Cardiac Structure Doses in Women Irradiated for Breast Cancer in the Past and Their Use in Epidemiological Studies

Purpose Incidental cardiac exposure during radiation therapy may cause heart disease. Dose-response relationships for cardiac structures (segments) may show which ones are most sensitive to radiation. Radiation-related cardiac injury can take years to develop; thus, studies need to involve women treated using 2-dimensional planning, with segment doses estimated using a typical computed tomography (CT) scan. We assessed whether such segment doses are accurate enough to use in dose-response relationships using the radiation therapy charts of women with known segment injury. We estimated interregimen and interpatient segment dose variability and segment dose correlations. Methods and Materials The radiation therapy charts of 470 women with cardiac segment injury after breast cancer radiation therapy were examined, and 41 regimens were identified. Regimens were reconstructed on a typical CT scan. Doses were estimated for 5 left ventricle (LV) and 10 coronary artery segments. Correlations between cardiac segments were estimated. Interpatient dose variation was assessed in 10 randomly selected CT scans for left regimens and in 5 for right regimens. Results For the typical CT scan, interregimen segment dose variation was substantial (range, LV segments <1-39 Gy; coronary artery segments <1-48 Gy). In 10 CT scans, interpatient segment dose variation was higher for segments near field borders (range, 3-47 Gy) than other segments (range, <2 Gy). Doses to different left-anterior descending coronary artery (LADCA) segments were highly correlated with each other, as were doses to different LV segments. Also, LADCA segment doses were highly correlated with doses to LV segments usually supplied by the LADCA. For individual regimens there was consistency in hotspot location and segment ranking of higher-versus-lower dose. Conclusions The scope for developing quantitative cardiac segment dose-response relationships in patients who had 2-dimensional planning is limited because different segment doses are often highly correlated, and segment-specific dose uncertainties are not independent of each other. However, segment-specific doses may be reliably used to rank segments according to higher-versus-lower doses.

Partially wide tangents (i) (4) 12** 8 MV Breast, IMC 46.0-54.0 1.8-2.0 Superior: 2nd costal cartilage Block defined posterior field border (tapered 1 cm Inferior: 1 cm below inframammary fold around breast tissue below 5th rib) Medial: 3 cm from midline contra Half-beam-blocked superiorly Lateral: mid-axillary line Fixed SSD 100 cm at centre of posterior field edge   Sweden (1958Sweden ( -2001 or Denmark (1978Denmark ( -2000.* Target ( Cobalt chain short (p) 38 C Co 60 C IMC, SCF 7.0-9.0 3.5 C Isocentre 2.5 cm from midline 3.5 cm x 6 cm overlapping fields along the IMC Inferior: 7 cm below 4th intercostal space Cobalt chain (n=74) ¶ ¶ Information was collated from radiotherapy charts, radiotherapy protocols and from oncologists and physicists who had delivered them (see references (i)-(vi) below). ¶Usual total dose (100%) to the target tissues. For direct regimens this was the Dmax. For tangential regimens this was the dose delivered to the centre of the breast/chest wall apart from orthovoltage tangents where the total dose was the skin dose at the surface of the breast. **This includes 3 women irradiated in Sweden whose radiotherapy was similar to this Danish technique. conserving surgery but information was lacking on the location of the surgical bed and heart dose from these fields is likely to be ≤ 1.0 Gy (see Taylor 2007 (vii) ) so these boost fields were not reconstructed.

