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Background The extent of thyroid surgery remains controversial for differentiated thyroid cancers (DTCs) that measure more than 1 cm but are not considered high risk. This study aimed to compare survival outcomes between hemithyroidectomy (HT) and total thyroidectomy (TT) in non-high-risk DTCs. Methods A population-based retrospective cohort of patients with non-high-risk DTCs more than 1 cm undergoing HT or TT between 1997 and 2017 in a territory with 41 public hospitals and clinics serving a population of 7 million was analysed. Multivariable Cox proportional hazards regression models adjusted for patient demographics and clinical parameters were used to compare the overall, disease-specific, and recurrence-free survival between TT and HT. Risks of postoperative complications were compared between the two groups. Results A total of 4771 patients (HT, 1368; TT, 3403) underwent thyroid surgery as a primary treatment. Median (range) follow-up was 117 (range: 72–179) months. Patients in the TT and HT groups had comparable risks of overall survival (HR 0.87; 95 per cent c.i. 0.73 to 1.04; P = 0.119) and disease-specific survival (HR 0.85; 95 per cent c.i. 0.52 to 1.40; P = 0.518). The TT group had better recurrence-free survival (HR 0.37; 95 per cent c.i. 0.26 to 0.52; P < 0.001) than the HT group. The temporary and permanent hypoparathyroidism rates in TT group were 14.96 per cent and 7.49 per cent respectively; none were reported in the HT group. Conclusions Despite the comparable overall and disease-specific survivals, TT was associated with better recurrence-free survival than HT in a 10-year follow-up. This was at the expense of higher surgical morbidity rate in TT.

Developed as an antidiabetic drug, recent evidence suggests that several sodium-glucose co-transporter 2 inhibitors (SGLT2i), especially canagliflozin and dapagliflozin, may exhibit in vitro and in vivo anticancer activities in selected cancer types, including an inhibition of tumor growth and induction of cell death. When used in combination with chemotherapy or radiotherapy, SGLT2i may offer possible synergistic effects in enhancing their treatment efficacy while alleviating associated side effects. Potential mechanisms include a reduction of glucose uptake into cancer cells, systemic glucose restriction, modulation of multiple signaling pathways, and regulation of different gene and protein expression. Furthermore, preliminary clinical findings have reported potential anticancer properties of canagliflozin and dapagliflozin in patients with liver and colon cancers respectively, with reference to decreases in their tumor marker levels. Given its general tolerability and routine use in diabetes management, SGLT2i may be a good candidate for drug repurposing in cancer treatment and as adjunct to conventional therapies. While current evidence reveals that only certain SGLT2i appear to be effective against selected cancer types, further studies are needed to explore the antitumor abilities of each SGLT2i in various cancers. Moreover, clinical trials are called for to evaluate the safety and feasibility of introducing SGLT2i in the treatment regimen of patients with specific cancers, and to identify the preferred route of drug administration for targeted delivery to selected tumor sites.

Radioactive iodine is given after total thyroidectomy for remnant ablation or treatment of residual/metastatic disease. The decision and dose of radioactive iodine should be in a personalized and patient-specific approach, taking account the clinical-pathological features, risk stratification, patient's preference, and facilities of the institutions. We review the principles and use of radioactive iodine in differentiated thyroid cancer.

Most patients with well-differentiated thyroid cancers (WDTC) are adequately treated with surgery, radioactive iodine, and TSH suppression by thyroxine. External radiotherapy (ERT) is reserved for selected cases and for older patients. Some of the indications for ERT to neck include adjuvant treatment for gross or microscopic disease after surgery, palliation of locally advanced unresectable tumor, or as salvage for recurrent disease which is not amenable to surgery or does not uptake radioactive iodine. High radiation dose of at least 60Gy is required for locoregional control of gross or microscopic residual disease. As even patients with recurrent or metastatic disease can have long survival, it is important to minimize late radiation-induced morbidity without compromising local control. Modern ERT technique like intensity-modulated radiotherapy allows high radiation dose to be delivered to the large, complex target volume while protecting the adjacent critical normal structures like the trachea, larynx, esophagus, and cervical spinal cord.

