Ductal carcinoma in situ of breast: detection and treatment pattern in Hong Kong.

INTRODUCTION: The treatment of ductal carcinoma in situ has been widely reported in the western and other Asian countries, but the relevant data in Hong Kong are relatively limited. This study aimed to evaluate the latest detection and treatment pattern for ductal carcinoma in situ in Hong Kong so as to guide planning of future service provision. METHODS: This was a retrospective case series study. A total of 573 patients who registered with the Hong Kong Breast Cancer Registry, and were diagnosed and treated in Hong Kong from January 2001 to December 2011 were reviewed. RESULTS: Compared with invasive breast cancer patients, patients with ductal carcinoma in situ were younger (median, 48.6 vs 50.3 years; P<0.001), had a higher education level (P<0.001), had a higher total monthly family income (P<0.001), and more common breast-screening habits (P<0.001). Significantly more patients with ductal carcinoma in situ underwent breast-conserving surgery than their invasive cancer counterparts (55.8% vs 36.7%; P<0.001). The percentage of screen-detected ductal carcinoma in situ was relatively lower than that reported in other studies, but was still much higher than that in invasive breast cancer patients (29.0% vs 4.7%; P<0.001). Screen-detected patients with ductal carcinoma in situ tended to choose a private hospital instead of a public hospital for treatment (P=0.05) and to undergo breast-conserving surgery (P=0.02). With a median follow-up of 3 years, the crude local recurrence rate after mastectomy and breast-conserving surgery was 0.4% and 3.3%, respectively; 44% of recurrent tumours had developed invasive components. No regional recurrence, distant recurrence, or cancer-related deaths were recorded. CONCLUSIONS: In the absence of a population-based breast screening programme in Hong Kong, ductal carcinoma in situ is more frequently found in the higher social classes and managed in the private sector. The clinical outcome of ductal carcinoma in situ is excellent and more than half of the patients can be successfully managed with breast-conserving surgery.

The evolution of psychological distress trajectories in women diagnosed with advanced breast cancer: a longitudinal study.

BACKGROUND: Anxiety and depression (distress) over the first year following the initial adjuvant therapy for advanced breast cancer (ABC) remain poorly documented in non-Caucasian populations. This study describes trajectories of distress and their determinants in Chinese women with ABC. METHODS: Of the 228 Chinese women newly diagnosed with ABC recruited from six oncology units, 192 completed an interview before their first course of chemotherapy (baseline) and follow-up interviews at 1.5, 3, 6, and 12 months thereafter. At baseline, participants were assessed for supportive care needs, psychological distress, physical symptom distress, optimism, and cancer-related rumination. At follow-up, participants completed the measure of psychological distress. Latent growth mixture modeling was used to identify trajectory patterns of distress. Multinominal logistic regression was used to identify predictors of trajectory patterns adjusted for demographic and medical characteristics. RESULTS: Four distinct trajectories of anxiety and depression were identified. Most women showed low-stable levels of anxiety (68%) and depression (68%), but one in 11 women were chronically anxious (9%) and depressed (9%). Optimism, negative cancer-related rumination, and physical symptom distress predicted both anxiety and depression trajectories. Psychological needs predicted anxiety trajectories. Women in the low-stable distress group reported high optimism, low psychological supportive care needs, low physical symptom distress, and low negative cancer-related rumination. CONCLUSION: Most women with ABC did not experience psychological distress over 12 months following diagnosis of ABC. Preventive interventions should focus on women at risk of high persistent distress and reducing rumination, providing emotional support, and managing physical symptoms.

The strength/weakness of the AJCC/UICC staging system (7th edition) for nasopharyngeal cancer and suggestions for future improvement.

