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In the KATHERINE study (NCT01772472), patients with HER2-positive early breast cancer (EBC) and residual invasive disease after neoadjuvant chemotherapy plus HER2-targeted therapy who were treated with adjuvant trastuzumab emtansine (T-DM1) had a 50% reduction in the risk of an invasive disease-free survival (IDFS) event compared to patients treated with adjuvant trastuzumab. In metastatic disease, T-DM1 has resulted in higher rates of thrombocytopenia in Asian versus non-Asian patients. Here, we report safety and efficacy in Chinese patients from KATHERINE. Patients with HER2-positive EBC and residual invasive disease after taxane- and trastuzumab-containing neoadjuvant chemotherapy followed by surgery were randomized 1:1 to 14 cycles of adjuvant T-DM1 or trastuzumab. The primary endpoint was time to an IDFS event. Among Chinese patients (T-DM1 n = 51, trastuzumab n = 50), T-DM1 treatment resulted in a 43% reduction in risk of an IDFS event compared to trastuzumab (HR = 0.57; 95% CI 0.25–1.31), with similar results for secondary endpoints. As in the global population, Chinese patients receiving T-DM1 versus trastuzumab had more grade ≥ 3 adverse events (AEs; 39.2% versus 4.1%) and AEs leading to treatment discontinuation (27.5% versus 0%). The most common grade ≥ 3 AE with T-DM1 was thrombocytopenia (21.6%), a frequency higher than the frequency in the global population (5.7%). Grade ≥ 3 hemorrhage was reported in 1 patient (T-DM1 arm). In the KATHERINE study, T-DM1 demonstrated increased efficacy compared to trastuzumab in Chinese patients. Consistent with previous data in Asian patients, T-DM1 was associated with more grade ≥ 3 AEs, and AEs leading to discontinuation, which was driven by an increase in thrombocytopenia.

Purpose BioPATH is a non-interventional study evaluating the relationship of molecular biomarkers (PTEN deletion/downregulation, PIK3CA mutation, truncated HER2 receptor [p95HER2], and tumor HER2 mRNA levels) to treatment responses in Asian patients with HER2+ advanced breast cancer treated with lapatinib and other HER2-targeted agents. Materials and methods Female Asian HER2+ breast cancer patients (n=154) who were candidates for lapatinib-based treatment following metastasis and having an available primary tumor biopsy specimen were included. The primary endpoint was progression-free survival (PFS). Secondary endpoints were response rate, overall survival on lapatinib, correlation between biomarker status and PFS for any previous trastuzumab-based treatment, and conversion/conservation rates of the biomarker status between tissue samples collected at primary diagnosis and at recurrence/metastasis. Potential relationships between tumor mRNA levels of HER2 and response to lapatinib-based therapy were also explored. Results p95HER2, PTEN deletion/downregulation, and PIK3CA mutation did not demonstrate any significant co-occurrence pattern and were not predictive of clinical outcomes on either lapatinib-based treatment or any previous trastuzumab-based therapy in the metastatic setting. Proportions of tumors positive for p95HER2 expression, PIK3CA mutation, and PTEN deletion/down-regulation at primary diagnosis were 32%, 31.2%, and 56.2%, respectively. Despite limited availability of paired samples, biomarker status patterns were conserved in most samples. HER2 mRNA levels were not predictive of PFS on lapatinib. Conclusion The prevalence of p95HER2 expression, PIK3CA mutation, and PTEN deletion/downregulation at primary diagnosis were similar to previous reports. Importantly, no difference was observed in clinical outcome based on the status of these biomarkers, consistent with reports from other studies.