Patients with radioactive iodine (RAI) refractory locally advanced or metastatic differentiated thyroid cancer have a poor prognosis. This article reviews the definition of RAI-refractory thyroid cancer and the management approach. Watchful waiting should be considered for patients with asymptomatic and non-progressive disease, while oral targeted agent with tyrosine kinase inhibitors can be considered for patients who are symptomatic or whose disease would cause irreversible complications if treatment has not been initiated. Since these targeted agents only improve disease-free survival and are associated with adverse events, physicians should assess both clinical and tumor factors carefully to decide on the right timing of start of palliative treatment.

Background The relationship between good early control of thyroid hormone levels after thyroidectomy for Graves’ disease (GD) and subsequent risks of mortality and morbidities is not well known. The aim of this study was to examine the association between thyroid hormone levels within a short interval after surgery and long-term mortality and morbidity risks from a population-based database. Methods Patients with GD who underwent complete/total thyroidectomy between 2006 and 2018 were selected from the Hong Kong Hospital Authority clinical management system. All patients were classified into three groups (euthyroidism, hypothyroidism, and hyperthyroidism) according to their thyroid hormone levels at 6, 12, and 24 months after surgery. Cox proportional hazards models were performed to compare the risks of all-cause mortality, cardiovascular disease (CVD), Graves’ ophthalmopathy, and cancer. Results Over a median follow-up of 68 months with 5709 person-years, 949 patients were included for analysis (euthyroidism, n = 540; hypothyroidism, n = 282; and hyperthyroidism, n = 127). The hypothyroidism group had an increased risk of CVD (HR = 4.20, 95 per cent c.i. 2.37 to 7.44, P Conclusions This study showed a higher risk of CVD in postsurgical hypothyroidism and a higher risk of cancer in hyperthyroidism compared with achieving euthyroidism early after thyroidectomy. Patients who were euthyroid at 6 months and 12 months had better outcomes than those achieving euthyroidism only at 6 months or 12 months. Attaining biochemical euthyroidism early after thyroidectomy should become a priority.

Aims/Introduction There is uncertainty about the direct medical costs of type 2 diabetes patients with cancers. Materials and Methods A population‐based retrospective cohort of 99,915 type 2 diabetes patients from the Hong Kong Hospital Authority between 2006 and 2017 was assembled. A total of 16,869 patients who had an initial cancer diagnosis after type 2 diabetes diagnosis were matched with 83,046 patients without cancer (controls) using a matching ratio of up to one‐to‐five propensity score‐matching method. Patients were divided into four categories according to life expectancy. Healthcare service utilization and direct medical costs during the index year, subsequent years and mortality year were compared between patients with and without cancer in each category. Results Medical costs of cancer patients in the index year ranged from $US27,533 for patients who died in 3 years. Cancer patients had significantly greater expenditures than controls in the index year (all P 3 years after the index year ($US32,558 vs $US28,260). For patients in both groups, patients who survived >3 years had significantly lower costs than those who died in 90% of the medical costs for both groups in the mortality year. Conclusions Type 2 diabetes patients with cancers incurred greater medical costs in the diagnosis, ensuing and mortality years than type 2 diabetes patients without cancers., Type 2 diabetes increases the risks of cancers, which have a tremendously heavy economic burden. Type 2 diabetes patients with cancers had significantly greater costs in the cancer diagnosis year, ensuing years and mortality year. Current type 2 diabetes economic models can be further refined by incorporating cancer as a model event subgraph (b), the p‐value for year of mortality should be 0.594 instead of p < 0.001.

