Associations between treatment and HF risk
| . | Cases (total: 91) . | Controls (total: 278) . | . | . | . | ||
|---|---|---|---|---|---|---|---|
| Treatment factor . | N . | % . | N . | % . | RR* . | 95% CI . | Ptrend† . |
| Radiotherapy | |||||||
| No RT to mediastinum or PAO | 7 | 7.7 | 33 | 11.9 | 1.00 | 0.40-2.50 | |
| PAO-RT, no mediastinal RT | 2 | 2.2 | 16 | 5.8 | 0.66 | 0.15-2.98 | |
| Mediastinal RT, no PAO-RT | 39 | 42.9 | 126 | 45.3 | 1.87 | 1.27-2.75 | |
| Mediastinal RT and PAO-RT | 43 | 47.2 | 103 | 37.0 | 2.59 | 1.80-3.72 | .020 |
| Prescribed mediastinal dose | |||||||
| Average (SD) | 32.7 | (12.2) | 29.8 | (14.6) | |||
| Median (IQR) | 37 | (32-40) | 36 | (30-40) | |||
| 0 Gy (no mediastinal RT) | 9 | 9.9 | 49 | 17.6 | 1.00 | 0.45-2.23 | |
| 20-34 Gy (median 32 Gy) | 15 | 16.5 | 45 | 16.2 | 2.35 | 0.85-6.46 | |
| 35-39 Gy (median 36 Gy) | 34 | 37.4 | 113 | 40.7 | 2.10 | 0.86-5.13 | |
| ≥40 Gy (median 40 Gy) | 33 | 36.3 | 71 | 25.5 | 3.02 | 1.23-7.40 | .027 |
| MHD | |||||||
| Average (SD) | 23.2 | (9.6) | 20.1 | (10.0) | |||
| Median (IQR) | 25.8 | (18.8-30.0) | 22.5 | (16.7-27.2) | |||
| 0 Gy | 7 | 7.7 | 29 | 10.4 | 1.00 | 0.39-2.55 | |
| 1-20 Gy (median 16 Gy) | 21 | 22.2 | 70 | 24.4 | 1.43 | 0.83-2.50 | |
| 21-25 Gy (median 23 Gy) | 20 | 22.2 | 102 | 37.1 | 1.03 | 0.63-1.67 | |
| 26-30 Gy (median 28 Gy) | 27 | 30.0 | 57 | 20.7 | 2.78 | 1.69-4.59 | |
| ≥31 Gy (median 33 Gy) | 16 | 17.8 | 20 | 7.3 | 4.16 | 2.14-8.10 | .002‡ |
| Mean dose to the left ventricle (MLVD) | |||||||
| Average (SD) | 16.7 | (8.8) | 13.8 | (7.9) | |||
| Median (IQR) | 16.5 | (11.9-21.9) | 15.1 | (8.4-19.1) | |||
| 0 Gy | 7 | 7.7 | 29 | 10.4 | 1.00 | 0.39-2.55 | |
| 1-15 Gy (median 13 Gy) | 36 | 39.5 | 144 | 51.8 | 1.27 | 0.86-1.89 | |
| 16-20 Gy (median 19 Gy) | 20 | 22.0 | 68 | 24.5 | 1.65 | 0.98-2.77 | |
| 21-25 Gy (median 23 Gy) | 16 | 17.6 | 23 | 8.3 | 3.84 | 1.97-7.47 | |
| ≥26 Gy (median 30 Gy) | 12 | 13.2 | 14 | 5.1 | 4.39 | 2.00-9.65 | <.001‡ |
| V30 for the left ventricle (%)§ | |||||||
| Average (SD) | 40.8 | (24.7) | 33.9 | (23.7) | |||
| Median (IQR) | 42.8 | (24.8-54.7) | 40.1 | (13.1-49.4) | |||
| 0% | 9 | 9.9 | 35 | 12.6 | 1.00 | 0.48-2.10 | |
| 1-24% (median 12%) | 17 | 18.7 | 60 | 21.6 | 0.95 | 0.52-1.71 | |
| 25-49% (median 40%) | 33 | 36.3 | 121 | 43.5 | 1.05 | 0.70-1.58 | |
