Roger K.C. Ngan

Subtype-specific incidence rates of lymphoid malignancies in Hong Kong compared to the United States, 20012010

Clinical studies of lymphoid malignancies (LMs) have suggested that the descriptive patterns of LMs differ in East Asia compared to Western populations. However, there are very limited available data on population-based, subtype-specific incidence rates of LMs in the East Asian population, particularly in Chinese. Using data from the Hong Kong (HK) Cancer Registry and United States (U.S.) SEER Program, we calculated and compared age-adjusted incidence rates of LM subtypes in HK to those in Whites and Asians living in the U.S. Overall and sex-specific rates were calculated for the period 2001-2010. The incidence of most subtypes was low in the HK population, with rates <1 case per 100,000 for all subtypes except for diffuse large B-cell lymphoma (3.26/100,000) and plasma cell neoplasms (1.99/100,000). Age-adjusted incidence rates of all evaluated B-cell subtypes were significantly higher in U.S. Whites compared to HK, with standardized rate ratios (SRRs) ranging from 1.6 (Burkitt lymphoma) to 9.1 (chronic lymphocytic leukemia/small lymphocytic lymphoma). Rates in U.S. Asians were generally intermediate to those in U.S. Whites and HK. Conversely, rates of extranodal NK/T-cell lymphoma were significantly lower in both U.S. Whites (SRR=0.2) and U.S. Asians (SRR=0.5) compared to HK. Our data provide new insight into the subtype-specific patterns of LMs in the Chinese population, and suggest the need for etiological studies of LMs in the East Asian population to elucidate the factors responsible for these differences in the geographic incidence patterns.

Clinicopathological features and outcome of late relapses of natural killer cell lymphomas 10-29 years after initial remission.

Natural killer (NK)-cell lymphomas are aggressive and relapses occur early. Late relapses are exceptional. Ten relapses 17.5 (11-29) years after first complete remission (CR1) were analyzed. Initial diseases were stage-I (nasal, n = 8; tonsil, n =1; ileum, n =1), treated with radiotherapy (n = 6), combined radiotherapy/chemotherapy (n =3), and chemotherapy (n =1). Relapse occurred at the same (nasal, n = 6; tonsil, n = 1), adjacent (initial: nasal, relapse: palate; n =1) or distant (n =2) sites. Five patients died soon afterwards. Four patients remitted with chemotherapy, two remaining in CR2 (3, 14 years). This series documented the rare late relapses in NK-cell lymphomas, which may still respond to salvage therapy.

Efficacy and tolerability of trastuzumab emtansine in advanced human epidermal growth factor receptor 2–positive breast cancer

INTRODUCTIONnThe 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.nnnMETHODSnThis 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.nnnRESULTSnAmong 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.nnnCONCLUSIONSnIn 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.

Risk, pattern and survival impact of second primary tumors in patients with nasopharyngeal carcinoma following definitive intensity-modulated radiotherapy

Second primary tumor (SPT) is a serious late complication after definitive radiotherapy for nasopharyngeal carcinoma (NPC). We evaluated the incidence, pattern, risk factors and survival impact of SPT in NPC patients following definitive intensity‐modulated radiotherapy (IMRT).

A prospective multicenter phase II trial of induction chemotherapy followed by bio-chemoradiotherapy for locally advanced recurrent nasopharyngeal carcinoma

PURPOSEnTo evaluate, in a phase 2 study, whether induction docetaxel, cisplatin, and fluorouracil (TPF) followed by weekly docetaxel and cetuximab in concurrence with intensity modulated radiation therapy can improve the treatment outcome for patients with advanced locally recurrent nasopharyngeal carcinoma (rNPC).nnnMETHODS AND MATERIALSnThirty-three patients with rNPC (T3-T4, N0-N1, M0) were recruited. Of these, 19 patients (57.6%) had stage rT3 recurrence, and the rest had stage rT4. Eight patients also had rN1 at the time of relapse. Treatment outcomes and safety were evaluated.nnnRESULTSnAmong these 33 patients, 1 died after 1 cycle of TPF, 5 patients withdrew from the study during the induction period because of grade ≥3 toxicities; 27 patients completed the whole course of treatment, but 1 died before any assessment could be made. The median follow-up period was 28.5xa0months. The progression-free survival and overall survival at 3xa0years for the whole group were 35.7% and 63.8%, respectively. Among the 26 patients who could be assessed after treatment, the complete response rate was 30.8%, and the locoregional control rate at 3xa0years was 49.2%. Temporal lobe necrosis (TLN) developed in 8 cases. The rates of grade ≥3 hearing loss, soft tissue necrosis, dysphagia, and trismus were 30.8%, 15.4%, 11.5%, and 19.2%, respectively. Overall, 5 patients died owing to acute (1 after cycle 1 TPF and 1 after completion of bio-chemoradiotherapy) or late (2 epistaxis and 1 TLN) treatment-related complications.nnnCONCLUSIONSnThe proposed salvage treatment regimen for advanced locally recurrent NPC could achieve a better treatment outcome than seen in previous studies. However, poor tolerability of induction TPF and the high rate of TLN limit its applicability outside clinical trials.

