Current management of pregnancy-associated breast cancer.

Pregnancy-associated breast cancer is the most common malignancy during pregnancy with an expected rise in incidence. The belief in the need for termination of pregnancy and that chemotherapy is contra-indicated during pregnancy is challenged by recent evidence. Patients can consider breast-conserving surgery and sentinel lymph node biopsy with acceptably low fetal risk from radiation exposure. A range of chemotherapeutics is possible in the second trimester in terms of drug class and frequency. Hormonal therapy and monoclonal antibody therapy are contra-indicated during pregnancy and lactation. Fetal outcome after in-utero exposure to chemotherapy appears similar to that in a non-pregnant population. Future pregnancy, in most situations, does not appear to be contra-indicated but a multidisciplinary and patient-centred approach is recommended. Fertility preservation techniques are also being developed with reported success and consequent pregnancies.

Comparison of clinical and pathological characteristics between screen-detected and self-detected breast cancers: a Hong Kong study.

INTRODUCTION: Breast cancer is the leading cause of death of Hong Kong women with increasing incidence. This study aimed to determine any prognostic differences between screen-detected and self-detected cases of breast cancer in a cohort of Hong Kong patients. METHODS: This was a case series with internal comparison carried out in a private hospital in Hong Kong. Approximately 3000 cases of Chinese patients diagnosed with ductal carcinoma in situ or invasive breast cancer were reviewed. RESULTS: The screen-detected group showed better pathological characteristics than the self-detected group. Number of lymph nodes involved, invasive tumour size, and tumour grade were more favourable in the screen-detected group. There was also a lower proportion of patients with pure invasive ductal carcinoma and mastectomy in the screen-detected group. CONCLUSION: This study provides indirect evidence that women in the local population may gain clinical benefit from regular breast cancer screening. The findings need to be validated in a representative population of Hong Kong women.

The Mononuclear Phagocyte System in Organ Transplantation.

The mononuclear phagocyte system (MPS) comprises monocytes, macrophages and dendritic cells (DCs). Over the past few decades, classification of the cells of the MPS has generated considerable controversy. Recent studies into the origin, developmental requirements and function of MPS cells are beginning to solve this problem in an objective manner. Using high-resolution genetic analyses and fate-mapping studies, three main mononuclear phagocyte lineages have been defined, namely, macrophage populations established during embryogenesis, monocyte-derived cells that develop during adult life and DCs. These subsets and their diverse subsets have specialized functions that are largely conserved between species, justifying the introduction of a new, universal scheme of nomenclature and providing the framework for therapeutic manipulation of immune responses in the clinic. In this review, we have commented on the implications of this novel MPS classification in solid organ transplantation.

Initial experience with the Oncotype DX assay in decision-making for adjuvant therapy of early oestrogen receptor-positive breast cancer in Hong Kong.

OBJECTIVE: To examine the impact of the 21-gene Oncotype DX Breast Cancer Assay on the adjuvant treatment decision-making process for early-stage breast cancer in Hong Kong. DESIGN: Retrospective study. SETTING: Private hospital, Hong Kong. PATIENTS: Study included cases of early-stage breast cancer (T1-2N0-1M0, oestrogen receptor-positive, human epidermal growth factor receptor 2-negative) that were presented at a multidisciplinary breast meeting at a single site. Cases were selected for Oncotype DX testing with the assistance of Adjuvant! Online. The recommendations for adjuvant therapy before and after obtaining the Oncotype DX Recurrence Score results were analysed. RESULTS: A total of 154 cases that met the inclusion criteria were discussed at our multidisciplinary breast meeting. Of these, 64 cases with no clear recommendation by the Meeting Panel were selected for this study and reviewed. The distribution of Recurrence Score results was similar to that reported by others, with a somewhat higher proportion of low Recurrence Scores. Treatment recommendation was changed for 20 (31%) patients after the Oncotype DX result was received. Of the changes in treatment decisions, 16 (80%) were changes to lower-intensity regimens (either equipoise or hormonal therapy). The number of cases receiving an equipoise recommendation decreased by nine (82%), based on the additional information provided by the Oncotype DX test. CONCLUSION: The Oncotype DX Recurrence Score information impacts the decision-making process for adjuvant therapy for early-stage breast cancer in the multidisciplinary care setting in Hong Kong. A larger-scale study is required to gain more experience, evaluate its impact more thoroughly, and assess its cost-effectiveness.