| 50-74% (median 60%) | 23 | 25.3 | 51 | 18.3 | 1.80 | 1.12-2.91 | |
| 75-100% (median 84%) | 9 | 9.9 | 11 | 4.0 | 3.22 | 1.32-7.86 | .021‡ |
| V20 for the left ventricle (%)§ | |||||||
| Average (SD) | 49.2 | (26.3) | 41.6 | (26.4) | |||
| Median (IQR) | 53.2 | (33.3-63.3) | 48.5 | (26.9-57.2) | |||
| 0% | 8 | 8.8 | 32 | 11.5 | 1.00 | 0.45-2.23 | |
| 1-24% (median 5%) | 4 | 4.4 | 33 | 11.9 | 0.27 | 0.06-1.11 | |
| 25-49% (median 39%) | 28 | 30.7 | 87 | 31.3 | 1.38 | 0.89-2.14 | |
| 50-74% (median 58%) | 35 | 38.5 | 98 | 35.3 | 1.51 | 0.99-2.28 | |
| 75-100% (median 86%) | 16 | 17.6 | 28 | 10.1 | 2.50 | 1.33-4.69 | .006‡ |
| Chemotherapy | |||||||
| No chemotherapy | 23 | 25.3 | 82 | 29.5 | 1.00 | 0.65-1.55 | |
| CT, but no anthracyclines | 37 | 40.6 | 137 | 49.3 | 0.93 | 0.63-1.37 | |
| CT with anthracyclines | 31 | 64.1 | 59 | 21.2 | 2.83 | 1.43-5.59 | .043 |
| Cumulative anthracycline dose‖ | |||||||
| 0 mg/m2 | 60 | 65.9 | 219 | 78.8 | 1.00 | 0.57-1.74 | |
| <280 mg/m2 (median 210 mg/m2) | 7 | 7.7 | 12 | 4.3 | 2.99 | 1.05-8.50 | |
| ≥280 mg/m2 (median 300 mg/m2)¶ | 24 | 26.4 | 47 | 16.9 | 2.93 | 1.30-6.59 | .006# |
| Salvage therapy | |||||||
| PT: mediastinal RT, no anthra; ST: none or no anthra | 51 | 56.0 | 170 | 61.2 | 1.00 | 0.67-1.47 | |
| PT: mediastinal RT, anthra; ST: none or no anthra | 13 | 14.3 | 31 | 11.2 | 2.30 | 1.02-5.21 | |
| PT: mediastinal RT, no anthra; ST: anthra | 12 | 13.2 | 14 | 5.0 | 3.85 | 1.59-9.36 | |
| Other** | 15 | 16.5 | 63 | 22.7 | 0.59 | 0.31-1.14 | |
| Splenectomy | |||||||
| No | 60 | 66.7 | 176 | 63.8 | 1 | ref | |
| Yes | 30 | 33.3 | 100 | 36.2 | 0.85 | 0.49-1.45 | .54 |
| Unknown | 1 | 1.1 | 2 | 0.7 | — | — | |
| . | Cases (total: 91) . | Controls (total: 278) . | . | . | . | ||
|---|---|---|---|---|---|---|---|
| Treatment factor . | N . | % . | N . | % . | RR* . | 95% CI . | Ptrend† . |
| Radiotherapy | |||||||
| No RT to mediastinum or PAO | 7 | 7.7 | 33 | 11.9 | 1.00 | 0.40-2.50 | |
| PAO-RT, no mediastinal RT | 2 | 2.2 | 16 | 5.8 | 0.66 | 0.15-2.98 | |
| Mediastinal RT, no PAO-RT | 39 | 42.9 | 126 | 45.3 | 1.87 | 1.27-2.75 | |
| Mediastinal RT and PAO-RT | 43 | 47.2 | 103 | 37.0 | 2.59 | 1.80-3.72 | .020 |
| Prescribed mediastinal dose | |||||||
| Average (SD) | 32.7 | (12.2) | 29.8 | (14.6) | |||
| Median (IQR) | 37 | (32-40) | 36 | (30-40) | |||