Purpose: Neratinib, an irreversible pan-HER tyrosine kinase inhibitor, has demonstrated systemic efficacy and intracranial activity in various stages of HER2+ breast cancer. NALA was a phase III randomized trial that assessed the efficacy and safety of neratinib + capecitabine (N+C) against lapatinib + capecitabine (L+C) in HER2+ metastatic breast cancer (mBC) patients who had received ≥2 HER2-directed regimens. Descriptive analysis results of the Asian subgroup in the NALA study are reported herein.Methods: 621 centrally-assessed HER2+ mBC patients were enrolled, 202 of whom were Asian. Those with stable, asymptomatic brain metastases (BM) were eligible for study entry. Patients were randomized 1:1 to N (240mg qd) + C (750mg/m2 bid, day 1-14) with loperamide prophylaxis, or to L (1250mg qd) + C (1000mg/m2 bid, day 1-14) in 21-day cycles. Co-primary endpoints were centrally-assessed progression free survival (PFS) and overall survival (OS). Secondary endpoints included time to intervention for central nervous system (CNS) disease, objective response rate, duration of response (DoR), clinical benefit rate, and safety.Results: 104 and 98 Asian patients were randomly assigned to receive N+C or L+C, respectively. Median PFS of N+C and L+C was 7.0 and 5.4 months (P=0.0014), respectively. Overall cumulative incidence of intervention for CNS disease was lower with N+C (27.9 versus 33.8%; P=0.039). Both median OS (23.8 versus 18.7 months; P=0.185) and DoR (11.1 versus 4.2 months; PConclusion: Consistent with the efficacy profile observed in the overall study population, Asian patients with HER2+ mBC, who had received ≥2 HER2-directed regimens, may also benefit from N+C. No new safety signals were noted. Clinical Trial Registration: NCT01808573

Purpose Neratinib, an irreversible pan-HER tyrosine kinase inhibitor, has demonstrated systemic efficacy and intracranial activity in various stages of HER2+breast cancer. NALA was a phase III randomized trial that assessed the efficacy and safety of neratinib+capecitabine (N+C) against lapatinib+capecitabine (L+C) in HER2+ metastatic breast cancer (mBC) patients who had received ≥ 2 HER2-directed regimens. Descriptive analysis results of the Asian subgroup in the NALA study are reported herein. Methods 621 centrally assessed HER2+ mBC patients were enrolled, 202 of whom were Asian. Those with stable, asymptomatic brain metastases (BM) were eligible for study entry. Patients were randomized 1:1 to N (240 mg qd) + C (750 mg/m2 bid, day 1–14) with loperamide prophylaxis or to L (1250 mg qd) + C (1000 mg/m2 bid, day 1–14) in 21-day cycles. Co-primary endpoints were centrally assessed progression-free survival (PFS) and overall survival (OS). Secondary endpoints included time to intervention for central nervous system (CNS) disease, objective response rate, duration of response (DoR), clinical benefit rate, and safety. Results 104 and 98 Asian patients were randomly assigned to receive N+C or L+C, respectively. Median PFS of N+C and L+C was 7.0 and 5.4 months (P = 0.0011), respectively. Overall cumulative incidence of intervention for CNS disease was lower with N+C (27.9 versus 33.8%; P = 0.039). Both median OS (23.8 versus 18.7 months; P = 0.185) and DoR (11.1 versus 4.2 months; P Conclusion Consistent with the efficacy profile observed in the overall study population, Asian patients with HER2+ mBC, who had received ≥ 2 HER2-directed regimens, may also benefit from N+C. No new safety signals were noted. Clinical trial registration NCT01808573

Multiple myeloma is a relatively uncommon plasma cell malignancy. Preclinical and clinical studies have suggested that aspirin might modify the risk of multiple myeloma. We performed a systematic review and meta-analysis of studies to examine the association between regular aspirin use and risk of multiple myeloma. Five observational studies including 332,660 adults were evaluated. The pooled estimate had a hazard ratio of 0.90 (95% confidence interval =0.58−1.39; P=0.638). Odds ratios from the two case-control studies were similar. The findings demonstrated that there was no significant association between aspirin use and the risk of multiple myeloma., Highlights • This is a systematic review of aspirin use on the incidence risk of multiple myeloma. • There is no evidence that aspirin modifies the risk of multiple myeloma. • More studies are needed to assess the impact of aspirin on the risk of multiple myeloma.

