Currently, most patients are overtreated because there has been no way to identify the small subgroup — about 15% to 20% of the patient population — with a poor prognosis. But now it appears that there is a way to do this, and it is relatively simple, said Vincent T. DeVita Jr., MD, Amy and Joseph Perella Professor of Medicine at Yale Cancer Center, Yale School of Medicine, in New Haven, Connecticut. He was referring to new research published March 11 in the New England Journal of Medicine, which he welcomed enthusiastically.
This finding appears to be "the breakthrough we have been looking for," Dr. DeVita writes in an accompanying editorial, which he coauthored with his Yale colleague, José Costa, MD. It should "bring more logic to the treatment of this curable cancer."
In an interview with Medscape Oncology, Dr. DeVita added that "this could change the whole landscape of treatment for Hodgkin's lymphoma."
New Biomarker for Risk Stratification
The new test was developed in a 2-stage process. In the first stage, the researchers conducted an analysis of 30 fresh-frozen tissue samples obtained from patients with classic Hodgkin's lymphoma during diagnostic lymph-node biopsy. From this, they identified a gene signature of tumor-associated macrophages that was significantly associated with primary treatment failure (P = .02). The team then confirmed the finding, using immunohistochemical analysis, in an independent cohort of 166 patients.
"An increased number of tumor-associated macrophages was strongly associated with shortened survival in patients with classic Hodgkin's lymphoma, and provides a new biomarker for risk stratification," the researchers conclude.
The tumor-associated macrophages were identified by a single marker of CD68+ cells in the immunohistochemical analysis, which can easily incorporated into a routine diagnostic workup, the team notes.
The first stage of this research — the identification of the gene signature — required a very complicated methodology and fresh-frozen tissue, Dr. DeVita told Medscape Oncology. However, the second part of this research — validation in a independent set of patients — was straightforward and required only paraffin-fixed material for immunohistochemistry analysis of diagnostic biopsy samples. "This is apple-pie easy," he said, adding that "any pathology department can do this." He predicted that many will start doing it as soon as they read the paper, and he encouraged researchers with access to large number of samples to do so to validate these new findings.
"It is important to get this validation by an independent group," he said, "but I do not think that a randomized trial is necessary."
Potential Impact on Clinical Practice
If other groups confirm this finding, it could have a big impact on clinical practice, Dr. DeVita predicted. It will allow the subgroup of patients with Hodgkin's lymphoma who have a poor prognosis to undergo aggressive treatment with both radiotherapy and combination chemotherapy.
At the same time, it would spare the majority of the patients from overtreatment, he said. Hodgkin's lymphoma has been curable now for more than 40 years, but most patients with this disease are overtreated, and this is a "ludicrous situation," he said. There is an ongoing debate over the use of radiotherapy for Hodgkin's disease, as previously reported by Medscape Oncology, with opponents arguing that it is more harmful than beneficial. Despite the ongoing debate, many patients still receive radiotherapy, Dr. DeVita noted, even though it causes long-term damage. For example, radiotherapy for Hodgkin's disease in women raises their risk for breast cancer by 30% to 35% at 15 years, he explained.
This new test would identify the 80% to 85% of patients who have a good prognosis and would be expected to respond well to chemotherapy, and Dr. DeVita suggested that this group should be treated with chemotherapy alone, although he acknowledged that "there are other opinions on this, and radiotherapists would argue against this."
Benefits to Patients
Coauthor of the paper, Joseph Connors, MD, chair of the Lymphoma Tumor Group at the British Columbia Cancer Agency in Vancouver, said that this new test has the potential to benefit 2 patient groups. It can identify the approximately 20% of patients "who are currently not doing well with our best treatments, so that fewer than half are cured," he said in an interview. This group could be the subject of research, with a view to intensifying treatment or trying new treatments to improve the cure rate. At the same time, the remaining patients — who do well on current treatment — could also benefit; in this group, "we could compare the current treatments and choose from them the approach that causes the least long-term injury," he said, minimizing treatment-related risks later in their life.
The research reported by Dr. Connors and colleagues indicates that it is the patients with high CD68+ counts who have the poor prognosis. This CD68+ measure "represents a biomarker with clinical applicability in all stages of classic Hodgkin's lymphoma, both at the time of diagnosis and at the time of relapse." It can predict the outcome of both primary and secondary treatment (in particular, autologous stem-cell transplantation), they point out.
Dr. Connors explained that, to date, Hodgkin's lymphoma patients have been categorized as having limited disease, where the lymphoma is found only in a small region, and advanced disease, where the lymphoma is found in many parts of the body. The 2 are treated differently, mainly in the total amount of exposure to chemotherapy, and sometimes radiation is added, he said.
The new test that measures CD68+ has found high levels of this marker in both sets of patients, but proportionately, there are more patients with advanced disease who also have high levels of CD68+, and there are fewer patients with limited disease who have high levels of CD68+, he said.
With current treatment, about 90% to 95% of patients with limited disease are cured, and about 70% of those with advanced disease are cured, Dr. Connors said. "But we have had no way of identifying that small group of patients who are not cured, as they all look alike," he said. "This new test has the potential to identify that small group of patients, and will allow us to offer them extra treatment," he explained.
Dr. Connors and his coauthors have disclosed no relevant financial relationships, except senior author Randy Gascoyne, MD, from the Department of Pathology and Laboratory Medicine at the University of British Columbia, in Vancouver, who reports receiving consulting fees from Genentech, Roche Canada, and Eli Lilly, and research support from Roche Canada. Both editorialists have disclosed no relevant financial relationships.
N Engl J Med. 2010;362:875-885, 942-943.
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου