5th Hong Kong Innovative Core Developments in Precision Oncology of Greater Bay Areas

The 5th Hong Kong International Oncology Symposium (5th HKIOS) was conducted in Hong Kong Science and Technology Park and City University of Hong Kong on Nov 10 & 11, 2018 respectively. The event this year was joined by renowned speakers with a higher representation from the Guangdong-Hong Kong-Macau Greater Bay area to reflect our important initiative of developing research and medical care collaborations in this heavily populated region.

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Day 1 : ClubONE, G/F, W12 – Hong Kong Science and Technology Park

Day 2 : Senate Room, 19/F, Lau Ming Wai Academic Building – City University of Hong Kong

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Speakers:
    Speakers:

      Dennis LO
      Circulating DNA in plasma is an active researched area for the development of liquid biopsies for cancer. My group has been particularly interested in the use of Epstein-Barr virus (EBV DNA) in plasma for the detection of nasopharyngeal carcinoma (NPC). We have completed a screening study involving over 20,000 subjects. We have observed the ability of circulating DNA to detect NPC than is otherwise possible. These results and their clinical implications will be discussed in this talk.

      Tim Hui-Ming HUANG
      Recent advances in single-cell omics enable us to study the dynamics of oncogenic ecosystem. We used this approach to determine how tumor cells evolve from in situ proliferation to distant colonization through blood circulation. A combined single-cell genomic and transcriptomic analysis of diverse tumor cell subpopulations identified active signaling pathways that are crucial for disseminated cells to withstand hemodynamic stress of blood flow. Compared to primary tumor cells that preferentially use glycolysis for Warburg metabolism, circulating tumor cells (CTCs) were compelled to exploit oxidative phosphorylation (OXPHOS) for alternative fuels. This metabolic rewiring appears to be a survival strategy to provide energy needed for mobility and migration of CTCs. In contrast to the notion that these cells undergo mesenchymal-to-epithelial transition, we found that CTCs have biphenotypic features with both epithelial (i.e., more adhesive) and mesenchymal (i.e., more elastic) traits. The hybrid characteristics greatly enhance their durability to tether to companion cells that support intercellular transfer of biomolecules to CTCs in unfavorable microenvironments. This finding, which is not evident through molecular analysis of bulk tumors, provides a window of therapeutic opportunity to target metabolic vulnerabilities of tumor cells when they enter the bloodstream.

      Edwin Chong-Wing CHEUNG
      The transmission of extracellular signals into intracellular responses is a fundamentally important process in biology. Lipophilic hormones such as steroid hormones are small molecules that function in signal transduction during growth and development. Aberration in the signaling pathways controlled by these hormones lead to disease states. We are interested in understanding the underlying mechanisms of nuclear hormone signaling and how they relate to diseases such as cancer. Specifically, we are examining how steroid hormones such as estrogens regulate the transcriptional activities of their cognate receptors. Using a combination of molecular and cellular techniques, as well as genomic and bioinformatic approaches, we have examined the global binding sites (cistrome), chromatin interactions (interactome), and transcripts (transcriptome) at the single-cell level by the estrogen receptor and their coregulators. Overall, our analyses revealed that 1) spatial organization is an important and widespread mechanism used in nuclear hormone signaling, 2) collaborative factors are essential molecular determinants in estrogen receptor-mediated chromatin transcription, and 3) hormone signaling elicits a highly heterogenous transcriptional response.

      Michael Meng-Su YANG
      Using single cell transcriptional analysis of EMT-related genes, we investigated the heterogeneities of isolated cells in 192 disseminated single cells (DSCs) and 195 intra-cluster single cells from 27 disseminated tumor cell clusters (DTCCs) from malignant ascites of epithelial ovarian cancer (EOC). A stromal cell subpopulation was recognized through unsupervised classification of DSCs based on their distinct gene expression levels. The extracted stromal-specific gene signature (SNAI1, BRCA1 and IGFBP4) showed significant predictive power in identifying high-risk EOC patients. For DTCCs, the intra-cluster single cells were classified into putative subpopulations based on the characterized DSCs, where the intra-DTCC tumor cells showed more mesenchymal traits as well as self-protection features than the disseminated single tumor cells. The intra-cluster heterogeneity of DTCCs revealed the role of stromal cells in upregulated EMT signals associated with the aggressiveness of DTCCs.