BACKGROUND AND PURPOSE: To evaluate the current AJCC/UICC staging system (7th edition) for nasopharyngeal carcinoma and to explore for future improvement. MATERIALS AND METHODS: A total of 985 patients, initially staged with preceding 5-6th edition, were retrospectively re-staged with the 7th edition. All were assessed by magnetic resonance imaging, and all 945 non-disseminated patients were irradiated with conformal/intensity-modulated technique. RESULTS: Staging factors by both the 5-6th edition and the 7th edition were strongly significance for important endpoints (p<0.001). Down-staging of the previous T2a to T1 and, stages IIA to I in the 7th edition was appropriate. However, the impacts on overall stage distribution and prognostication were minimal. Further down-staging of the current T2 to T1, N2 to N1, stages II to I, and merging of N3a and N3b, stages IVA and IVB were suggested. With the 7th edition, the 5-year disease-specific survival (DSS) was 100% for stage I, 95% for II, 90% for III, 67% for IVA, 68% for IVB and 18% for IVC. The corresponding DSS for the proposed stages I, II, III and IV were 95%, 86%, 67% and 18%, respectively. CONCLUSIONS: The changes introduced in the 7th edition were appropriate, but the magnitude of improvement was minimal. With improving results by modern management, further simplification of the staging system is suggested. The proposed system could lead to more accurate prognostication, further validation is warranted.

A phase II study of pemetrexed combined with cisplatin in patients with recurrent or metastatic nanopharyngeal carcinoma.

Pemetrexed is a novel chemotherapy agent with good efficacy and toxicity profiles. This phase II study aimed at evaluating its use in combination with cisplatin for recurrent or metastatic nasopharyngeal carcinoma (NPC). All participating patients had metastatic or recurrent NPC with prior treatment by platinum-based chemotherapy. The study regimen comprised of pemetrexed 500 mg/m(2) and cisplatin 75 mg/m(2), repeated 3-weekly for 4 cycles. Efficacy evaluation was based on both radiological and biochemical responses. Patients with no progressive disease and good tolerance were given another 2-4 cycles. Fifteen patients were treated for a total of 4-8 cycles (median, 6 cycles); 9 had distant metastases and 6 had loco-regional recurrences only. Reduction of DNA copies of EB virus by ≥50% was observed in 93% accessible patients, with 21% of them being biochemical complete response (CR). Radiologically, 1 (7%) patient achieved CR, 2 (13%) achieved partial response and 8 (53%) had stable diseases. The median time to progression was 30 weeks. Treatment was well tolerated with only 1 (7%) patient developing grade 4 toxicity (of anemia). The most common grade 3 toxicities were neutropenia (27%) and anemia (20%). The baseline mean total QOL scores (as measured with FACT-H&N version 4) was 100.4 and showed no significant change after the fourth cycle (95.6, p=0.20) and sixth cycle (91.9, p=0.15). Pemetrexed in combination with cisplatin is a well tolerated regimen with encouraging efficacy for metastatic and recurrent NPC. Further evaluation of its role in the management of NPC is warranted.

Validation of the Chinese version of the short-form Supportive Care Needs Survey Questionnaire (SCNS-SF34-C).

BACKGROUND: There is no instrument available in Chinese for assessing psychosocial needs. This study aimed to assess the validity and reliability of the Chinese version of the Supportive Care Needs Survey short form (SCNS-SF34-C) in Chinese women with breast cancer (BC). METHODS: The Chinese version of the 34-item SCNS-SF34-C, a self-report measure for assessing psychosocial unmet needs, was administered to 348 Chinese women with BC at the outpatient oncology unit. Exploratory factor analysis (EFA) tested the factor structure. The internal consistency, convergent, divergent, and discriminant validity of the identified factor structure were assessed. RESULTS: In contrast to the five-factor structure identified in the original 34-item SCNS-SF34, our EFA produced a 33-item solution accounting for 54% of score variance comprising four-factors: (1) Health system, information, and patient support, (2) Psychological needs, (3) Physical and daily living, and (4) Sexuality needs. Separate dimensions for Health system and information, and the Patient care and support domains were not supported. Cronbach alphas ranged from 0.75 to 0.92. Correlations of psychological and physical symptom distress measures indicated acceptable convergent validity. No correlation with optimism and positive affect measures indicated divergent validity. Discriminant validity was demonstrated by effective differentiation between clinically distinct patient groups (no active treatment versus active treatment; advanced BC versus localized BC). DISCUSSION: The Chinese version of the Supportive Care Needs Survey has suitable factor structure and psychometric properties for use in assessing psychosocial needs among Chinese women with BC. Further validation is needed for other cancer types.

Replication study of SNP associations for colorectal cancer in Hong Kong Chinese.