Abstract 5206: Recent incidence trends of lymphoid malignancies in Hong Kong, 2001-2010

Incidence trends of lymphoid malignancies in the United States (U.S.) have been well-characterized based on analyses of data from the Surveillance, Epidemiology, and End Results Program. These analyses showed marked increases in incidence rates of non-Hodgkin lymphoma (NHL) in the early to mid-1990s, with some evidence that rates have begun to level off in the recent decade. In contrast, there are limited published data on trends in rates of lymphoid malignancies in the Chinese population, particularly for subtypes. Such analyses may provide insight into geographic differences in the descriptive epidemiological patterns of these neoplasms as well as etiological hypotheses. To explore recent trends in incidence rates in HK, yearly age-adjusted incidence rates and annual percent changes (APCs) were calculated using available data over the period 2001-2010 for overall lymphoid malignancies, overall B-cell neoplasms not including Hodgkin lymphoma (HL), overall NK or T-cell tumors, HL, plasma cell neoplasms (PCN), and specific NHL B-cell subtypes that were most common in the HK population over this time period, including diffuse large B-cell lymphoma (DLBCL), marginal zone lymphoma (MZL), and follicular lymphoma (FL). The incidence of overall lymphoid malignancies showed a steady increase in HK over the period 2001-2010 with an APC of +1.4% (95% CI = + 0.4%, + 2.3%). A steady rate of increase was further observed over the ten year period for overall B-cell neoplasms not including HL (APC = +1.6%, 95% CI = + 0.4%, + 2.9%), whereas the incidence of overall T- and NK/T cell neoplasms showed no significant fluctuation over the ten year period (APC = -1.1%, 95% CI = -3.5%, +1.5%). For the most common subtypes diagnosed in HK during the study period, an increasing trend of HL was observed over the years 2004-2010 only (APC = + 10.5%, 95% CI = + 4.9%, + 16.4%) based on the best-fitting model that included one joinpoint, and stable but non-significant rates of increase for DLBCL (APC = + 1.5%, 95% CI = - 0.7%, + 3.6%), PCN (APC = + 1.2%, 95% CI = -0.2%, + 2.6%), and FL (APC = + 2.7%, 95% CI -0.5%, 6.0%) were also observed, all over the period 2001-2010. Conversely, incidence rates of MZL showed no significant fluctuation over the study period (APC = -1.0%, 95% CI = -2.9%, +0.8%). The overall trends observed during even this relatively short time-period suggest that the rate of several lymphoid malignancies in HK may be beginning to shift in the direction of rates that were observed among individuals living in the U.S. Additional analyses of population-based registry data from other regions in East Asia, especially over longer time-periods, are needed to replicate and extend these findings. Further, our results support the need for etiological studies of lymphoid malignancies in this population, particularly as it relates to environmental, occupational and lifestyle risk factors that might influence disease rates and the genetic risk factors that potentially interact with them. Citation Format: Bryan A. Bassig, Wing-Yan Au, Oscar Mang, Roger Ngan, Lindsay M. Morton, Dennis K.M. Ip, Wei Hu, Tongzhang Zheng, Wei Jie Seow, Jun Xu, Nathaniel Rothman, Qing Lan. Recent incidence trends of lymphoid malignancies in Hong Kong, 2001-2010. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5206.