      Speakers:

        Cassian YEE
        Adoptive Cell Therapy (ACT) has enjoyed a revival in recent years for hematologic malignanices but advancing its use for the treatment of solid tumors will require addressing cell intrinsic as well as tumor micro environmental hurdles and exploiting a broader ACT platform that includes not only engineered CAR-T cells, but also other forms of ACT including Endogenous T Cell (ETC) Therapy Endogenous T cell therapy utilizes specialized methods to isolate and expand from peripheral blood, tumor-reactive T cells, often present at very low frequency, and, by sourcing effectors from the entire TCR repertoire, provide the greatest flexibility in delivering a T cell product of defined specificity and phenotype. Several first-in-human studies performed by our lab demonstrate the importance of antigen spreading in generating long-lasting clinical responses as well as identifying T cells with memory properties. The ETC therapy approach allows for the greatest flexibility in targeting personalized and shared antigens and rapid implementation of adoptive cell therapy from epitope identification to T cell infusion. To broaden the pool of patients and extend the use of adoptive cell therapy to several solid tumor malignancies such as ovarian, lung, GI and breast cancers, we have validated several high value target tumor antigens that are expressed in significant fraction of these tumors which are now being evaluated in combination clinical trials.

        Frank FAN
        Over the past several years, CAR-T cell immunotherapy has emerged as the most promising celltherapy in treating cancers. Funded by GenScript, Dr. Fan founded Legend Biotech in 2014 and built an elite R&D team exploring innovative cell therapy. In just 3 years, the company grew from a freshstart to a global leader in the CAR-T cell therapy. Legend Biotech has successfully developed a proprietary multi-specific CAR-T platform which differentiate the company from all other CAR-T companies in the world. The innovative CAR-T technology platform applied Camelid single domain antibody as antigen binding domain for the CAR design and it demonstrated significant clinical benefit in terms of safety and efficacy. Multiple Myeloma had been largely considered an incurable cancer in the field of hematologic malignancy. Dr Fan’s group not only proved that BCMA molecule is one of the best CAR-T target for treating multiple myeloma, but also designed an innovative bi-epitope targeting CAR-T modality in which myeloma cell surface BCMA molecule will be captured by the CAR-T cells at two different epitopes simultaneously, thus effectively prevent the cancer cell from escape. The LCAR-B38M CAR-T cells had been proven to be the best-in-class therapy for multiple myeloma via an investigator initiated clinical trial conducted in China. 74 relapsed or refractory multiple myeloma patients had been treated in the trial and the ORR has been reached as high as 95%. Most patients experienced a deep and durable clinical remission after the cell infusion. The innovative product became the first cell therapy product obtained the first ever IND approval for CAR-T cell product from the Chinese FDA. Legend Biotech now form a global partnership with Janssen to co-develop the world market of the product.

        Shu-Jen CHEN
        The success of immune checkpoint inhibitors in a subset of cancer patients has led to major efforts in identifying predictive biomarkers. In addition to PD-L1 staining and microsatellite instability, factors such as tumor mutation burden, antigen presenting machinery and immune resistance signals, should also be considered when evaluating a patient for immunotherapy. Next generation sequencing (NGS) technology allows the profiling of hundreds and thousands of genes using limited amount of tumor tissue. NGS has gradually being adopted in clinical diagnostic setting to detect complex biomarker. In this talk, example of using NGS-based profiling to predict response to immune checkpoint inhibitor will be discussed.