Objectives Previous studies reported that prognostic nutritional index (PNI), a marker of host inflammatory and nutritional status, is associated with prognoses in a number of cancer types. Thus, we investigated PNI at diagnosis as a prognostic factor in FL. Methods We reviewed FL patients in Tuen Mun Hospital, Hong Kong from 2000 to 2014 (n=88). PNI was calculated by serum albumin (g/L)+5×absolute lymphocyte count (10/L). We determined the best PNI cut-off value using receiver-operating characteristic curves. The extent to which progression-free survival (PFS) and overall survival differed by PNI cut-off was assessed using Kaplan-Meier and log-rank tests. Cox proportional hazards model was utilized to adjust for covariates. Results The best cut-off value for PNI was determined to be 45. Patients with high PNI (>45) had a higher complete response (CR) rate after primary treatment, 46 of 61 (75.4%) patients with high PNI had CR, compared with 10 of 23 (43.5%) for low PNI (2-sample test of proportions P-value=0.006). Further, higher PNI at relapse as a continuous variable was associated with superior postprogression survival with a hazard ratio (HR) 0.88 (95% confidence interval [CI], 0.81-0.96). In multivariate analysis, high PNI at diagnosis had superior PFS (adjusted HR of 0.37; 95% CI, 0.15-0.93). Conclusions PNI was shown to be independent prognostic factor of PFS in FL. It is a cheap and widely available biomarker. Future study is needed to validate its prognostic value and clinical utility in a prospective cohort.

Introduction The management of human epidermal growth factor receptor 2 (HER2)-positive breast cancer has changed dramatically with the introduction and widespread use of HER2-targeted therapies. There is, however, relatively limited real-world information about the effectiveness and safety of trastuzumab emtansine (T-DM1) in Hong Kong Chinese patients. We assessed the efficacy and toxicity profiles among local patients with HER2-positive advanced breast cancer who had received T-DM1 therapy in the second-line setting and beyond. Methods This retrospective study involved five local centres that provide service for over 80% of the breast cancer population in Hong Kong. The study period was from December 2013 to December 2015. Patients were included if they had recurrent or metastatic histologically confirmed HER2+ breast cancer who had progressed after at least one line of anti-HER2 therapy including trastuzumab. Patients were excluded if they received T-DM1 as first-line treatment for recurrent or metastatic HER2+ breast cancer. Patient charts including biochemical and haematological profiles were reviewed for background information, T-DM1 response, and toxicity data. Adverse events were documented during chemotherapy and 28 days after the last dose of medication. Results Among 37 patients being included in this study, 28 (75.7%) had two or more lines of anti-HER2 agents and 26 (70.3%) had received two or more lines of palliative chemotherapy. Response assessment revealed that three (8.1%) patients had a complete response, eight (21.6%) a partial response, 11 (29.7%) a stable disease, and 12 (32.4%) a progressive disease; three patients could not be assessed. The median duration of response was 17.3 (95% confidence interval, 8.4-24.8) months. The clinical benefit rate (complete response + partial response + stable disease, ≥12 weeks) was 37.8% (95% confidence interval, 22.2%-53.5%). The median progression-free survival was 6.0 (95% confidence interval, 3.3- 9.8) months and the median overall survival had not been reached by the data cut-off date. Grade 3 or 4 toxicities included thrombocytopaenia (13.5%), raised alanine transaminase (8.1%), anaemia (5.4%), and hypokalaemia (2.7%). No patient died as a result of toxicities. Conclusions In patients with HER2-positive advanced breast cancer who have been heavily pretreated with anti-HER2 agents and cytotoxic chemotherapy, T-DM1 is well tolerated and provided a meaningful progression-free survival of 6 months and an overall survival that has not been reached. Further studies to identify appropriate patient subgroups are warranted.