References
||One woman in the category received 36 Gy in 12 fractions. † †Field size: width (cm) x length (cm). ‡ ‡This includes 7 women irradiated in Sweden whose radiotherapy was similar to this Danish technique. § §This includes 3 Swedish women who received techniques similar to this Danish technique. ¶ ¶For description of cobalt chain see Taylor 2009 (i) .
*Regimens are ordered as in Tables 1,2, and Tables E3,4,7-11. Each technique listed accounts for two regimens, one for left-sided and one for right-sided cancers apart from one direct megavoltage technique (direct bilateral IMC) which was the same for left and rightsided cancers. †Regimens a-p are illustrated in Fig. 1. and Fig. E1. ‡Regimens 1-7 were reconstructed on 10 CT scans to study the effect of paƟent anatomy on segment doses ( Fig. 3-5). §Some regimens included separate fields to the SCF and/or axilla but as the doses to the whole heart and to all of the cardiac structures were less than 0.5 Gy, they were not reconstructed. Some regimens included separate field(s) to boost the surgical bed after breast  (a) and (e) are illustrated in Fig. 1. For regimen (e) the doses reported here are from the direct electron chest wall beam only, not the †Chest wall separaƟon: the distance between the midline and the midaxillary line ‡Haller index: raƟo of height between anterior spine and posterior sternum to the transverse width of the chest. §Scan 5 was selected as the 'average CT dataset' because it was the scan with mean heart doses closest to average from both techniques a and e (which were the two most commonly identified left-sided regimens) and was not atypical for any of the anatomical factors examined. ¶The anatomical factors evaluated did not correlate with mean heart dose and no scan had consistently average readings for these measurements. r= correlation coefficient testing the strength of correlation between mean heart dose and anatomical measurements p= test for correlation equal to zero the lateral photon chest wall field. These regimens are also numbered (3) and (7) (1958 -2001) or Denmark .

Median
Highlighted tangential regimens are wide tangents, others are midline tangents. Highlighted anterior electron or orthovoltage regimens are oblique electron fields, others include direct fields. ‡Regimens a-p are illustrated in Fig. 1  *For further details on the radiotherapy regimens see Table E1.

Anterior electron or orthovoltage
Tangential §Regimens 1-7 were reconstructed on 5 CT scans to study the effect of patient anatomy on segment doses ( Fig. 3-5). Table E4. Mean radiation therapy doses to coronary arterial structures from right-sided breast cancer radiotherapy regimens used in Sweden (1958Sweden ( -2001 or Denmark (1978Denmark ( -2000.

Median
Medial  Fig. 1 and Fig. E1. §Usual total dose (100%) to the target tissues (see Table E1 for dose range). For direct regimens this was the Dmax. For tangential regimens the total dose (100%) was delivered to the centre of the breast or chest wall apart from orthovoltage tangents where the total dose was the skin dose at the surface of the breast. .

Usual beam energy
Left-sided regimens Right-sided regimens

Tangential
Anterior electron or orthovoltage Where there are differences of > 3 Gy between doses estimated by Duane and Taylor i,ii or Lorenzen iii or Thorsen iv , these are highlighted. "-" Regimen not reconstructed *For further details on the radiotherapy regimens see Table E1.
†Mean cardiac doses esƟmated using manual planning i.e. orthovoltage and cobalt chain are given to nearest Gy. Table E8. Mean radiation therapy EQD2 doses to myocardial structures from left-sided breast cancer radiotherapy regimens used in Sweden (1958Sweden ( -2001 or Denmark (1978Denmark ( -2000. Highlighted tangential regimens are wide tangents, others are midline tangents. Highlighted anterior electron or orthovoltage regimens are oblique electron fields, others include direct fields. †EQD2 = nd(d + α/β)/(2 + α/β); EQD2: equivalent dose in 2Gy per fracƟon; n: number of fracƟons; d: dose per fracƟon; α/β: fracƟonaƟon sensiƟvity 2 Gy. ¶Regimens 1-7 were reconstructed on 10 CT scans to study the effect of patient anatomy on segment doses (Fig. 3-5). ||Usual total dose (100%) to the target tissues. For direct regimens this was the Dmax. For tangential regimens this was the dose delivered to the centre of the breast or chest wall apart from orthovoltage tangents where the total dose was the skin dose at the surface of the breast. **EQD2 doses were not estimated for the cardiac substructures because of uncertainties in manual planning. † †EQD2 doses were not calculated as it was not possible to combine the DVH for the orthovoltage field generated using manual planning with the DVH for the megavoltage field generated using CT-planning. *For further details on the radiotherapy regimens see Table E1.

Tangential
Anterior electron or orthovoltage ‡ ‡Cardiac doses are the same for leŌ-sided and right-sided breast cancer as the same field was used for both. ‡Mean cardiac doses esƟmated using manual planning i.e. orthovoltage and cobalt chain are given to nearest Gy. §Regimens a-p are illustrated in Fig. 1 and Fig. E1. Table E9. Mean radiation therapy EQD2 doses to coronary arterial structures from left-sided breast cancer radiotherapy regimens used in Sweden (1958Sweden ( -2001 or Denmark (1978Denmark ( -2000.