Objective This study compared the efficacy of PF-based and CROSS-based neoadjuvant chemoradiotherapy for ESCC. Background PF-based regimen has been a standard regimen for ESCC, but it has been replaced by the CROSS regimen in the past few years, despite no prospective head-to-head comparative study has been performed. Methods This is a single center retrospective study. Records of all ESCC patients who have received neoadjuvant PF with 40 Gy radiotherapy in 20 daily fractions (PFRT Group) or CROSS with 41.4 Gy radiotherapy in 23 daily fractions (CROSS Group) during the period 2002 to 2019 were retrieved. Propensity score matching (1:1) was performed to minimize baseline differences. The primary and secondary endpoints were overall survival and clinicopathological response. Subgroup analysis ("CROSS Eligibility") was performed based on tumor length, cT-stage, cM-stage, age, and performance status. Results One hundred (out of 109) patients (CROSS group) and propensity score matched 100 (out of 210) patients (PFRT group) were included. Esophagectomy rates in CROSS and PFRT group were 69% and 76%, respectively (P = 0.268). R0 resection rates were 85.5% and 81.6% (P = 0.525) and the pathological complete remission rates were 24.6% and 35.5% (P = 0.154). By intention-to-treat, the median survival was 16.7 and 32.7 months (P = 0.083). For "CROSS Eligible subgroup," the median survival of the CROSS and PFRT group was 21.6 versus 44.9 months (P = 0.093). Conclusions There is no statistically difference in survival or clinicopathological outcome between both groups, but the trend favors PFRT. Prospective head-to-head comparison and novel strategies to improve the outcomes in resectable ESCC are warranted.

Preoperative chemoradiation (CROSS regimen) has been widely adopted worldwide. The survival advantage imparted is especially impressive for oesophageal squamous cell carcinoma (OSCC). This study aimed at investigating the efficacy of the CROSS regimen in real-world scenario. This is a retrospective study of all patients with OSCC intended for preoperative treatment using the CROSS regimen during 2012–2017. Patients were divided into two groups: those within the selection criteria in the CROSS trial and those beyond criteria, namely age > 75 years old, tumour length > 8 cm or clinical M1 stage of lymph node involvement (AJCC 6th edition). Clinical outcome and survival data were compared. Eighty-eight patients were included. There were 46 patients in the “CROSS eligible” group and 42 in the “CROSS ineligible” group. By intention-to-treat, the estimated median survival was 24.2 months vs. 12.7 months, respectively (p = 0.047). The results were much inferior compared to that published in the original CROSS trial. Univariable and multivariable analyses showed tumour length and resectability as independent variables affecting survival. In a real-world scenario, the clinical outcome remains suboptimal and the excellent results in the trial setting were not reproducible in this Asian cohort. Patient selection is one key element accountable for the difference. The efficacy of the CROSS regimen may not be adequate for patients with more advanced disease. The optimal multimodal therapy for this group of patients remains undefined.

Developed as an antidiabetic drug, recent evidence suggests that several sodium-glucose co-transporter 2 inhibitors (SGLT2i), especially canagliflozin and dapagliflozin, may exhibit in vitro and in vivo anticancer activities in selected cancer types, including an inhibition of tumor growth and induction of cell death. When used in combination with chemotherapy or radiotherapy, SGLT2i may offer possible synergistic effects in enhancing their treatment efficacy while alleviating associated side effects. Potential mechanisms include a reduction of glucose uptake into cancer cells, systemic glucose restriction, modulation of multiple signaling pathways, and regulation of different gene and protein expression. Furthermore, preliminary clinical findings have reported potential anticancer properties of canagliflozin and dapagliflozin in patients with liver and colon cancers respectively, with reference to decreases in their tumor marker levels. Given its general tolerability and routine use in diabetes management, SGLT2i may be a good candidate for drug repurposing in cancer treatment and as adjunct to conventional therapies. While current evidence reveals that only certain SGLT2i appear to be effective against selected cancer types, further studies are needed to explore the antitumor abilities of each SGLT2i in various cancers. Moreover, clinical trials are called for to evaluate the safety and feasibility of introducing SGLT2i in the treatment regimen of patients with specific cancers, and to identify the preferred route of drug administration for targeted delivery to selected tumor sites.