        Lei ZHENG
        Immune checkpoint inhibitors have made the breakthroughs in treating systemic diseases of many types of malignancy. However, only approximately 20-30% of all cancer patients are sensitive to immune checkpoint inhibitors. Multiple combinations of Immunotherapy are being tested, but yield little success. Lack of rational combination is the main reason of the failure in developing the combination Immunotherapy. To develop rational combination immunotherapy, a comprehensive analysis of the tumor microenvironment is necessary and would identify the exact deficiencies that would needed to be targeted by multiple types of Immunotherapy. In addition, the rational combination of Immunotherapy should be validated in the preclinical models that resemble the tumor microenvironment. Finally, prior treatments such as chemotherapy and radiation that the patients have received may have reprogrammed the tumor microenvironment that may reset the sensitivity and resistance to the combination Immunotherapy. Therefore, the development of combination Immunotherapy should also consider and even take advantage of the reprogrammed tumor microenvironment that may sensitize the tumors to a particular combination of Immunotherapy.

        Speakers:

          Patrick PADDISON
          Glioblastoma (GBM) is the most aggressive and common form of adult brain cancer and is among the deadliest cancers, with a median survival of 15 months using standard-of-care therapies. Thus, improved treatments for GBM are desperately needed. To identify new GBM molecular therapeutic targets, our group has performed multiple functional genetic screens in patient-derived GBM stem-like cells (GSCs) and non-transformed human neural stem and progenitor cells, which represent non-neoplastic controls. These screens, which have used both RNAi and CRISPR-Cas9 platforms, have led to the identification of several key molecular vulnerabilities in GSCs, including GBM-specific defects in: 3' splice site recognition, kinetochore function, and loss of redundancy between the kinase activities of PKMYT1 and WEE1. At this meeting, I will summarize our work in this space as well as detail some new directions in lab in defining quiescence-like states for GBM.

          Chu-Xia DENG
          Cancer is the leading cause of human death. There are 18 million new cancer cases and 9.6 million cancer related death worldwide in 2018. As the process of aging population acceler- ates, the incidence and death rate will further increase. With an average life expectancy of 85 years, Macao is the second longest living region in the world. It is also one of the regions with high incidence of cancer and high mortality. For example, cancer mortality accounts for 35-37% of total mortality in 2012-2017, which is the highest in the world. However, the current research on cancer in Macau is relatively weak. Thus, we will conduct comprehensive and in-depth research on several major cancers in Macau to facilitate precision oncology to identify cancer-driven mutations, and conduct in-depth understanding of the major types, incidence, molecular characteristics, and cancer-driven mutations of these cancers.

          We have now established a variety of technologies such as DNA sequencing, gene transcriptomics, proteomics, epigenetics, metabolomics, bioinformatics analysis, and in vivo and in vitro model experimental platforms. We conducted genomics and drug susceptibility tests on some tumors in order to identify targeted high-effective drugs for these cancers. The information obtained will be handed over to doctors in partner hospitals to assist them in formulating tailor-made personalized treatment plans. Our long-term goal is to establish an effective anti-cancer treatment system through cooperation with Macao and its neighboring hospitals, and to contribute to the extension of the healthy life of the people of Macau and nearly areas.

          Xiao-Tian ZHANG
          About 10% gastric cancer patients have familial cancer history, patients diagnosed of Hereditary Diffuse Gastric Cancer (HDGC) account for 1%-3%. HDGC is an autosomal dominant disease with pathological types of diffuse and/or signet ring cell. Foreign researches reported that germline mutations was found in about 40%-50% HDGC family pedigree and there is a definite correlation between CDH1 mutations and HDGC. For CHD1 mutations carriers, lifetime risk of developing GC is 80% while patients with lately-stage diffuse GC have an extremely poor prognosis. Prophylactic gastrectomy and radical gastrectomy are the standard treatment for CHD1 carriers and early-stage HDGC patients respectively. However, due to the non-specific symptoms, most patients were found in advanced stage. Hence, the screen of HDGC familial pedigree is significant. Whereas there are few researches about HDGC in China caused by doctors’ lack of awareness and the lack of CHD1 detection center. This review will elaborate the current status and prospects of HDGC, current situations and challenges of HDGC in China will also be involved.

