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SRI Magazine 2016

SRI Magazine 2016

Studies help blood cancer patients make treatment decisions

New risk score is more comprehensive than previous one, and only chemotherapy in early-stage disease a viable option for some

“I will remember that I do not treat a fever chart, a cancerous growth, but a sick human being, whose illness may affect the person's family and economic stability.”

When graduating medical students recite the modern version of the Hippocratic Oath they are pledging to treat their patients as more than a presentation of ailments and symptoms. Each person has a unique story that can affect the course of the disease and treatment. In conversations frequently dominated by jargon and numbers, however, the patient’s voice can sometimes be lost.

At Sunnybrook Research Institute, Drs. Rena Buckstein and Matthew Cheung are striving for change. These scientists are showing how inclusion of patient-specific traits and perspectives can improve risk assessment and treatment decision-making.

Buckstein is an oncologist who specializes in haematological cancers, those of the blood. She is also the co-director of the myelodysplastic syndrome (MDS) research program at Sunnybrook’s Odette Cancer Centre. Myelodysplastic syndromes are a group of cancers that have in common faulty blood stem cells. In healthy people, blood stem cells mature into new red and white blood cells and platelets, which deliver oxygen, fight infections and form blood clots to stop bleeding, respectively. In patients with MDS, the stem cells fail to develop properly, leading to a shortage of healthy blood cells and platelets. Consequently, patients with MDS are prone to anemia, infections, bleeding and bruising. Most will require blood transfusions, and one-third will develop acute leukemia.

“The average age of diagnosis [for MDS] is about 72,” says Buckstein. “The prevalence is increasing because more and more people are living beyond the age of 70.”

The elderly patient presents a unique set of challenges when it comes to assessing risk and determining prognosis. Chief among them are frailty and the chronic health conditions, or comorbidities, many patients have in addition to MDS. The tools physicians use to calculate risk, like the revised International Prognostic Scoring System (IPSS-R) app Buckstein pulls up on her iPhone, rely primarily on lab test results. She types in a few numbers for a ficti­­tious patient—age, platelet counts, blood cell counts, percentage of immature blood stem cells, genetic abnormalities—and almost instantly, the app generates a risk score and projected survival.

“Haematologists love risk scores,” she says. While handy, the IPSS-R score is incomplete. “You have no real good way of telling someone how their level of comorbidity or frailty is going to impact on their disease course. That’s never been incorporated into any scores.”

To determine whether comorbidity and frailty could be used to refine the IPSS-R, Buckstein and Dr. Richard Wells, co-director of the MDS research program, founded a national MDS registry, the first of its kind in Canada. In addition to their medical history, patients enrolled in the registry were asked about their quality of life and other medical conditions such as heart disease, diabetes and previous cancers. Patients were also evaluated for disability and frailty using a variety of tests done when they first joined the registry and once a year thereafter.

You can’t treat the disease in isolation.

By following patients an average of 20 months, the researchers found that combining IPSS-R with new scores for frailty and other health conditions generated a comprehensive score that could predict overall survival more accurately. The addition of frailty and comorbidity scores to the IPSS-R increased its predictive power by 35% relative to the IPSS-R score alone. This study is the first to examine the effects of frailty on predicting survival in patients with MDS. It was published in the British Journal of Haematology.

“You can’t treat the disease in isolation,” says Buckstein. “Patient-related factors [like frailty and comorbidity] have to be incorporated into our scoring systems that predict outcome so that we can better counsel our patients and inform our physicians.”

Cheung, a scientist and physician at Sunnybrook who specializes in blood disorders, is also advocating for a patient-centred approach. He recently completed an evidence-based review to address the controversy surrounding radiation therapy in treatment of early-stage Hodgkin lymphoma (HL), a cancer that originates in white blood cells called lymphocytes.

The standard of care for patients with early- or limited-stage lymphoma is chemotherapy followed by radiation. Despite being a mainstay of HL therapy, radiation carries considerable risk—it can damage DNA and cause healthy cells to turn cancerous. Most cases of HL start in lymph nodes found in the neck and chest. Irradiation of these areas not only kills the cancerous lymphocytes, but it can also increase the risk of early heart disease and secondary cancers developing in neighbouring tissues like the breast, thyroid and lung.

“In the last decade, we’ve become very successful at treating HL, especially limited-stage HL,” says Cheung. “These patients have a very good long-term prognosis. But then we worry that in the five-, 10-, 15-year timeframe, are they going to run into these [other] problems that we caused?”

Concerns over secondary cancers and early heart disease have pushed into practice guidelines that reduce the area receiving radiation and the dosing of this treatment, thereby lessening exposure. Cheung wanted to go one step further by asking: Can you minimize risks from radiation exposure by forgoing it altogether?

He combed through the scientific literature looking for studies comparing survival of patients with HL who received chemotherapy and radiation to that of patients who received chemotherapy alone. He found that although fewer patients treated with both therapies saw their lymphoma progress after treatment, patients who received only chemotherapy had lower incidences of secondary cancers and heart disease and higher survival rates overall. In other words, patients treated with chemotherapy alone fared just as well in the long term as those who received combination therapy.

Still, Cheung points to an important caveat of the earlier study comparing the two treatment strategies: the dose of radiation given to the patients was much higher than the dosing typically used today. While more research is needed to compare directly chemotherapy with and without modern radiation therapy, his findings have led to a new Cancer Care Ontario guideline on how physicians should discuss treatment options with patients who have early-stage HL.

“Because of [this review], our general feeling is that a chemotherapy-alone approach is a reasonable option in some patients,” says Cheung. “Obviously, there’s still some controversy, and there’s no 100% certain approach. That’s why we really value the patient’s thoughts in this process.”

He notes some patients might prefer the more aggressive approach with chemotherapy and radiation to try and cure the lymphoma at any cost. Others, such as those with a higher risk of developing breast cancer, might opt for a more conservative approach and choose chemotherapy alone. Although chemotherapy alone may be slightly less effective at treating HL upfront, it is still an excellent option offering a high likelihood of cure and potentially is safer in the long run.

“In the past, a lot of decisions were set out in HL and almost dictated to the patient,” he says. “Our hope is this paper gives both physicians and patients a chance to have a dialogue where patients can make a decision.”

Buckstein’s research is funded by the Canadian Institutes of Health Research, Celgene Canada and the Crashley Estate. Cheung’s research is funded by the Cancer Care Ontario program in evidence-based care and the support of Roy and Majorie Linden, and Joan Fisher and James Rowland.