Early data from the first population-wide breast cancer-specific registry in Hong Kong.

BACKGROUND: Current measures for breast cancer prevention and options for treatment adopted in Hong Kong are mainly based on research data and clinical evidence from overseas. It is essential to establish a cancer-specific registry to monitor the status of breast cancer in Hong Kong. OBJECTIVES: We summarized the current status of breast cancer in Hong Kong based on the data collected from Hong Kong Breast Cancer Registry (HKBCR). METHODS: Prevalent and newly diagnosed breast cancers (including in situ and invasive breast cancers) were registered in the HKBCR. Information on patient demographics, risk factors, medical information, and survival were analyzed and reported in this study. RESULTS: Data of 2,330 breast cancer patients were analyzed. We observed an earlier median age at diagnosis in Hong Kong than those reported in other countries. Distribution of cancer stage was: stage 0 (11.4%), stage I (31.4%), stage II (41%), stage III (12.5%), stage IV (0.8%), and unclassified (2.9%). The percentages of patients who received surgery, chemotherapy, radiation therapy, and endocrine therapy were 98.7, 67.9, 64.8, and 64.1%, respectively. At a median follow-up of 1.2 years, locoregional recurrence was recorded at 2%, distant recurrence at 2.8%, and breast-cancer-related mortality at 0.3%. CONCLUSIONS: The HKBCR serves as a surveillance program to monitor disease and treatment patterns. It is pivotal to support research for more effective breast cancer prevention and treatment strategies in Hong Kong.

A randomized study of aprepitant, ondansetron and dexamethasone for chemotherapy-induced nausea and vomiting in Chinese breast cancer patients receiving moderately emetogenic chemotherapy.

OBJECTIVES: This is a single center, randomized, double-blind placebo-controlled study to evaluate the NK(1)-receptor antagonist, aprepitant, in Chinese breast cancer patients. The primary objective was to compare the efficacy of aprepitant-based antiemetic regimen and standard antiemetic regimen for the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients who received moderately emetogenic chemotherapy. The secondary objective was to compare the patient-reported quality of life in these two groups of patients. PATIENTS AND METHODS: Eligible breast cancer patients were chemotherapy-naive and treated with adjuvant AC chemotherapy (i.e. doxorubicin 60 mg/m(2) and cyclophosphamide 600 mg/m(2)). Patients were randomly assigned to either an aprepitant-based regimen (day 1, aprepitant 125 mg, ondansetron 8 mg, and dexamethasone 12 mg before chemotherapy and ondansetron 8 mg 8 h later; days 2 through 3, aprepitant 80 qd) or a control arm which consisted of standard regimen (day 1, ondansetron 8 mg and dexamethasone 20 mg before chemotherapy and ondansetron 8 mg 8 h later; days 2 through 3, ondansetron 8 mg bid). Data on nausea, vomiting, and use of rescue medication were collected with a self-report diary, patients quality of life were assessed by self-administered Functional Living Index-Emesis (FLIE). RESULTS: Of 127 patients randomized, 124 were assessable. For CINV in Cycle 1 AC, there was no significant difference in the proportion of patients with reported complete response, complete protection, total control, 'no vomiting', 'no significant nausea' and 'no nausea'. The requirement of rescue medication appears to be lesser in patients treated with the aprepitant-based regimen compared to those with the standard regimen (11% vs. 20%; P = 0.06). Assessment of FLIE revealed that while there was no difference in the nausea domain and the total score between the two groups; however, patients receiving standard antiemetic regimen had significantly worse quality of life in the vomiting domain (mean score [SD] = 23.99 [30.79]) when compared with those who received the aprepitant-based regimen (mean score [SD] = 3.40 [13.18]) (P = 0.0002). Both treatments were generally well tolerated. Patients treated with the aprepitant-based regimen had a significantly lower incidence of neutropenia (53.2% vs. 35.5%, P = 0.0468), grade >or= 3 neutropenia (21.0% vs. 45.2, P = 0.0042) and delay in subsequent cycle of chemotherapy (8.1% vs. 27.4%, P = 0.0048). CONCLUSION: The aprepitant regimen appears to reduce the requirement of rescue medication when compared with the control regimen for prevention of CINV in patients receiving both an anthracycline and cyclophosphamide, and is associated with a better quality of life during adjuvant AC chemotherapy.

A split-organ delineation approach for dose optimisation for intensity-modulated radiotherapy for advanced T-stage nasopharyngeal carcinoma.

AIMS: To assess the dosimetric effect of using a split-organ delineation approach during intensity-modulated radiotherapy (IMRT) treatment planning for advanced T-stage nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: Twenty NPC patients with T3-4 tumours were studied. A reference (REF) IMRT plan was generated based on a standard treatment planning protocol, with a set of user-defined dose constraints for optimisation. An investigative (INV) IMRT plan was then generated based on the same protocol, but treating several organs at risk (OARs; parotid glands, temporal lobes, cochlea, auditory nerves and planning organ at risk volume [PRV] of the brainstem) as split organs consisting of target-overlapping and non-target-overlapping sub-segments. These sub-segments were assigned independent dose constraints. The REF and INV plans were compared with respect to target coverage and OAR sparing. Target coverage was evaluated by the Dmin (minimum dose), V66/V60 (percentage volume of gross target volume [GTV]/planning target volume [PTV] receiving 66 Gy/60 Gy), target conformity index (CI), and tumour control probability (TCP). The sparing of OARs was evaluated by the commonly used dose end points for the respective OAR, and normal tissue complication probability (NTCP). RESULTS: For PTV coverage, the INV plan was superior to the REF plan in terms of Dmin (P=0.000), CI (P=0.005) and TCP (P=0.002). This is attributed to an increase in dose to the PTV-OAR overlapping sub-segments. Regarding the sparing of OARs, there was a significant reduction in the mean dose of the parotid glands (P=0.002), and a slight, but non-significant, increase in NTCP of the temporal lobes, cochlea and brainstem. CONCLUSIONS: Using a split-organ delineation approach in IMRT treatment planning for advanced T-stage NPC, a significant improvement in the target coverage and TCP could be achieved, whereas the mean dose of the parotid was reduced significantly. There was insignificant change in the NTCP of the temporal lobe, parotid gland, cochlea and brainstem, but a significant change in the NTCP of the auditory nerve. The approach provides the planner extra room to manipulate the dose constraints during optimisation, and to obtain the desired result in less attempts. This approach also has the potential to be used in a broader context for IMRT planning for other tumour sites.

A randomised controlled trial of prophylactic levonorgestrel intrauterine system in tamoxifen-treated women.

OBJECTIVE: To study the prophylactic use of levonorgestrel intrauterine system (LNG-IUS) in the prevention of endometrial pathology in women having breast cancer treated with tamoxifen. DESIGN: Randomised controlled trial. SETTING: A tertiary teaching hospital. POPULATION: One hundred and thirteen women (66 premenopausal/47 postmenopausal) who required adjuvant tamoxifen for breast cancer after the completion of postoperative radiotherapy and chemotherapy. METHODS: Women were randomised to treatment group (prophylactic LNG-IUS insertion before the commencement of tamoxifen) or control group. Uterine cavity was examined by outpatient hysteroscopy and endometrial biopsy before and at 12 months after commencement of tamoxifen. MAIN OUTCOME MEASURES: De novo endometrial pathology at 1 year of tamoxifen. RESULTS: Women in the treatment group had a much lower incidence of endometrial polyp (1.8 versus 15.5%, P= 0.017) (relative risk: 0.12; 95% CI: 0.02-0.91) at 12 months. There was no significant difference in the incidence of submucosal fibroid between the two groups (1.8 versus 3.4%, P= 1.0). LNG-IUS was retained in 95% women in the treatment group at 1 year. CONCLUSION: LNG-IUS reduces the occurrence of de novo endometrial polyp in women treated with tamoxifen for breast cancer.