Background The current exploratory analysis was performed to evaluate the efficacy and safety of everolimus for treatment of human epidermal growth factor receptor 2-positive (HER2+) advanced breast cancer in the Asian subset of patients in the BOLERO-1 trial. Methods Postmenopausal women with HER2+ advanced breast cancer, who had not received systemic therapy for advanced disease, were randomized 2:1 to receive everolimus or placebo, plus trastuzumab and paclitaxel. The two primary end points were investigator-assessed progression-free survival (PFS) in the full population and in the hormone receptor-negative (HR–) subpopulation. Secondary end points included assessment of the objective response rate, the clinical benefit rate, and safety. Results In the Asian subset, median PFS was similar in the everolimus (n = 198) and placebo (n = 105) arms in the full analysis set (hazard ratio = 0.82 (95% CI 0.61–1.11)). In the HR– subpopulation, everolimus prolonged median PFS by 10.97 months vs placebo (25.46 vs 14.49 months; hazard ratio = 0.48 (95% CI 0.29–0.79)). In the everolimus arm of the Asian subset, the most common adverse events of any grade were stomatitis (62.2%), diarrhea (48.0%), rash (43.4%) and neutropenia (42.3%). Neutropenia (grade 3: 27.6%; grade 4: 4.6%) and decreased neutrophil count (grade 3: 11.2%; grade 4: 3.6%) were the most frequent grade 3/4 adverse events. Serious adverse events included pneumonia (5.1%), pneumonitis (3.1%), and interstitial lung disease (3.1%). There were three deaths (1.5%) during treatment in the everolimus arm vs none in the placebo arm. Conclusions The efficacy and safety of everolimus plus trastuzumab and paclitaxel as first-line treatment for HER2+ advanced breast cancer in the Asian subset was consistent with that reported previously in the overall population. Trial registration ClinicalTrials.gov, NCT00876395. Registered on 2 April 2009. Electronic supplementary material The online version of this article (doi:10.1186/s13058-017-0839-0) contains supplementary material, which is available to authorized users.

The role of radiotherapy (RT) in improving survival of patients with diffuse large B-cell lymphoma (DLBCL) of the Waldeyer ring (WR) remains controversial. Therefore, this retrospective cohort study aimed to determine the role of RT in the treatment of DLBCL of the WR as well as the effects of associated covariates. Patients (n=35) with stage I to II DLBCL of the WR who underwent treatment at our center between 1994 and 2010 were retrospectively investigated. All patients had histologic diagnosis and staging workup completed. Overall survival (OS), event-free survival (EFS), and disease-free survival (DFS) were analyzed. Variables with a P-value of 1 and age above 60 years were also found to negatively influence OS and EFS. RT was associated with improved OS and EFS in stage I to II DLBCL of the WR. Future prospective studies are required to confirm these findings.

