TREATMENT OF EARLY STAGE HODGKIN LYMPHOMA

NEW YORK (Reuters Health) - Fewer than half of early-stage Hodgkin lymphoma (HL) patients receive combined-modality therapy (CMT) that could prolong their survival, according to an analysis of the National Cancer Data Base (NCDB).

"We showed that the clinical practice in the U.S. is skewed away from combined-modality therapy in a manner that seems excessive and not motivated by evidence," Dr. Adam J. Olszewski from Alpert Medical School of Brown University, Providence, Rhode Island, told Reuters Health by email.

"In our data all patient subsets identified by clinical variables (age, sex, detailed stage or histologic subtype) had similar survival advantage with combined-modality therapy, he continued. "Therefore, it should be offered as a standard of care for all patients, and they should know that there may be an overall survival disadvantage to using chemotherapy only - even if a small one."

"The apparently widespread fear that administration of radiation might increase mortality for younger patients is unjustified, although this is a group that is particularly receiving less and less of combined-modality approach," he said.

Because of the late toxicities of radiation, there has been ongoing interest in identifying groups of patients with early favorable HL who might be cured with chemotherapy alone, but this strategy remains controversial.

Dr. Olszewski's team used NCDB data from 20,600 patients with early-stage HL to identify factors determining the choice of treatment, CMT or chemotherapy alone, and to assess the impact of this choice on survival.

Just under half of the patients (10,200; 49.5%) received CMT, and its use declined from 59.4% in 2003 to 45.2% in 2011, according to the January 12 Journal of Clinical Oncology online report.

The odds of receiving CMT were lowest in the youngest age groups and were significantly lower in black patients and in those who were uninsured or who had Medicaid or Medicare coverage. CMT utilization was lower in academic centers and when the distance to the treatment facility exceeded 50 miles.

Patients with B symptoms (fever, night sweats, and weight loss), subdiaphragmatic tumors, or lymphocyte-depleted histology were less likely to receive CMT.

After adjustment for various factors, estimated 5-year overall survival was significantly better for patients treated with CMT (94.6%) than for patients treated with chemotherapy alone (90.9%).

Relative survival (a proxy for lymphoma-specific survival) was also better after CMT (97.5%) than after chemotherapy alone (94.1%).

"Clinicians should realize that the purported problems with combined-modality therapy (risk of secondary cancers) were detected in the era of outdated treatment paradigms (extensive radiation fields, high radiation doses), and it is not at all certain how relevant they are to current techniques," Dr. Olszewski said.

"They should also pay attention to the evident disparity in treatment selection and focus their efforts on helping disadvantaged patients (racial minorities, the uninsured and Medicaid recipients) complete the combined-modality therapy rather than limit the treatment to chemotherapy only," he continued.

"The data suggest that some U.S. clinicians adopt a very aggressive approach and deliver both a long (6-month) chemotherapy and more than 30 Gray of radiation," he said, "but clinical trials have shown that as little as two months of chemotherapy and lower doses of radiation are sufficient for most early-stage patients with no risk factors."

"We are all interested in curing as many patients as possible while minimizing side effects of therapy," Dr. Olszewski concluded. "If we are uncomfortable with the perceived risks of combined-modality therapy, we must do our best to investigate alternative approaches that can achieve this goal without sacrificing efficacy."

"We should improve the existing system to collect more treatment-oriented data, which can allow us to study what patients and doctors care about most: treatment effects and optimal decision-making," Dr. Olszewski added.

"Unfortunately the limitations in the data available to the authors of this article were too substantial for meaningful conclusions to be drawn about best approach to treatment for any individual patient," said Dr. Joseph M. Connors from British Columbia Cancer Agency Center for Lymphoid Cancer and the University of British Columbia, Vancouver, in email to Reuters Health.

"Their data suggest some interesting, potentially testable hypotheses but do not provide adequately specific information to guide treatment," he continued.

The following, he pointed out, were lacking in the researchers' dataset: number of sites of disease; bulk of disease; performance status; organ function; details of treatment (including type of chemotherapy and number of cycles); methods of assessment of treatment response, and timing of treatment assessment.

"Choice of treatment for Hodgkin lymphoma should be based on evidence," Dr. Connors concluded. "That evidence needs to include much more specific information than these authors had available."

Dr. Joachim Yahalom from Memorial Sloan-Kettering Cancer Center, New York, told Reuters Health by email, "Survival of early stage HL patient has continued to improve since the 1970s until recently. With the trend of trusting (more) chemotherapy alone and avoiding radiation therapy, are we going to observe a decline in survival curves as this data would suggest? This is worrisome at the national level judged by the NCDB data."

"I think that at the very least we should follow the 2014 UK recommendations for HL that in summary advocated CMT as the standard treatment and that 'the decision to omit radiation therapy from the management of stage IA/IIA non-bulky patients should involve discussion with a radiation oncologist, and patients choosing to omit radiation therapy need to be aware of the balance of risks between radiation therapy and additional cycles of chemotherapy,'" Dr. Yahalom said. "I hope that the U.S. National Comprehensive Cancer Network (NCCN) guidelines will be modified to reflect this approach and practitioners will be alerted to data that omitting radiation therapy will affect the outcome of this group of highly curable patients."

Finally, Dr. Stephen M. Ansell from Mayo Clinic, Rochester, Minnesota, told Reuters Health by email, "Combined-modality therapy remains the standard of care for early-stage Hodgkin lymphoma, and in population-based studies such as this one, CMT is associated with better outcomes when compared to chemotherapy alone."

"While there is a trend in the oncology community toward giving chemotherapy alone based on concerns about toxicity associated with radiotherapy, the results of this study suggest caution as decisions to standardly omit radiotherapy may impact patient outcome," he continued. "Outside of a clinical trial, it is still standard to give CMT, and decisions to give chemotherapy alone simply based on convenience or cost should be avoided."

"While it may be tempting to omit radiation therapy and give chemotherapy alone in early-stage Hodgkin lymphoma, this decision should be carefully considered," Dr. Ansell concluded. "While a chemotherapy-only approach may be perfectly reasonable in certain circumstances and settings, omitting radiotherapy in general practice may compromise patient outcome."

SOURCE: http://bit.ly/1DGtzMi

J Clin Oncol 2015.