Feasibility of using interpolated contours of targets and organs at risk in intensity-modulated radiation therapy treatment planning for advanced-stage nasopharyngeal carcinoma.

To assess the dosimetric effect of using interpolated contours in planning intensity-modulated radiation therapy (IMRT) for advanced T-stage nasopharyngeal carcinoma. The present study focused on T3-T4 tumours where the proximity of targets to neurological organs poses a stringent test on the feasibility of such an approach. Contours of targets and organs were delineated on CT images of 2.5-mm interval and a reference IMRT plan was generated. An investigative (INV) IMRT plan was then generated with the same planning protocol, but based on interpolated contours that replaced deleted contours on alternate slices. The reference and INV plans were compared. Regarding target coverage, all targets in the INV plans met the acceptance criteria except for the PTV in one case. Regarding organs, the mean dose to 1% volume of the brainstem and spinal cord in the INV plans were kept below their dose limits. No significant differences in the mean doses to others organs were found. Satisfactory target coverage and protection of critical organs to a degree similar to full-scale contouring could be achieved with use of interpolated contours. The saving in manpower time for contouring is expected to significantly improve the throughput of the IMRT planning process.

Adjuvant chemoradiation for gastric cancer: experience in the Chinese population.

AIMS: The role of adjuvant chemoradiation for gastric cancer after curative R0 gastrectomy was first established by the US Intergroup 0116 study. Although confirmatory studies are in progress, few data are available regarding its application to the Chinese population. We describe our radiotherapy technique and report the treatment results in Hong Kong. MATERIALS AND METHODS: This was a single centre retrospective study on 63 Chinese patients who underwent adjuvant chemoradiation for gastric adenocarcinoma between June 2000 and December 2004. The treatment protocol was based on that of the Intergroup study. Computed tomography planned anteroposterior opposing field arrangement and treatment under breath hold at deep inspiration position were adopted. RESULTS: In total, 63 patients, mean age 50 years, with gastric cancer stage IB to limited metastatic IV disease were analysed. The median follow-up time was 27.2 months. The relapse-free survival and overall survival at 3 years were 50 and 54%, respectively. The recurrence pattern was dominated by distant failure and only one patient developed isolated locoregional recurrence. Of the 10 patients who had positive microscopic surgical margins after surgery, seven had recurred and died. On multivariate analysis, margin status was the only significant prognosticator for survival. Thirty per cent of patients experienced grade 3 or above acute toxicity (24% haematological, 14% gastrointestinal) and one patient died of neutropenic sepsis. There was one case of grade 3 late toxicity. CONCLUSIONS: The outcome after adjuvant chemoradiation for gastric cancer seemed to be favourable, with manageable toxicities, in the Chinese population. Locoregional failure was uncommon. Patients with microscopic surgical margin involvement had a very high failure rate despite adjuvant chemoradiation.

Overall survival after concurrent cisplatin-radiotherapy compared with radiotherapy alone in locoregionally advanced nasopharyngeal carcinoma.

This phase III randomized study compared concurrent cisplatin-radiotherapy (CRT) versus radiotherapy (RT) alone in patients with locoregionally advanced nasopharyngeal carcinoma. A total of 350 patients were randomly assigned to receive external RT alone or concurrently with cisplatin at a dosage of 40 mg/m(2) weekly. The primary endpoint was overall survival, and the median follow-up was 5.5 years. The 5-year overall survival was 58.6% (95% confidence interval [CI] = 50.9% to 66.2%) for the RT arm and 70.3% (95% CI = 63.4% to 77.3%) for the CRT arm. In Cox regression analysis adjusted for T stage, age, and overall stage, the difference in overall survival was statistically significantly in favor of concurrent CRT (P = .049, hazard ratio [HR] = 0.71 [95% CI = 0.5 to 1.0]). Subgroup analysis demonstrated that there was no difference between overall survival in the arms for T1/T2 stage (P = .74, HR = 0.93 [95% CI = 0.59 to 1.4]), whereas there was a difference between the arms for T3/T4 stage (P = .013, HR = 0.51 [95% CI = 0.3 to 0.88]), favoring the CRT arm. The regimen of weekly concurrent CRT is a promising standard treatment strategy for locoregionally advanced nasopharyngeal carcinoma patients.