BACKGROUND: Recent genome-wide association studies of colorectal cancer (CRC) have identified common single-nucleotide polymorphisms (SNPs) mapping to 10 independent loci that confer modest increased risk. These studies have been conducted in European populations and it is unclear whether these observations generalise to populations with different ethnicities and rates of CRC. METHODS: An association study was performed on 892 CRC cases and 890 controls recruited from the Hong Kong Chinese population, genotyping 32 SNPs, which were either associated with CRC in previous studies or are in close proximity to previously reported risk SNPs. RESULTS: Twelve of the SNPs showed evidence of an association. The strongest associations were provided by rs10795668 on 10p14, rs4779584 on 15q14 and rs12953717 on 18q21.2. There was significant linear association between CRC risk and the number of independent risk variants possessed by an individual (P=2.29 × 10(-5)). CONCLUSION: These results indicate that some previously reported SNP associations also impact on CRC risk in the Chinese population. Possible reasons for failure of replication for some loci include inadequate study power, differences in allele frequency, linkage disequilibrium structure or effect size between populations. Our results suggest that many associations for CRC are likely to generalise across populations.

Relationships between explanatory style, posttraumatic growth and posttraumatic stress disorder symptoms among Chinese breast cancer patients.

Many existing models posit that cognitive processing style is an important factor affecting self-perceived positive changes. In this study, the effects of explanatory style (the manner in which people cognitively process and explain why they experience good and bad events) on both posttraumatic growth (PTG) and posttraumatic stress disorder (PTSD) symptoms were examined among 90 Chinese women with breast cancer. It was found that explanatory style for good events, but not for bad events, was significantly associated with self-reported PTG. Women who attributed the causes of positive events to internal, global and stable factors tended to report more posttraumatic growth. In contrast, explanatory style for bad events, as opposed to good events, was significantly and positively correlated with PTSD symptoms. Among the three dimensions of explanatory style (internal, stable and global), the tendency to globalise the causes of good and bad events were the most important predictors of self-reported PTG and PTSD symptoms, respectively. While enhancing an optimistic explanatory style for bad events might reduce posttraumatic stress symptoms, cultivating an optimistic explanatory style for good events is likely to increase self-perceived positive changes after breast cancer diagnosis and treatment.

Delayed presentation of symptomatic breast cancers in Hong Kong: experience in a public cancer centre.

OBJECTIVE: Delayed presentation is an important obstacle to improving cancer treatment outcomes. We aimed to study the magnitude of this problem in Hong Kong and the factors associated with delayed presentation of patients with symptomatic breast cancers. DESIGN: Retrospective study using self-administered questionnaires. SETTING: Clinical Oncology Department in a regional public hospital in Hong Kong. PATIENTS: A total of 158 Chinese women with breast cancer referred to our hospital between October 2006 and December 2007 consented to participate in this study. Among these, 59 (37%) patients were referred after having surgery in private sector. RESULTS: The mean total delay (from first symptom to treatment) was 22 weeks. The mean patient delay (from first symptom to first consultation) was 13 weeks, constituting the largest component (60%) of the total delay. After symptom onset, the delay exceeded 12 weeks for consulting a doctor in 29%, and for receipt of treatment in 52% of them. Low family income (

Randomized trial of radiotherapy plus concurrent-adjuvant chemotherapy vs radiotherapy alone for regionally advanced nasopharyngeal carcinoma.

