WE would like to thank Gan Tee Jin for the letter “Keeping an open mind on unproven treatments” (The Star, March 10). We appreciate the effort to describe his family’s experience with HITV (Hasumi Immuno-Therapeutic Vaccine) and are glad that his mother has had a successful outcome after her treatment.
His mother is a living testimony that cancer is not always a death sentence, which sadly is an all too common perception among Malaysians.
We welcome feedback to our previous letter, “Clarifying immunotherapy” (The Star, March 3), and are keen to explain our position regarding oncology and evidence-based medicine.
The Malaysian Oncological Society (MOS) regards educating the public on cancer as one of our primary objectives and we strongly believe that the practice of oncology should be based on the best scientific evidence.
Gan’s letter raises several interesting points that continue to be debated in medicine, and science in general. Firstly, what kind of evidence is required to “prove” that something works? Is one successful case sufficient proof? Can we rely on our own, often flawed, observations to form judgements?
Work by Daniel Kahneman and Amos Tversky, recipients of the Nobel Prize in Economics in 2002, showed that men and women are inherently predisposed to errors in thinking. Mistakes due to errors in judgement have led to the tragedies caused by thalidomide and eugenics.
Medicine has wrestled with this problem for decades and thus evidence-based medicine was developed as a solution. Under this method, a new treatment is required to show strong evidence that it is effective before it is accepted by the medical community as valid.
Evidence should come from well-planned research, the observations meticulously recorded and audited independently and the results then analyzed, discussed and often debated and criticized to ensure its validity. This process is a component of evidence-based medicine and forms the foundation of modern oncology.
Another very interesting point is whether we can decide on a course of action if the scientific explanation makes sense. Thomas Huxley famously said that the great tragedy of science is the slaying of a beautiful hypothesis by an ugly fact.
Unfortunately, the history of medicine is littered with the corpses of beautiful hypotheses that turned out to be wrong or even harmful.
Angiogenesis (the formation of blood vessels to feed the cancer) was shown to be vital in the growth of cancer cells. Drugs to stop or suppress this process were shown to be highly effective in stage 4 kidney and colon cancers.
Previously, oncologists believed that it should be even more effective in earlier stage cancers as the metastatic cancer cells have not had a chance to grow or spread. However, clinical trials involving thousands of patients and doctors across multiple cancer centres did not show any benefit in adding these drugs to standard treatment.
If we had treated patients based on scientific theory that sounded reasonable without strong supportive evidence then our patients would have received ineffective therapy and be burdened with the high costs of treatment and potential side-effects. Is this acceptable to the public?
Dr Kenichiro Hasumi’s paper published in the journal Oncoimmunology in 2013 was mentioned in the letter. This paper described their experience with HITV in 167 patients with advanced cancer.
Patients received intra-tumoural injections of dendritic cells followed by high dose radiotherapy and activated T cell infusions. In patients who were treated according to their protocol, i.e. less than 5 metastases and each less than 3 cm, the clinical response rate at 1 year was 75.7%.
Fairly impressive results but this only applies to 37 out of 167 patients in the case series. Was the PETCT assessments audited by an independent external party to confirm its accuracy?
The remaining 130 patients with more extensive disease had clinical response rates of 7-13% with HITV. This is slightly better than placebo.
Are these results sufficient to be regarded as successful? If so, that is a fairly low bar. Small metastases in a limited number of sites are known as oligo-metastases. These oligo-metastases can be treated with surgery, radiofrequency ablation or high dose radiotherapy with local control rates of 70-90%.
If good response rates can be achieved with such therapies then how much can we say is due to HITV? If further distant metastases do not appear after effective local treatment in oligo-metastatic disease then we should consider the possibility that there were no metastases in other distant organs to begin with.
Therefore, the absence of relapse after high dose radiotherapy of a local recurrence in one patient is not evidence of the effectiveness of HITV.
Only a randomized clinical trial can help to answer these questions. Yes, it is costly and time consuming but it can be done. Malaysian oncologists have been participating in a clinical trial to test a virus specific T cell immunotherapy for metastatic nasopharyngeal cancer developed by a Singaporean biotechnology company. If we insist on this kind of evidence from drug companies, why should we settle for anything less from others?
The former US president Barack Obama launched the Cancer Moonshot in January 2016 with the aim of accelerating cancer research to achieve the goal of making a decade’s worth of cancer research progress in five years.
Prior to Obama’s initiative, a joint program called the Cancer Moonshot 2020 was launched by private companies and academic cancer centres aimed at developing vaccine-based immunotherapy to combat cancer. These are exciting times for oncology and we look forward to the results from their meticulous research.
We are grateful for Gan’s letter as the various thoughtful points he raised gave us the opportunity to discuss the issues we grapple with daily. The Malaysian Oncological Society is committed to insisting on the best scientific evidence to guide medical practice. Our patients have entrusted us with their lives. They deserve nothing less.
DR MUHAMMAD AZRIF
The Malaysian Oncological Society