagnostic biomarkers and therapeutic targets in cancer. No study has evaluated the association between microRNA expression patterns and colon cancer prognosis or therapeutic outcome., Objective: To identify microRNA expression patterns associated with colon adenocarcinomas, prognosis, or therapeutic outcome., Design, Setting, and Patients: MicroRNA microarray expression profiling of tumors and paired nontumorous tissues was performed on a US test cohort of 84 patients with incident colon adenocarcinoma, recruited between 1993 and 2002. We evaluated associations with tumor status, TNM staging, survival prognosis, and response to adjuvant chemotherapy. Associations were validated in a second, independent Chinese cohort of 113 patients recruited between 1991 and 2000, using quantitative reverse transcription polymerase chain reaction assays. The final date of follow-up was December 31, 2005, for the Maryland cohort and August 16, 2004, for the Hong Kong cohort., Main Outcome Measures: MicroRNAs that were differentially expressed in tumors and microRNA expression patterns associated with survival using cancer-specific death as the end point. RESULTS Thirty-seven microRNAs were differentially expressed in tumors from the test cohort. Selected for validation were miR-20a, miR-21, miR-106a, miR-181b, and miR-203, and all 5 were enriched in tumors from the validation cohort (P < .001). Higher miR-21 expression was present in adenomas (P = .006) and in tumors with more advanced TNM staging (P < .001). In situ hybridization demonstrated miR-21 to be expressed at high levels in colonic carcinoma cells. The 5-year cancer-specific survival rate was 57.5% for the Maryland cohort and was 49.5% for the Hong Kong cohort. High miR-21 expression was associated with poor survival in both the training (hazard ratio, 2.5; 95% confidence interval, 1.2-5.2) and validation cohorts (hazard ratio, 2.4; 95% confidence interval, 1.4-3.9), independent of clinical covariates, including TNM staging, and was associated with a poor therapeutic outcome., Conclusions: Expression patterns of microRNAs are systematically altered in colon adenocarcinomas. High miR-21 expression is associated with poor survival and poor therapeutic outcome.

Background: Limited local failure of nasopharyngeal carcinoma (NPC) can often be salvaged by reirradiation using different techniques. Both gold grain implantation (GGI) and stereotactic radiosurgery (SRS) have been used as salvage treatment of NPC but the relative efficacy of these two treatments is not known., Methods and Materials: A total of 74 patients with local NPC failure were included in this retrospective analysis. Of these patients, 37 underwent SRS (median dose, 12.5 Gy) and 37 split-palatal GGI at a dose of 60 Gy. The two groups were individually matched for prognostic factors, except for tumor volume. The median follow-up was 42 months., Results: Local control was better in the GGI group. The 3-year local failure-free rate was 77.9% for the GGI group compared with 68.3% for the SRS group. However, the difference was not statistically significant (p = 0.098). In the subgroup with a tumor volume of

Background: Radiotherapy (RT) promises optimistic results in the treatment of nasopharyngeal cancer (NPC). The objective of the current study was to map out prospectively the impact of NPC and RT on patients from diagnosis to 1 year posttreatment., Methods: For this study, 67 Chinese patients (46 men and 21 women) with newly diagnosed stage I or II NPC who received primary RT were recruited. Physical and psychosocial adjustments were measured by using the Rotterdam Symptom Checklist, Beck Anxiety Inventory, Beck Depression Inventory, Perceived Stress Scale, and the 36-item Short-Form Health Survey (SF-36). Semistructured clinical interviews were conducted at bimonthly intervals from pre-RT to 1 year post-RT., Results: Physical and psychosocial adjustments were poorest from pre-RT to the end of RT. Rapid improvements in all areas were noted in the first 2 months post-RT and reached a plateau at around the 6th month. At 1 year, except for physical symptoms and perceived stress, patient measures recovered to their pre-RT levels. At 1 year, patients had more physical complaints (P < .001) but less perceived stress (P = .002). The percentage of patients who expressed fear of dying dropped from 28% pre-RT to 2% at 1 year. However, patients who expressed "fear of the worst happening" increased from 51% pre-RT to 57% at 1 year., Conclusions: Different periods in treatment of NPC imposed different psychosocial demands on patients. The current results indicated that the period from diagnosis to 2-month post-RT was a high-risk period both physically and emotionally. After treatment, most patients showed resilience despite persistent side effects of RT and successfully resumed their pretreatment level of functioning by the end of the year. Despite resuming a normal or near-normal living, patients still noted a subdued fear of recurrence., ((c) 2007 American Cancer Society.)

