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


Key Points

  • Continuously evolving risk assessment in Hodgkin lymphoma points toward greater precision and specific clinical relevance.
  • Careful assessment of the tumor burden, the extent of organ invasion or compromise, and patient-related factors such as age is essential to optimize treatment outcome. 

“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.

Careful assessment of tumor burden, its behavior, and host-related factors such as age, coincident systemic infection, and organ dysfunction (especially of the hematopoietic system, heart, and lungs) is essential to optimize treatment outcome, Dr. Connors wrote.

Pulmonary Compromise and Underlying Cardiac Disease

Patient-related risk factors included 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,” Dr. Connors advised. If, based on a review of current activity levels and exercise tolerance, a patient appears capable of absorbing that much loss of lung function from the current respiratory reserve, bleomycin may be included in the planned chemotherapy. However, if such a loss could not be endured safely, bleomycin should be omitted until pulmonary reserve improves, he said.

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,” according to Dr. Connors. Cases such as these require careful serial monitoring of ventricular function in the patient’s assessments during treatment, and omission of the anthracyclines and substitution with an alternative chemotherapeutic agent should be considered, he noted.

Age as Proxy for Physiologic Function

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 to subsequently 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.

Parallel Developments in Biomarkers and Functional Imaging

A growing number of specific biomarkers are being identified and linked to risk. For example, increased expression of antigens noted 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.

Dr. Connors is the corresponding author of the Blood article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.