| 0 Gy (no mediastinal RT) | 9 | 9.9 | 49 | 17.6 | 1.00 | 0.45-2.23 | |
| 20-34 Gy (median 32 Gy) | 15 | 16.5 | 45 | 16.2 | 2.35 | 0.85-6.46 | |
| 35-39 Gy (median 36 Gy) | 34 | 37.4 | 113 | 40.7 | 2.10 | 0.86-5.13 | |
| ≥40 Gy (median 40 Gy) | 33 | 36.3 | 71 | 25.5 | 3.02 | 1.23-7.40 | .027 |
| MHD | |||||||
| Average (SD) | 23.2 | (9.6) | 20.1 | (10.0) | |||
| Median (IQR) | 25.8 | (18.8-30.0) | 22.5 | (16.7-27.2) | |||
| 0 Gy | 7 | 7.7 | 29 | 10.4 | 1.00 | 0.39-2.55 | |
| 1-20 Gy (median 16 Gy) | 21 | 22.2 | 70 | 24.4 | 1.43 | 0.83-2.50 | |
| 21-25 Gy (median 23 Gy) | 20 | 22.2 | 102 | 37.1 | 1.03 | 0.63-1.67 | |
| 26-30 Gy (median 28 Gy) | 27 | 30.0 | 57 | 20.7 | 2.78 | 1.69-4.59 | |
| ≥31 Gy (median 33 Gy) | 16 | 17.8 | 20 | 7.3 | 4.16 | 2.14-8.10 | .002‡ |
| Mean dose to the left ventricle (MLVD) | |||||||
| Average (SD) | 16.7 | (8.8) | 13.8 | (7.9) | |||
| Median (IQR) | 16.5 | (11.9-21.9) | 15.1 | (8.4-19.1) | |||
| 0 Gy | 7 | 7.7 | 29 | 10.4 | 1.00 | 0.39-2.55 | |
| 1-15 Gy (median 13 Gy) | 36 | 39.5 | 144 | 51.8 | 1.27 | 0.86-1.89 | |
| 16-20 Gy (median 19 Gy) | 20 | 22.0 | 68 | 24.5 | 1.65 | 0.98-2.77 | |
| 21-25 Gy (median 23 Gy) | 16 | 17.6 | 23 | 8.3 | 3.84 | 1.97-7.47 | |
| ≥26 Gy (median 30 Gy) | 12 | 13.2 | 14 | 5.1 | 4.39 | 2.00-9.65 | <.001‡ |
| V30 for the left ventricle (%)§ | |||||||
| Average (SD) | 40.8 | (24.7) | 33.9 | (23.7) | |||
| Median (IQR) | 42.8 | (24.8-54.7) | 40.1 | (13.1-49.4) | |||
| 0% | 9 | 9.9 | 35 | 12.6 | 1.00 | 0.48-2.10 | |
| 1-24% (median 12%) | 17 | 18.7 | 60 | 21.6 | 0.95 | 0.52-1.71 | |
| 25-49% (median 40%) | 33 | 36.3 | 121 | 43.5 | 1.05 | 0.70-1.58 | |
| 50-74% (median 60%) | 23 | 25.3 | 51 | 18.3 | 1.80 | 1.12-2.91 | |
| 75-100% (median 84%) | 9 | 9.9 | 11 | 4.0 | 3.22 | 1.32-7.86 | .021‡ |
| V20 for the left ventricle (%)§ | |||||||
| Average (SD) | 49.2 | (26.3) | 41.6 | (26.4) | |||
| Median (IQR) | 53.2 | (33.3-63.3) | 48.5 | (26.9-57.2) | |||
| 0% | 8 | 8.8 | 32 | 11.5 | 1.00 | 0.45-2.23 | |
| 1-24% (median 5%) | 4 | 4.4 | 33 | 11.9 | 0.27 | 0.06-1.11 | |
| 25-49% (median 39%) | 28 | 30.7 | 87 | 31.3 | 1.38 | 0.89-2.14 | |
| 50-74% (median 58%) | 35 | 38.5 | 98 | 35.3 | 1.51 | 0.99-2.28 | |
| 75-100% (median 86%) | 16 | 17.6 | 28 | 10.1 | 2.50 | 1.33-4.69 | .006‡ |
| Chemotherapy | |||||||
| No chemotherapy | 23 | 25.3 | 82 | 29.5 | 1.00 | 0.65-1.55 | |