Background The aim of this study was to compare long-term mortality, morbidity, and cumulative healthcare costs between antithyroid drugs, radioactive iodine, and surgical treatment for patients with persistent or relapsed Graves’ disease. Methods Data on patients with persistent or relapsed Graves’ disease between 2006 and 2018 were retrieved from the Hong Kong Hospital Authority. Hazard ratios (HRs) estimated by Cox proportional hazards regression models were used to compare the risks of all-cause mortality, cardiovascular disease, atrial fibrillation, psychological disease, Graves’ ophthalmopathy, and cancer across treatment groups. The 10-year healthcare cost and change in co-morbidity status were also estimated. Results Over a median follow-up of 79 months (22 636 person-years), a total of 3443 patients (antithyroid drug 2294, radioactive iodine 755, surgery 394) were analysed. Compared with antithyroid drug treatment, surgery was associated with significantly lower risks of all-cause mortality (HR 0.40, 95 per cent c.i. 0.36 to 0.45), cardiovascular disease (HR 0.54, 0.48 to 0.60), atrial fibrillation (HR 0.11, 0.09 to 0.14), psychological disease (HR 0.85, 0.79 to 0.92), Graves’ ophthalmopathy (HR 0.09, 0.08 to 0.10), and cancer (HR 0.56, 0.50 to 0.63). Patients who underwent surgery also had a lower risk of all outcome events than those in the radioactive iodine group. The 10-year direct cumulative healthcare cost was €14 754 for surgery compared with €17 390 for antithyroid drugs, and €17 918 for the radioactive iodine group. Conclusion Patients who underwent surgery for persistent or relapsed Graves’ disease had lower risks of all-cause mortality and analysed morbidities. The 10-year cumulative healthcare cost in the surgery group was lowest among the three treatment alternatives.

Background The long-term outcomes of first-line choice among anti-thyroid drug (ATD), radioactive iodine (RAI) and thyroidectomy for Graves' disease (GD) patients remain unclear. Objective To compare the long-term morbidity, mortality, relapse, and costs of GD patients receiving first-line treatment. Methods A population-based retrospective cohort of GD patients initiating first-line treatment with ATD, RAI, or thyroidectomy as a first-line primary treatment between 2006 and 2018 from Hong Kong Hospital Authority was analyzed. Risks of all-cause mortality, cardiovascular diseases (CVD), atrial fibrillation (AF), psychological disease, diabetes, and hypertension were estimated using Cox proportional hazards regression models. The 10-year healthcare costs, change of comorbidities, and risk of relapse were compared across treatments. Results Over a median follow-up of 90 months with 47,470 person-years, 6385 patients (ATD, 74.93%; RAI, 19.95%; thyroidectomy, 5.12%) who received first-line treatment for GD were analyzed. Compared with ATD group, patients who had undergone surgery had significantly lower risks of all-cause mortality (HR = 0.363, 95%CI = 0.332-0.396), CVD (HR = 0.216, 95%CI = 0.195-0.239), AF (HR = 0.103, 95%CI = 0.085-0.124), psychological disease (HR = 0.279, 95%CI = 0.258-0.301), diabetes (HR = 0.341, 95%CI = 0.305-0.381) and hypertension (HR = 0.673, 95%CI = 0.632-0.718). Meanwhile, RAI group was also associated with decreased risks of all-cause mortality (HR = 0.931, 95%CI = 0.882-0.982), CVD (HR = 0.784, 95%CI = 0.742-0.828), AF (HR = 0.622, 95%CI = 0.578-0.67) and psychological disease (HR = 0.895, 95%CI = 0.855-0.937). The relapse rate was 2.41% in surgery, 75.60% in ATD, and 19.53% in RAI group. The surgery group was observed with a significant lower CCI score than the other two groups at the tenth-year follow-up. The mean 10-year cumulative healthcare costs in ATD, RAI, and surgery group was US$23915, US$24260, and US$20202, respectively. Conclusions GD patients who received surgery as an initial treatment appeared to have lower chances of all-cause mortality, CVD, AF, psychological disease, diabetes and hypertension in the long-term when compared to those treated with ATD or RAI. The surgery group had the lowest relapse and direct healthcare costs among the three treatment modalities. This long-term cohort study suggested surgery may have a larger role to play as an initial treatment for GD patients.