          Ava KWONG
          Mutations due to hereditary related genes such as BRCA1, BRCA2, TP53, PTEN and PALB2 confer greater risk of developing breast cancer and for BRCA mutations, and where relevant, also ovarian cancer. The risk assessment based on genetic testing allows options of high risk surveillance, prevention and may now also guide use of specific therapies for treatment such as targeted therapies and use of platinum base chemotherapy. There are known ethnic variations in mutation types, prevalence. The choice of management, once an individual has been found to carry the BRCA mutation may also vary. Moreover the availability of genetic testing, method of testing such as the transition into the use of Next Generation Sequencing techniques may also vary in different parts of the world and still have some limitations in some Areas in Asia.

          The Hong Kong Hereditary Breast Cancer Family Registry was establishment in 2007. High risk women based on their age and family history were recruited from both public and private hospitals and clinics of Hong Kong since March 2007. Medical information was prospectively collected from the patients and medical records. Epidemiological surveys, choice of management questionnaires were received from each individual.

          Local data of the Hong Kong Hereditary Breast Cancer Registry and its collaborative work with University of Hong Kong will be shared.

          Speakers:

            Yun YEN
            Precision medicine has started to deliver positive improvements on health care delivery, patient care, drug discovery, and preventive interventions. Notably, the incorporation of genomic, proteomic, pharmacogenomic, molecular, and patient lifestyle data into clinical medicine promises to improve our ability tailor medical treatment according to the individual characteristics of each patient. Artificial intelligence (AI), or the use of computer algorithms to analyze, learn from, and predict outcomes from medical data, has become an emerging tool to help physicians and scientists translate big data to better patient outcomes and targeted care. However, despite these promising opportunities for healthcare, AI also raises ethical, legal and policy challenges for all stakeholders of the healthcare ecosystem. In particular, the prospect of using AI in our current Precision Medicine era requires careful and continuous evaluation of how professionals, providers, organizations, and industries integrate machine learning with clinical practice, data sharing, medical education, and health systems. We explore several avenues where AI can advance medical diagnosis, performance, and discovery as well as examine the major challenges that AI brings with its implementation in science and health care.

            Zhi John LU
            I will introduce and present our bioinformatics software package: ncRNA Project. It includes RNAfinder, RNAstructurome and RNAtarget. We have applied them to many biological and medical (i.e., cancer) applications.

            Based on genomics and bioinformatics, we identify novel extra-cellular RNA (exRNA) biomarkers in bio-fluids associated with tumorigenesis and cancer development, using machine learning approaches and high-throughput sequencing technologies. exRNA includes many types, such as miRNA, Y RNA,circRNA,lncRNA, etc. The identified exRNA biomarkers will be applied to early diagnosis and prognosis in China’s top lethal cancers, including lung adenocarcinoma, stomach adenocarcinoma, liver hepatocellular carcinoma, esophageal carcinoma and colon adenocarcinoma, etc.

            Subsequently, we will set up a standard operating procedure (SOP) and bioinformatics method for exRNA biomarkers of cancer, from sample collection, sequencing protocol, validation method to analysis software. The application will be an accurate, reproducible and robust method for cancer diagnosis and/or prognosis.

            Wen-Tao WU
            The diagnosis and therapy of tumor rely on imaging, including Imaging Guided Diagnosis / Operation / 3D Printing / Education (IGDOPE). Artificial intelligent will improve efficiency and quality of imaging processing, so it will improve diagnosis / operation / 3D printing / education. For quality control, standard protocols of imaging scan are defined as imaging guidance separately for each tumor (central Nervous system tumor, bone and joint tumor, liver cancer, pancreatic cancer, Lung cancer), For the diagnosis, the lung-RADS evaluation is made by the AI assisted screening and analysis of lung nodules in chest CT, which is helpful for clinicians to decide observing or surgery. For the surgical planning, multi-modality imaging fusion and registration, and segmentation are assisted by AI, so the relationship among 3D models of structures can be revealed precisely to surgeons. During surgery, surgical guide plates are designed based on imaging-guided surgical planning, and they are 3D printed and used in surgery to precisely improve the operation and shorten the time. Based on experience of imaging-guided surgery on the clinical cases, it can be used for training resident doctor as case-based learning curriculum by VR techniques.