BACKGROUND: Current practice of adding concurrent-adjuvant chemotherapy to radiotherapy (CRT) for treating advanced nasopharyngeal carcinoma is based on the Intergroup-0099 Study published in 1998. However, the outcome for the radiotherapy-alone (RT) group in that trial was substantially poorer than those in other trials, and there were no data on late toxicities. Verification of the long-term therapeutic index of this regimen is needed. METHODS: Patients with nonkeratinizing nasopharyngeal carcinoma staged T1-4N2-3M0 were randomly assigned to RT (176 patients) or to CRT (172 patients) using cisplatin (100 mg/m(2)) every 3 weeks for three cycles in concurrence with radiotherapy, followed by cisplatin (80 mg/m(2)) plus fluorouracil (1000 mg per m(2) per day for 4 days) every 4 weeks for three cycles. Primary endpoints included overall failure-free rate (FFR) (the time to first failure at any site) and progression-free survival. Secondary endpoints included overall survival, locoregional FFR, distant FFR, and acute and late toxicity rates. All statistical tests were two-sided. RESULTS: The two treatment groups were well balanced in all patient characteristics, tumor factors, and radiotherapy parameters. Adding chemotherapy statistically significantly improved the 5-year FFR (CRT vs RT: 67% vs 55%; P = .014) and 5-year progression-free survival (CRT vs RT: 62% vs 53%; P = .035). Cumulative incidence of acute toxicity increased with chemotherapy by 30% (CRT vs RT: 83% vs 53%; P < .001), but the 5-year late toxicity rate did not increase statistically significantly (CRT vs RT: 30% vs 24%; P = .30). Deaths because of disease progression were reduced statistically significantly by 14% (CRT vs RT: 38% vs 24%; P = .008), but 5-year overall survival was similar (CRT vs RT: 68% vs 64%; P = .22; hazard ratio of CRT = 0.81, 95% confidence interval = 0.58 to 1.13) because deaths due to toxicity or incidental causes increased by 7% (CRT vs RT: 1.7% vs 0, and 8.1% vs 3.4%, respectively; P = .015). CONCLUSIONS: Adding concurrent-adjuvant chemotherapy statistically significantly reduced failure and cancer-specific deaths when compared with radiotherapy alone. Although there was no statistically significant increase in major late toxicity, increase in noncancer deaths narrowed the resultant gain in overall survival.

Should young age be a contra-indication to breast conservation treatment in Chinese women? Twelve-year experience from a public cancer centre in Hong Kong.

OBJECTIVE: It has been proposed that young women should not be treated by breast conservation treatment because of a higher risk of local recurrences and worse survival. We therefore examined whether breast conservation treatment in young Chinese women yielded inferior clinical outcomes compared to modified radical mastectomy. DESIGN: Retrospective study. SETTING: Clinical oncology department in a public hospital in Hong Kong. PATIENTS: A total of 258 Chinese women with invasive breast cancer, aged below 40 years, and referred between January 1994 and July 2006. RESULTS: A total of 124 (48%) and 134 (52%) patients were treated by breast conservation treatment and modified radical mastectomy, respectively. Mastectomy patients tended to have larger primary tumours (P<0.001) and more nodal involvement (P<0.001). At a median follow-up of 6.5 years, there was no significant difference in the local failure-free survival rate (92% vs 93%, P=0.324) and loco-regional failure-free survival rate (89% vs 88%, P=0.721) in patients having breast conservation treatment and mastectomy. Probably due to their earlier presentation with disease, the former actually had better 6-year distant failure-free survival (88% vs 71%, P=0.002) and overall survival (92% vs 81%, P=0.173) rates. Multivariate analyses showed that both the resection margin status (hazard ratio=2.77, P=0.050) and the presence of peritumoural vascular invasion (hazard ratio=3.01, P=0.038) were independent predictors of local recurrence; the nodal status (hazard ratio=3.91, P<0.001) was the only predictive factor for overall survival. The choice of breast conservation treatment (vs modified radical mastectomy) had no apparent adverse impact on all the clinical outcome parameters analysed. CONCLUSION: Breast conservation treatment is a reasonable option for many suitably selected young Chinese women.

Major late toxicities after conformal radiotherapy for nasopharyngeal carcinoma-patient- and treatment-related risk factors.