This study compared the efficacy of PF-based and CROSS-based neoadjuvant chemoradiotherapy for ESCC.PF-based regimen has been a standard regimen for ESCC, but it has been replaced by the CROSS regimen in the past few years, despite no prospective head-to-head comparative study has been performed.This is a single center retrospective study. Records of all ESCC patients who have received neoadjuvant PF with 40 Gy radiotherapy in 20 daily fractions (PFRT Group) or CROSS with 41.4 Gy radiotherapy in 23 daily fractions (CROSS Group) during the period 2002 to 2019 were retrieved. Propensity score matching (1:1) was performed to minimize baseline differences. The primary and secondary endpoints were overall survival and clinicopathological response. Subgroup analysis ("CROSS Eligibility") was performed based on tumor length, cT-stage, cM-stage, age, and performance status.One hundred (out of 109) patients (CROSS group) and propensity score matched 100 (out of 210) patients (PFRT group) were included. Esophagectomy rates in CROSS and PFRT group were 69% and 76%, respectively (P = 0.268). R0 resection rates were 85.5% and 81.6% (P = 0.525) and the pathological complete remission rates were 24.6% and 35.5% (P = 0.154). By intention-to-treat, the median survival was 16.7 and 32.7 months (P = 0.083). For "CROSS Eligible subgroup," the median survival of the CROSS and PFRT group was 21.6 versus 44.9 months (P = 0.093).There is no statistically difference in survival or clinicopathological outcome between both groups, but the trend favors PFRT. Prospective head-to-head comparison and novel strategies to improve the outcomes in resectable ESCC are warranted.

Cervical esophageal carcinoma (CEC) is rare, accounting for 2-10% of esophageal cancers and is mostly squamous cell carcinoma. Because of the anatomical proximity of CEC to larynx, surgical treatment would involve pharyngo-laryngo-esophagectomy (PLE) with inherent high mortality and morbidity. Laryngeal preservation is an important consideration, and definitive chemoradiotherapy is the recommended treatment. Treatment strategy of CEC can be more akin to treatment for head and neck cancers than to thoracic esophageal cancers. Since the exact location, extent of primary and nodal metastasis varies between patients, radiotherapy treatment needs to be individualized. The optimal radiation dose for CEC is uncertain, but retrospective data suggests that higher radiation dose of at least 60 Gy is associated with better local control and survival. Advanced radiotherapy technique, like intensity modulated radiotherapy, is usually required to achieve high dose to tumor while protecting normal tissues from excessive radiation.

With more understanding of the tumor biology, esophageal squamous cell carcinoma (ESCC) and adenocarcinoma are increasingly recognized as different disease entities and are managed with different treatment approaches. Most patients with ESCC need systemic treatment at some point of their disease course, but only until recently, the progress in systemic treatment has been relatively stagnant compared with its adenocarcinoma counterpart. Platinum-based regimens remain the standard of care, while taxanes have been increasingly used upfront and in later lines of treatment. The attempts to personalize treatment for ESCC with various target therapies have been futile. Immune checkpoint inhibitors are now coming into play with promising activity and potentials to combine with different treatment modalities. The current chapter overviews the systemic treatment for ESCC and highlights the recent development.

Esophageal squamous cell carcinoma (ESCC) is an aggressive disease. Many patients have locally advanced disease or already have distant metastasis at presentation. Radiotherapy plays an important role in the treatment of esophageal squamous cell carcinoma. Neoadjuvant chemoradiotherapy improves the survival and surgical outcome compared to surgery alone. Definitive radiotherapy (RT) with or without chemotherapy is used in patients who decline surgery or are medically inoperable. Palliative radiotherapy using external beam radiotherapy or intraluminal brachytherapy is effective for dysphagia and pain control.d.

With more understanding of the tumor biology, esophageal squamous cell carcinoma (ESCC) and adenocarcinoma are increasingly recognized as different disease entities and are managed with different treatment approaches. Most patients with ESCC need systemic treatment at some point of their disease course, but only until recently, the progress in systemic treatment has been relatively stagnant compared with its adenocarcinoma counterpart. Platinum-based regimens remain the standard of care, while taxanes have been increasingly used upfront and in later lines of treatment. The attempts to personalize treatment for ESCC with various target therapies have been futile. Immune checkpoint inhibitors are now coming into play with promising activity and potentials to combine with different treatment modalities. The current chapter overviews the systemic treatment for ESCC and highlights the recent development.