| CT, but no anthracyclines | 37 | 40.6 | 137 | 49.3 | 0.93 | 0.63-1.37 | |
| CT with anthracyclines | 31 | 64.1 | 59 | 21.2 | 2.83 | 1.43-5.59 | .043 |
| Cumulative anthracycline dose‖ | |||||||
| 0 mg/m2 | 60 | 65.9 | 219 | 78.8 | 1.00 | 0.57-1.74 | |
| <280 mg/m2 (median 210 mg/m2) | 7 | 7.7 | 12 | 4.3 | 2.99 | 1.05-8.50 | |
| ≥280 mg/m2 (median 300 mg/m2)¶ | 24 | 26.4 | 47 | 16.9 | 2.93 | 1.30-6.59 | .006# |
| Salvage therapy | |||||||
| PT: mediastinal RT, no anthra; ST: none or no anthra | 51 | 56.0 | 170 | 61.2 | 1.00 | 0.67-1.47 | |
| PT: mediastinal RT, anthra; ST: none or no anthra | 13 | 14.3 | 31 | 11.2 | 2.30 | 1.02-5.21 | |
| PT: mediastinal RT, no anthra; ST: anthra | 12 | 13.2 | 14 | 5.0 | 3.85 | 1.59-9.36 | |
| Other** | 15 | 16.5 | 63 | 22.7 | 0.59 | 0.31-1.14 | |
| Splenectomy | |||||||
| No | 60 | 66.7 | 176 | 63.8 | 1 | ref | |
| Yes | 30 | 33.3 | 100 | 36.2 | 0.85 | 0.49-1.45 | .54 |
| Unknown | 1 | 1.1 | 2 | 0.7 | — | — | |
MHDs and MLVDs are EQD2 Gy (see “Methods”). Treatment variables include both primary and salvage treatment.
anthra, anthracyclines; CT, chemotherapy; PAO, paraaortic; PT, primary therapy; RT, radiotherapy; SD, standard deviation; ST, salvage therapy.
RRs were estimated conditionally on the matched sets.
Trend test based on median value of the treatment factor in each category.
Ptrend after adjusting for treatment with anthracyclines: MHD < .001; mean dose to the left ventricle, .001; V30 of the left ventricle, 0.034; V20 of the left ventricle, .006.
V30 and V20 are the percentages of the left ventricle volume that received at least 30 and 20 Gy, respectively.
Six cycles of MOPP-ABV hybrid contain 210 mg/m2 anthracycline (35 mg/m2 per cycle); 6 cycles of ABVD contain 300 mg/m2 anthracycline (50 mg/m2 per cycle). There was no significant difference between the HF rate in the 2 dose categories <280 mg/m2 and ≥280 mg/m2 (P = .97).
Most patients who received anthracyclines received either 6 ABVD (prescribed anthracycline dose 300 mg/m2) or 8 MOPP-ABV hybrid (prescribed anthracycline dose 280 mg/m2).
Ptrend after adjusting for MHD, .011; after adjusting for mean dose to the left ventricle, .015.
Includes mainly patients who did not receive mediastinal RT at all, or received mediastinal RT only for salvage treatment, or received anthracyclines for both primary and salvage treatment.