Background: Stereotactic radiosurgery has been employed as a salvage treatment of local failures of nasopharyngeal carcinoma (NPC). To identify patients that would benefit from radiosurgery, we reviewed our data with emphasis on factors that predicted treatment outcome., Patients and Methods: A total of 48 patients with local failures of NPC were treated by stereotactic radiosurgery between March 1996 and February 2005. Radiosurgery was administered using a modified linear accelerator with single or multiple isocenters to deliver a median dose of 12.5 Gy to the target periphery. Median follow-up was 54 months., Results: Five-year local failure-free probability after radiosurgery was 47.2% and 5-year overall survival rate was 46.9%. Neuroendocrine complications occurred in 27% of patients but there were no treatment-related deaths. Time interval from primary radiotherapy, retreatment T stage, prior local failures and tumor volume were significant predictive factors of local control and/or survival whereas age was of marginal significance in predicting survival. A radiosurgery prognostic scoring system was designed based on these predictive factors. Five-year local failure-free probabilities in patients with good, intermediate and poor prognostic scores were 100%, 42.5%, and 9.6%. The corresponding five-year overall survival rates were 100%, 51.1%, and 0%., Conclusion: Important factors that predicted tumor control and survival after radiosurgery were identified. Patients with good prognostic score should be treated by radiosurgery in view of the excellent results. Patients with intermediate prognostic score may also be treated by radiosurgery but those with poor prognostic score should receive other salvage treatments.

Purpose: Induction chemotherapy has not been shown to improve survival in nasopharyngeal carcinoma (NPC) in Phase III trials. To evaluate the effect of induction chemotherapy in NPC further, we performed subgroup analysis of two Phase III trials according to the T and N stage., Methods and Materials: Data from two phase III trials comparing cisplatin/epirubicin or cisplatin/bleomycin/5-fluorouracil followed by radiotherapy (RT) vs. RT alone in NPC were pooled together for analysis. Patients were stratified into four subgroups according to the 1997 American Joint Committee on Cancer T and N stage: T1-T2N0-N1, Group 1 (early-stage disease); T1-T2N2-N3, Group 2 (advanced N disease); T3-T4N0-N1, Group 3 (advanced T stage); and T3-T4N2-N3, Group 4 (advanced T and N disease). Group 1 consisted entirely of patients with Stage IIB disease. A total of 784 patients were included for analysis on an intent-to-treat basis. The median follow-up for the surviving patients was 67 months., Results: No significant differences in overall survival, locoregional failure-free, or distant metastasis-free rates were observed between the combined and RT arms in Groups 2 to 4. Significant differences in the overall survival and distant metastasis-free rates were observed only in Group 1, favoring the combined chemotherapy and RT arm. The 5-year overall survival rate was 79% in the combined arm and 67% in the RT-alone arm (p = 0.048). The corresponding 5-year distant metastasis-free rates were 86% and 74% (p = 0.0053)., Conclusions: Our results have shown that patients in Group 1, with early-stage NPC treated by RT alone, had relatively poor survival because of distant metastases. The observation of improved outcomes in this subgroup after the addition of induction chemotherapy has not been previously reported and warrants additional investigation.

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.

