March 2022 SSO ONCOLOGY ARTICLE Dr Toh Han Chong The SARS (Severe Acute Respiratory Syndrome) Pandemic was scary – arriving on Singapore shores in March 2003 through index case EM returning from Hong Kong - an SQ stewardess who became known as patient 1 - a superspreader who while clinically stable infected over 130 cases. Tragically her father, mother and pastor who were in contact with her all died from SARS. A friend and colleague Dr Alex Chao passed from SARS and another friend since med school days was intubated in the Tan Tock Seng Hospital SARS intensive care unit (ICU) but thankfully survived. Over 40% of SARS cases were healthcare workers. I remember well then that at the National Cancer Centre Singapore (NCCS), we were all asked if we would step forward to volunteer for the oncology inpatient service at the Singapore General Hospital. No one stepped back, many making light of the moment with, “wait what ? Can only eat hospital food ah ?”. There was no food delivery apps then and we were not allowed to head out to favourite makan places like Tiong Bahru Market nor meet with anyone at the NCCS. Some tested their O2 saturation on the properly fitted N95 mask and it could drop below 80% making all a bit woozy at the end of a work day. All hospital scrubs went to a central hospital laundry daily. Follow up clinic visits were pushed back while active treatment cases continued to receive care. My cellphone then was a Nokia 8250 and text messaging was as far as good communications went. There was no phone camera to shoot and upload humble brag social media posts like, “check out my hot bod as I perform CPR like a boss !’ Oh no social media then. I’m kidding as almost all frontline healthcare workers work quietly, tirelessly, without fanfare. The bent double from kyphoscoliosis elderly Aunty Ou who just lost her husband some months back, who cleans our rooms, toilets and offices on the NCCS fourth floor so earnestly - is also that so invaluable workforce in the healthcare frontline. When I see the grit and fearlessness of colleagues during SARS and now throughout the Covid-19 pandemic, it is the same emotion I feel when I see cancer patients valiantly fight their cancer as their disease spreads and invades organs, and when everyday Ukrainians stand up to defend their homeland against military invasion and destruction. By June 2003, SARS disappeared, with 774 deaths and 8098 becoming sick from SARS globally. The Covid-19 pandemic has infected over 460 million with over 6 million deaths. This pandemic feels more like a festering chronic disease while SARS was a hard hitting acute shock. By 2003, we saw the birth and revolution of targeted cancer therapy with Imatinib achieving validated stunning responses and survival improvement in chronic myeloid leukaemia (CML). First generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors gefitinib and erlotinib showed powerful proof-of-principle effect against EGFR mutant non-small cell lung adenocarcinoma and later tailored at the phenotypic level in non-smoking Asian largely female patients as the landmark IPASS Phase III clinical trial led by the stylishly sharp sartorially tailored Tony Mok - a Hong Konger no less :D. In 2005, more good news arrived as HER2/neu targeting trastuzumab improved survival in combination with combination chemotherapy as adjuvant therapy in resected breast cancer. Ten years ago, cancer drug approvals numbered less than 10 drugs a year to now an average of one new drug approval a week. This means that drug permutations, combinations, sequencing and algorithms are now so much more complex. Cancer patients can potentially live much longer many with good quality lives including remarkable supersurvivors especially on immunotherapy. But this also sets up a perfect storm of soaring cancer drug costs. The 2018 China film ‘Dying to Survive 我不是药神 ’ both funny and moving, about an ah beng aphrodisiac seller and his friends bringing in an India generic version of ‘Glinic’ to save CML patients as the original Glinic sold by a Western pharma is priced too high beyond the reach of many China CML patients. This film caught the attention of China Premier Li Keqiang and the Chinese Government moved to cut cancer drug pricing. For the senior oncology residents swotting for their medical oncology board exams, there is now so much more to remember. Yet for must-know cancers such as germ cell tumour, anal canal cancer, small cell lung cancer and lymphoma, the chemotherapy backbone has remained surprisingly constant with some added immunotherapy to boot in small cell lung cancer and lymphoma. For chemotherapy of gastrointestinal cancers then, if the candidate said ‘5 FU’, one could likely still pass LOL. Adjuvant FOLFOX for resected colorectal cancer was published in The New England Journal of Medicine in 2004. As a senior resident, I was prescribing one year of adjuvant 5FU based chemotherapy then later down to 6 months and now 3 months in lower risk resected colorectal cancer, where decision to treat may be driven by an immune microenvironment biomarker, the Immunoscore. The immune microenvironment was once pooh poohed as an irrelevant Cinderella bystander. Speaking of pooh, the modulation of the gut microbiome looks to improve outcomes to immune checkpoint inhibitors and now CAR T cell therapy. Truly you are what you eat to prevent cancer and to improve cancer outcomes. The 90’s oncology mantra embraced mega doses of bigger is better chemotherapy, to more is better, to the now more science-driven more precise therapies - a new vista of oncology. Today, single cells can be examined closely, exact protein folding and cancer diagnoses can be solved by Artificial Intelligence, and drugging the undruggable is no longer a fantasy. Immunotherapy rocks on as next generation immune checkpoint inhibitors such as anti-LAG-3 relatlimab hits prime time, improving survival over nivolumab alone in melanoma patients. In this current Covid-19 pandemic, Singapore and our healthcare system have been much more prepared. A big shout out to our Government for successfully driving the national vaccination programme making Singapore one of the most vaccinated countries in the world. There was no SARS vaccine then but cutting edge cancer research technology now including by Ugur Sahin and wife Ozlem Tureci founders of BioNTech has led to the supersonic speed development and delivery of the Covid-19 vaccines – a crowning triumph of all of science, technology, academia, industry, non-government organisations and governments. As much as we could support, it was business as usual in particular for the in-need patients but yes rules such as limited visitation by family and friends to the hospital wards made it hard for many cancer inpatients. This year in Singapore we lost a giant – the indomitable Cynthia Goh – to pancreatic cancer. Cynthia was a pioneer and leader of palliative medicine not just in Singapore but also the region. Years ago while visiting a cancer institute in Dhaka, Bangladesh, the senior staff asked me if I knew Cynthia Goh. They conveyed that Professor Goh had done so much to help and build palliative care services and train their staff. Similar testimonies rang across many South-east Asian countries as tributes poured in following her passing. I felt so proud to hear that and so privileged to be her colleague. Another colleague who gives me so much inspiration, as do so many others, is my NCCS clinic staff nurse who lives with cancer and has been on and off and on treatment. Walking in their shoes, she has inspired and given strength to so many cancer patients. I also learnt that she took care of the final rites and ceremony of a young lonely cancer patient who had no friends nor family after her battle with terminal cancer finally ended. This staff nurse’s favourite refrain to our patients all these years has been, ‘Its OK, you’ll be OK.’ Surely Nightbirde who battled breast cancer and passed on the same week as Cynthia Goh would also want us to always remember, ‘Its OK !’