BACKGROUND: ExteNET showed that 1 year of neratinib, an irreversible pan-HER tyrosine kinase inhibitor, significantly improves 2-year invasive disease-free survival after trastuzumab-based adjuvant therapy in women with HER2-positive breast cancer. We report updated efficacy outcomes from a protocol-defined 5-year follow-up sensitivity analysis and long-term toxicity findings. METHODS: In this ongoing randomised, double-blind, placebo-controlled, phase 3 trial, eligible women aged 18 years or older (≥20 years in Japan) with stage 1-3c (modified to stage 2-3c in February, 2010) operable breast cancer, who had completed neoadjuvant and adjuvant chemotherapy plus trastuzumab with no evidence of disease recurrence or metastatic disease at study entry. Patients who were eligible patients were randomly assigned (1:1) via permuted blocks stratified according to hormone receptor status (hormone receptor-positive vs hormone receptor-negative), nodal status (0 vs 1-3 vs or ≥4 positive nodes), and trastuzumab adjuvant regimen (given sequentially vs concurrently with chemotherapy), then implemented centrally via an interactive voice and web-response system, to receive 1 year of oral neratinib 240 mg/day or matching placebo. Treatment was given continuously for 1 year, unless disease recurrence or new breast cancer, intolerable adverse events, or consent withdrawal occurred. Patients, investigators, and trial funder were masked to treatment allocation. The predefined endpoint of the 5-year analysis was invasive disease-free survival, analysed by intention to treat. ExteNET is registered with ClinicalTrials.gov, number NCT00878709, and is closed to new participants. FINDINGS: Between July 9, 2009, and Oct 24, 2011, 2840 eligible women with early HER2-positive breast cancer were recruited from community-based and academic institutions in 40 countries and randomly assigned to receive neratinib (n=1420) or placebo (n=1420). After a median follow-up of 5·2 years (IQR 2·1-5·3), patients in the neratinib group had significantly fewer invasive disease-free survival events than those in the placebo group (116 vs 163 events; stratified hazard ratio 0·73, 95% CI 0·57-0·92, p=0·0083). The 5-year invasive disease-free survival was 90·2% (95% CI 88·3-91·8) in the neratinib group and 87·7% (85·7-89·4) in the placebo group. Without diarrhoea prophylaxis, the most common grade 3-4 adverse events in the neratinib group, compared with the placebo group, were diarrhoea (561 [40%] grade 3 and one [BACKGROUND: ExteNET showed that 1 year of neratinib, an irreversible pan-HER tyrosine kinase inhibitor, significantly improves 2-year invasive disease-free survival after trastuzumab-based adjuvant therapy in women with HER2-positive breast cancer. We report updated efficacy outcomes from a protocol-defined 5-year follow-up sensitivity analysis and long-term toxicity findings.METHODS: In this ongoing randomised, double-blind, placebo-controlled, phase 3 trial, eligible women aged 18 years or older (≥20 years in Japan) with stage 1-3c (modified to stage 2-3c in February, 2010) operable breast cancer, who had completed neoadjuvant and adjuvant chemotherapy plus trastuzumab with no evidence of disease recurrence or metastatic disease at study entry. Patients who were eligible patients were randomly assigned (1:1) via permuted blocks stratified according to hormone receptor status (hormone receptor-positive vs hormone receptor-negative), nodal status (0 vs 1-3 vs or ≥4 positive nodes), and trastuzumab adjuvant regimen (given sequentially vs concurrently with chemotherapy), then implemented centrally via an interactive voice and web-response system, to receive 1 year of oral neratinib 240 mg/day or matching placebo. Treatment was given continuously for 1 year, unless disease recurrence or new breast cancer, intolerable adverse events, or consent withdrawal occurred. Patients, investigators, and trial funder were masked to treatment allocation. The predefined endpoint of the 5-year analysis was invasive disease-free survival, analysed by intention to treat. ExteNET is registered with ClinicalTrials.gov, number NCT00878709, and is closed to new participants.FINDINGS: Between July 9, 2009, and Oct 24, 2011, 2840 eligible women with early HER2-positive breast cancer were recruited from community-based and academic institutions in 40 countries and randomly assigned to receive neratinib (n=1420) or placebo (n=1420). After a median follow-up of 5·2 years (IQR 2·1-5·3), patients in the neratinib group had significantly fewer invasive disease-free survival events than those in the placebo group (116 vs 163 events; stratified hazard ratio 0·73, 95% CI 0·57-0·92, p=0·0083). The 5-year invasive disease-free survival was 90·2% (95% CI 88·3-91·8) in the neratinib group and 87·7% (85·7-89·4) in the placebo group. Without diarrhoea prophylaxis, the most common grade 3-4 adverse events in the neratinib group, compared with the placebo group, were diarrhoea (561 [40%] grade 3 and one [INTERPRETATION: At the 5-year follow-up, 1 year of extended adjuvant therapy with neratinib, administered after chemotherapy and trastuzumab, significantly reduced the proportion of clinically relevant breast cancer relapses-ie, those that might lead to death, such as distant and locoregional relapses outside the preserved breast-without increasing the risk of long-term toxicity. An analysis of overall survival is planned after 248 events.FUNDING: Wyeth, Pfizer, and Puma Biotechnology.

A 25 year old man was referred to the oncology unit with a three week history of a neck lump that was progressively increasing in size, and atypical lymphoid cells on fine needle aspiration cytology. The patient also reported mild exertional dyspnoea and drenching night sweats, but no weight loss, occupational exposure to harmful substances, recent travel, or high risk sexual behaviour. He had smoked cigarettes since he was 16. On examination, the right supraclavicular lymph node was palpable and measured 3 cm in diameter. Chest radiography showed a widened mediastinum but no lung lesions. Contrast enhanced computed tomography of the thorax was performed (fig 1). Core biopsy of the node showed partial effacement of nodal architecture by scattered large cells in a background of reactive lymphocytes, eosinophils, and plasma cells with some collagen fibrosis. These large cells stained positive for CD15 and CD30 and negative for CD45. Figure 2 shows an example micrograph from biopsy (not from the patient described). Fig 1 Axial contrast enhanced computed tomography of the thorax showing an anterior mediastinal mass, with a central hypodense area suggestive of necrosis (red arrow) Fig 2 Micrograph showing a Reed-Sternberg cell and normal lymphocytes. Reed-Sternberg cells are often binucleated with prominent nucleoli, having an …