Background and Purpose: To evaluate the treatment outcome in patients with locally recurrent nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT)., Materials and Methods: Between October 2001 and May 2004, 31 patients with locally recurrent NPC received re-irradiation using IMRT. The rT classification distribution was 3 for rT1, 5 for rT2, 9 for rT3, and 14 for r T4. Median time from first course of radiotherapy to re-irradiation was 51 months. IMRT was performed using step-and-shoot method with nine 4-6 MV photon fields and median prescribed dose was 54 Gy (range: 50-60 Gy). Additional treatments included cisplatin-based induction chemotherapy in 68% and radiosurgery boost with a single dose which ranged from 8.5 to 12.5 Gy in 32%. Median follow-up time was 11 months., Results: After re irradiation, 58% of patients had complete regression of primary tumor. One-year loco-regional progression-free, distant metastasis-free and overall survival rates were 56, 90, and 63%, respectively. Significantly better 1-year local progression-free rate was observed in rT1-3 than r T4 tumor (100 vs. 35%). Grade 3 late toxicities, mostly ototoxicity/cranial neuropathy, occurred in six patients (19%). One-year actuarial rates of late toxicities were 70% for all grades and 25% for Grade 3., Conclusion: Our preliminary results showed that good control of rT1-3 NPC can be achieved using IMRT with a dose between 50 and 60 Gy, whereas the outcome for r T4 tumor remained poor. Late toxicities were common but incidence of severe toxicities was relatively low.

Objectives: Patients with advanced local recurrence of nasopharyngeal carcinoma (NPC) have a poor prognosis. Retreatment by external radiotherapy is frequently the only option but results are usually poor. This study was conducted to evaluate the benefits of adding induction chemotherapy with cisplatin and gemcitabine before reirradiation for locally recurrent NPC., Methods: Twenty patients with locally recurrent NPC not amenable to brachytherapy or surgery were enrolled between September 2001 and October 2003. The T stage distribution at recurrence was 5% rT2, 30% rT3, and 65% rT4. Induction chemotherapy consisted of cisplatin 40 mg/m2 and gemcitabine 1.25 g/m days 1 and 8 for 3 times per week for 3 cycles, followed by reirradiation using intensity-modulated radiotherapy., Results: A total of 58 chemotherapy cycles were administered to patients and most received 3 cycles. Hematological toxicities were mild, with grade 3 and 4 neutropenia in 55% and 5% of patients, respectively, and grade 3 thrombocytopenia in 5%. After chemotherapy, 15 patients achieved partial response (75%). Seventeen patients received external reirradiation and one had radiosurgery after chemotherapy. Severe acute radiation toxicities were uncommon. After a median follow-up of 14.5 months, 55% of patients had locoregional progression and 45% had died. The 1-year locoregional progression-free, local progression-free, and overall survival rates were 63%, 68%, and 80%, respectively. In patients with external reirradiation, the 1-year local progression-free and overall survival rates were 75% and 88%. Patients with rT2-3 stage had significantly better 1-year local control rates than those with rT4 stage (100% versus 52%)., Conclusions: The combination cisplatin and gemcitabine is active and well-tolerated in locally recurrent NPC. The current approach of using induction chemotherapy before reirradiation may improve the outcome of patients with advanced local recurrence and merits further investigation.

Purpose: This randomized study compared the results achieved by concurrent chemoradiotherapy (CRT) versus radiotherapy (RT) alone for nasopharyngeal carcinoma (NPC) with advanced nodal disease., Patients and Methods: 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., Results: 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)., Conclusion: 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.