PURPOSE: To retrospectively analyze the factors affecting late toxicity for nasopharyngeal carcinoma. METHODS AND MATERIALS: Between 1998 and 2003, 422 patients were treated with a conformal technique with 2-Gy daily fractions to a total dose of 70 Gy. Conventional fractionation (5 fractions weekly) was used in 232 patients and accelerated fractionation (6 fractions weekly) in 190 patients. One hundred seventy-one patients were treated with the basic radiotherapy course alone (Group 1), 55 patients had an additional boost of 5 Gy in 2 fractions (Group 2), and 196 patients underwent concurrent cisplatin-based chemotherapy (Group 3). RESULTS: The 5-year overall toxicity rate was significantly greater in Group 3 than in Group 1 (37% vs. 27%, p = 0.009). Although the overall rate in Group 2 was not elevated (28% vs. 27%, p = 0.697), a significant increase in temporal lobe necrosis was observed (4.8% vs. 0%, p = 0.015). Multivariate analyses showed that age and concurrent chemotherapy were significant factors. The hazard ratio of overall toxicity attributed to chemotherapy was 1.99 (95% confidence interval, 1.32-2.99, p = 0.001). The mean radiation dose to the cochlea was another significant factor affecting deafness, with a hazard ratio of 1.03 (95% confidence interval, 1.01-1.05, p = 0.005) per 1-Gy increase. The cochlea that received >50 Gy had a significantly greater deaf rate (Group 1, 18% vs. 7%; and Group 3, 22% vs. 14%). CONCLUSION: The therapeutic margin for nasopharyngeal carcinoma is extremely narrow, and a significant increase in brain necrosis could result from dose escalation. The significant factors affecting the risk of deafness included age, concurrent chemoradiotherapy, and greater radiation dose to the cochlea.

Sensorineural hearing loss after treatment of nasopharyngeal carcinoma: a longitudinal analysis.

PURPOSE: To analyze the effects of radiotherapy (RT) and chemotherapy in relation to sensorineural hearing loss (SNHL) after contemporary treatment of nasopharyngeal carcinoma. METHODS AND MATERIALS: A total of 87 nasopharyngeal carcinoma patients were treated with RT or chemoradiotherapy using either three-dimensional conformal RT or intensity-modulated RT between 2004 and 2005. Tympanometry and pure-tone audiogram assessments were performed before treatment and then serially at 6-month intervals. The dose-volume data of the cochlea were analyzed. The effects of cisplatin administered in concurrent and nonconcurrent phases was explored. RESULTS: Of the 170 eligible ears, RT (n = 30) and chemoradiotherapy (n = 140) resulted in 40% (n = 12) and 56.4% (n = 79) persistent SNHL (> or = 15 dB loss), respectively, after a median follow-up of 2 years. SNHL at a high frequency was more frequent statistically in the chemoradiotherapy group than in the RT-alone group (55% vs. 33.3%, p < 0.01), but not at a low frequency (7.9% vs. 16.7%, p = 0.14). Within the chemoradiotherapy group, the mean cochlea dose and concurrent cisplatin dose were important determinants of high-frequency SNHL, with an odds ratio of 1.07/Gy increase (p = 0.01) and an odds ratio of 1.008/mg/m(2) increase (p < 0.01), respectively. Age, gender, and nonconcurrent cisplatin dose were not statistically significant factors. A mean radiation dose to the cochlea of <47 Gy would result in <15% of patients developing severe (> or = 30 dB) high-frequency SNHL. CONCLUSION: The results of our study have shown that high-frequency SNHL is significantly related to the mean cochlea dose and the concurrent cisplatin dose. A mean dose constraint of 47 Gy to the cochlea is recommended to minimize SNHL after chemoradiotherapy.

HER2 overexpression of breast cancers in Hong Kong: prevalence and concordance between immunohistochemistry and in-situ hybridisation assays.

OBJECTIVES: To evaluate the prevalence of human epidermal growth factor receptor 2 (HER2) gene overexpression in breast cancer patients encountered in Hong Kong and the concordance of HER2 findings from primary immunohistochemistry assays and confirmatory in-situ hybridisation assays. DESIGN: Retrospective study. SETTING: Department of Clinical Oncology in a public hospital in Hong Kong. PATIENTS: All patient referrals between July 2006 and June 2007 with newly diagnosed invasive breast cancer (for prevalence evaluation), and all patients treated at our unit with confirmatory in-situ hybridisation tests performed within the study period (for concordance evaluation). RESULTS: There were 272 consecutive breast cancer patients eligible for prevalence evaluation. The distribution for immunohistochemistry staining in 249 cases for scores 0, 1+, 2+, and 3+ were 99 (40%), 40 (16%), 58 (23%), and 52 (21%) respectively. In the remaining 23 patients, four and 19 breast cancers were unscored and reported by immunohistochemistry to be HER2-positive and -negative, respectively. The overall HER2 overexpression rate (3+ or reported as positive) was 21%. HER2 overexpression was associated with grade 3 histology (P<0.001) and negative hormonal receptor status (P<0.001). However, it was not associated with age (P=0.525), T-classification (P=0.740), N-classification (P=0.691), nor group stages (P=0.433). Of the 37 patients with confirmatory in-situ hybridisation tests performed, 10 (71%) of 14 with immunohistochemistry staining of 3+ and 1 (4%) of 23 with immunohistochemistry staining of 2+ were found to have HER2 gene amplification. CONCLUSIONS: More than 25% of HER2 overexpression identified by immunohistochemistry assays in this Hong Kong cohort could not be verified by confirmatory in-situ hybridisation assays. Compliance with the latest guidelines for HER2 testing should improve the future accuracy and concordance.

