Treatment Outcomes

Two major papers consider the long-term and short-term outcomes of paediatric low-grade glioma patients having received mainstream treatments.

Long-Term Outcomes

A study called "Clinical and Treatment Factors Determining Long-Term Outcomes for Adult Survivors of Childhood Low-Grade Glioma: A Population-Based Study" looked at determining factors for the survival rate of 1202 children in Ontario, Canada, diagnosed with low-grade gliomas between 1985 to 2012. The study shows that children with low-grade gliomas have an excellent chance of surviving into adulthood, but a major risk factor was radiotherapy:

1. At a follow-up of just over twelve years, there were only 93 deaths, which is a survival rate of 7.7%.
2. The twenty-year overall survival rate was 90.1%.
3. A thalamic tumour location adversely affected the long-term survival rate, but most of those who had died had received upfront radiotherapy.
4. Upfront radiotherapy had a 3-fold increased risk of overall late death.
5. Upfront radiotherapy had a 4-fold increased risk of tumor-related deaths.
6. Late mortality was not often due to tumour progression, but rather, due to tumor transformation and non-cancerous causes.

The study concludes that:

"The course of pediatric low-grade glioma is associated with excellent long-term survival, but this is hampered by increased delayed mortality in patients receiving upfront radiotherapy. These observations should be considered when treatment options are being weighed for these patients."

Shorter-Term Outcomes

The study HIT-LGG 1996, investigated shorter-term treatment outcomes for 1031 children with low-grade gliomas. A 2012 edition of the Journal of Neuro-Oncology reported the results.

Tumours were fully removed surgically in over a third of the cases, 359 children in total. Of the other 672 children, doctors put 488 under observation because they had not displayed any symptoms. That meant that 849 children were under a ‘watch and wait’ regimen. Unfortunately, just under half of those 849 children suffered tumour regrowth, of whom, about a fifth, 65 children, remained in a ‘watch and wait’ mode. However, one-third, 102 children, had more surgery. The rest, 179 children, went on to receive either chemotherapy or radiotherapy. They joined another 184 children who received, either post partial resection or as a first-line treatment, non-surgical adjuvant therapy. That meant that 363 children received non-surgical treatments. 216 of those children underwent the chemotherapy regimen of Carboplatin and Vincristine and 193 out of those were still alive at the time of the report, which equates to a 10-year survival rate of 89%. The remaining 147 of those 363 children received radiotherapy, of whom, 136 were still alive, which is a 92% survival rate. The best outcome, however, was with the 668 children watching and waiting. Of these, 643 were still alive, which is a ten-year survival rate of 96%.

The journal’s conclusion highlights how well chemotherapy delayed or avoided radiotherapy. To this end, the authors judged the treatment a success; 91.9% of its patient’s tumours responded to treatment, with irradiation deferred for between 4 months and 8.7 years. Furthermore, 141 of the 193 surviving chemotherapy patients had not needed radiotherapy at all. However, the conclusion fails to highlight that about 15% of the chemotherapy patients experienced tumour progression within the first year after treatment, and progression-free survival apparently decreased year on year. Half of the chemotherapy patients also experienced hematotoxicity (a reaction which destroys red blood cells) and a further 53% also suffered an allergic reaction. Unfortunately, the study did not detail the problems such reactions caused. Neither was the toxicity for the radiotherapy group recorded. Radiotherapy also fairs badly overall (no matter what toxic reactions its patients had experienced), with nearly 4 out of 10 patients requiring further treatment for tumour progression. The article’s conclusion also fails to comment on the slightly higher mortality rate of chemotherapy, as opposed to surgery or radiotherapy.

The study suggests that the best outcome, given the presented data, was from surgical intervention, with over half of the children that had received surgery achieving an event free 10-year survival rate, whether they had been given a complete resection or not:

Primary safe tumour resection is the treatment of choice for LGG.

The journal’s authors also considered ‘watch and wait’ as a viable treatment:

Observation was recommended following complete tumour resection, as well as in cases of incomplete or no surgery if presented without significant clinical symptoms or progression.

And:

Observation was recommended following complete tumour resection, as well as in cases of incomplete or no surgery if presented without significant clinical symptoms or progression.

The Hippocratic Oath

Primum non nocere is a Latin phrase that means: “First, do no harm”. It forms the basis of the Hippocratic Oath, an ancient rite of passage for practitioners of medicine. Though there is no legal obligation to swear on this oath, medical students around the world swear by it in some form. It reminds doctors that they must first consider the damage that treatment might cause. In fact, the oath teaches that it might be best to do nothing at all. Below is a translation:

I swear by Apollo, the healer, Asclepius, Hygieia, and Panacea, and I take to witness all the gods, all the goddesses, to keep according to my ability and my judgement, the following Oath and agreement:

To consider dear to me, like my parents, him who taught me this art; to live in common with him and, if necessary, to share my goods with him and to look upon his children as my brothers. To teach them this art; and that by my teaching, I will impart a knowledge of this art to my sons, and to my teacher’s sons, and to disciples bound by an indenture and oath according to the medical laws, and no others.

I will prescribe regimens for the good of my patients according to my ability and my judgement and never do harm to anyone. I will give no deadly medicine to anyone if asked, nor suggest any such counsel. Similarly, I will not give a woman a pessary to cause an abortion.

But I will preserve the purity of my life and my arts. I will not cut for stone, even for patients in whom the disease is manifest; I will leave this operation to be performed by practitioners, specialists in this art.

In every house where I come, I will enter only for the good of my patients, keeping myself far from all intentional ill-doing and all seduction and especially from the pleasures of love with women or men, be they free or slaves.

All that may come to my knowledge in the exercise of my profession or daily commerce with men, which ought not to be spread abroad, I will keep secret and will never reveal.

If I keep this oath faithfully, may I enjoy my life and practice my art, respected by all humanity and in all times; but if I swerve from it or violate it, may the reverse be my life.

“First, do no harm”. That fundamental principle of the Hippocratic Oath teaches doctors that they should take a holistic view and understand the full effects of the treatments they prescribe. Pediatric brain tumours are a difficult disease. However, Hippocratic principles still need considering. As Cancer Research UK puts it:

"As more and more people are surviving their childhood cancers, the long-term effects of treatments suffered by a significant proportion of survivors are also becoming increasingly important. Developing treatments with minimal negative effects (to achieve “cure at least cost” rather than “cure at any cost” ) is also an important research focus for the future."

The bigger picture must be whether or not a child suffers other diseases or has physical and mental impairment because of treatment. The Ontario study shows that radiotherapy may not be the best primary treatment for children with low-grade gliomas. Indeed, the conclusion must be that radiotherapy should only ever be the treatment of last resort.

Christiaan Barnard, a South African cardiac surgeon who performed the world’s first successful human-to-human heart transplant, had the Hippocratic Oath very much in mind, when he put it this way:

“The prime goal is to alleviate suffering, and not to prolong life. And if your treatment does not alleviate suffering, but only prolongs life, that treatment should be stopped.”