Esophageal squamous cell carcinoma (ESCC) is an aggressive disease. Many patients have locally advanced disease or already have distant metastasis at presentation. Radiotherapy plays an important role in the treatment of esophageal squamous cell carcinoma. Neoadjuvant chemoradiotherapy improves the survival and surgical outcome compared to surgery alone. Definitive radiotherapy (RT) with or without chemotherapy is used in patients who decline surgery or are medically inoperable. Palliative radiotherapy using external beam radiotherapy or intraluminal brachytherapy is effective for dysphagia and pain control.d.

Cervical esophageal carcinoma (CEC) is rare, accounting for 2-10% of esophageal cancers and is mostly squamous cell carcinoma. Because of the anatomical proximity of CEC to larynx, surgical treatment would involve pharyngo-laryngo-esophagectomy (PLE) with inherent high mortality and morbidity. Laryngeal preservation is an important consideration, and definitive chemoradiotherapy is the recommended treatment. Treatment strategy of CEC can be more akin to treatment for head and neck cancers than to thoracic esophageal cancers. Since the exact location, extent of primary and nodal metastasis varies between patients, radiotherapy treatment needs to be individualized. The optimal radiation dose for CEC is uncertain, but retrospective data suggests that higher radiation dose of at least 60 Gy is associated with better local control and survival. Advanced radiotherapy technique, like intensity modulated radiotherapy, is usually required to achieve high dose to tumor while protecting normal tissues from excessive radiation.

Background: Breast Cancer is the commonest female cancer worldwide and the most common female cancer in Hong Kong. Overseas studies have explored the knowledge and attitudes towards breast cancer, but most are targeted at general public. Similar studies were done among female health care personnel but mainly overseas with paucity of data within the Chinese community. This is a pilot study aiming at exploring the breast cancer prevention awareness and breast examination attitudes among Hong Kong women who work in a medical environment. Methods: This is a cross-sectional, qualitative pilot study targeting female nurses working at the Queen Mary Hospital, Hong Kong. We planned for 300 samples as pilot study to validate the questionnaire. This involved self-administrated questionnaires during 1st October 2013 to 30th November 2013. Altogether, 1800 questionnaires were distributed to nurses at Queen Mary Hospital through the Central Nursing Department. Results: A total of 317 completed self-administered questionnaires were collected. The age of the respondents ranged between 20-60, with the majority in the age group of 40-49 (28.4%), followed by 20-29 (27.4%). The mean years in practice was 17. Among the six diseases given for ranking (diabetes mellitus, breast cancer, hypertension, depression, cardiovascular disease, cerebrovascular disease), breast cancer is ranked as the most important disease for their age (37.2%). However, many respondents perceived the degree of risk of breast cancer during their life time to be average (34.1% with median score 5) or even lower (35% under median score 5). The knowledge towards breast cancer risk factor remained limited. Most of them did not identify late menopause (74.5%), advanced maternal age (70.6%) and young age at menarche (58.7%) as risk factors. For breast examinations, most respondents had performed breast self-examination (BSE) (91.2%), less than half of them performed BSE on a regular basis (only 39.4% performed BSE once every month). “The need of my age” (72.2%) and “I am more aware of breast cancer” (54.6%) are claimed to be the major factors encouraging them to perform BSE. Relatively few respondents had ever undergone clinical breast examination (CBE) (41.0%). Similar to the case of BSE, those who had undergone CBE are found to practise it irregularly (23.3%), comparing to 10.1% practising CBE once every year. More respondents with secondary educational level or above had mammography (p=0.000) or ultrasound (p=0.007) done than respondents with primary educational level or below which is statistically significant. Conclusion: The general breast cancer risk awareness among nurses in this pilot study is of concern. There is an unmet need to develop breast cancer preventive intervention program targeting at nurses. This pilot study helps to validate the proposed survey, and serves as the basis for our future design of appropriate intervention to enhance breast cancer awareness and improve early breast cancer prevention for female healthcare workers. Further study is warranted to be extend to female doctors, healthcare assistants and ward clerks etc. Citation Format: Janice Tsang, Siu Ting Yung, Alston Chiu, Henry Sze, Cindy Lai Shan Wong, Wendy Chan, Agnes Cheung, Eve Lai, Sin Ting Wong, To Wai Leung, Dora Kwong. Breast cancer prevention awareness and breast examination attitudes among Hong Kong women who work in a medical environment – A pilot study [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-11-15.