Treatment of nasopharyngeal carcinoma with intensity-modulated radiotherapy: the Hong Kong experience.

PURPOSE: To evaluate the efficacy of using intensity-modulated radiotherapy (IMRT) in the primary treatment of nasopharyngeal carcinoma (NPC), including the role of dose escalation above 66 Gy level. METHODS AND MATERIALS: Between July 2000 and September 2002, 63 newly diagnosed NPC patients were treated with IMRT. The disease was Stage I in 9 (14%), Stage II in 18 (29%), Stage III in 22 (35%), and Stage IV in 14 (22%). The prescribed dose was 66 Gy to the gross tumor volume (GTV) and positive neck nodes, 60 Gy to the planning target volume (PTV), and 54-60 Gy to the clinically negative neck. All 20 (100%) patients with T1-2a tumors received intracavitary brachytherapy (ICB) boost, and 15/42 (36%) patients with T2b-T4 tumors received conformal boost (8 Gy/4 fractions). Nineteen patients with advanced stage disease also received either neoadjuvant or concurrent chemotherapy. Acute and late normal tissue effects were graded according to the Radiation Therapy Oncology Group (RTOG) radiation morbidity scoring criteria. Local relapse-free survival (LRFS), nodal relapse-free survival (NRFS), distant metastasis-free survival (DMFS), and overall survival (OS) were estimated using the Kaplan-Meier method. RESULTS: With a median follow-up of 29 months (range 8-45 months), 4 patients developed local in-field failure, 1 patient developed regional relapse, and 13 patients developed distant metastases. All 4 patients with local failure had either T3 or T4 disease before primary treatment and did not have ICB or conformal boost. The 3-year actuarial LRFS, NRFS, DMFS, and OS were 92%, 98%, 79%, and 90%, respectively. Multivariate analysis showed that dose escalation above 66 Gy was significantly associated with better PFS and DMFS, whereas GTV size was a significant adverse factor for OS. The worst acute mucositis was Grade 1 or 2 in 36 (59%), and Grade 3 in 25 (41%) patients. Acute dysphagia requiring tube feeding occurred in 5 (8%) patients. The proportion of patients with Grade 2-3 xerostomia was 57% at 3 months, and 23% at 2 years after IMRT. Within the subset of patients with a mean parotid dose of <31 Gy, the proportions with Grade 2-3 xerostomia were 30% and 17% at 3 months and 2 years, respectively. CONCLUSION: Our experience of using IMRT in the primary treatment of NPC showed a very high rate of locoregional control and favorable toxicity profile. Furthermore, we found that dose escalation above 66 Gy of IMRT-based therapy was a significant determinant of progression-free survival and distant metastasis-free survival for advanced T-stage tumors. Distant metastases represent the predominant mode of treatment failure.

Phase II study of neoadjuvant carboplatin and paclitaxel followed by radiotherapy and concurrent cisplatin in patients with locoregionally advanced nasopharyngeal carcinoma: therapeutic monitoring with plasma Epstein-Barr virus DNA.