            Speakers:
              Speakers:

                Jie HE
                • Cancer incidence and mortality in China
                • Cancer trends in China
                • Cancer survival in China
                • National Cancer Control Framework

                Speakers:

                  Jie HE
                  • Cancer incidence and mortality in China
                  • Cancer trends in China
                  • Cancer survival in China
                  • National Cancer Control Framework

                  Speakers:

                    Polly CHEUNG
                    Breast Cancer has been the number 1 cancer affecting women in Hong Kong since 1994. The number of new cases has risen from less than 1000 to more than 4000 cases in the last two decades. The life time risk of women in Hong Kong is now 1 in 15.

                    Primary prevention measures include promotion of breast cancer awareness, modification of dietary and life style factors. Secondary prevention measures include regular breast screening by mammography with or without addition of ultrasound.

                    The current status and practice of primary prevention and secondary prevention measures will be discussed.

                    Shelly Lap-Ah TSE
                    Cancer is the leading cause of morbidity and mortality in China. Emerging environmental exposures induced by rapid industrialization and westernization have contributed to the sharp increases in cancer incidence in China, and challenges are particularly critical in Greater Bay Area of China. The aim of this report is to compare the time trends of cancer incidence in Hong Kong, Guangdong and Macau to understand the etiology implication behind. Also, results of age-period-cohort analysis using dataset of Hong Kong and other areas are also presented to raise hypothesis of potential environmental risk factors in the etiology of selected cancers (lung cancer, breast cancer, nasopharyngeal cancer, thyroid cancer, and oropharyngeal and oral cavity cancers). Finally, major research outputs in cancer epidemiology conducted by the research team for lung cancer, breast cancer and prostate cancer will be shared, particularly in the field of indoor air pollution and lung cancer, shiftwork/circadian rhythm and breast cancer, and bisphenol A and other environmental risk factors and prostate cancer. Interdisciplinary collaboration amongst clinical, environmental public health and policy people between Hong Kong, Guangdong and other areas of mainland China is desired to deal with the increasing burden of cancer and safeguard the population by better prevention and control.

                    Jie HE
                    • Cancer incidence and mortality in China
                    • Cancer trends in China
                    • Cancer survival in China
                    • National Cancer Control Framework

                    Speakers:

                      Ju-Wei MU
                      Early stage lung cancer has emerged as a major concern to thoracic surgeons in recent years. Several new techniques have been used in the biopsy and localization of small lung lesions, while the efficacies were still unsatisfactory. We compared several main location techniques and initiated our experience- He’s marker. He’s marker was a combined technique based on lungpoint or lungpro system to navigate the airway path led to the nodule under the direct vision of endoscopy. The main core of marker was a superelastic nitinol that can be ejected by a launcher whenever reached the location targeted by the navigation system. The localization was extremely accurate and able to be used for further purpose of treatment. On the other hand, segmentectomy has been adopted as a main treatment for early stage lung cancer, especially GGO. But the surgical technique of segmentectomy still had some defects. So we’d like to introduce our own experience- anatomical partial lobectomy which was able to guarantee the surgical margin strictly conforming to the principles of oncology treatment and could be mastered by most of the surgeons in a relatively short time. We will discuss the details of these techniques and introduce Shenzhen hospital at the present.

                      Gui-Bin QIAO
                      The majority of non-small cell lung cancer (NSCLC) patients are first diagnosed with advanced stage disease. The prognosis of advanced NSCLC is poor and survival is measured in months. Standard therapeutic treatment regimens for patients with stage IV NSCLC typically include chemotherapy and palliative radiation. Despite newer regimens that may include molecularly targeted therapy and immunotherapy, the overall 5-year survival for stage IV disease is not optimistic. Although therapeutic surgery is performed in a minority of cases, accumulating data suggest that thoracic surgery may play several beneficial roles for these patients. A lot of data suggest that for carefully selected patients with advanced stage NSCLC, surgical intervention can be an important component of combined modality treatment.

                      Alan SIHOE
                      Over the last 2 years, we appear to have become accustomed to ‘fake news’ ‘and alternative facts’ being all around us.

                      In recent times, Thoracic Surgery has witnessed a renaissance in technique and technology. ‘Next generation’ minimally invasive surgical approaches have arrived – including Needlescopic, Uniportal and Subxiphoid approaches to the chest and ‘non-intubated’ anesthesia. In technology, new and innovative robotic platforms, surgical instruments and video technologies promise to further improve patient outcomes after operations in the chest.