Median
Medial Highlighted tangential regimens are wide tangents, others are midline tangents. Highlighted anterior electron or orthovoltage regimens are oblique electron fields, others include direct fields. †EQD2 = nd(d + α/β)/(2 + α/β); EQD2: equivalent dose in 2Gy per fracƟon; n: number of fracƟons; d: dose per fracƟon; α/β: fracƟonaƟon sensiƟvity 2 Gy. §Regimens 1-7 were reconstructed on 10 CT scans to study the effect of patient anatomy on segment doses (Fig. 3-5) ¶Usual total dose (100%) to the target tissues. For direct regimens this was the Dmax. For tangential regimens this was the dose delivered to the centre of the breast or chest wall apart from orthovoltage tangents where the total dose was the skin dose at the surface of the breast. ||EQD2 doses were not estimated for the cardiac substructures because of uncertainties in manual planning. **EQD2 doses were not calculated as it was not possible to combine the DVH for the orthovoltage field generated using manual planning with the DVH for the megavoltage field generated using CT-planning. left anterior descending right *For further details on the radiotherapy regimens see Table E1. ‡Regimens a-p are illustrated in Fig. 1 Table E10. Mean radiation therapy EQD2 doses to myocardial structures from right-sided breast cancer radiotherapy regimens used in Sweden (1958-2001) or Denmark (1978-2000.

Median
Medial Highlighted tangential regimens are wide tangents, others are midline tangents. Highlighted anterior electron or orthovoltage regimens are oblique electron fields, others include direct fields. †EQD2 = nd(d + α/β)/(2 + α/β); EQD2: equivalent dose in 2Gy per fracƟon; n: number of fracƟons; d: dose per fracƟon; α/β: fracƟonaƟon sensiƟvity 2 Gy. ¶Regimens 1-7 were reconstructed on 10 CT scans to study the effect of patient anatomy on segment doses (Fig. 3-5). ||Usual total dose (100%) to the target tissues. For direct regimens this was the Dmax. For tangential regimens this was the dose delivered to the centre of the breast or chest wall apart from orthovoltage tangents where the total dose was the skin dose at the surface of the breast. **EQD2 doses were not estimated for the cardiac substructures because of uncertainties in manual planning. † †EQD2 doses were not calculated as it was not possible to combine the DVH for the orthovoltage field generated using manual planning with the DVH for the megavoltage field generated using CT-planning.

Tangential
Anterior electron or orthovoltage *For further details on the radiotherapy regimens see Table E1. ‡Mean cardiac doses esƟmated using manual planning i.e. orthovoltage and cobalt chain are given to nearest Gy. ‡ ‡Cardiac doses are the same for leŌ-sided and right-sided breast cancer as the same field was used for both. §Regimens a-p are illustrated in Fig. 1 and Fig. E1. Table E11. Mean radiation therapy EQD2 doses to coronary arterial structures from right-sided breast cancer radiotherapy regimens used in Sweden (1958Sweden ( -2001 or Denmark (1978Denmark ( -2000. Highlighted tangential regimens are wide tangents, others are midline tangents. Highlighted anterior electron or orthovoltage regimens are oblique electron fields, others include direct fields. †EQD2 = nd(d + α/β)/(2 + α/β); EQD2: equivalent dose in 2Gy per fracƟon; n: number of fracƟons; d: dose per fracƟon; α/β: fracƟonaƟon sensiƟvity 2 Gy. §Regimens 1-7 were reconstructed on 10 CT scans to study the effect of patient anatomy on segment doses (Fig. 3-5) ¶Usual total dose (100%) to the target tissues. For direct regimens this was the Dmax. For tangential regimens this was the dose delivered to the centre of the breast or chest wall apart from orthovoltage tangents where the total dose was the skin dose at the surface of the breast. ||EQD2 doses were not estimated for the cardiac substructures because of uncertainties in manual planning. **EQD2 doses were not calculated as it was not possible to combine the DVH for the orthovoltage field generated using manual planning with the DVH for the megavoltage field generated using CT-planning.

Tangential
Anterior electron or orthovoltage *For further details on the radiotherapy regimens see Table E1. ‡Regimens a-p are illustrated in Fig. 1 and Fig. E1. † †Cardiac doses are the same for leŌ-sided and right-sided breast cancer as the same field was used for both.