To evaluate the efficacy and safety of docetaxel and cisplatin as first-line chemotherapy in patients with metastatic nasopharyngeal carcinoma (NPC). Nineteen previously untreated metastatic NPC patients received one to six cycles of docetaxel and cisplatin. Fifteen patients received at least three cycles. The starting dose was 75 mg/m2 every three weeks for both drugs in 15 patients, and 60 mg/m2 for both drugs in four patients. All patients were included in toxicity and survival analysis, and 16 patients were evaluable for response. Median follow-up time was 11.6 months. Hematological toxicity was severe with Grade 4 neutropenia in 78.9% patients and 51.3% cycles. Febrile neutropenia occurred in 42% patients and 12.5% cycles, with two septic deaths in the population treated with 75 mg/m2. Patients treated with a dose subsequently reduced to 60 mg/m2 had a lower incidence of Grade 4 neutropenia and no incidence of neutropenic fever/sepsis. Overall response rate was 62.5%, with a 95% confidence interval of 35-85%. Partial and complete response rates were 56.3% and 6.3%, respectively. Median time to progression was 5.6 months and median survival was 12.4 months. Three patients (15.6%) survived >2 years following chemotherapy. The combination of docetaxel and cisplatin is active in metastatic NPC. The dose of 60 mg/m2 for both drugs without colony-stimulating factor support should be further evaluated as a high incidence of febrile neutropenia was observed with 75 mg/m2 dose.

Background: 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., Methods: 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., Results: 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., Conclusions: 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., (2005 Wiley Periodicals, Inc.)

Background: Xerostomia is a uniform complication after radiotherapy (RT) for nasopharyngeal carcinoma (NPC). Dosimetric studies suggested that intensity-modulated RT (IMRT) can spare part of the parotid glands from high-dose radiation. Disease control and salivary function after IMRT for early-stage NPC was studied prospectively., Methods: Thirty-three patients with T1,N0-N1,M0 NPC were treated with IMRT from 2000 to 2002. The prescribed dose was 68-70 grays (Gy) in 34 fractions to gross tumor volume, 64-68 Gy to the planning target volume, and 70 Gy to enlarged cervical lymph nodes. Nineteen patients had stimulated whole salivary (SWS) flow assessment and stimulated parotid salivary (SPS) flow assessment at baseline and at 2 months, 6 months, 12 months, 18 months, and 24 months after the completion of IMRT., Results: At a median follow-up of 2 years, only 1 neck failure was observed. The 2-year and 3-year local control, distant metastases-free, and overall survival rates all were 100%. The lymph node control and progression-free survival rates were 100% at 2 years and 92.3% at 3 years, respectively. The average mean dose to the parotid gland was 38.8 Gy. The SWS and SPS flow showed continuous recovery: 60% and 47.1% of patients recovered at least 25% of their baseline SPS flow and SWS flow, respectively, at 1 year after completion of IMRT, and the proportions rose to 85.7% and 71.4%, respectively, by 2 years. The pH and buffering capacity of saliva also improved with time., Conclusions: Parotid-sparing IMRT achieved good locoregional control, and there was continuous recovery of salivary flow, pH, and buffering capacity in the first 2 years after IMRT in patients with NPC., ((c) 2004 American Cancer Society.)

Purpose: To study the efficacy of concurrent chemoradiotherapy (CRT) and adjuvant chemotherapy (AC) for nasopharyngeal carcinoma (NPC)., Patients and Methods: Patients with Ho's stage T3 or N2/N3 NPC or neck node > or = 4 cm were eligible. Patients were randomly assigned to have radiotherapy (RT) or CRT with uracil and tegafur and to have AC or no AC after RT/CRT. AC comprised alternating cisplatin, fluorouracil, vincristine, bleomycin, and methotrexate for six cycles. There were four treatment groups: A, RT; B, CRT; C, RT and AC; D, CRT and AC. For CRT versus RT, groups B and D were compared with groups A and C. For AC versus no AC, groups C and D were compared with groups A and B., Results: Three-year failure-free survival (FFS) and overall survival (OS) for CRT versus RT were 69.3% versus 57.8% and 86.5% versus 76.8%, respectively (P =.14 and.06; n = 110 v 109). Distant metastases rate (DMR) was significantly reduced with CRT (14.8% v 29.4%; P =.026). Locoregional failure rates (LRFR) were similar (20% v 27.6%; P =.39). Three-year FFS and OS for AC versus no AC were 62.5% versus 65% and 80.4% versus 83.1%, respectively (P =.83 and.69; n = 111 v 108). DMR and LRFR were not reduced with AC (P =.34 and.15, respectively). Cox model showed CRT to be a favorable prognostic factor for OS (hazard ratio, 0.42; P =.009)., Conclusion: An improvement in OS with CRT was observed but did not achieve statistical significance. The improvement seemed to be associated with a significant reduction in DMR. AC did not improve outcome.