PURPOSE: To assess the efficacy of neoadjuvant paclitaxel and carboplatin (TC) followed by concurrent cisplatin and radiotherapy (RT) in patients with locoregionally advanced nasopharyngeal carcinoma (NPC) and to monitor treatment response with plasma Epstein-Barr virus (EBV) DNA. PATIENTS AND METHODS: Thirty-one patients with International Union Against Cancer stages III and IV undifferentiated NPC had two cycles of paclitaxel (70 mg/m2 on days 1, 8, and 15) and carboplatin (area under the curve 6 mg/mL/min on day 1) on a 3-weekly cycle, followed by 6 to 8 weeks of cisplatin (40 mg/m2 weekly) and RT at 66 Gy in 2-Gy fractions. Plasma EBV DNA was measured serially using the real-time quantitative polymerase chain reaction method. Results All patients completed planned treatment. Response to neoadjuvant TC was as follows: 12 patients (39%) achieved partial response (PR) and 18 achieved (58%) complete response (CR) in regional nodes; five patients (16%) achieved PR and no patients achieved CR in nasopharynx. At 6 weeks after RT, one patient (3%) achieved PR and 30 patients (97%) achieved CR in regional nodes, and 31 patients (100%) achieved CR in nasopharynx; 29 patients (93%) had EBV DNA level of less than 500 copies/mL. Neoadjuvant TC was well tolerated, and the most common acute toxicity of cisplatin plus RT was grade 3 mucositis (55%). At median follow-up of 33.7 months (range, 7 to 39.3 months), six distant and three locoregional failures occurred. Plasma EBV DNA level increased significantly in eight of nine patients who experienced treatment failure but did not increase in those who did not. The 2-year overall and progression-free survival rates were 91.8% and 78.5%, respectively. CONCLUSION This strategy was feasible and resulted in excellent local tumor control. Serial plasma EBV DNA provides a noninvasive method of monitoring response in NPC.

Psychosocial impact of breast cancer surgeries in Chinese patients and their spouses.

BACKGROUND AND PURPOSE: This pilot study assesses the psychosocial impact of different modalities of breast cancer surgery in Chinese patients and their husbands. METHODS: Thirty-six patients who underwent conservative breast therapy (BCT) for breast cancer were compared with 36 women who underwent total mastectomy (TM) on four aspects of psychosocial adjustment. They were matched in pairs in terms of stage of disease, age and time since surgery. Where available, their husbands were also consented for similar assessment. RESULTS: Women who underwent BCT showed a significantly better response to their body and sexual image than those who underwent TM. This difference did not translate into any significant difference in terms of emotional and symptomatic aspects, daily activities, or fear of recurrences. The husbands of patients in the TM group showed significantly more emotional and symptomatic distress and greater change in the perception of their wives' body and sexual images. CONCLUSION: This is the first of such study conducted in a Chinese population. The lack of differences in certain psychosocial aspects may indicate a generally good adjustment in the TM patients after their surgery. It may also relate to the fact that volunteers for the study were themselves representative only of the patient population who adapted well to the surgery, and those patients who were emotionally distressed tended to decline to participate. Psychosocial disruption in the patients' families is reflected in our study where patients' husbands in the TM group were significantly more disturbed. However, due to the limited number of patients studied, the findings are not yet conclusive and require further studies for confirmation.

Concurrent chemotherapy-radiotherapy compared with radiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: progression-free survival analysis of a phase III randomized trial.

PURPOSE: Nasopharyngeal carcinoma (NPC) is highly sensitive to both radiotherapy (RT) and chemotherapy. This randomized phase III trial compared concurrent cisplatin-RT (CRT) with RT alone in patients with locoregionally advanced NPC. PATIENTS AND METHODS: Patients with Ho's N2 or N3 stage or N1 stage with nodal size > or = 4 cm were randomized to receive cisplatin 40 mg/m(2) weekly up to 8 weeks concurrently with radical RT (CRT) or RT alone. The primary end point was progression-free survival (PFS). RESULTS: Three hundred fifty eligible patients were randomized. Baseline patient characteristics were comparable in both arms. There were significantly more toxicities, including mucositis, myelosuppression, and weight loss in the CRT arm. There were no treatment-related deaths in the CRT arm, and one patient died during treatment in the RT-alone arm. At a median follow-up of 2.71 years, the 2-year PFS was 76% in the CRT arm and 69% in the RT-alone arm (P =.10) with a hazards ratio of 1.367 (95% confidence interval [CI], 0.93 to 2.00). The treatment effect had a significant covariate interaction with tumor stage, and a subgroup analysis demonstrated a highly significant difference in favor of the CRT arm in Ho's stage T3 (P =.0075) with a hazards ratio of 2.328 (95% CI, 1.26 to 4.28). For T3 stage, the time to first distant failure was statistically significantly different in favor of the CRT arm (P =.016). CONCLUSION: Concurrent CRT is well tolerated in patients with advanced NPC in endemic areas. Although PFS was not significantly different between the concurrent CRT arm and the RT-alone arm in the overall comparison, PFS was significantly prolonged in patients with advanced tumor and node stages.

