Maybe it is time to revisit the “forgotten cousin of oncology”, aka radiation therapy, and see how it has revolutionised cancer treatment. In the immortal words of Marie Curie, who devised a way to record radiation, “Nothing in life is to be feared, it is only to be understood. Now is the time to understand more, so that we may fear less.”
There are many treatments that are initially considered bad, but when used sensibly and safely, shine. Maybe, the important issue is in the understanding that too much of anything is not great, and the balance “yin yang” is the true understanding of right.
From Hiroshima to the sun, radiation has always had bad press. What is radiation? Well ionizing radiation is emitted when radioactive substances decay. Radioactive decay occurs when the nucleus of an atom spontaneously decays by emitting a particle. In short, radiation is simply a way that energy moves around the universe. This use of energy has been harvested in oncology care. Marie Curie called this radiation radioactivity – radio means radiation.
As with all treatments, understanding the history can take away fear. Radiation history started with a German physics professor, Wilhelm Conrad Röntgen, who presented a remarkable lecture titled A New kind of Ray. It was called the X-ray as X was the algebraic symbol for an unknown quantity. Possibly, part of the hype has translated into the still unknown understanding of a treatment, that within three years, was used from diagnosis to treatment of cancer.
In France, under the Curie curatorship, major breakthroughs showed that daily doses of radiation, over several weeks, improved patients’ cures from cancer. But, as with all zealous experimentation that many scientists are prone to do; overuse and test driving of treatment on self resulted in the statement: radiation can cause cancer.
Many early radiologists used the skin of their arms to test the strength of radiation machines, looking for erythema (a pink reaction), which looked like sunburn, and was called the erythema dose. This was considered an estimate of the proper daily fraction of radiation.
Not surprising, multiple radiation exposures resulted in many, including Marie Curie, dying of leukemia due to the extensive exposure and effect of radiation on their bone marrow. (Nuked it – not Gangman Style, but Chernobyl Style.) As we listen to her words, “I was taught that the way of progress was neither swift nor easy”, one must understand that history may define progress, but it also leaves the shadows of the past in the pictures of the future.
Let’s remind ourselves, again, that cancer treament was considered the domain of the surgeon. Picture him – I see Gaston, the villain in Beauty and the Beast…maybe the perceived beast (radiation) was actually the gentle giant, and the perceived hero, Gaston, (the surgeon), who is superficially attractive, is actually lacking depth (with treatment).
So, not unlike the oncology start, radiation was considered the scraps – the last hope treatment – and, often, given last in the oncology care line, and for unresectable cancers – cervical cancers. (Don’t cry for me Argentina – Eva Peron had cervical cancer and was treated with radiation and mustard gas). But, there was some successful cancer treatment with radiation, with inoperable laryngeal cancers and cervical cancers having durable outcomes and survivals.
After WW2, cyclotrons and nuclear reactors became available and were able to produce synthetic radium and other radioactive elements for cancer treatment. The cobalt machine, using synthetic radium (1,2 MV), appeared in 1951; 1,120 machines were sold to hospitals everywhere within the first 10 years of development.
Research led to the creation of the medical linear accelerator X-ray machine (LINAC) in 1953. LINACs improved quickly and began to dominate the market. Improved cure rates followed the introduction of, first, the cobalt, and then the high-energy LINACs. Hodgkin’s lymphomas and testicle cancers became curable and a new field was born – that of radiation oncology.
The concept of nuking cells that the great surgeons could not remove with cold steel is sadly still considered a poor alterative. Steel is messy, bloody and necessary, but does not kill all cancer cells. Sometimes the power of switching off or killing the abnormal cells is more effective. Of course, trying not to convert normal cells to abnormal cells is part of the reason for the need for fine-tuning the weapon.
The addition of computers, into treament planning, improved the scrappy paper drawing as to who should get what radiation and how. Development of clever scanning devises, such as CAT-, MRI- and PET scanning, allowed tumours to be better targeted so that radiation was less of an atomic bomb.
This was followed by intensity-modulated radiation therapy (IMRT) and image-guided radiation therapy (IGRT) machinery, which used new diagnostic advances to now deliver the dose with pinpoint accuracy, while avoiding normal tissues, and thus radiation became more the focused missile – ensuring spot-on killing of cancer cells that may be outside the surgical field.
Today, conformational radiation therapy (CRT) uses CT images and special computers to verify the precise 3D map location of the cancer (like a cancer GPS), to keep the body part still, to adjust the radiation beams to the shape of the tumour and deliver the doses from several directions – high dose to the tumour bed and low dose to the surrounding tissue.
Further breakthroughs, such as stereotactic radiosurgery (SRS) (confusing as cutting is not actually done) uses a linear accelerator, or special machines, such as the Gamma Knife or CyberKnife, to deliver radiation treatment to tiny tumours in the brain or lung.
Radiation therapy has arrived, stolen the party, won the Oscar and stands on the red carpet in timeless elegance.
Intraoperative radiation therapy (IORT) is a form of treatment that delivers radiation, at the time of surgery, after the removal of the cancer. The radiation can be given directly to the cancer site or to the nearby tissues, after the cancer has been removed. IORT is thought to minimise the amount of tissue that is exposed to radiation because normal tissues can be moved out of the way, during surgery, and shielded, allowing a higher dose of radiation to the tumour bed. This treatment is available for certain pelvic and abdominal cancers, as well as certain breast cancers.