                      But could these all be ‘fake news’?

                      The promises of these marvelous ‘advances’ have often not been supported by hard clinical evidence. Worryingly, these new surgical attractions may be distracting from the areas most needing real development - such as enhanced post-operative recovery programs and research into the peri-operative patho-physiological environment.

                      This short talk explores the hype in thoracic surgery, and asks whether surgical advances need to be held to a higher standard.

                      Speakers:

                        Hon-Chi SUEN
                        The trachea and esophagus share a common blood supply from a longitudinal artery along the tracheoesophageal groove on each side. Esophagectomy, especially with lymph node dissection, compromises the blood supply to the trachea and carina resulting in ischemia at the airway anastomosis after concomitant airway resection predisposing to failure. As a result, combined esophagectomy and circumferential tracheal or carinal resection has been reported only sporadically. Carinal pneumonectomy (pneumonectomy together with resection of carina followed by anastomosis of the contralateral main bronchus to the trachea) is considered one of the most challenging thoracic surgeries by itself. Successful combined esophagectomy and carinal pneumonectomy has never been reported before.

                        A 59-year-old man was found to have a mid-esophageal cancer with local lymph node involvement resulting in left recurrent nerve paralysis. He was treated with chemotherapy and radiation, but the cancer continued its aggressive course invading the distal trachea and left main bronchus resulting in hemoptysis imminently threatening his life with massive hemoptysis. The patient sincerely requested aggressive surgery to palliate his condition and to prevent death from massive hemoptysis. After extensive consideration, it was determined that combined esophagectomy and left carinal pneumonectomy was the only option available. The patient was extensively counselled regarding the fact that the proposed procedure has never been successfully performed before and was extremely high risk, but he was very determined to undergo it. A 10-hour operation was successfully performed. He enjoyed meaningful palliation at home and gained ten more months of useful time to spend with his family.

                        Hai-Yu ZHOU
                        Dealing with small pulmonary nodule, to achieve an personalized, precision medicine therapy is the emphasis of full process management of early stage lung cancer. The consistent update of lung cancer screening guideline including NCCN or Fleischner Society indicate the tendency of lightening radiation and financial burden of patients. The follow-up strategy of small pulmonary nodule still depends on the risk factors and nodule size, however, when talking about GGO (Ground-glass opacity) ,some important quantitative characteristics including CTR (maximum diameter of consolidation relative to the maximum tumor diameter) has not received enough attention in guideline. So, it’s no doubt that the radiomics may play an important role in the early precise diagnosis of lung cancer. The standard surgery for small pulmonary nodule is pulmonary lobectomy and systematic mediastinal lymphadenectomy, but the sublobectomy is being focused gradually because it retains more lung tissue and pulmonary function. We are looking forward several large scale clinical trials (JCOG0804/JCOG0802/JCOG1211) to show whether sublobectomy can achieve non-inferiority outcome compared with lobectomy in small pulmonary nodule patient. What’s more, with the development of medical technology ,the precise localization of small pulmonary nodule will be auxiliary to diagnosis or surgery .Precise management of small pulmonary nodule needs multi-discipline cooperation to provide with comprehensive and objective decision and has the possibility to translate it into chronic illness.

                        Victor Ho-Fun LEE
                        Apart from the most common EGFR mutation in non-small cell lung cancer, other relatively less common mutations including ALK, ROS1, BRAF and MET has caught recent attention since these mutations are gradually becoming actionable and targetable with effective tyrosine kinase inhibitors.

                        Not only we should know about the mechanisms of actions, efficacy and safety of these targeted therapy for these rare mutation-driven lung cancers, we should also be very vigilant about the acquired drug-resistant mutations which develop after failure to these agents so that we can better decide the most appropriate subsequent therapies based on the resistance patterns emerging from the tumours.

                        In this lecture, the most updated recent advances of targeted therapy for ALK, ROS-1, BRAF and MET rearranged, mutant or amplified metastatic stage IV non-small-cell lung cancer will be discussed. Future treatment strategies to tackle progressive disease after failure to targeted therapy will also be shared.