Background We aim at subdividing M1 stage to better predict survival of metastatic nasopharyngeal carcinoma (NPC) patients whose outcomes could vary greatly. Methods Patients with previously untreated metastatic NPC (training cohort) were recruited prospectively from 2007 to 2018 and were re-staged based on 8th edition of American Joint Committee on Cancer system. All patients had baseline plasma EBV DNA at diagnosis of metastasis. Characteristics of metastases (site, number and size of metastatic lesions) were confirmed by MRI and PET-CT. We used recursive partitioning analysis (RPA) incorporating baseline plasma EBV DNA and/or metastatic characteristics with internal validations to subdivide M1 stage. The two models were externally validated using an independent data set of 67 NPC patients who were non-metastatic at diagnosis but later developed distant metastases after radical treatment (validation cohort). Performance of survival prediction between the two models was compared with paired t-test under 1000 bootstrapping samples. Results The training cohort of 69 patients had a median follow-up of 40.8 months and 3-year overall survival (OS) of 36%. Model 1 incorporating pre-treatment plasma EBV DNA subdivided M1 stage into two groups: M1a (EBV DNA ≤2500 copies/ml; OS 74%) and M1b (EBV DNA >2500 copies/ml; OS 17%) (P 2500 copies/ml) (HR 4.7 (95% CI 1.9-11.5); P=.001) and metastatic site (coexisting liver and bone metastasis) (HR 2.2 (1.0-4.7); P=.046) were prognostic of OS. Model 1 demonstrated better model fit in predicting OS (Model 1: mean AIC 246.9 (95% CI 187.8-303.6) vs Model 2: mean AIC 257.7 (200.6-313.2); P Conclusions A novel RPA-based M1 stage set incorporating baseline plasma EBV DNA had a significantly better survival prediction, providing important values on prognosis and treatment decision making. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

OBJECTIVES Definitive concurrent chemoradiotherapy is the standard treatment for stage III non-small cell lung cancer (NSCLC). Previous studies showed that the tumor size and its metabolic activity are predictors of treatment outcome. We investigated whether there are new metabolic prognostic factors of survival for stage III NSCLC after definitive concurrent chemoradiotherapy. PATIENTS AND METHODS A total of 57 consecutive patients treated with definitive concurrent chemoradiotherapy for their stage IIIA (n=22) and stage IIIB (n=35) (AJCC 7th edition) unresectable NSCLC were identified. A total of 43 (75.4%) patients had positron emission tomography with integrated computed tomography (PET-CT) scan performed at diagnosis that were subsequently reviewed and analyzed. Prognosticators of progression-free survival (PFS), distant metastasis-free survival (DMFS), and overall survival (OS) were analyzed. RESULTS The median PFS, DMFS, and OS were 14.1, 12.6, and 37.8 months, respectively, after a median follow-up of 41.5 months. PFS advantage was demonstrated in stage IIIA versus stage IIIB (median 38.6 vs. 13.5 mo, P=0.020), N-stage N0-N2 versus N3 (median 16.7 vs. 8.1 mo, P

Malaria is widely associated with poverty, and a low-cost vaccine against malaria is highly desirable for implementing comprehensive vaccination programmes in developing countries. Production of malaria antigens in plants is a promising approach, but its development has been hindered by poor expression of the antigens in plant cells. In the present study, we targeted plant seeds as a low-cost vaccine production platform and successfully expressed the Plasmodium falciparum 42-kDa fragment of merozoite surface protein 1 (MSP1₄₂), a leading malaria vaccine candidate, at a high level in transgenic Arabidopsis seeds. We overcame hurdles of transcript and protein instabilities of MSP1₄₂ in plants by synthesizing a plant-optimized MSP1₄₂ cDNA and either targeting the recombinant protein to protein storage vacuoles or fusing it with a stable plant storage protein. An exceptional improvement in MSP1₄₂ expression, from an undetectable level to 5% of total extractable protein, was achieved with these combined strategies. Importantly, the plant-derived MSP1₄₂ maintains its natural antigenicity and can be recognized by immune sera from malaria-infected patients. Our results provide a strong basis for the development of a plant-based, low-cost malaria vaccine.