Final report of a randomized trial on altered-fractionated radiotherapy in nasopharyngeal carcinoma prematurely terminated by significant increase in neurologic complications.

PURPOSE: The aim of the present study was to compare the survival, local control and complications of conventional/accelerated-hyperfractionated radiotherapy and conventional radiotherapy in nonmetastatic nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: From February 1993 to October 1995, 159 patients with newly diagnosed nonmetastatic (M0) NPC with N0 or 4 cm or less N1 disease (Ho's N-stage classification, 1978) were randomized to receive either conventional radiotherapy (Arm I, n = 82) or conventional/accelerated-hyperfractionated radiotherapy (Arm II, n = 77). Stratification was according to the T stage. The biologic effective dose (10 Grays) to the primary and the upper cervical lymphatics were 75.0 and 73.1 for Arm I and 84.4 and 77.2 for Arm II, respectively. RESULTS: With comparable distribution among the T stages between the two arms, the free from local failure rate at 5 years after radiotherapy was not significantly different between the two arms (85.3%; 95% confidence interval, 77.2-93.4% for Arm I; and 88.9%; 95% confidence interval, 81.7-96.2% for Arm II). The two arms were also comparable in overall survival, relapse-free survival, and rates of distant metastasis and regional relapse. Conventional/accelerated-hyperfractionated radiotherapy was associated with significantly increased radiation-induced damage to the central nervous system (including temporal lobe, cranial nerves, optic nerve/chiasma, and brainstem/spinal cord) in Arm II. Although insignificant, radiation-induced cranial nerve(s) palsy (typically involving VIII-XII), trismus, neck soft tissue fibrosis, and hypopituiturism and hypothyroidism occurred more often in Arm II. In addition, the complications occurred at significantly shorter intervals after radiotherapy in Arm II. CONCLUSION: Accelerated hyperfractionation when used in conjunction with a two-dimensional radiotherapy planning technique, in this case the Ho's technique, resulted in increased radiation damage to the central nervous system without significant improvement in efficacy.

Clinical outcomes of post-operative locoregional radiotherapy in pre-menopausal and post-menopausal Chinese women with breast cancer.

BACKGROUND AND PURPOSES: Recent randomized studies from the West show that post-operative locoregional radiotherapy improves survival in lymph node (LN) positive pre-menopausal women with breast cancer but this benefit has not been established in the Chinese population. There is no published study on clinical outcomes (locoregional recurrence, survival and toxicities) of post-operative locoregional radiotherapy in Chinese women with breast cancer. MATERIALS AND METHODS: We conducted a retrospective study of 399 female Chinese patients with breast cancer who had received post-mastectomy locoregional radiotherapy in our center between 1984 and 1990. The patients were stratified according to tumor size, menopausal and LN status. We analyzed the incidence and pattern of locoregional recurrence, distant recurrence, survival rates and toxicity related to radiotherapy. RESULTS: Of the 399 patients 216 were pre-menopausal and 183 were post-menopausal. The mean age was 49.3 years (23-83). Distribution of tumor size and LN status of the two groups was similar. Median follow-up was 71.9 months. Locoregional recurrence occurred in 57 (14.3%) patients (pre-menopausal 24 (11.1%); post-menopausal 33 (18.3%) P=0.489). Recurrence was more common in LN positive patients (18.2%) than LN negative patients (9.2%). The pattern of locoregional recurrence was: chest wall 24, axilla LN 12, supraclavicular LN 10, chest plus LN 11. The distant recurrence rate was 39.6% for all patients and 75.4% for patients with locoregional recurrences. The overall 10-year survival rate for all patients was 54%. For LN positive patients the 10-year survival rate of pre-menopausal and post-menopausal women was 38 and 51%, respectively (P=0.207), and for LN negative patients the rate was 73 and 70%, respectively (P=0.603). Acute skin toxicity included redness (30.8%), dry desquamation (12.8%), and wet desquamation (6. 8%). Long-term toxicities included skin atrophy (0.3%), telangectasia (3.3%), pneumonitis (2.8%) and brachial plexus palsy (1.3%). CONCLUSIONS: In our series Chinese patients with node-positive breast cancer have a relatively high locoregional recurrence rate in spite of mastectomy and post-operative radiotherapy. Limited use of adjuvant system chemotherapy may account, at least in part, for this finding. Clinical outcomes of post-operative radiotherapy in pre-menopausal and post-menopausal breast cancer patients are similar.