                        Speakers:

                          Yan-Hong GU
                          The characteristics of the Chinese Society of Clinical Oncology (CSCO) guideline for colorectal cancer diagnosis and treatment are as follows: On the one hand, not only does it have considered the vast territory and uneven development of China, but it also makes recommendations in the light of the accessibility of medical resources and treatments as well as the grade of evidence category. On the other hand, the CSCO guideline is more legible and accessible than other foreign guidelines, such as NCCN and ESMO guidelines. The European associated guidelines and the National Health Commission's criterion for colorectal cancer treatment with too much narration have not readability. In contrast, the CSCO guideline shows in the form of concise tables with patients’ stratification of clinical manifestations, making it convenient to find the corresponding treatment strategies. In conclusion, the CSCO guideline for colorec- tal cancer diagnosis and treatment is concise, practical and down-to-earth.

                          Ka-On LAM
                          Cancer is a global health threat and colorectal cancer is now the No.1 cancer in Hong Kong, surpassing lung cancer since 2014. Although surgery with or without adjuvant therapy cure early disease, still a large number of patients either present with or recur with distant metastasis. Except those patients with resectable metastasis and thus a more favorable prognosis, most of the patient with metastatic disease succumb to the disease despite lines of systemic therapy. Refractory colorectal cancer traditionally refers to cancer that have failed fluoropyrimidine, oxaliplatin, irinotecan, anti-VEGF and anti-EGFR therapy. However, advances in treatment options and management strategies have brought new hope to patients. New agents like regorafenib and TAS102 have proven efficacy in various phase III randomized controlled trials. Immune check point inhibitor represents a new standard of care in patients with MSI-H tumor. Last but not least rechallenge strategy especially with guidance by liquid biopsy or target therapy with genomic guidance are both promising. The current presentation will highlight the current situation in refractory colorectal cancer and discuss emerging treatment strategies.

                          Xiao-Feng CHEN
                          Targeting angiogenesis in gastrointestinal tumors: current challenges and future directions.

                          The approval of anti-angiogenic therapy has led to an increase in the rate of overall survival (OS) of patients with advanced colon cancer. The drawback of the anti-angiogenic therapy is that their effect is short-lived and many patients progress through these therapies. Various mechanisms of resistance have been hypothesized, but overcoming this has been challenging. Also, there are no standardized predictive biomarkers that could aid in selecting patients who responds to the therapy upfront. We will discuss these challenges and take a look for the future directions.

                          Speakers:

                            Tony WONG
                            The use of pencil beam scanning (PBS) has revolutionized proton beam therapy. With the clinical use of Monte Carlo (MC) dose calculation and aperture-collimated proton beams, we can further improve the quality of proton treatment plans. This study aimed to validate our clinical treatment planning system’s (TPS) MC calculation of the lateral penumbra of brass-aperture-collimated PBS beams. We accomplished these aims by optimizing PBS beams using various combinations of planning parameters such as air gap and range shifter thickness at multiple depths in a homogenous geometry and validating the TPS-calculated penumbra values against film measurements.

                            Beam specific target volumes were generated using the RaySearch RayStationTM (v6.0) TPS. Collimated and non-collimated PBS fields were optimized on these targets for range shifters of different thicknesses (0cm (RS0), 4.0cm (RS40), and 7.5cm (RS75)) and air gaps (5-30cm) using MC dose calculation. Lateral penumbra (80/20) was measured at 2cm intervals across each target volume to characterize penumbra variation with depth for each range shifter thickness. Next, penumbra was measured at four depths (7cm, 11cm, 15cm and 19cm) for each variation of distance between range shifter and phantom surface to characterize the dependence of lateral penumbra on airgap.

                            Analysis of the variation of penumbra with airgap shows that reduction is largest at shallow depths and small air gaps. Film measurements of penumbra agree with TPS-calculated values within +/- 1mm. Results indicate that the use of apertures for PBS treatments is most beneficial for shallow targets while minimizing airgap.