Aims: The docetaxel and cyclophosphamide (TC) regimen is increasingly popular as adjuvant chemotherapy for operable breast cancers. We conducted a retrospective study in Hong Kong to evaluate the toxicity of this regimen in Chinese patients. Methods: Between January 2007 and May 2008 76 female Chinese patients with resected stage I–III operated invasive breast cancer were treated with 4 cycles of TC (75 and 600 mg/m2, respectively, administered i.v. every 3 weeks for four cycles) in two public regional cancer centers of Hong Kong. A total of 24 (32%) patients also received primary prophylactic ciprofloxacin (500 mg twice daily, day 5–14). Chemotherapy-related toxicities were graded by the CTCAE version 3.0. Results: The median age was 50 (range 26–67). A total of 68 (89%) patients successfully completed four cycles of chemotherapy. 72 (95%) and 16 (21%) patients developed grade 3–4 neutropenia and febrile neutropenia (FN) infection, respectively, in one or more cycles. However, no grade 3–4 anemia or thrombocytopenia events were observed. Other grade 3–4 non-hematological toxicities were also uncommon, apart from allergic reactions in two (3%) patients. No viral reactivation was observed among the 8 hepatitis B carriers. Patients with prophylactic ciprofloxacin had less grade 3–4 FN infection (13% vs 25%, P = 0.214) and a higher chance of receiving the full scheduled dose (88% vs 62%, P = 0.045) than patients without. Conclusion: The myelotoxicity of TC was substantially higher in Chinese patients compared with non-Chinese patients in developed countries. Routine prophylactic measures are recommended to maintain the dose levels and reduce the risk of FN.

Background. The aim of this analysis was to evaluate the outcomes of patients with nasopharyngeal carcinoma (NPC) treated primarily by external beam irradiation (ERT) and to explore for possible ways to improve the treatment results. Methods. One thousand seventy patients with nonmetastatic NPC treated from 1990 to 1998 were retrospectively analyzed. The distribution according to the Union Internationale Contre le Cancer (UICC) (1997 edition) staging system at initial diagnosis was as follows: stage I, n = 113; stage IIA, n = 38; stage IIB, n = 360; stage III, n = 306; stage IVA, n = 136; stage IVB, n = 117; T1, n = 284; T2a, n = 88; T2b, n = 398; T3, n = 149; T4, n = 151; N0, n = 321; N1, n = 393; N2, n = 238; N3a, n = 29; N3b, n = 89. Two hundred eight patients were given neoadjuvant chemotherapy. Ninety-seven patients were diagnosed with locally persistent disease and were salvaged with high dose rate intracavitary brachytherapy. Multivariate analysis was performed with the Cox regression proportional hazards model. Results. The 5-year actuarial local failure–free survival, regional failure–free survival, distant metastasis–free survival, progression-free survival, cancer-specific survival, and overall survival rates were 80.9%, 93.3%, 77.2%, 62.7%, 71.4%, and 66.5%, respectively. Isolated distant metastasis occurred in 191 patients (18%). The distributions were as follow: stage I, 2.1% (two of 95); stage IIA, 5.7% (two of 35); stage IIB, 14.9% (45 of 302); stage III, 26.4% (62 of 235); stage IVA, 40% (40 of 100); stage IVB, 47.1% (40 of 85). Results of the multivariate analysis of various clinical endpoints were discussed. By studying these failure patterns, it is hoped that we could refine future treatments according to the failure patterns of patients with different risks of locoregional and distant failure. Conclusions. The 18% incidence of isolated distant metastasis is too high to be ignored. Maximizing the local control and minimizing the risk of distant metastasis and late complications should be the key objectives in designing future clinical trials. © 2005 Wiley Periodicals, Inc. Head Neck27: XXX–XXX, 2005