Purpose: A retrospective study was performed to correlate the expression of epidermal growth factor receptor (EGFR) with treatment outcome in advanced stage nasopharyngeal carcinoma (NPC)., Methods and Materials: The study population comprised 54 of 92 patients with American Joint Committee on Cancer Stage III-IV NPC with sufficient pretreatment tumor biopsy specimens for study. Immunohistochemical staining was performed to evaluate the extent and intensity of EGFR expression. All patients were treated by induction chemotherapy with two to three cycles of cisplatin 60 mg/m(2) and epirubicin 110 mg/m(2) every 3 weeks followed by radiotherapy. The median follow-up time was 52 months for all patients and 99 months for surviving patients., Results: EGFR expression was present in 89% of cases. EGFR intensity was negative in 11%, weak in 43%, moderate in 13%, and strong in 33%. The EGFR extent was <5% in 15%, > or =5% but <25% in 13%, and > or =25% in 72%. No correlation was found between EGFR expression and T stage, N stage, stage group, nodal size, gender, and age. No statistically significant differences in chemotherapy response rates were found in patients with different EGFR intensity and extent. EGFR extent > or =25% was associated with a significantly poorer treatment outcome. The 5-year disease-specific survival, relapse-free survival, locoregional relapse-free, and distant metastasis-free rate in patients with EGFR extent > or =25% was 48%, 36%, 60%, and 55%, respectively. The corresponding rates in patients with EGFR extent <25% were 86%, 80%, 93%, and 86%. The differences were all statistically significant, except for distant metastasis. No statistically significant differences in relapse-free and disease-specific survival rates were found among patients with differing EGFR intensity. In multivariate analysis, EGFR extent was the only independent factor that predicted for disease relapse, locoregional failure, and cancer death., Conclusion: Our study results showed that EGFR expression was common in advanced stage NPC, and the expression did not correlate with tumor or nodal stage. Correlative analysis showed that EGFR extent was a strong, independent prognostic factor that determined locoregional control, relapse-free survival, and disease-specific survival in Stage III-IV NPC treated with induction chemotherapy and radiotherapy. Our findings suggest that EGFR expression status can identify a subgroup of patients within advanced stage disease that will have a poor outcome after induction chemotherapy and radiotherapy. Whether this patient subgroup will benefit from an alternate treatment strategy and anti-EGFR-targeted treatment requires additional studies.