                            Roy MA
                            With the recent technologic advancements in precision radiotherapy, Stereotactic Body Radiation Therapy (SBRT) has become an efficacious and safe treatment option for both primary and secondary liver cancers.

                            SBRT treatment for liver cancer patients at the BC Cancer Agency, Vancouver Center started in 2010. An overview of the Vancouver SBRT technique for liver tumors is presented, with a special focus on the evolution in the clinical implementation of sophisticated motion management techniques such as Respiratory Gating in 2013 and Dynamic Tracking in 2017.

                            The BC Cancer Agency, Vancouver Center experience of SBRT for both hepatocellular carcinomas (HCC), and small (up to 5 cm) liver metastases are reviewed, highlighting the differential response and toxicity to radiation between patients with HCC and liver metastases. Lastly, some potential strategies for future research will be discussed.

                            Jonn WU
                            Precision radiotherapy in head and neck cancers can be improved with different techniques, including immobilization, target and organ localization and conformal radiotherapy planning. We will review strategies currently used and in development at the BC Cancer Agency to improve the efficacy and decrease radiotherapy toxicity for our head and neck patients.

                            Mitchell LIU
                            Stereotactic body radiation therapy (SBRT) also referred to as stereotactic ablative radiotherapy (SABR), is a technique which has emerged over the past two decades due to improvements in radiation technology. Unlike conventional external beam radiotherapy (cEBRT) which traditionally delivers radiation in small doses [approximately 2 Gray (Gy) per fraction] over several weeks, SBRT, typically delivered in one to eight fractions, is a technique whereby potentially ablative doses of radiotherapy (usually 7.5–20 Gy per fraction) can be delivered with steeper dose gradients and sub millimetre precision, minimising risk to surrounding normal tissues. The potential benefits of excellent tumor control with low toxicity has led to the increasing use of SBRT in a number of clinical situations. Due to compelling evidence, SBRT is now the treatment of choice for medically inoperable patients with peripherally located stage I non-small cell lung cancer (NSCLC). The evidence base supporting the use of SBRT as a novel treatment for spinal metastases and oligometastases is rapidly expanding but challenges remain in these difficult patient populations. In an era where targeted therapy and improved systemic treatments for stage IV cancer have resulted in increased disease-free survival, and our knowledge of the oligometastatic state is ever expanding, using SBRT to treat metastatic disease and gain durable local control is increasingly desirable. Several randomized trials are currently underway and are sure to provide valuable information on the benefit and utility of SBRT across many tumor sites including early-stage NSCLC, spinal metastases and oligometastatic disease. Recognizing the evolving role of SBRT in clinical practice, this presentation will provide a review of recent developments in each of these areas.

                            Tai-Chung LAM
                            Stereotactic body radiation therapy (SBRT) is the new development of radiation oncology which aims to increase the tumor control efficacy by employing ablative radiation dose to tumor. Such high radiation dose was impossible in conventional radiotherapy setting, and is now made possible by SBRT, as SBRT is able to deliver anatomically accurate, highly conformal radiation beam to target volume, while avoiding radiation-sensitive normal tissue. SBRT is also possible for mobile tumor by accurate tracking of tumour motion before and during radiotherapy treatment.

                            The advantages of SBRT, including superior local tumor control, favourable toxicity profile, logistic convenience and easy integration with systemic cancer treatment schedule, are recognized worldwide. In fact SBRT has gradually emerged as an effective and preferred treatment options for various indications including early lung cancer, liver cancer, renal tumor, spinal metastases and radical treatment for oligometastasis.

                            In Hong Kong, SBRT has been introduced in public and private hospitals in the past decade. Yet, the pattern of SBRT application was markedly heterogeneous. Thus there was an unmet need to improve the service provision of SBRT to cancer patients in Hong Kong. In view of this, we have established a territory-wide collaborative platform, the HK-SBRT-study group (HKSBRTSG) to promote the education, knowledge exchange and clinical research of SBRT and hence to improve the service standard of SBRT in Hong Kong. In the talk, the local experience of SBRT will be summarized and we will also outline the future strategic development of HKSBRTSG.

                            Speakers:
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