Background Alveolar rhabdomyosarcoma (RMS) has a high risk for local and distal failure. Multimodal management of a patient with alveolar RMS of the cervix uteri is outlined. Case A 39-year-old woman suffered from alveolar RMS of the cervix without involvement of uterus and parametrium. She was treated with total hysterectomy and left salpingo-oophorectomy. Systemic chemotherapy and pelvic irradiation were also offered. She remains in clinical remission 3 years after presentation. Conclusion Postoperative chemotherapy and irradiation could be effective treatments for alveolar rhabdomyosarcoma of the cervix in adult patients.

This prospective study aimed at investigating the efficacy and safety of the concurrent use of celecoxib (CXB) with 5-fluorouracil, epirubicin and cyclophosphamide (FEC), followed by docetaxel (T) in the neoadjuvant setting.A total of 64 invasive breast cancer patients were recruited in the N001 Phase II, multicenter, open-label, single-arm study to receive four cycles of FEC (500, 100, 500 mg/m(2)) followed by four cycles of T (100 mg/m(2)) with concurrent CXB (200 mg b.i.d.) as neoadjuvant therapy (NAT). The combined chemotherapies were administered on day 1 of each cycle every 3 weeks. Primary endpoints were pathologic complete response (pCR) rate and objective response rate (ORR). Quasi-pCR (QpCR), pCR and near pCR (npCR) were discussed considering their similar survival outcomes. ORR included clinical complete response (cCR) and clinical partial response (cPR). Secondary endpoints included safety, breast conservation rate and disease-free survival.Between February 2006 and January 2010, 57 of 64 evaluable patients with luminal A (n = 35, 61.4%), luminal B (n = 12, 21.1%), HER-2 positive (n = 8, 14%) and triple-negative (n = 2, 3.5%) breast cancer completed NAT and surgery. QpCR rate was observed in 18 (31.6%) patients. Exclusive of triple-negative subtype, pCR (p = 0.761) did not differ compared to other subtypes, while npCR (p = 0.043) exhibited a difference. Patients with HER-2 overexpression had a significantly higher QpCR than those of the disease attribute (10/20 vs 8/37, p = 0.029). After NAT, 43 (75.4%) and 13 (22.8%) patients achieved cCR and cPR, respectively. Patients responding to FEC were more likely to achieve a better ORR after subsequent T (p = 0.004). Over 80% of all patients received breast-conserving therapy (BCT) after receiving NAT, and 11 of 14 (78.6%) patients with T3 tumor at diagnosis became eligible for BCT after NAT. A total of 60 patients completed ≥ 6 cycles of NAT, followed by surgery; at a median follow-up of 50 months, 80% of the patients are disease-free. Neither drug-induced life-threatening toxicity nor cardiotoxicity was observed.Neoadjuvant use of FEC-T with concurrent CXB is active and safe for treatment of operable invasive breast cancer. The ORR was higher, but QpCR was comparable to other studies. Most patients are still disease-free, and BCT became an option for the females. Further clinical and translational studies on the use of cyclooxygenase-2 inhibitors with neoadjuvant chemotherapy are warranted.

e12507Background: Inhibition of mTOR, a downstream mediator of the PI3K/AKT signaling pathway, is a significant anti-cancer approach in response to PI3K/AKT activation, as demonstrated clinically w...

Introduction Little information is available on the outcomes of Hodgkin's lymphoma in Chinese patients. We analyzed the clinical and histopathological characteristics, treatment types, clinical course and treatment outcomes of Hong Kong Chinese patients. Material and methods Patients with Hodgkin's lymphoma diagnosed from January 1991 to December 2010 were recruited. A retrospective analysis of these patients was performed. Results Sixty-seven Chinese patients (38 males and 29 females) were identified and the median age was 36 (range 16–80). Nodular sclerosis was the most common histology (54%), followed by mixed cellularity (36%). Twenty-four patients had early favorable, 20 patients had early unfavorable and 23 patients had advanced-stage diseases. The most common presentation was palpable lymph node or mass (85%) followed by fever, weight loss, night sweating and mediastinal mass. Ninety percent of patients received chemotherapy and 40% received radiotherapy as consolidation. Seven patients with stage I lymphoma received radiotherapy alone. ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) was the most commonly used chemotherapeutic regimen. Following treatment, 87% of patients achieved complete remission. Six patients relapsed after first remission and 3 achieved second remission after re-induction therapy. The 5-year overall survival of the entire cohort was 89% and the freedom from treatment failure (FFTF) at 5 years was 82%. The 5-year overall survival rate for early favorable, early unfavorable and advanced stages was 95.7%, 95.0% and 74.7%, respectively. Conclusions Despite the relatively low incidence of Hodgkin's lymphoma in Hong Kong Chinese, the treatment outcomes are comparable to Caucasian patients.