Purpose: To determine whether the tumor volume can predict the treatment outcome in early-stage nasopharyngeal carcinoma (NPC) treated by radiotherapy alone., Methods and Materials: The pretreatment CT scans of 116 patients with American Joint Committee on Cancer Stage I-II NPC treated by radiotherapy alone were retrospectively reviewed. The clinician outlined the tumor extent. The primary tumor volume (PTV) and nodal volume (NV) were then calculated by a summation-of-areas technique. The PTV and NV were correlated with locoregional control, distant failure, and survival. The median follow-up time was 105 months., Results: Patients with Stage I disease had a 5-year locoregional control rate of 95% and a disease-specific survival (DSS) rate of 97%; for Stage II disease, the corresponding rates were 81% and 79%. The PTV ranged from 1.3 to 75.5 cm3 (median, 12.6 cm3), with substantial overlap between T1 and T2 disease. The NV ranged from 0 to 35.4 cm(3). Patients with a PTV >15 cm3 had significantly worse local control (5-year control rate, 82% vs. 93%; p = 0.033), but no statistically significant difference was noted in survival (5-year DSS rate, 83% vs. 89%; p = 0.30). The difference in local control was mainly seen in those with T2 disease. Patients with NV >4 cm3 had a greater distant failure rate (5-year distant metastasis-free rate, 72% vs. 90%; p = 0.011) and worse survival (5-year DSS rate, 76% vs. 94%; p = 0.0038). Nodal control was excellent with no difference between a NV of < or =4 cm3 and a NV of >4 cm3 (5-year control rate, 97% vs. 100%). The survival rate was worst in patients with a PTV >15 cm3 and a NV >4 cm3 (5-year DSS rate, 68%) and best in those with a PTV of < or =15 cm3 and a NV of < or =4 cm3 (5-year DSS rate, 92%). Multivariate analysis, however, showed that only parapharyngeal extension (T2b) and N1 stage were independent factors that predicted locoregional control and survival, and N1 stage was the only factor that predicted distant failure., Conclusion: The pretreatment tumor volume has a limited prognostic value in early-stage NPC compared with the usual T and N classification, with Stage T2b and N1 as independent factors that predicted treatment outcome. Within T2 disease, the estimation of tumor volume may identify a subgroup of patients with a greater risk of local failure that warrants more aggressive treatment.

Background: To evaluate the toxicity and efficacy of concurrent chemoirradiation with cisplatin followed by adjuvant ifosfamide, 5-fluorouracil and leucovorin in patients with stage IVb nasopharyngeal carcinoma (NPC) PATIENTS AND METHODS: Between October 1998 and August 2001, 35 Chinese patients with stage IVb NPC (N3a:12, N3b:23) were treated with by concurrent chemoirradiation using cisplatin 100 mg/m2 on days 1, 22, and 43 of radiotherapy, followed by adjuvant chemotherapy with 1.4 g/m2, ifosfamide, 450 mg/m2 5-fluorouracil, and 20 mg/m2 leucovorin daily for 5 days and repeated every 3 weeks for three cycles. Radiotherapy was given using standard fractionation at 2 Gy/day to a total of 68 Gy to the nasopharynx and 66 Gy to the neck., Results: All patients completed the prescribed radiotherapy. Twenty-three patients (66%) completed all scheduled cycles of chemotherapy. The compliance rate for concurrent and adjuvant chemotherapy was 71% and 80%, respectively. Grade 3 mucositis occurred in 37%, and grade 3 dermatitis occurred in 11.5% during radiotherapy. Grade 3 neutropenia occurred in 17% during concurrent chemotherapy, and grade 3-4 neutropenia occurred in 48.5% during adjuvant chemotherapy. There were no treatment-related deaths. With a median follow-up of 31 months, the 3-year relapse-free rate was 60%, and the 3-year overall survival rate was 74%. Locoregional control was excellent, with a 3-year local and nodal relapse-free rate of 91% and 83%, respectively. Eleven patients (31%) had developed distant metastases, and the 3-year distant metastasis-free rate was 66%., Conclusions: The chemotherapy regimen tested is practical with an acceptable compliance rate. Despite having a more advanced stage disease, the observed outcome of our patients seems to be comparable with other series using platinum-based adjuvant chemotherapy. Further investigation to confirm the benefit of using the study regimen in advanced stage NPC is warranted., (Copyright 2004 Wiley Periodicals, Inc. Head Neck 26: 118-126, 2004)