Over a 60-year period, the great weapon of radiation was fined-tuned. It was critical in the trials of breast-conserving surgery for breast cancer. These trials, performed in the 70s, showed that breast-conserving surgery with radiation on the remaining breast had equivalent survival outcomes to a mastectomy without radiation.
The initial trials did not have the most appeallling aesthetic outcomes. Firstly, the surgery often involved removing at least a quarter of the breast, without close attention as to how the remaining hole was to be filled. The initial surgical concept, of allowing the fluid produced by the body (serous fluid) to accumulate and fill the area excised, gave a short-term nice-looking breast, but a long-term distorted breast. The radiation doses weren’t so accurately accessed. The addition of a boost, showing decreased local cancer recurrence in the area, also resulted in compounding the not-so-attractive result.
The initial requirements for radiation were determined on several good randomised trials and meta-analyses, showing similar survival rates between breast-conserving surgery with radiation and mastectomy without radiation.
The National Surgical Adjuvant Breast and Bowel Project (NSABP) B-06 trial and others showed that after removal of the breast cancer with microscopic clear margins, irradiation of the whole breast, with a dose of 50Gy, reduced the rate of local breast cancer recurrence. Addition of a boost to the tumour bed, further decreased the local cancer recurrence.
So as the field of radiation started to fine-tune its techniques, so did the understanding of when it should be used. This is important, as I believe that the forgotten cousin, who is always the last to be invited to the oncology dinner party, has finally come into her own.
The basis of most consensus statements in oncology care is not based on a whim and a prayer, but rather on many trials looking at outcomes. Like with all treatments, fundamental rules came into play. The initial breast rules for radiation were as follows:
• All women getting breast-conserving surgery should have whole breast radiation (including a boost to the tumour bed).
• All cancers bigger than 5cm should have radiation.
• All T4 breast cancers should have radiation treatment – this included involvement of the chest wall, often clinically or radiologically assessed as cancers involving the pectoralis muscle, the skin of the breast from attachment too, through to the skin and inflammatory breast cancer: red breast, orange peel effect (peau d’orange) on the breast.
BIG DEBATE – WHO GETS RADIATION?
The sticky subject of who should get radiation after a mastectomy, if close cancer margins are involved, remains a debate that is a bit like politics and religion. Margins and breast cancer management is a tricky issue (near and dear, and my grey hair inducing – breathe in). So here goes: I take the Fifth, and suggest that whatever your unit selects as a clear margin around cancer is good enough, as long as they justify the reasons for the choice. Clear margins from cancer to normal tissue differs with regards to breast-conserving surgery and mastectomies. My rule around margins and mastectomies is: don’t replace poor surgical margins with radiation. If you can avoid radiation with a clear surgical margin, please do!
When it comes to the axilla (armpit) regional lymph node drainage, there has been a huge change in what to radiate, why and when. The current recommendations are that all women with cancers in the lymph nodes should get radiation. This is based on a 2013 consensus statement.
It is also interesting to note, that it is not necessary in women with a positive sentinel lymph node biopsy; that they may not require a full axillary dissection (now defined as taking seven or more lymph nodes), but that they can have radiation instead, to axillary lymph node basin. This makes for the most important aspect of defining who gets radiation.
Save the last dance for me
A large number of women who are diagnosed with breast cancer are often started with primary oncology (most often primary chemotherapy). Remember, that oncology treatment (drugs to treat breast cancer) is the umbrella underwhich all treatment sits. The oncology umbrella protects people from the acid rain of cancer (no one dies from breast cancer in the breast, but rather from the ability of cancer cells to behave like terrorists, and go and form terrorist cells elsewhere, that can wake up, many years later, to perform dastardly deeds, such as 911, on bodies).
It is for this reason, and the reason that radiation treatment is often performed after chemotherapy and surgery, that it is critical to understand the indications upfront, and a discussion of all patients is held in a multi-disciplinary meeting (MDM), and ensuring that the treatment team has documented the need for radiation. I often see patients, after they have started the primary/upfront chemotherapy, and the following information has not been documented.
Did the original mammogram and, more importantly, the ultrasound document whether the radiologist could see cancer in the lymph nodes? Ultrasounds, in the hands of a good radiologist, can detect cancer in the lymph nodes with a 95%+ accuracy. Was a marker, called a V-marker, placed into the centre of the breast cancer prior to starting chemotherapy? This is critical, as it helps work out the area the surgeon needs to remove post chemotherapy. It is not necessary to remove the whole breast or the original size of the cancer after chemotherapy has killed it, but merely the leftover area, and then follow this up with radiation treatment to stun the area.
The concern about radiation is always the fact that it is given over small doses, over a period of time, and the nuisance factor is the going every single day – Monday to Friday – to the nearest appropriate unit.
I always say that chemotherapy is the extreme event – climbing the mountain, running the marathon – whereas surgery is when you feel broken at the finish line, and radiation is walking off the field. You’re sick and tired of treatment, and now need to go to the same takeaway venue each day. Of course, this is exhausting! It takes longer to drive there, park and get out the car, than the five minutes of treament per day.
Radiation has not only recently been shown to improve local outcomes, but improves cancer survival in its own right. What I can tell you, is that Marie Curie’s sad party dress quote, “I have no dress except the one I wear every day. If you are going to be kind enough to give me one, please let it be practical and dark so that I can put it on afterwards to go to the laboratory” has been transformed into a little black dress – a Chanel classic! Radiation therapy has arrived, stolen the party, won the Oscar and stands on the red carpet in timeless elegance.