The integrated care pathway is used in end-of-life care to improve quality of care; the Liverpool Care Pathway (LCP) has been used in Europe and North America. Tuen Mun Hospital is a regional hospital in Hong Kong, China. The End-of-life Care Pathway (ECP) based on the concepts used in the Liverpool Care Pathway, was developed, with modification to suit the local condition. Criteria for entry onto the ECP were that the multidisciplinary team agreed the patient was dying, and was at least two of the following: bedbound; semi-comatose; only able to take sips of fluid; no longer able to take tablets. The ECP template replaced all other inpatient documents. The ECP was implemented in the palliative care unit for terminal cancer patients. An audit was performed to review the result. Fifty-one Chinese patients were included in the audit with mean age 64. The median duration of ECP use was 24 hours. All patients had current medication assessed and non-essential drugs were discontinued. The audit result suggested integrated care pathway in end-of-life care could be implemented successfully in an Oriental culture. The acceptance of using the ECP as a standard clinical practice takes time and education. Appropriate template design and supervision are the keys to success.

Background High dose rate (HDR) interstitial brachytherapy of the oral tongue is a new treatment modality. Our study evaluates the outcomes of patients with early stage oral tongue cancer as treated by HDR interstitial implant. Methods We reviewed the records of 19 patients who were seen between 1994 and 2000 with carcinoma of the oral tongue and whose primary tumors were treated solely with interstitial implant using HDR remote afterloading technique. Ten patients had T1 N0 disease, and the remaining 9 had T2 N0 disease. Elective neck treatment was withheld for 12 patients. The remaining seven patients had ipsilateral elective neck dissection. The male–female ratio was 1:0.9, and the median age was 60 years (range, 32–81 years). The median follow-up time was 43 months (range, 6–78 months). The afterloading catheters were positioned by the submandibular approach with the assistance of a template set. Fifteen patients had single planar implants, and the remaining four had double planar implants. The median number of catheters inserted was 5 (range, 4–9). The median dose given was 55 Gy in 10 fractions over 6 days. The minimal interfraction interval was 7 hours for the first 7 patients and was extended to 8 hours for the other 12. Mandibular shields were inserted before treatment. Results The mucositis lasted for 6 to 20 weeks (median, 9 weeks). One patient had local failure, and the 4-year local failure-free survival rate was 94.7%. Three of the 12 patients without elective neck treatment had ipsilateral regional failure develop. They were salvaged by neck node dissection and regionally remained in control. One patient with multiple nodal metastases and extracapsular spread had biopsy-proven liver metastases and died 6 months after implant. One of the seven patients who were treated with elective neck dissection had multiple nodal metastases and extracapsular spread. She was treated with postoperative radiotherapy to the neck. She died 30 months after implant with evidence of regional and distant failure. One patient treated with double planar implant had grade II necrosis of the soft tissue and bone develop. The necrosis resolved with conservative treatment. Another four patients had small area of soft tissue deficit of the tongue attributed to aggressive debulking or biopsy before brachytherapy. Conclusions Our experience in treating early stage tongue cancer with HDR remote afterloading technique is encouraging, because it gives a local control rate of 94.7% at 4 years with acceptable morbidity. Further studies are eagerly awaited to delineate the optimum schedule for this new treatment modality. © 2002 Wiley Periodicals, Inc. Head Neck 24: 274–281, 2002; DOI 10.1002/hed.10021