Primary orbital Ewing's sarcoma: report of a case and review of the literature.

Primary orbital Ewing's sarcoma is a very rare condition. Since the first case was reported in 1950, only 7 other cases have been reported in the English literature. Herein we describe the ninth, the only bilateral and the youngest case of primary orbital Ewing's sarcoma occurring in a 2-year-old boy, who presented to us with bilateral painless proptosis. Tissue biopsy of the tumour was obtained through the nasal sinus. Immunohistological studies of the biopsy tissue confirmed the diagnosis of Ewing's sarcoma. No distant site of the tumour was found so this was considered a primary orbital tumour. Combined chemotherapy and radiotherapy without surgical resection achieved an encouraging result in that the patient has remained in remission for 30 months after completion of treatment. The successful use of combined chemotherapy and radiotherapy, without surgery, adds further support to evidence that surgical excision may be avoided in selected cases of primary orbital Ewing's sarcoma.

Multimodality treatment of primary lymphoepithelioma-like carcinoma of the lung.

BACKGROUND: Lymphoepithelioma-like carcinoma (LELC) of the lung occurs at a higher frequency in Asian compared with Western patients. Its association with Epstein-Barr virus varies among different ethnic groups. METHODS: Nine patients with primary LELC of the lung treated at a single institution with a multimodality approach comprised of surgery, chemotherapy, and radiotherapy are reported. Chemotherapy was comprised of cisplatin, 100 mg/m2, on Day 1 and 5-fluorouracil, 1 g/m2, on Days 2, 3, and 4. RESULTS: Five male and 4 female patients were treated over a 3-year period. Eight patients were non-smokers. Three patients had operable disease. Two of these patients received adjuvant radiotherapy or chemotherapy and remained free of recurrence at 18 and 20 months, respectively; 1 patient received no adjuvant treatment, and palliative chemotherapy was given for subsequent recurrent disease. Six patients had inoperable disease and received palliative chemotherapy +/- radiotherapy. Five patients had distant metastatic disease at presentation. Of the 7 patients who were evaluable for response to chemotherapy, 71.4% had a partial response and 28.6% had progressive disease. One patient who was evaluable for response to radiotherapy achieved a partial response. CONCLUSIONS: Primary LELC of the lung has a high rate of systemic metastasis and is highly chemosensitive. A multimodality approach to the management of this disease is recommended.

Isolated testicular relapse after bone marrow transplant with total body irradiation and testicular boost in acute lymphoblastic leukemia.

A 7-year-old boy with Ph+ ALL received an allogeneic BMT in second remission. Conditioning included cyclophosphamide 60 mg/kg for 2 days, TBI 2 Gy twice daily for 3 days (12 Gy) and a single testicular boost of 4 Gy. He remained in hematological remission after BMT but developed isolated testicular relapse at 17 months. He underwent orchiectomy of the affected testis, 24 Gy testicular radiotherapy and systemic chemotherapy. He remains in remission 24 months after the testicular relapse. This is the first report of isolated testicular relapse which received a testicular irradiation boost included in the conditioning.