Vo2peak in Adult Survivors of Hodgkin Lymphoma: Rate of Decline, Sex Differences, and Cardiovascular Events

Abstract

Background: Adult survivors of Hodgkin lymphoma (HL) are at increased risk of cardiovascular (CV) events secondary to mediastinal radiation therapy (RT).

Objectives: In this group of patients, we assessed the association between cardiopulmonary exercise testing (CPET), as determined by percent-predicted peak Vo₂ (ppVo₂peak), and clinical outcomes, as well as the rate of ppVo₂peak decline and sex differences.

Methods: All survivors of HL who were >10 years post chest RT and who underwent ≥1 CPET were enrolled from a single center. Traditional CV and treatment risk factors, along with CV events, were ascertained.

Results: A total of 64 patients (67% female; median age 51 years [range 26 to 70 years]) with a median follow-up time after RT of 23 years (range 11 to 41 years), and 141 CPET studies, were included. Median initial ppVo₂peak was 91% (range 58% to 138%). ppVo₂peak in survivors declined by 7.5 percentage points every 10-year period after RT, as compared with age- and sex-based norms (P = 0.001), even after adjusting for hypertension and history of anthracycline. Both male and female patients had a similar rate of ppVo₂peak decline. However, women had a lower ppVo₂peak at all times, and they developed abnormal ppVo₂peak (≤85%) on average earlier than men (24.1 years vs 47.0 years after RT). Patients with abnormal ppVo₂peak vs normal ppVo₂peak (>85%), had an increased risk of CV events (59% vs 16%). Abnormal ppVo₂peak was independently associated with the risk of CV events (adjusted HR: 6.37; 95% CI: 2.06-19.80; P = 0.001).

Conclusions: Percent-predicted Vo₂peak in long-term survivors of HL who were treated with chest RT progressively declined as compared with population- and sex-based norms. Importantly, women developed abnormal ppVo₂peak more than 2 decades earlier than male survivors. Abnormal ppVo₂peak was associated with an increased risk of CV events in this group of patients.

Keywords: BCH, Boston Children’s Hospital; CPET, cardiopulmonary exercise testing; CV, cardiovascular; HL, Hodgkin lymphoma; Hodgkin lymphoma; LSM, least squares mean; RER, respiratory exchange ratio; RT, radiation therapy; Vo2; cardiac events; cardiopulmonary test; ppVo2peak, percent-predicted peak volume oxygen; radiation; sex; women.

Graphical abstract

Figure 1

Decline of ppVo₂peak Over Time After Radiation Therapy (Top) Least squares mean percent-predicted peak Vo₂ (ppVo₂peak) decreased by 7.5 percentage points every 10 year-interval after radiation therapy (P = 0.001) (0.75 percentage point decrease per year, assuming a linear decline after 10 years from radiation exposure). (Bottom) The percentage of abnormal cardiopulmonary exercise testing (CPET) results (ppVo₂peak ≤85%, shaded) increased over time. At 40 years after radiation therapy, 100% of cardiopulmonary exercise testing results had abnormal ppVo₂peak.

Figure 2

Rate of ppVo₂ Decline by Sex Least squares mean percent-predicted peak Vo₂ (ppVo₂peak) decreased at a similar rate for both male (blue) and female (yellow) patients, but it was lower for female patients at all times. Least squares mean ppVo₂peak in female patients was abnormal (≤85%) 22.9 years earlier than in male patients, as represented by the intersection of dotted vertical lines and the solid horizontal line.

Central Illustration

Cardiopulmonary Testing in Hodgkin Lymphoma Survivors Treated With Chest Radiation Long-term survivors of Hodgkin lymphoma survivors treated with high-dose mediastinal radiation therapy (>30 Gy) have progressive decline in cardiopulmonary function and fitness, quantitated by percent-predicted peak Vo₂ (ppVo₂peak) on cardiopulmonary exercise testing. (Left graph) A decline in ppVo₂peak of 7.5 percentage points per 10 years was found. (Right graph) Despite a similar rate of decline between female patients (yellow line) and male patients (blue line), female survivors of Hodgkin lymphoma had lower percent-predicted peak Vo₂ at all follow-up times and a higher frequency of abnormal percent-predicted peak Vo₂. The percent-predicted peak Vo₂ in female patients declined to abnormal levels almost 23 years earlier than in male patients. Light blue shading denotes an abnormal percent-predicted peak Vo₂ region. HR = hazard ratio; MI = myocardial infarction; ↓ = decreased function.