Surveillance mammography after breast conservation therapy in Hong Kong: effectiveness and feasibility of risk-adapted approach.

Annual surveillance mammography is commonly recommended after breast conservation therapy (BCT). We retrospectively reviewed its effectiveness on 511 invasive and non-invasive breast cancers treated with BCT between 1994 and 2003. The median follow-up was 5.9 years. The 5-year actuarial ipsilateral breast tumour recurrence (IBTR) rate was 4.5% and contralateral breast cancer (CBC) rate was 2.0% (representing eight times increase in risk). IBTR of 43% and 62% CBC were first detected by surveillance mammography. The IBTR detection rates per 1000 mammograms were 5.2 for patients (n=349) with one or more IBTR risk factors (age 45, positive/close margins or histological grade 3) and 0.6 for patients (n=162) without. No survival difference was observed between different modes of IBTR detection (p=0.342). In conclusion, a risk-adapted approach of limiting ipsilateral surveillance to patients with IBTR risk is possible but its implementation will be complicated by the continued need of contralateral surveillance.

Evaluation of the prognostic value of 2005 St Gallen risk categories for operated breast cancers in Hong Kong.

Incorporating various new and conventional risk factors, the 2005 St Gallen risk categorization is a potentially useful prognostic tool for breast cancers. We conducted a retrospective study to evaluate its application in Hong Kong. Of the 902 included female breast cancers with median follow-up of 5.4 years, 7%, 63% and 30% patients were classified as low-, intermediate- and high-risk categories, respectively. Their corresponding 5-year distant disease-free survivals (DDFS) were 100%, 92% and 72%, respectively (p<0.00005). In the intermediate-risk category, node-positive patients had marginally inferior 5-year DDFS than node-negative patients (89% vs. 93%, p=0.0551). In the high-risk category, patients having HER2 overexpressed tumors and 1-3 positive nodes had significantly better DDFS than other patients with > or = 4 positive nodes (89% vs. 65%, p=0.0001). Overall, the 2005 St Gallen risk categorization had high prognostic value. However, the impact of HER2 overexpression might be affected by reproducibility of HER2 tests.

Treatment of Stage IV(A-B) nasopharyngeal carcinoma by induction-concurrent chemoradiotherapy and accelerated fractionation: impact of chemotherapy schemes.

PURPOSE: The aim of this study was to evaluate the impact of different chemotherapy regimens in patients with advanced nasopharyngeal carcinoma (NPC) treated by induction-concurrent chemoradiotherapy. METHODS AND MATERIALS: Between 1998 and 2003, 75 Stage IV(A-B) NPC patients were treated with 3 cycles of induction chemotherapy with cisplatin plus 5-fluorouracil (PF) (n = 41) or cisplatin plus gemcitabine (PG) (n = 34), followed by accelerated radiotherapy in concurrence with 2 cycles of cisplatin. In 18 (24%) patients, cisplatin was completely replaced by carboplatin in both concurrent cycles, mainly because of borderline renal functions. RESULTS: The median follow-up was 3.6 years. The 3-year locoregional failure-free survival, progression-free survival, and overall survival of the whole group were 80%, 68%, and 80% respectively. No significant difference was found between patients treated with either induction regimens. However, patients with only carboplatin in the 2 concurrent cycles had significantly inferior 3-year locoregional failure-free survival (56% vs. 86%, p = 0.014), progression-free survival (39% vs. 72%, p = 0.001), and overall survival (61% vs. 87%, p = 0.046) when compared with the rest of the group. In multivariate analysis, the complete replacement of cisplatin by carboplatin during concurrent chemoradiotherapy was still an independent adverse factor in locoregional failure-free survival (hazard ratio, 3.662; 95% CI, 1.145-11.765; p = 0.029) and progression-free survival (hazard ratio, 3.390; 95% CI, 1.443-7.937; p = 0.005). CONCLUSIONS: The more convenient PG regimen is as effective as the PF regimen as induction chemotherapy for patients with advanced NPC. Replacing cisplatin with carboplatin in the concurrent phase carries a poor prognosis.

