Lung-Heart Outcomes and Mortality through the 2020 COVID-19 Pandemic in a Prospective Cohort of Breast Cancer Radiotherapy Patients

Abstract

We investigated lung-heart toxicity and mortality in 123 women with stage I-II breast cancer enrolled in 2007-2011 in a prospective trial of adjuvant radiotherapy (TomoBreast). We were concerned whether the COVID-19 pandemic affected the outcomes. All patients were analyzed as a single cohort. Lung-heart status was reverse-scored as freedom from adverse-events (fAE) on a 1-5 scale. Left ventricular ejection fraction (LVEF) and pulmonary function tests were untransformed. Statistical analyses applied least-square regression to calendar-year aggregated data. The significance of outliers was determined using the Dixon and the Grubbs corrected tests. At 12.0 years median follow-up, 103 patients remained alive; 10-years overall survival was 87.8%. In 2007-2019, 15 patients died, of whom 11 were cancer-related deaths. In 2020, five patients died, none of whom from cancer. fAE and lung-heart function declined gradually over a decade through 2019, but deteriorated markedly in 2020: fAE dipped significantly from 4.6-4.6 to 4.3-4.2; LVEF dipped to 58.4% versus the expected 60.3% (PDixon = 0.021, PGrubbs = 0.054); forced vital capacity dipped to 2.4 L vs. 2.6 L (PDixon = 0.043, PGrubbs = 0.181); carbon-monoxide diffusing capacity dipped to 12.6 mL/min/mmHg vs. 15.2 (PDixon = 0.008, PGrubbs = 0.006). In conclusion, excess non-cancer mortality was observed in 2020. Deaths in that year totaled one-third of the deaths in the previous decade, and revealed observable lung-heart deterioration.

Keywords: COVID-19; adjuvant radiotherapy; aging; cohort monitoring; hybrid prospective-retrospective study; longitudinal analysis; outlier’s test; pulmonary function test.

Figure 1

Rates of heart and lung toxicity grades over the calendar years. G0, no toxicity. G1–G4, toxicity Grade 1–4. Open circle: rate averaged on all patients observed in the year. Filled circle: rate observed in 2020, year of the COVID pandemic. Line: ordinary least squares fitted on years 2009–2021 excluding 2020. Grey band: 95% confidence interval of the least squares fit.

Figure 2

The effect by year on heart and lung toxicity-free scores. Continuous toxicity-free score scaled from 1 (worst, no freedom from toxicity) to 5 (best, fully free of toxicity), where score = (5—Grade). Open circle: score averaged on all patients observed in the year. Filled circle: score observed in 2020, year of the COVID pandemic. Line: ordinary least squares fitted on years 2009–2021 excluding 2020. Grey band: 95% confidence interval of the least squares fit.

Figure 3

The effect by year on heart and lung function. Open circle: value of the function averaged on all patients observed in the year. Filled circle: value observed in 2020, year of the COVID pandemic. Line: ordinary least squares fitted on years 2009–2021 excluding 2020. Grey band: 95% confidence interval of the least squares fit. The slopes per year are: Left ventricular ejection fraction (%) −0.29; Forced vital capacity (L) −0.063 (=63 mL); Residual volume (L) +0.052 (=52 mL); carbon-monoxide (CO) diffusing capacity (ml/min/mmHg) −0.29.

Figure 4

Overall survival and breast cancer specific survival of the study population.