Abstract 5207: Comparison of subtype-specific incidence rates of lymphoid malignancies in Hong Kong and the United States

Clinical studies of lymphoid malignancies (LMs) have suggested that the descriptive patterns of these neoplasms differ in East Asia compared to Western populations. However, there are very limited available data on population-based, subtype-specific incidence rates of LMs in the East Asian population, particularly in Chinese. Using data from the Hong Kong (HK) Cancer Registry and the United States (U.S.) Surveillance, Epidemiology, and End Results Program, we calculated and compared age-adjusted incidence rates of LM subtypes in HK to those in Whites and Asians living in the U.S. Overall and sex-specific rates were calculated for the period 2001-2010. In order to formally compare the incidence rates between HK and the U.S., standardized rate ratios (SRRs) were calculated comparing the age-adjusted rates of each subtype for U.S. Whites and U.S. Asians in the SEER 13 database to HK. The incidence of most subtypes was low in the HK population, with rates Citation Format: Nathaniel Rothman, Bryan A. Bassig, Wing-Yan Au, Oscar Mang, Roger Ngan, Lindsay M. Morton, Dennis K.M. Ip, Wei Hu, Tongzhang Zheng, Wei Jie Seow, Jun Xu, Qing Lan. Comparison of subtype-specific incidence rates of lymphoid malignancies in Hong Kong and the United States. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5207.

Abstract 3153: A new circulating plasma/serum Epstein-Barr virus (EBV) DNA test by locked nucleic acid (LNA) PCR technique with enhanced sensitivity in diagnosis & monitoring of patients suffering from nasopharyngeal carcinoma (NPC) and other EBV associated malignancies

Circulating plasma/serum Epstein-Barr virus (EBV) test has been established as routine first line diagnostic test for Nasopharyngeal Carcinoma (NPC). This real time quantitative PCR test is useful in primary diagnosis of NPC as well as monitoring distant metastases of NPC to lung, liver and distant lymph nodes. However, it is still lacking sensitivity in diagnosis of early stage I/II NPC and local relapse in nasopharynx. Detection sensitivity of this PCR test relies on detecting small fragments of circulating EBV DNA shed into the blood stream from NPC tumor lesions which underwent apoptosis/necrosis. Previous literature already showed that the smaller the molecular size of the circulating EBV DNA targets detected, the higher the detection sensitivity. Using Locked Nucleic Acid (LNA) PCR technique, we have designed a new set of LNA primers for PCR amplification of a much smaller EBV gene target (BamH1-W DNA at 46 bp) than the conventional EBV gene target (BamH1-W at 76 bp). Using this LNA marker, we successfully achieved detection sensitivity of 95.7% in 46 NPC patients (44/46 positive) and detection specificity of 98.3% in 59 normal blood screening subjects (58/59 negative). 89.1% (i.e. 41/46) of the NPC patients had higher EBV DNA gene copies per mL in the LNA marker than the conventional marker. Folds of gene copies per mL of increase of LNA marker over those of conventional marker varied from 6 folds up to 3800 folds in 27/46 NPC patients. The results were confirmed in a validation set of 141 NPC patients (113/141) in a multicenter study under the umbrella of NPC Area of Excellence (AoE) program in Hong Kong with 79.6% (113/142) of NPC patients having higher gene copies per mL of LNA marker than the conventional marker initially tested. On longitudinal monitoring of the new LNA marker in 9 NPC patients for a period of 4.9 months to 5.6 months, higher sensitivity of detection was also achieved at disease onset, during the clinical course of disease and at distant metastases (2/9) than the conventional marker. Three patients with Lymphoepithelioma Like Carcinoma of Lung (LELC) and 3 patients with extra nodal nasal NK/T cell lymphoma were monitored from 3 months to 19.3 months. Detection sensitivity was also higher in the new LNA marker in 3/3 LELC and 1/2 NK/T lymphoma with disease progression whereas 1 NK/T lymphoma with remission had LNA marker remained negative. With such enlightening findings, we are expanding the scope of this new test to many more NPC patients as well as other EBV associated malignancies. We are also recruiting patients in embarking on a large scale prospective study. Citation Format: Timothy T.C. Yip, Hazel Y.Y. Kwok, Sharon S.Y. You, Dora L.W. Kwong, Alvin H.W. Fong, W.W. Cheng, Christopher Lai, Anthony C.C. Shek, Victor W.S. Ma, Maria LiLung, Roger K.C. Ngan. A new circulating plasma/serum Epstein-Barr virus (EBV) DNA test by locked nucleic acid (LNA) PCR technique with enhanced sensitivity in diagnosis & monitoring of patients suffering from nasopharyngeal carcinoma (NPC) and other EBV associated malignancies. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3153.