Background: The objective of this study was to review the long-term treatment outcome of patients with American Joint Committee on Cancer (AJCC) 1997 Stage I-II nasopharyngeal carcinoma (NPC) who were treated with radiotherapy alone., Methods: One hundred forty-one patients with NPC had AJCC 1997 Stage I-II disease (Stage I NPC, 50 patients; Stage II NPC, 91 patients) after restaging and were treated with radiotherapy alone between September 1989 and August 1991. Fifty-seven patients had lymph node disease, and the median greatest lymph node dimension was 3 cm. The median dose to the nasopharynx was 65 grays. The median follow-up was 82 months (range, 4-141 months)., Results: Patients who had Stage I disease had an excellent outcome after radiotherapy. The 10-year disease specific survival, recurrence free survival (RFS), local RFS, lymph node RFS, and distant metastasis free survival rates were 98%, 94%, 96%, 98%, and 98%, respectively. Patients who had Stage II disease had a worse outcome compared with patients who had Stage I disease: The corresponding 10-year survival rates were 60%, 51%, 78%, 93%, and 64%. The differences all were significant except for lymph node control. Among patients who had Stage II disease, those with T1-T2N1 NPC appeared to have a worse outcome compared with patients who had T2N0 NPC. No significant differences in survival rates were found with respect to lymph node size or status for patients with T1-T2N1 disease., Conclusions: When patients with NPC had their disease staged according to the AJCC 1997 classification system, patients with Stage I disease had an excellent outcome after they were treated with radiotherapy alone. Patients with Stage II disease, especially those with T1-T2N1 disease, had a relatively worse outcome, and more aggressive therapy, such as combined-modality treatment, may be indicated for those patients., (Copyright 2003 American Cancer Society.DOI 10.1002/cncr.11485)

To evaluate the efficacy and toxicity of capecitabine as a salvage chemotherapy regimen in Chinese patients with recurrent or metastatic nasopharyngeal carcinoma (NPC) previously treated with platinum-based chemotherapy, 17 patients with recurrent or metastatic NPC previously treated with platinum-based chemotherapy as adjuvant or palliative treatments received oral capecitabine at a dose of 1.25 G/m(2) twice daily in 3-week cycles consisting of 2 weeks of treatment followed by rest period of 1 week. Seven patients had local recurrence, seven had distant metastases, one had loco-regional recurrence, and two had both local/regional recurrence and distant metastases. Patients received a median number of three cycles of capecitabine (range: 1-6). The median follow-up was 7.5 months (range: 3-25.3). All patients were included in the efficacy and adverse events analysis. Three patients (17.6%) achieved partial response and one patient (5.9%) achieved complete response, with an overall response rate of 23.5% (95% confidence interval, 7-50%). The duration of response's were 4.2, 5, 6+, and 23.1+ months. Nine patients (52.9%) had stable disease whereas four (23.5%) had progressive disease. The median time to progression was 4.9 months. The median survival was 7.6 months. Five patients are still alive with an estimated 1-year survival rate of 35%. Treatment-related adverse events were generally mild except hand-foot syndrome which occurred in 58.8% of patients. Capecitabine is an effective salvage regimen in patients with recurrent and metastatic NPC. Capecitabine as a single agent or in combination with other chemotherapeutic agents or treatment modalities should be further studied in NPC., (Copyright 2003 Elsevier Science Ltd.)