Wide local excision and radiotherapy for the treatment of ductal carcinoma in situ of the breast: the Hong Kong experience.

AIMS: Breast conservation treatment for ductal carcinoma in situ (DCIS) was unpopular in the Chinese population and the outcome was seldom reported. We conducted a single-centre retrospective study to examine the clinical outcome of women in Hong Kong. MATERIALS AND METHODS: Seventy-five Chinese women were treated with wide local excision and radiotherapy for DCIS of the breast between 1994 and 2003. Only 26 (34.7%) women had non-palpable DCIS detected by screening mammograms. All women were treated with whole breast irradiation of 50 Gy in 2 Gy daily fractions, with 50 (66.7%) women receiving an additional electron boost of 10-16 Gy. RESULTS: The median follow-up was 5.1 years (range 2.0-10.7). At the last assessment, four women developed local recurrences, but all remained disease-free after salvage mastectomy. The 5-year actuarial local failure-free rate and cause-specific survival rate were 92.9% (95% confidence interval 89.4-96.4) and 100.0%, respectively. Cosmetic results were rated as good to excellent in all women. On univariate analysis of prognostic factors for local failure, only a close (< or = 2 mm) final resection margin approached statistical significance (hazard ratio 9.108; 95% confidence interval 0.946-87.655; P = 0.056). The 5-year actuarial local failure-free rates for women with a close (< or = 2 mm) final resection margin and women with wider margins were 77.0 and 98.2%, respectively. CONCLUSIONS: Despite geographical and demographic differences, the clinical outcome after wide local excision and radiotherapy for DCIS of the breast in Chinese women is comparable with that in Western series. Efforts are needed to achieve cosmetically acceptable tumour-free margins greater than 2 mm.

Treatment of stage IV(A-B) nasopharyngeal carcinoma by induction-concurrent chemoradiotherapy and accelerated fractionation.

PURPOSE: To explore a more effective strategy for treating nasopharyngeal carcinoma with extensive locoregional disease. METHODS AND MATERIALS: Between October 1998 and January 2003, 49 patients with Stage IV(A-B) disease infiltrating or abutting neurologic structures were treated with induction-concurrent chemotherapy and accelerated radiotherapy (RT). A combination of cisplatin and 5-fluorouracil was used in the induction phase and single-agent cisplatin in the concurrent phase. All patients were irradiated with conformal techniques at 2 Gy/fraction, six daily fractions weekly, to a total dose of 70 Gy. RESULTS: Although 92% of patients had one or more acute toxicities Grade 3 or worse, 96% completed the whole course of RT, and 92% had five or more cycles of chemotherapy. The great majority of toxicities were uneventful, but 1 patient died of neutropenic sepsis. With a median follow-up of 3.1 years, 20 patients had failure at one or more sites and 15 patients died. The 3-year locoregional and distant failure-free rate was 77% and 75%, respectively, and the overall survival rate was 71%. At last follow-up, 27% of patients had developed late Grade 3 or worse toxicity (24% were hearing impairments), but none had radiation-induced neurologic damage. CONCLUSION: The current strategy achieved encouraging results for this poor prognostic group, and confirmation of the therapeutic gain by a prospective randomized trial is warranted.

Preliminary results of a randomized study on therapeutic gain by concurrent chemotherapy for regionally-advanced nasopharyngeal carcinoma: NPC-9901 Trial by the Hong Kong Nasopharyngeal Cancer Study Group.

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.

Survival outcome of patients with nasopharyngeal carcinoma with first local failure: a study by the Hong Kong Nasopharyngeal Carcinoma Study Group.

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.