Risk Assessment for Hodgkin Lymphoma Evolving and Promises Greater Precision and Specific Clinical Relevance

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“Risk assessment in Hodgkin lymphoma is continuously evolving and promises even greater precision and specific clinical relevance in the future,” Joseph M. Connors, MD, stated in Blood. Dr. Connors is Clinical Professor, British Columbia Cancer Agency Centre for Lymphoid Cancer and the University of British Columbia, Vancouver, Canada.

“Careful assessment of the amount of the lymphoma (tumor burden), its behavior (the extent to which it has invaded or compromised specific organ function), and special host-related factors (age, coincident systemic infection and organ dysfunction, especially of the hematopoietic system, heart, and lungs) is essential to optimize treatment outcome,” Dr. Connors wrote.

Patient-related risk factors include age, gender, human immunodeficiency virus (HIV) infection, and organ compromise. “Previously acquired pulmonary compromise, usually related to cigarette smoking, may necessitate omission of bleomycin from primary treatment,” Dr. Connors noted. “Deciding when to drop bleomycin is made more challenging due to the lack of useful objective screening assessment tools” and  “must be made on clinical grounds,” Dr. Connors stated.

“I have found a useful rule of thumb is to consider the potential impact of a relatively rapid loss of 30 % to 40 % of current respiratory reserve. If a patient appears, based on a review of current activity levels and exercise tolerance, capable of absorbing that much loss of lung function from current pulmonary reserve, bleomycin can be safely, but still carefully, included in planned chemotherapy,” Dr. Connors advised. “If I do not think such a loss could be endured safely, I omit bleomycin, at least until pulmonary reserve improves.”

Underlying cardiac disease may affect the safe use of anthracyclines. “A history of congestive heart failure or ongoing evidence of impaired cardiac reserve such as a left ventricular ejection fraction less than 50% should prompt careful consideration of the risk that exposure to doxorubicin or doxorubicin plus mediastinal radiation will worsen underlying cardiomyopathy. In such cases, careful serial monitoring of ventricular function must be included in the patient’s assessments during treatment, and omission of the anthracyclines and substitution with an alternative chemotherapeutic agent such as etoposide should be considered,” according to Dr. Connors.

Older age has consistently been shown to have an adverse impact on the treatment of Hodgkin lymphoma. “The challenge when considering age is that it is in many ways simply a proxy for physiologic function. Ignoring age places the patient at exaggerated risk, but unduly emphasizing it risks undertreatment.” Dr. Connors noted.

Along with assessing specific organ function, “a reasonable and practical approach to adjusting treatment based on age is to start treatment with a modest dose reduction by 20% to 30% of the myelosuppressive chemotherapy agents but subsequently to escalate to full doses with subsequent cycles, seeking to reach the maximum that can be achieved without undue toxicity as early in overall treatment as feasible.”

The impact of stage of disease and other clinical factors “has diminished substantially as the effectiveness of interventions has improved,” Dr. Connors noted. “Elaborately assembled prognostic factor scoring systems, such as the International Prognostic Factors Project score, have lost much of their accuracy and value as increasingly effective chemotherapy and supportive care have been developed,” he added.

A growing number of specific biomarkers are being identified and linked to risk. For example, increased expression of antigens expressed by Hodgkin Reed-Sternberg cells can be assessed at the time of diagnosis and may predict a worse outcome. Other biomarkers promise further improvement in targeted therapy, which increases effectiveness but decreases off-target toxicity.

“Parallel developments in the application of functional imaging are bringing additional potential to evaluate the efficacy of treatment even as it is being delivered, allowing dynamic assessment of risk in the midst of chemotherapy and adaptation of the treatment regimen in real time,” Dr. Connors added. ■

Connors JM: Blood 125:1693-1702, 2015.