Purpose: To evaluate the toxicity and efficacy of concomitant chemoirradiation (CRT) followed by adjuvant chemotherapy compared with radiotherapy (RT) alone in Chinese patients with locoregionally advanced nasopharyngeal carcinoma (NPC)., Methods and Materials: Between March 1997 and September 2000, 47 Chinese patients with Stage III (n = 9, 19%) and IV (n = 38, 81%) NPC were treated with by CRT using cisplatin 100 mg/m(2) on Days 1, 22, and 43 of RT, plus adjuvant chemotherapy using cisplatin 80 mg/m(2) for 1 day and 5-fluorouracil 1 g/m(2) for 4 days on Days 71, 99, and 127. These patients were then compared with a cohort of 47 patients treated between 1990 and 1993 with RT alone, who were matched with respect to T stage, N stage, nodal bilaterality, nodal level, and nodal size. The RT techniques were similar in the two groups but different dose and fractionation schemes were used. The median biologic equivalent dose to 2 Gy per fraction delivered to the nasopharynx was 68 Gy in the CRT group and 65.3 Gy in the RT-alone group., Results: The compliance rates were 62% for concomitant chemotherapy and 40% for adjuvant chemotherapy. No treatment-related deaths occurred. At the end of treatment, 96% of the CRT group and 79% of the RT-alone group achieved a complete response (p = 0.013). With a median follow-up of 26 months, the 3-year relapse-free survival, disease-specific survival, overall survival, local relapse-free survival, nodal relapse-free survival, and distant metastasis-free survival rate for the CRT group and the RT-alone group was 62% vs. 44% (p = 0.048), 67% vs. 71% (p = 0.88), 65% vs. 69% (p = 0.93), 87% vs. 75% (p = 0.059), 95% vs. 80% (p = 0.026), and 75% vs. 70% (p = 0.84), respectively., Conclusion: Our experience indicates that concomitant CRT improves locoregional control in Chinese patients with locoregionally advanced NPC, but our analyses failed to detect any impact on distant failure and survival. The failure to reduce distant metastasis and improve survival may have related in part to the more advanced disease stage in our patients and the relatively low compliance rate of adjuvant chemotherapy. Our findings suggest caution should be exercised in extrapolating the findings of the Intergroup Study 0099 to Chinese patients, and confirmatory results from prospective randomized studies in the endemic population are needed.

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., (Copyright 2001 American Cancer Society.)

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.

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.

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.

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.

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.

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.

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.

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).

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.

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.

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.

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.

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 (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.

A good coverage by the Hong Kong Cancer Registry of cases of the common cancers diagnosed in Hong Kong during 1974-78 is indicated by an excess of cases over deaths registered, which is according to expectation from survival prospects. The trends during 1961-79 showed a rapid increase in mortality from lung cancer in both sexes, a moderate rise in liver cancer in males, and small increases in esophageal cancer in males and colon cancer in females. Cervical cancer was the only neoplasm that showed a decreasing trend, although this was small in proportion. Some epidemiological observations on cancer arising in the lung, liver, larynx, and nasopharynx are presented.

This is a preliminary report of 102 patients with clinical diagnosis of late temporal lobe necrosis after radical radiation therapy for nasopharyngeal carcinoma during 1964 to 1983. Histologic verification was available in 12 cases. All but three patients had been treated in our institute using schedules with doses larger than the conventional 200 cGy per fraction. The incidence rate was 1.03%. In our 80 patients with only one course of external irradiation, the doses to the temporal lobes ranged from 1665 to 2127 ret, or 1286 to 1778 brain tolerance unit (btu). The latent interval ranged from 9 months to 16 years. The median observation period is 33 months. The symptomatology, working diagnosis, treatment, and outcome are described. Surgery was hazardous because of the bilaterality of the involvement and exploration for mere verification of diagnosis was unjustified in typical cases. Treatment with corticosteroid achieved durable objective response in 25 (35%) of 72 patients. The importance of early detection and corticosteroid treatment is discussed.

In patients with nasopharyngeal carcinoma, deafness sometimes occurs following radiotherapy. It is usually conductive, but may be sensorineural. Tinnitus is present frequently and usually is distressing. The role of ventilation tubes (grommets) in relieving these problems was assessed in a prospective randomized controlled trial of 115 patients. In the group with grommets, there was an improvement in hearing, with a reduction of the averaged air-bone gap (p less than .01). This was not found in the control group without ventilation tubes, who developed a larger conductive loss (p less than .01) and, in addition, a slight deterioration of the averaged bone conduction threshold (p less than .01). Surprisingly, the group with grommets did not develop this sensorineural loss (p less than .01). In addition, tinnitus was improved significantly by the insertion of ventilation tubes (p less than .01). Neither necrosis nor stenosis of the external auditory meatus was found in either group.